Novel heterocyclic amine derivatives and pharmaceutical compositions containing the same compounds.

Abstract

Invention details;

Description

Novel heterocyclic amine derivatives and pharmaceutical compositions containing the same

[0001] The present invention relates to a novel heterocyclic amine useful as a BTK (Bruton's Tyrosine Kinase) and ITK (Interleukin-2 Tyrosine Kinase) inhibitor and a pharmaceutical composition comprising the same.

[0002] BTK (Bruton's Tyrosine Kinase) and ITK (Interleukin-2 Tyrosine Kinase) are members of the TEC (tyrosine kinase expressed in hepatocellular carcinoma) family of kinases that act in various immune responses.

[0003]

[0004] BTK functions as a regulator of not only early B cell development but also mature B cell activation, signaling, and survival. These B cells are activated into mature antibody-producing cells by signaling through the B cell receptor (BCR), which recognizes antigens on the surface of antigen-presenting cells. However, abnormal signaling via the BCR can lead to abnormal B cell proliferation and the formation of pathological autoantibodies, which can induce cancer, autoimmune, and / or inflammatory diseases. Therefore, BTK deficiency can block BCR-mediated signaling during abnormal B cell proliferation. Therefore, inhibition of BTK can block B-cell-mediated disease processes, making the use of BTK inhibitors a useful approach for the treatment of B-cell-mediated diseases.

[0005]

[0006] Furthermore, BTK can be expressed by other cells besides B cells that may be involved in disease. For example, BTK is a key component of Fc-gamma signaling in microglia cells. Specifically, BTK has been shown to be useful in controlling diseases such as multiple sclerosis through the regulation of B cells and microglia (J Kramer et al. Nature Reviews Neurology. 2023). Furthermore, monocytes from XLA patients lacking BTK activity have been shown to produce reduced TNF-alpha following stimulation, suggesting that TNF-alpha-mediated inflammation can be suppressed by BTK inhibitors (see Horwood et al. J. Exp. Med. 197:1603, 2003).

[0007]

[0008] In addition, ITK is known to be an important component of TCR signaling in T cells. T cells are activated by TCR signaling, and activated T cells produce inflammatory cytokines and activate B cells and macrophages, which are associated with autoimmune diseases (Sahu N. et al. Curr Top Med Chem. 2009, 9, 690). In addition, it was recently reported that ITK- / - mice regulate the development of Th17 and Treg cells, confirming its potential as a therapeutic target for autoimmune diseases (Gomez-Rodriguez J. et al. J. Exp. Med. 2014, 211, 529). Recently, the expression of cytokines associated with Th1 and Th17 has been confirmed in autoimmune diseases such as multiple sclerosis, and Th17-associated cytokines IL-17 and IL-23 have been identified as playing an essential role in the pathogenesis of the disease (Shi-Rong Wen. et al. J. Neuroimmunol. 2012. 244, 94-96).

[0009]

[0010] Accordingly, substances that inhibit BTK and ITK, respectively, have been developed. Specifically, as BTK inhibitors, 4-aminopyrazolo[3,4-d]pyrimidinylpiperidine derivatives are disclosed in WO2008 / 039218, hetero compounds such as pyridine, pyrimidine, pyrazine, and pyridazine compounds are disclosed in WO2015 / 061247, and pyrimidinylphenylacrylamide derivatives are disclosed in WO2014 / 055934. In addition, as ITK inhibitors, aminobenzimidazole derivatives were disclosed in WO2005 / 066335, pyridone derivatives were disclosed in WO2005 / 056785, aminothiazole derivatives were disclosed in WO2002 / 050071, and benzimidazole derivatives were disclosed in WO2014 / 036016.

[0011]

[0012] Meanwhile, since autoimmune diseases such as multiple sclerosis are caused by complex causes of B cells and T cells (Kathrine E. Attfield. et al. Nature Reviews Immunology. 2022. 734-750), simultaneously suppressing B cells and T cells may be more effective in treating the disease than suppressing each of them alone.

[0013]

[0014] However, since BTK is a kinase expressed downstream of the B-cell receptor and acts on B cells, and ITK is a kinase expressed downstream of the T-cell receptor and acts on T cells, BTK and ITK have different target substances, so it is not possible to predict the ITK inhibitory effect of a BTK inhibitory effect substance, and thus the development of a substance that dually inhibits BTK and ITK has not been easy.

[0015]

[0016] Accordingly, the inventors of the present invention completed the present invention by studying novel compounds and confirming that compounds with chemical structures different from those of BTK and ITK inhibitors reported to date have excellent BTK and ITK dual activity inhibitory effects. The compounds of the present invention primarily exhibit BTK and ITK inhibitory activity on their own, but it is not excluded that they may exhibit pharmacological effects as agonists after being absorbed into the body, either due to a special internal environment or as products of metabolic processes.

[0017]

[0018] The present invention provides novel heterocyclic amine derivatives useful as BTK and / or ITK inhibitors and pharmaceutical compositions comprising the same.

[0019] To solve the above problem, the present invention provides a compound represented by the following chemical formula 1, or a pharmaceutically acceptable salt thereof:

[0020] [Chemical Formula 1]

[0021]

[0022] In the above chemical formula 1,

[0023] Y1 is a single bond, C 1-4 Alkylene, or C 1-4 It is haloalkylene,

[0024] R1 is C 1-10 Alkyl, C 1-10 Alkoxy, C 3-10 Cycloalkyl, C 6-20 Aryl, N-containing 6-membered heteroaryl, tetrahydrofuranyl, or tetrahydropyranyl,

[0025] Here, R1 is unsubstituted or is halogen, cyano, hydroxy, C 1-4 Alkyl and C 1-4 Substituted with one or more substituents selected from the group consisting of haloalkyl,

[0026] A is a 5-membered or 6-membered heterocycle containing 1 to 3 heteroatoms selected from the group consisting of N, O and S substituted or unsubstituted with a benzene ring; or oxo (=O), provided that the 5-membered or 6-membered heterocycle contains at least one N,

[0027] R2 is independently hydrogen, cyano, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Alkoxy, C 1-4 Haloalkoxy, or -CONH(C 1-4 alkyl),

[0028] k is 1 or 2,

[0029] Y2 is a single bond, -O-, or -O-(C 1-4 alkylene),

[0030] L is any one of the linking groups represented by the following chemical formulas 2a to 2k,

[0031]

[0032]

[0033] In the above chemical formulas 2a to 2k,

[0034] n is 0, 1, 2, or 3,

[0035] Z is each independently halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Alkoxy, or C 1-4 It is haloalkoxy,

[0036] a is independently 0, 1, or 2,

[0037] L' is methylene, ethylene, or methylene-O-methylene,

[0038] v and w are each independently 0, 1, or 2,

[0039] However, v+w is an integer from 0 to 3,

[0040] p to s are each independently 0, 1, 2, 3, or 4,

[0041] However, p+q and r+s are integers from 2 to 4, respectively.

[0042] * is the point connected to Y2 of the above chemical formula 1,

[0043] X is CO or SO2,

[0044] R3 is C 1-4 Alkyl, C 2-4 Alkenyl, or C 2-4 It is alkynyl,

[0045] Here, R3 is unsubstituted or substituted with halogen, NH2, NH(C 1-4 alkyl) and N(C 1-4 It is substituted with one or more substituents selected from the group consisting of alkyl)2.

[0046]

[0047] Preferably, Y1 can be a single bond, methylene, or ethylene.

[0048]

[0049] Preferably, R1 is unsubstituted or substituted with halogen, cyano, hydroxy, C 1-4 Alkyl and C 1-4 It may be substituted with one to three substituents selected from the group consisting of haloalkyl.

[0050]

[0051] More preferably, R1 may be unsubstituted or substituted with one to three substituents selected from the group consisting of chloro, fluoro, cyano, hydroxy, methyl, monofluoromethyl, difluoromethyl and trifluoromethyl.

[0052]

[0053] For example, R1 is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, isohexyl, n-heptyl, isoheptyl, n-oxyl, isoxyl, n-nonyl, isononyl, n-decyl, isodecyl, methoxy, ethoxy, propoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenyl, biphenylyl, terphenylyl, naphthyl, pyridinyl, pyrimidinyl, tetrahydrofuranyl, or tetrahydropyranyl,

[0054] Here, R1 is unsubstituted or is halogen, cyano, hydroxy, C 1-4 Alkyl and C 1-4 It may be substituted with one to three substituents selected from the group consisting of haloalkyl.

[0055]

[0056] Also for example, R1 is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, isohexyl, methoxy, ethoxy, propoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, pyridinyl, tetrahydrofuranyl, or tetrahydropyranyl,

[0057] Here, R1 may be unsubstituted or substituted with one to three substituents selected from the group consisting of chloro, fluoro, cyano, hydroxy, methyl, monofluoromethyl, difluoromethyl and trifluoromethyl.

[0058]

[0059] Also preferably, when Y1 is a single bond, R1 is C 1-10 Alkyl, or C 3-10 It is cycloalkyl,

[0060] Here, R1 is unsubstituted or is halogen, cyano, hydroxy, C 1-4 Alkyl and C 1-4It may be substituted with one or more substituents selected from the group consisting of haloalkyl.

[0061]

[0062] For example, when Y1 is a single bond, R1 is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, isohexyl, cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl,

[0063] Here, R1 may be unsubstituted or substituted with one to three substituents selected from the group consisting of chloro, fluoro, cyano, hydroxy, methyl, monofluoromethyl, difluoromethyl and trifluoromethyl.

[0064]

[0065] Also preferably, Y1 is C 1-4 Alkylene or C 1-4 In case of haloalkylene, R1 is C 1-10 Alkoxy, C 3-10 Cycloalkyl, C 6-20 Aryl, N-containing 6-membered heteroaryl, tetrahydrofuranyl, or tetrahydropyranyl,

[0066] Here, R1 is unsubstituted or is halogen, cyano, hydroxy, C 1-4 Alkyl and C 1-4 It may be substituted with one or more substituents selected from the group consisting of haloalkyl.

[0067]

[0068] For example, if Y1 is C 1-4 Alkylene or C 1-4 When haloalkylene, specifically, for example, when Y1 is methylene or ethylene, R1 is methoxy, ethoxy, propoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, pyridinyl, tetrahydrofuranyl, or tetrahydropyranyl,

[0069] Here, R1 may be unsubstituted or substituted with one to three substituents selected from the group consisting of chloro, fluoro, cyano, hydroxy, methyl, monofluoromethyl, difluoromethyl and trifluoromethyl.

[0070]

[0071] Preferably, A can be a benzene, thiazole, thiadiazole, imidazole, pyrazole, pyrazine, pyridine, pyrimidine, or pyridin-2(1H)-one ring.

[0072]

[0073] More preferably, can be represented by any one of the following chemical formulas A1 to A12:

[0074]

[0075]

[0076] In the above chemical formulas A1 to A12,

[0077] R2 is as defined in the above chemical formula 1.

[0078]

[0079] Preferably, R2 can each independently be hydrogen, chloro, fluoro, cyano, methyl, ethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, methoxy, or -CONH(methyl).

[0080]

[0081] Meanwhile, k represents the number of R2, and when k is 2, two R2s can be the same or different.

[0082]

[0083] More preferably,

[0084] A is a benzene, thiazole, thiadiazole, pyrazine, pyridine, or pyridin-2(1H)-one ring, and R2 is each independently halogen, cyano, C 1-4 Alkyl, C 1-4 Haloalkyl, C1-4 Alkoxy, C 1-4 Haloalkoxy, or -CONH(methyl);

[0085] A is an imidazole ring and R2 is hydrogen; or

[0086] A is a pyrazole or pyrimidine ring, and R2 is each independently hydrogen, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Alkoxy, or C 1-4 It may be a haloalkoxy.

[0087]

[0088] Preferably, Y2 can be a single bond, -O-, or -O-(methylene).

[0089]

[0090] At this time, if Y2 is -O-(methylene), (methylene) can be connected to L.

[0091]

[0092] Preferably, when Y2 is a single bond, L may be any one of the linking groups represented by the above chemical formulas 2a to 2g.

[0093]

[0094] For example, when Y2 is a single bond, L can be any one of the linking groups represented by the above chemical formulae 2a, 2b, 2c, 2e, 2f and 2g.

[0095]

[0096] Also preferably, Y2 is -O- or -O-(C 1-4 In the case of alkylene, L may be any one of the linking groups represented by the above chemical formulas 2h to 2k.

[0097]

[0098] For example, when Y2 is -O-, L can be a linking group represented by the above chemical formula 2i or 2k.

[0099]

[0100] Also, for example, Y2 is -O-(C 1-4 In the case of alkylene, L may be a linking group represented by the above chemical formula 2h or 2i.

[0101]

[0102] Meanwhile, a represents the number of Z, and if a is 2, two Zs can be the same or different.

[0103]

[0104] Preferably, L may be any one of the linking groups represented by the above chemical formulae 2a, 2b, 2c, 2e, 2f, 2g, 2h, 2i and 2k.

[0105]

[0106] For example, in the above chemical formula 2a, n may be 2 and a may be 0.

[0107]

[0108] Also, for example, in the above chemical formula 2b, n can be 1 or 2, and a can be 0 or 1.

[0109]

[0110] Also, for example, in the above chemical formula 2c, L' may be methylene-O-methylene and a may be 0.

[0111]

[0112] Also, for example, in the chemical formula 2e, v and w may each be 1, and a may be 0.

[0113]

[0114] Also, for example, in the above chemical formula 2f, v and w may each be 1; or v may be 1, w may be 2, and a may be 0.

[0115]

[0116] Also, for example, in the above chemical formula 2g, a can be 0, 1, or 2.

[0117]

[0118] Also, for example, in the chemical formula 2h, n may be 0, 1, or 2, and a may be 0, 1, or 2.

[0119]

[0120] Also, for example, in the above chemical formula 2i, n may be 0, 1, or 2, and a may be 0, 1, or 2.

[0121]

[0122] Also, for example, in the above chemical formula 2k, p and q may each independently be 1 or 2, r may be 0 or 1, and s may be 2, 3, or 4.

[0123]

[0124] At this time, p+q can be 2 or 3, and r+s can be 2, 3, or 4.

[0125]

[0126] Also preferably, L may be any one of the linking groups selected from the group represented by:

[0127]

[0128] In the above,

[0129] Z and a are as defined in the above chemical formula 1,

[0130] * indicates a point connected to Y2 of the above chemical formula 1.

[0131]

[0132] Preferably, **-Y2-L- may be any one of the linking groups represented by the following chemical formulae 3a to 3r:

[0133]

[0134]

[0135] In the above chemical formulas 3a to 3r,

[0136] m is 0 or 1,

[0137] Z and a are as defined in the above chemical formula 1,

[0138] ** indicates the point connected to the 4th carbon of the pyrrolo[3,2-c]pyridine ring of the above chemical formula 1.

[0139]

[0140] Also, for example, when Y2 is -O-, the compound may be a stereoisomer represented by the following formula 1A or 1B, or a mixture thereof:

[0141] [Chemical Formula 1A]

[0142]

[0143] [Chemical Formula 1B]

[0144]

[0145] In the above chemical formulas 1A and 1B,

[0146] Y1, R1, A, R2, k, L, X and R3 are as defined in the above chemical formula 1.

[0147]

[0148] Also, for example, when Y2 is -O-(methylene), the compound may be a stereoisomer represented by the following formula 1C or 1D, or a mixture thereof:

[0149] [Chemical Formula 1C]

[0150]

[0151] [Chemical Formula 1D]

[0152]

[0153] In the above chemical formulas 1C and 1D,

[0154] Y1, R1, A, R2, k, L, X and R3 are as defined in the above chemical formula 1.

[0155]

[0156] Preferably, Z can be chloro, fluoro, methyl, or methoxy.

[0157]

[0158] Preferably, R3 may be unsubstituted or substituted with one or two substituents selected from the group consisting of chloro, fluoro, NH2, NH(methyl) and N(methyl)2.

[0159]

[0160] More preferably, R3 is -CH3, -CH=CH2, -CH=CHCH3, -C≡CH, or -C≡CCH3,

[0161] Here, R3 may be unsubstituted or substituted with one or two substituents selected from the group consisting of chloro, fluoro, NH2, NH(methyl) and N(methyl)2.

[0162]

[0163] For example, R3 can be -CH3, -CH2Cl, -CH=CH2, -CF=CH2, -CH=CHCH3, -CH=CHCH2N(CH3)2, -C≡CH, or -C≡CCH3.

[0164]

[0165] Meanwhile, the compound represented by the above chemical formula 1 may be represented by any one of the following chemical formulas 1-1 to 1-3:

[0166] [Chemical Formula 1-1]

[0167]

[0168] [Chemical Formula 1-2]

[0169]

[0170] [Chemical Formula 1-3]

[0171]

[0172] In the above chemical formulas 1-1 to 1-3,

[0173] R'2 is halogen, cyano, C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Alkoxy, C 1-4Haloalkoxy, or -CONH(C 1-4 alkyl),

[0174] Y1, R1, A, R2, Y2, L and R3 are as defined in the above chemical formula 1.

[0175]

[0176] For example, R'2 can be chloro, fluoro, cyano, methyl, ethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, methoxy, or -CONH(methyl).

[0177]

[0178] Preferably, in the above chemical formula 1-1,

[0179] A is a thiazole, thiadiazole, imidazole, pyrazole, pyrazine, pyridine, pyrimidine, or pyridin-2(1H)-one ring,

[0180] L may be any one of the linking groups represented by the above chemical formulas 2a, 2b, 2c, 2e, 2f, 2g, 2h, 2i and 2k.

[0181]

[0182] Preferably, in the above chemical formula 1-2,

[0183] A is a benzene ring,

[0184] L may be a linking group represented by the above chemical formula 2i.

[0185]

[0186] Preferably, in the above chemical formula 1-3,

[0187] A is a thiazole ring,

[0188] L may be a linking group represented by the above chemical formula 2i.

[0189]

[0190] Preferably, A is the chemical formula A1,

[0191] R2 is halogen, cyano, C 1-4 Alkyl, C 1-4Haloalkyl, or -CONH(C 1-4 alkyl),

[0192] Y2 is a single bond, -O-, or -O-(C 1-4 alkylene),

[0193] L may be any one of the linking groups represented by the above chemical formulas 2a to 2c and 2e to 2k.

[0194]

[0195] Preferably, A is the chemical formula A2,

[0196] R2 is C 1-4 Alkyl or C 1-4 It is haloalkyl,

[0197] Y2 is a single bond,

[0198] L may be a linking group represented by the above chemical formula 2b.

[0199]

[0200] Preferably, A is the chemical formula A3,

[0201] R2 is hydrogen,

[0202] Y2 is a single bond,

[0203] L may be a linking group represented by the above chemical formula 2b.

[0204]

[0205] Preferably, A is the chemical formula A4,

[0206] R2 is C 1-4 Alkyl or C 1-4 It is haloalkyl,

[0207] Y2 is a single bond,

[0208] L may be a linking group represented by the above chemical formula 2b.

[0209]

[0210] Preferably, A is the chemical formula A5 or A6,

[0211] R2 is hydrogen, halogen, C 1-4Alkyl, C 1-4 Haloalkyl, C 1-4 Alkoxy, or C 1-4 It is haloalkoxy,

[0212] Y2 is -O-,

[0213] L may be a linking group represented by the above chemical formula 2i.

[0214]

[0215] Preferably, A is the chemical formula A7,

[0216] R2 is halogen, C 1-4 Alkyl or C 1-4 It is haloalkyl,

[0217] Y2 is a single bond,

[0218] L may be a linking group represented by the above chemical formula 2b.

[0219]

[0220] Preferably, A is the above chemical formula A8,

[0221] R2 is hydrogen, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Alkoxy, or C 1-4 It is haloalkoxy,

[0222] Y2 is a single bond or -O-,

[0223] L may be a linking group represented by the above chemical formula 2b or 2i.

[0224]

[0225] Preferably, A is the chemical formula A9,

[0226] R2 is hydrogen, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Alkoxy, or C 1-4 It is haloalkoxy,

[0227] Y2 is -O-,

[0228] L may be a linking group represented by the above chemical formula 2i.

[0229]

[0230] Preferably, A is the chemical formula A10,

[0231] R2 is C 1-4 Alkoxy or C 1-4 It is haloalkoxy,

[0232] Y2 is -O-,

[0233] L may be a linking group represented by the above chemical formula 2i.

[0234]

[0235] Preferably, A is the chemical formula A11,

[0236] R2 is C 1-4 Alkyl or C 1-4 It is haloalkyl,

[0237] Y2 is -O-,

[0238] L may be a linking group represented by the above chemical formula 2i.

[0239]

[0240] Preferably, A is the chemical formula A12,

[0241] R2 is independently halogen, C 1-4 Alkyl, or C 1-4 It is haloalkyl,

[0242] Y2 is -O-,

[0243] L may be a linking group represented by the above chemical formula 2i.

[0244]

[0245] Meanwhile, representative examples of compounds represented by the chemical formula 1 are as follows:

[0246] 1) 1-(4-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one,

[0247] 2) 1-(4-(1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one,

[0248] 3) 1-(3-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-2,5-dihydro-1H-pyrrol-1-yl)prop-2-en-1-one,

[0249] 4) 1-(4-(1-(cyclopropylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one,

[0250] 5) 1-(4-(1-cyclopentyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one,

[0251] 6) 1-(4-(1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one,

[0252] 7) 1-(4-(1-(cyclobutylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one,

[0253] 8) 1-(4-(6-((5-methylthiazol-2-yl)amino)-1-((tetrahydrofuran-3-yl)methyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one,

[0254] 9) 1-(4-(1-(cyclohexylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one,

[0255] 10) 1-(4-(1-(cyclopentylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one,

[0256] 11) 1-(4-(1-((4,4-difluorocyclohexyl)methyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one,

[0257] 12) 1-(4-(1-(2,2-difluoroethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one,

[0258] 13) (S)-1-(4-(1-(sec-butyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one,

[0259] 14) (R)-1-(4-(1-(sec-butyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one,

[0260] 15) 1-(4-(1-Benzyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one,

[0261] 16) 1-(4-(6-((5-methylthiazol-2-yl)amino)-1-phenethyl-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one,

[0262] 17) 1-(4-(6-((5-methylthiazol-2-yl)amino)-1-((1-(trifluoromethyl)cyclopropyl)methyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one,

[0263] 18) 1-(4-(1-(3,3-dimethylbutyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one,

[0264] 19) 1-(4-(6-((5-methylthiazol-2-yl)amino)-1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one,

[0265] 20) 1-(4-(1-(2,2-difluorocyclopropyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one,

[0266] 21) 1-(4-(1-(difluoromethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one,

[0267] 22) 2-(4-(1-Acryloyl-1,2,3,6-tetrahydropyridin-4-yl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-1-yl)-2-methylpropanenitrile,

[0268] 23) 2-(4-(1-Acryloyl-1,2,5,6-tetrahydropyridin-3-yl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-1-yl)-2-methylpropanenitrile,

[0269] 24) (R)-1-(4-(6-((5-methylthiazol-2-yl)amino)-1-(1,1,1-trifluoropropan-2-yl)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one,

[0270] 25) 1-(4-(1-(2,2-difluoroethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3-methyl-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one,

[0271] 26) 1-(4-(1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-2,3,6,7-tetrahydro-1H-azepin-1-yl)prop-2-en-1-one,

[0272] 27) 1-(7-(1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3-oxa-9-azabicyclo[3.3.1]non-6-en-9-yl)prop-2-en-1-one,

[0273] 28) 1-(3-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-8-azabicyclo[3.2.1]oct-2-en-8-yl)prop-2-en-1-one,

[0274] 29) 1-(3-(1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-8-azabicyclo[3.2.1]oct-2-en-8-yl)prop-2-en-1-one,

[0275] 30) 1-(3-(6-((5-methylthiazol-2-yl)amino)-1-((1-(trifluoromethyl)cyclopropyl)methyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)-8-azabicyclo[3.2.1]oct-2-en-8-yl)prop-2-en-1-one,

[0276] 31) 1-(3-(1-(2,2-difluorocyclopropyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-8-azabicyclo[3.2.1]oct-2-en-8-yl)prop-2-en-1-one,

[0277] 32) 1-(3-(1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-8-azabicyclo[3.2.1]oct-2-en-8-yl)prop-2-en-1-one,

[0278] 33) 1-(3-(1-cyclopentyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-8-azabicyclo[3.2.1]oct-2-en-8-yl)prop-2-en-1-one,

[0279] 34) 1-(3-(1-(2,2-difluoroethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-8-azabicyclo[3.2.1]oct-2-en-8-yl)prop-2-en-1-one,

[0280] 35) 1-(3-(6-((5-methylthiazol-2-yl)amino)-1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)-8-azabicyclo[3.2.1]oct-2-en-8-yl)prop-2-en-1-one,

[0281] 36) 1-(3-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-9-azabicyclo[3.3.1]non-2-en-9-yl)prop-2-en-1-one,

[0282] 37) 1-(3-(1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-9-azabicyclo[3.3.1]non-2-en-9-yl)prop-2-en-1-one,

[0283] 38) 1-(3-(1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-9-azabicyclo[3.3.1]non-2-en-9-yl)prop-2-en-1-one,

[0284] 39) 1-(3-(1-(cyclopropylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-8-azabicyclo[3.2.1]oct-2-en-8-yl)prop-2-en-1-one,

[0285] 40) 1-(4-(6-((1H-imidazol-2-yl)amino)-1-methyl-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one,

[0286] 41) 1-(4-(1-isopropyl-6-((5-methyl-1,3,4-thiadiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one,

[0287] 42) 1-(4-(1-isopropyl-6-((4-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one,

[0288] 43) 1-(4-(1-isopropyl-6-(pyrimidin-4-ylamino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one,

[0289] 44) 1-(4-(1-isopropyl-6-((6-methylpyrimidin-4-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one,

[0290] 45) 1-(4-(1-isopropyl-6-((6-(trifluoromethyl)pyrimidin-4-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one,

[0291] 46) 1-(4-(1-isopropyl-6-((6-methoxypyrimidin-4-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one,

[0292] 47) 1-(4-(6-((4-fluoropyridin-2-yl)amino)-1-isopropyl-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one,

[0293] 48) 1-(4-(1-isopropyl-6-((4-(trifluoromethyl)pyridin-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one,

[0294] 49) 1-(4-(1-isopropyl-6-((4-methylpyridin-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one,

[0295] 50)N-(3-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide,

[0296] 51)N-(2-fluoro-3-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide,

[0297] 52)N-(2-methoxy-3-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide,

[0298] 53)N-(3-methyl-5-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide,

[0299] 54)N-(2-fluoro-5-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide,

[0300] 55)N-(2-methyl-5-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide,

[0301] 56)N-(2,6-dimethyl-3-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide,

[0302] 57)N-(2,6-difluoro-3-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide,

[0303] 58)N-(3-(1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-2-methylphenyl)acrylamide,

[0304] 59)N-(4-fluoro-3-(1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide,

[0305] 60)N-(2,4-difluoro-5-(1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide,

[0306] 61)N-(3-(1-(cyclopropylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-4-fluorophenyl)acrylamide,

[0307] 62)N-(3-(1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-2-methylphenyl)acrylamide,

[0308] 63)N-(4-fluoro-3-(1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide,

[0309] 64)N-(5-(1-(cyclopropylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-2-fluorophenyl)acrylamide,

[0310] 65)N-(5-(1-(cyclopropylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-2-methylphenyl)acrylamide,

[0311] 66)N-(5-(1-(cyclopropylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-2,4-difluorophenyl)acrylamide,

[0312] 67)N-(2,4-difluoro-5-(1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide,

[0313] 68) (S)-N-(3-(1-(sec-butyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-4-fluorophenyl)acrylamide,

[0314] 69)N-(5-(1-(3,3-dimethylbutyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-2,4-difluorophenyl)acrylamide,

[0315] 70)N-(3-(1-cyclopentyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-4-fluorophenyl)acrylamide,

[0316] 71)N-(4-fluoro-3-(6-((5-methylthiazol-2-yl)amino)-1-((tetrahydrofuran-3-yl)methyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide,

[0317] 72)N-(2-fluoro-5-(6-((5-methylthiazol-2-yl)amino)-1-((tetrahydrofuran-3-yl)methyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide,

[0318] 73)N-(2-fluoro-3-(6-((5-methylthiazol-2-yl)amino)-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide,

[0319] 74)N-(5-(1-(2,2-difluoroethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-2-methylphenyl)acrylamide,

[0320] 75)N-(3-(1-(2,2-difluoroethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-4-fluorophenyl)acrylamide,

[0321] 76)N-(5-(1-(2,2-difluoroethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-2-fluorophenyl)acrylamide,

[0322] 77)N-(2,4-difluoro-5-(6-((5-methylthiazol-2-yl)amino)-1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide,

[0323] 78) N-(4-fluoro-3-(6-((5-methylthiazol-2-yl)amino)-1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide,

[0324] 79) (S)-1-(3-((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0325] 80) 1-(3-((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)azetidin-1-yl)prop-2-en-1-one,

[0326] 81) (S)-1-(3-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0327] 82) (R)-1-(3-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0328] 83) 1-((3S,4R)-3-fluoro-4-((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0329] 84) (S)-1-(3-((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)piperidin-1-yl)prop-2-en-1-one,

[0330] 85) (S)-1-(2-(((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl )pyrrolidin-1-yl)prop-2-en-1-one,

[0331] 86) (S)-1-(2-(((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl )azetidin-1-yl)prop-2-en-1-one,

[0332] 87) 1-((2R,4S)-4-((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-2-methylpyrrolidin-1-yl)prop-2-en-1-one,

[0333] 88) 1-((2S,4S)-4-((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-2-methylpyrrolidin-1-yl)prop-2-en-1-one,

[0334] 89) (R)-1-(2-(((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl)pyrrolidin-1-yl)prop-2-en-1-one,

[0335] 90) (R)-1-(2-(((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl)azetidin-1-yl)prop-2-en-1-one,

[0336] 91) 1-((3R,4R)-3-fluoro-4-((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0337] 92)Rac-1-((3S,4R)-3-((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-4-methylpyrrolidin-1-yl)prop-2-en-1-one,

[0338] 93) (R)-1-(4,4-difluoro-2-(((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl)pyrrolidin-1-yl)prop-2-en-1-one,

[0339] 94) 1-((2R,4S)-2-(((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl)-4-methoxypyrrolidin-1-yl)prop-2-en-1-one,

[0340] 95) (S)-1-(3-((1-isopropyl-6-((6-(trifluoromethyl)pyrimidin-4-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0341] 96) 1-((2R,4S)-4-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-2-methylpyrrolidin-1-yl)prop-2-en-1-one,

[0342] 97) (S)-1-(3-((1-(cyclopropylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0343] 98) 1-((2R,4S)-4-((1-(cyclopropylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-2-methylpyrrolidin-1-yl)prop-2-en-1-one,

[0344] 99) (S)-1-(3-((1-cyclopentyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0345] 100) 1-((2R,4S)-4-((1-cyclopentyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-2-methylpyrrolidin-1-yl)prop-2-en-1-one,

[0346] 101) (S)-1-(3-((1-isopropyl-6-((6-methylpyrimidin-4-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0347] 102) (S)-1-(3-((6-((5-methylthiazol-2-yl)amino)-1-((1-(trifluoromethyl)cyclopropyl)methyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0348] 103) (S)-1-(3-((1-isopropyl-6-((6-methoxypyrimidin-4-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0349] 104) (S)-1-(3-((1-isobutyl-6-((6-methylpyrimidin-4-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0350] 105) 1-((3S,4R)-3-fluoro-4-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0351] 106) 1-((3R,4R)-3-fluoro-4-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0352] 107) 1-((3R,4S)-3-((1-(cyclopropylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-4-fluoropyrrolidin-1-yl)prop-2-en-1-one,

[0353] 108) 1-((3R,4R)-3-((1-(cyclopropylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-4-fluoropyrrolidin-1-yl)prop-2-en-1-one,

[0354] 109) 1-((3R,4S)-3-((1-cyclopentyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-4-fluoropyrrolidin-1-yl)prop-2-en-1-one,

[0355] 110) 1-((3R,4R)-3-((1-cyclopentyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-4-fluoropyrrolidin-1-yl)prop-2-en-1-one,

[0356] 111) 1-((S)-3-((1-((S)-sec-butyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0357] 112) 1-((3R,4S)-3-((1-((S)-sec-butyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-4-fluoropyrrolidin-1-yl)prop-2-en-1-one,

[0358] 113) 1-((3R,4R)-3-((1-((S)-sec-butyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-4-fluoropyrrolidin-1-yl)prop-2-en-1-one,

[0359] 114) (S)-1-(3-((1-isopentyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0360] 115) 1-((3R,4R)-3-fluoro-4-((1-isopentyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0361] 116) 1-(3-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-4-methylpyrrolidin-1-yl)prop-2-en-1-one,

[0362] 117) (S)-1-(3-((6-((5-methylthiazol-2-yl)amino)-1-(pyridin-2-ylmethyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0363] 118) 1-(3-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)azetidin-1-yl)prop-2-en-1-one,

[0364] 119) 1-(3-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-3-methylazetidin-1-yl)prop-2-en-1-one,

[0365] 120) 1-((3R,4R)-3-fluoro-4-((6-((5-methylthiazol-2-yl)amino)-1-((1-(trifluoromethyl)cyclopropyl)methyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0366] 121) (S)-1-(3-((1-benzyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0367] 122) (S)-1-(3-((6-((5-ethylthiazol-2-yl)amino)-1-isobutyl-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0368] 123) 1-((3S)-3-((1-(2-methylbutyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0369] 124) (S)-1-(3-((1-butyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0370] 125) (S)-1-(3-((1-ethyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0371] 126) (S)-1-(3-((6-((5-methylthiazol-2-yl)amino)-1-propyl-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0372] 127) (S)-1-(3-((1-(2-methoxyethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0373] 128) (S)-1-(3-((1-(cyclopentylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0374] 129) (S)-1-(3-((1-(cyclohexylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0375] 130) (S)-1-(3-((1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0376] 131) 1-((3S,4R)-3-fluoro-4-((1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0377] 132) 1-((3R,4S)-3-((1-(cyclopentylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-4-fluoropyrrolidin-1-yl)prop-2-en-1-one,

[0378] 133) (S)-1-(3-((6-((5-methylthiazol-2-yl)amino)-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0379] 134) 1-((3S,4S)-3-fluoro-4-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0380] 135) 1-((3R,4S)-3-fluoro-4-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0381] 136) 1-(6-((1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-1-azaspiro[3.3]heptan-1-yl)prop-2-en-1-one,

[0382] 137) 1-(6-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-1-azaspiro[3.3]heptan-1-yl)prop-2-en-1-one,

[0383] 138) (S)-1-(3-((6-((5-fluoro-2-methylphenyl)amino)-1-methyl-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0384] 139) 1-((3S,4R)-3-fluoro-4-((6-((5-fluoro-2-methylphenyl)amino)-1-methyl-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0385] 140) (S)-1-(3-((1-(2-hydroxy-2-methylpropyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0386] 141) 1-((3S,4R)-3-fluoro-4-((1-(2-hydroxy-2-methylpropyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0387] 142) 1-(3-((1-cyclopentyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)azetidin-1-yl)prop-2-en-1-one,

[0388] 143) (R)-1-(3-((1-cyclopentyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0389] 144) (R)-1-(3-((1-(cyclopropylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0390] 145) 1-(3-((1-(cyclopropylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)azetidin-1-yl)prop-2-en-1-one,

[0391] 146) 1-(3-((1-(2-methoxyethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)azetidin-1-yl)prop-2-en-1-one,

[0392] 147) 1-((3S,4R)-3-fluoro-4-((1-(2-methoxyethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c] pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0393] 148) (S)-1-(3-((1-(2-methoxyethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)piperidin-1-yl)prop-2-en-1-one,

[0394] 149) (S)-1-(3-((1-(cyclopropylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy) piperidin-1-yl)prop-2-en-1-one,

[0395] 150) (S)-1-(3-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)piperidin-1-yl)prop-2-en-1-one,

[0396] 151) (S)-1-(3-((1-cyclopentyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)piperidin-1-yl)prop-2-en-1-one,

[0397] 152) 1-((3R,4S)-3-((1-ethyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-4-fluoropyrrolidin-1-yl)prop-2-en-1-one,

[0398] 153) (S)-1-(3-((1-ethyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)piperidin-1-yl)prop-2-en-1-one,

[0399] 154) 1-((3R,4R)-3-((1-ethyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-4-fluoropyrrolidin-1-yl)prop-2-en-1-one,

[0400] 155) 1-(3-((1-ethyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-3-methylazetidin-1-yl)prop-2-en-1-one,

[0401] 156) (R)-1-(3-((1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0402] 157) 1-((3R,4R)-3-fluoro-4-((1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0403] 158) (S)-1-(3-((1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)piperidin-1-yl)prop-2-en-1-one,

[0404] 159) 1-((3S,4R)-3-fluoro-4-((6-((5-methylthiazol-2-yl)amino)-1-propyl-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0405] 160) (S)-1-(3-((6-((5-methylthiazol-2-yl)amino)-1-propyl-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)piperidin-1-yl)prop-2-en-1-one,

[0406] 161) 1-((3R,4R)-3-fluoro-4-((6-((5-methylthiazol-2-yl)amino)-1-propyl-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0407] 162) (R)-1-(3-((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0408] 163) 1-(3-((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-3-methylazetidin-1-yl)prop-2-en-1-one,

[0409] 164) 1-((2S,4S)-4-((1-cyclopentyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-2-methylpyrrolidin-1-yl)prop-2-en-1-one,

[0410] 165) 1-(3-((1-cyclopentyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-3-methylazetidin-1-yl)prop-2-en-1-one,

[0411] 166) 1-(3-methyl-3-((1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)azetidin-1-yl)prop-2-en-1-one,

[0412] 167) 1-(3-((1-(cyclopropylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-3-methylazetidin-1-yl)prop-2-en-1-one,

[0413] 168) 1-(3-((1-(2-methoxyethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-3-methylazetidin-1-yl)prop-2-en-1-one,

[0414] 169) (S)-1-(3-((1-(cyclopentylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy) piperidin-1-yl)prop-2-en-1-one,

[0415] 170) 1-((3R,4R)-3-((1-(cyclopentylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-4-fluoropyrrolidin-1-yl)prop-2-en-1-one,

[0416] 171) 1-((3S,4R)-3-fluoro-4-((1-(2-methylbutyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0417] 172) 1-((3S)-3-((1-(2-methylbutyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)piperidin-1-yl)prop-2-en-1-one,

[0418] 173) 1-((3R,4R)-3-fluoro-4-((1-(2-methylbutyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0419] 174) 1-((3R,4R)-3-fluoro-4-((1-((R)-2-methylbutyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0420] 175) 1-((3R,4R)-3-fluoro-4-((1-((S)-2-methylbutyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0421] 176) 1-(3-methyl-3-((6-((5-methylthiazol-2-yl)amino)-1-propyl-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)azetidin-1-yl)prop-2-en-1-one,

[0422] 177) 1-(3-((1-isopentyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-3-methylazetidin-1-yl)prop-2-en-1-one,

[0423] 178) 1-(3-((1-(cyclopentylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-3-methylazetidin-1-yl)prop-2-en-1-one,

[0424] 179) 1-((2S,4S)-4-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-2-methylpyrrolidin-1-yl)prop-2-en-1-one,

[0425] 180) 1-((2S,4S)-4-((1-(cyclopropylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-2-methylpyrrolidin-1-yl)prop-2-en-1-one,

[0426] 181) 2-((4-(((3R,4S)-1-Acryloyl-4-fluoropyrrolidin-3-yl)oxy)-1-isobutyl-1H-pyrrolo[3,2-c]pyridin-6-yl)amino)thiazole-5-carbonitrile,

[0427] 182) 2-((4-(((3R,4S)-1-acryloyl-4-fluoropyrrolidin-3-yl)oxy)-1-isobutyl-1H-pyrrolo[3,2-c]pyridin-6-yl)amino)-N-methylthiazole-5-carboxamide,

[0428] 183) (S)-1-(3-((1-isopropyl-6-((4-methoxypyrimidin-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0429] 184) (S)-1-(3-((1-isopropyl-6-((3-methoxypyrazin-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0430] 185) 1-((2S,4S)-2-methyl-4-((1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0431] 186) 1-((2S,4S)-4-((1-ethyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-2-methylpyrrolidin-1-yl)prop-2-en-1-one,

[0432] 187) 1-((2S,4S)-2-methyl-4-((6-((5-methylthiazol-2-yl)amino)-1-propyl-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0433] 188) (S)-1-(3-((1-(2-fluoroethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0434] 189) 1-((3S,4R)-3-fluoro-4-((1-(2-fluoroethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0435] 190) (S)-1-(3-((1-(3-fluoropropyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0436] 191) 1-((3S,4R)-3-fluoro-4-((1-(3-fluoropropyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0437] 192) (S)-1-(3-((6-((1H-pyrazol-3-yl)amino)-1-isopropyl-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0438] 193) (S)-1-(3-((1-isopropyl-6-((1-methyl-1H-pyrazol-3-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0439] 194) (S)-1-(3-((1-isopropyl-6-((5-methyl-1H-pyrazol-3-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0440] 195) 1-((3R,4S)-3-((6-((1H-pyrazol-3-yl)amino)-1-isobutyl-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-4-fluoropyrrolidin-1-yl)prop-2-en-1-one,

[0441] 196) 1-((3S,4R)-3-fluoro-4-((1-isobutyl-6-((5-methyl-1H-pyrazol-3-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0442] 197) 1-((3S,4R)-3-fluoro-4-((1-isobutyl-6-((1-methyl-1H-pyrazol-3-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0443] 198) (S)-3-((4-((1-Acryloylpyrrolidin-3-yl)oxy)-1-isopropyl-1H-pyrrolo[3,2-c]pyridin-6-yl)amino)-1-methylpyridin- 2(1H)-1-one,

[0444] 199) 3-((4-(((3R,4S)-1-acryloyl-4-fluoropyrrolidin-3-yl)oxy)-1-isobutyl-1H-pyrrolo[3,2-c]pyridin-6-yl)amino)-1-methylpyridin-2(1H)-one,

[0445] 200) 1-(2-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-5-azaspiro[3.4]octan-5-yl)prop-2-en-1-one,

[0446] 201) 1-(7-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-1-azaspiro[4.4]nonan-1-yl)prop-2-en-1-one,

[0447] 202) 1-(2-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-6-azaspiro[3.4]octan-6-yl)prop-2-en-1-one,

[0448] 203) 1-(2-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-5-azaspiro[3.5]nonan-5-yl)prop-2-en-1-one,

[0449] 204) 1-(7-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-2-azaspiro[4.4]nonan-2-yl)prop-2-en-1-one,

[0450] 205) (S)-1-(3-((6-((5-methylthiazol-2-yl)amino)-1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0451] 206) (S)-1-(3-((1-(2,2-difluoroethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0452] 207) (R)-1-(2-(((6-((5-methylthiazol-2-yl)amino)-1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl)pyrrolidin-1-yl)prop-2-en-1-one,

[0453] 208) (R)-1-(2-(((6-((5-methylthiazol-2-yl)amino)-1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl)azetidin-1-yl)prop-2-en-1-one,

[0454] 209) (R)-1-(2-(((1-(2,2-difluoroethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl)azetidin-1-yl)prop-2-en-1-one,

[0455] 210) (R)-1-(2-(((1-(2,2-difluoroethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl)pyrrolidin-1-yl)prop-2-en-1-one,

[0456] 211) 1-((3S,4R)-3-fluoro-4-((6-((5-methylthiazol-2-yl)amino)-1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0457] 212) 1-((2R,4S)-2-methyl-4-((6-((5-methylthiazol-2-yl)amino)-1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0458] 213) 1-((S)-3-((6-((5-methylthiazol-2-yl)amino)-1-((R)-1,1,1-trifluoropropan-2-yl)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0459] 214) (R)-1-(3-(((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl )piperidin-1-yl)prop-2-en-1-one,

[0460] 215) (S)-1-(3-(((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl )piperidin-1-yl)prop-2-en-1-one,

[0461] 216) (S)-1-(3-(((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl)pyrrolidin-1-yl)prop-2-en-1-one,

[0462] 217) 1-(2-(((1-cyclopentyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl)pyrrolidin-1-yl)prop-2-en-1-one,

[0463] 218) 1-(2-(((1-cyclopentyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl)azetidin-1-yl)prop-2-en-1-one,

[0464] 219) (S)-1-(2-(((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl)pyrrolidin-1-yl)prop-2-en-1-one,

[0465] 220) (S)-1-(2-(((1-(cyclopentylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl)pyrrolidin-1-yl)prop-2-en-1-one,

[0466] 221) 1-((2S)-2-(((1-(2-methylbutyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl)pyrrolidin-1-yl)prop-2-en-1-one,

[0467] 222) (S)-1-(2-(((1-cyclopentyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl)pyrrolidin-1-yl)prop-2-en-1-one,

[0468] 223) (R)-1-(2-(((1-cyclopentyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl)azetidin-1-yl)prop-2-en-1-one,

[0469] 224) (S)-2-Fluoro-1-(3-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,

[0470] 225) (S)-1-(3-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-tin-1-one,

[0471] 226) (S,E)-1-(3-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)but-2-en-1-one,

[0472] 227) (S,E)-4-(dimethylamino)-1-(3-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)but-2-en-1-one,

[0473] 228) N-(4-(((3R,4S)-4-fluoro-1-(vinylsulfonyl)pyrrolidin-3-yl)oxy)-1-isobutyl-1H-pyrrolo[3,2-c]pyridin-6-yl)-5-methylthiazol-2-amine,

[0474] 229) 2-chloro-1-((3S,4R)-3-fluoro-4-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)ethan-1-one,

[0475] 230) 1-((3S,4R)-3-fluoro-4-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)but-2-yn-1-one, and

[0476] 231) 1-((3S,4R)-3-fluoro-4-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-yn-1-one.

[0477]

[0478] Meanwhile, the compound represented by the above chemical formula 1 can be understood as a concept encompassing all stereoisomers, mixtures of stereoisomers, and isotopic derivatives of the compound.

[0479]

[0480] Specifically, the "stereoisomers" of the compound may be understood to include all possible structures of diastereomers and enantiomers when the compound contains one or more chiral centers.

[0481]

[0482] Additionally, "isotopic derivatives" of the compound mean that one or more atoms in the compound are replaced with its naturally occurring or non-naturally occurring isotope. For example, isotopic derivatives of the compound include compounds in which at least one hydrogen in the compound is replaced with deuterium.

[0483]

[0484] Furthermore, the compounds of the present invention may exist in the form of salts, particularly pharmaceutically acceptable salts. As salts, any salt commonly used in the art, such as acid addition salts formed with pharmaceutically acceptable free acids, may be used without limitation. The term "pharmaceutically acceptable salt" as used herein refers to any organic or inorganic addition salt of the compound represented by Chemical Formula 1, which has a concentration that is relatively non-toxic and harmless to the patient and has an effective effect, and wherein the side effects caused by the salt do not diminish the beneficial effects of the compound represented by Chemical Formula 1.

[0485]

[0486] As the above-mentioned acid, organic acids and inorganic acids can be used. As the inorganic acid, hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, tartaric acid, etc. can be used. As the organic acid, methanesulfonic acid, p-toluenesulfonic acid, acetic acid, trifluoroacetic acid, maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, mandelic acid, propionic acid, citric acid, lactic acid, glycolic acid, gluconic acid, galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid, ascorbic acid, carbonic acid, vanillic acid, hydroiodic acid, etc. can be used, but are not limited thereto. Preferably, the salt may be hydrochloride.

[0487]

[0488] Additionally, a pharmaceutically acceptable metal salt can be obtained by a conventional method using a base. For example, the compound represented by the above chemical formula 1 is dissolved in an excess alkali metal hydroxide or alkaline earth metal hydroxide solution, the undissolved compound salt is filtered, and the filtrate is evaporated and dried to obtain a pharmaceutically acceptable metal salt. In this case, it is particularly preferable to prepare a sodium salt, a potassium salt, or a calcium salt as the metal salt.

[0489]

[0490] Other pharmaceutically unacceptable salts or solvates of the compound represented by chemical formula 1 can be used as intermediates in the production of the compound represented by chemical formula 1, a pharmaceutically acceptable salt, or solvate thereof.

[0491]

[0492] In addition, the compound represented by the above chemical formula 1 according to the present invention includes, without limitation, not only its pharmaceutically acceptable salt but also solvates such as possible hydrates that can be prepared therefrom or prodrugs thereof.

[0493]

[0494] The solvate of the compound represented by the above chemical formula 1 can be prepared from the compound represented by the chemical formula 1 using a method known in the art.

[0495]

[0496] Additionally, unless otherwise indicated, a "prodrug" of the above compound may be understood to refer to any derivative which can be hydrolyzed, oxidized or otherwise reacted under biological conditions (in vitro or in vivo) to provide the compound of the present invention, a stereoisomer thereof, a mixture of stereoisomers thereof, an isotopic derivative thereof, or a pharmaceutically acceptable salt thereof.

[0497]

[0498] Additionally, the present invention may include not only stoichiometric hydrates of the compound represented by the above chemical formula 1, but also compounds containing various amounts of water. The solvates of the compound represented by the above chemical formula 1 according to the present invention include both stoichiometric solvates and non-stoichiometric solvates.

[0499]

[0500] In addition, the compound represented by the above chemical formula 1 can be prepared through the following reaction scheme 1, for example, when L is any one of the linking groups represented by the above chemical formulas 2a to 2f.

[0501] [Reaction Formula 1]

[0502]

[0503] In the above reaction formula 1, P1 represents a protecting group, and the remaining substituents are as defined in the above chemical formula 1.

[0504] For example, P1 can be any one protecting group selected from the group consisting of tert-butyloxycarbonyl (Boc), carbobenzyloxy (Cbz), para-methoxybenzylcarbonyl (Moz), 9-fluorenylmethyloxycarbonyl (Fmoc), acetyl (Ac), benzoyl (Bz), benzyl (Bn), and para-methoxybenzyl (PMB).

[0505]

[0506] The above step 1-1 is a step of producing a compound represented by the above chemical formula 1-3 by reacting a compound represented by the above chemical formula 1-1 with a compound represented by the above chemical formula 1-2. The above reaction is preferably performed in the presence of a palladium catalyst and a base as a Suzuki-coupling reaction.

[0507]

[0508] The above step 1-2 is a step of producing a compound represented by the above chemical formula 1-5 by reacting a compound represented by the above chemical formula 1-3 with a compound represented by the above chemical formula 1-4. The above reaction is an amine substitution reaction, and is preferably performed in the presence of a palladium catalyst and a base.

[0509]

[0510] The above step 1-3 is a step of removing a protecting group from a compound represented by the above chemical formula 1-5, and then reacting it with a compound represented by the above chemical formula 1-6 or 1-7 to produce a compound represented by the above chemical formula 1. The removal of the protecting group is preferably performed under acid conditions capable of removing the protecting group, such as trifluoroacetic acid (TFA), and the reaction with the compound represented by the above chemical formula 1-6 or 1-7 is an amidation reaction, and is preferably performed in the presence of a base.

[0511]

[0512] In addition, the compound represented by the above chemical formula 1 can be prepared through the following reaction formula 2, for example, when L is a linking group represented by the above chemical formula 2g.

[0513] [Reaction Formula 2]

[0514]

[0515] In the above reaction formula 2, P1 means a protecting group and is as defined in the above reaction formula 1, and the remaining substituents are as defined in the above chemical formula 1.

[0516]

[0517] The above step 2-1 is a step of producing a compound represented by the above chemical formula 1-3 by reacting a compound represented by the above chemical formula 1-1 with a compound represented by the above chemical formula 1-8, and can be performed in the same manner as step 1-1 of the above reaction scheme 1, except that the reactor for the Suzuki-coupling reaction is different.

[0518]

[0519] Additionally, steps 2-2 and 2-3 can be performed in the same manner as steps 1-2 and 1-3 of the above reaction scheme 1, respectively.

[0520]

[0521] In addition, the compound represented by the above chemical formula 1 can be prepared through the following reaction scheme 3, for example, when L is any one of the linking groups represented by the above chemical formulas 2h to 2k.

[0522] [Reaction Formula 3]

[0523]

[0524] In the above reaction formula 3, P1 represents a protecting group and is as defined in the above reaction formula 1, and the remaining substituents are as defined in the above chemical formula 1.

[0525]

[0526] The above step 3-1 is a step of producing a compound represented by the above chemical formula 1-3 by reacting a compound represented by the above chemical formula 1-1 with a compound represented by the above chemical formula 1-9. The above reaction is a nucleophilic substitution reaction and is preferably performed in the presence of a base.

[0527]

[0528] Additionally, steps 3-2 and 3-3 can be performed in the same manner as steps 1-2 and 1-3 of the above reaction scheme 1, respectively.

[0529]

[0530] The manufacturing method of each step described above can be further specified in the examples described below.

[0531]

[0532] In addition, the present invention provides a pharmaceutical composition comprising a compound represented by the above chemical formula 1, or a pharmaceutically acceptable salt thereof, as an active ingredient.

[0533]

[0534] More specifically, the present invention can be understood as providing a pharmaceutical composition comprising a compound represented by the above chemical formula 1, a stereoisomer thereof, a mixture of stereoisomers thereof, an isotopic derivative thereof, a pharmaceutically acceptable salt thereof, or a prodrug thereof as an active ingredient.

[0535]

[0536] In addition, the present invention provides a pharmaceutical composition for preventing or treating inflammatory diseases, autoimmune diseases, or cancer, comprising a compound represented by the above chemical formula 1, or a pharmaceutically acceptable salt thereof, as an active ingredient.

[0537]

[0538] More specifically, the present invention can be understood as providing a pharmaceutical composition for preventing or treating inflammatory diseases, autoimmune diseases, or cancers, which has a beneficial ITK and BTK inhibitory action, and which comprises as an active ingredient a compound represented by the above chemical formula 1, a stereoisomer thereof, a mixture of stereoisomers thereof, an isotopic derivative thereof, a pharmaceutically acceptable salt thereof, or a prodrug thereof.

[0539]

[0540] At this time, the autoimmune disease is rheumatoid arthritis, systemic lupus erythematosus, childhood diabetes, psoriasis, aphthous stomatitis, chronic thyroiditis, some acquired aplastic anemias, primary cirrhosis, ulcerative colitis, Behcet's disease, Crohn's disease, silicosis, asbestosis, Sjogren's syndrome, Guillain-Barré syndrome, dermatomyositis, polymyositis, multiple sclerosis, anti-MOG antibody disease, autoimmune hemolytic anemia, autoimmune encephalomyelitis, myasthenia gravis, Grave's hyperthyroidism, polyarteritis nodosa, ankylosing spondylitis, fibromyalgia, temporal arteritis, Wilson's disease, asthma, neuromyelitis optica, Fanconi syndrome, or degenerative neurological diseases such as Alzheimer's, Parkinson's, and Lou Gehrig's.

[0541] The cancer may be a hematological cancer, extranodal marginal zone B-cell lymphoma, glioblastoma, lymphoplasmacytic lymphoma, acute myeloid leukemia, macroglobulinemia, B-cell lymphoma, chronic lymphocytic leukemia, follicular lymphoma, non-Hodgkin's lymphoma, diffuse large B-cell lymphoma, hairy cell leukemia, mantle cell lymphoma, glioblastoma, bladder cancer, pancreatic cancer, ovarian cancer, colon cancer, kidney cancer, stomach cancer, transitional cell carcinoma, carcinoid tumor, breast cancer, non-small cell lung cancer, or multiple myeloma.

[0542]

[0543] The term "prevention" of the present invention means any act of inhibiting or delaying the occurrence, spread, and recurrence of the disease by administering the composition of the present invention, and "treatment" means any act of improving or beneficially changing the symptoms of the disease by administering the composition of the present invention.

[0544]

[0545] The pharmaceutical composition of the present invention can be formulated into oral or parenteral dosage forms according to standard pharmaceutical practices. These dosage forms may contain, in addition to the active ingredient, pharmaceutically acceptable additives such as carriers, adjuvants, or diluents.

[0546]

[0547] Suitable carriers include, but are not limited to, saline, polyethylene glycol, ethanol, vegetable oils, and isopropyl myristate, and diluents include, but are not limited to, lactose, dextrose, sucrose, mannitol, sorbitol, cellulose, and / or glycine. In addition, the compounds of the present invention can be dissolved in oils, propylene glycol, or other solvents commonly used in the preparation of injectable solutions. In addition, the compounds of the present invention can be formulated as ointments or creams for topical action.

[0548]

[0549] The preferred dosage of the compound of the present invention varies depending on the patient's condition and body weight, the severity of the disease, the form of the drug, the route of administration, and the duration of administration, but can be appropriately selected by those skilled in the art. However, for desirable effects, the compound of the present invention is preferably administered at a daily dose of 0.0001 to 100 mg / kg (body weight), preferably 0.001 to 100 mg / kg (body weight). Administration may be administered orally or parenterally once daily or in divided doses.

[0550]

[0551] Depending on the administration method, the pharmaceutical composition may contain 0.001 to 99 wt%, preferably 0.01 to 60 wt%, of the compound of the present invention.

[0552]

[0553] The pharmaceutical composition according to the present invention can be administered to mammals, including rats, mice, livestock, and humans, via various routes. Any route of administration is conceivable, including oral, rectal, intravenous, intramuscular, subcutaneous, intrauterine, or intracerebroventricular injection.

[0554]

[0555] Meanwhile, used in this specification means a bond that connects to another substituent.

[0556]

[0557] Additionally, in the present specification, the halogen group means fluoro, chloro, bromo, or iodo.

[0558]

[0559] Additionally, in the present specification, the alkyl group may be linear or branched. In one embodiment, the alkyl group has 1 to 10 carbon atoms. In another embodiment, the alkyl group has 1 to 4 carbon atoms. Specific examples of the above alkyl group include methyl, ethyl, propyl, n-propyl, isopropyl, butyl, n-butyl, isobutyl, tert-butyl, sec-butyl, 1-methylbutyl, 1-ethylbutyl, pentyl, n-pentyl, isopentyl, neopentyl, tert-pentyl, 1-ethyl-propyl, 1,1-dimethylpropyl, hexyl, n-hexyl, 1-methylpentyl, 2-methylpentyl, 4-methyl-2-pentyl, 3,3-dimethylbutyl, 2-ethylbutyl, heptyl, n-heptyl, isohexyl, 1-methylhexyl, 2-methylhexyl, 3-methylhexyl, 4-methylhexyl, 5-methylhexyl, octyl, n-octyl, tert-octyl, 1-methylheptyl, 2-ethylhexyl, Examples thereof include, but are not limited to, 2,4,4-trimethyl-1-pentyl, 2,4,4-trimethyl-2-pentyl, 2-propylpentyl, n-nonyl, 2,2-dimethylheptyl, or n-decyl. In addition, the description regarding the alkyl group may be applied to the haloalkyl group, except that at least one carbon of the alkyl group is substituted with a halogen group. In addition, the description regarding the alkyl group may be applied to the alkylene group, except that it is divalent.

[0560]

[0561] Additionally, in the present specification, the alkenyl group may be linear or branched. In one embodiment, the alkenyl group has 1 to 4 carbon atoms. Specific examples of the alkenyl group include, but are not limited to, vinyl, 1-propenyl, isopropenyl, 1-butenyl, 2-butenyl, or 3-butenyl.

[0562]

[0563] Additionally, in the present specification, the alkynyl group may be straight-chain. In one embodiment, the alkynyl group has 1 to 4 carbon atoms. Specific examples of the alkynyl group include, but are not limited to, ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 3-butynyl, or 3-butynyl.

[0564]

[0565] Additionally, in the present specification, the alkoxy group refers to an alkyl group singly bonded to oxygen, and may be linear or branched. According to one embodiment, the alkoxy group has 1 to 10 carbon atoms. According to another embodiment, the alkoxy group has 1 to 4 carbon atoms. Specific examples of the above alkoxy group include methoxy, ethoxy, propoxy, n-propoxy, isopropoxy, butoxy, n-butoxy, isobutoxy, tert-butoxy, sec-butoxy, 1-methylbutoxy, 1-ethylbutoxy, pentyloxy, n-pentyloxy, isopentyloxy, neopentyloxy, tert-pentyloxy, 1-ethyl-propoxy, 1,1-dimethylpropoxy, hexyloxy, n-hexyloxy, 1-methylpentyloxy, 2-methylpentyloxy, 4-methyl-2-pentyloxy, 3,3-dimethylbutoxy, 2-ethylbutoxy, heptyloxy, n-heptyloxy, isohexyloxy, 1-methylhexyloxy, 2-methylhexyloxy, 3-methylhexyloxy, 4-methylhexyloxy, Examples thereof include, but are not limited to, 5-methylhexyloxy, octyloxy, n-octyloxy, tert-octyloxy, 1-methylheptyloxy, 2-ethylhexyloxy, 2,4,4-trimethyl-1-pentyloxy, 2,4,4-trimethyl-2-pentyloxy, 2-propylpentyloxy, n-nonyloxy, 2,2-dimethylheptyloxy, or n-decyloxy. In addition, the description regarding the alkoxy group may be applied to the haloalkoxy group, except that at least one carbon of the alkoxy group is replaced by a halogen group.

[0566]

[0567] In addition, in the present specification, the cycloalkyl group is understood to mean a monovalent substituent derived from a saturated or unsaturated hydrocarbon ring compound that contains only carbon as a ring-forming atom and does not have aromaticity. According to one embodiment, the cycloalkyl group has 3 to 10 carbon atoms. According to another embodiment, the cycloalkyl group has 3 to 8 carbon atoms. According to yet another embodiment, the cycloalkyl group has 3 to 7 carbon atoms. Specific examples of the cycloalkyl group include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cycloheptyl, cyclooctyl, cyclononyl, or cyclodecyl.

[0568]

[0569] In addition, in the present specification, the aryl group is understood to mean a monovalent substituent derived from a monocyclic or condensed polycyclic compound having aromaticity and containing only carbon as a ring-forming atom. According to one embodiment, the aryl group has 6 to 20 carbon atoms. According to another embodiment, the aryl group has 6 to 12 carbon atoms. According to yet another embodiment, the aryl group has 6 to 10 carbon atoms. Specific examples of the monocyclic aryl group include, but are not limited to, phenyl, biphenylyl, or terphenylyl. In addition, the condensed polycyclic aryl group includes, but is not limited to, naphthyl, anthracenyl, phenanthryl, pyrenyl, perylenyl, or chrysenyl groups.

[0570]

[0571] In addition, in the present specification, the N-containing 6-membered heteroaryl is understood to mean a monovalent substituent derived from a monocyclic compound having aromaticity and containing N in addition to carbon as a ring-forming atom, but having 6 ring-forming atoms. Specific examples of the N-containing 6-membered heteroaryl include, but are not limited to, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, or tetrazinyl.

[0572]

[0573] In addition, in the present specification, the 5-membered or 6-membered heterocyclic group is understood to mean a substituent derived from a monocyclic compound having 5 or 6 ring-forming atoms, wherein the heterocyclic group further includes 1 to 3 heteroatoms selected from O, N, and S in addition to carbon as a ring-forming atom. In addition, the 5-membered or 6-membered heterocyclic group is understood to encompass all structures with or without aromaticity. Accordingly, the 5-membered or 6-membered heterocyclic group can be understood to include all heterocycles having aromaticity and hydrogenated derivatives thereof. In addition, the 5-membered or 6-membered heterocyclic group is substituted or unsubstituted with oxo (=O), and here, "substituted with oxo (=O)" means "comprising carbon (C=O) substituted with oxo (=O)" instead of carbon as a ring-forming atom. Specific examples of 5- or 6-membered heterocyclic groups containing 1 to 3 heteroatoms selected from the group consisting of N, O, and S substituted or unsubstituted with oxo (=O) include, but are not limited to, imidazole, pyrazole, thiazole, isothiazole, oxazole, isoxazole, thiadiazole, oxadiazole, pyridine, pyrimidine, pyridazine, pyrazine, triazine, tetrazine ring, or pyridin-2(1H)-one.

[0574]

[0575] The compound represented by chemical formula 1 of the present invention, or a pharmaceutically acceptable salt thereof, can be usefully used for the prevention or treatment of inflammatory diseases, autoimmune diseases, or cancer.

[0576] Hereinafter, the present invention will be described in more detail with reference to the following examples. However, the following examples are intended only to illustrate the present invention and the scope of the present invention is not limited to these examples.

[0577]

[0578] Manufacturing Example 1. Preparation of 4,6-dichloro-1-isopropyl-1H-pyrrolo[3,2-c]pyridine

[0579]

[0580] 4,6-Dichloro-1H-pyrrolo[3,2-c]pyridine (5.61 g, 30 mmol) was dissolved in DMF (60 mL), and 2-iodopropane (3.59 mL, 36 mmol) and Cs2CO3 (24 g, 75 mmol) were added. The reaction mixture was gradually heated and stirred at 60°C for 1 h. After cooling to room temperature, the mixture was diluted with ethyl acetate and washed with distilled water. The organic layer was dried over MgSO4, filtered, and concentrated. The obtained residue was purified by silica gel chromatography (0–50% dichloromethane / hexane) to afford 4,6-dichloro-1-isopropyl-1H-pyrrolo[3,2-c]pyridine (5.1 g, 74% yield) as a white solid.

[0581] 1 H NMR (500 MHz, CDCl3) δ 7.28-7.24 (m,2), 6.64 (d,J =3.0 Hz, 1H), 4.61-4.53 (m, 1H), 1.54 (d,J =7.0, 6H).; LC-MS (ESI) m / z: 229[M+H] +

[0582]

[0583] Manufacturing Example 2. Preparation of 4,6-dichloro-1-methyl-1H-pyrrolo[3,2-c]pyridine

[0584]

[0585] The target compound (82% yield, white solid) was prepared in the same manner as in Manufacturing Example 1, except that iodomethane was used instead of 2-iodopropane used in Manufacturing Example 1.

[0586] 1 H NMR (500 MHz, CDCl3) δ 7.21 (s, 1H), 7.10 (d,J= 3.2 Hz, 1H), 6.60 (d,J= 3.2 Hz, 1H), 3.78 (s, 3H).; LC-MS (ESI) m / z: 201[M+H] +

[0587]

[0588] Manufacturing Example 3. Preparation of 4,6-dichloro-1-ethyl-1H-pyrrolo[3,2-c]pyridine

[0589]

[0590] The target compound (80% yield, white solid) was prepared in the same manner as in Manufacturing Example 1, except that iodoethane was used instead of 2-iodopropane used in Manufacturing Example 1.

[0591] LC-MS (ESI) m / z: 215[M+H] +

[0592]

[0593] Manufacturing Example 4. Preparation of 4,6-dichloro-1-propyl-1H-pyrrolo[3,2-c]pyridine

[0594]

[0595] The target compound (81% yield, white solid) was prepared in the same manner as in Manufacturing Example 1, except that 1-iodopropane was used instead of 2-iodopropane used in Manufacturing Example 1.

[0596] LC-MS (ESI) m / z: 229[M+H] +

[0597]

[0598] Manufacturing Example 5. Preparation of 1-butyl-4,6-dichloro-1H-pyrrolo[3,2-c]pyridine

[0599]

[0600] The target compound (77% yield, yellow oil) was prepared in the same manner as in Manufacturing Example 1, except that 1-iodopropane was used instead of 2-iodopropane used in Manufacturing Example 1.

[0601] LC-MS (ESI) m / z: 243[M+H] +

[0602]

[0603] Manufacturing Example 6. Preparation of 4,6-dichloro-1-isobutyl-1H-pyrrolo[3,2-c]pyridine

[0604]

[0605] The target compound (84% yield, colorless oil) was prepared in the same manner as in Manufacturing Example 1, except that 1-bromo-2-methylpropane was used instead of 2-iodopropane used in Manufacturing Example 1.

[0606] LC-MS (ESI) m / z: 243[M+H] +

[0607]

[0608] Manufacturing Example 7. Preparation of (S)-1-(sec-butyl)-4,6-dichloro-1H-pyrrolo[3,2-c]pyridine

[0609]

[0610] The target compound (80% yield, colorless oil) was prepared in the same manner as in Manufacturing Example 1, except that (R)-sec-butyl 4-methylbenzenesulfonate was used instead of 2-iodopropane used in Manufacturing Example 1.

[0611] LC-MS (ESI) m / z: 243[M+H] +

[0612]

[0613] Manufacturing Example 8. Preparation of (R)-1-(sec-butyl)-4,6-dichloro-1H-pyrrolo[3,2-c]pyridine

[0614]

[0615] The target compound (86% yield, colorless oil) was prepared in the same manner as in Manufacturing Example 1, except that (S)-sec-butyl 4-methylbenzenesulfonate was used instead of 2-iodopropane used in Manufacturing Example 1.

[0616] LC-MS (ESI) m / z: 243[M+H] +

[0617]

[0618] Manufacturing Example 9. Preparation of 4,6-dichloro-1-(cyclopropylmethyl)-1H-pyrrolo[3,2-c]pyridine

[0619]

[0620] The target compound (90% yield, white solid) was prepared in the same manner as in Manufacturing Example 1, except that (bromomethyl)cyclopropane was used instead of 2-iodopropane used in Manufacturing Example 1.

[0621] LC-MS (ESI) m / z: 241[M+H] +

[0622]

[0623] Manufacturing Example 10. Preparation of 4,6-dichloro-1-(2-methylbutyl)-1H-pyrrolo[3,2-c]pyridine

[0624]

[0625] The target compound (80% yield, colorless oil) was prepared in the same manner as in Manufacturing Example 1, except that 1-bromo-2-methylbutane was used instead of 2-iodopropane used in Manufacturing Example 1.

[0626] LC-MS (ESI) m / z: 257[M+H] +

[0627]

[0628] Manufacturing Example 11. Preparation of 4,6-dichloro-1-cyclopentyl-1H-pyrrolo[3,2-c]pyridine

[0629]

[0630] The target compound (30% yield, white solid) was prepared in the same manner as in Manufacturing Example 1, except that bromocyclopentane was used instead of 2-iodopropane used in Manufacturing Example 1.

[0631] LC-MS (ESI) m / z: 255[M+H] +

[0632]

[0633] Manufacturing Example 12. Preparation of 4,6-dichloro-1-(cyclobutylmethyl)-1H-pyrrolo[3,2-c]pyridine

[0634]

[0635] The target compound (30% yield, yellow solid) was prepared in the same manner as in Manufacturing Example 1, except that (bromomethyl)cyclobutane was used instead of 2-iodopropane used in Manufacturing Example 1.

[0636] LC-MS (ESI) m / z: 255[M+H] +

[0637]

[0638] Manufacturing Example 13. Preparation of 4,6-dichloro-1-(cyclopentylmethyl)-1H-pyrrolo[3,2-c]pyridine

[0639]

[0640] The target compound (69% yield, white solid) was prepared in the same manner as in Manufacturing Example 1, except that (bromomethyl)cyclopentane was used instead of 2-iodopropane used in Manufacturing Example 1.

[0641] LC-MS (ESI) m / z: 269 [M+H] +

[0642]

[0643] Manufacturing Example 14. Preparation of 4,6-dichloro-1-((tetrahydrofuran-3-yl)methyl)-1H-pyrrolo[3,2-c]pyridine

[0644]

[0645] The target compound (48% yield, yellow solid) was prepared in the same manner as in Manufacturing Example 1, except that 3-(bromomethyl)tetrahydrofuran was used instead of 2-iodopropane used in Manufacturing Example 1.

[0646] LC-MS (ESI) m / z: 271[M+H] +

[0647]

[0648] Manufacturing Example 15. Preparation of 4,6-dichloro-1-(3,3-dimethylbutyl)-1H-pyrrolo[3,2-c]pyridine

[0649]

[0650] The target compound (88% yield, yellow solid) was prepared in the same manner as in Manufacturing Example 1, except that 1-bromo-3,3-dimethylbutane was used instead of 2-iodopropane used in Manufacturing Example 1.

[0651] LC-MS (ESI) m / z: 271[M+H] +

[0652]

[0653] Manufacturing Example 16. Preparation of 4,6-dichloro-1-(cyclohexylmethyl)-1H-pyrrolo[3,2-c]pyridine

[0654]

[0655] The target compound (73% yield, white solid) was prepared in the same manner as in Manufacturing Example 1, except that (bromomethyl)cyclohexane was used instead of 2-iodopropane used in Manufacturing Example 1.

[0656] LC-MS (ESI) m / z: 283[M+H] +

[0657]

[0658] Manufacturing Example 17. Preparation of 4,6-dichloro-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrrolo[3,2-c]pyridine

[0659]

[0660] The target compound (51% yield, white solid) was prepared in the same manner as in Manufacturing Example 1, except that 4-(bromomethyl)tetrahydro-2H-pyran was used instead of 2-iodopropane used in Manufacturing Example 1.

[0661] LC-MS (ESI) m / z: 285[M+H] +

[0662]

[0663] Manufacturing Example 18. Preparation of 4,6-dichloro-1-(2-methoxyethyl)-1H-pyrrolo[3,2-c]pyridine

[0664]

[0665] The target compound (80% yield, yellow solid) was prepared in the same manner as in Manufacturing Example 1, except that 1-bromo-2-methoxyethane was used instead of 2-iodopropane used in Manufacturing Example 1.

[0666] LC-MS (ESI) m / z: 245[M+H] +

[0667]

[0668] Manufacturing Example 19. Preparation of 1-benzyl-4,6-dichloro-1H-pyrrolo[3,2-c]pyridine

[0669]

[0670] The target compound (67% yield, yellow syrup) was prepared in the same manner as in Manufacturing Example 1, except that (chloromethyl)benzene was used instead of 2-iodopropane used in Manufacturing Example 1.

[0671] LC-MS (ESI) m / z: 277[M+H] +

[0672]

[0673] Manufacturing Example 20. Preparation of 4,6-dichloro-1-phenethyl-1H-pyrrolo[3,2-c]pyridine

[0674]

[0675] The target compound (77% yield, colorless syrup) was prepared in the same manner as in Manufacturing Example 1, except that (2-chloroethyl)benzene was used instead of 2-iodopropane used in Manufacturing Example 1.

[0676] LC-MS (ESI) m / z: 291[M+H] +

[0677]

[0678] Manufacturing Example 21. Preparation of 4,6-dichloro-1-(difluoromethyl)-1H-pyrrolo[3,2-c]pyridine

[0679]

[0680] The target compound (30% yield, white solid) was prepared in the same manner as in Manufacturing Example 1, except that methyl 2-chloro-2,2-difluoroacetate was used instead of 2-iodopropane used in Manufacturing Example 1.

[0681] LC-MS (ESI) m / z: 237[M+H] +

[0682]

[0683] Manufacturing Example 22. Preparation of 4,6-dichloro-1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-c]pyridine

[0684]

[0685] The target compound (85% yield, white solid) was prepared in the same manner as in Manufacturing Example 1, except that 2,2,2-trifluoroethyl trifluoromethanesulfonate was used instead of 2-iodopropane used in Manufacturing Example 1.

[0686] LC-MS (ESI) m / z: 269[M+H] +

[0687]

[0688] Manufacturing Example 23. Preparation of 4,6-dichloro-1-(2,2-difluoroethyl)-1H-pyrrolo[3,2-c]pyridine

[0689]

[0690] The target compound (93% yield, white solid) was prepared in the same manner as in Manufacturing Example 1, except that 2-bromo-1,1-difluoroethane was used instead of 2-iodopropane used in Manufacturing Example 1.

[0691] LC-MS (ESI) m / z: 251[M+H] +

[0692]

[0693] Manufacturing Example 24. Preparation of 4,6-dichloro-1-(2,2-difluorocyclopropyl)-1H-pyrrolo[3,2-c]pyridine

[0694]

[0695] The target compound (76% yield, yellow solid) was prepared in the same manner as in Manufacturing Example 1, except that 2-bromo-1,1-difluorocyclopropane was used instead of 2-iodopropane used in Manufacturing Example 1.

[0696] LC-MS (ESI) m / z: 263[M+H] +

[0697]

[0698] Manufacturing Example 25. Preparation of (R)-4,6-dichloro-1-(1,1,1-trifluoropropan-2-yl)-1H-pyrrolo[3,2-c]pyridine

[0699]

[0700] The target compound (39% yield, white solid) was prepared in the same manner as in Manufacturing Example 1, except that (S)-1,1,1-trifluoropropan-2-yl trifluoromethanesulfonate was used instead of 2-iodopropane used in Manufacturing Example 1.

[0701] LC-MS (ESI) m / z: 283[M+H] +

[0702]

[0703] Manufacturing Example 26. Preparation of 4,6-dichloro-1-((1-(trifluoromethyl)cyclopropyl)methyl)-1H-pyrrolo[3,2-c]pyridine

[0704]

[0705] The target compound (48% yield, white solid) was prepared in the same manner as in Manufacturing Example 1, except that 1-(bromomethyl)-1-(trifluoromethyl)cyclopropane was used instead of 2-iodopropane used in Manufacturing Example 1.

[0706] LC-MS (ESI) m / z: 309[M+H] +

[0707]

[0708] Manufacturing Example 27. Preparation of 4,6-dichloro-1-((4,4-difluorocyclohexyl)methyl)-1H-pyrrolo[3,2-c]pyridine

[0709]

[0710] The target compound (59% yield, white solid) was prepared in the same manner as in Manufacturing Example 1, except that 4-(bromomethyl)-1,1-difluorocyclohexane was used instead of 2-iodopropane used in Manufacturing Example 1.

[0711] LC-MS (ESI) m / z: 319[M+H] +

[0712]

[0713] Manufacturing Example 28. Preparation of 2-(4,6-dichloro-1H-pyrrolo[3,2-c]pyridin-1-yl)-2-methylpropanenitrile

[0714]

[0715]

[0716] Step 1. Preparation of 2-(4,6-dichloro-1H-pyrrolo[3,2-c]pyridin-1-yl)acetonitrile

[0717] 4,6-Dichloro-1H-pyrrolo[3,2-c]pyridine (2.0 g, 10.7 mmol) was dissolved in DMF (20 mL), and 2-bromoacetonitrile (0.89 mL, 12.4 mmol) and Cs2CO3 (5.23 g, 16.0 mmol) were added. The reaction mixture was gradually heated and stirred at 60°C for 1 h. The mixture was cooled to room temperature, diluted with ethyl acetate, and washed with distilled water. The organic layer was dried over MgSO4, filtered, and concentrated, and the resulting residue was purified by silica gel chromatography (0-50% ethyl acetate / hexane) to synthesize 2-(4,6-dichloro-1H-pyrrolo[3,2-c]pyridin-1-yl)acetonitrile (1.78 g, 74% yield) as a light brown solid.

[0718] 1 H NMR (500 MHz, DMSO-d6) δ 7.96 (s, 1H), 7.74 (d,J= 3.4 Hz, 1H), 6.73 (d,J= 3.2 Hz, 1H), 5.60 (s, 2H).;LC-MS (ESI)m / z: 226[M+H] +

[0719]

[0720] Step 2. Preparation of 2-(4,6-dichloro-1H-pyrrolo[3,2-c]pyridin-1-yl)-2-methylpropanenitrile

[0721] 2-(4,6-Dichloro-1H-pyrrolo[3,2-c]pyridin-1-yl)acetonitrile (1.78 g, 7.9 mmol) prepared in Step 1 above was dissolved in DMF (20 mL), and 60% NaH (0.79 g, 19.8 mmol) was slowly added at 0°C. The reaction mixture was stirred at 0°C for 5 minutes, after which MeI (1.5 mL, 24 mmol) was slowly added, and the mixture was reacted at room temperature for 30 minutes. The reaction mixture was neutralized by adding 1 M HCl aqueous solution, diluted with ethyl acetate, and washed with distilled water. The organic layer was dried over MgSO4, filtered, concentrated, and the resulting residue was purified by silica gel chromatography (20-30% ethyl acetate / hexane) to obtain the target compound (1.0 g, 50% yield) as a pale white solid.

[0722] 1 H NMR (500 MHz, CDCl3) δ 7.62 (s, 1H), 7.27 (d,J= 3.6 Hz, 1H), 6.70 (d,J= 3.4 Hz, 1H), 2.09 (s, 7H).; LC-MS (ESI) m / z: 226[M+H] +

[0723]

[0724] Manufacturing Example 29. Preparation of 4,6-dichloro-1-isopentyl-1H-pyrrolo[3,2-c]pyridine

[0725]

[0726] The target compound (73% yield, yellow solid) was prepared in the same manner as in Manufacturing Example 1, except that 1-bromo-3-methylbutane was used instead of 2-iodopropane used in Manufacturing Example 1.

[0727] LC-MS (ESI) m / z: 257[M+H] +

[0728]

[0729] Manufacturing Example 30. Preparation of 4,6-dichloro-1-(pyridin-2-ylmethyl)-1H-pyrrolo[3,2-c]pyridine

[0730]

[0731] The target compound (77% yield, yellow solid) was prepared in the same manner as in Manufacturing Example 1, except that 2-(chloromethyl)pyridine was used instead of 2-iodopropane used in Manufacturing Example 1.

[0732] LC-MS (ESI) m / z: 278[M+H] +

[0733]

[0734]

[0735] Manufacturing Example 31. Preparation of 1-(4,6-dichloro-1H-pyrrolo[3,2-c]pyridin-1-yl)-2-methylpropan-2-ol

[0736]

[0737] The target compound (80% yield, white solid) was prepared in the same manner as in Manufacturing Example 1, except that 2,2-dimethyloxirane was used instead of the iodopropane used in Manufacturing Example 1.

[0738] LC-MS (ESI) m / z: 259[M+H] +

[0739]

[0740] Manufacturing Example 32. Preparation of 4,6-dichloro-1-(2-fluoroethyl)-1H-pyrrolo[3,2-c]pyridine

[0741]

[0742] The target compound (72% yield, white solid) was prepared in the same manner as in Manufacturing Example 1, except that 1-fluoro-2-iodoethane was used instead of the iodopropane used in Manufacturing Example 1.

[0743] LC-MS (ESI) m / z: 233[M+H] +

[0744]

[0745] Manufacturing Example 33. Preparation of 4,6-dichloro-1-(3-fluoropropyl)-1H-pyrrolo[3,2-c]pyridine

[0746]

[0747] The target compound (78% yield, white solid) was prepared in the same manner as in Manufacturing Example 1, except that 1-iodo-3-fluoropropane was used instead of the iodopropane used in Manufacturing Example 1.

[0748] LC-MS (ESI) m / z: 247[M+H] +

[0749]

[0750] Manufacturing Example 34. Preparation of (R)-4,6-dichloro-1-(2-methylbutyl)-1H-pyrrolo[3,2-c]pyridine

[0751]

[0752] The target compound (80% yield, colorless oil) was prepared in the same manner as in Manufacturing Example 1, except that (2R)-1-bromo-2-methylbutane was used instead of 2-iodopropane used in Manufacturing Example 1.

[0753] LC-MS (ESI) m / z: 257[M+H] +

[0754]

[0755] Manufacturing Example 35. Preparation of (S)-4,6-dichloro-1-(2-methylbutyl)-1H-pyrrolo[3,2-c]pyridine

[0756]

[0757] The target compound (80% yield, colorless oil) was prepared in the same manner as in Manufacturing Example 1, except that (2S)-1-bromo-2-methylbutane was used instead of 2-iodopropane used in Manufacturing Example 1.

[0758] LC-MS (ESI) m / z: 257[M+H] +

[0759]

[0760] Example 1. Preparation of 1-(4-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one

[0761]

[0762] Step 1. Preparation of tert-butyl 4-(6-chloro-1-methyl-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridine-1(2H)-carboxylate

[0763] 4,6-Dichloro-1-methyl-1H-pyrrolo[3,2-c]pyridine (201 mg, 1.0 mmol) was dissolved in 1,4-dioxane (3.0 mL). tert-Butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (371 mg, 1.2 mmol), Pd(PPh3)4 (116 mg, 0.10 mmol), and 1 M Na2CO3 aqueous solution (2.0 mL) were added at room temperature. The reaction mixture was gradually heated and stirred at 80°C for 1 h. After cooling to room temperature, the mixture was diluted with ethyl acetate and washed with distilled water. The organic layer was dried over MgSO4, filtered, and concentrated, and the resulting residue was purified by silica gel chromatography (0-40% ethyl acetate / hexane) to synthesize tert-butyl 4-(6-chloro-1-methyl-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridine-1(2H)-carboxylate (238 mg, 68% yield) as a white solid.

[0764] 1H NMR (500 MHz, CDCl3) δ 7.15 (s, 1H), 7.07 (d,J= 3.2 Hz, 1H), 6.67 (d,J= 3.0 Hz, 1H), 6.48 (br s, 1H), 4.17 (br s, 2H), 3.76 (s, 3H), 3.67 (br s, 2H), 2.80 (br s, 2H), 1.50 (s, 9H).; LC-MS (ESI) m / z: 348[M+H] +

[0765]

[0766] Step 2. Preparation of tert-butyl 4-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridine-1(2H)-carboxylate

[0767] tert-Butyl 4-(6-chloro-1-methyl-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridine-1(2H)-carboxylate (235 mg, 0.68 mmol) was dissolved in 1,4-dioxane (4.0 mL), and 5-methylthiazol-2-amine (117 mg, 1.0 mmol), Pd2(dba)3 (62 mg), Xantphos (79 mg), and Cs2CO3 (553 mg) were added at room temperature. The reaction mixture was reacted at 160°C for 2 h using a microwave reactor. The mixture was diluted with ethyl acetate, washed with distilled water, and the organic layer was dried over MgSO4, filtered, concentrated, and the obtained residue was purified by silica gel chromatography (0-70% ethyl acetate / hexane) to synthesize tert-butyl 4-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridine-1(2H)-carboxylate (30 mg, 10% yield) as a yellow solid.

[0768] 1H NMR (500 MHz, CDCl3) δ 8.92 (br s, 1H), 7.01 (d,J= 1.0 Hz, 1H), 6.96 (d,J= 3.3 Hz, 1H), 6.68 (br s, 1H), 6.63 (d,J= 3.1 Hz, 1H), 6.56 (m, 1H), 4.21 (br s, 2H), 3.74 (br s, 2H), 3.72 (s, 3H), 2.95 (br s, 2H), 2.41 (s, 3H), 1.52 (s, 9H).; LC-MS (ESI) m / z: 426 [M+H] +

[0769]

[0770] Step 3. Preparation of 1-(4-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one

[0771] tert-Butyl 4-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridine-1(2H)-carboxylate (30 mg, 0.070 mmol) was dissolved in CH2Cl2 (3.0 mL), TFA (2.0 mL) was added, and the mixture was stirred at room temperature for 1 h. After the reaction was completed, the mixture was concentrated under reduced pressure to synthesize a salt compound. The obtained salt compound was dissolved in water (2.0 mL) and THF (4.0 mL), NaHCO3 (60 mg, 0.72 mmol) was added, and the mixture was stirred at room temperature for 10 min. After the mixture was cooled to 0°C, 1.0 M acryloyl chloride (0.091 mL, 1.3 eq) diluted in THF was slowly added dropwise. The reaction mixture was stirred at room temperature for 30 minutes, diluted with dichloromethane, and washed with distilled water and brine. The organic layer was dried over MgSO4, filtered, and concentrated, and the obtained residue was purified by silica gel chromatography (0–10% methanol / dichloromethane) to afford 1-(4-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one (14 mg, 52% yield) as a white solid.

[0772] 1 H NMR (500 MHz, DMSO-d6) δ 10.66 (s, 1H), 7.29 (d, J= 2.9 Hz, 1H), 6.96 (s, 1H), 6.89 (m, 1H), 687 (s, 1H), 6.65 (m, 1H), 6.61 (br s, 1H), 6.17 (dd,J= 16.7, 4.9 Hz, 1H), 5.73 (m, 1H), 4.35 (d,J= 52.5 Hz, 2H), 3.84 (dt,J= 17.8, 5.2 Hz, 2H), 3.68 (s, 3H), 2.89 (d,J=37.3 Hz, 2H), 2.31 (s, 3H).; LC-MS (ESI) m / z: 380 [M+H] +

[0773]

[0774] Examples 2 to 49 were prepared in a similar manner to Example 1, and the structures and analysis results of the compounds are summarized and shown in Table 1 below.

[0775]

[0776] Example structural compound name 1 H NMR;LC-MS (ESI) m / z2 1-(4-(1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO-d6) δ 10.59 (s, 1H), 7.46 (d,J= 3.1 Hz, 1H), 7.00-6.80 (m, 3H), 6.69 (m, 1H), 6.59 (br s, 1H), 6.17 (dd,J= 16.6, 4.8 Hz, 1H), 5.73 (m, 1H), 4.52 (m, 1H), 4.35 (d,J= 53.1 Hz, 2H), 3.84 (dt,J= 18.9, 5.4 Hz, 2H), 2.88 (d,J= 37.3 Hz, 2H), 2.31 (s, 3H), 1.44 (d,J= 6.6 Hz, 6H).;408 [M+H] + 3 1-(3-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-2,5-dihydro-1H-pyrrol-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO-d6) δ 10.78 (d,J= 8.7 Hz, 1H), 7.39 (m, 1H), 6.99 (s, 1H), 6.93 (d,J= 15.4 Hz, 1H), 6.90-6.64 (m, 3H)., 5.13 (s, 1H), 4.89 (s, 1H), 4.72 (s, 1H), 4.50 (s, 1H), 3.71 (s, 3H), 2.34 (d,J= 8.0 Hz, 3H).;366 [M+H] + 4 1-(4-(1-(cyclopropylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 7.12 (d,J= 3.3 Hz, 1H), 7.06 (d,J= 1.0 Hz, 1H), 6.80- 6.54 (m, 4H), 6.37 (dd,J= 16.7, 6.6 Hz, 1H), 5.74 (dd,J= 10.6, 1.0 Hz, 1H), 4.40 (d,J= 33.9 Hz, 2H), 3.99 (t,J= 5.3 Hz, 1H), 3.88 (d,J= 6.8 Hz, 3H), 3.02 (d,J= 12.7 Hz, 2H), 2.42 (s, 3H), 1.27-1.22 (m, 1H), 0.69-0.59 (m, 2H), 0.36 (q,J= 5.0 Hz, 2H).; 420 [M+H] + 5 1-(4-(1-Cyclopentyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 10.54 (d,J= 14.9 Hz, 1H), 7.11-7.03 (m, 2H), 6.77-6.54 (m, 4H), 6.36 (dd,J= 16.8, 6.2 Hz, 1H), 5.74 (d,J= 10.6 Hz, 1H), 4.63 (dt,J= 13.9, 6.9 Hz, 1H), 4.43 (d,J= 1.7 Hz, 1H), 4.36 (s, 1H), 3.99 (t,J= 5.3 Hz, 1H), 3.87 (t,J= 5.4 Hz, 1H), 3.03 (d,J= 12.3 Hz, 2H), 2.41 (s, 3H), 2.24-2.15 (m, 2H), 1.96-1.75 (m, 6H).; 434 [M+H] + 6 1-(4-(1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO-d6) δ 10.55 (s, 1H), 7.32 (d,J= 2.8 Hz, 1H), 7.02-6.77 (m, 3H), 6.64 (d,J= 27.4 Hz, 2H), 6.17 (dd,J= 3, 4.2 Hz, 1H), 5.73 (d,J= 10.1 Hz, 1H), 4.36 (d,J= 51.6 Hz, 2H), 3.85 (dd,J= 15.6, 6.3 Hz, 4H), 2.89 (d,J= 37.3 Hz, 2H), 2.31 (s, 3H), 2.11 (dt,J= 13.6, 6.7 Hz, 1H), 0.85 (d,J= 6.6 Hz, 6H).; 422 [M+H] + 7 1-(4-(1-(cyclobutylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 7.03-6.97 (m, 2H), 6.77-6.60 (m, 2H), 6.58 (d,J= 17.7 Hz, 2H), 6.37 (dd,J= 16.8, 7.1 Hz, 1H), 5.75 (dd,J= 10.6, 1.3 Hz, 1H), 4.41 (d,J= 30.9 Hz, 2H), 4.01 (dd,J= 16.2, 6.3 Hz, 3H), 3.88 (t,J= 5.5 Hz, 1H), 3.02 (d,J= 11.0 Hz, 2H), 2.40 (s, 3H), 2.08- 2.05 (m, 1H), 1.97-1.75 (m, 6H).; 434 [M+H]+8 1-(4-(6-((5-methylthiazol-2-yl)amino)-1-((tetrahydrofuran-3-yl)methyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one1 H NMR (500 MHz, CDCl3) δ 9.29 (s, 1H), 7.06-6.94 (m, 2H), 6.76-6.53 (m, 4H), 6.37 (dd,J= 16.7, 7.2 Hz, 1H), 5.75 (d,J= 10.6 Hz, 1H), 4.41 (d,J= 32.1 Hz, 2H), 4.03-3.95 (m, 4H), 3.90-3.85 (m, 1H), 3.82-3.67 (m, 3H), 3.61 (dd,J= 8.9, 4.4 Hz, 1H), 3.03 (s, 2H), 2.41 (s, 3H), 2.06-1.98 (m, 2H).; 450 [M+H] + 9 1-(4-(1-(cyclohexylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO-d6) δ 10.52 (s, 1H), 7.30 (d,J= 2.9 Hz, 1H), 6.94 (dd,J= 18.1, 10.1 Hz, 3H), 6.63 (d,J= 24.8 Hz, 2H), 6.17 (dd,J= 16.6, 4.1 Hz, 1H), 5.73 (d,J= 10.3 Hz, 1H), 4.35 (d,J= 51.9 Hz, 2H), 3.9-3..84 (m, 4H), 2.89 (d,J= 37.1 Hz, 2H), 2.31 (s, 3H), 1.70-1.40 (m, 7H), 1.14 (t,J= 9.6 Hz, 4H).; 462 [M+H]+10 1-(4-(1-(cyclopentylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one 1H NMR (500 MHz, DMSO-d6) δ 10.55 (s, 1H), 7.37 (s, 1H), 6.95 (d,J= 7.6 Hz, 3H), 6.64 (d,J= 27.0 Hz, 2H), 6.18 (d,J= 16.3 Hz, 1H), 5.74 (d,J= 9.7 Hz, 1H), 4.41 (s, 1H), 4.31 (s, 1H), 3.97 (d,J= 7.4 Hz, 2H), 3.85 (d,J= 18.7 Hz, 2H), 2.90 (d,J= 38.2 Hz, 2H), 2.32 (s, 3H), 1.68-1.41 (m, 9H).; 448 [M+H] + 11 1-(4-(1-((4,4-difluorocyclohexyl)methyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 7.05-6.97 (m, 2H), 6.65 (dd,J= 40.0, 16.7 Hz, 4H), 6.40 (dd,J= 16.7, 7.1 Hz, 1H), 5.78 (d,J= 10.5 Hz, 1H), 4.44 (d,J= 31.9 Hz, 2H), 4.07-3.87 (m, 4H), 3.04 (d,J= 13.9 Hz, 2H), 2.43 (s, 3H), 2.14 (s, 1H), 1.69 (dd,J= 34.5, 13.2 Hz, 5H), 1.40 (dt,J= 21.7, 10.9 Hz, 3H).; 498 [M+H] + 12 1-(4-(1-(2,2-difluoroethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3, 6-dihydropyridin-1(2H)-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 7.04-6.96 (m, 2H), 6.78-6.52 (m, 4H), 6.37 (dd,J= 16.8, 7.7 Hz, 1H), 6.01 (tt,J= 55.0, 3.7 Hz, 1H), 5.78-5.71 (m, 1H), 4.48-4.31 (m, 4H), 4.00 (t,J= 5.2 Hz, 1H), 3.88 (t,J= 5.3 Hz, 1H), 3.01 (d,J= 14.9 Hz, 2H), 2.40 (d,J= 6.0 Hz, 3H), 2.28-2.10 (m, 1H).; 430 [M+H] + 13 (S)-1-(4-(1-(sec-butyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 9.54 (br s, 1H), 7.09 (d,J= 3.3 Hz, 1H), 7.02 (s, 1H), 6.76-6.55 (m, 4H), 6.37 (dd,J= 16.8, 7.1 Hz, 1H), 5.75 (dd,J= 10.6, 1.5 Hz, 1H), 4.47-4.34 (m, 2H), 4.26 (m, 1H), 4.03-3.85 (m, 2H), 3.03 (m, 2H), 2.40 (s, 3H), 1.85 (m, 2H), 1.50 (d,J=6.7 Hz, 3H), 0.84 (t,J= 7.4 Hz, 3H).; 422 [M+H] + 14 (R)-1-(4-(1-(sec-butyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 9.54 (br s, 1H), 7.09 (d,J= 3.3 Hz, 1H), 7.02 (s, 1H), 6.76-6.55 (m, 4H), 6.37 (dd,J= 16.8, 7.1 Hz, 1H), 5.75 (dd,J= 10.6, 1.5 Hz, 1H), 4.47-4.34 (m, 2H), 4.26 (m, 1H), 4.03-3.85 (m, 2H), 3.03 (m, 2H), 2.40 (s, 3H), 1.85 (m, 2H), 1.50 (d,J=6.7 Hz, 3H), 0.84 (t,J= 7.4 Hz, 3H).; 422 [M+H] + 15 1-(4-(1-Benzyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO-d6) δ 10.57 (s, 1H), 7.48 (d,J= 3.3 Hz, 1H), 7.33 (t,J= 7.4 Hz, 2H), 7.26 (t,J= 7.3 Hz, 1H), 7.17 (d,J= 7.2 Hz, 2H), 7.00-6.79 (m, 3H), 6.73 (m, 1H), 6.62 (m, 1H), 6.17 (m, 1H), 5.73 (m, 1H), 5.32 (s, 2H), 4.36 (d,J= 50.9 Hz, 2H), 3.84 (dt,J= 17.8, 5.5 Hz, 2H), 2.89 (d,J= 36.8 Hz, 2H), 2.31 (s, 3H).; 456 [M+H] + 16 1-(4-(6-((5-methylthiazol-2-yl)amino)-1-phenethyl-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one 1H NMR (500 MHz, DMSO-d6) δ 10.69 (s, 1H), 7.31-7.18 (m, 6H), 7.01-6.79 (m, 3H), 6.66-6.57 (m, 2H), 6.17 (m, 1H), 5.73 (m, 1H), 4.45-4.23 (m, 4H), 3.84 (dt,J= 17.9, 5.6 Hz, 2H), 3.05 (t,J= 7.4 Hz, 2H), 2.88 (d,J= 37.2 Hz, 2H), 2.32 (s, 3H).; 470 [M+H] + 17 1-(4-(6-((5-methylthiazol-2-yl)amino)-1-((1-(trifluoromethyl)cyclopropyl)methyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 10.71 (s, 1H), 7.09 (s, 1H), 6.96 (d,J= 3.3 Hz, 1H), 6.79-6.53 (m, 4H), 6.37 (dd,J= 16.7, 6.7 Hz, 1H), 5.75 (d,J= 10.6 Hz, 1H), 4.41 (d,J= 28.0 Hz, 4H), 4.00 (t,J= 5.3 Hz, 1H), 3.88 (t,J= 5.5 Hz, 1H), 3.02 (d,J= 16.7 Hz, 2H), 2.42 (s, 3H), 1.06 (t,J= 6.1 Hz, 2H), 0.65 (s, 2H).; 488 [M+H]+18 1-(4-(1-(3,3-dimethylbutyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 7.06 (s, 1H), 7.00 (d,J= 3.1 Hz, 1H), 6.77-6.54 (m, 4H), 6.37 (dd,J= 16.7, 6.9 Hz, 1H), 5.75 (d,J= 10.7 Hz, 1H), 4.41 (d,J= 31.5 Hz, 2H), 4.07-3.98 (m, 3H), 3.88 (t,J= 5.4 Hz, 1H), 3.03 (d,J= 13.8 Hz, 2H), 2.40 (s, 3H), 1.70 (dd,J= 7.5, 4.3 Hz, 2H), 1.03 (s, 9H).; 450 [M+H] + 19 1-(4-(6-((5-methylthiazol-2-yl)amino)-1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 9.32 (s, 1H), 7.03 (s, 1H), 6.88-6.52 (m, 2H), 6.38 (dd,J= 16.7, 8.5 Hz, 1H), 5.76 (d,J= 10.5 Hz, 1H), 4.57 (dd,J= 16.7, 8.3 Hz, 1H), 4.42 (d,J= 32.1 Hz, 1H), 3.95 (dt,J= 58.8, 5.3 Hz, 1H), 3.01 (d,J= 16.4 Hz, 1H), 2.42 (d,J= 3.0 Hz, 2H).; 448 [M+H] + 20 1-(4-(1-(2,2-difluorocyclopropyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 9.92 (s, 1H), 7.10 (s, 1H), 7.02 (s, 1H), 6.90-6.52 (m, 4H), 6.38 (dd,J= 16.4, 7.4 Hz, 1H), 5.76 (d,J= 10.5 Hz, 1H), 4.42 (d,J= 31.8 Hz, 4H), 4.09-3.78 (m, 3H), 3.02 (d,J= 16.5 Hz, 1H), 2.43 (s, 3H), 2.30-1.90(m, 2H).; 442 [M+H] + 21 1-(4-(1-(difluoromethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO-d6)δ 10.88 (s, 1H), 7.89 (t,J= 59.4 Hz, 1H), 7.55 (d,J= 3.3 Hz, 1H), 7.18 (s, 1H), 7.03-6.77 (m, 3H), 6.58 (s, 1H), 6.18 (dd,J= 16.7, 4.3 Hz, 1H), 5.74 (dd,J= 11.2, 4.4 Hz, 1H), 4.36 (d,J= 51.4 Hz, 2H), 3.85 (dt,J= 18.3, 5.3 Hz, 2H), 2.88 (d,J=38.3 Hz, 2H), 2.33 (s, 3H).; 416 [M+H] + 22 2-(4-(1-Acryloyl-1,2,3,6-tetrahydropyridin-4-yl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-1-yl)-2-methylpropanenitrile 1H NMR (500 MHz, DMSO-d6) δ 10.74 (s, 1H), 7.45 (d,J= 3.1 Hz, 1H), 7.32 (s, 1H), 7.01-6.75 (m, 3H), 6.57 (s, 1H), 6.18 (dd,J= 16.7, 4.9 Hz, 1H), 5.77-5.70 (m, 1H), 4.37 (d,J= 50.9 Hz, 2H), 3.85 (dt,J= 19.0, 5.4 Hz, 2H), 2.88 (d,J= 37.9 Hz, 2H), 2.33 (s, 3H), 2.04 (s, 6H).; 433 [M+H] + 23 2-(4-(1-Acryloyl-1,2,5,6-tetrahydropyridin-3-yl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-1-yl)-2-methylpropanenitrileRotamer(major) 1 H NMR (500 MHz, DMSO-d6) δ 10.82 (s, 1H), 7.47 (m, 1H), 7.32 (s, 1H), 7.06-6.88 (m, 2H), 6.81-6.61 (m, 2H), 6.18 (dd,J= 22.8, 16.8 Hz, 1H), 5.74 (m, 1H), 4.81 (d,J= 27.9 Hz, 2H), 3.78 (dt,J= 15.8, 5.4 Hz, 2H), 2.50-2.38 (m, 2H), 2.35 (s, 3H), 2.05 (s, 6H).; 433 [M+H] + 24 (R)-1-(4-(6-((5-methylthiazol-2-yl)amino)-1-(1,1,1-trifluoropropan-2-yl)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 7.14 (d,J= 3.3 Hz, 1H), 7.04 (s, 1H), 6.81-6.51 (m, 4H), 6.38 (dd,J= 16.6, 7.6 Hz, 1H), 5.76 (dd,J= 10.5, 1.4 Hz, 1H), 4.84 (m, 1H), 4.41 (d,J= 32.7 Hz, 2H), 4.05-3.83 (m, 2H), 3.10-2.90 (m, 2H), 2.41 (s, 3H), 1.78 (d,J= 7.1 Hz, 3H).; 462 [M+H] + 25 1-(4-(1-(2,2-difluoroethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3-methyl-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 10.00 (s, 1H), 7.06 (d,J= 0.8 Hz, 1H), 7.00 (d,J= 3.3 Hz, 1H), 6.77-6.62 (m, 3H), 6.35 (dd,J= 43.0, 27.4 Hz, 2H), 6.15-5.89 (m, 1H), 5.75 (d,J= 10.5 Hz, 1H), 4.37 (td,J= 14.1, 3.7 Hz, 2H), 3.94 (dt,J= 21.7, 7.0 Hz, 1H), 3.84-3.64 (m, 2H), 2.41 (s, 3H), 1.79 (ddd,J= 18.8, 13.4, 7.1 Hz, 1H), 1.05 (s, 3H).; 444 [M+H] + 26 1-(4-(1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-2,3,6,7-tetrahydro-1H-azepin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 9.14 (br s, 1H), 7.14-7.09 (m, 1H), 6.99 (s, 1H), 6.75-6.49 (m, 4H), 6.35 (d,J= 18.1 Hz, 1H), 5.70 (d,J= 9.1 Hz, 1H), 4.59-4.49 (m, 1H), 4.41 (d,J= 5.2 Hz, 1H), 4.29 (d,J= 5.1 Hz, 1H), 3.95 (t,J= 6.0 Hz, 1H), 3.85 (t,J= 5.9 Hz, 1H), 3.14-3.02 (m, 2H), 2.38 (s, 3H), 2.18-2.05 (m, 2H), 1.51 (d,J= 6.4 Hz, 6H).; 422 [M+H] + 27 1-(7-(1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3-oxa-9-azabicyclo[3.3.1]non-6-en-9-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 9.08 (br s, 1H), 7.13 (t,J= 3.5 Hz, 1H), 7.00 (s, 1H), 6.75 (s, 1H), 6.70-6.57 (m, 3H), 6.38 (ddd,J= 16.7, 12.8, 1.4 Hz, 1H), 5.77 (d,J= 10.5 Hz, 2H), 5.34 (d,J= 5.0 Hz, 0.6H), 5.04 (d,J= 6.6 Hz, 0.4H), 4.66 (d,J = 4.8 Hz, 0.4H), 4.55 (m, 2H), 4.38 (d,J= 6.3 Hz, 0.6H), 4.08-4.01 (m, 1H), 3.91-3.73 (m, 3H), 3.43-3.09 (m, 2H), 2.40 (s, 1H), 2.38 (s, 2H), 1.57-1.45 (m, 6H).; 450 [M+H] + 28 1-(3-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-8-azabicyclo[3.2.1]oct-2-en-8-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO-d6) δ 10.65 (s, 1H), 7.29 (d,J= 3.2 Hz, 1H), 6.96 (s, 1H), 6.91-6.75 (m, 3H), 6.58 (d,J= 3.1 Hz, 1H), 6.18 (td,J= 16.5, 2.2 Hz, 1H), 5.70 (ddd,J= 15.6, 10.3, 2.2 Hz, 1H), 4.93 (dd,J= 10.6, 5.2 Hz, 1H), 4.84 (dd,J= 11.9, 7.3 Hz, 1H), 3.67 (s, 3H), 3.17 (t,J= 18.8 Hz, 1H), 2.90-2.79 (m, 1H), 2.31 (s, 3H), 2.21-1.71 (m, 4H).; 406 [M+H] + 29 1-(3-(1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-8-azabicyclo[3.2.1]oct-2-en-8-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO-d6) δ 10.57 (s, 1H), 7.44 (d,J= 3.0 Hz, 1H), 6.99-6.75 (m, 4H), 6.61 (d,J= 3.3 Hz, 1H), 6.18 (td,J= 16.8, 2.2 Hz, 1H), 5.70 (ddd,J= 15.4, 10.3, 2.2 Hz, 1H), 4.93 (dd,J= 9.9, 4.9 Hz, 1H), 4.87-4.81 (m, 1H), 4.50 (m, 1H), 3.24-3.09 (m, 1H), 2.89-2.77 (m, 1H), 2.32 (s, 3H), 2.22-1.70 (m, 4H).; 434 [M+H] + 30 1-(3-(6-((5-methylthiazol-2-yl)amino)-1-((1-(trifluoromethyl)cyclopropyl)methyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)-8-azabicyclo[3.2.1]oct-2-en-8-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO-d6) δ 7.36 (d,J= 2.8 Hz, 1H), 6.99-6.94 (m, 2H), 6.90-6.75 (m, 2H), 6.64 (d,J= 3.3 Hz, 1H), 6.18 (td,J= 16.6, 2.2 Hz, 1H), 5.70 (ddd,J= 15.0, 10.3, 2.2 Hz, 1H), 4.93 (dd, J = 10.2, 5.1 Hz, 1H), 4.85 (d,J= 6.3 Hz, 1H), 4.34 (s, 2H), 3.17 (dd,J= 23.9, 18.1 Hz, 1H), 2.84 (dd,J= 25.8, 17.5 Hz, 1H), 2.32 (d,J= 7.7 Hz, 3H), 2.17-1.74 (m, 4H), 1.04 (s, 4H).; 514 [M+H] + 31 1-(3-(1-(2,2-difluorocyclopropyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-8-azabicyclo[3.2.1]oct-2-en-8-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO-d6) δ 10.73 (s, 1H), 7.33 (d,J= 3.4 Hz, 1H), 7.04-6.74 (m, 4H), 6.64 (d,J= 3.3 Hz, 1H), 6.19 (dt,J= 17.0, 8.7 Hz, 1H), 5.75-5.65 (m, 1H), 4.93 (dd,J= 11.1, 5.5 Hz, 1H), 4.84 (d,J= 4.6 Hz, 1H), 4.25 (dd,J= 15.6, 9.1 Hz, 1H), 3.18 (m, 1H), 2.2 (m, 1H), 2.41-2.24 (m, 5H), 2.22-2.72 (m, 4H).; 468 [M+H] + 32 1-(3-(1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-8-azabicyclo[3.2.1]oct-2-en-8-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO-d6) δ 10.52 (s, 1H), 7.32 (d,J= 3.1 Hz, 1H), 6.97-6.77 (m, 4H), 6.61 (d,J= 2.9 Hz, 1H), 6.20 (dd,J= 23.7, 9.0 Hz, 1H), 5.78-5.66 (m, 1H), 4.95-4.82 (m, 2H), 3.86 (d,J= 7.1 Hz, 2H), 3.18 (dd,J= 27.7, 14.5 Hz, 1H), 2.85 (dd,J= 24.5, 17.4 Hz, 1H), 2.32 (s, 3H), 2.12-2.06 (m, 2H), 1.97-1.77 (m, 2H), 0.86-0.84 (m, 6H).; 448 [M+H]+33 1-(3-(1-cyclopentyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-8-azabicyclo[3.2.1]oct-2-en-8-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 11.10 (s, 1H), 7.06-6.95 (m, 2H), 6.83-6.64 (m, 2H), 6.64-6.43 (m, 2H), 6.33 (dd,J= 27.0, 16.4 Hz, 1H), 5.64 (dd,J= 14.6, 11.0 Hz, 1H), 5.11 (d,J= 27.6 Hz, 1H), 4.70-4.46 (m, 2H), 3.46-2.83 (m, 2H), 2.37 (s, 3H), 2.16-2.05 (m, 4H), 1.81 (s, 6H), 1.75-1.62 (m, 2H).; 460 [M+H] + 34 1-(3-(1-(2,2-difluoroethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-8-azabicyclo[3.2.1]oct-2-en-8-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 7.00 (d,J= 2.5 Hz, 2H), 6.82-6.53 (m, 4H), 6.39 (ddd,J= 22.2, 16.8, 1.6 Hz, 1H), 5.99 (t,J= 55.0 Hz, 1H), 5.75-5.67 (m, 1H), 5.21-5.08 (m, 1H), 4.73-4.63 (m, 1H), 4.36 (td,J= 14.1, 3.3 Hz, 2H), 2.41 (d,J= 6.5 Hz, 3H), 2.29-1.89 (m, 6H).; 456 [M+H] + 35 1-(3-(6-((5-methylthiazol-2-yl)amino)-1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)-8-azabicyclo[3.2.1]oct-2-en-8-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO-d6) δ 10.72 (s, 1H), 7.35 (d,J= 3.4 Hz, 1H), 7.02-6.76 (m, 4H), 6.71 (d,J= 3.3 Hz, 1H), 6.18 (td,J= 16.7, 2.2 Hz, 1H), 5.76-5.66 (m, 1H), 5.10 (q,J= 9.1 Hz, 2H), 4.95-4.80 (m, 2H), 3.18 (t,J= 18.7 Hz, 1H), 2.82 (t,J= 18.0 Hz, 1H), 2.32 (d,J= 7.9 Hz, 3H), 2.21-1.70 (m, 4H).;474 [M+H] + 36 1-(3-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-9-azabicyclo[3.3.1]non-2-en-9-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 7.03 (s, 1H), 6.95 (d, J = 3.2 Hz, 1H), 6.74-6.62 (m, 2H), 6.57 (dd,J= 21.6, 3.1 Hz, 1H), 6.47 (m, 1H), 6.32 (d,J= 16.8 Hz, 1H), 5.70 (td, J = 16.8, 2.0 Hz, 1H), 5.50 (s, 0.55H), 5.27 (s, 0.45H), 4.82 (s, 0.45H), 4.59 (s, 0.55H), 3.70 (s, 3H), 3.35-2.85(m, 2H), 2.40 (s, 1.35H), 2.39 (s, 1.65H), 2.10 (m, 1H), 1.91-1.59 (m, 5H).; 420 [M+H] + 37 1-(3-(1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-9-azabicyclo[3.3.1]non-2-en-9-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 7.15 (d, J = 2.9 Hz, 1H), 6.99 (s, 1H), 6.78 (s, 1H), 6.72-6.57 (m, 2H), 6.48 (t, J = 5.0 Hz, 1H), 6.33 (m, 1H), 5.71 (d,J= 10.6 Hz, 1H), 5.51 (s, 0.55H), 5.27 (s, 0.45H), 4.83 (s, 0.45H), 4.62-4.51 (m, 1.55H), 3.34-2.84 (m, 2H), 2.40 (s, 1.35H), 2.39 (s, 1.65H), 2.10 (m, 1H), 1.95-1.60 (m, 7H), 1.51 (d,J= 6.4 Hz, 11H).; 448 [M+H] + 38 1-(3-(1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-9-azabicyclo[3.3.1]non-2-en-9-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 7.08-6.93 (m, 2H), 6.71-6.45 (m, 4H), 6.33 (ddd,J= 16.8, 4.4, 1.6 Hz, 1H), 5.71 (d,J= 10.9 Hz, 1H), 5.39 (d,J= 116.5 Hz, 1H), 4.72 (d,J= 115.7 Hz, 1H), 3.82 (d,J= 7.3 Hz, 2H), 3.16 (s, 1H), 2.41 (d,J= 6.2 Hz, 3H), 2.26-1.97 (m, 3H), 1.97-1.57 (m, 5H), 0.99-0.83 (m, 6H).; 462 [M+H] + 39 1-(3-(1-(cyclopropylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-8-azabicyclo[3.2.1]oct-2-en-8-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 11.24 (br s, 1H), 7.04 (s, 1H), 7.01 (d,J= 3.3 Hz, 1H), 6.79 (dd,J= 11.3, 5.2 Hz, 1H), 6.67-6.49 (m, 3H), 6.36 (ddd,J= 27.8, 16.8, 1.6 Hz, 1H), 5.66 (ddd,J= 18.4, 10.4, 1.6 Hz, 1H), 5.14 (m, 1H), 4.66 (m, 1H), 3.77 (d,J= 6.7 Hz, 2H), 3.50-2.85 (m, 2H), 2.40 (s, 1.5H), 2.39 (s, 1.5H), 2.34-1.82 (m, 6H), 1.13 (m, 1H), 0.58-0.51 (m, 2H), 0.30-0.23 (m, 2H).; 446 [M+H] + 40 1-(4-(6-((1H-imidazol-2-yl)amino)-1-methyl-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 6.96 (d,J= 3.3 Hz, 1H), 6.86 (s, 2H), 6.76-6.47 (m, 4H), 6.38 (d,J= 16.8 Hz, 1H), 5.77 (d,J= 10.5 Hz, 1H), 4.41 (d,J= 33.8 Hz, 2H), 4.05-3.855 (m, 2H), 3.72 (s, 3H), 2.87 (s, 2H).; 349 [M+H] + 41 1-(4-(1-Isopropyl-6-((5-methyl-1,3,4-thiadiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 7.23 (d,J= 9.0 Hz, 1H), 7.17 (d,J= 3.3 Hz, 1H), 6.78-6.52 (m, 3H), 6.41- 6.34 (m, 1H), 5.76 (d,J= 10.5 Hz, 1H), 4.71-4.63 (m, 1H), 4.45 (s, 1H), 4.39 (s, 1H), 4.01 (t,J= 5.4 Hz, 1H), 3.89 (t,J= 5.5 Hz, 1H), 3.05-2.95 (m, 2H), 2.71 (m, 3H), 1.57 (d,J= 6.7 Hz, 6H).; 409 [M+H] + 42 1-(4-(1-isopropyl-6-((4-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 8.53 (br s, 1H), 7.15 (d,J= 3.1 Hz, 1H), 6.76-6.55 (m, 4H), 6.41-6.27 (m, 2H), 5.75 (d,J= 10.6 Hz, 1H), 4.54 (m, 1H), 4.46-4.35 (m, 2H), 4.02-3.85 (m, 2H), 3.08-2.96 (m, 2H), 2.34 (s, 3H), 1.51 (d,J= 6.7 Hz, 6H).; 408 [M+H] + 43 1-(4-(1-Isopropyl-6-(pyrimidin-4-ylamino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 8.78 (s, 1H), 8.35 (d,J= 5.8 Hz, 1H), 7.78-7.52 (m, 2H), 7.24-7.16 (m, 2H), 6.73-6.45 (m, 3H), 6.36 (dd,J= 16.6, 9.0 Hz, 1H), 5.74 (dd,J= 10.6, 1.7 Hz, 1H), 4.67 (m, 1H), 4.46-4.31 (m, 2H), 3.99-3.80 (m, 2H), 2.90 (m, 2H), 1.55 (d,J= 6.7 Hz, 6H).; 389 [M+H] + 44 1-(4-(1-isopropyl-6-((6-methylpyrimidin-4-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 8.70 (s, 1H), 7.87 (m, 1H), 7.30-7.00 (m, 3H), 6.74-6.42 (m, 3H), 6.37 (dd,J= 16.6, 10.6 Hz, 1H), 5.75 (d,J= 10.6 Hz, 1H), 4.69 (m, 1H), 4.40 (m, 2H), 3.90 (m, 2H), 2.89 (m, 2H), 2.44 (s, 3H), 1.55 (d,J= 6.7 Hz, 6H).; 403 [M+H] + 45 1-(4-(1-Isopropyl-6-((6-(trifluoromethyl)pyrimidin-4-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO-d6) δ 10.58 (s, 1H), 8.83 (s, 1H), 8.26 (br s, 1H), 7.60 (s, 1H), 6.99-6.55 (m, 3H), 6.17 (dd,J= 15.7, 10.0 Hz, 1H), 5.74 (d,J= 10.3 Hz, 1H), 4.63 (m, 1H), 4.42-4.25 (m, 2H), 3.86-3.75 (m, 2H), 2.85-2.70 (m, 2H), 1.48 (d,J= 6.6 Hz, 5H).; 457 [M+H] + 46 1-(4-(1-Isopropyl-6-((6-methoxypyrimidin-4-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 8.46 (s, 1H), 7.57 (br s, 1H), 7.26-7.20 (m, 1H), 6.83-6.49 (m, 4H), 6.37 (dd,J= 16.3, 9.2 Hz, 1H), 5.76 (d,J= 11.5 Hz, 1H), 4.66 (m, 1H), 4.47-4.35 (m, 2H), 4.00-3.81 (m, 5H), 2.94-2.84 (m, 2H), 1.54 (d,J= 6.7 Hz, 6H).; 419 [M+H] + 47 1-(4-(6-((4-fluoropyridin-2-yl)amino)-1-isopropyl-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 8.20 (dd,J= 9.0, 5.8 Hz, 1H), 7.50-7.34 (m, 2H), 7.25-7.13 (m, 2H), 6.73-6.30 (m, 5H), 5.74 (dd,J= 10.6, 1.7 Hz, 1H), 4.62 (m, 1H), 4.44-4.30 (m, 2H), 3.98-3.80 (m, 2H), 2.90 (s, 2H), 1.53 (d,J= 6.7 Hz, 6H).; 406 [M+H] + 48 1-(4-(1-isopropyl-6-((4-(trifluoromethyl)pyridin-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 8.38 (d,J= 4.8 Hz, 1H), 8.05-7.25 (m, 3H), 7.18 (d,J= 3.1 Hz, 1H), 6.96 (d,J= 5.0 Hz, 1H), 6.73-6.47 (m, 3H), 6.35 (t,J= 15.1 Hz, 1H), 5.74 (d,J= 10.6 Hz, 1H), 4.62 (m, 1H), 4.45-4.30 (m, 2H), 3.98-3.79 (m, 2H), 2.95-2.85 (m, 2H), 1.54 (d,J= 6.6 Hz, 6H).; 456 [M+H] + 49 1-(4-(1-isopropyl-6-((4-methylpyridin-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 8.13 (d,J= 5.2 Hz, 1H), 7.77 (s, 1H), 7.48 (d,J= 16.1 Hz, 1H), 7.13 (d,J= 2.7 Hz, 1H), 6.99 (d,J= 19.1 Hz, 1H), 6.63 (ddd,J= 12.0, 11.4, 6.3 Hz, 3H), 6.48 (d,J= 30.6 Hz, 1H), 6.34 (t,J= 14.6 Hz, 1H), 5.72 (d,J= 10.5 Hz, 1H), 4.63 (m, 1H), 4.42-4.28 (m, 2H), 3.85 (dt,J= 71.7, 5.4 Hz, 2H), 2.89 (s, 2H), 2.27 (s, 3H), 1.51 (d,J= 6.7 Hz, 6H).; 402 [M+H] +

[0777]

[0778] Example 50. Preparation of N-(3-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide

[0779]

[0780]

[0781] Step 1. Preparation of tert-butyl (3-(6-chloro-1-methyl-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)carbamate

[0782] Except that (3-((tert-butoxycarbonyl)amino)phenyl)boronic acid was used instead of tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate used in step 1 of the above-mentioned Example 1, tert-butyl (3-(6-chloro-1-methyl-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)carbamate (52% yield) was synthesized in the same manner as step 1 of the above-mentioned Example 1.

[0783] LC-MS (ESI) m / z: 358 [M+H] +

[0784]

[0785] Step 2. Preparation of tert-butyl (3-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)carbamate

[0786] Except that tert-butyl (3-(6-chloro-1-methyl-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)carbamate was used instead of tert-butyl 4-(6-chloro-1-methyl-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)carbamate used in step 2 of the above-mentioned Example 1, tert-butyl (3-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)carbamate (27% yield) was synthesized in the same manner as in step 2 of the above-mentioned Example 1.

[0787] 1H NMR (500 MHz, CDCl3) δ 8.53 (s, 1H), 8.12 (s, 1H), 7.82 (d,J= 6.9 Hz, 1H), 7.46 (m, 2H), 7.01 (m, 2H), 6.79 (m, 2H), 6.63 (s, 1H), 3.75 (s, 3H), 2.39 (s, 3H), 1.54 (s, 9H).; LC-MS (ESI) m / z: 436 [M+H] +

[0788]

[0789] Step 3. Preparation of N-(3-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide

[0790] Except that tert-butyl 4-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridine-1(2H)-carboxylate was replaced with tert-butyl (3-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)carbamate, N-(3-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide (77% yield) was synthesized in the same manner as in step 3 of example 1, except that tert-butyl (3-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)carbamate was used instead of tert-butyl 4-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide was synthesized (77% yield).

[0791] 1H NMR (500 MHz, DMSO-d6) δ 11.28 (br s, 1H), 10.36 (s, 1H), 8.66 (s, 1H), 7.89 (d,J= 7.7 Hz, 1H), 7.66 (d,J= 7.9 Hz, 1H), 7.54 (t,J= 7.9 Hz, 1H), 7.45 (d,J= 3.2 Hz, 1H), 7.09 (s, 1H), 7.03 (s, 1H), 6.82 (d,J= 3.1 Hz, 1H), 6.50 (dd,J= 16.9, 10.1 Hz, 1H), 6.31 (dd,J= 16.9, 1.6 Hz, 1H), 5.80 (dd,J= 10.2, 1.6 Hz, 1H), 3.76 (s, 3H), 2.34 (s, 3H).; LC-MS (ESI) m / z: 390 [M+H] +

[0792]

[0793] Examples 51 to 78 were prepared in a similar manner to Example 50 above, and the structures and analysis results of the compounds are summarized and shown in Table 2 below.

[0794]

[0795] Example structural compound name 1 H NMR;LC-MS (ESI) m / z51 N-(2-fluoro-3-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide 1H NMR (500 MHz, DMSO-d6) δ 10.85 (s, 1H), 10.10 (s, 1H), 8.06 (t,J= 7.2 Hz, 1H), 7.60 (t,J= 6.8 Hz, 1H), 7.36 (t,J= 7.9 Hz, 1H), 7.33 (d,J= 3.3 Hz, 1H), 7.05 (s, 1H), 6.97 (s, 1H), 6.66 (dd,J= 17.0, 10.2 Hz, 1H), 6.36-6.29 (m, 2H), 5.80 (dd,J= 10.2, 1.7 Hz, 1H), 3.73 (s, 3H), 2.27 (s, 3H).; 408 [M+H] + 52 N-(2-methoxy-3-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide 1 H NMR (500 MHz, DMSO-d6) δ 10.90 (s, 1H), 9.68 (s, 1H), 8.22 (d,J= 8.1 Hz, 1H), 7.37 (d,J= 7.5 Hz, 1H), 7.30-7.22 (m, 2H), 7.06 (s, 1H), 6.98 (s, 1H), 6.79 (dd,J= 16.9, 10.1 Hz, 1H), 6.33-6.22 (m, 2H), 5.76 (d,J= 10.1 Hz, 1H), 3.73 (s, 3H), 3.25 (s, 3H), 2.26 (s, 3H).; 420 [M+H] + 53 N-(3-methyl-5-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide 1H NMR (500 MHz, DMSO-d6) δ 10.77 (s, 1H), 10.25 (s, 1H), 8.39 (s, 1H), 7.76 (s, 1H), 7.53 (s, 1H), 7.39 (d,J= 3.2 Hz, 1H), 6.98 (s, 2H), 6.79 (d,J= 3.2 Hz, 1H), 6.49 (dd,J= 16.9, 10.1 Hz, 1H), 6.30 (dd,J= 17.0, 1.8 Hz, 1H), 5.78 (dd,J= 10.1, 1.8 Hz, 1H), 3.73 (s, 3H), 2.43 (s, 3H), 2.32 (s, 3H).; 404 [M+H] + 54 N-(2-fluoro-5-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide 1 H NMR (500 MHz, DMSO-d6) δ 12.00 (s, 1H), 10.18 (s, 1H), 8.99 (d,J= 6.6 Hz, 1H), 7.93 (m, 1H), 7.56-7.44 (m, 2H), 7.23 (s, 1H), 7.10 (s, 1H), 6.86 (d,J= 2.9 Hz, 1H), 6.71 (dd,J= 17.0, 10.2 Hz, 1H), 6.34 (dd,J= 17.0, 1.4 Hz, 1H), 5.83 (dd,J= 10.3, 1.4 Hz, 1H), 3.79 (s, 3H), 2.37 (s, 3H).; 408 [M+H] + 55 N-(2-methyl-5-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide 1H NMR (500 MHz, DMSO-d6) δ 10.76 (s, 1H), 9.61 (s, 1H), 8.41 (s, 1H), 7.92 (dd,J= 7.9, 1.3 Hz, 1H), 7.43 (d,J= 8.0 Hz, 1H), 7.38 (d,J= 3.2 Hz, 1H), 6.98 (d,J= 1.0 Hz, 1H), 6.94 (s, 1H), 6.81 (d,J= 3.1 Hz, 1H), 6.62 (dd,J= 16.9, 10.2 Hz, 1H), 6.31 (dd,J= 17.0, 1.8 Hz, 1H), 5.79 (dd,J= 10.2, 1.7 Hz, 1H), 3.72 (s, 3H), 2.33 (s, 3H), 2.31 (s, 3H).;404 [M+H] + 56 N-(2,6-dimethyl-3-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide 1 H NMR (500 MHz, DMSO-d6) δ 12.46 (s, 1H), 10.77 (s, 1H), 9.61 (s, 1H), 7.33-7.21 (m, 3H), 6.99 (s, 1H), 6.95 (s, 1H), 6.52 (dd,J= 17.1, 10.3 Hz, 1H), 6.25 (dd,J= 17.1, 1.6 Hz, 1H), 6.07 (d,J= 3.0 Hz, 1H), 3.72 (s, 3H), 2.25 (s, 3H), 2.23 (s, 3H), 2.06 (s, 3H).; 418 [M+H] + 57 N-(2,6-difluoro-3-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide 1H NMR (500 MHz, DMSO-d6) δ 10.83 (s, 1H), 10.11 (s, 1H), 7.81 (dd,J= 14.4, 7.6 Hz, 1H), 7.40 (m, 1H), 7.34 (d,J= 3.2 Hz, 1H), 7.04 (s, 1H), 6.97 (s, 1H), 6.53 (dd,J= 17.0, 10.1 Hz, 1H), 6.35-6.28 (m, 2H), 5.84 (d,J= 11.7 Hz, 1H), 3.73 (s, 3H), 2.28 (s, 3H).; 426 [M+H] + 58 N-(3-(1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-2-methylphenyl)acrylamide 1 H NMR (500 MHz, CDCl3) δ 8.05 (s, 1H), 7.40-7.31 (m, 2H), 7.12 (d,J= 3.4 Hz, 1H), 7.02-6.95 (m, 2H), 6.48 (d,J= 16.7 Hz, 1H), 6.38-6.21 (m, 2H), 5.80 (d,J= 9.5 Hz, 1H), 4.61 (m, 1H), 2.34 (s, 3H), 2.23 (s, 3H), 1.54 (d,J= 6.7 Hz, 6H).; 432 [M+H] + 59 N-(4-fluoro-3-(1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide 1H NMR (500 MHz, DMSO-d6) δ 10.71 (s, 1H), 10.33 (s, 1H), 8.20 (dd,J= 6.4, 2.4 Hz, 1H), 7.78 (m, 1H), 7.50 (d,J= 3.4 Hz, 1H), 7.36 (t,J= 9.4 Hz, 1H), 7.12 (s, 1H), 6.96 (s, 1H), 6.45 (dd,J= 17.0, 10.1 Hz, 1H), 6.36 (t,J= 3.3 Hz, 1H), 6.27 (dd,J= 16.9, 1.6 Hz, 1H), 5.77 (m, 1H), 4.58 (m, 1H), 2.26 (s, 3H), 1.48 (d,J= 6.7 Hz, 6H).; 436 [M+H] + 60 N-(2,4-difluoro-5-(1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide 1 H NMR (500 MHz, CDCl3) δ 9.33 (br s, 1H), 8.90 (s, 1H), 7.46 (s, 1H), 7.16 (d,J= 3.4 Hz, 1H), 7.07-6.95 (m, 3H), 6.52 (t,J= 3.4 Hz, 1H), 6.46 (d,J= 16.8 Hz, 1H), 6.30 (dd,J= 16.8, 10.2 Hz, 1H), 5.80 (d,J= 10.4 Hz, 1H), 4.58 (m, 1H), 2.38 (s, 3H), 1.53 (d, J = 6.7 Hz, 6H).; 454 [M+H] + 61 N-(3-(1-(cyclopropylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-4-fluorophenyl)acrylamide 1H NMR (500 MHz, MeOD-d4)δ 8.23 ​​(dd,J= 6.3, 2.6 Hz, 1H), 7.76-7.72 (m, 1H), 7.31-7.22 (m, 2H), 7.14-6.82 (m, 3H), 6.50-6.32 (m, 3H), 5.78 (dd,J= 9.9, 1.7 Hz, 1H), 4.00 (t,J= 6.8 Hz, 2H), 2.32 (s, 3H), 1.28 (s, 1H), 0.63 (q,J= 5.6 Hz, 2H), 0.43 (d,J= 5.2 Hz, 2H).; 448 [M+H] + 62 N-(3-(1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-2-methylphenyl)acrylamide 1 H NMR (500 MHz, CDCl3) δ 9.55 (s, 1H), 8.06 (s, 1H), 7.43-7.31 (m, 2H), 6.95 (dd,J= 38.9, 35.8 Hz, 3H), 6.55-6.18 (m, 3H), 5.80 (d,J= 9.6 Hz, 1H), 3.86 (d,J= 7.3 Hz, 2H), 2.34 (s, 3H), 2.23 (d,J= 14.1 Hz, 3H), 1.83 (s, 1H), 0.95 (t,J= 12.2 Hz, 6H).; 446 [M+H] + 63 N-(4-fluoro-3-(1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide 1H NMR (500 MHz, MeOD-d4)δ 8.23 ​​(dd,J= 6.3, 2.6 Hz, 1H), 7.79-7.71 (m, 1H), 7.29-7.18 (m, 2H), 7.00 (s, 1H), 6.91 (d,J= 0.9 Hz, 1H), 6.52-6.34 (m, 3H), 5.78 (dd,J= 10.0, 1.7 Hz, 1H), 3.95 (d,J= 7.3 Hz, 2H), 2.32 (s, 3H), 2.25-2.22 (m, 1H), 0.96 (d,J= 6.6 Hz, 6H).; 450 [M+H] + 64 N-(5-(1-(cyclopropylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-2-fluorophenyl)acrylamide 1 H NMR (500 MHz, CDCl3) δ 9.16 (s, 1H), 8.01-7.92 (m, 1H), 7.28 (s, 1H), 7.19 (d,J= 3.3 Hz, 2H), 6.86 (d,J= 38.6 Hz, 4H), 6.49-6.30 (m, 2H), 5.80 (d,J= 10.2 Hz, 1H), 3.91 (d,J= 6.8 Hz, 2H), 2.34 (d,J= 10.2 Hz, 3H), 2.00 (d,J= 12.3 Hz, 1H), 0.63 (q,J= 5.4 Hz, 2H), 0.36 (q,J= 5.1 Hz, 2H).; 448 [M+H] + 65 N-(5-(1-(cyclopropylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-2-methylphenyl)acrylamide 1H NMR (500 MHz, CDCl3) δ 8.59 (s, 1H), 7.95 (s, 1H), 7.37 (d,J= 7.7 Hz, 1H), 7.17 (d,J= 3.3 Hz, 1H), 6.85 (d,J= 31.8 Hz, 3H), 6.516.26 (m, 3H), 5.77 (d,J= 9.7 Hz, 1H), 3.93-3.83 (m, 2H), 2.33 (s, 3H), 2.15 (t,J= 7.5 Hz, 3H), 0.62 (dd,J= 13.1, 5.2 Hz, 2H), 0.36 (d,J= 5.0 Hz, 2H).; 444 [M+H] + 66 N-(5-(1-(cyclopropylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-2,4-difluorophenyl)acrylamide 1 H NMR (500 MHz, CDCl3) δ 8.93 (s, 1H), 7.46 (d,J= 8.9 Hz, 1H), 7.18 (d,J= 3.3 Hz, 1H), 7.10-6.92 (m, 3H), 6.57-6.43 (m, 2H), 6.31 (dd,J= 16.8, 10.2 Hz, 1H), 5.82 (d,J= 10.4 Hz, 1H), 3.93 (d,J= 6.8 Hz, 2H), 2.36 (s, 3H), 2.27 (dd,J= 16.7, 5.4 Hz, 1H), 0.67 (q,J= 5.4 Hz, 2H), 0.39 (q,J= 5.0 Hz, 2H).; 466 [M+H] + 67 N-(2,4-difluoro-5-(1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide 1H NMR (500 MHz, CDCl3) δ 8.93 (s, 1H), 7.46-7.35 (m, 1H), 7.10-6.94 (m, 3H), 6.90 (s, 1H), 6.48 (dt,J= 36.6, 11.5 Hz, 2H), 6.37-6.23 (m, 1H), 5.82 (d,J= 10.4 Hz, 1H), 3.84 (t,J= 10.9 Hz, 2H), 2.37 (s, 3H), 2.24-2.15 (m, 1H), 0.96 (d,J= 6.6 Hz, 6H).; 468 [M+H] + 68 (S)-N-(3-(1-(sec-butyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-4-fluorophenyl)acrylamide 1 H NMR (500 MHz, CDCl3) δ 13.72 (s, 1H), 8.57 (s, 1H), 8.25 (s, 1H), 7.68 (s, 1H), 7.22-7.10 (m, 2H), 6.99 (s, 1H), 6.82 (s, 1H), 6.55-6.35 (m, 3H), 5.74 (d,J= 8.7 Hz, 1H), 4.25 (m, 1H), 2.30 (s, 3H), 1.88-1.66 (m, 2H), 1.36 (d,J= 5.2 Hz, 3H), 0.73 (t,J= 7.5 Hz, 3H).; 450 [M+H] + 69 N-(5-(1-(3,3-dimethylbutyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-2,4-difluorophenyl)acrylamide 1 H NMR (500 MHz, DMSO-d6)δ 7.63-7.55 (m, 2H), 7.28 (s, 2H), 6.70-6.23 (m, 4H), 5.85-5.76 (m, 1H), 4.22-4.14 (m, 2H), 2.37-2.30 (m, 3H), 1.70-1.64 (m, 2H), 1.03-0.97 (m, 9H).; 496 [M+H] + 70 N-(3-(1-cyclopentyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-4-fluorophenyl)acrylamide 1 H NMR (500 MHz, DMSO-d6) δ 10.73 (s, 1H), 10.34 (s, 1H), 8.20 (dd,J= 6.4, 2.4 Hz, 1H), 7.78 (m, 1H), 7.45 (d,J= 3.3 Hz, 1H), 7.36 (t,J= 9.4 Hz, 1H), 7.14 (s, 1H), 6.96 (s, 1H), 6.45 (dd,J= 16.9, 10.1 Hz, 1H), 6.35 (t,J= 3.3 Hz, 1H), 6.27 (dd,J= 16.9, 1.6 Hz, 1H), 5.77 (m, 1H), 4.73 (m, 1H), 2.26 (s, 3H), 2.21-2.12 (m, 2H), 1.95-1.80 (m, 4H), 1.80-1.66 (m, 2H).; 462 [M+H] + 71 N-(4-fluoro-3-(6-((5-methylthiazol-2-yl)amino)-1-((tetrahydrofuran-3-yl)methyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide 1 H NMR (500 MHz, CDCl3) δ 7.90 (d,J= 49.0 Hz, 2H), 7.57 (s, 1H), 7.01 (dd,J= 26.8, 5.2 Hz, 2H), 6.55-6.41 (m, 2H), 6.28 (dd,J= 16.6, 10.2 Hz, 1H), 5.79 (d,J= 10.2 Hz, 1H), 4.01 (dd,J= 17.1, 6.7 Hz, 2H), 3.80-3.55 (m, 4H), 2.82 (d,J= 6.7 Hz, 1H), 2.35 (s, 3H), 2.03 (dt,J= 14.1, 7.0 Hz, 2H).; 478 [M+H] + 72 N-(2-fluoro-5-(6-((5-methylthiazol-2-yl)amino)-1-((tetrahydrofuran-3-yl)methyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide1 H NMR (500 MHz, DMSO-d6)δ 10.18 (s, 1H), 8.93 (d,J= 6.4 Hz, 1H), 8.00-7.92 (m, 1H), 7.55-7.44 (m, 2H), 7.10-7.01 (m, 2H), 6.85 (d,J= 3.2 Hz, 1H), 6.73-6.62 (m, 1H), 6.34 (dd,J= 17.0, 1.5 Hz, 1H), 5.83 (d,J= 11.7 Hz, 2H), 4.12 (dd,J= 7.5, 3.4 Hz, 2H), 2.77 (d,J= 6.4 Hz, 1H), 2.33 (s, 3H), 2.01-1.85 (m, 4H), 1.64-1.55 (m, 2H).; 478 [M+H] + 73 N-(2-fluoro-3-(6-((5-methylthiazol-2-yl)amino)-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide 1 H NMR (500 MHz, CDCl3) δ 8.54 (s, 1H), 7.61 (d,J= 6.9 Hz, 1H), 7.32 (dd,J= 21.0, 13.1 Hz, 1H), 7.00 (d,J= 3.4 Hz, 2H), 6.91 (s, 1H), 6.55-6.21 (m, 3H), 5.82 (dd,J= 16.4, 10.7 Hz, 1H), 4.02-3.85 (m, 4H), 3.35 (t,J= 11.1 Hz, 2H), 2.39-2.29 (m, 3H), 2.14-2.08 (m, 1H), 1.57-1.37 (m, 4H).; 492 [M+H] + 74 N-(5-(1-(2,2-difluoroethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-2-methylphenyl)acrylamide 1H NMR (500 MHz, MeOD-d4)δ 8.00 (d,J= 26.0 Hz, 1H), 7.66 (d,J= 8.7 Hz, 1H), 7.38 (dd,J= 57.1, 25.8 Hz, 2H), 6.95 (d,J= 18.5 Hz, 2H), 6.61-6.46 (m, 1H), 6.46-6.01 (m, 3H), 5.86-5.77 (m, 1H), 4.57 (d,J= 9.9 Hz, 2H), 2.36 (dd,J= 20.6, 9.6 Hz, 3H), 1.29 (s, 3H).; 454 [M+H] + 75 N-(3-(1-(2,2-difluoroethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-4-fluorophenyl)acrylamide 1 H NMR (500 MHz, DMSO-d6) δ 8.39 (d,J= 4.0 Hz, 1H), 7.91 (s, 1H), 7.67 (dd,J= 8.6, 3.5 Hz, 1H), 7.58 (d,J= 3.2 Hz, 1H), 7.45-7.18 (m, 3H), 6.53-6.41 (m, 2H), 6.27 (dd,J= 17.0, 1.6 Hz, 1H), 5.82-5.71 (m, 1H), 3.88-3.77 (m, 2H), 2.28 (d,J= 19.9 Hz, 3H).; 458 [M+H]+76 N-(5-(1-(2,2-difluoroethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-2-fluorophenyl)acrylamide 1H NMR (500 MHz, CDCl3) δ 9.24 (s, 1H), 8.00-7.92 (m, 1H), 7.55 (s, 1H), 7.33-7.28 (m, 1H), 7.10 (d,J= 3.3 Hz, 1H), 6.95 (d,J= 52.5 Hz, 2H), 6.51 (d,J= 16.8 Hz, 1H), 6.34 (dd,J= 16.8, 10.2 Hz, 1H), 6.03 (t,J= 55.0 Hz, 2H), 5.85 (d,J= 10.3 Hz, 1H), 4.41 (td,J= 14.2, 3.6 Hz, 2H), 2.44-2.33 (m, 3H).;458 [M+H] + 77 N-(2,4-difluoro-5-(6-((5-methylthiazol-2-yl)amino)-1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide 1 H NMR (500 MHz, CDCl3) δ 8.93 (s, 1H), 8.76 (br s, 1H), 7.41 (s, 1H), 7.12-6.97 (m, 3H), 6.62 (t,J= 3.2 Hz, 1H), 6.48 (d,J= 16.8 Hz, 1H), 6.31 (dd,J= 16.8, 10.2 Hz, 1H), 5.83 (d,J= 10.3 Hz, 1H), 4.60 (dd,J= 16.9, 8.4 Hz, 2H), 2.37 (s, 3H).; 494 [M+H] + 78 N-(4-fluoro-3-(6-((5-methylthiazol-2-yl)amino)-1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide 1H NMR (500 MHz, DMSO-d6) δ 10.88 (s, 1H), 10.36 (s, 1H), 8.23 ​​(m, 1H), 7.80 (m, 1H), 7.42-7.35 (m, 2H), 7.17 (s, 1H), 6.98 (s, 1H), 6.45 (dd,J= 16.9, 10.1 Hz, 2H), 6.28 (d,J= 16.9 Hz, 1H), 5.78 (d,J= 10.2 Hz, 1H), 5.17 (dd,J= 18.1, 9.0 Hz, 2H), 2.27 (s, 3H).; 476 [M+H] +

[0796]

[0797] Example 79. Preparation of (S)-1-(3-((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one

[0798]

[0799]

[0800] Step 1. Preparation of tert-butyl (S)-3-((6-chloro-1-isopropyl-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidine-1-carboxylate

[0801] Tert-Butyl (S)-3-hydroxypiperidine-1-carboxylate (307 mg, 1.64 mmol) was dissolved in DMF (5.0 mL), and 60% NaH (66 mg, 1.64 mmol) was slowly added at 0°C. The reaction mixture was stirred at 0°C for 30 minutes, after which 4,6-dichloro-1-isopropyl-1H-pyrrolo[3,2-c]pyridine (250 mg, 1.09 mmol) was added and reacted at 100°C for 2 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate, and washed with aqueous ammonium chloride solution. The organic layer was dried over MgSO4, filtered, and concentrated, and the resulting residue was purified by silica gel chromatography (0-30% ethyl acetate / hexane) to synthesize tert-butyl (S)-3-((6-chloro-1-isopropyl-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidine-1-carboxylate (242 mg, 58% yield) as a white solid.

[0802] 1 H NMR (500 MHz, CDCl3) δ 7.08 (m, 1H), 6.94 (m, 1H), 6.55 (d,J= 2.8 Hz, 1H), 5.76 (d,J= 19.2 Hz, 1H), 4.51 (m, 1H), 3.77-3.47 (m, 4H), 2.20 (m, 2H), 1.54-1.43 (m, 15H).; LC-MS (ESI) m / z: 380 [M+H] +

[0803]

[0804] Step 2. Preparation of tert-butyl (S)-3-((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidine-1-carboxylate

[0805] Except that tert-butyl (S)-3-((6-chloro-1-isopropyl-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidine-1-carboxylate was used instead of tert-butyl 4-(6-chloro-1-methyl-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridine-1(2H)-carboxylate used in step 2 of the above-mentioned example 1, tert-butyl (S)-3-((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidine-1-carboxylate was used in the same manner as in step 2 of the above-mentioned example 1, to synthesize tert-butyl (S)-3-((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidine-1-carboxylate (21% yield).

[0806] LC-MS (ESI) m / z: 458 [M+H] +

[0807]

[0808] Step 3. Preparation of (S)-1-(3-((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one

[0809] In the same manner as in step 3 of the above Example 1, except that tert-butyl 4-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridine-1(2H)-carboxylate was used instead of tert-butyl (S)-3-((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidine-1-carboxylate, (S)-1-(3-((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one (69% yield) was synthesized.

[0810] 1H NMR (500 MHz, DMSO-d6)δ 10.61 (s, 1H), 7.25 (t,J= 3.0 Hz, 1H), 6.97 (s, 1H), 6.72-6.50 (m, 2H), 6.37 (s, 1H), 6.14 (ddd,J= 16.7, 5.7, 2.0 Hz, 1H), 5.90 (d,J= 42.7 Hz, 1H), 5.66 (ddd,J= 26.2, 10.3, 1.9 Hz, 1H), 4.45 (m, 1H), 4.10-3.47 (m, 4H), 2.44-2.15 (m, 5H), 1.41 (d,J= 6.6 Hz, 6H).; LC-MS (ESI) m / z: 412 [M+H] +

[0811]

[0812] Examples 80 to 204 were prepared in a similar manner to Example 79, and the structures and analysis results of the compounds are summarized and shown in Table 3 below.

[0813]

[0814] Example structural compound name 1 H NMR;LC-MS (ESI) m / z80 1-(3-((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)azetidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, DMSO-d6) δ 10.56 (s, 1H), 7.31 (d,J= 3.3 Hz, 1H), 6.97 (s, 1H), 6.75 (s, 1H), 6.46 (d,J= 3.2 Hz, 1H), 6.36 (dd,J= 17.0, 10.3 Hz, 1H), 6.13 (dd,J= 17.0, 1.9 Hz, 1H), 5.73 (dt,J= 10.0, 3.3 Hz, 1H), 5.68 (dd,J= 10.3, 1.9 Hz, 1H), 4.78 (dd,J= 9.4, 6.8 Hz, 1H), 4.54-4.42 (m, 2H), 4.25 (dd,J= 9.9, 2.8 Hz, 1H), 3.97 (dd,J= 11.2, 2.9 Hz, 1H), 2.33 (s, 3H), 1.43 (d,J= 6.6 Hz, 6H).; 398 [M+H] + 81 (S)-1-(3-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 7.90 (d,J= 49.0 Hz, 1H), 7.57 (s, 1H), 7.20 (d,J= 9.3 Hz, 1H), 7.01 (dd,J= 26.8, 5.2 Hz, 2H), 6.54-6.42 (m, 2H), 6.28 (dd,J= 16.6, 10.2 Hz, 1H), 5.79 (d,J= 10.2 Hz, 1H), 4.05-3.95 (m, 3H), 3.81-3.71 (m, 2H), 3.63 (dd,J= 8.9, 4.6 Hz, 1H), 2.82 (d,J= 6.7 Hz, 1H), 2.35 (s, 3H), 2.03 (dd,J= 13.4, 5.1 Hz, 2H), 1.26 (d,J= 10.5 Hz, 6H).; 426 [M+H]+82 (R)-1-(3-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one1 H NMR (500 MHz, CDCl3) δ 7.02 (dd,J= 7.4, 1.1 Hz, 1H), 6.83 (dd,J= 7.8, 3.2 Hz, 1H), 6.57-6.33 (m, 4H), 6.03 (dd,J= 10.4, 8.2 Hz, 1H), 5.68 (ddd,J= 24.9, 9.6, 2.6 Hz, 1H), 4.05 (dd,J= 12.0, 4.9 Hz, 1H), 3.97-3.86 (m, 2H), 3.86-3.74 (m, 4H), 2.41-2.37 (m, 3H), 2.34-2.25 (m, 1H), 2.19-2.10 (m, 1H), 0.92 (dt,J= 25.3, 12.6 Hz, 6H).; 426 [M+H] + 83 1-((3S,4R)-3-fluoro-4-((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 8.57 (s, 1H), 7.02 (m, 1H), 6.98 (s, 1H), 6.58 (m, 1H), 6.52-6.42 (m, 3H), 5.92-5.50 (m, 3H), 4.49 (m, 1H), 4.36 (m, 1H), 4.15-3.79 (m, 3H), 2.36 (s, 1H), 2.33 (s, 2H), 1.3-1.49, (m, 6H).; 430 [M+H] + 84 (S)-1-(3-((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)piperidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 8.25 (br s, 1H), 6.99-6.94 (m, 2H), 6.50-6.38 (m, 3H), 6.17 (d,J= 16.8 Hz, 1H), 5.55-5.43 (m, 2H), 4.48 (m, 1H), 3.94-3.36 (m, 4H), 2.36 (s, 3H), 2.21-1.54 (m, 4H), 1.49 (d,J= 6.7 Hz, 6H).; 426 [M+H] + 85 (S)-1-(2-(((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl )pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 9.19 (s, 1H), 6.96 (d,J= 14.5 Hz, 1H), 6.84 (d,J= 3.1 Hz, 1H), 6.57-6.32 (m, 4H), 5.65 (ddd,J= 33.0, 10.3, 1.7 Hz, 1H), 4.89-4.76 (m, 1H), 4.72-4.46 (m, 2H), 3.79 (d,J= 7.3 Hz, 2H), 3.76-3.60 (m, 2H), 2.37 (d,J= 7.2 Hz, 3H), 2.29 (dd,J= 19.5, 9.2 Hz, 1H), 2.19-1.96 (m, 6H), 0.91 (t,J= 8.3 Hz, 6H).; 440 [M+H] + 86 (S)-1-(2-(((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl )azetidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 7.07-6.98 (m, 2H), 6.65-6.18 (m, 4H), 5.66 (dd,J= 26.1, 10.3 Hz, 1H), 5.08-4.81 (m, 3H), 4.55-4.07 (m, 3H), 2.69-2.17 (m, 5H), 1.52 (d,J= 3.7 Hz, 6H).; 412 [M+H] + 87 1-((2R,4S)-4-((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-2-methylpyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 7.06-6.97 (m, 2H), 6.58-6.33 (m, 4H), 6.07-5.95 (m, 1H), 5.67 (ddd,J= 29.7, 9.6, 2.6 Hz, 1H), 4.56-3.91 (m, 4H), 2.60-2.45 (m, 1H), 2.38 (s, 3H), 2.32-2.10 (m, 1H), 1.57-1.47 (m, 9H).; 426 [M+H] + 88 1-((2S,4S)-4-((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-2-methylpyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 7.05-6.95 (m, 2H), 6.57-6.32 (m, 4H), 6.07-5.99 (m, 1H), 5.75-5.60 (m, 1H), 4.56-3.81 (m, 4H), 2.60-2.13 (m, 5H), 1.54-1.36 (m, 9H).; 426 [M+H] + 89 (R)-1-(2-(((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl)pyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 7.03-6.94 (m, 2H), 6.73 (dd,J= 16.7, 10.3 Hz, 0.5H), 6.54-6.43 (m, 2.5H), 6.39 (td,J= 16.9, 1.7 Hz, 1H), 5.67 (dd,J= 10.2, 1.8 Hz, 0.5H), 5.61 (dd,J= 10.3, 1.7 Hz, 0.5H), 4.84 (m, 1H), 4.73-4.42 (m, 3H), 3.78-3.58 (m, 2H), 2.38 (s, 1.5H), 2.37 (s, 1.5H), 2.33-1.94 (m, 4H), 1.5.-1.46 (m, 6H).; 426 [M+H] + 90 (R)-1-(2-(((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl)azetidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 7.01-6.94 (m, 2H), 6.69-6.17 (m, 4H), 5.64 (dd,J= 26.0, 10.3 Hz, 1H), 5.07-4.77 (m, 3H), 4.49 (dt,J= 13.4, 6.7 Hz, 1H), 4.19 (ddd,J= 18.5, 14.7, 7.3 Hz, 2H), 2.64-2.42 (m, 2H), 2.39 (d,J= 14.4 Hz, 3H), 1.49 (d,J= 3.9 Hz, 6H).; 412 [M+H] + 91 1-((3R,4R)-3-fluoro-4-((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 7.13-6.96 (m, 2H), 6.56-6.35 (m, 4H), 6.01 (ddd,J= 34.5, 7.8, 4.1 Hz, 1H), 5.73 (ddd,J= 19.2, 8.1, 4.1 Hz, 1H), 5.56-5.32 (m, 1H), 4.49 (m, 1H), 4.19-3.84 (m, 4H), 2.46-2.35 (m, 3H), 1.57-1.43 (m, 6H).; 430 [M+H] + 92 rac-1-((3S,4R)-3-((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-4-methylpyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 9.77 (br s, 1H), 7.03 (dd,J= 6.4, 1.0 Hz, 1H), 6.98 (dd,J= 8.7, 3.2 Hz, 1H), 6.65-6.22 (m, 4H), 5.81-5.47 (m, 2H), 4.48 (m, 1H), 4.28-3.36 (m, 4H), 2.75-2.59 (m, 1H), 2.42-2.32 (m, 3H), 1.55-1.45 (m, 6H), 1.20 (dd,J= 7.1, 3.0 Hz, 3H).; 426 [M+H] + 93 (R)-1-(4,4-difluoro-2-(((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 7.08-6.86 (m, 2H), 6.76-6.25 (m, 4H), 5.73 (dd,J= 29.6, 9.6 Hz, 1H), 5.03-3.83 (m, 6H), 2.80-2.55 (m, 2H), 2.38 (s, 1.5H), 2.35 (s, 1.5H), 1.49 (d,J= 6.6 Hz, 6H).; 462 [M+H] + 94 1-((2R,4S)-2-(((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl)-4-methoxypyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 7.02-6.96 (m, 2H), 6.68 (dd,J= 16.6, 10.3 Hz, 0.5H), 6.50-6.33 (m, 3.5H), 5.68 (d,J= 10.2 Hz, 0.5H), 5.64 (d,J= 10.4 Hz, 0.5H)., 4.92 (m, 0.5H), 4.81 (m, 1H), 4.62 (m, 1.5H), 4.47 (m, 1H), 4.33 (m, 0.5H), 4.18 (m, 0.5H), 4.03 (dd,J= 13.0, 2.9 Hz, 0.5H), 3.91 (dd,J= 10.6, 6.0 Hz, 0.5H), 3.65 (m, 1H), 3.34 (s, 1.5H), 3.33 (s, 1.5H), 2.39 (s, 1.5H), 2.38 (s, 1.5H), 2.34 (m, 2H), 2.15 (m, 1H), 1.50 (s, 3H), 1.49 (s, 3H).; 456 [M+H] + 95 (S)-1-(3-((1-isopropyl-6-((6-(trifluoromethyl)pyrimidin-4-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO-d6) δ 10.47 (s, 1H), 8.84 (s, 1H), 8.22-7.26 (m, 3H), 6.60 (ddd,J= 48.5, 16.7, 10.3 Hz, 1H), 6.45 (s, 1H), 6.15 (ddd,J= 16.7, 5.4, 2.2 Hz, 1H), 5.75-5.60 (m, 2H), 4.67-4.47 (m, 1H), 4.05-3.5 0(m, 4H), 2.39-2.13 (m, 2H), 1.45 (d,J= 6.5 Hz, 6H).; 461 [M+H] +96 1-((2R,4S)-4-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-2-methylpyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 7.01 (d,J= 11.9 Hz, 1H), 6.85 (dd,J= 6.7, 3.0 Hz, 1H), 6.62-6.29 (m, 4H), 5.99 (s, 1H), 5.68 (ddd,J= 29.7, 9.4, 2.5 Hz, 1H), 4.56-4.25 (m, 1H), 4.09-3.70 (m, 4H), 2.60-2.49 (m, 1H), 2.38 (s, 3H), 2.15 (d,J= 11.0 Hz, 2H), 1.52 (d,J= 6.1 Hz, 3H), 0.92 (dd,J= 14.9, 9.8 Hz, 6H).; 440 [M+H] + 97 (S)-1-(3-((1-(cyclopropylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 7.08 (s, 1H), 6.94 (d,J= 9.0 Hz, 1H), 6.67-6.56 (m, 1H), 6.53 (dd,J= 17.9, 9.0 Hz, 1H), 6.42 (dd,J= 6.4, 4.3 Hz, 1H), 5.92 (d,J= 30.7 Hz, 1H), 5.75-5.65 (m, 1H), 4.06-3.99 (m, 2H), 3.96-3.81 (m, 5H), 2.38 (d,J= 3.1 Hz, 3H), 2.24-2.18 (m, 2H), 0.65 (d,J= 7.4 Hz, 2H), 0.37 (d,J= 3.9 Hz, 2H).; 424 [M+H] + 98 1-((2R,4S)-4-((1-(cyclopropylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-2-methylpyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 10.19 (s, 1H), 7.04 (d,J= 7.2 Hz, 1H), 6.97 (dd,J= 10.0, 3.1 Hz, 1H), 6.58-6.35 (m, 4H), 6.02 (dd,J= 9.8, 4.3 Hz, 1H), 5.67 (ddd,J= 30.2, 9.5, 2.5 Hz, 1H), 4.55-4.26 (m, 1H), 4.12 (dt,J= 12.0, 5.5 Hz, 1H), 3.98 (dd,J= 30.9, 13.3 Hz, 1H), 3.88-3.78 (m, 2H), 2.53 (dtt,J= 20.0, 17.0, 8.4 Hz, 1H), 2.39 (s, 3H), 2.31-2.07 (m, 2H), 1.52 (d,J= 6.3 Hz, 3H), 0.64 (t,J= 6.8 Hz, 2H), 0.39-0.32 (m, 2H).; 438 [M+H] + 99 (S)-1-(3-((1-cyclopentyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 10.46 (s, 1H), 7.02 (d,J= 10.3 Hz, 1H), 6.95 (dd,J= 5.5, 3.4 Hz, 1H), 6.55-6.35 (m, 4H), 6.01 (d,J= 21.5 Hz, 1H), 5.68 (ddd,J= 26.6, 9.3, 2.8 Hz, 1H), 4.59 (dd,J= 13.4, 6.8 Hz, 1H), 4.07-3.96 (m, 1H), 3.96-3.72 (m, 3H), 2.52-2.43 (m, 1H), 2.38 (d,J= 5.9 Hz, 3H), 2.33-2.24 (m, 1H), 2.18 (d,J= 6.9 Hz, 2H), 1.83 (d,J= 59.5 Hz, 6H).; 438 [M+H] + 100 1-((2R,4S)-4-((1-cyclopentyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-2-methylpyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 10.64 (s, 1H), 7.05 (d,J= 7.0 Hz, 1H), 6.95 (dd,J= 10.3, 3.0 Hz, 1H), 6.59-6.33 (m, 4H), 6.03 (dd,J= 9.9, 4.9 Hz, 1H), 5.72-5.58 (m, 1H), 4.64-4.54 (m, 1H), 4.53-4.21 (m, 1H), 4.13 (dd,J= 12.6, 5.0 Hz, 1H), 4.07-3.91 (m, 1H), 2.53 (dddd,J= 29.2, 23.6, 14.6, 8.8 Hz, 1H), 2.39 (s, 3H), 2.32-2.13 (m, 3H), 1.84 (d,J= 63.4 Hz, 6H), 1.52 (dd,J= 6.3, 2.3 Hz, 3H).; 452 [M+H] + 101 (S)-1-(3-((1-isopropyl-6-((6-methylpyrimidin-4-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 8.68 (d,J= 5.6 Hz, 1H), 7.45-7.30 (m, 2H), 7.12-7.01 (m, 2H), 6.56-6.35 (m, 3H), 5.80-5.61 (m, 2H), 4.65-4.51 (m, 1H), 4.04-3.72 (m, 4H), 2.44 (d,J= 5.4 Hz, 3H), 2.38-2.16 (m, 2H), 1.52 (d,J= 6.6 Hz, 6H).; 407 [M+H] + 102 (S)-1-(3-((6-((5-methylthiazol-2-yl)amino)-1-((1-(trifluoromethyl)cyclopropyl)methyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 9.47 (s, 1H), 7.03 (t,J= 7.5 Hz, 1H), 6.83 (dd,J= 5.2, 3.3 Hz, 1H), 6.62-6.33 (m, 4H), 6.00 (d,J= 23.0 Hz, 1H), 5.69 (ddd,J= 23.4, 9.4, 2.9 Hz, 1H), 4.39-4.29 (m, 2H), 4.07-4.01 (m, 1H), 3.95-3.74 (m, 3H), 2.50 (d,J= 11.3 Hz, 1H), 2.39 (d,J=3.6 Hz, 3H), 2.29 (ddd,J= 45.3, 25.0, 4.6 Hz, 2H), 1.08-1.01 (m, 2H), 0.65 (s, 2H).; 492 [M+H] + 103 (S)-1-(3-((1-isopropyl-6-((6-methoxypyrimidin-4-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 8.43 (s, 1H), 7.51 (br s, 1H), 7.04 (dd,J= 6.1, 3.2 Hz, 1H), 6.99-6.87 (m, 2H), 6.56-6.37 (m, 3H), 5.81-5.64 (m, 2H), 4.55 (m, 1H), 4.03-3.74 (m, 7H), 2.48-2.19 (m, 2H), 1.51 (d,J= 6.6 Hz, 6H).; 423 [M+H] + 104 (S)-1-(3-((1-isobutyl-6-((6-methylpyrimidin-4-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 8.67 (d,J= 4.7 Hz, 1H), 7.23 (d,J= 11.8 Hz, 1H), 7.08 (d,J= 14.9 Hz, 1H), 6.90 (dd,J= 7.1, 3.0 Hz, 1H), 6.56-6.37 (m, 3H), 5.81-5.63 (m, 2H), 4.04-3.92 (m, 1H), 3.92-3.75 (m, 5H), 2.46 (s, 1H), 2.43 (d,J= 5.1 Hz, 3H), 2.35-2.13 (m, 2H), 0.94 (dd,J= 6.4, 2.6 Hz, 6H).; 421 [M+H] + 105 1-((3S,4R)-3-fluoro-4-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 9.79 (s, 1H), 6.99 (s, 1H), 6.89 (d,J= 2.6 Hz, 1H), 6.62-6.36 (m, 4H), 5.78 (ddd,J= 22.3, 13.1, 12.1 Hz, 1H), 5.58 (d,J= 54.0 Hz, 1H), 4.37 (t,J= 8.0 Hz, 1H), 4.09 (dd,J= 24.4, 15.0 Hz, 1H), 3.93-3.71 (m, 4H), 2.32 (t,J= 17.8 Hz, 3H), 2.18-2.11 (m, 1H), 0.90 (dd,J= 29.2, 6.5 Hz, 6H).444 [M+H] + 106 1-((3R,4R)-3-fluoro-4-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 11.14 (s, 1H), 7.06 (d,J= 5.5 Hz, 1H), 6.84 (dd,J= 5.4, 3.3 Hz, 1H), 6.55-6.31 (m, 4H), 6.02 (ddd,J= 34.3, 7.6, 3.9 Hz, 1H), 5.73 (ddd,J= 19.5, 8.2, 3.9 Hz, 1H), 5.46 (dd,J= 49.9, 35.6 Hz, 1H), 4.01 (dddd,J= 46.9, 28.5, 25.4, 13.7 Hz, 4H), 3.78 (d,J= 7.2 Hz, 2H), 2.49-2.33 (m, 3H), 2.15 (tt,J= 13.8, 6.8 Hz, 1H), 0.98-0.77 (m, 6H).; 444 [M+H] + 107 1-((3R,4S)-3-((1-(cyclopropylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-4-fluoropyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 10.97 (s, 1H), 7.06 (d,J= 6.0 Hz, 1H), 6.97 (dd,J= 6.6, 3.2 Hz, 1H), 6.53-6.37 (m, 4H), 6.01 (ddd,J= 34.5, 7.6, 3.9 Hz, 1H), 5.73 (ddd,J= 19.9, 7.8, 4.4 Hz, 1H), 5.44 (dd,J= 50.1, 33.6 Hz, 1H), 4.24-3.87 (m, 4H), 3.84 (d,J= 6.8 Hz, 2H), 2.41 (d,J=6.0 Hz, 3H), 1.22 (dd,J= 11.7, 5.9 Hz, 1H), 0.64 (t,J= 6.6 Hz, 2H), 0.35 (d,J= 3.6 Hz, 2H).; 442 [M+H] + 108 1-((3R,4R)-3-((1-(cyclopropylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-4-fluoropyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 10.53 (s, 1H), 7.01 (dd,J= 13.1, 9.8 Hz, 2H), 6.60-6.40 (m, 4H), 5.86 (ddd,J= 33.1, 20.1, 15.0 Hz, 1H), 5.80-5.49 (m, 2H), 4.44-4.32 (m, 1H), 4.15-3.75 (m, 5H), 2.36 (d,J= 15.7 Hz, 3H), 1.22 (d,J= 6.9 Hz, 1H), 0.69-0.58 (m, 2H), 0.36 (t,J= 4.9 Hz, 2H).; 442 [M+H] + 109 1-((3R,4S)-3-((1-cyclopentyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-4-fluoropyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 7.08-6.96 (m, 2H), 6.67-6.38 (m, 4H), 5.92-5.47 (m, 3H), 4.63 (t,J= 5.5 Hz, 1H), 4.36 (t,J= 8.6 Hz, 1H), 4.18-3.78 (m, 3H), 2.35 (s, 3H), 2.24-2.13 (m, 2H), 2.00-1.70 (m, 6H).; 456 [M+H] + 110 1-((3R,4R)-3-((1-cyclopentyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-4-fluoropyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 7.07-6.93 (m, 2H), 6.57-6.38 (m, 4H), 6.07-5.93 (m, 1H), 5.74 (ddd,J= 19.0, 7.9, 4.2 Hz, 1H), 5.55-5.34 (m, 1H), 4.64-4.55 (m, 1H), 4.22-3.82 (m, 4H), 2.40 (s, 3H), 2.25-2.12 (m, 2H), 1.97-1.70(m, 6H).; 456 [M+H] + 111 1-((S)-3-((1-((S)-sec-butyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 7.01 (dd,J= 8.9, 0.8 Hz, 1H), 6.95 (dd,J= 5.4, 3.4 Hz, 1H), 6.57-6.35 (m, 4H), 6.00 (m, 1H), 5.68 (ddd,J= 25.1, 9.5, 2.8 Hz, 1H), 4.26-4.16 (m, 1H), 4.08-3.74 (m, 4H), 2.55-2.24 (m, 5H), 1.85 (m, 2H), 1.48 (dd,J= 6.7, 3.5 Hz, 3H), 0.83 (t,J= 7.4 Hz, 3H).; 426 [M+H] + 112 1-((3R,4S)-3-((1-((S)-sec-butyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-4-fluoropyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 7.06-6.94 (m, 2H), 6.67-6.38 (m, 4H), 5.89-5.50 (m, 3H), 4.41-3.79 (m, 5), 2.357-2.32 (m, 3H), 1.90-1.81 (m, 2H), 1.48 (t,J= 3.3 Hz, 3H), 0.83 (t,J= 7.3 Hz, 3H).; 444 [M+H] + 113 1-((3R,4R)-3-((1-((S)-sec-butyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-4-fluoropyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 7.08-6.85 (m, 2H), 6.74-6.31 (m, 4H), 6.20-5.87 (m, 1H), 5.74 (ddd,J= 16.8, 7.7, 4.5 Hz, 1H), 5.59-5.26 (m, 1H), 4.44-3.74 (m, 5H), 2.39 (d,J= 3.9 Hz, 3H), 1.92-1.76 (m, 2H), 1.56-1.41 (m, 3H), 0.82 (t,J= 7.3 Hz, 3H).; 444 [M+H] + 114 (S)-1-(3-((1-isopentyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 11.24 (s, 1H), 7.09 (t,J= 10.4 Hz, 1H), 6.91-6.82 (m, 1H), 6.63-6.38 (m, 4H), 6.14-6.01 (m, 1H), 5.68 (ddd,J= 15.4, 12.2, 7.6 Hz, 1H), 3.93 (dddd,J= 39.9, 29.8, 18.8, 11.6 Hz, 6H), 2.69-2.19 (m, 6H), 1.61 (td,J= 12.7, 6.3 Hz, 1H), 0.99 (t,J= 9.0 Hz, 6H).; 440 [M+H] + 115 1-((3R,4R)-3-fluoro-4-((1-isopentyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 7.09 (d,J= 5.8 Hz, 1H), 6.87 (dd,J= 5.6, 3.1 Hz, 1H), 6.45 (td,J= 16.6, 5.1 Hz, 4H), 6.12-5.97 (m, 1H), 5.73 (ddd,J= 20.3, 8.1, 4.0 Hz, 1H), 5.46 (dd,J= 49.3, 35.0 Hz, 1H), 4.28-3.76 (m, 6H), 2.40 (d,J= 5.1 Hz, 3H), 1.80-1.51 (m, 3H), 0.98 (d,J=6.5 Hz, 6H).; 458 [M+H] + 116 1-(3-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-4-methylpyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 7.00 (d,J= 6.2 Hz, 1H), 6.76 (dd,J= 10.1, 2.8 Hz, 1H), 6.49-6.29 (m, 4H), 5.65-5.55 (m, 2H), 4.20 (m, 1H), 3.95-3.82 (m, 2H), 3.75-3.66 (m, 2H), 3.41 (m, 1H), 2.62 (m, 1H), 2.32 (s, 3H), 2.07 (m, 1H), 1.14 (dd,J= 6.9, 3.8 Hz, 3H), 0.89-0.84 (m, 6H).; 440 [M+H] + 117 (S)-1-(3-((6-((5-methylthiazol-2-yl)amino)-1-(pyridin-2-ylmethyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 8.50 (m, 1H), 7.57 (t,J= 7.7 Hz, 1H), 7.20 (m, 1H), 6.98 (dd,J= 5.9, 3.2 Hz, 1H), 6.88 (s, 1H), 6.74 (dd,J= 17.6, 7.9 Hz, 1H), 6.58-6.35 (m, 4H), 6.01 (d,J= 20.2 Hz, 1H), 5.69 (ddd,J= 25.3, 9.3, 3.0 Hz, 1H), 5.33 (s, 2H), 4.08-3.75 (m, 4H), 2.55-2.26 (m, 5H).; 461 [M+H] + 118 1-(3-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)azetidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 7.05 (s, 1H), 6.86 (d,J= 3.0 Hz, 1H), 6.51 (d,J= 3.0 Hz, 1H), 6.44 (s, 1H), 6.37 (dd,J= 16.9, 1.1 Hz, 1H), 6.23 (dd,J= 17.0, 10.3 Hz, 1H), 5.86 (m, 1H), 5.68 (dd,J= 10.4, 1.1 Hz, 1H), 4.82- 4.61 (m, 2H), 4.30 (ddd,J= 14.8, 10.5, 3.2 Hz, 2H), 3.79 (d,J= 7.3 Hz, 2H), 2.43 (s, 3H), 2.16 (m, 1H), 0.94 (d,J= 6.5 Hz, 7H).412 [M+H] + 119 1-(3-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-3-methylazetidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 6.98 (s, 1H), 6.87 (s, 1H), 6.70 (s, 1H), 6.48 (s, 1H), 6.39-6.18 (m, 2H), 5.67 (d,J= 10.3 Hz, 1H), 4.67-4.30 (m, 4H), 3.81 (d,J= 6.8 Hz, 2H), 2.40 (s, 3H), 2.18 (m, 1H), 2.01 (s, 3H), 0.93 (d,J= 5.7 Hz, 6H).; 426 [M+H] + 120 1-((3R,4R)-3-fluoro-4-((6-((5-methylthiazol-2-yl)amino)-1-((1-(trifluoromethyl)cyclopropyl)methyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 11.52 (s, 1H), 7.11 (d,J= 5.9 Hz, 1H), 6.81 (dd,J= 6.7, 2.8 Hz, 1H), 6.46 (dt,J= 18.2, 8.5 Hz, 4H), 6.09-5.94 (m, 1H), 5.74 (ddd,J= 19.2, 7.6, 4.4 Hz, 1H), 5.45 (dd,J= 49.3, 38.3 Hz, 1H), 4.43-3.76 (m, 7H), 2.41 (d,J= 5.6 Hz, 3H), 1.04 (d,J= 4.7 Hz, 2H), 0.62 (s, 2H).; 510 [M+H] + 121 (S)-1-(3-((1-benzyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 7.35-7.27 (m, 3H), 7.08 (t,J= 7.3 Hz, 2H), 6.92 (dd,J= 6.5, 3.2 Hz, 1H), 6.84 (s, 1H), 6.59-6.35 (m, 4H), 6.00 (d,J= 22.6 Hz, 1H), 5.74-5.61 (m, 1H), 5.21 (s, 2H), 4.11-3.72 (m, 4H), 2.56-2.23 (m, 5H).; 460 [M+H] + 122 (S)-1-(3-((6-((5-ethylthiazol-2-yl)amino)-1-isobutyl-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 7.02-6.84 (m, 2H), 6.57-6.37 (m, 4H), 5.94 (d,J= 29.8 Hz, 1H), 5.69 (ddd,J= 22.5, 9.1, 3.2 Hz, 1H), 4.06-3.70 (m, 6H), 2.80-2.72 (m, 2H), 2.60-2.09 (m, 3H), 1.32 (t,J= 7.5 Hz, 3H), 0.95-0.81 (m, 6H).; 440 [M+H] + 123 1-((3S)-3-((1-(2-methylbutyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 7.06 (d,J= 8.3 Hz, 1H), 6.81 (dd,J= 7.4, 2.8 Hz, 1H), 6.56-6.34 (m, 4H), 6.03 (d,J= 15.4 Hz, 1H), 5.72-5.60 (m, 1H), 4.09-3.65 (m, 6H), 2.57-1.87 (m, 6H), 1.41 (m, 1H), 1.20 (m, 1H), 1.02-0.77 (m, 6H).; 440 [M+H] + 124 (S)-1-(3-((1-butyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 10.39 (s, 1H), 7.04 (d,J= 8.6 Hz, 1H), 6.85 (dd,J= 7.4, 3.1 Hz, 1H), 6.62-6.31 (m, 4H), 6.03 (d,J= 17.2 Hz, 1H), 5.68 (ddd,J= 26.2, 9.6, 2.5 Hz, 1H), 4.15-3.68 (m, 6H), 2.67-2.19 (m, 5H), 1.86-1.69 (m, 2H), 1.38-1.28 (m, 2H), 0.94 (tt,J= 24.1, 12.1 Hz, 3H).; 426 [M+H] + 125 (S)-1-(3-((1-ethyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO-d6) δ 10.61 (s, 1H), 7.16 (t,J= 2.7 Hz, 1H), 6.97 (s, 1H), 6.70-6.51 (m, 2H), 6.35 (s, 1H), 6.14 (ddd,J= 16.7, 6.1, 2.0 Hz, 1H), 5.90 (d,J= 41.9 Hz, 1H), 5.66 (ddd,J= 26.2, 10.3, 2.0 Hz, 1H), 4.11-3.49 (m, 6H), 2.45-2.16 (m, 5H), 1.31 (t,J= 7.2 Hz, 3H).; 398 [M+H] + 126 (S)-1-(3-((6-((5-methylthiazol-2-yl)amino)-1-propyl-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, DMSO-d6) δ 10.57 (s, 1H), 7.14 (t,J= 2.6 Hz, 1H), 6.96 (s, 1H), 6.70-6.50 (m, 2H), 6.34 (d,J= 2.7 Hz, 1H), 6.14 (ddd,J= 16.7, 6.6, 2.1 Hz, 1H), 5.90 (d,J= 42.0 Hz, 1H), 5.66 (ddd,J= 26.8, 10.3, 2.1 Hz, 1H), 4.13-3.48 (m, 6H), 2.45-2.15 (m, 5H), 1.78-1.65 (m, 2H), 0.81 (t,J= 7.3 Hz, 3H).; 412 [M+H] + 127 (S)-1-(3-((1-(2-methoxyethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO-d6) δ 10.60 (s, 1H), 7.13 (t,J= 2.9 Hz, 1H), 6.96 (s, 1H), 6.69-6.50 (m, 2H), 6.35 (s, 1H), 6.14 (ddd,J= 16.7, 6.3, 2.2 Hz, 1H), 5.90 (d,J= 42.0 Hz, 1H), 5.67 (ddd,J= 26.2, 10.3, 2.1 Hz, 1H), 4.15 (t,J= 5.1 Hz, 2H), 4.10-3.48 (m, 4H), 3.62 (t,J= 5.1 Hz, 2H), 3.21 (s, 3H), 2.45-2.15 (m, 5H).; 428 [M+H] + 128 (S)-1-(3-((1-(cyclopentylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 10.93 (s, 4H), 7.09-7.03 (m, 1H), 6.85 (dd,J= 7.9, 3.2 Hz, 1H), 6.57-6.35 (m, 4H), 6.04 (dd,J= 10.0, 7.9 Hz, 1H), 5.67 (ddd,J= 26.2, 9.6, 2.7 Hz, 1H), 4.08-3.75 (m, 7H), 2.51-2.29 (m, 6H), 1.66 (dd,J= 30.8, 28.1 Hz, 7H).; 452 [M+H] + 129 (S)-1-(3-((1-(cyclohexylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 10.14 (s, 1H), 7.04 (d,J= 8.0 Hz, 1H), 6.82 (dd,J= 7.4, 3.1 Hz, 1H), 6.63-6.32 (m, 4H), 6.03 (d,J= 16.7 Hz, 1H), 5.68 (ddd,J= 25.5, 9.6, 2.4 Hz, 1H), 4.13-3.73 (m, 6H), 2.60-2.27 (m, 5H), 1.84-1.57 (m, 6H), 1.08 (ddd,J= 34.7, 30.1, 12.5 Hz, 5H).; 466 [M+H] + 130 (S)-1-(3-((1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 7.26 (s, 1H), 7.01 (d,J= 12.1 Hz, 1H), 6.86-6.78 (m, 1H), 6.58-6.35 (m, 4H), 5.99 (d,J= 25.1 Hz, 1H), 5.76-5.61 (m, 1H), 4.09-3.98 (m, 1H), 3.98- 3.72 (m, 3H), 3.68 (a, 3H), 2.50-2.20 (m, 5H). 384 [M+H] + 131 1-((3S,4R)-3-fluoro-4-((1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO-d6) δ 10.69 (s, 1H), 7.17 (s, 1H), 6.98 (s, 1H), 6.75 (s, 1H), 6.65 (dd,J= 16.5, 10.4 Hz, 1H), 6.40 (s, 1H), 6.22 (d,J= 16.7 Hz, 1H), 5.95-5.53 (m, 3H), 4.53-4.24 (m, 1H), 3.94-3.41 (m, 5H), 2.28 (d,J= 9.9 Hz, 3H). 402 [M+H] + 132 1-((3R,4S)-3-((1-(cyclopentylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-4-fluoropyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 9.68 (s, 1H), 7.02 (s, 1H), 6.91 (d,J= 3.0 Hz, 1H), 6.60 - 6.38 (m, 4H), 5.92 - 5.81 (m, 1H), 5.80 - 5.48 (m, 2H), 4.38 (t,J= 8.7 Hz, 1H), 4.15 - 3.76 (m, 5H), 2.40 (d,J= 7.4 Hz, 1H), 2.36 (d,J= 15.4 Hz, 3H), 1.76 - 1.53 (m, 6H), 1.32 - 1.23 (m, 2H). 470 [M+H] + 133 (S)-1-(3-((6-((5-methylthiazol-2-yl)amino)-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 9.26 (s, 1H), 7.01 (d,J= 8.4 Hz, 1H), 6.86 - 6.78 (m,J= 5.9, 3.1 Hz, 1H), 6.55 - 6.32 (m,J= 21.1, 4H), 6.01 (d,J= 19.6 Hz, 1H), 5.73 - 5.59 (m, 1H), 4.05 (d,J= 14.1 Hz, 1H), 3.96 - 3.87 (m, 2H), 3.82 (t,J= 11.1 Hz, 3H), 2.39 (s, 3H), 1.85 - 1.58 (m, 8H), 1.20 (d,J= 13.2 Hz, 3H). 468 [M+H] + 134 1-((3S,4S)-3-fluoro-4-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 9.42 (s, 1H), 7.03 (d,J= 5.8 Hz, 1H), 6.90 - 6.79 (m, 1H), 6.53 - 6.29 (m, 4H), 6.11 - 5.89 (m, 1H), 5.78 - 5.66 (m, 1H), 5.45 (dd,J= 49.2, 36.9 Hz, 1H), 4.20 - 3.85 (m, 5H), 3.79 (d,J= 7.3 Hz, 1H), 2.40 (d,J= 4.2 Hz, 3H), 2.15 (dt,J= 13.4, 6.7 Hz, 1H), 0.93 (d,J= 6.3 Hz, 6H). 444 [M+H] + 135 1-((3R,4S)-3-fluoro-4-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, DMSO) δ 10.56 (s, 1H), 7.18 (t, J = 3.5 Hz, 1H), 6.95 (s, 1H), 6.76 (d, J = 3.1 Hz, 1H), 6.69 - 6.57 (m, 1H), 6.40 (t, J = 3.4 Hz, 1H), 6.21 (d, J = 16.7 Hz, 1H), 5.89 - 5.54 (m, 3H), 4.49 - 4.22 (m, 1H), 3.87 - 3.66 (m, 5H), 2.26 (d, J = 10.7 Hz, 3H), 2.09 (dt, J = 13.4, 6.7 Hz, 1H), 0.84 (d, J = 6.5 Hz, 6H), 444 [M+H]+136 1-(6-((1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-1-azaspiro[3.3]heptan-1-yl)prop-2-en-1-one 1H NMR (500 MHz, DMSO-d6) δ 10.62 (s, 1H), 7.12 (s, 1H), 6.97 (s, 1H), 6.59 (s, 1H), 6.39 (s, 1H), 6.30-6.05 (m, 2H), 5.80-5.35(m, 2H), 4.16 (s, 2H), 3.65 (s, 3H), 3.15, s, 2H), 2.74 (s, 2H), 2.45 (s, 2H), 2.33 (s, 3H). 410 [M+H] + 137 1-(6-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-1-azaspiro[3.3]heptan-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO-d6) δ 10.51 (s, 1H), 7.14 (d,J= 3.1 Hz, 1H), 6.96 (s, 1H), 6.66-6.56 (m, 1H), 6.44-6.38 (m, 1H), 6.24 (dd,J= 16.9, 10.2 Hz, 1H), 6.11 (dd,J= 16.9, 1.9 Hz, 1H), 4.22-3.78 (m, 4H), 3.15 (td,J= 8.6, 2.4 Hz, 2H), 2.80-2.70 (m, 2H), 2.47-2.41 (m, 2H), 2.33 (s, 3H), 2.12-2.04 (m, 1H), 0.84 (d,J= 6.6 Hz, 6H). 452 [M+H] + 138 (S)-1-(3-((6-((5-fluoro-2-methylphenyl)amino)-1-methyl-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, DMSO-d6) δ 7.76 (d,J= 10.9 Hz, 1H), 7.73-7.57 (m, 1H), 7.13 (t,J= 7.6 Hz, 1H), 7.07 (t,J= 3.0 Hz, 1H), 6.70-6.47 (m, 3H), 6.31 (s, 1H), 6.21-6.10 (m, 1H), 5.67 (dd,J= 20.5, 10.4 Hz, 1H), 5.59 (d,J= 10.4 Hz, 1H), 3.97-3.47 (m, 7H), 2.34-2.11 (m, 5H). 395 [M+H] + 139 1-((3S,4R)-3-fluoro-4-((6-((5-fluoro-2-methylphenyl)amino)-1-methyl-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO-d6) δ 7.82 (d,J= 20.4 Hz, 1H), 7.45 (t,J= 9.9 Hz, 1H), 7.19- 7.08 (m, 2H), 6.70-6.52 (m, 3H), 6.36 (d,J= 6.3 Hz, 1H), 6.18 (d,J= 16.7 Hz, 1H), 5.71 (t,J= 10.3 Hz, 1H), 5.56-5.37 (m, 2H), 4.35-3.52 (m, 7H), 2.22 (s, 3H). 413 [M+H] + 140 (S)-1-(3-((1-(2-hydroxy-2-methylpropyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, MeOD) δ 7.04 (t,J= 3.0 Hz, 1H), 6.90 (s, 1H), 6.73-6.53 (m, 2H), 6.43 (d,J= 3.0 Hz, 1H), 6.28 (ddd,J= 16.8, 9.1, 1.4 Hz, 1H), 6.10-5.98 (m, 1H), 5.74 (ddd,J= 24.7, 10.5, 1.4 Hz, 1H), 4.15-3.64 (m, 6H), 2.50-2.29 (m, 5H, 1.19 (s, 6H). 442 [M+H] + 141 1-((3S,4R)-3-fluoro-4-((1-(2-hydroxy-2-methylpropyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, MeOD) δ 7.08 (t,J= 2.9 Hz, 1H), 6.89 (s, 1H), 6.70-6.58 (m, 2H), 6.49 (t,J= 2.8 Hz, 1H), 6.33 (d,J= 16.8 Hz, 1H), 5.94-5.83 (m, 1H), 5.79 (ddd,J= 15.0, 10.5, 1.7 Hz, 1H), 5.69-5.51 (m, 1H), 4.55-3.58 (m, 6H), 2.30 (d,J= 12.6 Hz, 3H), 1.20 (s, 6H). 460 [M+H] + 142 1-(3-((1-cyclopentyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)azetidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 7.04 - 6.95 (m, 2H), 6.53 (s, 2H), 6.36 (d,J= 17.0 Hz, 1H), 6.24 (d,J= 10.3 Hz, 1H), 5.82 (s, 1H), 5.69 (d,J= 11.2 Hz, 1H), 4.77 - 4.57 (m, 3H), 4.36 - 4.21 (m, 2H), 2.41 (s, 3H), 2.24 - 2.13 (m, 3H), 1.90 (s, 5H). 424 [M+H] + 143 (R)-1-(3-((1-cyclopentyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 7.06 - 6.88 (m, 2H), 6.64 - 6.32 (m, 4H), 5.98 (d,J= 24.5 Hz, 1H), 5.75 - 5.62 (m, 1H), 4.67 - 4.55 (m, 1H), 4.05 - 3.73 (m, 4H), 2.38 (d,J= 1.9 Hz, 3H), 2.24 - 2.14 (m, 2H), 1.83 (d,J= 55.8 Hz, 8H). 438[M+H] + 144 (R)-1-(3-((1-(cyclopropylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy) pyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 7.02 - 6.94 (m, 2H), 6.54 - 6.36 (m, 4H), 5.99 (d,J= 23.5 Hz, 1H), 5.74 - 5.59 (m, 1H), 4.04 (d,J= 15.5 Hz, 1H), 3.95 - 3.78 (m, 5H), 2.52 - 2.45 (m, 1H), 2.38 (d,J= 2.6 Hz, 3H), 0.87 (dd,J= 12.9, 6.0 Hz, 2H), 0.64 (dd,J= 8.2, 2.6 Hz, 2H), 0.38 - 0.33 (m, 2H).424[M+H] + 145 1-(3-((1-(cyclopropylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)azetidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 7.06 - 6.97 (m, 2H), 6.58 - 6.46 (m, 2H), 6.41 - 6.18 (m, 2H), 5.88 - 5.75 (m, 1H), 5.69 (d,J= 10.4 Hz, 1H), 4.79 - 4.59 (m, 2H), 4.37 - 4.21 (m, 2H), 3.87 (d,J= 6.8 Hz, 2H), 2.42 (s, 3H), 0.84 (s, 1H), 0.66 - 0.62 (m, 2H), 0.36 (q,J= 5.0 Hz, 2H).410[M+H] + 146 1-(3-((1-(2-methoxyethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)azetidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, DMSO-d6) δ 10.57 (s, 1H), 7.18 (d,J= 3.2 Hz, 1H), 6.96 (s, 1H), 6.73 (s, 1H), 6.44 (d,J= 3.1 Hz, 1H), 6.36 (dd,J= 17.0, 10.3 Hz, 1H), 6.13 (dd,J= 17.0, 2.0 Hz, 1H), 5.77-5.72 (m, 1H), 5.68 (dd,J= 10.3, 2.0 Hz, 1H), 4.79 (dd,J= 9.5, 6.7 Hz, 1H), 4.51 (dd,J= 11.0, 6.6 Hz, 1H), 4.25 (dd,J= 9.9, 2.8 Hz, 1H), 4.16 (t,J= 5.2 Hz, 2H), 3.97 (dd,J= 11.1, 3.0 Hz, 1H), 3.63 (t,J= 5.2 Hz, 2H), 3.22 (s, 3H), 2.34 (s, 3H). 414[M+H] + 147 1-((3S,4R)-3-fluoro-4-((1-(2-methoxyethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO-d6) δ 10.65 (s, 1H), 7.19 (t,J= 3.5 Hz, 1H), 6.96 (s, 1H), 6.78 (s, 1H), 6.64 (ddd,J= 16.4, 10.3, 3.2 Hz, 1H), 6.40 (t,J= 3.6 Hz, 1H), 6.21 (d,J= 16.7 Hz, 1H), 5.89-5.53 (m, 3H), 4.52-3.42 (m, 8H), 3.21 (s, 3H), 2.27 (d,J= 9.8 Hz, 3H). 446[M+H] + 148 (S)-1-(3-((1-(2-methoxyethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)piperidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, DMSO-d6) δ 10.60 (s, 1H), 7.11 (s, 1H), 6.95 (s, 1H), 6.91- 6.54 (m, 2H), 6.28 (d,J= 26.6 Hz, 1H), 6.04 (dd,J= 38.4, 16.6 Hz, 1H), 5.56 (dd,J= 112.4, 9.6 Hz, 2H), 4.14 (s, 2H), 3.98-3.40 (m, 6H), 3.21 (s, 3H), 2.34-1.48 (m, 7H). 442[M+H] + 149 (S)-1-(3-((1-(cyclopropylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy) piperidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO) δ 10.55 (s, 2H), 7.18 (s, 2H), 6.98 - 6.48 (m, 6H), 6.32 - 5.92 (m, 4H), 5.75 - 5.33 (m, 4H), 4.13 (d,J= 13.1 Hz, 3H), 3.88 (t,J= 11.0 Hz, 13H), 2.26 (d,J= 10.3 Hz, 7H), 2.15 - 1.47 (m, 10H), 1.20 (d,J= 41.0 Hz, 5H), 0.52 (s, 5H), 0.37 (s, 5H).438[M+H] + 150 (S)-1-(3-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)piperidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, DMSO) δ 10.50 (s, 1H), 7.10 (s, 1H), 6.99 - 6.79 (m, 1H), 6.62 - 6.49 (m, 1H), 6.28 (d,J= 28.0 Hz, 1H), 6.02 (dd,J= 49.8, 16.9 Hz, 1H), 5.55 (dd,J= 128.8, 10.5 Hz, 2H), 4.20 - 3.45 (m, 6H), 2.26 (d,J= 10.3 Hz, 3H), 1.86 (dd,J= 187.0, 85.0 Hz, 5H), 0.84 (s, 6H).440[M+H] + 151 (S)-1-(3-((1-cyclopentyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)piperidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO) δ 10.56 (s, 1H), 7.19 (d,J= 3.2 Hz, 1H), 6.95 (s, 1H), 6.69 - 6.48 (m, 2H), 6.35 - 6.18 (m, 1H), 6.14 - 5.93 (m, 1H), 5.73 - 5.35 (m, 2H), 4.65 - 4.56 (m, 1H), 4.16 - 3.53 (m, 5H), 2.26 (d,J= 10.5 Hz, 3H), 2.10 (d,J= 5.7 Hz, 3H), 1.76 (d,J= 70.2 Hz, 9H). 452[M+H] + 152 1-((3R,4S)-3-((1-ethyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-4-fluoropyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 7.02 (s, 1H), 6.90 (t,J= 3.9 Hz, 1H), 6.54 (d,J= 2.7 Hz, 1H), 6.51 - 6.40 (m, 3H), 5.92 - 5.80 (m, 1H), 5.79 - 5.70 (m,J= 12.1, 8.6, 3.5 Hz, 1H), 5.60 (dd,J= 53.8, 16.7 Hz, 1H), 4.37 (t,J= 8.5 Hz, 1H), 4.14 - 3.99 (m, 3H), 3.92 - 3.77 (m, 2H), 2.34 (d,J= 15.4 Hz, 3H), 1.43 (t,J= 7.2 Hz, 3H).;416[M+H] + 153 (S)-1-(3-((1-ethyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)piperidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 7.15 - 6.96 (m, 1H), 6.93 - 6.81 (m, 1H), 6.51 - 6.36 (m, 2H), 6.31 - 6.09 (m, 1H), 5.75 - 5.47 (m, 1H), 5.41 (dd,J= 21.3, 10.5 Hz, 1H), 4.02 (q,J= 6.7 Hz, 2H), 3.90 - 3.80 (m, 2H), 3.69 - 3.55 (m, 1H), 2.30 (d,J= 12.8 Hz, 3H), 2.21 - 2.11 (m, 1H), 2.04 - 1.87 (m, 1H), 1.73 - 1.57 (m, 1H), 1.42 (t,J= 7.1 Hz, 3H).; 412[M+H] + 154 1-((3R,4R)-3-((1-ethyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-4-fluoropyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 7.02 (d,J= 6.1 Hz, 1H), 6.92 - 6.83 (m, 1H), 6.54 - 6.37 (m, 4H), 6.09 - 5.93 (m, 1H), 5.73 (ddd,J= 19.9, 8.1, 3.8 Hz, 1H), 5.44 (dd,J= 49.3, 33.7 Hz, 1H), 4.12 - 3.85 (m, 6H), 2.38 (d,J= 5.2 Hz, 3H), 1.43 (t,J= 6.7 Hz, 3H).; 416[M+H] + 155 1-(3-((1-ethyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-3-methylazetidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 7.03 - 6.90 (m, 2H), 6.82 (s, 1H), 6.51 (s, 1H), 6.35 (d,J= 16.8 Hz, 1H), 6.22 (dd,J= 16.9, 10.2 Hz, 1H), 5.68 (d,J= 10.4 Hz, 1H), 4.61 (d,J= 9.5 Hz, 1H), 4.45 (dd,J= 21.8, 10.3 Hz, 2H), 4.33 (d,J= 11.0 Hz, 1H), 4.09 (q,J= 7.2 Hz, 2H), 2.39 (s, 3H), 1.99 (s, 3H), 1.47 - 1.41 (m, 3H).; 398[M+H] + 156 (R)-1-(3-((1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, DMSO-d6) δ 10.85 (s, 1H), 7.11 (dd,J= 2.9, 1.7 Hz, 1H), 7.00 (s, 1H), 6.70-6.51 (m, 2H), 6.35 (d,J= 3.1 Hz, 1H), 6.14 (ddd,J= 16.7, 6.5, 2.3 Hz, 1H), 5.97-5.83 (m, 1H), 5.66 (ddd,J= 26.9, 10.3, 2.3 Hz, 1H), 4.13-3.44 (m, 7H), 2.45-2.17 (m, 5H). 384[M+H] + 157 1-((3R,4R)-3-fluoro-4-((1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO-d6) δ 11.06 (s, 1H), 7.15 (d,J= 3.2 Hz, 1H), 7.04 (s, 1H), 6.71 (s, 1H), 6.63 (ddd,J= 16.7, 12.9, 10.4 Hz, 1H), 6.36 (d,J= 3.1 Hz, 1H), 6.25-6.15 (m, 1H), 5.90 (ddd,J= 52.8, 8.4, 3.9 Hz, 1H), 5.78-5.68 (m, 1H), 5.51 (dd,J= 48.9, 39.7 Hz, 1H), 4.28-3.69 (m, 7H), 2.31 (s, 3H). 402[M+H] + 158 (S)-1-(3-((1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)piperidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, DMSO-d6)δ 10.80 (s, 1H), 7.09 (s, 1H), 6.98 (s, 1H), 6.90-6.51 (m, 2H), 6.35-6.22 (m, 1H), 6.03 (dd,J= 37.5, 16.6 Hz, 1H), 5.72-5.36 (m, 2H), 4.21-3.35 (m, 7H), 2.36-1.45 (m, 7H). 398[M+H] + 159 1-((3S,4R)-3-fluoro-4-((6-((5-methylthiazol-2-yl)amino)-1-propyl-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO) δ 10.60 (d,J= 11.3 Hz, 1H), 7.28 - 7.18 (m, 1H), 6.96 (s, 1H), 6.77 (s, 1H), 6.69 - 6.58 (m, 1H), 6.49 - 6.37 (m, 1H), 6.21 (d,J= 16.8 Hz, 1H), 5.89 - 5.54 (m, 3H), 4.50 - 4.25 (m, 1H), 4.00 (q,J= 6.9 Hz, 2H), 3.85 - 3.64 (m, 3H), 2.27 (d,J= 10.0 Hz, 2H), 1.75 (q,J= 7.1 Hz, 2H), 0.82 (t,J= 7.3 Hz, 3H).; 430[M+H] + 160 (S)-1-(3-((6-((5-methylthiazol-2-yl)amino)-1-propyl-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)piperidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 7.01 (s, 1H), 6.87 - 6.78 (m, 1H), 6.50 - 6.34 (m, 3H), 6.15 (d,J= 16.5 Hz, 1H), 5.53 (s, 1H), 5.45 - 5.34 (m, 1H), 3.94 (dd,J= 13.2, 6.5 Hz, 2H), 3.85 (dd,J= 16.0, 4.5 Hz, 2H), 3.65 - 3.54 (m, 1H), 2.32 (d,J= 16.0 Hz, 3H), 2.20 - 2.11 (m, 1H), 2.01 - 1.93 (m, 1H), 1.81 (td,J= 14.3, 7.1 Hz, 2H), 1.71 - 1.58 (m, 1H), 0.92 (t,J= 7.3 Hz, 2H).; 426[M+H] + 161 1-((3R,4R)-3-fluoro-4-((6-((5-methylthiazol-2-yl)amino)-1-propyl-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO) δ 10.63 (s, 1H), 7.18 (d,J= 2.6 Hz, 1H), 6.98 (s, 1H), 6.71 (s, 1H), 6.68 - 6.57 (m, 1H), 6.36 (d,J= 2.7 Hz, 1H), 6.19 (d,J= 15.5 Hz, 1H), 5.92 (d,J= 55.3 Hz, 1H), 5.72 (dd,J= 16.6, 11.7 Hz, 1H), 5.52 (dd,J= 48.0, 39.9 Hz, 1H), 4.23 - 3.63 (m, 6H), 2.30 (s, 3H), 1.73 (dd,J= 14.2, 7.1 Hz, 2H), 0.81 (t,J= 7.3 Hz, 3H).; 430[M+H] + 162 (R)-1-(3-((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 9.75 (s, 1H), 7.05-6.95 (m, 2H), 6.58-6.35 (m, 4H), 5.99 (d,J= 23.1 Hz, 1H), 5.68 (ddd,J= 24.9, 9.4, 2.8 Hz, 1H), 4.50 (sep,J= 6.5 Hz, 1H), 4.07-3.74 (m, 4H), 3.70 (s, 3H), 2.56-2.22 (m, 5H), 1.50 (d,J= 6.5 Hz, 6H). 412[M+H] + 163 1-(3-((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-3-methylazetidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 8.78 (s, 1H), 7.00 (d,J= 3.0 Hz, 2H), 6.79 (d,J= 11.0 Hz, 1H), 6.49 (d,J= 3.2 Hz, 1H), 6.34 (dd,J= 16.9, 1.3 Hz, 1H), 6.22 (dd,J= 17.0, 10.3 Hz, 1H), 5.66 (d,J= 10.3 Hz, 1H), 4.61 (d,J= 9.5 Hz, 1H), 4.56-4.42 (m, 3H), 4.31 (d,J= 10.8 Hz, 1H), 2.40 (d,J= 0.8 Hz, 3H), 1.99 (s, 3H), 1.51 (d,J= 6.7 Hz, 6H). 412[M+H] + 164 1-((2S,4S)-4-((1-cyclopentyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-2-methylpyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, DMSO) δ 10.60 (s, 1H), 7.21 (s, 1H), 6.97 (s, 1H), 6.73 - 6.48 (m, 2H), 6.32 (s, 1H), 6.20 - 6.06 (m, 1H), 5.97 - 5.84 (m, 1H), 5.75 - 5.55 (m, 1H), 4.67 - 4.57 (m, 1H), 4.45 - 4.10 (m, 2H), 3.90 - 3.74 (m, 2H), 2.44 - 2.35 (m, 1H), 2.30 (s, 3H), 2.20 - 2.05 (m, 3H), 1.76 (d,J= 69.9 Hz, 5H), 1.31 (t,J= 5.6 Hz, 3H).452[M+H] + 165 1-(3-((1-cyclopentyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-3-methylazetidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO) δ 10.33 (s, 1H), 7.27 - 7.11 (m, 2H), 6.96 (s, 1H), 6.44 - 6.30 (m, 2H), 6.11 (dd,J= 17.0, 1.9 Hz, 1H), 5.67 (dd,J= 10.4, 1.9 Hz, 1H), 4.66 - 4.59 (m, 1H), 4.55 - 4.47 (m, 2H), 4.30 - 4.15 (m, 2H), 2.33 (s, 3H), 2.11 (d,J= 6.3 Hz, 3H), 1.91 (s, 3H), 1.84 (s, 5H)..438[M+H] + 166 1-(3-methyl-3-((1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)azetidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, DMSO-d6) δ 10.37 (s, 1H), 7.13 (d,J= 3.2 Hz, 1H), 7.09 (s, 1H), 6.97 (d,J= 1.2 Hz, 1H), 6.37 (d,J= 3.3 Hz, 1H), 6.36-6.30 (m, 1H), 6.11 (dd,J= 17.0, 2.0 Hz, 1H), 5.67 (dd,J= 10.4, 2.0 Hz, 1H), 4.51 (q,J= 9.8 Hz, 2H), 4.23 (dd,J= 38.2, 11.0 Hz, 2H), 3.66 (s, 3H), 2.33 (s, 3H), 1.91 (s, 3H). 384[M+H] + 167 1-(3-((1-(cyclopropylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-3-methylazetidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO-d6) δ 10.34 (s, 1H), 7.22 (d,J= 3.2 Hz, 1H), 7.14 (s, 1H), 6.97 (s, 1H), 6.38 (d,J= 3.1 Hz, 1H), 6.34 (dd,J= 17.0, 10.4 Hz, 1H), 6.11 (dd,J= 17.0, 1.9 Hz, 1H), 5.67 (dd,J= 10.4, 1.9 Hz, 1H), 4.52 (q,J= 9.9 Hz, 2H), 4.23 (dd,J= 36.4, 11.0 Hz, 2H), 3.88 (d,J= 6.9 Hz, 2H), 2.33 (s, 3H), 1.92 (s, 3H), 1.20-1.13 (m, 1H), 0.56-0.49 (m, 2H), 0.38 (q,J= 4.8 Hz, 2H). 424[M+H] + 168 1-(3-((1-(2-methoxyethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-3-methylazetidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, DMSO-d6) δ 12.22 (s, 1H), 7.51 (d,J= 3.2 Hz, 1H), 7.18-6.92 (m, 2H), 6.69 (d,J= 3.2 Hz, 1H), 6.19 (dd,J= 17.1, 10.1 Hz, 1H), 6.06 (dd,J= 17.1, 2.0 Hz, 1H), 5.59 (dd,J= 10.1, 2.0 Hz, 1H), 4.58-4.30 (m, 4H), 3.87-3.64 (m, 4H), 3.23 (s, 3H), 2.27 (s, 3H), 1.68 (s, 3H). 428[M+H] + 169 (S)-1-(3-((1-(cyclopentylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy) piperidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 7.05 (s, 1H), 6.81 (s, 1H), 6.42 (s, 3H), 6.14 (d,J= 16.7 Hz, 1H), 5.54 (s, 1H), 5.41 (d,J= 10.2 Hz, 1H), 3.95 - 3.51 (m, 6H), 2.37 (s, 4H), 2.20 - 1.83 (m, 3H), 1.61 (d,J= 54.5 Hz, 7H), 1.29 - 1.23 (m, 2H).; 466[M+H] + 170 1-((3R,4R)-3-((1-(cyclopentylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-4-fluoropyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 7.06 (d,J= 5.8 Hz, 1H), 6.86 (dd,J= 5.6, 3.1 Hz, 1H), 6.55 - 6.35 (m, 4H), 6.09 - 5.93 (m, 1H), 5.72 (ddd,J= 19.7, 8.0, 4.1 Hz, 1H), 5.45 (dd,J= 49.4, 33.7 Hz, 1H), 4.21 - 3.82 (m, 6H), 2.38 (dd,J= 19.2, 6.3 Hz, 4H), 1.77 - 1.47 (m, 6H), 1.32 - 1.18 (m, 2H).; 470[M+H] + 171 1-((3S,4R)-3-fluoro-4-((1-(2-methylbutyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 7.05 (s, 1H), 6.86 (d,J= 2.9 Hz, 1H), 6.59 - 6.39 (m, 4H), 5.88 (dt,J= 14.9, 8.5 Hz, 1H), 5.82 - 5.71 (m, 1H), 5.62 (dd,J= 53.8, 17.8 Hz, 1H), 4.37 (dd,J= 18.0, 9.0 Hz, 1H), 4.15 - 3.79 (m, 4H), 3.73 (dd,J= 14.0, 8.0 Hz, 1H), 2.46 - 2.26 (m, 3H), 1.94 (d,J= 6.0 Hz, 1H), 1.41 (dd,J= 12.6, 5.8 Hz, 1H), 1.27 - 1.13 (m, 1H), 1.00 - 0.91 (m, 3H), 0.86 (t,J= 18.1 Hz, 3H).; 458[M+H] + 172 1-((3S)-3-((1-(2-methylbutyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)piperidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 7.06 (s, 1H), 6.78 (s, 1H), 6.48 - 6.33 (m, 3H), 6.14 (d,J= 16.7 Hz, 1H), 5.55 (s, 1H), 5.40 (d,J= 10.6 Hz, 1H), 3.93 - 3.78 (m, 3H), 3.69 (dd,J= 14.1, 7.9 Hz, 1H), 3.64 - 3.51 (m, 1H), 2.36 (s, 3H), 2.22 - 2.13 (m, 1H), 2.12 - 2.05 (m, 1H), 1.96 - 1.87 (m, 1H), 1.71 - 1.61 (m, 1H), 1.46 - 1.34 (m, 1H), 1.21 - 1.11 (m, 1H), 0.92 (t,J= 7.4 Hz, 3H), 0.85 (d,J= 6.6 Hz, 3H).; 454[M+H] + 173 1-((3R,4R)-3-fluoro-4-((1-(2-methylbutyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 6.87 (dd,J= 10.8, 3.8 Hz, 2H), 6.60 (s, 1H), 6.50 - 6.32 (m, 3H), 5.78 (dd,J= 28.9, 22.3 Hz, 1H), 5.74 - 5.66 (m, 1H), 5.38 (dd,J= 49.3, 37.4 Hz, 1H), 4.13 - 3.67 (m, 6H), 2.30 (d,J= 6.1 Hz, 3H), 1.86 (dd,J= 12.4, 6.3 Hz, 1H), 1.40 - 1.25 (m, 1H), 1.17 - 1.06 (m, 1H), 0.89 (t,J= 7.3 Hz, 3H), 0.81 (d,J= 6.3 Hz, 3H).; 458[M+H] + 174 1-((3R,4R)-3-fluoro-4-((1-((R)-2-methylbutyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO) δ 10.60 (s, 1H), 7.15 (d,J= 3.2 Hz, 1H), 6.97 (s, 1H), 6.72 (s, 1H), 6.69 - 6.57 (m, 1H), 6.36 (d,J= 3.1 Hz, 1H), 6.19 (ddd,J= 16.8, 4.2, 2.3 Hz, 1H), 5.91 (ddd,J= 55.0, 8.9, 3.8 Hz, 1H), 5.73 (ddd,J= 16.8, 10.3, 2.2 Hz, 1H), 5.52 (dd,J= 49.1, 41.5 Hz, 1H), 4.20 - 3.67 (m, 6H), 2.34 - 2.26 (m, 3H), 1.92 - 1.82 (m, 1H), 1.35 - 1.06 (m, 2H), 0.89 (t,J= 7.4 Hz, 3H), 0.79 (d,J= 6.6 Hz, 3H).; 458[M+H] + 175 1-((3R,4R)-3-fluoro-4-((1-((S)-2-methylbutyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, DMSO) δ 10.59 (s, 1H), 7.15 (d,J= 3.1 Hz, 1H), 6.97 (s, 1H), 6.72 (s, 1H), 6.63 (ddd,J= 16.7, 12.8, 10.4 Hz, 1H), 6.36 (d,J= 3.0 Hz, 1H), 6.19 (ddd,J= 16.7, 4.0, 2.3 Hz, 1H), 5.91 (ddd,J= 54.9, 8.7, 3.9 Hz, 1H), 5.72 (ddd,J= 17.0, 10.3, 2.0 Hz, 1H), 5.51 (dd,J= 49.4, 39.7 Hz, 1H), 4.21 - 3.67 (m, 6H), 1.86 (dq,J= 13.4, 6.8 Hz, 1H), 1.35 - 1.25 (m, 1H), 1.18 - 1.05 (m, 1H), 0.88 (t,J= 7.4 Hz, 3H), 0.79 (d,J= 6.7 Hz, 3H).; 458[M+H] + 176 1-(3-methyl-3-((6-((5-methylthiazol-2-yl)amino)-1-propyl-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)azetidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO-d6) δ 10.32 (s, 1H), 7.17 (d,J= 3.2 Hz, 1H), 7.08 (s, 1H), 6.97 (d,J= 1.1 Hz, 1H), 6.38 (d,J= 3.1 Hz, 1H), 6.34 (dd,J= 17.0, 10.4 Hz, 1H), 6.11 (dd,J= 17.0, 2.0 Hz, 1H), 5.67 (dd,J= 10.4, 2.0 Hz, 1H), 4.52 (q,J= 9.8 Hz, 2H), 4.23 (dd,J= 37.4, 11.0 Hz, 2H), 3.98 (t,J= 6.9 Hz, 2H), 2.33 (s, 3H), 1.92 (s, 3H), 1.81-1.68 (m, 2H), 0.82 (t,J= 7.4 Hz, 3H). 412[M+H] + 177 1-(3-((1-isopentyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-3-methylazetidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO-d6) δ 10.35 (s, 1H), 7.18 (d,J= 3.2 Hz, 1H), 7.10 (s, 1H), 6.96 (d,J= 1.2 Hz, 1H), 6.40-6.30 (m, 2H), 6.11 (dd,J= 17.0, 2.0 Hz, 1H), 5.67 (dd,J= 10.4, 2.0 Hz, 1H), 4.52 (q,J= 9.8 Hz, 2H), 4.23 (dd,J= 38.4, 11.0 Hz, 2H), 4.03 (t,J= 7.2 Hz, 2H), 2.33 (s, 3H), 1.92 (s, 3H), 1.61 (dd,J= 14.2, 7.0 Hz, 2H), 1.47 (tt,J= 13.3, 6.6 Hz, 1H), 0.92 (d,J= 6.6 Hz, 6H). 440[M+H] + 178 1-(3-((1-(cyclopentylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-3-methylazetidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO-d6) δ 10.31 (s, 1H), 7.18 (d,J= 3.2 Hz, 1H), 7.08 (s, 1H), 6.96 (d,J= 1.0 Hz, 1H), 6.41-6.30 (m, 2H), 6.11 (dd,J= 17.0, 1.9 Hz, 1H), 5.67 (dd,J= 10.4, 2.0 Hz, 1H), 4.52 (q,J= 9.8 Hz, 2H), 4.23 (dd,J= 38.2, 11.0 Hz, 2H), 3.92 (d,J= 7.5 Hz, 2H), 2.40-2.29 (m, 4H), 1.92 (s, 3H), 1.69-1.45 (m, 6H), 1.30-1.19 (m, 2H). 452[M+H] + 179 1-((2S,4S)-4-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-2-methylpyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 7.05 (d,J= 8.0 Hz, 1H), 6.84 - 6.78 (m,J= 5.9, 3.0 Hz, 1H), 6.47 - 6.32 (m, 4H), 6.10 - 6.01 (m, 1H), 5.74 - 5.59 (m, 1H), 4.56 - 4.32 (m, 1H), 4.18 - 4.06 (m, 1H), 3.90 - 3.74 (m, 3H), 2.50 - 2.43 (m, 1H), 2.39 (d, 3H), 2.21 - 2.12 (m, 2H), 1.46 - 1.39 (m, 3H), 0.93 (d,J= 6.4 Hz, 6H).440[M+H] + 180 1-((2S,4S)-4-((1-(cyclopropylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-2-methylpyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 7.08 - 6.99 (m,1H), 6.89 (d,J= 14.5 Hz, 1H), 6.67 - 6.32 (m, 4H), 5.85 (d,J= 24.9 Hz, 1H), 5.75 - 5.58 (m, 1H), 4.55 - 4.30 (m, 1H), 4.18 - 4.02 (m, 1H), 3.97 - 3.77 (m, 3H), 2.58 - 2.38 (m, 1H), 2.31 (d,J= 10.8 Hz, 3H), 2.26 - 2.06 (m, 1H), 1.46 - 1.32 (m, 3H), 1.21 - 1.07 (m, 1H), 0.67 - 0.54 (m, 2H), 0.41 - 0.27 (m, 2H).438[M+H] + 181 2-((4-(((3R,4S)-1-Acryloyl-4-fluoropyrrolidin-3-yl)oxy)-1-isobutyl-1H-pyrrolo[3,2-c]pyridin-6-yl)amino)thiazole-5-carbonitrile 1 H NMR (500 MHz, DMSO) δ 8.18 (s, 1H), 7.30 (s, 1H), 6.81 (s, 1H), 6.65 (dd,J= 16.1, 10.7 Hz, 1H), 6.48 (s, 1H), 6.21 (d,J= 16.4 Hz, 1H), 5.90 (s, 1H), 5.78 - 5.69 (m, 1H), 5.69 - 5.51 (m, 2H), 4.29 (d,J= 92.1 Hz, 1H), 4.16 - 3.99 (m, 1H), 3.94 - 3.71 (m, 4H), 2.14 - 2.05 (m, 1H), 0.85 (d,J= 5.4 Hz, 6H).; 455[M+H] + 182 2-((4-(((3R,4S)-1-Acryloyl-4-fluoropyrrolidin-3-yl)oxy)-1-isobutyl-1H-pyrrolo[3,2-c]pyridin-6-yl)amino)-N-methylthiazole-5-carboxamide 1 H NMR (500 MHz, DMSO) δ 11.19 (s, 1H), 8.20 (d,J= 4.4 Hz, 1H), 7.88 (s, 1H), 7.25 (s, 1H), 6.79 (s, 1H), 6.73 - 6.58 (m, 1H), 6.46 (dd,J= 8.2, 2.5 Hz, 1H), 6.22 (dd,J= 16.0, 5.0 Hz, 1H), 6.01 - 5.82 (m, 1H), 5.81 - 5.60 (m, 2H), 4.42 - 4.17 (m, 1H), 4.14 - 4.01 (m, 1H), 3.93 - 3.73 (m, 3H), 3.56 - 3.48 (m, 1H), 2.73 (d,J= 3.8 Hz, 2H), 2.16 - 2.04 (m, 1H), 0.85 (d,J= 6.4 Hz, 6H).; 487[M+H] + 183 (S)-1-(3-((1-isopropyl-6-((4-methoxypyrimidin-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 8.19 (d,J= 5.7 Hz, 1H), 8.00 (s, 1H), 7.04-6.97 (m, 1H), 6.52-6.32(m, 3H), 6.24 (t,J= 6.2 Hz, 1H), 5.79-5.63 (m, 2H), 4.59 (sep,J= 6.6 Hz, 1H), 4.04 (s, 3H), 3.99-3.73 (m, 4H), 2.45-2.20 (m, 2H), 1.52 (d,J= 6.6 Hz, 6H). 423[M+H] + 184 (S)-1-(3-((1-isopropyl-6-((3-methoxypyrazin-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 8.17 (d,J= 6.9 Hz, 1H), 7.78 (dd,J= 5.2, 3.1 Hz, 1H), 7.64 (d,J= 12.2 Hz, 1H), 7.50 (dd,J= 5.1, 3.1 Hz, 1H), 7.02 (dd,J= 5.7, 3.3 Hz, 1H), 6.56-6.37 (m, 3H), 5.89-5.75 (m, 1H), 5.68 (ddd,J= 19.8, 9.3, 2.9 Hz, 1H), 4.67 (sep,J= 6.6 Hz, 1H), 4.09 (s, 3H), 4.01-3.74 (m, 4H), 2.46-2.15 (m, 2H), 1.53 (d,J= 6.6 Hz, 6H). 436[M+H] + 185 1-((2S,4S)-2-methyl-4-((1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, DMSO-d6) δ 10.69 (s, 1H), 7.10 (d,J= 1.0 Hz, 1H), 6.98 (s, 1H), 6.72-6.47 (m, 2H), 6.30 (s, 1H), 6.14 (dd,J= 24.7, 16.3 Hz, 1H), 5.92 (dd,J= 10.4, 4.6 Hz, 1H), 5.65 (dd,J= 40.9, 9.7 Hz, 1H), 4.44-3.75 (m, 3H), 3.35 (s, 3H), 2.45-2.12 (m, 5H), 1.30 (t,J= 6.7 Hz, 3H). 398[M+H] + 186 1-((2S,4S)-4-((1-ethyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-2-methylpyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO-d6) δ 10.63 (s, 1H), 7.16 (s, 1H), 6.97 (s, 1H), 6.75-6.49 (m, 2H), 6.31 (s, 1H), 6.14 (dd,J= 24.0, 16.7 Hz, 1H), 5.97-5.85 (m, 1H), 5.66 (dd,J= 40.5, 10.3 Hz, 1H), 4.47-3.75 (m, 5H), 2.44-2.13 (m, 5H), 1.35-1.18 (m, 6H). 412[M+H] + 187 1-((2S,4S)-2-methyl-4-((6-((5-methylthiazol-2-yl)amino)-1-propyl-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, DMSO-d6) δ 10.65 (s, 1H), 7.15 (s, 1H), 6.98 (s, 1H), 6.77-6.48 (m, 2H), 6.31 (s, 1H), 6.14 (dd,J= 24.6, 16.7 Hz, 1H), 5.99-5.87 (m, 1H), 5.66 (dd,J= 41.2, 10.2 Hz, 1H), 4.48-3.74 (m, 5H), 2.45-2.12 (m, 5H), 1.73 (dd,J= 13.3, 6.6 Hz, 2H), 1.31 (t,J= 5.1 Hz, 3H), 0.81 (t,J= 6.8 Hz, 3H). 426[M+H] + 188 (S)-1-(3-((1-(2-fluoroethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO-d6) δ 10.65 (s, 1H), 7.16 (s, 1H), 6.97 (s, 1H), 6.71-6.50 (m, 2H), 6.40 (s, 1H), 6.15 (dd,J= 16.7, 6.5 Hz, 1H), 5.91 (d,J= 42.3 Hz, 1H), 5.67 (dd,J= 26.5, 10.3 Hz, 1H), 4.71 (d,J= 47.3 Hz, 2H), 4.33 (d,J= 28.0 Hz, 2H), 4.13-3.48 (m, 4H), 2.46-2.16 (m, 5H). 416[M+H] + 189 1-((3S,4R)-3-fluoro-4-((1-(2-fluoroethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, DMSO-d6) δ 10.68 (s, 1H), 7.22 (t,J= 3.7 Hz, 1H), 6.97 (s, 1H), 6.78 (s, 1H), 6.64 (ddd,J= 16.5, 10.3, 4.1 Hz, 1H), 6.45 (t,J= 3.7 Hz, 1H), 6.21 (dd,J= 16.7, 1.8 Hz, 1H), 5.90-5.54 (m, 3H), 4.73 (dt,J= 47.3, 4.5 Hz, 2H), 4.52-3.43 (m, 6H), 2.27 (d,J= 9.9 Hz, 3H). 434[M+H] + 190 (S)-1-(3-((1-(3-fluoropropyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO-d6) δ 10.63 (s, 1H), 7.15 (t,J= 3.2 Hz, 1H), 6.97 (s, 1H), 6.71- 6.50 (m, 2H), 6.38 (s, 1H), 6.15 (ddd,J= 16.7, 5.8, 2.3 Hz, 1H), 5.91 (d,J= 42.5 Hz, 1H), 5.66 (ddd,J= 25.8, 10.3, 2.3 Hz, 1H), 4.39 (dt,J= 47.3, 5.2 Hz, 2H), 4.22-3.48 (m, 6H), 2.45-2.03 (m, 7H). 430[M+H] + 191 1-((3S,4R)-3-fluoro-4-((1-(3-fluoropropyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, DMSO-d6) δ 11.21 (s, 1H), 7.27 (d,J= 2.9 Hz, 1H), 7.08 (d,J= 9.7 Hz, 1H), 6.81 (s, 1H), 6.64 (ddd,J= 16.6, 10.2, 6.3 Hz, 1H), 6.47 (dd,J= 8.3, 3.0 Hz, 1H), 6.21 (d,J= 16.7 Hz, 1H), 5.90-5.51 (m, 3H), 4.50-3.44 (m, 10H), 2.28 (d,J= 9.7 Hz, 3H), 2.20-2.03 (m, 2H). 448[M+H] + 192 (S)-1-(3-((6-((1H-pyrazol-3-yl)amino)-1-isopropyl-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO-d6) δ 11.99 (s, 1H), 8.61 (d,J= 4.9 Hz, 1H), 7.54 (s, 1H), 7.17 (s, 1H), 7.14 (s, 1H), 6.60 (ddd,J= 45.7, 16.7, 10.3 Hz, 1H), 6.29 (s, 1H), 6.18-6.08 (m, 2H), 5.67 (dd,J= 20.8, 11.4 Hz, 2H), 4.44 (sep,J= 6.6 Hz, 1H), 4.09-3.45 (m, 4H), 2.38-2.09 (m, 2H), 1.41 (d,J= 6.6 Hz, 6H). 381[M+H] + 193 (S)-1-(3-((1-isopropyl-6-((1-methyl-1H-pyrazol-3-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, DMSO-d6) δ 8.61 (d,J= 6.3 Hz, 1H), 7.48 (s, 1H), 7.13 (t,J= 3.2 Hz, 1H), 7.02 (d,J= 11.2 Hz, 1H), 6.59 (ddd,J= 45.8, 16.7, 10.3 Hz, 1H), 6.29 (s, 1H), 6.18-6.12 (m, 2H), 5.74-5.60 (m, 2H), 4.44 (sep,J= 6.6 Hz, 1H), 4.04-3.48 (m, 7H), 2.38-2.09 (m, 2H), 1.41 (d,J= 6.6 Hz, 6H). 395[M+H] + 194 (S)-1-(3-((1-isopropyl-6-((5-methyl-1H-pyrazol-3-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO-d6) δ 11.86 (s, 1H), 8.58 (d,J= 12.1 Hz, 1H), 7.22-7.05 (m, 2H), 6.60 (ddd,J= 44.5, 16.7, 10.3 Hz, 1H), 6.29 (d,J= 2.7 Hz, 1H), 6.15 (d,J= 16.7 Hz, 1H), 5.89 (d,J= 12.2 Hz, 1H), 5.74-5.60 (m, 2H), 4.44 (sep,J= 6.6 Hz, 1H), 4.07-3.47 (m, 4H), 2.39-2.09 (m, 5H), 1.41 (d,J= 6.6 Hz, 6H). 395[M+H] + 195 1-((3R,4S)-3-((6-((1H-pyrazol-3-yl)amino)-1-isobutyl-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-4-fluoropyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, DMSO-d6) δ 12.08 (s, 1H), 8.70 (s, 1H), 7.57 (d,J= 1.9 Hz, 1H), 7.17 (d,J= 4.9 Hz, 1H), 7.06 (t,J= 2.8 Hz, 1H), 6.64 (dt,J= 16.8, 9.7 Hz, 1H), 6.38-6.30 (m, 1H), 6.21 (dd,J= 16.7, 2.1 Hz, 1H), 6.08-6.00 (m, 1H), 5.75-5.44 (m, 3H), 4.49-3.21 (m, 6H), 2.17-2.04 (m, 1H), 0.85 (d,J= 6.6 Hz, 6H). 413[M+H] + 196 1-((3S,4R)-3-fluoro-4-((1-isobutyl-6-((5-methyl-1H-pyrazol-3-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO-d6) δ 11.91 (s, 1H), 8.62 (s, 1H), 7.17 (d,J= 2.2 Hz, 1H), 7.05 (t,J= 2.7 Hz, 1H), 6.64 (dt,J= 16.8, 10.3 Hz, 1H), 6.41-6.29 (m, 1H), 6.21 (dd,J= 16.7, 1.7 Hz, 1H), 5.86-5.47 (m, 4H), 4.48-3.22 (m, 6H), 2.18 (d,J= 2.4 Hz, 3H), 2.15-2.06 (m, 1H), 0.84 (d,J= 6.6 Hz, 6H). 427[M+H] + 197 1-((3S,4R)-3-fluoro-4-((1-isobutyl-6-((1-methyl-1H-pyrazol-3-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, DMSO-d6) δ 8.65 (s, 1H), 7.49 (t,J= 2.1 Hz, 1H), 7.12 (d,J= 3.4 Hz, 1H), 7.05 (t,J= 3.0 Hz, 1H), 6.70-6.58 (m, 1H), 6.36-6.28 (m, 1H), 6.21 (dd,J= 16.7, 1.9 Hz, 1H), 6.01 (dd,J= 3.4, 2.3 Hz, 1H), 5.75-5.41 (m, 3H), 4.43-3.31 (m, 9H), 2.15-2.06 (m, 1H), 0.86 (d,J= 6.6 Hz, 6H). 427[M+H] + 198 (S)-3-((4-((1-Acryloylpyrrolidin-3-yl)oxy)-1-isopropyl-1H-pyrrolo[3,2-c]pyridin-6-yl)amino)-1-methylpyridin- 2(1H)-1-one 1 H NMR (500 MHz, DMSO-d6) δ 8.10 (ddd,J= 19.7, 7.4, 1.3 Hz, 1H), 8.04 (d,J= 6.7 Hz, 1H), 7.23 (t,J= 3.0 Hz, 1H), 7.14 (dd,J= 6.7, 1.3 Hz, 1H), 6.94 (s, 1H), 6.60 (ddd,J= 47.2, 16.7, 10.3 Hz, 1H), 6.35 (s, 1H), 6.26 (t,J= 7.1 Hz, 1H), 6.14 (ddd,J= 16.7, 6.4, 2.3 Hz, 1H), 5.74-5.61 (m, 2H), 4.60-4.51 (m, 1H), 4.04-3.45 (m, 7H), 2.41-2.15 (m, 2H), 1.41 (d,J= 6.7 Hz, 6H). 422 [M+H] + 199 3-((4-(((3R,4S)-1-Acryloyl-4-fluoropyrrolidin-3-yl)oxy)-1-isobutyl-1H-pyrrolo[3,2-c]pyridin-6-yl)amino)-1-methylpyridin-2(1H)-one 1H NMR (500 MHz, DMSO-d6) δ 8.05 (d,J= 2.2 Hz, 1H), 7.95 (dd,J= 13.5, 7.4 Hz, 1H), 7.14 (dd,J= 8.4, 5.2 Hz, 2H), 6.99 (s, 1H), 6.67-6.57 (m, 1H), 6.42-6.33 (m, 1H), 6.27-6.13 (m, 2H), 5.76-5.45 (m, 3H), 4.35-3.41 (m, 6H), 3.53 (s, 3H), 2.15-2.05 (m, 1H), 0.84 (d,J= 6.6 Hz, 6H). 454 [M+H] + 200 1-(2-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-5-azaspiro[3.4]octan-5-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO) δ 7.19 - 7.15 (m, 1H), 7.04 (d,J= 24.0 Hz, 1H), 6.67 - 6.55 (m, 2H), 6.46 - 6.40 (m, 1H), 6.27 - 6.10 (m, 1H), 6.04 - 5.95 (m, 1H), 5.73 - 5.60 (m, 1H), 3.84 (t,J= 7.7 Hz, 3H), 2.32 (s, 3H), 2.23 - 2.17 (m, 2H), 2.13 - 2.05 (m, 4H), 1.85 - 1.72 (m, 3H), 0.85 (d,J= 6.6 Hz, 6H).466 [M+H] + 201 1-(7-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-1-azaspiro[4.4]nonan-1-yl)prop-2-en-1-one 1H NMR (500 MHz, DMSO) δ 7.12 (d,J= 3.2 Hz, 1H), 6.96 (s, 1H), 6.57 (s, 1H), 6.38 (d,J= 3.1 Hz, 1H), 6.12 (d,J= 7.7 Hz, 2H), 5.68 (d,J= 8.9 Hz, 2H), 3.87 (d,J= 7.4 Hz, 1H), 3.80 (d,J= 7.2 Hz, 3H), 2.36 (s, 1H), 2.30 (s, 3H), 2.19 - 2.01 (m, 5H), 1.85 (d,J= 12.1 Hz, 2H), 1.60 - 1.49 (m, 2H), 1.18 (s, 1H), 0.88 - 0.76 (m, 6H).480 [M+H] + 202 1-(2-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-6-azaspiro[3.4]octan-6-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO) δ 10.50 (s, 1H), 7.13 (s, 1H), 6.95 (d,J= 8.1 Hz, 1H), 6.62 - 6.47 (m, 2H), 6.37 (s, 1H), 6.13 (t,J= 14.6 Hz, 1H), 5.65 (d,J= 12.9 Hz, 2H), 3.81 (d,J= 6.9 Hz, 3H), 3.71 - 3.52 (m, 5H), 2.33 (d,J= 7.7 Hz, 3H), 2.23 - 1.91 (m, 6H), 0.84 (d,J=6.3 Hz, 6H).; 466[M+H] + 203 1-(2-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-5-azaspiro[3.5]nonan-5-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 6.95 (s, 1H), 6.87 (d,J= 2.8 Hz, 1H), 6.56 - 6.45 (m, 2H), 6.41 (s, 1H), 6.28 (d,J= 16.7 Hz, 1H), 5.68 - 5.54 (m, 2H), 3.79 (d,J= 7.3 Hz, 2H), 3.44 (s, 2H), 2.94 (dd,J= 14.3, 6.9 Hz, 2H), 2.52 (d,J= 13.2 Hz, 2H), 2.41 - 2.32 (m, 3H), 2.17 - 2.06 (m, 3H), 1.70 (s, 2H), 1.43 (s, 3H), 0.95 - 0.86 (m, 6H).; 480[M+H] + 204 1-(7-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)-2-azaspiro[4.4]nonan-2-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 6.94 (d,J= 5.4 Hz, 1H), 6.83 (d,J= 2.9 Hz, 1H), 6.50 - 6.33 (m, 4H), 5.86 (s, 1H), 5.67 (dd,J= 9.6, 2.8 Hz, 1H), 3.78 (d,J= 7.3 Hz, 2H), 3.64 - 3.44 (m, 4H), 2.39 (d,J= 13.1 Hz, 2H), 2.29 - 2.09 (m, 5H), 2.04 (t,J= 13.8 Hz, 3H), 1.99 - 1.87 (m, 2H), 0.92 (d,J= 6.6 Hz, 6H); 480 [M+H] +

[0815]

[0816] Example 205. Preparation of (S)-1-(3-((6-((5-methylthiazol-2-yl)amino)-1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one

[0817]

[0818]

[0819] Step 1. Preparation of tert-butyl (S)-3-((6-chloro-1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidine-1-carboxylate

[0820] 4,6-Dichloro-1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-c]pyridine (269 mg, 1.0 mmol) was dissolved in 1,4-dioxane (4.0 mL), and tert-butyl (S)-3-hydroxypyrrolidine-1-carboxylate (225 mg, 1.2 mmol), Pd2(dba)3 (46 mg, 0.05 mmol), (S)-(-)-BINAP (62 mg, 0.1 mmol), and Cs2CO3 (651 mg, 2.0 mmol) were added at room temperature. The reaction mixture was reacted at 130°C for 1 h using a microwave reactor. The mixture was diluted with ethyl acetate, washed with distilled water, and the organic layer was dried over MgSO4, filtered, concentrated, and the obtained residue was purified by silica gel chromatography (0-30% ethyl acetate / hexane) to synthesize tert-butyl (S)-3-((6-chloro-1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidine-1-carboxylate (268 mg, 64% yield) as a white solid.

[0821] 1 H NMR (500 MHz, CDCl3) δ 7.02-6.91 (m, 2H), 6.65 (d,J= 2.9 Hz, 1H), 5.76 (d,J= 18.8 Hz, 2H), 4.56 (q,J= 8.4 Hz, 2H), 3.77-3.48 (m, 4H), 2.22 (br s, 2H), 1.47 (d,J= 7.3 Hz, 9H).; LC-MS (ESI) m / z: 420 [M+H] +

[0822]

[0823] Step 2. Preparation of tert-butyl (S)-3-((6-((5-methylthiazol-2-yl)amino)-1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidine-1-carboxylate

[0824] Except that tert-butyl (S)-3-((6-chloro-1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidine-1-carboxylate was used instead of tert-butyl 4-(6-chloro-1-methyl-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridine-1(2H)-carboxylate used in the synthetic step 2 of the above Example 1, tert-butyl (S)-3-((6-((5-methylthiazol-2-yl)amino)-1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidine-1-carboxylate (39% yield) was prepared in the same manner as in step 2 of the above Example 1. It was synthesized.

[0825] 1 H NMR (500 MHz, CDCl3) δ 8.96 (s, 1H), 7.00 (d,J= 6.0 Hz, 1H), 6.87 (s, 1H), 6.59 (s, 1H), 6.40 (d,J= 13.6 Hz, 1H), 5.94 (d,J= 18.0 Hz, 1H), 4.52 (q,J= 8.4 Hz, 2H), 3.85-3.50 (m, 4H), 2.44-2.20 (m, 5H), 1.48 (d,J= 11.4 Hz, 8H).; LC-MS (ESI) m / z: 498 [M+H] +

[0826]

[0827] Step 3. Preparation of (S)-1-(3-((6-((5-methylthiazol-2-yl)amino)-1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one

[0828] In the same manner as in step 3 of the above Example 1, except that tert-butyl 4-(1-methyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridine-1(2H)-carboxylate was used instead of tert-butyl (S)-3-((6-((5-methylthiazol-2-yl)amino)-1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidine-1-carboxylate, the synthesis was carried out in step 3 of the above Example 1. (S)-1-(3-((6-((5-methylthiazol-2-yl)amino)-1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one (64% yield) was synthesized.

[0829] 1 H NMR (500 MHz, DMSO-d6)δ 10.73 (s, 1H), 7.17 (t,J= 2.6 Hz, 1H), 6.98 (s, 1H), 6.72 (d,J= 4.4 Hz, 1H), 6.60 (ddd,J= 50.6, 16.7, 10.3 Hz, 1H), 6.47 (s, 1H), 6.15 (ddd,J= 16.7, 7.3, 2.2 Hz, 1H), 5.91 (d,J= 42.8 Hz, 1H), 5.67 (ddd,J= 27.1, 10.3, 2.2 Hz, 1H), 5.05 (q,J= 9.1 Hz, 2H), 4.11-3.48 (m, 4H), 2.44-2.16 (m, 5H).; LC-MS (ESI) m / z: 452 [M+H] +

[0830]

[0831] Examples 206 to 223 were prepared in a similar manner to Example 205, and the structures and analysis results of the compounds are summarized and shown in Table 4 below.

[0832]

[0833] Example structural compound name 1 H NMR;LC-MS (ESI) m / z206 (S)-1-(3-((1-(2,2-difluoroethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 8.79 (s, 1H), 7.03-6.99 (m, 1H), 6.87 (dd,J= 7.3, 3.2 Hz, 1H), 6.65-6.33 (m, 4H), 6.00 (ddd,J= 58.9, 44.5, 4.0 Hz, 2H), 5.69 (ddd,J= 23.9, 9.4, 2.9 Hz, 1H), 4.35 (dd,J= 30.0, 14.5 Hz, 2H), 4.07-4.00 (m, 1H), 3.97-3.69 (m, 3H), 2.52-2.25 (m, 5H).; 434 [M+H] + 207 (R)-1-(2-(((6-((5-methylthiazol-2-yl)amino)-1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO-d6)δ 10.68 (d,J= 12.5 Hz, 1H), 7.19 (d,J= 3.2 Hz, 1H), 6.96 (s, 1H), 6.83-6.60 (m, 2H), 6.45 (dd,J= 20.2, 3.0 Hz, 1H), 6.14 (m, 1H), 5.62 (dd,J= 56.6, 12.1 Hz, 1H), 5.06 (dd,J= 18.2, 8.9 Hz, 2H), 4.75-4.44 (m, 3H), 3.76- 3.42 (m, 2H), 2.29 (s, 3H), 2.20-1.87 (m, 4H).; 466 [M+H] + 208 (R)-1-(2-(((6-((5-methylthiazol-2-yl)amino)-1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl)azetidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, DMSO-d6)δ 10.70 (d,J= 14.2 Hz, 1H), 7.20 (m, 1H), 6.97 (s, 1H), 6.72 (d,J= 10.1 Hz, 1H), 6.64-6.28 (m, 2H), 6.09 (d,J= 16.7 Hz, 1H), 5.63 (dd,J= 36.9, 10.3 Hz, 1H), 5.11-4.73 (m, 5H), 4.32- 3.83 (m, 2H), 2.38-1.93 (m, 5H).; 452 [M+H] + 209 (R)-1-(2-(((1-(2,2-difluoroethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl)azetidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 9.46 (s, 1H), 7.01 (d,J= 15.1 Hz, 1H), 6.91-6.83 (m, 1H), 6.60-6.19 (m, 4H), 6.14-5.84 (m, 1H), 5.65 (dd,J= 30.5, 10.1 Hz, 1H), 5.07-4.78 (m, 3H), 4.42-4.06 (m, 4H), 2.66-2.34 (m, 5H).; 434 [M+H] + 210 (R)-1-(2-(((1-(2,2-difluoroethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl)pyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 7.01 (d,J= 12.6 Hz, 1H), 6.89-6.80 (m, 1H), 6.75-6.25 (m, 4H), 5.97 (td,J= 55.1, 4.1 Hz, 1H), 5.64 (ddd,J= 37.5, 10.3, 1.3 Hz, 1H), 4.84 (t,J= 7.2 Hz, 1H), 4.72-4.45 (m, 2H), 4.30 (td,J= 13.9, 6.8 Hz, 2H), 3.82-3.56 (m, 2H), 2.33 (d,J=39.8 Hz, 3H), 2.21-2.06 (m, 1H).; 448 [M+H] + 211 1-((3S,4R)-3-fluoro-4-((6-((5-methylthiazol-2-yl)amino)-1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO-d6)δ 10.77 (s, 0.6H), 10.75 (s, 0.4H), 7.28-7.16 (m, 11H), 6.98 (s, 9H), 6.84 (d,J= 3.2 Hz, 9H), 6.64 (ddd,J= 16.7, 10.3, 2.7 Hz, 12H), 6.56-6.45 (m, 9H), 6.21 (d,J= 16.8 Hz, 10H), 5.89-5.54 (m, 30H), 5.17-5.01 (m, 18H), 4.49-4.42 (m, 6H), 4.28 (dd,J= 11.8, 7.6 Hz, 5H), 4.10-3.99 (m, 10H), 3.78 (ddd,J= 33.8, 22.2, 12.1 Hz, 25H), 3.51-3.43 (m, 14H), 2.28 (s, 9H), 2.26 (s, 13H).; 470 [M+H] + 212 1-((2R,4S)-2-methyl-4-((6-((5-methylthiazol-2-yl)amino)-1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one1 H NMR (500 MHz, CDCl3) δ 7.02 (d,J= 8.1 Hz, 1H), 6.88 (dd,J= 8.5, 3.2 Hz, 1H), 6.63-6.38 (m, 3H), 6.00 (m, 1H), 5.68 (ddd,J= 28.6, 9.4, 2.8 Hz, 3H), 4.57-4.47 (m, 2H), 4.36-4.08 (m, 2H), 3.98 (dd,J= 28.6, 13.3 Hz, 1H), 2.55 (m, 1H), 2.38 (s, 3H), 2.20 (m, 1H), 1.51 (d,J= 6.5 Hz, 3H).; 466 [M+H] + 213 1-((S)-3-((6-((5-methylthiazol-2-yl)amino)-1-((R)-1,1,1-trifluoropropan-2-yl)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 7.06-6.95 (m, 2H), 6.59 (m, 1H), 6.56-6.36 (m, 3H), 6.02 (m, 1H), 5.69 (ddd,J= 21.5, 9.4, 2.9 Hz, 2H), 4.77 (m, 1H), 4.05 (m, 1H), 3.97-3.73 (m, 3H), 2.54-2.25 (m, 5H), 1.76 (dd,J= 7.0, 3.6 Hz, 3H).; 466 [M+H] + 214 (R)-1-(3-(((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl )piperidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, DMSO) δ 10.49 (s, 1H), 7.13 (s, 1H), 6.94 (s, 1H), 6.86 - 6.68 (m, 1H), 6.61 (s, 1H), 6.40 (d,J= 17.7 Hz, 1H), 6.03 (t,J= 14.8 Hz, 1H), 5.68 - 5.47 (m,J= 36.9, 10.4 Hz, 1H), 4.56 - 4.36 (m, 2H), 4.03 - 3.77 (m, 4H), 3.17 - 3.05 (m, 1H), 2.34 (d,J= 23.5 Hz, 3H), 2.14 - 2.03 (m, 2H), 1.90 (s, 1H), 1.72 (s, 1H), 1.60 - 1.36 (m,J= 46.6, 19.8 Hz, 3H), 0.85 (d,J= 6.4 Hz, 6H).454[M+H] + 215 (S)-1-(3-(((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl )piperidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, DMSO) δ 10.49 (s, 1H), 7.13 (s, 1H), 6.94 (s, 1H), 6.83 - 6.68 (m, 1H), 6.61 (s, 1H), 6.40 (d,J= 17.3 Hz, 1H), 6.03 (t,J= 14.8 Hz, 1H), 5.68 - 5.47 (m, 1H), 4.56 - 4.40 (m, 2H), 3.98 - 3.80 (m, 4H), 3.16 - 3.08 (m, 1H), 2.31 (s, 3H), 2.13 - 2.02 (m, 2H), 1.90 (s, 1H), 1.77 - 1.35 (m, 4H), 0.85 (d,J= 6.4 Hz, 6H).454[M+H] + 216 (S)-1-(3-(((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl)pyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, DMSO) δ 10.50 (s, 1H), 7.13 (s, 1H), 6.94 (s, 1H), 6.66 - 6.53 (m, 2H), 6.39 (d,J= 8.0 Hz, 1H), 6.12 (d,J= 16.8 Hz, 1H), 5.69 - 5.58 (m, 1H), 4.64 - 4.50 (m, 2H), 3.82 (d,J= 7.1 Hz, 2H), 3.72 (s, 1H), 3.67 - 3.52 (m, 3H), 2.30 (s, 3H), 2.18 - 1.76 (m, 4H), 0.84 (d,J= 6.2 Hz, 6H).440[M+H] + 217 1-(2-(((1-cyclopentyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 7.00 (d,J= 10.1 Hz, 1H), 6.96 - 6.91 (m, 1H), 6.55 - 6.34 (m, 4H), 5.70 - 5.56 (m, 1H), 4.90 - 4.80 (m, 1H), 4.72 - 4.45 (m, 3H), 3.81 - 3.55 (m, 2H), 2.37 (d,J= 7.2 Hz, 3H), 2.33 - 2.23 (m, 1H), 2.22 - 2.05 (m, 5H), 1.83 (d,J= 61.2 Hz, 6H).452[M+H] + 218 1-(2-(((1-Cyclopentyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl)azetidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 7.08 - 6.89 (m, 2H), 6.62 - 6.18 (m, 4H), 5.75 - 5.52 (m, 1H), 5.09 - 4.80 (m, 3H), 4.64 - 4.51 (m, 1H), 4.36 - 4.04 (m, 2H), 2.64 - 2.42 (m, 2H), 2.38 (s, 3H), 2.18 (d,J= 6.2 Hz, 3H), 1.83 (d,J= 61.2Hz,5H). 438[M+H] + 219 (S)-1-(2-(((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 9.91 (s, 1H), 7.03-6.91 (m, 2H), 6.78-6.46 (m, 3H), 5.74-5.59 (m, 4H), 4.82 (ddd,J= 15.5, 10.6, 3.8 Hz, 1H), 4.73-4.45 (m, 3H), 3.78-3.59 (m, 2H), 2.41-1.94 (m, 7H), 1.49 (s, 6H). 426[M+H] + 220 (S)-1-(2-(((1-(cyclopentylmethyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl)pyrrolidin-1-yl)prop-2-en-1-one 1H NMR (500 MHz, CDCl3) δ 7.02 (d,J= 9.5 Hz, 3H), 6.85 (d,J= 3.1 Hz, 3H), 6.62 (ddd,J= 102.4, 16.7, 10.3 Hz, 4H), 6.47 - 6.31 (m, 9H), 5.63 (dd,J= 37.1, 10.4 Hz, 3H), 4.91 - 4.79 (m, 3H), 4.73 - 4.45 (m, 7H), 3.92 - 3.83 (m, 6H), 3.79 - 3.57 (m, 7H), 2.38 (d,J= 8.4 Hz, 11H), 2.30 (dd,J= 19.5, 8.8 Hz, 3H), 2.13 (ddd,J= 30.5, 20.7, 7.8 Hz, 9H), 2.01 - 1.89 (m, 4H), 1.68 (s, 14H), 1.57 (s, 7H), 1.25 (s, 8H).; 466[M+H] + 221 1-((2S)-2-(((1-(2-methylbutyl)-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 7.01 (d,J= 10.6 Hz, 1H), 6.82 (s, 1H), 6.61 (ddd,J= 102.3, 16.6, 10.3 Hz, 1H), 6.46 - 6.31 (m, 3H), 5.64 (dd,J= 37.6, 10.2 Hz, 1H), 4.90 - 4.78 (m, 1H), 4.73 - 4.45 (m, 2H), 3.96 - 3.85 (m, 1H), 3.80 - 3.56 (m, 3H), 2.38 (d,J= 8.1 Hz, 3H), 2.30 (dd,J= 18.4, 9.1 Hz, 1H), 2.17 - 2.07 (m, 2H), 2.02 - 1.86 (m, 2H), 1.48 - 1.34 (m, 1H), 1.19 (d,J= 6.7 Hz, 1H), 0.97 - 0.80 (m, 6H).; 454[M+H] + 222 (S)-1-(2-(((1-cyclopentyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl)pyrrolidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 7.02 (d,J= 8.8 Hz, 1H), 6.93 (dd,J= 6.6, 3.2 Hz, 1H), 6.75 - 6.35 (m, 4H), 5.70 - 5.57 (m, 1H), 4.89 - 4.81 (m, 1H), 4.71 - 4.47 (m, 3H), 3.77 - 3.58 (m, 2H), 2.38 (d,J= 7.5 Hz, 3H), 2.31 - 2.09 (m, 6H), 1.91 - 1.73 (m, 6H).452[M+H] + 223 (R)-1-(2-(((1-cyclopentyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)methyl)azetidin-1-yl)prop-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 7.03 (d,J= 12.5 Hz, 1H), 6.92 (d,J= 8.7 Hz, 1H), 6.64 - 6.15 (m, 4H), 5.69 - 5.53 (m, 1H), 5.05 - 4.82 (m, 3H), 4.62 - 4.06 (m, 3H), 2.37 (s, 3H), 2.19 (d,J= 45.4 Hz, 3H), 1.81 (d,J= 63.4 Hz, 7H).438[M+H] +

[0834]

[0835] Example 224. Preparation of (S)-2-fluoro-1-(3-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one

[0836]

[0837]

[0838] Step 1. Preparation of tert-butyl (S)-3-((6-chloro-1-isopropyl-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidine-1-carboxylate

[0839] Tert-Butyl (S)-3-hydroxypyrrolidine-1-carboxylate (1.76 g, 9.4 mmol) was dissolved in THF (10.0 mL), and 60% NaH (469 mg, 11.2 mmol) was slowly added at 0°C. The reaction mixture was stirred at 0°C for 30 minutes, after which 4,6-dichloro-1-isopropyl-1H-pyrrolo[3,2-c]pyridine (1.90 g, 7.8 mmol) was added, and the reaction was carried out at 60°C for 6 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate, and washed with aqueous ammonium chloride solution. The organic layer was dried over MgSO4, filtered, concentrated, and the resulting residue was purified by silica gel chromatography (0-30% ethyl acetate / hexane) to synthesize tert-butyl (S)-3-((6-chloro-1-isobutyl-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidine-1-carboxylate (2.00 g, 65% yield) as a white solid.

[0840] 1 H NMR (500 MHz, DMSO-d6)δ 7.40-7.27 (m, 2H), 6.48 (s, 1H), 5.57 (d,J= 23.4 Hz, 1H), 3.96 (d,J= 7.3 Hz, 2H), 3.70-3.56 (m, 2H), 3.45 (d,J= 9.1 Hz, 2H), 2.26-2.00 (m, 3H), 1.39 (d,J= 12.5 Hz, 9H), 0.81 (d,J= 6.6 Hz, 6H).; LC-MS (ESI) m / z: 394 [M+H] +

[0841]

[0842] Step 2. Preparation of tert-butyl (S)-3-((1-isopropyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidine-1-carboxylate

[0843] Except that tert-butyl (S)-3-((6-chloro-1-isobutyl-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidine-1-carboxylate was used instead of tert-butyl 4-(6-chloro-1-methyl-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridine-1(2H)-carboxylate used in step 2 of the above-mentioned example 1, tert-butyl (S)-3-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidine-1-carboxylate was used in the same manner as in step 2 of the above-mentioned example 1, to synthesize tert-butyl (S)-3-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidine-1-carboxylate (42% yield).

[0844] LC-MS (ESI) m / z: 472 [M+H] +

[0845]

[0846] Step 3. Preparation of (S)-2-fluoro-1-(3-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one

[0847] tert-Butyl (S)-3-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidine-1-carboxylate (118 mg, 0.25 mmol) was dissolved in CH2Cl2 (2.0 mL), TFA (1.5 mL) was added, and the mixture was stirred at room temperature for 1 h. After the reaction was completed, the mixture was concentrated under reduced pressure to synthesize a salt compound. The obtained salt compound was dissolved in DMF (2.0 mL), and DIPEA (0.28 mL, 1.6 mmol), 2-fluoroacrylic acid (34 mg, 0.38 mmol), and HATU (115 mg, 0.30 mmol) were added, and the mixture was stirred at room temperature for 15 h. The reaction mixture was diluted with ethyl acetate and washed with distilled water and brine. The organic layer was dried over MgSO4, filtered, and concentrated, and the resulting residue was purified by silica gel chromatography (70% ethyl acetate / hexane) to synthesize (S)-2-fluoro-1-(3-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one (45 mg, 41% yield) as a white solid.

[0848] 1 H NMR (500 MHz, CDCl3) δ 7.05 (d,J= 4.5 Hz, 1H), 6.83 (s, 1H), 6.48-6.43 (m, 1H), 6.41 (d,J= 5.1 Hz, 1H), 6.02 (d,J= 18.7 Hz, 1H), 5.56 (dd,J= 46.8, 2.9 Hz, 1H), 5.13 (ddd,J= 22.1, 16.1, 2.8 Hz, 1H), 4.18-3.67 (m, 6H), 2.53-2.22 (m, 5H), 2.15 (m, 1H), 0.93 (dd,J= 6.3, 1.8 Hz, 6H).; LC-MS (ESI) m / z: 444 [M+H] +

[0849]

[0850] Examples 225 to 231 were prepared in a similar manner to Example 224, and the structures and analysis results of the compounds are summarized and shown in Table 5 below.

[0851]

[0852] Example structural compound name 1 H NMR;LC-MS (ESI) m / z225 (S)-1-(3-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-yn-1-one 1H NMR (500 MHz, CDCl3) δ 7.04 (d,J= 9.2 Hz, 1H), 6.85 (dd,J= 5.8, 3.2 Hz, 1H), 6.47 (t,J= 3.3 Hz, 1H), 6.42 (d,J= 8.8 Hz, 1H), 6.02 (m, 1H), 4.15-3.69 (m, 6H), 3.08 (s, 0.5H), 3.01 (s, 0.5 H), 2.50-2.30 (m, 5H), 2.15 (m, 1H), 0.93 (t,J= 5.7 Hz, 6H).; 424 [M+H] + 226 (S,E)-1-(3-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)but-2-en-1-one 1 H NMR (500 MHz, CDCl3) δ 7.05-6.81 (m, 3H), 6.53-6.40 (m, 2H), 6.15 (dd,J= 55.4, 15.0 Hz, 1H), 5.99 (m, 1H), 4.09-3.69 (m, 6H), 2.58-2.08 (m, 6H), 1.88 (dd,J= 25.1, 6.6 Hz, 3H), 0.97-0.87 (m, 6H).; 440 [M+H] + 227 (S,E)-4-(dimethylamino)-1-(3-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)but-2-en-1-one1 H NMR (500 MHz, CDCl3) δ 10.60 (br s, 1H), 7.02 (d,J= 12.7 Hz, 1H), 6.94 (m, 1H), 6.82 (m, 1H), 6.50-6.41 (m, 2H), 6.31 (dd,J= 60.6, 15.2 Hz, 1H), 6.03 (m, 1H), 4.07-3.50 (m, 6H), 3.09 (dd,J= 26.3, 5.9 Hz, 2H), 2.55-2.10 (m, 12H), 0.97-0.89 (m, 6H).; 483 [M+H] + 228 N-(4-(((3R,4S)-4-fluoro-1-(vinylsulfonyl)pyrrolidin-3-yl)oxy)-1-isobutyl-1H-pyrrolo[3,2-c]pyridin-6-yl)-5-methylthiazol-2-amine1H NMR (500 MHz, DMSO) δ 10.57 (s, 1H), 7.18 (d, J = 3.1 Hz, 1H), 7.02 - 6.94 (m, J = 17.0, 9.5 Hz, 2H), 6.76 (s, 1H), 6.40 (d, J = 3.0 Hz, 1H), 6.23 - 6.14 (m, 2H), 5.81 - 5.68 (m, 1H), 5.60 (d, J = 54.3 Hz, 1H), 4.07 - 4.00 (m, 1H), 3.84 (d, J = 7.2 Hz, 2H), 3.74 - 3.59 (m, 2H), 3.38 (d, J = 9.4 Hz, 1H), 2.32 (s, 2H), 2.12 - 2.04 (m, 1H), 0.84 (d, J = 6.5 Hz, 6H).480[M+H]+229 2-Chloro-1-((3S,4R)-3-fluoro-4-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)ethan-1-one 1H NMR (500 MHz, DMSO) δ 10.82 (s, 1H), 7.21 (s, 1H), 7.01 (s, 1H), 6.79 (d, J = 4.4 Hz, 1H), 6.42 (s, 1H), 5.92 - 5.55 (m, 2H), 4.45 - 4.23 (m, 3H), 4.08 - 3.95 (m, 1H), 3.88 - 3.67 (m, 4H), 2.30 (s, 3H), 2.12 - 2.04 (m, J = 13.2, 6.6 Hz, 1H), 0.85 (d, J = 6.4 Hz, 6H).466[M+H]+230 1-((3S,4R)-3-fluoro-4-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)but-2-yn-1-one 1H NMR (500 MHz, DMSO) δ 10.56 (d, J = 12.1 Hz, 1H), 7.18 (s, 1H), 6.97 (s, 1H), 6.76 (s, 1H), 6.40 (s, 1H), 5.84 - 5.55 (m, 2H), 4.57 - 4.42 (m, 1H), 4.25 - 3.98 (m, 2H), 3.87 - 3.61 (m, 6H), 2.29 (s, 3H), 2.11 - 2.06 (m, 1H), 0.85 (d, J = 6.5 Hz, 6H).456[M+H]+231 1-((3S,4R)-3-fluoro-4-((1-isobutyl-6-((5-methylthiazol-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-yn-1-one 1H NMR (500 MHz, DMSO) δ 10.91 (s, 1H), 7.22 (d, J = 2.9 Hz, 1H), 7.03 (d, J = 3.4 Hz, 1H), 6.79 (d, J = 7.4 Hz, 1H), 6.43 (s, 1H), 5.88 - 5.54 (m, 3H), 4.66 - 4.49 (m, 2H), 4.37 (s, 1H), 3.86 (d, J = 7.3 Hz, 3H), 2.30 (s, 3H), 2.14 - 2.04 (m, J = 13.4, 6.7 Hz, 1H), 0.85 (d, J = 6.6 Hz, 6H).442[M+H]+

[0853] Experimental example: Inhibitory activity against BTK and ITK

[0854] The inhibitory activity of the compounds prepared in the above examples against BTK and ITK was measured as follows.

[0855]

[0856] Inhibitory activity against BTK and ITK was assessed using Promega's 'ADP-Glo™ Kinase Assay'. This assay quantifies the amount of ADP produced during the kinase reaction to measure activation, and was used to measure inhibitory activity against BTK and ITK.

[0857] Specifically, the inhibitory activity against BTK and ITK kinases was measured using BTK kinase (Signalchem, B10-10H) and ITK kinase (Signalchem, I13-11G-10) and ADP-Glo ​​kinase assay kits (Promega, V9102). Recombinant purified human BTK and ITK were diluted in 1 x kinase reaction buffer (40 mM Tris-Cl, pH 7.5, 20 mM MgCl2, 0.1 mg / mL BSA, 2 mM MnCl2, and 50 uM DTT) (ITK: final concentration 4 ng per reaction / BTK: final concentration 10 ng per reaction) and added to a 96-well plate. The compounds of the previously prepared examples were finally treated to make a 1% DMSO aqueous solution, and the enzymatic reaction was initiated by adding a substrate cocktail containing ATP (1 mM or Km ATP (BTK: 10 uM / ITK: 25 uM)) and 0.2 ug / ul of Poly (Glu4,Tyr1) peptide (final concentration of BTK and ITK) in a total of 25 uL of the reaction to a 96-well plate. After 1 hour of incubation (30°C), an equal volume (25 uL per reaction) of ADP Glo was added and incubated at room temperature (30°C) for 40 minutes. Subsequently, kinase detection reagent (45 uL per reaction) was added and incubated at room temperature (30°C) for 30 minutes. Kinase activity was measured by chemiluminescence according to the ADP Glo kinase assay kit instructions, and the inhibitory activity of the compounds according to the present invention was calculated. The results of each compound were analyzed using Microsoft Excel, and IC 50 Values ​​were calculated by GraphPad Prism software.

[0858]

[0859] Derived IC 50Depending on the range of values, the inhibitory activity of each compound was classified into A, B, C, and D, and is shown in Table 6 below.

[0860] A: Derived IC 50 If the value is less than 20 nM

[0861] B: Derived IC 50 If the value is greater than 20 nM and less than or equal to 100 nM

[0862] C: Derived IC 50 If the value is greater than 100 nM and less than or equal to 500 nM

[0863] D: Derived IC 50 If the value exceeds 500 nM

[0864]

[0865] Example ITK IC 50 (nM)BTK IC 50 (nM) Example ITK IC 50 (nM)BTK IC 50

Claims

DEPCT691. Compounds represented by the following chemical formula 1 or their pharmaceutically acceptable salts: [Chemical Formula 1](Chemical Formula) In Chemical Formula 1, Y1 is a single bond, C1-4 alkylene or C1-4 haloalkylene; R1 is C1-10 alkyl, C1-10 alkoxy, C3-10 cycloalky, C6-20 aryl, heteroaryl with 6 members containing N, tetrahydrofuranil or tetrahydropyranil in which R1 is unsubstituted or substituted by one or more substituents chosen from halogenated, cyanogenic, hydroxyl, C1-4 alkyl groups. And C1-4 haloalkyl A is a benzene ring or heterocycle with 5 or 6 members, consisting of 1 to 3 heteroatoms selected from a group of N, O, and S that are substituted or not substituted with oxo(=O), provided that the 5 or 6-member heterocycle contains at least one N atom. Each R2 is independent, either hydrogen, halogen, cyano, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, or -CONH(C1-4 alkyl). k is 1 or 2, Y2 is a single bond, -O-, or -O-(C1-4 alkylene).L is one of the linking groups represented by the following chemical formulas 2a through 2k: (chemical formula) (chemical formula) (chemical formula) (chemical formula) 2a 2b 2c 2d (chemical formula) (chemical formula) (chemical formula) 2e 2f 2g (chemical formula) (chemical formula) (chemical formula) (chemical formula) 2h 2i 2j 2k. In chemical formulas 2a through 2k, n is 0, 1, 2, or 3; each Z is independent and represents a halogen, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, or C1-4 haloalkoxy; each a is independent and represents 0, 1, or 2; L' is methylene, ethylene, or methylene-O-methylene; each v and w are independent and represent 0, 1, or 2, provided that v + w are integers. From 0 to 3, each p to s is independent of each other, i.e., 0, 1, 2, 3, or 4, provided that each p+q and r+s are independent of each other, i.e., integers from 2 to 4. * means the point connected to Y2 in the chemical formula 1. X is CO or SO2, and R3 is C1-4 alkyl, C2-4 alkynyl, or C2-4 alkynyl where R3 is not substituted or is substituted by one or more substituents chosen from the halogen, NH2, NH(C1-4 alkyl), and N(C1-4 alkyl) groups.

22. Its pharmaceutically acceptable compound or salt as claimed in claim 1, where: Y1 is a single bond,Methylene or ethylene3. Its pharmaceutically acceptable compounds or salts as claimed in claim 1, where: R1 is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, secondary-butyl, tertiary-butyl, n-pentyl, isopentyl, n-hexyl, isohexyl, methoxy, ethoxy, propoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, pyridinyl, tetrahydrofuranil or tetrahydro-pyranil, where R1 is not substituted or is substituted by 1 to 3 substituents selected from the group comprising cl A is benzene, thiazole, thiadiazole, imidazole, pyrazole, pyrazine, pyridine, pyrimidine, or the pyridine-2(1H)-ion ring. R2 is hydrogen, chloro, fluoro, cyano, methyl, monofluoromethyl, difluoromethyl, trifluoromethyl,6. Its pharmaceutically acceptable compounds or salts as claimed in Claim 1 where: Y2 is a single bond, -O- or -O- (methylene).

7. Its pharmaceutically acceptable compounds or salts as claimed in Claim 1 where: when Y2 is a single bond, L is any linking group represented by the chemical formula 2a to 2g.

8. Its pharmaceutically acceptable compounds or salts as claimed in Claim 1 where: when Y2 is -O- or -O- (C1-4 alkali). L is one of the linking groups represented by the chemical formulas 2h to 2k9. Its pharmaceutically acceptable compound or salt as claimed in Claim 1, where: L is one of the linking groups chosen from the groups represented as follows: (chemical formula) where Z and a are as defined in Claim 1 and * denotes a point linked to Y2 in the chemical formula110. Its pharmaceutically acceptable compound or salt as claimed in Claim 1, where: Z is chloro, fluoro,Methyl or methoxy11. Its pharmaceutically acceptable compound or salt as claimed in claim 1 where:R3 is -CH3,-CH=CH2,-CH=CHCH3,-C bond 3CH, or -C bond 3CCH3 where R3 is unsubstituted or substituted by one or two substituents chosen from the chloro, fluoro, NH2, NH(methyl) and N(methyl)2 groups.

12. Its pharmaceutically acceptable compound or salt as claimed in claim 1 where:The compound represented by chemical formula 1 is represented by one of the following chemical formulas 1-1 to 1-3: [chemical formula 1-1](chemical formula 1-1) (Chemical Formula 1-2)(Chemical Formula)[Chemical Formula 1-3](Chemical Formula) in Chemical Formula 1-1 to 1-3 R'2 is halogen, cyano, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy or -CONH(C1-4 alkyl). Y1, R1, R2, Y2, L and R3 are as defined in Claim 113. The pharmaceutically acceptable compound or its salt as claimed in Claim 1, where: The compound represented by Chemical Formula 1 is any one of the compounds chosen from the group consisting of: 1) 1-(4-(1-methyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-il)prop-2-n-1-one,2)1-(4-(1-isopropyl-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)-3,6-dihydropyridin-1(2H)-il)prop-2-n-1-one,3)1-(3-(1-methyl-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3, 2-c]pyridin-4-il)-2,5-dihydro-1H-pyrrolo-1-il)prop-2-N-1-ONE,4)1-(4-(1-(cyclopropylmethyl)-6-((5-methylthiazole-2-il)amino)-1H-pyrrolo[3,2-c]pyridin-4-il)-3,6-dihydropyridin-1(2H)-il)prop-2-N-1-ONE,5)1-(4-(1-cyclopentyl-6-((5-methylthiazole-2-il)amino)-1H-pyrrolo Azole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)-3,6-dihydropyridin-1(2H)-il)prop-2-n-1-one,6)1-(4-(1-isobutyl-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)-3,6-dihydropyridin-1(2H)-il)prop-2-n-1-one,7)1-(4-(1 -(cyclobutylmethyl)-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one,8)1-(4-(6-((5-methylthiazole-2-yl)amino)-1-((tetrahydrofuran-3-yl)methyl)-1H-pyrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-il)prop-2-n-1-one,9)1-(4-(1-(cyclohexylmethyl)-6-((5-methylthiazole-2-il)amino)-1H-pyrrolo[3,2-c]pyridin-4-il)-3,6-dihydropyridin-1(2H)-il)prop-2-n-1-one,10)1-(4-(1-(cyclopentylmethyl)-6-((5-methylthiazole-2-il)amino )-1H-pyrolo[3,2-c]pyridin-4-il)-3,6-dihydropyridin-1(2H)-il)prop-2-n-1-one,11)1-(4-(1-((4,4-difluorocyclohexyl)methyl)-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)-3,6-dihydropyridin-1(2H)-il)prop-2-n-1-one,12)1-(4-( 1-(2,2-difluoroethyl)-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)-3,6-dihydropyridin-1(2H)-il)prop-2-en-1-one,13)(S)-1-(4-(1-(secondary-butyl)-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)-3,6-dihydropyridin Pyridin-1(2H)-il)prop-2-N-1-one,14)(R)-1-(4-(1-(secondary-butyl)-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)-3,6-dihydropyridin-1(2H)-il)prop-2-N-1-one,15)1-(4-(1-benzyl-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,[3,2-c]pyridin-4-il)-3,6-dihydropyridin-1(2H)-il)prop-2-n-1-one,16)1-(4-(6-((5-methylthiazole-2-il)amino)-1-phenethyl-1H-pyrrolo[3,2-c]pyridin-4-il)-3,6-dihydropyridin-1(2H)-il)prop-2-n-1-one,17)1-(4-(6-((5-methylthiazole-2-il)amino)-1-( (1-(trifluoromethyl)cyclopropyl)methyl)-1H-pyrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-n-1-one,18)1-(4-(1-(3,3-dimethylbutyl)-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl )prop-2-n-1-one,19)1-(4-(6-((5-methylthiazole-2-il)amino)-1-(2,2,2-trifluoroethyl)-1H-pyrolo[3,2-c]pyridin-4-il)-3,6-dihydropyridin-1(2H)-il)prop-2-n-1-one,20)1-(4-(1-(2,2-difluorocyclopropyl)-6-((5-methylthiazole-2-il)amino)-1H-pyrolo Pyrrolol[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-n-1-one,21)1-(4-(1-(difluoromethyl)-6-((5-methylthiazole-2-yl)amino)-1H-pyrrolol[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-n-1-one,22)2-(4-(1-acryloyl-1,2,3,6-tetrahydropyridin-4-il)-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-1-il)-2-methylpropanitrile,23)2-(4-(1-acryloyl-1,2,5,6-tetrahydropyridin-3-il)-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-1-il)-2-methylpropanitrile Trile,24)(R)-1-(4-(6-((5-methylthiazole-2-yl)amino)-1-(1,1,1-trifluoropropane-2-yl)-1H-pyrrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one,25)1-(4-(1-(2,2-difluoroethyl)-6-((5-methylthiazole-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin Ridin-4-il)-3-methyl-3,6-dihydropyridin-1(2H)-il)prop-2-N-1-one,26)1-(4-(1-isopropyl-6-((5-methylthiazole-2-il)amino)-1H-pyrrolo[3,2-c]pyridin-4-il)-2,3,6,7-tetrahydro-1H-acepin-1-il)prop-2-N-1-one,27)1-(7-(1-isopropyl-6-((5-methylthiazole -2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)-3-oxa-9-azabicyclo[3.3.1]non-6-en-9-il)prop-2-en-1-one,28)1-(3-(1-methyl-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)-8-azabicyclo[3.2.1]oxt-2-en-8-il)prop-2-en-1-one,29)1-(3-(1-isopropyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)-8-azabicyclo[3.2.1]oct-2-en-8-yl)prop-2-en-1-one,30)1-(3-(6-((5-methylthiazole-2-yl)amino)-1-((1-(trifluoromethyl)cyclopropyl)methyl)-1H-pyrolo[3,2-c]pyridin Pyridin-4-il)-8-azabicyclo[3.2.1]Oct-2-N-8-il)prop-2-N-1-one31)1-(3-(1-(2,2-difluorocyclopropyl)-6-((5-methylthiazole-2-il)amino)-1H-pyrrolo[3,2-c]pyridin-4-il)-8-azabicyclo[3.2.1]Oct-2-N-8-il)prop-2-N-1-one,32)1-(3-(1-isobutyl-6- ((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)-8-azabicyclo[3.2.1]oct-2-en-8-yl)prop-2-en-1-one,33)1-(3-(1-cyclopentyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)-8-azabicyclo[3.2.1]oct-2-en-8-yl)prop Prop-2-N-1-ONE,34)1-(3-(1-(2,2-difluoroethyl)-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)-8-azabicyclo[3.2.1]Oct-2-N-8-yl)prop-2-N-1-ONE,35)1-(3-(6-((5-methylthiazole-2-yl)amino)-1-(2,2,2-trifluoroethyl)-1H-pyrolo3,2-c]pyridin-4-il)-8-azabicyclo[3.2.1]oct-2-en-8-il)prop-2-en-1-one,36)1-(3-(1-methyl-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)-9-azabicyclo[3.3.1]non-2-en-9-il)prop-2-en-1-one,37)1-(3-(1-isopropyl-6-((5-methylthiazole-2-il)amino)-1H-pyrrolo[3,2-c]pyridin-4-il)-9-azabicyclo[3.3.1]non-2-en-9-il)prop-2-en-1-one,37)1-(3-(1-isopropyl-6-((5-methylthiazole-2-il)amino)-1H-pyrrolo Azole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)-9-azabicyclo[3.3.1]non-2-en-9-il)prop-2-en-1-one,38)1-(3-(1-isobutyl-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)-9-azabicyclo[3.3.1]non-2-en-9-il)prop-2-en-1-one n,39)1-(3-(1-(cyclopropylmethyl)-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)-8-azabicyclo[3.2.1]oct-2-en-8-yl)prop-2-en-1-one,40)1-(4-(6-((1H-imidazole-2-yl)amino)-1-methyl-1H-pyrolo[3,2-c]pyridin-4-yl)-3,6-dihydropy pyridin-1(2H)-il)prop-2-n-1-one,41)1-(4-(1-isopropyl-6-((5-methyl-1,3,4-thiadiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)-3,6-dihydropyridin-1(2H)-il)prop-2-n-1-one,42)1-(4-(1-isopropyl-6-((4-methylthiazole-2-il)amino)-1H-pyrolo[3,[3,2-c]pyridin-4-il)-3,6-dihydropyridin-1(2H)-il)prop-2-n-1-one,43)1-(4-(1-isopropyl-6-(pyrimidin-4-ilamino)-1H-pyrrolo[3,2-c]pyridin-4-il)-3,6-dihydropyridin-1(2H)-il)prop-2-n-1-one,44)1-(4-(1-isopropyl-6-((6-methylpyrimidin-4-il)amino N)-1H-pyrolo[3,2-c]pyridin-4-il)-3,6-dihydropyridin-1(2H)-il)prop-2-N-1-ONE,45)1-(4-(1-isopropyl-6-((6-(trifluoromethyl)pyrimidin-4-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)-3,6-dihydropyridin-1(2H)-il)prop-2-N-1-ONE,46)1-(4-(1-isopropyl Isopropyl-6-((6-methoxypyrimidin-4-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)-3,6-dihydropyridin-1(2H)-il)prop-2-en-1-one,47)1-(4-(6-((4-fluoropyridin-2-il)amino)-1-isopropyl-1H-pyrolo[3,2-c]pyridin-4-il)-3,6-dihydropyridin-1(2H)-il)prop- 2-N-1-ONE,48)1-(4-(1-isopropyl-6-((4-(trifluoromethyl)pyridin-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-N-1-ONE,49)1-(4-(1-isopropyl-6-((4-methylpyridin-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)-3,6-dihydropyridin-1(2H)-il)prop-2-n-1-one,50)N-(3-(1-methyl-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)phenyl)acrylamide,51)N-(2-fluoro-3-(1-methyl-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)phenyl)acrylamide Acrylamide,52)N-(2-methoxy-3-(1-methyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide,53)N-(3-methyl-5-(1-methyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide,54)N-(2-fluoro-5-(1 -methyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide,55)N-(2-methyl-5-(1-methyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide,56)N-(2,6-dimethyl-3-(1-methyl-6-((5-methylthiazole- 2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)phenyl)acrylamide,57)N-(2,6-difluoro-3-(1-methyl-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)phenyl)acrylamide,58)N-(3-(1-isopropyl-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)-2-methylphenyl)acrylamide,59)N-(4-fluoro-3-(1-isopropyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide,60)N-(2,4-difluoro-5-(1-isopropyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin N-(3-(1-(cyclopropylmethyl)-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)-4-fluorophenyl)acrylamide,62)N-(3-(1-isobutyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)-2-methylphenyl L) Acrylamide,63)N-(4-fluoro-3-(1-isobutyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide,64)N-(5-(1-(cyclopropylmethyl)-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)-2-fluorophenyl)acrylamide 65)N-(5-(1-(cyclopropylmethyl)-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)-2-methylphenyl)acrylamide,66)N-(5-(1-(cyclopropylmethyl)-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)-2,4-difluorophenyl)acrylamide,67)N-(2,4-difluoro-5-(1-isobutyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide,68)(S)-N-(3-(1-(secandary-butyl)-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)-4-fluorophenyl)acrylamide 69)N-(5-(1-(3,3-dimethylbutyl)-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)-2,4-difluorophenyl)acrylamide,70)N-(3-(1-cyclopentyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)-4-fluorophenyl)acrylamide ,71)N-(4-fluoro-3-(6-((5-methylthiazole-2-il)amino)-1-((tetrahydrofuran-3-il)methyl)-1H-pyrolo[3,2-c]pyridin-4-il)phenyl)acrylamide,72)N-(2-fluoro-5-(6-((5-methylthiazole-2-il)amino)-1-((tetrahydrofuran-3-il)methyl)-1H-pyrolo[3,2-c]pyridin-4-il)phenyl)acrylamide Pyridin-4-il)phenyl)acrylamide,73)N-(2-fluoro-3-(6-((5-methylthiazole-2-il)amino)-1-((tetrahydro-2H-pyran-4-il)methyl)-1H-pyrolo[3,2-c]pyridin-4-il)phenyl)acrylamide,74)N-(5-(1-(2,2-difluoroethyl)-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)-2-methylphenyl)acrylamide,75)N-(3-(1-(2,2-difluoroethyl)-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)-4-fluorophenyl)acrylamide,76)N-(5-(1-(2,2-difluoroethyl)-6-((5-methylthiazole-2-il)amino)-1H- Pyrolo[3,2-c]pyridin-4-il)-2-fluorophenyl)acrylamide,77)N-(2,4-difluoro-5-(6-((5-methylthiazole-2-il)amino)-1-(2,2,2-trifluoroethyl)-1H-pyridin-4-il)phenyl)acrylamide,78)N-(4-fluoro-3-(6-((5-methylthiazole-2-il)amino N)-1-(2,2,2-trifluoroethyl)-1H-pyrolo[3,2-c]pyridin-4-yl)phenyl)acrylamide,79)(S)-1-(3-((1-isopropyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,80)1-(3-((1-isopropyl-6 -((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)acetidin-1-yl)prop-2-n-1-one,81)(S)-1-(3-((1-isobutyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)pyrololidin-1-yl)prop-2-n-1-one,82)(R)-1-(3-((1-isobutyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)pyrolidin-1-yl)prop-2-en-1-one,83)1-((3S,4R)-3-fluoro-4-((1-isopropyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy) Pyrrolidin-1-il)prop-2-n-1-one,84)(S)-1-(3-((1-isopropyl-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)piperidin-1-il)prop-2-n-1-one,85)(S)-1-(2-((1-isobutyl-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c] ]pyridin-4-il)oxy)methyl)pyrrolidin-1-il)prop-2-n-1-one,86)(S)-1-(2-(((1-isopropyl-6-((5-methylthiazole-2-il)amino)-1H-pyrrolo[3,2-c]pyridin-4-il)oxy)methyl)acetidin-1-il)prop-2-n-1-one,87)1-((2R,4S)-4-((1-isopropyl-6-((5-methylthiazole (2S,4S)-4-((1-isopropyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)-2-methylpyrolidin-1-yl)prop-2-N-1-one, 88)1-((2S,4S)-4-((1-isopropyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)-2-methylpyrolidin-1-yl)prop-2-N-1-one,89)(R)-1-(2-(((1-isopropyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)methyl)pyrolidin-1-yl)prop-2-en-1-one,90)(R)-1-(2-(((1-isopropyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)methyl L)acetidin-1-il)prop-2-N-1-one,91)1-((3R,4R)-3-fluoro-4-((1-isopropyl-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)pyrrolidin-1-il)prop-2-N-1-one,92)rac-1-((3S,4R)-3-((1-isopropyl-6-((5-methylthiazole-2-il) Amino)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)-4-methylpyrolidin-1-il)prop-2-n-1-one,93)(R)-1-(4,4-difluoro-2-(((1-isopropyl-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)methyl)pyrolidin-1-il)prop-2-n-1-one ,94)1-((2R,4S)-2-(((1-isopropyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)methyl)-4-methoxypyrolidin-1-yl)prop-2-en-1-one,95)(S)-1-(3-((1-isopropyl-6-((6-(trifluoromethyl)pyrimidin-4-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)pyrrolidin-1-il)prop-2-n-1-one,96)1-((2R,4S)-4-((1-isobutyl-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)-2-methylpyrrolidin-1-il)prop-2-n-1-one,97)(S)-1-(3-((1-(cyclopone (cyclopropylmethyl)-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)pyrolidin-1-yl)prop-2-en-1-one,98)1-((2R,4S)-4-((1-(cyclopropylmethyl)-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)-2- Methylpyrrolidin-1-il)prop-2-n-1-one,99)(S)-1-(3-((1-cyclopentyl-6-((5-methylthiazole-2-il)amino)-1H-pyrrolo[3,2-c]pyridin-4-il)oxy)pyrrolidin-1-il)prop-2-n-1-one,100)1-((2R,4S)-4-((1-cyclopentyl-6-((5-methylthiazole-2- Il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)-2-methylpyrolidin-1-il)prop-2-n-1-one,101)(S)-1-(3-((1-isopropyl-6-((6-methylpyrimidin-4-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)pyrolidin-1-il)prop-2-n-1-one,102)(S)-1-(3-((6-((5-methylthiazole-2-yl)amino)-1-((1-(trifluoromethyl)cyclopropyl)methyl)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)pyrolidin-1-yl)prop-2-en-1-one,103)(S)-1-(3-((1-isopropyl-6-((6-methoxypyrimidin-4-yl)amino)-1H-pyrolo[3,2- c]pyridin-4-il)oxy)pyrrolidin-1-il)prop-2-n-1-one,104)(S)-1-(3-((1-isobutyl-6-((6-methylpyrimidin-4-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)pyrrolidin-1-il)prop-2-n-1-one,105)1-((3S,4R)-3-fluoro-4-((1-isobutyl-6-((5-meth methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)pyrolidin-1-yl)prop-2-en-1-one,106)1-((3R,4R)-3-fluoro-4-((1-isobutyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)pyrolidin-1-yl)prop-2-en-1-one N,107)1-((3R,4S)-3-((1-(cyclopropylmethyl)-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)-4-fluoropyrrolidin-1-yl)prop-2-en-1-one,108)1-((3R,4R)-3-((1-(cyclopropylmethyl)-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)-4-fluoropyrrolidin-1-yl)prop-2-n-1-one,109)1-((3R,4S)-3-((1-cyclopentyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)-4-fluoropyrrolidin-1-yl)prop-2-n-1-one,110)1-((3R,4R)-3-((1-cyclopentyl Pyntil-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)-4-fluoropyrrolidin-1-yl)prop-2-en-1-one,111)1-((S)-3-((1-((S)-secondary-butyl)-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin- 1-il)prop-2-n-1-one,112)1-((3R,4S)-3-((1-((S)-secondary-butyl)-6-((5-methylthiazole-2-il)amino)-1H-pyrrolo[3,2-c]pyridin-4-il)oxy)-4-fluoropyrrolidin-1-il)prop-2-n-1-one,113)1-((3R,4R)-3-((1-((S)-secondary-butyl)-6-((5-methylthiazole (S)-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)-4-fluoropyrrolidin-1-yl)prop-2-n-1-one,114)(S)-1-(3-((1-isopentyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-n-1-one,115)1-((3R,4R)-3-fluoro-4-((1-isopentyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)pyrolidin-1-yl)prop-2-en-1-one,116)1-(3-((1-isobutyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)-4-methylpyrolidin pyridin-1-il)prop-2-en-1-one,117)(S)-1-(3-((6-((5-methylthiazole-2-il)amino)-1-(pyridin-2-ilmethyl)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)pyrolidin-1-il)prop-2-en-1-one,118)1-(3-((1-isobutyl-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c] Pyrrolol[3,2-c]pyridin-4-il)oxy)acetidin-1-il)prop-2-n-1-one,119)1-(3-((1-isobutyl-6-((5-methylthiazole-2-il)amino)-1H-pyrrolo[3,2-c]pyridin-4-il)oxy)-3-methylacetidin-1-il)prop-2-n-1-one,120)1-((3R,4R)-3-fluoro-4-((6-((5-methylthiazole-2-il)amino N)-1-((1-(trifluoromethyl)cyclopropyl)methyl)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)pyrolidin-1-yl)prop-2-N-1-ON,121)(S)-1-(3-((1-benzyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)pyrolidin-1-yl)prop-2-N-1-ON,122)(S)-1-(3-((6-((5-ethylthiazole-2-yl)amino)-1-isobutyl-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)pyrolidin-1-yl)prop-2-en-1-one,123)1-((3S)-3-((1-(2-methylbutyl)-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy )pyrrolidin-1-il)prop-2-en-1-one,124)(S)-1-(3-((1-butyl-6-((5-methylthiazole-2-il)amino)-1H-pyrrolo[3,2-c]pyridin-4-il)oxy)pyrrolidin-1-il)prop-2-en-1-one,125)(S)-1-(3-((1-ethyl-6-((5-methylthiazole-2-il)amino)-1H-pyrrolo[3 [3,2-c]pyridin-4-il)oxy)pyrolidin-1-il)prop-2-en-1-one,126)(S)-1-(3-((6-((5-methylthiazole-2-il)amino)-1-propyl-1H-pyrolo[3,2-c]pyridin-4-il)oxy)pyrolidin-1-il)prop-2-en-1-one,127)(S)-1-(3-((1-(2-methoxyethyl)- ... thazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)pyrolidin-1-il)prop-2-en-1-one,128)(S)-1-(3-((1-(cyclopentylmethyl)-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)pyrolidin-1-il)prop-2-en-1-one,129)(S)-1-(3-((1-(cyclohexylmethyl)-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)pyrolidin-1-yl)prop-2-en-1-one,130)(S)-1-(3-((1-methyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)pyrolo Pyrrolidin-1-il)prop-2-en-1-one,131)1-((3S,4R)-3-fluoro-4-((1-methyl-6-((5-methylthiazole-2-il)amino)-1H-pyrrolo[3,2-c]pyridin-4-il)oxy)pyrrolidin-1-il)prop-2-en-1-one,132)1-((3R,4S)-3-((1-(cyclopentylmethyl)-6-((5-methylthiazole-2-il)am (S)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)-4-fluoropyrrolidin-1-il)prop-2-n-1-one,133)(S)-1-(3-((6-((5-methylthiazole-2-il)amino)-1-((tetrahydro-2H-pyran-4-il)methyl)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)pyrrolidin-1-il)prop-2-n-1 -on,134)1-((3S,4S)-3-fluoro-4-((1-isobutyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-on,135)1-((3R,4S)-3-fluoro-4-((1-isobutyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)pyrolidin-1-il)prop-2-en-1-one,136)1-(6-((1-methyl-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)-1-azaspiro[3.3]heptane-1-il)prop-2-en-1-one,137)1-(6-((1-isobutyl-6-((5-methyl Thiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)-1-azaspiro[3.3]heptane-1-yl)prop-2-en-1-one,138)(S)-1-(3-((6-((5-fluoro-2-methylphenyl)amino)-1-methyl-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)pyrolidin-1-yl)prop-2-en- 1-one,139)1-((3S,4R)-3-fluoro-4-((6-((5-fluoro-2-methylphenyl)amino)-1-methyl-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)pyrolidin-1-yl)prop-2-en-1-one,140)(S)-1-(3-((1-(2-hydroxy-2-methylpropyl)-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)pyrololidin ... Pyrolo[3,2-c]pyridin-4-il)oxy)pyrrolidin-1-il)prop-2-n-1-one,141)1-((3S,4R)-3-fluoro-4-((1-(2-hydroxy-2-methylpropyl)-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)pyrrolidin-1-il)prop-2-n-1-one,142)1-(3-((1-cyclopentyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)acetidin-1-yl)prop-2-en-1-one,143)(R)-1-(3-((1-cyclopentyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)pyrolidin-1- yl)prop-2-n-1-one,144)(R)-1-(3-((1-(cyclopropylmethyl)-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-n-1-one,145)1-(3-((1-(cyclopropylmethyl)-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3, 2-c]pyridin-4-yl)oxy)acetidin-1-yl)prop-2-n-1-one,146)1-(3-((1-(2-methoxyethyl)-6-((5-methylthiazole-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)acetidin-1-yl)prop-2-n-1-one,147)1-((3S,4R)-3-fluoro-4-((1-(2-methoxyethyl)-6-( (5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)pyrolidin-1-yl)prop-2-n-1-one,148)(S)-1-(3-((1-(2-methoxyethyl)-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)piperidin-1-yl)prop-2-n-1-one,149)(S)-1-(3-((1-(cyclopropylmethyl)-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)piperidin-1-yl)prop-2-en-1-one,150)(S)-1-(3-((1-isobutyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy )Piperidin-1-il)prop-2-en-1-one,151)(S)-1-(3-((1-cyclopentyl-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)piperidin-1-il)prop-2-en-1-one,152)1-((3R,4S)-3-((1-ethyl-6-((5-methylthiazole-2-il)amino)-1H-pyrolo Lo[3,2-c]pyridin-4-il)oxy)-4-fluoropyrrolidin-1-il)prop-2-n-1-one,153)(S)-1-(3-((1-ethyl-6-((5-methylthiazole-2-il)amino)-1H-pyrrolo[3,2-c]pyridin-4-il)oxy)piperidin-1-il)prop-2-n-1-one,154)1-((3R,4R)-3-((1-ethyl-6-((5-methylthiazole-2-il)amino)-1H-pyrrolo[3,2-c]pyridin-4-il)oxy)piperidin-1-il)prop-2-n-1-one,154)1-((3R,4R)-3-((1-ethyl-6-((5-methylthiazole-2-il)amino)-1H methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)-4-fluoropyrrolidin-1-yl)prop-2-n-1-one,155)1-(3-((1-ethyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)-3-methylacetidin-1-yl)prop-2-n-1-one,156)(R)-1-(3-((1-methyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)pyrolidin-1-yl)prop-2-en-1-one,157)1-((3R,4R)-3-fluoro-4-((1-methyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy) Prolidin-1-il)prop-2-en-1-one,158)(S)-1-(3-((1-methyl-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)piperidin-1-il)prop-2-en-1-one,159)1-((3S,4R)-3-fluoro-4-((6-((5-methylthiazole-2-il)amino)-1-propyl ... Pyrolo[3,2-c]pyridin-4-il)oxy)pyrrolidin-1-il)prop-2-en-1-one,160)(S)-1-(3-((6-((5-methylthiazole-2-il)amino)-1-propyl-1H-pyrrolo[3,2-c]pyridin-4-il)oxy)piperidin-1-il)prop-2-en-1-one,161)1-((3R,4R)-3-fluoro-4-((6-((5-methyl Thiazole-2-il)amino)-1-propyl-1H-pyrolo[3,2-c]pyridin-4-il)oxy)pyrolidin-1-il)prop-2-en-1-one,162)(R)-1-(3-((1-isopropyl-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)pyrolidin-1-il)prop-2-en-1-one,163)1-(3-((1-isopropyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)-3-methylacetidin-1-yl)prop-2-en-1-one,164)1-((2S,4S)-4-((1-cyclopentyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)-2-methyl Pyrrolidin-1-il)prop-2-en-1-one,165)1-(3-((1-cyclopentyl-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)-3-methylacetidin-1-il)prop-2-en-1-one,166)1-(3-methyl-3-((1-methyl-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2 -c]pyridin-4-il)oxy)acetidin-1-il)prop-2-n-1-one,167)1-(3-((1-(cyclopropylmethyl)-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)-3-methylacetidin-1-il)prop-2-n-1-one,168)1-(3-((1-(2-methoxyethyl)-6-((5-methylthiazole L-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)-3-methylacetidin-1-il)prop-2-en-1-one,169)(S)-1-(3-((1-(cyclopentylmethyl)-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)piperidin-1-il)prop-2-en-1-one,170)1-((3R,4R)-3-((1-(cyclopentylmethyl)-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)-4-fluoropyrrolidin-1-yl)prop-2-en-1-one,171)1-((3S,4R)-3-fluoro-4-((1-(2-methylbutyl)-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin Ridin-4-il)oxy)pyrrolidin-1-il)prop-2-en-1-one,172)1-((3S)-3-((1-(2-methylbutyl)-6-((5-methylthiazole-2-il)amino)-1H-pyrrolo[3,2-c]pyridin-4-il)oxy)piperidin-1-il)prop-2-en-1-one,173)1-((3R,4R)-3-fluoro-4-((1-(2-methylbutyl)-6-((5 -methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)pyrolidin-1-yl)prop-2-en-1-one,174)1-((3R,4R)-3-fluoro-4-((1-((R)-2-methylbutyl)-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)pyrolidin-1-yl)prop ์-2-N-1-ONE,175)1-((3R,4R)-3-fluoro-4-((1-((S)-2-methylbutyl)-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)pyrolidin-1-yl)prop-2-N-1-ONE,176)1-(3-methyl-3-((6-((5-methylthiazole-2-yl)amino)-1-propyl-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)acetidin-1-yl)prop-2-en-1-one,177)1-(3-((1-isopentyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)-3-methylacetidin-1-yl)prop-2-en-1-one,178)1-(3-((1-(cyclopentylmethyl)-6-((5- Methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)-3-methylacetidin-1-yl)prop-2-en-1-one,179)1-((2S,4S)-4-((1-isobutyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)-2-methylpyrrolidin-1-yl )prop-2-n-1-one,180)1-((2S,4S)-4-((1-(cyclopropylmethyl)-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)-2-methylpyrrolidin-1-yl)prop-2-n-1-one,181)2-((4-((3R,4S)-1-acryloyl-4-fluoropyrrolidin-3-yl) Oxy)-1-isobutyl-1H-pyrolo[3,2-c]pyridin-6-yl)amino)thiazole-5-carbonitrile,182)2-((4-(((3R,4S)-1-acryloyl-4-fluoropyrrolidin-3-yl)oxy)-1-isobutyl-1H-pyrolo[3,2-c]pyridin-6-yl)amino)-N-methylthiazole-5-carboxamide,183)(S)-1-(3-((1-isopropyl-6-((4-methoxypyrimidin-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,184)(S)-1-(3-((1-isopropyl-6-((3-methoxypyrazin-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one 1-((2S,4S)-2-methyl-4-((1-methyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,186)1-((2S,4S)-4-((1-ethyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrrolo[3,2-c]pyridin Pyridin-4-il)oxy)-2-methylpyrrolidin-1-il)prop-2-n-1-one,187)1-((2S,4S)-2-methyl-4-((6-((5-methylthiazole-2-il)amino)-1-propyl-1H-pyrrolo[3,2-c]pyridin-4-il)oxy)pyrrolidin-1-il)prop-2-n-1-one,188)(S)-1-(3-((1-(2-fluoroethyl)-6-((5-methylthiazole-2-il)amino)-1-propyl-1H-pyrrolo[3,2-c]pyridin-4-il)oxy)pyrrolidin-1-il)prop-2-n-1-one,188)(S)-1-(3-((1-(2-fluoroethyl)-6-((5-methylthiazole-1 ... thazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)pyrolidin-1-yl)prop-2-en-1-one,189)1-((3S,4R)-3-fluoro-4-((1-(2-fluoroethyl)-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)pyrolidin-1-yl)prop-2-en-1-one,190)(S)-1-(3-((1-(3-fluoropropyl)-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)pyrolidin-1-yl)prop-2-en-1-one,191)1-((3S,4R)-3-fluoro-4-((1-(3-fluoropropyl)-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[ [3,2-c]pyridin-4-yl)oxy)pyrolidin-1-yl)prop-2-n-1-one,192)(S)-1-(3-((6-((1H-pyrazole-3-yl)amino)-1-isopropyl-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)pyrolidin-1-yl)prop-2-n-1-one,193)(S)-1-(3-((1-isopropyl-6-((1-methyl-1H- Pyrazole-3-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)pyrolidin-1-il)prop-2-en-1-one,194)(S)-1-(3-((1-isopropyl-6-((5-methyl-1H-pyrazole-3-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)pyrolidin-1-il)prop-2-en-1-one,1 95)1-((3R,4S)-3-((6-((1H-pyrazole-3-il)amino)-1-isobutyl-1H-pyrolo[3,2-c]pyridin-4-il)oxy)-4-fluoropyrrolidin-1-il)prop-2-en-1-one,196)1-((3S,4R)-3-fluoro-4-((1-isobutyl-6-((5-methyl-1H-pyrazole-3-il)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,197)1-((3S,4R)-3-fluoro-4-((1-isobutyl-6-((1-methyl-1H-pyrazole-3-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one,198)(S)-3-((4-((1-acryloylpyrrol Lidin-3-yl)oxy)-1-isopropyl-1H-pyrolo[3,2-c]pyridin-6-yl)amino)-1-methylpyridin-2(1H)-one,199)3-((4-((3R,4S)-1-acryloyl-4-fluoropyrolidin-3-yl)oxy)-1-isobutyl-1H-pyrolo[3,2-c]pyridin-6-yl)amino)-1-methylpyridin-2(1H)-one,200)1 -(2-((1-isobutyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)-5-azaspiro[3.4]octane-5-yl)prop-2-en-1-one,201)1-(7-((1-isobutyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)-1-azaspiro[4 .4]nonen-1-il)prop-2-en-1-one,202)1-(2-((1-isobutyl-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)-6-azaspiro[3.4]octen-6-il)prop-2-en-1-one,203)1-(2-((1-isobutyl-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)-5-azaspiro[3.5]nonen-5-il)prop-2-en-1-one,204)1-(7-((1-isobutyl-6-((5-methylthiazole-2-il)amino)-1H-pyrrolo[3,2-c]pyridin-4-il)oxy)-2-azaspiro[4.4]nonen-2-il)prop-2-en-1-one,205)(S)-1-(3-((6-((5-methylthiazole -2-yl)amino)-1-(2,2,2-trifluoroethyl)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)pyrolidin-1-yl)prop-2-en-1-one,206)(S)-1-(3-((1-(2,2-difluoroethyl)-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)pyrolidin-1-yl)prop 2-N-1-ONE,207)(R)-1-(2-(((6-((5-methylthiazole-2-yl)amino)-1-(2,2,2-trifluoroethyl)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)methyl)pyrolidin-1-yl)prop-2-N-1-ONE,208)(R)-1-(2-((6-((5-methylthiazole-2-yl)amino)-1-(2,2,2-trifluoroethyl)-1H -pyrolo[3,2-c]pyridin-4-il)oxy)methyl)acetidin-1-il)prop-2-n-1-one,209)(R)-1-(2-(((1-(2,2-difluoroethyl)-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)methyl)acetidin-1-il)prop-2-n-1-one,210)(R)-1-(2-(((1-(2,2-difluoroethyl)-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)methyl)pyrolidin-1-yl)prop-2-en-1-one,211)1-((3S,4R)-3-fluoro-4-((6-((5-methylthiazole-2-yl)amino)-1-(2,2,2-trifluoroethyl)-1H-pyrolo[3,2-c]pyridin 1-4-il)oxy)pyrolidin-1-il)prop-2-n-1-one,212)1-((2R,4S)-2-methyl-4-((6-((5-methylthiazole-2-il)amino)-1-(2,2,2-trifluoroethyl)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)pyrolidin-1-il)prop-2-n-1-one,213)1-((S)-3-((6-((5-methylthiazole L-2-il)amino)-1-((R)-1,1,1-trifluoropropane-2-il)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)pyrolidin-1-il)prop-2-en-1-one,214)(R)-1-(3-(((1-isobutyl-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)methyl)piperidi N-1-il)prop-2-N-1-one,215)(S)-1-(3-(((1-isobutyl-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)methyl)piperidin-1-il)prop-2-N-1-one,216)(S)-1-(3-(((1-isobutyl-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)methyl)pyrolidin-1-il)prop-2-n-1-one,217)1-(2-(((1-cyclopentyl-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)methyl)pyrolidin-1-il)prop-2-n-1-one,218)1-(2-(((1-cyclopentyl- 6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)methyl)acetidin-1-yl)prop-2-en-1-one,219)(S)-1-(2-((1-isopropyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)methyl)pyrolidin-1- yl)prop-2-n-1-one,220)(S)-1-(2-(((1-(cyclopentylmethyl)-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)methyl)pyrrolidin-1-yl)prop-2-n-1-one,221)1-((2S)-2-(((1-(2-methylbutyl)-6-((5-methylthiazole-2-yl) )amino)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)methyl)pyrolidin-1-il)prop-2-en-1-one,222)(S)-1-(2-(((1-cyclopentyl-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)methyl)pyrolidin-1-il)prop-2-en-1-one,223)(R)-1-(2-(((1-cyclopentyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)methyl)acetidin-1-yl)prop-2-en-1-one,224)(S)-2-fluoro-1-(3-((1-isobutyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin -4-il)oxy)pyrolidin-1-il)prop-2-en-1-one,225)(S)-1-(3-((1-isobutyl-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)pyrolidin-1-il)prop-2-en-1-one,226)(S,E ... L)amino)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)pyrolidin-1-il)but-2-en-1-one,227)(S,E)-4-(dimethylamino)-1-(3-((1-isobutyl-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)pyrolidin-1-il)but-2-en-1-one ,228)N-(4-(((3R,4S)-4-fluoro-1-(vinylsulfonyl)pyrrolidin-3-yl)oxy)-1-isobutyl-1H-pyrroloh[3,2-c]pyridin-6-yl)-5-methylthiazole-2-amine,229)2-chloro-1-((3S,4R)-3-fluoro-4-((1-isobutyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrroloh[3,2-c]pyridin-4-il)oxy)pyrolidin-1-il)ethane-1-one,230)1-((3S,4R)-3-fluoro-4-((1-isobutyl-6-((5-methylthiazole-2-il)amino)-1H-pyrolo[3,2-c]pyridin-4-il)oxy)pyrolidin-1-il)but-2-ine- 1-Oene and 231)1-((3S,4R)-3-fluoro-4-((1-isobutyl-6-((5-methylthiazole-2-yl)amino)-1H-pyrolo[3,2-c]pyridin-4-yl)oxy)pyrrolidin-1-yl)prop-2-ine-1-Oene 14. A pharmaceutical composition which contains any one of the compounds claimed under claims 1 to 13 or a pharmaceutically acceptable salt of such compounds as the active ingredient.

15. A pharmaceutical composition for the prevention or treatment of a disease caused by inflammation, autoimmune disease or cancer which contains any one of the compounds claimed under claims 1 to 13 or a pharmaceutically acceptable salt of such compounds as the active ingredient;