抗抑郁药盐酸度洛西汀的合成及其中间体杂质的研究  

Study on the Synthesis of Antidepression Drug Duloxetine Hydrochloride and Its Impurity of Intermediates

作　　者：季程宇 谢童杰 吴佳佳 马良秀 郝之奎[1] 颜剑波 徐峰[1] JI Cheng-yu;XIE Tong-jie;WU Jia-jia;MA Liang-xiu;HAOZhi-kui;YAN Jian-bo;XU Feng(Chemical Pharmaceutical Research Institute,Taizhou Vocational ＆ Technical College,Taizhou 318000,China;Neo-Dankong Pharmaceutical Co.,L td.,Taizhou 318000,China)

机构地区：[1]台州职业技术学院化学制药研究所,浙江台州318000 [2]浙江新东港药业股份有限公司,浙江台州318000

出　　处：《合成化学》2018年第6期450-453,共4页Chinese Journal of Synthetic Chemistry

基　　金：台州市科技计划项目(162gy57);台州市"211"人才工程资助项目

摘　　要：以乙酰噻吩和甲胺盐酸盐为原料,经Mannich缩合、酶法还原和缩合共3步反应合成了抗抑郁药盐酸度洛西汀,总收率50.6%,并对第一步反应中的3个杂质进行了1H NMR,13C NMR和MS(ESI)分析,确证为1,5-二(噻吩-2-基)戊烷二酮,3-乙氧基-1-(噻吩-2-基)-1-丙酮和N,N-二[(噻吩-2-基)丙酮-1-基]甲胺。并对反应机理进行了探讨。Duloxetine hydrochloride,with the total yield 50. 6%,was prepared by a three-step reaction of Mannich condensation,enzymatic reduction and condensation from acetylthiophene and methylamine hydrochloride. Three impurities in the first step was analyzed by1 H NMR,13 C NMR and MS（ ESI）,and their structures were confirmed as 1,5-di（ thiophen-2-yl） pentane-1,5-dione,3-ethoxy-1-（ thiophen-2-yl） propan-1-one and 3,3＇-（ methylazanediyl） bis（ 1-（ thiophen-2-yl） propan-1-one）. The plausible reaction mechanism was discussed as well.

关 键 词：乙酰噻吩 度洛西汀 酶法 杂质 合成 

分 类 号：R914.5[医药卫生—药物化学]