第 52 卷第 3 期 Vol. 52 No. 3 2022 年 6 月 Jun 2022

所属栏目：医药及中间体 莫索尼定杂质的合成研究

门 靖，牛国龙，温锦荣，李成利，张 怡 （西安万隆制药股份有限公司，陕西 西安 710119）

摘　要：为有效控制莫索尼定原料药质量、建立质量标准，采用2-甲基-4，6-二氯-5-氨基嘧啶为起始原料，经与N-乙酰基-2-咪唑烷酮缩合，再于不同条件下水解制备了莫索尼定杂质A和杂质B 2个有关物质，并对合成工艺进行了优化。采用1H NMR、13C NMR和MS对其进行结构表征确证。优化条件下，杂质A和杂质B总收率分别为44.8%和45.5%（以2-甲基-4，6-二氯-5-氨基嘧啶计），纯度均高于99.2%（HPLC法）。合成工艺合理可行、反应条件温和，制备的杂质纯度高，可作为莫索尼定药物质量控制的杂质对照品。

关键词：2-甲基-4，6-二氯-5-氨基嘧啶；莫索尼定；杂质A和杂质B

中图分类号：R914　　文献标识码：A　　文章编号：1009-9212（2022）03-0033-04

Synthesis of Related Impurities Existed in Moxonidine

MEN Jing, NIU Guo-long, WEN Jin-rong, LI Cheng-li, ZHANG Yi (Xi’an Wanlong Pharmaceutical Co., Ltd., Xi’an 710119, China）

Abstract：In order to effectively control the quality of Moxonidine and establish the quality standard of moxonidine, 2-methyl-4,6-dichloro-5-aminopyrimidine was used as the starting material, and the intermediate was obtained by condensation reaction with N-acetyl-2-imidazolidinone. Then two related substances of moxonidine included in European Pharmacopoeia were prepared under different hydrolysis conditions: impurity A and impurity B. Their structures were confirmed by 1H NMR, 13C NMR and MS. The conditions for synthetic process were optimized. The total yields of impurity A and impurity B were 44.8% and 45.5% (calculated by 2-methyl-4,6-dichloro-5-aminopyrimidine), respectively, and the purity (HPLC) was higher than 99.2%. This synthetic process is reasonable and feasible, the reaction conditions are mild, and the impurity purity is high. It can be used as the impurity reference substance for the quality control of moxonidine.

Key words：2-methyl-4,6-dichloro-5-aminopyrimidine; Moxonidine; impurity A and B

作者简介：门 靖（1986—），男，陕西临潼人，高级工程师，硕士，研究方向：医药研发、原料药技术转移及活性小分子开发（E-mail: 1257391857@qq.com）。

收稿日期：2022-03-15