1-Methylpyrrolidine → N-((5-((2-(3-methylureido)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)pivalamide

Participants

Reaction Steps

A mixture of Example C2 (0.163 g, 0.394 mmol), methylamine hydrochloride (0.053 g, 0.789 mmol) and N-methylpyrrolidine (0.070 g, 0.828 mmol) in dioxane (3 mL) was heated at 80° C. overnight, cooled to RT, and concentrated to dryness. The residue was suspended in MeCN and the mixture was sonicated for a few minutes. The light beige solid was collected by filtration and washed with MeCN. This solid was partitioned with DCM and water with stirring for 15 min. The aqueous layer was separated and extracted with DCM (2×). The combined organics were dried (Na2SO4) and concentrated to dryness. The residue was suspended in MeCN/water, frozen and lyophilized to afford N-((5-((2-(3-methylureido)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)pivalamide as a white solid (0.199 g, 125%). 1H NMR (400 MHz, DMSO-d6): δ 11.20 (s, 1H), 10.50 (s, 1H), 9.20 s, (1H), 8.22 (d, J=2.9 Hz, 1H), 8.09-8.03 (m, 2H), 7.97-7.87 (m, 1H), 7.73 (d, J=2.9 Hz, 1H), 7.00 (s, 1H), 6.55 (dd, J=5.8, 2.4 Hz, 1H), 2.64 (d, J=4.6 Hz, 3H), 1.21 (s, 9H); MS (ESI) m/z: 387.2 (M+H+).

Provenance & Evidence