Morpholine → N-(4-((2-methyl-6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)morpholine-4-carboxamide

Participants

Reaction Conditions

Reaction Steps

A mixture of prop-1-en-2-yl (4-((2-methyl-6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)carbamate (0.164 g, 0.384 mmol), morpholine (0.067 g, 0.767 mmol) and N-methylpyrrolidine (3.27 mg, 0.038 mmol) in dioxane (4 mL) was heated at 80° C. overnight. The mixture was cooled to RT, concentrated to dryness and purified twice via silica gel chromatography (MeOH/DCM, then MeOH/EtOAc). The material was treated with satd. NaHCO3, extracted with DCM (4×) and the combined organics were dried over Na2SO4, concentrated to dryness and further purified via silica gel chromatography (MeOH/DCM) to afford N-(4-((2-methyl-6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)morpholine-4-carboxamide (21 mg, 12%). 1H NMR (400 MHz, DMSO-d6): δ 11.14 (s, 1H), 10.39 (s, 1H), 9.27 (s, 1H), 8.11 (d, J=5.7 Hz, 1H), 7.90 (d, J=8.8 Hz, 1H), 7.61 (d, J=8.8 Hz, 1H), 7.27 (d, J=2.3 Hz, 1H), 6.57 (dd, J=5.7, 2.4 Hz, 1H), 3.53 (m, 4H), 3.38 (m, 4H), 2.23 (s, 3H), 1.21 (s, 9H); MS (ESI) m/z: 457.2 (M+H+).

Provenance & Evidence