反应详情

温度

0 °C

Treat a stirred solution of 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 (0.25 g, 0.22 mmol) and dichloromethane (5 mL) at 0° C. with diisopropylethylamine (0.14 mL, 0.84 mmol) and methane sulfonyl chloride (0.04 mL, 0.5 mmol). Stir the reaction mixture at 0° C. for two hours, dilute with dichloromethane and wash with water. Dry (MgSO4) the organic phase, filter and concentrate the filtrate in vacuo. Purify the product by column chromatography (silica gel, elute sequentially with 3% methanol in dichloromethane then with 5% methanol in dichloromethane) and concentrate the appropriate fractions to afford 0.19 g of the title compound, Rf=0.28 (silica gel, 5% methanol in dichloromethane). The compound may be converted to the dihydrochloride salt by methods swell known in the art.

1. washwash with water
2. dry with materialDry (MgSO4) the organic phase
3. filtrationfilter
4. concentrationconcentrate the filtrate in vacuo
5. customPurify the product by column chromatography (silica gel
6. washelute sequentially with 3% methanol in dichloromethane
7. concentrationwith 5% methanol in dichloromethane) and concentrate the appropriate fractions