反应详情

温度

100 °C

To a solution of 4,6-dichloro-3-[(trans-4-methylcyclohexyl)methyl]-2-[(3R)-3-phenylmorpholin-4-yl]-3H-imidazo[4,5-c]pyridine (Example 2.1, Step 2; 400 mg, 0.87 mmol) in DMSO (5 mL) was added cyclobutylmethanol (337 mg, 3.92 mmol), Cs2CO3 (848 mg, 2.61 mmol) and BINAP (108 mg, 0.17 mmol). The reaction mixture was deoxygenated by purging with nitrogen for 10 minutes and then Pd2dba3 (159 mg, 0.17 mmol) was added. The reaction was again deoxygenated for 5 minutes by purging with nitrogen. The reaction flask was sealed, and the mixture was heated at 100° C. for 16 h. The reaction mixture was then cooled, diluted with water (30 ml) and EtOAc (60 mL), and the organic layer was separated. The organic layer was washed with water (2×10 mL), followed by saturated brine (2×30 mL). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated. The residue was purified on a silica gel column (30% EtOAc/petroleum ether) to yield 6-chloro-4-(cyclobutylmethoxy)-3-[(trans-4-methylcyclohexyl)methyl]-2-[(3R)-3-phenylmorpholin-4-yl]-3H-imidazo[4,5-c]pyridine. MS ES/APCl calc'd. for C29H37ClN4O2 [M+H]+ 509. found 509.

1. customThe reaction mixture was deoxygenated
2. customby purging with nitrogen for 10 minutes
3. customThe reaction was again deoxygenated for 5 minutes
4. customby purging with nitrogen
5. customThe reaction flask was sealed
6. temperatureThe reaction mixture was then cooled
7. additiondiluted with water (30 ml) and EtOAc (60 mL)
8. customthe organic layer was separated
9. washThe organic layer was washed with water (2×10 mL)
10. dry with materialThe organic layer was dried over anhydrous Na2SO4
11. filtrationfiltered
12. concentrationconcentrated
13. customThe residue was purified on a silica gel column (30% EtOAc/petroleum ether)