US 12,421,229 B2
Hydropyrido[1,2-α]pyrazine compounds for the treatment of autoimmune disease
Jianguo Chen, Shanghai (CN); Fabian Dey, Zurich (CH); Hongtao Xu, Shanghai (CN); Weixing Zhang, Shanghai (CN); and Wei Zhu, Shanghai (CN)
Assigned to Hoffmann-La Roche Inc., Little Falls, NJ (US)
Appl. No. 17/780,161
Filed by Hoffmann-La Roche Inc., Little Falls, NJ (US)
PCT Filed Dec. 1, 2020, PCT No. PCT/EP2020/083996
§ 371(c)(1), (2) Date May 26, 2022,
PCT Pub. No. WO2021/110614, PCT Pub. Date Jun. 10, 2021.
Claims priority of application No. PCT/CN2019/122716 (WO), filed on Dec. 3, 2019.
Prior Publication US 2023/0022297 A1, Jan. 26, 2023
Int. Cl. C07D 471/04 (2006.01); C07D 519/00 (2006.01)
CPC C07D 471/04 (2013.01) [C07D 519/00 (2013.01)] 13 Claims
 
1. A compound of formula (I),

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wherein

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R1 is
wherein R4 is C1-6alkyl, C1-6alkoxy, haloC1-6alkyl, halogen, nitro or cyano; R4a is C1-6alkyl or C3-7cycloalkyl; R5, R5a and R5b are independently selected from H and deuterium; and R6 is H or halogen;
R2 is C1-6alkyl; and
R3 is ((amino (C1-6alkoxy) pyrrolidinyl) phenyl) azetidinyl, (amino (C1-6alkoxy) pyrrolidinyl) pyridinyl, (amino(C1-6alkoxy) pyrrolidinyl) pyridinyloxy, (amino-1,4-oxazepanyl) pyridinyl, (aminoazetidinyl) pyridinyl, (morpholinylC1-6alkyl) phenyl, (morpholinylC1-6alkyl) phenylamino, (piperazinylphenyl) azetidinyl, (piperazinylphenyl) C1-6alkylamino, aminohalopyrrolidinyl, morpholinylphenyl, morpholinylphenylamino, piperazinylphenyl, piperazinylpyridinyl, piperazinylpyridinyloxy, piperazinylpyrimidinyloxy or pyridinylpiperazinyl;
or a pharmaceutically acceptable salt thereof.
 
9. A process for the preparation of a compound according to claim 1, comprising any one of the following steps:
a) Buchwald-Hartwig amination reaction between a compound of formula (VIII),

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and amine (V),

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b) reductive amination of a compound of formula (IV),

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with amine (V),

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c) Buchwald-Hartwig amination reaction between a compound of formula (XIV),

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and amine (V),

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d) Buchwald-Hartwig amination reaction between a compound of formula (XVIII),

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and amine (V),

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wherein:
X is halogen;
R7 is H;
R8 is heterocyclylheteroaryl, heterocyclylC1-6alkylheteroaryl, heterocyclylheteroarylC1-6alkyl, heterocyclylC1-6alkylaryl, or heterocyclylarylC1-6alkyl;
or R7 and R8 together with the nitrogen they are attached to form a heterocyclyl;
W is heteroaryl or aryl; and
R1 and R2 are defined as in claim 1.