通过改良分子内Buchwald-Hartwig交叉偶联反应构建氮杂融合环体系  

Constructing Aza-hetereocycle-fused Ring System Via a Modified IntramolecularBuchwald-Hartwig Cross-coupling Reaction

作　　者：朱辰 高安慧 刘晓玲[1] 白海云 ZHU Chen;GAO Anhui;LIU Xiaoling;BAI Haiyun(Wuya College of Innovation,Shenyang Pharmaceutical University,Shenyang 110016,China;Drug Research Institute of Yangtze Delta,Nantong 226133,China;Biopolar Hongye(Nantong)Pharmaceutical Co.,Ltd.,Nantong 226133,China)

机构地区：[1]沈阳药科大学无涯创新学院,辽宁沈阳110016 [2]长三角药物高等研究院,江苏南通226133 [3]南通弘烨医药科技有限公司,江苏南通226133

出　　处：《山东化工》2025年第7期26-29,32,共5页Shandong Chemical Industry

摘　　要：该研究采用一种改良后的Buchwald-Hartwig偶联反应方法,旨在解决当前合成苯并氮杂卓类并环结构产率低的问题。研究对象主要是苯并氮杂卓类分子,其在生物医学领域具有特殊的生物活性,常用于靶向酶、离子通道和G蛋白偶联受体。通过优化反应条件,确定了以Pd_(2)(dba)_(3)为钯催化剂,Xantphos为配体,DIEA为碱,DMSO为溶剂的合成方法,改善了先前报道的合成方法收率低的缺点,显著提高了反应的收率,达到78.9%。这一反应条件为后续高收率合成含有类似相关结构的重要药物中间体提供了基础。此外,该方法也适用于合成相同结构的六元环,这证明了其在多样化合成中的广泛适用性。这一研究成果不仅为提高产率提供了新思路,还助力于苯并氮杂卓类分子在制药领域的应用与开发,具有重要的科学价值和实际应用意义,为后续研究和开发相关药物中间体奠定了基础。This article aims to address the current problem of low yields in the synthesis of benzazepine-conjugated structures,for which the researchers used a modified Buchwald-Hartwig coupling reaction method.The research was focused on benzazepine molecules,which have specific biological activities in the biomedical field and are commonly used to target enzymes,ion channels,and G-protein coupled receptors.The researchers explored a synthetic method using Pd_(2)(dba)_(3) as a palladium catalyst,Xantphos as a ligand,DIEA as a base,and DMSO as a solvent,which improves the shortcomings of the traditional synthetic method and thus significantly increases the yield of the reaction.By optimizing the reaction conditions and synthesizing a seven-membered ring,the researchers finally achieved an efficient synthesis of benzazepine molecules in 78.9%yield.The successful validation of this reaction condition provides a basis for the subsequent synthesis of important pharmaceutical intermediates containing related structures.In addition,the method is also applicable to the synthesis of six-membered rings of the same structure,which proves its broad applicability in diverse syntheses.This research result not only provides a new idea to improve the yield,but also helps the application and development of benzazepine molecules in the pharmaceutical field,which has important scientific value and practical application significance,and lays the foundation for the subsequent research and development of related drug intermediates.

关 键 词：Buchwald-Hartwig偶联反应 氮杂融合环 苯并氮杂卓 

分 类 号：TQ463[化学工程—制药化工] R914[医药卫生—药物化学]