Water → 1-methyl-N-(4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)piperidine-4-carboxamide

Participants

Reaction Steps

A solution of 2,2,2-trimethylacetamide (0.042 g, 0.412 mmol) in DCE (2 mL) was treated with oxalyl chloride (0.036 mL, 0.412 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 mixture of Example A8 (0.09 g, 0.275 mmol) and TEA (0.1 mL) in THF (2 mL) and stirred at RT for 1.5 h. The mixture was treated with water, extracted with EtOAc (3×) and the combined organics were dried over Na2SO4 and concentrated to dryness. The material was layered with EtOAc, allowed to stand overnight and the resulting solid collected via filtration to afford 1-methyl-N-(4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)piperidine-4-carboxamide (35 mg, 27%) as a peach-colored solid. 1H NMR (400 MHz, DMSO-d6): δ 11.24 (s, 1H), 10.52 (s, 1H), 10.50 (s, 1H), 8.25 (d, J=2.9 Hz, 1H), 8.20 (d, J=5.7 Hz, 1H), 8.10 (d, J=9.0 Hz, 1H), 7.74 (dd, J=9.0, 2.9 Hz, 1H), 7.65 (d, J=2.4 Hz, 1H), 6.73 (dd, J=5.7, 2.4 Hz, 1H), 2.77 (m, 2H), 2.38 (m, 1H), 2.13 (s, 3H), 1.82 (m, 2H), 1.66 (m, 2H), 1.55 (m, 2H), 1.22 (s, 9H); MS (ESI) m/z: 455.3 (M+H+).

Provenance & Evidence