正交法优选1-氨甲基-1,2,3,4-四氢异喹啉盐酸盐的合成工艺条件  

Optimization of synthetic technological conditions for 1-aminomethyl1,2,3,4-tetrahydroisoquinoline hydrochloride with orthogonal design

作　　者：张昕宇[1] 程训官[1] 郑小红[1] 王宇[1] 彭杨[1] 余瑜[1] 

机构地区：[1]重庆医科大学药学院药物化学与生物材料研究室、重庆高校药物工程研究中心,重庆400016

出　　处：《重庆医科大学学报》2012年第3期224-228,共5页Journal of Chongqing Medical University

基　　金：科技部重大专项资助项目(编号:2010ZX09401-306-1-1);国家自然科学基金资助项目(编号:30772595、30171070、30371632);重庆市科委攻关资助项目(编号:20021425);重庆市教委资助项目(编号:20021804)

摘　　要：目的:利用正交实验法优选药物重要中间体1-氨甲基-1,2,3,4-四氢异喹啉盐酸盐(1)的合成工艺条件。方法:采用正交实验方法,考察合成(1)中的酰化、邻苯二甲酰亚胺N-烃化、Bischler-Napieralski反应、肼解与还原等主要反应的关键条件对收率的影响,筛选出主要反应的优选实验条件。结果:合成(1)的总收率达到了62.4%,约为原来总收率的2.5倍。结论:该合成工艺路线具有原料廉价易得、反应操作简便、兼顾环保以及产品收率高且品质好等优点;具有较好的工业化生产前景。Objective：To optimize the synthetic technological conditions of 1-aminomethyl-1,2,3,4-tetrahydroisoquinoline hydrochloride as important intermediate for drugs by orthogonal experimental method.Methods：The target product was synthesized from β-phenethylamine by phthalimide N-hydrocarbylation reaction,Bischler-Napieralski reaction,cyclization with Bischler-Napieralski method,hydrazinolysis reaction,reduction and salification.The key factors on each reaction were discussed separately and optimized by orthogonal experiment.Results：The overall yield was 65%,2.5 times as much as that of the reported.Conclusion： The optimized synthetic route has promise in industrial production for its cheap and readily available raw materials,easy and environmentally-friend processes,high yield and good quality of products.

关 键 词：1-氨甲基-1 2 3 4-四氢异喹啉 合成 正交实验 工艺条件 中间体 

分 类 号：R914.5[医药卫生—药物化学]