Acetonitrile → 1-((R)-3-{2-[4-(1-Cyclopropylmethyl-1H-benzoimidazol-2-yl)-[1,4]diazepan-1-yl]-ethyl}-3-phenyl-pyrrolidin-1-yl)-1-(2-methoxy-5-tetrazol-1-yl-phenyl)-methanone

Participants

Reaction Steps

Reflux a mixture of 1-cyclopropylmethyl-2-[1,4]diazepan-1-yl-1H-benzoimidazole dihydroiodide (0.60 g, 1.14 mmol), methanesulfonic acid 2-{(S)-1-[1-(2-methoxy-5-tetrazol-1-yl-phenyl)-methanoyl]-3-phenyl-pyrrolidin-3-yl}-ethyl ester (0.53 g, 1.12 mmol, example 47.2), triethylamine (0.65 mL, 4.66 mmol) and acetonitrile (10 mL) for 8 hours. Cool and dilute with dichloromethane (150 mL), wash the organic phase with NaHCO3 (30 mL) and saturated brine solution (30 mL), dry (MgSO4) the organic phase, filter and evaporate. Purify the residue by silica gel chromatography (4×41 cm) eluting with dichloromethane:methanol:30% ammonium hydroxide (95:5:0.05} to afford 0.47 g of the title compound, Rf=0.32 (silica gel, dichloromethane:methanol:30% ammonium hydroxide solution. The compound may be converted to the dihydrochloride salt by methods well known in the art.

Provenance & Evidence