反应详情

Reflux a solution of 2-[1,4]diazepan-1-yl-1-(4,4,4-trifluoro-butyl)-1H-benzoimidazole dihydroiodide (0.65 g, 1.12 immol), methanesulfonic acid 2-{(S)-1-[1-(2-methoxy-5-tetrazol-1-yl-phenyl)-methanoyl]-3-phenyl-pyrrolidin-3-yl}-ethyl ester (0.50 g, 1.06 mmol, example 47.2), triethylamine (3.58 mmol) and acetonitrile (15 mL) for 20 hours. Cool and concentrate in vacuo. Dilute with dichloromethane (150 mL), wash the organic phase with NaHCO3 solution (3×30 mL), dry (Na2SO4) the organic phase, filter and evaporate. Purify the residue by flash chromatography (silica gel, 7×15 cm) eluting with 10% methanol/0.1% ammonium hydroxide solution in dichloromethane and concentrate the appropriate fractions to afford 0.79 g of the title compound as a cream colored foam, Rf=0.46 (silica gel, 1.0% methanol/0.1% ammonium hydroxide solution in dichloromethane). The compound may be converted to the dihydrochloride salt by methods well known in the art.

1. temperatureCool
2. concentrationconcentrate in vacuo
3. additionDilute with dichloromethane (150 mL)
4. washwash the organic phase with NaHCO3 solution (3×30 mL)
5. dry with materialdry (Na2SO4) the organic phase
6. filtrationfilter
7. customevaporate
8. customPurify the residue by flash chromatography (silica gel, 7×15 cm)
9. washeluting with 10% methanol/0.1% ammonium hydroxide solution in dichloromethane
10. concentrationconcentrate the appropriate fractions