Trifluoroacetic acid → N-(2-methoxypyridin-4-yl)-4-(tetrahydro-2H-pyran-4-yloxy)-1H-pyrazolo[4,3-c]pyridin-3-amine

Participants

Reaction Steps

To a microwave tube was added 3-iodo-4-(tetrahydro-2H-pyran-4-yloxy)-1-trityl-1H-pyrazolo[4,3-c]pyridine (260 mg, 0.44 mmol), 4-amino-2-methoxy-pyridine (66 mg, 0.53 mmol), cesium carbonate (0.29 g, 0.88 mmol), XPhos (21 mg, 0.044 mmol), and tris(dibenzylideneacetone)dipalladium (20 mg, 0.022 mmol). The tube was then flushed with nitrogen for 1 minute before the addition of 1,4-dioxane (2.5 mL). The tube was sealed and irradiated in the microwave at 140° C. for 35 minutes. The reaction mixture was filtered through Celite® and concentrated. The crude material was filtered through a silica gel column (EtOAc) and concentrated. To the residue was added DCM (3 mL), triethylsilane (0.1 mL, 0.63 mmol) and trifluoroacetic acid (0.50 mL, 6.5 mmol). The mixture was stirred at room temperature for 15 minutes before concentrated under vacuum. The crude material was purified by reverse phase HPLC to give the title compound (11 mg, 7.3% over 2 steps). LC-MS (Method G): m/z=342.1 [M+H]+, 2.94 min. 1H-NMR (400 MHz, DMSO): δ 12.78 (s, 1H), 8.26 (s, 1H), 7.90 (d, J=5.6, 1H), 7.81 (d, J=6.0, 1H), 6.99 (d, J=6.0, 1H), 6.90 (d, J=5.4, 1H), 6.86 (s, 1H), 5.39 (m, 1H), 3.80 (m, 5H), 3.50 (m, 2H), 1.99 (m, 2H), 1.76 (m, 2H).

Provenance & Evidence