Water → N-[(4,6-Dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-6-{4-[(methylamino)sulfonyl]phenyl}-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide

Participants

Reaction Conditions

Reaction Steps

In a 25 mL sealable tube under nitrogen were combined 6-chloro-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide (75 mg, 0.2 mmol), {4-[(methylamino)sulfonyl]phenyl}boronic acid (69 mg, 0.32 mmol) in DME/water (3 ml:1 ml). PdCl2(dppf)-CH2Cl2 adduct (8.2 mg, 0.01 mmol) was added and the resulting mixture was degassed with nitrogen for 10 min. Sodium bicarbonate (50.6 mg, 0.6 mmol) was added, the vessel was sealed, and the insoluble mixture was heated in a microwave at 150° C. for 30 min. After cooling, 2 mL of water was added to the mixture and solids that precipitated were filtered. DCM/MeOH (1:1) was added and the solution was filtered through a pad of silica gel and the filtrate was evaporated. The residue was purified by silica gel chromatography (eluent: gradient of 0 to 90:10 DCM/MeOH) and the isolated solid triturated in EtOAc. The solids were filtered and dried to afford the title compound (29 mg, 28%) as an off-white solid. LCMS E-S (M+H)=509.0. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.58 (br. s., 1 H), 8.99 (t, J=4.93 Hz, 1 H), 8.47 (m, J=8.59 Hz, 2 H), 8.43 (s, 1 H), 8.25 (s, 1 H), 7.95 (m, J=8.59 Hz, 2 H), 7.60 (br. s., 1 H), 5.91 (s, 1 H), 5.36 (quin, J=6.69 Hz, 1 H), 4.42 (d, J=4.80 Hz, 2 H), 2.46 (s, 3 H), 2.23 (s, 3 H), 2.13 (s, 3 H), 1.56 (d, J=6.82 Hz, 6 H).

Provenance & Evidence