【结 构 式】 |
【药物名称】E-3620 【化学名称】(-)-4-Amino-5-chloro-N-(endo-8-methyl-8-azabicyclo[3.2.1]oct-3alpha-yl)-2-[1(S)-methyl-2-butynyloxy]benzamide monohydrochloride 【CA登记号】 【 分 子 式 】C20H27Cl2N3O2 【 分 子 量 】412.36309 |
【开发单位】Eisai (Originator) 【药理作用】Agents for Gastritis, Gastric Emptying Disorders,Treatment of of, GASTROINTESTINAL DRUGS, Irritable Bowel Syndrome, Agents for, 5-HT3 Antagonists, 5-HT4 Agonists |
合成路线1
Coupling of methyl 4-acetamido-5-chlorosalicylate (I) with 3-penty-2-ol (II) under Mitsunobu conditions furnished the propargyl ether (III). Acetamide hydrolysis en (III) using H2SO in methanol gave aminoester (IV), whih was further hydrolyzed with NaOH to the carboxylic acid (V). Condensation of racemic acid (V) with the aminopropane (VI) in the presence of DCC afforded the corresponding amide, which was resolved into the enantiomers by means of preparative, chiral HPLC.
【1】 Miyazawa, S.; Hibi, S.; Yoshimura, H.; Mori, T.; Hoshino, Y.; Nagai, M.; Kikuchi, K.; Shibata, H.; Hirota, K.; Yamanaka, T.; Yamatsu, I.; Mizuno, M. (Eisai Co., Ltd.); Aminobenzoic acid derivs.. EP 0554794; JP 1994128254; JP 1998007674; US 5389643; US 5578603 . |
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) | 59800 | methyl 4-(acetylamino)-5-chloro-2-hydroxybenzoate | C10H10ClNO4 | 详情 | 详情 | |
(II) | 59801 | 3-pentyn-2-ol | C5H8O | 详情 | 详情 | |
(III) | 59802 | methyl 4-(acetylamino)-5-chloro-2-[(1-methyl-2-butynyl)oxy]benzoate | C15H16ClNO4 | 详情 | 详情 | |
(IV) | 59803 | methyl 4-amino-5-chloro-2-[(1-methyl-2-butynyl)oxy]benzoate | C13H14ClNO3 | 详情 | 详情 | |
(V) | 59804 | 4-amino-5-chloro-2-[(1-methyl-2-butynyl)oxy]benzoic acid | C12H12ClNO3 | 详情 | 详情 | |
(VI) | 12412 | (1R,5S)-8-Methyl-8-azabicyclo[3.2.1]octan-3-amine; (1R,5S)-8-Methyl-8-azabicyclo[3.2.1]oct-3-ylamine | C8H16N2 | 详情 | 详情 |