7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one -Drug Synthesis Database

【结构式】

【分子编号】24285

【品名】7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one

【CA登记号】

【分子式】C₁₂H₁₃NO₃

【分子量】219.24016

【元素组成】C 65.74% H 5.98% N 6.39% O 21.89%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(V)

The reaction of 3,4-dimethoxyphenylacetic acid (I) with SOCl2 in methylene chloride gives the corresponding acyl chloride (II), which is treated with aminoacetaldehyde dimethylacetal (III) and triethylamine in methylene chloride yielding N-(2,2-diethoxyethyl)-3,4-dimethoxyphenylacetamide (IV). The cyclization of (IV) by means of HCl in acetic acid atfords 7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one (V), which is alkylated with 1-bromo-3-chloro propane (VI) by means of potassium tert-butoxide in DMSO to give 3-(3-chloropropyl)-7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one (VII). The reaction of (VII) with N-methyl-2-(3,4-dimethoxyphenyl)ethylamine (VIII) at 100 C affords 7,8-dimethoxy-3-[3-[N-methyl-N-[2-(3,4-dimethoxyphenyl)ethyl]amino]propyl]-1,3-dihydro-2H-3-benzazepin-2-one (IX), which is finally hydrogenated with H2 over Pd/C in acetic acid.

参考文献中间体

合成目标

【1】 Reiffen, M.; et al. (Dr. Karl Thomae GmbH); Benzazepines, process for their preparation and their application as pharmaceutical preparations. DE 3119874; EP 0065229; GB 2099425; JP 57193462 .
【2】 Reiffen, M. (Dr. Karl Thomae GmbH); Process for the prepaation of benzazepine derivatives. CA 1207764; DD 215541; DE 3242345 .
【3】 Prous, J.; Castaner, J.; Ul-FS-49. Drugs Fut 1985, 10, 8, 639.

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)	24049	2-(3,4-dimethoxyphenyl)acetic acid	93-40-3	C₁₀H₁₂O₄	详情	详情
(II)	20594	2-(3,4-dimethoxyphenyl)acetyl chloride		C₁₀H₁₁ClO₃	详情	详情
(III)	10331	2,2-Diethoxy-1-ethanamine; 2,2-Diethoxyethylamine; Aminoacetaldehyde diethyl acetal	645-36-3	C₆H₁₅NO₂	详情	详情
(IV)	24284	N-(2,2-diethoxyethyl)-2-(3,4-dimethoxyphenyl)acetamide		C₁₆H₂₅NO₅	详情	详情
(V)	24285	7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one		C₁₂H₁₃NO₃	详情	详情
(VI)	10358	1-Bromo-3-chloropropane	109-70-6	C₃H₆BrCl	详情	详情
(VII)	18398	1-(tert-butyl) 3-ethyl (3R,4R)-4-phenyl-1,3-piperidinedicarboxylate		C₁₉H₂₇NO₄	详情	详情
(VIII)	24899	3-(3-chloropropyl)-7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one		C₁₅H₁₈ClNO₃	详情	详情
(IX)	24901	3-[3-[(3,4-dimethoxyphenethyl)(methyl)amino]propyl]-7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one		C₂₆H₃₄N₂O₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

The condensation of 3,4-dimethoxyphenyacetic acid (I) with 2-aminoacetaldehyde diethylacetal (II) by means of 1,1'-carbonyldiimidazole (CDI) in CHCl3 gives N-(2,2-diethoxyethyl)-3,4-dimelhoxyphenylacetamide (III), which is cyclized by means of 48% aqueous HBr yielding 1,3-dihydro-7,8-dimethoxy-2H-3-benzazepin-2-one (IV). The reaction of (IV) with triethyloxonium tetrafluoroborate (V) in methylene chloride affords 2-ethoxy-7,8-dimethoxy-1H-3-benzazepine (VI), which is finally treated with ammonium chloride in refluxing methanol.

参考文献中间体

合成目标

【1】 Paget, C.J. Jr.; Ruffolo, R.R. Jr. (Eli Lilly and Company); Benzazepine derivs.. EP 0116444; ES 8602681; ES 8801215; GB 2134519 .
【2】 Prous, J.; Castaner, J.; LY-127210. Drugs Fut 1986, 11, 9, 748.

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)	24049	2-(3,4-dimethoxyphenyl)acetic acid	93-40-3	C₁₀H₁₂O₄	详情	详情
(II)	10331	2,2-Diethoxy-1-ethanamine; 2,2-Diethoxyethylamine; Aminoacetaldehyde diethyl acetal	645-36-3	C₆H₁₅NO₂	详情	详情
(III)	24284	N-(2,2-diethoxyethyl)-2-(3,4-dimethoxyphenyl)acetamide		C₁₆H₂₅NO₅	详情	详情
(IV)	24285	7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one		C₁₂H₁₃NO₃	详情	详情
(VI)	24287	2-ethoxy-7,8-dimethoxy-1H-3-benzazepine		C₁₄H₁₇NO₃	详情	详情

Extended Information