T-705

法匹拉韦Chemical Name: 6-Fluoro-3-hydroxypyrazine-2-carboxamide
CAS No. 259793-96-9
项目整合开发状态: Preclinical
项目研究机构: Toyama (Originator)
合成路线:Treatment of methyl 6-bromo-3-amino-2-pyrazinecarboxylate (I) with sodium nitrite (NaNO2) in H2SO4 followed by refluxing in MeOH yields methoxy derivative (II),whose Br group is converted into an amino functionality by treatment with benzophenone-imine,tris(dibenzylidene-acetone)dipalladium,(S)-(-)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl and sodium tert-butoxide in toluene; a final treatment with HCl in THF affords amino compound (III).Treatment of methyl carboxylate of (III) with NH3(g) in MeOH gives carboxamide (IV),which is then treated with pyridine hydrofluoride and NaNO2 to furnish fluoro derivative (V).Finally,the target product is obtained by conversion of the methoxy group of (V) into a hydroxy group by reaction with NaI and trimethylsilyl chloride (TMSCl) in acetonitrile.