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【结 构 式】 
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【分子编号】54682 【品名】N-(3-chloro-4-fluorophenyl)-6-(methylsulfanyl)pyrimido[5,4-d]pyrimidin-4-amine; N-(3-chloro-4-fluorophenyl)-N-[6-(methylsulfanyl)pyrimido[5,4-d]pyrimidin-4-yl]amine 【CA登记号】 |
【 分 子 式 】C13H9ClFN5S 【 分 子 量 】321.7652632 【元素组成】C 48.53% H 2.82% Cl 11.02% F 5.9% N 21.77% S 9.97% |
合成路线1
该中间体在本合成路线中的序号：(VI)The reaction of 5-bromo-2-(methylsulfanyl)pyrimidine-4-carboxylic acid (I) with ammonia and CuSO4 in water gives 5-amino-2-(methylsulfanyl)pyrimidine-4-carboxylic acid (II), which is cyclized with formamide or formamidine acetate by heating at 180 C to yield 4-hydroxy-6-(methylsulfanyl)pyrimido[5,4-d]pyrimidine (III). The reaction of (III) with refluxing SOCl2 affords the corresponding 4-chloro derivative (IV), which is condensed with 3-chloro-4-fluoroaniline (V) in hot dioxane to provide the secondary amine (VI). Alternatively, (VI) can also be obtained by direct condensation of the 4-hydroxy compound (III) with aniline (V) by means of HMDS and Ts-OH at 140 ?C. The oxidation of the sulfanyl group of (VI) with MCPBA in dichloromethane provides a mixture of the sulfinyl derivative (VII) and the sulfonyl derivative (VIII), which, without isolation, is finally condensed with 1-methylpiperidin-4-amine (IX) by means of DIEA in hot DMF to give the target pyrimido-pyrimidine-diamine.
| 【1】 Himmelsbach, F.; Dahmann, G.; von Rüden, T.; Metz, T. (Dr. Karl Thomae GmbH); Pyrimido[5,4-d]pyrimidines, medicaments containing these cpds., their use and process for their production. DE 19608588; EP 0888351; JP 2000506151; US 5821240; WO 9732880 . |
| 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) | 54678 | 5-bromo-2-(methylsulfanyl)-4-pyrimidinecarboxylic acid | C6H5BrN2O2S | 详情 | 详情 | |
| (II) | 54679 | 5-amino-2-(methylsulfanyl)-4-pyrimidinecarboxylic acid | C6H7N3O2S | 详情 | 详情 | |
| (III) | 54680 | 6-(methylsulfanyl)pyrimido[5,4-d]pyrimidin-4-ol | C7H6N4OS | 详情 | 详情 | |
| (IV) | 54681 | 8-chloro-2-(methylsulfanyl)pyrimido[5,4-d]pyrimidine; 8-chloropyrimido[5,4-d]pyrimidin-2-yl methyl sulfide | C7H5ClN4S | 详情 | 详情 | |
| (V) | 18688 | 3-Chloro-4-fluorophenylamine; 3-Chloro-4-fluoroaniline | 367-21-5 | C6H5ClFN | 详情 | 详情 |
| (VI) | 54682 | N-(3-chloro-4-fluorophenyl)-6-(methylsulfanyl)pyrimido[5,4-d]pyrimidin-4-amine; N-(3-chloro-4-fluorophenyl)-N-[6-(methylsulfanyl)pyrimido[5,4-d]pyrimidin-4-yl]amine | C13H9ClFN5S | 详情 | 详情 | |
| (VII) | 54683 | N-(3-chloro-4-fluorophenyl)-6-(methylsulfinyl)pyrimido[5,4-d]pyrimidin-4-amine; N-(3-chloro-4-fluorophenyl)-N-[6-(methylsulfinyl)pyrimido[5,4-d]pyrimidin-4-yl]amine | C13H9ClFN5OS | 详情 | 详情 | |
| (VIII) | 54684 | N-(3-chloro-4-fluorophenyl)-6-(methylsulfonyl)pyrimido[5,4-d]pyrimidin-4-amine; N-(3-chloro-4-fluorophenyl)-N-[6-(methylsulfonyl)pyrimido[5,4-d]pyrimidin-4-yl]amine | C13H9ClFN5O2S | 详情 | 详情 | |
| (IX) | 54685 | 1-methyl-4-piperidinamine; 1-methyl-4-piperidinylamine | C6H14N2 | 详情 | 详情 |