Oxalyl chloride → N-methyl-4-((6-(3-(1-(trifluoromethyl)cyclobutanecarbonyl)ureido)pyridin-3-yl)oxy)picolinamide

Participants

Reaction Steps

A solution of 1-trifluoromethyl-cyclobutane-1-carboxylic acid (0.413 g, 2.457 mmol) in DCM (8 mL) was treated with oxalyl chloride (0.179 mL, 2.047 mmol) and DMF (1 drop), stirred for at RT for 2 h, treated with silver cyanate (0.982 g, 6.55 mmol), stirred at RT for 1 h, treated with a solution of 4-((6-aminopyridin-3-yl)oxy)-N-methylpicolinamide (0.2 g, 0.819 mmol) and DIEA (0.858 mL, 4.91 mmol) in dioxane (8 mL) and stirred at RT overnight. The mixture was diluted with EtOAc, the solids removed via filtration through diatomaceous earth and washed with EtOAc. The filtrate was washed with satd. NaHCO3, water, then brine and the combined aqueous washes were back-extracted with EtOAc. The combined organics were dried over Na2SO4, concentrated to dryness and purified by silica gel chromatography (EtOAc/DCM) to afford N-methyl-4-((6-(3-(1-(trifluoromethyl)cyclobutanecarbonyl)ureido)pyridin-3-yl)oxy)picolinamide (0.259 g, 72%). 1H NMR (400 MHz, DMSO-d6): δ 11.16 (br s, 1H), 10.87 (s, 1H), 8.79 (d, J=5.1 Hz, 1H), 8.53 (d, J=5.6 Hz, 1H), 8.32 (d, J=2.9 Hz, 1H), 8.08 (d, J=9.1 Hz, 1H), 7.81 (dd, J=9.0, 2.9 Hz, 1H), 7.41 (d, J=2.6 Hz, 1H), 7.19 (dd, J=5.6, 2.7 Hz, 1H), 2.78 (d, J=4.8 Hz, 3H), 2.67 (t, J=10.5 Hz, 2H), 2.41 (m, 2H), 1.90-1.87 (m, 2H); MS (ESI) m/z: 438.2 (M+H+).

Provenance & Evidence