他泽司他的合成新方法  

A new synthetic method of tazemetostat

作　　者：夏明涛 于玲 李帅 苗光新[1] XIA Mingtao;YU Ling;LI Shuai;MIAO Guangxin(Institute of Traditional Chinese Medicine,Chengde Medical University,Chengde Hebei 067000)

机构地区：[1]承德医学院中药研究所,河北承德067000

出　　处：《天津化工》2025年第2期68-71,共4页Tianjin Chemical Industry

摘　　要：目的:探索他泽司他的新合成方法。方法:选取3-氨基-5-溴-2-甲基苯甲酸甲酯为起始原料,经过两次还原胺化法、胺酯交换及Suzuki偶联反应共4步反应得到目标产物他泽司他。结果:借助高分辨质谱(HRMS)、氢核磁共振(1H-NMR)和碳核磁共振(13C-NMR)等先进的分析技术,对他泽司他及合成过程中的各中间体结构进行了严谨的确证。结论:新合成路线减少了反应步骤,摒弃了萃取和柱层析等后处理方式;反应操作简单、降低了工艺难度和成本,路线总收率高达50.75%,对他泽司他的工业化规模生产提供了一定的参考价值。Tazemetostat is indicated as an EZH2 inhibitor for the treatment of surgically resected metastatic or advanced epithelioid sarcoma and mutant or refractory follicular lymphoma.In this paper,a new synthesis route is established on the basis of the literature.Tazemetostat was synthesized from 3-amino-5-bromo-2-methylbenzoate by four steps of reduction amination,aminoesterification and Suzuki coupling.The total yield was 50.75%.The structures of tazemetostat and its in-termediates were confirmed by HRMS,1H-NMR and 13 C-NMR spectra.The new synthesis route reduces the reaction steps,eliminates the need for extraction and column chromatography steps,and the reaction operation is simple and the cost is lower,which is suitable for industrial production.

关 键 词：他泽司他 EZH2抑制剂 SUZUKI偶联反应 合成工艺 

分 类 号：TQ031.2[化学工程]