反应详情

Stir a mixture of 1-(2-ethoxy-ethyl)-2-{4-[2-((S)-3-phenyl-pyrrolidin-3-yl)-ethyl]-[1,4]diazepan-1-yl}-1H-benzoimidazole dihydrochloride (0.53 g, 1 mmol, Preparation 12.1, named as 3-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl) [1,4]diazepan-1-yl)ethyl)-3-phenylpyrrolidine), 4-hydroxy-2-methoxybenzoic acid (0.34 g), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (0.19 g, 1 mmol, Aldrich Chemical Company), 1-hydroxybenzotriazole hydrate (0.14 g, 1 mmol, Aldrich Chemical Company), diisopropyoethylamine (3.4 mL) and dichloromethane (10 mL) overnight at room temperature. Dilute the reaction mixture with dichloromethane, wash with saturated brine, dry (MgSO4) the organic phase, filter and concentrate the filtrate in vacuo. Purify the residue by column chromatography on silica gel eluting sequentially with ethyl acetate, 3% methanol in dichloromethane and 10% methanol in dichloromethane. Concentrate the appropriate fractions to afford 1-[(R)-3-(2-{4-[1-(2-ethoxy-ethyl)-1H-benzoimidazol-2-yl]-[1,4]diazepan-1-yl}-ethyl)-3-phenyl-pyrrolidin-1-yl]-1-(5-hydroxy-2-methoxy-phenyl)-methanone (0.19 g), Rf=0.38 (silica gel, 10% methanol in dichloromethane).

1. washwash with saturated brine
2. dry with materialdry (MgSO4) the organic phase
3. filtrationfilter
4. concentrationconcentrate the filtrate in vacuo
5. customPurify the residue by column chromatography on silica gel eluting sequentially with ethyl acetate, 3% methanol in dichloromethane and 10% methanol in dichloromethane
6. concentrationConcentrate the appropriate fractions