Heteroaryl substituted aminopyridine compounds

1. A compound of Formula (I)

or a salt thereof, wherein:

HET is a heteroaryl selected from imidazo[1,2-b]pyridazinyl and pyrazolo[1,5-a] pyrimidinyl, wherein said heteroaryl is attached to the pyridinyl group in the compound of Formula (I) by a carbon ring atom in said heteroaryl and wherein said heteroaryl is substituted with zero to 2 R b ;

A is pyrazolyl, imidazolyl, or triazolyl, each substituted with zero or 1 R a ;

R 3 is:

(i) —CH 2 CH 3 , —CH(CH 3 ) 2 , —CH 2 CHF 2 , —CH(CH 3 )CH 2 OH, oxetanyl, tetrahydropyranyl, or C 3-5 cycloalkyl substituted with zero to 2 F; or

(ii) pyrazolyl substituted with zero to 2 substituents independently selected from C 1-3 alkyl, C 1-3 hydroxyalkyl, C 1-3 fluoroalkyl, oxetanyl, tetrahydrofuranyl, and tetrahydropyranyl;

R a is:

(i) F, Cl, —OH, —CN, C 1-6 alkyl, C 1-4 fluoroalkyl, C 1-4 cyanoalkyl, or C 1-6 hydroxyalkyl; or

(ii) C 3-6 cycloalkyl, azetidinyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, piperazinyl, pyrrolyl, pyrrolidinonyl, morpholinyl, pyrrolidinyl, phenyl, pyrazolyl, imidazolyl, pyridinyl, or pyrimidinyl, each substituted with zero to 4 substituents independently selected F, —CN, —OH, —NR y R y , C 1-3 alkyl, C 1-3 fluoroalkyl, —CH(phenyl) 2 , —O(C 1-4 alkyl), —C(O)(C 1-4 alkyl), —C(O)(C 1-4 deuteroalkyl), —C(O)(C 3-6 cycloalkyl), —C(O)O(C 1-4 alkyl), —C(O)NR y R y , —C(O)(phenyl), —C(O)(pyridinyl), —C(O)CH 2 (C 3-6 cycloalkyl), —NHC(O)CH 3 , —NHC(O)OCH 3 , —NHC(O)OC(CH 3 ) 3 , —S(O) 2 (C 1-3 alkyl), and —OS(O) 2 (C 1-3 alkyl);

each R b is independently selected from F, Cl, —CN, —NH 2 , —CH 3 , —OCH 3 , and cyclopropyl;

and each R y is independently H or C 1-3 alkyl.

2. The compound according to claim 1 or a salt thereof, wherein:

HET is a heteroaryl selected from imidazo[1,2-b]pyridazinyl and pyrazolo[1,5-a] pyrimidinyl, wherein said heteroaryl is attached to the pyridinyl group in the compound of Formula (I) by a carbon ring atom in said heteroaryl and wherein said heteroaryl is substituted with zero to 2 R b ;

A is pyrazolyl, imidazolyl, or triazolyl, each substituted with zero or 1 R a ;

R 3 is:

(i) —CH 2 CH 3 , —CH(CH 3 ) 2 , —CH 2 CHF 2 , —CH(CH 3 )CH 2 OH, cyclopropyl, oxetanyl, or tetrahydropyranyl; or

(ii) pyrazolyl substituted with zero to 2 substituents independently selected from C 1-3 alkyl, C 1-3 hydroxyalkyl, C 1-3 fluoroalkyl, oxetanyl, tetrahydrofuranyl, and tetrahydropyranyl;

R a is:

(i) F, Cl, —OH, —CN, C 1-6 alkyl, C 1-4 fluoroalkyl, C 1-4 cyanoalkyl, or C 1-6 hydroxyalkyl; or

(ii) C 3-6 cycloalkyl, azetidinyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, piperazinyl, pyrrolyl, pyrrolidinonyl, morpholinyl, pyrrolidinyl, phenyl, pyrazolyl, imidazolyl, pyridinyl, or pyrimidinyl, each substituted with zero to 4 substituents independently selected F, —CN, —OH, —NR y R y , C 1-3 alkyl, C 1-3 fluoroalkyl, —CH(phenyl) 2 , —O(C 1-4 alkyl), —C(O)(C 1-4 alkyl), —C(O)(C 1-4 deuteroalkyl), —C(O)(C 3-6 cycloalkyl), —C(O)O(C 1-4 alkyl), —C(O)NR y R y , —C(O)(phenyl), —C(O)(pyridinyl), —C(O)CH 2 (C 3-6 cycloalkyl), —NHC(O)CH 3 , —NHC(O)OCH 3 , —NHC(O)OC(CH 3 ) 3 , —S(O) 2 (C 1-3 alkyl), and —OS(O) 2 (C 1-3 alkyl);

each R b is independently selected from F, Cl, —CN, —NH 2 , —CH 3 , —OCH 3 , and cyclopropyl;

and each R y is independently H or C 1-3 alkyl.

3. The compound according to claim 1 or a salt thereof, wherein:

HET is a heteroaryl selected from imidazo[1,2-b]pyridazinyl and pyrazolo[1,5-a] pyrimidinyl, wherein said heteroaryl is attached to the pyridinyl group in the compound of Formula (I) by a carbon ring atom in said heteroaryl and wherein said heteroaryl is substituted with zero to 1 R b ;

A is pyrazolyl or triazolyl, each substituted with zero or 1 R a ;

R 3 is —CH(CH 3 ) 2 , cyclopropyl, difluorocyclobutyl, fluorocyclopentyl, oxetanyl, tetrahydropyranyl, or 2,2-difluoroethyl pyrazolyl;

R a is —OH, —CH 3 , —CH 2 CH 2 CH 3 , —CH 2 CF 3 , —C(CH 3 ) 2 OH, —CH 2 C(CH 3 ) 2 OH, —CH 2 CH 2 C(CH 3 ) 2 OH, tetrahydropyranyl, acetylazetidinyl, or

and R b is Cl or —CN.

4. The compound according to claim 1 or a salt thereof, wherein:

HET is a heteroaryl selected from imidazo[1,2-b]pyridazinyl and pyrazolo[1,5-a] pyrimidinyl, wherein said heteroaryl is attached to the pyridinyl group in the compound of Formula (I) by a carbon ring atom in said heteroaryl and wherein said heteroaryl is substituted with zero to 1 R b ;

A is pyrazolyl or triazolyl, each substituted with zero or 1 R a ;

R 3 is —CH(CH 3 ) 2 , cyclopropyl, or 2,2-difluoroethyl pyrazolyl;

R a is —OH, —CH 3 , —CH 2 CH 2 CH 3 , —CH 2 CF 3 , —C(CH 3 ) 2 OH, —CH 2 C(CH 3 ) 2 OH, —CH 2 CH 2 C(CH 3 ) 2 OH, tetrahydropyranyl, acetylazetidinyl, or

and R b is Cl or —CN.

5. The compound according to claim 1 or a salt thereof, wherein:

A is

6. The compound according to claim 1 or a salt thereof, wherein:

A is

7. The compound according to claim 1 or a salt thereof, wherein HET is:

8. The compound according to claim 1 or a salt thereof, wherein:

HET is

R 3 is —CH(CH 3 ) 2 , cyclopropyl,

and

R b is Cl or —CN.

9. The compound according to claim 1 or a salt thereof, wherein A is pyrazolyl.

10. The compound according to claim 1 or a salt thereof, wherein A is triazolyl.

11. The compound according to claim 1 or a salt thereof, wherein said compound is selected from: 3-(5-(4-(2-hydroxypropan-2-yl)-1H-pyrazol-1-yl)-4-(isopropylamino) pyridin-2-yl) pyrazolo[1,5-a]pyrimidine-6-carbonitrile (1); 2-(7-chloroimidazo[1,2-b] pyridazin-3-yl)-N-isopropyl-5-(4-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-1-yl)pyridin-4-amine (2); 3-(4-(isopropylamino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl) pyridin-2-yl)imidazo[1,2-b]pyridazine-7-carbonitrile (3); 1-(4-(6-(7-chloroimidazo[1,2-b] pyridazin-3-yl)-4-(isopropylamino)pyridin-3-yl)-1H-pyrazol-1-yl)-2-methylpropan-2-ol (4); 3-(5-(1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl)-4-(isopropylamino)pyridin-2-yl)imidazo[1,2-b]pyridazine-7-carbonitrile (5); 3-(4-(isopropylamino)-5-(1-propyl-1H-pyrazol-4-yl)pyridin-2-yl)imidazo[1,2-b]pyridazine-7-carbonitrile (6); 2-(7-chloroimidazo[1,2-b]pyridazin-3-yl)-N-isopropyl-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-amine (7); 3-(4-(isopropylamino)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)imidazo[1,2-b]pyridazine-7-carbonitrile (8); 2-(7-chloroimidazo[1,2-b] pyridazin-3-yl)-N-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)-5-(1-propyl-1H-pyrazol-4-yl) pyridin-4-amine (9); 3-(4-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)amino)-5-(1-propyl-1H-pyrazol-4-yl)pyridin-2-yl)imidazo[1,2-b]pyridazine-7-carbonitrile (10); 2-(6-chloropyrazolo[1,5-a]pyrimidin-3-yl)-N-isopropyl-5-(4-propyl-1H-1,2,3-triazol-1-yl) pyridin-4-amine (11); 3-(4-(isopropylamino)-5-(4-propyl-1H-1,2,3-triazol-1-yl)pyridin-2-yl)pyrazolo[1,5-a]pyrimidine-6-carbonitrile (12); 4-(1-(6-(6-chloropyrazolo[1,5-a] pyrimidin-3-yl)-4-(isopropylamino)pyridin-3-yl)-1H-1,2,3-triazol-4-yl)-2-methylbutan-2-ol (13); 4-(1-(6-(6-chloropyrazolo[1,5-a]pyrimidin-3-yl)-4-(oxetan-3-ylamino)pyridin-3-yl)-1H-1,2,3-triazol-4-yl)-2-methylbutan-2-ol (14); 3-(4-(isopropylamino)-5-(4-propyl-1H-1,2,3-triazol-1-yl)pyridin-2-yl) imidazo[1,2-b]pyridazine-7-carbonitrile (15); 3-(4-(isopropylamino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)pyridin-2-yl) imidazo[1,2-b]pyridazine-7-carbonitrile (16); 3-(5-(1-(1-acetylazetidin-3-yl)-1H-1,2,3-triazol-4-yl)-4-(isopropylamino)pyridin-2-yl)imidazo [1,2-b]pyridazine-7-carbonitrile (17); 3-(4-(cyclopropylamino)-5-(1-propyl-1H-1,2,3-triazol-4-yl)pyridin-2-yl)imidazo [1,2-b]pyridazine-7-carbonitrile (18); 2-(7-chloroimidazo[1,2-b]pyridazin-3-yl)-N-cyclopropyl-5-(1-propyl-1H-1,2,3-triazol-4-yl)pyridin-4-amine (19); 2-(7-chloroimidazo [1,2-b]pyridazin-3-yl)-N-isopropyl-5-(1-propyl-1H-1,2,3-triazol-4-yl)pyridin-4-amine (20); (3R)-methyl 4-(4-(6-(7-chloroimidazo[1,2-b]pyridazin-3-yl)-4-(cyclopropylamino) pyridin-3-yl)-1H-1,2,3-triazol-1-yl)-3-hydroxy-3-methylpiperidine-1-carboxylate (21); 3-(5-(4-(3-hydroxy-3-methylbutyl)-1H-1,2,3-triazol-1-yl)-4-(isopropylamino)pyridin-2-yl) imidazo[1,2-b]pyridazine-7-carbonitrile (22); 4-(1-(6-(6-chloropyrazolo[1,5-a] pyrimidin-3-yl)-4-((tetrahydro-2H-pyran-4-yl)amino)pyridin-3-yl)-1H-1,2,3-triazol-4-yl)-2-methylbutan-2-ol (23); 3-(4-((3,3-difluorocyclobutyl)amino)-5-(4-(3-hydroxy-3-methylbutyl)-1H-1,2,3-triazol-1-yl)pyridin-2-yl)pyrazolo[1,5-a]pyrimidine-6-carbonitrile (24); 3-(4-(((1S,3 S)-3-fluorocyclopentyl)amino)-5-(4-(3-hydroxy-3-methylbutyl)-1H-1,2,3-triazol-1-yl)pyridin-2-yl)pyrazolo[1,5-a]pyrimidine-6-carbonitrile (25); 3-(5-(4-(3-hydroxy-3-methylbutyl)-1H-1,2,3-triazol-1-yl)-4-(oxetan-3-ylamino)pyridin-2-yl) pyrazolo[1,5-a]pyrimidine-6-carbonitrile (26); 3-(5-(1-(3-hydroxy-3-methylbutyl)-1H-pyrazol-4-yl)-4-(isopropylamino)pyridin-2-yl) imidazo[1,2-b]pyridazine-7-carbonitrile (27); 3-(4-(isopropylamino)-5-(5-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-3-yl)pyridin-2-yl)imidazo[1,2-b]pyridazine-7-carbonitrile (28); and 3-(5-(5-(3-hydroxy-3-methylbutyl)-1H-pyrazol-3-yl)-4-((tetrahydro-2H-pyran-4-yl)amino)pyridin-2-yl)pyrazolo[1,5-a] pyrimidine-6-carbonitrile (29).

12. A pharmaceutical composition comprising one or more compounds according to claim 1 and a pharmaceutically acceptable carrier or diluent.