厄达替尼的新合成方法  

New and Convergent Synthesis of Erdafitinib

作　　者：林楠 师帆 茆勇军[2] Lin Nan;Shi Fan;Mao Yongjun(Shanghai Pharmaceutical School,Shanghai 200135,China;Shanghai University of Engineering Science,Shanghai 201620,China.)

机构地区：[1]上海市医药学校,上海200135 [2]上海工程技术大学,上海201620

出　　处：《山东化工》2023年第6期13-15,18,共4页Shandong Chemical Industry

摘　　要：设计并完成厄达替尼(1)新的汇聚式合成工艺路线,优化得到50 g级别的目标产物。采用市场易于购买的原料喹喔啉-2-醇、4-溴-1-甲基-1H-吡唑、2-溴-1,1-二甲氧基乙烷等为起始原料,制备得到关键中间体3,5-二甲氧基苯基异丙基乙烷-1,2-二胺(17),2步反应收率89%,纯度98.8%。化合物17和7-溴-2-(1-甲基-1H-吡唑-4-基)喹喔啉(8)偶联得到厄达替尼,收率为89%,纯度为99.4%,7步反应总收率54%。A new and convergent synthetic route of erdafitinib on a 50 grams-scale has been developed,from the commercially available chemicals quinoxalin-2-ol,4-bromo-1-methyl-1H-pyrazole,and 2-bromo-1,1-dimethoxyethane.The key intermediate 3,5-dimethoxyphenyl-isopropylethane-1,2-diamine(17)was prepared from 2-bromo-1,1-dimethoxyethane in 89%yield over two steps and 98.8%purity.Erdafitinib was obtained from 7-bromo-2-(1-methyl-1H-pyrazol-4-yl)quinoxaline(8)and 17 in 89%yield and 99.4%purity.There are 7 steps in this convergent synthesis route and the overall yield is 54%.

关 键 词：厄达替尼 新路线 合成工艺研究 

分 类 号：TQ460[化学工程—制药化工]