4-[1-烷基-5-氧代-1H-1,2,4-三唑-4(5H)-基]-苯甲酸的合成  

Synthesis of 4-[1-alkyl-5-oxo-1H-l,2,4-triazol-4(5H)-yl]benzoic acids

作　　者：陈海[1] 姚建忠[1] 盛春泉[1] 缪震元[1] 张万年[1] 

机构地区：[1]第二军医大学药学院,上海200433

出　　处：《药学实践杂志》2013年第6期442-445,共4页Journal of Pharmaceutical Practice

基　　金：国家自然科学基金(30772674;30930107)

摘　　要：目的制备用于全合成卡泊芬净类环六脂肽抗真菌剂的关键脂肪酸侧链4-[1-烷基-5-氧代-1H-1,2,4-三唑-4(5H)-基]-苯甲酸(5)。方法以对氨基苯甲酸(1)为起始原料,经氨基苯氧羰酰化、肼解、甲脒环合及N-烃化4步反应制备目标化合物。结果以42.9%~46.2%的总收率成功合成了目标化合物5a^5n,其结构经电喷雾质谱(ESI-MS)和氢谱(~1H NMR)确证;所有目标化合物均为首次报道。结论该合成路线具有操作简便及收率高等优点,适合工业化生产。Objective To prepare 4-[ 1-alkyl-5-oxo-1H-1,2,4-triazol-4 （5H） -yl] benzoic acids （5）, which was the key fatty acid chain pharmaceutical intermediates for the total synthesis of novel caspofungin-like eyclohexa lipopeptide antifungal agents. Meth- ods Starting from 4-aminobenzoic acid （ 1 ） , the target compounds 5a - 5n were prepared via amino phenoxy-carbonyl acylation, hydrazinolysis, formamidine cyclization, and the N -alkylation reaction, respectively. Results Target compounds 5a - 5n had been successfully synthesized with the overall yield ranged from 42.9% to 46.2%. Their structures were confirmed by ESI-MS and ^1 H-NMR spectra. All target compounds were reported for the first time. Conclusion The process developed had several advantages such as convenient workup and high yield, which was suitable to industrial production.

关 键 词：4-[1-烷基-5-氧代-1H-1 2 4-三唑-4(5H)-基]-苯甲酸 合成 环六脂肽 卡泊芬净 抗真菌 

分 类 号：R914.5[医药卫生—药物化学]