4-环丙基-1,2,5-噁二唑-3-甲酸的连续化合成研究  

Continuous Synthesis of 4-Cyclopropyl-1,2,5-Oxadiazole-3-Carboxylic Acid

作　　者：董艳梅 王一帆 韩孜研 杨宇琨 张睿 

机构地区：[1]江南大学生命科学与健康工程学院,江苏 无锡

出　　处：《药物化学》2023年第3期133-138,共6页Hans Journal of Medicinal Chemistry

摘　　要：4-取代-1,2,5-噁二唑-3-甲酸作为重要的合成模块,在药物化学领域具有着重要价值。现有合成方法存在使用氧化剂(高锰酸钾、硝酸钠),容易产生爆炸隐患,反应难以控制,总收率低等问题。本文介绍了以3-环丙基-3-氧代-丙酸乙酯为原料,经一步反应制备3-环丙基异恶唑-5(4H)酮中间体,并以3-环丙基异恶唑-5(4H)酮为原料制备4-环丙基-1,2,5-噁二唑-3-甲酸的连续化合成方法,对部分关键连续化合成条件进行探究,确定R1反应模块最适停留时间为30 min,氢氧化钠溶液的通入流速为48 μL/min,R2反应模块最适温度为50℃,收率为45%。4-cyclopropyl-1,2,5-oxadiazole-3-carboxylic acid as the bioelectronic row of amide bond has important application value in the field of pharmaceutical chemistry, but the existing conventional synthesis methods use oxidants (potassium permanganate, sodium nitrate), easy to produce explosion risks, difficult to control the reaction, low total yield. In this paper, 3-cyclopropyl isooxazol-5(4H) ketone intermediate was prepared with 3-cyclopropyl isooxazol-5(4H) ketone as raw material, and 4-cyclopropyl isooxazol-1,2,5-oxadiazol-3-carboxylic acid was prepared with 3-cyclopropyl isooxazol-5(4H) ketone as raw material. The optimal residence time of R1 reaction module is 30min, the flow rate of sodium hydroxide solution is 48μL/min, the optimal temperature of R2 reaction module is 50˚C, and the yield is 45%.

关 键 词：4-环丙基-1 2 5-噁二唑-3-羧酸 连续化合成 IL-17抑制剂 

分 类 号：TQ2[化学工程—有机化工]