TW202400159A - Fgfr inhibitors and methods of use thereof - Google Patents

Abstract

Provide novel compounds of Formula (I) and pharmaceutical composition, pharmaceutically acceptable salt, prodrug, solvate, hydrate, tautomer, and isomer thereof, useful as FGFR inhibitors to modulate or inhibit the activity of FGFR enzymes. Further relates to, but is not limited to, methods for treating disorders associated with FGFR signaling with the compounds and compositions.

Description

FGFR inhibitors and methods of use

The present invention relates to certain novel fused heterocyclic derivative compounds represented by formula (I) and/or (II) as FGFR inhibitors, salts thereof and pharmaceutical compositions thereof. The present invention describes methods for treating FGFR-mediated diseases and cancers and inhibiting FGFR activity, as well as methods for treating FGFR-related diseases and cancers, and also describes methods for preparing compounds represented by formula (I) and/or (II). . In particular, the present invention relates to fused heterocyclic derivatives that are useful as FGFR inhibitors, as well as methods of preparing such compounds and methods of treating FGFR-mediated diseases.

Fibroblast growth factor receptors (FGFR1, FGFR2, FGFR3, and FGFR4) are receptor tyrosine kinases composed of an extracellular ligand-binding domain and an intracellular tyrosine kinase domain. Binding of FGF ligands results in receptor dimerization and conformational changes in the intracellular domain, resulting in intermolecular transphosphorylation of the kinase domain and intracellular tail. Phosphorylated residues serve as docking sites for adapter proteins and promote downstream signaling pathways, leading to a series of cell behaviors including proliferation, survival, differentiation, migration, and angiogenesis. FGFR gene amplification or fusion, FGFR missense mutations, receptor overexpression due to dysregulation of epigenetic and/or transcriptional regulatory factors, or upregulation of FGF ligands in the tumor microenvironment may lead to dysregulation of the FGFR signaling pathway. FGFR is expressed on a variety of cell types, so abnormal FGFR signal transduction is related to tumorigenesis, tumor progression, and treatment resistance of various tumors. (For a review of FGFR signaling, see N. Turner and R. Grose, Nat. Rev. Cancer 2010, 10:116-129; and references cited therein.)

Pan-inhibitors of FGFR1-3 have produced clinical responses in many cancers with FGFR abnormalities, but on-target toxicity limits the dosage of these inhibitors. One of the most common adverse reactions of pan-FGFR inhibitors is hyperphosphatemia. FGFR1 mediates the regulation of phosphate reabsorption, therefore, an FGFR-selective inhibitor that can exclude FGFR1 is needed (J. Gattineni et al., Am. J Physiol. Renal Physiol 2014, 306: F351-F358; X. Han et al., PLoS One 2016, l l:e0147845). Cancers harboring FGFR2 gene fusions, FGFR2 amplifications, and/or FGFR2 activating mutations all respond to FGFR pan-inhibitors, but lower response rates and shorter response durations suggest they are limited by drug toxicity. Therefore, there is an urgent need for compounds that act as selective inhibitors of FGFR2, as well as methods of using these compounds to treat cancer and other diseases.

The present invention provides compounds represented by general formula (I) and/or general formula (II) that can be used as FGFR2 inhibitors, including pharmaceutical compositions, pharmaceutically acceptable salts, prodrugs, solvates, and hydrates thereof, Tautomers and isomers.

The compound represented by formula (I) provided by the invention:

Formula (I)

or its pharmaceutically acceptable salts, prodrugs, solvates, hydrates, tautomers and isomers,

R ₁ is selected from H, CN or CONH ₂ ;

R ₂₁ is selected from H, D, CN, C _1-3 alkyl, C _1-3 alkoxy, C _3-6 cycloalkyl, -(CH ₂ ) _0-2 -NHC _1-3 alkyl, - (CH ₂ ) _0-2 N(C _1-3 alkyl) ₂ or 3- to 6-membered saturated heterocyclic ring with 1 or 2 heteroatoms selected from N, O or S; and each independently optionally Unsubstituted or each independently optionally substituted by 1, 2 or 3 groups selected from D, OH, halogen, C _1-3 alkyl, C _1-3 alkoxy or C _3-6 cycloalkyl;

Ring B is phenylene, a divalent 5- or 6-membered saturated or partially unsaturated heterocycle with 1 or 2 heteroatoms independently selected from N, O or S, or 5- or 6- Yuan has 1 or 2 heteroaromatic rings independently selected from N, O or S heteroatoms;

Ring D is phenylene, a divalent 5- or 6-membered saturated or partially unsaturated heterocyclic ring with 1 or 2 independently selected from N, O or S heteroatoms, a divalent 9- or 10-membered saturated or partially unsaturated fused heterocycle with 1 or 2 heteroatoms independently selected from N, O or S, 5- or 6-membered 1 or 2 heteroatoms independently selected from N , a heteroarylene ring of O or S heteroatoms, or a 9- or 10-membered fused heteroaromatic ring with 1 or 2 independently selected from N, O or S heteroatoms;

Each R ₂₂ is independently optionally selected from H, D, halogen, CN, NH ₂ , OH, C _1-3 alkyl, C _1-3 alkoxy, C _3-6 cycloalkyl, -(CH ₂ ) _0-2 -NHC _1-3 alkyl or -(CH ₂ ) _0-2 N(C _1-3 alkyl) ₂ , and each independently optionally unsubstituted or each independently optionally substituted by 1, 2 or 3 R _z substitutions;

Each R ₂₅ is independently optionally H, D, halogen, CN, OH, R ^′′ , N(R′′) ₂ , OR′′, or -SR′′;

_{Each _} -NH-, _-CH2- , -CONH-, -NHCO-, _-CONHCH2- , -NHCONH-, _-NHCOCH2- , or _-NHCOCH2CH2- , and each _CH2 independently is optionally _{unsubstituted} or Independently optionally substituted by 1, 2 or 3 groups selected from D, halogen, C _1-3 alkyl or C _1-3 haloalkyl, and each NH is independently optionally unsubstituted or independently optionally Substituted by 1, 2 or 3 C _1-3 alkyl groups;

It is a divalent bond or a trivalent bond;

1) When When it is a trivalent bond, each R ₂₃ is absent, and each R ₂₄ is independently selected from H, D, -C _0-3 alkylene-N(R′′) ₂ , -C _0-3 Alkylene-OR'' or R''; and each independently optionally unsubstituted or each independently optionally substituted by 1, 2 or 3 groups selected from D or halogen;

2) When When it is a divalent bond, each R ₂₃ or each R ₂₄ is independently selected from H, D, halogen, -C _0-3 alkylene -N(R′′) ₂ , -C _0-3 sub Alkyl-OR'' or R''; and each independently optionally unsubstituted or each independently optionally substituted with 1, 2 or 3 groups selected from D or halogen;

Each W is independently selected from C _1-3 alkyl, phenyl, 4- to 6-membered saturated or partially saturated heteroatom with 1 or 2 independently selected from N, O or S heteroatoms. Cyclic group, a 5- or 6-membered heteroaryl group having 1 to 3 heteroatoms independently selected from N, O or S, or a 3- to 6-membered saturated or partially saturated carbocyclic ring, and each Independently optionally unsubstituted or substituted by 1, 2 or 3 R _w ;

Each R _w 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 independently optionally unsubstituted or each independently optionally substituted by 1, 2 or 3 Rz;

Each y is independently and arbitrarily selected from 0, 1, 2, 3, or 4;

Each R _z is independently and arbitrarily selected from H, D, halogen, CN, -N(R′′) ₂ , -OR′′ or R′′;

Each R'' is independently optionally C _1-3 ^‏alkyl or C _3-6 cycloalkyl, and each R'' is independently optionally unsubstituted or each independently optionally substituted by 1, 2 or 3 selected from halogen or D group substitution.

In some specific embodiments, in the formula (I) provided by the present invention, ring B is a phenylene group, and the divalent 5- or 6-membered group has 1 or 2 saturated or partially selected N heteroatoms. Unsaturated heterocyclyl, or 5- or 6-membered heteroarylene group with 1 or 2 independently selected N heteroatoms.

In some specific embodiments, in formula (I) provided by the invention, ring B is , , , or .

In some specific embodiments, in the formula (I) provided by the present invention, ring D is a phenylene group, and the divalent 9- or 10-membered group has 1 or 2 independently selected from N, O or S heteroatoms. Saturated or partially unsaturated fused heterocyclic group, or 9- or 10-membered fused heteroarylene group with 1 or 2 independently selected from N, O or S heteroatoms.

In some specific embodiments, in formula (I) provided by the invention, Ring D is , or .

In some specific embodiments, in formula (I) provided by the present invention, R ₁ is CN.

In some specific embodiments, in the formula (I) provided by the invention, the compound is a compound represented by the following formula (II): Formula (II).

In some specific embodiments, in the formula (I) and/or formula (II) provided by the present invention, the R ₂₁ is selected from H, D, CN, NH ₂ , OH, methyl, ethyl, propyl, Isopropyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, -(CH ₂ ) _0-2 -NHCH ₃ , -(CH ₂ ) _0-2 -NHCH ₂ CH ₃ , -(CH ₂ ) _0-2 N(CH ₃ ) ₂ , -(CH ₂ ) _0-2 N(CH ₂ CH ₃ ) ₂ , -(CH ₂ ) _0-2 N(CH ₃ )(CH ₂ CH ₃ ), a 4-membered saturated heterocycle, a 5-membered saturated heterocycle or a 6-membered saturated heterocycle with 1 or 2 selected from N or O heteroatoms; and each independently any are unsubstituted or each is independently selected from 1, 2 or 3 D, OH, F, Cl, Br, methoxy, ethoxy or propoxy; the R ₂₂ is independently selected from From H, D, F, Cl, Br, CN, NH ₂ , OH, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, cyclopentyl , cyclohexyl, -(CH ₂ ) _0-2 -NHCH ₃ , -(CH ₂ ) _0-2 -NHCH ₂ CH ₃ , -(CH ₂ ) _0-2 N(CH ₃ ) ₂ , -(CH ₂ ) _0-2 N(CH ₂ CH ₃ ) ₂ or -(CH ₂ ) _0-2 N(CH ₃ CH ₂ CH ₃ ), each independently optionally unsubstituted or each independently optionally substituted with 1, 2, or 3 R _z is replaced.

In some specific embodiments, in the formula (I) and/or formula (II) provided by the present invention, the R ₂₁ is selected from H, D, CN, NH ₂ , OH, methyl, ethyl, methoxy , cyclopropyl, cyclohexyl, 4-membered saturated heterocyclic ring or 5-membered saturated heterocyclic ring with 1 or 2 selected from N or O heteroatoms; and each independently is optionally unsubstituted or each independently is optional is substituted with 1, 2 or 3 groups selected from D, OH, F or Cl; each R ₂₂ is selected from H, D, F, Cl, CN, NH ₂ , OH, methyl, ethyl, methane Oxy group, ethoxy group, cyclopropyl group, cyclobutyl group, -NHCH ₃ , -CH ₂ NHCH ₃ , -CH ₂ CH ₂ NHCH ₃ , -CH ₂ NHCH ₂ CH ₃ , -N(CH ₃ ) ₂ , - CH ₂ N(CH ₃ ) ₂ , -(CH ₂ ) ₂ N(CH ₃ ) ₂ , -N(CH ₃ CH ₂ CH ₃ ), -CH ₂ N(CH ₃ CH ₂ CH ₃ ) or -(CH ₂ ) ₂ N(CH ₃ CH ₂ CH ₃ ); and are each independently optionally unsubstituted or each independently optionally substituted by 1, 2 or 3 R _z .

In some specific embodiments, in the formula (I) and/or formula (II) provided by the present invention, the R ₂₁ is selected from , , , , , , , , , , , , , ,or ; The R ₂₂ is selected from , , , , , , , , , , , , , , or .

In some specific embodiments, in the formula (I) and/or formula (II) provided by the present invention, the R ₂₁ is selected from , , , , , , , or ; The R ₂₂ is selected from , , , , , , , , or .

In some specific embodiments, in the formula (I) and/or formula (II) provided by the present invention, each R ₂₅ is independently and optionally H, D, F, Cl, Br, CN, NH ₂ , OH, methyl, ethyl, propyl, isopropyl, -S-methyl, -S-ethyl, -S-propyl, methoxy, ethoxy or propoxy; and each independently any are unsubstituted or are each independently optionally substituted by 1, 2 or 3 groups selected from D, F, Cl or Br.

In some specific embodiments, in the formula (I) and/or formula (II) provided by the present invention, each R ₂₅ is independently and optionally H, D, F, Cl, methyl, ethyl, - S-methyl, -S-ethyl, methoxy or ethoxy; and each independently optionally unsubstituted or each independently optionally substituted with 1, 2 or 3 groups selected from D or F.

In some specific embodiments, in the formula (I) and/or formula (II) provided by the present invention, each R ₂₅ is independently and optionally H, D, F, Cl, methyl, ethyl, - S-methyl, methoxy or ethoxy; and each independently optionally unsubstituted or each independently optionally substituted with 1, 2 or 3 F.

In some specific embodiments, in the formula (I) and/or formula (II) provided by the present invention, each X or each L is independently and arbitrarily selected from covalent bonds, -O-, -CO- , -NH-, -CH ₂ -, -CONH- or -NHCO-.

In some specific embodiments, in the formula (I) and/or formula (II) provided by the present invention, each of the X's is independently and arbitrarily selected from -NH-; each of the L's is independently and arbitrarily selected. Selected from -O-, -NH-, -CONH- or -NHCO-.

In some specific embodiments, in formula (I) and/or formula (II) provided by the present invention, the is a divalent bond, and each R ₂₃ or each R ₂₄ is independently selected from H, D, F, Cl, Br, -N(R′′) ₂ , -CH ₂ N(R′′ ) ₂ , -(CH ₂ ) ₂ N(R′′) _{2 ,} -(CH ₂ ) ₃ N(R′′) ₂ or R′′; and each independently is optionally unsubstituted or each independently optionally is 1, 2 or 3 groups selected from D, F, Cl or Br are substituted.

In some specific embodiments, in formula (I) and/or formula (II) provided by the present invention, the is a divalent bond, and each R ₂₃ or each R ₂₄ is independently selected from H, D, F, Cl, methyl, ethyl, propyl, isopropyl or cyclopropyl; and each is independently selected Optionally unsubstituted or each independently optionally substituted by 1, 2 or 3 groups selected from D, F or Cl.

In some specific embodiments, in formula (I) and/or formula (II) provided by the present invention, the is a divalent bond, and each R ₂₃ or each R ₂₄ is independently optionally selected from H, D, F or methyl; and the methyl group is independently optionally unsubstituted or independently optionally substituted 1, 2 or 3 groups selected from D or F are substituted.

In some specific embodiments, in formula (I) and/or formula (II) provided by the present invention, the It is a trivalent bond, each R ₂₃ does not exist, and each R ₂₄ is independently selected from H, D, methyl, ethyl, propyl, isopropyl or cyclopropyl; And each independently is optionally unsubstituted or each independently is optionally substituted with 1, 2 or 3 groups selected from D, F or Cl.

In some specific embodiments, in formula (I) and/or formula (II) provided by the present invention, the is a trivalent bond, each R ₂₃ does not exist, and each R ₂₄ is independently selected from H, D or methyl; and the methyl is independently unsubstituted or independently is optionally substituted by 1, 2 or 3 groups selected from D or F.

In some specific embodiments, in the formula (I) and/or formula (II) provided by the present invention, the W is independently selected from methyl, phenyl, 4-, 5- or 6-membered. Or 2 saturated heterocycles selected from N, O or S heteroatoms, 5- or 6-membered heteroaryls with 1 or 2 heteroatoms selected from N or S, or 3-, 4-, 5- or 6-membered saturated carbocyclic ring.

In some specific embodiments, in formula (I) and/or formula (II) provided by the present invention, said W is independently and arbitrarily selected from a 5- or 6-membered saturated heterocycle with 1 N atom, 5 6-membered heteroaryls with 1 N atom and 1 S atom, 6-membered heteroaromatics with 1 or 2 N atoms, 3-membered saturated carbocyclic rings, 4-membered saturated carbocyclic rings, 5-membered saturated carbocyclic ring or 6-membered saturated carbocyclic ring.

In some specific embodiments, in formula (I) and/or formula (II) provided by the present invention, each R _w is independently selected from the group consisting of D, F, Cl, Br, OH, methoxy, CN, NH ₂ , methyl, ethyl, propyl, isopropyl, F or Cl substituted methyl, F or Cl substituted ethyl, F or Cl substituted propyl, F or Cl substituted isopropyl , cyclopropyl, cyclobutyl, cyclopentyl, vinyl or ethynyl; and each independently optionally unsubstituted or each independently optionally substituted by 1, 2 or 3 R _z .

In some specific embodiments, in the formula (I) and/or formula (II) provided by the present invention, each Rw is independently selected from D, F, Cl, methyl, 1, 2 or 3 Selected from methyl, methoxy or cyclopropyl substituted by F or D groups.

In some specific embodiments, in the formula (I) and/or formula (II) provided by the present invention, each R _z is independently and arbitrarily selected from D, F, Cl, Br, CN, -N(R ′′) ₂ , -OR′ or R′′.

In some specific embodiments, in formula (I) and/or formula (II) provided by the present invention, each R _z is independently and arbitrarily selected from D, F, Cl, Br, CN, -NH ₂ , Methyl, ethyl, propyl or isopropyl.

In some specific embodiments, in the formula (I) and/or formula (II) provided by the present invention, each Rz is independently selected from D, F, Cl or methyl.

In some specific embodiments, in formula (I) and/or formula (II) provided by the invention, each R′′ is independently and optionally methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl or cyclopentyl; and each independently optionally unsubstituted or each independently optionally substituted by 1, 2 or 3 groups selected from F, Cl or D.

In some specific embodiments, in formula (I) and/or formula (II) provided by the present invention, each R′′ is independently and arbitrarily selected from methyl, ethyl or propyl; and each R′′ is independently and arbitrarily selected from methyl, ethyl or propyl; Substituted or each independently optionally substituted by 1, 2 or 3 groups selected from D or F.

In some specific embodiments, among the compounds represented by formula (I) and/or formula (II) provided by the present invention, the compound is independently selected from: 4-(2-(4-Acrylamidephenyl)-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-(4-(2-fluoroacrylamide)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridine-3- base)-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- Pyrro[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- Pyrro[3,2-c]pyridin-2-yl)phenyl]-2-fluoroacrylamide; 4-(2-(4-Acrylamidephenyl)-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 Base-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- Pyrro[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 Base-1H-pyrrolo[3,2-c]pyridin-2-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-7-cyano-3-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl- 1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; 2-(4-Acrylamidephenyl)-4-amino-3-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl Base-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-Acrylamidephenyl)-4-amino-7-cyano-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclopropyl-2 -Methoxybenzamide; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-(2-hydroxyethyl)-1H-pyrrolo[3,2-c]pyridine-3- base)-N-cyclobutyl-2-methoxybenzamide; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-(2-methoxyethyl)-1H-pyrrolo[3,2-c]pyridine- 3-yl)-N-cyclobutyl-2-methoxybenzamide; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N- Isobutyl-2-methoxybenzamide; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N- cyclobutylbenzamide; 4-(2-(4-Acrylamidephenyl)-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]pyridine -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-7-cyano-2-(4-(2-fluoroacrylamide)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridine-3- base)-N-cyclobutylbenzamide; 4-(4-Amino-7-cyano-2-(4-(2-fluoroacrylamide)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridine-3- base)-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-Acrylamide-2-methoxyphenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridine-3 -yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(2-(4-Acrylamide-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-(2-(4-Acrylamide-2-methoxyphenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridine-3 -base)-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]pyridine-3- base)-N-isopropyl-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]pyridine-2- Base) benzene) acrylamide; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N- (2,2-difluorocyclopropyl)-2-methoxybenzamide; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N- (3-fluorocyclobutyl)-2-methoxybenzamide; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2- Methoxy-N-(1-methylcyclopropyl)benzamide; 4-(2-(4-Acrylamidephenyl)-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; 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; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N- (3,3-difluorocyclobutyl)-2-methoxybenzamide; 4-(2-(4-Acrylamidephenyl)-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- Pyrro[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-propenylpyridin-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-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N- (2,2-difluoroethyl)-2-methoxybenzamide; 4-(2-(1-Acrylylpyrrolidin-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-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N- ((1-fluorocyclopropyl)methyl)-2-methoxybenzamide; 4-(2-(4-Acrylamide-3-fluorophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) -N-cyclopropyl-2-methoxybenzamide; 4-(2-(4-Acrylamide-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-propenyl-2,5-dihydro-1H-pyrrol-3-yl)-4-amino-7-cyano-1-methyl-1H-pyrrole [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- Cyclopropyl-2-methoxybenzamide; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-(2-fluoroethyl)-1H-pyrrolo[3,2-c]pyridine-3- base)-N-cyclopropyl-2-methoxybenzamide; N-(4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) -2-methoxyphenyl)cyclopropanemethamide; 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; 4-(2-(4-Acrylamidephenyl)-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- Pyrro[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; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N -(2,2,2-trifluoroethyl)benzamide; N-(4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) -2-methoxyphenyl)cyclobutamide; N-(4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) -2-methoxyphenyl)cyclopentamide; 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-(2-(4-Acrylamide-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-propylamidophenyl)-1-methyl-1H-pyrrolo[3,2-c] Pyridin-2-yl)phenyl)acrylamide; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-(2-fluoroethyl)-1H-pyrrolo[3,2-c]pyridine-3- base)-N-(3,3-difluorocyclobutyl)-2-methoxybenzamide; 4-(2-(4-Acrylamide-2-fluorophenyl)-4-amino-7-cyano-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-(3 ,3-difluorocyclobutyl)-2-methoxybenzamide; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-isopropyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N -(3,3-difluorocyclobutyl)-2-methoxybenzamide; N-(4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) -2-methoxyphenyl)-N-methylcyclopropanemethamide; N-(4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) Phenyl)cyclopropanemethamide; N-(4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) -2-methoxyphenyl)-3,3-difluorocyclobutane-1-methamide; N-(4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) -2-methoxyphenyl)-1-methylcyclopropane-1-methamide; N-(4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) -2-methoxyphenyl)-1-fluorocyclopropane-1-methamide; N-(4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) -2-methoxyphenyl)-1-(trifluoromethyl)cyclopropane-1-methamide; 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-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) -2-methoxyphenyl)-2,2-difluorocyclopropane-1-methamide; N-(4-(4-amino-7-cyano-3-(4-(3-cyclopropylureido)-3-methoxyphenyl)-1-methyl-1H-pyrrolo[3 ,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(4-(cyclobutylamino)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2- Base)phenyl)acrylamide; N-(4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) -2-methoxyphenyl)azetidine-1-methamide; 4-(2-(4-Acrylamide-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-Acrylamidephenyl)-4-amino-7-cyano-1-(2-methoxyethyl)-1H-pyrrolo[3,2-c]pyridine- 3-yl)-N-(3,3-difluorocyclobutyl)-2-methoxybenzamide; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-(2-fluoroethyl)-1H-pyrrolo[3,2-c]pyridine-3- base)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-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-(pyrrolidin-1-yl)phenyl)-1H-pyrrolo[3,2-c]pyridine- 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-Acrylamidephenyl)-4-amino-7-cyano-1-(2-methoxyethyl)-1H-pyrrolo[3,2-c]pyridine- 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-7-cyano-1-methyl-3-(1-methyl-1H-indol-5-yl)-1H-pyrrolo[3,2-c]pyridine -2-yl)phenyl)acrylamide; N-(4-(4-amino-3-(benzo[b]thiophen-2-yl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridine-2- Base)phenyl)acrylamide; 4-(2-(4-Acrylamidephenyl)-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-Acrylamidephenyl)-4-amino-7-cyano-1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-c ]pyridin-3-yl)-2-methoxy-N-(2,2-difluoroethyl)benzamide; 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-(2-(4-Acrylamidephenyl)-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-Acrylamidephenyl)-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-7-cyano-3-(3-methoxy-4-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl) (yl)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-cyclopropyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N -Cyclopropyl-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]phenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)-3-fluorophenyl)-1-methyl Base-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 Base-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-7-cyano-3-(3-fluoro-4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)-1-methyl Base-1H-pyrrolo[3,2-c]pyridin-2-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- Pyrro[3,2-c]pyridin-2-yl)phenyl]acrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)-1H- Pyrro[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-7-cyano-3-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)-3-fluorophenyl)-1-methyl Base-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 Base-1H-pyrrole[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-pyrrole[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]pyridine -2-yl)-3-fluorophenyl)methacrylamide; 4-(4-amino-7-cyano-2-(2-fluoro-4-methacrylamidephenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridine-3- methyl)-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-pyrrole And[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-pyrrole And[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]pyridine-2- methyl)-3-fluorophenyl)methacrylamide; 4-(4-Amino-7-cyano-2-(2-fluoro-4-methacrylamidephenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridine-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]pyridine -2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-(pyridin-2-yloxy)phenyl)-1H-pyrrolo[3,2-c]pyridine -2-yl)phenyl]acrylamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((5-fluoropyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrole And[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 Base-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-pyrrole And[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- Pyrro[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-pyrrole And[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- Pyrro[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- Pyrro[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]pyridine-2- Base) benzene) acrylamide; N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl Base-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]pyridine -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- Pyrro[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 Base-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 Base-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 Base-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- Pyrro[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 base)phenyl)-1-methyl-1H-pyrrole[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-(tetrafluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3 ,2-c]pyridin-2-yl)phenylacrylamide; 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-pyrrole And[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- Pyrrole[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- Pyrro[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; N-(4-(4-amino-3-(3-chloro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H- Pyrro[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]pyridine-2- (base)-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-methylphenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl-1H- Pyrro[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- Pyrrole[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- Pyrro[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 Base-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 Base-1H-pyrrole[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 Base-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- Pyrro[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- Pyrro[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- Pyrro[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- Pyrro[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- Pyrro[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- Pyrro[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- Pyrro[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- Pyrro[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- Pyrro[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- Pyrro[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-enthiamide; 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-trifluoro Ethyl)-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 Base-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-pyrrole[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- Pyrro[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- Pyrro[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 Base-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- Pyrro[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- Pyrro[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 Base-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 Base-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)butan-2-amide; N-(4-(4-amino-3-(4-((5-chloro-4-(difluoromethyl)pyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl Base-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 Base-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- Pyrro[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 Base-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 Base-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 Base-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 Base-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- Pyrro[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 Base-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- Pyrro[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 Base-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- Pyrro[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 Base-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 Base-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorobenzene)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 or N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H- Pyrro[3,2-c]pyridin-2-yl)-3-fluorophenyl)-2-fluoroacrylamide.

The present invention further provides a pharmaceutical composition comprising at least one of the compounds represented by formula (I) and/or formula (II), and a pharmaceutically acceptable carrier.

In some embodiments of pharmaceutical compositions comprising compounds represented by formula (I) and/or formula (II) provided by the present invention, the pharmaceutical compositions comprise any one of compound numbers 1 to 270, and Pharmaceutically acceptable carrier.

In some embodiments of pharmaceutical compositions containing compounds represented by formula (I) and/or formula (II) provided by the present invention, the pharmaceutical compositions include any one of the compounds in Table 2, and a pharmaceutically acceptable carrier.

In some embodiments of pharmaceutical compositions containing compounds represented by formula (I) and/or formula (II) provided by the present invention, the pharmaceutical compositions include compound numbers 1, 2, 3, 4, 5, A compound of any one of 6, 7, 8, 9, 10, 11, 12 or 13, and a pharmaceutically acceptable carrier.

The present invention further provides a method for inhibiting FGFR2 signaling activity in a subject, comprising administering to a subject in need a therapeutically effective amount of a compound of formula (I) and/or formula (II) provided by the present invention, and a pharmaceutical composition thereof. .

In some specific embodiments, the method of inhibiting FGFR2 signaling activity in a subject includes administering to a subject in need a therapeutically effective amount of compounds No. 1 to Compound No. 270 provided by the present invention, and pharmaceutical compositions thereof.

In some specific embodiments, the method of inhibiting FGFR2 signaling activity in a subject includes administering to a subject in need a therapeutically effective amount of a compound described in any one of Table 2 of the present invention, and a pharmaceutical composition thereof.

In some specific embodiments of the method for inhibiting FGFR2 signaling activity in a subject, the method includes administering 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, A therapeutically effective amount of any of the compounds 11, 12 or 13, and pharmaceutical compositions thereof.

The present invention further provides a method for treating a disease in a subject, comprising administering to a subject in need of treatment a therapeutically effective amount of a compound described in any one of Formula (1) and/or Formula (II), and pharmaceutical combinations thereof The disease is cholangiocarcinoma, liver cancer, breast cancer, prostate cancer, lung cancer, thyroid cancer, gastric cancer, ovarian cancer, rectal cancer, endometrial cancer or urothelial cancer.

In some embodiments, the method of treating a disease in a subject, which is cholangiocarcinoma, includes administering to a subject in need of treatment a therapeutically effective amount of any one of Compound Nos. 1 to 270, and a pharmaceutical composition thereof, , liver cancer, breast cancer, prostate cancer, lung cancer, thyroid cancer, stomach cancer, ovarian cancer, rectal cancer, endometrial cancer or urothelial cancer.

In some specific embodiments, the method of treating a subject's disease includes administering to a subject in need of treatment a therapeutically effective amount of the compounds described in Table 2 provided by the present invention, and pharmaceutical compositions thereof, and the disease is Bile duct cancer, liver cancer, breast cancer, prostate cancer, lung cancer, thyroid cancer, stomach cancer, ovarian cancer, rectal cancer, endometrial cancer or urothelial cancer.

In some specific embodiments, the method of treating a subject's disease includes administering a therapeutically effective amount of 1, 2, 3, 4, 5, 6, 7, 8, 9 provided by the present invention to the subject in need of treatment. , 10, 11, 12 or 13 any compound, and pharmaceutical compositions thereof, the diseases are cholangiocarcinoma, liver cancer, breast cancer, prostate cancer, lung cancer, thyroid cancer, gastric cancer, ovarian cancer, rectal cancer, endometrial cancer or urothelial cancer.

The present invention further provides a method for treating a subject's disease regulated by FGFR2, comprising administering a therapeutically effective amount of a compound described in any one of formula (1) and/or formula (II) to a subject in need of treatment, and pharmaceutical compositions thereof, the diseases being cholangiocarcinoma, liver cancer, breast cancer, prostate cancer, lung cancer, thyroid cancer, gastric cancer, ovarian cancer, rectal cancer, endometrial cancer or urothelial cancer.

In some embodiments, methods for treating a subject with a disease modulated by FGFR2 include administering to a subject in need of treatment a therapeutically effective amount of any one of Compound Nos. 1 to 270, and pharmaceutical compositions thereof, said The disease is cholangiocarcinoma, liver cancer, breast cancer, prostate cancer, lung cancer, thyroid cancer, gastric cancer, ovarian cancer, rectal cancer, endometrial cancer or urothelial cancer.

In some specific embodiments, the method of treating a subject's disease regulated by FGFR2 includes administering to the subject in need of treatment a therapeutically effective amount of the compounds described in Table 2 provided by the present invention, and pharmaceutical compositions thereof, The disease is cholangiocarcinoma, liver cancer, breast cancer, prostate cancer, lung cancer, thyroid cancer, gastric cancer, ovarian cancer, rectal cancer, endometrial cancer or urothelial cancer.

In some embodiments, the method of treating a subject's disease regulated by FGFR2 includes administering a therapeutically effective amount of 1, 2, 3, 4, 5, 6, 7 provided by the present invention to the subject in need of treatment. , 8, 9, 10, 11, 12 or 13 any compound, and pharmaceutical compositions thereof, the diseases are cholangiocarcinoma, liver cancer, breast cancer, prostate cancer, lung cancer, thyroid cancer, gastric cancer, ovarian cancer, rectal cancer, Endometrial cancer or urothelial cancer.

In some embodiments of the method of treating a disease in a subject, the disease is cholangiocarcinoma.

In some embodiments of the method of treating a disease in a subject, the cholangiocarcinoma is intrahepatic cholangiocarcinoma.

In some embodiments of the method of treating a disease in a subject, the disease is liver cancer.

In some embodiments of the method of treating a disease in a subject, the liver cancer is hepatocellular carcinoma.

In some embodiments of the method of treating a disease in a subject, the disease is lung cancer.

In some embodiments of the method of treating a disease in a subject, the lung cancer is pulmonary squamous cell carcinoma or non-small cell lung cancer.

Representative compounds among the compounds represented by the above formula (I) are shown in Examples 1 to 13, Table 2 and Table 3.

The compounds provided by the invention have high activity against the kinase FGFR2 at the enzyme level and in cell experiments, and are highly selective for both FGFR1 and FGFR3.

Many of the compounds provided by the invention exhibit good to excellent exposure in rat PK experiments.

definition

The following description is made with the understanding that the present invention is to be considered an example of the claimed subject matter and is not intended to limit the appended claims to the specific embodiments shown. The headings used in the invention are provided for convenience and should not be deemed to limit the requested items in any way. There is no intention to limit the appended claims to the specific embodiments shown. The headings used in this disclosure are provided for convenience and should not be construed as limiting the claim in any way. An embodiment described under any heading may be combined with an embodiment described under any other heading.

Unless otherwise defined, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art. It must be noted that, as used herein, the singular forms "a," "and" and "the" include plural referents unless the context clearly dictates otherwise. Thus, "the compound" includes a plurality of similar compounds, and "the assay" includes one or more assays, and so on.

Unless the context indicates otherwise, the following words, phrases and symbols in the present invention are generally intended to have the meanings described below.

Unless otherwise stated in the present invention, for convenience, a dash "-" is used at the front or end of a chemical group to indicate the point of attachment of the substituent. For example, -OH indicates attachment through a carbon atom; chemical groups may or may not be described with one or more dashes without losing their ordinary meaning. A wavy line drawn through a line in a structure represents the attachment point of a group. The order in which chemical groups are written or named does not indicate or imply directionality unless chemically or structurally required. The solid line coming out of the center of the ring indicates that the point of attachment of the substituents on the ring can be on any ring atom.

Unless otherwise stated in the present invention, the first code "C _mn " means that the following groups have m to n carbon atoms. For example, "C _1-6 alkyl" means an alkyl group having 1 to 6 carbon atoms. Similarly, the term "mn-membered" ring, where m and n represent an integer range from m to n, such as "3-7 membered heterocycle" refers to a ring containing 3-7 atoms, up to 80% of which may be heteroatoms, Such as nitrogen, oxygen or sulfur, the remaining atoms are carbon.

The term "aliphatic" or "aliphatic group", unless otherwise specified, as used herein, refers to a linear (i.e., unbranched) or branched chain that is fully saturated or contains one or more unsaturated units. , a substituted or unsubstituted hydrocarbon chain, or a monocyclic or bicyclic hydrocarbon that is fully saturated or contains one or more unsaturated units, but is not aromatic (also referred to herein as "carbocyclic" or "alicyclic"), It has a single point of connection to the rest of the molecule. Unless otherwise stated, aliphatic groups contain 1-6 aliphatic carbon atoms. In some embodiments, aliphatic groups contain 1-5 aliphatic carbon atoms. In other embodiments, the aliphatic group contains 1-4 aliphatic carbon atoms. In still other embodiments, the aliphatic group contains 1-3 aliphatic carbon atoms, and in other embodiments, the aliphatic group contains 1-2 aliphatic carbon atoms. In some examples, "cycloaliphatic"("carbocycle") refers to a monocyclic _C3 - _C6 hydrocarbon that is fully saturated or contains one or more unsaturated units but is not aromatic, which has Single point of connection. Suitable aliphatic groups include, but are not limited to, linear or branched chain, substituted or unsubstituted alkyl, alkenyl, alkynyl and hybrid groups thereof, such as (cycloalkyl) alkyl, (cycloalkenyl) )alkyl or (cycloalkyl)alkenyl.

In addition, some commonly used alternative chemical names may or may not be used. For example, a divalent group, a divalent "alkyl" group, a divalent "aryl" group, etc. may also be referred to as an "alkylene" group, an "alkylene" group, or an alkyl group, respectively. group; "arylene" group, "aryl" group, or aryl group; "phenyl" group or "phenylene" group.

"Compounds provided herein" or "compounds described herein" or "compounds disclosed herein" or "compounds of the present disclosure" refer to compounds represented by formula (I) and/or (II).

In some instances, the term "about" for the value or parameter itself indicates an amount that includes ±10%, ±5%, or ±1%. Furthermore, the term “relating to X” includes descriptions of “X”.

"Adjacent atoms" as used herein refers to atoms that are immediately adjacent to each other. For example, in "C1-C2-C3-C4", the C1 atom is adjacent to the C2 atom, the C2 atom is adjacent to the C1 and C3 atoms, and so on.

"Optional" or "optionally" means that the subsequently described event or circumstance may or may not occur, and that the description includes both instances in which the stated event or circumstance occurs and instances in which it does not occur. Furthermore, the term "optionally substituted" means that any one or more hydrogen atoms on the specified atom or group may or may not be substituted with a moiety other than hydrogen.

"Substituted" means that one or more hydrogen atoms on a designated atom or group are replaced by one or more substituents other than hydrogen, provided that the normal valency of the designated atom is not exceeded. For example, one or more hydrogens of alkyl, alkylene, alkenyl, alkenyl, OH or _NH2 , etc. may be substituted with one or more substituents. Substituents include, but are not limited to, alkyl, alkenyl, alkynyl, alkoxy, acyl, amino, acylamino, amidino, aryl, azido, carbamate, carboxyl, carboxyl ester, cyano, Guanidino, halogen, haloalkyl, heteroalkyl, heteroaryl, heterocyclyl, hydroxyl, hydrazino, imino, oxo, nitro, alkylsulfenyl, sulfonic acid, alkylsulfonyl, Thiocyanates, thiols, thiones or combinations thereof. Similar indefinite structures obtained by substituting substituents with further defined substituents appended to infinity are not intended to be included herein (e.g., a substituted aryl group with a substituted alkyl group, itself substituted with a substituted aryl group, which is further substituted heteroalkyl substitution, etc.). Unless otherwise stated, the maximum number of consecutive substitutions in the compounds described herein is three. For example, consecutive substitution of a substituted aryl group by two other substituted aryl groups is limited to ((substituted aryl) substituted aryl) substituted aryl. Similarly, the above definition is not intended to include disallowed substitution patterns (eg, methyl substituted with 5 fluorine or heteroaryl with two adjacent oxygen ring atoms). Such disallowed alternative modes are well known to those skilled in the art. Whenever used to modify a chemical group, "substituted" may describe other chemical groups as defined herein. For example, the term "substituted aryl" includes, but is not limited to, "alkylaryl." Unless otherwise stated, if a group is described as optionally substituted, then any substituents of that group are themselves unsubstituted.

As used in the present invention, the term "C _1-6 (or C _1-4 or C _1-3 ) divalent saturated or unsaturated straight or branched hydrocarbon chain" means a straight or branched hydrocarbon chain as defined in the present invention. Divalent alkylene, alkenylene and alkynyl chains.

The term "alkylene" as used in the present invention, unless otherwise stated, refers to a divalent alkyl group. "Alkylene chain" is polymethylene, ie -( _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 refers to a polymethylene group in which one or more methylene hydrogen atoms are replaced by a substituent. Suitable substituents include substituted fatty acid groups as described below.

The term "alkenyl" used in the present invention, unless otherwise stated, refers to a divalent alkenyl group. Substituted alkenyl chains are polymethylene groups containing at least one double bond in which one or more hydrogen atoms are replaced by a substituent. Suitable substituents include substituted fatty acid groups as described below.

The terms "alkylene", "arylene", "cycloalkyl", "heteroarylene", "heterocycloalkylene" and other similar terms with the tail code "-ene" used in the present invention Terms, unless otherwise stated, refer to the divalently bonded version of the tail-modified group. For example, "alkylene" is a divalent alkyl group attached to the group to which it is attached.

The term "alkyl", as used herein, unless otherwise specified, refers to a monovalent aliphatic hydrocarbon radical having a straight chain, a branched chain, a monocyclic moiety, or a polycyclic moiety, or a combination thereof, wherein the radical is optionally replaced by One or more carbon substitutions of linear, branched, monocyclic or polycyclic moieties, or combinations thereof, are substituted on each carbon, wherein the one or more substituents are independently C ₁ -C ₆ alkyl. "Alkyl" includes methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, cyclopropyl, cyclobutyl, cyclobutyl, Pentyl, cyclohexyl, cycloheptyl, norbornyl, "butyl" includes n-butyl (i.e. -(CH ₂ ) ₃ CH ₃ ), sec-butyl (i.e. -CH(CH ₃ )CH ₂ CH ₃ ) , isobutyl (i.e. -CH ₂ ) ₂ CH ₃ ), etc. "Propyl" includes n-propyl (ie -(CH ₂ ) ₂ CH ₂ ) and isopropyl (ie -CH(CH ₃ ) ₂ ), and pentyl includes 2-pentyl, isopentyl or neopentyl.

The term "alkenyl" used in the present invention, unless otherwise stated, refers to a 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 of 2 to 4 carbon atoms (i.e., C _2-4 alkenyl). Examples of alkenyl groups include vinyl, propenyl, butadienyl (including 1,2-butadienyl and 1,3-butadienyl).

The term "alkynyl" used in the present invention, unless otherwise stated, refers to a group containing at least one carbon-carbon triple bond ( ), and an aliphatic group having 2 to 10 carbon atoms (i.e., C _2-10 alkynyl) or 2-4 carbon atoms (i.e., C _2-4 alkynyl), etc. The term "alkynyl" also includes groups having one triple bond and one double bond.

The term "alkoxy" used in the present invention refers to "-O-alkyl", such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy , sec-butoxy, n-pentyloxy, n-hexyloxy and 1, 2-dimethylbutoxy. The term "haloalkoxy" refers to an alkoxy group as described above, in which one or more hydrogen atoms are replaced by halogen.

The term "lower alkyl" used in the present invention refers to a C _1-4 linear or branched alkyl group. Typical lower alkyl groups are methyl, ethyl, propyl, isopropyl, butyl, isobutyl and tert-butyl.

The term "lower haloalkyl" used in the present invention refers to a C _1-4 linear or branched alkyl group substituted by one or more halogen atoms.

The term "heteroatom" as used herein refers to one or more of oxygen, sulfur, nitrogen, phosphorus or silicon (including any oxidized form of nitrogen, sulfur, phosphorus or silicon; any quaternized form of basic nitrogen or heterocyclic substituted nitrogen, such as N (eg 3,4-dihydro-2H-pyrrolyl), NH (eg pyrrolidinyl) or NR+ (eg N-substituted pyrrolidinyl)).

The term "unsaturated" as used herein refers to a moiety having one or more units of unsaturation.

The term "partially unsaturated" used in the present invention in the description of rings, unless otherwise defined, refers to the component rings in a monocyclic ring or a polycyclic (such as bicyclic, tricyclic, etc.) ring system, wherein A ring segment contains at least one unsaturation that is not aromatic in addition to the unsaturation provided by the ring itself. Examples of partially unsaturated rings include, but are not limited to, 3,4-dihydro-2H-pyran, 3-pyrroline, 2-thiazoline, and the like. Among them, the partially unsaturated ring is part of the polycyclic system. The other component rings in the polycyclic system can be saturated, partially unsaturated or aromatic, but the connection point of the polycyclic system is at the partially unsaturated component ring. superior. For example, unless otherwise defined, 1,2,3,4-tetrahydroquinoline is a partially unsaturated ring if its point of attachment is through the piridine ring, for example:

The term "saturated" used in the present invention in the description of rings, unless otherwise defined, refers to a 3-10-membered monocyclic ring or a 7-14-membered polycyclic (such as bicyclic, tricyclic, etc.) ring system. wherein a single ring or a component ring serving as a point of attachment to a polycyclic ring system contains no additional unsaturation beyond that provided by the ring itself. Examples of monocyclic saturated rings include, but are not limited to, azetidine, oxane, cyclohexane, and the like. When a saturated ring is part of a polycyclic system, the other component rings in the polycyclic system may be saturated, partially unsaturated, or aromatic, but the point of attachment to the polycyclic system is on the saturated component ring. For example, unless otherwise defined, 2-azaspiro[3.4]oct-6-ene is a saturated ring if its point of attachment is through the azadiamino ring, for example:

The term "carboxyl" as used in the present invention refers to the group -C(=O)R, where R is hydrogen, alkyl, cycloalkyl, heterocyclyl, aryl, heteroalkyl or heteroaryl, where Each can optionally be replaced. The acyl group includes formyl group, acetyl group, cyclohexylcarbonyl group, cyclohexylmethylcarbonyl group, benzyl group and the like.

The term "amide" as used in the present invention refers to the "C-amide" group referring to the group -C(=O)NR ^a R ^b and the "C-amide" group referring to the group -NR ^a C(=O)R ^b N-amide" group, wherein R ^a and R ^b are independently selected from hydrogen, alkyl, aryl, haloalkyl, heteroaryl, cycloalkyl and heterocyclyl; and each of them can be optionally selected and replace.

The term "amino" used in the present invention refers to the group -NR ^a R ^b , where R ^a and R ^b are independently selected from hydrogen, alkyl, haloalkyl, aryl, heteroaryl, cycloalkyl and heterocyclyl; And each of them can be selected and replaced at will.

The term "aryl" as used in the present invention refers to an aromatic carbocyclic group having one isolated ring (eg, monocyclic) or multiple rings (eg, bicyclic or tricyclic), including fused systems. As examples in the present invention, the aryl group has 6-20 ring carbon atoms (ie, C _6-20 aryl group), 6-12 carbon ring atoms (ie, C _6-12 aryl group), etc. Some examples of aryl groups include phenyl, naphthyl, fluorenyl, and anthracenyl. In the present invention, aryl does not include and does not overlap in any way with heteroaryl as defined below. If one or more aryl groups are fused to a heteroaromatic ring, the resulting ring system is heteroaryl.

The term "cyano" or "carbonitrile" group as used herein means -CN.

The term "cycloalkyl" used in the present invention refers to a saturated or partially saturated cyclic alkyl group having a single or multiple rings, including fused rings, bridged rings and spiro ring systems. The term "cycloalkyl" also includes cycloalkenyl (ie, cyclic groups having at least one double bond). The cycloalkyl group has 3-20 ring carbon atoms (i.e. C _3-20 cycloalkyl), 3-8 ring carbon atoms (i.e. C _3-8 cycloalkyl) or 3-5 ring carbon atoms (i.e. C _3-5 cycloalkyl) etc. Examples of "cycloalkyl" in the present invention also include cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

The term "fused ring" as used herein refers to a ring bonded to adjacent rings.

The term "spiro" as used herein refers to a ring substituent connected by two bonds on the same carbon atom. Some examples of spirocyclic groups include 1,1-diethylcyclopentane, dimethyldioxolane, and 4-benzyl-4-methylpyridine, where cyclopentane and pyridine are respectively spirocyclic substituents.

"Halogen" includes fluorine (F), chlorine (Cl), bromine (Br) and iodine (I).

"Deuterium" and "D" both refer to deuterium.

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

The term "haloalkyl" as used herein includes unbranched or branched alkyl groups as described above, in which one or more hydrogen atoms are replaced by halogen. If a residue is substituted by more than one halogen, this may be indicated by a first code corresponding to the number of attached halogen moieties. Dihaloalkyl and trihaloalkyl refer to alkyl groups substituted by two ("di") or three ("tri") halogenated groups, which may be, but are not necessarily, the same halogen. Examples of haloalkyl groups include difluoromethyl (-CHF ₂ ) and trifluoromethyl (-CF ₃ ).

The term "heteroaryl" used in the present invention refers to a monocyclic, polycyclic or multiple fused-cyclic aromatic group in which one or more ring heteroatoms are independently selected from N, O and S. Examples in the present invention include: heteroaryl groups including 1 to 20 carbon ring atoms (C _1-20 heteroaryl), 3 to 12 carbon ring atoms (C _3-12 heteroaryl), etc., and those independently selected Number of ring heteroatoms from N, O or S. Heteroaryl groups include pyrimidinyl, purinyl, pyridyl, pyridazinyl, benzothiazolyl and pyrazolyl. The term "heteroaryl" does not include or overlap with "aryl" as defined above.

The term "heterocyclic compound" or "heterocycle" used in the present invention refers to selecting at least one from boron (B), nitrogen (N), oxygen (O), phosphorus (P) and sulfur (S) as the heterocyclic atom. of non-aromatic cyclic alkyl groups. "Heterocycle" or "heterocycle" includes heterocycloalkenyl (heterocyclyl having at least one double bond). Heterocycles may be monocyclic or polycyclic, wherein polycyclic rings may be fused, bridged, or spirocyclic. As used herein, heterocyclyl has 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 carbocyclic rings Atom (i.e. C _3-6 heterocyclyl); heterocyclic groups with 1 to 5 ring heteroatoms selected from B, N, O, P or S include pyrrolidinyl, pyridinyl, pyridinyl, oxygen Heterocyclyl, dioxaheterocyclyl, azacyclyl and morpholinyl. The term "bridged heterocyclyl" refers to a 4-10 membered ring moiety having at least one heteroatom attached at two non-adjacent atoms of the heterocyclyl to one or more (e.g., 1 or 2) 4-10 membered ring moieties. A membered ring moiety in which each heteroatom is 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 "spirocarbocyclyl" or "spirocarbocyclyl" includes bicyclic and tricyclic ring systems and refers to ring systems in which a three- to ten-membered carbocyclyl group has one or more additional rings, wherein one The or more additional rings are three- to ten-membered carbocyclyl groups, wherein a single atom of one or more of the additional rings is also an atom of the three- to ten-membered carbocyclyl group. Also as used herein, the term "fused heterocyclyl" refers to a three- to ten-membered cyclic moiety attached at two adjacent atoms of the heterocyclyl group to one or more (eg, 1 or 2) three- to ten-membered cyclic moieties. The membered cyclic moiety has at least one heteroatom, where each heteroatom is 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 "heterocycle" are used interchangeably and include mono-, bridged-, spiro- or fused-carbocycles and combinations thereof. In some embodiments, heterocyclyl is substituted with carbonyl.

The term "carbocyclyl" or "carbocycle" refers to a non-aromatic cyclic aliphatic group that does not contain any ring heteroatoms, where, unless otherwise stated, "carbocyclyl" or "carbocycle" refers to a saturated or Partially saturated ring, for example, in some embodiments, "carbocyclyl" or "carbocycle" refers to a partially saturated ring in a particular case. "Carbocyclyl" or "carbocycle" includes carbocyclyl (ie, carbocyclyl having at least one double bond). Carbocyclic rings may be monocyclic or polycyclic, wherein polycyclic rings may be fused, bridged, or spirocyclic. The carbocyclic rings described herein have 3-14 carbon ring atoms (i.e., C _3-14 carbocyclic ring or C _3-14 carbocyclic ring), 3-8 carbon ring atoms (i.e., C _3-8 carbocyclic ring) or 3- 6 carbon ring atoms (i.e. C _3-6 carbocyclic rings); examples of carbocyclic groups include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. The term "bridged carbocycle" refers to a three- to ten-membered cyclic moiety connected to one or more (e.g., 1 or 2) three- to ten-membered cyclic moieties at two non-adjacent carbon atoms of the carbocyclyl group . As used herein, "bridged carbocyclyl" or "bridged carbocycle" includes bicyclic and tricyclic ring systems. Also as used herein, the term "spirocarbocyclyl" or "spirocarbocyclyl" includes bicyclic and tricyclic ring systems and refers to ring systems in which a three- to ten-membered carbocyclyl group has one or more additional rings, wherein one The or more additional rings are three- to ten-membered carbocyclyl groups, wherein a single atom of one or more of the additional rings is also an atom of the three- to ten-membered carbocyclyl group. Also as used herein, the term "fused carbocyclyl" or "condensed carbocyclyl" includes bicyclic and tricyclic ring systems and refers to a carbocyclyl group with one or more three- to Ten-membered cyclic moiety (eg, 1 or 2) Three to ten-membered cyclic moiety. As used herein, the terms "carbocyclyl" and "carbocycle" are used interchangeably and include single, bridged, spiro or fused carbocycles and combinations thereof.

"Hydroxy" or "hydroxyl" refers to the group -OH.

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

The term "sulfonyl" refers to the group -S(O) ₂ R ^a , where R ^a is alkyl, haloalkyl, heterocyclyl, cycloalkyl, heteroaryl or aryl. Some examples of sulfonyl groups are methanesulfonyl, ethylsulfonyl, benzenesulfonyl and toluenesulfonyl.

Whenever a group terminates in a separately bonded nitrogen atom, the group represents a -NH group unless otherwise stated. Similarly, unless otherwise stated, the presence of hydrogen atoms is implied and considered to be present where necessary to complete the valency or provide stability based on the knowledge of one skilled in the art.

"Optional", "any" or "optionally" means that the subsequently described event or circumstance may or may not occur, and that the description includes instances where the stated event or circumstance occurs and instances where it does not. Furthermore, the term "optionally substituted" means that any one or more hydrogen atoms on the specified atom or group may or may not be substituted with a suitable substituent other than hydrogen. Substituents may be the same or different at each position. Combinations of substituents contemplated by the present invention are preferably those which result in the formation of stable or chemically feasible compounds. As used herein, the term "stable" as disclosed herein means substantially unchanged when subjected to conditions permitting its production, testing, and in certain embodiments its recovery, purification, and use for one or more purposes. compound of.

"Substituted" means that one or more hydrogen atoms on a designated atom or group are replaced by one or more substituents other than hydrogen, provided that the normal valency of the designated atom is not exceeded. Substituents include, but are not limited to, alkyl, alkenyl, alkynyl, alkoxy, acyl, amino, acylamino, amidino, aryl, azido, carbamate, carboxyl, carboxyl ester, cyano, Guanidino, halogen, haloalkyl, heteroalkyl, heteroaryl, heterocyclyl, hydroxyl, hydrazino, imino, oxo, nitro, alkylsulfenyl, sulfonic acid, alkylsulfonyl, Thiocyanates, thiols, thiones or combinations thereof. Similar indefinite structures obtained by substituting substituents with further defined substituents appended to infinity are not intended to be included herein (e.g., a substituted aryl group with a substituted alkyl group, itself substituted with a substituted aryl group, which is further substituted heteroalkyl substitution, etc.). Unless otherwise stated, the maximum number of consecutive substitutions in the compounds described herein is three. For example, consecutive substitution of a substituted aryl group by two other substituted aryl groups is limited to ((substituted aryl) substituted aryl) substituted aryl. Similarly, the above definition is not intended to include disallowed substitution patterns (eg, methyl substituted with 5 fluorine or heteroaryl with two adjacent oxygen ring atoms). Such disallowed alternative modes are well known to those skilled in the art. Whenever used to modify a chemical group, "substituted" may describe other chemical groups as defined herein. For example, the term "substituted aryl" includes, but is not limited to, "alkylaryl." Unless otherwise stated, if a group is described as optionally substituted, then any substituents of that group are themselves unsubstituted.

In some cases, "substituted alkyl" refers to an alkyl group having one or more substituents including hydroxyl, halogen, amino, alkoxy, cycloalkyl, heterocyclyl, aryl, and Heteroaryl. In other instances, "substituted cycloalkyl" refers to a cycloalkyl group having one or more substituents, including alkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, amino , alkoxy, halogen, oxo and hydroxyl; "substituted heterocyclyl" refers to a heterocyclyl group with one or more substituents, including alkyl, amino, haloalkyl, heterocyclyl, cycloalkyl, aromatic radical, heteroaryl, alkoxy, halogen, oxo and hydroxy; the term "substituted aryl" refers to an aryl group with one or more substituents, including halogen, alkyl, amino, haloalkyl, cycloalkyl radical, heterocyclyl, heteroaryl, alkoxy and cyano; the term "substituted heteroaryl" refers to a heteroaryl with one or more substituents, including halogen, amino, alkyl, haloalkyl, Cycloalkyl, aryl, heterocyclyl, heteroaryl, alkoxy and cyano, the term "substituted sulfonyl" refers to the group -S(O) ₂ R, where R is replaced by one or more Substituents include alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl. In other cases, one or more substituents may be further substituted by halogen, alkyl, haloalkyl, hydroxy, alkoxy, cycloalkyl, heterocyclyl, aryl or heteroaryl, each of which is substituted . In other cases, the substituent may be further substituted by halogen, alkyl, haloalkyl, alkoxy, hydroxy, cycloalkyl, heterocyclyl, aryl or heteroaryl, each of which is unsubstituted.

In some embodiments, substituted cycloalkyl, substituted heterocyclyl, substituted aryl and/or substituted heteroaryl, including cycloalkyl, heterocyclyl, aryl and/or heteroaryl, With substituents on the ring atoms, cycloalkyl, heterocyclyl, aryl and/or heteroaryl groups are attached to the remainder of the compound. For example, in the following section, the benzene ring is replaced by a m-chloro group:

The compounds disclosed herein, or pharmaceutically acceptable salts thereof, may contain one or more asymmetric centers, thereby giving rise to enantiomers, diastereoisomers and other stereoisomeric forms that can be determined according to absolute stereochemistry Defined as (R)- or (S)- or, as an amino acid, (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 can be prepared using chiral synthons or chiral reagents or resolved by conventional techniques. For example, chromatography and fractional crystallization. Traditional techniques for the preparation, separation of individual enantiomers include chiral synthesis from suitable optically pure precursors or resolution of racemates (or salts or derivatives) using, for example, chiral high pressure liquid chromatography (HPLC). racemate). When compounds disclosed herein contain alkenyl double bonds or other centers of geometric asymmetry, these compounds include E and Z geometric isomers unless otherwise stated. Likewise, all tautomeric forms are intended to be included. Where a compound is represented in its chiral form, it is understood that embodiments include, but are not limited to, the specific diastereomeric or enantiomerically enriched forms. Where chirality is not specified but is present, it is to be understood that the examples are intended to include the specific diastereomers or enantiomerically enriched forms or racemic or proportional mixtures of such compounds. A "proportional mixture" is a mixture of stereoisomers in a ratio other than 1:1, but a "proportional" mixture.

The term "stereoisomers" refers to compounds containing the same atoms bonded by the same bonds but having different three-dimensional structures, which are not interchangeable. This disclosure contemplates various stereoisomers and mixtures thereof, and includes "enantiomers" which refers to two stereoisomers whose molecules are non-superimposable mirror images of each other.

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. The ratio is not a 1:1 mixture of enantiomers, but a "ratio" mixture.

The term "diastereomer" means stereoisomers that have at least two asymmetric atoms but are not mirror images of each other.

"Tautomer" refers to the transfer of a proton from one atom of a molecule to another atom of the same molecule. This disclosure includes tautomers of any compound provided herein.

As used herein, an "effective amount," "sufficient amount," or "therapeutically effective amount" is an amount of a compound sufficient to achieve beneficial or desired results, including clinical results. Accordingly, an effective amount may be sufficient, for example, to reduce or ameliorate the severity and/or duration of a disorder associated with FGFR2 signaling or one or more symptoms thereof, to prevent the progression of, or enhance, a disorder or symptom associated with a disorder associated with FGFR2 signaling. or otherwise improve the preventive or therapeutic efficacy of another therapy. An effective amount also includes an amount of a compound that avoids or substantially lessens undesirable side effects.

As used herein and as is known in the art, "treatment" is a method used to obtain 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, reduction in the severity of a disease or illness, stabilization (i.e., non-worsening) of a disease or illness, prevention of the spread of a disease or illness, or progression of a disease or illness. Delay or slowdown, improvement or alleviation and alleviation (whether partial or total) of a disease or painful condition, whether detectable or undetectable. "Treatment" may also mean prolonging survival compared to expected survival without treatment. In some embodiments, treatment may be performed after one or more symptoms have developed. In other embodiments, treatment can be performed without symptoms. For example, susceptible individuals may be treated before symptoms develop (e.g., based on history of symptoms and/or based on genetic or other predisposing factors). Treatment can also be continued after symptoms disappear, for example to prevent or delay their recurrence.

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

Some of the compounds disclosed herein exist as tautomers. Tautomers are in equilibrium with each other. For example, amide-containing compounds may exist in equilibrium with imidic acid tautomers. Regardless of which tautomer is shown, and regardless of the nature of the equilibrium between the tautomers, one of ordinary skill in the art understands that these compounds include the amide and imide tautomers. Thus, amide-containing compounds are understood to include their imide tautomers. Likewise, imide-containing compounds are understood to include their amide tautomers.

The interaction of solvents and compounds forms "solvates". As used herein, solvates also include solvates of salts of the disclosed compounds and hydrates of the compounds provided herein.

Any formulas or structures provided herein also represent unlabeled as well as isotopically labeled forms of the compounds. Isotopically labeled compounds have the same structure as depicted by the formulas given herein, except that one or more atoms are replaced by atoms of selected atomic qualities or mass numbers. Examples of isotopes include isotopes such as carbon ( ^11C , ^13C , ^14C ), nitrogen ( ^15N ), oxygen ( ^17O , ^18O ), phosphorus ( ^31P , ^32P ), fluorine ( ^18F ), chlorine ( ³⁶ Cl) and isotope of iodine ( ¹²⁵ I). Isotopically labeled compounds can 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 tissue distribution analysis of drugs or substrates or in patients. Radiation therapy.

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

The term "pharmaceutically acceptable salt" refers to a salt prepared from a pharmaceutically acceptable non-toxic acid. When the compounds of the present invention are basic, their corresponding salts may be conveniently prepared from pharmaceutically acceptable nontoxic acids, including inorganic and organic acids. Since the compounds of formula I and/or 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 ( % by weight).

The pharmaceutical composition of the present invention contains a compound represented by formula I and/or II or a pharmaceutically acceptable salt thereof as an active ingredient, a pharmaceutically acceptable carrier and optional other therapeutic ingredients or adjuvants. Modes of administration of the active ingredient include compositions suitable for oral, rectal, topical and parenteral (including subcutaneous, intramuscular and intravenous) administration, although the most appropriate route in any given case will depend on the particular host and the nature and severity of the condition targeted. The pharmaceutical compositions may conveniently be presented in unit dosage form and prepared by any method well known in the pharmaceutical art.

In practice, the compounds represented by formulas I and/or II of the present invention, or their prodrugs or metabolites or their pharmaceutically acceptable salts, can be closely mixed with pharmaceutical carriers according to conventional pharmaceutical compounding techniques as active ingredient combinations. The carrier may take a variety of forms depending upon the form of preparation desired for administration, such as oral or parenteral (including intravenous). Thus, the pharmaceutical compositions of the present invention may be in the form of discrete dosage forms suitable for oral administration, such as capsules, capsules or tablets, each containing a predetermined amount of the active ingredient. Furthermore, the compositions may be presented in the form of powders, granules, solutions, suspensions in aqueous solutions, non-aqueous liquids, oil-in-water emulsions, or water-in-oil liquid emulsions. In addition to the above-mentioned common dosage forms, the compounds represented by formula I and/or II or their pharmaceutically acceptable salts can also be administered through controlled release devices and/or delivery devices. The compositions can be prepared by any pharmaceutical method. Generally, such methods include the step of bringing into association the active ingredient with the carrier which constitutes one or more necessary ingredients. In general, the compositions are prepared by uniformly and intimately admixing the active ingredient with liquid carriers or finely divided solid carriers, or both. The product can then be easily shaped to the desired appearance.

Therefore, the pharmaceutical composition of the present invention may include a pharmaceutically acceptable carrier and a compound or pharmaceutically acceptable salt represented by Formula I and/or II. Compounds of Formula I and/or II or pharmaceutically acceptable salts thereof may also be included in pharmaceutical compositions in combination with one or more other therapeutically active compounds.

The pharmaceutical carrier used may be solid, liquid or gas. Examples of solid carriers include lactose, clay, sucrose, talc, gelatin, agar, pectin, gum arabic, magnesium stearate and stearic acid. Examples of liquid carriers are syrup, peanut oil, olive oil and water. Examples of gaseous carriers include carbon dioxide and nitrogen. In preparing compositions for oral dosage form, any convenient pharmaceutical medium may be employed. For example, water, glycols, oils, alcohols, flavors, preservatives, colorants, etc. can 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, disintegrants, etc. can be used to form oral solid preparations such as powders, capsules and tablets. Because of their ease of administration, tablets and capsules are preferred oral dosage units in which solid pharmaceutical carriers are used. Optionally, tablets may be coated by standard aqueous or non-aqueous techniques.

Tablets containing the compositions of the invention may be prepared by compression or moulding, 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 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 active ingredient, and each cachet or capsule preferably contains from about 0.05 mg to about 5 g of active ingredient. For example, formulations for oral administration to humans may contain from about 0.5 mg to about 5 g of active ingredient compounded with an appropriate and convenient amount of carrier material, which may vary as a percentage of the total composition from about 0.05% to about 95% . Unit dosage forms typically contain from about 0.01 mg to about 2 g of active ingredient.

Pharmaceutical compositions of the invention suitable for parenteral administration may be prepared as solutions or suspensions of the active compounds in water. Suitable surfactants may be included, such as hydroxypropylcellulose. Dispersions can also be prepared in glycerol, liquid polyethylene glycols, and mixtures thereof in oils. Additionally, preservatives may be included to prevent harmful growth of microorganisms.

Pharmaceutical compositions of the invention suitable for injectable use include sterile aqueous solutions or dispersions. Additionally, the compositions may 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 must flow efficiently to facilitate injection. Pharmaceutical compositions must be stable under the conditions of manufacture and storage; therefore, they are preferably stored in a manner that is free from the contaminating effects of microorganisms such as bacteria and fungi. The carrier may be a solvent or dispersion medium containing, for example, water, ethanol, polyols (eg glycerol, propylene glycol and liquid polyethylene glycol), vegetable oils and suitable mixtures thereof.

The pharmaceutical composition of the present invention can be used in a form suitable for topical administration, such as aerosol, cream, ointment, lotion, dust-removing powder, etc. Additionally, the compositions may be in a form suitable for use in transdermal devices. These preparations can be prepared by conventional processing methods using the compounds represented by formula (I) and/or formula (II) of the present invention or pharmaceutically acceptable salts thereof. For example, a cream or ointment is prepared by mixing a hydrophilic material and water and about 0.05 wt% to about 10 wt% of the compound to produce a cream or ointment with the desired consistency.

The pharmaceutical compositions of the present invention may be in a form suitable for rectal administration, wherein the carrier is a solid. Preferably the mixture is formed into 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 a softened or molten carrier and then cooling and shaping in a mould.

In addition to the above-mentioned carrier ingredients, the above-mentioned pharmaceutical preparations may include one or more additional carrier ingredients, as appropriate, such as diluents, buffers, flavoring agents, binders, surfactants, thickeners, lubricants, preservatives (including antioxidants) wait. In addition, other adjuvants may be included to render the formulation isotonic with the blood of the intended recipient. The composition containing the compound represented by Formula I and/or Formula II or a pharmaceutically acceptable salt thereof may also be prepared in the form of a powder or liquid concentrate.

Typically, dosage levels of about 0.001 mg/kg to about 150 mg/kg of body weight per day may be used to treat the conditions described above, or about 0.05 mg to about 7 g per patient per day. For example, cancers, diseases and disorders of the immune system can be effectively treated by administering about 0.001 to 50 mg of compound per kilogram of body weight per day, or about 0.05 mg to about 3.5 g of compound per patient per day.

It is understood, however, that the specific dosage level for any particular patient will depend on a variety of factors, including age, weight, general health, sex, diet, timing of administration, route of administration, excretion rate, combination of drugs, and the specific disease being treated severity, etc.

The term "disease" refers to any disease, ailment, disease, symptom or condition, and may be used interchangeably with the terms "disorder" or "condition".

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 cancer, uterine cancer, brain tumor, cervical cancer, colorectal cancer, esophageal cancer, endometrial cancer, liver cancer (including HCC), laryngeal cancer, lung cancer, osteosarcoma, ovary Cancer, pancreatic cancer, prostate cancer, kidney cancer, renal cancer (including RCC), thyroid cancer, acute lymphoblastic leukemia, acute myeloid leukemia, ependymoma, Ewing's sarcoma, glioblastoma, medulloblastoma , neuroblastoma, osteosarcoma, rhabdomyosarcoma, rhabdoid carcinoma, nephroblastoma (Wilm tumor).

In some such embodiments, the compounds detailed herein, or pharmaceutically acceptable salts, prodrugs, metabolites or derivatives thereof, may also be used in combination with additional therapies. Additional therapies 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 transplant , nanotherapy, monoclonal antibody therapy, or a combination of the above.

chemical reaction formula

The compounds of the invention can be synthesized by a variety of methods by those skilled in the art of organic chemistry, and general synthetic schemes for the preparation of the compounds of the invention are described herein. These schemes are illustrative and are not meant to limit the possible methods by which one skilled in the art may prepare the compounds disclosed herein. Different methods of preparing the presently disclosed compounds will be apparent to those skilled in the art. General protocols for the preparation of the compounds of the invention are given in the Examples section listed below. Preparation of homochiral examples can be accomplished by techniques known to those skilled in the art. For example, homochiral compounds can be prepared by chiral phase preparative HPLC separation of racemic products or diastereomers. Alternatively, the example compounds may be prepared by known methods to produce enantiomerically or diastereomerically enriched products.

The reactions and techniques disclosed below in this section are performed in solvents appropriate to the reagents and materials used, and are suitable for the transformations performed. Furthermore, it should be understood that all suggested reaction conditions, including choice of solvent, reaction atmosphere, reaction temperature, experimental duration, and work-up routines, were chosen to be standard for the conditions of this reaction, which should be readily recognized by a person skilled in the art. recognized by technical personnel. Those skilled in the art of organic synthesis also understand that the functional groups present on different parts of the molecule must be compatible with the chosen reagents and reactions. Limitations of substituents compatible with the reaction conditions will be apparent to those skilled in the art, and substitution may be required if incompatible substituents are present. Judgment is sometimes required to modify the order of synthetic steps or to choose one particular route over another to obtain the desired compound of the invention. It will also be understood that the planning of any synthetic route in this field will include judicious selection of protecting groups for protecting the reactive functional groups present in the compounds described herein (Wuts and Greene, Greene's Protective Groups in Organic Synthesis, Fourth Edition , Wiley and Sons (2007)).

The compounds disclosed herein can 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, compounds of the present invention can be prepared using General Reaction Scheme I, after which a deprotection step can be performed to deprotect the protecting groups to obtain the disclosed compounds.

In some embodiments, compounds represented by Formula I and/or Formula (II) are prepared according to the general formula described in Scheme I below. Plan I

Step 1: 3-Bromo-2-methoxypyridin-4-amine

To the ACN (5.0 L, 10.0 V) solution of 2-methoxypyridin-4-amine (B1 is a commercial compound, 500.0g, 4.0 mol, 1.0eq) at 10 °C, NBS (783.1 g was added in one go , 4.4 mol, 1.1 eq), then the mixture was heated to 20 °C and stirred for 1 hour. After the reaction was completed, the reaction mixture was poured into H ₂ O (7.5 L, 15.0 V) and MTBE (5.0 L, 10.0 V), and then the liquids were separated. The aqueous phase was extracted once with MTBE (5.0 L, 10.0 V), the organic phases were combined, washed with 10 wt% NaCl aqueous solution (5.0 L, 10.0 V), dried over anhydrous Na ₂ SO ₄ and concentrated. The crude product was purified by silica gel column chromatography, eluting with n-heptane/EtOAc = 10/1 (2.5 L, 5.0 V) to obtain 3-bromo-2-methoxypyridin-4-amine (706.7 g, content: 93% , yield: 81%) as a brown solid. ¹ H NMR (400 MHz, 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).

Step 2: 3-bromo-5-iodo-2-methoxypyridin-4-amine

To a solution of 3-bromo-2-methoxypyridin-4-amine (706.7 g, content: 93%, 3.3 mol, 1.0 eq) in ACN (7.1 L, 10 V) at 0 °C was added HOAc (19.8 g, 0.33 mol, 0.1 eq) and NIS (1124.9 g, 5.0 mol, 1.5 eq), the mixture was heated to 20 °C and stirred for 2 hours. After the reaction was completed, H ₂ O (35.5 L, 50 V) was slowly added to the reaction mixture. During the addition, solid precipitated. The mixture was stirred for 30 minutes and then filtered. The filter cake was washed with H ₂ O (2 V). The filter cake was collected and dried to obtain 3-bromo-5-iodo-2-methoxypyridin-4-amine (918.7 g, content : 94%, yield: 81%) as a pink solid. ¹ H NMR (400 MHz, DMSO-d6) δ 8.05 (s, 1H), 6.08 (s, 2H), 3.82 (s, 3H).

Step 3: 4-amino-5-bromo-6-methoxynicotinonitrile

At 25 ℃, under _N protection, Zn(CN) ₂ (82.2 g, 0.7 mol, 0.55 eq), Pd ₂ (dba) ₃ (91.6 g, 0.1 mol, 0.1 eq) and dppf (110.9 g, 0.2 mol , 0.2 eq) was added to a solution of 3-bromo-5-iodo-2-methoxypyridin-4-amine (410.0 g, content: 94%, 1.2 mol, 1.0 eq) in DMF (4.1 L, 10 V) . Under _N2 protection, the mixture was heated to 80°C and stirred for 2 hours. After the reaction is completed, the reaction solution is cooled to room temperature, and H ₂ O (20.5 L, 50 V) is slowly added to the mixture. Solids precipitate during the addition. The mixture is filtered, and the filter cake is filtered with H ₂ O (0.8 L, 2 V). Wash. Finally, the filter cake was dissolved with DCM (8.2 L, 20 V), washed with 10 wt% EDTA aqueous solution (4.1 L, 10 V) and 10 wt% NaCl aqueous solution (4.1 L, 10 V), and the organic phase was washed with anhydrous Na ₂ Dry over _SO4 and concentrate. Two batches (410.0 g × 2) of crude product were combined and purified by silica gel column chromatography, eluting with n-heptane/EtOAc = 5/1 to obtain 4-amino-5-bromo-6-methoxynicotinonitrile (342.9 g, Content: 93%, yield: 59%) is a yellow solid. ¹ H NMR (300 MHz, DMSO-d6) δ 8.22 (s, 1H), 6.95 (s, 2H), 3.91 (s, 3H).

Step 4: (E)-4-amino-5-(2-ethoxyvinyl)-6-methoxynicotinonitrile

To 1,4-dioxane (342.9 g, content: 93%, 1.4 mol, 1.0 eq) of 4-amino-5-bromo-6-methoxynicotinonitrile (342.9 g, content: 93%, 1.4 mol, 1.0 eq) at ₂₅ ℃ under N protection 5.1 L, 15 V) solution, add H ₂ O (0.3 L, 1 V), (E)-1-ethoxyvinyl-2-boronic acid pinacol ester (554.6 g, 2.8 mol, 2.0 eq), SPhos (41.1 g, 0.1 mol, 0.075 eq), K ₂ CO ₃ (386.4 g, 2.8 mmol, 2.0 eq) and Pd(OAc) ₂ (9.0 g, 0.04 mol, 0.03 eq). Under _N2 protection, the mixture was heated to 80 °C and stirred for 16 hours. After the reaction was completed, the mixture was cooled to 25 °C, and then EA (6.9 L, 20 V) and H ₂ O (6.9 L, 20 V) were added. After liquid separation, the aqueous phase was extracted with EA (3.5 L, 10 V), and the combined organic phases were washed with 10 wt% NaCl aqueous solution (6.9 L, 20 V), dried over anhydrous Na ₂ SO ₄ and concentrated. The residue was purified by silica gel column chromatography, eluting with n-heptane/EtOAc = 5/1 to obtain (E)-4-amino-5-(2-ethoxyvinyl)-6-methoxynicotinonitrile ( 278.6 g, content: 97%, yield: 89%) as a yellow solid. ¹ H NMR (400 MHz, DMSO-d6) δ 8.03 (s, 1H), 7.15 (d, J = 12.7 Hz, 1H), 6.46 (s, 2H), 5.57 (d, J = 12.7 Hz, 1H), 3.96 – 3.88 (m, 2H), 3.86 (s, 3H), 1.25 (t, J = 7.0 Hz, 3H).

Step 5: 4-methoxy-1H-pyrrolo[3,2-c]pyridine-7-nitrile

Dissolve (E)-4-amino-5-(2-ethoxyvinyl)-6-methoxynicotinonitrile (200.0 g, content: 97%, 885.8 mmol, 1.0 eq) in AcOH (2.0 L, 10.0 V) Heat the solution to 100 ºC and stir for 3 hours. After the reaction was completed, the reaction mixture was concentrated, and MTBE (2.0 L, 10.0 V) was added to the residue. The mixture was stirred for 30 minutes and filtered. The filter cake was collected and dried at 50°C to obtain 4-methoxy-1H-pyrrolo[3,2-c]pyridine-7-nitrile (151.2 g, purity: 95%, content : 93%, yield: 92%) as a light pink solid. ¹ H NMR (400 MHz, DMSO-d6) δ 12.46 (s, 1H), 8.31 (s, 1H), 7.47 (d, J = 13.5 Hz, 1H), 6.64 (s, 1H), 4.05 (s, 3H ).

Step 6: 4-Hydroxy-1H-pyrrolo[3,2-c]pyridine-7-nitrile

To 4-methoxy-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile (150.0 g, content: 93%, 803.8 mmol, 1.0 eq) in ACN (1.5 L, Trimethylsilyl iodide (160.8 g, 803.8 mmol, 1.0 eq) was added to the solution. The mixture was heated to 80 ºC and stirred for 2 hours. After the reaction was completed, the reaction mixture was concentrated, and n-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 to the residue. The mixture was stirred for 30 minutes and filtered, and the filter cake was collected and dried to obtain 4-hydroxy-1H-pyrrolo[3,2-c]pyridine-7-nitrile (120.5 g, purity: 97%, content: 92%, product Ratio: 86%) is a yellow solid. ¹ H NMR (400 MHz, DMSO-d6) δ 12.15 (s, 1H), 11.61 (s, 1H), 7.90 (d, J = 20.6 Hz, 1H), 7.19 – 7.05 (m, 1H), 6.55 (dd , J = 3.0, 2.0 Hz, 1H).

Step 7: 4-Chloro-1H-pyrrolo[3,2-c]pyridine-7-nitrile

To 4-hydroxy-1H-pyrrolo[3,2-c]pyridine-7-nitrile (100.0 g, content: 92%, 576.2 mmol, 1.0 eq) in ACN (0.3 L, 3 V) at 25 °C POCl ₃ (265.0 g, 1728.6 mmol, 3.0 eq) was added to the solution. The mixture was heated to 80 ºC and stirred for 4 hours. After the reaction was completed, the reaction mixture was cooled to 20 °C and slowly poured into H ₂ O (2.0 L, 20 V). The mixture was adjusted to pH 7~8 with 5 wt% _NaHCO3 aqueous solution. The mixture was extracted twice with EA (1.5 L, 15 V), the organic layers were combined, washed with 10 wt% NaCl aqueous solution (1.0 L, 10 V), dried over anhydrous Na ₂ SO ₄ and concentrated. The residue was beaten with n-heptane (0.5 L, 5 V), filtered and dried to obtain 4-chloro-1H-pyrrolo[3,2-c]pyridine-7-nitrile (105.4 g, purity: 93%, content : 79%, yield: 81%) as a brown solid. ¹ H NMR (400 MHz, DMSO-d6) δ 12.97 (s, 1H), 8.53 (s, 1H), 7.79 – 7.64 (m, 1H), 6.81 – 6.68 (m, 1H).

Step 8: 3-bromo-4-chloro-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile

To 4-chloro-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile (50.0 g, content: 79%, 221.0 mmol, 1.0 eq) in DMF (350.0 mL, 7.0 V) at 0 °C To the solution, NBS (39.3 g, 221.0 mmol, 1.0 eq) was added, and the mixture was stirred for 4 hours at 0 °C. After the reaction was completed, the mixture was poured into H ₂ O (1050.0 mL, 35.0 V). During the addition, solid precipitated. The mixture was filtered, and the filter cake was slurried with MTBE (250.0 mL, 5 V) for 2 hours. The mixture was filtered, the filter cake was collected and dried to obtain 3-bromo-4-chloro-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile (50.1 g, purity: 98%, content: 96%, product Ratio: 85%) is a yellow solid. ¹ H NMR (400 MHz, DMSO-d6) δ 13.36 (s, 1H), 8.58 (s, 1H), 7.97 (d, J = 9.0 Hz, 1H).

Step 9: 3-bromo-4-chloro-1-methyl-1H-pyrrolo[3,2-c]pyridine-7-nitrile

To 3-bromo-4-chloro-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile (45.0 g, content: 96%, 169.1 mmol, 1.0 eq) in DMF (450.0 mL, 10.0 V) solution, add K ₂ CO ₃ (46.7 g, 338.2 mmol, 2.0 eq) and methyl iodide (48.0 g, 338.2 mmol, 2.0 eq). The reaction mixture was heated to 25 ºC and stirred for 3 hours. After the reaction was completed, the mixture was poured into H ₂ O (1.8 L, 40.0 V), and a solid precipitated. Filter the mixture, collect the filter cake, and dry to obtain 3-bromo-4-chloro-1-methyl-1H-pyrrolo[3,2-c]pyridine-7-nitrile (42.5 g, purity: 98%, content: 97 %, yield: 90%) is an off-white solid. ¹ H NMR (300 MHz, DMSO-d6) δ 8.56 (d, J = 7.3 Hz, 1H), 7.97 (s, 1H), 4.07 (s, 3H).

Step 10: 4-amino-3-bromo-1-methyl-1H-pyrrolo[3,2-c]pyridine-7-nitrile

To 3-bromo-4-chloro-1-methyl-1H-pyrrolo[3,2-c]pyridine-7-nitrile (40.0 g, content: 97%, 143.6 mmol, 1.0 eq) at 25 °C To the solution of 1,4-dioxane (200.0 mL, 5.0 V), add ammonia water (200.0 mL, 5.0 V). The reaction mixture was heated to 100 ºC and stirred in a closed system for 16 hours. After the reaction was completed, the reaction mixture was concentrated, and the residue was slurried with water (400.0 mL, 10 V) for 30 minutes. The mixture was filtered, and the filter cake was slurried with MTBE (200.0 mL, 5 V) for 2 hours. Filter the mixture, collect the filter cake, and dry to obtain 4-amino-3-bromo-1-methyl-1H-pyrrolo[3,2-c]pyridine-7-nitrile (30.8 g, purity: 98%, content: 97 %, yield: 83%) as a yellow solid.

Step 11: 4-amino-3-bromo-2-iodo-1-methyl-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile

To 4-amino-3-bromo-1-methyl-1H-pyrrolo[3,2-c]pyridine-7-nitrile (25 g, content: 97%, 96.3 mmol, 1.0 eq) at 0 °C To a solution of DMF (250.0 mL, 10.0 V), add p-toluenesulfonic acid monohydrate (1.8 g, 9.6 mmol, 0.1 eq) and NIS (32.1 g, 142.7 mmol, 1.5 eq), and incubate the mixture at 0 ºC Stir the reaction for 3 hours. After the reaction was completed, the mixture was poured into H ₂ O (1.0 L, 40.0 V). Solids precipitated during the pouring process. The mixture was filtered, and the filter cake was slurried with MTBE (250.0 mL, 10 V) for 4 hours. The mixture was filtered, the filter cake was collected and dried to obtain 4-amino-3-bromo-2-iodo-1-methyl-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile (28.0 g, purity: 98 %, content: 92%, yield: 71%) is a white solid. ¹ H NMR (300 MHz, DMSO-d6) δ 8.08 (s, 1H), 6.99 (s, 2H), 3.97 (d, J = 4.6 Hz, 3H).

Step 12: Prepare B15

Step 12 involves combining compound B13 with a compound containing a suitable reactive group The synthon is coupled to form compound B15.

In some embodiments, a suitable reactive group is a boronic acid ester. In some embodiments, a suitable reactive group is pinacol boronate.

Step 13: Preparation of the compound represented by formula (I)

Step 13 involves combining compound B15 with a compound containing a suitable reactive group The synthon is coupled to form the compound represented by formula (1).

In some embodiments, suitable reactive groups are borates or boronic acids.

Other compounds represented by formula (I) and/or formula (II) of the present invention can be prepared by referring to Scheme I.

Detailed implementation

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 various steps described here can be combined. It is also understood that individual batches of compounds can be combined and then used in the next synthetic step.

In the following description of the embodiments, specific embodiments are described. These embodiments are described in sufficient detail to enable those skilled in the art to practice certain embodiments of the disclosure. Logic may be applied to other embodiments and other changes may be made without departing from the scope of the present disclosure. Accordingly, the following description is not intended to limit the scope of the present disclosure, as is specified by the appended claims.

Table 1: Showing some abbreviations of the present invention Abbreviation full name aq. aqueous solution ACN Acetonitrile B ₂ Pin ₂ Pinacol diborate B Benzyl BINAP 1,1'-binaphthyl-2,2'-bisdiphenylphosphine Boc tert-butoxycarbonyl Boc ₂ O Di-tert-butyl dicarbonate ^o C degrees celsius DCM Dichloromethane DIAD Diisopropyl azodicarboxylate DIBAL diisobutylaluminum hydride DIEA diisopropylethylamine DMAP 4-Dimethylaminopyridine DMF N,N-dimethylformamide DMSO DMSO EA Ethyl acetate equiv. Equivalent Et Ethyl FCC flash column chromatography g gram HATU 2-(7-Azobenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate HPLC HPLC LC-MS or LC/MS Liquid Chromatography-Mass Spectrometry Me methyl min minute mL ml mmol millimole MTBE Methyl tert-butyl ether NBS N-bromosuccinimide NIS N-iodosuccinimide NMR NMR NMP N-methylpyrrolidone Pd ₂ (dba) ₃ Tris(dibenzylideneacetone)dipalladium(0) Pd(dppf)Cl ₂ [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride Pd(DtBPF)Cl ₂ [1,1'-Bis(di-tert-butylphosphine)ferrocene]palladium(II) dichloride Pd(OAc) ₂ Palladium(II) acetate Pd(PPh ₃ ) ₄ Tetrakis triphenylphosphine palladium(0) PE Petroleum ether PTSA p-toluenesulfonic acid Prep-TLC preparative thin layer chromatography RuPhos 2-Dicyclohexylphosphine-2',6'-diisopropoxy-1,1'-biphenyl sat. saturated T ₃ P 1-propylphosphonic anhydride TEA Triethylamine TFA Trifluoroacetate TMSI Trimethylsilane iodide THF Tetrahydrofuran TLC thin layer chromatography rt or rt room temperature XPhos-Pd-G2 Chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl) ]Palladium(II)

Example 1

4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2- Methoxy-N-(2,2,2-trifluoroethyl)benzamide (" Compound 1 ")

Step 1: N-(4-(4-amino-3-bromo-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide amine

To 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-dioxaboran-2-yl)phenyl)acrylamide (240 mg, 0.88 mmol) and K ₃ PO ₄ (504 mg, 2.4 mmol) in dioxane/H ₂ O (10 ml/1.0 mL) was added Pd(PPh ₃ ) ₄ (92 mg, 0.08 mmol), and the reaction system was purged with nitrogen three times. The reaction mixture was microwaved in a Biotage Smith reactor at 80 ºC for 1 hour. The reaction mixture was concentrated in vacuo. The residue was washed with EtOAc (20 mL) and H ₂ O (20 ml) to give N-(4-(4-amino-3-bromo-7-cyano-1-methyl-1H-pyrrolo[3, The crude product of 2-c]pyridin-2-yl)phenyl)acrylamide (226 mg) was a yellow solid and was directly used in the next step. MS (ESI): C ₁₈ H ₁₄ BrN ₅ O: 395; m/z ratio 396 [M+1] ⁺ .

Step 2: 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl )-2-Methoxy-N-(2,2,2-trifluoroethyl)benzamide

To 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-dioxaboran-2-yl)-N-(2,2 ,2-Trifluoroethyl)benzamide (136 mg, 0.38 mmol), CsF (114 mg, 0.75 mmol) in DMF (1 ml)/H ₂ O (0.1 ml) solution, add Pd(DtBPF) Cl ₂ (33 mg, 0.05 mmol), and the reaction system was purged with nitrogen three times. The mixture was stirred for 10 minutes at 50°C. After the reaction was completed, the reaction was quenched with water (10 mL) and extracted with EtOAc (10 mL × 3). The organic phases were combined, dried over anhydrous _Na2SO4 , and concentrated _under reduced pressure to obtain a residue. The residue was purified by preparative HPLC ( _NH3 ) to obtain compound 1 (5.78 mg) as a white solid. MS (ESI): C ₂₈ H ₂₃ F ₃ N ₆ O ₃ : 548; m/z ratio 549 [M+H] ⁺ ; ¹ H NMR (400 MHz, DMSO) δ 10.28 (s, 1H), 8.64 ( t, J = 6.4 Hz, 1H), 8.21 (s, 1H), 7.72 – 7.64 (m, 3H), 7.30 (d, J = 8.4 Hz, 2H), 6.97 (s, 1H), 6.89 (d, J = 8.4 Hz, 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).

Example 2

4-(4-Amino-7-cyano-2-(4-(2-fluoroacrylamide)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridine-3- methyl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide ("Compound 2")

Step 1: 2-Fluoro-N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)phenyl)acrylamide

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), and DIPEA (2.36 g, 18.2 mmol) in THF (20 mL) were stirred and reacted at room temperature for 3 hours. After the reaction was completed, the mixture was diluted with water (10 ml) to quench, and the aqueous phase was extracted with EtOAc. The organic layers were combined, dried over anhydrous _Na2SO4 , filtered _and concentrated in vacuo. The residue was purified by FCC (PE/EA = 10/1) to give 2-fluoro-N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2 -(yl)phenyl)acrylamide (1.27 g, yield: 96%) was a white solid. MS (ESI): C ₁₅ H ₁₉ BFNO ₃ 291; m/z ratio 292 [M+H] ⁺ .

Step 2: N-(4-(4-amino-3-bromo-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)-2 -Fluoroacrylamide

To 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-dioxaboran-2-yl)phenyl)acrylamide (154 mg, 0.53 mmol) in DMF/H ₂ O (5 mL/1 mL) solution was added K ₂ CO ₃ (220 mg, 1.59 mmol), Pd(PPh ₃ ) ₄ (58 mg, 0.05 mmol). The reaction mixture was stirred at 100 °C for 2 h under _N protection. After the reaction was completed, the mixture was concentrated, and the residue was purified by column chromatography (DCM:MeOH=10:1) to obtain N-(4-(4-amino-3-bromo-7-cyano-1-methyl- 1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)-2-fluoroacrylamide (200 mg, yield: 91%) was a white solid. MS (ESI): C ₁₈ H ₁₃ BrFN ₅ O: 413; m/z ratio 414 [M+H] ⁺ .

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 N-(4-(4-amino-3-bromo-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)-2-fluoropropene Amide (100 mg, 0.24 mmol) and 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxan-2-yl)-N -To a solution of (2,2,2-trifluoroethyl)benzamide (129 mg, 0.36 mmol) in DMF/H ₂ O (5 mL/1 mL) was added CsF (109 mg, 0.72 mmol) and Pd (DtBPF)Cl ₂ (28 mg, 0.024 mmol). The mixture was stirred and reacted at 50 °C for 2 h under _N protection. After the reaction was completed, the mixture was concentrated, and the residue was purified by preparative HPLC to obtain compound 2 (31.42 mg) as a white solid. MS (ESI): C ₂₈ H ₂₂ F ₄ N ₆ O ₃ : 566; m/z ratio 567 [M+H] ⁺ ; ¹ H NMR (400 MHz, DMSO) δ 10.41 (s, 1H), 8.65 ( t, J = 6.4 Hz, 1H), 8.22 (s, 1H), 7.76 (d, J = 8.8 Hz, 2H), 7.69 (d, J = 7.6 Hz, 1H), 7.33 (d, J = 8.4 Hz, 2H), 6.98 (d, J = 0.8 Hz, 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).

Example 3

N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H- Pyrro[3,2-c]pyridin-2-yl)phenyl]methacrylamide (“Compound 3”)

To 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-dioxaboran-2-yl)phenoxy) To a solution of -4-methylpyrimidine (113 mg, 0.34 mmol) in DMF/H ₂ O (3 mL/0.3 mL) was added Pd(DtBPF)Cl ₂ (7 mg, 0.01 mmol) and CsF (52 mg, 0.34 mmol) ). The mixture was stirred and reacted at 50 °C for 2 h under _N protection. After the reaction was completed, the mixture was concentrated. The residue was purified by preparative HPLC to obtain compound 3 (14.5 mg, yield: 17%) as a white solid. MS (ESI): C ₃₀ H ₂₄ FN ₇ O ₂ 533.57; m/z ratio 534 [M+1] ⁺ ; ¹ H NMR (400 MHz, DMSO) δ 9.94 (s, 1H), 8.47 (d, J = 5.0 Hz, 1H), 8.21 (s, 1H), 7.75 (d, J = 8.5 Hz, 2H), 7.36 (s, 1H), 7.31 (d, J = 8.5 Hz, 2H), 7.24 (dd, J = 11.3, 1.8 Hz, 1H), 7.18 (d, J = 5.0 Hz, 1H), 7.12 (d, J = 8.2 Hz, 1H), 5.79 (s, 1H), 5.54 (s, 1H), 3.80 (s , 3H), 2.41 (s, 3H), 1.95 (s, 3H).

Example 4

N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H- Pyrro[3,2-c]pyridin-2-yl)phenyl]-2-fluoroacrylamide (“Compound 4”)

To N-(4-(4-amino-3-bromo-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-pyridin-2-yl)phenyl)- 2-Fluoroacrylamide (70 mg, 0.17 mmol), 2-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2- To a solution of phenoxy)-4-methylpyrimidine (112 mg, 0.34 mmol) in DMF/H ₂ O (3 mL/0.3 mL), Pd(DtBPPF)Cl ₂ (7 mg, 0.01 mmol) and CsF (52 mg, 0.34 mmol). The mixture was stirred and reacted at 50 °C for 2 h under _N protection. After the reaction was completed, the mixture was concentrated. The residue was purified by preparative HPLC to obtain compound 4 (15 mg, yield: 16%) as a white solid. MS (ESI): C ₂₉ H ₂₁ F ₂ N ₇ O ₂ : 537; m/z ratio 538 [M+1] ⁺ ; ¹ H NMR (400 MHz, DMSO) δ 10.44 (s, 1H), 8.47 ( d, J = 5.0 Hz, 1H), 8.21 (s, 1H), 7.80 (d, J = 8.7 Hz, 2H), 7.35 (d, J = 8.6 Hz, 3H), 7.25 (dd, J = 11.3, 2.0 Hz, 1H), 7.19 (d, J = 5.0 Hz, 1H), 7.14 – 7.11 (m, 1H), 5.79 (d, J = 3.7 Hz, 0.5H), 5.67 (d, J = 3.7 Hz, 0.5H ), 5.46 (dd, J = 15.6, 3.7 Hz, 1H), 3.80 (s, 3H), 2.41 (s, 3H).

Example 5

4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-(methyl-d3)-1H-pyrrolo[3,2-c]pyridin-3-yl )-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide ("Compound 5")

Step 1: 3-bromo-4-chloro-1-(methyl-d3)-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile

₃ -Bromo-4-chloro-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile (1 g, 3.8 mmol) and NaH (273 mg, 11.4 mmol) were dissolved in DMF ( The mixture in 7 mL) was stirred at 0 °C for 0.5 h, then CD ₃ I (1.1 g, 7.6 mmol) was added. The reaction mixture was stirred at room temperature for 2 hours under _N2 protection. After the reaction was completed, H ₂ O (15 mL) was added to quench the reaction, and the reaction mixture was extracted with EtOAc (10 mL × 3). The organic phases were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The residue was purified by FCC (PE/EtOAc = 1:1) to give 3-bromo-4-chloro-1-(methyl-d3)-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile (800 mg, yield: 80%) as a yellow solid. MS (ESI): C ₉ H ₂ D ₃ BrClN ₃ : 273; m/z ratio 274 [M+1] ⁺ .

Step 2: 4-amino-3-bromo-1-(methyl-d3)-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile

3-Bromo-4-chloro-1-(methyl-d3)-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile (800 mg, 2.9 mmol), NH ₃ ·H ₂ O ( A solution of 1,4-dioxane (5 mL) in a sealed tube was heated to 100 °C and stirred for 16 hours. After the reaction was completed, the reactants were concentrated to obtain 4-amino-3-bromo-1-(methyl-d3)-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile crude product (600 mg, collected Ratio: 80%) is a yellow solid, which can be directly put into the next step of reaction. MS (ESI): C ₉ H ₄ D ₃ BrN ₄ : 254; m/z ratio 255 [M+1] ⁺ .

Step 3: 4-amino-3-bromo-2-iodo-1-(methyl-d3)-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile

To 4-amino-3-bromo-1-(methyl-d3)-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile (650 mg, 2.56 mmol) at 25 °C, NIS ( TFA (3 drops) was added to a solution of 632 mg, 2.81 mmol) in DMF (7 mL), and the reaction was stirred for 16 hours. After the reaction was completed, H ₂ O (15 mL) was added to quench the reaction mixture, and the reaction mixture was extracted with EtOAc (10 mL×3). The organic phases were combined, dried over anhydrous Na ₂ SO ₄ and concentrated to obtain 4-amino-3-bromo-2-iodo-1-(methyl-d3)-1H-pyrrolo[3,2-c]pyridine-7 -The crude nitrile (600 mg, yield: 62%) is a yellow solid and can be directly used in the next step of reaction. MS (ESI): C ₉ H ₃ D ₃ BrIN ₄ : 380; m/z ratio 381 [M+1] ⁺ .

Step 4: N-(4-(4-amino-3-bromo-7-cyano-1-(methyl-d3)-1H-pyrrolo[3,2-c]pyridin-2-yl)benzene acrylamide

4-amino-3-bromo-2-iodo-1-(methyl-d3)-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile (600 mg, 1.57 mmol) was prepared under _N2 protection. , N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)phenyl)acrylamide (431 mg, 1.57 mmol), Pd A solution of (PPh ₃ ) ₄ (181 mg, 0.15 mmol) and K ₃ PO ₄ (450 mg, 3.14 mmol) in DMF/H ₂ O (6 mL/2 mL) was reacted in microwave at 80 °C for 1 hour. After the reaction was completed, H ₂ O (10 mL) was added to quench the reaction solution, and the reaction mixture was extracted with EtOAc (5 mL×3). The organic phases were combined, dried over anhydrous Na ₂ SO ₄ and concentrated, and the residue was purified by preparative TLC (PE/EtOAc = 30/70) to obtain N-(4-(4-amino-3-bromo-7-cyano- 1-(Methyl-d3)-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide (400 mg, yield: 64%) was a yellow solid. MS (ESI): C ₁₈ H ₁₁ D ₃ BrN ₅ O: 399; m/z ratio 400 [M+1] ⁺ .

Step 5: 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-(methyl-d3)-1H-pyrrolo[3,2-c]pyridine -3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide

Under the protection of N ₂ , 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-dioxaborane-2- (144 mg, 0.4 mmol), Pd(DtBPF)Cl ₂ (13 mg, 0.02 mmol) and CsF (61 mg, 0.4 mmol) ) in DMF/H ₂ O (3 mL/0.3 mL), stirred for 2 hours at 50 °C. After the reaction was completed, H ₂ O (10 mL) was added to quench the reaction solution, and the reaction mixture was extracted with EtOAc (5 mL×3). The organic phases were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The residue was purified by preparative HPLC to obtain compound 5 (29.64 mg, yield: 27%) as a white solid. MS (ESI): C ₂₈ H ₂₀ D ₃ F ₃ N ₆ O ₃ : 551; m/z ratio 552 [M+1] ⁺ ; ¹ H NMR (400 MHz, DMSO) δ 10.28 (s, 1H), 8.65 (s, 1H), 8.21 (s, 1H), 7.71 – 7.67 (m, 3H), 7.30 (d, J = 8.6 Hz, 2H), 6.98 – 6.88 (m, 2H), 6.41 (d, J = 10.1 Hz, 1H), 6.27 (dd, J = 17.0, 1.9 Hz, 1H), 5.78 (dd, J = 10.0, 2.0 Hz, 1H), 4.08 (dd, J = 9.6, 6.5 Hz, 2H), 3.73 ( s, 3H).

Example 6

N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H- Pyrro[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide ("Compound 6")

Step 1: N-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)phenyl)methacrylamide

To 3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)aniline (3.0 g), methacrylate at 0°C TEA (1.92 g) was added to a solution of chloride (1.45 g) in DCM (20 mL), and the reaction was stirred at 0 °C for 2 hours, and then heated to 20 °C and stirred for 1 hour. After the reaction was completed, the reaction mixture was concentrated. The residue was purified by FCC (60 g silica gel, PE/EtOAc = 80/20) to obtain N-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxy Heteroborane-2-yl)phenyl)methacrylamide (3.1 g) was a white solid. MS (ESI): C ₁₆ H ₂₁ BFNO ₃ 305; m/z ratio 306 [M+1] ⁺ .

Step 2: N-(4-(4-amino-3-bromo-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorobenzene methyl)methacrylamide

Under the protection of _N2 , N-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,5-tetramethyl1,3,2-dioxaborane-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), a solution of Pd(PPh ₃ ) ₄ (861 mg) and K ₃ PO ₄ (6.0 g) in DMF/H ₂ O (50 mL/5 mL) was heated to 70 °C and reacted for 10 hours. After the reaction was completed, H ₂ O (130 mL) was added to quench the reaction solution, and then filtered to obtain N-(4-(4-amino-3-bromo-7-cyano-1-methyl-1H-pyrrolo[ Crude 3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide (2.5 g) was a light brown solid. MS (ESI): C ₁₉ H ₁₅ BrFN ₅ O 427; m/z ratio 428 [M+1] ⁺ .

Step 3: N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl Base-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide

Under the protection of N ₂ , N-(4-(4-amino-3-bromo-7-cyano-1-methyl-1-methyl-1H-pyrrolo[3,2-c]pyridine-2- Pyridin-2-yl)-3-fluorophenylmethacrylamide (1.0 g), 2-(2-fluoro-4-(4,4,4,5,5-tetramethyl-1,3, 3,2-Dioxaboran-2-yl)phenoxy)-4-methylpyrimidine (1.16 g), Pd(DtBPF)Cl ₂ (55 mg) and CsF (1.06 g) in DMF/H ₂ O (10 mL/1 mL) solution, stirred for 6 hours at 50 °C. After the reaction was completed, H ₂ O (50 mL) was added to quench the reaction solution, and then filtered to obtain a light brown solid crude product. The crude product was passed by FCC ( After purification (60 g silica gel, DCM/MeOH=90/10), it was purified again by preparative HPLC to obtain compound 6 (508.63 mg) as a white solid. MS (ESI): C ₃₀ H ₂₃ F ₂ N ₇ O ₂ 551; m /z ratio is 552 [M+1] ⁺ ; ¹ H NMR (400 MHz, DMSO) δ 10.15 (s, 1H), 8.47 (d, J = 5.0 Hz, 1H), 8.23 (s, 1H), 7.79 ( dd, J = 12.4, 1.8 Hz, 1H), 7.54 (dd, J = 8.4, 1.9 Hz, 1H), 7.35 (dd, J = 8.4, 4.7 Hz, 2H), 7.23 (d, J = 11.5 Hz, 1H ), 7.18 (d, J = 5.1 Hz, 1H), 7.10 (d, J = 8.0 Hz, 1H), 5.82 (s, 1H), 5.58 (s, 1H), 3.75 (s, 3H), 2.40 (s , 3H), 1.95 (s, 3H).

Example 7

N-(4-(4-amino-7-cyano-3-(4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H- Pyrro[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide ("Compound 7")

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 Cs ₂ CO ₃ (1.0 g, 3.075 mmol). The reaction mixture was stirred at 100 °C for 4 hours. After the reaction was completed, the reaction mixture was concentrated. The residue was purified by column chromatography (PE:EA=20:1) to obtain 2-(4-bromophenoxy)-5-fluoro-4-methylpyrimidine (400 mg, yield: 69%) as white Oil. MS (ESI): C ₁₁ H ₈ BrFN ₂ O: 282; m/z ratio 283 [M+H] ⁺ .

Step 2: 5-fluoro-4-methyl-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)phenoxy )pyrimidine

To 2-(4-bromophenoxy)-5-fluoro-4-methylpyrimidine (420 mg, 1.5 mmol), B _{Pin 2 (} 568 mg, 2.2 mmol) and AcOK (294 mg) under _N protection , 3.0 mmol) in dioxane/H ₂ O (20 mL), Pd(dppf)Cl ₂ (54 mg, 0.075 mmol) was added. The reaction mixture was stirred at 80°C for 16 hours. After the reaction was completed, the reaction mixture was concentrated. The residue was purified by column chromatography (PE:EA = 20:1) to obtain 5-fluoro-4-methyl-2-(4-(4,4,5,5-tetramethyl-1,3, 2-Dioxaboran-2-yl)phenoxy)pyrimidine (200 mg, yield: 43%) was a white solid. MS (ESI): C ₁₇ H ₂₀ BFN ₂ O ₃ : 330; m/z ratio 331 [M+H] ⁺ .

Step 3: N-(4-(4-amino-7-cyano-3-(4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl Base-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide

To 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- To dioxaboran-2-yl)phenoxy)pyrimidine (89 mg, 0.27 mmol) in DMF/H ₂ O (2.0 mL/0.2 mL) was added CsF (50 mg, 0.33 mmol), Pd(DtBPF )Cl ₂ (11 mg, 0.016 mmol). The reaction mixture was heated to 50°C and stirred for 2 hours. After the reaction was completed, the reaction mixture was concentrated. The residue was purified by column chromatography (DCM:MeOH = 20:1) to obtain compound 7 (10.80 mg, yield: 8%). MS (ESI): C ₃₀ H ₂₃ F ₂ N ₇ O ₂ , 551; m/z ratio 552 [M+H] ⁺ ; ¹ H NMR (400 MHz, DMSO) δ 10.13 (s, 1H), 8.55 ( d, J = 1.2 Hz, 1H), 8.21 (s, 1H), 7.77 (m, 1H), 7.51 (m, 1H), 7.30 (t, J = 8.4 Hz, 3H), 7.20 (d, J = 8.8 Hz, 2H), 5.81 (s, 1H), 5.58 (s, 1H), 3.75 (s, 3H), 2.40 (d, J = 2.8 Hz, 3H), 1.94 (s, 3H).

Example 8

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 8")

Step 1: N-(3-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)phenyl)methacrylamide

To 3-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)aniline (1.0 g, 4 mmol) and To a solution of TEA (0.81 g, 8 mmol) in DCM (10 mL), methacryloyl chloride (0.40 g, 4 mmol) was added, and the reaction mixture was raised to room temperature and stirred for 1 hour. After the reaction was completed, it was concentrated to obtain crude product. The crude product was purified by flash chromatography to obtain N-(3-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)phenyl )methacrylamide (1.1 g). MS (ESI): C ₁₆ H ₂₁ BClNO ₃ : 321; m/z ratio 322 [M+H] ⁺ .

Step 2: N-(4-(4-amino-3-bromo-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorobenzene methyl)methacrylamide

To N-(3-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)phenyl)methacrylene under _N protection Amide (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 ) in DMF/H ₂ O (20.0 mL/4.0 mL), add K ₃ PO ₄ (1.27 g, 6 mmol). The reaction mixture was heated to 80°C and stirred for 12 hours. After the reaction is completed, the reaction mixture is poured into water to quench and filtered, and the filter cake is collected to obtain N-(4-(4-amino-3-bromo-7-cyano-1-methyl-1H-pyrrolo[3, The crude product of 2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide (800 mg) was a light yellow solid and was directly used in the next step of reaction. MS (ESI): C ₁₉ H ₁₅ BrClN ₅ O: 443; m/z ratio 444 [M+H] ⁺ .

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

To 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-dioxabor To a solution of alk-2-yl)phenoxy)pyrimidine (69 mg, 0.22 mmol) in DMF/H ₂ O (5 mL/1 mL), CsF (67 mg, 0.44 mmol) and Pd(DtBPF)Cl ₂ were added (14 mg, 0.022 mmol). The reaction mixture was heated to 50°C and stirred for 2 hours. After the reaction is completed, the reaction mixture is poured into water and filtered, and the filter cake is collected to obtain crude product. The crude product was purified by preparative HPLC to obtain compound 8 (15.56 mg) as a white solid. MS (ESI): C ₃₀ H ₂₄ ClN ₇ O ₂ : 549; m/z ratio 550 [M+H] ⁺ ; ¹ H NMR (400 MHz, DMSO) δ 10.08 (s, 1H), 8.45 (d, J = 5.0 Hz, 1H), 8.21 (s, 1H), 8.03 (d, J = 2.0 Hz, 1H), 7.68 (dd, J = 8.4, 2.0 Hz, 1H), 7.38 (d, J = 8.4 Hz, 1H), 7.29 (d, J = 7.4 Hz, 2H), 7.19 (d, J = 8.8 Hz, 2H), 7.14 (d, J = 5.0 Hz, 1H), 5.82 (s, 1H), 5.57 (s, 1H), 3.69 (s, 3H), 2.39 (s, 3H), 1.94 (s, 3H).

Example 9

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 9")

Step 1: N-(3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)phenyl)methacrylamide amine

To 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline under _N2 protection at 0 ^o C (1.6 g, 6.9 mmol) and TEA (1.0 g, 10.3 mmol) in DCM (20 mL), methacrylyl chloride (789.0 mg, 7.5 mmol) was added dropwise. The reaction mixture was heated to 25°C and stirred for 3 hours. After the reaction was completed, water (200 ml) was added to the reaction mixture to quench the reaction, and extracted with DCM (10 ml x 3). The organic phases were combined, dried over anhydrous Na ₂ SO ₄ and concentrated, and the residue was purified through a flash chromatography column (DCM:PE = 0:100~100:0) to obtain N-(3-methyl-4-(4, 4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methacrylamide (1.7 g, yield: 93%) is a yellow solid . MS (ESI): C ₁₇ H ₂₄ BNO ₃ : 301; m/z ratio 302 [M+H] ⁺ .

Step 2: N-(4-(4-amino-3-bromo-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methyl Phenyl)methacrylamide

To 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-dioxaboran-2-yl)phenyl)methacrylamide (479.5 mg, 1.6 mmol ) in DMF/H ₂ O (5 mL/0.5 mL), add Pd(PPh ₃ ) ₄ (153.7 mg, 0.13 mmol) and K ₃ PO ₄ (844.5 mg, 4.0 mmol). The reaction mixture was stirred in the microwave at 80 ^° C for 70 minutes under _N2 protection. After the reaction was completed, water (50 ml) was added to quench the reaction mixture, and extracted with EA (20 ml x 3). The organic phases were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The residue was purified by flash column chromatography (MeOH:DCM = 0:100~5:95) to obtain N-(4-(4-amino-3-bromo-7-cyano-1-methyl-1H-pyrrole) And[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide (250 mg, yield: 45%) was a yellow solid. MS (ESI): C ₂₀ H ₁₈ BrN ₅ O: 423; m/z ratio 424 [M+H] ⁺ .

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 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-dioxa To a solution of borane-2-yl)phenoxy)pyrimidine (183.9 mg, 0.59 mmol) in DMF/H ₂ O (2 mL/0.2 mL) was added Pd(dtbpf)Cl ₂ (38.1 mg, 0.059 mmol) and CsF (178.9 mg, 1.18 mmol). The reaction mixture was heated to 50°C and stirred for 2 hours. After the reaction was completed, water (20 ml) was added to quench the reaction and extracted with EA (10 mL x 3). The organic phases were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The residue was purified by preparative HPLC to obtain compound 9 (22.5 mg) as a white solid. MS (ESI): C ₃₁ H ₂₇ N ₇ O ₂ : 529; m/z ratio 530 [M+H] ⁺ ; ¹ H NMR (400 MHz, DMSO) δ 9.86 (s, 1H), 8.45 (d, J = 5.2 Hz, 1H), 8.37 (s, 1H), 7.65 (d, J = 1.6 Hz, 1H), 7.60 (dd, J = 8.4, 2.0 Hz, 1H), 7.30 – 7.23 (m, 3H), 7.18 (d, J = 8.8 Hz, 3H), 7.15 (d, J = 5.2 Hz, 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).

Example 10

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 10")

To 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-dioxaborane- To a solution of 2-yl)phenoxy)-1-methyl-1H-pyrazole (89 mg, 0.29 mmol) in dioxane/H ₂ O (8 ml/2 mL), CsF (90 mg, 0.57 mmol) and Pd(DtBPF)Cl ₂ (24 mg, 0.02 mmol). The reaction mixture was heated to 50°C and stirred for 1 hour. After the reaction was completed, the reaction was concentrated, and the residue was purified by silica gel chromatography (DCM/MeOH=10/1) to obtain a crude product. The crude product was further purified by preparative HPLC to obtain compound 10 (27.91 mg, yield: 34%) as a white solid. MS (ESI): C ₂₅ H ₂₀ FN ₉ O: 539; m/z ratio 540 [M+1] ⁺ ; ¹ H NMR (400 MHz, DMSO) δ 10.13 (s, 1H), 8.21 (s, 1H ), 7.76 (dd, J = 12.4, 1.8 Hz, 1H), 7.63 (d, J = 2.4 Hz, 1H), 7.51 (dd, J = 8.4, 2.0 Hz, 1H), 7.29 (t, J = 8.4 Hz , 1H), 7.16 (t, J = 8.6 Hz, 2H), 6.99 (d, J = 8.0 Hz, 1H), 5.88 – 5.80 (m, 2H), 5.58 (s, 1H), 3.74 (s, 3H) , 3.72 (s, 3H), 1.95 (s, 3H).

Example 11

N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H- Pyrro[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide ("Compound 11")

To N-( _4- (4-amino-3-bromo-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-3- Methyl)methacrylamide (190.0 mg, 0.45 mmol) and 2-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxabor) To a solution of alk-2-yl)phenoxy)-4-methylpyrimidine (147.9 mg, 0.45 mmol) in DMF/H ₂ O (2 mL/0.2 mL), Pd(dtbpf)Cl ₂ (29.1 mg, 0.045 mmol) and CsF (136.1 mg, 0.90 mmol). The reaction mixture was heated to 50 °C and stirred for 2 hours. After the reaction was completed, water (20 ml) was added to quench the reaction and extracted with EA (10 mL x 3). The organic phases were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The residue was purified by preparative HPLC to obtain compound 11 (26.0 mg) as a white solid. MS (ESI): C ₃₁ H ₂₆ FN ₇ O ₂ : 547; m/z ratio 548 [M+H] ⁺ ; ¹ H NMR (400 MHz, DMSO) δ 9.89 (s, 1H), 8.46 (d, J = 5.2 Hz, 1H), 8.39 (s, 1H), 7.67 (s, 1H), 7.65 – 7.58 (m, 1H), 7.35 (t, J = 8.4 Hz, 1H), 7.27 (d, J = 8.4 Hz, 1H), 7.21 (dd, J = 11.6, 2.0 Hz, 1H), 7.18 (d, J = 5.2 Hz, 1H), 7.07 (d, J = 10.0 Hz, 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).

Example 12

N-(4-(4-amino-7-cyano-1-methyl-3-(4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)-1H- Pyrro[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide ("Compound 12")

To 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-dioxaboron) To a solution of alk-2-yl)phenoxy)-1H-pyrazole (98 mg, 0.22 mmol) in DMF/H ₂ O (10 mL/1.0 mL), CsF (71 mg, 0.44 mmol) and Pd ( DtBPF)Cl ₂ (14 g, 0.022 mmol), the reaction mixture was heated to 50 °C and stirred for 2 hours. After the reaction was completed, the reaction mixture was concentrated. The residue was purified by preparative HPLC to obtain compound 12 (12.31 mg) as a white solid. MS (ESI): C ₂₉ H ₂₄ ClN ₇ O ₂ : 537; m/z ratio 538 [M+H] ⁺ ; ¹ H NMR (400 MHz, DMSO) δ 10.08 (s, 1H), 8.20 (s, 1H), 8.01 (d, J = 2.0 Hz, 1H), 7.64 (d, J = 2.3 Hz, 2H), 7.33 (d, J = 8.4 Hz, 1H), 7.20 (d, J = 6.9 Hz, 2H) , 7.02 (d, J = 8.8 Hz, 2H), 5.88 (d, J = 2.3 Hz, 1H), 5.82 (s, 1H), 5.58 (s, 1H), 3.74 (s, 3H), 3.68 (s, 3H), 1.94 (s, 3H).

Example 13

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 13")

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/THF (3 ml/18 mL) under _N protection was added Magnesium iodide (5.5 mL, 33.0 mmol). The reaction mixture was stirred at 25°C for 12 hours. After the reaction was completed, H ₂ O was added to quench the reaction, and the mixture was extracted with EA. The organic phases were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The residue was purified by silica gel chromatography (PE/EA=20/1) to obtain 2,5-dichloro-4-methylpyrimidine (1.1 g, yield: 41%) as a light yellow oil. MS (ESI): C ₅ H ₄ Cl ₂ N ₂ : 162; m/z ratio 163 [M+1] ⁺ .

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 Cs ₂ CO ₃ (4.43 g, 13.6 mmol) in DMF (25 ml) was added 4-bromo-2-fluorophenol (1.42 g, 7.5 mmol). The reaction mixture was heated to 100 °C and stirred for 12 hours. After the reaction was completed, it was purified by silica gel chromatography (PE/EA=20/1) to obtain 2-(4-bromo-2-fluorophenoxy)-5-chloro-4-methylpyrimidine (1.3 g, collected Rate: 61%) is a yellow oily substance. MS (ESI): C ₁₁ H ₇ BrClFN ₂ O 316; m/z ratio 317 [M+1] ⁺ .

Step 3: 5-chloro-2-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)phenoxy) -4-methylpyrimidine

To 2-(4-bromo-2-fluorophenoxy)-5-chloro-4-methylpyrimidine (1.3 g, 4.1 mmol), B ₂ Pin ₂ (1.57 g, 6.2 mmol) and KOAc (806 mg, To a solution of 8.2 mmol) in dioxane (25 mL) was added Pd(dppf)Cl ₂ (343 mg, 0.42 mmol) and purged with nitrogen three times. The reaction mixture was heated to 80 °C and stirred for 16 hours. After the reaction, the residue was purified by silica gel chromatography (PE/EA=20/1) to obtain 5-chloro-2-(2-fluoro-4-(4,4,5,5-tetramethyl-1) ,3,2-Dioxaboran-2-yl)phenoxy)-4-methylpyrimidine (1.25 g, yield: 84%) is a light green solid. MS (ESI): C ₁₇ H ₁₉ BClFN ₂ O ₃ : 364; m/z ratio 365 [M+1] ⁺ .

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 5-chloro-2-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)phenoxy under _N protection methyl)-4-methylpyrimidine (150 mg, 0.40 mmol), N-(4-(4-amino-3-bromo-7-cyano-1-methyl-1H-pyrrolo[3,2-c To a solution of ]pyridin-2-yl)phenyl)acrylamide (80 mg, 0.20 mmol) and CsF (61 mg, 0.40 mmol) in DMF/H ₂ O (5 ml/0.5 mL) was added Pd(DtBPF)Cl ₂ (13 mg, 0.02 mmol). The reaction mixture was heated to 50°C and stirred for 2 hours. After the reaction, the residue was purified by silica gel chromatography (DCM/MeOH=10/1) to obtain the crude product, which was further purified by preparative HPLC to obtain compound 13 (23.36 mg, yield: 21%) as a white solid. MS (ESI): C ₂₉ H ₂₁ ClFN ₇ O ₂ : 553; m/z ratio 554 [M+1] ⁺ ; ¹ H NMR (400 MHz, DMSO) δ 10.34 (s, 1H), 8.63 (s, 1H), 8.42 (s, 1H), 7.76-7.74 (d, J = 8.0 Hz, 2H), 7.42-7.38 (t, J = 8.0 Hz, 1H), 7.33-7.31 (d, J = 8.0 Hz, 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).

Examples of compounds of the invention include the compounds listed in Table 2 and exemplified herein, or pharmaceutically acceptable salts, prodrugs, solvates, hydrates, tautomers and isomers thereof. Some of these compounds can be prepared according to similar methods of Examples 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13; some of these compounds can also be prepared with reference to the Examples above examples or combinations thereof.

Table 2: Compound serial number Name ¹ H NMR LC-MS [M+H] ⁺ 14 N-(4-(4-amino-7-cyano-3-(4-(cyclohexyloxy)-3-fluorophenyl)-1-methyl-1H-pyrrolo[3,2-c] Pyridin-2-yl)phenyl)acrylamide; ¹ H NMR (400 MHz, DMSO-d6) δ 10.30 (s, 1H), 8.35 (s, 1H), 7.71 (d, J = 8.6 Hz, 2H), 7.27 (d, J = 8.6 Hz, 2H), 7.18 (t, J = 8.8 Hz, 1H), 7.07 (dd, J = 12.0, 2.1 Hz, 1H), 6.99 - 6.91 (m, 1H), 6.43 (dd, J = 17.0, 10.1 Hz, 1H), 6.27 (dd, J = 17.0, 2.0 Hz, 1H), 5.78 (dd, J = 10.1, 2.0 Hz, 1H), 4.36 (dt, J = 8.9, 5.0 Hz, 1H), 3.83 (s, 3H), 2.01 - 1.83 (m, 2H), 1.70 (dt, J = 7.3, 4.3 Hz, 2H), 1.62 - 1.17 (m, 6H). 510 15 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; ¹ H NMR (400 MHz, DMSO) δ 10.29 (s, 1H), 8.40 (d, J = 5.2 Hz, 1H), 8.20 (s, 1H), 7.72 (m, 2H), 7.35 (d, J = 8.4 Hz, 2H), 7.15 (d, J = 8.0 Hz, 1H), 7.09 (d, J = 5.2 Hz, 1H), 6.99 (d, J = 1.6 Hz, 1H), 6.86 (m, 1H), 6.49 - 6.40 (m, 1H), 6.29 (m, 1H), 5.78 (m, 1H), 3.81 (s, 3H), 3.55 (s, 3H), 2.38 (s, 3H). 532 16 2-(4-Acrylamidephenyl)-4-amino-3-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl Base-1H-pyrrolo[3,2-c]pyridine-7-carboxamide; ¹ H NMR (400 MHz, MeOD) δ 8.34 (d, J = 4.8 Hz, 1H), 7.93 (s, 1H), 7.68 (d, J = 8.4 Hz, 2H), 7.30 (d, J = 8.4 Hz, 2H), 7.14 - 7.06 (m, 2H), 6.93 (d, J = 8.8 Hz, 2H), 6.46 - 6.33 (m, 2H), 5.78 (m, 1H), 3.66 (s, 3H), 3.56 (s , 3H), 2.46 (s, 3H). 550 17 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; ¹ H NMR (400 MHz, MeOD) δ 8.39 (d, J = 4.8 Hz, 1H), 8.05 (s, 1H), 7.62 (d, J = 8.8 Hz, 2H), 7.39 (d, J = 8.8 Hz, 2H), 7.25 (d, J = 8.0 Hz, 1H), 7.15 - 7.07 (m, 2H), 7.07 - 6.98 (m, 1H), 6.49 - 6.31 (m, 2H), 5.77 (m, 1H), 3.63 (s, 3H), 2.49 (s, 3H). 518 18 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclopropyl-2 -Methoxybenzamide; ¹ H NMR (400 MHz, DMSO) δ 12.45 (s, 1H), 10.22 (s, 1H), 8.20 - 8.09 (m, 2H), 7.68 (d, J = 7.8 Hz, 1H), 7.60 (d, J = 8.6 Hz, 2H), 7.33 (d, J = 8.6 Hz, 2H), 7.07 (s, 1H), 6.96 (d, J = 7.8 Hz, 1H), 6.46 - 6.37 (m, 1H), 6.25 (dd , J = 17.0, 1.6 Hz, 1H), 5.76 (dd, J = 10.1, 1.7 Hz, 3H), 3.76 (s, 3H), 2.84 (d, J = 3.9 Hz, 1H), 0.76 - 0.65 (m, 2H), 0.56 (dd, J = 6.5, 3.8 Hz, 2H). 493 19 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-(2-hydroxyethyl)-1H-pyrrolo[3,2-c]pyridine-3- base)-N-cyclobutyl-2-methoxybenzamide; ¹ H NMR (400 MHz, DMSO) δ 10.26 (s, 1H), 8.24 (d, J = 7.8 Hz, 1H), 8.19 (s, 1H), 7.68 (d, J = 8.6 Hz, 2H), 7.57 ( d, J = 7.8 Hz, 1H), 7.34 (d, J = 8.5 Hz, 2H), 6.95-6.83 (m, 2H), 6.43 (dd, J = 17.0, 10.0 Hz, 1H), 6.27 (dd, J = 17.0, 2.0 Hz, 1H), 5.77 (dd, J = 10.1, 1.9 Hz, 1H), 4.90 (t, J = 5.2 Hz, 1H), 4.44-4.24 (m, 3H), 3.71 (s, 3H) , 3.64-3.51 (m, 2H), 2.24-2.15 (m, 2H), 2.04-1.91 (m, 2H), 1.74-1.56 (m, 2H). 551 20 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-(2-methoxyethyl)-1H-pyrrolo[3,2-c]pyridine- 3-yl)-N-cyclobutyl-2-methoxybenzamide; ¹ H NMR (400 MHz, DMSO) δ 10.28 (s, 1H), 8.24 (d, J = 8.0 Hz, 2H), 8.21 (s, 1H), 7.69 (d, J = 8.4 Hz, 2H), 7.56 ( d, J = 8.0 Hz, 1H), 7.33 (d, J = 8.4 Hz, 2H), 6.94 (d, J = 1.2 Hz, 2H), 6.87 (m, 1H), 6.43 (m, 1H), 6.27 ( m, 1H), 5.78 (m, 1H), 4.38 (m, 3H), 3.72 (s, 3H), 3.51 (t, J = 5.6 Hz, 2H), 3.07 (s, 3H), 2.19 (m, 2H ), 2.04 - 1.92 (m, 2H), 1.69 - 1.60 (m, 2H). 565 twenty one 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N- Isobutyl-2-methoxybenzamide; ¹ H NMR (400 MHz, DMSO) δ 10.31 (s, 1H), 8.21 (s, 1H), 8.11 (t, J = 5.6 Hz, 1H), 7.67 (m, 3H), 7.30 (d, J = 8.4 Hz, 2H), 6.95 (s, 1H), 6.88 (d, J = 8.0 Hz, 1H), 6.43 (m, 1H), 6.26 (m, 1H), 5.77 (d, J = 10.4 Hz, 1H), 3.80 (s, 3H), 3.72 (s, 3H), 3.08 (t, J = 6.4 Hz, 2H), 1.80 (m, 1H), 0.88 (d, J = 6.4 Hz, 6H). 523 twenty two 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N- cyclobutylbenzamide; ¹ H NMR (400 MHz, DMSO) δ 10.26 (s, 1H), 8.61 (d, J = 7.5 Hz, 1H), 8.20 (s, 1H), 7.79 (d, J = 8.1 Hz, 2H), 7.67 ( d, J = 8.5 Hz, 2H), 7.28 (dd, J = 19.5, 8.3 Hz, 4H), 6.42 (dd, J = 17.0, 10.1 Hz, 1H), 6.26 (dd, J = 16.9, 1.8 Hz, 1H ), 5.93 (s, 1H), 5.77 (d, J = 12.0 Hz, 1H), 4.39 (dd, J = 15.8, 8.0 Hz, 1H), 3.81 (s, 3H), 2.19 (d, J = 7.5 Hz , 2H), 2.03 (dd, J = 20.7, 9.0 Hz, 2H), 1.72 - 1.61 (m, 2H). 491 twenty three 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N- cyclobutyl-2-methoxybenzamide; ¹ H NMR (400 MHz, DMSO) δ 10.28 (s, 1H), 8.30 - 8.18 (m, 2H), 7.69 (d, J = 8.5 Hz, 2H), 7.59 (d, J = 7.8 Hz, 1H), 7.30 (d, J = 8.5 Hz, 2H), 6.93 (s, 1H), 6.87 (d, J = 7.9 Hz, 1H), 6.43 (dd, J = 16.9, 10.0 Hz, 1H), 6.32 - 6.20 (m , 1H), 5.82 - 5.73 (m, 1H), 4.37 (dd, J = 16.5, 8.2 Hz, 1H), 3.80 (s,3H), 3.72 (s, 3H), 2.23 (dd, J = 29.0, 25.5 Hz,2H), 1.98 (dd, J = 14.7, 6.4 Hz, 2H), 1.65 (m, 2H). 521 twenty four N-(4-(4-amino-7-cyano-1-methyl-3-(4-(pyrimidin-2-yloxy)phenyl)-1H-pyrrolo[3,2-c]pyridine -2-yl)phenyl)acrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.28 (s, 1H), 8.66 (d, J = 4.8 Hz, 2H), 8.19 (s, 1H), 7.71 (d, J = 8.5 Hz, 2H), 7.34 - 7.26 (m, 5H), 7.22 (d, J = 8.5 Hz, 2H), 6.43 (dd, J = 16.9, 10.1 Hz, 1H), 6.27 (d, J = 16.9 Hz, 1H), 5.98 (s, 1H ), 5.80 - 5.75 (m, 1H), 3.80 (s, 3H). 488 25 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; ¹ H NMR (400 MHz, DMSO) δ 10.30 (br s, 1H), 8.61 (d, J = 4.8 Hz, 2H), 8.20 (s, 1H), 7.73 (d, J = 8.5 Hz, 2H), 7.35 (d, J = 8.5 Hz, 2H), 7.23 (t, J = 4.8 Hz, 1H), 7.19 (d, J = 8.1 Hz, 1H), 7.00 (d, J = 1.6 Hz, 1H), 6.88 (dd , J = 8.0, 1.7 Hz, 1H), 6.48 - 6.39 (m, 1H), 6.32 - 6.24 (m, 1H), 5.78 (dd, J = 10.1, 1.9 Hz, 1H), 3.80 (s, 3H), 3.55 (s, 3H). 518 26 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; ¹ H NMR (400 MHz, DMSO) δ 10.28 (s, 1H), 8.46 (d, J = 4.8 Hz, 1H), 8.19 (s, 1H), 7.70 (d, J = 8.4 Hz, 2H), 7.32 - 7.29 (m, 4H), 7.17 (m, 3H), 6.43 (m, 1H), 6.27 (m, 1H), 5.78 (m, 1H), 3.81 (s, 3H), 2.40 (s, 3H). 502 27 4-(4-Amino-7-cyano-2-(4-(2-fluoroacrylamide)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridine-3- base)-N-cyclobutylbenzamide; ¹ H NMR (400 MHz, DMSO) δ 10.41 (s, 1H), 8.63 (d, J = 7.6 Hz, 1H), 8.21 (s, 1H), 7.77 (m, 4H), 7.34 - 7.27 (m, 4H ), 6.27 - 5.32 (m, 4H), 4.39 (m, 1H), 3.81 (s, 3H), 2.24 - 2.15 (m, 2H), 2.09 - 1.99 (m, 2H), 1.66 (m, 2H). 509 28 4-(4-Amino-7-cyano-2-(4-(2-fluoroacrylamide)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridine-3- base)-N-cyclopropyl-2-methoxybenzamide; ¹ H NMR (400 MHz, DMSO) δ 10.41 (s, 1H), 8.21 (s, 1H), 8.07 (d, J = 4.0 Hz, 1H), 7.76 (d, J = 8.4 Hz, 2H), 7.58 ( d, J = 8.0 Hz, 1H), 7.33 (d, J = 8.4 Hz, 2H), 6.95 - 6.83 (m, 2H), 6.58 - 5.35 (m, 4H), 3.80 (s, 3H), 3.69 (s , 3H), 2.80 (m, 1H), 0.73 - 0.60 (m, 2H), 0.58 - 0.45 (m, 2H). 525 29 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N- Cyclopropyl-2-methoxybenzamide; ¹ H NMR (400 MHz, DMSO) δ 10.28 (s, 1H), 8.21 (s, 1H), 8.06 (d, J = 4.4 Hz, 1H), 7.69 (d, J = 8.4 Hz, 2H), 7.58 ( d, J = 7.6 Hz, 1H), 7.30 (d, J = 8.4 Hz, 2H), 6.92 (s, 1H), 6.87 (d, J = 7.6 Hz, 1H), 6.43 (m, 1H), 6.30 - 6.24 (m, 1H), 6.05 (s, 1H), 5.80 - 5.74 (m, 1H), 3.80 (s, 3H), 3.69 (s, 3H), 2.80 (m, 1H), 0.67 (d, J = 5.2 Hz, 2H), 0.52 (d, J = 2.8 Hz, 2H). 507 30 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N- (2,2,2-trifluoroethyl)benzamide; ¹ H NMR (400 MHz, DMSO) δ 10.27 (s, 1H), 9.10 (t, J = 6.0 Hz, 1H), 8.21 (s, 1H), 7.85 (d, J = 8.0 Hz, 2H), 7.67 ( d, J = 8.4 Hz, 2H), 7.34 (d, J = 8.4 Hz, 2H), 7.26 (d, J = 8.8 Hz, 2H), 6.42 (m, 1H), 6.31 - 5.83 (m, 1H), 5.79 - 5.75 (m, 1H), 4.06 (m, 2H), 3.81 (s, 3H). 519 31 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N- Ethyl-2-methoxybenzamide; ¹ H NMR (400 MHz, DMSO) δ 10.28 (s, 1H), 8.21 (s, 1H), 8.15 (t, J = 5.6 Hz, 1H), 7.69 (m, 3H), 7.30 (d, J = 8.4 Hz, 2H), 6.94 (d, J = 0.8 Hz, 1H), 6.88 (m, 1H), 6.43 (m, 1H), 6.34 - 5.82 (m, 3H), 5.78 (m, 1H), 3.81 (s , 3H), 3.72 (s, 3H), 3.27 (m, 2H), 1.09 (t, J = 7.2 Hz, 3H). 495 32 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N- Isopropyl-2-methoxybenzamide; ¹ H NMR (400 MHz, DMSO) δ 10.28 (s, 1H), 8.21 (s, 1H), 7.89 (d, J = 7.6 Hz, 1H), 7.69 (d, J = 8.8 Hz, 2H), 7.63 ( d, J = 7.6 Hz, 1H), 7.30 (d, J = 8.8 Hz, 2H), 6.93 (s, 1H), 6.87 (d, J = 7.6 Hz, 1H), 6.43 (m, 1H), 6.27 ( m, 3H), 5.78 (m, 1H), 4.04 (m, 1H), 3.80 (s, 3H), 3.72 (s, 3H), 1.14 (d, J = 6.8 Hz, 6H). 509 33 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N- Cyclopentyl-2-methoxybenzamide; ¹ H NMR (400 MHz, DMSO) δ 10.27 (s, 1H), 8.21 (s, 1H), 7.99 (d, J = 7.2 Hz, 1H), 7.69 (d, J = 8.4 Hz, 2H), 7.61 ( d, J = 7.6 Hz, 1H), 7.30 (d, J = 8.4 Hz, 2H), 6.93 (s, 1H), 6.87 (d, J = 8.4 Hz, 1H), 6.43 (m, 1H), 6.27 ( d, J = 16.8 Hz, 1H), 5.78 (d, J = 11.6 Hz, 1H), 4.18 (m, 1H), 3.80 (s, 3H), 3.71 (s, 3H), 1.84 (m, 2H), 1.65 (m, 2H), 1.57 - 1.43 (m, 4H). 535 34 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N- Cyclohexyl-2-methoxybenzamide; ¹ H NMR (400 MHz, DMSO) δ 10.27 (s, 1H), 8.21 (s, 1H), 7.93 (d, J = 8.0 Hz, 1H), 7.69 (d, J = 8.4 Hz, 2H), 7.64 ( d, J = 8.0 Hz, 1H), 7.30 (d, J = 8.4 Hz, 2H), 6.94 (s, 1H), 6.87 (d, J = 8.0 Hz, 1H), 6.43 (m, 1H), 6.27 ( m, 3H), 5.78 (d, J = 11.6 Hz, 1H), 3.80 (s, 3H), 3.72 (s, 4H), 1.84 - 1.54 (m, 5H), 1.36 - 1.16 (m, 5H). 549 35 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N- ((1-cyanocyclopropyl)methyl)-2-methoxybenzamide; ¹ H NMR (400 MHz, DMSO) δ 10.28 (s, 1H), 8.49 (t, J = 6.4 Hz, 1H), 8.21 (s, 1H), 7.68 (m, 3H), 7.30 (d, J = 8.4 Hz, 2H), 6.96 (s, 1H), 6.92 - 6.87 (m, 1H), 6.43 (m, 1H), 6.27 (m, 1H), 6.24 - 5.80 (m, 2H), 5.78 (m, 1H) , 3.81 (s, 3H), 3.74 (s, 3H), 3.44 (d, J = 6.0 Hz, 2H), 1.18 (s, 2H), 1.11 (s, 2H). 546 36 4-(2-(4-Acrylamide-2-methoxyphenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridine-3 -yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; ¹ H NMR (400 MHz, DMSO) δ 10.31 (s, 1H), 8.62 (t, J = 6.4 Hz, 1H), 8.20 (s, 1H), 7.69 (d, J = 8.0 Hz, 1H), 7.61 ( s, 1H), 7.19-7.16(m, 1H), 7.04 (d, J = 8.0 Hz, 1H), 6.90 (m, 2H), 6.43 (m, 1H), 6.30 - 6.25 (m, 1H), 5.79 (m, 1H), 4.12 - 4.03 (m, 2H), 3.73 (m, 6H), 3.69 (s, 3H). 579 37 4-(2-(4-Acrylamide-2-fluorophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) -2-Methoxy-N-(2,2,2-trifluoroethyl)benzamide; ¹ H NMR (400 MHz, MeOD) δ 8.14 (s, 1H), 7.89 - 7.84 (m, 1H), 7.82 - 7.74 (m, 1H), 7.38 - 7.28 (m, 1H), 7.26 - 7.15 (m, 1H), 7.10 - 6.89 (m, 2H), 6.44 - 6.37 (m, 2H), 5.81 (m, 1H), 4.14 - 4.07 (m, 2H), 3.88 (s, 3H), 3.82 (s, 3H) . 567 38 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; ¹ H NMR (400 MHz, MeOD) δ 8.15 (s, 1H), 7.95 - 7.83 (m, 1H), 7.82 - 7.67 (m, 1H), 7.50 - 7.40 (m, 1H), 7.29 - 7.18 (m, 1H), 7.12 - 6.84 (m, 2H), 5.82 - 5.66 (m, 1H), 5.42 - 5.24 (m, 1H), 4.11 (q, J = 9.3 Hz, 2H), 3.88 (s, 3H), 3.82 (s, 3H). 585 39 4-(2-(4-Acrylamide-2-methoxyphenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridine-3 -base)-N-cyclopropyl-2-methoxybenzamide; ¹ H NMR (400 MHz, DMSO) δ 10.31 (s, 1H), 8.19 (s, 1H), 8.04 (d, J = 4.4 Hz, 1H), 7.59 - 7.57 (m, 2H), 7.18 - 7.16 (m , 1H), 7.04 (d, J = 8.0 Hz, 1H), 6.85 (s, 2H), 6.46-6.40 (m, 1H), 6.30 - 6.25 (m, 1H), 5.80 - 5.77 (m, 1H), 3.74 (s, 3H), 3.67 (s, 6H), 2.84 - 2.77 (m, 1H), 0.69-0.63 (m, 2H), 0.53-0.49 (m, 2H). 537 40 4-(2-(4-Acrylamide-2-fluorophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) -N-cyclopropyl-2-methoxybenzamide; ¹ H NMR (400 MHz, DMSO) δ 10.53 (s, 1H), 8.23 (s, 1H), 8.06 (d, J = 4.2 Hz, 1H), 7.78 (d, J = 11.1 Hz, 1H), 7.58 ( d, J = 7.8 Hz, 1H), 7.33 (dd, 2H), 6.92 - 6.83 (m, 2H), 6.61 - 5.88 (m, 4H), 5.82 (dd, J = 10.1, 1.7 Hz, 1H), 3.75 (s, 3H), 3.70 (s, 3H), 2.84 - 2.76 (m, 1H), 0.69 - 0.64 (m, 2H), 0.54 - 0.49 (m, 2H). 525 41 4-(4-Amino-7-cyano-2-(4-(2-fluoroacrylamide)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridine-3- base)-N-isopropyl-2-methoxybenzamide; ¹ H NMR (400 MHz, DMSO) δ 10.41 (s, 1H), 8.21 (s, 1H), 7.89 (d, J = 7.7 Hz, 1H), 7.76 (d, J = 8.5 Hz, 2H), 7.62 ( d, J = 7.8 Hz, 1H), 7.33 (d, J = 8.5 Hz, 2H), 6.94 (s, 1H), 6.87 (d, J = 7.9 Hz, 1H), 5.78 (d, J = 3.6 Hz, 0.5H), 5.66 (d, J = 3.7 Hz, 0.5H), 5.45 (dd, J = 15.6, 3.6 Hz, 1H), 4.09 - 3.99 (m, 1H), 3.80 (s, 3H), 3.72 (s , 3H) 1.14 (d, J = 6.5 Hz, 6H). 527 42 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; ¹ H NMR (400 MHz, DMSO) δ 10.29 (s, 1H), 8.95 (m, 1H), 8.22 (s, 1H), 7.71 (d, J = 8.6 Hz, 2H), 7.59 (m, 1H), 7.28 (d, J = 8.6 Hz, 2H), 7.19 - 7.09 (m, 2H), 6.43 (m, 1H), 6.27 (m, 1H), 5.78 (m, 1H), 4.06 (m, 2H), 3.79 (s, 3H). 43 N-(4-(4-amino-7-cyano-3-(4-(cyclopentyloxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2- Base) benzene) acrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.26 (s, 1H), 8.16 (d, J = 2.4 Hz, 1H), 7.67 (d, J = 8.8 Hz, 2H), 7.26 (d, J = 8.4 Hz, 2H), 7.14 (d, J = 8.4 Hz, 2H), 6.88 (d, J = 8.8 Hz, 2H), 6.43 (m, 1H), 6.26 (m, 1H), 5.77 (m, 1H), 4.79 ( s, 1H), 3.79 (s, 3H), 1.90 (m, 2H), 1.69 (m, 4H), 1.56 (m, 2H). 478 44 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N- (2,2-difluorocyclopropyl)-2-methoxybenzamide; ¹ H NMR (400 MHz, DMSO) δ 10.28 (s, 1H), 8.37 (s, 1H), 8.20 (d, J = 6.6 Hz, 1H), 7.69 (d, J = 8.5 Hz, 2H), 7.64 ( d, J = 7.8 Hz, 1H), 7.30 (d, J = 8.4 Hz, 2H), 6.96 (s, 1H), 6.90 (d, J = 8.0 Hz, 1H), 6.46 - 6.40 (m, 1H), 6.34 - 5.85 (m, 1H), 5.81-5.76 (m, 1H), 3.80 (s, 3H), 3.71 (s, 3H), 3.49 - 3.40 (m, 1H), 1.98 - 1.86 (m, 1H), 1.73 - 1.62 (m, 1H). 543 45 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N- (3-fluorocyclobutyl)-2-methoxybenzamide; ¹ H NMR (400 MHz, DMSO) δ 10.28 (s, 1H), 8.36 (d, J = 6.9 Hz, 1H), 8.21 (s, 1H), 7.69 (d, J = 8.5 Hz, 2H), 7.57 ( d, J = 7.8 Hz, 1H), 7.30 (d, J = 8.4 Hz, 2H), 6.95 - 6.86 (m, 2H), 6.43 (dd, J = 17.0, 10.1 Hz, 1H), 6.27 (d, J = 15.2 Hz, 1H), 5.78 (d, J = 12.0 Hz, 1H), 5.24 (d, J = 56.7 Hz, 1H), 4.50 (m, 1H), 3.80 (s, 3H), 3.71 (s, 3H ), 2.33 (m, 2H), 1.16 (m, 2H). 539 46 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2- Methoxy-N-(1-methylcyclopropyl)benzamide; ¹ H NMR (400 MHz, DMSO) δ 10.27 (s, 1H), 8.21 (d, J = 6.7 Hz, 2H), 7.69 (d, J = 8.4 Hz, 2H), 7.63 (d, J = 7.7 Hz, 1H), 7.29 (d, J = 8.5 Hz, 2H), 6.93 - 6.83 (m, 2H), 6.43 (dd, J = 17.0, 10.0 Hz, 1H), 6.26 (d, J = 17.2 Hz, 1H), 5.78 (d, J = 11.5 Hz, 1H), 3.80 (s, 3H), 3.70 (s, 3H), 1.35 (s, 3H), 0.70 (s, 2H), 0.58 (t, J = 5.6 Hz, 2H ). 521 47 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N- (Cyclopropylmethyl)-2-methoxybenzamide; ¹ H NMR (400 MHz, DMSO) δ 10.28 (s, 1H), 8.26 - 8.16 (m, 2H), 7.73 - 7.65 (m, 3H), 7.33 - 7.26 (m, 2H), 6.97 - 6.92 (m, 1H), 6.91 - 6.83 (m, 1H), 6.58 - 5.63 (m, 5H), 3.81 (s, 3H), 3.73 (s, 3H), 3.18 - 3.12 (m, 2H), 1.06 - 0.97 (m, 1H), 0.45 - 0.37 (m, 2H), 0.26 - 0.19 (m, 2H). 521 48 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; ¹ H NMR (400 MHz, DMSO) δ 10.41 (s, 1H), 8.20 (s, 1H), 8.05 (d, J = 4.2 Hz, 1H), 7.65- 7.52 (m, 2H), 7.34 (d, J = 8.2 Hz, 1H), 7.08 (d, J = 8.2 Hz, 1H), 6.85 (s, 2H), 6.09 (s, 2H), 5.80 - 5.67 (m, 1H), 5.49 - 5.44 (m, 1H) , 3.73 (s, 3H), 3.68 (s, 6H), 2.82 - 2.77 (m, 1H), 0.74-0.61 (m, 2H), 0.53 - 0.50 (m, 2H). 555 49 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; ¹ H NMR (400 MHz, DMSO) δ 8.67 (t, J = 6.4 Hz, 1H), 8.47 (d, J = 2.0 Hz, 1H), 8.25 (s, 1H), 7.85 (m, 1H), 7.70 ( d, J = 7.6 Hz, 1H), 7.63 (d, J = 8.0 Hz, 1H), 7.01 (s, 1H), 6.89 (m, 1H), 4.45 (s, 1H), 4.14 - 4.03 (m, 2H ), 3.85 (s, 3H), 3.76 (s, 3H). 505 50 4-(4-Amino-7-cyano-2-(6-ethynylpyridin-3-yl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl]-N -Cyclopropyl-2-methoxybenzamide; ¹ H NMR (400 MHz, DMSO) δ 8.46 (d, J = 1.6 Hz, 1H), 8.24 (s, 1H), 8.09 (d, J = 4.4 Hz, 1H), 7.86 (m, 1H), 7.61 ( m, 2H), 6.95 (s, 1H), 6.86 (m, 1H), 4.46 (s, 1H), 3.84 (s, 3H), 3.71 (s, 3H), 2.81 (m, 1H), 0.71 - 0.64 (m, 2H), 0.55 - 0.49 (m, 2H). 463 51 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N- (3,3-difluorocyclobutyl)-2-methoxybenzamide; ¹ H NMR (400 MHz, DMSO) δ 10.30 (s, 1H), 8.47 (s, 1H), 8.36 (s, 1H), 7.71 (d, J = 8.4 Hz, 2H), 7.63 (d, J = 7.6 Hz, 1H), 7.30 (d, J = 8.4 Hz, 2H), 6.96 (s, 1H), 6.88 (d, J = 8.0 Hz, 1H), 6.46-6.40 (m, 1H), 6.29-6.25 (m , 1H), 5.78-5.77 (m, 1H), 4.24 (s, 1H), 3.84 (s, 3H), 3.72 (s, 3H), 2.95 - 2.88 (m, 2H), 2.73-2.71 (m, 2H ). 557 52 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N- (2-fluoroethyl)-2-methoxybenzamide; ¹ H NMR (400 MHz, DMSO) δ 10.27 (s, 1H), 8.33 (t, J = 5.6 Hz, 1H), 8.22 (s, 1H), 7.75 - 7.64 (m, 3H), 7.30 (d, J = 8.4 Hz, 2H), 6.96 (s, 1H), 6.89 (d, J = 7.6 Hz, 1H), 6.46 - 6.39 (m, 1H), 6.33 - 5.84 (m, 3H), 5.79 - 5.76 (m, 1H), 4.57 (t, J = 5.2 Hz, 1H), 4.45 (t, J = 5.2 Hz, 1H), 3.81 (s, 3H), 3.74 (s, 3H), 3.62-3.58 (m, 1H), 3.56-3.52 (m, 1H). 513 53 N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H- Pyrro[3,2-c]pyridin-2-yl)phenyl)acrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.32 (s, 1H), 8.47 (d, J = 5.0 Hz, 1H), 8.35 (s, 1H), 7.74 (d, J = 8.5 Hz, 2H), 7.37 ( t, J = 8.3 Hz, 1H), 7.33 (d, J = 8.4 Hz, 2H), 7.26 (d, J = 11.1 Hz, 1H), 7.19 (d, J = 5.0 Hz, 1H), 7.12 (d, J = 8.3 Hz, 1H), 6.44 (dd, J = 16.9, 10.0 Hz, 1H), 6.28 (d, J = 15.4 Hz, 1H), 5.79 (d, J = 11.6 Hz, 1H), 3.84 (s, 3H), 2.41 (s, 3H). 520 54 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; ¹ H NMR (400 MHz, DMSO) δ 10.30 (s, 1H), 8.36 (s, 1H), 7.73 (d, J = 8.6 Hz, 2H), 7.69 - 7.63 (m, 1H), 7.32 (d, J = 8.6 Hz, 2H), 7.09 (d, J = 8.0 Hz, 1H), 6.99 (d, J = 1.8 Hz, 1H), 6.93 (d, J = 7.3 Hz, 1H), 6.83 (dd, J = 8.0 , 1.9 Hz, 1H), 6.64 (d, J = 8.2 Hz, 1H), 6.44 (dd, J = 17.0, 10.1 Hz, 1H), 6.27 (dd, J = 17.0, 1.9 Hz, 1H), 5.78 (dd , J = 10.1, 1.9 Hz, 1H), 3.87 (s, 3H), 3.56 (s, 3H), 2.28 (s, 3H) 531 55 4-(2-(1-(1-propenylpyridin-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; ¹ H NMR (400 MHz, DMSO) δ 8.68 (t, J = 6.4 Hz, 1H), 8.18 (s, 1H), 7.98 (s, 1H), 7.76 (d, J = 7.9 Hz, 1H), 7.43 ( s, 1H), 7.03 (s, 1H), 6.98 (d, J = 8.0 Hz, 1H), 6.84 (dd, J = 16.8, 10.5 Hz, 1H), 6.14 - 6.09 (m, 1H), 5.69 (dd , J = 10.4, 2.3 Hz, 1H), 4.47 (m, 2H), 4.11 (m, 3H), 3.87 (s, 3H), 3.80 (s, 3H), 3.23 (m, 1H), 2.82 (m, 1H), 2.03 (m, 2H), 1.76 (m, 2H). 607 56 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N- (2,2-difluoroethyl)-2-methoxybenzamide; ¹ H NMR (400 MHz, DMSO) δ 10.27 (s, 1H), 8.45 (t, J = 6.0 Hz, 1H), 8.21 (s, 1H), 7.71 (m, 3H), 7.29 (d, J = 8.4 Hz, 2H), 6.96 (s, 1H), 6.89 (d, J = 7.6 Hz, 1H), 6.43 (m, 1H), 6.32 - 5.94 (m, 4H), 5.77 (d, J = 10.0 Hz, 1H ), 3.81 (s, 3H), 3.74 (s, 3H), 3.68 (m, 2H). 531 57 4-(2-(1-Acrylylpyrrolidin-3-yl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) -2-Methoxy-N-(2,2,2-trifluoroethyl)benzamide; ¹ H NMR (400 MHz, MeOD) δ 8.07 - 7.95 (m, 2H), 7.22 - 7.10 (m, 2H), 6.58 - 6.18 (m, 1H), 6.17 - 6.08 (m, 1H), 5.74 - 5.45 ( m, 1H), 4.16 (m, 2H), 4.09 (s, 3H), 3.98 (m, 3H), 3.94 - 3.78 (m, 2H), 3.69 (m, 1H), 3.54 (m, 2H), 2.35 - 2.23 (m, 1H), 2.13 - 2.01 (m, 1H). 527 58 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N- ((1-fluorocyclopropyl)methyl)-2-methoxybenzamide; ¹ H NMR (400 MHz, DMSO) δ 10.28 (s, 1H), 8.40 (t, J = 5.9 Hz, 1H), 8.21 (s, 1H), 7.78 - 7.61 (m, 3H), 7.35 - 7.26 (m , 2H), 6.97 (d, J = 1.3 Hz, 1H), 6.89 (dd, J = 7.9, 1.4 Hz, 1H), 6.47 - 6.38 (m, 1H), 6.30 - 6.23 (m, 1H), 5.78 ( dd, J = 10.1, 2.0 Hz, 1H), 3.81 (s, 3H), 3.74 (s, 3H), 3.74 - 3.66 (m, 2H), 1.06 - 0.90 (m, 2H), 0.85 - 0.73 (m, 2H). 539 59 4-(2-(4-Acrylamide-3-fluorophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) -N-cyclopropyl-2-methoxybenzamide; ¹ H NMR (400 MHz, DMSO) δ 10.07 (s, 1H), 8.22 (s, 1H), 8.09 - 8.05 (m, 2H), 7.60 (d, J = 7.6 Hz, 1H), 7.35 - 7.32 (m , 1H), 7.17 - 7.15 (m, 1H), 6.96 (d, J = 1.2 Hz, 1H), 6.90 - 6.87 (m, 1H), 6.66 - 6.59 (m, 1H), 6.30 - 6.07 (m, 3H ), 5.80 - 5.77 (m, 1H), 3.82 (s, 3H), 3.72 (s, 3H), 2.83 - 2.78 (m, 1H), 0.68 - 0.66 (m, 2H), 0.53 - 0.51 (m, 2H ). 525 60 4-(2-(4-Acrylamide-3-fluorophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) -2-Methoxy-N-(2,2,2-trifluoroethyl)benzamide; ¹ H NMR (400 MHz, DMSO) δ 10.06 (s, 1H), 8.66 (t, J = 6.4 Hz, 1H), 8.23 (s, 1H), 8.08 (t, J = 8.2 Hz, 1H), 7.71 ( d, J = 8.0 Hz, 1H), 7.36 - 7.32 (m, 1H), 7.18 - 7.15 (m, 1H), 7.02 (d, J = 1.6 Hz, 1H), 6.93 - 6.90 (m, 1H), 6.66 - 6.59 (m, 1H), 6.44 - 5.86 (m, 3H), 5.81 - 5.78 (m, 1H), 4.11 - 4.07 (m, 2H), 3.83 (s, 3H), 3.77 (s, 3H). 567 61 4-(2-(1-propenyl-2,5-dihydro-1H-pyrrol-3-yl)-4-amino-7-cyano-1-methyl-1H-pyrrole [3,2- c]pyridin-3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; ¹ H NMR (400 MHz, MeOD) δ 8.11 (d, J = 1.3 Hz, 1H), 7.99 (dd, J = 7.9, 4.6 Hz, 1H), 7.19 (d, J = 1.4 Hz, 1H), 7.16 - 7.11 (m, 1H), 6.61 - 6.34 (m, 1H), 6.30 - 6.17 (m, 2H), 5.74 (m, 1H), 4.59 (dd, J = 5.8, 3.6 Hz, 1H), 4.41 (d, J = 2.1 Hz, 1H), 4.34 (s, 1H), 4.16 (m, 3H), 4.05 (d, J = 1.9 Hz, 3H), 3.97 (d, J = 2.9 Hz, 3H). 525 62 4-(4-amino-7-cyano-2-(4-(2-fluoroacrylamide)phenyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)-N- Cyclopropyl-2-methoxybenzamide; ¹ H NMR (400 MHz, DMSO) δ 12.48 (s, 1H), 10.36 (s, 1H), 8.18 - 8.11 (m, 2H), 7.70 - 7.64 (m, 3H), 7.38 - 7.33 (m, 2H) , 7.08 (d, J = 1.2 Hz, 1H), 6.96 (dd, J = 7.8, 1.4 Hz, 1H), 6.59 - 5.48 (m, 3H), 5.44 (dd, J = 15.6, 3.7 Hz, 1H), 3.77 (s, 3H), 2.88 - 2.80 (m, 1H), 0.73 - 0.67 (m, 2H), 0.58 - 0.54 (m, 2H). 511 63 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-(2-fluoroethyl)-1H-pyrrolo[3,2-c]pyridine-3- base)-N-cyclopropyl-2-methoxybenzamide; ¹ H NMR (400 MHz, DMSO) δ 10.28 (s, 1H), 8.22 (s, 1H), 8.05 (d, J = 4.4 Hz, 1H), 7.69 (d, J = 8.4 Hz, 2H), 7.56 ( d, J = 7.6 Hz, 1H), 7.33 (d, J = 8.4 Hz, 2H), 6.95 (d, J = 1.2 Hz, 1H), 6.88 (m, 1H), 6.43 (m, 1H), 6.27 ( m, 1H), 5.78 (m, 1H), 4.61 (m, 2H), 4.52 (s, 2H), 3.70 (s, 3H), 2.79 (m, 1H), 0.66 (m, 2H), 0.54 - 0.48 (m, 2H). 539 64 N-(4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) -2-methoxyphenyl)cyclopropanemethamide; ¹ H NMR (400 MHz, DMSO) δ 10.27 (s, 1H), 9.41 (s, 1H), 8.18 (s, 1H), 7.92 (d, J = 8.1 Hz, 1H), 7.68 (d, J = 8.6 Hz, 2H), 7.30 (d, J = 8.5 Hz, 2H), 6.86 (d, J = 1.6 Hz, 1H), 6.79 - 6.76 (m, 1H), 6.46 - 6.40 (m, 1H), 6.29 - 6.24 (m, 1H), 5.79 - 5.76 (m, 1H), 3.80 (s, 3H), 3.70 (s, 3H), 2.06 (d, J = 4.9 Hz, 1H), 0.76 - 0.74 (m, 4H). 507 65 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; ¹ H NMR (400 MHz, DMSO) δ 10.29 (s, 1H), 8.75 (s, 2H), 8.20 (s, 1H), 7.70 (d, J = 8.7 Hz, 2H), 7.33 - 7.30 (m, 4H ), 7.24 - 7.21 (m, 2H), 6.41 (d, J = 10.1 Hz, 1H), 6.27 (dd, J = 17.0, 2.0 Hz, 1H), 5.78 (dd, J = 10.1, 2.0 Hz, 1H) , 3.80 (s, 3H). 506 66 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-ethyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N- Cyclopropyl-2-methoxybenzamide; ¹ H NMR (400 MHz, DMSO) δ 10.29 (s, 1H), 8.23 (s, 1H), 8.05 (d, J = 4.3 Hz, 1H), 7.71 (d, J = 8.6 Hz, 2H), 7.56 ( d, J = 7.8 Hz, 1H), 7.35 (d, J = 8.5 Hz, 2H), 6.95 (d, J = 1.2 Hz, 1H), 6.89 -6.87 (m, 1H), 6.47 - 6.40 (m, 1H ), 6.30 - 6.25 (m, 1H), 5.80 - 5.77 (m, 1H), 4.24 - 4.19 (m, 2H), 3.69 (s, 3H), 2.82 - 2.77 (m, 1H), 1.23 (t, J = 7.0 Hz, 3H), 0.69 - 0.63 (m, 2H), 0.53 - 0.49 (m, 2H). 521 67 N-(4-(4-amino-7-cyano-3-(4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H- Pyrro[3,2-c]pyridin-2-yl)phenyl)acrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.29 (s, 1H), 8.55 (d, J = 1.3 Hz, 1H), 8.19 (s, 1H), 7.70 (d, J = 8.6 Hz, 2H), 7.31 ( d, J = 8.4 Hz, 4H), 7.22 - 7.17 (m, 2H), 6.48 - 6.39 (m, 1H), 6.27 (dd, J = 17.0, 2.0 Hz, 1H), 5.78 (dd, J = 10.1, 2.0 Hz, 1H), 3.80 (s, 3H), 2.40 (d, J = 2.5 Hz, 3H). 520 68 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; ¹ H NMR (400 MHz, DMSO) δ 10.30 (s, 1H), 8.37 (s, 1H), 7.70 (d, J = 8.6 Hz, 2H), 7.53 (d, J = 7.8 Hz, 1H), 7.29 ( t, J = 8.2 Hz, 2H), 6.92-6.87 (m, 2H), 6.46-6.39 (m, 1H), 6.28-6.24 (m, 1H), 5.78 (dd, J = 10.4, 2.0 Hz, 1H) , 4.73 (d, J = 7.2 Hz, 1H), 3.85 (s, 3H), 3.69 (s, 3H), 2.00 (s, 1H), 0.39 - 0.27 (m, 4H). 561 69 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N -(2,2,2-trifluoroethyl)benzamide; ¹ H NMR (400 MHz, DMSO) δ 12.48 (br s, 1H), 10.24 (s, 1H), 8.73 (t, J = 6.3 Hz, 1H), 8.14 (s, 1H), 7.79 (d, J = 7.8 Hz, 1H), 7.61 (d, J = 8.7 Hz, 2H), 7.33 (d, J = 8.7 Hz, 2H), 7.13 (d, J = 1.0 Hz, 1H), 7.00 (dd, J = 7.9, 1.2 Hz, 1H), 6.52 - 6.37 (m, 1H), 6.36 - 5.39 (m, 4H), 4.17 - 4.08 (m, 2H), 3.81 (s, 3H). 535 70 N-(4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) -2-methoxyphenyl)cyclobutamide; ¹ H NMR (400 MHz, DMSO) δ 10.26 (s, 1H), 8.86 (s, 1H), 8.18 (s, 1H), 7.99 (d, J = 8.0 Hz, 1H), 7.68 (d, J = 8.8 Hz, 2H), 7.29 (d, J = 8.8 Hz, 2H), 6.84 (d, J = 1.6 Hz, 1H), 6.79 (m, 1H), 6.43 (m, 1H), 6.26 (m, 1H), 5.77 (m, 1H), 3.80 (s, 3H), 3.67 (s, 3H), 3.45 - 3.36 (m, 1H), 2.24 - 2.14 (m, 2H), 2.07 (m, 2H), 1.95 - 1.76 ( m, 2H). 521 71 N-(4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) -2-methoxyphenyl)cyclopentamide; ¹ H NMR (400 MHz, DMSO) δ 10.26 (s, 1H), 8.98 (s, 1H), 8.18 (s, 1H), 7.97 (d, J = 8.0 Hz, 1H), 7.68 (d, J = 8.8 Hz, 2H), 7.29 (d, J = 8.4 Hz, 2H), 6.85 (d, J = 1.6 Hz, 1H), 6.80 - 6.76 (m, 1H), 6.43 (m, 1H), 6.26 (m, 1H ), 5.77 (m, 1H), 3.80 (s, 3H), 3.68 (s, 3H), 3.01 - 2.87 (m, 1H), 1.81 (m, 2H), 1.68 (m, 4H), 1.52 (s, 2H). 535 72 4-(4-Amino-7-cyano-2-(2-fluoro-4-(2-fluoroacrylamide)phenyl)-1H-pyrrolo[3,2-c]pyridin-3-yl )-N-cyclopropyl-2-methoxybenzamide; ¹ H NMR (400 MHz, DMSO) δ 12.64 (s, 1H), 10.55 (s, 1H), 8.17 (s, 1H), 8.10 (d, J = 4.3 Hz, 1H), 7.71 - 7.66 (m, 1H ), 7.63 - 7.60 (m, 1H), 7.52 - 7.48 (m, 1H), 7.33 - 7.28 (m, 1H), 6.99 - 6.96 (m, 1H), 6.90 - 6.87 (m, 1H), 6.57 - 5.53 (m, 3H), 5.48 (dd, J = 15.6, 3.7 Hz, 1H), 3.72 (s, 3H), 2.85 - 2.78 (m, 1H), 0.71 - 0.66 (m, 2H), 0.55 - 0.51 (m , 2H). 529 73 4-(2-(4-Acrylamide-2-methoxyphenyl)-4-amino-7-cyano-1H-pyrrolo[3,2-c]pyridin-3-yl)-N -(3,3-difluorocyclobutyl)-2-methoxybenzamide; ¹ H NMR (400 MHz, DMSO) δ 12.43 (s, 1H), 10.26 (s, 1H), 8.48 (d, J = 6.8 Hz, 1H), 8.16 (s, 1H), 7.63 (d, J = 7.8 Hz, 1H), 7.50 (s, 1H), 7.20 - 7.07 (m, 2H), 6.94 (s, 1H), 6.87 (d, J = 8.4 Hz, 1H), 6.46 - 6.39(m, 1H), 6.29 -6.25 (m, 1H), 5.80 - 5.77 (m, 1H), 4.31 - 4.17 (m, 1H), 3.73 (s, 3H), 3.58 (s, 3H), 3.00 - 2.85 (m, 2H), 2.82 - 2.64 (m, 2H). 573 74 N-(4-(4-amino-7-cyano-3-(3-methoxy-4-propylamidophenyl)-1-methyl-1H-pyrrolo[3,2-c] Pyridin-2-yl)phenyl)acrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.29 (s, 1H), 9.06 (s, 1H), 8.38 (s, 1H), 8.03 (d, J = 8.1 Hz, 1H), 7.70 (d, J = 8.6 Hz, 2H), 7.29 (d, J = 8.6 Hz, 2H), 6.85 (d, J = 1.8 Hz, 1H), 6.79 (dd, J = 8.2, 1.8 Hz, 1H), 6.43 (dd, J = 17.0 , 10.1 Hz, 1H), 6.27 (dd, J = 17.0, 2.0 Hz, 1H), 5.78 (dd, J = 10.1, 2.0 Hz, 1H), 3.86 (s, 3H), 3.68 (s, 3H), 2.39 (q, J = 7.5 Hz, 2H), 1.05 (t, J = 7.5 Hz, 3H). 495 75 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-(2-fluoroethyl)-1H-pyrrolo[3,2-c]pyridine-3- base)-N-(3,3-difluorocyclobutyl)-2-methoxybenzamide; ¹ H NMR (400 MHz, DMSO) δ 10.28 (s, 1H), 8.48 (d, J = 6.8 Hz, 1H), 8.23 (s, 1H), 7.69 (d, J = 8.4 Hz, 2H), 7.58 ( d, J = 8.0 Hz, 1H), 7.33 (d, J = 8.4 Hz, 2H), 6.98 (s, 1H), 6.89 (d, J = 8.0 Hz, 1H), 6.43 (m, 1H), 6.27 ( m, 2H), 5.78 (dd, J = 10.0, 1.9 Hz, 1H), 4.66 - 4.58 (m, 2H), 4.53 (s, 2H), 4.22 (m, 1H), 3.72 (s, 4H), 2.94 - 2.86 (m, 2H), 2.74 - 2.66 (m, 3H). 589 76 4-(2-(4-Acrylamide-2-fluorophenyl)-4-amino-7-cyano-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-(3 ,3-difluorocyclobutyl)-2-methoxybenzamide; ¹ H NMR (400 MHz, MeOD) δ 8.09 (s, 1H), 7.82 (d, J = 8.3 Hz, 1H), 7.70 (dd, J = 12.4, 1.9 Hz, 1H), 7.29 - 7.18 (m, 2H ), 7.09 - 6.99 (m, 2H), 6.40 (dd, J = 7.4, 3.5 Hz, 2H), 5.80 (dd, J = 7.7, 4.1 Hz, 1H), 4.36 - 4.28 (m, 1H), 3.82 ( s, 3H), 3.02 - 2.94 (m, 2H), 2.72 - 2.62 (m, 2H). 561 77 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-isopropyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N -(3,3-difluorocyclobutyl)-2-methoxybenzamide; ¹ H NMR (400 MHz, DMSO) δ 10.28 (s, 1H), 8.46 (d, J = 6.4 Hz, 1H), 8.22 (s, 1H), 7.68 (d, J = 8.8 Hz, 2H), 7.56 ( d, J = 7.6 Hz, 1H), 7.35 (s, 2H), 6.95 (s, 1H), 6.89 (d, J = 8.0 Hz, 1H), 6.42 (dd, J = 16.8, 10.0 Hz, 1H), 6.26 (dd, J = 16.8, 2.0 Hz, 1H), 5.78 (dd, J = 10.0, 2.0 Hz, 1H), 4.72-5.12 (m,1H), 4.27 - 4.15 (m, 1H), 3.70 (s, 3H), 2.98 - 2.82 (m, 2H), 2.78 - 2.65 (m, 2H), 1.47 (s, 6H). 585 78 N-(4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) -2-methoxyphenyl)-N-methylcyclopropanemethamide; ¹ H NMR (400 MHz, DMSO) δ 10.27 (s, 1H), 8.20 (s, 1H), 7.65 (s, 2H), 7.27 (s, 3H), 6.90 (d, J = 38.7 Hz, 2H), 6.41 (d, J = 10.1 Hz, 1H), 6.26 (d, J = 16.9 Hz, 3H), 5.78 (d, J = 9.7 Hz, 1H), 3.83 (s, 3H), 3.65 (s, 3H), 3.04 (s, 3H), 1.16 (m, 1H), 0.69 (s, 2H), 0.53 (s, 2H). 521 79 N-(4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) Phenyl)cyclopropanemethamide; ¹ H NMR (400 MHz, MeOD) δ 8.27 (s, 1H), 7.70 (d, J = 8.8 Hz, 2H), 7.57 (d, J = 8.4 Hz, 2H), 7.26 (dd, J = 16.0, 8.4 Hz, 4H), 6.49 - 6.31 (m, 2H), 5.79 (dd, J = 9.2, 2.8 Hz, 1H), 4.02 (s, 3H), 1.80 - 1.69 (m, 1H), 0.97 - 0.90 (m, 2H), 0.90 - 0.82 (m, 2H). 477 80 N-(4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) -2-methoxyphenyl)-3,3-difluorocyclobutane-1-methamide; ¹ H NMR (400 MHz, DMSO) δ 10.30 (s, 1H), 9.39 (s, 1H), 8.40 (s, 1H), 8.04 (d, J = 8.4 Hz, 1H), 7.70 (d, J = 8.4 Hz, 2H), 7.29 (d, J = 8.4 Hz, 2H), 6.87 (d, J = 1.6 Hz, 1H), 6.80 (dd, J = 8.4, 1.6 Hz, 1H), 6.43 (dd, J = 16.0 , 10. Hz, 1H), 6.27 (dd, J = 16.0, 2.0 Hz, 1H), 5.78 (dd, J = 10., 2.0 Hz, 1H), 3.86 (s, 4H), 3.69 (s, 3H) , 3.37 - 3.30 (m, 1H), 2.80 - 2.70 (m, 4H). 557 81 N-(4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) -2-methoxyphenyl)-1-methylcyclopropane-1-methamide; ¹ H NMR (400 MHz, DMSO) δ 10.26 (s, 1H), 8.42 (s, 1H), 8.19 (s, 1H), 7.87 (d, J = 8.1 Hz, 1H), 7.68 (d, J = 8.6 Hz, 2H), 7.30 (d, J = 8.6 Hz, 2H), 6.89 (d, J = 1.7 Hz, 1H), 6.80 (dd, J = 8.1, 1.7 Hz, 1H), 6.43 (dd, J = 16.9 , 10.1 Hz, 1H), 6.26 (dd, J = 17.0, 2.0 Hz, 1H), 5.77 (dd, J = 10.1, 2.0 Hz, 1H), 3.81 (s, 3H), 3.71 (s, 3H), 1.39 (s, 3H), 1.06 (q, J = 3.5 Hz, 2H), 0.65 (q, J = 3.7 Hz, 2H). 521 82 N-(4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) -2-methoxyphenyl)-1-fluorocyclopropane-1-methamide; ¹ H NMR (400 MHz, DMSO) δ 10.27 (s, 1H), 9.06 (d, J = 3.6 Hz, 1H), 8.19 (s, 1H), 7.86 (d, J = 8.0 Hz, 1H), 7.69 ( d, J = 8.8 Hz, 2H), 7.31 (d, J = 8.4 Hz, 2H), 6.95 (d, J = 1.6 Hz, 1H), 6.84 (m, 1H), 6.43 (m, 1H), 6.26 ( m, 1H), 5.77 (m, 1H), 3.80 (s, 3H), 3.73 (s, 3H), 1.43 (m, 2H), 1.30 (m, 2H). 525 83 N-(4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) -2-methoxyphenyl)-1-(trifluoromethyl)cyclopropane-1-methamide; ¹ H NMR (400 MHz, DMSO) δ 10.27 (s, 1H), 8.76 (s, 1H), 8.19 (s, 1H), 7.72 (d, J = 8.0 Hz, 1H), 7.68 (d, J = 8.4 Hz, 2H), 7.30 (d, J = 8.4 Hz, 2H), 6.93 (d, J = 1.6 Hz, 1H), 6.82 (dd, J = 8.0, 1.6 Hz, 1H), 6.43 (dd, J = 17.2 , 10.1 Hz, 1H), 6.26 (dd, J = 17.2, 2.0 Hz, 1H), 5.77 (dd, J = 10.0, 2.0 Hz, 1H), 3.80 (s, 3H), 3.70 (s, 3H), 1.45 (7.6, 5.2 Hz, 2H), 1.34 (dd, J = 7.6, 5.2 Hz, 2H). 576 84 N-(4-(4-amino-7-cyano-3-(4-cyclobutoxy-3-methoxyphenyl)-1-methyl-1H-pyrrolo[3,2-c] Pyridin-2-yl)phenyl)acrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.26 (s, 1H), 8.17 (s, 1H), 7.68 (d, J = 8.6 Hz, 2H), 7.29 (d, J = 8.6 Hz, 2H), 6.79 - 6.70 (m, 3H), 6.43 (dd, J = 17.0, 10.1 Hz, 1H), 6.27 (dd, J = 17.0, 1.9 Hz, 1H), 5.78 (dd, J = 10.1, 2.0 Hz, 1H), 4.61 (p, J = 7.1 Hz, 1H), 3.79 (s, 3H), 3.61 (s, 3H), 2.42 -2.36 (m, 2H), 2.09 - 1.99 (m, 2H), 1.82 - 1.53 (m, 2H ). 494 85 N-(4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) -2-methoxyphenyl)-2,2-difluorocyclopropane-1-methamide; ¹ H NMR (400 MHz, DMSO) δ 10.26 (s, 1H), 9.73 (s, 1H), 8.18 (d, J = 1.9 Hz, 1H), 7.94 (d, J = 8.2 Hz, 1H), 7.68 ( d, J = 8.5 Hz, 2H), 7.30 (d, J = 8.5 Hz, 2H), 6.88 (s, 1H), 6.80 (d, J = 8.2 Hz, 1H), 6.43 (dd, J = 16.9, 10.1 Hz, 1H), 6.26 (dd, J = 17.0, 1.8 Hz, 1H), 5.77 (dd, J = 10.1, 1.9 Hz, 1H), 3.80 (s, 3H), 3.71 (s, 3H), 3.18 - 3.09 (m, 1H), 2.00 - 1.88 (m, 2H). 543 86 N-(4-(4-amino-7-cyano-3-(4-(3-cyclopropylureido)-3-methoxyphenyl)-1-methyl-1H-pyrrolo[3 ,2-c]pyridin-2-yl)phenyl)acrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.26 (s, 1H), 8.17 (s, 1H), 8.07 (d, J = 8.2 Hz, 1H), 7.82 (s, 1H), 7.68 (d, J = 8.6 Hz, 2H), 7.29 (d, J = 8.6 Hz, 2H), 7.05 (d, J = 2.8 Hz, 1H), 6.79 (s, 1H), 6.77 - 6.71 (m, 1H), 6.48 - 6.38 (m , 1H), 6.30 - 6.22 (m, 1H), 5.81 - 5.73 (m, 1H), 3.80 (s, 3H), 3.68 (s, 3H), 2.55 - 2.52 (m, 1H), 0.65 - 0.60 (m , 2H), 0.39 - 0.34 (m, 2H). 522 87 N-(4-(4-amino-7-cyano-3-(4-(cyclobutylamino)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2- Base)phenyl)acrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.25 (s, 1H), 8.13 (d, J = 2.6 Hz, 1H), 7.67 (d, J = 8.5 Hz, 2H), 7.27 (d, J = 8.5 Hz, 2H), 6.94 (d, J = 8.4 Hz, 2H), 6.52 - 6.38 (m, 3H), 6.27 (d, J = 16.9 Hz, 1H), 6.05 (d, J = 6.5 Hz, 1H), 5.77 ( d, J = 9.9 Hz, 1H), 3.84 - 3.72 (m, 4H), 2.36 - 2.24 (m, 2H), 1.83 - 1.66 (m, 4H). 463 88 N-(4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) -2-methoxyphenyl)azetidine-1-methamide; ¹ H NMR (400 MHz, DMSO) δ 10.26 (s, 1H), 8.18 (s, 1H), 7.80 (d, J = 8.1 Hz, 1H), 7.67 (d, J = 8.6 Hz, 2H), 7.29 ( d, J = 8.6 Hz, 2H), 7.18 (s, 1H), 6.82 (d, J = 1.7 Hz, 1H), 6.79 - 6.76 (m, 1H), 6.46 - 6.39 (m, 1H), 6.29 - 6.24 (m, 1H), 5.79 - 5.76 (m, 1H), 3.94 (t, J = 7.6 Hz, 4H), 3.80 (s, 3H), 3.67 (s, 3H), 2.20 - 2.13 (m, 2H). 522 89 4-(2-(4-Acrylamide-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; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.76 (s, 1H), 8.60 (t, J = 6.4 Hz, 1H), 8.22 (s, 1H), 8.14 (d, J = 8.3 Hz, 1H) , 7.72 (d, J = 7.8 Hz, 1H), 7.33 (dd, J = 8.3, 2.1 Hz, 1H), 7.09 (d, J = 2.1 Hz, 1H), 6.96 - 6.87 (m, 2H), 6.32 ( dd, J = 17.1, 10.1 Hz, 1H), 6.20 (dd, J = 17.0, 1.7 Hz, 1H), 5.80 (dd, J = 10.1, 1.7 Hz, 1H), 4.20 - 4.01 (m, 2H), 3.84 (s, 2H), 3.72 (s, 3H), 3.42 (s, 2H), 2.07 (s, 5H). 606 90 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; ¹ H NMR (400 MHz, DMSO) δ 10.42 (s, 1H), 8.46 (d, J = 5.0 Hz, 1H), 8.19 (d, J = 5.5 Hz, 2H), 7.78 (d, J = 8.6 Hz, 2H), 7.35 - 7.30 (m, 4H), 7.20 - 7.14 (m, 3H), 5.99 (s, 1H), 5.79 - 5.66 (m, 1H), 5.48 - 5.43 (m, 1H), 3.81 (s, 3H), 2.40 (s, 3H). 520 91 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; ¹ H NMR (400 MHz, DMSO) δ 12.99 - 12.51 (m, 1H), 10.36 (s, 1H), 8.73 (t, J = 6.4 Hz, 1H), 8.14 (s, 1H), 7.80 (d, J = 7.9 Hz, 1H), 7.67 (d, J = 8.8 Hz, 2H), 7.35 (d, J = 8.7 Hz, 2H), 7.14 (d, J = 1.1 Hz, 1H), 6.99 (dd, J = 7.9 , 1.3 Hz, 1H), 6.20 (br s, 2H), 5.71 (dd, J = 47.7, 3.7 Hz, 1H), 5.44 (dd, J = 15.6, 3.7 Hz, 1H), 4.18 - 4.08 (m, 2H ), 3.82 (s, 3H). 553 92 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; ¹ H NMR (400 MHz, DMSO) δ 12.50 (s, 1H), 10.36 (s, 1H), 8.77 (s, 1H), 8.15 (s, 1H), 7.66 (d, J = 5.2 Hz, 3H), 7.35 (d, J = 8.1 Hz, 2H), 7.10 (s, 1H), 6.97 (d, J = 7.6 Hz, 1H), 5.71 (d, J = 45.6 Hz, 1H), 5.44 (d, J = 14.9 Hz, 1H), 3.79 (s, 3H), 1.32 (m, 2H), 1.18 (m, 2H). 579 93 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-(2-methoxyethyl)-1H-pyrrolo[3,2-c]pyridine- 3-yl)-N-(3,3-difluorocyclobutyl)-2-methoxybenzamide; ¹ H NMR (400 MHz, DMSO) δ 10.28 (s, 1H), 8.47 (d, J = 6.8 Hz, 1H), 8.21 (s, 1H), 7.69 (d, J = 8.5 Hz, 2H), 7.58 ( d, J = 7.8 Hz, 1H), 7.34 (d, J = 8.5 Hz, 2H), 6.94 (s, 1H), 6.89 (d, J = 7.8 Hz, 1H), 6.43 (dd, J = 17.0, 10.1 Hz, 1H), 6.27 (dd, J = 17.0, 1.9 Hz, 1H), 5.78 (dd, J = 10.1, 1.9 Hz, 1H), 4.40 (t, J = 5.6 Hz, 2H), 3.71 (s, 3H ), 3.51 (t, J = 5.8 Hz, 2H), 3.07 (s, 3H), 2.95 - 2.86 (m, 2H), 2.77 - 2.64 (m, 2H). 601 94 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-(2-fluoroethyl)-1H-pyrrolo[3,2-c]pyridine-3- base)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; ¹ H NMR (400 MHz, DMSO) δ 10.28 (s, 1H), 8.64 (t, J = 6.4 Hz, 1H), 8.23 (s, 1H), 7.68 (m, 3H), 7.33 (d, J = 8.8 Hz, 2H), 7.01 (d, J = 1.2 Hz, 1H), 6.90 (m, 1H), 6.43 (m, 1H), 6.27 (m, 1H), 5.78 (m, 1H), 4.60 (m, 4H ), 4.12 - 4.03 (m, 2H), 3.74 (s, 3H). 581 95 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2- Methoxy-N-(1-(trifluoromethyl)cyclopropyl)benzamide; ¹ H NMR (400 MHz, DMSO) δ 10.28 (s, 1H), 8.68 (s, 1H), 8.21 (s, 1H), 7.69 (d, J = 8.4 Hz, 2H), 7.56 (d, J = 8 Hz, 1H), 7.30 (d, J = 8.4 Hz, 2H), 6.95 (s, 1H), 6.87 (d, J = 7.6 Hz, 1H), 6.43 (m, 1H), 6.27 (m, 1H), 5.78 (m, 1H), 3.80 (s, 3H), 3.71 (s, 3H), 1.24 (m, 2H), 1.13 (m, 2H). 575 96 N-(4-(4-amino-7-cyano-1-methyl-3-(4-(pyrrolidin-1-yl)phenyl)-1H-pyrrolo[3,2-c]pyridine- 2-yl)phenyl]acrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.27 (s, 1H), 8.31 (s, 1H), 7.68 (d, J = 8.4 Hz, 2H), 7.27 (d, J = 8.4 Hz, 2H), 7.04 ( d, J = 8.4 Hz, 2H), 6.52 (d, J = 8.4 Hz, 2H), 6.43 (dd, J = 17.2, 10.0 Hz, 1H), 6.26 (dd, J = 17.2, 2.0 Hz, 1H), 5.78 (dd, J = 10.0, 2.0 Hz, 1H), 3.84 (s, 3H), 3.22 (t, J = 6.4 Hz, 4H), 1.94 (t, J = 6.4 Hz, 4H). 463 97 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; ¹ H NMR (400 MHz, DMSO) δ 10.27 (s, 1H), 8.15 (s, 1H), 7.68 (d, J = 8.0 Hz, 2H), 7.30 (d, J = 8.4 Hz, 2H), 6.70 ( d, J = 8.8 Hz, 2H), 6.61 (d, J = 8.4 Hz, 1H), 6.43 (m, 1H), 6.26 (d, J = 16.4 Hz, 1H), 5.77 (d, J = 10.0 Hz, 1H), 3.79 (s, 3H), 3.59 (s, 3H), 3.25 (s, 4H), 1.82 (s, 4H). 493 98 N-(4-(4-amino-7-cyano-3-(4-(cyclobutylamino)-3-methoxyphenyl)-1-methyl-1H-pyrrolo[3,2- c]pyridin-2-yl)phenyl)acrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.26 (s, 1H), 8.14 (s, 1H), 7.67 (d, J = 8.6 Hz, 2H), 7.29 (d, J = 8.6 Hz, 2H), 6.65 ( d, J = 7.6 Hz, 2H), 6.48 - 6.39 (m, 2H), 6.26 (dd, J = 17.0, 1.9 Hz, 1H), 5.77 (dd, J = 10.1, 1.9 Hz, 1H), 5.02 (d , J = 6.9 Hz, 1H), 3.88 - 3.78 (m, 1H), 3.78 (s, 3H), 3.63 (s, 3H), 1.95 - 1.82 (m, 2H), 1.68 (dt, J = 17.9, 7.4 Hz, 2H), 1.26 - 1.06 (m, 2H). 493 99 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-(2-methoxyethyl)-1H-pyrrolo[3,2-c]pyridine- 3-yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; ¹ H NMR (400 MHz, DMSO) δ 10.27 (s, 1H), 8.63 (t, J = 6.4 Hz, 1H), 8.22 (s, 1H), 7.71 - 7.65 (m, 3H), 7.33 (d, J = 8.6 Hz, 2H), 6.98 (d, J = 1.2 Hz, 1H), 6.90 (dd, J = 7.9, 1.4 Hz, 1H), 6.43 (dd, J = 17.0, 10.1 Hz, 1H), 6.27 (dd , J = 17.0, 2.0 Hz, 1H), 5.78 (dd, J = 10.1, 2.0 Hz, 1H), 4.41 (t, J = 5.7 Hz, 2H), 4.12 - 4.03 (m, 2H), 3.73 (s, 3H), 3.51 (t, J = 5.7 Hz, 2H), 3.08 (s, 3H). 593 100 4-(4-amino-7-cyano-2-(4-(2-fluoroacrylamide)phenyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)-N- (3,3-difluorocyclobutyl)-2-methoxybenzamide; ¹ H NMR (400 MHz, DMSO) δ 12.75 (br s, 1H), 12.54 (s, 1H), 10.36 (s, 1H), 8.57 (d, J = 6.7 Hz, 1H), 8.16 (s, 1H) , 8.13 (s, 1H), 7.83 - 7.56 (m, 3H), 7.35 (d, J = 8.5 Hz, 2H), 7.10 (s, 1H), 6.98 (d, J = 7.8 Hz, 1H), 5.71 ( dd, J = 47.6, 3.5 Hz, 1H), 5.44 (dd, J = 15.6, 3.5 Hz, 1H), 4.38 - 4.17 (m, 1H), 3.79 (s, 3H), 3.04 - 2.87 (m, 2H) , 2.83 - 2.66 (m, 2H). 561 101 4-(4-amino-7-cyano-2-(4-(2-fluoroacrylamide)phenyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)-N- (2,2-difluorocyclopropyl)-2-methoxybenzamide; ¹ H NMR (400 MHz, DMSO) δ 12.50 (s, 1H), 10.35 (s, 1H), 8.46 (s, 1H), 8.14 (s, 1H), 7.73 (d, J = 7.8 Hz, 1H), 7.66 (d, J = 8.6 Hz, 2H), 7.35 (d, J = 8.7 Hz, 2H), 7.11 (s, 1H), 6.99 (d, J = 8.0 Hz, 1H), 5.77 (d, J = 3.6 Hz, 0.5H), 5.65 (d, J = 3.5 Hz, 0.5H), 5.44 (dd, J = 15.6, 3.6 Hz, 1H), 3.79 (s, 3H), 3.47 (m, 1H), 1.95 (m , 1H), 1.71 (m, 1H). 547 102 4-(4-amino-7-cyano-2-(4-(2-fluoroacrylamide)phenyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)-2- Methoxy-N-(1-methylcyclopropyl)benzamide; ¹ H NMR (400 MHz, DMSO) δ 12.48 (s, 1H), 10.35 (s, 1H), 8.31 (s, 1H), 8.16 - 8.13 (m, 1H), 7.73 (d, J = 7.8 Hz, 1H ), 7.66 (d, J = 8.7 Hz, 2H), 7.34 (d, J = 8.7 Hz, 2H), 7.07 (s, 1H), 6.95 (d, J = 7.8 Hz, 1H), 5.77 (d, J = 3.7 Hz, 0.5H), 5.65 (d, J = 3.7 Hz, 0.5H), 5.44 (dd, J = 15.6, 3.7 Hz, 1H), 3.78 (s, 3H), 1.39 (s, 3H), 0.74 (m, 2H), 0.61 (m, 2H). 525 103 N-(4-(4-amino-7-cyano-1-methyl-3-(1-methyl-1H-indol-5-yl)-1H-pyrrolo[3,2-c]pyridine -2-yl)phenyl)acrylamide; ¹ H NMR (400 MHz, MeOD) δ 8.07 (s, 1H), 7.59 (d, J = 8.6 Hz, 2H), 7.47 (s, 1H), 7.37 (d, J = 8.4 Hz, 1H), 7.27 ( d, J = 8.6 Hz, 2H), 7.19 (d, J = 3.2 Hz, 1H), 7.10 - 7.02 (m, 1H), 6.42 - 6.32 (m, 3H), 5.75 (dd, J = 9.3, 2.5 Hz , 1H), 3.94 (s, 3H), 3.80 (s, 3H). 447 104 N-(4-(4-amino-3-(benzo[b]thiophen-2-yl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridine-2- Base)phenyl)acrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.28 (s, 1H), 8.23 (s, 1H), 7.87 (dd, J = 18.8, 7.8 Hz, 2H), 7.69 (d, J = 8.5 Hz, 2H), 7.43 - 7.32 (m, 5H), 6.45 - 6.38 (m, 1H), 6.25 (d, J = 16.8 Hz, 1H), 5.77 (d, J = 10.0 Hz, 1H), 3.82 (s, 3H). 450 105 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-isopropyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2 -Methoxy-N-(2,2,2-trifluoroethyl)benzamide; ¹ H NMR (400 MHz, DMSO) δ 10.29 (s, 1H), 8.62 (t, J = 6.4 Hz, 1H), 8.30 (s, 1H), 7.72 - 7.63 (m, 3H), 7.35 (s, 2H ), 6.99 (s, 1H), 6.91 (d, J = 9.2 Hz, 1H), 6.43 (m, 1H), 6.27 (m, 1H), 5.82 - 5.74 (m, 1H), 4.08 (d, J = 7.4 Hz, 2H), 3.73 (s, 3H), 3.60 (s, 1H), 1.47 (s, 6H). 577 106 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-c ]pyridin-3-yl)-2-methoxy-N-(2,2-difluoroethyl)benzamide; ¹ H NMR (400 MHz, DMSO) δ 10.30 (s, 1H), 8.65 (s, 1H), 8.32 (s, 1H), 7.69 (m, 3H), 7.31 (d, J = 8.3 Hz, 2H), 6.98 (d, J = 63.0 Hz, 2H), 6.43 (m,1H), 6.30 - 6.24 (m, 1H), 5.78 (d, J = 12.0 Hz, 1H), 5.13 (s, 2H), 4.10 - 4.02 (m, 2H), 3.76 (s, 3H). 617 107 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; ¹ H NMR (400 MHz, DMSO) δ 10.30 (s, 1H), 8.44 (s, 1H), 8.36 (s, 1H), 7.71 (d, J = 8.6 Hz, 2H), 7.64 (d, J = 7.8 Hz, 1H), 7.29 (d, J = 8.5 Hz, 2H), 6.94 (s, 1H), 6.87 (d, J = 7.8 Hz, 1H), 6.41 (d, J = 10.1 Hz, 1H), 6.29 ( d, J = 1.8 Hz, 1H), 5.78 (m, 1H), 3.84 (s, 3H), 3.71 (s, 3H), 2.44 (s, 1H), 2.05 (s, 6H). 533 108 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; ¹ H NMR (400 MHz, DMSO) δ 10.29 (s, 1H), 8.31 (s, 1H), 8.06 (d, J = 4.4 Hz, 1H), 7.70 (d, J = 8.5 Hz, 2H), 7.56 ( d, J = 7.8 Hz, 1H), 7.31 (d, J = 8.2 Hz, 2H), 7.00 (s, 1H), 6.86 (s, 1H), 6.40 (d, J = 10.1 Hz, 1H), 6.29 ( d, J = 1.9 Hz, 1H), 5.80 (m, 1H), 5.13 (s, 2H), 3.72 (s, 3H), 2.79 (m,1H), 0.69 - 0.64 (m, 2H), 0.53 - 0.48 (m, 2H). 575 109 N-(4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) -2-Fluorophenyl)cyclopropanecarboxamide; ¹ H NMR (400 MHz, DMSO) δ 10.30 (s, 1H), 10.02 (s, 1H), 8.34 (s, 1H), 7.97 (t, J = 8.4 Hz, 1H), 7.71 (d, J = 8.4 Hz, 2H), 7.27 (d, J = 8.4 Hz, 2H), 7.10 (dd, J = 11.6, 1.7 Hz, 1H), 7.00 (d, J = 10.0 Hz, 1H), 6.43 (dd, J = 16.8 , 10.0 Hz, 1H), 6.27 (dd, J = 17.2, 2.0 Hz, 1H), 5.78 (dd, J = 10.0, 2.0 Hz, 1H), 3.83 (s, 3H), 2.05 - 1.99 (m, 1H) , 0.79 (d, J = 6.4 Hz, 4H). 495 110 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-cyclopropyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2 -Methoxy-N-(2,2,2-trifluoroethyl)benzamide; ¹ H NMR (400 MHz, DMSO) δ 10.27 (s, 1H), 8.66 (t, J = 6.4 Hz, 1H), 8.40 (s, 1H), 7.74 (dd, J = 8.4, 3.6 Hz, 1H), 7.67 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 8.4 Hz, 2H), 7.04 (s, 1H), 6.89 - 6.82 (m, 1H), 6.48 - 6.37 (m, 1H), 6.26 (dd, J = 17.2, 2.0 Hz, 1H), 5.78 (dd, J = 10.0, 1.6 Hz, 1H), 4.09 (dd, J = 16.0, 9.2 Hz, 2H), 3.87 (m, 1H), 3.77 ( s, 3H), 0.96 (d, J = 6.4 Hz, 2H), 0.69 (s, 2H). 575 111 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2- (Methylthio)-N-(2,2,2-trifluoroethyl)benzamide; ¹ H NMR (400 MHz, DMSO) δ 10.30 (s, 1H), 9.02 (t, J = 16.0 Hz, 1H), 8.22 (s, 1H), 7.70 (d, J = 12.0 Hz, 2H), 7.43 ( d, J = 8.0 Hz, 1H), 7.30 (d, J = 8.0 Hz, 2H), 7.12 (s, 1H), 7.10 - 7.06 (m, 1H), 6.43 (m, 1H), 6.27 (m, 1H ), 5.78 (m, 1H), 4.05 - 3.97 (m, 2H), 3.80 (s, 3H), 2.18 (s, 3H). 565 112 N-(4-(4-amino-7-cyano-3-(3-methoxy-4-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl) (yl)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.28 (s, 1H), 8.56 (t, J = 6.4 Hz, 1H), 8.19 (s, 1H), 7.68 (d, J = 8.4 Hz, 2H), 7.31 ( d, J = 8.8 Hz, 2H), 7.14 (d, J = 7.6 Hz, 1H), 6.89 - 6.73 (m, 2H), 6.43 (m, 1H), 6.27 (m, 1H), 5.77 (m, 1H ), 3.90 (m, 2H), 3.79 (s, 3H), 3.61 (s, 3H), 3.46 (s, 2H). 563 113 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-cyclopropyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N -Cyclopropyl-2-methoxybenzamide; ¹ H NMR (400 MHz, DMSO) δ 10.25 (s, 1H), 8.29 (s, 1H), 8.08 (d, J = 4.4 Hz, 1H), 7.65 (d, J = 8.4 Hz, 2H), 7.61 ( d, J = 7.6 Hz, 1H), 7.33 (d, J = 8.4 Hz, 2H), 6.96 (s, 1H), 6.84 (d, J = 7.6 Hz, 1H), 6.43 (dd, J = 16.8, 10.0 Hz, 1H), 6.26 (d, J = 16.8 Hz, 1H), 5.78 (d, J = 10.0 Hz, 1H), 3.87 (m, 1H), 3.71 (s, 3H), 2.81 (d, J = 4.4 Hz, 1H), 0.94 (d, J = 6.4 Hz, 2H), 0.68 (d, J = 5.2 Hz, 4H), 0.53 (s, 2H). 533 114 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; ¹ H NMR (400 MHz, DMSO) δ 10.30 (s, 1H), 8.21 (s, 1H), 7.78 - 7.67 (m, 3H), 7.31 - 7.20 (m, 4H), 7.08 (dd, J = 8.2, 1.6 Hz, 1H), 7.00 (d, J = 7.2 Hz, 1H), 6.86 (d, J = 8.2 Hz, 1H), 6.44 (dd, J = 17.0, 10.1 Hz, 1H), 6.27 (dd, J = 17.0, 2.0 Hz, 1H), 5.78 (dd, J = 10.0, 2.0 Hz, 1H), 3.82 (s, 3H), 2.28 (s, 3H). 519 115 N-(4-(4-amino-7-cyano-3-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)-3-fluorophenyl)-1-methyl Base-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.31 (s, 1H), 8.89 (d, J = 5.2 Hz, 1H), 8.21 (s, 1H), 7.73 (d, J = 8.4 Hz, 2H), 7.59 ( d, J = 5.2 Hz, 1H), 7.44 (t, J = 8.4 Hz, 1H), 7.32 (d, J = 8.4 Hz, 2H), 7.27 (s, 1H), 7.15 (d, J = 8.8 Hz, 1H), 6.93 (t, J = 54.2 Hz, 1H), 6.44 (dd, J = 17.2, 10.2 Hz, 1H), 6.28 (d, J = 17.2 Hz, 1H), 5.78 (d, J = 10.2 Hz, 1H). 556 116 N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl Base-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl]acrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.31 (s, 1H), 8.56 (d, J = 1.2 Hz, 1H), 8.21 (s, 1H), 7.73 (d, J = 8.8 Hz, 2H), 7.37 ( t, J = 8.4 Hz, 1H), 7.32 (d, J = 8.8 Hz, 2H), 7.25 (dd, J = 11.2, 1.9 Hz, 1H), 7.12 (dd, J = 8.4, 1.2 Hz, 1H), 6.44 (dd, J = 17.2, 10.4 Hz, 1H), 6.27 (dd, J = 17.4, 2.0 Hz, 1H), 5.78 (dd, J = 10.4, 2.0 Hz, 1H), 3.80 (s, 3H), 2.41 (d, J = 2.4 Hz, 3H). 538 117 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; ¹ H NMR (400 MHz, DMSO) δ 10.25 (s, 1H), 8.18 (s, 1H), 7.75 (t, J = 7.7 Hz, 1H), 7.68 (d, J = 8.5 Hz, 2H), 7.33 ( s, 2H), 7.22 (d, J = 8.4 Hz, 2H), 7.11 (d, J = 8.6 Hz, 2H), 7.04 (d, J = 7.3 Hz, 1H), 6.79 (d, J = 8.1 Hz, 1H), 6.47 - 6.38 (m, 1H), 6.26 (m, 1H), 5.76 (m, 1H), 3.83 (s, 3H), 2.34 (s, 3H). 501 118 N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)-1-methyl Base-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.29 (s, 1H), 8.19 (s, 1H), 7.70 (d, J = 8.4 Hz, 2H), 7.62 (d, J = 2.4 Hz, 1H), 7.28 ( d, J = 8.4 Hz, 2H), 7.22 - 7.12 (m, 2H), 7.01 (dd, J = 8.4, 1.2 Hz, 1H), 6.44 (dd, J = 17.2, 10.0 Hz, 1H), 6.27 (dd , J = 17.2, 2.0 Hz, 1H), 5.86 (d, J = 2.4 Hz, 1H), 5.78 (dd, J = 10.0, 2.0 Hz, 1H), 3.79 (s, 3H), 3.72 (s, 3H) . 508 119 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; ¹ H NMR (400 MHz, DMSO) δ10.33 (s, 1H), 8.67 (d, J = 4.8 Hz, 2H), 8.36 (s, 1H), 7.75 (d, J = 8.4 Hz, 2H), 7.40 (t, J = 8.4 Hz, 1H), 7.36 - 7.31 (m, 3H), 7.28 (dd, J = 11.2, 2.0 Hz, 1H), 7.13 (dd, J = 8.4, 1.2 Hz, 1H), 6.44 ( dd, J = 18.0, 10.0 Hz, 1H), 6.28 (dd, J = 18.0, 2.0 Hz, 3H), 5.79 (dd, J = 10.0, 2.0 Hz, 1H), 3.83 (s, 3H). 506 120 N-(4-(4-amino-7-cyano-3-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl-1H- Pyrro[3,2-c]pyridin-2-yl)phenyl]acrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.31 (s, 1H), 8.87-8.86 (d, J = 4.0 Hz, 1H), 8.37 (s, 1H), 7.74-7.71 (d, J = 12.0 Hz, 2H ), 7.56-7.54 (d, J = 8.0 Hz, 1H), 7.35-7.28 (m, 6H), 7.05-6.78(m, 1H), 6.47-6.40 (m, 1H), 6.30-6.25 (m, 1H ), 5.80-5.77 (m, 1H), 3.85 (s, 3H). 538 121 N-(4-(4-amino-7-cyano-1-methyl-3-(4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)-1H- Pyrro[3,2-c]pyridin-2-yl)phenyl)acrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.27 (s, 1H), 8.18 (s, 1H), 7.68 (d, J = 8.5 Hz, 2H), 7.65 (d, J = 2.3 Hz, 1H), 7.26 ( d, J = 8.6 Hz, 2H), 7.21 (d, J = 8.7 Hz, 2H), 7.03 (d, J = 8.6 Hz, 2H), 6.41 (d, J = 10.1 Hz, 1H), 6.29 (d, J = 1.9 Hz, 1H), 5.88 (d, J = 2.3 Hz, 1H), 5.77 (dd, J = 10.0, 2.0 Hz, 1H), 3.80 (s, 3H), 3.74 (s, 3H). 490 122 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; ¹ H NMR (400 MHz, DMSO) δ 10.13 (s, 1H), 8.88 - 8.67 (m, 2H), 8.21 (s, 1H), 7.77 (m, 1H), 7.51 (m, 1H), 7.36 - 7.26 (m, 3H), 7.23 (m, 2H), 5.81 (s, 1H), 5.58 (s, 1H), 3.75 (s, 3H), 1.94 (s, 3H). 538 123 N-(4-(4-amino-7-cyano-3-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)-3-fluorophenyl)-1-methyl Base-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.14 (s, 1H), 8.89 (d, J = 4.8 Hz, 1H), 8.23 (s, 1H), 7.79 (dd, J = 12.4, 1.6 Hz, 1H), 7.59 (d, J = 5.2 Hz, 1H), 7.54 (dd, J = 8.4, 2.0 Hz, 1H), 7.44 (t, J = 8.4 Hz, 1H), 7.34 (t, J = 8.4 Hz, 1H), 7.27 (d, J = 11.2 Hz, 1H), 7.13 (d, J = 8.4 Hz, 1H), 6.92 (t, J = 54.0 Hz, 1H), 5.82 (s, 1H), 5.58 (s, 1H), 3.76 (s, 3H), 1.95 (s, 3H). 588 124 N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl Base-1H-pyrrole[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.14 (s, 1H), 8.56 (d, J = 1.2 Hz, 1H), 8.23 (s, 1H), 7.78 (dd, J = 12.4, 2.0 Hz, 1H), 7.53 (dd, J = 8.4, 2.0 Hz, 1H), 7.40 - 7.30 (m, 2H), 7.24 (d, J = 10.8 Hz, 1H), 7.10 (d, J = 8.4 Hz, 1H), 5.82 (s , 1H), 5.58 (s, 1H), 3.75 (s, 3H), 2.40 (d, J = 2.4 Hz, 3H), 1.95 (s, 3H). 570 125 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; ¹ H NMR (400 MHz, DMSO) δ 10.15 (s, 1H), 8.68 (d, J = 4.8 Hz, 2H), 8.23 (s, 1H), 7.79 (dd, J = 12.4, 1.6 Hz, 1H), 7.54 (dd, J = 8.4, 2.0 Hz, 1H), 7.44 - 7.29 (m, 3H), 7.25 (d, J = 11.2 Hz, 1H), 7.12 (d, J = 8.4 Hz, 1H), 5.83 (s , 1H), 5.58 (s, 1H), 3.75 (s, 3H), 1.95 (s, 3H). 538 126 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; ¹ H NMR (400 MHz, DMSO) δ 10.13 (s, 1H), 8.50 (d, J = 5.2 Hz, 1H), 8.23 (s, 1H), 7.78 (m, 1H), 7.53 (m, 1H), 7.35 (m, 2H), 7.22 (m, 1H), 7.18 (d, J = 5.2 Hz, 1H), 7.10 (m, 1H), 5.81 (s, 1H), 5.58 (s, 1H), 3.76 (s , 3H), 2.68 (m, 3H), 1.95 (s, 3H), 1.12 (m, 3H). 566 127 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; ¹ H NMR (400 MHz, DMSO) δ 10.16 (s, 1H), 8.36 (s, 1H), 7.79 (dd, J = 12.4, 1.6 Hz, 1H), 7.76 - 7.71 (m, 1H), 7.54 (dd , J = 8.4, 1.6 Hz, 1H), 7.30 (dt, J = 10.8, 8.4 Hz, 2H), 7.21 (d, J = 10.4 Hz, 1H), 7.06 (d, J = 8.0 Hz, 1H), 7.00 (d, J = 7.2 Hz, 1H), 6.86 (d, J = 8.4 Hz, 1H), 5.81 (s, 1H), 5.58 (s, 1H), 3.81 (s, 3H), 2.27 (s, 3H) , 1.95 (s, 3H). 551 128 N-(4-(4-amino-7-cyano-3-(3-fluoro-4-(pyridin-2-yloxy)phenyl)-1-methyl-1H-pyrrole[3,2- c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.14 (s, 1H), 8.23 (s, 1H), 8.14 (m, 1H), 7.93 - 7.83 (m, 1H), 7.79 (dd, J = 12.4, 1.9 Hz , 1H), 7.53 (m, 1H), 7.32 (m, 2H), 7.21 (d, J = 11.2Hz, 1H), 7.18 - 7.06 (m, 3H), 5.82 (s, 1H), 5.58 (s, 1H), 3.75 (s, 3H), 1.95 (s, 3H). 537 129 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; ¹ H NMR (400 MHz, DMSO) δ 10.12 (s, 1H), 8.46-8.45 (d, J = 4.0 Hz, 1H), 8.21 (s, 1H), 7.79-7.75 (m, 1H), 7.52-7.49 (m, 1H), 7.32-7.28 (t, J = 8.0 Hz, 3H), 7.21-7.18 (d, J = 12.0 Hz, 2H), 7.15-7.14 (d, J = 4.0 Hz, 1H), 5.81 ( s, 1H), 5.57 (s, 1H), 3.75 (s, 3H), 2.40 (s, 3H), 1.94 (s, 3H). 534 130 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; ¹ H NMR (400 MHz, DMSO) δ 10.12 (s, 1H), 8.20 (s, 1H), 7.79 - 7.70 (m, 2H), 7.50 (m, 1H), 7.27 (m, 3H), 7.09 (d , J = 8.7 Hz, 2H), 7.01 (d, J = 7.4 Hz, 1H), 6.79 (s, 1H), 5.81 (s, 1H), 5.57 (s, 1H), 3.76 (s, 3H), 2.32 (s, 3H), 1.94 (s, 3H). 533 131 N-(4-(4-amino-7-cyano-1-methyl-3-(4-(pyrimidin-2-yloxy)phenyl)-1H-pyrrolo[3,2-c]pyridine -2-yl)-3-fluorophenyl)methacrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.14 (s, 1H), 8.66 (d, J = 4.8 Hz, 2H), 8.21 (s, 1H), 7.78 (dd, J = 12.4, 2.0 Hz, 1H), 7.51 (m, 1H), 7.34 - 7.27 (m, 4H), 7.24 -7.22 (m, 2H), 5.82 (s, 1H), 5.58 (s, 1H), 3.75 (s, 3H), 1.94 (s, 3H). 520 132 4-(4-amino-7-cyano-2-(2-fluoro-4-methacrylamidephenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridine-3- methyl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide ¹ H NMR (400 MHz, DMSO) δ 10.12 (s, 1H), 8.65 (t, J = 12.8 Hz, 1H), 8.23 (s, 1H), 7.76 (d, J = 10.0 Hz, 1H), 7.69 ( d, J = 7.6 Hz, 1H), 7.50 (d, J = 8.0 Hz, 1H), 7.31 (t, J = 16.8 Hz, 1H), 6.97 (s, 1H), 6.89 (d, J = 7.6 Hz, 1H), 5.82 (s, 1H), 5.58 (s, 1H), 4.08 (m, 2H), 3.76 (d, J = 2.8 Hz, 6H), 1.94 (s, 3H). 581 133 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; ¹ H NMR (400 MHz, DMSO) δ 10.15 (s, 1H), 8.46 (d, J = 4.8 Hz, 1H), 8.23 (s, 1H), 7.79 (d, J = 12.4 Hz, 1H), 7.54 ( d, J = 8.4 Hz, 1H), 7.43 (s, 1H), 7.35 (t, J = 18.0 Hz, 2H), 7.25 (d, J = 7.6 Hz, 1H), 7.17 (d, J = 4.8 Hz, 1H), 5.82 (s, 1H), 5.58 (s, 1H), 3.75 (s, 3H), 2.40 (s, 3H), 1.95 (s, 3H). 568 134 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; ¹ H NMR (400 MHz, DMSO-d6) δ 10.13 (s, 1H), 8.43 (d, J = 5.0 Hz, 1H), 8.21 (s, 1H), 7.78 (dd, J = 12.3, 1.8 Hz, 1H ), 7.51 (dd, J = 8.5, 1.8 Hz, 1H), 7.33 (d, J = 8.5 Hz, 1H), 7.22 (s, 1H), 7.17 - 7.04 (m, 3H), 5.81 (s, 1H) , 5.58 (s, 1H), 3.74 (s, 3H), 2.39 (s, 3H), 2.03 (s, 3H), 1.94 (s, 3H). 548 135 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; ¹ H NMR (400 MHz, DMSO) δ 10.11 (s, 1H), 8.46 (d, J = 5.0 Hz, 1H), 8.31 (s, 1H), 8.05 (s, 1H), 7.71 (d, J = 8.6 Hz, 1H), 7.42 - 7.31 (m, 2H), 7.19 (t, J = 11.3 Hz, 2H), 7.09 (s, 1H), 5.83 (s, 1H), 5.58 (s, 1H), 3.71 (s , 3H), 2.39 (s, 3H), 1.94 (s, 3H). 568 136 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; ¹ H NMR (400 MHz, DMSO) δ 10.17 (s, 1H), 8.50 (d, J = 5.2 Hz, 1H), 8.24 (s, 1H), 7.80 (d, J = 12.4 Hz, 1H), 7.57 ( d, J = 8.4 Hz, 1H), 7.36 (t, J = 8.4 Hz, 1H), 7.24 (d, J = 5.2 Hz, 1H), 7.10 (d, J = 8.4 Hz, 2H), 5.83 (s, 1H), 5.59 (s, 1H), 3.75 (s, 3H), 2.42 (s, 3H), 1.95 (s, 3H). 570 137 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; ¹ H NMR (400 MHz, DMSO) δ 10.15 (s, 1H), 8.28 (s, 1H), 8.23 (s, 1H), 7.79 (m, 1H), 7.54 (m, 1H), 7.33 (m, 2H ), 7.21 (d, J = 11.2 Hz, 1H), 7.09 (d, J = 8.0 Hz, 1H), 5.82 (s, 1H), 5.58 (s, 1H), 3.75 (s, 3H), 2.35 (s , 3H), 2.16 (s, 3H), 1.95 (s, 3H). 566 138 N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((5-fluoropyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrole And[3,2-c]pyridin-2-yl)phenyl)acrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.31 (s, 1H), 8.77 (s, 2H), 8.21 (s, 1H), 7.74-7.72 (d, J = 8.0 Hz, 2H), 7.40-7.38 (t , J = 8.0 Hz, 1H), 7.34-7.32 (d, J = 8.0 Hz, 2H), 7.28-7.25 (m, 1H), 7.15-7.13 (d, J = 8.0 Hz, 1H), 6.48-6.41 ( m, 1H), 6.30-6.25 (m, 1H), 5.80-5.77 (m, 1H), 3.79 (s, 3H). 524 139 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; ¹ H NMR (400 MHz, DMSO) δ 10.30 (s, 1H), 8.21 (s, 1H), 8.13 (m, 1H), 7.95 - 7.83 (m, 1H), 7.72 (m, 2H), 7.31 (t , J = 18 Hz, 3H), 7.22 (m, 2H), 7.18 - 7.05 (m, 1H), 6.44 (m, 1H), 6.27 (m, 1H), 5.78 (m, 1H), 3.79 (s, 3H). 505 140 N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((5-fluoropyridin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrole And[3,2-c]pyridin-2-yl]phenyl)acrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.31 (s, 1H), 8.20 (d, J = 2.0 Hz, 1H), 8.15 (d, J = 3.1 Hz, 1H), 7.86 (dd, J = 9.6, 7.3 Hz, 1H), 7.72 (d, J = 8.5 Hz, 2H), 7.31 (dd, J = 8.4, 6.8 Hz, 4H), 7.21 (dd, J = 9.0, 3.6 Hz, 3H), 7.10 (d, J = 9.8 Hz, 1H), 6.42 (d, J = 10.1 Hz, 1H), 6.30 (d, J = 1.9 Hz, 1H), 5.78 (dd, J = 10.1, 1.9 Hz, 1H), 3.79 (s, 3H ). 523 141 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; ¹ H NMR (400 MHz, DMSO) δ 10.30 (s, 1H), 8.29 (s, 1H), 8.21 (s, 1H), 7.73 (d, J = 8.4 Hz, 2H), 7.33 (m, 3H), 7.23 (m, 1H), 7.11 (m, 1H), 6.44 (m, 1H), 6.28 (m, 1H), 5.78 (m, 1H), 3.80 (s, 3H), 2.35 (s, 3H), 2.16 (s, 3H). 534 142 N-(4-(4-amino-7-cyano-3-(4-(cyclohexyloxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2- methyl)-3-fluorophenyl)methacrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.11 (s, 1H), 8.20 (d, J = 14.8 Hz, 2H), 7.74 (d, J = 11.2 Hz, 1H), 7.47 (d, J = 8.4 Hz, 1H), 7.25 (t, J = 16.8 Hz, 1H), 7.11 (s, 1H), 6.91 (d, J = 8.4 Hz, 2H), 5.81 (s, 1H), 5.57 (s, 1H), 4.31 ( s, 1H), 3.73 (s, 3H), 1.94 (s, 5H), 1.71 (s, 2H), 1.61 - 1.13 (m, 6H). 524 143 4-(4-Amino-7-cyano-2-(2-fluoro-4-methacrylamidephenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridine-3 -yl)-2-methoxy-N-(1-(trifluoromethyl)cyclopropyl)benzamide; ¹ H NMR (400 MHz, DMSO) δ 10.14 (s, 1H), 8.68 (s, 1H), 8.39 (s, 1H), 7.78-7.75 (m, 1H), 7.60-7.58 (d, J = 8.0 Hz , 1H), 7.53-7.50 (m, 1H), 7.33-7.29 (t, J = 8.0 Hz, 1H), 6.96 (s, 1H), 6.87-6.85 (d, J = 8.0 Hz, 1H), 5.82 ( s, 1H), 5.58 (s, 1H), 3.80 (s, 3H), 3.74 (s, 3H), 1.94 (s, 3H), 1.31-1.27 (m, 2H), 1.13 (s, 2H). 607 144 N-(4-(4-amino-7-cyano-1-methyl-3-(4-(pyridin-2-yloxy)phenyl)-1H-pyrrolo[3,2-c]pyridine -2-yl)-3-fluorophenyl)methacrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.12 (s, 1H), 8.21 (s, 1H), 8.19 (m, 1H), 7.87 (m, 1H), 7.77 (dd, J = 12.4, 2.0 Hz, 1H ), 7.50 (m, 1H), 7.28 (m, 3H), 7.18 - 7.10 (m, 3H), 7.05 (d, J = 8.4 Hz, 1H), 5.81 (s, 1H), 5.58 (s, 1H) , 3.75 (s, 3H), 1.94 (s, 3H). 519 145 N-(4-(4-amino-7-cyano-1-methyl-3-(4-(pyridin-2-yloxy)phenyl)-1H-pyrrolo[3,2-c]pyridine -2-yl)phenyl]acrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.28 (s, 1H), 8.20 - 8.17 (m, 2H), 7.92 - 7.81 (m, 1H), 7.70 (d, J = 8.4 Hz, 2H), 7.29 (m , 4H), 7.20 - 7.10 (m, 3H), 7.04 (m, 1H), 6.43 (m, 1H), 6.27 (m, 1H), 5.78 (m, 1H), 3.80 (s, 3H). 487 146 N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((5-fluoropyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrole And[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.17 (s, 1H), 8.77 (s, 2H), 8.34 (s, 1H), 7.82-7.78 (m, 1H), 7.56-7.54 (m, 1H), 7.44 -7.39 (t, J = 8.0 Hz, 1H), 7.37-7.33 (t, J = 8.0 Hz, 1H), 7.28-7.25 (d, J = 12.0 Hz, 1H), 7.12-7.10 (d, J = 8.0 Hz, 1H), 5.83 (s, 1H), 5.59 (s, 1H), 3.78 (s, 3H), 1.95 (s, 3H). 556 147 N-(4-(4-amino-3-(3-chloro-4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl Base-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.32 (s, 1H), 8.55 (s, 1H), 8.21 (s, 1H), 7.73 (d, J = 8.4 Hz, 2H), 7.44 (s, 1H), 7.31 (m, 4H), 6.44 (m, 1H), 6.27 (d, J = 17.2 Hz, 1H), 5.78 (d, J = 10 Hz, 1H), 3.79 (s, 3H), 2.41 (s, 3H ). 554 148 N-(4-(4-amino-3-(4-((6-chloropyridin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl-1H-pyrrole And[3,2-c]pyridin-2-yl]-3-fluorophenyl]methacrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.14 (s, 1H), 8.23 (s, 1H), 7.99 - 7.87 (m, 1H), 7.84 - 7.67 (m, 1H), 7.57 - 7.48 (m, 1H) , 7.39 - 7.18 (m, 4H), 7.16 - 7.05 (m, 2H), 5.81 (s, 1H), 5.58 (s, 1H), 3.77 (s, 3H), 1.94 (s, 3H). 571 149 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; ¹ H NMR (400 MHz, DMSO) δ 10.14 (s, 1H), 8.49 (s, 1H), 8.23 (s, 1H), 7.79 (d, J = 12.8 Hz, 1H), 7.59 - 7.06 (m, 5H ), 6.18 (s, 2H), 5.82 (s, 1H), 5.58 (s, 1H), 3.78 (s, 3H), 2.41 (s, 3H), 1.95 (s, 3H). 570 150 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; ¹ H NMR (400 MHz, DMSO) δ 10.15 (s, 1H), 8.50 (d, J = 5.0 Hz, 1H), 8.23 (s, 1H), 7.78 (dd, J = 12.8, 4.4 Hz, 1H), 7.53 (dd, J = 8.4, 1.8 Hz, 1H), 7.30 - 6.96 (m, 4H), 6.21 (s, 2H), 5.81 (s, 1H), 5.58 (s, 1H), 3.79 (d, J = 4.8 Hz, 3H), 2.41 (s, 3H), 1.95 (s, 3H). 570 151 N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H- Pyrro[3,2-c]pyridin-2-yl)-2-fluoro-3-methylphenyl)methacrylamide; ¹ H NMR (400 MHz, DMSO) δ 9.60 (s, 1H), 8.46 (d, J = 5.2 Hz, 1H), 8.36 (s, 1H), 7.57 (t, J = 8.0 Hz, 1H), 7.35 ( t, J = 8.4 Hz, 1H), 7.24 - 7.20 (m, 1H), 7.18 (d, J = 5.2 Hz, 2H), 7.07 (d, J = 8.4 Hz, 1H), 5.87 (s, 1H), 5.56 (s, 1H), 3.71 (s, 3H), 2.39 (s, 3H), 1.96 - 1.91 (m, 6H). 566 152 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; ¹ H NMR (400 MHz, DMSO) δ 10.12 (s, 1H), 8.49 (d, J = 5.0 Hz, 1H), 8.22 (s, 1H), 7.76 (d, J = 11.8 Hz, 1H), 7.50 ( d, J = 8.1 Hz, 1H), 7.43 (s, 1H), 7.25 -7.18 (m, 3H), 7.12 - 7.03 (m, 1H), 5.81 (s, 1H), 5.57 (s, 1H), 3.79 (s, 3H), 2.41 (s, 3H), 1.94 (s, 3H). 552 153 N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((5-fluoropyridin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrole And[3,2-c]pyridin-2-yl]-3-fluorophenyl)methacrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.15 (s, 1H), 8.23 (s, 1H), 8.15 (d, J = 3.1 Hz, 1H), 7.89 - 7.82 (m, 1H), 7.79 (dd, J = 12.4, 1.9 Hz, 1H), 7.52 (d, J = 1.9 Hz, 1H), 7.32 (d, J = 6.0 Hz, 2H), 7.21 (dd, J = 9.1, 3.5 Hz, 2H), 7.09 (d , J = 7.9 Hz, 1H), 5.82 (s, 1H), 5.59 (s, 1H), 3.75 (s, 3H), 1.95 (s, 3H). 555 154 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; ¹ H NMR (400 MHz, DMSO) δ 10.31 (s, 1H), 8.37 (s, 1H), 8.20 (d, J = 3.2 Hz, 1H), 7.85 (ddd, J = 9.2, 8.0, 3.2 Hz, 1H ), 7.72 (d, J = 8.8 Hz, 2H), 7.38 - 7.24 (m, 4H), 7.15 (dd, J = 5.6, 3.2 Hz, 3H), 6.44 (dd, J = 17.2, 10.0 Hz, 1H) , 6.27 (dd, J = 17.2, 2.0 Hz, 1H), 5.79 (dd, J = 10.0, 2.0 Hz, 1H), 3.85 (s, 3H). 505 155 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; ¹ H NMR (400 MHz, DMSO) δ 10.29 (s, 1H), 8.52 (d, J = 1.2 Hz, 1H), 8.19 (s, 1H), 7.72-7.70 (d, J = 8.0 Hz, 2H), 7.33-7.31 (d, J = 8.0 Hz, 2H), 7.24 (s, 1H), 7.14 - 7.09 (m, 2H), 6.47-6.40 (m, 1H), 6.29-6.25 (m, 1H), 5.79- 5.76 (m, 1H), 3.80 (s, 3H), 2.40 (d, J = 2.4 Hz, 3H), 2.05 (s, 3H). 534 156 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; ¹ H NMR (400 MHz, DMSO) δ 10.34 (s, 1H), 8.59 (s, 1H), 8.35 (s, 1H), 7.76 (d, J = 8.4 Hz, 2H), 7.33 (d, J = 8.4 Hz, 2H), 7.14 (d, J = 8.4 Hz, 2H), 6.45 (dd, J = 16.8, 10.4 Hz, 1H), 6.28 (d, J = 19.2 Hz, 1H), 5.79 (d, J = 11.6 Hz, 1H), 3.82 (s, 3H), 2.42 (d, J = 2.4 Hz, 3H). 556 157 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; ¹ H NMR (400 MHz, DMSO) δ 10.51 (s, 1H), 8.55 (d, J = 1.2 Hz, 1H), 8.21 (s, 1H), 7.78 (dd, J = 12.0, 1.6 Hz, 1H), 7.39 (dd, J = 8.4, 2.0 Hz, 1H), 7.34 - 7.28 (m, 3H), 7.20 (d, J = 8.8 Hz, 2H), 6.42 (dd, J = 17.2, 10.0 Hz, 1H), 6.30 (dd, J = 17.2, 2.0 Hz, 1H), 5.82 (dd, J = 10.0, 2.0 Hz, 1H), 3.75 (s, 3H), 2.40 (d, J = 2.4 Hz, 3H). 538 158 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; ¹ H NMR (400 MHz, DMSO) δ 10.11 (s, 1H), 8.19 (s, 1H), 7.75 (m, 1H), 7.65 (d, J = 2.3 Hz, 1H), 7.48 (m, 1H), 7.25 (t, J = 8.4 Hz, 1H), 7.20 (d, J = 7.4 Hz, 2H), 7.03 (d, J = 8.8 Hz, 2H), 5.89 (d, J = 2.3 Hz, 1H), 5.81 ( s, 1H), 5.57 (s, 1H), 3.74 (s, 6H), 1.94 (s, 3H). 522 159 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; ¹ H NMR (400 MHz, DMSO) δ 10.13 (s, 1H), 8.29 - 8.09 (m, 2H), 7.89 - 7.80 (m, 1H), 7.79 - 7.70 (m, 1H), 7.53 - 7.46 (m, 1H), 7.33 - 7.18 (m, 3H), 7.17 - 7.05 (m, 3H), 5.81 (s, 1H), 5.58 (s, 1H), 3.75 (s, 3H), 1.94 (s, 3H). 537 160 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; ¹ H NMR (400 MHz, DMSO) δ 10.31 (s, 1H), 8.59 (d, J = 1.1 Hz, 1H), 8.21 (s, 1H), 7.73 (d, J = 8.6 Hz, 2H), 7.28 ( d, J = 8.6 Hz, 2H), 7.22 (dd, J = 15.2, 7.6 Hz, 2H), 6.48 - 6.40 (m, 1H), 6.28 (dd, J = 17.0, 1.9 Hz, 1H), 6.11 (s , 2H), 5.79 (dd, J = 10.1, 1.9 Hz, 1H), 3.84 (s, 3H), 2.42 (s, 3H). 556 161 N-(4-(4-amino-7-cyano-3-(4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H- Pyrro[3,2-c]pyridin-2-yl)-3-methylphenyl)acrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.22 (s, 1H), 8.54 (d, J = 1.3 Hz, 1H), 8.19 (s, 1H), 7.57 (dd, J = 15.2, 6.6 Hz, 2H), 7.32 - 7.11 (m, 5H), 6.43 (m, 1H), 6.26 (m, 1H), 5.77 (m, 1H), 3.64 (s, 3H), 2.39 (d, J = 2.5 Hz, 3H), 1.99 (s, 3H). 534 162 N-(4-(4-amino-7-cyano-3-(4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H- Pyrro[3,2-c]pyridin-2-yl)-3-chlorophenyl)acrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.47 (s, 1H), 8.54 (d, J = 1.3 Hz, 1H), 8.22 (s, 1H), 8.04 (d, J = 2.0 Hz, 1H), 7.56 ( dd, J = 8.4, 2.0 Hz, 1H), 7.39 (d, J = 8.4 Hz, 1H), 7.29 (d, J = 7.4 Hz, 2H), 7.19 (d, J = 8.8 Hz, 2H), 6.42 ( dd, J = 17.0, 10.0 Hz, 1H), 6.30 (dd, J = 17.0, 2.0 Hz, 1H), 5.82 (dd, J = 10.0, 2.0 Hz, 1H), 3.69 (s, 3H), 2.39 (d , J = 2.5 Hz, 3H). 554 163 N-(4-(4-amino-7-cyano-3-(4-(cyclohexyloxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2- Base) benzene) acrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.28 (s, 1H), 8.35 (s, 1H), 7.69 (d, J = 8.0 Hz, 2H), 7.27 (d, J = 8.4 Hz, 2H), 7.14 ( d, J = 8.4 Hz, 2H), 6.93 (d, J = 8.0 Hz, 2H), 6.43 (dd, J = 16.8, 10.4 Hz, 1H), 6.26 (d, J = 15.2 Hz, 1H), 5.78 ( d, J = 11.6 Hz, 1H), 4.32 (m, 1H), 3.83 (s, 3H), 1.91 (s, 2H), 1.71 (s, 2H), 1.52 (s, 1H), 1.38 (d, J = 9.6 Hz, 4H), 1.23 (s, 1H). 492 164 N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl Base-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.34 (s, 1H), 8.63 (s, 1H), 8.42 (s, 1H), 7.76-7.74 (d, J = 8.0 Hz, 2H), 7.42-7.38 (t , J = 8.0 Hz, 1H), 7.33-7.31 (d, J = 8.0 Hz, 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). 554 165 N-(4-(4-amino-7-cyano-3-(4-(cyclohexanecarbonyl)-3-fluorophenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridine -2-yl)phenyl)acrylamide ¹ H NMR (400 MHz, DMSO) δ 10.30 (s, 1H), 8.22 (s, 1H), 7.70 (m, 3H), 7.27 (d, J = 8.4 Hz, 2H), 7.15 - 7.09 (m, 2H ), 6.43 (m, 1H), 6.27 (m, 1H), 5.78 (m, 1H), 3.79 (s, 3H), 3.09 (s, 1H), 1.83 (m, 4H), 1.72 (m, 2H) , 1.27 (m, 4H). 522 166 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; ¹ H NMR (400 MHz, DMSO) δ 10.30 (s, 1H), 8.21 (s, 1H), 7.78 - 7.65 (m, 2H), 7.54 - 7.46 (m, 1H), 7.33 - 7.27 (m, 3H) , 7.27 - 7.22 (m, 2H), 7.16 - 7.07 (m, 1H), 6.49 - 6.37 (m, 1H), 6.31 - 6.22 (m, 1H), 6.07 (s, 2H), 5.83 - 5.72 (m, 1H), 3.80 (s, 3H). 511 167 N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((4-methylthiazol-2-yl)oxy)phenyl)-1-methyl-1H- Pyrro[3,2-c]pyridin-2-yl)phenyl)acrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.32 (s, 1H), 8.35 (s, 1H), 7.73 (d, J = 8.4 Hz, 2H), 7.51 (t, J = 8.4 Hz, 1H), 7.31 ( dd, J = 13.2, 5.2 Hz, 3H), 7.11 (dd, J = 8.4, 1.0 Hz, 1H), 6.81 (d, J = 1.2 Hz, 1H), 6.44 (dd, J = 17.2, 10.0 Hz, 1H ), 6.27 (dd, J = 17.2, 2.0 Hz, 1H), 5.78 (dd, J = 10.0, 2.0 Hz, 1H), 3.84 (s, 3H), 2.18 (d, J = 1.2 Hz, 3H). 525 168 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; ¹ H NMR (400 MHz, DMSO) δ 10.33 (s, 1H), 9.04 (d, J = 4.8 Hz, 1H), 8.39 (s, 1H), 7.85 (d, J = 4.8 Hz, 1H), 7.74 ( d, J = 8.4 Hz, 2H), 7.48 (t, J = 8.4 Hz, 1H), 7.32 (d, J = 8.8 Hz, 3H), 7.15 (d, J = 8.4 Hz, 1H), 6.44 (dd, J = 17.2, 10.1 Hz, 1H), 6.28 (dd, J = 16.8, 1.6 Hz, 1H), 5.79 (dd, J = 10.0, 1.6 Hz, 1H), 3.85 (s, 3H). 574 169 N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((4-(trifluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl Base-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorophenyl)methacrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.14 (s, 1H), 9.04 (d, J = 4.8 Hz, 1H), 8.23 (s, 1H), 7.84 (d, J = 5.2 Hz, 1H), 7.78 ( dd, J = 12.4, 2.0 Hz, 1H), 7.53 (dd, J = 8.4, 2.0 Hz, 1H), 7.47 (t, J = 8.4 Hz, 1H), 7.33 (t, J = 8.4 Hz, 1H), 7.28 (d, J = 11.2 Hz, 1H), 7.14 (d, J = 8.0 Hz, 1H), 5.81 (s, 1H), 5.58 (s, 1H), 3.76 (s, 3H), 1.95 (s, 3H ). 606 170 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; ¹ H NMR (400 MHz, DMSO) δ 9.90 (s, 1H), 8.47 (d, J = 4.8 Hz, 1H), 8.25 (s, 1H), 7.47 (t, J = 7.2 Hz, 1H), 7.38 ( t, J = 8.4 Hz, 1H), 7.28 - 7.16 (m, 3H), 7.12 (d, J = 8.0 Hz, 1H), 6.17 (br, 2H), 5.89 (s, 1H), 5.60 (s, 1H ), 3.80 (s, 3H), 2.40 (s, 3H), 1.95 (s, 3H). 570 171 N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((5-fluoro-6-methylpyridin-2-yl)oxy)phenyl)-1-methyl Base-1H-pyrrolo[3,2-c]pyridin-2-yl]-3-fluorophenyl)methacrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.16 (s, 1H), 8.39 (s, 1H), 7.83 - 7.66 (m, 2H), 7.55 (d, J = 8.4 Hz, 1H), 7.29 (dt, J = 11.6, 8.4 Hz, 2H), 7.22 (d, J = 11.2 Hz, 1H), 7.08 - 6.91 (m, 2H), 5.81 (s, 1H), 5.59 (s, 1H), 3.81 (s, 3H) , 2.24 (d, J = 3.2 Hz, 3H), 1.95 (s, 3H). 569 172 N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((5-fluoro-6-methylpyridin-2-yl)oxy)phenyl)-1-methyl Base-1H-pyrrolo[3,2-c]pyridin-2-yl]phenyl)acrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.32 (s, 1H), 8.39 (s, 1H), 7.73 (dd, J = 8.0, 3.2 Hz, 3H), 7.28 (dd, J = 13.2, 8.4 Hz, 4H ), 7.07 (d, J = 8.0 Hz, 1H), 6.97 (dd, J = 8.8, 2.8 Hz, 1H), 6.44 (dd, J = 17.2, 10.0 Hz, 1H), 6.28 (dd, J = 17.2, 2.0 Hz, 1H), 5.79 (dd, J = 10.0, 2.0 Hz, 1H), 3.87 (s, 3H), 2.25 (d, J = 2.8 Hz, 3H). 537 173 N-(4-(4-amino-7-cyano-3-(4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H- Pyrro[3,2-c]pyridin-2-yl)-2,3-difluorophenyl)acrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.28 (s, 1H), 8.55 (s, 1H), 8.23 (s, 1H), 7.94 (t, J = 7.6 Hz, 1H), 7.31 (d, J = 8.3 Hz, 2H), 7.21 (t, J = 8.9 Hz, 3H), 6.64 (dd, J = 17.0, 10.2 Hz, 1H), 6.31 (dd, J = 17.0, 1.7 Hz, 1H), 5.87 - 5.78 (m , 1H), 3.79 (s, 3H), 2.40 (d, J = 2.4 Hz, 3H). 556 174 N-(4-(4-amino-7-cyano-3-(4-(cyclohexyloxy)-3-fluorophenyl)-1-methyl-1H-pyrrolo[3,2-c] Pyridin-2-yl)-3-fluorophenyl)methacrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.11 (s, 1H), 8.19 (s, 1H), 7.75 (dd, J = 12.4, 1.5 Hz, 1H), 7.49 (dd, J = 8.4, 1.6 Hz, 1H ), 7.33 - 6.85 (m, 4H), 6.05 (s, 1H), 5.81 (s, 1H), 5.58 (s, 1H), 4.46 - 4.26 (m, 1H), 3.73 (s, 3H), 1.93 ( d, J = 14.8 Hz, 5H), 1.70 (d, J = 5.2 Hz, 2H), 1.56 - 0.93 (m, 6). 542 175 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; ¹ H NMR (400 MHz, DMSO) δ 10.28 (s, 1H), 8.19 (s, 1H), 7.71-7.69 (d, J = 8.0 Hz, 2H), 7.29-7.26 (d, J = 12.0 Hz, 2H ), 7.19-7.13 (m, 2H), 7.01-6.99 (m, 1H), 6.47-6.40 (m, 1H), 6.29-6.25 (m, 1H), 5.79-5.76 (m, 1H), 5.67 (s , 1H), 3.79 (s, 3H), 3.59 (s, 3H), 2.20 (s, 3H). 522 176 N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((1-methyl-5-(trifluoromethyl))-1H-pyrazol-3-yl)oxy base)phenyl)-1-methyl-1H-pyrrole[3,2-c]pyridin-2-yl)phenyl)acrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.29 (s, 1H), 8.20 (s, 1H), 7.71 (d, J = 8.4 Hz, 2H), 7.30 - 7.19 (m, 4H), 7.03 (d, J = 8.4 Hz, 1H), 6.65 (s, 1H), 6.43 (dd, J = 17.2, 10.0 Hz, 1H), 6.27 (dd, J = 17.2, 2.0 Hz, 1H), 5.78 (dd, J = 10.0, 2.0 Hz, 1H), 3.85 (s, 3H), 3.79 (s, 3H). 576 177 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; ¹ H NMR (400 MHz, DMSO) δ 10.26 (s, 1H), 8.18 (s, 1H), 7.68 (d, J = 8.4 Hz, 2H), 7.26 (t, J = 8.4 Hz, 4H), 7.09 ( d, J = 8.4 Hz, 2H), 6.67 (s, 1H), 6.43 (dd, J = 17.2, 10.0 Hz, 1H), 6.26 (dd, J = 17.2, 2.0Hz, 1H), 5.77 (dd, J = 10.0, 2.0 Hz, 1H), 3.87 (s, 3H), 3.80 (s, 3H). 558 178 N-(4-(4-amino-7-cyano-1-methyl-3-(4-(tetrafluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3 ,2-c]pyridin-2-yl)phenylacrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.28 (s, 1H), 9.00 (d, J = 4.8 Hz, 1H), 8.20 (s, 1H), 7.79 (d, J = 4.9 Hz, 1H), 7.70 ( d, J = 8.4 Hz, 2H), 7.36 - 7.29 (m, 6H), 6.49 - 6.38 (m, 1H), 6.27 (d, J = 15.9 Hz, 1H), 5.78 (d, J = 11.2 Hz, 1H ), 3.81 (s, 3H). 556 179 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; ¹ H NMR (400 MHz, DMSO) δ 10.13 (s, 1H), 9.00 (d, J = 4.9 Hz, 1H), 8.22 (s, 1H), 7.77 (m, 2H), 7.51 (m, 1H), 7.30 (m, 5H), 5.81 (s, 1H), 5.58 (s, 1H), 3.76 (s, 3H), 1.94 (s, 3H). 588 180 N-(4-(4-amino-7-cyano-3-(4-((4,6-dimethylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrole And[3,2-c]pyridin-2-yl)phenyl)acrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.26 (s, 1H), 8.19 (s, 1H), 7.70 (d, J = 8.4 Hz, 2H), 7.35 - 7.24 (m, 4H), 7.20 - 7.12 (m , 2H), 7.01 (s, 1H), 6.43 (dd, J = 16.8, 10.0 Hz, 1H), 6.26 (dd, J = 16.8, 2.0 Hz, 1H), 5.77 (dd, J = 10.0, 2.0 Hz, 1H), 3.82 (s, 3H), 2.32 (s, 6H). 516 181 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; ¹ H NMR (400 MHz, DMSO) δ 10.12 (s, 1H), 8.86 (d, J = 4.8 Hz, 1H), 8.21 (s, 1H), 7.77 (dd, J = 14.4,1.8 Hz, 1H), 7.61 - 7.43 (m, 2H), 7.30 (m, 5H), 6.91 (t, J = 108.4 Hz, 1H), 5.81 (s, 1H), 5.58 (s, 1H), 3.76 (s, 3H), 1.94 (s, 3H). 570 182 N-(4-(4-amino-7-cyano-3-(4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H- Pyrrole[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.08 (s, 1H), 8.54 (d, J = 1.0 Hz, 1H), 8.21 (s, 1H), 8.02 (d, J = 1.9 Hz, 1H), 7.67 ( m, 1H), 7.37 (d, J = 8.4 Hz, 1H), 7.29 (d, J = 7.6 Hz, 2H), 7.19 (d, J = 8.8 Hz, 2H), 5.82 (s, 1H), 5.58 ( s, 1H), 3.69 (s, 3H), 2.40 (d, J = 2.4 Hz, 3H), 1.94 (s, 3H). 568 183 N-(4-(4-amino-7-cyano-1-methyl-3-(4-((1-methyl-1H-pyrazol-5-yl)oxy)phenyl)-1H- Pyrro[3,2-c]pyridin-2-yl)phenyl)acrylamide; ¹ H NMR (400 MHz, DMSO) δ 10.27 (s, 1H), 8.18 (s, 1H), 7.68 (d, J = 8.0 Hz, 2H), 7.36 (d, J = 2.0 Hz, 1H), 7.29- 7.25 (m, 4H), 7.11 (d, J = 8.4 Hz, 2H), 6.43 (m, 1H), 6.27 (m, 1H), 5.78 (m, 2H), 3.80 (s, 3H), 3.64 (s , 3H). 490 184 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; ¹ H NMR (400 MHz, DMSO) δ 10.09 (s, 1H), 8.43-8.42 (d, J = 4.0 Hz, 1H), 8.21 (s, 1H), 8.03 (m, 1H), 7.70-7.67 (m , 1H), 7.41-7.39 (d, J = 8.0 Hz, 1H), 7.22 (s, 1H), 7.13 - 7.10 (m, 3H), 5.82 (s, 1H), 5.58 (s, 1H), 3.68 ( s, 3H), 2.39 (s, 3H), 2.03 (s, 3H), 1.94 (s, 3H). 564 185 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; ¹ H NMR (400 MHz, DMSO) δ 10.28 (s, 1H), 8.19 (s, 1H), 7.85 - 7.62 (m, 3H), 7.28 (d, J = 8.4 Hz, 2H), 7.22 - 7.13 (m , 2H), 7.01 (d, J = 8.4Hz, 1H), 6.43 (m, 1H), 6.27 (m, 1H), 5.85 (d, J = 2.4 Hz, 1H), 5.78 (m, 1H), 3.79 (s, 3H), 3.60 (m, 1H), 1.01 - 0.94 (m, 2H), 0.94 - 0.86 (m, 2H). 534 186 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; ¹ H NMR (400 MHz, DMSO) δ 10.14 (s, 1H), 8.45 (d, J = 4.8 Hz, 1H), 8.38 (s, 1H), 8.06 (d, J = 2.0 Hz, 1H), 7.73 ( m, 1H), 7.42 (d, J = 8.4 Hz, 2H), 7.36 (d, J = 8.4 Hz, 1H), 7.23 (d, J = 7.6 Hz, 1H), 7.17 (d, J = 5.2 Hz, 1H), 5.83 (s, 1H), 5.59 (s, 1H), 3.73 (s, 3H), 2.40 (s, 3H), 1.95 (s, 3H). 584 187 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; ¹ H NMR (400 MHz, DMSO) δ 10.10 (s, 1H), 8.45 - 8.27 (m, 1H), 8.03 (s, 1H), 7.76 - 7.64 (m, 2H), 7.34 (d, J = 8.4 Hz , 1H), 7.32 - 7.16 (m, 2H), 7.10 (d, J = 8.4 Hz, 2H), 7.02 (d, J = 7.6 Hz, 1H), 6.78 (d, J = 8.0 Hz, 1H), 5.82 (s, 1H), 5.58 (s, 1H), 3.74 (s, 3H), 2.32 (s, 3H), 1.94 (s, 3H). 549 188 N-(4-(4-amino-3-(3-chloro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H- Pyrro[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide; ¹ H NMR (400 MHz, DMSO) δ 9.86 (s, 1H), 8.45 (d, J = 5.2 Hz, 1H), 8.21 (s, 1H), 7.66 (s, 1H), 7.61 (d, J = 10 Hz, 1H), 7.39 (d, J = 1.6 Hz, 1H), 7.30 (dd, J = 19.6, 8.3 Hz, 2H), 7.23 (dd, J = 8.4, 1.6 Hz, 1H), 7.16 (d, J = 5.5 Hz, 1H), 6.08 (s, 2H), 5.80 (s, 1H), 5.53 (s, 1H), 3.64 (s, 3H), 2.40 (s, 3H), 1.96 (d, J = 14.8 Hz , 6H). 564 189 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; ¹ H NMR (400 MHz, DMSO-d6) δ 10.09 (s, 1H), 8.86 (d, J = 4.9 Hz, 1H), 8.22 (s, 1H), 8.03 (d, J = 1.9 Hz, 1H), 7.68 (dd, J = 8.4, 2.0 Hz, 1H), 7.55 (dd, J = 8.8, 5.1 Hz, 2H), 7.38 (d, J = 8.5 Hz, 1H), 7.36 – 7.23 (m, 2H), 6.91 (t, J = 54.0 Hz, 1H), 5.82 (s, 1H), 5.58 (s, 1H), 3.69 (s, 3H), 1.94 (s, 3H). 586 190 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; ¹ H NMR (400 MHz, DMSO-d6) δ 10.12 (s, 1H), 8.42 (s, 1H), 8.05 (s, 1H), 7.73 (t, J = 7.8 Hz, 1H), 7.37 (d, J = 8.4 Hz, 1H), 7.27 (t, J = 8.4 Hz, 1H), 7.20 (s, 1H), 7.02 (dd, J = 16.0, 8.0 Hz, 2H), 6.85 (d, J = 8.2 Hz, 1H ), 5.82 (s, 1H), 5.59 (s, 1H), 3.76 (s, 3H), 2.25 (s, 3H), 1.94 (s, 3H). 566 191 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; ¹ H NMR (400 MHz, DMSO-d6) δ 10.51 (s, 1H), 8.86 (d, J = 4.9 Hz, 1H), 8.21 (s, 1H), 7.79 (d, J = 12.1 Hz, 1H), 7.55 (s, 1H), 7.43 – 7.23 (m, 6H), 6.91 (t, J = 54.1 Hz, 1H), 6.42 (dd, J = 16.9, 9.9 Hz, 1H), 6.30 (dd, J = 16.9, 1.8 Hz, 1H), 5.82 (dd, J = 10.0, 1.8 Hz, 1H), 3.76 (s, 3H). 556 192 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; ¹ H NMR (400 MHz, DMSO-d6) δ 10.50 (s, 1H), 8.45 (d, J = 5.0 Hz, 1H), 8.21 (s, 1H), 7.79 (dd, J = 12.2, 1.7 Hz, 1H ), 7.39 (dd, J = 8.4, 1.8 Hz, 1H), 7.31 (dd, J = 15.8, 7.6 Hz, 3H), 7.20 (d, J = 8.7 Hz, 2H), 7.14 (d, J = 5.0 Hz , 1H), 6.42 (dd, J = 17.0, 10.0 Hz, 1H), 6.29 (dd, J = 17.0, 1.9 Hz, 1H), 5.82 (dd, J = 10.0, 1.9 Hz, 1H), 3.76 (s, 3H), 2.40 (s, 3H). 520 193 N-(4-(4-amino-7-cyano-3-(4-(cyclohexyloxy)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2- methyl)-3-chlorophenyl)methacrylamide. ¹ H NMR (400 MHz, DMSO-d6) δ 10.08 (s, 1H), 8.32 (s, 1H), 8.01 (s, 1H), 7.65 (d, J = 8.7 Hz, 1H), 7.31 (d, J = 8.4 Hz, 1H), 7.11 (m, 2H), 6.91 (d, J = 8.6 Hz, 2H), 5.82 (s, 1H), 5.58 (s, 1H), 4.30 (1, 1H), 3.71 (s , 3H), 1.94 (s, 3H), 1.91 (s, 2H), 1.70 (s, 2H), 1.51 (s, 1H), 1.45 – 1.28 (m, 4H), 1.24 (s, 1H). 540

Some compounds of the invention are listed in Table 3.

table 3 Compound serial number Name MW 194 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; 547 195 N-(4-(4-amino-7-cyano-3-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl-1H- Pyrro[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide; 566 196 N-(4-(4-amino-7-cyano-3-(4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H- Pyrrole[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide; 548 197 N-(4-(4-amino-7-cyano-1-methyl-3-(4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)-1H- Pyrro[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide; 518 198 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; 544 199 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; 529 200 N-(4-(4-amino-7-cyano-3-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)-3-fluorophenyl)-1-methyl Base-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; 604 201 N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl Base-1H-pyrrole[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; 586 202 N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((4-(trifluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl Base-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; 622 203 N-(4-(4-amino-7-cyano-1-methyl-3-(4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)-1H- Pyrro[3,2-c]pyridin-2-yl)-3-methylphenyl)-2-fluoroacrylamide; 522 204 N-(4-(4-amino-7-cyano-3-(4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H- Pyrro[3,2-c]pyridin-2-yl)-3-methylphenyl)-2-fluoroacrylamide; 552 205 N-(4-(4-amino-7-cyano-3-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl-1H- Pyrro[3,2-c]pyridin-2-yl)-3-methylphenyl)-2-fluoroacrylamide; 570 206 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; 534 207 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; 533 208 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; 542 209 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; 572 210 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; 590 211 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; 554 212 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; 553 213 N-(4-(4-amino-7-cyano-1-methyl-3-(4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)-1H- Pyrro[3,2-c]pyridin-2-yl)-3-fluorophenyl)-2-fluoroacrylamide; 526 214 N-(4-(4-amino-7-cyano-3-(4-((5-fluoro-4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H- Pyrro[3,2-c]pyridin-2-yl)-3-fluorophenyl)-2-fluoroacrylamide; 556 215 N-(4-(4-amino-7-cyano-3-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl-1H- Pyrro[3,2-c]pyridin-2-yl)-3-fluorophenyl)-2-fluoroacrylamide; 574 216 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; 538 217 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; 537 218 N-(4-(4-amino-7-cyano-1-methyl-3-(4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)-1H- Pyrro[3,2-c]pyridin-2-yl)-3-methylphenyl)acrylamide; 504 219 N-(4-(4-amino-7-cyano-3-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl-1H- Pyrro[3,2-c]pyridin-2-yl)-3-methylphenyl)acrylamide; 552 220 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; 516 221 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; 515 222 N-(4-(4-amino-7-cyano-1-methyl-3-(4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)-1H- Pyrro[3,2-c]pyridin-2-yl)-3-chlorophenyl)acrylamide; 524 223 N-(4-(4-amino-7-cyano-3-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl-1H- Pyrro[3,2-c]pyridin-2-yl)-3-chlorophenyl)acrylamide; 572 224 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; 536 225 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; 535 226 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; 508 227 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; 519 228 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-enthiamide; 550 229 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; 536 230 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; 564 231 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; 582 232 N-(4-(4-amino-7-cyano-3-(4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-(2,2,2-trifluoro Ethyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; 618 233 N-(4-(4-amino-7-cyano-3-(4-((4-(difluoromethyl)-5-fluoropyrimidin-2-yl)oxy)phenyl)-1-methyl Base-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; 556 234 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; 574 235 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; 572 236 N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl) Oxy)phenyl)-1-methyl-1H-pyrrole[3,2-c]pyridin-2-yl)phenyl)acrylamide; 576 237 N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl-1H- Pyrro[3,2-c]pyridin-2-yl)-3,5-difluorophenyl)methacrylamide; 570 238 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; 566 239 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; 584 240 N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H- Pyrro[3,2-c]pyridin-2-yl)phenyl)acrylamide; 536 241 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; 572 242 N-(4-(4-amino-3-(4-((5-chloro-4-(trifluoromethyl)pyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl Base-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; 590 243 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; 608 244 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; 584 245 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; 604 246 N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H- Pyrro[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide; 564 247 N-(4-(4-amino-7-cyano-1-methyl-3-(4-((4-(trifluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1H- Pyrro[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide; 584 248 N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((4-(trifluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl Base-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)methacrylamide; 602 249 N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl Base-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)butan-2-amide; 566 250 N-(4-(4-amino-3-(4-((5-chloro-4-(difluoromethyl)pyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl Base-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; 572 251 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; 590 252 N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl Base-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)-2-fluoroacrylamide; 572 253 N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H- Pyrro[3,2-c]pyridin-2-yl)phenyl]-2-fluoroacrylamide; 554 254 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; 535 255 N-(4-(4-amino-3-(4-((5-chloro-6-methylpyridin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl Base-1H-pyrrolo[3,2-c]pyridin-2-yl]phenyl)acrylamide; 553 256 N-(4-(4-amino-3-(3-chloro-4-((5-chloro-4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl Base-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; 570 257 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; 550 258 N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl Base-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)methacrylamide; 602 259 N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl Base-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)acrylamide; 568 260 N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H- Pyrro[3,2-c]pyridin-2-yl)-3-methylphenyl)acrylamide; 550 261 N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl Base-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-methylphenyl)-2-fluoroacrylamide; 586 262 N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H- Pyrro[3,2-c]pyridin-2-yl)-3-methylphenyl)-2-fluoroacrylamide; 568 263 N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl Base-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)acrylamide; 588 264 N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H- Pyrro[3,2-c]pyridin-2-yl)-3-chlorophenyl)acrylamide; 570 265 N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl Base-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-chlorophenyl)-2-fluoroacrylamide; 606 266 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; 588 267 N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl Base-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorobenzene)acrylamide; 572 268 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; 554 269 N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl or 590 270 N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H- Pyrro[3,2-c]pyridin-2-yl)-3-fluorophenyl)-2-fluoroacrylamide. 572

Biochemical and cellular activity

Example A: Enzymology experiment

The compounds of the present invention were tested for their effect on the enzymatic activities of FGFR1, FGFR2 and FGFR3.

According to the operation manual, the enzymatic activity of the compound of the present invention was tested using KinEASE-TK kit (CisBio, Cat. No. 62TKOPEC). The proteins required for the experiment were purchased from Carna Company (FGFR1, cat.08-133; FGFR2, cat.no.08-134; FGFR3 cat.no.08-135). The final concentrations used during the experiments were 0.2nM, 0.07nM and 0.2nM for FGFR1, FGFR2 and FGFR3, respectively. The concentration of the compound stock solution is 10mM. When used, it is diluted 3 times to 10 concentration points. The compound and protein were incubated at room temperature for 10 minutes, and then the substrate and ATP mixture were added and reacted at room temperature for 45 minutes. Then, add the mixture of TK-antibody-Cryptate and Sa-XL665 and incubate at room temperature for 60 minutes. Finally, a microplate reader (Molecular Devices, i3x) was used at the excitation wavelength of 320 nm to read the signal values at the emission wavelengths of 615nm and 665nm respectively. Use Prism 7 to analyze raw data and calculate IC50 values.

The IC50 value of FGFR2 enzymatic experiment and the selectivity results for FGFR1 and FGFR3 are shown in Table 4.

Compounds with IC50 values on FGFR2 that are less than or equal to 5nM are marked with "A+", greater than 5nM but less than or equal to 10nM are marked with "A", and greater than 10nM are marked with "B".

Compounds with selectivity on FGFR1 greater than or equal to 500 are marked with "A+", compounds with selectivity less than 500 but greater than or equal to 300 are marked with "A", compounds with selectivity less than 300 but greater than or equal to 200 are marked with "B", and compounds with selectivity less than 200 but greater than or equal to 100 are marked with "B". Marked with "C".

Compounds with selectivity on FGFR3 greater than or equal to 150 are marked with "A+", compounds with selectivity less than 150 but greater than or equal to 100 are marked with "A", and compounds with selectivity less than 100 but greater than or equal to 25 are marked with "B".

Example B: Cell proliferation assay

The effects of compounds of the invention on SNU16 cell proliferation were tested.

SNU16 cells were seeded in a 96-well bottom transparent white plate (Costar, Cat. No. 3610) at a density of 5,000 cells per well, and the culture medium volume per well was 100 μl. The concentration of the compound stock solution is 10mM, and when used, it is diluted 3-fold to 9 concentration points. Add 0.5μl to each well, and add 0.5ul DMSO to the control well. Cells were incubated in a 37°C, 5% CO2 incubator for 72 hours. During detection, add 50 μl CellTiter-Glo reagent (Promega, G7572) to each well and shake for 10 minutes at room temperature. Chemiluminescence was read using a microplate reader (Molecular Devices, i3x), and IC50 values were calculated using Prism 7.

The results of SNU16 cell proliferation experiments are shown in Table 4.

Compounds with IC50 less than or equal to 10nM are marked with "A+", compounds with IC50 greater than 10nM but less than or equal to 50nM are marked with "A", and compounds with IC50 greater than 50nM are marked with "B".

Table 4: Compound serial number FGFR2 IC50 Selectivity SNU-16 IC50 FGFR1/FGFR2 FGFR3/ FGFR2 0* B C B A+ 1 A+ A B A+ 2 A+ A+ A+ A+ 4 A+ A+ A A+ 5 A+ A A+ A+ 8 A A+ A+ A+ 9 B A+ A+ A+ 11 B A+ A+ A+ 16 A+ A+ A B 17 A+ A B A+ 18 A+ A+ A A+ 20 A+ A A A+ twenty two A+ A A+ A+ 26 A+ A B A+ 27 A A+ A+ A+ 28 A A+ A+ A+ 29 A+ A+ A A+ 31 A+ A+ A A+ 32 A+ A+ A A+ 33 A+ A+ B A+ 37 A+ A+ B A+ 38 A A+ A+ A+ 40 A+ B B A+ 44 A+ A B A+ 45 A+ A+ A+ A+ 46 A+ A+ B A+ 47 A+ A+ B A+ 48 A+ C B A+ 51 A+ B B A+ 52 A+ B B A+ 63 A+ A+ A+ A+ 64 A+ A+ A A+ 65 A B A+ A+ 69 A+ C A+ A+ 72 A+ B A+ A+ 99 A+ C A A+ 100 A+ A A+ A+ 101 A+ C A / 102 A C A+ A+ 108 A+ B A+ A+ 110 A+ A+ B A+ 113 B A+ B / 129 B A+ A+ A+ 130 B A+ A+ A+ 135 A+ A+ A+ A+ 157 A+ A+ A+ A+ 0* The compound with ID 0 is published in the PCT application with international publication number WO 2020/231990A1, and its chemical name is: N-(4-amino-5-(3-fluoro-4-((4-methylpyrimidine) -2-yl)oxy)phenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)phenyl)methacrylamide

Example C: Rat pharmacokinetic experiment

The research protocols used in animal experiments have been reviewed and approved by the IACUC Committee of Yingweiwo Biotechnology Co., Ltd.

Experimental animal information: Sprague-Dawley (SD) rats, SPF grade, 6-8 weeks old, male, weighing 200-250g, purchased from Viton Lever.

Preparation preparation: Use the solvent formula 5% DMSO + 10% Solutol + 85% HPβCD (20% HPβCD) to prepare solutions for oral and intravenous injection with final concentrations of 1.5 mg/ml and 0.6 mg/ml, respectively.

Route of administration: oral administration and intravenous injection;

Dosage: oral gavage dose 15mg/kg, intravenous injection dose 3mg/kg;

Plasma was collected at 0.083, 0.25, 0.5, 1, 2, 4, 6, 8 and 24 hours after administration, and pharmacokinetic parameters (T _1/2 , C _{max ,} AUC _{0- ∞} , Cl).

The results of pharmacokinetic experiments are shown in Table 5.

table 5: Compound serial number Cl (mL/min/kg) T _1/2 (hour) C _max (ng/mL) AUC _{0- ∞} (hour*ng/mL) 0* 49 1.5 244 614 1 19 0.98 509 1238 2 3.1 6 621 2703 63 5.4 1.3 442 2068 91 3.4 2.7 615 1511 0* The compound with ID 0 is published in the PCT application with international publication number WO 2020/231990A1, and its chemical name is: N-(4-amino-5-(3-fluoro-4-((4-methylpyrimidine) -2-yl)oxy)phenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)phenyl)methacrylamide.

Instructions incorporated by reference

All publications and patents mentioned in this filing are hereby incorporated by reference in their entirety for all purposes as if each individual publication or patent was specifically and individually incorporated by reference. In the event of a conflict, this application document, including any definitions contained in this application document, will control.

equivalent substitution

Although specific embodiments have been discussed and disclosed, the foregoing description is illustrative and not restrictive. Many variations of the present disclosure may become apparent to those skilled in the art upon review of this specification. The full scope of the disclosure should be determined by reference to the full scope of all claims and their equivalents, together with the specification and possible variations.

Unless otherwise stated, all numbers expressing amounts of ingredients, reaction conditions, etc. used in the specification and claims are to be understood to be modified in all cases by the term "about." Therefore, unless stated to the contrary, the numerical parameters set forth in this specification and its appended claims are approximations that may vary depending on the properties intended to be obtained by the invention.

Claims (45)

Compounds represented by formula (I): Formula (1) or its pharmaceutically acceptable salts, prodrugs, solvates, hydrates, tautomers and isomers, wherein: R ₁ is selected from H, CN or CONH ₂ ; R ₂₁ is selected from H, D, CN, C _1-3 alkyl, C _1-3 alkoxy, C _3-6 cycloalkyl, -(CH ₂ ) _0-2 -NHC _1-3 alkyl, -(CH ₂ ) _{0- 2} N(C _1-3 alkyl) ₂ or 3- to 6-membered saturated heterocycle with 1 or 2 heteroatoms selected from N, O or S; and each independently optionally unsubstituted or each independently Optionally substituted by 1, 2 or 3 groups selected from D, OH, halogen, C _1-3 alkyl, C _1-3 alkoxy or C _3-6 cycloalkyl; Ring B is phenylene , a divalent 5- or 6-membered saturated or partially unsaturated heterocyclic ring having 1 or 2 independently selected from N, O or S heteroatoms, or a 5- or 6-membered saturated or partially unsaturated heterocycle having 1 or 2 A heteroarylene ring independently selected from N, O or S heteroatoms; Ring D is a phenylene group, and the divalent 5- or 6-membered one or two are independently selected from N, O or S heteroatoms. Atomically saturated or partially unsaturated heterocycles, divalent 9- or 10-membered saturated or partially unsaturated fused heterocycles with 1 or 2 independently selected N, O or S heteroatoms , a 5- or 6-membered heteroaromatic ring with 1 or 2 independently selected from N, O or S heteroatoms, or a 9- or 10-membered heteroaromatic ring with 1 or 2 independently selected from N, O or a fused heteroaromatic ring of S heteroatoms; each R ₂₂ is independently optionally selected from H, D, halogen, CN, NH ₂ , OH, C _1-3 alkyl, C _1-3 alkoxy , C _3-6 cycloalkyl, -(CH ₂ ) _0-2 -NHC _1-3 alkyl or -(CH ₂ ) _0-2 N(C _1-3 alkyl) ₂ , and each independently and optionally Unsubstituted or each independently optionally substituted by 1, 2 or 3 R _z ; Each R ₂₅ is independently optionally H, D, halogen, CN, OH, R ^′′ , N(R′′) ₂ , OR′′ or _-SR ′′; each O) ₂ -, -CO-, -NH-, -CH ₂ -, -CONH-, -NHCO-, -CONHCH ₂ -, -NHCONH-, -NHCOCH ₂ - or -NHCOCH ₂ CH ₂ -, and each _CH2 is independently optionally unsubstituted or independently optionally substituted with 1, 2 or 3 groups selected from D, halogen, C _1-3 alkyl or C _1-3 haloalkyl, and each NH is independently optionally substituted Optionally unsubstituted or independently optionally substituted by 1, 2 or 3 C _1-3 alkyl groups; Is a divalent bond or a trivalent bond; 1) When When it is a trivalent bond, each R ₂₃ does not exist, and each R ₂₄ is independently selected from H, D, -C _0-3 alkylene -N(R′′) ₂ , -C _0-3 Alkylene-OR'' or R''; and each independently optionally unsubstituted or each independently optionally substituted by 1, 2 or 3 groups selected from D or halogen; 2) when When it is a divalent bond, each R ₂₃ or each R ₂₄ is independently selected from H, D, halogen, -C _0-3 alkylene -N(R′′) ₂ , -C _0-3 sub Alkyl-OR'' or R''; and each independently optionally unsubstituted or each independently optionally substituted with 1, 2 or 3 groups selected from D or halogen; each W independently optionally optionally substituted From C _1-3 alkyl, phenyl, 4- to 6-membered saturated or partially saturated heterocyclyl with 1 or 2 independently selected from N, O or S heteroatoms, 5- or 6- There are 1 to 3 membered heteroaryl groups independently selected from N, O or S heteroatoms, or 3- to 6-membered saturated or partially saturated carbocyclic rings, and each independently is optionally unsubstituted or substituted. 1, 2 or 3 R _w substituted; each R _w is independently selected from D, halogen, OH, CN, NH ₂ , C _1-3 alkyl, C _1-3 haloalkyl, C _3-6 ring Alkyl, C _2-3 alkenyl or C _2-3 alkynyl; and each is independently optionally unsubstituted or each is independently optionally substituted with 1, 2 or 3 Rz; each y is independently optionally selected from 0, 1, 2, 3 or 4; each R _z is independently arbitrarily selected from H, D, halogen, CN, -N(R′′) ₂ , -OR′′ or R′′; each R′ ' is independently optionally C _1-3 ^{‏ alkyl} or C _3-6 cycloalkyl, and each independently optionally is unsubstituted or each independently optionally substituted by 1, 2 or 3 groups selected from halogen or D group replaced. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein: Ring B is a phenylene group, a divalent 5- or 6-membered saturation group with 1 or 2 independently selected from N heteroatoms. or partially unsaturated heterocyclic group, or a 5- or 6-membered heteroarylene group having 1 or 2 independently selected N heteroatoms. The compound according to claim 1 or 2 or a pharmaceutically acceptable salt thereof, wherein: ring B is , , , or . The compound according to any one of claims 1-3 or a pharmaceutically acceptable salt thereof, wherein: Ring D is a phenylene group, and 1 or 2 of the divalent 9- or 10-membered ones are independently selected from A saturated or partially unsaturated fused heterocyclyl group of N, O or S heteroatoms, or a 9- or 10-membered fused subunit having 1 or 2 independently selected from N, O or S heteroatoms. Heteroaromatic ring group. The compound according to any one of claims 1-4 or a pharmaceutically acceptable salt thereof, wherein: Ring D is , or . The compound according to any one of claims 1-4 or a pharmaceutically acceptable salt thereof, wherein: R ₁ is CN. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein: the compound is a compound represented by formula (II): Formula (II). The compound according to any one of claims 1-7 or a pharmaceutically acceptable salt thereof, wherein: the R ₂₁ is selected from H, D, CN, NH ₂ , OH, methyl, ethyl, propyl , isopropyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, -(CH ₂ ) _0-2 -NHCH ₃ , -(CH ₂ ) _0-2 -NHCH ₂ CH ₃ , -(CH ₂ ) _0-2 N(CH ₃ ) ₂ , -(CH ₂ ) _0-2 N(CH ₂ CH ₃ ) ₂ , -(CH ₂ ) _0-2 N(CH ₃ )( CH ₂ CH ₃ ), a 4-membered saturated heterocycle, a 5-membered saturated heterocycle, or a 6-membered saturated heterocycle with 1 or 2 heteroatoms selected from N or O heteroatoms; and each independently Arbitrarily unsubstituted or each independently optionally substituted by 1, 2 or 3 selected from D, OH, F, Cl, Br, methoxy, ethoxy or propoxy; the R ₂₂ is independently optional Selected from H, D, F, Cl, Br, CN, NH ₂ , OH, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, cyclopentyl group, cyclohexyl, -(CH ₂ ) _0-2 -NHCH ₃ , -(CH ₂ ) _0-2 -NHCH ₂ CH ₃ , -(CH ₂ ) _0-2 N(CH ₃ ) ₂ , -(CH ₂ ) _0-2 N(CH ₂ CH ₃ ) ₂ or -(CH ₂ ) _0-2 N(CH ₃ CH ₂ CH ₃ ), each independently optionally unsubstituted or each independently optionally substituted by 1, 2 or 3 R _z replaced. The compound according to any one of claims 1-8 or a pharmaceutically acceptable salt thereof, wherein: the R ₂₁ is selected from H, D, CN, NH ₂ , OH, methyl, ethyl, methoxy group, cyclopropyl, cyclohexyl, 4-membered saturated heterocyclic ring or 5-membered saturated heterocyclic ring with 1 or 2 selected from N or O heteroatoms; and each independently is optionally unsubstituted or each independently Optionally substituted by 1, 2 or 3 groups selected from D, OH, F or Cl; each R ₂₂ is selected from H, D, F, Cl, CN, NH ₂ , OH, methyl, ethyl, Methoxy, ethoxy, cyclopropyl, cyclobutyl, -NHCH ₃ , -CH ₂ NHCH ₃ , -CH ₂ CH ₂ NHCH ₃ , -CH ₂ NHCH ₂ CH ₃ , -N(CH ₃ ) ₂ , -CH ₂ N(CH ₃ ) ₂ , -(CH ₂ ) ₂ N(CH ₃ ) ₂ , -N(CH ₃ CH ₂ CH ₃ ), -CH ₂ N(CH ₃ CH ₂ CH ₃ ) or -(CH ₂ ) ₂ N(CH ₃ CH ₂ CH ₃ ); and each independently optionally unsubstituted or each independently optionally substituted with 1, 2 or 3 R _z . The compound according to any one of claims 1-9 or a pharmaceutically acceptable salt thereof, wherein: the R ₂₁ is selected from , , , , , , , , , , , , , ,or ; The R ₂₂ is selected from , , , , , , , , , , , , , , or . The compound according to any one of claims 1-10 or a pharmaceutically acceptable salt thereof, wherein: the R ₂₁ is selected from , , , , , , , or ; The R ₂₂ is selected from , , , , , , , , or . The compound according to any one of claims 1-11 or a pharmaceutically acceptable salt thereof, wherein: each R ₂₅ is independently H, D, F, Cl, Br, CN, NH ₂ , OH, Methyl, ethyl, propyl, isopropyl, -S-methyl, -S-ethyl, -S-propyl, methoxy, ethoxy or propoxy; and each independently optionally Substituted or each independently optionally substituted by 1, 2 or 3 groups selected from D, F, Cl or Br. The compound according to any one of claims 1-12 or a pharmaceutically acceptable salt thereof, wherein: each R ₂₅ is independently H, D, F, Cl, methyl, ethyl, -S- Methyl, -S-ethyl, methoxy or ethoxy; and each independently optionally unsubstituted or each independently optionally substituted with 1, 2 or 3 groups selected from D or F. The compound according to any one of claims 1-13 or a pharmaceutically acceptable salt thereof, wherein: each R ₂₅ is independently H, D, F, Cl, methyl, ethyl, -S- Methyl, methoxy or ethoxy; and each independently optionally unsubstituted or each independently optionally substituted with 1, 2 or 3 F. The compound according to any one of claims 1-14 or a pharmaceutically acceptable salt thereof, wherein: each X or each L is independently selected from covalent bonds, -O-, -CO -, -NH-, -CH ₂ -, -CONH- or -NHCO-. The compound according to any one of claims 1-15 or a pharmaceutically acceptable salt thereof, wherein: each X is independently and arbitrarily selected from -NH-; each L is independently and arbitrarily selected from -O-, -NH-, -CONH- or -NHCO-. The compound according to any one of claims 1-16 or a pharmaceutically acceptable salt thereof, wherein: is a divalent bond, and each R ₂₃ or each R ₂₄ is independently selected from H, D, F, Cl, Br, -N(R′′) ₂ , -CH ₂ N(R′′ ) ₂ , -(CH ₂ ) ₂ N(R′′) _{2 ,} -(CH ₂ ) ₃ N(R′′) ₂ or R′′; and each independently is optionally unsubstituted or each independently optionally is 1, 2 or 3 groups selected from D, F, Cl or Br are substituted. The compound according to any one of claims 1-17 or a pharmaceutically acceptable salt thereof, wherein: the is a divalent bond, and each R ₂₃ or each R ₂₄ is independently selected from H, D, F, Cl, methyl, ethyl, propyl, isopropyl or cyclopropyl; and each is independently selected Optionally unsubstituted or each independently optionally substituted by 1, 2 or 3 groups selected from D, F or Cl. The compound according to any one of claims 1-18 or a pharmaceutically acceptable salt thereof, wherein: is a divalent bond, and each R ₂₃ or each R ₂₄ is independently optionally selected from H, D, F or methyl; and the methyl group is independently optionally unsubstituted or independently optionally substituted 1, 2 or 3 groups selected from D or F are substituted. The compound according to any one of claims 1-16 or a pharmaceutically acceptable salt thereof, wherein: It is a trivalent bond, each R ₂₃ does not exist, and each R ₂₄ is independently selected from H, D, methyl, ethyl, propyl, isopropyl or cyclopropyl; And each independently is optionally unsubstituted or each independently is optionally substituted with 1, 2 or 3 groups selected from D, F or Cl. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1-16 or 20, wherein: said is a trivalent bond, each R ₂₃ does not exist, and each R ₂₄ is independently selected from H, D or methyl; and the methyl is independently unsubstituted or independently is optionally substituted by 1, 2 or 3 groups selected from D or F. The compound according to any one of claims 1-21 or a pharmaceutically acceptable salt thereof, wherein: said W is independently selected from methyl, phenyl, 4-, 5- or 6-membered 1 or 2 saturated heterocycles selected from N, O or S heteroatoms, 5- or 6-membered heteroaryls with 1 or 2 heteroatoms selected from N or S, or 3-, 4-, 5- Or a 6-membered saturated carbocyclic ring. The compound according to any one of claims 1-22 or a pharmaceutically acceptable salt thereof, wherein: said W is independently and arbitrarily selected from a 5- or 6-membered saturated heterocycle with 1 N atom, 5-membered heteroaromatics with 1 N atom and 1 S atom, 6-membered heteroaromatics with 1 or 2 N atoms, 3-membered saturated carbocyclic rings, 4-membered saturated carbocyclic rings , 5-membered saturated carbocyclic ring or 6-membered saturated carbocyclic ring. The compound according to any one of claims 1-23 or a pharmaceutically acceptable salt thereof, wherein: each R _w is independently selected from D, F, Cl, Br, OH, methoxy , CN, NH ₂ , methyl, ethyl, propyl, isopropyl, F or Cl substituted methyl, F or Cl substituted ethyl, F or Cl substituted propyl, F or Cl substituted isopropyl group, cyclopropyl, cyclobutyl, cyclopentyl, vinyl or ethynyl; and each is independently optionally unsubstituted or each is independently optionally substituted by 1, 2 or 3 _Rz . The compound according to any one of claims 1-24 or a pharmaceutically acceptable salt thereof, wherein: each Rw is independently selected from D, F, Cl, methyl, 1, 2 or 3 Each is selected from methyl, methoxy or cyclopropyl substituted by F or D groups. The compound according to any one of claims 1-25 or a pharmaceutically acceptable salt thereof, wherein: each R _z is independently selected from D, F, Cl, Br, CN, -N ( R′′) ₂ , -OR′ or R′′. The compound according to any one of claims 1-26 or a pharmaceutically acceptable salt thereof, wherein: each R _z is independently selected from D, F, Cl, Br, CN, -NH ₂ , methyl, ethyl, propyl or isopropyl. The compound according to any one of claims 1-27 or a pharmaceutically acceptable salt thereof, wherein: each Rz is independently selected from D, F, Cl or methyl. The compound according to any one of claims 1-28 or a pharmaceutically acceptable salt thereof, wherein: each R′′ is independently methyl, ethyl, propyl, isopropyl, cyclopropyl , cyclobutyl or cyclopentyl; and each is independently optionally unsubstituted or each is independently optionally substituted by 1, 2 or 3 groups selected from F, Cl or D. The compound according to any one of claims 1-29 or a pharmaceutically acceptable salt thereof, wherein: each R′′ is independently selected from methyl, ethyl or propyl; and each R′′ is independently selected from methyl, ethyl or propyl; Unsubstituted or each independently optionally substituted by 1, 2 or 3 groups selected from D or F. Compounds independently selected from: 4-(2-(4-Acrylamidephenyl)-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-(4-(2-fluoroacrylamide)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridine-3- base)-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- Pyrro[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- Pyrro[3,2-c]pyridin-2-yl)phenyl]-2-fluoroacrylamide; 4-(2-(4-Acrylamidephenyl)-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 Base-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- Pyrro[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 Base-1H-pyrrolo[3,2-c]pyridin-2-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-7-cyano-3-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl- 1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; 2-(4-Acrylamidephenyl)-4-amino-3-(3-methoxy-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-1-methyl Base-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-Acrylamidephenyl)-4-amino-7-cyano-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-cyclopropyl-2 -Methoxybenzamide; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-(2-hydroxyethyl)-1H-pyrrolo[3,2-c]pyridine-3- base)-N-cyclobutyl-2-methoxybenzamide; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-(2-methoxyethyl)-1H-pyrrolo[3,2-c]pyridine- 3-yl)-N-cyclobutyl-2-methoxybenzamide; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N- Isobutyl-2-methoxybenzamide; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N- cyclobutylbenzamide; 4-(2-(4-Acrylamidephenyl)-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]pyridine -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-7-cyano-2-(4-(2-fluoroacrylamide)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridine-3- base)-N-cyclobutylbenzamide; 4-(4-Amino-7-cyano-2-(4-(2-fluoroacrylamide)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridine-3- base)-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-Acrylamide-2-methoxyphenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridine-3 -yl)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(2-(4-Acrylamide-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-(2-(4-Acrylamide-2-methoxyphenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridine-3 -base)-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]pyridine-3- base)-N-isopropyl-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]pyridine-2- Base) benzene) acrylamide; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N- (2,2-difluorocyclopropyl)-2-methoxybenzamide; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N- (3-fluorocyclobutyl)-2-methoxybenzamide; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-2- Methoxy-N-(1-methylcyclopropyl)benzamide; 4-(2-(4-Acrylamidephenyl)-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; 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; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N- (3,3-difluorocyclobutyl)-2-methoxybenzamide; 4-(2-(4-Acrylamidephenyl)-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- Pyrro[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-propenylpyridin-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-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N- (2,2-difluoroethyl)-2-methoxybenzamide; 4-(2-(1-Acrylylpyrrolidin-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-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N- ((1-fluorocyclopropyl)methyl)-2-methoxybenzamide; 4-(2-(4-Acrylamide-3-fluorophenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) -N-cyclopropyl-2-methoxybenzamide; 4-(2-(4-Acrylamide-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-propenyl-2,5-dihydro-1H-pyrrol-3-yl)-4-amino-7-cyano-1-methyl-1H-pyrrole [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- Cyclopropyl-2-methoxybenzamide; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-(2-fluoroethyl)-1H-pyrrolo[3,2-c]pyridine-3- base)-N-cyclopropyl-2-methoxybenzamide; N-(4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) -2-methoxyphenyl)cyclopropanemethamide; 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; 4-(2-(4-Acrylamidephenyl)-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- Pyrro[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; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1H-pyrrolo[3,2-c]pyridin-3-yl)-2-methoxy-N -(2,2,2-trifluoroethyl)benzamide; N-(4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) -2-methoxyphenyl)cyclobutamide; N-(4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) -2-methoxyphenyl)cyclopentamide; 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-(2-(4-Acrylamide-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-propylamidophenyl)-1-methyl-1H-pyrrolo[3,2-c] Pyridin-2-yl)phenyl)acrylamide; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-(2-fluoroethyl)-1H-pyrrolo[3,2-c]pyridine-3- base)-N-(3,3-difluorocyclobutyl)-2-methoxybenzamide; 4-(2-(4-Acrylamide-2-fluorophenyl)-4-amino-7-cyano-1H-pyrrolo[3,2-c]pyridin-3-yl)-N-(3 ,3-difluorocyclobutyl)-2-methoxybenzamide; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-isopropyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N -(3,3-difluorocyclobutyl)-2-methoxybenzamide; N-(4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) -2-methoxyphenyl)-N-methylcyclopropanemethamide; N-(4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) Phenyl)cyclopropanemethamide; N-(4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) -2-methoxyphenyl)-3,3-difluorocyclobutane-1-methamide; N-(4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) -2-methoxyphenyl)-1-methylcyclopropane-1-methamide; N-(4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) -2-methoxyphenyl)-1-fluorocyclopropane-1-methamide; N-(4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) -2-methoxyphenyl)-1-(trifluoromethyl)cyclopropane-1-methamide; 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-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) -2-methoxyphenyl)-2,2-difluorocyclopropane-1-methamide; N-(4-(4-amino-7-cyano-3-(4-(3-cyclopropylureido)-3-methoxyphenyl)-1-methyl-1H-pyrrolo[3 ,2-c]pyridin-2-yl)phenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(4-(cyclobutylamino)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2- Base)phenyl)acrylamide; N-(4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridin-3-yl) -2-methoxyphenyl)azetidine-1-methamide; 4-(2-(4-Acrylamide-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-Acrylamidephenyl)-4-amino-7-cyano-1-(2-methoxyethyl)-1H-pyrrolo[3,2-c]pyridine- 3-yl)-N-(3,3-difluorocyclobutyl)-2-methoxybenzamide; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-(2-fluoroethyl)-1H-pyrrolo[3,2-c]pyridine-3- base)-2-methoxy-N-(2,2,2-trifluoroethyl)benzamide; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-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-(pyrrolidin-1-yl)phenyl)-1H-pyrrolo[3,2-c]pyridine- 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-Acrylamidephenyl)-4-amino-7-cyano-1-(2-methoxyethyl)-1H-pyrrolo[3,2-c]pyridine- 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-7-cyano-1-methyl-3-(1-methyl-1H-indol-5-yl)-1H-pyrrolo[3,2-c]pyridine -2-yl)phenyl)acrylamide; N-(4-(4-amino-3-(benzo[b]thiophen-2-yl)-7-cyano-1-methyl-1H-pyrrolo[3,2-c]pyridine-2- Base)phenyl)acrylamide; 4-(2-(4-Acrylamidephenyl)-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-Acrylamidephenyl)-4-amino-7-cyano-1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-c ]pyridin-3-yl)-2-methoxy-N-(2,2-difluoroethyl)benzamide; 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-(2-(4-Acrylamidephenyl)-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-Acrylamidephenyl)-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-7-cyano-3-(3-methoxy-4-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl) (yl)phenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)acrylamide; 4-(2-(4-Acrylamidephenyl)-4-amino-7-cyano-1-cyclopropyl-1H-pyrrolo[3,2-c]pyridin-3-yl)-N -Cyclopropyl-2-methoxybenzamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((6-methylpyridin-2-yl)oxy)phenyl)-1-methyl-1H- Pyrro[3,2-c]pyridin-2-yl]phenyl)acrylamide; N-(4-(4-amino-7-cyano-3-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)-3-fluorophenyl)-1-methyl Base-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 Base-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-7-cyano-3-(3-fluoro-4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)-1-methyl Base-1H-pyrrolo[3,2-c]pyridin-2-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- Pyrro[3,2-c]pyridin-2-yl)phenyl]acrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-((1-methyl-1H-pyrazol-3-yl)oxy)phenyl)-1H- Pyrro[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-7-cyano-3-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)-3-fluorophenyl)-1-methyl Base-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 Base-1H-pyrrole[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-pyrrole[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]pyridine -2-yl)-3-fluorophenyl)methacrylamide; 4-(4-amino-7-cyano-2-(2-fluoro-4-methacrylamidephenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridine-3- methyl)-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-pyrrole And[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-pyrrole And[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]pyridine-2- methyl)-3-fluorophenyl)methacrylamide; 4-(4-Amino-7-cyano-2-(2-fluoro-4-methacrylamidephenyl)-1-methyl-1H-pyrrolo[3,2-c]pyridine-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]pyridine -2-yl)-3-fluorophenyl)methacrylamide; N-(4-(4-amino-7-cyano-1-methyl-3-(4-(pyridin-2-yloxy)phenyl)-1H-pyrrolo[3,2-c]pyridine -2-yl)phenyl]acrylamide; N-(4-(4-amino-7-cyano-3-(3-fluoro-4-((5-fluoropyrimidin-2-yl)oxy)phenyl)-1-methyl-1H-pyrrole And[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 Base-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-pyrrole And[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- Pyrro[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-pyrrole And[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- Pyrro[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- Pyrro[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]pyridine-2- Base) benzene) acrylamide; N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)-3-fluorophenyl)-7-cyano-1-methyl Base-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]pyridine -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- Pyrro[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 Base-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 Base-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 Base-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- Pyrro[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 base)phenyl)-1-methyl-1H-pyrrole[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-(tetrafluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1H-pyrrolo[3 ,2-c]pyridin-2-yl)phenylacrylamide; 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-pyrrole And[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- Pyrrole[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- Pyrro[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; N-(4-(4-amino-3-(3-chloro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H- Pyrro[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]pyridine-2- (base)-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-methylphenyl)methacrylamide; N-(4-(4-amino-7-cyano-3-(4-((4-(difluoromethyl)pyrimidin-2-yl)oxy)phenyl)-1-methyl-1H- Pyrro[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- Pyrrole[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- Pyrro[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 Base-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 Base-1H-pyrrole[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 Base-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- Pyrro[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- Pyrro[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- Pyrro[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- Pyrro[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- Pyrro[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- Pyrro[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- Pyrro[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- Pyrro[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- Pyrro[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- Pyrro[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-enthiamide; 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-trifluoro Ethyl)-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 Base-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-pyrrole[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- Pyrro[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- Pyrro[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 Base-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- Pyrro[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- Pyrro[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 Base-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 Base-1H-pyrrolo[3,2-c]pyridin-2-yl)phenyl)butan-2-amide; N-(4-(4-amino-3-(4-((5-chloro-4-(difluoromethyl)pyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl Base-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 Base-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- Pyrro[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 Base-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 Base-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 Base-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 Base-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- Pyrro[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 Base-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- Pyrro[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 Base-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- Pyrro[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 Base-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 Base-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-fluorobenzene)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 or N-(4-(4-amino-3-(4-((5-chloro-4-methylpyrimidin-2-yl)oxy)phenyl)-7-cyano-1-methyl-1H- Pyrro[3,2-c]pyridin-2-yl)-3-fluorophenyl)-2-fluoroacrylamide. A pharmaceutical composition comprising the compound described in claim 1-31 and a pharmaceutically acceptable carrier. A pharmaceutical composition comprising the compound described in claim 32 and a pharmaceutically acceptable carrier. A method for inhibiting FGFR2 signaling activity in a subject, comprising administering to a subject in need a therapeutically effective amount of the compound described in any one of claims 1-31, or the drug combination described in any one of claims 32-33 things. A method for inhibiting FGFR2 signaling activity in a subject, comprising administering to a subject in need a therapeutically effective amount of the compound described in claim 31, or the pharmaceutical composition described in any one of claims 32-33. A method of treating a subject's disease, comprising administering to a subject in need of treatment a therapeutically effective amount of the compound described in any one of claims 1-31, or the pharmaceutical composition described in any one of claims 32-33 , wherein: the disease is cholangiocarcinoma, liver cancer, breast cancer, prostate cancer, lung cancer, thyroid cancer, gastric cancer, ovarian cancer, rectal cancer, endometrial cancer or urothelial cancer. A method of treating a subject's disease, comprising administering to a subject in need of treatment a therapeutically effective amount of the compound described in claim 31, or the pharmaceutical composition described in any one of claims 32-33, wherein: said The disease is cholangiocarcinoma, liver cancer, breast cancer, prostate cancer, lung cancer, thyroid cancer, gastric cancer, ovarian cancer, rectal cancer, endometrial cancer or urothelial cancer. A method for treating FGFR2-modulated diseases in a subject, comprising administering to a subject in need of treatment a therapeutically effective amount of a compound described in any one of claims 1-31, or a drug described in any one of claims 32-33 The composition, wherein: the disease is cholangiocarcinoma, liver cancer, breast cancer, prostate cancer, lung cancer, thyroid cancer, gastric cancer, ovarian cancer, rectal cancer, endometrial cancer or urothelial cancer. A method of treating FGFR2-regulated diseases in a subject, comprising administering to a subject in need of treatment a therapeutically effective amount of the compound described in claim 31, or the pharmaceutical composition described in any one of claims 32-33, wherein: The disease is cholangiocarcinoma, liver cancer, breast cancer, prostate cancer, lung cancer, thyroid cancer, gastric cancer, ovarian cancer, rectal cancer, endometrial cancer or urothelial cancer. The method according to any one of claims 36 to 39, wherein the disease is cholangiocarcinoma. The method according to claim 40, wherein the cholangiocarcinoma is intrahepatic cholangiocarcinoma. The method according to any one of claims 36 to 39, wherein the disease is liver cancer. The method according to claim 42, wherein the liver cancer is hepatocellular carcinoma. The method according to any one of claims 36 to 39, wherein: the disease is lung cancer. The method according to claim 44, wherein the lung cancer is lung squamous cell carcinoma or non-small cell lung cancer.