(5-氨基-[1,3,4]噻二唑-2-基)-丙酸乙酯的合成工艺改进  

Process Improvement on the Synthesis of(5-Amino-[1,3,4]thiadiazol-2-yl)-propionic Acid Ethyl Ester

作　　者：陈世强[1] 朱飞[1] 李鑫[1] 陈宇航[1] 陈向[1] 余瑜[1] 

机构地区：[1]重庆医科大学药学院,重庆400016

出　　处：《合成化学》2016年第7期647-649,共3页Chinese Journal of Synthetic Chemistry

基　　金：国家自然科学基金资助项目(81172097;30371632)

摘　　要：以丁二酸酐为起始原料,经醇解和酰化反应制得丁二酸单乙酯酰氯（3）;3经甲烷磺酸催化与氨基硫脲环合合成了重要药物中间体——（5-氨基-[1,3,4]噻二唑-2-基）-丙酸乙酯,其结构经-1H NMR,IR和MS确证。运用正交试验对环合反应条件进行优化。最优反应条件为：3 132 mmol,n（氨基硫脲）∶n（3）∶n（甲烷磺酸）=1∶3∶3,于110℃反应3 h,总收率51.3%。Succinic acid monoethyl ester chloride （3） was prepared by alcoholysis, acetylation reaction from succinic anhydride. The important intermediate, （ 5-amino- [ 1,3,4 ] thiadiazol-2-yl） -propionic acid ethyl ester, was synthesized by cyclization of 3 with thiosemicarbazide catalyzed by methane sulfo- nic acid. The structure was confirmed by 1H NMR, IR and MS. The reaction conditions for cyclizating reaction was investigated by the orthogonal design. The results showed that the optimal reaction condi- tions were as followed： 3 132 mmol, n（thiosemicarbazide） ：n（3） ： n（methane sulfonic acid） = 1：3：3, reaction at 110 ℃ for 3 h, the total yield was 51.3%.

关 键 词：丁二酸酐 1 3 4-噻二唑 丙酸乙酯 环合 药物合成 工艺改进 

分 类 号：O621.3[理学—有机化学]