Example 54
A microwave vessel was charged with N-[3-(5-bromo-1H-pyrazolo[3,4-b]pyridine-3-carbonyl)-2,6-difluorophenyl]methanesulfonamide (60.0 mg, 0.139 mmol), XPhos Pd G3 (3.53 mg, 0.00417 mmol) and [4-(1H-tetrazol-5-yl)phenyl]boronic acid (31.7 mg, 0.167 mmol) and purged with argon. Degassed 1,4-dioxane (0.464 mL) and degassed aqueous 1.5 M Potassium Carbonate (0.325 mL, 0.487 mmol) were added and the mixture was heated to 110° C. under microwave irradiation for 60 minutes. After cooling, the mixture was diluted with EtOAc and neutralized with sat. NH4Cl solution. The organic phase was concentrated under reduced pressure and the product isolated by flash chromatography (DCM+MeOH (+1% formic acid) 5% to 15%), triturated with MeOH and dried at 100° C. in a vacuum oven to yield N-[2,6-difluoro-3-[5-[4-(1H-tetrazol-5-yl)phenyl]-1H-pyrazolo[3,4-b]pyridine-3-carbonyl]phenyl]methanesulfonamide (21.0 mg, 0.0423 mmol, 30% yield).
Analytical Data:
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- 1H NMR (200 MHz, DMSO) δ 14.85 (s, 1H), 9.75 (s, 1H), 9.10 (d, J=2.1 Hz, 1H), 8.86 (d, J=2.2 Hz, 1H), 8.25-8.00 (m, 4H), 7.97-7.81 (m, 1H), 7.41 (td, J=8.9, 1.3 Hz, 1H), 3.12 (s, 3H);
MS: [M−1]−=495.2.
A microwave vessel was charged with N-[3-(5-bromo-1H-pyrazolo[3,4-b]pyridine-3-carbonyl)-2,6-difluorophenyl]methanesulfonamide (60.0 mg, 0.139 mmol), XPhos Pd G3 (5.89 mg, 0.00696 mmol) and (4-Carbamoylphenyl)boronic acid (27.5 mg, 0.167 mmol) and purged with argon. Degassed 1,4-dioxane (0.464 mL) and degassed aqueous 1.5 M Potassium Carbonate (0.325 mL, 0.487 mmol) were added and the mixture was heated to 110° C. under microwave irradiation for 60 minutes. After cooling, the mixture was diluted with EtOAc and neutralized with sat. NH4Cl solution. The solvents were removed under reduced pressure and the product isolated by flash chromatography (DCM+MeOH, 5% to 15%) and dried at 100° C. in a vacuum oven to yield 4-[3-[2,4-difluoro-3-(methanesulfonamido)benzoyl]-1H-pyrazolo[3,4-b]pyridin-5-yl]benzamide (40.0 mg, 0.0789 mmol, 57% yield).
Analytical Data:
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- 1H NMR (200 MHz, DMSO) δ 9.06 (d, J=1.9 Hz, 1H), 8.82 (d, J=2.0 Hz, 1H), 8.14-7.80 (m, 6H), 7.49-7.33 (m, 2H), 3.11 (s, 3H);
MS: [M−1]−=470.3
A microwave vessel was charged with N-[3-(5-bromo-1H-pyrazolo[3,4-b]pyridine-3-carbonyl)-2,6-difluorophenyl]methanesulfonamide (60.0 mg, 0.139 mmol), XPhos Pd G3 (5.89 mg, 0.00696 mmol) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzenesulfonamide (47.3 mg, 0.167 mmol) and purged with argon. Degassed 1,4-dioxane (0.464 mL) and degassed aqueous 1.5 M potassium carbonate (0.325 mL, 0.487 mmol) were added and the mixture was heated to 110° C. under microwave irradiation for 60 minutes. After cooling, the mixture was diluted with EtOAc and neutralized with sat. NH4Cl solution. The solvents were removed under reduced pressure and the product isolated by flash chromatography (DCM+EtOAc, 50% to 100%) and dried at 100° C. in a vacuum oven to yield 4-[3-[2,4-difluoro-3-(methanesulfonamido)benzoyl]-1H-pyrazolo[3,4-b]pyridin-5-yl]benzenesulfonamide (31.0 mg, 0.0574 mmol, 41% yield). 1H NMR (200 MHz, DMSO) δ 9.07 (d, J=2.1 Hz, 1H), 8.84 (d, J=2.1 Hz, 1H), 8.12-7.78 (m, 4H), 7.50-7.32 (m, 2H), 3.11 (s, 3H); [M−1]−=506.2.
