摘要
为有效控制米诺地尔原料药质量标准,本研究以现有工艺为基础设计合成了8个有关杂质:杂质1、杂质2、杂质3、杂质4、杂质5、杂质6、杂质7以及杂质8。以2,4-二氨基-6-氯-嘧啶为起始原料,分别通过N-氧化反应、亲核取代反应、氧化反应得到杂质。通过HPLC、^(1)H NMR和LC-MS等手段表征,分别对其进行结构确证,结果表明:反应条件温和,制备的杂质纯度高,可作为米诺地尔原料药质量控制的杂质对照品。
In order to effectively control the quality standard of minoxidil,eight related impurities were designed and synthesized based on the existing process:impurity 1,impurity 2,impurity 3,impurity 4,impurity 5,impurity 6,impurity 7 and impurity 8.Using 2,4-diamino-6-chloro-pyrimidine as the starting material,impurities were obtained by N-oxidation reaction,nucleophilic substitution reaction and oxidation reaction,respectively.The structure was confirmed by HPLC,^(1)H NMR and LC-MS.The results showed that the reaction conditions were mild and the purity of the prepared impurities was high,which could be used as the impurity reference substance for the quality control of minoxidil.
作者
李鸣海
陆琴亚
闫煜
陈敖
陈正军
LI Minghai;LU Qinya;YAN Yu;CHEN Ao;CHEN Zhengjun(Shanghai Pharma Group(Changzhou)Kony Pharmaceutical Co.,Ltd.,Changzhou 213105 China)
出处
《山东化工》
2025年第2期71-73,78,共4页
Shandong Chemical Industry
关键词
米诺地尔
N-氧化反应
杂质
亲核取代
合成
minoxidil
N-oxidation reaction
impurity
nucleophilic substitution
synthesis
