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【结 构 式】 
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【药物名称】 【化学名称】3-(2-Bromo-4-isopropylphenyl)-7-(N-butyl-N-ethylamino)-1,5-dimethyl-2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-one 【CA登记号】 【 分 子 式 】C23H31BrN4O 【 分 子 量 】459.43372 |
【开发单位】Bristol-Myers Squibb (Originator) 【药理作用】Antidepressants, Anxiolytics, Mood Disorders, Treatment of, PSYCHOPHARMACOLOGIC DRUGS, CRF1 Antagonists |
合成路线1
4-Hydroxy-6-methyl-3-nitro-2-pyridone (I) was treated with phosphoryl chloride in boiling N,N-diethylaniline, and the resulting dichloropyridine (II) was condensed with n-butyl ethylamine (III) to afford a regioisomeric mixture of 4- (IV) and 2-amino (V) pyridines. After chromatographic separation, the desired isomer (IV) was coupled with 2-bromo-4-isopropylaniline (VI) at 140 C to provide (VII). Reduction of the nitro group of (VII) using sodium hydrosulfite and ammonia yielded diamine (VIII). Subsequent cyclization of (VIII) with phosgene in refluxing toluene gave imidazopyridinone (IX), which was finally N-methylated by means of CH3I and KOH in acetone.
| 【1】 Beck, J.P.; et al.; Purin-8-ones as corticotropin-releasing hormone (CRH-R1) receptor antagonists. Bioorg Med Chem Lett 1999, 9, 7, 967. |
| 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) | 23337 | 4-hydroxy-6-methyl-3-nitro-2(1H)-pyridinone | 4966-90-9 | C6H6N2O4 | 详情 | 详情 |
| (II) | 26787 | 2,4-dichloro-6-methyl-3-nitropyridine | C6H4Cl2N2O2 | 详情 | 详情 | |
| (III) | 26788 | N-butyl-N-ethylamine | 13360-63-9 | C6H15N | 详情 | 详情 |
| (IV) | 26789 | N-butyl-2-chloro-N-ethyl-6-methyl-3-nitro-4-pyridinamine | C12H18ClN3O2 | 详情 | 详情 | |
| (V) | 26790 | N-butyl-4-chloro-N-ethyl-6-methyl-3-nitro-2-pyridinamine | C12H18ClN3O2 | 详情 | 详情 | |
| (VI) | 23782 | 2-bromo-4-isopropylaniline; 2-bromo-4-isopropylphenylamine | 51605-97-1 | C9H12BrN | 详情 | 详情 |
| (VII) | 26791 | N-[2-(2-bromo-4-isopropylanilino)-6-methyl-3-nitro-4-pyridinyl]-N-butyl-N-ethylamine | C21H29BrN4O2 | 详情 | 详情 | |
| (VIII) | 26792 | N-[3-amino-2-(2-bromo-4-isopropylanilino)-6-methyl-4-pyridinyl]-N-butyl-N-ethylamine | C21H31BrN4 | 详情 | 详情 | |
| (IX) | 26793 | 3-(2-bromo-4-isopropylphenyl)-7-[butyl(ethyl)amino]-5-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one | C22H29BrN4O | 详情 | 详情 |