Devazepide, MK-329, L-364718, Devacade
地伐西匹Chemical Name: 3S-(-)-N-(2,3-Dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl)-1H-indole-2-carboxamide; 3(S)-(-)-1,3-Dihydro-3-(2-indolecarbonylamino)-1-methyl-5-phenyl-2H-[1,4]benzodiazepin-2-one
CAS No. 103420-77-5
项目整合开发状态: Phase II
项目研究机构: Merck & Co. (Originator), Panos Therapeutics (Licensee), ML Laboratories (Codevelopment)
合成路线:2-Aminobenzophenone (I) is acylated with bromoacetyl bromide followed by reaction with ammonia to form the [1,4]benzodiazepine.N1-Methylation produces 1,3-dihydro-1-methyl-5-phenyl-2H-[1,4]benzodiazepin-2-one (II).Treatment with isoamyl nitrate and t-BuOK gives an oxime,which is reduced by catalytic hydrogenation to racemic 3-amino-benzodiazepine (III),which is isolated as the crystalline benzenesulfonic acid salt.Crystallization-induced asymmetric transformation yields 3(S)-(-)-3-amino-1,3-dihydro-1-methyl-5-phenyl-2H-[1,4]benzodiazepin-2-one (IV).Acylation with indole-2-carbonylimidazolide produces MK-329.
📌 参考资料/链接：
参考文献标题:MK-329
文献作者:Freidinger,R.M.; Berlin,R.G.
参考来源:Drugs Fut 1989,14(9),862
📄 详细内容
合成路线:2-Aminobenzophenone (I) is acylated with bromoacetyl bromide followed by reaction with ammonia to form the [1,4]benzodiazepine.N1-Methylation produces 1,3-dihydro-1-methyl-5-phenyl-2H-[1,4]benzodiazepin-2-one (II).Treatment with isoamyl nitrate and t-BuOK gives an oxime,which is reduced by catalytic hydrogenation to racemic 3-amino-benzodiazepine (III),which is isolated as the crystalline benzenesulfonic acid salt.Crystallization-induced asymmetric transformation yields 3(S)-(-)-3-amino-1,3-dihydro-1-methyl-5-phenyl-2H-[1,4]benzodiazepin-2-one (IV).Acylation with indole-2-carbonylimidazolide produces MK-329.
参考文献标题:Synthesis and resolution of 3-amino-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-ones
文献作者:Veber,D.F.; Freidinger,R.M.; Hirshfield,J.; Rittle,K.E.; Springer,J.P.; DiPardo,R.M.; Bock,M.G.; Evans,B.E.
参考来源:J Org Chem 1987,523232
合成路线:2-Aminobenzophenone (I) is acylated with bromoacetyl bromide followed by reaction with ammonia to form the [1,4]benzodiazepine.N1-Methylation produces 1,3-dihydro-1-methyl-5-phenyl-2H-[1,4]benzodiazepin-2-one (II).Treatment with isoamyl nitrate and t-BuOK gives an oxime,which is reduced by catalytic hydrogenation to racemic 3-amino-benzodiazepine (III),which is isolated as the crystalline benzenesulfonic acid salt.Crystallization-induced asymmetric transformation yields 3(S)-(-)-3-amino-1,3-dihydro-1-methyl-5-phenyl-2H-[1,4]benzodiazepin-2-one (IV).Acylation with indole-2-carbonylimidazolide produces MK-329.
参考文献标题:Crystallization-induced asymmetric transformation: Stereospecific synthesis of a potent peripheral CCK antagonis
文献作者:Reider,P.J.; Davis,P.; Grabowski,E.J.J.; Hughes,D.L.
参考来源:J Org Chem 1987,52955
产品链接: CAS No. 103420-77-5››