盐酸普拉格雷合成工艺的改进

Optimization of synthetic process of prasugrel hydrochloride

目的改进盐酸普拉格雷的合成工艺,以便于放大生产,提高产品纯度。方法以邻氟苯乙酸和环丙烷甲酸甲酯为原料合成环丙基-2-氟苄基酮,再用NBS溴代得到α-环丙基羰基-2-氟苄基溴,在碱存在下,与2-氧代.2,4,5,6,7,7a-六氢噻吩并[3,2-c]吡啶盐酸盐发生亲核取代反应,再经乙酰化和成盐反应制得盐酸普拉格雷。结果优化后的合成工艺操作简便,成本低廉,可获得高纯度的盐酸普拉格雷。结论新工艺总产率达到48%,有利于工业生产。

Objective To improve the synthetic process of prasugrel hydrochloride in order to enlarge production and get high purity. Methods 2-fluorine phenylacetic acid was reacted with methyl eyclopropanccarboxylate, followed by bromination with NBS to afford α-cyclopropyl carbonyl-2-fluorobenzyl bromide. The latter was condensed with 2-oxo-2,4,5,6,7,7a-hexahydro-thieno [ 3,2-c ] pyridine hydrochloride,and then acetylated and solified to finally afford prasugrel hydrochloride. Results The cost of this optimized synthetic process of prasugrel hydrochloride was obviously low,with easy operation process and availability of high purity. Conclusion The overall yield of new process was 48% , which ensured a more appropriate process for industrial production.