| 第 53 卷第 3 期 |  | Vol. 53 No. 3 | | 2023 年 6 月 | Jun 2023 |
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所屬欄目：醫藥及中間體
阿加曲班雜質(zhì)的合成 |
| 胡中元，唐旭靜，邢 磊，張曉玲，劉彥龍*
（正大天晴藥業(yè)集團股份有限公司研究院，江蘇 南京 210000） |
| 摘 要：為有效控制阿加曲班原料藥質(zhì)量并建立質(zhì)量標準，以4-碘苯胺為起始原料，經(jīng)與甲基丙烯醛環(huán)合、與芐硫醇偶聯(lián)、氧化、水解制備阿加曲班雜質(zhì)3-甲基喹啉-6-磺酸，并優(yōu)化了合成工藝。優(yōu)化條件下，雜質(zhì)純度99.1%（HPLC），總收率49.5%，其結構經(jīng)1H NMR、13C NMR和HRMS表征確證。合成工藝原料易得，反應條件溫和，制備的雜質(zhì)純度高，可作為阿加曲班藥物質(zhì)量控制的雜質(zhì)對照品。 |
| 關(guān)鍵詞：阿加曲班；4-碘苯胺；雜質(zhì) |
| 中圖分類(lèi)號：R914 文獻標識碼：A 文章編號：1009-9212（2023）03-0038-03 |
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| Synthesis of Impurity in Argatroban |
| HU Zhong-yuan, TANG Xu-jing, XING Lei, ZHANG Xiao-ling, LIU Yan-long*
(Research Institute of Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Nanjing 210000, China) |
| Abstract：In order to effectively control the quality of Argatroban and establish the quality standard, 4-iodoaniline was used as the starting material, and the intermediate was obtained by cyclization with methacrolein. Argatroban impurity 3-methylquinoline-6-sulfonic acid was synthesized from the intermediate via cross-coupling with benzyl mercaptan, oxidation, hydrolysis, and purification with a purity of 99.1% (HPLC) and an overall yield about 49.5%. The conditions for the synthetic process were optimized. Their structures were confirmed by 1H NMR, 13C NMR and HRMS. This synthetic process is reasonable and feasible, the reaction conditions are mild, and the purity of the impurity is high. It can be used as the impurity reference substance for the quality control of Argatroban. |
| Key words：Argatroban; 4-iodoaniline; impurity |
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作者簡(jiǎn)介：胡中元（1986—），男，安徽蚌埠人，工程師，碩士，研究方向：藥物合成工藝（E-mail：164313963@qq.com）。
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聯(lián) 系 人：劉彥龍，高級工程師，研究方向：藥物合成工藝。
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收稿日期：2023-02-24
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