lesinurad的合成工艺研究  

Synthesis of lesinurad

作　　者：田禾[1,2] 蔡文卿[1,2] 谢亚非[1] 刘钰强 魏鹏[1] 高志刚[1] 汤立达[1] 徐为人[1] 赵桂龙[1] 

机构地区：[1]天津药物研究院有限公司天津市新药设计与发现重点实验室,天津300193 [2]山东大学化学与化工学院,山东济南250100

出　　处：《现代药物与临床》2015年第1期1-7,共7页Drugs & Clinic

基　　金：国家自然科学基金资助项目(21302141);天津市应用基础与前沿技术研究计划项目(14JCQNJC12900)

摘　　要：目的寻找一条合成尿酸转运体1(URAT1)抑制剂lesinurad的实用的合成路线。方法利用1-溴萘和环丙基溴化镁作为起始原料,经过10步反应合成了目标化合物lesinurad,并着重研究了由中间体4-环丙基-1-萘基异硫氰酸酯(4)合成中间体3-氨基-4-(4-环丙基萘-1-基)-1H-1,2,4-三唑-5(4H)-硫酮(7)的方法。结果合成了目标化合物,并利用IR、MS和1H-NMR确证了结构,此路线所得产品收率为18.2%,质量分数为99.17%。同时得到了一条由化合物4合成化合物7的新路线,大幅度提高了合成化合物7的收率。结论得到了一条合成lesinurad的实用路线,并获得了一种产率更高的合成重要中间体7的新方法。Objective To find a practical synthetic route of uric acid transporter 1 （URAT1） inhibitor lesinurad. Methods 1-Bromonaphthalene and cyclopropylmagnesium bromide were used as starting materials. The target compound lesinurad was synthesized by 10 steps. The synthetic route of the intermediate 3-amino-4-（4-cyclopropylnaphthalen- 1-yl）- 1H- 1,2,4-triazole-5（4H）- thione （7） starting from 4-cyclopropylnaphthalen-l-yl isothiocyanate （4） was studied with expectation of improving yield. Results The target compound was synthesized and characterized by IR, MS, and ^1H-NMR. The overall yield of this route was 18.2%, and the purity was 99.17%. A new synthetic route of compound 7 starting from compound 4 was developed with significantly improved yield. Conclusion A practical synthetic route of lesinurad is obtained. A new synthetic route of the key intermediate 7 is developed with significantly improved yield.

关 键 词：lesinurad URAT1抑制剂 合成工艺 高尿酸血症 痛风 

分 类 号：R914[医药卫生—药物化学]