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【结 构 式】 
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【分子编号】15532 【品名】(1R,5S)-3,9-dimethyl-3,9-diazabicyclo[3.3.1]nonan-7-one oxime 【CA登记号】 |
【 分 子 式 】C9H17N3O 【 分 子 量 】183.2536 【元素组成】C 58.99% H 9.35% N 22.93% O 8.73% |
合成路线1
该中间体在本合成路线中的序号：(VI)The condensation of bromoacetaldehyde dimethyl acetal (I) with methylamine (II) by means of KOH in refluxing ethylene glycol gives bis(2,2-dimethoxyethyl)methylamine (III), which is cyclized with acetonedicarboxylic acid (IV) and more methylamine (II), yielding 3,9-dimethyl-3,9-diazabicyclo[3.3.1]nonan-7-one (V). The reaction of (V) with hydroxylamine affords the corresponding oxime (VI), which is reduced with H2 over RaNi in ethanol giving endo-3,9-dimethyl-3,9-diazabicyclo[3.3.1]nonan-7-amine (VII). Finally, this compound is condensed with 1H-indazole-3-carbonyl chloride (VIII) by means of dimethylaminopyridine (DMAP) in pyridine.
| 【1】 Castaner, J.; Rabasseda, X.; Mealy, N.; N-3389. Drugs Fut 1995, 20, 8, 780. |
| 【2】 Kikuchi, H.; Satoh, H.; Yahata, N.; Hagihara, K.; Hayakawa, T.; Mino, S.; Yanai, M. (Nisshin Flour Milling Co., Ltd.); Azabicyclo derivs. and their use as antiemetics. EP 0469449; JP 1993310749; US 5187166 . |
| 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) | 13183 | 2-Bromo-1,1-dimethoxyethane; 2-Bromo-1-methoxyethyl methyl ether; Bromoacetaldehyde dimethyl acetal | 7252-83-7 | C4H9BrO2 | 详情 | 详情 |
| (II) | 11021 | Methanamine; Methylamine | 74-89-5 | CH5N | 详情 | 详情 |
| (III) | 15529 | N-(2,2-dimethoxyethyl)-2,2-dimethoxy-N-methyl-1-ethanamine; N,N-bis(2,2-dimethoxyethyl)-N-methylamine; 2,2'-Methyliminobis-(acetaldehyde dimethyl acetal) | 70887-96-6 | C9H21NO4 | 详情 | 详情 |
| (IV) | 15530 | 1,3-Acetonedicarboxylic Acid; 3-Oxopentanedioic acid；3-oxoglutaric acid | 542-05-2 | C5H6O5 | 详情 | 详情 |
| (V) | 15531 | (1R,5S)-3,9-dimethyl-3,9-diazabicyclo[3.3.1]nonan-7-one | C9H16N2O | 详情 | 详情 | |
| (VI) | 15532 | (1R,5S)-3,9-dimethyl-3,9-diazabicyclo[3.3.1]nonan-7-one oxime | C9H17N3O | 详情 | 详情 | |
| (VII) | 15533 | (1R,5S)-3,9-dimethyl-3,9-diazabicyclo[3.3.1]non-7-ylamine; (1R,5S)-3,9-dimethyl-3,9-diazabicyclo[3.3.1]nonan-7-amine | C9H19N3 | 详情 | 详情 | |
| (VIII) | 15534 | 1H-indazole-3-carbonyl chloride | C8H5ClN2O | 详情 | 详情 |