盐酸普拉格雷的合成工艺改进

摘要

以2-氧代-N-三苯甲基-2,4,5,6,7,7a-六氢噻吩并[3,2-c]吡啶为原料,经酰化、脱保护反应制得2-乙酰氧基-5,6,7,7a-四氢噻吩并[3,2-c]吡啶盐酸盐(4); 4与2-溴-2-(2-氟苯基)-1-环丙基乙酮缩合得2-[2-(乙酰氧基)-6,7-二氢噻吩并[3,2-c]吡啶-5(4H)-基]-1-环丙基-2-(2-氟苯基)乙酮(5); 5再经成盐反应得到盐酸普拉格雷,总收率75.0%,其结构经1H NMR和MS(ESI)确证.%2-Acetoxy-5-trityl-4,5,6,7-tetrahydrothieno[3,2-c] pyridine(4) was obtained by acetyla-tion and deprotection from 5-trityl-5,6,7,7a-tetrahydro-4H-thieno[3,2-c] pyridine-2-one.Then 4 was condensed with 2-bromo-1-cyclopropyl-2-(2-fluorophenyl) ethanone to prepare 2-[2-(acetyloxy)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl]-1-cyclopropyl-2-(2-fluorophenyl) ethanone(5).5 was sali-fied to finally give prasugrel hydrochloride, with an overall yield of 75.0%.The structure was con-firmed by 1H NMR and MS(ESI).