WSGR Docket No.62619-716.601 AKT1 MODULATORS CROSS-REFERENCE [001] This application claims the benefit of US Provisional Application No.63/383,008 filed November 09, 2022, which is incorporated herein by reference in its entirety. BACKGROUND [002] AKT is a protein kinase and mediates cell survival and proliferation by inhibiting pathways which promotes apoptosis. AKT signaling cascade dysfunction is observed in several cancer types and may be associated with tumor aggressiveness. Additionally, malfunction of AKT typically lead to enhanced proliferation, growth, survival, and resistance to apoptosis. Pharmaceutical agents with the ability to modulate AKT1 activity would be useful in the treatment of disease, such as cancer. BRIEF SUMMARY OF THE INVENTION [003] Provided herein are inhibitors of AKT1, pharmaceutical compositions comprising said inhibitory compounds, and methods for using said inhibitory compounds for the treatment of disease. [004] One embodiment provides a compound having the structure of Formula (I), or a pharmaceutically acceptable salt or solvate thereof: wherein: Z ¹ is N, C-H, or C-R ³ ; Z ² is N, C-H, or C-R ⁴ ; X is -C(O)-, or -S(O)2-; R ¹ is selected from hydrogen, halogen, -CN, optionally substituted C1-C6 alkyl, optionally substituted aryl, or optionally substituted heteroaryl; R ² is selected from hydrogen, halogen, -CN, optionally substituted C1-C6 alkyl, optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted C3-C10 carbocyclyl, or optionally substituted heteroaryl; R ³ is selected from halogen, -CN, optionally substituted C1-C6 alkyl, or optionally substituted aryl; WSGR Docket No.62619-716.601 R ⁴ is selected from halogen, -CN, optionally substituted C1-C6 alkyl, or optionally substituted aryl; R ⁵ and R ⁶ are each independently hydrogen, deuterium, halogen, -OH, or optionally substituted C1-C6 alkyl; or R ⁵ and R ⁶ together form an oxo; or R ⁵ and R ⁶ join together to form a carbocycle or heterocycle; L is selected from -N(R ⁷ )-, or a divalent radical selected from: WSGR Docket No.62619-716.601 wherein the asterisk (*) indicates the bond to the X group; a is 0, 1, 2, 3, or 4; b is 0, 1, 2, 3, or 4; c is 1, 2, 3, or 4; d is 1, 2, 3, or 4; e is 0, 1, 2, 3, or 4; f is 0, 1, 2, 3, or 4; provided that e and f are not both 0; g is 0, 1, 2, 3, or 4; provided that e and g are not both 0; h is 0, 1, 2, 3, or 4; provided that g and h are not both 0; and provided that f and h are not both 0; m is 0, 1, or 2; n is 1, 2, or 3 R ⁷ is hydrogen, optionally substituted C1-C6 alkyl, optionally substituted C3-C7 cycloalkyl, optionally substituted heterocyclyl, or R ⁷ and V join together to form a carbocycle or heterocycle; V is selected from: each R ⁸ , R ⁹ , R ¹⁰ , and R ¹¹ is independently selected from hydrogen, F, CN, optionally substituted C1-C6 alkyl, optionally substituted aryl, and optionally substituted alkoxy. [005] One embodiment provides a compound having the structure of Formula (Ia), or a pharmaceutically acceptable salt or solvate thereof: WSGR Docket No.62619-716.601 wherein: Z ¹ is N, C-H, or C-R ³ ; Z ² is N, C-H, or C-R ⁴ ; R ¹ is selected from hydrogen, halogen, -CN, optionally substituted C1-C6 alkyl, optionally substituted aryl, or optionally substituted heteroaryl; R ² is selected from hydrogen, halogen, -CN, optionally substituted C1-C6 alkyl, optionally substituted aryl, or optionally substituted heteroaryl; R ³ is selected from halogen, -CN, optionally substituted C1-C6 alkyl, or optionally substituted aryl; R ⁴ is selected from halogen, -CN, optionally substituted C1-C6 alkyl, or optionally substituted aryl; R ⁵ and R ⁶ are each independently hydrogen, deuterium, halogen, -OH, or optionally substituted C1-C6 alkyl; or R ⁵ and R ⁶ together form an oxo; or R ⁵ and R ⁶ join together to form a carbocycle or heterocycle; L is selected from -N(R ⁷ )-, or a divalent radical selected from: WSGR Docket No.62619-716.601 wherein the asterisk (*) indicates the bond to the X group; a is 0, 1, 2, 3, or 4; b is 0, 1, 2, 3, or 4; c is 1, 2, 3, or 4; d is 1, 2, 3, or 4; e is 0, 1, 2, 3, or 4; f is 0, 1, 2, 3, or 4; provided that e and f are not both 0; g is 0, 1, 2, 3, or 4; provided that e and g are not both 0; h is 0, 1, 2, 3, or 4; provided that g and h are not both 0; and provided that f and h are not both 0; m is 0, 1, or 2; n is 1, 2, or 3 WSGR Docket No.62619-716.601 R ⁷ is hydrogen, optionally substituted C1-C6 alkyl, optionally substituted C3-C7 cycloalkyl, or optionally substituted heterocyclyl; X-V is selected from: each R ⁸ , R ⁹ , R ¹⁰ , and R ¹¹ is independently selected from hydrogen, F, CN, optionally substituted C1-C6 alkyl, optionally substituted aryl, and optionally substituted alkoxy. [006] One embodiment provides a pharmaceutical composition comprising a compound of Formula (I), or pharmaceutically acceptable salt or solvate thereof, and at least one pharmaceutically acceptable excipient. [007] One embodiment provides a method of treating a disease or disorder in a patient in need thereof comprising administering to the patient a compound of Formula (I), or pharmaceutically acceptable salt or solvate thereof. Another embodiment provides the method wherein the disease or disorder is cancer. INCORPORATION BY REFERENCE [008] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference for the specific purposes identified herein. DETAILED DESCRIPTION OF THE INVENTION [009] As used herein and in the appended claims, the singular forms "a," "and," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "an agent" includes a plurality of such agents, and reference to "the cell" includes reference to one or more cells (or to a plurality of cells) and equivalents thereof known to those skilled in the art, and so forth. When ranges are used herein for physical properties, such as molecular weight, or chemical properties, such as chemical formulae, all combinations and subcombinations of ranges and specific embodiments therein are intended to be included. The term "about" when referring to a number or a numerical range means that the number or numerical range referred to is an approximation within experimental variability (or within statistical experimental error), and thus the number or numerical range, in some instances, will vary between 1% and 15% of the stated number or numerical range. The term "comprising" (and related terms such as "comprise" or "comprises" or "having" or "including") is not intended to exclude that in other certain embodiments, for example, an embodiment of any composition of matter, composition, method, or process, or the like, described herein, "consist of" or "consist essentially of" the described features. WSGR Docket No.62619-716.601 Definitions [0010] As used in the specification and appended claims, unless specified to the contrary, the following terms have the meaning indicated below. [0011] "Amino" refers to the –NH2 radical. [0012] "Cyano" refers to the -CN radical. [0013] "Nitro" refers to the -NO2 radical. [0014] "Oxa" refers to the -O- radical. [0015] "Oxo" refers to the =O radical. [0016] "Thioxo" refers to the =S radical. [0017] "Imino" refers to the =N-H radical. [0018] "Oximo" refers to the =N-OH radical. [0019] "Hydrazino" refers to the =N-NH2 radical. [0020] "Alkyl" refers to a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containing no unsaturation, having from one to fifteen carbon atoms (e.g., C1-C15 alkyl). In certain embodiments, an alkyl comprises one to thirteen carbon atoms (e.g., C1-C13 alkyl). In certain embodiments, an alkyl comprises one to eight carbon atoms (e.g., C ₁ -C ₈ alkyl). In other embodiments, an alkyl comprises one to five carbon atoms (e.g., C1-C5 alkyl). In other embodiments, an alkyl comprises one to four carbon atoms (e.g., C1- C4 alkyl). In other embodiments, an alkyl comprises one to three carbon atoms (e.g., C1-C3 alkyl). In other embodiments, an alkyl comprises one to two carbon atoms (e.g., C ₁ -C ₂ alkyl). In other embodiments, an alkyl comprises one carbon atom (e.g., C1 alkyl). In other embodiments, an alkyl comprises five to fifteen carbon atoms (e.g., C5-C15 alkyl). In other embodiments, an alkyl comprises five to eight carbon atoms (e.g., C ₅ -C ₈ alkyl). In other embodiments, an alkyl comprises two to five carbon atoms (e.g., C2-C5 alkyl). In other embodiments, an alkyl comprises three to five carbon atoms (e.g., C3-C5 alkyl). In other embodiments, the alkyl group is selected from methyl, ethyl, 1-propyl (n-propyl), 1-methylethyl (iso-propyl), 1-butyl (n-butyl), 1-methylpropyl (sec-butyl), 2-methylpropyl (iso-butyl), 1,1-dimethylethyl (tert-butyl), 1-pentyl (n-pentyl). The alkyl is attached to the rest of the molecule by a single bond. Unless stated otherwise specifically in the specification, an alkyl group is optionally substituted by one or more of the following substituents: halo, cyano, nitro, oxo, thioxo, imino, oximo, trimethylsilanyl, -OR ^a , -SR ^a , -OC(O)-R ^a , -N(R ^a )2, -C(O)R ^a , -C(O)OR ^a , -C(O)N(R ^a )2, - N(R ^a )C(O)OR ^a , -OC(O)-N(R ^a ) ₂ , -N(R ^a )C(O)R ^a , -N(R ^a )S(O) _t R ^a (where t is 1 or 2), -S(O) _t OR ^a (where t is 1 or 2), -S(O)tR ^a (where t is 1 or 2) and -S(O)tN(R ^a )2 (where t is 1 or 2) where each R ^a is independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), fluoroalkyl, carbocyclyl (optionally substituted with halogen, hydroxy, WSGR Docket No.62619-716.601 methoxy, or trifluoromethyl), carbocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl). In certain embodiments, an optionally substituted alkyl is a haloalkyl. In other embodiments, an optionally substituted alkyl is a fluoroalkyl. In other embodiments, an optionally substituted alkyl is a -CF3 group. [0021] "Alkoxy" refers to a radical bonded through an oxygen atom of the formula –O-alkyl, where alkyl is an alkyl chain as defined above. [0022] "Alkenyl" refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one carbon-carbon double bond, and having from two to twelve carbon atoms. In certain embodiments, an alkenyl comprises two to eight carbon atoms. In other embodiments, an alkenyl comprises two to four carbon atoms. The alkenyl is attached to the rest of the molecule by a single bond, for example, ethenyl (i.e., vinyl), prop-1-enyl (i.e., allyl), but-1-enyl, pent-1-enyl, penta-1,4-dienyl, and the like. Unless stated otherwise specifically in the specification, an alkenyl group is optionally substituted by one or more of the following substituents: halo, cyano, nitro, oxo, thioxo, imino, oximo, trimethylsilanyl, -OR ^a , -SR ^a , -OC(O)-R ^a , -N(R ^a )2, -C(O)R ^a , -C(O)OR ^a , -C(O)N(R ^a )2, - N(R ^a )C(O)OR ^a , -OC(O)-N(R ^a )2, -N(R ^a )C(O)R ^a , -N(R ^a )S(O)tR ^a (where t is 1 or 2), -S(O)tOR ^a (where t is 1 or 2), -S(O) _t R ^a (where t is 1 or 2) and -S(O) _t N(R ^a ) ₂ (where t is 1 or 2) where each R ^a is independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), fluoroalkyl, carbocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), carbocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl). [0023] "Alkynyl" refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one carbon-carbon triple bond, having WSGR Docket No.62619-716.601 from two to twelve carbon atoms. In certain embodiments, an alkynyl comprises two to eight carbon atoms. In other embodiments, an alkynyl comprises two to six carbon atoms. In other embodiments, an alkynyl comprises two to four carbon atoms. The alkynyl is attached to the rest of the molecule by a single bond, for example, ethynyl, propynyl, butynyl, pentynyl, hexynyl, and the like. Unless stated otherwise specifically in the specification, an alkynyl group is optionally substituted by one or more of the following substituents: halo, cyano, nitro, oxo, thioxo, imino, oximo, trimethylsilanyl, -OR ^a , -SR ^a , -OC(O)-R ^a , -N(R ^a )2, -C(O)R ^a , -C(O)OR ^a , - C(O)N(R ^a ) ₂ , -N(R ^a )C(O)OR ^a , -OC(O)-N(R ^a ) ₂ , -N(R ^a )C(O)R ^a , -N(R ^a )S(O) _t R ^a (where t is 1 or 2), -S(O)tOR ^a (where t is 1 or 2), -S(O)tR ^a (where t is 1 or 2) and -S(O)tN(R ^a )2 (where t is 1 or 2) where each R ^a is independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), fluoroalkyl, carbocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), carbocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl). [0024] "Alkylene" or "alkylene chain" refers to a straight or branched divalent hydrocarbon chain linking the rest of the molecule to a radical group, consisting solely of carbon and hydrogen, containing no unsaturation, and having from one to twelve carbon atoms, for example, methylene, ethylene, propylene, n-butylene, and the like. The alkylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. The points of attachment of the alkylene chain to the rest of the molecule and to the radical group are through one carbon in the alkylene chain or through any two carbons within the chain. In certain embodiments, an alkylene comprises one to eight carbon atoms (e.g., C1-C8 alkylene). In other embodiments, an alkylene comprises one to five carbon atoms (e.g., C ₁ -C ₅ alkylene). In other embodiments, an alkylene comprises one to four carbon atoms (e.g., C1-C4 alkylene). In other embodiments, an alkylene comprises one to three carbon atoms (e.g., C1-C3 alkylene). In other embodiments, an alkylene comprises one to two carbon atoms (e.g., C ₁ -C ₂ alkylene). In other embodiments, an alkylene comprises one carbon atom (e.g., C ₁ alkylene). In other embodiments, an alkylene comprises five to eight carbon atoms (e.g., C5-C8 alkylene). In other embodiments, an alkylene comprises two to five carbon atoms (e.g., C2-C5 alkylene). In other embodiments, an alkylene comprises three to five carbon atoms (e.g., C ₃ -C ₅ WSGR Docket No.62619-716.601 alkylene). Unless stated otherwise specifically in the specification, an alkylene chain is optionally substituted by one or more of the following substituents: halo, cyano, nitro, oxo, thioxo, imino, oximo, trimethylsilanyl, -OR ^a , -SR ^a , -OC(O)-R ^a , -N(R ^a ) ₂ , -C(O)R ^a , -C(O)OR ^a , - C(O)N(R ^a )2, -N(R ^a )C(O)OR ^a , -OC(O)-N(R ^a )2, -N(R ^a )C(O)R ^a , -N(R ^a )S(O)tR ^a (where t is 1 or 2), -S(O) _t OR ^a (where t is 1 or 2), -S(O) _t R ^a (where t is 1 or 2) and -S(O) _t N(R ^a ) ₂ (where t is 1 or 2) where each R ^a is independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), fluoroalkyl, carbocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), carbocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl). [0025] "Alkenylene" or "alkenylene chain" refers to a straight or branched divalent hydrocarbon chain linking the rest of the molecule to a radical group, consisting solely of carbon and hydrogen, containing at least one carbon-carbon double bond, and having from two to twelve carbon atoms. The alkenylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. In certain embodiments, an alkenylene comprises two to eight carbon atoms (e.g., C2-C8 alkenylene). In other embodiments, an alkenylene comprises two to five carbon atoms (e.g., C2-C5 alkenylene). In other embodiments, an alkenylene comprises two to four carbon atoms (e.g., C ₂ -C ₄ alkenylene). In other embodiments, an alkenylene comprises two to three carbon atoms (e.g., C2-C3 alkenylene). In other embodiments, an alkenylene comprises two carbon atoms (e.g., C2 alkenylene). In other embodiments, an alkenylene comprises five to eight carbon atoms (e.g., C ₅ -C ₈ alkenylene). In other embodiments, an alkenylene comprises three to five carbon atoms (e.g., C3-C5 alkenylene). Unless stated otherwise specifically in the specification, an alkenylene chain is optionally substituted by one or more of the following substituents: halo, cyano, nitro, oxo, thioxo, imino, oximo, trimethylsilanyl, -OR ^a , -SR ^a , -OC(O)-R ^a , -N(R ^a )2, -C(O)R ^a , -C(O)OR ^a , -C(O)N(R ^a )2, - N(R ^a )C(O)OR ^a , -OC(O)-N(R ^a )2, -N(R ^a )C(O)R ^a , -N(R ^a )S(O)tR ^a (where t is 1 or 2), -S(O)tOR ^a (where t is 1 or 2), -S(O) _t R ^a (where t is 1 or 2) and -S(O) _t N(R ^a ) ₂ (where t is 1 or 2) where each R ^a is independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), fluoroalkyl, carbocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), carbocyclylalkyl (optionally substituted with halogen, hydroxy, WSGR Docket No.62619-716.601 methoxy, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl). [0026] "Alkynylene" or "alkynylene chain" refers to a straight or branched divalent hydrocarbon chain linking the rest of the molecule to a radical group, consisting solely of carbon and hydrogen, containing at least one carbon-carbon triple bond, and having from two to twelve carbon atoms. The alkynylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. In certain embodiments, an alkynylene comprises two to eight carbon atoms (e.g., C2-C8 alkynylene). In other embodiments, an alkynylene comprises two to five carbon atoms (e.g., C ₂ -C ₅ alkynylene). In other embodiments, an alkynylene comprises two to four carbon atoms (e.g., C2-C4 alkynylene). In other embodiments, an alkynylene comprises two to three carbon atoms (e.g., C2-C3 alkynylene). In other embodiments, an alkynylene comprises two carbon atoms (e.g., C ₂ alkynylene). In other embodiments, an alkynylene comprises five to eight carbon atoms (e.g., C5-C8 alkynylene). In other embodiments, an alkynylene comprises three to five carbon atoms (e.g., C3-C5 alkynylene). Unless stated otherwise specifically in the specification, an alkynylene chain is optionally substituted by one or more of the following substituents: halo, cyano, nitro, oxo, thioxo, imino, oximo, trimethylsilanyl, -OR ^a , -SR ^a , -OC(O)-R ^a , -N(R ^a )2, -C(O)R ^a , -C(O)OR ^a , - C(O)N(R ^a ) ₂ , -N(R ^a )C(O)OR ^a , -OC(O)-N(R ^a ) ₂ , -N(R ^a )C(O)R ^a , -N(R ^a )S(O) _t R ^a (where t is 1 or 2), -S(O)tOR ^a (where t is 1 or 2), -S(O)tR ^a (where t is 1 or 2) and -S(O)tN(R ^a )2 (where t is 1 or 2) where each R ^a is independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), fluoroalkyl, carbocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), carbocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl). WSGR Docket No.62619-716.601 [0027] "Aryl" refers to a radical derived from an aromatic monocyclic or multicyclic hydrocarbon ring system by removing a hydrogen atom from a ring carbon atom. The aromatic monocyclic or multicyclic hydrocarbon ring system contains only hydrogen and carbon from five to eighteen carbon atoms, where at least one of the rings in the ring system is fully unsaturated, i.e., it contains a cyclic, delocalized (4n+2) p–electron system in accordance with the Hückel theory. The ring system from which aryl groups are derived include, but are not limited to, groups such as benzene, fluorene, indane, indene, tetralin and naphthalene. Unless stated otherwise specifically in the specification, the term "aryl" or the prefix "ar-" (such as in "aralkyl") is meant to include aryl radicals optionally substituted by one or more substituents independently selected from optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, halo, cyano, nitro, -R ^b -OR ^a , -R ^b -OC(O)-R ^a , -R ^b -OC(O)-OR ^a , -R ^b - OC(O)-N(R ^a )2, -R ^b -N(R ^a )2, -R ^b -C(O)R ^a , -R ^b -C(O)OR ^a , -R ^b -C(O)N(R ^a )2, -R ^b -O-R ^c -C(O)N(R ^a )2, - R ^b -N(R ^a )C(O)OR ^a , -R ^b -N(R ^a )C(O)R ^a , -R ^b -N(R ^a )S(O)tR ^a (where t is 1 or 2), -R ^b -S(O)tR ^a (where t is 1 or 2), -R ^b -S(O) _t OR ^a (where t is 1 or 2) and -R ^b -S(O) _t N(R ^a ) ₂ (where t is 1 or 2), where each R ^a is independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), fluoroalkyl, cycloalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), cycloalkylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), each R ^b is independently a direct bond or a straight or branched alkylene or alkenylene chain, and R ^c is a straight or branched alkylene or alkenylene chain, and where each of the R ^a , R ^b , or R ^c substituents is unsubstituted unless otherwise indicated. [0028] "Aralkyl" refers to a radical of the formula -R ^c -aryl where R ^c is an alkylene chain as defined above, for example, methylene, ethylene, and the like. The alkylene chain part of the aralkyl radical is optionally substituted as described above for an alkylene chain. The aryl part of the aralkyl radical is optionally substituted as described above for an aryl group. [0029] "Aralkenyl" refers to a radical of the formula –R ^d -aryl where R ^d is an alkenylene chain as defined above. The aryl part of the aralkenyl radical is optionally substituted as described above for an aryl group. The alkenylene chain part of the aralkenyl radical is optionally substituted as defined above for an alkenylene group. WSGR Docket No.62619-716.601 [0030] "Aralkynyl" refers to a radical of the formula -R ^e -aryl, where R ^e is an alkynylene chain as defined above. The aryl part of the aralkynyl radical is optionally substituted as described above for an aryl group. The alkynylene chain part of the aralkynyl radical is optionally substituted as defined above for an alkynylene chain. [0031] "Aralkoxy" refers to a radical bonded through an oxygen atom of the formula -O-R ^c -aryl where R ^c is an alkylene chain as defined above, for example, methylene, ethylene, and the like. The alkylene chain part of the aralkyl radical is optionally substituted as described above for an alkylene chain. The aryl part of the aralkyl radical is optionally substituted as described above for an aryl group. [0032] "Carbocyclyl" refers to a stable non-aromatic monocyclic or polycyclic hydrocarbon radical consisting solely of carbon and hydrogen atoms, which includes fused or bridged ring systems, having from three to fifteen carbon atoms. In certain embodiments, a carbocyclyl comprises three to ten carbon atoms. In other embodiments, a carbocyclyl comprises five to seven carbon atoms. The carbocyclyl is attached to the rest of the molecule by a single bond. Carbocyclyl is saturated (i.e., containing single C-C bonds only) or unsaturated (i.e., containing one or more double bonds or triple bonds). A fully saturated carbocyclyl radical is also referred to as "cycloalkyl." Examples of monocyclic cycloalkyls include, e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. An unsaturated carbocyclyl is also referred to as "cycloalkenyl." Examples of monocyclic cycloalkenyls include, e.g., cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl. Polycyclic carbocyclyl radicals include, for example, adamantyl, norbornyl (i.e., bicyclo[2.2.1]heptanyl), norbornenyl, decalinyl, 7,7-dimethyl-bicyclo[2.2.1]heptanyl, and the like. Unless otherwise stated specifically in the specification, the term "carbocyclyl" is meant to include carbocyclyl radicals that are optionally substituted by one or more substituents independently selected from optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, halo, oxo, thioxo, cyano, nitro, -R ^b -OR ^a , -R ^b -OC(O)-R ^a , -R ^b -OC(O)-OR ^a , -R ^b -OC(O)-N(R ^a ) ₂ , -R ^b - N(R ^a )2, -R ^b -C(O)R ^a , -R ^b -C(O)OR ^a , -R ^b -C(O)N(R ^a )2, -R ^b -O-R ^c -C(O)N(R ^a )2, -R ^b -N(R ^a )C(O)OR ^a , -R ^b -N(R ^a )C(O)R ^a , -R ^b -N(R ^a )S(O)tR ^a (where t is 1 or 2), -R ^b -S(O)tR ^a (where t is 1 or 2), -R ^b - S(O) _t OR ^a (where t is 1 or 2) and -R ^b -S(O) _t N(R ^a ) ₂ (where t is 1 or 2), where each R ^a is independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), fluoroalkyl, cycloalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), cycloalkylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, or WSGR Docket No.62619-716.601 trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), each R ^b is independently a direct bond or a straight or branched alkylene or alkenylene chain, and R ^c is a straight or branched alkylene or alkenylene chain, and where each of the R ^a , R ^b , or R ^c substituents is unsubstituted unless otherwise indicated. [0033] "Carbocyclylalkyl" refers to a radical of the formula –R ^c -carbocyclyl where R ^c is an alkylene chain as defined above. The alkylene chain and the carbocyclyl radical is optionally substituted as defined above. [0034] "Carbocyclylalkynyl" refers to a radical of the formula –R ^c -carbocyclyl where R ^c is an alkynylene chain as defined above. The alkynylene chain and the carbocyclyl radical is optionally substituted as defined above. [0035] "Carbocyclylalkoxy" refers to a radical bonded through an oxygen atom of the formula – O-R ^c -carbocyclyl where R ^c is an alkylene chain as defined above. The alkylene chain and the carbocyclyl radical is optionally substituted as defined above. [0036] "Halo" or "halogen" refers to bromo, chloro, fluoro or iodo substituents. [0037] "Fluoroalkyl" refers to an alkyl radical, as defined above, that is substituted by one or more fluoro radicals, as defined above, for example, trifluoromethyl, difluoromethyl, fluoromethyl, 2,2,2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl, and the like. In some embodiments, the alkyl part of the fluoroalkyl radical is optionally substituted as defined above for an alkyl group. [0038] "Heterocyclyl" refers to a stable 3- to 18-membered non-aromatic ring radical that comprises two to twelve carbon atoms and from one to six heteroatoms selected from nitrogen, oxygen and sulfur. Unless stated otherwise specifically in the specification, the heterocyclyl radical is a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which optionally includes fused or bridged ring systems. The heteroatoms in the heterocyclyl radical are optionally oxidized. One or more nitrogen atoms, if present, are optionally quaternized. The heterocyclyl radical is partially or fully saturated. The heterocyclyl is attached to the rest of the molecule through any atom of the ring(s). Examples of such heterocyclyl radicals include, but are not limited to, dioxolanyl, thienyl[1,3]dithianyl, decahydroisoquinolyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, trithianyl, tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpholinyl, and 1,1-dioxo-thiomorpholinyl. Unless stated otherwise specifically in the specification, the term WSGR Docket No.62619-716.601 "heterocyclyl" is meant to include heterocyclyl radicals as defined above that are optionally substituted by one or more substituents selected from optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, halo, fluoroalkyl, oxo, thioxo, cyano, nitro, - R ^b -OR ^a , -R ^b -OC(O)-R ^a , -R ^b -OC(O)-OR ^a , -R ^b -OC(O)-N(R ^a )2, -R ^b -N(R ^a )2, -R ^b -C(O)R ^a , -R ^b - C(O)OR ^a , -R ^b -C(O)N(R ^a ) ₂ , -R ^b -O-R ^c -C(O)N(R ^a ) ₂ , -R ^b -N(R ^a )C(O)OR ^a , -R ^b -N(R ^a )C(O)R ^a , -R ^b - N(R ^a )S(O)tR ^a (where t is 1 or 2), -R ^b -S(O)tR ^a (where t is 1 or 2), -R ^b -S(O)tOR ^a (where t is 1 or 2) and -R ^b -S(O)tN(R ^a )2 (where t is 1 or 2), where each R ^a is independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), fluoroalkyl, cycloalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), cycloalkylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), each R ^b is independently a direct bond or a straight or branched alkylene or alkenylene chain, and R ^c is a straight or branched alkylene or alkenylene chain, and where each of the R ^a , R ^b , or R ^c substituents is unsubstituted unless otherwise indicated. [0039] "N-heterocyclyl" or “N-attached heterocyclyl” refers to a heterocyclyl radical as defined above containing at least one nitrogen and where the point of attachment of the heterocyclyl radical to the rest of the molecule is through a nitrogen atom in the heterocyclyl radical. An N-heterocyclyl radical is optionally substituted as described above for heterocyclyl radicals. Examples of such N-heterocyclyl radicals include, but are not limited to, 1-morpholinyl, 1- piperidinyl, 1-piperazinyl, 1-pyrrolidinyl, pyrazolidinyl, and imidazolidinyl. [0040] "C-heterocyclyl" or “C-attached heterocyclyl” refers to a heterocyclyl radical as defined above containing at least one heteroatom and where the point of attachment of the heterocyclyl radical to the rest of the molecule is through a carbon atom in the heterocyclyl radical. A C-heterocyclyl radical is optionally substituted as described above for heterocyclyl radicals. Examples of such C-heterocyclyl radicals include, but are not limited to, 2-morpholinyl, 2- or 3- or 4-piperidinyl, 2-piperazinyl, 2- or 3-pyrrolidinyl, and the like. [0041] "Heterocyclylalkyl" refers to a radical of the formula –R ^c -heterocyclyl where R ^c is an alkylene chain as defined above. If the heterocyclyl is a nitrogen-containing heterocyclyl, the heterocyclyl is optionally attached to the alkyl radical at the nitrogen atom. The alkylene chain of the heterocyclylalkyl radical is optionally substituted as defined above for an alkylene chain. WSGR Docket No.62619-716.601 The heterocyclyl part of the heterocyclylalkyl radical is optionally substituted as defined above for a heterocyclyl group. [0042] "Heterocyclylalkoxy" refers to a radical bonded through an oxygen atom of the formula –O-R ^c -heterocyclyl where R ^c is an alkylene chain as defined above. If the heterocyclyl is a nitrogen-containing heterocyclyl, the heterocyclyl is optionally attached to the alkyl radical at the nitrogen atom. The alkylene chain of the heterocyclylalkoxy radical is optionally substituted as defined above for an alkylene chain. The heterocyclyl part of the heterocyclylalkoxy radical is optionally substituted as defined above for a heterocyclyl group. [0043] "Heteroaryl" refers to a radical derived from a 3 to 18 membered aromatic ring radical that comprises two to seventeen carbon atoms and from one to six heteroatoms selected from nitrogen, oxygen, and sulfur. As used herein, the heteroaryl radical is a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, wherein at least one of the rings in the ring system is fully unsaturated, i.e., it contains a cyclic, delocalized (4n+2) p–electron system in accordance with the Hückel theory. Heteroaryl includes fused or bridged ring systems. The heteroatom(s) in the heteroaryl radical is optionally oxidized. One or more nitrogen atoms, if present, are optionally quaternized. The heteroaryl is attached to the rest of the molecule through any atom of the ring(s). Examples of heteroaryls include, but are not limited to, azepinyl, acridinyl, benzimidazolyl, benzindolyl, 1,3benzodioxolyl, benzofuranyl, benzooxazolyl, benzo[d]thiazolyl, benzothiadiazolyl, benzo[b][1,4]dioxepinyl, benzo[b][1,4]oxazinyl, 1,4benzodioxanyl, benzonaphthofuranyl, benzoxazolyl, benzodioxolyl, benzodioxinyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, benzothienyl (benzothiophenyl), benzothieno[3,2d]pyrimidinyl, benzotriazolyl, benzo[4,6]imidazo[1,2a]pyridinyl, carbazolyl, cinnolinyl, cyclopenta[d]pyrimidinyl, 6,7dihydro5Hcyclopenta[4,5]thieno[2,3d]pyrimidinyl, 5,6dihydrobenzo[h]quinazolinyl, 5,6dihydrobenzo[h]cinnolinyl, 6,7-dihydro-5H- benzo[6,7]cyclohepta[1,2-c]pyridazinyl, dibenzofuranyl, dibenzothiophenyl, furanyl, furanonyl, furo[3,2c]pyridinyl, 5,6,7,8,9,10hexahydrocycloocta[d]pyrimidinyl, 5,6,7,8,9,10hexahydrocycloocta[d]pyridazinyl, 5,6,7,8,9,10hexahydrocycloocta[d]pyridinyl, isothiazolyl, imidazolyl, indazolyl, indolyl, indazolyl, isoindolyl, indolinyl, isoindolinyl, isoquinolyl, indolizinyl, isoxazolyl, 5,8methano5,6,7,8tetrahydroquinazolinyl, naphthyridinyl, 1,6naphthyridinonyl, oxadiazolyl, 2oxoazepinyl, oxazolyl, oxiranyl, 5,6,6a,7,8,9,10,10aoctahydrobenzo[h]quinazolinyl, 1phenyl1Hpyrrolyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyrazolo[3,4d]pyrimidinyl, pyridinyl, pyrido[3,2d]pyrimidinyl, pyrido[3,4d]pyrimidinyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrrolyl, quinazolinyl, quinoxalinyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, 5,6,7,8tetrahydroquinazolinyl, WSGR Docket No.62619-716.601 5,6,7,8tetrahydrobenzo[4,5]thieno[2,3d]pyrimidinyl, 6,7,8,9tetrahydro5Hcyclohepta[4,5]thieno[2,3d]pyrimidinyl, 5,6,7,8tetrahydropyrido[4,5c]pyridazinyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, triazinyl, thieno[2,3d]pyrimidinyl, thieno[3,2d]pyrimidinyl, thieno[2,3c]pridinyl, and thiophenyl (i.e. thienyl). Unless stated otherwise specifically in the specification, the term "heteroaryl" is meant to include heteroaryl radicals as defined above which are optionally substituted by one or more substituents selected from optionally substituted alkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, optionally substituted alkenyl, optionally substituted alkynyl, halo, optionally substituted fluoroalkyl, optionally substituted haloalkenyl, optionally substituted haloalkynyl, oxo, thioxo, cyano, nitro, -R ^b -OR ^a , -R ^b -OC(O)-R ^a , -R ^b -OC(O)-OR ^a , - R ^b -OC(O)-N(R ^a ) ₂ , -R ^b -N(R ^a ) ₂ , -R ^b -C(O)R ^a , -R ^b -C(O)OR ^a , -R ^b -C(O)N(R ^a ) ₂ , -R ^b -O-R ^c - C(O)N(R ^a )2, -R ^b -N(R ^a )C(O)OR ^a , -R ^b -N(R ^a )C(O)R ^a , -R ^b -N(R ^a )S(O)tR ^a (where t is 1 or 2), -R ^b - S(O)tR ^a (where t is 1 or 2), -R ^b -S(O)tOR ^a (where t is 1 or 2) and -R ^b -S(O)tN(R ^a )2 (where t is 1 or 2), where each R ^a is independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), fluoroalkyl, cycloalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), cycloalkylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), each R ^b is independently a direct bond or a straight or branched alkylene or alkenylene chain, and R ^c is a straight or branched alkylene or alkenylene chain, and where each of the R ^a , R ^b , or R ^c substituents is unsubstituted unless otherwise indicated. [0044] "N-heteroaryl" refers to a heteroaryl radical as defined above containing at least one nitrogen and where the point of attachment of the heteroaryl radical to the rest of the molecule is through a nitrogen atom in the heteroaryl radical. An N-heteroaryl radical is optionally substituted as described above for heteroaryl radicals. [0045] "C-heteroaryl" refers to a heteroaryl radical as defined above and where the point of attachment of the heteroaryl radical to the rest of the molecule is through a carbon atom in the heteroaryl radical. A C-heteroaryl radical is optionally substituted as described above for heteroaryl radicals. [0046] "Heteroarylalkyl" refers to a radical of the formula –R ^c heteroaryl, where R ^c is an alkylene chain as defined above. If the heteroaryl is a nitrogen-containing heteroaryl, the WSGR Docket No.62619-716.601 heteroaryl is optionally attached to the alkyl radical at the nitrogen atom. The alkylene chain of the heteroarylalkyl radical is optionally substituted as defined above for an alkylene chain. The heteroaryl part of the heteroarylalkyl radical is optionally substituted as defined above for a heteroaryl group. [0047] "Heteroarylalkoxy" refers to a radical bonded through an oxygen atom of the formula – O-R ^c heteroaryl, where R ^c is an alkylene chain as defined above. If the heteroaryl is a nitrogen- containing heteroaryl, the heteroaryl is optionally attached to the alkyl radical at the nitrogen atom. The alkylene chain of the heteroarylalkoxy radical is optionally substituted as defined above for an alkylene chain. The heteroaryl part of the heteroarylalkoxy radical is optionally substituted as defined above for a heteroaryl group. [0048] The compounds disclosed herein, in some embodiments, contain one or more asymmetric centers and thus give rise to enantiomers, diastereomers, and other stereoisomeric forms that are defined, in terms of absolute stereochemistry, as (R)- or (S)-. Unless stated otherwise, it is intended that all stereoisomeric forms of the compounds disclosed herein are contemplated by this disclosure. When the compounds described herein contain alkene double bonds, and unless specified otherwise, it is intended that this disclosure includes both E and Z geometric isomers (e.g., cis or trans.) Likewise, all possible isomers, as well as their racemic and optically pure forms, and all tautomeric forms are also intended to be included. The term “geometric isomer” refers to E or Z geometric isomers (e.g., cis or trans) of an alkene double bond. The term “positional isomer” refers to structural isomers around a central ring, such as ortho-, meta-, and para- isomers around a benzene ring. [0049] As used herein, “carboxylic acid bioisostere” refers to a functional group or moiety that exhibits similar physical, biological and/or chemical properties as a carboxylic acid moiety. Examples of carboxylic acid bioisosteres include, but are not limited to, [0050] A "tautomer" refers to a molecule wherein a proton shift from one atom of a molecule to another atom of the same molecule is possible. The compounds presented herein, in certain embodiments, exist as tautomers. In circumstances where tautomerization is possible, a chemical equilibrium of the tautomers will exist. The exact ratio of the tautomers depends on several WSGR Docket No.62619-716.601 factors, including physical state, temperature, solvent, and pH. Some examples of tautomeric equilibrium include: [0051] The compounds disclosed herein, in some embodiments, are used in different enriched isotopic forms, e.g., enriched in the content of ² H, ³ H, ¹¹ C, ¹³ C and/or ¹⁴ C. In one particular embodiment, the compound is deuterated in at least one position. Such deuterated forms can be made by the procedure described in U.S. Patent Nos.5,846,514 and 6,334,997. As described in U.S. Patent Nos.5,846,514 and 6,334,997, deuteration can improve the metabolic stability and or efficacy, thus increasing the duration of action of drugs. [0052] Unless otherwise stated, structures depicted herein are intended to include compounds which differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structures except for the replacement of a hydrogen by a deuterium or tritium, or the replacement of a carbon by ¹³ C- or ¹⁴ C-enriched carbon are within the scope of the present disclosure. [0053] The compounds of the present disclosure optionally contain unnatural proportions of atomic isotopes at one or more atoms that constitute such compounds. For example, the compounds may be labeled with isotopes, such as for example, deuterium ( ² H), tritium ( ³ H), iodine-125 ( ¹²⁵ I) or carbon-14 ( ¹⁴ C). Isotopic substitution with ² H, ¹¹ C, ¹³ C, ¹⁴ C, ¹⁵ C, ¹² N, ¹³ N, ¹⁵ N, ¹⁶ N, ¹⁶ O, ¹⁷ O, ¹⁴ F, ¹⁵ F, ¹⁶ F, ¹⁷ F, ¹⁸ F, ³³ S, ³⁴ S, ³⁵ S, ³⁶ S, ³⁵ Cl, ³⁷ Cl, ⁷⁹ Br, ⁸¹ Br, ¹²⁵ I are all contemplated. In some embodiments, isotopic substitution with ¹⁸ F is contemplated. All isotopic variations of the compounds of the present invention, whether radioactive or not, are encompassed within the scope of the present invention. [0054] In certain embodiments, the compounds disclosed herein have some or all of the ¹ H atoms replaced with ² H atoms. The methods of synthesis for deuterium-containing compounds WSGR Docket No.62619-716.601 are known in the art and include, by way of non-limiting example only, the following synthetic methods. [0055] Deuterium substituted compounds are synthesized using various methods such as described in: Dean, Dennis C.; Editor. Recent Advances in the Synthesis and Applications of Radiolabeled Compounds for Drug Discovery and Development. [Curr., Pharm. Des., 2000; 6(10)] 2000, 110 pp; George W.; Varma, Rajender S. The Synthesis of Radiolabeled Compounds via Organometallic Intermediates, Tetrahedron, 1989, 45(21), 6601-21; and Evans, E. Anthony. Synthesis of radiolabeled compounds, J. Radioanal. Chem., 1981, 64(1-2), 9-32. [0056] Deuterated starting materials are readily available and are subjected to the synthetic methods described herein to provide for the synthesis of deuterium-containing compounds. Large numbers of deuterium-containing reagents and building blocks are available commercially from chemical vendors, such as Aldrich Chemical Co. [0057] Deuterium-transfer reagents suitable for use in nucleophilic substitution reactions, such as iodomethane-d ₃ (CD ₃ I), are readily available and may be employed to transfer a deuterium- substituted carbon atom under nucleophilic substitution reaction conditions to the reaction substrate. The use of CD3I is illustrated, by way of example only, in the reaction schemes below. [0058] Deuterium-transfer reagents, such as lithium aluminum deuteride (LiAlD4), are employed to transfer deuterium under reducing conditions to the reaction substrate. The use of LiAlD4 is illustrated, by way of example only, in the reaction schemes below. [0059] Deuterium gas and palladium catalyst are employed to reduce unsaturated carbon-carbon linkages and to perform a reductive substitution of aryl carbon-halogen bonds as illustrated, by way of example only, in the reaction schemes below. WSGR Docket No.62619-716.601 [0060] In one embodiment, the compounds disclosed herein contain one deuterium atom. In another embodiment, the compounds disclosed herein contain two deuterium atoms. In another embodiment, the compounds disclosed herein contain three deuterium atoms. In another embodiment, the compounds disclosed herein contain four deuterium atoms. In another embodiment, the compounds disclosed herein contain five deuterium atoms. In another embodiment, the compounds disclosed herein contain six deuterium atoms. In another embodiment, the compounds disclosed herein contain more than six deuterium atoms. In another embodiment, the compound disclosed herein is fully substituted with deuterium atoms and contains no non-exchangeable ¹ H hydrogen atoms. In one embodiment, the level of deuterium incorporation is determined by synthetic methods in which a deuterated synthetic building block is used as a starting material. [0061] "Pharmaceutically acceptable salt" includes both acid and base addition salts. A pharmaceutically acceptable salt of any one of the AKT1 inhibitory compounds described herein is intended to encompass any and all pharmaceutically suitable salt forms. Preferred pharmaceutically acceptable salts of the compounds described herein are pharmaceutically acceptable acid addition salts and pharmaceutically acceptable base addition salts. [0062] "Pharmaceutically acceptable acid addition salt" refers to those salts which retain the biological effectiveness and properties of the free bases, which are not biologically or otherwise undesirable, and which are formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, hydroiodic acid, hydrofluoric acid, phosphorous acid, and the like. Also included are salts that are formed with organic acids such as aliphatic mono- and dicarboxylic acids, phenyl-substituted alkanoic acids, hydroxy alkanoic acids, alkanedioic acids, aromatic acids, aliphatic and. aromatic sulfonic acids, etc. and include, for example, acetic acid, trifluoroacetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, and the like. Exemplary salts thus include sulfates, pyrosulfates, bisulfates, sulfites, bisulfites, nitrates, phosphates, monohydrogenphosphates, dihydrogenphosphates, metaphosphates, pyrophosphates, chlorides, bromides, iodides, acetates, trifluoroacetates, propionates, caprylates, isobutyrates, oxalates, malonates, succinate suberates, sebacates, fumarates, maleates, mandelates, WSGR Docket No.62619-716.601 benzoates, chlorobenzoates, methylbenzoates, dinitrobenzoates, phthalates, benzenesulfonates, toluenesulfonates, phenylacetates, citrates, lactates, malates, tartrates, methanesulfonates, and the like. Also contemplated are salts of amino acids, such as arginates, gluconates, and galacturonates (see, for example, Berge S.M. et al., "Pharmaceutical Salts," Journal of Pharmaceutical Science, 66:1- 19 (1997)). Acid addition salts of basic compounds are, in some embodiments, prepared by contacting the free base forms with a sufficient amount of the desired acid to produce the salt according to methods and techniques with which a skilled artisan is familiar. [0063] "Pharmaceutically acceptable base addition salt" refers to those salts that retain the biological effectiveness and properties of the free acids, which are not biologically or otherwise undesirable. These salts are prepared from addition of an inorganic base or an organic base to the free acid. Pharmaceutically acceptable base addition salts are, in some embodiments, formed with metals or amines, such as alkali and alkaline earth metals or organic amines. Salts derived from inorganic bases include, but are not limited to, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum salts and the like. Salts derived from organic bases include, but are not limited to, salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins, for example, isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, diethanolamine, 2-dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, N,N- dibenzylethylenediamine, chloroprocaine, hydrabamine, choline, betaine, ethylenediamine, ethylenedianiline, N-methylglucamine, glucosamine, methylglucamine, theobromine, purines, piperazine, piperidine, N-ethylpiperidine, polyamine resins and the like. See Berge et al., supra. [0064] "Pharmaceutically acceptable solvate" refers to a composition of matter that is the solvent addition form. In some embodiments, solvates contain either stoichiometric or non- stoichiometric amounts of a solvent, and are formed during the process of making with pharmaceutically acceptable solvents such as water, ethanol, and the like. Hydrates are formed when the solvent is water, or alcoholates are formed when the solvent is alcohol. Solvates of compounds described herein are conveniently prepared or formed during the processes described herein. The compounds provided herein exist in either unsolvated or solvated forms. [0065] The term “subject” or “patient” encompasses mammals. Examples of mammals include, but are not limited to, any member of the mammalian class: humans, non-human primates such as chimpanzees, and other apes and monkey species; farm animals such as cattle, horses, sheep, goats, swine; domestic animals such as rabbits, dogs, and cats; laboratory animals including rodents, such as rats, mice and guinea pigs, and the like. In one aspect, the mammal is a human. WSGR Docket No.62619-716.601 [0066] As used herein, “treatment” or “treating,” or “palliating” or “ameliorating” are used interchangeably. These terms refer to an approach for obtaining beneficial or desired results including but not limited to therapeutic benefit and/or a prophylactic benefit. By “therapeutic benefit” is meant eradication or amelioration of the underlying disorder being treated. Also, a therapeutic benefit is achieved with the eradication or amelioration of one or more of the physiological symptoms associated with the underlying disorder such that an improvement is observed in the patient, notwithstanding that the patient is still afflicted with the underlying disorder. For prophylactic benefit, the compositions are, in some embodiments, administered to a patient at risk of developing a particular disease, or to a patient reporting one or more of the physiological symptoms of a disease, even though a diagnosis of this disease has not been made. AKT1 Protein and Function [0067] AKT, also known as protein kinase B (PKB), is a serine/threonine protein kinase with three isoforms, AKT1, AKT2, and AKT3. While the isoforms are encoded by different genes, they are highly homologous at the protein level and share a conserved domain structure comprising an N-terminal pleckstrin homology (PH) domain, a kinase domain, and a C-terminal regulatory domain comprising a hydrophobic moiety, which includes the regulatory serine residue (Nitulescu, G. M. et al., Int J Oncol., 2018; 53(6): 2319-2331). [0068] AKT proteins play a crucial role in major cellular functions including cell cycle progression, cell size, regulation of glucose metabolism, transcription, protein synthesis, genome stability, and neovascularization. AKT proteins can block apoptosis by inactivation of pro- apoptotic proteins, and mediate cellular growth factors, promoting cell survival. AKT is a major nucleus of a cell. [0069] AKT1 is ubiquitously expressed, whereas AKT2 is primarily expressed in insulin- responsive tissues, and AKT3 is primarily expressed in brain and testes. A shared phosphorylation site of AKT in the catalytic domain corresponds to a threonine residue; specifically, Thr308 in AKT1, Thr309 in AKT2, and Thr305 in AKT3. A shared phosphorylation site in the C-terminus of the protein cis a serine residue; specifically, Ser473 in AKT1, Ser474 in AKT2, and Ser472 in AKT3. [0070] AKT is a key downstream mediator of the phosphoinositide-3-kinase (PI3K) signaling are activated by extracellular ligands binding to a transmembrane glycoprotein with enzymatic compound receptors (GPCRs) and by RAS family of GTPases. WSGR Docket No.62619-716.601 [0071] The AKT cascade can be activated by RTKs and G-protein-compound receptors (GPCRs), along with other signals including integrins, B cell receptors, T cell receptors, and cytokine receptors. AKT1 Mechanism [0072] AKT is activated by a second phosphorylation at the regulatory serine residue, Ser473. Known phosphorylating agents of AKT at Ser473 include, but are not limited to PDK-1, integrin-linked kinase (ILK), members of the PI3K-related kinase (PIKK) family, and mammalian target of rapamycin (mTOR) (Nitulescu, G. M. et al., Int J Oncol., 2018; 53(6): 2319-2331). [0073] mTOR is a key component in the AKT signaling pathway, which is a downstream member of AKT and an important regulator for cell metabolism and growth. mTOR is also an activator which can directly phosphorylate AKT’s regulatory serine residue, Ser473. mTOR forms a complex with rapamycin-insensitive companion of mTOR (RICTOR) (and other proteins) to form mTOR complex 2 (mTORC2), which can directly phosphorylate AKT Ser473. AKT can affect cell survival and growth because it can influence the tuberous sclerosis complex (TSC) 1/2 along the mTORC signaling pathway and inhibit pro-apoptotic proteins or signals. [0074] AKT is known as a survival kinase and mediates cell survival and proliferation by inhibiting pathways including, but not limited to Bcl2 and MDM2, which promotes apoptosis. Studies have shown that the AKT signaling cascade have frequent malfunctions in various cancers, and may be associated with tumor aggressiveness (Nitulescu, G. M. et al., Int J Oncol., 2018; 53(6): 2319-2331). Malfunctions of AKT typically lead to enhanced proliferation, growth, survival, and resistance to apoptosis (Alwhaibi, A. et al., Pharmacol Res., 2019, 145: 104270). Malfunction and mis-regulation of AKT may lead to cancers such as but not limited to breast cancer, gastric carcinoma, glioblastoma, gliosarcomas, head and neck squamous cell carcinoma, ovarian cancer, pancreatic cancer, and prostate cancer. [0075] Additionally, AKT1 has been found to be involved in invasion and migration of cancerous cells (Alwhaibi, A. et al., Pharmacol Res., 2019, 145: 104270). Researchers found that silencing the AKT1 isoform can abrogate specific types of cancer cell migration. However, there have been other studies which have demonstrated that activated AKT1 resulted in less metastatic propensity for lung metastatic lesion cells and breast cancer cells. AKT1 has also been identified as a key protein involved in angiogenesis, lung cancer, and tumorigenesis. [0076] Furthermore, overexpression of AKT has been correlated to resistance to chemotherapeutic agents such as cisplatin, methotrexate, and paclitaxel. Thus, there remains a need to find AKT inhibitors given its role in cell survival and cancer proliferation. WSGR Docket No.62619-716.601 [0077] Recently, it has been found that the AKT1 gene mutation E17K can affect cell growth, proliferation, survival, and migration of breast cancer cells, colorectal cancer cells, and ovarian cancer cells (Chen, Y. et al., Front Cell Dev Biol., 2020; 8: 573599). These mutations in the PH structural domain increase the binding of AKT1 to Phosphatidylinositol-3,4,5-triphosphate (PIP3) lipid ligand, which accelerates transfer of AKT from the cytoplasm to the cell membrane through formation of hydrogen bonds. Transfer of AKT into the cell membrane allows it to be further phosphorylated. Once fully activated, AKT can return to the cytoplasm, or go to the nucleus or other intracellular sites, and phosphorylate other substrate proteins to regulate cell function. [0078] The E17K mutation enhances migration of breast cancer cells, and also enhances resistance to chemotherapeutic drugs. However, the E17K mutation can also selectively destroy chemo-resistant tumor-promoting AKT1 quiescent cancer cells, suggesting that the AKT1(E17K) mutation is crucial in the oncogenic/anti-tumor mechanism. [0079] A major pathway that activates PI3K-AKT signaling pathway is somatic cell mutations, with the E17K mutation being the highest frequency of AKT1 mutations. It is nearly exclusively present in AKT1. The AKT1(E17K) is a recurrent somatic cell mutation predominantly in breast cancer, ovarian cancer, meningioma, and Proteus syndrome. [0080] AKT1(E17K) mutations mediate the PI3K-AKT signaling cascade by expanding PIP lipid specificity, which causes conformational changes. This also enhances subcellular localization to accelerate localization of the PH structural domain to the plasma membrane. The E17K mutation increases PIP3 binding specificity by 7-fold and phosphatidylinositol-(4,5)- bisphosphate (PIP2) by 100-fold. [0081] The AKT1(E17K) mutation also causes rapid conformational changes in the AKT1 PH structural domain. The conformational changes to this domain result in a 4.5-fold increase in its membrane localization, which can result in excessive phosphorylation. The AKT1(E17K) mutation can also result in enhanced subcellular localization by increasing the transient expression. [0082] Given the conformational and signaling effects of the AKT1(E17K) mutation, this target may be useful for targeted treatment of cancers. Prior Art AKT1 Inhibitors [0083] Most AKT inhibitors targeting the ATP binding site are non-selective against the three isoforms, as well as having poor to no selectivity against other structurally similar kinases. Thus, there remains a need to develop new and novel AKT inhibitors. These ATP targeting inhibitors are classified as aminofurazans, azepane derivatives, isoquinoline-5-sulfonamides, WSGR Docket No.62619-716.601 phenylpyrazole derivatives, thiophene carboxamide derivatives, and thiazole carboxamide derivatives. [0084] There are also ATP non-competitive AKT inhibitors which are allosteric modulators which have greater specificity than the ATP targeting inhibitors. Many of these allosteric modulator inhibitors are classified as purine derivatives, thiourea derivatives, alkylphospholipids, sulfonamides, 2,3-diphenylquinoxaline analogs, and indole-3-carbinol derivatives. Novel AKT1 Inhibitory Compounds [0085] In one aspect, provided herein is an AKT1 inhibitory compound. [0086] One embodiment provides a compound having the structure of Formula (I), or a pharmaceutically acceptable salt or solvate thereof: wherein: Z ¹ is N, C-H, or C-R ³ ; Z ² is N, C-H, or C-R ⁴ ; X is -C(O)-, or -S(O) ₂ -; R ¹ is selected from hydrogen, halogen, -CN, optionally substituted C1-C6 alkyl, optionally substituted aryl, or optionally substituted heteroaryl; R ² is selected from hydrogen, halogen, -CN, optionally substituted C1-C6 alkyl, optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted C3-C10 carbocyclyl, or optionally substituted heteroaryl; R ³ is selected from halogen, -CN, optionally substituted C1-C6 alkyl, or optionally substituted aryl; R ⁴ is selected from halogen, -CN, optionally substituted C1-C6 alkyl, or optionally substituted aryl; R ⁵ and R ⁶ are each independently hydrogen, deuterium, halogen, -OH, or optionally substituted C1-C6 alkyl; or R ⁵ and R ⁶ together form an oxo; or R ⁵ and R ⁶ join together to form a carbocycle or heterocycle; L is selected from -N(R ⁷ )-, or a divalent radical selected from: WSGR Docket No.62619-716.601 wherein the asterisk (*) indicates the bond to the X group; WSGR Docket No.62619-716.601 a is 0, 1, 2, 3, or 4; b is 0, 1, 2, 3, or 4; c is 1, 2, 3, or 4; d is 1, 2, 3, or 4; e is 0, 1, 2, 3, or 4; f is 0, 1, 2, 3, or 4; provided that e and f are not both 0; g is 0, 1, 2, 3, or 4; provided that e and g are not both 0; h is 0, 1, 2, 3, or 4; provided that g and h are not both 0; and provided that f and h are not both 0; m is 0, 1, or 2; n is 1, 2, or 3 R ⁷ is hydrogen, optionally substituted C1-C6 alkyl, optionally substituted C3-C7 cycloalkyl, optionally substituted heterocyclyl, or R ⁷ and V join together to form a carbocycle or heterocycle; V is selected from: each R ⁸ , R ⁹ , R ¹⁰ , and R ¹¹ is independently selected from hydrogen, F, CN, optionally substituted C1-C6 alkyl, optionally substituted aryl, and optionally substituted alkoxy. [0087] One embodiment provides a compound having the structure of Formula (Ia), or a pharmaceutically acceptable salt or solvate thereof: wherein: Z ¹ is N, C-H, or C-R ³ ; Z ² is N, C-H, or C-R ⁴ ; R ¹ is selected from hydrogen, halogen, -CN, optionally substituted C1-C6 alkyl, optionally substituted aryl, or optionally substituted heteroaryl; WSGR Docket No.62619-716.601 R ² is selected from hydrogen, halogen, -CN, optionally substituted C1-C6 alkyl, optionally substituted aryl, or optionally substituted heteroaryl; R ³ is selected from halogen, -CN, optionally substituted C1-C6 alkyl, or optionally substituted aryl; R ⁴ is selected from halogen, -CN, optionally substituted C1-C6 alkyl, or optionally substituted aryl; R ⁵ and R ⁶ are each independently hydrogen, deuterium, halogen, -OH, or optionally substituted C1-C6 alkyl; or R ⁵ and R ⁶ together form an oxo; or R ⁵ and R ⁶ join together to form a carbocycle or heterocycle; L is selected from -N(R ⁷ )-, or a divalent radical selected from: WSGR Docket No.62619-716.601 wherein the asterisk (*) indicates the bond to the X group; a is 0, 1, 2, 3, or 4; b is 0, 1, 2, 3, or 4; c is 1, 2, 3, or 4; d is 1, 2, 3, or 4; e is 0, 1, 2, 3, or 4; f is 0, 1, 2, 3, or 4; provided that e and f are not both 0; g is 0, 1, 2, 3, or 4; provided that e and g are not both 0; h is 0, 1, 2, 3, or 4; provided that g and h are not both 0; and provided that f and h are not both 0; m is 0, 1, or 2; n is 1, 2, or 3 R ⁷ is hydrogen, optionally substituted C1-C6 alkyl, optionally substituted C3-C7 cycloalkyl, or optionally substituted heterocyclyl; X-V is selected from: each R ⁸ , R ⁹ , R ¹⁰ , and R ¹¹ is independently selected from hydrogen, F, CN, optionally substituted C1-C6 alkyl, optionally substituted aryl, and optionally substituted alkoxy. [0088] One embodiment provides an AKT1 inhibitory compound, or a pharmaceutically acceptable salt or solvate thereof, having a structure presented in Table 1. WSGR Docket No.62619-716.601 Table 1 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 Preparation of Compounds [0089] The compounds used in the synthetic chemistry reactions described herein are made according to organic synthesis techniques known to those skilled in this art, starting from commercially available chemicals and/or from compounds described in the chemical literature. "Commercially available chemicals" are obtained from standard commercial sources including Acros Organics (Pittsburgh, PA), Aldrich Chemical (Milwaukee, WI, including Sigma Chemical and Fluka), Apin Chemicals Ltd. (Milton Park, UK), Avocado Research (Lancashire, U.K.), BDH Inc. (Toronto, Canada), Bionet (Cornwall, U.K.), Chemservice Inc. (West Chester, PA), Crescent Chemical Co. (Hauppauge, NY), Eastman Organic Chemicals, Eastman Kodak Company (Rochester, NY), Fisher Scientific Co. (Pittsburgh, PA), Fisons Chemicals (Leicestershire, UK), Frontier Scientific (Logan, UT), ICN Biomedicals, Inc. (Costa Mesa, CA), Key Organics (Cornwall, U.K.), Lancaster Synthesis (Windham, NH), Maybridge Chemical Co. Ltd. (Cornwall, U.K.), Parish Chemical Co. (Orem, UT), Pfaltz & Bauer, Inc. (Waterbury, CN), Polyorganix (Houston, TX), Pierce Chemical Co. (Rockford, IL), Riedel de Haen AG (Hanover, Germany), Spectrum Quality Product, Inc. (New Brunswick, NJ), TCI America (Portland, OR), Trans World Chemicals, Inc. (Rockville, MD), and Wako Chemicals USA, Inc. (Richmond, VA). WSGR Docket No.62619-716.601 [0090] Suitable reference books and treatise that detail the synthesis of reactants useful in the preparation of compounds described herein, or provide references to articles that describe the preparation, include for example, "Synthetic Organic Chemistry", John Wiley & Sons, Inc., New York; S. R. Sandler et al., "Organic Functional Group Preparations," 2nd Ed., Academic Press, New York, 1983; H. O. House, "Modern Synthetic Reactions", 2nd Ed., W. A. Benjamin, Inc. Menlo Park, Calif.1972; T. L. Gilchrist, "Heterocyclic Chemistry", 2nd Ed., John Wiley & Sons, New York, 1992; J. March, "Advanced Organic Chemistry: Reactions, Mechanisms and Structure", 4th Ed., Wiley-Interscience, New York, 1992. Additional suitable reference books and treatise that detail the synthesis of reactants useful in the preparation of compounds described herein, or provide references to articles that describe the preparation, include for example, Fuhrhop, J. and Penzlin G. "Organic Synthesis: Concepts, Methods, Starting Materials", Second, Revised and Enlarged Edition (1994) John Wiley & Sons ISBN: 3-527- 29074-5; Hoffman, R.V. "Organic Chemistry, An Intermediate Text" (1996) Oxford University Press, ISBN 0-19-509618-5; Larock, R. C. "Comprehensive Organic Transformations: A Guide to Functional Group Preparations" 2nd Edition (1999) Wiley-VCH, ISBN: 0-471-19031-4; March, J. "Advanced Organic Chemistry: Reactions, Mechanisms, and Structure" 4th Edition (1992) John Wiley & Sons, ISBN: 0-471-60180-2; Otera, J. (editor) "Modern Carbonyl Chemistry" (2000) Wiley-VCH, ISBN: 3-527-29871-1; Patai, S. "Patai's 1992 Guide to the Chemistry of Functional Groups" (1992) Interscience ISBN: 0-471-93022-9; Solomons, T. W. G. "Organic Chemistry" 7th Edition (2000) John Wiley & Sons, ISBN: 0-471-19095-0; Stowell, J.C., "Intermediate Organic Chemistry" 2nd Edition (1993) Wiley-Interscience, ISBN: 0-471- 57456-2; "Industrial Organic Chemicals: Starting Materials and Intermediates: An Ullmann's Encyclopedia" (1999) John Wiley & Sons, ISBN: 3-527-29645-X, in 8 volumes; "Organic Reactions" (1942-2000) John Wiley & Sons, in over 55 volumes; and "Chemistry of Functional Groups" John Wiley & Sons, in 73 volumes. [0091] Specific and analogous reactants are optionally identified through the indices of known chemicals prepared by the Chemical Abstract Service of the American Chemical Society, which are available in most public and university libraries, as well as through on-line databases (contact the American Chemical Society, Washington, D.C. for more details). Chemicals that are known but not commercially available in catalogs are optionally prepared by custom chemical synthesis houses, where many of the standard chemical supply houses (e.g., those listed above) provide custom synthesis services. A reference useful for the preparation and selection of pharmaceutical salts of the compounds described herein is P. H. Stahl & C. G. Wermuth "Handbook of Pharmaceutical Salts", Verlag Helvetica Chimica Acta, Zurich, 2002. Pharmaceutical Compositions WSGR Docket No.62619-716.601 [0092] In certain embodiments, the AKT1 inhibitory compound described herein is administered as a pure chemical. In other embodiments, the AKT1 inhibitory compound described herein is combined with a pharmaceutically suitable or acceptable carrier (also referred to herein as a pharmaceutically suitable (or acceptable) excipient, physiologically suitable (or acceptable) excipient, or physiologically suitable (or acceptable) carrier) selected on the basis of a chosen route of administration and standard pharmaceutical practice as described, for example, in Remington: The Science and Practice of Pharmacy (Gennaro, 21 ^st Ed. Mack Pub. Co., Easton, PA (2005)). [0093] Provided herein is a pharmaceutical composition comprising at least one AKT1 inhibitory compound as described herein, or a stereoisomer, pharmaceutically acceptable salt, hydrate, or solvate thereof, together with one or more pharmaceutically acceptable carriers. The carrier(s) (or excipient(s)) is acceptable or suitable if the carrier is compatible with the other ingredients of the composition and not deleterious to the recipient (i.e., the subject or the patient) of the composition. [0094] One embodiment provides a pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof. [0095] One embodiment provides a method of preparing a pharmaceutical composition comprising mixing a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable carrier. [0096] One embodiment provides a pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of Formula (Ia), or a pharmaceutically acceptable salt or solvate thereof. [0097] One embodiment provides a method of preparing a pharmaceutical composition comprising mixing a compound of Formula (Ia), or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable carrier. [0098] In certain embodiments, the AKT1 inhibitory compound as described by Formula (I), or a pharmaceutically acceptable salt or solvate thereof, is substantially pure, in that it contains less than about 5%, or less than about 2%, or less than about 1%, or less than about 0.5%, or less than about 0.1%, of other organic small molecules, such as unreacted intermediates or synthesis by-products that are created, for example, in one or more of the steps of a synthesis method. [0099] In certain embodiments, the AKT1 inhibitory compound as described by Formula (Ia), or a pharmaceutically acceptable salt or solvate thereof, is substantially pure, in that it contains less than about 5%, or less than about 2%, or less than about 1%, or less than about 0.5%, or less WSGR Docket No.62619-716.601 than about 0.1%, of other organic small molecules, such as unreacted intermediates or synthesis by-products that are created, for example, in one or more of the steps of a synthesis method. [00100] One embodiment provides a pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of Table 1, or a pharmaceutically acceptable salt or solvate thereof. [00101] One embodiment provides a method of preparing a pharmaceutical composition comprising mixing a compound of Table 1, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable carrier. [00102] In certain embodiments, the AKT1 inhibitory compound as described by Table 1, or a pharmaceutically acceptable salt or solvate thereof, is substantially pure, in that it contains less than about 5%, or less than about 2%, or less than about 1%, or less than about 0.5%, or less than about 0.1%, of other organic small molecules, such as unreacted intermediates or synthesis by-products that are created, for example, in one or more of the steps of a synthesis method. [00103] Suitable oral dosage forms include, for example, tablets, pills, sachets, or capsules of hard or soft gelatin, methylcellulose or of another suitable material easily dissolved in the digestive tract. In some embodiments, suitable nontoxic solid carriers are used which include, for example, pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharin, talcum, cellulose, glucose, sucrose, magnesium carbonate, and the like. (See, e.g., Remington: The Science and Practice of Pharmacy (Gennaro, 21 ^st Ed. Mack Pub. Co., Easton, PA (2005)). [00104] In some embodiments, the AKT1 inhibitory compound as described by Formula (I) or Formula (Ia) or Table 1, or pharmaceutically acceptable salt or solvate thereof, is formulated for administration by injection. In some instances, the injection formulation is an aqueous formulation. In some instances, the injection formulation is a non-aqueous formulation. In some instances, the injection formulation is an oil-based formulation, such as sesame oil, or the like. [00105] The dose of the composition comprising at least one AKT1 inhibitory compound as described herein differs depending upon the subject or patient's (e.g., human) condition. In some embodiments, such factors include general health status, age, and other factors. [00106] Pharmaceutical compositions are administered in a manner appropriate to the disease to be treated (or prevented). An appropriate dose and a suitable duration and frequency of administration will be determined by such factors as the condition of the patient, the type and severity of the patient's disease, the particular form of the active ingredient, and the method of administration. In general, an appropriate dose and treatment regimen provides the composition(s) in an amount sufficient to provide therapeutic and/or prophylactic benefit (e.g., an improved clinical outcome, such as more frequent complete or partial remissions, or longer WSGR Docket No.62619-716.601 disease-free and/or overall survival, or a lessening of symptom severity. Optimal doses are generally determined using experimental models and/or clinical trials. The optimal dose depends upon the body mass, weight, or blood volume of the patient. [00107] Oral doses typically range from about 1.0 mg to about 1000 mg, one to four times, or more, per day. Methods of Treatment [00108] One embodiment provides a compound of Formula (I) or Formula (Ia), or a pharmaceutically acceptable salt or solvate thereof, for use in a method of treatment of the human or animal body. [00109] One embodiment provides a compound of Formula (I) or Formula (Ia), or a pharmaceutically acceptable salt or solvate thereof, for use in a method of treatment of cancer or neoplastic disease. [00110] One embodiment provides a pharmaceutical composition comprising a compound of Formula (I) or Formula (Ia), or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient for use in a method of treatment of cancer or neoplastic disease. [00111] One embodiment provides a use of a compound of Formula (I) or Formula (Ia), or a pharmaceutically acceptable salt or solvate thereof, in the manufacture of a medicament for the treatment of cancer or neoplastic disease. [00112] In some embodiments is provided a method of treating cancer, in a patient in need thereof, comprising administering to the patient a compound of Formula (I) or Formula (Ia), or a pharmaceutically acceptable salt or solvate thereof. In some embodiments is provided a method of treating cancer, in a patient in need thereof, comprising administering to the patient a pharmaceutical composition comprising a compound of Formula (I) or Formula (Ia), or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient. [00113] One embodiment provides a compound of Table 1, or a pharmaceutically acceptable salt or solvate thereof, for use in a method of treatment of the human or animal body. [00114] One embodiment provides a compound of Table 1, or a pharmaceutically acceptable salt or solvate thereof, for use in a method of treatment of cancer or neoplastic disease. [00115] One embodiment provides a pharmaceutical composition comprising a compound of Table 1, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient for use in a method of treatment of cancer or neoplastic disease. [00116] One embodiment provides a use of a compound of Table 1, or a pharmaceutically acceptable salt or solvate thereof, in the manufacture of a medicament for the treatment of cancer or neoplastic disease. WSGR Docket No.62619-716.601 [00117] In some embodiments is provided a method of treating cancer, in a patient in need thereof, comprising administering to the patient a compound of Table 1, or a pharmaceutically acceptable salt or solvate thereof. In some embodiments is provided a method of treating cancer, in a patient in need thereof, comprising administering to the patient a pharmaceutical composition comprising a compound of Table 1, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient. [00118] Provided herein is the method wherein the pharmaceutical composition is administered orally. Provided herein is the method wherein the pharmaceutical composition is administered by injection. [00119] One embodiment provides a method of inhibiting an AKT1 enzyme comprising contacting the AKT1 enzyme with a compound of Formula (I) or Formula (Ia), or Table 1. Another embodiment provides the method of inhibiting an AKT1 enzyme, wherein the AKT1 enzyme is contacted in an in vivo setting. Another embodiment provides the method of inhibiting an AKT1 enzyme, wherein the AKT1 enzyme is contacted in an in vitro setting. [00120] Other embodiments and uses will be apparent to one skilled in the art in light of the present disclosures. The following examples are provided merely as illustrative of various embodiments and shall not be construed to limit the invention in any way. EXAMPLES I. Chemical Synthesis [00121] In some embodiments, the AKT1 inhibitory compounds disclosed herein are synthesized according to the following examples. As used below, and throughout the description of the invention, the following abbreviations, unless otherwise indicated, shall be understood to have the following meanings: ACN acetonitrile ^o C degrees Celsius H chemical shift in parts per million downfield from tetramethylsilane DCM dichloromethane (CH2Cl2) DIAD diisopropyl azodicarboxylate DIEA diisopropylethylamine DMF dimethylformamide DMSO dimethylsulfoxide EA ethyl acetate EtOAc ethyl acetate ESI electrospray ionization WSGR Docket No.62619-716.601 Et ethyl g gram(s) h hour(s) HPLC high performance liquid chromatography Hz hertz J coupling constant (in NMR spectrometry) LCMS liquid chromatography mass spectrometry micro m multiplet (spectral); meter(s); milli M molar M ⁺ parent molecular ion Me methyl MsCl methanesulfonyl chloride MHz megahertz min minute(s) mol mole(s); molecular (as in mol wt) mL milliliter MS mass spectrometry nm nanometer(s) NMR nuclear magnetic resonance pH potential of hydrogen; a measure of the acidity or basicity of an aqueous solution PE petroleum ether RT room temperature s singlet (spectral) t triplet (spectral) SFC Supercritical fluid chromatography T temperature TFA trifluoroacetic acid THF tetrahydrofuran TPP Triphenylphosphine Experimental Procedures [00122] Intermediate 1: 3-(3-(4-(Aminomethyl)phenyl)-5-phenyl-3H-imidazo[4,5-b]pyrid in-2- yl)pyridin-2-amine WSGR Docket No.62619-716.601 [00123] Step 1: tert-Butyl 4-((6-chloro-3-nitropyridin-2-yl)amino)benzylcarbamate [00124] To a solution of 2,6-dichloro-3-nitro-pyridine (2.0 g, 10.4 mmol) and tert-butyl N-[(4- aminophenyl)methyl]carbamate (2.3 g, 10.4 mmol) in DMSO (25 mL) was added DIEA (4.0 g, 31.1 mmol). The mixture was stirred at 80 °C for 12 hr. The reaction mixture was quenched with H ₂ O (50 mL) at 25 °C and extracted with EtOAc (50 mL x 3). The combined organic layers were washed with brine (50 mL x 2), dried over Na2SO4, filtered, and concentrated under reduced pressure to give a crude product. The crude product was purified by flash chromatography on silica gel (Eluent of 0~10% MeOH in CH ₂ Cl ₂ ) to give tert-butyl N-[[4-[(6- chloro-3-nitro-2-pyridyl)amino]phenyl]methyl]carbamate (2.4 g, yield: 44%) as a red solid. MS: m/z = 400.9 [M + Na] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 (d, J = 8.8 Hz, 1H), 7.52 (d, J = 8.4 Hz, 2H), 7.40 (t, J = 6.0 Hz, 1H), 7.25 (d, J = 8.4 Hz, 2H), 6.99 (d, J = 8.8 Hz, 1H), 4.13 (d, J = 6.0 Hz, 2H), 1.40 (s, 9H). [00125] Step 2: tert-Butyl N-[[4-[2-(2-amino-3-pyridyl)-5-chloro-imidazo[4,5-b]pyridin- 3- yl]phenyl]methyl]carbamate [00126] To a solution of tert-butyl N-[[4-[(6-chloro-3-nitro-2- pyridyl)amino]phenyl]methyl]carbamate (2.0 g, 5.3 mmol) in DMSO (30 mL) and MeOH (15 mL) were added 2-aminopyridine-3-carbaldehyde (0.7 g, 5.8 mmol) and Na ₂ S ₂ O ₄ (1.8 g, 10.6 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was quenched with H2O (50 mL) at 25°C, and extracted with EtOAc (100 mL x 3). The combined organic layers were washed with brine (100 mL x 2), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure to give a crude product. The crude product was purified by silica gel flash chromatography (Eluent of 0~10% MeOH in CH2Cl2) to give tert-butyl N-[[4-[2-(2-amino-3- pyridyl)-5-chloro-imidazo[4,5-b]pyridin-3-yl]phenyl]methyl]c arbamate (1.4 g, yield: 51%) as a yellow solid. MS: m/z = 451.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 J = 8.4 Hz, 1H), 7.99 (dd, J = 4.8, 1.6 Hz, 1H), 7.50 - 7.43 (m, 2H), 7.38 (s, 4H), 7.21 (dd, J = WSGR Docket No.62619-716.601 7.6, 1.6 Hz, 1H), 6.91 (br s, 2H), 6.40 (dd, J = 7.6, 4.8 Hz, 1H), 4.22 (d, J = 6.0 Hz, 2H), 1.41 (s, 9H). [00127] Step 3: tert-Butyl N-[[4-[2-(2-amino-3-pyridyl)-5-phenyl-imidazo[4,5-b]pyridin- 3- yl]phenyl]methyl]carbamate [00128] To a solution of tert-butyl N-[[4-[2-(2-amino-3-pyridyl)-5-chloro-imidazo[4,5- b]pyridin-3-yl]phenyl]methyl]carbamate (500 mg, 1.1 mmol) and phenylboronic acid (270 mg, 2.2 mmol,) in 1,4-dioxane (5 mL) and H2O (1 mL) were added Pd(dppf)Cl2 (81.1 mg, 111 µmol) and Cs ₂ CO ₃ (1.1 g, 3.3 mmol). The mixture was was degassed and purged with N ₂ three times and then stirred at 80 °C for 16 hr under N2 atmosphere. After cooling to 20 °C, the reaction was diluted with EtOAc (10 mL), filtered through celite, and extracted with H2O (10 mL x 3). The combined organic layers were washed with brine (15 mL x 3), dried over Na ₂ SO _4, filtered and concentrated under reduced pressure. The crude product was purified by silica gel flash chromatography (Eluent of 10~35% EtOAc in petroleum ether) to give tert-butyl N-[[4-[2-(2- amino-3-pyridyl)-5-phenyl-imidazo[4,5-b]pyridin-3-yl]phenyl] methyl]carbamate (126 mg, yield: 21%) as a brown solid. MS: m/z = 493.2 [M + H] ⁺ . [00129] Step 4: 3-(3-(4-(Aminomethyl)phenyl)-5-phenyl-3H-imidazo[4,5-b]pyrid in-2- yl)pyridin-2-amine [00130] A solution of tert-butyl N-[[4-[2-(2-amino-3-pyridyl)-5-phenyl-imidazo[4,5-b]pyridin- 3-yl]phenyl]methyl]carbamate (126 mg, 256 µmol) in HCl/1,4-dioxane (4 M, 1 mL) was stirred at 25 °C for 2 hr. The solvent was removed under reduced pressure to give a crude product (84 mg, yield: 84%). The crude product was purified by prep-HPLC (column: Welch Xtimate C18 150 * 25mm, 5 µm; mobile phase: [water (HCl) - ACN]; B%: 5% - 35%, 8min) to give the desired product (HCl salt). The product was diluted with aqueous NaHCO ₃ (10 mL) and extracted with DCM (10 mL x 3). The combined organic layers were washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure to give 3-(3-(4- (aminomethyl)phenyl)-5-phenyl-3H-imidazo[4,5-b]pyridin-2-yl) pyridin-2-amine (Intermediate 1, 32.2 mg, yield: 84%) as a light-yellow solid. MS: m/z = 393.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 J = 8.4 Hz, 1H), 8.04 - 7.96 (m, 4H), 7.54 - 7.49 (m, 2H), 7.49 - 7.43 (m, 2H), 7.43 - 7.35 (m, 3H), 7.21 (dd, J = 7.6, 1.6 Hz, 1H), 6.98 (br s, 2H), 6.41 (dd, J = 7.6, 4.8 Hz, 1H), 3.82 (s, 2H). [00131] Intermediate 2: 3-(5-Phenyl-3-(4-(piperazin-1-ylmethyl)phenyl)-3H-imidazo[4, 5- b]pyridin-2-yl)pyridin-2-amine WSGR Docket No.62619-716.601 [00132] Step 1: tert-Butyl 4-(4-((6-chloro-3-nitropyridin-2-yl)amino)benzyl)piperazine- 1- carboxylate [00133] To a solution of 2,6-dichloro-3-nitro-pyridine (5.0 g, 25.9 mmol) in 1,4-dioxane (50 mL) were added DIEA (6.7 g, 51.8 mmol) and tert-butyl 4-[(4-aminophenyl)methyl]piperazine- 1-carboxylate (10.8 g, 25.9 mmol). The mixture was stirred at 60 °C for 12 hr. The reaction mixture was diluted H2O (50 mL) and extracted with EtOAc (100 mL x 3). The combined organic layers were washed with brine (50 mL x 2), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 0~50% EtOAc in petroleum ether) to give tert-butyl 4-[[4-[(6- chloro-3-nitro-2-pyridyl)amino]phenyl]methyl]piperazine-1-ca rboxylate (6.1 g, yield: 53%) as a yellow solid. MS: m/z = 447.9 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d 8.46 (d, J = 8.8 Hz, 1H), 7.61 (d, J = 8.4 Hz, 2H), 7.36 (d, J = 8.4 Hz, 2H), 6.80 (d, J = 8.4 Hz, 1H), 3.52 (s, 2H), 3.48-3.37 (m, 4H), 2.45-2.32 (m, 4H), 1.46 (s, 9H). [00134] Step 2: tert-Butyl 4-[[4-[(3-nitro-6-phenyl-2-pyridyl)amino]phenyl]methyl]piper azine- 1-carboxylate [00135] To a solution of tert-butyl 4-[[4-[(6-chloro-3-nitro-2- pyridyl)amino]phenyl]methyl]piperazine-1-carboxylate (1.0 g, 2.23 mmol) and phenylboronic acid (544 mg, 4.47 mmol) in 1,4-dioxane (10 mL) and H ₂ O (2 mL) were added Pd(dppf)Cl ₂ (327 mg, 0.446 mmol) and K2CO3 (926 mg, 6.7 mmol). The mixture was stirred at 60 °C for 4 hr. The reaction mixture was diluted with H ₂ O (50 mL) and extracted with EtOAc (100 mL x 3). The combined organic layers were washed with brine (50 mL x 2), dried over Na2SO4, filtered, and concentrated under reduced pressure to give a residue. The residue was purified by silica gel flash chromatography (Eluent of 0~50% EtOAc in petroleum ether) to give tert-butyl 4-[[4- [(3-nitro-6-phenyl-2-pyridyl)amino]phenyl]methyl]piperazine- 1-carboxylate (1.0 g, yield: 92%) as a red solid. MS: m/z = 490.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d 8.59 (d, J = 8.8 Hz, 1H), 8.06-8.04 (m, 2H), 7.73 (d, J = 8.4 Hz, 2H), 7.52-7.44 (m, 3H), 7.37 (d, WSGR Docket No.62619-716.601 J = 8.4 Hz, 2H), 7.3 (d, J = 8.4 Hz, 1H), 3.54 (s, 2H), 3.52-3.37 (m, 4H), 2.49-2.37 (m, 4H), 1.46 (s, 9H). [00136] Step 3: tert-Butyl 4-[[4-[2-(2-amino-3-pyridyl)-5-phenyl-imidazo[4,5-b]pyridin- 3- yl]phenyl]methyl]piperazine-1-carboxylate [00137] To a solution of 2-aminopyridine-3-carbaldehyde (269 mg, 2.21 mmol) and tert-butyl 4-[[4-[(3-nitro-6-phenyl-2-pyridyl)amino]phenyl]methyl]piper azine-1-carboxylate (900 mg, 1.84 mmol) in DMSO (10 mL) was added Na2S2O4 (960 mg, 5.52 mmol) at 15 °C. The mixture was stirred at 100 °C for 20 hr. The reaction mixture was diluted with H ₂ O (50 mL) and extracted with DCM (80 mL x 3). The combined organic layers were washed with brine (80 mL x 3), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 0~10% MeOH in CH ₂ Cl ₂ ) to give tert- butyl 4-[[4-[2-(2-amino-3-pyridyl)-5-phenyl-imidazo[4,5-b]pyridin- 3- yl]phenyl]methyl]piperazine-1-carboxylate (600 mg, yield: 58%) as a yellow solid. MS: m/z = 562.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d J = 8.4 Hz, 1H), 8.06 (dd, J = 5.2, 2.0 Hz, 1H), 8.03-8.01 (m, 2H), 7.81 (d, J = 8.4 Hz, 1H), 7.51-7.49 (m, 2H), 7.48-7.35 (m, 5H), 7.10 (dd, J = 9.6, 2.0 Hz, 1H), 6.66 (br s, 2H), 6.36 (dd, J = 8.0, 4.0 Hz, 1H), 3.64 (s, 2H), 3.53-3.42 (m, 4H), 2.55-2.42 (m, 4H), 1.47 (s, 9H). [00138] Step 4: 3-(5-Phenyl-3-(4-(piperazin-1-ylmethyl)phenyl)-3H-imidazo[4, 5-b]pyridin-2- yl)pyridin-2-amine A solution of tert-butyl 4-[[4-[2-(2-amino-3-pyridyl)-5-phenyl-imidazo[4,5- b]pyridin-3-yl]phenyl]methyl]piperazine-1-carboxylate (400 mg, 712 µmol) in HCl/1,4-dioxane (4M, 8 mL) was stirred at 25 °C for 4 hr. The reaction was filtered and concentrated under reduced pressure to give 3-(5-Phenyl-3-(4-(piperazin-1-ylmethyl)phenyl)-3H-imidazo[4, 5- b]pyridin-2-yl)pyridin-2-amine (450 mg, HCl) as a yellow solid, which was used in the next step without further purification. The residue (200 mg) was purified by prep-HPLC (column: Waters xbridge 150*25mm 10 µm; mobile phase: [water(NH4HCO3)-ACN];B%: 19%-49%, 9min) to give 3-(5-phenyl-3-(4-(piperazin-1-ylmethyl)phenyl)-3H-imidazo[4, 5-b]pyridin-2-yl)pyridin-2- amine (Intermediate 2, 49.7 mg) as a yellow solid. MS: m/z = 462.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 J = 8.4 Hz, 1H), 8.04-7.97 (m, 4H), 7.48-7.39 (m, 8H), 7.15 (dd, J = 8.0, 2.0 Hz, 1H), 7.03 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.53 (s, 2H), 2.74- 2.66 (m, 4H), 2.38-2.27 (m, 4H). [00139] Intermediate 3: 3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-5-phenyl-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine WSGR Docket No.62619-716.601 [00140] Step 1: tert-Butyl (1-(4-((6-chloro-3-nitropyridin-2-yl)amino)benzyl)piperidin- 4- yl)carbamate [00141] To a solution of 2,6-dichloro-3-nitro-pyridine (3.0 g, 15.5 mmol) and tert-butyl N-[1- [(4-aminophenyl)methyl]-4-piperidyl]carbamate (4.8 g, 15.6 mmol) in 1,4-dioxane (100 mL) was added DIEA (6.0 g, 46.6 mmol). The mixture was stirred at 50 °C for 12 hr. The reaction mixture was diluted with H2O (50 mL) and extracted with EtOAc (30 mL x 2). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 0~5% MeOH in CH2Cl2) to give tert-butyl N-[1-[[4-[(6-chloro-3-nitro-2- pyridyl)amino]phenyl]methyl]-4-piperidyl]carbamate (4.6 g, yield: 64%) as an orange solid. MS: m/z = 462.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d J = 8.8 Hz, 1H), 7.60 (d, J = 8.8 Hz, 2H), 7.34 (d, J = 8.4 Hz, 2H), 6.79 (d, J = 8.4 Hz, 1H), 4.42 (br s, 1H), 3.48 (s, 2H), 3.48 - 3.39 (m, 1H), 2.82 (br d, J = 10.8 Hz, 2H), 2.10 (br t, J = 10.8 Hz, 2H), 1.92 (br d, J = 10.8 Hz, 2H), 1.50-1.40 (m, 2H).1.44 (s, 9H). [00142] Step 2: tert-Butyl N-[1-[[4-[(3-nitro-6-phenyl-2-pyridyl)amino]phenyl]methyl]-4 - piperidyl]carbamate [00143] A mixture of tert-butyl N-[1-[[4-[(6-chloro-3-nitro-2-pyridyl)amino]phenyl]methyl]-4 - piperidyl]carbamate (1.0 g, 2.20 mmol), phenylboronic acid (528 mg, 4.30 mmol), Pd(dppf)Cl2 (158 mg, 0.216 mmol) and K ₂ CO ₃ (898 mg, 6.50 mmol) in 1,4-dioxane (10 mL) and H ₂ O (2 mL) was degassed and purged with N ₂ three times, and then the mixture was stirred at 100 °C for 12 hr under N2 atmosphere. After cooling to 25 °C, the reaction mixture was diluted with H ₂ O (50 mL) and extracted with DCM (50 mL x 2). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (Eluent of 0~7% MeOH in CH ₂ Cl ₂ ) to give tert-butyl N-[1-[[4-[(3-nitro-6-phenyl-2-pyridyl)amino]phenyl]methyl]-4 - piperidyl]carbamate (1.1 g, yield: 96%) as a yellow solid. MS: m/z = 504.1 [M + H] ⁺ . ¹ H NMR WSGR Docket No.62619-716.601 (400 MHz, Chloroform-d J = 8.8 Hz, 1H), 8.09 - 8.02 (m, 2H), 7.72 (d, J = 8.4 Hz, 2H), 7.51 - 7.47 (m, 3H), 7.36 (d, J = 8.8 Hz, 1H), 7.30 (d, J = 8.8 Hz, 1H), 4.52 - 4.37 (m, 1H), 3.52 (s, 2H), 3.51 - 3.42 (m, 1H), 2.85 (br d, J = 11.2 Hz, 2H), 2.12 (br t, J = 10.8 Hz, 2H), 1.93 (br d, J = 11.0 Hz, 2H), 1.50 - 1.40 (m, 2H).1.44 (s, 9H). [00144] Step 3: tert-Butyl (1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyr idin- 3-yl)benzyl)piperidin-4-yl) carbamate [00145] To a solution of tert-butyl N-[1-[[4-[(3-nitro-6-phenyl-2- pyridyl)amino]phenyl]methyl]-4-piperidyl]carbamate (200 mg, 0.397 mmol), 2-aminopyridine- 3-carbaldehyde (53.4 mg, 0.437 mmol) and Na2S2O4 (207 mg, 1.2 mmol) in DMSO (6 mL). The mixture was stirred at 100 °C for 18 hr. After cooling to 25 °C, the reaction mixture was diluted with DCM (40 mL). The organic layers were washed with H ₂ O (20 mL) and brine (20 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (IEluent of 0~7% MeOH in CH2Cl2) to give tert-butyl N-[1-[[4-[2-(2-amino-3-pyridyl)-5-phenyl-imidazo[4,5-b]pyrid in-3- yl]phenyl]methyl]-4-piperidyl]carbamate (100 mg, yield: 40%) as a yellow solid. MS: m/z = 576.2 [M + H] ⁺ . [00146] Step 4: 3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-5-phenyl-3H-i midazo[4,5- b]pyridin-2-yl)pyridin-2-amine [00147] To a solution of tert-butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)carbamate (200 mg, 0.347 mmol) in HCl in 1,4-dioxane (4 M, 2 mL). The mixture was stirred at 25 °C for 2 hr. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (column: Waters xbridge 150*25mm 10 um; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; B%: 24% - 54%, 8 min) to give 3-(3-(4-((4-aminopiperidin-1-yl)methyl)phenyl)-5-phenyl-3H-i midazo[4,5- b]pyridin-2-yl)pyridin-2-amine (Intermediate 3, 120 mg, yield: 72 %) as a light-yellow solid. MS: m/z = 476.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d J = 8.4 Hz, 1H), 8.05 (dd, J = 5.2, 1.6 Hz, 1H), 8.01 (d, J = 7.2 Hz, 2H), 7.79 (d, J = 8.4 Hz, 1H), 7.50 - 7.35 (m, 7H), 7.09 (dd, J = 7.6, 1.2 Hz, 1H), 6.61 (br s, 2H), 6.35 (dd, J = 7.6, 4.8 Hz, 1H), 3.58 (s, 2H), 2.88 (br d, J = 11.6 Hz, 2H), 2.75 - 2.65 (m, 1H), 2.09 (br t, J = 11.6 Hz, 2H), 1.83 (br d, J = 11.6 Hz, 2H), 1.49 - 1.38 (m, 2H). [00148] Intermediate 4: 3-(3-(4-(Chloromethyl)phenyl)-5-phenyl-3H-imidazo[4,5-b]pyri din-2- yl)pyridin-2-amine WSGR Docket No.62619-716.601 [00149] Step 1: Methyl 4-((6-chloro-3-nitropyridin-2-yl)amino)benzoate [00150] To a solution of methyl 4-aminobenzoate (5 g, 33.1 mmol) in DMSO (50 mL) were added 2,6-dichloro-3-nitro-pyridine (7.66 g, 39.7 mmol) and DIEA (12.82 g, 99.2 mmol). The mixture was stirred at 80 °C for 16 hr. After cooling to 20 °C, the reaction mixture was poured into H ₂ O (100 mL) and extracted with CH ₂ Cl ₂ (100 mL x 3). The combined organic layers were washed with brine (100 mL x 2), dried over anhydrous Na2SO4, filtered, and concentrated to dryness. The crude product was triturated with EtOAc at 25 ^o C for 30 min to give methyl 4-[(6- chloro-3-nitro-2-pyridyl)amino]benzoate (8 g, yield: 51%) as a yellow solid. MS: m/z = 307.8 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 10.25 (s, 1H), 8.57 (d, J = 8.4 Hz, 1H), 7.97 (d, J = 8.8 Hz, 2H), 7.79 (d, J = 8.8 Hz, 2H), 7.12 (d, J = 8.4 Hz, 1H), 3.85 (s, 3H). [00151] Step 2: Methyl 4-((3-nitro-6-phenylpyridin-2-yl)amino)benzoate [00152] To a solution of methyl 4-[(6-chloro-3-nitro-2-pyridyl)amino]benzoate (45 g, 146 mmol) and phenylboronic acid (21.4 g, 176 mmol) in 1,4-dioxane (500 mL) and H ₂ O (100 mL) were added Pd(dppf)Cl ₂ (10.7 g, 14.6 mmol) and Cs ₂ CO ₃ (143 g, 439 mmol). The mixture was degassed and purged with N2 three times, and then stirred at 80 °C for 16 hr under N2 atmosphere. The reaction mixture was poured into H ₂ O (500 mL) and extracted with CH ₂ Cl ₂ (500 mL x 3). The combined organic layers were washed with brine (500 mL x 3), dried over anhydrous Na2SO4, filtered, and concentrated to dryness. The crude product was triturated with EtOAc at 25 ^o C for 30 min to give methyl 4-[(3-nitro-6-phenyl-2-pyridyl)amino]benzoate (35.2 g, yield: 69%) as a red solid. MS: m/z = 350.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 10.25 (s, 1H), 8.62 (d, J = 8.8 Hz, 1H), 8.15 - 8.10 (m, 2H), 8.00 (d, J = 8.4 Hz, 2H), 7.92 (d, J = 8.4 Hz, 2H), 7.67 (d, J = 8.8 Hz, 1H), 7.59 - 7.54 (m, 3H), 3.86 (s, 3H). [00153] Step 3: Methyl 4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyridin -3- yl)benzoate WSGR Docket No.62619-716.601 [00154] To a solution of methyl 4-[(3-nitro-6-phenyl-2-pyridyl)amino]benzoate (15 g, 42.9 mmol) in DMSO (150 mL) were added 2-aminopyridine-3-carbaldehyde (6.29 g, 51.5 mmol) and Na ₂ S ₂ O ₄ (15 g, 85.9 mmol). The reaction mixture was heated to 100°C for 16 hr. After cooling to 25 °C, the reaction mixture was diluted with H2O (200 mL) and extracted with CH ₂ Cl ₂ (200ml x 3), the combined organic layers were washed with brine brine (200ml x 2), dried over Na2SO4, filtered, and concentrated under reduced pressure to give a residue. The crude product was triturated with CH2Cl2 at 25 ^o C for 30 min to give methyl 4-[2-(2-amino-3- pyridyl)-5-phenyl-imidazo[4,5-b]pyridin-3-yl]benzoate (Intermediate 13, 12 g, yield: 66%) as a yellow solid. MS: m/z = 422.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 8.29 (d, J = 8.0 Hz, 1H), 8.12 (d, J = 8.4 Hz, 2H), 8.07 - 8.00 (m, 4H), 7.67 (d, J = 8.8 Hz, 2H), 7.49 - 7.44 (m, 2H), 7.42 - 7.38 (m, 1H), 7.23 (dd, J = 7.6, 1.6Hz, 1H), 6.89 (br s, 2H), 6.46 (dd, J = 7.6, 4.8 Hz, 1H), 3.90 (s, 3H). [00155] Step 4: (4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyridi n-3- yl)phenyl)methanol [00156] To a solution of Intermediate 13 (2.5 g, 5.9 mmol) in THF (25 mL) was added LiAlH4 (450 mg, 11.9 mmol) at 0 °C. After addition, the resulting mixture was stirred at 25 °C for 2 hr. After the reaction mixture was cooled to 0 °C, the reaction mixture was quenched with H ₂ O (100 mL), followed with15% aqueous NaOH (30 mL). Then the reaction mixture was filtered. The filter liquor was concentrated to dryness to give [4-[2-(2-amino-3-pyridyl)-5-phenyl- imidazo[4,5-b]pyridin-3-yl]phenyl]methanol (1.87 g, yield: 80%) as a yellow solid, which was directly used to the next step without further purification. MS: m/z = 394.1 [M + H] ⁺ . [00157] Step 5: 3-(3-(4-(Chloromethyl)phenyl)-5-phenyl-3H-imidazo[4,5-b]pyri din-2- yl)pyridin-2-amine [00158] To a solution of [4-[2-(2-amino-3-pyridyl)-5-phenyl-imidazo[4,5-b]pyridin-3- yl]phenyl]methanol (2.3 g, 5.9 mmol) in CH2Cl2 (25 mL) was added SOCl2 (2.1 g, 17.5 mmol). The mixture was stirred at 40°C for 1 hr. The reaction mixture was filtered. The filter liquor was concentrated to dryness to give 3-(3-(4-(chloromethyl)phenyl)-5-phenyl-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine (Intermediate 4, 1.71 g, yield: 71%) as a yellow solid. MS: m/z = 412.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ 8.29 (d, J = 8.4 Hz, 1H), 8.12 (d, J = 8.4 Hz, 2H), 8.07 - 8.00 (m, 4H), 7.67 (d, J = 8.4 Hz, 2H), 7.50 - 7.44 (m, 2H), 7.42 - 7.37 (m, 1H), 7.24 (d, J = 7.2 Hz, 1H), 6.88 (br s, 2H), 6.46 (dd, J = 4.8, 7.6 Hz, 1H), 3.90 (s, 2H). [00159] Intermediate 5: 3-(3-(4-((2,6-Diazaspiro[3.3]heptan-2-yl)methyl)phenyl)-5-ph enyl-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine WSGR Docket No.62619-716.601 [00160] Step 1: tert-Butyl 6-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyri din-3- yl)benzyl)-2,6-diazaspiro[3.3]heptane-2-carboxylate [00161] To a solution of Intermediate 4 (200 mg, 486 µmol) in MeCN (3 mL) were added K2CO3 (268 mg, 1.94 mmol), tert-butyl 2,6-diazaspiro[3.3]heptane-2-carboxylate (106 mg, 534 µmol) and NaI (7.28 mg, 48 µmol) at 25 °C. The reaction mixture was stirred at 80 °C for 3 hr. The reaction mixture was filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 0 – 7% MeOH in CH2Cl2) to give tert- butyl 6-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyri din-3-yl)benzyl)-2,6- diazaspiro[3.3]heptane-2-carboxylate (150 mg, yield: 54%) as a yellow solid. MS: m/z = 574.6 [M + H] ⁺ . [00162] Step 2: 3-(3-(4-((2,6-Diazaspiro[3.3]heptan-2-yl)methyl)phenyl)-5-ph enyl-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00163] To a solution of tert-butyl 6-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-2,6-diazaspiro[3.3]heptane-2-carboxyl ate (Intermediate 5, 150 mg, 261 µmol) in CH ₂ Cl ₂ (3 mL) was added TFA (1.54 g, 13.5 mmol) at 25 °C. The reaction mixture was stirred at 25 °C for 2 hr. The reaction mixture was concentrated to dryness to give 3-(3-(4- ((2,6-diazaspiro[3.3]heptan-2-yl)methyl)phenyl)-5-phenyl-3H- imidazo[4,5-b]pyridin-2- yl)pyridin-2-amine (Intermediate 5: 120 mg, TFA salt, yield: 81%) as a yellow solid. MS: m/z = 474.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 J = 8.4 Hz, 1H), 8.04 - 7.97 (m, 4H), 7.49 - 7.44 (m, 2H), 7.42 - 7.37 (m, 5H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 6.99 (br s, 2H), 6.39 (dd, J = 8.0, 5.2 Hz, 1H), 3.58 (s, 2H), 3.56 (s, 4H), 3.25 (s, 4H), 1.23 (s, 1H). [00164] Intermediate 6: (S)-3-(3-(4-((3-Aminopiperidin-1-yl)methyl)phenyl)-5-phenyl- 3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00165] Intermediate 6 was prepared in a manner similar to Intermediate 5. MS: m/z = 476.2 [M + H] ⁺ .1H NMR (400 MHz, Methanol-d4 8.32 (d, J = 8.4 Hz, 1H), 8.10 - 7.98 (m, 4H), WSGR Docket No.62619-716.601 7.94 (d, J = 8.4 Hz, 2H), 7.89 (dd, J = 7.6, 1.2 Hz, 1H), 7.74 (d, J = 8.4 Hz, 2H), 7.49 - 7.34 (m, 3H), 6.93 (dd, J = 7.6, 6.4 Hz, 1H), 4.62 (s, 2H), 3.89 - 3.56 (m, 3H), 3.28 - 3.12 (m, 2H), 2.26 - 1.99 (m, 3H), 1.90 - 1.66 (m, 1H). [00166] Intermediate 7: (S)-3-(3-(4-((3-Aminopyrrolidin-1-yl)methyl)phenyl)-5-phenyl -3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00167] Intermediate 7 was prepared in a manner similar to Intermediate 5. MS: m/z = 462.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol- d ₄ 8.32 (d, J = 8.4 Hz, 1H), 8.07 - 8.00 (m, 4H), 7.91 (d, J = 8.4 Hz, 2H), 7.84 (dd, J = 7.6, 1.2 Hz, 1H), 7.72 (d, J = 8.4 Hz, 2H), 7.48 - 7.38 (m, 3H), 6.91 (dd, J = 7.2, 7.2 Hz, 1H), 4.68 (s, 2H), 4.32 - 4.13 (m, 1H), 3.86 - 3.70 (m, 2H), 3.59 - 3.33 (m, 2H), 2.93 - 2.65 (m, 1H), 2.38 - 2.22 (m, 1H). [00168] Intermediate 8: 2-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyri din-3- yl)benzyl)-2-azaspiro[4.5]decan-8-amine [00169] Intermediate 8 was prepared in a manner similar to Intermediate 5. MS: m/z = 530.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 8.26 (d, J = 8.8 Hz, 1H), 8.06 - 7.94 (m, 4H), 7.50 - 7.37 (m, 7H), 7.15 (d, J = 7.2 Hz, 1H), 7.03 (br s, 2H), 6.44 - 6.32 (m, 1H), 4.40 - 4.36 (m, 1H), 4.18 - 4.09 (m, 6H), 1.65 - 1.45 (m, 6H), 1.31 - 1.22 (m, 4H). [00170] Intermediate 9: (R)-3-(3-(4-((3-Aminopiperidin-1-yl)methyl)phenyl)-5-phenyl- 3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine WSGR Docket No.62619-716.601 [00171] Intermediate 9 was prepared in a manner similar to Intermediate 5. MS: m/z = 476.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide- d ₆ 8.27 (d, J = 8.0 Hz, 1H), 8.04 - 7.97 (m, 4H), 7.50 - 7.44 (m, 6H), 7.42 - 7.38 (m, 1H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.01 (br s, 2H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 3.62 - 3.52 (m, 2H), 2.90 - 2.85 (m, 1H), 2.79 - 2.74 (m, 1H), 2.62 - 2.59 (m, 1H), 2.09 - 2.00 (m, 1H), 1.95 - 1.87 (m, 1H), 1.80 - 1.74 (m, 1H), 1.70 - 1.64 (m, 1H), 1.53 - 1.45 (m, 1H), 1.26 - 1.21 (m, 1H). [00172] Intermediate 10: (R)-3-(3-(4-((3-Aminopyrrolidin-1-yl)methyl)phenyl)-5-phenyl -3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00173] Intermediate 10 was prepared in a manner similar to Intermediate 5. MS: m/z = 462.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide- d6 8.27 (d, J = 8.0 Hz, 1H), 8.04 - 7.97 (m, 4H), 7.52 - 7.44 (m, 6H), 7.43 - 7.34 (m, 1H), 7.6 (dd, J = 7.6, 2.0 Hz, 1H), 7.00 (br s, 2H), 6.40 (dd, J = 8.0, 5.2 Hz, 1H), 3.69 (s, 2H), 3.60 - 3.57 (m, 2H), 2.75 - 2.66 (m, 2H), 2.46 - 2.40 (m, 1H), 2.18 - 2.08 (m, 1H), 1.66 - 1.56 (m, 1H). [00174] Intermediate 11: 3-(3-(4-((3-Aminoazetidin-1-yl)methyl)phenyl)-5-phenyl-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00175] Intermediate 11 was prepared in a manner similar to Intermediate 5. MS: m/z = 448.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide- d ₆ 8.26 (d, J = 8.4 Hz, 1H), 8.04 - 7.96 (m, 4H), 7.49 - 7.36 (m, 7H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 7.00 (br s, 2H), 6.39 (dd, J = 8.0, 4.8 Hz, 1H), 3.61 (s, 2H), 3.52 - 3.48 (m, 2H), 3.47 - 3.38 (m, 3H), 2.72 - 2.65 (m, 2H). [00176] Intermediate 12: 3-(3-(4-((1,4-Diazepan-1-yl)methyl)phenyl)-5-phenyl-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine WSGR Docket No.62619-716.601 [00177] Step 1: tert-Butyl 4-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyri din-3- yl)benzyl)-1,4-diazepane-1-carboxylate [00178] To a solution of Intermediate 4 (1 g, 2.43 mmol), tert-butyl 1,4-diazepane-1- carboxylate (584 mg, 2.92 mmol) in ACN (20 mL) were added NaI (36.4 mg, 243 µmol) and K ₂ CO ₃ (671 mg, 4.86 mmol). The mixture was stirred at 80 °C for 2 hr. The reaction mixture was concentrated directly. The residue was purified by silica gel flash chromatography (Eluent of 0~10% MeOH in CH2Cl2) to give tert-butyl 4-[[4-[2-(2-amino-3-pyridyl)-5-phenyl- imidazo[4,5-b]pyridin-3-yl]phenyl]methyl]-1,4-diazepane-1-ca rboxylate (520 mg, yield: 33%) as a light-yellow solid, which was used directly in the next step without further purification. MS: m/z = 576.4 [M + H] ⁺ . [00179] Step 2: 3-(3-(4-((1,4-Diazepan-1-yl)methyl)phenyl)-5-phenyl-3H-imida zo[4,5- b]pyridin-2-yl)pyridin-2-amine [00180] To a solution of tert-butyl 4-[[4-[2-(2-amino-3-pyridyl)-5-phenyl-imidazo[4,5- b]pyridin-3-yl]phenyl]methyl]-1,4-diazepane-1-carboxylate (520 mg, 0.903 mmol) in HCl/1,4- dioxane (4M, 10 mL). The mixture was stirred at 25 C for 1 hr. The reaction mixture was concentrated directly to give the crude product (310 mg HCl salt, yield: 67%). The crude (100 mg) was purified by prep-HPLC (column: Phenomenex C18150*25mm 10 µm; mobile phase: [water (NH4HCO3)-ACN]; B%: 28% - 58%, 8 min) to give 3-[3-[4-(1,4-diazepan-1- ylmethyl)phenyl]-5-phenyl-imidazo[4,5-b]pyridin-2-yl]pyridin -2-amine (Intermediate 12, 9 mg) as light-yellow solid. MS: m/z = 476.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) 8.4 (d, J = 8.4 Hz, 1H), 8.04 - 7.97 (m, 4H), 7.52 - 7.39 (m, 7H), 7.14 (dd, J = 7.6, 1.8 Hz, 1H), 7.05 (br s, 2H), 6.39 - 6.34 (m, 1H), 3.72 (s, 2H), 2.82 (t, J = 6.4 Hz, 2H), 2.78 - 2.74 (m, 2H), 2.67 (t, J = 6.4 Hz, 2H), 2.66 - 2.57 (m, 2H), 1.78 - 1.64 (m, 2H). [00181] Intermediate 13: 7-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyri din-3- yl)benzyl)-7-azaspiro[3.5]nonan-2-amine WSGR Docket No.62619-716.601 [00182] Intermediate 13 was prepared in a manner similar to Intermediate 12. MS: m/z = 516.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ J = 8.0 Hz, 1H), 8.06 - 7.95 (m, 4H), 7.55 - 7.35 (m, 7H), 7.18 - 7.12 (m, 1H), 7.01 (br s, 2H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 3.71 - 3.58 (m, 1H), 3.52 (s, 2H), 3.01 - 2.98 (m, 4H), 2.41 - 2.20 (m, 2H), 2.14 - 2.05 (m, 2H), 1.90 - 1.80 (m, 2H), 1.67 - 1.53 (m, 2H). [00183] Intermediate 14: 2-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyri din-3- yl)benzyl)-2-azaspiro[3.3]heptan-6-amine [00184] Intermediate 14 was prepared in a manner similar to Intermediate 5. MS: m/z = 488.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ 8.20 (d, J = 8.8 Hz, 1H), 8.05 - 8.01 (m, 2H), 7.99 (dd, J = 5.2, 1.6 Hz, 1H), 7.95 (d, J = 8.4 Hz, 1H), 7.58 - 7.50 (m, 2H), 7.43 - 7.39 (m, 2H), 7.34 (dd, J = 7.6, 2.0 Hz, 1H), 6.49 (dd, J = 7.6, 4.8 Hz, 1H), 6.21 - 6.17 (m, 2H), 5.65 (dd, J = 7.6, 4.4 Hz, 1H), 4.26 - 4.18 (m, 1H), 4.00 (s, 2H), 3.77 (s, 2H), 3.66 (s, 2H), 2.65 – 2.60 (m, 2H), 2.22 - 2.17 (m, 2H). [00185] Intermediate 15: 2-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyri din-3- yl)benzyl)-2-azaspiro[3.5]nonan-7-amine [00186] Intermediate 15 was prepared in a manner similar to Intermediate 12. MS: m/z = 516.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 J = 8.4 Hz, 1H), 8.04 - 7.97 (m, 4H), 7.49 - 7.44 (m, 2H), 7.43 - 7.37 (m, 5H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.00 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.65 (s, 2H), 3.20 - 3.12 (m, 1H), 2.95 (s, 2H), 2.90 (s, 2H), 1.86 - 1.80 (m, 2H), 1.65 - 1.57 (m, 2H), 1.42 - 1.34 (m, 2H), 1.11 - 0.95 (m, 2H). [00187] Intermediate 16: 3-(3-(4-((2,7-Diazaspiro[3.5]nonan-7-yl)methyl)phenyl)-5-phe nyl- 3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine WSGR Docket No.62619-716.601 [00188] Intermediate 16 was prepared in a manner similar to Intermediate 12. MS: m/z = 502.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 J = 8.4 Hz, 1H), 8.05 - 7.97 (m, 4H), 7.49 - 7.39 (m, 7H), 7.18 - 7.12 (dd, J = 7.6, 1.6 Hz, 1H), 7.02 (br s, 2H), 6.36 (dd, J = 7.6, 5.2 Hz, 1H), 3.58 - 3.41 (m, 6H), 2.38 - 2.26 (m, 4H), 1.71 – 1.68 (m, 4H). [00189] Intermediate 17: 3-(3-(4-((2,8-Diazaspiro[4.5]decan-8-yl)methyl)phenyl)-5-phe nyl-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00190] Intermediate 17 was prepared in a manner similar to Intermediate 12. MS: m/z = 516.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ J = 8.4 Hz, 1H), 8.02 (d, J = 7.2 Hz, 2H), 7.97 (dd, J = 4.8, 1.6 Hz, 1H), 7.93 (d, J = 8.4 Hz, 1H), 7.52 (d, J = 8.4 Hz, 2H), 7.45 - 7.34 (m, 5H), 7.31 (dd, J = 6.8, 1.6 Hz, 1H), 6.45 (dd, J = 7.6, 4.8 Hz, 1H), 3.62 (s, 2H), 3.10 (t, J = 7.2 Hz, 2H), 2.85 (s, 2H), 2.50 (m, 4H), 1.75 (t, J = 7.2 Hz, 2H), 1.65 ( t, J = 5.6 Hz, 4H). [00191] Intermediate 18: 3-(3-(4-((3,9-diazaspiro[5.5]undecan-3-yl)methyl)phenyl)-5-p henyl- 3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00192] Intermediate 18 was prepared in a manner similar to Intermediate 12. MS: m/z = 530.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) 2H), 8.38 (dd, J = 8.4 Hz, 1H), 8.13 - 8.11 (m, 1H), 8.08 - 8.05 (m, 4H), 7.86 - 7.77 (m, 3H), 7.67 (d, J = 8.0 Hz, 2H), 7.51 - 7.46 (m, 2H), 7.45 - 7.41 (m, 1H), 6.86 - 6.78 (m, 1H), 4.41 ( d, J = 4.4 Hz, 2H), 3.21 - 3.15 (m, 2H), 3.09 - 3.01 (m, 6H), 1.91 - 1.85 (m, 2H), 1.82 - 1.71 (m, 4H), 1.54 – 1.53 (m, 2H). WSGR Docket No.62619-716.601 [00193] Intermediate 19: 3-(3-(4-((2,6-Diazaspiro[3.4]octan-6-yl)methyl)phenyl)-5-phe nyl-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00194] Intermediate 19 was prepared in a manner similar to Intermediate 5. MS: m/z = 488.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) J = 8.4 Hz, 1H), 8.06 - 7.89 (m, 4H), 7.51 (d, J = 8.0 Hz, 2H), 7.45 - 7.40 (m, 3H), 7.39 - 7.30 (m, 3H), 6.48 (dd, J = 7.6, 5.2 Hz, 1H), 3.99 (d, J = 2.4 Hz, 2H), 3.72 (s, 2H), 2.87 (s, 2H), 2.71 - 2.61 (m, 2H), 2.18 (t, J = 7.2 Hz, 2H), 1.28 - 1.25 (m, 2H). [00195] Intermediate 20: 3-(3-(4-((2,7-Diazaspiro[4.4]nonan-2-yl)methyl)phenyl)-5-phe nyl- 3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00196] Intermediate 20 was prepared in a manner similar to Intermediate 12. MS: m/z = 502.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6) 8.60 - 8.35 (m, 2H), 8.38 (d, J = 8.4 Hz, 1H), 8.16 (dd, J = 6.4, 1.6 Hz, 1H), 8.08 - 8.05 (m, 3H), 7.98 - 7.83 (m, 3H), 7.66 (d, J = 8.4 Hz, 2H), 7.52 - 7.40 (m, 3H), 7.02 - 6.92 (m, 1H), 4.54 - 4.43 (m, 2H), 3.64 - 3.47 (m, 2H), 3.43 - 3.27 (m, 3H), 3.25 - 3.18 (m, 3H), 2.31 - 2.14 (m, 2H), 2.11 - 1.96 (m, 2H). [00197] Intermediate 21: 3-(3-(4-((2,8-Diazaspiro[4.5]decan-2-yl)methyl)phenyl)-5-phe nyl-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00198] Intermediate 21 was prepared in a manner similar to Intermediate 12. MS: m/z = 516.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4) J = 8.8 Hz, 1H), 8.10 - 8.01 (m, 4H), WSGR Docket No.62619-716.601 7.96 - 7.87 (m, 3H), 7.72 (d, J = 8.0 Hz, 2H), 7.49 - 7.40 (m, 3H), 6.96 - 6.87 (m, 1H), 4.67 - 4.54 (m, 2H), 3.75 - 3.65 (m, 2H), 3.51 (d, J = 10.0 Hz, 1H), 3.35 (s, 2H), 3.32 - 3.20 (m, 3H), 2.32 - 2.23 (m, 1H), 2.15 - 2.05 (m, 2H), 2.04 - 1.96 (m, 3H). [00199] Intermediate 22: 3-(3-(4-((2,7-Diazaspiro[4.5]decan-2-yl)methyl)phenyl)-5-phe nyl-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00200] Intermediate 22 was prepared in a manner similar to Intermediate 12. MS: m/z = 516.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ J = 8.4 Hz, 1H), 8.09 - 8.00 (m, 4H), 7.93 (d, J = 8.4 Hz, 2H), 7.89 (d, J = 7.2 Hz, 1H), 7.72 (d, J = 8.0 Hz, 2H), 7.49 - 7.37 (m, 3H), 6.99 - 6.85 (m, 1H), 4.62 (d, J = 11.6 Hz, 2H), 3.78 - 3.72 (m, 1H), 3.65 - 3.47 (m, 2H), 3.44 - 3.38 (m, 1H), 3.35 (s, 2H), 3.18 - 3.13 (m, 2H), 2.26 - 2.13 (m, 1H), 2.11 - 2.01 (m, 1H), 1.95 - 1.86 (m, 4H). [00201] Intermediate 23: 3-(3-(4-((2,7-Diazaspiro[3.5]nonan-2-yl)methyl)phenyl)-5-phe nyl- 3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00202] Intermediate 23 was prepared in a manner similar to Intermediate 12. MS: m/z = 502.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 2H), 8.36 (d, J = 8.8 Hz, 1H), 8.33 - 8.18 (m, 1H), 8.13 (dd, J = 6.8, 1.2 Hz, 1H), 8.04 – 8.08 (m, 3H), 7.83 - 7.75 (m, 3H), 7.65 (d, J = 8.4 Hz, 2H), 7.52 - 7.46 (m, 2H), 7.45 - 7.39 (m, 1H), 6.92 - 6.83 (m, 1H), 4.50 (d, J = 6.0 Hz, 2H), 3.96 (d, J = 6.0 Hz, 4H), 3.07 - 3.10 (m, 2H), 2.95 – 3.02 (m, 2H), 2.10 - 2.17 (m, 2H), 1.97 – 2.04 (m, 2H). [00203] Intermediate 24: (R)-3-(3-(4-((2,7-Diazaspiro[4.4]nonan-2-yl)methyl)phenyl)-5 -phenyl- 3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine WSGR Docket No.62619-716.601 [00204] Step 1: tert-Butyl (R)-7-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-2,7-diazaspiro[4.4]nonane-2-carboxyla te [00205] To a solution of Intermediate 4 (1.0 g, 2.43 mmol) in DMF (10 mL) were added K ₂ CO ₃ (671 mg, 4.86 mmol) and tert-butyl (R)-2,7-diazaspiro[4.4]nonane-2-carboxylate (604 mg, 2.67 mmol). The mixture was stirred at 25 °C for 16 hr. The reaction mixture was diluted with H2O (10 mL) at 25 °C and extracted with CH ₂ Cl ₂ (20 mL x 3). The combined organic layers were washed with brine (30 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure to give a residue. The crude was purified by silica gel flash chromatography (Eluent of 1~5% MeOH in CH ₂ Cl ₂ ) to give tert-butyl (R)-7-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-2,7-diazaspiro[4.4]nonane -2-carboxylate (920 mg, yield: 63%) as a yellow solid. MS: m/z = 602.6 [M + H] ⁺ . [00206] Step 2: (R)-3-(3-(4-((2,7-Diazaspiro[4.4]nonan-2-yl)methyl)phenyl)-5 -phenyl-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00207] A solution of tert-butyl (R)-7-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)-2,7-diazaspiro[4.4]nonane-2-carboxyla te (700 mg, 1.16 mmol) in 4 M HCl and 1,4-dioxane (7 mL) was stirred at 25 °C for 2 hr. The reaction was concentrated under reduced pressure to give (R)-3-(3-(4-((2,7-diazaspiro[4.4]nonan-2-yl)methyl)phenyl)-5 -phenyl- 3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (Intermediate 24, 600 mg, HCl salt, yield: 96%) as a yellow solid. MS: m/z = 502.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ 12.00 - 11.77 (m, 1H), 9.73 - 9.52 (m, 2H), 8.58 - 8.44 (m, 1H), 8.38 (d, J = 8.4 Hz, 1H), 8.16 (dd, J =6.0, 1.6 Hz, 1H), 8.04 – 8.09 (m, 3H), 7.92 - 7.85 (m, 3H), 7.66 (d, J = 8.4 Hz, 2H), 7.52 - 7.46 (m, 2H), 7.45 - 7.40 (m, 1H), 7.00 - 6.92 (m, 1H), 4.57 - 4.41 (m, 2H), 3.50-3.58 (m, 4H), 3.41 - 3.33 (m, 2H), 3.25 - 3.22 (m, 2H), 2.28 - 2.13 (m, 2H), 2.10 - 1.97 (m, 2H). [00208] Intermediate 25: 3-(3-(4-(2,9-Diazaspiro[5.5]undecan-9-ylmethyl)phenyl)-5-phe nyl-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine WSGR Docket No.62619-716.601 [00209] Intermediate 25 was prepared in a manner similar to Intermediate 24. MS: m/z = 530.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ 2H), 8.52 (br s, 1H), 8.38 (d, J = 8.4 Hz, 1H), 8.16 (d, J = 6.0 Hz, 1H), 8.12 - 8.02 (m, 3H), 7.91 - 7.81 (m, 3H), 7.73 - 7.62 (m, 2H), 7.52 - 7.40 (m, 3H), 6.93 - 6.84 (m, 1H), 4.41 (d, J = 5.2 Hz, 2H), 3.21 - 3.09 (m, 5H), 2.99 - 2.90 (m, 2H), 2.87 - 2.75 (m, 1H), 2.13 - 2.09 (m, 1H), 2.00 - 1.88 (m, 1H), 1.86 - 1.73 (m, 2H), 1.72 - 1.56 (m, 3H), 1.45 - 1.40 (m, 1H). [00210] Intermediate 26: 3-(3-(4-(((3S,5S)-3,5-Dimethylpiperazin-1-yl)methyl)phenyl)- 5- phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00211] Intermediate 26 was prepared in a manner similar to Intermediate 24. MS: m/z = 490.6 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ J = 8.4 Hz, 1H), 8.08 - 7.95 (m, 4H), 7.52 - 7.35 (m, 7H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 7.04 (br s, 2H), 6.40 - 6.34 (m, 1H), 3.54 (d, J = 14.0 Hz, 1H), 3.45 – 3.40 (m, 1H), 3.10 – 3.04 (m, 2H), 2.41 - 2.33 (m, 2H), 2.06 – 2.00 (m, 2H), 1.04 (d, J = 6.4 Hz, 6H). [00212] Intermediate 27: 3-(3-(4-(((3R,5R)-3,5-Dimethylpiperazin-1-yl)methyl)phenyl)- 5- phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00213] Step 1: tert-Butyl (2R,6R)-4-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4, 5- b]pyridin-3-yl)benzyl)-2,6-dimethylpiperazine-1-carboxylate [00214] To a solution of Intermediate 4 (1.06 g, 2.57 mmol) and tert-butyl (2R,6R)-2,6- dimethylpiperazine-1-carboxylate (500 mg, 2.33 mmol) in DMF (10 mL) was added DIEA (905 mg, 7.0 mmol). The mixture was stirred at 80 °C for 16 hr. The mixture was quenched with H2O (40 mL) and extracted with EtOAc (40 mL x 3). The combined organic phase was dried over anhydrous Na ₂ SO ₄ , filtered, and concentrated. The residue was purified by silica gel flash chromatography (Eluent of 0~9% MeOH in CH2Cl2) to give tert-butyl (2R,6R)-4-(4-(2-(2- aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyridin-3-yl)be nzyl)-2,6-dimethylpiperazine-1- carboxylate (Intermediate 27, 1 g, yield: 69.4%) as a yellow solid. MS: m/z = 590.4 [M + H] ⁺ . WSGR Docket No.62619-716.601 1H NMR (400 MHz, Dimethylsulfoxide-d6 8.27 (d, J = 8.4 Hz, 1H), 8.05 - 7.98 (m, 4H), 7.52 - 7.43 (m, 6H), 7.42 - 7.36 (m, 1H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.04 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.83 - 3.74 (m, 2H), 3.65 (d, J = 13.6 Hz, 1H), 3.48 (d, J = 13.6 Hz, 1H), 3.35 – 3.39 (m, 2H), 2.27-2.19 (m, 2H), 1.42 - 1.41 (m, 1H), 1.40 (s, 9H), 1.23 (d, J = 6.4 Hz, 6H). [00215] Step 2: 3-(3-(4-(((3R,5R)-3,5-Dimethylpiperazin-1-yl)methyl)phenyl)- 5-phenyl-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00216] A solution of tert-butyl (2R,6R)-4-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-2,6-dimethylpiperazine-1- carboxylate (100 mg, 169 µmol) in HCl/1,4-dioxane (4M, 1 mL) was stirred at 25 °C for 0.5 hr. The mixture was filtered to give 3-(3-(4-(((3R,5R)-3,5-dimethylpiperazin-1-yl)methyl)phenyl)- 5-phenyl-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine (Intermediate 27, 84 mg HCl salt, yield: 95%) as a yellow solid. MS: m/z = 490.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 0.5H), 10.79 - 10.27 (m, 0.5H), 10.07 - 9.71 (m, 1H), 8.65 - 8.51 (m, 1H), 8.38 (d, J = 8.4 Hz, 1H), 8.16 (d, J = 6.0 Hz, 1H), 8.11 - 7.95 (m, 4H), 7.93 - 7.82 (m, 3H), 7.68 (d, J = 8.0 Hz, 2H), 7.51 - 7.42 (m, 3H), 7.04 (t, J = 6.8 Hz, 1H), 4.50 - 4.25 (m, 2H), 3.44-3.32 (m, 2H), 3.20-3.01 (m, 2H), 2.91 – 2.87 (m, 1H), 2.75 – 2.71 (m, 1H), 1.60 - 1.31 (m, 6H). [00217] Intermediate 28: (R)-3-(3-(4-((3-Methylpiperazin-1-yl)methyl)phenyl)-5-phenyl -3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00218] Intermediate 28 was prepared in a manner similar to Intermediate 24. MS: m/z = 476.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 J = 8.4 Hz, 1H), 8.08 - 7.95 (m, 4H), 7.52 - 7.35 (m, 7H), 7.15 (d, J = 6.0 Hz, 1H), 7.04 (br s, 2H), 6.40 - 6.34 (m, 1H), 3.53 (s, 2H), 2.87 - 2.77 (m, 1H), 2.75 - 2.62 (m, 4H), 2.02 - 1.91 (m, 1H), 1.68 - 1.58 (m, 1H), 0.92 (d, J = 6.0 Hz, 3H). [00219] Intermediate 29: 3-(3-(4-((3,8-Diazabicyclo[3.2.1]octan-3-yl)methyl)phenyl)-5 -phenyl- 3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine WSGR Docket No.62619-716.601 [00220] Intermediate 29 was prepared in a manner similar to Intermediate 24. MS: m/z = 488.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4 8.34 – 8.28 (m, 1H), 8.05 - 7.95 (m, 4H), 7.90- 7.85 (m, 3H), 7.65 (d, J = 8.0 Hz, 2H), 7.48 – 7.37 (m, 3H), 6.90 (t, J = 6.8 Hz, 1H), 4.35 – 4.25 (m, 4H),3.50 – 3.40 (m, 4H),2.41 (d, J = 8.4 Hz, 2H), 2.25 – 2.16 (m, 2H). [00221] Intermediate 30: 3-(3-(4-((3,8-Diazabicyclo[3.2.1]octan-8-yl)methyl)phenyl)-5 -phenyl- 3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00222] Intermediate 30 was prepared in a manner similar to Intermediate 24. MS: m/z = 488.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ 8.55 (br s, 1H), 8.38 (d, J = 8.0 Hz, 1H), 8.13 – 8.07 (m, 1H), 8.06 – 8.00 (m, 5H), 7.98 – 7.94 (m, 1H), 7.69 (d, J = 8.0 Hz, 2H), 7.50 – 7.40 (m, 3H), 6.94 (t, J = 7.2 Hz, 1H), 4.39 - 4.33 (m, 2H), 4.01 (s, 2H), 3.95 – 3.89 (m, 3H), 3.42 – 3.39 (m, 3H), 2.47 – 2.38 (m, 2H). [00223] Intermediate 31: 1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyri din-3- yl)benzyl)azepan-4-amine [00224] Intermediate 31 was prepared in a manner similar to Intermediate 27. MS: m/z = 490.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 J = 8.4 Hz, 1H), 8.36 - 8.18 (m, 3H), 8.14 (J = 7.6 Hz, 1H), 8.12 - 7.97 (m, 3H), 7.96 - 7.80 (m, 3H), 7.67 (d, J = 8.4 Hz, 2H), 7.52 - 7.38 (m, 3H), 6.93 - 6.84 (m, 1H), 4.52 - 4.33 (m, 2H), 3.40 - 3.38 (m, 2H), 3.21 - 3.12 (m, 2H), 3.09 - 2.96 (m, 1H), 2.26 - 1.98 (m, 4H), 1.93 - 1.80 (m, 1H), 1.75 - 1.61 (m, 1H). WSGR Docket No.62619-716.601 [00225] Intermediate 32: 1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyri din-3- yl)benzyl)azepan-3-amine [00226] Intermediate 32 was prepared in a manner similar to Intermediate 12. MS: m/z = 490.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ J = 8.4 Hz, 1H), 8.05 - 7.98 (m, 4H), 7.53 - 7.37 (m, 7H), 7.16 - 7.12 (m, 1H), 7.07 (br s, 2H), 6.38 (dd, J = 7.6 , 4.8 Hz, 1H), 3.77 - 3.72 (m, 2H), 3.62 - 3.53 (m, 1H), 2.89 - 2.78 (m, 2H), 2.65 - 2.61 (m, 2H), 2.59 - 2.53 (m, 2H), 1.82 - 1.73 (m, 1H), 1.67 - 1.48 (m, 4H), 1.46 - 1.25 (m, 1H). [00227] Intermediate 33: (S)-3-(3-(4-((3-Methylpiperazin-1-yl)methyl)phenyl)-5-phenyl -3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00228] Intermediate 33 was prepared in a manner similar to Intermediate 24. MS: m/z = 476.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4 J = 8.4 Hz, 1H), 8.07 - 7.99 (m, 4H), 7.94 - 7.84 (m, 3H), 7.73 (d, J = 8.4 Hz, 2H), 7.50 - 7.37 (m, 3H), 6.96 - 6.88 (m, 1H), 4.57 (s, 1H), 4.60 - 4.53 (m, 1H), 3.94 - 3.83 (m, 1H), 3.81 - 3.69 (m, 3H), 3.68 - 3.56 (m, 1H), 3.54 - 3.41 (m, 1H), 1.45 (d, J = 6.8 Hz, 3H). [00229] Intermediate 34: 3-(3-(4-(4,7-Diazaspiro[2.5]octan-7-ylmethyl)phenyl)-5-pheny l-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00230] Intermediate 34 was prepared in a manner similar to Intermediate 24. MS: m/z = 488.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ J = 8.4 Hz, 1H), 8.09 - 7.92 (m, WSGR Docket No.62619-716.601 4H), 7.56 - 7.33 (m, 7H), 7.14 (dd, J = 7.8, 1.8 Hz, 1H), 7.05 (br s, 2H), 6.34 (dd, J = 7.6, 4.8 Hz, 1H), 3.52 (s, 2H), 2.76 (t, J = 4.8 Hz, 2H), 2.44 - 2.32 (m, 2H), 2.18 (s, 3H), 0.47 - 0.38 (m, 2H), 0.35 - 0.25 (m, 2H). [00231] Intermediate 35: 3-(3-(4-(((1S,4S)-2,5-Diazabicyclo[2.2.1]heptan-2-yl)methyl) phenyl)- 5-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00232] Intermediate 35 was prepared in a manner similar to Intermediate 27. MS: m/z = 474.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ 2H), 8.55 – 8.39 (m, 1H), 8.38 (d, J = 8.4 Hz, 1H), 8.14 (d, J = 5.2 Hz, 1H), 8.11 - 8.01 (m, 3H), 7.94 (d, J = 8.0 Hz, 2H), 7.84 (d, J = 7.2 Hz, 1H), 7.69 (d, J = 8.4 Hz, 2H), 7.54 - 7.40 (m, 3H), 6.91 - 6.87 (m, 1H), 4.68 - 4.40 (m, 4H), 3.99 - 3.94 (m, 1H), 3.80 - 3.75 (m, 2H), 3.42 - 3.40 (m, 1H), 2.60 - 2.52 (m, 1H), 2.20 - 2.06 (m, 1H). [00233] Intermediate 36: 3-(3-(4-(((1R,4R)-2,5-Diazabicyclo[2.2.1]heptan-2-yl)methyl) phenyl)- 5-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00234] Intermediate 36 was prepared in a manner similar to Intermediate 24. MS: m/z = 474.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ J = 8.4 Hz, 1H), 8.06 - 8.00 (m, 6H), 7.88 (dd, J = 7.6, 1.6 Hz, 1H), 7.73 (d, J = 8.4 Hz, 2H), 7.46 - 7.40 (m, 3H), 6.92 (dd, J = 7.6, 6.4 Hz, 1H), 4.84 - 4.81 (m, 1H), 4.75 - 4.65 (m, 2H), 4.14 (d, J = 12.8 Hz, 1H), 3.96 - 3.92 (m, 1H), 3.74 - 3.71 (m, 1H), 3.62 - 3.60 (m, 1H), 3.38 - 3.32 (m, 1H), 2.87 - 2.82 (m, 1H), 2.39 - 2.36 (m, 1H). [00235] Intermediate 37: 3-(3-(4-(((3S,5R)-3,5-Dimethylpiperazin-1-yl)methyl)phenyl)- 5- phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine WSGR Docket No.62619-716.601 [00236] Intermediate 37 was prepared in a manner similar to Intermediate 24. MS: m/z = 490.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 J = 8.4 Hz, 1H), 7.97 - 8.04 (m, 4H), 7.42 - 7.48 (m, 6H), 7.37 - 7.42 (m, 1H), 7.15 (dd, J = 7.6, 2.0 Hz, 1H), 7.05 (br s, 2H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 3.52 (s, 2H), 2.73 - 2.79 (m, 2H), 2.64 - 2.67 (m, 2H), 1.56 - 1.50 (m, 2H), 0.91 (d, J = 6.0 Hz, 6H). [00237] Intermediate 38: 3-(3-(4-((2,5-Diazabicyclo[2.2.2]octan-2-yl)methyl)phenyl)-5 -phenyl- 3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00238] Intermediate 38 was prepared in a manner similar to Intermediate 12. MS: m/z = 488.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 2H), 8.56 - 8.40 (m, 1H), 8.38 (d, J = 8.4 Hz, 1H), 8.15 (dd, J = 6.0, 1.2 Hz, 1H), 8.10 - 7.99 (m, 5H), 7.86 (dd, J = 7.2, 1.2 Hz, 1H), 7.68 (d, J = 8.4 Hz, 2H), 7.51 - 7.46 (m, 2H), 7.46 - 7.40 (m, 1H), 6.91 (dd, J = 7.6, 6.4 Hz, 1H), 4.62 (br s, 2H), 4.01 - 3.79 (m, 4H), 3.76 - 3.70 (m, 2H), 2.21 (m, 2H), 1.97 - 1.80 (m, 2H). [00239] Intermediate 39: 3-(3-(4-((2,6-Diazaspiro[3.4]octan-2-yl)methyl)phenyl)-5-phe nyl-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00240] Intermediate 39 was prepared in a manner similar to Intermediate 5. MS: m/z = 488.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ J = 8.4 Hz, 1H), 8.06 - 7.95 (m, 4H), 7.51 - 7.36 (m, 7H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 6.99 (br s, 2H), 6.39 (dd, J = 7.6, 4.8 WSGR Docket No.62619-716.601 Hz, 1H), 3.63 (s, 2H), 3.16 - 3.10 (m, 4H), 2.88 (s, 2H), 2.74 (t, J = 6.8 Hz, 2H), 1.82 (t, J = 6.8 Hz, 2H), 1.25 - 1.22 (m, 1H). [00241] Intermediate 40: 3-(3-(4-((2,6-Diazaspiro[3.5]nonan-2-yl)methyl)phenyl)-5-phe nyl-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00242] Intermediate 40 was prepared in a manner similar to Intermediate 12. MS: m/z = 502.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ J = 8.4 Hz, 1H), 8.03 - 7.97 (m, 5H), 7.50 - 7.39 (m, 6H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 7.01 (br s, 2H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 3.66 (s, 2H), 3.04 (d, J = 7.2 Hz, 2H), 2.85 (d, J = 6.8 Hz, 2H), 2.78 (s, 2H), 2.62 - 2.58 (m, 2H), 1.64- 1.60 (m, 2H), 1.40- 1.35 (m, 2H). [00243] Intermediate 41: (S)-3-(3-(4-((2,7-Diazaspiro[4.4]nonan-2-yl)methyl)phenyl)-5 -phenyl- 3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00244] Intermediate 41 was prepared in a manner similar Intermediate 24. MS: m/z = 502.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 8.66 - 8.50 (m, 2H), 8.38 (d, J = 8.4 Hz, 1H), 8.17 (dd, J = 6.4, 1.6 Hz, 1H), 8.08 - 8.05 (m, 3H), 7.93 - 7.86 (M, 3H), 7.66 (d, J = 8.4 Hz, 2H), 7.54 - 7.40 (m, 3H), 7.00 - 6.95 (m, 1H), 3.55 - 3.50 (m, 1H), 3.40 - 3.17 (m, 8H), 2.33 - 1.95 (m, 5H). [00245] Intermediate 42: 3-(3-(4-(Piperazin-1-ylmethyl)phenyl)-3H-imidazo[4,5-b]pyrid in-2- yl)pyridin-2-amine WSGR Docket No.62619-716.601 [00246] Step 1: tert-Butyl 4-(4-nitrobenzyl)piperazine-1-carboxylate [00247] To a solution of 1-(bromomethyl)-4-nitro-benzene (25 g, 116 mmol) in ACN (250 mL) were added tert-butyl piperazine-1-carboxylate (25.8 g, 139 mmol) and K ₂ CO ₃ (31.9 g, 231 mmol) at 20 °C. The mixture was stirred at 20 °C for 12 hr. The reaction mixture was filtered. The filtrate was concentrated to give tert-butyl 4-(4-nitrobenzyl)piperazine-1-carboxylate (37 g, yield: 99%) as a white solid, which was used in the next step without further purification. MS: m/z = 322.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 J = 8.8 Hz, 2H), 7.60 (d, J = 8.8 Hz, 2H), 3.62 (s, 2H), 3.32 - 3.36 (m, 4H), 2.38-2.28 (m, 4H), 1.39 (s, 9H). [00248] Step 2: tert-Butyl 4-(4-aminobenzyl)piperazine-1-carboxylate [00249] To a solution of tert-butyl 4-(4-nitrobenzyl)piperazine-1-carboxylate(20 g, 62.2 mmol) in EtOH (150 mL) and H2O (50 mL) were added Fe (17.3 g, 311 mmol) and NH4Cl (13.3 g, 249 mmol) at 25 °C. The mixture was stirred at 90 °C for 2 hr. The reaction mixture was filtered and concentrated to give tert-butyl 4-(4-aminobenzyl)piperazine-1-carboxylate (17 g, crude) as a yellow oil, which was used in the next step without further purification. MS: m/z = 292.9 [M+ H] ⁺ . [00250] Step 3: tert-Butyl 4-(4-((3-nitropyridin-2-yl)amino)benzyl)piperazine-1-carboxy late [00251] To a solution of 2-chloro-3-nitro-pyridine (10 g, 63 mmol) in DMSO (200 mL) were added tert-butyl 4-(4-aminobenzyl)piperazine-1-carboxylate(15.3 g, 52.5 mmol) and DIEA (13.5 g, 105 mmol) at 25 °C. The mixture was stirred at 80 °C for 12 hr. The reaction mixture was concentrated, diluted with H2O (200 mL), and extracted with CH2Cl2 (200 mL x 2). The combined organic layers were washed with brine (200 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 10~30% EtOAc in petroleum ether) to give tert-butyl 4-(4-((3- nitropyridin-2-yl)amino)benzyl)piperazine-1-carboxylate (11g, yield: 45%) as a red solid. MS: WSGR Docket No.62619-716.601 m/z = 413.9 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 2H), 7.60 (d, J = 8.4 Hz, 2H), 7.29 (d, J = 8.4 Hz, 2H), 6.98 (dd, J = 8.4, 4.8 Hz, 1H), 3.46 (s, 2H), 3.29 - 3.32 (m, 4H), 2.29 - 2.35 (m, 4H), 1.39 (s, 9H). [00252] Step 4: tert-Butyl 4-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperazine-1-carboxylate [00253] To a solution of tert-butyl 4-(4-((3-nitropyridin-2-yl)amino)benzyl)piperazine-1- carboxylate (10 g, 24.1 mmol) in DMSO (200 mL) were added 2-aminopyridine-3-carbaldehyde (3.54 g, 29.0 mmol) and Na ₂ S ₂ O ₄ (12.6 g, 72.5 mmol) at 25 °C. The mixture was stirred at 100 °C for 14 hr. The reaction mixture was poured into H2O (500 mL). The mixture was extracted with CH2Cl2 (200 mL x 2). The combined organic layers were washed with brine (400 mL), dried over anhydrous Na ₂ SO ₄ , filtered, and concentrated. The residue was purified by silica gel flash chromatography (Eluent of 10~30% MeOH in CH2Cl2) to give 4-(4-(2-(2-Aminopyridin-3- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperazine-1-carbox yla (4.9 g, yield: 42%) as a red solid. MS: m/z = 486.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ J = 4.8, 1.2 Hz, 1 H), 8.20 (dd, J = 8.0, 1.2 Hz, 1 H), 7.99 (dd, J = 4.8, 2.0 Hz, 1 H), 7.43 - 7.48 (m, 2 H), 7.36 - 7.42 (m, 3 H), 7.16 (dd, J = 7.6, 1.6 Hz, 1 H), 7.00 (br s, 2 H), 6.38 (dd, J = 7.6, 4.8 Hz, 1 H), 3.56 (s, 2 H), 3.33 - 3.37 (m, 4 H), 2.32 - 2.38 (m, 4 H), 1.40 (s, 9 H). [00254] Step 5: 3-(3-(4-(Piperazin-1-ylmethyl)phenyl)-3H-imidazo[4,5-b]pyrid in-2-yl)pyridin- 2-amine [00255] To a solution of tert-butyl 4-(4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperazine-1-carboxylate (2 g, 4.12 mmol) in CH2Cl2 (10 mL) was added dropwise TFA (4.62 g, 40.5 mmol) at 25 °C, and the mixture was stirred at 25 °C for 3 hr. The reaction mixture was concentrated. The residue was poured into water (50 mL). The pH of the mixture was adjusted to about 8 by saturated NaHCO3 (aq). The resulting mixture was extracted with CH2Cl2 (100 mL x 3). The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated to give 3-(3-(4-(Piperazin-1-ylmethyl)phenyl)-3H-imidazo[4,5-b]pyrid in-2- yl)pyridin-2-amine (1.43 g, yield: 90%) as an off-white solid. The solid (100 mg) was triturated with EtOAc (3 mL) at 25 °C for 1 hr and filtered. The filter cake was collected to give 3-(3-(4- (Piperazin-1-ylmethyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl) pyridin-2-amine (Intermediate 42, 24.5 mg, yield: 90%). MS: m/z = 386.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide- d6 J = 4.0 Hz, 1H), 8.22 (d, J = 8.0 Hz, 1H), 8.00 (d, J = 3.2 Hz, 1H), 7.35 - 7.52 (m, 5H), 7.18 (d, J = 7.2 Hz, 1H), 7.00 (br s, 2H), 6.40 (dd, d, J = 7.8, 4.8 Hz, 1H), 3.63 (s, 2H), 3.16-3.01 (m, 4H), 2.63-2.48 (ms, 4H). WSGR Docket No.62619-716.601 [00256] Intermediate 43: 3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-3H-imidazo[4, 5- b]pyridin-2-yl)pyridin-2-amine [00257] Step 1: tert-Butyl (1-(4-nitrobenzyl) piperidin-4-yl) carbamate [00258] To a solution of 1-(bromomethyl)-4-nitro-benzene (108 g, 499 mmol) in ACN (1.5 L) were added K ₂ CO ₃ (149 g, 1.1 mol) and tert-butyl N-(4-piperidyl)carbamate (100 g, 499 mmol). The mixture was stirred at 25 °C for 16 hr. The reaction mixture was filtered. The filtrate was concentrated under reduced pressure to give tert-butyl (1-(4-nitrobenzyl) piperidin-4- yl)carbamate (167 g, crude) as a yellow solid, which was used in the next step without further purification. MS: m/z = 335.9 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d J = 8.8 Hz, 2H), 7.49 (d, J = 8.8 Hz, 2H), 4.44 (br s, 1H), 3.56 (s, 2H), 3.52 - 3.42 (m, 1H), 2.77 - 2.74 (m, 2H), 2.16 - 2.10 (m, 2H), 1.93 - 1.90 (m, 2H), 1.43 (s, 9H), 1.42 - 1.36 (m, 2H). [00259] Step 2: tert-Butyl (1-(4-aminobenzyl) piperidin-4-yl) carbamate [00260] To a solution of tert-butyl (1-(4-nitrobenzyl) piperidin-4-yl)carbamate (109 g, 325 mmol) in EtOH (500 mL) and H ₂ O (150 mL) were added Fe (91 g, 1.6 mol) and NH ₄ Cl (174 g, 3.3 mol). The mixture was stirred at 85°C for 2 hr. The reaction mixture was filtered. The filtrate was concentrated under pressure to remove most of the EtOH. The residue was diluted with H ₂ O (500 mL) and extracted with CH ₂ Cl ₂ (500 mL × 2). The combined organic layers were washed with brine (500 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure to give tert-butyl (1-(4-aminobenzyl) piperidin-4-yl) carbamate (80 g crude) as a yellow solid. MS: m/z = 306.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d J = 8.0 Hz, 2H), 6.64 (d, J = 8.0 Hz, 2H), 4.51 (br d, J = 6.0 Hz, 1H), 3.80 - 3.59 (m, 2H), 3.55 (s, 2H), 3.51 - 3.39 (m, 1H), 2.95 - 2.93 (m, 2H), 2.25 - 2.20 (m, 2H), 1.96 - 1.93 (m, 2H), 1.72 - 1.54 (m, 2H), 1.42 (s, 9H). [00261] Step 3: tert-Butyl (1-(4-((3-nitropyridin-2-yl) amino)benzyl)piperidin-4-yl)carbamate WSGR Docket No.62619-716.601 [00262] To a solution of tert-butyl (1-(4-aminobenzyl) piperidin-4-yl) carbamate (30 g, 98.2 mmol) in DMSO (500 mL) were added DIEA (38.1 g, 295 mmol) and 2-chloro-3-nitro-pyridine (18.7 g, 118 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was quenched with H2O (500 mL) at 20 °C and extracted with EtOAc (300 mL × 2). The combined organic layers were washed with brine (300 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. The crude was purified by silica gel flash chromatography (Eluent of 0~10% MeOH in CH2Cl2) to give tert-butyl (1-(4-((3-nitropyridin-2-yl) amino) benzyl) piperidin-4-yl) carbamate (30 g, yield: 71%) as a yellow solid. MS: m/z = 428.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d J = 8.0, 1.6 Hz, 1H), 8.47 (dd, J = 8.4, 1.6 Hz, 1H), 7.58 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 8.4 Hz, 2H), 6.81 (dd, J = 8.4, 4.4 Hz, 1H), 4.44 (br s, 1H), 3.47 (s, 2H), 3.44 - 3.34 (m, 1H), 2.82 - 2.79 (m, 2H), 2.13 - 2.05 (m, 2H), 1.93 - 1.89 (m, 2H), 1.43 (s, 9H), 1.39 - 1.37 (m, 2H). [00263] Step 4: tert-Butyl (1-(4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)carbamate [00264] To a solution of (12.5 g, 29.2 mmol) in DMSO (500 mL) were added Na2S2O4 (15.3 g, 87.7 mmol) and 2-aminopyridine-3-carbaldehyde (4.3 g, 35.1 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was quenched with H ₂ O (1000 mL) at 20 °C and extracted with EtOAc (1000 mL × 2). The combined organic layers were washed with brine (500 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude was purified by silica gel flash chromatography (Eluent of 0~10% MeOH in CH ₂ Cl ₂ ) to give tert- butyl (1-(4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl )benzyl)piperidin-4- yl)carbamate (5.5 g, yield: 38%) as a yellow solid. MS: m/z = 500.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d J = 8.0 Hz, 2H), 7.34 - 7.28 (m, 3H), 7.07 (dd, J = 8.0, 4.0 Hz, 1H), 6.62 (br s, 2H), 6.33 (dd, J = 7.6, 4.8 Hz, 1H), 4.46 (br d, J = 6.0 Hz, 1H), 3.56 (s, 2H), 3.49 - 3.47(m, 1H), 2.84 (br d, J = 11.2 Hz, 2H), 2.14 (t, J = 12.0 Hz, 2H), 1.93 (br d, J = 11.2 Hz, 2H), 1.45 (s, 9H), 1.51-1.38 (m, 2H). [00265] Step 5.3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-3H-imidazo[ 4,5-b]pyridin-2- yl)pyridin-2-amine [00266] A solution of tert-butyl (1-(4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)carbamate (2.0 g, 4.0 mmol) in HCl/1,4-dioxane (4M, 20 mL) was stirred at 25 °C for 1 hr. The reaction mixture was concentrated under reduced pressure. The residue was quenched with NaHCO ₃ (30 mL) at 20°C, then MeOH was added, filtered, and the filtrate after freeze-dried to give 3-(3-(4-((4-aminopiperidin-1-yl)methyl)phenyl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (Intermediate 43, 1.45 g, yield: 91%) as a yellow WSGR Docket No.62619-716.601 solid. MS: m/z = 400.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 1H), 8.19 (dd, J = 8.0, 4.0 Hz, 1H), 7.99 – 7.97 (m, 1H), 7.47 - 7.32 (m, 5H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 7.01 (br s, 2H), 6.36 (dd, J = 6.8, 4.0 Hz, 1H), 3.50 (s, 2H), 3.27 – 3.23(m, 1H), 2.75 (br d, J = 10.8 Hz, 2H), 2.00 (t, J = 10.8 Hz, 2H), 1.72 ( d, J = 10.8 Hz, 2H), 1.39 -1.31 (m, 2H). [00267] Intermediate 44: 2-Methoxyacrylic acid [00268] To a solution of t-BuOK (5.40 g, 48.1 mmol) in THF (80 mL) was added 2- oxopropanoic acid (1.25 g, 14.2 mmol) in THF (45 mL) at -70 °C under N2. After the mixture was stirred at -70 °C for 15 min, a solution of HMPA (20.5 g, 114 mmol) in THF (80 mL) was added. n-BuLi (2.5 M, 22.9 mL) was added to the resulting mixture after stirring at -70 °C for another 30 min. After the reaction mixture stirred at -70 °C for 1 hr, Me2SO4 (3.56 g, 28.2 mmol) was added. After stirring at -70 °C for 15 min, the reaction mixture was warmed to 25 °C and stirred at 25 °C for 12 hr. The reaction mixture was quenched with H2O (20 mL) and extracted with H ₂ O (20 mL). The combined aqueous phases were washed with CH ₂ Cl ₂ (20 mL x 2), acidified to adjust pH to 2-3 with 10% HCl aqueous solution, and extracted with EtOAc (30 mL x 3). The combined organic layers were washed with brine (20 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. 2-Methoxyacrylic acid (Intermediate 44, 1 g) was obtained as a yellow oil, which was used in the next step without further purification. ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 J = 2.0 Hz, 1H), 4.68 (d, J = 2.0 Hz, 1H), 3.54 (s, 3H). [00269] Intermediate 45: tert-Butyl 4-(4-(2-(2-aminopyridin-3-yl)-5-chloro-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazine-1-carboxylate [00270] To a solution of tert-butyl 4-(4-((6-chloro-3-nitropyridin-2-yl)amino)benzyl)piperazine- 1-carboxylate (refer to Intermediate 2 for detail procedures, 21 g, 46.9 mmol) in DMSO (300 mL) were added 2-aminonicotinaldehyde (6.87 g, 56.4 mmol) and Na ₂ S ₂ O ₄ (28.8 g, 141 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was quenched with H2O (300 WSGR Docket No.62619-716.601 mL) at 25°C and extracted with CH2Cl2 (500 mL x 2). The combined organic layers were washed with H ₂ O (1000 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purification by silica gel flash chromatography (Eluent of 1 ~ 8% MeOH in CH2Cl2), tert-butyl 4-(4-(2-(2-aminopyridin-3-yl)-5-chloro-3H-imidazo[4,5-b]pyri din-3- yl)benzyl)piperazine-1-carboxylate (Intermediate 45, 6.3 g, yield: 25%) was obtained as a yellow solid. MS: m/z = 520.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d J = 4.8, 2.0 Hz, 1H), 8.02 (d, J = 8.4 Hz, 1H), 7.49 (d, J = 8.4 Hz, 2H), 7.31 (dd, J = 8.4, 2.8 Hz, 3H), 7.02 (dd, J = 8.0, 2.0 Hz, 1H), 6.62 (br s, 2H), 6.33 (dd, J = 8.0, 4.8 Hz, 1H), 3.61 (s, 2H), 3.50 - 3.45 (m, 4H), 2.49 - 2.43 (m, 4H), 1.47 (s, 9H). [00271] Intermediate 46: 3-(5-Cyclopropyl-3-(4-(piperazin-1-ylmethyl)phenyl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00272] Step 1: tert-Butyl 4-(4-(2-(2-aminopyridin-3-yl)-5-cyclopropyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazine-1-carboxylate [00273] 2O (0.1 mL) were added K3PO4 Pd(dppf)Cl ₂ ·CH ₂ Cl ₂ reaction was concentrated under reduced pressure. The residue was purified by prep-TLC (MeOH in CH2Cl2 = 10%) to give tert-butyl 4-(4-(2-(2-aminopyridin-3-yl)-5-cyclopropyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazine-1-carboxylate (19.0 mg, yield: 19%) as an off white solid. MS: m/z = 526.3 [M + H] ⁺ . [00274] Step 2: 3-(5-Cyclopropyl-3-(4-(piperazin-1-ylmethyl)phenyl)-3H-imida zo[4,5- b]pyridin-2-yl)pyridin-2-amine [00275] To a solution of tert-butyl 4-(4-(2-(2-aminopyridin-3-yl)-5-cyclopropyl-3H- imidazo[4,5-b dioxane (1 mL) was added HCl/1,4-dioxane (4 M, 1 mL). The mixture was stirred at 100 °C for 2 hr. The pH of the mixture was adjusted to = 7 with saturated NaHCO ₃ at 25 °C. The mixture was concentrated under reduced pressure. After purification by prep-TLC (MeOH in CH2Cl2 = 10%), 3-(5-cyclopropyl-3-(4-(piperazin-1-ylmethyl)phenyl)-3H-imida zo[4,5-b]pyridin-2- yl)pyridin-2-amine (Intermediate 46, 4.7 mg, yield: 25%) was obtained as an off white solid. WSGR Docket No.62619-716.601 MS: m/z = 426.0 [M + H] ⁺ . ¹ H NMR (400MHz, Methanol-d4 J = 8.4 Hz, 2H), 7.36 (d, J = 8.0 Hz, 2H), 7.32 - 7.20 (m, 2H), 6.47 (dd, J = 7.6, 4.8 Hz, 1H), 3.68 (s, 2H), 3.19 (t, J = 5.2 Hz, 4H), 2.73 -2.64 (m, 4H), 2.23 - 2.12 (m, 1H), 0.99 - 0.88 (m, 4H). [00276] Intermediate 47: 3-(5-(Cyclohex-1-en-1-yl)-3-(4-(piperazin-1-ylmethyl)phenyl) -3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00277] Intermediate 47 was prepared in a manner similar to Intermediate 46. MS: m/z = 466.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ J = 8.4 Hz, 1H), 8.01 (dd, J = 6.4, 1.6 Hz, 1H), 7.90 (d, J = 8.4 Hz, 2H), 7.85 (dd, J = 7.6, 1.4 Hz, 1H), 7.70 - 7.62 (m, 3H), 6.92 (dd, J = 7.6, 6.4 Hz, 1H), 6.75 - 6.69 (m, 1H), 4.62 (s, 2H), 3.69 - 3.68 (m, 7H), 3.60 - 3.59 (m, 1H), 2.56 - 2.47 (m, 2H), 2.30 - 2.21 (m, 2H), 1.81 - 1.64 (m, 4H). [00278] Intermediate 48: 3-(5-(3,6-Dihydro-2H-pyran-4-yl)-3-(4-(piperazin-1-ylmethyl) phenyl)- 3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00279] Intermediate 48 was prepared in a manner similar to Intermediate 46. MS: m/z = 468.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4 J = 8.4 Hz, 1H), 8.01 (dd, J = 6.4, 1.2 Hz, 1H), 7.93 - 7.83 (m, 3H), 7.75 - 7.62 (m, 3H), 6.96 - 6.87 (m, 1H), 6.75 - 6.74 (m, 1H), 4.62 (s, 2H), 4.39 - 4.29 (m, 2H), 3.90 (t, J = 5.2 Hz, 2H), 3.69 - 3.68 (m, 8H), 2.68-2.57 (m, 2H). [00280] Intermediate 49: 3-(5-Morpholino-3-(4-(piperazin-1-ylmethyl)phenyl)-3H-imidaz o[4,5- b]pyridin-2-yl)pyridin-2-amine WSGR Docket No.62619-716.601 [00281] Step 1: tert-Butyl 4-(4-((6-morpholino-3-nitropyridin-2-yl)amino)benzyl)piperaz ine-1- carboxylate [00282] To a solution of tert-butyl 4-(4-((6-chloro-3-nitropyridin-2-yl)amino)benzyl)piperazine- 1-carboxylate (refer to Intermediate 2 for detail procedures, 300 mg, 670 µmol) and morpholine (117 mg, 1.34 mmol) in CH ₃ CN (4 mL) was added DIEA (173 mg, 1.34 mmol). The mixture was stirred at 90 °C for 2 hr. The reaction mixture was quenched with H2O (10 mL) at 25 °C and extracted with CH2Cl2 (15 mL x 2). The combined organic layers were washed with brine (15 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give tert-butyl 4-(4-((6-morpholino-3-nitropyridin-2-yl)amino)benzyl)piperaz ine-1-carboxylate (330 mg, yield: 93%) as a yellow solid. MS: m/z = 499.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d 10.71 (s, 1H), 8.32 (d, J = 9.2 Hz, 1H), 7.53 (d, J = 8.0 Hz, 2H), 7.30 (d, J = 8.0 Hz, 2H), 6.13 (d, J = 9.6 Hz, 1H), 3.79 - 3.75 (m, 4H), 3.73 - 3.67 (m, 4H), 3.50 (s, 2H), 3.46 - 3.40 (m, 4H), 2.44 - 2.35 (m, 4H), 1.45 (s, 9H). [00283] Step 2: tert-Butyl 4-(4-(2-(2-aminopyridin-3-yl)-5-morpholino-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazine-1-carboxylate [00284] To a solution of tert-butyl 4-(4-((6-morpholino-3-nitropyridin-2- yl)amino)benzyl)piperazine-1-carboxylate (330 mg, 662 µmol) in DMSO (10 mL) were added 2-aminonicotinaldehyde (97 mg, 794 µmol) and Na2S2O4 (542 mg, 2.65 mmol). The mixture was stirred at 100 °C for 2 hr. The reaction mixture was quenched with H2O (20 mL) at 25 °C and extracted with CH ₂ Cl ₂ (50 mL x 3). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give the crude product. The crude was purified by silica gel flash chromatography (Eluent of 1 ~ 5% MeOH in CH ₂ Cl ₂ ) to give tert-butyl 4-(4-(2-(2-aminopyridin-3-yl)-5-morpholino-3H-imidazo[4,5- WSGR Docket No.62619-716.601 b]pyridin-3-yl)benzyl)piperazine-1-carboxylate (270 mg, yield: 68%) as a yellow solid. MS: m/z = 571.2 [M + H] ⁺ . [00285] Step 3: 3-(5-Morpholino-3-(4-(piperazin-1-ylmethyl)phenyl)-3H-imidaz o[4,5-b]pyridin- 2-yl)pyridin-2-amine [00286] To a solution of tert-butyl 4-(4-(2-(2-aminopyridin-3-yl)-5-morpholino-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazine-1-carboxylate (270 mg, 473 µmol) in 1,4-dioxane 16 hr. The reaction was concentrated under reduced pressure to give 3-(5-morpholino-3-(4- (piperazin-1-ylmethyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl) pyridin-2-amine (Intermediate 49, 240 mg, HCl salt, yield: 93%) as a yellow solid. MS: m/z = 471.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ J =8.4, 3.2 Hz, 2H), 7.14 - 7.02 (m, 1H), 7.01 - 6.90 (m, 1H), 4.66 - 4.59 (m, 2H), 3.82 - 3.77 (m, 4H), 3.73 - 3.69 (m, 6H), 3.68 (s, 2H), 3.60 - 3.55 (m, 4H). [00287] Intermediate 50: 3-(2-(2-Aminopyridin-3-yl)-3-(4-(piperazin-1-ylmethyl)phenyl )-3H- imidazo[4,5-b]pyridin-5-yl)benzonitrile [00288] Step 1: tert-Butyl 4-(4-(2-(2-aminopyridin-3-yl)-5-(3-cyanophenyl)-3H-imidazo[4 ,5- b]pyridin-3-yl)benzyl)piperazine-1-carboxylate [00289] 2CO3 (414 mg, 1.27 mmol), and Pd(dppf)Cl2 dioxane (5 mL) and H ₂ O (1 mL) was degassed and purged with N ₂ three times. The mixture was stirred at 100 °C for 16 hr under N2 atmosphere. The reaction mixture was filtered at 25°C, diluted with H ₂ O (20 mL), and extracted with CH ₂ Cl ₂ (20 mL x 3). The combined organic layers were washed with brine (30 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purification by silica gel flash chromatography (Eluent of 0 ~ 30% EtOAc in petroleum ether), tert-butyl 4-(4-(2-(2-aminopyridin-3-yl)-5-(3-cyanophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazine-1-carboxylate (240 mg, yield: 97%) was obtained as a brown solid. MS: m/z = 587.4 [M + H] ⁺ . WSGR Docket No.62619-716.601 [00290] Step 2: 3-(2-(2-Aminopyridin-3-yl)-3-(4-(piperazin-1-ylmethyl)phenyl )-3H- imidazo[4,5-b]pyridin-5-yl)benzonitrile [00291] To a solution of tert-butyl 4-(4-(2-(2-aminopyridin-3-yl)-5-(3-cyanophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazine-1-carboxylate (240 mg, 409 µmol) in 1,4-dioxane for 16 hr. The reaction mixture was filtered. The collected solid was washed with 1,4-dioxane (2 mL x 2) and dried in vacuo to give 3-(2-(2-aminopyridin-3-yl)-3-(4-(piperazin-1- ylmethyl)phenyl)-3H-imidazo[4,5-b]pyridin-5-yl)benzonitrile (Intermediate 50, 203 mg HCl salt, yield: 95%) as a yellow solid. MS: m/z = 487.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol- d4 J = 8.4 Hz, 1H), 8.03 (d, J = 5.6 Hz, 1H), 7.96 (d, J = 8.4 Hz, 2H), 7.90 (d, J = 7.6 Hz, 1H), 7.79 - 7.73 (m, 3H), 7.68 - 7.63 (m, 1H), 6.96 - 6.90 (m, 1H), 3.70 - 3.68 (m, 6H), 3.67 – 3.65 (m, 4H). [00292] Intermediate 51: 4-(2-(2-Aminopyridin-3-yl)-3-(4-(piperazin-1-ylmethyl)phenyl )-3H- imidazo[4,5-b]pyridin-5-yl)benzonitrile [00293] Intermediate 51 was prepared in a manner similar to Intermediate 50. MS: m/z = 487.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ J = 8.4 Hz, 1H), 8.25 (d, J = 8.4 Hz, 2H), 8.13 (d, J = 8.4 Hz, 1H), 8.04 (d, J = 5.6 Hz, 1H), 7.95 (d, J = 7.6 Hz, 2H), 7.89 (d, J = 7.2 Hz, 1H), 7.81 (d, J = 8.4 Hz, 2H), 7.74 (d, J = 7.6 Hz, 2H), 6.93 (t, J = 6.8 Hz, 1H), 3.71 - 3.70 (m, 6H), 3.68 - 3.64 (m, 4H). [00294] Intermediate 52: 3-(5-(3-Fluorophenyl)-3-(4-(piperazin-1-ylmethyl)phenyl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine WSGR Docket No.62619-716.601 [00295] Intermediate 52 was prepared in a manner silimar to Intermediate 50. MS: m/z = 480.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ J = 8.4 Hz, 1H), 8.08 - 8.01 (m, 2H), 7.98 - 7.86 (m, 4H), 7.81 - 7.71 (m, 3H), 7.52 - 7.42 (m, 1H), 7.18 - 7.12 (m, 1H), 6.98 – 6.85 (m, 1H), 3.69 - 3.67 (m, 4H), 3.35 (s, 2H), 3.34 - 3.31 (m, 4H). ¹⁹ F NMR (400 MHz, Methanol- d ₄ [00296] Intermediate 53: 6-(2-(2-Aminopyridin-3-yl)-3-(4-(piperazin-1-ylmethyl)phenyl )-3H- imidazo[4,5-b]pyridin-5-yl)pyridin-2(1H)-one [00297] Intermediate 53 was prepared in a manner similar to Intermediate 50. MS: m/z = 479.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 J = 8.4 Hz, 1H), 8.16 (d, J = 8.4 Hz, 1H), 8.01 (dd, J = 4.8, 2.0 Hz, 1H), 7.60 (dd, J = 8.8, 6.8 Hz, 1H), 7.52 - 7.41 (m, 5H), 7.20 - 7.14 (m, 2H), 7.02 (br s, 2H), 6.46 (d, J = 8.8 Hz, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.53 (s, 2H), 2.73 - 2.69 (m, 4H), 2.36 - 2.30 (m, 4H). [00298] Intermediate 54: 5-(2-(2-Aminopyridin-3-yl)-3-(4-(piperazin-1-ylmethyl)phenyl )-3H- imidazo[4,5-b]pyridin-5-yl)pyridin-2(1H)-one [00299] Intermediate 54 was prepared in a manner similar to Intermediate 50. MS: m/z = 479.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4 J = 9.2 Hz, 1H), 8.61 (s, 1H), 8.37 (d, J = 8.4 Hz, 1H), 8.01 - 8.07 (m, 2H), 7.95 (d, J = 8.0 Hz, 2H), 7.90 (d, J = 7.2 Hz, 1H), 7.73 (d, J = 7.6 Hz, 2H), 7.08 (d, J = 9.2 Hz, 1H), 6.94 (t, J = 6.8 Hz, 1H), 4.67 (s, 2H), 3.82 - 3.64 (m, 8H). [00300] Intermediate 55: 3-(5-(3-Chlorophenyl)-3-(4-(piperazin-1-ylmethyl)phenyl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine WSGR Docket No.62619-716.601 [00301] Intermediate 55 was prepared in a manner similar to Intermediate 50. MS: m/z = 496.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ J = 8.4 Hz, 1H), 8.04 (s, 1H), 8.01 - 7.92 (m, 3H), 7.55 (d, J = 8.0 Hz, 2H), 7.45 (d, J = 8.4 Hz, 2H), 7.43 - 7.33 (m, 3H), 6.48 (dd, J = 7.6, 5.2 Hz, 1H), 3.64 (s, 2H), 2.92 (t, J = 5.2 Hz, 4H), 2.50 - 2.58 (m, 4H). [00302] Intermediate 56: 4-(2-(2-Aminopyridin-3-yl)-3-(4-(piperazin-1-ylmethyl)phenyl )-3H- imidazo[4,5-b]pyridin-5-yl)-1-methylpyridin-2(1H)-one [00303] Intermediate 56 was prepared in a manner similar to Intermediate 50. MS: m/z = 493.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ J = 8.0 Hz, 1H), 8.17 (d, J = 8.4 Hz, 1H), 8.09 - 8.02 (m, 1H), 7.97 - 7.90 (m, 4H), 7.74 (d, J = 8.4 Hz, 2H), 7.49 (s, 1H), 7.38 - 7.37 (m, 1H), 6.96 - 6.92 (m, 1H), 3.74 - 3.66 (m, 10H), 3.30 (s, 3H). [00304] Intermediate 57: 5-(2-(2-Aminopyridin-3-yl)-3-(4-(piperazin-1-ylmethyl)phenyl )-3H- imidazo[4,5-b]pyridin-5-yl)-1-methylpyridin-2(1H)-one [00305] Intermediate 57 was prepared in a manner similar to Intermediate 50. MS: m/z = 493.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4 J = 1.6 Hz, 1H), 8.34 - 8.26 (m, 2H), 8.02 (d, J = 6.0 Hz, 1H), 7.96 - 7.90 (m, 3H), 7.86 (d, J = 7.6 Hz, 1H), 7.72 (d, J = 8.4 Hz, 2H), 6.91 (t, J = 6.8 Hz, 1H), 6.66 (d, J = 9.2 Hz, 1H), 3.74 - 3.66 (m, 10H), 3.60 (s, 3H). WSGR Docket No.62619-716.601 [00306] Intermediate 58: tert-Butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-chloro-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)carbamate [00307] A mixture of tert-butyl (1-(4-((6-chloro-3-nitropyridin-2-yl)amino)benzyl)piperidin- 4- yl)carbamate (refer to Intermediate 3 for detail procedures, 13.0 g, 28.0 mmol), 2- aminopyridine-3-carbaldehyde (4.12 g, 33.8 mmol), and Na2S2O4 (23.1 g, 112 mmol) in DMSO (500 mL) was degassed and purged with N ₂ three times. The mixture was stirred at 100 °C for 16 hr under N ₂ atmosphere. The reaction mixture was diluted with water (500 mL) and extracted with EtOAc (500 mL × 3). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 0 ~ 8% MeOH in CH ₂ Cl ₂ ) to give tert-butyl (1-(4-(2-(2- aminopyridin-3-yl)-5-chloro-3H-imidazo[4,5-b]pyridin-3-yl)be nzyl)piperidin-4-yl)carbamate (Intermediate 58, 4.8 g, yield: 28%) as a yellow solid. MS: m/z = 534.3 [M + H] ⁺ . [00308] Intermediate 59: 3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-5-cyclopropyl -3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00309] Step 1: tert-Butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-cyclopropyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)carbamate [00310] 1.1 mmol), t ₂ O (2 mL) and 1,4-dioxane (8 mL) was degassed and purged with N2 three times. The mixture was stirred at 100 °C for 16 hr under N ₂ atmosphere. The reaction mixture was quenched with H ₂ O (30 mL) at 25 °C and extracted with EtOAc (30 mL × 2). The combined organic layers were washed with brine (30 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude was purified by silica gel flash chromatography (Eluent of 0~100% EtOAc in petroleum ether) to give tert-butyl(1-(4-(2-(2-aminopyridin-3-yl)-5-cyclopropyl-3H- WSGR Docket No.62619-716.601 imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)carbamate (120 mg, yield:40%) as a yellow solid. MS: m/z = 540.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d J = 4.8, 1.6 Hz, 1H), 7.92 (d, J = 8.4 Hz, 1H), 7.48 - 7.43 (m, 2H), 7.31 – 7.28 (m, 2H), 7.12 (d, J = 8.4 Hz, 1H), 7.02 (dd, J = 7.6, 1.6 Hz, 1H), 6.52 (br s, 2H), 6.33 (dd, J = 7.6, 4.8 Hz, 1H), 4.52 - 4.41 (m, 1H), 3.68 - 3.51 (m, 3H), 2.98 - 2.85 (m, 2H), 2.30 - 2.17 (m, 2H), 2.12 - 2.11 (m, 1H), 2.01 - 1.95 (m, 2H), 1.45 - 1.43 (m, 11H), 0.96 – 0.92 (m, 4H). [00311] Step 2: 3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-5-cyclopropyl -3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00312] A solution of tert-butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-cyclopropyl-3H-imidazo[4,5- 3 mL) was stirred at 25 °C for 1 hr. The mixture was concentrated under reduced pressure to give 3-(3-(4-((4-aminopiperidin-1-yl)methyl)phenyl)-5-cyclopropyl -3H-imidazo[4,5-b]pyridin- 2-yl)pyridin-2-amine (Intermediate 59, 110 mg HCl salt, yield: 96%) as a light yellow solid. MS: m/z = 440.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ (m, 1H), 7.98 -7.85 (m, 3H), 7.61 (d, J = 7.2 Hz, 2H), 7.41 - 7.30 (m, 1H), 6.96 - 6.79 (m, 1H), 4.48 (s, 2H), 3.68 (d, J = 11.6 Hz, 2H), 3.60 - 3.65 (m, 2H), 3.29 - 3.23 (m, 1H), 2.31 (d, J = 12.8 Hz, 2H), 2.26 - 2.03 (m, 3H), 1.07 - 0.88 (m, 4H). [00313] Intermediate 60: 3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-5-(3,6-dihydr o-2H- pyran-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00314] Step 1: tert-Butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-(3,6-dihydro-2H-pyran-4-yl) -3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)carbamate [00315] A mixture of Intermediate 58 (800 mg, 1.5 mmol), 2-(3,6-dihydro-2H-pyran-4-yl)- 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (629 mg, 3 mmol), Pd(dppf)Cl ₂ Cs2CO3 (976 mg, 3 mmol) in 1,4-dioxane (10 mL) and H2O (2 mL) was degassed and purged with N2 three times. The mixture was stirred at 100 °C for 6 hr under N2 atmosphere and concentrated under reduced pressure. After purification by silica gel flash chromatography (MeOH in CH2Cl2 = 0% to 7%), tert-butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-(3,6-dihydro-2H- WSGR Docket No.62619-716.601 pyran-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4 -yl)carbamate (760 mg, yield: 78%) was obtained as a yellow solid. MS: m/z = 582.3 [M + H] ⁺ . [00316] Step 2: 3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-5-(3,6-dihydr o-2H-pyran-4- yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00317] To a solution of tert-butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-(3,6-dihydro-2H-pyran-4- yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)carb amate CH2Cl2 (4 mL) was added HCl in 1,4-dioxane (4 M, 4 mL). The mixture was stirred at 25 °C for 0.5 hr. The reaction mixture was concentrated under reduced pressure. The residue was diluted with H2O (100 mL) and washed with EtOAc (150 mL). The pH of the aqueous phase was adjusted to 8 with saturated NaHCO3. The aqueous was extracted with EtOAc (50 mL x 3). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purification by silica gel flash chromatography (EtOAc in petroleum ether = 0% to 100%), 3-(3-(4-((4-aminopiperidin-1-yl)methyl)phenyl)-5- (3,6-dihydro-2H-pyran-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)py ridin-2-amine (Intermediate 60, 170 mg, yield: 60%) was obtained as a yellow solid. MS: m/z = 482.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ J = 8.4 Hz, 1H), 7.98 (dd, J = 4.8, 1.6 Hz, 1H), 7.58 (d, J = 8.4 Hz, 1H), 7.44 - 7.40 (m, 2H), 7.38 - 7.34 (m, 2H), 7.11 (dd, J = 7.6, 1.2 Hz, 1H), 7.01 (br s, 2H), 6.70 - 6.65 (m, 1H), 6.35 (dd, J = 7.6, 4.8 Hz, 1H), 4.25 (d, J = 2.4 Hz, 2H), 3.79 (t, J = 5.6 Hz, 2H), 3.56 - 3.48 (m, 3H), 2.74 (d, J = 11.2 Hz, 2H), 2.60 - 2.51 (m, 4H), 2.02 - 1.95 (m, 2H), 1.72 - 1.63 (m, 2H), 1.37 - 1.20 (m, 2H). [00318] Intermediate 61: 3-(2-(2-Aminopyridin-3-yl)-3-(4-(piperazin-1-ylmethyl)phenyl )-3H- imidazo[4,5-b]pyridin-5-yl)pyridin-2(1H)-one [00319] Intermediate 61 was prepared in a manner similar to Intermediate 60. MS: m/z = 479.2 [M + H] ⁺ . [00320] Intermediate 62: 3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-5-(3-fluoroph enyl)- 3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine WSGR Docket No.62619-716.601 [00321] Intermediate 62 was prepared in a manner similar to Intermediate 60. MS: m/z = 494.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 4H), 8.18 - 8.10 (m, 2H), 7.94 (d, J = 8.0 Hz, 1H), 7.91 - 7.81 (m, 4H), 7.72 - 7.64 (m, 2H), 7.57 - 7.51 (m, 1H), 7.31 - 7.20 (m, 2H), 7.18 - 7.12 (m, 1H), 6.94 - 6.85 (m, 1H), 4.37 - 4.34 (m, 2H), 3.57 (s, 2H), 3.33 - 3.30 m, 1H), 3.12 - 3.02 (m, 2H), 2.22 - 2.14 (m, 2H), 2.09 - 1.95 (m, 2H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d6 [00322] Intermediate 63: 3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-5-(3-chloroph enyl)- 3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00323] Intermediate 63 was prepared in a manner similar to Intermediate 60. MS: m/z = 510.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ J = 8.4 Hz, 1H), 8.07 - 8.03 (m, 1H), 7.99 - 7.96 (m, 2H), 7.55(d, J = 8.4 Hz, 2H), 7.48 - 7.31 (m, 6H), 6.47 (dd, J = 7.6, 4.8 Hz, 1H), 3.64 (s, 2H), 2.98 - 2.93 (m, 2H), 2.80 - 2.72 (m, 1H), 2.18 - 2.12 (m, 2H), 1.91 - 1.85 (m, 2H), 1.55 - 1.48 (m, 2H). [00324] Intermediate 64: 4-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-2-(2-aminopyr idin-3- yl)-3H-imidazo[4,5-b]pyridin-5-yl)-1-methylpyridin-2(1H)-one [00325] Intermediate 64 was prepared in a manner similar to Intermediate 60. MS: m/z = 507.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ J = 8.4 Hz, 1H), 8.10 (d, J = 8.4 Hz, 1H), 8.03 (dd, J = 5.6, 1.2 Hz, 1H), 7.90 - 7.84 (m, 3H), 7.70 (d, J = 7.2 Hz, 1H), 7.71 (d, J = 8.0 WSGR Docket No.62619-716.601 Hz, 2H), 7.26 (d, J = 1.6 Hz, 1H), 7.11 (dd, J = 6.8, 2.0 Hz, 1H), 6.88 (dd, J = 7.6, 5.6 Hz, 1H), 3.69 - 3.67 (m, 6H), 3.62 (s, 3H), 3.58 - 3.53 (m, 1H), 2.36 (d, J = 13.2 Hz, 2H), 2.14 - 2.02 (m, 2H). [00326] Intermediate 65: 5-(3-(4-((4-aminopiperidin-1-yl)methyl)phenyl)-2-(2-aminopyr idin-3- yl)-3H-imidazo[4,5-b]pyridin-5-yl)pyridin-2(1H)-one [00327] Intermediate 65 was prepared in a manner similar to Intermediate 60. MS: m/z = 493.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ J = 8.4 Hz, 1H), 8.05 - 8.01 (m, 1H), 7.97 (d, J = 8.4 Hz, 1H), 7.92 - 7.86 (m, 3H), 7.73 - 7.69 (m, 2H), 6.92 - 6.84 (m, 2H), 3.73 - 3.67 (m, 2H), 3.67 – 3.65 (m, 1H), 3.62 - 3.57 (m, 2H), 3.38 – 3.34 (m, 2H), 2.35 – 2.30 (m, 2H), 2.21 - 2.13 (m, 2H). [00328] Intermediate 66: 6-(3-(4-((4-aminopiperidin-1-yl)methyl)phenyl)-2-(2-aminopyr idin-3- yl)-3H-imidazo[4,5-b]pyridin-5-yl)pyridin-2(1H)-one [00329] Intermediate 66 was prepared in a manner similar to Intermediate 60. MS: m/z = 493.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ J = 8.4 Hz, 1H), 8.25 (d, J = 8.0 Hz, 1H), 8.08 - 7.98 (m, 2H), 7.96 - 7.89 (m, 3H), 7.78 – 7.72 (m, 2H), 7.50 – 7.58 (m, 1H), 6.94 - 6.82 (m, 2H), 3.76 - 3.68 (m, 2H), 3.66 (s, 2H), 3.61 - 3.56 (m, 1H), 3.38 – 3.32 (m, 2H), 2.36 – 2.29 (m, 2H), 2.21 - 2.08 (m, 2H). [00330] Intermediate 67: 3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-2-(2-aminopyr idin- 3-yl)-3H-imidazo[4,5-b]pyridin-5-yl)pyridin-2(1H)-one WSGR Docket No.62619-716.601 [00331] Intermediate 67 was prepared in a manner similar to Intermediate 60. MS: m/z = 493.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4 J = 8.4 Hz, 1H), 8.43 (d, J = 8.0 Hz, 1H), 8.05 - 8.03 (m, 1H), 7.96 - 7.88 (m, 3H), 7.80 (d, J = 5.2 Hz, 1H), 7.75 - 7.74 (m, 2H), 6.94 - 6.84 (m, 2H), 4.52 (s, 2H), 3.78 - 3.62 (m, 3H), 3.61 - 3.49 (m, 2H), 2.35 - 2.28 (m, 2H), 2.20 - 2.10 (m, 2H). [00332] Intermediate 68: 3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-6-phenyl-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00333] Step 1: tert-butyl (1-(4-((5-bromo-3-nitropyridin-2-yl)amino)benzyl)piperidin-4 - yl)carbamate [00334] A mixture of 5-bromo-2-chloro-3-nitro-pyridine (17.1 g, 72 mmol), tert-butyl N-[1-[(4- aminophenyl)methyl]-4-piperidyl]carbamate (22 g, 72 mmol), DIEA (27.9 g, 216 mmol) in DMSO (200 mL) was stirred at 80 °C for 16 hr. After cooling to 25 °C, the mixture was extracted with EtOAc (250 mL x 3). The combined organic layers were washed with brine (200 mL x 2), dried over anhydrous Na ₂ SO ₄ , filtered, and concentrated to give tert-butyl (1-(4-((5- bromo-3-nitropyridin-2-yl)amino)benzyl)piperidin-4-yl)carbam ate crude product (32g) as black brown solid. MS: m/z = 506.9, 507.9 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d 1H), 8.64 (d, J = 2.0 Hz, 1H), 8.49 (d, J = 2.4 Hz, 1H), 7.53 (d, J = 8.4 Hz, 2H), 7.33 (d, J = 8.4 Hz, 2H), 4.34 (d, J = 3.2 Hz, 1H), 3.48 (s, 2H), 3.46-3.35 (m, 1H), 2.82 (br d, J = 12.0 Hz, 2H), 2.10 (t, J = 10.8 Hz, 2H), 1.91 (br d, J = 11.2 Hz, 2H), 1.44 (s, 9H). WSGR Docket No.62619-716.601 [00335] Step 2: tert-Butyl (1-(4-((3-nitro-5-phenylpyridin-2-yl)amino)benzyl)piperidin- 4- yl)carbamate [00336] A mixture of tert-butyl (1-(4-((5-bromo-3-nitropyridin-2-yl)amino)benzyl)piperidin-4 - yl)carbamate (20 g, 39.5 mmol), phenylboronic acid (4.8 g, 39.5 mmol), K2CO3 (16.4 g, 118.5 mmol), Pd(dppf)Cl ₂ (1.4 g, 2.0 mmol) in 1,4-dioxane (250 mL) and H ₂ O (50 mL) was degassed and purged with N2 three times. The mixture was stirred at 80 °C for 16 hr under N2 atmosphere. After cooling to 25 °C, the reaction mixture was filtered, diluted with H2O (100 mL) and EtOAc (450 mL). The organic phase was separated, washed with brine (100 mL x 3), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 3~4% MeOH in CH2Cl2) to give tert-butyl (1-(4- ((3-nitro-5-phenylpyridin-2-yl)amino)benzyl)piperidin-4-yl)c arbamate (8.6 g, yield: 43%) as a red brown soild. MS: m/z = 504.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d 1H), 8.75 (dd, J = 10.0, 2.0 Hz, 2H), 7.62 (d, J = 8.0, Hz, 2H), 7.57 (d, J = 7.2, Hz, 2H), 7.49 (dd, J = 8.0, 8.0 Hz, 2H), 7.43 - 7.37 (m, 3H), 4.43 (br s, 1H), 3.50 (br s, 2H), 3.49-3.41 (m, 1H), 2.85 - 2.81 (m, 2H), 2.15 - 2.08 (m, 2H), 1.94 - 1.91 (m, 2H), 1.51-1.45 (m, 2H), 1.44 (s, 9H). [00337] Step 3: tert-Butyl (1-(4-(2-(2-aminopyridin-3-yl)-6-phenyl-3H-imidazo[4,5-b]pyr idin- 3-yl)benzyl)piperidin-4-yl)carbamate [00338] A mixture of tert-butyl (1-(4-((3-nitro-5-phenylpyridin-2-yl)amino)benzyl)piperidin- 4- yl)carbamate (2.2 g, 4.4 mmol), 2-aminopyridine-3-carbaldehyde (694 mg, 5.7 mmol), Na2S2O4 (1.5 g, 8.7 mmol) in DMSO (100 mL) was degassed and purged with N ₂ three times, The mixture was stirred at 100 °C for 16 hr under N2 atmosphere. After cooling to 25 °C, the reaction mixture was filtered, diluted with H2O (30 mL) and extracted with EtOAc (45 mL). The organic phase was separated, washed with brine (10 mL x 3), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 5~6% EtOAc in petroleum ether) to give tert-butyl (1-(4-(2-(2- aminopyridin-3-yl)-6-phenyl-3H-imidazo[4,5-b]pyridin-3-yl)be nzyl)piperidin-4-yl)carbamate (700 mg, yield: 28%) as a black brown soild. MS: m/z = 576.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d J = 2.0 Hz, 1H), 8.27 (d, J = 2.0 Hz, 1H), 8.07 (dd, J = 5.2, 2.0 Hz, 1H), 7.67 - 7.62 (m, 2H), 7.54 - 7.47 (m, 4H), 7.44 - 7.39 (m, 1H), 7.36 (d, J = 8.4 Hz, 2H), 7.09 (dd, J = 8.0, 2.0 Hz, 1H), 6.65 (br s, 2H), 6.35 (dd, J = 8.0, 4.8 Hz, 1H), 4.45 (br s, 1H), 3.58 (s, 2H), 3.55 - 3.46 (m, 1H), 2.92-2.77 (m, 2H), 2.16 (br t, J = 10 Hz, 2H), 1.95 (br d, J = 11.2 Hz, 2H), 1.63-1.56 (m, 2H), 1.45 (s, 9H). [00339] Step 4: 3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-6-phenyl-3H-i midazo[4,5- b]pyridin-2-yl)pyridin-2-amine WSGR Docket No.62619-716.601 [00340] A mixture of tert-butyl (1-(4-(2-(2-aminopyridin-3-yl)-6-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)carbamate (2.4 g, 4.17 mmol) in HCl/1,4-dioxane (4M, 20 mL) and MeOH (4 mL) was stirred at 25 °C for 2 hr. The reaction mixture was filtered to give a residue (2 g HCl salt, yield: 94.3%). The crude (100 mg) was purified by prep-HPLC (column: Welch Ultimate C18150 x 25mm x 5µm; mobile phase: [water (FA)-ACN]; B%: 0% to 25%, 10min) to give 3-(3-(4-((4-aminopiperidin-1-yl)methyl)phenyl)-6-phenyl-3H-i midazo[4,5- b]pyridin-2-yl)pyridin-2-amine (Intermediate 68, 26.6 mg, 2HCOOH salt, yield: 94%) as a yellow solid. MS: m/z = 476.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ J = 2.0 Hz, 1H), 8.47 (d, J = 2.0 Hz, 1H), 8.34 (s, 2H), 8.00 (dd, J = 4.8, 1.6 Hz, 1H), 7.78 (d, J = 7.6 Hz, 2H), 7.53 (dd, J = 7.6, 7.6 Hz, 2H), 7.47 - 7.39 (m, 5H), 7.20 (dd, J = 7.6, 1.6 Hz, 1H), 7.04 (br s, 2H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 3.55 (s, 2H), 2.98-2.88 (m, 1H), 2.87-2.80 (m, 2H), 2.09-1.97 (m, 2H), 1.90 - 1.80 (m, 2H), 1.57 - 1.44 (m, 2H). [00341] Intermediate 69: 3-(3-(4-((4-(Methylamino)piperidin-1-yl)methyl)phenyl)-5-phe nyl-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00342] Intermediate 69 was prepared in a manner similar to Intermediate 5. MS: m/z = 490.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ J = 8.4 Hz, 1H), 8.07 - 7.94 (m, 4H), 7.53 - 7.43 (m, 6H), 7.41 -7.39 (m, 1H), 7.16 (dd, J = 7.8, 1.2 Hz, 1H), 7.02 (br s, 2H), 6.37 (dd, J = 7.4, 4.8 Hz, 1H), 3.55 (s, 2H), 3.47-3.37 (m, 1H), 2.80 (br d, J = 12.0 Hz, 2H), 2.31 (s, 3H), 2.01 (dd, J = 11.4, 9.8 Hz, 2H), 1.85 - 1.77 (m, 2H), 1.36 - 1.22 (m, 2H). [00343] Intermediate 70: 3-(3-(4-((4-((Methyl-d3)amino)piperidin-1-yl)methyl)phenyl)- 5- phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine WSGR Docket No.62619-716.601 [00344] Step 1: Benzyl 4-((tert-butoxycarbonyl)amino)piperidine-1-carboxylate [00345] To a solution of tert-butyl N-(4-piperidyl)carbamate (12 g, 59.9 mmol) in CH2Cl2 (100 mL) was added TEA (18.2 g, 179 mmol), and then the CbzCl (11.2 g, 65.9 mmol) was added into the mixture at 0 °C. The mixture was stirred at 25 °C for 2 hr. The mixture was concentrated under reduced pressure. The crude was purified by silica gel flash chromatography (Eluent of 10~50% EtOAc in petroleum ether) to give benzyl 4-((tert- butoxycarbonyl)amino)piperidine-1-carboxylate (16 g, yield: 71%) as an off-white solid. ¹ H NMR (400 MHz, Dimethylsulfoxide-d6) J = 13.6 Hz, 2H), 3.50 - 3.34 (m, 2H), 2.89 (s, 2H), 1.71 (d, J = 10.8 Hz, 2H), 1.37 (s, 9H), 1.30 - 1.18 (m, 2H). [00346] Step 2: Benzyl 4-((tert-butoxycarbonyl)(methyl-d3)amino)piperidine-1-carbox ylate [00347] To a solution of benzyl 4-(tert-butoxycarbonylamino)piperidine-1-carboxylate (13 g, 38.9 mmol) in THF (200 mL) was added NaH (4.66 g, 117 mmol) at 0 °C. After stirring at 0 °C for 30 min, CD3I (16.5 g, 117 mmol) was added to the mixture. The mixture was stirred at 25 °C for 16 hr. The mixture was quenched with NH ₄ Cl (aq) (100 mL) at 0 °C. The mixture was duilted with H2O (100 mL) and extrated with CH2Cl2 (200 mL x 2). The combined organic layers were washed with brine (200 mL x 2), dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 0~20% EtOAc in petroleum ether) to give benzyl 4-((tert-butoxycarbonyl)(methyl- d3)amino)piperidine-1-carboxylate (8.6 g, yield: 56%) as a colorless oil. MS: m/z = 252.3 [M + H - 100] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ 7.42 - 7.28 (m, 5H), 5.07 (s, 2H), 4.14 - 3.89 (m, 3H), 2.82 (s, 2H), 1.58 – 1.48 (m, 4H), 1.39 (s, 9H). [00348] Step 3: tert-Butyl (methyl-d3)(piperidin-4-yl)carbamate [00349] To a solution of benzyl 4-[tert-butoxycarbonyl(trideuteriomethyl)amino]piperidine-1- carboxylate (8.6 g, 24.5 mmol) in MeOH (90 mL) was added Pd/C (900 mg, 24.5 mmol). The WSGR Docket No.62619-716.601 mixture was stirred at 25 °C for 16 hr under H2 (15 psi). The mixture was filtered, and the filter cake was washed with MeOH (30 mL). The filtrate was concentrated under reduced pressure to give a tert-butyl (methyl-d ₃ )(piperidin-4-yl)carbamate (5 g, yield: 80%) as a colorless oil. MS: m/z = 218.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 3.93 - 3.62 (m, 1H), 3.26 - 3.16 (m, 1H), 2.95 (d, J = 12.0 Hz, 2H), 2.47 - 2.38 (m, 2H), 1.54 - 1.42 (m, 4H), 1.39 (s, 9H). [00350] Step 4: tert-Butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyr idin-3- yl)benzyl)piperidin-4-yl)(methyl-d3)carbamate [00351] To a solution of Intermediate 4 (1 g, 2.43 mmol) in DMF (10 mL) were added tert- butyl (methyl-d3)(piperidin-4-yl)carbamate (527 mg, 2.43 mmol), NaI (182 mg, 1.21 mmol) and K2CO3 (1.0 g, 7.28 mmol). The mixture was stirred at 80 °C for 18 hr. The reaction mixture was diluted with H ₂ O (20 mL) and extracted with CH ₂ Cl ₂ (20 mL x 3). The combined organic layers were washed with brine (20 mL x 2), dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 0~6% MeOH in CH ₂ Cl ₂ ) to give tert-butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)(methyl-d3)carbamate (750 mg, yield: 49%) as a yellow solid. MS: m/z = 593.3 [M + H] ⁺ . [00352] Step 5: 3-(3-(4-((4-((Methyl-d ₃ )amino)piperidin-1-yl)methyl)phenyl)-5-phenyl-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00353] To a solution of tert-butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)(methyl-d3)carbamate (430 mg, 725 µmol) in CH ₂ Cl ₂ (5 mL) was added TFA (165 mg, 1.45 mmol). The mixture was stirred at 25 °C for 1 hr. The mixture was diluted with H2O (10 mL). The pH of the mixture was adjusted to about 8 with NaHCO ₃ (aq.). The mixture was extracted with CH ₂ Cl ₂ (10 mL x 2). The combined organic layers were washed with brine (10 mL x 2), dried over Na2SO4, filtered, and concentrated under reduced pressure. After purification by prep-TLC (CH2Cl2: MeOH = 5 : 1), 3-(3-(4-((4- ((methyl-d ₃ )amino)piperidin-1-yl)methyl)phenyl)-5-phenyl-3H-imida zo[4,5-b]pyridin-2- yl)pyridin-2-amine (Intermediate 70, 350 mg crude, yield: 50%) was obtained as a light-yellow solid. MS: m/z = 493.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4 8.19 (d, J = 8.4 Hz, 1H), 8.03 (d, J = 7.2 Hz, 2H), 7.98 (dd, J = 4.8, 1.6 Hz, 1H), 7.93 (d, J = 8.4 Hz, 1H), 7.53 (d, J = 8.4 Hz, 2H), 7.47 - 7.35 (m, 5H), 7.32 (dd, J = 7.6, 1.6 Hz, 1H), 6.47 (dd, J = 7.6, 4.8 Hz, 1H), 3.65 (s, 2H), 3.08 - 3.03 (m, 2H), 3.02 - 2.95 (m, 1H), 2.21 - 2.15 (m, 2H), 2.08 - 2.05 (m, 2H), 1.67 - 1.61 (m, 2H). WSGR Docket No.62619-716.601 [00354] Intermediate 71: 3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-2-(2-aminopyr idin-3- yl)-3H-imidazo[4,5-b]pyridin-5-yl)benzonitrile [00355] Step 1: tert-Butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-(3-cyanophenyl)-3H-imidazo[ 4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)carbamate [00356] A mixture of Intermediate 58 (350 mg, 655 µmol), (3-cyanophenyl)boronic acid (116 mg, 786 µmol), K2CO3 (181 mg, 1.31 mmol), and Pd(dppf)Cl2 (24 mg, 33 µmol) in 1,4-dioxane (10 mL) and H ₂ O (2 mL) was degassed and purged with N ₂ three times, and then the mixture was stirred at 100 °C for 16 hr under N2 atmosphere. The reaction mixture was poured into H2O (3 mL), extracted with EtOAc (15 mL). The combined organic layers were dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 0 ~ 9% MeOH in CH2Cl2) to give tert-butyl (1-(4- (2-(2-aminopyridin-3-yl)-5-(3-cyanophenyl)-3H-imidazo[4,5-b] pyridin-3-yl)benzyl)piperidin-4- yl)carbamate (150 mg, yield: 38%) as a yellow solid. MS: m/z = 601.4 [M + H] ⁺ . [00357] Step 2: 3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-2-(2-aminopyr idin-3-yl)-3H- imidazo[4,5-b]pyridin-5-yl)benzonitrile [00358] To a solution of tert-butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-(3-cyanophenyl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)carbamate (50 mg, 73 µmol) in 1,4-dioxane (2 mL) was added 4M HCl in 1,4-dioxane (2 mL). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was filtered to give the filter cake. 3-(3-(4-((4-Aminopiperidin-1- yl)methyl)phenyl)-2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]p yridin-5-yl)benzonitrile (Intermediate 71, 32 mg HCl salt, yield: 87%) was obtained as a yellow solid. MS: m/z = 501.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ J = 8.8 Hz, 1H), 8.06 (d, J = 5.6 Hz, 1H), 7.99 - 7.87 (m, 3H), 7.83 - 7.73 (m, 3H), 7.71 - 7.64 (m, 1H), 6.93 - 6.89 (m, 1H), 3.79 - 3.68 (m, 2H), 3.67 - 3.45 (m, 3H), 3.37 (s, 2H), 2.35 - 2.33 (m, 2H), 2.23 - 2.05 (m, 2H). [00359] Intermediate 72: 3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-5-(cyclohex-1 -en-1- yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine WSGR Docket No.62619-716.601 [00360] Intermediate 72 was prepared in a manner similar to Intermediate 60. MS: m/z = 480.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 J = 8.4 Hz, 1H), 7.98 (dd, J =4.8, 1.2 Hz, 1H), 7.53 (d, J = 8.0 Hz, 1H), 7.45 - 7.40 (m, 2H), 7.38 - 7.32 (m, 2H), 7.14 - 7.07 (m, 1H), 7.01 (br s, 2H), 6.67 - 6.60 (m, 1H), 6.34 (dd, J = 7.6, 4.8Hz, 1H), 3.52 (br s, 2H), 3.49 - 3.48 (m, 1H), 2.76 - 2.73 (m, 2H), 2.44 - 2.43 (m, 2H), 2.20 -2.19 (m, 2H), 2.02 - 1.96 (m, 2H), 1.72 - 1.65 (m, 4H), 1.61 - 1.54 (m, 2H), 1.27 - 1.23 (m, 2H). [00361] Intermediate 73: 3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-5-cyclohexyl- 3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00362] Step 1: tert-Butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-cyclohexyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)carbamate [00363] To a solution of tert-butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-(cyclohex-1-en-1-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)carbamate (refer to Intermediate 72 for detail procedures, 242 mg, 417 µmol) in MeOH (10 mL) was added Pd/C (50 mg, 834 µmol, 10% w/w). The suspension was degassed under reduced pressure and purged with H ₂ several times. The mixture was stirred under H2 (50 psi) at 50 °C for 24 hr under H2. The reaction mixture was cooled to 25 °C, then filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 0 ~ 82% EtOAc in petroleum ether) to give tert-butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-cyclohexyl-3H-imidazo[4,5-b ]pyridin-3- yl)benzyl)piperidin-4-yl)carbamate (182 mg, yield: 75%) as a yellow solid. MS: m/z = 582.3 [M + H] ⁺ . [00364] Step 2: 3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-5-cyclohexyl- 3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine WSGR Docket No.62619-716.601 [00365] To a solution of tert-butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-cyclohexyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)carbamate (182 mg, 345 µmol) in 1,4-dioxane (2 mL) was added 4 M HCl in 1,4-dioxane (2.0 mL). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was filtered to give 3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-5- cyclohexyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (Intermediate 73, 162 mg HCl salt , yield: 91%) was obtained as a yellow solid. MS: m/z = 482.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4 J = 8.0 Hz, 2H), 7.50 - 7.35 (m, 1H), 6.95 - 6.73 (m, 1H), 3.70 (d, J = 12.0 Hz, 2H), 3.64 - 3.40 (m, 2H), 3.33 - 3.31 (m, 3H), 2.88 - 2.70 (m, 1H), 2.30 (d, J = 12.8 Hz, 2H), 2.21 - 2.02 (m, 2H), 1.95 - 1.81 (m, 4H), 1.79 - 1.71 (m, 1H), 1.63 - 1.49 (m, 2H), 1.39 (m, 2H), 1.35 - 1.24 (m, 1H). [00366] Intermediate 74: N-methyl-N-(piperidin-4-yl)acrylamide [00367] Step 1: tert-Butyl 4-(N-methylacrylamido)piperidine-1-carboxylate [00368] To a mixture of tert-butyl 4-(methylamino)piperidine-1-carboxylate (5 g, 23.3 mmol) and DIEA (9.05 g, 69.9 mmol) in THF (200 mL) was added acryloyl chloride (2.11 g, 23.3 mmol) dropwise at 0 °C. The mixture was stirred at 0 °C for 1 hr. The reaction mixture was quenched with MeOH (50 mL) at 0 °C, and then concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (EtOAc in petroleum ether = 0% to 40%) to give tert-butyl 4-(N-methylacrylamido)piperidine-1-carboxylate (6 g, 94% yield) as a white solid. MS: m/z = 213.1 [M - 55] ⁺ . ¹ H NMR (400 MHz, Chloroform-d J = 16.8, 10.4 Hz, 1H), 6.30 (d, J = 16.8 Hz, 1H), 5.69 (d, J = 10.4 Hz, 1H), 4.75 - 4.6 (m, 1H), 4.35 - 4.25 (m, 2H), 2.90 (s, 3H), 2.85 - 2.65 (m, 2H), 1.66 - 1.56 (m, 4H), 1.46 (s, 9H). [00369] Step 2: (N-methyl-N-(piperidin-4-yl)acrylamide [00370] To a solution of tert-butyl 4-(N-methylacrylamido)piperidine-1-carboxylate (150 mg, 2Cl2 (3 mL) was added TFA (1.54 g, 13.5 mmol). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was concentrated under reduced pressure. The crude product N-methyl-N-(piperidin-4-yl)acrylamide (Intermediate 74, 157 mg, TFA salt) was used into the next step without further purification. MS: m/z = 169.1 [M + H] ⁺ . [00371] Intermediate 75: 3-(3-(4-(Chloromethyl)phenyl)-3H-imidazo[4,5-b]pyridin-2- yl)pyridin-2-amine WSGR Docket No.62619-716.601 [00372] Step 1: (4-((3-Nitropyridin-2-yl)amino)phenyl)methanol [00373] To a solution of (4-aminophenyl)methanol (10 g, 81.2 mmol) in 1,4-dioxane (150 mL) were added DIEA (31.5 g, 244 mmol) and 2-chloro-3-nitro-pyridine (15.5 g, 97.4 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was concentrated under reduced pressure. The residue was diluted with H2O (200 mL) and extracted with EtOAc (200 mL × 2). The combined organic layers were washed with brine (500 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The crude was purified by silica gel flash chromatography (Eluent of 0 ~ 82% EtOAc in petroleum ether) to give (4-((3-nitropyridin-2- yl)amino)phenyl)methanol (15.3 g, yield: 77%) as a yellow solid. MS: m/z = 245.8 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d J = 8.4, 2.0 Hz, 1H), 8.48 (dd, J = 4.4, 1.6 Hz, 1H), 7.64 (d, J = 8.0 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H), 6.84 (dd, J = 8.4, 4.8 Hz, 1H), 4.70 (s, 2H). [00374] Step 2: (4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)ph enyl)methanol [00375] To a solution of 4-((3-nitropyridin-2-yl)amino)phenyl)methanol (10 g, 40.8mmol) in DMSO (500 mL) were added Na ₂ S ₂ O ₄ (21.3 g, 122 mmol) and 2-aminopyridine-3-carbaldehyde (5.98 g, 48.9 mmol). The mixture was stirred at 100 °C for 16 hr. The reaction mixture was quenched with H2O (500 mL) at 20 °C and extracted with EtOAc (500 mL × 2). The combined organic layers were washed with brine (500 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. The crude product was purified by silica gel flash chromatography (Eluent of 0 ~ 100% EtOAc in petroleum ether) to give (4-(2-(2-aminopyridin-3-yl)-3H- imidazo[4,5-b]pyridin-3-yl)phenyl)methanol (3.1 g, yield: 24%) as a yellow solid. MS: m/z = 318.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d J = 8.0, 1.2 Hz, 1H), 8.02 (dd, J = 4.8, 1.6 Hz, 1H), 7.52 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), 7.30 - 7.27 (m, 1H), 7.12 (dd, J = 7.6, 1.6 Hz, 1H), 6.65 (br s, 2H), 6.35 (dd, J = 7.6, 4.8 Hz, 1H), 4.76 (s, 2H). WSGR Docket No.62619-716.601 [00376] Step 3: 3-(3-(4-(Chloromethyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl) pyridin-2-amine [00377] To a solution of (4-(2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)phenyl)methanol (1.0 g, 3.15 mmol) in CH ₂ Cl ₂ (10 mL) was added SOCl ₂ (3.3 g, 27.6 mmol). The mixture was stirred at 40 °C for 1 hr. The reaction mixture was concentrated under reduced pressure to give 3-(3-(4-(chloromethyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl) pyridin-2-amine (Intermediate 75, 1.2 g HCl salt) as a gray solid, which was used in the next step without further purification. MS: m/z = 336.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d 8.55 (d, J = 8.0 Hz, 1H), 8.28 (d, J = 7.6 Hz, 1H), 7.91 - 7.83 (m, 1H), 7.68 (d, J = 8.0 Hz, 2H), 7.64 – 7.59 (m, 1H), 7.54 - 7.50 (m, 1H), 7.46 (d, J = 8.0 Hz, 2H), 7.30 – 7.27 (m, 2H), 6.70 – 6.60 (m, 1H), 4.70 (s, 2H). [00378] Intermediate 76: 4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyri din-3- yl)benzyl)piperazin-1-amine hydrochloride [00379] Step 1: tert-Butyl (4-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyr idin-3- yl)benzyl)piperazin-1-yl)carbamate [00380] To a solution of Intermediate 4 (1.50 g, 3.64 mmol) in DMF (5 mL) were added K2CO3 tert-butyl piperazin-1-ylcarbamate (806 mg, 4.01 mmol) at 25 °C. This mixture was stirred at 60 °C for 5 hr. H2O (35 mL) was added to the mixture. The aqueous phase was extracted with EtOAc (30 mL x 3). The combined organic layers were washed with brine (30 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. The crude was purified by silica gel flash chromatography (Eluent of 0 - 10% MeOH in CH2Cl2) to give tert-butyl(4-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo [4,5-b]pyridin-3- yl)benzyl)piperazin-1-yl)carbamate (1.65 g, yield: 79%) as yellow oil. MS: m/z = 577.3 [M + H] ⁺ . [00381] Step 2: 4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyri din-3- yl)benzyl)piperazin-1-amine hydrochloride [00382] To a solution of tert-butyl(4-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo [4,5- b]pyridin-3-yl)benzyl)piperazin-1-yl)carbamate (800 mg, 1.39 mmol) in 1,4-dioxane (10 mL) WSGR Docket No.62619-716.601 The mixture was filtered and concentrated to give 4-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-1-amine hydrochloride (Intermediate 76, 700 mg, HCl salt, yield: 98%) as a yellow solid, which was used in the next step without purification. MS: m/z = 477.3 [M + H]+. [00383] Intermediate 77: 3-(3-(4-(((3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)- yl)methyl)phenyl)-5-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyr idin-2-amine [00384] Intermediate 77 was prepared in a manner similar to Intermediate 76. MS: m/z = 488.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) 8.27 (d, J = 8.0 Hz, 1H), 8.04 - 7.97 (m, 4H), 7.49 - 7.44 (m, 5H), 7.43 - 7.37 (m, 2H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.04 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.60 (s, 2H), 2.85 - 2.76 (m, 2H), 2.58 - 2.51 (m, 7H), 2.31 - 2.26 (m, 2H). [00385] Intermediate 78: 4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyri din-3- yl)benzyl)-N-methylpiperazin-1-amine [00386] Step 1: Benzyl 4-((tert-butoxycarbonyl)amino)piperazine-1-carboxylate [00387] To a solution of tert-butyl N-piperazin-1-ylcarbamate (1 g, 4.98 mmol) in DMF (5 mL) were added TEA (1.39 mL, 9.96 mmol) and CbzCl (934 mg, 5.5 mmol) at 0 °C. The mixture was stirred at 25 °C for 3 hr. The mixture was quenched with H2O (35 mL) and extracted with EtOAc (30 mL x 3). The combined organic layers were washed with brine (30 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. After purification by silica gel flash WSGR Docket No.62619-716.601 chromatography (EtOAc in petroleum ether = 0% to 60%), benzyl 4-((tert- butoxycarbonyl)amino)piperazine-1-carboxylate (1.2 g, 72% yield) was obtained as an off white solid. MS: m/z = 358.1 [M + 23] ⁺ . [00388] Step 2: Benzyl 4-((tert-butoxycarbonyl)(methyl)amino)piperazine-1-carboxyla te [00389] To a mixture of benzyl 4-((tert-butoxycarbonyl)amino)piperazine-1-carboxylate (1.2 g, 3.58 mmol) in THF (10 mL) was added NaH (429 mg, 60% purity) at 0 °C. After stirring at 0 °C for 30 min, CH3I (1.02 g, 7.16 mmol) was added. The resulting mixture was stirred at 25 °C for 5 hr under N ₂ . The reaction was quenched with water (10 mL) at 0 °C and extracted with CH2Cl2 (20 mL x 3). The combined organic layers were washed with brine (30 mL), dried over anhydrous Na2SO4, filtered and concentrated. After purification by silica gel flash chromatography (EtOAc in petroleum ether = 0% to 20%), benzyl 4-((tert- butoxycarbonyl)(methyl)amino)piperazine-1-carboxylate (1.1 g, yield: 88%) was obtained as a colorless oil. MS: m/z = 372.1 [M + 23] ⁺ . [00390] Step 3: tert-Butyl methyl(piperazin-1-yl)carbamate [00391] To a mixture of benzyl 4-((tert-butoxycarbonyl)(methyl)amino)piperazine-1- carboxylate (1.1 g, 3.15 mmol) in MeOH (5 mL) was added Pd/C (1.1 g, 10% purity). The mixture was stirred at 25 °C for 12 hr under H ₂ (50 psi). The mixture was filtered and concentrated to give tert-butyl methyl(piperazin-1-yl)carbamate (670 mg, yield: 99%) as an off- white solid, which was used into the next step without purification. MS: m/z = 160.0 [M – C ₄ H ₇ ]+. ¹ H NMR (400 MHz, Methanol-d ₄ [00392] Step 4: tert-Butyl (4-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyr idin-3- yl)benzyl)piperazin-1-yl)(methyl)carbamate [00393] To a solution of Intermediate 4 (800 mg, 1.94 mmol) and tert-butyl methyl(piperazin-1- K2CO3 (537 mg, 3.88 mmol). The mixture was stirred at 50 °C for 5 hr. The reaction was concentrated, diluted with water (10 mL), and extracted with EtOAc (20 mL x 2). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated. After purification by silica gel flash chromatography (CH2Cl2 in MeOH = 0% to 2%), tert-butyl (4-(4- (2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyridin-3 -yl)benzyl)piperazin-1- yl)(methyl)carbamate (0.35 g, yield: 30%) was obtained as a light yellow solid. MS: m/z = 591.4 [M + 1] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6) 8.27 (d, J = 8.0 Hz, 1H), 8.05 - 7.96 (m, 4H), 7.48 - 7.44 (m, 6H), 7.43 - 7.37 (m, 1H), 7.15 (dd, J = 8.0, 2.0 Hz, 1H), 7.03 (s, 2H), WSGR Docket No.62619-716.601 6.42 - 6.33 (m, 1H), 5.76 - 5.75 (m, 1H), 3.58 (s, 2H), 3.32 - 3.31 (m, 2H), 2.99 - 2.88 (brs, 3H), 2.85 (s, 3H), 2.47 (br s, 3H), 1.41 (s, 9H). [00394] Step 5: 4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyri din-3- yl)benzyl)-N-methylpiperazin-1-amine [00395] To a solution of tert-butyl (4-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b N ₂ . The mixture was concentrated to give 4-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-N-methylpiperazin-1-amine (Intermediate 78, 288 mg, yield: 93.1%, HCl salt) as a yellow solid, which was used in the next step without further purification. MS: m/z = 491.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) 11.6 (br s, 1H), 11.2(br s, 2H), 8.59 - 8.43 (m, 2H), 8.39 - 8.37 (m, 1H), 8.15 - 8.09 (m, 1H), 8.08 - 8.07 (m, 3H), 7.89 - 7.87 (m, 1H), 7.92 - 7.87 (m, 2H), 7.83 - 7.67 (m, 2H), 7.56 - 7.38 (m, 4H), 6.95 - 6.88 (m, 1H), 3.71 - 3.41 (m, 10H), 2.68 (br s, 3H). [00396] Intermediate 79: 3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-5-methyl-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00397] Intermediate 79 was prepared in a manner similar to Intermediate 60. MS: m/z = 414.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4 J = 8.4 Hz, 1H), 7.99 (d, J = 5.6 Hz, 1H), 7.88 (d, J = 7.6 Hz, 2H), 7.81 (d, J = 7.2 Hz, 1H), 7.63 (d, J = 7.6 Hz, 2H), 7.38 (d, J = 8.4 Hz, 1H), 6.88 - 6.82 (m, 1H), 3.70 -3.64 (m, 2H), 3.59 - 3.54 (m, 1H), 3.29 - 3.17 (m, 2H), 2.61 (s, 3H), 2.32 - 2.29 (m, 2H), 2.20 - 2.06 (m, 2H), 1.33 - 1.27 (m, 2H). [00398] Intermediate 80: 3-(3-(4-((4-(Methylamino)piperidin-1-yl)methyl)phenyl)-5- morpholino-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine WSGR Docket No.62619-716.601 [00399] Step 1: Methyl 4-((6-morpholino-3-nitropyridin-2-yl)amino)benzoate [00400] A mixture of methyl 4-((6-chloro-3-nitropyridin-2-yl)amino)benzoate (refer to Intermediate 13 for detail procedures, 2.5 g, 8.13 mmol), morpholine (849 mg, 9.75 mmol), DIEA (2.10 g, 16.2 mmol) in CH ₃ CN (30 mL) was stirred at 90 °C for 2 hr. The reaction mixture was filtered and the filter cake was dried under reduced pressure to give methyl 4-((6- morpholino-3-nitropyridin-2-yl)amino)benzoate (2.94 g, yield: 92%) as a yellow solid. MS: m/z = 359.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) 10.74 (s, 1H), 8.27 (d, J = 9.6 Hz, 1H), 7.98 - 7.94 (m, 2H), 7.83 - 7.79 (m, 2H), 6.58 (d, J = 9.6 Hz, 1H), 3.84 (s, 3H), 3.75 - 3.65 (m, 8H). [00401] Step 2: Methyl 4-(2-(2-aminopyridin-3-yl)-5-morpholino-3H-imidazo[4,5-b]pyr idin-3- yl)benzoate [00402] A mixture of methyl 4-((6-morpholino-3-nitropyridin-2-yl)amino)benzoate (2.94 g, 8.20 mmol), 2-aminonicotinaldehyde (1.10 g, 9.02 mmol), and Na ₂ S ₂ O ₄ (5.71 g, 32.8 mmol) in DMSO (30 mL) was stirred at 100 °C for 16 hr. The reaction mixture was cooled to room temperature and the pH was adjusted to about 9 with sat. NaHCO3. Then the mixture was diluted with H ₂ O (100 mL) and extracted with CH ₂ Cl ₂ (100 mL x 3). The combined organic layers were washed with brine (100 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. The crude was triturated with EtOAc (100 mL) at 20 °C for 30 min to give methyl 4-(2-(2-aminopyridin-3-yl)-5-morpholino-3H-imidazo[4,5-b]pyr idin-3-yl)benzoate (3.5 g, yield: 83%) as a green solid.. MS: m/z = 431.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide- d6 J = 8.4 Hz, 2H), 8.03 - 7.97 (m, 2H), 7.55 (d, J = 8.8 Hz, 2H), 7.32 - 7.13 (m, 3H), 6.93 (d, J = 8.8 Hz, 1H), 6.51 - 6.44 (m, 1H), 3.88 (s, 3H), 3.70 - 3.65 (m, 4H), 3.44 - 3.38 (m, 4H) WSGR Docket No.62619-716.601 [00403] Step 3: (4-(2-(2-Aminopyridin-3-yl)-5-morpholino-3H-imidazo[4,5-b]py ridin-3- yl)phenyl)methanol [00404] A mixture of methyl 4-(2-(2-aminopyridin-3-yl)-5-morpholino-3H-imidazo[4,5- b]pyridin-3-yl)benzoate (3.5 g, 8.13 mmol) in THF (100 mL) was added LiAlH4 (2.5 M, 3.90 mL) dropwise at 0 °C, then the mixture was stirred at 20 °C for 1 hr. The reaction mixture was quenched with Na2SO4·10H2O (5 g) at 0 °C, filtered and concentrated under reduced pressure to give (4-(2-(2-aminopyridin-3-yl)-5-morpholino-3H-imidazo[4,5-b]py ridin-3-yl)phenyl)methanol (2.4 g, yield: 63%) as a green solid. MS: m/z = 403.1 [M + H] ⁺ . [00405] Step 4: 3-(3-(4-(Chloromethyl)phenyl)-5-morpholino-3H-imidazo[4,5-b] pyridin-2- yl)pyridin-2-amine [00406] To a mixture of (4-(2-(2-aminopyridin-3-yl)-5-morpholino-3H-imidazo[4,5-b]py ridin- 3yl)phenyl)methanol (2.4 g, 5.96 mmol) in CH2Cl2 (16 mL) was added SOCl2 (4.26 g, 35.7 mmol,). The mixture was stirred at 40 °C for 1 hr. The reaction mixture was concentrated under reduced pressure to give 3-(3-(4-(chloromethyl)phenyl)-5-morpholino-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine (2.6 g, yield: 64%) as a green solid. MS: m/z = 421.0 [M + H] ⁺ . [00407] Step 5: tert-Butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-morpholino-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)(methyl)carbamate [00408] To a mixture of 3-(3-(4-(chloromethyl)phenyl)-5-morpholino-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine (600 mg, 1.43 mmol) and tert-butyl methyl(piperidin-4- K2CO3 (985 mg, 7.13 mmol). The mixture was stirred at 80 °C for 1 hr. The reaction mixture was diluted with H2O (30 mL), filtered and concentrated under reduced pressure. After purification by silica gel flash chromatography (EtOAc in petroleum ether = 0% to 60%), tert- butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-morpholino-3H-imidazo[4,5-b ]pyridin-3- yl)benzyl)piperidin-4-yl)(methyl)carbamate (400 mg, yield: 41%) was obtained as a yellow solid. MS: m/z = 599.3 [M + H] ⁺ . [00409] Step 6: 3-(3-(4-((4-(Methylamino)piperidin-1-yl)methyl)phenyl)-5-mor pholino-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00410] To a mixture of tert-butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-morpholino-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)(methyl)car bamate CH2Cl2 (5 mL) was added HCl/1,4-dioxane (4 M, 1 mL). The mixture was stirred at 20 °C for 2 hr. The reaction mixture was concentrated under reduced pressure to give 3-(3-(4-((4- (methylamino)piperidin-1-yl)methyl)phenyl)-5-morpholino-3H-i midazo[4,5-b]pyridin-2- WSGR Docket No.62619-716.601 yl)pyridin-2-amine (Intermediate 80, 260 mg, HCl salt, yield: 41%) as a yellow solid. MS: m/z = 499.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ J = 8.0 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 7.19 (d, J = 7.6, 1.6 Hz, 1H), 6.87 (d, J = 8.8 Hz, 1H), 6.41 (d, J = 7.6, 4.8 Hz, 1H), 3.80 - 3.70 (m, 4H), 3.56 (s, 2H), 3.51 - 3.44 (m, 4H), 2.95 - 2.85 (m, 2H), 2.50 - 2.37 (m, 1H), 2.36 (s, 3H), 2.14 - 2.04 (m, 2H), 1.96 - 1.84 (m, 2H), 1.46 - 1.34 (m, 2H). [00411] Intermediate 81: 3-(3-(4-(Chloromethyl)phenyl)-5-cyclopropyl-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine [00412] Step 1: Methyl 4-((6-cyclopropyl-3-nitropyridin-2-yl)amino)benzoate [00413] To a solution of methyl 4-((6-chloro-3-nitropyridin-2-yl)amino)benzoate (refer to Intermediate 13 for detail procedures, 30 g, 97.5 mmol) in 1,4-dioxane (300 mL) were added cyclopropylboronic acid (12.6 g, 146 mmol), Cs ₂ CO ₃ (95.3 g, 292 mmol) and H ₂ O (50 mL) at 25 °C. The mixture was stirred at 100°C for 12 hr under N ₂ . The reaction mixture was poured into H2O (500 mL) and extracted with CH2Cl2 (200 mL x 2). The combined organic layers were washed with brine (400 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. The residue was purified by silica gel flash chromatography (Eluent of 0~50% EtOAc in petroleum ether, and then use CH2Cl2 directly) to give methyl 4-((6-cyclopropyl-3-nitropyridin-2- yl)amino)benzoate (25 g, yield: 74%) as an off-white solid. MS: m/z = 314.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ J = 8.4 Hz, 1H), 7.94 (d, J = 8.4 Hz, 2H), 7.80 (d, J = 8.8 Hz, 2H), 7.05 (d, J = 8.4 Hz, 1H), 3.84 (s, 3H), 2.28 - 2.18 (m, 1H), 1.15 - 1.08 (m, 2H), 1.07 - 1.01 (m, 2H). [00414] Step 2: Methyl 4-(2-(2-aminopyridin-3-yl)-5-cyclopropyl-3H-imidazo[4,5-b]py ridin-3- yl)benzoate WSGR Docket No.62619-716.601 [00415] To a solution of methyl 4-((6-cyclopropyl-3-nitropyridin-2-yl)amino)benzoate (20 g, 63.8 mmol) in DMSO (500 mL) were added 2-aminopyridine-3-carbaldehyde (9.4 g, 76.6 mmol) and Na ₂ S ₂ O ₄ (44.5 g, 255 mmol) at 25 °C. The mixture was stirred at 100 °C for 12 hr. The reaction mixture was poured into H2O (500 mL) and then extracted with CH2Cl2 (200 mL x 2). The combined organic layers were washed with brine (400 mL), dried over anhydrous Na2SO4, filtered and concentrated to dryness. The residue was purified by silica gel flash chromatography (Eluent of 1~3% MeOH in CH2Cl2) to give methyl 4-(2-(2-aminopyridin-3-yl)- 5-cyclopropyl-3H-imidazo[4,5-b]pyridin-3-yl)benzoate (10 g, yield: 37%) as a red solid. MS: m/z = 386.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 (dd, J = 5.6, 1.6 Hz, 1H), 7.57 (d, J = 8.4 Hz, 2H), 7.41 - 7.27 (m, 4H), 6.59 (dd, J = 7.6, 5.2 Hz, 1H), 3.89 (s, 3H), 2.24 - 2.17 (m, 1H), 0.98 - 0.92 (m, 2H), 0.87 - 0.82 (m, 2H). [00416] Step 3: (4-(2-(2-Aminopyridin-3-yl)-5-cyclopropyl-3H-imidazo[4,5-b]p yridin-3- yl)phenyl)methanol [00417] To a solution of methyl 4-(2-(2-aminopyridin-3-yl)-5-cyclopropyl-3H-imidazo[4,5- b]pyridin-3-yl)benzoate (2 g, 5.2 mmol) in THF (50 mL) was added LiAlH4 (3.1 mL, 2.5M) at 0 °C. The mixture was stirred at 0 °C for 1.5 hr, and then was quenched with Na ₂ SO ₄ ·10H ₂ O (8 g) at 0 °C. The mixture was filtered, and the filter cake was washed by CH ₂ Cl ₂ (30 mL x 2). The filtrate was concentrated under reduced pressure to give (4-(2-(2-aminopyridin-3-yl)-5- cyclopropyl-3H-imidazo[4,5-b]pyridin-3-yl)phenyl)methanol (1.8 g, crude) as a yellow solid, which was used in the next step without further purification. MS: m/z = 358.0 [M ] ⁺ . [00418] Step 4: 3-(3-(4-(Chloromethyl)phenyl)-5-cyclopropyl-3H-imidazo[4,5-b ]pyridin-2- yl)pyridin-2-amine [00419] To a solution of (4-(2-(2-aminopyridin-3-yl)-5-cyclopropyl-3H-imidazo[4,5-b]p yridin- 3-yl)phenyl)methanol (1.4 g, 3.9 mmol) in CH2Cl2 (20 mL) was added SOCl2 (2.8 g, 23.5 mmol) dropwise at 25 °C. The mixture was stirred at 40 °C for 1 hr. The reaction mixture was concentrated to give 3-(3-(4-(chloromethyl)phenyl)-5-cyclopropyl-3H-imidazo[4,5-b ]pyridin-2- yl)pyridin-2-amine (Intermediate 81, 1.43 g, yield: 93%) as an off-white solid. MS: m/z = 376.0 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 2H), 7.81 (dd, J = 7.2, 1.6 Hz, 1H), 7.60 (d, J = 8.0 Hz, 2H), 7.48 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 8.4 Hz, 1H), 6.87 (dd, J = 7.6, 6.0 Hz, 1H), 4.85 (s, 2H), 2.27 - 2.17 (m, 1H), 1.00 - 0.92 (m, 2H), 0.88 - 0.81 (m, 2H). [00420] Intermediate 82: 3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-5-morpholino- 3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine WSGR Docket No.62619-716.601 [00421] Step 1: tert-Butyl (1-(4-((6-morpholino-3-nitropyridin-2-yl)amino)benzyl)piperi din-4- yl)carbamate [00422] A mixture of tert-butyl (1-(4-((6-chloro-3-nitropyridin-2-yl)amino)benzyl)piperidin- 4- yl)carbamate (refer to Intermediate 3 for detail procedures, 3 g, 6.49 mmol), morpholine (678 mg, 7.79 mmol), and DIEA (1.68 g, 12.9 mmol) in MeCN (40 mL) was stirred at 90 °C for 2 hr. The reaction mixture was diluted with H ₂ O (100 mL) and extracted with CH ₂ Cl ₂ (100 mL x 3). The combined organic layers were washed with H ₂ O (50 mL x 2), dried over Na ₂ SO ₄ , filtered and concentrated to give tert-butyl (1-(4-((6-morpholino-3-nitropyridin-2- yl)amino)benzyl)piperidin-4-yl)carbamate (3.24 g, yield: 97%) as a yellow solid, which was used in the next step without further purification. MS: m/z = 513.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) 10.70 (s, 1H), 8.32 (d, J = 9.2 Hz, 1H), 7.52 (d, J = 8.4 Hz, 2H), 7.30 (d, J = 8.0 Hz, 2H), 6.12 (d, J = 9.6 Hz, 1H), 4.53 - 4.34 (m, 1H), 3.79 - 3.75 (m, 4H), 3.75 - 3.55 (m, 4H), 3.48 (s, 3H), 2.90 - 2.75 (m, 2H), 2.15 - 2.05 (m, 2H), 1.95 - 1.75 (m, 2H), 1.76 - 1.53 (m, 2H), 1.44 (s, 9H). [00423] Step 2: 3-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-5-morpholino- 3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine [00424] A mixture of tert-butyl (1-(4-((6-morpholino-3-nitropyridin-2- yl)amino)benzyl)piperidin-4-yl)carbamate (3.24 g, 6.32 mmol), 2-aminopyridine-3- carbaldehyde (926 mg, 7.58 mmol), Na ₂ S ₂ O ₄ (3.88 g, 18.9 mmol) in DMSO (90 mL) was stirred at 100 °C for 24 hr. The reaction mixture was diluted with H2O (200 mL) and extracted with CH ₂ Cl ₂ (50 mL x 3). The pH of the mixture was adjusted to about 8~9 using sat. Na ₂ CO ₃ (100 mL). The mixture was extracted with EtOAc (50 mL x 6), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (Eluent of 0 ~ 7% MeOH in CH ₂ Cl ₂ ) to give 3-(3-(4-((4-aminopiperidin-1- yl)methyl)phenyl)-5-morpholino-3H-imidazo[4,5-b]pyridin-2-yl )pyridin-2-amine (Intermediate 82, 1.2 g, yield: 29%) as a yellow solid. MS: m/z = 485.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide- d ₆ 7.98 (d, J = 8.8 Hz, 1H), 7.96 (dd, J = 4.8, 2.0 Hz, 1H), 7.40 (d, J = 8.4 Hz, 2H), 7.29 (d, J = 8.4 Hz, 2H), 7.03 (br s, 2H), 6.98 (dd, J = 8.0, 1.6 Hz, 1H), 6.89 (d, J = 8.8 WSGR Docket No.62619-716.601 Hz, 1H), 6.30 (dd, J = 8.0, 4.8 Hz, 1H), 3.69 - 3.65 (m, 4H), 3.50 (s, 2H), 3.41 - 3.38 (m, 5H), 2.78 - 2.70 (m, 2H), 2.02 - 1.92 (m, 2H), 1.70 - 1.64 (m, 2H), 1.35 - 1.16 (m, 2H). [00425] Intermediate 83: 3-(3-(4-((4-(Cyclopropylamino)piperidin-1-yl)methyl)phenyl)- 5- phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00426] Step 1: Benzyl 4-(cyclopropylamino)piperidine-1-carboxylate [00427] To a solution of benzyl 4-oxopiperidine-1-carboxylate (500 mg, 2.14 mmol) in CH2Cl2 (5 mL) were added cyclopropanamine (184 mg, 3.22 mmol, HCl salt) and AcOH (193 mg, 3.22 mmol). The mixture was stirred at 25 °C for 1 hr, and then NaBH(OAc)3 (681 mg, 3.22 mmol) was added. The resulting mixture was stirred at 25 °C for 16 hr. The reaction mixture was quenched with H ₂ O (10 mL) at 25 °C, diluted with CH ₂ Cl ₂ (10 mL), and extracted with CH ₂ Cl ₂ (15 mL x 2). The combined organic layers were washed with brine (15 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. Benzyl 4-(cyclopropylamino)piperidine-1- carboxylate (580 mg, yield: 93%) was obtained as a yellow oil. MS: m/z = 275.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d 2.85 (m, 2H), 2.82 - 2.71 (m, 1H), 2.17 - 2.09 (m, 1H), 1.97 - 1.88 (m, 2H), 1.76 - 1.65 (m, 2H), 1.32 - 1.23 (m, 2H), 0.48 - 0.42 (m, 2H), 0.36 - 0.30 (m, 2H). [00428] Step 2: Benzyl 4-((tert-butoxycarbonyl)(cyclopropyl)amino)piperidine-1-carb oxylate [00429] To a solution of benzyl 4-(cyclopropylamino)piperidine-1-carboxylate (580 mg, 2.11 mmol) in THF (10 mL) and H ₂ O (5 mL) were added Na ₂ CO ₃ (672 mg, 6.34 mmol) and (Boc) ₂ O (554 mg, 2.54 mmol). The mixture was stirred at 25 °C for 16 hr. The reaction mixture was quenched with H2O (5 mL) at 25 °C, diluted with CH2Cl2 (10 mL) and extracted with CH2Cl2 (15 mL x 2). The combined organic layers were washed with brine (15 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. Benzyl 4-((tert- butoxycarbonyl)(cyclopropyl)amino)piperidine-1-carboxylate (800 mg, yield: 91%) was WSGR Docket No.62619-716.601 obtained as a yellow oil. MS: m/z = 397.2 [M + Na] ⁺ . ¹ H NMR (400 MHz, Chloroform-d 7.45 - 7.27 (m, 5H), 5.12 (s, 2H), 4.35 - 4.17 (m, 2H), 3.84 - 3.72 (m, 1H), 2.86 - 2.71 (m, 2H), 2.36 - 2.25 (m, 1H), 1.97 - 1.82 (m, 2H), 1.76 - 1.66 (m, 2H), 1.52 (s, 9H), 0.79 - 0.71 (m, 2H), 0.68 - 0.59 (m, 2H). [00430] Step 3: tert-Butyl cyclopropyl(piperidin-4-yl)carbamate [00431] To a solution of benzyl 4-((tert-butoxycarbonyl)(cyclopropyl)amino)piperidine-1- carboxylate (500 mg, 1.34 mmol) in MeOH (10 mL) was added Pd/C (150 mg, 10% purity) under N ₂ atmosphere. The mixture was purged with H ₂ three times and stirred at 40 °C under H ₂ atmosphere (40 Psi) for 16 hr. The mixture was filtered and washed with MeOH (10 mL x 2). The filtrate was concentrated to give tert-butyl cyclopropyl(piperidin-4-yl)carbamate (280 mg, yield: 83%) as a white oil. ¹ H NMR (400 MHz, Chloroform-d 3.77 - 3.68 (m, 1H), 3.13 - 3.07 (m, 2H), 2.67 - 2.57 (m, 2H), 2.36 - 2.28 (m, 1H), 1.93 - 1.82 (m, 2H), 1.74 - 1.67 (m, 2H), 1.63 - 1.55 (m, 1H), 1.45 (s, 9H), 0.76 - 0.71 (m, 2H), 0.68 - 0.62 (m, 2H). [00432] Step 4: tert-Butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyr idin-3- yl)benzyl)piperidin-4-yl)(cyclopropyl)carbamate [00433] ₂ CO ₃ tert-butyl cyclopropyl(piperidin-4- yl)carbamate (350 mg, 1.46 mmol). The mixture was stirred at 25 °C for 16 hr. The reaction mixture was quenched with H2O (10 mL) at 25 °C, diluted with EtOAc (15 mL) and washed with H ₂ O (20 mL x 3). The combined organic layers were washed with brine (20 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. After purification by silica gel flash chromatography ( MeOH in CH2Cl2 = 1% to 5%), tert-butyl (1-(4-(2-(2-aminopyridin-3- yl)-5-phenyl-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin- 4-yl)(cyclopropyl)carbamate (400 mg, yield: 83%) was obtained as a yellow solid. MS: m/z = 616.3 [M + H] ⁺ . [00434] Step 5: 3-(3-(4-((4-(Cyclopropylamino)piperidin-1-yl)methyl)phenyl)- 5-phenyl-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00435] To a solution of tert-butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b CH2Cl2 (3 the mixture was adjusted to 8 with saturated NaHCO3. The mixture was diluted with CH2Cl2 (15 mL), extracted with CH2Cl2 (20 mL x 3). The combined organic layers were washed with brine (20 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure, 3-(3-(4-((4- (Cyclopropylamino)piperidin-1-yl)methyl)phenyl)-5-phenyl-3H- imidazo[4,5-b]pyridin-2- WSGR Docket No.62619-716.601 yl)pyridin-2-amine (Intermediate 83, 130 mg, yield: 96%) was obtained as a yellow solid. MS: m/z = 516.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ J = 8.4 Hz, 1H), 8.05 - 7.97 (m, 4H), 7.49 - 7.42 (m, 6H), 7.41 - 7.38 (m, 1H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.01 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.58 (s, 2H), 2.91 - 2.82 (m, 2H), 2.81 - 2.71 (m, 1H), 2.13 - 2.00 (m, 2H), 1.95 - 1.88 (m, 2H), 1.48 - 1.37 (m, 2H), 1.29 - 1.14 (m, 2H), 0.59 - 0.48 (m, 2H), 0.47 - 0.34 (m, 2H). [00436] Intermediate 84: 3-(3-(4-((4-(Ethylamino)piperidin-1-yl)methyl)phenyl)-5-phen yl-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00437] Step 1: tert-Butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyr idin-3- yl)benzyl)piperidin-4-yl)(ethyl)carbamate [00438] ₂ CO ₃ tert-butyl ethyl(piperidin-4-yl)carbamate The reaction mixture was poured into H ₂ O (20 mL). The aqueous phase was extracted with CH ₂ Cl ₂ (20 mL x 2). The combined organic layers were washed with brine (20 mL x 2), dried over anhydrous Na2SO4, filtered and concentrated. tert-Butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)(ethyl)carbamate (320 mg, yield: 69%) was obtained as a yellow solid. MS: m/z = 604.2 [M + H] ⁺ . [00439] Step 2: 3-(3-(4-((4-(Ethylamino)piperidin-1-yl)methyl)phenyl)-5-phen yl-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00440] To a solution of tert-butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)(ethyl)carbamate (320 mg, 530 µmol) in 1,4-dioxane (3.0 mL) was added 4M HCl in 1,4-dioxane (3.0 mL). The mixture was stirred at 25 °C for 0.5 hr. The mixture was concentrated to give 3-(3-(4-((4-(ethylamino)piperidin-1-yl)methyl)phenyl)-5- phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (Intermediate 84, 230 mg HCl salt) as a yellow solid. MS: m/z = 504.3. [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ J = 8.0 Hz, 1H), 8.06 - 7.96 (m, 4H), 7.49 - 7.38 (m, 7H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 7.03 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 3.54 (s, 2H), 2.82 - 2.73 (m, 2H), 2.58 - 2.52 (m, 2H), 2.40 WSGR Docket No.62619-716.601 - 2.34 (m, 1H), 2.03 - 1.93 (m, 2H), 1.82 - 1.74 (m, 2H), 1.32 - 1.21 (m, 2H), 0.99 (t, J = 7.2 Hz, 3H). [00441] Intermediate 85: 4-(3-(4-((4-Aminopiperidin-1-yl)methyl)phenyl)-2-(2-aminopyr idin-3- yl)-3H-imidazo[4,5-b]pyridin-5-yl)benzonitrile [00442] Intermediate 85 was prepared in a manner similar to Intermediate 71. MS: m/z = 501.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d J = 2.4 Hz, 1H), 8.22 (d, J = 2.4 Hz, 1H), 8.03 (d, J = 8.4 Hz, 1H), 8.00 - 7.97 (m, 1H), 7.82 - 7.71 (m, 2H), 7.56 - 7.34 (m, 5H), 7.34 - 7.29 (m, 1H), 6.46 (dd, J = 7.6, 5.2 Hz, 1H), 3.69 - 3.63 (m, 1H), 3.61 (s, 2H), 2.95 - 2.89 (m, 2H), 2.17 - 2.10 (m, 2H), 1.87 - 1.81 (m, 2H), 1.49 - 1.42 (m, 2H). [00443] Example 1: N-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyri din-3- yl)benzyl)acrylamide [00444] To a solution of Intermediate 1 (200 mg, 510 mmol) and acrylic acid (44 mg, 612 mmol) in DMF (4 mL) was added DIEA (329 mg, 2.55 mmol), HOBt (103 mg, 764 mmol) and EDCI (147 mg, 764 mmol). The mixture was stirred at 25 °C for 12 hr. The reaction mixture was filtered, the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (column: Waters xbridge 150*25 mm 10 mm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; B%: 32% - 62%, 10 min), N-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)acrylamide (Example 1, 9.1 mg, yield: 4%) was obtained as a light-yellow solid. MS: m/z = 447.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 8.72 (t, J = 6.0 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.05 - 7.95 (m, 4H), 7.50 - 7.38 (m, 7H), 7.21 (dd, J = 7.6, 2.0 Hz, 1H), 6.94 (br s, 2H), 6.42 (dd, J = 7.6, 5.2 Hz, 1H), 6.32 (dd, J = 17.2, 10.0 Hz, 1H), 6.16 (dd, J = 17.2, 2.0 Hz, 1H), 5.65 (dd, J = 10.0, 2.0 Hz, 1H), 4.47 (d, J = 6.0 Hz, 1H). WSGR Docket No.62619-716.601 [00445] Example 2: 1-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)piperazin-1-yl)prop-2-en-1-one [00446] To a solution of Intermediate 2 (150 mg, 325 mmol) and prop-2-enoyl chloride (58.8 mg, 650 mmol) in THF (3 mL) was added TEA (164 mg, 1.62 mmol). The mixture was stirred at 0 °C for 1 hr. The reaction mixture was filtered, the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (column: Waters xbridge 150*25 mm 10 mm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; B%: 40% - 70%, 5 min) to give 1-(4-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3-yl)benzyl)piperazin-1- yl)prop-2-en-1-one (Example 2, 25.3 mg, yield: 15%) as a light-yellow solid. MS: m/z = 516.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ J = 8.4 Hz, 1H), 8.06 - 7.95 (m, 4H), 7.52 - 7.43 (m, 6H), 7.42 - 7.36 (m, 1H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 7.02 (br s, 2H), 6.80 (dd, J = 16.8, 10.4 Hz, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 6.11 (dd, J = 16.8, 2.4 Hz, 1H), 5.68 (dd, J = 10.4, 2.4 Hz, 1H), 3.62 (s, 2H), 3.61 - 3.55 (m, 4H), 2.43-2.38 (m, 4H). [00447] Example 3: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)piperidin-4-yl)acrylamide [00448] To a solution of Intermediate 3 (150 mg, 315 mmol) and prop-2-enoyl chloride (57.1 mg, 631 mmol) in THF (3 mL) and DMF (0.5 mL) was added DIEA (204 mg, 1.58 mmol). The mixture was stirred at 0 °C for 4 hr. The reaction mixture was filtered, the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (column: Waters xbridge 150*25mm 10 mm; mobile phase: [water (NH4HCO3) - ACN]; B%: 37% - 67%, 5 min) to give N-(1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)acrylamide (Example 3, 33.4 mg, yield: 20%) as an off- white solid. MS: m/z = 530.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 J = 8.4 Hz, 1H), 8.05 – 7.95 (m, 5H), 7.50 – 7.36 (m, 7H), 7.16 (d, J = 7.6 Hz, 1H), 7.02 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 6.21 (dd, J = 17.2, 10.0 Hz, 1H), 6.06 (dd, J = 17.2, 2.0 Hz, WSGR Docket No.62619-716.601 1H), 5.56 (dd, J = 10.0, 2.0 Hz, 1H), 3.67 – 3.59 (m, 1H), 3.57 (s, 2H), 2.85 - 2.76 (m, 2H), 2.08 (t, J = 10.4 Hz, 2H), 1.80 - 1.74 (m, 2H), 1.50 - 1.40 (m, 2H). [00449] Example 4: N-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyri din-3- yl)benzyl)ethenesulfonamide [00450] To a solution of Intermediate 1 (50 mg, 127 mmol) in THF (1 mL) was added TEA (12.9 mg, 127 mmol) and 2-chloroethanesulfonyl chloride (20.8 mg, 127 mmol) at 0 °C. The mixture was stirred at 0 °C for 1 hr. Then the mixture was filtered and concentrated under reduced pressure. The residue was purified by prep-TLC (CH ₂ Cl ₂ : MeOH = 10 : 1) to give N- (4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyridi n-3-yl)benzyl)ethenesulfonamide (Example 4, 8.7 mg, yield: 14%) as a yellow solid. MS: m/z = 483.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ J = 8.4 Hz, 1H), 8.11 - 7.89 (m, 5H), 7.55 - 7.43 (m, 6H), 7.42 - 7.38 (m, 1H), 7.22 (dd, J = 7.6, 1.6 Hz, 1H), 6.94 (br s, 2H), 6.70 (dd, J = 16.4, 10.0 Hz, 1H), 6.42 (dd, J = 7.6, 4.8 Hz, 1H), 6.05 (d, J = 16.4 Hz, 1H), 5.95 (d, J = 10.0 Hz, 1H), 4.17 (s, 2H). [00451] Example 5: 3-(5-Phenyl-3-(4-((4-(vinylsulfonyl)piperazin-1-yl)methyl)ph enyl)-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00452] To a solution of Intermediate 2 (200 mg, 433 µmol) and ethenesulfonyl chloride (55 mg, 433 µmol) in CH2Cl2 (5 mL) was added TEA (219 mg, 2.17 mmol). The mixture was stirred at 25 °C for 14 hr. The reaction mixture was filtered and concentrated under reduced pressure. The crude was purified by prep-HPLC (column: Agela DuraShell C18150*25 mm 5 µm; mobile phase: [water (NH3H2O) - ACN]; B %: 42 % - 72 %, 10 min), 3-(5-phenyl-3-(4-((4- (vinylsulfonyl)piperazin-1-yl)methyl)phenyl)-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine (Example 5, 4.1 mg, yield: 1.7 %) was obtained as a yellow solid. MS: m/z = 552.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 J = 8.4 Hz, 1H), 8.04 - 7.97 (m, 4H), 7.50 - 7.43 (m, 6H), 7.41 - 7.38 (m, 1H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 7.02 (br s, 2H), 6.83 (dd, J = WSGR Docket No.62619-716.601 16.8, 10.4 Hz, 1H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 6.19 (d, J = 10.4 Hz, 1H), 6.12 (d, J = 16.8 Hz, 1H), 3.63 (s, 2H), 3.10 - 3.06 (m, 4H), 2.62 - 2.55 (m, 4H). [00453] Example 6: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)piperidin-4-yl)ethenesulfonamide [00454] Example 6 was prepared in a manner similar to Example 5. MS: m/z = 566.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 J = 8.4 Hz, 1H), 8.06 - 7.96 (m, 4H), 7.49 - 7.33 (m, 8H), 7.15 (dd, J = 7.6, 2.0 Hz, 1H), 7.01 (br s, 2H), 6.74 (dd, J = 16.4, 10.0 Hz, 1H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 6.03 (d, J = 16.4 Hz, 1H), 5.91 (d, J = 10.0 Hz, 1H), 3.53 (s, 2H), 3.05 - 2.92 (m, 1H), 2.80 - 2.73 (m, 2H), 2.06 - 1.97 (m, 2H), 1.82 - 1.73 (m, 2H), 1.57 - 1.44 (m, 2H). [00455] Example 7: (E)-1-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5 -b]pyridin- 3-yl)benzyl)piperazin-1-yl)-3-methoxyprop-2-en-1-one [00456] To a solution of Intermediate 2 (200 mg, 329 mmol) and TEA (66.6 mg, 659 mmol) in CH ₂ Cl ₂ (4 mL) was added (E)-3-methoxyacrylic acid (43.7 mg, 428 mmol), EDCI (94.7 mg, 494 mmol) and DMAP (4.02 mg, 32.9 mmol). The mixture was stirred at 25 °C for 12 hr. The reaction mixture was diluted with H2O (10 mL) and extracted with CH2Cl2 (10 mL× 3). The combined organic layers were dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. The residue was purified by prep-HPLC (column: [water (NH4HCO3) - ACN]; B%: 32% - 62%, 15 min), (E)-1-(4-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5 -b]pyridin- 3-yl)benzyl)piperazin-1-yl)-3-methoxyprop-2-en-1-one (Example 7, 26.3 mg, yield: 14.1 %) was obtained as a yellow solid. MS: m/z = 546.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) J = 8.4 Hz, 1H), 8.03 (d, J = 7.6 Hz, 2H), 7.98 (dd, J = 4.8, 1.6 Hz, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.58 - 7.51 (m, 3H), 7.48 - 7.40 (m, 4H), 7.39 - 7.35 (m, 1H), 7.34 - 7.29 (m, 1H), 6.48 (dd, J = 7.6, 5.2 Hz, 1H), 5.82 (d, J = 12.0 Hz, 1H), 3.73 (s, 3H), 3.69 - 3.62 (m, 6H), 2.55 - 2.48 (m, 4H). WSGR Docket No.62619-716.601 [00457] Example 8: (E)-N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5 -b]pyridin- 3-yl)benzyl)piperidin-4-yl)-3-methoxyacrylamide [00458] Example 8 was prepared in a manner similar to Example 7. MS: m/z = 560.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4 J = 8.4 Hz, 1H), 8.06 - 8.01 (m, 2H), 7.98 (dd, J = 5.2, 2.0 Hz, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.56 - 7.52 (m, 2H), 7.49 - 7.40 (m, 5H), 7.40 - 7.36 (m, 1H), 7.33 (dd, J = 7.6, 2.0 Hz, 1H), 6.48 (dd, J = 7.6, 5.2 Hz, 1H), 5.36 (d, J = 12.4 Hz, 1H), 3.78 - 3.71 (m, 1H), 3.67 (s, 3H), 3.64 (s, 2H), 2.97 – 2.91 (m, 2H), 2.26 - 2.18 (m, 2H), 1.93 – 1.87 (m, 2H), 1.61 - 1.51 (m, 2H). [00459] Example 9: 1-(6-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)-2,6-diazaspiro[3.3]heptan-2-yl)prop-2-en-1-one [00460] Example 9 was prepared in a manner similar to Example 2. MS: m/z = 528.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 J = 8.4 Hz, 1H), 8.07 - 7.93 (m, 5H), 7.49 - 7.38 (m, 8H), 7.15 (dd, J = 8.0, 2.0 Hz, 1H), 6.99 (br s, 2H), 6.40 (dd, J = 4.8, 7.6 Hz, 1H), 6.26 (dd, J = 17.2, 10.4 Hz, 1H), 6.07 (dd, J = 17.2, 2.4 Hz, 1H), 5.65 (dd, J = 10.4, 2.4 Hz, 1H), 4.30 (s, 2H), 4.02 (d, J = 15.2 Hz, 4H), 3.62 (s, 2H). [00461] Example 10: (S)-N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5 -b]pyridin- 3-yl)benzyl)piperidin-3-yl)acrylamide [00462] Example 10 was prepared in a manner similar to Example 2. MS: m/z = 530.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4 8.19 (d, J = 8.4 Hz, 1H), 8.06 - 8.01 (m, 2H), 7.98 - 7.92 (m, 2H), 7.55 (d, J = 8.4 Hz, 2H), 7.45 - 7.42 (m, 3H), 7.41 - 7.33 (m, 2H), 7.29 (dd, J = WSGR Docket No.62619-716.601 7.6, 1.6 Hz, 1H), 6.47 (dd, J = 7.6, 5.2 Hz, 1H), 6.30 - 6.15 (m, 2H), 5.65 (dd, J = 9.2, 2.8 Hz, 1H), 4.05 - 3.98 (m, 1H), 3.70 - 3.59 (m, 2H), 2.90 - 2.88 (m, 1H), 2.81 - 2.69 (m, 1H), 2.28 - 2.16 (m, 1H), 2.12 - 2.00 (m, 1H), 1.89 - 1.75 (m, 2H), 1.73 - 1.61 (m, 1H), 1.39 - 1.29 (m, 1H). [00463] Example 11: (S)-N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5 -b]pyridin- 3-yl)benzyl)pyrrolidin-3-yl)acrylamide [00464] Example 11 was prepared in a manner similar to Example 2. MS: m/z = 516.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4 8.19 (d, J = 8.4 Hz, 1H), 8.04 – 8.02 (m, 2H), 7.97 (dd, J = 5.2, 1.6 Hz, 1H), 7.94 (d, J = 8.8 Hz, 1H), 7.56 (d, J = 8.4 Hz, 2H), 7.45 (d, J = 8.0 Hz, 2H), 7.43 - 7.34 (m, 3H), 7.31 (dd, J = 7.6, 1.6 Hz, 1H), 6.47 (dd, J = 7.6, 5.2 Hz, 1H), 6.24 - 6.22 (m, 2H), 5.65 (dd, J = 8.0, 4.0 Hz, 1H), 4.49 - 4.40 (m, 1H), 3.80 - 3.72 (m, 2H), 2.93 - 2.79 (m, 2H), 2.64 - 2.50 (m, 2H), 2.38 - 2.27 (m, 1H), 1.79 - 1.69 (m, 1H). [00465] Example 12: N-(2-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)-2-azaspiro[4.5]decan-8-yl)acrylamide [00466] Example 12 was prepared in a manner similar to Example 2. MS: m/z = 584.4 [M + H] ⁺ .1H NMR (400 MHz, Methanol-d4 J = 8.4 Hz, 1H), 8.04 (d, J = 7.6 Hz, 2H), 8.00 - 7.93 (m, 2H), 7.57 – 7.54 (m, 2H), 7.46 (d, J = 8.4 Hz, 2H), 7.43 - 7.32 (m, 4H), 6.49 – 6.46 (m, 1H), 6.22 - 6.17 (m, 2H), 5.64 - 5.59 (m, 1H), 3.76 –3.68 (m, 3H), 2.75 - 2.68 (m, 2H), 2.56 – 2.47 (m, 2H), 1.82 - 1.66 (m, 6H), 1.51 - 1.31 (m, 4H). [00467] Example 13: (R)-N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5 - b]pyridin-3-yl)benzyl)piperidin-3-yl)acrylamide WSGR Docket No.62619-716.601 [00468] Example 13 was prepared in a manner similar to Example 2. MS: m/z = 530.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ J = 8.4 Hz, 1H), 8.04 - 7.96 (m, 5H), 7.50 - 7.39 (m, 7H), 7.12 (dd, J = 7.6, 1.6 Hz, 1H), 7.07 (br s, 2H), 6.38 (dd, J = 8.0, 4.8 Hz, 1H), 6.24 (dd, J = 17.2, 10.0 Hz, 1H), 6.07 (dd, J = 17.2, 2.4 Hz, 1H), 5.56 (dd, J = 10.0, 2.4 Hz, 1H), 3.87 - 3.79 (m, 1H), 3.62 (d, J = 13.6 Hz, 1H), 3.54 (d, J = 13.6 Hz, 1H), 2.80 - 2.75 (m, 1H), 2.70 - 2.66 (m, 1H), 2.07 - 2.01 (m, 1H), 1.91 - 1.85 (m, 1H), 1.78 - 1.68 (m, 2H), 1.57 - 1.49 (m, 1H), 1.25 - 1.20 (m, 1H). [00469] Example 14: (R)-N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5 - b]pyridin-3-yl)benzyl)pyrrolidin-3-yl)acrylamide [00470] Example 14 was prepared in a manner similar to Example 2. MS: m/z = 516.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ - 7.37 (m, 7H), 7.14 (dd, J = 7.6, 1.6 Hz, 1H), 7.03 (br s, 2H), 6.37 (dd, J = 8.0, 5.2 Hz, 1H), 6.23 (dd, J = 17.2, 10.0 Hz, 1H), 6.07 (dd, J = 17.2, 2.4 Hz, 1H), 5.56 (dd, J = 10.0, 2.4 Hz, 1H), 4.37 - 4.13 (m, 1H), 3.68 (s, 2H), 2.71 - 2.66 (m, 2H), 2.45 - 2.37 (m, 2H), 2.22 - 2.11 (m, 1H), 1.67 - 1.57 (m, 1H). [00471] Example 15: N-(1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)azetidin-3-yl)acrylamide [00472] Example 15 was prepared in a manner similar to Example 2. MS: m/z = 502.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ J = 8.4 Hz, 1H), 8.05 - 8.02 (m, 2H), 7.98 (dd, J = 4.8, 1.6 Hz, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.52 - 7.40 (m, 7H), 7.31 (dd, J = 7.6, 2.0 Hz, 1H), 6.47 (dd, J = 7.6, 5.2 Hz, 1H), 6.26 - 6.22 (m, 2H), 5.68 (t, J = 6.0 Hz, 1H), 4.59 - 4.52 (m, 1H), 3.79 (s, 2H), 3.76 - 3.72 (m, 2H), 3.20 - 3.14 (m, 2H). [00473] Example 16: 1-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)-1,4-diazepan-1-yl)prop-2-en-1-one WSGR Docket No.62619-716.601 [00474] Example 16 was prepared in a manner similar to Example 2. MS: m/z = 530.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ 7.55 - 7.41 (m, 7H), 7.19 - 7.12 (m, 1H), 7.09 - 7.00 (m, 2H), 6.84 - 6.69 (m, 1H), 6.47 - 6.32 (m, 1H), 6.21 - 6.04 (m, 1H), 5.78 - 5.59 (m, 1H), 3.78 - 3.70 (m, 2H), 3.67 - 3.55 (m, 4H), 2.75 - 2.64 (m, 3H), 2.40 - 2.27 (m, 1H), 1.85 - 1.74 (m, 2H). [00475] Example 17: N-(7-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)-7-azaspiro[3.5]nonan-2-yl)acrylamide [00476] Example 17 was prepared in a manner similar to Example 2. MS: m/z = 570.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ J = 8.4 Hz, 1H), 8.06 - 8.01 (m, 2H), 8.00 - 7.96 (m, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.52 (d, J = 8.4 Hz, 2H), 7.46 - 7.31 (m, 6H), 6.47 (dd, J = 7.6, 5.2 Hz, 1H), 6.23 – 6.20 (m, 1H), 5.67 – 5.62 (m, 1H), 4.39 – 4.32 (m, 1H), 3.6 (s, 2H), 2.66 - 2.33 (m, 4H), 2.32 – 2.25 (m, 2H), 1.78 - 1.69 (m, 4H), 1.67 – 1.60 (m, 2H). [00477] Example 18: N-(2-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)-2-azaspiro[3.3]heptan-6-yl)acrylamide [00478] Example 18 was prepared in a manner similar to Example 2. MS: m/z = 542.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ 8.19 (d, J = 8.4 Hz, 1H), 8.03 (d, J = 6.8 Hz, 2H), 7.98 (dd, J = 4.8, 2.0 Hz, 1H), 7.95 (d, J = 8.4 Hz, 1H), 7.50 - 7.45 (m, 3H), 7.44 - 7.36 (m, 4H), 7.32 (dd, J = 7.6, 5.2 Hz, 1H), 6.48 (dd, J = 7.6, 5.2 Hz, 1H), 6.21 - 6.15 (m, 2H), 5.64 (dd, J = 7.2, 5.2 Hz, 1H), 4.26 - 4.20 (m, 1H), 3.70 (s, 2H), 3.42 (s, 4H), 2.61 - 2.52 (m, 2H), 2.19 - 2.08 (m, 2H). WSGR Docket No.62619-716.601 [00479] Example 19: N-(2-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)-2-azaspiro[3.5]nonan-7-yl)acrylamide [00480] Example 19 was prepared in a manner similar to Example 2. MS: m/z = 570.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ J = 8.4 Hz, 1H), 8.03 (d, J = 7.2 Hz, 2H), 7.98 (dd, J = 5.2, 1.6 Hz, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.53 - 7.33 (m, 8H), 6.47 (dd, J = 7.2, 4.8 Hz, 1H), 6.22 - 6.18 (m, 2H), 5.62 (dd, J = 7.2, 5.2 Hz, 1H), 3.77 (s, 2H), 3.72 - 3.67 (m, 1H), 3.19 (s, 2H), 3.13 (s, 2H), 2.03 - 1.97 (m, 2H), 1.85 - 1.78 (m, 2H), 1.61 - 1.54 (m, 2H), 1.37 - 1.31 (m, 2H). [00481] Example 20: N-(2-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)-2-azaspiro[3.5]nonan-7-yl)ethenesulfonamide [00482] Example 29 was prepared in a manner similar to Example 4. MS: m/z = 606.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4 J = 8.4 Hz, 1H), 8.01 (d, J = 7.2 Hz, 2H), 7.97 (d, J = 3.2 Hz, 1H), 7.92 ( d, J = 8.4 Hz, 1H), 7.49 - 7.33 (m, 8H), 7.29 (d, J = 6.4 Hz, 1H), 6.65 (dd, J = 16.4, 10.0 Hz, 1H), 6.44 (dd, J = 7.2, 5.2 Hz, 1H), 6.11 (d, J = 16.4 Hz, 1H), 5.89 (d, J = 10.0 Hz, 1H), 3.74 (s, 2H), 3.14 (s, 2H), 3.08 (s, 2H), 3.06 - 3.00 (m, 1H), 1.97 - 1.91 (m, 2H), 1.87 - 1.79 (m, 2H), 1.54 - 1.46 (m, 2H), 1.38 - 1.32 (m, 2H). [00483] Example 21: 1-(7-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)-2,7-diazaspiro[3.5]nonan-2-yl)prop-2-en-1-one WSGR Docket No.62619-716.601 [00484] Example 21 was prepared in a manner similar to Example 2. MS: m/z = 556.4 [M + H] ⁺ . 1H NMR (400 MHz, Methanol-d ₄ ) 8.20 (d, J = 8.4 Hz, 1H), 8.06 - 8.01 (m, 2H), 7.99 (dd, J = 4.8, 1.2 Hz, 1H), 7.95 (d, J = 8.4 Hz, 1H), 7.53(d, J = 8.4 Hz, 2H), 7.47 - 7.31 (m, 6H), 6.48 (dd, J = 7.6, 4.8 Hz, 1H), 6.35 (dd, J = 17.2, 10.4 Hz, 1H), 6.24 (dd, J = 17.2, 2.0 Hz, 1H), 5.73 (dd, J = 10.4, 2.0 Hz, 1H), 4.00 (s, 2H), 3.76 (s, 2H), 3.62 (s, 2H), 2.67 - 2.31 (m, 4H), 1.89 - 1.82 (m, 4H). [00485] Example 22: 3-(5-Phenyl-3-(4-((2-(vinylsulfonyl)-2,7-diazaspiro[3.5]nona n-7- yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-am ine [00486] Example 22 was prepared in a manner similar to Example 5. MS: m/z = 592.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6) 8.27 (d, J = 8.4 Hz, 1H), 8.04 - 7.97 (m, 4H), 7.48 - 7.39 (m, 7H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 7.09 - 7.03 (m, 1H), 7.02 (br s, 2H), 6.37 (dd, J = 7.6, 5.2 Hz, 1H), 6.28 (d, J = 10.0 Hz, 1H), 6.17 (d, J = 12.8 Hz, 1H), 3.54 - 3.53 (m, 4H), 3.31 -3.29 (m, 2H), 2.36 - 2.27 (m, 4H), 1.73 -1.63 (m, 4H). [00487] Example 23: 1-(8-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)-2,8-diazaspiro[4.5]decan-2-yl)prop-2-en-1-one [00488] Example 23 was prepared in a manner similar to Example 2. MS: m/z = 570.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4 J = 8.4 Hz, 1H), 8.02 (d, J = 8.0 Hz, 2H), 7.98 - 7.97 (m, 1H), 7.93 (d, J = 8.4 Hz, 1H), 7.38 (d, J = 8.4 Hz, 2H), 7.49 - 7.29 (m, 6H), 6.63 - 6.55 (m, 1H), 6.51 - 6.43 (m, 1H), 6.28 – 6.22 (m, 1H), 5.76 - 5.68 (m, 1H), 3.71 - 3.66 (m, 1H), 3.64 (s, 2H), 3.58 - 3.52 (m, 1H), 3.47 - 3.45 (m, 1H), 3.38 -3.37 (m, 1H), 2.72 - 2.54 (m, 2H), 2.54 - 2.41 (m, 2H), 1.90 – 1.87(m, 1H), 1.84 - 1.78 (m, 1H), 1.70 - 1.61 (m, 4H). [00489] Example 24: 3-(5-Phenyl-3-(4-((2-(vinylsulfonyl)-2,8-diazaspiro[4.5]deca n-8- yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-am ine WSGR Docket No.62619-716.601 [00490] Example 24 was prepared in a manner similar to Example 5. MS: m/z = 606.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d J = 8.4 Hz, 1H), 8.06 ( d, J = 4.0 Hz, 1H), 8.01 (d, J = 8.0 Hz, 2H), 7.81 (d, J = 8.0 Hz, 1H), 7.53 - 7.49 (m, 2H), 7.48 - 7.31 (m, 5H), 7.09 (d, J = 7.6 Hz, 1H), 6.61 (br s, 2H), 6.48 (dd, J = 16.8, 10.0 Hz, 1H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 6.26 - 6.24 (m, 1H), 6.01 (d, J = 10.0 Hz, 1H), 3.80 - 3.49 (m, 2H), 3.35 (t, J = 7.2 Hz, 2H), 3.16 (s, 2H), 2.67 - 2.54 (m, 1H), 2.47 - 2.35 (m, 1H), 1.80 ( t, J = 7.2 Hz, 2H), 1.73 - 1.65 (m, 4H), 1.48 - 1.41 (m, 2H). [00491] Example 25: 1-(9-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)-3,9-diazaspiro[5.5]undecan-3-yl)prop-2-en-1-one [00492] Example 25 was prepared in a manner similar to Example 2. MS: m/z = 584.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) J = 8.8 Hz, 1H), 8.02 (dd, J = 8.4, 1.2 Hz, 2H), 7.97 (dd, J = 4.8, 1.6 Hz, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.53 (d, J = 8.4 Hz, 2H), 7.46 - 7.29 (m, 6H), 6.74 (dd, J = 16.8, 10.8 Hz, 1H), 6.46 (dd, J = 7.6, 5.2 Hz, 1H), 6.16 (dd, J = 16.8, 2.0 Hz, 1H), 5.71 (dd, J = 10.4, 2.0 Hz, 1H), 3.64 (s, 2H), 3.60 - 3.57 (m, 2H), 3.36 - 3.34 (m, 2H), 2.52 (t, J = 4.4 Hz, 4H), 1.62 (t, J = 5.2 Hz, 4H), 1.52 - 1.51 (m,,4H). [00493] Example 26: 3-(5-Phenyl-3-(4-((9-(vinylsulfonyl)-3,9-diazaspiro[5.5]unde can-3- yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-am ine [00494] Example 26 was prepared in a manner similar to Example 4. MS: m/z = 620.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4) 8.20 (d, J = 8.4 Hz, 1H), 8.03 (d, J = 7.2 Hz, 2H), 7.98 (dd, J = 4.8, 1.6 Hz, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.55 (d, J = 8.0 Hz, 2H), 7.49 - 7.31 (m, WSGR Docket No.62619-716.601 6H), 6.64 (dd, J = 16.8, 10.0 Hz, 1H), 6.47 (dd, J = 7.6, 4.8 Hz, 1H), 6.16 (d, J = 16.8 Hz, 1H), 6.09 (d, J = 10.0 Hz, 1H), 3.74 (s, 2H), 3.15 - 3.12 (m, 4H), 2.66 - 2.54 (m, 4H), 1.64 – 1.56 (m, 8H). [00495] Example 27: 1-(6-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)-2,6-diazaspiro[3.4]octan-2-yl)prop-2-en-1-one [00496] Example 27 was prepared in a manner similar to Example 2. MS: m/z = 542.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6) J = 8.4 Hz, 1H), 8.03 (d, J = 7.2 Hz, 2H), 8.01 - 7.96 (m, 2H), 7.49 - 7.37 (m, 7H), 7.16 (dd, J = 8.4, 1.6 Hz, 1H), 7.02 (br s, 2H), 6.37 (dd, J =8.0, 4.8 Hz, 1H), 6.29 (dd, J = 17.2, 10.4 Hz, 1H), 6.14 - 6.03 (m, 1H), 5.65 (dd, J = 10.4, 2.4 Hz, 1H), 4.14 (s, 2H), 3.85 (s, 2H), 3.68 (s, 2H), 2.75 - 2.67 (m, 2H), 2.61 - 2.56 (m, 2H), 2.05 ( t, J = 7.2 Hz, 2H). [00497] Example 28: (R)-N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5 - b]pyridin-3-yl)benzyl)piperidin-3-yl)ethenesulfonamide [00498] Example 28 was prepared in a manner similar to Example 2. MS: m/z = 566.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4 J = 8.4 Hz, 1H), 8.03 (d, J = 8.0 Hz, 2H), 7.97 (d, J = 2.8 Hz, 1H), 7.93 (d, J = 8.4 Hz, 1H), 7.58 - 7.48 (m, 2H), 7.47 - 7.33 (m, 5H), 7.30 (d, J = 7.6 Hz, 1H), 6.58 (dd, J = 16.4, 10.0 Hz, 1H), 6.53 - 6.47 (m, 1H), 6.06 (d, J = 16.8 Hz, 1H), 5.82 (d, J = 10.0 Hz, 1H), 3.89 - 3.54 (m, 3H), 3.02 - 2.84 (m, 2H), 2.79 - 2.67 (m, 1H), 2.20 - 2.10 (m, 1H), 2.05 - 1.97 (m, 1H), 1.93 - 1.84 (m, 1H), 1.81 - 1.72 (m, 1H), 1.67 - 1.55 (m, 2H). [00499] Example 29: (R)-N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5 - b]pyridin-3-yl)benzyl)pyrrolidin-3-yl)ethenesulfonamide WSGR Docket No.62619-716.601 [00500] Example 29 was prepared in a manner similar to Example 4. MS: m/z = 552.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4 J = 8.4 Hz, 1H), 8.02 (d, J = 7.2 Hz, 2H), 7.98 (dd, J = 4.8, 1.6 Hz, 1H), 7.93 (d, J = 8.8 Hz, 1H), 7.53 (d, J = 8.4 Hz, 2H), 7.45 - 7.36 (m, 5H), 7.30 (dd, J = 8.0, 1.6 Hz, 1H), 6.64 (dd, J = 16.4, 10.0 Hz, 1H), 6.48 (dd, J = 7.6, 4.8 Hz, 1H), 6.14 (d, J = 16.4 Hz, 1H), 5.93 (d, J = 10.0 Hz, 1H), 3.87 - 3.80 (m, 1H), 3.79 - 3.65 (m, 2H), 2.92 - 2.83 (m, 1H), 2.77 - 2.68 (m, 1H), 2.67 - 2.57 (m, 1H), 2.56 - 2.50 (m, 1H), 2.33 - 2.19 (m, 1H), 1.82 - 1.70 (m, 1H). [00501] Example 30: 1-(7-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)-2,7-diazaspiro[4.4]nonan-2-yl)prop-2-en-1-one [00502] Example 30 was prepared in a manner similar to Example 2. MS: m/z = 556.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4 J = 8.4 Hz, 1H), 8.04 - 7.99 (m, 2H), 7.98 - 7.94 (m, 1H), 7.91 (d, J = 8.4 Hz, 1H), 7.53 (d, J = 8.0 Hz, 2H), 7.43 - 7.33 (m, 5H), 7.30 - 7.24 (m, 1H), 6.60 - 6.49 (m, 1H), 6.45 - 6.40 (m, 1H), 6.3 - 6.22 (m, 1H), 5.75 - 5.70 (m, 1H), 3.79 - 3.73 (m, 2H), 3.69 - 3.56 (m, 2H), 3.54 - 3.45 (m, 2H), 2.88 - 2.70 (m, 2H), 2.67 - 2.52 (m, 2H), 2.09 - 1.93 (m, 2H), 1.87 (t, J = 7.2 Hz, 2H). [00503] Example 31: 3-(5-Phenyl-3-(4-((7-(vinylsulfonyl)-2,7-diazaspiro[4.4]nona n-2- yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-am ine [00504] Example 31 was prepared in a manner similar to Example 4. MS: m/z = 592.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d J = 8.4 Hz, 1H), 8.07 (d, J = 3.6 Hz, 1H), 8.01 (d, J = 7.2 Hz, 2H), 7.80 (d, J = 8.4 Hz, 1H), 7.50 - 7.34 (m, 7H), 7.10 (d, J = 6.8 Hz, 1H), WSGR Docket No.62619-716.601 6.60 (br s, 2H), 6.48 - 6.33 (m, 2H), 6.21 (d, J = 16.4 Hz, 1H), 5.95 (d, J = 10.0 Hz, 1H), 3.76 - 3.65 (m, 2H), 3.42 - 3.27 (m, 3H), 3.23 - 3.17 (m, 1H), 2.78 - 2.58 (m, 3H), 2.50 - 2.44 (m, 1H), 1.98 - 1.81 (m, 4H). [00505] Example 32: 1-(2-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)-2,8-diazaspiro[4.5]decan-8-yl)prop-2-en-1-one [00506] Example 32 was prepared in a manner similar to Example 2. MS: m/z = 570.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ 8.16 (d, J = 8.0 Hz, 1H), 8.05 - 8.00 (m, 2H), 7.97 (dd, J = 5.2, 2.0 Hz, 1H), 7.93 (d, J = 8.0 Hz, 1H), 7.52 (d, J = 8.0 Hz, 2H), 7.44 - 7.30 (m, 6H), 6.75 (dd, J = 16.8, 10.4 Hz, 1H), 6.45 (dd, J = 7.6, 5.2 Hz, 1H), 6.16 (dd, J = 16.8, 2.0 Hz, 1H), 5.71 (dd, J = 10.4, 2.0 Hz, 1H), 3.71 (s, 2H), 3.58 - 3.55 (m, 2H), 3.36 - 3.34 (m, 2H), 2.72 - 2.70 (m, 2H), 2.55 - 2.49 (m, 2H), 1.75 (t, J = 6.8 Hz, 2H), 1.63 - 1.61 (m, 4H). [00507] Example 33: 3-(5-Phenyl-3-(4-((8-(vinylsulfonyl)-2,8-diazaspiro[4.5]deca n-2- yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-am ine [00508] Example 33 was prepared in a manner similar to Example 4. MS: m/z = 606.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) J = 8.4 Hz, 1H), 8.08 - 8.05 (m, 1H), 8.04 - 8.00 (m, 2H), 7.81 (d, J = 8.4 Hz, 1H), 7.68 - 7.56 (m, 2H), 7.48 - 7.42 (m, 4H), 7.41 - 7.35 (m, 1H), 7.11 (dd, J = 7.6, 1.2 Hz, 1H), 6.63 (br s, 2H), 6.44 - 6.35 (m, 2H), 6.25 - 6.18 (m, 1H), 6.01 (d, J = 10.0 Hz, 1H), 3.90 - 3.84 (m, 2H), 3.36 - 3.14 (m, 2H), 3.12 - 2.94 (m, 2H), 2.94 - 2.71 (m, 4H), 1.91 - 1.80 (m, 2H), 1.77 - 1.69 (m, 4H). [00509] Example 34: 1-(2-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)-2,7-diazaspiro[4.5]decan-7-yl)prop-2-en-1-one WSGR Docket No.62619-716.601 [00510] Example 34 was prepared in a manner similar to Example 2. MS: m/z = 570.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ 8.19 (d, J = 8.4 Hz, 1H), 8.04 (d, J = 7.2 Hz, 2H), 7.98 (d, J = 4.8 Hz, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.56 - 7.50 (m, 2H), 7.45 - 7.28 (m, 6H), 6.84 - 6.70 (m, 1H), 6.52 - 6.44 (m, 1H), 6.15 (dd, J = 17.6, 8.4 Hz, 1H), 5.79 - 5.63 (m, 1H), 3.80 - 3.70 (m, 2H), 3.59 - 3.51 (m, 2H), 3.46 - 3.35 (m, 2H), 2.95 - 2.74 (m, 1H), 2.70 - 2.61 (m, 1H), 2.58 - 2.47 (m, 1H), 2.36 - 2.13 (m, 1H), 1.76 - 1.55 (m, 6H). [00511] Example 35: 3-(5-Phenyl-3-(4-((7-(vinylsulfonyl)-2,7-diazaspiro[4.5]deca n-2- yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-am ine [00512] Example 35 was prepared in a manner similar to Example 4. MS: m/z = 606.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d) J = 8.4 Hz, 1H), 8.07 (dd, J = 4.8, 1.6 Hz, 1H), 8.01 (d, J = 8.0 Hz, 2H), 7.80 (d, J = 8.4 Hz, 1H), 7.69 - 7.55 (m, 2H), 7.47 - 7.40 (m, 4H), 7.39 - 7.35 (m, 1H), 7.11 (dd, J = 7.6, 1.6 Hz, 1H), 6.62 (br s, 2H), 6.45 - 6.35 (m, 2H), 6.27 - 6.18 (m, 1H), 6.01 (d, J = 10.0 Hz, 1H), 3.88 - 3.80 (m, 2H), 3.21 - 3.14 (m, 2H), 3.12 - 2.95 (m, 2H), 2.93 - 2.73 (m, 4H), 1.89 - 1.80 (m, 2H), 1.60 - 1.45 (m, 4H). [00513] Example 36: 1-(2-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)-2,7-diazaspiro[3.5]nonan-7-yl)prop-2-en-1-one [00514] Example 36 was prepared in a manner similar to Example 2. MS: m/z = 556.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6) 8.19 (d, J = 8.4 Hz, 1H), 8.05 - 8.01 (m, 2H), 7.98 (dd, J = 5.2, 2.0 Hz, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.52 - 7.46 (m, 3H), 7.45 - 7.40 (m, 3H), WSGR Docket No.62619-716.601 7.39 - 7.36 (m, 1H), 7.33 (dd, J = 7.6, 1.6 Hz, 1H), 6.76 (dd, J = 16.8, 10.8 Hz, 1H), 6.47 (dd, J = 7.6, 4.8 Hz, 1H), 6.16 (dd, J = 16.8, 2.0 Hz, 1H), 5.72 (dd, J = 10.8, 2.0 Hz, 1H), 3.80 (s, 2H), 3.61 - 3.55 (m, 4H), 3.25 (s, 4H), 1.84 - 1.77 (m, 4H). [00515] Example 37: (R)-1-(7-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5 - b]pyridin-3-yl)benzyl)-2,7-diazaspiro[4.4]nonan-2-yl)prop-2- en-1-one [00516] Example 37 was prepared in a manner similar to Example 2. MS: m/z = 556.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6) 8.27 (d, J = 8.4 Hz, 1H), 8.06 - 7.95 (m, 4H), 7.52 - 7.36 (m, 7H), 7.17 - 7.11 (m, 1H), 7.02 (br s, 2H), 6.60 – 6.52 (m, 1H), 6.35 (dd, J = 7.6, 4.8 Hz, 1H), 6.17 - 6.07 (m, 1H), 5.69 - 5.60 (m, 1H), 3.68 (s, 2H), 3.62 - 3.48 (m, 2H), 3.45- 3.40 (m, 2H), 2.71 - 2.65 (m, 1H), 2.60 - 2.54 (m, 2H), 2.44 - 2.38 (m, 1H), 1.97 - 1.73 (m, 4H). [00517] Example 38: 1-(9-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)-2,9-diazaspiro[5.5]undecan-2-yl)prop-2-en-1-one [00518] Example 38 was prepared in a manner similar to Example 2. MS: m/z = 584.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) 8.27 (d, J = 8.4 Hz, 1H), 8.04 - 7.97 (m, 4H), 7.48 - 7.38 (m, 7H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 7.03 (br s, 2H), 6.86 - 6.75 (m, 1H), 6.43 - 6.32 (m, 1H), 6.16 - 6.02 (m, 1H), 5.66 - 5.56 (m, 1H), 3.57 (s, 2H), 3.51 - 3.46 (m, 2H), 3.44 - 3.40 (m, 1H), 3.35 - 3.33 (m, 1H), 2.40 - 2.30 (m, 4H), 1.51 - 1.34 (m, 8H). [00519] Example 39: 1-((2S,6S)-4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo [4,5- b]pyridin-3-yl)benzyl)-2,6-dimethylpiperazin-1-yl)prop-2-en- 1-one WSGR Docket No.62619-716.601 [00520] Example 39 was prepared in a manner similar to Example 2. MS: m/z = 544.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) 8.27 (d, J = 8.4 Hz, 1H), 8.04 - 7.98 (m, 4H), 7.51 - 7.43 (m, 6H), 7.41 - 7.38 (m, 1H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.04 (br s, 2H), 6.74 (dd, J = 16.4, 10.4 Hz, 1H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 6.09 (dd, J = 16.4, 2.0 Hz, 1H), 5.63 (dd, J = 10.4, 2.0 Hz, 1H), 4.02 - 3.94 (m, 2H), 3.74 (d, J = 13.6 Hz, 1H), 3.57 (d, J = 13.6 Hz, 1H), 2.73 - 2.67 (m, 2H), 2.39 - 2.32 (m, 2H), 1.24 (d, J = 6.4 Hz, 6H). [00521] Example 40: 1-((2R,6R)-4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo [4,5- b]pyridin-3-yl)benzyl)-2,6-dimethylpiperazin-1-yl)prop-2-en- 1-one [00522] Example 40 was prepared in a manner similar to Example 2. MS: m/z = 544.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6) 8.27 (d, J = 8.4 Hz, 1H), 8.11 - 7.94 (m, 4H), 7.58 - 7.34 (m, 7H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.05 (br s, 2H), 6.74 (dd, J = 16.8, 10.4 Hz, 1H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 6.09 (dd, J = 16.8, 2.4 Hz, 1H), 5.63 (dd, J = 10.4, 2.4 Hz, 1H), 3.98 (br s, 2H), 3.74 (d, J = 13.6 Hz, 1H), 3.57 (d, J = 13.6 Hz, 1H), 2.77 - 2.64 (m, 2H), 2.44 - 2.30 (m, 2H), 1.24 (d, J = 6.4 Hz, 6H). [00523] Example 41: (R)-1-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5 -b]pyridin- 3-yl)benzyl)-2-methylpiperazin-1-yl)prop-2-en-1-one [00524] Example 41 was prepared in a manner similar to Example 2. MS: m/z = 530.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ J = 8.4 Hz, 1H), 8.06 - 7.97 (m, 4H), 7.53 - 7.44 (m, 6H), 7.42 - 7.37 (m, 1H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.05 (br s, 2H), 6.78 (dd, J = 16.8, 10.4 Hz, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 6.10 (dd, J = 16.8, 2.4 Hz, 1H), 5.67 (dd, J = 10.4, 2.4 Hz, 1H), 4.70 - 4.46 (m, 0.5H), 4.42 - 4.17 (m, 1H), 4.02 - 3.82 (m, 0.5H), 3.66 (d, J = 13.6 Hz, 1H), 3.52 (d, J = 13.6 Hz, 1H), 3.14 - 2.89 (m, 1H), 2.88 - 2.79 (m, 1H), 2.68 - 2.63 (m, 1H), 2.17 - 2.05 (m, 1H), 2.03 - 1.92 (m, 1H), 1.23 (d, J = 6.0 Hz, 3H) [00525] Example 42: 1-(3-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)prop-2-en-1-one WSGR Docket No.62619-716.601 [00526] Example 42 was prepared in a manner similar to Example 3. MS: m/z = 542.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ J = 8.4 Hz, H), 8.04 – 7.97 (m, 4H), 7.50 - 7.44 (m, 6H), 7.42 - 7.38 (m, 1H), 7.11 (dd, J = 7.6, 1.6 Hz, 1H), 7.05 (br s, 2H), 6.70 (dd, J = 16.8, 10.4 Hz, 1H), 6.37 (dd, J = 8.0, 4.8 Hz, 1H), 6.16 (dd, J = 16.8, 2.4 Hz, 1H), 5.67 (dd, J = 10.4, 2.4 Hz, 1H), 4.55 - 4.45 (m, 1H), 3.59 (s, 2H), 2.75 - 2.65 (m, 2H), 2.23 (d, J = 10.4 Hz, 1H), 2.13 (d, J = 10.4 Hz, 1H), 1.96 – 1.81 (m, 4H). [00527] Example 43: 1-(8-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)prop-2-en-1-one [00528] Example 43 was prepared in a manner similar to Example 3. MS: m/z = 542.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 J = 8.4 Hz, H), 8.04 – 7.97 (m, 4H), 7.57 (d, J = 8.0 Hz, H), 7.52 - 7.44 (m, 4H), 7.42 - 7.38 (m, 1H), 7.17 (dd, J = 7.6, 1.6 Hz, 1H), 7.01 (br s, 2H), 6.75 (dd, J = 16.8, 10.4 Hz, 1H), 6.40 (dd, J = 8.0, 4.8 Hz, 1H), 6.10 (dd, J = 16.8, 2.4 Hz, 1H), 5.66 (dd, J = 10.4, 2.4 Hz, 1H), 4.10 (d, J = 11.2 Hz, 1H), 3.75 (d, J = 13.6 Hz, 1H), 3.63 (s, 2H), 3.30 – 3.28 (m, 1H), 3.25 – 3.20 (m, 2H), 2.85 (d, J = 11.2 Hz, 1H), 2.00 – 1.95 (m, 2H), 1.52 – 1.45 (m, 2H). [00529] Example 44: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)azepan-4-yl)acrylamide [00530] Example 44 was prepared in a manner similar to Example 2. MS: m/z = 544.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ J = 8.4 Hz, 1H), 8.09 - 7.94 (m, 5H), WSGR Docket No.62619-716.601 7.54 - 7.35 (m, 7H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 7.04 (br s, 2H), 6.36 (dd, J = 7.6, 4.8 Hz, 1H), 6.26 - 6.16 (m, 1H), 6.10 - 6.02 (m, 1H), 5.54 (dd, J = 10.0, 2.4 Hz, 1H), 4.00 - 3.86 (m, 1H), 3.75 - 3.63 (m, 2H), 2.68 - 2.62 (m, 2H), 2.59 - 2.52 (m, 2H), 1.90 - 1.78 (m, 2H), 1.75 - 1.54 (m, 4H). [00531] Example 45: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)azepan-3-yl)acrylamide [00532] Example 45 was prepared in a manner similar to Example 2. MS: m/z = 544.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4) 8.19 (d, J = 8.4 Hz, 1H), 8.04 (d, J = 7.2 Hz, 2H), 7.98 - 7.92 (m, 2H), 7.57 (d, J = 8.4 Hz, 2H), 7.45 - 7.41 (m, 4H), 7.39 - 7.35 (m, 1H), 7.25 (dd, J = 7.6, 2.4 Hz, 1H), 6.46 (dd, J = 7.6, 4.8 Hz, 1H), 6.25 - 6.17 (m, 1H), 6.15 - 6.09 (m, 1H), 5.53 (dd, J = 9.6, 2.0 Hz, 1H), 4.11 - 4.02 (m, 1H), 3.82 (d, J = 10.0 Hz, 1H), 3.74 (d, J = 10.0 Hz, 1H), 2.90 - 2.84 (m, 1H), 2.83 - 2.77 (m, 1H), 2.74 - 2.66 (m, 2H), 1.95 - 1.88 (m, 1H), 1.80 - 1.72 (m, 3H), 1.70 - 1.62 (m, 2H). [00533] Example 46: 1-(7-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)-4,7-diazaspiro[2.5]octan-4-yl)prop-2-en-1-one [00534] Example 46 was prepared in a manner similar to Example 2. MS: m/z = 542.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 J = 8.4 Hz, 1H), 8.11 - 7.93 (m, 4H), 7.49 - 7.43 (m, 6H), 7.42 - 7.37 (m, 1H), 7.12 (dd, J = 8.0, 2.0 Hz, 1H), 7.05 (br s, 2H), 6.95 - 6.78 (m, 1H), 6.35 (dd, J = 7.6, 4.8 Hz, 1H), 6.13 (dd, J = 16.8, 2.0 Hz, 1H), 5.70 (d, J = 10.8 Hz, 1H), 3.59 (br s, 2H), 2.55 - 2.53 (m, 2H), 2.36 - 1.96 (m, 4H), 1.10 - 0.61 (m, 4H). [00535] Example 47: (S)-1-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5 -b]pyridin- 3-yl)benzyl)-2-methylpiperazin-1-yl)prop-2-en-1-one WSGR Docket No.62619-716.601 [00536] To a solution of Intermediate 33 (45 mg, 94.6 µmol) in THF (1.5 mL) were added K ₂ CO ₃ (39.2 mg, 284 µmol) and acryloyl chloride (9.42 mg, 104 µmol, 8.49 µL). The reaction mixture was stirred at 0 °C for 1 hr. Water (5 mL) was added at 0 °C slowly and extracted with EtOAc (10 mL x 2). The combined organic layers were washed with brine (10 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. The residue was purified by prep-HPLC (column: Phenomenex C1880 * 40 mm 3 µm; mobile phase: [water (NH4HCO3) - ACN]; B%: 52% - 82%, 8 min), (S)-1-(4-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5 -b]pyridin-3- yl)benzyl)-2-methylpiperazin-1-yl)prop-2-en-1-one (Example 47, 5.9 mg, yield: 12%) as a yellow solid. MS: m/z = 530.2 [M + H] ⁺ . ¹ H NMR (400MHz, Acetonitrile-d3 J = 8.4 Hz, 1H), 8.05 - 7.99 (m, 3H), 7.90 (d, J = 8.4 Hz, 1H), 7.54 (d, J = 8.4 Hz, 2H), 7.50 - 7.36 (m, 5H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 6.75 - 6.54 (m, 3H), 6.38 (dd, J = 8.0, 4.8 Hz, 1H), 6.17 - 6.09 (m, 1H), 5.64 (dd, J = 10.8, 2.4 Hz, 1H), 3.69 - 3.49 (m, 2H), 2.94 – 2.84 (m, 1H), 2.75 - 2.67 (m, 1H), 2.15 - 2.00 (m, 5H), 1.31 – 1.27 (m, 3H). [00537] Example 48: 1-((1S,4S)-5-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo [4,5- b]pyridin-3-yl)benzyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)pr op-2-en-1-one [00538] Example 48 was prepared in a manner similar to Example 3. MS: m/z = 528.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6) 8.19 (d, J = 8.4 Hz, 1H), 8.02 (d, J = 8.0 Hz, 2H), 7.99 - 7.89 (m, 2H), 7.60 - 7.50 (m, 2H), 7.45 - 7.35 (m, 5H), 7.33 - 7.27 (m, 1H), 6.72 - 6.49 (m, 1H), 6.49 - 6.43 (m, 1H), 6.32 - 6.26 (m, 1H), 5.805.72 (m, 1H), 4.85 - 4.57 (m, 2H), 3.80 - 3.72 (m, 2H), 3.68 - 3.65 (m, 1H), 3.55 - 3.34 (m, 1H), 3.04 - 2.90 (m, 1H), 2.78 - 2.65 (m, 1H), 2.10 - 1.98 (m, 1H), 1.88 - 1.73 (m, 1H). [00539] Example 49: 1-((1R,4R)-5-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo [4,5- b]pyridin-3-yl)benzyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)pr op-2-en-1-one WSGR Docket No.62619-716.601 [00540] Example 49 was prepared in a manner similar to Example 2. MS: m/z = 528.2 [M + H] ⁺ . 1H NMR (400 MHz, Dimethylsulfoxide-d6 J = 8.4 Hz, 1H), 8.00 - 7.94 (m, 4H), 7.48 - 7.34 (m, 6H), 7.13 (d, J = 8.0 Hz, 1H), 6.97 (br s, 2H), 6.69 - 6.72 - 6.40 (m, 1H), 6.35 (dd, J = 7.6, 4.8 Hz, 1H), 6.18 - 6.05 (m, 1H), 5.70 - 5.58 (m, 1H), 4.68 - 4.55 (m, 1H), 3.82 - 3.75 (m, 2H), 3.72 - 3.55 (m, 1H), 3.54 - 3.45 (m, 1H), 3.28 - 3.27 (m, 2H), 3.25 - 3.20 (m, 1H), 2.90 - 2.80 (m, 1H), 1.95 - 1.80 (m, 1H), 1.75 - 1.60 (m, 1H). [00541] Example 50: N-(4-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)-1,4-oxazepan-6-yl)acrylamide [00542] Step 1: tert-Butyl 6-acrylamido-1,4-oxazepane-4-carboxylate [00543] To a solution of tert-butyl 6-amino-1,4-oxazepane-4-carboxylate (100 mg, 462 µmol) and TEA (94 mg, 925 µmol) in CH ₂ Cl ₂ (2 mL) was added dropwise acryloyl chloride (42 mg, 462 µmol) at 0 °C. The resulting mixture was stirred at 0 °C for 1hr. The reaction mixture was concentrated under reduced pressure to give tert-butyl 6-acrylamido-1,4-oxazepane-4- carboxylate (125 mg, yield: 100%) as a white solid. Compound 5 directly used to the next without further purification. [00544] Step 2: N-(1,4-Oxazepan-6-yl)acrylamide [00545] To a solution of tert-butyl 6-acetamido-1,4-oxazepane-4-carboxylate (124 mg, 459 µmol) in HCl in 1,4-dioxane (2 mL). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was concentrated under reduced pressure to remove solvent to give N-(1,4-oxazepan-6- yl)acetamide (79 mg, HCl salt, yield: 83%) as a white solid. [00546] Step 3: N-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)-1,4-oxazepan-6-yl)acrylamide WSGR Docket No.62619-716.601 [00547] To a solution of Intermediate 4 (120 mg, 291 µmol) and N-(1,4-oxazepan-6- yl)acrylamide (60 mg, 350 µmol) in DMF (3 mL) was added NaI (5 mg, 29 µmol) and K ₂ CO ₃ (81 mg, 583 µmol). The mixture was stirred at 80 °C for 16 hr. The reaction mixture was quenched with H2O (30 mL) at 25 °C and extracted with EtOAc (30 mL × 2). The combined organic layers were washed with brine (30 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure to give a residue. The residue was purified by prep-TLC (CH2Cl2: MeOH = 10 : 1), N-(4-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)-1,4-oxazepan-6-yl)acrylamide (60 mg crude) was obtained as a light yellow solid. The 60 mg of crude product was purified by prep-HPLC (column: Phenomenex C18150*25 mm 10 µm; mobile phase: [water (NH4HCO3) - ACN]; B%: 32% - 62%, 14 min), N-(4-(4-(2-(2- aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyridin-3-yl)be nzyl)-1,4-oxazepan-6- yl)acrylamide (Example 50, 5.7 mg, yield: 3.6%) was obtained as a light-yellow solid. MS: m/z = 546.5 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4 J = 8.4 Hz, 1H), 8.03 (d, J = 7.6 Hz, 2H), 7.96 (dd, J = 5.2, 1.6 Hz, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.59 (d, J = 8.0 Hz, 2H), 7.44 - 7.40 (m, 4H), 7.39 - 7.36 (m, 1H), 7.26 (dd, J = 7.6, 1.6 Hz, 1H), 6.47 (dd, J = 7.6, 5.2 Hz, 1H), 6.31 - 6.23 (m, 1H), 6.18 - 6.13 (m, 1H), 5.58 (dd, J = 10.0, 2.0 Hz, 1H), 4.25 - 4.21 (m, 1H), 3.99 (dd, J = 12.8, 5.2 Hz, 1H), 3.88 - 3.83 (m, 1H), 3.80 - 3.76 (m, 3H), 3.73 - 3.69 (m, 1H), 2.97 - 2.84 (m, 2H), 2.80 - 2.74 (m, 2H). [00548] Example 51: (S)-3-(3-(4-((3-Methyl-4-(vinylsulfonyl)piperazin-1-yl)methy l)phenyl)-5- phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00549] Example 51 was prepared in a manner similar to Example 4. MS: m/z = 566.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) J = 8.4 Hz, 1H), 8.07 - 7.95 (m, 4H), 7.52 - 7.44 (m, 6H), 7.42 - 7.37 (m, 1H), 7.15 (dd, J = 8.0, 2.0 Hz, 1H), 7.03 (br s, 2H), 6.82 (dd, J = 16.4, 10.0 Hz, 1H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 6.11 - 5.98 (m, 2H), 3.96 - 3.84 (m, 1H), 3.65 (d, J = 13.6 Hz, 2H), 3.51 (d, J = 13.6 Hz, 1H), 3.20 - 3.18 (m, 1H), 2.82 - 2.79 (m, 1H), 2.62 - 2.56 (m, 2H), 2.23 - 2.18 (m, 1H), 2.14 - 2.07 (m, 1H), 1.25 (d, J = 6.4 Hz, 4H). [00550] Example 52: 3-(5-Phenyl-3-(4-((4-(vinylsulfonyl)-4,7-diazaspiro[2.5]octa n-7- yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-am ine WSGR Docket No.62619-716.601 [00551] Example 52 was prepared in a manner similar to Example 4. MS: m/z = 578.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 J = 8.4 Hz, 1H), 8.07 - 7.95 (m, 4H), 7.52 - 7.34 (m, 7H), 7.15 (dd, J = 8.0, 2.0 Hz, 1H), 7.03 (br s, 2H), 6.82 (dd, J = 16.4, 10.0 Hz, 1H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 6.11 - 5.98 (m, 2H), 3.60 (s, 2H), 3.56 – 3.48 (m, 1H), 3.25 – 3.17 (m, 1H), 2.48 - 2.38 (m, 2H), 2.33 - 2.25 (m, 2H), 1.11 – 1.01 (m, 2H), 0.70 – 0.60 (m, 2H). [00552] Example 53: 1-(5-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)prop-2-en-1-one [00553] Example 53 was prepared in a manner similar to Example 2. MS: m/z = 542.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 J = 8.4 Hz, 1H), 8.05 - 7.96 (m, 4H), 7.53 - 7.37 (m, 7H), 7.16 (dd, J = 7.6, 2.0 Hz, 1H), 7.01 (br s, 2H), 6.79 - 6.56 (m, 1H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 6.22 - 6.07 (m, 1H), 5.76 - 5.56 (m, 1H), 4.43 - 4.11 (m, 1H), 3.99 - 3.68 (m, 3H), 3.58 - 3.43 (m, 1H), 2.95 - 2.93 (m, 1H), 2.89 - 2.79 (m, 2H), 2.10 - 1.98 (m, 1H), 1.84 - 1.71 (m, 2H), 1.69 - 1.53 (m, 1H). [00554] Example 54: 1-((2S,6R)-4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo [4,5- b]pyridin-3-yl)benzyl)-2,6-dimethylpiperazin-1-yl)prop-2-en- 1-one [00555] Example 54 was prepared in a manner similar to Example 2. MS: m/z = 544.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) 8.19 (d, J = 8.8 Hz, 1H), 8.04 (d, J = 7.2 Hz, 2H), 7.98 (dd, J = 5.2, 1.6 Hz, 1H), 7.95 (d, J = 8.4 Hz, 1H), 7.59 (d, J = 8.0 Hz, 2H), 7.46 - 7.36 (m, 5H), 7.33 (dd, J = 7.6, 1.6 Hz, 1H), 6.79 (dd, J = 16.8, 10.8 Hz, 1H), 6.48 (dd, J = 7.6, 4.8 Hz, 1H), WSGR Docket No.62619-716.601 6.23 (dd, J = 16.8, 2.0 Hz, 1H), 5.74 (dd, J = 10.8, 2.0 Hz, 1H), 4.60 (s, 2H), 3.63 (s, 2H), 2.81 - 2.78 (m, 2H), 2.30 - 2.20 (m, 2H), 1.39 (d, J = 6.4 Hz, 6H). [00556] Example 55: 1-(2-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)-2,6-diazaspiro[3.4]octan-6-yl)prop-2-en-1-one [00557] Example 55 was prepared in a manner similar to Example 2. MS: m/z = 542.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 J = 8.4 Hz, 1H), 8.06 - 7.94 (m, 4H), 7.50 - 7.36 (m, 7H), 7.17 (dd, J = 7.6, 1.6 Hz, 1H), 7.00 (br s, 2H), 6.62 - 6.50 (m, 1H), 6.44 - 6.36 (m, 1H), 6.17 - 6.08 (m, 1H), 5.66 (dd, J = 10.0, 2.0 Hz, 1H), 3.69 (s, 2H), 3.58 - 3.47 (m, 2H), 3.41 - 3.36 (m, 2H), 3.21 - 3.14 (m, 4H), 2.11 (t, J = 6.8 Hz, 1H), 2.00 (t, J = 6.8 Hz, 1H). [00558] Example 56: 3-(5-Phenyl-3-(4-((6-(vinylsulfonyl)-2,6-diazaspiro[3.4]octa n-2- yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-am ine [00559] Example 56 was prepared in a manner similar to Example 4. MS: m/z = 578.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ J = 8.4 Hz, 1H), 8.08 - 7.95 (m, 4H), 7.51 - 7.37 (m, 7H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.00 (br s, 2H), 6.88 (dd, J = 16.4, 10.0 Hz, 1H), 6.40 (dd, J = 7.6, 4.8 Hz, 1H), 6.15 - 6.08 (m, 2H), 3.66 (s, 2H), 3.30 (s, 2H), 3.21 - 3.17 (m, 2H), 3.15 (s, 4H), 2.04 (t, J = 6.8 Hz, 2H). [00560] Example 57: 1-(2-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)-2,6-diazaspiro[3.5]nonan-6-yl)prop-2-en-1-one [00561] Example 57 was prepared in a manner similar to Example 2. MS: m/z = 556.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 J = 8.4 Hz, 1H), 8.02 - 7.96 (m, 4H), WSGR Docket No.62619-716.601 7.47- 7.42 (m, 7H), 7.15 (dd, J = 7.6, 2.0 Hz, 1H), 7.00 (br s, 2H), 6.92 - 6.75 (m, 1H), 6.40 – 6.34 (m, 1H), 6.15 - 6.05 (m, 1H), 5.72 - 5.63 (m, 1H), 3.70 - 3.63 (m, 4H), 3.48 - 3.40 (m, 2H), 3.05 - 3.00 (m, 2H), 2.83 – 2.82 (m, 2H), 1.78 - 1.70 (m, 2H), 1.50 - 1.40 (m, 2H). [00562] Example 58 and 59: N-((5r, 8r)-2-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-2-azaspiro[4.5]decan-8-yl )acrylamide and N-((5s, 8s)-2-(4- (2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyridin-3 -yl)benzyl)-2- azaspiro[4.5]decan-8-yl)acrylamide [00563] Example 12 was separated by SFC (column: DAICEL CHIRALPAK IG (250 mm * 30 mm, 10 µm); mobile phase: [CO ₂ - ACN/EtOH (0.1% NH ₃ H ₂ O)]; B%: 60% - 60%, A4; 26 min), N-((5r, 8r)-2-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b] pyridin-3-yl)benzyl)-2- azaspiro[4.5]decan-8-yl)acrylamide (Example 58, 24 mg, yield: 12.7%, ee: 100%) and N-((5s, 8s)-2-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b] pyridin-3-yl)benzyl)-2- azaspiro[4.5]decan-8-yl)acrylamide (Example 59, 8 mg, yield: 4.2%, ee: 99.0%) were obtained as off-white solid. Example 58: MS: m/z = 584.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ 8.27 (d, J = 8.4 Hz, 1H), 8.05 - 8.01 (m, 2H), 8.00 - 7.97 (m, 2H), 7.89 (d, J = 8.0 Hz, 1H), 7.50 - 7.43 (m, 6H), 7.39 - 7.35 (m, 1H), 7.17 (dd, J = 7.6, 1.6 Hz, 1H), 7.02 (br s, 2H), 6.38 (dd, J = 8.0, 4.8 Hz, 1H), 6.20 - 6.10 (m, 1H), 6.07 - 6.01 (m, 1H), 5.56 - 5.50 (m, 1H), 3.67 (s, 2H), 3.62 - 3.56 (m, 1H), 2.56 (t, J = 6.8 Hz, 2H), 2.37 (s, 2H), 1.78 - 1.68 (m, 2H), 1.67 - 1.63 (m, 2H), 1.57 – 1.54 (m, 2H), 1.39 - 1.32 (m, 2H), 1.24 - 1.21 (m, 1H), 1.19 – 1.16 (m, 1H). Example 59: MS: m/z = 584.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ 8.20 (d, J = 8.4 Hz, 1H), 8.05 - 8.01 (m, 2H), 8.00 - 7.97 (m, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.56 (d, J = 8.4 Hz, 2H), 7.48 - 7.35 (m, 5H), 7.33 (dd, J = 7.6, 1.6 Hz, 1H), 6.48 (dd, J = 7.6, 5.2 Hz, 1H), 6.24 - 6.18 (m, 2H), 5.62 (dd, J = 7.6, 4.4 Hz, 1H), 3.76 (s, 2H), 3.75 - 3.51 (m, 1H), 2.85 – 2.71 (m, 2H), 2.58 – 2.46 (m, 2H), 1.85 - 1.71 (m, 6H), 1.53 - 1.36 (m, 4H). [00564] Example 60 and 61: (S)-N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5 - b]pyridin-3-yl)benzyl)azepan-4-yl)acrylamide and (R)-N-(1-(4-(2-(2-Aminopyridin-3-yl)-5- phenyl-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)azepan-4-yl)acry lamide WSGR Docket No.62619-716.601 [00565] Example 44 was separated by SFC (column: DAICEL CHIRALPAK AS (250 mm * 30 mm, 10 µm); mobile phase: [0.1% NH ₃ H ₂ O MeOH]; B%: 40% - 40%, A5; 40 min), (S)-N-(1-(4- (2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyridin-3 -yl)benzyl)azepan-4- yl)acrylamide (Example 60, 30.6 mg, yield: 20.3%, ee: 100%) and (R)-N-(1-(4-(2-(2- aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyridin-3-yl)be nzyl)azepan-4-yl)acrylamide (Example 61, 50 mg crude, yield: 31%, ee: 97.0%) were obtained as yellow solid. Example 61 (50 mg crude) was purified again by prep-TLC (CH ₂ Cl ₂ : MeOH = 10:1) to give (R)-N-(1-(4-(2- (2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyridin-3-yl )benzyl)azepan-4-yl)acrylamide (Example 61, 20.3 mg, ee: 98.9%) was obtained as a light-yellow solid. Spectra for Example 60: MS: m/z = 544.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ J = 8.4 Hz, 1H), 8.09 - 7.91 (m, 4H), 7.57 (d, J = 8.0 Hz, 2H), 7.50 - 7.29 (m, 6H), 6.47 (dd, J = 7.6, 5.2 Hz, 1H), 6.27 - 6.17 (m, 2H), 5.67 - 5.58 (m, 1H), 4.14 - 4.01 (m, 1H), 3.77 (s, 2H), 2.91 - 2.63 (m, 4H), 2.03 - 1.93 (m, 2H), 1.85 - 1.63 (m, 4H). Spectra for Example 61: MS: m/z = 544.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ J = 4.8, 1.2 Hz, 1H), 7.90 - 7.86 (m, 1H), 7.52 (d, J = 8.4 Hz, 2H), 7.43 - 7.30 (m, 5H), 7.28 - 7.22 (m, 1H), 6.47 - 6.35 (m, 1H), 6.22 - 6.14 (m, 2H), 5.59 (dd, J = 8.0, 4.0 Hz, 1H), 4.07 - 3.99 (m, 1H), 3.82 (s, 2H), 2.91 - 2.70 (m, 4H), 2.00 - 1.90 (m, 2H), 1.81 - 1.62 (m, 4H). [00566] Example 62: (S)-1-(7-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5 - b]pyridin-3-yl)benzyl)-2,7-diazaspiro[4.4]nonan-2-yl)prop-2- en-1-one [00567] Example 62 was prepared in a manner similar to Example 2. MS: m/z = 556.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) 8.18 (d, J = 8.4 Hz, 1H), 8.02 (d, J = 6.8 Hz, 2H), 7.98 - 7.95 (m, 1H), 7.93 (d, J = 8.0 Hz, 1H), 7.54 (d, J = 8.0 Hz, 2H), 7.45 - 7.35 (m, 5H), 7.32 - 7.28 (m, 1H), 6.63 - 6.52 (m, 1H), 6.47 - 6.43 (m, 1H), 6.30 - 6.20 (m, 1H), 5.76 - 5.68 (m, 1H), 3.80 - 3.46 (m, 6H), 2.81 - 2.50 (m, 4H), 2.06 - 1.92 (m, 2H), 1.91 - 1.86 (m, 2H). WSGR Docket No.62619-716.601 [00568] Example 63: (E)-N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5 - b]pyridin-3-yl)benzyl)piperidin-4-yl)-4-methoxybut-2-enamide [00569] Example 63 was prepared in a manner similar to Example 7. MS: m/z = 574.5 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) 8.27 (d, J = 8.4 Hz, 1H), 8.04 - 7.94 (m, 5H), 7.49 - 7.40 (m, 7H), 7.16 (dd, J = 7.6, 2.0 Hz, 1H), 7.03 (br s, 2H), 6.62 - 6.55 (m, 1H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 6.09 (d, J = 15.6 Hz, 1H), 4.02 (dd, J = 4.0, 2.0 Hz, 2H), 3.66 - 3.59 (m, 1H), 3.56 (s, 2H), 3.28 (s, 3H), 2.82 - 2.76 (m, 2H), 2.13 - 2.04 (m, 2H), 1.79 - 1.72 (m, 2H), 1.48 - 1.39 (m, 2H). [00570] Example 64: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)piperidin-4-yl)methacrylamide [00571] CH ₂ Cl ₂ was stirred at 0 °C for 2 hr. The reaction mixture was diluted with H ₂ O (10 mL) and extracted with CH2Cl2 (15 mL × 2). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by prep-HPLC (column: [water (NH ₄ HCO ₃ ) - ACN]; B%: 35% - 65%, 15 min), N-(1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)methacrylam ide (Example 64, 96.1 mg, yield: 41%) was obtained as a light-yellow solid. MS: m/z = 544.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) J = 8.8 Hz, 1H), 8.06 - 8.01 (m, 2H), 7.98 (dd, J = 5.2, 1.6 Hz, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.54 (d, J = 8.4 Hz, 2H), 7.47 - 7.30 (m, 6H), 6.47 (dd, J = 7.6, 5.2 Hz, 1H), 5.65 (s, 1H), 5.36 (s, 1H), 3.82 - 3.70 (m, 1H), 3.64 (s, 2H), 3.01 - 2.97 (m, 2H), 2.24 - 2.16 (m, 2H), 1.93 (s, 3H), 1.91 - 1.84 (m, 2H), 1.70 - 1.57 (m, 2H). [00572] Example 65: N-(3-(3-(4-((4-Acryloyl-4,7-diazaspiro[2.5]octan-7-yl)methyl )phenyl)-5- phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-yl)acrylamide WSGR Docket No.62619-716.601 [00573] Example 65 was prepared in a manner similar to Example 2. MS: m/z = 596.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4 J = 6.0 Hz, 1H), 8.41 - 8.33 (m, 1H), 8.25 - 8.20 (m, 1H), 8.07 - 8.02 (m, 3H), 7.86 - 7.83 (m, 3H), 7.78 - 7.72 (m, 2H), 7.50 - 7.46 (m, 2H), 7.45 - 7.42 (m, 2H), 6.90 - 6.82 (m, 1H), 6.32 (dd, J = 12.8, 2.0 Hz, 1H), 5.85 - 5.82 (m, 1H), 4.99 - 4.95 (m, 2H), 4.62 - 4.58 (m, 1H), 4.51 (s, 2H), 3.72 - 3.65 (m, 1H), 3.61 - 3.56 (m, 1H), 3.15 - 3.10 (m, 2H), 2.97 - 2.88 (m, 1H), 1.61 - 1.40 (m, 2H), 1.15 - 0.96 (m, 2H). [00574] Example 66 and 67: 1-((1R,4R)-5-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-2,5-diazabicyclo[2.2.2]oc tan-2-yl)prop-2-en-1-one and 1- ((1S,4S)-5-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4 ,5-b]pyridin-3-yl)benzyl)-2,5- diazabicyclo[2.2.2]octan-2-yl)prop-2-en-1-one [00575] Example 38 was separated by SFC (column: Daicel Chiralpak AD(250 mm * 30 mm, 10 µm);mobile phase: [ACN/MeOH (0.1% NH ₃ H ₂ O)]; B%: 40% - 40%, A 5.8; 60 min), 1- ((1R,4R)-5-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4 ,5-b]pyridin-3-yl)benzyl)-2,5- diazabicyclo[2.2.2]octan-2-yl)prop-2-en-1-one (Example 66, 28.4 mg, yield: 9%, ee: 98.4%) and 1-((1S,4S)-5-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo [4,5-b]pyridin-3-yl)benzyl)-2,5- diazabicyclo[2.2.2]octan-2-yl)prop-2-en-1-one (Example 67, 50 mg crude) were obtained as yellow solid. The Example 67 (50 mg crude) was purified again by prep-TLC (CH2Cl2 : MeOH = 10 : 1) to give 1-((1S,4S)-5-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo [4,5-b]pyridin- 3-yl)benzyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)prop-2-en-1-o ne (Example 67, 17.1 mg, yield: 5.4%, ee: 98.9%) was obtained as a yellow solid. Example 66: MS: m/z = 542.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ 8.18 (d, J = 8.4 Hz, 1H), 8.03 (d, J = 7.2 Hz, 2H), 7.98 (dd, J = 5.2, 2.0 Hz, 1H), 7.93 (d, J = 8.4 Hz, 1H), 7.57 (d, J = 8.4 Hz, 2H), 7.47 - 7.40 (m, 4H), 7.39 - 7.35 (m, 1H), 7.33 - 7.28 (m, 1H), 6.76 – 6.61 (m, 1H), 6.50 -6.44 (m, 1H), 6.35 - 6.20 (m, 1H), 5.82 - 5.69 (m, 1H), 4.53 - 4.15 (m, 1H), 4.13 - 3.89 (m, 1H), 3.89 - 3.74 (m, 2H), 3.65 - 3.44 (m, 1H), 3.06 - 2.95 (m, 3H), 2.25 - 2.15 (m, 1H), 1.97 - 1.87 (m, 2H), 1.75 - 1.65 (m, 1H). WSGR Docket No.62619-716.601 Example 67: MS: m/z = 542.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4 J = 8.4 Hz, 1H), 8.04 (d, J = 7.2 Hz, 2H), 7.99 (dd, J = 5.2, 2.0 Hz, 1H), 7.93 (d, J = 8.4 Hz, 1H), 7.57 (d, J = 8.4 Hz, 2H), 7.49 - 7.41 (m, 4H), 7.40 - 7.33 (m, 1H), 7.32 - 7.27 (m, 1H), 6.74 – 6.62 (m, 1H), 6.49 -6.43 (m, 1H), 6.34 - 6.20 (m, 1H), 5.81 - 5.68 (m, 1H), 4.53 - 4.15 (m, 1H), 4.13 - 3.89 (m, 1H), 3.89 - 3.74 (m, 2H), 3.65 - 3.44 (m, 1H), 3.06 - 2.92 (m, 3H), 2.25 - 2.15 (m, 1H), 1.97 - 1.87 (m, 2H), 1.75 - 1.65 (m, 1H). [00576] Example 68: 1-(4-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperazin-1-yl)prop-2-en-1-one [00577] Example 68 was prepared in a manner similar to Example 2. MS: m/z = 440.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 8.33 (dd, J = 4.8, 1.6 Hz, 1H), 8.21 (dd, J = 8.0, 1.6 Hz, 1H), 7.99 (dd, J = 4.8, 1.6 Hz, 1H), 7.46 (d, J = 8.4 Hz, 2H), 7.42 - 7.37 (m, 3H), 7.16 (dd, J = 8.0, 2.0 Hz, 1H), 7.01 (br s, 2H), 6.80 (dd, J = 16.8, 10.8 Hz, 1H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 6.11 (dd, J = 16.8, 2.4 Hz, 1H), 5.68 (dd, J = 10.8, 2.4 Hz, 1H), 3.59 - 3.56 (m, 6H), 2.39 (br s, 4H). [00578] Example 69: N-(1-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)acrylamide [00579] Example 69 was prepared in a manner similar to Example 2. MS: m/z = 454.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 8.33 (dd, J = 4.8, 1.2 Hz, 1H), 8.21 (dd, J = 8.0, 1.2 Hz, 1H), 8.05 - 7.97 (m, 2H), 7.45 - 7.36 (m, 5H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.01 (br s, 2H), 6.37 (dd, J = 8.0, 5.2 Hz, 1H), 6.25 - 6.17 (m, 1H), 6.10 - 6.04 (m, 1H), 5.59 - 5.54 (m, 1H), 3.67 - 3.59 (m, 1H), 3.54 (s, 2H), 2.81 - 2.76 (m, 2H), 2.10 - 2.03 (m, 2H), 1.79 - 1.74 (m, 2H), 1.48 - 1.40 (m, 2H). [00580] Example 70: 3-(5-Phenyl-3-(4-((4-(prop-1-en-2-ylsulfonyl)piperazin-1- yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-am ine WSGR Docket No.62619-716.601 [00581] 2Cl2 (20 mL) were added 2Cl ₂ (20 mL). The mixture was stirred at 0 °C for 3 hr. The reaction mixture was quenched with saturated NaHCO3 (10 mL), diluted with H2O (10 mL), and extracted with CH2Cl2 (20 mL x 3). The combined organic layers were washed with brine (20 mL), dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. After purification by silica gel flash chromatography (MeOH in CH2Cl2 = 0% to 8%) and then by prep-HPLC (column: Waters xbridge 150 x 25 mm 4HCO ₃ ) - ACN]; gradient: 38% - 68% B over 14 min), 3-(5- phenyl-3-(4-((4-(prop-1-en-2-ylsulfonyl)piperazin-1-yl)methy l)phenyl)-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine (Example 70, 21.8 mg, yield: 11.5%) was obtained as an off- white powder. MS: m/z = 566.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ J = 8.4 Hz, 1H), 8.05 - 8.01 (m, 2H), 7.98 (dd, J = 4.8, 1.6 Hz, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.54 (d, J = 8.4 Hz, 2H), 7.46 - 7.38 (m, 5H), 7.32 (dd, J = 7.6, 1.6 Hz, 1H), 6.49 (dd, J = 7.6, 4.8 Hz, 1H), 5.92 - 5.90 (m, 1H), 5.78 - 5.76 (m, 1H), 3.68 (s, 2H), 3.28 - 3.25 (m, 4H), 2.61 - 2.56 (m, 4H), 2.06 (s, 3H). [00582] Example 71: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)piperidin-4-yl)prop-1-ene-2-sulfonamide [00583] Example 71 was prepared in a manner similar to Example 70. MS: m/z = 580.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ J = 8.4 Hz, 1H), 8.04 - 8.00 (m, 2H), 7.98 (dd, J = 5.2, 2.0 Hz, 1H), 7.93 (d, J = 8.0 Hz, 1H), 7.50 (d, J = 8.0 Hz, 2H), 7.45 - 7.35 (m, 5H), 7.30 (dd, J = 7.6, 1.6 Hz, 1H), 6.46 (dd, J = 8.0, 5.2 Hz, 1H), 5.94 (d, J = 1.2 Hz, 1H), 5.63 (d, J = 1.2 Hz, 1H), 3.62 (s, 2H), 3.11 - 3.04 (m, 1H), 2.95 - 2.85 (m, 2H), 2.22 - 2.14 (m, 2H), 2.08 (s, 3H), 1.95 - 1.85 (m, 2H), 1.66 - 1.55 (m, 2H). WSGR Docket No.62619-716.601 [00584] Example 72: 1-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)piperazin-1-yl)-2-methoxyprop-2-en-1-one [00585] purification by prep-HPLC (column: [water (NH ₄ HCO ₃ ) - ACN]; B%: 36% - 66%, 18 min), 1- (4-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyr idin-3-yl)benzyl)piperazin-1-yl)- 2-methoxyprop-2-en-1-one (Example 72, 37.3 mg, yield: 21%) was obtained as a light-yellow. MS: m/z = 546.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ J = 8.4 Hz, 1H), 8.03 (d, J = 7.2 Hz, 2H), 7.98 (dd, J = 4.8, 1.6 Hz, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.57 - 7.51 (m, 2H), 7.47 - 7.35 (m, 5H), 7.32 (dd, J = 7.6, 1.6 Hz, 1H), 6.48 (dd, J = 7.6, 5.2 Hz, 1H), 4.49 - 4.44 (m, 2H), 3.66 (s, 2H), 3.65 (s, 3H), 3.64 - 3.53 (m, 4H), 2.56 - 2.49 (m, 4H). [00586] Example 73: (E)-1-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5 -b]pyridin- 3-yl)benzyl)piperazin-1-yl)-4-(dimethylamino)but-2-en-1-one [00587] To a solution of Intermediate 2 (100 mg, 201 µmol), (E)-4-(dimethylamino)but-2-enoic acid (38.9 mg, 301 µmol) in DMF (2 mL) were added DIEA (51.9 mg, 401 µmol) and HATU (84 mg, 221 µmol). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was filtered. After purification by prep-HPLC (column: Waters xbridge 150 x 25 mm x 10 µm; mobile phase: [water (NH4HCO3) - ACN]; B%: %, isocratic elution mode), (E)-1-(4-(4-(2-(2- aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyridin-3-yl)be nzyl)piperazin-1-yl)-4- (dimethylamino)but-2-en-1-one (Example 73, 38.7 mg, yield: 32%) was obtained as a light- yellow solid. MS: m/z = 573.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6) J = 8.4 Hz, 1H), 8.04 - 7.97 (m, 4H), 7.50 - 7.45 (m, 6H), 7.42 - 7.38 (m, 1H), 7.15 (dd, J = 7.6, WSGR Docket No.62619-716.601 2.0 Hz, 1H), 7.02 (br s, 2H), 6.62 - 6.56 (m, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 3.61 (s, 2H), 3.59 - 3.54 (m, 4H), 3.03 - 2.99 (m, 2H), 2.43 - 2.38 (m, 4H), 2.13 (s, 6H). [00588] Example 74: (E)-N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5 - b]pyridin-3-yl)benzyl)piperidin-4-yl)but-2-enamide [00589] To a solution of Intermediate 3 (100 mg, 195 µmol) and (E)-but-2-enoyl chloride (40.8 mg, 391 µmol) in CH ₂ Cl ₂ (2 mL) was added pyridine (46.3 mg, 586 µmol) at 0 °C. The mixture was stirred at 0 °C for 1 hr. The reaction mixture was quenched with MeOH (5 mL) at 25°C and concentrated under reduced pressure. After purification by prep-HPLC (column: Waters xbridge 150 x 25 mm x 10 µm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 30% - 60% B over 14 min), (E)-N-(1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5 -b]pyridin-3- yl)benzyl)piperidin-4-yl)but-2-enamide (Example 74, 4 mg, yield: 3.7%) was obtained as a light-yellow solid. MS: m/z = 544.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ 8.27 (d, J = 8.4 Hz, 1H), 8.05 - 7.96 (m, 4H), 7.78 (d, J = 7.6 Hz, 1H), 7.49 - 7.39 (m, 7H), 7.15 (dd, J = 8.0, 2.0 Hz, 1H), 7.02 (br s, 2H), 6.64 - 6.53 (m, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 5.94 - 5.84 (m, 1H), 3.65 - 3.59 (m, 1H), 3.56 (s, 2H), 2.83 - 2.76 (m, 2H), 2.13 - 2.02 (m, 2H), 1.79 - 1.72 (m, 5H), 1.47 - 1.38 (m, 2H). [00590] Example 75: 1-(4-(4-(2-(2-Aminopyridin-3-yl)-5-cyclopropyl-3H-imidazo[4, 5- b]pyridin-3-yl)benzyl)piperazin-1-yl)prop-2-en-1-one [00591] Example 75 was prepared in a manner similar to Example 2. MS: m/z = 480.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Acetonitrile-d4 8.03 - 7.96 (m, 2H), 7.49 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 8.4 Hz, 2H), 7.23 (d, J = 8.4 Hz, 1H), 7.09 (dd, J = 8.0, 1.6 Hz, 1H), 6.71 (dd, J = 16.8, 10.8 Hz, 1H), 6.53 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 6.17 (dd, J = 16.4, 2.0 Hz, 1H), WSGR Docket No.62619-716.601 5.68 (dd, J = 10.4, 2.4 Hz, 1H), 3.64 - 3.57 (m, 6H), 2.50 - 2.45 (m, 4H), 2.24 - 2.21 (m, 1H), 1.00 - 0.95 (m, 2H), 0.90 - 0.82 (m, 2H). [00592] Example 76: 1-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(cyclohex-1-en-1-yl)-3H-i midazo[4,5- b]pyridin-3-yl)benzyl)piperazin-1-yl)prop-2-en-1-one [00593] Example 76 was prepared in a manner similar to Example 2. MS: m/z = 520.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4) J = 8.8 Hz, 1H), 7.96 (d, J = 4.4 Hz, 1H), 7.58 - 7.48 (m, 3H), 7.42 - 7.35 (m, 2H), 7.28 (d, J = 7.6 Hz, 1H), 6.76 (dd, J = 16.8, 10.8 Hz, 1H), 6.69 - 6.63 (m, 1H), 6.51 - 6.42 (m, 1H), 6.21 (d, J = 16.8 Hz, 1H), 5.75 (d, J = 10.8 Hz, 1H), 3.72 - 3.62 (m, 6H), 2.52 - 2.51 (m, 6H), 2.27 - 2.23 (m, 2H), 1.81 - 1.62 (m, 4H). [00594] Example 77: 1-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(3,6-dihydro-2H-pyran-4-y l)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-1-yl)prop-2-en-1 -one [00595] Example 77 was prepared in a manner similar to Example 2. MS: m/z = 522.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4) J = 8.4 Hz, 1H), 7.97 (dd, J = 5.2, 1.6 Hz, 1H), 7.61 (d, J = 8.4 Hz, 1H), 7.51 (d, J = 8.4 Hz, 2H), 7.38 (d, J = 8.4 Hz, 2H), 7.28 (dd, J = 8.0, 2.0 Hz, 1H), 6.76 (dd, J = 16.8, 10.8 Hz, 1H), 6.68 - 6.67 (m, 1H), 6.46 (dd, J = 7.6, 4.8 Hz, 1H), 6.21 (dd, J = 16.8, 2.0 Hz, 1H), 5.75 (dd, J = 10.8, 2.0 Hz, 1H), 4.37 - 4.28 (m, 2H), 3.89 (t, J = 5.2Hz, 2H), 3.74 - 3.58 (m, 6H), 2.67 - 2.58 (m, 2H), 2.56 - 2.45 (m, 4H). [00596] Example 78: 1-(4-(4-(2-(2-Aminopyridin-3-yl)-5-morpholino-3H-imidazo[4,5 - b]pyridin-3-yl)benzyl)piperazin-1-yl)prop-2-en-1-one WSGR Docket No.62619-716.601 [00597] Example 78 was prepared in a manner similar to Example 2. MS: m/z = 525.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4) J = 8.0 Hz, 2H), 7.32 (d, J = 8.4 Hz, 2H), 7.19 (dd, J = 7.6, 2.0 Hz, 1H), 6.87 (d, J = 8.8 Hz, 1H), 6.76 (dd, J = 16.8, 10.8 Hz, 1H), 6.48 - 6.37 (m, 1H), 6.20 (dd, J = 16.8, 1.6 Hz, 1H), 5.74 (dd, J = 10.8, 1.6 Hz, 1H), 3.78 - 3.73 (m, 4H), 3.71 - 3.64 (m, 4H), 3.61 (s, 2H), 3.51 - 3.45 (m, 4H), 2.54 - 2.46 (m, 4H). [00598] Example 79: 3-(3-(4-((4-Acryloylpiperazin-1-yl)methyl)phenyl)-2-(2-amino pyridin-3- yl)-3H-imidazo[4,5-b]pyridin-5-yl)benzonitrile [00599] Example 79 was prepared in a manner similar to Example 2. MS: m/z = 541.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) J = 8.4 Hz, 1H), 8.12 (d, J = 8.4 Hz, 1H), 8.01 (dd, J = 4.8, 1.6 Hz, 1H), 7.89 – 7.84 (m, 1H), 7.69 (dd, J = 8.0, 8.0 Hz, 1H), 7.53 – 7.45 (m, 4H), 7.16 (dd, J = 7.2, 2.0 Hz, 1H), 7.04 (br s, 2H), 6.80 (dd, J = 16.4, 10.0 Hz, 1H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 6.11 (dd, J = 16.8, 2.4 Hz, 1H), 5.67 (dd, J = 10.0, 2.4 Hz, 1H), 3.62 (s, 2H), 3.61 – 3.52 (m, 4H), 2.45 - 2.37 (m, 4H). [00600] Example 80: 4-(3-(4-((4-Acryloylpiperazin-1-yl)methyl)phenyl)-2-(2-amino pyridin-3- yl)-3H-imidazo[4,5-b]pyridin-5-yl)benzonitrile [00601] Example 80 was prepared in a manner similar to Example 2. MS: m/z = 541.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6) J = 8.4 Hz, 1H), 8.23 (d, J = 8.4 Hz, WSGR Docket No.62619-716.601 2H), 8.13 (d, J = 8.4 Hz, 1H), 8.03 – 7.99 (m, 1H), 7.94 (d, J = 8.4 Hz, 2H), 7.57 - 7.42 (m, 4H), 7.17 (d, J = 7.6 Hz, 1H), 7.03 (br s, 2H), 6.81 (dd, J = 16.8, 10.8 Hz, 1H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 6.17 - 6.07 (m, 1H), 5.69 (d, J = 10.8 Hz, 1H), 3.69 - 3.50 (m, 6H), 2.44 – 2.35 (m, 4H). [00602] Example 81: 1-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(3-fluorophenyl)-3H-imida zo[4,5- b]pyridin-3-yl)benzyl)piperazin-1-yl)prop-2-en-1-one [00603] Example 81 was prepared in a manner similar to Example 2. MS: m/z = 534.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) J = 8.4 Hz, 1H), 8.00 - 7.95 (m, 2H), 7.87 – 7.85 (m, 1H), 7.81 – 7.85 (m, 1H), 7.57 (d, J = 8.4 Hz, 2H), 7.48 - 7.42 (m, 3H), 7.33 (dd, J = 7.6, 1.6 Hz, 1H), 7.16 - 7.06 (m, 1H), 6.76 (dd, J = 16.8, 10.8 Hz, 1H), 6.48 (dd, J = 7.6, 4.8 Hz, 1H), 6.21 (dd, J = 16.8, 1.6 Hz, 1H), 5.75 (dd, J = 10.8, 1.6 Hz, 1H), 3.73 – 3.68 (m, 4H), 3.67 (s, 2H), 2.57 - 2.52 (m, 4H). ¹⁹ F NMR (400 MHz, Dimethylsulfoxide-d ₆ [00604] Example 82: 6-(3-(4-((4-Acryloylpiperazin-1-yl)methyl)phenyl)-2-(2-amino pyridin-3- yl)-3H-imidazo[4,5-b]pyridin-5-yl)pyridin-2(1H)-one [00605] Example 82 was prepared in a manner similar to Example 2. MS: m/z = 533.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4) J = 8.4 Hz, 1H), 8.09 (d, J = 8.4 Hz, 1H), 7.99 (dd, J = 4.8, 1.6 Hz, 1H), 7.70 (dd, J = 8.8, 6.8 Hz, 1H), 7.58 (d, J = 8.4 Hz, 2H), 7.45 (d, J = 8.4 Hz, 2H), 7.29 (dd, J = 7.6, 1.6 Hz, 1H), 7.21 (d, J = 7.2 Hz, 1H), 6.77 (dd, J = 16.8, 10.8 Hz, 1H), 6.57 (d, J = 8.8 Hz, 1H), 6.45 (dd, J = 7.6, 4.8 Hz, 1H), 6.21 (dd, J = 16.8, 2.0 Hz, 1H), 5.75 (dd, J = 10.8, 2.0 Hz, 1H), 3.74 – 3.68 (m, 4H), 3.67 (s, 2H), 2.58 - 2.50 (m, 4H). [00606] Example 83: 5-(3-(4-((4-Acryloylpiperazin-1-yl)methyl)phenyl)-2-(2-amino pyridin-3- yl)-3H-imidazo[4,5-b]pyridin-5-yl)pyridin-2(1H)-one WSGR Docket No.62619-716.601 [00607] Example 83 was prepared in a manner similar to Example 2. MS: m/z = 533.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) J = 9.6, 2.8 Hz, 1H), 8.21 - 8.13 (m, 2H), 7.98 (dd, J = 4.8, 1.6 Hz, 1H), 7.80 (d, J = 8.4 Hz, 1H), 7.55 (d, J = 8.4 Hz, 2H), 7.43 (d, J = 8.4 Hz, 2H), 7.30 (dd, J = 7.6, 2.0 Hz, 1H), 6.77 (dd, J = 16.8, 10.8 Hz, 1H), 6.62 (d, J = 9.6 Hz, 1H), 6.47 (dd, J = 7.6, 4.8 Hz, 1H), 6.25 - 6.18 (m, 1H), 5.75 (dd, J = 10.8, 2.0 Hz, 1H), 3.76 – 3.67 (m, 4H), 3.67 (s, 2H), 2.56 – 2.52 (m, 4H). [00608] Example 84: 1-(4-(4-(2-(2-Aminopyridin-3-yl)-5-(3-chlorophenyl)-3H-imida zo[4,5- b]pyridin-3-yl)benzyl)piperazin-1-yl)prop-2-en-1-one [00609] Example 84 was prepared in a manner similar to Example 2. MS: m/z = 550.1, 552.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4) J = 8.4 Hz, 1H), 8.04 (s, 1H), 8.00 - 7.94 (m, 3H), 7.57 (d, J = 8.4 Hz, 2H), 7.45 (d, J = 8.4 Hz, 2H), 7.41 - 7.36 (m, 2H), 7.33 (dd, J = 7.6, 1.6 Hz, 1H), 6.76 (dd, J = 16.8, 10.4 Hz, 1H), 6.48 (dd, J = 7.6, 4.8 Hz, 1H), 6.21 (dd, J =16.8, 2.0 Hz, 1H), 5.75 (dd, J = 10.4, 2.0 Hz, 1H), 3.72 - 3.68 (m, 4H), 3.67 (s, 2H), 2.56 - 2.52 (m, 4H). [00610] Example 85: 4-(3-(4-((4-Acryloylpiperazin-1-yl)methyl)phenyl)-2-(2-amino pyridin-3- yl)-3H-imidazo[4,5-b]pyridin-5-yl)-1-methylpyridin-2(1H)-one WSGR Docket No.62619-716.601 [00611] Example 85 was prepared in a manner similar to Example 2. MS: m/z = 569.1 [M +Na] ⁺ . 8.19 (d, J = 8.8 Hz, 1H), 8.02 - 7.91 (m, 2H), 7.66 (d, J = 7.2 Hz, 1H), 7.54 (d, J = 8.0 Hz, 2H), 7.41 (d, J = 8.4 Hz, 2H), 7.28 (dd, J = 7.6, 1.6 Hz, 1H), 7.19 (d, J = 1.6 Hz, 1H), 7.05 (dd, J = 7.2, 2.0 Hz, 1H), 6.77 (dd, J = 16.8, 10.4 Hz, 1H), 6.45 (dd, J = 7.6, 5.2 Hz, 1H), 6.21 (dd, J = 16.8, 2.0 Hz, 1H), 5.75 (dd, J = 10.4, 2.0 Hz, 1H), 3.73 - 3.67 (m, 4H), 3.66 (s, 2H), 3.57 (s, 3H), 2.56 - 2.48 (m, 4H). [00612] Example 86: 5-(3-(4-((4-Acryloylpiperazin-1-yl)methyl)phenyl)-2-(2-amino pyridin-3- yl)-3H-imidazo[4,5-b]pyridin-5-yl)-1-methylpyridin-2(1H)-one [00613] Example 86 was prepared in a manner similar to Example 2. MS: m/z = 569.3 [M + Na] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ J = 2.4 Hz, 1H), 8.24 (dd, J = 9.6, 2.8 Hz, 1H), 8.16 (d, J = 8.4 Hz, 1H), 7.98 (dd, J = 5.2, 2.0 Hz, 1H), 7.80 (d, J = 8.4 Hz, 1H), 7.55 (d, J = 8.4 Hz, 2H), 7.43 (d, J = 8.0 Hz, 2H), 7.28 (dd, J = 7.6, 1.6 Hz, 1H), 6.77 (dd, J = 16.8, 10.4 Hz, 1H), 6.61 (d, J = 9.6 Hz, 1H), 6.46 (dd, J = 7.6, 4.8 Hz, 1H), 6.21 (dd, J = 16.8, 2.0 Hz, 1H), 5.75 (dd, J = 10.8, 2.0 Hz, 1H), 3.73 - 3.62 (m, 9H), 2.59 - 2.45 (m, 4H). [00614] Example 87: 3-(3-(4-((4-Acryloylpiperazin-1-yl)methyl)phenyl)-2-(2-amino pyridin-3- yl)-3H-imidazo[4,5-b]pyridin-5-yl)pyridin-2(1H)-one [00615] Example 87 was prepared in a manner similar to Example 2. MS: m/z = 533.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4) J = 8.4 Hz, 1H), 8.35 (dd, J = 7.2, 2.0 Hz, 1H), 8.15 (d, J = 8.8 Hz, 1H), 7.98 (dd, J = 5.2, 2.0 Hz, 1H), 7.55 (d, J = 8.4 Hz, 2H), 7.51 - 7.48 (m, 1H), 7.44 (d, J = 8.8 Hz, 2H), 7.32 (dd, J = 7.6, 1.6 Hz, 1H), 6.77 (dd, J = 16.8, 10.8 Hz, 1H), 6.55 - 6.49 (m, 1H), 6.47 (dd, J = 7.6, 4.8 Hz, 1H), 6.21 (dd, J = 16.8, 2.0 Hz, 1H), 5.75 (dd, J = 10.8, 2.0 Hz, 1H), 3.72 - 3.67 (m, 4H), 3.66 (s, 2H), 2.56 - 2.51 (m, 4H). WSGR Docket No.62619-716.601 [00616] Example 88: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-cyclopropyl-3H-imidazo[4, 5- b]pyridin-3-yl)benzyl)piperidin-4-yl)acrylamide [00617] Example 88 was prepared in a manner similar to Example 2. MS: m/z = 494.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 8.05 - 8.00 (m, 2H), 7.96 (dd, J = 4.8, 1.6 Hz, 1H), 7.42 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 8.4 Hz, 2H), 7.24 (d, J = 8.4 Hz, 1H), 7.06 (dd, J = 7.6, 1.6 Hz, 1H), 6.96 (br s, 2H), 6.33 (dd, J = 8.0, 4.8 Hz, 1H), 6.25 - 6.17 (m, 1H), 6.10 - 6.03 (m, 1H), 5.56 (dd, J = 10.0, 2.4 Hz, 1H), 3.66 - 3.59 (m, 1H), 3.54 (s, 2H), 2.81 - 2.76 (m, 2H), 2.19 - 2.14 (m, 1H), 2.10 - 2.04 (m, 2H), 1.80 - 1.74 (m, 2H), 1.49 - 1.40 (m, 2H), 0.95 - 0.90 (m, 2H), 0.84 - 0.80 (m, 2H). [00618] Example 89: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-(3,6-dihydro-2H-pyran-4-y l)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)acrylamide [00619] Example 89 was prepared in a manner similar to Example 2. MS: m/z = 536.3 [M + H] ⁺ , ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ J = 8.4 Hz, 1H), 8.05 - 7.94 (m, 2H), 7.58 (d, J = 8.4 Hz, 1H), 7.46 - 7.41 (m, 2H), 7.40 - 7.35 (m, 2H), 7.11 (dd, J = 7.6, 2.0 Hz, 1H), 7.01 (br s, 2H), 6.68 (br s, 1H), 6.35 (dd, J = 7.6, 4.8 Hz, 1H), 6.27 - 6.14 (m, 1H), 6.13 - 6.00 (m, 1H), 5.63 - 5.48 (m, 1H), 4.28 - 4.22 (m, 2H), 3.79 (t, J = 5.2 Hz, 2H), 3.65 - 3.60 (m, 1H), 3.55 (s, 2H), 2.79 (d, J = 11.6 Hz, 2H), 2.54 - 2.51 (m, 2H), 2.07 (t, J = 10.8 Hz, 2H), 1.79 - 1.71 (m, 2H), 1.49 - 1.40 (m, 2H). [00620] Example 90: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-(3-fluorophenyl)-3H-imida zo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)acrylamide WSGR Docket No.62619-716.601 [00621] 2Cl2 (10 ml) were added TEA for 2 hr. The resulting mixture was extracted with CH ₂ Cl ₂ (20 mL x 3). The combined organic layers were washed with brine (30 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The crude was purified by silica gel flash chromatography (MeOH in CH2Cl2 = 0% to 10%), N-(1-(4-(2-(2-aminopyridin-3-yl)-5-(3-fluorophenyl)-3H-imida zo[4,5-b]pyridin- 3-yl)benzyl)piperidin-4-yl)acrylamide (Example 90, 8.5 mg, yield: 8%) was obtained as a yellow solid. MS: m/z = 548.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ J = 8.4 Hz, 1H), 8.02 - 7.93 (m, 2H), 7.86 (d, J = 8.0 Hz, 1H), 7.80 - 7.60 (m, 1H), 7.55 (d, J = 8.4 Hz, 2H), 7.48 - 7.41 (m, 3H), 7.32 (dd, J = 7.6, 1.6 Hz, 1H), 7.14 - 7.06 (m, 1H), 6.47 (dd, J = 7.6, 5.2 Hz, 1H), 6.26 - 6.19 (m, 2H), 5.64 (dd, J = 7.6, 4.0 Hz, 1H), 3.84 - 3.72 (m, 1H), 3.65 (s, 2H), 3.03 - 2.85 (m, 2H), 2.28 - 2.13 (m, 2H), 1.95 - 1.84 (m, 2H), 1.65 - 1.53 (m, 2H). [00622] Example 91: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-(3-chlorophenyl)-3H-imida zo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)acrylamide [00623] CH ₂ Cl ₂ 0 °C for 2 hr. The reaction mixture was filtered. After purification by prep-HPLC (column: 4HCO3) - ACN]; gradient: 34% - 64% B over 18 min), N-(1-(4-(2-(2-aminopyridin-3-yl)-5-(3-chlorophenyl)-3H-imida zo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)acrylamide (Example 91, 8.4 mg, yield: 8%) was obtained as a white solid. MS: m/z = 564.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4 J = 8.4 Hz, 1H), 8.06 - 8.04 (m, 1H), 8.00 - 7.94 (m, 3H), 7.56 (d, J = 8.4 Hz, 2H), 7.47 - 7.32 (m, 5H), WSGR Docket No.62619-716.601 6.48 (dd, J = 7.6, 5.2Hz, 1H), 6.27 - 6.20 (m, 2H), 5.64 (dd, J =7.6, 4.0 Hz, 1H), 3.82 - 3.74 (m, 1H), 3.65 (s, 2H), 3.01 - 2.93 (m, 2H), 2.27 - 2.19 (m, 2H), 1.95 - 1.88 (m, 2H), 1.64 - 1.55 (m, 2H). [00624] Example 92: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-(1-methyl-2-oxo-1,2-dihyd ropyridin- 4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)ac rylamide [00625] Example 92 was prepared in a manner similar to Example 2. MS: m/z = 561.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methhanol-d ₄ J = 8.4 Hz, 1H), 8.03 - 7.96 (m, 2H), 7.68 (d, J = 6.8 Hz, 1H), 7.55 (d, J = 8.4 Hz, 2.0H), 7.44 (d, J = 8.4 Hz, 2H), 7.32 (dd, J =7.6, 1.6 Hz, 1H), 7.22 (d, J = 2.0 Hz, 1H), 7.08 (dd, J = 7.2, 2.0 Hz, 1H), 6.46 (dd, J =7.6, 4.8Hz, 1H), 6.28 - 6.17 (m, 2H), 5.64 (dd, J = 7.6, 4.0 Hz, 1H), 3.82 - 3.75 (m, 1H), 3.68 (s, 2H), 3.59 (s, 3H), 3.03 - 2.92 (m, 2H), 2.32 - 2.20 (m, 2H), 1.98 - 1.87 (m, 2H), 1.69 - 1.54 (m, 2H). [00626] Example 93: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-(6-oxo-1,6-dihydropyridin -3-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)acrylamide [00627] Example 93 was prepared in a manner similar to Example 2. MS: m/z = 547.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ 8.31 (dd, J = 9.6, 2.4 Hz, 1H), 8.18 - 8.13 (m, 2H), 7.98 - 7.95 (m, 1H), 7.79 (d, J = 8.4 Hz, 1H), 7.52 (d, J = 8.4 Hz, 2H), 7.42 (d, J = 8.4 Hz, 2H), 7.29 (dd, J = 7.6, 1.6 Hz, 1H), 6.60 (d, J = 9.6 Hz, 1H), 6.46 (dd, J = 7.6, 5.2 Hz, 1H), 6.25 - 6.19 (m, 2H), 5.63 (dd, J = 7.6, 4.4 Hz, 1H), 3.82 - 3.71 (m, 1H), 3.63 (s, 2H), 2.97 - 2.91 (m, 2H), 2.25 - 2.17 (m, 2H), 1.94 - 1.88 (m, 2H), 1.64 - 1.54 (m, 2H). [00628] Example 94: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-(6-oxo-1,6-dihydropyridin -2-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)acrylamide WSGR Docket No.62619-716.601 [00629] Example 94 was prepared in a manner similar to Example 2. MS: m/z = 547.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 10.79 (br s, 1H), 8.34 (d, J = 8.4 Hz, 1H), 8.21 - 8.13 (m, 1H), 8.03 - 7.99 (m, 2H), 7.63 – 7.57 (m, 1H), 7.54 - 7.45 (m, 5H), 7.16 (dd, J = 4.4, 1.6 Hz, 1H), 7.03 (br s, 2H), 6.50 - 6.43 (m, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 6.25 - 6.18 (m, 1H), 6.11 - 6.04 (m, 1H), 5.56 (dd, J = 10.0, 2.0 Hz, 1H), 3.67 - 3.61 (m, 1H), 3.57 (s, 2H), 2.83 - 2.79 (m, 2H), 2.21 – 2.16 (m, 2H), 1.81 - 1.75 (m, 2H), 1.50 - 1.42 (m, 2H). [00630] Example 95: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-(2-oxo-1,2-dihydropyridin -3-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)acrylamide [00631] Example 95 was prepared in a manner similar to Example 2. MS: m/z = 547.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ 12.01 (br s, 1H), 8.68 (d, J = 8.4 Hz, 1H), 8.23 (dd, J = 7.2, 1.6 Hz, 1H), 8.18 (d, J = 8.4 Hz, 1H), 8.04 - 7.98 (m, 2H), 7.50 - 7.41 (m, 5H), 7.13 (d, J = 7.6 Hz, 1H), 7.04 (br s, 2H), 6.39 - 6.34 (m, 2H), 6.26 - 6.17 (m, 1H), 6.10 - 6.04 (m, 1H), 5.56 (dd, J = 10.0, 1.6 Hz, 1H), 3.67 - 3.59 (m, 1H), 3.56 (s, 2H), 2.83 - 2.77 (m, 2H), 2.11 - 2.04 (mz, 2H), 1.80 - 1.74 (m, 2H), 1.49 - 1.39 (m, 2H). [00632] Example 96: N-(1-(4-(2-(2-Aminopyridin-3-yl)-6-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)piperidin-4-yl)acrylamide WSGR Docket No.62619-716.601 [00633] Example 96 was prepared in a manner similar to Example 2. MS: m/z = 530.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) 8.64 (d, J = 2.0 Hz, 1H), 8.47 (d, J = 2.0 Hz, 1H), 8.03 - 7.99 (m, 2H), 7.79 (d, J = 7.6 Hz, 2H), 7.53 (dd, J = 7.6, 7.6 Hz, 2H), 7.48 - 7.39 (m, 5H), 7.20 (dd, J = 7.6, 1.6 Hz, 1H), 7.06 (br s, 2H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 6.26 - 6.18 (m, 1H), 6.10 - 6.04 (m, 1H), 5.56 (dd, J = 10.0, 2.4 Hz, 1H), 3.68 - 3.59 (m, 1H), 3.55 (s, 2H), 2.80 (d, J = 11.6 Hz, 2H), 2.07 (t, J = 11.6 Hz, 2H), 1.84 - 1.70 (m, 2H), 1.51 - 1.38 (m, 2H). [00634] Example 97: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)piperidin-4-yl)-N-methylacrylamide [00635] To a solution of Intermediate 69 (80 mg, 164 µmol) in THF (10 mL) were added TEA (49.6 mg, 490 µmol) and acryloyl chloride (17.8 mg, 196 µmol) at 0 °C. The reaction mixture was stirred at 0 °C for 1 hr. The mixture was quenched with MeOH (1 mL) and concentrated under reduced pressure. After purification by prep-HPLC (column: Waters xbridge 150 x 25 mm 10 µm; mobile phase: [water (NH4HCO3) - ACN]; B%: 30% - 60%, 14 min), N-(1-(4-(2-(2- aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyridin-3-yl)be nzyl)piperidin-4-yl)-N- methylacrylamide (Example 97, 15.3 mg, yield: 17%) was obtained as a yellow solid. MS: m/z = 544.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4) J = 8.4 Hz, 1H), 8.03 (d, J = 7.6 Hz, 2H), 7.98 - 7.94 (m, 1H), 7.93 (d, J = 8.4 Hz, 1H), 7.56 - 7.50 (m, 2H), 7.47 - 7.30 (m, 6H), 6.85 - 6.63 (m, 1H), 6.47 (dd, J = 7.2, 4.8 Hz, 1H), 6.23 - 6.11 (m, 1H), 5.75 - 5.68 (m, 1H), 3.98 - 3.78 (m, 1H), 3.64 (s, 3H), 3.05 (d, J = 12.0 Hz, 2H), 2.99 - 2.98 (m, 1H), 2.91 - 2.87 (m, 1H), 2.24 - 2.16 (m, 2H), 2.03 - 1.85 (m, 2H), 1.69 - 1.59 (m, 2H). [00636] Example 98: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)piperidin-4-yl)-N-(methyl-d3)acrylamide WSGR Docket No.62619-716.601 [00637] Following the general procedure of Example 97, the reaction of Intermediate 70 (50 mg, 102 µmol) with acryloyl chloride (11 mg, 122 µmol) was carried out. After purification by prep- TLC (MeOH in CH ₂ Cl ₂ = 10%), N-(1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)-N-(methyl-d3)acrylamid e (Example 98, 8 mg, yield: 15%) was obtained as a yellow solid. MS: m/z = 547.6 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) 8.18 (d, J = 8.4 Hz, 1H), 8.02 (d, J = 7.2 Hz, 2H), 7.97 (dd, J = 5.2, 1.6 Hz, 1H), 7.93 (d, J = 8.0 Hz, 1H), 7.53 (d, J = 8.0 Hz, 2H), 7.48 - 7.28 (m, 6H), 6.87 - 6.67 (m, 1H), 6.46 (dd, J = 7.2, 5.2 Hz, 1H), 6.29 - 6.07 (m, 1H), 5.85 - 5.62 (m, 1H), 4.50 - 4.39 (m, 0.5H), 4.05 - 3.77 (m, 0.5H), 3.64 (s, 2H), 3.04 (d, J = 11.2 Hz, 2H), 2.26 - 2.14 (m, 2H), 2.02 - 1.81 (m, 2H), 1.71 - 1.59 (m, 2H). [00638] Example 99: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-(3-cyanophenyl)-3H-imidaz o[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)acrylamide [00639] Example 99 was prepared in a manner similar to Example 2. MS: m/z = 555.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6) J = 8.0 Hz, 1H), 8.32 (d, J = 8.4 Hz, 1H), 8.12 (d, J = 8.4 Hz, 1H), 8.04 - 7.97 (m, 2H), 7.86 (d, J = 7.6 Hz, 1H), 7.69 (dd, J = 8.0, 8.0 Hz, 1H), 7.51 - 7.44 (m, 4H), 7.16 (d, J = 6.8 Hz, 1H), 7.03 (br s, 2H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 6.27 - 6.17 (m, 1H), 6.12 - 6.01 (m, 1H), 5.62 - 5.50 (m, 1H), 3.65 - 3.61 (m, 1H), 3.57 (s, 2H), 2.83 - 2.79 (m, 2H), 2.09 (t, J = 12.4 Hz, 2H), 1.81 - 1.73 (m, 2H), 1.50 - 1.39 (m, 2H). [00640] Example 100: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-(cyclohex-1-en-1-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)acrylamide WSGR Docket No.62619-716.601 [00641] Example 100 was prepared in a manner similar to Example 2. MS: m/z = 534.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) J = 8.0 Hz, 1H), 7.95 (dd, J = 4.8, 1.6 Hz, 1H), 7.54 (d, J = 8.8 Hz, 1H), 7.49 (d, J = 8.4 Hz, 2H), 7.38 (d, J = 8.0 Hz, 2H), 7.28 (dd, J = 7.6, 1.6 Hz, 1H), 6.74 - 6.58 (m, 1H), 6.45 (dd, J = 8.0, 5.2 Hz, 1H), 6.31 - 6.08 (m, 2H), 5.63 (dd, J = 7.6, 4.4 Hz, 1H), 3.78 - 3.72 (m, 1H), 3.61 (s, 2H), 2.96 - 2.90 (m, 2H), 2.50 - 2.48(m, 2H), 2.26 - 2.16 (m, 4H), 1.92 - 1.86 (m, 2H), 1.78 - 1.72 (m, 2H), 1.70 - 1.63 (m, 2H), 1.61 - 1.53 (m, 2H). [00642] Example 101: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-cyclohexyl-3H-imidazo[4,5 - b]pyridin-3-yl)benzyl)piperidin-4-yl)acrylamide [00643] Example 101 was prepared in a manner similar to Example 2. MS: m/z = 536.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 J = 8.4 Hz, 1H), 8.00 (d, J = 7.6 Hz, 1H), 7.98 - 7.94 (m, 1H), 7.43 (d, J = 8.4 Hz, 2H), 7.38 - 7.31 (m, 2H), 7.27 (d, J = 8.4 Hz, 1H), 7.07 (dd, J = 7.6, 1.6 Hz, 1H), 6.91 (br s, 2H), 6.33 (dd, J = 7.6, 4.8 Hz, 1H), 6.26 - 6.16 (m, 1H), 6.11 - 6.05 (m, 1H), 5.60 - 5.52 (m, 1H), 3.67 - 3.58 (m, 1H), 3.54 (s, 2H), 2.83 - 2.75 (m, 2H), 2.74 - 2.68 (m, 1H), 2.11 - 2.03 (m, 2H), 1.86 - 1.81 (m, 2H), 1.77 (d, J = 11.2 Hz, 4H), 1.71 - 1.64 (m, 1H), 1.50 - 1.42 (m, 4H), 1.40 - 1.30 (m, 2H), 1.26 - 1.19 (m, 1H). [00644] Example 102: N-(1-(4-(2-(2-Aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)-N-methylacrylamide [00645] To a solution of Intermediate 75 (200 mg, 537 µmol) and Intermediate 74 (152 mg, 537 µmol) in DMF (3 mL) were added NaI (40.3 mg, 269 µmol) and K ₂ CO ₃ (371 mg, 2.69 mmol). The mixture was stirred at 50 °C for 2 hr. The reaction mixture was filtered. After purification by prep-HPLC (column: Phenomenex C18 150 x 25 mm x 10 µm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 19% - 49% B over 10 min), N-(1-(4-(2-(2-aminopyridin-3-yl)-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)-N-methylac rylamide (Example 102, 55.1 mg, WSGR Docket No.62619-716.601 yield: 21%) was obtained as a light-yellow solid. MS: m/z = 468.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ ) J = 4.0 Hz, 1H), 8.21 (d, J = 8.0 Hz, 1H), 8.01 - 7.95 (m, 1H), 7.50 - 7.34 (m, 6H), 7.19 - 7.14 (m, 1H), 7.02 (s, 1H), 6.83 - 6.69 (m, 1H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 6.12 - 6.02 (m, 1H), 5.69 - 5.60 (m, 1H), 4.37 - 4.27 (m,0.6H), 3.84 - 3.74(m, 0.4H), 3.55 (s, 2H), 2.90 (s, 3H), 2.77 (s, 2H), 2.11 - 2.01 (m, 2H), 1.84 - 1.69 (m, 2H), 1.58 - 1.46 (m, 2H). [00646] Example 103: (S)-N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5 - b]pyridin-3-yl)benzyl)piperidin-3-yl)ethenesulfonamide [00647] Example 103 was prepared in a manner similar to Example 4. MS: m/z = 566.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4 8.17 (d, J = 8.4 Hz, 1H), 8.05 - 8.00 (m, 2H), 7.97 (dd, J = 5.2, 2.0 Hz, 1H), 7.92 (d, J = 8.4 Hz, 1H), 7.53 - 7.48 (m, 2H), 7.45 - 7.39 (m, 4H), 7.38 - 7.34 (m, 1H), 7.28 (dd, J = 7.6, 1.6 Hz, 1H), 6.58 (dd, J = 16.8, 10.0 Hz, 1H), 6.50 (dd, J = 7.6, 5.2 Hz, 1H), 6.06 (d, J = 16.4 Hz, 1H), 5.82 (d, J = 10.0 Hz, 1H), 3.68 - 3.52 (m, 2H), 3.29 - 3.25 (m, 1H), 2.97 - 2.87 (m, 1H), 2.79 - 2.69 (m, 1H), 2.19 - 2.09 (m, 1H), 2.05 - 1.95 (m, 1H), 1.92 - 1.84 (m, 1H), 1.80 - 1.72 (m, 1H), 1.68 - 1.52 (m, 2H). [00648] Example 104: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)azetidin-3-yl)ethenesulfonamide [00649] Example 104 was prepared in a manner similar to Example 4. MS: m/z = 538.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ 8.19 (d, J = 8.4 Hz, 1H), 8.03 (d, J = 7.2 Hz, 2H), 7.98 (dd, J = 4.8, 1.6 Hz, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.50 - 7.36 (m, 7H), 7.31 (dd, J = 7.2, 1.6 Hz, 1H), 6.65 (dd, J = 16.4, 10.0 Hz, 1H), 6.48 (dd, J = 7.6, 5.2 Hz, 1H), 6.16 (d, J = 16.4 Hz, 1H), 5.96 (d, J = 10.0 Hz, 1H), 4.02 - 3.92 (m, 1H), 3.74 (s, 2H), 3.71 - 3.64 (m, 2H), 3.14 - 3.05 (m, 2H). WSGR Docket No.62619-716.601 [00650] Example 105: (S)-N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5 - b]pyridin-3-yl)benzyl)pyrrolidin-3-yl)ethenesulfonamide [00651] Example 104 was prepared in a manner similar to Example 4. MS: m/z = 552.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4 J = 8.4 Hz, 1H), 8.03 (d, J = 7.2 Hz, 2H), 7.98 (dd, J = 4.8, 2.0 Hz, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.54 (d, J = 8.4 Hz, 2H), 7.47 - 7.40 (m, 4H), 7.39 - 7.36 (m, 1H), 7.31 (dd, J = 7.6, 1.6 Hz, 1H), 6.65 (dd, J = 16.4, 10.0 Hz, 1H), 6.49 (dd, J = 7.6, 5.2 Hz, 1H), 6.14 (d, J = 16.4 Hz, 1H), 5.93 (d, J = 10.0 Hz, 1H), 3.87 - 3.81 (m, 1H), 3.80 - 3.70 (m, 2H), 2.93 - 2.86 (m, 1H), 2.79 - 2.71 (m, 1H), 2.68 - 2.61 (m, 1H), 2.59 - 2.53 (m, 1H), 2.31 - 2.23 (m, 1H), 1.81 - 1.73 (m, 1H). [00652] Example 106: 3-(5-Phenyl-3-(4-((2-(vinylsulfonyl)-2,6-diazaspiro[3.4]octa n-6- yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-am ine [00653] To a solution of Intermediate 19 (50 mg, 102 µmol) and TEA (52 mg, 513 µmol) in CH ₂ Cl ₂ (10 mL) was added dropwise a solution of 2-chloroethane-1-sulfonyl chloride (20 mg, 123 µmol) in CH2Cl2 (5 mL) at 0 °C. The reaction mixture was stirred at 0 °C for 0.5 hr. The reaction mixture was quenched with saturated NaHCO ₃ (aq) (10 mL) at 0 °C and extracted with CH ₂ Cl ₂ (20 mL x 2). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purification by silica gel flash chromatography (MeOH in CH ₂ Cl ₂ = 0% to 8%), 3-(5-phenyl-3-(4-((2-(vinylsulfonyl)-2,6- diazaspiro[3.4]octan-6-yl)methyl)phenyl)-3H-imidazo[4,5-b]py ridin-2-yl)pyridin-2-amine (Example 106, 11.2 mg, yield: 18%) was obtained as a yellow solid. MS: m/z = 578.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ J = 8.4 Hz, 1H), 8.03 (d, J = 7.2 Hz, 2H), 7.98 (dd, J = 4.8, 1.6 Hz, 1H), 7.93 (d, J = 8.4 Hz, 1H), 7.51 (d, J = 8.4 Hz, 2H), 7.46 - 7.40 (m, 4H), 7.37 (d, J = 7.0 Hz, 1H), 7.30 (dd, J = 7.6, 1.6 Hz, 1H), 6.78 (dd, J = 16.8, 10.0 Hz, 1H), 6.48 (dd, J = WSGR Docket No.62619-716.601 7.6, 4.8 Hz, 1H), 6.26 - 6.20 (m, 2H), 3.78 (s, 4H), 3.71 (s, 2H), 2.78 (s, 2H), 2.65 (t, J = 7.2 Hz, 2H), 2.09 (t, J = 7.2 Hz, 2H). [00654] Example 107: (S)-3-(5-Phenyl-3-(4-((7-(vinylsulfonyl)-2,7-diazaspiro[4.4] nonan-2- yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-am ine [00655] To a solution of Intermediate 41 (50 mg, 100 µmol) and TEA (50 mg, 498 µmol) in CH2Cl2 (10 mL) was added dropwise a solution of 2-chloroethane-1-sulfonyl chloride (21 mg, 130 µmol) in CH2Cl2 (5 mL) at 0 °C. The reaction mixture was stirred at 0 °C for 0.5 hr. The reaction mixture was quenched with saturated NaHCO3 (aq) (10 mL) at 0 °C and extracted with CH2Cl2 (20 mL x 2). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give a residue. After purification by silica gel flash chromatography (MeOH in CH2Cl2 = 0% to 8%), (S)-3-(5-phenyl-3-(4-((7-(vinylsulfonyl)- 2,7-diazaspiro[4.4]nonan-2-yl)methyl)phenyl)-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine (Example 107, 10.5 mg, yield: 18%) was obtained as a yellow solid. MS: m/z = 592.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4 J = 8.4 Hz, 1H), 8.02 (d, J = 6.8 Hz, 2H), 7.98 (dd, J = 5.2, 1.6 Hz, 1H), 7.92 (d, J = 8.4 Hz, 1H), 7.51 (d, J = 8.4 Hz, 2H), 7.44 - 7.39 (m, 4H), 7.37 (d, J = 7.2 Hz, 1H), 7.28 (dd, J = 7.6, 1.6 Hz, 1H), 6.64 (dd, J = 16.4, 10.0 Hz, 1H), 6.47 (dd, J = 7.6, 5.2 Hz, 1H), 6.12 (d, J = 16.8 Hz, 1H), 6.00 (d, J = 10.0 Hz, 1H), 3.79 - 3.63 (m, 2H), 3.37 - 3.32 (m, 1H), 3.28 - 3.21 (m, 2H), 3.15 (d, J = 10.0 Hz, 1H), 2.81 - 2.73 (m, 1H), 2.68 - 2.59 (m, 2H), 2.44 (d, J = 9.6 Hz, 1H), 1.96 - 1.88 (m, 2H), 1.88 - 1.78 (m, 2H). [00656] Example 108: 3-(5-Phenyl-3-(4-((6-(vinylsulfonyl)-2,6-diazaspiro[3.3]hept an-2- yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-am ine [00657] To a solution of Intermediate 5 (70 mg, 148 µmol) and TEA (75 mg, 739 µmol) in CH2Cl2 (10 mL) was added dropwise a solution of 2-chloroethane-1-sulfonyl chloride (31 mg, 192 WSGR Docket No.62619-716.601 µmol) in CH2Cl2 (5 mL) at 0 °C. The reaction mixture was stirred at 0 °C for 0.5 hr. The reaction mixture was quenched with saturated NaHCO ₃ (aq) (10 mL) at 0 °C and extracted with CH ₂ Cl ₂ (20 mL x 2). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The crude was purified by silica gel flash chromatography (MeOH in CH ₂ Cl ₂ = 0% to 8%), 3-(5-phenyl-3-(4-((6-(vinylsulfonyl)-2,6- diazaspiro[3.3]heptan-2-yl)methyl)phenyl)-3H-imidazo[4,5-b]p yridin-2-yl)pyridin-2-amine (Example 108, 11.3 mg, yield: 13%) was obtained as a yellow solid. MS: m/z = 564.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ J = 8.4 Hz, 1H), 8.00 (d, J = 6.8 Hz, 2H), 7.97 (dd, J = 4.8, 1.6 Hz, 1H), 7.90 (d, J = 8.4 Hz, 1H), 7.44 - 7.35 (m, 7H), 7.26 (dd, J = 7.6, 2.0 Hz, 1H), 6.76 (dd, J = 16.4, 10.0 Hz, 1H), 6.44 (dd, J = 7.6, 5.2 Hz, 1H), 6.27 - 6.19 (m, 2H), 3.94 (s, 4H), 3.65 (s, 2H), 3.40 (s, 4H). [00658] Example 109: 3-(5-Phenyl-3-(4-(((1R,4R)-5-(vinylsulfonyl)-2,5- diazabicyclo[2.2.1]heptan-2-yl)methyl)phenyl)-3H-imidazo[4,5 -b]pyridin-2-yl)pyridin-2-amine [00659] To a solution of Intermediate 36 (70 mg, 148 µmol) and TEA (75 mg, 739 µmol) in CH2Cl2 (10 mL) was added dropwise a solution of 2-chloroethane-1-sulfonyl chloride (31 mg, 192 µmol) in CH ₂ Cl ₂ (5 mL) at 0 °C. The reaction mixture was stirred at 0 °C for 0.5 hr. The reaction mixture was quenched with saturated NaHCO ₃ (aq) (10 mL) at 0 °C and extracted with CH ₂ Cl ₂ (20 mL x 2). The combined organic layers were washed with brine (50 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The crude was purified by silica gel flash chromatography (MeOH in CH ₂ Cl ₂ = 0 – 8%), 3-(5-phenyl-3-(4-(((1R,4R)-5-(vinylsulfonyl)-2,5- diazabicyclo[2.2.1]heptan-2-yl)methyl)phenyl)-3H-imidazo[4,5 -b]pyridin-2-yl)pyridin-2-amine (Example 109, 18 mg, yield: 21%) was obtained as a yellow solid. MS: m/z = 564.1[M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4 J = 8.4 Hz, 1H), 8.03 (d, J = 6.8 Hz, 2H), 7.98 (dd, J = 5.2, 2.0 Hz, 1H), 7.94 (d, J = 8.8 Hz, 1H), 7.56 (d, J = 8.4 Hz, 2H), 7.46 - 7.40 (m, 4H), 7.39 - 7.36 (m, 1H), 7.32 (dd, J = 7.6, 2.0 Hz, 1H), 6.74 (dd, J = 16.4, 10.0 Hz, 1H), 6.48 (dd, J = 7.6, 4.8 Hz, 1H), 6.20 (d, J = 16.4 Hz, 1H), 6.07 (d, J = 10.0 Hz, 1H), 4.24 (m, 1H), 3.95 - 3.83 (m, 2H), 3.64 (m, 1H), 3.57 (d, J = 10.0 Hz, 1H), 3.15 (dd, J = 9.6, 2.4 Hz, 1H), 2.94 - 2.83 (m, 2H), 1.99 - 1.93 (m, 1H), 1.72 (d, J = 10.4 Hz, 1H). WSGR Docket No.62619-716.601 [00660] Example 110: 3-(5-Phenyl-3-(4-((5-(vinylsulfonyl)-2,5-diazabicyclo[2.2.2] octan-2- yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-am ine [00661] Example 110 was prepared in a manner similar to Example 4. MS: m/z = 578.1 [M + H] ⁺ . 1H NMR (400 MHz, Methanol-d ₄ J = 8.4 Hz, 1H), 8.05 - 8.00 (m, 2H), 7.98 (dd, J = 4.8, 2.0 Hz, 1H), 7.93 (d, J = 8.4 Hz, 1H), 7.54 (d, J = 8.4 Hz, 2H), 7.45 - 7.39 (m, 4H), 7.39 - 7.35 (m, 1H), 7.30 (dd, J = 7.6, 2.0 Hz, 1H), 6.72 (dd, J = 16.4, 10.0 Hz, 1H), 6.47 (dd, J = 7.6, 5.2 Hz, 1H), 6.18 (d, J = 16.4 Hz, 1H), 6.03 (d, J = 10.0 Hz, 1H), 3.85 (s, 2H), 3.79 - 3.75 (m, 1H), 3.72 - 3.67 (m, 1H), 3.26 (dd, J = 9.6, 2.0 Hz, 1H), 3.06 - 3.01 (m, 1H), 2.98 - 2.94 (m, 1H), 2.88 (dd, J = 10.8, 2.0 Hz, 1H), 2.20 - 2.08 (m, 1H), 2.04 - 1.96 (m, 1H), 1.88 - 1.81 (m, 1H), 1.76 - 1.65 (m, 1H). [00662] Example 111: N-(7-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)-7-azaspiro[3.5]nonan-2-yl)ethenesulfonamide [00663] To a solution of Intermediate 13 (100 mg, 181 µmol) and TEA (55 mg, 543 µmol) in CH ₂ Cl ₂ (12 mL) was added 2-chloroethane-1-sulfonyl chloride (38 mg, 235 µmol) in CH ₂ Cl ₂ (1 mL) at 0 °C. The resulting mixture was stirred at 0 °C for 16 hr. The reaction mixture was quenched with saturated NaHCO ₃ (10 mL) at 0 °C and extracted with CH ₂ Cl ₂ (20 mL x 2). The combined organic layers were washed with brine (50 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. After purification by prep-TLC (MeOH in CH2Cl2 = 10%), N-(7-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3-yl)benzyl)-7- azaspiro[3.5]nonan-2-yl)ethenesulfonamide (Example 111, 9 mg, yield: 7.9%) was obtained as a light-yellow solid. MS: m/z = 606.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 (d, J = 8.4 Hz, 1H), 8.04 - 7.97 (m, 4H), 7.59 (d, J = 8.4 Hz, 1H), 7.48 - 7.39 (m, 7H), 7.15 (dd, J = 7.6, 1.2 Hz, 1H), 7.03 (br s, 2H), 6.68 (dd, J = 16.4, 10.0 Hz, 1H), 6.36 (dd, J = 8.0, 4.8 Hz, WSGR Docket No.62619-716.601 1H), 6.01 (d, J = 16.4 Hz, 1H), 5.92 (d, J = 10.0 Hz, 1H), 3.69 - 3.59 (m, 1H), 3.51 (s, 2H), 2.35 - 2.30 (m, 2H), 2.28 - 2.22 (m, 2H), 2.15 - 2.09 (m, 2H), 1.70 - 1.64 (m, 2H), 1.54 - 1.48 (m, 4H). [00664] Example 112: 3-(5-Phenyl-3-(4-((4-(vinylsulfonyl)-1,4-diazepan-1-yl)methy l)phenyl)- 3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00665] Example 112 was prepared in a manner similar to Example 4. MS: m/z = 566.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ J = 8.4 Hz, 1H), 8.06 - 8.02 (m, 2H), 7.98 (dd, J = 4.8, 1.6 Hz, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.55 (d, J = 8.0 Hz, 2H), 7.47 - 7.35 (m, 5H), 7.33 - 7.29 (m, 1H), 6.66 (dd, J = 16.4, 10.0 Hz, 1H), 6.48 (dd, J = 7.6, 5.2 Hz, 1H), 6.12 (d, J = 16.4 Hz, 1H), 5.99 (d, J = 10.0 Hz, 1H), 3.80 (s, 2H), 3.43 - 3.39 (m, 4H), 2.81 - 2.77 (m, 4H), 1.98 - 1.84 (m, 2H). [00666] Example 113 & 114: N-((5r,8r)-2-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-2-azaspiro[4.5]decan-8-yl )ethenesulfonamide & N-((5s,8s)- 2-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyri din-3-yl)benzyl)-2- azaspiro[4.5]decan-8-yl)ethenesulfonamide [00667] To a solution of Intermediate 8 (50 mg, 94 µmol) and TEA (48 mg, 472 µmol) in CH ₂ Cl ₂ (10 mL) was added dropwise a solution of 2-chloroethane-1-sulfonyl chloride (15 mg, 94.4 µmol) in CH ₂ Cl ₂ (5 mL) at 0 °C. The reaction mixture was stirred at 0 °C for 1 hr. The reaction mixture was quenched with NaHCO ₃ (aq) (10 mL) at 0 °C and extracted with CH ₂ Cl ₂ (20 mL x 2). The combined organic layers were washed with brine (50 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. After purification by silica gel flash chromatography (MeOH in CH ₂ Cl ₂ = 0% to 7%), N-((5r,8r)-2-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-2-azaspiro[4.5]decan-8-yl )ethenesulfonamide (Example 113, 4.0 mg, yield: 6.9%) and N-((5s,8s)-2-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo [4,5- WSGR Docket No.62619-716.601 b]pyridin-3-yl)benzyl)-2-azaspiro[4.5]decan-8-yl)ethenesulfo namide (Example 114, 4.0 mg, yield: 6.9%) were obtained as yellow solid. Spectra for Example 113: MS: m/z = 620.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ J = 8.4 Hz, 1H), 8.05 - 8.01 (m, 2H), 7.99 (dd, J = 5.2, 2.0 Hz, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.57 - 7.51 (m, 2H), 7.46 - 7.40 (m, 4H), 7.40 - 7.36 (m, 1H), 7.34 (dd, J = 7.6, 2.0 Hz, 1H), 6.64 (dd, J = 16.4, 10.0 Hz, 1H), 6.49 (dd, J = 8.0, 5.2 Hz, 1H), 6.12 (d, J = 16.4 Hz, 1H), 5.90 (d, J = 10.0 Hz, 1H), 3.73 (s, 2H), 3.11 - 3.00 (m, 1H), 2.71 - 2.64 (m, 2H), 2.50 (s, 2H), 1.88 - 1.81 (m, 2H), 1.76 - 1.69 (m, 2H), 1.66 - 1.59 (m, 2H), 1.44 - 1.33 (m, 4H). Spectra for Example 114: MS: m/z = 620.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4 J = 8.4 Hz, 1H), 8.06 - 8.00 (m, 2H), 7.98 (dd, J = 5.2, 2.0 Hz, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.58 - 7.51 (m, 2H), 7.48 - 7.40 (m, 4H), 7.40 - 7.36 (m, 1H), 7.33 (dd, J = 8.0, 2.0 Hz, 1H), 6.66 (dd, J = 16.4, 10.0 Hz, 1H), 6.47 (dd, J = 7.6, 5.2 Hz, 1H), 6.12 (d, J = 16.4 Hz, 1H), 5.90 (d, J = 10.0 Hz, 1H), 3.78 (s, 2H), 3.10 - 3.02 (m, 1H), 2.83 - 2.74 (m, 2H), 2.53 - 2.47 (m, 2H), 1.87 - 1.81 (m, 2H), 1.75 - 1.68 (m, 4H), 1.44 - 1.39 (m, 4H). Structures of Example 113 and 114 were tentatively assigned. [00668] Example 115: 3-(5-Phenyl-3-(4-((2-(prop-1-en-2-ylsulfonyl)-2,7-diazaspiro [3.5]nonan- 7-yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2- amine [00669] 2Cl2 (40 mL) was added DIEA CH ₂ Cl ₂ (5 mL) was added at 0 °C. The mixture was stirred at 0 °C for 5 hr. The reaction mixture was diluted with H2O (20 mL) and extracted with CH2Cl2 (20 mL x 3). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. After purification by silica gel flash chromatography (MeOH in CH ₂ Cl ₂ = 0% to 5%), the residue was purified prep-TLC (CH2Cl2 in MeOH = 10:1) and by prep-HPLC (column: Waters xbridge 150 * 4HCO3) - ACN]; gradient: 48% - 78% B over 10 min), 3-(5-phenyl-3-(4-((2-(prop-1-en-2-ylsulfonyl)-2,7-diazaspiro [3.5]nonan-7-yl)methyl)phenyl)- 3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (Example 115, 7.7 mg, yield: 6.1%) was obtained as a light-yellow powder. MS: m/z = 606.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide- d ₆ J = 8.4 Hz, 1H), 8.04 - 7.97 (m, 4H), 7.48 - 7.38 (m, 7H), 7.14 (dd, J = 7.6, 1.6 Hz, WSGR Docket No.62619-716.601 1H), 7.02 (br s, 2H), 6.37 (dd, J = 8.0, 4.8 Hz, 1H), 5.92 - 5.84 (m, 2H), 3.55 (s, 4H), 3.53 (s, 2H), 2.38 - 2.25 (m, 4H), 2.06 (s, 3H), 1.75 - 1.65 (m, 4H). [00670] Example 116: 1-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)piperazin-1-yl)-2-fluoroprop-2-en-1-one [00671] To a solution of Intermediate 2 (150 mg, 260 mmol) and TEA (52.6 mg, 519 mmol) in DMF (3 mL) were added 2-fluoroacrylic acid (30.4 mg, 338 mmol), EDCI (74.8 mg, 389 mmol) and DMAP (3.18 mg, 26.0 mmol). The mixture was stirred at 25 °C for 4 hr. The reaction mixture was filtered. After purification by prep-HPLC (column: [water (NH ₄ HCO ₃ ) - ACN]; B%: 39% - 69%, 18 min), 1-(4-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)piperazin-1-yl)-2-fluoroprop-2-en-1-one (Example 116, 7.7 mg, yield: 5%) was obtained as a yellow solid. MS: m/z = 534.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4 8.19 (d, J = 8.4 Hz, 1H), 8.03 (dd, J = 8.8, 1.6 Hz, 2H), 7.98 (dd, J = 4.8, 1.6 Hz, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.57 - 7.53 (m, 2H), 7.47 - 7.37 (m, 5H), 7.32 (dd, J = 7.6, 2.0 Hz, 1H), 6.51 - 6.45 (m, 1H), 5.24 (s, 1H), 5.20 - 5.12 (m, 1H), 3.70 - 3.65 (m, 6H), 2.59 - 2.52 (m, 4H). ¹⁹ F NMR (400 MHz, Methanol-d ₄ [00672] Example 117: 3-(5-Phenyl-3-(4-((2-(vinylsulfonyl)-2,9-diazaspiro[5.5]unde can-9- yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-am ine [00673] To a solution of Intermediate 25 (50 mg, 94.4 µmol) and TEA (48 mg, 472 µmol) in CH2Cl2 (2 mL) was added 2-chloroethane-1-sulfonyl chloride (23 mg, 142 µmol) at 0 °C. The reaction mixture was stirred at 25 °C for 1 hr. The reaction mixture was quenched with NaHCO ₃ (aq) (1 mL) at 0 °C and concentrated under reduced pressure. After purification by prep-HPLC (column: Waters xbridge 150 * 25 mm 10 µm; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; B%: 48% - 78%, 8 min), 3-(5-phenyl-3-(4-((2-(vinylsulfonyl)-2,9-diazaspiro[5.5]unde can-9- WSGR Docket No.62619-716.601 yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-am ine (Example 117, 3.1 mg, yield: 5%) was obtained as a light-yellow solid. MS: m/z = 620.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ 8.20 (d, J = 8.4 Hz, 1H), 8.05 - 8.02 (m, 2H), 7.99 (dd, J = 5.2, 2.0 Hz, 1H), 7.95 (d, J = 8.4 Hz, 1H), 7.57 - 7.53 (m, 2H), 7.48 - 7.41 (m, 4H), 7.40 - 7.37 (m, 1H), 7.34 (dd, J = 7.6, 1.6 Hz, 1H), 6.61 (dd, J = 16.8, 10.4 Hz, 1H), 6.49 (dd, J = 7.6, 5.2 Hz, 1H), 6.15 (d, J = 16.8 Hz, 1H), 6.07 (d, J = 10.0 Hz, 1H), 3.72 (s, 2H), 3.12 - 3.06 (m, 2H), 2.98 (s, 2H), 2.70 - 2.63 (m, 2H), 2.54 - 2.44 (m, 2H), 1.73 - 1.66 (m, 4H), 1.61 - 1.55 (m, 2H), 1.48 - 1.43 (m, 2H). [00674] Example 118: (R)-3-(3-(4-((3-Methyl-4-(vinylsulfonyl)piperazin-1-yl)methy l)phenyl)-5- phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00675] Example 118 was prepared in a manner similar to Example 4. MS: m/z = 566.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4 8.20 (d, J = 8.4 Hz, 1H), 8.07 - 8.02 (m, 2H), 7.98 (dd, J = 5.2, 2.0 Hz, 1H), 7.94 (d, J = 8.8 Hz, 1H), 7.54 (d, J = 8.4 Hz, 2H), 7.45 - 7.36 (m, 5H), 7.32 (dd, J = 7.6, 2.0 Hz, 1H), 6.66 (dd, J = 16.4, 10.0 Hz, 1H), 6.48 (dd, J = 7.6, 4.8 Hz, 1H), 6.15 (d, J = 16.8 Hz, 1H), 5.98 (d, J = 10.0 Hz, 1H), 4.06 - 3.95 (m, 1H), 3.71 - 3.65 (m, 1H), 3.57 - 3.53 (m, 1H), 3.51 - 3.44 (m, 2H), 2.90 - 2.84 (m, 1H), 2.71 - 2.64 (m, 1H), 2.34 - 2.26 (m, 1H), 2.24 - 2.17 (m, 1H), 1.36 (d, J = 6.4 Hz, 3H). [00676] Example 119: 3-(5-Phenyl-3-(4-(((1S,4S)-5-(vinylsulfonyl)-2,5- diazabicyclo[2.2.1]heptan-2-yl)methyl)phenyl)-3H-imidazo[4,5 -b]pyridin-2-yl)pyridin-2-amine [00677] Example 119 was prepared in a manner similar to Example 4. MS: m/z = 564.3 [M+H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4 J = 8.4 Hz, 1H), 8.05 - 8.02 (m, 2H), 7.98 (dd, J = 5.2, 1.6 Hz, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.57 (d, J = 8.3 Hz, 2H), 7.47 - 7.36 (m, 5H), 7.33 (dd, J = 7.6, 2.0 Hz, 1H), 6.74 (dd, J = 16.8, 10.0 Hz, 1H), 6.48 (dd, J = 7.6, 4.8 Hz, 1H), 6.20 (d, J = 16.8 Hz, 1H), 6.08 (d, J = 10.0 Hz, 1H), 4.27 - 4.21 (m, 1H), 3.95 - 3.83 (m, 2H), 3.66 - 3.62 (m, WSGR Docket No.62619-716.601 1H), 3.58 (d, J = 10.0 Hz, 1H), 3.16 (dd, J = 9.6, 2.0 Hz, 1H), 2.95- 2.83 (m, 2H), 2.00 - 1.92 (m, 1H), 1.77 - 1.68 (m, 1H). [00678] Example 120: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-morpholino-3H-imidazo[4,5 - b]pyridin-3-yl)benzyl)piperidin-4-yl)acrylamide [00679] Example 120 was prepared in a manner similar to Example 2. MS: m/z = 539.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 8.01 (d, J = 7.6 Hz, 1H), 7.98 (d, J = 8.8 Hz, 1H), 7.93 (dd, J = 4.8, 1.6 Hz, 1H), 7.41 (d, J = 8.0 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 7.03 (br s, 2H), 6.98 (dd, J = 7.6, 1.6 Hz, 1H), 6.89 (d, J = 8.8 Hz, 1H), 6.30 (dd, J = 7.6, 4.8 Hz, 1H), 6.23 (dd, J = 17.2, 10.0 Hz, 1H), 6.05 (dd, J = 17.2, 2.4 Hz, 1H), 5.56 (dd, J = 10.0, 2.4 Hz, 1H), 3.70 - 3.65 (m, 4H), 3.64 - 3.58 (m, 1H), 3.53 (s, 2H), 3.42 - 3.38 (m, 4H), 2.82 - 2.74 (m, 2H), 2.09 - 2.03 (m, 2H), 1.80 - 1.74 (m, 2H), 1.49 - 1.38 (m, 2H). [00680] Example 121: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-(4-cyanophenyl)-3H-imidaz o[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)acrylamide [00681] CH ₂ Cl ₂ mixture was stirred at 0 °C for 2 hr. The reaction mixture was concentrated under reduced pressure. After purification by prep phase: [water (NH ₄ HCO ₃ ) - ACN]; B%: 26% - 56%, 14 min), N-(1-(4-(2-(2-aminopyridin-3-yl)- 5-(4-cyanophenyl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piper idin-4-yl)acrylamide (Example 121, 8 mg, yield: 7%) was obtained as a light-yellow solid. MS: m/z = 555.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ 8.26 (d, J = 2.8 Hz, 1H), 8.24 (d, J = 2.8 Hz, 1H), 8.05 (d, J = 8.4 Hz, 1H), 8.01 - 7.97 (m, 1H), 7.81 - 7.77 (m, 2H), 7.58 - 7.52 (m, 2H), 7.46 (d, J = 8.0 Hz, 2H), 7.39 - 7.26 (m, 2H), 6.47 (dd, J = 7.6, 5.2 Hz, 1H), 6.27 - 6.20 (m, 2H), 5.66 - 5.62 (m, 1H), 3.82 - 3.73 WSGR Docket No.62619-716.601 (m, 1H), 3.65 (s, 2H), 3.01 - 2.89 (m, 2H), 2.27 - 2.18 (m, 2H), 1.95 - 1.88 (m, 2H), 1.63 - 1.54 (m, 2H). [00682] Example 122: N-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)piperazin-1-yl)acrylamide [00683] ₂ Cl ₂ (3 mL) were was stirred at 0 °C for 0.5 hr. The mixture was quenched with water (10 mL) at 0 °C and extracted with EtOAc (20 mL x 3). The combined organic layers were washed with brine (30 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. After purification by prep-HPLC (column: Phenomenex C1875 x 30 mm x 3 m; mobile phase: [water (NH3H2O + NH4HCO3) - ACN]; gradient: 35% - 65% B over 8 min), N-(4-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazin-1-yl)acrylamide (Example 122, 21.8 mg, yield: 22%) was obtained as an off-white solid. MS: m/z = 531.2 [M + H]+.1H NMR (400 MHz, Methanol-d4 8.18 (d, J = 8.4 Hz, 1H), 8.03 (d, J = 7.2 Hz, 2H), 7.98 (dd, J = 5.2, 2.0 Hz, 1H), 7.93 (d, J = 8.4 Hz, 1H), 7.54 (d, J = 8.0 Hz, 2H), 7.47 - 7.34 (m, 5H), 7.31 (dd, J = 7.6, 1.6 Hz, 1H), 6.47 (dd, J = 7.6, 5.2 Hz, 1H), 6.35 - 6.24 (m, 1H), 6.21 - 6.11 (m, 1H), 5.70 (dd, J = 10.4, 1.6 Hz, 1H), 3.65 (s, 2H), 2.99 - 2.51 (m, 8H). [00684] Example 123: 1-((3aR,6aS)-5-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imida zo[4,5- b]pyridin-3-yl)benzyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl )prop-2-en-1-one [00685] To a solution of Intermediate 77 (100 mg, 205 mol) in CH2Cl2 (1 mL) were added TEA (62.0 mg, 615 mol) and acryloyl chloride (19.0 mg, 205 mol). The mixture was stirred at 0 °C for 1 hr. The reaction was concentrated. After purification by prep-HPLC (column: Phenomenex C1875 x 30mm x 3 m; mobile phase: [water (NH3H2O + NH4HCO3) - ACN]; B%: 37% - 67%, WSGR Docket No.62619-716.601 8min), 1-((3aR,6aS)-5-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imida zo[4,5-b]pyridin-3- yl)benzyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)prop-2-en-1 -one (Example 123, 7.4 mg, yield: 6.7%) was obtained as an off white solid. MS: m/z = 542.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 J = 8.8 Hz, 1H), 8.08 - 8.03 (m, 2H), 8.00 (dd, J = 4.8, 1.6 Hz, 1H), 7.96 (d, J = 8.4 Hz, 1H), 7.55 (d, J = 8.4 Hz, 2H), 7.48 - 7.42 (m, 4H), 7.42 - 7.37 (m, 1H), 7.34 (dd, J = 7.6, 1.6 Hz, 1H), 6.64 (dd, J = 16.8, 10.4 Hz, 1H), 6.50 (dd, J = 7.6, 5.2 Hz, 1H), 6.27 (dd, J = 16.8, 2.0 Hz, 1H), 5.74 (dd, J = 10.4, 2.0 Hz, 1H), 3.89 - 3.81 (m, 1H), 3.76 (s, 2H), 3.74-3.68 (m, 1H), 3.65 - 3.54 (m, 2H), 3.09 - 2.92 (m, 2H), 2.87 - 2.78 (m, 2H), 2.63 - 2.55 (m, 2H). [00686] Example 124: 3-(3-(4-(((3R,5R)-3,5-Dimethyl-4-(vinylsulfonyl)piperazin-1- yl)methyl)phenyl)-5-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyr idin-2-amine [00687] Example 124 was prepared in a manner similar to Example 4. MS: m/z = 580.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 J = 8.4 Hz, 1H), 8.06 - 7.97 (m, 4H), 7.51 - 7.36 (m, 7H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 7.04 (s, 2H), 6.86 (dd, J = 16.4, 10.8 Hz, 1H), 6.38 (dd, J = 7.6, 2.0 Hz, 1H), 6.11 (d, J = 16.4 Hz, 1H), 6.03 (d, J = 10.8 Hz, 1H), 3.86 - 3.76 (m, 2H), 3.65 (d, J = 13.6 Hz, 1H), 3.48 (d, J = 13.6 Hz, 1H), 3.30 (s, 2H), 2.31 - 2.23 (m, 2H), 1.26 (d, J = 6.4 Hz, 6H). [00688] Example 125: 3-(3-(4-(((3S,5R)-3,5-Dimethyl-4-(vinylsulfonyl)piperazin-1- yl)methyl)phenyl)-5-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyr idin-2-amine [00689] Example 125 was prepared in a manner similar to Example 4. MS: m/z = 580.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ J = 8.0 Hz, 1H), 8.07 - 7.97 (m, 4H), 7.55 - 7.51 (m, 2H), 7.48 - 7.37 (m, 5H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 7.07 (s, 2H), 6.83 (dd, J = 16.4, 10.0 Hz, 1H), 6.38 (dd, J = 8.0, 4.8 Hz, 1H), 6.05 (d, J = 16.4 Hz, 1H), 5.96 (d, J = 10.0 WSGR Docket No.62619-716.601 Hz, 1H), 3.89 - 3.81 (m, 2H), 3.58 (s, 2H), 2.61 (d, J = 11.6 Hz, 2H), 2.14 - 2.10 (m, 2H), 1.36 (d, J = 6.8 Hz, 6H). [00690] Example 126: 3-(3-(4-(((3S,5S)-3,5-Dimethyl-4-(vinylsulfonyl)piperazin-1- yl)methyl)phenyl)-5-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyr idin-2-amine [00691] Example 126 was prepared in a manner similar to Example 4. MS: m/z = 580.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 J = 8.4 Hz, 1H), 8.06 - 7.97 (m, 4H), 7.51 - 7.37 (m, 7H), 7.15 (dd, J = 7.2, 1.2 Hz, 1H), 7.04 (s, 2H), 6.86 (dd, J = 16.4, 9.6 Hz, 1H), 6.38 (dd, J = 7.2, 4.8 Hz, 1H), 6.11 (d, J = 16.4 Hz, 1H), 6.03 (d, J = 9.6 Hz, 1H), 3.86 - 3.77 (m, 2H), 3.65 (d, J = 13.6 Hz, 1H), 3.48 (d, J = 13.6 Hz, 1H), 3.30 (s, 2H), 2.31 - 2.21 (m, 2H), 1.26 (d, J = 6.4 Hz, 6H). [00692] Example 127: 3-(5-Phenyl-3-(4- ((8-(vinylsulfonyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl )phenyl)-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine [00693] Example 127 was prepared in a manner similar to Example 4. MS: m/z = 578.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 J = 8.4 Hz, 1H), 8.04 - 7.97 (m, 4H), 7.50 - 7.40 (m, 7H), 7.13 (dd, J = 8.0, 1.6 Hz, 1H), 7.04 (s, 2H), 6.84 (dd, J = 16.4, 10.0 Hz, 1H), 6.38 (dd, J = 7.6, 4.8 Hz, 1H), 6.14 (d, J = 16.4 Hz, 1H), 6.02 (d, J = 10.0 Hz, 1H), 4.03 (s, 2H), 3.63 (s, 2H), 2.75 - 2.69 (m, 2H), 2.32 - 2.27 (m, 2H), 1.87 - 1.78 (m, 4H). [00694] Example 128: 3-(5-Phenyl-3-(4-((3-(vinylsulfonyl)-3,8-diazabicyclo[3.2.1] octan-8- yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-am ine WSGR Docket No.62619-716.601 [00695] To a solution of Intermediate 30 (60 mg, 123 µmol) and TEA (62 mg, 615 µmol123 µmol) in CH2Cl2 (10 mL) was added dropwise a solution of 2-chloroethane-1-sulfonyl chloride (26 mg, 160 µmol) in CH2Cl2 (5 mL) at 0 °C. The reaction mixture was stirred at 0 °C for 1 hr. The reaction mixture was quenched with saturated NaHCO ₃ (aq) (10 mL) at 0 °C and extracted with CH2Cl2 (20 mL x 2). The combined organic layers were washed with brine (50 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The crude was purified by silica gel flash chromatography (MeOH in CH ₂ Cl ₂ = 0% to 8%), 3-(5-phenyl-3-(4-((3-(vinylsulfonyl)-3,8- diazabicyclo[3.2.1]octan-8-yl)methyl)phenyl)-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine (Example 128, 12.6 mg, yield: 17%) was obtained as an off-white solid. MS: m/z = 578.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ J = 8.4 Hz, 1H), 8.05 - 7.96 (m, 4H), 7.53 (d, J = 8.4 Hz, 2H), 7.49 - 7.43 (m, 4H), 7.42 - 7.37 (m, 1H), 7.16 (dd, J = 7.6, 2.0 Hz, 1H), 7.00 (s, 2H), 6.83 (dd, J = 16.8, 10.0 Hz, 1H), 6.39 (dd, J = 7.6, 4.4 Hz, 1H), 6.14 - 6.04 (m, 2H), 3.60 (s, 2H), 3.28 - 3.25 (m, 2H), 3.21 - 3.17 (m, 2H), 2.87 (d, J = 10.0 Hz, 2H), 2.04 - 1.98 (m, 2H), 1.73 - 1.64 (m, 2H). [00696] Example 129: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)azepan-3-yl)ethenesulfonamide [00697] Example 129 was prepared in a manner similar to Example 4. MS: m/z = 580.4 [M + H] ⁺ . 1H NMR (400 MHz, Dimethylsulfoxide-d ₆ J = 8.0 Hz, 1H), 8.04 (d, J = 7.6 Hz, 2H), 8.02 - 7.97 (m, 2H), 7.51 (d, J = 8.0 Hz, 2H), 7.48 - 7.36 (m, 5H), 7.22 (d, J = 8.0 Hz, 1H), 7.16 (dd, J = 8.0, 2.4 Hz, 1H), 7.04 (s, 2H), 6.53 (dd, J = 16.4, 10.0 Hz, 1H), 6.39 (dd, J = 7.6, 4.4 Hz, 1H), 5.89 (d, J = 16.4 Hz, 1H), 5.77 (d, J = 10.0 Hz, 1H), 3.76 (d, J = 14.0 Hz, 1H), 3.69 (d, J = 14.0 Hz, 1H), 3.29 - 3.20 (m, 1H), 2.83 (dd, J = 13.6, 4.4 Hz, 1H), 2.71 - 2.65 (m, 1H), 2.58 - 2.53 (m, 2H), 1.92 - 1.80 (m, 1H), 1.72 - 1.60 (m, 2H), 1.59 - 1.47 (m, 3H). WSGR Docket No.62619-716.601 [00698] Example 130: 3-(5-Phenyl-3-(4-(((3aR,6aS)-5-(vinylsulfonyl)hexahydropyrro lo[3,4- c]pyrrol-2(1H)-yl)methyl)phenyl)-3H-imidazo[4,5-b]pyridin-2- yl)pyridin-2-amine [00699] Example 130 was prepared in a manner similar to Example 4. MS: m/z = 578.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 J = 8.4 Hz, 1H), 8.05 - 7.97 (m, 4H), 7.50 - 7.43 (m, 6H), 7.42 - 7.37 (m, 1H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.02 (s, 2H), 6.87 (dd, J = 16.4, 10.0 Hz, 1H), 6.39 (dd, J = 8.0, 5.2 Hz, 1H), 6.17 (d, J = 10.0 Hz, 1H), 6.12 (d, J = 16.8 Hz, 1H), 3.66 (s, 2H), 2.92 (dd, J = 10.0, 3.6 Hz, 2H), 2.85 - 2.78 (m, 2H), 2.59 - 2.52 (m, 4H), 2.43 - 2.39 (m, 2H). [00700] Example 131: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)piperidin-4-yl)-N-ethylacrylamide [00701] CH ₂ Cl ₂ (5 mL) was added Et ₃ 25 °C for 1 hr. The reaction mixture was poured into H2O (20 mL). The aqueous phase was extracted with CH ₂ Cl ₂ (20 mL x 2). The combined organic layers were washed with brine (20 mL x 2), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. After purification by prep-TLC (100% EtOAc), N-(1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)piperidin-4-yl)-N-ethylacrylamide (Example 131, 9.5 mg, yield: 16%) was obtained as a yellow solid. MS: m/z = 558.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ J = 8.4 Hz, 1H), 8.03 (d, J = 7.6 Hz, 2H), 8.00 - 7.97 (m, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.57 - 7.33 (m, 8H), 6.80 - 6.65 (m, 1H), 6.52 - 6.43 (m, 1H), 6.34 - 6.12 (m, 1H), 5.81 - 5.67 (m, 1H), 4.42 - 4.35 (m, 0.5H), 3.95 - 3.78 (m, 0.5H), 3.64 (s, 2H), 3.46 - 3.40 (m, 2H), 3.10 - 3.02 (m, 2H), 2.24 - 2.15 (m, 2H), 1.96 - 1.82 (m, 2H), 1.75 - 1.64 (m, 2H), 1.26 - 1.18 (m, 3H). WSGR Docket No.62619-716.601 [00702] Example 132: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)piperidin-4-yl)-N-(cyanomethyl)acrylamide [00703] Step 1: 2-((1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b] pyridin-3- yl)benzyl)piperidin-4-yl)amino)acetonitrile [00704] To a solution of Intermediate 3 (2.0 g HCl salt, 3.55 mmol) in DMF (20 mL) were added K2CO3 (1.5 g, 10.6 mmol) and 2-bromoacetonitrile (426 mg, 3.55 mmol). The mixture was stirred at 25 °C for 16 hr. The reaction mixture was diluted with H2O (30 mL) and extracted with EtOAc (30 mL x 2). The combined organic layers were washed with brine (50 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. After purification by silica gel flash chromatography (MeOH in CH2Cl2 = 0% to 6%), 2-((1-(4-(2-(2-aminopyridin-3-yl)-5- phenyl-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)a mino)acetonitrile (Intermediate 132, 613 mg, yield: 34%) was obtained as a light yellow solid. MS: m/z = 515.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4 J = 8.4 Hz, 1H), 8.05 - 8.00 (m, 2H), 7.97 (dd, J = 5.2, 1.6 Hz, 1H), 7.92 (d, J = 8.4 Hz, 1H), 7.54 - 7.49 (m, 2H), 7.44 - 7.34 (m, 5H), 7.29 (dd, J = 7.6, 4.8 Hz, 1H), 6.45 (dd, J = 7.6, 4.8 Hz, 1H), 3.66 (s, 2H), 3.62 (s, 2H), 2.99 - 2.89 (m, 2H), 2.72 - 2.63 (m, 1H), 2.21 - 2.13 (m, 2H), 1.93 - 1.88 (m, 2H), 1.50 - 1.40 (m, 2H). [00705] Step 2: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)piperidin-4-yl)-N-(cyanomethyl)acrylamide [00706] To a solution of 2-((1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b] pyridin- in CH2Cl2 at 0 °C for 1 hr. The mixture was added H2O (5 mL) and extracted with EtOAc (10 mL x 2). The combined organic layers were washed with brine (20 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purification by prep-TLC (CH2Cl2 in MeOH = 10%), N-(1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)piperidin-4-yl)-N-(cyanomethyl)acrylamide (Example 132, 13.7 mg, yield: 13%) was obtained as a yellow solid. MS: m/z = 569.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4 (d, J = 8.4 Hz, 1H), 8.03 (d, J = 7.6 Hz, 2H), 7.98 (dd, J = 4.8, 1.6 Hz, 1H), 7.94 (d, J = 8.0 Hz, 1H), 7.58 - 7.52 (m, 2H), 7.47 - 7.31 (m, 6H), 6.88 - 6.74 (m, 1H), 6.48 (dd, J = 7.2, 5.2 Hz, WSGR Docket No.62619-716.601 1H), 6.37 - 6.27 (m, 1H), 5.84 (d, J = 10.4 Hz, 1H), 4.37 (s, 2H), 4.23 - 3.78 (m, 1H), 3.66 (s, 2H), 3.11 - 3.01 (m, 2H), 2.27 - 2.19 (m, 2H), 2.03 - 1.90 (m, 2H), 1.83 - 1.75 (m, 2H). [00707] Example 133: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin- 3-yl)benzyl)piperidin-4-yl)-N-cyclopropylacrylamide [00708] The reaction mixture was quenched by addition of H ₂ O (5 mL) at 25 °C, then diluted with CH ₂ Cl ₂ (10 mL) and extracted with CH2Cl2 (15 mL x 2). The combined organic layers were washed with brine (15 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purification by prep-TLC (MeOH in CH2Cl2 = 10%), N-(1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)-N-cyclopro pylacrylamide (Example 133, 4.9 mg, yield: 8.6%) was obtained as a yellow solid. MS: m/z = 570.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ J = 8.4 Hz, 1H), 8.05 - 8.01 (m, 2H), 7.98 (dd, J = 4.8, 1.6 Hz, 1H), 7.93 (d, J = 8.4 Hz, 1H), 7.56 - 7.51 (m, 2H), 7.46 - 7.34 (m, 5H), 7.30 (dd, J = 7.6, 1.6 Hz, 1H), 7.01 (dd, J = 16.8, 10.4 Hz, 1H), 6.46 (dd, J = 8.0, 5.2 Hz, 1H), 6.18 (dd, J = 16.8, 2.0 Hz, 1H), 5.68 (dd, J = 10.4, 2.0 Hz, 1H), 4.08 - 3.95 (m, 1H), 3.66 (s, 2H), 3.10 - 3.02 (m, 2H), 2.73 - 2.64 (m, 1H), 2.22 - 2.14 (m, 4H), 1.82 - 1.74 (m, 2H), 1.00 - 0.93 (m, 2H), 0.86 - 0.79 (m, 2H). [00709] Example 134: N-allyl-N-(1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo [4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)acrylamide [00710] Step 1: 3-(3-(4-((4-(Allylamino)piperidin-1-yl)methyl)phenyl)-5-phen yl-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine WSGR Docket No.62619-716.601 [00711] 2CO ₃ stirred at 25 °C for 16 hr. The mixture was filtered. The filtrate was purified by prep-HPLC (column: Waters xbridge 150 x 25 mm 10 um; mobile phase: [water (NH4HCO3) - ACN]; gradient: 35% - 65% B over 18 min), 3-(3-(4-((4-(allylamino)piperidin-1-yl)methyl)phenyl)-5- phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (10.3 mg, yield: 9.3%) was obtained as a light-yellow lyophilized powder. MS: m/z = 516.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol- d ₄ ) J = 8.4 Hz, 1H), 8.05 - 8.01 (m, 2H), 7.98 (dd, J = 4.8, 1.6 Hz, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.55 - 7.51 (m, 2H), 7.46 - 7.36 (m, 5H), 7.33 (dd, J = 7.6, 1.6 Hz, 1H), 6.47 (dd, J = 7.6, 4.8 Hz, 1H), 5.99 - 5.80 (m, 1H), 5.27 (d, J = 17.2 Hz, 1H), 5.18 (d, J = 10.8 Hz, 1H), 3.62 (s, 2H), 3.34 - 3.30 (m, 2H), 3.05 - 2.90 (m, 2H), 2.72 - 2.55 (m, 1H), 2.18 - 2.08 (m, 2H), 1.99 - 1.90 (m, 2H), 1.59 - 1.40 (m, 2H). [00712] Step 2: N-allyl-N-(1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo [4,5-b]pyridin-3- yl)benzyl)piperidin-4-yl)acrylamide [00713] To a solution of 3-(3-(4-((4-(allylamino)piperidin-1-yl)methyl)phenyl)-5-phen yl-3H- 1 hr. The mixture was quenched with H2O (10 mL), and then extracted with CH2Cl2 (15 mL x 2). The combined organic layers were washed with brine (10 mL x 2), dried over Na2SO4, filtered and concentrated under reduced pressure. After purification by silica gel flash chromatography (MeOH in CH2Cl2 = 0% to 5%), N-allyl-N-(1-(4-(2-(2-aminopyridin-3-yl)-5- phenyl-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)a crylamide (Example 134, 10 mg, yield: 10%) was obtained as a red solid. MS: m/z = 570.5 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4 8.19 (d, J = 8.4 Hz, 1H), 8.06 - 8.01 (m, 2H), 7.98 (dd, J = 5.2, 2.0 Hz, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.56 - 7.50 (m, 2H), 7.47 - 7.35 (m, 5H), 7.32 (dd, J = 7.6, 1.6 Hz, 1H), 6.89 - 6.53 (m, 1H), 6.47 (dd, J = 7.6, 5.2 Hz, 1H), 6.31 - 6.14 (m, 1H), 5.96 - 5.82 (m, 1H), 5.75 - 5.70 (m, 1H), 5.26 - 5.06 (m, 2H), 4.53 - 4.38 (m, 1H), 4.03 (s, 2H), 3.64 (s, 2H), 3.10 - 3.02 (m, 2H), 2.30 - 2.11 (m, 2H), 1.96 - 1.67 (m, 4H). [00714] Example 135: 1-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)piperidin-4-yl)-1,5-dihydro-2H-pyrrol-2-one WSGR Docket No.62619-716.601 [00715] 2Cl2 (100 mL) was added Ti(Oi-Pr) _{4 2} Cl ₂ (20 mL). The mixture was stirred at 25 °C for 0.5 hr under N _{2 2} Cl ₂ (20 mL) was added into the mixture, and the reaction mixture was stirred at 40 °C for 16 hr under N2 atmosphere. The mixture was diluted with H ₂ O (100 mL) and extracted with CH ₂ Cl ₂ (100 mL x 2). The combined organic layers were washed with brine (100 mL x 2), dried over Na2SO4, filtered and concentrated under reduced pressure. After purification by silica gel flash chromatography (MeOH in CH ₂ Cl ₂ = 0% to 10%) and purified again by prep-HPLC (column: Waters xbridge 150 x 25 mm x 10 um; mobile phase: [water (NH4HCO3) - ACN]; gradient: 29% - 59% B over 18 min), 1-(1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)piperidin-4-yl)-1,5-dihydro-2H-pyrrol-2-one (Example 135, 9.6 mg, yield: 5.3%) was obtained as an off-white lyophilized powder. MS: m/z = 542.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4 8.20 (d, J = 8.4 Hz, 1H), 8.04 (d, J = 7.2 Hz, 2H), 7.98 (dd, J = 5.2, 1.6 Hz, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.55 (d, J = 8.4 Hz, 2H), 7.48 - 7.36 (m, 5H), 7.35 - 7.28 (m, 2H), 6.48 (dd, J = 7.6, 4.8 Hz, 1H), 6.22 - 6.05 (m, 1H), 4.13 (s, 2H), 4.05 - 3.94 (m, 1H), 3.66 (s, 2H), 3.20 - 3.00 (m, 2H), 2.31 - 2.21 (m, 2H), 1.92 - 1.78 (m, 4H). [00716] Example 136: N-(1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)piperidin-4-yl)-N-(but-3-en-1-yl)acrylamide [00717] Step 1: 3-(3-(4-((4-(But-3-en-1-ylamino)piperidin-1-yl)methyl)phenyl )-5-phenyl-3H- imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00718] 2CO3 at 25 °C for 12 hr, and then stirred at 60 °C for 12 hr. The reaction mixture was diluted with H ₂ O (30 mL) and extracted with EtOAc (30 mL x 2). The combined organic layers were washed with brine (30 mL x 2), dried over Na2SO4, filtered and concentrated under reduced pressure. After purification by prep-HPLC (column: Welch Ultimate C18150 x 25 mm x 5 um; mobile phase: [water (HCl) - ACN]; gradient: 2% - 32% B over 10 min), 3-(3-(4-((4-(but-3-en- 1-ylamino)piperidin-1-yl)methyl)phenyl)-5-phenyl-3H-imidazo[ 4,5-b]pyridin-2-yl)pyridin-2- amine (13 mg, yield: 10%) was obtained as a light-yellow solid. MS: m/z = 530.3 [M + H] ⁺ . ¹ H WSGR Docket No.62619-716.601 NMR (400 MHz, Methanol-d4) J = 8.4 Hz, 1H), 8.09 - 8.01 (m, 4H), 7.93 - 7.85 (m, 3H), 7.74 (d, J = 8.4 Hz, 2H), 7.49 - 7.39 (m, 3H), 6.95 - 6.89 (m, 1H), 5.87 - 5.80 (m, 1H), 5.33 - 5.24 (m, 1H), 5.23 - 5.13 (m, 1H), 4.52 (s, 2H), 3.75 - 3.71 (m, 2H), 3.63 - 3.52 (m, 1H), 3.29 - 3.25 (m, 2H), 3.19 - 3.15 (m, 2H), 2.63 - 2.34 (m, 4H), 2.24 - 2.02 (m, 2H). [00719] Step 2: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)piperidin-4-yl)-N-(but-3-en-1-yl)acrylamide [00720] To a solution of 3-(3-(4-((4-(but-3-en-1-ylamino)piperidin-1-yl)methyl)phenyl )-5- phenyl-3H was stirred at 0 °C for 1 hr. The mixture was quenched with H2O (10 mL) and extracted with CH ₂ Cl ₂ (15 mL x 2). The combined organic layers were washed with brine (10 mL x 2), dried over Na2SO4, filtered and concentrated under reduced pressure. After purification by silica gel flash chromatography (MeOH in CH2Cl2 = 0% to 5%), N-(1-(4-(2-(2-aminopyridin-3-yl)-5- phenyl-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)- N-(but-3-en-1-yl)acrylamide (Example 136, 17.8 mg, yield: 15%) was obtained as a yellow solid. MS: m/z = 584.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4 8.19 (d, J = 8.4 Hz, 1H), 8.03 (d, J = 6.8 Hz, 2H), 7.98 (dd, J = 4.8, 1.6 Hz, 1H), 7.94 (d, J = 8.0 Hz, 1H), 7.57 - 7.51 (m, 2H), 7.48 - 7.36 (m, 5H), 7.35 - 7.32 (m, 1H), 6.87 - 6.62 (m, 1H), 6.48 (dd, J = 7.6, 4.8 Hz, 1H), 6.33 - 6.11 (m, 1H), 5.89 - 5.67 (m, 2H), 5.17 - 5.01 (m, 2H), 4.41 – 3.99 (m, 0.5H), 3.93 – 3.83 (m, 0.5H), 3.65 (s, 2H), 3.44 - 3.36 (m, 2H), 3.10 - 2.98 (m, 2H), 2.43 - 2.29 (m, 2H), 2.24 - 2.13 (m, 2H), 1.97 - 1.85 (m, 2H), 1.77 - 1.67 (m, 2H). [00721] Example 137: 1-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)piperidin-4-yl)-5,6-dihydropyridin-2(1H)-one [00722] ₂ Cl ₂ (30 mL) was added Ti(Oi- Pr)4 2Cl2 (100 mL). The mixture was stirred at 25 °C for 0.5 hr under N _{2 2} Cl ₂ (20 mL) was added into the mixture, and the reaction mixture was stirred at 40 °C for 16 hr under N ₂ atmosphere. The mixture was diluted with H2O (100 mL) and extracted with CH2Cl2 (100 mL x 2). The combined organic layers were washed with brine (100 mL x 2), dried over Na ₂ SO ₄ , filtered and WSGR Docket No.62619-716.601 concentrated under reduced pressure. After purification by silica gel flash chromatography (MeOH in CH ₂ Cl ₂ = 0% to 5%) and purified again by prep-HPLC (column: Waters xbridge 150 x 25 mm x 10 um; mobile phase: [water (NH ₄ HCO ₃ )-ACN]; gradient: 32% - 62% B over 18 min), 1-(1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)piperidin-4-yl)-5,6-dihydropyridin-2(1H)-one (Example 137, 7.6 mg, yield: 5.2%) was obtained as a brown solid. MS: m/z = 556.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4 8.20 (d, J = 8.4 Hz, 1H), 8.05 - 8.00 (m, 2H), 7.98 (dd, J = 5.2, 2.0 Hz, 1H), 7.95 (d, J = 8.0 Hz, 1H), 7.57 - 7.52 (m, 2H), 7.48 - 7.37 (m, 5H), 7.33 (dd, J = 7.6, 1.6 Hz, 1H), 6.71 - 6.66 (m, 1H), 6.48 (dd, J = 7.6, 5.2 Hz, 1H), 5.88 - 5.80 (m, 1H), 4.47 - 4.39 (m, 1H), 3.65 (s, 2H), 3.44 - 3.36 (m, 2H), 3.10 - 3.00 (m, 2H), 2.40 - 2.36 (m, 2H), 2.24 - 2.18 (m, 2H), 1.92 - 1.82 (m, 2H), 1.66 - 1.60 (m, 2H). [00723] Example 138: N-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin- 3-yl)benzyl)piperazin-1-yl)-N-methylacrylamide [00724] ₂ Cl ₂ (1 mL) were stirred at 25 °C for 2 hr. The mixture was concentrated. After purification by prep-TLC (MeOH in CH ₂ Cl ₂ = 10%), N-(4-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazin-1-yl)-N-methylacrylamide (Example 138, 4 mg, yield: 11%) was obtained as an off white solid. MS: m/z = 545.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Acetonitrile-d ₃ J = 8.0 Hz, 1H), 8.05 - 7.98 (m, 3H), 7.90 (d, J = 8.8 Hz, 1H), 7.51 (d, J = 8.4 Hz, 2H), 7.48 - 7.37 (m, 5H), 7.24 (dd, J = 17.2, 10.0 Hz, 1H), 7.14 (dd, J = 7.6, 1.6 Hz, 1H), 6.59 (br s, 2H), 6.37 (dd, J = 7.6, 4.8 Hz, 1H), 6.17 (dd, J = 17.6, 2.8 Hz, 1H), 5.59 (dd, J = 10.4, 2.4 Hz, 1H), 3.64 (s, 2H), 3.01 - 2.92 (m, 5H), 2.87 (d, J = 11.6 Hz, 2H), 2.68 (d, J = 10.8 Hz, 2H), 2.39 - 2.29 (m, 2H). [00725] Example 139: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-methyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)piperidin-4-yl)acrylamide WSGR Docket No.62619-716.601 [00726] Example 139 was prepared in a manner similar to Example 1. MS: m/z = 468.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4) (m, 2H), 7.41 - 7.34 (m, 2H), 7.31 - 7.23 (m, 2H), 6.44 (dd, J = 7.6, 5.2 Hz, 1H), 6.28 - 6.18 (m, 2H), 5.64 (dd, J = 7.6, 4.0 Hz, 1H), 3.81 - 3.75 (m, 1H), 3.64 (s, 2H), 2.96 (d, J = 11.6 Hz, 2H), 2.59 (s, 3H), 2.26 - 2.19 (m, 2H), 1.95 - 1.88 (m, 2H), 1.62 - 1.57 (m, 2H). [00727] Example 140: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-morpholino-3H-imidazo[4,5 - b]pyridin-3-yl)benzyl)piperidin-4-yl)-N-methylacrylamide [00728] Example 140 was prepared in a manner similar to Example 3. MS: m/z = 553.3 [M + H] ⁺ . ¹ H NMR(400 MHz, Dimethylsulfoxide-d ₆ J = 7.6 Hz, 2H), 7.30 (d, J = 7.6 Hz, 2H), 7.03 (br s, 2H), 6.98 (d, J = 7.2 Hz, 1H), 6.88 (d, J = 8.8 Hz, 1H), 6.81 - 6.66 (m, 1H), 6.30 (t, J = 6.4 Hz, 1H), 6.06 (t, J = 14.8 Hz, 1H), 5.65 (t, J = 7.6 Hz, 1H), 4.35 - 4.25 (m, 0.5H), 3.80 - 3.72 (m, 0.5H), 3.72 - 3.62 (m, 4H), 3.54 (s, 2H), 3.42 - 3.35 (m, 4H), 2.89 (s, 3H), 2.80 - 2.65 (m, 2H), 2.12 - 2.05 (m, 2H), 1.86 - 1.67 (m, 2H), 1.59 - 1.43 (m, 2H). [00729] Example 141: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-cyclopropyl-3H-imidazo[4, 5- b]pyridin-3-yl)benzyl)piperidin-4-yl)-N-methylacrylamide [00730] 2CO ₃ (503 mg, 3.64 mmol). The mixture was stirred at 50 °C for 2 hr. The resulting mixture was extracted with EtOAc (20 mL x WSGR Docket No.62619-716.601 3). The combined organic layers were washed with brine (30 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. After purification by silica gel flash chromatography (MeOH in CH ₂ Cl ₂ = 0% to 6%), N-(1-(4-(2-(2-aminopyridin-3-yl)-5-cyclopropyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)-N-methylac rylamide (Example 141, 30 mg, yield: 27%) was obtained as a yellow solid. MS: m/z = 508.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4 J = 8.0 Hz, 2H), 7.34 (d, J = 8.4 Hz, 2H), 7.29 - 7.21 (m, 2H), 6.84 - 6.67 (m, 1H), 6.45 (dd, J = 7.6, 5.2 Hz, 1H), 6.25 - 6.12 (m, 1H), 5.79 - 5.68 (m, 1H), 4.51 - 4.40 (m, 0.6H), 3.93 - 3.84 (m, 0.4H), 3.63 (s, 2H), 3.04 - 3.00 (m, 4H), 2.90 - 2.89 (m, 1H), 2.25 - 2.12 (m, 3H), 2.01 - 1.81 (m, 2H), 1.73 - 1.59 (m, 2H), 0.99 - 0.89 (m, 4H). [00731] Example 142: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-morpholino-3H-imidazo[4,5 - b]pyridin-3-yl)benzyl)piperidin-4-yl)-N-(methyl-d3)acrylamid e [00732] Step 1: tert-Butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-morpholino-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperidin-4-yl)(methyl-d ₃ )carbamate [00733] To a mixture of 3-(3-(4-(chloromethyl)phenyl)-5-morpholino-3H-imidazo[4,5- b]pyridin-2-yl)pyridin-2-amine (refer to Intermediate 80 for detail procedures, 1 g, 2.38 mmol) and tert-butyl (methyl-d ₃ )(piperidin-4-yl)carbamate (refer to Intermediate 70 for detail K2CO3 (3.28 g, 23.7 mmol). The mixture was stirred at 80 °C for 2 hr. The reaction mixture was diluted with H ₂ O (30 mL), filtered and concentrated under reduced pressure. After purification by silica gel flash chromatography (MeOH in CH ₂ Cl ₂ = 0% to 7%), tert-butyl (1-(4- (2-(2-aminopyridin-3-yl)-5-morpholino-3H-imidazo[4,5-b]pyrid in-3-yl)benzyl)piperidin-4- yl)(methyl-d ₃ )carbamate (700 mg, yield: 47%) was obtained as a yellow solid. MS: m/z = 602.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Chloroform-d J = 4.8 Hz, 1H), 7.90 (d, J = 9.2 Hz, WSGR Docket No.62619-716.601 1H), 7.42 (d, J = 8.0 Hz, 2H), 7.29 (d, J = 8.0 Hz, 2H), 6.99 (d, J = 7.6 Hz, 1H), 6.69 (d, J = 8.8 Hz, 1H), 6.51 (br s, 2H), 6.31(d, J = 7.6, 4.8 Hz, 1H), 4.12 - 3.92 (m, 1H), 3.83 - 3.77 (m, 4H), 3.58 (s, 2H), 3.55 - 3.45 (m, 4H), 3.05 - 2.95 (m, 2H), 2.25 - 2.05 (m, 2H), 180 - 1.70 (m, 2H), 1.70 - 1.60 (m, 2H), 1.46 (s, 9H). [00734] Step 2: 3-(3-(4-((4-((Methyl-d ₃ )amino)piperidin-1-yl)methyl)phenyl)-5-morpholino- 3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine [00735] To a mixture of tert-butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-morpholino-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4-yl)(methyl-d ₃ )carbamate (700 mg, 1.16 mmol) in CH2Cl2 (10 mL) was added HCl/1,4-dioxane (4 M, 5 mL), then the mixture was stirred at 20 °C for 2 hr. The reaction mixture was diluted with H2O (50 mL) and extracted with CH2Cl2 (20 mL x 3). The aqueous phase was neutralized by addition saturated NaHCO ₃ (100 mL), and then extracted with CH2Cl2 (50 mL x 6). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure, 3-(3-(4-((4-((methyl-d3)amino)piperidin-1- yl)methyl)phenyl)-5-morpholino-3H-imidazo[4,5-b]pyridin-2-yl )pyridin-2-amine (518.8 mg, yield: 82%) was obtained as a white powder. MS: m/z = 502.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 J = 8.8 Hz, 1H), 7.93 (dd, J = 4.4, 1.2 Hz, 1H), 7.40 (d, J = 8.0 Hz, 2H), 7.29 (d, J = 8.0 Hz, 2H), 7.03 (br s, 2H), 6.98 (dd, J =8.0, 1.6 Hz, 1H), 6.89 (d, J = 8.8 Hz, 1H), 6.30 (dd, J = 7.6, 4.4 Hz, 1H), 3.70 - 3.64 (m, 4H), 3.50 (s, 2H), 3.41 - 3.37 (m, 4H), 2.80 - 2.70 (m, 2H), 2.27 - 2.20 (m, 1H), 2.20 - 1.94 (m, 2H), 1.80 - 1.71 (m, 2H), 1.25 - 1.15 (m, 2H). [00736] Step 3: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-morpholino-3H-imidazo[4,5 -b]pyridin-3- yl)benzyl)piperidin-4-yl)-N-(methyl-d3)acrylamide [00737] To a mixture of 3-(3-(4-((4-((methyl-d ₃ )amino)piperidin-1-yl)methyl)phenyl)-5- morpholino-3H-imidazo[4,5-b dropwise. The mixture was stirred at 0 °C for 0.5 hr. The reaction mixture was quenched with H2O (30 mL) at 0 °C and extracted with CH2Cl2 (20 mL x 3). The combined organic layers were washed with H2O (30 mL x 2), dried over Na2SO4, filtered and concentrated under reduced pressure. After purification by silica gel flash chromatography (MeOH in CH ₂ Cl ₂ = 0% to 7%), and then triturated with CH3CN at 20 °C for 5 min, N-(1-(4-(2-(2-aminopyridin-3-yl)-5- morpholino-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperidin-4- yl)-N-(methyl-d3)acrylamide (Example 142, 28.9 mg, yield: 8.5%) was obtained as an off-white powder. MS: m/z = 556.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 J = 8.8 Hz, 1H), 7.94 (dd, J = 8.8, 1.6 Hz, 1H), 7.43 (d, J = 8.0 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H), 7.03 (br s, 2H), 6.98 (dd, J = 7.6, 1.6 Hz, 1H), 6.90 (d, J = 8.8 Hz, 1H), 6.80 - 6.69 (m, 1H), 6.31 (dd, J = 7.6, 4.8 Hz, 1H), 6.12 - WSGR Docket No.62619-716.601 6.03 (m, 1H), 5.69 - 5.62 (m, 1H), 3.85 - 3.66 (m, 5H), 3.56 (s, 2H), 3.42 - 3.39 (m, 4H), 2.92 - 2.86 (m, 2H), 2.12 - 2.03 (m, 2H), 1.84 - 1.70 (m, 2H), 1.58 - 1.46 (m, 2H). [00738] Example 143: 1-(2-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin- 3-yl)benzyl)-2,7-diazaspiro[3.5]nonan-7-yl)but-2-yn-1-one [00739] To a solution of Intermediate 23 (80 mg, 159 mmol) and TEA (32.3 mg, 319 mmol) in DMF (1.0 mL) were added but-2-ynoic acid (17.4 mg, 207 mmol), EDCI (45.9 mg, 239 mmol) and DMAP (1.95 mg, 15.9 mmol). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was filtered. After purification by prep-HPLC (column: [water (NH4HCO3) - ACN]; B%: 28% - 58%, 18 min), 1-(2-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin- 3-yl)benzyl)-2,7-diazaspiro[3.5]nonan-7-yl)but-2-yn-1-one (Example 143, 18.6 mg, yield: 20%) was obtained as a yellow solid. MS: m/z = 568.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4 8.19 (d, J = 8.4 Hz, 1H), 8.06 - 7.92 (m, 4H), 7.53 - 7.31 (m, 8H), 6.48 (dd, J = 7.6, 4.8 Hz, 1H), 3.80 (s, 2H), 3.76 - 3.70 (m, 2H), 3.57 - 3.51 (m, 2H), 3.27 - 3.21 (m, 4H), 2.03 (s, 3H), 1.87 - 1.80 (m, 2H), 1.79 - 1.72 (m, 2H). [00740] Example 144: 1-((3aR,6aS)-5-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imida zo[4,5- b]pyridin-3-yl)benzyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl )prop-2-yn-1-one [00741] ₂ Cl ₂ (1 mL) were added concentrated. After purification by prep-HPLC (column: Boston Prime C18150 x 30 mm x 5 3H2O + NH4HCO3) - ACN]; gradient:58% - 88% B over 7 min), 1-((3aR,6aS)-5-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imida zo[4,5-b]pyridin-3- yl)benzyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)prop-2-yn-1 -one (Example 144, 16.1 mg, WSGR Docket No.62619-716.601 yield: 15%) was obtained as a yellow solid. MS: m/z = 562.2 [M + Na] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ 8.27 (d, J = 8.0 Hz 1H), 8.04 - 7.97 (m, 5H), 7.49 - 7.41 (m, 6H), 7.15 - 7.13 (m, 1H), 7.03 (br s, 2H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 4.45 (s, 1H), 3.83 - 3.63 (m, 1H), 3.55 - 3.54 (m, 2H), 3.53 - 3.50 (m, 2H), 3.37 - 3.34 (m, 1H), 2.86 - 2.83 (m, 2H), 2.58 - 2.55 (m, 2H), 2.50 - 2.44 (m, 2H). [00742] Example 145: 1-((3aR,6aS)-5-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imida zo[4,5- b]pyridin-3-yl)benzyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl )but-2-yn-1-one [00743] Example 145 was prepared in a manner similar to Example 144. MS: m/z = 554.2 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d ₆ 8.27 (d, J = 8.4 Hz, 1H), 8.05 - 7.97 (m, 4H), 7.49 - 7.39 (m, 7H), 7.16 (dd, J = 8.0, 2.0 Hz, 1H), 7.03 (br s, 2H), 6.39 (dd, J = 7.6, 4.8 Hz, 1H), 3.79 - 3.77 (m, 1H), 3.66 - 3.63 (m, 2H), 3.52 - 3.50 (m, 2H), 3.31 - 3.29 (m, 1H), 2.85 - 2.82 (m, 2H), 2.59 - 2.55 (m, 2H), 2.49 - 2.41 (m, 2H), 1.98 (s, 3H). [00744] Example 146: N-(4-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)piperazin-1-yl)propiolamide [00745] To a solution of 2,4,6-tributyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide (421 mg, 1.17 mmol) in CH2Cl2 (1 mL) and EtOAc (1 mL) were added Intermediate 76 (200 mg, 390 This mixture was stirred at 0 °C for 30 mins. The mixture was concentrated. After purification by prep-HPLC (column: Phenomenex C1875 x 30 mm x 3 m; mobile phase: [water (NH ₃ H ₂ O + NH4HCO3) - ACN]; gradient: 33%-63% B over 8 min), N-(4-(4-(2-(2-aminopyridin-3-yl)-5- phenyl-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)piperazin-1-yl)p ropiolamide (Example 146, 8.0 mg, yield: 3.9%) was obtained as a yellow solid. MS: m/z = 529.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 J = 7.6 Hz, 1H), 8.05 - 7.95 (m, 5H), 7.56 - 7.35 (m, WSGR Docket No.62619-716.601 7H), 7.17 (dd, J = 7.6, 1.6 Hz, 1H), 7.05 (s, 2H), 6.46 - 6.38 (m, 2H), 3.90 - 3.65 (m, 4H), 3.15 - 2.85 (m, 6H). [00746] Example 147: N-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)piperazin-1-yl)but-2-ynamide [00747] filtered and concentrated under reduced pressure. After purification by prep-HPLC (column: Phenomenex C18150 x 25 mm x 10 m; mobile phase: [water (NH4HCO3) - ACN]; gradient: 26% - 56% B over 10 min), N-(4-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazin-1-yl)but-2-ynamide (Example 147, 9.4 mg, yield: 8%) was obtained as a yellow solid. MS: m/z = 543.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d4 (d, J = 8.4 Hz, 1H), 8.05 - 8.01 (m, 2H), 7.98 (dd, J = 5.2, 2.0 Hz, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.60 (d, J = 8.4 Hz, 2H), 7.49 - 7.37 (m, 5H), 7.33 (dd, J = 7.6, 1.6 Hz, 1H), 6.50 (dd, J = 7.6, 4.8 Hz, 1H), 3.97 - 3.89 (m, 2H), 3.81 (s, 2H), 3.20 - 3.14 (m, 2H), 3.06 - 2.99 (m, 2H), 2.91 - 2.82 (m, 2H), 2.37 (d, J = 1.6 Hz, 3H). [00748] Example 148: N-(1-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin- 3-yl)benzyl)piperidin-4-yl)but-2-ynamide [00749] To a solution of Intermediate 3 (150 mg, 293 mmol) and TEA (59.3 mg, 586 mmol) in DMF (1.5 mL) were added but-2-ynoic acid (32.0 mg, 381 mmol), EDCI (84.2 mg, 439 mmol) and DMAP (3.58 mg, 29.3 mmol). The mixture was stirred at 25 °C for 1 hr. The reaction mixture was filtered and the residue was purified by prep-HPLC (column: [water (NH4HCO3) - ACN]; B%: 34% - 64%, 15 min), N-(1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- WSGR Docket No.62619-716.601 b]pyridin-3-yl)benzyl)piperidin-4-yl)but-2-ynamide (Example 148, 63.0 mg, yield: 39%) was obtained as a light yellow solid. MS: m/z = 542.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) 8.19 (dd, J = 8.4, 2.4 Hz, 1H), 8.03 (d, J = 7.2 Hz, 2H), 8.00 - 7.89 (m, 2H), 7.55 - 7.50 (m, 2H), 7.48 - 7.28 (m, 6H), 6.51 - 6.42 (m, 1H), 3.77 - 3.68 (m, 1H), 3.63 (br s, 2H), 3.01 - 2.87 (m, 2H), 2.26 - 2.12 (m, 2H), 1.96 (s, 3H), 1.87 - 1.82 (m, 2H), 1.65 - 1.49 (m, 2H). [00750] Example 149: 1-(8-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin- 3-yl)benzyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)prop-2-yn-1-o ne [00751] concentrated under reduced pressure. After purification by prep-HPLC (column: Waters 4HCO3) - ACN]; gradient: 38% - 68% B over 10 min), 1-(8-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)prop-2-yn-1-one (Example 149, 11.2 mg, 10% yield) was obtained as a light yellow solid. MS: m/z = 540.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 7.47 (m, 2H), 7.42 - 7.37 (m, 2H), 7.34 - 7.23 (m, 1H), 7.19 - 7.15 (m, 1H), 7.03 - 6.98 (m, 2H), 6.41 (dd, J = 8.0, 4.8 Hz, 1H), 4.57 (s, 1H), 4.06 - 3.84 (m, 2H), 3.64 (s, 2H), 2.73 - 2.62 (m, 2H), 2.34 - 2.32 (m, 2H), 2.02 - 1.94 (m, 2H), 1.59 - 1.46 (m, 2H). [00752] Example 150: 1-(8-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)but-2-yn-1-one [00753] WSGR Docket No.62619-716.601 concentrated under reduced pressure. After purification by prep-HPLC (column: Waters 4HCO ₃ ) - ACN]; gradient: 38% - 68% B over 10 min), 1-(8-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)but-2-yn-1-one (Example 150, 31.4 mg, 28% yield) was obtained as a light yellow solid. MS: m/z = 554.4 [M + H] ⁺ . ¹ H NMR (400 MHz, Dimethylsulfoxide-d6 J = 8.0 Hz, 1H), 8.06 - 7.98 (m, 4H), 7.58 - 7.53 (m, 2H), 7.50 - 7.44 (m, 4H), 7.42 - 7.39 (m, 1H), 7.18 (dd, J = 7.6, 2.0 Hz, 1H), 7.00 (br s, 2H), 6.41 (dd, J = 7.6, 4.8 Hz, 1H), 4.03 - 3.94 (m, 2H), 3.63 (s, 2H), 3.29 - 3.24 (m, 2H), 3.21 - 3.18 (m, 1H), 2.88 - 2.82 (m, 1H), 2.02 (s, 3H), 2.00 - 1.95 (m, 2H), 1.56 - 1.41 (m, 2H). [00754] Example 151: 1-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin- 3-yl)benzyl)piperazin-1-yl)but-2-yn-1-one [00755] filtered and concentrated under reduced pressure. After purification by prep-HPLC (column: Phenomenex C18150 x 25 mm x 10 m; mobile phase: [water (NH ₄ HCO ₃ ) - ACN]; gradient: 33% - 63% B over 10 min), 1-(4-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazin-1-yl)but-2-yn-1-one (Example 151, 23 mg, yield: 19%) was obtained as a light yellow powder. MS: m/z = 528.1 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol- d4 J = 8.4 Hz, 1H), 8.06 - 8.01 (m, 2H), 7.99 (dd, J = 4.8, 1.6 Hz, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.57 - 7.53 (m, 2H), 7.47 - 7.41 (m, 4H), 7.40 - 7.36 (m, 1H), 7.32 (dd, J = 7.6, 1.6 Hz, 1H), 6.48 (dd, J = 7.6, 5.2 Hz, 1H), 3.85 - 3.80 (m, 2H), 3.67 (s, 2H), 3.66 - 3.63 (m, 2H), 2.57 - 2.48 (m, 4H), 2.03 (s, 3H). [00756] Example 152: 1-(6-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin- 3-yl)benzyl)-2,6-diazaspiro[3.3]heptan-2-yl)but-2-yn-1-one WSGR Docket No.62619-716.601 [00757] To a solution of Intermediate 5 (100 mg, 293 mmol, HCl salt) and DIEA (109 mg, 845 mmol) in DMF (2.0 mL) were added but-2-ynoic acid (19.5 mg, 232 mmol), EDCI (60.7 mg, 317 mmol) and HOBt (42.8 mg, 317 mmol). The mixture was stirred at 25 °C for 2 hr. The reaction mixture was filtered and the residue was purified by prep-HPLC (column: [water (NH4HCO3) - ACN]; B%: 32% - 62%, 18 min), 1-(6-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H- imidazo[4,5-b]pyridin-3-yl)benzyl)-2,6-diazaspiro[3.3]heptan -2-yl)but-2-yn-1-one (Example 152, 26.4 mg, yield: 22 %) was obtained as a yellow solid. MS: m/z = 540.4 [M + H] ⁺ . ¹ HNMR (400 MHz, Methanol-d4) J = 4.8, 1.6 Hz, 1H), 7.96 - 7.92 (m, 1H), 7.49 - 7.30 (m, 8H), 6.48 (dd, J = 7.6, 4.8 Hz,1H), 4.33 - 4.29 (m, 2H), 4.08 (s, 2H), 3.71 (s, 2H), 3.51 - 3.45 (m, 4H), 2.01 (s, 3H). [00758] Example 153: N-(1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)azetidin-3-yl)but-2-ynamide [00759] DMF was filtered and purified by prep-HPLC (column: [water (NH ₄ HCO ₃ ) - ACN]; B%: 27% - 57%, 18 min), N-(1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin-3- yl)benzyl)azetidin-3-yl)but-2-ynamide (Example 153, 39.9 mg, yield: 33%) was obtained as a yellow solid. MS: m/z = 514.2 [M + H] ⁺ . ¹ HNMR (400 MHz, Methanol-d ₄ ) J = 8.4 Hz, 1H), 8.05 - 8.01 (m, 2H), 7.98 (dd, J = 4.8, 1.6 Hz, 1H), 7.95 (d, J = 8.4 Hz, 1H), 7.52 - 7.45 (m, 4H), 7.44 - 7.37 (m, 3H), 7.31 (dd, J = 7.6, 2.0 Hz, 1H), 6.48 (dd, J = 8.0, 5.2 Hz, 1H), 4.51 - 4.41 (m, 1H), 3.75 (s, 2H), 3.70 - 3.65 (m, 2H), 3.14 - 3.09 (m, 2H), 1.97 (s, 3H). [00760] Example 154: 1-(4-(4-(2-(2-Aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]p yridin- 3-yl)benzyl)piperazin-1-yl)prop-2-yn-1-one WSGR Docket No.62619-716.601 [00761] was stirred at 25 °C for 16 hr. The reaction mixture was diluted with H ₂ O (5 mL) and extracted with EtOAc (10 mL x 3). The combined organic layers were washed with brine (30 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. After purification by prep-TLC (SiO ₂ , CH ₂ Cl ₂ : MeOH = 10 : 1), 1-(4-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5- b]pyridin-3-yl)benzyl)piperazin-1-yl)prop-2-yn-1-one (Example 154, 5.3 mg, yield: 22%) was obtained as a yellow solid. MS: m/z = 514.3 [M + H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ (d, J = 8.4 Hz, 1H), 8.03 (d, J = 7.2 Hz, 2H), 7.98 (dd, J = 5.2, 1.6 Hz, 1H), 7.93 (d, J = 8.8 Hz, 1H), 7.55 - 7.51 (m, 2H), 7.46 - 7.36 (m, 5H), 7.30 (dd, J = 7.6, 1.6 Hz, 1H), 6.47 (dd, J = 7.6, 5.2 Hz, 1H), 3.99 (s, 1H), 3.87 - 3.82 (m, 2H), 3.68 - 3.63 (m, 4H), 2.59 - 2.47 (m, 4H). II. Biological Evaluation Example 1: NanoBRET Target Engagement (TE) Assay [00762] NanoBRET is a highly specific and validated cell-based technique for assessing target engagement (Vasta et al., 2018, Cell Chem Biol.25(2):206-214). The NanoBRET Target Engagement (TE) Intracellular Kinase Assays are based on the NanoBRET System (Promega Corporation), an energy transfer technique designed to measure molecular proximity in living cells. The NanoBRET TE Assays measure the apparent affinity of test compounds by competitive displacement of the NanoBRET tracer compound, which is a cell permeable molecule engineered to be reversibly bound to a NanoLuc® luciferase-kinase fusion expressed in cells. For compound screening, when a test compound binds to the selected kinase, the BRET signal is attenuated. For kinase inhibitors in particular, intracellular target selectivity is fundamental to pharmacological mechanism and allows the proteins of interest to be in the correct cellular confirmation. Although non-cell-based techniques have been developed to measure kinase binding or enzymatic inhibition with accuracy and precision, such approaches can fail to accurately predict engagement of the full-length target protein in the more complex and biologically relevant cellular context (Knight and Shokat, 2005, Chem. Biol.12, 621–637; Smyth and Collins, 2009, J. Chem. Biol.2, 131–151). The NanoBRET assay procedure was used to interrogate the compounds against the full length AKT E17K per manufacturers WSGR Docket No.62619-716.601 suggestions. Briefly, HEK-293 cells (ATCC Cat # CRL-1573) were used for transfection purposes using FuGENE HD Transfection Reagent (Promega Cat # E2311). All cells were evaluated for viability prior to transfection and optimization of the transfection was done prior to experimentation. Greater than 95% viability was used for all experiments. Following transfection, cells were washed and resuspended in Opti-MEM. NanoBRET assays were performed in white, 384-well plates (Corning) at a density of 2x10 ⁵ cells/well. All example compounds were prepared as concentrated stock solutions in DMSO (Sigma-Aldrich). Compounds are dissolved in DMSO to make 10 mM stock solution. Example compounds were transferred as 40uL of 10 mM stock solution to a 384 pp-plate (LABCYTE, PP-0200) and Apricot liquid handler. A Labcyte ECHO 550 compound dispenser was used to facilitate compound transfer directly to cells. Cells were equilibrated for 2 hr with energy transfer probes and example compound prior to BRET measurements. The AKTE17K (Promega Cat # NV2421) as well as specific probe (NanoBRET tracer, Promega Cat # N264B) was prepared at a concentration of 20X in tracer dilution buffer (12.5 mM HEPES, 31.25% PEG-400, pH 7.5). For target engagement analysis, the energy transfer probes were added to the cells at concentrations optimized for the target in question (AKT E17K). Following compound incubation, NanoBRET NanoGlo Substrate (Promega Cat # N157D) and Extracellular Nanoluc Inhibitor (Promega Cat # N235C) was added according to the manufacturer’s recommended protocol, and luminescence was measured on Envision Reader (Perkin Elmer) Multimode Luminometer equipped with 450nmBPfilter (donor)and 600nmLPfilter (acceptor), using 0.5 s integration time. Milli-BRET units (mBU) are calculated by multiplying the raw BRET values by 1000. Apparent tracer affinity values (EC50) were determined using the sigmoidal dose- response (variable slope). Competitive displacement data were then plotted and data were fit to determine the EC50 value for each example compound. Table 2 provides the assay results for select examples. Activity is defined as “+”, for EC ₅₀ greater 600 nanomolar; “++” for EC ₅₀ between 60-600 nanomolar; “+++” for EC50 between 15-60 nanomolar; and “++++”, for EC50 less than 15 nanomolar. Table 2 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 WSGR Docket No.62619-716.601 III. Preparation of Pharmaceutical Dosage Forms [00763] Example 1: Oral capsule [00764] The active ingredient is a compound of Table 1, or a pharmaceutically acceptable salt or solvate thereof. A capsule for oral administration is prepared by mixing 1-1000 mg of active ingredient with starch or other suitable powder blend. The mixture is incorporated into an oral dosage unit such as a hard gelatin capsule, which is suitable for oral administration. [00765] Example 2: Solution for injection [00766] The active ingredient is a compound of Table 1, or a pharmaceutically acceptable salt or solvate thereof, and is formulated as a solution in sesame oil at a concentration of 50 mg- eq/mL. [00767] The examples and embodiments described herein are for illustrative purposes only and various modifications or changes suggested to persons skilled in the art are to be included within the spirit and purview of this application and scope of the appended claims.