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【结 构 式】

【分子编号】36621

【品名】(3aS,9bR)-11-methoxy-3-methyl-2,3,3a,4,5,9b-hexahydro-1H-naphtho[1,2-a][3]benzazepin-12-yl methyl ether; (3aS,9bR)-11,12-dimethoxy-3-methyl-2,3,3a,4,5,9b-hexahydro-1H-naphtho[1,2-a][3]benzazepine

【CA登记号】

【 分 子 式 】C21H25NO2

【 分 子 量 】323.43504

【元素组成】C 77.99% H 7.79% N 4.33% O 9.89%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(V)

The condensation of N-[2-(3,4-dimethoxyphenyl)ethyl]-N-methylamine (I) with 2-bromo-1-tetralone (II) by means of K2CO3 in DMF gives the tertiary amine (III), which is reduced with NaBH4 in ethanol to the hydroxyamine (IV). The cyclization of (IV) by means of methanesulfonic acid yields a mixture of cis and trans tetracyclic compounds that is separated by chromatography. The desired trans isomer (V) is monodemethylated by means of EtS-Na in DMF affording a mixture of 11-methoxy,12-hydroxy and 12-methoxy-11-hydroxy compounds that is separated by crystallization. The desired 12-methoxy-11-hydroxy compound (VI) is dehydroxylated by means of 5-chloro-1-phenyltetrazole (CPT) and NaH in hot DMF giving the 12-methoxy compound (VII), which is chlorinated with SO2Cl2 in dichloromethane to afford the racemic 11-chloro-12-methoxy compound rac-(VIII). Optical resolution of rac-(VIII) with (+)-di-p-toluoyl-D-tartaric acid [(+)-DPT] gives (-)(6aS,13bR)(VIII), which is finally demethylated to the target compound with 48% HBr in refluxing acetic acid.

1 Berger, J.G.; et al.; Synthesis and receptor affinities of some conformationally restricted analogues of the dopamine D1 selective ligand (5R)-8-chloro-2,3,4, 5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol. J Med Chem 1989, 32, 8, 1913-21.
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) 18938 2-(3,4-dimethoxyphenyl)-N-methyl-1-ethanamine; N-(3,4-dimethoxyphenethyl)-N-methylamine 3490-06-0 C11H17NO2 详情 详情
(II) 20721 2-bromo-3,4-dihydro-1(2H)-naphthalenone C10H9BrO 详情 详情
(III) 36619 2-[(3,4-dimethoxyphenethyl)(methyl)amino]-3,4-dihydro-1(2H)-naphthalenone C21H25NO3 详情 详情
(IV) 36620 2-[(3,4-dimethoxyphenethyl)(methyl)amino]-1,2,3,4-tetrahydro-1-naphthalenol C21H27NO3 详情 详情
(V) 36621 (3aS,9bR)-11-methoxy-3-methyl-2,3,3a,4,5,9b-hexahydro-1H-naphtho[1,2-a][3]benzazepin-12-yl methyl ether; (3aS,9bR)-11,12-dimethoxy-3-methyl-2,3,3a,4,5,9b-hexahydro-1H-naphtho[1,2-a][3]benzazepine C21H25NO2 详情 详情
(VI) 36622 (3aS,9bR)-11-methoxy-3-methyl-2,3,3a,4,5,9b-hexahydro-1H-naphtho[1,2-a][3]benzazepin-12-ol C20H23NO2 详情 详情
(VII) 36623 (3aS,9bR)-11-methoxy-3-methyl-2,3,3a,4,5,9b-hexahydro-1H-naphtho[1,2-a][3]benzazepine; (3aS,9bR)-3-methyl-2,3,3a,4,5,9b-hexahydro-1H-naphtho[1,2-a][3]benzazepin-11-yl methyl ether C20H23NO 详情 详情
(VIII) 31779 (3aS,9bR)-12-chloro-11-methoxy-3-methyl-2,3,3a,4,5,9b-hexahydro-1H-naphtho[1,2-a][3]benzazepine; (3aS,9bR)-12-chloro-3-methyl-2,3,3a,4,5,9b-hexahydro-1H-naphtho[1,2-a][3]benzazepin-11-yl methyl ether C20H22ClNO 详情 详情
Extended Information