Biaryl bruton's tyrosine kinase inhibitors

1. A compound of formula II-b:

or a pharmaceutically acceptable salt thereof, wherein:

Q 1 , Q 2 and Q 3 are CH;

R 1 is an optionally substituted group selected from thiazolyl, thiadiazolyl and imidazolyl, wherein R 1 is optionally substituted with one or more R 10 ;

R 2 is H or C 1-6 aliphatic;

R 3 is selected from H, halogen, —C(O)N(R) 2 , —C(O)OR, —C(O)R, and C 1-6 aliphatic, wherein the C 1-6 aliphatic group is optionally substituted with hydroxyl;

R 4 is selected from H, halogen, —NO 2 , —CN, —OR, —SR, —N(R) 2 , —C(O)R, —C(O)OR, —S(O)R, —S(O) 2 R, —C(O)N(R) 2 , —SO 2 N(R) 2 , —OC(O)R, —N(R)C(O)R, —N(R)C(O)OR, —N(R)SO 2 R, —OC(O)N(R) 2 , and C 1-6 aliphatic, wherein said C 1-6 aliphatic is optionally substituted with one or more R 40 ;

or R 3 and R 4 together with their intervening atoms form fused Ring A selected from fused 5- to 7-membered monocyclic carbocycle, fused 5- to 7-membered monocyclic heterocycle having 1-2 heteroatoms selected from oxygen, nitrogen, or sulfur, wherein said fused Ring A is optionally substituted with one or more R 40 ;

each R 5 is selected from H and C 1-6 aliphatic;

R 6 is selected from H, phenyl, 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclyl, 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 1-2 heteroatoms selected from oxygen, nitrogen, or sulfur, 7- to 10-membered bicyclic heterocyclyl having 1-4 heteroatoms selected from oxygen, nitrogen, or sulfur, and 5- to 6-membered heteroaryl having 1-4 heteroatoms selected from oxygen, nitrogen, or sulfur, wherein said phenyl, 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclyl, 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 1-2 heteroatoms selected from oxygen, nitrogen, or sulfur, 7- to 10-membered bicyclic heterocyclyl having 1-4 heteroatoms selected from oxygen, nitrogen, or sulfur, and 5- to 6-membered heteroaryl having 1-4 heteroatoms selected from oxygen, nitrogen, or sulfur, are optionally substituted with one or more R 60 ; or

R 5 and R 6 , taken together with their intervening atoms, form a fused 5- to 7-membered monocyclic carbocycle or fused 5- to 7-membered monocyclic heterocycle having 1-2 heteroatoms selected from oxygen, nitrogen, or sulfur; wherein said monocyclic carbocycle or heterocycle is optionally substituted with one or more R 60 ; and

each R is independently hydrogen or C 1-6 aliphatic, phenyl, 3- to 8-membered saturated or partially unsaturated carbocyclyl ring, 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 1-2 heteroatoms selected from oxygen, nitrogen, or sulfur, or 5- to 6-membered heteroaryl having 1-4 heteroatoms selected from oxygen, nitrogen, or sulfur, wherein said C 1-6 aliphatic, phenyl, 3- to 7-membered saturated or partially unsaturated carbocyclyl ring, 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 1-2 heteroatoms selected from oxygen, nitrogen, or sulfur, or 5- to 6-membered heteroaryl having 1-4 heteroatoms selected from oxygen, nitrogen, or sulfur, are optionally substituted with one or more R 60 ; or

two R groups on the same nitrogen are taken together with their intervening atoms to form a ring selected from 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 1-2 heteroatoms selected from oxygen, nitrogen, or sulfur, or 5- to 6-membered heteroaryl having 1-4 heteroatoms selected from oxygen, nitrogen, or sulfur, wherein said ring is optionally substituted with one or more R 60 ;

each R 10 is independently selected from halogen, —OR 10a , C 1-6 aliphatic, 3- to 5-membered saturated or partially unsaturated carbocyclyl, 3- to 5-membered saturated or partially unsaturated monocyclic heterocyclyl having 1-2 heteroatoms selected from oxygen, nitrogen, or sulfur, wherein said C 1-6 aliphatic, 3- to 5-membered saturated or partially unsaturated carbocyclyl, 3- to 5-membered saturated or partially unsaturated monocyclic heterocyclyl having 1-2 heteroatoms selected from oxygen, nitrogen, or sulfur, are optionally substituted with one or more R 15 ;

each R 15 is independently selected from halogen and —OR 15a ;

R 10a is C 1-6 alkyl;

R 15a is C 1-6 alkyl;

each R 40 is independently selected from halogen, 4- to 6-membered monocyclic heterocyclyl, —N(R 40a ) 2 , —N(R 40a )C(O)(R 40b ), —N(R 40a )C(O) 2 (R 40a ), —OR 40a , —SR 40a , and —C(O) 2 R 40a ;

each R 40a is independently selected from H and C 1-6 alkyl; or two R 40a groups on the same nitrogen are taken together with their intervening atoms to form a ring selected from 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 1-2 heteroatoms selected from oxygen, nitrogen, or sulfur, or 5- to 6-membered heteroaryl having 1-4 heteroatoms selected from oxygen, nitrogen, or sulfur;

each R 40b is independently selected from C 2-6 alkenyl and 5- or 6-membered heterocyclyl having 1-2 heteroatoms selected from oxygen, nitrogen, or sulfur, wherein said 5- or 6-membered heterocyclyl having 1-2 heteroatoms selected from oxygen, nitrogen, or sulfur, is optionally substituted with one or more R 45 ;

R 45 is C 1-6 alkyl;

each R 60 is independently selected from C 1-6 alkyl, —OR 60a , —N(R 60a ) 2 , —C(O)N(R 60a ) 2 ; —C(O) 2 R 60a ; —C(O)R 60b , 3- to 6-membered saturated or partially unsaturated monocyclic carbocyclyl, 3- to 6-membered saturated or partially unsaturated monocyclic heterocyclyl having 1-2 heteroatoms selected from oxygen, nitrogen, or sulfur, and 3- to 10-membered heterocyclyalkyl having 1-4 heteroatoms selected from oxygen, nitrogen, or sulfur, wherein said 3- to 6-membered saturated or partially unsaturated monocyclic carbocyclyl, 3- to 6-membered saturated or partially unsaturated monocyclic heterocyclyl having 1-2 heteroatoms selected from oxygen, nitrogen, or sulfur, and 3- to 10-membered heterocyclyalkyl having 1-4 heteroatoms selected from oxygen, nitrogen, or sulfur, are optionally substituted with one or more R 65 ;

R 60a is selected from H and C 1-6 alkyl; or two R 60a groups are taken together with their intervening atoms to form a 3- to 6-membered heterocyclyl having 1-2 heteroatoms selected from oxygen, nitrogen, or sulfur;

R 60b is 5- or 6-membered monocyclic heterocyclyl;

each R 65 is independently selected from C 1-6 alkyl, —OR 65a , —N(R 65a ) 2 , —C(O) 2 R 65a , —S(O) 2 R 65b , and —S(O) 2 (NR 65a ) 2 ;

R 65a is selected from H and C 1-6 alkyl; and

R 65b is C 1-6 alkyl.

2. The compound of claim 1 , wherein R 1 is thiazolyl and R 10 is a C 1-6 aliphatic optionally substituted with one or more R 15 , wherein R 15 is halogen.

3. The compound of claim 1 , wherein R 2 is hydrogen.

4. The compound of claim 3 , wherein R 3 is hydrogen or C 1-6 aliphatic optionally substituted with hydroxyl.

5. The compound of claim 3 , wherein R 3 is —C(O)N(R) 2 , —C(O)N(R) 2 , —C(O)OR, or C 1-6 aliphatic optionally substituted with hydroxyl.

6. The compound of claim 4 , wherein R 4 is halogen, —OR, —SR, —N(R) 2 , —C(O)R, —C(O)OR, —S(O)R, —S(O) 2 R, —C(O)N(R) 2 , —SO 2 N(R) 2 , —OC(O)R, —N(R)C(O)R, —N(R)C(O)OR, —N(R)SO 2 R, —OC(O)N(R) 2 , or C 1-6 aliphatic optionally substituted with one or more R 40 .

7. The compound of claim 3 , wherein R 3 and R 4 , together with their intervening atoms, form fused Ring A optionally substituted with one or more R 40 .

8. The compound of claim 1 , wherein R 5 is hydrogen.

9. The compound of claim 1 , wherein R 6 is selected from H, phenyl, 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclyl, 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 1-2 heteroatoms selected from oxygen, nitrogen, or sulfur, and 5- to 6-membered heteroaryl having 1-4 heteroatoms selected from oxygen, nitrogen, or sulfur, wherein said phenyl, 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclyl, 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 1-2 heteroatoms selected from oxygen, nitrogen, or sulfur, 7- to 10-membered bicyclic heterocyclyl having 1-4 heteroatoms selected from oxygen, nitrogen, or sulfur, and 5- to 6-membered heteroaryl having 1-4 heteroatoms selected from oxygen, nitrogen, or sulfur, are optionally substituted with one or more R 60 .

10. The compound of claim 1 , wherein the compound is of formula IV-b, V-b, VI-b, VII-b or VII-e, or a pharmaceutically acceptable salt thereof:

11. The compound of claim 1 , wherein the compound is selected from one of the following compounds, or a pharmaceutically acceptable salt thereof:

12. A pharmaceutical composition comprising a compound of claim 1 , and a pharmaceutically acceptable excipient.

13. The compound of claim 10 , wherein R 2 in formula IV-b, V-b, or VI-b is hydrogen; R 3 in formula IV-b, V-b or VII-b is hydrogen, methyl or hydroxymethyl; R 4 in formula IV-b is C 1-6 aliphatic optionally substituted with one or more R 40 , wherein R 40 is halogen; or R 3 and R 4 , in formula IV-b, together with their intervening atoms, form fused Ring A optionally substituted with one or more R 40 , wherein ring A is fused 5- to 7-membered monocyclic carbocycle.

14. The compound of claim 13 , wherein R 6 is selected from the following:

15. The compound of claim 14 , wherein the compound is of formula VII-b, or VII-e, or a pharmaceutically acceptable salt thereof:

16. A compound selected from:

5-(tert-butyl)-N-(2-methyl-4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzyl)picolinamide,

4-(tert-butyl)-N-(2-methyl-4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzyl)benzamide,

N-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2-(trifluoromethyl)benzyl)-4-(tert-butyl)benzamide,

N-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2-(trifluoromethyl)benzyl)-5-(tert-butyl)picolinamide,

5-(tert-butyl)-N-(2-chloro-4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzyl)picolinamide,

5-(tert-butyl)-N-(2-cyano-4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzyl)picolinamide,

5-(tert-butyl)-N-(2-carbamoyl-4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzyl)picolinamide,

4-(tert-butyl)-N-(2-cyano-4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzyl)benzamide,

4-(tert-butyl)-N-(2-carbamoyl-4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzyl)benzamide,

4-(tert-butyl)-N-(2-ethyl-4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzyl)benzamide,

5-(tert-butyl)-N-(2-ethyl-4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzyl)picolinamide,

tert-butyl 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzylcarbamate,

5-(tert-butyl)-N-(2-chloro-5-fluoro-4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzyl)picolinamide,

N-(6-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-4-(tert-butyl)benzamide,

N-(6-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-5-(tert-butyl)picolinamide,

N-(6-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide,

N-(6-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-4,5,6,7-tetrahydrobenzo[d]thiazole-2-carboxamide,

5-(tert-butyl)-N-(4-(6-(1-(dimethylcarbamoyl)-1,2,3,6-tetrahydropyridin-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-4-yl)-2-methylbenzyl)thiazole-2-carboxamide,

2-(tert-butyl)-N-(4-(6-(1-(dimethylcarbamoyl)-1,2,3,6-tetrahydropyridin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2-methylbenzyl)thiazole-5-carboxamide,

methyl 4-(4-(4-((2-(tert-butyl)thiazole-5-carboxamido)methyl)-3-methylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-6-yl)benzoate,

2-(tert-butyl)-N-(4-(6-(1,1-dioxido-3,6-dihydro-2H-thiopyran-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2-methylbenzyl)thiazole-5-carboxamide,

2-(tert-butyl)-N-(4-(6-(1,1-dioxido-3,6-dihydro-2H-thiopyran-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-4-yl)-2-methylbenzyl)thiazole-5-carboxamide,

2-(tert-butyl)-N-(4-(6-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-4-yl)-2-methylbenzyl)thiazole-5-carboxamide,

2-(tert-butyl)-N-(4-(6-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-5-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-yl)-2-methylbenzyl)thiazole-5-carboxamide,

2-(tert-butyl)-N-(2-methyl-4-(6-(1-methylpiperidin-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-4-yl)benzyl)thiazole-5-carboxamide,

2-(tert-butyl)-N-(2-methyl-4-(6-(1-methyl-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzyl)thiazole-5-carboxamide,

2-(tert-butyl)-N-(2-methyl-4-(7-methyl-6-(1-methyl-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzyl)thiazole-5-carboxamide,

2-(tert-butyl)-N-(4-(6-(1,3-dimethyl-1H-pyrazol-4-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2-methylbenzyl)thiazole-5-carboxamide,

2-(tert-butyl)-N-(1-(4-(6-(1,1-dioxido-3,6-dihydro-2H-thiopyran-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-4-yl)phenyl)-2-hydroxyethyl)thiazole-5-carboxamide,

2-(tert-butyl)-N-(1-(4-(6-(1,1-dioxido-3,6-dihydro-2H-thiopyran-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl)-2-hydroxyethyl)thiazole-5-carboxamide,

2-(tert-butyl)-N-(2-hydroxy-1-(2-methyl-4-(6-(1-methyl-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl)ethyl)thiazole-5-carboxamide,

N-(2-hydroxy-1-(2-methyl-4-(6-(1-methyl-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl)ethyl)-6,7-dihydro-4H-thieno[3,2-c]pyran-2-carboxamide,

N-(2-methyl-4-(6-(1-methyl-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzyl)-6,7-dihydro-4H-thieno[3,2-c]pyran-2-carboxamide,

2-(tert-butyl)-N-(6-(6-(1-methyl-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)thiazole-5-carboxamide,

N-(6-(6-(1-methyl-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-6,7-dihydro-4H-thieno[3,2-c]pyran-2-carboxamide,

5-(tert-butyl)-N-(2-methyl-4-(6-(1-methyl-1H-pyrazol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-4-yl)benzyl)thiazole-2-carboxamide,

2-(tert-butyl)-N-(6-(6-(1-methyl-1H-pyrazol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)thiazole-5-carboxamide,

2-(tert-butyl)-N-(2-methyl-4-(5-methyl-6-(1-methyl-1H-pyrazol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-4-yl)benzyl)thiazole-5-carboxamide,

2-(tert-butyl)-N-(4-(6-(1,3-dimethyl-1H-pyrazol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-4-yl)-2-methylbenzyl)thiazole-5-carboxamide,

5-(tert-butyl)-N-(4-(6-(1-ethyl-1H-pyrazol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-4-yl)-2-methylbenzyl)thiazole-2-carboxamide,

N-(4-(6-(1H-pyrazol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-4-yl)-2-methylbenzyl)-5-(tert-butyl)thiazole-2-carboxamide,

N-(2-methyl-4-(6-(1-methyl-1H-pyrazol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-4-yl)benzyl)-6,7-dihydro-4H-thieno[3,2-c]pyran-2-carboxamide,

3-isopropoxy-N-(2-methyl-4-(6-(1-methyl-1H-pyrazol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-4-yl)benzyl)azetidine-1-carboxamide,

2-(tert-butyl)-N-(2-hydroxy-1-(2-methyl-4-(6-(1-methyl-1H-pyrazol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-4-yl)phenyl)ethyl)thiazole-5-carboxamide,

N-(2-hydroxy-1-(2-methyl-4-(6-(1-methyl-1H-pyrazol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-4-yl)phenyl)ethyl)-6,7-dihydro-4H-thieno[3,2-c]pyran-2-carboxamide,

2-(tert-butyl)-N-(1-(2-methyl-4-(6-(1-methyl-1H-pyrazol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-4-yl)phenyl)ethyl)thiazole-5-carboxamide,

2-(tert-butyl)-N-(2-methyl-4-(8-(4-methylpiperazin-1-yl)-7H-purin-6-yl)benzyl)thiazole-5-carboxamide,

2-(tert-butyl)-N-(2-methyl-4-(8-morpholino-7H-purin-6-yl)benzyl)thiazole-5-carboxamide,

2-(tert-butyl)-N-(4-(8-(4-(dimethylamino)piperidin-1-yl)-7H-purin-6-yl)-2-methylbenzyl)thiazole-5-carboxamide,

2-(tert-butyl)-N-(4-(8-(3-(dimethylamino)pyrrolidin-1-yl)-7H-purin-6-yl)-2-methylbenzyl)thiazole-5-carboxamide,

1-(6-(4-((2-(tert-butyl)thiazole-5-carboxamido)methyl)-3-methylphenyl)-7H-purin-8-yl)pyrrolidine-3-carboxylic acid,

1-(6-(4-((2-(tert-butyl)thiazole-5-carboxamido)methyl)-3-methylphenyl)-7H-purin-8-yl)piperidine-4-carboxylic acid,

2-(tert-butyl)-N-(4-(8-(3-(dimethylamino)azetidin-1-yl)-7H-purin-6-yl)-2-methylbenzyl)thiazole-5-carboxamide,

2-(tert-butyl)-N-(2-methyl-4-(8-(1-methylpiperidin-4-yl)-7H-purin-6-yl)benzyl)thiazole-5-carboxamide,

1-(6-(4-((2-(tert-butyl)thiazole-5-carboxamido)methyl)-3-methylphenyl)-7H-purin-8-yl)pyrrolidine-2-carboxylic acid,

N-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzyl)-5,6,7,8-tetrahydroisoquinoline-3-carboxamide,

N-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzyl)-5,6,7,8-tetrahydroquinoline-2-carboxamide,

N-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole-2-carboxamide,

N-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzyl)-2,3-dihydro-1H-indene-2-carboxamide,

N-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzyl)benzo[b]thiophene-2-carboxamide,

N-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzyl)-4,5,6,7-tetrahydrobenzo[d]thiazole-2-carboxamide,

N-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzyl)-5-chloro-4-(trifluoromethyl)picolinamide,

N-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxamide,

N-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide, N-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzyl)-4-(trifluoromethyl)benzamide,

N-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzyl)-6-(tert-butyl)nicotinamide,

N-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzyl)-5-(tert-butyl)picolinamide,

N-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzyl)isoindoline-2-carboxamide,

N-((5-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyridin-2-yl)methyl)-4-(tert-butyl)benzamide,

N-((5-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyridin-2-yl)methyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide,

N-((6-(1H-pyrrolo[2,3-b]pyridin-4-yl)pyridin-3-yl)methyl)-5-(tert-butyl)picolinamide,

N-((6-(1H-pyrrolo[2,3-b]pyridin-4-yl)pyridin-3-yl)methyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide,

(R)—N-(1-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl)ethyl)-4,5,6,7-tetrahydrobenzo[d]thiazole-2-carboxamide,

(S)—N-(1-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl)ethyl)-4,5,6,7-tetrahydrobenzo[d]thiazole-2-carboxamide,

2-(tert-butyl)-N-(2-methyl-4-(6-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzyl)thiazole-5-carboxamide hydrochloride,

N-(1-(2-methyl-4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl)ethyl)-4,5,6,7-tetrahydrobenzo[d]thiazole-2-carboxamide,

N-(1-(2-methyl-4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl)ethyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide,

N-(1-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2-(trifluoromethyl)phenyl)ethyl)-4,5,6,7-tetrahydrobenzo[d]thiazole-2-carboxamide,

N-(1-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2-(trifluoromethyl)phenyl)ethyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide,

(R)—N-(6-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide,

N-(7-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)isochroman-4-yl)-5-(tert-butyl)picolinamide,

N-(7-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)isochroman-4-yl)-4-(tert-butyl)benzamide,

N-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)benzyl)-4-(tert-butyl)benzamide,

N-(2-methyl-4-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)benzyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide,

(R)—N-(6-(1H-Pyrazolo[3,4-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide,

(S)—N-(6-(1H-Pyrazolo[3,4-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide,

N-(6-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-4-(tert-butyl)benzamide,

(S)—N-(6-(7H-Pyrrolo[2,3-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide,

N-(6-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-4-chloro-3-fluorobenzamide,

N-(6-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-3-fluoro-4-(trifluoromethyl)benzamide,

N-(6-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-3-chloro-4-(trifluoromethyl)benzamide,

N-(6-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-3,4-dichlorobenzamide,

N-(6-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-5,6-dihydro-4H-cyclopenta[b]thiophene-2-carboxamide,

N-(6-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-4,5-dimethylthiazole-2-carboxamide,

N-(6-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-4-isopropylthiazole-2-carboxamide,

N-(6-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-4-(trifluoromethyl)benzamide,

N-(6-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-1,2,3,4-tetrahydro naphthalen-1-yl) -4-(tert-butyl) thiazole-2-carboxamide,

(R)—N-(6-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-4-(tert-butyl)thiazole-2-carboxamide,

(R)—N-(6-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-4-(tert-butyl)thiazole-2-carboxamide,

N-(6-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-1-methyl-1H-benzo[d]imidazole-2-carboxamide,

2-(tert-butyl)-N-(2-methyl-4-(6-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzyl)thiazole-5-carboxamide,

N-(6-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-5-(tert-butyl)-1,3,4-thiadiazole-2-carboxamide,

N-(6-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-4-(tert-butyl)cyclohexanecarboxamide,

trans-N—((R)-6-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-4-(trifluoromethyl)cyclohexanecarboxamide,

N-(6-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)benzo[d]thiazole-2-carboxamide,

N-(6-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide,

N-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-2-(trifluoromethyl)benzyl)-4,5,6,7-tetrahydrobenzo[d]thiazole-2-carboxamide,

N-((3-fluoro-5-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)pyridin-2-yl)methyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide,

N-((3-fluoro-5-(1H-pyrazolo[3,4-b]pyridin-4-yl)pyridin-2-yl)methyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide,

4-(tert-butyl)-N-(4-(6-(4-(morpholine-4-carbonyl)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzyl)benzamide,

2-(tert-butyl)-N-(1-(2-methyl-4-(6-(1-methyl-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl)ethyl)thiazole-5-carboxamide,

N-(1-(2-methyl-4-(6-(1-methyl-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl)ethyl)-6,7-dihydro-4H-thieno[3,2-c]pyran-2-carboxamide,

2-(tert-butyl)-N-(1-(4.-(6-(1-methyl-1H-pyrazol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-4-yl)phenyl)ethyl)thiazole-5-carboxamide,

2-(tert-butyl)-N-(2-methyl-4-(5H-pyrrolo[3,2-d]pyrimidin-4-yl)benzyl)thiazole-5-carboxamide,

N-(2-methyl-4-(5H-pyrrolo[3,2-d]pyrimidin-4-yl)benzyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide,

N-((4-methyl-6-(1H-pyrazolo[3,4-b]pyridin-4-yl)pyridin-3-yl)methyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide,

N-((2-methyl-6-(1H-pyrazolo[3,4-b]pyridin-4-yl)pyridin-3-yl)methyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide,

4,5,6,7-tetrahydro-benzothiazole-2-carboxylic acid 2-methyl-4-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-benzylamide,

N-(6-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)benzo[b]thiophene-2-carboxamide,

N-(1-(2-methyl-4-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)phenyl)ethyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide,

N-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2-(trifluoromethyl)benzyl)-4,5,6,7-tetrahydrobenzo[d]thiazole-2-carboxamide,

N-(1-(2-methyl-4-(5H-pyrrolo[3,2-d]pyrimidin-4-yl)phenyl)ethyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide,

4-(6-(4-((2-(tert-butyl)thiazole-5-carboxamido)methyl)-3-methylphenyl)-7H-purin-8-yl)morpholine-2-carboxylic acid,

N-((3-methyl-5-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)pyridin-2-yl)methyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide,

N-((3-methyl-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)pyridin-2-yl)methyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide,

N-(1-(2-methyl-4-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)phenyl)ethyl)-4,5,6,7-tetrahydrobenzo[d]thiazole-2-carboxamide,

2-(tert-butyl)-N-(1-(2-methyl-4-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)phenyl)ethyl)thiazole-5-carboxamide,

N-(6-(5H-pyrrolo[3,2-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-2-(tert-butyl)thiazole-5-carboxamide,

N-(6-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-5,6-dihydro-4H-cyclopenta[d]thiazole-2-carboxamide,

N-(6-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-5-(tert-butyl)picolinamide,

N-(1-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)phenyl)-2-hydroxyethyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide,

2-(tert-butyl)-N-(2-methyl-4-(2-(4-methylpiperazin-1-yl)thiazolo[4,5-d]pyrimidin-7-yl)benzyl)thiazole-5-carboxamide,

2-(tert-butyl)-N-(1-(2-methyl-4-(5H-pyrrolo[3,2-d]pyrimidin-4-yl)phenyl)ethyl)thiazole-5-carboxamide,

N-(1-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-2-(trifluoromethyl)phenyl)ethyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide,

N-(6-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-6,6-dimethyl-4,5,6,7-tetrahydrobenzo[d]thiazole-2-carboxamide,

N-(6-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-4,5,6,7-tetrahydrobenzo[d]thiazole-2-carboxamide,

2-(6-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-6-cyclopropyl-8-fluoroisoquinolin-1(2H)-one,

N-((3-methyl-5-(1H-pyrazolo[3,4-b]pyridin-4-yl)pyridin-2-yl)methyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide,

N-((3-methyl-5-(5H-pyrrolo[3,2-d]pyrimidin-4-yl)pyridin-2-yl)methyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide,

N-(6-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-6-(tert-butyl)nicotinamide,

N-(1-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)phenyl)propyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide,

(R)—N-(3-(1H-pyrazolo[3,4-b]pyridin-4-yl)-5,6,7,8-tetrahydroquinolin-8-yl)-2-(tert-butyl)thiazole-5-carboxamide,

N-(1-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-2-(trifluoromethyl)phenyl)ethyl)-4,5,6,7-tetrahydrobenzo[d]thiazole-2-carboxamide,

N-(6-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-5-(trifluoromethyl)picolinamide,

N-(1-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)phenyl)-2-methylpropyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide,

N-(6-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-4-(tert-butyl)picolinamide,

N-(1-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)phenyl)-2-amino-2-oxoethyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide,

(S)—N-(3-(1H-pyrazolo[3,4-b]pyridin-4-yl)-5,6,7,8-tetrahydroquinolin-8-yl)-2-(tert-butyl)thiazole-5-carboxamide,

N-((3-methyl-5-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyridin-2-yl)methyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide,

N-(5-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl)-4-(tert-butyl)benzamide,

1-(tert-butyl)-N-(6-(6-(1-methyl-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-1H-pyrazole-4-carboxamide,

3-(tert-butyl)-N-(6-(6-(1-methyl-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)pyrrolidine-1-carboxamide,

3-isopropoxy-N-(6-(6-(1-methyl-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)azetidine-1-carboxamide,

3-(tert-butoxy)-N-(6-(6-(1-methyl-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)azetidine-1-carboxamide,

1-(tert-butyl)-N-(2-(6-(1-methyl-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-yl)-1H-pyrazole-4-carboxamide,

2-(tert-butyl)-N-(2-(6-(1-methyl-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-yl)thiazole-5-carboxamide,

3-(tert-butyl)-N-(2-(6-(1-methyl-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-yl)pyrrolidine-1-carboxamide,

3-isopropoxy-N-(2-(6-(1-methyl-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-yl)azetidine-1-carboxamide, and

3-(tert-butoxy)-N-(2-(6-(1-methyl-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-yl)azetidine-1-carboxamide,

or a pharmaceutically acceptable salt thereof.