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【结 构 式】 
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【药物名称】Flupirtine maleate, D-9998, Katadolon 【化学名称】2-Amino-3-carbethoxyamino-6-(p-fluorobenzylamino)pyridine maleate 【CA登记号】75507-68-5, 56995-20-1 (free base) 【 分 子 式 】C19H21FN4O6 【 分 子 量 】420.40082 |
【开发单位】Asta Medica (Originator), AWD.pharma (Licensee), Lindopharm (Licensee) 【药理作用】ANALGESIC AND ANESTHETIC DRUGS, Analgesic Drugs, Creutzfeldt-Jakob Disease, Treatment of, Neurodegenerative Diseases, Treatment of, NEUROLOGIC DRUGS, Non-Opioid Analgesics, Prion Diseases, Treatment of, Voltage-Gated KCNQ Channel Activators |
合成路线1
The reaction of 2,6-dichloro-3-nitropyridine (I) with ammonia yields 2-amino-3-nitro-chloropyridine (II). 4-Fluorobenzylamine (III) reacts in dioxane and in the presence of triethylamine with (II), resulting in the 2-amino-3-nitro-6-p-fluorobenzylamine derivative (IV). The latter is hydrated and in situ the 3-amino group is condensed with ethyl chloroformate leading to the stable 2-amino-3-carbethoxyamino-6-(p-fluorobenzylamino)pyridine (Flupirtine).
| 【1】 Thiele, K.; Steinmetz, G.; Bebenburg, W.v.; Chem Ztg 1979, 103, 10, 387. |
| 【2】 Bebenburg, W.v.; Engel, J.; Sheldrick, W.S.; Thiele, K.; Chem Ztg 1981, 105, 10, 217. |
| 【3】 Castaner, J.; Serradell, M.N.; Blancafort, P.; Flupirtine. Drugs Fut 1983, 8, 9, 773. |
| 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) | 13574 | 2,6-Dichloro-3-nitropyridine | 16013-85-7 | C5H2Cl2N2O2 | 详情 | 详情 |
| (II) | 13575 | 6-Chloro-3-nitro-2-pyridinamine; 2-Amino-6-chloro-3-nitropyridine; 6-Chloro-3-nitro-2-pyridinylamine | 27048-04-0 | C5H4ClN3O2 | 详情 | 详情 |
| (III) | 31095 | 4-fluorobenzylamine; (4-fluorophenyl)methanamine | 140-75-0 | C7H8FN | 详情 | 详情 |
| (IV) | 13576 | N(6)-(4-Fluorobenzyl)-3-nitro-2,6-pyridinediamine; N-(6-Amino-5-nitro-2-pyridinyl)-N-(4-fluorobenzyl)amine | C12H11FN4O2 | 详情 | 详情 | |
| (V) | 13577 | N(6)-(4-Fluorobenzyl)-2,3,6-pyridinetriamine; 2-Amino-6-[(4-fluorobenzyl)amino]-3-pyridinylamine | C12H13FN4 | 详情 | 详情 |