|
【结 构 式】 
|
【分子编号】44071 【品名】(1R)-3-benzyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol 【CA登记号】 |
【 分 子 式 】C23H23NO2 【 分 子 量 】345.44116 【元素组成】C 79.97% H 6.71% N 4.05% O 9.26% |
合成路线1
该中间体在本合成路线中的序号：(VI)The optical resolution of the racemic 7,8-dimethoxy-3-methyl-1-phenyl-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 CN-Br to yield 7,8-dimethoxy-1(R)-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (III). Finally, this compound is fully demethylated by treatment with Ms-OH and methionine. An earlier alternative route to demethylation of (III) involves its conversion to the N-benzyl derivative (V) with benzyl bromide (IV), followed by demethylation with BBr3, yielding (VI), and final debenzylation with H2 over Pd/C.
| 【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) | 44063 | 7,8-dimethoxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine; 8-methoxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl methyl ether | C19H23NO2 | 详情 | 详情 | |
| (II) | 44068 | (1R)-7,8-dimethoxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine; (1R)-8-methoxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl methyl ether | C19H23NO2 | 详情 | 详情 | |
| (III) | 44069 | (1R)-7,8-dimethoxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine; (1R)-8-methoxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl methyl ether | C18H21NO2 | 详情 | 详情 | |
| (IV) | 12912 | 1-(Bromomethyl)benzene; Alpha-bromotoluene | 100-39-0 | C7H7Br | 详情 | 详情 |
| (V) | 44070 | (1R)-3-benzyl-7,8-dimethoxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine; (1R)-3-benzyl-8-methoxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl methyl ether | C25H27NO2 | 详情 | 详情 | |
| (VI) | 44071 | (1R)-3-benzyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol | C23H23NO2 | 详情 | 详情 |