Pyridine → N-((5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)pivalamide

Participants

Reaction Steps

A suspension of 2,2,2-trimethylacetamide (0.045 g, 0.449 mmol) in DCE (4 mL) was treated with oxalyl chloride (0.039 mL, 0.449 mmol), stirred at RT for 1 h, heated to 80° C. for 2.5 h, then cooled to RT and added drop-wise to a solution of Example A2 (0.10 g, 0.374 mmol) in THF (4 mL) and pyridine (0.215 mL, 2.67 mmol). The mixture was stirred at RT for 1 h, treated with satd. NaHCO3, extracted with EtOAc (2×) and the combined organics were washed with brine, dried over Na2SO4 and concentrated to dryness. The material was treated with MeCN, sonicated, and the resulting solid collected via filtration and dried to afford N-((5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)pivalamide (106 mg, 72%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.22 (s, 1H), 10.44 (s, 1H), 8.37 (d, J=5.7 Hz, 1H), 8.27-8.25 (m, 2H), 8.09 (d, J=9.0 Hz, 1H), 7.96 (s, 1H), 7.74 (dd, J=9.0, 2.9 Hz, 1H), 7.23 (d, J=2.4 Hz, 1H), 6.70 (dd, J=5.7, 2.4 Hz, 1H), 3.84 (s, 3H), 1.21 (s, 9H); MS (ESI) m/z: 395.2 (M+H+).

Provenance & Evidence