Sodium Carbonate → HCID 56598003, compound

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 (90 mg, 0.24 mmol), (4-fluorophenyl)boronic acid (33.7 mg, 0.24 mmol) in 1,4-dioxane (3 mL). PdCl2(dppf)-CH2Cl2 adduct (19.7 mg, 0.024 mmol) was added and the resulting mixture was degassed with nitrogen for 10 min. Sodium carbonate (77 mg, 0.72 mmol) was added, the vessel was sealed, and the mixture was heated at 85° C. for 2 hrs and then at 100° C. overnight. Added an additional 2 eq of boronic acid and 0.2 eq of PdCl2(dppf)-CH2Cl2 adduct. The contents were heated at 120° C. for 4 hr. and then irradiated (microwave) first at 160° C. for 90 min, and then at 190° C. for 2 hrs. After cooling to room temperature, the solids were filtered, washed with DMSO and the filtrate was evaporated. The crude product was purified first by reverse-phase HPLC (C18, 5% to 80% CH3CN in water with 0.1% TFA, 18 minute gradient) and then silica gel chromatography (eluent: gradient 0 to 90:10:1 DCM/MeOH/NH4OH). The collected solid was dried to afford the title compound (13 mg, 12%) as a white solid. LCMS E-S (M+H)=434.2. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.58 (br. s., 1H), 8.96 (t, J=4.67 Hz, 1H), 8.38 (s, 1H), 8.33 (dd, J=8.84, 5.56 Hz, 2H), 8.16 (s, 1H), 7.40 (t, J=8.84 Hz, 2H), 5.91 (s, 1H), 5.33 (dt, J=13.26, 6.76 Hz, 1H), 4.41 (d, J=4.55 Hz, 2H), 2.23 (s, 3H), 2.13 (s, 3H), 1.55 (d, J=6.57 Hz, 6H).

Provenance & Evidence