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项目整合精选>>>Dilevalol, Sch-19927, Unicard, Dilevalon, Unicarde, Levadil
Dilevalol, Sch-19927, Unicard, Dilevalon, Unicarde, Levadil
地瓦洛尔Chemical Name: [R-(R*,R*)-2-Hydroxy-5-[1-hydroxy-2-[(4-phenyl-2-butyl)amino]ethyl]benzamide; [R-(R*,R*)]-2-Hydroxy-5-[1-hydroxy-2-[(1-methyl-3-phenylpropyl)amino]ethyl]benzamide; (-)-5-[(1R)-1-Hydroxy-2-[(1R)-1-methyl-3-phenylpropylamino]ethyl]salicylamide
CAS No. 75659-07-3, 75659-08-4 (monoHCl)
项目整合开发状态: Withdrawn-1990
项目研究机构: Schering-Plough (Originator), Shionogi (Licensee)
合成路线:The reaction of 5-acetylsalicylamide (I) with benzyl chloride (II) by means of sodium methoxide in hot DMF gives 4-benzyloxy-3-carbamoylacetophenone (III),which by bromination with Br2 in refluxing CHCl3 is converted into 4-benzyloxy-3-carbamoylphenacyl bromide (IV).The condensation of (IV) with N-(4-phenyl-2-butyl)benzylamine (V) (prepared from benzylamine (VI) and 4-phenyl-2-butanone (VII),p-toluenesulfonic acid and NaBH4 in benzene -methanol) by means of K2CO3 in DMF yields 2-benzyloxy-5-[N-benzyl-N-(1-methyl-3-phenylpropyl)glycyl]benzamide (VIII),which is reduced with NaBH4 in ethanol to afford 2-benzyloxy-5-[1-hydroxy-2-[(4-phenyl-2-butyl)-N-benzylamino]ethyl]benzamide (IX).Finally,this compound is debenzylated by hydrogenolysis with H2 over Pd/C in ethanol.The separation into its optical isomers is performed by conventional methods.
📌 参考资料/链接：
参考文献标题:A phenylalkylaminoethylsalicylamide,its preparation and pharmaceutical compositions containing it
文献作者:Gold,E.H.; Chang,W.(Schering Corp.)
参考来源:CA 1151211; DD 150457; EP 0009702; JP 55055147; ZA 7904872
📄 详细内容
合成路线:The reaction of 5-acetylsalicylamide (I) with benzyl chloride (II) by means of sodium methoxide in hot DMF gives 4-benzyloxy-3-carbamoylacetophenone (III),which by bromination with Br2 in refluxing CHCl3 is converted into 4-benzyloxy-3-carbamoylphenacyl bromide (IV).The condensation of (IV) with N-(4-phenyl-2-butyl)benzylamine (V) (prepared from benzylamine (VI) and 4-phenyl-2-butanone (VII),p-toluenesulfonic acid and NaBH4 in benzene -methanol) by means of K2CO3 in DMF yields 2-benzyloxy-5-[N-benzyl-N-(1-methyl-3-phenylpropyl)glycyl]benzamide (VIII),which is reduced with NaBH4 in ethanol to afford 2-benzyloxy-5-[1-hydroxy-2-[(4-phenyl-2-butyl)-N-benzylamino]ethyl]benzamide (IX).Finally,this compound is debenzylated by hydrogenolysis with H2 over Pd/C in ethanol.The separation into its optical isomers is performed by conventional methods.
参考文献标题:Diastereoisomers of 5-(1-hydroxy-2-(1-methyl-3-phenylpropylamino)ethyl)salicylamide
文献作者:Gold,E.H.; Chang,W.(Schering Biotech Corp.)
参考来源:US 4173583
合成路线:The reaction of 5-acetylsalicylamide (I) with benzyl chloride (II) by means of sodium methoxide in hot DMF gives 4-benzyloxy-3-carbamoylacetophenone (III),which by bromination with Br2 in refluxing CHCl3 is converted into 4-benzyloxy-3-carbamoylphenacyl bromide (IV).The condensation of (IV) with N-(4-phenyl-2-butyl)benzylamine (V) (prepared from benzylamine (VI) and 4-phenyl-2-butanone (VII),p-toluenesulfonic acid and NaBH4 in benzene -methanol) by means of K2CO3 in DMF yields 2-benzyloxy-5-[N-benzyl-N-(1-methyl-3-phenylpropyl)glycyl]benzamide (VIII),which is reduced with NaBH4 in ethanol to afford 2-benzyloxy-5-[1-hydroxy-2-[(4-phenyl-2-butyl)-N-benzylamino]ethyl]benzamide (IX).Finally,this compound is debenzylated by hydrogenolysis with H2 over Pd/C in ethanol.The separation into its optical isomers is performed by conventional methods.
参考文献标题:Sch-19,927
文献作者:Serradell,M.N.; Castar,J.; Weetman,D.F.; Blancafort,P.
参考来源:Drugs Fut 1982,7(11),815
产品链接: CAS No. 75659-07-3›› 产品链接: CAS No.75659-08-4››