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【结 构 式】 
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【药物名称】D-19274 【化学名称】3-[2-Amino-6-(4-fluorobenzylamino)pyridin-3-yl]oxazolidin-2-one hydrochloride 【CA登记号】157840-43-2 【 分 子 式 】C15H16ClFN4O2 【 分 子 量 】338.77177 |
【开发单位】Asta Medica (Originator) 【药理作用】Antiepileptic Drugs, NEUROLOGIC DRUGS |
合成路线1
D-19274 can be obtained in a 6-step synthesis starting from 2,6-dichloropyridine (I). Compound (I) is nitrated with HNO3/H2SO4 yielding 2,6-dichloro-3-nitropyridine (II). Subsequent reaction with ammonia and 4-fluorobenzylamine leads to 2-amino-3-nitro-6-(4-fluorobenzylamino)pyridine (IV), which is hydrogenated using Raney Nickel as catalyst to the corresponding 3-amino derivative (V), which reacts with 2-bromoethyl chloroformate to 2-bromoethyl [N-(2-amino-6-(4-fluorobenzylamino)pyridin-3-yl)]carbamate hydrochloride (VI). (VI) is then treated with excess NaOH at 35 C, followed by treatment with isopropanol HCl to give the desired D-19274.
| 【1】 Engel, J.; Emig, P.; Nickel, B.; Szelenyi, I. (Asta Medica AG); 3-(N-heterocyclyl)-2,6-diaminopyridines and N-oxides, their preparation and their use as medicines. DE 3915184; EP 0343429; JP 1990017186; US 4923858 . |
| 【2】 Emig, P.; Engel, J.; Nickel, B.; Szelenyi, I.; Werner, U.; D-19274. Drugs Fut 1990, 15, 3, 223. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 31095 | 4-fluorobenzylamine; (4-fluorophenyl)methanamine | 140-75-0 | C7H8FN | 详情 | 详情 | |
| 63775 | 1-bromo-2-[(chlorocarbonyl)oxy]ethane | C3H4BrClO2 | 详情 | 详情 | ||
| (I) | 13573 | 2,6-Dichloropyridine | 2402-78-0 | C5H3Cl2N | 详情 | 详情 |
| (II) | 13574 | 2,6-Dichloro-3-nitropyridine | 16013-85-7 | C5H2Cl2N2O2 | 详情 | 详情 |
| (III) | 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 |
| (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 | |
| (VI) | 13578 | 2-bromoethyl 2-amino-6-[(4-fluorobenzyl)amino]-3-pyridinylcarbamate | C15H16BrFN4O2 | 详情 | 详情 |