【结 构 式】 |
【药物名称】Alpidem, SL-80.0342-00, Ananxyl 【化学名称】6-Chloro-2-(4-chlorophenyl)-N,N-dipropylimidazo[1,2-a]pyridine-3-acetamide 【CA登记号】82626-01-5 【 分 子 式 】C21H23Cl2N3O 【 分 子 量 】404.34296 |
【开发单位】Sanofi-synthélabo (Originator), Lorex (Licensee) 【药理作用】Anxiolytics, PSYCHOPHARMACOLOGIC DRUGS |
合成路线1
1) 4-Chloro-2'-bromoacetophenone (I) is condensed with 2-amino 5-chloropyridine (II) to give 6-chloro-2-(4-chlorophenyl)imidazo[1,2-a]pyridine (III). 2) The above compound is reacted with formaldehyde and dimethylamine under Mannich conditions affording the 3-dimethylaminomethyl derivative (IV), which is subsequently quaternized with methyl iodide to afford the quaternary iodide (V). 3) Displacement of trimethylamine from salt (V) with cyanide ion leads to formation of the nitrile (VI), which on hydrolysis with hydrochloric acid in acetic acid gives the corresponding acid (VII). 4) In situ conversion of the acid to its acid chloride with phosphorus oxychloride followed by treatment with di-n-propylamine then leads to alpidem.
【1】 George, P.; Kaplan, J.-P. (Sanofi-Synthelabo ); Imidazo[1,2-a] pyridine derivs. and their applicat. EP 0050563; US 4382938 . |
【2】 Friedmann, J.C.; Morselli, P.L.; Dimsdale, M.; Zivkovic, B.; Alpidem. Drugs Fut 1988, 13, 2, 106. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(2) | 21856 | N,N-dipropylamine; N-propyl-1-propanamine | 142-84-7 | C6H15N | 详情 | 详情 |
(I) | 16720 | 2-bromo-1-(4-chlorophenyl)-1-ethanone; 2-Bromo-4'-chloroacetophenone | 536-38-9 | C8H6BrClO | 详情 | 详情 |
(II) | 18559 | 5-Chloro-2-pyridinylamine; 5-Chloro-2-pyridinamine; 2-Amino-5-chloropyridine | 1072-98-6 | C5H5ClN2 | 详情 | 详情 |
(III) | 21851 | 6-chloro-2-(4-chlorophenyl)imidazo[1,2-a]pyridine | C13H8Cl2N2 | 详情 | 详情 | |
(IV) | 21852 | [6-chloro-2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl]-N,N-dimethylmethanamine; N-[[6-chloro-2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl]methyl]-N,N-dimethylamine | C16H15Cl2N3 | 详情 | 详情 | |
(V) | 21853 | [6-chloro-2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl]-N,N,N-trimethylmethanaminium iodide | C17H18Cl2IN3 | 详情 | 详情 | |
(VI) | 21854 | 2-[6-chloro-2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl]acetonitrile | C15H9Cl2N3 | 详情 | 详情 | |
(VII) | 21855 | 2-[6-chloro-2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl]acetic acid | C15H10Cl2N2O2 | 详情 | 详情 |