US 12,421,230 B2
Tricyclic heteroaryl compounds useful as IRAK4 inhibitors
Saleem Ahmad, Wall, NJ (US); and Lidet A. Negash, Plainsboro, NJ (US)
Assigned to Bristol-Myers Squibb Company, Princeton, NJ (US)
Appl. No. 17/792,837
Filed by BRISTOL-MYERS SQUIBB COMPANY, Princeton, NJ (US)
PCT Filed Feb. 2, 2021, PCT No. PCT/US2021/016126
§ 371(c)(1), (2) Date Jul. 14, 2022,
PCT Pub. No. WO2021/158498, PCT Pub. Date Aug. 12, 2021.
Claims priority of provisional application 62/969,406, filed on Feb. 3, 2020.
Prior Publication US 2023/0114683 A1, Apr. 13, 2023
Int. Cl. C07D 471/04 (2006.01); C07D 471/14 (2006.01)
CPC C07D 471/04 (2013.01) [C07D 471/14 (2013.01)] 9 Claims
 
1. A compound of Formula (I) or Formula (II):

OG Complex Work Unit Chemistry
or a salt thereof, wherein:
X is CR3a or N;
R1 is:
(i) —C(O)NRxR1a; or
(ii) pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, oxadiazolyl, triazolyl, or thiadiazolyl, each substituted with zero to 2 R1b;
R1a is:
(i) C1-6 alkyl substituted with zero to 6 Rw; or
(ii) —(CRxRx)0-3R1c;
each Rw is independently F, Cl, —CN, —OH, —OCH3, —NRxRx, —NRxC(O)(C1-3 alkyl), —NRxC(O)(C3-6 cycloalkyl), or C3-6 cycloalkyl;
each R1b is independently —CRxRx(C3-6 cycloalkyl), tetrahydrofuranyl, pyrrolidinyl, tetrahydropyranyl, piperidinyl, piperazinyl, morpholinyl, or C1-6 alkyl substituted with zero to 6 Rw;
R1c is C3-6 cycloalkyl, oxetanyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, dioxidotetrahydrothiophenyl, dioxidothiomorpholinyl, isoxazolyl, oxazolyl, thiazolyl, oxadiazolyl, triazolyl, or tetrazolyl, each substituted with zero to 3 substituents independently selected from F, Cl, —CN, —OH, —NRxRx, C1-3 alkyl, C1-3 fluoroalkyl, C1-3 hydroxyalkyl, —NRxC(O)(C1-3 alkyl), —NRxC(O)O(C1-3 alkyl), and —S(O)2(C1-2 alkyl);
R2 is:
(i) hydrogen;
(ii) C1-6 alkyl substituted with zero to 4 substituents independently selected from F, Cl, —OH, —CN, C3-6 cycloalkyl, and dimethoxyphenyl; or
(ii) a cyclic group selected from C3-6 cycloalkyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, pyrazolyl, and thiazolyl, wherein said cyclic group is substituted with zero to 3 substituents independently selected from F, Cl, —OH, —CN, C1-2 alkyl, C1-2 fluoroalkyl, C1-2 hydroxyalkyl, and —S(O)2(C1-2 alkyl);
R3 is —CN, —C(O)NRxRx, or a cyclic group selected from phenyl, pyrazolyl, imidazolyl, triazolyl, pyridinyl, pyridinonyl, and pyrimidinyl, each cyclic group substituted with zero to 3 substituents selected from F, Cl, —OH, —CN, C1-2 alkyl, —CF3, and —CH2OH;
R3a is hydrogen or R3;
each Rx is hydrogen or —CH3; and
n is zero, 1, or 2.