反应详情

To a solution of 2-bromo-4-(5-chloropyridin-3-yl)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile (Preparative Example 3.1, 500 mg, 1.35 mmol) in toluene (5 mL), was added aniline (0.13 mL, 1.48 mmol) and chloro[2-(dicyclohexylphosphino)-3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl][2-(2-aminoethyl)phenyl]palladium(II) (BrettPhos precatalyst, 107 mg, 0.135 mmol), and the reaction was deoxygenated by purging with nitrogen for 10 minutes. Sodium tert-butoxide (194 mg, 2.02 mmol) in THF (2 mL) was added, and the reaction was again purged with nitrogen for 5 minutes. The reaction flask was sealed, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with EtOAc (100 mL) and the layers were separated. The organic layer was washed with water (2×25 mL) followed by saturated brine solution (25 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated. The crude product was purified on a silica gel column (30% EtOAc/petroleum ether) to afford 4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-2-(phenylamino)-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ES/APCl calc'd. for C26H25ClN6 [M+H]+ 457. found 457.

1. customthe reaction was deoxygenated
2. customby purging with nitrogen for 10 minutes
3. customthe reaction was again purged with nitrogen for 5 minutes
4. customThe reaction flask was sealed
5. additionThe reaction mixture was diluted with EtOAc (100 mL)
6. customthe layers were separated
7. washThe organic layer was washed with water (2×25 mL)
8. dry with materialThe organic layer was dried over anhydrous Na2SO4
9. concentrationconcentrated
10. customThe crude product was purified on a silica gel column (30% EtOAc/petroleum ether)