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

Participants

Reaction Conditions

Reaction Steps

5-Bromo-N-methyl-2-pyridinesulfonamide (225 mg, 0.896 mmol), Bis(pinacolato)diboron (296 mg, 1.165 mmol), Pd(dppf) (35.7 mg, 0.044 mmol) and potassium acetate (264 mg, 2.69 mmol) were suspended in 1,4-Dioxane (8 mL), and stirred with heating at 100° C. for 1 h. After cooling to room temperature, 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 (368 mg, 0.986 mmol), bis(triphenylphosphine)palladium(II) chloride (73.2 mg, 0.090 mmol) and sodium bicarbonate (226 mg, 2.69 mmol) were added, followed by DME (5 mL) and water (3 mL). The reaction mixture was irradiated (microwave) at 120° C. for 2 h. The reaction mixture was cooled cooled to room temperature and filtered through Na2SO4. The contents were purified directly by silica gel chromatography (eluent: 15% MeOH/CH2Cl2) to furnish the desired product as a grey solid after evaporation and precipitation from warm EtOAc/MeOH (1:9). The product was again purified by silica gel chromatography (eluent: 5% MeOH/CH2Cl2) to afford the final product as a white solid, 83 mg (18%). LCMS E-S (M+H)=510.0 1H NMR (400 MHz, DMSO-d6) δ ppm 11.59 (br. s., 1H), 9.56 (d, J=1.52 Hz, 1H), 8.96 (s, 1H), 8.86 (dd, J=8.34, 2.27 Hz, 1H), 8.46 (s, 1H), 8.34 (s, 1H), 8.12 (d, J=8.34 Hz, 1H), 7.85 (br. s., 1H), 5.91 (s, 1H), 5.27-5.46 (m, 1H), 4.43 (d, J=4.80 Hz, 2H), 2.60 (s, 3H), 2.23 (s, 3H), 2.13 (s, 3H), 1.56 (d, 6H).

Provenance & Evidence