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【结 构 式】

【分子编号】16187

【品名】(1R)-1-(1-benzothiophen-5-yl)-2-[2-(diethylamino)ethoxy]ethyl acetate

【CA登记号】

【 分 子 式 】C18H25NO3S

【 分 子 量 】335.46744

【元素组成】C 64.45% H 7.51% N 4.18% O 14.31% S 9.56%

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:(X)

1) The reaction of dimethyl sulfate (I) with dimethyl sulfide (II) by means of sodium methoxide in acetonitrile gives dimethyl (methylene)-lambda4-sulfane (III), which, without isolation, is condensed with benzo[b]thiophene-5-carbaldehyde (IV) in the same solvent to yield 2-(benzo[b]thiophen-5-yl)oxirane (V) (1). The reaction of (V) with 2-(dimethylamino)ethanol (VI) by means of potassium tert-butoxide in hot DMSO (1, 2), or hot DMF (3) affords (±)-1-(benzo[b]thiophen-5-yl)-2-[2-(diethylamino)ethoxy]ethanol (racemic T-588) (VII), which is submitted to optical resolution first by treatment with acetic anhydride in refluxing toluene to give the corresponding acetate (VIII), and then by reaction of (VIII) with D-dibenzoyltartaric acid (IX) in ethyl acetate/acetone/water followed by fractionated crystallization of the resulting salt to yield the D-dibenzoyltartrate salt of the (R)-isomer (X). Finally, (X) is deacetylated with sodium methoxide in methanol and salified with ethanolic hydrochloric acid.

1 Ono, S.; Yamafuji, T.; Chaki, H.; Todo, Y.; Maekawa, M.; Kitamura, K.; Kimura, T.; Nakada, Y.; Mozumi, K.; Narita, H.; A new cognition-enhancing agent, (R)-(-)-1-(benzo[b]thiophen-5-yl)-2-[2-(N,N-diethylamino)ethoxy]ethanol hydrochloride. Effects on memory impairment in rats generated by cerebral embolization and basal forebrain lesions. Biol Pharm Bull 1995, 18, 12, 1779-83.
2 Ono, S.; Yamafuji, T.; Chaki, H.; Morita, H.; Todo, Y.; Okada, N.; Maekawa, M.; Kitamura, K.; Tai, M.; Narita, H.; Studies on cognitive enhancing agents. III. Antiamnestic and antihypoxic activities of a series of 1-bicycloaryl-2-(omega-aminoalkoxy)ethanols. Chem Pharm Bull 1995, 43, 9, 1492-6.
3 Martel, A.M.; Prous, J.; Castaner, J.; T-588. Drugs Fut 1997, 22, 4, 386.
4 Ono, S.; Yamafuji, T.; Chaki, H.; Maekawa, M.; Todo, Y.; Narita, H. (Toyama Chemical Co., Ltd.); 1,2-Ethanediol deriv. and salt thereof, process for producing the same, and cerebral function-improving agent comprising them. EP 0383281; EP 0587193; EP 0587194; EP 0589484; FR 2643079; JP 1991047158; JP 1991197422; US 5280032; US 5472984; US 5612381; US 5658904 .
5 Ono, T.; Yamafuji, T.; Chaki, H.; Maekawa, M.; Fujido, Y.; Narita, H. (Toyama Chemical Co., Ltd.); 1,2-Ethanediol derivs. and their salts. JP 1992095070 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(II) 16179 Dimethyl sulfide; (Methylsulfanyl)methane 75-18-3 C2H6S 详情 详情
(III) 16180 Dimethyl(methylene)-lambda(4)-sulfane; Dimethylsulfonium-methylide C3H8S 详情 详情
(IV) 16181 1-benzothiophene-5-carbaldehyde C9H6OS 详情 详情
(V) 16182 2-(1-benzothiophen-5-yl)oxirane C10H8OS 详情 详情
(VI) 16183 Diethylaminoethanol; 2-(diethylamino)-1-ethanol 100-37-8 C6H15NO 详情 详情
(VII) 16184 1-(1-benzothiophen-5-yl)-2-[2-(diethylamino)ethoxy]-1-ethanol C16H23NO2S 详情 详情
(VIII) 16185 1-(1-benzothiophen-5-yl)-2-[2-(diethylamino)ethoxy]ethyl acetate C18H25NO3S 详情 详情
(IX) 16186 (2R,3R)-2,3-bis(benzoyloxy)butanedioic acid C18H14O8 详情 详情
(X) 16187 (1R)-1-(1-benzothiophen-5-yl)-2-[2-(diethylamino)ethoxy]ethyl acetate C18H25NO3S 详情 详情
Extended Information