反应详情

温度

81 °C

Heat at 81° C. a mixture of 1-(2-cyclopropylmethoxy-ethyl)-2-[1,4]diazepan-1-yl-1H-benzoimidazole (0.10 g, 0.33 mmol) and methanesulfonic acid 2-{(S)-1-[1-(2-methoxy-5-tetrazol-1-yl-phenyl)-methanoyl]-3-phenyl-pyrrolidin-3-yl}-ethyl ester (0.60 g, 1.27 mmol, example 47.2), triethylamine (0.136 mL, 3 equivalents), sodium iodide (0.097 g, 2 equivalents) and acetonitrile (8.1 mL) under argon for 30 hours. Quench the reaction as described in Example 113. Purify the crude material by column chromatography (silica gel, 4.5 cm×15 cm, using step gradient elution with 0%, 5% and 10% methanol in dichloromethane. Concentrate the appropriate fractions to afford 0.16 g of the title compound, Rf=0.33 (silica gel, 10% methanol in dichloromethane). The compound may be converted to the dihydrochloride salt, m.p. 135-155° C. (dec.), by methods well known in the art.

1. customQuench
2. customthe reaction
3. customPurify the crude material by column chromatography (silica gel, 4.5 cm×15 cm
4. washstep gradient elution with 0%, 5% and 10% methanol in dichloromethane
5. concentrationConcentrate the appropriate fractions