Oxalyl chloride → N-((5-((2-acetamidopyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)tetrahydro-2H-pyran-4-carboxamide

Participants

Reaction Conditions

Reaction Steps

A solution of Example B5 (0.095 g, 0.737 mmol) in DCE (3 mL) was treated with oxalyl chloride (0.129 mL, 1.474 mmol) and heated at 80° C. for 3 h. The mixture was cooled to RT, concentrated to dryness, treated with a solution of Example A2 (0.09 g, 0.368 mmol) and TEA (0.205 mL, 1.474 mmol) in THF (4 mL) and stirred at RT for 0.5 h. The mixture was treated with satd. NaHCO3, 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/DCM). The material was suspended in MeCN/H2O, frozen and lyophilized to afford N-((5-((2-acetamidopyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)tetrahydro-2H-pyran-4-carboxamide (77 mg, 52%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.05 (s, 1H), 10.88 (s, 1H), 10.56 (s, 1H), 8.24 (d, J=2.9 Hz, 1H), 8.18 (d, J=5.7 Hz, 1H), 8.07 (d, J=9.0 Hz, 1H), 7.72 (dd, J=9.0, 2.9 Hz, 1H), 7.64 (d, J=2.4 Hz, 1H), 6.68 (dd, J=5.7, 2.4 Hz, 1H), 3.87 (m, 2H), 3.29-3.25 (m, 2H), 2.72-2.64 (m, 1H), 2.02 (s, 3H), 1.71 (m, 2H), 1.66-1.54 (m, 2H); MS (ESI) m/z: 400.2 (M+H+).

Provenance & Evidence