抗帕金森病药雷沙吉兰的合成工艺优化  

Optimizing the Synthesis Process of Rasagiline:An Anti-Parkinson's Agent

作　　者：李杰 赖永莉 Li Jie;Lai Yongli(Department of Pharmacy,Sichuan Vocational College of Health and Rehabilitation,Zigong 643000,China)

机构地区：[1]四川卫生康复职业学院药学系,四川自贡643000

出　　处：《山东化工》2021年第10期1-2,7,共3页Shandong Chemical Industry

基　　金：四川卫生康复职业学院校级项目(CWKY-2018Y-02)。

摘　　要：以1-茚酮(1)为原料,在室温下与盐酸羟胺作用制得2,3-二氢-1H-茚-1-酮肟(2)。然后以乙醇作溶剂,经镍铝合金还原制得1-氨基茚满(3),并应用星点设计-响应面法对还原工艺进行了优化。随后再与对甲苯磺酸炔丙酯反应制得N-炔丙基-1-氨基茚满(4)。最后经L-酒石酸拆分、甲磺酸成盐得到雷沙吉兰(5)。以1为原料计算总收率约为31%。Treating1-indanone(1)as original material,which reacted with hydroxylamine hydrochloride in room temperature to afford 2,3-dihydro-1H-indene-1-ketoxime(2).Then,treating ethanol as solvent,compound 2 reacted withNi-Alto give 1-indanamine(3).Thereafter,the process conditions of synthesizing 3were optimized by central composite design-response surface methodology.Then,compound 3 wastreated with propargyl p-toluenesulfonate andhydrochloric acidto afford N-propargyl-1-indanaminehydrochloride(4).Finally,the target product rasagiline(5)was enantioseparated by L-tartaric acid and prepared by reacting with methanesulfonic acid.The overall yield was about 31%(based on 1).

关 键 词：帕金森病 雷沙吉兰 工艺优化 合成 

分 类 号：R914.3[医药卫生—药物化学]