利鲁唑合成工艺优化  

Improved Synthesis of Riluzole

作　　者：毛远湖 王丽丽 齐双双 张丽 张吉泉 汤磊 Mao Yuanhu;Wang Lili;Qi Shuangshuang;Zhang Li;Zhang Jiquan;Tang Lei(School of Pharmacy,Guizhou Medical University,Guiyang 550004;School of Medicine and Health Management,Guizhou Medical University,Guiyang 550004;Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D,Guiyang 550004,China)

机构地区：[1]贵州医科大学药学院,贵州贵阳550004 [2]贵州医科大学医药卫生管理学院,贵州贵阳550004 [3]贵州省化学合成药物研发利用工程技术研究中心,贵州贵阳550004

出　　处：《广东化工》2020年第5期18-19,37,共3页Guangdong Chemical Industry

基　　金：贵州医科大学化学药仿创技术应用国家地方联合工程技术研究中心(无编号);贵州省高层次创新型人才支持计划(黔科合人才(2016)4015);贵州省研究生教育创新计划项目(黔教合YJSCXJH(2018)019);贵州省科技支撑计划项目(黔科合[2016]支撑2819);贵州省卫生健康委科技基金(gzwjkj2019-1-179);贵阳市科技基金(筑科合[2017]30-28号);贵州省大学生创新计划项目(2018520343,20195200137,2018520355,20195200128)。

摘　　要：以4-三氟甲氧基苯胺和硫氰酸铵为原料,经缩合反应得N-[4-(三氟甲氧基)苯基]-硫脲(4),随后在二氧化锰催化下,经H_2SO_4/NaBr作用环合得到2-氨基-6-三氟甲氧基苯并噻唑(1,利鲁唑),总收率为85.3%,终产物纯度大于99%。中间体及终产物结构经~1H NMR、^(13)C NMR、HRMS确证。此外,通过单因素考察,获得了合成利鲁唑的最佳工艺条件。Starting from 4-(trifluoromethoxy)aniline and ammonium thiocyanate, 1-(4-(trifluoromethoxy)phenyl) thiourea (4) was synthesized via condensation, which was subjected to cyclization under H2SO4/NaBr using MnO2 as the catalyst, and the title compound riluzole (1) was obtained in total yield of 85.3 % and a purity of more than 99 %. The structures of intermediate 4 and target compound 1 were characterized by 1HNMR and 13CNMR. Besides, the optimal preparation conditions were obtained via the investigation of single factor.

关 键 词：利鲁唑 肌萎缩性脊髓侧索硬化症(ALS) 苯并噻唑 工艺优化 

分 类 号：R914.5[医药卫生—药物化学]