US 12,202,813 B2
Process for preparing 6-(1-acryloylpiperidin-4-yl)-2-(4-phenoxyphenyl)nicotinamide
Xiangyang Chen, Beijing (CN)
Assigned to Beijing InnoCare Pharma Tech Co., Ltd, Beijing (CN)
Filed by BEIJING INNOCARE PHARMA TECH CO., LTD., Beijing (CN)
Filed on Aug. 20, 2021, as Appl. No. 17/407,340.
Application 17/407,340 is a continuation of application No. PCT/CN2020/076387, filed on Feb. 24, 2020.
Claims priority of provisional application 62/810,305, filed on Feb. 25, 2019.
Prior Publication US 2021/0380555 A1, Dec. 9, 2021
Int. Cl. C07D 401/04 (2006.01)
CPC C07D 401/04 (2013.01) 5 Claims
 
1. A method for preparing 6-(1-acryloylpiperidin-4-yl)-2-(4-phenoxyphenyl) nicotinamide (Compound I), comprising:
(a) heating a mixture of INA, SMC, and a first palladium-containing catalyst at 60-140° C. to obtain INB,

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wherein PG is a protecting group of tert-butyloxycarbonyl;
(b) hydrogenating INB under H2 in the presence of a second palladium-containing catalyst to obtain INC;

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(c) adding HCl gas to deprotect INC and obtain IND-HCl salt in a solid form;

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(d) reacting the IND-HCl salt with acryloyl chloride or 3-chloropropanoyl chloride under a basic condition to obtain 6-(1-acryloylpiperidin-4-yl)-2-(4-phenoxyphenyl) nicotinamide

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