卢非酰胺的合成工艺改进研究  

Research on the Improvement of Synthesis Process of Lufenamide

作　　者：王清河 刘益平 徐凯浡 钟巧 孔杜林 Wang Qinghe;Liu Yiping;Xu Kaibo;Zhong Qiao;Kong Dulin(Wante Pharmaceutical(Hainan)Co.,Ltd.,Haikou Hainan 570100,China;Hainan Medical College,Haikou Hainan 570100,China)

机构地区：[1]万特制药(海南)有限公司,海南海口570100 [2]海南医学院,海南海口570100

出　　处：《山西化工》2024年第10期8-9,13,共3页Shanxi Chemical Industry

基　　金：海南省重点研发计划项目(ZDYF2024SHFZ065)。

摘　　要：本文对抗癫痫药物卢非酰胺合成工艺进行了改进。以叠氮磷酸二苯酯(DPPA)作为叠氮化试剂,与2,6-二氟苄溴反应得到1-叠氮甲基-2,6-二氟苯,再与丙炔酸甲酯Click环合反应得1-[(2,6-二氟苯基)甲基]-1H-1,2,3-三唑-4-甲酸甲酯,最后氨解得到抗癫痫药物卢非酰胺,总收率约63%。本文发展的方法避免了叠氮化钠的直接使用,以水作为反应媒介,具有良好的工业应用前景。This article improves the synthesis process of the antiepileptic drug Lufenamide.Using DPPA as a diazotizing reagent,it reacted with 2,6-difluorobenzyl bromide to obtain 1-azidomethyl-2,6-difluorobenzene,which was then click cyclized with methyl propargonate to obtain 1-[(2,6-difluorophenyl)methyl]-1H-1,2,3-triazole-4-carboxylic acid methyl ester.Finally,the antiepileptic drug Lufenamide was obtained by ammonolysis,with a total yield of about 63%.The method developed in this article avoids the direct use of sodium azide and uses water as the reaction medium,which has good industrial application prospects.

关 键 词：卢非酰胺 叠氮化 抗癫痫药物 合成工艺 

分 类 号：R944.4[医药卫生—药剂学]