Trimethylacetamide → N-isopropyl-4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)picolinamide

Participants

Reaction Conditions

Reaction Steps

A suspension of 2,2,2-trimethylacetamide (0.149 g, 1.469 mmol) in DCE (4 mL) was treated with oxalyl chloride (0.129 mL, 1.469 mmol), heated at 80° C. for 1 h, cooled to RT, added drop-wise to a solution of 4-((6-aminopyridin-3-yl)oxy)-N-isopropylpicolinamide (0.2 g, 0.734 mmol) and DIEA (0.641 mL, 3.67 mmol) in dioxane (4 mL) and stirred at RT overnight. The mixture was diluted with EtOAc, washed with satd. NaHCO3, water, and 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-isopropyl-4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)picolinamide (0.241 g, 82%). 1H NMR (400 MHz, DMSO-d6): δ 11.24 (s, 1H), 10.45 (s, 1H), 8.50-8.49 (m, 2H), 8.30 (d, J=2.9 Hz, 1H), 8.11 (d, J=9.0 Hz, 1H), 7.78 (dd, J=9.0, 2.9 Hz, 1H), 7.40 (d, J=2.6 Hz, 1H), 7.21 (dd, J=5.6, 2.7 Hz, 1H), 4.05-4.04 (m, 1H), 1.21 (s, 9H), 1.15 (d, J=6.5 Hz, 6H); MS (ESI) m/z: 400.2 (M+H+).

Provenance & Evidence