Sodium Carbonate → N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N'-[(3'-formyl-3-biphenylyl)methyl]-2,6-pyridinedicarboxamide

Participants

Reaction Conditions

Reaction Steps

A mixture of N-[(3-bromophenyl)methyl]-N′-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-2,6-pyridinedicarboxamide (600 mg, 0.967 mmol), (3-formylphenyl)boronic acid (188 mg, 1.257 mmol), Na2CO3 (307 mg, 2.90 mmol) and PdCl2(dppf) (70.7 mg, 0.097 mmol) was diluted in a mixture of 1,4-dioxane (9 mL) and water (3 mL) in a 20 mL Biotage microwave reaction tube. The mixture was degassed by bubbling argon through it for 5 minutes and it was then heated in a Biotage microwave at normal absorption for 30 min at 100° C. The crude mixture was filtered through a PL-Thiol MP SPE+ and was then washed with ethyl acetate and saturated NaHCO3. The organic layer was concentrated under vacuum to obtain the crude residue. It was purified with Gilson HPLC (with 0.1% TFA in the solvent) eluting with 15 to 80% CH3CN in water in a flow rate of 20 mL/min. The product fractions were dried under EZ2 Genevac and then combined to give N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N′-[(3′-formyl-3-biphenylyl)methyl]-2,6-pyridinedicarboxamide as a solid (278 mg, 44.5%). LC-MS m/z 646.1 (M+H)+, 0.91 min (ret time).

Provenance & Evidence