Water → N-(3-fluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)phenyl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide

Participants

Reaction Steps

A 0° C. mixture of 3-fluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)aniline (0.150 g, 0.528 mmol) and TEA (0.1 mL, 0.716 mmol) in DCM (5 mL) was treated with a solution of Example B2 (0.164 g, 0.705 mmol) in DCM (1.5 mL), warmed to RT and stirred for 1 h. The mixture was treated with water, stirred for 10 min, the layers separated and the organic layer dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM). The material was treated with DCM, sonicated and allowed to evaporate overnight. The residue was treated with Et2O, sonicated and the resulting solid collected via filtration to afford N-(3-fluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)phenyl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (154 mg, 61%). 1H NMR (400 MHz, DMSO-d6): δ 10.59 (s, 1 H), 8.35 (d, J=5.7 Hz, 1 H), 8.25 (s, 1 H), 7.95 (s, 1 H), 7.74 (dd, J=12.9, 2.2 Hz, 1 H), 7.36-7.28 (m, 2 H), 7.22 (d, J=2.5 Hz, 1 H), 6.62 (dd, J=5.7, 2.5 Hz, 1 H), 3.94-3.82 (m, 6 H), 3.79 (m, 2 H), 3.45 (m, 2 H), 3.37 (m, 2 H), 1.72 (m, 2 H), 1.59 (m, 2H); MS (ESI) m/z: (M+H+): 481.2.

Provenance & Evidence