|
【结 构 式】 
|
【药物名称】T-705；Favipiravir 【化学名称】6-Fluoro-3-hydroxypyrazine-2-carboxamide 【CA登记号】259793-96-9 【 分 子 式 】C5H4FN3O2 【 分 子 量 】157.10493 |
【开发单位】Toyama (Originator) 【药理作用】ANTIINFECTIVE THERAPY, Anti-Influenza Virus Drugs, Antiviral Drugs |
合成路线1
Alternatively, regioselective fluoride group substitution in 3,6-difluoropyrazine-2-carbonitrile (VI) using KOAc in the presence of NH4OH leads to the corresponding 3-hydroxypyrazine derivative (VII), isolated as the dicyclohexylamine salt by treatment with DCHA in DMF/H2O. Finally, nitrile (VII) is hydrolyzed using NaOH/H2O2 followed by treatment with HCl .
| 【1】 Furuta, Y., Egawa, H. (Toyama Chemical Co., Ltd.). Nitrogenous heterocyclic carboxamide derivatives or salts thereof and antiviral agents containing both. EP 1112743, US 2002013316, US 6787544, WO 2000010569. |
合成路线2
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.
| 【1】 Furuta, Y.; Egawa, H. (Toyama Chemical Co., Ltd.); Nitrogenous heterocyclic carboxamide derivs. or salts thereof and antiviral agents containing both. EP 1112743; WO 0010569 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 48924 | Methyl 3-amino-6-bromo-2-pyrazinecarboxylate | C6H6BrN3O2 | 详情 | 详情 | |
| (II) | 48925 | methyl 6-bromo-3-methoxy-2-pyrazinecarboxylate | C7H7BrN2O3 | 详情 | 详情 | |
| (III) | 32024 | diphenylmethanimine | 1013-88-3 | C13H11N | 详情 | 详情 |
| (IV) | 48926 | methyl 6-amino-3-methoxy-2-pyrazinecarboxylate | C7H9N3O3 | 详情 | 详情 | |
| (V) | 48927 | 6-amino-3-methoxy-2-pyrazinecarboxamide | C6H8N4O2 | 详情 | 详情 | |
| (VI) | 48928 | 6-fluoro-3-methoxy-2-pyrazinecarboxamide | C6H6FN3O2 | 详情 | 详情 |