Trimethylacetamide → HCID 86275147, compound

Participants

Reaction Conditions

Reaction Steps

A suspension of 2,2,2-trimethylacetamide (0.124 g, 1.222 mmol) in DCE (4 mL) was treated with oxalyl chloride (0.107 mL, 1.222 mmol), heated at 80° C. for 1 h, cooled to RT, added to a solution of 4-((6-aminopyridin-3-yl)oxy)-N-(1-methylpiperidin-4-yl)picolinamide (0.2 g, 0.611 mmol) and DIEA (0.533 mL, 3.05 mmol) in dioxane (4 mL) and stirred at RT overnight. The mixture was diluted with EtOAc, washed with satd. NaHCO3, 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 (MeOH/DCM/TEA). The material was treated with MeCN, sonicated and the resulting solid collected via filtration to afford N-(1-methylpiperidin-4-yl)-4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)picolinamide (186 mg, 67%). 1H NMR (400 MHz, DMSO-d6): δ 11.24 (s, 1H), 10.45 (s, 1H), 8.54-8.53 (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), 7.41 (d, J=2.6 Hz, 1H), 7.20 (dd, J=5.6, 2.6 Hz, 1H), 3.72-3.66 (m, 1H), 2.70 (d, J=11.0 Hz, 2H), 2.13 (s, 3H), 1.93 (t, J=11.1 Hz, 2H), 1.67-1.64 (m, 4H), 1.21 (s, 9H); MS (ESI) m/z: 455.2 (M+H+).

Provenance & Evidence