【结 构 式】 |
【药物名称】Zolpidem, SL-800750 【化学名称】N,N,6-Trimethyl-2-p-tolylimidazo[1,2-a]pyridine-3-acetamide 【CA登记号】82626-48-0 【 分 子 式 】C19H21N3O 【 分 子 量 】307.39872 |
【开发单位】Sanofi-synthélabo (Originator) 【药理作用】PSYCHOPHARMACOLOGIC DRUGS, Sedative/Hypnotics, Sleep Disorders, Treatment of |
合成路线1
4-Methyl-2'-bromoacetophenone (I) is condensed with 2-amino-5-methyl pyridine (II) to give 2-(4-methylphenyl)-6-methylimidazo[1,2-a]pyridine (III). Compound (III) is condensed with formaldehyde and dimethylamine in a Mannich reaction to give the 3-dimethyl aminomethyl derivative (IV), which is quaternized on the side chain nitrogen to afford the quaternary iodide (V). Displacement of trimethylamine from the quaternary salt (V) with cyanide ion leads to 2-(4-methylphenyl)-6-methylimidazo[1,2-a]pyridine-3-acetonitrile (VI). Acid hydrolysis of the nitrile then affords the corresponding acid (VII). Conversion of the acid to its acid chloride followed by condensation with dimethylamine then leads to zolpidem free base, which is converted to its L-(+)- tartrate (2:1) by treatment with L-(+)-tartaric acid.
【1】 George, P.; Kaplan, J.-P. (Sanofi-Synthelabo ); Imidazo[1,2-a] pyridine derivs. and their applicat. EP 0050563; US 4382938 . |
【2】 Prenez, A.; Sauvanet, J.P.; Thenot, J.P.; Friedmann, J.C.; Dimsdale, M.; Zivkovic, B.; Zolpidem Tartrate. Drugs Fut 1987, 12, 8, 777. |
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) | 12753 | 2-Bromo-1-(4-methylphenyl)-1-ethanone | 619-41-0 | C9H9BrO | 详情 | 详情 |
(II) | 12752 | 5-Methyl-2-pyridinylamine; 2-Amino-5-methylpyridine; 5-Methyl-2-pyridinamine; 6-Amino-beta-picoline; 6-Amino-3-picoline | 1603-41-4 | C6H8N2 | 详情 | 详情 |
(III) | 12754 | 6-Methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridine | C15H14N2 | 详情 | 详情 | |
(IV) | 28210 | N,N-dimethyl-N-[[6-methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridin-3-yl]methyl]amine | C18H21N3 | 详情 | 详情 | |
(V) | 28211 | N,N,N-trimethyl[6-methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridin-3-yl]methanaminium iodide | C19H24IN3 | 详情 | 详情 | |
(VI) | 28212 | 2-[6-methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridin-3-yl]acetonitrile | C17H15N3 | 详情 | 详情 | |
(VII) | 28213 | 2-[6-methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridin-3-yl]acetic acid | C17H16N2O2 | 详情 | 详情 |