| 第 52 卷第 3 期 |  | Vol. 52 No. 3 | | 2022 年 6 月 | Jun 2022 |
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所屬欄目：醫藥及中間體
莫索尼定雜質(zhì)的合成研究 |
| 門(mén) 靖，牛國龍，溫錦榮，李成利，張 怡
（西安萬(wàn)隆制藥股份有限公司，陜西 西安 710119） |
| 摘 要：為有效控制莫索尼定原料藥質(zhì)量、建立質(zhì)量標準，采用2-甲基-4，6-二氯-5-氨基嘧啶為起始原料，經(jīng)與N-乙�；�-2-咪唑烷酮縮合，再于不同條件下水解制備了莫索尼定雜質(zhì)A和雜質(zhì)B 2個(gè)有關(guān)物質(zhì)，并對合成工藝進(jìn)行了優(yōu)化。采用1H NMR、13C NMR和MS對其進(jìn)行結構表征確證。優(yōu)化條件下，雜質(zhì)A和雜質(zhì)B總收率分別為44.8%和45.5%（以2-甲基-4，6-二氯-5-氨基嘧啶計），純度均高于99.2%（HPLC法）。合成工藝合理可行、反應條件溫和，制備的雜質(zhì)純度高，可作為莫索尼定藥物質(zhì)量控制的雜質(zhì)對照品。 |
| 關(guān)鍵詞：2-甲基-4，6-二氯-5-氨基嘧啶；莫索尼定；雜質(zhì)A和雜質(zhì)B |
| 中圖分類(lèi)號：R914 文獻標識碼：A 文章編號：1009-9212（2022）03-0033-04 |
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| 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 |
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作者簡(jiǎn)介：門(mén) 靖（1986—），男，陜西臨潼人，高級工程師，碩士，研究方向：醫藥研發(fā)、原料藥技術(shù)轉移及活性小分子開(kāi)發(fā)（E-mail: 1257391857@qq.com）。
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收稿日期：2022-03-15
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