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【结 构 式】 
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【分子编号】14651 【品名】(6S)-6-[propyl[2-(2-thienyl)ethyl]amino]-5,6,7,8-tetrahydro-1-naphthalenol 【CA登记号】 |
【 分 子 式 】C19H25NOS 【 分 子 量 】315.47964 【元素组成】C 72.34% H 7.99% N 4.44% O 5.07% S 10.16% |
合成路线1
该中间体在本合成路线中的序号：(VII)The overall synthetic approach to N-0923 is described: Methylation of 1,6-dihydroxynaphthalene (I) with dimethyl sulfate provides 1,6-dimethoxynaphthalene (II), which is converted to 5-methoxy-2-tetralone (III) by reduction with sodium in ethanol. Reductive amination of (III) with propylamine results in the racemic 5-methoxy-2-N-propylaminotetralin (IV), from which the (-)-enantiomer (V) is obtained by fractional crystallization of the dibenzoyl-L-tartaric acid (L-DBTA) salt. Demethylation with aqueous hydrobromic acid affords (-)-(S)-5-hydroxy-2-N-propylaminotetralin (VI), which is reductively alkylated with thienylacetic acid in the presence of trimethylaminoborane to (-)-(S)-5-hydroxy-2-[N-propyl-N-[2-(2-thienyl)ethyl]amino]tetralin (VII). Treatment with anhydrous hydrogen chloride in ether provides N-0923.
| 【1】 Evans, D.; Grey, T.F.; Richards, K.E.; Ames, D.E.; Islip, P.J.; Synthesis of alkoxy-1,2,3,4-tetrahydronaphthalene derivatives. J Chem Soc 1965, 2636-41. |
| 【2】 Wynberg, H.; Ten Hoeve, W.; Ten Hoeve, W., Wynberg, H. The design of resolving agents. Chiral phosphoric acids. J Org Chem 1985, 50, 4508-14. |
| 【3】 Manimaran, T.; Impastato, F.J. (Ethyl Corporation); Resolution of racemic mixtures. US 4968837 . |
| 【4】 Cusack, N.J.; Peck, J.V.; N-0923. Drugs Fut 1993, 18, 11, 1005. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 22959 | 2-(2-thienyl)acetic acid | 1918-77-0 | C6H6O2S | 详情 | 详情 | |
| (I) | 14645 | 1,6-naphthalenediol; 1,6-Dihydroxynaphthalene | 575-44-0 | C10H8O2 | 详情 | 详情 |
| (II) | 14646 | 5-methoxy-2-naphthyl methyl ether; 1,6-dimethoxynaphthalene | 3900-49-0 | C12H12O2 | 详情 | 详情 |
| (III) | 14647 | 5-methoxy-3,4-dihydro-2(1H)-naphthalenone | 32940-15-1 | C11H12O2 | 详情 | 详情 |
| (IV) | 14648 | N-(5-methoxy-1,2,3,4-tetrahydro-2-naphthalenyl)-N-propylamine; 5-methoxy-N-propyl-1,2,3,4-tetrahydro-2-naphthalenamine | C14H21NO | 详情 | 详情 | |
| (V) | 14649 | (2S)-5-methoxy-N-propyl-1,2,3,4-tetrahydro-2-naphthalenamine; N-[(2S)-5-methoxy-1,2,3,4-tetrahydro-2-naphthalenyl]-N-propylamine | C14H21NO | 详情 | 详情 | |
| (VI) | 14650 | (6S)-6-(propylamino)-5,6,7,8-tetrahydro-1-naphthalenol | C13H19NO | 详情 | 详情 | |
| (VII) | 14651 | (6S)-6-[propyl[2-(2-thienyl)ethyl]amino]-5,6,7,8-tetrahydro-1-naphthalenol | C19H25NOS | 详情 | 详情 |