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【结 构 式】 
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【分子编号】30512 【品名】3,3-dichloro-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one 【CA登记号】 |
【 分 子 式 】C10H9Cl2NO 【 分 子 量 】230.093 【元素组成】C 52.2% H 3.94% Cl 30.82% N 6.09% O 6.95% |
合成路线1
该中间体在本合成路线中的序号：(II)The reaction of 2,3,4,5-tetrahydro-1H-(1)benzazepin-2-one (I) with PCl5 in hot xylene gives 3,3-dichloro-2,3,4,5-tetrahydro-1H-(1)benzazepin-2-one (II), which is treated with sodium acetate and reduced with H2 over Pd/C in acetic acid yielding 3-chloro-2,3,4,5-tetrahydro-1H-(1)benzazepin-2-one (III). The reaction of (III) with sodium azide in DMSO affords 3-azido-2,3,4,5-tetrahydro-1H-(1)benzazepin-2-one (IV), which is condensed with benzyl bromoacetate (V) by means of NaH in DMF giving 3-azido-1-(benzyloxycarbonylmethyl)-2,3,4,5-tetrahydro-1H-(1)benzazepin-2-one (VI). The treatment of (VI) with Raney-Ni in ethanol-water yields 3-amino-1-(benzyloxycarbonylmethyl)-2,3,4,5-tetrahydro-1H-(1)benzazepin-2-one (VII), which is debenzylated by hydrogenation with H2 over Pd/C in ethanol affording 3-amino-1-(carboxymethyl)-2,3,4,5-tetrahydro-1H-(1)benzazepin-2-one (VIII). Finally, this compound is condensed with ethyl 3-benzylpyruvate (IX) by means of sodium cyanoborohydride in methanol acetic acid.
| 【1】 Watthey, J.W.H. (Novartis AG); Benzazepin-2-ones, process for their preparation, pharmaceutical preparations containing these compounds and the compounds for therapeutical use. EP 0072352; GB 2103614; JP 8338260 . |
| 【2】 Castaner, J.; Serradell, M.N.; CGS-14824 A. Drugs Fut 1984, 9, 5, 317. |
| 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) | 30511 | 1,3,4,5-tetrahydro-2H-1-benzazepin-2-one | C10H11NO | 详情 | 详情 | |
| (II) | 30512 | 3,3-dichloro-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one | C10H9Cl2NO | 详情 | 详情 | |
| (III) | 30513 | 3-chloro-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one | C10H10ClNO | 详情 | 详情 | |
| (IV) | 20891 | 3-azido-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one | C10H10N4O | 详情 | 详情 | |
| (V) | 12869 | benzyl 2-bromoacetate | 5437-45-6 | C9H9BrO2 | 详情 | 详情 |
| (VI) | 30514 | benzyl 2-(3-azido-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)acetate | C19H18N4O3 | 详情 | 详情 | |
| (VII) | 30515 | benzyl 2-(3-amino-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)acetate | C19H20N2O3 | 详情 | 详情 | |
| (VIII) | 30516 | 2-(3-amino-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)acetic acid | C12H14N2O3 | 详情 | 详情 | |
| (IX) | 20896 | Ethyl 2-oxo-4-phenylbutanoate; 2-Oxo-4-phenylbutyric acid ethyl ester | 64920-29-2 | C12H14O3 | 详情 | 详情 |