A mixture of N-{[3-bromo-5-(methyloxy)phenyl]methyl}-N′-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-1,3-benzenedicarboxamide (782 mg, 1.20 mmol), 3-formylphenyl boronic acid (234 mg, 1.57 mmol), Na2CO3 (383 mg, 3.61 mmol), Pd(PPh3)4 (69.6 mg, 0.06 mmol), and water (3 mL) in dioxane (9 mL) was degassed for 5 min. This mixture was then heated under microwave for 30 min at 150° C. It was quenched with water and then extracted with ethyl acetate twice. The combined organic layers were washed with water and brine. The organic layer was filtered though a 0.45 μM filter and then concentrated to give a crude residue. It was then purified with Combi Flash chromatography eluting with 0 to 10% MeOH in DCM. The 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-5-(methyloxy)-3-biphenylyl]methyl}-1,3-benzenedicarboxamide as a solid (687 mg, 85%). LC-MS m/z 676 (M+H)+.
