|
【结 构 式】 
|
【药物名称】Vinconate, OM-853(HCl), OC-340, Brenal 【化学名称】(±)-3-Ethyl-2,3,a,4-tetrahydro-1H-indolo[3,2,1-de][1,5]naphthyridine-6-carboxylic acid methyl ester 【CA登记号】70704-03-9, 70704-04-0 (HCl) 【 分 子 式 】C18H20N2O2 【 分 子 量 】296.3723 |
【开发单位】OmniChem (Originator), Mitsubishi Pharma (Licensee) 【药理作用】Cerebrovascular Diseases, Treatment of, Ischemic Stroke, Treatment of, NEUROLOGIC DRUGS, Stroke, Treatment of |
合成路线1
The reaction of methyl-2-oxoglutarate (I) with triethyl orthoformate (A) by means of H2SO4 in refluxing methanol gives methyl 2,2-diethoxyglutarate (II), which is hydrolyzed partially with NaOH in water yielding methyl 2,2-diethoxy-4-carboxybutanoate (III). The reduction of (III) with NaBH4 and BF3 ethearate affords methyl 5-hydroxy-2-oxopentanoate (IV). The controlled oxidation of (IV) with pyridinium chlorochromate and sodium acetate in methylene chloride gives methyl 2,5-dioxopentanoate (V), which is condensed with N-ethyltryptamine (VI) by means of acetic acid in refluxing benzene yielding the tricyclic ketoester (VII). Finally, this compound cyclizes again spontaneously.
| 【1】 Hannart, J.A.A.J. (OmniChem); Indole derivatives and therapeutically acting drugs. BE 0870887; DE 2842418; FR 2404639; GB 2005267; JP 7988300; JP 8331352; US 4200638 . |
| 【2】 Castaner, J.; Serradell, M.N.; Vinconate. Drugs Fut 1984, 9, 4, 283. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 21304 | Triethyl orthoformate; 1-(Diethoxymethoxy)ethane; Diethoxymethyl ethyl ether | 122-51-0 | C7H16O3 | 详情 | 详情 |
| (I) | 30571 | dimethyl 2-oxopentanedioate | 13192-04-6 | C7H10O5 | 详情 | 详情 |
| (II) | 30572 | dimethyl 2,2-diethoxypentanedioate | C11H20O6 | 详情 | 详情 | |
| (III) | 30573 | 4,4-diethoxy-5-methoxy-5-oxopentanoic acid | C10H18O6 | 详情 | 详情 | |
| (IV) | 30574 | 5-methoxy-4,5-dioxopentanoic acid | C6H8O5 | 详情 | 详情 | |
| (V) | 30575 | methyl 2,5-dioxopentanoate | C6H8O4 | 详情 | 详情 | |
| (VI) | 30576 | N-ethyl-2-(1H-indol-3-yl)-1-ethanamine; N-ethyl-N-[2-(1H-indol-3-yl)ethyl]amine | C12H16N2 | 详情 | 详情 | |
| (VII) | 30577 | methyl 4-(2-ethyl-2,3,4,9-tetrahydro-1H-beta-carbolin-1-yl)-2-oxobutanoate | C18H22N2O3 | 详情 | 详情 |