Pyridine → N-((5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)isobutyramide

Participants

Reaction Steps

A suspension of Example B7 (0.059 g, 0.673 mmol) in DCE (4 mL) was treated with oxalyl chloride (0.059 mL, 0.673 mmol), stirred at RT for 1 h, warmed to 80° C. for 2.5 h, cooled to RT and added drop-wise to a solution of Example A2 (0.15 g, 0.561 mmol) in THF (4 mL) and pyridine (0.226 mL, 2.81 mmol). The mixture was stirred at RT overnight, treated with satd. Na2CO3, extracted with EtOAc (4×) and the combined organics were dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM). The resulting material was dissolved in MeCN/H2O, frozen and lyophilized to afford N-((5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)isobutyramide (89 mg, 42%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.11 (s, 1H), 10.85 (s, 1H), 8.37 (d, J=5.7 Hz, 1H), 8.26-8.25 (m, 2H), 8.09 (d, J=9.0 Hz, 1H), 7.96 (d, J=0.7 Hz, 1H), 7.73 (dd, J=9.0, 3.0 Hz, 1H), 7.22 (d, J=2.4 Hz, 1H), 6.70 (dd, J=5.7, 2.4 Hz, 1H), 3.84 (s, 3H), 2.43 (m, 1H), 1.09 (d, J=6.8 Hz, 6H); MS (ESI) m/z: 381.1 (M+H+).

Provenance & Evidence