摘要
为有效控制阿加曲班原料药质量并建立质量标准,以4-碘苯胺为起始原料,经与甲基丙烯醛环合、与苄硫醇偶联、氧化、水解制备阿加曲班杂质3-甲基喹啉-6-磺酸,并优化了合成工艺。优化条件下,杂质纯度99.1%(HPLC),总收率49.5%,其结构经^(1)H NMR、^(13)C NMR和HRMS表征确证。合成工艺原料易得,反应条件温和,制备的杂质纯度高,可作为阿加曲班药物质量控制的杂质对照品。
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^(1)H NMR,^(13)C 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.
作者
胡中元
唐旭静
邢磊
张晓玲
刘彦龙
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)
出处
《精细化工中间体》
CAS
2023年第3期38-40,共3页
Fine Chemical Intermediates
