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【结 构 式】 
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【分子编号】29076 【品名】6-(4-aminobutyl)-5-methyl-3-pyridinamine 【CA登记号】 |
【 分 子 式 】C10H17N3 【 分 子 量 】179.2652 【元素组成】C 67% H 9.56% N 23.44% |
合成路线1
该中间体在本合成路线中的序号：(VI)The condensation of diethyl 2-(2-cyanoethyl)malonate (I) with 2-chloro-3-methyl-5-nitropyridine (II) by means of NaH in refluxing THF gives 4-(3-methyl-5-nitropyrid-2-yl)-4,4-bis(ethoxycarbonyl)butyronitrile (III), which is decarboxylated with NaOH in ethanol water yielding 4-(3-methyl-5-nitropyrid-2-yl)butyronitrile (IV). The reduction of (IV) with H2 over Pd/C in ethanol affords 4-(5-amino-3-methylpyrid-2-yl)butyronitrile (V), which is reduced further with LiAlH4 in ether-THF giving 5-amino-2-(4-aminobutyl)-3-methylpyridine (VI). The Sandmeyer reaction of (VI) with NaNO2, HBr and Cu2Br2 yields 5-bromo-2-(4-aminobutyl)-3-methylpyridine (VII), which is finally condensed with 2-nitroamino-5-(6-methylpyrid-2-ylmethyl)-4-pyrimidone (VIII) in refluxing pyridine.
| 【1】 Sach, G.S. (SmithKline Beecham plc); Histamine H1-antagonists. DD 202291; EP 0068833; EP 0068834; JP 58008079; JP 61233616; JP 61233670; US 4444772; US 4486434; US 4535163; US 4584381 . |
| 【2】 Serradell, M.N.; Castaner, J.; SKF-93944. Drugs Fut 1985, 10, 3, 209. |
| 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) | 22941 | diethyl 2-(2-cyanoethyl)malonate | 17216-62-5 | C10H15NO4 | 详情 | 详情 |
| (II) | 29072 | 2-chloro-3-methyl-5-nitropyridine | C6H5ClN2O2 | 详情 | 详情 | |
| (III) | 29073 | Diethyl 2-(2-cyanoethyl)-2-(3-methyl-5-nitro-2-pyridinyl)malonate | C16H19N3O6 | 详情 | 详情 | |
| (IV) | 29074 | 4-(3-methyl-5-nitro-2-pyridinyl)butanenitrile | C10H11N3O2 | 详情 | 详情 | |
| (V) | 29075 | 4-(5-amino-3-methyl-2-pyridinyl)butanenitrile | C10H13N3 | 详情 | 详情 | |
| (VI) | 29076 | 6-(4-aminobutyl)-5-methyl-3-pyridinamine | C10H17N3 | 详情 | 详情 | |
| (VII) | 29077 | 4-(5-bromo-3-methyl-2-pyridinyl)-1-butanamine | C10H15BrN2 | 详情 | 详情 | |
| (VIII) | 22953 | 5-(6-Methylpyridin-3-ylmethyl)-2-(nitroamino)pyrimidin-4(1H)-one | C11H11N5O3 | 详情 | 详情 |