摘要
N-乙氧羰基-4-哌啶酮经Vilsmerier氯化甲酰化反应、在碳酸钾作用下与巯基乙酸乙酯环合制得6,7-二氢-4H-噻吩并[3,2-c]吡啶-2,5-二羧酸二乙酯(4),再经肼解、叠氮化、重排及脱保护反应制得2-氨基-6,7-二氢-4H-噻吩并[3,2-c]吡啶-5-羧酸乙酯盐酸盐(8),8经重氮化、水解后再由氢氧化钾碱解、成盐,制得普拉格雷的关键中间体2-氧代-5,6,7,7a-四氢噻吩并[3,2-c]吡啶,总收率约25%。
2-Oxo-5,6,7,7a-tetrahydrothieno [3,2-c]pyridine, the key intermediate of prasugrel, was synthesized from ethyl 4-oxopiperidine-l-carboxylate by Vilsmerier reaction and cyclization with ethyl mercaptoacetate in the presence of K2CO3 to give diethyl 6,7-dihydro-4H-thieno [3,2-c] pyridine-2,5-dicarboxylate （4）, which was subjected to hydrazinolysis, azidation, rearrangement and deprotection to afford ethyl 2-amino-6,7-dihydro-4H-thieno [3,2-c] pyridine- 5-carboxylate hydrochloride （8）, followed by diazotization, hydrolysis, alkaline hydrolysis and salt formation with an overall yield of about 25 %.
出处
《中国医药工业杂志》
CAS
CSCD
北大核心
2013年第1期13-16,共4页
Chinese Journal of Pharmaceuticals
