Sodium Carbonate → HCID 178489374, compound

Participants

Reaction Steps

A mixture of 3-(2-methoxy-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridine (254 mg, 0.53 mmol), a mixture of 2-(3-bromo-phenyl)-1-methyl-1H-imidazole and 2-(3-chloro-phenyl)-1-methyl-1H-imidazole (200 mg, 0.48 mmol each) and 1,1′-bis(diphenylphosphino)-ferrocenepalladium(II)-dichloride dichlormethane adduct (20 mg, 0.024 mmol) in acetonitrile (5 mL) and aqueous solution of sodium carbonate (2M, 0.48 mL) was irradiated in a Personal Chemistry Optimizer at 120° C. for 30 min. Sodium sulfate was added to the crude reaction mixture and the solids were filtered over Celite. The solids were washed with acetonitrile and the combined filtrate was concentrated. Purification by flash silica gel chromatography using a gradient of ethyl acetate and hexanes afforded a white solid which was dissolved in 5 mL trifluoroacetic acid. The mixture was stirred at room temperature for 1 h and the solvent was evaporated. The crude product was dissolved in 1 mL of methanol and 200 μL of ethylenediamine was added. After 15 min, 1 mL of DMSO was added and the mixture was directly purified by mass-triggered preparative reverse phase HPLC to give 3-(2-Methoxy-phenyl)-5-[3-(1-methyl-1H-imidazol-2-yl)-phenyl]-1H-pyrazolo[3,4-b]pyridine formic acid salt as a colorless solid (82 mg, 0.019 mmol, 40% yield). As the formic acid salt: 1H NMR (500 MHz, DMSO-d6) δ 8.89 (d, J=2 Hz, 1H), 8.37 (d, J=2 Hz, 1H), 8.15 (s, 1H), 8.01 (t, J=2 Hz, 1H), 7.79 (dt, J1=8 Hz, J2=1 Hz, 1H), 7.70 (dt, J1=8 Hz, J2=1.5 Hz, 1H), 7.65 (dd, J1=7.5 Hz, J2=2 Hz, 1H), 7.59 (t, J=7.5 Hz, 1H), 7.28 (d, J=1.5 Hz, 1H), 7.20 (d, J=8 Hz, 1H), 7.08 (td, J1=7.5 Hz, J2=1 Hz, 1H), 7.0 (d, J=1 Hz, 1H), 3.84 (s, 3H), 3.82 (s, 3H). MS: m/z 382.2 (M+H+).

Provenance & Evidence