Water → N-((5-((2-(cyclopropanecarboxamido)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)tetrahydro-2H-pyran-4-carboxamide

Participants

Reaction Steps

A solution of Example B5 (0.096 g, 0.740 mmol) in DCE (3 mL) was treated with oxalyl chloride (0.081 mL, 0.925 mmol), stirred at RT for 0.5 h, then heated at 75° C. for 3 h. The mixture was cooled to RT, treated with a solution of Example A7 (0.1 g, 0.370 mmol) and TEA (0.155 mL, 1.110 mmol) in THF (5 mL) and stirred at RT for 1 h. The mixture was treated with water, extracted with EtOAc (2×) and the combined organics were washed with brine, dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/EtOAc). The material was suspended in 30% MeCN/water (4 mL), sonicated and the resulting solid collected via filtration and dried to afford N-((5-((2-(cyclopropanecarboxamido)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)tetrahydro-2H-pyran-4-carboxamide (61 mg, 39%). 1H NMR (400 MHz, DMSO-d6): δ 11.05 (s, 1H), 10.88 (s, 1H), 10.86 (s, 1H), 8.24 (d, J=2.9 Hz, 1H), 8.19 (d, J=5.7 Hz, 1H), 8.07 (d, J=9.0 Hz, 1H), 7.72 (dd, J=9.0, 2.9 Hz, 1H), 7.62 (d, J=2.4 Hz, 1H), 6.72 (dd, J=5.7, 2.4 Hz, 1H), 3.88 (m, 2H), 3.31-3.29 (m, 2H), 2.68-2.66 (m, 1H), 1.96-1.95 (m, 1H), 1.73-1.72 (m, 2H), 1.62-1.60 (m, 2H), 0.75 (d, J=6.2 Hz, 4H); MS (ESI) m/z: 426.2 (M+H+).

Provenance & Evidence