Acetonitrile → 5-(4-(Tetrahydro-2H-pyran-4-yloxy)-1H-pyrazolo[4,3-c]pyridin-3-yl)quinoline

Participants

Reaction Conditions

Reaction Steps

To a microwave tube was added 3-iodo-4-(tetrahydro-2H-pyran-4-yloxy)-1-trityl-1H-pyrazolo[4,3-c]pyridine (120 mg, 0.20 mmol), quinolin-5-ylboronic acid (43 mg, 0.25 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium (14 mg, 0.02 mmol), a 2 M aqueous solution of sodium carbonate (0.20 mL) and acetonitrile (1.5 mL, 0.029 mmol). The tube was then sealed and the reaction was irradiated in a microwave reactor at 140° C. for 30 minutes. The reaction mixture was filtered through Celite® and concentrated. The crude residue was then dissolved in DCM (3 mL) and cooled to 0° C. To the cooled reaction mixture was added triethylsilane (0.13 mL, 0.80 mmol) and trifluoroacetic acid (3.0 mL, 0.039 mmol). The mixture was stirred at room temperature for 30 minutes before concentrated under vacuum. The resulting residue was re-suspended in methanol and filtered to remove insoluble solids. The filtrate was concentrated and purified by reverse-phase HPLC to give the title compound (30 mg, 43%). LC-MS (Method G): m/z=347.1 [M+H]+; 2.98 min. 1H-NMR (400 MHz, DMSO): δ 13.69 (s, 1H), 8.94 (s, 1H), 8.23 (d, J=8.4, 1H), 8.14 (d, J=8.3, 1H), 7.89 (m, 2H), 7.78 (d, J=6.8, 1H), 7.49 (m, 1H), 7.22 (m, 1H), 5.28 (m, 1H), 3.24 (m, 2H), 3.06 (m, 2H), 1.69 (m, 2H), 1.17 (m, 3H).

Provenance & Evidence