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【结 构 式】 
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【分子编号】60851 【品名】5,5-dibromo-4-(3-chloro-4-fluoroanilino)-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one 【CA登记号】 |
【 分 子 式 】C12H6Br2ClFN4O 【 分 子 量 】436.4651032 【元素组成】C 33.02% H 1.39% Br 36.61% Cl 8.12% F 4.35% N 12.84% O 3.67% |
合成路线1
该中间体在本合成路线中的序号：(VII)Condensation of cyano ester (I) with formamidine in the presence of NaOEt afforded the pyrimidinone derivative (II). Acetal hydrolysis of (II) with concomitant intramolecular cyclization under acidic conditions produced the pyrrolopyrimidinone (III), which was further chlorinated to (IV) in refluxing POCl3. Displacement of the 4-chloro of (IV) with 3-chloro-4-fluoroaniline (V) in the presence of silver triflate in hot DMF afforded the anilino pyrrolopyrimidine (VI). Oxidation of (VI) using pyridinium bromide perbromide furnished the alpha,alpha-dibromo lactam (VII). Reductive debromination of (VII) by means of zinc dust in AcOH gave intermediate (VIII).
| 【1】 Wei, C.C.; Tang, P.C.; McMahon, G.; Sun, L.; Hirth, K.P.; Liang, C.; Cui, J. (Sugen, Inc.); 4-Substd. 7-aza-indolin-2-ones and their use as protein kinase inhibitors. EP 1244672; WO 0146196 . |
| 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) | 14789 | ethyl 2-cyano-4,4-diethoxybutanoate | C11H19NO4 | 详情 | 详情 | |
| (II) | 60644 | 2-[4-bromo-2-(2-fluorobenzoyl)anilino]-2-oxoethyl 4-methylbenzenesulfonate | C22H17BrFNO5S | 详情 | 详情 | |
| (III) | 60045 | 3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one | C6H5N3O | 详情 | 详情 | |
| (IV) | 60046 | 4-chloro-7H-pyrrolo[2,3-d]pyrimidine；6-Chloro-7-deazapurine；4-chloropyrrolo[2,3-d]pyrimidine；4-Chloro-1H-pyrrolo[2,3-d]pyrimidine | 3680-69-1 | C6H4ClN3 | 详情 | 详情 |
| (V) | 18688 | 3-Chloro-4-fluorophenylamine; 3-Chloro-4-fluoroaniline | 367-21-5 | C6H5ClFN | 详情 | 详情 |
| (VI) | 60850 | N-(3-chloro-4-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine; N-(3-chloro-4-fluorophenyl)-N-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amine | C12H8ClFN4 | 详情 | 详情 | |
| (VII) | 60851 | 5,5-dibromo-4-(3-chloro-4-fluoroanilino)-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one | C12H6Br2ClFN4O | 详情 | 详情 | |
| (VIII) | 60852 | 4-(3-chloro-4-fluoroanilino)-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one | C12H8ClFN4O | 详情 | 详情 |