反应详情

Reflux a stirred solution of 2-[1,4]diazepan-1-yl-1-(2,2,2-trifluoro-ethyl)-1H-benzoimidazole dihydroiodide (0.44 g, 0.79 mmol), methanesulfonic acid 2-{(S)-1-[1-(2-methoxy-5-tetrazol-1-yl-phenyl)-methanoyl]-3-phenyl-pyrrolidin-3-yl}-ethyl ester (0.38 g, 0.79 mmol, example 47.2), triethylamine (2.54 mmol) and acetonitrile (11 mL) under argon for 20 hours. Cool and concentrate in vacuo. Dilute with dichloromethane (100 mL), wash the organic phase with NaHCO3 solution (2×20 mL), dry (Na2SO4) the organic phase, filter and evaporate in vacuo. Purify the residue by flash chromatography (silica gel, 7×15 cm) eluting with 10% methanol/0.1% ammonium hydroxide solution in dichloromethane, concentrate the appropriate fractions, and dry the resultant material in vacuo (0.2 Torr) for 2 hours to afford 0.41 g of the title compound as a beige colored foam, Rf=0.39 (silica gel, 10% 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 (100 mL)
4. washwash the organic phase with NaHCO3 solution (2×20 mL)
5. dry with materialdry (Na2SO4) the organic phase
6. filtrationfilter
7. customevaporate in vacuo
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
11. dry with materialdry the resultant material in vacuo (0.2 Torr) for 2 hours