帕博西尼关键侧链中间体的合成研究  

Synthesis of A Key Side Chain Intermediate of Palbociclib

作　　者：张彬 李新志 孔祥雨 崔新强 杨利 段崇刚 刘文涛 ZHANG Bin;LI Xin-zhi;KONG Xiang-yu;CUI Xin-qiang;YANG Li;DUAN Chong-gang;LIU Wen-tao(Shandong Key Laboratory of Chemical Drugs,Shandong Academy of Pharmaceutical Sciences,Jinan 250104,China)

机构地区：[1]山东省药学科学院山东省化学药物重点实验室,山东济南250101

出　　处：《食品与药品》2022年第6期553-556,共4页Food and Drug

摘　　要：目的 合成帕博西尼关键侧链中间体。方法 以2-氨基吡啶为原料,经溴代、氧化、偶联、还原反应合成了4-(6-氨基吡啶-3-基)-哌嗪-1-羧酸叔丁酯。结果 目标产物总收率56%,纯度99%以上,其结构经熔点,质谱(MS),核磁共振氢谱(^(1)H NMR)确证。结论 该工艺易于操作,避免使用苛刻条件,可提高收率,降低成本,提高生产安全性,易于工业化生产。Objective To synthetize a key side chain intermediate of palbociclib,1-Boc-4-(6-aminopyridin-3-yl)piperazine.Methods 1-Boc-4-(6-aminopyridin-3-yl) piperazine was synthesized through a four-step reaction including bromination,oxidation,coupling and reduction,using 2-aminopyridine as the starting material.Results The total yield was 56 % and the purity was above 99 %.The structure of the target product was confirmed by melting point determination,MS and ^(1)H NMR.Conclusion The improved process can reduce the cost and avoid harsh conditions,increase yield,simplify operation,improve production safety,and is suitable for industrial production.

关 键 词：帕博西尼 侧链 4-(6-氨基吡啶-3-基)-哌嗪-1-羧酸叔丁酯 

分 类 号：R914.5[医药卫生—药物化学]