文献类型：期刊文献

中文题名：酒石酸唑吡坦的绿色合成工艺研究

英文题名：Improved synthesis of zolpidem tartrate

作者：廖凡[1];关禹[1];黄文武[2];李春刚[2];施小新[1];赵建宏[1]

机构：[1]华东理工大学药学院绿色制药工艺与技术实验室,上海200237;[2]上海现代制药股份有限公司,上海200137

年份：2018

卷号：28

期号：1

起止页码：39

中文期刊名：中国药物化学杂志

外文期刊名：Chinese Journal of Medicinal Chemistry

收录：CSTPCD;;北大核心:【北大核心2017】；CSCD:【CSCD_E2017_2018】；

语种：中文

中文关键词：酒石酸唑吡坦;镇静催眠;工艺改进

外文关键词：zolpidem tartrate ; insomnia; process improvement

摘要：目的优化催眠药酒石酸唑吡坦的生产工艺。方法以6-甲基-2-(4-甲基苯基)咪唑[1,2-a]吡啶(2)为原料,经草酰氯酰化、甲醇酯化后得到中间体2-(6-甲基-2-(4-甲基苯基)咪唑[1,2-a]吡啶)-2-氧代乙酸甲酯,经过Wolff-Kishner-黄鸣龙还原得到6-甲基-2-(4-甲基苯基)咪唑并[1,2-a]吡啶-3-乙酸(唑吡坦酸),唑吡坦酸与二甲胺缩合酰化得到N,N,6-三甲基-2-(4-甲基苯基)咪唑并[1,2-a]吡啶-3-乙酰胺(唑吡坦),最后与L-(+)-酒石酸成盐得到酒石酸唑吡坦。结果与结论优化后的工艺路线比原生产工艺缩短3步反应,总收率为39.0%(以2为原料计),产物纯度高达99.5%。酒石酸唑吡坦的结构经MS、~1H-NMR谱确证,改进后的工艺合成路线原料价廉、易得、低毒,反应条件温和,后处理简单,成本低。
Zolpidem tartrate, a GABA inhibitor, is used for the treatment of insomnia. An improved synthetic process of zolpidem has been developed in this paper. Zolpidem tartrate was synthesized from 6-methyl-2- （p-tolyl） imidazo[ 1,2-aj-pyridine via oxalylation and esterification,then subjected to HUANG Ming Long reduction, followed by condensation with dimethylamine and salt formation, the total yield of zolpidem tartrate was 39.0% （based on 6-methyl-2-（p-tolyl） imidazo E 1,2-a 1-pyridine ）. The HPLC purity of the final product is 99. 5%. The improved process has many advantages compared with those reported procedures, such as inexpensive materials, low cost, milder reaction conditions, higher yield, for which it＇s more suitable for industrial production.