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【结 构 式】 
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【分子编号】18121 【品名】5-(4-nitrophenyl)-7,9-dihydro-8H-[1,3]dioxolo[4,5-h][2,3]benzodiazepin-8-one 【CA登记号】 |
【 分 子 式 】C16H11N3O5 【 分 子 量 】325.28056 【元素组成】C 59.08% H 3.41% N 12.92% O 24.59% |
合成路线1
该中间体在本合成路线中的序号：(V)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 |
合成路线2
该中间体在本合成路线中的序号：(IV)Benzophenone (III) was prepared by Friedel-Crafts acylation of methyl 3,4-methylenedioxyphenylacetate (I) with 4-nitrobenzoic acid (II). Subsequent cyclization of (III) with hydrazine gave rise to benzodiazepinone (IV). This was treated with methyl isocyanate in the presence of triethylamine to yield the corresponding urea (V). Finally, the nitro group of (V) was reduced to the title aniline by catalytic hydrogenation using Pd-C.
| 【1】 De Sarro, G.; Micale, N.; Baraldi, M.; De Sarro, A.; Pula, G.; De Micheli, C.; Zappala, M.; Grasso, S.; Synthesis and anticonvulsant activity of novel and potent 2,3-benzodiazepine AMPA/kainate receptor antagonists. J Med Chem 1999, 42, 21, 4414. |
| 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) | 18118 | methyl 2-(1,3-benzodioxol-5-yl)acetate | C10H10O4 | 详情 | 详情 | |
| (II) | 18119 | 4-nitrobenzoic acid; p-nitrobenzoic acid | 62-23-7 | C7H5NO4 | 详情 | 详情 |
| (III) | 18120 | methyl 2-[6-(4-nitrobenzoyl)-1,3-benzodioxol-5-yl]acetate | C17H13NO7 | 详情 | 详情 | |
| (IV) | 18121 | 5-(4-nitrophenyl)-7,9-dihydro-8H-[1,3]dioxolo[4,5-h][2,3]benzodiazepin-8-one | C16H11N3O5 | 详情 | 详情 | |
| (V) | 41984 | N-methyl-5-(4-nitrophenyl)-8-oxo-8,9-dihydro-7H-[1,3]dioxolo[4,5-h][2,3]benzodiazepine-7-carboxamide | C18H14N4O6 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(I)Condensation of benzodiazepinone (I) with methyl isocyanate provides the 3 (N-methylcarbamoyl) derivative (II). Reduction of the nitro group of (II) with concomitant diazepinone ring cleavage in the presence of SnCl2 in refluxing MeOH then furnishes the title compound.
| 【1】 Micale, N.; Zappalà, M.; Grasso, S.; et al.; Novel potent AMPA/kainate receptor antagonists: Synthesis and anticonvulsant activity of a series of 2-[(4-alkylsemicarbazono)-(4-amino- phenyl)methyl]-4,5-methylenedioxyphenylacetic acid alkyl esters. J Med Chem 2002, 45, 20, 4433. |