US 12,304,914 B2
Pyrazolo[3,4-d]pyrrolo[1,2-b]pyridazinyl compounds useful as IRAK4 inhibitors
Hong Wu, New Hope, PA (US); and John Hynes, Washington Crossing, PA (US)
Assigned to Bristol-Myers Squibb Company, Princeton, NJ (US)
Appl. No. 17/627,967
Filed by BRISTOL-MYERS SQUIBB COMPANY, Princeton, NJ (US)
PCT Filed Jul. 16, 2020, PCT No. PCT/US2020/042252
§ 371(c)(1), (2) Date Jan. 18, 2022,
PCT Pub. No. WO2021/011727, PCT Pub. Date Jan. 21, 2021.
Claims priority of provisional application 62/875,567, filed on Jul. 18, 2019.
Prior Publication US 2022/0267335 A1, Aug. 25, 2022
Int. Cl. C07D 487/04 (2006.01)
CPC C07D 487/04 (2013.01) 8 Claims
 
1. A compound of Formula (I)

OG Complex Work Unit Chemistry
or a salt thereof, wherein:
R1 is —NHR1a or —NHCH2R1a;
R1a is C4-6 cycloalkyl, azetidinyl, pyrrolidinyl, piperidinyl, or azepanyl, each substituted with zero to 2 substituents independently selected from F, Cl, —OH, —CN, C1-3 alkyl, C1-2 fluoroalkyl, —C(O)(C1-3 alkyl), —C(O)O(C1-3 alkyl), and —NRxC(O)O(C1-3 alkyl);
R2 is:
(i) C1-6 alkyl substituted with zero to 4 substituents independently selected from F, Cl, —OH, and —CN; or
(ii) a cyclic group selected from C3-6 cycloalkyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, and pyrazolyl, wherein said cyclic group is substituted with zero to 3 substituents independently selected from F, —OH, —CN, C1-2 alkyl, C1-2 fluoroalkyl, and C1-2 hydroxyalkyl;
R3 is phenyl, pyrazolyl, imidazolyl, triazolyl, pyridinyl, pyridinonyl, or pyrimidinyl, each substituted with zero to 3 substituents selected from F, Cl, —OH, —CN, C1-2 alkyl, —CF3, and —CH2OH;
each R4 is independently F, Cl, —CH3, or —CN;
each Rx is hydrogen or —CH3; and
n is zero, 1, or 2.