Trimethylacetamide → N-((5-((2-isobutyramidopyridin-4-yl)oxy)-6-methylpyridin-2-yl)carbamoyl)pivalamide

Participants

Reaction Steps

A solution of 2,2,2-trimethylacetamide (0.046 g, 0.454 mmol) in DCE (2 mL) was treated with oxalyl chloride (0.040 mL, 0.454 mmol), stirred at RT for 0.5 h, then heated at 75° C. for 1 h. The mixture was cooled to RT, added to a solution of N-(4-((6-amino-2-methylpyridin-3-yl)oxy)pyridin-2-yl)isobutyramide (0.10 g, 0.349 mmol) and TEA (0.1 mL, 0.70 mmol) in THF (2 mL) and stirred at RT for 1 h. The mixture was concentrated to dryness, the residue treated with EtOAc, washed with brine, dried over Na2SO4 and concentrated to dryness. The material was treated with EtOAc, allowed to stand at RT overnight and the resulting solid collected via filtration and dried to afford N-((5-((2-isobutyramidopyridin-4-yl)oxy)-6-methylpyridin-2-yl)carbamoyl)pivalamide (63 mg, 42%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.17 (s, 1H), 10.50 (s, 1H), 10.42 (br s, 1H), 8.18 (d, J=5.7 Hz, 1H), 7.92 (m, 1H), 7.63 (d, J=8.8 Hz, 1H), 7.60 (d, J=2.4 Hz, 1H), 6.66 (dd, J=5.7, 2.4 Hz, 1H), 2.69 (m, 1H), 2.24 (s, 3H), 1.22 (s, 9H), 1.02 (d, J=6.8 Hz, 6H); MS (ESI) m/z: 414.2 (M+H+).

Provenance & Evidence