Dabigatran etexilate, BIBR-1048MS, BIBR-1048
达比加群酯Chemical Name: N-[2-[4-[N-(Hexyloxycarbonyl)amidino]phenylaminomethyl]-1-methyl-1H-benzimidazol-5-ylcarbonyl]-N-(2-pyridyl)-beta-alanine ethyl ester
CAS No. 211915-06-9
项目整合开发状态: Phase II
项目研究机构: Boehringer Ingelheim (Originator)
合成路线:4-Methylamino-3-nitrobenzoic acid (I) is converted into acid chloride (II) by using SOCl2,and subsequently condensed with ethyl 3-(2-pyridylamino)propionate (III) to produce amide (IV).Reduction of the nitro group of (IV) by catalytic hydrogenation yields the phenylenediamine (V).After acylation of diamine (V) with N-(4-cyanophenyl)glycine (VI),cyclization of the resulting amino amide in refluxing AcOH leads to benzimidazole (VII).The cyano group of (VII) is then transformed into amidine (VIII) employing the Pinner reaction.Finally,acylation of the amidino group of (VIII) with hexyl chloroformate gives rise to the target amidine carbamate derivative
📌 参考资料/链接：
参考文献标题:Disubstd.bicyclic heterocycles,their production and use as medicaments
文献作者:Hauel,N.; Wienen,W.; Ries,U.; Priepke,H.; Stassen,J.M.(Boehringer Ingelheim Pharma KG)
参考来源:DE 19706229; DE 19751939; EP 0966454; JP 2001509815; US 2003004181; US 6087380; US 6469039; WO 9837075
📄 详细内容
合成路线:4-Methylamino-3-nitrobenzoic acid (I) is converted into acid chloride (II) by using SOCl2,and subsequently condensed with ethyl 3-(2-pyridylamino)propionate (III) to produce amide (IV).Reduction of the nitro group of (IV) by catalytic hydrogenation yields the phenylenediamine (V).After acylation of diamine (V) with N-(4-cyanophenyl)glycine (VI),cyclization of the resulting amino amide in refluxing AcOH leads to benzimidazole (VII).The cyano group of (VII) is then transformed into amidine (VIII) employing the Pinner reaction.Finally,acylation of the amidino group of (VIII) with hexyl chloroformate gives rise to the target amidine carbamate derivative
参考文献标题:Structure-based design of novel potent nonpeptide thrombin inhibitors
文献作者:Hauel,N.H.; Nar,H.; Priepke,H.; Ries,U.J.; Stassen,J.M.; Wienen,W.
参考来源:J Med Chem 2002,45(9),1757
产品链接: CAS No. 211915-06-9››