N-(3,5-二氨基-6-氯吡嗪-2-甲酰基)硫脲的合成新工艺  

New Synthetic Process of 1-( 3,5-Diamino-6-chloropyrazine-2-carbonyl)-thiourea

作　　者：朱剑平 余洛汀[1] 林文清 ZHU Jian-ping;YU Luo-ting;LIN Wen-qing(State Key Laboratory of Biotherapy,Sichuan University,Chengdu 610041,China;Chengdu Porton Pharmaceutical Corporation Ltd.,Chengdu 610000,China)

机构地区：[1]四川大学生物治疗国家重点实验室,四川成都610041 [2]成都博腾药业有限公司,四川成都610000

出　　处：《合成化学》2018年第9期699-702,共4页Chinese Journal of Synthetic Chemistry

摘　　要：本文开发了一种化合物N-(3,5-二氨基-6-氯吡嗪-2-甲酰基)硫脲(TM)的合成新工艺。将叔丁醇钾与硫脲原位反应制得硫脲钾盐,再与3,5-二氨基-6-氯-吡嗪甲酸甲酯发生亲核反应一步合成TM,收率85%,化学纯度99%,其结构经~1H NMR,^(13)C NMR和LC-MS表征。该合成工艺稳定,已放大至公斤级。A new synthetic process of 1-（3,5-diamino-6-chloropyrazine-2-carbonyl）-thiourea（ TM ） was developed. TM in total yield of 85% and purity of 99% was prepared by only one step reaction of methyl 3,5-diamino-6- chloropyrazine-2-carboxylate with thiourea potassium salt which was obtained by in-situ reaction of thiourea with potassium tert-butoxide. The structure was confirmed by 1 H NMR, 13 C NMR and LC-MS. The process is stable and had been enlarged to kilogram scale production.

关 键 词：3 5-二氨基-6-氯-吡嗪甲酸甲酯 N-(3 5-二氨基16-氯吡嗪-2-甲酰基)硫脲 药物合成 工艺 

分 类 号：O626.4[理学—有机化学] O621.3[理学—化学]