反应详情

温度

100 °C

N-[(3-Bromo-4-methylphenyl)methyl]-N′-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-2,6-pyridinedicarboxamide (1.86 g, 2.93 mmol), (3-formylphenyl)boronic acid (0.439 g, 2.93 mmol), potassium carbonate (1.215 g, 8.79 mmol), and Pd(Ph3P)4 (0.169 g, 0.147 mmol) were combined in three 10-20 mL Biotage microwave vials in 1,4-dioxane (27 mL) and water (9 mL). The vials were capped and the mixture was heated in the microwave at normal power at 100° C. for 15 min. The crude product was partitioned between EtOAc (200 mL) and water (70 mL). The phases were separated, and the organic phase was washed with water (2×50 mL), brine (50 mL), dried over anhydrous Na2SO4, filtered and evaporated to give the crude residues. It was taken up in DCM and absorbed on Isolute® Sorbent and purified by a CombiFlash on a 120 g silica column eluted with 0-10% MeOH/DCM. Product fractions were combined and concentrated under vacuum to give (N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N′-[(3′-formyl-6-methyl-3-biphenylyl)methyl]-2,6-pyridinedicarboxamide (1.85 g, 2.72 mmol, 93% yield)) as a white solid. LC-MS m/z 660 (M+H)+, 0.94 min (ret time).

1. customThe vials were capped
2. customThe crude product was partitioned between EtOAc (200 mL) and water (70 mL)
3. customThe phases were separated
4. washthe organic phase was washed with water (2×50 mL), brine (50 mL)
5. dry with materialdried over anhydrous Na2SO4
6. filtrationfiltered
7. customevaporated
8. customto give the crude residues
9. customabsorbed on Isolute® Sorbent
10. custompurified by a CombiFlash on a 120 g silica column
11. washeluted with 0-10% MeOH/DCM
12. concentrationconcentrated under vacuum