ABR-5050
他喹莫德Chemical Name: 4-Hydroxy-N-[4-(trifluoromethyl)phenyl]-5-methoxy-N,1-dimethyl-2-oxo-1,2-dihydroquinoline-3-carboxamide
CAS No. 254964-60-8
项目整合开发状态: Preclinical
项目研究机构: Active Biotech (Originator)
合成路线:Reaction of 2,6-difluorobenzonitrile (I) with one equivalent of sodium methoxide gives rise to 2-fluoro-6-methoxybenzonitrile (II) which,upon further treatment with methylamine,furnishes the 2-methylamino derivative (III).Nitrile hydrolysis in (III) employing KOH in hot ethylene glycol yields the anthranilic acid (IV).This is converted into the isatoic anhydride (V) upon treatment with phosgene and NaHCO3.Reaction of (V) with sodium diethyl malonate produces the quinolinecarboxylate (VI).Hydrolysis of ester (VI) to the corresponding carboxylic acid (VII) is then performed with concentrated HCl in hot Ac2O.Acid (VII) is finally coupled with N-methyl p-(trifluoromethyl)aniline (VIII) by means of SOCl2 and Et3N to generate the target amide.
📌 参考资料/链接：
参考文献标题:Quinoline derivs.
文献作者:Fex,T.; Bjk,A.; J鰊sson,S.; Hedlund,G.(Active Biotech AB)
参考来源:EP 1095021; JP 2002520395; WO 0003991
📄 详细内容
合成路线:Reaction of 2,6-difluorobenzonitrile (I) with one equivalent of sodium methoxide gives rise to 2-fluoro-6-methoxybenzonitrile (II) which,upon further treatment with methylamine,furnishes the 2-methylamino derivative (III).Nitrile hydrolysis in (III) employing KOH in hot ethylene glycol yields the anthranilic acid (IV).This is converted into the isatoic anhydride (V) upon treatment with phosgene and NaHCO3.Reaction of (V) with sodium diethyl malonate produces the quinolinecarboxylate (VI).Hydrolysis of ester (VI) to the corresponding carboxylic acid (VII) is then performed with concentrated HCl in hot Ac2O.Acid (VII) is finally coupled with N-methyl p-(trifluoromethyl)aniline (VIII) by means of SOCl2 and Et3N to generate the target amide.
参考文献标题:Quinoline derivs.
文献作者:Fex,T.; Bjk,A.; J鰊sson,S.; Hedlund,G.(Active Biotech AB)
参考来源:US 6133285
产品链接: CAS No. 254964-60-8››