2-取代苯并恶唑衍生物的合成及其在药物合成中的应用  

Synthesis of 2-Substituted Benzoxazole Derivatives and their Application in Pharmaceutical Synthesis

作　　者：王芝元 王合珍 王京 张磊 Wang Zhi-yuan;Wang He-zhen;Wang Jing;Zhang Lei(School of Pharmacy,Zunyi Medical University,Zunyi Guizhou 563000)

机构地区：[1]遵义医科大学药学院,遵义贵州563000

出　　处：《国外医药（抗生素分册）》2024年第1期61-70,共10页World Notes on Antibiotics

基　　金：遵义市科学技术局重点学科(创新团队)建设项目[(2020)293]。

摘　　要：2-取代苯并恶唑是一类重要的杂环骨架,其在药物合成中受到广泛关注与运用。本文以廉价易得的邻氨基苯酚和芳香醛为原料,通过一锅两步法优化第一步与第二步反应条件,确定第一步二氧六环为溶剂,室温空气气氛反应5h;第二步2,3-二氯-5,6-二氰基苯醌为氧化剂,室温空气气氛反应1h,氧化环化合成一系列2-取代苯并恶唑衍生物,同时将该方法运用于药物Tafamidis的合成中。目标化合物结构经^(1)H-NMR、^(13)C-NMR和HRMS确证。该方法条件温和、操作简便、底物普适性广以及具有一定的实用性,为2-取代苯并恶唑化合物合成提供了一种新的思路。2-Substituted benzoxazoles are a kind of important heterocyclic skeleton,which have been widely considered and applied in drug synthesis.In this work,the first and second steps of the reaction were optimized by a one-pot two-step method using inexpensive and readily available o-aminophenol and aromatic aldehyde as raw materials.The first step involved the use of dioxane as a solvent,and the reaction was conducted at room temperature under an air atmosphere for five hours.The second step involved the use of 2,3-dichloro-5,6-dicyanobenzoquinone as an oxidant,and the reaction was carried out at room temperature under an air atmosphere for one hour.This resulted in the synthesis of a number of 2-substituted benzoxazole derivatives through oxidative cyclization.Meanwhile,the approach was applied to the synthesis of the medicine Tafamidis.The structure of the target compound was confirmed by ^(1)H-NMR,^(13)C-NMR,and HRMS.The method has mild conditions,simple and convenient operation,wide substrate universality,and certain practicability,which provides a new idea for the synthesis of the 2-substituted benzoxazole compound.

关 键 词：一锅两步法 合成 2-取代苯并恶唑 他法米迪 工艺 应用 

分 类 号：R978.1[医药卫生—药品]