摘要
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 POC13 and fluorination with KF to afford 3, 6-difluoropyrazin-2-carbonnitrile. The difluorate product was further hydrolyzed and oxidized to give favipiravlr. Results The target compound was efficiently prepared by the above synthetic route. Conclusion The reaction conditions are mild except the fluoro-substitution, in which all reagents should be dried completely. The synthetic procedure is simple, high-yield and suitable for scale preparation.
出处
《国际药学研究杂志》
CAS
CSCD
北大核心
2015年第2期220-224,共5页
Journal of International Pharmaceutical Research
