一种改进的Cham-Evans-Lam偶联反应在1-环丙基-4-碘-1H吡唑制备中的应用  

Application of an Improved Cham-Evans-Lam Coupling Reaction in the Preparation of 1-cyclopropyl-4-iodo-1H pyrazole

作　　者：吕志卿 陈伟荣 张鑫龙 Lv Zhiqing;Chen Weirong;Zhang Xinlong(Zhejiang Hisun Pharmaceutical Co.,Ltd.,Zhejiang Taizhou 318000)

机构地区：[1]浙江海正药业股份有限公司,浙江台州318000

出　　处：《化工时刊》2021年第10期18-21,共4页Chemical Industry Times

摘　　要：Chan-Evans-Lam偶联反应在20世纪90年代被发现以来,经历了快速的发展。作为一种高效的构建碳-碳或碳-杂键的方法,目前已广泛地应用于各种底物中。本文提出了一种改进的Cham-Evans-Lam偶联反应在制备化工中间体1-环丙基-4-碘-1H吡唑中的应用,作为磷脂酰肌醇3-激酶抑制剂类药物的关键原料,1-环丙基-4-碘-1H吡唑的工业化生产的实现对此药研究具有重大意义,原合成方法反应条件苛刻,需在高温,持续通氧的条件下进行,工艺可重复性差,收率低,难以放大生产,并且存在着重大的安全风险。经改进后的方法反应条件温和,操作简便、安全,能够大量制备,产物收率能提高近20%,纯度可以达到98%以上。Chan-Evans-Lam coupling reaction has experienced rapid development since its discovery in the 1990s.It has been extensively utilized in various substrates as an efficient method for carbon-carbon or carbon-heteroatom bondsformation.This paper presents an improved Cham-Evans-Lam coupling reaction in the preparation of chemical intermediate 1-cyclopropyl-4-iodo-1H pyrazole,As a key raw material for phosphatidylin-ositol-3-kinase inhibitor,The realization of industrial productions is of great significance to the research of the drug.The condition of original synthesis method is harsh,it needs to be carried out under high temperature,and continuous oxygen flow.Owing to its low process repeatability and yield,it is difficult to scale up production,and there exists safety risks.The condition of the improved method is very mild,it's easy and safe to operate in large quantities,the yield of the product can be increased by nearly 20%,the purity of which can reach 98%above.

关 键 词：Chan-Evans-Lam偶联反应 1-环丙基-4-碘-1H吡唑 磷脂酰肌醇3-激酶抑制剂 合成 

分 类 号：TQ46[化学工程—制药化工]