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【结 构 式】 
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【分子编号】16182 【品名】2-(1-benzothiophen-5-yl)oxirane 【CA登记号】 |
【 分 子 式 】C10H8OS 【 分 子 量 】176.23892 【元素组成】C 68.15% H 4.58% O 9.08% S 18.19% |
合成路线1
该中间体在本合成路线中的序号：(V)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 |