反应详情

To a solution of 1-(8-{2-[4-(3-fluoro phenyl)piperidin-4-yl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole dihydrochloride II (130 mg, 0.25 mmol, 1 eq.) in dimethylformamide (4 mL) was added 3-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid, 1a, (50 mg, 0.27 mmol, 1 eq.) and N,N-diisopropylethyl amine (180 μL, 1.0 mmol, 4 eq.). After stirring at RT for several min, O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyl-uroniumhexafluorophosphate (95 mg, 0.25 mmol, 1 eq.) was added and the reaction was stirred for 2 h. The mixture was partitioned between dichloromethane and satd. aq. NaHCO3. The organic layer was dried and concentrated and the residue was purified by prep. HPLC (Method Y) to provide 1-{8-[2-(4-(3-fluorophenyl)-1-{[3-(trifluoromethyl)pyridin-2-yl]carbonyl}piperidin-4-yl)ethyl]-8-azabicyclo[3.2.1]oct-3-yl}-2-methyl-1H-benzimidazole 1 as a white solid (30 mg, 20% yield).

1. additionwas added
2. customThe mixture was partitioned between dichloromethane
3. customThe organic layer was dried
4. concentrationconcentrated
5. customthe residue was purified by prep