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【结 构 式】 
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【药物名称】EGIS-8332 【化学名称】(+)-7-Acetyl-5-(4-aminophenyl)-8-methyl-8,9-dihydro-7H-1,3-dioxolo[4,5-h][2,3]benzodiazepine-8-carbonitrile 【CA登记号】220725-87-1 (undefined isomer), 220725-88-2 (undefined isomer; HCl salt) 【 分 子 式 】C20H18N4O3 【 分 子 量 】362.39146 |
【开发单位】Egis (Originator), Servier (Codevelopment) 【药理作用】Antiepileptic Drugs, Cerebrovascular Diseases, Treatment of, NEUROLOGIC DRUGS, Stroke, Treatment of, AMPA Antagonists, Kainate Antagonists |
合成路线1
The cyclization of benzophenone (I) with hydrazine in isopropanol gives 8-methyl-5-(4-nitrophenyl)-9H-1,3-dioxolo[4,5-h][2,3]benzodiazepine (II), which is treated with KCN in AcOH at 70 C in a sealed tube to afford nitrile (III). Subsequent treatment of (III) with acetyl chloride gave the N-acetyl benzodiazepine (IV). Finally, the nitro group of (IV) was reduced to the target amine by transfer hydrogenation using hydrazine and Pd/C.
| 【1】 Andrási, F.; Balogh, T.; Botka, P.; Elekes, I.; Goldschmidt, K.; Hámori, T.; Korosi, J.; Láng, T.; Moravcsik, I.; Sineger, E.; Somogyi, G.; Zolyomi, G. (Egis Pharmaceuticals Ltd.); 5H-2,3-Benzodiazepine derivs., process for their preparation and pharmaceutical compsns. which contain them. FR 2566774; HU 191702 . |
| 【2】 8-Substd.-9H-1,3-dioxolo[4,5-h][2,3]benzodiazepine derivs., as AMPA/kainate receptor inhibitors. EP 1003749; WO 9907707 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 19273 | acetyl chloride | 75-36-5 | C2H3ClO | 详情 | 详情 | |
| (I) | 35397 | 1-[6-(4-nitrobenzoyl)-1,3-benzodioxol-5-yl]acetone | C17H13NO6 | 详情 | 详情 | |
| (II) | 29266 | 8-methyl-5-(4-nitrophenyl)-9H-[1,3]dioxolo[4,5-h][2,3]benzodiazepine | C17H13N3O4 | 详情 | 详情 | |
| (III) | 35398 | 8-methyl-5-(4-nitrophenyl)-8,9-dihydro-7H-[1,3]dioxolo[4,5-h][2,3]benzodiazepine-8-carbonitrile | C18H14N4O4 | 详情 | 详情 | |
| (IV) | 35399 | 7-acetyl-8-methyl-5-(4-nitrophenyl)-8,9-dihydro-7H-[1,3]dioxolo[4,5-h][2,3]benzodiazepine-8-carbonitrile | C20H16N4O5 | 详情 | 详情 |