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

Participants

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) and {4-[(methylsulfonyl)amino]phenyl}boronic acid (43.1 mg, 0.2 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 reaction mixture was irradiated (microwave) at 150° C. for 25 min. After cooling, 2 mL of water was added to the black mixture and solids that precipitated were filtered. DCM/MeOH (1:1) was added, the mixture was pre-absorbed on silica gel and purified by silica gel chromatography (eluent: gradient 0 to 90:10:1 DCM/MeOH/NH4OH). The isolated product was suspended in EtOAc heated, and sonicated. Some hexanes was added and the contents allowed to cool to room temperature. Solids that precipitated were filtered. The solid was then suspended in EtOH, heated, and sonicated. After cooling to room temperature, the solids were filtered and dried to afford the title compound (38 mg, 36%) as a beige solid. LCMS E-S (M+H)=509.0. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.57 (s, 1H), 10.05 (br. s., 1H), 8.93 (t, J=4.93 Hz, 1H), 8.35 (s, 1H), 8.24 (m, J=8.59 Hz, 2H), 8.11 (s, 1H), 7.37 (m, J=8.84 Hz, 2H), 5.91 (s, 1H), 5.32 (quin, J=6.69 Hz, 1H), 4.41 (d, J=4.80 Hz, 2H), 3.08 (s, 3H), 2.23 (s, 3H), 2.13 (s, 3H), 1.55 (s, 3H), 1.54 (s, 3H).

Provenance & Evidence