Novel heteroaryl derivatives and use thereof in inhibiting AAK1

Abstract

The present invention provides: a novel heteroaryl derivative compound, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof; and a pharmaceutical composition for preventing or treating AAK1 inhibition-related diseases, the composition comprising same as an active ingredient. The heteroaryl derivative compound according to the present invention exhibits excellent inhibitory activity against AAK1, and thus can be effectively used for preventing and treating AAK1 inhibition-related diseases such as acute pain and neuropathic pain.

Description

Novel heteroaryl derivatives and their use for inhibiting AAK1

[0001] This application claims priority to Korean Patent Application No. 10-2024-0057110, filed April 29, 2024, the entire disclosure of which is incorporated herein by reference.

[0002] The present invention relates to novel heteroaryl derivatives, and more particularly, to novel heteroaryl derivatives and their use for inhibiting AAK1.

[0003] Adaptor-associated kinase 1 (AAK1) is a 104 kDa serine / threonine kinase belonging to the Numb-associated kinase (NAK) family, also known as AP2-associated protein kinase 1. It is encoded by the AAK1 gene in humans and is involved in clathrin-mediated endocytosis. AAK1 is a key endocytic kinase known to be expressed in the plasma membrane and cytoplasm and to have two physiological substrates.

[0004] AAK1 has been proposed as a drug target for the treatment of various neurological and psychiatric disorders, including schizophrenia, cognitive deficits in schizophrenia, Parkinson's disease, bipolar disorder, Alzheimer's disease, and neuropathic pain. Recently, AAK1 has been identified as a cellular factor essential for viral replication, making it a potential host target for the development of broad-spectrum antiviral agents.

[0005] Accordingly, various disease treatments targeting AAK1 are being developed, and WO 2017 / 059085 A1, for example, discloses a biaryl kinase inhibitor for the treatment of pain, Alzheimer's disease, Parkinson's disease, and schizophrenia.

[0006] Thus, the promising potential of AAK1 as a drug target for treating neuropathic pain has stimulated the search for AAK1 inhibitors. However, the number of companies developing drugs in this area is limited, necessitating further research on this target.

[0007] The problem to be solved by the present invention is to provide a novel heteroaryl derivative having a structure that exhibits excellent inhibitory activity against AAK1.

[0008] In addition, the problem to be solved by the present invention is to provide a pharmaceutical composition for preventing or treating a disease related to AAK1 inhibition, which comprises a heteroaryl derivative having the novel structure.

[0009] In addition, the problem to be solved by the present invention is to provide a method for preventing or treating a disease related to AAK1 inhibition, which comprises administering a therapeutically effective amount of a heteroaryl derivative having the novel structure to a subject in need thereof.

[0010] In addition, the problem to be solved by the present invention is to provide a use of the novel heteroaryl derivative as an effective ingredient in the manufacture of a pharmaceutical for preventing or treating a disease related to AAK1 inhibition.

[0011] The problems to be solved by the present invention are not limited to the problems mentioned above, and other technical problems not mentioned can be clearly understood by a person having ordinary skill in the technical field to which the present invention belongs from the description below.

[0012] In order to achieve the above-mentioned problem, according to one aspect of the present invention, a heteroaryl derivative compound represented by the following chemical formula 1, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof is provided.

[0013] <Chemical Formula 1>

[0014]

[0015] In the above formula,

[0016] A is CH or N,

[0017] B1, B3, B4 and B5 are C, CH, N or NH,

[0018] B2 is C, CH, N, NH or O,

[0019] The B ring is a 5-membered aromatic heterocycle containing 1 to 4 heteroatoms selected from N and O,

[0020] Y is NH, NR 6 or O,

[0021] R 2 is H or halogen,

[0022] R 4 is H, C 1-4 Alkyl, halogen or C 1-4 It is haloalkyl,

[0023] R 5 is C 1-9 C as straight or branched chain alkyl 3-5 With or without cycloalkyl; or R 6 Connected with, R 5 and R 6 Forming a 5- to 7-membered non-aromatic heterocycle containing N linked to and additionally containing N or O,

[0024] The above R 5 is singular or plural R 5a Is replaced or not replaced,

[0025] The above R 5a is C 1-4 alkyl, amino or hydroxy,

[0026] R 6 is R 5 Connected with, R 5 and R 6 Forming a 5- to 7-membered non-aromatic heterocycle containing N linked to and additionally containing N or O,

[0027] The above B1 is R b1 Is not replaced or substituted with,

[0028] The above R b1 Silver C 1-4 Alkyl or; R b2 Connected to form a C ring containing 0 to 2 N and fused with a B ring,

[0029] The above B2 is R b2 Is replaced or not replaced,

[0030] The above R b2 is R b1 linked to form a C ring fused with a B ring containing 0 to 2 N,

[0031] The above B4 is R b4 Is replaced or not replaced,

[0032] The above R b4 is C 1-4 Alkyl or halogen,

[0033] The fused ring of the above B ring and C ring is a fused ring of two rings containing 1 to 4 N, R f Is replaced or not replaced,

[0034] The above R f is halogen, C 1-4 Haloalkyl or C 1-4 It is alkoxy.

[0035] According to another aspect of the present invention, a pharmaceutical composition for preventing or treating a disease related to AAK1 inhibition is provided, comprising a heteroaryl derivative compound represented by the above chemical formula 1, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.

[0036] According to another aspect of the present invention, a method for preventing or treating a disease associated with AAK1 inhibition is provided, comprising administering a therapeutically effective amount of a heteroaryl derivative compound represented by the above chemical formula 1, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof to a subject in need thereof.

[0037] According to another aspect of the present invention, there is provided a use of a heteroaryl derivative compound represented by the above chemical formula 1, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof as an effective ingredient in the manufacture of a medicament for preventing or treating a disease associated with AAK1 inhibition.

[0038] According to another aspect of the present invention, a pharmaceutical composition comprising a heteroaryl derivative compound represented by the above chemical formula 1, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable additive is provided.

[0039] It was confirmed that the heteroaryl derivative compound of the present invention exhibits excellent inhibitory activity against AAK1, and thus it was revealed that it can be used for the prevention and treatment of diseases related to AAK1 inhibition.

[0040] Therefore, the heteroaryl derivative compound of the present invention can be usefully used in the fields of medicine and pharmacy for the prevention and treatment of acute and chronic pain and neuropathic pain, which are diseases related to AAK1 inhibition.

[0041] The effects of the present invention are not limited to the effects described above, and should be understood to include all effects that can be inferred from the composition of the invention described in the description or claims of the present invention.

[0042] In this specification, AAK1 refers to Adapter-associated kinase 1 (AAK1), a 104 kDa serine / threonine kinase belonging to the Numb-associated kinase (NAK) family, also referred to as AP2-associated protein kinase 1, which is encoded by the AAK1 gene in humans and is an enzyme involved in clathrin-mediated endocytosis.

[0043] The present invention provides a heteroaryl derivative compound represented by the following chemical formula 1, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof.

[0044] <Chemical Formula 1>

[0045]

[0046] In the above formula,

[0047] A is CH or N,

[0048] B1, B3, B4 and B5 are C, CH, N or NH,

[0049] B2 is C, CH, N, NH or O,

[0050] The B ring is a 5-membered aromatic heterocycle containing 1 to 4 heteroatoms selected from N and O,

[0051] Y is NH, NR 6 or O,

[0052] R 2 is H or halogen,

[0053] R 4 is H, C 1-4 Alkyl, halogen or C 1-4 It is haloalkyl,

[0054] R 5 is C 1-9 C as straight or branched chain alkyl 3-5 With or without cycloalkyl; or R 6Connected with, R 5 and R 6 Forming a 5- to 7-membered non-aromatic heterocycle containing N linked to and additionally containing N or O,

[0055] The above R 5 is singular or plural R 5a Is replaced or not replaced,

[0056] The above R 5a is C 1-4 alkyl, amino or hydroxy,

[0057] R 6 is R 5 Connected with, R 5 and R 6 Forming a 5- to 7-membered non-aromatic heterocycle containing N linked to and additionally containing N or O,

[0058] The above B1 is R b1 Is not replaced or substituted with,

[0059] The above R b1 Silver C 1-4 Alkyl or; R b2 Connected to form a C ring containing 0 to 2 N and fused with a B ring,

[0060] The above B2 is R b2 Is replaced or not replaced,

[0061] The above R b2 is R b1 linked to form a C ring fused with a B ring containing 0 to 2 N,

[0062] The above B4 is R b4 Is replaced or not replaced,

[0063] The above R b4 is C 1-4 Alkyl or halogen,

[0064] The fused ring of the above B ring and C ring is a fused ring of two rings containing 1 to 4 N, R fIs replaced or not replaced,

[0065] The above R f is halogen, C 1-4 Haloalkyl or C 1-4 It is alkoxy.

[0066] In one embodiment, the B ring can be pyrrolyl, pyrazolyl, imidazolyl, isoxazolyl, or triazolyl.

[0067] In one embodiment, the R 2 can be H, fluoro or chloro.

[0068] In one embodiment, the R 4 can be H, methyl, fluoro, chloro, difluoromethyl or trifluoromethyl.

[0069] In one embodiment, the R 5 may be ethyl, 2-methyl-propyl-, 4-methyl-pentyl-, 2,4-dimethylpentyl-, cyclopropyl-methyl- or cyclobutyl-methyl-.

[0070] In one embodiment, the R 5 and R 6 The non-aromatic heterocycle formed by linking may be piperazinyl or morpholino.

[0071] In one embodiment, the R 5a can be methyl, amino or hydroxy.

[0072] In one embodiment, the R b1 can be methyl.

[0073] In one embodiment, the fused ring of the B ring and the C ring may be any one selected from the group consisting of the following chemical formulas:

[0074]

[0075] In one embodiment, the R b4 can be methyl or fluoro.

[0076] In one embodiment, the R fmay be fluoro, chloro, trifluoromethyl or methoxy.

[0077] Specific examples of heteroaryl derivative compounds according to the present invention are as follows:

[0078] [1] (S)-1-((6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[0079] [2] (S)-1-((6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[0080] [3] (S)-1-((6-(1H-pyrrolo[3,2-c]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[0081] [4] (S)-1-((6-(1H-pyrrolo[2,3-c]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[0082] [5] (S)-1-((6-(7-fluoroimidazo[1,2-a]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[0083] [6] (S)-1-((6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[0084] [7] (S)-1-((6-(1H-pyrrol-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[0085] [8] (S)-1-((6-(2H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[0086] [9] (S)-1-((6-(3,5-dimethyl-1H-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[0087]

[0010] (S)-1-((6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[0088]

[0011] (S)-1-((6-(6-fluoro-1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[0089]

[0012] (S)-1-((6-(6-chloro-1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[0090]

[0013] (S)-1-((2-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[0091]

[0014] (S)-1-((2-(difluoromethyl)-6-(isoxazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[0092]

[0015] (S)-1-((2-(difluoromethyl)-6-(1H-imidazol-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[0093]

[0016] (S)-1-((2-(difluoromethyl)-6-(3-fluoro-1H-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[0094]

[0017] (S)-1-((2-(difluoromethyl)-6-(1H-imidazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[0095]

[0018] (S)-1-((2-(difluoromethyl)-6-(1H-pyrrol-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[0096]

[0019] (S)-1-((2-(difluoromethyl)-6-(1H-pyrazol-5-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[0097]

[0020] (S)-1-((2-(difluoromethyl)-6-(2H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[0098]

[0021] (S)-1-((2-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[0099]

[0022] (S)-1-(2-(difluoromethyl)-4-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2,4-dimethylpentan-2-amine,

[0100]

[0023] (S)-1-((2-(difluoromethyl)-6-(5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[0101]

[0024] (S)-1-((2-(difluoromethyl)-6-(4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[0102]

[0025] ((S)-1-((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[0103]

[0026] (S)-1-((6-(5-chloro-1H-pyrazolo[3,4-b]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[0104]

[0027] (S)-1-((2-(difluoromethyl)-6-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[0105]

[0028] (S)-1-((2-(difluoromethyl)-6-(6-fluoro-1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[0106]

[0029] (S)-1-((2-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[0107]

[0030] (S)-1-((4-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[0108]

[0031] (S)-1-((4-(difluoromethyl)-6-(2H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[0109]

[0032] ((S)-1-((4-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[0110]

[0033] (S)-1-((5-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[0111]

[0034] (S)-1-((6-(1H-pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[0112]

[0035] (S)-1-((6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[0113]

[0036] (S)-1-((5-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine,

[0114]

[0037] (S)-1-((3-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine,

[0115]

[0038] (S)-1-((4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine,

[0116]

[0039] (S)-1-((6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine,

[0117]

[0040] (S)-1-((4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[0118]

[0041] (S)-1-((5-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[0119]

[0042] (S)-1-((3-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-4-yl)oxy)-2,4-dimethylpentan-2-amine,

[0120]

[0043] (S)-1-((2-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-4-yl)oxy)-2,4-dimethylpentan-2-amine,

[0121]

[0044] (S)-1-((2-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[0122]

[0045] 1-((2-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine,

[0123]

[0046] 1-((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine,

[0124]

[0047] 1-((2-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine,

[0125]

[0048] 1-((2-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine,

[0126]

[0049] 1-((6-(1H-pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine,

[0127]

[0050] 1-((6-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine,

[0128]

[0051] 2-((6-(5-chloro-1H-pyrazolo[3,4-b]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-ol,

[0129]

[0052] 2-((6-(5-chloro-1H-pyrazolo[3,4-b]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-amine,

[0130]

[0053] (S)-1-((4-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine,

[0131]

[0054] (S)-1-((5-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[0132]

[0055] (S)-1-((5-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine,

[0133]

[0056] (S)-1-(4-(1H-pyrrolo[3,2-b]pyridin-1-yl)phenoxy)-2,4-dimethylpentan-2-amine,

[0134]

[0057] (S)-1-((2-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine,

[0135]

[0058] (S)-1-((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine,

[0136]

[0059] (S)-1-((2-(difluoromethyl)-6-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine,

[0137]

[0060] (S)-1-((2-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine,

[0138]

[0061] 1-((4-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine,

[0139]

[0062] 1-((4-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine,

[0140]

[0063] 1-((5-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine,

[0141]

[0064] 1-((5-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine,

[0142]

[0065] 1-(((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine,

[0143]

[0066] 1-(((2-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine,

[0144]

[0067] 1-(((2-(difluoromethyl)-6-(2H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine,

[0145]

[0068] 1-(((2-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine,

[0146]

[0069] 1-(((2-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine,

[0147]

[0070] 1-(((6-(1H-pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine,

[0148]

[0071] 1-((5-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine,

[0149]

[0072] 1-(((5-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine,

[0150]

[0073] 1-(((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine,

[0151]

[0074] 1-(((2-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine,

[0152]

[0075] 1-(((2-(difluoromethyl)-6-(2H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine,

[0153]

[0076] 1-(((2-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine,

[0154]

[0077] 1-(((6-(1H-pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine,

[0155]

[0078] 1-(((6-(2H-1,2,3-triazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine,

[0156]

[0079] 1-((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-ol,

[0157]

[0080] 1-((2-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2-methylpropan-2-ol,

[0158]

[0081] (S)-1-(4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2,4-dimethylpentan-2-amine,

[0159]

[0082] (S)-1-((6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine,

[0160]

[0083] (S)-1-((6-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine,

[0161]

[0084] (S)-1-((6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine,

[0162]

[0085] (S)-1-((6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine,

[0163]

[0086] (S)-1-((6-(4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine,

[0164]

[0087] (S)-1-((6-(6-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine,

[0165]

[0088] (S)-1-((6-(6-fluoro-1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine,

[0166]

[0089] (S)-1-((6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine,

[0167]

[0090] (S)-1-((6-(1H-pyrrolo[2,3-c]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine,

[0168]

[0091] (S)-1-((6-(1H-pyrrolo[2,3-b]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine,

[0169]

[0092] (S)-1-((6-(1H-pyrrolo[3,2-c]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine,

[0170]

[0093] (S)-1-(4-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-4-methylpentan-2-amine,

[0171]

[0094] (S)-1-(4-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(trifluoromethyl)phenoxy)-4-methylpentan-2-amine,

[0172]

[0095] 1-(((6-(2H-1,2,3-triazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine,

[0173]

[0096] 1-(((6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine,

[0174]

[0097] 1-(((6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine,

[0175]

[0098] 1-(((6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine,

[0176]

[0099] 1-(((2-fluoro-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine,

[0177]

[0100] 1-(((2-fluoro-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine,

[0178]

[0101] 1-(((2-fluoro-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine,

[0179]

[0102] 1-(((4-fluoro-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine,

[0180]

[0103] 1-(((4-fluoro-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine,

[0181]

[0104] 1-(((5-fluoro-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine,

[0182]

[0105] 1-(((5-fluoro-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine,

[0183]

[0106] 1-(((6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine,

[0184]

[0107] 1-(2-(difluoromethyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine,

[0185]

[0108] N 1 -(2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)-2-methylpropane-1,2-diamine,

[0186]

[0109] N 1 -(2-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)-2-methylpropane-1,2-diamine,

[0187]

[0110] N 1 -(6-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(trifluoromethyl)pyridin-3-yl)-2-methylpropane-1,2-diamine,

[0188]

[0111] N 1 -(2-(difluoromethyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenyl)-2-methylpropane-1,2-diamine,

[0189]

[0112] N-((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-amine,

[0190]

[0113] N-((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-amine,

[0191]

[0114] N-((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-amine,

[0192]

[0115] N-((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-amine,

[0193]

[0116] N-((1-aminocyclopropyl)methyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-amine,

[0194]

[0117] N-((1-aminocyclopropyl)methyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-amine,

[0195]

[0118] N-((1-aminocyclopropyl)methyl)-4-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-amine,

[0196]

[0119] N-((1-aminocyclopropyl)methyl)-5-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-amine,

[0197]

[0120] 1-((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)amino)-2-methylpropan-2-ol,

[0198]

[0121] 1-((2-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)amino)-2-methylpropan-2-ol,

[0199]

[0122] 1-(2-chloro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine,

[0200]

[0123] 1-(2-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine,

[0201]

[0124] 1-(2,5-dichloro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine,

[0202]

[0125] 2-methyl-1-(2-methyl-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)propan-2-amine,

[0203]

[0126] 1-(2,6-difluoro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine,

[0204]

[0127] 1-(2,5-difluoro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine,

[0205]

[0128] 5-fluoro-3-(4-(piperazin-1-yl)phenyl)-1H-pyrrolo[2,3-b]pyridine,

[0206]

[0129] 5-Fluoro-3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrrolo[2,3-b]pyridine,

[0207]

[0130] 4-(4-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)phenyl)morpholine,

[0208]

[0131] 5-Fluoro-3-(5-(piperazin-1-yl)pyridin-2-yl)-1H-pyrrolo[2,3-b]pyridine,

[0209]

[0132] 5-Fluoro-3-(5-(4-methylpiperazin-1-yl)pyridin-2-yl)-1H-pyrrolo[2,3-b]pyridine,

[0210]

[0133] 4-(6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)morpholine,

[0211]

[0134] 4-(2-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)morpholine,

[0212]

[0135] 4-(2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)-2,2-dimethylmorpholine, and

[0213]

[0136] 3-(6-(difluoromethyl)-5-(3,3-dimethylpiperazin-1-yl)pyridin-2-yl)-1H-pyrrolo[2,3-b]pyridine.

[0214] In defining the compound of formula 1 throughout this specification, the following definitions apply unless otherwise stated.

[0215] The term "alkyl" as used herein refers to a straight-chain or branched-chain saturated hydrocarbon, C 1-10　 Alkyl is preferred. For example, the alkyl includes, but is not limited to, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, tert-butyl, n-pentyl, iso-pentyl, n-hexyl, 3-methylhexyl, 2,2-dimethylpentyl, 2,3-dimethylpentyl, n-heptyl, n-octyl, n-nonyl, and n-decyl.

[0216] The term "cycloalkyl" as used herein means a partially or fully saturated single or fused cyclic hydrocarbon, C 3-10 Refers to a monocyclic, bicyclic or tricyclic functional group. Examples of monocyclic functional groups among cycloalkyls include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexynyl, etc. Bicyclic functional groups among cycloalkyls include bicycloalkyl and spiro functional groups.

[0217] As used herein, the term "hydroxy" or "hydroxy" is defined as -OH, and the term "alkoxy", unless otherwise defined, means alkyloxy, a radical in which the hydrogen atoms of the hydroxy group are replaced by 1 to 10 alkyl groups.

[0218] The term “halogen” or “halo” as used herein means fluorine (F), chlorine (Cl), bromine (Br), or iodine (I).

[0219] The terms “haloalkyl” and “haloalkoxy” as used herein mean alkyl or alkoxy substituted with one or more halogen atoms.

[0220] The term “heteroatom” as used herein means N, O or S.

[0221] The term "aryl" as used herein means an aromatic hydrocarbon, including a polycyclic aromatic ring system in which a carbocyclic aromatic ring or a heteroaryl ring is fused with one or more other rings. Preferably, C 5-12 Aryl, more preferably C 5-10 Aryl. Examples of aryl include, but are not limited to, phenyl, naphthyl, tetrahydronaphthyl, etc.

[0222] The term "heteroaryl" or "aromatic heterocycle" as used herein refers to a heterocyclic ring containing one or more heteroatoms selected from N, O and S as a reducing agent, and benzo or C 3-8It refers to a 3 to 12 membered, more preferably 5 to 10 membered aromatic hydrocarbon group forming a single or fused ring that can be fused with a cycloalkyl. For example, the heteroaryl includes, but is not limited to, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrazinyl, pyrimidyl, pyridazinyl, triazinyl, oxadiazolyl, isoxadiazolyl, tetrazolyl, indolyl, indazolyl, isoxazolyl, oxazolyl, thiazolyl, isothiazolyl, furanyl, benzofuranyl, thiophenyl, benzothiophenyl, benzothiazolyl, benzoxazolyl, benzimidazolyl, quinolinyl, isoquinolinyl, etc.

[0223] The term “heterocycle” or “heterocycloalkyl” as used herein refers to a non-aromatic alkyl ring, which is a non-aromatic carbocyclic ring containing one or more heteroatoms, such as N, O or S, within the ring. The ring may be 5, 6, 7 or 8-membered and / or may be fused to another ring, such as a cycloalkyl or aromatic ring. Examples of such compounds include pyrrolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, imidazolidinyl, pyrazolidinyl, oxazolidinyl, isooxazolidinyl, thiazolidinyl, isothiazolidinyl, dioxolanyl, oxathiolanyl, dithiolanyl, piperidinyl, tetrahydropyranyl, thianyl, piperazinyl, morpholino, and dioxanyl.

[0224] The compound represented by the above chemical formula 1 according to the present invention can be prepared and used in the form of a prodrug, a hydrate, a solvate, and a pharmaceutically acceptable salt to promote absorption in the body or increase solubility, and therefore the above prodrug, hydrate, solvate, and pharmaceutically acceptable salt also fall within the scope of the present invention. In addition, the compound represented by the above chemical formula 1 has a chiral carbon, and thus its stereoisomers exist, and such stereoisomers are also included within the scope of the present invention.

[0225] The term "prodrug," as used herein, refers to a substance that is transformed into the parent drug in vivo. Prodrugs are often used because, in some cases, they are easier to administer than the parent drug. For example, they may be bioactive by oral administration, whereas the parent drug may not be. Prodrugs may also have improved solubility in pharmaceutical compositions compared to the parent drug. For example, prodrugs may be biohydrolyzable esters of compounds according to the present invention and pharmaceutically acceptable salts thereof. Another example of a prodrug may be a short peptide (polyamino acid) linked to an acid group that is metabolized to reveal the active site of the peptide.

[0226] The term "hydrate" as used herein means a compound of the present invention or a salt thereof containing a stoichiometric or non-stoichiometric amount of water bound by non-covalent intermolecular forces.

[0227] The term "solvate" as used herein refers to a compound of the present invention or a salt thereof that contains a stoichiometric or non-stoichiometric amount of a solvent bound by non-covalent intermolecular forces. Preferred solvents include those that are volatile, non-toxic, and / or suitable for human administration.

[0228] The term "isomer" as used herein refers to a compound of the present invention or a salt thereof that has the same chemical formula or molecular formula but is structurally or sterically different. Such isomers include structural isomers such as tautomers, and stereoisomers such as R or S isomers having an asymmetric carbon center, geometric isomers (trans, cis), and diastereomers. All of these isomers and mixtures thereof are also included in the scope of the present invention. In particular, when the compound of formula 1 has optical isomers, stereoisomers, regioisomers, or rotamers, these are also included in the compound of formula 1, and can be obtained as a single product according to synthetic and separation methods known in the art. For example, when the compound of formula 1 includes optical isomers, optical isomers resolved from this compound are also included in the compound of formula 1. Optical isomers can be prepared by methods known per se.

[0229] The term "pharmaceutically acceptable salt" as used herein means a salt form of a compound that does not cause serious irritation to an organism to which the compound is administered and does not impair the biological activity and physical properties of the compound. The pharmaceutical salt includes acid addition salts formed by acids that form non-toxic acid addition salts containing pharmaceutically acceptable anions, for example, inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrobromic acid, and hydroiodic acid; organic carboxylic acids such as tartaric acid, formic acid, citric acid, acetic acid, trichloroacetic acid, trifluoroacetic acid, gluconic acid, benzoic acid, lactic acid, fumaric acid, maleic acid, and salicylic acid; and sulfonic acids such as methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid. For example, pharmaceutically acceptable carboxylic acid salts include metal salts or alkaline earth metal salts formed by lithium, sodium, potassium, calcium, magnesium, etc.; amino acid salts such as lysine, arginine, guanidine, etc.; organic salts such as dicyclohexylamine, N-methyl-D-glucamine, tris(hydroxymethyl)methylamine, diethanolamine, choline, and triethylamine, etc. The compound of formula 1 according to the present invention can be converted into its salt by a conventional method.

[0230] The present invention also provides a method for preparing a compound of the above chemical formula 1. The synthetic methods of Examples 1 to 136 are exemplified as a method for preparing a compound of the chemical formula 1 of the present invention, and the synthetic methods of Examples 1 to 136 do not limit the method for preparing a compound of the chemical formula 1 according to the present invention. The synthetic methods of Examples 1 to 136 are merely examples, and it is obvious that they can be easily modified by those skilled in the art depending on specific substituents.

[0231] The present invention also provides a pharmaceutical composition for preventing or treating a disease related to AAK1 inhibition, comprising a heteroaryl derivative compound represented by the above chemical formula 1, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.

[0232] The present invention also provides a method for preventing or treating a disease associated with AAK1 inhibition, comprising administering a therapeutically effective amount of a heteroaryl derivative compound represented by the above chemical formula 1, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof to a subject in need thereof.

[0233] The present invention also provides the use of a heteroaryl derivative compound represented by the above chemical formula 1, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof as an effective ingredient in the manufacture of a medicine for preventing or treating a disease associated with AAK1 inhibition.

[0234] AAK1 inhibitory activity (IC) of the heteroaryl derivative compound of the present invention 50 ) was measured, it was confirmed that it exhibited excellent inhibitory activity against AAK1, and it was revealed that it can be used for the prevention and treatment of diseases related to AAK1 inhibition.

[0235] In one embodiment, the disease associated with AAK1 inhibition may be selected from the group consisting of acute pain, chronic pain, inflammatory pain, neuropathic pain, Parkinson's disease, Alzheimer's disease, schizophrenia, bipolar disorder, muscular dystrophy, and viral infection diseases. Accordingly, the heteroaryl derivative compound of the present invention can be used as a broad-spectrum antiviral agent.

[0236] The present invention also provides a pharmaceutical composition comprising a heteroaryl derivative compound represented by the above chemical formula 1, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable additive.

[0237] The above additives may include pharmaceutically acceptable carriers such as excipients, disintegrants, sweeteners, lubricants or flavoring agents that are commonly used, and may be formulated into oral preparations such as tablets, capsules, powders, granules and suspensions, emulsions or syrups according to a conventional method; or parenteral preparations such as external solutions, external suspensions, external emulsions, gels (ointments, etc.), inhalants, sprays and injections. The above preparations may be formulated into various forms, for example, single-dose or multiple-dose dosage forms.

[0238] The subject to which the pharmaceutical composition of the present invention is administered may be, for example, a human, a monkey, a cow, a horse, a sheep, a pig, a chicken, a turkey, a cat, a dog, a mouse, a rat, a rabbit, or a guinea pig, and may be, for example, a mammal, for example, a human, but is not limited thereto.

[0239] In addition, the pharmaceutical composition of the present invention can be administered orally or parenterally, and in case of parenteral administration, it can be administered by routes such as skin, transdermally, ocularly, intraperitoneally, rectal, or intravenously, intramuscularly, subcutaneously, intrauterinely, intracerebroventricularly, or topical administration. Topical ocular administration includes, for example, direct intraocular administration, or administration around the eye, behind the eye, subretinal, central retinal, extrafoveal, subconjunctival, intravitreous, intracameral, or suprachoroidal. The pharmaceutical composition can be administered through an insertion device.

[0240] The dosage of the active ingredient contained in the pharmaceutical composition of the present invention varies depending on the patient's condition and weight, the degree of the disease, the form of the active ingredient, the route and period of administration, and can be appropriately adjusted depending on the patient. For example, the active ingredient may be administered at a dosage of 0.0001 to 1000 mg / kg per day, preferably 0.001 to 100 mg / kg, and the administration may be administered once a day or divided into several times. In addition, the pharmaceutical composition of the present invention may contain the active ingredient at a weight percentage of 0.001 to 90% based on the total weight of the composition.

[0241]

[0242] Hereinafter, the present invention will be described in more detail through examples and experimental examples. However, the following examples and experimental examples are intended to illustrate the present invention and are not intended to limit the scope of the present invention.

[0243]

[0244] <Common Reaction Formula I>

[0245]

[0246] In the following examples, proton NMR spectra were recorded on a Bruker 500 MHz NMR spectrometer. Chemical shifts were reported as δ values. Liquid chromatography-mass spectrometry (LC-MS) was performed on a Waters ACQUITY UPLC H-Class coupled to an ACQUITY QDa detector.

[0247]

[0248] Example 1: (S)-1-((6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

[0249]

[0250] Part A: (S)-1-((6-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0251]

[0252] To a solution of (S)-2-amino-2,4-dimethylpentan-1-ol (1.6 g, 6.25 mmol) in tetrahydrofuran (20 mL) was added potassium tert-butoxide (2.5 g, 8.52 mmol) at room temperature. After 3 min, a portion of 2-bromo-5-fluoropyridine (1.0 g, 5.68 mmol) was added, and the reaction mixture was stirred at room temperature. The reaction progress was monitored by TLC and HPLC. After the reaction was completed, water was added to quench the reaction and diluted with EtOAc. The separated organic layer was washed with water and brine, dried over magnesium sulfate, and concentrated. The residue was purified by MPLC (silica gel, CH2Cl2: MeOH = 10:1, v / v) to give a pale-yellow liquid (0.90 g, 55.1%). LC-MS (ESI+) m / z287.3 [(M+H) + , calcd. C 12 H 19 BrN2Om / z286.0].

[0253]

[0254] Part B: (S)-1-((6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0255]

[0256] A solution of (S)-1-((6-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 1, Part A), tert-butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (189.1 mg, 0.52 mmol), tetrakis(triphenylphosphine)palladium(0) (40.2 mg, 0.03 mmol), and potassium carbonate (192.4 mg, 1.39 mmol) in 1,4-dioxane (8 mL) and water (2 mL) was irradiated in a microwave at 130 °C for 1 h. The progress of the reaction was monitored by TLC and HPLC. After the reaction was completed, the mixture was diluted with EtOAc and water. The separated organic layer was washed with water and brine, dried over magnesium sulfate, and concentrated. The residue was purified with PLC (silica gel, eluted with CH2Cl2: MeOH = 9:1, v / v). The required spot was collected, dissolved in 5% methanol dichloromethane (20 mL), filtered, and concentrated under reduced pressure to obtain an ivory-colored powder (34.3 mg, 28.7%). 1 H NMR (500 MHz, MeOD) δ8.56 (s, 1H), 8.30-8.39 (m, 5H), 4.36-4.44 (m, 2H), 1.83-1.93 (m, 2H), 1.71-1.75 (m, 1H), 1.54 (s, 3H), 1.07 (d, 3H), 1.04 (d, 3H). LC-MS (ESI+)m / z343.2 [(M+H) + , calcd. C 19 H 23 FN4Om / z342.1].

[0257]

[0258] Example 2: (S)-1-((6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

[0259]

[0260] Example 2 was prepared according to a similar procedure as described for Example 1.

[0261] Part B: (S)-1-((6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0262]

[0263] This compound was prepared using (S)-1-((6-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 1, Part A) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (179.7 mg, 0.52 mmol) to obtain an ivory powder (34.3 mg, 30.3%). 1 H NMR (500 MHz, MeOD) δ8.61-8.62 (m, 1H), 8.34 (d, 1H), 8.22-8.23 (m, 1H), 7.87 (s, 1H), 7.74 (d, 1H), 7.46-7.48 (m, 1H), 7.17-7.20 (m, 1H), 3.89-4.00 (m, 2H), 1.81-1.87 (m, 1H), 1.62-1.66 (m, 1H), 1.53-1.57 (m, 1H), 1.32 (s, 3H), 1.01 (d, 3H), 0.99 (d, 3H). LC-MS (ESI+) m / z 325.3 [(M+H) + , calcd. C 19 H 24N4Om / z324.1].

[0264]

[0265] Example 3: (S)-1-((6-(1H-pyrrolo[3,2-c]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((6-(1H-pyrrolo[3,2-c]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

[0266]

[0267] Example 3 was prepared according to a similar procedure as described for Example 1.

[0268] Part B: (S)-1-((6-(1H-pyrrolo[3,2-c]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0269]

[0270] This compound was prepared using (S)-1-((6-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 1, Part A) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[3,2-c]pyridine-1-carboxylate (179.7 mg, 0.52 mmol) to obtain a powder (24.3 mg, 21.5%). 1 H NMR (500 MHz, MeOD) δ9.74 (s, 1H), 8.63 (d, 1H), 8.47-8.51 (m, 2H), 8.22 (d, 1H), 8.04-8.09 (m, 2H), 4.29-4.38 (m, 2H), 1.83-1.91 (m, 2H), 1.70-1.74 (m, 1H), 1.52 (s, 3H), 1.06 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+)m / z325.4 [(M+H) + , calcd. C 19 H 24N4Om / z324.1].

[0271]

[0272] Example 4: (S)-1-((6-(1H-pyrrolo[2,3-c]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((6-(1H-pyrrolo[2,3-c]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

[0273]

[0274] Example 4 was prepared according to a similar procedure as described for Example 1.

[0275] Part B: (S)-1-((6-(1H-pyrrolo[2,3-c]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0276]

[0277] This compound was prepared using (S)-1-((6-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 1, Part A) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (179.7 mg, 0.52 mmol) to obtain a pale- powder (30.90 mg, 27.3%). 1 H NMR (500 MHz, MeOD) δ8.89 (s, 1H), 8.55 (d, 1H), 8.13-8.17 (m, 2H), 8.04 (d, 1H), 7.63 (d, 1H), 7.41 (s, 1H), 4.17-4.27 (m, 2H), 1.78-1.85 (m, 2H), 1.65-1.68 (m, 1H), 1.47 (s, 3H), 1.02 (d, 3H), 0.98 (d, 3H). LC-MS (ESI+)m / z325.4 [(M+H) + , calcd. C 19 H 24N4Om / z324.1].

[0278]

[0279] Example 5: (S)-1-((6-(7-fluoroimidazo[1,2-a]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((6-(7-fluoroimidazo[1,2-a]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

[0280]

[0281] Example 5 was prepared according to a similar procedure as described for Example 1.

[0282] Part B: (S)-1-((6-(7-fluoroimidazo[1,2-a]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0283] This compound was prepared using (S)-1-((6-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (24.0 mg, 0.08 mmol) (Example 1, Part A) and 7-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)imidazo[1,2-a]pyridine (136.9 mg, 0.52 mmol) and an ivory powder (11.4 mg, 39.8%) was obtained. 1 H NMR (500 MHz, MeOD) δ9.85-9.88 (m, 1H), 8.38 (d, 1H), 8.03 (s, 1H), 7.81 (d, 1H), 7.46-7.49 (m, 1H), 7.27-7.29 (m, 1H), 6.94-6.98 (m, 1H), 3.87-3.92 (m, 2H), 1.80-1.85 (m, 1H), 1.48-1.59 (m, 2H), 1.25 (s, 3H), 1.00 (d, 3H), 0.98 (d, 3H). LC-MS (ESI+)m / z343.4 [(M+H) + , calcd. C 19 H 23FN4Om / z342.1].

[0284]

[0285] Example 6: (S)-1-((6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

[0286]

[0287] Example 6 was prepared according to a similar procedure as described for Example 1.

[0288] Part B: (S)-1-((6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0289]

[0290] This compound was prepared using (S)-1-((6-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 1, Part A) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (153.6 mg, 0.52 mmol) to obtain a pale-ivory powder (24.1 mg, 25.2%). 1 H NMR (500 MHz, MeOD) δ8.43-8.48 (m, 3H), 8.28 (d, 2H), 4.23-4.40 (m, 2H), 1.80-1.89 (m, 2H), 1.70-1.73 (m, 1H), 1.51 (s, 3H), 1.06 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+)m / z275.3 [(M+H) + , calcd. C 15 H 22 N4Om / z274.1].

[0291]

[0292] Example 7: (S)-1-((6-(1H-pyrrol-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((6-(1H-pyrrol-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

[0293]

[0294] Example 7 was prepared according to a similar procedure as described for Example 1.

[0295] Part B: (S)-1-((6-(1H-pyrrol-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0296] This compound was prepared using (S)-1-((6-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 1, Part A) and 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole (100.8 mg, 0.52 mmol) to obtain a pale-red liquid (15.8 mg, 16.6%). 1 H NMR (500 MHz, MeOD) δ10.00 (d, 1H), 7.53 (d, 1H), 7.36-7.38 (m, 1H), 7.27 (s, 1H), 6.77 (d, 1H), 6.56 (d, 1H), 3.80-3.86 (m, 2H), 1.78-1.82 (m, 1H), 1.46-1.57 (m, 2H), 1.23 (s, 3H), 0.99 (d, 3H), 0.97 (d, 3H) LC-MS (ESI+)m / z274.5 [(M+H) + , calcd. C 16 H 23 N3Om / z273.1].

[0297]

[0298] Example 8: (S)-1-((6-(2H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((6-(2H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

[0299]

[0300] Example 8 was prepared according to a procedure similar to that described for Example 1.

[0301] Part B: (S)-1-((6-(2H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0302]

[0303] This compound was prepared as an intermediate using (S)-1-((6-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 1, Part A) and 2-(tetrahydro-2H-pyran-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-1,2,3-triazole (145.8 mg, 0.52 mmol). After purification, hydrochloric acid (1.25 M methanol solution, 10 mL) was added and stirred at 80 °C for deprotection of the tetrahydro-2H-pyranyl group. After completion of the reaction, the product was concentrated under reduced pressure. The residue was extracted with EtOAc and 10% NaOH solution (aq.). The separated organic layer was washed with water and brine, dried over magnesium sulfate, and concentrated. The residue was recrystallized from tetrahydrofuran and n-hexane to obtain a pale ivory powder (42.2 mg, 44.0%). 1H NMR (500 MHz, MeOD) δ8.58-8.60 (m, 2H), 8.39-8.40 (m, 1H), 8.21-8.23 (m, 1H), 4.35-4.41 (m, 2H), 1.82-1.90 (m, 2H), 1.73-1.75 (m, 1H), 1.52 (s, 3H), 1.06 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+)m / z276.3 [(M+H) + , calcd. C 14 H 21 N5Om / z275.1].

[0304]

[0305] Example 9: (S)-1-((6-(3,5-dimethyl-1H-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((6-(3,5-dimethyl-1H-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

[0306]

[0307] Example 9 was prepared according to a similar procedure as described for Example 1.

[0308] Part B: (S)-1-((6-(3,5-dimethyl-1H-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0309] This compound was prepared using (S)-1-((6-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 1, Part A) and 3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (116.0 mg, 0.52 mmol) to obtain a pale-ivory powder (15.6 mg, 14.8%). 1H NMR (500 MHz, MeOD) δ8.29 (d, 1H), 7.45-7.47 (m, 1H), 7.34 (d, 1H), 3.84-3.91 (m, 2H), 2.26 (s, 6H), 1.77-1.81 (m, 1H), 1.54-1.58 (m, 1H), 1.47-1.51 (m, 1H), 1.24 (s, 3H), 0.98 (d, 3H), 0.96 (d, 3H). LC-MS (ESI+)m / z303.5 [(M+H) + , calcd. C 17 H 26 N4Om / z302.2].

[0310]

[0311] Example 10: (S)-1-((6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

[0312]

[0313] Potassium triphosphate (147.8 mg, 0.70 mmol) was added to a solution of (S)-1-((6-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 1, Part A), 1H-pyrrolo[3,2-b]pyridine (41.1 mg, 0.35 mmol), copper(II) acetate (6.3 mg, 0.03 mmol), and (2Z)-2-hydroxyimino-1,2-diphenylethanol (7.9 mg, 0.03 mmol) in dimethylsulfoxide (2 mL). The reaction mixture was irradiated in a microwave at 140 °C for 1 h. The progress of the reaction was monitored by TLC and HPLC. After the reaction was completed, the mixture was diluted with EtOAc and water. The separated organic layer was washed with water and brine, dried over magnesium sulfate, and concentrated. The residue was purified by PLC (silica gel, eluted with CH2Cl2: MeOH = 10:1, v / v). The required spot was collected, dissolved in 5% methanol in dichloromethane (20 mL), filtered, and concentrated under reduced pressure to obtain (S)-1-((6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine as an ivory powder (30.8 mg, 27.2%). 1 H NMR (500 MHz, MeOD) δ9.39 (d, 1H), 8.65-8.69 (m, 2H), 8.45 (d, 1H), 7.79-7.86 (m, 3H), 7.12 (d, 1H), 4.20-4.30 (m, 2H), 1.83-1.85 (m, 2H), 1.72-1.73 (m, 1H), 1.51 (s, 3H), 1.06 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+)m / z325.3 [(M+H) + , calcd. C 19 H 24 N4Om / z324.1].

[0314]

[0315] Example 11: (S)-1-((6-(6-fluoro-1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((6-(6-fluoro-1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

[0316]

[0317] Example 11 was prepared according to a similar procedure as described for Example 10 using (S)-1-((6-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 1, Part A), 6-fluoro-1H-pyrrolo[3,2-b]pyridine (47.4 mg, 0.35 mmol) to obtain an ivory powder (25.7 mg, 21.5%). 1 H NMR (500 MHz, MeOD) δ9.39 (d, 1H), 8.65-8.69 (m, 1H), 8.43 (d, 1H), 7.76-7.84 (m, 3H), 7.12 (d, 1H), 4.20-4.30 (m, 2H), 1.83-1.85 (m, 2H), 1.71-1.73 (m, 1H), 1.52 (s, 3H), 1.06 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+)m / z343.5 [(M+H) + , calcd. C 19 H 23 FN4Om / z342.1].

[0318]

[0319] Example 12: (S)-1-((6-(6-chloro-1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((6-(6-chloro-1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

[0320]

[0321] Example 12 was prepared according to a similar procedure as described for Example 10 using (S)-1-((6-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 1, Part A), 6-chloro-1H-pyrrolo[3,2-b]pyridine (53.1 mg, 0.35 mmol) to obtain a pale-brown powder (24.3 mg, 19.4%). 1 H NMR (500 MHz, MeOD) δ9.19 (s, 1H), 8.70 (s, 1H), 8.49 (d, 1H), 8.44 (d, 1H), 7.78-7.81 (m, 2H), 7.01 (d, 1H), 4.19-4.30 (m, 2H), 1.83-1.90 (m, 2H), 1.69-1.73 (m, 1H), 1.52 (s, 3H), 1.08 (d, 3H), 1.04 (d, 3H). LC-MS (ESI+)m / z359.6 [(M+H) + , calcd. C 19 H 23 ClN4Om / z358.1].

[0322]

[0323] Example 13: (S)-1-((2-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((2-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

[0324]

[0325] Part A: 6-Bromo-2-(difluoromethyl)-3-fluoropyridine

[0326]

[0327] A solution was prepared by adding 6-bromo-3-fluoropicolinaldehyde (5.0 g, 24.51 mmol) and CH2Cl2 (100 mL) to a 500 mL round-bottomed flask. After cooling to 20°C, diethylaminosulfur trifluoride (7.1 mL, 49.02 mmol) was added dropwise. The mixture was slowly warmed to room temperature and stirred at room temperature for 1 h. The progress of the reaction was monitored by TLC and HPLC. After completion of the reaction, the mixture was slowly quenched with saturated NaHCO3 solution (aq.) at -10°C. Water (100 mL) was added, and the separated organic layer was washed with water and brine, dried over magnesium sulfate, and concentrated. The residue was purified by MPLC (silica gel, eluted with 0–20% EtOAc in n-hexane) to give 6-bromo-2-(difluoromethyl)-3-fluoropyridine (4.4 g, 80.2%) as an ivory powder. LC-MS (ESI+) m / z 226.3 [(M+H) + , calcd. C6H3BrF3Nm / z224.9].

[0328]

[0329] Part B: (S)-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0330]

[0331] This compound was prepared according to a similar procedure as described for Part A of Example 1 using (S)-2-amino-2,4-dimethylpentan-1-ol (0.639 g, 4.87 mmol) and 6-bromo-2-(difluoromethyl)-3-fluoropyridine (1.0 g, 4.42 mmol) (Example 13, Part A) to obtain a pale-yellow liquid (1.2 g, 85.1%). LC-MS (ESI+) m / z 337.5 [(M+H) + , calcd.m / zC 13 H 19 BrF2N2O 336.0].

[0332]

[0333] Part C: (S)-1-((2-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0334]

[0335] This compound was prepared according to a similar procedure as described for Part B of Example 1 using (S)-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (130.8 mg, 0.44 mmol) to obtain an ivory powder (30.7 mg, 31.9%). 1 H NMR (500 MHz, MeOD) δ8.54 (d, 2H), 7.91 (d, 1H), 7.73 (d, 1H), 7.00-7.21 (m, 1H), 4.18-4.26 (m, 2H), 1.82-1.86 (m, 2H), 1.65-1.70 (m, 1H), 1.49 (s, 3H), 1.03 (d, 3H), 0.97 (d, 3H). LC-MS (ESI+)m / z325.3 [(M+H) + , calcd. C 16 H 22 F2N4Om / z324.1].

[0336]

[0337] Example 14: (S)-1-((2-(difluoromethyl)-6-(isoxazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((2-(difluoromethyl)-6-(isoxazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

[0338]

[0339] Example 14 was prepared according to a similar procedure as described for Example 13.

[0340] Part C: (S)-1-((2-(difluoromethyl)-6-(isoxazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0341]

[0342] This compound was prepared using (S)-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoxazole (86.7 mg, 0.44 mmol) to obtain an ivory powder (20.8 mg, 21.5%). 1 H NMR (500 MHz, MeOD) δ8.47 (d, 2H), 7.88 (d, 1H), 7.71 (d, 1H), 7.00-7.18 (m, 1H), 4.16-4.23 (m, 2H), 1.79-1.72 (m, 2H), 1.67-1.69 (m, 1H), 1.46 (s, 3H), 1.02 (d, 3H), 0.99 (d, 3H). LC-MS (ESI+)m / z326.3 [(M+H) + , calcd. C 16 H 21 F2N3O2m / z325.1].

[0343]

[0344] Example 15: (S)-1-((2-(difluoromethyl)-6-(1H-imidazol-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((2-(difluoromethyl)-6-(1H-imidazol-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

[0345]

[0346] Example 15 was prepared according to a similar procedure as described for Example 10 using (S)-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and 1H-imidazole (20.1 mg, 0.30 mmol) to obtain an ivory powder (13.5 mg, 14.0%). 1 H NMR (500 MHz, MeOD) δ9.04 (s, 1H), 8.05 (s, 1H), 7.89-7.86 (m, 2H), 7.41 (s, 1H), 7.02-7.24 (m, 1H), 4.20-4.28 (m, 2H), 1.79-1.83 (m, 2H), 1.64-1.68 (m, 1H), 1.46 (s, 3H), 1.00 (d, 3H), 0.95 (d, 3H). LC-MS (ESI+)m / z325.3 [(M+H) + , calcd. C 16 H 22 F2N4Om / z324.1].

[0347]

[0348] Example 16: (S)-1-((2-(difluoromethyl)-6-(3-fluoro-1H-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((2-(difluoromethyl)-6-(3-fluoro-1H-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

[0349]

[0350] Example 16 was prepared according to a procedure similar to that described for Example 13.

[0351] Part C: (S)-1-((2-(difluoromethyl)-6-(3-fluoro-1H-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0352]

[0353] This compound was prepared using (S)-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and 3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (94.3 mg, 0.44 mmol) to obtain a pale-brown powder (15.4 mg, 15.9%). 1 H NMR (500 MHz, MeOD) δ8.04 (d, 1H), 7.59 (d, 1H), 6.82-7.04 (m, 1H), 3.93-4.00 (m, 2H), 2.15-2.18 (m, 1H), 2.00-2.02 (m, 1H), 1.79-1.81 (m, 1H), 1.31 (s, 3H), 0.98 (d, 3H), 0.96 (d, 3H). LC-MS (ESI+)m / z343.0 [(M+H) + , calcd. C 16 H 21 F3N4Om / z342.1].

[0354]

[0355] Example 17: (S)-1-((2-(difluoromethyl)-6-(1H-imidazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((2-(difluoromethyl)-6-(1H-imidazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

[0356]

[0357] Example 17 was prepared according to a procedure similar to that described for Example 13.

[0358] Part C: (S)-1-((2-(difluoromethyl)-6-(1H-imidazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0359]

[0360] This compound was prepared using (S)-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-imidazole-1-carboxylate, and a pale-yellow powder (20.3 mg, 21.1%) was obtained. 1 H NMR (500 MHz, MeOD) δ8.13 (s, 1H), 8.04 (s, 1H), 7.81 (d, 1H), 7.03-7.22 (m, 2H), 4.23-4.32 (m, 2H), 1.85-1.87 (m, 2H), 1.69-1.72 (m, 1H), 1.51 (s, 3H), 1.04 (d, 3H), 1.00 (d, 3H). LC-MS (ESI+)m / z325.3 [(M+H) + , calcd. C 16 H 22 F2N4Om / z324.1].

[0361]

[0362] Example 18: (S)-1-((2-(difluoromethyl)-6-(1H-pyrrol-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((2-(difluoromethyl)-6-(1H-pyrrol-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

[0363]

[0364] Example 18 was prepared according to a procedure similar to that described for Example 13.

[0365] Part C: (S)-1-((2-(difluoromethyl)-6-(1H-pyrrol-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0366]

[0367] This compound was prepared using (S)-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole-1-carboxylate (130.4 mg, 0.44 mmol) to obtain a pale-brown powder (15.2 mg, 15.8%). 1 H NMR (500 MHz, MeOD) δ7.62 (d, 1H), 7.47 (d, 1H), 7.31 (s, 1H), 6.77-6.99 (m, 1H), 6.74-6.75 (m, 1H), 6.58 (d, 1H), 3.86-3.93 (m, 2H), 1.78-1.87 (m, 1H), 1.58-1.61 (m, 1H), 1.48-1.52 (m, 1H), 1.29 (s, 3H), 0.98 (d, 3H), 0.95 (d, 3H). LC-MS (ESI+)m / z324.6 [(M+H) + , calcd. C 17 H 23 F2N3Om / z323.1].

[0368]

[0369] Example 19: (S)-1-((2-(difluoromethyl)-6-(1H-pyrazol-5-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((2-(difluoromethyl)-6-(1H-pyrazol-5-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

[0370]

[0371] Example 19 was prepared according to a procedure similar to that described for Example 13.

[0372] Part C: (S)-1-((2-(difluoromethyl)-6-(1H-pyrazol-5-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0373]

[0374] This compound was prepared using (S)-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (130.8 mg, 0.44 mmol) and an ivory powder (25.3 mg, 26.3%) was obtained. 1 H NMR (500 MHz, MeOD) δ8.15 (d, 1H), 8.04 (s, 1H), 7.81 (d, 1H), 7.04-7.25 (m, 2H), 4.23-4.32 (m, 2H), 1.85-1.87 (m, 2H), 1.69-1.72 (m, 1H), 1.51 (s, 3H), 1.04 (d, 3H), 1.00 (d, 3H). LC-MS (ESI+)m / z325.1 [(M+H) + , calcd. C 16 H 22 F2N4Om / z324.1].

[0375]

[0376] Example 20: (S)-1-((2-(difluoromethyl)-6-(2H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((2-(difluoromethyl)-6-(2H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

[0377]

[0378] Example 20 was prepared according to a procedure similar to that described for Example 8.

[0379] Part B: (S)-1-((2-(difluoromethyl)-6-(2H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0380]

[0381] This compound was prepared using (S)-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and 2-(tetrahydro-2H-pyran-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-1,2,3-triazole (124.1 mg, 0.44 mmol) and an ivory powder (30.2 mg, 31.3%) was obtained. 1 H NMR (500 MHz, MeOD) δ8.44-8.48 (m, 1H), 8.17 (d, 1H), 7.80 (d, 1H), 7.03-7.25 (m, 1H), 4.23-4.31 (m, 2H), 1.8-1.88 (m, 2H), 1.69-1.72 (m, 1H), 1.51 (s, 3H), 1.05 (d, 3H), 0.99 (d, 3H). LC-MS (ESI+) m / z 000.0 [(M+H)+, calcd. C 15 H 21 F2N5O m / z 325.1].

[0382]

[0383] Example 21: (S)-1-((2-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((2-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

[0384]

[0385] Example 21 was prepared according to a procedure similar to that described for Example 13.

[0386] Part C: (S)-1-((2-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0387]

[0388] This compound was prepared using (S)-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and tert-butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (161.1 mg, 0.44 mmol) to obtain a pale-yellow powder (28.6 mg, 24.5%). 1 H NMR (500 MHz, MeOD) δ9.06-9.08 (m, 1H), 8.43 (s, 1H), 8.28 (s, 1H), 8.02 (m, 1H), 7.72 (d, 1H), 7.11-7.33 (m, 1H), 4.19-4.28 (m, 2H), 1.83-1.88 (m, 2H), 1.67-1.72 (m, 1H), 1.51 (s, 3H), 1.06 (d, 3H), 1.00 (d, 3H). LC-MS (ESI+)m / z392.4 [(M+H) + , calcd. C 20 H 23 F3N4Om / z392.1].

[0389]

[0390] Example 22: (S)-1-(2-(difluoromethyl)-4-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2,4-dimethylpentan-2-amine [(S)-1-(2-(difluoromethyl)-4-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2,4-dimethylpentan-2-amine]

[0391]

[0392] Example 22 was prepared according to a procedure similar to that described for Example 13.

[0393] Part B: (S)-1-(4-bromo-2-(difluoromethyl)phenoxy)-2,4-dimethylpentan-2-amine

[0394]

[0395] This compound was prepared using (S)-2-amino-4-methylpentan-2-ol (320.7 mg, 2.44 mmol) and 4-bromo-2-(difluoromethyl)-1-fluorobenzene (500.0 mg, 2.22 mmol) and a pale-yellow liquid (580.3 mg, 77.6%) was obtained. LC-MS (ESI+) m / z 336.6 [(M+H) + , calcd. C 14 H 20 BrF2NOm / z335.0].

[0396]

[0397] Part C: (S)-1-(2-(difluoromethyl)-4-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2,4-dimethylpentan-2-amine

[0398]

[0399] This compound was prepared using (S)-1-(4-bromo-2-(difluoromethyl)phenoxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 22, Part B) and tert-butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (161.5 mg, 0.45 mmol) to obtain an ivory powder (30.2 mg, 25.9%). 1H NMR (500 MHz, MeOD) δ9.04-9.07 (m, 1H), 8.44 (s, 1H), 8.28 (s, 1H), 8.03 (m, 1H), 7.74 (d, 1H), 7.12-7.33 (m, 2H), 4.19-4.28 (m, 2H), 1.83-1.88 (m, 2H), 1.67-1.72 (m, 1H), 1.51 (s, 3H), 1.06 (d, 3H), 1.00 (d, 3H). LC-MS (ESI+)m / z392.6 [(M+H) + , calcd. C 21 H 24 F3N3Om / z391.1].

[0400]

[0401] Example 23: (S)-1-((2-(difluoromethyl)-6-(5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((2-(difluoromethyl)-6-(5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

[0402]

[0403] Example 23 was prepared according to a procedure similar to that described for Example 13.

[0404] Part C: (S)-1-((2-(difluoromethyl)-6-(5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0405]

[0406] This compound was prepared using (S)-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (183.3 mg, 0.44 mmol) to obtain a pale-yellow powder (35.4 mg, 26.9%). 1 H NMR (500 MHz, MeOD) δ9.21 (s, 1H), 9.08-9.10 (m, 1H), 8.28-8.29 (m, 1H), 8.19 (s, 1H), 7.85-7.87 (m, 1H), 7.10-7.31 (m, 1H), 4.26-4.34 (m, 2H), 1.86-1.90 (m, 2H), 1.71-1.73 (m, 1H), 1.54 (s, 3H), 1.07 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+)m / z443.3 [(M+H) + , calcd. C 21 H 23 F5N4Om / z442.1].

[0407]

[0408] Example 24: (S)-1-((2-(difluoromethyl)-6-(4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((2-(difluoromethyl)-6-(4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

[0409]

[0410] Example 24 was prepared according to a procedure similar to that described for Example 13.

[0411] Part C: (S)-1-((2-(difluoromethyl)-6-(4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0412]

[0413] This compound was prepared using (S)-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and tert-butyl 4-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (161.1 mg, 0.44 mmol) to obtain a pale-brown powder (20.4 mg, 17.5%). 1 H NMR (500 MHz, MeOD) δ8.23-8.25 (d, 1H), 7.92-7.95 (m, 2H), 7.66 (d, 1H), 7.92-7.13 (m, 2H), 4.04-4.12 (m, 2H), 1.82-1.91 (m, 1H), 1.71-1.75 (m, 1H), 1.59-1.63 (m, 1H), 1.39 (s, 3H), 1.03 (d, 3H), 1.10 (d, 3H). LC-MS (ESI+)m / z393.1 [(M+H) + , calcd. C 20 H 23 F3N4Om / z392.1].

[0414]

[0415] Example 25: ((S)-1-((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [((S)-1-((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

[0416]

[0417] Example 25 was prepared according to a procedure similar to that described for Example 13.

[0418] Part C: ((S)-1-((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0419]

[0420] This compound was prepared using (S)-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 14, Part B) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (153.1 mg, 0.44 mmol) to obtain an ivory powder (30.9 mg, 27.8%). 1 H NMR (500 MHz, MeOD) δ8.87 (d, 1H), 8.22 (d, 1H), 7.96 (s, 1H), 7.88 (m, 1H), 7.56 (d, 1H), 7.18-7.20 (m, 1H), 6.91-7.13 (m, 1H), 3.89-3.95 (m, 2H), 1.78-1.82 (m, 1H), 1.49-1.61 (m, 2H), 1.26 (s, 3H), 0.98 (d, 3H), 0.98 (d, 3H). LC-MS (ESI+)m / z375.2 [(M+H) + , calcd. C 20 H 24 F2N4Om / z374.1].

[0421]

[0422] Example 26: (S)-1-((6-(5-chloro-1H-pyrazolo[3,4-b]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((6-(5-chloro-1H-pyrazolo[3,4-b]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

[0423]

[0424] Example 26 was prepared according to a procedure similar to that described for Example 8.

[0425] Part B: (S)-1-((6-(5-chloro-1H-pyrazolo[3,4-b]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0426]

[0427] This compound was prepared using (S)-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and 5-chloro-1-(tetrahydro-2H-pyran-2-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazolo[3,4-b]pyridine (161.7 mg, 0.44 mmol) to obtain a pale-yellow powder (40.2 mg, 33.0%). 1 H NMR (500 MHz, MeOD) δ8.95 (d, 1H), 8.50 (d, 1H), 8.32 (d, 1H), 7.77 (d, 1H), 7.13-7.36 (m, 1H), 4.17-4.31 (m, 2H), 1.82-1.88 (m, 2H), 1.69-1.71 (m, 1H), 1.52 (s, 3H), 1.06 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+)m / z410.2 [(M+H) + , calcd. C19 H 22 ClF2N5Om / z409.1].

[0428]

[0429] Example 27: (S)-1-((2-(difluoromethyl)-6-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((2-(difluoromethyl)-6-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

[0430]

[0431] Example 27 was prepared according to a procedure similar to that described for Example 13.

[0432] Part C: (S)-1-((2-(difluoromethyl)-6-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0433]

[0434] This compound was prepared using (S)-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and tert-butyl 4-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (166.4 mg, 0.44 mmol) to obtain a pale-yellow powder (34.9 mg, 29.1%). 1H NMR (500 MHz, MeOD) δ8.23 (m, 1H), 8.12 (d, 1H), 7.80 (d, 1H), 7.48-7.51 (m, 2H), 7.13-7.36 (m, 1H), 4.17-4.31 (m, 2H), 3.91 (s, 3H), 1.82-1.88 (m, 2H), 1.69-1.71 (m, 1H), 1.52 (s, 3H), 1.06 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+)m / z405.6 [(M+H) + , calcd. C 21 H 26 F2N4O2m / z404.2].

[0435]

[0436] Example 28: (S)-1-((2-(difluoromethyl)-6-(6-fluoro-1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((2-(difluoromethyl)-6-(6-fluoro-1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

[0437]

[0438] Example 28 was prepared according to a similar procedure as described for Example 10 using (S)-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and 6-fluoro-1H-pyrrolo[3,2-b]pyridine (440.3 mg, 0.30 mmol) to obtain an ivory powder (20.4 mg, 17.5%). 1H NMR (500 MHz, MeOD) δ8.66-8.69 (m, 1H), 8.32 (s, 1H), 8.16 (d, 1H), 7.82 (s, 2H), 7.04-7.26 (m, 1H), 6.80 (d, 1H), 4.06-4.16 (m, 2H), 1.70-1.81 (m, 2H), 1.57-1.61 (m, 1H), 1.39 (s, 3H), 0.99 (d, 3H), 0.95 (d, 3H). LC-MS (ESI+)m / z393.4 [(M+H) + , calcd. C 20 H 23 F3N4Om / z392.1].

[0439]

[0440] Example 29: (S)-1-((2-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((2-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

[0441]

[0442] Example 29 was prepared according to a similar procedure as described for Example 10 using (S)-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and 1H-pyrrolo[3,2-b]pyridine (35.0 mg, 0.30 mmol) to obtain an ivory powder (24.7 mg, 22.2%). 1H NMR (500 MHz, MeOD) δ8.91 (d, 1H), 8.42 (d, 1H), 8.22 (d, 1H), 7.90-7.92 (m, 2H), 7.32-7.35 (m, 1H), 6.88-7.23 (m, 2H), 4.22-4.32 (m, 2H), 1.85-1.88 (m, 2H), 1.68-1.73 (m, 1H), 1.53 (s, 3H), 1.07 (d, 3H), 1.03 (d, 3H). LC-MS (ESI+)m / z375.1 [(M+H) + , calcd. C 20 H 24 F2N4Om / z374.1].

[0443]

[0444] Example 30: (S)-1-((4-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((4-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

[0445]

[0446] Example 30 was prepared according to a procedure similar to that described for Example 13.

[0447] Part A: 2-Bromo-4-(difluoromethyl)-5-fluoropyridine

[0448]

[0449] This compound was prepared using 2-bromo-5-fluoroisonicotinaldehyde (2.0 g, 9.80 mmol) and diethylaminosulfur trifluoride (2.8 mL, 19.6 mmol), and a pale-yellow liquid (1.6 g, 75.3%) was obtained. LC-MS (ESI+) m / z 226.6 [(M+H) + , calcd. C6H3BrF3Nm / z224.9].

[0450]

[0451] Part B: (S)-1-((6-bromo-4-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0452]

[0453] This compound was prepared using (S)-2-amino-2,4-dimethylpentan-1-ol (319.3 mg, 2.43 mmol) and 2-bromo-4-(difluoromethyl)-5-fluoropyridine (500.0 mg, 2.21 mmol) (Example 30, Part A) and a pale-yellow liquid (488.6 mg, 76.9%) was obtained. LC-MS (ESI+) m / z 337.2 [(M+H) + , calcd. C 13 H 19 BrF2N2Om / z336.0].

[0454]

[0455] Part C: (S)-1-((4-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0456]

[0457] This compound was prepared using (S)-1-((6-bromo-4-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 30, Part B) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (130.8 mg, 0.44 mmol) to obtain a pale-brown powder (28.3 mg, 29.4%). 1H NMR (500 MHz, MeOD) δ8.57 (s, 1H), 8.46 (s, 2H), 8.27 (s, 1H), 7.22-7.44 (m, 1H), 4.36-4.45 (m, 2H), 1.82-1.86 (m, 2H), 1.65-1.70 (m, 1H), 1.50 (s, 3H), 1.04 (d, 3H), 0.98 (d, 3H). LC-MS (ESI+)m / z325.2 [(M+H) + , calcd. C 16 H 22 F2N4Om / z324.1].

[0458]

[0459] Example 31: (S)-1-((4-(difluoromethyl)-6-(2H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((4-(difluoromethyl)-6-(2H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

[0460]

[0461] Example 31 was prepared according to a procedure similar to that described for Example 8.

[0462] Part B: (S)-1-((4-(difluoromethyl)-6-(2H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0463]

[0464] This compound was prepared using (S)-1-((6-bromo-4-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 30, Part B) and 2-(tetrahydro-2H-pyran-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-1,2,3-triazole (124.1 mg, 0.44 mmol) and an ivory powder (17.8 mg, 18.4%) was obtained. 1 H NMR (500 MHz, MeOD) δ8.72 (s, 1H), 8.64 (s, 1H), 8.42 (s, 1H), 7.28-7.49 (m, 1H), 4.44-4.52 (m, 2H), 1.87-1.92 (m, 2H), 1.72-1.75 (m, 1H), 1.55 (s, 3H), 1.08 (d, 3H), 1.04 (d, 3H). LC-MS (ESI+)m / z326.5 [(M+H) + , calcd. C 15 H 21 F2N5Om / z325.1].

[0465]

[0466] Example 32: ((S)-1-((4-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [((S)-1-((4-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

[0467]

[0468] Example 32 was prepared according to a procedure similar to that described for Example 13.

[0469] Part C: ((S)-1-((4-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0470]

[0471] This compound was prepared using (S)-1-((6-bromo-4-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 30, Part B) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (153.1 mg, 0.44 mmol) to obtain a pale-brown powder (34.2 mg, 30.8%). 1 H NMR (500 MHz, MeOD) δ8.87 (d, 1H), 8.22 (d, 1H), 7.96 (s, 1H), 7.88 (m, 1H), 7.56 (d, 1H), 7.18-7.20 (m, 1H), 6.91-7.13 (m, 1H), 4.44-4.52 (m, 2H), 1.87-1.92 (m, 2H), 1.72-1.75 (m, 1H), 1.55 (s, 3H), 1.08 (d, 3H), 1.04 (d, 3H). LC-MS (ESI+)m / z375.4 [(M+H) + , calcd. C 20 H 24 F2N4Om / z374.1].

[0472]

[0473] Example 33: (S)-1-((5-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((5-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

[0474]

[0475] Example 33 was prepared according to a procedure similar to that described for Example 13.

[0476] Part A: 2-Bromo-3-(difluoromethyl)-5-fluoropyridine

[0477]

[0478] This compound was prepared using 2-bromo-5-fluoronicotinaldehyde (3.0 g, 14.71 mmol) and diethylaminosulfur trifluoride (4.2 mL, 29.41 mmol) and a pale-yellow liquid (2.5 g, 77.0%) was obtained. LC-MS (ESI+) m / z 287.3 [(M+H) + , calcd. C6H3BrF3Nm / z224.9].

[0479]

[0480] Part B: (S)-1-((6-bromo-5-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0481]

[0482] This compound was prepared using (S)-2-amino-2,4-dimethylpentan-1-ol (0.6 g, 4.87 mmol) and 2-bromo-3-(difluoromethyl)-5-fluoropyridine (1.0 g, 4.42 mmol) (Example 33, Part A) and a pale-yellow liquid (0.26 g, 17.4%) was obtained. LC-MS (ESI+) m / z 337.4 [(M+H) + , calcd. C 13 H 19 BrF2N2Om / z336.0].

[0483]

[0484] Part C: (S)-1-((5-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0485]

[0486] This compound was prepared using (S)-1-((6-bromo-5-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 33, Part B) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (153.1 mg, 0.44 mmol) to obtain a pale-brown powder (26.5 mg, 23.8%). 1 H NMR (500 MHz, MeOD) δ8.56-8.59 (m, 1H), 8.25-8.28 (m, 1H), 7.66-7.81 (m, 2H), 7.17-7.21 (m, 1H), 5.39-5.9 (m, 2H), 4.42-4.44 (m, 2H), 1.82-1.88 (m, 1H), 1.56-1.68 (m, 2H), 1.34 (s, 3H), 1.01 (d, 3H), 1.00 (d, 3H). LC-MS (ESI+)m / z375.3 [(M+H) + , calcd. C 20 H 24 F2N4Om / z374.1].

[0487]

[0488] Example 34: (S)-1-((6-(1H-pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((6-(1H-pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

[0489]

[0490] Example 34 was prepared according to a procedure similar to that described for Example 13.

[0491] Part B: (S)-1-((6-bromo-2-(trifluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0492]

[0493] This compound was prepared using (S)-2-amino-2,4-dimethylpentan-1-ol (295.8 mg, 2.25 mmol) and 6-bromo-3-fluoro-2-(trifluoromethyl)pyridine (500.0 mg, 2.05 mmol) and obtained as an off-white powder (642.5 mg, 88.2%). LC-MS (ESI+) m / z 355.7 [(M+H) + , calcd. C 13 H 18 BrF3N2Om / z354.0].

[0494]

[0495] Part C: (S)-1-((6-(1H-pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0496]

[0497] This compound was prepared using (S)-1-((6-bromo-2-(trifluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.28 mmol) (Example 34, Part B) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (124.2 mg, 0.42 mmol) to obtain a pale-brown powder (26.5 mg, 27.4%). 1 H NMR (500 MHz, MeOD) δ8.09 (br, 2H), 7.82 (d, 1H), 7.62 (d, 1H), 3.92-3.97 (m, 2H), 1.78-1.81 (m, 1H), 1.43-1.60 (m, 2H), 1.28 (s, 3H), 0.98 (d, 3H), 0.96 (d, 3H). LC-MS (ESI+)m / z343.6 [(M+H) + , calcd. C 16 H 21 F3N4Om / z342.1].

[0498]

[0499] Example 35: (S)-1-((6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

[0500]

[0501] Example 35 was prepared according to a procedure similar to that described for Example 13.

[0502] Part C: (S)-1-((6-(5-Fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0503]

[0504] This compound was prepared using (S)-1-((6-bromo-2-(trifluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.28 mmol) (Example 34, Part B) and tert-butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (152.9 mg, 0.42 mmol) to obtain an ivory powder (30.2 mg, 26.1%). 1 H NMR (500 MHz, MeOD) δ8.59-8.61 (m, 1H), 8.16 (s, 1H), 8.09 (s, 1H), 7.98 (d, 1H), 7.65 (d, 1H), 3.93-3.98 (m, 2H), 1.81-1.85 (m, 1H), 1.57-1.61 (m, 1H), 1.50-1.57 (m, 1H), 1.27 (s, 3H), 1.00 (d, 3H), 0.98 (d, 3H). LC-MS (ESI+)m / z411.4 [(M+H)+ , calcd. C 20 H 22 F4N4Om / z410.1].

[0505]

[0506] Example 36: (S)-1-((5-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((5-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine]

[0507]

[0508] Example 36 was prepared according to a procedure similar to that described for Example 13.

[0509] Part B: (S)-1-((5-bromopyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine

[0510]

[0511] This compound was prepared using (S)-2-amino-2,4-dimethylpentan-1-ol (246.0 mg, 1.88 mmol) and 5-bromo-2-fluoropyridine (300.0 mg, 1.70 mmol) and a pale-yellow liquid (280.4 mg, 57.2%) was obtained. LC-MS (ESI+) m / z 287.3 [(M+H) + , calcd. C 12 H 19 BrN2Om / z286.0].

[0512]

[0513] Part C: (S)-1-((5-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine

[0514]

[0515] This compound was prepared using (S)-1-((5-bromopyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 36, Part B) and tert-butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (189.1 mg, 0.52 mmol) and an ivory powder (20.7 mg, 17.3%) was obtained. 1 H NMR (500 MHz, MeOD) δ8.51 (s, 1H), 8.34-8.40 (m, 2H), 8.14-8.15 (m, 1H), 7.93-7.94 (m, 1H), 7.13-7.14 (m, 1H) 4.42-4.50 (m, 2H), 1.80-1.89 (m, 2H), 1.67-1.71 (m, 1H), 1.49 (s, 3H), 1.02 (d, 3H), 1.06 (d, 3H). LC-MS (ESI+)m / z343.4 [(M+H) + , calcd. C 19 H 23 FN4Om / z342.1].

[0516]

[0517] Example 37: (S)-1-((3-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((3-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine]

[0518]

[0519] Example 37 was prepared according to a procedure similar to that described for Example 13.

[0520] Part B: (S)-1-((3-bromopyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine

[0521]

[0522] This compound was prepared using (S)-2-amino-2,4-dimethylpentan-1-ol (246.0 mg, 1.88 mmol) and 3-bromo-2-fluoropyridine (300.0 mg, 1.70 mmol) and a pale-yellow liquid (267.8 mg, 54.7%) was obtained. LC-MS (ESI+) m / z 287.2 [(M+H) + , calcd. C 12 H 19 BrN2Om / z286.0].

[0523]

[0524] Part C: (S)-1-((3-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine

[0525]

[0526] This compound was prepared using (S)-1-((3-bromopyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 37, Part B) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (179.7 mg, 0.52 mmol) and an ivory powder (21.5 mg, 19.0%) was obtained. 1 H NMR (500 MHz, MeOD) δ8.25 (d, 1H), 8.10-8.15 (m, 2H), 7.97-7.98 (m, 1H), 7.77 (s, 1H), 7.13-7.19 (m, 2H), 4.46-4.61 (m, 2H), 1.76-1.78 (m, 1H), 1.66-1.70 (m, 1H), 1.51-1.55 (m, 1H), 1.38 (s, 3H), 0.92 (d, 3H), 0.87 (d, 3H). LC-MS (ESI+)m / z325.4 [(M+H) + , calcd. C 19 H 24 N4Om / z324.1].

[0527]

[0528] Example 38: (S)-1-((4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine]

[0529]

[0530] Example 38 was prepared according to a procedure similar to that described for Example 13.

[0531] Part B: (S)-1-((4-bromopyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine

[0532]

[0533] This compound was prepared using (S)-2-amino-2,4-dimethylpentan-1-ol (246.0 mg, 1.88 mmol) and 4-bromo-2-fluoropyridine (300.0 mg, 1.70 mmol) and a pale-yellow liquid (360.2 mg, 73.5%) was obtained. LC-MS (ESI+) m / z 287.1 [(M+H) + , calcd. C 12 H 19 BrN2Om / z286.0].

[0534]

[0535] Part C: (S)-1-((4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine

[0536]

[0537] This compound was prepared using (S)-1-((4-bromopyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 38, Part B) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (179.7 mg, 0.52 mmol) and an ivory powder (28.6 mg, 25.3%) was obtained. 1 H NMR (500 MHz, MeOD) δ8.42 (d, 1H), 8.30 (d, 1H), 8.17 (d, 1H), 7.97 (s, 1H), 7.41 (d, 1H), 7.25-7.27 (m, 2H), 4.37-4.46 (m, 2H), 1.81-1.90 (m, 2H), 1.67-1.71 (m, 1H), 1.49 (s, 3H), 1.06 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+)m / z000.0 [(M+H) + , calcd. C 19 H 24 N4Om / z324.1].

[0538]

[0539] Example 39: (S)-1-((6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine]

[0540]

[0541] Example 39 was prepared according to a procedure similar to that described for Example 13.

[0542] Part B: (S)-1-((6-bromopyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine

[0543]

[0544] This compound was prepared using (S)-2-amino-2,4-dimethylpentan-1-ol (246.0 mg, 1.88 mmol) and 2-bromo-6-fluoropyridine (300.0 mg, 1.70 mmol) and a pale-yellow liquid (282.3 mg, 57.6%) was obtained. LC-MS (ESI+) m / z 287.1 [(M+H) + , calcd. C 12 H 19 BrN2Om / z286.0].

[0545]

[0546] Part C: (S)-1-((6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine

[0547]

[0548] This compound was prepared using (S)-1-((6-bromopyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 39, Part B) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (179.7 mg, 0.52 mmol) and an ivory powder (20.7 mg, 18.3%) was obtained. 1 H NMR (500 MHz, MeOD) δ8.86 (d, 1H), 8.30 (d, 1H), 8.09 (s, 1H), 7.76 (t, 1H), 7.50 (d, 1H), 7.24-7.27 (m, 1H), 6.77 (d, 1H), 4.54-4.63 (m, 2H), 1.85-1.96 (m, 2H), 1.73-1.77 (m, 1H), 1.56 (s, 3H), 1.11 (d, 3H), 1.08 (d, 3H). LC-MS (ESI+)m / z000.0 [(M+H) + , calcd. C 19 H 24 N4Om / z324.1].

[0549]

[0550] Example 40: (S)-1-((4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

[0551]

[0552] Example 40 was prepared according to a procedure similar to that described for Example 13.

[0553] Part B: (S)-1-((4-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0554]

[0555] This compound was prepared using (S)-2-amino-2,4-dimethylpentan-1-ol (246.0 mg, 1.88 mmol) and 4-bromo-3-fluoropyridine (300.0 mg, 1.70 mmol) and a pale-yellow liquid (246.4 mg, 50.3%) was obtained. LC-MS (ESI+) m / z 287.1 [(M+H) + , calcd. C 12 H 19 BrN2Om / z286.0].

[0556]

[0557] Part C: (S)-1-((4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0558]

[0559] This compound was prepared using (S)-1-((4-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 40, Part B) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (179.7 mg, 0.52 mmol) to obtain an ivory powder (25.9 mg, 22.9%). 1 H NMR (500 MHz, MeOD) δ8.90 (d, 2H), 8.61 (d, 1H), 8.58 (d, 1H), 8.52 (s, 1H), 8.34 (d, 1H), 7.68-7.70 (m, 1H), 4.46-4.53 (m, 2H), 1.73-1.81 (m, 2H), 1.46-1.66 (m, 1H), 1.46 (s, 3H), 0.96 (d, 3H), 0.88 (d, 3H). LC-MS (ESI+)m / z325.4 [(M+H) + , calcd. C 19 H 24 N4Om / z324.1].

[0560]

[0561] Example 41: (S)-1-((5-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((5-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

[0562]

[0563] Example 41 was prepared according to a procedure similar to that described for Example 13.

[0564] Part B: (S)-1-((5-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0565]

[0566] This compound was prepared using (S)-2-amino-2,4-dimethylpentan-1-ol (246.0 mg, 1.88 mmol) and 3-bromo-5-fluoropyridine (300.0 mg, 1.70 mmol) and a pale-yellow liquid (324.1 mg, 66.2%) was obtained. LC-MS (ESI+) m / z 287.3 [(M+H) + , calcd. C 12 H 19 BrN2Om / z286.0].

[0567]

[0568] Part C: (S)-1-((5-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0569]

[0570] This compound was prepared using (S)-1-((5-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 41, Part B) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (179.7 mg, 0.52 mmol) to obtain an ivory powder (19.7 mg, 17.4%). 1 H NMR (500 MHz, MeOD) δ9.05 (d, 1H), 8.95 (s, 1H), 8.65 (d, 2H), 8.54 (d, 1H), 8.43 (s, 1H), 7.69 (t, 1H), 4.45-4.52 (m, 2H), 1.83-1.92 (m, 2H), 1.71-1.75 (m, 1H), 1.53 (s, 3H), 1.05 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+)m / z000.0 [(M+H) + , calcd. C 19 H 24 N4Om / z324.1].

[0571]

[0572] Example 42: (S)-1-((3-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-4-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((3-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-4-yl)oxy)-2,4-dimethylpentan-2-amine]

[0573]

[0574] Example 42 was prepared according to a procedure similar to that described for Example 13.

[0575] Part B: (S)-1-((3-bromopyridin-4-yl)oxy)-2,4-dimethylpentan-2-amine

[0576]

[0577] This compound was prepared using (S)-2-amino-2,4-dimethylpentan-1-ol (246.0 mg, 1.88 mmol) and 3-bromo-4-fluoropyridine (300.0 mg, 1.70 mmol) and a pale-yellow liquid (283.3 mg, 57.6%) was obtained. LC-MS (ESI+) m / z 287.3 [(M+H) + , calcd. C 12 H 19 BrN2Om / z286.0].

[0578]

[0579] Part C: (S)-1-((3-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-4-yl)oxy)-2,4-dimethylpentan-2-amine

[0580]

[0581] This compound was prepared using (S)-1-((3-bromopyridin-4-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 42, Part B) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (179.7 mg, 0.52 mmol) and an ivory powder (18.6 mg, 16.4%) was obtained. 1 H NMR (500 MHz, MeOD) δ8.92 (s, 1H), 8.83 (d, 1H), 8.70 (d, 1H), 8.54 (d, 1H), 8.15 (s, 1H), 7.92 (d, 1H), 7.60-7.63 (m, 1H), 4.57-4.63 (m, 2H), 1.75-1.78 (m, 1H), 1.52-1.65 (m, 2H), 1.37 (s, 3H), 0.92 (d, 3H), 0.90 (d, 3H). LC-MS (ESI+)m / z000.0 [(M+H) + , calcd. C 19 H 24 N4Om / z324.1].

[0582]

[0583] Example 43: (S)-1-((2-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-4-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((2-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-4-yl)oxy)-2,4-dimethylpentan-2-amine]

[0584]

[0585] Example 43 was prepared according to a procedure similar to that described for Example 13.

[0586] Part B: (S)-1-((2-bromopyridin-4-yl)oxy)-2,4-dimethylpentan-2-amine

[0587]

[0588] This compound was prepared using (S)-2-amino-2,4-dimethylpentan-1-ol (246.0 mg, 1.88 mmol) and 2-bromo-4-fluoropyridine (300.0 mg, 1.70 mmol) and a pale-yellow liquid (292.1 mg, 59.6%) was obtained. LC-MS (ESI+) m / z 287.3 [(M+H) + , calcd. C 12 H 19 BrN2Om / z286.0].

[0589]

[0590] Part C: (S)-1-((2-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-4-yl)oxy)-2,4-dimethylpentan-2-amine

[0591]

[0592] This compound was prepared using (S)-1-((2-bromopyridin-4-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 43, Part B) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (179.7 mg, 0.52 mmol) to obtain an ivory powder (19.8 mg, 17.5%). 1 H NMR (500 MHz, MeOD) δ8.85 (d, 1H), 8.64 (d, 1H), 8.53 (d, 1H), 8.47 (s, 1H), 7.89 (s, 1H), 7.49-7.61 (m, 2H), 4.52-4.60 (m, 2H), 1.82-1.89 (m, 2H), 1.71-1.74 (m, 1H), 1.53 (s, 3H), 1.05 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+)m / z325.3 [(M+H) + , calcd. C 19 H 24 N4Om / z324.1].

[0593]

[0594] Example 44: (S)-1-((2-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((2-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

[0595]

[0596] Example 44 was prepared according to a procedure similar to that described for Example 13.

[0597] Part B: (S)-1-((2-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0598]

[0599] This compound was prepared using (S)-2-amino-2,4-dimethylpentan-1-ol (246.0 mg, 1.88 mmol) and 2-bromo-3-fluoropyridine (300.0 mg, 1.70 mmol) and a pale-yellow liquid (197.5 g, 40.3%) was obtained. LC-MS (ESI+) m / z 287.1 [(M+H) + , calcd. C 12 H 19 BrN2Om / z286.0].

[0600]

[0601] Part C: (S)-1-((2-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

[0602]

[0603] This compound was prepared using (S)-1-((2-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 44, Part B) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (179.7 mg, 0.52 mmol) to obtain an ivory powder (21.6 mg, 19.1%). 1 H NMR (500 MHz, MeOD) δ8.79 (d, 1H), 8.48-8.53 (m, 2H), 8.41 (d, 1H), 8.33 (t, 1H), 7.86-7.89 (m, 1H), 7.57-7.60 (m, 1H), 4.37-4.43 (m, 2H), 1.65-1.77 (m, 2H), 1.55-1.59 (m, 1H), 1.40 (s, 3H), 0.92 (d, 3H), 0.85 (d, 3H). LC-MS (ESI+)m / z325.3[(M+H) + , calcd. C 19 H 24 N4Om / z324.1].

[0604]

[0605] Example 45: 1-((2-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine [1-((2-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]

[0606]

[0607] Example 45 was prepared according to a procedure similar to that described for Example 13.

[0608] Part B: 1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine

[0609]

[0610] This compound was prepared using 2-amino-2-methylpropan-1-ol (0.4 g, 4.87 mmol) and 6-bromo-2-(difluoromethyl)-3-fluoropyridine (1.0 g, 4.42 mmol) (Example 13, Part A) and a clear liquid (0.8 g, 61.2%) was obtained. LC-MS (ESI+) m / z 295.4 [(M+H) + , calcd. C 10 H 13 BrF2N2Om / z294.0].

[0611]

[0612] Part C: 1-((2-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine

[0613]

[0614] This compound was prepared using 1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine (100.0 mg, 0.34 mmol) (Example 45, Part B) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (149.5 mg, 0.51 mmol) to obtain an ivory powder (62.2 mg, 65.0%). 1 H NMR (500 MHz, MeOD) δ8.53 (s, 2H), 7.93 (d, 1H), 7.74 (d, 1H), 7.03-7.24 (m, 1H), 4.20 (s, 2H), 1.52 (s, 6H). LC-MS (ESI+)m / z283.4 [(M+H)+, calcd. C 13 H 16 F2N4Om / z282.1].

[0615]

[0616] Example 46: 1-((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine [1-((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]

[0617]

[0618] Example 46 was prepared according to a procedure similar to that described for Example 13.

[0619] Part C: 1-((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine

[0620]

[0621] This compound was prepared using 1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine (100.0 mg, 0.34 mmol) (Example 45, Part B) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (174.9 mg, 0.51 mmol) to obtain an ivory powder (25.8 mg, 26.9%). 1 H NMR (500 MHz, MeOD) δ8.87 (d, 1H), 8.20 (d, 1H), 7.96 (s, 1H), 7.88 (d, 1H), 7.57 (d, 1H), 6.94-7.19 (m, 2H), 3.96 (s, 2H), 1.33 (s, 6H). LC-MS (ESI+)m / z332.4 [(M+H) + , calcd. C17H18F2N4Om / z332.1].

[0622]

[0623] Example 47: 1-((2-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine [1-((2-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]

[0624]

[0625] Example 47 was prepared according to a procedure similar to that described for Example 13.

[0626] Part C: 1-((2-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine

[0627]

[0628] This compound was prepared using 1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine (100.0 mg, 0.34 mmol) (Example 45, Part B) and tert-butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (184.0 mg, 0.51 mmol) to obtain a pale-yellow powder (49.1 mg, 41.3%). 1 H NMR (500 MHz, MeOD) δ9.16-9.18 (m, 1H), 8.49-8.50 (m, 1H), 8.33 (s, 1H), 8.03 (d, 1H), 7.73 (d, 1H), 7.13-7.34 (m, 1H), 4.19 (s, 2H), 1.51 (s, 6H). LC-MS (ESI+)m / z351.5 [(M+H) + , calcd. C 17 H 17 F3N4Om / z350.1].

[0629]

[0630] Example 48: 1-((2-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine [1-((2-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]

[0631]

[0632] Example 48 was prepared according to a similar procedure as described for Example 10 using 1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine (100.0 mg, 0.34 mmol) (Example 45, Part B) and 1H-pyrrolo[3,2-b]pyridine (40.0 mg, 0.34 mmol) to obtain an off-white powder (16.9 mg, 15.0%). 1 H NMR (500 MHz, MeOD) δ9.52 (d, 1H), 8.69-8.73 (m, 2H), 7.99-8.06 (m, 2H), 7.82-7.85 (m, 1H), 7.18-7.39 (m, 1H), 7.13 (d, 1H), 4.26 (s, 2H), 1.15 (m, 6H). LC-MS (ESI+)m / z333.4 [(M+H) + , calcd. C 17 H 18 F2N4Om / z332.1].

[0633]

[0634] Example 49: 1-((6-(1H-pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine [1-((6-(1H-pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]

[0635]

[0636] Example 49 was prepared according to a procedure similar to that described for Example 13.

[0637] Part B: tert-Butyl (1-((6-bromo-2-(trifluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-yl)carbamate

[0638]

[0639] This compound was prepared using 2-amino-2-methylpropan-1-ol (0.4 g, 4.51 mmol) and 6-bromo-3-fluoro-2-(trifluoromethyl)pyridine (1.0 g, 4.10 mmol) and a clear liquid (0.7 g, 54.7%) was obtained. LC-MS (ESI+) m / z 313.3 [(M+H) + , calcd. C 10 H 12 BrF3N2Om / z312.0].

[0640]

[0641] Part C: 1-((6-(1H-pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine

[0642]

[0643] This compound was prepared using 1-((6-bromo-2-(trifluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine (100.0 mg, 0.32 mmol) (Example 49, Part B) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (140.9 mg, 0.48 mmol) to obtain an ivory powder (24.8 mg, 25.8%). 1 H NMR (500 MHz, MeOD) 8.41 (s, 2H), 7.96 (d, 1H), 7.78 (d, 1H), 4.17 (s, 2H), 1.47 (s, 6H). LC-MS (ESI+)m / z301.1 [(M+H) + , calcd. C 13 H15 F3N4Om / z300.1].

[0644]

[0645] Example 50: 1-((6-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine [1-((6-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]

[0646]

[0647] Example 50 was prepared according to a procedure similar to that described for Example 13.

[0648] Part C: 1-((6-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine

[0649]

[0650] This compound was prepared using 1-((6-bromo-2-(trifluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine (100.0 mg, 0.32 mmol) (Example 49, Part B) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (164.9 mg, 0.48 mmol) to obtain a pale-yellow powder (24.1 mg, 21.5%). 1 H NMR (500 MHz, MeOD) δ9.58 (d, 1H), 8.52 (d, 1H), 8.42 (s, 1H), 8.23 ​​(d, 1H), 7.89 (d, 1H), 7.70-7.73 (m, 1H), 4.25 (s, 2H), 1.53 (s, 6H). LC-MS (ESI+)m / z000.0 [(M+H) + , calcd. C 17 H 17 F3N4Om / z350.1].

[0651]

[0652] Example 51: 2-((6-(5-chloro-1H-pyrazolo[3,4-b]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-ol [2-((6-(5-chloro-1H-pyrazolo[3,4-b]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-ol]

[0653]

[0654] Example 51 was prepared according to a procedure similar to that described for Example 13.

[0655] Part B: 2-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-ol

[0656]

[0657] This compound was prepared using ethane-1,2-diol (151.0 mg, 2.43 mmol) and 6-bromo-2-(difluoromethyl)-3-fluoropyridine (500.0 mg, 2.21 mmol) (Example 13, Part A) and a clear liquid (280.4 mg, 40.6%) was obtained. LC-MS (ESI+) m / z 267.0 [(M+H) + , calcd. C8H8BrF2NO2m / z266.9].

[0658]

[0659] Example 51 was prepared according to a procedure similar to that described for Example 8.

[0660] Part B: 2-((6-(5-chloro-1H-pyrazolo[3,4-b]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-ol

[0661]

[0662] This compound was prepared using 2-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-ol (100.0 mg, 0.37 mmol) (Example 51, Part B) and 5-chloro-1-(tetrahydro-2H-pyran-2-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazolo[3,4-b]pyridine (203.4 mg, 0.56 mmol) and a yellow powder (20.8 mg, 16.3%) was obtained. 1 H NMR (500 MHz, MeOD) δ9.01 (d, 1H), 8.52 (d, 1H), 8.29 (d, 1H), 7.72 (d, 1H), 7.09-7.31 (m, 1H), 4.25-4.27 (m, 2H), 3.95-3.97 (m, 2H). LC-MS (ESI+)m / z341.5 [(M+H) + , calcd. C 14 H 11 ClF2N4O2m / z340.0].

[0663]

[0664] Example 52: 2-((6-(5-chloro-1H-pyrazolo[3,4-b]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-amine [2-((6-(5-chloro-1H-pyrazolo[3,4-b]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-amine]

[0665]

[0666] Example 52 was prepared according to a procedure similar to that described for Example 13.

[0667] Part B: 2-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-amine

[0668]

[0669] This compound was prepared using 2-aminoethanol-1-ol (148.6 mg, 2.43 mmol) and 6-bromo-2-(difluoromethyl)-3-fluoropyridine (500.0 mg, 2.21 mmol) (Example 13, Part A) and a clear liquid (325.4 mg, 55.0%) was obtained. LC-MS (ESI+) m / z 266.3 [(M+H) + , calcd. C8H9BrF2N2Om / z265.9].

[0670]

[0671] Example 52 was prepared according to a procedure similar to that described for Example 8.

[0672] Part B: 2-((6-(5-chloro-1H-pyrazolo[3,4-b]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-amine

[0673]

[0674] This compound was prepared using 2-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-amine (100.0 mg, 0.37 mmol) (Example 52, Part B) and 5-chloro-1-(tetrahydro-2H-pyran-2-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazolo[3,4-b]pyridine (204.2 mg, 0.56 mmol) and a yellow powder (33.6 mg, 26.4%) was obtained. 1 H NMR (500 MHz, MeOD) δ8.97 (d, 1H), 8.51 (d, 1H), 8.32 (d, 1H), 7.76 (d, 1H), 7.14-7.35 (m, 1H), 4.43-4.45 (m, 2H), 3.47-3.49 (m, 2H). LC-MS (ESI+)m / z340.3 [(M+H) + , calcd. C 14 H 12 ClF2N5Om / z339.0].

[0675]

[0676] Example 53: (S)-1-((4-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((4-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine]

[0677]

[0678] Example 53 was prepared according to a similar procedure as described for Example 10 using (S)-1-((4-bromopyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 38, Part B) and 1H-pyrrolo[3,2-b]pyridine (41.1 mg, 0.35 mmol) to obtain a pale-brown powder (22.5 mg, 19.9%). 1 H NMR (500 MHz, MeOD) δ8.90 (d, 1H), 8.75 (d, 1H), 8.51 (d, 1H), 8.42 (d, 1H), 7.83-7.85 (m, 1H), 7.43 (d, 1H), 7.31 (s, 1H), 7.19 (d, 1H), 4.47-4.55 (m, 2H), 1.80-1.89 (m, 2H), 1.67-1.71 (m, 1H), 1.49 (s, 3H), 1.05 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+)m / z325.5 [(M+H) + , calcd. C 19 H 24 N4Om / z324.1].

[0679]

[0680] Example 54: (S)-1-((5-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((5-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

[0681]

[0682] Example 54 was prepared according to a similar procedure as described for Example 10 using (S)-1-((5-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 41, Part B) and 1H-pyrrolo[3,2-b]pyridine (41.1 mg, 0.35 mmol) to obtain a pale-brown powder (19.7 mg, 17.4%). 1 H NMR (500 MHz, MeOD) δ8.74-8.77 (m, 2H), 8.61 (br, 2H), 8.47 (d, 1H), 7.93 (s, 1H), 7.81-7.83 (m, 1H), 7.19 (d, 1H), 4.26-4.35 (m, 2H), 1.82-1.89 (m, 2H), 1.69-1.73 (m, 1H), 1.51 (s, 3H), 1.07 (d, 3H), 1.03 (d, 3H). LC-MS (ESI+)m / z325.4 [(M+H) + , calcd. C 19 H 24 N4Om / z324.1].

[0683]

[0684] Example 55: (S)-1-((5-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((5-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine]

[0685]

[0686] Example 55 was prepared according to a similar procedure as described for Example 10 using (S)-1-((5-bromopyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 36, Part B) and 1H-pyrrolo[3,2-b]pyridine (41.1 mg, 0.35 mmol) to obtain a pale-brown powder (19.0 mg, 16.8%). 1 H NMR (500 MHz, MeOD) δ8.68 (d, 1H), 8.47-8.53 (m, 2H), 8.29 (d, 1H), 8.04-8.07 (m, 1H), 7.71-7.74 (m, 1H), 7.21 (d, 1H), 7.10 (d, 1H), 4.45-4.53 (m, 2H), 1.80-1.88 (m, 2H), 1.65-1.71 (m, 1H), 1.49 (s, 3H), 1.06 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+)m / z325.1 [(M+H) + , calcd. C 19 H 24 N4Om / z324.1].

[0687]

[0688] Example 56: (S)-1-(4-(1H-pyrrolo[3,2-b]pyridin-1-yl)phenoxy)-2,4-dimethylpentan-2-amine [(S)-1-(4-(1H-pyrrolo[3,2-b]pyridin-1-yl)phenoxy)-2,4-dimethylpentan-2-amine]

[0689]

[0690] Example 56 was prepared according to a similar procedure as described for Example 10 using (S)-1-(4-bromo-2-(difluoromethyl)phenoxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 22, Part B) and 1H-pyrrolo[3,2-b]pyridine (41.2 mg, 0.35 mmol) to obtain an ivory powder (20.5 mg, 18.1%).1 H NMR (500 MHz, MeOD) δ8.65 (d, 1H), 8.58 (d, 1H), 8.32 (d, 1H), 7.74-7.77 (m, 1H), 7.63 (d, 2H), 7.33 (d, 2H), 7.10 (d, 1H), 4.13-4.24 (m, 2H), 1.85-1.91 (m, 2H), 1.69-1.73 (m, 1H), 1.52 (s, 3H), 1.07 (d, 3H), 1.03 (d, 3H). LC-MS (ESI+)m / z324.2 [(M+H) + , calcd. C 20 H 25 N3Om / z323.1].

[0691]

[0692] Example 57: (S)-1-((2-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [(S)-1-((2-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]

[0693]

[0694] Example 57 was prepared according to a procedure similar to that described for Example 13.

[0695] Part B: tert-Butyl (S)-(1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate

[0696]

[0697] This compound was prepared using tert-butyl (S)-(1-hydroxy-4-methylpentan-2-yl)carbamate (1.1 g, 4.87 mmol) and 6-bromo-2-(difluoromethyl)-3-fluoropyridine (1.0 g, 4.42 mmol) (Example 13, Part A) and an off-white powder (1.1 g, 61.1%) was obtained. LC-MS (ESI+) m / z 423.3 [(M+H) + , calcd. C 17 H 25 BrF2N2O3m / z422.1].

[0698]

[0699] Part C: (S)-1-((2-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine

[0700]

[0701] This compound was prepared as an intermediate using tert-butyl (S)-(1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mmol) and tert-butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (128.3 mg, 0.35 mmol) (Example 57, Part B). After purification, hydrochloric acid (1.0 M EtOAc solution, 10 mL) was added and the mixture was stirred at room temperature for deprotection of the tert-butoxy carbonyl group. The reaction progress was monitored by HPLC. After the reaction was completed, the product was extracted with EtOAc and 10% NaOH solution (aq.). The separated organic layer was washed with water and brine, dried over magnesium sulfate, and concentrated. The residue was washed with n-hexane to obtain a pale-yellow powder (28.7 mg, 32.1%). 1H NMR (500 MHz, MeOD) 8.42-8.24 (m, 2H), 8.13 (s, 1H), 7.72 (s, 1H), 7.64 (d, 1H), 7.49-7.52 (m, 1H), 4.24-4.14 (m, 1H), 4.13-4.07 (m, 1H), 3.52-3.43 (m, 1H), 1.81-1.84 (m, 1H), 1.52-1.63 (m, 2H), 1.05 (t, 6H). LC-MS (ESI+)m / z379.3 [(M+H) + , calcd. C 19 H 21 F3N4Om / z378.1].

[0702]

[0703] Example 58: (S)-1-((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [(S)-1-((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]

[0704]

[0705] Example 58 was prepared according to a procedure similar to that described for Example 57.

[0706] Part C: (S)-1-((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine

[0707]

[0708] This compound was prepared using tert-butyl (S)-(1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 57, Part B) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (121.9 mg, 0.35 mmol) and an ivory powder (20.8 mg, 24.4%) was obtained. 1 H NMR (500 MHz, MeOD) δ8.88-8.90 (m, 1H), 8.22 (d, 1H), 7.97 (s, 1H), 7.89 (d, 1H), 7.59 (d, 1H), 7.15-7.22 (m, 1H), 6.94-7.15 (m, 1H), 4.12-4.15 (m, 1H), 3.91-3.94 (m, 1H), 1.80-1.83 (m, 1H), 1.40-1.47 (m, 2H), 1.28-1.31 (m, 1H), 0.97-1.00 (m, 6H). LC-MS (ESI+)m / z361.3 [(M+H) + , calcd. C 19 H 22 F2N4Om / z360.1].

[0709]

[0710] Example 59: (S)-1-((2-(difluoromethyl)-6-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [(S)-1-((2-(difluoromethyl)-6-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]

[0711]

[0712] Example 59 was prepared according to a procedure similar to that described for Example 57.

[0713] Part C: (S)-1-((2-(difluoromethyl)-6-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine

[0714]

[0715] This compound was prepared using tert-butyl (S)-(1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 57, Part B) and tert-butyl 4-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (132.6 mg, 0.35 mmol) to obtain an ivory powder (19.5 mg, 21.1%). 1 H NMR (500 MHz, MeOD) δ8.12 (d, 1H), 8.01 (d, 1H), 7.65 (s, 1H), 7.61 (d, 1H), 6.90-7.12 (m, 1H), 6.76 (d, 1H), 4.22-4.24 (m, 1H), 4.03-4.06 (m, 1H), 3.97 (s, 3H), 3.47-3.49 (m, 1H), 1.77-1.81 (m, 1H), 1.53-1.61 (m, 1H), 1.47-1.51 (m, 1H), 0.99 (t, 6H). LC-MS (ESI+)m / z391.4 [(M+H) + , calcd. C 20 H 24 F2N4O2m / z390.1].

[0716]

[0717] Example 60: (S)-1-((2-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [(S)-1-((2-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]

[0718]

[0719] Example 60 was prepared according to a procedure similar to that described for Example 57.

[0720] Part C: (S)-1-((2-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine

[0721]

[0722] This compound was prepared using tert-butyl (S)-(1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 57, Part B) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (104.2 mg, 0.35 mmol) to obtain an ivory powder (16.7 mg, 22.7%). 1 H NMR (500 MHz, MeOD) δ8.11 (br, 2H), 7.75 (d, 1H), 7.58 (d, 1H), 6.85-7.06 (m, 1H), 4.13-4.15 (m, 1H), 3.92-3.95 (m, 1H), 3.32-3.34 (m, 1H), 1.79-1.81 (m, 1H), 1.40-1.48 (m, 2H), 0.96-0.99 (m, 6H). LC-MS (ESI+)m / z311.3 [(M+H) + , calcd. C 15 H 20 F2N4Om / z310.1].

[0723]

[0724] Example 61: 1-((4-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine [1-((4-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]

[0725]

[0726] Example 61 was prepared according to a procedure similar to that described for Example 57.

[0727] Part B: tert-Butyl (1-((6-bromo-4-(difluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-yl)carbamate

[0728]

[0729] This compound was prepared using tert-butyl (1-hydroxy-2-methylpropan-2-yl)carbamate (1.1 g, 5.97 mmol) and 2-bromo-4-(difluoromethyl)-5-fluoropyridine (0.5 g, 2.21 mmol) (Example 30, Part A) and a clear liquid (0.4 g, 45.7%) was obtained. LC-MS (ESI+) m / z 395.1 [(M+H) + , calcd. C 15 H 21 BrF2N2O3m / z394.0].

[0730]

[0731] Part C: 1-((4-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine

[0732]

[0733] This compound was prepared using tert-butyl (1-((6-bromo-4-(difluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-yl)carbamate (100.0 mg, 0.25 mmol) (Example 61, Part B) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (130.6 mg, 0.38 mmol) to obtain a pale-yellow powder (29.5 mg, 35.0%). 1H NMR (500 MHz, MeOD) δ9.41 (d, 1H), 8.75 (s, 1H), 8.58 (d, 1H), 8.48 (s, 1H), 8.25 (s, 1H), 7.74-7.77 (m, 1H), 7.27-7.48 (m, 1H), 4.40 (s, 2H), 1.55 (s, 6H). LC-MS (ESI+)m / z000.0 [(M+H) + , calcd. C 17 H 18 F2N4Om / z332.1].

[0734]

[0735] Example 62: 1-((4-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine [1-((4-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]

[0736]

[0737] Example 62 was prepared according to a procedure similar to that described for Example 57.

[0738] Part C: 1-((4-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine

[0739]

[0740] This compound was prepared using tert-butyl (S)-(1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.25 mmol) (Example 61, Part B) and tert-butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (137.4 mg, 0.38 mmol) to obtain a pale-yellow powder (52.8 mg, 59.5%). 1 H NMR (500 MHz, MeOD) 8.70 (s, 1H), 8.44-8.52 (m, 3H), 8.35 (s, 1H), 7.31-7.53 (m, 1H), 4.43 (s, 2H), 1.54 (s, 6H). LC-MS (ESI+)m / z351.2 [(M+H) + , calcd. C 17 H 17 F3N4Om / z350.1].

[0741]

[0742] Example 63: 1-((5-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine [1-((5-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]

[0743]

[0744] Example 63 was prepared according to a procedure similar to that described for Example 57.

[0745] Part B: tert-Butyl (1-((6-bromo-5-(difluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-yl)carbamate

[0746]

[0747] This compound was prepared using tert-butyl (1-hydroxy-2-methylpropan-2-yl)carbamate (0.9 g, 4.87 mmol) and 2-bromo-3-(difluoromethyl)-5-fluoropyridine (1.0 g, 4.42 mmol) (Example 33, Part A) and a clear liquid (0.3 g, 17.1%) was obtained. LC-MS (ESI+) m / z 395.3 [(M+H) + , calcd. C 15 H 21 BrF2N2O3m / z394.0].

[0748]

[0749] Part C: 1-((5-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine

[0750]

[0751] This compound was prepared using tert-butyl (1-((6-bromo-5-(difluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-yl)carbamate (100.0 mg, 0.25 mmol) (Example 63, Part B) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (130.6 mg, 0.38 mmol) to obtain an off-white powder (23.3 mg, 27.7%). 1 H NMR (500 MHz, MeOD) δ8.96 (d, 1H), 8.76 (s, 1H), 8.56 (d, 1H), 8.09 (s, 1H), 7.98 (s, 1H), 7.69 (t, 1H), 6.83-7.04 (m, 1H), 4.30 (s, 2H), 1.51 (s, 6H) LC-MS (ESI+)m / z333.5 [(M+H) + , calcd. C17H18F2N4Om / z332.1].

[0752]

[0753] Example 64: 1-((5-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine [1-((5-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]

[0754]

[0755] Example 64 was prepared as an intermediate according to a procedure similar to that described for Example 10 using tert-butyl (1-((6-bromo-5-(difluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-yl)carbamate (100.0 mg, 0.25 mmol) (Example 63, Part B) and 1H-pyrrolo[3,2-b]pyridine (29.8 mg, 0.25 mmol). After purification, hydrochloric acid (1.0 M EtOAc solution, 10 mL) was added, and the mixture was stirred at room temperature for deprotection of the tert-butoxy carbonyl group. The progress of the reaction was monitored by HPLC. After the reaction was completed, the product was extracted with EtOAc and 10% NaOH solution (aq.). The separated organic layer was washed with water and brine, dried over magnesium sulfate, and concentrated. The residue was washed with tetrahydrofuran and n-hexane to obtain an off-white powder (17.4 mg, 20.6%). 1 H NMR (500 MHz, MeOD) δ8.72 (d, 1H), 8.60 (d, 1H), 8.50 (d, 1H), 8.30 (d, 1H), 8.03 (d, 1H), 7.76-7.79 (m, 1H), 7.14 (d, 1H), 6.69-6.90 (m, 1H), 4.31 (s, 2H), 1.53 (m, 6H). LC-MS (ESI+)m / z333.5 [(M+H) + , calcd. C 17 H 18 F2N4Om / z332.1].

[0756]

[0757] Example 65: 1-(((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]

[0758]

[0759] Example 65 was prepared according to a procedure similar to that described for Example 57.

[0760] Part B: tert-Butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropyl)carbamate

[0761]

[0762] This compound was prepared using tert-butyl (1-(hydroxymethyl)cyclopropyl)carbamate (372.8 mg, 1.99 mmol) and 6-bromo-2-(difluoromethyl)-3-fluoropyridine (300.0 mg, 1.32 mmol) (Example 13, Part A) and an off-white powder (387.5 mg, 74.2%) was obtained. LC-MS (ESI+) m / z 393.1 [(M+H) + , calcd. C 15 H 19 BrF2N2O3m / z392.0].

[0763]

[0764] Part C: 1-(((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine

[0765]

[0766] This compound was prepared using tert-butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.25 mmol) (Example 65, Part B) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (131.3 mg, 0.38 mmol) to obtain an ivory powder (17.2 mg, 20.4%). 1 H NMR (500 MHz, MeOD) δ9.64 (d, 1H), 8.48 (d, 1H), 8.34 (s, 1H), 8.07 (d, 1H), 7.68-7.71 (m, 2H), 7.16-7.38 (m, 1H), 4.32 (s, 2H), 1.15-1.19 (m, 4H). LC-MS (ESI+)m / z331.3 [(M+H) + , calcd. C 17 H 16 F2N4Om / z330.1].

[0767]

[0768] Example 66: 1-(((2-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((2-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]

[0769]

[0770] Example 66 was prepared according to a procedure similar to that described for Example 57.

[0771] Part C: 1-(((2-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine

[0772]

[0773] This compound was prepared using tert-butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.25 mmol) (Example 65, Part B) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (112.2 mg, 294.2 mmol) to obtain an off-white powder (24.2 mg, 33.9%). 1 H NMR (500 MHz, MeOD) δ8.68 (s, 2H), 7.94 (d, 1H), 7.70 (d, 1H), 7.07-7.28 (m, 1H), 4.30 (s, 2H), 1.12-1.27 (m, 4H). LC-MS (ESI+)m / z000.0 [(M+H) + , calcd. C 13 H 14 F2N4Om / z280.1].

[0774]

[0775] Example 67: 1-(((2-(difluoromethyl)-6-(2H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((2-(difluoromethyl)-6-(2H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]

[0776]

[0777] Example 67 was prepared according to a procedure similar to that described for Example 8.

[0778] Part B: 1-(((2-(difluoromethyl)-6-(2H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine

[0779]

[0780] This compound was prepared using tert-butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.25 mmol) (Example 65, Part B) and 2-(tetrahydro-2H-pyran-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-1,2,3-triazole (106.4 mg, 0.38 mmol) to obtain an off-white powder (17.1 mg, 23.9%). 1 H NMR (500 MHz, MeOD) 8.42 (s, 1H), 8.13 (d, 1H), 7.72 (d, 1H), 7.06-7.28 (m, 1H), 4.31 (s, 2H), 1.12-1.22 (m, 4H). LC-MS (ESI+)m / z282.3 [(M+H) + , calcd. C 12 H 13 F2N5Om / z281.1].

[0781]

[0782] Example 68: 1-(((2-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((2-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]

[0783]

[0784] Example 68 was prepared according to a procedure similar to that described for Example 57.

[0785] Part C: 1-(((2-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine

[0786]

[0787] This compound was prepared using tert-butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.25 mmol) (Example 65, Part B) and tert-butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (138.1 mg, 0.38 mmol) to obtain a pale-yellow powder (34.1 mg, 38.5%). 1 H NMR (500 MHz, MeOD) δ9.10 (d, 1H), 8.43 (s, 1H), 8.27 (s, 1H), 7.98 (d, 1H), 7.64 (d, 1H), 7.12-7.34 (m, 1H), 4.28 (s, 2H), 1.11-1.18 (m, 4H). LC-MS (ESI+)m / z349.3 [(M+H) + , calcd. C 17 H 15 F3N4Om / z348.1].

[0788]

[0789] Example 69: 1-(((2-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((2-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]

[0790]

[0791] Example 69 was prepared according to a similar procedure as described for Example 64 using tert-butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.25 mmol) (Example 65, part B) and 1H-pyrrolo[3,2-b]pyridine (30.0 mg, 0.25 mmol) to obtain an off-white powder (15.4 mg, 18.3%). 1 H NMR (500 MHz, MeOD) δ9.54 (d, 1H), 8.70-8.74 (m, 2H), 8.04 (d, 1H), 7.95 (d, 1H), 7.84-7.86 (m, 1H), 7.21-7.43 (m, 1H), 7.14 (d, 1H), 4.38 (s, 2H), 1.15-1.22 (m, 4H). LC-MS (ESI+)m / z331.5 [(M+H) + , calcd. C 17 H 16 F2N4Om / z330.1].

[0792]

[0793] Example 70: 1-(((6-(1H-pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((6-(1H-pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]

[0794]

[0795] Example 70 was prepared according to a procedure similar to that described for Example 57.

[0796] Part B: tert-Butyl (1-(((6-bromo-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropyl)carbamate

[0797]

[0798] This compound was prepared using tert-butyl (1-(hydroxymethyl)cyclopropyl)carbamate (253.2 mg, 1.35 mmol) and 6-bromo-3-fluoro-2-(trifluoromethyl)pyridine (300.0 mg, 1.23 mmol) and obtained as an off-white powder (290.7 mg, 59.8%). LC-MS (ESI+) m / z 411.1 [(M+H) + , calcd. C15H18BrF3N2O3m / z410.0].

[0799]

[0800] Part C: 1-(((6-(1H-pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine

[0801]

[0802] This compound was prepared using tert-butyl (1-(((6-bromo-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.24 mmol) (Example 70, Part B) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (107.3 mg, 0.36 mmol) to obtain a pale-brown powder (38.2 mg, 52.6%). 1 H NMR (500 MHz, MeOD) 8.65 (br, 2H), 8.06 (d, 1H), 7.83 (d, 1H), 4.37 (s, 2H), 1.15-1.23 (m, 4H). LC-MS (ESI+)m / z299.3 [(M+H) + , calcd. C 13 H 13 F3N4Om / z298.1].

[0803]

[0804] Example 71: 1-((5-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine [1-((5-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]

[0805]

[0806] Example 71 was prepared according to a procedure similar to that described for Example 57.

[0807] Part B: tert-Butyl (1-(((6-bromo-5-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropyl)carbamate

[0808]

[0809] This compound was prepared using tert-butyl (1-(hydroxymethyl)cyclopropyl)carbamate (273.4 mg, 1.46 mmol) and 2-bromo-3-(difluoromethyl)-5-fluoropyridine (300.0 mg, 1.33 mmol) (Example 33, Part A) and an off-white powder (253.1 mg, 48.4%) was obtained. LC-MS (ESI+) m / z 393.1 [(M+H) + , calcd. C 15 H 19 BrF2N2O3m / z392.0].

[0810]

[0811] Part C: 1-((5-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine

[0812]

[0813] This compound was prepared using tert-butyl (1-(((6-bromo-5-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.25 mmol) (Example 71, Part B) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (131.3 mg, 0.38 mmol) to obtain an off-white powder (33.9 mg, 40.3%). 1 H NMR (500 MHz, MeOD) δ8.96 (d, 1H), 8.68 (d, 1H), 8.54 (d, 1H), 7.93-7.96 (m, 2H), 7.65-7.68 (m, 1H), 6.82-7.04 (m, 1H), 4.31 (s, 2H), 1.12-1.19 (m, 4H). LC-MS (ESI+)m / z331.3 [(M+H) + , calcd. C 17 H 16 F2N4Om / z330.1].

[0814]

[0815] Example 72: 1-(((5-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((5-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]

[0816]

[0817] Example 72 was prepared according to a procedure similar to that described for Example 57.

[0818] Part C: 1-(((5-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine

[0819]

[0820] This compound was prepared using tert-butyl (1-(((6-bromo-5-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.25 mmol) (Example 71, Part B) and tert-butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (138.1 mg, 0.38 mmol) to obtain an off-white powder (35.7 mg, 40.3%). 1 H NMR (500 MHz, MeOD) δ8.64 (d, 1H), 8.26 (s, 1H), 8.01-8.05 (m, 2H), 7.78 (s, 1H), 6.77-6.99 (m, 1H), 4.38 (s, 2H), 1.12-1.20 (m, 4H). LC-MS (ESI+)m / z349.3 [(M+H) + , calcd. C 17 H 15 F3N4Om / z348.1].

[0821]

[0822] Example 73: 1-(((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine [1-(((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine]

[0823]

[0824] Example 73 was prepared according to a procedure similar to that described for Example 57.

[0825] Part B: tert-Butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutyl)carbamate

[0826]

[0827] This compound was prepared using tert-butyl (1-(hydroxymethyl)cyclobutyl)carbamate (489.8 mg, 2.43 mmol) and 2-bromo-3-(difluoromethyl)-5-fluoropyridine (500.0 mg, 2.21 mmol) (Example 13, Part A) and an off-white powder (677.6 mg, 75.2%) was obtained. LC-MS (ESI+) m / z 407.3 [(M+H) + , calcd. C 16 H 21 BrF2N2O3m / z406.0].

[0828]

[0829] Part C: 1-(((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine

[0830]

[0831] This compound was prepared using tert-butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutyl)carbamate (100.0 mg, 0.25 mmol) (Example 73, Part B) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (126.7 mg, 0.37 mmol) to obtain a pale-brown powder (34.6 mg, 40.9%). 1 H NMR (500 MHz, MeOD) δ9.65 (d, 1H), 8.50 (d, 1H), 8.37 (s, 1H), 8.12 (d, 1H), 7.81 (d, 1H), 7.69-7.72 (m, 1H), 7.12-7.33 (m, 1H), 4.44 (s, 2H), 2.36-2.48 (m, 4H), 2.09-2.14 (m, 2H). LC-MS (ESI+)m / z345.3 [(M+H) + , calcd. C 18 H 18 F2N4Om / z344.1].

[0832]

[0833] Example 74: 1-(((2-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine [1-(((2-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine]

[0834]

[0835] Example 74 was prepared according to a procedure similar to that described for Example 57.

[0836] Part C: 1-(((2-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine

[0837]

[0838] This compound was prepared using tert-butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutyl)carbamate (100.0 mg, 0.25 mmol) (Example 73, Part B) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (108.3 mg, 0.37 mmol) to obtain an ivory powder (30.7 mg, 42.4%). 1 H NMR (500 MHz, MeOD) δ8.70 (s, 2H), 7.98 (d, 1H), 7.82 (d, 1H), 7.02-7.24 (m, 1H), 4.43 (s, 2H), 2.35-2.47 (m, 4H), 2.07-2.12 (m, 2H). LC-MS (ESI+)m / z295.4 [(M+H) + , calcd. C 14 H 16 F2N4Om / z294.1].

[0839]

[0840] Example 75: 1-(((2-(difluoromethyl)-6-(2H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine [1-(((2-(difluoromethyl)-6-(2H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine]

[0841]

[0842] Example 75 was prepared according to a procedure similar to that described for Example 8.

[0843] Part B: 1-(((2-(difluoromethyl)-6-(2H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine

[0844]

[0845] This compound was prepared using (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutyl)carbamate (100.0 mg, 0.25 mmol) (Example 73, Part B) and 2-(tetrahydro-2H-pyran-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-1,2,3-triazole (102.8 mg, 0.37 mmol) to obtain a pale-yellow powder (36.6 mg, 50.4%). 1 H NMR (500 MHz, MeOD) δ8.54 (s, 1H), 8.19 (d, 1H), 7.85 (d, 1H), 7.03-7.24 (m, 1H), 4.44 (s, 2H), 2.35-2.45 (m, 4H), 2.08-2.12 (m, 2H). LC-MS (ESI+)m / z296.3 [(M+H) + , calcd. C 13 H 15 F2N5Om / z295.1].

[0846]

[0847] Example 76: 1-(((2-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine [1-(((2-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine]

[0848]

[0849] Example 76 was prepared according to a similar procedure as described for Example 64 using tert-butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutyl)carbamate (100.0 mg, 0.25 mmol) (Example 73, Part B) and 1H-pyrrolo[3,2-b]pyridine (29.0 mg, 0.25 mmol) to obtain an off-white powder (18.7 mg, 22.1%). 1 H NMR (500 MHz, MeOD) δ9.55 (d, 1H), 8.71-8.76 (m, 2H), 8.07-8.08 (m, 2H), 7.84-7.87 (m, 1H), 7.15-7.38 (m, 2H), 4.50 (s, 2H), 2.38-2.47 (m, 4H), 2.10-2.15 (m, 2H). LC-MS (ESI+)m / z345.4 [(M+H) + , calcd. C 18 H 18 F2N4Om / z344.1].

[0850]

[0851] Example 77: 1-(((6-(1H-pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine [1-(((6-(1H-pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine]

[0852]

[0853] Example 77 was prepared according to a procedure similar to that described for Example 57.

[0854] Part B: tert-Butyl (1-(((6-bromo-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutyl)carbamate

[0855]

[0856] This compound was prepared using tert-butyl (1-(hydroxymethyl)cyclobutyl)carbamate (453.7 mg, 2.25 mmol) and 6-bromo-3-fluoro-2-(trifluoromethyl)pyridine (500.0 mg, 2.05 mmol) and obtained as an off-white powder (734.8 mg, 84.3%). LC-MS (ESI+) m / z 425.1 [(M+H) + , calcd. C 16 H 20 BrF3N2O3m / z424.0].

[0857]

[0858] Part C: 1-(((6-(1H-pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine

[0859]

[0860] This compound was prepared using tert-butyl (1-(((6-bromo-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutyl)carbamate (100.0 mg, 0.24 mmol) (Example 77, Part B) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (103.7 mg, 0.35 mmol) to obtain a pale-brown powder (42.6 mg, 58.0%). 1H NMR (500 MHz, MeOD) 8.63 (br, 2H), 8.07 (d, 1H), 7.90 (d, 1H), 4.43 (s, 2H), 2.40-2.44 (m, 4H), 2.07-2.10 (m, 2H). LC-MS (ESI+)m / z313.4 [(M+H) + , calcd. C 14 H 15 F3N4Om / z312.1].

[0861]

[0862] Example 78: 1-(((6-(2H-1,2,3-triazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine [1-(((6-(2H-1,2,3-triazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine]

[0863]

[0864] Example 78 was prepared according to a procedure similar to that described for Example 8.

[0865] Part B: 1-(((6-(2H-1,2,3-triazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine

[0866]

[0867] This compound was prepared using tert-butyl (1-(((6-bromo-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutyl)carbamate (100.0 mg, 0.24 mmol) (Example 77, Part B) and 2-(tetrahydro-2H-pyran-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-1,2,3-triazole (98.4 mg, 0.35 mmol) to obtain a pale-yellow powder (58.4 mg, 79.2%). 1H NMR (500 MHz, MeOD) 8.44 (s, 1H), 8.28 (d, 1H), 7.95 (d, 1H), 4.45 (s, 2H), 2.41-2.44 (m, 4H), 2.07-2.10 (m, 2H). LC-MS (ESI+)m / z314.3 [(M+H) + , calcd. C 13 H 14 F3N5Om / z313.1].

[0868]

[0869] Example 79: 1-((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-ol [1-((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-ol]

[0870]

[0871] Example 79 was prepared according to a procedure similar to that described for Example 13.

[0872] Part B: 1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-ol

[0873]

[0874] This compound was prepared using 2-methylpropane-1,2-diol (219.3 mg, 2.43 mmol) and 6-bromo-2-(difluoromethyl)-3-fluoropyridine (500.0 mg, 2.21 mmol) (Example 13, Part A) and a clear liquid (295.7 mg, 45.1%) was obtained. LC-MS (ESI+) m / z 296.1 [(M+H) + , calcd. C 10 H 12 BrF2NO2m / z295.0].

[0875]

[0876] Part C: 1-((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-ol

[0877]

[0878] This compound was prepared using 1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-ol (100.0 mg, 0.34 mmol) (Example 79, Part B) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (174.3 mg, 0.51 mmol) to obtain a pale-yellow powder (43.3 mg, 38.4%). 1 H NMR (500 MHz, MeOD) δ9.58 (d, 1H), 8.44 (d, 1H), 8.25 (s, 1H), 7.98 (d, 1H), 7.61-7.65 (m, 2H), 7.02-7.24 (m, 1H), 3.92 (s, 2H), 1.33 (s, 6H). LC-MS (ESI+)m / z334.4 [(M+H) + , calcd. C 17 H 17 F2N3O2m / z333.1].

[0879]

[0880] Example 80: 1-((2-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2-methylpropan-2-ol [1-((2-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2-methylpropan-2-ol]

[0881]

[0882] Example 80 was prepared according to a similar procedure as described for Example 10 using 1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-ol (100.0 mg, 0.34 mmol) (Example 79, Part B), 1H-pyrrolo[3,2-b]pyridine (39.9 mg, 0.34 mmol) to obtain an ivory powder (31.2 mg, 27.7%). 1 H NMR (500 MHz, MeOD) δ8.87 (d, 1H), 8.40 (d, 1H), 8.18 (d, 1H), 7.78 (s, 2H), 7.30-7.33 (m, 1H), 7.03-7.25 (m, 1H), 6.84 (d, 1H), 3.95 (s, 2H), 1.35 (m, 6H). LC-MS (ESI+)m / z334.4 [(M+H) + , calcd. C 17 H 17 F2N3O2m / z333.1].

[0883]

[0884] Example 81: (S)-1-(4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2,4-dimethylpentan-2-amine [(S)-1-(4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2,4-dimethylpentan-2-amine]

[0885]

[0886] Part A: (S)-1-(4-iodophenoxy)-2,4-dimethylpentan-2-amine

[0887]

[0888] A solution of 1-fluoro-4-iodobenzene (200.0 mg, 0.90 mmol), (S)-2-amino-2,4-dimethylpentan-1-ol (130.0 mg, 0.99 mmol), and potassium tert-butoxide (505.4 mg, 4.50 mmol) in tetrahydrofuran (8 mL) was irradiated in a microwave at 120°C for 1 h. The progress of the reaction was monitored by TLC and HPLC. After the reaction was completed, the mixture was diluted with EtOAc and water. The separated organic layer was washed with water and brine, dried over magnesium sulfate, and concentrated. The residue was purified by MPLC (silica gel, eluted with CH2Cl2: MeOH = 10:1, v / v) to give a pale-yellow liquid. LC-MS (ESI+) m / z 334.1 [(M+H) + , calcd. C 13 H 20 INOm / z333.0].

[0889]

[0890] Example 81 was prepared according to a procedure similar to that described for Example 13.

[0891] Part C: (S)-1-(4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2,4-dimethylpentan-2-amine

[0892]

[0893] This compound was prepared using (S)-1-(4-iodophenoxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 81, Part A) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (154.9 mg, 0.45 mmol) to obtain a dark-ivory powder (41.3 mg, 42.5%). 1H NMR (500 MHz, MeOD) δ8.92 (d, 1H), 8.48 (d, 1H), 7.90 (s, 1H), 7.63-7.70 (m, 3H), 7.21 (d, 2H), 4.07-4.18 (m, 2H), 1.83-1.87 (m, 2H), 1.68-1.70 (m, 1H), 1.50 (s, 3H), 1.07 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+)m / z324.2 [(M+H) + , calcd. C 20 H 25 N3Om / z323.1].

[0894]

[0895] Example 82: (S)-1-((6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [(S)-1-((6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]

[0896]

[0897] Part A: tert-Butyl (S)-(1-((6-iodopyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate

[0898]

[0899] Diisopropyl azodicarboxylate (6.2 mL, 31.67 mmol) was added dropwise to a solution of 6-iodopyridin-3-ol (3.5 g, 15.84 mmol), tert-butyl (S)-(1-hydroxy-4-methylpentan-2-yl)carbamate (8.6 g, 39.59 mmol), and triphenyl phosphine (8.3 g, 31.67 mmol) in tetrahydrofuran (100 mL). The reaction mixture was stirred at room temperature for 2 h. The progress of the reaction was monitored by TLC and HPLC. After the reaction was completed, water and EtOAc were added. The separated organic layer was washed with water and brine, dried over magnesium sulfate, and concentrated. The residue was purified by MPLC (silica gel, eluted with EtOAc inn-hexane from 0 to 20%), and an off-white powder (5.7 g, 85.6%) was obtained. LC-MS (ESI+) m / z 421.3 [(M+H) + , calcd. C 16 H 25 IN2O3m / z420.0].

[0900]

[0901] Example 82 was prepared according to a procedure similar to that described for Example 57.

[0902] Part C: (S)-1-((6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine

[0903]

[0904] This compound was prepared using tert-butyl (S)-(1-((6-iodopyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 82, Part A) and tert-butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (129.2 mg, 0.36 mmol) to obtain a pale-yellow powder (15.6 mg, 19.9%).1 H NMR (500 MHz, MeOD) 8.39-8.44 (m, 2H), 8.16 (s, 1H), 7.99 (s, 1H), 7.76 (d, 1H), 7.49-7.52 (m, 1H), 4.30-4.35 (m, 1H), 4.11-4.15 (m, 1H), 3.64-3.66 (m, 1H), 1.79-1.84 (m, 1H), 1.58-1.69 (m, 2H), 1.03 (t, 6H). LC-MS (ESI+)m / z329.2 [(M+H) + , calcd. C 18 H 21 FN4Om / z328.1].

[0905]

[0906] Example 83: (S)-1-((6-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [(S)-1-((6-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]

[0907]

[0908] Example 83 was prepared according to a procedure similar to that described for Example 57.

[0909] Part C: (S)-1-((6-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine

[0910]

[0911] This compound was prepared using tert-butyl (S)-(1-((6-iodopyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 82, Part A) and tert-butyl 4-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (133.5 mg, 0.36 mmol) to obtain an ivory powder (17.8 mg, 21.9%). 1 H NMR (500 MHz, MeOD) δ8.23 (m, 1H), 8.12 (d, 1H), 7.80 (d, 1H), 7.48-7.51 (m, 2H), 6.74 (d, 1H), 4.24-4.26 (m, 1H), 4.06-4.09 (m, 1H), 3.95 (s, 3H), 3.55-3.57 (m, 1H), 1.79-1.82 (m, 1H), 1.55-1.63 (m, 2H), 1.00 (t, 6H). LC-MS (ESI+)m / z341.7 [(M+H) + , calcd. C 19 H 24 N4O2m / z340.1].

[0912]

[0913] Example 84: (S)-1-((6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [(S)-1-((6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]

[0914]

[0915] Example 84 was prepared according to a procedure similar to that described for Example 57.

[0916] Part C: (S)-1-((6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine

[0917]

[0918] This compound was prepared using tert-butyl (S)-(1-((6-iodopyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 82, Part A) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (133.5 mg, 0.36 mmol) to obtain an ivory powder (23.3 mg, 37.6%). 1 H NMR (500 MHz, MeOD) δ8.28 (d, 1H), 8.09 (b, 2H), 7.68 (d, 1H), 7.51-7.53 (m, 1H), 4.33-4.35 (m, 1H), 4.15-4.18 (m, 1H), 3.69-3.71 (m, 1H), 1.79-1.82 (m, 1H), 1.64-1.72 (m, 2H), 1.02 (t, 6H). LC-MS (ESI+)m / z261.6 [(M+H) + , calcd. C 14 H 20 N4Om / z260.1].

[0919]

[0920] Example 85: (S)-1-((6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [(S)-1-((6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]

[0921]

[0922] Example 85 was prepared according to a procedure similar to that described for Example 57.

[0923] Part C: (S)-1-((6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine

[0924]

[0925] This compound was prepared using tert-butyl (S)-(1-((6-iodopyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 82, Part A) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (122.8 mg, 0.36 mmol) to obtain an ivory powder (16.7 mg, 22.6%). 1 H NMR (500 MHz, MeOD) δ9.03 (d, 1H), 8.52-8.58 (m, 2H), 8.37 (s, 1H), 8.25 (d, 1H), 8.13 (d, 1H), 7.62-7.64 (m, 1H), 4.51-4.53 (m, 1H), 4.34-4.37 (m, 1H), 3.78-3.79 (m, 1H), 1.76-1.86 (m, 1H), 1.67-1.76 (m, 2H), 1.05 (d, 3H), 1.04 (d, 3H). LC-MS (ESI+)m / z311.5 [(M+H) + , calcd. C 18 H 22 N4Om / z310.1].

[0926]

[0927] Example 86: (S)-1-((6-(4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [(S)-1-((6-(4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]

[0928]

[0929] Example 86 was prepared according to a procedure similar to that described for Example 57.

[0930] Part C: (S)-1-((6-(4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine

[0931]

[0932] This compound was prepared using tert-butyl (S)-(1-((6-iodopyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 82, Part A) and tert-butyl 4-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (129.2 mg, 0.36 mmol) to obtain a brown powder (36.5 mg, 46.7%). 1 H NMR (500 MHz, MeOD) δ8.30 (d, 1H), 8.21-8.23 (m, 1H), 7.76 (d, 2H), 7.50-7.52 (m, 1H), 6.93-6.96 (m, 1H), 4.18-4.21 (m, 1H), 3.99-4.03 (m, 1H), 3.44-3.49 (m, 1H), 1.77-1.83 (m, 1H), 1.49-1.58 (m, 2H), 0.97-1.00 (m, 6H). LC-MS (ESI+)m / z329.6 [(M+H) + , calcd. C 18 H 21 FN4Om / z328.1].

[0933]

[0934] Example 87: (S)-1-((6-(6-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [(S)-1-((6-(6-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]

[0935]

[0936] Example 87 was prepared according to a procedure similar to that described for Example 57.

[0937] Part C: (S)-1-((6-(6-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine

[0938]

[0939] This compound was prepared using tert-butyl (S)-(1-((6-iodopyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 82, Part A) and tert-butyl 6-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (129.2 mg, 0.36 mmol) to obtain a pale-brown powder (28.7 mg, 36.7%). 1 H NMR (500 MHz, MeOD) δ8.50-8.53 (m, 2H), 8.25-8.30 (m, 2H), 8.17 (s, 1H), 6.98 (d, 1H), 4.51-4.54 (m, 1H), 4.34-4.37 (m, 1H), 3.77-3.79 (m, 1H), 1.74-1.85 (m, 1H), 1.63-1.71 (m, 2H), 1.02-1.04 (m, 6H). LC-MS (ESI+)m / z329.4 [(M+H) + , calcd. C 18 H 21 FN4Om / z328.1].

[0940]

[0941] Example 88: (S)-1-((6-(6-fluoro-1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [(S)-1-((6-(6-fluoro-1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]

[0942]

[0943] Example 88 was prepared according to a similar procedure as described for Example 64 using tert-butyl (S)-(1-((6-iodopyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 82, Part A) and 6-fluoro-1H-pyrrolo[3,2-b]pyridine (32.3 mg, 0.24 mmol) to obtain a pale-brown powder (27.6 mg, 35.3%). 1 H NMR (500 MHz, MeOD) δ9.33 (d, 1H), 8.89 (d, 1H), 8.67 (d, 1H), 8.44 (d, 1H), 7.77-7.85 (m, 2H), 7.11 (d, 1H), 4.24-4.44 (m, 2H), 3.74-3.75 (m, 1H), 1.65-1.83 (m, 3H), 1.03-1.05 (m, 6H). LC-MS (ESI+)m / z329.3 [(M+H) + , calcd. C 18 H 21 FN4Om / z328.1].

[0944]

[0945] Example 89: (S)-1-((6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [(S)-1-((6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]

[0946]

[0947] Example 89 was prepared according to a similar procedure as described for Example 64 using tert-butyl (S)-(1-((6-iodopyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 82, Part A) and 1H-pyrrolo[3,2-b]pyridine (28.1 mg, 0.24 mmol) to obtain an ivory powder (13.5 mg, 18.2%). 1H NMR (500 MHz, MeOD) δ9.39 (d, 1H), 8.66-8.70 (m, 2H), 8.45 (d, 1H), 7.79-7.86 (m, 3H), 7.12 (d, 1H), 4.25-4.45 (m, 2H), 3.73-3.77 (m, 1H), 1.66-1.84 (m, 3H), 1.03-1.05 (m, 6H). LC-MS (ESI+)m / z311.6 [(M+H) + , calcd. C 18 H 22 N4Om / z310.1].

[0948]

[0949] Example 90: (S)-1-((6-(1H-pyrrolo[2,3-c]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [(S)-1-((6-(1H-pyrrolo[2,3-c]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]

[0950]

[0951] Example 90 was prepared according to a similar procedure as described for Example 64 using tert-butyl (S)-(1-((6-iodopyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 82, Part A) and 1H-pyrrolo[2,3-c]pyridine (28.1 mg, 0.24 mmol) to obtain an ivory powder (17.3 mg, 23.4%). 1 H NMR (500 MHz, MeOD) δ9.99 (s, 1H), 8.76 (d, 1H), 8.45 (d, 1H), 8.38 (d, 1H), 8.24 (d, 1H), 7.91 (d, 1H), 7.79-7.81 (m, 1H), 7.21 (d, 1H), 4.25-4.45 (m, 2H), 3.75-3.77 (m, 1H), 1.66-1.84 (m, 3H), 1.03-1.05 (m, 6H). LC-MS (ESI+)m / z311.3 [(M+H)+ , calcd. C 18 H 22 N4Om / z310.1].

[0952]

[0953] Example 91: (S)-1-((6-(1H-pyrrolo[2,3-b]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [(S)-1-((6-(1H-pyrrolo[2,3-b]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]

[0954]

[0955] Example 91 was prepared according to a similar procedure as described for Example 64 using tert-butyl (S)-(1-((6-iodopyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 82, Part A) and 1H-pyrrolo[2,3-b]pyridine (28.1 mg, 0.24 mmol) to obtain an ivory powder (19.8 mg, 23.4%). 1 H NMR (500 MHz, MeOD) δ8.82 (d, 1H), 8.61 (d, 1H), 8.51 (d, 1H), 8.46 (d, 1H), 7.99 (d, 1H), 7.83-7.85 (m, 1H), 7.75-7.79 (m, 1H), 7.16 (d, 1H), 4.11-4.31 (m, 2H), 3.75-3.76 (m, 1H), 1.61-1.74 (m, 3H), 1.02-1.04 (m, 6H). LC-MS (ESI+)m / z311.1 [(M+H) + , calcd. C 18 H 22 N4Om / z310.1].

[0956]

[0957] Example 92: (S)-1-((6-(1H-pyrrolo[3,2-c]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [(S)-1-((6-(1H-pyrrolo[3,2-c]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]

[0958]

[0959] Example 92 was prepared according to a similar procedure as described for Example 64 using tert-butyl (S)-(1-((6-iodopyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 82, Part A) and 1H-pyrrolo[3,2-c]pyridine (28.1 mg, 0.24 mmol) to obtain an ivory powder (15.6 mg, 21.1%). 1 H NMR (500 MHz, MeOD) δ9.25 (s, 1H), 8.73 (d, 1H), 8.45-8.47 (m, 2H), 8.35 (d, 1H), 7.78-7.85 (m, 2H), 7.28 (d, 1H), 4.24-4.44 (m, 2H), 3.74-3.76 (m, 1H), 1.64-1.83 (m, 3H), 1.02-1.04 (m, 6H). LC-MS (ESI+)m / z311.2 [(M+H) + , calcd. C 18 H 22 N4Om / z310.1].

[0960]

[0961] Example 93: (S)-1-(4-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-4-methylpentan-2-amine [(S)-1-(4-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-4-methylpentan-2-amine]

[0962]

[0963] Example 93 was prepared according to a procedure similar to that described for Example 82.

[0964] Part A: tert-Butyl (S)-(1-(4-iodophenoxy)-4-methylpentan-2-yl)carbamate

[0965]

[0966] This compound was prepared using 4-iodophenol (100.0 mg, 0.45 mmol) and tert-butyl (S)-(1-hydroxy-4-methylpentan-2-yl)carbamate (198.0 mg, 0.91 mmol) at 100 o It was prepared in C and ivory powder (134.3 mg, 70.4%) was obtained. LC-MS (ESI+) m / z 420.1 [(M+H) + , calcd. C 17 H 26 INO3m / z419.0].

[0967]

[0968] Example 93 was prepared according to a procedure similar to that described for Example 57.

[0969] Part C: (S)-1-(4-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-4-methylpentan-2-amine

[0970]

[0971] This compound was prepared using tert-butyl (S)-(1-(4-iodophenoxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mol) (Example 93, Part A) and tert-butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (129.5 mg, 0.36 mmol) to obtain an ivory powder (15.3 mg, 19.5%). 1H NMR (500 MHz, MeOD) δ8.13 (s, 1H), 7.94-7.97 (m, 1H), 7.62 (s, 1H), 7.54 (d, 2H), 7.04 (d, 2H), 3.99-4.02 (m, 1H), 3.80-3.83 (m, 1H), 3.25-3.28 (m, 1H), 1.78-1.82 (m, 1H), 1.37-1.43 (m, 2H), 0.98 (d, 3H), 0.96 (d, 3H). LC-MS (ESI+)m / z328.4 [(M+H) + , calcd. C 19 H 22 FN3Om / z327.1].

[0972]

[0973] Example 94: (S)-1-(4-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(trifluoromethyl)phenoxy)-4-methylpentan-2-amine [(S)-1-(4-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(trifluoromethyl)phenoxy)-4-methylpentan-2-amine]

[0974]

[0975] Example 94 was prepared according to a procedure similar to that described for Example 82.

[0976] Part A: tert-Butyl (S)-(1-(4-bromo-2-(trifluoromethyl)phenoxy)-4-methylpentan-2-yl)carbamate

[0977]

[0978] This compound was prepared using 4-bromo-2-(trifluoromethyl)phenol (300.0 mg, 1.24 mmol) and tert-butyl (S)-(1-hydroxy-4-methylpentan-2-yl)carbamate (217.3 mg, 2.49 mmol) and obtained as an ivory powder (293.3 mg, 53.5%). LC-MS (ESI+) m / z 440.4 [(M+H) +, calcd. C 18 H 25 BrF3NO3m / z439.0].

[0979]

[0980] Example 94 was prepared according to a procedure similar to that described for Example 57.

[0981] Part C: (S)-1-(4-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(trifluoromethyl)phenoxy)-4-methylpentan-2-amine

[0982]

[0983] This compound was prepared using tert-butyl (S)-(1-(4-bromo-2-(trifluoromethyl)phenoxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.23 mmol) (Example 94, Part A) and tert-butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (123.4 mg, 0.34 mmol) to obtain a yellow powder (32.6 mg, 36.3%). 1 H NMR (500 MHz, MeOD) δ8.30-8.38 (m, 2H), 7.86-7.92 (m, 3H), 7.38 (d, 1H), 4.23-4.40 (m, 2H), 3.70-3.72 (m, 1H), 1.75-1.80 (m, 2H), 1.61-1.64 (m, 1H),0.99-1.01 (m, 6H). LC-MS (ESI+)m / z396.3 [(M+H) + , calcd. C 20 H 21 F4N3Om / z395.1].

[0984]

[0985] Example 95: 1-(((6-(2H-1,2,3-triazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((6-(2H-1,2,3-triazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]

[0986]

[0987] Example 95 was prepared according to a procedure similar to that described for Example 8.

[0988] Part B: 1-(((6-(2H-1,2,3-triazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine

[0989]

[0990] This compound was prepared using tert-butyl (1-(((6-bromo-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.24 mol) (Example 70, Part B) and tert-butyl 2-(tetrahydro-2H-pyran-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-1,2,3-triazole (101.8 mg, 0.36 mmol) to obtain an ivory powder (44.4 mg, 61.0%). 1 H NMR (500 MHz, MeOD) 8.37 (s, 1H), 8.23 ​​(d, 1H), 7.83 (d, 1H), 4.36 (s, 2H), 1.13-1.20 (m, 4H). LC-MS (ESI+)m / z300.2 [(M+H) + , calcd. C 12 H 12 F3N5Om / z299.0].

[0991]

[0992] Example 96: 1-(((6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]

[0993]

[0994] Example 96 was prepared according to a procedure similar to that described for Example 82.

[0995] Part A: tert-Butyl (1-(((6-bromopyridin-3-yl)oxy)methyl)cyclopropyl)carbamate

[0996]

[0997] This compound was prepared using 6-bromopyridin-3-ol (100.0 mg, 0.57 mol) and tert-butyl (1-(hydroxymethyl)cyclopropyl)carbamate (215.2 mg, 1.15 mmol) and obtained as an off-white powder (54.0 mg, 27.3%). LC-MS (ESI+) m / z 343.6 [(M+H) + , calcd. C 14 H 19 BrN2O3m / z342.0].

[0998]

[0999] Example 96 was prepared according to a procedure similar to that described for Example 57.

[1000] Part C: 1-(((6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine

[1001]

[1002] This compound was prepared using tert-butyl (1-(((6-bromopyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.29 mol) (Example 96, Part A) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (150.4 mg, 0.44 mmol) to obtain a brown powder (30.6 mg, 37.4%). 1 H NMR (500 MHz, MeOD) δ9.07 (d, 1H), 8.59 (d, 2H), 8.44 (s, 1H), 8.24-8.34 (m, 2H), 7.71-7.73 (m, 1H), 4.44 (s, 2H), 1.15-1.20 (m, 4H). LC-MS (ESI+)m / z281.3 [(M+H) + , calcd. C 16 H 16 N4Om / z280.1].

[1003]

[1004] Example 97: 1-(((6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]

[1005]

[1006] Example 97 was prepared according to a procedure similar to that described for Example 57.

[1007] Part C: 1-(((6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine

[1008]

[1009] This compound was prepared using tert-butyl (1-(((6-bromopyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.29 mmol) (Example 96, Part A) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (128.5 mg, 0.44 mmol) to obtain a pale-yellow powder (20.2 mg, 30.1%). 1 H NMR (500 MHz, MeOD) 8.39-8.43 (m, 3H), 8.21-8.27 (m, 2H), 4.40 (s, 2H), 1.13-1.19 (m, 4H). LC-MS (ESI+)m / z231.4 [(M+H) + , calcd. C 12 H 14 N4Om / z230.1].

[1010]

[1011] Example 98: 1-(((6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]

[1012]

[1013] Example 98 was prepared according to a similar procedure as described for Example 64 using tert-butyl (1-(((6-bromopyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.29 mmol) (Example 96, Part A) and 1H-pyrrolo[3,2-b]pyridine (34.4 mg, 0.29 mmol) to obtain an ivory powder (15.1 mg, 18.4%). 1H NMR (500 MHz, MeOD) δ9.35 (d, 1H), 8.65-8.71 (m, 2H), 7.91-7.95 (m, 1H), 7.82-7.85 (m, 1H), 7.75 (d, 1H), 7.13 (d, 1H), 4.40 (s, 2H), 1.13-1.19 (m, 4H). LC-MS (ESI+)m / z281.3 [(M+H) + , calcd. C 16 H 16 N4Om / z280.1].

[1014]

[1015] Example 99: 1-(((2-fluoro-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((2-fluoro-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]

[1016]

[1017] Example 99 was prepared according to a procedure similar to that described for Example 82.

[1018] Part A: tert-Butyl (1-(((6-bromo-2-fluoropyridin-3-yl)oxy)methyl)cyclopropyl)carbamate

[1019]

[1020] This compound was prepared using 6-bromo-2-fluoropyridin-3-ol (1.0 g, 5.21 mmol) and tert-butyl (1-(hydroxymethyl)cyclopropyl)carbamate (1.9 g, 10.42 mmol) and an off-white powder (0.72 g, 38.2%) was obtained. LC-MS (ESI+) m / z 361.5 [(M+H) + , calcd C 14 H 18 BrFN2O3m / z360.0].

[1021]

[1022] Example 99 was prepared according to a procedure similar to that described for Example 57.

[1023] Part C: 1-(((2-fluoro-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine

[1024]

[1025] This compound was prepared using tert-butyl (1-(((6-bromopyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.28 mol) (Example 96, Part A) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (142.9 mg, 0.42 mmol) to obtain a yellow powder (28.5 mg, 34.5%). 1 H NMR (500 MHz, MeOD) δ9.46 (d, 1H), 8.48 (d, 1H), 8.29 (s, 1H), 7.80 (d, 1H), 7.66-7.81 (m, 2H), 4.29 (s, 2H), 1.11-1.19 (m, 4H). LC-MS (ESI+)m / z299.5 [(M+H) + , calcd C 16 H 15 FN4Om / z298.1].

[1026]

[1027] Example 100: 1-(((2-fluoro-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((2-fluoro-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]

[1028]

[1029]

[1030] Example 100 was prepared according to a procedure similar to that described for Example 57.

[1031] Part C: 1-(((2-Fluoro-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine

[1032]

[1033] This compound was prepared using (1-(((6-bromo-2-fluoropyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.28 mmol) (Example 99, Part A) and tert-butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (150.4 mg, 0.42 mmol) to obtain a pale-yellow powder (23.9 mg, 27.9%). 1 H NMR (500 MHz, MeOD) δ8.87-8.89 (m, 1H), 8.40 (t, 1H), 8.21 (s, 1H), 7.70 (d, 1H), 7.60-7.64 (m, 1H), 4.23 (s, 2H), 1.07-1.15 (m, 4H). LC-MS (ESI+)m / z317.3 [(M+H) + , calcd C 16 H 14 F2N4Om / z316.1].

[1034]

[1035] Example 101: 1-(((2-fluoro-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((2-fluoro-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]

[1036]

[1037] Example 101 was prepared according to a procedure similar to that described for Example 64 using tert-butyl (1-(((6-bromopyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.28 mmol) (Example 99, Part A) and 1H-pyrrolo[3,2-b]pyridine (32.7 mg, 0.28 mmol) to obtain an off-white powder (10.1 mg, 12.2%). 1 H NMR (500 MHz, MeOD) δ9.35 (d, 1H), 8.65-8.71 (m, 2H), 7.91-7.95 (m, 1H), 7.82-7.85 (m, 1H), 7.75 (d, 1H), 7.13 (d, 1H), 4.35 (s, 2H), 1.14-1.21 (m, 4H). LC-MS (ESI+)m / z299.3 [(M+H) + , calcd. C 16 H 15 FN4Om / z298.1].

[1038]

[1039] Example 102: 1-(((4-fluoro-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((4-fluoro-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]

[1040]

[1041] Example 102 was prepared according to a procedure similar to that described for Example 82.

[1042] Part A: tert-Butyl (1-(((6-bromo-4-fluoropyridin-3-yl)oxy)methyl)cyclopropyl)carbamate

[1043]

[1044] This compound was prepared using 6-bromo-4-fluoropyridin-3-ol (0.5 g, 2.60 mmol) and tert-butyl (1-(hydroxymethyl)cyclopropyl)carbamate (0.7 g, 3.91 mmol) and obtained as an off-white powder (0.89 g, 94.9%). LC-MS (ESI+) m / z 361.4 [(M+H) + , calcd C 14 H 18 BrFN2O3m / z360.0].

[1045]

[1046] Example 102 was prepared according to a procedure similar to that described for Example 57.

[1047] Part C: 1-(((4-fluoro-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine

[1048]

[1049] This compound was prepared using tert-butyl (1-(((6-bromo-4-fluoropyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.28 mmol) (Example 102, Part A) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (142.9 mg, 0.42 mmol) to obtain an off-white powder (36.7 mg, 44.4%). 1 H NMR (500 MHz, MeOD) δ9.23 (d, 1H), 8.76 (d, 1H), 8.62 (d, 1H), 8.49 (s, 1H), 8.25 (d, 1H), 7.76-7.79 (m, 1H), 4.51 (s, 2H), 1.17-1.23 (m, 4H). LC-MS (ESI+)m / z299.6 [(M+H) + , calcd C 16 H 15 FN4Om / z298.1].

[1050]

[1051] Example 103: 1-(((4-fluoro-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((4-fluoro-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]

[1052]

[1053] Example 103 was prepared according to a procedure similar to that described for Example 57.

[1054] Part C: 1-(((4-fluoro-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine

[1055]

[1056] This compound was prepared using tert-butyl (1-(((6-bromo-4-fluoropyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.28 mmol) (Example 102, Part A) and tert-butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (150.4 mg, 0.42 mmol) to obtain a pale-brown powder (44.4 mg, 50.7%). 1 H NMR (500 MHz, MeOD) 8.66 (d, 1H), 8.41 (s, 1H), 8.35-8.37 (m, 2H), 8.24 (d, 1H), 4.50 (s, 2H), 1.16-1.24 (m, 4H). LC-MS (ESI+)m / z317.3 [(M+H) + , calcd C 16 H 14 F2N4Om / z316.1].

[1057]

[1058] Example 104: 1-(((5-fluoro-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((5-fluoro-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]

[1059]

[1060] Example 104 was prepared according to a procedure similar to that described for Example 82.

[1061] Part A: tert-Butyl (1-(((6-bromo-5-fluoropyridin-3-yl)oxy)methyl)cyclopropyl)carbamate

[1062]

[1063] This compound was prepared using 6-bromo-5-fluoropyridin-3-ol (500.0 mg, 2.60 mmol) and tert-butyl (1-(hydroxymethyl)cyclopropyl)carbamate (975.2 mg, 5.21 mmol) and obtained as an off-white powder (650.0 mg, 69.1%). LC-MS (ESI+) m / z 361.5 [(M+H) + , calcd C 14 H 18 BrFN2O3m / z360.0].

[1064]

[1065] Example 104 was prepared according to a procedure similar to that described for Example 57.

[1066] Part C: 1-(((5-fluoro-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine

[1067]

[1068] This compound was prepared using tert-butyl (1-(((6-bromo-5-fluoropyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.28 mmol) (Example 104, Part A) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (000.0 mg, 0.6 mmol) to obtain a pale-yellow powder (24.8 mg, 30.0%). 1 H NMR (500 MHz, MeOD) δ9.56 (d, 1H), 8.54 (d, 1H), 8.44 (d, 1H), 8.22 (d, 1H), 7.70-7.72 (m, 1H), 7.57-7.60 (m, 1H), 4.32 (s, 2H), 1.11-1.20 (m, 4H). LC-MS (ESI+)m / z299.6 [(M+H) + , calcd C 16 H 15 FN4Om / z298.1].

[1069]

[1070] Example 105: 1-(((5-fluoro-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((5-fluoro-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]

[1071]

[1072] Example 105 was prepared according to a procedure similar to that described for Example 57.

[1073] Part C: 1-(((5-fluoro-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine

[1074]

[1075] This compound was prepared using tert-butyl tert-butyl (1-(((6-bromo-5-fluoropyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.28 mmol) (Example 104, Part A) and tert-butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (150.4 mg, 0.42 mmol) to obtain a brown powder (16.1 mg, 18.3%). 1 H NMR (500 MHz, MeOD) 8.88 (d, 1H), 8.50 (s, 1H), 8.42 (d, 1H), 8.22 (d, 1H), 7.74-7.77 (m, 1H), 4.33 (s, 2H), 1.11-1.19 (m, 4H). LC-MS (ESI+)m / z317.1 [(M+H) + , calcd C 16 H 14 F2N4Om / z316.1].

[1076]

[1077] Example 106: 1-(((6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine [1-(((6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine]

[1078]

[1079] Example 106 was prepared according to a procedure similar to that described for Example 82.

[1080] Part A: tert-Butyl (1-(((6-iodopyridin-3-yl)oxy)methyl)cyclobutyl)carbamate

[1081]

[1082] This compound was prepared using 6-iodopyridin-3-ol (500.0 mg, 2.26 mmol) and tert-butyl (1-(hydroxymethyl)cyclobutyl)carbamate (910.7 mg, 4.52 mmol) and obtained as an off-white powder (103.5 mg, 11.3%). LC-MS (ESI+) m / z 405.4 [(M+H) + , calcd. C 15 H 21 IN2O3m / z404.2].

[1083]

[1084] Example 106 was prepared according to a procedure similar to that described for Example 57.

[1085] Part C: 1-(((6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine

[1086]

[1087] This compound was prepared using tert-butyl (1-(((6-iodopyridin-3-yl)oxy)methyl)cyclobutyl)carbamate (100.0 mg, 0.25 mmol) (Example 106, Part A) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (127.7 mg, 0.37 mmol) to obtain a brown powder (11.8 mg, 16.2%). 1 H NMR (500 MHz, MeOD) δ9.01 (d, 1H), 8.49 (d, 1H), 8.43 (d, 1H), 8.20 (s, 1H), 8.04 (d, 1H), 7.82 (d, 1H), 7.49-7.51 (m, 1H), 4.44 (s, 2H), 2.37-2.43 (m, 4H), 2.09-2.14 (m, 2H). LC-MS (ESI+)m / z000.0 [(M+H) + , calcd. C 17 H 18 N4Om / z294.1].

[1088]

[1089] Example 107: 1-(2-(difluoromethyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine [1-(2-(difluoromethyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine]

[1090]

[1091] Part A: tert-Butyl (1-(4-bromo-2-(difluoromethyl)phenoxy)-2-methylpropan-2-yl)carbamate

[1092]

[1093] Potassium carbonate (1.5 g, 11.06 mmol) was added to a solution of tert-butyl (1-hydroxy-2-methylpropan-2-yl)carbamate (2.0 g, 11.06 mmol) and 4-bromo-2-(difluoromethyl)-1-fluorobenzene (1.0 g, 4.42 mmol) in dimethyl sulfoxide (4 mL). The reaction mixture was stirred at 120 o C was irradiated in a microwave for 5 h. The progress of the reaction was monitored by TLC and HPLC. After the reaction was completed, the mixture was diluted with EtOAc and water. The separated organic layer was washed with water and brine, dried over magnesium sulfate, and concentrated. The residue was purified by MPLC (silica gel, eluted with 0–20% EtOAc in n-hexane) to obtain an off-white powder (0.24 g, 13.9%). LC-MS (ESI+) m / z 394.6 [(M+H) + , calcd. C 16 H 22 BrF2NO3m / z393.0].

[1094]

[1095] Example 107 was prepared according to a procedure similar to that described for Example 57.

[1096] Part C: 1-(2-(difluoromethyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine

[1097]

[1098] This compound was prepared using tert-butyl (1-(4-bromo-2-(difluoromethyl)phenoxy)-2-methylpropan-2-yl)carbamate (100.0 mg, 0.25 mmol) (Example 107, Part A) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (130.9 mg, 0.38 mmol) to obtain a pale-yellow powder (19.8 mg, 23.5%). 1 H NMR (500 MHz, MeOD) δ8.87 (d, 1H), 8.48 (d, 1H), 7.96 (s, 1H), 7.87 (d, 2H), 7.64-7.66 (m, 1H), 7.15-7.37 (m, 2H), 4.17 (s, 2H), 1.51 (s, 6H). LC-MS (ESI+)m / z332.6 [(M+H) + , calcd. C 18 H 19 F2N3Om / z331.1].

[1099]

[1100] Example 108:N 1 -(2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)-2-methylpropane-1,2-diamine [N 1 -(2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)-2-methylpropane-1,2-diamine]

[1101]

[1102] Example 108 was prepared according to a procedure similar to that described for Example 107.

[1103] Part A: tert-Butyl (1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)amino)-2-methylpropan-2-yl)carbamate

[1104]

[1105] This compound was prepared using tert-butyl (1-amino-2-methylpropan-2-yl)carbamate (1.2 g, 6.64 mmol) and 6-bromo-2-(difluoromethyl)-3-fluoropyridine (1.0 g, 4.42 mmol) (Example 13, Part A) and an off-white powder (0.52 g, 29.8%) was obtained. LC-MS (ESI+) m / z 394.3 [(M+H) + , calcd. C 15 H 22 BrF2N3O2m / z393.0].

[1106]

[1107] Example 108 was prepared according to a procedure similar to that described for Example 57.

[1108] C Part:N 1 -(2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)-2-methylpropane-1,2-diamine

[1109]

[1110] This compound was prepared using tert-butyl (1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)amino)-2-methylpropan-2-yl)carbamate (100.0 mg, 0.25 mmol) (Example 108, Part A) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (130.9 mg, 0.38 mmol) to obtain a pale-yellow powder (36.9 mg, 43.9%). 1H NMR (500 MHz, MeOD) δ9.60 (d, 1H), 8.45 (d, 1H), 8.21 (s, 1H), 7.90 (d, 1H), 7.64-7.67 (m, 1H), 7.52 (d, 1H), 6.90-7.12 (m, 1H), 3.49 (s, 2H), 1.41 (s, 6H). LC-MS (ESI+)m / z332.4 [(M+H) + , calcd. C 17 H 19 F2N5m / z331.1].

[1111]

[1112] Example 109:N 1 -(2-(Difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)-2-methylpropane-1,2-diamine [N 1 -(2-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)-2-methylpropane-1,2-diamine]

[1113]

[1114] Example 109 was prepared according to a similar procedure as described for Example 64 using tert-butyl (1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)amino)-2-methylpropan-2-yl)carbamate (100.0 mg, 0.25 mmol) (Example 108, Part A) and 1H-pyrrolo[3,2-b]pyridine (29.9 mg, 0.25 mmol) to obtain a pale-yellow powder (19.6 mg, 23.3%). 1 H NMR (500 MHz, MeOD) δ8.63 (d, 1H), 8.37 (d, 1H), 8.07 (d, 1H), 7.63 (d, 1H), 7.56 (d, 1H), 7.25-7.28 (m, 1H), 6.78-6.801 (m, 2H), 3.27 (s, 2H), 1.25 (m, 6H). LC-MS (ESI+)m / z332.3 [(M+H) +, calcd. C 17 H 19 F2N5m / z331.1].

[1115]

[1116] Example 110:N 1 -(6-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(trifluoromethyl)pyridin-3-yl)-2-methylpropane-1,2-diamine [N 1 -(6-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(trifluoromethyl)pyridin-3-yl)-2-methylpropane-1,2-diamine]

[1117]

[1118] Example 110 was prepared according to a procedure similar to that described for Example 107.

[1119] Part A: tert-Butyl (1-((6-bromo-2-(trifluoromethyl)pyridin-3-yl)amino)-2-methylpropan-2-yl)carbamate

[1120]

[1121] This compound was prepared using 6-bromo-3-fluoro-2-(trifluoromethyl)pyridine (500.0 mg, 2.05 mmol) and tert-butyl (1-amino-2-methylpropan-2-yl)carbamate (578.7 mg, 3.07 mmol) and obtained as an off-white powder (574.6 mg, 76.2%). LC-MS (ESI+) m / z 412.3 [(M+H) + , calcd. C 15 H 21 BrF3N3O2m / z411.0].

[1122]

[1123] Example 110 was prepared according to a procedure similar to that described for Example 57.

[1124] C Part:N 1-(6-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(trifluoromethyl)pyridin-3-yl)-2-methylpropane-1,2-diamine

[1125]

[1126] This compound was prepared using tert-butyl (1-((6-bromo-2-(trifluoromethyl)pyridin-3-yl)amino)-2-methylpropan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 110, Part A) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (125.2 mg, 0.36 mmol) to obtain a yellow powder (33.1 mg, 39.0%). 1 H NMR (500 MHz, MeOD) δ9.54 (d, 1H), 8.45 (d, 1H), 8.25 (s, 1H), 7.98 (d, 1H), 7.60-7.67 (m, 2H), 3.52 (s, 2H), 1.39 (s, 6H). LC-MS (ESI+)m / z350.6 [(M+H) + , calcd. C 17 H 18 F3N5m / z349.1].

[1127]

[1128] Example 111:N 1 -(2-(difluoromethyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenyl)-2-methylpropane-1,2-diamine [N 1 -(2-(difluoromethyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenyl)-2-methylpropane-1,2-diamine]

[1129]

[1130] Example 111 was prepared according to a procedure similar to that described for Example 107.

[1131] Part A: tert-Butyl (1-((4-bromo-2-(difluoromethyl)phenyl)amino)-2-methylpropan-2-yl)carbamate

[1132]

[1133] This compound was prepared using 4-bromo-2-(difluoromethyl)-1-fluorobenzene (1.0 g, 4.42 mmol) and tert-butyl (1-amino-2-methylpropan-2-yl)carbamate (1.6 g, 8.85 mmol) and obtained as a pale-yellow powder (146.7 mg, 8.4%). LC-MS (ESI+) m / z 393.2 [(M+H) + , calcd. C 16 H 23 BrF2N2O2m / z392.0].

[1134]

[1135] Example 111 was prepared according to a procedure similar to that described for Example 57.

[1136] C Part:N 1 -(2-(difluoromethyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenyl)-2-methylpropane-1,2-diamine

[1137]

[1138] This compound was prepared using tert-butyl (1-((4-bromo-2-(difluoromethyl)phenyl)amino)-2-methylpropan-2-yl)carbamate (100.0 mg, 0.25 mmol) (Example 111, Part A) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (131.2 mg, 0.38 mmol) to obtain a yellow powder (13.5 mg, 16.0%). 1H NMR (500 MHz, MeOD) δ8.23-8.27 (m, 2H), 7.66-7.69 (m, 2H), 7.57 (s, 1H), 7.17-7.20 (m, 1H), 6.87-7.09 (m, 2H), 3.45 (s, 2H), 1.43 (s, 6H). LC-MS (ESI+)m / z331.6 [(M+H) + , calcd. C 18 H 20 F2N4m / z330.1].

[1139]

[1140] Example 112: N-((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-amine [N-((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-amine]

[1141]

[1142] Example 112 was prepared according to a procedure similar to that described for Example 107.

[1143] Part A: tert-Butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)amino)methyl)cyclopropyl)carbamate

[1144]

[1145] This compound was prepared using 6-bromo-2-(difluoromethyl)-3-fluoropyridine (500.0 mg, 2.21 mmol) (Example 13, Part A) and tert-butyl (1-(aminomethyl)cyclopropyl)carbamate (618.1 mg, 3.32 mmol) and a pale-yellow powder (340.5 mg, 35.0%) was obtained. LC-MS (ESI+) m / z 392.1 [(M+H) + , calcd. C 15 H 20BrF2N3O2m / z391.0].

[1146]

[1147] Example 112 was prepared according to a procedure similar to that described for Example 57.

[1148] Part C: N-((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-amine

[1149]

[1150] This compound was prepared using tert-butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)amino)methyl)cyclopropyl)carbamate (100.0 mg, 0.25 mmol) (Example 112, Part A) and tert-butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (138.5 mg, 0.38 mmol) to obtain a pale-orange powder (33.4 mg, 37.7%). 1 H NMR (500 MHz, MeOD) δ9.05-9.07 (m, 1H), 8.48 (t, 1H), 8.23 ​​(s, 1H), 7.92 (d, 1H), 7.54 (d, 1H), 6.96-7.17 (m, 1H), 3.62 (s, 2H), 1.01-1.03 (m, 4H). LC-MS (ESI+)m / z348.3 [(M+H) + , calcd. C 17 H 16 F3N5m / z347.1].

[1151]

[1152] Example 113: N-((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-amine [N-((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-amine]

[1153]

[1154] Example 113 was prepared according to a procedure similar to that described for Example 57.

[1155] Part C: N-((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-amine

[1156]

[1157] This compound was prepared using tert-butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)amino)methyl)cyclopropyl)carbamate (100.0 mg, 0.25 mmol) (Example 112, Part A) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (112.4 mg, 0.38 mmol) to obtain a yellow powder (30.5 mg, 42.8%). 1 H NMR (500 MHz, MeOD) δ8.53 (s, 2H), 7.82 (d, 1H), 7.53 (d, 1H), 6.80-7.02 (m, 1H), 3.60 (s, 2H), 0.95-1.02 (m, 4H). LC-MS (ESI+)m / z280.1 [(M+H) + , calcd. C 13 H 15 F2N5m / z279.1].

[1158]

[1159] Example 114: N-((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-amine [N-((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-amine]

[1160]

[1161] Example 114 was prepared according to a procedure similar to that described for Example 57.

[1162] Part C: N-((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-amine

[1163]

[1164] This compound was prepared using tert-butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)amino)methyl)cyclopropyl)carbamate (100.0 mg, 0.25 mmol) (Example 112, Part A) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (131.6 mg, 0.38 mmol) to obtain an ivory powder (19.3 mg, 22.9%). 1 H NMR (500 MHz, MeOD) δ9.56 (d, 1H), 8.43 (d, 1H), 8.19 (s, 1H), 7.89 (d, 1H), 7.61-7.63 (m, 1H), 7.43 (d, 1H), 6.87-7.08 (m, 1H), ,3.59 (s, 2H), 0.97-1.03 (m, 4H). LC-MS (ESI+)m / z330.5 [(M+H) + , calcd. C 17 H 17 F2N5m / z329.1].

[1165]

[1166] Example 115: N-((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-amine [N-((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-amine]

[1167]

[1168] Example 115 was prepared according to a similar procedure as described for Example 64 using tert-butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)amino)methyl)cyclopropyl)carbamate (100.0 mg, 0.25 mmol) (Example 112, Part A) and 1H-pyrrolo[3,2-b]pyridine (30.1 mg, 0.25 mmol) to obtain a yellow powder (18.5 mg, 22.0%). 1 H NMR (500 MHz, MeOD) δ9.37 (d, 1H), 8.60-8.67 (m, 2H), 7.76-7.85 (m, 2H), 7.63 (d, 1H), 6.89-7.10 (m, 2H), 3.63 (s, 2H), 1.03 (s, 4H). LC-MS (ESI+)m / z330.4 [(M+H) + , calcd. C 17 H 17 F2N5m / z329.1].

[1169]

[1170] Example 116: N-((1-aminocyclopropyl)methyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-amine [N-((1-aminocyclopropyl)methyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-amine]

[1171]

[1172] Example 116 was prepared according to a procedure similar to that described for Example 107.

[1173] Part A: tert-Butyl (1-(((6-bromopyridin-3-yl)amino)methyl)cyclopropyl)carbamate

[1174]

[1175] This compound was prepared using 2-bromo-5-fluoropyridine (1.0 g, 5.68 mmol) and tert-butyl (1-(aminomethyl)cyclopropyl)carbamate (2.1 g, 11.3 mmol) and obtained as an off-white powder (213.8 mg, 10.9%). LC-MS (ESI+) m / z 342.6 [(M+H) + , calcd. C 14 H 20 BrN3O2m / z341.0].

[1176]

[1177] Example 116 was prepared according to a procedure similar to that described for Example 57.

[1178] Part C: N-((1-aminocyclopropyl)methyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-amine

[1179]

[1180] This compound was prepared using tert-butyl (1-(((6-bromopyridin-3-yl)amino)methyl)cyclopropyl)carbamate (100.0 mg, 0.29 mmol) (Example 116, Part A) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (150.8 mg, 0.44 mmol) to obtain a yellow powder (25.4 mg, 31.1%). 1 H NMR (500 MHz, MeOD) δ8.84 (d, 1H), 8.54 (d, 1H), 8.28 (s, 1H), 8.12-8.15 (m, 2H), 7.95-9.97 (m, 1H), 7.61-7.64 (m, 1H). 3.60 (s, 2H), 1.02-1.09 (m, 4H). LC-MS (ESI+)m / z280.3 [(M+H) + , calcd. C 16 H 17 N5m / z279.1].

[1181]

[1182] Example 117: N-((1-aminocyclopropyl)methyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-amine [N-((1-aminocyclopropyl)methyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-amine]

[1183]

[1184] Example 117 was prepared according to a procedure similar to that described for Example 57.

[1185] Part C: N-((1-aminocyclopropyl)methyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-amine

[1186]

[1187] This compound was prepared using tert-butyl (1-(((6-bromopyridin-3-yl)amino)methyl)cyclopropyl)carbamate (100.0 mg, 0.29 mmol) (Example 116, Part A) and tert-butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (158.7 mg, 0.44 mmol) to obtain a yellow powder (16.8 mg, 19.3%). 1 H NMR (500 MHz, MeOD) δ8.30 (s, 1H), 8.15-8.06 (m, 2H), 8.03-8.08 (m, 2H), 7.91-7.93 (m, 1H), 3.57 (s, 2H), 1.01-1.08 (m, 4H). LC-MS (ESI+)m / z298.2 [(M+H) + , calcd. C 16 H 16 FN5m / z297.1].

[1188]

[1189] Example 118: N-((1-aminocyclopropyl)methyl)-4-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-amine [N-((1-aminocyclopropyl)methyl)-4-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-amine]

[1190]

[1191] Example 118 was prepared according to a procedure similar to that described for Example 107.

[1192] Part A: tert-Butyl (1-(((6-bromo-4-(difluoromethyl)pyridin-3-yl)amino)methyl)cyclopropyl)carbamate

[1193]

[1194] This compound was prepared using 2-bromo-4-(difluoromethyl)-5-fluoropyridine (0.5 g, 2.21 mmol) (Example 30, Part A) and tert-butyl (1-(aminomethyl)cyclopropyl)carbamate (1.0 g, 5.53 mmol) and obtained as a yellow powder (351.3 mg, 40.4%). LC-MS (ESI+) m / z 392.3 [(M+H) + , calcd. C 15 H 20 BrF2N3O2m / z391.0].

[1195]

[1196] Example 118 was prepared according to a procedure similar to that described for Example 57.

[1197] Part C: N-((1-aminocyclopropyl)methyl)-4-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-amine

[1198]

[1199] This compound was prepared using tert-butyl (1-(((6-bromo-4-(difluoromethyl)pyridin-3-yl)amino)methyl)cyclopropyl)carbamate (100.0 mg, 0.25 mmol) (Example 118, Part A) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (131.6 mg, 0.38 mmol) to obtain a yellow powder (32.2 mg, 38.3%). 1 H NMR (500 MHz, MeOD) δ9.06 (d, 1H), 8.62 (d, 1H), 8.49 (s, 1H), 8.41 (s, 1H), 8.26 (s, 1H), 7.74-7.77 (m, 1H), 7.17-7.92 (m, 1H), 3.79 (s, 2H), 1.08-1.10 (m, 4H). LC-MS (ESI+)m / z330.2 [(M+H) + , calcd. C 17 H 17 F2N5m / z329.1].

[1200]

[1201] Example 119: N-((1-aminocyclopropyl)methyl)-5-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-amine [N-((1-aminocyclopropyl)methyl)-5-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-amine]

[1202]

[1203] Example 119 was prepared according to a procedure similar to that described for Example 107.

[1204] Part A: tert-Butyl (1-(((6-bromo-5-(difluoromethyl)pyridin-3-yl)amino)methyl)cyclopropyl)carbamate

[1205]

[1206] This compound was prepared using 2-bromo-3-(difluoromethyl)-5-fluoropyridine (1.0 g, 4.42 mmol) (Example 33, Part A) and tert-butyl (1-(aminomethyl)cyclopropyl)carbamate (2.0 g, 11.0 mmol) and obtained as an ivory powder (264.5 mg, 15.2%). LC-MS (ESI+) m / z 392.4 [(M+H) + , calcd. C 15 H 20 BrF2N3O2m / z391.0].

[1207]

[1208] Example 119 was prepared according to a procedure similar to that described for Example 57.

[1209] Part C: N-((1-aminocyclopropyl)methyl)-5-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-amine

[1210]

[1211] This compound was prepared using tert-butyl (1-(((6-bromo-5-(difluoromethyl)pyridin-3-yl)amino)methyl)cyclopropyl)carbamate (100.0 mg, 0.25 mmol) (Example 119, Part A) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (131.6 mg, 0.38 mmol) to obtain an ivory powder (35.0 mg, 41.6%). 1 H NMR (500 MHz, MeOD) δ8.69-8.71 (m, 1H), 8.60 (d, 1H), 8.45 (s, 1H), 8.09-8.12 (m, 2H), 7.66-7.70 (m, 1H), 6.74-6.96 (m, 1H), 3.70 (s, 2H), 1.08-1.12 (m, 4H). LC-MS (ESI+)m / z330.4 [(M+H) + , calcd. C 17 H17 F2N5m / z329.1].

[1212]

[1213] Example 120: 1-((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)amino)-2-methylpropan-2-ol [1-((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)amino)-2-methylpropan-2-ol]

[1214]

[1215] Example 120 was prepared according to a procedure similar to that described for Example 107.

[1216] Part A: 1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)amino)-2-methylpropan-2-ol

[1217]

[1218] This compound was prepared using 6-bromo-2-(difluoromethyl)-3-fluoropyridine (1.0 g, 4.42 mmol) (Example 13, Part A) and 1-amino-2-methylpropan-2-ol (0.6 mL, 6.64 mmol) to obtain a pale-yellow liquid (700.0 mg, 53.6%). LC-MS (ESI+) m / z 296.4 [(M+H) + , calcd. C 10 H 13 BrF2N2Om / z294.0].

[1219]

[1220] Example 120 was prepared according to a procedure similar to that described for Example 13.

[1221] Part C: 1-((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)amino)-2-methylpropan-2-ol

[1222]

[1223] This compound was prepared using 1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)amino)-2-methylpropan-2-ol (100.0 mg, 0.34 mmol) (Example 120, Part A) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (174.9 mg, 0.51 mmol) and a yellow powder (30.6 mg, 27.1%) was obtained. 1 H NMR (500 MHz, MeOD) δ9.56 (d, 1H), 8.43 (d, 1H), 8.14 (s, 1H), 7.82 (d, 1H), 7.62-7.65 (m, 1H), 7.34 (d, 1H), 6.81-7.03 (m, 1H), 3.19 (s, 2H), 1.29 (s, 6H). LC-MS (ESI+)m / z333.3 [(M+H) + , calcd. C 17 H 18 F2N4Om / z332.1].

[1224]

[1225] Example 121: 1-((2-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)amino)-2-methylpropan-2-ol [1-((2-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)amino)-2-methylpropan-2-ol]

[1226]

[1227] Example 121 was prepared according to a similar procedure as described for Example 10 using 1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)amino)-2-methylpropan-2-ol (100.0 mg, 0.34 mmol) (Example 120, Part A) and 1H-pyrrolo[3,2-b]pyridine (40.3 mg, 0.34 mmol) to obtain a yellow powder (29.6 mg, 26.2%).1 H NMR (500 MHz, MeOD) δ8.59 (d, 1H), 8.36 (d, 1H), 8.05 (d, 1H), 7.59 (d, 1H), 7.47 (d, 1H), 7.25-7.28 (m, 1H), 6.73-6.94 (m, 2H), 3.19 (s, 2H), 1.29 (m, 6H). LC-MS (ESI+)m / z333.6 [(M+H) + , calcd. C 17 H 18 F2N4Om / z332.1].

[1228]

[1229] Example 122: 1-(2-chloro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine [1-(2-chloro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine]

[1230]

[1231] Part A: tert-Butyl (1-(4-bromo-2-chlorophenoxy)-2-methylpropan-2-yl)carbamate

[1232]

[1233] Potassium carbonate (0.8 g, 5.78 mmol) was added to a solution of 4-bromo-2-chlorophenol (0.6 g, 2.89 mmol) and tert-butyl 4,4-dimethyl-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide (1.1 g, 4.34 mmol) in N,N-dimethylformamide (5 mL). The reaction mixture was stirred at 100 oC was irradiated in a microwave for 1.5 h. The progress of the reaction was monitored by TLC and HPLC. After the reaction was completed, the mixture was diluted with EtOAc and water. The separated organic layer was washed with water and brine, dried over magnesium sulfate, and concentrated. The residue was purified by MPLC (silica gel, eluted with 0–20% EtOAc in n-hexane) to obtain an off-white powder. LC-MS (ESI+) m / z 378.6 [(M+H) + , calcd. C 15 H 21 BrClNO3m / z377.0].

[1234]

[1235] Example 122 was prepared according to a procedure similar to that described for Example 57.

[1236] Part C: 1-(2-chloro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine

[1237]

[1238] This compound was prepared using tert-butyl (1-(4-bromo-2-chlorophenoxy)-2-methylpropan-2-yl)carbamate (100.0 mg, 0.26 mmol) (Example 122, Part A) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (136.3 mg, 0.40 mmol) to obtain a pale-yellow powder (30.5 mg, 36.5%). 1 H NMR (500 MHz, MeOD) δ8.90 (d, 1H), 8.48 (d, 1H), 7.95 (s, 1H), 7.78 (d, 1H), 7.63-7.67 (m, 2H), 7.30 (d, 1H), 4.14 (s, 2H), 1.52 (s, 6H). LC-MS (ESI+)m / z316.3 [(M+H) + , calcd. C 17 H 18 ClN3Om / z315.1].

[1239]

[1240] Example 123: 1-(2-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine [1-(2-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine]

[1241]

[1242] Example 123 was prepared according to a procedure similar to that described for Example 122.

[1243] Part A: tert-Butyl (1-(4-bromo-2-fluorophenoxy)-2-methylpropan-2-yl)carbamate

[1244]

[1245] This compound was prepared using 4-bromo-2-fluorophenol (200.0 mg, 1.05 mmol) and tert-butyl 4,4-dimethyl-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide (394.7 mg, 1.57 mmol) and obtained as an off-white powder (309.0 mg, 54.9%). LC-MS (ESI+) m / z 362.2 [(M+H) + , calcd. C 15 H 21 BrFNO3m / z361.0].

[1246]

[1247] Example 123 was prepared according to a procedure similar to that described for Example 57.

[1248] Part C: 1-(2-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine

[1249]

[1250] This compound was prepared using tert-butyl (1-(4-bromo-2-fluorophenoxy)-2-methylpropan-2-yl)carbamate (100.0 mg, 0.28 mmol) (Example 123, Part A) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (142.5 mg, 0.41 mmol) to obtain a pale-yellow powder (31.3 mg, 37.8%). 1 H NMR (500 MHz, MeOD) δ8.91 (d, 1H), 8.48 (d, 1H), 7.94 (s, 1H), 7.62-7.65 (m, 1H), 7.50-7.56 (m, 2H), 7.30 (t, 1H), 4.13 (s, 2H), 1.49 (s, 6H). LC-MS (ESI+)m / z300.3 [(M+H) + , calcd. C 17 H 18 FN3Om / z299.1].

[1251]

[1252] Example 124: 1-(2,5-dichloro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine [1-(2,5-dichloro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine]

[1253]

[1254] Example 124 was prepared according to a procedure similar to that described for Example 122.

[1255] Part A: tert-Butyl (1-(4-bromo-2,5-dichlorophenoxy)-2-methylpropan-2-yl)carbamate

[1256]

[1257] This compound was prepared using 4-bromo-2,5-dichlorophenol (200.0 mg, 0.83 mmol) and tert-butyl 4,4-dimethyl-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide (311.6 mg, 1.24 mmol) and obtained as an off-white powder (179.0 mg, 52.4%). LC-MS (ESI+) m / z 412.1 [(M+H) + , calcd. C 15 H 20 BrCl2NO3m / z411.0].

[1258]

[1259] Example 124 was prepared according to a procedure similar to that described for Example 57.

[1260] Part C: 1-(2,5-dichloro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine

[1261]

[1262] Example 124 was prepared according to a similar procedure as described for Example 64 using tert-butyl (1-(4-bromo-2,5-dichlorophenoxy)-2-methylpropan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 124, Part A) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (131.5 mg, 0.36 mmol) to obtain an ivory powder (15.8 mg, 19.1%). 1 H NMR (500 MHz, MeOD) 8.59(d, 1H), 8.36(d, 1H), 8.05(d, 1H), 7.59(d, 2H), 7.47(d, 1H), 4.13(s, 2H), 1.49(s, 6H). LC-MS (ESI+)m / z350.3 [(M+H) + , calcd. C 17 H 17 Cl2N3Om / z349.0].

[1263]

[1264] Example 125: 2-methyl-1-(2-methyl-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)propan-2-amine [2-methyl-1-(2-methyl-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)propan-2-amine]

[1265]

[1266] Example 125 was prepared according to a procedure similar to that described for Example 122.

[1267] Part A: tert-Butyl (1-(4-bromo-2-methylphenoxy)-2-methylpropan-2-yl)carbamate

[1268]

[1269] This compound was prepared using 4-bromo-2-methylphenol (200.0 mg, 1.07 mmol) and tert-butyl 4,4-dimethyl-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide (403.0 mg, 1.60 mmol) and an off-white powder (213.3 mg, 55.6%) was obtained. LC-MS (ESI+) m / z 358.3 [(M+H) + , calcd. C 16 H 24 BrNO3m / z357.0].

[1270]

[1271] Example 125 was prepared according to a procedure similar to that described for Example 57.

[1272] Part C: 2-Methyl-1-(2-methyl-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)propan-2-amine

[1273]

[1274] This compound was prepared using tert-butyl (1-(4-bromo-2-methylphenoxy)-2-methylpropan-2-yl)carbamate (100.0 mg, 0.28 mmol) (Example 125, Part A) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (144.1 mg, 0.42 mmol) to obtain a yellow powder (27.5 mg, 33.7%). 1 H NMR (500 MHz, MeOD) δ8.88 (d, 1H), 8.44 (d, 1H), 7.85 (s, 1H), 7.60-7.63 (m, 1H), 7.51 (d, 2H), 7.08 (d, 1H), 4.05 (s, 2H), 2.37 (s, 3H), 1.50 (s, 6H). LC-MS (ESI+)m / z296.3 [(M+H) + , calcd. C 18 H 21 N3Om / z295.1].

[1275]

[1276] Example 126: 1-(2,6-difluoro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine [1-(2,6-difluoro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine]

[1277]

[1278] Example 126 was prepared according to a procedure similar to that described for Example 122.

[1279] Part A: tert-Butyl (1-(4-bromo-2,6-difluorophenoxy)-2-methylpropan-2-yl)carbamate

[1280]

[1281] This compound was prepared using 4-bromo-2,6-difluorophenol (200.0 mg, 0.96 mmol) and tert-butyl 4,4-dimethyl-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide (360.7 mg, 1.44 mmol) and obtained as an off-white powder (265.3 mg, 72.9%). LC-MS (ESI+) m / z 380.2 [(M+H) + , calcd. C 15 H 20 BrF2NO3m / z379.0].

[1282]

[1283] Example 126 was prepared according to a procedure similar to that described for Example 57.

[1284] Part C: 1-(2,6-difluoro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine

[1285]

[1286] This compound was prepared using tert-butyl (1-(4-bromo-2,6-difluorophenoxy)-2-methylpropan-2-yl)carbamate (100.0 mg, 0.26 mmol) (Example 126, Part A) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (135.7 mg, 0.39 mmol) to obtain a pale-yellow powder (28.6 mg, 34.2%). 1 H NMR (500 MHz, MeOD) 8.94 (d, 1H), 8.50 (d, 1H), 8.03 (s, 1H), 7.64-7.67 (m, 1H), 7.46 (d, 2H), 4.16 (s, 2H), 1.47 (s, 6H). LC-MS (ESI+)m / z318.5 [(M+H) + , calcd. C 17 H 17 F2N3Om / z317.1].

[1287]

[1288] Example 127: 1-(2,5-difluoro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine [1-(2,5-difluoro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine]

[1289]

[1290] Example 127 was prepared according to a procedure similar to that described for Example 122.

[1291] Part A: tert-Butyl (1-(4-bromo-2,5-difluorophenoxy)-2-methylpropan-2-yl)carbamate

[1292]

[1293] This compound was prepared using 4-bromo-2,5-difluorophenol (200.0 mg, 0.96 mmol) and tert-butyl 4,4-dimethyl-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide (360.7 mg, 1.44 mmol) and obtained as an off-white powder (182.6 mg, 50.1%). LC-MS (ESI+) m / z 380.3 [(M+H) + , calcd. C 15 H 20 BrF2NO3m / z379.0].

[1294]

[1295] Example 127 was prepared according to a procedure similar to that described for Example 57.

[1296] Part C: 1-(2,5-difluoro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine

[1297]

[1298] This compound was prepared using tert-butyl (1-(4-bromo-2,5-difluorophenoxy)-2-methylpropan-2-yl)carbamate (100.0 mg, 0.26 mmol) (Example 127, Part A) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (135.7 mg, 0.39 mmol) to obtain a pale-yellow powder (25.8 mg, 30.9%). 1 H NMR (500 MHz, MeOD) δ8.76 (d, 1H), 8.51 (d, 1H), 7.94 (s, 1H), 7.63-7.66 (m, 1H), 7.53-7.57 (m, 1H), 7.23-7.27 (m, 1H), 4.16 (s, 2H), 1.50 (s, 6H). LC-MS (ESI+)m / z318.3 [(M+H) + , calcd. C 17 H 17 F2N3Om / z317.1].

[1299]

[1300] Example 128: 5-fluoro-3-(4-(piperazin-1-yl)phenyl)-1H-pyrrolo[2,3-b]pyridine [5-fluoro-3-(4-(piperazin-1-yl)phenyl)-1H-pyrrolo[2,3-b]pyridine]

[1301]

[1302] Example 128 was prepared according to a procedure similar to that described for Example 13.

[1303] Part C: 5-Fluoro-3-(4-(piperazin-1-yl)phenyl)-1H-pyrrolo[2,3-b]pyridine

[1304]

[1305] This compound was prepared using 1-(4-bromophenyl)piperazine (100.0 mg, 0.41 mmol) and tert-butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (225.3 mg, 0.62 mmol) and an ivory powder (30.8 mg, 25.1%) was obtained. 1 H NMR (500 MHz, MeOD) δ8.33 (s, 1H), 8.26-8.28 (m, 1H), 7.78 (s, 1H), 7.63 (d, 2H), 7.18 (d, 2H), 3.42-3.50 (m, 8H). LC-MS (ESI+)m / z297.2 [(M+H) + , calcd. C 17 H 17 FN4m / z296.1].

[1306]

[1307] Example 129: 5-fluoro-3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrrolo[2,3-b]pyridine [5-fluoro-3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrrolo[2,3-b]pyridine]

[1308]

[1309] Example 129 was prepared according to a procedure similar to that described for Example 13.

[1310] Part C: 5-Fluoro-3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrrolo[2,3-b]pyridine

[1311]

[1312] This compound was prepared using 1-(4-bromophenyl)-4-methylpiperazine (100.0 mg, 0.39 mmol) and tert-butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (212.9 mg, 0.59 mmol) and an off-white powder (18.5 mg, 15.2%) was obtained. 1 H NMR (500 MHz, MeOD) δ8.15 (s, 1H), 7.99-8.01 (m, 1H), 7.64 (s, 1H), 7.56 (d, 2H), 7.10 (d, 2H), 3.26-3.28 (m, 4H), 2.67-2.69 (m, 4H), 2.39 (s, 3H). LC-MS (ESI+)m / z311.1 [(M+H) + , calcd. C 18 H 19 FN4m / z310.1].

[1313]

[1314] Example 130: 4-(4-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)phenyl)morpholine [4-(4-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)phenyl)morpholine]

[1315]

[1316] Example 130 was prepared according to a procedure similar to that described for Example 13.

[1317] Part C: 4-(4-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)phenyl)morpholine

[1318]

[1319] This compound was prepared using 4-(4-bromophenyl)morpholine (100.0 mg, 0.41 mmol) and tert-butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (224.4 mg, 0.62 mmol) and an ivory powder (20.1 mg, 16.4%) was obtained. 1 H NMR (500 MHz, MeOD) δ8.35 (s, 1H), 8.24-8.28 (m, 3H), 8.17-8.21 (m, 3H), 3.90-3.92 (m, 4H), 3.43-3.45 (m, 4H). LC-MS (ESI+)m / z298.3 [(M+H) + , calcd. C 17 H 16 FN3Om / z297.1].

[1320]

[1321] Example 131: 5-fluoro-3-(5-(piperazin-1-yl)pyridin-2-yl)-1H-pyrrolo[2,3-b]pyridine [5-fluoro-3-(5-(piperazin-1-yl)pyridin-2-yl)-1H-pyrrolo[2,3-b]pyridine]

[1322]

[1323] Example 131 was prepared according to a procedure similar to that described for Example 13.

[1324] Part C: 5-Fluoro-3-(5-(piperazin-1-yl)pyridin-2-yl)-1H-pyrrolo[2,3-b]pyridine

[1325]

[1326] This compound was prepared using 1-(6-bromopyridin-3-yl)piperazine (100.0 mg, 0.41 mmol) and tert-butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (224.4 mg, 0.62 mmol) and an ivory powder (24.6 mg, 20.0%) was obtained. 1 H NMR (500 MHz, MeOD) δ8.32 (s, 1H), 8.25-8.28 (m, 2H), 7.78 (s, 1H), 7.63 (d, 1H), 7.18 (d, 1H), 3.42-3.50 (m, 8H). LC-MS (ESI+)m / z298.3 [(M+H) + , calcd. C 16 H 16 FN5m / z297.1].

[1327]

[1328] Example 132: 5-fluoro-3-(5-(4-methylpiperazin-1-yl)pyridin-2-yl)-1H-pyrrolo[2,3-b]pyridine [5-fluoro-3-(5-(4-methylpiperazin-1-yl)pyridin-2-yl)-1H-pyrrolo[2,3-b]pyridine]

[1329]

[1330] Example 132 was prepared according to a procedure similar to that described for Example 13.

[1331] Part C: 5-Fluoro-3-(5-(4-methylpiperazin-1-yl)pyridin-2-yl)-1H-pyrrolo[2,3-b]pyridine

[1332]

[1333] This compound was prepared using 1-(6-bromopyridin-3-yl)-4-methylpiperazine (100.0 mg, 0.39 mmol) and tert-butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (212.1 mg, 0.59 mmol) and an ivory powder (34.8 mg, 28.6%) was obtained. 1 H NMR (500 MHz, MeOD) δ8.37-8.39 (m, 1H), 8.32 (d, 1H), 8.17 (s, 1H), 7.95 (s, 1H), 7.67 (d, 1H), 7.46-7.48 (m 1H), 3.31-3.33 (m, 4H), 2.67-2.69 (m, 4H), 2.39 (s, 3H). LC-MS (ESI+)m / z312.1 [(M+H) + , calcd. C 17 H 18 FN5m / z311.1].

[1334]

[1335] Example 133: 4-(6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)morpholine [4-(6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)morpholine]

[1336]

[1337] Example 133 was prepared according to a procedure similar to that described for Example 13.

[1338] Part C: 4-(6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)morpholine

[1339]

[1340] This compound was prepared using 4-(6-bromopyridin-3-yl)morpholine (100.0 mg, 0.41 mmol) and tert-butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (223.4 mg, 0.62 mmol) and an ivory powder (30.8 mg, 25.1%) was obtained. 1 H NMR (500 MHz, MeOD) δ8.37 (s, 1H), 8.25-8.26 (m, 2H), 8.17-8.21 (m, 3H), 3.90-3.92 (m, 4H), 3.43-3.45 (m, 4H). LC-MS (ESI+)m / z299.6 [(M+H) + , calcd. C 16 H 15 FN4Om / z298.1].

[1341]

[1342] Example 134: 4-(2-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)morpholine [4-(2-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)morpholine]

[1343]

[1344] Example 134 was prepared according to a procedure similar to that described for Example 13.

[1345] Part A: 3-Bromo-6-chloro-2-(difluoromethyl)pyridine

[1346]

[1347] This compound was prepared using 3-bromo-6-chloropicolinaldehyde (2.0 g, 9.07 mmol) and diethylaminosulfur trifluoride (2.6 mL, 18.14 mmol) and obtained as an off-white powder (2.0 g, 90.9%). LC-MS (ESI+) m / z 242.4 [(M+H) + , calcd. C6H3BrClF2Nm / z240.9].

[1348]

[1349] Part B: 4-(6-chloro-2-(difluoromethyl)pyridin-3-yl)morpholine

[1350]

[1351] A solution of 3-bromo-6-chloro-2-(difluoromethyl)pyridine (100.0 mg, 0.41 mmol) (Example 134, Part A), morpholine (35.9 mg, 0.41 mmol), tris(dibenzylideneacetone)dipalladium(0) (75.5 mg, 0.08 mmol), dicyclohexyl(2',6'-dimethoxy-[1,1'-biphenyl]-2-yl)phosphine (25.4 mg, 0.06 mmol), and sodium tert-butoxide (59.4 mg, 0.62 mmol) in toluene (5 mL) was irradiated in a microwave at 80 °C for 2.0 h. The progress of the reaction was monitored by TLC and HPLC. After the reaction was completed, the mixture was diluted with EtOAc and water. The separated organic layer was washed with water and brine, dried over magnesium sulfate, and concentrated. The residue was purified by MPLC (silica gel, eluted with 0-30% EtOAc in n-hexane) to obtain an ivory powder (18.7 mg, 18.2%). LC-MS (ESI+) m / z 249.6 [(M+H) + , calcd. C 10 H 11 ClF2N2Om / z248.0].

[1352]

[1353] Example 134 was prepared according to a procedure similar to that described for Example 13.

[1354] Part C: 4-(2-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)morpholine

[1355]

[1356] This compound was prepared using 4-(6-chloro-2-(difluoromethyl)pyridin-3-yl)morpholine (100.0 mg, 0.40 mmol) (Example 134, Part B) and tert-butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (218.5 mg, 0.60 mmol) to obtain a pale-brown powder (35.4 mg, 25.3%). 1 H NMR (500 MHz, MeOD) δ8.36-8.40 (m, 1H), 8.34 (d, 1H), 8.19 (s, 1H), 7.95 (s, 1H), 7.67 (d, 1H), 7.46-7.48 (m 1H), 3.90-3.92 (m, 4H), 3.43-3.45 (m, 4H). LC-MS (ESI+)m / z349.8 [(M+H) + , calcd. C 17 H 15 F3N4Om / z348.1].

[1357]

[1358] Example 135: 4-(2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)-2,2-dimethylmorpholine [4-(2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)-2,2-dimethylmorpholine]

[1359]

[1360] Example 135 was prepared according to a procedure similar to that described for Example 134.

[1361] Part B: 4-(6-chloro-2-(difluoromethyl)pyridin-3-yl)-2,2-dimethylmorpholine

[1362]

[1363] This compound was prepared using 3-bromo-6-chloro-2-(difluoromethyl)pyridine (1.0 g, 4.12 mmol) (Example 134, Part A) and 2,2-dimethylmorpholine (475.0 mg, 4.12 mmol) to obtain a light-brown liquid (150.4 mg, 13.1%). LC-MS (ESI+) m / z 277.1 [(M+H) + , calcd. C 12 H 15 ClF2N2Om / z276.0].

[1364]

[1365] Example 135 was prepared according to a procedure similar to that described for Example 13.

[1366] Part C: 4-(2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)-2,2-dimethylmorpholine

[1367]

[1368] This compound was prepared using 4-(6-chloro-2-(difluoromethyl)pyridin-3-yl)-2,2-dimethylmorpholine (100.0 mg, 0.36 mmol) (Example 135, Part B) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (181.1 mg, 0.54 mmol) to obtain a pale-red powder (26.8 mg, 20.7%). 1H NMR (500 MHz, MeOD) δ9.02 (d, 1H), 8.27 (d, 1H), 8.08 (s, 1H), 7.93 (d, 1H), 7.78 (d, 1H), 7.12-7.33 (m, 2H), 3.93-3.94 (m, 2H), 2.95-2.97 (m, 2H), 1.38 (s, 6H), 1.30-1.31 (m, 2H). LC-MS (ESI+)m / z359.5 [(M+H) + , calcd. C 19 H 20 F2N4Om / z358.1].

[1369]

[1370] Example 136: 3-(6-(difluoromethyl)-5-(3,3-dimethylpiperazin-1-yl)pyridin-2-yl)-1H-pyrrolo[2,3-b]pyridine [3-(6-(difluoromethyl)-5-(3,3-dimethylpiperazin-1-yl)pyridin-2-yl)-1H-pyrrolo[2,3-b]pyridine]

[1371]

[1372] Example 136 was prepared according to a procedure similar to that described for Example 134.

[1373] Part B: tert-Butyl 4-(6-chloro-2-(difluoromethyl)pyridin-3-yl)-2,2-dimethylpiperazine-1-carboxylate

[1374]

[1375] This compound was prepared using 3-bromo-6-chloro-2-(difluoromethyl)pyridine (300.0 mg, 1.24 mmol) (Example 134, Part A) and tert-butyl 2,2-dimethylpiperazine-1-carboxylate (265.1 mg, 1.24 mmol) and obtained as an ivory powder (115.3 mg, 24.7%). LC-MS (ESI+) m / z 376.2 [(M+H) + , calcd. C 17 H24 ClF2N3O2m / z375.1].

[1376]

[1377] Example 136 was prepared according to a procedure similar to that described for Example 57.

[1378] Part C: 3-(6-(difluoromethyl)-5-(3,3-dimethylpiperazin-1-yl)pyridin-2-yl)-1H-pyrrolo[2,3-b]pyridine

[1379]

[1380] This compound was prepared using tert-butyl 4-(6-chloro-2-(difluoromethyl)pyridin-3-yl)-2,2-dimethylpiperazine-1-carboxylate (100.0 mg, 0.27 mmol) (Example 136, Part B) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (137.3 mg, 0.40 mmol) to obtain a pale-yellow powder (17.0 mg, 18.5%). 1 H NMR (500 MHz, MeOD) δ9.46 (d, 1H), 8.45 (d, 1H), 8.34 (s, 1H), 8.08 (d, 1H), 7.93 (d, 1H), 7.56-7.58 (m, 1H), 7.13-7.35 (m, 1H), 3.68 (s, 2H), 3.50-3.51 (m, 2H), 3.25-3.27 (m, 2H), 1.58 (s, 6H). LC-MS (ESI+)m / z358.3 [(M+H) + , calcd. C 19 H 21 F2N5m / z357.1].

[1381]

[1382] Experimental Example 1. AAK1 Kinase Analysis

[1383] Assays were performed in U-bottom 384-well plates. The final assay volume was 30 μL, prepared by adding 15 μL of enzyme and substrate (fluorescent peptide (5-FAM)-Aha-KEEQSQITSQVTGQIGWR-NH2 and ATP) and test compounds to assay buffer (10 mM Tris-HCl pH 7.4, 10 mM MgCl2, 0.01% TWEEN20, and 1.0 mM DTT). The reaction was initiated by combining bacterially expressed GST-Xa-hAAK1 with the substrate and test compounds. The reaction was incubated at room temperature for 3 h and terminated by adding 60 μL of 35 mM EDTA buffer to each sample. The reaction was analyzed on a Caliper LabChip 3000 (Caliper, Hopkinton, MA) by electrophoretically separating the fluorescent substrate and phosphorylated products. Inhibition data were calculated by comparing EDTA-quenched control reactions with 100% inhibition and vehicle-only reactions with 0% inhibition. Final concentrations of reagents used in the assay were ATP, 22 μM; (5-FAM)-Aha-KEEQSQITSQVTGQIGWR-NH2, 1.5 μM; GST-Xa-hAAk1, 3.5 nM; and DMSO, 1.6%. The concentration required to inhibit 50% of kinase activity (IC 50 ) were generated to determine the IC. The compounds were dissolved in dimethyl sulfoxide (DMSO) at 10 mM and evaluated at 11 concentrations. 50 The values ​​were derived through nonlinear regression analysis (Table 1).

[1384] Compounds (Examples) with activity designated as “A” have IC 50 <100 nM, the compound designated as "B" (Example) has an IC 50 > 100 nM was shown.

[1385] Compound A<100 nMB>100 nM Compound A<100 nMB>100 nM1A69A2A70B3B71B4B72A5B73A6A74A7B75B8B76A9B77B10A78B11A79A12A80B13A81A14B82A15B83B16A84B17B85A18B86A19B87B20 A88A21A89A22A90B23B91B24A92B25A93A26A94A27A95B28A96A29A97B30A98B31A99A32A100B33B101B34A102B35A103B36A104B37B10 5A38A106A39B107B40B108B41A109A42B110B43A111B44B112A45A113B46A114A47A115A48A116B49B117A50A118A51B119B52B120A53 B121B54B122A55B123A56A124A57A125A58A126A59A127A60A128B61A129B62A130B63A131B64B132B65A133B66B134A67B135A68A136B

[1386] All of the synthesized compounds of Examples 1 to 136 exhibited excellent inhibitory activity against AAK1.

[1387]

[1388] The foregoing description of the present invention is for illustrative purposes only, and those skilled in the art will readily appreciate that the present invention can be readily modified into other specific forms without altering the technical spirit or essential characteristics of the present invention. Therefore, the embodiments described above should be understood as illustrative in all respects and not restrictive. For example, each component described as a single entity may be implemented in a distributed manner, and similarly, components described as distributed may be implemented in a combined manner.

[1389]

[1390] The scope of the present invention is indicated by the claims set forth below, and all changes or modifications derived from the meaning and scope of the claims and their equivalent concepts should be interpreted as being included in the scope of the present invention.

Claims

A heteroaryl derivative compound represented by the following chemical formula 1, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof: <Chemical Formula 1> In the above formula, A is CH or N, B1, B3, B4 and B5 are C, CH, N or NH, B2 is C, CH, N, NH or O, The B ring is a 5-membered aromatic heterocycle containing 1 to 4 heteroatoms selected from N and O, Y is NH, NR 6 or O, R 2 is H or halogen, R 4 is H, C 1-4 Alkyl, halogen or C 1-4 It is haloalkyl, R 5 is C 1-9 C as straight or branched chain alkyl 3-5 With or without cycloalkyl; or R 6 Connected with, R 5 and R 6 Forming a 5- to 7-membered non-aromatic heterocycle containing N linked to and additionally containing N or O, The above R 5 is singular or plural R 5a Is replaced or not replaced, The above R 5a is C 1-4 alkyl, amino or hydroxy, R 6 is R 5 Connected with, R 5 and R 6 Forming a 5- to 7-membered non-aromatic heterocycle containing N linked to and additionally containing N or O, The above B1 is R b1 Is not replaced or substituted with, The above R b1 Silver C 1-4 Alkyl or; R b2 Connected to form a C ring containing 0 to 2 N and fused with a B ring, The above B2 is R b2 Is replaced or not replaced, The above R b2 is R b1 linked to form a C ring fused with a B ring containing 0 to 2 N, The above B4 is R b4 Is replaced or not replaced, The above R b4 is C 1-4 Alkyl or halogen, The fused ring of the above B ring and C ring is a fused ring of two rings containing 1 to 4 N, R f Is replaced or not replaced, The above R f is halogen, C 1-4 Haloalkyl or C 1-4 It is alkoxy. A compound, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof, characterized in that the B ring in claim 1 is pyrrolyl, pyrazolyl, imidazolyl, isoxazolyl, or triazolyl. In the first paragraph, the R 2 A compound characterized in that it is H, fluoro or chloro, a hydrate thereof, a solvate thereof or a pharmaceutically acceptable salt thereof. In the first paragraph, the R 4 A compound characterized in that it is H, methyl, fluoro, chloro, difluoromethyl or trifluoromethyl, a hydrate thereof, a solvate thereof or a pharmaceutically acceptable salt thereof. In the first paragraph, the R 5 A compound characterized in that it is ethyl, 2-methyl-propyl-, 4-methyl-pentyl-, 2,4-dimethylpentyl-, cyclopropyl-methyl- or cyclobutyl-methyl-, a hydrate thereof, a solvate thereof or a pharmaceutically acceptable salt thereof. In the first paragraph, the R 5 and R 6 A compound characterized in that the non-aromatic heterocycle formed by linking is piperazinyl or morpholino, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof. In the first paragraph, the R 5a A compound characterized in that it is methyl, amino or hydroxy, a hydrate thereof, a solvate thereof or a pharmaceutically acceptable salt thereof. In the first paragraph, the R b1 A compound characterized in that it is methyl, a hydrate thereof, a solvate thereof or a pharmaceutically acceptable salt thereof. A compound, characterized in that the fused ring of the B ring and the C ring in the first paragraph is one selected from the group consisting of the following chemical formulas, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof: . In the first paragraph, the R b4 A compound characterized in that it is methyl or fluoro, a hydrate thereof, a solvate thereof or a pharmaceutically acceptable salt thereof. In the first paragraph, the R f A compound characterized in that it is fluoro, chloro, trifluoromethyl or methoxy, a hydrate thereof, a solvate thereof or a pharmaceutically acceptable salt thereof. In claim 1, a compound characterized in that the compound represented by the chemical formula 1 is any one selected from the group consisting of the following compounds, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof: [1] (S)-1-((6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [2] (S)-1-((6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [3] (S)-1-((6-(1H-pyrrolo[3,2-c]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [4] (S)-1-((6-(1H-pyrrolo[2,3-c]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [5] (S)-1-((6-(7-fluoroimidazo[1,2-a]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [6] (S)-1-((6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [7] (S)-1-((6-(1H-pyrrol-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [8] (S)-1-((6-(2H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [9] (S)-1-((6-(3,5-dimethyl-1H-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [10] (S)-1-((6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [11] (S)-1-((6-(6-fluoro-1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [12] (S)-1-((6-(6-chloro-1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [13] (S)-1-((2-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [14] (S)-1-((2-(difluoromethyl)-6-(isoxazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [15] (S)-1-((2-(difluoromethyl)-6-(1H-imidazol-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [16] (S)-1-((2-(difluoromethyl)-6-(3-fluoro-1H-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [17] (S)-1-((2-(difluoromethyl)-6-(1H-imidazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [18] (S)-1-((2-(difluoromethyl)-6-(1H-pyrrol-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [19] (S)-1-((2-(difluoromethyl)-6-(1H-pyrazol-5-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [20] (S)-1-((2-(difluoromethyl)-6-(2H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [21] (S)-1-((2-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [22] (S)-1-(2-(difluoromethyl)-4-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2,4-dimethylpentan-2-amine, [23] (S)-1-((2-(difluoromethyl)-6-(5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [24] (S)-1-((2-(difluoromethyl)-6-(4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [25] ((S)-1-((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [26] (S)-1-((6-(5-chloro-1H-pyrazolo[3,4-b]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [27] (S)-1-((2-(difluoromethyl)-6-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [28] (S)-1-((2-(difluoromethyl)-6-(6-fluoro-1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [29] (S)-1-((2-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [30] (S)-1-((4-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [31] (S)-1-((4-(difluoromethyl)-6-(2H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [32] ((S)-1-((4-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [33] (S)-1-((5-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [34] (S)-1-((6-(1H-pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [35] (S)-1-((6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [36] (S)-1-((5-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine, [37] (S)-1-((3-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine, [38] (S)-1-((4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine, [39] (S)-1-((6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine, [40] (S)-1-((4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [41] (S)-1-((5-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [42] (S)-1-((3-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-4-yl)oxy)-2,4-dimethylpentan-2-amine, [43] (S)-1-((2-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-4-yl)oxy)-2,4-dimethylpentan-2-amine, [44] (S)-1-((2-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [45] 1-((2-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine, [46] 1-((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine, [47] 1-((2-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine, [48] ​​1-((2-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine, [49] 1-((6-(1H-pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine, [50] 1-((6-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine, [51] 2-((6-(5-chloro-1H-pyrazolo[3,4-b]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-ol, [52] 2-((6-(5-chloro-1H-pyrazolo[3,4-b]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-amine, [53] (S)-1-((4-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine, [54] (S)-1-((5-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [55] (S)-1-((5-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine, [56] (S)-1-(4-(1H-pyrrolo[3,2-b]pyridin-1-yl)phenoxy)-2,4-dimethylpentan-2-amine, [57] (S)-1-((2-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine, [58] (S)-1-((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine, [59] (S)-1-((2-(difluoromethyl)-6-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine, [60] (S)-1-((2-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine, [61] 1-((4-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine, [62] 1-((4-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine, [63] 1-((5-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine, [64] 1-((5-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine, [65] 1-(((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine, [66] 1-(((2-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine, [67] 1-(((2-(difluoromethyl)-6-(2H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine, [68] 1-(((2-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine, [69] 1-(((2-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine, [70] 1-(((6-(1H-pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine, [71] 1-((5-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine, [72] 1-(((5-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine, [73] 1-(((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine, [74] 1-(((2-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine, [75] 1-(((2-(difluoromethyl)-6-(2H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine, [76] 1-(((2-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine, [77] 1-(((6-(1H-pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine, [78] 1-(((6-(2H-1,2,3-triazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine, [79] 1-((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-ol, [80] 1-((2-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2-methylpropan-2-ol, [81] (S)-1-(4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2,4-dimethylpentan-2-amine, [82] (S)-1-((6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine, [83] (S)-1-((6-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine, [84] (S)-1-((6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine, [85] (S)-1-((6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine, [86] (S)-1-((6-(4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine, [87] (S)-1-((6-(6-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine, [88] (S)-1-((6-(6-fluoro-1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine, [89] (S)-1-((6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine, [90] (S)-1-((6-(1H-pyrrolo[2,3-c]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine, [91] (S)-1-((6-(1H-pyrrolo[2,3-b]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine, [92] (S)-1-((6-(1H-pyrrolo[3,2-c]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine, [93] (S)-1-(4-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-4-methylpentan-2-amine, [94] (S)-1-(4-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(trifluoromethyl)phenoxy)-4-methylpentan-2-amine, [95] 1-(((6-(2H-1,2,3-triazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine, [96] 1-(((6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine, [97] 1-(((6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine, [98] 1-(((6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine, [99] 1-(((2-fluoro-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine, [100] 1-(((2-fluoro-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine, [101] 1-(((2-fluoro-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine, [102] 1-(((4-fluoro-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine, [103] 1-(((4-fluoro-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine, [104] 1-(((5-fluoro-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine, [105] 1-(((5-fluoro-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine, [106] 1-(((6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine, [107] 1-(2-(difluoromethyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine, [108]N 1 -(2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)-2-methylpropane-1,2-diamine, [109]N 1 -(2-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)-2-methylpropane-1,2-diamine, [110]N 1 -(6-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(trifluoromethyl)pyridin-3-yl)-2-methylpropane-1,2-diamine, [111]N 1 -(2-(difluoromethyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenyl)-2-methylpropane-1,2-diamine, [112]N-((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-amine, [113]N-((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-amine, [114]N-((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-amine, [115]N-((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-amine, [116]N-((1-aminocyclopropyl)methyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-amine, [117]N-((1-aminocyclopropyl)methyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-amine, [118]N-((1-aminocyclopropyl)methyl)-4-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-amine, [119]N-((1-aminocyclopropyl)methyl)-5-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-amine, [120] 1-((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)amino)-2-methylpropan-2-ol, [121] 1-((2-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)amino)-2-methylpropan-2-ol, [122] 1-(2-chloro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine, [123] 1-(2-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine, [124] 1-(2,5-dichloro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine, [125] 2-methyl-1-(2-methyl-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)propan-2-amine, [126] 1-(2,6-difluoro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine, [127] 1-(2,5-difluoro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine, [128] 5-Fluoro-3-(4-(piperazin-1-yl)phenyl)-1H-pyrrolo[2,3-b]pyridine, [129] 5-Fluoro-3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrrolo[2,3-b]pyridine, [130] 4-(4-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)phenyl)morpholine, [131] 5-Fluoro-3-(5-(piperazin-1-yl)pyridin-2-yl)-1H-pyrrolo[2,3-b]pyridine, [132] 5-Fluoro-3-(5-(4-methylpiperazin-1-yl)pyridin-2-yl)-1H-pyrrolo[2,3-b]pyridine, [133] 4-(6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)morpholine, [134] 4-(2-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)morpholine, [135] 4-(2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)-2,2-dimethylmorpholine, and [136] 3-(6-(difluoromethyl)-5-(3,3-dimethylpiperazin-1-yl)pyridin-2-yl)-1H-pyrrolo[2,3-b]pyridine. A pharmaceutical composition for preventing or treating a disease related to AAK1 inhibition, comprising a heteroaryl derivative compound of any one of claims 1 to 12, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient. A pharmaceutical composition according to claim 13, characterized in that the disease associated with AAK1 inhibition is acute pain, chronic pain, inflammatory pain, neuropathic pain, Parkinson's disease, Alzheimer's disease, schizophrenia, bipolar disorder, muscular dystrophy, and viral infection disease. A pharmaceutical composition comprising a heteroaryl derivative compound of any one of claims 1 to 12, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable additive.

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