盐酸鲁拉西酮的合成工艺改进  

Improved Synthetic Process of Lurasidone Hydrochloride

作　　者：陈文华[1] 祁秀秀[1] 郭亚楠[1] 

机构地区：[1]常州工程职业技术学院制药与生物工程技术系,江苏常州213164

出　　处：《中国医药工业杂志》2017年第2期157-159,共3页Chinese Journal of Pharmaceuticals

摘　　要：3-(1-哌嗪基)-1,2-苯并异噻唑与(1R,2R)-1,2-双(甲磺酰基氧基甲基)环己烷在甲苯为溶剂、碳酸钾为碱、聚乙二醇400为相转移催化剂条件下反应得4'-(1,2-苯并异噻唑-3-基)-(3a R,7a R)-八氢螺-(2H-异吲哚-2,1'-哌嗪)甲磺酸盐,不经分离直接与顺-5-降冰片烷-外-2,3-二甲酰亚胺在碳酸钾为碱条件下反应制得鲁拉西酮,再在异丙醇中与盐酸成盐得盐酸鲁拉西酮,总收率达83%。该法收率高、操作简便,易于工业化生产。3- （1-Piperazinyl） -1,2-benzisothiazole reacted with （1R,2R） -bis （methanesultonyloxymemyi） - cyclohexane with toluene as solvent, K2CO3 as alkali, polyethylene glycol 400 as phase transfer catalyst to give 4＇- （1,2-benzisothiazol- 3-yl） - （3 aR,7aR） -octahydrospiro [2H-isoindole-2, l＇-piperazinium] methanesulfonate, the latter reacted with bicycle [2.2.1 ] heptane-2-exo-3-exo-dicarboximide to afford lurasidone, then it was formed with hydrochloride to provide the target compound with an overall yield of 83 %. This method had some advantages of simple, easily controlled and high yield for the industrial production.

关 键 词：盐酸鲁拉西酮 合成 (1R 强)-1 2-双(甲磺酰基氧基甲基)环己烷 3-(1-哌嗪基)-1 2-苯并异噻唑 

分 类 号：R971.4[医药卫生—药品]