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【结 构 式】 
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【药物名称】 【化学名称】5-(4-Aminophenyl)-8,9-dihydro-7H-1,3-dioxolo[4,5-h][2,3]benzodiazepin-8-one 【CA登记号】197368-49-3 【 分 子 式 】C16H13N3O3 【 分 子 量 】295.30031 |
【开发单位】Acea (Originator) 【药理作用】Antiepileptic Drugs, Cerebrovascular Diseases, Treatment of, Ischemic Stroke, Treatment of, NEUROLOGIC DRUGS, Stroke, Treatment of, AMPA Antagonists |
合成路线1
Esterification of 3,4-(methylenedioxy)phenylacetic acid (I) with methanol in the presence of sulfuric acid provided methyl ester (II). Fiedel Crafts acylation of (II) with 4-nitrobenzoic acid (III) under the action of P2O5 in refluxing dichloroethane yielded ketone (IV). This compound was refluxed with hydrazine hydrate in ethanol to afford benzodiazepinone (V). Finally, the nitro group was reduced by hydrogenation in acetic acid with Pd/C as the catalyst or with Raney-Ni and hydrazine to give the corresponding amine.
| 【1】 Wang, Y.; et al.; Synthesis of 7,8-(methylenedioxy)-1-phenyl-3,5-dihydro-4H-2,3-benzodiazepin-4-ones as novel and potent noncompetitive AMPA receptor antagonists. J Med Chem 1998, 41, 14, 2621. |
| 【2】 Xia, H.; Field, G.; Lan, N.C.; Wang, Y. (Acea Pharmaceuticals); Substd. 2,3-benzodiazepin-4-ones and the use thereof. EP 1021418; JP 2000506890; US 5891871; WO 9734878 . |
| 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) | 18117 | 2-(1,3-benzodioxol-5-yl)acetic acid; 3,4-(Methylenedioxy)phenylacetic acid | 2861-28-1 | C9H8O4 | 详情 | 详情 |
| (II) | 18118 | methyl 2-(1,3-benzodioxol-5-yl)acetate | C10H10O4 | 详情 | 详情 | |
| (III) | 18119 | 4-nitrobenzoic acid; p-nitrobenzoic acid | 62-23-7 | C7H5NO4 | 详情 | 详情 |
| (IV) | 18120 | methyl 2-[6-(4-nitrobenzoyl)-1,3-benzodioxol-5-yl]acetate | C17H13NO7 | 详情 | 详情 | |
| (V) | 18121 | 5-(4-nitrophenyl)-7,9-dihydro-8H-[1,3]dioxolo[4,5-h][2,3]benzodiazepin-8-one | C16H11N3O5 | 详情 | 详情 |