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【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
Extended Information