合成路线:By condensation of styrene oxide (I) with 3,4-dimethoxyphenylethylamine (II) at 100 C to give N-(beta-hydroxy-beta-phenyl)ethyl-2-(3',4'-dimethoxyphenyl)ehtylamine (III),which is cyclized with H2SO4 to 1-phenyl-7,8-dimethoxy-2,3,4,5-tetrahydro-3,1-benzazepine (IV).This product is finally methylated with a refluxing mixture of formaldehyde and formic acid.
参考文献标题:Trimopam
文献作者:Castar,J.; Thorpe,P.
参考来源:Drugs Fut 1976,1(4),194
合成路线:By condensation of styrene oxide (I) with 3,4-dimethoxyphenylethylamine (II) at 100 C to give N-(beta-hydroxy-beta-phenyl)ethyl-2-(3',4'-dimethoxyphenyl)ehtylamine (III),which is cyclized with H2SO4 to 1-phenyl-7,8-dimethoxy-2,3,4,5-tetrahydro-3,1-benzazepine (IV).This product is finally methylated with a refluxing mixture of formaldehyde and formic acid.
合成路线:The bromination of labeled acetophenone (I) with Br2 and AlCl3 gives phenacyl bromide (II),which is condensed with N-[2-(3,4-dimethoxyphenyl)ethyl]-N-methylamine (III),yielding the 2-aminoacetophenone (IV).The reduction of (IV) with NaBH4 affords the secondary alcohol (V),which is finally cyclized by means of H2SO4 and trifluoroacetic acid to provide the target 3-benzazepine.
合成路线:The condensation of 2-chloro-3,4-dimethoxyphenylethylamine (I) with 4-methoxystyrene oxide (II) in refluxing THF gives the hydroxy phenylethylamine (III).The yield of this reaction is only 19%.In a better sequence (I) is heated with methyl 4-methoxymandelate (IV) to give the mandelamide (V),which is then reduced without purification by B2H6 in THF to give (III).The latter is cyclized by treatment with trifluoroacetic acid - sulfuric acid yielding 6-chloro-7,8-dimethoxy-1-(4-methoxyphenyl)-2,3,4,5-tetrahydro-(1H)-3-benzazepine (VI).Finally,this compound is demethylated by treatment with BBr3 in methylene chloride and treated with methanesulfonic acid.
合成路线:The bromination of 4-methoxystyrene (I) with Br2 gives the alpha,beta-dibromo derivative (II),which by selective debromination with potassium tert-butoxide yields the tert-butyl ether (III).The condensation of (III) with 2-(2-chloro-3,4-dimethoxyphenyl)ethylamine (IV) affords the secondary amine (V),which is deprotected with H2SO4 to provide the substituted ethanolamine (VI).The cyclization of (VI) by means of Ms-OH and trifluoroacetic acid gives the 3-benzazepine (VII),which is finally demethylated with BBr3 and treated with methanesulfonic acid to afford the target mesylate.
合成路线:The bromination of labeled 4'-methoxyacetophenone (I) with CuBr2 gives 4'-methoxyphenacyl bromide (II),which is reduced with NaBH4,yielding the carbinol (III).The protection of (III) with DHP affords the tetrahydropyranyl ether (IV),which is condensed with 2-(2-chloro-3,4-dimethoxyphenyl)ethylamine (V) and acidified to provide the aminoalcohol (VI).The cyclization of (VI) with MsOH and trifluoroacetic acid furnishes labeled 6-chloro-7,8-dimethoxy-1-(4-methoxyphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine (VII),which is finally demethylated with BBr3 and MsOH.
合成路线:The optical resolution of the racemic 6-chloro-7,8-dimethoxy-1-(4-methoxyphenyl)-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine (I) (+)- or (-)-dibenzoyltartaric acid gives the corresponding (R)-isomer (II),which is N-demethylated by means of BrCN to yield 6-chloro-7,8-dimethoxy-1(R)-(4-methoxyphenyl)-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine (III).Finally,this compound is fully demethylated by treatment with BBr3.The optical resolution can also be performed by treatment of racemic (III) with (+)- or (-)-dibenzoyltartaric acid.
参考文献标题:The chemistry and pharmacology of 3-benzazepines derivatives
文献作者:Hieble,J.P.; Wilson III,J.W.; Weinstock,J.
参考来源:Drugs Fut 1985,10(8),645
产品链接: CAS No. 56030-50-3›› 产品链接: CAS No.39624-66-3››