Mibefradil hydrochloride, Ro-40-5967/001, Ro-40-5967, Cerate 50, Posicor
米贝拉地尔米贝地尔Chemical Name: Methoxyacetic acid (1S,2S)-2-[2-[N-[3-(1H-benzimidazol-2-yl)propyl]-N-methylamino]ethyl]-6-fluoro-1-isopropyl-1,2,3,4-tetrahydro-2-naphthyl ester dihydrochloride
CAS No. 116666-63-8, 121039-16-5 (deleted CAS), 116644-53-2 (free base)
项目整合开发状态: Withdrawn-1998
项目研究机构: Roche (Originator), Asta Medica (Licensee)
合成路线:The condensation of 4-(1-benzyloxy-N-methylformamido)butyric acid (I) with o-phenylenediamine (II) and isobutyl chloroformate (III) by means of triethylamine gives N-[3-[N-(2-aminophenyl)carbamoyl]propyl]-N-methylcarbamic acid benzyl ester (IV),which is cyclized by means of p-toluenesulfonic acid in refluxing toluene to the benzimidazole derivative (V).Hydrogenation of (V) with H2 over Pd/C in methanol affords 2-[3-(methylamino)propyl]benzimidazole (VI),which is condensed with the chiral p-toluenesulfonate (VII) by heating at 120 C to give the chiral tetrahydronaphthol (VIII).Finally,this alcohol is esterified with 2-methoxyacetyl chloride and ethyl diisopropylamine in chloroform.
📌 参考资料/链接：
参考文献标题:Tetrahydronaphthalene derivs.and medicines containing them
文献作者:Branca,Q.; Jaunin,R.; M鋜ki,H.P.; Marti,F.; Ramuz,H.(F.Hoffmann-La Roche AG)
参考来源:EP 0268148; JP 1988139171; US 4808605
📄 详细内容
合成路线:The condensation of 4-(1-benzyloxy-N-methylformamido)butyric acid (I) with o-phenylenediamine (II) and isobutyl chloroformate (III) by means of triethylamine gives N-[3-[N-(2-aminophenyl)carbamoyl]propyl]-N-methylcarbamic acid benzyl ester (IV),which is cyclized by means of p-toluenesulfonic acid in refluxing toluene to the benzimidazole derivative (V).Hydrogenation of (V) with H2 over Pd/C in methanol affords 2-[3-(methylamino)propyl]benzimidazole (VI),which is condensed with the chiral p-toluenesulfonate (VII) by heating at 120 C to give the chiral tetrahydronaphthol (VIII).Finally,this alcohol is esterified with 2-methoxyacetyl chloride and ethyl diisopropylamine in chloroform.
参考文献标题:Mibefradil Hydrochloride
文献作者:Merlos,M.; Castar,J.; Casa,A.; Graul,A.
参考来源:Drugs Fut 1997,22(10),1091
产品链接: CAS No. 116666-63-8›› 产品链接: CAS No.116644-53-2››