摘要
本文以丙二腈为起始原料,经亚硝酸钠亚硝化、硝酸胍环合、Fe/HCl还原后与硫酸成盐得到2,4,5,6-四氨基嘧啶硫酸盐,接着与1,3-二羟基丙酮反应成环、SOCl_(2)氯代后与L-对甲氨基苯甲酰谷氨酸二乙酯缩合,最后水解得到目标产物甲氨蝶呤,总收率21.07%(以丙二腈计),HPLC纯度99.68%。产物结构经^(1)HNMR、^(13)CNMR和以及ESI-MS进行确证。
In this paper,malonitrile was used as starting materials,underwent a salification with sulfuric acid after sodium nitrite nitrosation,guanidine nitrate cyclization,and Fe/HCl reduction to obtain 2,4,5,6-tetraaminopyrimidine sulfate.And then reacted with 1,3-dihydroxyacetone to form a ring,and after chlo-rination with SOCl_(2),it condensed with L-p-methylaminobenzoyl glutamate diethyl ester.Finally,the target product methotrexate was obtained by hydrolysis.The total yield was 21.07%(based on malonitrile),and the purity of HPLC was 99.68%.The structure of the product was confirmed by^(1)HNMR,^(13)CNMR and ESI-MS.
作者
陈文斌
张毅
杨元勇
CHEN Wen-bin;ZHANG Yi;YANG Yuan-yong(Engineering Technology Research Center for Chemical Drug R&D,College of Pharmacy,Guizhou Medical University,Guiyang 550004,China)
出处
《化学研究与应用》
CAS
北大核心
2024年第5期1169-1177,共9页
Chemical Research and Application
基金
中央引导地方科技发展资金项目(黔科中引地[2022]4017)资助
贵州省教育厅服务“四新”“四化”科技攻关项目(黔教技[2022]004号)资助
贵州省科技计划项目(黔科合支撑[2020]4Y208号)资助
贵阳市科技计划项目(筑科合同[2023]48-6号)资助
贵州医科大学高层次人才启动基金项目,(校博合J字[2021]023号)资助。
关键词
甲氨蝶呤
合成工艺
改进研究
methotrexate
synthesis process
improvement research
