莫索尼定杂质的合成研究  

Synthesis of Related Impurities Existed in Moxonidine

作　　者：门靖 牛国龙 温锦荣 李成利 张怡 MEN Jing;NIU Guo-long;WEN Jin-rong;LI Cheng-li;ZHANG Yi(Xi'an Wanlong Pharmaceutical Co.,Ltd.,Xi'an 710119,China)

机构地区：[1]西安万隆制药股份有限公司,陕西西安710119

出　　处：《精细化工中间体》2022年第3期33-36,共4页Fine Chemical Intermediates

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B2个有关物质,并对合成工艺进行了优化。采用^(1)H NMR、^(13)C 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。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:impurityA and impurityB.Their structures were confirmed by ^(1)H NMR,^(13)C NMR and MS.The conditions for synthetic process were optimized.The total yields of impurityAand impurityBwere 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.

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 

分 类 号：R914[医药卫生—药物化学]