Preparing 7-chloro-6-fluoro-1-[4-methyl-2-(propan-2-yl)pyridin-3-yl]-1H,2H,3H,4H-pyrido[2,3-d]pyrimidine-2,4-dione, by e.g. cyclizing substituted heterocyclic compounds to provide 7-chloro-6-fluoro-1-[4-methyl-2-(propan-2-yl)pyridin-3-yl]-1H,2H,3H,4H-pyrido[2,3-d]pyrimidine-2,4-dione, and resolution
	SEENI S R; SOMISETTI N R; NANDEPU H; NANDEPU V R
	2023-08-28
专利权人	METROCHEM API PVT LTD (METR-Non-standard)
申请日期	2023-08-28
专利号	IN202341057529-A
成果简介	NOVELTY - Preparing (P1) 7-chloro-6-fluoro-1-[4-methyl-2-(propan-2-yl)pyridin-3-yl]-1H,2H,3H,4H-pyrido[2,3-d]pyrimidine-2,4-dione (III): comprises (a) reacting substituted heterocyclic compounds of formula (IV), with 4-methyl-2-(propan-2-yl)pyridin-3-amine (V) in the presence of a coupling agent to provide substituted heterocyclic compounds (VI); (b) cyclizing (VI) in the presence of a suitable base to provide 7-chloro-6-fluoro-1-[4-methyl-2-(propan-2-yl)pyridin-3-yl]-1H,2H,3H,4H-pyrido[2,3-d]pyrimidine-2,4-dione (II); and (c) resolution of (II) in the presence of a suitable resolving agent to provide (III). USE - The process is useful for preparing 7-chloro-6-fluoro-1-[4-methyl-2-(propan-2-yl)pyridin-3-yl]-1H,2H,3H,4H-pyrido[2,3-d]pyrimidine-2,4-dione that is used as a key intermediate for the synthesis of sotorasib. ADVANTAGE - The process is cost effective and commercially viable. DETAILED DESCRIPTION - Preparing (P1) 7-chloro-6-fluoro-1-[4-methyl-2-(propan-2-yl)pyridin-3-yl]-1H,2H,3H,4H-pyrido[2,3-d]pyrimidine-2,4-dione of formula (III): comprises (a) reacting substituted heterocyclic compounds of formula (IV), with 4-methyl-2-(propan-2-yl)pyridin-3-amine of formula (V) in the presence of a coupling agent to provide substituted heterocyclic compounds of formula (VI); (b) cyclizing (VI) in the presence of a suitable base to provide 7-chloro-6-fluoro-1-[4-methyl-2-(propan-2-yl)pyridin-3-yl]-1H,2H,3H,4H-pyrido[2,3-d]pyrimidine-2,4-dione of formula (II); and (c) resolution of (II) in the presence of a suitable resolving agent to provide (III). X = halo. INDEPENDENT CLAIMS are included for: preparing (P2) (III), comprising (a) resolution (II) with di-p-toluoyl-D-tartaric acid to provide 7-chloro-6-fluoro-1-[4-methyl-2-(propan-2-yl)pyridin-3-yl]-1H,2H,3H,4H-pyrido[2,3-d]pyrimidine-2,4-dione-di-p-toluoyl-D-tartaric acid (IIIa), and (b) treating (IIIa) with a suitable base comprises disodium hydrogen phosphate (disodium phosphate) or calcium phosphate or potassium phosphate to provide (III); and preparing (P3) sotorasib, comprising (a) preparing (II) or (III), and (b) converting (II) or (III) into sotorasib.
IPC 分类号	C07D-239/54 ; C07D-471/04 ; C07D-487/04 ; C07D-495/14
国家	印度
专业领域	医药卫生
语种	英语
成果类型	专利
文献类型	科技成果
条目标识符	http://119.78.100.226:8889/handle/3KE4DYBR/20651
专题	中国科学院新疆生态与地理研究所
作者单位	METROCHEM API PVT LTD (METR-Non-standard)
推荐引用方式 GB/T 7714	SEENI S R,SOMISETTI N R,NANDEPU H,et al. Preparing 7-chloro-6-fluoro-1-[4-methyl-2-(propan-2-yl)pyridin-3-yl]-1H,2H,3H,4H-pyrido[2,3-d]pyrimidine-2,4-dione, by e.g. cyclizing substituted heterocyclic compounds to provide 7-chloro-6-fluoro-1-[4-methyl-2-(propan-2-yl)pyridin-3-yl]-1H,2H,3H,4H-pyrido[2,3-d]pyrimidine-2,4-dione, and resolution. IN202341057529-A[P]. 2023.

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