期刊论文

中文

国际药学研究杂志

1674-0440

2015

42

2

220-224

10.13220/j.cnki.jipr.2015.02.018

本校为第一机构

目的:设计并探索一条工艺稳定、收率较高的抗病毒化合物法匹拉韦(T-705)的合成工艺路线。方法以氨基丙二酸二乙酯盐酸盐为起始原料,氨水氨解后与乙二醛环合得到3-羟基-2-吡嗪酰胺、经硝酸钾硝化后制得3-羟基-6-硝基-2-吡嗪酰胺,再经三氯氧磷氯代、氟化钾氟代制得3,6-二氟-2-氰基吡嗪,水解成盐,最后经过氧化氢(双氧水)氧化制得目标化合物法匹拉韦。结果设计出的合成路线能有效制备目标化合物。结论该合成路线各步反应中除氟取代需要严格去水外,其余各步反应条件较温和且操作简单、收率稳定,适合规模制备。

Objective: To design and investigate an effective synthetic route of the antivirus compound favipiravir (T-705) with a stable and high yield. Methods: The commercial available diethyl aminomalonate hydrochloride was selected as the starting material. The product of aminolysis was cyclized with glyoxal to yield 3-hydroxy-2-pyraziamide, which was subjected to nitration with KNO3, chlorination and dehydration with POCl3 and fluorination with KF to afford 3, 6-difluoropyrazin-2-carbonnitrile. The difluorate product was further hydrolyzed and oxidiz...