Pyridine → N-((5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)-3-(1-(trifluoromethyl)cyclopropyl)propanamide

Participants

Reaction Steps

A suspension of Example B2 (0.081 g, 0.449 mmol) in DCE (6 mL) was treated with oxalyl chloride (0.039 mL, 0.449 mmol), stirred at RT for 0.5 h, then heated to 83° C. for 3 h. The mixture was cooled to RT, added drop-wise to a solution of Example A2 (0.10 g, 0.374 mmol) and pyridine (0.151 mL, 1.871 mmol) in THF (6 mL) and stirred at RT for 1 h. The mixture was treated with satd. NaHCO3, extracted with EtOAc (3×) and the combined organics were dried over Na2SO4 and concentrated to dryness. The material was treated with MeCN, sonicated for 5 min and the resulting solid collected via filtration and dried to afford N-((5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)-3-(1-(trifluoromethyl)cyclopropyl)propanamide (98 mg, 55%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 10.98 (s, 1H), 10.89 (s, 1H), 8.37 (d, J=5.7 Hz, 1H), 8.27-8.25 (m, 2H), 8.08 (d, J=9.0 Hz, 1H), 7.96 (s, 1H), 7.73 (dd, J=9.0, 2.9 Hz, 1H), 7.23 (d, J=2.4 Hz, 1H), 6.70 (dd, J=5.7, 2.4 Hz, 1H), 3.84 (s, 3H), 2.57 (t, J=8.0 Hz, 2H), 1.87 (t, J=8.0 Hz, 2H), 0.91 (m, 2H), 0.78 (m, 2H); MS (ESI) m/z: 475.1 (M+H+).

Provenance & Evidence