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【结 构 式】 
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【分子编号】62310 【品名】Methyl 3-nitro-o-toluate; 2-Methyl-3-nitrobenzoic acid 【CA登记号】59382-59-1 |
【 分 子 式 】C9H9NO4 【 分 子 量 】195.1748 【元素组成】C 55.39% H 4.65% N 7.18% O 32.79% |
合成路线1
该中间体在本合成路线中的序号：(IV)Cyclization of N-(benzyloxycarbonyl)glutamine (I) by means of CDI in refluxing THF gives 3-(benzyloxycarbonylamino)piperidine-2,6-dione (II), which is deprotected with H2 over Pd/C in ethyl acetate/4N HCl to yield 3-aminopiperidine-2,6-dione hydrochloride (III). Bromination of 2-methyl-3-nitrobenzoic acid methyl ester (IV) with NBS in CCl4 provides 2-(bromomethyl)-3-nitrobenzoic acid methyl ester (V), which is cyclized with the aminopiperidine (III) by means of triethylamine in hot DMF to afford 3-(4-nitro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (VI). Finally, the nitro group of compound (VI) is reduced with H2 over Pd/C in methanol (1, 2).
| 【1】 Sorbera, L.A.; Castaner, J.; Bayes, M.; CC-5013. Drugs Fut 2003, 28, 5, 425. |
| 【2】 Muller, G.W.; Huang, S.-Y.; Chen, R.; et al.; Amino-substituted thalidomide analogs: Potent inhibitors of TNF-alpha production. Bioorg Med Chem Lett 1999, 9, 11, 1625. |
| 【3】 Stirling, D.I.; Muller, G.W.; Chen, R.S.-C. (Celgene Corp.); Substd. 2-(2,6-dioxopiperidin-3-yl)-phthalimides and -1-oxoisoindolines and method of reducing TNFalpha levels. EP 0925294; US 5635517; WO 9803502 . |
| 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) | 37578 | N(2)-[(benzyloxy)carbonyl]glutamine | C13H16N2O5 | 详情 | 详情 | |
| (II) | 37575 | benzyl 2,6-dioxo-3-piperidinylcarbamate | C13H14N2O4 | 详情 | 详情 | |
| (III) | 37576 | 3-amino-2,6-piperidinedione；3-aminopiperidine-2,6-dione；2-amino-Glutarimide；Glutamimide;a-Aminoglutarimide | 2353-44-8 | C5H8N2O2 | 详情 | 详情 |
| (IV) | 62310 | Methyl 3-nitro-o-toluate; 2-Methyl-3-nitrobenzoic acid | 59382-59-1 | C9H9NO4 | 详情 | 详情 |
| (V) | 62309 | methyl 2-(bromomethyl)-3-nitrobenzoate | 98475-07-1 | C9H8BrNO4 | 详情 | 详情 |
| (VI) | 62311 | 3-(4-nitro-1-oxo-1,3-dihydro-2H-isoindol-2-yl)-2,6-piperidinedione | C13H11N3O5 | 详情 | 详情 |