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【结 构 式】 
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【药物名称】Gacyclidine, GK-11 【化学名称】cis-1-[2-Methyl-1-(2-thienyl)cyclohexyl]piperidine 【CA登记号】68134-81-6 【 分 子 式 】C16H25NS 【 分 子 量 】263.44835 |
【开发单位】CNRS (Originator), INSERM (Originator), Ipsen (Originator) 【药理作用】Cerebrovascular Diseases, Treatment of, Ischemic Stroke, Treatment of, NEUROLOGIC DRUGS, Stroke, Treatment of, NMDA Antagonists |
合成路线1
The condensation of 2-methylcyclohexanone (I) with 2-thienyl lithium (II) or 2-thienylmagnesium bromide (III) gives cyclohexanol (IV) as a diastereomeric mixture, which was treated with Na-N3 in trichloroacetic acid to yield the azide (V). The reduction of (V) with LiAlH4 or RaNi/iPr-OH affords the corresponding amine (VI), preferentially with the cis-configuration. Finally, this compound is condensed with 1,5-dibromopentane (VII) by means of K2CO3 in acetonitrile to provide the target compound as a diastereomeric mixture. The separation of the cis- and trans- racemates has been performed by HPLC. The optical resolution was performed by a cumbersome crystallization process using CSA and di-p-toluoyltartaric acid.
| 【1】 Michaud, M.; et al.; Homochiral structures derived from 1-[1-(2-thienyl)cyclohexyl]piperidine (TCP) are potent non-competitive antagonists of glutamate at NMDA receptor sites. Eur J Med Chem 1994, 29, 11, 869. |
| 【2】 Kamenka, J.-M.; Privat, A.; Chicheportiche, R.; Rondouin, G. (CNRS (Centre National de la Recherche Scientifique)); Pharmaceutical compsns. for neuroprotection containing arylcyclohexylamines. US 5179109; WO 9005524 . |
| 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) | 54406 | 2-Methylcyclohexanone; Tetrahydro-o-cresol; o-Methylcyclohexanone | 583-60-8 | C7H12O | 详情 | 详情 |
| (II) | 21682 | 2-thienyllithium | 2786-07-4 | C4H3LiS | 详情 | 详情 |
| (III) | 32082 | bromo(2-thienyl)magnesium | 5713-61-1 | C4H3BrMgS | 详情 | 详情 |
| (IV) | 54407 | (1R,2S)-2-methyl-1-(2-thienyl)cyclohexanol | C11H16OS | 详情 | 详情 | |
| (V) | 54408 | (1R,2S)-2-methyl-1-(2-thienyl)cyclohexyl azide; 2-[(1R,2S)-1-azido-2-methylcyclohexyl]thiophene | C11H15N3S | 详情 | 详情 | |
| (VI) | 54409 | (1R,2S)-2-methyl-1-(2-thienyl)cyclohexanamine; (1R,2S)-2-methyl-1-(2-thienyl)cyclohexylamine | C11H17NS | 详情 | 详情 | |
| (VII) | 30560 | 1,5-dibromopentane | 111-24-0 | C5H10Br2 | 详情 | 详情 |