2-[(3,4-dimethoxyphenethyl)amino]-1-phenyl-1-ethanol -Drug Synthesis Database

【结构式】

【分子编号】39206

【品名】2-[(3,4-dimethoxyphenethyl)amino]-1-phenyl-1-ethanol

【CA登记号】

【分子式】C₁₈H₂₃NO₃

【分子量】301.38556

【元素组成】C 71.73% H 7.69% N 4.65% O 15.93%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(III)

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.

参考文献中间体

合成目标

【1】 Hieble, J.P.; Wilson III, J.W.; Weinstock, J.; The chemistry and pharmacology of 3-benzazepines derivatives. Drugs Fut 1985, 10, 8, 645.
【2】 Walter, L.A.; Chang, W.K. (Schering Corp.); Novel benzazepines. US 3393192 .
【3】 Castaner, J.; Thorpe, P.; Trimopam. Drugs Fut 1976, 1, 4, 194.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	23017	2-phenyloxirane	96-09-3	C₈H₈O	详情	详情
(II)	10098	2-(3,4-Dimethoxyphenyl)-1-ethanamine; 3,4-Dimethoxyphenethylamine; 2-(3,4-Dimethoxyphenyl)ethylamine	120-20-7	C₁₀H₁₅NO₂	详情	详情
(III)	39206	2-[(3,4-dimethoxyphenethyl)amino]-1-phenyl-1-ethanol		C₁₈H₂₃NO₃	详情	详情
(IV)	39207	7,8-dimethoxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine; 8-methoxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl methyl ether		C₁₈H₂₁NO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

The condensation of 3,4-dimethoxyphenethylamine (I) with styrene oxide (II) by heating at 100 C gives N-[2-(3,4-dimethoxyphenyl)ethyl]-2-phenyl-2-hydroxyethylamine (III), which can be cyclized with H2SO4 in refluxing trifluoroacetic acid yielding 2,3,4,5-tetrahydro-7,8-dimethoxy-1-phenyl-1H-3-benzazepine (IV). Finally, intermediate (IV) is demethylated with refluxing 48% HBr (III) can also by cyclized and demethylated simultaneously by refluxing with 48% HBr.

参考文献中间体

合成目标

【1】 Kaiser, C.; et al.; DE 2629887 .
【2】 Hieble, J.P.; Wilson III, J.W.; Weinstock, J.; The chemistry and pharmacology of 3-benzazepines derivatives. Drugs Fut 1985, 10, 8, 645.
【3】 Castaner, J.; Hillier, K.; SKF-38393. Drugs Fut 1980, 5, 10, 507.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	10098	2-(3,4-Dimethoxyphenyl)-1-ethanamine; 3,4-Dimethoxyphenethylamine; 2-(3,4-Dimethoxyphenyl)ethylamine	120-20-7	C₁₀H₁₅NO₂	详情	详情
(II)	23017	2-phenyloxirane	96-09-3	C₈H₈O	详情	详情
(III)	39206	2-[(3,4-dimethoxyphenethyl)amino]-1-phenyl-1-ethanol		C₁₈H₂₃NO₃	详情	详情
(IV)	39207	7,8-dimethoxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine; 8-methoxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl methyl ether		C₁₈H₂₁NO₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(VI)

The bromination of labeled acetophenone (I) with Br2 and AlCl3 gives the phenacyl bromide (II), which is reduced with NaBH4, yielding 2-bromo-1-phenylethanol (III). The condensation of (III) with N-benzyl-N-[2-(3,4-dimethoxyphenyl)ethyl]amine (IV) affords the tertiary amine (V), which is debenzylated by hydrogenolysis with H2 over Pd/C to provide the substituted ethanolamine (VI). Finally, this compound is cyclized and demethylated by treatment with 48% HBr to provide the target benzazepine.

参考文献中间体

合成目标

【1】 Hieble, J.P.; Wilson III, J.W.; Weinstock, J.; The chemistry and pharmacology of 3-benzazepines derivatives. Drugs Fut 1985, 10, 8, 645.
【2】 Bass, L.S.; Dandridge, P.A.; Setler, P.E.; Sarau, H.M.; Garvey, E.; Clardy, J.; Hanhn, R.A.; Kaiser, C.; Absolute stereochemistry and dopaminergic activity of enantiomers of 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine. J Med Chem 1982, 25, 6, 697-703.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	10317	Acetophenone	98-86-2	C₈H₈O	详情	详情
(I)	44572	acetophenone		C₈H₈O	详情	详情
(II)	10315	2-Bromo-1-phenyl-ethanone; 2-Bromo-1-phenyl-1-ethanone	70-11-1	C₈H₇BrO	详情	详情
(II)	44573	2-bromo-1-phenyl-1-ethanone		C₈H₇BrO	详情	详情
(III)	44060	2-bromo-1-phenyl-1-ethanol		C₈H₉BrO	详情	详情
(III)	44632	2-bromo-1-phenyl-1-ethanol		C₈H₉BrO	详情	详情
(IV)	44061	N-benzyl-2-(3,4-dimethoxyphenyl)-1-ethanamine; N-benzyl-N-(3,4-dimethoxyphenethyl)amine		C₁₇H₂₁NO₂	详情	详情
(V)	44062	2-[benzyl(3,4-dimethoxyphenethyl)amino]-1-phenyl-1-ethanol		C₂₅H₂₉NO₃	详情	详情
(V)	44633	2-[benzyl(3,4-dimethoxyphenethyl)amino]-1-phenyl-1-ethanol		C₂₅H₂₉NO₃	详情	详情
(VI)	39206	2-[(3,4-dimethoxyphenethyl)amino]-1-phenyl-1-ethanol		C₁₈H₂₃NO₃	详情	详情
(VI)	44634	2-[(3,4-dimethoxyphenethyl)amino]-1-phenyl-1-ethanol		C₁₈H₂₃NO₃	详情	详情

Extended Information