Potassium Carbonate → 1-methyl-N-(4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)-1H-imidazole-4-carboxamide

Participants

Reaction Conditions

Reaction Steps

A mixture of Example C1 (0.15 g, 0.455 mmol), 1-methyl-1H-imidazole-4-carboxylic acid (0.172 g, 1.366 mmol), TBTU (0.439 g, 1.366 mmol) and DIEA (0.476 mL, 2.73 mmol) in DMF (5 mL) was stirred at RT for 2 h, then heated at 60° C. overnight. Additional 1-methyl-1H-imidazole-4-carboxylic acid (0.172 g, 1.366 mmol) and TBTU (0.439 g, 1.366 mmol) were added and the mixture heated at 60° C. overnight. The mixture was cooled to RT, treated with 10% K2CO3, extracted with DCM (4×) and the combined organics were washed with brine, dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM). The material was further purified via preparative TLC (MeOH/DCM) to afford 1-methyl-N-(4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)-1H-imidazole-4-carboxamide (52 mg, 26%). 1H NMR (400 MHz, DMSO-d6): δ 11.23 (s, 1H), 10.44 (s, 1H), 9.47 (s, 1H), 8.29 (d, J=2.9 Hz, 1H), 8.22 (d, J=5.8 Hz, 1H), 8.10 (d, J=9.0 Hz, 1H), 7.85 (d, J=1.2 Hz, 1H), 7.78-7.77 (m, 2H), 7.75 (d, J=2.4 Hz, 1H), 6.75 (dd, J=5.8, 2.4 Hz, 1H), 3.71 (s, 3H), 1.22 (s, 9H); MS (ESI) m/z: 438.2 (M+H+).

Provenance & Evidence