FGFR inhibitors and methods of use thereof

Abstract

Provided are novel compounds of formula (I) and pharmaceutical compositions, pharma- ceutically acceptable salts, prodrugs, solvates, hydrates, tautomers, and isomers thereof, useful as FGFR inhibitors for regulating or inhibiting the activity of FGFR enzymes, as well as methods of treating disorders associated with FGFR signaling using the compounds and compositions, including but not limited to those described herein. TIFF2024536858000204.tif31170

Description

[Technical field]

[0001] The present invention relates to certain novel fused heterocyclic derivative compounds of formula I, II, III, IV, V, VI, VII, II, or I-II as FGFR inhibitors, as well as their salts and pharmaceutical compositions.Use for treating FGFR-mediated disorders and cancers, as well as methods for inhibiting FGFR activity and treating FGFR-related disorders and cancers, and methods for preparing the compounds of formula I, II, III, IV, V, VI, VII, II, or I-II are also described.More specifically, the present invention is directed to fused heterocyclic derivatives useful as inhibitors of FGFR, methods for preparing such compounds, and methods for treating FGFR-mediated disorders. [Background technology]

[0002] Fibroblast growth factor receptors (FGFR1, FGFR2, FGFR3, and FGFR4) are receptor tyrosine kinases consisting of an extracellular ligand-binding domain and an intracellular tyrosine kinase domain. Binding of FGF ligands leads to receptor dimerization and conformational changes in the intracellular domain, resulting in intermolecular transphosphorylation of the kinase domain and intracellular tail. The phosphorylated residues serve as docking sites for adaptor proteins that promote downstream signaling cascades that lead to cellular behaviors including proliferation, survival, differentiation, migration, and angiogenesis. Deregulated FGFR signaling can occur through FGFR gene amplification or fusions, FGFR missense mutations, receptor overexpression resulting from dysregulation of epigenetic and / or transcriptional regulators, or upregulation of FGF ligands in the tumor microenvironment. FGFRs are expressed in many cell types. Thus, aberrant FGFR signaling is involved in tumorigenesis, tumor progression, and resistance to therapy across many tumor types (for a review of FGFR signaling, see N. Turner and R. Grose, Nat. Rev. Cancer 2010, 10:116-129, and references cited therein).

[0003] Pan-FGFR1-3 inhibitors have produced clinical responses in a number of FGFR-altered cancers, but on-target toxicity limits the administration of these inhibitors. One of the most common adverse effects of pan-FGFR inhibition is hyperphosphatemia. Regulation of phosphate reabsorption is mediated by FGFR1. Thus, FGFR-selective inhibitors that spare FGFR1 are needed (J. Gattineni et al., Am. J Physiol. Renal Physiol 2014, 306:F351-F358; X. Han et al., PLoS One 2016, ll:e0147845). Cancers with FGFR2 gene fusions and cancers with FGFR2 amplifications and / or FGFR2 activating mutations have shown responses to pan-FGFR inhibition, but the low rate and short duration of responses suggest that they were limited by toxicity. Thus, there is a need for FGFR2 selective inhibitor compounds and methods of using these compounds to treat cancer and other disorders (for reviews of pan-FGFR1-3 inhibitors and clinical responses, see IS. Babina and N. C. Turner, Nat. Rev. Cancer 2017, 17:318-332; M. Katoh, Nat. Rev. Clin Oneal. 2019, 16:105-122; and references cited therein). [Prior art documents] [Non-patent literature]

[0004] [Non-Patent Document 1] N. Turner and R. Grose, Nat. Rev. Cancer 2010, 10:116-129 [Non-Patent Document 2] J. Gattineni et al., Am.J Physiol.Renal Physiol 2014, 306:F351-F358 [Non-Patent Document 3] X. Han et al., PLoS One 2016, ll:e0147845 [Non-Patent Document 4] IS Babina and N.C. Turner, Nat. Rev. Cancer 2017, 17:318-332 [Non-Patent Document 5] M. Katoh, Nat. Rev. Clin Oneal. 2019, 16:105-122 Summary of the Invention [Problem to be solved by the invention]

[0005] The present invention provides compounds of formula (I), as well as pharmaceutical compositions, pharma- ceutically acceptable salts, prodrugs, solvates, hydrates, tautomers, and isomers thereof, that are useful as inhibitors of FGFR2. [Means for solving the problem]

[0006] The present invention relates to a compound represented by formula (I) [ka] or pharma- ceutically acceptable salts, prodrugs, solvates, hydrates, tautomers, and isomers thereof, Ring A is [ka] is selected from [ka] represents a bond to ring D, [ka] represents a bond to ring B, R a Each of is independently H, D, CN, NH2, OH, halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxyl, -(CH2) 0~2 -NHR', -(CH2) 0~2N(R')2, or a 3-6 membered saturated heterocyclic ring having 1 or 2 heteroatoms which may be independently selected from N, O or S, each of which is independently unsubstituted or contains 1, 2 or 3 instances of D, OH, halogen, C 1~3 Alkyl or C 1~3 may be substituted with alkoxy; R a ', D, CN, OH, C 1~6 alkoxyl, -CONH2, -COR', -CONHR', or -CON(R')2, each of which is independently unsubstituted or contains 1, 2, or 3 instances of D, OH, halogen, C 1~3 Alkyl or C 1~3 may be substituted with alkoxy; or R a and R a ' together with their intervening atoms form a 5- to 7-membered heterocyclic ring having at least one nitrogen atom, each of which is independently unsubstituted or contains 1, 2, 3, or 4, or 1~3 Alkoxy, C 1~3 optionally substituted with alkyl, D or halogen; Ring B is phenylene; a divalent saturated or partially unsaturated 3- to 10-membered carbocyclic ring; independently N, O, S, S(O), S(O)2, S(O)(NH), or S(O)(NC 1~3 a divalent saturated or partially unsaturated 3- to 10-membered heterocyclic ring having 1 to 5 heteroatoms selected from -N, -O, or -S; or a 5- to 10-membered heteroarylene having 1 to 5 heteroatoms or groups independently selected from -N, -O, or -S, each of which is independently unsubstituted or -L b -R b In addition to r example R B and r is 0, 1, 2, 3 or 4; Ring D is phenylene; a divalent saturated or partially unsaturated 3- to 10-membered carbocyclic ring; independently N, O, S, S(O), S(O)2, S(O)(NH), or S(O)(NC 1~3a divalent saturated or partially unsaturated 3- to 10-membered heterocyclic ring having 1 to 5 heteroatoms selected from -N, -O, or -S; or a 5- to 10-membered heteroarylene having 1 to 5 heteroatoms independently selected from -N, -O, or -S, each of which is independently unsubstituted or -L d -R d In addition to the example of R D and u is 0, 1, 2, 3 or 4; R B or R D each independently represents -D, oxo, -OH, -NH2, -CN, -NO2, -(CH2) 0~2 NHR', -(CH2) 0~2 N(R')2, -(CH2) 0~2 may be selected from -OR', R, -SO2R, or -COR; L b and L d Each of is independently a covalent bond, -O-, -S-, -NHS(O)2-, -S(O)-, S(O)2-, -CO-, -NH-, -(CH2) 1~3 , -CONH-, -NHCO-, -CONH(CH2) 1~3 -, -NHCO(CH2) 1~3 -, or -NHCONH-, each CH2 is independently unsubstituted or selected from 1, 2 or 3 instances of D, halogen, C 1~3 Alkyl or C 1~3 each NH is independently unsubstituted or substituted with C 1~3 may be substituted with alkyl; R b is halogen, CN, [ka] and R b1 , R b2 , and R b3 each independently represents H, D, halogen, -CN, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 2~6 Alkenyl, C 2~6Alkynyl, -(CH2) 0~2 NHR', -(CH2) 0~2 N(R')2 or -(CH2) 0~2 OR′, each of which may be independently unsubstituted or substituted with 1, 2, 3 instances of halogen or D; or R b1 and R b2 , R b2 and R b3 , R b1 and L b form, together with the intervening atoms, a 4-7 membered saturated or partially unsaturated ring having 0-2 heteroatoms or groups selected from N, O, S, S(O), or S(O)2; R d is H;D;C 1~6 alkyl; phenyl; a saturated or partially unsaturated 3-10 membered carbocyclic ring; a saturated or partially unsaturated 3-10 membered heterocyclic ring having 1-5 heteroatoms independently selected from N, O, S, S(O), or S(O)2; or a 5-10 membered heteroaryl having 1-5 heteroatoms or groups independently selected from N, O, or S, each of which may be independently unsubstituted or substituted with 1, 2, 3 instances of R; Each R is independently halogen, -CN, -C 1~6 Alkyl, -C 3~6 Cycloalkyl, -SC 1~6 Alkyl, -N(C 1~6 Alkyl)2, -NHC 1~6 Alkyl, -NHC 3~6 Cycloalkyl, -C 1~6 Alkoxy or -OC 3~6 cycloalkyl, each of which may be unsubstituted or substituted with 1, 2, 3 instances of D or halogen; Each R' is independently C 1~6 Alkyl or C 3~6 cycloalkyl; or Two R's, together with the nitrogen to which they are both attached, form a 4-6 membered heterocyclic ring, which may have one or two additional heteroatoms or groups selected from N, O, S, S(O), or S(O)2. Provided are compounds, or pharma- ceutically acceptable salts, prodrugs, solvates, hydrates, tautomers, and isomers thereof.

[0007] In some embodiments, the present invention provides compounds of formula (I) represented by formula (II): [ka]

[0008] In some embodiments, the present invention provides compounds of formula (I) represented by formula (III): [ka]

[0009] In some embodiments, the present invention provides compounds of formula (I) represented by formula (IV): [ka]

[0010] In some embodiments, the present invention provides compounds of formula (I) represented by formula (V): [ka]

[0011] In some embodiments, the present invention provides compounds of formula (I) represented by formula (VI): [ka]

[0012] In some embodiments, the present invention provides compounds of formula (I) represented by formula (VII): [ka]

[0013] In some embodiments of formula (I) provided by the present invention, R a each independently represents H, D, CN, NH2, OH, F, Cl, Br, C 1~3 Alkyl, C 1~3 alkoxyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, -NHR', -CHNHR', -(CH)NHR', -N(R'), -CHN(R'), -(CH)N(R'), a 3-membered saturated heterocyclic ring, a 4-membered saturated heterocyclic ring, a 5-membered saturated heterocyclic ring, or a 6-membered saturated heterocyclic ring, further wherein each of the heterocyclic rings has 1 or 2 heteroatoms which may be independently selected from N, O, or S, each of which may be independently unsubstituted or substituted with 1, 2, or 3 instances of D, OH, F, Cl, Br, methyl, ethyl, propyl, methoxy, or ethoxy.

[0014] In some embodiments of formula (I) provided by the present invention, R a each may be independently selected from H, D, CN, NH, OH, F, Cl, methyl, ethyl, propyl, iso-propyl, methoxy, ethoxy, propoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, -NHR', -CHNHR', -(CH)NHR', -N(R'), -CHN(R'), -(CH)N(R'), a 4-membered saturated heterocyclic ring, a 5-membered saturated heterocyclic ring, or a 6-membered saturated heterocyclic ring, further each of the saturated heterocyclic rings having 1 or 2 heteroatoms which may be independently selected from N or O, each of which may be independently unsubstituted or substituted with 1, 2 or 3 instances of D, OH, F, Cl, methyl, ethyl, methoxy, or ethoxy.

[0015] In some embodiments of formula (I) provided by the present invention, R aare independently selected from H, D, CN, NH, OH, F, methyl, cyclopropyl, cyclobutyl, -NHR', -CHNHR', -(CH)NHR', -N(R'), -CHN(R'), -(CH)N(R'), a 4-membered saturated heterocyclic ring, a 5-membered saturated heterocyclic ring, or a 6-membered saturated heterocyclic ring, further each of the heterocyclic rings having 1 or 2 heteroatoms which may be independently selected from N, or O, each of which may be independently unsubstituted or substituted with 1, 2 or 3 instances of D, OH, or F.

[0016] In some embodiments of formula (I) provided by the present invention, R a Each of [ka] It is.

[0017] In some embodiments of formula (I) provided by the present invention, R a ', D, CN, OH, C 1~3 alkoxyl, -CONH2, -COR', -CONHR', or -CON(R')2, each of which may be independently unsubstituted or substituted with 1, 2 or 3 instances of D, OH, F, Cl, Br, methyl, ethyl, propyl, iso-propyl, methoxy, ethoxy, or propoxy.

[0018] In some embodiments of formula (I) provided by the present invention, R a ' is D, CN, OH, methoxy, ethoxy, propoxy, -CONH2, -COR', -CONHR', or -CON(R')2, each of which may be independently unsubstituted or substituted with 1, 2 or 3 instances of D, OH, F, Cl, methyl, ethyl, methoxy, or ethoxy.

[0019] In some embodiments of formula (I) provided by the present invention, R a ' is D, CN, or -CONH2.

[0020] In some embodiments of formula (I) provided by the present invention, R a and R a ' together with their intervening atoms form a 5-membered heterocyclic ring, a 6-membered heterocyclic ring, or a 7-membered heterocyclic ring, and further, each of the heterocyclic rings may also contain one additional heteroatom selected from N or S, each of which may independently be unsubstituted or substituted with 1, 2, 3 instances of methyl, ethyl, methoxy, ethoxy, D, F, or Cl.

[0021] In some embodiments of formula (I) provided by the present invention, R a and R a ' together with their intervening atoms form a 6-membered heterocyclic ring having one N atom or one N atom and one O atom, each of which may be independently unsubstituted or substituted with 1, 2, 3 instances of methyl, D, F, or Cl.

[0022] In some embodiments of formula (I) provided by the present invention, B is phenylene; a divalent saturated or partially unsaturated 5-9 membered carbocyclic ring; a divalent saturated or partially unsaturated 5-9 membered heterocyclic ring having 1-4 heteroatoms independently selected from N, O, S, S(O), or S(O)2; or a 5-9 membered heteroarylene having 1-4 heteroatoms independently selected from N, O, or S, each of which is independently unsubstituted or selected from -L. b -R b In addition to r example R B may be substituted with.

[0023] In some embodiments of formula (I) provided by the present invention, ring B is phenylene; a divalent saturated or partially unsaturated 5-, 6-, 7-, 8-, or 9-membered carbocyclic ring; a divalent saturated or partially unsaturated 5-, 6-, 7-, 8-, or 9-membered heterocyclic ring having 1, 2, 3, or 4 heteroatoms independently selected from N, O, or S; or a 5-, 6-, 7-, 8-, or 9-membered heteroarylene having 1, 2, 3, or 4 heteroatoms independently selected from N, O, or S, each of which is independently unsubstituted or -L. b -R b In addition to r example R B may be substituted with.

[0024] In some embodiments of formula (I) provided by the present invention, ring B is phenylene; a divalent saturated 5-, 6-, or 7-membered heterocyclic ring having 1, 2, or 3 heteroatoms independently selected from N or O; or a 5-, 6-, or 7-membered heteroarylene having 1, 2, or 31, or 2 heteroatoms independently selected from N or O, each of which is independently unsubstituted or -L. b -R b In addition to r example R B may be substituted with.

[0025] In some embodiments of formula (I) provided by the present invention, ring B is phenylene; a divalent saturated 5- or 6-membered heterocyclic ring having 1 or 2 heteroatoms independently selected from N; or a 5- or 6-membered heteroarylene having 1 or 2 heteroatoms independently selected from N, each of which is independently unsubstituted or selected from -L. b -R b In addition to r example R B may be substituted with.

[0026] In some embodiments of formula (I) provided by the present invention, ring B is phenylene, [ka] and [ka] Each of the optionally selected rings A or -L b -R b each of which is independently unsubstituted or -L b -R b In addition to r example R B may be substituted with.

[0027] In some embodiments of formula (I) provided by the present invention, ring D is phenylene; a divalent saturated or partially unsaturated 5-9 membered carbocyclic ring; a divalent saturated or partially unsaturated 5-9 membered heterocyclic ring having 1-4 heteroatoms independently selected from N, O, S, S(O), or S(O)2; or a 5-9 membered heteroarylene having 1-4 heteroatoms independently selected from N, O, or S, each of which is independently unsubstituted or selected from -L. d -R d In addition to the example of R D may be substituted with.

[0028] In some embodiments of formula (I) provided by the present invention, ring D is phenylene; a divalent saturated or partially unsaturated 5-, 6-, 7-, 8-, or 9-membered carbocyclic ring; a divalent saturated or partially unsaturated 5-, 6-, 7-, 8-, or 9-membered heterocyclic ring having 1, 2, 3, or 4 heteroatoms independently selected from N, O, or S; or a 5-, 6-, 7-, 8-, or 9-membered heteroarylene having 1, 2, 3, or 4 heteroatoms independently selected from N, O, or S, each of which is independently unsubstituted or -L. d -R d In addition to the example of R D may be substituted with.

[0029] In some embodiments of formula (I) provided by the present invention, ring D is phenylene; a divalent saturated 5-, 6-, or 7-membered heterocyclic ring having 1, 2, or 3 heteroatoms independently selected from N or O; or a 5-, 6-, or 7-membered heteroarylene having 1, 2, or 31, or 2 heteroatoms independently selected from N or O, each of which is independently unsubstituted or -L. d -R d In addition to the example of R D may be substituted with.

[0030] In some embodiments of formula (I) provided by the present invention, ring D is phenylene; a divalent saturated 5- or 6-membered heterocyclic ring having 1 or 2 heteroatoms independently selected from N; or a 5- or 6-membered heteroarylene having 1 or 2 heteroatoms independently selected from N, each of which is independently unsubstituted or -L. d -R d In addition to the example of R D may be substituted with.

[0031] In some embodiments of formula (I) provided by the present invention, each ring D is phenylene; [ka] It is.

[0032] In some embodiments of formula (I) provided by the present invention, R B or R D each may be independently selected from -D, oxo, -OH, -NH2, -CN, -NO2, -NHR', -CH2NHR', -(CH2)2NHR', -N(R'), -CH2N(R'), -(CH2)2N(R'), -OR', -CH2OR', -(CH2)2OR', R, -SO2R, or -COR.

[0033] In some embodiments of formula (I) provided by the present invention, R B or R Deach may be independently selected from -D, oxo, -OH, -NH2, -CN, -NO2, R, -NHR', -CH2NHR', -(CH2)2NHR', -N(R')2, -CH2N(R')2, or -(CH2)2N(R')2.

[0034] In some embodiments of formula (I) provided by the present invention, R B each of which is independently [ka] It is.

[0035] In some embodiments of formula (I) provided by the present invention, R D each independently represents H, D, F, Cl, CN, OH, methyl, ethyl, propyl, cyclopropyl, -SMe, -OMe, -OEt, -CFH2, -CF2H 、 -CF3, each of which may be independently unsubstituted or substituted with 1, 2 or 3 instances of F, Cl, or D.

[0036] In some embodiments of formula (I) provided by the present invention, L b and L d may be independently selected from a covalent bond, -O-, -S-, -CO-, -NH-, -CH2-, -(CH2)2, -CONH-, -NHCO-, -CONHCH2-, -CONH(CH2)2-, -NHCO(CH2)2-, -NHCOCH2-, or -NHCONH-, each of which is independently unsubstituted or selected from any one of R L may be substituted with.

[0037] In some embodiments of formula (I) provided by the present invention, L b and L deach may be independently selected from a covalent bond, -O-, -S-, -CO-, -NH-, -CONH-, -NHCO-, each of which may be independently unsubstituted or substituted with 1, 2 or 3 instances of D, F, Cl, Br, methyl, ethyl, propyl, methoxy, ethoxy, propoxy, methyl substituted with F or Cl, ethyl substituted with F or Cl, propyl substituted with F or Cl, methoxy substituted with F or Cl, ethoxy substituted with F or Cl, or propoxy substituted with F or Cl.

[0038] In some embodiments of formula (I) provided by the present invention, L b and L d each may be independently selected from a covalent bond, -O-, -S-, -CO-, -NH-, -CONH-, -NHCO-, each of which may be independently unsubstituted or substituted with 1, 2 or 3 instances of D, F, Cl, methyl, methoxy, methyl substituted with F or Cl, or methoxy substituted with F or Cl.

[0039] In some embodiments of formula (I) provided by the present invention, R b is halogen, CN, [ka] It is.

[0040] In some embodiments of formula (I) provided by the present invention, R b teeth, [ka] It is.

[0041] In some embodiments of formula (I) provided by the present invention, R b1 , R b2 , and R b3 each independently represents H, D, F, Cl, Br, -CN, C 1~3 Alkyl, C 3~6Cycloalkyl, C 2~3 Alkenyl, C 2~6 alkynyl, -CH2NHR', -(CH2)2NHR', -CH2N(R')2, -(CH2)2N(R')2, -OCR'-CH2OCR', or -(CH2)2OCR', each of which may be independently unsubstituted or substituted with 1, 2, 3 instances of F, Cl, Br, or D.

[0042] In some embodiments of formula (I) provided by the present invention, R b1 , R b2 , and R b3 may each be independently selected from H, D, F, Cl, -CN, methyl, ethyl, propyl, i-propylvinyl, ethynyl, or ethynyl, each of which may be independently unsubstituted or substituted with 1, 2, 3 instances of F, Cl, or D.

[0043] In some embodiments of formula (I) provided by the present invention, R b1 , R b2 , and R b3 Each of may be independently selected from H, D, F, Cl, -CN, or methyl, each of which may be independently unsubstituted or substituted with 1, 2, 3 instances of F or D.

[0044] In some embodiments of formula (I) provided by the present invention, R d is H;D;C 1~3alkyl; phenyl; a 3-, 4-, 5-, 6-, or 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5-, 6-, 7-, 8-, or 9-membered saturated or partially unsaturated bicyclic carbocyclic ring; a 5- or 6-membered monocyclic heteroaryl ring having 1 or 2 heteroatoms independently selected from N, O, or S; a 3-, 4-, 5-, 6-, or 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 or 2 heteroatoms independently selected from N, O, or S; or a 5-, 6-, 7-, 8-, or 9-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 or 2 heteroatoms independently selected from N, O, or S, each of which may be independently unsubstituted or substituted by 1, 2, 3 instances of R.

[0045] In some embodiments of formula (I) provided by the present invention, R d is H; D; methyl; ethyl; propyl; i-propyl; phenyl; a 5- or 6-membered monocyclic heteroaryl ring having 1 or 2 heteroatoms independently selected from N or S; a 3-, 4-, 5-, 6-, or 7-membered saturated monocyclic carbocyclic ring; a 4-, 5-, or 6-membered saturated monocyclic heterocyclic ring having 1 or 2 heteroatoms independently selected from N, O, or S; or a 5-, 6-, or 7-membered saturated bicyclic carbocyclic ring, each of which may be independently unsubstituted or substituted by 1, 2, or 3 instances of R.

[0046] In some embodiments of formula (I) provided by the present invention, R d is H; D; methyl; ethyl; phenyl; a 5- or 6-membered monocyclic heteroaryl ring having 1 or 2 heteroatoms independently selected from N or S; a 3-, 4-, 5-, or 6-membered saturated carbocyclic ring; a 4-, 5-, or 6-membered saturated monocyclic heterocyclic ring having 1 or 2 heteroatoms independently selected from N; or a 5-, 6-, or 7-membered saturated bicyclic carbocyclic ring, each of which is optionally independently unsubstituted or substituted by 1, 2, or 3 instances of R.

[0047] In some embodiments of formula (I) provided by the present invention, Rd teeth, [ka] each of which may be independently unsubstituted or substituted with 1, 2, or 3 instances of R.

[0048] In some embodiments of formula (I) provided by the present invention, R is independently F, Cl, Br, C 1~3 Alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, -SC 1~3 Alkyl, -N(C 1~3 Alkyl)2, -NHC 1~3 Alkyl, -NH-cyclopropyl, -NH-cyclobutyl, -NH-cyclopentyl, -NH-cyclohexyl, -C 1~3 alkoxy, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl, or -O-cyclohexyl, each of which may be unsubstituted or substituted with 1, 2, 3 instances of D, F, Cl, or Br.

[0049] In some embodiments of formula (I) provided by the present invention, R is independently selected from F, Cl, Br, methyl, ethyl, propyl, i-propyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, cyclopentyl, -NH-cyclobutyl, -C 1~3 It may be selected from alkoxy, -O-cyclopropyl or -O-cyclobutyl, each of which may be unsubstituted or substituted with 1, 2, 3 instances of D, F, or Cl.

[0050] In some embodiments of Formula (I) provided by the present invention, R is independently selected from F, Cl, methyl, ethyl, methoxy, or cyclopropyl, each of which is optionally unsubstituted or substituted with 1, 2, or 3 instances of D or F.

[0051] In some embodiments of Formula (I) provided by the present invention, each R' is independently selected from the group consisting of 1~3It may be selected from alkyl, cyclopropyl, cyclobutyl, or cyclopentyl.

[0052] In some embodiments of Formula (I) provided by the present invention, each R' may be independently selected from methyl, ethyl, propyl, i-propyl, cyclopropyl, cyclobutyl, or cyclopentyl.

[0053] In some embodiments, the present invention further relates to a compound of formula (I) represented by formula (II) or formula (I-II): [ka] R 21 H, D, CN, C 1~3 Alkyl, C 1~3 Alkoxyl, C 3~6 Cycloalkyl, -(CH2) 0~2 -NHC 1~3 Alkyl, -(CH2) 0~2 N(C 1~3 alkyl)2, or a 3-6 membered saturated heterocyclic ring having 1 or 2 heteroatoms which may be independently selected from N, O or S, each of which is independently unsubstituted or has 1, 2 or 3 instances of D, OH, halogen, C 1~3 Alkyl, C 1~3 Alkoxyl or C 3~6 optionally substituted with cycloalkyl; R 22 each independently represents H, D, halogen, CN, NH2, OH, C 1~3 Alkyl, C 1~3 Alkoxyl, C 3~6 Cycloalkyl, -(CH2) 0~2 -NHC 1~3 Alkyl or -(CH2) 0~2 N(C 1~3 alkyl)2, each of which is independently unsubstituted or selected from 1, 2 or 3 instances of R z or R 21 and R22 together with the intervening atoms form a 5- to 7-membered heterocyclic ring having at least one nitrogen atom; R 25 each may independently be H, D, halogen, CN, OH, R", N(R")2, OR", or -SR", y is 0, 1, 2, 3 or 4; Each X or L may be independently selected from a covalent bond, -O-, -S-, -S(O)-, -NHS(O)2-, -S(O)2-, -CO-, -NH-, -CH2-, -CONH-, -NHCO-, -CONHCH2-, -NHCONH-, -NHCOCH2-, or -NHCOCH2CH2-, where each CH2 is independently unsubstituted or is selected from 1, 2, or 3 instances of D, halogen, C, 1~3 Alkyl or C 1~3 each NH is independently unsubstituted or substituted with C 1~3 may be substituted with alkyl; [ka] is a divalent bond or a trivalent bond, 1) [ka] If is a trivalent bond, R 23 does not exist, and R 24 each independently represents H, D, -C 0~3 Alkylene-N(R")2, -C 0~3 alkylene-OR″, or R″, each of which may be unsubstituted or substituted with 1, 2 or 3 instances of D or halogen; 2) [ka] If is a divalent bond, R 23 or R 24 each independently represents H, D, a halogen, -C 0~3 Alkylene-N(R")2, -C 0~3alkylene-OR″, or R″, each of which may be unsubstituted or substituted with 1, 2 or 3 instances of D or halogen; Each W is independently selected from the group consisting of C 1~3 alkyl, phenyl, a 4-6 membered saturated or partially saturated heterocyclic ring having 1 or 2 heteroatoms selected from N, O, or S, a 5- or 6 membered heteroaryl having 1 to 3 heteroatoms selected from N, O, or S, or a 3- to 6 membered saturated or partially saturated carbocyclic ring, each of which is independently unsubstituted or has 1, 2, or 3 instances of R w may be substituted with R w each independently represents D, halogen, OH, CN, NH2, C 1~3 Alkyl, C 1~3 Haloalkyl, C 3~6 Cycloalkyl, C 2~3 Alkenyl or C 2~3 alkynyl, each of which is independently unsubstituted or selected from 1, 2 or 3 instances of R z may be substituted with R z each may be independently selected from H, D, halogen, CN, -N(R")2, -OR", or R", Each of R" is independently 1~3 Alkyl or C 3~6 cycloalkyl, each of which may be unsubstituted or substituted with 1, 2 or 3 instances of halogen or D. A compound is provided.

[0054] In some embodiments of formula (I) provided by the present invention, R 21 are H, D, CN, NH2, OH, methyl, ethyl, propyl, i-propyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, -(CH2) 0~2 -NHCH3, -(CH2) 0~2 -NHCH2CH3, -(CH2) 0~2N(CH3)2, -(CH2) 0~2 N(CH2CH3)2, -(CH2) 0~2 a 4-membered saturated heterocyclic ring having 1 or 2 heteroatoms selected from N(CH3)(CH2CH3), N or O, a 5-membered saturated heterocyclic ring, or a 6-membered saturated heterocyclic ring, each of which is independently optionally unsubstituted or substituted with 1, 2 or 3 instances of D, OH, F, Cl, Br, methoxy, ethoxy, or propoxy; 22 are independently H, D, F, Cl, Br, CN, NH2, OH, methyl, ethyl, propyl, i-propyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, -(CH2) 0~2 -NHCH3, -(CH2) 0~2 -NHCH2CH3, -(CH2) 0~2 N(CH3)2, -(CH2) 0~2 N(CH2CH3)2 or -(CH2) 0~2 N(CHCHCH), each of which is independently unsubstituted or selected from 1, 2 or 3 instances of R z may be substituted with.

[0055] In some embodiments of formula (I) provided by the present invention, R 21 is selected from H, D, CN, NH, OH, methyl, ethyl, methoxy, cyclopropyl, cyclohexyl, N or O, a 4-membered saturated heterocyclic ring or a 5-membered saturated heterocyclic ring having 1 or 2 heteroatoms selected from each of which may be independently unsubstituted or substituted with 1, 2 or 3 instances of D, OH, F, or Cl; R 22each of R is independently selected from H, D, F, Cl, CN, NH, OH, methyl, ethyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, -NHCH, -CHNHCH, -CHCHNHCH, -CHNHCHCH, -N(CH), -CHN(CH), -(CHN(CH), -N(CHCHCH), -CHN(CHCHCH), or -(CH)N(CHCHCH), each of which is independently unsubstituted or selected from one, two or three instances of R. z may be substituted with.

[0056] In some embodiments of formula (I) provided by the present invention, R 21 teeth, [ka] wherein R is selected from 22 teeth, [ka] It is.

[0057] In some embodiments of formula (I) provided by the present invention, R 21 teeth, [ka] wherein R is selected from 22 teeth, [ka] It is.

[0058] In some embodiments of formula (I) provided by the present invention, R 21 and R 22 together with their intervening atoms form a 5-membered heterocyclic ring, a 6-membered heterocyclic ring, a 7-membered heterocyclic ring, a 5-membered carbocyclic ring, a 6-membered carbocyclic ring, or a 7-membered carbocyclic ring.

[0059] In some embodiments of Formula (I) provided by the present invention, the heterocyclic ring further comprises one heteroatom selected from an oxygen atom, a nitrogen atom, or a sulfur atom.

[0060] In some embodiments of formula (I) provided by the present invention, the heterocyclic ring is a 6-membered heterocyclic ring further comprising one oxygen atom, and said carbocyclic ring is a 6-membered carbocyclic ring.

[0061] In some embodiments of formula (I) provided by the present invention, R 25 Each of may independently be H, D, F, Cl, Br, CN, NH2, OH, methyl, ethyl, propyl, i-propyl, -S-methyl, -S-ethyl, -S-propyl, methoxy, ethoxy, or propoxy, each of which may be unsubstituted or substituted with 1, 2, 3 instances of D, F, Cl, or Br.

[0062] In some embodiments of formula (I) provided by the present invention, R 25 Each of may independently be H, D, F, Cl, methyl, ethyl, -S-methyl, -S-ethyl, methoxy, or ethoxy, each of which may be unsubstituted or substituted with 1, 2, or 3 instances of D or F.

[0063] In some embodiments of formula (I) provided by the present invention, R 25 Each of may independently be H, D, F, Cl, methyl, ethyl, -S-methyl, methoxy, or ethoxy, each of which may be unsubstituted or substituted with 1, 2, or 3 instances of F.

[0064] In some embodiments of Formula (I) provided by the present invention, each of X or L may be independently selected from a covalent bond, -O-, -CO-, -NH-, -CH2-, -CONH-, or -NHCO-.

[0065] In some embodiments of Formula (I) provided by the present invention, each X may be independently selected from -NH-, and each L may be independently selected from -O-, -NH-, -CONH-, or -NHCO-.

[0066] In some embodiments of formula (I) provided by the present invention, [ka] is a divalent bond, and R 23 or R 24 each may be independently selected from H, D, F, Cl, Br, -N(R")2, -CH2N(R")2, -(CH2)2N(R")2, -(CH2)3N(R")2, or R", each of which may be unsubstituted or substituted with 1, 2 or 3 instances of D, F, Cl, or Br.

[0067] In some embodiments of formula (I) provided by the present invention, [ka] is a divalent bond, and R 23 or R 24 each may be independently selected from H, D, F, Cl, methyl, ethyl, propyl, i-propyl, or cyclopropyl, each of which may be unsubstituted or substituted with 1, 2 or 3 instances of D, F or Cl.

[0068] In some embodiments of formula (I) provided by the present invention, [ka] is a divalent bond, and R 23 or R 24 may each be independently selected from H, D, F, or methyl, wherein said methyl may be unsubstituted or substituted with 1, 2 or 3 instances of D or F.

[0069] In some embodiments of formula (I) provided by the present invention, [ka] is a trivalent bond, and the R 23 Each of R 24 Each of may be independently selected from H, D, methyl, ethyl, propyl, iso-propyl, or cyclopropyl, each of which may be unsubstituted or substituted with 1, 2 or 3 instances of D, F, or Cl.

[0070] In some embodiments of formula (I) provided by the present invention, [ka] is a trivalent bond, and the R 23 Each of R 24 may each be independently selected from H, D, or methyl, wherein said methyl is unsubstituted or substituted with 1, 2 or 3 instances of D or F.

[0071] In some embodiments of formula (I) provided by the present invention, W may be independently selected from methyl; phenyl; a 4-, 5-, or 6-membered saturated heterocyclic ring having 1 or 2 heteroatoms selected from N, O, or S; a 5- or 6-membered heteroaryl having 1 or 2 heteroatoms selected from N or S; or a 3-, 4-, 5-, or 6-membered saturated carbocyclic ring.

[0072] In some embodiments of Formula (I) provided by the present invention, W may be independently selected from a 5- or 6-membered saturated heterocyclic ring having one nitrogen atom, a 5-membered heteroaryl having one nitrogen atom and optionally one additional sulfur atom, a 6-membered heteroaryl having one or two nitrogen atoms, a 3-membered saturated carbocyclic ring, a 4-membered saturated carbocyclic ring, a 5-membered saturated carbocyclic ring, or a 6-membered saturated carbocyclic ring.

[0073] In some embodiments of formula (I) provided by the present invention, R w each may be independently selected from D, F, Cl, Br, OH, OMe, CN, NH2, methyl, ethyl, propyl, i-propyl, methyl substituted with F or Cl, ethyl substituted with F or Cl, propyl substituted with F or Cl, i-propyl substituted with F or Cl, cyclopropyl, cyclobutyl, cyclopentyl, vinyl, or ethynyl, each of which is independently unsubstituted or selected from one, two, or three instances of R z may be substituted with.

[0074] In some embodiments of formula (I) provided by the present invention, R w may each be independently selected from D; F; Cl; methyl; methyl substituted with 1, 2 or 3 instances of F or D; methoxy; or cyclopropyl.

[0075] In some embodiments of formula (I) provided by the present invention, R z may each be independently selected from D, F, Cl, Br, CN, -N(R")2, -OR", or R".

[0076] In some embodiments of formula (I) provided by the present invention, R z may each be independently selected from D, F, Cl, Br, CN, NH2, methyl, ethyl, propyl, or i-propyl.

[0077] In some embodiments of formula (I) provided by the present invention, R z Each of may be independently selected from D, F, Cl, or methyl.

[0078] In some embodiments of Formula (I) provided by the present invention, each R″ can be independently methyl, ethyl, propyl, i-propyl, cyclopropyl, cyclobutyl, or cyclopentyl, each of which is optionally unsubstituted or substituted with 1, 2, or 3 instances of F, Cl, or D.

[0079] In some embodiments of Formula (I) provided by the present invention, each R″ can be independently methyl, ethyl, or cyclopropyl, each of which is optionally unsubstituted or substituted with 1, 2, or 3 instances of F or D.

[0080] In some embodiments of Formula (I) provided by the present invention, the compound independently comprises: N-(4-(3-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)imidazo[1,2-b]pyridazin-2-yl)phenyl)acrylamide; N-(4-(9-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-9H-purin-8-yl)phenyl)acrylamide; N-(4-(7-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)imidazo[1,2-b][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-3-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)phenyl)acrylamide; N-(4-(5-amino-3-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)imidazo[1,2-a]pyrimidin-2-yl)phenyl)acrylamide; N-(4-(4-amino-5-cyano-3-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[2,3-b]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-5-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-2,7-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)phenyl)acrylamide; N-(4-(4-amino-2-chloro-5-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)phenyl)acrylamide; N-(4-(4-methoxy-5-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)phenyl)acrylamide; N-(4-(4-cyclopropyl-5-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)phenyl)acrylamide; N-(4-(4-(difluoromethoxy)-5-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)phenyl)acrylamide; N-(4-(4-cyano-5-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)phenyl)acrylamide; N-(4-(4-amino-6-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)phenyl)acrylamide; N-(4-(4-amino-5-(4-(pyrrolidine-1-carbonyl)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-amino-5-(3-methoxy-4-((5-(methylamino)pyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(3-methoxy-4-(pyrrolidine-1-carbonyl)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(3-methoxy-4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(4-(pyrimidin-2-yloxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; 2-(4-acrylamidophenyl)-4-amino-3-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridine-7-carboxamide; N-(4-(4-amino-7-cyano-3-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclopropyl-2-methoxybenzamide; 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-(difluoromethoxy)-N-((1r,3r)-3-fluorocyclobutyl)benzamide; (S)-4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-fluoro-N-(tetrahydrofuran-3-yl)benzamide; 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclobutyl-2-methoxybenzamide; 4-(4-amino-6-(4-methacrylamidophenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-isobutylbenzamide; N-(4-(4-amino-5-(3-methoxy-4-(pyrimidin-2-yloxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(3-fluoro-4-(pyrimidin-2-yloxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(4-phenoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(4-(pyridin-2-yloxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(4-(cyclopentyloxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(4-(pyrimidin-2-yloxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)-2-fluorophenyl)acrylamide; N-(4-(4-amino-5-(4-(pyrimidin-2-yloxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)-3-fluorophenyl)acrylamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-(2-hydroxyethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclobutyl-2-methoxybenzamide; 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-isobutylbenzamide; 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclobutylbenzamide; 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclobutyl-2-fluorobenzamide; Methyl 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxybenzoate; 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(oxetan-3-yl)benzamide; 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-((1-methyl-1H-pyrazol-3-yl)methyl)benzamide; 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(cyclobutylmethyl)-2-methoxybenzamide; 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-((1s,3s)-3-hydroxycyclobutyl)-2-methoxybenzamide; 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-((1-cyanocyclopropyl)methyl)-2-methoxybenzamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-isobutylbenzamide; 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclobutyl-2-methoxy-N-methylbenzamide; 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclobutylcyclohex-3-ene-1-carboxamide; 4-(6-(4-acrylamido-3-fluorophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-isobutylbenzamide; 4-(6-(4-acrylamido-2-fluorophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-isobutylbenzamide; 4-(6-(4-acrylamido-3-methoxyphenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-isobutylbenzamide; 4-(6-(4-acrylamido-2-methoxyphenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-isobutylbenzamide; 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclopentyl-2-methoxybenzamide; 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2-methoxy-2-methylpropyl)benzamide; 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(2-hydroxy-2-methylpropyl)-2-methoxybenzamide; 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclohexyl-2-methoxybenzamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-(2-methoxyethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclobutyl-2-methoxybenzamide; 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-ethyl-2-methoxybenzamide; 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-isopropyl-2-methoxybenzamide; 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(2-(dimethylamino)ethyl)-2-methoxybenzamide; 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-((1s,3s)-3-methoxycyclobutyl)benzamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-isobutyl-2-methoxybenzamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclobutylbenzamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclobutyl-2-methoxybenzamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-(pyrimidin-2-yloxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(3-methoxy-4-(pyrimidin-2-yloxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; 4-(4-amino-6-(4-methacrylamidophenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; (E)-4-(4-amino-6-(4-(4-(dimethylamino)but-2-enamido)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclobutyl-2-(trifluoromethoxy)benzamide; 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclobutyl-2-methylbenzamide; 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclobutyl-2-ethoxybenzamide; 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclobutyl-2-methoxy-5-methylbenzamide; 4-(4-amino-6-(4-(2-(trifluoromethyl)acrylamido)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-amino-6-(4-(N-methylacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-methyl-N-(2,2,2-trifluoroethyl)benzamide; N-(4-(4-amino-5-(3-methoxy-4-(4-(trifluoromethyl)oxazol-2-yl)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-isobutyl-2-methoxybenzamide; N-(4-(4-amino-5-(2,2-dimethyl-4-oxo-3,4-dihydro-2H-benzo[e][1,3]oxazin-7-yl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(5-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepin-8-yl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclobutyl-2-methoxy-6-methylbenzamide; 4-(6-(4-acrylamido-2-methoxyphenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(6-(4-acrylamido-2-fluorophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(6-(4-acrylamido-2-methylphenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(6-(2-acryloyl-2-azaspiro[3.3]heptan-6-yl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclopropyl-2-methoxybenzamide; 4-(6-(6-acrylamidopyridin-3-yl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-(difluoromethoxy)-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-methyl-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclopentyl-2-methoxybenzamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-ethyl-2-methoxybenzamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclobutyl-2-methoxybenzamide; 4-(4-amino-7-cyano-2-(4-(2-fluoroacrylamide)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclobutylbenzamide; 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(3,3-difluorocyclobutyl)-2-methoxybenzamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(3,3-difluorocyclobutyl)-2-methoxybenzamide; 4-(4-amino-6-(4-(2-fluoroacrylamido)-2-methylphenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)-2-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclopropyl-2-methoxybenzamide; 4-(4-amino-7-cyano-2-(4-(2-fluoroacrylamide)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclopropyl-2-methoxybenzamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclopropyl-2-methoxybenzamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-(2,2,2-trifluoroethyl)benzamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-ethyl-2-methoxybenzamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-isopropyl-2-methoxybenzamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclopentyl-2-methoxybenzamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclohexyl-2-methoxybenzamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-((1-cyanocyclopropyl)methyl)-2-methoxybenzamide; 4-(2-(4-acrylamido-2-methoxyphenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 5-(4-acrylamidophenyl)-4-(3-methoxy-4-((6-methylpyridin-2-yl)oxy)phenyl)nicotinamide; 5-(4-acrylamidophenyl)-2-amino-4-(3-methoxy-4-((6-methylpyridin-2-yl)oxy)phenyl)-6-methylnicotinamide; N-(4-(4-amino-3-(3-methoxy-4-((6-methylpyridin-2-yl)oxy)phenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; N-(4-(4-amino-3-(3-methoxy-4-((6-methylpyridin-2-yl)oxy)phenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)methacrylamide; 1-(3-((4-amino-5-(3-methoxy-4-((6-methylpyridin-2-yl)oxy)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)piperidin-1-yl)prop-2-en-1-one; N-(4-(4-amino-3-(3-methoxy-4-((6-methylpyridin-2-yl)oxy)phenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)-2-fluorophenyl)acrylamide; 5-(4-acrylamidophenyl)-2-amino-4-(3-methoxy-4-((6-methylpyridin-2-yl)oxy)phenyl)-6-methylnicotinamide; 4-(4-amino-2-(4-methacrylamidophenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-3-yl)-N-isobutylbenzamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-3-yl)-N-isobutylbenzamide; N-(4-(4-cyano-6-(3-methoxy-4-((6-methylpyridin-2-yl)oxy)phenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)phenyl)acrylamide; N-(4-(4-chloro-6-(3-methoxy-4-((6-methylpyridin-2-yl)oxy)phenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)phenyl)acrylamide; N-(4-(4-methoxy-6-(3-methoxy-4-((6-methylpyridin-2-yl)oxy)phenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)phenyl)acrylamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-3-yl)-N-cyclobutylbenzamide; N-(4-(4-amino-7-oxo-3-(4-(pyrrolidine-1-carbonyl)phenyl)-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-3-yl)-N-(oxetan-3-yl)benzamide; N-(4-(4-amino-3-(3-methoxy-4-((6-methylpyridin-2-yl)oxy)phenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-amino-3-(4-(cyclopentyloxy)phenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-3-yl)-N-(pyrrolidin-3-yl)benzamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-3-yl)-N-(tetrahydro-2H-pyran-3-yl)benzamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-3-yl)-N-cyclobutyl-2-methoxybenzamide; N-(4-(4-amino-3-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)methacrylamide; N-(4-(4-amino-3-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-3-yl)-N-isobutyl-2-methoxybenzamide; N-(4-(4-amino-3-(4-((4-chloropyridin-2-yl)oxy)-3-methoxyphenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; 4-(4-amino-2-(4-(2-fluoroacrylamide)phenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-3-yl)-N-cyclobutyl-2-methoxybenzamide; N-(4-(4-amino-3-(4-(cyclopentyloxy)-3-methoxyphenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; N-(4-(4-amino-3-(4-cyclobutoxyphenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; N-(4-(4-amino-3-(4-(cyclohexyloxy)phenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; N-(4-(4-amino-3-(4-isobutoxyphenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; N-(4-(4-amino-3-(4-(cyclopentyloxy)-3-fluorophenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; 5-(4-acrylamidophenyl)-6-(3-methoxy-4-((6-methylpyridin-2-yl)oxy)phenyl)-1H-indazole-7-carboxamide; N-(4-(4-amino-7-oxo-3-(4-((tetrahydro-2H-pyran-4-yl)oxy)phenyl)-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; N-(4-(4-amino-3-(6-(cyclohexyloxy)pyridin-3-yl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; N-(4-(4-amino-3-(4-(cyclohexyl(methyl)amino)phenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; N-(4-(4-amino-3-(4-((4,4-difluorocyclohexyl)oxy)phenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; N-(4-(4-amino-3-(4-(cyclohexylthio)phenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; N-(4-(4-amino-3-(4-(cyclopentyloxy)phenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)methacrylamide; 4-(2-(4-acrylamido-2-fluorophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-amino-7-cyano-2-(2-fluoro-4-(2-fluoroacrylamide)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)-2-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclopropyl-2-methoxybenzamide; 4-(4-amino-6-(2-fluoro-4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclopropyl-2-methoxybenzamide; 4-(6-(4-acrylamido-2-methoxyphenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclopropyl-2-methoxybenzamide; 4-(6-(4-acrylamido-2-fluorophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclopropyl-2-methoxybenzamide; 4-(2-(4-acrylamido-2-methoxyphenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclopropyl-2-methoxybenzamide; 4-(2-(4-acrylamido-2-fluorophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclopropyl-2-methoxybenzamide; 4-(4-amino-7-cyano-2-(4-(2-fluoroacrylamide)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-isopropyl-2-methoxybenzamide; (S)-4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(3,3-difluorocyclopentyl)-2-methoxybenzamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-fluoro-N-(2,2,2-trifluoroethyl)benzamide; N-(4-(4-amino-7-cyano-3-(4-(cyclopentyloxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(1-methylcyclopropyl)benzamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(cyclopropylmethyl)-2-methoxybenzamide; N-(4-(4-amino-5-(4-(cyclopentyl(methyl)amino)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(4-cyclobutoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; 4-(4-amino-6-(6-ethynylpyridin-3-yl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-(2,2-difluorocyclopropyl)-2-methoxybenzamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-(3-fluorocyclobutyl)-2-methoxybenzamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(1-methylcyclopropyl)benzamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-(cyclopropylmethyl)-2-methoxybenzamide; 4-(4-amino-7-cyano-2-(4-(2-fluoroacrylamide)-2-methoxyphenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclopropyl-2-methoxybenzamide; N-(4-(4-amino-3-(4-cyclopropoxyphenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; N-(4-(4-amino-3-(4-((3-fluorocyclopentyl)oxy)phenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; N-(4-(4-amino-3-(4-((3,3-difluorocyclopentyl)oxy)phenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; N-(4-(4-amino-3-(4-((3-methylcyclohexyl)oxy)phenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; N-(4-(4-amino-3-(4-hydroxyphenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; N-(4-(4-amino-3-(4-(methoxymethoxy)phenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; N-(4-(4-amino-3-(1-(3,3-difluorocyclopentyl)-1H-indol-5-yl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; 4-(4-amino-6-(6-ethynyl-4-methylpyridin-3-yl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-amino-7-cyano-2-(6-ethynylpyridin-3-yl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-amino-7-cyano-2-(6-ethynylpyridin-3-yl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclopropyl-2-methoxybenzamide; N-(4-(4-amino-5-(4-(cyclopentyloxy)-3-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxybenzamide; 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(3-fluorocyclobutyl)-2-methoxybenzamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(3-fluorocyclobutyl)-2-methoxybenzamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(1-methylcyclopropyl)benzamide; 4-(6-(4-acrylamido-2-chlorophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclopropyl-2-methoxybenzamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-(3,3-difluorocyclobutyl)-2-methoxybenzamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-(2-fluoroethyl)-2-methoxybenzamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(3-methoxy-4-((6-methylpyridin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; 4-(2-(1-(1-acryloylpiperidin-4-yl)-1H-pyrazol-4-yl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(2,2-difluorocyclopropyl)-2-methoxybenzamide; 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(2-fluoroethyl)-2-methoxybenzamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(2-fluoroethyl)-2-methoxybenzamide; 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(2,2-difluoroethyl)-2-methoxybenzamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(2,2-difluoroethyl)-2-methoxybenzamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-(2,2-difluoroethyl)-2-methoxybenzamide; 4-(4-amino-6-(2-chloro-4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclopropyl-2-methoxybenzamide; 4-(2-(1-acryloylpyrrolidin-3-yl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(6-(1-(1-acryloylpiperidin-4-yl)-1H-pyrazol-4-yl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; N-(4-(4-amino-7-oxo-3-(4-(pyrrolidin-1-ylmethyl)phenyl)-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; 4-Amino-3-(4-(cyclohexyloxy)phenyl)-2-(6-ethynylpyridin-3-yl)-2,6-dihydro-7H-pyrazolo[3,4-d]pyridazin-7-one; 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-((1-fluorocyclopropyl)methyl)-2-methoxybenzamide; N-(4-(4-amino-5-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(4-cyclobutoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-amino-5-(4-cyclobutoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)methacrylamide; N-(4-(4-amino-5-(4-cyclobutoxy-3-fluorophenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; 4-(6-(1-acryloylpyrrolidin-3-yl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-((1-fluorocyclopropyl)methyl)-2-methoxybenzamide; 4-(2-(4-acrylamido-3-fluorophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclopropyl-2-methoxybenzamide; 4-(2-(4-acrylamido-3-fluorophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(2-(1-acryloyl-2,5-dihydro-1H-pyrrol-3-yl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; N-(4-(4-amino-3-bromo-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)-2-fluoroacrylamide; 1-(4-acrylamidophenyl)-3-amino-5-(3-methoxy-4-((6-methylpyridin-2-yl)oxy)phenyl)-1H-pyrazole-4-carboxamide; N-(4-(4-amino-7-oxo-3-(4-(pyrrolidin-1-yl)phenyl)-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; N-(4-(4-amino-3-(3-methoxy-4-((6-methylpyridin-2-yl)oxy)phenyl)-2H-pyrazolo[3,4-d]pyrimidin-2-yl)phenyl)acrylamide; N-(4-(4-amino-5-(6-cyclobutoxypyridin-3-yl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(4-cyclobutoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)-3-fluorophenyl)acrylamide; N-(4-(4-amino-5-(4-cyclobutoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)-3-methoxyphenyl)acrylamide; N-(4-(4-amino-5-(4-(cyclopropylmethoxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(4-cyclopropoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(4-(cyclohexylthio)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-3-bromo-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-5-(4-(2,2,2-trifluoroethoxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(4-isopropoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(4-(oxetan-3-yloxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(4-(cyclohexyloxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(4-((tetrahydro-2H-pyran-4-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(4-((3-methylcyclohexyl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(4-((4,4-dimethylcyclohexyl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxyphenyl)cyclopropanecarboxamide; N-(4-(4-amino-5-(4-(1-(cyclopropylamino)-2,2,2-trifluoroethyl)-3-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; 4-(4-amino-6-(2-fluoro-4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(3,3-difluorocyclobutyl)-2-methoxybenzamide; 4-(4-amino-7-cyano-2-(4-(2-fluoroacrylamide)phenyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclopropyl-2-methoxybenzamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-(2-fluoroethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclopropyl-2-methoxybenzamide; N-(4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxyphenyl)cyclopropanecarboxamide; N-(4-(4-amino-7-cyano-3-(4-((5-fluoropyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-5-(4-((3,3-difluorocyclopentyl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(4-cyclobutoxy-3-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(4-(1-(cyclopropylamino)-2,2,2-trifluoroethyl)-3-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-ethyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclopropyl-2-methoxybenzamide; N-(4-(4-amino-7-cyano-3-(4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(4-(1-(cyclopropylamino)-2,2,2-trifluoroethyl)-3-methoxyphenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-5-(4-((4,4-difluorocyclohexyl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(4-((1-methylazetidin-3-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(4-(3-(dimethylamino)cyclobutoxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-amino-6-(2-fluoro-4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(3-fluorocyclobutyl)-2-methoxybenzamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)-2-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-((1-fluorocyclopropyl)methyl)-2-methoxybenzamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)-2-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(2,2-difluoroethyl)-2-methoxybenzamide; 4-(4-amino-6-(6-(2-fluoroacrylamide)pyridin-3-yl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-amino-6-(3-fluoro-4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-amino-6-(4-(2-fluoroacrylamido)-3-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)-2-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(3-fluorocyclobutyl)-2-methoxybenzamide; 4-(4-amino-6-(2-fluoro-4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(1-methylcyclopropyl)benzamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)-2-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(1-methylcyclopropyl)benzamide; 4-(4-amino-6-(2-fluoro-4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-((1-fluorocyclopropyl)methyl)-2-methoxybenzamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)-2-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(2,2-difluorocyclopropyl)-2-methoxybenzamide; N-(4-(4-amino-5-(4-(bicyclo[3.1.0]hexan-3-yloxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(4-((3-fluorocyclopentyl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide N-(5-(4-amino-5-(4-cyclobutoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)pyridin-2-yl)acrylamide; N-(4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)phenyl)cyclopropanecarboxamide; N-(4-(4-amino-5-(4-(pyrrolidin-1-yl)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxyphenyl)cyclobutanecarboxamide; N-(4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxyphenyl)cyclopentanecarboxamide; 4-(4-amino-7-cyano-2-(2-fluoro-4-(2-fluoroacrylamide)phenyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclopropyl-2-methoxybenzamide; 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(1-cyanocyclopropyl)-2-methoxybenzamide; 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(bicyclo[1.1.1]pentan-1-yl)-2-methoxybenzamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(bicyclo[1.1.1]pentan-1-yl)-2-methoxybenzamide; 4-(4-amino-6-(2-fluoro-4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(2,2-difluorocyclopropyl)-2-methoxybenzamide; N-(4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxyphenyl)cyclobutanecarboxamide; N-(4-(4-amino-5-(4-(3-methoxycyclobutoxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(4-(spiro[2.3]hexan-5-yloxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; 4-(2-(4-acrylamido-2-methoxyphenyl)-4-amino-7-cyano-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-(3,3-difluorocyclobutyl)-2-methoxybenzamide; N-(4-(4-amino-7-cyano-3-(3-methoxy-4-propionamidophenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-(2-fluoroethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-(3,3-difluorocyclobutyl)-2-methoxybenzamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(1-cyanocyclopropyl)-2-methoxybenzamide; N-(4-(4-amino-5-(4-(cyclobutylamino)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; 4-(2-(4-acrylamido-2-fluorophenyl)-4-amino-7-cyano-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-(3,3-difluorocyclobutyl)-2-methoxybenzamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-isopropyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-(3,3-difluorocyclobutyl)-2-methoxybenzamide; N-(4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxyphenyl)-N-methylcyclopropanecarboxamide; N-(4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)phenyl)cyclopropanecarboxamide; N-(4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxyphenyl)-3,3-difluorocyclobutane-1-carboxamide; N-(4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxyphenyl)-1-methylcyclopropane-1-carboxamide; N-(4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxyphenyl)-1-fluorocyclopropane-1-carboxamide; N-(4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxyphenyl)-1-(trifluoromethyl)cyclopropane-1-carboxamide; 4-(4-amino-6-(2-fluoro-4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(2,2-difluoroethyl)-2-methoxybenzamide; N-(4-(4-amino-7-cyano-3-(4-cyclobutoxy-3-methoxyphenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxyphenyl)-2,2-difluorocyclopropane-1-carboxamide; N-(4-(4-amino-7-cyano-3-(4-(3-cyclopropylureido)-3-methoxyphenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(1,1,1-trifluoropropan-2-yl)benzamide; 4-(4-amino-6-(3-((dimethylamino)methyl)-4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; N-(4-(4-amino-5-(4-(azetidin-1-yl)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(4-(3-cyclopropylureido)-3-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxyphenyl)azetidine-1-carboxamide; N-(4-(4-amino-7-cyano-3-(4-(cyclobutylamino)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxyphenyl)azetidine-1-carboxamide; 4-(2-(4-acrylamido-3-((dimethylamino)methyl)phenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)-2-fluoroacrylamide; 4-(4-amino-7-cyano-2-(4-(2-fluoroacrylamide)phenyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-amino-7-cyano-2-(4-(2-fluoroacrylamide)phenyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(1-(trifluoromethyl)cyclopropyl)benzamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-(2-methoxyethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-(3,3-difluorocyclobutyl)-2-methoxybenzamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-(2-fluoroethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(1-(trifluoromethyl)cyclopropyl)benzamide; 4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(1-(trifluoromethyl)cyclopropyl)benzamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(1-(trifluoromethyl)cyclopropyl)benzamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-((1-(trifluoromethyl)cyclopropyl)methyl)benzamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(3,3,3-trifluoropropyl)benzamide; 4-(6-(4-acrylamido-3-((dimethylamino)methyl)phenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(6-(4-acrylamido-2-((dimethylamino)methyl)phenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; N-(4-(4-amino-5-(3-methoxy-4-(pyrrolidin-1-yl)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(4-(cyclobutylamino)-3-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-(pyrrolidin-1-yl)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(3-methoxy-4-(pyrrolidin-1-yl)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(4-(cyclobutylamino)-3-methoxyphenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-(2-methoxyethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-amino-7-cyano-2-(4-(2-fluoroacrylamide)phenyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-(3,3-difluorocyclobutyl)-2-methoxybenzamide; 4-(4-amino-7-cyano-2-(4-(2-fluoroacrylamide)phenyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-(2,2-difluorocyclopropyl)-2-methoxybenzamide; 4-(4-amino-7-cyano-2-(4-(2-fluoroacrylamide)phenyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(1-methylcyclopropyl)benzamide; N-(4-(4-amino-5-(1-methyl-1H-indol-5-yl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(1-methyl-1H-indol-5-yl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(2,2,2-trifluoroethyl)benzamide; N-(4-(4-amino-5-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(1-methyl-1H-indol-5-yl)-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-3-(benzo[b]thiophen-2-yl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-isopropyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(3-fluorobicyclo[1.1.1]pentan-1-yl)-2-methoxybenzamide; N-(4-(4-amino-5-(benzo[b]thiophen-2-yl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-amino-5-(benzo[b]thiophen-2-yl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-((3,3-difluorocyclobutyl)methyl)-2-methoxybenzamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-fluoro-N-(2,2,2-trifluoroethyl)benzamide; N-(4-(4-amino-5-(3-fluoro-4-((5-fluoropyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(3-(trifluoromethyl)bicyclo[1.1.1]pentan-1-yl)benzamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(1,1-difluoropropan-2-yl)-2-methoxybenzamide; N-(4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxyphenyl)-3,3-difluorocyclobutane-1-carboxamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-(bicyclo[1.1.1]pentan-1-yl)-2-methoxybenzamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclopropyl-2-methoxybenzamide; N-(4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-fluorophenyl)cyclopropanecarboxamide; 4-(3-acrylamido-12-amino-9-cyano-6,7-dihydro-5H-benzo[c]pyrido[3',4':4,5]pyrrolo[1,2-a]azepin-13-yl)-N-(3,3-difluorocyclobutyl)-2-methoxybenzamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-(methylthio)-N-(2,2,2-trifluoroethyl)benzamide; N-(4-(4-amino-5-(2-(4-methoxyphenyl)thiazol-5-yl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-amino-5-(2-(4-methoxyphenyl)thiazol-5-yl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-cyclopropyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-(methylthio)-N-(2,2,2-trifluoroethyl)benzamide; N-(4-(4-amino-5-(3-methoxy-4-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(3-methoxy-4-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; 4-(4-amino-6-(2-fluoro-4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(1-(trifluoromethyl)cyclopropyl)benzamide; 4-(4-amino-6-(2-fluoro-4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(bicyclo[1.1.1]pentan-1-yl)-2-methoxybenzamide; 4-(4-amino-6-(2-fluoro-4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-((1-(trifluoromethyl)cyclopropyl)methyl)benzamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-cyclopropyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclopropyl-2-methoxybenzamide; N-(4-(4-amino-5-(3-methoxy-4-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; 4-(4-amino-6-(2-fluoro-4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-((1-(trifluoromethyl)cyclopropyl)methyl)benzamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(2,2-difluoropropyl)-2-methoxybenzamide; N-(4-(4-amino-5-(4-(azetidine-1-carbonyl)-3-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(3-fluoro-4-((2-methylpyrimidin-4-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-amino-5-(3-fluoro-4-((2-methylpyrimidin-4-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(1-oxo-2-(2,2,2-trifluoroethyl)-1,2-dihydroisoquinolin-6-yl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(1-oxo-2-(2,2,2-trifluoroethyl)isoindolin-5-yl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-((1-fluorocyclopropyl)methyl)-2-(methoxy-d3)benzamide; N-(4-(4-amino-5-(3-fluoro-4-((6-methylpyrazin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-amino-5-(3-fluoro-4-((6-methylpyrazin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(3-fluoro-4-((5-methylpyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-amino-5-(3-fluoro-4-((5-methylpyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(3-fluoro-4-(pyrimidin-2-yloxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-amino-3-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-2H-pyrazolo[3,4-d]pyrimidin-2-yl)phenyl)methacrylamide; N-(4-(4-amino-5-(3-fluoro-4-((4-methoxypyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-amino-5-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)-3-fluorophenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-amino-5-(3-fluoro-4-((6-methylpyrimidin-4-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-amino-5-(3-fluoro-4-((6-methylpyrimidin-4-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-((1-fluorocyclopropyl)methyl)benzamide; N-(4-(4-amino-5-(3-fluoro-4-((4-methylpyrimidin-2-yl)thio)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-amino-5-(3-fluoro-4-((4-methylpyrimidin-2-yl)thio)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-amino-5-(4-((4-cyclopropylpyrimidin-2-yl)oxy)-3-fluorophenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide N-(4-(4-amino-5-(4-((4-cyclopropylpyrimidin-2-yl)oxy)-3-fluorophenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(3-fluoro-4-(imidazo[1,2-c]pyrimidin-5-yloxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-amino-5-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)-3-fluorophenyl)methacrylamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-phenylbenzamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(pyridin-2-yl)benzamide; N-(4-(4-amino-5-(3-fluoro-4-(methyl(4-methylpyrimidin-2-yl)amino)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-amino-5-(3-fluoro-4-((4-(trifluoromethyl)pyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-amino-5-(3-fluoro-4-((4-(trifluoromethyl)pyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; 4-(4-amino-6-(4-(but-2-ynamido)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(1-(trifluoromethyl)cyclopropyl)benzamide; 4-(4-amino-6-(4-propiolamidophenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(1-(trifluoromethyl)cyclopropyl)benzamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(tert-butyl)-2-methoxybenzamide; N-(4-(4-amino-5-(4-((4-ethylpyrimidin-2-yl)oxy)-3-fluorophenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-amino-5-(4-((4-ethylpyrimidin-2-yl)oxy)-3-fluorophenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(3-fluoro-4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-amino-5-(3-fluoro-4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(3-fluoro-4-((4-methylpyrimidin-2-yl)amino)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-amino-5-(3-fluoro-4-((4-methylpyrimidin-2-yl)amino)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(3-fluoro-4-((4-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-amino-5-(3-fluoro-4-((4-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(4-(4-fluorobenzoyl)-3-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)methacrylamide; N-(4-(4-amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)but-2-ynamide; N-(4-(4-amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)propiolamide; N-(4-(4-amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)ethenesulfonamide; (E)-N-(4-(4-amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-4-(dimethylamino)but-2-enamide; 1-(4-(4-amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one; (E)-N-(4-(4-amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)buta-2-enamide 4-(4-amino-6-(4-(2-fluoroacrylamide)-2-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(1-(trifluoromethyl)cyclopropyl)benzamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)-2-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(3-fluorobicyclo[1.1.1]pentan-1-yl)-2-methoxybenzamide; N-(4-(4-amino-5-(3-fluoro-4-(methyl(4-methylpyrimidin-2-yl)amino)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(4-benzoyl-3-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(4-(4,4-difluorocyclohexane-1-carbonyl)-3-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; 1-(4-(4-amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)piperidin-1-yl)prop-2-en-1-one; 1-(4-(4-(4-amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)-1H-pyrazol-1-yl)piperidin-1-yl)prop-2-en-1-one; N-(4-(4-amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-((dimethylamino)methyl)acrylamide; N-(4-(4-amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-chloroacetamide; N-(4-(4-amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-chloroacrylamide; (Z)-4-((4-(4-amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)amino)-4-oxobut-2-enoic acid; 4-(4-amino-6-(4-(2-fluoroacrylamide)-2-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(bicyclo[1.1.1]pentan-1-yl)-2-methoxybenzamide; 4-(4-amino-6-(2-fluoro-4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(3-fluorobicyclo[1.1.1]pentan-1-yl)-2-methoxybenzamide; N-(4-(4-amino-5-(4-((4-aminopyrimidin-2-yl)oxy)-3-fluorophenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; 4-(4-amino-6-(2-fluoro-4-methacrylamidophenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(1-(trifluoromethyl)cyclopropyl)benzamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-5-(4-(cyclohexanecarbonyl)-3-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)-2-(trifluoromethyl)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(1-(trifluoromethyl)cyclopropyl)benzamide; N-(4-(4-amino-5-(3-fluoro-4-((4-(methylamino)pyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)-3-fluorophenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((6-methylpyridin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)-3-fluorophenyl)-2-fluoroacrylamide; N-(4-(4-amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)-3-methylphenyl)-2-fluoroacrylamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-5-(2-(1-methylcyclopropyl)benzo[d]thiazol-6-yl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-5-(3-methoxy-4-((1-methylcyclohexyl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-(pyrimidin-2-yloxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; 4-(4-amino-6-(2-chloro-4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(1-(trifluoromethyl)cyclopropyl)benzamide; 4-(4-amino-6-(4-(2-fluoroacrylamido)-2-methylphenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(1-(trifluoromethyl)cyclopropyl)benzamide; 4-(4-amino-6-(2-chloro-4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(1-(trifluoro-4-(4-amino-6-(2-chloro-4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(1-(trifluoromethyl)cyclopropyl)benzamide; N-(4-(4-amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)-3-chlorophenyl)-2-fluoroacrylamide; N-(4-(4-amino-5-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)-3-methoxyphenyl)methacrylamide; N-(4-(4-amino-5-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)-3-methylphenyl)methacrylamide; N-(4-(4-amino-5-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-amino-5-(3-fluoro-4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)methacrylamide; N-(4-(4-amino-5-(3-fluoro-4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-amino-5-(3-fluoro-4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)but-2-ynamide; N-(4-(4-amino-5-(3-fluoro-4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)propiolamide; N-(4-(4-amino-5-(3-methoxy-4-(1-methyl-1H-imidazole-2-carbonyl)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(4-((5-fluoropyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)-3-methoxyphenyl)-2-fluoroacrylamide; N-(4-(4-amino-7-cyano-3-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)-3-fluorophenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-(pyrimidin-2-yloxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(4-((4-ethylpyrimidin-2-yl)oxy)-3-fluorophenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-(pyridin-2-yloxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((6-methylpyridin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-(pyrimidin-2-yloxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; 4-(4-amino-7-cyano-2-(2-fluoro-4-methacrylamidophenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; N-(4-(4-amino-3-(3-chloro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(3-methyl-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(3,5-difluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(4-((4,5-dimethylpyrimidin-2-yl)oxy)-3-fluorophenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((5-fluoropyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-(pyridin-2-yloxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((5-fluoropyridin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(4-((4,5-dimethylpyrimidin-2-yl)oxy)-3-fluorophenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(4-(cyclohexyloxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; 4-(4-amino-7-cyano-2-(2-fluoro-4-methacrylamidophenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(1-(trifluoromethyl)cyclopropyl)benzamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-(pyridin-2-yloxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-(pyridin-2-yloxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((5-fluoropyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-amino-3-(3-chloro-4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-3-(4-((6-chloropyridin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(2,5-difluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(2,3-difluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-2-fluoro-3-methylphenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(2-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((5-fluoropyridin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(4-((5-fluoropyridin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)-3-methylphenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(3,5-difluoro-4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)acrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(4-((5-fluoropyridin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(2,3-difluoro-4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(4-(cyclohexyloxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(4-(cyclohexanecarbonyl)-3-fluorophenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-(thiazol-2-yloxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((4-methylthiazol-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((4-(trifluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((4-(trifluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-2,3-difluorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((5-fluoro-6-methylpyridin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((5-fluoro-6-methylpyridin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-2,3-difluorophenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(4-(cyclohexyloxy)-3-fluorophenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(4-((1,5-dimethyl-1H-pyrazol-3-yl)oxy)-3-fluorophenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((4-(trifluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((4-(trifluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(4-((4,6-dimethylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((1-methyl-1H-pyrazol-5-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(3-methyl-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(4-((1-cyclopropyl-1H-pyrazol-3-yl)oxy)-3-fluorophenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-3-(3-chloro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((6-methylpyridin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; 4-(3-acrylamido-12-amino-9-cyano-6,7-dihydrobenzo[f]pyrido[3',4':4,5]pyrrolo[1,2-d][1,4]oxazepin-13-yl)-N-(3,3-difluorocyclobutyl)-2-methoxybenzamide; N-(4-(4-amino-3-(3-chloro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)acrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(4-(cyclohexyloxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-amino-5-(4-(cyclohexyloxy)-3-fluorophenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-amino-5-(4-(cyclohexyloxy)-3-fluorophenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(4-(cyclohexyloxy)-3-fluorophenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-5-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-amino-7-cyano-2-(4-(2-fluoroacrylamide)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-amino-6-(2-fluoro-4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(3,3-difluorocyclobutyl)benzamide; N-(4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxyphenyl)-2,2-difluorocyclopropane-1-carboxamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-amino-5-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)methacrylamide; 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-(methyl-d3)-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; 4-(3-acrylamido-12-amino-9-cyano-6,7-dihydrobenzo[f]pyrido[3',4':4,5]pyrrolo[1,2-d][1,4]oxazepin-13-yl)-N-(3,3-difluorocyclobutyl)-2-methoxybenzamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(3-methyl-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((6-methylpyridin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)-3-fluorophenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((4-(trifluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)-2-fluoroacrylamide; N-(4-(4-amino-7-cyano-3-(4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)-2-fluoroacrylamide; N-(4-(4-amino-7-cyano-3-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)-2-fluoroacrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)-2-fluoroacrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((6-methylpyridin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)-2-fluoroacrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)-2-fluoroacrylamide; N-(4-(4-amino-7-cyano-3-(4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)-2-fluoroacrylamide; N-(4-(4-amino-7-cyano-3-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)-2-fluoroacrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)-2-fluoroacrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((6-methylpyridin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)-2-fluoroacrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)-2-fluoroacrylamide; N-(4-(4-amino-7-cyano-3-(4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)-2-fluoroacrylamide; N-(4-(4-amino-7-cyano-3-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)-2-fluoroacrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)-2-fluoroacrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((6-methylpyridin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)-2-fluoroacrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)acrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)acrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((6-methylpyridin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)acrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)acrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)acrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((6-methylpyridin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)acrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)acrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((6-methylpyridin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)-2-methylprop-2-enethioamide; N-(4-(4-amino-7-cyano-3-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-1-ethyl-3-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-1-(2-fluoroethyl)-3-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(4-((4-(difluoromethyl)-5-fluoropyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(4-((4-(difluoromethyl)-5-fluoropyrimidin-2-yl)oxy)-3-fluorophenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-3-(3-chloro-5-fluoro-4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3,5-difluorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluoro-5-methylphenyl)methacrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-(trifluoromethyl)phenyl)methacrylamide; N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)-3,5-difluorophenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-3-(4-((5-chloro-4-(trifluoromethyl)pyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-3-(4-((5-chloro-4-(trifluoromethyl)pyrimidin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((4-(trifluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((4-(trifluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((4-(trifluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide; N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)but-2-ynamide; N-(4-(4-amino-3-(4-((5-chloro-4-(difluoromethyl)pyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-3-(4-((5-chloro-4-(difluoromethyl)pyrimidin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-amino-3-(4-((5-chloro-6-methylpyridin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-3-(4-((5-chloro-6-methylpyridin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-3-(3-chloro-4-((5-chloro-4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)-3-methylphenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)acrylamide; N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)acrylamide; N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)-2-fluoroacrylamide; N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)-2-fluoroacrylamide; N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)acrylamide; N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)acrylamide; N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)-2-fluoroacrylamide; N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)-2-fluoroacrylamide; N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)acrylamide; N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)acrylamide; N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)-2-fluoroacrylamide; or N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)-2-fluoroacrylamide is selected from.

[0081] The present invention further provides pharmaceutical compositions comprising at least one compound of formula (I) and a pharma- ceutically acceptable carrier.

[0082] In some embodiments of the pharmaceutical compositions comprising a compound of Formula (I) provided by the present invention, the pharmaceutical composition comprises a compound of the Examples and a pharma- ceutically acceptable carrier.

[0083] In some embodiments of the pharmaceutical compositions comprising a compound of Formula (I) provided by the present invention, the pharmaceutical composition comprises a compound of Table 1 and a pharma- ceutically acceptable carrier.

[0084] In some embodiments of the pharmaceutical compositions comprising a compound of Formula (I) provided by the present invention, the pharmaceutical composition comprises a compound of Table 2 and a pharma- ceutically acceptable carrier.

[0085] The present invention further provides a method for inhibiting FGFR2 signaling activity in a subject, comprising administering a therapeutically effective amount of a compound of formula (I) and pharmaceutical compositions thereof to a subject in need thereof.

[0086] The present invention further provides a method for treating an FGFR2-mediated disorder in a subject, comprising administering a therapeutically effective amount of a compound of formula (I) and pharmaceutical compositions thereof to a subject in need thereof.

[0087] The present invention further provides a method of treating a disorder in a subject, comprising administering a therapeutically effective amount of a compound of formula (I) and pharmaceutical compositions thereof to a subject in need thereof, wherein the disorder is bile duct cancer, liver cancer, breast cancer, prostate cancer, lung cancer, thyroid cancer, gastric cancer, ovarian cancer, rectal cancer, endometrial cancer, or urothelial cancer.

[0088] In some embodiments of the method of treating a disorder in a subject, the disorder is cholangiocarcinoma.

[0089] In some embodiments of the above methods of treating a disorder in a subject, the cholangiocarcinoma is intrahepatic cholangiocarcinoma.

[0090] In some embodiments of the methods of treating a disorder in a subject, the disorder is liver cancer.

[0091] In some embodiments of the methods of treating a disorder in a subject, the liver cancer is hepatocellular carcinoma.

[0092] In some embodiments of the methods of treating a disorder in a subject, the disorder is lung cancer.

[0093] In some embodiments of the methods of treating a disorder in a subject, the lung cancer is squamous cell lung carcinoma or non-small cell lung cancer.

[0094] Representative compounds of the above formula I are shown in Examples, Tables 1 and 2.

[0095] The compounds provided by the present invention are highly potent against the kinase FGFR-2 in both enzymatic and cellular assays, and highly selective against the same family kinases FGFR-1 and FGFR-3. Many compounds of the present invention show good to excellent exposure in rat PK experiments. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0096] definition The following description is made with the understanding that the present disclosure should be considered as an illustration of the claimed subject matter and is not intended to limit the scope of the appended claims to the specific embodiments illustrated. The headings used in this disclosure are provided for convenience and should not be considered to limit the scope of the claims in any way. The embodiments shown under any heading may be combined with the embodiments of any other heading shown.

[0097] All technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art unless otherwise defined. It should be noted that, as used in this disclosure, the singular forms "a," "and," and "the" include plural referents unless the context clearly contradicts. Thus, "the compound" includes a plurality of such compounds, "the assay" includes one or more assays, and so forth.

[0098] As used in this disclosure, the following words, phrases and symbols are generally intended to have the meanings set forth below, unless the context in which they are used indicates otherwise.

[0099] Unless otherwise indicated, a dash "-" used herein at the beginning or end of a chemical group is used for convenience to indicate the point of attachment of a substituent. For example, -OH is attached through a carbon atom. Chemical groups may be depicted with or without one or more dashes without losing their normal meaning. A wavy line drawn across a line in a structure indicates the point of attachment of the group. No directionality is indicated or implied by the order in which chemical groups are described or named, unless chemically or structurally required. A solid line emanating from the center of a ring indicates that the point of attachment of a substituent on the ring may be at any ring atom.

[0100] Prefix “C” m~n ", as used herein, unless otherwise specified, indicates that the group described thereafter has m to n carbon atoms. For example, "C 1~6 "Alkyl" indicates that the alkyl group has 1 to 6 carbon atoms. Similarly, the term "m- to n-membered" ring, where m and n are integers and refer to the range of m to n, e.g., a "3- to 7-membered heterocyclic ring," refers to a ring containing 3 to 7 atoms, where up to 80% of the 3 to 7 atoms may be heteroatoms, e.g., N, O, or S, and the remaining atoms are carbon.

[0101] As used herein, the term "aliphatic" or "aliphatic group," unless otherwise indicated, means a straight-chain (i.e., unbranched) or branched, substituted or unsubstituted hydrocarbon chain that is fully saturated or contains one or more units of unsaturation, or a monocyclic or bicyclic hydrocarbon (also referred to herein as a "carbocyclic ring" or "alicyclic ring") that is fully saturated or contains one or more units of unsaturation but is not aromatic and has a single point of attachment to the remainder of the molecule. Unless otherwise specified, an aliphatic group contains 1-6 aliphatic carbon atoms. In some embodiments, an aliphatic group contains 1-5 aliphatic carbon atoms. In other embodiments, an aliphatic group contains 1-4 aliphatic carbon atoms. In still other embodiments, an aliphatic group contains 1-3 aliphatic carbon atoms, and in yet other embodiments, an aliphatic group contains 1-2 aliphatic carbon atoms. In some embodiments, "alicyclic" (or "carbocycle") refers to a monocyclic C3-C6 hydrocarbon that is fully saturated or contains one or more units of unsaturation, but is not aromatic, and has a single point of attachment to the rest of the molecule. Suitable aliphatic groups include, but are not limited to, linear or branched, substituted or unsubstituted alkyl, alkenyl, alkynyl groups, and hybrid forms thereof, such as (cycloalkyl)alkyl, (cycloalkenyl)alkyl, or (cycloalkyl)alkenyl.

[0102] Also, some commonly used alternative chemical names may or may not be used. For example, divalent groups such as divalent "alkyl" groups, divalent "aryl" groups, etc. may be referred to as "alkylene" or "alkylenyl" or alkylyl groups, or "arylene" or "arylenyl" or arylyl groups, "phenyl" or "phenylene" groups, respectively.

[0103] "Compounds provided herein" or "compounds described herein" or "compounds disclosed herein" or "compounds of the disclosure" refer to compounds of formula I, II, III, IV, V, VI, VII, II, or I-II.

[0104] In certain embodiments, the term "about" when directed to a value or parameter itself includes the indicated amount ±10%, ±5%, or ±1%. Also, the term "about X" includes the description of "X."

[0105] As used herein, "adjacent atoms" refers to atoms that are immediately next to each other. For example, in "C1-C2-C3-C4," atom C1 is adjacent to atom C2, atom C2 is adjacent to atoms C1 and C3, and so on.

[0106] "Optional" or "optionally" or "may" means that the described event or circumstance may or may not occur, and that the description includes both cases where said event or circumstance occurs and cases where it does not occur. Also, the term "optionally substituted" means that any one or more hydrogen atoms on a specified atom or group may or may not be replaced by a non-hydrogen moiety.

[0107] The term "substituted" means that one or more hydrogen atoms on the specified atom or group are replaced with one or more substituents other than hydrogen, provided that the replacement does not exceed the normal valence of the specified atom. For example, one or more hydrogens, such as alkyl, alkylene, alkenyl, alkynyl, OH, or NH2, can be replaced with one or more substituents. Substituents include, but are not limited to, alkyl, alkenyl, alkynyl, alkoxy, acyl, amino, amido, amidino, aryl, azido, carbamoyl, carboxyl, carboxyl ester, cyano, guanidino, halo, haloalkyl, heteroalkyl, heteroaryl, heterocyclyl, hydroxy, hydrazino, imino, oxo, nitro, alkylsulfinyl, sulfonic acid, alkylsulfonyl, thiocyanate, thiol, thione, or combinations thereof. Similar indefinite structures arrived at by defining a substituent with an infinite number of additional substituents (e.g., a substituted aryl with a substituted alkyl, which is itself substituted with a substituted aryl group, which is further substituted with a substituted heteroalkyl group, etc.) are not intended for inclusion herein. Unless otherwise specified, the maximum number of consecutive substitutions in the compounds described herein is three. For example, consecutive substitution of a substituted aryl group with two other substituted aryl groups is limited to ((substituted aryl)substituted aryl)substituted aryl. Similarly, the above definition is not intended to include impermissible substitution patterns (e.g., a methyl substituted with five fluorines or a heteroaryl group with two adjacent oxygen ring atoms). Such impermissible substitution patterns are well known to those of skill in the art. Whenever used to modify a chemical group, "substituted" may describe other chemical groups defined herein. For example, the term "substituted aryl" includes, but is not limited to, "alkylaryl". Unless otherwise specified, when a group is described as being optionally substituted, none of the substituents of the group are themselves substituted.

[0108] As used herein, the term "C 1~6 (or C 1~4Or C 1~3 )" a divalent saturated or unsaturated, straight or branched hydrocarbon chain" refers to divalent alkylene, alkenylene, and alkynylene chains, which are straight or branched, as defined herein.

[0109] The term "alkylene," as used herein, unless otherwise indicated, refers to a divalent alkyl group. An "alkylene chain" is a polymethylene group, i.e., -(CH2) n -, where n is a positive integer, preferably 1 to 6, 1 to 4, 1 to 3, 1 to 2, or 2 to 3. A substituted alkylene chain is a polymethylene group in which one or more methylene hydrogen atoms have been replaced with a substituent. Suitable substituents include those described below for substituted aliphatic groups.

[0110] The term "alkenylene" as used herein, unless otherwise indicated, refers to a divalent alkenyl group. A substituted alkenylene chain is a polymethylene group containing at least one double bond in which one or more hydrogen atoms are replaced with a substituent. Suitable substituents include those described below for substituted aliphatic groups.

[0111] The terms "alkylene," "arylene," "cycloalkylene," "heteroarylene," "heterocycloalkylene," and other similar terms with the suffix "-ylene," as used herein, unless otherwise indicated, refer to a divalent linked version of the group that the suffix modifies. For example, "alkylene" is a divalent alkyl group that links the groups to which it is attached.

[0112] The term "alkyl," as used herein, unless otherwise indicated, refers to a monovalent aliphatic hydrocarbon radical having straight-chain, branched-chain, monocyclic, or polycyclic moieties, or combinations thereof, which may be substituted at one or more carbons of the straight-chain, branched-chain, monocyclic, or polycyclic moieties, or combinations thereof, with one or more substituents at each carbon, which are independently C1-C6 alkyl. Examples of "alkyl" groups include methyl, ethyl, propyl, isopropyl, butyl, iso-butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, norbornyl, and "butyl" includes n-butyl (i.e., -(CH2)3CH3), sec-butyl (i.e., -CH(CH3)CH2CH3), isobutyl (i.e., -CH2CH(CH3)2), and the like. "Propyl" includes n-propyl (i.e., -(CH2)2CH3) and isopropyl (i.e., -CH(CH3)2), and pentyl includes 2-pentyl, isopentyl, or neopentyl.

[0113] The term "alkenyl" refers to an aliphatic group containing at least one carbon-carbon double bond (C=C) and having 2 to 15 carbon atoms (i.e., C 2~15 alkenyl) or an aliphatic group having 2 to 4 carbon atoms (i.e., C 2~4 Examples of alkenyl groups include ethenyl, propenyl, and butadienyl (including 1,2-butadienyl and 1,3-butadienyl).

[0114] The term "alkynyl" refers to an aliphatic group containing at least one carbon-carbon triple bond (C≡C) and having 2 to 10 carbon atoms (i.e., C 2~10 alkynyl), or an aliphatic group having 2 to 4 carbon atoms (i.e., C 2~4 The term "alkynyl" also includes groups having one triple bond and one double bond.

[0115] The term "alkoxy" refers to the group "-O-alkyl", such as methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, tert-butoxy, sec-butoxy, n-pentoxy, n-hexoxy, and 1,2-dimethylbutoxy. The term "haloalkoxy" refers to an alkoxy group as indicated above in which one or more hydrogen atoms have been replaced with a halogen.

[0116] The term "lower alkyl" refers to 1~4 Exemplary lower alkyl groups are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and tert-butyl.

[0117] The term "lower haloalkyl" refers to a C substituted with one or more halogen atoms. 1~4 It refers to a straight or branched alkyl group.

[0118] The term "heteroatom" means one or more of oxygen, sulfur, nitrogen, phosphorus, or silicon (including any oxidized form of nitrogen, sulfur, phosphorus, or silicon; the quaternized form of any basic nitrogen or substitutable nitrogen of a heterocycle, such as N (as in 3,4-dihydro-2H-pyrrolyl), NH (as in pyrrolidinyl), or NR+ (as in N-substituted pyrrolidinyl)).

[0119] The term "unsaturated," as used herein, means that a moiety has one or more units of unsaturation.

[0120] The term "partially unsaturated" in the context of a ring, unless otherwise defined, refers to a monocyclic ring or a constituent ring in a polycyclic (e.g., bicyclic, tricyclic, etc.) ring system, which contains at least one degree of unsaturation in addition to the degree of unsaturation provided by the ring itself, but is not aromatic. Examples of partially unsaturated rings include, but are not limited to, 3,4-dihydro-2H-pyran, 3-pyrroline, 2-thiazoline, and the like. When a partially unsaturated ring is part of a polycyclic ring system, the other constituent rings in the polycyclic ring system may be saturated, partially unsaturated, or aromatic, but the attachment point of the polycyclic ring system is on the partially unsaturated constituent ring. For example, unless otherwise defined, 1,2,3,4-tetrahydroquinoline is an aromatic ring when its attachment point is through the piperidino ring, e.g., [ka] In the case of , it is a partially unsaturated ring.

[0121] The term "saturated" in the context of a ring, unless otherwise defined, refers to a 3-10 membered monocyclic ring or a 7-14 membered polycyclic (e.g., bicyclic, tricyclic, etc.) ring system in which the monocyclic ring or the constituent ring that is the point of attachment of the polycyclic ring system does not contain any additional degree of unsaturation in addition to that provided by the ring itself. Examples of monocyclic saturated rings include, but are not limited to, azetidine, oxetane, cyclohexane, etc. When a saturated ring is part of a polycyclic ring system, the other constituent rings in the polycyclic ring system may be saturated, partially unsaturated, or aromatic, but the attachment point of the polycyclic ring system is on the saturated constituent ring. For example, unless otherwise defined, 2-azaspiro[3.4]oct-6-ene is an azaspiro[3.4]oct-6-ene when its point of attachment is through the azetidino ring, e.g., [ka] In the case of, it is a saturated ring.

[0122] As used herein, the term "bridged bicyclic" refers to any bicyclic ring system having at least one bridge, i.e., saturated or partially unsaturated carbocyclic or heterocyclic. As defined by IUPAC, a "bridge" is an unbranched chain of atoms or an atom or valence bond connecting two bridgeheads, and a "bridgehead" is any skeletal atom of the ring system that is bonded to three or more skeletal atoms (except hydrogen). In some embodiments, the bridged bicyclic group has 7-12 ring members and 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Such bridged bicyclic groups are well known in the art and include the groups shown below, in which each group is attached to the remainder of the molecule at any substitutable carbon or nitrogen atom, unless otherwise specified, and the bridged bicyclic group may be substituted with one or more of the substituents described for the aliphatic groups. Additionally or alternatively, any substitutable nitrogen of the bridged bicyclic group may be substituted. Exemplary bridged bicyclic groups include: [ka] Examples include:

[0123] The term "acyl" refers to the group -C(=O)R, where R is hydrogen, alkyl, cycloalkyl, heterocyclyl, aryl, heteroalkyl, or heteroaryl, each of which may be optionally substituted as defined herein. Examples of acyl groups include formyl, acetyl, cyclohexylcarbonyl, cyclohexylmethylcarbonyl, benzoyl, and the like.

[0124] The term "amide" refers to the group -C(=O)NR a R b refers to the "C-amide" group and the group -NR a C(=O)R b refers to both the "N-amide" group and the R a and R bis independently selected from the group consisting of hydrogen, alkyl, aryl, haloalkyl, heteroaryl, cycloalkyl, and heterocyclyl, each of which is optionally substituted.

[0125] "Amino" is the group -NR a R b In the formula, R a and R b is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl, heteroaryl, cycloalkyl, and heterocyclyl, each of which may be optionally substituted.

[0126] The term "aryl" refers to an aromatic carbocyclic group having a single ring (e.g., monocyclic) or multiple rings (e.g., bicyclic or tricyclic), including fused systems. As an example, as used herein, aryl refers to a group having 6 to 20 ring carbon atoms (i.e., C 6~20 aryl), 6 to 12 carbon ring atoms (i.e., C 6~12 aryl), etc. Some examples of aryl groups include phenyl, naphthyl, fluorenyl, and anthryl. As used herein, aryl does not encompass or overlap in any way with heteroaryl, as defined below. When one or more aryl groups are fused to a heteroaryl ring, the resulting ring system is a heteroaryl.

[0127] The term "cyano" or a "carbonitrile" group is represented by --CN.

[0128] The term "cycloalkyl" refers to a saturated or partially saturated cyclic alkyl group having a single ring or multiple rings, including fused, bridged, and spiro ring systems. The term "cycloalkyl" also includes cycloalkenyl groups (i.e., cyclic groups having at least one double bond). As used herein, cycloalkyl refers to a cyclic alkyl group having 3 to 20 ring carbon atoms (i.e., C 3~20 cycloalkyl), 3 to 8 ring carbon atoms (i.e., C 3~8 cycloalkyl), or 3 to 5 ring carbon atoms (i.e., C 3~5cycloalkyl), etc. Examples include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0129] The term "bridged" refers to a ring fusion in which non-adjacent atoms on the ring are linked by a divalent substituent, such as an alkylenyl group, an alkylenyl group containing one or two heteroatoms, or a single heteroatom. Examples of bridged ring systems include quinuclidinyl and adamantanyl.

[0130] The term "fused" refers to a ring that is joined to an adjacent ring.

[0131] The term "spiro" refers to a ring substituent that is connected by two bonds at the same carbon atom. Some examples of spiro groups include 1,1-diethylcyclopentane, dimethyl-dioxolane, and 4-benzyl-4-methylpiperidine, where cyclopentane and piperidine are each spiro substituents.

[0132] "Halogen" or "halo" includes fluoro (F), chloro (Cl), bromo (Br), and iodo (I).

[0133] "Deuterium," "D," and "deuterium" all refer to heavy hydrogen.

[0134] "N" may represent a nitrogen atom or a bond containing nitrogen, or -NH, depending on the context. Similarly, "S" may represent a sulfur atom or a bond containing sulfur, and "O" may represent an oxygen atom or a bond containing oxygen.

[0135] "Haloalkyl" includes unbranched or branched alkyl groups as defined above in which one or more hydrogen atoms are replaced with halogen. When a residue is substituted with multiple halogens, the residue may be referred to by using a prefix corresponding to the number of halogen moieties attached. Dihaloalkyl and trihaloalkyl refer to alkyl substituted with two ("di") or three ("tri") halo groups, which may, but are not necessarily, the same halogen. Some examples of haloalkyl include difluoromethyl (-CHF2) and trifluoromethyl (-CF3).

[0136] The term "heteroaryl" refers to an aromatic group having a single ring, multiple rings, or multiple fused rings, with one or more ring heteroatoms independently selected from N, O, and S. As used herein by way of example, heteroaryl refers to an aromatic group having 1 to 20 carbon ring atoms (i.e., C 1~20 Heteroaryl), 3 to 12 carbon ring atoms (C 3~12 As used herein, the number of ring heteroatoms is independently selected from N, O, or S. Examples of heteroaryl groups include pyrimidinyl, purinyl, pyridyl, pyridazinyl, benzothiazolyl, and pyrazolyl. The term "heteroaryl" does not encompass or overlap with "aryl" as defined above.

[0137] The term "heterocyclyl" or "heterocyclic ring" refers to a non-aromatic cyclic alkyl group having at least one ring heteroatom independently selected from boron (B), nitrogen (N), oxygen (O), phosphorus (P) and sulfur. As used herein, "heterocyclyl" or "heterocyclic ring" refers to a saturated or partially saturated ring unless otherwise indicated, for example, in some embodiments, "heterocyclyl" or "heterocyclic ring" refers to a partially saturated ring when specified. "Heterocyclyl" or "heterocyclic ring" includes heterocycloalkenyl groups (i.e., heterocyclyl groups having at least one double bond). Heterocyclyls may be monocyclic or polycyclic, and the multiple rings may be fused, bridged, or spiro. As used herein, heterocyclyl refers to a ring having 2 to 20 carbon ring atoms (i.e., C 2~20 heterocyclyl), 3 to 8 carbon ring atoms (i.e., C 3~8 heterocyclyl), or 3 to 6 carbon ring atoms (i.e., C 3~6Heterocyclyl) having 1 to 5 ring heteroatoms independently selected from B, N, O, P, or S. Examples of heterocyclyl groups include pyrrolidinyl, piperidinyl, piperazinyl, oxetanyl, dioxolanyl, azetidinyl, and morpholinyl. The term "bridged heterocyclyl" refers to a 4-10 membered cyclic moiety connected to one or more (e.g., 1 or 2) 4-10 membered cyclic moieties having at least one heteroatom at two non-adjacent atoms of the heterocyclyl, each heteroatom being independently selected from B, N, O, P, and S. As used herein, "bridged heterocyclyl" includes bicyclic and tricyclic ring systems. Also, as used herein, the term "spiro-heterocyclyl" refers to a ring system in which a 3-10 membered heterocyclyl has one or more additional rings, which one or more additional rings are 3-10 membered cycloalkyl or 3-10 membered heterocyclyl, and a single atom of the one or more additional rings is also an atom of the 3-10 membered heterocyclyl. Also, as used herein, the term "fused heterocyclyl" refers to a 3-10 membered cyclic moiety connected to one or more (e.g., one or two) 3-10 membered cyclic moieties having at least one heteroatom at two adjacent atoms of the heterocyclyl, each heteroatom being independently selected from B, N, O, P, and S. As used herein, "fused heterocyclyl" includes bicyclic and tricyclic ring systems. As used herein, the terms "heterocyclyl" and "heterocyclic ring" are used interchangeably and include monocyclic rings, bridged rings, spirocyclic rings, or fused carbocyclic rings, and combinations thereof. In some embodiments, the heterocyclyl is substituted with an oxo group.

[0138] The term "carbocyclyl" or "carbocyclic ring" refers to a non-aromatic cyclic aliphatic group that does not have any ring heteroatoms, and "carbocyclyl" or "carbocyclic ring" refers to a saturated or partially saturated ring unless otherwise specified, for example, in some embodiments, "carbocyclyl" or "carbocyclic ring" refers to a partially saturated ring, if specified. "Carbocyclyl" or "carbocyclic ring" includes carbocycloalkenyl groups (i.e., carbocyclic groups having at least one double bond). Carbocyclic rings may be monocyclic or polycyclic, which multiple rings may be fused, bridged, or spiro. As used herein, a carbocyclic ring is a ring having 3 to 14 carbon ring atoms (i.e., C 3~14 Carbocyclic ring or C 3~14 Carbocyclic rings), 3 to 8 carbon ring atoms (i.e., C 3~8 carbocyclic ring), or 3 to 6 carbon ring atoms (i.e., C 3~6 Examples of carbocyclic groups include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. The term "bridged carbocyclic ring" refers to a 3- to 10-membered cyclic moiety connected at two non-adjacent carbon atoms of a carbocyclyl to one or more (e.g., one or two) 3- to 10-membered cyclic moieties. As used herein, "bridged carbocyclyl" or "bridged carbocyclic ring" includes bicyclic and tricyclic ring systems. Also, as used herein, the term "spiro-carbocyclyl" or "spiro-carbocyclic ring" includes bicyclic and tricyclic ring systems and refers to a ring system in which a 3- to 10-membered carbocyclyl has one or more additional rings, which one or more additional rings are 3- to 10-membered carbocyclyls, and a single atom of the one or more additional rings is also an atom of the 3- to 10-membered carbocyclyl. Also, as used herein, the term "fused carbocyclyl" or "fused carbocyclic ring" includes bicyclic and tricyclic ring systems and refers to a 3- to 10-membered cyclic moiety linked at two adjacent carbon atoms of a carbocyclyl to one or more (e.g., one or two) 3- to 10-membered cyclic moieties. As used herein, the terms "carbocyclyl" and "carbocyclic ring" are used interchangeably and include monocyclic carbocyclic rings, bridged carbocyclic rings, spiro carbocyclic rings or fused carbocyclic rings and combinations thereof.

[0139] "Hydroxy" or "hydroxyl" refers to the group --OH.

[0140] "Oxo" refers to the group (=O) or (O).

[0141] The term "sulfonyl" refers to the group -S(O)R a In the formula, R a is alkyl, haloalkyl, heterocyclyl, cycloalkyl, heteroaryl, or aryl. Some examples of sulfonyl are methylsulfonyl, ethylsulfonyl, phenylsulfonyl, and toluenesulfonyl.

[0142] Whenever a group terminates in a single-bonded nitrogen atom, the group represents an -NH group unless otherwise indicated. Similarly, unless otherwise indicated, hydrogen atoms are considered implied and present when necessary according to the knowledge of one of ordinary skill in the art to complete valence or provide stability.

[0143] "Optional" or "optionally" or "may" means that the event or circumstance described below may or may not occur, and the description includes the occurrence and non-occurrence of said event or circumstance. Also, the term "optionally substituted" means that any one or more hydrogen atoms on the specified atom or group may or may not be replaced by suitable substituents other than hydrogen. The substituents may be the same or different at each position. Combinations of substituents envisioned by the present invention are preferably those that result in the formation of stable or chemically feasible compounds. The term "stable" as used herein refers to compounds that are substantially unchanged when subjected to conditions that allow for their production, detection, and, in certain embodiments, their recovery, purification, and use for one or more of the purposes disclosed herein.

[0144] "Substituted" means that one or more hydrogen atoms on the specified atom or group are replaced with one or more substituents other than hydrogen, provided that the normal valence of the specified atom is not exceeded. Substituents include, but are not limited to, alkyl, alkenyl, alkynyl, alkoxy, acyl, amino, amido, amidino, aryl, azido, carbamoyl, carboxyl, carboxyl ester, cyano, guanidino, halo, haloalkyl, heteroalkyl, heteroaryl, heterocyclyl, hydroxy, hydrazino, imino, oxo, nitro, alkylsulfinyl, sulfonic acid, alkylsulfonyl, thiocyanate, thiol, thione, or combinations thereof. Similar indefinite structures arrived at by defining a substituent with an infinite number of additional substituents (e.g., substituted aryl with a substituted alkyl, which is itself substituted with a substituted aryl group, which is further substituted with a substituted heteroalkyl group, etc.) are not intended to be encompassed herein. Unless otherwise specified, the maximum number of consecutive substitutions in the compounds described herein is three. For example, the sequential substitution of a substituted aryl group with two other substituted aryl groups is limited to ((substituted aryl)substituted aryl)substituted aryl. Similarly, the above definition is not intended to include impermissible substitution patterns (e.g., a methyl substituted with five fluorines or a heteroaryl group with two adjacent oxygen ring atoms). Such impermissible substitution patterns are well known to those of skill in the art. Whenever used to modify a chemical group, "substituted" may also describe other chemical groups as defined herein. For example, the term "substituted aryl" includes, but is not limited to, "alkylaryl". Unless otherwise specified, when a group is described as being optionally substituted, none of the substituents of that group are themselves substituted.

[0145] In some cases, "substituted alkyl" refers to an alkyl group having one or more substituents including hydroxyl, halo, amino, alkoxy, cycloalkyl, heterocyclyl, aryl, and heteroaryl. In further cases, "substituted cycloalkyl" refers to a cycloalkyl group having one or more substituents including alkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, amino, alkoxy, halo, oxo, and hydroxyl. "Substituted heterocyclyl" refers to a heterocyclyl group having one or more substituents including alkyl, amino, haloalkyl, heterocyclyl, cycloalkyl, aryl, heteroaryl, alkoxy, halo, oxo, and hydroxyl. The term "substituted aryl" refers to an aryl group having one or more substituents including halo, alkyl, amino, haloalkyl, cycloalkyl, heterocyclyl, heteroaryl, alkoxy, and cyano. The term "substituted heteroaryl" refers to a heteroaryl group having one or more substituents including halo, amino, alkyl, haloalkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkoxy, and cyano, and the term "substituted sulfonyl" refers to the group -S(O)R, where R is substituted with one or more substituents including alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl. In other examples, one or more of the substituents may be further substituted with halo, alkyl, haloalkyl, hydroxyl, alkoxy, cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is substituted. In other examples, the substituents may be further substituted with halo, alkyl, haloalkyl, alkoxy, hydroxyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is unsubstituted.

[0146] In some embodiments, substituted cycloalkyl, substituted heterocyclyl, substituted aryl, and / or substituted heteroaryl include cycloalkyl, heterocyclyl, aryl, and / or heteroaryl having a substituent on the atom of the ring at which the cycloalkyl, heterocyclyl, aryl, and / or heteroaryl is bonded to the remainder of the compound. For example, in the moiety below, the phenyl ring is substituted with a meta-chloro group. [ka]

[0147] The compounds disclosed herein or their pharma- ceutically acceptable salts may contain one or more asymmetric centers and therefore may give rise to enantiomers, diastereomers, and other stereoisomeric forms, which may be defined in terms of absolute stereochemistry as (R)- or (S)-, or for amino acids as (D)- or (L)-. The present disclosure includes all such possible isomers, as well as their racemic and optically pure forms. Optically active (+) and (-), (R)- and (S)-, or (D)- and (L)-isomers may be prepared using chiral synthons or chiral reagents, or resolved by conventional techniques such as chromatography and fractional crystallization. Traditional techniques for the preparation and isolation of individual enantiomers include chiral synthesis from suitable optically pure precursors, or resolution of the racemates (or racemates of salts or derivatives) using, for example, chiral high-performance liquid chromatography (HPLC). When compounds disclosed herein contain olefinic double bonds or other geometrically asymmetric centers, unless otherwise specified, these compounds include both E and Z geometric isomers. Likewise, all tautomeric forms are intended to be included. Whenever compounds are represented in their chiral form, it is understood that the embodiment includes, but is not limited to, the specific diastereomer or enantiomerically enriched form. In situations where chirality is not specified, it is understood that the embodiment is intended to include either the specific diastereomerically or enantiomerically enriched form, or racemic or non-racemic mixtures of such compounds. A "non-racemic mixture" is a mixture of stereoisomers in a ratio other than 1:1.

[0148] The term "stereoisomer" refers to compounds that contain the same atoms linked by the same bonds but have different three-dimensional structures that are not interchangeable. The present disclosure contemplates various stereoisomers and mixtures thereof, and includes "enantiomers," which refers to two stereoisomers whose molecules are non-superimposable mirror images of one another.

[0149] The term "enantiomers" refers to a pair of stereoisomers that are non-superimposable mirror images of each other. A 1:1 mixture of a pair of enantiomers is a "racemic" mixture. A mixture of enantiomers in a ratio other than 1:1 is a "non-racemic" mixture.

[0150] The term "diastereomers" refers to stereoisomers that have at least two asymmetric atoms, but which are not mirror-images of each other.

[0151] "Tautomer" refers to a proton shift from one atom of a molecule to another atom of the same molecule. The present disclosure includes tautomers of any compound provided herein.

[0152] As used herein, an "effective amount", "sufficient amount" or "therapeutically effective amount" is an amount of a compound sufficient to produce a beneficial or desired result, including a clinical result. Thus, an effective amount may be sufficient, for example, to reduce, shorten or ameliorate the severity and / or duration of a affliction condition associated with FGFR2 signaling or one or more symptoms thereof, to prevent the progression of a condition or symptom associated with a affliction condition associated with FGFR2 signaling, or to enhance or otherwise improve the prophylactic or therapeutic effect of another therapy. An effective amount also includes an amount of a compound that avoids or substantially attenuates undesirable side effects.

[0153] As used herein and as is well understood in the art, "treatment" is an approach for obtaining beneficial or desired results, including clinical results. Beneficial or desired clinical results may include, but are not limited to, alleviation or amelioration of one or more symptoms or conditions, whether detectable or undetectable, reduction in the extent of a disease or afflicted condition, a stabilized (i.e., not worsening) state of a disease or afflicted condition, prevention of the spread of a disease or afflicted condition, delay or slowing of the progression of a disease or afflicted condition, amelioration or palliation, and amelioration (whether partial or total) of a disease or afflicted condition. "Treatment" may also mean prolonging survival compared to expected survival in the absence of treatment. In some embodiments, treatment may be administered after one or more symptoms have developed. In other embodiments, treatment may be administered in the absence of symptoms. For example, treatment may be administered to a susceptible individual prior to the onset of symptoms (e.g., in light of a history of symptoms and / or in light of genetic or other susceptibility factors). Treatment may be continued after symptoms have resolved, e.g., to prevent or delay their recurrence.

[0154] The phrase "in need of" refers to a need for symptomatic or asymptomatic relief from a condition associated with FGFR2 signaling activity or from a condition that may otherwise be alleviated by the compounds and / or compositions of the disclosure.

[0155] Some compounds disclosed herein exist as tautomers. Tautomers are in equilibrium with each other. For example, an amide-containing compound may exist in equilibrium with an imidic acid tautomer. Regardless of which tautomer is shown, and regardless of the nature of the equilibrium between the tautomers, it is understood by those skilled in the art that the compound includes both the amide and imidic acid tautomers. Thus, amide-containing compounds are understood to include their imidic acid tautomers. Similarly, imidic acid-containing compounds are understood to include their amide tautomers.

[0156] The interaction of a solvent and a compound forms a “solvate.” As used herein, solvates also include solvates of the salts of the disclosed compounds and hydrates of the compounds provided herein.

[0157] Any formula or structure provided herein also represents unlabeled and isotopically labeled forms of the compound. Isotopically labeled compounds have the same structure as shown by the formulas provided herein, except that one or more atoms are replaced by an atom having a selected atomic mass or mass number. Examples of isotopes include carbon ( 11 C. 13 C. 14 C), nitrogen ( 15 N), oxygen ( 17 O. 18 O), Phosphorus ( 31 P, 32 P), fluorine ( 18 F), Chlorine ( 36 Cl), and iodine ( 125 Isotopically labeled compounds may be used in metabolic studies, reaction kinetic studies, detection or imaging techniques, such as positron emission tomography (PET) or single photon emission computed tomography (SPECT), in drug or substrate tissue distribution assays, or in radiotherapy of patients.

[0158] In many cases, the compounds disclosed herein are capable of forming acid salts due to the presence of amino and / or groups similar thereto.

[0159] The term "pharmaceutical acceptable salt" refers to a salt prepared from a pharmaceutical non-toxic acid. If the compound of the present invention is basic, its corresponding salt can be conveniently prepared from a pharmaceutical non-toxic acid, including inorganic and organic acids. Since the compounds of formula I, II, III, IV, V, VI, VII, II, or I-II are intended for pharmaceutical use, they are preferably provided in substantially pure form, for example at least 60% pure, more suitably at least 75% pure, especially at least 98% pure (% being weight to weight).

[0160] The pharmaceutical compositions of the present invention comprise a compound represented by formula I, II, III, IV, V, VI, VII, II or I-II or a pharma- ceutically acceptable salt thereof as an active ingredient, a pharma- ceutically acceptable carrier, and optionally other therapeutic ingredients or adjuvants. The compositions include compositions suitable for oral, rectal, topical, and parenteral (including subcutaneous, intramuscular, and intravenous) administration, although the most suitable route in any given case will depend on the particular host and the nature and severity of the condition for which the active ingredient is being administered. The pharmaceutical compositions are conveniently presented in unit dosage form and may be prepared by any of the methods well known in the art of pharmacy.

[0161] In practice, the compound represented by formula I, II, III, IV, V, VI, VII, II or I-II of the present invention, or a prodrug or metabolite or pharma- ceutically acceptable salt thereof, can be combined as an active ingredient in intimate admixture with a pharmaceutical carrier according to conventional pharmaceutical compounding techniques. The carrier may take a wide variety of forms depending on the form of preparation desired for administration, e.g., oral or parenteral (including intravenous) administration. Thus, the pharmaceutical composition of the present invention can be provided as discrete units suitable for oral administration, such as capsules, cachets or tablets, each containing a predetermined amount of the active ingredient. Furthermore, the composition can be presented as a powder, as granules, as a solution, as a suspension in an aqueous liquid, as a non-aqueous liquid, as an oil-in-water emulsion, or as a water-in-oil liquid emulsion. In addition to the common dosage forms described above, the compound represented by formula I, II, III, IV, V, VI, VII, II or I-II, or a pharma- ceutically acceptable salt thereof, can also be administered by controlled release means and / or delivery devices. The composition can be prepared by any of the methods of pharmacy. In general, such methods include the step of bringing the active ingredient into association with the carrier which constitutes one or more necessary ingredients. In general, the compositions are prepared by uniformly and intimately mixing the active ingredient with a liquid carrier or finely divided solid carrier or both. The product can then be conveniently shaped into the desired presentation.

[0162] Thus, the pharmaceutical compositions of the present invention may comprise a pharma- ceutically acceptable carrier and a compound of Formula I, II, III, IV, V, VI, VII, II or I-II, or a pharma- ceutically acceptable salt thereof. The compound of Formula I, II, III, IV, V, VI, VII, II or I-II, or a pharma- ceutically acceptable salt thereof, may be included in the pharmaceutical composition in combination with one or more other therapeutically active compounds.

[0163] The pharmaceutical carriers used may be, for example, solid, liquid or gas. Examples of solid carriers include lactose, terra alba, sucrose, talc, gelatin, agar, pectin, gum arabic (acacia), magnesium stearate, and stearic acid. Examples of liquid carriers are sugar syrup, peanut oil, olive oil, and water. Examples of gaseous carriers include carbon dioxide and nitrogen. In preparing compositions for oral dosage forms, any convenient pharmaceutical medium may be used. For example, water, glycols, oils, alcohols, flavoring agents, preservatives, coloring agents, and the like may be used to form oral liquid preparations such as suspensions, elixirs, and solutions, and carriers such as starch, sugar, microcrystalline cellulose, diluents, granulating agents, lubricants, binders, disintegrating agents, and the like may be used to form oral solid preparations such as powders, capsules, and tablets. Because of their ease of administration, tablets and capsules are the preferred oral dosage units, and solid pharmaceutical carriers are used for these. Optionally, tablets may be coated by standard aqueous or nonaqueous techniques.

[0164] Tablets containing the compositions of the present invention may be prepared by compression or molding, optionally with one or more accessory ingredients or adjuvants. Compressed tablets may be prepared by compressing in a suitable machine the active ingredient in a free-flowing form, such as a powder or granules, optionally mixed with a binder, lubricant, inert diluent, surfactant or dispersing agent. Molded tablets (molded tablets) may be made by molding in a suitable machine a mixture of the powdered compound moistened with an inert liquid diluent. Each tablet preferably contains from about 0.05 mg to about 5 g of the active ingredient, and each cachet or capsule preferably contains from about 0.05 mg to about 5 g of the active ingredient. For example, a formulation intended for oral administration to humans may contain from about 0.5 mg to about 5 g of the active agent compounded with an appropriate and convenient amount of carrier material, which may vary from about 0.05 to about 95 percent of the total composition. A unit dosage form usually contains from about 0.01 mg to about 2 g of the active ingredient.

[0165] The pharmaceutical composition of the present invention suitable for parenteral administration may be prepared as a solution or suspension of the active compound in water.For example, a suitable surfactant such as hydroxypropylcellulose may be included.Dispersions may also be prepared in glycerol, liquid polyethylene glycols, and mixtures thereof in oil.Furthermore, a preservative may be included to prevent the harmful growth of microorganisms.

[0166] The pharmaceutical compositions of the present invention suitable for injectable use include sterile aqueous solutions or dispersions. Moreover, the compositions can be in the form of sterile powders for the extemporaneous preparation of such sterile injectable solutions or dispersions. In all cases, the final injectable form must be sterile and effectively fluid for easy syringability. The pharmaceutical compositions must be stable under the conditions of manufacture and storage. Thus, they should preferably be preserved against the contaminating action of microorganisms such as bacteria and fungi. The carrier can be, for example, a solvent or dispersion medium containing water, ethanol, a polyol (e.g., glycerol, propylene glycol and liquid polyethylene glycol), vegetable oils, and suitable mixtures thereof.

[0167] The pharmaceutical composition of the present invention may be in a form suitable for topical use, such as, for example, an aerosol, cream, ointment, lotion, dusting powder, etc. Additionally, the composition may be in a form suitable for use in a transdermal device. These formulations may be prepared utilizing the compound represented by formula I of the present invention or a pharma- ceutically acceptable salt thereof by conventional processing methods. For example, a cream or ointment is prepared by mixing a hydrophilic material and water with about 0.05% to about 10% by weight of the compound to produce a cream or ointment having a desired consistency.

[0168] The pharmaceutical composition of the present invention may be in a form suitable for rectal administration, where the carrier is a solid. Preferably, the mixture forms unit-dose suppositories. Suitable carriers include cocoa butter and other materials commonly used in the art. Suppositories may be conveniently formed by first mixing the composition with the softened or melted carrier(s), followed by cooling and shaping in molds.

[0169] In addition to the above-mentioned carrier components, the above-mentioned pharmaceutical formulations may optionally contain one or more additional carrier components such as diluents, buffers, flavoring agents, binders, surfactants, thickeners, lubricants, preservatives (including antioxidants), etc. Furthermore, other adjuvants may be included to make the formulation isotonic with the blood of the intended recipient. The compositions containing the compound described by formula I or its pharma-ceutically acceptable salts may also be prepared in powder or liquid concentrate form.

[0170] Generally, dosage levels on the order of about 0.001 mg / kg to about 150 mg / kg body weight / day, or alternatively about 0.05 mg to about 7 g / patient / day, are useful in treating the above conditions. For example, cancer, immune system diseases and conditions may be effectively treated by administration of about 0.001 to 50 mg of compound / kg body weight / day, or alternatively about 0.05 mg to about 3.5 g / patient / day.

[0171] However, it will be understood that the specific dose level for any particular patient will depend on a variety of factors, including age, body weight, general health, sex, diet, time of administration, route of administration, rate of excretion, drug combination, and the severity of the particular disease being treated.

[0172] The term "disease" refers to any disease, ailment, illness, symptom or indication, and may be interchangeable with the terms "disorder" or "condition."

[0173] The term "cancer" encompasses all forms of cancer, including, but not limited to, all forms of carcinoma, melanoma, blastoma, sarcoma, lymphoma, and leukemia. Examples include, but are not limited to, breast cancer, bladder cancer, bladder carcinoma, uterine cancer, brain cancer, cervical cancer, colorectal cancer, esophageal cancer, endometrial cancer, liver cancer (including HCC), laryngeal cancer, lung cancer, osteosarcoma, ovarian cancer, pancreatic cancer, prostate cancer, renal carcinoma, kidney cancer (including RCC), thyroid cancer, acute lymphocytic leukemia, acute myeloid leukemia, ependymoma, Ewing's sarcoma, glioblastoma, medulloblastoma, neuroblastoma, osteosarcoma, rhabdoid cancer, and nephroblastoma (Wilm's tumor).

[0174] In some such embodiments, the compounds detailed herein or pharma- ceutically acceptable salts, prodrugs, metabolites, or derivatives thereof may also be used in combination with additional therapies, which may optionally include one or more therapeutic agents, radiation therapy, surgery (e.g., lumpectomy and mastectomy), chemotherapy, gene therapy, DNA therapy, viral therapy, RNA therapy, immunotherapy, bone marrow transplantation, nanotherapy, monoclonal antibody therapy, or combinations of the above.

[0175] General reaction scheme The compounds of the present invention may be synthesized by a variety of methods by those skilled in the art of organic chemistry, and general synthetic schemes for preparing the compounds of the present invention are described herein. These schemes are illustrative and do not limit the possible ways that a person skilled in the art can prepare the compounds disclosed herein. Different methods for preparing the compounds disclosed herein will be apparent to those skilled in the art. General schemes for preparing the compounds of the present invention are given in the Examples section described below. Preparation of homochiral examples may be achieved by techniques known to those skilled in the art. For example, homochiral compounds may be prepared by separation of racemic products or diastereomers by chiral phase preparative HPLC. Alternatively, the example compounds may be prepared by methods known to give enantiomerically or diastereomerically enriched products.

[0176] The reactions and techniques disclosed below in this section are carried out in solvents appropriate to the reagents and materials used and suitable for the transformations carried out. It should also be understood that all proposed reaction conditions, including the choice of solvent, reaction atmosphere, reaction temperature, duration of the experiment and work-up procedures, are selected to be standard conditions for the reaction, which should be readily recognized by those skilled in the art. It is also understood by those skilled in the art of organic synthesis that the functional groups present on the various parts of the molecule must be compatible with the reagents and reactions selected. The limitations of the substituents that are compatible with the reaction conditions will be apparent to those skilled in the art, and alternative methods are required when incompatible substituents are present. In some cases, judgment is required to change the order of synthetic steps or to select one particular route over another to obtain the desired compounds of the invention. It will also be understood that the planning of any synthetic route in this field includes the judicious selection of protecting groups (Wuts and Greene, Greene's Protective Groups in Organic Synthesis, Fourth Edition, Wiley and Sons (2007)) used to protect reactive functional groups present in the compounds described in this invention.

[0177] The disclosed compounds of the invention may be prepared from commercially available reagents using the synthetic methods and reaction schemes described herein, or using other reagents and conventional methods well known to those skilled in the art. For example, the compounds of the invention may be prepared using general reaction schemes I or II, followed by a deprotection step to remove the protecting groups to obtain the disclosed compounds.

[0178] In some embodiments, compounds of formula (II) are prepared according to the general procedure depicted in Scheme I below. [ka]

[0179] In some embodiments, step 8 comprises reacting a compound of formula 10 with a BL functionalized with a suitable reactive group. b -R b to form a compound of formula 12. In some embodiments, the suitable reactive group is a boronic ester. In some embodiments, the suitable reactive group is a pinacol boronic ester.

[0180] In some embodiments, step 9 comprises bromination of the compound of formula 12. In some embodiments, the reagent used is N-bromosuccinimide.

[0181] In some embodiments, step 10 comprises reacting a compound of formula 13 with a DL functionalized with a suitable reactive group. d -R d to form a compound of formula II. In some embodiments, the suitable reactive group is a boronic ester or a boronic acid.

[0182] In some embodiments, compounds of formula (IV) are prepared according to the general procedure depicted in Scheme II below. [ka]

[0183] Step 1: 3-Bromo-2-methoxypyridin-4-amine To a solution of 2-methoxypyridin-4-amine (commercially available compound B1, 500.0 g, 4.0 mol, 1.0 equiv.) in ACN (5.0 L, 10.0 V) at 10° C. was added NBS (783.1 g, 4.4 mol, 1.1 equiv.) in one portion, and the mixture was warmed to 20° C. and stirred for 1 h. The reaction mixture was poured into H2O (7.5 L, 15.0 V) and MTBE (5.0 L, 10.0 V) and then separated. The aqueous phase was extracted with MTBE (5.0 L, 10.0 V) and the combined organic phase was washed with 10 wt % aqueous NaCl (5.0 L, 10.0 V), dried over Na2SO4, and concentrated. The crude product was purified by silica gel chromatography eluting with heptane / EtOAc=10 / 1 (2.5 L, 5.0 V) to give 3-bromo-2-methoxypyridin-4-amine (706.7 g, 93% assay, 81% yield) as a brown solid. 1 H NMR (400MHz, DMSO-d6) δ 7.60 (d, J = 5.6 Hz, 1H), 6.37 (d, J = 5.6 Hz, 1H), 6.20 (s, 2H), 3.81 (s, 3H).

[0184] Step 2: 3-Bromo-5-iodo-2-methoxypyridin-4-amine To a solution of 3-bromo-2-methoxypyridin-4-amine (706.7 g, 93% assay, 3.3 mol, 1.0 equiv) in ACN (7.1 L, 10 V) was added HOAc (19.8 g, 0.33 mol, 0.1 equiv) and NIS (1124.9 g, 5.0 mol, 1.5 equiv) at 0° C., and the mixture was warmed to 20° C. and stirred for 2 h. HO (35.5 L, 50 V) was added slowly to the mixture during which a solid precipitated. The mixture was stirred for 30 min and filtered. The filter cake was washed with HO (2 V), collected and dried to give 3-bromo-5-iodo-2-methoxypyridin-4-amine (918.7 g, 94% assay, 81% yield) as a pink solid. 1 H NMR (400MHz, DMSO-d6) δ 8.05 (s, 1H), 6.08 (s, 2H), 3.82 (s, 3H).

[0185] Step 3: 4-Amino-5-bromo-6-methoxynicotinonitrile To a solution of 3-bromo-5-iodo-2-methoxypyridin-4-amine (410.0 g, 94% assay, 1.2 mol, 1.0 equiv) in DMF (4.1 L, 10 V) was added Zn(CN)2 (82.2 g, 0.7 mol, 0.55 equiv), Pd(dba)3 (91.6 g, 0.1 mol, 0.1 equiv) and dppf (110.9 g, 0.2 mol, 0.2 equiv) under N2 at 25 °C. The mixture was heated to 80 °C and stirred for 2 h. H2O (20.5 L, 50 V) was added slowly to the mixture during which a solid precipitated. The mixture was filtered and the filter cake was washed with H2O (0.8 L, 2 V). The filter cake was dissolved in DCM (8.2 L, 20 V), washed with 10 wt% aqueous EDTA (4.1 L, 10 V) and 10 wt% aqueous NaCl (4.1 L, 10 V), dried over Na2SO4, and concentrated. The two batches (410.0 g x 2) were combined and the crude product was purified by silica gel chromatography eluting with heptane / EtOAc = 5 / 1 to give 4-amino-5-bromo-6-methoxynicotinonitrile (342.9 g, 93% assay, 59% yield) as a yellow solid. 1 H NMR (300MHz, DMSO-d6) δ 8.22 (s, 1H), 6.95 (s, 2H), 3.91 (s, 3H).

[0186] Step 4: (E)-4-Amino-5-(2-ethoxyvinyl)-6-methoxynicotinonitrile To a solution of 4-amino-5-bromo-6-methoxynicotinonitrile (342.9 g, 93% assay, 1.4 mol, 1.0 equiv) in 1,4-dioxane (5.1 L, 15 V) was added HO (0.3 L, 1 V), 4-amino-5-bromo-6-methoxynicotinonitrile (554.6 g, 2.8 mol, 2.0 equiv), SPhos (41.1 g, 0.1 mol, 0.075 equiv), KCO (386.4 g, 2.8 mmol, 2.0 equiv) and Pd(OAc) (9.0 g, 0.04 mol, 0.03 equiv) under N at 25 °C and the mixture was warmed to 80 °C and stirred for 16 h. The mixture was cooled to 25° C., then EA (6.9 L, 20 V) and H2O (6.9 L, 20 V) were added. The mixture was separated and the aqueous layer was extracted with EA (3.5 L, 10 V). The combined organic layers were washed with 10 wt % aqueous NaCl (6.9 L, 20 V), dried over Na2SO4 and concentrated. The residue was purified by silica gel chromatography eluting with heptane / EtOAc = 5 / 1 to give (E)-4-amino-5-(2-ethoxyvinyl)-6-methoxynicotinonitrile (278.6 g, 97% assay, 89% yield) as a yellow solid. 1 H NMR(400MHz,DMSO-d6) δ 8.03(s,1H),7.15(d,J=12.7Hz,1H),6.46(s,2H),5.57(d,J=12.7Hz,1H),3.96-3.88(m,2H),3.86(s,3H),1.25(t,J=7.0Hz,3H).

[0187] Step 5: 4-Methoxy-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile A solution of (E)-4-amino-5-(2-ethoxyvinyl)-6-methoxynicotinonitrile (200.0 g, 97% assay, 885.8 mmol, 1.0 equiv) in AcOH (2.0 L, 10.0 V) was warmed to 100° C. and stirred for 3 h. The reaction mixture was concentrated and MTBE (2.0 L, 10.0 V) was added to the residue. The mixture was stirred for 30 min and filtered. The filter cake was collected and dried at 50° C. to give 4-methoxy-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile (151.2 g, 95% purity, 93% assay, 92% yield) as a pale pink solid.1 H NMR (400MHz, DMSO-d6) δ 12.46(s,1H),8.31(s,1H),7.47(d,J=13.5Hz,1H),6.64(s,1H),4.05(s,3H).

[0188] Step 6: 4-Hydroxy-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile To a solution of 4-methoxy-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile (150.0 g, 93% assay, 803.8 mmol, 1.0 equiv.) in ACN (1.5 L, 10.0 V), iodotrimethylsilane (160.8 g, 803.8 mmol, 1.0 equiv.) was added at 25° C., and the mixture was warmed to 80° C. and stirred for 2 h. The reaction mixture was concentrated and heptane (1.5 L, 10.0 V) was added to the residue. The mixture was concentrated again and MTBE / heptane=1 / 1 (750.0 mL, 5.0 V) was added. The mixture was stirred for 30 min and filtered. The filter cake was collected and dried to give 4-hydroxy-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile (120.5 g, 97% purity, 92% assay, 86% yield) as a yellow solid. 1 H NMR (400MHz, DMSO-d6) δ 12.15(s,1H),11.61(s,1H),7.90(d,J=20.6Hz,1H),7.19-7.05(m,1H),6.55(dd,J=3.0,2.0Hz,1H).

[0189] Step 7: 4-Chloro-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile To a solution of 4-hydroxy-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile (100.0 g, 92% assay, 576.2 mmol, 1.0 equiv) in ACN (0.3 L, 3 V) was added POCl3 (265.0 g, 1728.6 mmol, 3.0 equiv) at 25 °C, and the mixture was heated to 80 °C and stirred for 4 h. The reaction mixture was cooled to 20 °C and slowly poured into H2O (2.0 L, 20 V). Then the mixture was adjusted to PH = 7-8 with 5 wt% aqueous NaHCO3. The mixture was extracted with EA (1.5 L x 2, 15 V x 2), and the combined organic layers were washed with 10% aqueous NaCl (1.0 L, 10 V), dried over Na2SO4, and concentrated. The residue was triturated with heptane (0.5 L, 5 V) to give 4-chloro-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile (105.4 g, 93% purity, 79% assay, 81% yield) as a brown solid. 1 H NMR (400MHz, DMSO-d6) δ 12.97 (s, 1H), 8.53 (s, 1H), 7.79-7.64 (m, 1H), 6.81-6.68 (m, 1H).

[0190] Step 8: 3-Bromo-4-chloro-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile To a solution of 4-chloro-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile (50.0 g, 79% assay, 221.0 mmol, 1.0 equiv.) in DMF (350.0 mL, 7.0 V) at 0° C. was added NBS (39.3 g, 221.0 mmol, 1.0 equiv.) and the mixture was stirred at 0° C. for 4 h. The mixture was poured into HO (1050.0 mL, 35.0 V), during which a solid precipitated. The mixture was filtered and the filter cake was triturated with MTBE (250.0 mL, 5 V) for 2 h. The mixture was filtered and the filter cake was collected and dried to give 3-bromo-4-chloro-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile (50.1 g, 98% purity, 96% assay, 85% yield) as a yellow solid. 1 H NMR (400MHz, DMSO-d6) δ 13.36 (s, 1H), 8.58 (s, 1H), 7.97 (d, J = 9.0Hz, 1H).

[0191] Step 9: 3-Bromo-4-chloro-1-methyl-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile To a solution of 3-bromo-4-chloro-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile (45.0 g, 96% assay, 169.1 mmol, 1.0 equiv) in DMF (450.0 mL, 10.0 V) was added K2CO3 (46.7 g, 338.2 mmol, 2.0 equiv) and MeI (48.0 g, 338.2 mmol, 2.0 equiv) at 0 °C and the reaction mixture was heated to 25 °C and stirred for 3 h. The mixture was poured into HO (1.8 L, 40.0 V), during which time a solid precipitated. The mixture was filtered and the filter cake was collected and dried to give 3-bromo-4-chloro-1-methyl-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile (42.5 g, 98% purity, 97% assay, 90% yield) as an off-white solid. 1 H NMR (300MHz, DMSO-d6) δ 8.56 (d, J = 7.3 Hz, 1H), 7.97 (s, 1H), 4.07 (s, 3H).

[0192] Step 10: 4-Amino-3-bromo-1-methyl-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile To a solution of 3-bromo-4-chloro-1-methyl-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile (40.0 g, 97% assay, 143.6 mmol, 1.0 equiv) in 1,4-dioxane (200.0 mL, 5.0 V) was added aqueous ammonia (200.0 mL, 5.0 V) at 25° C., and the reaction mixture was warmed to 100° C. and stirred in a closed system for 16 h. The reaction mixture was concentrated and the residue was triturated with HO (400.0 mL, 10 V) for 30 min. The mixture was filtered and the filter cake was triturated with MTBE (200.0 mL, 5 V) for 2 h. The mixture was filtered and the filter cake was collected and dried to give 4-amino-3-bromo-1-methyl-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile (30.8 g, 98% purity, 97% assay, 83% yield) as a yellow solid. 1H NMR (300MHz, DMSO-d6) δ 8.11 (s, 1H), 7.51 (s, 1H), 6.91 (s, 2H), 3.92 (s, 3H).

[0193] Step 11: 4-Amino-3-bromo-2-iodo-1-methyl-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile To a solution of 4-amino-3-bromo-1-methyl-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile (25 g, 97% assay, 96.3 mmol, 1.0 equiv.) in DMF (250.0 mL, 10.0 V), p-toluenesulfonic acid monohydrate (1.8 g, 9.6 mmol, 0.1 equiv.) and NIS (32.1 g, 142.7 mmol, 1.5 equiv.) were added at 0° C., and the reaction mixture was stirred at 0° C. for 3 h. The mixture was poured into HO (1.0 L, 40.0 V), during which time a solid precipitated. The mixture was filtered, and the filter cake was triturated with MTBE (250.0 mL, 10 V) for 4 h. The mixture was filtered and the filter cake was collected and dried to give 4-amino-3-bromo-2-iodo-1-methyl-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile (28.0 g, 98% purity, 92% assay, 71% yield) as a white solid. 1 H NMR (300MHz, DMSO-d6) δ 8.08 (s, 1H), 6.99 (s, 2H), 3.97 (d, J = 4.6Hz, 3H).

[0194] Step 12: Preparation of B15 Step 12 is the reaction of a compound of B13 with a BL functionalized with a suitable reactive group. b -R b to form a compound of formula B15.

[0195] In some embodiments, a suitable reactive group is a boronic ester. In some embodiments, a suitable reactive group is a pinacol boronic ester.

[0196] Step 13: Preparation of Formula IV Step 13 is the reaction of B15 with DL functionalized with a suitable reactive group.d -R d to form a compound of formula IV.

[0197] In some embodiments, the suitable reactive group is a boronic ester or a boronic acid.

[0198] Other compounds of formula (I) of the present invention can be prepared by reference to Scheme I and / or Scheme II. EXAMPLES

[0199] The examples provided herein describe the synthesis of the compounds disclosed herein and the intermediates used to prepare the compounds.It should be understood that the individual steps described herein may be combined.It should also be understood that separate batches of compounds may be combined and then carried forward to the next synthesis step.

[0200] In the following description of the examples, specific embodiments are described. These embodiments are described in sufficient detail to allow those skilled in the art to carry out specific embodiments of the present disclosure. Other embodiments may be utilized, and logical and other changes may be made without departing from the scope of the present disclosure. Therefore, the following description is not intended to limit the scope of the present disclosure, but rather, the scope of the present disclosure is defined by the claims attached hereto.

[0201] [Table 1(1)] [Table 1(2)]

[0202] Example 1 N-(4-(4-amino-5-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide ("Compound 1") [ka] Step 1: 3-Bromo-1H-pyrazole-5-carboxylic acid A round bottom flask was charged with 3-bromo-5-methyl-1H-pyrazole (2.5 g, 15.5 mmol), KMnO4 (4.9 g, 30.1 mmol), H2O (100 mL) and a stir bar. The reaction mixture was stirred at 95 °C for 6 h. The reaction mixture was cooled to room temperature and then filtered. The filtrate was collected and extracted three times with EA (50 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material obtained was purified by silica gel chromatography. Concentration under reduced pressure gave 3-bromo-1H-pyrazole-5-carboxylic acid (2.30 g, 78%) as a white solid. MS (ESI): mass calculated for C4H3BrN2O2: 190; m / z found 191 [M+1] + . 1 H NMR (400MHz, DMSO) δ 14.15 (s, 1H), 13.59 (s, 1H), 6.87 (s, 1H).

[0203] Step 2: Methyl 3-bromo-1H-pyrazole-5-carboxylate A round bottom flask was charged with 3-bromo-1H-pyrazole-5-carboxylic acid (2.3 g, 12 mmol), MeOH (20 mL) and a stir bar. The reaction mixture was cooled to 0° C. and SOCl2 (1.56 g, 13.2 mmol) was added dropwise. The reaction mixture was then stirred at 60° C. for 2 h. The reaction mixture was cooled to room temperature and poured into ice water. The aqueous phase was extracted three times with EA (20 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material obtained was purified by silica gel chromatography. Concentration under reduced pressure afforded methyl 3-bromo-1H-pyrazole-5-carboxylate (2.20 g, 93%) as a white solid. MS (ESI): mass calculated for C5H5BrN2O2: 204; m / z found 205 [M+1] + . 1H NMR (400MHz, DMSO) δ 14.36 (s, 1H), 6.97 (s, 1H), 3.85 (s, 3H).

[0204] Step 3: Methyl 1-amino-3-bromo-1H-pyrazole-5-carboxylate A round-bottom flask was charged with methyl 3-bromo-1H-pyrazole-5-carboxylate (2.2 g, 10.7 mmol), NMP (10 ml) and a stir bar. A solution of t-BuOK (1.32 g, 11.8 mmol) in NMP (5 mL) was added and the mixture was then stirred at 20° C. for 20 min. A solution of O-(4-nitrobenzoyl)hydroxylamine (2.15 g, 11.8 mmol) was added and the reaction mixture was stirred below 25° C. for 2 h. The reaction mixture was diluted with 10% aqueous NaCl (25 mL) and EA (25 mL). The aqueous phase was extracted three times with EA (25 mL). The combined organic layers were washed three times with 5% NaHCO3 (15 mL), H2O (15 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material obtained was purified by silica gel chromatography (EA:PE=17:83). Concentration under reduced pressure gave methyl 1-amino-3-bromo-1H-pyrazole-5-carboxylate (2.00 g, 84%) as a white solid. MS (ESI): mass calculated for C5H6BrN3O2: 219; m / z found 220 [M+1] + . 1 H NMR (400MHz, DMSO) δ 6.96 (s, 2H), 6.89 (s, 1H), 3.83 (s, 3H).

[0205] Step 4: 6-Bromopyrazolo[5,1-f][1,2,4]triazin-4(3H)-one A round bottom flask was charged with methyl 1-amino-3-bromo-1H-pyrazole-5-carboxylate (2.00 g, 9.1 mmol), methanamide (5.0 mL) and a stir bar. The reaction mixture was irradiated in a microwave at 150° C. for 2 h. The reaction mixture was cooled to room temperature and poured into water. The aqueous phase was extracted three times with EA (20 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material obtained was purified by silica gel chromatography. Concentration under reduced pressure gave 6-bromopyrazolo[5,1-f][1,2,4]triazin-4(3H)-one (1.00 g, 51%) as a white solid. MS (ESI): mass calculated for C5H3BrN4O: 214; m / z found 215 [M+1] + . 1 H NMR (400MHz, DMSO) δ 12.58 (s, 1H), 8.12 (s, 1H), 7.24 (s, 1H).

[0206] Step 5: 6-Bromopyrazolo[5,1-f][1,2,4]triazine-4(3H)-thione A round bottom flask was charged with 6-bromopyrazolo[5,1-f][1,2,4]triazine-4(3H)-one (100 mg, 0.46 mmol), Lawesson's reagent (93 mg, 0.23 mmol), toluene (5 mL) and a stir bar. The reaction mixture was stirred at 100° C. for 2 h. The reaction mixture was then cooled to room temperature. The reaction mixture was concentrated under reduced pressure to give the crude product. The crude product was purified by pre-TLC (PE:EA=1:1) to give 6-bromopyrazolo[5,1-f][1,2,4]triazine-4(3H)-thione (80 mg, 74%) as a yellow solid. MS (ESI): mass calculated for C5H3BrN4S: 230; m / z found 231 [M+1] + .

[0207] Step 6: 6-Bromo-4-(methylthio)pyrazolo[5,1-f][1,2,4]triazine A round bottom flask was charged with 6-bromopyrazolo[5,1-f][1,2,4]triazine-4(3H)-thione (80 mg, 0.38 mmol), K2CO3 (53 mg, 0.38 mmol), CHI (60 mg, 0.42 mmol) and DMF (3 mL). The reaction mixture was stirred at room temperature for 2 h. The reaction mixture was poured into water (15 mL). The aqueous layer was extracted three times with DCM (10 mL). The combined organic layers were concentrated under reduced pressure to give 6-bromo-4-(methylthio)pyrazolo[5,1-f][1,2,4]triazine (60 mg, 71%) as a white solid. MS (ESI): mass calculated for CH5BrN4S: 244; m / z found 245 [M+1] + . 1 H NMR (400MHz, DMSO) δ 8.69 (s, 1H), 7.37 (s, 1H), 2.72 (s, 1H).

[0208] Step 7: 6-Bromopyrazolo[5,1-f][1,2,4]triazin-4-mine A round bottom flask was charged with 6-bromo-4-(methylthio)pyrazolo[5,1-f][1,2,4]triazine (60 mg, 0.24 mmol) and NH3-CH3OH (3 mL). The reaction mixture was stirred in a 50 mL autoclave at 100° C. under 50 psi for 12 h. The solvent was evaporated under reduced pressure to give crude 6-bromopyrazolo[5,1-f][1,2,4]triazin-4-amine (50 mg) as a yellow solid. MS (ESI): mass calculated for C5H4BrN5: 213; m / z found 214 [M+1] + .

[0209] Step 8: tert-Butyl (4-(4-aminopyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)carbamate A round bottom flask was charged with 6-bromopyrazolo[5,1-f][1,2,4]triazin-4-amine (30 mg, 0.14 mmol), XPhos-Pd-G2 (11 mg, 0.014 mmol), K3PO4 (60 mg, 0.28 mmol), tert-butyl (4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamate (38 mg, 0.15 mmol), dioxane (5 mL), HO (1 mL) and a stir bar. The reaction mixture was stirred at 100 °C under N2 for 3 h. The reaction mixture was cooled to room temperature. The reaction mixture was extracted three times with EtOAc (15 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure.

[0210] The resulting crude material was purified by pre-TLC (PE:EA=3:1). Concentration under reduced pressure gave tert-butyl (4-(4-aminopyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)carbamate (20 mg, 50%) as a yellow solid. MS(ESI):C 16 H 18 Calculated mass for N6O2: 326; observed m / z 327 [M+1] + .

[0211] Step 9: tert-Butyl (4-(4-amino-5-bromopyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)carbamate A round bottom flask was charged with tert-butyl (4-(4-aminopyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)carbamate (10 mg, 0.03 mmol), NBS (5 mg, 0.03 mmol), ACN (3 mL) and a stir bar. The reaction mixture was stirred at room temperature for 10 minutes. The reaction mixture was poured into water and filtered. The filter cake was collected to give tert-butyl (4-(4-amino-5-bromopyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)carbamate (10 mg, 80%) as a white solid. MS(ESI): C 16 H 17Calculated mass for BrN6O2: 404; observed m / z 405 [M+1] + .

[0212] Step 10: tert-butyl (4-(4-amino-5-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1f][1,2,4]triazin-6-yl)phenyl)carbamate A round-bottom flask was charged with tert-butyl (4-(4-amino-5-bromopyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)carbamate (20 mg, 0.05 mmol), 2-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)-4-methylpyrimidine (19 mg, 0.055 mmol), Pd(PPh3)4 (0.6 mg, 0.005 mmol), K2CO3 (14 mg, 0.1 mmol), dioxane (5 mL), HO (1 mL) and a stir bar under N2. The reaction mixture was stirred at 100 °C under N2 for 3 h. The reaction mixture was cooled to room temperature and poured into water (15 mL). The aqueous layer was extracted three times with EA (5 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude was purified by pre-TLC (PE:EA=1:1) to give tert-butyl (4-(4-amino-5-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1f][1,2,4]triazin-6-yl)phenyl)carbamate (22 mg, 82%) as a white solid. MS(ESI):C 28 H 28 Calculated mass for N8O4: 540; measured m / z: 541 [M+1] + .

[0213] Step 11: 6-(4-aminophenyl)-5-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-4-amine A round bottom flask was charged with tert-butyl (4-(4-amino-5-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1f][1,2,4]triazin-6-yl)phenyl)carbamate (22 mg, 0.04 mmol) in HCl / EtOAc. The reaction mixture was stirred at room temperature for 1 h and then concentrated to give 6-(4-aminophenyl)-5-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-4-amine (18 mg, 100%) as a white solid. MS(ESI): C 23 H 20 Calculated mass for N8O2: 440; observed m / z 441 [M+1] + .

[0214] Step 12: N-(4-(4-amino-5-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide A round bottom flask was charged with 6-(4-aminophenyl)-5-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-4-amine, DCM and a stir bar. The reaction mixture was cooled to 0° C., then TEA (1 drop) and acryloyl chloride (3.6 mg, 0.04 mmol) were added under N2. The reaction mixture was stirred at 0° C. for 10 min and then poured into ice water. The aqueous layer was extracted three times with DCM (5 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by pre-HPLC to give compound 1 (1.2 mg, 6%) as a white solid. MS(ESI):C 26 H 22 Calculated mass for N8O3: 494; Measured m / z 495 [M+H] + . 1H NMR(400MHz,MeOD) δ 8.40(d,J=5.1Hz,1H),8.08(s,1H),7.62(d,J=8.7Hz,2H),7.51(d,J=8.8Hz,2H),7.32(d,J=8.0Hz,1H),7.17(d,J=1.9Hz,1H),7.14 (d,J=5.1Hz,1H),7.09(dd,J=8.0,1.9Hz,1H),6.39(dd,J=13.7,5.9Hz,2H),5.77(dd,J=9.6,2.3Hz,1H),3.66(s,3H),2.52(s,3H).

[0215] Example 28 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide ("Compound 28") [ka] Step 1: N-(4-(4-amino-3-bromo-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide To a solution of 4-amino-3-bromo-2-iodo-1-methyl-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile (300 mg, 0.80 mmol), N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acrylamide (240 mg, 0.88 mmol) and KPO (504 mg, 2.4 mmol) in dioxane (10 ml) and HO (1.0 ml) was added Pd(PPh) (92 mg, 0.08 mmol) and the reaction was purged with nitrogen three times. The reaction mixture was irradiated in a microwave on a Biotage Smith Synthesizer at 80° C. for 1 h. The reaction mixture was concentrated under reduced pressure. The residue was washed with EtOAc (20 mL) and HO (20 mL) to give the desired product (226 mg) as a yellow solid. MS(ESI):C 18 H 14 Calculated mass for BrNO: 395; observed m / z 396 [M+1] + .

[0216] Step 2: 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide To a solution of N-(4-(4-amino-3-bromo-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide (100 mg, 0.25 mmol), 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(2,2,2-trifluoroethyl)benzamide (136 mg, 0.38 mmol), CsF (114 mg, 0.75 mmol) in DMF (1 ml) and HO (0.1 ml) was added Pd(DtBPF)Cl (33 mg, 0.05 mmol) and the reaction was purged with nitrogen three times. The mixture was stirred at 50 °C for 10 min. The mixture was quenched with water (10 mL) and extracted with EtOAc (10 mL x 3). The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (NH3) to give compound 28 (5.78 mg) as a white solid. MS (ESI): C 28 H 23 Calculated mass for F3N6O3: 548; measured m / z 549 [M+H] + . 1 H NMR(400MHz,DMSO) δ 10.28(s,1H),8.64(t,J=6.4Hz,1H),8.21(s,1H),7.72-7.64(m,3H),7.30(d,J=8.4Hz,2H),6.97(s,1H),6.89(d,J=8. 4Hz,1H),6.43(m,1H),6.30-6.24(m,1H),6.09(s,1H),5.81-5.75(m,1H),4.15-4.01(m,2H),3.81(s,3H),3.73(s,3H).

[0217] Example 71 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide ("Compound 71") [ka] Step 1: 4-Bromo-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide A mixture of 4-bromo-2-methoxybenzoic acid (800 mg, 3.5 mmol), 2,2,2-trifluoroethan-1-amine (412 mg, 4.2 mmol), T3P (6.6 g, 10.4 mmol) and DIPEA (1.8 g, 13.8 mmol) in THF (10 mL) was stirred at room temperature for 3 h. The reaction mixture was diluted with H2O (10 ml) and the solution was extracted with EtOAc (30 ml x 3), dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by FCC (PE / EA = 4 / 1) to give the product (800 mg, 74% yield) as a white solid. MS (ESI): C 10 Calculated mass for H9BrF3NO2: 311; Measured m / z 312 [M+H] + .

[0218] Step 2: 2-Methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(2,2,2-trifluoroethyl)benzamide A solution of 4-bromo-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide (800 mg, 2.6 mmol), B2Pin2 (0.98 g, 3.8 mmol), Pd(dppf)Cl2 (187 mg, 0.26 mmol) and KOAc (754 mg, 7.7 mmol) in dioxane (10 mL) was stirred at 80 °C under N2 for 16 h. The reaction mixture was concentrated under reduced pressure. The residue was purified by column chromatography (PE / EtOAc = 4 / 1) to give the product (900 mg, 98% yield) as a brown solid. MS (ESI): C 16 H 21 Calculated mass for BF3NO4: 359; measured m / z: 360 [M+H]+ .

[0219] Step 3: 2-Fluoro-N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acrylamide A solution of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (1.00 g, 4.6 mmol), 2-fluoroacrylic acid (493 mg, 5.5 mmol), T3P (8.7 g, 13.7 mmol) and DIPEA (2.36 g, 18.2 mmol) in THF (20 mL) was stirred at room temperature for 3 h. The residue was extracted with EtOAc, the organic layer was collected and then concentrated under reduced pressure. The crude was purified by FCC (PE / EA=10 / 1) to give the product (1.27 g, 96% yield) as a white solid. MS (ESI): 15 H 19 Calculated mass for BFNO3: 291; observed m / z 292 [M+H] + .

[0220] Step 4: 4-(4-amino-6-bromopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide A solution of 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(2,2,2-trifluoroethyl)benzamide (148 mg, 0.41 mmol), 6-bromo-5-iodopyrazolo[5,1-f][1,2,4]triazin-4-amine (200 mg, 0.59 mmol), Pd(PPh3)4 (68 mg, 0.04 mmol) and K2CO3 (245 mg, 1.77 mmol) in dioxane (2 mL) and HO (0.2 mL) was stirred at 100° C. for 2 h. The reaction mixture was diluted with HO (15 ml) and the solution was extracted with EtOAc (20 ml×3). The combined organic layers were washed with brine (10 ml), dried over Na2SO4, filtered and concentrated to give a residue. The residue was purified by FCC (PE / EtOAc=1 / 1) to give the product (100 mg, 55% yield) as a yellow oil. MS (ESI): 15 H 12Calculated mass for BrF3N6O2: 444; measured m / z: 445 [M+H] + .

[0221] Step 5: 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide A solution of 4-(4-amino-6-bromopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide (100 mg, 0.22 mmol), 2-fluoro-N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acrylamide (98 mg, 0.34 mmol), Pd(PPh3)4 (25 mg, 0.02 mmol) and K2CO3 (91 mg, 0.66 mmol) in dioxane (5 mL) and HO (0.5 mL) was stirred at 100° C. for 16 h. The reaction mixture was concentrated and the residue was purified by Prep-HPLC to give compound 71 (22.2 mg, 19% yield) as a white solid. MS(ESI):C 24 H 19 Calculated mass for F4N7O3: 529; measured m / z 530 [M+H] + . 1 H NMR(400MHz,DMSO) δ 10.36(s,1H),8.73(t,J=6.4Hz,1H),8.36(s,1H),8.17(s,1H),7.84(d,J=7.8Hz,1H),7.68(d,J=8.8Hz,2H),7.4 1(d,J=8.8Hz,2H),7.25(s,1H),7.04(dd,J=7.9,1.1Hz,1H),5.82-5.39(m,3H),4.21-4.07(m,2H),3.84(s,3H).

[0222] Example 96 4-(4-amino-7-cyano-2-(4-(2-fluoroacrylamide)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide ("Compound 96") [ka] Step 1: 2-Fluoro-N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acrylamide A mixture of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (1.00 g, 4.56 mmol), 2-fluoroacrylic acid (493 mg, 5.5 mmol), T3P (8.70 g, 13.7 mmol), DIPEA (2.36 g, 18.2 mmol) in THF (20 mL) was stirred at room temperature for 3 h. The reaction mixture was diluted with H2O (10 ml) and extracted with EtOAc. The organic layers were collected, then dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude was purified by FCC (PE / EA=10 / 1) to give the product (1.27 g, 96% yield) as a white solid. MS (ESI): C 15 H 19 Calculated mass for BFNO3: 291, measured m / z: 292 [M+H] + .

[0223] Step 2: N-(4-(4-amino-3-bromo-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)-2-fluoroacrylamide To a solution of 4-amino-3-bromo-2-iodo-1-methyl-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile (200 mg, 0.53 mmol) and 2-fluoro-N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acrylamide (154 mg, 0.53 mmol) in DMF / HO (5 mL / 1 mL) was added KCO (220 mg, 1.59 mmol), Pd(PPh) (58 mg, 0.05 mmol). The reaction mixture was stirred at 100 °C under N protection for 2 h. The mixture was concentrated under reduced pressure, and the residue was purified by gel-column chromatography (DCM:MeOH=10:1) to give N-(4-(4-amino-3-bromo-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)-2-fluoroacrylamide (200 mg, 91% yield) as a white solid. MS(ESI):C 18 H 13 Calculated mass for BrFNO: 413; observed m / z 414 [M+H] + .

[0224] Step 3: 4-(4-amino-7-cyano-2-(4-(2-fluoroacrylamide)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide To a solution of N-(4-(4-amino-3-bromo-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)-2-fluoroacrylamide (100 mg, 0.24 mmol) and 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(2,2,2-trifluoroethyl)benzamide (129 mg, 0.36 mmol) in DMF / HO (5 mL / 1 mL) was added CsF (109 mg, 0.72 mmol) and Pd(DtBPF)Cl (28 mg, 0.024 mmol). The reaction mixture was stirred at 50° C. for 2 h under N protection. The mixture was concentrated under reduced pressure and the residue was purified by Prep-HPLC to give compound 96 (31.42 mg) as a white solid. MS(ESI):C 28H 22 Calculated mass for F4N6O3: 566; measured m / z 567 [M+H] + . 1 H NMR(400MHz,DMSO) δ 10.41(s,1H),8.65(t,J=6.4Hz,1H),8.22(s,1H),7.76(d,J=8.8Hz,2H),7.69(d,J=7.6Hz,1H),7.33(d,J=8.4Hz,2H ),6.98(d,J=0.8Hz,1H),6.89(m,1H),6.10(s,2H),5.72(m,1H),5.45(m,1H),4.09(m,2H),3.81(s,3H),3.74(s,3H).

[0225] Example 100 4-(4-amino-6-(2-fluoro-4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide ("Compound 100") [ka] Step 1: 4-(4-amino-6-(4-amino-2-fluorophenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide A solution of 4-(4-amino-6-bromopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide (100 mg, 0.22 mmol), 3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (80 mg, 0.34 mmol), KCO (61 mg, 0.44 mmol) and Pd(PPh) (23 mg, 0.02 mmol) in dioxane (2.5 mL) and HO (0.7 mL) was stirred at 100° C. under N atmosphere for 16 h. The mixture was quenched with HO and extracted with EtOAc. The combined organic phase was washed with brine, dried over Na2SO4, concentrated under reduced pressure and purified by silica gel chromatography column (DCM / MeOH=95:5-10:1) to give the product (60 mg, 60% yield) as a yellow solid. LCMS (ESI) C 21 H 17 Calculated for F4N7O2: 476; m / z found: 476 [M+H] + .

[0226] Step 2: 4-(4-amino-6-(2-fluoro-4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide A solution of 4-(4-amino-6-(4-amino-2-fluorophenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide (60 mg, 0.13 mmol), 2-(trifluoromethyl)acrylic acid (27 mg, 0.20 mmol), DIPEA (32 mg, 0.26 mmol) and T3P (26 mg, 0.65 mmol) in THF (0.8 mL) was stirred at 0° C. for 5 h. The mixture was quenched with H2O and extracted with EtOAc. The combined organic phase was washed with brine, dried over Na2SO4, concentrated under reduced pressure, purified by silica gel chromatography column (DCM / MeOH=95:5-10:1) and further purified by Prep-HPLC to give compound 100 (8 mg, 20% yield) as a white solid. LCMS (ESI) C 24 H 18 Calculated for F5N7O3: 547; Found m / z 547 [M+H] + . 1 H NMR(400Hz,DMSO,ppm) 10.56(s,1H),8.67(m,1H),8.21(s,1H),7.76(d,J=7.9Hz,1H),7.70-7.57(m,2H),7.44(t,J=8 .4Hz,1H),7.11(s,1H),6.92(m,1H),5.74(m,1H),5.48(m,1H),4.17-4.05(m,2H),3.79(s,3H).

[0227] Example 338 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(3,3-difluorocyclobutyl)benzamide ("Compound 338") [ka] Step 1: N-(3,3-difluorocyclobutyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide To a solution of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid (500 mg, 2.0 mmol) and 3,3-difluorocyclobutan-1-amine (281 mg, 2.6 mmol) and DIPEA (780 mg, 6.0 mmol) in THF (10 mL) was added T3P (1.93 g, 3.0 mmol). The reaction mixture was stirred at room temperature for 3 h. The reaction mixture was extracted with EA and HO, and the organic layer was collected. The reaction mixture was purified by silica gel chromatography (eluted with PE / EA=5 / 1) to give the desired product (585 mg, 86% yield) as a white solid. MS (ESI): C 17 H 22 Calculated mass for BF2NO3: 337; measured m / z 338 [M+1] + .

[0228] Step 2: 4-(4-amino-6-bromopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(3,3-difluorocyclobutyl)benzamide To a solution of N-(3,3-difluorocyclobutyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (250 mg, 0.74 mmol), 6-bromo-5-iodopyrazolo[5,1-f][1,2,4]triazin-4-amine (200 mg, 0.59 mmol), K2CO3 (205 mg, 1.48 mmol) in dioxane (8 ml) and H2O (1 ml) was added Pd(PPh3)4 (86 mg, 0.07 mmol) and the reaction was purged with nitrogen three times. The mixture was stirred at 100° C. for 16 h. The residue was purified by silica gel chromatography (eluted with DCM / MeOH=20 / 1) to give the desired product (146 mg, 47% yield) as a yellow solid. MS(ESI):C 16 H 13 Calculated mass for BrF2N6O: 422, measured m / z: 423 [M+1] + .

[0229] Step 3: 4-(4-amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(3,3-difluorocyclobutyl)benzamide To a solution of 4-(4-amino-6-bromopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(3,3-difluorocyclobutyl)benzamide (90 mg, 0.21 mmol), 6-bromo-5-iodopyrazolo[5,1-f][1,2,4]triazin-4-amine (93 mg, 0.32 mmol) and K2CO3 (59 mg, 0.43 mmol) in dioxane (5 ml) and H2O (1 ml) was added Pd(PPh3)4 (25 mg, 0.02 mmol) and the reaction was purged with nitrogen three times. The mixture was stirred at 100° C. for 16 h. The residue was purified by silica gel chromatography (eluted with DCM / MeOH=20 / 1) to give the crude product. The crude product was then purified by semi-preparative HPLC to give compound 338 (26.51 mg, 25% yield) as a white solid. MS (ESI): 25 H 20 Calculated mass for F3N7O2: 507; measured m / z: 508 [M+1] + . 1 H NMR(400MHz,DMSO) δ 10.37(s,1H),8.98(s,1H),8.17(s,1H),7.98(d,J=8.0Hz,2H),7.67(d,J=8.0Hz,2H),7.53(d,J=8.0Hz,2H),7.36 (d,J=8.0Hz,2H),5.78-5.65(m,1H),5.46-5.41(m,1H),4.35-4.25(m,1H),3.01-2.92(m,2H),2.86-2.72(m,2H).

[0230] Example 339 N-(4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxyphenyl)-2,2-difluorocyclopropane-1-carboxamide ("Compound 339") [ka] Step 1: N-(4-(4-amino-6-bromopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxyphenyl)-2,2-difluorocyclopropane-1-carboxamide To a solution of 2,2-difluoro-N-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclopropane-1-carboxamide (187 mg, 0.53 mmol), 6-bromo-5-iodopyrazolo[5,1-f][1,2,4]triazin-4-amine (150 mg, 0.44 mmol) and K2CO3 (116 mg, 0.84 mmol) in dioxane (10 ml) and H2O (3 ml) was added Pd(PPh3)4 (48 mg, 0.04 mmol) and the reaction was purged with nitrogen three times. The reaction mixture was stirred at 100° C. for 16 hours. The reaction mixture was purified by silica gel chromatography (eluted with DCM / MeOH=10 / 1) to give the desired product (100 mg, 54% yield) as a yellow solid. MS (ESI): C 16 H 13 Calculated mass for BrF2N6O2: 439; observed m / z 440 [M+1] + .

[0231] Step 2: N-(4-(6-(4-acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxyphenyl)-2,2-difluorocyclopropane-1-carboxamide To a solution of N-(4-(4-amino-6-bromopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxyphenyl)-2,2-difluorocyclopropane-1-carboxamide (100 mg, 0.23 mmol), N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acrylamide (124 mg, 0.46 mmol), K2CO3 (63 mg, 0.46 mmol) in dioxane (5 ml) and HO (2 ml) was added Pd(PPh3)4 (23 mg, 0.02 mmol) and the reaction was purged with nitrogen three times. The mixture was stirred at 100 °C for 16 h. The residue was purified by prep-HPLC to give the desired compound 339 (24.65 mg, 21% yield) as a white solid. MS(ESI):C 25 H 21 Calculated mass for F2N7O3: 505; measured m / z 506 [M+1] + . 1 H NMR(400MHz,DMSO) δ 10.21(s,1H),9.86(s,1H),8.15(d,J=7.8Hz,2H),7.62(d,J=8.7Hz,2H),7.43(d,J=8.7Hz,2H),7.12(d,J=1.4Hz,1H),6.96(d,J=8.1Hz,1H ),6.43(dd,J=17.0,10.0Hz,1H),6.25(dd,J=17.0,1.9Hz,1H),5.76(dd,J=10.0,2.0Hz,1H),3.80(s,3H),3.24(m,1H),2.06-1.93(m,2H).

[0232] Example 343 N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)methacrylamide ("Compound 343") [ka] A mixture of N-(4-(4-amino-3-bromo-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)methacrylamide (70 mg, 0.17 mmol), 2-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)-4-methylpyrimidine (113 mg, 0.34 mmol), Pd(DtBPF)Cl (7 mg, 0.01 mmol) and CsF (52 mg, 0.34 mmol) in DMF / H2O (3 mL / 0.3 mL) was stirred at 50 °C under N2 for 2 h. The reaction mixture was concentrated under reduced pressure. The residue was purified by prep-HPLC to give the desired compound 343 (14.5 mg, 17% yield) as a white solid. MS (ESI): C 30 H 24 Calculated mass for FN7O2: 533.57, measured m / z: 534 [M+1] + . 1 H NMR(400MHz,DMSO) δ 9.94(s,1H),8.47(d,J=5.0Hz,1H),8.21(s,1H),7.75(d,J=8.5Hz,2H),7.36(s,1H),7.31(d,J=8.5Hz,2H),7.24(dd,J=11.3 ,1.8Hz,1H),7.18(d,J=5.0Hz,1H),7.12(d,J=8.2Hz,1H),5.79(s,1H),5.54(s,1H),3.80(s,3H),2.41(s,3H),1.95(s,3H).

[0233] Example 344 N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)-2-fluoroacrylamide ("Compound 344") [ka] A mixture of N-(4-(4-amino-3-bromo-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)-2-fluoroacrylamide (70 mg, 0.17 mmol), 2-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)-4-methylpyrimidine (112 mg, 0.34 mmol), Pd(DtBPF)Cl2 (7 mg, 0.01 mmol) and CsF (52 mg, 0.34 mmol) in DMF / HO (3 mL / 0.3 mL) was stirred at 50 °C under N2 for 2 h. The reaction was concentrated under reduced pressure. The residue was purified by prep-HPLC to give the desired compound 344 (15 mg, 16% yield) as a white solid. MS (ESI): C 29 H 21 Calculated mass for F2N7O2: 537; observed m / z 538 [M+1] + . 1 H NMR(400MHz,DMSO) δ 10.44(s,1H),8.47(d,J=5.0Hz,1H),8.21(s,1H),7.80(d,J=8.7Hz,2H),7.35(d,J=8.6Hz,3H),7.25(dd,J=11.3,2.0Hz,1H),7.19(d,J= 5.0Hz,1H),7.14-7.11(m,1H),5.79(d,J=3.7Hz,0.5H),5.67(d,J=3.7Hz,0.5H),5.46(dd,J=15.6,3.7Hz,1H),3.80(s,3H),2.41(s,3H).

[0234] Example 346 N-(4-(4-amino-5-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)methacrylamide ("Compound 346") [ka] Step 1: 6-Bromo-5-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-4-amine To a solution of 2-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)-4-methylpyrimidine (293 mg, 0.89 mmol), 6-bromo-5-iodopyrazolo[5,1-f][1,2,4]triazin-4-amine (200 mg, 0.59 mmol) and K2CO3 (163 mg, 1.2 mmol) in dioxane (8 ml) and H2O (2 ml) was added Pd(PPh3)4 (68 mg, 0.06 mmol) and the reaction was purged with nitrogen three times. The mixture was stirred at 100° C. for 16 hours. The residue was purified by silica gel chromatography (eluted with DCM / MeOH=10 / 1) to give the desired product (200 mg, 82% yield) as a yellow solid. MS(ESI):C 16 H 11 Calculated mass for BrFNO: 415; observed m / z 416 [M+1] + .

[0235] Step 2: N-(4-(4-amino-5-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)methacrylamide To a solution of 6-bromo-5-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-4-amine (200 mg, 0.482 mmol), N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methacrylamide (208 mg, 0.723 mmol) and K2CO3 (134 mg, 0.048 mmol) in dioxane (8 ml) and H2O (2 ml), Pd(PPh3)4 (56 mg, 0.05 mmol) was added and the reaction was purged with nitrogen three times. The mixture was stirred at 100° C. for 16 h. The residue was purified by silica gel chromatography (eluted with DCM / MeOH=10 / 1) to give the crude product. The crude product was then purified by Prep-HPLC to give compound 346 (10.75 mg, 4.5% yield) as a white solid. MS(ESI):C 26 H 21Calculated mass for FN8O2: 496; observed m / z 497 [M+1] + . 1 H NMR(400MHz,DMSO) δ 9.88(s,1H),8.53(d,J=4.0Hz,1H),8.16(s,1H),7.67(d,J=12.0Hz,2H),7.48(m,2H),7.39(d,J=12.0Hz ,2H),7.28(d,J=8.0Hz,1H),7.23(d,J=4.0Hz,1H),5.79(s,1H),5.52(s,1H),2.45(s,3H),1.94(s,3H).

[0236] Example 355 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-(methyl-d3)-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide [ka] Step 1: 3-Bromo-4-chloro-1-(methyl-d3)-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile A mixture of 3-bromo-4-chloro-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile (1 g, 3.8 mmol) and NaH (273 mg, 11.4 mmol) in DMF (7 mL) was stirred at 0 °C under N for 0.5 h, then CD3I (1.1 g, 7.6 mmol) was added. The reaction mixture was stirred at room temperature under N2 for 2 h. The reaction mixture was extracted with water (15 mL) and EtOAc (10 mL x 3). The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by FCC (PE / EtOAc = 1:1) to give the desired target (800 mg, 80% yield) as a yellow solid. MS (ESI): mass calculated for CH2D3BrClN3: 273; m / z found 274 [M+1] + .

[0237] Step 2: 4-Amino-3-bromo-1-(methyl-d3)-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile A mixture of 3-bromo-4-chloro-1-(methyl-d3)-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile (800 mg, 2.9 mmol), NH3·H2O (5 mL) in 1,4-dioxane (5 mL) was stirred at 100 °C for 16 h in a sealed tube. The reaction was concentrated under reduced pressure to give the desired target (600 mg, 80% yield) as a yellow solid. MS (ESI): mass calculated for C9H4D3BrN4: 254; m / z found 255 [M+1] + .

[0238] Step 3: 4-Amino-3-bromo-2-iodo-1-(methyl-d3)-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile A mixture of 4-amino-3-bromo-1-(methyl-d3)-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile (650 mg, 2.56 mmol), NIS (632 mg, 2.81 mmol) and TFA (3 drops) in DMF (7 mL) was stirred at 25° C. for 16 h. The reaction mixture was extracted with water (15 mL) and EtOAc (10 mL×3). The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure to give the desired target (600 mg, 62% yield) as a yellow solid. MS (ESI): mass calculated for C9H3D3BrIN4: 380; m / z found 381 [M+1] + .

[0239] Step 4: N-(4-(4-amino-3-bromo-7-cyano-1-(methyl-d3)-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide A mixture of 4-amino-3-bromo-2-iodo-1-(methyl-d3)-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile (600 mg, 1.57 mmol), N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acrylamide (431 mg, 1.57 mmol), Pd(PPh3)4 (181 mg, 0.15 mmol) and K3PO4 (450 mg, 3.14 mmol) in DMF / H2O (6 mL / 2 mL) was stirred at 80 °C under N2 in a microwave for 1 h. The reaction mixture was diluted with water (10 mL) and extracted with EtOAc (5 mL x 3). The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by prep-TLC (EtOAc in PE=70%) to give the desired product (400 mg, 64% yield) as a yellow solid. MS (ESI): 18 H 11 Calculated mass for D3BrNO: 399; observed m / z 400 [M+1] + .

[0240] Step 5: 4-(2-(4-acrylamidophenyl)-4-amino-7-cyano-1-(methyl-d3)-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide A mixture of N-(4-(4-amino-3-bromo-7-cyano-1-(methyl-d3)-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide (80 mg, 0.2 mmol), 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(2,2,2-trifluoroethyl)benzamide (144 mg, 0.4 mmol), Pd(DtBPF)Cl2 (13 mg, 0.02 mmol) and CsF (61 mg, 0.4 mmol) in DMF / H2O (3 mL / 0.3 mL) was stirred at 50 °C under N2 for 2 h. The reaction mixture was diluted with water (10 mL) and extracted with EtOAc (5 mL x 3). The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by Prep-HPLC to give the desired compound 355 (29.64 mg, 27% yield) as a white solid. MS(ESI):C28 H 20 Calculated mass for D3F3N6O3: 551; observed m / z 552 [M+1] + . 1 H NMR(400MHz,DMSO) δ 10.28(s,1H),8.65(s,1H),8.21(s,1H),7.71-7.67(m,3H),7.30(d,J=8.6Hz,2H),6.98-6.88(m,2H),6.41(d,J=1 0.1Hz,1H),6.27(dd,J=17.0,1.9Hz,1H),5.78(dd,J=10.0,2.0Hz,1H),4.08(dd,J=9.6,6.5Hz,2H),3.73(s,3H).

[0241] Example 398 N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide ("Compound 398") [ka] Step 1: N-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methacrylamide A mixture of 3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (3.0 g), methacryloyl chloride (1.45 g) and TEA (1.92 g) in DCM (20 mL) was stirred at 0° C. for 2 h and at 20° C. for 1 h. The reaction mixture was concentrated under reduced pressure. The residue was purified by FCC (60 g silica gel, 20% EtOAc in PE) to give the desired target (3.1 g) as a white solid. MS (ESI): C 16 H 21 Calculated mass for BFNO3: 305, measured m / z: 306 [M+1] + .

[0242] Step 2: N-(4-(4-amino-3-bromo-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide A mixture of N-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methacrylamide (3.5 g), 4-amino-3-bromo-2-iodo-1-methyl-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile (3.1 g), Pd(PPh3)4 (861 mg) and K3PO4 (6.0 g) in DMF / H2O (50 mL / 5 mL) was stirred at 70 °C for 10 h under N2. The reaction mixture was quenched with water (130 mL). The precipitate was filtered to give the desired target (2.5 g) as a light brown solid. MS (ESI): C 19 H 15 Calculated mass for BrFNO: 427, measured m / z: 428 [M+1] + .

[0243] Step 3: N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide A mixture of N-(4-(4-amino-3-bromo-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide (1.0 g), 2-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)-4-methylpyrimidine (1.16 g), Pd(DtBPF)Cl2 (55 mg) and CsF (1.06 g) in DMF / H2O (10 mL / 1 mL) was stirred at 50° C. under N2 for 6 h. The reaction mixture was quenched with water (50 mL). The residue was filtered to give the crude mixture as a light brown solid. The residue was purified by FCC (60 g silica gel, MeOH=10% in DCM) followed by Prep-HPLC to give the desired compound 398 (508.63 mg) as a white solid. MS(ESI):C 30 H 23Calculated mass for F2N7O2: 551, measured m / z: 552 [M+1] + . 1 H NMR(400MHz,DMSO) δ 10.15(s,1H),8.47(d,J=5.0Hz,1H),8.23(s,1H),7.79(dd,J=12.4,1.8Hz,1H),7.54(dd,J=8.4,1.9Hz,1H),7.35(dd,J=8.4,4.7Hz,2H) ,7.23(d,J=11.5Hz,1H),7.18(d,J=5.1Hz,1H),7.10(d,J=8.0Hz,1H),5.82(s,1H),5.58(s,1H),3.75(s,3H),2.40(s,3H),1.95(s,3H).

[0244] Example 459 N-(4-(4-amino-7-cyano-3-(4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide ("Compound 459") [ka] Step 1: 2-(4-bromophenoxy)-5-fluoro-4-methylpyrimidine To a solution of 2-chloro-5-fluoro-4-methylpyrimidine (300 mg, 2.1 mmol) and 4-bromophenol (355 mg, 3.1 mmol) in DMF (3 mL) was added Cs2CO3 (1.0 g, 3.075 mmol). The reaction mixture was stirred at 100 °C for 4 h and then concentrated under reduced pressure. The residue was purified by gel-column chromatography (PE:EA = 20:1) to give 2-(4-bromophenoxy)-5-fluoro-4-methylpyrimidine (400 mg, 69% yield) as a white oil. MS (ESI): mass calculated for C11H8BrFN2O: 282; m / z found 283 [M+H] + .

[0245] Step 2: 5-Fluoro-4-methyl-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)pyrimidine To a solution of 2-(4-bromophenoxy)-5-fluoro-4-methylpyrimidine (420 mg, 1.5 mmol), B2Pin2 (568 mg, 2.2 mmol) and AcOK (294 mg, 3.0 mmol) in dioxane / HO (20 mL) was added Pd(dppf)Cl2 (54 mg, 0.075 mmol). The reaction mixture was stirred at 80 °C for 16 h. The residue was purified by gel-column chromatography (PE:EA = 20:1) to give 5-fluoro-4-methyl-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)pyrimidine (200 mg, 43% yield) as a white solid. MS (ESI): C 17 H 20 Calculated mass for BFN2O3: 330; observed m / z 331 [M+H] + .

[0246] Step 3: N-(4-(4-amino-7-cyano-3-(4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide To a solution of N-(4-(4-amino-3-bromo-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide (70 mg, 0.16 mmol), 5-fluoro-4-methyl-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)pyrimidine (89 mg, 0.27 mmol) and CsF (50 mg, 0.33 mmol) in DMF / HO (2.0 / 0.2 mL) was added Pd(DtBPF)Cl (11 mg, 0.016 mmol). The reaction mixture was stirred at 50° C. for 2 h. The mixture was concentrated and the residue was purified by gel-column chromatography (DCM:MeOH=20:1) to give compound 459 (10.80 mg, 8% yield) as a white solid. MS(ESI):C 30 H23 Calculated mass for F2N7O2: 551, measured m / z: 552 [M+H] + . 1 H NMR(400MHz,DMSO) δ 10.13(s,1H),8.55(d,J=1.2Hz,1H),8.21(s,1H),7.77(m,1H),7.51(m,1H),7.30(t,J=8.4Hz,3H) ,7.20(d,J=8.8Hz,2H),5.81(s,1H),5.58(s,1H),3.75(s,3H),2.40(d,J=2.8Hz,3H),1.94(s,3H).

[0247] Example 474 N-(4-(4-amino-7-cyano-1-methyl-3-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide ("Compound 474") [ka] Step 1: N-(3-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methacrylamide To a solution of 3-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (1 g, 4 mmol) and TEA (0.81 g, 8 mmol) in DCM (10 mL) was added methacryloyl chloride (0.40 g, 4 mmol) at 0° C. The reaction mixture was stirred at room temperature for 1 h. The reaction mixture was concentrated to give the crude product. The crude product was purified by flash chromatography to give 1.1 g of N-(3-chloro-4-(4,4,5,5-tetramethyl-(1,3,2-dioxaborolan-2-yl)phenyl)methacrylamide as a yellow oil. MS (ESI): C 16 H 21 Calculated mass for BClNO3: 321, observed m / z 322 [M+H] + .

[0248] Step 2: N-(4-(4-amino-3-bromo-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide A solution of N-(3-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methacrylamide (1.1 g, 3 mmol), 4-amino-3-bromo-2-iodo-1-methyl-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile (1.13 g, 3 mmol), KPO (1.27 g, 6 mmol) in DMF (20 mL) and HO (4 mL) was stirred at 80° C. for 12 h. The reaction mixture was poured into water, filtered, and the filter cake was collected to give 800 mg of N-(4-(4-amino-3-bromo-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide as a pale yellow solid. MS (ESI): C 19 H 15 Calculated mass for BrClNO: 443, observed m / z 444 [M+H] + .

[0249] Step 3: N-(4-(4-amino-7-cyano-1-methyl-3-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide A mixture of N-(4-(4-amino-3-bromo-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide (100 mg, 0.22 mmol), 4-methyl-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)pyrimidine (69 mg, 0.22 mmol), CsF (67 mg, 0.44 mmol) and Pd(DtBPF)Cl2 (14 mg, 0.022 mmol) in DMF (5 mL) and HO (1 mL) was stirred at 50° C. for 2 h. The reaction mixture was poured into water and filtered. The filter cake was collected to give the crude product. The crude product was purified by prep-HPLC to give compound 474 (15.56 mg) as a white solid. MS(ESI):C 30 H24 Calculated mass for ClNO2: 549; observed m / z 550 [M+H] + . 1 H NMR(400MHz,DMSO) δ 10.08(s,1H),8.45(d,J=5.0Hz,1H),8.21(s,1H),8.03(d,J=2.0Hz,1H),7.68(dd,J=8.4,2.0Hz,1H),7.38(d,J=8.4Hz,1H),7.29 (d,J=7.4Hz,2H),7.19(d,J=8.8Hz,2H),7.14(d,J=5.0Hz,1H),5.82(s,1H),5.57(s,1H),3.69(s,3H),2.39(s,3H),1.94(s,3H).

[0250] Example 488 N-(4-(4-amino-7-cyano-1-methyl-3-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide ("Compound 488") [ka] Step 1: N-(3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methacrylamide To a solution of 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (1.6 g, 6.9 mmol) and TEA (1.0 g, 10.3 mmol) in DCM (20 mL) under N2, methacryloyl chloride (789.0 mg, 7.5 mmol) was added dropwise at 0° C. The mixture was warmed to 25° C. and stirred for 3 h. Water (200 ml) was then added to the mixture and extracted with DCM (10 ml×3). The organic layer was dried over Na2SO4, concentrated, and the residue was purified by flash chromatography column (DCM:PE=0:100-100:0) to give N-(3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methacrylamide (1.7 g, 93% yield) as a yellow solid. MS(ESI):C 17 H24 Calculated mass for BNO3: 301; Measured m / z 302 [M+H] + .

[0251] Step 2: N-(4-(4-amino-3-bromo-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide To a solution of 4-amino-3-bromo-2-iodo-1-methyl-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile (500.0 mg, 1.3 mmol) and N-(3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methacrylamide (479.5 mg, 1.6 mmol) in DMF / H2O (5 mL / 0.5 mL) was added Pd(PPh3)4 (153.7 mg, 0.13 mmol) and K3PO4 (844.5 mg, 4.0 mmol). Under N2 protection, the reaction mixture was stirred at 80 °C under microwave for 70 min. The mixture was quenched with water (50 ml) and extracted with EA (20 ml x 3). The organic layer was dried over Na2SO4 and concentrated. The residue was purified by flash chromatography column (MeOH:DCM=0:100 to 5:95) to give N-(4-(4-amino-3-bromo-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide (250 mg, 45% yield) as a yellow solid. MS(ESI):C 20 H 18 Calculated mass for BrNO: 423; Found m / z 424 [M+H] + .

[0252] Step 3: N-(4-(4-amino-7-cyano-1-methyl-3-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide To a solution of N-(4-(4-amino-3-bromo-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide (250.0 mg, 0.59 mmol) and 4-methyl-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)pyrimidine (183.9 mg, 0.59 mmol) in DMF / H2O (2 mL / 0.2 mL) was added Pd(dtbpf)Cl2 (38.1 mg, 0.059 mmol) and CsF (178.9 mg, 1.18 mmol). The reaction mixture was stirred at 50 °C under N2 protection for 2 h. 20 ml of water was added to the mixture and extracted with EA (10 ml × 3). The organic layer was dried over Na2SO4 and concentrated. The residue was purified by pre-HPLC to give compound 488 (22.5 mg) as a white solid. MS(ESI):C 31 H 27 Calculated mass for N7O2: 529; measured m / z 530 [M+H] + . 1 H NMR(400MHz,DMSO) δ 9.86(s,1H),8.45(d,J=5.2Hz,1H),8.37(s,1H),7.65(d,J=1.6Hz,1H),7.60(dd,J=8.4,2.0Hz,1H),7.30-7.23(m,3H),7. 18(d,J=8.8Hz,3H),7.15(d,J=5.2Hz,1H),5.79(s,1H),5.53(s,1H),3.69(s,3H),2.39(s,3H),1.98(s,3H),1.94(s,3H).

[0253] Example 499 N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide ("Compound 499") [ka] To a solution of N-(4-(4-amino-3-bromo-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide (80 mg, 0.19 mmol), 3-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)-1-methyl-1H-pyrazole (89 mg, 0.29 mmol) and CsF (90 mg, 0.57 mmol) in dioxane (8 ml) and H2O (2 ml) was added Pd(DtBPF)Cl2 (24 mg, 0.02 mmol). The reaction mixture was stirred at 50 °C for 1 h. The residue was purified by silica gel chromatography (eluted with DCM / MeOH=10 / 1) to give the crude product, which was then purified by Prep-HPLC to give compound 499 (27.91 mg, 34.2% yield) as a white solid. MS(ESI):C 25 H 20 Calculated mass for FN9O: 539; observed m / z 540 [M+1] + . 1 H NMR(400MHz,DMSO) δ 10.13(s,1H),8.21(s,1H),7.76(dd,J=12.4,1.8Hz,1H),7.63(d,J=2.4Hz,1H),7.51(dd,J=8.4,2.0Hz,1H),7.29(t,J=8.4H) z,1H),7.16(t,J=8.6Hz,2H),6.99(d,J=8.0Hz,1H),5.88-5.80(m,2H),5.58(s,1H),3.74(s,3H),3.72(s,3H),1.95(s,3H).

[0254] Example 501 N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide ("Compound 501") [ka] To a solution of N-(4-(4-amino-3-bromo-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide (190.0 mg, 0.45 mmol) and 2-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)-4-methylpyrimidine (147.9 mg, 0.45 mmol) in DMF / HO (2 mL / 0.2 mL) was added Pd(dtbpf)Cl (29.1 mg, 0.045 mmol) and CsF (136.1 mg, 0.90 mmol). The reaction mixture was stirred at 50° C. for 2 h under N protection. 20 ml of water was added to the mixture and extracted with EA (10 ml×3). The organic layer was dried over Na2SO4 and concentrated. The residue was purified by pre-HPLC to give compound 501 (26.0 mg) as a white solid. MS(ESI):C 31 H 26 Calculated mass for FN7O2: 547; observed m / z 548 [M+H] + . 1 H NMR(400MHz,DMSO) δ 9.89(s,1H),8.46(d,J=5.2Hz,1H),8.39(s,1H),7.67(s,1H),7.65-7.58(m,1H),7.35(t,J=8.4Hz,1H),7.27(d,J=8.4Hz,1H),7.21(dd,J=11 .6,2.0Hz,1H),7.18(d,J=5.2Hz,1H),7.07(d,J=10.0Hz,1H),5.80(s,1H),5.53(s,1H),3.70(s,3H),2.40(s,4H),1.98(s,3H),1.94(s,3H).

[0255] Example 513 N-(4-(4-amino-7-cyano-1-methyl-3-(4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide ("Compound 513") [ka] A mixture of N-(4-(4-amino-3-bromo-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide (100 mg, 0.22 mmol), 1-methyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)-1H-pyrazole (98 mg, 0.22 mol), CsF (71 mg, 0.44 mmol) and Pd(DtBPF)Cl2 (14 g, 0.022 mmol) in DMF (10 mL) and HO (1 mL) was stirred at 50 °C under N2 for 2 h. The reaction mixture was concentrated under reduced pressure. The residue was purified by prep-HPLC to give compound 513 (12.31 mg) as a white solid. MS (ESI): C 29 H 24 Calculated mass for ClN7O2: 537, observed m / z 538 [M+H] + . 1 H NMR(400MHz,DMSO) δ 10.08(s,1H),8.20(s,1H),8.01(d,J=2.0Hz,1H),7.64(d,J=2.3Hz,2H),7.33(d,J=8.4Hz,1H),7.20(d,J=6.9Hz,2 H),7.02(d,J=8.8Hz,2H),5.88(d,J=2.3Hz,1H),5.82(s,1H),5.58(s,1H),3.74(s,3H),3.68(s,3H),1.94(s,3H).

[0256] Example 507 N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide ("Compound 507") [ka] Step 1: 2,5-Dichloro-4-methylpyrimidine To a solution of 2,4,5-trichloropyrimidine (3.0 g, 16.5 mmol) and Fe(acac)3 (1.16 g, 3.3 mmol) in NMP (3 mL) and THF (18 mL) was added methylmagnesium iodide (5.5 g, 33.0 mmol). The mixture was stirred at 25° C. for 12 h. The residue was extracted with EA and H2O. The organic layer was collected and concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluted with PE / EA=20 / 1) to give the desired product (1.1 g, 41% yield) as a pale yellow oil. MS (ESI): mass calculated for C5H4Cl2N2: 162; m / z found 163 [M+1] + .

[0257] Step 2: 2-(4-bromo-2-fluorophenoxy)-5-chloro-4-methylpyrimidine To a solution of 2,5-dichloro-4-methylpyrimidine (1.1 g, 6.9 mmol) and Cs2CO3 (4.43 g, 13.6 mmol) in DMF (25 ml) was added 4-bromo-2-fluorophenol (1.42 g, 7.5 mmol). The mixture was stirred at 100° C. for 12 h. The residue was purified by silica gel chromatography (eluted with PE / EA=20 / 1) to give the desired product (1.3 g, 61% yield) as a yellow oil. MS (ESI): C 11 Calculated mass for H7BrClFN2O: 316; measured m / z: 317 [M+1] + .

[0258] Step 3: 5-chloro-2-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)-4-methylpyrimidine To a solution of 2-(4-bromo-2-fluorophenoxy)-5-chloro-4-methylpyrimidine (1.3 g, 4.1 mmol), B2Pin2 (1.57 g, 6.2 mmol) and KOAc (806 mg, 8.2 mmol) in dioxane (25 ml), Pd(dppf)Cl2 (343 mg, 0.42 mmol) was added and purged with nitrogen three times. The mixture was stirred at 80° C. for 16 h. The residue was purified by silica gel chromatography (eluted with PE / EA=20 / 1) to give the desired product (1.25 g, 84% yield) as a pale green solid. MS (ESI): C 17 H 19 Calculated mass for BClFN2O3: 364; observed m / z 365 [M+1] + .

[0259] Step 4: N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide To a solution of 5-chloro-2-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)-4-methylpyrimidine (150 mg, 0.40 mmol), N-(4-(4-amino-3-bromo-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide (80 mg, 0.20 mmol) and CsF (61 mg, 0.40 mmol) in DMF (5 ml) and HO (0.5 ml) was added Pd(DtBPF)Cl (13 mg, 0.02 mmol). The reaction mixture was stirred at 50° C. for 2 h. The residue was purified by silica gel chromatography (eluted with DCM / MeOH=10 / 1) to give the crude product, which was then purified by Prep-HPLC to give compound 507 (23.36 mg, 21% yield) as a white solid. MS(ESI):C 29 H 21 Calculated mass for ClFN7O2: 553; observed m / z 554 [M+1] + . 1H NMR(400MHz,DMSO) δ 10.34(s,1H),8.63(s,1H),8.42(s,1H),7.76-7.74(d,J=8.0Hz,2H),7.42-7.38(t,J=8.0Hz,1H),7.33-7.31(d,J=8.0Hz,2H ),7.30-7.27(m,1H),7.13-7.11(m,1H),6.48-6.41(m,1H),6.30-6.26(m,1H),5.81-5.78(m,1H),3.85(s,3H),2.47(s,3H).

[0260] Example 532 4-(3-acrylamido-12-amino-9-cyano-6,7-dihydrobenzo[f]pyrido[3',4':4,5]pyrrolo[1,2-d][1,4]oxazepin-13-yl)-N-(3,3-difluorocyclobutyl)-2-methoxybenzamide ("Compound 532") [ka] Step 1: (2-(2-bromo-5-nitrophenoxy)ethoxy)(tert-butyl)dimethylsilane To a solution of 2-bromo-5-nitrophenol (2 g, 9.17 mmol, 1.0 equiv.), 2-((tert-butyldimethylsilyl)oxy)ethan-1-ol (1.94 g, 11 mmol, 1.2 equiv.), PPh3 (3.6 g, 13.8 mmol, 1.5 equiv.) in THF (40 mL) was added DIAD (2.78 g, 13.8 mmol, 1.5 equiv.) at 0° C. under N2 atmosphere. The mixture was stirred at room temperature for 16 h. The reaction mixture was concentrated and purified by silica gel chromatography column (PE:EtOAc=5:1) (3 g, 80% yield) as a yellow oil. LCMS (ESI) C 14 H 22 Calculated for BrNO4Si: 375; Found: 376 [M+1] + .

[0261] Step 2: 4-Bromo-3-(2-((tert-butyldimethylsilyl)oxy)ethoxy)aniline To a solution of (2-(2-bromo-5-nitrophenoxy)ethoxy)(tert-butyl)dimethylsilane (3.0 g, 7.98 mmol, 1.0 equiv) in AcOH (40 mL) was added Fe (4.5 g, 79.8 mmol, 10 equiv). The reaction mixture was stirred at room temperature for 2 h. The mixture was concentrated and purified by silica gel chromatography column (PE:EtOAc=3:1) as a yellow oil (2 g, crude). LCMS (ESI) C 14 H 24 Calculated for BrNO2Si: 345; Found: 346 [M+1] + .

[0262] Step 3: 3-(2-((tert-butyldimethylsilyl)oxy)ethoxy)-4-(4,4,5,5-tetramethyl-1,3,2 dioxaborolan-2-yl)aniline To a solution of 4-bromo-3-(2-((tert-butyldimethylsilyl)oxy)ethoxy)aniline (1.80 g, 5.2 mmol, 1.0 equiv), B2Pin2 (1.98 g, 7.8 mmol, 1.5 equiv), KOAc (1.02 g, 0.54 mmol, 2.0 equiv) in DMSO (15 mL) was added Pd(OAc)2 (238 mg, 1.04 mmol, 0.2 equiv) and PCy3 (582 mg, 2.08 mmol, 0.4 equiv). The reaction mixture was stirred at 50 °C under N2 protection for 16 h. The mixture was quenched with H2O and extracted with EtOAc. The combined organic phase was washed with brine, dried over Na2SO4, concentrated under reduced pressure and purified by FCC (DCM:MeOH = 20:1) to give the product (800 mg) as a black solid. LCMS(ESI) C 20 H 36 Calculated for BNO4Si: 393; Found: 394 [M+1] + .

[0263] Step 4: 4-(4-amino-6-(4-(2-fluoroacrylamide)-2-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclopropyl-2-methoxybenzamide To a solution of 3-(2-((tert-butyldimethylsilyl)oxy)ethoxy)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (1.3 g, 3.3 mmol, 1.35 equiv), 4-amino-3-bromo-2-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile (1.22 g, 2.47 mmol, 1.0 equiv) in DMF / HO (15 / 1.5 mL) was added KCO (680 mg, 4.94 mmol, 2 equiv) and Pd(PPh) (285 mg, 0.25 mmol, 0.05 equiv) and the reaction mixture was stirred at 100 °C under N atmosphere for 16 h. The mixture was quenched with H2O and extracted with EtOAc. The combined organic phase was washed with brine, dried over Na2SO4, concentrated under reduced pressure and purified by FCC to give the product (1 g, 80% purity). LCMS (ESI) C 28 H 42 Calculated value for BrN5O3Si2 is 631, measured value is 632 [M+1] + .

[0264] Step 5: 4-amino-2-(4-amino-2-(2-hydroxyethoxy)phenyl)-3-bromo-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile To a solution of 4-(4-amino-6-(4-(2-fluoroacrylamido)-2-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclopropyl-2-methoxybenzamide (1 g, 1.58 mmol, 1.0 equiv) in DCM (15 mL) was added TFA (4 mL). The reaction mixture was stirred at 25° C. for 4 h and then concentrated. The residue was redissolved in MeOH / NH4OH (10 mL / 2 mL) and then stirred at room temperature for 1 h. The reaction mixture was quenched with H2O (50 mL) and filtered to give the product (260 mg) as a grey solid. LCMS (ESI) C 16 H 14 Calculated value for BrN5O2: 387, Found value: 388 [M+1] + .

[0265] Step 6: 3,12-diamino-13-bromo-6,7-dihydrobenzo[f]pyrido[3',4':4,5]pyrrolo[1,2-d][1,4]oxazepine-9-carbonitrile To a solution of 4-amino-2-(4-amino-2-(2-hydroxyethoxy)phenyl)-3-bromo-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile (120 mg, 0.31 mmol, 1.0 equiv.) and PPh3 (240 mg, 0.92 mmol) in THF (20 mL) under the protection of N2, DIAD (280 mg, 1.39 mmol) was added at 0° C. The reaction mixture was stirred at room temperature for 24 h and then concentrated under reduced pressure. The residue was purified by FCC (DCM:MeOH=20:1) to give the product (200 mg, crude) as a yellow oil. LCMS (ESI) C 16 H 12 Calculated for BrNO: 369; Found: 370 [M+1] + .

[0266] Step 7: N-(12-amino-13-bromo-9-cyano-6,7-dihydrobenzo[f]pyrido[3',4':4,5]pyrrolo[1,2-d][1,4]oxazepin-3-yl)acrylamide To a solution of 3,12-diamino-13-bromo-6,7-dihydrobenzo[f]pyrido[3',4':4,5]pyrrolo[1,2-d][1,4]oxazepine-9-carbonitrile (100 mg, 0.27 mmol, 1.0 equiv) in DCM (8 mL) under the protection of N2, acryloyl chloride (74 mg, 0.81 mmol) was added at -20°C. The reaction mixture was stirred at -20°C for 30 min and then concentrated under reduced pressure. The residue was purified by FCC (DCM:MeOH=20:1) to give the product (50 mg, crude) as a white solid. LCMS (ESI) C 19 H 14 Calculated for BrN5O2: 423; Found: 424 [M+1] + .

[0267] Step 8: 4-(3-acrylamido-12-amino-9-cyano-6,7-dihydrobenzo[f]pyrido[3',4':4,5]pyrrolo[1,2-d][1,4]oxazepin-13-yl)-N-(3,3-difluorocyclobutyl)-2-methoxybenzamide To a solution of N-(12-amino-13-bromo-9-cyano-6,7-dihydrobenzo[f]pyrido[3',4':4,5]pyrrolo[1,2-d][1,4]oxazepin-3-yl)acrylamide (45 mg, 0.11 mmol, 1.0 equiv.) and N-(3,3-difluorocyclobutyl)-2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (60 mg, 0.16 mmol, 1.5 equiv.) in DMF / HO (5 / 0.5 mL) was added CsF (32 mg, 0.22 mmol, 2.0 equiv.) and Pd(DtBPF)Cl2 (7 mg, 0.01 mmol, 0.1 equiv.). The reaction mixture was stirred at 50 °C under N2 for 2 h and then concentrated. The residue was purified by FCC (DCM:MeOH=20:1) and Prep-HPLC to give compound 532 (5 mg) as a white solid. LCMS (ESI) C 31 H 26 Calculated for F2N6O4: 584; Found: 585 [M+1] + . 1 H NMR(400MHz,DMSO) δ 10.32(s,1H),8.57(d,J=6.8Hz,1H),8.22(s,1H),7.69(m,2H),7.24-7.22(m,1H),7.07(s,1H),6.97(d,J=8.0Hz,1H),6.86(d,J=8.4Hz,1H), 6.44-6.38(m,1H),6.30-6.24(m,1H),5.80-5.77(m,1H),4.59(s,4H), 4.30-4.26(m,1H),3.79(s,3H),3.00-2.89(m,2H),2.82-2.70(m,2H).

[0268] Examples of the compounds of the present invention include those listed in Table 2 and the examples herein, or pharma- ceutically acceptable salts, prodrugs, solvates, hydrates, tautomers, and isomers thereof. Some of these compounds can be prepared according to the similar methods of Examples 1, 71, 100, 338, 339, or 346, and some of these compounds can be prepared according to the similar methods of Examples 28, 343, 344, 355, 398, 459, 474, 488, 499, 501, or 513. Some of these compounds can also be prepared with reference to the above examples or combinations thereof.

[0269] [Table 2(1)] [Table 2(2)] [Table 2(3)] [Table 2(4)] [Table 2(5)] [Table 2(6)] [Table 2(7)] [Table 2(8)] [Table 2(9)] [Table 2 (10)] [Table 2(11)] [Table 2 (12)]

Table 2(13)

Table 2(14)

Table 2(15)

Table 2(16)

Table 2(17)

Table 2(18)

Table 2(19)

Table 2(20)

Table 2(21)

Table 2(22)

Table 2(23)

Table 2(24)

Table 2(25)

Table 2(26)

Table 2(27)

Table 2(28)

Table 2(29)

Table 2(30)

Table 2(31)

Table 2(32)

Table 2(33)

Table 2(34)

Table 2(35)

Table 2(36)

Table 2(37)

Table 2(38)

Table 2(39)

Table 2(40)

Table 2(41)

Table 2(42)

Table 2(43)

Table 2(44)

Table 2(45)

Table 2(46)

Table 2(47)

Table 2(48)

Table 2(49)

Table 2(50)

Table 2(51)

Table 2(52)

Table 2(53)

Table 2(54)

Table 2(55)

Table 2(56)

Table 2(57)

Table 2(58)

Table 2(59)

Table 2(60)

Table 2(61)

Table 2(62)

Table 2(63)

Table 2(64)

Table 2(65)

Table 2(66)

Table 2(67)

Table 2(68)

Table 2(69)

Table 2(70)

Table 2(71)

Table 2(72)

Table 2(73)

Table 2(74)

Table 2(75)

Table 2(76)

Table 2(77)

Table 2(78)

Table 2(79)

Table 2(80)

Table 2(81)

Table 2(82)

Table 2(83)

Table 2(84)

Table 2(85)

Table 2(86)

Table 2(87)

Table 2(88)

Table 2(89)

Table 2(90)

Table 2(91)

Table 2(92)

Table 2(93)

Table 2(94)

Table 2(95)

[0270] Some compounds of the present invention are listed in Table 3.

[0271] [Table 3(1)] [Table 3(2)] [Table 3(3)] [Table 3(4)] [Table 3(5)] [Table 3(6)] [Table 3(7)]

[0272] Biochemical and Cellular Activity Example A: Biochemical Caliper Assay Compounds of the invention were tested in the FGFR1, FGFR2, and FGFR3 biochemical Caliper assays.

[0273] Enzyme activity was monitored using KinEASE-TK kit (CisBio, Cat. No. 62TK0PEC) according to the manufacturer's instructions. Proteins were purchased from Carna (FGFR1, Cat. No. 08-133; FGFR2, Cat. No. 08-134; FGFR3, Cat. No. 08-135). Final enzyme concentrations were 0.2 nM for FGFR1 and FGFR3, and 0.07 nM for FGFR2. Compounds were prepared in 10 mM DMSO and serially diluted to 10 concentrations by 3-fold dilutions. Compounds were incubated with protein for 10 min at room temperature before initiating the reaction by adding TK-substrate / ATP mixture. Reactions were allowed to proceed for 45 min at room temperature. Plates were quenched by adding TK-antibody-cryptate and Sa-XL665 mixture. After 60 min in stop solution, the signal was read on a microplate reader (Molecular Devices, i3x), excitation at 320 nm and emission at 615 nm and 665 nm with a delay of 90 μs. IC50 values ​​were calculated using Prism 7 (GraphPad).

[0274] The results of the FGFR2 biochemical caliper assay and the selectivity of FGFR1 / FGFR2 and FGFR3 / FGFR2 are shown in Table 4.

[0275] Compounds having an FGFR2 IC50 of 5 nM or less are designated "A+", compounds having an FGFR2 IC50 of greater than 5 nM and less than or equal to 10 nM are designated "A", and compounds having an FGFR2 IC50 of greater than 10 nM are designated "B".

[0276] Compounds with FGFR1 / FGFR2 selectivity of 500 or more are designated "A+", compounds with FGFR1 / FGFR2 selectivity of 300 or more and less than 500 are designated "A", compounds with FGFR1 / FGFR2 selectivity of 200 or more and less than 300 are designated "B", and compounds with FGFR1 / FGFR2 selectivity of 100 or more and less than 200 are designated "C".

[0277] Compounds with FGFR3 / FGFR2 selectivity of 150 or more are designated "A+", compounds with FGFR3 / FGFR2 selectivity of 100 or more and less than 150 are designated "A", and compounds with FGFR3 / FGFR2 selectivity of 25 or more and less than 100 are designated "B".

[0278] Example B: Cell line proliferation assay Compounds of the invention were also tested in the SNU16 cancer cell line proliferation assay.

[0279] SNU16 cells were seeded in 96-well clear bottom / white plates (Costar, Cat. No. 3610) at 5000 cells / well in 100 μl medium. Test compounds were prepared in 10 mM DMSO stock solutions and serially diluted to nine concentrations by 3-fold dilutions. 0.5 μl of each concentration of compound was added to the cell culture plate, and DMSO was added as a control. The plates were incubated in an incubator at 37° C. and 5% CO2 for 72 hours. 50 μl of CellTiter-Glo reagent (Promega, G7572) was added to each well, and then the plates were gently shaken at room temperature for 10 minutes. Luminescence was read on a microplate reader (Molecular Devices, i3x) and IC50 values ​​were calculated using Prism7 (GraphPad).

[0280] The results of the SNU16 cancer cell line proliferation assay are shown in Table 4.

[0281] Compounds having an IC50 of 10 nM or less are designated "A+", compounds having an IC50 of greater than 10 nM and less than or equal to 50 nM are designated "A", and compounds having an IC50 of greater than 50 nM are designated "B".

[0282] [Table 4(1)] [Table 4(2)] [Table 4(3)] 0* Compound 0 is disclosed in a PCT application having International Publication Number WO2020 / 231990A1, and the chemical name of compound 0 is N-(4-(4-amino-5-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)phenyl)methacrylamide.

[0283] Example C: Pharmacokinetics in SD rats Animal studies were performed according to protocols approved by the Institutional Animal Care and Use Committee of INVIVO Biotech Co., Ltd.

[0284] Animal information: Sprague-Dawley (SD) rats, SPF, 6-8 weeks old, male, weighing 200-250g, were purchased from Beijing Vital River Lab (Beijing, People's Republic of China). Formulations: 1.5 mg / ml and 0.6 mg / ml solutions of compound in 5% DMSO+10% Solutol+85% HPβCD (20% HPβCD) are prepared for PO and IV use, respectively, and administered immediately after preparation. Administration: PO and IV; Dose: 15 mg / kg PO and 3 mg / kg IV;

[0285] Plasma was collected at 0.083, 0.25, 0.5, 1, 2, 4, 6, 8, and 24 hours after dosing and analyzed via LC-MS / MS Analyst and Winnonlin to determine PK parameters (T 1 / 2 , C max and AUC 0-∞ , and calculate the clearance (Cl) (IV). PK results are shown in Table 5.

[0286] [Table 5] 0* Compound 0 is disclosed in a PCT application having International Publication Number WO2020 / 231990A1, and the chemical name of compound 0 is N-(4-(4-amino-5-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)phenyl)methacrylamide.

[0287] Incorporation by Reference All publications and patents mentioned in this specification are hereby incorporated by reference in their entirety for all purposes to the same extent as if each individual publication or patent was specifically and individually indicated to be incorporated by reference. In case of conflict, the present application, including any definitions herein, will control.

[0288] Equivalent While specific embodiments of the present disclosure have been discussed, the above specification is illustrative and not restrictive. Many variations of the present disclosure will become apparent to those skilled in the art upon review of this specification. The full scope of the present disclosure should be determined by reference to the claims, including their full scope of equivalents, and by reference to the specification, including such variations.

[0289] Unless otherwise indicated, all numbers expressing quantities of ingredients, reaction conditions, and so forth used in the specification and claims are to be understood as being modified in all instances by the term "about." Accordingly, unless otherwise indicated, the numerical parameters set forth in the specification and appended claims are approximations that may vary depending upon the desired properties sought to be obtained by the present disclosure.

Claims

1. A compound represented by formula (I) 【Chemical 1】 or a pharmaceutically acceptable salt, prodrug, solvate, hydrate, tautomer, and isomer thereof, provided that in the formula,[[]] ring A is 【Chemical Formula 2】 selected from 【Chemical Formula 3】 represents a bond to ring D,[[]] [Chemical Formula 4] represents a bond to ring B,[[]] R ａ Each of which is independently H, D, CN, NH ２ , OH, halogen, C １～６ alkyl, C ３～６ cycloalkyl, C １～６ alkoxyl, -(CH ２ ) ０～２ -NHR', -(CH ２ ) ０～２ N(R') ２ , or may be independently selected from a 3- to 6-membered saturated heterocyclic ring having 1 or 2 heteroatoms which may be independently selected from N, O or S, and each of these may be independently unsubstituted or substituted with 1, 2 or 3 examples of D, OH, halogen, C １～３ alkyl, or C １～３ may be substituted with alkoxyl, R ａ ' is CN, or R ａ and R ａ ’ together with their intervening atoms form a 5- to 7-membered heterocyclic ring having at least one nitrogen atom, each of which is independently unsubstituted or substituted with 1, 2, or 3 examples of C １～３ alkoxy, C １～３ alkyl, D or halogen and may be substituted Ring B is phenylene; a divalent saturated or partially unsaturated 3- to 10-membered carbocyclic ring; a divalent saturated or partially unsaturated 3- to 10-membered heterocyclic ring having 1 to 5 heteroatoms independently selected from N, O, S, S(O), S(O) ２ , S(O)(NH), or S(O)(NC １～３ alkyl); or a 5- to 10-membered heteroarylene having 1 to 5 heteroatoms or groups independently selected from N, O, or S, each of which is independently unsubstituted or substituted in addition to -L ｂ -R ｂ with R in the r examples, Ｂ where r is 0, 1, 2, 3, or 4. Ring D is phenylene; a divalent saturated or partially unsaturated 3- to 10-membered carbocyclic ring; a divalent saturated or partially unsaturated 3- to 10-membered heterocyclic ring having 1 to 5 heteroatoms independently selected from N, O, S, S(O), S(O) ２ , S(O)(NH), or S(O)(NC １～３ alkyl); or a 5- to 10-membered heteroarylene having 1 to 5 heteroatoms independently selected from N, O, or S, each of which is independently unsubstituted or, in addition to -L ｄ -R ｄ is optionally substituted with an example of R Ｄ where u is 0, 1, 2, 3, or 4 R Ｂ or R Ｄ each of which is independently, -D, oxo, -OH, -NH ２ , -CN, -NO ２ , -(CH ２ ) ０～２ NHR', -(CH ２ ) ０～２ N(R')[[]] ２ , -(CH ２ ) ０～２ OR', R, -SO ２ R, or -COR, and may be selected from,​ L ｂ and L ｄ each independently may be selected from a covalent bond, -O-, -S-, -NHS(O)-, ２ -, -S(O)-, S(O) ２ -, -CO-, -NH-, -(CH ２ ) １～３ , -CONH-, -C(S)NH-, -NHCO-, -CONH(CH ２ ) １～３ -, -NHCO(CH ２ ) １～３ -, or -NHCONH-, and each CH ２ independently may be unsubstituted or substituted with 1, 2 or 3 instances of D, halogen, C １～３ alkyl, or C １～３ haloalkyl, and each NH independently may be unsubstituted or substituted with C １～３ alkyl. R ｂ is halogen, CN, [Chemical Formula 5] and R ｂ１ 、 R ｂ２ 、 and R ｂ３ each independently may be selected from H, D, halogen, -CN, C １～６ alkyl, C ３～６ cycloalkyl, C ２～６ alkenyl, C ２～６ alkynyl, -(CH ２ ) ０～２ NHR', -(CH ２ ) ０～２ N(R')[[]] ２ , or -(CH ２ ) ０～２ OR', and each of these may independently be unsubstituted or substituted with 1, 2, or 3 examples of halogen or D, or R ｂ１ and R ｂ２ , R ｂ２ and R ｂ３ , R ｂ１ and L ｂ together with their intervening atoms form a 4- to 7-membered saturated or partially unsaturated ring having from 0 to 2 heteroatoms or groups selected from N, O, S, S(O), or S(O) ２ 2, and R ｄ is H; D; C １～６ alkyl; phenyl; a saturated or partially unsaturated 3- to 10-membered carbocyclic ring; a saturated or partially unsaturated 3- to 10-membered heterocyclic ring having 1 to 5 heteroatoms independently selected from N, O, S, S(O), or S(O) ２ ; or a 5- to 10-membered heteroaryl having 1 to 5 heteroatoms or groups independently selected from N, O, or S, each of which is independently unsubstituted or may be substituted with 1, 2, or 3 examples of R Each of R is independently halogen, -CN, -C １～６ alkyl, -C ３～６ cycloalkyl, -SC １～６ alkyl, -N(C １～６ alkyl) ２ , -NHC １～６ alkyl, -NHC ３～６ cycloalkyl, -C １～６ alkoxy or -OC ３～６ cycloalkyl, and each of these may be unsubstituted or substituted with 1, 2, or 3 examples of D or halogen. Each of R' is independently C １～６ alkyl or C ３～６ cycloalkyl, or may be selected from The two R's, together with the nitrogen to which both are attached, may form a 4- to 6-membered heterocyclic ring having one or two additional heteroatoms or groups selected from N, O, S, S(O), or S(O) ２ ２ the compound, or a pharmaceutically acceptable salt, prodrug, solvate, hydrate, tautomer, and isomer thereof.

2. The compound according to claim 1, wherein the compound is represented by formula (IV) or a pharmaceutically acceptable salt thereof. 【Chemical Formula 6】

3. Said R ａ is, independently, H, D, CN, NH ２ , OH, F, methyl, cyclopropyl, cyclobutyl, -NHR', -CH ２ NHR', -(CH ２ ) ２ NHR', -N(R') ２ , -CH ２ N(R') ２ , -(CH ２ ) ２ N(R') ２ may be selected from a 4-membered saturated heterocyclic ring, a 5-membered saturated heterocyclic ring, or a 6-membered saturated heterocyclic ring, and further, each of the heterocyclic rings may independently have 1 or 2 heteroatoms selected from N or O, and each of these may independently be unsubstituted or substituted with 1, 2 or 3 examples of D, OH, or F. The compound according to claim 1 or a pharmaceutically acceptable salt thereof.

4. said R ａ each of which 【Chemical Formula 7】 The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein

5. The ring B is phenylene; a divalent saturated 5- or 6-membered heterocyclic ring having one or two heteroatoms independently selected from N; or a 5- or 6-membered heteroarylene having one or two heteroatoms independently selected from N, each of which is independently unsubstituted or -L ｂ -R ｂ In addition to the R of the r example Ｂ The compound according to claim 1 or a pharmaceutically acceptable salt thereof, which may be substituted with

6. ring B is phenylene,[[]] 【Chemical 8】 and 【Chemical Formula 9】 Each of which can optionally be bonded to ring A or -L ｂ -R ｂ and each of these can independently be unsubstituted or, in addition to -L ｂ -R ｂ optionally substituted with R in the r examples Ｂ The compound according to claim 1 or a pharmaceutically acceptable salt thereof, which may be substituted with

7. The ring D is phenylene; a divalent saturated 5- or 6-membered heterocyclic ring having one or two heteroatoms independently selected from N; or a 5- or 6-membered heteroarylene having one or two heteroatoms independently selected from N, each of which is independently unsubstituted or -L ｄ -R ｄ In addition to the u example of R Ｄ The compound according to claim 1 or a pharmaceutically acceptable salt thereof, which may be substituted with

8. each of ring D is phenylene; 【Chemical Formula 10】 The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein

9. each of RB is independently 【Chemical 11】 The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein

10. Said R Ｄ each independently is H, D, F, Cl, CN, OH, methyl, ethyl, propyl, cyclopropyl, -SMe, -OMe, -OEt, -CFH ２ , -CF ２ H 、 -CF ３ selected from, and each of these is independently unsubstituted or may be substituted with 1, 2 or 3 examples of F, Cl, or D, the compound according to claim 1 or a pharmaceutically acceptable salt thereof.

11. Said L ｂ and L ｄ each may independently be selected from a covalent bond, -O-, -S-, -CO-, -NH-, -CONH-, -NHCO-, and each of these may independently be unsubstituted or substituted with 1, 2 or 3 examples of D, F, Cl, methyl, methoxy, methyl substituted with F or Cl, or methoxy substituted with F or Cl. The compound according to claim 1 or a pharmaceutically acceptable salt thereof.

12. The said R ｂ is 【Chemical Formula 12】 The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein

13. Said R ｂ１ , R ｂ２ , and R ｂ３ each may independently be selected from H, D, F, Cl, -CN, methyl, ethyl, propyl, i-propylvinyl, ethynyl, or ethynyl, and each of these may independently be unsubstituted or substituted with 1, 2 or 3 examples of F, Cl, or D. The compound according to claim 1 or a pharmaceutically acceptable salt thereof.

14. The foregoing R ｄ is H; D; methyl; ethyl; phenyl; a 5- or 6-membered monocyclic heteroaryl ring having 1 or 2 heteroatoms independently selected from N or S; a 3-, 4-, 5- or 6-membered saturated carbocyclic ring; a 4-, 5- or 6-membered saturated monocyclic heterocyclic ring having 1 or 2 heteroatoms independently selected from N; or a 5-, 6- or 7-membered saturated bicyclic carbocyclic ring, each of which is independently unsubstituted or may be substituted with 1, 2 or 3 examples of R, the compound according to claim 1 or a pharmaceutically acceptable salt thereof.

15. The aforesaid R ｄ is 【Chemical 13】 and each of these is independently unsubstituted or may be substituted with 1, 2, or 3 examples of R. The compound according to claim 1 or a pharmaceutically acceptable salt thereof.

16. Each said R is independently F, Cl, Br, C １～３ alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, -SC １～３ alkyl, -N(C １～３ alkyl), ２ , -NHC １～３ alkyl, -NH-cyclopropyl, -NH-cyclobutyl, -NH-cyclopentyl, -NH-cyclohexyl, -C １～３ alkoxy, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl, or -O-cyclohexyl, each of which may be unsubstituted or substituted with 1, 2 or 3 examples of D, F, Cl, or Br, the compound according to claim 1 or a pharmaceutically acceptable salt thereof.

17. R may be independently selected from F, Cl, methyl, ethyl, methoxy, or cyclopropyl, and each of these may be unsubstituted or may be substituted with 1, 2, or 3 examples of D or F. The compound according to claim 1 or a pharmaceutically acceptable salt thereof.

18. Represented by formula (I-I) or formula (I-II), 【Chemical 14】 wherein R ２１ is selected from H, D, CN, C １～３ alkyl, C １～３ alkoxyl, C ３～６ cycloalkyl, -(CH ２ ) ０～２ -NHC １～３ alkyl, -(CH ２ ) ０～２ N(C １～３ alkyl) ２ or is selected from a 3- to 6-membered saturated heterocyclic ring having one or two heteroatoms which may be independently selected from N, O or S, each of which is independently unsubstituted or substituted with 1, 2 or 3 examples of D, OH, halogen, C １～３ alkyl, C １～３ alkoxyl, or C ３～６ cycloalkyl and may be substituted, R ２２ Each of which is independently H, D, halogen, CN, NH ２ , OH, C １～３ alkyl, C １～３ alkoxyl, C ３～６ cycloalkyl, -(CH ２ ) ０～２ -NHC １～３ alkyl, or -(CH ２ ) ０～２ N(C １～３ alkyl) ２ and may each independently be unsubstituted or substituted with 1, 2 or 3 examples of R ｚ or R ２１ and R ２２ together with their intervening atoms form a 5- to 7-membered heterocyclic ring having at least one nitrogen atom, R ２５ Each of which is independently H, D, halogen, CN, OH, R'', N(R'') ２ , OR'', or -SR'' and may be y is 0, 1, 2, 3, or 4,[[]] Each of X or L is independently a covalent bond, -O-, -S-, -S(O)-, -NHS(O) ２ -, -S(O) ２ -, -CO-, -NH-, -CH ２ -, -CONH-, -NHCO-, -CONHCH ２ -, -NHCONH-, -NHCOCH ２ -, or -NHCOCH ２ CH ２ - and may be selected from, each of CH ２ is independently unsubstituted or substituted with 1, 2 or 3 examples of D, halogen, C １～３ alkyl, or C １～３ haloalkyl, and each of NH is independently unsubstituted or substituted with C １～３ alkyl and may be 【Chemical Formula 15】 is a divalent bond or a trivalent bond,[[]] １） 【Chemical Formula 16】 When it is a trivalent bond, each of R ２３ does not exist, and each of R ２４ is independently selected from H, D, -C ０～３ alkylene-N(R"), ２ -C ０～３ alkylene-OR", or R", and each of these may be unsubstituted or substituted with 1, 2 or 3 examples of D or halogen. ２） 【Chemical 17】 When it is a divalent bond, R ２３ or R ２４ each of which is independently H, D, halogen, -C ０～３ alkylene-N(R'' ２ ), -C ０～３ alkylene-OR'', or R'', and each of these may be unsubstituted or substituted with 1, 2 or 3 examples of D or halogen. Each of W is independently C １～３ It may be selected from an alkyl, phenyl, a 4- to 6-membered saturated or partially saturated heterocyclic ring having one or two heteroatoms selected from N, O, or S, a 5- or 6-membered heteroaryl having one to three heteroatoms selected from N, O, or S, or a 3- to 6-membered saturated or partially saturated carbocyclic ring, and each of these may independently be unsubstituted or substituted with one, two or three examples of R ｗ and may be substituted. R ｗ Each of them is independently selected from D, halogen, OH, CN, NH ２ , C １～３ alkyl, C １～３ haloalkyl, C ３～６ cycloalkyl, C ２～３ alkenyl or C ２～３ alkynyl, and each of these may be independently unsubstituted or substituted with 1, 2 or 3 examples of R ｚ and may be substituted, R ｚ Each of which is independently selected from H, D, halogen, CN, -N(R'' ２ ), -OR'', or R'' and may be selected. Each of "R" is independently C １～３ alkyl, or C ３～６ cycloalkyl, each of which may be unsubstituted or substituted with 1, 2 or 3 examples of halogen or D a compound or a pharmaceutically acceptable salt thereof.

19. The aforesaid R ２１ is 【Chemical Formula 18】 selected from, said R ２２ is 【Chemical Formula 19】 The compound according to claim 18 or a pharmaceutically acceptable salt thereof, wherein

20. R ２５ Each of which may independently be H, D, F, Cl, methyl, ethyl, -S-methyl, -S-ethyl, methoxy, or ethoxy, each of which may be unsubstituted or substituted with 1, 2 or 3 examples of D or F, the compound according to claim 18 or a pharmaceutically acceptable salt thereof.

21. Each of said X or L may independently be selected from a covalent bond, -O-, -CO-, -NH-, -CH ２ - , -CONH- , or -NHCO-; the compound according to claim 18, or a pharmaceutically acceptable salt thereof.

22. said 【Chemical 20】 is a divalent bond, and said R ２３ or R ２４ each independently may be selected from H, D, F, Cl, methyl, ethyl, propyl, i-propyl, or cyclopropyl, each of which may be unsubstituted or substituted with 1, 2 or 3 examples of D, F or Cl. The compound according to claim 18 or a pharmaceutically acceptable salt thereof.

23. W may be independently selected from a 5- or 6-membered saturated heterocyclic ring having 1 nitrogen atom, a 5-membered heteroaryl having 1 nitrogen atom and optionally further 1 sulfur atom, a 6-membered heteroaryl having 1 or 2 nitrogen atoms, a 3-membered saturated carbocyclic ring, a 4-membered saturated carbocyclic ring, a 5-membered saturated carbocyclic ring, or a 6-membered saturated carbocyclic ring. The compound according to claim 18 or a pharmaceutically acceptable salt thereof.

24. Said R ｗ each of which may independently be selected from D; F; Cl; methyl; methyl substituted with 1, 2 or 3 examples of F or D; methoxy; or cyclopropyl, the compound according to claim 18 or a pharmaceutically acceptable salt thereof.

25. N-(4-(3-(3-Methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)imidazo[1,2-b]pyridazin-2-yl)phenyl)acrylamide; N-(4-(9-(3-Methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-9H-purin-8-yl)phenyl)acrylamide; N-(4-(7-(3-Methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)imidazo[1,2-b][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-3-(3-Methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)phenyl)acrylamide; N-(4-(5-Amino-3-(3-Methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)imidazo[1,2-a]pyrimidin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-5-cyano-3-(3-Methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[2,3-b]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(3-Methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(3-Methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-2,7-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-2-chloro-5-(3-Methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)phenyl)acrylamide; N-(4-(4-Methoxy-5-(3-Methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)phenyl)acrylamide; N-(4-(4-Cyclopropyl-5-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)phenyl)acrylamide; N-(4-(4-(Difluoromethoxy)-5-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)phenyl)acrylamide; N-(4-(4-Cyano-5-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-6-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(4-(pyrrolidine-1-carbonyl)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-Amino-5-(3-methoxy-4-((5-(methylamino)pyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(3-methoxy-4-(pyrrolidine-1-carbonyl)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(3-methoxy-4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(4-(pyrimidin-2-yloxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; 2-(4-Acrylamidophenyl)-4-amino-3-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridine-7-carboxamide; N-(4-(4-Amino-7-cyano-3-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; 4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclopropyl-2-methoxybenzamide; 4-(6-(4-Acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-(difluoromethoxy)-N-((1r,3r)-3-fluorocyclobutyl)benzamide; (S)-4-(6-(4-Acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-fluoro-N-(tetrahydrofuran-3-yl)benzamide; 4-(6-(4-Acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclobutyl-2-methoxybenzamide; 4-(4-Amino-6-(4-methacrylamidophenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-isobutylbenzamide; N-(4-(4-Amino-5-(3-methoxy-4-(pyrimidin-2-yloxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(3-fluoro-4-(pyrimidin-2-yloxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(4-phenoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(4-(pyridin-2-yloxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(4-(cyclopentyloxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(4-(pyrimidin-2-yloxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)-2-fluorophenyl)acrylamide; N-(4-(4-Amino-5-(4-(pyrimidin-2-yloxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)-3-fluorophenyl)acrylamide; 4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-(2-hydroxyethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclobutyl-2-methoxybenzamide; 4-(6-(4-Acrylamidophenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-isobutylbenzamide; 4-(6-(4-Acrylamidophenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclobutylbenzamide; 4-(6-(4-Acrylamidophenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclobutyl-2-fluorobenzamide; Methyl 4-(6-(4-acrylamidophenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxybenzoate; 4-(6-(4-Acrylamidophenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(6-(4-Acrylamidophenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(oxetan-3-yl)benzamide; 4-(6-(4-Acrylamidophenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-((1-methyl-1H-pyrazol-3-yl)methyl)benzamide; 4-(6-(4-Acrylamidophenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(cyclobutylmethyl)-2-methoxybenzamide; 4-(6-(4-Acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-((1s,3s)-3-hydroxycyclobutyl)-2-methoxybenzamide; 4-(6-(4-Acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-((1-cyanocyclopropyl)methyl)-2-methoxybenzamide; 4-(4-Amino-6-(4-(2-fluoroacrylamido)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-isobutylbenzamide; 4-(6-(4-Acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclobutyl-2-methoxy-N-methylbenzamide; 4-(6-(4-Acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclobutylcyclohex-3-ene-1-carboxamide; 4-(6-(4-Acrylamido-3-fluorophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-isobutylbenzamide; 4-(6-(4-Acrylamido-2-fluorophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-isobutylbenzamide; 4-(6-(4-Acrylamido-3-methoxyphenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-isobutylbenzamide; 4-(6-(4-Acrylamido-2-methoxyphenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-isobutylbenzamide; 4-(6-(4-Acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclopentyl-2-methoxybenzamide; 4-(6-(4-Acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2-methoxy-2-methylpropyl)benzamide; 4-(6-(4-Acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(2-hydroxy-2-methylpropyl)-2-methoxybenzamide; 4-(6-(4-Acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclohexyl-2-methoxybenzamide; 4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-(2-methoxyethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclobutyl-2-methoxybenzamide; 4-(6-(4-Acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-ethyl-2-methoxybenzamide; 4-(6-(4-Acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-isopropyl-2-methoxybenzamide; 4-(6-(4-Acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(2-(dimethylamino)ethyl)-2-methoxybenzamide; 4-(6-(4-Acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-((1s,3s)-3-methoxycyclobutyl)benzamide; 4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-isobutyl-2-methoxybenzamide; 4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclobutylbenzamide; 4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclobutyl-2-methoxybenzamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-(pyrimidin-2-yloxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(3-methoxy-4-(pyrimidin-2-yloxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; 4-(4-Amino-6-(4-methacrylamidophenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; (E)-4-(4-Amino-6-(4-(4-(dimethylamino)but-2-enamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(6-(4-Acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclobutyl-2-(trifluoromethoxy)benzamide; 4-(6-(4-Acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclobutyl-2-methylbenzamide; 4-(6-(4-Acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclobutyl-2-ethoxybenzamide; 4-(6-(4-Acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclobutyl-2-methoxy-5-methylbenzamide; 4-(4-Amino-6-(4-(2-(trifluoromethyl)acrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-Amino-6-(4-(N-methylacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(6-(4-Acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-methyl-N-(2,2,2-trifluoroethyl)benzamide; N-(4-(4-Amino-5-(3-methoxy-4-(4-(trifluoromethyl)oxazol-2-yl)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; 4-(6-(4-Acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-isobutyl-2-methoxybenzamide; N-(4-(4-Amino-5-(2,2-dimethyl-4-oxo-3,4-dihydro-2H-benzo[e][1,3]oxazin-7-yl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(5-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepin-8-yl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; 4-(6-(4-Acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclobutyl-2-methoxy-6-methylbenzamide; 4-(6-(4-Acrylamido-2-methoxyphenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(6-(4-Acrylamido-2-fluorophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(6-(4-Acrylamido-2-methylphenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(6-(2-Acryloyl-2-azaspiro[3.3]heptan-6-yl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(6-(4-Acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclopropyl-2-methoxybenzamide; 4-(6-(6-Acrylamidopyridin-3-yl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(6-(4-Acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-(difluoromethoxy)-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-Amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-methyl-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-Amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclopentyl-2-methoxybenzamide; 4-(4-Amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-ethyl-2-methoxybenzamide; 4-(4-Amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclobutyl-2-methoxybenzamide; 4-(4-Amino-7-cyano-2-(4-(2-fluoroacrylamide)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclobutylbenzamide; 4-(6-(4-Acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(3,3-difluorocyclobutyl)-2-methoxybenzamide; 4-(4-Amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(3,3-difluorocyclobutyl)-2-methoxybenzamide; 4-(4-Amino-6-(4-(2-fluoroacrylamide)-2-methylphenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-Amino-6-(4-(2-fluoroacrylamide)-2-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-Amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclopropyl-2-methoxybenzamide; 4-(4-Amino-7-cyano-2-(4-(2-fluoroacrylamide)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclopropyl-2-methoxybenzamide; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclopropyl-2-methoxybenzamide; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-(2,2,2-trifluoroethyl)benzamide; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-ethyl-2-methoxybenzamide; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-isopropyl-2-methoxybenzamide; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclopentyl-2-methoxybenzamide; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclohexyl-2-methoxybenzamide; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-((1-cyanocyclopropyl)methyl)-2-methoxybenzamide; 4-(2-(4-Acrylamido-2-methoxyphenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 5-(4-Acrylamidophenyl)-4-(3-methoxy-4-((6-methylpyridin-2-yl)oxy)phenyl)nicotinamide; 5-(4-Acrylamidophenyl)-2-amino-4-(3-methoxy-4-((6-methylpyridin-2-yl)oxy)phenyl)-6-methylnicotinamide; N-(4-(4-Amino-3-(3-methoxy-4-((6-methylpyridin-2-yl)oxy)phenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-3-(3-methoxy-4-((6-methylpyridin-2-yl)oxy)phenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)methacrylamide; 1-(3-((4-Amino-5-(3-methoxy-4-((6-methylpyridin-2-yl)oxy)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)piperidin-1-yl)prop-2-en-1-one; N-(4-(4-Amino-3-(3-methoxy-4-((6-methylpyridin-2-yl)oxy)phenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)-2-fluorophenyl)acrylamide; 5-(4-Acrylamidophenyl)-2-amino-4-(3-methoxy-4-((6-methylpyridin-2-yl)oxy)phenyl)-6-methylnicotinamide; 4-(4-Amino-2-(4-methacrylamidophenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-3-yl)-N-isobutylbenzamide; 4-(2-(4-Acrylamidophenyl)-4-amino-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-3-yl)-N-isobutylbenzamide; N-(4-(4-Cyano-6-(3-methoxy-4-((6-methylpyridin-2-yl)oxy)phenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)phenyl)acrylamide; N-(4-(4-Chloro-6-(3-methoxy-4-((6-methylpyridin-2-yl)oxy)phenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)phenyl)acrylamide; N-(4-(4-Methoxy-6-(3-methoxy-4-((6-methylpyridin-2-yl)oxy)phenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)phenyl)acrylamide; 4-(2-(4-Acrylamidophenyl)-4-amino-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-3-yl)-N-cyclobutylbenzamide; N-(4-(4-Amino-7-oxo-3-(4-(pyrrolidine-1-carbonyl)phenyl)-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; 4-(2-(4-Acrylamidophenyl)-4-amino-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-3-yl)-N-(oxetan-3-yl)benzamide; N-(4-(4-Amino-3-(3-methoxy-4-((6-methylpyridin-2-yl)oxy)phenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-Amino-3-(4-(cyclopentyloxy)phenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; 4-(2-(4-Acrylamidophenyl)-4-amino-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-3-yl)-N-(pyrrolidin-3-yl)benzamide; 4-(2-(4-Acrylamidophenyl)-4-amino-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-3-yl)-N-(tetrahydro-2H-pyran-3-yl)benzamide; 4-(2-(4-Acrylamidophenyl)-4-amino-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-3-yl)-N-cyclobutyl-2-methoxybenzamide; N-(4-(4-Amino-3-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)methacrylamide; N-(4-(4-Amino-3-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; 4-(2-(4-Acrylamidophenyl)-4-amino-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-3-yl)-N-isobutyl-2-methoxybenzamide; N-(4-(4-Amino-3-(4-((4-chloropyrimidin-2-yl)oxy)-3-methoxyphenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; 4-(4-Amino-2-(4-(2-fluoroacrylamide)phenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-3-yl)-N-cyclobutyl-2-methoxybenzamide; N-(4-(4-Amino-3-(4-(cyclopentyloxy)-3-methoxyphenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-3-(4-cyclobutoxyphenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-3-(4-(cyclohexyloxy)phenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-3-(4-isobutoxyphenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-3-(4-(cyclopentyloxy)-3-fluorophenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; 5-(4-Acrylamidophenyl)-6-(3-methoxy-4-((6-methylpyridin-2-yl)oxy)phenyl)-1H-indazole-7-carboxamide; N-(4-(4-Amino-7-oxo-3-(4-((tetrahydro-2H-pyran-4-yl)oxy)phenyl)-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-3-(6-(cyclohexyloxy)pyridin-3-yl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-3-(4-(cyclohexyl(methyl)amino)phenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-3-(4-((4,4-difluorocyclohexyl)oxy)phenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-3-(4-(cyclohexylthio)phenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-3-(4-(cyclopentyloxy)phenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)methacrylamide; 4-(2-(4-Acrylamido-2-fluorophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-Amino-7-cyano-2-(2-fluoro-4-(2-fluoroacrylamido)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-Amino-6-(4-(2-fluoroacrylamide)-2-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclopropyl-2-methoxybenzamide; 4-(4-Amino-6-(2-fluoro-4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclopropyl-2-methoxybenzamide; 4-(6-(4-Acrylamide-2-methoxyphenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclopropyl-2-methoxybenzamide; 4-(6-(4-Acrylamide-2-fluorophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclopropyl-2-methoxybenzamide; 4-(2-(4-Acrylamide-2-methoxyphenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclopropyl-2-methoxybenzamide; 4-(2-(4-Acrylamide-2-fluorophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclopropyl-2-methoxybenzamide; 4-(4-Amino-7-cyano-2-(4-(2-fluoroacrylamide)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-isopropyl-2-methoxybenzamide; (S)-4-(4-Amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(3,3-difluorocyclopentyl)-2-methoxybenzamide; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-fluoro-N-(2,2,2-trifluoroethyl)benzamide; N-(4-(4-Amino-7-cyano-3-(4-(cyclopentyloxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; 4-(6-(4-Acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(1-methylcyclopropyl)benzamide; 4-(4-Amino-6-(4-(2-fluoroacrylamido)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(cyclopropylmethyl)-2-methoxybenzamide; N-(4-(4-Amino-5-(4-(cyclopentyl(methyl)amino)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(4-cyclobutoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; 4-(4-Amino-6-(6-ethynylpyridin-3-yl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-(2,2-difluorocyclopropyl)-2-methoxybenzamide; 4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-(3-fluorocyclobutyl)-2-methoxybenzamide; 4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(1-methylcyclopropyl)benzamide; 4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-(cyclopropylmethyl)-2-methoxybenzamide; 4-(4-Amino-7-cyano-2-(4-(2-fluoroacrylamido)-2-methoxyphenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclopropyl-2-methoxybenzamide; N-(4-(4-Amino-3-(4-cyclopropoxyphenyl)-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-3-(4-(((3-fluorocyclopentyl)oxy)phenyl))-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-3-(4-(((3,3-difluorocyclopentyl)oxy)phenyl))-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-3-(4-(((3-methylcyclohexyl)oxy)phenyl))-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-3-(4-hydroxyphenyl))-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-3-(4-(methoxymethoxy)phenyl))-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-3-(1-(3,3-difluorocyclopentyl)-1H-indol-5-yl))-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; 4-(4-Amino-6-(6-ethynyl-4-methylpyridin-3-yl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-Amino-7-cyano-2-(6-ethynylpyridin-3-yl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-Amino-7-cyano-2-(6-ethynylpyridin-3-yl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclopropyl-2-methoxybenzamide; N-(4-(4-Amino-5-(4-(cyclopentyloxy)-3-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; 4-(4-Amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxybenzamide; 4-(6-(4-Acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(3-fluorocyclobutyl)-2-methoxybenzamide; 4-(4-Amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(3-fluorocyclobutyl)-2-methoxybenzamide; 4-(4-Amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(1-methylcyclopropyl)benzamide; 4-(6-(4-Acrylamido-2-chlorophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclopropyl-2-methoxybenzamide; 4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-(3,3-difluorocyclobutyl)-2-methoxybenzamide; 4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-(2-fluoroethyl)-2-methoxybenzamide; N-(4-(4-Amino-7-cyano-3-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(3-methoxy-4-((6-methylpyridin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; 4-(2-(1-(1-Acryloylpiperidin-4-yl)-1H-pyrazol-4-yl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-Amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(2,2-difluorocyclopropyl)-2-methoxybenzamide; 4-(6-(4-Acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(2-fluoroethyl)-2-methoxybenzamide; 4-(4-Amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(2-fluoroethyl)-2-methoxybenzamide; 4-(6-(4-Acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(2,2-difluoroethyl)-2-methoxybenzamide; 4-(4-Amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(2,2-difluoroethyl)-2-methoxybenzamide; 4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-(2,2-difluoroethyl)-2-methoxybenzamide; 4-(4-Amino-6-(2-chloro-4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-cyclopropyl-2-methoxybenzamide; 4-(2-(1-Acryloylpyrrolidin-3-yl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(6-(1-(1-Acryloylpiperidin-4-yl)-1H-pyrazol-4-yl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; N-(4-(4-Amino-7-oxo-3-(4-(pyrrolidin-1-ylmethyl)phenyl)-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; 4-Amino-3-(4-(cyclohexyloxy)phenyl)-2-(6-ethynylpyridin-3-yl)-2,6-dihydro-7H-pyrazolo[3,4-d]pyridazin-7-one; 4-(4-Amino-6-(4-(2-fluoroacrylamido)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-((1-fluorocyclopropyl)methyl)-2-methoxybenzamide; N-(4-(4-Amino-5-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(4-cyclobutoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-Amino-5-(4-cyclobutoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)methacrylamide; N-(4-(4-Amino-5-(4-cyclobutoxy-3-fluorophenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; 4-(6-(1-Acryloylpyrrolidin-3-yl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-((1-fluorocyclopropyl)methyl)-2-methoxybenzamide; 4-(2-(4-Acrylamido-3-fluorophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclopropyl-2-methoxybenzamide; 4-(2-(4-Acrylamido-3-fluorophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(2-(1-Acryloyl-2,5-dihydro-1H-pyrrol-3-yl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; N-(4-(4-Amino-3-bromo-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)-2-fluoroacrylamide; 1-(4-Acrylamidophenyl)-3-amino-5-(3-methoxy-4-((6-methylpyridin-2-yl)oxy)phenyl)-1H-pyrazole-4-carboxamide; N-(4-(4-Amino-7-oxo-3-(4-(pyrrolidin-1-yl)phenyl)-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-3-(3-methoxy-4-((6-methylpyridin-2-yl)oxy)phenyl)-2H-pyrazolo[3,4-d]pyrimidin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(6-cyclobutoxypyridin-3-yl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(4-cyclobutoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)-3-fluorophenyl)acrylamide; N-(4-(4-Amino-5-(4-cyclobutoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)-3-methoxyphenyl)acrylamide; N-(4-(4-Amino-5-(4-(cyclopropylmethoxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(4-cyclopropoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(4-(cyclohexylthio)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-3-bromo-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(4-(2,2,2-trifluoroethoxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(4-isopropoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(4-(oxetan-3-yloxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(4-(cyclohexyloxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(4-((tetrahydro-2H-pyran-4-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(4-((3-methylcyclohexyl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(4-((4,4-dimethylcyclohexyl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(6-(4-Acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxyphenyl)cyclopropanecarboxamide; N-(4-(4-Amino-5-(4-(1-(cyclopropylamino)-2,2,2-trifluoroethyl)-3-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; 4-(4-Amino-6-(2-fluoro-4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(3,3-difluorocyclobutyl)-2-methoxybenzamide; 4-(4-Amino-7-cyano-2-(4-(2-fluoroacrylamide)phenyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclopropyl-2-methoxybenzamide; 4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-(2-fluoroethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclopropyl-2-methoxybenzamide; N-(4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxyphenyl)cyclopropanecarboxamide; N-(4-(4-Amino-7-cyano-3-(4-((5-fluoropyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(4-((3,3-difluorocyclopentyl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(4-cyclobutoxy-3-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(4-(1-(cyclopropylamino)-2,2,2-trifluoroethyl)-3-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; 4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-ethyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclopropyl-2-methoxybenzamide; N-(4-(4-Amino-7-cyano-3-(4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(4-(1-(cyclopropylamino)-2,2,2-trifluoroethyl)-3-methoxyphenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(4-((4,4-difluorocyclohexyl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(4-((1-methylazetidin-3-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(4-(3-(dimethylamino)cyclobutoxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; 4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-Amino-6-(2-fluoro-4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(3-fluorocyclobutyl)-2-methoxybenzamide; 4-(4-Amino-6-(4-(2-fluoroacrylamide)-2-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-((1-fluorocyclopropyl)methyl)-2-methoxybenzamide; 4-(4-Amino-6-(4-(2-fluoroacrylamide)-2-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(2,2-difluoroethyl)-2-methoxybenzamide; 4-(4-Amino-6-(6-(2-fluoroacrylamide)pyridin-3-yl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-Amino-6-(3-fluoro-4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-Amino-6-(4-(2-fluoroacrylamide)-3-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-Amino-6-(4-(2-fluoroacrylamide)-2-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(3-fluorocyclobutyl)-2-methoxybenzamide; 4-(4-Amino-6-(2-fluoro-4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(1-methylcyclopropyl)benzamide; 4-(4-Amino-6-(4-(2-fluoroacrylamide)-2-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(1-methylcyclopropyl)benzamide; 4-(4-Amino-6-(2-fluoro-4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-((1-fluorocyclopropyl)methyl)-2-methoxybenzamide; 4-(4-Amino-6-(4-(2-fluoroacrylamide)-2-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(2,2-difluorocyclopropyl)-2-methoxybenzamide; N-(4-(4-Amino-5-(4-(bicyclo[3.1.0]hexan-3-yloxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(4-((3-fluorocyclopentyl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide N-(5-(4-Amino-5-(4-cyclobutoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)pyridin-2-yl)acrylamide; N-(4-(6-(4-Acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)phenyl)cyclopropanecarboxamide; N-(4-(4-Amino-5-(4-(pyrrolidin-1-yl)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxyphenyl)cyclobutanecarboxamide; N-(4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxyphenyl)cyclopentanecarboxamide; 4-(4-Amino-7-cyano-2-(2-fluoro-4-(2-fluoroacrylamido)phenyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclopropyl-2-methoxybenzamide; 4-(6-(4-Acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(1-cyanocyclopropyl)-2-methoxybenzamide; 4-(6-(4-Acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(bicyclo[1.1.1]pentan-1-yl)-2-methoxybenzamide; 4-(4-Amino-6-(4-(2-fluoroacrylamido)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(bicyclo[1.1.1]pentan-1-yl)-2-methoxybenzamide; 4-(4-Amino-6-(2-fluoro-4-(2-fluoroacrylamido)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(2,2-difluorocyclopropyl)-2-methoxybenzamide; N-(4-(6-(4-Acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxyphenyl)cyclobutanecarboxamide; N-(4-(4-Amino-5-(4-(3-methoxycyclobutoxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(4-(spiro[2.3]hexan-5-yloxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; 4-(2-(4-Acrylamido-2-methoxyphenyl)-4-amino-7-cyano-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-(3,3-difluorocyclobutyl)-2-methoxybenzamide; N-(4-(4-Amino-7-cyano-3-(3-methoxy-4-propionamidophenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; 4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-(2-fluoroethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-(3,3-difluorocyclobutyl)-2-methoxybenzamide; 4-(4-Amino-6-(4-(2-fluoroacrylamido)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(1-cyanocyclopropyl)-2-methoxybenzamide; N-(4-(4-Amino-5-(4-(cyclobutylamino)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; 4-(2-(4-Acrylamido-2-fluorophenyl)-4-amino-7-cyano-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-(3,3-difluorocyclobutyl)-2-methoxybenzamide; 4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-isopropyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-(3,3-difluorocyclobutyl)-2-methoxybenzamide; N-(4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxyphenyl)-N-methylcyclopropanecarboxamide; N-(4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)phenyl)cyclopropanecarboxamide; N-(4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxyphenyl)-3,3-difluorocyclobutane-1-carboxamide; N-(4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxyphenyl)-1-methylcyclopropane-1-carboxamide; N-(4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxyphenyl)-1-fluorocyclopropane-1-carboxamide; N-(4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxyphenyl)-1-(trifluoromethyl)cyclopropane-1-carboxamide; 4-(4-Amino-6-(2-fluoro-4-(2-fluoroacrylamido)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(2,2-difluoroethyl)-2-methoxybenzamide; N-(4-(4-Amino-7-cyano-3-(4-cyclobutoxy-3-methoxyphenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxyphenyl)-2,2-difluorocyclopropane-1-carboxamide; N-(4-(4-Amino-7-cyano-3-(4-(3-cyclopropylureido)-3-methoxyphenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; 4-(4-Amino-6-(4-(2-fluoroacrylamido)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(1,1,1-trifluoropropan-2-yl)benzamide; 4-(4-Amino-6-(3-((dimethylamino)methyl)-4-(2-fluoroacrylamido)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; N-(4-(4-Amino-5-(4-(azetidin-1-yl)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(4-(3-cyclopropylureido)-3-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(6-(4-Acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxyphenyl)azetidine-1-carboxamide; N-(4-(4-Amino-7-cyano-3-(4-(cyclobutylamino)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxyphenyl)azetidine-1-carboxamide; 4-(2-(4-Acrylamido-3-((dimethylamino)methyl)phenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)-2-fluoroacrylamide; 4-(4-Amino-7-cyano-2-(4-(2-fluoroacrylamido)phenyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-Amino-7-cyano-2-(4-(2-fluoroacrylamido)phenyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(1-(trifluoromethyl)cyclopropyl)benzamide; 4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-(2-methoxyethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-(3,3-difluorocyclobutyl)-2-methoxybenzamide; 4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-(2-fluoroethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(1-(trifluoromethyl)cyclopropyl)benzamide; 4-(6-(4-Acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(1-(trifluoromethyl)cyclopropyl)benzamide; 4-(4-Amino-6-(4-(2-fluoroacrylamido)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(1-(trifluoromethyl)cyclopropyl)benzamide; 4-(4-Amino-6-(4-(2-fluoroacrylamido)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-((1-(trifluoromethyl)cyclopropyl)methyl)benzamide; 4-(4-Amino-6-(4-(2-fluoroacrylamido)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(3,3,3-trifluoropropyl)benzamide; 4-(6-(4-Acrylamido-3-((dimethylamino)methyl)phenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(6-(4-Acrylamido-2-((dimethylamino)methyl)phenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; N-(4-(4-Amino-5-(3-methoxy-4-(pyrrolidin-1-yl)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(4-(cyclobutylamino)-3-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-(pyrrolidin-1-yl)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(3-methoxy-4-(pyrrolidin-1-yl)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(4-(cyclobutylamino)-3-methoxyphenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; 4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-(2-methoxyethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-Amino-7-cyano-2-(4-(2-fluoroacrylamide)phenyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-(3,3-difluorocyclobutyl)-2-methoxybenzamide; 4-(4-Amino-7-cyano-2-(4-(2-fluoroacrylamide)phenyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-(2,2-difluorocyclopropyl)-2-methoxybenzamide; 4-(4-Amino-7-cyano-2-(4-(2-fluoroacrylamide)phenyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(1-methylcyclopropyl)benzamide; N-(4-(4-Amino-5-(1-methyl-1H-indol-5-yl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(1-methyl-1H-indol-5-yl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; 4-(4-Amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(2,2,2-trifluoroethyl)benzamide; N-(4-(4-Amino-5-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(1-methyl-1H-indol-5-yl)-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-3-(benzo[b]thiophen-2-yl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; 4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-isopropyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-Amino-6-(4-(2-fluoroacrylamido)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(3-fluorobicyclo[1.1.1]pentan-1-yl)-2-methoxybenzamide; N-(4-(4-Amino-5-(benzo[b]thiophen-2-yl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-Amino-5-(benzo[b]thiophen-2-yl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; 4-(4-Amino-6-(4-(2-fluoroacrylamido)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-((3,3-difluorocyclobutyl)methyl)-2-methoxybenzamide; 4-(4-Amino-6-(4-(2-fluoroacrylamido)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-fluoro-N-(2,2,2-trifluoroethyl)benzamide; N-(4-(4-Amino-5-(3-fluoro-4-((5-fluoropyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; 4-(4-Amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(3-(trifluoromethyl)bicyclo[1.1.1]pentan-1-yl)benzamide; 4-(4-Amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(1,1-difluoropropan-2-yl)-2-methoxybenzamide; N-(4-(6-(4-Acrylamidephenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxyphenyl)-3,3-difluorocyclobutane-1-carboxamide; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-(bicyclo[1.1.1]pentan-1-yl)-2-methoxybenzamide; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclopropyl-2-methoxybenzamide; N-(4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-fluorophenyl)cyclopropanecarboxamide; 4-(3-Acrylamide-12-amino-9-cyano-6,7-dihydro-5H-benzo[c]pyrido[3',4':4,5]pyrrolo[1,2-a]azepin-13-yl)-N-(3,3-difluorocyclobutyl)-2-methoxybenzamide; 4-(4-Amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-(methylthio)-N-(2,2,2-trifluoroethyl)benzamide; N-(4-(4-Amino-5-(2-(4-methoxyphenyl)thiazol-5-yl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-Amino-5-(2-(4-methoxyphenyl)thiazol-5-yl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; 4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-cyclopropyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-(methylthio)-N-(2,2,2-trifluoroethyl)benzamide; N-(4-(4-Amino-5-(3-methoxy-4-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(3-methoxy-4-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; 4-(4-Amino-6-(2-fluoro-4-(2-fluoroacrylamido)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(1-(trifluoromethyl)cyclopropyl)benzamide; 4-(4-Amino-6-(2-fluoro-4-(2-fluoroacrylamido)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(bicyclo[1.1.1]pentan-1-yl)-2-methoxybenzamide; 4-(4-Amino-6-(2-fluoro-4-(2-fluoroacrylamido)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-((1-(trifluoromethyl)cyclopropyl)methyl)benzamide; 4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-cyclopropyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclopropyl-2-methoxybenzamide; N-(4-(4-Amino-5-(3-methoxy-4-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; 4-(4-Amino-6-(2-fluoro-4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(((1-(trifluoromethyl)cyclopropyl)methyl)benzamide); 4-(4-Amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(2,2-difluoropropyl)-2-methoxybenzamide; N-(4-(4-Amino-5-(4-(azetidine-1-carbonyl)-3-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-Amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-Amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(3-fluoro-4-((2-methylpyrimidin-4-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-Amino-5-(3-fluoro-4-((2-methylpyrimidin-4-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(1-oxo-2-(2,2,2-trifluoroethyl)-1,2-dihydroisoquinolin-6-yl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(1-oxo-2-(2,2,2-trifluoroethyl)isoindolin-5-yl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; 4-(4-Amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(((1-fluorocyclopropyl)methyl))-2-(methoxy-d3)benzamide; N-(4-(4-Amino-5-(3-fluoro-4-((6-methylpyrazin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-Amino-5-(3-fluoro-4-((6-methylpyrazin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(3-fluoro-4-((5-methylpyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-Amino-5-(3-fluoro-4-((5-methylpyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(3-fluoro-4-(pyrimidin-2-yloxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-Amino-3-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-2H-pyrazolo[3,4-d]pyrimidin-2-yl)phenyl)methacrylamide; N-(4-(4-Amino-5-(3-fluoro-4-((4-methoxypyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-Amino-5-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)-3-fluorophenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-Amino-5-(3-fluoro-4-((6-methylpyrimidin-4-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-Amino-5-(3-fluoro-4-((6-methylpyrimidin-4-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; 4-(4-Amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-((1-fluorocyclopropyl)methyl)benzamide; N-(4-(4-Amino-5-(3-fluoro-4-((4-methylpyrimidin-2-yl)thio)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-Amino-5-(3-fluoro-4-((4-methylpyrimidin-2-yl)thio)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-Amino-5-(4-((4-cyclopropylpyrimidin-2-yl)oxy)-3-fluorophenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide N-(4-(4-Amino-5-(4-((4-cyclopropylpyrimidin-2-yl)oxy)-3-fluorophenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(3-fluoro-4-(imidazo[1,2-c]pyrimidin-5-yloxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-Amino-5-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)-3-fluorophenyl)methacrylamide; 4-(4-Amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-phenylbenzamide; 4-(4-Amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(pyridin-2-yl)benzamide; N-(4-(4-Amino-5-(3-fluoro-4-(methyl(4-methylpyrimidin-2-yl)amino)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-Amino-5-(3-fluoro-4-((4-(trifluoromethyl)pyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-Amino-5-(3-fluoro-4-((4-(trifluoromethyl)pyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; 4-(4-Amino-6-(4-(but-2-inamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(1-(trifluoromethyl)cyclopropyl)benzamide; 4-(4-Amino-6-(4-prop-2-ynamidephenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(1-(trifluoromethyl)cyclopropyl)benzamide; 4-(4-Amino-6-(4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(tert-butyl)-2-methoxybenzamide; N-(4-(4-Amino-5-(4-((4-ethylpyrimidin-2-yl)oxy)-3-fluorophenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-Amino-5-(4-((4-ethylpyrimidin-2-yl)oxy)-3-fluorophenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(3-fluoro-4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-Amino-5-(3-fluoro-4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(3-fluoro-4-((4-methylpyrimidin-2-yl)amino)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-Amino-5-(3-fluoro-4-((4-methylpyrimidin-2-yl)amino)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(3-fluoro-4-((4-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-Amino-5-(3-fluoro-4-((4-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(4-(4-fluorobenzoyl)-3-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)methacrylamide; N-(4-(4-Amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)but-2-ynamide; N-(4-(4-Amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)prop-2-ynamide; N-(4-(4-Amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)ethenesulfonamide; (E)-N-(4-(4-Amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-4-(dimethylamino)but-2-enamide; 1-(4-(4-Amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)-3,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one; (E)-N-(4-(4-Amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)but-2-enamide 4-(4-Amino-6-(4-(2-fluoroacrylamido)-2-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(1-(trifluoromethyl)cyclopropyl)benzamide; 4-(4-Amino-6-(4-(2-fluoroacrylamido)-2-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(3-fluorobicyclo[1.1.1]pentan-1-yl)-2-methoxybenzamide; N-(4-(4-Amino-5-(3-fluoro-4-(methyl(4-methylpyrimidin-2-yl)amino)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(4-benzoyl-3-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(4-(4,4-difluorocyclohexane-1-carbonyl)-3-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; 1-(4-(4-Amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)piperidin-1-yl)prop-2-en-1-one; 1-(4-(4-(4-Amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)-1H-pyrazol-1-yl)piperidin-1-yl)prop-2-en-1-one; N-(4-(4-Amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-((dimethylamino)methyl)acrylamide; N-(4-(4-Amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-chloroacetamide; N-(4-(4-Amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-chloroacrylamide; (Z)-4-((4-(4-Amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)amino)-4-oxobut-2-enoic acid; 4-(4-Amino-6-(4-(2-fluoroacrylamide)-2-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(bicyclo[1.1.1]pentan-1-yl)-2-methoxybenzamide; 4-(4-Amino-6-(2-fluoro-4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(3-fluorobicyclo[1.1.1]pentan-1-yl)-2-methoxybenzamide; N-(4-(4-Amino-5-(4-((4-aminopyrimidin-2-yl)oxy)-3-fluorophenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; 4-(4-Amino-6-(2-fluoro-4-methacrylamidephenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(1-(trifluoromethyl)cyclopropyl)benzamide; N-(4-(4-Amino-7-cyano-3-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(4-(cyclohexanecarbonyl)-3-methoxyphenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; 4-(4-Amino-6-(4-(2-fluoroacrylamide)-2-(trifluoromethyl)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(1-(trifluoromethyl)cyclopropyl)benzamide; N-(4-(4-Amino-5-(3-fluoro-4-((4-(methylamino)pyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)-3-fluorophenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(3-fluoro-4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-((6-methylpyridin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)-3-fluorophenyl)-2-fluoroacrylamide; N-(4-(4-Amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)-3-methylphenyl)-2-fluoroacrylamide; N-(4-(4-Amino-7-cyano-3-(3-fluoro-4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(2-(1-methylcyclopropyl)benzo[d]thiazol-6-yl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(3-methoxy-4-((1-methylcyclohexyl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(3-fluoro-4-(pyrimidin-2-yloxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(4-(((4-(difluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; 4-(4-Amino-6-(2-chloro-4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(1-(trifluoromethyl)cyclopropyl)benzamide; 4-(4-Amino-6-(4-(2-fluoroacrylamide)-2-methylphenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(1-(trifluoromethyl)cyclopropyl)benzamide; 4-(4-Amino-6-(2-chloro-4-(2-fluoroacrylamide)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(1-(trifluoromethyl)cyclopropyl)benzamide; N-(4-(4-Amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)-3-chlorophenyl)-2-fluoroacrylamide; N-(4-(4-Amino-5-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)-3-methoxyphenyl)methacrylamide; N-(4-(4-Amino-5-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)-3-methylphenyl)methacrylamide; N-(4-(4-Amino-5-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-Amino-5-(3-fluoro-4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)methacrylamide; N-(4-(4-Amino-5-(3-fluoro-4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-Amino-5-(3-fluoro-4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)but-2-ynamide; N-(4-(4-Amino-5-(3-fluoro-4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)prop-2-ynamide; N-(4-(4-Amino-5-(3-methoxy-4-(1-methyl-1H-imidazole-2-carbonyl)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(4-((5-fluoropyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-Amino-5-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)-3-methoxyphenyl)-2-fluoroacrylamide; N-(4-(4-Amino-7-cyano-3-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)-3-fluorophenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(3-fluoro-4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(3-fluoro-4-(pyrimidin-2-yloxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(4-((4-ethylpyrimidin-2-yl)oxy)-3-fluorophenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(3-fluoro-4-(pyridin-2-yloxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-((6-methylpyridin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-(pyrimidin-2-yloxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; 4-(4-Amino-7-cyano-2-(2-fluoro-4-methacrylamidephenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; N-(4-(4-Amino-3-(3-chloro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(3-methyl-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(3,5-difluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(4-((4,5-dimethylpyrimidin-2-yl)oxy)-3-fluorophenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(3-fluoro-4-((5-fluoropyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(3-fluoro-4-(pyridin-2-yloxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(3-fluoro-4-((5-fluoropyridin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(4-((4,5-dimethylpyrimidin-2-yl)oxy)-3-fluorophenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(4-(cyclohexyloxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; 4-(4-Amino-7-cyano-2-(2-fluoro-4-methacrylamidephenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(1-(trifluoromethyl)cyclopropyl)benzamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-(pyridin-2-yloxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-(pyridin-2-yloxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(3-fluoro-4-((5-fluoropyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-Amino-3-(3-chloro-4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-3-(4-((6-chloropyridin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(2,5-difluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(2,3-difluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-2-fluoro-3-methylphenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(2-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(3-fluoro-4-((5-fluoropyridin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(4-((5-fluoropyridin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)-3-methylphenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(3,5-difluoro-4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)acrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(4-((5-fluoropyridin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(2,3-difluoro-4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(4-(cyclohexyloxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(4-(cyclohexanecarbonyl)-3-fluorophenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(3-fluoro-4-(thiazol-2-yloxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(3-fluoro-4-((4-methylthiazol-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(3-fluoro-4-((4-(trifluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(3-fluoro-4-((4-(trifluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-2,3-difluorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(3-fluoro-4-((5-fluoro-6-methylpyridin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(3-fluoro-4-((5-fluoro-6-methylpyridin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-2,3-difluorophenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(4-(cyclohexyloxy)-3-fluorophenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(4-((1,5-dimethyl-1H-pyrazol-3-yl)oxy)-3-fluorophenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(3-fluoro-4-((1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-(((1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-(((4-(trifluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-(((4-(trifluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(4-(((4,6-dimethylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(4-(((4-(difluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(4-(((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-(((1-methyl-1H-pyrazol-5-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(3-methyl-4-(((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(4-(((1-cyclopropyl-1H-pyrazol-3-yl)oxy)-3-fluorophenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-3-(3-chloro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-((6-methylpyridin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; 4-(3-Acrylamido-12-amino-9-cyano-6,7-dihydrobenzo[f]pyrido[3',4':4,5]pyrrolo[1,2-d][1,4]oxazepin-13-yl)-N-(3,3-difluorocyclobutyl)-2-methoxybenzamide; N-(4-(4-Amino-3-(3-chloro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)acrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(4-(cyclohexyloxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-Amino-5-(4-(cyclohexyloxy)-3-fluorophenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-Amino-5-(4-(cyclohexyloxy)-3-fluorophenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(4-(cyclohexyloxy)-3-fluorophenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-5-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)acrylamide; 4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-Amino-6-(4-(2-fluoroacrylamido)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-Amino-7-cyano-2-(4-(2-fluoroacrylamido)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-Amino-6-(2-fluoro-4-(2-fluoroacrylamido)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(4-Amino-6-(4-(2-fluoroacrylamido)phenyl)pyrazolo[5,1-f][1,2,4]triazin-5-yl)-N-(3,3-difluorocyclobutyl)benzamide; N-(4-(6-(4-Acrylamidophenyl)-4-aminopyrazolo[5,1-f][1,2,4]triazin-5-yl)-2-methoxyphenyl)-2,2-difluorocyclopropane-1-carboxamide; N-(4-(4-Amino-7-cyano-3-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-Amino-5-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)pyrazolo[5,1-f][1,2,4]triazin-6-yl)phenyl)methacrylamide; 4-(2-(4-Acrylamidophenyl)-4-amino-7-cyano-1-(methyl-d3)-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; N-(4-(4-Amino-7-cyano-3-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(3-fluoro-4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-Amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; 4-(3-Acrylamido-12-amino-9-cyano-6,7-dihydrobenzo[f]pyrido[3',4':4,5]pyrrolo[1,2-d][1,4]oxazepin-13-yl)-N-(3,3-difluorocyclobutyl)-2-methoxybenzamide; N-(4-(4-Amino-7-cyano-3-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(3-methyl-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-((6-methylpyridin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)-3-fluorophenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(3-fluoro-4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(3-fluoro-4-((4-(trifluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)-2-fluoroacrylamide; N-(4-(4-Amino-7-cyano-3-(4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)-2-fluoroacrylamide; N-(4-(4-Amino-7-cyano-3-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)-2-fluoroacrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)-2-fluoroacrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-((6-methylpyridin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)-2-fluoroacrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)-2-fluoroacrylamide; N-(4-(4-Amino-7-cyano-3-(4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)-2-fluoroacrylamide; N-(4-(4-Amino-7-cyano-3-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)-2-fluoroacrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)-2-fluoroacrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-((6-methylpyridin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)-2-fluoroacrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)-2-fluoroacrylamide; N-(4-(4-Amino-7-cyano-3-(4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)-2-fluoroacrylamide; N-(4-(4-Amino-7-cyano-3-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)-2-fluoroacrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)-2-fluoroacrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-(((6-methylpyridin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)-2-fluoroacrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-(((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(4-(((4-(difluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)acrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-(((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)acrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-(((6-methylpyridin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)acrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-(((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(4-(((4-(difluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)acrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-(((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)acrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-(((6-methylpyridin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)acrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)acrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-((6-methylpyridin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)-2-methylprop-2-enethioamide; N-(4-(4-Amino-7-cyano-3-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-1-ethyl-3-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-1-(2-fluoroethyl)-3-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(4-((4-(difluoromethyl)-5-fluoropyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(4-((4-(difluoromethyl)-5-fluoropyrimidin-2-yl)oxy)-3-fluorophenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-3-(3-chloro-5-fluoro-4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(3-fluoro-4-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-7-cyano-3-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3,5-difluorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluoro-5-methylphenyl)methacrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-(trifluoromethyl)phenyl)methacrylamide; N-(4-(4-Amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)-3,5-difluorophenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-3-(4-((5-chloro-4-(trifluoromethyl)pyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-3-(4-((5-chloro-4-(trifluoromethyl)pyrimidin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-((4-(trifluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-Amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide; N-(4-(4-Amino-7-cyano-1-methyl-3-(4-((4-(trifluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide; N-(4-(4-Amino-7-cyano-3-(3-fluoro-4-((4-(trifluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide; N-(4-(4-Amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)but-2-ynamide; N-(4-(4-Amino-3-(4-((5-chloro-4-(difluoromethyl)pyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-3-(4-((5-chloro-4-(difluoromethyl)pyrimidin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-Amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)-2-fluoroacrylamide; N-(4-(4-Amino-3-(4-((5-chloro-6-methylpyridin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-3-(4-((5-chloro-6-methylpyridin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-3-(3-chloro-4-((5-chloro-4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)-3-methylphenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-Amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; N-(4-(4-Amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)acrylamide; N-(4-(4-Amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)acrylamide; N-(4-(4-Amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)-2-fluoroacrylamide; N-(4-(4-Amino-3-(4-(((5-chloro-4-methylpyrimidin-2-yl)oxy)phenyl))-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)-2-fluoroacrylamide; N-(4-(4-Amino-3-(4-(((5-chloro-4-methylpyrimidin-2-yl)oxy)-3-fluorophenyl))-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)acrylamide; N-(4-(4-Amino-3-(4-(((5-chloro-4-methylpyrimidin-2-yl)oxy)phenyl))-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)acrylamide; N-(4-(4-Amino-3-(4-(((5-chloro-4-methylpyrimidin-2-yl)oxy)-3-fluorophenyl))-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)-2-fluoroacrylamide; N-(4-(4-Amino-3-(4-(((5-chloro-4-methylpyrimidin-2-yl)oxy)phenyl))-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)-2-fluoroacrylamide; N-(4-(4-Amino-3-(4-(((5-chloro-4-methylpyrimidin-2-yl)oxy)-3-fluorophenyl))-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)acrylamide; N-(4-(4-Amino-3-(4-(((5-chloro-4-methylpyrimidin-2-yl)oxy)phenyl))-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)acrylamide; N-(4-(4-Amino-3-(4-(((5-chloro-4-methylpyrimidin-2-yl)oxy)-3-fluorophenyl))-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)-2-fluoroacrylamide; or N-(4-(4-Amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)-2-fluoroacrylamide A compound independently selected from

26. A compound which is N-(4-(4-Amino-7-cyano-1-methyl-3-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide.

27. A pharmaceutical composition comprising a therapeutically effective amount of the compound according to any one of claims 1 to 26 and a pharmaceutically acceptable carrier for inhibiting FGFR2 signaling activity in a subject.

28. A pharmaceutical composition for inhibiting FGFR2 signaling activity in a subject, which comprises administering a therapeutically effective amount of the compound according to claim 25 or 26 and a pharmaceutically acceptable carrier.

29. A pharmaceutical composition for treating an FGFR2-mediated disorder in a subject, which comprises administering a therapeutically effective amount of the compound according to any one of claims 1 to 26 and a pharmaceutically acceptable carrier.

30. A pharmaceutical composition for treating an FGFR2-mediated disorder in a subject, which comprises administering a therapeutically effective amount of the compound according to claim 25 or 26 and a pharmaceutically acceptable carrier.

31. A pharmaceutical composition comprising administering a therapeutically effective amount of the compound according to any one of claims 1 to 26 to a subject in need thereof for treating a disorder in the subject, wherein the disorder is cholangiocarcinoma, liver cancer, breast cancer, prostate cancer, lung cancer, thyroid cancer, gastric cancer, ovarian cancer, rectal cancer, endometrial cancer, or urothelial cancer.

32. A pharmaceutical composition for treating a disorder in a subject, which comprises administering a therapeutically effective amount of the compound according to claim 25 or 26 to a subject in need thereof, wherein the disorder is cholangiocarcinoma, liver cancer, breast cancer, prostate cancer, lung cancer, thyroid cancer, gastric cancer, ovarian cancer, rectal cancer, endometrial cancer, or urothelial cancer.

33. The pharmaceutical composition according to claim 31, wherein the disorder is cholangiocarcinoma.

34. The pharmaceutical composition according to claim 33, wherein the cholangiocarcinoma is intrahepatic cholangiocarcinoma.

35. The pharmaceutical composition according to claim 31, wherein the disorder is liver cancer.

36. The pharmaceutical composition according to claim 35, wherein the liver cancer is hepatocellular carcinoma.

37. The pharmaceutical composition according to claim 31, wherein the disorder is lung cancer.

38. The pharmaceutical composition according to claim 37, wherein the lung cancer is squamous cell lung cancer or non-small cell lung cancer.

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