Filed of the Invention The present invention relates to pyrazol [1, 5-a] pyrimidine compounds useful, as protein kinase inhibitors (such as for example, the inhibitors of the cyclin-dependent kinases, mitogen-activated protein kinase (MAPK/ERK), glycogen synthase kinase 3 (GSK3beta) and the like), pharmaceutical compositions containing the compounds, and methods of treatment using the compounds and compositions to treat diseases such as, for example, cancer, inflammation, arthritis, viral diseases, neurodegenerative diseases such as Alzheimer's disease, cardiovascular diseases, and fungal diseases. This application claims benefit of priority from U. S. provisional patent applications, Serial No. 60/408,027 filed September 4,2002, and Serial No. 60/421,959 filed October 29,2002.

Background of the Invention Protein kinase inhibitors include kinases such as, for example, the inhibitors of the cyclin-dependent kinases (CDKs), mitogen activated protein kinase (MAPK/ERK), glycogen synthase kinase 3 (GSK3beta), and the like.

Protein kinase inhibitors are described, for example, by M. Hale et al in W002/22610 A1 and by Y. Mettey et al in J. Med. Chem., (2003) 46 222-236.

The cyclin-dependent kinases are serine/threonine protein kinases, which are the driving force behind the cell cycle and cell proliferation. Individual CDK's, such as, CDK1, CDK2, CDK3, CDK4, CDK5, CDK6 and CDK7, CDK8 and the like, perform distinct roles in cell cycle progression and can be classified as either G1, S, or G2M phase enzymes. Uncontrolled proliferation is a hallmark of cancer cells, and misregulation of CDK function occurs with high frequency in many

important solid tumors. CDK2 and CDK4 are of particular interest because their activities are frequently misregulated in a wide variety of human cancers. CDK2 activity is required for progression through G1 to the S phase of the cell cycle, and CDK2 is one of the key components of the G1 checkpoint. Checkpoints serve to maintain the proper sequence of cell cycle events and allow the cell to respond to insults or to proliferative signals, while the loss of proper checkpoint control in cancer cells contributes to tumorgenesis. The CDK2 pathway influences tumorgenesis at the level of tumor suppressor function (e. g. p52, RB, and p27) and oncogene activation (cyclin E). Many reports have demonstrated that both the coactivator, cyclin E, and the inhibitor, p27, of CDK2 are either over - or underexpressed, respectively, in breast, colon, nonsmall cell lung, gastric, prostate, bladder, non-Hodgkin's lymphom, ovarian, and other cancers. Their altered expression has been shown to correlate with increased CDK2 activity levels and poor overall survival. This observation makes CDK2 and its regulator pathways compelling targets for the development years, a number of adenosine 5'-triphosphate (ATP) competitive small organic molecules as well as peptides have been reported in the literature as CDK inhibitors for the potential treatment of cancers. U. S. 6,413, 974, col. 1, line 23-col. 15, line 10 offers a good description of the various CDKs and their relationship to various types of cancer.

CDK inhibitors are known. For example, flavopiridol (Formula I) is a nonselective CDK inhibitor that is currently undergoing human clinical trials, A. M.

Sanderowicz et al, J. Clin. Oncol. (1998) 16,2986-2999.

Formula I.

Other known inhibitors of the CDKs include, for example, olomoucine (J.

Vesely et al, Eur. J. Biochem., (1994) 224, 771-786) and roscovitine (I. Meijer et al, Eur. J. Biochem., (1997) 243,527-536). U. S. 6,107, 305 describes certain pyrazol [3,4-b] pyridine compounds as CDK inhibitors. An illustrative compound from the'305 patent has the Formula ll : Formula II K. S. Kim et al, J. Med. Chem. 45 (2002) 3905-3927 and WO 02/10162 disclose certain aminothiazole compounds as CDK inhibitors.

Pyrazolopyrimidines are known. For Example, W092/18504, W002/50079, W095/35298, W002/40485, EP94304104.6, EP0628559 (equivalent to US Patents 5,602, 136,5, 602,137 and 5,571, 813), U. S. 6,383, 790, Chem. Pharm. Bull., (1999) 47 928, J. Med. Chem. , (1977) 20,296, J. Med.

Chem., (1976) 19 517 and Chem. Pharm. Bull., (1962) 10 620 disclose various pyrazolopyrimidines. Other publications of interest are: WO 03/101993 (published December 11,2003), WO 03/091256 (published November 6,2003), and DE 10223917 (published December 11,2003).

There is a need for new compounds, formulations, treatments and therapies to treat diseases and disorders associated with CDKs. It is, therefore, an object of this invention to provide compounds useful in the treatment or prevention or amelioration of such diseases and disorders.

Summary of the invention In its many embodiments, the present invention provides a novel class of pyrazol [1, 5-a) pyrimidine compounds as inhibitors of cyclin dependent kinases, methods of preparing such compounds, pharmaceutical compositions comprising one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition or amelioration of one or more diseases associated with the CDKs using such compounds or pharmaceutical compositions.

In one aspect, the present application discloses a compound, or pharmaceutical acceptable salts or solvates of said compound, said compound having the general structure shown in Formula III : Formula III wherein: R is H, alkyl, alkenyl, alkynyl, arylalkyl, arylalkenyl, cycloalkyl, cycloalkylalkyl, alkenylalkyl, alkynylalkyl, heterocyclyl, heterocyclylalkyl, heteroarylalkyl (including N-oxide of said heteroaryl),- (CHRS) n-aryl,- (CHR5) n- , (CHR5) v s . heteroary), 1-2, ? > > (CHRS) N-R8 (CHRS) N (CHRS) ri N O J,, or (CHRS) N 0 p wherein each of said alkyl, alkenyl, aikynyi, aryl, cycloalkyl, heterocyclyl, and heteroaryl can be unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being independently

selected from the group consisting of halogen, alkyl, aryl, cycloalkyl, heterocyclylalkyl, CF3, OCF3, CN, -OR5, -NR5R10, -C(R4R5)P-R9, -N(R5)Boc, -(CR4R5)pOR5, -C(O2)R5, -C(O)R5, -C(O)NR5R10, -SO3H, -SR10, - S (02) R7,-S (02) NR5R°,-N (R5) S (02) R7,-N (R5) C (O) R7 and-N (R5) C (O) NR5R10 ; R2 is selected from the group consisting of R9, alkyl, alkenyl, alkynyl, CF3, heterocyclyl, heterocyclylalkyl, halogen, haloalkyl, aryl, arylalkyl, heteroarylalkyl, alkynylalkyl, cycloalkyl, heteroaryl, alkyl substituted with 1-6 R9 groups which can be the same or different and are independently selected from the list of R9 shown below, aryl substituted with 1-3 aryl or heteroaryl groups which can be the same or different and are independently selected from phenyl, pyridyl, thiophenyl, furanyl and thiazolo groups, aryl fused with an aryl or heteroaryl group, heteroaryl substituted with 1-3 aryl or heteroaryl groups which can be the same or different and are independently selected from phenyl, pyridyl, thiophenyl, furanyl and thiazolo groups, heteroaryl fused with an aryl or - (CH2) n-N N-RS heteroaryl group,, ce \ CN-R8 g aryl N<NR8 8 arylCN_Rs , ---and , wherein one or more of the aryl and/or one or more of the heteroaryl in the above-noted definitions for R2 can be unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halogen,-CN,-OR5,-SR5, -S(O2)R6, -S(O2)NR5R6, -NR5R6, -C(O)NR5R6, CF3, alkyl, aryl and OCF3 ; is selected from the group consisting of H, halogen, -NR5R6, -OR6, - SR6,-C (O) N (R5R6), alkyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl and heteroarylalkyl,

wherein each of said alkyl, cycloalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl and heteroarylalkyl for R3 and the heterocyclyl moieties whose structures are shown immediately above for R3 can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halogen, alkyl, aryl, cycloalkyl, CF3, CN,-OCF3, -(CR4R5)pOR5, -OR5, -NR5R6, -(CR4R5)pNR5R6, -C(O2)R5, -C(O)R5, -C(O)NR5R6, -SR6, -S(O2)R6, -S(O2)NR5R6, -N(R5)S(O2)R7, -N(R5)C(O)R7 and -N(R5) C (O) NR5R6, with the proviso that no carbon adjacent to a nitrogen atom on a heterocyclyl ring carries a-OR5 moiety; R4is H, halo or alkyl ; R5is H, alkyl, aryl or cycloalkyl ; R6 is selected from the group consisting of H, alkyl, alkenyl, aryl, arylalkyl, arylalkenyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl, wherein each of said alkyl, aryl, arylalkyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl can be unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halogen, alkyl, aryl, cycloalkyl, heterocyclylalkyl, CF3, OCF3, CN,-OR5,-NRSR'o, -C(R4R5)p-R9, -N(R5)Boc, -(CR4R5)pOR5, -C(O2)R5, -C(O)R5, -C(O)NR5R10, -SO3H, -SR10, -S(O2)R7, -S (02) NR5R10, -N(R5) S (02) R7,-N (R5) C (O) R7 and -N (R5) C (O) NR5R10 ; Rlo is selected from the group consisting of H, alkyl, aryl, arylalkyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl, wherein each of said alkyl, aryl, arylalkyl, cycloalkyl, heterocyclyl,

heterocyclylalkyl, heteroaryl, and heteroarylalkyl can be unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halogen, alkyl, aryl, cycloalkyl, heterocyclylalkyl, CF3, OCF3, CN,-OR5,-NR4R5, -C(R4R5)p-R9, -N(R5)Boc, -(CR4R5)pOR5, -C(O2)R5, -C(O)NR4R5, -C(O)R5, -SO2H, -SR5, -S(O2)R7, -S(O2)NR4R5, -N(R5) S (02) R7,-N (R5) C (O) R7 and -N(R5) C (O) NR4R5 ; or optionally (i) R5 and R10 in the moiety -NR5R10, or (ii) R5 and R6 in the moiety-NR5R6, may be joined together to form a cycloalkyl or heterocyclyl moiety, with each of said cycloalkyl or heterocyclyl moiety being unsubstituted or optionally independently being substituted with one or more R9 groups; R7 is selected from the group consisting of alkyl, cycloalkyl, aryl, arylalkenyl, heteroaryl, arylalkyl, heteroarylalkyl, heteroarylalkenyl, and heterocyclyl, wherein each of said alkyl, cycloalkyl, heteroarylalkyl, aryl, heteroaryl and arylalkyl can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halogen, alkyl, aryl, cycloalkyl, CF3, OCF3, CN, -OR5, -NR5R10, -CH2OR5, -C(O2)R5, -C(O)NR5R10, -C(O)R5, -SR10, -S(O2)R10, -S(O2)NR5R10, -N(R5)S(O2)R10, -N(R5)C(O)R10 and-N (R5) C (O) NR ; R 8 is selected from the group consisting of R6, -OR6, -C(O)NR5R10, <BR> <BR> -S(O2)NR5R10, -C(O)R7, -C (=N-CN) -NH2,-C (=NH)-NHR5, heterocyclyl, and<BR> <BR> <BR> <BR> - S02) R'; R9 is selected from the group consisting of halogen, -CN, -NR5R10, - C(O2)R6, -C(O)NR5R10, -OR6, -SR6, -S(O2)R7, -S(O2)NR5R10, -N(R5) S (02) R7, -N(R5) C (O) R7and-N (R5) C (O) NR5R10; m is 0 to 4; n is 1 to 4; and pis1 to4, with the proviso that when R2 is phenyl, R3 is not alkyl, alkynyl or halogen, and that when R2 is aryl, and with the further proviso

that when R is arylalkyl, then any heteroaryl substituent on the aryl of said arylalkyl contains at least three heteroatoms.

The compounds of Formula III can be useful as protein kinase inhibitors and can be useful in the treatment and prevention of proliferative diseases, for example, cancer, inflammation and arthritis. They may also be useful in the treatment of neurodegenerative diseases such Alzheimer's disease, cardiovascular diseases, viral diseases and fungal diseases.

Detailed Description In one embodiment, the present invention discloses pyrazol [1,5- a) pyrimidine compounds which are represented by structural Formula lil, or a pharmaceutically acceptable salt or solvate thereof, wherein the various moieties are as described above.

In another embodiment, R is- n-aryl,-(CHR5) n-heteroaryl, - (CHR5) n-heteroaryl (with said heteroaryl being substituted with an additional, same or different, heteroaryl),- (CHR5) n-heterocyclyl (with said heterocyclyl being substituted with an additional, same or different, heterocyclyl), or In another embodiment, R2 is halogen, CF3, CN, lower alkyl, alkyl substituted with-OR6, alkynyl, aryl, heteroaryl or heterocyclyl.

In another embodiment, R3 is H, lower alkyl, aryl, heteroaryl, cycloalkyl, NR5R6

wherein said alkyl, aryl, heteroaryl, cycloalkyl and the heterocyclyl structures shown immediately above for R3 are optionally substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halogen, CF3, OCF3, lower alkyl, CN, - C (O) R5,-S (02) R5,-C (=NH) -NH2, -C (=CN)-NH2, hydroxyalkyl, alkoxycarbonyl, -SR5, and OR, with the proviso that no carbon adjacent to a nitrogen atom on a heterocyclyl ring carries a-OR5 moiety.

In another embodiment, R4 is H or lower alkyl.

In another embodiment, R5 is H, lower alkyl or cycloalkyl.

In another embodiment, n is 1 to 2.

In an additional embodiment, R is-(CHR5) n-aryl,-(CHR5) n-heteroaryl.

In an additional embodiment, R2 is halogen, CF3, CN, lower alkyl, alkynyl, or alkyl substituted with-OR6.

In an additional embodiment, R2 is lower alkyl, alkynyl or Br.

In an additional embodiment, R3 is H, lower alkyl, aryl, wherein said alkyl, aryl and the heterocyclyl moieties shown immediately above for R3 are optionally substituted with one or more moieties which can be the same

or different, each moiety being independently selected from the group consisting of halogen, CF3, lower alkyl, hydroxyalkyl, alkoxy,-S (02) R5, and CN.

In an additional embodiment, R4 is H.

In an additional embodiment, R5 is H, ethyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

In an additional embodiment, R8 is alkyl or hydroxyalkyl.

In an additional embodiment, n is 1.

In an additional embodiment, p is 1 or 2.

Another embodiment discloses the inventive compounds shown in Table 1, which exhibited CDK2 inhibitory activity of about 0.0001 tM to > about 5 µM.

The assay methods are described later (from page 333 onwards).

Table 1

Another embodiment of the invention discloses the following compounds, which exhibited CDK2 inhibitory activity of about 0. 0001 gM to about 0. 5µM :

Another embodiment of the invention discloses the following compounds, which exhibited CDK2 inhibitory activity of about 0. 0001µM to about 0. elm :

As used above, and throughout this disclosure, the following terms, unless otherwise indicated, shall be understood to have the following meanings:

"Patient"includes both human and animals.

"Mammal"means humans and other mammalian animals.

"Alkyl"means an aliphatic hydrocarbon group which may be straight or branched and comprising about 1 to about 20 carbon atoms in the chain.

Preferred alkyl groups contain about 1 to about 12 carbon atoms in the chain.

More preferred alkyl groups contain about 1 to about 6 carbon atoms in the chain. Branched means that one or more lower alkyl groups such as methyl, ethyl or propyl, are attached to a linear alkyl chain. "Lower alkyl"means a group having about 1 to about 6 carbon atoms in the chain which may be straight or branched. The term"substituted alkyl"means that the alkyl group may be substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of halo, alkyl, aryl, cycloalkyl, cyano, hydroxy, alkoxy, alkylthio, amino, -NH (alkyl),- NH (cycloalkyl),-N (alkyl) 2, carboxy and-C (0) 0-alkyl. Non-limiting examples of suitable alkyl groups include methyl, ethyl, n-propyl, isopropyl and t-butyl.

"Alkynyl"means an aliphatic hydrocarbon group containing at least one carbon-carbon triple bond and which may be straight or branched and comprising about 2 to about 15 carbon atoms in the chain. Preferred alkynyl groups have about 2 to about 12 carbon atoms in the chain; and more preferably about 2 to about 4 carbon atoms in the chain. Branched means that one or more lower alkyl groups such as methyl, ethyl or propyl, are attached to a linear alkynyl chain. "Lower alkynyl"means about 2 to about 6 carbon atoms in the chain which may be straight or branched. Non-limiting examples of suitable alkynyl groups include ethynyl, propynyl, 2-butynyl and 3-methylbutynyl. The term"substituted alkynyl"means that the alkynyl group may be substituted by one or more substituents which may be the same or different, each substituent being independently selected from the group consisting of alkyl, aryl and cycloalkyl.

"Aryl"means an aromatic monocyclic or multicyclic ring system comprising about 6 to about 14 carbon atoms, preferably about 6 to about 10 carbon atoms. The aryl group can be optionally substituted with one or more "ring system substituents"which may be the same or different, and are as

defined herein. Non-limiting examples of suitable aryl groups include phenyl and naphthyl.

"Heteroaryl"means an aromatic monocyclic or multicyclic ring system comprising about 5 to about 14 ring atoms, preferably about 5 to about 10 ring atoms, in which one or more of the ring atoms is an element other than carbon, for example nitrogen, oxygen or sulfur, alone or in combination. Preferred heteroaryls contain about 5 to about 6 ring atoms. The"heteroaryl"can be optionally substituted by one or more"ring system substituents"which may be the same or different, and are as defined herein. The prefix aza, oxa or thia before the heteroaryl root name means that at least a nitrogen, oxygen or sulfur atom respectively, is present as a ring atom. A nitrogen atom of a heteroaryl can be optionally oxidized to the corresponding N-oxide. Non-limiting examples of suitable heteroaryls include pyridyl, pyrazinyl, furanyl, thienyl, pyrimidinyl, pyridone (including N-substituted pyridones), isoxazolyl, isothiazolyl, oxazolyl, thiazolyl, pyrazolyl, furazanyl, pyrrolyl, pyrazolyl, triazolyl, 1,2, 4-thiadiazolyl, pyrazinyl, pyridazinyl, quinoxalinyl, phthalazinyl, oxindolyl, imidazo [1,2- a] pyridinyl, imidazo [2,1-b] thiazolyl, benzofurazanyl, indolyl, azaindolyl, benzimidazolyl, benzothienyl, quinolinyl, imidazolyl, thienopyridyl, quinazolinyl, thienopyrimidyl, pyrrolopyridyl, imidazopyridyl, isoquinolinyl, benzoazaindolyl, 1,2, 4-triazinyl, benzothiazolyl and the like. The term"heteroaryl"also refers to partially saturated heteroaryl moieties such as, for example, tetrahydroisoquinolyl, tetrahydroquinolyl and the like.

"Aralkyl"or"arylalkyl"means an aryl-alkyl-group in which the aryl and alkyl are as previously described. Preferred aralkyl comprise a lower alkyl group. Non-limiting examples of suitable aralkyl groups include benzyl, 2- phenethyl and naphthalenylmethyl. The bond to the parent moiety is through the alkyl.

"Alkylaryl"means an alkyl-aryl-group in which the alkyl and aryl are as previously described. Preferred alkylaryl comprise a lower alkyl group. Non- limiting example of a suitable alkylaryl group is tolyl. The bond to the parent moiety is through the aryl...

"Cycloalkyl"means a non-aromatic mono-or multicyclic ring system comprising about 3 to about 10 carbon atoms, preferably about 5 to about 10 carbon atoms. Preferred cycloalkyl rings contain about 5 to about 7 ring atoms.

The cycloalkyl can be optionally substituted with one or more"ring system substituents"which may be the same or different ; and are as defined above.

Non-limiting examples of suitable monocyclic cycloalkyls include cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl and the like. Non-limiting examples of suitable multicyclic cycloalkyls include 1-decalinyl, norbornyl, adamantyl and the like, as well as partially saturated species such as, for example, indanyl, tetrahydronaphthyl and the like.

"Halogen"means fluorine, chlorine, bromine, or iodine. Preferred are fluorine, chlorine and bromine.

"Ring system substituent"means a substituent attached to an aromatic or non-aromatic ring system which, for example, replaces an available hydrogen on the ring system. Ring system substituents may be the same or different, each being independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl, alkylaryl, heteroaralkyl, heteroarylalkenyl, heteroarylalkynyl, alkylheteroaryl, hydroxy, hydroxyalkyl, alkoxy, aryloxy, aralkoxy, acyl, aroyl, halo, nitro, cyano, carboxy, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, alkylthio, arylthio, heteroarylthio, aralkylthio, heteroaralkylthio, cycloalkyl, heterocyclyi,-C (=N-CN) -NH2, -C (=NH) -NH2,-C (=NH)-NH (alkyl), Y1Y2N-, Y1Y2N-alkyl-, Y1Y2NC (O)-, Y1Y2NSO2-and-SO2NY1Y2, wherein Y1 and Y2 can be the same or different and are independently selected from the group consisting of hydrogen, alkyl, aryl, cycloalkyl, and aralkyl."Ring system substituent"may also mean a single moiety which simultaneously replaces two available hydrogens on two adjacent carbon atoms (one H on each carbon) on a ring system. Examples of such moiety are methylene dioxy, ethylenedioxy,- C (CH3) 2- and the like which form moieties such as, for example:

"Heterocyclyl"means a non-aromatic saturated monocyclic or multicyclic ring system comprising about 3 to about 10 ring atoms, preferably about 5 to about 10 ring atoms, in which one or more of the atoms in the ring system is an element other than carbon, for example nitrogen, oxygen or sulfur, alone or in combination. There are no adjacent oxygen and/or sulfur atoms present in the ring system. Preferred heterocyclyls contain about 5 to about 6 ring atoms. The prefix aza, oxa or thia before the heterocyclyl root name means that at least a nitrogen, oxygen or sulfur atom respectively is present as a ring atom. Any-NH in a heterocyclyl ring may exist protected such as, for example, as an-N (Boc),- N (CBz), -N (Tos) group and the like ; such protections are also considered part of this invention. The heterocyclyl can be optionally substituted by one or more "ring system substituents"which may be the same or different, and are as defined herein. The nitrogen or sulfur atom of the heterocyclyl can be optionally oxidized to the corresponding N-oxide, S-oxide or S, S-dioxide. Non-limiting examples of suitable monocyclic heterocyclyl rings include piperidyl, pyrrolidinyl, piperazinyl, morpholinyl, thiomorpholinyl, thiazolidinyl, 1, 4-dioxanyl, tetrahydrofuranyl, tetrahydrothiophenyl, lactam, lactone, and the like.

It should be noted that in hetero-atom containing ring systems of this invention, there are no hydroxyl groups on carbon atoms adjacent to a N, O or S, as well as there are no N or S groups on carbon adjacent to another heteroatom.

Thus, for example, in the ring: there is no-OH attached directly to carbons marked 2 and 5.

It should also be noted that tautomeric forms such as, for example, the moieties: are considered equivalent in certain embodiments of this invention.

"Alkynylalkyl"means an alkynyl-alkyl-group in which the alkynyl and alkyl are as previously described. Preferred alkynylalkyls contain a lower alkynyl and a lower alkyl group. The bond to the parent moiety is through the alkyl. Non- limiting examples of suitable alkynylalkyl groups include propargylmethyl.

"Heteroaralkyl"means a heteroaryl-alkyl-group in which the heteroaryl and alkyl are as previously described. Preferred heteroaralkyls contain a lower alkyl group. Non-limiting examples of suitable aralkyl groups include pyridylmethyl, and quinolin-3-ylmethyl. The bond to the parent moiety is through the alkyl.

"Hydroxyalkyl"means a HO-alkyl-group in which alkyl is as previously defined. Preferred hydroxyalkyls contain lower alkyl. Non-limiting examples of suitable hydroxyalkyl groups include hydroxymethyl and 2-hydroxyethyl.

"Acyl"means an H-C (O)-, alkyl-C (O)- or cycloalkyl-C (O) -, group in which the various groups are as previously described. The bond to the parent moiety is through the carbonyl. Preferred acyls contain a lower alkyl. Non-limiting examples of suitable acyl groups include formyl, acetyl and propanol.

"Aroyl"means an aryl-C (O)- group in which the aryl group is as previously described. The bond to the parent moiety is through the carbonyl. Non-limiting examples of suitable groups include benzoyl and 1-naphthoyl.

"Alkoxy"means an alkyl-O-group in which the alkyl group is as previously described. Non-limiting examples of suitable alkoxy groups include methoxy, ethoxy, n-propoxy, isopropoxy and n-butoxy. The bond to the parent moiety is through the ether oxygen.

"Aryloxy"means an aryl-O-group in which the aryl group is as previously described. Non-limiting examples of suitable aryloxy groups include phenoxy and naphthoxy. The bond to the parent moiety is through the ether oxygen.

"Aralkyloxy"means an aralkyl-O-group in which the aralkyl group is as previously described. Non-limiting examples of suitable aralkyloxy groups include benzyloxy and 1-or 2-naphthalenemethoxy. The bond to the parent moiety is through the ether oxygen.

"Alkylthio"means an alkyl-S-group in which the alkyl group is as previously described. Non-limiting examples of suitable alkylthio groups include methylthio and ethylthio. The bond to the parent moiety is through the sulfur.

"Arylthio"means an aryl-S-group in which the aryl group is as previously described. Non-limiting examples of suitable arylthio groups include phenylthio and naphthylthio. The bond to the parent moiety is through the sulfur.

"Aralkylthio"means an aralkyl-S-group in which the aralkyl group is as previously described. Non-limiting example of a suitable aralkylthio group is benzylthio. The bond to the parent moiety is through the sulfur.

"Alkoxycarbonyl"means an alkyl-O-CO-group. Non-limiting examples of suitable alkoxycarbonyl groups include methoxycarbonyl and ethoxycarbonyl.

The bond to the parent moiety is through the carbonyl.

"Aryloxycarbonyl"means an aryl-O-C (O)- group. Non-limiting examples of suitable aryloxycarbonyl groups include phenoxycarbonyl and naphthoxycarbonyl. The bond to the parent moiety is through the carbonyl.

"Aralkoxycarbonyl"means an aralkyl-O-C (O)-group. Non-limiting example of a suitable aralkoxycarbonyl group is benzyloxycarbonyl. The bond to the parent moiety is through the carbonyl.

"Alkylsulfonyl"means an alkyl-S (02)-group. Preferred groups are those in which the alkyl group is lower alkyl. The bond to the parent moiety is through the sulfonyl.

"Arylsulfonyl"means an aryl-S (02)- group. The bond to the parent moiety is through the sulfonyl.

The term"substituted"means that one or more hydrogens on the designated atom is replaced with a selection from the indicated group, provided that the designated atom's normal valency under the existing circumstances is not exceeded, and that the substitution results in a stable compound.

Combinations of substituents and/or variables are permissible only if such combinations result in stable compounds. By"stable compound'or"stable structure"is meant a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture, and formulation into an efficacious therapeutic agent.

The term"optionally substituted"means optional substitution with the specified groups, radicals or moieties.

The term"isolated"or"in isolated form"for a compound refers to the physical state of said compound after being isolated from a synthetic process or natural source or combination thereof. The term"purified"or"in purified form"for a compound refers to the physical state of said compound after being obtained from a purification process or processes described herein or well known to the skilled artisan, in sufficient purity to be characterizable by standard analytical techniques described herein or well known to the skilled artisan.

It should also be noted that any heteroatom with unsatisfied valences in the text, schemes, examples and Tables herein is assumed to have the hydrogen atom (s) to satisfy the valences.

When a functional group in a compound is termed"protected", this means that the group is in modified form to preclude undesired side reactions at the protected site when the compound is subjected to a reaction. Suitable protecting groups will be recognized by those with ordinary skill in the art as well as by reference to standard textbooks such as, for example, T. W. Greene et a/, Protective Groups in organic Synthesis (1991), Wiley, New York.

When any variable (e. g., aryl, heterocycle, R2, etc. ) occurs more than one time in any constituent or in Formula III, its definition on each occurrence is independent of its definition at every other occurrence.

As used herein, the term"composition"is intended to encompass a product comprising the specified ingredients in the specified amounts, as well as any product which results, directly or indirectly, from combination of the specified ingredients in the specified amounts.

Prodrugs and solvates of the compounds of the invention are also contemplated herein. The term"prodrug", as employed herein, denotes a compound that is a drug precursor which, upon administration to a subject, undergoes chemical conversion by metabolic or chemical processes to yield a compound of Formula III or a salt and/or solvate thereof. A discussion of prodrugs is provided in T. Higuchi and V. Stella, Pro-drugs as Novel Delivery Systems (1987) 14 of the A. C. S. Symposium Series, and in Bioreversible

Carriers in Drug Design, (1987) Edward B. Roche, ed. , American Pharmaceutical Association and Pergamon Press, both of which are incorporated herein by reference thereto.

"Solvate"means a physical association of a compound of this invention with one or more solvent molecules. This physical association involves varying degrees of ionic and covalent bonding, including hydrogen bonding. In certain instances the solvate will be capable of isolation, for example when one or more solvent molecules are incorporated in the crystal lattice of the crystalline solid.

"Solvate"encompasses both solution-phase and isolatable solvates. Non-limiting examples of suitable solvates include ethanolates, methanolates, and the like.

"Hydrate"is a solvate wherein the solvent molecule is H2O.

"Effective amount"or"therapeutically effective amount"is meant to describe an amount of compound or a composition of the present invention effective in inhibiting the CDK (s) and thus producing the desired therapeutic, ameliorative, inhibitory or preventative effect.

The compounds of Formula III can form salts which are also within the scope of this invention. Reference to a compound of Formula III herein is understood to include reference to salts thereof, unless otherwise indicated. The term"salt (s) ", as employed herein, denotes acidic salts formed with inorganic and/or organic acids, as well as basic salts formed with inorganic and/or organic bases. In addition, when a compound of Formula IlI contains both a basic moiety, such as, but not limited to a pyridine or imidazole, and an acidic moiety, such as, but not limited to a carboxylic acid, zwitterions ("inner salts") may be formed and are included within the term"salt (s)" as used herein.

Pharmaceutically acceptable (i. e. , non-toxic, physiologically acceptable) salts are preferred, although other salts are also useful. Salts of the compounds of the Formula III may be formed, for example, by reacting a compound of Formula III with an amount of acid or base, such as an equivalent amount, in a medium such as one in which the salt precipitates or in an aqueous medium followed by lyophilization.

Exemplary acid addition salts include acetates, ascorbates, benzoates, benzenesulfonates, bisulfates, borates, butyrates, citrates, camphorates,

camphorsulfonates, fumarates, hydrochlorides, hydrobromides, hydroiodides, lactates, maleates, methanesulfonates, naphthalenesulfonates, nitrates, oxalates, phosphates, propionates, salicylates, succinates, sulfates, tartarates, thiocyanates, toluenesulfonates (also known as tosylates,) and the like.

Additionally, acids which are generally considered suitable for the formation of pharmaceutical useful salts from basic pharmaceutical compounds are discussed, for example, by S. Berge et al, Journal of Pharmaceutical Sciences (1977) 66 (1) 1-19 ; P. Gould, International J. of Pharmaceutics (1986) 33 201- 217; Anderson et al, The Practice of Medicinal Chemistry (1996), Academic Press, New York; and in The Orange Book (Food & Drug Administration, Washington, D. C. on their website). These disclosures are incorporated herein by reference thereto.

Exemplary basic salts include ammonium salts, alkali metal salts such as sodium, lithium, and potassium salts, alkaline earth metal salts such as calcium and magnesium salts, salts with organic bases (for example, organic amines) such as dicyclohexylamines, t-butyl amines, and salts with amino acids such as arginine, lysine and the like. Basic nitrogen-containing groups may be quarternized with agents such as lower alkyl halides (e. g. methyl, ethyl, and butyl chlorides, bromides and iodides), dialkyl sulfates (e. g. dimethyl, diethyl, and dibutyl sulfates), long chain halides (e. g. decyl, lauryl, and stearyl chlorides, bromides and iodides), aralkyl halides (e. g. benzyl and phenethyl bromides), and others.

All such acid salts and base salts are intended to be pharmaceutically acceptable salts within the scope of the invention and all acid and base salts are considered equivalent to the free forms of the corresponding compounds for purposes of the invention.

Compounds of Formula ! ii, and salts, solvates and prodrugs thereof, may exist in their tautomeric form (for example, as an amide or imino ether). All such tautomeric forms are contemplated herein as part of the present invention.

All stereoisomers (for example, geometric isomers, optical isomers and the like) of the present compounds (including those of the salts, solvates and prodrugs of the compounds as well as the salts and solvates of the prodrugs),

such as those which may exist due to asymmetric carbons on various substituents, including enantiomeric forms (which may exist even in the absence of asymmetric carbons), rotameric forms, atropisomers, and diastereomeric forms, are contemplated within the scope of this invention, as are positional isomers (such as, for example, 4-pyridyl and 3-pyridyl). Individual stereoisomers of the compounds of the invention may, for example, be substantially free of other isomers, or may be admixed, for example, as racemates or with all other, or other selected, stereoisomers. The chiral centers of the present invention can have the S or R configuration as defined by the IUPAC 1974 Recommendations.

The use of the terms"salt","solvate""prodrug"and the like, is intended to equally apply to the salt, solvate and prodrug of enantiomers, stereoisomers, rotamers, tautomers, positional isomers, racemates or prodrugs of the inventive compounds.

The compounds according to the invention have pharmacological properties; in particular, the compounds of Formula III can be inhibitors of protein kinases such as, for example, the inhibitors of the cyclin-dependent kinases, mitogen-activated protein kinase (MAPK/ERK), glycogen synthase kinase 3 (GSK3beta) and the like. The cyclin dependent kinases (CDKs) include, for example, CDC2 (CDK1), CDK2, CDK4, CDK5, CDK6, CDK7 and CDK8. The novel compounds of Formula III are expected to be useful in the therapy of proliferative diseases such as cancer, autoimmune diseases, viral diseases, fungal diseases, neurological/neurodegenerative disorders, arthritis, inflammation, anti-proliferative (e. g., ocular retinopathy), neuronal, alopecia and cardiovascular disease. Many of these diseases and disorders are listed in U. S.

6,413, 974 cited earlier, the disclosure of which is incorporated herein.

More specifically, the compounds of Formula III can be useful in the treatment of a variety of cancers, including (but not limited to) the following: carcinoma, including that of the bladder, breast, colon, kidney, liver, lung, including small cell lung cancer, esophagus, gall bladder, ovary, pancreas, stomach, cervix, thyroid, prostate, and skin, including squamous cell carcinoma; hematopoietic tumors of lymphoid lineage, including leukemia, acute lymphocytic leukemia, acute lymphoblastic leukemia, B-cell lymphom, T-cell

lymphom, Hodgkins lymphom, non-Hodgkins lymphom, hairy cell lymphom and Burkett's lymphom ; hematopoietic tumors of myeloid lineage, including acute and chronic myelogenous leukemias, myelodysplastic syndrome and promyelocytic leukemia ; tumors of mesenchymal origin, including fibrosarcoma and rhabdomyosarcoma; tumors of the central and peripheral nervous system, including astrocytoma, neuroblastoma, glioma and schwannomas; and other tumors, including melanoma, seminoma, teratocarcinoma, osteosarcoma, xenoderoma pigmentosum, keratoctanthoma, thyroid follicular cancer and Kaposi's sarcoma.

Due to the key role of CDKs in the regulation of cellular proliferation in general, inhibitors could act as reversible cytostatic agents which may be useful in the treatment of any disease process which features abnormal cellular proliferation, e. g., benign prostate hyperplasia, familial adenomatosis polyposis, neuro-fibromatosis, atherosclerosis, pulmonary fibrosis, arthritis, psoriasis, glomerulonephritis, restenosis following angioplasty or vascular surgery, hypertrophic scar formation, inflammatory bowel disease, transplantation rejection, endotoxic shock, and fungal infections.

Compounds of Formula III may also be useful in the treatment of Alzheimer's disease, as suggested by the recent finding that CDK5 is involved in the phosphorylation of tau protein (J. Biochem, (1995) 117, 741-749).

Compounds of Formula III may induce or inhibit apoptosis. The apoptotic response is aberrant in a variety of human diseases. Compounds of Formula III, as modulators of apoptosis, will be useful in the treatment of cancer (including but not limited to those types mentioned hereinabove), viral infections (including but not limited to herpevirus, poxvirus, Epstein-Barr virus, Sindbis virus and adenovirus), prevention of AIDS development in HIV-infected individuals, autoimmune diseases (including but not limited to systemic lupus, erythematosus, autoimmune mediated glomerulonephritis, rheumatoid arthritis, psoriasis, inflammatory bowel disease, and autoimmune diabetes mellitus),

neurodegenerative disorders (including but not limited to Alzheimer's disease, AIDS-related dementia, Parkinson's disease, amyotrophic lateral sclerosis, retinitis pigmentosa, spinal muscular atrophy and cerebella degeneration), myelodysplastic syndromes, plastic anemia, ischemic injury associated with myocardial infarctions, stroke and reperfusion injury, arrhythmia, atherosclerosis, toxin-induced or alcohol related liver diseases, hematological diseases (including but not limited to chronic anemia and plastic anemia), degenerative diseases of the musculoskeletal system (including but not limited to osteoporosis and arthritis) aspirin-sensitive rhinosinusitis, cystic fibrosis, multiple sclerosis, kidney diseases and cancer pain.

Compounds of Formula III, as inhibitors of the CDKs, can modulate the level of cellular RNA and DNA synthesis. These agents would therefore be useful in the treatment of viral infections (including but not limited to HIV, human papilloma virus, herpesvirus, poxvirus, Epstein-Barr virus, Sindbis virus and adenovirus).

Compounds of Formula III may also be useful in the chemoprevention of cancer. Chemoprevention is defined as inhibiting the development of invasive cancer by either blocking the initiating mutagenic event or by blocking the progression of pre-malignant cells that have already suffered an insult or inhibiting tumor relapse.

Compounds of Formula III may also be useful in inhibiting tumor angiogenesis and metastasis.

Compounds of Formula III may also act as inhibitors of other protein kinases, e. g. , protein kinase C, her2, raf 1, MEK1, MAP kinase, EGF receptor, PDGF receptor, IGF receptor, P13 kinase, wee1 kinase ; Src, Abl and thus be effective in the treatment of diseases associated with other protein kinases.

Another aspect of this invention is a method of treating a mammal (e. g., human) having a disease or condition associated with the CDKs by administering a therapeutically effective amount of at least one compound of Formula it, or a pharmaceutically acceptable salt or solvate of said compound to the mammal.

A preferred dosage is about 0.001 to 500 mg/kg of body weight/day of the

compound of Formula 111. An especially preferred dosage is about 0.01 to 25 mg/kg of body weight/day of a compound of Formula i ! i, or a pharmaceutical acceptable salt or solvate of said compound.

The compounds of this invention may also be useful in combination (administered together or sequentially) with one or more of anti-cancer treatments such as radiation therapy, and/or one or more anti-cancer agents selected from the group consisting of cytostatic agents, cytotoxic agents (such as for example, but not limited to, DNA interactive agents (such as cisplatin or doxorubicin) ); taxanes (e. g. taxotere, taxol) ; topoisomerase 11 inhibitors (such as etoposide); topoisomerase I inhibitors (such as irinotecan (or CPT-11), camptostar, or topotecan); tubulin interacting agents (such as paclitaxel, docetaxel or the epothilones) ; hormonal agents (such as tamoxifen); thymidilate synthase inhibitors (such as 5-fluorouracil) ; anti-metabolites (such as methoxtrexate) ; alkylating agents (such as temozolomide (TEMODAR from Schering-Plough Corporation, Kenilworth, New Jersey), cyclophosphamide) ; Farnesyl protein transferase inhibitors (such as, SARASAR TM (4- [2- [4- [ (l 1 R)- 3, 10-dibromo-8-chloro-6, 11-dihydro-5H-benzo [5,6] cyclohepta [1,2-b] pyridin-11-yl- ]-1-piperidinyl]-2-oxoehtyl]-1-piperidinecarboxamide, or SCH 66336 from Schering-Plough Corporation, Kenilworth, New Jersey), tipifarnib (Zarnestrae or R115777 from Janssen Pharmaceuticals), L778, 123 (a farnesyl protein transferase inhibitor from Merck & Company, Whitehouse Station, New Jersey), BMS 214662 (a farnesyl protein transferase inhibitor from Bristol-Myers Squibb Pharmaceuticals, Princeton, New Jersey); signal transduction inhibitors (such as, Iressa (from Astra Zeneca Pharmaceuticals, England), Tarceva (EGFR kinase inhibitors), antibodies to EGFR (e. g. , C225), GLEEVEC (C-abl kinase inhibitor from Novartis Pharmaceuticals, East Hanover, New Jersey); interferons such as, for example, intron (from Schering-Plough Corporation), Peg-Intron (from Schering-Plough Corporation); hormonal therapy combinations; aromatase combinations; ara-C, adriamycin, cytoxan, and gemcitabine.

Other anti-cancer (also known as anti-neoplastic) agents include but are not limited to Uracil mustard, Chlormethine, Ifosfamide, Melphalan, Chlorambucil, Pipobroman, Triethylenemelamine,

Triethylenethiophosphoramine, Busulfan, Carmustine, Lomustine, Streptozocin, Dacarbazine, Floxuridine, Cytarabine, 6-Mercaptopurine, 6-Thioguanine, Fludarabine phosphate, oxaliplatin, leucovirin, oxaliplatin (ELOXATIN TM from Sanofi-Synthelabo Pharmaeuticals, France), Pentostatine, Vinblastine, Vincristine, Vindesine, Bleomycin, Dactinomycin, Daunorubicin, Doxorubicin, Epirubicin, Idarubicin, Mithramycin, Deoxycoformycin, Mitomycin-C, L-Asparaginase, Teniposide 17a-Ethinylestradiol, Diethylstilbestrol, Testosterone, Prednisone, Fluoxymesterone, Dromostanolone propionate, Testolactone, Megestrolacetate, Methylprednisolone, Methyltestosterone, Prednisolone, Triamcinolone, Chlorotrianisene, Hydroxyprogesterone, Aminoglutethimide, Estramustine, Medroxyprogesteroneacetate, Leuprolide, Flutamide, Toremifene, goserelin, Cisplatin, Carboplatin, Hydroxyurea, Amsacrine, Procarbazine, Mitotane, Mitoxantrone, Levamisole, Navelbene, Anastrazole, Letrazole, Capecitabine, Reloxafine, Droloxafine, or Hexamethylmelamine.

If formulated as a fixed dose, such combination products employ the compounds of this invention within the dosage range described herein and the other pharmaceutically active agent or treatment within its dosage range. For example, the CDC2 inhibitor olomucine has been found to act synergistically with known cytotoxic agents in inducing apoptosis (J. Cell Sci., (1995) 108, 2897.

Compounds of Formula III may also be administered sequentially with known anticancer or cytotoxic agents when a combination formulation is inappropriate.

The invention is not limited in the sequence of administration; compounds of Formula III may be administered either prior to or after administration of the known anticancer or cytotoxic agent. For example, the cytotoxic activity of the cyclin-dependent kinase inhibitor flavopiridol is affected by the sequence of administration with anticancer agents. Cancer Research, (1997) 57,3375. Such techniques are within the skills of persons skilled in the art as well as attending physicians.

Accordingly, in an aspect, this invention includes combinations comprising an amount of at least one compound of Formula i) t, or a pharmaceutically acceptable salt or solvate thereof, and an amount of one or more anti-cancer

treatments and anti-cancer agents listed above wherein the amounts of the compounds/treatments result in desired therapeutic effect.

The pharmacological properties of the compounds of this invention may be confirmed by a number of pharmacological assays. The exemplified pharmacological assays which are described later have been carried out with the compounds according to the invention and their salts.

This invention is also directed to pharmaceutical compositions which comprise at least one compound of Formula III, or a pharmaceutically acceptable salt or solvate of said compound and at least one pharmaceutical acceptable carrier.

For preparing pharmaceutical compositions from the compounds described by this invention, inert, pharmaceutical acceptable carriers can be either solid or liquid. Solid form preparations include powders, tablets, dispersible granules, capsules, cachets and suppositories. The powders and tablets may be comprised of from about 5 to about 95 percent active ingredient.

Suitable solid carriers are known in the art, e. g. , magnesium carbonate, magnesium stearate, talc, sugar or lactose. Tablets, powders, cachets and capsules can be used as solid dosage forms suitable for oral administration.

Examples of pharmaceutical acceptable carriers and methods of manufacture for various compositions may be found in A. Gennaro (ed.), Remington's Pharmaceutical Sciences, 18th Edition, (1990), Mack Publishing Co. , Easton, Pennsylvania.

Liquid form preparations include solutions, suspensions and emulsions.

As an example may be mentioned water or water-propylene glycol solutions for parenteral injection or addition of sweeteners and opacifiers for oral solutions, suspensions and emulsions. Liquid form preparations may also include solutions for intranasal administration.

Aerosol preparations suitable for inhalation may include solutions and solids in powder form, which may be in combination with a pharmaceutical acceptable carrier, such as an inert compressed gas, e. g. nitrogen.

Also included are solid form preparations that are intended to be converted, shortly before use, to liquid form preparations for either oral or

parenteral administration. Such liquid forms include solutions, suspensions and emulsions.

The compounds of the invention may also be deliverable transdermally.

The transdermal compositions can take the form of creams, lotions, aerosols and/or emulsions and can be included in a transdermal patch of the matrix or reservoir type as are conventional in the art for this purpose.

The compounds of this invention may also be delivered subcutaneously.

Preferably the compound is administered orally or intravenously.

Preferably, the pharmaceutical preparation is in a unit dosage form. In such form, the preparation is subdivided into suitably sized unit doses containing appropriate quantities of the active component, e. g. , an effective amount to achieve the desired purpose.

The quantity of active compound in a unit dose of preparation may be varied or adjusted from about 1 mg to about 100 mg, preferably from about 1 mg to about 50 mg, more preferably from about 1 mg to about 25 mg, according to the particular application.

The actual dosage employed may be varied depending upon the requirements of the patient and the severity of the condition being treated.

Determination of the proper dosage regimen for a particular situation is within the skill of the art. For convenience, the total daily dosage may be divided and administered in portions during the day as required.

The amount and frequency of administration of the compounds of the invention and/or the pharmaceutically acceptable salts thereof will be regulated according to the judgment of the attending clinician considering such factors as age, condition and size of the patient as well as severity of the symptoms being treated. A typical recommended daily dosage regimen for oral administration can range from about 1 mg/day to about 500 mg/day, preferably 1 mg/day to 200 mg/day, in two to four divided doses.

Another aspect of this invention is a kit comprising a therapeutically effective amount of at least one compound of Formula lil, or a pharmaceutical acceptable salt or solvate of said compound and a pharmaceutically acceptable carrier, vehicle or diluent.

Yet another aspect of this invention is a kit comprising an amount of at least one compound of Formula lil, or a pharmaceutically acceptable salt or solvate of said compound and an amount of at least one anticancer therapy and/or anti-cancer agent listed above, wherein the amounts of the two or more ingredients result in desired therapeutic effect.

The invention disclosed herein is exemplified by the following preparations and examples which should not be construed to limit the scope of the disclosure.

Alternative mechanistic pathways and analogous structures will be apparent to those skilled in the art.

Where NMR data are presented, H spectra were obtained on either a Varian VXR-200 (200 MHz, 1 H), Varian Gemini-300 (300 MHz) or XL-400 (400 MHz) and are reported as ppm down field from Me4Si with number of protons, multiplicities, and coupling constants in Hertz indicated parenthetically. Where LC/MS data are presented, analyses was performed using an Applied Biosystems API-100 mass spectrometer and Shimadzu SCL-10A LC column: Altech platinum C18, 3 micron, 33mm x 7mm ID ; gradient flow: 0 min-10% CH3CN, 5 min-95% CH3CN, 7 min-95% CH3CN, 7.5 min-10% CH3CN, 9 min-stop. The retention time and observed parent ion are given.

The following solvents and reagents may be referred to by their abbreviations in parenthesis: Thin layer chromatography: TLC dichloromethane : CH2CI2 ethyl acetate: AcOEt or EtOAc methanol : MeOH trifluoroacetate : TFA triethylamine : Et3N or TEA butoxycarbonyl : n-Boc or Boc nuclear magnetic resonance spectroscopy: NMR liquid chromatography mass spectrometry: LCMS high resolution mass spectrometry: HRMS milliliters : mL millimoles : mmol

microliters : gui grams: g milligrams : mg room temperature or rt (ambient): about 25°C. dimethoxyethane: DME EXAMPLES In general, the compounds described in this invention can be prepared through the general routes described below in Scheme 1. Treatment of the Scheme 1

starting nitrile with potassium t-butoxide and ethyl formate gives rise to the intermediate enol 2 which upon treatment with hydrazine gives the desired substituted 3-aminopyrazole. Condensation of compounds of type 3 with the appropriately functionalized keto ester of type 5 gives rise to the pyridones 6 as shown in Scheme 3. The keto esters used in this general route are either commercially available or can be made as illustrated in Scheme 2.

Scheme 2

The chlorides of type 9 can be prepared by treatment of the pyridones 8 with POCI3. When R2 is equal to H, substitution in this position is possible on the compounds of type 9 by electrophilic halogenation, acylation, and various other electrophilic aromatic substitutions.

Introduction of the N7-amino functionality can be accomplished through displacement of the chloride of compounds of type 9 by reaction with the appropriate amine as shown in Scheme 3.

Scheme 3 p2 O O H2N R2 H + Irl \ R'POC13 R3'A-T"0 N-N pyr. reflux N-N R4 PYr. N, N/ R O CRI 6 7 ci 8 9 R2 R NH2 R' N R K2C03 ; CH3CN HN, R R 10

Condensation of compounds of type 7 with the appropriately functionalized malonate ester of type 11 gives rise to the pyridones 13 as shown in Scheme 4.

The chlorides of type 14 can be prepared by treatment of the pyridones 13 with POC13. When R2 is H, substitution in this position is possible on compounds of type 9 by electrophilic halogenation, acylation, and various other electrophilic aromatic substitutions.

Incorporation of the N7-amino functionality can be accomplished through regioselective displacement of the chloride of compounds of type 14.

Incorporation of the N5-amino functionality by addition of an appropriate amine at higher temperature.

Scheme 4

R2 O O H2N R2 H R2 AcOH N POCI3 \ N CI R I reflux Cl 11 g 14 R2 R5. R6 R2 R5 R. NH2 RN\ y H \ _N\ N. Rs iPr2NEt ; dioxane R O Cl 11 7 13 14 R >2 R5> R6 R2 IR5 Pr2NEt ; dioxane N R4 RT HN. 75 °C HNsR R 15 16 Alternatively, condensations of the aminopyrazoles of type 7 with an appropriately functionalize keto ester as prepared in Scheme 5, leads to compounds of type 13 as shown in Scheme 4.

Scheme 5

The chlorides of type 14 can be prepared by treatment of the pyridones 13 with POCI3. When R2 is equal to H, substitution in this position is possible on compounds of type 14 by electrophilic halogenation, acylation, and various other electrophilic aromatic substitutions.

Incorporation of the N7-amino functionality can be accomplished through displacement of the chloride of compounds of type 15.

Preparative Examples : PREPARATIVE EXAMPLE 1:

Step A:

A procedure in German patent DE 19834047 A1, p 19 was followed. To a solution of KOtBu (6.17 g, 0.055 mol) in anhydrous THF (40 mL) was added, dropwise, a solution of cyclopropylacetonitrile (2.0 g, 0.025 mol) and ethyl formate (4.07 g, 0.055 mol) in anhydrous THF (4 mL). A precipitate formed immediately. This mixture was stirred for 12 hr. It was concentrated under vacuum and the residue stirred with Et20 (50 mL). The resulting residue was decanted and washed with Et20 (2 x 50 mL) and Et20 removed from the residue under vacuum. The residue was dissolved in cold H20 (20 mL) and pH adjusted to 4-5 with 12 N HCI. The mixture was extracted with CH2CI2 (2 x 50 mL). The organic layers were combined, dried over MgS04 and concentrated under vacuum to give the aldehyde as a tan liquid.

Step B :

The product from Preparative Example 1, Step A (2.12 g, 0.0195 mol), NH2NH2 H2O (1.95 g, 0.039 mol) and 1.8 g (0.029 mole) of glacial CH3CO2H (1.8 g, 0.029 mol) were dissolved in EtOH (10 mL). It was refluxed for 6 hr and concentrated under vacuum. The residue was slurried in CH2CI2 (150 mL) and the pH adjusted to 9 with 1 N NaOH. The organic layer was washed with brine, dried over MgS04 and concentrated under vacuum to give the product as a waxy orange solid.

PREPARATIVE EXAMPLES 2-4: By essentially the same procedure set forth in Preparative Example 1, only substituting the nitrile shown in Column 2 of Table 2, the compounds in Column 3 of Table 2 were prepared: TABLE 2 Prep. Column 2 Column 3 Ex. 2 con NH2 N'N N N H 3 H3CCN N 3 zu H H 3. 10 F3CC F3C NH2 '/ruz ZU H PREPARATIVE EXAMPLE 4

2-Carbomethoxycyclopentanone (6.6 ml, 0.05 mol) in THF (15 ml) was added dropwise to a vigorously stirred suspension of NaH (60% in mineral oil, 4 g, 0.1 mol) in THF (100 mi) at 0-10 °C. When bubbling ceased, the reaction mixture was treated at the same temperature with CICOOMe (7.8 ml, 0.1 mol) in THF (15 ml). The resulted off-white suspension was stirred for 30 minutes at room temperature and 30 minutes under reflux. The reaction was monitored by TLC for disappearance of starting material. The reaction mixture was quenched with water carefully and partitioned between ethyl acetate and saturated solution of ammonium chloride in a funnel. Shaken and separated, the organic layer was washed with brine and dried over anhydrous sodium sulfate. Solvents were removed, and the residue was purified by flash chromatography, eluted with 5% and then 10% ethyl acetate in hexane. 9.4 g colorless oil was obtained with 94% yield.'H NMR (CDCI3) 8 3.90 (s, 3H), 3.73 (s, 3H), 2.65 (m, 4H), 1.98 (m, 2H).

PREPARATIVE EXAMPLE 5 To lithium diisopropylamide solution in THF (2.0 N, 0.04 mol) at-65 °C, was added dropwise 2, 2-dicarbomethoxycyclopentanone (4 g, 0.02 mol) in THF (60 ml). The resulted reaction mixture was stirred at the same temperature before adding methyl chloroformate (1.54 ml, 0.02 mol). Reaction mixture stirred for an hour and poured into saturated ammonium chloride solution with some ice. This solution was extracted three times with ether, and the combined ethearal layers were dried over sodium sulfate. Solvents were removed in vacuo, and the residue was purified by flash chromatography, eluted with 30% increased to 50% ethyl acetate in hexane. 2.3 g yellowish oil was obtained with 58% yield. 1H NMR (CDCI3) â 3.77 (s, 6H), 3.32 (t, 1H), 3.60-3. 10 (m, 4H).

PREPARATIVE EXAMPLE 6:

The reactions were done as outlined in (K. O. Olsen, J. Org. Chem., (1987) 52,4531-4536). Thus, to a stirred solution of lithium diisopropylamide in THF at-65 to-70 C was added freshly distilled ethyl acetate, dropwise. The resulting solution was stirred for 30 min and the acid chloride was added as a solution in THF. The reaction mixture was stirred at-65 to-70° C for 30 min and then terminated by the addition of 1 N HCI solution. The resulting two- phased mixture was allowed to warm to ambient temperature. The resulting mixture was diluted with EtOAc (100 mL) the organic layer was collected. The aqueous layer was extracted with EtOAc (100 mL). The organic layers were combined, washed with brine, dried (Na2SO4), and concentrated in vacuo to give the crude 8-keto esters, which were used in the subsequent condensations.

PREPARATIVE EXAMPLES 7-19: By essentially the same procedure set forth in Preparative Example 6 only substituting the acid chlorides shown in Column 2 of Table 3, the ?-keto esters shown in Column 3 of Table 3 were prepared: TABLE 3 Prep. Column 2 Column 3 DATA Ex. 7 O O O LCMS : MH+ = 223 CI I v OEt 1 OEt 8 0 O O LCMS : Mu =253 1 ci OEt MeO MeO OMe OMe 9000LCMS : MH = 261 ci OEt HCI Cl 10 0 O p MH+ = 199 /-a (Y-OE. 12 0 0 0 OEt _ , <Y-c ! rrroEt 13 (3 (5C'LCMS : ci OEt MH+ = 271 Br Br 14 O 0 0 Yield = quant Mu+ =249 ci out 15 0 0 0 Yield = quant MH =237 'OEt \-o \-o O O O O Yield = quant MH+ = 262 OEt ci CI CI CI 17 Yield 48 N\ C I N\ MH+ = 195 poet 1 con "N"N 18 0 O O Yield = 99 MH+ =199 ci OEt Yield=77% Oz O Ow O O 1H NMR (CDCI3) ô 7. 42 (t, AJk {OEt 1 H), 6. 68 (d, 2H), 4. 29 (q, vOz WOz 2H), 3. 97 (d, 2H), 3. 95 (s, 3H), 1. 38 (t, 3H).

PREPARATIVE EXAMPLE 20 : To a solution of the acid in THF was added Et3N, followed by isobutyl chloroformate at-20 to-30°C. After the mixture was stirred for 30 min at-20 to -30°C, triethylamine hydrochloride was filtered off under argon, and the filtrate was added to the LDA-EtOAc reaction mixture (prepared as outlined in Method A) at-65 to-70°C. After addition of 1 N HCI, followed by routine workup of the reaction mixture and evaporation of the solvents, the crude p-keto esters were isolated. The crude material was used in the subsequent condensations.

PREPARATIVE EXAMPLES 21-28: By essentially the same conditions set forth in Preparative Example 20 only substituting the carboxylic acid shown in Column 2 of Table 4, the compounds shown in Column 3 of Table 4 were prepared: TABLE 4 Prep. Ex. Column 2 Column 3 CMPD 21 OH OEt Yield = 99% f T"F T n T MH-913 O O MH+=213 22 ci CI Yield = 70% OH OEt MH+ = 275 . i 23 C02H O O Yield = quant MH+ =213 "OEt 24 Yield ant MH+ =211 0 C02H 0 OEt O OEt 25 C02H O O Yield = 99 MH+ = 334 OUT CbZ J Cbz'N 26 0 0 Yield = 99 CbzN OEt MH+-334 Cbz'N C02H 27 C02H 0 0 Yield = 99 M H+ = 334 Omet Cbz I N'Cbz 28 Yield=77% 'H NMR (CDCI3) 8 O O O 4. 21 (q, 2H), 3. 95 (d, OH OEt 2H), 3. 93-3. 79 (m, 4H), 3. 52 (s, 2H), 2. 65 (m, 1 H), 1. 25 (t, 3H), 1. 23- 1. 2 (m, 2H).

PREPARATIVE EXAMPLE 29:

A solution of 3-aminopyrazole (2. 0g, 24.07 mmol) and ethyl benzoylacetate (4.58 mL, 1.1 eq. ) in AcOH (15 mL) was heated at reflux for 3 hours. The reaction mixture was cooled to room temperature and concentrated in vacuo. The resulting solid was diluted with EtOAc and filtered to give a white solid (2.04 g, 40% yield).

PREPARATIVE EXAMPLES 30-73: By essentially the same procedure set forth in Preparative Example 29 only substituting the aminopyrazole shown in Column 2 of Table 5 and the ester shown in Column 3 of Table 5, the compounds shown in Column 4 of Table 5 were prepared: TABLE 5 Prep. Column 2 Column 3 Column 4 Column 5 Ex. 30 nu2 0 0 O^CH3 N I H/F F I N, N F N-N u 31 Ni2 0 0 H 0 N .. 'r " Cl Nn N Cl ci N-N y-N 0 32 NH2 0 0 CF3 OCH zon CF3 % N-N 0 O 34NHsC) (5") H 33 NH2 00 O H I N'N O non 34 NH2 00 H N W N 3 -- I N OCH3 NON H H N 35 N 0 0 O^CH3 N N N 36 NH o o-_ nu2 H O^CH3 I N O'CH, N a ZON NIN N-N nu2 nu , N/ N'N 0 37. 10 F3 0 0 CF3 H O^CH3 N "s H I H 38 NH2 0 0 ci 37. 1 0 WIH2 O 38 N OCH3 N M c. f T 'N H 39 NH2 0 0 N OEt N .. _.. 0 non OYE-N 40 NH2 O O Me0 f r N X t ; MeO :-5] OEt Out N wu Met ORME OYE 0 C ! OEt CI Cl y cl O N OEt N S S I N N 42 NH2 O O k H ¢0N C kOEt S4X ? 0 N 43 NH2 OEt H N O O I NN I N N H I Non 44 NH2 ci CI out OEt N N I CI I I N, NI H 0 45 NH2 O O H N OEt 0 45. NHs00H H N 46 Et02C N / N/C02Et OEt N n" Nez H 47 Nu2 0 0 N OEt N I N- Nn 0 H N 48 NH2 o o NCg out in I, N I I N H NC r, N O 49 NH2 0 0 H OEt N OEt N 50 NH2 O O I N Non , I N'N H 51 NH2 0 0 F3C H F) A N N'N H0 52 NH2 H3C N Hs"OEt N'N H O 53 A H2 o out Non H O 54 NH2 O O OEt H O 55 NH2 O O N OEt 55 NH2 I N N H I Non N N-N 56 NH2 Et02C-C02Et Et02C N v ho H O 57 NH2 0 0 I N I H Br y N-N 0 0 O 58 NH2 O O HO N Yield = in il EtOOEt NN N H OH 152 59 NH2 0 o Yield = N OEt 46+ N mi 268 N-N OH 60 NH2 0 O rO Yield = N out N MH+ H 255 W N, N OH 61 NH2 o o _ _ Yield = OEt OEt N 80 + OH 62 MHz cl cl N-N 280 OH 62 NH2 N\ o o N I MH*-_ 72 OEt C N I, N H N-N OH 63 NHa o p oh OEt S OH \ N, y 218 Oh 64 NHz o o Yield = OEt H N =218 OH 65 NH2 o OH Yield Omet H N =232 OH 66 NH2 N Yield = 30 \ N, N MH+ 0 OEt OH =230 0 67 NH2 o 0 1 Cbz'N Yield N OEt N 80 N'N =353 OH 68 NH2 0 0 Cbz Yield= I I Yield Mu N N H =353 N, N OH Yield I OEt OEt'N 42 N H'Cbz Cbz N-N =353 OH 70 NH2 H 0 0 0 N N OEt "0 O 71 NH2 0 0 H OEt ob N N 0 N- H 0 72 I Br NH2 O O N OEt N H N-N O', N N K 0-Ny 0 Q 73 NH2 0 0 0 u [1N'N OEt NI H N-N P-" 0 PREPARATIVE EXAMPLE 74:

Ethyl benzoylacetate (1.76 mL, 1.1 eq. ) and 3-amino-4-cyanopyrazole (1.0 g, 9.25 mmol) in AcOH (5.0 mL) and H20 (10 mL) was heated at reflux 72 hours. The resulting solution was cooled to room temperature, concentrated in vacuo, and diluted with EtOAc. The resulting precipitate was filtered, washed with EtOAc, and dried in vacuo (0.47 g, 21 % yield).

PREPARATIVE EXAMPLE 75 A procedure in US patent 3,907, 799 was followed. Sodium (2.3 g, 2 eq.) was added to EtOH (150 mL) portionwise. When the sodium was completely

dissolved, 3-aminopyrazole (4.2 g, 0.05 mol) and diethyl malonate (8.7 g, 1.1 eq. ) were added and the resulting solution heated to reflux for 3 hours. The resulting suspension was cooled to room temperature and filtered. The filter cake was washed with EtOH (100 mL) and dissolved in water (250 mL). The resulting solution was cooled in an ice bath and the pH adjusted to 1-2 with concentrated HCI. The resulting suspension was filtered, washed with water (100 mL) and dried under vacuum to give a white solid (4.75 g, 63% yield).

PREPARATIVE EXAMPLES 76-78: By essentially the same procedure set forth in Preparative Example 75 only substituting the compound shown in Column 2 of Table 6, the compounds shown in Column 3 of Table 6 are prepared: TABLE 6 Prep. Column 2 Column 3 Ex. 76 H2N H . N N, H N, N ? vu 0 77 \ \, / N'N H I H2N H N O N N, nu 0 -N PREPARATIVE EXAMPLE 79:

A solution of the compound prepared in Preparative Example 29 (1.0 g, 4.73 mmol) in POCI3 (5 mL) and pyridine (0.25 mL) was stirred at room

temperature 3 days. The resulting slurry was diluted with Et2O, filtered, and the solid residue washed with Et20. The combined Et20 washings were cooled to 0°C and treated with ice. When the vigorous reaction ceased, the resulting mixture was diluted with H20, separated, and the aqueous layer extracted with Et20. The combined organics were washed with H20 and saturated NaCI, dried over Na2SO4, filtered, and concentrated to give a pale yellow solid (0. 86 g, 79% yield). LCMS: MH+=230.

PREPARATIVE EXAMPLE 80-122 : By essentially the same procedure set forth in Preparative Example 79, only substituting the compound shown in Column 2 of Table 7, the compounds shown in Column 3 of Table 7 were prepared: TABLE 7 Prep. Column 2 Column 3 CMPD Ex. 80 MS : MH =248 N I/N N F N-N F \ non O Cl 81 Cl Cl 9f N +, N ci N-N ci N-N + O ci 82 CF3 CF3 MS : MH =298 H N-N N-N I mu cul 83 H MS : MH+=196 N N'N N'N 0 CI 84 H MS : MH+=210 WN_N Cl 0 Ci O ci 85 0 ci N ion i, >, y N'N N'N O CRI ci 86 MS : MH+=272 H /N I/N i N-N N-N O ci 0 cri H I/N, I/N, W NON O CRI 87. 10 H CF3 CF3 /NON N N Nu O CI 0 CN I CN MS : MH =255 H H CN CN N N N N -ton 0 ci 89 ci ci I/N, I/N, o cri 90 I. H _. I \ Yield = 65% N MS : MH+ 260 OMe N-N OMe N-N cri 91 MeO meo Yield = 35% J MS : MH+ = 290 MeO N MeO N- i N-N CI 0 ci 92 H Yield = 32% ci N ci N MS : MH+ = 298 CI NN C) W N Cl Cl 93 H Yield = 45% S ; ? S44 MS : MH+ = 236 N N N N Non 94 H N Yield = 100% N N N-N-N LCMS : MH+ Non -N N ci 250 95 ci H ci Yield = 88% ci MS : MH+=314 CI N, N/CI W N N c lu 96 H Yield=43% MS : MH+=223 N ci 0 0 97 H C02Et--C02Et Yieid=30% I N N MS : MH+=295 II N\N NN O CL 98 H Yield=98% N MS : MH+=244 y N-N- N N 99 N NC I/N, I/N, N 00 Non Fizz N'N N'N 0Ci 10N O N'/ NON N N 3 i l, Non ! ! A CI 103 H C N HsC N H3C Nn non-N N'N ci 104 N-N\ ^ 104 H 105 \N 1 N -N ce 105 N. N\ ^ -N cri cri 106 H N-N N-N C) cl EtO2C 45% yield ; MS : w N N M H+=226 Non-N -N ci 108 i H MS : 108 MS : H Br N, N Br W N, N O ci (3Cj 109 Yield quant MH+ = 286 N N W N OH ci 110 FO ZO Y ; eld = 50 0 0 MH+ 272 N N kN N OH XI 111 ci Yield 85 MH+ = 299 I ion ci N-N ci N-N OH Cl OH Ct 112 (N N Yield 97 MH+ = 231 N N N N C ' i'l N rN'l OH OH CI 113 OH ci Yield 45 N N MH+ 236 % oN-N 4C1 N-N OH 114 Yield quant. MH+ =236 NEZ OH0 W NON OH 115 Yield = 57 L. JL. N L J N MH'=250 MH+ =250 NEZ H N N, N OH y 116 N N Yield = 89 b7 MH+ =248 W NON OH) 117 CbzN CbzN Yield = 96 MH+ =371 W N, l y OH0 OH CI 118 Cbz Cbz Yield = 99 N N MH+ =371 N N N N OU 119 Yield = 50 Mu+ =371 'N'N Cbz N-N Cbz N-N OH CI 120 H 0 Yield=57% LCMS : MH+=224 N cl 121 H OEt OEt Yield=34% N LCMS : MH+=226 N, N/ Cl 122 O,. Yield=100% Ot N+ ! 1H NMR (CDCI3) 0 /0 8 8. 53 (d, 1 H), CI/7. 66 (t, 1 H), N-N O 7. 51 (s, 1 H), 7. 45 (d, 1 H), 6. 84 (d, 2H).

PREPARATIVE EXAMPLE 123

POCI3 (62 mL) was cooled to 5 °C under nitrogen and dimethylaniline (11.4 g, 2.8 eq. ) and the compound prepared in Preparative Example 75 (4. 75 g,

0.032 mol). The reaction mixture was warmed to 60 °C and stirred overnight.

The reaction mixture was cooled to 30 °C and the POC13 was distilled off under reduced pressure. The residue was dissolved in CH2C12 (300 mL) and poured onto ice. After stirring 15 minutes, the pH of the mixture was adjusted to 7-8 with solid NaHC03. The layers were separated and the organic layer was washed with H20 (3 x 200 mL), dried over MgS04, filtered, and concentrated. The crude product was purified by flash chromatography using a 50: 50 CH2CI2 : hexanes solution as eluent to elute the dimethyl aniline. The eluent was then changed to 75: 25 CH2CI2 : hexanes to elute the desired product (4.58 g, 77% yield). MS: MH+=188.

PREPARATIVE EXAMPLES 124-126 By essentially the same procedure set forth in Preparative Example 123 only substituting the compound in Column 2 of Table 8, the compounds shown in Column 3 of Table 8 are prepared: TABLE 8 Prep. Column 2 Column 3 Ex. 124 H N Cl N N'N N'N O CL 125 0 ci O N CI N N'N N'N Sr ci N N 0C) 126 H CH3 CH3 N Cl N N'N N'N 0 CI 0Cj PREPARATIVE EXAMPLE 127:

A solution of the compound prepared in Preparative Example 79 (0.10 g, 0.435 mmol) in CH3CN (3 mL) was treated with NBS (0.085 g, 1.1 eq. ). The reaction mixture was stirred at room temperature 1 hour and concentrated under reduced pressure. The crude product was purified by flash chromatography using a 20% EtOAc-in-hexanes solution as eluent (0.13 g, 100% yield).

LCMS: MH+=308.

PREPARATIVE EXAMPLES 128-164: By essentially the same procedure set forth in Preparative Example 127 only substituting the compounds shown in Column 2 of Table 9, the compounds shown in Column 3 of Table 9 were prepared: TABLE 9 Prep. Column 2 Column 3 CMPD Ex. 128 Br MS : MH+- Bu 326 F F Ct Ct CI CI 129 Br MS : MH+= Br N N 342 Cf NN CI \ NN CI CI C) Ci 130 CFs CF3 MS : MH = 376 Br N-N N-N Ci ci 131 Br MS : Ci Cl MH+=274 N y-N \ Nz ci cl 132 Br MS : N MH+=288 N N, /N'/ ci ci ci ci ber . bd cri C) Ct C CI 134 Br Yield = 75% N N MS : MH+= '/y Ta OMe YN-N OMe YN~N 338 Cl Cl 135 M0 Me0 Yield = 52% Br Me0 I N Me0 N MS : MH = Zon W Nz cl 136 s _ Yield = 87% Yjg, d = 87% cl. N ci N MS : MH+= Cl cul ci N-N cl N-N 376 ci 137 Br Yield = 100% S N g N MS : MH+ L. N kN 316 CI CI Cl Cl 13 N Br Yield = 92% N MS : MH 330 CI NN 330 ci 139 Ct C) Br Yietd=82% N N MS : MH+ Cl CI 3 5 Ci CRI 140 \ W Br Yield=88% 9Xf, N sn 9>"N XfA MS : MS : \ N''.' MH+=308 C ! cl Cl 141 W Br Yield=100% MU : N-N N-N MH+=322 Ci CI 142 CI N Br M 6 l Cl 1 Cl + 1 42 Cl, N < MH =266 CI N _N ci N-N CI ci 143 NC c I Br >N-N YN_N \ N N N N- N N N\ N 0 non 145/ N/ Br N \ IV NJ N % N 146 F3 N Br F C-TF3 Cl YNoN Nz cri CI 147 H3C N Br \ N H3C N ' l N-N ci N Ci 0 T 1 w !, W BER N 0 149 Cl Cl non -N ci N-N cri 150 ber N-N N-N cl 0Qj 151 i, Br LCMS : , N , N MH+= 386 Br N-N Br \/N, N CI CI 152 Yield = quant Br mu+ 364 N \ N, /\ N sl CJ ! ci cl 153 r-O/-0 Yield = quant O/MH+ = 353 Br \ N N-N N-N ci cri CI CI 154 ci ci Yield 95 Br MH+ = 378 TrY TY N CjC) 155 N N Yield = 77 MH+ = 311 N-N N-N ci ci CI CI 156 Yield =quant. Br MH+ =314 Cl Cl i ! CjC !) CI CI 1 57 _ _ Yield = 99 N N MH* =328 gon CDC N, N N, N ce 158 N Br Yield = 98 X MH+ =326 N, N HCI CL 159 Cbz. N Cbz, N Yield = 99 +, N <, N4 MH =449 Br MH*-449 N-N N-N CjCj CI CI 160 Cbz Cbz Yield = 95 N N MH+ =449 Br N N, l N'/l NN CjCj 161 Yield = 72 N N MH+ =449 Nz Cbz N-N Cbz N-N Y X Cl Cl 162 r° Br rO Yield=98% N N LCMS : N N f N N d MH+=302 Cl Cl 163 OEt Br OEt Yield=95% N 0 N LCMS : N-N N-N MH+=305 Cl Cl 164 1-10 Br Yield=50% /'H NMR (CDC3) 8 I N-N/O w 8. 36 (s, 1 H), 7. 72 d 1 H CI NN ), 7. 20 (s, 1 H), Ci 6. 82 (d, 1 H), 3. 99 (s, 3H), 3. 90 (s, 3H) ; PREPARATIVE EXAMPLE 165:

A solution of the compound prepared in Preparative Example 80 (0.3 g, 1.2 mmol) in CH3CN (15 mL) was treated with NCS (0.18 g, 1.1 eq. ) and the resulting solution heated to reflux 4 hours. Additional NCS (0.032 g, 0.2 eq. ) added and the resulting solution was stirred at reflux overnight. The reaction mixture was cooled to room temperature, concentrated in vacuo and the residue purified by flash chromatography using a 20% EtOAc in hexanes solution as eluent (0.28 g, 83% yield). LCMS: MH+= 282.

PREPARATIVE EXAMPLE 166-167: By essentially the same procedure set forth in Preparative Example 165 only substituting the compound shown in Column 2 of Table 10, the compound shown in Column 3 of Table 10 was prepared: TABLE 10 Prep. Ex. Column 2 Column 3 CMPD 166 ci Yield = 82% - N Non w non o 167 CI N CI ci = 286 N/ ci N ci 0

PREPARATIVE EXAMPLE 167.10 : By essentially the same procedure set forth in Preparative Example 165 only substituting N-iodosuccinimide, the above compound was prepared.

PREPARATIVE EXAMPLE 168:

To a solution of the compound from Preparative Example 79 (1.0 g, 4.35 mmol) in DMF (6 mL) was added POCI3 (1.24 mL, 3.05 eq. ) and the resulting mixture was stirred at room temperature overnight. The reaction mixture was cooled to 0°C and the excess POCI3 was quenched by the addition of ice. The resulting solution was neutralized with 1 N NaOH, diluted with H20, and extracted with CH2CI2. The combined organics were dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by flash chromatography using a 5% MeOH in CH2CI2 solution as eluent (0.95 g, 85% yield) : LCMS: MH+=258.

PREPARATIVE EXAMPLE 169: By essentially the same procedure set forth in Preparative Example 168 only substituting the compound prepared in Preparative Example 80, the above compound was prepared (0.45 g, 40% yield).

PREPARATIVE EXAMPLE 170: To a solution of the product of Preparative Example 169 (0.25 g, 0.97 mmol) in THF was added NaBH4 (0.041 g, 1.1 eq. ) and the resulting solution was stirred at room temperature overnight. The reaction mixture was quenched by the addition of H20 and extracted with CH2CI2. The combined organics were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by flash chromatography using a 60: 40 hexanes: EtOAc mix as eluent (0.17 g, 69% yield). MS: MH+=260.

PREPARATIVE EXAMPLE 171:

A solution of the compound prepared in Preparative Example 170 (0.12 g, 0.462 mmol), dimethyl sulfate (0.088 mL, 2.0 eq), 50% NaOH (0.26 mL) and catalytic Bu4NBr in CH2CI2 (4 mL) was stirred at room temperature overnight.

The reaction mixture was diluted with H20 and extracted with CH2CI2. The combined organics were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by flash chromatography using a 30% EtOAc-in-hexanes solution as eluent (0.062 g, 48% yield).

PREPARATIVE EXAMPLE 172 To a solution of PPhs (4.07 g, 4.0 eq. ) and CBr4 (2.57 g, 2.0 eq. ) in CH2CI2 (75 mL) at 0 °C was added the compound prepared in Preparative Example 168 (1.0 g, 3.88 mmol). The resulting solution was stirred at 0 °C for 1 hour and concentrated under reduced pressure. The residue was purified by flash chromatography using a 20% EtOAc in hexanes solution as eluent (1.07 g, 67% yield).

PREPARATIVE EXAMPLE 173: By essentially the same procedure set forth in Preparative Example 172 only substituting the compound prepared in Preparative Example 169 the above compound was prepared (0. 5 g, 70% yield).

PREPARATIVE EXAMPLE 174:

The compound prepared in Preparative Example 127 (3.08 g, 10.0 mmol), 2.0 M NH3 in 2-propanol (50 mL, 100.0 mmol), and 37 % aqueous NH3 (10.0 mL) were stirred in a closed pressure vessel at 50°C for 1 day. The solvent was evaporated and the crude product was purified by flash chromatography using 3: 1 CH2CI2 : EtOAc as eluent. Pale yellow solid (2.30 g, 80%) was obtained.

LCMS : M+=289.

PREPARATIVE EXAMPLES 175-180: By essentially the same procedure set forth in Preparative Example 174 only substituting the compound shown in Column 2 of Table 11, the compounds shown in Column 3 of Table 11 were prepared.

TABLE 11 Prep. Column 2 Column 3 Ex. 1 75 < Br < Br Cl NH, N N N, N NN H2 cl nez Bu ber kN/N F N-N F N N NH2 177 Br Br N\ nez N-N N-N CI NH2 178 0 Br 0 Br N N N-N N-N CI NHs 1 9 i N-N N-N N, N W N-N 0 NH- 180 Br NN ONkN 03 Cl 03 N H2 /CI, NH2 PREPARATIVE EXAMPLE 181 :

The compound prepared in Preparative Example 80 (0.3 g, 1.2 mmol), K2CO3 (0. 33 g, 2 eq. ), and 4-aminomethylpyridine (0.13 mL, 1.1 eq. ) was heated to reflux overnight. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was diluted with H20 and extracted with CH2CI2. The combined organics were dried over Na2SO4, filtered and, concentrated. The crude product was purified by flash chromatography using a 5% (10% NH40H in MeOH) solution in CH2CI2 as eluent (0.051 g, 40% yield). LCMS: MH+=320.

PREPARATIVE EXAMPLE 182:

By essentially the same procedure set forth in Preparative Example 181 only substituting the compound described in Preparative Example 92, the above compound was prepared. LCMS: MH+=370.

PREPARATIVE EXAMPLE 183 : To a solution of the compound prepared in Preparative Example 123 (0.25 g, 1.3 mmol) in dioxane (5 mL) was added iPr2NEt (0.47 mL, 2.0 eq. ) and 3- aminomethylpyridine (0.15 ml, 1.1 eq. ). The resulting solution was stirred at room temperature 72 hours. The reaction mixture was diluted with H2O and extracted with EtOAc. The combined organics were washed with H20 and saturated NaCI, dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by flash chromatography using a 5% MeOH in CH2CI2 solution as eluent (0.29 g, 83% yield). MS: MH+=260.

PREPARATIVE EXAMPLES 184-187: By essentially the same procedure set forth in Preparative Example 183 only substituting the compound shown in Column 2 of Table 12, the compounds shown in Column 3 of Table 12 are prepared.

TABLE 12 Prep. Column 2 Column 3 Ex. 184 Br Br 4 Cl NS ; CI HAN N-N-N kan 184. 1 Br B CI N\ (CI N\ ( \ N N \ N N CI ClyN N N _-N ci HN 185 Et02C f Et02C N non ci HN C) HZ kan 1 6 Br Br N Br N Br \ NN N, N ci HN ICI ZON I N Br N Br Nz F N-N F N N Ci han ZON I I N 187. 1 1 1 N N N, N/ Ci HN ZON N 187. 11 l"N4, N4 N-N N-N I ho N /II N PREPARATIVE EXAMPLE 188 and PREPARATIVE EXAMPLE 189 :

To a solution of the compound prepared in Preparative Example 185 (1. 18 g, 3.98 mmol) in THF (35 mL) at-78 °C was added LAH (4.78 mL, 1M in Et20, 1.0 eq. ) dropwise. The reaction mixture was stirred at-78 °C for 3 hours at which time additional LAH (2.0 mL, 1 M in Et20, 0.42 eq. ) was added dropwise.

The reaction mixture was stirred an additional 1.25 hours and quenched by the addition of saturated Na2SO4 (8.5 mL). The reaction mixture was diluted with EtOAC (23 mL), H20 (2 mL), and CH30H (50 mL). The resulting slurry was filtered through a plug of Celite. The Celite was washed with CH30H and the filtrate dried with Na2SO4, filtered, and concentrated. The product was purified by flash chromatography using a CH2CI2 : CH30H (93: 7) solution as eluent to yield aldehyde as the first eluting product and alcohol as the second eluting product.

Preparative Example 188: (aldehyde) : 0.4 g, 39% yield. MS: MH+ = 254. Preparative Example 189: (alcohol) : 0.25 g, 24% yield. MS : MH+ = 256.

PREPARATIVE EXAMPLE 190:

To a solution of the compound prepared in Preparative Example 188 (0.075 g, 0.30 mmol) in THF (2.0 mL) at 0 °C was added CH3MgBr (0.3 mL, 3. 0M solution in Et20,3. 0 eq. ) dropwise. The resulting solution was stirred at 0 °C an additional 1.5 hours, warmed to room temperature, and stirred overnight.

Additional CH3MgBr (0.15 mL, 3. 0M in Et20, 1. eq. ) was added and the resulting solution stirred an additional 1.5 hours. The reaction mixture was cooled to 0 °C and quenched by the addition of saturated NH4CI. The resulting solution was diluted with CH2CI2 and H20 and extracted with CH2CI2. The combined organics were washed with saturated NaCI and dried over Na2SO4, filtered, and concentrated. The crude product was purified by flash chromatography using a CH2CI2 : CH30H (90: 10) solution as eluent (0.048 g, 60% yield). MS: MH+ = 270.

PREPARATIVE EXAMPLE 191: By essentially the same procedure set forth in Preparative Example 190 only substituting the compound prepared in Preparative Example 185 and using excess MeMgBr (5 eq. ), the above compound was prepared.

PREPARATIVE EXAMPLE 192:

The compound prepared in Preparative Example 181 (0.29 g, 0.91 mmol), BOC20 (0. 22 g, 1.1 eq), and DMAP (0.13 g, 1.1 eq. ) in dioxane (10 mL) was stirred at room temperature 3 days. Additional BOC20 (0. 10g, 0.5 eq. ) was added and the reaction mixture was stirred 4 hours. The reaction mixture was concentrated in vacuo, diluted with saturated NaHC03 (15 mL), and extracted with CH2CI2 (2 x 100 mL). The combined organics were dried over Na2SO4, filtered, and concentrated under reduce pressure. The crude product was purified by flash chromatography using a 5% (10% NH40H in MeOH) solution in CH2CI2 as eluent (0.35 g, 91 % yield). LCMS : MH+= 420.

PREPARATIVE EXAMPLE 193:

By essentially the same procedure set forth in Preparative Example 192 only substituting the compound prepared in Preparative Example 183, the above compound was prepared. MS: MH* = 360.

PREPARATIVE EXAMPLE 193.10 : By essentially the same procedure set forth in Preparative Example 192 only substituting the compound prepared in Preparative Example 184.1, the above compound was prepared. MS: MH+ = 454.

PREPARATIVE EXAMPLE 194:

By essentially the same procedure set forth in Preparative Example 192 only substituting the above compound prepared in Preparative Example 187. 11, the above compound was prepared (0.223 g, 88% yield). MS: MH+ = 528.

PREPARATIVE EXAMPLE 195:

By essentially the same procedure set forth in Preparative Example 127 only substituting the compound prepared in Preparative Example 192, the above compound was prepared (0.38 g, 95% yield). LCMS: MH+= 498.

PREPARATIVE EXAMPLE 196: By essentially the same procedure set forth in Preparative Example 195, only substituting the compound prepared in Preparative Example 193, the above compound was prepared (0.3 g, 83% yield). MS: MH+ = 438.

PREPARATIVE EXAMPLE 197:

A solution of the compound prepared in Preparative Example 195 (0.15 g, 0.3 mmol), phenylboronic acid (0.073 g, 2.0 eq. ), K3PO4 (0. 19 g, 3.0 eq. ), and Pd (PPh3) 4 (0.017 g, 5 mol %) was heated at reflux in DME (16 mL) and H20 (4 mL) 7 hours. The resulting solution was cooled to room temperature, diluted with H20 (10 mL), and extracted with CH2CI2 (3 x 50 mL). The combined organics were dried over Na2SO4, filtered, and concentrated. The crude product was purified by flash chromatography using a 2.5% (10% NH40H in MeOH) in CH2CI2 solution as eluent (0.16 g, 100% yield).

PREPARATIVE EXAMPLE 198 : To a solution of 4-aminomethylpyridine (1.41 mL, 13.87 mmol) in CH2CI2 (50 mL) was added BOC20 (3.3 g, 1.1 eq. ) and TEA and the resulting solution was stirred a room temperature 2 hours. The reaction mixture was diluted with H20 (50 mL) and extracted with CH2CI2. The combined organics were dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by flash chromatography using a 5% (10% NH40H in MeOH) solution in CH2CI2 as eluent to give a yellow solid (2.62 g, 91 % yield). LCMS: MH+= 209.

PREPARATIVE EXAMPLE 199:

By essentially the same procedure set forth in Preparative Example 198 only substituting 3-aminomethylpyridine, the above compound was prepared as a yellow oil (2.66 g, 92% yield). LCMS: MH+= 209.

PREPARATIVE EXAMPLE 200: To a solution of the compound prepared in Preparative Example 198 (0.20 g, 0.96 mmol) in CH2CI2 (5 mL) at 0°C was added m-CPBA (0.17 g, 1.0 eq) and the resulting solution stirred at 0°C 2 hours and stored at 4°C overnight at which time the reaction mixture was warmed to room temperature and stirred 3 hours. The reaction mixture was diluted with H20 and extracted with CH2CI2.

The combined organics were dried over Na2S04, filtered, and concentrated. The crude product was purified by flash chromatography using a 10% (10% NH40H in MeOH) solution as eluent : LCMS: MH+= 255.

PREPARATIVE EXAMPLE 201: A solution of oxone (58.6 g) in H20 (250 mL) was added dropwise to the compound prepared in Preparative Example 199 (27 g, 0. 13 mol) and NaHC03 (21.8 g, 2.0 eq. ) in MeOH (200 mL) and H20 (250 mL). The resulting solution was stirred at room temperature overnight. The reaction mixture was diluted with CH2CI2 (500 mL) and filtered. The layers were separated and the aqueous layer extracted with CH2CI2. The combined organics were dried over Na2SO4, filtered, and concentrated under reduced pressure to give a white solid (21.0 g, 72% yield). MS: MH+= 255.

PREPARATIVE EXAMPLE 202:

The compound prepared in Preparative Example 200 (0.29 g, 1.29 mmol) was stirred at room temperature in 4M HCI in dioxane (0.97 mL) 2 hours. The reaction mixture was concentrated in vacuo and used without further purification.

LCMS: MH+= 125.

PREPARATIVE EXAMPLE 203: By essentially the same procedure set forth in Preparative Example 202 only substituting the compound prepared in Preparative Example 201, the compound shown above was prepared. LCMS: MH+= 125.

PREPARATIVE EXAMPLE 204: To 4-N-t-Butoxycarbonylaminopiperidine (0.8 g, 4.0 mmol) in CH2CI2 (10 mL) at 0°C was added TEA (1.40 mL, 2.5 eq. ) and 3-trifluoromethyl benzoyl chloride (1.05 g, 1.25 eq. ). The resulting solution was stirred 15 minutes and warmed to room temperature and stirred 3 hours. The reaction mixture was diluted with CH2CI2 and washed with 5% Na2CO3 (2 x 100 mL). The organic layer was dried over Na2SO4, filtered and concentrated to yield a pale yellow solid (quantitative crude yield).

PREPARATIVE EXAMPLE 205 :

To a solution of the compound prepared in Preparative Example 204 (1.0 g, 2.76 mmol) in CH2CI2 (15 mL) at 0°C was added TFA (8 mL) and the resulting solution was stirred at 0°C for 30 minutes and room temperature 1 hour. The reaction mixture was poured onto Na2CO3 (40 g) and H20 (400 mL) added and the resulting mixture was extracted with CH2CI2. The combined organics were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by flash chromatography using a 20% (7N NH3 in MeOH) solution in CH2CI2 as eluent (0.6 g, 82% yield).

PREPARATIVE EXAMPLES 206: 0 0 STEP A H2N H2N STY OU H2N-"a step B 2 HCINN H STEP A: To a solution of 6-chloronicotinamide (1g, 6.39 mmol) in isoamyl alcohol (15 mL) at rt was added Na2CO3 (0. 81 g, 7.67 mmol) followed by methoxyethylamine (0.67 mL, 7.67 mmol). The mixture was heat at 130 °C for 16h, cooled to rt, and was filtered thru a medium glass-fritted filter. The resulting filtrate was concentrated under reduced pressure and the resultant solid was triturated with Et20 (2 x 10 mL). The crude solid was placed under high vacuum to afford 1.2 g (96%) of a light yellow solid. M+H = 196.

STEP B:

To a solution of amide (1.2 g, 6.12 mmol) from Preparative Example 206, Step A in THF (5 mL) at 0 °C was added a solution of BH3-THF (43 mL; 43 mmol) dropwise over 10 min. The resultant solution was warmed to rt and stirred for 14 h. The mixture was cooled to 0 °C and was sequentially treated with 6M HCI (35 mL), water (30 mL), and MeOH (150 mL). The mixture was stirred for 8 h and was concentrated under reduced pressure. The crude residue was triturated with MeOH, concentrated under reduced pressure, and placed under high vacuum to afford 1.6 g (82%) of a white solid as the dihydrochloride salt. M+H (free base) = 182. 0. This material was used crude in the coupling with 7-CI adducts.

PREPARATIVE EXAMPLES 207-211: By essentially the same known procedure set forth in Preparative Example 206 only by utilizing the amines shown in Column 2 of Table 13 and the amines shown in Column 3 of Table 13 were prepared: TABLE 13 Prep. Ex. Column 2 Column 3 CMPD (Amine) (Amine) M+H (free base) M+H = 138 207 H2Nz H2N< 2 HCI N N 208 HN H2N t H M+H = 152 -2 HCI N N 209 H2 M+H 178 N -2 HCI ZON NEZ 210 H2N M+H 195 H2N~Ns 3 HO HCI H 211 H N-H2N I M+H = 207 3 HCI N N ON", PREPARATIVE EXAMPLE 212: The above compound was prepared accordingly to the methods described in WO 91/18904.

PREPARATIVE EXAMPLE 213: The above compound was prepared accordingly to the methods described in US 6,180, 627 B 1.

PREPARATIVE EXAMPLE 214: The known amine was prepared as described in J. Med. Chem. (2001), 44,4505-4508.

PREPARATIVE EXAMPLE 215 : The known amine was prepared as described in J. Med. Chem. (1997), 40, 3726-3733.

PREPARATIVE EXAMPLE 216: OHC. , STEPA HON STEPB NNH N NH2 nu2 CI<N STEP C H2NtN . lui N NH2 N NHZ NH2 N NH2 STEP A :

A solution of aldehyde (50 g, 0.41 mol) [WO 0232893] in MeOH (300 mL) was cooled to 0 °C and carefully treated with NaBH4 (20g, 0.53 mol in 6 batches) over 20 minutes. The reaction was then allowed to warm to 20 °C and was stirred for 4 hours. The mixture was again cooled to 0 °C, carefully quenched with saturated aqueous NH4CI, and concentrated. Flash chromatography (5- 10% 7N NH3-MeOH/CH2CI2) provided the primary alcohol (31 g, 62%) as a light yellow solid.

STEP B: A slurry of alcohol (31 g, 0.25 mol) from Preparative Example 216, Step A in CH2CI2 (500 mL) was cooled to 0 °C and slowly treated with SOC12 (55mL, 0.74 mol over 30 minutes). The reaction was then stirred overnight at 20 °C.

The material was concentrated, slurried in acetone, and then filtered. The resulting beige solid was dried overnight in vacuo (38.4g, 52%, HCI salt).

STEP C: To a 15 mL pressure tube charged with a stir bar was added chloride (150 mg, 0.83 mmol) from Preparative Example 216, Step B followed by 7 M NH3/MeOH (10 mL). The resulting solution was stirred for 48 h at rt where upon the mixture was concentrated under reduced pressure to afford a light yellow solid (0.146 g, 83%). M+H (free base) = 140.

PREPARATIVE EXAMPLE 217: The above compound was prepared accordingly to methods described in WO 00/26210.

PREPARATIVE EXAMPLE 218: The above compound was prepared accordingly to methods described in WO 99/10325.

PREPARATIVE EXAMPLE 219:

The known amine dihydrochloride was prepared according to methods described in WO 02/64211.

PREPARATIVE EXAMPLE 220: The above compound was prepared according to methods described in WO 02/64211.

PREPARATIVE EXAMPLE 221: The known primary alcohol was prepared according to WO 00/37473 and was converted to the desired amine dihydrochloride in analogous fashion as Preparative Example 220 according to WO 02/064211.

PREPARATIVE EXAMPLE 222: H OH \ STEPA > STEP B N NHBoc N NHBoc Cl NH2 HUI STEP C N NHBoc N NHBoc STEP A: To a solution of aldehyde (WO 02/32893) (0.46 g, 2. 07 mmol) in MeOH/THF (2 mL/2 mL) at 0 °C was added NaBH4 (94 mg, 2.48 mmol) in one portion. The resulting mixture was stirred for 12 h at rt and was diluted with sat.

aq. NH4CI (3 mL). The mixture was concentrated under reduced pressure and the resultant aqueous layer was extracted with CH2CI2 (3 x 5 mL). The organic layers were combined, washed with brine (1 x 5 mL), dried (Na2SO4), and filtered. The organic layer was concentrated under reduced pressure to afford 417 mg (90% yield) of a white solid. M+H = 225.

STEP B: The crude alcohol from Preparative Example 222, step A (0.4 g, 1.78 mmol) in CH2CI2 (4 mL) was added SOCI2 (0.65 mL, 8.91 mmol) and the mixture was stirred for 2 h at rt. The mixture was concentrated under reduced pressure to afford 407 mg (94%) of a light yellow solid. M+H = 243. The crude product was taken on without further purification.

STEP C: To a solution of crude chloride from Preparative Example 222, Step B (0.33 g, 1.36 mmol) in a pressure tube charged with 7M NH3/MeOH (35 mL) and the mixture was stirred for 72 h. The mixture was concentrated under reduced pressure to afford 257 mg (85%) of a yellow semisolid. M+H (free base) = 224.

PREPARATIVE EXAMPLE 223: To a round bottom flask charged with amine hydrochloride (0.24 g, 1.1 mmol) from Preparative Example 222 and a stir bar was added 4N HCI/dioxane (10 mL). The resulting solution was stirred for 12h at rt, concentrated under reduced pressure, and triturated with CH2CI2 (3 x 5 mL). The crude product was filtered, washed with Et20 (2 x 5mL), and dried under high vacuum to afford 0.19g (91%) as the dihydrochloride salt. M+H (free base) = 124.

PREPARATIVE EXAMPLE 224:

Pd (PPh3) 4 (0.404 gm, 0.35 mmol) was added to a degassed solution of 4-cyanobenzene boronic acid (1.029 g, 7 mmol) and 2-bromopyridine (1. 11 g, 7 mmol) in 75 mL acetonitrile. 0.4 M sodium carbonate solution (35 mL) was added to the reaction mixture and the resulting solution was refluxed at 90°C under Ar for 24 hours (progress of reaction was monitored by TLC). The reaction mixture was cooled and aqueous layer was separated. The organic layer containing the product and spent catalyst was mixed with silica gel (15 g) and concentrated to dryness. The 4- (2-pyridyl)-benzonitrile was isolated by column chromatography (0.850 g, 68%). LCMS: MH+ = 181 ; 1H NMR (CDCI3) 6 8.85 (d, 1H), 8.7 (dd, 1H), 7.9 (dd, 1H), 7.75 (d, 2H), 7.7 (d, 2H), 7.4 (dd, 1H).

PREPARATIVE EXAMPLES 225-228: By following essentially same procedure described in Preparative Example 224, only substituting the bromides in column 2 of Table 14, compounds in column 3 of Table 14 were prepared.

Table 14 Prep. Column 2 Column 3 Column 4 Ex. 225 Br CN Yield = 70% NS LCMS : MH+ = 187 \--i I NS \--i 226 Br CN Yield = 60% N"'S W LCMS : MH+ = 187 U NS N S 227 Br CN Yield = 70% 6 1 LCMS : MH4= 186 vs S 228 S CN Yield = 70% LCMS : MH+ = 200 Mu Br Me \ S PREPARATIVE EXAMPLE 229:

BH3-THF solution (1 M, 24 mL, b eq) was added slowly to a stirring solution of 4- (2-pyridyl)-benzonitrile (0.85 g, 4.72 mmol) in anhydrous THF (25 mL) under Ar, and the resulting solution was refluxed for about 12 hr. The solution was cooled to 0°C using ice-water. Methanol (15 mL) was added drop- wise to the cold reaction mixture and stirred for 1 h to destroy excess BH3.

Added HCI-methanol (1 M, 10 mL) slowly to the reaction mixture and refluxed for 5 h. Concentrated the solution to dryness and the residue was dissolved in 25 mL water and extracted with ether to remove any un-reacted material. The aqueous solution was neutralized with solid potassium carbonate to pH 10-11.

The free amine, thus formed was extracted with ether, dried over potassium carbonate (0. 45 g, 50%). LCMS: MH+ = 185; 1H NMR (CDCl3) # 8. 85 (d, 1H), 8.7 (dd, 1 H), 7.9 (dd, 1 H), 7.75 (d, 2H), 7.7 (d, 2H), 7.4 (dd, 1 H), 3.7 (t, 2H), 1.7 (t, 2H).

PREPARATIVE EXAMPLES 230-233: By following essentially the same procedure set forth in Preparative Example 229, compounds in column 3 of Table 15 were prepared.

Table 15 Prep. Column 2 Column 3 Column 4 Ex. 230 CN CH2NH2 Yield = 60% LCMS : MH+= 191 N s N s CN CH2NH2 Yield = 60% LCMS : MH+= 191 N s N s \===/\=/ 232 CN CH2NH2 Yield = 70% LCMS : MH+= 190 s s 233 CN CH2NH2 Yield = 7% LCMS : MH+= 204 Me Me % % PREPARATIVE EXAMPLE 234:

Step A: A mixture 4-fluorobenzonitrile (3 g, 25 mmol) and imidazolyl sodium (2.48 g, 27.5 mmol) in DMF (50 mL) was stirred at 80°C under Ar for 12 h. Progress of reaction was monitored by TLC. The reaction mixture was concentrated in vacuo and the residue was diluted with 50 mL water and stirred. The aqueous mixture was extracted with EtOAc (2 x 50 mL). Combined EtOAc extracts was dried over

anhydrous MgS04, concentrated, and the 4- (1-imidazolyl)-benzonitrile was isolated by column chromatography (3.6 g, 78%). LCMS: MH+ = 170 ;'H NMR (CDC13) 8 8.0 (s, 1 H), 7.5 (d, 2H), 7.4 (m, 3H), 7.3 (d, 1 H) Step B: 4- (1-imidazolyl)-benzonitrile (1g, 5.92 mmol) was dissolved in anhydrous THF (10 mL) and added drop-wise to a stirring solution of LAH-THF (1 M in THF, 18 mL) at room temperature. The reaction mixture was refluxed under Ar for 2 h and the progress was monitored by TLC. The mixture was cooled to 0°C and quenched by drop-wise addition of a saturated Na2S04-H20 solution. The mixture was stirred for 1 h and filtered to remove lithium salts. The filtrate was dried over anhydrous MgS04 and concentrated to obtain 4- (1-imidazolyl)- benzylamine (0.8 g, 80%). LCMS: MH+ = 174.

PREPARATIVE EXAMPLE 235: A mixture of 4- (5-oxazolyl) benzoic acid (1.0 g, 5.46 mmol) and Et3N (552 mg, 5.46 mmol) in 25 mL of THF was cooled to 0 °C and CICOOi-Bu (745 mg, 5.46 mmol) was added dropwise. After the addition was over, the reaction mixture was stirred for additional 5 min and then aq NH40H (0.63 mL of 28% solution, 10.46 mmol) was added. After overnight stirring, the solvent was evaporated, the residue was taken up in water and basified to pH 9. The precipitated solid was filtered, washed with water and dried over ? 205 in a vacuum desiccator to provide 500 mg (48%) of the 4- (5-oxazolyl)-benzamide :'H NMR (DMSO-d6) 8 8.50 (s, 1 H), 8.20-7. 80 (m, 5H).

PREPARATIVE EXAMPLE 236:

A suspension of 4- (5-oxazolyl) benzamide (500 mg, 2.657 mmol) in 10 mL of dry THF was cooled to 0 °C and 10 mL of 1 M BH3. THF (10.00 mmol) was added. The contents were refluxed overnight and the excess borane was destroyed by dropwise addition of methanol. The solvent was evaporated and the residue was treated with methanolic HCI to decompose the amine-borane complex. After evaporation of the methanol, the residue was taken in water, basified to pH 10 and the product was extracted in to DCM. The DCM layer was dried (K2CO3) and the solvent was removed to provide 150 mg (32%) of 4- (5- oxazolyl) benzylamine :'H NMR (CDC13) 8 7.90 (s, 1H), 7.60 (d, 2H), 7. 40 (d, 2H), 7.30 (s, 1 H), 3.90 (s, 2H).

PREPARATIVE EXAMPLES 237-239: By essentially the same procedures set forth above, the compounds in Column 2 of Table 16 were reduced using the method indicated in Column 3 of Table 16 to give the amine indicated in Column 4 of Table 16.

Table 16 Prep. Column 2 Column 3 Column 4 CMPD Ex. 237 CN BH3 0"'H NMR W H2N /C2 (CDCI3) 0 7. 15-6. 90 (m, 3H), O 3. 85 (s, 2H), su 1. 45 (s, 2H) F 238 CN H2 Me'H NMR (CDC3) 5 f 1 H2N vN 8. 40 (s, 1 H), Nsv. 7. 55 (dd, 1 H), 7. 10 (d, Me 1 H), 3. 85 (s, 2H), 2. 50 (s, 3H), 1. 70 (bs, 2 H) 239 CN BH3,, Me , v. e Nz Mu Me PREPARATIVE EXAMPLE 240

Prepared by the literature procedure (PCT Int. Appl, WO 0105783) :'H NMR (CD3) # 7. 35 (d, 1 H), 7.24-7. 10 (m, 2 H), 7.02 (d, 1 H), 3.95 (t, 1 H), 3.70 (d, 1 H), 3.37 (d, 1 H), 2.65 (m, 2H), 2.45 (s, 3H), 1.90 (bs, 2H) PREPARATIVE EXAMPLE 241: 3- (AMINOMETHYL) PIPERIDINE-1-CARBOXAMIDE A. 3- (tert-BUTOXYCARBONYLAMINOMETHYL) PIPERIDINE-1- CARBOXAMIDE 3 (R/S)- (tert-Butoxycarbonylaminomethyl) piperidine (3g, 14. Ommoles) was dissolved in anhydrous dichloromethane (50mL) and trimethylsilylisocyanate (9.68g, 11.4mL, 84. Ommoles) was added. The mixture was stirred under argon at 25°C for 68h. Additional trimethylsilylisocyanate (4.84g, 5.7mL, 42. Ommoles) was added and the mixture was stirred at 25°C for a total of 90h. The mixture was evaporated to dryness and chromatographed on a silica gel column (30x5cm) using 2% (10% conc. ammonium hydroxide in methanol)- dichloromethane as the eluant to give 3- (tert-

butoxycarbonylaminomethyl) piperidine-1-carboxamide (3.05g, 85%): FABMS: m/z 258.1 (MH+) ; HRFABMS: m/z 258.1816 (MH+). Calcd. for C12H2403N3 : m/z 258.1818 ; aH (CDCI3) 1. 22 91 H, m, CH2), 1.42 (9H, s, -COOC (CH3) 3), 1.48 (1H, m, CH2), 1.67 (2H, m, CH2), 1.78 (1 H, m, CH), 2.80 (1 H, m, CH2), 2.99, 3H, m, CH2), 3.59 (1 H, m, CH20 3.69 (1 H, m, CH2), 4.76 (2H, bm, CONH2) and 4.98ppm (1H, bm, NH); 8c (CDC13) CH3 : 28.5, 28.5, 28.5 ; CH2: 24.0, 28.3, 43.2, 45.1, 47.8 ; CH: 36.5 ; C: 79.4, 156.3, 158.5.

B. 3- (AMINOMETHYL) PIPERIDINE-1-CARBOXAMIDE 3-(teff-Butoxycarbonylaminomethyl) piperidine-1-carboxamide (150mg, 0. 583mmoles) (prepared as described in Preparative Example 241, Step A above) was dissolved in methanol (3mL). 10% conc. sulfuric acid in 1,4-dioxane (7.9mL) was added and the mixture was stirred at 25°C for 1 h. The mixture was diluted with methanol and BioRad AG1-X8 resin (OH'form) was added until the pH was basic. The resin was filtered off, washed with methanol, evaporated to dryness and chromatographed on a silica gel column (15x2cm) using dichloromethane followed by 15% (10% conc, ammonium hydroxide in methanol)-dichloromethane as the eluant to give the 3-(aminomethyl) piperidine- 1-carboxamide (80mg, 87%): FABMS: m/z 158.1 (MH+) ; HRFABMS: m/z 158.1294 (MH+). Calcd. for C7H16N3O : m/z 158.1293 ; 8H (CDC13 + drop CD30D) 1.20 (1 H, m, CH2), 1. 48 (1 H, m, CH2), 1.60 (1H, m, CH), 1. 68 (1 H, m, CH2), 1.83 (1 H, m, CH2), 2.64 (bm, 2H,-CH2NH2), 2.82 (1 H, m, CH2), 3.02 (1 H, m, CH2), 2.98 (2H, m, CH2), 3.70 (1 H, m,-CH2NH2), 3.78 (1 H, m, -CH2NH2) and 5.24 ppm (1H, bs, NH); bc (CDC13 + drop CD30D) CH2: 24.1, 28.6, 44.0, 44. 8, 47.9 ; CH: 38.3 ; C: 159.0.

PREPARATIVE EXAMPLE 242: 3-(2-AMINOETHYL)PIPERIDINE-1-CARBOXAMIDE A. 3-(2-tert-BUTOXYCARBONYLAMI NOETHYL) PI PERI Dl NE-1- CARBOXAM I DE

3- (2-tert-Butoxycarbonylaminoethyl) piperidine (500rng, 2. 19mmoles) was dissolved in anhydrous dichloromethane (10mL) and trimethylsilylisocyanate (2.96mL, 21. 9mmoles) was added. The mixture was stirred under argon at 25°C for 3.35h. The mixture was diluted with dichloromethane and washed with saturated aqueous sodium bicarbonate. The organic layer was dried (MgSO4), filtered, evaporated to dryness and chromatographed on a silica gel column (15x5cm) using 5% (10% conc. ammonium hydroxide in methanol)- dichloromethane as the eluant to give 3- (2-tert- butoxycarbonylaminoethyl) piperidine-1-carboxamide (417.7mg, 70%): FABMS: m/z 272.0 (MH+) ; HRFABMS: m/z 272.1979 (MH+). Calcd. for C13H2603 : m/z 272.1974 ; 5H (CDC13) 1.16 (1H, m, CH2), 1-30-1.60 (5H, m, CH/CH2), 1.46 (9H, s, -COOC (CH3) 3), 1. 68 (1H, m, CH2), 1 84 (1H, m, CH2), 2.54 (1H, dd, CH2), 2.73 (1H, m, CH2), 3.08 (1H, m, CH2), 3.42 (1H, m, CH2), 4.02 (1H, m, CH2), 4.10 (1 H, m, CH2), 4.84 (1 H, m, NH) and 4.96 ppm (2H, bm, CONH2) ; 8c (CDCl3) CH3 : 28.5, 28.5, 28.5 ; CH2 : 25.2, 31.7, 34.9, 37.3, 44.6, 50.3 ; CH: 32.9 ; C: 79.5, 156.4, 158.2.

B. 3- (2-AMINOETHYL) PIPERIDINE-1-CARBOXAMIDE 3-(2-teff-Butoxycarbonylaminoethyl) piperidine-1-carboxamide (392.7mg, 1. 45mmoles) (prepared as described in Preparative Example 242, Step A above) was dissolved in methanol (7.5mL) and 10% conc. sulfuric acid in 1,4-dioxane (19. 5mL) was added. The mixture was stirred at 25°C for 1.25h. The mixture was

diluted with methanol and BioRad AG1-X8 resin (OH'form) was added until the pH was basic. The resin was filtered off, washed with methanol, evaporated to dryness and chromatographed on a silica gel column (30x2.5cm) using 15% (10% conc, ammonium hydroxide in methanol)-dichloromethane as the eluant to give 3-(2-aminoethyl) piperidine-1-carboxamide (233mg, 94%): FABMS: m/z 172.1 (MH+) ; HRFABMS: m/z 172.1444 (MH+). Calcd for C8H18N3O requires: m/z 172.1450 ; 8H (CDCl3 + 3% CD30D) 1.14 (1H, m, CH2), 1.40 (2H, m, CH2), 1.49 (1 H, m, CH), 1.58 (1 H, m, CH2), 1.69 (1 H, m, CH2), 1.85 (1 H, m, CH2), 2.55 (1 H, m, CH2), 2.67 (5H, m, CH2/NH2), 2.76 (1 H, bm, CH2), 2.84 (1 H, m, CH2) and 3.82 ppm (2H, m, CONH2) ; âc (CDC13 + 3% CD30D) CH2: 24.8, 30.9, 36.6, 38.9, 44.9, 50.0 ; CH: 33.4.

PREPARATIVE EXAMPLE 243: 4- (2-AMINOETHYL) PI PERIDI NE-1-CARBOXAM I DE

A. 4- (2-tert-BUTOXYCARBONYLAMINOETHYL) PIPERIDINE-1- CARBOXAMIDE

4- (2-tert-Butoxycarbonylaminoethyl) piperidine (500mg, 2. 19mmoles) was dissolved in anhydrous dichloromethane (10mL) and trimethylsilylisocyanate (2.96mL, 21. 9mmoles) was added. The mixture was stirred under argon at 25°C for 3.25h. The mixture was diluted with dichloromethane and washed with saturated aqueous sodium bicarbonate. The organic layer was dried (MgS04), filtered, evaporated to dryness and chromatographed on a silica gel column (15x5cm) using 5% (10% conc. ammonium hydroxide in methanol)- dichloromethane as the eluant to give 4- (2-terl= butoxycarbonylaminoethyl) piperidine-1-carboxamide (308.2mg, 52%): FABMS:

m/z 272.0 (MH+) ; HRFABMS: m/z 272.1965 (MH+). Calcd. for C13H2603N3 : m/z 272.1974 ; 8H (CDC13) 1.20 (2H, m, CH2), 1.47 (9H, s,-COOC (CH3) 3), 1.45-1. 55 (3H, m, CH/CH2), 1.75 (2H, m, CH2), 2.82 (2H, m, CH2), 3.19 (2H, m, CH2), 3.96 (2H, m, CH2), 4.64 (2H, m, CH2) and 4.70 ppm (1 H, bm, NH); 8c (CDC13) CH3 : 28. 5,28. 5,28. 5; CH2: 31.8, 31.8, 36.7, 38.0, 44.5, 44.5 ; CH: 33.4 ; C: 79.2, 156.7, 158. 1.

A. 3- (2-AMINOETHYL) PIPERIDI NE-1-CARBOXAMIDE 4-(2-tert-Butoxycarbonylaminoethyl) piperidine-1-carboxamide (283.3mg, 1. 04mmoles) (prepared as described in Preparative Example 243, Step A above) was dissolved in methanol (5.4mL) and 10% conc. sulfuric acid in 1,4-dioxane (14.2mL) was added and the mixture was stirred at 25°C for 1.25h. The mixture was diluted with methanol and BioRad AG1-X8 resin (OH'form) was added until the pH was basic. The resin was filtered off, washed with methanol, evaporated to dryness and chromatographed on a silica gel column (30x2.5cm) using 15% (10% cone, ammonium hydroxide in methanol)-dichloromethane as the eluant to give the 3-(2-aminoethyl) piperidine-1-carboxamide (170mg, 95%): FABMS: m/z 172.1 (MH+) ; HRFABMS: m/z 172.1442. Calcd for C8H18N3O requires: m/z 172.1450 ; 8H (CDC13 + 3% CD30D) 1.16 (2H, m, CH2), 1.43 (2H, m, CH2), 1.52 (1 H, m, CH), 1.70 (2H, m, CH2), 2.70-2. 85 (8H, m, CH2) and 3.92 ppm (2H, m, CONH2); 8c (CDC13 + 3% CD30D) CH2: 31.9, 31.9, 39.0, 39.7, 44.4, 44.4 ; CH: 33.5 ; C: 158.7.

PREPARATIVE EXAMPLE 244: 3- (AMINOMETHYL)-l-METHYLPIPERIDINE A. 3-(BROMOMETHYL)-1-METHYLPIPERIDINE

3-(Hydroxymethyl)-1-methylpiperidine (2g, 15. 5mmoles) was dissolved in anhydrous acetonitrile (32mL) and anhydrous pyridine (2.02mL, 24. 8mmoles) was added and the solution was cooled to 0°C. Dibromotriphenylphosphorane (8.49g, 20. 2mmoles) was added at 0°C and the mixture was allowed to warm up to 25°C and was stirred for 94h. The mixture was evaporated to dryness and the residue was chromatographed on a silica gel column (30x5cm) using gradient elution with dichloromethane, 35% diethyl ether in dichloromethane and 5-10% methanol in dichloromethane as the eluant to give 3-(bromomethyl)-1- methylpiperidine (3.13g, 100%): FABMS: m/z 192.1 (MH+) ; 8H (CDC13) 1.52 (1H, m, CH2), 1.99 (2H, m, CH2), 2.43 (1 H, m, CH2), 2.75 (2H, m, CH2), 2. 82 (1 H, m, CH), 2.86/2. 88 (3H, s, NCH3), 3.42/3. 49 (2H, dd,-CH2Br) and 3.56 ppm (2H, m, CH2); bc (CDCI3) CH3 : 44.3 ; CH2 : 22.1, 26.6, 35.4, 54.8, 58.2 ; CH: 34.6.

A. 3-(Di-tert-BUTOXYCARBONYLAMINOMETHYL)-1-METHYLPIPERIDINE 3-(Bromomethyl)-1-methylpiperidine (1.5g, 7. 81 mmoles) (from Preparative Example 244, Step A above) and di-tert-butyliminodicarboxylate (1.697g, 7. 81 mmoles) were dissolved in anhydrous acetonitrile (25mL). Cesium carbonate (5. 1g, 15. 6mmoles) and lithium iodide (52mg, 0. 391 mmoles) were added and the mixture was stirred at 70°C for 20h. The mixture was evaporated to dryness and the residue was partitioned between dichloromethane and saturated aqueous sodium bicarbonate. The organic layer was dried (MgS04), filtered and evaporated to dryness. the residue was chromatographed on a silica gel column (30x5cm) using 3% methanol in dichloromethane as the eluant to

give 3-(di-teff-butoxycarbonylamino)-1-methylpiperidine (1. 331g, 52%): FABMS: m/z 329.2 (MH+) ; HRFABMS: m/z 329.2438 (MH+). Calcd. for C17H33N204 : m/z 329.2440 ; zu (CDC13) 1.10 (1H, m, CH2), 1.54 (18H, s, -COOC (CH3) 3), 1.86 (2H, m, CH2), 2.01 (1H, m, CH2), 2.19 (1H m, CH), 2.34 (2H, bm, CH2), 2.59 (3H, - NCH3), 3.19 (2H, m, CH2) and 3.52/3. 52 ppm (2H, -CH2N-) ; 8c (CDCI3) CH3 : 28.5, 28.5, 28.5, 28.5, 28. 5,28. 5,47. 2; CH2: 25.4, 28.3, 50.4, 56.8, 60.8 ; CH: 37.2 ; C: 83.0, 83.0, 153.5, 153.5.

A. 3- (AMINOMETHYL)-1-METHYLPIPERI DINE 3-(Di-tert-butoxycarbonylamino)-1-methylpiperidine (500mg, 1. 52mmoles) (from Preparative Example 244, Step B above) was dissolved in methanol (7.5mL) and 10% (v/v) conc. sulfuric acid in 1,4-dioxane (19. 75mL) was added.

The solution was stirred at 25°C for 0.5h. Methanol (300mL) was added, followed by BioRad AG1-X8 resin (OH-form) until the pH was-10. The resin was filtered off and washed with methanol (2x200mL). The combined eluates were evaporated to dryness and the residue was chromatographed on a silica gel column (30x2.5cm) using 10% (10% conc. ammonium hydroxide in methanol)-dichloromethane as the eluant to give 3-(aminomethyl)-1- methylpiperidine (69.2mg, 35%): FABMS: m/z 129.1 (MH+) ; HRFABMS: m/z 129.1392 (MH+). Calcd. for C7H17N2 : m/z 129.1392 ; 5H (CDC13) 0. 90 (2H, m, CH2), 1.65 (2H, m, CH2), 1.72 (1 H, m, CH), 1.79 (1 H, m, CH2), 1. 91 (1 H, m, CH2), 2.30 (3H, s,-NCH3), 2.64 (2H, m, CH2), 2.82 (1 H, m, -CH2NH2) and 2.92 <BR> <BR> <BR> <BR> ppm (1 H, m, -CH2NH2); 8c (CDC13) CH3 : 46.7 ; CH2: 25.2, 28.0, 46.3, 56.4, 60.3 ; CH: 39.9.

PREPARATIVE EXAMPLE 245: 4- (AMINOMETHYL)-1-METHYLPIPERIDINE A. 1-METHYLISONIPECOTAMIDE

Isonipecotamide (10g, 78. 0mmoles) was dissolved in distilled water (100mL) and 37% aqueous formaldehyde (7.6mL, equivalent to 2. 81g HCHO, 93. 6mmoles) was added. Wet 10% Pd-C (8 spoon spatulas) was added under argon and the mixture was hydrogenated at 25°C and 50psi for 43h. The catalyst was filtered off through Celite and the latter was washed with water and methanol. The combined filtrates were evaporated to dryness and the residue was chromatographed on a silica gel column (60x5cm) using 8%-10%-20% (10% conc. ammonium hydroxide in methanol)-dichloromethane as the eluant to give 1-methylisonipecotamide (7.15g, 64%): FABMS: m/z 143.1 (MH+) ; HRFABMS: m/z 143.1184 (MH+). Calcd. for C7H1sN2O : m/z 143.1184 ; 8H (d6- DMSO) 1.50/1. 57 (4H, m, CH2), 1.76/1. 94 (4H, m, CH2), 2.10 (3H, s,-NCH3), 2.72 (1H, m, CH) and 6.68/7. 18 ppm (2H, m, CONH2) ; 5c (d6-DMSO) CH3 : 41.2 ; CH2: 28.5, 28.5, 54.9, 54.9 ; CH: 46.2 ; C: 176.7.

B. 4- (AMINOMETHYL)-1-METHYLPIPERIDINE 1-Methylisonipecotamide (6.75g, 47. 5mmoles) (prepared as described in Preparative Example 245, Step A above) was dissolved in anhydrous THF (350mL) and the resulting mixture was added in portions to a stirred slurry of lithium aluminum hydride (1.8g, 47. 5mmoles) in anhydrous THF (100mL) at 0°C under nitrogen. The mixture was stirred at 0°C for 30min and then heated at 66°C for 25h under nitrogen. Distilled water (1.88mL) was added dropwise to the

stirred mixture at 0°C, followed by 20% aqueous sodium hydroxide (1.42mL) and then distilled water (6.75mL) and the mixture was stirred for 15min. The mixture was filtered and the solids were washed with THF and dichloromethane. The combined filtrates were evaporated to dryness and chromatographed on a silica gel column (30x5cm) using 15%-20% (10% conc. ammonium hydroxide in methanol)-dichloromethane as the eluant to give 4-(aminomethyl)-1- methylpiperidine (0.678g, 11%) : FABMS: m/z 129.1 (MH+) ; HRFABMS: m/z 129.1389 (MH+). Calcd. for C7H17N2 : m/z 129.1392 ; Sn (d6-DMSO) : 2.08ppm (3H, s,-NCH3) ; bc (d6-DMSO) : CH3 : under DMSO peaks; CH2: 29.6, 29.6, 46.7, 55.2, 55.2 ; CH: 46.2.

PREPARATIVE EXAMPLE 246: 3- (AMINOMETHYL) BENZONITRILE A. 3- UTOXYCARBONYLAM I NO) BENZON ITRI LE 3- (Bromomethyl) benzonitrile (5g, 25. 5mmoles) and di-tert- butyliminodicarboxylate (5.54g, 25. 5mmoles) were dissolved in anhydrous THF (50mL) and cesium carbonate (16.62g, 25. 5mmoles) and lithium iodide (170. 5mg, 1. 275mmoles) were added. The mixture was stirred at 70°C for 22h and the reaction was worked up as described in Preparative Example 89, Step B above. The residue was chromatographed on a silica gel column (60x5cm) using 5% ethyl acetate in hexane as the eluant to give 3- (di-tert- butoxycarbonylamino) benzonitrile (7.39g, 87%): FABMS: m/z 333.2 (MH+) ;

HRFABMS: m/z 333.1815 (MH+) ; Calcd. for C18H25N204 : m/z 333.1814 ; #H (CDC13) 1.52 (18H, s,-COOC (CH3) 3), 4.84 (2H, s, CH2), 7.48 (1H, m, Ar-H), 7.60 (2H, m, Ar-H) and 7.65 ppm (1H, m, Ar-H); 8c (CDC13) CH3 : 28.1, 28.1, 28.1, 28.1, 28. 1,28. 1; CH2: 48.4 ; CH: 129.2, 131.0, 131.0, 131.9 ; C: 83.2, 83.2, 112.5, 118.8, 140.1, 152.5, 152.5.

B. 3- (AMINOMETHYL) BENZONITRILE 3-(Di-tert-butoxycarbonylamino) benzonitrile (2g, 6. 0mmoles) (prepared as described in Preparative Example 246, Step A above) was dissolved in methanol (30mL) and 10% (v/v) (10% conc. sulfuric acid in 1,4-dioxane) (79mL) was added. The solution was stirred at 25°C for 0.25h and worked up as described in Preparative Example 89, Step C above). The residue was chromatographed on a silica gel column (15x5cm) using 3% (10% conc. ammonium hydroxide in methanol)-dichloromethane as the eluant to give the title compound (651.4mg, 82%): FABMS: m/z 133.1 (MH+) ; HRFABMS: m/z 133.0762 (MH+). Calcd. for C8H9N2 : m/z 133.0766 ; 8H (CDC13) 2.57 (2H, s,-CH2NH2), 3.92 (2H, s,- CH2NH2), 7.46 (1 H, m, Ar-H), 7.57 (2H, m, Ar-H) and 7.64 ppm (1 H, m, Ar-H); 8c (CDC13) CH2: 45.2 ; CH: 129.4, 130.7, 130.7, 131.8 ; C: 112.4, 118.8, 143.8.

PREPARATIVE EXAMPLE 247 : 4-(AMINOMETHYL)BENZONITRILE A. 3- (Di-tert-BUTOXYCARBONYLAMINOMETHYL) BENZONITRILE

4- (Bromomethyl) benzonitrile (5g, 25. 5mmoles) and di-tert- butyliminodicarboxylate (5.54g, 25. 5mmoles) were dissolved in anhydrous THF (50mL) and cesium carbonate (16. 62g, 25. 5mmoles) and lithium iodide (170. 5mg, 1. 275mmoles) were added. The mixture was stirred at 70°C for 23h and the reaction was worked up as described in Preparative Example 244, Step B above. The residue was chromatographed on a silica gel column (50x5cm) using 5% ethyl acetate in hexane as the eluant to give 4- (di-tert- butoxycarbonylaminomethyl) benzonitrile (7.07g, 83%): FABMS: m/z 333.2 (MH+) ; HRFABMS: m/z 333.1816 (MH+). Calcd. for C18H25N204 : m/z 333.1814 ; aH (CDC13) 1.45 (18H, s,-COOC (CH3) 3), 4.81 (2H, s, CH2), 7.37 (2H, d, Ar-H) and 7.62 ppm (2H, d, Ar-H); 8c (CDC13) CH3 : 28. 1,28. 1,28. 1,28. 1, 28. 1,28. 1; CH2: 49.2 ; CH: 127. 8, 127. 8, 132.3, 132.3 ; C: 83.2, 83.2, 111.1, 118.9, 144.1, 152.4, 152.4.

B. 4- (AMINOMETHYL) BENZONITRILE 4- (Di-tert-butoxycarbonylaminomethyl) benzonitrile (2g, 6. 0mmoles) (prepared as described in Preparative Example 247, Step A above) was dissolved in TFA (4mL) and the solution was stirred at 25°C for 0.25h. The

reaction mixture was diluted with dichloromethane and extracted with 1 N sodium hydroxide. The organic layer was dried (MgS04), filtered and evaporated to dryness. The residue was chromatographed on a silica gel column (15x5cm) using 3% (10% conc. ammonium hydroxide in methanol)-dichloromethane as the eluant to give 4- (aminomethyl) benzonitrile (108mg, 68%): FABMS: m/z 133.1 (MH+) ; HRFABMS: m/z133. 0764 (MH+). Calcd. for C8HgN2 : m/z 133.0766 ; 8H (CDCI3) 2.04 (2H, s, -CH2NH2), 3.89 (2H, s, -CH2NH2), 7.40 (2H, d, Ar-H) and 7.59 ppm (2H, d, Ar-H); bc (CDC13) CH2 : 45.7 ; CH: 127.8, 127.8, 132.4, 132.4 ; C: 110.6, 118.9, 148.0.

PREPARATIVE EXAMPLE 248 To a solution of (1 S, 2S)-2-benzyloxycyclopentyl amine (1.5 g, 7.84 mmol) in MeOH (50 mL) at rt was added 10 % Pd/C (50% wet, 1.0 g) followed by dropwise addition of conc. HCI (0.7 mL). The mixture was stirred under a balloon of H2 for 14 h and the catalyst was filtered off thru a pad of Celite. The pad of Celite was washed with MeOH (2 x 10 mL) and the resulting filtrate was concentrated under reduced pressure to afford 0.97 g (90%) of a yellow semisolid ; M+H (free base) = 102 PREPARATIVE EXAMPLES 249-251 In an analogous fashion to Preparative Example 248, the benzyl protected cycloalkyl amines (Column 2) were converted to the desired aminocycloalkanol hydrochloride derivatives (Column 3) as listed in Table 17.

TABLE 17 Ex. Column 2 Column 3 CMPD (Amine) (Cleavage method) M+H OBn NH2 249'''NH , M+H = 102 e-IINH2 (free base) 250 OBn OH M+H = 116 (free base) .,, NH2 NH2 HCI 251 OBn OH M+H = 116 (free base) NH NH-HCI PREPARATIVE EXAMPLE 252

To a solution of ester (prepared according to J. Org. Chem. (1999), 64, 330) (0.5 g, 2.43 mmol) in THF (8 mL) at 0 °C was added LiAIH4 (0.37 g, 9.74 mmol) in one portion. The resulting mixture was heated at reflux for 12h and was cooled to 0 °C. The mixture was treated sequentially with H2O (1 mL), 1 M NaOH (1 mL), and H20 (3 mL). CH2CI2 (10 ml) was added to the mixture which was stirred vigorously for 30 min. The mixture was filtered thru a pad of Celite which was washed generously with CH2CI2 (3 x 5 mL). The resulting filtrate was concentrated under reduced pressure to afford 0.41 g (85%) of a yellow/orange solid. M+H = 142.

PREPARATIVE EXAMPLE 253 MeO) o STEP A STEP B 0" TFA TFA HCI STEP C ,, /I H TFA OH H OH

STEP A: To a solution of L-proline methyl ester hydrochloride (0.50 g, 3.0 mmol) in CH2CI2 (15 mL) at 0 °C was added Et3N (1.1 mL, 7.55 mmol) followed by TFAA (0.56 mL, 3.92 mmol). The mixture was stirred for 12 h at rt and 1 N HCI (25 mL) was added. The layers were separated and the organic layer was washed sequentially with sat. aq. NaHC03 (1 x 25 mL), and brine (1 x 25 mL). The organic layer was dried (Na2SO4), filtered, and concentrated under reduced pressure to afford 0.72 g (100%) of a yellow oil. M+H = 226. The crude material was taken onto Step B without further purification.

STEP B: To a solution of the compound prepared in Preparative Example 253, Step A (0.68 g, 3.0 mmol) in THF (20 mL) at 0 °C was added MeMgl (5.1 mL, 3. 0M in Et20) dropwise over 10 min. The resulting solution was stirred for 16 h at rt whereupon the mixture was quenched by addition of sat. aq. NH4CI. The mixture was concentrated to dryness and the resultant residue was stirred with EtOAc (100 mL) for 45 min and filtered. The filtrate was concentrated under reduced pressure to afford 0.68g (100%) of a yellow/orange oil. M+H = 226.

The crude material was taken onto Step C without further purification.

STEP C: To a solution of the compound prepared in Preparative Example 253, Step B (0.68 g, 3.0 mmol) in MeOH (5 mL) was added a solution of KOH (0.68 g, 12.1 mmol) in MeOH (5 mL). The mixture was stirred at reflux for 12h and rt for 72h whereupon the mixture was concentrated to dryness. The crude residue was suspended in EtOAc (50 mL) and was stirred vigorously for 30 min and was filtered. This procedure was repeated 2X more and the resultant filtrate was concentrated under reduced pressure to afford 128 mg (33%) of a maroon/orange oil. M+H = 130. This material was used without purification in the subsequent coupling step.

PREPARATIVE EXAMPLE 254: The aldehyde was prepared according to the procedure of Gupton (J.

Heterocyclic Chem. (1991), 28,1281).

PREPARATIVE EXAMPLE 255 Using the aldehyde from Preparative Example 254, the procedure of Gupton (J. Heterocyclic Chem. (1991), 28,1281) was employed to prepare the title aldehyde.

PREPARATIVE EXAMPLE 256 The title aldehyde was prepared according to the procedure of Ragan et. al Synlett (2000), 8,1172-1174.

PREPARATIVE EXAMPLE 257

The reaction of known cyclopentyl guanidine hydrochloride (Org. Lett.

(2003), 5,1369-1372) under the conditions of Ragan (Synleit (2000), 8,1172- 1174) afforded the title aldehyde.

PREPARATIVE EXAMPLE 258 The title compound was prepared according to known literature Monatshefte fur Chemie (1973), 104, 1372-1382.

EXAMPLES EXAMPLE 1 : A solution of the product from Preparative Example 127 (0.27 g, 0.875 mmol), 4-aminomethylpyridine (0.12 g, 1.3 eq. ), and K2CO3 (0.24 g, 2 eq. ) in CH3CN (5 mL) was stirred at room temperature 48 hours. The reaction mixture was diluted with H20 and extracted with CH2CI2. The combined organics were dried over Na2SO4, filtered and concentrated. The crude product was purified by flash chromatography using a 4% MeOH in CH2CI2 solution as eluent (0.28 g, 93% yield). LCMS: MH+=380 ; mp= >205°C (dec).

EXAMPLES 2-210: By following essentially the same procedure set forth in Example 1 only substituting the chlorides shown in Column 2 of Table 18 and the amines shown in Column 3 of Table 18, the compounds in Column 4 of Table 18 were prepared: TABLE 18

Ex. Column 2 Column 3 Column 4 Data BMS : Br I Br MH = N N 380 ; N-mp=l 75- N N N 1760C HAN N 3 NH2 LCMS : Br Br MH+= LCMS : Br I Br MH = N N 398 ; mp= r 156- F N-N N F N-N 157 Oc Cl han N 4 NH2 LCMS : N LCMS : Br I Br MH = N N 398 ; mp= 45-49oC F N-N N F N-N C ! HN. N N NH2-I-cms- ci ci MH'= 354 ; mu= 43-46-C Ct HN. kN 6. '. NH2, LCMS : N 1 Cl F C C) MH'= CI HAN Ci han \ N CI NH \ LCMS : CI MH+= 354 ; m = 149_P F N o N N 1500C un 0 N NH2 LCMS : Br MH+= 414 ; mu= 86-92oC ICON Han Cl ci han Br MH S : N N 414 ; mp= 185- c I N- HAN I I N CF3 NH2 CF3 LCMS : M H+= Br Br 448 ; mp= 167- N Ci han KIN ci HN 10 Br NH2 Br LCMS : N N MH+= 346 ; mp= \ N I \ N, N 57-58°C I N HN N N 1 1 Br NH2 Br LCMS : N"N MH+= N, Cl dN HN mp=122. N 9-125. 3 HO OC I \ N 12 Br NH2 Br LCMS : N N MH+-- 360 ; mp= 127- 128oC CI N HN N- N 13 NH2 LCMS : N N 342 ; mp= 133- N-N N-N 1350C ci HN N N 14 NH2 Lcms : MH4= N N 344 ; mp= I 52- N N N-N 1550C c ; i HN C) HN kN 15 Br NH2 Br LCMS : N N MH+= 362 ; mp= N-N + N-N 164- Ci O 167°C Han N, 0- I I 16 NH2 LCMS : CN MH+= 327 ; mp= 146- N HN ci HN r' r Y Y YN Y C ! HN. 17 H NH2 H LCMS : mu- mu+= X t 71-820C a HN CI HN y N 17. H NH2 H MS : MH+ 1 c I (t t N 9 \ ; H N) 4 > S .. = 332. \ NN [ N \ NN CI HN N 18 H3C NH2 H3C LCMS : mu = /N /N 346 ; op- 58-65 C \ N, N I N \ NN CI HN y LCMS : 19 \ Br NH2 I Br MH+= 19 NH2 LCMS : I HCI 211- N N 2130C N Ci O HN N 6 O 20 I Br NH2 I LCMS : Br MH+= /N C) HN. 0 HCI 194- Zon F N-N N, 0 F N-N 1970C ci HN /il 21 Cl NH2 ci MS : Br Mu+- /N\ /N\ 414 M. P. 211 Zon Ci han IN N 22 Cl H2N LCMS.. Br Br MH+= i N N O i N 544 ; mp= 104- N-N N-N 1070C ci F3C HN F3C kNO 23 Br H2N HN Yield N N 83% LCMS : OMe N-N 0 e N-MH+ Cl NH N N 410. CL NU N H2N Yield 8 /o N N LCMS : yN-TN N N N 410. ce NH ZON 25 MeO H2N MeO Yield Br Br 96% N YBr Y3 N, l N LCMS : N-N N N-N 440. Ci NH 6 N 26 MeO H2N MeO Yield Br Br 99% MeO . eO N-N N-N 440. Ci NH ZON N H2N Br Yield 27 ber 89% N ci N ci LCMS : mu N N 448. N CI NU N ber Br Yield = 78 lo ci N ci N LCMS : MU a . N a N . ci NH ZON N 30 H. N Y 30 Br H2N Br Yield S Q \ Mu = c 11 ci LCMS : ci N-cl N-MH+ = C Cl 0'N F C ! N 3 0 NH N N 483. f ! P'"1 f ! P'77% ci F F NH I F F 31 NH2 F Yield (35/o ci N LCMS : /1 MH" ci Cul FF 32 H2N Yield 77/o CI N, CI N LCMS : mu = 515. cl ci ci NH ci cl Yield = 33 I N Br H2N/ N Br 100% s s M. P. /179oC N N N LCMS : NH MH+ 388 N I I N 34 Br H2N Br Yield s s M. P. W N, N \ ! \ N, 186°C N N N LCMS : CI NH MH _ CF3 456 N I I CF3 35 Br H2N Br Yield N N 98% s N s M. P. /181 oC W NN N N N LCMS : CI NH MH+ = CH3 401 N ZON 36 Br H2N Br Yield = r- 1 rY' N\ (N\ (63% M. P. NH LCMS : CI MH+ _ S02NH2, 480 02nu2 37 Br H2N Br Yield = N N 75% m. p. 126 N, N N I N-N NH LCMS : CI MH+= ci N 400 mu+ = 400 38 Br H2N Br Yield = </>"N vt), <z>"N > 94 % N m. p. 132 m. p. 132 N_N \ N1N-133°C LCMS : A M4Ho+o= razz N N 39 Br H2N Br Yield = . Nr N 95% , r, m. p. 121 N-Nz LCMS : MH = 400 N 40 Br H2N Br Yield = N N 98% Me LCMS : NN I w N_N Ni 460 cl OMe I LOCHS 41 Cl Br H-2N Cl Br Yield = N N 87% [bN 464 N m. p. 170 1 464 LCMS : CI NH MI-i+= 464 N I 42 C g,-HzN CI B Yield = 84% m. p. 216 cl Cl dNH MF = _cul CI MH''- ! 464 if N 43 Br H2N Br Yield = 1 rYY Cl nu 96% LCMS : NU 2140C W N 44 Cl Br H2N Cl Br Yield = N bN 95% ome M. P. N I 1580C N LEMS : CI NH MH+= uMe H3CO 522 OCH3 45 C02Et H2N C02Et Yield=90 N (% LCMS : N-N'N-N/MH+= C) N MH ci N NH 278 N N 46 I W Br NH2 Br YieOldQ 10 N N LCMS : LCMS : T C) NH NJ N-N N N-N MH+=394 N IV N'N NH NU 47 H2N LCMS : /N N p/N 473 m. p. 84- \ N N O \ N, N 87°C ci HN"'ON 0 N¢O 0f 48 NH2 MS : Br Br MH- N N 396 m. p. 91. 5 CI HAN /ici ci han 49 NH2 MS : Br Br + N 396 N-N-m. p. 196 zon C p-HN N+ 50 Cl NH2 ci MS : Br Mu* _ N N 430 \ N N. _ m. p. 242 Cl O-HNA O- ci HN Nez ci Cl Br ci NH2 I Br C Cl 430 m. p. CI NN N ; _ CI NN 218°C O C) HN. \ N ; _ 51 NH2 MS : e Br l z I Br MH+= N, o- 52 Cl, Br NH2 Cl Br MMHS+ : = N N 430 N N M. P. 230 oN-N N 2330C Cl O-HN + 6- O- Br Br MH+ N N 405 /N\ (/N\ (405 zon W N N I N N N-188°C Han N I I N MH+ 55 gr NH2 B MS : 370 N-N N-N m. p. 229 \ NN N N N-232°C CI HAN ZON I I N 56/I Br NH2/I Br MH+'- O 370 ) N-m. p. 85- N N N N 900C zon 90°C HN N N 57 Br NH2 Br MS : O O 386 N. _-230°C Han N ; _ 0 HN. 6 58 Br NH2 Br MS : F3C"N *rA 10 F3CN 4 M3H7+2= ton 3 % N-N g 1 gNsN m. p. 212 Cl vN HN-215°C /ICI N 59 Br NH2 Br H3C 4 HC NJ MH = T 318 _N m. p. 169 Cl wN HN-171°C HAN N I I 60 Br NH2 Br MS : _--N MH+ _ 332 N) N m. p. 170 Cl wN HN-173°C N kan 61 Br NH2 Br MS : N MH+ _ 346 \ N Ci HN. N CI HN II 62 N Br NH2 Br MS : N MH* _ 360 N m. p. 114 T N ;-116°C HAN KAN 63BrNH2BrMS : N\ MH+= 348 N'N + NN m. p. 197 Cl wN HN-116°C un N, o- I I Cl mp= Br 230-232 N N 2. M+H = 396 > R N-N HN un ICI I ho NUS 65 gr H2N I Br 1. mp = N N 205-207 -2 HCI N N 2.NM+H 402 ci HN KAN NHs il N NH2 66 1. mp = Br 220-223 I N (2. M+H = -2 HCI N NF 414 F N-N F N-N 0 HAN. TON NU2 NH2 67 Br H2N 191-193 N N c 11 N-N ci N-N 431 2. HN N Nu2 1. mp N NHZ 1, mp = gg Br HCI H2N/Br 235-237 o 235-237 397 NN N N N'N ZON NON NON NH2 69 r R. HO-HsN. r , 69 Br 1. mp = N >250 N-2. MH 2. M H = " NU2 N-,, N nus NH2 N Y N NH2 70 Br HGI H2N/ 1. mu = N 230-232 I 2. M+H = F F C' HN nu2 NON NH2 I NH 71 Br 2HCI H2N Br 1. MP 1. mp = N N 235-238 Zon CI \ NN N N CI NN 431 NH2 Non NON Non NH2 72 Br H2N Br 1. mp X f NH2 f { N HCI N N N 186-188 N-H N-2. M+H 2. MHz N N 410 Cl HN N 1. NH NH 73 i Bu 1. m 136-138 r2 HT -2 HCI 2. M+H N-N 0 han. IN ZON NAZI 74 Br H2N B r N-2 HCI N 1. mp 192-195 N-2. MH Cl N N-N 450 N HN B N ton N N N 2 HCI N Br 1. mp = 88-90 N-2. M+H N N N-N 454 HN HN ORME zon NH OMe tN 76 Br H2N Br 1. mp N HCI N 230-232 230-232 N 2. M+H zon CI HN HN ci HN HN ZON f nu y J 77 Br H2N Br 1. mp = 77 < Br H2N lnl Br 1. mp = N. 3 HCI N 131-133 \ N 2. M+H= N/\ N N 479 ci (N) HN N N (N) N Br 2 \ Br 1. mp- O N 85-88 2. M-N = N'N 376 ci HN 0 O N /1. mp = O I gr 131-133 79 n Br H2N ~< 1. mp F N-N 388 zon ce F \ non HN 80 Br H2N Br 1. mp 1. mu = - 2 HCI N N 206-208 N-NH2 N-2. M+H N N 408 Ci han ZON SUA NH2 nu 1. m 81 N/Br 2 HCI N Br 108-1 0 i 2. M+H = N N NHBoc 502 N NHBOC Ci han N NHBoc 82 Br H2N I N Br 1. mp = N N 83-85 N-N. 2 Hcl N-2. M+H N 402 CI'HO N nus N NH2 83 zizi Br H2N nif N Br 1. mu W N I N \ N 220 F F N N 414 Ci han N NH2 N 84 Br H2N--"-Br 1. mp = , N4 2 HCI H g, N4 254M1+5H6 = N N N 154-156 oye NN 426 HN N HN 85 Br H2N'Br 1. mp N 152-153 Tr HCI H 2. M+H Pu Ci han HO HN 86 Br 2N'Br 1. mp N N N 159-161 <, HCI H 2. M+H N-N N-N 420 HN N HO 87 n Br H2N<NS ln Br 1. mp = N N N >220 cl HCI HCI H ci N-2. M+H I Cl y han N N 455 HN 88 g H2N I j Br 1. mp = N 223-225 2. MHz N-N N-N 425 C ! HN. HN 89 H Br 1. MP 1. mp = N Br 2N 199-201 2. MHz N N 419 Ci han HN 90 Br H2N Br 1. mp = N) N'N 184-186 2. M+H = N-N N-N 426 C ! HN. HN-N han-N 91 I Br H2N I I Br 1. m N Br 2N N'N 196-198 2. M+H = N 420 CI HIV HN-N HN-N 92 Br H2N Br 1. mp N-2 HCI N 156-159 2. M+H N N 440 ci HN HN N HN Br p = N-2 HCI N 173-176 2. MH ZON N-N N N-N 434 H-V N HN 94 I g,-H2N Br 1. mp = 2 HCI/ I N 173-175 2. M+H Pu GI HN HN N HN 95 Br H2N Br 1. mp N-2 HCI N 174-176 2. MH ci N-N N ci N-N 469 aN Cl N N _ HNA 96 H N C 1. mu N N_N 2 Hci 2. M+H \ Nz Ci ho N NU nez / g7 Br HaN N N 441 H nu i 2. M+H = N'N 441 Cl HN HN 0 HN- HAN HAN 98 Br H2N/ bd 1. mp = 98 N 202-205 Zon N'N 434 CI HN. ( HN HO HAN HO 0 Ho i Br 1. mp- N N 209-212 2. M+H = N N 453 CI HN HN 0 HN- H N 100 Br H2N Br 1. mp 1. mp = N N 219-221 PyN-p N N 469 X Ci HN HN 0 H NU han han O 101 N Br H2N N Br 1. MP 1. mp = N 64-66 2. MH N-N N-N 403 OH HUI In OH 102 i--i 1. mu = N N 168-170 Ct HN. HNN N-H2Nj-, N-2. M+H N-2 HCI H N 420 ce HN HN N 103 Br H N 213-216 2. MHz NH NON Nu cl HN 104 BzCN gr HZN N CbzN Br _ mp = N I/ N 98-100 . zu HCI \ NN N'N 2. M+H = HN 561 HO N HN 105 BzCN Br H2N CbzN Br 1. mp N-3 HCI N 70-72 1 2. M+H N N N 608 HN H N N . NH 106 Br HCI HN Br 1. mp CBZN N CbzN 168-170 2. MH t+N-N N N N-N 538 HN ci NH2 N N NYN I NH2 1D7 HN 107 Br H2N Br 1 mp CBZN N-2 HCI CbzN N 189-191 2. M+H = N N N 592 Ci N HN zu ZON N | 108, < Wr [ 108 Br H2N Br LCMS : Mu = zon j 458 ; Br N-N IN Br-N 458 ; Ci HN v oc ci han Yield = 109 NH2 Yield BMS : Mu+ _ mu+ CI NH 131-132 oC 110 F H2N F Yield=95% Br N \ > Br N \ LCMS : Mu+=347 NN/N N/ HAN I I Et02C F Yield=91 % Br N H2N Br N 3H) ; LCMS : N, N//I N, N i MH+= 484 Ci Et02C NH Et02C 112 Yield=87% Br N H2N Br N LCMS : MH+= 427 N-N N-N ci N H 113 Yield=80% F/F/ Br N H2N Br N LCMS : MH+= 427 N CI \ H NH ci H t4H 114 Br 0 H2N Br 0 Yield=91 % OEt/\ 'N OEt LCMS : MH+= 378 N-N N N_Nt MH+= 378 HN N 115 Br H2N Br Yield=92% , O/ Br N \ I N-Br N LCMS : w w v w MH+=520 N, N/O N, N/O Han Cl HN N 116 Br NH2 Br Yield=98% O//LCMS : 1-10 Br LCMS : w w \ N_ CI HAN o- 'o Cl han 117 N N LCMS : MH+=41 0 - N/ CI H N \ N-i-O Cl Ns 118 H2N Yield=95% Br Br LCMS : N MH += 347 M H+= 347 N, N/N, N i N_Nt N-NHt I j CHZNHZ Yield = F N 65% Br N \ F LCMS : \ 'NN Y MH+= N-N N HN 481. 02 ci NS t 6 -.'S N-S 126 CH2NH2 Br Yield=71 % 0 tN Xs 1 4 W Br MHs = 4660 N-NCl HNaN bu F-yN_ C ! j HAN SUS cl N S 127 CHZNHZ Yield=71 % F/I/Br [VH+ _ ZON Br F N-495. 1 Cl w N-N CRI CI/ N 128 cH2NH2 Yield=ss% i I i N (MH+ = 463 F N-N N HN \Cbz cri N N 129 F CH2NHz. HCI Yield = i< i f) Cl N $ Br N N Br 77% N LCMS : N, N \ NN MH+= ci COOMe HN 455 1 CORME COOMe 130 CH2NH2. HCI--7H N-MR VqzN<lU o>OMe 9"N\Ct (Yield = Br N 0--l-OMe N Br (Yield Tir F 75% NN/ LCMS : CI HN MH+= 379 O ORME 131 F/CIH. H2NH2CE Yield = N N 0 N 75% LCMS : Lems : Mu+= 407 CI HN ^ _pEt 0 132 0 Yield F N 2NH2C 75% i LCMS : N-N N MH+ = 421 o MH+= 421 Ci HN out 133 CIH. H2N ot Yield HN OMe N W W "I Br LCMS : Nz 134 S =421 CRI ci N-N Il 0 134 F CH2NH2. HCI Br Yield Br N 78% Lems : I LCMS : \ fuzz NEZ N, N N MH = 475 S02CH3 HN CI S02CHg 135 CH2NH2. HCI Br Yield N \ I I/j, Br 75% I F LCMS : Br N N 75% CI S02NH2 HN 476 LEMS : QU 136 H N Yield = Cl Wo Lems : NN + N, N i o MH ° pJ HN 455 ci 0 I-) 137 F H2N Yield = r LCMS : N, N F \ NN MH+= 473 Ci han ruz O 138 F HZN Yield = F Br \ N\ w I I/N LCMS : I fuzz N-N N F N N MH+ 439 C !"han ZON N-0 139 Yield Br N \ I I/N/Br 65% BMS : LCMS : 441 Ci H2N HN 441 (/ 0 140 H2N Yield Bu I/N B 80% i BMS : C !"han N C ! I . N cl 141 F HNN er Yield = N 60% Nz F Cl N mu =330 /NiN i i \ i. i i i mp=109- N-N N N-N illoc Ci HN ZON N 143 NH2 LCMS : M MH+=346 N mp=186- i (I i mp=186- N N, 0 N-N 1880C Ut han CI HN Nz " " mu=148- /NiN a HN. ci han CI HN /il 145 CF3 NH2 CF3 LCMS : MH =400 Mu=186- w N, W N, mP= 086- N-N Nso N-N 1 88°C HN ru 0 Br Br M2H+=39 M2 H+=39 mu=192- l mp=192- N-N N N-N 1940C Ci han N N 147 o NH2 0 LCMS : M+=404 ; N mp=220- C f ! i', 222°C Ut han a HN. 0 I I 148 NH2 LCMS : MH+=369 I/N I/N, ; mp>2300 N-N N-N c ci HN2/HNn N NN 149 NH2 LCMS : MH =364 zon i i i' Mu=186- a HN. HN /il \ N, N N MH+=312 NH2 MH+=312 N-N N-N mp=138- ci N, 0 HN 1400C CI HAN N, 0 W NO 151 I NH2 I LCMS : M =380 ; Cl N mp=172- 174 C ci ! I N 1 !/> 174°C O Han I HN N, 0 NO 152 LCMS : Mu+=352 N N N, Ct HN. 0 Ul HN W Nz LCMS : 153 OCH3 2 OCH3 MH +=348 /N \ (\/N ,. ( mu=166- N-N N, o N 168"C N ci HN /,I W Nz BMS : N N 1 ; -tu /N \/N 1 ; mp o 8_ N-N N-N 80 Oc Cl O"SsNH HN) O NH (H3C) 2N (0), oSuNH NZ NH LCMS : Br Br M2H+=47 N N 4 ; mu=161- N N 1630C C ! O HN O HN / o*r ONH 156 NH2 LCMS : Zon (\ N m=p=48- 1 ' f) t ! 1' 51°C Me0 O \ NN N Me0 O NN CI HAN N \2N r ! P 4 ? 1 zon ci N-N cl N-N ci H N NHBOC NHBOC /NH2/MH+ _ 158 \ I N Br \ N Br 520. 1 NBOC t 158"NoA T, Ne M52HO+. 1- Ci YN-N Cl YN_N N CI HN NBOC 159 Br H2N Br N N 542. 1 Cl Cl I Cl N-N ci N-N C'NHBOC HN NHBOC /NH2 MH+ _ I I N 480. 1 NHBOC ci Ne, 0 cl N-N Cl HN NBOC 1 161 \ I N Br \ I N Br 506. 1 i i N i i BOUC CI T CI \ NN Cl HN xoc BOC 162 \ I N Br \ I N Br 480. 1 NHBOC ci N-N NHBOC cl N-N Ci han N NHBOC BOC 163 \ I N Br \ I N Br 494. 1 CI \ N CI N NHBOC C HN NHBOC NHBOC 'Mr''r'E'rBr' NHBOC CI NN CI NN Y N NHBOC Y N C ! HN. NHBOC ci N- cl cul NHBoc HN NHBOC C) HN. NHBOC 165 -_-. Br HN MH* _ Ber 494. 1 r i ci N-N IINHBOC N-N C N'N NHBOC _y C I 166 -NH2, MH+ _ Ber 508. 1 N N y NHBO HN Cl HN NBOC 167 Br H2N Br M H 520. 1 Pin C YN_N NBOC Cl YN_N CI HAN 1 NHBOC 168 i MH _ N N 528. 1 Cl \ NN /CI \ fVN NHBOC CINHN NHBOC NHBOC 169 N_N NHBOC HN N N 520. 1 N Cl Cl BOC H N BOC /H2N/MH' _ 170 Br 2N Br MH N 528. 1 N NHBOC HN NHBOC 171 Br H2N Br LCMS : Mu+= Nz Ci HN 0- -N CI HN /1 I HAN \ nez 172 ci H2N Ci LCMS : CI CI MH*= N bon N-N N-N w N N W N N ci HN zozo 0 173 Br H2N Br LCMS : MH = F N N H W N F F N'N/F N'N N Cl W HN N02 nu N NOs I N02 F 174 Br H2N Br MH+ _ zon F 1 ON = N 0 H N CI N'O HN Me Zozo I I Me 175 B r H2N F LCMS : Cl YeN e N MH 2 own 426. 2 76 1 WANEo N q ME HAN Me , Me Mye Me mye 176/Br H2N F LCMS : Br N Me N MH+ = / 42, 0 ZON NON , mye Me Nô Me 177 Br NH2 F Br LCMS : Bu N r MH+ _ N mu 1 N N NN CI HN N. Me 178 H2N Yield = 90 Br/ Br MH" N =436 N m. pt. _ N 89. 1 °C CRI NU ICI N 179 1-0 H2N f-0 0 0 =424 Br Br M. pt. N 188. 2 OC N ION KAN ci nu I N 180 cl H2N cl Br Br =448 N N M. pt. 211. 3 °C Cl j, N_N wN NH Cl Cl N NI W N 181 cl H2N ci Yield Br Br quant. N N MH+ I + 464 Cl cul CI NU Nu W nô 182 N H2N N s8 N4, \N N m. pt. _ N fA"N\< 382 N-N N 185. 8 °C nu kan N N , ! yN ! yin 387 N-N N-N M. pt. 181-182 CI NH °C Nu oc N \N7 XNY MH= \ (MH = 453 N-N IN N-N CI CF NH 3 / N N CF3 1 5 gr H2N , ! yN W N, N \ N S - m. pt. _ , nu NH CHUS zon CH3 186 Br H2N Br + S N \ S N /\ 402 W N, /I I + W N, N N MH y nu /il+ W Nô 0- Br Br 91 Mu+ _ 386 N-N N N-N M. pt. Ct NH 148. 3 °C ZON N Br Br 65 / I + _ N 402 w N, N w N. W N, N m. pt. _ 174. 5 °C \ IN°O 189 Br NH2 Br °C N N 379 own- Own 0 M. pt. N-N N-N Z : 82-83 Nu cl 0 190 B NH2 Br Mu+ _ 379 L S. CHNH CI NU 'O 191 NH2 Yield N N $9 MH+ x 469 W NN N'N m. pt. _ I NH 186. 70C N » N N S-N 192 NH2 Yield SN b i i/r i MH+ _ 410 w NN W NN m. pt. _ ci CN NH 86. 70C CON 193 _ NH2--___ Br Yield = Cl mu+ 333 w N, N w N, N m, pt. _ Cl NH 1 20. 3°C I C ! NH 120. 3°C 194 NH2 Yield Br N Br 86 Mu+= Ho 353 195 Br ro H2N > Br rO Yield=11% N-N N-N M. pt. 9\N _N e @ N X N_N t MH+= 390 CI NH HO 195 Br 0 H2N Br N 0 Yield=l 1 % BMS : 374 , N/MH+= 390 IN CI /\ HN + + 196 Br O HN Br Yield=88% N LCMS : 374 N-N N-N MH+= 346 NN/ N Cl HNa han NU 197 Br 0 H2N Br 0 Yield=88% N LCMS : 374 MH+= 346 N N HAN NJ 198 NH2 Yield = N N ( H+ _ 400 M. pt. N-N N N-N 111. 5- CI NH 112. 2 °C N N 199"-'2 ! ! f f] Br MH"= 199 Br NH2 Br X < > Zon fizz 0 NU N, oxo 200 Br NH2 Br N N MH+ _ i r/i 415 I 201 N N N-N CI NU /I N-, N 201 Br NH2 Br 201 Br NH2 Br mu+ N, N II N, N m. p. _ 156. 5oC Ct. NH kan I I N 202 Br NH2 Br Mu+= /N 414 \ N, N \ NO N, N m. p. = Nz Nu N, oC- 0 203 Br NH2 Br MH+= LJ N N N-N ci T AN H Nz CI NU Non ber 86 Ber 86 CLIN \ N, /N 521 W N, N m. p. _ CL 79. 9 OC NON N I I B 204 B NH2 . 10 Cbz'N N Cbz'N N N \ NN I ZON NI NU N . ah kan . 11 N N 87 'N-N)-/ I'N \ N Cbz \ NN Cbz N I NH 128. 6 °C C I I N 205 Cbz, N Br NH2 Cbz, N Yield = N Br Br 99 N MH+ N-537 N N N, N- H 83. 5 °C /ici+ neo 206 Cbz, N Br NH2 Cbz, N Yield = Br 94 N N MH+ w N, N I > 598 \ NN m. p. = S02CH3 NH 110. 8 OC 02cl3 \ S02CH3 207 Cbz s N NHz Cbz s N Yield- Br quant. 545 'N CN NH 'CN. NH CN 208 Cbz, N Br NH2 Cbz, N Yield Br 96 Mu+ _ N-N 468 N M. P. i IRNH 69. 2 OC 209 Cbz. NH2 Cbz Br MH = N ( T, N 498 /N, N I N 226. 5 OC CI S02NH2 NH S02NH2 210 Cbz, N Br NH2 Cbz, N Br MH+ = Bu , N 564 W NN -N 174. 2 OC cl C02H NH COsH

Additional data for select examples given below.

Example 23: 1H NMR (CD30D) 8 8.63 (d, J = 5.7 Hz, 2H), 8.18 (s, 1H), 7.81 (dd, J = 8.1 Hz, 2.1 Hz, 1H), 7.58 (d, J = 6.0 Hz, 2H), 7.48 (m, 1H), 7.15-7. 10 (m, 2H), 6.50 (s, 1 H), 4.86 (s, 2H), 3.70 (s, 3H) Example 24 : 1H NMR (CDCI3) 8 8.82 (s, 1 H), 8.73 (d, J = 4.2 Hz, 1 H), 8.11 (s, 1H), 8. 06 (dd, J = 7. 8 Hz, 1. 8 Hz, 1H), 7.91 (d, J = 8. 1 Hz, 1H), 7.53-7. 47 (m, 2H), 7.20 (m, 1 H), 7. 08 (d, J = 8. 1 Hz, 1 H), 6.75 (s, 1 H), 4. 81 (d, J = 4.5 Hz, 2H), 3.86 (s, 3H) Example 25: 1H NMR (CDCl3) # 8.75 (d, J = 5.7 Hz, 2H), 8.12 (s, 1H), 7.81 (d, J = 2.1 Hz, 1H), 7.53 (dd, J = 8. 4,2. 1 Hz, 1H), 7.45 (d, J = 6. 0 Hz, 2H), 6.96 (t, J = 6.0 Hz, 2H), 6.33 (s, 1H), 4.85 (d, J = 6.0 Hz, 2H), 4.09 (s, 3H), 4.03 (s, 3H) Example 26 :'H NMR (CDC13) 8 8. 82 (s, 1 H), 8.72 (s, 1 H), 8.09 (m, 1 H), 7.87- 7.83 (m, 2H), 7.60 (m, 1 H), 7.45 (m, 1 H), 7.03 (d, J = 8.4 Hz, 1 H), 6.87 (s, 1 H), 6.43 (s, 1 H), 4.83 (d, J = 4. 5 Hz, 2H), 4.11 (s, 3H), 4.04 (s, 3H) Example 27 : 1H NMR (CDCl3) 8 8.75 (d, J = 4.5 Hz, 2H), 8.19 (s, 1H), 7.63 (d, J = 7.8 Hz, 2H), 7.44-7. 40 (m, 3H), 7.07 (m, 1H), 6.26 (s, 1H), 4.83 (d, J = 5. 1 Hz, 2H)

Example 28 : 1H NMR (CDC13) 8 8.86 (s, 1H), 8.74 (m, 1H), 8.17 (s, 1H), 7.97 (m, 1H), 7.66-7. 63 (m, 2H), 7.62 (m, 1 H), 7.41 (m, 1 H), 7.07 (m, 1 H), 6.35 (s, 1H), 4.87 (d, J = 6.0 Hz, 2H) Example 30 : 1H NMR (CDC13) # 8.16 (s, 1H), 7.66-7. 62 (m, 2H), 7.41 (m, 1H), 7.33-7. 22 (m, 3H), 6.96 (t, J = 6.0 Hz, 1 H), 6.33 (s, 1 H), 4.73 (d, J = 6.0 Hz, 2H) Example 31: 1H NMR (CDCl3) # 8.13 (s, 1H), 7.66 (d, J = 7.8 Hz, 2H), 7.45-7. 40 (m, 2H), 7.10-7. 04 (m, 2H), 6.93 (t, J = 6.6 Hz, 1H), 6.60 (s, 1H), 4.84 (d, J = 6. 6 Hz, 2H) Example 32 : 1H NMR (CDCl3) # 8.16 (s, 1H), 7.66-7. 62 (m, 2H), 7.57-7. 55 (m, 2H), 7.41 (t, J = 7.8 Hz, 1 H), 7.31 (dd, J = 7. 8, 1.8 Hz, 1 H), 6.99 (t, J = 6.0 Hz, 1 H), 6.32 (s, 1 H), 4.73 (d, J = 6.0 Hz, 2H) Example 40 : 1H NMR (CDCl3) # 8.01 (s, 1 H), 7.31-7. 24 (d, J = 8.2 Hz, 1 H), 6.72-6. 64 (br t, J = 5.4 Hz, 1 H), 6.62-6. 52 (m, 2H), 6.05-6. 01 (s, 1 H), 5.56- 4.64 (d, J = 6.0 Hz, 2H), 4.03-3. 93 (s, 3H), 3. 94-3. 86 (s, 3H), 2.79-2. 70 (d, J = 8.1 Hz, 2H), 2.02-1. 66 (m, 6H), 1.43-1. 22 (m, 3H), 1.20-1. 02 (m, 2H) Example 45 : 1H NMR (CDCl3) # 8. 73 (d, 2H), 8.54 (s, 1H), 7.41 (d, 2H), 7.02 (br, 1H), 5.90 (s, 1H), 4.80 (s, 2H), 4. 48 (q, 2H), 2.75 (s, 2H), 1.50 (t, 2H), 1.06 (s, 9H); Example 46: 1H NMR (CDCl3) # 8.79 (s, 1H), 8. 72 (d, 1H), 8.14 (s, 1H), 7.84 (d, 1H), 7.54-7. 33 (m, 4H), 6.97 (t, 1H), 6.18 (s, 1H), 4.79 (d, 2H), 2.47 (s, 3H) Example 108: 1H NMR (CDC13) 8 8.79 (s, 1H), 8. 72 (d, J = 3.0 Hz, 1H), 8.16 (s, 1 H), 7.84 (d, J = 7.8 Hz, 1 H), 7.74 (d, J = 7.5 Hz, 2H), 7.55-7. 35 (m, 3H), 6.92 (t, J = 6.3 Hz, 1H), 6.42 (s, 1H), 4.81 (d, J = 6. 3 Hz, 2H) Example 110: 1H NMR (CDCl3) 8 8. 18 (t, 1H), 8.03 (s, 1H), 7.44 (m, 1H), 7.30 (t, 1H), 7.17 (q, 1H), 6.66 (s, 1H), 6.56 (br, 1H), 4.28 (d, 2H), 2.38 (s, 1H) Example 111 : 1H NMR (CDC13) # 8.72 (br, 1H), 8.59 (d, 1H), 8.11 (t, 1H), 8. 06 (s, 1H), 7.73 (d, 1H), 7.44 (d, 1H), 7.42-7. 21 (m, 3H), 7.07 (q, 1H), 6.39 (d, 1H), 5.21 (q, 1H), 4.16 (q, 2H), 3.08 (d, 2H), 1.22 (t, 3H) Example 112 :'H NMR (CDC13) 8 8.22 (t, 1H), 8.15 (s, 1H), 7.51-7. 33 (m, 7H), 7.21 (q, 1H), 6.82 (d, 1H), 6.51 (s, 1H), 4.68 (q, 1H), 2.18 (m, 2H), 1. 17 (t, 3H) Example 113 : 1H NMR (CDCl3) # 8.22 (t, 1H), 8.14 (s, 1H), 7.51-7. 33 (m, 7H), 7.21 (q, 1H), 6.82 (d, 1H), 6.51 (s, 1H), 4.68 (q, 1H), 2.18 (m, 2H), 1. 17 (t, 3H)

Example 114 :'H NMR (CDCI3) # 8. 81 (s, 1H), 8.75 (d, 1H), 8.21 (s, 1H), 7.84 (d, 1H), 7.47 (q, 1H), 6.96 (s, 1H), 6.94 (t, 1H), 4.85 (d, 2H), 4.60 (q, 2H), 1.58 (t, 3H) Example 115: 1H NMR (CDC 8 8.77 (s, 1H), 8.72 (d, 1H), 8.14 (s, 1H), 7.83 (d, 1H), 7.65 (d, 1H), 7.44 (q, 1H), 7.80 (t, 1H), 7.6 (d, 1H), 6.18 (s, 1H), 4.75 (d, 2H), 3.91 (s, 3H), 3.81 (s, 3H) Example 116 : 1H NMR (CDCI3) 8 8. 67 (s, 1H), 8.55 (d, 1H), 8.50 (s, 1H), 7.92 (d, 1H), 7.90 (d, 1H), 7.78 (t, 1H), 7. 10 (d, 1H), 6.97 (s, 1H), 5.11 (s, 2H), 3.77 (s, 6H) Example 117: 1H NMR (CDCl3) 8 8.38 (s, 1H), 8. 30 (d, 1H), 8.17 (s, 1H), 7.52- 7.37 (m, 6H), 6.97 (t, 1H), 6.13 (s, 1H), 4.77 (d, 2H), 2.50 (s, 3H) Example 118 : 1H NMR (CDCl3) # 8. 18 (t, 1H), 8.03 (s, 1H), 7.44 (m, 1H), 7.30 (t, 1H), 7.17 (q, 1H), 6.66 (s, 1H), 6.56 (br, 1H), 4.28 (d, 2H), 2.38 (s, 1H) ; Example 121 : 1H NMR (CDCl3) # 8.6 (S, 1H), 8.15 (dt, 1H), 8.1 (s, 1H), 8.0 (d, 2H), 7.5 (d, 2H), 7.4 (dd, 1H), 7.2 (d, 1H), 7.15 (dd, 1H), 6.8 (t, 1H), 6.6 (s, 1H), 4.75 (d, 2H).

Example 126 :_ 1H NMR (CDCl3) # 8. 15 (dt, 1 H), 8.0 (s, 1H), 7.5 (d, 1H), 7.42- 7.35 (m, 2H), 7.3-7. 2 (m, 2H), 7.15 (dd, 1 H), 7.1 (dd, 1 H), 7.0 (t, 1 H), 6.6 (s, 1H), 4.8 (d, 2H).

Example 127: 1H NMR (CDCl3) # 8.2 (dt, 1 H), 8.0 (s, 1 H), 7.4 (dd, 1 H), 7. 3- 7. 25 (m, 3H), 7.1 (dd, 1 H), 6.9-6. 85 (m, 2H), 6.7 (t, 1 H), 6.6 (s, 1 H), 4.6 (d, 2H), 3.2 (m, 4H), 2.6 (m, 4H), 2.3 (s, 3H) Example 128 : 1H NMR (CDCl3) # 8.15 (dt, 1H), 8.1 (s, 1H), 8.0 (d, 2H), 7.5 (d, 2H), 7.4 (m, 2H), 7.25 (d, 1H), 7.2 (s, 1H), 7.15 (dd, 1H), 7.0 (s, 1H), 6.8 (t, 1H), 6.6 (s, 1 H), 4.75 (d, 2H).

Example 129 : 1H NMR (CDCl3) # 8.15 (dt, 1H), 8.05 (s, 1H), 8.0 (d, 2H), 7.5 (d, 2H), 7.4 (m, 1H), 7.3 (dd, 1H), 7.15 (dd, 1H), 6.9 (t, 1H), 6.5 (s, 1H), 4.75 (d, 2H), 3.85 (s, 3H) Example 130: 1H NMR (CDCl3) 8 8.2 (dt, 1H), 8.0 (s, 1H), 7.4 (dd, 1H), 7.3 (dd, 1H), 7.15 (dd, 1H), 6.8 (t, 1H), 6.4 (s, 1H), 4.2 (d, 2H), 3.8 (s, 3H).

Example 131 : 1H NMR (CDC13) 8 8.2 (dt, 1H), 8. 0 (s, 1 H), 7.4-7. 15 (m, 3H), 6.7 (t, 1 H), 4.2 (q, 2H), 3.8 (dt, 2H), 2.8 (t, 2H), 1.2 (t, 3H)

Example 132 : 1H NMR (CDCl3) # 8.2 (dt, 1 H), 8.0 (s, 1 H), 7.4-7. 15 (m, 3H), 6.7 (t, 1H), 4.2 (q, 2H), 3.8 (dt, 2H), 2.8 (t, 2H), 2.05 (m, 2H) 1.2 (t, 3H) Example 133 : 1H NMR (CDCl3) # 8.15 (dt, 1H), 8.0 (s, 1H), 7.4 (m, 1 H), 7.3 (dd 1H), 7.2 (dd, 1H), 6.5 (s, 1H), 6.4 (t, 1H), 3.7 (s, 3H), 3.5 (dd, 2H), 2.4 (t, 2H), 1.8 (m, 4H) Example 134 : 1H NMR (CDCI3) # 8.15 (dt, 1H), 8.0 (s, 1H), 7.95 (d, 2H), 7.6 (d, 2H), 7.4 (m, 1H), 7.25 (dd, 1H), 7.1 (dd, 1H), 6.9 (t, 1H), 6.5 (s, 1H), 4. 8 (d, 2H), 3.0 (s, 3H) Example 135 : 1H NMR (DMSO d6) # 9.1 (bs, 2H), 8.4 (s, 1H), 8.0 (t, 1H), 7.85 (d, 2H), 7.7 (d, 2H), 7.6 (m, 1H), 7.4 (m, 2H), 6.6 (s, 1H), 4.8 (bs, 2H) Example 136: 1H NMR (CDCl3) # 8. 2 (dt, 1H), 8.0 (s, 1H), 7.4 (m, 1H), 7.25 (dd, 1H), 7.15 (dd, 1H), 6.9 (m, 3H), 6.7 (t, 1H), 6.5 (s, 1H), 4.5 (d, 2H), 4.2 (s, 4H) Example 137 : 1H NMR (CDCI3) 8 8.2 (dt, 1 H), 8.0 (s, 1 H), 7.4 (m, 1 H), 7.3 (dd, 1 H), 7.2 (dd, 1H), 6.9 (dd, 1 H), 6.8 (t, 1 H), 6.7 (m, 1 H), 6.6 (s, 1 H), 5.3 (s, 2H), 4.85 (s, 2H), 4.6 (d, 2H).

Example 138 : 1H NMR (CDCI3) # 8.2 (dt, 1H), 8.0 (s, 1H), 7.9 (d, 1H), 7.8 (d, 1H), 7.4 (m, 2H), 7.3 (dd, 1H), 7.1 (dd, 1H), 6.9 (t, 1H), 6.6 (s, 1H), 4.8 (d, 2H) Example 139: 1H NMR (CDCl3) # 8.2 (dt, 1 H), 8.0 (s, 1 H), 7.4 (m, 1 H), 7.3 (m, 2H), 7.2 (dd, 1 H), 7.1 (dd, 1 H), 6. 8 (d, 1 H), 6.7 (t, 1 H), 6.6 (s, 1 H), 4.6 (m, 4H), 3.2 (t, 2H) Example 140: 1H NMR (CDCl3) # 8.45 (s, 1H), 8.2 (dt, 1H), 8.0 (s, 1H), 7.7 (dd, 1H), 7.4-7. 3 (m, 3H), 7.15 (dd, 1H), 6.8 (t, 1H), 6.6 (s, 1H), 4.7 (d, 2H) Example 141: H NMR (CDCl3) # 8.2 (dt, 1H), 8. 0 (s, 1H), 7.45-7. 1 (m, 7H), 6.6 (s, 1 H), 4.4 (dt, 2H), 2.6 (t, 2H), 1.8 (m, 2H), 1.4 (m, 2H) Example 171 : 1H NMR (CD30D) # 8.41 (s, 1H), 8.25 (d, J = 6.3 Hz, 1H), 8.15 (s, 1H), 7.67 (d, J = 7.8 Hz, 2H), 7.55-7. 48 (m, 2H), 7.45 (dd, J = 7. 5,1. 2 Hz, 1H), 7.34 (dd, J = 7.5, 1.8 Hz, 1 H), 6.28 (s, 1 H), 4.79 (s, 2H).

Example 172: 1H NMR (CDCl3) # 8.64 (s, 1 H), 7.68-7. 64 (m, 2H), 7.52 (m, 1 H), 7.43 (t, J = 7.8 Hz, 1 H), 6.89 (t, J = 6.0 Hz, 1 H), 6.51 (s, 1 H), 6.48 (m, 2H), 4.74 (d, J = 6.0 Hz, 2H).

Example 173 : 1H NMR (DMSO-d6) # 8.86 (s, 1H), 8.46 (s, 1H), 8.32-8. 28 (m, 2H), 7.97 (m, 1 H), 7.87 (m, 1 H), 7.52 (m, 1 H), 7.35-7. 24 (m, 2H), 6.57 (s, 1 H), 6.46 (m, 1H), 3.65 (m, 4H).

Example 174: 1H NMR (CDCl3) d 8.37 (s, 1H), 8.16 (t, J = 7. 5 Hz, 1H), 7.45-7. 35 (m, 1H), 7.32-7. 20 (m, 3H), 7.17-7. 07 (m, 1H), 6.92 (t, J = 6 Hz, 1H), 6.48 (s, 1H), 4.65 (d, 2H), 2.50 (s, 3H).

Example 175 : 1 H NMR (CDC13) d 8.16 (t, J = 9 Hz, 1H), 8.00 (s, 1H), 7.49 (d, J= 9 Hz, 1H), 7.46-7. 36 (m, 1H), 7.18-7. 08 (m, 1H), 7.00 (d, J = 9 Hz, 1H), 6.62-6. 50 (m, 2H), 2.60 (s, 3H), 2.55 (s, 3H).

Example 176: 1H NMR (CDCl3) d 8.15 (t, J = 9 Hz, 1H), 8.00 (s, 1H), 7.45-7. 35 (m, 1H), 7.32-7. 20 (m, 1H), 7.20-7. 05 (m, 3H), 6.80 (t, 1H), 6.50 (s, 1H), 4.65 (d, 2H), 2.65 (s, 3H), 2.50 (s, 3H).

Example 177: 1H NMR (CDCI3) d 8.20 (t, 1H), 7.90 (s, 1H), 7.50-7. 05 (m, 8H), 6.80 (s, 1H), 5.05-4. 90 (m, 2H), 3.80 (d, 1H), 3.45 (d, 1H), 3.00 (dd, 1H), 2.90 (dd, 1 H), 2.50 (s, 3H).

Example 181 : 1H NMR (300MHz, CDCl3) # 8.41 (s, 1H), 8. 28-8. 23 (d, 1H), 8.15 (s, 1H), 7.69-7. 60 (d, 1H), 7.62-7. 50 (m, 3H), 7.50-7. 47 (dd, 1H), 6.35 (s, 1 H), 5.36 (s, 1 H), 4.80 (s, 2H).

Example 184: 1H NMR (300MHz, CDC ! s) 008. 96-8.90 (s, 1H), 8.08 (s, 1H), 8.04 (d, 1 H), 7.72 (d, 1 H), 7.70-7. 61 (dd, 1 H), 7.24-7. 20 (dd, 1 H), 6.92-6. 84 (t, 1 H), 6.36 (s, 1 H), 4.96-4. 89 (d, 2H).

Example 186 : 1H NMR (300MHz, CDCI3) ##8. 96-8.90 (s, 1H), 8. 08 (s, 1H), 8.44 (s, 1 H), 8.27-8. 24 (d, 1 H), 8.02 (s, 1 H), 7. 78-7. 76 (d, 1 H), 7.73-7. 70 (d, 1 H), 7.58-7. 51 (m, 2H), 7.13-7. 08 (dd, 1 H), 5.51 (s, 2H).

Example 195: 1H NMR (CD30D) # 8.40 (s, 1H), 8.27 (d, 1H), 8.03 (s, 1H), 7.75- 7.50 (m, 2H), 6. 10 (s, 1H), 4.76 (s, 2H), 4.05 (m, 2H), 3.88 (m, 2H), 3.52 (m, 1H), 2.33 (m, 1H), 2.20 (m, 1H).

Example 196 : 1H NMR (CD30D) 8 8.73 (d, 1H), 8.58 (q, 1H), 8.12 (s, 1H), 8.00 (d, 1H), 7.54 (q, 1H), 6.19 (s, 1H), 4.86 (s, 2H), 4.22-4. 08 (m, 2H), 4.03-3. 93 (m, 2H), 3.63 (m, 1 H), 2.50-2. 39 (m, 1 H), 2.32-2. 21 (m, 1 H).

Example 197 :'H NMR (CD30D) 88. 73 (d, 1H), 8.58 (q, 1H), 8.12 (s, 1H), 8.00 (d, 1H), 7.54 (q, 1H), 6.19 (s, 1H), 4.86 (s, 2H), 4.22-4. 08 (m, 2H), 4.03-3. 93 (m, 2H), 3.63 (m, 1 H), 2.50-2. 39 (m, 1 H), 2.32-2. 21 (m, 1 H).

Example 199 :'H NMR (300MHz, CDC13) 0 08. 29 (s, 1H), 8.15 (brs, 1H), 7.95 (s, 1 H), 7.28 (d, 1 H), 7.05-6. 95 (appt t, 1 H), 5.70 (s, 1 H), 4.62 (d, 2H), 2.90 (m, 1 H), 2.30 (m, 1 H), 1.9-1. 2 (m, 8H), 0.65 (d, 3H).

Example 200 :'H NMR (300MHz, CDCl3) ## 8.71 (s, 2H), 8.00 (s, 1H), 6.13 (s, 1 H), 3.59 (s, 2H), 3.01-2. 58 (m, 1 H), 2.51-2. 45 (m, 1 H), 2.44-2. 30 (m, 1 H), 2.20 (s, 3H), 2.09-1. 95 (m, 2H), 1.85-1. 70 (m, 2H), 0.80-0. 76 (d, 3H).

Example 203 :'H NMR (300MHz, CDC13) 008. 10 (s, 1H), 8.08 (s, 1H), 6.27 (s, 2H), 4.95 (s, 2H), 3.00-2. 90 (dd, 2H), 2.60 (m, 2H), 2.48 (br s, 1 H), 2.39 (s, 3h), 2.25 m, 1 H), 1.95-1. 70 (m, 3H).

EXAMPLE 211: To a solution of the compound prepared in Example 156 (100 mg, 0.23 mmol) in dry THF (4 mL) was added LiAIH4 (1. 0 M in THF, 0.110 mL, 0.110 mmol) at 0°C under N2. The mixture was stirred at 0°C for 1 hr, warmed to 25°C, then additional LiAIH4 (1.0 M in THF, 0.400 mL) was added, the mixture was stirred for 20 min and then quenched with MeOH (2.0 mL). The solvent was evaporated and the crude product was purified by flash chromatography using 10: 1 CH2CI2 : MeOH as eluent. White solid (46 mg, 49%) was obtained. LCMS: M+= 416. Mp=71-72 °C.

EXAMPLE 212:

To a solution of the compound prepared in Example 156 (70 mg, 0.16 mmol) in dry THF (3 mL) was added MeMgBr (3.0 M in Et20, 1.10 mL, 3.20 mmol) under N2. The mixture was stirred at 25°C for 45 min and then quenched with saturated aqueous NH4C1 (5.0 mL). The mixture was poured into saturated aqueous NH4CI (30 mL) and extracted with CH2CI2 (3x20 mL). The extracts were dried over Na2SO4 and filtered. The solvent was evaporated and the crude product was purified by flash chromatography using 20: 1 CH2CI2 : MeOH as eluent. White solid (25 mg, 36%) was obtained. LCMS: M+= 444. Mp=76-80 °C.

EXAMPLE 213: Anhydrous DMF (40 mL) was added under N2 to the compound prepared in Preparative Example 174 (2.50 g, 8.65 mmol) and 60 % NaH in mineral oil (346 mg, 8.65 mmol). The mixture was stirred at 25°C for 1 hr, then 2-chloro-5- chloromethylpyridine N-oxide (1.54 g, 8.65 mmol) in anhydrous DMF (20 mL) was added slowly. The mixture was stirred at 25°C for 18 hr, the solvent was evaporated and the crude product was purified by flash chromatography using

30: 1 CH2CI2 : MeOH as eluent. So obtained solid was triturated by 50 mL of 1: 1 EtOAc: hexane. Pale yellow solid (1.25 g, 34%) was obtained. LCMS: MH+=432.

Mp=224-226°C.

EXAMPLES 214-217: By essentially the same procedure set forth in Example 213 combining the compounds shown in Column 2 of Table 19 with compounds in Column 3 of Table 19, the compounds shown in Column 3 of Table 19 were prepared.

TABLE 19 Ex. Column 2 Column 3 Column 4 CMPD 214 CI LEMS : N N MH+=380 ; mp=, c W N, N I N. NN O H2 HN /1 Yo NH2 ! cri Cl 215 i i CMS : N N MH+=450 ; mu=218- ', U 222°C F W N N O NH2 HN Zozo C) cl 216 i I /LCMS : N N MH+=466 ; tt Cl XN so w v X m1P2=81°2C6- T Cl HN) mu=126- co N /1 I I CI \ NO ce -Cl _ LC MS 217 \ I N Br (/N Br M+=523 i i N i ANTS NH2 HN. NHs HN N) --NTs EXAMPLE 218:

CF3CH20H (3.0 mL) was added under N2 to 60% NaH in mineral oil (40 mg, 1.0 mmol), the mixture was stirred for 20 min, then the product prepared in Example 213 (50 mg, 0.12 mmol) was added. The mixture was refluxed for 20 hr, the solvent was evaporated, and the residue was purified by flash chromatography using 20: 1 CH2CI2 : MeOH as eluent to yield pale yellow solid (35 mg, 61%). LCMS: M2H+=496. Mp=208-210°C.

EXAMPLES 219-225: By essentially the same procedure set forth in Example 218 combining the compounds shown in Column 1 of Table 20 with the appropriate alcohol, the compounds shown in Column 2 of Table 20 were prepared.

TABLE 20 I Ex. I Column 1 | Column 2 Data 219 ---_.. _ LCMS : N M+=426 ; mp=126- N-N N-N 1280C HAN H N IN ICI N, 0 N, 0 ce OCH3 220 Br Br LCMS : N N M+=483 ; mu=89- ploc ZON N-N N-N HO H II II N. N'O N C'-N---" 221 rR rfp. LCMS : N N M2H+=442 -yN N 'U 114°C 1140C HO. HN /1/1 IN ICI Ho han CI OCH2CH3 222 w CMS : N MH+=462 ; mp=121- 123oC HO H HO HAN N, N, II II CI \ N'O CI NO CI OCH3 223 Br Br LCMS : /N I/N MH =444 ; mp=l 12- zon F N-N F N-N 1140C HN H N XI C ! OCHs OH3 224 LCMS : /N i/N M+=376 ; mp=oc YNoN F SN_N HN HN 1 N, 0 N, 0 Cl OCH3 225 Br Br LCMS : /N I/N mp=, c YN-N F YN N HN HN I I NO N'O HN. HN CI 0 0 EXAMPLE 226:

A mixture of the product prepared in Example 213 (100 mg, 0.23 mmol) and KOH (95 mg, 1.70 mmol) in 1,2-dimethoxyethane (3mL) and H20 (1.5 mL) was refluxed under N2 for 20 hr, quenched with acetic acid (0.30 mL), and the solvent was evaporated. The residue was suspended in H20 (15 mL), filtered and the solid was washed with H20 (15 mL) and Et20 (10 mL). Then it was mixed with CH2CI2 (2 mL) and Et20 (2 mL) and filtered. Et20 (5 mL) was added to the filtrate and the mixture was allowed to stand overnight. The solid was removed by filtration, washed with Et20 and then dissolved in MeOH (5 mL).

The solution was filtered and the solvent from the filtrate was evaporated. Off- white solid (5 mg, 5%) was obtained. LCMS: M+=412. Mp= 206-208°C.

EXAMPLE 227:

A mixture of the product prepared in Example 213 (129 mg, 0.30 mmol), N, N-dimethylethylenediamine (0.165 mL, 1.50 mmol), and diisopropylethylamine (0.10 mL) in anhydrous N-methylpyrrolidinone (1.0 mL) was stirred at 100°C for

24 hr. The solvent was evaporated, and the residue was purified by flash chromatography using 20: 1 CHC12 : 7N NH3 in MeOH as eluent to yield pale yellow solid (110 mg, 76%). LCMS: M+=482. Mp=76-78°C.

EXAMPLES 228-233: By essentially the same procedure set forth in Example 227 combining the compounds shown in Column 1 of Table 21 with the appropriate amine, the compounds shown in Column 2 of Table 21 were prepared.

TABLE 21 Ex. Column 1 Column 2 Data 228 Br Br LCMS : M2H+=467 mol26- N N y N, N 128=°C HAN H ZU IN ICI 0 CRI 229 w cMS : N M+=481 ; mu=128- HN HN. N N HN HN HN H II II N, 0 N, 0 cl N c 0 230 Br Br LCMS : /N I/N M =494 ; -ton 'U 110°C HN. HN. HO HAN N I I CHs cl (N) N CH3 231 X w LCMS : N N M2H+=482 ; mu=129- 133oC Ho han ho H N CI CN\ . Box Boc boy ; mu=924- N N M2H+=482 N_N iN_N 126°C N N HN HN Zu (N) N CRI N H N H 233 Br Br LCMS : JL N j J. N J M2H471 N N M2H+=471 % \ ; mp=88- 90oC N-N N-N gooc HN H N In il N. NO ci H3CO~ EXAMPLE 234:

A mixture of the product prepared in Example 213 (80 mg, 0.19 mmol) and 2.0 M methylamine in THF was stirred in a closed pressure vessel at 50°C for 72 hr. The solvent was evaporated, and the residue was purified by flash chromatography using 10: 1 CH2Cl2 : MeOH as eluent to yield pale yellow solid (40 mg, 51%). LCMS: M2H+=427. Mp=217-219°C.

EXAMPLE 235: By essentially the same procedure set forth in Example 234, the compound shown above was prepared. LCMS: M2H+=441. Mp=98-101 °C.

EXAMPLE 236:

The compound prepared in Preparative Example 174 (140 mg, 0.48 mmol) and the aldehyde (71 mg, 0.58 mmol) were stirred in anhydrous THF (4 mL) at 50°C under N2. Ti (OiPr) 4 (0.574 mL, 1.92 mmol) was added, the mixture was stirred at 50°C 3 hr, and cooled to 25°C. NaBH3CN (181 mg, 2. 88 mmol) was added, the mixture was stirred for 2 more hr, then poured into 10 % aqueous Na2CO3 (100 mL), and extracted with CH2CI2 (3 x 50 mL). Combined extracts were dried over Na2SO4, filtered, and the solvent was evaporated. The residue was purified by flash chromatography using 15: 1 CH2CI2 : MeOH as eluent to yield pale yellow solid (40 mg, 21%). LCMS: MH+=398. Mp>230 °C.

EXAMPLES 237-256: By essentially the same procedure set forth in Example 236 combining the compounds shown in Column 2 and 3 of Table 22, the compounds shown in Column 4 of Table 22 were prepared.

TABLE 22 Ex. Column 2 Column 3 Column 4 Data 237 fez CHO Br LCMS : M+=381 ; WNHN-N N<N YNoN -yin NU2 HAN H2 ION NON 238 rp,"CH<3. LCMS : L i N L L JL N =387 ; 238 Br CHO Br LCMS : M =387 ; N N MP=OC 0-yin- NON H2 ho N Nz N N MH+=413 ; MH+=413 ; /N\ ( N mp=157- Oye NH2 OCH3 HN non NON OCH3 240 CHO LCMS : [. L M k L 1 M M2H=419 Br Br M2H+=419 N N mu=77- N N N, i 79°C N N OCH3 HN H2 NON OCH3 241 Br CHO Br LCMS : M2H+=385 /N N w/1 r rpp=14- 'l 216°C N_N N ! NN NH2 HNa --N N 242 CHO LCMS : bu ber W I/N mP oC zon \ N N N-N MP NHs OCH3 HN \ N OCH3 243 Br CHO Br LCMS : M =416 ; N'_ l I w N'l mP=0_ Mu=80- N-N N N-N 820C NH2 OCH3 HN N OCI N OCH3 244 Br CHO Br Bu NHs "3 HN. H2 H N1, LOCHS zizi _ NHs HN. TsN-N CHO bu zon NHs HN. H2 HN Ton 246 I W Br CHO LCMS : N N N N N N'N H2 HN zon I O 247 I Br CHO\ LCMS : N N MH+= 401 ; mp>2000C zon F SN_N NoN F SN_N H2 HN N, N N N Y rS : = Br /N I I N 4 4 ;- ' l mp>200. 0. 'C dec. H2 0 HN '. N 0 I I N O 249 Br CHO Br LCMS : IN Br N'/N'l mp= 65- N N,, N N 670C NH2 OCH3 HNa 2 oc3 NON LOCHS oc3 250 O CH p LCMS : Br N M2H+=421 ; mp=87- N-N N yN N-N 930C \ N, N Y \ NN H2 OCH3 HN Non NN OCH3 251 CHO LCMS : M H+=361 ; /N W W N mp>225°C WN_N NtN WN_N L M NN L J. NH2 OCH3 HN ICI NON OCHs OCH3 252 CHO LCMS : N N MH+=346 ; my=270- N N r 271 OC N ou NH2 HN N OH 253 Br CHO Br LCMS : Mu =402 ; mp=250- 2550C N'N N OH N'N H2 HO N OH I I N"OH 254 Br CHO Br LCMS : MH =416 ; mp=210- N-N F N-N 21 50C NHz HN. N OU 255 Br CHO Br LCMS : Br MH+=428 ; -yN F N-N N F N-N mp=145cC NH2 HN F N, N F NN H2 OCH3 HN N OCH3 256 B CHO Br LCMS : p N N I w O N N mp oC 'l N N otN4, N N 0 N N MH+= ; on YN-N NtN °) WN-N , + NH2 OCH3 A, HN N, NON LOCHS OC3 OCH3 EXAMPLE 257 :

A mixture of the compound prepared in Example 242 (100 mg, 0.24 mmol), conc. aqueous HCI (1.0 mL) and acetic acid (2.0 mL) were stirred at 100°C under N2for 2 hr, then poured onto Na2CO3 (15 g), and extracted with 1: 1 acetone: CH2CI2 (3 x 30 mL). Combined extracts were filtered, and the solvent was evaporated. The residue was purified by flash chromatography using 10: 1 CH2CI2 : MeOH as eluent to yield pale yellow solid (36 mg, 37%). LCMS: M2H+=398.

EXAMPLES 258-260: By essentially the same procedure set forth in Example 257 starting from the compounds shown in Column 1 of Table 23, the compounds shown in Column 2 of Table 23 were prepared.

TABLE 23 Ex. Column 1 Column 2 Data 258 Br Br LCMS : N M =402 ; fol, mi=229- N, N N'N z HN HN N I \NH N NH T T OCH3 259 A Br A Br MLHC=M4S 6 ; mu=215 -yin 2180C F N, N F N, N HO HAN NU Y ho han OCH 0 LCMS : 260 N Br M2H+=398 JL N/ J. N/M2H398 '/, mp>230°C -YN-N HN HN Y HO HAN N NH 0 0 EXAMPLE 261:

To a stirred solution of the compound prepared in Example 239 (41 mg, 0.10 mmol) in CH2CI2 was added 1.0 M BBr3 (0.30 mL, 0.30 mmol) in CH2Cl2 at- 78°C. The mixture was stirred at-78°C for 5 min, then at 24°C for 3 hr, then MeOH (2.0 mL) was added and the mixture was stirred for 10 min. The solvent was evaporated and the residue was purified by flash chromatography using 5: 1: 0.1 CH2CI2 : MeOH: conc. NH40H as eluent to yield white solid (39 mg, 99%).

LCMS: M+=397. Mp>230 °C.

EXAMPLE 262:

A mixture of the product prepared in Example 217 (40 mg, 0.077 mmol) and 5.0 M aqueous NaOH (0.8 mL) in MeOH (3.0 mL) was refluxed under N2 for 1 hr. NaHC03 (700 mg) was added, the solvent evaporated, and the residue was purified by flash chromatography using 10: 1: 0.1 CH2CI2 : MeOH : conc. NH40H as eluent to yield white solid (10 mg, 35%). LCMS: M2H+=371.

Mp=237-239°C.

EXAMPLES 263-264: By essentially the same procedure set forth in Example 262 starting from the compounds shown in Column 1 of Table 24, the compounds shown in Column 2 of Table 24 were prepared.

TABLE 24 Ex. Column 1 Column 2 Data 263 i. LCMS : \ N Br N Br M2H+=370 N mu=166- 1680C N N N-N HNJ HNJ TsN HN 264 Br Br LCMS : M22H =371 ) :"I ; mp=180- '°C W NN N'N HO HAN TsN-N HN N EXAMPLE 265:

TFA (0.5 mL) was added to a solution of the compound prepared in Preparative Example 197 (0.08 g, 0.16 mmol) in CH2CI2 (2.0 mL) at 0°C and the resulting solution stirred 2.5 hours and stored at 4°C overnight at which time additional TFA (0.5 mL) was added. The resulting solution was stirred 4 hours and concentrated in vacuo. The residue was neutralized with 1 N NaOH and extracted with CH2Cl2. The combined organics were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by flash chromatography using a 2.5% (10% NH40H in MeOH) in CH2CI2 solution as eluent (0.009 g, 15% yield). LCMS: MH+=396 ; mp= 53-54°C.

EXAMPLE 266:

A solution of the compound prepared in Preparative Example 182 (26 mg, 0.070 mmol) and potassium thiocyanate (13 mg, 0.14 mmol) in MeOH (1 mL) was cooled in a cold water bath. To it was added a solution of bromine (22 mg, 0. 14mmol) in MeOH (0.7 mL) dropwise. The resulting reaction mixture was stirred for 4 h at room temperature and the volatiles were removed under reduced pressure. The residue obtained was suspended in a small amount of CH2Ci2. The potassium bromide was filtered off and pH of the filtrate was adjusted to about 7 by the addition of aqueous ammonia. It was concentrated under reduced pressure and the residual oil was purified by preparative thin- layer chromatography using 15% MeOH in CH2CI2 as eluent (26 mg, 87% yield).

'H NMR (CDC13) 8 8.75 (d, J = 4.2 Hz, 2H), 8.38 (s, 1 H), 7.68-7. 64 (m, 2H), 7.46- 7.39 (m, 3H), 7.22 (t, J = 6.3 Hz, 1 H), 6.43 (s, 1 H), 4.84 (d, J = 6.3 Hz, 2H); LCMS: MH+ = 427.

EXAMPLE 267: Boron tribromide (1 M in CH2CI2, 0.60 mL, 0.60 mmol) was added dropwise to an ice-cold stirred solution of the compound prepared in Example 24 (50 mg, 0.12 mmol) in CH2CI2 (1.5 mL) under an argon atmosphere. The

resulting reaction mixture was stirred at 0°C for 30 minutes, allowed to warm up to room temperature, and stirred overnight. The mixture was quenched by the addition of a small amount of water and extracted with CH2CI2. The organic layer was dried over magnesium sulfate and concentrated in vacuo (45 mg, 94% yield). 1H NMR (CD30D) 8 9. 16 (s, 1H), 8.95 (s, 1 H), 8.88 (d, J = 8.1 Hz, 1H), 8.24 (t, J = 6. 9 Hz, 1H), 8.18 (s, 1H), 7.95 (d, J = 7. 8 Hz, 1H), 7.40 (t, J = 7. 8 Hz, 1 H), 7.00-6. 96 (m, 2H), 6.86 (s, 1 H), 5.28 (s, 2H) ; LCMS : MH+ = 396.

EXAMPLE 268 : A solution of the compound from Preparative Example 184 (0.05 g, 0.15 mmol), N-methylpiperazine (20 µL, 1.2 eq. ) and iPr2Et (52 pL, 2.0 eq. ) in dioxane (1 mL) was heated to 70 °C overnight. The reaction mixture was cooled to room temperature and diluted with H20 and saturated NaHCO3. The resulting mixture was extracted with CH2CI2, the combined organics dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by Preparative TLC using a 5% (10% NH40H in MeOH) in CH2CI2 solution as eluent (0.028 g, 47% yield). MS: MH+= 402. mp = 210 °C (dec. ) EXAMPLES 269-275: By essentially the same procedure set forth in Example 268 only substituting the amine in Column 2 of Table 25 and the chlorides in Column 3 of Table 25, the compounds shown in Column 4 of Table 25 are prepared: TABLE 25 Ex. Column2 Column 3 Column 4 CMPD 269 Bu ber MS : MH+ ci NY_ N 387 ON H ON m. p. 182- \ NN 183°C HN HN IN IN I \ N N 270 Br n Br MS : MH+- N N \ (373 N M. P. 190- \ NN 191 C HN HN HO HAN \ N N 271 Br Br MS : MH = , Zon H m. p. 20 7- \ NN OH N, N 230 C HN HN HO HAN N N 272 HN Br HN MS : MH+= CI N (N N Bf 388 m. p. 198- 201 OC HAN HAN HN IN N N N MS : MH+ _ 273 HN CI N Br H N Br 430 .. kNH Y N NV . 03 MS437 " H -r 'I Nz 274 Br MS : MH+ _ CI N N 456 Br m. p. 175- NN N N 178 °C N HAN H HO N/ N N 275 Br Br MS : MH+ _ CI N N N 403 0 JDNH N N-1 HO HO P -FrN N HN HAN HAN IN IN EXAMPLE 276: Step A:

4-Fluorophenyl magnesium bromide (0.68 mL, 1.2 eq. ) was added to the compound prepared in Preparative Example 193 (0. 20 g, 0.55 mmol) and PdCl2 (dppf) 2 (0.037 g, 10 mol%) in THF and the resulting solution was stirred at room temperature 72 hours. The reaction mixture was dilute with saturated NH4CI and extracted with EtOAc. The combined organics were washed with saturated NaCI, dried over Na2SO4, filtered and concentrated. The crude product was purified by flash chromatography using neat EtOAc as eluent (0.15 g, 65% yield). MS: MH+ = 420.

Step B: By essentially the same procedure set forth in Preparative Example 127 only substituting the compound prepared in Example 276, Step A, the above compound was prepared (0.17 g, 94% yield).

Step C: By essentially the same procedure set forth in Preparative Example 200 only substituting the compound prepared in Example 276, Step B, the above compound was prepared (0. 1g, 100% yield).

Step D:

By essentially the same procedure set forth in Example 265 only substituting the compound prepared in Example 276, Step C, the above compound was prepared (0.049 g, 62% yield). MS: MH+ = 414; mp = 110-115 °C.

EXAMPLE 277: Step A:

Pd (PPh3) 4 (0.065 g, 10 mol%) was added to 3-cyanophenyl zinc iodide (2.2 mL, 0.5 M solution in THF, 2 eq. ) and the compound prepared in Preparative Example 193 (0.2 g, 0.56 mmol) in DMF (2.0 mL) and the resulting solution heated to 80 °C g for 144 hours. The reaction mixture was cooled to room temperature, diluted with saturated NH4CI and extracted with EtOAc. The combined organics were washed with H20 and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by flash chromatography using a neat EtOAC solution as eluent (0.07 g, 29% yield).

MS: Mu'= 427.

Step B through Step D:

By essentially the same procedures set forth in Example 276, Step B through Step D, the above compound was prepared (0.023 g, 53% yield). MS: MH = 421; mp = 230 °C (dec. ) EXAMPLE 278:

By essentially the same procedure set forth in Example 276 only substituting the appropriate cyclopropylmagnesium bromide in Step A, the compound was prepared. MS: MH+ = 372; m. p. = 96-98 °C.

EXAMPLE 279:

The palladium-catalyzed zinc cross-coupling reaction was carried out in a manner similar to the procedure described in J. Org. Chem. (1999), 453. A solution of the chloropyrazolopyrimidine (200 mg, 0.458 mmol), Pd (PPh3) 4 (53

mg, 0.046 mmol), and exo-2-norbonylzinc bromide (0. 5 M in THF, 0.95 mL, 0.47 mmol) in DMF (2 mL) was refluxed at 100°C (oil bath temp. ) overnight. The reaction mixture was quenched with half-saturated NH4CI and extracted with CH2CI2. The organic phase was dried over MgS04 and concentrated under reduced pressure. The residue was purified by flash chromatography using a 50% EtOAc in hexanes solution as eluent. A solution of the obtained N-Boc- protected product (121 mg, 53% yield, LCMS: MH+ = 498) and TFA (1 mL) in CH2CI2 (2 mL) was stirred at room temperature for 2 hr. The volatiles were removed under reduced pressure. The residue was dissolved in CH2CI2, neutralized with saturated NaHC03, and extracted with CH2CI2. The organic phase was dried over MgS04 and concentrated in vacuo (96 mg, 99% yield).

LCMS: MH+= 398 ; H NMR (CDCI3) 8 8. 78 (s, 1 H), 8.71 (d, J = 4.2 Hz, 1 H), 8.04 (d, J = 3.9 Hz, 1H), 7.80 (d, J = 7. 8 Hz, 1H), 7.44 (m, 1H), 6.73 (m, 1H), 5.98 (d, J = 7. 5 Hz, 1 H), 4.74 (d, J = 5.4 Hz, 2H), 3.40-1. 00 (m, 11 H).

EXAMPLES 280-294: By following essentially the same procedure set forth in Example 279 only substituting the chlorides shown in Column 2 of Table 26 and the organozinc reagents shown in Column 3 of Table 26, the compounds in Column 4 of Table 26 were prepared: Table 26 Ex. Column 2 Column 3 Column 4 Data 280 Br Me Me LCMS : MH = 395 CI N I I Br ton t w N, N W NN r. N. 1 Boc'N HN I N I N 281 Br Me Me LCMS : MH+ = 400 Cl"0 Znl S N Br LjO'Sz.. S w N, N Boc'tN HN N ZON N 282 Br F F LCMS : MHT = 412 Cl,, N Br nez D) , han ZON HAN /1 I I uhr 283 Br/C02Et, COEt LCMS : MHT = 452 CI N I Br N ZnBr N NN Boc'N HN N ZIZI N 284 Br LCMS : MH"=422 i i CRI N N N N Boc'N HN N N 285 Br | Br LCMS : MH = 408 CI N //I ZnBr I N i w N_N / BOczN) HN) 4 n IN IN 286 Br Me02C gr LCMS : MH+ 404 CI N ZnBr Me02C N W NN Han Boc'N fb n WN tN 287 Br MeO2C Br LCMS : MH+ = 404 N N N N-N HN Boc'N fb n N N 288 Br LCMS : MH+ 408 ct. N. y r) t f if j CI N Br /'nul Zon N-N N-N Boc'N HN /zizi N N 289 Br Br LCMS : MH+ = 386 S i N ZnBr w N, N NN Boc N HN IN IN N N 290 Br Br Br LCMS : Mu+= 464 Cl,, N ZnBr S N N XN NON 'N r ZON w N l N 291 Br Br Br LCMS : MH = 480 C'NJ/Y Br Cl N Br X-NBr Boc'r N-N Boc'N HN N +, 0- I I 292 Br LCMS : MH"=424 CI N Ber Nui Znl W Nz N BOC"' HN. LN+. til Boc'N HN 293 Br Br LCMS : MH+ = 424 Cl-rN ZnBr NN-N w N, N/ NN Boc'N HN N In il N _ 294 Br SMe LCMS : MH'= 426 Boc'N HN Znl W Nz SMe w N, N Boc N HN I N ICI \ N

Additional data for select compounds is shown below.

EXAMPLE 280 : 1H NMR (CDC13) 8 8.65 (s, 1H), 8. 57 (d, J = 4.2 Hz, 1H), 8.50 (d, J = 4.5 Hz, 1H), 8.01 (s, 1H), 7.69 (d, J = 7.5 Hz, 1H), 7.61 (d, J = 7.8 Hz, 1H), 7.31-7. 22 (m, 2H), 6.77 (m, 2H), 4.71 (d, J = 5.4 Hz, 2H), 2.68 (s, 3H).

EXAMPLE 281 :'H NMR (CDC13) # 8.80 (s, 1 H), 8.72 (d, J = 4.8 Hz, 1 H), 8.08 (s, 1H), 7.85-7. 40 (m, 3H), 7.02 (d, J = 5.1 Hz, 1H), 6.90 (t, J = 6. 0 Hz, 1H), 6.29 (s, 1 H), 4.79 (d, J = 6.0 Hz, 2H), 2.61 (s, 3H).

EXAMPLE 282 : 1H NMR (CDCl3) # 8.67 (s, 1 H), 8.61 (d, J = 3. 9 Hz, 1 H), 8.03 (s, 1 H), 7.72-7. 31 (m, 3H), 7.22-7. 00 (m, 2H), 6. 81 (t, J = 6.0 Hz, 1 H), 6.03 (s, 1 H), 4.68 (d, J = 6.0 Hz, 2H), 2.28 (s, 3H).

EXAMPLE 283 : 1 H NMR (CDCl3) # 8.68 (s, 1 H), 8.63 (d, J = 4.0 Hz, 1 H), 8.00 (s, 1 H), 7.80-7. 72 (m, 2H), 7.54-7. 47 (m, 3H), 7.35 (m, 1 H), 6.74 (t, J = 6.0 Hz, 1 H), 6.19 (s, 1H), 4.67 (d, J = 6. 0 Hz, 2H), 4.21 (q, J = 7. 2 Hz, 2H), 1.13 (t, J = 7. 2 Hz, 3H).

EXAMPLE 284: 1H NMR (CDC13) 5 7.97 (s, 1H), 7.65 (d, J = 7.2 Hz, 1H), 7.33- 7.15 (m, 5H), 6.73 (t, J = 5.4 Hz, 1H), 5.99 (s, 1H), 4.61 (d, J = 5. 4 Hz, 2H), 3.09 (sept, J = 6.9 Hz, 1 H), 1.11 (d, J = 6.9 Hz, 6H).

EXAMPLE 285 : 1H NMR (CDC13) # 8.56-8. 55 (m, 2H), 7.94 (s, 1H), 7.54 (m, 1H), 7.30-7. 22 (m, 6H), 6.59 (t, J = 5.7 Hz, 1H), 5.66 (s, 1H), 4.47 (d, J = 5. 7 Hz, 2H), 4.26 (q, J = 7.2 Hz, 1 H), 1.68 (d, J = 7.2 Hz, 3H).

EXAMPLE 286 : 1H NMR (CDC13) 8 8.67 (m, 2H), 7.94 (s, 1H), 7.69 (d, J = 7.8 Hz, 1H), 7.34 (m, 1H), 6.63 (t, J = 5.7 Hz, 1H), 5.87 (s, 1H), 4.62 (d, J = 5. 7 Hz, 2H), 3.64 (s, 3H), 3.13 (m, 2H), 2.82 (m, 1H), 1.22 (m, 3H).

EXAMPLE 287 : 1H NMR (CDCl3) # 8.66 (m, 2H), 7.94 (s, 1 H), 7.68 (d, J = 7.8 Hz, 1H), 7.34 (m, 1H), 6.62 (t, J = 6.0 Hz, 1H), 5.87 (s, 1H), 4.62 (d, J = 6. 0 Hz, 2H), 3.64 (s, 3H), 3.13 (m, 2H), 2.81 (m, 1H), 1.22 (m, 3H).

EXAMPLE 288 :'H NMR (CDC13) # 8.64 (s, 1H), 8.60 (d, J = 3.6 Hz, 1H), 8.04 (s, 1H), 7.68 (m, 1H), 7.31 (m, 1H), 7.16 (m, 1H), 7.07-7. 05 (m, 2H), 6.80 (t, J = 6.3 Hz, 1 H), 5.93 (s, 1 H), 4.64 (d, J = 6.3 Hz, 2H), 2.08 (s, 6H).

EXAMPLE 289: 1H NMR (CDCl3) # 8.72 (s, 1H), 8.62 (d, J = 4. 8 Hz, 1H), 7.99- 7. 97 (m, 2H), 7.73-7. 69 (m, 2H), 7.40-7. 33 (m, 2H), 6.67 (t, J = 6.0 Hz, 1 H), 6.29 (s, 1H), 4.71 (d, J=6. 0Hz, 2H).

EXAMPLE 290 : 1H NMR (CDC13) # 8.73 (s, 1 H), 8.62 (d, J = 4.5 Hz, 1 H), 8.01 (s, 1 H), 7.76 (m, 1 H), 7.41 (d, J = 5.1 Hz, 1 H), 7.34 (dd, J = 8.1, 5.1 Hz, 1 H), 7.05 (d, J = 5.1 Hz, 1 H), 7.01 (s, 1 H), 6.79 (t, J = 6.0 Hz, 1 H), 4.74 (d, J = 6.0 Hz, 2H).

EXAMPLE 291 :'H NMR (DMSO-d6) 8 9.12 (s, 1H), 8.40 (s, 1H), 8.33 (s, 1H), 8. 13 (m, 1H), 7. 82 (d, J = 5. 1 Hz, 1H), 7.40-7. 39 (m, 2H), 7.22 (d, J = 5. 1 Hz, 1H), 6.86 (s, 1H), 4.86 (s, 2H).

EXAMPLE 292: 1H NMR (CDC13) 8 8. 23 (s, 1H), 8.16 (d, J = 6.0 Hz, 1H), 8. 06 (s, 1 H), 7.31-7. 05 (m, 5H), 6.86 (m, 1 H), 5.87 (s, 1 H), 4.62 (d, J = 6.3 Hz, 2H), 2.09 (s, 6H).

EXAMPLE 293 : 1H NMR (CDCl3) # 8.14 (s, 1H), 8.12 (d, J = 6.3 Hz, 1H), 7.94 (s, 1H), 7.29-7. 16 (m, 6H), 7.07 (m, 1H), 6.78 (t, J = 6.0 Hz, 1H), 5.54 (s, 1H), 4.44 (d, J = 6. 0 Hz, 2H), 4.24 (t, J = 7. 2 Hz, 1 H), 1.68 (d, J = 7. 2 Hz, 3H).

EXAMPLE 294 : 1H NMR (CDCI3) 8 8. 67 (s, 1H), 8. 59 (d, J = 4.8 Hz, 1 H), 8. 01 (s, 1H), 7.71 (m, 1H), 7.52 (dd, J = 7.8, 1.8 Hz, 1H), 7.40-7. 19 (m, 4H), 6. 78 (t, J = 6.0 Hz, 1 H), 6.32 (s, 1 H), 4.67 (d, J = 6.0 Hz, 2H), 2.38 (s, 3H).

EXAMPLE 295:

To a suspension of lithium aluminum hydride (10 mg, 0.26 mmol) in anhydrous THF (2 mL) at 0°C was added dropwise a solution of the compound prepared in Example 283 (20 mg, 0.044 mmol) in anhydrous THF (2 mL). The resulting mixture was refluxed for 1 hr and stirred at room temperature overnight, neutralized with dilute sulfuric acid, and extracted with EtOAc. The organic phase was dried over MgS04 and concentrated under reduced pressure. The crude product was purified by preparative thin-layer chromatography using a 5% MeOH in EtOAc solution as eluent (15 mg, 83% yield). LCMS: MH+= 410 ; H NMR (CDCI3) 8 8.69 (s, 1H), 8. 61 (d, J = 3.9 Hz, 1H), 8.05 (d, J = 2.1 Hz, 1H), 7.74 (d, J = 7.8 Hz, 1 H), 7.52-7. 31 (m, 5H), 6.97 (t, J = 6.3 Hz, 1 H), 6.55 (d, J = 2.7 Hz, 1 H), 6.20 (s, 1H), 4.71 (d, J = 6.3 Hz, 2H), 4.52 (s, 2H).

EXAMPLE 296: To a solution of the N-Boc-protected compound prepared in Example 294 (45 mg, 0. 085 mmol) in CH2CI2 (4 mL) at-50°C was added m-CPBA (18 mg, 0.10 mmol). After stirring for I hr at-50°C more m-CPBA (4 mg, 0.02 mmol) was added. The mixture was stirred for a further 2 hr, diluted with CH2Cl2 (20 mL), and washed with saturated NaHC03 (20 mL). The organic phase was dried over MgS04 and concentrated under reduced pressure. The residue was purified by preparative thin-layer chromatography using a 2.5% MeOH in CH2CI2 solution as eluent. A solution of the obtained N-Boc-protected product (37 mg, 80% yield, LCMS : MH+ = 542) and TFA (1 mL) in CH2CI2 (2 mL) was stirred at room temperature for 2 hr. The volatiles were removed under reduced pressure. The residue was dissolved in CH2CI2, neutralized with saturated NaHC03, and

extracted with CH2CI2. The organic phase was dried over MgS04 and concentrated under reduced pressure. The crude product was purified by preparative thin-layer chromatography using a 5% MeOH in EtOAc solution as eluent (26 mg, 89% yield). LCMS: MH+= 442 ; H NMR (CDC ! s) 8 8.71 (s, 1 H), 8.64 (d, J = 3.9 Hz, 1 H), 8. 41 (m, 1 H), 8.03 (s, 1 H), 7.75-7. 54 (m, 4H), 7.36 (dd, J = 8.1, 5.1 Hz, 1H), 6.81 (t, J = 6.0 Hz, 1H), 6.34 (s, 1H), 4.74 (d, J = 6.0 Hz, 2H), 3.25 (s, 3H).

EXAMPLE 297: To a solution of the N-Boc-protected compound prepared in Example 294 (56 mg, 0.11 mmol) in CH2CI2 (4 mL) at 0°C was added m-CPBA (42 mg, 0.24 mmol). After stirring for 2 hr at room temperature more m-CPBA (13 mg, 0.075 mmol) was added. The mixture was stirred at room temperature overnight, diluted with CH2CI2 (20 mL), and washed with saturated NaHC03 (20 mL). The organic phase was dried over MgSO4 and concentrated under reduced pressure. The residue was purified by preparative thin-layer chromatography using a 2.5% MeOH in EtOAc solution as eluent. A solution of the obtained N-Boc-protected product (29 mg, 49% yield, LCMS: MH+ = 558) and TFA (1 mL) in CH2CI2 (2 mL) was stirred at room temperature for 2 hr. The volatiles were removed under reduced pressure. The residue was dissolved in CH2CI2, neutralized with saturated NaHC03, and extracted with CH2Cl2. The organic phase was dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by preparative thin-layer chromatography using a 2.5% MeOH in EtOAc solution as eluent (21 mg, 90% yield). LCMS: MH+= 458 ; H NMR (CDCI3) 8 8.64 (s, 2H), 8.20 (m, 1 H), 8.01 (s, 1 H), 7.73-7. 60 (m, 3H), 7.46 (m, 1 H), 7.35 (s, 1 H), 6.82 (t, J = 5.9 Hz, 1H), 6.17 (s, 1H), 4.65 (d, J = 5.7 Hz, 2H), 3.60 (s, 3H).

EXAMPLE 298

By essentially the same procedure set forth in Preparative Example 127 only substituting the compound prepared in Preparative Example 189, the above compound was prepared. MS: MH+ = 334; mp = 170-173 °C.

Examples 299-300: By essentially the same procedure set forth in Example 298 only substituting the compound shown in Table 27, Column 2, the compounds shown in Table 27, Column 3 were prepared: Table 27 Ex. Column 2 Column 3 CMPD 299 Br MS : MH+ = 348 HO N HO N m. p. = 73-83 °C HO HAN HN. HN I I N N 300 Br MS : Mu'= 362 Ho HO N m. p. = 165-175 °C i N N N-N HN HN HN HN EXAMPLE 301:

To a solution of the compound prepared in Preparative Example 186 (0.1 g, 0.21 mmol) in THF (4.0 mL) at-78 °C was added nBuLi (0.57 mL, 2.16M in hexanes, 5.0 eq. ) at-78 °C. The reaction mixture was stirred 2 hours at-78 °C, quenched with H20, warmed to room temperature, and extracted with EtOAc.

The combined organics were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by Preparative TLC using a 2.5% (10% NH40H in CH30H) solution in CH2CI2 as eluent (0.013 g, 20% yield).

MS: Mu'= 326 ; mp = 71-72 °C.

EXAMPLE 302:

By essentially the same procedure set forth in Example 301 only substituting the compound from Preparative Example 187, the above compound was prepared (0.049 g, 68% yield). MS: Mu+ = 344; mp = 69-71 °C.

EXAMPLE 303:

To a solution of 3-H adduct from Preparative Example 187.1 (0.70 g, 2.32 mmol) in DMF (4.2 mL) at 0 °C was added POCI3 (0.67 mL, 7.2 mmol) dropwise.

The mixture was stirred for 14h at rt, cooled to 0 °C, and was quenched by addition of ice. 1 N NaOH was carefully added to adjust pH to 8 and the mixture was extracted with CH2CI2 (3 x 25 mL). The organic layers were combined, dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude product was recrystallized from EtOAc to afford 0.43 g (56%) of a yellow solid. mp 181-183 °C ; M+H = 330.

EXAMPLE 304: /O H/ 'STEP A i 9 STEP B Yv HN HN //1 II II N N STEP A: To a solution of aldehyde (100 mg, 0.30 mmoi) from Example 303 in THF (1 mL) at 0 °C was added cyclohexyl magnesium bromide (0.46 mL, 2. 0M in Et2O) dropwise over 5 min. The resulting mixture was stirred at 0 °C for 2h and at rt for 12h. The mixture was cooled to 0 °C and was treated with sat. aq.

NH4CI (3 mL) and CH2CI2 (5 mL). The layers were separated and the aqueous layer was extracted with CH2CI2 (2 x 5 mL). The organic layers were combined, washed with brine (1 x 5 mL), dried (Na2SO4), filtered and concentrated under

reduced pressure to afford 110 mg (89%) of a light yellow semisolid. M+H = 414.

This material was carried on crude to Step B without further purification.

STEP B: To a solution of alcohol (53 mg, 0.13 mmol) in CH2CI2 (0.5 mL) at 0 °C was added Et3SiH (24 pL, 0.15 mmol) followed by TFA (24 pL, 0.30 mmol). The mixture was stirred for 2 h at 0 °C and rt for 2 h whereupon additional portions of Et3SiH (24 pL, 0.15 mmol) and TFA (24 pL, 0.30 mmol) were added and the mixture was stirred for 3 h at rt (until complete by TLC). The mixture was concentrated under reduced pressure and the crude residue was partitioned between CH2CI2 (5 mL) and sat. aq. NaHC03 (2.5 mL). The layers were separated and the aqueous layer was extracted with CH2CI2 (2 x 5 mL). The organic layers were combined, washed with brine (1 x 5 mL), dried (Na2SO4), filtered and concentrated under reduced pressure. The crude product was purified by prep TLC (8 x 1000 mM) eluting with CH2CI2/MeOH (22: 1) to afford 29 mg (56%) of a yellow semisolid. M+H = 398.

EXAMPLES 305-312: By essentially the same procedure set forth in Example 304, utilizing the aldehyde from Example 303 and substituting the Grignard or organolithium reagents shown in Column 2 of Table 28, the compounds in Column 3 of Table 28 were prepared: TABLE 28 Ex. Column 2 Column 3 CMPD (Organometallic) (Final Structure) 1. mp (°C) 2. M+H 305 1. yellow MCIBr I oil '" han. kan zu /1 HAN 306 306 = MgBr 1. red oil 2. MH 353 Nz HN ZON 307 s 307-- 307 Li N 1. red oil 2. MH zon \/ N, N. 398 HN N N 308 1 yellow mgcl oil 2. M+H N 406 zon iN_N HN N N 309 Br N 1. yellow Y semisolid N N 2. M+H 384 HN N N 310 =--MgBr 1 semisolid N-N 340 31 1 XMgCI, N X 141 1m4P3 312 MgCI X 1. mp = N'N 340 HN N 311 Mgy, 1. mu zon LEZ 2. M+H- 358 HN ZON N 312 --MgCi N 1. mp 148-150 Zon ) 372 HO kan I I N EXAMPLE 313:

To solution of aldehyde (81 mg, 0.25 mmol) from Example 303 in benzene (2.5 mL) was added carboethoxymethylene triphenyl phosphorane

(0.12 g, 0.33 mmol) in one portion. The mixture was heated at reflux for 24h, cooled to rt, and concentrated under reduced pressure. The mixture was diluted CH2CI2 (5 mL), brine (2 mL) was added, and the layers were separated. The aqueous layer was extracted with CH2CI2 (2 x 4 mL). The organic layers were combined, dried (Na2SO4), filtered, and concentrated under reduced pressure.

The crude product was purified by preparative TLC (8 x 1000 M) eluting with CH2CI2/MeOH (20: 1) to afford 98 mg (100%) of white solid. mp 151-153 °C ; M+H = 400.

EXAMPLE 314: To a mixture of benzyltriphenylphosphonium bromide (0.59 g, 1.37 mmol) in THF (3 mL) was added NaH (55 mg, 1.37 mmol) and the mixture was stirred for 30 min. The aldehyde (0.15 g, 0.46 mmol) from Example 303 was added in a single portion and the mixture was heated at reflux for 36h. The mixture was cooled to rt and was concentrated under reduced pressure. The mixture was diluted CH2Cl2 (5 mL), brine (2 mL) was added, and the layers were separated.

The aqueous layer was extracted with CH2CI2 (2 x 4 mL). The organic layers were combined, dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude product was purified by preparative TLC (8 x 1000 pu) eluting with CH2CI2/MeOH (20: 1) to afford 58 mg (32%) of yellow solid. mp 138- 141 °C ; M+H = 404.

EXAMPLE 315:

To a solution of aldehyde (0.20 g, 0.60 mmol) from Example 303 in THF (3 mL) was added Ti (i-OPr) 4 (0.36 mL, 1.21 mmol) dropwise followed by addition of (S)- (-)-2-methyl-2-propanesulfinamide (74 mg, 0.61 mmol). The resulting mixture was stirred for 18h at reflux, cooled to rt, and quenched with brine (2 mL). The mixture was filtered thru a pad of Celite which was washed with EtOAc (2 x 2 mL). The layers were separated and the aqueous layer was extracted with EtOAc (2 x 4 mL). The organic layers were combined, dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude product was purified by preparative TLC (8 x 1000 pM) eluting with CH2CI2/MeOH (20: 1) to afford 0.21 g (80%) of yellow solid. mp 108-110 °C ; M+H = 433.

EXAMPLE 316: Prepared in the same fashion as Example 315 except substituting (R)- (-)- 2-methyl-2-propanesulfinamide to afford 0.25 g (94%) as a yellow solid. mp 107- 109 OC ; M+H = 433.

EXAMPLE 317: (R O_ N N N NH2 "C'lyN- STEP 0 S HN STEP B HN N N N

STEP A: To a solution of sulfinimine (50 mg, 0.12 mmol) from Example 316 in CH2CI2 (2.5 mL) at-40 °C was added MeMgBr (96 mL, 0.29 mmol) dropwise.

The mixture was stirred for 5h at-40 °C and was stirred at rt for 12h. An additional portion of MeMgBr (96 mL, 0.29 mmol) and the mixture was stirred for 12 h. Sat. aq. NH4CI (2 mL) was added and the mixture was extracted with EtOAc (3 x 4 mL). The organic layers were combined, dried (Na2SO4), filtered, and concentrated under reduced pressure to afford 30 mg (58%) of crude residue. This material was taken onto the next step without purification.

STEP B: The crude material from Step A (30 mg, 0.067 mmol) in MeOH (2 mL) was added conc. HCI (2 mL). The mixture was stirred at rt for 12h and the mixture was concentrated to dryness. The crude material was partitioned between CH2CI2 (3 mL) and sat. aq. NaHC03 (2 mL) and the layers were separated. The aqueous layer was extracted with CH2C (2 x 3 mL) and the organic layers were combined. The organic layer was dried (Na2SO4), filtered, and concentrated under reduced pressure to afford 6 mg (24%) of the title compound as a light yellow solid. mp 100-102 °C ; M + H = 345.

EXAMPLE 318:

To a solution of aldehyde (75 mg, 0.23 mmol) from Example 300 in THF/CH2CI2 (5 mL/1 mL) at rt was added MeONHHC) (38 mg, 0.46 mmol) followed by dropwise addition of pyridine (46 lull, 0.57 mmol). The mixture was stirred for 72h at rt whereupon the mixture was concentrated to dryness. The crude material was partitioned between CH2CI2 (3 mL) and sat. aq. NaHC03 (2 mL) and the layers were separated. The aqueous layer was extracted with CH2CI2 (2 x 3 mL) and the organic layers were combined. The organic layer was dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude product was purified by preparative TLC (3 x 1000 pM) eluting with CH2CI2/MeOH (22: 1) to afford 90 mg (100%) of light yellow solid. mp 173-175 °C ; M + H = 359.

EXAMPLE 319: To solution of aldehyde (60 mg, 0.18 mmol) from Example 303 at EtOH (2.5 mL) was added oxindol (48 mg, 0.37 mmol) followed by piperidine (3 drops). The mixture was heated at reflux for 14h and the mixture was cooled to rt. The resultant precipitate was filtered and washed with cold EtOH (2 x 2 mL).

The product was dried under high vacuum to afford 81 mg (100%) of the title compound as an orange/brown solid. mp 182-185 °C ; M+H = 445.

EXAMPLE 320:

To a solution of 3-H analog (106 mg, 0.35 mmol) from Preparative Example 187.10 in AcOH (2 mL) was added 37% aqueous formaldehyde (1.5 ml ; 1.40 mmol) followed by piperidine (100 pL ; 0.37 mmol). The resulting mixture was stirred at rt for 24h and the AcOH was removed under reduced pressure. The mixture was diluted with water (2 mL) and neutralized with 2M NaOH until pH = 8. The aqueous layer was extracted with CH2CI2 (3 x 7 mL) and the organic layers were combined. The organic layer was washed with brine (1 x 4 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure to afford 96 mg (69%) of an off-white solid. mp 88-90 °C ; M+H 399.

EXAMPLES 321-322: By essentially the same procedure set forth in Example 320 only substituting the amines in Column 2 of Table 29 and employing the 3-H adduct from Preparative Example 187.10, the compounds in Column 3 of Table 29 were prepared: TABLE 29 Ex. Column 2 Column 3 CMPD (Amine) (Final Structure) 1. mp (°C) 2. M+H 321 1. mp = 178-180 HN 0 HNtsO 2. M+H = 401 O Nx O w N u Nz HO yin- N/ N-N n w r\ N 1. mp _ 102-104 ho 2. MH = H N6 414 kan EXAMPLE 323:

To a solution of 3-H analog (113 mg, 0.38 mmol) from Preparative Example 187.10 in CH2CI2 (5 mL) at rt was added Aids (215 mg, 1.61 mmol) followed by AcCl (100 mL, 1.40 mmol). The mixture was heated at reflux for 12h and was cooled to rt. The mixture was treated sequentially with 3M HCI (3 mL) followed by sat. aq. NaHC03 (until pH = 8). The layers were separated and the aqueous layer was extracted with CH2CI2 (2 x 5 mL). The organic layers were combined, dried (Na2SO4), filtered, and concentrated under reduced pressure.

The crude product was purified by preparative TLC (8 x 1000 mM) eluting with CH2CI2/MeOH (20: 1) to afford 68 mg (52%) of white solid. mp 220-221 °C ; M+H = 344.

EXAMPLE 324:

Utilizing the method described in Example 323, except employing benzoyl chloride, the title compound was prepared in 61% yield as a white solid. mp 172-175 °C ; M+H = 406.

EXAMPLE 325: To a solution of ketone (100 mg, 0.29 mmol) from Example 323 in CH2CI2 (2.5 mL) at 0 °C was added MeMgBr (0.35 mL, 3. 0M in Et20) dropwise. The resulting mixture was stirred for 18h at rt and was carefully quenched by addition of sat. aq. NH4CI (2 mL) and CH2Cl2 (2 mL) were added. The layers were separated and the aqueous layer was extracted with CH2CI2 (2 x 4 mL). The organic layers were combined, dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude product was purified by preparative TLC (8 x 1000 FM) eluting with CH2CI2/MeOH (10: 1) to afford 68 mg (52%) of a yellow solid. mp 160-162 °C ; M+H = 360.

EXAMPLE 326:

To a solution of ketone (84 mg, 0.24 mmol) from Example 323 in MeOH/THF (1: 1; 2 mL total) at 0 °C was added NaBH4 (12 mg, 0.30 mmol) in one portion. The resulting mixture was stirred for 18h at rt whereupon and additional portion of NaBH4 (12 mg, 0.30 mmol) was added. The mixture was stirred for 12h whereupon the mixture was quenched with ice followed by addition of 1 M NaOH to adjust the pH = 9. The mixture was diluted with CH2CI2 (5 mL). The layers were separated and the aqueous layer was extracted with CH2CI2 (2 x 4 mL). The organic layers were combined, dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude product was purified by preparative TLC (8 x 1000 tM) eluting with CH2CI2/MeOH (10: 1) to afford 25 mg (30%) of a yellow solid. mp 148-150 °C ; M+H = 346.

EXAMPLE 327: Using the same procedure as outlined in Example 326, the ketone (84 mg, 0.21 mmol) was converted to 53 mg (62%) as a light yellow solid. mp 78-80 °C ; M+H = 408.

EXAMPLE 328:

To a solution of 3-H adduct (1.3 g, 4.31 mmol) from Preparative Example 187.10 in CH2CI2 (50 mL) was added Eschenmoser's salt (0.79 g, 4.31 mmol) followed by dropwise addition of TFA (0.56 mL, 7.33 mmol). The mixture was stirred at rt for 48 h and was diluted with CH2CI2 (250 mL). The organic layer was washed with sat. aq. NaHC03 (2 x 125 mL) to afford 1.41 h (92%) of a yellow solid. mp 231-233 °C ; M+H = 359.

EXAMPLE 329: To a solution of tertiary amine adduct (100 mg, 0.28 mmol) from Example 328 in 50% aq. DMF (5 mL) in a pressure tube was added KCN (0.15 g, 2.32 mmol). The tube was capped and heated at 100 °C for 96h. The mixture was cooled to rt and was diluted with EtOAc (25 mL). The organic layer was washed with brine (1 x 5 mL) and water (1 x 5 mL). The organic layers was dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude product was purified by preparative TLC (4 x 1000 jj. M) eiuting with EtOAc to afford 21 mg (30%) of brown solid. mp 152-155 °C ; M+H = 341.

EXAMPLE 330:

To a solution of alcohol (45 mg, 0.14 mmol) from Example 17.10 in CH2CI2 (0.7 mL) at 0 °C was added Et3SiH (26 µL, 0.16 mmol) followed by TFA (25 µL, 0.33 mmol). The mixture was stirred for 2 h at 0 °C and rt for 2 h whereupon additional portions of Et3SiH (26 pL, 0.16 mmol) and TFA (25 µL, 0.33 mmol) were added and the mixture was stirred for 4 h at rt (until complete by TLC). The mixture was concentrated under reduced pressure and the crude residue was partitioned between CH2Cl2 (3 mL) and sat. aq. NaHC03 (1.5 mL).

The layers were separated and the aqueous layer was extracted with CH2CI2 (2 x 4 mL). The organic layers were combined, washed with brine (1 x 5 mL), dried (Na2SO4), filtered and concentrated under reduced pressure. The crude product was purified by prep TLC (4 x 1000 mM) eluting with CH2CI2/MeOH (20: 1) to afford 21 mg (48%) of a yellow solid. mp 146-148 °C ; M+H = 316.

EXAMPLE 331: To a solution of 3-H adduct (90 mg, 0.30 mmol) from Preparative Example 187.10 in conc. H2SO4 (2 mL) at 0 °C was added fuming HNO3 (30 L, 0.72 mmol) dropwise. The resulting mixture was stirred for 1 h at 0 °C whereupon ice

(-1g) was added to the mixture. The resulting precipitate was collected and was washed with water (2 x 2 mL) and CH2CI2 (2 x 2 mL). The crude product was dried under high vacuum to afford 67 mg (60%) of the monosulfate salt as a yellow/orange solid. mp 250 °C ; M+H (free base) = 392.

EXAMPLE 332: Step A:

To a solution of aldehyde (0.10 g, 0.39 mmol) from Preparative Example 168 in THF (2.5 mL) at 0 °C was added CF3TMS (64 mL, 0.43 mmol) followed by CsF (10 mg). The resulting mixture was stirred for 2 h at 0 °C and 2h at rt. 1 M HCI (5 mL) was added and the mixture was diluted with CH2CI2 (10 mL). The layers were separated, the aqueous layer was extracted with CH2CI2 (2 x 10 mL), and the organic layers were combined. The organic layer was washed with brine (1 x 10 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure to afford 127 mg (99%) of a yellow semisolid. M+H =328. The crude product was carried on without further purification.

Step B:

By utilizing the general procedure set forth in Example 1, the 7-CI adduct (127 mg, 0.39 mmol) from Example 332, Step A was reacted with 3- (aminomethyl) pyridine (73 pL, 0.43 mmol) to afford 80 mg (51 %) of the title compound as a light yellow solid. mp 68-72 °C ; M+H = 400.

EXAMPLE 333:

To a solution of aniline (200 mg, 0.69 mmol) from Preparative Example 174 in THF (6 mL) at rt was added aldehyde (114 mg, 0. 83 mmol) from Preparative Example 256 followed by dropwise addition of Ti (i-OPr) 4 (0. 82 mL, 2.77 mmol). The mixture was stirred at reflux for 4 h and was cooled to rt.

NaCNBH3 (347 mg, 5.53 mmol) was added and the mixture was stirred for 2 h at rt. The mixture was cooled to 0 oC, treated with 1 M NaOH (4 mL) and brine (1 mL) and stirred for 30 min. The mixture was extracted with CH2CI2 (3 x 10 mL) and the organic layers were combined. The organic layer was washed with brine (1 x 7 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure.

The crude product was purified by preparative thin-layer chromatography (8 x 1000 uM plates) eluting with CH2CI2/MeOH (25: 1) to afford 89 mg (31 %) of the title compound as a yellow solid. mp 210-213 °C ; M+H = 411.

EXAMPLES 334-337 : By essentially the same procedure set forth in Example 333 only by utilizing the anilines shown in Column 2 of Table 30 and the aldehydes shown in Column 3 of Table 30, the compounds in Column 4 of Table 30 were prepared: TABLE 30 Ex. Column 2 Column 3 Column 4 CMPD (Aniline) (Aldehyde) (Final Structure) 1. mp (°C) 2. M+H 334 B, o H N 1. mp= 85-87 1 N-N 2. M+H = N-N Han 425 H2 NMe2 ru NN NYN NMe2 335 1 Br O9, H 1n1 Br 1. m '160-162 YN_N Nth YN_N 2. M+H = -N NN YN 2. M+H = NH2 HN HN) 451 f NON NON 336 o H i 1. mp _ N 117-119 "N4r 2. 11-1 332 \ NN I N ; N N'N 382 NH2 HN H2 ho I I N. N 337 i o 171-175 [''171-175 F N. N F N'N 2. M+H = At to, N <eNX 271-Mm75H NH2 HN 400 1 N'N EXAMPLE 338: Bu zon N STEP A STEP B HAN NHs H2 NtN I SMe bar Br I Br N NON N-N STEP C N-N HN BocN BocN I f N Y N I NtN NtN N SMe SMe S02Me 0

STEP A : Reaction of aniline (0.20 g, 0.69 mmol) with aldehyde (0.13 g, 0.83 mmol) under the reaction conditions described in Example 333 afforded 70 mg (23%) of thiomethyl derivative as a yellow solid. M+H = 428.

STEP B: To a solution of thiomethyl derivative (60 mg, 0.14 mmol) from Example 338, Step A in dioxane (2 mL) was added Boc20 (61 mg, 0.28 mmol) followed by DMAP (21 mg, 0.17 mmol). The mixture was stirred for 14h at rt and was concentrated under reduced pressure. The crude product was purified by preparative thin-layer chromatography (6 x 1000 pM plates) eluting with hexanes/EtOAc (4: 1) to afford 61 mg (83%) of the title compound as a yellow solid. M+H = 528.

STEP C : To a solution of thiomethyl derivative from Example 338, Step B (41 mg, 0.078 mmol) in CH2CI2 (2 mL) was added MCPBA (33 mg, 0.19 mmol) in one portion. The resulting mixture was stirred for 3h at rt and the mixture was diluted

with CH2CI2 (5 mL) and sat. aq. NaHC03 (2.5 mL). The layers were separated, the aqueous layer was extracted with CH2CI2 (2 x 5 mL), and the organic layers were combined. The organic layer was dried (Na2SO4), filtered, and concentrated under reduced pressure to afford 40 mg (92%) of the sulfone adduct as a light yellow solid. M+H = 560.

STEP D: To a flask charged with sulfone from Example 338, Step C (75 mg, 0.13 mmol) and a stir bar was added morpholine (2 ml ; 22 mmol). The mixture was heated at reflux for 12h, cooled to rt, and concentrated to dryness under high vacuum. The crude product was purified by preparative thin-layer chromatography (6 x 1000 pM plates) eluting with CH2CI2/MeOH (40: 1) to afford 41 mg (68%) of the title compound as a yellow solid. mp 209-210 °C ; M+H = 466.

EXAMPLE 339:

The title compound was prepared according to the procedure outlined in Example 338 except using benzyl amine to afford 12 mg (70%) of a white solid. mp 194-196; M+H = 487.

EXAMPLE 340: Br CI N (N Br i N'l STEP A N_/, BocN STEP B HN 1 NUL N STEP A: To a solution of 5-chloro adduct (0.15 g, 0.34 mmol) in dioxane/DIPEA (2. 5mL/1. OmL) at rt was added cyclopentylamine (0.041 pL, 0.41 mmol) dropwise. The resulting solution was stirred at reflux for 16h, cooled to rt, and concentrated under reduced pressure. The crude material was purified by preparative thin-layer chromatography (8 x 1000 µM) eluting with CH2CI2/MeOH (25: 1) to afford 148 mg (89%) of a yellow oil. M+H = 489.

STEP B: Removal of the t-butoxycarbonyl protecting group with TFA To a solution of the compound prepared in Example 340, Step A (135 mg, 0.28 mmol) in CH2CI2 (2 mL) at rt was added TFA (0.54 mL, 7.0 mmol) dropwise.

The resulting solution was stirred for 18 h at rt and was concentrated under reduced pressure. The crude material was redissolved in CH2Cl2 (5 mL) and the organic layer was sequentially washed with sat. aq. NaHC03 (2 x 2 mL) and brine (1 x 2 mL). The organic layer was dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude material was purified by preparative thin- layer chromatography (8 x 1000 pM) eluting with CH2CI2/MeOH (20: 1) to afford 105 mg (97%) of white solid. mp 120-122 °C ; M+H = 389.

EXAMPLE 341: HOu Br H Br CI N\ (,,, N N\ ( CluHNsA Ns§NoA I I N N o, E n Step A:

By essentially the same procedure set forth in Example 340 only substituting the appropriate amine, the above compound was prepared. MS: MH+= 431.

Step B: Removal to t-butoxycarbonyl protecting group with KOH.

To a mixture of the compound prepared in Example 341, Step A (0.14 g, 0.26 mmol) in EtOH : H20 (3 mL, 2: 1) was added KOH (0.29 g, 20 eq. ) in one portion. The resulting solution was stirred at reflux 14 hours, cooled to room temperature, and concentrated under reduced pressure. The residue was taken up in CH2CI2 (5 mL) and diluted with saturated NaHC03 (2 mL). The layers were separated and the aqueous layer extracted with CH2CI2 (2 x 4 mL). The combined organics were washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by preparative TLC (8 x 1000 M) eluting with 5% MeOH in CH2CI2 solution (0.066 g, 59% yield). MS: MH+ = 432; mp = 219-221°C.

EXAMPLES 342-397: By essentially the same procedure set forth in Example 340 only substituting the chlorides in Column 2 of Table 31 and removing the t- butoxycarbonyl protecting group by the method shown in Column 3 of Table 31, the compounds shown in Column 4 of Table 31 were prepared.

Table 31 Ex. Column 2 Column Column 4 CMPD 3 342 HCI/n Br MS : MH+ = 403 HOs H HN m. p. 151-157 °C N H OH N-N HN if N 343 N HCI MS : MH+ = 466 WNXNCNH CN Ne m. p. 212-217 °C Bu NH N NH N- ; N XN_N HN N I I N gr MS : MHT = 405 "iNH2 m. p. 53-58 °C OH OH N-N HN N N 345 HCI H Br MS : MH+ = 405 NH2 NyN m. p. 63-69 OC OH OH N HN kan N 346 HO~NH2 HCI HO~N NoA MS : MH+-363 346 ho W Nz N HN N N HCI MS : Mu+-407 Br m. p. 148-151 °C V HA _N ICI N 348 HCI MS : MHt = 435 HO HO m. p. 56-59 °C Bu NH N N ( Ho. HN HA HN /II N 349 HCI MS : MH+ = 445 m. p. 66-68 °C Br _, NH Ho-,'NyN HA I N 350 KOH MS : MH+ = 417 NH N N Br m. p. 149-151 °C HO HO N HN N 351 KOH Br MS : MH+ = 431 NH M'P'111-114 OC JO HO N OH HN N I I N 352rV KOH7BT MS : MH'=417 H3C0 N N N m. p. 53-58 OC H H3CO N HN HAN. kan N 353 KOH Br MS : MH =456 i : NTN m. p. 186-189 °C H CN NN H N CON-N 354 KOH Br MS : MH+ 416 O H2N\\o XN_N 2 OI H H2N0 HN 'OH ° »"oLN-N han N ,. N N \ 68-70 -c. - HN. kan HN N I I HN N gr 1. m = 181-183 NH KOH N N 2. MpH = 404 'OH Nz OH HN I I N 357 Br NH2 TFA N N 1. mp- ""ou 69-71 Ho. kan N N 358 . NH Br 1. mp = 182-184 o, NH2 KOH, N NsA 2 M+H-404 OH 04N_N HN OH HN N 359 NH2 KOH HO H Br N N 1. mp = 202-204 \J YN-N 2. M+H = 418 Oh HAN HN N N NH gr aNyN 1. mp = 160-162 2. M+H = 402 fuzz HAN HN I I \ N Br 361 NH TFA N N 1. mp = 151-153 2. M+H = 416 cr N-N/ HN N 362 NH2 KOH H Br 1. mp 140 2. M+H = 418 OU. N ON HAN I I N yv 363 NH2 KOH H Br 1. mu = 139-142 2. M+H = 418 OH NN OU HN N N 364 NH2 KOH H Br NH2 KOH N N 1. mp = 115-117 2. M+H = 418 OH a w NN HO. un HN N 366 H2No TFA H2N0 1. mu = 102-104 ., \NH 2. M+H = 445 . won HN /I N (+/-) HN 1. mp = 118-120 o NH2 otNy>Nt 2 M+H = 474 U U . N (+/-) HN HN N N 368 Eto o TFA Eto 0 1. mu = 106-108 ,, NH2,, N N\ (2. M+H = 474 ,, \Ny (+/-) HN N-N han 1. mp = 160-161 NH N N 2, NI+H = 464 C Y / N N HN N N 370 OH TFA OH H Br 1. mp NH2 N N 93-95 r i 2. M+H = 432 HAN N N nu bu 371 NH2 KOH H Br 1. mp = 108-110 2. M+H = 432 N OHHN. OH HN N I I N NH Br 1. mp = 180-182 2. M+H = 418 Ho HAN. HAN HAN I I N 373 NH TFA H Br As N : TN,, N 1. mp = 169-170 Boche M+H = 417 BOCHE NN HO HN /1 I I N 374 NH2 TFA H Br N 77-79 N < J L. A Bn N joN~N 2. M+H = 479 Bn Y HN N I I N 375/NH2 TFA H. Br 375 NH Br 375 2 TFA, , N N 1. mp = 76-79 2. M+H = 479 BNn <NJ iN-N/2 2. M+H = 479 Bn N"""N Bn HN kan N Br (W/gNyzNsA 1. mp = 105-107 2. M+H 389 Boc NH 9aN-N H HN HN N N 377/ < j. ssNsv, NoA 1, mp = 105-107 2. M+H = 389 Boc No N H T HN N I I N ,,, NHBoc C H2N\oN N 1 1. mp = 130-133 2. M+H = 389 N N'N HAN han I I N 379 NHAc TFA Br ACHN N 1. mp 132-135 2. M+H = 431 H N- N HAN I I N 380 TFA Br 1. mp = 135-137 2. MHz YN-N 372 HN kan N 381 j KOH Br NH N N j 1. mp = 78-82 2. M+H = 432 /, OH/, OH \ NN HN N 382 TFA Br VNH Y-N., N. J' 1. mp= 101-103 2. M+H = 432 0 0 OMe OMe HN RUZ ZON 383 TFA Br 1. mp 92-95 NH _s 2 M+H = 472 N N 0 0 O-=1 1 W N N OMe OMe HN N 384 tua N 3$4 TFA 1. mp = 107-111 2. M+H 444 OH ON OH OH Y" HN N N 384. TFA Br 1. mp N 1'\ 2. M+H = 417 HO HAN HA kan I I N NH Br 384-HO N,, IN) _ 1. mp = 210-212 2. M+H = 391 Won N HN N 385 TFA 1. mp = 122-124 gr 2. M+H = 403 NH N N NON HN kan N 386 CN TFA CN 1. mp = 186-188 2. M+H 491 Bu YN HN. N HN TN-N HAN N 387 0 TFA ° O 1. mp = 173-175 N Br 2. M+H 483 xi HAN HN N 388 v NH TFA N H Br 1. mp=167-169 N 2. M+H = 450 NON H HAN. HN ICI N , , NH Br N 1. mp = 90-92 2. M+H = 374 W NN HN N 390 TFA H Br Br /'H2/NN 1. mp= 113-115 2. M+H 404 \ non HN ZON N N 391 NH TFA N N Br 1. mp = 114-116 2. M+H = 404 N HN N N 392 TFA Br LCMS : MH+ 347 ; Me2N>, N4 WN_N/2 HNMe2 HN N N 393 TEA Br LCMS : MH+= 333 ; MeHN.. N/ NON H2NMe HN N I I N 394 TFA N N Br LCMS : MH+= 359 ; W N, N NH2 HN N N N 395 TFA H Br LCMS : MH=405 ; N N \ ( HO N'N NHs HN ZON N 396 TFA H Br LCMS : MH =405 ; N N \ _ Nu W non HO HA N 397 TFA H Br LCMS : MH = 391 ; N yN-_r N un HO HO ZON

Additional data for select example shown below : Example 392 : 1H NMR (DMSO-d6) 5 8.65 (s, 1 H), 8.46 (d, J = 3.3 Hz, 1 H), 8.21 (t, J = 6.6 Hz, 1H), 7.90 (s, 1H), 7.80 (d, J = 7.8 Hz, 1H), 7.35 (dd, J = 7.8, 4.8 Hz, 1H), 5.46 (s, 1 H), 4.61 (d, J = 6.9 Hz, 2H), 3.01 (s, 6H).

Example 393 : 1H NMR (CDC13) 5 8.65 (s, 1H), 8.60 (d, J = 4.8 Hz, 1H), 7.76 (s, 1H), 7.70 (m, 1H), 7.32 (dd, J = 8. 1,4. 8 Hz, 1H), 6.43 (t, J = 6.0 Hz, 1H), 5.08 (s, 1H), 4.80 (m, 1H), 4.56 (d, J = 6. 0 Hz, 2H), 2.96 (d, J = 5. 1 Hz, 3H).

Example 394 : 1H NMR (CDC13) # 8. 68 (s, 1 H), 8.60 (d, J = 4.8 Hz, 1 H), 7.76 (s, 1H), 7.72 (m, 1H), 7.32 (dd, J = 7.8, 5.4 Hz, 1 H), 6.55 (t, J = 5.7 Hz, 1 H), 5.53 (s, 1 H), 5.35 (s, 1 H), 4.62 (d, J = 5.7 Hz, 2H), 2.49 (m, 1 H), 0.75 (m, 2H), 0.51 (m, 2H).

Example 395 :'H NMR (CDCl3) 8 8.65 (s, 1 H), 8.60 (d, J = 4. 0 Hz, 1 H), 7.75 (s, 1H), 7.69 (m, 1H), 7.33 (dd, J = 8.1, 5.1 Hz, 1H), 6.45 (t, J = 6. 0 Hz, 1H), 5.07 (s, 1H), 4.69 (m, 1H), 4.54 (d, J = 6.0 Hz, 2H), 3.98 (m, 1H), 3.79 (dd, J = 10. 8,2. 4 Hz, 1H), 3.59 (dd, J = 11. 1,7. 2 Hz, 1 H), 1.59-1. 36 (m, 4H), 0.94 (t, J = 6.9 Hz, 3H).

Example 396 : 1H NMR (CDCl3) b 8.60 (s, 1 H), 8.56 (d, J = 4.2 Hz, 1 H), 7.73 (s, 1H), 7.66 (m, 1H), 7.31 (dd, J = 7. 8,4. 8 Hz, 1H), 6.51 (t, J = 6.0 Hz, 1H), 5.05 (s, 1H), 4.86 (d, J = 6.6 Hz, 1H), 4.50 (d, J = 6. 0 Hz, 2H), 3.94 (m, 1H), 3.78 (dd, J = 11.1, 2. 4 Hz, 1H), 3.57 (dd, J = 11. 1,7. 2 Hz, 1H), 1.57-1. 34 (m, 4H), 0.91 (t, J = 7.2 Hz, 3H).

Example 397 : 1H NMR (CDCI3) # 8.65 (s, 1H), 8. 59 (d, J = 4.5 Hz, 1H), 7.75 (s, 1H), 7.69 (m, 1H), 7.31 (m, 1H), 6.43 (t, J = 6.0 Hz, 1H), 5.06 (s, 1H), 4.88 (m, 1 H), 4.55 (d, J = 6.0 Hz, 2H), 3.70 (m, 2H), 3.38 (m, 2H), 1.79-1. 61 (m, 4H).

EXAMPLES 398-416 : By essentially the same conditions set forth in Example 341, Steps A and B only substituting the compound prepared in Preparative Example 193.10, the compounds in Column 4 of Table 32 were prepared.

Table 32 Ex. Column 2 Column Column 4 CMPD 3 398 Br MS : MH+ = 419 H0/\N NJ m. p. 102-105°C N HAN. HAN N, o- 399 H Br MS : MH+ = 421 HO NH2 OH44 HO NEZ OH \ NN HN Nz Nz 400r/HBrMS : MH"=421 --CN N m. p. 78-79 OC OH OH N-N HN /ici+ Nz 401 MS : MHT = 433 NH N N Br m. p. 228-231 °C HO HO XN_N HN r\ if+ 402 Br MS : MH+ = 447 NH AH N e m. p. 97-102 °C NON OH OH HN /ici+ N_ 403 H Br MS : Mu-'= 421 N N M. P. oc HO NH2 OH N-N HN + Nez 404 H Br MS : MH+ = 421 s N N m. p. °C HO \ NH2 OH SN-N HN N o- 405 Br MS : MH = 386 405 NH NAwNTA m. p. °C NU HAN zur HAN nez 407 NH2 KOH H Br N yN 1. mp = 98-100 2. M+H = 390 HAN HO /ici+ Nz 408 TFA NH2 H Br 1. mp = 170-173 a X N Ct 2. M+H = 404 NN N HN 0- . bar 1, NH2 KOH I., N N 1. mp = 219-221 2. M+H = 420 HN ON Han zu Nez 410 hou .., NNH2 2. M+H = 448 O NN ON+so Nz 411 TFA Br NH N N\ (1. mp = 81-83 2. M+H 448 COH COH4N-N HN Nz N, o- 412/ TFA/ Br NH N N . ( 1. mp = 136-138 2. M+H = 448 N OMe OMe N HAN Han. 6 413 NaOMe KOH Br N,, T 1. mp = 107-110 2. M+H=351 N-N HN I + lui 414 vzN4 LCMS : MH+= 375 ; w N N NH2 HN n N-k, 0-

Additional data for select examples shown below : Example 414 : 1H NMR (DMSO-d6) 8 8. 26 (s, 1H), 8.23 (m, 1H), 8.13 (m, 1H), 7.90 (s, 1 H), 7.40-7. 27 (m, 3H), 5.34 (s, 1 H), 4.49 (d, J = 6.3 Hz, 2H), 2.56 (m, 1 H), 0.67 (m, 2H), 0.35 (m, 2H).

Example 403 :'H NMR (DMSO-de+CDOs) # 8.08 (s, 1 H), 7.90 (d, J = 6.3 Hz, 1H), 7.49 (s, 1H), 7.34 (t, J = 6.3 Hz, 1H), 7.16-7. 09 (m, 2H), 5.65 (d, J = 6. 6 Hz, 1 H), 4.97 (s, 1 H), 4.90 (s, 1 H), 4.29 (d, J = 6.3 Hz, 2H), 3.70 (m, 1 H), 3. 46 (m, 1H), 3.34 (m, 1H), 1.35-1. 17 (m, 4H), 0.71 (t, J = 7.2 Hz, 3H).

Example 404 : 1H NMR (DMSO-d6) # 8.21 (s, 1H), 8.12 (d, J = 6.6 Hz, 1H), 8.06 (m, 1H), 7.86 (s, 1H), 7.38 (t, J = 7. 8 Hz, 1H), 7.30 (d, J = 7.5 Hz, 1H), 6.73 (d, J = 8.7 Hz, 1H), 5.28 (s, 1H), 4.70 (t, J = 5.1 Hz, 1H), 4.41 (d, J = 6.6 Hz, 2H), 4.00 (s, 1H), 3.39 (m, 1 H), 1.53 (m, 1 H), 1.36-1. 25 (m, 3H), 0.86 (t, J = 7. 0 Hz, 3H).

EXAMPLES 417-421 : By the procedure set forth in Chem. Pharm. Bull. 1999,47, 928-938. utilizing the oxygen or sulfur nucleophiles shown in Column 2 as described of Table 33 and by employing the cleavage method listed in Column 3 of Table 33, the compounds in Column 4 of Table 33 were prepared: TABLE 33 Ex. Column 2 Column 3 Column 4 CMPD (Nucleophile) (Cleavage (Final Structure) 1. mp. method) 2. M+H 417 NaSMe TFA Br 1. mp = 172 2. M+H = 351 W NON HO It N 418 NaSt-Bu TFA Br ,) N NS) (1. mp = 165-168 \ iN_N/> 2. M+H = 392 W NON N HN I I 419 NaSPh TFA Br 1. mp 154 2. M+H = 492 nez HN N I I N 420 NaOMe TFA 1. mp = 161-163 2. M+H = 335 bu oye r F 1 Br HAN HN HAN I 421 NaOPh TFA Br 1 1. mp = 64-66 W 2. M+H = 397 \ nez HN HAN ICI N EXAMPLE 422:

To a solution of amino compound (18 mg, 0.043 mmoi) from Example 373 in CH2CI2 (1 mL) at rt was added DIPEA (10 pL, 0.056 mmol) followed by MeS02CI (4 mL, 0.052 mmol). The mixture was stirred at rt for 12 h and was diluted with CH2CI2 (2 mL) and sat. aq. NaHC03 (2 mL). The layers were separated and the organic layer was extracted with brine (1 x 2 mL). The organic layer was dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude material was purified by preparative thin-layer chromatography (4 x 1000 pM) eluting with CH2CI2/MeOH (20: 1) to afford 16 mg (75%) of white solid. mp 152-154 °C ; M+H = 495.

EXAMPLES 423-424:

Utilizing the procedure outlined in Example 422, the amino compounds (Column 2) were converted to the corresponding methylsulfonamides (Column 3) in Table 34.

TABLE 34 Ex. Column 2 Column 3 CMPD (Amine) (Final Structure) 1. mp. 2. M+H 423 H Br H Br 1. mp = 166- N N \ (N N (168 T : 2. M+H 467 J N N \N N N N HAN HN) °-S N N wN %, N . N kN 424HBF*HBT' 424 N N/, N N 1. mp = 165- 168 N N_N N % gN-N 2. M+H = H HN °-S I 467 H o 467 Nz

EXAMPLE 425: STEP A: A mixture of the compound prepared in Preparative Example 194 (132 mg, 0.25 mmol), tributylvinyltin (95 mg, 0.30 mmol) and

tetrakis (triphenylphospine) palladium (29 mg, 0.025 mmol) in anhydrous dioxane (5 mL) was refluxed under N2 for 24 hr. The solvent was evaporated and the residue was purified by flash chromatography using 2: 1 CH2CI2 : EtOAc as eluent to yield yellow waxy solid (53 mg, 50%). LCMS: MH+=428.

STEP B:

A mixture of the compound prepared in Example 425, Step A (50 mg, 0.12 mmol) and KOH (100 mg, 1.80 mmol) in ethanol (3 mL) and H20 (0.6 mL) was stirred at 70°C under N2 for 24 hr. NaHC03 (1.0 g), Na2SO4 (2. 0g), and CH2CI2 (20 mL) were added, the mixture was shaken and then filtered. The solvent was evaporated and the residue was purified by flash chromatography using 20: 1: 0.1 CH2CI2 : MeOH: conc. NH40H as eluent to yield yellow waxy solid (17 mg, 45%). LCMS: MH+=328. Mp=48-51 °C.

EXAMPLE 426: STEP A:

By essentially the same procedure set forth in Example 425, Step A only using tributylmethylethynyltin, the compound shown above was prepared.

STEP B :

A mixture of the compound prepared in Example 426, Step A (150 mg, 0.34 mmol) and Pt02 (30 mg, 0.13 mmol) in glacial acetic acid (5 mL) was stirred under 1 atmosphere of H2 for 20 hr. The mixture was filtered, fresh Pt02 (30 mg, 0.13 mmol) was added and the mixture was stirred under 1 atmosphere of H2 for 2.5 hr. The mixture was poured onto Na2CO3 (20 g) and H20 (200 mL) and it was extracted with CH2CI2 (4x20 mL). The combined extracts were dried over Na2SO4 and filtered. The solvent was evaporated and the residue was purified by flash chromatography using 1: 1 CH2CI2 : EtOAc as eluent to yield yellow waxy solid (68 mg, 45%).

STEP C:

By essentially the same procedure set forth in Example 425, Step B only substituting the compound prepared in Example 426, Step B, the compound shown above was prepared, MS: MH+=344. Mp=110-112 °C.

EXAMPLE 427: STEP A:

A mixture of the compound prepared in Preparative Example 194 (527 mg, 1.00 mmol), triethyl (trifluoromethyl) silane (666 mg, 3.60 mmol), potassium fluoride (210 mg, 3.60 mmol), and Cul (850 mg, 4.46 mmol) in anhydrous DMF (4 mL) was stirred in a closed pressure vessel at 80°C for 72 hr. CH2C12 (80 mL) was added and the mixture was filtered through Celite. The solvent was evaporated and the residue was purified by flash chromatography using 2: 1 CH2CI2 : EtOAc as eluent to yield pale orange waxy solid (70 mg, 15%). LCMS: M+=470.

STEP B: TFA (0.70 mL) was added at 0°C under N2 to a stirred solution of the compound prepared in Example 427, Step A (70 mg, 0.15 mmol), in anhydrous CH2CI2 (3 mL). The mixture was stirred at 0°C for 10 min, then at 25°C for 2 hr. It was poured into 10 % aqueous Na2CO3 (50 mL), extracted with CH2CI2 (3x15 mL), dried over Na2SO4, and filtered. The solvent was evaporated and the residue was purified by flash chromatography using EtOAc as eluent to yield off- white solid (40 mg, 73%). LCMS: M+=370. Mp=156-158 °C.

EXAMPLE 428: STEP A:

A mixture of the compound prepared in Preparative Example 193 (100 mg, 0.28 mmol), tetracyclopropylltin (91 mg, 0.32 mmol), Pd2dba3, (8.0 mg, 0.009 mmol) and Pd (Pt-Bu3) 2 (9. 0 mg, 0.017 mmol) in anhydrous dioxane (3 mL) was refluxed under N2 for 27 hr. The solvent was evaporated and the residue was purified by flash chromatography using 1: 1 CH2CI2 : EtOAc as eluent to yield colorless waxy solid (38 mg, 38%). LCMS: MH+=366.

STEP B:

A mixture of the compound prepared in Example 428, Step A (36 mg, 0.10 mmol) and KOH (300 mg, 5.40 mmol) in ethanol (3 mL), 1,2- dimethoxyethane (3.0 mLO and H20 (0.8 mL) was refluxed under N2 for 4 hr. It was poured into saturated aqueous NaHC03 (100 mL), extracted with CH2CI2 (5x10 mL), dried over Na2SO4, and filtered. The solvent was evaporated and the residue was purified by flash chromatography using 30: 1 EtOAc: MeOH as eluent to yield colorless waxy (18 mg, 69%). LCMS: MH+=266.

STEP C:

N-bromosuccinimide (12 mg, 0.068 mmol) in anhydrous CH3CN (2 mL) was added under N2 to a stirred solution of the compound prepared in Example 428, Step B (18 mg, 0.068 mmol), in anhydrous CH3CN (2 mL). The mixture was stirred at 25°C for 2 hr. The solvent was evaporated and the residue was purified by flash chromatography using EtOAc as eluent to yield 5 mg (17%) of the dibromo compound (white solid, LCMS: MH+=370, mp= 150-152°C) and 8 mg (34%) of the monobromo compound (colorless solid, LCMS: M+=344, mp= 196-198°C).

EXAMPLE 429: STEP A: 1, 3-propanesultam (72 mg, 0.60 mmol) in anhydrous DMF (3 mL) was added under N2 to 60 % NaH in mineral oil (36 mg, 0.90 mmol). The mixture was stirred for 20 min, then the compound prepared in Preparative Example 196 (200 mg, 0.46 mmol) was added. The mixture was stirred at 100°C for 30 min, the solvent was evaporated and the residue was purified by flash chromatography using EtOAc as eluent to yield colorless solid (150 mg, 63%).

LCMS: M+=523.

STEP B:

TFA (1.5 mL) was added at 0°C under N2 to a stirred solution of the compound prepared in Preparative Example 196 (140 mg, 0.27 mmol), in anhydrous CH2CI2 (5 m, L). The mixture was stirred at 0°C for 10 min, then at 25°C for 2 hr. It was poured onto Na2CO3 (10 g), extracted with CH2CI2 (3x50 mL), and filtered. The solvent was evaporated and the residue was purified by flash chromatography using 40: 1 EtOAc: MeOH as eluent to yield white solid (32 mg, 28%). LCMS: M+=423. Mp=218-220°C.

EXAMPLE 430: Where: R2=H, or Cl 3-Bromo-7-chloro-5- (2-chlorophenyl) pyrazolo [1,5-a] pyrimidine (1 equivalent) (prepared as described in Preparative Example 129), or 3-Bromo-7- chloro-5-phenylpyrazolo [1,5-a] pyrimidine (1 equivalent) (prepared as described in Preparative Example 127), R1NH2 (1.2 equivalents) and diisopropyl ethylamin (2 equivalents) were dissolved in anhydrous 1,4-dioxane and the mixture was heated at 75°C for the time given in Table 97. The solution was evaporated to dryness and the residue was chromatographed on a silica gel column as described in Table 97, to give the title compound.

Using the appropriate reactants and essentially the same procedure as described above, the products of Examples 431 to 438 were prepared. Variations in the reaction conditions are noted in Table 35.

TABLE TABLE 35 FABMS Reaction Chromatographic MH ConditionsData Br n 15x2. 5cm - C J'0. 5-2% (10% Cone. 0. 0. 5-2% (10% Conc. 431 HN 463. 8 463. 0 750C 52% ammonium 26h hydroxide in í8 methanol)- dichloromethane 0 Br 1 5x5cm Dichloromethane ; N N ? 26h 1. 5% (10% Conc. 432 HN 429. 3 429. 2 . 53% ammonium 1 5 hydroxide in tNyNH2 39h methanol)- dichloromethane 0 15x5cm Dichloromethane ; N-N-rCl'3. 5-15% (10% 433 HN 477. 8 477. 1 26h 48% Conc. ammonium 1, hydroxide in methanol)- dichloromethane 15cm Dichloromethane ; N_N ? Cl 75 C/3. 5-15% (10% 434 un 477. 8 477. 0 750C 50% Conc. ammonium hydroxide in y methanol)- o dichloromethane Br 1n1 15x2. 5cm 75°C/ 3% (10% Conc. 24h ammonium 435 HN 434. 8 434. 1 250C 53% hydroxide in ethanol)- 65h dichloromethane w CH3 15x2. 5cm 3% (10% Conc. 436 434. 8 434. 2 750C 31% ammonium 27h hydroxide in methanol)- dichloromethane Br Y -N a HN t4 CH, Br 15x2. 5cm 750C 0. 25% (10% Conc. 21 h ammonium 437 HN 97% 25°C hydroxide in 46h methanol)- dichloromethane 75°C/ f) 750C 60x2. 5cm 438 438. 7 438. 1-20°C/95% hexane 72h hexane ici T ! ! N

Additional physical data for the compounds are given below : EXAMPLE 431: Reactants: 3-Bromo-7-chloro-5-(2-chlorophenyl)pyrazolo [1,5- a]pyrimidine (110mg, 0. 318mmoles) (prepared as described in Preparative Example 129); 3-(aminomethyl)piperidine-1-carboxamide (60mg, 0. 382mmoles) (prepared as described in Preparative Example 241 above); diisopropyl ethylamin (0. 111mL, 0. 636mmoles) ; anhydrous 1,4-dioxane (2.5mL). Physical properties: HRFABMS: m/z 463. 0628 (MH+). Calcd. for C19H21N60BrCI : m/z 463.0649 : 5H (CDCI3) 1.38 (1H, m, CH2), 1.52 (1H, m, CH2), 1.73 (1H, m, CH), 1.93 (1 H, m, CH2), 2.02 (1 H, m, CH2), 2.98 (1 H, m, CH2), 3.06 (1 H, m, CH2), 3.37 (2H, m, CH2), 3.58 (1 H, m, CH2), 3.82 (1 H, m, CH2), 4.87 (2H, bm, CONH2), 6.28 (1 H, s, H6), 7.02 (1 H, m, NH), 7.36 (2H, m, Ar-H), 7.45 (1 H, m, Ar-H), 7.68 (1 H, m, Ar-H) and 8.00 ppm (1 H, s, H2); 8c (CDCl3) CH2: 23.7, 28.1, 44.6, 45.5, 47.2 ; CH: 35.2, 87.4, 127.2, 130.1, 130.3, 131.6, 143.9 : C: 83.1, 132.1, 138.6, 145.5, 146.5, 158.0, 158.4.

EXAMPLE 432: Reactants: 3-Bromo-7-chloro-5-phenylpyrazolo [1,5-a] pyrimidine (500mg, 1. 62mmoles) (prepared as described in Preparative Example 127); 3- (aminomethyl) piperidine-1-carboxamide (306mg, 1. 944mmoles) (prepared as described in Preparative Example 241 above); diisopropyl ethylamin (0.566mL, 3. 24mmoles) ; anhydrous 1,4-dioxane (13mL). Physical properties: HRFABMS: m/z 429.1031 (MH+). Calcd. for C19H22N60Br : m/z 429.1038 ; 8H (CDCl3) 1.44 (1H, m, CH2), 1.59 (1 H, m, CH2), 1.79 (1H, m, CH), 2.01 (1H, m, CH2), 2. 08 (1 H, m, CH2), 3.03 (1H, m, CH2), 3.13 (1H, m, CH2), 3.39 (1H, m, CH2), 3.47 (1H, m, CH2), 3.63 (1 H, m, CH2), 3.90 (1 H, m, CH2), 4.88 (2H, bm, CONH2), 6.40 (1 H, s, H6), 6.90 (1H, m, NH), 7.53 (2H, m, Ar-H), 8. 02 (1H, s, H2) and 8.12 (1H, m, Ar- H); 8c (CDC13) CH2: 23.7, 28. 2,44. 7,45. 5,47. 3; CH: 35.2, 82.9, 127.5, 127.5, 128.7, 128.7, 130.0, 143.9 ; C: 83.0, 138.5, 145.8, 147.1, 158.3, 158. 5.

EXAMPLE 433: Reactants: 3-Bromo-7-chloro-5- (2-chlorophenyl) pyrazolo [1,5- a] pyrimidine (347mg, 1. 01mmoles) (prepared as described in Preparative Example 129); 3-(aminoethyl) piperidine-1-carboxamide (208mg, 1. 21mmoles) (prepared as described in Preparative Example 242 above); diisopropyl ethylamin (0.393mL, 2. 02mmoles) ; anhydrous 1,4-dioxane (9mL). Physical properties: 8n (CDCl3) 1.24 (1 H, m, C. H2), 1.55 (1 H, m, CH), 1.72 (4H, m, CH2), 1.93 (1 H, m, CH2), 2.69 (1 H, m, CH2), 2.94 (1 H, m, CH2), 3.55 (2H, m, CH2), 3.73 (1 H, m, CH2), 3. 98 (1 H, m, CH2), 4.83 (2H, bm, CONH2), 6.55 (1 H, s, H6), 6. 78 (1 H, m, NH), 7.41 (2H, m, Ar-H), 7.50 (1 H, m, Ar-H), 7.75 (1 H, m, Ar-H) and 8.04 ppm (1 H, s, H2); 8c (CDC13) CH2: 24.6, 30.7, 32.6, 39.9, 45.3, 49.3 ; CH: 33.3, 87.5, 127.4, 130.1, 130.2, 131.6, 143. 8 ; C: 83. 2,132. 1,138. 8,145. 7, 146.2, 158.1, 158.1.

EXAMPLE 434: Reactants: 3-Bromo-7-chloro-5- (2-chlorophenyl) pyrazolo [1,5- a] pyrimidine (275mg, 0. 803mmoles) (prepared as described in Preparative Example 129); 4-(aminoethyl)piperidine-1-carboxamide (165mg, 0. 963rmmoles) (prepared as described in Preparative Example 243 above); diisopropyl ethylamin (0. 311 mL, 0. 963mmoles) ; anhydrous 1,4-dioxane (7.2mL). Physical properties: 8H (d6-DMSO) 1.00 (2H, m, CH2), 1.50 (1 H, m, CH), 1.59 (2H, m,

CH2), 1.67 (2H, m, CH2), 2.60 (2H, m, CH2), 3.48 (2H, m, CH2), 3.70 (2H, m, CH2), 5.84 (2H, bs, CONH2), 6.43 (1 H, s, H6), 7.50 (2H, m, Ar-H), 7.62 (2H, m, Ar-H), 8.30 (1 H, s, H2) and 8.36 ppm (1 H, m, NH); 8c (d6-DMSO) CH2: 31.5, 31.5, 34.8, 43.5, 43.5, 43.5 ; CH: 32.8, 86. 8,127. 1,129. 7, 130.3, 131.0, 143.3 ; CH: 81.3, 131.0, 138.7, 145.1, 146.4, 157.3, 157.8.

EXAMPLE 435: Reactants: 3-Bromo-7-chloro-5-phenylpyrazolo [1,5-a] pyrimidine (174mg, 0. 507mmoles) (prepared as described in Preparative Example 129) and 3-(aminomethyl)-1-methylpiperidine (65mg, 0. 507mmoles) (prepared as described in Preparative Example 244 above); diisopropyl ethylamin (0.178mL, 1. 014mmoles) ; anhydrous 1,4-dioxane (2.5mL). Physical properties: HRFABMS: m/z 434.0742 (MH+). Calcd. for C19H22N5BrCI : m/z 434.0747 ; 8H (CDCI3) 1.18 (1 H, m, CH2), 1. 68 (1 H, m, CH2), 1. 80 (1 H, m, CH2), 1.87 (1 H, m, CH2), 1.96 (1H, m, CH), 2.14 (2H, m, CH2), 2.32 (3H, s, NCH3), 2.75 (1H, m, CH2), 2.29 (1H, m, CH2), 3.42 (2H, m,-NHCH2CH), 6.36 (1 H, s, H6), 6.64 (1 H, bm, NH), 7.41 (2H, m, Ar-H), 7.51 (1 H, m, Ar-H), 7.74 (1H, m, Ar-H) and 8.06 ppm (1 H, s, H2); 8c (CDC13) CH3 : 46.6 ; CH2: 24.4, 27.9, 46.1, 56.1, 59.6 ; CH : 36.0, 87.4, 127.1, 130.1, 130.2, 131.6, 143.8 ; C: 83.2, 132.1, 138.9, 145.6, 146.4, 158.2.

EXAMPLE 436: Reactants: 3-Bromo-7-chloro-5-phenylpyrazolo [1,5-a] pyrimidine (111. 4mg, 0. 325mmoles) (prepared as described in Preparative Example 129); 4-(aminomethyl)-1-methylpiperidine (50mg, 0. 39mmoles) (prepared as described in Preparative Example 245 above); diisopropyl ethylamin (0. 1135mL, 0. 65mmoles) ; anhydrous 1,4-dioxane (1.5mL). Physical data: HRFABMS: m/z 434.0735 (MH+). Calcd. for C19H22N5BrCI : m/z 434.0747 ; 8H (CDC13) 1.42 (2H, m, CH2), 1.72 (1 H, m, CH), 1.82 (2H, m, CH2), 1.93 (2H, m, CH2), 2.20 (3H, s, NCH3), 2.89 (2H, m, CH2), 3.34 (2H, m,-NHCH2CH), 6.31 (1H, s, H6), 6.46 (1 H, m, NH), 7.36 (2H, m, Ar-H), 7.46 (1 H, m, Ar-H), 7.70 (1 H, m, Ar-H) and 8.00 ppm (1 H, s, H2); 8c (CDC13) CH3 : 46.4 ; CH2: 30.2, 30.2, 48.0, 55.3, 55.3 ; CH: 35.4, 87.5, 127.2, 130.2, 130.2, 131.6, 143. 8 ; C: 83.3, 132.2, 138.9, 145.7, 146.4, 158.1.

EXAMPLE 437: Reactants: 3-Bromo-7-chloro-5-phenylpyrazolo [1, 5-a] pyrimidine (191mg, 0. 557mmoles) (prepared as described in Preparative Example 129); 3- (aminomethyl) benzonitrile (88.3mg, 0. 668mmoles) (prepared as described in Preparative Example 246 above); diisopropyl ethylamine (0. 192mL, 1. 114mmoles) ; anhydrous 1,4-dioxane (4.5mL). Physical data: HRFABMS: m/z 438.0125 (MH+). Calcd. for C19H12N5BrCl: m/z 438.0121 ; 8H (CDC13) 4.76 (2H, d, - CH2NH-), 6.32 (1 H, s, H6), 7.00 (1 H, m, -CH2NH-), 7.40 (2H, m, Ar-H), 7.46 (1 H, m, Ar-H), 7.55 (1 H, m, Ar-H), 7.67 (2H, m, Ar-H), 7.71 (1 H, m, Ar-H), 7.75 (1 H, m Ar-H) and 8.10 ppm (1H, s, H2); 8c (CDC13) CH2: 45.5 ; CH: 88.2, 127.2, 130.0, 130.2, 130.4, 130.6, 131.4, 131.6, 131.9, 144.1 ; C: 83.8, 113.4, 118.3, 132.0, 137.8, 138.3, 145.6, 145.9, 158. 0.

EXAMPLE 438 : Reactants: 3-Bromo-7-chloro-5-phenylpyrazolo [1,5-a] pyrimidine (233. 5mg, 0. 681mmoles) (prepared as described in Preparative Example 129); 4-(aminomethyl)benzonitrile (108mg, 0. 817mmoles) (prepared as described in Preparative Example 247 above); diisopropyl ethylamin (0.235mL, 1. 362mmoles) ; anhydrous 1,4-dioxane (5.3mL). Physical data: HRFABMS: m/z 438.0117 (MH+) Calcd. for C20H14N5BrCI : m/z 438.0121 ; aH (CDCl3) 4.80 (2H, d, CH2), 6.30 (1 H, s, H6), 7.01 (1 H, m, NH), 7.40 (2H, m, Ar-H), 7.47 (1 H, m, Ar-H), 7.70 (2H, m, Ar-H), 7.72 (2H, m, Ar-H), 7.80 (1H, m, Ar-H) and 8.10 ppm (1H, s, H2); 8c (CDC13) CH2: 45.8 ; CH: 88.2, 127.2, 127.7, 127.7, 130.2, 130.4, 131.6, 132.9, 132.9, 144.1 ; C: 83.8, 112.2, 118.4, 132.0, 138.2, 141.5, 145.5, 146.0, 158.0.

EXAMPLE 439: 3-Bromo-7-chloro-5- (2-chlorophenyl) pyrazolo [1,5-a] pyrimidine (50mg, 0. 146mmoles) (prepared as described in Preparative Example 129) was dissolved in anhydrous 1,4-dioxane (5mL) in a GeneVac Technologies carousel reaction tube. PS-diisopropyl ethylamin resin (161 mg, 0. 5828mmoles) was

added to each tube. A freshly prepared 1 M solution of the appropriate amine RiNHsin anhydrous 1,4-dioxane (0. 2185mL, 0. 2185mmoles) was added to each tube and the tubes were sealed and heated at 70°C for 78h with magnetic stirring in the reaction block. Each tube was filtered and the resin was washed with anhydrous 1,4-dioxane and then dichloromethane. The combined individual filtrates from each tube were evaporated to dryness and the residues were each re-dissolved in anhydrous 1,4-dioxane (5mL) and placed in GeneVac reaction tubes. To each tube was added PS-isocyanate resin (594mg, 0. 8742mmoles) and PS-trisamine resin (129mg, 0.4371 mmoles) and the tubes were stirred at 25°C for 20h in the reaction block. The resins were filtered off and washed with anhydrous 1,4-dioxane and dichloromethane. The filtrates from each tube were evaporated to dryness and the residues were each chromatographed on a silica gel column using the column size and the eluant shown in Table 36, to give the title compounds.

TABLE 36 FABMS Chromatographic Br <ryT. 15x2. 5cm Ex. Structure MW FABMS Yield Data 'I 15x2. 5cm 440 HN 428. 7 428. 0 81% 0. 5% Methanol, in 0. 5/o Methanol, in dichloromethane I sur N w 20x2cm 441 Ht 428. 7 428. 0 q. g% ichloromethane ; HN 1. 5% Methanol in dichloromethane I/ Br N 15x2. 5cm 442 r'N 428. 7 428. 0 24% ico loromethane ; HN 1. 5/o Methanol in dichloromethane IN N bu 15x2. 2cm 443 HN 463. 8 463. 0 44% Dichloromethane ; 5% Methanol in dichloromethane Cl3 Bu N 15x2. 5cm 444 N Nk Cl 434. 8 434. 1 63% 5% Methanol in HN C dichloromethane Bu s\ r'Y N c) 15x2. 5cm 445 un 448. 8 448. 2 65% 5% Methanol in dichloromethane U Bu N W N-N/CI 15x2. 5cm Dichloromethane ; 446 HN 448. 8 448. 1 40% 0. 5% Methanol in dichloromethane Br Br ar N\ w 15x2. 5cm 447 J, 436. 7 436. 1 72% 0. 5% Methanol in dichloromethane 10 ko Bu I c, 20cm 448 HN 450. 8 450. 0 53% Dichl orom ethane ; 0. 5% Methanol in C, dichloromethane 0 Ber T 20x2cm 449 N-N ci 381. 7 381. 0 44% 1. 5% Methanol in HN CH3 dichloromethane OH

Additional physical data for the compounds are given below : EXAMPLE 440: Physical properties: HRFABMS: m/z 428.0272 (MH+). Calcd. for ClgHq6N5BrCI : m/z 428.0278 ; 8H (CDCl3) 3.28 (2H, dd, C5H4NCH2CH2NH-), 3.94 (2H, ddd, C5H4NCH2CH2NH-), 6.40 (1 H, s, H6), 7.22-7. 29 (3H, m, Ar-H), 7.38- 7.44 (2H, m, Ar-H), 7.51 (1 H, m, Ar-H), 7.68 (1 H, ddd, Ar-H), 7.73 (1 H, Ar-H), 8.18 (1H, s, H2) and 8.68ppm (1H, NH); 8c (CDCI3) CH2 : 36.4, 41.5 ; CH: 87.3, 122.1, 123.6, 127.1, 130.1, 130.1, 131.6, 137.0, 143.8, 149.5 ; C: 83.1, 132.1, 138. 9,145. 7,146. 3,158. 0,158. 1.

EXAMPLE 441: Physical properties: HRFABMS: m/z 428.0272 (MH+). Calcd. for C19H16N5BrCl : m/z 428.0278 ; Sn (CDCI3) 3.12 (2H, dd, C5H4NCH2CH2NH-), 3.77 (2H, ddd, C5H4NCH2CH2NH-), 6.40 (1 H, s, H6), 6.59 (1 H, m, Ar-H), 7.34 (1 H, bm, Ar-H), 7.39-7. 45 (2H, m, Ar-H), 7.52 (1 H, m, Ar-H), 7.62 (1 H, m, Ar-H), 7.75 (1 H, m, Ar-H), 8.05 (1H, s, H2) and 8.63ppm (1H, m, NH); 8c (CDC13) CH2 : 32.7, 43.1 ; CH: 87.5, 127.2, 130.2, 130.3, 131.6, 136.4, 142.9, 148.3, 149.8 ; C: 83.5, 132.0, 138.6, 145.6, 145.9, 158.1.

EXAMPLE 442: Physical properties: HRFABMS: m/z 428.0275 (MH+). Calcd. for C19H16N5BrCI : m/z 428. 0278; 8H (CDCl3) 3.13 (2H, dd, C5H4NCH2CH2NH-), 3.80 (2H, ddd, C5H4NCH2CH2NH-), 6.42 (1 H, s, H6), 6.53 (1 H, m, Ar-H), 7.23 (2H, m, Ar-H), 7.40-7. 46 (2H, m, Ar-H), 7.62 (1 H, m, Ar-H), 7.76 (1 H, m, Ar-H), 8.07 (1 H,

s, H2) and 8.63ppm (1 H, m, NH); 8c (CDC13) CH2: 34.7, 42.5 ; CH : 87.4, 124.5, 124.5, 127.2, 130.2, 130.3, 131.6, 144.0, 150.2, 150.2 ; C: 83.5, 132.0, 138.6, 145.6, 145.9, 146.6, 158.1.

EXAMPLE 443: Physical properties: HRFABMS: m/z 463. 1003 (MH+). Calcd. for C20H25N6BrCI : m/z 463. 1013; #H (CDC13) 1.98 (2H, m, =NCH2CH2CH2NH-), 2.43 (3H, s, NCH3), 2.67 (2H, m, =NCH2CH2CH2NH-), 2.70 (8H, piperazine CH2), 3.58 (2H, m, =NCH2CH2CH2NH-), 6. 32 (1 H, s, H6), 7.37-7. 43 (2H, m, Ar-H), 7.50 (1 H, m, Ar-H), 7.73 (1 H, m, Ar-H), 8.06 (1 H, s, H2) and 8.60ppm (1 H, m, NH); 8c (CDC13) CH3 : 46.1 ; CH2: 24.1, 42. 8, 53.3, 54.6, 54.6, 57.5, 57.5 ; CH: 87. 1,127. 0, 130.0, 130.1, 131.5, 143.4 ; C: 82.7, 132.1, 139.2, 145.7, 146.7, 158.0.

EXAMPLE 444: Physical properties: HRFABMS: m/z 434.0742 (MH+). Calcd. for C19H22N5BrCI : m/z 434.0747 ; 8H (CDC13) 1.72 (1 H, m, CH/CH2), 1. 78-1. 90 (2H, m, CH/CH2), 2.02 (3H, m, CH/CH2), 2.50 (1 H, m, CH/CH2), 2.45 (3H, s, NCH3), 2.51 (1 H, m, CH/CH2), 3.23 (1 H, m, CH/CH2), 3.54 (1 H, m, CH/CH2), 3.60 (1 H, m, CH/CH2), 6.32 (1 H, s, H6), 7. 38-7. 44 (2H, m, Ar-H), 7.51 (1 H, m, Ar-H), 7.75 (1 H, m, Ar-H), 7.96 (1 H, bm, NH) and 8.05 ppm (1 H, s, H2) ; #C (CDCI3) CH3 : 40.7 ; CH2: 22.7, 29.3, 30.1, 39.4, 57.0 ; CH: 64.2, 87.1, 127.1, 130.0, 130.1, 131.6, 143. 8 ; C: 82. 8, 132.1, 139.1, 145.7, 146.4, 158.0.

EXAMPLE 445: Physical properties: HRFABMS : m/z 448. 0910 (MH+). Calcd. for C2oH24N5BrCl : m/z 448.0904 ; 8H (CDC13) 1.90 (4H, m, CH2), 2.00 (4H, m, CH2), 2.84 (2H, m, CH2), 2.95 (4H, m, CH2), 3.51 (2H, m, CH2), 6. 32 (1 H, s, H6), 7.05 (1 H, bm, NH), 7.37-7. 43 (2H, m, Ar-H), 7.50 (1 H, m, Ar-H), 7.73 (1 H, m, Ar-H) and 8.04 ppm (1 H, s, H2); 8c (CDC13) CH2: 23.4, 23.4, 24.8, 26.4, 41.8, 53.9, 53.9, 55.2 ; CH: 87. 3,127. 1,130. 1,130. 2,131. 6,143. 7; C: 83.0, 132.0, 138.9, 145.7, 146.3, 158.1.

EXAMPLE 446: Physical properties: HRFABMS: m/z 448.0548 (MH+). Calcd. for C19H20N5OBrCl : m/z 448.0540 ; 8H (CDCl3) 1.94 (2H, m, CH2), 2.09 (2H, m, CH2), 2.49 (2H, m, CH2), 3.45 (2H, m, CH2), 3.51 (4H, m, CH2), 6.32 (1 H, s, H6), 7.37- 7.44 (3H, m, Ar-H/NH), 7.51 (1H, m, Ar-H), 7.75 (1H, m, Ar-H) and 8.10 ppm

(1H, s, H2); 8c (CDCI3) CH2: 18.0, 26.3, 30.8, 39.2, 39.9, 47.5 ; CH: 87.0, 127.1, 130.1, 130.1, 131.6, 144.1 ; C: 82.9, 132.1, 138.9, 145.6, 146.2, 157.9, 176. 2.

EXAMPLE 447: Physical properties: HRFABMS: m/z 436.0532 (MH+). Calcd. for C18H20N5OBrCl : m/z 436.0540 ; 8H (CDC13) 2.60 (4H, bm,-N (CH2CH2) 20), 2.83 (2H, m, =NCH2CH2NH-), 3.57 (2H, m, =NCH2CH2NH-), 3. 83 (4H, m,- N (CH2CH2) 20), 6.37 (1 H, s, H6), 6.99 (1 H, bm, NH), 7.38-7. 45 (2H, m, Ar-H), 7.51 (1 H, m, Ar-H), 7.75 (1 H, m, Ar-H) and 8.09 ppm (1H, s, H2); 8c (CDCl3) CH2: 38.2, 53.3, 53.3, 56.2, 66.9, 66.9 ; CH: 87.6, 127.1, 130.1, 130.2, 131.6, 143.9 ; C; 83.1, 132.1, 138.9, 145.7, 146.2, 158.1.

EXAMPLE 448: Physical properties: HRFABMS: m/z 450. 0688 (MH+). Calcd. for C19H22N50BrCI : m/z 450.0696 ; aH (CDCl3) 1. 98 (2H, m, =NCH2CH2CH2NH-), 2.58 (4H, m,-N (CH2CH2) 20), 2.67 (2H, m, =NCH2CH2CH2NH-), 3.59 (2H, m, =NCH2CH2CH2NH-), 3.94 (4H, m,-N (CH2CH2) 20), 6.31 (1 H, s, H6), 7.37-7. 44 (2H, Ar-H), 7.51 (1 H, m, Ar-H), 7,78 (1 H, m, Ar-H), 8.08 (1 H, s, H2) and 8.60 ppm (1 H, bm, NH); 8c (CDC13) CH2: 23.7, 42.7, 52.9, 52.9, 58.0, 66.6, 66.6 ; CH: 87. 0,127. 1,130. 0,130. 1,131. 5,143. 6; C: 82.8, 132.1, 139.1, 145.7, 146.7, 158. 0.

EXAMPLE 449: Physical properties: HRFABMS: m/z 381.0114 (MH+). Calcd. for C15H15N40BrCI : m/z 381. 0118 ; #H (CDC13) 1.39 (3H, d, CHCH3), 2.76 (1 H, bm, -OH), 3.71 (1 H, m, =CHCH20H), 3.81 (1H, m, =CHCH20H), 3.88 (1H, m, =CHCH20H), 6.38 (1 H, s, H6), 7.38 (2H, m, Ar-H), 7.48 (1 H, m, Ar-H), 7.68 (1 H, m, Ar-H) and 8.02 ppm (1H, s, H2) ; bC (CDCI3) CH3 : 16.9 ; CH2: 65.0 ; CH: 50.0, 88.0, 127. 1, 130. 1, 130. 3, 131. 4, 143. 8; C: 83. 0, 132. 0, 138. 5, 145. 6, 146. 0, 158. 2.

EXAMPLE 450:

3-Bromo-7-chloro-5- (2-chlorophenyl) pyrazolo [1,5-a] pyrimidine (50mg, 0. 146mmoles) (prepared as described in Preparative Example 129) was dissolved in anhydrous 1,4-dioxane (5mL) in a GeneVac Technologies carousel reaction tube. PS-diisopropyl ethylamin resin (161mg, 0. 5828mmoles) was added to each tube. A freshly prepared solution of the appropriate amine R1NH2 (0. 219mmoles) in anhydrous 1,4-dioxane (0.3mL) was added to each tube, with the exception of Example 99-5 in which the amine was dissolved in 10% MeOH in 1,4-dioxane (0.3mL), and the tubes were sealed and heated at 70°C for 74h with magnetic stirring in the reaction block. Each tube was filtered and the resin was washed with anhydrous 1,4-dioxane and then dichloromethane. The combined individual filtrates from each tube were evaporated to dryness and the residues were each re-dissolved in anhydrous 1,4-dioxane (5mL) and placed in GeneVac reaction tubes. To each tube was added PS-isocyanate resin (594mg, 0. 8742mmoles) and PS-trisamine resin (129mg, 0. 4371 mmoles) and the tubes were stirred at 25°C for 20h in the reaction block. The resins were filtered off and washed with anhydrous 1,4-dioxane and dichloromethane. The filtrates from each tube were evaporated to dryness and the residues were each chromatographed on a silica gel column using the column size and the eluant shown in Table 37, to give the title compounds.

TABLE 37 Ex. Structure MW FABMS Yield Chromatographic M H Data Br --p 15x2. 5cm ; 451 N-N 381. 7 380. 9 66% 0. 5% Methanol in HN CH3 dichloromethane OH Br 20cm ; 381. 7 380. 9 60% 0. 5% Methanol in HNa sCH3 dichloromethane OH Br 15x2. 5cm ; 453 N'N ci 3g1. 7 380. 9 69% 0. 35% Methanol in HUA dichloromethane HO''CHEZ Br BeS 15x2. 5cm ; 454 N-N ci 3g1. 7 380. 9 75% 0. 35% Methanol in HN dichloromethane HO'"CH Bu I 15x2. 5cm ; 455 N X 397. 7 397. 2 84% 1. 5% Methanol in dichloromethane HOLZ OH Bu zizi N, N i CI OH OH Oh Br 15x2. 5cm ; 457 N'N c 395. 7 395. 0 60% 0. 35% Methanol in rCH3 dichloromethane OH OH Br 15x2. 5cm ; 458 N-N i ci 395. 7 396. 3 50% 0. 35% Methanol in HN<ssCH dichloromethane oh OH Br OH N w N, N S Cl 1 5x2. 5cm ; 459 HN 395. 7 396. 0 76% 0. 35% Methanol in dichloromethane OH

Additional physical data for the compounds are given below : EXAMPLE 451: Physical properties: HRFABMS: m/z 381.0115 (MH+). Calcd. for C15H15N40BrCI : m/z 381.0118 ; [α]D25°C+1.4° (c=0.25, MeOH) ; 5H (CDCl3) 1.44 (3H, d, -CHCH3), 3. 77 3. 89 (1 H, dd, CHCH20H), (1 H, dd, CHCH2OH), 3.94 (1 H, m, CHCH20H), 6.41 (1H, s, H6), 6.58 (1 H, d, NH), 7.41 (2H, m, Ar-H), 7.51 (1 H, m, Ar-H), 7.74 (1H, m, Ar-H) and 8.04 ppm (1H, s, H2) ; 8c (CDC13) CH3 : 17.1 ; CH2: 65.5 ; CH: 49.9, 88.0, 127.1, 130.1, 130.2, 131.6, 143.8 ; C: 83.2, 132.1, 138. 7,145. 6,145. 8,158. 1.

EXAMPLE 452: Physical properties: HRFABMS: m/z 381.0115 (MH+). Calcd. for C15H15N40BrCI : m/z 381.0118 ; [α]D25°C+6.5° (c=0. 32, MeOH) ; 8H (CDC13) 1.44 (3H, d,-CHCH3), 3.78 (1 H, dd, CHCH20H), 3.89 (1 H, dd, CHCH20H), 3.96 (1 H, m, CHCH20H), 6.41 (1 H, s, H6), 6.58 (1 H, d, NH), 7.41 (2H, m, Ar-H), 7.51 (1 H, m, Ar-H), 7.75 (1H, m, Ar-H) and 8.04 ppm (1H, s, H2) ; 8c (CDCI3) CH3 : 17.1 ; CH2: 65.5 ; CH: 49.9, 88.0, 127.1, 130.1, 130.3, 131.6, 143.8 ; C: 83.2, 132.1, 138.6, 145.6, 145.8, 158.1.

EXAMPLE 453: Physical properties: HRFABMS: m/z 381.0115 (MH+). Calcd. for C15H15N4OBrCl : m/z 381.0118 ; (a] p25°c +9. 4° (c=0. 27, MeOH) ; 8H (CDCI3) 1.33 (3H, d, CH3), 2.25 (1H, bs, OH), 3.37 (1H, dd, CH2), 3.51 (1H, m, CH2), 4.16 (1H, m, CHOH), 6.35 (1 H, s, H6), 6.93 (1 H, m, NH), 7.40 (2H, m, Ar-H), 7.50 (1 H, m,

Ar-H), 7.70 (1 H, m, Ar-H) and 8.04 ppm (1 H, s, H2) ; 8c (CDCl3) CH3 : 20.8 ; CH2 : 49.2 ; CH: 65.7, 87.8, 127.1, 130.1, 130.2, 131.2, 143.9 ; C : 83.1, 132.1, 138.5, 145.6, 146.6, 158.3.

EXAMPLE 454: Physical properties: HRFABMS: m/z 381.0112 (MH+). Calcd. for C15H15N40BrCI : m/z 381.0118 ; [α]D25°C-3.2° (c=0. 29, MeOH) ; 8H (CDC13) 1.32 (3H, d, CH3), 2. 48 (1H, bs, OH), 3.35 (1H, dd, CH2), 3.49 (1H, m, CH2), 4.15 (1H, m, CHOH), 6.34 (1 H, s, H6), 6.93 (1 H, m, NH), 7.39 (2H, m, Ar-H), 7.49 (1 H, m, Ar-H), 7.68 (1 H, m, Ar-H) and 8.03 ppm (1 H, s, H2) ; 5c (CDC13) CH3 : 20.8 ; CH2 : 49.2 ; CH: 65.7, 87.7, 127.1, 130.1, 130.3, 131.4, 143.9 ; C: 83.0, 132.0, 138.6, 145.6, 146.6, 158.3.

EXAMPLE 455: Physical properties: HRFABMS : m/z 397.0054 (MH+). Calcd. for C15H15N402BrCI : m/z 397.0067 ; [α] D25°C-9.5° (c= 0.28, MeOH) ; aH (CDCl3) 3.18 (2H, bs, OH), 3.47 (1 H, dd, CH2), 3.58 (1 H, dd, CH2), 3.63 (1 H, dd, CH2OH), 3.70 (1H, dd, CH20H), 3.98 (1H, m, CH), 6.35 (1H, s, H6), 7.10 (1H, m, NH), 7.37 (2H, m, Ar-H), 7.46 (1 H, m, Ar-H), 7.64 (1 H, m, Ar-H) and 8.01 ppm (1 H, s, H2) ; 8c (CDC13) CH2 : 44.7, 64.0 ; CH: 69.7, 87.7, 127.0, 130.1, 130.3, 131.3, 143.9 ; C: 82.9, 132.0, 138. 4,145. 4,146. 7, 158. 3.

EXAMPLE 456: This enantiomer may be prepared by essentially the same manner as described above.

EXAMPLE 457: Physical properties: HRFABMS: m/z 395.0260 (MH+). Calcd. for C16H17N4OBrCl : m/z 395.0274 ; [α]D25°C-34.3° (c= 0.28, MeOH) ; 8H (CDCl3) 1.08 (3H, dd, CH3), 1. 78 (1H, m, CH2), 1.86 (1 H, m, CH2), 2.35 (1 H, bs, CH20H), 3.71 (1H, m, CHNH), 3.81 (1 H, dd, CH20H), 3.90 (1 H, dd, CH2OH), 6. 42 (1 H, s, H6), 6.53 (1H, m, NH), 7.41 (2H, m, Ar-H), 7.51 (1H, Ar-H), 7.75 (1 H, m, Ar-H) and 8.04 ppm (1H, s, H2); 8c (CDCl3) CH3 : 10.5 ; CH2: 24.5, 63.7 ; CH: 55.9, 88.0, 127.1, 130.1, 130.2, 131.6, 143.8 ; C: 83.2, 132.1, 138.6, 145.6, 146.3, 158.1.

EXAMPLE 458: Physical properties: HRFABMS: m/z 395.0274 (MH+). Calcd. for C16H17N40BrCI : m/z 395.0274 ; [α]D25°C+27.5° (c= 0.25, MeOH) ; Sn (CDCl3) 1.05

(3H, dd, CH3), 1.76 (1H, m, CH2), 1.85 (1H, m, CH2), 2.28 (1H, bs, CH2OH), 3.67 (1 H, m, CHNH), 3.77 (1 H, dd, CH20H), 3.84 (1H, dd, CH20H), 6.49 (1H, s, H6), 6.66 (1 H, m, NH), 7.39 (2H, m, Ar-H), 7.49 (1 H, Ar-H), 7.71 (1 H, m, Ar-H) and 8.04 ppm (1H, s, H2) ; 8c (CDC13) CH3 : 10.5 ; CH2: 24.3, 63.3 ; CH: 56.1, 88.0, 127.1, 130.1, 130.3, 131.5, 143.8 ; C: 83.0, 132.1, 138.6, 145.6, 146.3, 158.2.

EXAMPLE 459: Physical properties: HRFABMS: m/z 395.0264 (MH+). Calcd. for C16H17N4OBrCl : m/z 395.0274 ; 8H (CDC13) 1.77 (2H, m, -NHCH2CH2CH2CH2OH), 1.90 (1H, bm, -NHCH2CH2CH2CH2OH), 1.93 (2H, m,-NHCH2CH2CH2CH20H), 3.54 (2H, m,-NHCH2CH2CH2CH20H), 3.77 (2H, m,-NHCH2CH2CH2CH20H), 6.37 (1 H, s, H6), 6.72 (1H, m, -NHCH2CH2CH2CH2OH), 7.41 (2H, m, Ar-H), 7.51 (1 H, m, Ar-H), 7.75 (1 H, m, Ar-H) and 8.06 ppm (1H, s, H2); 8c (CDC13) CH2: 25.7, 29.7, 42.2, 62.2 ; CH: 87.4, 127.1, 130.1, 130.2, 131.6, 143.8 ; C: 83.1, 132.1, 138.8, 145.6, 146.3, 158.1.

EXAMPLE 460: 4- { [3-BROMO-5- (2-CHLOROPHENYL) PYRAZOLO [1, 5-a] PYRIMIDIN-7- YLAMINO] METHYL} PIPERIDINE-1-CARBOXYLIC ACID AMIDE : A. 4- { [3-BROMO-5- (2-CHLOROPHENYL) PYRAZOLO [1,5-a] PYRIMIDIN-7- YLAMINO] METHYL} PIPERIDINE-1-CARBOXYLIC ACID tert-BUTYL ESTER:

3-Bromo-7-chloro-5- (2-chlorophenyl) pyrazolo [1, 5-a] pyrimidine (300mg, 0. 875mmoles) (prepared as described in Preparative Example 129) was dissolved in anhydrous 1,4-dioxane (6. 8mL). 4-(aminomethyl)piperidine-1- carboxylic acid tert-butyl ester (225mg, 1. 05mmoles) and diisopropyl ethylamine (0.3055mL, 1. 75mmoles) were added and the mixture was heated at 75°C for 24h. The solution was evaporated to dryness and the residue was chromatographed on a silica gel column (1 5x5cm) using dichloromethane as the eluant to give 4- { [3-bromo-5- (2-chlorophenyl) pyrazolo [1,5-a] pyrimidin-7- ylamino] methyl} piperidine-1-carboxylic acid tert-butyl ester (461.2mg, 100%): FABMS: m/z 520.1 (MH+) ; HRFABMS: m/z 520.1111 (MH+). Calcd. for C23H28N502BrCl : m/z 520. 1115 ; 8H (CDC13) 1.30 (2H, m, CH2), 1.51 (9H, s,- COOC (CH3) 3), 1.85 (2H, d, CH2), 1.95 (1H, m, CH), 2.76 (2H, m, CH2), 3. 40 (2H, m, CH2), 6.37 (1 H, s, H6), 6.55 (1 H, m, NH), 7.42 (2H, m, Ar-H), 7.52 (1 H, m, Ar-H), 7.76 (1 H, m, Ar-H) and 8.07 ppm (1 H, s, H2) ; 6c (CDCI3) CH3 : 28. 5, 28.5, 28.5 ; CH2 : 29.1, 29.1, 43.5, 43.5, 47.9 ; CH: 36.3, 87.5, 127.2, 130.2, 130.3, 131.6, 143.9 ; C: 79.7, 83.3, 132.1, 138.6, 145.4, 146.3, 154.7, 158.1.

B. [3-BROMO-5- (2-CHLOROPHENYL) PYRAZOLO [1,5-a] PYRIMIDIN-7- YL] PIPERIDIN-4-YLMETHYLAMINE :

4-{[3-Bromo-5-(2-chlorophenyl) pyrazolo [1, 5-a] pyrimidin-7- ylamino] methyl} piperidine-1-carboxylic acid test-butyl ester (441 mg, 0. 847mmoles) (prepared as described in Example 460, Step A above) was dissolved in methanol (4.5mL) and 10% (v/v) conc. sulfuric acid in 1,4-dioxane (11. 46mL) was added. The mixture was stirred at 25°C for 0.5h. The product was worked up as described in Preparative Example 241, step B and chromatographed on a silica gel column (15x5cm) using 8% (10% conc. ammonium hydroxide in methanol)-dichloromethane as the eluant to give [3- bromo-5- (2-chlorophenyl) pyrazolo [1,5-a] pyrimidin-7-yl] piperidin-4-ylmethylamine (314.4mg, 88%): FABMS: m/z 420.0 (MH+) ; HRFABMS: m/z 420.0585 (MH+).

Calcd. for C18H2oN5BrCl : m/z 420.0591 ; 8H (CDCl3) 1.34 (2H, m, CH2) s 1.86 (2H, m, CH2) s 1. 91 (1H, m, CH), 2.10 (1H, bm, piperidine-NH), 2.67 (2H, m, CH2), 3.18 (2H, m, CH2), 3. 38 (2H, m, CH2), 6.37 (1H, s, H6), 6.53 (1H, m, NH), 7.42 (2H, m, Ar-H), 7.52 (1 H, m, Ar-H), 7.76 (1 H, m, Ar-H) and 8. 06 ppm (1 H, s Ar-H); bc (CDC13) CH2: 31.2, 31.2, 46.2, 46.2, 48.4 ; CH: 36.4, 89.5, 127.1, 130.1, 130.5, 131.6, 143.8 ; C: 83.2, 132.1, 138.9, 145.6, 146.4, 158.1.

C. 4- { [3-BROMO-5- (2-CHLOROPHENYL) PYRAZOLO [1,5-a] PYRIMIDIN-7- YLAMINO] METHYL} PIPERIDINE-1-CARBOXYLIC ACID AMIDE :

[3-Bromo-5- (2-chlorophenyl) pyrazolo [1,5-a] pyrimidin-7-yl] piperidin- 4-ylmethylamine (57mg, 0. 136mmoles) (prepared as described in Example 460, Step B above) was dissolved in anhydrous dichloromethane (1.2mL) and trimethylsilylisocyanate (0.091 mL, 0. 679mmoles) was added. The mixture was stirred at 25°C for 2.5h. The mixture was diluted with dichloromethane and washed with saturated aqueous sodium bicarbonate. The organic layer was dried (MgSO4), filtered and evaporated to dryness. The residue was chromatographed on a silica gel column (30x2.5cm) using 3% (10% conc. ammonium hydroxide in methanol)-dichloromethane as the eluant to give 4- { [3- bromo-5- (2-chlorophenyl) pyrazolo [1,5-a] pyrimidin-7-ylamino] methyl} piperidine-1- carboxylic acid amide (53.7mg, 86%) : FABMS: m/z 463.1 (MH+) ; HRFABMS: m/z 463.0647 (MH+). Calcd. for C19H21N60BrCI : m/z 463.0649 ; 8H (d6-DMSO) 1.09 (2H, m, CH2), 1.63 (2H, m, CH2), 1.87 (1H, m, CH), 2.60 (2H, m, CH2), 3.53 (2H, bm, CONH2), 3.91 (2H, d, CH2), 6.52 (1 H, s, H6), 7.50 (2H, m, Ar-H), 7.62 (2H, m, Ar-H), 8.33 (1 H, s, H2) and 8.52 ppm (1 H, m, NH); 8c (d6-DMSo) CH2: 30.1, 30.1, 44.2, 44.2, 47.7 ; CH: 36.4, 88.2, 128. 1,130. 7,131. 4,132. 1,147. 9; C: 82.1, 132.1, 139.4, 145.7, 147.9, 158.1, 158.8.

EXAMPLE 461: 2- {2- [3-BROMO-5- (2-CHLOROPHENYL) PYRAZOLO [1,5-a] PYRIMIDIN-7- YLAMINO] ETHYL} PIPERIDINE-1-CARBOXYLIC ACID AMIDE :

A. 2- {2- [3-BROMO-5- (2-CHLOROPHENYL) PYRAZOLO [1,5-a] PYRIMIDIN-7- YLAMINO] ETHYL} PIPERIDINE-1-CARBOXYLIC ACID tert-BUTYL ESTER: 3-Bromo-7-chloro-5- (2-chlorophenyl) pyrazolo [1,5-a] pyrimidine (400mg, 1. 166mmoles) (prepared as described in Preparative Example 129) was dissolved in anhydrous 1,4-dioxane (5.7mL). 2-Aminoethylpiperidine-1- carboxylic acid tert-butyl ester (266mg, 1. 166mmoles) and diisopropyl ethylamin (0.409mL, 2. 33mmoles) were added and the mixture was heated at 75°C for 48h. Additional diisopropyl ethylamine (0.204mL, 1. 166mmoles) was added and the heating was continued for a total of 58h. The solution was evaporated to dryness and the residue was chromatographed on a silica gel column (15x5cm) using dichloromethane followed by 0.3% (10% cone. ammonium hydroxide in methanol)-dichloromethane as the eluant to give 2-{[3- bromo-5-(2-chlorophenyl) pyrazolo [1, 5-a] pyrimidin-7-ylamino] ethyl} piperidine-1- carboxylic acid tert-butyl ester (491. 1 mg, 79%): FABMS: m/z 534.1 (MH+) ; HRESIMS : m/z 534.12797 (MH+). Calcd. for C24H30N502BrCI : m/z 534.12714 ; 8H (CDCl3) 1.50 (1 H, m, CH2), 1. 51 (9H, s, COOC (CH3) 3), 1. 57 (2H, m, CH2), 1.68 (2H, m, CH2), 1.76 (2H, m, CH2), 2.24 (1H, bm, CH2), 2.82/3. 40/3.54/4. 08/4. 51 (5H, m, CH/CH2), 6.34 (1 H, s, H6), 7.41 (2H, m, Ar-H),

7.51 (1 H, m, Ar-H), 7.76 (1 H, m, Ar-H) and 8.08 ppm (1 H, s, H2); 8c (CDCI3) CH3 : 28.5, 28.5, 28.5 ; CH2: 19.2, 25.5, 29.2, 29.2, 39.2, 67.1 ; CH :-47. 4,87. 1,127. 1, 130.1, 130.1, 131.6, 143.9 ; C: 80. 0,83. 0,132. 1,138. 9,145. 7,146. 2,158. 0.

B. [3-BROMO-5- (2-CHLOROPHENYL) PYRAZOLO [1,5-a] PYRIMIDIN-7-YL]- (2-PIPERIDIN-2-YLETHYL) AMINE : 2- { [3-Bromo-5- (2-chlorophenyl) pyrazolo [1,5-a] pyrimidin-7- ylamino] ethyl} piperidine-1-carboxylic acid tert-butyl ester (465mg, 0. 869mmoles) (prepared as described in Example 461, Step A above) was dissolved in methanol (4.5mL) and 10% (v/v) conc. sulfuric acid in 1,4-dioxane (11. 76mL) was added. The mixture was stirred at 25°C for 1.5h. The product was worked up as described in Preparative Example 241, step B and chromatographed on a silica gel column (15x5cm) using 3.5% (10% conc. ammonium hydroxide in methanol)-dichloromethane as the eluant to give [3-bromo-5- (2- chlorophenyl) pyrazol [1,5-a] pyrimidin-7-yl] piperidin-2-ylethyl) amine (365.6mg, 97%): FABMS: m/z 434.1 (MH+) ; HRFABMS: m/z 434.0726 (MH+). Calcd. for C19H22N5BrCI : m/z 434.0747 ; 8H (CDC13) 1.24 (1 H, m, CH2), 1.41 (1 H, m, CH2) 1.49 (1 H, m, CH2), 1.66 (1 H, m, CH2), 1.73 (1 H, m, CH2), 1. 81 (1 H, m, CH2), 1.88 (2H, m, CH2), 2.68 (1 H, m, CH2), 2.78 (1 H, m, CH2), 3.20 (1 H, m, CH), 3.55 (1 H, m, CH2), 3.60 (1H, m, CH2), 6.32 (1H, s, H6), 7.41 (2H, m, Ar-H), 7.51 (1H, m, Ar-H), 7.74 (1 H, m, Ar-H), 7.78 (1 H, m, NH) and 8.05 ppm (1 H, s, H2); 8c (CDC13) CH2: 24.7, 26.8, 33.1, 35.2, 40.3, 47.0 ; CH: 55.7, 87.2, 127.1, 130.0, 130.1, 131.5, 143.8 ; C: 82.9, 132.1, 139.0, 145.7, 146.5, 158.1. C. 2- {2- [3-BROMO-5- (2-CHLOROPHENYL) PYRAZOLO [1, 5-a] PYRI M I D I N-7- YLAMINO] ETHYL} PIPERIDINE-1-CARBOXYLIC ACID AMIDE :

[3-Bromo-5- (2-chlorophenyl) pyrazolo [1,5-a] pyrimidin-7-yl] piperidin-2- ylethyl) amine (200mg, 0. 46mmoles) (prepared as described in Example 461, Step B above) was dissolved in anhydrous dichloromethane (2mL) and trimethylsilylisocyanate (0.31 mL, 2. 3mmoles) was added. The mixture was stirred at 25°C for 1.25h. Additional trimethylsilylisocyanate (0. 155mL, 1. 1 5immoles) was added and the stirring was continued for a total of 3h. The mixture was diluted with dichloromethane and washed with saturated aqueous sodium bicarbonate. The organic layer was dried (MgSO4), filtered and evaporated to dryness. The residue was chromatographed on a silica gel column (30x2.5cm) using 2% (10% conc. ammonium hydroxide in methanol)- dichloromethane as the eluant to give 2- {2- [3-bromo-5- (2- chlorophenyl) pyrazol [1,5-a] pyrimidin-7-ylamino] ethyl} piperidine-1-carboxylic acid amide (106. 3mg, 48%) : FABMS: m/z 477.0 (MH+) ; HRFABMS: m/z 477.0804 (MH+). Calcd. for C20H23N60BrCI : m/z 477.0805 ; 8H (d6-DMSO) 1.29 (1 H, m, CH2), 1.52 (5H, m, CH2), 1.72 (1H, m, CH2), 2.05 (1H, m, CH2), 2.51 (2H, s, CONH2), 2.79 (1H, dd, CH), 3.31 (1H, m, CH2), 3.34 (1H, m, CH2), 3.76 (1 H, m, CH2), 4.30 (1 H, bm, CH2), 6.42 (1 H, s, H6), 7.50 (2H, m, Ar-H), 7.60 (1 H, m, Ar-H), 7.63 (1 H, m, Ar-H), 8.29 (1H, s, H2) and 8.38 ppm (1 H, dd, NH); 8c (d6- DMSO) CH2: 18.6, 25.2, 28. 2,38. 4,38. 6,54. 8; CH: 46.7, 86.6, 127.1, 129.7, 130.3, 131.0, 143.4 ; C: 81.2, 131.0, 138.7, 145.1, 146.4, 158.2.

EXAMPLE 462:

To a solution of the compound prepared in Example 204 (1. 11 g, 2.12 mmol) in anhydrous acetonitrile (20 mL) was added TMSI (1.70 g, 8.52 mmol), dropwise at ambient temperature. After 10 minutes the acetonitrile was removed in vacuo. The resulting yellow foam was treated with 2 N HCI solution (7 mL) and then washed immediately with Et20 (5X). The pH of the aqueous was adjusted to 10 with 50 % NaOH (aq) and the product was isolated by saturation of the solution with NaCI (s) followed by extraction with CH2CI2 (5X) to give the crystalline product (733 mg, 89% yield). MH+ = 387; m. p. = 207. 5 °C EXAMPLES 463-472 : By essentially the same procedure set forth in Example 462 only substituting the compounds shown in Column 2 of Table 38, the compounds shown in Column 3 of Table 38 were prepared.

TABLE 38 Ex. Column 2 Column 3 CMPD 463 Cbz, han 463 CbzsNa Br HN) Br MH = 403 H NMR (300MHz, CDCI3) 8 8. 52 (s, i N-N 1 H), 8. 38 (d, 1H), l NH 8. 04 (s, 1 H), 7. 78 (d, gNH f 1H), 7. 65 (t, 1H), 6. 18 (s, 1H), 4. 89 (s, + 2H), 3. 26-3. 21 (d, + N, 2H), 2. 96-2. 70 (m, 0 3H), 2. 05-1. 78 (m, 4H). 464 CbzN HN Br Br MH+ = 454 m. p. = 175. 4 °C oye- NU NU NH NH O 0-1 465 Cbz, N ber HN Yield = 87 Br MH+ = q. 70 m. p. = 220 °C y WN_N SN_N m. pt (hydrochloride NH NH salt) = 164. 3 °C I I N N 1 11 S-N-N 466 Cbz, N 466 CbzsNa Br HNX Br MH = 464 m. p. = 206 °C N-N WN_N/2 H NH . NH NH 467 Cbz, HN Br MH+ = 411 m. p. = 169. 5 °C N-N N-N NH NH C C CN CN Cbz, 468 N Br HN Br MH+ = 334 m. p. = 176. 2 °C NH NH , NH 469 CbN HN Br Br MH+ = 465 NH NH m. p. = 250. 4 °C NU NU NH NH 470 gr Br 470 Br Br MH+ = 387 N m. p. = 68. 5 °C null zon NH NH IN IN Nz 471Cbz N MH+ = 387 "yin N N'l N-N N w non IN IN Q kan N \ N 472 Br Br I-mp = 230-232 CbzNo 9, N4 HN9X<, N4 2. M+H = 396 WN_N W N-N HN HN /1 1 HAN NON NON N NH2 NH2 472 CbzN Br HN Br . 10 1. mp = 157-160 C'yin N'N N'N HN HN ZON N HN-'J HN-/i EXAMPLE 473: Step A:

A solution of the sulfonic acid (560 mg, 1.17 mmol) in 5 mL of dry DMF was cooled to 0 °C and SOCI2 (278 mg, 2.34 mmol) was added. The reaction mixture was brought to RT and stirred overnight. The next day the contents were poured on ice and the pH was carefully adjusted to 8. The product was extracted in to EtOAc and the solvent was removed after drying (Na2SO4) to provide 240 mg (41 %) of the crude sulfonyl chloride which was used for the next

step without further purification.'H NMR (CDC13) 6 8.20-8. 10 (m, 1H), 8.10-7. 95 (m, 3H), 7.65 (d, 2H), 7.45-7. 35 (m, 1H), 7.35-7. 20 (m, 1H), 7.15-7. 05 (m, 1H), 6.95 (t, 1H), 4.85 (d, 2H).

Step B:

A solution of compound prepared in Example 473, Step A (120 mg, 0.24 mmol) in 10 mL of THF was treated with 2 mL of 1 M MeNH2 (2.00 mmol) in THF at RT overnight. The solvent was removed and the residue was purified by chromatography (silica, hexane: EtOAc (4: 1#1 : 1) ) to provide 56 mg (48%) of the sulfonamide. 1H NMR (DMSO-d6) 5 9.05 (t, J = 9 Hz, 1H), 8.35 (s, 1H), 7.90 (t, J = 7.5 Hz, 1 H), 7.75 (d, J = 9 Hz, 2H), 7.62 (d, J = 9 Hz, 2H), 7.55-7. 46 (m, 1 H), 7.45-7. 38 (m, 1H), 7.38-7. 25 (m, 1H), 6.50 (s, 1H), 4.80 (d, 2H), 3.30 (s, 3H) LCMS: MH+ = 492.1 EXAMPLE 474 :

By essentially the same procedure set forth in Example 473, only substituting dimethylamine, the above compound was prepared. 1H NMR (CDC13)

88. 14 (t, J = 9 Hz, 1H), 8.00 (s, 1H), 7.76 (d, J=9Hz, 2H), 7.54 (d, J = 9 Hz, 2H), 7.34-7. 44 (m, 1H), 7.26 (t, J = 9 Hz, 1 H), 7.14-7. 04 (m, 1H), 6.93 (t, J= 6 Hz, 1 H), 6.45 (s, 1 H), 4.75 (d, 2H), 2.70 (s, 6H) LCMS: Mu+ = 504.2 EXAMPLE 475: A mixture of the compound prepared in Example 129 (300 mg, 0.66 mmol), NaOH (5 g), CH30H-H20 (100 mL, 90: 10) was stirred at 25 C for about 15 h. Progress of hydrolysis was checked by TLC. Reaction mixture was concentrated to remove methanol. The concentrate was diluted with 50 mL water, and extracted with ether to remove any un-reacted ester. Aqueous solution, thus obtained, was neutralized with 3 N HCI to pH 4 to obtain free acid, filtered and washed repeatedly with water. The acid was dried under vacuum ( 270 mg, 93%) and used without further purification.

Example 476-479: By essentially the same procedure set forth in Example 475 only substituting the compounds in Column 2 of Table 39, the compounds in Column 3 of Table 39 were prepared.

Table 39 Ex. Column 2 Column 3 CMPD 476 I W Br I W Br Yield = 82% LCMS : MH+= 365 /NiN Ho. HN HN1 HN I C02Me CO2H Yield = 82% 4 7 ,- Br LCMS : MH+= 379 F F HO HAN C02Et C02H Yield = 72% COsEt"COsH 47R. . , Yie) d = 72% ! Br "1 Br N LCMS : MH+ 393 N F N-N F N-N HN HN CO2Et C02H 479 s ;''. Br= 479 Br Br Yield = 70% LCMS : MH+= 407 N HN HN x ÇO2Et CO2H F N-N F N-N HO HAN C02Me C02H +

Additional data for select examples shown below : Example 476: 1H NMR (CDCl3) # 8.15 (m, 2H), 8.0 (m, 1 H), 7.6 (m, 1 H), 7.3 (m, 2H), 6.6 (s, 1 H), 4.2 (d, 2H).

Example 477: 1H NMR (CDCl3) # 8. 15 (dt, 1H), 8.0 (s, 1H), 7.4 (m, 1H), 7.25 (dd, 1H), 7.15 (dd, 1H), 7.0 (t, 1H), 6.5 (s, 1H), 3.8 (dt, 2H), 2.6 (t, 2H).

Example 479 : 1H NMR (CDCI3) 8 8.15 (dt, 1H), 8.0 (s, 1H), 7.4 (m, 1H), 7.25 (dd, 1H), 7.15 (dd, 1H), 6.8 (t, 1H), 3.5 (dt, 2H), 2.4 (t, 2H), 1.8 (m, 4H).

EXAMPLE 480:

A mixture of the acid from Example 475 (85mg, 0.193 mmol) and Et3N (20 mg, 0.193 mmol) in THF (20 mL) was stirred at 25 C for 15 min. Isobutyryl chloroformate (28mg, 0.205 mmol) was added to the reaction mixture and stirred for 10 min followed by addition of NH40H solution (0.5 mL). The reaction mixture was stirred for 1 hr and concentrated to dryness. The dry mass was purified by column chromatography.

EXAMPLES 481-509: By essentially the same procedure set forth in Example 480 only substituting the carboxylic acid shown in Column 2 of Table 40 and the amine shown in Column 3 of Table 40, the compounds shown in Column 4 of Table 40 were prepared.

Table 40 Ex. Column 2 Column 3 Column 4 CMPD 481 CH3NH2 0) Br N Yield = N F N-N 88% zon LCMS : han HN MH+= 454 n NHCH3 OH 482 (CH3) 2NH N er I i Yield=80 rv\ °lo zon F N i/ N han LCMS HN MH+ , 468 O N (CH3) 2 0 OH 483 CH3NH2 Br Yield=70 -', Br Br % ws¢ « NrS F iNN/2 LCMS F YN_N HN MH = F N-N LCMS I I 'NiN Y HN 454. NHCH3 \ OH 0 O 484 Yield=75 Br N Br NH2 % F N-N LCMS F YN N HN MH = HN 482. 1 1 O N_ \ H 0 OH su Br Yield=71 z Br NH2 I Y F N-N HN LCMS HN MH+ 480. 1 9 xi O NU 0 OH 486 bu N YNH2 F % \ Nz Zon F N // Lems HN MH+ = 494. 1 o H O OU 47 Yield=75 N B/j % NHZ OH __ _ Y F N_N HN) 494. 1 A O F N-N HN 494. 1 HN ç OH H 488 \/n Br Yield=75 -ton bar Br NH2 % =f F W NN/4MgH6+ 1 HNa b F N-N HN 496. 1 HN O OH H H 489 Br Br Yield=75 Bu bu -yin_ NHZ F NN LCMS HN HN MH+ 508. 1 O OH 0 N_ ' H 490 Br Yield=78 Br roo N % Br //N NHZ F N,/l LCMS F » HN LCMS N han HN 524. 1 \ H I J 0 OH 491 Br Yield=73 N Br N ber N zon N,// N HAN HN 508. 1 \ O NEZ O OH 0 OH 0 No X CN , ;, -yin_ Br N % N N HAN HN 510. 1 F O O oh 493 OH llo / Yield=76 Nez NN'% F N-N HN LCMS HN MH+ 526. 1 o s O OH 494 Br Br Br (N) N Yield=76 'N '% QsoNuN N-% _con HN 523. 1 A O 0 OH ON", O OH Nw 495 CH3 Yield=76 Br N Br % Br 1 CNJ F w H 523. 1 N HN nu N OH \ oh 496 oH o Br Br N Br Yield=51 F N OH F N-% "LCM HAN HN MH+ _ 484. 1 0 N ZU 0 oh 497 nu2 Bu Yield=66 N N F N- to<oNur : t O F YN N % F N-N HN MH+ HN 537. 1 /\ Y OH H n-nH 498 NH2-Yield=76 Br N Br % bu N--CH3 N LCMS Y HN MH = HN J 551. 2 W N-ION H n OH 499 Inl NH2 Br Yield=79 Bu bu % N \ N. ' F \ LCMS N HN iNN/@ HN MH+ = 6 , 552. 1 0 O Nz 0 OH H 500 I Yieid=80 Ber F Br W Y % F N N HN 549. 1 HO / HN) N \ X OANX O OH H v O oh 501 H2Nv/n Br Yield=80 ber % F NN LCMS F YN N HN MH = F \ N' i/+_ N HN MH _ HN 478. 1 \ OOH. OH H 502 H2N n Br Yield=80 ber % Br F N N LCMH+ zon F N-N HN 468. 1 N han HN \ O NU n oh 503 H2N CF3 H Br Yield=80 N Br % N F N-N MH+ F y "522. 1 N ho HN J NCF3 H oh Yield=82 /j i S F N /% zon LCMS N HAN HN MH+ _ F YN_N l HN LCMS 528. 1 \ O NS H 505 CH3NH2 Yield=60 Br /jazz N F N-N MH-'= 3 2 N HN HN. OH 3 506/\ A Yield=60 Br ber /j i H F NN LCMH+ _ ° 448. 1 N HN II N. J HN--*, OH 0 0 507 Yield=70 Br Br i i % N \ N'i MH+ _ zon \ N' S N HNN J 464. 1 HN rOH 0 508 Br Yield=50 ber % -tu N Y N \ HNN MH 436. 1 Oh 508 cbz, CH3NH2 cbz, Yield = . 10 N Br N Br g MU N-N N-N 577 HN J<OH H 436. 1 . 510o8 CbZN'\ Br CH3NH2 cbZsN B 95M72HId NH NH C02H N H

Additional data for select examples given below : Example 481 : 1H NMR (CDCl3) # 8.15 (dt, 1H), 8.0 (s, 1H), 7.7 (d, 2H), 7.4 (s, 1H), 7.35 (d, 2H), 7.25 (dd, 1H), 7.1 (dd, 1H), 6.95 (t, 1H), 6.5 (s, 1H), 6.25 (bs, 1H), 4.7 (d, 2H), 3.0 (d, 3H).

Example 482: 1H NMR (CDCl3) # 8. 15 (dt, 1H), 8.0 (s, 1H), 7.45-7. 35 (m, 4H), 7.25 (d, 2H), 7.15 (dd, 1H), 6.7 (t, 1H), 6.5 (s, 1H), 4.7 (d, 2H), 3.1 (s, 3H), 3.0 (s, 3H).

Example 483: 1H NMR (CDCl3) # 8.15 (dt, 1H), 8.0 (s, 1H), 7.8 (bs, 1H), 7.7 (d, 1 H), 7.5-7. 3 (m, 3H), 7.25 (d, 1 H), 7.15 (dd, 1 H), 6.75 (t, 1 H), 6.5 (s, 1 H), 6.2 (bs, 1H), 4.7 (d, 2H), 3.0 (d, 3H).

Example 484 : 1H NMR (CDCl3) # 8.15 (dt, 1H), 8.0 (s, 1H), 7.7 (d, 2H), 7.4 (d, 2H), 7.35 (m, 1H), 7.25 (dd, 1H), 7.15 (dd, 1H), 6.8 (t, 1H), 6.5 (s, 1H), 6.0 bs, 1 H), 4.7 (d, 2H), 4.25 (m, 1 H), 1.2 (d, 6H).

Example 485: 1H NMR (CDCl3) # 8.15 (dt, 1H), 8.0 (s, 1H), 7.7 (d, 2H), 7.4 (d, 2H), 7.35 (s, 1 H), 7.25 (dd, 1 H), 7.1 (dd, 1 H), 6.9 (t, 1 H), 6.5 (s, 1 H), 6.3 (t, 1 H), 4.7 (d, 2H), 2.9 (m, 1H), 0.8 (bt, 2H), 0.6 (bt, 2H).

Example 486 : 1H NMR (CDCl3) # 8.15 (dt, 1H), 8.0 (s, 1H), 7.8 (d, 2H), 7.4 (d, 2H), 7.35 (d, 1H), 7.25 (dd, 1H), 7.1 (dd, 1H), 6.9 (t, 1H), 6.5 (s, 1H), 6.2 (t, 1H), 4.7 (d, 2H), 3.3 (dd, 2H), 1.05 (m, 1 H), 0.5 (m, 2H), 0.25 (m, 2H).

Example 487 : 1H NMR (CDCl3) # 8. 15 (dt, 1H), 8. 0 (s, 1H), 7.7 (d, 2H), 7.4 (d, 2H), 7.35 (m, 1H), 7.25 (dd, 1H), 7.15 (dd, 1H), 6.85 (t, 1H), 6.5 (s, 1H), 6.2 (bs, 1 H), 4.7 (d, 2H), 4.6 (m, 1 H), 2.4 (m, 2H), 1.95 (m, 1 H), 1.75 (m, 2H).

Example 488: 1H NMR (CDCl3) # 8.5 (t, 1H), 8.15 (dt, 1H), 8.0 (s, 1H), 7.7 (d, 2H), 7.4 (d, 2H), 7.35 (m, 1H), 7.25 (dd, 1H), 7.15 (dd, 1H), 6.8 (t, 1H), 6.5 (s, 1 H), 5.9 (bs, 1 H), 4.7 (d, 2H), 1.4 (s, 9H).

Example 489: 1H NMR (CDCl3) # 8.15 (dt, 1H), 8. 0 (s, 1H), 7.7 (d, 2H), 7.4 (d, 2H), 7.35 (m, 1H), 7.25 (dd, 1H), 7.15 (dd, 1H), 6.8 (t, 1H), 6.5 (s, 1H), 6.0 bs, 1 H), 4.7 (d, 2H), 4.4 (m, 1 H), 2.05 (m, 2H), 1.7 (m, 4H), 1.4 (m, 2H).

Example 490 : 1H NMR (CDCl3) # 8.15 (dt, 1H), 8. 0 (s, 1H), 7.7 (d, 2H), 7.4 (d, 2H), 7.35 (m, 1H), 7.25 (dd, 1H), 7.15 (dd, 1H), 6.8 (t, 1H), 6.5 (s, 1H), 6.5 (bs, 2H), 4.7 (d, 2H), 4.1 (m, 1 H), 3.9-3. 7 (m, 3H), 3.3 (m, 1 H), 2.0-1. 9 (m, 4H).

Example 491 : 1H NMR (CDC13) 8 8. 15 (dt, 1 H), 8.0 (s, 1 H), 7.45-7. 35 (m, 5H), 7.25 (dd, 1 H), 7.1 (dd, 1 H), 6.8 (t, 1 H), 6.5 (s, 1 H), 4.7 (d, 2H), 3.7 (bs, 2H), 3. 3 ( bs, 2H), 1.7 (bs, 4H), 1.5 (bs, 2H).

Example 492: 1H NMR (CDCl3) # 8. 15 (dt, 1 H), 8.0 (s, 1H), 7.45-7. 35 (m, 5H), 7.25 (dd, 1H), 7.1 (dd, 1 H), 6.85 (t, 1 H), 6.5 (s, 1 H), 4.7 (d, 2H), 3.8-3. 4 (bm, 8H).

Example 493 : 1H NMR (CDC13) # 8. 15 (dt, 1 H), 8.0 (s, 1 H), 7.45-7. 35 (m, 5H), 7.25 (dd, 1H), 7.1 (dd, 1H), 6.80 (t, 1H), 6.5 (s, 1H), 4.7 (d, 2H), 4.0 (m, 2H), 3.6 (m, 2H), 2.8-2. 45 (m, 4H).

Example 494 :'H NMR (CH30D) # 8. 15 (s, 1 H), 8.0 (dt, 1 H), 7.45-7. 35 (m, 5H), 7.25 (dd, 1 H), 7.1 (dd, 1H), 6.80 (t, 1 H), 6.5 (s, 1 H), 4.7 (d, 2H), 3.7 (bs, 2H), 3.4 (bs, 2H), 2.5-2. 4 (m, 4H), 2.2 (s, 3H).

Example 495 1H NMR (CDCI3) 8 8.15 (dt, 1H), 8. 0 (s, 1H), 7. 45-7. 35 (m, 5H), 7.25 (dd, 1 H), 7.1 (dd, 1 H), 6.80 (t, 1 H), 6.5 (s, 1H), 4.7 (d, 2H), 3.75 (bs, 2H), 3.35 (bs, 2H), 2.4 (bs, 2H), 2.3 (s, 3H), 2.2 (bs, 2H).

Example 496 : 1H NMR (CDC13) # 7.95 (s, 1H), 7.9 (dt, 1H), 7.8 (t, 1H), 7.7 (d, 2H), 7.15 (m, 4H), 7.05 (dd, 1H), 6.9 (dd, 1H), 6.2 (s, 1H), 4.5 (d, 2H), 3.6 (t, 2H), 3.3 (dt, 2H).

Example 497 : 1H NMR (CH30D) 8 8.1 (s, 1 H), 7.9 (dt, 1 H), 7. 8 (d, 2H), 7.5 (d, 2H), 7.4 (m, 1 H), 7.3 (dd, 1 H), 7.2 (dd, 1 H), 6.4 (s, 1 H), 4.7 (d, 2H), 3.5 (t, 2H), 2.7 (m, 2H), 2.6 (bs, 4H), 1.8 (bs, 4H).

Example 498: 1H NMR (CDC13) 8 8.5 (t, 1H), 8.15 (dt, 1H), 8.0 (s, 1H), 7. 8 (d, 2H), 7.4 (d, 2H), 7.35 (m, 1 H), 7.25 (dd, 1 H), 7.15 (dd, 1H), 6.8 (t, 1H), 6.5 (s, 1 H), 4.7 (d, 2H), 3.7-2. 5 (m, 4H), 2.35 (s, 3H), 2.2 (m, 1 H), 1.9-1. 6 (m, 6H).

Example 499 : 1H NMR (CDCI3) 8 8.15 (dt, 1H), 8.0 (s, 1H), 7.8 (d, 2H), 7.4 (d, 2H), 7.35 (m, 1H), 7.25 (dd, 1H), 7.15 (dd, 1H), 6. 8 (t, 1H), 6.5 (s, 1H), 4.7 (d, 2H), 3.7 (m, 4H), 3.5 (dt, 2H), 2.6 (t, 2H), 2.5 (m, 4H).

Example 500 : 1H NMR (CH30D) # 8.15 (s, 1H), 7.9 (dt, 1H), 7.8 (d, 2H), 7.45 (d, 2H), 7.4 (m, 1H), 7.25 (dd, 1H), 7.15 (dd, 1H), 6.4 (s, 1H), 4.75 (d, 2H), 4.2 (m, 1 H), 3.4-2. 8 (m, 7H), 1.9-1. 6 (m, 4H).

Example 501: 1H NMR (CDCl3) 8 8.05 (dt, 1H), 8.0 (s, 1H), 7.6 (d, 2H), 7.4 (s, 1 H), 7.35 (d, 2H), 7.25 (dd, 1 H), 7.1 (dd, 1 H), 6.9 (t, 1 H), 6.5 (s, 1 H), 6.4 (t, 1 H), 4.7 (d, 2H), 4.2 (d, 2H), 2.3 (bs, 1 H).

Example 502: 1H NMR (CDCl3) 8 8.15 (dt, 1H), 8.0 (s, 1H), 7.75 (d, 2H), 7.45 (s, 1H), 7.4 (d, 2H), 7.3 (dd, 1H), 7.1 (dd, 1H), 6.8 (t, 1H), 6.5 (s, 1H), 6.1 (bs, 1H), 4.7 (d, 2H), 3.5 (dq, 2H), 1.2 (t, 3H).

Example 503 : 1H NMR (CDCl3) # 8.15 (dt, 1H), 8.0 (s, 1H), 7.8 (d, 2H), 7.4 (d, 2H), 7.35 (m, 1H), 7.25 (dd, 1H), 7.15 (dd, 1H), 6.9 (t, 1H), 6.5 (s, 1H), 6.4 (t, 1H), 4.75 (d, 2H), 4.1 (m, 2H).

Example 504 : 1H NMR (CDCl3) # 8.15 (dt, 1H), 8.0 (s, 1H), 7.8 (d, 2H), 7.45 (d, 2H), 7.4 (m, 1H), 7.25 (dd, 1H), 7.1 (dd, 1H), 6.8 (t, 1H), 6.6 (t, 1H), 6.5 (s, 1H), 4.7 (d, 1 H), 3.6 (m, 2H), 2.8 (t, 2H), 2.6 (q, 2H), 1.3 (t, 3H).

Example 505 : 1H NMR (CDCI3) s 8.15 (dt, 1H), 8.0 (s, 1H), 7.4 (m, 1H), 7.25 (dd, 1H), 7.15 (dd, 1H), 7.0 (t, 1H), 6.5 (s, 1H), 3.8 (m, 2H), 2.7 (t, 2H), 3.0 (d, 3H).

Example 506: 1H NMR (CDC13) 8 8.15 (dt, 1H), 8.0 (s, 1H), 7.4 (m, 1H), 7.25 (dd, 1H), 7.15 (dd, 1H), 7.0 (t, 1H), 6.5 (s, 1H), 3.8 (m, 2H), 3.6 (m, 6H), 3.4 (m, 2H), 2.7 (t, 2H).

Example 507 : 1H NMR (CDCI3) 8 8.15 (dt, 1H), 8.0 (s, 1H), 7.4 (m, 1H), 7.25 (dd, 1H), 7.15 (dd, 1H), 7.0 (t, 1H), 6.5 (s, 1H), 3.9 (t, 2H), 3.8 (dt, 2H), 3.7 (t, 2H), 2.7 (t, 2H), 2.6 (m, 4H).

Example 508 :'H NMR (CH30D) 8 8.1 (s, 1 H), 7.95 (dt, 1 H), 7.5 (m, 1 H), 7.35- 7.2 (m, 2H), 6.5 (s, 1 H), 3.6 (m, 4H), 3.25 (m, 4H), 2.4 (t, 2H), 2.05 (dt, 2H).

EXAMPLE 509: A solution of NaOH (59 mg, 1.47 mmol) in 1 mL of water was added to a suspension of NH2OH. HCI (102 mg, 1.47 mmol) in 10 mL of methanol at 0 °C.

After 5 min, the compound prepared in Example 210.10 (208 mg, 0.49 mmol) was added and the reaction mixture was refluxed overnight. The solvent was removed in vacuo and the residue was partitioned between water and EtOAc.

The EtOAc layer was dried (Na2SO4) and the solvent was evaporated. The resulting crude amidoxime was suspended in trimethyl orthoformate containing catalytic amount of PTS acid and refluxed overnight. The solvent was removed and the residue was taken up in EtOAc. The EtOAc layer was washed with aq NaHC03 followed by water and brine. The solvent was evaporated and the residue was purified by chromatography (silica, hexane: EtOAc (1: 1) ) to provide

80 mg (35%) of the oxadiazole.'H NMR (CDCI3) 8 8. 75 (s, 1 H), 8.20-8. 10 (m, 3H), 8.03 (s, 1 H), 7.53 (d, J = 9 Hz, 2H), 7.45-7. 36 (m, 1 H), 7.30-7. 22 (m, 2H), 7.16-7. 08 (m, 1H), 6.80 (t, J = 5 Hz, 1H), 6.56 (s, 1H).

LCMS: MH+ = 465.2 Example 510:

By essentially the same procedure set forth in Example 509 only substituting the compound prepared in Preparative Example 192, the above compound was prepared. yield = 75; MH+ = 453; m. p. = 79. 3°C.

EXAMPLE 511: F Bu bu /F \ N'/ I N Br N-N N 1) Me3SnN3 HN NON Toluene, reflux HN 2) Methanolic HCI N NAN % % I CN N-NH

A mixture of the nitrile (235 mg, 0.56 mmol) and Me3SnN3 (343 mg, 1.67 mmol) in 20 mL of dry toluene was refluxed for 2 days under Ar. The solvent was removed in vacuo and the residue was dissolved in dry methanol. HCI gas was bubbled through the solution for 15 min and the reaction mixture allowed to stand at overnight at RT. The next day, the solvent was removed, the residue was taken in water and the pH was adjusted to 5. The precipitated product was

extracted into EtOAc. Evaporation of the EtOAc layer after drying (Na2SO4) provided the residue which was purified by chromatography (silica, DCM: MeOH (98 : 2#95 : 5) ) to yield 50 mg (19%) of the pure tetrazole.'H NMR (CD30D) 8 8.10 (s, 1H), 8.00 (d, J = 9 Hz, 2H), 7.90 (t, J = 7 Hz, 1H), 7.65 (d, J = 9 Hz, 2H), 7.50-7. 40 (m, 1H), 7.30-7. 10 (m, 2H), 6.45 (s, 1H), 4.80 (s, 2H) ; LCMS : MH+ = 465.0 EXAMPLE 512:

By essentially the same procedure set forth in Example 511 only substituting the compound prepared in Example 192, the above compound was prepared. Yield = 64; MH+ = 453; m. p. = 238. 9°C.

EXAMPLE 513:

The compound prepared in Example 157 was dissolved in dioxane (30 mL) and a HCI-dioxane solution (4 M, 30 mL) was added. The reaction mixture was stirred at room temperature for 4 h. The reaction mixture was evaporated under reduced pressure and ethyl acetate (200 mL) was added. The organic

solution was washed with 1 N sodium hydroxide followed by saturated brine. The organic layer was dried over anhydrous sodium sulfate and evaporated under reduced pressure. Mu+ = 442. 1 EXAMPLE 514-526: By essentially the same procedure set forth in Example 513, only substituting the compounds shown in Column 2 of Table 41, the compounds shown in Column 3 of Table 41 were prepared.

TABLE 41 Ex. Column 2 Column 3 CMPD 514 __ \ M H+ _ N N 420. 1 or N-N Cil N-N HN 0 HN Ho 0 H N koj< NH rN-0- rNH 515riR''7R, MH= 515 A > MH+ T T 515 N 442. 1 Cl N_N Cl N-N Cl Cl 0 O ho han H N N 380. 1 Cl Cl HO HAN J H H 517 Br N N 406. 1 N Y-N o 'V" HNGNXOX HN xNH 518 w fT YY N Br N Br 380. 1 Cl N_N Cl N-N HN H HN Of NH2 T ruz o' N N 394. 1 NON Cl Cl O NEZ NH2 HN. HN. "1 0. Y H H 520 Br Br N N 366 N Cl YN_N Cl YN_N HN HN N O'\ H 521 Br Br MH" 521 I Br (\ Br 394 N /N or N-N ci N-N HN H c'N a LN H C'N (O$ H3C' N0. NH O 0 522 MH" _ 522 N 408. 1 Cl Cl ci N-N ci N-N HN HN 0 NO'\ H CH3 CH3 523 Br Br N 420. 1 -TU CI N Cl HN HN HOHL HN I I HO H 0 /N'//N'/ Y T Cul c 11 N-N ci N-N H HN I I OUZO 525-Br Br MH+ 420. 1 N-TU CL nu nu Cl ouzo HN HN 526 Br Br MH+ = /N Br I/N Br 428. 1 ci N-N ci N-N HN HN Cl N_N HN \/O ONH Ba r N N-N ci !) '' N Ci H. N to NH

EXAMPLES 528-564: General procedure for 5-piperidinyl parallel library formation: To a mixture of the starting material (80 mg, 0.21 mmol) shown in Column 2 of Table 42 in anhydrous CHzCtz (1. 5 mL) was added DIPEA (75 pL, 0.42 mmol) and the appropriate capping reagent (1.1 equiv. , 0.23 mmol). After 1 to 2 h, the reaction mixture was applied to 1000 micron preparatory TLC plate and was subsequently developed using a 8-10 % EtOH-CH2CI2 as eluent to afford the compounds shown in Column 3 of Table 42.

TABLE 42 | Ex. | Column 2 | Column 3 CMPD 528 HN Br CN MH+ = /I p 608 w ! H N Br 230. 1 °C Nu $ fNH NH 02CH3 02CL3 529 HN Br CN Yield N 0 82 w MH+= H Br 614 NH M. P. N-N 235. 4 OC N NH zu N S-N fez S-N 530 HN II L JL N 7 -m"-t) \ 486 530 N Br 486 N m. p. = N-N 60. 5 OC NH N-N n A N N 531 HN) Br ? MH'= N NN Br 500 m. p. _ X, I tNH < NH N-N NH Nazi N 532 HCI N H2NN 430 m. p. _ mlz r'" NH N N 533 N,, ( i I p 531 N 0 531 o w NN m. p. N-NN Br =1 05. 9 N H NA oc w N, N ßN nu N-N ZON N 534 Br MH+ HN N 0y 486 d WN_N Br NU I N-N /I W N_ N NH /ICI N 535 Br 0 MH+ HN N 00 500 yin Bu Nu NH N I I tN NH kan N NU \ N 536 Br O, NH2 430 HN N\ bu NN N-N Xt f /I NH ZON /1 N 537 Br Br NCunn MH = HN N 531 / L M ! NH N-N 0y NH N Ber Bu nu N nu /1 I I N 538 Br Br MH+ _ 486 N L N-N N N-N 69. 6 OC 0 N-N NU NU IN IL -N N 539 Br Br MH+ N N 500 'N' vil o N, N ^NO N, N 82. 3 C NHNOJ NH /II/II Nz Br Br MH+ N N 430 m, p. o NH QN S 22m39p6°O=C NH NH I I W N W N 541 Br Br MH+ N N 531 N N P. X 118. 1 °C NC N O NH H NH zizi N N 542 HN Br 0 MH+ = N 455 N N Br m. p. = N N-N N 109- 110 °C NH N-N NH N N N, N AN 429 N 543 HN Br MH+ _ 429 N YNHN-N X 111. 5 °C NH N-N NH I N, I I N 544 H MH+ N Po 455 Br N N ber tN dNH , nu ICI nu N N 545 H MH+ 429 Br N N Br N-N N NU NH N N I I 546 Br Br MH+ N N 455 ) 47 NH Ç $r 429 N N M. p. N, N 0 N, N NH 'NH y 0 y IN ICI N N 547 Br Br MH+ y NN O y N, N 64. 7 C nu nu /II/II N zon 548 494 Br m Pa- N-N N 76. 5 OC NU w N, N /nu NH N-N NH lui \ N 549 HN Br MH+ N 493 M. P. 0 N 8r m. p. o= N-N 0 N Br 83. 6 OC NU NON NH N N II 550 HN $r m. p. N N 465 Br M. p. \ NN =207. 5 ß NH N oc N-/ KAN W N I I f Br 0=S=0 N tN 551 f ! Br 494 N N BER Bu NU KAN N N I I 552 H MH+ N y 493 N'l N Ber N N tN tNH , I NH N N I I N 553 H MH+ O=S=O 465 Bu in i Br N-N N N_N ßN dNH NH N I I ZON ii N 554 H MH+ N 0=S=0 481 Bu I Br 102. 7 OC N ßNso-gN N NH N-N NH ici+ '0- W nô 555 Br Br MFi+ _ N N 494 m. p. = N N M. P. yin H I Nz 556 N N 493 H N i N m. P. _ N'/89. 1 °C N O=S=0 \ N, N NH NH I I N N 557 Br Br MH+ N N 465 H N N 'l m. P. _ N N M. P. HAN w N ) =S 558 HN Br NH Yield = tuant. H Br MH+ N-N N 443 NH N-M. P. NH \ N'N> 98. 3 OC NH (HCI salt) N, N zon 559 HN Br--N. CN MH+ _ nu \ N, H2N N Br N N NH NN nu N N il N N 560 HN Br NH Yield = tuant. H2N N Br MH+ N-N N 429 NH N-M. P. N 111. 5- NH 112. 6 oc N N N N N 460 460 N N '/m. P. _ zon YN_N N4S SN-N 122. 7 OC N S gNH H NH /, I N N 562 HN Br B, MHf = Il 460 N wNN Br m. P. _ '/H N o YNHN-N 94 95. 4 °C t ! jH N N'N NH N w N, N 563 H MH+ N Br SqzNH 460 Bu N Br NH N-N N NH N-N NU rii N

564 H S MH+ _ 460 Br N N Br m. p. _ (H 95. 4 °C i l NN NH NH /1 I IN IN Additional data for select examples given below.

Example 534: 1H NMR (300MHz, CDC13) s 8. 66-8. 62 (s, 1 H), 8.62-8. 58 (d, 1 H), 7.95 (s, 1 H), 7.72-7. 68 (d, 1 H), 7.36-7. 31 (dd, 1 H), 6.66-6. 62 (t, 1 H), 5.93 (s, 1 H), 4.65-4. 62 (d, 2H), 3.86-3. 82 (d, 1 H), 3.65-3. 58 (m, 1 H), 3.26- 3.12 (dd, 4H), 3.02-2. 80 (m, 3H), 2.10-2. 00 (m, 1 H), 1.67-1. 57 (m, 3H).

Example 535 : H NMR (300MHz, CDC13) 8 8.66-8. 62 (s, 1 H), 8.62-8. 58 (d, 1 H), 7.95 (s, 1 H), 7.72-7. 67 (d, 1 H), 7.36-7. 30 (dd, 1 H), 6.70-6. 64 (t, 1 H), 5.90 (s, 1 H), 4.63-4. 61 (d, 2H), 3.93-3. 86 (m, 1 H), 3.69-3. 61 (m, 4H), 3.27- 3.23 (m, 4H), 3.10-3. 01 (dd, 1 H), 2.93-2. 84 (m, 2H), 2.08-2. 03 (m, 1 H), 1.90-1. 57 (m, 4H).

Example 536: 1H NMR (300MHz, CDCI3) 8 8.67 (s, 1 H), 8.62-8. 58 (d, 1 H), 7.96 (s, 1 H), 7.72-7. 68 (d, 1 H), 7.36-7. 30 (dd, 1 H), 6.79-6. 72 (t, 1 H), 5.96 (s, 1 H), 4.86 (br s, 2H), 4.66-4. 63 (d, 2H), 3.89-3. 73 (m, 2H), 3.55-3. 32 (m, 2H), 3.00-2. 89 (m, 1H), 2.10-1. 97 (m, 2H), 1.70-1. 53 (m, 2H).

Example 537 : H NMR (300MHz, CDCI3) 8 8.66 (s, 1 H), 8.62-8. 58 (d, 1 H), 7.98 (s, 1 H), 7.77-7. 76 (t, 1 H), 7.72-7. 69 (d, 1 H), 7.63-7. 59 (m, 1 H), 7.56 (s, 1 H), 7.36-7. 29 (dd, 1 H), 6. 83-6. 79 (t, 1 H), 5.96 (s, 1 H), 4.67-4. 64 (d, 2H), 3.98-3. 93 (dd, 1 H), 3.. 79-3.68 (m, 2H), 3.37-3. 28 (m, 1 H), 3.03-2. 94 (m, 1 H), 2.12-1. 99 (m, 1 H), 1.76-1. 56 (m, 3H).

Example 544 : H NMR (300MHz, CDC13) 8 8.66-8. 62 (d, 1 H), 8.61-8. 58 (dd, 1 H), 7.95 (s, 1 H), 7.72-7. 67 (d, 1 H), 7. 36-7. 30 (dd, 1 H), 6. 80-6. 62 (br s, 1 H), 5.88 (s, 1 H), 4.63 (s, 2H), 3.08-2. 95 (m, 2H), 2.87-2. 80 (m, 2H), 2. 04 (m,

1 H), 1.85-1. 78 (m, 4H), 1.52-1. 44 (m, 1 H), 0.87-0. 82 (m, 2H), 0.72-0. 66 (m, 2H).

Example 545 : H NMR (300MHz, CDCI3) 8 8.66 (s, 1 H), 8.62-8. 58 (br t, 1 H), 7.97 (s, 1 H), 7.73-7. 68 (d, 1 H), 7.36-7. 30 (br t, 1 H), 6.79-6. 72 (br t, 1 H), 5.96 (s, 1 H), 4.64 (br s, 2H), 4.59-4. 46 (br d, 1 H), 3.95-3. 74 (br m, 1 H), 3.57 - 3. 49 (dd, 1 H), 3.10-3. 01 (dd, 1 H), 2.86-2. 70 (m, 2H), 2.13 (s, 3H), 2.06- 2.00 (m, 2H), 1.65-1. 48 (m, 2H).

Example 551: 1H NMR (300MHz, CDCI3) 8 8.67 (s, 1 H), 8.63-8. 59 (d, 1 H), 7.96 (s, 1 H), 7.74-7. 69 (d, 1 H), 7.36-7. 30 (dd, 1 H), 6.69-6. 64 (t, 1 H), 5.95 (s, 1 H), 4.67-4. 63 (d, 2H), 3.85 3.65 (m, 1 H), 3.75-3. 65 (m, 1 H), 3.25-3. 18 (dd, 1 H), 3.03-2. 90 (m, 2H), 2.81 (s, 6H), 2.03-1. 95 (m, 1 H), 1. 89-1. 68 (m, 3H).

Example 552: 1H NMR (300MHz, CDCI3) 8 8.67 (s, 1 H), 8.62-8. 59 (d, 1 H), 7.95 (s, 1 H), 7.74-7. 69 (d, 1 H), 7. 36-7. 31 (dd, 1 H), 6.67-6. 60 (t, 1 H), 5.98 (s, 1 H), 4.67-4. 63 (d, 2H), 3.92-3. 86 (m, 1 H), 3.85-3. 75 (m, 1 H), 3.40-3. 30 (dd, 1 H), 3.27-3. 16 (m, 1 H), 3.10-2. 86 (m, 2H), 2.10-1. 78 (m, 3H), 1.40- 1.30 (d, 6H).

Example 553 : H NMR (300MHz, CDCI3) 8 8. 67 (s, 1 H), 8.62 (br s, 1 H), 7.96 (s, 1 H), 7.74-7. 69 (d, 1 H), 7.36-7. 31 (dd, 1 H), 6. 70-6. 66 (t, 1 H), 5.98 (s, 1 H), 4.67-4. 63 (d, 2H), 3.88-3. 81 (m, 1 H), 3.71-3. 65 (m, 1 H), 3.20-3. 11 (dd, 1 H), 3.02-2. 91 (m, 1 H), 2.90-2. 80 (m, 4H), 2.01-1. 80 (m, 3H).

Example 559 :'H NMR (300MHz, CDCI3) 8 8.66-8. 60 (d, 1 H), 8. 50-8. 44 (dd, 1 H), 8.01 (s, 1 H), 7.93 (m, 1 H), 7. 48-7. 40 (dd, 1 H), 6.08 (s, 1 H), 4.80-7. 74 (s, 2H), 4. 32-4. 19 (br d, 2H), 3.10-2. 86 (m, 2H), 1.95-1. 68 (m, 4H).

Example 563 : H NMR (300MHz, CDC ! s) 8 8.66 (s, 1 H), 8.62-8. 58 (d, 1 H), 7.96 (s, 1 H), 7.73-7. 68 (d, 1 H), 7.36-7. 30 (dd, 1 H), 6.96-6. 86 (br s, 1 H), 6.79-6. 74 (t, 1 H), 6.00 (s, 1 H), 4.67-4. 64 (d, 2H), 4.37-4. 30 (dd, 1 H), 4.22- 4.13 (m, 1H), 3.97-3. 86 (dd, 1 H), 3.73-3. 64 (m, 1H), 3.17-3. 14 (d, 3H), 3.07 - 2. 99 (m, 1 H), 2.20-1. 97 (m, 2H), 1.68-1. 48 (m, 2H).

GENERAL PROCEDURE 1: Procedure for the amide formation parallel synthesis: 0 0 HN Br 1) R'C02H, HOBt P-EDC resin %"N) 4 \ NN ) I HN p-NCO resin N-N HN P-NCO resin HN N N

Parallel synthesis was conducted in polypropylene 96-well reaction blocks with removable top seal and fixed bottom seal. Each reaction well was fitted with a 20 micron polypropylene bottom frit and the maximum volume was 3 mL.

Collection block was not fitted with bottom frit. To each reaction well was added a solution of an amine (0. 021 mmol) dissolved in a DMF-THF-MeCN mixture (4: 3: 3 v/v, 0.95 mL), EDC resin (P-EDC, Polymer Laboratories Ltd. , 43 mg, 0.063 mmol), 1-hydroxybenzotriazole (HOBt, 5.67 mg, 0.042 mmol) and a solution of a carboxylic acid in dimethylformamide (1 M, 0.0315 mL, 0.0315 mmol). The reaction mixture was agitated at room temperature for 16 h. The crude product solution was filtered into a reaction well loaded with trisamine resin (P-NH2, Argonaut Tech. Inc., 30 mg, 0.126 mmol) and isocyanate resin (P- NCO, Argonaut Tech. Inc., 35 mg, 0.063 mmol). The reaction mixture was agitated at room temperature for 16 h and filtered into the collection block. The product solution was evaporated under reduced pressure to afford the desired amide product.

GENERAL PROCEDURE 2: Procedure for the sulfonamide formation parallel synthesis R\ O HN N Br 1) R'SOaCI SN Br P-DIEA resin N NN _ 2) P-NH2 resin N-N, HN P-NCO resin HN \ nazi N I

Parallel synthesis was conducted in polypropylene 96-well reaction blocks with removable top seal and fixed bottom seal. Each reaction well was fitted with a 20 micron polypropylene bottom frit and the maximum volume was 3 mL.

Collection block was not fitted with bottom frit. To each reaction well was added a solution of an amine (0. 021 mmol) dissolved in a DMF-THF-MeCN mixture (3: 2: 2 v/v, 0.95 mL), DIEA resin (P-DIEA, Argonaut Tech. Inc., 18 mg, 0.063 mmol) and a solution of a sulfonyl chloride in dimethylformamide (1 M, 0.0315 mL, 0.0315 mmol). The reaction mixture was agitated at room temperature for 16 h. The crude product solution was filtered into a reaction well loaded with trisamine resin (P-NH2, Argonaut Tech. Inc., 30 mg, 0.126 mmol) and isocyanate resin (P-NCO, Argonaut Tech. Inc., 35 mg, 0.063 mmol). The reaction mixture was agitated at room temperature for 16 h and filtered into the collection block. The product solution was evaporated under reduced pressure to afford the desired sulfonamide product.

GENERAL PROCEDURE 3: Procedure for the urea formation parallel synthesis 0 HN Br R'w 1) R'NCO H N Br zon N 2) P-NH resin ) 2 NN HN P-NCO resin HN HN w N \ N Parallel synthesis was conducted in polypropylene 96-well reaction blocks with removable top seal and fixed bottom seal. Each reaction well was fitted with

a 20 micron polypropylene bottom frit and the maximum volume was 3 mL.

Collection block was not fitted with bottom frit. To each reaction well was added a solution of an amine (0.021 mmol) dissolved in a DMF-MeCN mixture (1: 1 v/v, 0.95 mL) and a solution of an isocyanate in dichloromethane (0.33 M, 0.126 mL, 0.042 mmol). The reaction mixture was agitated at room temperature for 16 h.

The crude product solution was filtered into a reaction well loaded with trisamine resin (P-NH2, Argonaut Tech. Inc., 30 mg, 0.126 mmol) and isocyanate resin (P- NCO, Argonaut Tech. Inc., 35 mg, 0.063 mmol). The reaction mixture was agitated at room temperature for 16 h and filtered into the collection block. The product solution was evaporated under reduced pressure to afford the desired urea product.

GENERAL PROCEDURE 4: Procedure for the reductive alkylation parallel synthesis R' HN Br 1) R'R"CO R"1N Br Me4NBH (OAc) 3 bd Nz N'N 2) P-S03H resin N, i HN 3) NH3-MeOH HN \ nazi N Parallel synthesis was conducted in polypropylene 96-well reaction blocks with removable top seal and fixed bottom seal. Each reaction well was fitted with a 20 micron polypropylene bottom frit and the maximum volume was 3 mL.

Collection block was not fitted with bottom frit. To each reaction well was added a solution of an amine (0.021 mmol) dissolved in AcOH-DCE mixture (1: 99 v/v, 0.5 mL), a solution of an aldehyde or ketone in dichloroethane (1 M, 0.147 mL, 0.147 mmol), and a solution of tetramethylammonium triacetoxyborohydride (11 mg, 0.042 mmol) dissolved in AcOH-DCE mixture 1: 99 v/v, 0.5 mL). The reaction mixture was agitated at room temperature for 3 days. The crude product solution was filtered into a reaction well loaded with sulfonic acid resin Lanterns (P-SO3H, MimotopesPty Ltd. , 0.3 mmol). The reaction mixture was agitated at room temperature for. 2 h and decanted. The product resin Lanterns

were washed with methanol (1 mL) for three times. A solution of ammonia in methanol (2 M, 1.2 mL) was added. The reaction mixture was agitated at room temperature for 30 min. and filtered into the collection block. The product solution was evaporated under reduced pressure to afford the desired tertiary amine product.

GENERAL PROCEDURE 5: Procedure for the parallel synthesis of 7, N- substituted pyrazol [1,5a] pyrimidines To 3-bromo-7-chloro-5- (2-chloro-phenyl)-pyrazolo [1,5-a] pyrimidine (9.0 mg, 0.03 mmol) in tetrahydrofuran were added di-iso-propylethylamine (12 p. L, 0.07), followed by cyclopropylmethylamine (70 jus,. 07 mmol ; 1 M solution in DMF). The reaction mixture was heated to 70 °C for 36 h and then cooled to rt.

The mixture was treated with (P-NCO, Argonaut Tech. Inc 70 mg, 0.12 mmol), and P-C03 (Argonaut Tech. Inc 70 mg, 0.24 mmol) and shaken at rt for 12-18 h.

The solution was filtered and evaporated to dryness to provide the product. observed m/z 375.21.

GENERAL PROCEDURE 6: Procedure for the parallel synthesis of 5, N- substituted pyrazolo [1, 5a] pyrimidines General protocols : Parallel synthesis was performed in a 96 well polypropylene blocks as described elsewhere. In the instance that heating was required, reactions were conducted in 2.5 mL glass tubes individually sealed with a polypropylene mat and heating achieved by a 96 well heat transfer block. Br H Br NIN NON STEP A SN N NO\/STEP B N'H N3 Nb

STEP A: To the 3-bromo-5-chloro-7-N-Boc-alkylamino-pyrazolo [1, 5-a] pyrimidine (17 mg, 0.04 mmol) in p-dioxane were added DIEA (9 pL, 0.05), followed by cyclopropyl-methylamine (80 p1L,. 08 mmol ; 1M solution in isopropanol). The reaction mixture was heated to 90 °C for 36 h and then cooled to rt. The mixture was treated with P-NCO (Argonaut Tech. Inc. 70 mg, 0.12 mmol) and P-C03 (Argonaut Tech. Inc. 70 mg, 0.24 mmol) and shaken at rt for 12-18 h. The solution was filtered and evaporated to dryness to provide the product.

STEP B (acidic) : The product from STEP A was taken up in 35% TFA/DCM and agitated for 4 h followed by concentration under high vacuum. The residue was treated with 10% HCI (aq) in MeOH agitated for 2 h and then concentrated to give the desired product.. observed m/z 375.21.

STEP B (basic) : The product from step A was taken up in EtOH and treated with Ambersep'§'900-OH ion exchange resin (Acros, 100mg), heated at reflux for 48 h with gently stirring. The reaction mixture was cooled to rt, filtered and concentrated to provide the desired product.

EXAMPLE 565: By utilizing the procedure set forth in General Procedure 1 and the compound from Example 462 shown below, the compounds with the observed m/z shown in Table 43 were prepared.

EXAMPLE 566: By utilizing the procedure set forth in General Procedure 1 and the compound from Example 471 shown below, the compounds shown in Table 44 with the observed m/z were prepared.

EXAMPLE 567: By utilizing the procedure set forth in General Procedure 1 and the compound from Example 515 shown below, the compounds shown in Table 45 with the observed m/z were prepared.

EXAMPLE 568: By utilizing the procedure set forth in General Procedure 1 and the compound from Example 513 shown below, the compounds shown in Table 46 with the observed m/z were prepared.

EXAMPLE 569: By utilizing the procedure set forth in General Procedure 1 and the compound from Example 526 shown below, the compounds shown in Table 47 with the observed m/z were prepared.

EXAMPLE 570: By utilizing the procedure set forth in General Procedure 1 and the compound from Example 524 shown below, the compounds shown in Table 48 with the observed m/z were prepared.

EXAMPLE 571: By utilizing the procedure set forth in General Procedure 1 and the compound from Example 525 shown below, the compounds shown in Table 49 with the observed m/z were prepared.

EXAMPLE 572: By utilizing the procedure set forth in General Procedure. 1 and the compound from Example 526.10 shown below, the compounds shown in Table 50 with the observed m/z were prepared.

EXAMPLE 573: By utilizing the procedure set forth in General Procedure 1 and the compound from Example 518 shown below, the compounds shown in Table 51 with the observed m/z were prepared.

EXAMPLE 574: By utilizing the procedure set forth in General Procedure 1 and the compound from Example 519 shown below, the compounds shown in Table 52 with the observed m/z were prepared.

EXAMPLE 575: By utilizing the procedure set forth in General Procedure 1 and the compound from Example 520 shown below, the compounds shown in Table 53 with the observed m/z were prepared.

EXAMPLE 576: By utilizing the procedure set forth in General Procedure 1 and the compound from Example 522 shown below, the compounds shown in Table 54 with the observed m/z were prepared.

EXAMPLE 577: By utilizing the procedure set forth in General Procedure 1 and the compound from Example 523 shown below, the compounds shown in Table 55 with the observed m/z were prepared.

EXAMPLE 578 : By utilizing the procedure set forth in General Procedure 2 and the compound from Example 462 shown below, the compounds shown in Table 56 with the observed m/z were prepared.

EXAMPLE 579: By utilizing the procedure set forth in General Procedure 2 and the compound from Example 471 shown below, the compounds shown in Table 57 with the observed m/z were prepared.

EXAMPLE 580: By utilizing the procedure set forth in General Procedure 2 and the compound from Example 515 shown below, the compounds shown in Table 58 with the observed m/z were prepared.

EXAMPLE 581: By utilizing the procedure set forth in General Procedure 2 and the compound from Example 513 shown below, the compounds shown in Table 59 with the observed m/z were prepared.

EXAMPLE 582: By utilizing the procedure set forth in General Procedure 2 and the compound from Example 513 shown below, the compounds shown in Table 60 with the observed m/z were prepared.

EXAMPLE 583: By utilizing the procedure set forth in General Procedure 2 and the compound from Example 524 shown below, the compounds shown in Table 61 with the observed m/z were prepared.

EXAMPLE 584: By utilizing the procedure set forth in General Procedure 2 and the compound from Example 525 shown below, the compounds shown in Table 62 with the observed m/z were prepared.

EXAMPLE 585: By utilizing the procedure set forth in General Procedure 2 and the compound from Example 526.10 shown below, the compounds shown in Table 63 with the observed m/z were prepared.

EXAMPLE 586: By utilizing the procedure set forth in General Procedure 2 and the compound from Example 518 shown below, the compounds shown in Table 64 with the observed m/z were prepared.

EXAMPLE 587: By utilizing the procedure set forth in General Procedure 2 and the compound from Example 519 shown below, the compounds shown in Table 65 with the observed m/z were prepared.

EXAMPLE 588: By utilizing the procedure set forth in General Procedure 2 and the compound from Example 520 shown below, the compounds shown in Table 67 with the observed m/z were prepared.

EXAMPLE 589: By utilizing the procedure set forth in General Procedure 2 and the compound from Example 521 shown below, the compounds shown in Table 68 with the observed m/z were prepared.

EXAMPLE 590: By utilizing the procedure set forth in General Procedure 2 and the compound from Example 523 shown below, the compounds shown in Table 69 with the observed m/z were prepared.

EXAMPLE 591: By utilizing the procedure set forth in General Procedure 3 and the compound from Example 462 shown below, the compounds shown in Table 70 with the observed m/z were prepared.

EXAMPLE 592: By utilizing the procedure set forth in General Procedure 3 and the compound from Example 471 shown below, the compounds shown in Table 71 with the observed m/z were prepared.

EXAMPLE 593: By utilizing the procedure set forth in General Procedure 3 and the compound from Example 513 shown below, the compounds shown in Table 72 with the observed m/z were prepared.

EXAMPLE 594: By utilizing the procedure set forth in General Procedure 3 and the compound from Example 524 shown below, the compounds shown in Table 73 with the observed m/z were prepared.

EXAMPLE 595: By utilizing the procedure set forth in General Procedure 3 and the compound from Example 524 shown below, the compounds shown in Table 74 with the observed m/z were prepared.

EXAMPLE 596: By utilizing the procedure set forth in General Procedure 3 and the compound from Example 519 shown below, the compounds shown in Table 75 with the observed m/z were prepared.

EXAMPLE 597: By utilizing the procedure set forth in General Procedure 3 and the compound from Example 520 shown below, the compounds shown in Table 76 with the observed m/z were prepared.

EXAMPLE 598: By utilizing the procedure set forth in General Procedure 3 and the compound from Example 521 shown below, the compounds shown in Table 77 with the observed m/z were prepared.

EXAMPLE 599: By utilizing the procedure set forth in General Procedure 3 and the compound from Example 523 shown below, the compounds shown in Table 78 with the observed m/z were prepared.

EXAMPLE 600: By utilizing the procedure set forth in General Procedure 4 and the compound from Example 462 shown below, the compounds shown in Table 79 with the observed m/z were prepared.

EXAMPLE 601: By utilizing the procedure set forth in General Procedure 4 and the compound from Example 471 shown below, the compounds shown in Table 80 with the observed m/z were prepared.

EXAMPLE 602: By utilizing the procedure set forth in General Procedure 4 and the compound from Example 525 shown below, the compounds shown in Table 81 with the observed m/z were prepared.

EXAMPLE 603: By utilizing the procedure set forth in General Procedure 4 and the compound from Example 526.10 shown below, the compounds shown in Table 82 with the observed m/z were prepared.

EXAMPLE 604: By utilizing the procedure set forth in General Procedure 4 and the compound from Example 521 shown below, the compounds shown in Table 83 with the observed m/z were prepared.

EXAMPLE 605: By utilizing the procedure set forth in General Procedure 4 and the compound from Example 523 shown below, the compounds shown in Table 84 with the observed m/z were prepared.

EXAMPLE 606: By utilizing the procedure set forth in General Procedure 5 and the compound from Preparative Example 81 shown below, the compounds shown in Table 85 with the observed m/z were prepared.

EXAMPLE 607: By utilizing the procedure set forth in General Procedure 6 and the compound from Preparative Example 196, the compounds shown in Table 86 with the observed m/z were prepared.

PREPARATIVE EXAMPLE 500

Piperidine-2-ethanol (127 g, 980 mmol) in 95% EtOH (260 mL) was added to (S)- (+)-camphorsulfonic acid (228.7 g, 1.0 eq. ) in 95% EtOH (150 mL) and the resulting solution was warmed to reflux. To the warm solution was added Et20 (600 mL) and the solution cooled to room temperature and let stand 3 days. The resulting crystals were filtered and dried in vacuo (25 g): mp 173-173 °C (lit. 168 °C). The salt was then dissolved in NaOH (3M, 100 mL) and stirred 2 hours and the resulting solution was extracted with CH2CI2 (5 x 100 mL). The combined organics were dried over Na2SO4, filtered, filtered and concentrated under reduced pressure to give (S)-piperidine-2-ethanol (7.8 g) a portion of which was recrystallized from Et20 : mp= 69-70 °C (lit. 68-69 °C) ; [a] p = 14. 09° (CHC13, c=0.2).

PREPARATIVE EXAMPLE 501 Bye essentially the same procedure set forth in Preparative Example 500 only substituting (R)- (-)-camphorsulfonic acid, (R)-piperidine-2-ethanol was prepared. (1.27 g) : [a] p = 11. 3° (CHCI3, c=0.2).

PREPARATIVE EXAMPLE 502 To pressure bottle charged with a solution of cis- (1 R, 2S)- (+)-2- (Benzylamino) cyclohexanemethanol (1g, 4.57 mmol) in MeOH (35 mL) was added 20% wt Pd (OH) 2 (0.3g, >50% wet) in one portion. The mixture was shaken under 50 psi of H2 in a Parr hydrogenation apparatus for 12 h. The

mixture was purged to N2 and was filtered through a pad of Celite. The pad was generously washed with MeOH (2 x 25 mL) and the resulting filtrate was concentrated under reduces pressure to afford 0.57g (97%) of a white solid.

M+H = 130.

PREPARATIVE EXAMPLE 503 Br Br CI N 4 STEP A N-N STEP B '\ N/ \ NN N Cl SMe H Br H Br N N) x N N stem C , O'- \ N O'-, OH SMe OH OH SMe H, S Step A: To a solution of 3-Br adduct (1.1 g, 4.1 mmol) from Preparative Example 142 in THF (40 mL) at 0 °C was added CH3SNa (0.32 g, 4.53 mmol) in one portion. The heterogenous mixture was stirred for 72 h at rt and the mixture was concentrated under reduced pressure. The crude product was partitioned between water (10 mL) and EtOAc (30 mL) and the layers were separated. The organic layer was washed with brine (1 x 10 mL) and dried (Na2SO4). The organic layer was filtered and concentrated under reduced pressure to afford 1.0 g (88%) of a yellow solid. mp 150-152 °C ; M+H = 280. This material was taken onto Step B without further purification.

Step B: To a solution of thiomethyl derivative (1.5 g, 5.37 mmol) from Step A in dioxane/DIPEA (15 mL/4 mL) at rt was added amino alcohol (1.3 g, 8.06 mmol) from Preparative Example 10. The mixture was heated at reflux for 48 h, cooled to rt, and concentrated under reduced pressure. The crude product was purified by flash chromatography using CH2CI2/MeOH (30: 1) as eluent to afford 1.8 g of product (90%) as a yellow crystalline solid. mp 167-169 °C ; M+H = 373.

Step C:

To a solution of thiomethyl derivative (2.2 g, 5.92 mmol) from Step B in CH2CI2 (20 mL) at 0 °C was added MCPBA (1.53 g, 8.9 mmol) in one portion.

The resulting mixture was stirred for 2h at 0 °C whereupon the mixture was diluted with CH2CI2 (20 mL) and sat. aq. NaHC03 (15 mL). The layers were separated and the organic layer was washed with sat. aq. NaHC03 (15 mL) and brine (1 x 15 mL). The organic layer was dried (Na2SO4), filtered, and concentrated under reduced pressure to afford 2.0 g of a brown solid (87%). mp 181-183 °C ; M+H = 388.

PREPARATIVE EXAMPLE 504 The title compound (racemic) was prepared according to the procedure set forth in Preparative Example 503 except substituting the commercially available cis-hydroxymethyl-1-cyclohexylamine hydrochloride in Step B.

PREPARATIVE EXAMPLE 505 Br CI STEP A STEP A N-N r N OH',, SE bu STEM B NN OH' 0 Step A: Treatment of thiomethyl derivative (2.0 g, 7.2 mmol) from Step A of Preparative Example 503 with (S)-piperidine-2-ethanol (1.2 g, 9.3 mmol) from Preparative Example 500 under the identical conditions as described in Step B of Preparative Example 503,0. 90 g (34%) of the title compound was prepared semisolid. mp 173-175 °C. M+H = 372.

Step B:

Following the procedure from Step C in Preparative Example 503, the thiomethyl derivative (0.30 g, 0. 81 mmol) was treated with MCPBA (0.21 g, 1.2 mmol) to afford 0.31 g (99%) the title compound as a yellow viscous oil. M+H = 388.

PREPARATIVE EXAMPLE 506 The title compound (racemic) was prepared according to the procedure set forth in Preparative Example 505 except substituting the commercially available piperidine-2-ethanol. M+H = 388.

PREPARATIVE EXAMPLE 507 t-BuOK (112. 0g, 1.00 mol) was stirred under N2 in dry Et20 (3.0 L) in a 5 L flask equipped with an addition funnel. A mixture of butyronitrile (69.0 g, 1.00 mol) and ethylformate (77.7 g, 1.05 mol) was added dropwise during 3 hrs, the reaction mixture was then stirred overnight at room temperature. The mixture was cooled to 0°C, AcOH (57 mL) was added, the mixture was filtered, and the solid was washed with Et20 (500 mL). The combined filtrates were evaporated at room temperature on a rotovap to give pale yellow oil (95. 1g).

The oil was dissolved in dry EtOH (100 mL), 99% hydrazine monohydrate (48 mL) was added, then AcOH (14 mL) was added, and the mixture was refluxed under N2 overnight. The solvents were evaporated and the resulting oil was chromatographed on silicagel with CH2CI2 : 7N NH3 in MeOH. 22.4 g (20%) of 3- amino-4-ethylpyrazole was obtained as clear oil that solidified upon standing.

PREPARATIVE EXAMPLE 508

Step A: The pyrazol from Preparative Example 507 (9.80g) and dimethylmalonate (45 mL) were stirred and refluxed under N2 for 3 hrs. The excess of dimethylmalonate was evaporated in a vacuum and the residue was chromatographed with 15: 1 CH2CI2 : MeOH to yield pale yellow solid (10.6 g, 57%). LCMS : MH+ = 212.

Step B: Dry MeOH (200 mL) was added under N2 to a mixture of the amide from Setp A (11. 9g, 56.4 mmol) and sodium methoxide (4.57g, 84.6 mmol). The mixture was stirred and refluxed under N2 for 5 hrs, cooled to rt, and conc. HCI (20 mL) was added. The solvents were evaporated and the residue was suspended in H20 (300 mL). The solid was filtered off, washed on filter with 2x300 mL of H20, and dried in a vacuum at 100°C. 7. 40g (73%) of cream- colored solid was obtained. LCMS: MH+ = 180.

Step C: H POCI3 CI N N N, N-dimethyl 0 aniline Cl POC13 (100 mL) and N, N-dimethylaniline (20 mL) were added under N2 to the diketone from Step B (7.70 g), and the mixture was stirred and refluxed for 20 hrs under N2. Then it was cooled to rt, carefully poured onto 1 L of crushed ice, and extracted with EtOAc (2x500 mL). The extracts were washed with H20 (500 mL), dried over Na2SO4, filtered, and the solvent was evaporated. The residue was chromatographed with CH2CI2 to yield pale yellow solid (8.20 g, 90%). LCMS: MH+ = 216.

PREPARATIVE EXAMPLE 508.10

By essentially the same procedure set forth in Preparative Example 508, only substituting the compound from Preparative Example 1, the above compound was prepared. LCMS: MH+ = 228.

PREPARATIVE EXAMPLE 509 A mixture of the dichloride from Preparative Example 508 (3. 13g, 14.5 mmol), the amine. HCl from Preparative Example (3. 00g, 18.9 mmol), DIPEA (7.5 mL), and dry NMP (40 mL) plus dry dioxane (40 mL) was stirred at 60°C for 4 days under N2. The solvents were then distilled off in a vacuum and the residue was chromatographed with 6: 1 EtOAc: MeOH and then rechromatographed with 12: 1 CH2CI2 : MeOH. So obtained solid was suspended in H20 (100 mL), filtered, washed on filter with H20 (2x100 mL), and dried in a vacuum. Pale rose solid (2. 37g, 54%) was obtained. M+H = 304.

Preparative Examples 510-516 By essentially the same procedure set forth in Preparative Example 509 only substituting the amines in Column 2 of Table 500 and the chlorides shown in Column 3 of Table 500, the compounds shown in Column 4 of Table 500 were prepared.

TABLE 500 Prep. Ex. Column 2 Column 3 Column 4 CMPD 510 NH3CI M+H = 316 Cl, N Cl N Cl N Vil ci han N +, 0- I I 512 NH2 M+H = 318 ci N Cl N (1. \ \ ci han N 0 N O 513 NH2 M+H = 318 CI N Cl N N, N-N N-N O C HN \I 0 0 514 gNH2 X \ CI N CI N NH2 ci N N non. NN N H2 515 NH2 M+H = 332 Cl N Cl N \ v Ci HN N 0 516P\"\ 516 NH2 CI N Cl N N'N N'N IN / N s

PREPARATIVE EXAMPLE 517: By essentially the same procedure set forth in Preparative Example 184 only substituting the amines in Column 2 of Table 501, the compounds shown in Column 3 of Table 501 were prepared.

TABLE 501 Prep. Ex. Column 2 Column 3 CMPD 518. NHZ Br M+H= Cri N 0 Y- Han HN irl HN I HN-IrA 519 NH2 Br Cl, N 6 vu HN HNNi 0 1 I 0

PREPARATIVE EXAMPLE 520-521: By essentially the same procedure set forth in Preparative Example 192 only substituting the compounds in Column 2 of Table 502, the compounds shown in Column 3 of Table 502 were prepared.

TABLE 502 Prep. Ex. Column 2 Column 3 CMPD 520 Br Br M+H= 522. 1 522. 1 HNt t0YN HN 0Y N H HN 0 0 521 Br Br M+H= ' < YN-N HN \/OUN HN YY ; t 0 HNt t0YNt Oj EXAMPLE 1000:

A mixture of the compound prepared in Preparative Example 509 (1.50 g, 4.94 mmol) with the aminoalcohol from Preparative Example 500 (1.91 g, 14.8 mmol) in dry NMP (3 mL) was stirred under N2 at 160°C for 48 hr. The NMP was distilled off in a vacuum and the residue was chromatographed first with 5: 1 EtOAc: MeOH, then the crude product was rechromatographed with 10: 1 CH2CI2 : MeOH. White solid (460 mg, 24%) was obtained. LCSM: MH+ = 397; mp = 113-115 °C.

EXAMPLE 1001: Major side product isolated (540 mg, 29%) was deoxygenated product (LCMS: MH = 381; mp = 49-52 °C :

EXAMPLES 1002-1014: By essentially the same procedure set forth in Example 1000 only substituting the amines in Column 2 of Table 1000 and the chlorides in Column 3 of Table 1000 the compounds in column 4 of Table 1000 were prepared.

TABLE 1000 Ex. | Column 2 Column 3 Column 4 CMPD 1002 ON H MH"409 ; ZON ru Cl N N-N mp = 165-171 N-N-Oc OU HN OH HN \ N ; _ N ; o- 1003,,, NH2 MH = 397 ; H CI N,. N N mp = 219-221 Oc OH N-N-N N HN OH HN o-N o- 1004 NH2 09-, 1004. NH2 MH+ = 409 ; CI N N mp = 138-142 oc HN OH HN HN. OHHN HN OH HN 1005 1005 MH = 411 ; N H CI N N N _ LAH C 194 196 i i P N N C OH HN OH HN Bzw N O N O 1006 NH2 H MH+ = 411 ; H Mp = 118-120 118 Oc OU HN OH HN N 0 N 0 1007 MH+ = 411 ; NH CI N m = 85 87 C i S YN N f YNuN OH HO OH HN Cl N N N O O 0 0 1008. NH2 MH+ = 411 ; N-Oc CI N,, N N m = 105-10 N N HN OH HN XI fuzz O p 0 0 1009 M H+ = 397 ; ONH Cl N ON N mP = 173-177 N-N N-N Oc i i N, N N, N °C OH HN OH HN r NtN I Nus nus 1010 NH2 H MH+ = 397 ; H Cl N N N mp = 169-173 N Oc OH N-N N HN OH HN I __"I NtN NtN NHs NH2 1011 MH+ = 425 NH CI N N N N, N NN OH HN OH HN Nz K k 1012 NH2 H MH+ 425 ; 1012.. NH2 MH-425 ; H mp = 232-234 Oc 0"/, N-N HN OH HN N HN OH HN a0 {N A O N 0 N 0 1013 ONH Cl N ON N XNoN C-XNsN OH HN OH HN /NJ/N 1014,,, NH2 H CI N,,, N N OH , N-N zz : -I N (N HN OH HN I /f EXAMPLE 1015 :

To a solution of sulfoxide from Preparative Example 505 (0.10 g, 0.28 mmol) in n-BuOH in a sealed tube was added Et3N (0.13 mL, 1.0 mmol) followed by the amine dihydrochloride (0.13 g, 0.65 mmol) from Preparative Example 216.

The tube was sealed and was heated to 100 °C, cooled to room temperature, and was concentrated under reduced pressure. The crude residue was purified by preparative TLC (6 x 1000 tM) eluting with CH2CI2/MeOH (20: 1) to afford 50 mg (40 %) of a pale white solid. mp 182-185 °C ; M+H = 446.

EXAMPLES 1016-1026: By essentially the same procedure set forth in Example 1015 only substituting the sulfoxide shown in Column 2 of Table 1001 and the amine in Column 3 of Table 1001, the compounds shown in Column 4 of Table 1001 were prepared.

TABLE 1001 Ex. Column 2 Column 3 I Column 4 CMPD 1016 Br NH3Ci mp = 182- I bar N N \ (/ N N 185 OC ; ruz \ N'' N NYN d N M+H = 448 OH oSuso NH2 OH HN I NON NH2 1017 n Br NH3CI n Br mp = 187- Br N N/N N 1 9 °C ; N, I N W \ NN M H = 445 OH oSsxo xNS OH HN Oh han N N N N 1018 Br NH2 Br mp = 139- 143 OC ; \ N l + _ S4 N M+H = 453 NU ZON AN NH2 1020 r Br NH3CI mp = 186- Bu O N 189 OC ; I g YN_N XN C XN_N/2 M+H = 485 N OH N N N 1021 H N"Br NH3CI H Br mp = 154- N N NtHN NU - nus) NON NH2 i. N OH HN Nu2 II NN NH2 1022 H N N Br NH3CI H Br mp = 103- ,,, N N 105 oc ; N\ i .., M+H-485 OHSub sN2N OH HNx N-IN N N N- 1023 H Br NH2 H Br mp = 203- ,,, N N N.'\NTN 205 OC ; T NEZ N O'. _ M+H-432 OH. 1l'S OH HN N () 1024 H Br NH2 H Br mp = 210- ,, N N ( ,, N N N nu Nz () OHI-Is"0 OH HN 1025 H Br NH2 H Br mp = 82-84 ,,, C ; 'il i' , M+H = 446 OHSsb OH HN N 1-UN () 1026 H Br NHs H Br mp = 86-90 ,. N N W N, HN Han N fun M+H = 462 N N O (+) ZON NN

EXAMPLES 1027-1038: By essentially the same conditions set forth in Example 341, Steps A and B only substituting the amines in Column 2 of Table 1002 and the compound prepared in Preparative Example 193.10, the compounds in Column 4 of Table 1002 were prepared.

TABLE 1002 Ex. Column 2 Column 4 CMPD 1027 Ho ho mp = 160- NH2 N N 1% 163 OC ; / N'N M+H = 434 HN If N ; 0_ 1028/)/X1 Br mp = 122- N H N N 124 °C ; N-'/M+H = 434 OH OH HN I + N, o- 1029 HO NH2 H Br mp = 153- Ho 156 OC ; M+H 408 HN -- 1030 HOu HO I Br mp= 170- ., \NyN 174 OC ; nu \ N, N M+H = 448 (Na 0- () 1031 HOu HO H Br mp = 166- H ber N H N, N M+H = 434 HN I + N, o- 1032 HO HO H Br mp = 167- N,, N,, 2 _N M+H = 434 HN \ N _ N, o- 1033 HO/NH2 HO H r MH+ = 393 N ruz HAN 1034 Br mp 157- 160 OC ; N M+H = 447 OH OH HN 0- I I 1035 NH2 N N (Br mp = 164- 168 oc ; M+H = 448 oh OH HN I + \ N, _ 1036 NH2 H Br mp = 165- N . I 0., N, OH N M+H 448 OH HN /ici N ; _ 1037 Br mp = 131- NH NRNN 135 OC ; N M+H = 447 OH OH HN Ruz N 1038 oH Ho Bu NZ Nez HO. HN /1 I I

EXAMPLES 1039-1041 : By essentially the same procedure set forth in Example 340 only substituting the amines in Column 2 of Table 1003, the compounds shown in Column 4 of Table 1003 were prepared.

TABLE 1003 Ex. Column 2 Column 4 CMPD 1039 Ho NH2 H Br mp = 210- HN N, if M+H = 392 HO kan I I N 1040 HOu HO I Br mp= 128- I ber . n H \ NN M+H = 432 () han kan N 1041 HOu HO Br mp = 148- 151 OC ; Han N HAN N

EXAMPLES 1042-1057: By essentially the same procedure set forth in Example 340 only using the appropriate 5-chloroderivative and substituting the amines in Column 2 of Table 1004, the compounds shown in Column 4 of Table 1004 were prepared.

TABLE 1004 Ex. Column 2 Column 4 CMPD 1042 HO HO H Br M+H= NH2 N N\ (500. 3 un HAN. HN I 1043 ber M+H= NH N,, Nl 514. 1 0 0 iNoN/2 OH OH HN HN 0 1044 HO/2 H Br M+H= Ho 460. 3 HN HN HN 0 1045 HO oNH2 H Br M+H= HO N N 477. 1 Nz HN HO IRE 0 1046 HO/2 H Br M+H= HO 505. 1 N HAN HN HN) rN 0 1 1047 HO~NH2 H Br M+H= HO-,, _, N N 505. 1 A j'NN han HN zu 1048 ber M+H=531. 1 NH N N\ ( WNH WN 44 OH OH HN HN 0 1049 HO~NH2 N N M+H= HO 477. 1 N HN HN\ ^Ni han 1050 HNH2 H Br M+H= 505. 1 C C XN_N HN HN 0 0, NH2 H Br M+H= HO N N 505. 1 , non HN Y" 0 1052 Br M+H= NN N N (531. 1 -Y N OH OH HN HN rN 0 1053 Br M+H= ON NH N 514. 1 C Y OH OH HN o o 1054 NH2 H Br'M+H= H Br. M+H= HOI-I 488. 3 1 8813 HO HN 0 1055 NH2 H B r _ l M+H= 4. 3 HA HAN HN HAN. Ho 0 1056 H NH2 H Br M+H= HO N N 488. 1 HAN HN HAN HN N N M+H= 488. 1 MH HO B r7 HN 488. 1

I I I # ASSAY: BACULOVIRUS CONSTRUCTIONS: Cyclins A and E were cloned into pFASTBAC (Invitrogen) by PCR, with the addition of a GIuTAG sequence (EYMPME) at the amino-terminal end to allow purification on anti-GluTAG affinity columns. The expressed proteins were approximately 46kDa (cyclin E) and 50kDa (cyclin A) in size. CDK2 was also cloned into pFASTBAC by PCR, with the addition of a haemaglutinin epitope tag at the carboxy-terminal end (YDVPDYAS). The expressed protein was approximately 34kDa in size.

ENZYME PRODUCTION : Recombinant baculoviruses expressing cyclins A, E and CDK2 were infected into SF9 cells at a multiplicity of infection (MOI) of 5, for 48 hrs. Cells were harvested by centrifugation at 1000 RPM for 10 minutes.

Cyclin-containing (E or A) pellets were combined with CDK2 containing cell pellets and lysed on ice for 30 minutes in five times the pellet volume of lysis buffer containing 50mM Tris pH 8.0, 0.5% NP40, 1 mM DTT and protease/phosphatase inhibitors (Roche Diagnostics GmbH, Mannheim, Germany). Mixtures were stirred for 30-60 minutes to promote cyclin-CDK2 complex formation. Mixed lysates were then spun down at 15000 RPM for 10 minutes and the supernatant retained. 5ml of anti-GluTAG beads (for one liter of SF9 cells) were then used to capture cyclin-CDK2 complexes. Bound beads were washed three times in lysis buffer. Proteins were competitively eluted with lysis buffer containing 100-200ug/mL of the GIuTAG peptide. Eluate was dialyzed overnight in 2 liters of kinase buffer containing 50mM Tris pH 8.0, 1 mM DTT, 10mM MgC12, 100uM sodium orthovanadate and 20% glycerol. Enzyme was stored in aliquots at-70°C.

IN VITRO KINASE ASSAY: CDK2 kinase assays (either cyclin A or E- dependent) were performed in low protein binding 96-well plates (Corning Inc, Corning, New York). Enzyme was diluted to a final concentration of 50). ig/mi in kinase buffer containing 50mM Tris pH 8.0, 1 OmM MgC12, 1 mM DTT, and 0. 1 mM

sodium orthovanadate. The substrate used in these reactions was a biotinylated peptide derived from Histone H1 (from Amersham, UK). The substrate was thawed on ice and diluted to 2 µM in kinase buffer. Compounds were diluted in 10% DMSO to desirable concentrations. For each kinase reaction, 20 gui of the 50 llg/ml enzyme solution (1 Ug of enzyme) and 20 p1 of the 1 ; j. M substrate solution were mixed, then combined with 10 ttI of diluted compound in each well for testing. The kinase reaction was started by addition of 50 p1 of 4 pM ATP and 1 ) n. Ci of 33P-ATP (from Amersham, UK). The reaction was allowed to run for 1 hour at room temperature. The reaction was stopped by adding 200 ul of stop buffer containing 0. 1% Triton X-100, 1mM ATP, 5mM EDTA, and 5 mg/ml streptavidine coated SPA beads (from Amersham, UK) for 15 minutes. The SPA beads were then captured onto a 96-well GF/B filter plate (Packard/Perkin Elmer Life Sciences) using a Filtermate universal harvester (Packard/Perkin Elmer Life Sciences. ). Non-specific signals were eliminated by washing the beads twice with 2M NaCI then twice with 2 M NaCI with 1 % phosphoric acid. The radioactive signal was then measured using a TopCount 96 well liquid scintillation counter (from Packard/Perkin Elmer Life Sciences).

IC50. DETERMINATION : Dose-response curves were plotted from inhibition data generated, each in duplicate, from 8 point serial dilutions of inhibitory compounds. Concentration of compound was plotted against % kinase activity, calculated by CPM of treated samples divided by CPM of untreated samples.

To generate IC5o values, the dose-response curves were then fitted to a standard sigmoidal curve and IC5o values were derived by nonlinear regression analysis. The thus-obtained IC50 values for the compounds of the invention are shown in Table 87. These kinase activities were generated by using cyclin A or cyclin E using the above-described assay.

Table 87 CMPD Example IC50 (M) ber 0. 020 0. 029 - ; <Xr f 3 0 032 HN N Ber 032- 0. 024 '/v HAN HAN. HN 4 0. 011 /N F N-N HN N ci 5 0. 021 zu 5 0. 021 N I N kN I I Br 0. 003 ION Cl HAN y ZON \ N 6 0. 064 0. 029 F \ N, N HAN HN N ber 7 0. 01 0. 006 C"l N HAN HAN N Br 10 0. 042 N\ ( --- HN N N Br 12 0. 17 Y NON HO N-N HAN CN 16 0. 62 N tN Ck HO zu HAN 1 5. 6 N HO kan ONYX non Ber 3 0. 14 ONYX NON HN HN N As demonstrated above by the assay values, the compounds of the present invention exhibit excellent CDK inhibitory properties.

While the present invention has been described with in conjunction with the specific embodiments set forth above, many alternatives, modifications and other variations thereof will be apparent to those of ordinary skill in the art. All such alternatives, modifications and variations are intended to fall within the spirit and scope of the present invention.

TABLE 43 Ex. Compound m/z Ex. Compound m/z zu 0 Br N 0 4301 BsNRn O \ 4301 N_NsfI 457. 25 4305 N N ? 487. 27 0 r 0 r N0 N N) Br O B N O \ 4302 V 471. 26 4306 V 487. 27 C'43 \ N S j Br 0 Br N20 VS Br O 4303 aS ° 477. 26 4307 NWNS 487. 27 Na N i tN AN -w--w- O/N Br p Br N O N 4304 N_Nt 483. 27 4308 N_Nf 494. 27 N N N Ex. Product m/z Ex. Product - _ s/, a i ex N O N O 4309 4313 509. 28 N 16ion 0 \ N O bar O F tg X 4310 500. 27 4314 NN r 512. 28 cl 0 1 0 \ N bozo Br N O N 503. 28 4315 N-N 513. 28 NN It, N 16ion No O Br \ N O 4312 N>NS 505. 28 4316 NSNX 513. 28 NN/ N N 6 6 Ex. Ex. Product m/z Ex. Product m/z 4317 y 4321 o Xi N O 518. 28 Y"523. 29 N-N N-N y /R \ N \ N 4318 4322 if er sr o 518. 28 N 523. 29 N_NorI N_Ns¢I N Nn N N H fo 0 519. 29 523. 29 N N 0 0 N N // N N \ N Br rn f 4320 4324 Bu r N 521. 29 N N J 525. 29 N o 6 // 1. Ex. 1. Ex. Product 2. m/z Product 2. m/z riz zu Br N a oS 1. 4325 1. 4330 2. 527. 29 2. 533. 29 N N N N 0 Br ci Br N/CI \ r N u \ N 1. 4326 4331 N 2. 527. 29 N X N) CN tN \ I..,, Br N 8 1. 4327 1. 4332 N_N 2. 532. 29 vu 2. 533. 29 N N 16N 16IN \ N \ N foc r N 0 Br 1. 4328 B, N N 1. 4333 N_N N 2. 532. 29 N_Nf 2. 533. 29 ton N 2. 533. 29 N 16ion 0 \ N \ N B SNRX 1. 4329 Nyo 1. 4334 1. 4334 2. 532. 29 N_Nf 2. 537. 3 N N I \ N \ N 1 Ex 1 Py Product, Product'-- 2. m/z 2. m/z HaC O _. G Br N 0 1. 4335 1. 4340 AN AN N N // \ N \ N O i \ J i Br N''p g O 1. 43362. N 0 1. 4341 N N ? 537. 3 N-N N M. N-nu zizi bzw hic f'tu Br N-. 0 V 2. 539. 3 0 (j 2. 546. 3 N zon / NN N \ N N 16ion 1. 4343 N 2. 539. 3 N N ? 2. 547. 3 k 0 0 N0 1'. 4339 0"° 1. 4344 NN/2. 539. 3 N. 2. 547. 3 N. nu 6 6 16N 16IN Product 2 : m Product 2, mlz s of 1. 4345 1. 4350 SNRX 1. 4345 WNR 1. 4350 /2. 549. 3 N. N 2. 553. 3 N N Nx Br m Cbz CI / N Br N \ sr N ° 1. 4346 1. 4351 2. 550. 3 N-N N N 16ion t/o Br X r er 1. 4347 B ° 1. 4352 N-N ;-) 2. 557. 31 1'1 6 6 AN N N \ N \ N N 0 O i I \// Ny ON 1. 4348 1. 4353 2. 551. 3 N N // \ N \ N F Ber/ Nez Br ° 1. 4349 N N'1. 4354 N 2. 551. 3 N 2. 561. 31 N N \ N 1 Ex 2 1 Ex Product'''Product'' I o \ N 1 1. 4355 0 1. 4360 2. 561. 31 2. 569. 31 NEZ N - 0 CH3 Br N N N 1. 4356N 1. 4361 2. 561. 31 N 2. 574. 32 N \ N ßN 4357 CI Br Br N O 1. 4362 N_Nvl 2. 561. 31 2. 573. 32 N // \ N 0 NCH v \I v N 1. 4358 NN i 1. 4363 N 2. 561. 31 N 2. 573. 32 ion N Br Br NJW d 1. 4359 B oS0 1. 4364 2. 569. 31 N 2. 575. 32 N / -, 1. Ex. ., 1. Ex. Product 2. m/z Product 2. m/z G \ I \ 1 Ci gaz Sr N X0, c ? N / 2 NN/v 2. "\ - - 575. 32 Na 585. 32 N zu I G a Br N O 1. 43666 1. 4371 2. N-N 2. N) 575. 32 NNtl 583. 32 N N-583-32 _, C1 NO O 1. 4367 1. 4372 2. 2. N 574. 32 N 585. 32 N N // \ I Ns 1 s I"e Br 1. 43688 1. 4373 Nz 2. 583. 32 Nx 585. 32 N 0 N O i Br 1. 4369 1. 4374 2. 583. 32 N 597. 33 6 Product 1. Ex. 2. m/z 1. 4375 B. rr" '' 1. 4375 2. 499. 27 Br N 0 Br N O 1. 4376 2. 493. 27 N CF a AcocA C \ I C 1. 4377 N N ? 2. 535. 29 N ~ \ N TABLE 44 Product 1. Ex. 2. 1. Ex. 2. m/z Product m/z Br Br N N /NN/N--N Br Br N \= (1. 4401 N 1. 4406 0 N 2. 471. 3 ° N 2. 487. 27 0 N N Br Br N/ N N N 1. 4402 1. 4407 2. 475. 26 2. 487. 27 s o s\CH, bN N Br Br Ber /--\ -- N 1. 4403 N 1. 4408 o N 2. 483. 27 2. 487. 27 po N CH, \N hic Br Br N N-N N N N 1. 4404 N 1. 4409 o N 2. 481. 26 XN < 2. 494. 3 - N Bu ber Br Br Br Br N N N N N-N 1. 4405 N 1. 4410 orb N 2. 485. 27 0d N 2. 496. 27 _ N Product Ex Product 1-Ex. _ m/z 2. m/z Br Br bu ber C, N N N--N N N-N 1. 4411 N N-N 1. 4416 N 2. 499. 27 0 N 2. 507. 28 s i- /N \// Bu ber N C /. N "v"AN1 (} 4AN1 N 2. 4412 N 1. 4417 0=XX N 2. 499. 27 °) (N 2 509. 3 S \N 0 \N Br Br er _ Br < N-N N-N --n --" /N 1. 4413 N 1. 4418 0 2. 500. 27 3 X tN 2. 512. 28 HIC Br Br /N N I I -N N- 0=S N 1. 4414 N 1. 4419 2. 503. 28 X N 2. 513. 28 0 \N ci3 N Br Br -N N /N I non N 1. 4415 N 1. 4420 2. 505. 28 N 2. 513. 28 \N S/ \N Product 2. m/z Product 2. m/z 2. m/z N-N- /\, N N 1. 4426 o N 2' N 2. 521. 29 513. 28 Br Br N /NN NN 1. 4422 1. 4428 o N 2. o 0 N 513. 28 2. 521. 29 513, 28 X X S 513. 28 O tN Br Br N N-N _N 1. 44. 23 N N 1. 4428 2. o 518. 28 2. 523. 29 518. 28 Bzw Nez Bu or //N N /NN 1. 4424 N 1. 4424 N N-N 1. 4429 2. 523. 29 Br Br 518. 28 N N N Br Br '__N-. N/NN 1. 4425 N 1. 4430 2. 519. 3 ° N 2. 523. 29 \ o-cr- Product., Product, 2. m/z 2. m/z Br Br ,-N/NN J 1. 4431 N 1. 4436 2. 523. 29 N 2. 527. 29 b 0 N bu ber c 1-~ N/---t __ (W -V-M \ 1. 4432 1. 4437 2. 525. 29 0 N /N 1 /ils Br B r _ _ B. _. _. N IJ 'r__l (N/N.-N 1. 4433 N 1. 4438 2. 525. 3 0S N 2. 532. 29 - 1 XN N XN s _-11 Br Br N I I N/I NN N-N 1. 4434 N N N-N 1. 4439 0 ci N 2. 527. 29 AN 2. 532. 29 N N Br Br Bu bu N-N _J (N_N --, N-N N 1. 4435 N_J v__ O N 1. 4440 R N 2. 527. 291 X o zon ci 1 Ex 1 Ex ---, Br Br N N I (--//N Br 1 _ Br N 1. 4441 <N 1. 4446 I w m Ch o Bu ber bu ber N N /NON O w 1. 4442 o N 1. 4447 2. 531. 29 2. 537. 3 o N6/ Br Br ___. ___.. _ _. rJ-N/N N 1. 444. 3 1. 4. 448 2. 533. 29 2. 539. 3 --- N s N .. _.-__..-____-. _. __.. ___ _ __ _____ ______ Ber N- ?/ N /NJ N NEZ 0 N N 1. 4444 N-N-N 1. 4449 CH, 2. 535. 29 0 S-CF N 2. 539. 3 cl Br Br Br Br N N. N N . 1. 4445 o N 1. 44. 50 O N 2. 537. 3 2. 539. 3 \N \N 0, _, O Foc / H3C 1. Ex. 1 Ex 1 Pv Product 2. m/z 2. m/z bu ber Br Br N- N 1. 4451 o N 1. 4456 2. 541. 3 N 2. 54. 9. 3 s Br Br __ Bu N , N /NN Cr -c/d-N N- _ N N 1. 4451 H, C 0 N 1. 4457 2. 543. 3"c zon 2. 550. 3 0 N N i o N o 1. 44. 53 2. 546. 3 ° N 58 2. 550. 3 N N- Br Br N /N_. [ Cr--- N_N N 1. 4454 o N 1. 44. 59 : 2. 54. 7. 3 2. 551. 3 =+N 9/N_N 0 0 Br Br , N-'N-_ --- NN 1. 4455 N 1. 4460 0 N 2. 547. 3 2. 551. 3 cob/0 . 1 P tM 1 Fx 1 Fv 2. m/z 2. m/z Br N N-N N N-N 1. 4461 N N N 1. 4466 0=t N 2. 549. 3 F= (2. 561. 31 O F F ber B N N-N !/NN/N. _N Nez b N 1. 4467 \//° 2. 553. 3 F o N 2. 561. 31 N F F F/\ ---------------- Br Br -N-N N N N 1. 4463 N 1. 4468 2. 557. 3 ° N 2. 561. 31 Ob 0- w"'U 0 bu ber au - /NN N-\" N-N 0 N 1. 4464 N 1. 4469 2. 557. 31 ° N 2. 561. 31 8 tN bN N Br Br Br Br //N N /NN N o= (7 N 1. 4465 N 1. 4470 a, d 2. 558. 31 o N 2. 562. 3 / N Cil EX* Product 1. Ex. Product 1. Ex. prou Br.. _. _-_Br N N-N-N 1. 4471 - 1. 4476 N 2. 569. 31 0 N 2. 572. 31 0 N N /\/N-/\ N Bu Br N/ N N N 0 N 0 O= (, N 1. 4472 o N 1. 4477 2. 569. 31 Q tN 2. 573. 32 Non Br Br N f I (% N-N--/6/L 0 N N-N 1. 4473 N-N 1. 4478 N 2. 572. 31 2. 574. 32 ci N Cil Cl N/I N I I /_-_/=, N-N N-N N-N , c N 1. 4474 O=p oR N 1. 4479 2 572. 31 o tN 2. 576. 32 '''"'' N, N i i Br Br --- BUm --l (N N _ u/NN 1. 4475 1. 4480 1. 4480 N 2. 575. 32 IN 2. 583. 32 N 1 Fx 1 Pv Product-, Product,- e /N N N Br Br N ( 0t aN 1. 4481 o d N 1. 4486 o, N 86 2. 583. 32 a-s- 0 2. 585. 32 O Br Br //N N/I s 4AN SX /=\ 1. 4482 N N-N 1. 4487 0 N 2. 583. 32 0 N 2. 597-33 d tN 0 N N N Br Br N 1. 4483 N 1. 4488 N 0 N 2. 499. 27 C con v r N r r Br NEZ N-N 1. 4484 2. 585. 32 0 Nez Bu Ber N N-N N 1. 4485 2. 585. 3 CN --4-C Jj TABLE 45 Product Product Product 2. mlz 2. m/z 2. m/z . _. _.. /v/\ ___ er N-a e r a B N-u N N N zon L> 0 H, C-'C3 N 0 C, 0 Its-N \ ^N \ iN I \ N I 1. 4502 N N \ 1. 4507 \N, N \ 1. 4512 2. 526. 29 2. 542. 3 2. 554. 3 Br ci N- N /S i/ cl er 6r a 9r N-CI 1. 4503 1. 4508 N 1. 4513 2. 532. 29 2. 542. 3 2. 554. 3 0=1 0 S, N-0 a roc Vs ........ ........ Br/N_ Q 6r a 9r N_ Q I 1. 4504 r v 1. 4509 i 1. 4514. 2. 538. 3 2. 542. 3 2. 555. 31 N 0 0 0= O cl HO / 'cl Nz N N 1. 4505 N N \ 1. 4510 i 1. 4515 0 o : po ckc"l b b r Product 1 Product 1. Ex. Product 1. Ex. 2. m/z 2. mlz 2. m/z rv i rv cl a C3 ^ N I eN/N N N 1. 4516 N N-p 1. 4521 1. 4526 2. 560. 31 2. 568. 31 o 2. 574. 32 ou N Q CIP Q X O "CW-N N-GY N_ C1 B N-f7 & N N N N N N 1. 4517 1. 4522 1. 4527 2. 562. 31 2. 568. 31 2. 576. 32 N 0 O N Br Y / N N N. N N N i v 1. 4518 N 1. 4523 N 1. 4528 2. 564. 31 2. 568. 31 C 2. 576. 32 N O O C l b o-b b 0 b N-C'ci N- ? C B\/\ \. -/ \ \-/\ N N N N. N N N 4519 N 1. 4524 N N 1. 4529 2. 567. 31 2. 573. 32 2. 578. 32 N 0 CH 0-CF a Sr ci "° N I-" I /\ er a e'a er Pl-G1 N 1. 4520 1. 4525 | N | 1. 4530 2. 568. 31 2. 573. 32 2. 578. 32 N O N CFt . 1 E.. _. 1 Ex _ p duct | 1 É roduct 1. Ex. Product 1. Ex. Product 1. Ex. 2. m/z 2. m/z 2. m/z X WN) 4, Nt N a N_ a a N-a er - % rN \Ho-ai 9 j U u-e X Q Q Br <> a N<NQ Br@ra 1. 4531 N 1. 4537 A 1. 4541 2. 578. 32 2. 582. 32 2. 588. 32 N O O p- a \ eo G & N-CI Br/ /\,,'N X 1. 4533 + 1. 4538 W 1. 4543 1 2. 578. 32 2. 582. 32 l ß | 2. 588. 32 N N O O O _. ... -. -- Br N_ a Br ! L a I N Br N N N N | O l i Q l Q IB'N4Xa f I Aa I I B, << a | % NgN l I DrtH l l WNt l l 1. 4533 1. 4538 N 1. 4543 2. 580. 32 2. 587. 32 2. 588. 32 ou O t 0 cl ci "N'N N N l \/ ! \ " e ey l B' J N N r 1. 4534 1. 4539 1. 4544 2. 580. 32 2. 587. 32 2. 588. 32 N N 13 ,, don Br N'a e er ° N N/N 1. 4535 1. 4540 1. 4545 I w I I U I 11 A 2. 582. 32 2. 587. 32 2. 590. 32 N N O O o a- 1 Fx 1 Ex 1 Pv Product 1. Ex. Product 1. Ex. Product 1. Ex. 2. m/z 2. m/z 2. m/z rv rv rv a B, , ri a er Ji a N N, N- Y N 1. 4551 1. 4546 1. 4551 1. 4556 2. 588. 32 2. 593. 33 N 592. 33 N N ltcI 5 -sv N /N-G1 er H Br/'N N f"A 1 4552 \- 1. 4547 1. 4552 1. 4557 i 2. 588. 32 2. 596. 33 592. 33 0 N 0 b 0 a cl F a E-a \Cl J'-N-a a I r v 1. 4553 N/N 1. 4548 ? 4553 1. 4558 2. 588. 32 2. 2. 596. 33 N V'o O Q I 11 X} Bn a 80 a 8, N- CI \ 1. -h5Jf N N p 594. 33 1. 4559 2. 588. 32 2. 598. 33 N 594. 33 N Br a N-G Br N-a s r 1. 4550""1. 4555"N 1. 4560 i 12. 590. 32 p 2. 2. 601. 33 0 0 o s-, i i v v 1 Fx 1 Ex 1 Pv Product., Product-, Product'-- 2. m/z 2. m/z 2. m/z r r r D7-C s, /rv-a N-a Br r Ar ci B N \ <N N N N I N N N N 1. 4561 1. 4665 1. 4571 2. 602. 33 2. 605. 33 2. 612. 34 N o ouzo / O O a N-p Br N-O air\/ N N N N N N 1. 4562 1. 4567 1. 4572 C 12. 602. 33 iN 2. 606. 33 0g 2. 612. 34 0 N v i ovo v i X Za Q tN/NU N {B'tN'NQ a N ry N N N 1. 4563 1. 4568 1. 4573 2. 604. 33 2. 606. 33 2. 613. 34 N 0 0 zu - '1 - N N_ CI Br N N N 1. 4564 1. 4569 N 1. 4574 2. 603. 3 2. 606. 33 2. 616. 34 a . s X Q Q F er C ° ber Br _ N N N Np 1. 4565 zu 1. 4570 1. 4575 2. 605. 33 2. 608. 33 2. 616. 34 N 0 F _ F /1 0 1. Ex. 2. 1. Ex. 2. 1. x. 2. Product 1. Ex 2. Product 1. Ex 2. Product 1. Ex 2. O Q O N N O a B, tNU a m/z m/z m/z N-ci N ers / N N N N N N 1. 4576 ! 1. 4581 X 1. 4586 2. 616. 34 2. 624. 34 2. 630. 35 toto 0=/c=/ ° i r io Or B, rr a a N-a er X B, Br sYN, NU a N N N N 1. 4577 1. 4582 1, 4587 V 2. 616. 34 v 2. 629. 35 2. 630. 35 0 0 0 I- N ci a /\ a en H-o Q Br N-a Ar N I \ N N 1. 4578 583 1. 4588 i 2. 616. 34 < 2. 629. 35 2. 630. 35 o o o a N N Q Q X a ar N-a N G erN-a N 1. 4579 N 1. 4584'p 1. 4589 2. 616. 34 f 2. 630. 35 2. 631. 35 0 0 ou 0 0 C i ° o I p I r 1. 4580 Qa X-t IN ! r ! N N N N N N /\N 1. 4585 > 1. 4590 2. 624. 34 2. 630. 35 r 2. 638. 35 i 0 0 0 i i i i Product m/z Product m/z r cri bar YO er ? N _ 1. 4591 1. 4596 2. 638. 35 2. 652. 36 \/ U ; p \0/ L N N-1. 4592 NIN N-p 1. 4597 2. 640. 35 o 9 2. 486. 27 ° \/ N- ? l /\/\ Br\ N-Q N N 'N I 1. 4593 N N 1, 4598 2. 640. 35 2. 554. 3 N 0-\/ O O 0 Br bu cri N y 1. 4594 N Na 1. 4599 2. 640. 35 out 2. 548. 3 zizi a v i i i a ., N -N 4, N N N N 1. 4595 i 1. 45100 2. 640. 35 2. 8 a 0. 5 Cl6 i TABLE 46 Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z N ion 'ion N/N 1. 4601 N N 1. 4606 2. 512. 28 2. 540. 3 ' N-C, ci N N N 1. 4602 N N 1. 4607 I 9 2. 526. 29 2. 542. 3 l oWb \=tN 1 0 i , _.. __. - _ _ er 1 ( N 1. 4603 N N 1. 4608 I XN 2. 532. 29 Q 2. 542. 3 /\ N N a ci /\/\ N-G er N-G Br 1. 4604 "N N 1. 4609 2. 538. 3 2. 542. 3 N 0 , lut4 o Br N-CI B N-G 1. 4605 1. 4610 . 2. 536. 3 N N 2. 547. 3 WC--o O 1 Ex 2 1 Fx 9 Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z ---------- Art eN N N'N 1. 4611 1. 4616 2. 551. 3 2. 560. 31 Ck 0 \- C Br N CA N_ CI er N-CI Br 1. 4612 1. 4617 2. 552. 3 2. 562. 31 N N 0 0 N-G BrN-G Br 1 1. 4613 N'1. 4618 N-ZN 2. 552. 3 2. 562. 3 N ; N-CI Br N-G Bu w N 1. 4614"N 1. 4619 2. 555. 31 2. 567. 31 N O Fiat N-CI g N-G Br // N w N 'N N 1. 4620 t 2. 558. 31 2. 568. 31 \ \-. O-CH3 i Product m/z 2 Product m/z m/z CA N-ci N N 1. 4621 N N 1. 4626 2. 568. 31 > 2. 574. 32 o 1 \ s /\/\ Br N-C B N-G W oN Na 1. 4622 1. 4627 t 2. 568. 31 ! 2. 576. 32 H" IN N \ l U N-G Br N-G Br/1'\N , N 1. 4623 N 1. 4628 2. 568. 31 t 2. 576. 32 0 o Br N-C3 Sr N-a IN BrgNf Ci I Dr &tN Nf a N, 1. 4624 1. 4629 2. 573. 32 2. 578. 32 zozo N N Br N-bl 8 N-G N/N/ N N 1. 4625 N 1. 4630 2. 573. 32 2. 578. 32 o-cr 0 0 0 n . 1. Ex. 2. .. 1. Ex. 2. Product, Product, m/x m/z Br N-a Br,, N- Br >tN Nf a BrtNf a N N 1. 4631 NoN N 1. 4636 2. 578. 32 N a 2. 582. 32 CA , CH. N 0, O O a Br,,, N- N N N 1. 4632 N'N 1. 4637 2. 578. 32)' -582. 32 N a 0 W\ \=tN Br N-G B PL G N I N 1. 4633 N N 1. 4638 Q N 2. 580. 32 2. 587. 32 N N N O O / ----- IN Bu N N 1. 4634 N 1. 4639 2. 580. 32 N 2. 585. 3 N N B N-CI Br Nz 1. 4635'N N 1. 4640 2. 582. 32 2. 585. 3 N 0 Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z a ex 1. 4641 N N 1. 4646 2. 588. 32 2. 592. 33 0 O N Br N-G Br N 1. 4642 N N 1. 4647 2. 588. 32 2. 592. 33 . b Nt N-a Sur N N Br er Y1 NJ N N N N 1. 4643 2. 588. 32 2. 592. 33 )'-\ CA ar r'dN \ U Br N-G Br . 4644 N N. 2,. 2. 588-32 588. 32 2. '-\cn, \ °0 0 er N cl C4 N'Nn 1. 4645 iN'N N 1. 4650 t 2. 590. 32 2. 594. 33 s 0 O 1 Fx ? 1 f=Y 7 Product 1. Ex 2. Product 1. Ex. 2. m/z tN f BrtNSCI M : : x Nn 1. 4651, N 1. 4656 2. 594. 33 V 2. 602. 33 i S 0 cl3 0 er N 1. 4652 4, N N 1. 4657 2. 596. 33 vow 2. 602. 33 /\ 0 / .. Br, N- G B G. Ion N N 1. 4653 NN 1. 4658 2. 596. 3 2. 604. 33 /\ /\ 04 Nm Br N N \ 1. 4654 \-1. 4659 2. 598. 33/ 0 2. 603. 3 Nv 0A N O sr N-ci Br N-C4 N N 1. 4655 N 1. 4660 H, C 2. 601. 33 0 2. 605. 33 ,, o 0 \/O'/ Product 1. Ex. 2. Product 1. Ex. 2. m/z i v r v - (N oN I CN I NN 1. 4661 1. 4666 2. 605. 33 2. 612. 34 0 -= -- 0 /\/\ \-N"\- NN I N I > 1. 4662 No 1. 4667 2. 606. 33 2. 612. 34 b N N X s X Br N-CI Br\, N- CI N 1. 4663 NN 1. 4668 0 2. 606. 33 V 2. 613. 34 0X N 0 0 N IN CA ci Et bar 1. 4664 Brif 1. 4669 2. 606. 33 W 2. 616. 34 oR 9 O O F _ a Br N-G /arr/ N Ne 1. 4665"dz 1. 4670 A, 2. 608. 33 2. 616. 34 0 a F F F 1 Ex 2 1 Ex ? Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z er N-a er jr4 \/ -N'Nn 1. 4671 N Na 1. 4676 2. 616. 34 t 2. 624. 34 n \ o \/ 0 '} p B er N-ci Br N N/ N 1. 4672 NN 1. 4677 2. 616. 34 t O 2. 629. 35 N 13r a oc ILC B G Br N-G N N N 1. 4673 N 1. 4678 2. 616. 34 2. 629. 35 N N Br, ci a ir t4 N /\ Br N--. CI N N 1. 4674 N 1. 4679 -z 2. 616. 34 X n 2. 630. 35 G Ny' ° °C 0 /\-/\ N-G BrN- bu / N 1. 4675 1. 4680 2. 624. 34 2. 630. 35 N O O Product 1. Ex. 2. Product 1. Ex. 2. /\ m/z m/z \NN I \ 'Na 1. 4681 N 1. 4686 2. 630. 35 2. 638. 35 2. 638. 35 N/\ 0 er/N-a N-ci Br N N 1. 1. 4682 N 1. 4687 2. 630. 35 \ 2. 640. 35 0 N cl N-G1 B N-CI Br N N 1. 4683 N, 1. 4688 2. 630. 35 tNH < 2. 640. 35 N 0 0 a N/N N Br N-CI bu ci Un 1. 4684 \ N 4689 2. 2. 631. 35 o i a a a/eyr/ N N W 1. 4685 W 1. 4690 2. 638. 35 2. 640. 35 N Neo O O i O i Product 1. Ex. 2. m/z N Br N 1. 4691 2. 652. 36 / 0 O N-a IN N 1. 4692 2. 484. 3 N-cri O rN-f N N 1. 4693 2. 554. 3 _- % \ l N N 1. 4694 Br N-CI 1. 4694 N 2. 548. 3 N N-ci N 1. 4695 V H3C 2. 590. 32 FC - Cbz foc H, c TABLE 47 1 Py ? 1 Ex 2 1 Pv9 Product 1. Ex. 2. Product 1. Ex. 2. Product 1. Ex. 2. Br Na w 1 Bu N 1. 4701 N 1. 4706 1. 4711 2. 498. 27 2. 528. 29 2. 544. 3 0 N 0 NEZ N N N o cit ° i \ < ? ° ? a/ a ; er N\ w e v bu NN N N 1. 4702'L 1. 4707 1. 4712 2. 512. 28 0 2. 528. 29 2. 546. 3 N'. O O 0 N 0 N itc Cl a cl N_- Br v 1 Br 1 Br , N N non Y 'Y f N 1. 4703 N 1. 4708 N 1. 4713 2. 518. 28 2. 535. 29 12. 548. 3 N N 0 N B, Cl N B N Nv v v N N 'N'N N N 1. 4704 N 1. 4709 1. 4714 2. 524. 29 ruz 2. 540. 3 2. 550. 3 o ci-ni ouzo v N O & N NN/ N tJ, J.. " 1. 4705 N 1. 4710 N 1. 4715 2. 528. 29 qu 2. 541. 3 2. 553. 3 o' ( N N Cbz on Product I. Ex. 2. Product 1. Ex. 2. Product Ex. 2. m/z m/z m/z Cl Br Br N\ Br Br IJ Nv N/S f N N N 1. 4716 N 1. 4721 N 1. 4726 2. 554. 3 2. 562. 31 2. 568. 31 N O N N t N$4 N4 H, c A \NN Bf _, v Br v N N 1. 4717 1. 4722 N 1. 4727 2. 554. 3 2. 562. 31 2. 568. 31 \ N O v N O N O So 6 CL. . __ N r4 N , Br Br N\ Br O 1. 4718 1. 4723. 1. 4728 9 O 2. 554. 3 2564. 31 2. 568. 31 N 0 N 0 N O NCO sur , r * 4 N N N N N 1. 4719 1. 4724 1. 4729 2. 559. 31 9 o. 564. 31 9 2. 573. 32 0 N N \ N \ I I N e 7- ey N N/_ A s A 1. 4720 1, 4725 1. 4730 2. 559. 31 2. 566. 31 2. 574. 32 N' 9 h M N N o i 1 Ex 2 1 Ex 2 1 Fx9 Product 1. Ex. 2. Product 1. Ex. 2. Product Ex. 2. m/z m/z m/z 1 I Br \ B v Ar Nv N 1. 4731 1. 4736 1. 4741 2. 574. 32 2. 580. 32 2. 588. 32 0 0 N coS/ n, c ! . _ _ _ _ ri _ _ N N N /NN/ N N 1. 4732 1. 4737 1. 4742 2. 576. 32 2. 582. 32 0 2. 590. 32 p N O N 1 e S 1/ N, N N, N a/' cy... i 1........ 6r N v Br N er N N 1. 4733 1. 4738 1. 4743 H, C2+ & S ; 2. 578. 32 2. 584. 32 2. 591. 33 N O N O N O N nu B bu ' sr N\ v ar v Br w' N N N 1. 4734 1. 4739 N 1. 4744 2. 578. 32 iN21 585. 32 2. 592. 33 o \ I 2. 592. 33 N 0 \ I cr, N O\ N 1 O/ a/1 a/\ a/1 Bu Ber Br NN/ N 1. 4735 1. 4740 1. 4745 2. 580. 32 2. 588. 32 _ 2. 592. 33 0 zu O I/Ov o aa, 1. Ex. 2. 1. Ex. 2. Product Product 1. Ex. 2. Product m/z a er/ I a/\ er BrX3 v Ex NN/\/ N'N N'N 1. 4746 1. 4751 1. 4756 2. 592. 33 2. 602. 33 X 2. 624. 34 NO N O N O / IN, non N a J \ a ar N\ I se N 1. 4747 N 1. 4752 1. 4757 2. 598. 33 2. 615. 34 2. 624. 34 N X NX3 Na N H3 H,/ / ON /__-I " /Br N B'N ar ) N IJ N'N/\ N N/ N 1. 4748 1 1. 4753 A 1. 4758 9 2. 598. 33 N o 2. 615. zinc 2. 626. 34 N O N 1 CN- J/\ \1 _ __-_. _.. _ a/\ a/\ e er r N N N N 1. 4749 1. 4754 1. 4759 2. 602. 33 2. 616. 34 \ B a ° F a 2. a/\ ci/\ er, t er Br N <N N J N f \ nN 1, 4750 N N 1. 4755 N N 1. 4760 2. 602. 33 XN-tO 2. 616. 34 o \ 6 F 6 a/\ 2. a 34 0 Product 1. Ex 2. m/z ber N N N N 1. 4761 2. 638. 35 N O °')' o Br N N 9. 4762 2. 472. 26 CH, Sur CH3 Y Ar \ w NN/ N 1. 4763 2. 534. 29 N O I/ TABLE 48 1 Ex 2 1 Ex 2 Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z Ber N- Cul 1. 4801 1. 48062. 2. 498. 27 N 528. 29 60 60 N r ber ci Cul CI \ NN N ; N 1. 4802 N 1 4807 2. 512. 28 2. 528. 29 0 o N "r Br N Br I sr i i i i a r Cl 1. 4803 N 1. 4808 2. 524. 29 2. 528. 29 i I o i I oI P_ ; N PN"r C4 oh t N N r % i % i G N"CI N N 1. 4804 N 1. 4809 2. 524. 29 2. 2. 540. 3 6N 0 6N 0 /N r/<N$r /I r/I r \ j \ j CI G N\ N N 1. 4805 N 1. 4810 2. 526. 29 2. 540. 3 N tN) N o 'Y''S V Product 1. Ex. 2. product 1. Ex. 2. m/z m/z /i/G N'i r [ N_r N N N 1. 4811 N 1. 4816 2. 544. 3 2. 562. 31 ] y ° I I N CH N 1 i IN bu //\/ a w N, N CI \/NN Cl 1. 4812 N 1. 4817 2. 548. 3 2. 562. 31 0 N 0. 'N/ N W _ Br I Br N a N Cl N 1. 4813 N 1. 4818 f. 2. 553. 3 J 2. 564. 31 H, tN XCH3 foc zer N r Cul cul Br CI \ NN CI \ NN ci N-N 1. 4814 N 1. 4819 N 2. 554. 3 2. 564. 31 i o w I N i oc r r _ P_ _ v CI CA N N NON 1. 4815 1. 4820 2. 560. 31 2. 568. 31 6N 0 6N 0 a I I 1 Ex 2 1 Ex 2 Product',''Product','' mlz size XN t $ _ N-N 04 N 1. 4. 4826 2. 568-31 2. 574. 32 6N 0 ci 0 6N r N r 9 Ber ex ci w N N a N 1. 4822 N 1. 4828 2. 573. 32 2. 576. 32 i o. 6N N N0 _-< __ ar ex i CI NN N 1. 4821 N 1. 4829 2. 574. 32 2. 578. 32 1 0 6N 00, N __ Bu \ i \ I i-N i N-N N-N N 1. 4824 N 1. 4829 2. 574. 32 2. 580. 32 o r I o m _. S ____ 'r W 'N r G NN G N N N 1. 4825 N 1. 4830 I 2. 574. 32 2. 584. 32 i o rl o 1 Fx* ? 1 fv Product'',"'Product.'= r ( zon N N 1. 4836 2. 588. 32 2. 2. 588. 32 616. 34 i I o w 1 o w I N I i _ _ wN r/N r _nô N N 1. 4832 1. 4837 2. 602. 33 2. Nz u Nu F/ F r Bf i i "N 1. 4838 1. 433 2. 602. 33 2. 626. 34 N PyN N/1 F G W N. N G NN 1. 4839 "1. 434. N 2. 2. 602. 33 o 626. 34 zizi w I o I i ce / r/ r i i i a N..'i a "1. 4840 1. 4835 2. 610. 34 564. 31 I I \ N \ I \ NO I/ t Nß 2. 610. 34 J No < 0 1. Ex. 2. 1. Ex. 2. Product m/z Product m/z m/z m/z NU N-Cl Tr'Y Tr 1. 4841 1. 4846 N 1. 4841 N 1. 4846 2. 535. 29 2. 568. 31 i I o i (o \ N \ I \ N \ I CI /I r/ Br f I j G \ NN G N. N 1. 1. 4842 N 1. 4847 2. 541. 3 2. 578. 32 i I o i I o N Nazi ouzo Br Br pin Gf w on w N N 1. 4843 N 1. 4848 2. 559. 31 2. 580. 32 tN) I o CH3 N i \ N 1 \ % G \ rv-'G ffN N 1. 4844 1. 4849 six 2. 559. 31 CN 2. 580. 32 N C, Cl N-N N / r/ r % i i i a w N, °'a N N 1. 4845 N 1. 4850 2. 564. 31 2. 584. 32 o i N /CFi // O Product 1. Ex. 2. Product 1. Ex. 2. M/z m/z OL/"' G NN CI \ NN N 1. 4851 1. 4856 2. 590. 32 &N 2. 616. 34 into W. N o I w S Cl a w a N-N 1. 4852 N 1. 485T 2. 591. 33 2. 624. 34 i o i I o I w k''en, - ;-----.----.-----.-- C6 in CA Cl N NI N 1. 4853 1. 4858 2. 610. 34 Nz 2. 626. 34 N w N W W c I I i r r i i i i G \ IJN CI N. N N 1. 4854 N 1. 4859 2. 615. 34 2. 537. 3 i I I o 6N N N N FiC FiC nu ber Bu ci _' N =9 Ntr G \ Nz N 1. 4855 1. 4860 N z 2. 615. 34 2. 550. 3 N I N'I. O ! 1 t=v 0 1 P : v ? Product I. Ex. 2. Product I. Ex. 2. m/z m/z if c w a N N a Y- a Nf 1. 4861 1. 4866 2. 554. 3 2. 587. 32 i o i o ) 10 Ber B, /et'/I r i i '% Cl _ CI 4862 1. 4867 1. 4862 N 1. 4867 6N 0. 2. 566. 31 N 2. 588. 32 Br Br y 5 N y/ N O Br Br "NX ci yin cl N-N 1. 4863 a N 1. 4868 2. 566. 31 l KN 0 2. 592. 33 o Br-"r 'Cl N N-Cl-6/ ci N N-N CI NN a N N 1. 4864 N 1. 4869 2. 578. 32 2. 592. 33 i o', o N N r \ i N w i _ i i / 1. 4865 1. 4870 N 2. 582. 32 2* 573, 32 zon off N N CI Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z Br i i i i a N-N Cl N-N/r N 1. 4871 N 1. 4876 2. 616. 34 2. 594. 33 a xi bu r Br "pin G \ NN CI NN WG 1. 4872 Y 1. 4877 2. 616. 34 2. 598. 33 ci _N I CI I N Br i i i i Br Br S-r"i SrT"i wN r X N$r 1. 4873 N 1. 4878 2. 624. 34 2. 592. 33 o i I oII wN N r [W N r r i N r I Br G NN 1. 4874 N 1. 4879 1 2. 638. 35 2. 569. 31 N I//I O O vu o_ a N-N/' /Br/ r _ G 'NN 1. 4875 1. 4880 0 2. 546. 3 C 0 2. 583. 32 o I N N OiCf'a N CFa O TABLE 49 1 Ex 2 f1 Ex 2 1 Pv9 Product 1. Ex. 2. Product 1. Ex. 2. Product 1 Ex. 2. m/z m/z m/z CA a Br Br v 4 N-N non NiN N N N N 1. 4901 N 1. 4906"1. 4911 2. 490. 27 2. 518. 28 t 2. 529. 29 N N 0 foc cri Br u N.-N N-N N-N F _ _ _ _ _ 2'N W W w/ w y \ N N N N/N N/ 1. 4902 N 1. 4907 N 1. 4912 2. 504. 28 2. 520. 29 2. 532. 29 JNJ O cils Ber Bu Ber N B\ \ \ /N N/NN/ N 1. 4903 No 1. 4908 N 1. 4913 c 2. 510. 28 2. 520. 29 2. 532. 29 N N N S U l_% o 0-1-CO bu ut N/ N N N 1. 4904 1. 4909 N 1. 4914 2. 516. 28 6N 2. 520. 29 6N 2. 533. 29 N o N °o \"c=cr° Br O N O ci/ a/\ Bu N N N N 1. 4905 N 1. 4910 1. 4915 2. 516. 28 2. 527. 29 8N 2. 536. 29 N 01-CO 1-Ex. 2-1. Ex, 2,- Product 1. Ex. 2. Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z m/z a mlz f N l Ber N/ N N/ 1. 4916 N 1. 4921 N 1. 4926 2. 538. 3 2. 546. 3 2. 552. 3 N ozon O I O S 0< 0 oA Br Br Br N N N/O v NiN Br N'<NX NeNr/Br Ne, NX fN 1. 4917 2 N 1. 4922 (N 1. 4927 . 540. 3 2. 546. 3 2. 554. 3 bon O O (3 O /v Br G Br w w e N N IJ N NN/ 1. 4918 N 1. 4923 1. 4928 tN 2. 542. 3 b 2. 546. 3 CN 2. 554. 3 N N Cil D Bir Br v Bf B N B N w N N N NN f 1. 4919 k 1. 4924 N 1. 4929 2. 545. 3 2. 551. 3 cl3 2. 556. 31 6N zon zozo H, C N O Ei __ _ s _ A Be 8 Be3 N N N N// 1. 4920 1. 4925 NA 1. 4930 2. 546. 3 2. 551. 3 2. 556. 31 N O S J a tt r N Product 1. Ex 2. Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z m/z ci Cri/ Bu \ \ I er N \ N 1. 4931 (1. 4936 N 1. 4941 6N 2. 556. 31 X 2. 560. 31 2. 566. 31 N V 0 oA 4° o4° C zozos ce N N w Br N Br N N N/ nit BX3 Bt uN/_ ~ t) *~ 1. 4932 N 1. 4937 1. 4942 2. 556. 31 t 2. 560. 31 cl 2. 566. 31 N 0 1 'U 0 G - _ er er WNN/ 1. 4933 N 1. 4938 k 1. 4943 2. 558. 31 2. 565. 31 2. 566. 31 N N O O I S O N- : ca3 er B N ut lu fun 1. 4934 1. 4939 N 1. 4944 3. 558. 31 2. 565. 3 N | 2 566. 31 N N O O O e Br e N N/N N/ zon N 1. 4935 N6 1. 4940 1. 4945 2. 560. 31 2. 565. 31 2. 568. 31 N 0 I W i 1 Ev ? 1 Ex 2 i Ev* ? Product 1. Ex. 2. Product 1. Ex. 2. Product 1. Ex. 2. mlz o, ou CI)) Gr ci Br, Br N \ zon N fun 1. 4946 N 1. 4951 N 1. 4956 2. 570. 31 () 2. 571. 31 2. 580. 32 N N i ON O p \ I O OJ ^S O bu y \ Br v Br N N N/NiN/NiN/ v1 1. 4947 t 1. 4952 1. 4957 2. 570. 31 2. 574. 32 X 2. 580. 32 OS o C° r° a A ci ber Br \ \\N N/ 1. 4948 N 1. 4953 N 1. 4958 9 Br NeN N ; 3 8 e 1. 4948 N 1. 4953 N) 1. 4958 2. 570. 31 bon 2. 576. 32 N 2. 582. 32 ci ci up c a ci I er sr N N/. NN/ N 1. 4949"1. 4954."1. 4959 2. 572. 31 2. 576. 32 S t 2. 583. 32 f J J 1L N N S O //O \ I _.-__. G__.. _. _.-.-_"r _ CA Br N I Br N v \ iN d N N N 1. 4950 NA 1. 4955 ß 1. 4960 2. 572. 31 ?. 579. 32 4° 2. 583. 32 N N fez 0 N cO 0 Product . Ex. 2. 1. Ex. 2. Product Product mZ Product 1. Ex. 2. mlz a a _ i Br Br Br N & 'N \ W BrX O N N/ N-N 1. 4961 1. 4966 N 1. 4971 2. 583. 32 2. 590. 32 (N 2. 594. 33 N F6c o o4°< SckNv a O C N Nq- __T-_-_______ a 7' er/ I i Ar Br NN/ \NN N \ B 1. 4962 1. 4967 N 1. 4972 2. 584. 32 2. 590. 32 2. 594. 33 N O O. /I O i S-f Y G/1 Hr/I G e v Br N 'y Br N x \ N N N N v N 1. 4963) 1. 4968, N 1. 4973 2. 584. 32 2. 591. 3 2. 594. 33 O N CH O C N O o I 1 \/ o bN jazz a~¢~3 Ci si ci \NN S NN/ N 1. 4964 N 1. 4969 (N 1. 4974 2. 584. 32 t 2. 594. 33 O 2. 594. 33 Nl N 0 C, 0 1-P, Q/1 p Bu N NiN \ N NN/ 1. 4965 1. 4970 1. 4975 2. 594. 33 l tN 2. 602. 33 N 'O O p \ F I \p F F \ Product 1. Ex. 2. Product 1. Ex. 2. Product 1. Ex. 2. Product mZ Product m/z Product m/z s v _ Br er Br N\ \ \ \ N) 1. 4976) 1. 4981 N 1. 4986 X 2. 602. 33 (N) 2. 608. 33 D >. 616. 34 oX oA oV3 N N/N N/ N/ _ru 1. 4976 1. 4981 N 1. 4986 2. 602. 33 2. 608. 33 2. 616. 34 N N ru 0 \ pr \ Bv Bv3 B 3 Br N N/ 1. 4977 1. 4982 N 1. 4987 2. 607. 33 N 2. 608. 33 t 2. 618. 34 Ha N O o a N C3 zon N N N-N. 1 up (1. 4979 > 1. 4983 N 1. 4988 2. 607. 33 N 2. 608. 33 2. 618. 34 N N -b _ _... _, _ G/a i ° i Br \N \N-N /N N/ N N O N o--160 cl bu or N_- (N , N N er er e r N 1. 4980 (1. 4985 A 1. 4990 2. 608. 33 2. 616. 34 N 2. 618. 34 N N 1 O O O Sl \/ Product 1. Ex. 2. m/z N'N N N/ N 1. 4991 2. 630. 35 N w _. 0 IN ci, ber N/ N N 1. 4992 2. 464. 26 N OC Cils brun N NiN/ N 1. 4993 2. 532. 29 N zoo 0 Zu N Br N 1. 4994 2. 526. 29 N er a er NN f 1. 4995 c bN 2. 568. 31 0 NU . J tiC TABLE 50 Product 1. Ex. 2. product 1. Ex. 2. m/z m/z _ __ _,. \ \ \ N-N N-N 6 1. 5001 N 1. 5006 2. 476. 26 ON 2. 504. 28 Y y0 cob er er N N-N \ N_N f U 1. 5002 1. 5007 2. 490. 27 2. 506. 28 o ou -N 0' _. _W. N-N \ I N_N \ &N 1. 5003 1. 5008 N s-CH, 2. 496. 27 N 2. 506. 28 Br Sr - Br NN I N-N 1. 5004 1. 5009 2. 502. 28 2. 506. 28 N"'-\Cfia o Br G 8r G N N \ I N-I \\/.-//"/-\// M-N 1. 5005 1. 5010 2. 502. 28 NON 2. 513. 28 Xi 0 0 Product 1. Ex. 2. Product 1. eux. 2. Br CA Br CA 0 $ SNS nu 1. 5011 1. 5016 2. 5'15. 28 2. 524. 29 "\-0 Y 'N HC CH, Bu Br Br N N N 1. 5012 N 1. 5017 N 518. 28 2. 526. 29 s 0. NA3 ci zu 0 Br-... _ C'B CI NS (b SN 3 N-N \ NN \ I N 1. 5013 N 1. 5018 NON 2. 518. 28 2. 528. 29 0 0 0 Br G SNS \ N N-N pN N 1. 5014 N 1. 5019 2. 519. 29) 2. 531. 29 X c O N 0 , N3 Br G Br N-N \ N-N \ N 1. 5015 N 1. 5020 2. 522. 29 2. 532. 29 on 0 S p-CH3/ 1 Ex 2 1 Ex 9 Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z N N N-N \ I N-. N \ N 1. 5021 1. 5026 2. 532. 29 2. 538. 3 OU 0 s p S Br Br -N-N \ v< v< NJ SNS N 1. 5022 N 1. 5027 ON 2. 532. 29 2. 540. 3 O/\ O \ off Br C'Br C' CI a j c - N V U 1. 5023 1. 5028 N 2. 532. 29 2. 540. 3 zon po D ber O Bu S b S b 1. 5024 1. 5029 1. 5024 1. 5029 NtN) 2. 537. 3 N H, 2. 542. 3 \-N 0 \-N \ -N \ NZ Nu c, a -0 Q"y-0 1. 5025 N 1. 5030 2. 537. 3 N p-CH 2. 54. 2. 3. 3 N ON 0 Ex- Product 1. Ex 2. _ Product 1 Ex 2. m/z m/z M/z m/z m/z . _ 4 _ W Un SN b 1 NS 7 N 1. 5031 N 1. 5036 2. 542. 3 N ci 2. 546. 3 c3) NCO 0 Br C'Sr ci CI N-'b Non 1. 5032 N 1. 5037 2 2. 54. 2. 3. 546. 3 ci ° o - CI B CI C \-N N-N N 1. 5033 N 1. 5038 2. 544. 3 2. 551. 3 ON s ON 0 '0 ber Br C sr Non N_N \ N-N \ N 1. 5034 N 1. 5039 2. 54. 4. 3 2. 551. 3 N N N O N Mut Cbz pu N N N-N \ I 1. 5035 2 1. 5040 N. 546. 3 cri /\ I Y Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z Br C B CI S b-&N b \ I 1. 5041 N 1. 5046 2. 552. 3 2. 556. 31 N 0 0 0 0, 0, ex ci cl N- NU 1. 5042 N 1. 5047 ON 2. 552. 3 NAH, 2. 556. 31 N CH3 ci o'O NON dz N N \ N-N \ I 1-NS 7-NS N 1. 5043 N 1. 5048 N 2. 552. 3 ON 2. 556. 31 tN oKOW J"c. 'f c 0 \/ S 7-NS b \-N C \-N N 1. 5044 1. 5049 ON CH., 2. 552. 3 2. 558. 31 . a S 7 SN 7 bu \YIN \ b _nu N 1. 5045 N 1. 5050 2. 554. 3/cl3 2. 558. 31 /)/ s N H _.. 0 O Product 1-Ex. 2. Product 1. Ex. 2. m/z m/z , N. _N \ I N-N \ N 1. 5051 N 1. 5056 2. 558. 31 / 2. 566. 31 CH3 0 0 0 __. ____ B CI __. _.. _. ___. __.-___ _. __.- ___ __ \ N ci N-N NON N 1. 5052 N 1. 5057 2. 560. 31 ON 2. 566. 31 a o G O NZ zon N 1. 5053 N 1. 5058 S b SNS 2. 562. 31 2. 568. 31 ON ON /\ 0 Br ber (\N \-N , N-N \ N-N \ N 1. 5054 N °x\ 1 5059 2. 562. 31 2. 569. 31 o o ON SNS a a cl 1. 5055 1. 5060 ? 2. 565. 31 0 2. 569. 31 0 it N C- c 1 Ex 7 1 Px7 Product, Product,'" m/z m/z ber C' czar 1. 5061 2. 576. 32 ON N 0 / 0 0 //Cli O er ci Br ci v N ; b I-N N-N \ N-N \ 1. 5062 1. 5067 2. 570. 31 2. 576. 32 N o/\ o d/\. _ 0 \YN \ < \--N N N-N \ 1. 5063 N 1. 5068 WO 2. 570. 31 2. 577. 32 / \ CH3 0 o Br MC Br CI N N N N-N \ S 7 SS N 1. 5064 N 1. 5069 DN 0 2. 570. 31 2. 580. 32 O FF F R _ B a _ 0 F F Un N-N \ -nu N 1. 5065 bon 1. 5070 ci 572. 31 Npo 2. 580. 32 ci ON F Product 1. Ex. 2. Product 1. Ex. 2. product m/z bof t Cb N N N6N Non 1. 5071 1 5076 2. 2. 580. 32 N 1 50762. 588. 32 o C, CI Br i... \ ci 1. 5072 1. 5077 2. 580. 32 2. 593. 33 0 O O/FijC SNS er 50' N N N N-N N-N N 1 5073 2. N 1 5078 2 a 580. 32 Nc 593. 33 N/ N-JN N 8 G Br A zon Cl N 150742. N 1. 5079 ! N) < 1 5074 2. | | SNa 1. 079 X G 580. 32 2. 594. 33 ON N OS cl err N N -N N-N N 1 5075 2. N 1. 5080 588. 32 2. 594. 33 N-0 ON 1 Pv 9 1 Pv * ? Product 1 Ex. 2. Product Ex. 2. m/z m/z Br Br Cb 11 N N-N \ I pN b 1. 5081 N 1. 5086 ZON Nv 2. 594. 33 tX 2. 602. 33 &b 0 Ber \ N N-N N-N 1. 5082 N 1. 50872. bon 2. 594. 33 N 0 604. 33 N six ce ce ci ci C \YN Ber a N_N \ 1. 5083 N 1. 5088 t 2 59433 t 04 2 604. 33 v -N \ // CI Br ci t SNS SNS CL N U 1. 5084 N 1. 5089 2. 595. 33 2. 604. 33 0 \ o o i o/ SS Se \YIN N N \ N-\ \ I 1. 50852. 1. 5090 602. 33 2. 604. 33 o. I d/\ os Product Ex. 2. m/z r bu non N 1. 5091 2. 616. 34 ZOO 0 Cl \ N-N 1. 5092 NON 2. 450. 25 -N. N nu O bu (\ N 1N-N 1. 5093 2. 518. 28 ON 0 Br ci \ 1. 5094 2. 512. 28 ON C, Ci \ y 1. 5095 2. 554. 3 0 cet H, C tc TABLE 51 1. Ex. 2. 1. Ex. 2. 1. Ex 2. Product 1. Ex. 2. Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z m/z N N ci a N 1. 5101 N 1. 5106 N 1. 5111 2. 448. 8 2. 476. 8 2. 490. 8 Nt X S p N O N 0 6 a I Br N g N\ \ I zon a e, G NN e N 1. 5102 Nn 1. 5107 a 1. 5112 2. 462. 8 2. 478. 8 2. 494. 8 0 T L X 0 N N 0 oo IC., ... \ \ 1 Br... N.. \ I...... _.. 1 ci /O G /CI N 1. 5103 No 1. 5108 Nz 1. 5113 2. 468. 8 2. 478. 8 2. 498. 8 % E X n 6"0 C14, B cul "ll..--N ( 1. 5104 N 1. 5109 Nl 1. 5114 2. 474. 7 neo 2. 478. 8 N ° 2. 503. 8 cl% N a 4cC v t. < by° b'° b ?" \NG \NG ( : 1 r, 1. 5105 r, 1. 5110 N 1. 5115 2. 474. 7 2. 490. 8 2. 504. 8 N O N O N O 0 66\ Product 1. Ex. 2. Product 1. Ex. 2. Product 1. Ex. 2. mlz mlz mlz v w _ C, , N N N 1. 5116 N 1. 5121 1. 5126 1. 5126 2. 504. 8 2. 514. 8 0 2. 524. 8 O N p N 0-cit ber 1 s \/ cul Br Br N\ Br \ w Nz 1. 5117 1. 5122 N 1. 5127 2. 504. 9 2. 514. 8 2. 524. 9 X C0, 8 CH3 I/ 'N il vl NI a rtN N/ er N 1. 5118 N 1. 5123 N 1. 5128 2 neo 2. 510. 8 L 2. 519. 2. 524. 9 N CI I o I ___ » _-____ ___ __ _.-- Br N 1 Br N 1 er w w /G f C J N 1. 5119 N 1. 5124 1. 5129 2. 512. 8 S 2. 519. 2 ß 2. 524. 9 0 ci .."w Hc //G 1/ er er f NN/ 1. 5120 1. 5125 0 2. 512. 8 1. 5130 2. 523. 8 NdiO 2. 526. 9 N FiC W U W .. _ Product 1. Ex. 2. Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z m/z m/z B, Q Br Qa Br X \N N A /N O CJ N S. CI N N N N 1. 5131 (1. 5136 1. 5141 2. 528. 8 2. 552. 8 N 2. 567. 8 0 ber N J- Br \ B \ I N N v w G N/N G/ 1. 5132 1. 5137 N 1. 5142 2. 530. 9 2. 553. 7 N ° 2. 574. 9 p N O Cl ci rA i1 I il CA ci N N, G e G/CI N 1. 5133 Nm 1. 5138 Nz 1. 5143 A- 2. 534. 8 2. 553. 7 2. 576. 9 N N 0 CA CA 0-0 Br / I r G s I/ G er N\ er I ar r/a \N N G 1. 5134 N 1. 5139 X'1. 5144 N 2. 538. 9 2. 560. 9 N 2. 576. 9 N 0 I I, i\ il il Br Br 8y B but wo N N 1. 5135 N 1. 5140 1. 5145 g 1. 5135 Nz 1. 5140 Na 1. 5145 2. 552. 8 2. 566. 9 X 2. 514. 8 O N N O FF/ I/w Product m/z Product rn/z Product rnk mlz m/z m/z m/z Nz B Br NN/C N/ N 1. 5146 N 1. 5151 Na 1. 5156 2. 485. 8 2. 519. 2 2. 534. 8 N 0 N6 nu I N Ci v B Br Br ci N 1. 5147 N 1. 5152 Na 1. 5157 2. 491. 8 2. 523. 8 N ° 2. 540. 9 N oW g A p ."'i cl C, N CA v w N N, N N N N N 1. 5148 Na 1. 5153 1. 5158 2. 509. 8 2. 528. 8 2. 541. 8 N O w w o ou oo ber ."c°. co N - ( e a 1. 5149 N 1. 5154 W 1. 5159 2. 509. 8 2. 530. 9 2. 541. 8 X SSCA N N WJ °Ys nu B NU Br N I Br \ I Br '.......... a 1. 5155 1. 5160 2. 514. 8 2. 530. 9 Xi i o S \ I TABLE 52 Product t. Ex. 2. Product 1. EX. 2. m/z m/z Br N Br N G/N CI N N 1. 5201 N N 1. 5206 2. 462. 8 2. 490. 8 Nz O O er, /' CI 1 C, N., N N 1. 5202 N N 1. 5207 2. 476. 8 2. 492. 8 zon cl Br G I Br N B 1. 5203 N 1. 5208 -1N 2. 482. 8 2. 492. 8 N ks-cA ?"h n n . _. _" _ / Buzzer cri -N. N \NN/ No N 1. 5204 Na 1. 52009 2. 488. 8 2. 492. 9 N CHEZ oh p PC, ci Br Br CA G \ N \ N e N N 1. 5205 N N 1. 5210 2. 488. 8 2. 504. 8 N /S O Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z s Br-N Br CA p ci N N 1. 5211 N 1. 5216 "\ 2. 504. 8 2. 518. 9 N 0 O N 0k pu, ci ci u- ! - ci N N N 2. 5212 N 1. 5217 2. 508. 8 2. 518. 9 ol o o cil O O E3r N_- PU, cri _ BU CI j N CI N 1. 5213 N 1. 5218 2. 512. 8 2. 524. 9 0 1p. -.-- C, Br N er N'-/ N Nm 1. 5214 N) 1. 5219 2. 517. 8 2. 526. 9 N 3 c6 N C 0 O H, C Fisc but -n w --n z Cl N N N 1. 5215 1. 5220 2. 518. 9 2. 526. 9 N N O 6 0 Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z -- Br CI N G / N 1. 5221 N 1. 5226 2. 528. 8 2. 538. 8 0 0 N N n n N 1 Br N\ Br N\ NiN/NiN/ N 1. 5222 N 1. 5227 2. 528. 8 2. 538. 9 N Br O w o \ a cri ex Ci NN S N-N 1. 5223 N 1. 5228 2. 533. 3 2. 538. 9 N 0' 0 ber / sur ci cl 1. 5224 N 1. 5229 2. 533. 3 2. 538. 9 "N Br\ N Br Cl N IN _. er N e \ iN/G \ N/G N N 1. 5225 1. 5230 2. 537. 9 \N 2. 540. 9 N 0 N Product t. Ex. 2. Product 1. Ex. 2. m/z MHz 1 1 Br N Ar ce a \NN e \ N e N 1. 5231 1. 5236 CF6 2. 542. 9 2. 566. 8 N h52 %"2 ?... O 1 O 1 N R,. bu 1 ex CL ce zon N 1. 5232 N N 1. 5237 YoVt 2. 544. 9 2. 567. 7 cil Bu ber O 1 cl 1 1 Br N' Br CI N 1. 5233 N 1. 5238 2. 548. 9 2. 567. 7 CI Zea rif w C, ........ _... _. __ Br N\ Br N w G a NiN/\ iN e N N 1. 5234 N N 1. 5239 2. 552. 9'oX 2. 574. 9 0 Sur O w O ci CRI NiN N/ N Na 1. 5235 1. 5240 2. 566. 8 2. 581 N N OF 1 O F F v Product 1-Ex. 2. Product 1. Ex. 2. m/z m/z sr N\ er bu ber \NiN/\NiN N 1. 5241 N 1. 5246 2. 533. 3 2. 548. 9 ta oW 0 Su N cl N 1. 5242 N 1. 5247 N) 1. 5242 N 1. 5247 2. 537. 9 2. 554. 9 N /N O a cri _ _ Br'N gr N w nu 1. 5243 N 1. 5248 2. 542. 8 2. 555. 9 N N o. 0 O w 1 O w 1 C' N 1. 5244 N) 1. 5249 1. 5244."1. 5249 /CF6 2. 544. 9 2. 555. 9 ZON 0 N /1/1 N N /o \Y v Na 1. 5245 Nm 1. 5250 -1N 2. 544. 9 2. 574. 9 N N w Cbz Product 1. Ex. 2. Product 1. Ex. 2. mlz mlz r 1 N N, N BrN/ a 1. 5251 nu 1. 5256 2. 579. 9 2. 501. 8 N o o ItC 0 6r Bu G N NN l-e 1. 5252 N 1. 5257 2. 579. 9 2. 514. 8 W N N N-N N-N 1 ar Br CI CI ci Nz Br 1. 5253 N 1. 5258 Na 1. 5253 N N 1. 5258 1 2. 581 2. 518. 9 , N -h s----- i 1 13r\ N yH/ 1. 5254 1. 5259 X 1. 5254 Nz 1. 5259 cor 2. 588. 9 2. 530. 9 S oS / cri nu N N \ iN e 1. 5255 1. 5260 2. 590. 9 2. 530. 9 0 0 Product 1. Ex. 2. Product 1. Ex. 2. mlz mlz m/z m/z " \ (J ( ci 1. 5261'\ 1. 5266 2. 538. 9 N 2. 556. 9 N CH o0 o 1 1 NIT 0 ____. _____. _________.... ___ . a, a \NN CNx 1. 5262 Wf 1. 5267 2. 542. 9 2. 556. 9 b to 0 lo 0 1 v Br N N cl NiN 1. 5263 N 1. 5268 2. 547. 3 2. 537. 9 N O o cl Ber B a CA NiN N N 1. 5264 N) 1. 5269 2. 551. 9 2. 566. 9 -C -Ho N N w WN O O 1 - Br N Br w G NN / 1. 5265 nom 1. 5270 2. 552. 9 2. 581 N i N 0 O 1 Ex ? 1 Ex ? Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z N_- Pu, cl CI N N \ iN e. 1. 5271 Na 1. 5276 2. 581. 7 2. 559. 3 N jazz N N a er N ar NN a NN 1. 5272 1. 5277 2. 581. 7 N 2. 562. 9 osa a ob cl/ a / /,/1 sr ar G/_-1 C N O N N 1. 5273 N N 1. 5278 2. 588. 9 2. 556. 9 N \ N 0 0 o er N Br v N/\ G N 1. 5274 N N 1. 5279 2. 602. 9 2. 499. 8 °9- o N ci r 1/o d / Br N' BI NN O G \ N O 1. 5275 N 1. 5280 2. 510. 8 2. 499. 8 c'N 0-C N O I oN TABLE 53 7 Product 1. Ex. 2. Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z m/z B, Br Br Br/I Br W N N W N Be 1. 5301 1. 5306 box 1. 5311 2. 434. 7 2. 462. 8 Nl 2. 476. 8 N N N °o o Bu ber N Bu sur 8 Y 1 N NAG N 1. 5302 1. 5307 N 1. 5312 2. 448. 8 2. 464. 8 oR 2 480 8 N Nz N A Ly Br Ber N ex Bu w W \ N/G NN/G N/ N-N 1. 5303 N 1. 5308 N 1. 5313 2. 454. 8 2. 464. 8 2. 484. 8 N N ou S-cit ber oYo t N N-N N N Nu w N/G \\ iN G N'1. 5304 Nz 1. 5309 N 1. 5314 2. 460. 7 2. 464. 8 2. 489. 8 N 1-if N o 1 on O CH, W //I i Br I Br er s N- iN a NiN a 1. 5305 1. 5310 N 1. 5315 N 2. 460. 7 N 2. 476. 8 N 2. 490. 8 0 01-C-0 U Product 1. Ex. 2. Product 1. Ex. 2. 1. Ex. 2. Product m/z m/z mlz er/I er -N ci \NN G N 1. 5316 N 1. 5321 N 1. 5326 2. 490. 8 1 N 2. 500. 8 2. 510. 8 0 N 0 s 0 B,----------- ci Bu Br \\ N CI w N N/CI ! 1. 5317 N N 1. 5327 N 1. 5327 N 2. 490. 8 N 2. 500. 8 o coo N 6c, o i Bf N Bf Bf a Br CI Nt) B B NoNH N N a 1. 5328 N 0 2. 496. 8 2. 505. 2 2. 510. 8 ° N I 0 O/I. Br Br N\ Br N Bu G ("1. 5319 N (N 1. 5324 NN/ f I. 5324 N N 2. 510. 8 r4, c o/'o N 0 o G \N rua Br Bf \ Br v \ N Q N N/G N f X 1. 5320 N 1. 5325 (N 1. 5330 2. 498. 8 N 2. 509. 8 N 2. 512. 8 o N o K,) o Product 1. Ex. 2. Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z m/z i I i I Er N roi N N N 1. 5331 N 1. 5336 1. 5341 2. 514. 8 N 2. 538. 8 o N o 2. 553. 8 o U F D 'CHa O I/O N O Off ber cl N- \ CI N N/ N 1. 5332 1. 5337 N 1. 5342 2. 516. 9 N Cl 2. 539. 6 2. 560. 9 N CI/ As oe, A N 6 N Br Br Br fV N \ N N G N N G \\N G N-N C3 1. 5333 Na 1. 5338 N-N N 1. 5343 N 2. 520. 8 cl 2. 539. 6 ) j, t) 2. 562. 9 N 0 0 ou o I I o G t Br Br Br N N N w w i w /G /G /CI N 1. 5334 N-NN 1. 5339 N 1. 5344 2. 524. 9 X Ç | 2. 546. 9 2. 562. 9 N N N O O \ I O w I, O \ I Br N \/N \ er N v \/N W N- N N/G NN d N N/ Nn 1. 5335 f 1. 5340 2. Nn 1. 5345 N 2. 538. 8 N 552. 9 N 2. 500. 8 o OF I//\ Fi 0-0 J'U Product 1. Ex. 2. Product 1. Ex. 2. Product 1. Ex. 2. m/z rn/z m/z m/z m/z m/z MHz Br] 3r Br N N C N N N/CI bu 2. 471. 7 J 2. 505. 2 2. 520. 8 N N o i I/ o // PU, ci cri CI \ N/G N N N 1. 5347 N 1. 5352 N 1. 5357 2. 477. 8 N 2. 509. 8 2. 526. 8 N N oye 0 r 0 S cl er N\ 1 Br/ Br N \ N cl a w \\ N CI 1. 5348 N 1. 5353 N N 1. 5358 2. 495. 8 2. 514. 8 XN j 2. 527. 8 0 N N 0 0 N 0 y i 0 CH, Br I gr _ I ar v W N \ Nw W \N-N I \-- N N 1. 5349 N N 1. 5355" 1. 5359 2. 495. 8"1 2. 516. 9 N 2. 527. 8 01-1 O I/O ''N \ N O-''W //1/ er I Br er N \ w w B \N-N--er' N 5350 1. 5356 N. 500. 8 J 2. 516. 9 N 2. 546. 9 N N j O I/, C O hoS Product 1. Ex. 2. Product 1. Ex 2. Product 1. Ex 2. M/Z m/z m/z Br Br Br - p ci N-N _ (/, N-N N N 1. 5361 N 1. 5366 Na 1. 5371 2. 551. 8 2. 473. 8 N 2. 510. 8 9 N CF 0 0 c H, c i i Br I g Br v w N wI _ v w ci ci N N 1. 5362 N 1. 5367 Nx 1. 5372 2. 551. 8 N 2. 486. 8 2. 514. 8 o ON N zu i I i I i I 6r g 6r \NN/G \ N/G N N/G nu 1. 5363 N N 1. 5368 N 1. 5373 2. 552. 9 2. 490. 8 N 2. 519. 2 N \ O B bu G w N N-4- N-N bu \ \ CI si-0 BX, Ji3 B Be r q < ? 1. 5364 N 1. 5369 N 1. 5374 oS 2. 560. 9 1 2. 502. 8 2. 523. 8 N a 0 N Sur ber ci i i e Br N N-N M 0 i B Nk, NS B NS, NS B Nk, Nd 1. 5365 N 1. 5370 N 1. 5375 ion 2. 562. 9 2. 502. 8 2. 524. 8 N ou 0 1. Ex. 2. 1. Ex. 2. 1. Ex. 2. Product mZ Product mZ Product m/z ' l Br BNN a \ _I \ er v y i N ! i aN t B' 1. 5376 1. 5381 1. 5386 2. 528. 8 2. 553. 7 N 9 531. 2 G I i a G ........ _......-__. er er N ci N-C' Zig /CI N 1. 5377 X 1. 5382 N 1. 5387 2. 528. 8 2. 553. 7 2. 534. 8 O p /O C'a O W I G a ci ci bu N-N N-N N N Na | 1. 5378 N h 1. 5383 N N 1. 5388 2. 509. 8 2. 560. 9 IN 2. 528. 8 N v N 0, cl N 1. 53 N N N/G N N CI 79 1. 5384 N 1. 5389 2. 538. 9 N 2. 574. 9 N 2. 538. 8 i o 0 o I oi o \/' i i I. i I i Br e Br ci \ N G v CI N /CI N 1. 5380 N 1. 5385 N 1. 5390 IN 2. 552. 9 N 2. 482. 8 N 2. 471. 7 0- a o 0 0 N TABLE 54

1. Ex. 2. 1. Ex. 2. 1. Ex. 2. Product 1. Ex. 2. Product 1. Ex. 2. Product 1. Ex. 2. Br\ Br \ pp m/z m/z m/z zig CA ci 1. 5401"N 1. 5406 N 1. 5411 2. 463. 3 2. 491. 3 2 2. 505. 3 6c HC NC S pu, ci N-B N Br N v Br CI CI N N 1. 5402 N N 1. 5407 N 1. 5412 j 2. 477. 3 2. 493. 3 Z 2 509. 3 FCIN N-cli N tiC 0 ° o R r v l N N N N'N G G/ tJ r W N d ri N 1. 5403 N 1. 5408 2. 483. 3 2 2. 493. 3 f 2. 513. 3 O N O htjC \ Q d /1 v 1/\ Bu ber N\ G CI ar nL \ iN \NiN/ N I BrNdnf 1. 5404 N N 1. 5409 N N 1. 5414 2. 489. 3 2. 493. 3 2. 518. 3 o ( u C, Cit /CH2 time zon ,, r, B, Br a N\ NA G \/N G/ N-,--\ N 1. 5405"N 1. 5410 N 1. 5415 2. 489. 3 2. 505. 3 2. 519. 3 . N O N (O o hlC hlC \ l\t s Product 1. Ex 2. Product 1. Ex 2. Product 1. Ex 2. m/z m/z m/z 1''1 ci CI N N N N N 1. 5416 1. 5121 1. 5426 . 54. 26 2. 519. 3 2. 539. 3 N O oN H, C s U S n n n Br Br Sr N_- ci CA Br Br N Br G G NiN d NiN N 1. 5422 1. 5427 N 1. 5417 Nm 1. 5422 N) 1. 5427 2. 519. 3 ßN ° 2. 529. 3 0 2. 539. 3 N C' -s HIC Cl, cl, -. . _.... ci er N ar ci CI iN'd ( e N \NiN ' Na 1. 5418 N 1. 5423"1. 5428 o 2. 525. 3 2. 533. 3 2. 539. 3 HaC G O C C C --u- n n n Br &, NX Br uNoN N$ Br ; 2NoN NX N N 1. 5419 N 1. 5424 nom 1. 5429 2. 527. 3 2. 533. 3 2. 539. 3 Q N O N O H3CX Ca 5 O 0---------0-8--s 1 1 \ er N er er p-PC, N Nz N Na 1. 5420 Na 1. 5425 Na 1. 5430 2. 527. 3 2. 538. 3 2. 541. 3 NC, N 0 6c Nc, C Product 1. Ex 2. Product 1. EX 2. Product f 1 m/z m/z m/z - _ _... r r p-IC er N-a er'L a G \N N N N N N N N Na 1. 5431 < 1. 5436 9 1. 5441 H 2. 543. 3 2. 567. 3 2. 582. 3 I r v o I% C F F T-Br N ar P, N 1 B N\ Br N \ N d Na | 1. 5432 N N 1. 5437 Nz 1. 5442 2. 545. 3 2. 567. 3 2. 589. 3 b 3eli Q Ha3 FIC a e / /\/1 er e N er ci cr a PC I P, N 1. 5433 Nm 1. 5438 N 1. 5443 2. 549. 3 2. 67. 3 2. 591. 3 , N O v Br N Br O d//a, / n n C3 1 \ a G N d N Na 1. 5434 N N 1. 5439 S 1. 5444 1. 5439 N-1-) 1. 5444 ° 1 C9 n n 1 m / _ ____---w, i \ i 1 Br N-G 6r N 8 N v G G N I fJ N d 1. 5435 N N 1. 5440" 1. 544. 5 2. 567. 3 H3C 2. 581. 3 c 2. 529. 3 N O HC N F , S 1 F v Product 1. EX. 2. Product 1. Ex. 2. Product 1. Ex. 2. mlz mlz mlz mlz 1 i r mlz Br Br NN NN/ N 1. 5446 Na 1. 5451 1. 1. 5456 2. 500. 3 2. 533. 3 2. 549. 3 CIN N-CH H3C S C \ B sur N \-/ G Br N Br N er W a W n n s n N Nm 1. 5447 Nm 1. 54525 Na 1. 5457 N-,--\ 2. 830. 5 2. 719. 4 N o 2. 555. 3 S aN 5S 1''aC HoC W S pa pa ci ci CA IN N \ N N NN/ 1. 5448 1. 5453 nu 1. 5458 12. 524. 3 2. 543. 3 0 2. 556. 3 'H, c H, c'' N e p hic . l _ 0 1 r 1 S t . y \ N G \ N N N \ N N N < 1. 5449 N o 1. 5454 X 1. 5459 2. H3C X 2. 524. 3 2. 545. 3 gNb 556. 3 1 i W Ci v--5 n n n ____ Br Br er G d G NN d NnN e \NN/ 1. 1. 5450 N 1. 5455 N 1. 5460 0 IN 2. 529. 3 2. 545. 3 I% eN 0 Q 9 W NC Nc zu Product 1. Ex. 2. Product 1. m/. 2. Product 1. Ex. 2. E=x 2, m/z n n e3 Br \ 1 r 1 Br B N v er Cl cri a N N 1. 5461 N N 1. 5466 N 1. 5471 2. 580. 3 2. 502. 3 0 2. 539. 3 zon sN O/N O HaC 14, C N-'IN F6c H3CNC O mm-v e _____ tir Br B v C' NiN N NiN G \NN/ 1. 5462 1. 5467 S 1. 5472 ° 2. 580. 3 0 2. 515. 3 < 2. 543. 3 N_N 9\ O 6"1- \//\o Br, r er 6 N w sr v O Co M NiN G G NN 1. 5463 N 1. 5468 N 1. 54. 73 X o 1. 5463 Nn 1. 5468 Nm 1. 5473 , C, N 2. 581. 3 S 2. 519. 3 S o 2. 547. 3 '- a w e G N N \ Br N Br N Br CI CI G cl Z'N 1. 1. 5464 Na 1. 5469 1. 5474 2. 589. 3 0 2. 531. 3 N o 2. 552. 3 H, C H3C X N N /v N_- "\ 4 zu er er er N. N r a N^ G N tJiN/IJN/ N 1. 5465 1. 5470 N-1 1. 5475 tC, 2. 591. 3 2. 531. 3 0 2. 553. 3 N O , J C C i i 9 O Product 1. Ex. 2. Product 1. Ex. 2. Product Ex. 2. m/z m/z Or N cl Or n N Br N Br N er a 1. 5476 N 1. 5481 \ N G \ N / 1. 5476 N N 1. 5481 2. 557. 3 2, 581. 3 54862. Ft, O Cl y > 1 O G-o 1 w N- Br N Br N er G G1 NN \ N G N, N NON_ 1. 5477 N. 1. 5482 1. 5487 2. 557. 3 2. 589. 3 o 2. 891. 5 F6c, 891. 5 a Br,, N a N n n n o, 6r N\ N N CI \ G Na 1. 5478"1. 5483 N N 1. 5488 N 2. 538. 3 __I 0 2. 500. 3 N (\p c'NSo N Hic // Br a N_- N= (") =<''\ /\ 1/ er Br Br N-I G N \ N /1. 5479 Na 1. 5484 N N 1. 5489 2. 567. 3 o 2. 559. 3 2. 500. 3 N 6c fisc ber Zon in a a Br N- N (-N' N N IN 1. 5480 N 1. 5485 1. 5490 2. 581. 3-,--\ 2. 563. 3) 2. 501. 3 0 IN_/ à B G \ N TABLE55 Product 1. Ex. 2. Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z m/z m/z CA a Bw Xg e B¢\WNX N-N N-N N-N 1. 5501 N 1. 5506 N 1. 5511 2. 488. 81 2. 516. 87 2. 530. 87 s I II N II N \ I N N N XNt XNt 0 0 0 a a a Br I Br I Br I \ y v \ N_NoS N_No+J N_NoS 1. 5502 N 1. 5507 N 1. 5512 2. 502. 84 2. 518. 84 2. 534. 84 0 Br < Br \n Br Y AN 0 p ci Br Br Br y v \ y NN N N I NN 1. 5503 N 1. 5508 N 1. 5513 2. 508. 87 2. 518. 84 2. 538. 87 0 H3CI om (S n O O \ I O ci a Br I . I \ er 0 0 o--oy ci CA N-N.-N N-N N 1. 5504 N 1. 5509 N 1. 5514 2. 514. 81 2. 518. 88 CH, 2. 543. 85 chu fez BrI Br Br I b l < 0 6 C o \N N N N-N N-N N-N 1. 5505 N 1. 5510 N 1. 5515 2. 514. 81 2. 530. 87 2. 544. 9 0//-s O k f _ zu O O O 1. Ex. 2. 1. Ex. 2. 1. Ex. 2. Product 1. EX 2. Product 1. Ex 2. Product | 1 Ex 2. m/z m/z m/z B<l Be B G v I N N/ N 1. 5516 N 1. 5521 N 1. 5526 2. 544. 9 CF6 2. 554. 87 o N ql : rN6 0 0 0 O r N N cri 'ex i y y/N I/y i /\\N/N N/ ! s o o o B S +1 Be ! Be N 1. 5517 H3C N 1. 5522 1. 5527 2. 544. 92 2. 554. 87 o N 2. 564. 91 i I W o o O t G bu r N-N 1. 5518 N 1. 5518 N 1. 5523 N 1. 5528 2. 550. 89 2. 559. 29 2. 564. 91 i a 'N 0 \ I N/N i ouzo O ci C' Ber \ \ N i i/N N/NN/ 1. 5519 1. 5524 1. 5529 2. 552. 9 N6 2. 559. 29 O%, NJ 2. 564. 91 Nu : I' ° c _..-_ Br I g a er B@ ; , ', /NiN 1. 5520 N 1. 5525 S 1. 5530 1. 5530 \/ N, N " xi i Product 1. Ex. 2. Product 1. Ex. 2. Product Ex. 2. m/z m/z m/z Be WS Bv Br Br N/y w \/ N-N N N NN i N N 1. 5531"1. 5536 1. 5541 2. 568. 9 2. 600. 95 1. 5541 N 0 N 0-r 0-"Y 01-0 B Sr Br N-N N-N W NsX Bw NsX Be NsX N N-N N 1. 5532 N 1. 5537 N 1. 5542 2. 574. 91 2. 606. 99 2. 525. 83 N \ I N/I N \ I N ci oX N N tJ/N N i N NON 1. 5533 N 1. 5538 A 1. 5543 0 N6 2. 578. 94 9 d 2. 614. 97 ans. 581. 9 N coo ° A > o ; % my Br -N ;-y N i N/ N N/N N// N N 1. 5534 1. 5539 N 1. 5544 2. 592. 85 N6 2. 616. 95, 2. 581. 9 0 te lull I /N o O/N F F F O I I O N Br G B\ _w Br a \ yyI, w N N 1. 5535 A 1. 5540 1. 5545 2. 592. 85 0. 6 2. 616. 95 2. 605. 92 F I \ i nez /N o-NN FX N, O I O Product 1-Ex. 2. Product 1. Ex. 2. m/z m/z C'cl Ber / N N N N) 1. 5546 N 1. 5551 2. 573. 32 2. 525. 83 N N _ X o i Cl cl bu ber Br G I Br G \ i r N N/N N/ 1. 554. 7 1. 5552 N 2 582. 88 2. 526. 82 fun N O \ O O Br'a er ci N4Nt Sur Nz N-N N-N N 1. 5548 1. 5553 N 1. 5548 A 1. 5553 2. 607. 76 HaC4O. 573. 92 ! ! , I NZ ber N-N Br i N 1. 5549 2. 607. 76 _-,, N r Cl Cri Br / N/ N 1. 5550 2. 536. 86 Fc 0---y N6 0 TABLE 56 1 Fy 9 1 Fy9 Product 11. Ex 2. Product 1. Ex 2. m/z m/z sur (-0 nu . ils\ N-N 1. 5601 1. 5606 2. 481. 26 N-2. 548. 3 N N zu brrr E3r N' 1. 5602 1. 5607 er N Br N O 1. 5602 1. 5607 2. 495. 27 N-N Nß N N N I o. 6 o er NsO NI 1. 5603 1. 5608 N-2. 535. 29 2. 554. 3 N Br N-V0 N_ 0 / N\ I I e O go 1. 5604 B, \ a 1. 5609 2. 2. 543. 3 VJ 2. 555. 31 N N N / N. I N. 5610 . ___ IA Is 1. 560'5 o 1. 5610 u M _N J 2. 543. 3 2. 559. 31 N N 6 6 N\ I N\ I 1. Ex. 2. 1. Ex. 2. Product m/z Product m/z F F 1 J F N'N'% o s 1. 5611 1. 5616 N_Nsg 2. 565. 31 vu 2. 579. 32 N // N\ I N\ I 0 F F Br NS F F ° N \ \/ 1. 5692 2. 565. 31 1. 5617 NU Nw i Nw I Cl-o F 1 G SO SO Br Br N \\ N 1. 5613 2. 565. 31 N N N I N\ I GAZ zozo S Br I F s 0 1. 5614 N F F 2. 569. 31 N i N I Br'S N N /B wNi N N 1. 5615 N F 1. 5620 2. 571. 31 'F'' N / N I N Product 1. Ex. 2. Product 1. Ex. 2. mlz Q1 0 F Br Nis w zu bu Nz c'6 1. 5621 1. 5626 2. 615. 34 2. 547. 3 Nu Nu 0 N O N bar ? \v 1. 5627 2. 680. 37 \\N_Nf 2. 547. 3 NA NI I N\ I Br N-S\o N r e S\ o _ y N O N-N 1. 5623 N-N 1. 5628 2. 529. 29 N 2. 554. 3 N N vso ß _. _. CHs FIC 6r S\ p 1. 5624 Br, N 1. 5629 2. 543. 3 2. 555. 31 N N N // N\ I NW I po F o N'-0 bar N-V 1. 5625 1. 5630 Br S v° <Nsr, O 1. 5625 S <, s\=° 1. 5630 2. 559. 31 N N N N I N I Product 1. Ex. 2. Product 1. Ex. 2. m/z /z F/F w f o S, o (N fuzz N/\O O 1. 5631 1. 5636 N-Nvl 2. 561. 31 2. 565. 31 N a N I N I /a \// N \\ SO p Br 1. 5632 r-N_ 1. 5637 2. 563. 31 N_Nf 2. 579. 32 cl N Sr s N\ I N\ I O\ i0 N, /CI Br N/O F 1. 5633 F 1. 5638 N-NU N I _ __________ . _.. N N 6 6 _o S o . S sr 1. 5634 0 1. 5639 N 2. 563. 31 N_N N 2. 581. 32 N N I/ N\ I N\ I \ 1 F N _.. _ o N o . N C'a N 1. 5635 N-N CF6 1. 5640 N-N 2. 563. 31 N) CC % 2. 585. 32 N N N MEx. Product 1. Ex. 2. Product Ex. 2. m/z m/z __ O O B NiSi bu \ \ \ r-N_ ON N 1. 5641-N N-N 2. 587. 32 N F 1. 5646 NEZ I NAZI O 1 SOOCIia 1 OG Br N NSO Br 0 1. 5642 1. 5647 2. 589. 32 Nz 2. 597. 33 N N 0, Cbz cri H, c w o. e a t {'YC ! er N/\\ o r 1. 5648 N N ? 2. 589. 32 N_Nf 2. 597. 33 N N ruz N I N Q_ G w I/0 1 r G -S 0 Ber\ 0 rN_ 1. 5644 1. 5649 2. 593. 33" 2. 597. 33 N N \\ 10 N\ I N\ I O\ ii0 G Br NS F w N fuzz Nu 1. 5645 N 1. 5650 2. 597. 33 N_N N 2. 597. 33 N XI N Product 1. Ex. 2. Product 1. Ex. 2. i X - ro, d Ct bu zon ex 1. 5651 NN s 1. 5656 2. 597. 33 H, C 2. 607. 33 N 0 Nw i Nw I Br /sr N Nt / B N/SO NN 1. 5652 ' 1. 5657 \ 2. 599. 33 N_N N 2. 607. 33 N N cul 6 S ci 1 w s e N'S. o o e 1. 5653 1. 5658 2, 603, 33 2. 607. 33 N N // Zon \ O er NS Br NN/ N-N 1. ! 5654 N-N 0 1. 5659 2. 605. 33 N 2. 621. 34 N, N J N Br NS SOO Br I /\ F 1. 5655 N"N 1. 5660 2. 607. 33 N F F 2. 631. 35 R i N N I

Product 1. Ex 2. m/z axa cl zig bu 1. 5661 N_Nsr 2. 631. 35 N N I cl ci G CI Br N"b 1. 5662 N_Nf 2. 631. 35 N NEZ Br N1 / O 8r NiSo 1. 5663 N_Nt 2. 642. 35 N NAZI F F F F 1 F F Br N 0 1. 5664 N-N 2. 665. 37 N CX je-O B N' B N \ 1. 5665 NNt 2. 571. 31 N N TABLE 57 .. _ mlz Product 1. Ex. 2. product I. Ex. 2. m/z m/z Bu ber N N--- -N N-N 0,,/N 1. 5701 N 1. 5706 2. 535. 29 s N 2. 547. 3 o J o \ Br Br - B Br N-N r, N/ N N N 1. 5702 0 N 1. 5707 2. 540 : 3 2. 547. 3 o/\ o/\ I-IaC ZON Br Br Bu ber N-N 1. 5703 0 N 1. 5708 2. 543. 3 o s N 2. 554., 3 \ ! Br Br H, \ N bu ber N/I N/I /NN r--N N o 1. 5704 1. 5709 2. 543. 3 o S N 2. 555. 31 Br 5 _. 8r \N _\N Bu ex bu bu -N N-N (} 4 N 1. 5705 0/N 1. 5710 vs N 2. 547. 3 o S N 2. 555. 31 01, CH \N i w Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z Br Br i N N/I N-/N... N 0, s 1. 5711 0 N 1. 5716 ou 2. 559. 31 tSX X 2. 563. 31 zon '''1' CH, Br Br Br. _ __. _ _ __. _________. _ Br 1 N N O I /NN 1. 5712 p\ N- 9. 5717 , Su <N 2. 559. 31/, S N 2. 565. 31 F O--CH N F N Br ___-_-Br zon N N NN 1. 5713 p N 1. 5718 S9ew N 2. 561. 31 2. 565. 31 O i F O F F \N \fJ _. _ sr _. _ N N Br Br \ 1. 5714 0 N _- 1. 5719 N 2. 562. 31 N 2. 565. 31 '"''1"' cl--\----j N F F N N Br Br N--N--- //I N NN/NN ot r 1. 5715 ot r 1. 5720 N 2. 563. 31 N 2. 565. 31 \ N N CRI F Product 1. Ex, 2. Product 1 Ex 2. m/z m/z m/z /Z S N- N N __'3 \-, N-N (; WA 1 5721 ;} 4A 1. 5726 N 2. 569. 31 s 3 N 2. 581. 32 s/ cri N Cl N N ci B / N-c /NN H' 1. 5722 ii o 1. 5727 N 2. 571. 31 0 CH . N N H3C C Bu ber N S N__J (N-N __i , NN /N-N 1. 5723/N N-N 1. 5728 o N 2. 579. 32 tSko N 2. 587. 32 0 N N CH, go Br l/ N/ N-N N-N ob 1. 5724 N-1. 5729 N 2. 579. 32., s N 2. 589. 32 -~-u ce Nz Hic Hic N Bu B NN/N ! N F'NO vs 5725 OS N 1. 5730 ci o 2. 581. 32 0 2. 589. 32 / \N OC I N C.-O Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z Br Br N -v---- ;} N 1. 5731 0 N 1. 5736 2. 591. 33 o s N 2. 597. 33 H3C'Cl /\ , o ci foc oc N N- (' zu NON N 1. 5732 p\ S N -1. 5737 N 2. 597. 33 2. 597. 33 F F0 0 F CI N N Bu dz /nez N N 1. 5733 p\ -J -- 1. 5738 /1 2. 595. 33 o S \ N 2. 596. 33 ce ci bu ber F N/I //I /NON . y _/N 1 1. 5739 ° 2. 597. 33 bon 2. 597. 33 /\/won N Br Br N- (/ -N N-N 1. 5735 0 1. 5740 'S N 2. 597. 33 _ Cl tN 2. 581. 32 /\ N CN cri Product 1. Ex. 2. Product 1. Ex. 2. m/z Br Br 1 N y N-N F F zon + N-N 2. 605. 33 ° 2. 613. 34 bu N-N/N - C'a/ [. v °/Fo N- zon 0 1. 5742 -0-,/ 0 1. 5747 ° 2. 607. 33 con 2. 615. 34 /y Br Br 1 W-N N- N IN- 0-,/N 1. 5743 0 1. 5748 , s N 2. 607. 33 2. 621. 34 Bru ber Br Br Bu N N-N /nid 7 0,,/N 1. 5744 ON N ci 1. 5749 2. 607. 33 o S N 2. 631. 35 /\/v c \ v Br \N \N tJ f /N-N F N-Oy 1. 57454 oll 1. 5750 F 2. 613. 34 - v 2. 680. 37 0 , F F F TABLE 58 Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z ber s s a, a G N NN 1. 5801 1. 5806 2. 550. 3 pi 2. 598. 33 L CH, '=o fY. S 0 |-# w ouzo / _ _ Br N w Br N w Cl 1. 5802 N'N 10 5807 2. 590. 32 N 2. 602. 33 s 1'\/ Ng/1 NS w !/w 0 w O/QO F O u b Br N Br \G C ! /fJtJ e° 1. 5803 1. 5808 2. 598. 33 2. 602. 33 N N ' Ber a F sr \ s Cl N'rJ/ N, N 1. 5804 N 1. 5809 2. 598. 33 X o 2. 603. 33 zozo N HIC S/Sko CF6 //S 0--N/ Sur ber CA N 1. 5805 N_Nr 1. 5810 2. 598. 33 N 2. 609. 33 \ CHs /\ N . °. ° 0 0 O Product Product 1. Ex. 2. m/z m/z ber auf N. N, i Nw 1. 5811 N 1. 5816 f o 2. 609. 33 N 618. 34 zozo N-I' o ci - _-__ Br N- \NN 6 N-CI N 1. 5812 NIN N 1. 5817 2. 610. 34 2. 624. 34 N 0 N W S OS O / cl Cul Ne, Nf H3C 1. 5813 Ne, Nf 1. 1. 5818 818 2. 612. 34 CH, 2. 626. 34 N-N-0 I nu ps0 bar Cl G. Nz N N 1. 5814 N 1. 5819 , N 1. 5814 f 1. 5819 2. 614. 34 nit 2. 634. 35 s N -// Br N w 1 er dur Ber G N C-W3c\ 1. 5815 1. 5820 0 2. 614. 34 2. 632. 35 N-0 zip Product 1. m/z 2. 1. Ex. 2. Product m/z _.- bu ber N N a a N 1. 5821 NN 1. 5826 2. 636. 35 2. 648. 36 s its H'° \ a/ 0 bu \NN I N N 1. 5822 1. 5827 2. 640. 35 Cct 2. 654. 36 NS= N I Sep cet \ I \ I FfC CH N _ s 1 a NiN NiN f 1. 5823 1. 5828 2. 642. 35 2. 660. 36 o, Cbz N I- i O.. N 7/i cl B N w G N/CH 1. 524 ; 1. 5829 ó/0 ° CH3 rP =0 N, N H3Cs 1. 5825 A 1. 5830 2. 644. 35 2. 670. 37 iso 1 N, - oi° o c ° p at ber N o Ovo \ NnN, r a G 2. 644. 35 N-2. 676. 37 2. 644. 35 1. 5830 U°)- /\ o 1 w os. o 1 Py 9 Product 1. Ex. 2. m/z m/z 1 Br CL F N 1. 5831 2. 735. 4 1 o o Br ci G WN, NY 1. 5832 2. 522. 29 CH- N- sur Cl 1. 5833 2. 584. 32 N Nz /5 O TABLE 59 ow Product 1. Ex. 2. Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z m/z ci N N N iN/ \ N B a N N 1. 5901 1. 5906 1. 5911 2. 536. 29 2. 598. 33 X CC. 603. 33 N i N o=L ßNo . ___ 0 N 0-11 cl 0 Ct bit NiN d \tJ, N O \N'N/ N 1. 5902 1. 5907 1. 5912 2. 550. 3 A 2. 598. 33 vu 2. 609. 33 N N O / A N 0 18, N Br N\ v Br v B v if 0 CF \NN f N 1. 5903 fN 1. 5908 dN 1. 5913 9 2_ 590. 32 9 2. 602. 33 t 2. 609. 33 N N N o= Ì I 4 09 05 ---------f s vd N 0 0 , \ y N N N N 1. 5904 1. 5909 1. 5914 2. 598. 33 2. 602. 33 2. 610. 34 N o 0 F c __. _. /// ''' tN H ! v N a w N f a N N 1. 5905 1. 5910 1. 5915 N 2. 598. 33 2. 602. 33 2. 612. 34 0 O=S-o-p O=S O p_S \ S p I O 1 Fy ? 1 Ex 2 1Fy9) f Product 1. Ex. 2. Product 1. Ex. 2. Product Ex. 2. m/z m/z m/z il 1 il Br Br w Br w a ci N N a \ N J N N 1. 5916 1. 5921 N 1. 5926 2. 614. 34 b 2. 618. 34 q 2. 620. 34 o D n 5 o Yg w w ~ www- O-GIi F Bu ci NIN NN/\NN O \ N/ N 1. 5917 1. 5922 N 1. 5927 2. 614. 34 9 2. 620. 34 ton 2. 624. 34 N 0= S-P Br C, cul N, N Br \NiN CI \ A C7.. \/N CI N 1. 5918 N 1. 5923 dN 1. 5928 2. 616. 34 ton 2. 620. 34 2. 626. 34 F F N & H, c/0 F-O O --y _ /// Bu bu IN Nz NN 1. 5919 N 1. 5924 N 1. 5929 2. 618. 34 ton 2. 620. 34 t 2. 626. 34 NZ N 11-0= II F Gi °=119 i 0< Br v g v er cri C Br N A p N N N N 1. 5920 1. 5925 1. 5930 2. 618. 34 tNt. 620. 34 40 2. 632. 35 ZON gap0 N N o 1 a TABLE60 Product 1. Ex. 2. Product 1. Ex. 2. 1. Ex. 2. m/z m/z m/z sur N ci zizi zon 2. 536. 29 2. 588. 32 2. 595. 33 0 N q 'ILS ........ B B 1,,...... _... _...... Br Br Br C'cri N N CA 6002 1. 6007 1. 6012 2. 576. 32 2. 588. 32 2. 595. 33 OC N Ov N p N 5'5 p'' O ,, S 0 F n \\N _-/_.. ___ _ N - _--_ CI a a NN B NN N-N N N N 1. 6003 1. 6008 1. 6013 2. 584. 32 2. 588. 32. 596. 33 F w tA 4 <4 vs , 5 a ci N- nul N Q q B _ N-N 1. 6004 1. 6009 j 1. 6014 2. 584. 32 2. 589. 32 2. 598. 33 N S O N OS N S Cbz O o ou . _ ----- Cs m _ ( N , 5M NsN rS'y p 5 ns N_ _O N o O NCH C6 CHI Product 1. Ex. 2. Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z m/z r a r i 1 _ i/I r s IN-N 1. 6016 1. 6021 1. 6026 1. 6016 1. 6021, 1. 6026 2. 600. 33 2. 606. 33 2. 612. 34 0 N s N 5t 5 cet F Br 8, N/--N S I N / N-N N-N N 1. 6017 1. 6022 1. 6027 2. 602. 33 2. 606. 33 2. 620. 34 0 0 \- O F O F W W . _-_/ bu cri ill 1. 6018 1. 6023 1. 6028 ts XN e 2. 604. 33 2. 606. 33 2. 620. 34 N-q_o L N p N S/ O . O v C et eA a NN I/ N-N I -N N N r r 1. 6019 1. 6024 A 1. 6029 2. 604. 33 2. 606. 33 OXS r 2. 622. 34 a F F o', SaqF 0 On Q On F On F /N-IN N N N 1. 6020 \ 1. 6025 v 1. 6030 2. 604. 33 2. 606. 33 2. 626. 34 N O a ci en, F Product 1. Ex. 2. Product 1. Ex. 2. Product 1. Ex. 2. CA C eA a G N_N / N-N \//N N __- N N 1. 6031 1. 6036 N 1. 6041 0 2. 628. 35 2. 638. 35 2. 648. 36 No, at NI X'ó U U° 1 J F 'O N CA 1 e. cri N N N N 1. 6032 i 1. 6037, 1. 60425 2. 630. 35 2. 630. 35 2. 638. 35 N // Xb e O S CFS I F 1 _O FiC F g fizzy r.... _..., . . ° ..... ___ e a a er I-N N N N-N N N 1. 6033 1. 6038 1. 6043 2. 630. 35 2. 638. 35 : :- s- O-cil s cH, o/ o ° e _ ____. _ N N ___.- a 1. 6034 1. 6039 1. 6044 2. 634. 35 2. 622. 34 2. 648. 36 N of ta OJS O S , % C-O B, C, N ver N-.. i/' G N N N N / N-N H 1. 6040 1. 6045 N 2. 646. 36 N o. 654. 36 eN ó-' " : O F F F4-1 F'-F F Product 1. Ex. 2. mlz p. ... N /.....-__-. O S N-N N 1. 6047 2. 654. 36 e F. o FJ F a -A CA 1. 6048 9. 6047 2. 662. 36 ao N- Ut e zur N 1. 6048 2. 662. 36 0 a 1. 6049 ft : a N-l'o 2. 721. 4 F F RIF F-,, F v N N 1. 6050 2. 570. 31 OJ N osez TABLE 61

1 Py 9 1 Pv O Product 1. Ex. 2. Product 1. Ex. 2. mlz m/z Sr Br bar N a iN/G \ N S gN 1. 6101 No N 1. 6106 2. 584. 32 2. 588. 32 N, Nz O=R lol Br B Br N er N G CI \NN/\ N d N gN 1. 6102 fN 1. 6107 2. 584. 32 2. 595. 33 1 OH3 N chu -, 4L ber 13 Br N Br N Cl NN/ N 1. 6103 N 1. 6108 2. 584. 32 XN 2. 600. 33 1 1 N w N 11 O O \/C o O er N er G CA Br Ne, NÓ Br N, SN g N N 1. 6104 N 1. 6109 2. 588. 32 2. 602. 33 1 F -N Our F FlC /1 Br 1'r Cl NiN/\ iN/ , N N 1. 6105 N 1. 6110 2. 588. 32 N 2. 604. 33 \1 zon F CA F a Product 1. Ex. 2. Product 1. Ex. 2. _--_, -_ i i 1 Br"r C3 Non N 1. 6111 N 1. 6116 2. 604. 33 2. 606. 33 0=5 O=S F N cl F Br N w 1 N \ 1. CI CI v N w N/ 1. 6112 N 1. 6117 2. 604. 33 2. 606. 33 razz i F F N N N N NN \ N 1. 6113 1. 6118 2. 606. 33 N 2. 648. 36 0=0-P-F 0 F bu F bu Br bk ,, N N N Br n1 er N, N s 1. 6114 1. 6119 2. 606. 33 SNe 2. 721. 4 6-N, F O=R 0 F o 7b zu Br N\ B Ber NN \ N N 1. 6115 1. 6120 2. 606. 33 2. 570. 31 0 fun 0 O=R O-II/ w N- O F

TABLE62 Product 1. Ex. 2. Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z m/z - __ _ riz ar v \ N CI N''N/G \ N O G N 1. 6201 fN 1. 6206 fN 1. 6211 2. 514. 28 2. 576. 32 2. 581. 32 6N t3 N N N ci N < ° (Q" N N N N 1. 6202 N 1. 6207 1. 6212 2. 528. 29 2. 576. 32 2. 587. 32 N 1 \ O N N I e. arN\ 'er Y \ N/G \ N G iN/ N N N N 1. 6203 N 1. 6208 N 1. 6213 2. 568. 31 2. 580. 32 web. 587. 32 N 1 1 g S-O g O \N . _-- N Br\ N\ Br \ Br N a G N/N N J N N (N 1. 6204 dN 1. 6209 (N 1. 6214 g2D 2. 576. 32 gS 2. 580. 32 2. 587. 32 N NJ °=11 ßn NX 0 F N 70- 13 B NdoNS NdoNS BreN, \Ngf Nez dN 1. 6205 N 1. 6210 gN 1. 6215 2. 576. 32 2. 580. 32 2. 588. 32 N \ p W J N lol --------- m/z m/z rn/z 1 1 Br E3 rA N N 1. 6216 gN 1. 6221 gN 1. 6226 2. 590. 32 gel 2. 596. 33 g2f 2. 598. 33 N N N I CH, F a F 0 cl F 1 ci N N/a a v N A N N 1. 6217 N 1. 6222 N 1. 6227 2. 592. 33 2. 596. 33 2. 596. 33 N F 1g N G O Fir B B a IN N 1/ r N w 1 Br N\ w 1 Br N w v NN/G S a \ N J N N 1. 6218 N 1. 6223 N 1. 6228 2. 592. 33 2. 598. 33 . 2. 602. 33 () \ tN O N O' p F O S 11--% 11s 0 0 s cl Ber N N 1. 6219 N 1. 6224 N 1 6229 2. 592. 33 b F 2. 596. 33 2. 604. 33 o=S NW NV S F F N N Pics C O- 0 in- __ Br w Br w 1 Br w ion N N A NN dN 1. 6220 gN 1. 6225 N 1. 6230 2. 594. 33 2. 598. 33 2. 604. 33 F - , Oil/ O F CH I m/z I c 1. Ex 2. Product WXTx 2- m/z r mu m/z M/z m/z --q ni Sur N_- 1. 6231 1. 6236 N 1. 6241 2. 610. 34 2. 614. 34 t) 2. 630. 35 N (1 1) X o N \ SGO 0 0= p=S-P N o \\ CI vC'F F C" Br N fir Br v ci e a N 1. 6232 N 1. 6237 2. 610. 34 2. 618. 34 2. J 6 N, C, o i O=s N, F 0 F a Ci-6 G G NN J CI \N ! N N 1. 6233 N 1. 6238 N 1. 6243 2. 612. 34 ( 2. 622. 34 2. 630. 35 N N F I 0 Ors . r, y T 0'cl Br 6 w B N\ ar Cl ci N 1. 6234 N 1. 6239 gon 1. 6244 2. 612. 34 O 2. 622. 34 2. 630. 35 N 6N 0ICF ors P, 0 0 0 Ber Viz N N NN I N N \N J 1. 6235 1. 6240 N 1. 6245 2. 614. 34 Xs 2 626 34 4 630 35 N 1 ruz o Di X,} D -0-- a n, c a 0 1 0 Product 1. Ex. 2. Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z m/z N__ r Cl cri -nu NN J G ZON N 1. 6246 N 1. 6251 1. 6256 W 2. 630. 35 A wa 2. 636. 35 N 2. 646. 36 a a ou N G I o ci ci Sur CI CI F CA Br w B N Br N w G /CI N. N CI ton 1. 6247 N 1. 0 6252 N 1. 6257 2. 630. 35 2. 638. 35 2. 646. 36 °=151< N -0 F F O F /i i I Br w Br N er N B rA N 1. 6248 N 1. 6253 su 1. 6258 t 2. 630. 35 X 2. 640. 35 N 2. 648. 36 zozo 6 N lO Nez ber i - Cl cri N \ N/G \ N/CI \ N/G N N N N 1. 6249 N 1. 6254 1. 6259 CA 2. 630. 35 2. 640. 35 6N 2. 654. 36 N CA Sr Br p cul N N \NiN N 1. 6250. N 1. 6255 k 1. 6260 6N 2. 632. 35 2. 638. 35 2. 713. 39 ro N 0 er F O-O Br oF Product 1. Ex. 2. m/z « r Br Nd, Nn Cl ci N N 1. 6261 6N 2. 500. 27 1 1 0 O 0 Br N N N S N N 1. 6262 2. 562. 31 o=liç s N N 1. 6263 2. 604. 33 c LU o= \ ! foc TABLE 63 Product 1. Ex. 2. Product 1. Ex. 2. 1. Ex. 2. m/z Product m/z I G I G G B'Br Br N 1. 6301 1. 6306 1. 6311 H-N N 1. 6301 1. 6306 1. 6311 Hnd 500. 27"-N 2. 562. 31 \- 2. 567. 31 foc / g ° o-v, o o o /\ G/\ , oi > X ou Br-B N Br r, 5 1. 6302 1. 6307 H N 1. 6312 H-N N 2. 514. 28"-N N 2. 562. 31 2. 573. 32 CF6 S" '<--- \-///i ° ozon ci ci CI - _, Br Br Nl F \ B- er nu 1. 6303 N_ H-N 1. 6313 2. 554. 3 2. 566. 31 2. 573. 32 oi 0 v I, o o0 1_ o, F N ber Ber sr g, 'Bf 1. 6304 1. 6314 1. 6314 2. 562. 31 H N 2. 566. 31 2. 573. 32 0 t 8, o o A O F G llr Br Br Bu gNW 1. 6305. N 1. 6310 1. 6315 2. 562. 31"-N 2. 566. 31"- 2. 574. 32 zu po oHc o o \ \/. 0 1. Ex. 2. 1. Ex. 2. Product mlz /\ 1. 6321 Br N NU 1. 6316 ex 1. 6316 N 1. 6321 N 1. 6326 2. 576. 32 H-N 2. 582. 32"-N 2. 584. 32 c s S 5 5 p G O \\ O F cl G Br Br Br Bu 1. 6317 22 1. 6327 H-N N N 2. 578. 32"-2. 582. 32 H-N N 2. 584. 32 H-b H-N N/G i S g ! O.. CFia i O \O O O F G Br-Br ex 1. 6318 N. N 1. 6323 N 1. 6328 H-N H- 2. 578. 32 2. 584. 32 2. 588.-0-4' D., °'\òV F 5-w w-L 0 F 0 'S -.-,. I G I ce sr Br > J t3CI 1. 6319 1. 6324 tNW 1. 6329 Nazi F 2. 580. 32 2. 582. 32 HN N 2. 590. 32 2. 590. 32 \ CHa O N l 0 oi. \\, o . __ cul a llr gaz Sur N nu 1. 6320 1. 6325H N 1. 6330 N 2. 582. 32 N 2. 584. 32 N 2. 596. 33 F s \ s CA F F G Product 1. Ex. 2. Product 1. Ex. 2. 1. Ex. 2. Product m/z cri /\ G/\ - N 8 gr Br rv WaN 6331"w"1. 6336 H N 1. 6341 rN 2. 598. 33 2. 606. 331 f o 2. 616. 34 o s v °o i--- F S\ CA ci _N-\ Zur ber 1. 6332 H N N uo, 25\. S 2. 608. 33 2. 616. 34 s ouzo 0 ouzo a I er-"N Br Br 1. 6333 1. 6338 1. 6343 N r4, 0 0i \\ 'p SOCI O G CI ci5 \--P/, 0 0 1. 6334 1. 6339 N 2. 600. 33 2. 612. 34 616. 34 N-CF 0 ou axa CF ci cri N Elr ber Cl er 1. 6335 g 1. 6340 S 1. 6346 L N, o 2. 604. 33 L s v_ o lu, o \I F o-\\ F F O G -.. 1. Ex. 2.-.. 1. Ex. 2. 1. Ex. 2 Product 1. Ex. 2. Product 1. Ex. 2. 1. Ex. 2. Product m/z r4 aza G/\ a Hr-er g f Nd 1. 6346 t8Br 1. 6351 0WBr 1. 6356 2. 616. 34 HNbN 2. 622. 34 HN N 2. 626. 34 G G I bar \-\ a a b O-S s ¢Ta (O) e Ea 0C$ l a 0 Ber -N Br Bf 1. 6347 H N 1. 6352 1. 6357 Nx a 2. 616. 34 ad o 2. 624. 34 X o 2. 632. 35 , o S' cl $ I F O G ci Br ni 1. 6348 H ta 1. 6353 H-t4 1. 6358 H-N 2. 616. 34 2. 626. 34 su 2. 632. 35 NS*O o cl, Zozo O S /C \ os ¢9 Fg X CA a a a tb Br t Br H£d3 "-N 1. 6349""1. 6354 1. 6359 2. 618. 34 2. 626. 34 10 2. 634. 35 ° HCs X ct H, C CC óhO C o S, osoo c. o I G G/ e Ea a ber 1. 6350 1. 6355 h f W 1. 6360 Nv 2. 600. 33 2. 640. 35 a 0 0 po o' o F Br 1 Py7 1 Fx ? Product 1. mlz 2. Product 1. m/z 2. m/z m/z - a "-N 1. 6361 N 1. 6366 2. 650. 36 N 2. 486. 27 °/\ S, l N CH3 Zozo F F /\ G/\ Br Br er \ N NJ 1. 6362 XNWBr 1. 6367 2. 650. 36"-N 2. 548. 3 c s v cl 0 0 cri a Br 1. 6363 ber 1. 6368 H-N N 2. 661. 36 2. 590. 32 C _NX CF bon six O B htjC Cl cri 1. 6364 H-NJ F F F 2. 684. 38 *--S 0 F F cl zur H-N 1. 6365 2. 699. 38 'N F F 0 N F TABLE 64 Product 1. Ex. 2. Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z m/z s zig / I, N r N-N i N N J 1. 6401 1. 6406 2. 474. 26 1. 6411 f 1. 6401 f 1. 6406 N 1 6411 d 474. 26 2. 536. 29 2. 541. 3 N,/ ? °. ° 0 c C Fc ! HjCX ci Br ci ci __ a r N N i /f l N-N N NN 1. 6402 N 1. 6407 1. 6412 Os, S 2. 488. 27 N-Is 2. 547. 3 0 o s' S C H3C cul N CI N cl Br N N N N XNN f 6X 1. 6403 1. 1. 6408 (1. 6413 2. 528. 29 2. 540. 3 v 2-547 3 O N Oo N s s ou zu au _ _.- /i ///\\ ( ( 'N/I I/N r \-N-N \ Nz 1. 6404 1. 6409 1 1. 6414 N\ 0 2. 536. 29 a N 2. 540. 3 1," t ofsX go o "s F \ I ci cl' I \ G q r N-N YN-N N N 1. 6405 1. 6410 2. 536. 29 N ; ; 2. 540. 3 2. 550. 3 N O. as' --S C F 1. Ex. 2. Y 1. Ex. 2. 1. Ex. 2. Product, Product, Product'-'='""- m/z m/z m/z cri /N/ I/N r I (N-N/N-N \ NN 1. 6416 N 1. 6421 zon 1. 6426 o, 2. 552. 3 | Ns ; 2 556. 31 2. 558. 31 g'N., O N 'S cl Br Nz N a e Bf a N N N , N 1. 6417 F \ NrN 1. 6122 1. 6427 2. 552. 3 N 2. 558. 31 o sN 2. 564. 31 o, N i N. o a H bu bu C C I N i bu ber 'N 1. 6418 F 1. 6423 N 1. 6428 N 2. 554. 3 N 2. 558. 31 2. 572. 31 tH3 ° X ó/0 X w < (N wN ( ("T ci B ci I a \. N N u N-N NN N 1. 6419 f 1. 6424 Nx 1. 6429 2. 556. 31/2. 558. 31 N,, p 2. 572. 31 O. N O ao cz°t at b CI- ci pu N N-N N N-N 1. 6420 F N-N 1. 6425 1 1. 6430 f 2. 556. 31 11 Q N 2. 558. 31 2. 574. 32 o s N F V \ iNW/'co FCl- 00/s 0/--o a Product 1. Ex. 2. Product 1. Ex. 2. Product 11. Ex 2. m/z m/z m/z Br Br C'c'I- N /N N NrN" /N- N 1. 6431 f 1. 6436 Cl 1. 6441 CH, N 2. 574. 32 2. 586. 32 N 2. 590. 32 NC-N N, s cl cl 0 ci 0 _..,. wN N'N r d cri _nu "-N N N-N \ N. N \ N N s J N 1. 6432 1. 6437 ci 1. 6442 2. 578. 32 % O 2. 590. 32 A N 2. 590. 32 N / Se0 F N F 1s0 F/) ', o a a q sr r N _ N -u L wN XN eA L Na 1. 6433 1. 6438 1. 6443 2. 580. 32 N,, p 2. 590. 32 2. 590. 32 t4, 1/0 0 IN ( g oll, a CH i . a B w °'Br 1 I % CI N-N NN N I I Ayg N t (1. 6434 X 1. 6439 G, 1. 6444 2. 582. 32 N, 2. 590. 32 N 2. 590. 32 CC N zu Du 119 ou 0 FIJC CkIJ F Fc \---i a ar ci _ N -- N 1. 6435 (1. 6440 Cl 1. 6445 2. 582. 32 2. 589. 32 N 2. 590. 32 =0 N L 10 col H, c° a O Product 1. Ex. 2. Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z rn/z ci ci f i r zu N \ 1. 6446 N 1. 6451 1. 6456 1. 6456 2. 592. 33 2. 600. 33 ° 2. 614. 34 '°, o Chez v% bu i cri cr, g o M a5 \/ W a G Br I N I/N \ N N 1. 6447 1. 6452 N 1. 6447 N 2. 574. 32 2. 600. 33 0+5\\0 2. 673. 37 N, PI F N ( : Ber 0 0 In 10 cl ber N N o sa Br N N-N N k 1. 6448 k 1. 6453 N 1. 6458 0 2. 598. 33 d0 2. 606. 33 S 2. 460. 25 .---0 0IN F/ S F Cbz sil 1 CI Br r i N N/ 1_v y "1. 6449 1. 6454 2. 600. 33 N,, ° 2. 606. 33 6459 2. S C, sN i N//\ Oo aN tri O O o O z C4 \ G I y a pr y ce 'dz _,. \ NH N N mg 6460 --o 1. 6450 , 0 1. 6455 1. 6460 NsSP 2 60033 d 2. 608. 33 Hc CH3 N 2. 564. 31 SIZ. o i, o O H 3

TABLE 65 Product 1. Ex. 2. Product 1. Ex. 2. product l-Ex. 2. mlz ..... __ ci r N-N N-N nu N-N N 1. 6501 N 1. 6506 (1. 651 1 -0 2. 488. 27 L 2. 550. 3 S-10 2. 561. 31 r',,'o so o_, er q a zon a CA ci / N NON tA Sr wN 1 f 1. 6502 Nn 1. 6507 X 1. 6512 2. 502. 28 2. 554. 3 2. 561. 31 No 0 Xr N ¢<r ci C'ci F _N _N_T y cy_ _w a r r w i N h i _ \ NN d \ NN Nn 1. 6503) 1. 6508 Nn 1. 6213 2. 542. 3 2. 554. 3 k 2. 561. 31 N N S--Os/ O p /\ . \ G ... -Cl a / \ NN \ N N-N N) 1. 6504 N 1. 6509 1. 6514 2. 550. 3 2. 554. 3 N) 2. 562. 31 N N s Xr Sr 9f r Ors In Y" yv JL/ ci I \ \ G \ G N /N I N I f i T i _/i A \ NN \ NN \ NN 1. 6505 N) 1. 6510 Nn 1. 6515 2. 550. 3 2. 555. 31 2. 564. 31 I \N 0 I'S O I s N o P o is

Product 1. Ex. 2. Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z m/z cl cri r r N 9d N r N-N N- 1. 6516N 1. 6521 N 1. 6526 2. 566. 31 X 2. 570. 31 2. 576. 32 N ci r N N a N-N j N-NI N N 1. 6517 1. 6522 Na 1. 6527 N ! 2. 566. 31 o=r 2. 572. 31 l 2. 578. 32 N N N i O/5 O 9 e 1 CHa O iW : O 1 A F e o F CH I N-N ¢k$r is eS ! 1. 6518", I 1. 6523 1. 6528 N F 2. 568. 31 XN F 2. 572. 31 2. 586. 32 N F N F 1 o ~ m n---ß-- p ll HC I \ I \ Q a e r is Nz \ \ N) 1. 6519 Na 1. 6524 f 1. 6529 2. 570. 31 2. 572. 31 2. 586. 32 N-N N In O F I/ ---=s 9Sr 9gN e a a r r i N N 4 1. 6520 N) 1. 6525 f 1. 6530 o, N 2. 570. 31 N 2. 572. 31 N 2. 588. 32 F \ O Oos 1 O=g 1 v 1 Sv O 1 O O 1 a pua 4 Product 1. Ex. 2. Product 1. Ex. 2. Product 1. m/z m/z m/z - N 1 N N d \ N \ NN N \ NN 1. 6531 1. 6536 1. 6541 2. 588. 32 N 2. 600. 33 2. 604. 33 I v > 0-S - O a Cbz lc ci c, cl ber a N N N N 1. 6532 1. 6537 N 1. 6542 2. 592. 33 2. 604. 33 \N 2. 604. 33 zon 5 \ O s EC aH, F F a O 1 G F G "---y . ___ N I f f G Gl _ N N S _ N N N N NN 1. 6533 1. 6538 N 1. 6543 2. 594. 33 2. 604. 33 2. 604. 33 80 SGO N i oo i ao a I o=S a ci B, OWN N N __.-G _. B-_. _.. _- a N \ S = N N N-N \ N N N N N 1. 6534 s 1. 6539 f 1. 6544 tN 2. 596. 33 1 2. 604. 33 2. 606. 33 o, ---w 0 1 0 g F I r c F F FiC CI-f a I/N_/Nr I/N r i i f e \ NN \ NN \ 1. 6535 N 1. 6540 Na I. 6545 2. 596. 33 N 2. 604. 33 2. 588. 32 O=s-I \ N 0 1 p o ° S 1 o= 0/ils o / a F 1 fY 9 1 Fy 9 *< c\/o Produ 1. Ex. 2. Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z m/z a B, ci Br /N-N , j Nez 1. 6546 V 1. 6551 gN 1. 6556 1. 6556 2. 612. 34 2. 620. 34 . 34 2. 474. 26 i w s s ,. U Fuzz w F o \ O N-- N N ion /N--N /_ N.-N i \ non 1. 6547 1. 6552 N 1. 6557 2. 614. 34 2. 620. 34 2. 536. 29 N O \ i0 S'S N CH3 O=Z 0 a °o o 0 1 e ci ....... _ CI _No /N-N 1-N_rv/i r N 1. 6553"N 1. 6558 2. 614. 34 n, o 2. 622. 34 2. 578. 32 5 ; S' ors °s I ° o ouzo a ci Br r r « y ? N-N \ Nz N 1. 6549 1. 6554 2. 614. 34 2. 628. 35 N ° so r Cc oer 1 f I o N nu _N N YNN Nn 1. 6550 X 1. 6555 2. 614. 34 N 2. 687. 38 ors Zu l-D Br 04F F TABLE 67

-Product 1. Ex. 2. Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z m/z ci er a ci w N I \ Br r C_N El N-N N-N N nul_ N 1. 6701 N 1. 6706 non 1. 6711 N N 2. 474. 26 1 2. 526. 29 2. 536. 29 N N O ! 0/Cbz f \ G \ razz /j1 N i N i N I \ NN I \ NN) N non 1. 6702 N 1. 6707 N 1. 6712 2. 514. 28 N 2. 526. 29 N 2. 538. 3 2. 538. 3 N w 11N r r cir N N I'N N r Nz i j.. N C N-N N i N 1. 6703 N 1. 6708 N 1. 6713 N N O=S w N N ! I O=g w Oc w 0'N N IN ___ r \ NN \ N N \ Nv CON N 1. 6704 N 1. 6709 N 1. 6714 2. 522. 29 NI 2. 533. 29 O IS 1 w 0% S 1 w N F O O N 0= CI \ CI g \ G t o : : : F i N , ils 0 0 N-N N N-N/ N. 6705 1. 6710 N 1. 6715 522. 29 N 2. 534. 29 2. 542. 3 zozo N S N Og w \ O ; g w O a 1 Ex 2 1 Ex 2 1 Ex7 Product 1. Ex. 2. Product 1. Ex. 2. Product | 1. Ex. 2. m/z m/z m/z a r r /, t / IN \ \ i w N 1. 6716 N i 1. 6721 g 1. 6726 2. 542. 3 2. 550. 3 2. 564. 31 N Po L CH,) C cn, O \ 1 C i C I/O G C'a C C'a ayez 07 0 1, G r r /N / / 1 YI/ N-N N-N N N 1. 6717 1. 6722 1. 6727 XN | 2. 542. 3 N\ 2. 558. 31 2. 566. 31 , N S\ o o_ ° °o - s U U Y ( 9 \ G w r e r i v N_N B N non 9Xr a ¢<r N, 1. 6718 1. 6723 i1. 6728 2. 544. 3 N 2. 558. 31 N 2. 568. 31 i N, s, o ___ t _. _ _ s F I F CNs i -.--... _-.. __ HCI a cl Nr N i I _ nez \ non N 1. 6719 N 1. 6724 N 1. 6729 1, 2. 544. 3 L 2. 560. 31 N 2. 568. 31 0 O=zp c o=s o=s n c, 0 1 0 0-F F a r HCI r /N/N i i i i i _ | m \ NN \ NN N 1. 6720 N 1. 6725 N 1. 6730 xi 2. 544. 3 2. 560. 31 IN 2. 572. 31 I 0 g w o v 0 G C c F CF 1. Ex. 2. 1. Ex. 2. 1. Ex. 2. Product 1. Ex. 2. Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z m/z , r I N r a 13r cl \ NN \ NN f 1. 6731 N 1. 6736 N 1. 6741 1. 6741 N 2. 576. 32 t 2. 576. 32 2. 586. 32 0 N N 07 O % 5 O=S w O ou= 1 F F a Br I \ CI.... ____ \ CI cl ci N \ N d in 1. 6732 N 1. 6737 Nu 1. 6742 2. 576. 32 2. 576. 32 2. 586. 32 , o So o=S C N F O /O S I \ Zur ~ Br A Q aX Nz w w NU 6 6 _ N_N _ N_N N N N 1. 6733 N 1. 6738 1. 6743 N 2. 576. 32 N 2. 576. 32 N 2. 592. 33 ry rY F) 0 Mf-X ° F T W__ __ w _ F F Fc C-H3 r ci bu w r N / 1 / \ non \ w N-N N 1. 6734 (N 1. 6739 N 1. 6744 2. 576. 32 to 2. 584. 32 2. 592. 33 0 N I s\ N'o O o f \ \ o F//I SO \ ci F 0 CA Br Br N Nr IN NN-N \ N_'N \ N_N i \ NN I N 1. 6735 1. 6740 N 1. 6745 2. 576. 32 N 2. 586. 32 X 12-600. 33 N N SO N s 1 ° Sso i Ó va 0 i

TABLE 68 Produit 1. Ex. 2. produit 1. Ex. 2. m/z m/z I N N r G N 1. 6801 N 1. 6806 N 2. 488. 27 2. 550. 3 c l N'H'N-5 Nl N +=NN bu ber f i N N-N i r a 1. 6802 N 1. 6807 j '2. 502. 28 ' _o 0 2. 554. 3 " CF cl,, w 0,. 0 O F o, ll/ N, s b-l=o c l-, _ _~. f N243 C j N 1. 6803 a 1. 6808 xi 2. 542. 3 NH 2. 554. 3 N I N N Bu ber I . ci 1. 6804/N N 1. 6809 2. 550. 3 2. 554. 3 N-CF N-CF6 0 C O I F Cf N "T"° °Y 13r 1. 68058 1. 6810 2. 2. 3"'Ne 2. 555. 31 r IN L. _ 3 Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z Br ce NN- I N Br o N ci 1. 6811 eNN N 1. 6816 2. 561. 31 2. 566. 31 N'CH3 ao, C, CiN l Eir Br ex ex N-N N G 1. 6812 1. 6817 =o 2. 561. 31 N 2. 568. 31 cFb Nrf _ m I IN F \ Na NS ber Nit N Ion N N Br 1. 6813 BreNoN N 1. 6818 H3C'N ci 2. 562. 31 S 2. 570. 31 <° ; ki o-, NS ; a O O cri cri N N 'cl N 1. 6814 B 1. 6819 N-C'6 2. 564. 31 N1CF6 2. 570. 31 0 o-9 ci Ber ot o=ssX O CI Bu CI HC N / er Cl 1. 6815 N 1. 6820 2. 566. 31 N l 2. 570. 31 Nz 0. ou CI Product 1. Ex. Product 1. Ex. 2. m/z m/z o-//s a N -N N Br N 1. I 1. 6826 ci 2. 571. 31 2. 576. 32 ceci O F E I \ ils ce F G, 1. 6822 _N 1. 6827 2. 572. 31 2. 578. 32 N nazi Cbz o i I c w , N O S=O CI N FC'NN Nx N CF /=NX 1. 6822 N>N lN 1. 6828 2. 572. 31 6 s CH, 2. 586. 32 N w __ O .. ... _-. _ F OS O Nv I OS w w N C--N \N I'ls Fuzz 1. 6824 ci 1. 6829 2. 572. 31 N 2. 586. 32 Ntr N N Br 0 Q S=p ci N N er 1. 6825 Br@N 1. 6830 N 2. 572. 31 2. 588. 32 f Ni H' O=S v cl G Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z N/ \ o , N-N c_N G 1. 6831 NA 1. 6836 2. 600. 33 / c N_yo 0 N N 2. 588. 32 N-P, Ber XN ; i I i G NN 1. 6832 1. 6837 \, 2. 592. 33 2. 602. 33 , ca' F via H, C F /IS CH in ci N N 'N 1. 6833 CF 1. 6838 2. 614. 34 0_5 2. 604. 33 0--S N 11 N Br F Br bu N non NN/CI i 1. 6834 1. 6839 2. 596. 33 2. 604. 33 N NiCHa S CH,/F F F N N ber N ag i 1. 6835 B N'CH, 2. 596. 33 N CF 2. 604. 33 r . ors 0 in- O p e, C G G Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z Br 0 -)/ a CF6 N-N G f N_N i I G C 1. 6841 Nz N 1. 6846 foc 2. 604. 33 Y 2. 606. 33 cl N ci G Br d I N 1. 6842 BrelN N 1. 6847 2. 604. 33 N 2. 588. 32 N-Cbz ° ; s o=s _ XNN _ _ CX G i Ber N ci N-N Cul N N 1. 6843 N 1. 6848 2. 605. 33 N ber 2. 610. 34 =o Lazzi cl so cl Cl Q 6849 . CI N1 d N N N 1. 6849 N N N 604. 33 0 0 / 2. 612. 34 N °=8l90 cl Ci I Ber Br/N', Bf N, N 1. 6850 2. 604. 33 0 I-LC Oa _N cl, ci a 1 Py 9 1 Fy7 Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z ber 0 s /" - 1. 6851 N a 1. 6856 N Br 2. 614. 34 0 2. 620. 34 H, C- 0 o\\ o B r cul N C Ni O7 /C N IN 1. 6856 1. 6856 N/N-CH3 2. 614. 34 2. 628. 35 2. 614. 34 N' /) c ci N N El 1 i CI N \ N I N SWN 11 F I I/N O O O N'N 1. 6853 B 1. 6857 N, 2. 614. 34 2. 687. 38 Nct S \ o ber cri N N a \ C _ N 1. 6854 (\ vBr 1. 6859 0 2. 620. 34 N 2. 474. 26 s% N F 2. 620. CH3 ___. F '\, o/\ F H3c CH, N bu ce 1. 6855 N 1. 6860 oussCc 2. 620. 34/No 3 2. 536. 29 I'N a Oc off F O F TABLE 69 Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z cl Br CA Br \ N_N \ N_. N C NX 1. 6901 N 1. 6906 2. 514. 28 2. 580. 32 6N/-CH :, S O OS F CI g, G Br N N w N-N N. _ 1. 6902 1. 6907 2. 568. 31 N_sg3 2. 580. 32 d ó/0 N ci Br Br bu 3 /I N-N N-N N 1. 6903 N 1. 6908 2. 576. 32 F 2. 580. 32 U TO -S 0 CH,"0 0 00 0 ou Br Br a Br 1 N-N NIN 1. 6904 N 1 6909 ton 2. 576. 32 0 c 2. 581. 32 c CH3 O N\ I, N c,, r CA Br O N-N N-N Br G Br 1 w N-N N 1. 6905 1. 6910 L 576. 32 2. 587. 32 \ N i, N N p SO OS\ 1 F7 1 Fx7 Product 1. Ex. 2. Product Ex. 2. a sr q Br a Sr aBr X at N-N N 1. 6911 N 1. 6916 0 2. 587. 32 F 2. 594. 33 6 0 _ _ _ ~ N t < N 1. 6912 N 1. 6917 t ci _. :, ci Br Br N N N-N N-N 1. 6912 1. 6917 2. 588. 32 tN sX 2. 596. 33 N-N \ _ __ __. a Br cl Br N N N-N N-N c c N 1. 6914 N 1. 6918 2. 590. 32 2. 596. 33 6N 6N //-, o-0//S . C) sr 0 Br N N . ... _.., _... . _. CI Br a Br /N-N N-N 1. 6914 N 1. 6919 cl, 2. 592. 33 cl 2. 596. 33 3 0 ou/00 ci bar %///%// _ N-N 1. 6915 N 1. 6920 N O tX Q 12. 592. 33 F 2. 598. 33 æO I t"S N l I O l F o ° l l _ _ I. I 10 Product 1. Ex. 2. Product 1. Ex. 2. , tn _ a Br m/z m/z .. bar a Br a Br N 1. 6921' 2. 598. 33 6N 2. 604. 33 j \/ NSw zozo p p O O Bu roi-N NIN N 1. 6922 (1. 6927 2. 598. 33 0 2. 612. 34 F \/,, S N OS O. F .. CI Br cl Br N At N w N F 1. 6923 /\ 1. 6928 N 6N F 2. 598. 33 0\ ß 2. 612. 34 F N N S\p O/SO t CI Br a Br wa Br wa Br N N Nez N F 1. 6924 N F 1. 6929 2. 598. 33 xi 2. 614. 34 F G 6N F 6N--a 0F° Ó/SiO a Br a Br /CI il \/i il N-N-N N 1. 6925 N 1. 6930 2. 602. 33 2. 614. 34 N C 0 C'0 iN S ci 0/"o CI O Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z G r G f 1 N /N-N NZ N-N 1. 6931 1. 6936 2. 618. 34 2. 630. 35 NS so 1 F oc 0 0 cl CA --N N N 1. 6932 1. 6937 2. 620. 34 \N t=O 2. 630. 35 o-CH, F NS= O pCH, /F F C Br a er N 1 s N / s i v N_N N-N 3 /cl, 1. 6933 1. 6938 6N 0-2. 622. 34 N_llO. 630. 35 s=o - xi N//. S\ O O_CH3 F F | Br a Br N N 1. 6934 N 1. 6939 2. 622. 34 tN~s. 630. 35 ~ _. 6N CH, 6N L 1 nez Br a Br N Nz N-N N-N 1. 6935 N 1. 6940 2. 626. 34 2. 630. 35 s Oo , I-0 1 Ex 7 1 Fx9 Product 1. Ex 2. Product 1. Ex 2. m/z m/z .... S_ f w /N-N N-N N 1. 6941 N 1. 6946 2. 630. 35 2. 636. 35 cl N S N O5 O G CI O SO c 0", S"lo f Ber ber zon N ci 9. 6942 0 1. 6947 2. 630. 35 2. 638. 35 | Iw ber er c e' w ci Br 1. 6943" 1. 6948 2. 630. 35 0 2. 640. 35 N// - O CHa Nz cri _nu ^ er N-fJ lJN N N 6N-"O 1. 6944 kl 1. 6949 0 2. 632. 35 t ßO 2. 640. 35 W I po fiC CHa O 'l Br a Br w N XNN ¢ N-N N-N N 1. 6945 N 1. 6950 2. 614. 34 2. 640. 35 N \ ZIP 0 Product 1. Ex. 2. Product m/z m/z w 1 w m/z m/z N-N N-N =f N 1. 6951 ci 1. 6956 Sr 2. 640. 35 N 2. 675. 23 ion t f N 4 S/N 6N-s 0 0 0 i er G Br J iN i l 1/N N_N N I N F N F 9. 6952 N-F F 1. 6957 N 2. 646. 36 2. 713. 39 S//40 F w O F _ _. er C B//f N-N nez N N-N 1. 6953 N 1. 6958 Q 2. 646. 36 2. 500. 27 zu NCS fez F'1 o O v0 F CI Br Br N N N-N O 'N-N 1. 6954 N 1. 6959 2. 648. 36 2. 562. 31 Ó zozo ci ci Br w d N > d f l N-N w 1. 6955 1. 6960 0 2. 654. 36 N, i° 2. 604. 33 =o \ r o CF6

TABLE 70 1. Ex. 2. Product,"Product"--"- m/z m/z -- N N N 1. 7001 1. 7006 2, 472, 26 N 2. 522. 29 N CF N CH3 zon bu 1. 7002 y 1. 7007 N _N< 2. 488. 27 N_N 2. 520. 29 N N 'i ! N\ Nw I N i Br N''O Br 1. 7003 1. 7008 2. 488. 27 2. 520. 29 A N N F Ntl N, 3 ry _, _J 1. 7004 1. 7009 2. 500. 27 | N_N N 2. 526. 29 N N N N\ I N\ I i N O i i xII Bt N'N' Br N \ N 1. 7010 N 2. 520. 29 N 2. 533. 29 N N NEZ I N Pædwl 1. Ex 2. _ _, 1. Ex 2. Product t. Ex. 2. Product 1. Ex. 2. m/z :/ Cbz ouzo Ber N 1. 7011 1. 7016 N_NAd 2. 536. 29 2. 538. 3 N N 6 U N I pYal N N l XCH, rz N9F 1. 7012 \ N° 1. 7017 N_NJ 2. 536. 29 vu 2. 540. 3 N N N l No.. -C' c, i Br o Br N Q 1. 7013 ; 1. 7018 NN 2. 536. 29 l NN 2. 542. 3 j N N ( N\ I N\ I F Br Br N 0 1. 7014 1. 7019 N_Nsfl 2. 536. 29 2. 544. 3 N N N I N I 0ICH, 0 t » tJb N 0 F Br B N' N p N F 1. 7015 v 1. 7020 2. 536. 29 N 2. 544. 3 N N ) 1 Fy7 1 Fx 7 Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z H N bu N 1. 7021"H 1. 7026 2. 548. 3 2. 566. 31 N N) I Nul __ _ N o- o _ _ = _ >CH3 O 1. 7022 1. 7027 V 2. 552. 3 V 2. 568. 31 NA N ci T !'"r cl o r---N-o 1. 7023 1. 7028 2. 552. 3 N, N 2. 572. 31 NA Nßl N N FI . __. _. s.. ; . r.. _ J'G F I N B Bt N-o 1. 7024 0 1. 7029 NA Nt1 N ; 3 Br NAO 2. 556. 31 NN 2. 576. 32 N-NU O 6 N N F'F / NU) Br Nô "° 1. 7025 s 1. 7030 2. 576. 32 2. 558. 31 N N N I N\ Product 1 l Product | 1. Ex 2. 1 m/z m/z a o 0 N-& ? N'v \ p 1. 7031 13rNN0CH3 1. 7036 ZON 2. 576. 32 N-N 2. 598. 33 -s _ çr N // cri a f il lui CI N \ SNsX 1. 7032 S < 1. 7037 2. 576. 32 2. 598. 33 N N N N cri Fuzz , cri i G N Ar NO 1. 7033 1. 7038 2. 590. 32 2. 610. 34 N-NU N-N N N N Br N N N lu N-N 1. 7034 2. 486. 27 N F F F /F "0 1. 7035 2. 594. 33 N-' /I nez

TABLE 71 Product 1 m/z 2. Product m/z 2 m/z m/z Br Br \N IN /Nz 1 1. 7101 1. 7106 l N 2. 474. 26 °=A 2. 522. 29 HC- H, \N H3C--\ CH3 N _. _., t Br Br /N N/N N 0 N 1, 7102 1. 7107 O N O N cC 2 : 488. 27 N 2. 522. 29 CH, FC Bu ber Br Br _N N N IN 1. 7103 0 N 1. 7108 N ou N 2. 500. 27 N 2. 526. 3 N F F -4 Bu ber N l CN 1. 7104 o= (N 1. 7109 O N N 2. 522. 29 2. 533. 29 Br Sr Chiral N N -\ -/*A "f NEZ 1. 7105 0= N 1. 7110 O N 0 N 2. 522. 29 N 2. 536. 29 H, C N N -|- Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z Choral N Nez 1. 7111 N 1. 7116 O N N 2. 536. 29 XN t 2. 538. 3 H ~ b\ N N CH, Bu ber CH N Br Br N-N /NN F N 1. 7112 =\ NA N 1. 7117 H N 2. 536. 29 t 2. 540. 3 H3C N Br Br CH3 \ N N-N Br -Br cp zon 1. 7113 N 1. 7118 N b 2. 536. 29 Cl\ N (2. 542. 3 4 CI N --- Br Br N---N NIN 1. 7114 NN 1. 7119 o N 2. 536. 29 N (2. 542. 3 N Cl--d N CI N Br N N-N (N_. N __ , N-N o N \N'1. 7115 0 N 1. 7120 2. 536. 3 2. 542. 3 c 0-d N N \ N H3C G Product 1. EX. 2. Product 1. Ex. 2. m/z m/z -- N N-N'N-N 1. 7126 /ND-X 1. 7126 2. 546. 3 N 2. 558. 31 < N 2. 546. 3 43 t 2. 558. 31 N _ t _ ~ N N-N N-N Cr ul N_N'/--_/,, NIN O= !. 7122 N -1. 7127 "2. 550. 3 H3c N 2. 550. 3 CH3 N Cl Cl, ho Br Br N N _ Br _ Br) 1. 7123 1. 7128 N N 2. 552. 3 2. 566. 31 O X tN H4H tN 0 0 OO Br Br _ bar / zon N O CRIN o N 1. 7124 1. 7129 N 2. 552. 3 N 2. 565. 31 N/Cl \N Br Br O-CH Br---Br N-N-N I % /N-N N 1. 7125 Fc-N 1. 7130 2. 556. 31 4 tN 2. 572. 31 cl- G CI Product 1 Ex. 2. product 1. Ex. 2. m/z m/z ---------- Bu ber qN N 1. 7131 =< N 1. 7136 2. 576. 32 2. 590. 32 xi F F ci Br Br -Bo __ _ _ u _ S N/I N/I (;}/44N O 4N nez O= (N 1. 7132 oC N 1. 7137 2. 576. 32 N 2. 590. 32 v _/vN I fizz ci ci ci /-A -f ?, -\ - Br sr I N/N N 1. 7133 0=< N N O N . _o 0 2. 576. 32 N/2. 598. 33 Xi \0 \N H3C-0 O-CH3 Br Br Br Br N N--, (/IL H3CO OCH3 N-N 1. 7134 l °= (4 1 7139 0== N 2. 584. 32 2. 598. 33 N N N Br Nazi -N /N 1. 7135 OC N 2. 585. 3 N Br-d N

TABLE 72 Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z N C, Br,, : N ci . _./A, \ N I 1 N N N 1. 7201 1. 7206 SN 2. 529. 29 tNa 2. 577. 32 I-tC 0 tA m ___ Cri 6r -/N/ N1 1. 7202 1. 7207 N, N xN 1. 7202 S 1. 7207 \ 2. 543. 3 2. 577. 32 0 0 L N-ci N N a \ N-C en Br 1. 7203, 1. 7208 t 2. 543. 3 2. 577. 32 cit e N i \-CH,'CH, _ , _ _ er N-a er a \N N IN WN N N N. 1. 7204 N 1. 7209 2. 555. 31 t 2. 581. 32 NF FX Cl ci N N'14 - ci a,'a N I N 1. 7205 N 1. 7210 N) | 1. 7205 1 > 1. 7210 t 12. 577. 32 2. 581. 32 F Product 1. Ex. 2. Product 1. Ex. 2. 1-X oF h 0e N \X m/z m/z N N VN"IN VNN S 1. 7211 2. 588. 32 2. 591. 33 zon N N N N 1. 7212 N"7. 2 1. 7212"\ 1. 7217 2. 588. 32 2. 593. 33 N O ON IN oc curai N-c, N-ci Br/N-CI I N'N 1. 7213 X 1. 7218 E XN 2. 591. 33 2. 593. 33 / C :/ oc N- . ChYel , N er N- lf zon 1. 7214 1. 7219 2. 591. 33 VN N 2. 593. 33 . N N N- O_cFS Q N-er N-ci Bru Iv. N ""1. 7215"'1. 7220 2. 591. 33 2. 595. 33 N 1 Ex ? 1 Ex ? Product, Product"," m/z m/z /\/l e 1. 7'-C. 7226 \ N I \ N I "1. 7221 \""1. 7226 2. 597. 33 2. 603. 33 N z ci Br -N N N I 1. 7227 2. 597. 33 2. 603. 33 CH, ci han N a /\/\ i ( I e\/° er N-a r TN I I 1. 7223" 1. 7228 2. 597. 33 2. 607. 33 ci Br,, Br N-ci a o __. /\/\ er"-a er N-c V eN I V iN I 1. 7224 \N"1. 7229 2. 599. 33 2. 607. 14 Br ci xi F F Ar/N-q-G Bu N/ 1. 7225 \N"1. 7230 2. 599. 33 2. 611. 34 __. fi F G 1 Fy ? 1 Fx ? -. m/z m/z Ber Br/N/Br/ N N 1. 7231 N/1. 7236 2. 613. 34 2. 631. 35 N, N F O Ber Br tJ-G CI Br N I 1. 7232 N/N 1. 7237 2. 605. 33 2. 631. 35 N F F cit a cul tL'C \ I F a ey/e N N 1. 7233 N 1. 7238 2. 621. 34 2. 631. 351 N \0 \-N X, a Non- Br -G & N_ p y NN N 1. 7234 1. 7239 BrSW4Nfa s Bra 2. 623. 34 2. 631. 35 zon mlz 0 cri, a''a / B mlz Bru N 1. 7240 2. 627. 34 2. 631. 35 N cul a Product 1. Ex. 2. Product 1. Ex. 2. Product m/z L... r B ci er jl_ a Br N N N 1. 7241 1. 7246 2. 639. 35 2. 653. 36 N zon \/ ber i a a Br N/Br I YC Nu N 1. 7242 1. 7247 , 2. 641. 35 <_NtN@F 2. 665. 37 2. 2. 665. 37 F3 N F F N O Br Br N Ns N 1. 7243 2. 645. 35 1. 7244 O N G G a a.. .... _ .. ....- Br I 1. 7244. 2. 541. 3 cri ber N 1. 7245 2. 649. 36 zon F F F TABLE 73 1. Ex. 2. 1. Ex. 2. 1. Ex. 2. Product mZ Product mZ Product m/z m/z m/z - , , , N/Q G N \ nN., I \NnN B N 1. 7301 1. 7306 1. 7311 2. 529. 29 ? O 2. 567. 31 2. 577. 32 NO p_'N O N N FS N Nx T N H, % N-f --mLo f : Nz 'v e a i N N' 1. 7302 1. 7307 A 1. 7312 Ç 2. 541. 3 2. 567. 31 St° 2. 577. 32 "-r i N/O O N \IF Iw I i ) a,-, a,-, B, r I, \ _ N \ \ I \-IJ v ° LJ I i N I N N N 1. 7303 1. 7308 1. 7313 2. 563. 13 NsG5° 2. 574. 32 2. 579. 32 | Na N) 2 N3 111 MY-0 N oc inti O i i sr (. e'I Br N\ \ N W N i a i a i . N. N 1. 7304 1. 7309 A 1. 7314 2. 563. 31 2. 574. 32 T 2. 579. 32 H3 ; » AN CH, t N'\ I/ N 0, cl, zon \ bar NN/Q N/a O I N 1. 7305 1. 7310 L 1. 7315 2. 563. 31 2. 577. 32 2. 579. 32 N_r 01, N Y N i, 0 N N 1 IN L, 'kACH, 1 Fy 7 1 Fx 2 1 Pv 7 Product 1. Ex. 2. Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z m/z e (I ber cl N N CI N 1 N.. N i a N ion N N 1. 7316 1. 7321 1. 7326 2. 581. 32 2. 585. 32 2. 599. 33 N O F NO/I N--f F v s F, 6 F --F N-1 N v \NN 1. 7317 1. 7322 1. 7327 2. 583. 32 2. 589. 32 9 2. 591. 33 HC _O N O/N ci foc N /V r, c i B, e s er N W /Cl/G N N/O N N N X 1. 7318 > 1. 7323 ruz 2. 583. 32 2. 591. 33 0 N"'O "T"T / )'0 -. er a e 'N 0 Ny0 N ^ i n BX 3 rSH B NkNS 1. 1. 7319 $ 1. 7324 1. 7329 2. 2. 583. 32 N 0 2. 593. 33 613. 34 N\ [9s o NOR y N N cri N_O, C, y'a o. cH cr, s er /\ Br W B N N G N N a N S a N N 1. 7320 1. 7325 A 1. 7330 2. 585. 32 2. 597. 33 2. 617. 34 N N Ci F OCH F F 1. Ex. 2. 1. Ex. 2. 1. Ex. 2. Product 1. Ex. 2. Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z m/z - N N a \a r\ N r N N N N N L 1. 7331 1. 7336 A 1. 73412. Ç 2. 599. 33 N 2. 617. 34 Y 635. 35 N N e F Cul F F s 4 s i 1 1 i 1 e, i ! - ' ) a"A i a I N/N \Q H tJ N N N 1. 7332 1. 7337 A 1. 7342 2. 591. 33 | W 2. 617. 34 2. 639. 35 N Nyo T". NO/lo" I o CH HC F F C I1G Bv v X BNkNe zu ' (CjL . jT'QJT N N i a \, a 1 H N r a zu N N 1. 7333 nu 1. 7338 1. 7343 2. 609. 33 2. 617. 34 2. 639. 35 N"'O N"'O Y N I \ OvCv \ \ I 0, nez . .. 1., s _. _.... _.... _.. w NN/Q /Q N 1. 7334 1. 7339 2. 613. 34 nu 2. 625. 34 Nyo N) aCl c., N J Br H1 B N "L N Ç 1. 7335 A 1. 7340 2. 617. 34 N 2. 631. 35 N N N F F a TABLE 74 . 1. Ex 2 Product 1. Ex. 2. Product 1. Ex. 2. m/z Product - « ex cl cl 'CI NN CI \ Cil wN 1. 7401 wN, 1. 7406 2. 515. 28 N 2. 563. 31 0CH, 0 S CH3 Ber N Cl Cl bu CI \ N"CI NN 1. 7402 N 1. 7407 2. 529. 291 2. 563. 31 /I \ I. \ I CHa N NCH3 N N i i (Br N i i CI NsAr AS Y 1. 7403 N 1. 7408 N 2. 541. 3 2. 567. 31 ULl JO 1 ~ I_ ___ ____ __ ___ __ F_. ___. _-- ___ i I g I E i AgZNAr Ngr C, N-N 1. 7404 Y N-N 1. 7409 2. 563. 13 N 2. 567. 31 aNJ4Na3 CNXN v N N r Br ex N N-N Cl \ N"G N'' N N 1. 7410 1. 7405 2. 563. 31 2. 574. 32 i o i CH N CF6 .. 1 E 2 Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z ------------------------------------------------ r Br f) Br Br Br cl N-N a N-N N 1. 7411 a eN N 1. 7416 2. 574. 32 2. 579. 32 N p "cl, Ber OU C, ChYnt Bf N cil N-N m$ mb 1. 7412 N 1. 7417 1 2. 577. 14 2. 579. 32 N/I O/I O''N N Zu Cul r N N 1. 7413 Cil N-N 1. 7418 aN 2. 577. 32 2. 579. 32 N I ole 0 \ r N N !/ Ber \) 'NN a N-N ci N N 1. 7414 1. 7419 2. 577. 32 0 2. 581. 32 C oH3C uNANX N''N C F N tCzNrS 6N N) P CF F Br r U % rN~N 1. 7415 N 1. 7420 2. 577. 32 N 2. 583. 32 -w ¢---C J w N N CI Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z sr 'I Br Cl Cl Zu-lu ci N-N 1. 7421 ci N-N 1. 7426 2. 583. 32 0--\ 2. 593. 33 0 cri 0 w o i ci w o i Cl aNXN ß Cl r bu CI NN ci N-N 1. 7422 1. 7427 2. 585. 32 2. 597. 33 F. 0 fez _. N _... _ Bu _N Y Y cul N 1. 7423 N 1. 7428 N F 2. 585. 32 ONC CF6 2. 591. 33 F o I' Br Br Cul r ff] Bu % i G N"CI NN 1. 7424 1. 7429 N 2. 589. 32 j 2. 609. 33 i o i "Nbr" N N C4 nu G N °' \ N N 1. 7425 1. 7430 ci3 2 591. 33 2. 613. 34 i o \ I \ I C'\ I NN I/ N N c Chl Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z N_r cil nô Cul CI 'NN f 1. 7431 N H3Cs 1. 7436 2. 617. 34 2. 639. 35 0 0, CH, O N F F \ I, CH3 N-nu N a w n, N _ Cl a N n) 1. 7432 J, 1. 7437 2* 617, 34 2. 639. 35 o i I o i Ber F 0 Br N a i. N r CI 'NN Y 1. 7433 1. 7438 2. 617. 34 N 2. 651. 36 ON F F /I F N N CI a Br s mA 1. 7434 N 2. 627. 34 NXNXBr _No' N cri 7436- N N 1. 7435 ou, 2. 631. 35 OHM CI'v'G TABLE75 1. Ex. 2. 1. Ex. 2. 1. Ex. 2. Product mz Product m 2. Product m/. m/z m/z m/z NIJ G G 1. 7501 1. 7506 1. 7511 2. 481. 26 N 2. 529. 29 N 2. 540. 3 0 CH. HC N 1 _. _L w. ______ L___ 9_ (N N j N ° 1 N -. _ NN /1 'IJ-N N-N G i G C N 1. 7507 1. 7512 S 2. 495. 27 tN', 2. 529. 29 ole 2. 540. 3 0 oN i 1 i A CH FC C6 N ci N N ci /\/-,., rv N_N I /p-N a a ! N a N f 1. 7503 1. 7513 N) 2. 495. 27 2. 529. 29 2. 543. 3 a O N o cri, -" Br rSc H, ' 1 tJ cnm I I N I I l N aWN ? N a<>N_N nez 1. 7504 1. 7509 1. 7514 2. 507. 28 oWN 2. 533. 29 2. 543. 3 b dF Sas Sur /\ r er i i I N I i v r_ -N v N-N N-N ce 1. 7505 1. 7510 ) =o 2. 529. 29 2. 533. 29 \ 2. 543. 3 Os/N N _ __-,, F F Product I Ex. 2. Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z m/z non l \ r N 1 s l \ r N-N 1. 7516 1. 7521 S 1. 7526 2. 543. 3 N N a Sr Br Bf Bt Br 3 IN s" s.' y I v N_N i W N_N CI G a < 1. 7517 s\ 1. 7522 1. 7527 2 5453 2. 549. 3 Was 2 557. 31 t"t sv > ou etc _ton 7N N N N N M N I v N-N, v1q v N-N NN 1 1 1. 7523 1. 7528 2.. 3 2. 549. 3 2. 559. 31 --t 0'-N Cl er Br WX N Non a N N a N X I 1. 7519 X 1. 7524 S 1. 7529 L 2. 545. 3 2. 551. 3) 2. 560. 31 O '0 =0 Hic ° c° Hz /\/rN I I N w NN a rv G H., H f 1. 7520 S 1. 7525 N) o z 1. 7530 F \/ I Product 1. Ex. 2. Product 1. Ex. 2. Product 1. Ex. 2. mlz mlz mlz - « t er m/z m/z m/z err N -N 1. 7531 1. 7536 1. 7541 N 2. 579. 32) 2. 583. 32 2. 605. 33 zon 0-chez 0 CF o rc-o o-cr a a Cco oai ci B ci N- /,, N I /N N I l-N q N q 1. 7532 1. 7537 1. 7542 2. 583. 32 2. 591. 33 2. 605. 33 0 o i Ber Buzz CA N/ 1 N N [ l-N \/ I I-N N i N_N G N G'°. a N 1. 7533 1. 7538 1. 7543 N) 2. 583. 32 tS. 2. 593. 33 2. 614. 34 N I FX SBr i FA /-N F \ p \. Q- Q F F Br Br N I I N N-lhl N-lht ZON 1. 7534 1. 7539 2. 583. 32 2. 597. 33 i i Q <-a F ci B /\ % G a 1. 7535 f 1. 7540 2. 583. 32 2. 601. 33 $ FtF - CA F F G F F

TABLE 76 1. Ex. 2. 1. Ex. 2. 1. Ex. 2. Product m. Product mZ Product m/z ex 6r / N// |91NyX g CI G-i oi N 1. 7601 1. 7606 1. 7611 i 2. 453. 25 X. 501. 28 N 2. 512. 28 N t4 N c o N N N, ., _.. _. ____.. _. _, _. __. ____B. _ _. -_-_ __, _. _.. ., _ j N/ j i i ! /w i aI j G G N, \ WX N 1. 7602 1. 7607 1. 7612 N 2. 467. 26 N 2. 501. 28 2. 512. 28 i N N N w er ar e p, rd V. f/ N N-N w N- ! J N--N G C CI N N N 1. 7608 1. 7613 N ; O 2. 467. 26 an 2. 501. 28 N N H3C aq, Hic Br r B, Chk. 1 /N 1 % N N N N N N w i CI CI CI N 1. 7604 1. 7609 1. 7614 j N 2. 479. 26 N 2. 505. 28 2. 515. 28 t b S | ai3 N Wt N G/n N//, N/ N/ dur I G N G v N_N G _ N_N N 1. 7605 1. 7610 1. 7615 N 2. 501. 28 t° 2. 505. 28 N 2. 515. 28 N N N-_o N O foc w F 1. Ex. 2. 1. Ex. 2. 1. Ex. 2. Product m/z Product 1 mxk2 Product 1m/Xf1 Product 1. Ex. 2. Product 1. Ex. 2. Product 1. Ex. 2. / mlz % N-N 1 f/I N-N N N N G 1. 7616 1. 7621 1. 7626 2. 515. 28 N 2. 521. 29 2. 527. 29 N __...-_ ---,.---. _ Ber' er N/ ! I, i/J ° N-N N G \ N 1. 7617 1. 7622 1. 7627 1 N 2. 517. 28 N 2. 521. 29 So 2. 529. 29 N C OC w A F,, ber _Nq'/ v i f/l \ i G IJ N G \ NN G N N N eNbN r 1 1. 7618 NS 1. 7623 NI N 1. 7628 N 2. 517. 28 N 2. 521. 29 V 2. 541. 3 NO N O N Cl6 r Br cri CH3 a N N I N \ N N CI \ N , j// n, N CI \ 1. 7619 i1. 7624 N 1. 7629 . iN 2. 517. 28 j'2. 523. 29 2. 545. 3 N F size O FI N Wu WX N-N v N"N CI 1 C3 c NS 1. 7620 N 1. 7625 N 1. 7630 2. 519. 29 N 2. 523. 29 2. 547. 3 N vs Rus p F Product 1. Ex. 2. Product 1. Ex. 2. Product 1. Ex. 2. , e. wP--- 4S w NN CI N 1. 7631 1. 7636 1. 7641 N 2. 551. 3 N 2. 555. 31 N 2. 577. 32 O N p_'N N W w bu ber PCR nu Br Br Br NEZ N 1 N / N-N N_N w N_N G CI \ CI 1. 7632 1. 7637 1. 7642 N 2. 555. 31 So 2. 563. 31 2. 577. 32 NO NO N O 1 1 FF F 1 \ S 1 W Br __ _ _ m G IJ N \ N-N G N 1. 7633 (N 1. 7638 L 2. 555. 31 So 2. 565. 31 F') b-Br o F 1 F F \, B Br Br Br _ N ° ci N 1. 7634 N 1. 7639 2. 555. 31 N 2. 569. 31 tF cíCI v Ber Ber ex i i w N-N N N 1. 7635 1. 7640 2. 555. 31 neo 2. 573. 32 O N N "f°'X a F FF TABLE 77 Product 1. Ex. 2. Product 1. Ex. 2. \ \ Br N Br G NN/ 1. 7701 N N 1. 7706 2. 481. 26 2. 529. 29 itc k kit CN C H'C N v s . _N Y ' Br N v Br N N \G N 1. 7702 1. 7707 N 2. 495. 27 2. 529. 29 HIC HIC N, a 1 / cl 1 an y N. B \ G N \ N N 1. 7703 N 1. 7708 2. 495. 27 2. 529. 29 N 0 C aN 1 H3C'N-0 CH CH3 bu ber PC I P Br N g v ci cl N N A NiN S 1. 7704 N 1. 7709 j N 2. 507. 28 2. 533. 29 N O , c N F V Pu 1 ci Nr Cl 1. 7705 N 1. 7710 2. 529. 29 2. 533. 29 - N c' F

TABLE 78 Product 'm. 2'Product /z m/z [ fil Cl -t-l G N" N 1. 7801 N 1. 7806 2. 507. 28 f 2. 555. 31 CNyNyCH3 OH Cn F sm o ,...... » , ex y'G NN CI \/NN l N 1. 7802 f 1. 7807 j 2. 521. 29 2. 555. 31 I N N H, C CH3 CH3 ! r of WN r N 1. 7803 N 1. 7808 C 2. 521. 29 2. 555. 31 N, NCI-l in i Br I er \ % i \ % CI \ NN CI N N 1. 7804 N 1. 7809 2. 533. 29 2. 559. 31 N N O F I/ , , r I Br 6NYN.,, o 6N y mA mb 1. 7805 N 1. 7810 (2. 555. 31 2. 559. 31 i 6N 6NyN,, a O \ I F Product 1. Ex. 2. Product 1. Ex. 2. w r fizz _ N N 1. 7811 N 1. 7816 2. 566. 31 2. 569. 31 N UNI 0 6N YN \ IN O/ C, yN _N --t L LJL a kv '1. 7892"1. 7817 2. 566. 31 2. 571. 31 N N N1/N (\ O I/O / 0 _ _,... _. __.... _ Chiral Ber a N-N' a N/Y G /NN I 1. 7813 N 1. 7818 N 2. 569. 31 tNyN 2. 571. 31 N'N W CF O'cit choral ber Choral Off cul G \ N"CI N' N N N 1. 7814 N 1. 7819 2. 569. 31 2. 571. 31 /N N 6NyN__o NyN,, aoCF ; N r XN r 0 Cbz B, bu CI \ NN G N-N N N 1. 7815 N 1. 7820 2. 569. 31 2. 573. 32 CF N II N/I N N I/F o Fi, C 0 1 Py 7 1 Fx 7 Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z r I er i i i i fn r fm Br CA L L LL N 1. 7821 N 1. 7826 2. 575. 32 2. 581. 32 Y O-O o CI / , 1 r I r , fA CI \ NN CI NN SXGN r N r N 1. 7822 '1. 7827 2. 575. 32 ton 2. 583. 32 N/N h r 14 r C4 CET ... _-.. fl f T S SJ0>, nA +, Ng N N N N N 1. 7823 N 1. 7828 2. 575. 32 2. 585. 32 N N \ t N N I CI C, _N cl SN N cl uN N r N 1. 7824 N 1. 7829 2. 577. 32 ßNyNX 2. 585. 32 6NyN 0 N/N/ o I N N Zu F I Br C'N a N-N Cl cl WN N G NN ru 1. 7825 N 1. 7830 2. 577. 32 2. 589. 32 y 6NyN F 0 C4 F 1 Ex 2 1 Fy ? Product 1. Ex. 2. Product 1. Ex 2. Product N N N 1. 7831 N 1. 7836 2. 591. 33 2. 609. 33 F F N N I N N/ F 0 0 r r--- XN \ NN G T N N 1. 7832 1. 7837 "2. 599. 33 2. 609. 33 ,-H - Non H F 'F ° H F a kN a 'L i 0 CI NN CI \ NN 1. 7833 N 1. 7838 2. 601. 33 A 2. 609. 33 yN'C OICH, 6N ZON °Cc y I/II '" O G Cl C, r ci r N r ru 1. 7834 1. 7839 A 2. 605. 33 NyNqa 2. 609. 33 N'N/I CI N'N G O O \ O I/ /r Cl CA o N CH, a N N S T"T N 1. 7835 N 1. 7840 2. 609. 33 C 2. 617. 34 NN, NN N N/N N 6 y Product''--Product''-- m/z m/z m/z m/z W N r N r CI NN G \ N N N 1. 7841 N 1. 7846 2. 619. 34 tNyN 2. 631. 35 ~ N N v Lez sur Cl N N CI NN GI N 1. 7842 N 1. 7847 2. 623. 34 2. 643. 35 /G F F N II N \ I (N II N O G I G bar ( G \\ NN WS I N N 1. 7843 dNtO 2. 519. 29 Neo I N a Nf CI 'NN I N 1. 7844 2. 627. 34 6NyN F F (N 1. 7845 0 F ZU Nz _razz 1. 7845 ! 1S 2. 631. 35 N'N/O O \ I H, C TABLE 79 Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z w , B N I i l SN 1. 7901 8,-N N 1. 7906 N_N 2. 477. 26 2. 504. 28 N j 1. 7902 N I I N I i Br N i 1. 7902 Bf, 1. 7907 2. 485. 27 NN/ 2. 505. 28 s zu / l 9 I% C Oc I 1. 7903 1. 7908 2, 2. 485. 27 N_N) 2. 507. 28 N _ _ N \ I-. /_ \ S N Ber N 1. 7904 <Se 1. 7904 e 1. 7909 N 2. 486. 27 N_N N 2. 509. 28 N N N N oH I Buzz N 1. 7905 1. 7910 N_NsrI 2. 495. 27 NN 2. 509. 28 N N 6 6 N\ I N I Product 1. Ex. 2. product 1. Ex. 2. m/z m/z m/z m/z 0 0 I Sr 1. 7911 Dr 1. 7916 2. 509. 28 N-N v 2. 523. 29 N N N NW I NW I Br N Br N G Br N Br N 1. 7912 N 2. 513. 28 N-N 2. 525. 29 N N\ I N I N CH, - II 'N- t r Br NN/ 1. 7913 1. 7918 2. 515. 28 N-N 2. 529. 29 N 6 N / Br N 9 U''-7914 - -79 N ' !. 7914 B, \ 1. 7919 N 2. 519. 29 N-N 2. 529. 29 N N N\ I N I /\ 0 Br ' N 1. 7915 N 1. 7920 2. 523. 29 N_N 2. 530. 29 N // N\ I N I 1 Ex 7 1 Fx 7 Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z m/z _- N ber su WNRX 1. 7921 WNNv 1. 7926 N_Nt 2. 530. 29 N-2. 547. 3 N NW I NW I _\... i Br Br 1. 7922 1. 7927 2. 535. 29 N N N cri Sr N CA Br N/ I \ NN/O Br N 1 7923 1. 7928 N 2. 547. 3 N NJ N NAZI ...."_ \ I F .. _.-.. F F Br 1. 7929 2. 2. 547. 3 N_Nf 2. 547. 3 N N Br N NW I Nw I Br N/ NN/P cH 1. 7925 SNNX 1. 7930 A 2. 547. 3 N N ? 2. 549. 3 N - NAZI Product 1. Ex. 2. Product 1. Ex. 2. I-p m/z m/z \ I i NN/ Br N 1. 7931 non 1. 7936 2. 555. 31 2. 567. 31 N N I ( Br ? B' _ » X v \ I/- ZON N i \ I s 1. 7932 B N"1. 7937 2. 555. 31 2. 567. 31 l N _ _ NA N I N N Ber Ber N N 1. 7933 1. 7938 2. 557. 31 NN 2. 569. 31 N N ') N N Br B N / Nz Br'N 1. 7934 N 1. 7939 N-N 2. 557. 31 2. 571. 31 N N N') Br ber N 0 N-N 1. 7935 N 1. 7940 N-N 2. 571. 31 N NEZ i 6 1 Py7 1 Py ? Product 1. m/z 2. Product 1. m/. 2. m/z m/z 0 s° D Sa0 Br N Br 1. 7941 1. 7946 N_N N 2. 608. 33 2. 471. 26 N NO 60 /O s Br Br N \ \ 1. 7942 1. 7947 N 2. 621. 34 N 2. 473. 26 N N N N Br Br N w N 1. 7943 N-N 1. 7948 nés 2. 443. 24 N 2. 483. 27 N N N N Br N'v Br C N-N 1. 7944 N-N 1. 7949 2. 457. 25 N 2. 485. 27 N\ I N I N N ^S' Br N,) D Br N'O \ \ \ N-N 1. 7945 1. 7950 2. 471. 26 N 2. 489. 27 0 0 Product I. Ex. 2. Product 1. eux. 2. m/z m/z F F Br N Br N chut3 N 1. 7951 N, N 1. 7956 N 2. 499. 27 f 2. 536. 29 N N Br N e ßF 1ii F F F CI-1 Bu N Br N 1. 7952 1. 7957 N-N 2. 513. 28 N_N 2. 539. 3 N N N //ON I N I _ N CH3 , 1. 7953 N 1. 7953 N, N 1. 7958 2. 514. 28 2. 541. 3 N N 0 0 i Br N Br N 1. 7954 1. 7959 2. 525. 29"N'2. 547. 3 1 1 N N I N I r\ C3 Br [. CI-t Br 1. 7955 1. 7960 2. 525. 29 N_Nr 2. 572. 31 N o6 N I N I TABLE 80 Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z Br Br N /NN/NN N \=< 1. 8001 N 1. 8006 2. 459. 25 N 2. 477. 26 H3C '\"' /-\ --< ?/-\ -" N N HC N 1. 80022. N 1. 80072 459. 25 N 485. 27 1 0-b CH, \N N CH3 N/ N -\ -/-\/" I Br Br N N N N N 1. 8003 N 1. 8008 2. 469. 26 N 2. 485. 27 1 tN tN N N N-N N bu bu N N N 1. 8004 N 1. 8009 2. 469. 26 A N 2. 48527 \ o \ s N N Br Br N /N NON 1. 8005 1. 8010 H, C 2. 473. 26 s N 2. 486. 27 1 HaC N/_S FC CH, bN Product 1. m/z 2. Product Br ____ _ ____-Br m/z m/z Sr bu , H S 1. Ex 2. puust 1 Ex 2- __J , JN-N ---/NN Ih 1. 8016 N 2. 493. 27 N 2. 495. 27 N bX N F Br Br zon N N N-N C _ _ Br N 1. 8012 N 1. 8017 N 2. 495. 27 N 2. 495. 27 Ho \\N \\N r.. .. _ F. Br. _ _-gr N uN I N--'/N-N 1. 8013 N N 1. 8018 /r'\y (1. 8013 N-. N\= 1. 8018 2. 495. 27 2. 502. 28 HO N N N N N-N 1. 8014 N 1. 8019 N 2. 495. 27 2. 502. 28 OU N H Br __ Br N C N/I /N_N ./\-/ 1. 8015 N N 1. 8020 2. 495. 27 2. 502. 28 \=/\ N N Product 1. Ex. 2. Product 1. Ex. 2. Br Br N I N/NN 1. 8021 N 1. 8026 N 2. 505. 28 N 2. 509. 28 N \N CH Br Br N (N_N/NN 1. 8022 N 1, 8027 2. 505. 28 N 2. 509. 28 tu \=/ Bu bu zon N N 1. 8023 N 1. 8028 N 2. 507. 28 N 2. 513. 28 ci Cl__b N N Br Br N N CH3 N N 1. 8024 N 1. 8029 N 2. 507. 28 N 2. 513. 28 CFi3 \\N \\N cl Br Br / // N_ N N N 1. 8025 1. 8030 N 2. 507. 28 N 2. 513. 28 o/ H3C \\N/\\N ce 1 Ex 2 1 Fx ? Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z Sur ber N /NN N-N N 1. 8031 N 1. 8036 A SF N 2. 515. 28 N 2. 523. 29 fus | C H3C tN Br Br Br Br \, N I N- /fJ_N/NN /O N 1. 8032 N 1. 8037 2. 519. 29 2. 525. 29 S-CH3 Br Br N N T Br Br I N I 1. 8033 N- 1. 8038 : N 2. 521. 29 N 2. 529. 29 Br Br bu ber ex bu N N N 1. 8034 N N-N 1. 8039 N 2. 523. 29 N 2. 529. 29 / Br Br to N N 0 Br Br m 9yNN CrN'N N 1. 8035 N 1. 8040 2. 523. 29 2. 530. 29 - I N aC N/I N OO Product 1-rEn/Xz 2-Product 1-m/XZ 2- m/z m/z Br Br N N 1. 8041 4 1. 8046 N 2. 530. 29 F 2. 547. 3 / I ZON cNH3 Br Br /N j I - NN 1. 8042 N 1. 8047 N 2. 535. 29 N 2. 544. 3 s ciel ce I Br Br N < N /Nz 1. 8043 NJ _ 1. 8048 2. 537. 3 N 2. 547. 3 \ / CH, cl bu ber CL3 CI Br Br N N/N N N 1. 8044 N 1. 8049 N 2. 547. 3 N 2. 547. 3 F CI CI Bu bu bu ber N/NN N 1. 8045 1. 8050 2. 547. 3 ci N 2. 547. 3 F y Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z Br Br -bof n s- N---<//N Xi 1. 8051 N 1. 8056 N 2. 548. 3 N 2. 569. 31 /b N N cl cri Ber 010 Br Bu N o \ I Br 1. 8052 -z a - N 2. 548. 3 2. 569. 31 ci nu CI N CI, N f . ClH Br N N NEZ 1. 8053 1. 8058 2. 54. 7. 3 2. 571. 31 vs H3C/ o Br Br N -fl/-N f X 1. 8054 rV N \=e 1. 8059 Ne 2. 555. 31 o se S 2. 608. 33 N -A 0 NEZ Br //N//N N 1. 8055 N 1. 8060 2. 553. 3 2. 621. 34 Cl G 1 Py ? 1 f=y 7 Product 1-Ex. 2. Product 1. Ex. 2. m/z m/z Br Br N N N N N N 1. 8061 N 1. 8066 2. 443. 24 N 2. 473. 26 0J \N N Br Br /I N NZ 1. 8062 Nid 1. 8067 d N 2. 457. 25 N 2. 483. 27 H H N N _ Bu ber Nz N N N 1. 8063 1. 8068 N 2. 471. 26 N 2. 485. 27 0'0' Br Br \ \ buzz bd /N I N Nz 1. 8064 N- 1. 8069 2. 471. 26 N 2. 483. 27 CH3 tN H3C (N Br Br Br Br N 1. 8065 N 1. 8070 N 2. 469. 26 N 2. 499. 27 rc _. ~ _ CH3 tN <D" 0" mt-'c. Product 2. ber N ; N N N /nid Fuzz 505. 2 Ber Ber N N 1. N- /\ N 1. 8072 F N F F Ber N- F F Bf N N N 1. N 8073 N 2. 537. 3 XI N Ber Ber Nez / 2. 8074 54. 7. 3 N TABLE81 Product 1. Ex. 2. Product 1. Ex. 2. Product 1. Ex. 2. m/zz m/z m/z Br N N N \ \N/N I Br t| n r n9 NvNsF Brt/Br uNSNNg 1. 8101 N 1. 8106 N 1. 8111 2. 510. 28 2. 528. 29 X 2. 542. 3 N N N \ : O \ e I HO K, G/Y CI HO HO % Br CA Br ei ci Br N7-INr 'c c J N 1. 8102 N 1. 8107 N 1. 8112 Nz 1. 8102 N) 1. 8107 N N 1. 81 12 2. 518. 28 2. 537. 3 2. 542. 3 N N f j N ^ BOGi t cilln------ ___.. ___. __. _________-. ______. __ _____-_______. __. at Br Br f W Br N NN/ No 1. 8103 A 1. 8108 1. 8113 2. 518. 28 2. 538. 3 8N 2. 548. 3 6N , s W I-CS a3 X BX3 BrX /I a i I a Bu over \/ N non N N 1. 8104 1. 8109 1. 8114 2. 2. 519. 2 C 2. 540. 3 2. 552. 3 N N N s Br o zon er, G \ er, \ aN N N, Nt N_Nt N, N ? 1. 8105 1. 8110 1. 8115 tu. 526. 29 S 2. 540. 3 C1 2. 554. 3 Na 9oCH3 a I I \1 1 Fx ? 1 Fx2 1 Pv 9 Product 1. Ex. 2. Product 1. Ex. 2. Product /G s-- m/z mlz / N 1. 1. 8116 1. 8121 (1. 8126 2. 556. 31 C 2. 580. 32 2. 588. 32 X X N ! i \ o G a Cue Ber Br _ \ Br 1. 8117 N 1. 8122 N 1. 8127 1. 8 2. 558. 31 t 2. 580. 32 2. 590. 32 N NJ \ N G I/G Br C4% cul ci CA I Br v Br N v ! w N N NiN N No 1. 8118"1. 8123"1. 8128 2. 562. 31 b a 2. 580. 32 t 2. 590. 32 bu N CA ber ber - __ __ . cri er I er N g \ w 1. 8119 d 1. 8125 Na 1. 8129 2. 580. 32 2. 580. 32 604. 33 N ci Elr F F F CI 1 Br er N 1. 8120 1. 8126 J 1. 8130 2. 580. 32 1 2. 588. 32 tX 2. 612. 34 N F F F 1. Ex. Product 1. Ex. 2. m/z Br))) er I N 1. 8131 2. 654. 36 Bu /I G.. Br t j) N 1. 8132 N6 2. 476. 26 1. 8133 2. 7 ("1. 8133 6"- 580. 32 a Ou N, N 8r N 1. 8134 1. 8134 2. 580. 32 N O TABLE 82 w Product 1-rEn/z 2-Product | 1-m/XZ 2- _ _. _ Cl 1 m/z mlz CI (\yin f \ N N \ /i 1. 8206 N 2. 488. 27 UN I 2. 512. 28 ON 0 0 ber ci C' I SS SX9 i N-N \ N- N 1. 8202 1. 8207 2. 496. 27 | X 12. 514. 28 ON bN, v Ber 3 _L. _T... ___- er.-.. _ non I C \YN N-N 1. 8203 1. 8208 2. 504. 28 Nß 2. 523. 29 l s a _ < ON S N, \/ nu N NON I N N \ N_ \ I I 1. 8204 1. 2. 504. 28 2. 524. 29 (/\-N N Br Br C'ab SNX SNS 1. 8205 N 1. 8210 2. 505. 28 ON 2. 526. 29 ON s- ; 1 Pv ? 1 Fy9 Product 1-Ex. 2. Product 1. Ex. 2. sr G sr m/z m/z / N-N N6N N N 1. 8211 > 1. 8216 2. 526. 29 N cl, 2. 534. 29 phi on 0 \46 i er G er 5-Nu N-\ N-N \ 0. 3 y 1. 8212 N 1. 8217 2. 528. 29 2. 537. 3 Cl3 N \__g ON Br Br Br ei Br N N N-N N-N N-N 1. 8213 N-N 1. 8218 N 2. 528. 29 N 2. 538. 3 w on O Ber -nu Cl N-N - S SNS N-N 1. 8214 N 1. 8219 NeÓ 2. 528. 29 So 2. 542. 3 On O Br Br ci N N N N-'b N 1. 8215 N 1. 8220 2. 532. 29 2. 2. 542. 3 G O 0 a o Product 1. Ex. 2. Product Ex. 2. n -Ho Su b 1 NX \ N \/N-\/ N-N _nu 1. 8221 1. 8226 N CH, 2. 544. 3 2. 551. 3 S/ N \ I , cN N _CI __ . _ _ dS_ 7'a 1 N N pu N 1. 8222 1. 8227 N 2. 544. 3 2. 554. 3 ON N s s \/i S \ Br G"'-'_.. _-__ _. _ CI non non N N_N N 1. 8223 N 1. 8228 ON 2. 548. 3 ON 2. 556. 31 O-CF6 \/ N o w non _. . _ _. _, . . w ex N N-. N \ i N N 1. 8224 1. 8229 2. 54. 8. 3 2. 566. 31 N N I F- i r G i ber a N N 1N-N SS SS N 1. 8225 1. 8230 2. 551. 3 N 2. 566. 31 /1 r/v N p HaC p F 1 Ex 9 1 Pv9 Product 1-Ex. 2. Product 1. Ex. 2. m/z m/z G Br _ _.. _-__ G N_N-\/, N N_N \ 1. 8231 N 1. 8236 F f 2. 566. 31 2. 568. 31 s _ \ I, F F F f-IC Br CI-_. _ CL N-r I 1 pu N 1. 8232 N-N 1. 8237 2. 566. 31 U X 2. 574. 32 ~9a _ Nu ci a Cl G r 5 NZ s N-N \ \/ N 1. 8233 1. 8238 2. 566. 31 N 2. 574. 32 a G Br Br zig _nu N N N 1. 8243 N 1. 8239 2. 566. 31 2. 576. 32 ON bu ... _ Br G Br N N 1. 8235 N 1. 8240 SNS SN i\ t N 1. 8235 N 1. 8240 \- 2. 566. 31 2. 576. 32 ci ber CI Br Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z S U X N<$ C \YN N-N 1. 8241 1. 8246 N 2. 576. 32 2. 590. 32 lp Br SNS S O-N bu C \rN CI r, i-N \ \ N N 1. 8242 N 1. 8247 2. 586. 32 ON 2. 598. 33 Br I ci N N N 1. 8243 1. 8248 2. 586. 32 2. 627. 34 s A N N 9 il I _. Br G G \ N N \ \ 1. 8244 1. 8249 2. 588. 32 2. 640. 35 /v Br C Br CI BE Br Cl pN N N-N N-N 1. 8245 N 1. 8250 \ 04 2. 590. 32 N 2. 462. 25 o N N Product t-Ex. 2. Product 1. Ex. 2. m/z m/z Br cl' N N \ N- cob N 1. 8251 N5_ 1. 8256 ON 2. 476. 26 2. 504. 28 N N b ar cl N N (er Non N N 1. 8252 ' 1. 8257 S 2. 490. 27 ON 2. 504. 28 N CH3 CH3 Br C'Br ci Br Br N6N N-N N-N N-N N 1. 8253 N 1. 8258 ON 2. 492. 27 ON 2. 508. 28 \-N \-N / X os Br Br Br G Br -N-N \-- N N-N N-N N 1. 8254 N 1. 8259 2. 492. 27 2. 530. 29 H r vs CL G r-N C'N r n 0 _ r ot N-N Non N 1. 8255 N 1. 8260 DN 2. 502. 28 0. 2. 533. 29 r \-N0 H H, C Product 1. Ex. 2. Product Ex. 2. m/z m/z Bu cri b 4 N-N 1. 8261 1. 8266 2. 544. 3 N 2. 560. 31 COB CA ci cC N b N-N N- 1. 8262 1. 8267 2. 546. 3 Nu 2. 566. 31 e, Ct _ _"r ( bu C N N-\ /N N \ N N-N N 1. 8263 N 1. 8268 2. 546. 3 N 2. 591. 33 X CH3 X cr etc Cbz dz N N 1. 8264 ON 1. 8269 2. 558. 31 Nu 2. 595. 33 \-N 0 Ber F f F -5--S s s B G r a N 1. 8265 1. 8270 U F 2. 558. 31 ß 2. 555. 31 0\-N I% c N e, c TABLE 83 Product 1. Ex. 2. Product 1. Ex. 2. 1. Ex. 2. Product m/z Br , N N N/CI N N/G N N/ N 1. 8301 N 1. 8306 1 1. 8311 465. 882 2. 491. 79 5012825 I HO N H3C) i (, S/I CH3 t aOH n BH B' N ;-Ty.' er I'Br I er \ \ l w i B Bv | GX nu 1. 8302 N 1. 8307 N 1. 8312 2. 2. 2. 465. 885 491. 792 501. 833 fc'Fc i \ 5 ou "1, I Br I Br fjj vs OH I BW3 N>NS I G NWNf B' N N G i NN' G N N 1. 8308 A 1. 8313 2. 2. I 2. 475. 827 492. 787 j N 510. 822 '""1'""1" 'ils nu bu i/ e v y Br I Br V N-N a N N NWN S NWNf NSoNe N 1. 8304 N 1. 8309 1. 8314 2. 2. 2. 4'79. 89 4gg, g46 F'°N 510. 821 v HIC . q H. r j' ! ; N IN 1. 8310 N 1. 8315 2. 2. 2. 1 483. 829 1 501. 826 , -" 511. 841 itc IN Ha S \ a _ _ I | 1 Ex 2. 1 Ex 2 1 Ex 2 1 Ex 2 w m/z mlz Product m/z N Br S zizi N N/G N/G 1. 8316 N 1. 8321 Nx 1-82326 N N_ 513. 855 519. 783 531. 804 HCI H, cY ri) rT"" cl 1 H3c IN N tcI < wi \ \ I N \ N/G N N N 1. 8317 N 1 8322 N 1. 8327 2. 2. 515. 832 519. 781 'N 531. 812 N ti'C/ i0/I,\ htC W Br I B/ B/I N N-N N\N/G N N G N N/G N) 8318"1. 8323 N HC'515. 832 525. 813 CV B' aq, S S N GX3 B NkNX Ge q CI N N/ca N N 1. 8319 N 1. 8324 N 1. 8329 2, 2. 2. H, C A 515. 837 HuC'N 529. 806 cCoNa 535. 831 N i li/o I 0. \O /w N N \_ y \ \_ y \ NCH N N/CI N N/G N 1. 8320" N 1. 8330 "1. 8325 CI-0 519. 782 H , N 2. 529. 81 H, c, N 541. 788 a S Product 1. Ex. 2. Product 1. Ex. 2. 1. Ex. 2. m/z m/z product rn/z Product N N \ C I N \Y I \ ° J ° N 1. 8331 N 1. 8336 1. 8341 2. 2., N 2. 543. 821 Hc) 554. 727 561. 838 OgStO a) i3 S q o w I I w a bu, cl er N N N\ \ N-CI N N/CI 1. 8332 N 1. 8337 N 1. 8342 2. 2. 2. 553. 797 554. 738 564. 714 N HC Ci F Br) F Nz W B e'I ar N W NN/G NN/G N 1. 8333 N 1. 8338 N 1. 8343 2. 2. 2 553. 796 N 554. 738 N 43 aX _ BX s N-N _ G _ a \ I a, e B'I N N N/a'rv/CI N N 1. 8334 N 1. 8339 N 1. 8344 2. 2. 2. 564. 72 \ N CN H, C / F F F G \ I CI Br FF Hc : , ci Br zon /G N N/G N N N "1. 8340 N 1. 8345 1. 8335 2. 554. 73 C, N o-"561. 8 r 36 573. 823 foc 1 Pv7 1 Ex 2 1 f=v 9 Product 1. Ex. 2. Product 1. Ex. 2. Product 1. Ex. 2. I s Bf v w N cri N N 1. 8346 N 1. 8351 NN/G 1, 8356 2. 2. N 2. 573. 735 529. 808 479. 856 i 5 c o H c /oH o i f i B NWNd N j0)'\. f) \ N j w NN/CI NN/CI N 1. 8352 N 2. 2. 2. N 575. 839 614. 763 511. 842 ¢S H3c N vs Er zon N nez N N G N N/CI 1. 8348 N 1. 8353 N 1. 8358 2. 2. N 577. 818 628. 727 520. 859 . I i Hoc cN No ci H, 60 H3C'r. _a HC, N"'ON y 0 e s w I Br a ber /a \ 6r G 1. 8349 N-1. 8354 N N 1. 8359 2. N 2. N 2. 577. 814 449. 857 533. 903 N, wu i o aCiN w I 'Nv \ I Bf N i a N er a NN/G \NiN 1. 8355 N 1. 8360 2. N 2. 2. d 585. 818 X 463. 867 N-cA 545. 823 I I u NU F 1 Ex ? Product,"' m/z if . "T 2. N -C 61 547. 909 | N_a1 H--- Foc ' ! Bu \ Nz N 1. 8362 2. 510. 817 N HN vs i zu a N 1. 8363 542. 833 O, rN Y - _.". r Bu N ci 1. 8364 2. N OH 573. 815 ou O N W Br a N 1. 8365 2. H3C 0 547. 798 HO HO TABLE 84 l P S-P 1. Ex 2. Sr Br N p bu Cl N 1. 8401 N-N ci 1. 8406 'N N 2. N 2. N 2. 2. cl N C. Br Br Br I Br I i W \ 'YT 'TT N-N cl 1. 8402 N-N cl 1. 8407 N 2. 2. 491. 883 517. 795 c s j kN, CH, -/ J Ns) XzCH3 N 1 Br Br N-N ci 1. 8403 N-N ci 1. 8408 i N 2 N 2. 501. 823 517. 799 s kN/k-N' N \ N I Br I Br N ? Cl 1. 8404 N cl 1. 8409 2. N 2. 501. 827 518. 796 0 s 6N N -qu sur nu N N 1. 8405 N T 1. 8410 N 1. o4U5 N 2. 505. 89 2. 525. 851 a N/ O XC H3 ; tNm Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z Ber 1. 8411 N 1. 8416 N N 2. 2. 527. 831 CH 539. 859 Nz N OH OH / Cl G 1. 8412 N, N 2. N 1. 8417 N N HO 527. 833 2. 541. 84 -8- , Cl cul zu s w sr N w 1. 8413 N A c 1. 8418 NEZ N, CH3 2. N 536. 833 0 541. 843 6N Br Br C, B N-N a 1. 8414 N-N cl 1. 8419 2. 2. N 536. 829 CH, 541. 843 , fi _ N \ bu \ \ Br N Br NN cl 1. 8415 4 1. 8420 Cul 2, N 2. N 537. 845 546. 786 cri i N CI 1 Ex 7 1 Ex 9 Product 1. Ex 2. Product 41. Ex 2. m/z M/z Br N 'N p I N 1. 8421 N-N ci 1. 8426 N'C, 546. 792 555. 817 o w cl O C, Br I Br N 2. 546. 79 N CH, 2. 557. 81 W w r" ! fr"r' 2. 54. 6. 79 N cN 2. 557. 81 G S N \ I N \ I Br Br Bu C, /Sr'VT 'TT N N ? Cl ! 1. 8423 N-N ci 1. 8428 /CH3 T 2. N 2. B 28 S A0 547. 854 CH, 557. 813 s i N N \ I bu ber Br/I Br/I N-N ci 1. 8424 N-N ci 1. 8429 N 2. N 2. 551. 826 561. 839 \ l bu ber i a S 1. 8425 cl 1. 8430 2. C, 555. 819 N 561. 833 Owl N 1 Ev 9 1 Py 9 Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z e Err Cl 1. 8431"1. 8436 N N 2. 2. 564. 841 6. 579. 794 ^'3 F F ex bu Bu ber N-N N-N cl 1. 8432 N-N 1. 8437 C, 2. N 2. N N 567. 795 1. 580. 738 ---2s S a Bu ber r Br f Br N 8433 N N 1. 8438 2. N 2. 1 A en-569. 823 aza 580. 732 N I N \ I G rip Bu Nez T 1. 8439 1. 8434 \- 1. 8434 N-- 1. 8439 Bru 2. N 2. 579. 797 580. 733 6 &) F F F a ex bu Br Nd, NX 1. 8435 BH 1. 8440 N z, N 2. 579. 796 580. 734 N 1 FF G F cl Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z Bu pu, N-1. 8446 2. N 2. cl 580. 726 590. 726 N Br r Cl Bu Br N-N a 1. 8442 N-N ci 1. 8447 2. N 2. 581. 805 590. 724 ex Cl, C N Br Br ''YT TT N-N cl 1. 8443 N-N cl 1. 8448 N 2. 2. 587. 844 599. 834 i' N ---t-----i--- Bu C, a N a 1. 8444') -' a 1. 8449 N 587. 835 599. 749 -- six N N ber Cl , N cl 1. 8445 1. 8450 NMP N'N 2. 2. tex 590. 723 N t 601. 854 N I N/I bu Product 1. 2. Product 1. Ex. 2. bu - S--w Br I N-N ci 1. 8451 1. 8456 N 2. 2. 0 603. 831 6N 640. 779 \0 r BrN E3r ri \ 1, NN/u NN/ 1. 8452 N ci 1. 8457 2. 603. 83 2. 6N 654. 746 \ I S 1 f r ex Br N\ T 1 NN/G N-N 1. 8453 1. 8458 N 2. 611. 83 N 2. -----,--.----i- Bu Br \ \ N-N_ ° 1. 8454 1. 8459 2. N 2. 555. 824 489. 879 N I N O oh ft s _ bu 6r N N G 1. 8455 N N/G 1. 8460 2. N 2. k 585. 817 503. 885 N KOH 0 D" Product 1. Ex. 2. Product 1. Ex. 2. 8r ber r 1. 8461 N'" 1. 8466 N 2. 2. bNn 505. 866 SCS 559. 919 t t Ber N A NN N s N w N_N 1. 8462 N 1. 8467 2. N 2. 507. 828 5 573. 925 nez Ber N-C I \. N \ _ \ (\ Jf. J I - 0 1. 8463 G ; f 1. 8468 2. 2. L w 537859 3. 878 1 N i i bu yN/G _ y w N-N 1. 8464 N-N ci 1. 8469 2. N 2. 546. 877 N 536. 831 N ci Bu cri CI Cl 1. 8465 1. 8470 2. N 2. 559. 921 N CH3 568. 843 "'N I/ 04 CH3 TABLE 85 -m . Product 1. Ex 2. _ Product 1. Ex 2. , mlz Bu r ci L/1. 85012. ! j 1. 8506 Hof N NV X HA HO n Br Cl 1. 8502 NN/CI 1. 8507 2. 381. 2 2. 323. 1 'Cl Oh _. ex/ Bu CI NN a 1. 8503 NN/CI 1. 8508 HO N 2. 443. 2 2. 365. 2 Ho N CH3 CH3 Br B r Cul ci N,' N 1. 8504 NN/CI 1. 8509 HO N 2. 457. 3 2. 379. 21 NEZ r J. Ber bu w v , x N 1. 8510 "1'2. 381. 21 N""0 1 Fy 7 1 Fv ? Product Ex. 2. Product 1. Ex. 2. m/z m/z BwNsX BwN9 Ber Br N ci 1. 8511 N-N ci 1. 8516 N 2. 381. 21 N 2. 409. 22 ly CH3 S 'dz CH, Br B y v y v i N N NN/CI . 8512 NN/CI 1. 8517 N 2. 393. 22 N 2. 411. 23 ou cl N-N a Br N \ \ NN/G i NN ci 1. 85131 N 1. 8518 s 2. 395. 22 X 2. 421. 23 N C yCit Br Br Br w v ! N CI N/CI N-N ci 1. 8514 N N ? Cl 1. 8519 N 2. 397. 22 N 2. 421. 23 N o ° ber i B il er 1 N/CI N-N a N 1. 8515 1. 8520 2. 407. 22 2. 425. 23 0 zu _ CH3 _ _ cC Product 1. Ex. 2. product 1. Ex. 2. m/z m/z Br zizi Be cl ? Cl s 1. 8521 N 1. 8526 1. 8521 N 1. 8526 2. 2. 429. 24 Jl 2. 445. 24 H, C NC Ber 1 Bu i N 1. 8522 1. 85272 2. 439. 24 N. 444.. 24 ci N-N_ ? Cl N 'N 'N w w y w N N/CI NN,/G N 1. 8523 N 1. 8528 2. 443. 24 2. 444. 24 0 r bu B Bu C, I N/G NN/CI 1. 8524 N 1. 8529 2. 443. 24 Tl 2. 446. 25 "lo y H3c 0) cl3 Bu \ \ TT rY N-N ci 1. 8525 NN ci 2. 445. 24 N 2. 457. 25 FI XI Cbz Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z a / Br v N \ /G \ \ N 1. 8531 NN OH ci 1. 8536 2. 480. 26 2. 431. 24 N i "aC F F F H3C Chiral Br Br Br I a 1. 8532 NN/CI 1. 8537 2. 483. 27 I) 2. 429. 24 N,,, ber Br n, s Chìral Br//Chiral bu N, N 1. 8533 NN/CI 1. 8538 2. 483. 27 oH 2. 397. 22 N i O a _ N-N I \ NN/G 1. 8539 2. 411. 23 N Br ___ NJ a Bu N/G N N 1. 8540 2. 411. 23 N N

1 Fy 9 1 Fx ? Product 1. Ex. 2. Product 1. Ex. 2. bu N- 1. 8541 1. 8547 N_Nsn <N) N 2. 432. 24 ci NN 2. 478. 26 N AN) I ci . _ _ _ BH Zon N 1. 8542 1. 8548 2. 433. 24 HOw 12. 498. 27 HO '° I Br N-NN ci N Br Cl Cl sur i ci N i N N CH3 1. 8543 Cl u N 1. 8549 2. 438. 24 2. 365. 1 \ ex CH, N1-11 CF ci N Br i\N N ? Cl <N< "1. 8545/1. 8549 2. 464. 26 N 2. 337. 1 N 0 cl CI Nez /G r// N 1. 8546 L N 1. 8550 2. 466. 26 N 2. 351. 1 N NH2 6 TABLE 86 ro 1. Ex. Product 1. Ex. 2. Product 1. Ex. 2. HO bu N N ber 0 N 1. 8601 N 2. 403. 22 N 2. 434. 24 W W N N bu N N r i i N N-N 1. 8602 N 1. 8607 YN_/Y. 407. 22 cN 2. 375. 21 N / IN H, c crt, z bu N 1 k. 1. 8603 1. 8608 N-N 2. 421. 23 N 2. 375. 21 N 0 kan N N AZIN N L 1 P' 1 1. 8604 } N> », Ng 1. 8604 W N_N/2 1. 8609 I fNN 2. 434. 24 cN 2. 391. 22 I 1. tu N 434. 24 2. 391. 22 N N 'I N N 16IN N zu Nz zu Br N % i 1. 8605 1. 8610 2. 391. 22 rN 2. 391. 22 N 2. 399. 22 N N N 1 Py ? 1 Fx ? Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z --v-b fjL c-\ Br . N % i N r N 2"417*23 2, 434"24 N N N N N ,. O Asz N er zN X r 'N-//1. 8612 1. 8617 N 2. 415. 23 YN 2. 446. 25 6N N N 6N IN .. _ __I r N i zon r r ) P Pr % 1. 8613"% 1. 8618 2. 428. 24 NN 2. 460. 25 ZON N __ I--I NJ N r N_Y__N-_C y 1. 8619 1. 8614 N 1. 8619 N 430. 430. 24 2. 459. 25 NZ IN N H, C , N 16N Fc ON 1. 8615 N 1. 8620 YNN/Y 2. 434. 24 2. 474. 26 RAZZ _N ION Product 1. Ex. 2. Product 1. Ex. 2. nez CHs/ HC \ HaC Br 9,, XI r w 1. 8621 NtzNg 1. 8626 2. 377. 21 2. 427. 23 N __ I--I" \ N w IN i cl, zon N r N r 1. 8622 N N 1. 8627 N-N 2. 406. 22 YN N 2. 431. 24 N 1N I Nz Ber nez Br 1. 8623 N-1. 8623 N 1. 8628 tloNN 1. 8623 NovzNgr 1. 8628 N 2. 412. 23 2. 446. 25 N N N 61N N ou j N N N 1. 8624 N__No 1, 8629 i N-N 2. 420. 23 XNN 2. 446. 25 N N 1, 61N Ber Nez Br r 1. 8625 1. 8630 2. 426. 23 "N 2. 407. 2 N N '1'1 N N Product 1. Ex. 2. Product 1. Ex. 2. m/z m/z ts Chiral \ CH3 C3 H, C-1-OH I-IC_ v OH r r N_lN-HC CH., N Nz 1. 8631 /N, N N 2. 407. 2 N 2. 475. 3 N HO OH Ho OH ber Bu er "1 Br k- N>s, 1. 8632 N'1. 8637 YNN 2. 409. 2 cN 2. 419. 2 N f N v \ IN cH3 cno-ai H' !-ION Br HA Br N ly N 1. 8638 2. 421. 2 N 2. 448. 2 N IN OH Chiral G, irat Q CCH3 Br N N'N N 1. 8634 YNN/Y 1. 8639 % rNN 2. 439. 2 (N 2. 379. 2 , 61N N N \ N OH Br Br /N, N Q er N-HO 1. 8640 N 1. 8635 N N 2. 455. 3 2. 437. 2 r N N N Product 1. Ex. 2. product 1. Ex. 2. m/z m/z A Br W Br fi :, C ttc NN I. ICN i i N 1. 8641-r/ 2. 415. 23 2. 423. 23 N \ \ O NH- Br ber sr N N i ow N\HwN0) < (9 Br 1. 8642 1. 8647 N 2. 443. 24 2. 430. 24 N N No¢wNoß N N Ber Br Br % i N N N-1. 8643'N-1. 8648 N 2. 416. 23 N 2. 437. 24 N / N N zu . __--. Ber ? i ¢9 N N 1. 8644 c'"% 1. 8649 N , 6N tN bN \ N \ N \... NN../ 1 Br Br N N\ N Br xi N 1. 8645 N, NI 1. 8650 N 2. 423. 23 2. 466. 26 N 6 Product 1. Ex. 2. Product m/z m/z "T Pr CL wl w 1. 8651 1. 8656 N-N 2. 423. 23 2. 445. 24 N N Zizi \ N \ N /I 1 G I \ 'N i N 1. 8652 N'1. 8657 2. 425. 23 2. 445. 24 N _I IN IN CF4, r"f 6 clip N-N/2. 451. 25 2. 437. 24 YNN 2. 451. 25 bN bN N N \/ N Oye o NN 1. 8654 1. 8659 YN_N//2. 437. 24 N 2. 476. 26 I NN 6N N Ber \ IN IN F I F F Br N_N 1. 8655 1. 8660 YNN 2. 437. 24 eN N 2. 479. 26 N N 6 6 N N Product 1. Ex. 2. m/z Bu F F Y \ F N zon F ber a I I Br N, N-1. 8662 N 2. 479. 26 N a G I N