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【结 构 式】 
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【分子编号】41810 【品名】1,2,3,4-tetrahydro-5H-1-benzazepin-5-one 【CA登记号】 |
【 分 子 式 】C10H11NO 【 分 子 量 】161.20348 【元素组成】C 74.51% H 6.88% N 8.69% O 9.92% |
合成路线1
该中间体在本合成路线中的序号：(I)Acylation of 2,3,4,5-tetrahydro-1H-1-benzazepin-5-one (I) with 4-nitrobenzoyl chloride (II) by means of TEA in CH2Cl2 gives 1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-1-benzazepin-5-one (III), which is hydrogenated with H2 over Raney-Ni in MeOH, yielding the corresponding amine derivative (IV). Acylation of (IV) with biphenyl-2-carboxylic acid (V) by means of oxalyl chloride in CH2Cl2 affords the expected amide (VI) which is brominated with either Br2 or CuBr2, providing the alpha-bromo ketone (VII). This ketone (VII) is cyclized with acetamidine hydrochloride (VIII) by means of K2CO3 in MeCN, furnishing a mixture of conivaptan and oxazolo[4,5-d][1]benzodiazepine compound. Finally, conivaptan is separated by column chromatography over silica gel and is treated with 4N HCl to provide the desired hydrochloride.
| 【1】 Castañer, R.M.; Norman, P.; Rabasseda, X.; Leeson, P.A.; Castañer, J.; Conivaptan Hydrochloride. Drugs Fut 2000, 25, 11, 1121. |
| 【2】 Tanaka, A.; Koshio, H.; Taniguchi, N.; Matsuhisa, A.; Sakamoto, K.; Yamazaki, A.; Yatsu, T. (Yamanouchi Pharmaceutical Co., Ltd.); Fused benzazepine deriv. and pharmaceutical compsn. containing the same. EP 0709386; JP 1995505056; US 5723606; WO 9503305 . |
| 【3】 Koshio, H.; Taniguchi, N.; Tanaka, A.; Yatsu, T.; Matsuhisa, A.; Nonpeptide arginine vasopressin antagonists for both V1A and V2 receptors: Synthesis and pharmacological properties of 4'-(1,4,5,6-tetrahydroimidazo[4,5-d][1]benzoazepine-6-carbonyl)benzanilide derivatives and 4'-(5,6-dihydro-4H-thiazolo[5,4-d][1]benzoaze. Chem Pharm Bull 2000, 48, 1, 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) | 41810 | 1,2,3,4-tetrahydro-5H-1-benzazepin-5-one | C10H11NO | 详情 | 详情 | |
| (II) | 18941 | p-nitrobenzoyl chloride; 4-nitrobenzoyl chloride | 122-04-3 | C7H4ClNO3 | 详情 | 详情 |
| (III) | 41811 | 1-(4-nitrobenzoyl)-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one | C17H14N2O4 | 详情 | 详情 | |
| (IV) | 41812 | 1-(4-aminobenzoyl)-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one | C17H16N2O2 | 详情 | 详情 | |
| (V) | 18505 | [1,1'-biphenyl]-2-carboxylic acid | 947-84-2 | C13H10O2 | 详情 | 详情 |
| (VI) | 41813 | N-[4-[(5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)carbonyl]phenyl][1,1'-biphenyl]-2-carboxamide | C30H24N2O3 | 详情 | 详情 | |
| (VII) | 41814 | N-[4-[(4-bromo-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)carbonyl]phenyl][1,1'-biphenyl]-2-carboxamide | C30H23BrN2O3 | 详情 | 详情 | |
| (VIII) | 15866 | ethanimidamide | C2H6N2 | 详情 | 详情 |