2-5-(3-羟基苯甲酰氨基)-1,3,4-噻二唑基乙酸乙酯的合成

摘要

Synthesis of Ethyl 2-[5-(3-Hydroxybenzamido)-1,3,4-thiadiazol-2-yl]acetateZHU Fei, LI Xin, CHEN Yu-hang, CHEN Huan, WANG Wu, WAN Chun-mei, GAN Zong-jie, YU Yu*College of Pharmaceutical Sciences, Chongqing Medical University, Chongqing 400016, ChinaEthyl 2-[5-(3-hydroxybenzamido)-1,3,4-thiadiazol-2-yl]acetate(1), with total yield of 37.2%, was synthesized by the reactions of saponification, acidification, chlorination, cyclization and amidation from diethyl malonate.The structure was confirmed by 1H NMR, 13C NMR, IR and LC-MS(ESI).The amidation conditions were optimized by orthogonal experiment[L9(34)].The results showed that under the optimum conditions{n[ethyl-(5-amino-1,3,4-thiadiazol-2-yl)acetate] ∶n(NEt3) ∶n(3-hydroxybenzoyl chloride)=1 ∶2 ∶3, reaction at 20 ℃ for 8 h}, the yield of 1 was 75.5%.%以丙二酸二乙酯为起始原料,经选择性皂化、酸化、氯化、环合和酰胺化反应合成了2-[5-(3-羟基苯甲酰氨基)-1,3,4-噻二唑]基乙酸乙酯(1),总收率37.2%,其结构经1H NMR, 13C NMR, IR和LC-MS(ESI)确证.采用正交实验法[L9(34)]优化了酰胺化反应的条件.结果表明:在最优反应条件{n[2-(5-氨基-[1,3,4]-噻二唑)基乙酸乙酯] ∶n(三乙胺) ∶n(间羟基苯甲酰氯)=1 ∶2 ∶3,于20 ℃反应8 h}下,1收率75.5%.