Water → 6-{4-[(Dimethylamino)sulfonyl]phenyl}-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-1-(1-methylethyl)-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]-3-methyl-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide (75 mg, 0.19 mmol) and N,N-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzenesulfonamide (90 mg, 0.29 mmol) in DME/water (3 ml:1 ml). PdCl2 (dppf)-CH2Cl2 adduct (7.9 mg, 0.009 mmol) was added and the resulting mixture was degassed with nitrogen for 10 min. Sodium bicarbonate (48.7 mg, 0.58 mmol) was added, the vessel was sealed, and the reaction mixture was irradiated (microwave) at 150° C. for 30 min. After cooling, 2 mL of water was added 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 treated with EtOH/EtOAc (1:1), the solids filtered and washed with EtOAc and DCM, and then dried to afford the title compound (83 mg, 78%) as a white solid. LCMS E-S (M+H)=537.1. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.54 (s, 1H) 8.79 (t, J=4.93 Hz, 1H) 8.47 (m, J=8.59 Hz, 2H) 7.90 (m, J=8.59 Hz, 2H) 7.80 (s, 1H) 5.89 (s, 1H) 5.28 (quin, J=6.69 Hz, 1H) 4.40 (d, J=5.05 Hz, 2H) 2.66 (s, 6H) 2.47 (s, 3H) 2.25 (s, 3H) 2.12 (s, 3H) 1.53 (s, 3H) 1.51 (s, 3H).

Provenance & Evidence