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【结 构 式】

【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%

与该中间体有关的原料药合成路线共 1 条

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
Extended Information