Potassium Carbonate → 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

Participants

Reaction Conditions

Reaction Steps

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).

Provenance & Evidence