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【结 构 式】 
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【分子编号】24837 【品名】dimethyl 5-(4-methoxybenzoyl)-2,3-dihydro-1H-pyrrolizine-1,1-dicarboxylate 【CA登记号】 |
【 分 子 式 】C19H19NO6 【 分 子 量 】357.363 【元素组成】C 63.86% H 5.36% N 3.92% O 26.86% |
合成路线1
该中间体在本合成路线中的序号：(VIII)This compound can be obtained in the following way: 1) The reaction of N,N-dimethyl 4-methoxybenzamide (I) with 2-(methylthio)pyrrole) (II) by means of POCl3 in refluxing dichloromethane gives 5-(4-methoxyhenzoyl)-2-(methylthio)pyrrole (III), which is oxidized with m-chloroperbenzoic acid in dichloromethane to the corresponding sulfone (IV). The condensation of (IV) with 5,5-dimethylene-2,2-dimethyl-1,3-dioxane-4,6-dione (V) by means of NaH in hot DMF affords the intermediate compound (VI), which by methanolysis with methanol and HCl is converted to 5-(4 methoxybenzoy)-1-[3,3-di-(methoxycarbonyl)propyl]-2-(methylsulfonyl)pyrrole (VII). The cyclization of (VII) by means of NaH in hot DMF gives dimethyl-5-(4-methoxybenzoyl)-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1,1-dicarboxylate (VIII), which is finally hydrolyzed and decarboxylated with KOH in refluxing methanol-water.
| 【1】 Greenhouse, R.; Franco, F.; Novel syntheses of 5-aroyl-1,2-dihydro-3H-pyrrole-1-carboxilic acids. J Org Chem 1982, 47, 1682. |
| 【2】 Engler, H.; Schickaneder, H.; Szelenyi, I. (Heumann Pharma GmbH & Co.); Imidazoyl-substd. thiomethylpyridine derivs., method of administration thereof and medicaments containing them. DE 3216843; EP 0093252; US 4810715 . |
| 【3】 Muchowski, J.M.; Greenhouse, R. (Roche Bioscience); Process for preparing 5-aroyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acids and novel intermediates therein. US 4347186 . |
| 【4】 Prous, J.; Castaner, J.; Anirolac. Drugs Fut 1986, 11, 6, 449. |
| 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) | 24830 | 4-methoxy-N,N-dimethylbenzamide | C10H13NO2 | 详情 | 详情 | |
| (II) | 24831 | 2-(methylsulfanyl)-1H-pyrrole | C5H7NS | 详情 | 详情 | |
| (III) | 24832 | (4-methoxyphenyl)[5-(methylsulfanyl)-1H-pyrrol-2-yl]methanone | C13H13NO2S | 详情 | 详情 | |
| (IV) | 24833 | (4-methoxyphenyl)[5-(methylsulfonyl)-1H-pyrrol-2-yl]methanone | C13H13NO4S | 详情 | 详情 | |
| (V) | 11639 | 6,6-Dimethyl-5,7-dioxaspiro[2.5]octane-4,8-dione | 5617-70-9 | C8H10O4 | 详情 | 详情 |
| (VI) | 24835 | 5-[2-[2-(4-methoxybenzoyl)-5-(methylsulfonyl)-1H-pyrrol-1-yl]ethyl]-2,2-dimethyl-1,3-dioxane-4,6-dione | C21H23NO8S | 详情 | 详情 | |
| (VII) | 24836 | dimethyl 2-[2-[2-(4-methoxybenzoyl)-5-(methylsulfonyl)-1H-pyrrol-1-yl]ethyl]malonate | C20H23NO8S | 详情 | 详情 | |
| (VIII) | 24837 | dimethyl 5-(4-methoxybenzoyl)-2,3-dihydro-1H-pyrrolizine-1,1-dicarboxylate | C19H19NO6 | 详情 | 详情 | |
| (XI) | 24838 | 5-[2-[2-(4-methoxybenzoyl)-5-(methylsulfanyl)-1H-pyrrol-1-yl]ethyl]-2,2-dimethyl-1,3-dioxane-4,6-dione | C21H23NO6S | 详情 | 详情 |