Water → N-(2-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 Conditions

Reaction Steps

A mixture of 2-fluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)aniline (0.150 g, 0.528 mmol) and TEA (3.2 mL, 22.93 mmol) in DCM (5 mL) was cooled to 0° C., 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 Et2O, sonicated and the resulting solid collected via filtration to afford N-(2-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 (167 mg, 66%). 1H NMR (400 MHz, DMSO-d6): δ 10.74 (d, J=2.5 Hz, 1 H), 8.36 (d, J=5.7 Hz, 1 H), 8.25 (s, 1 H), 8.19 (t, J=9.1 Hz, 1 H), 7.95 (d, J=0.7 Hz, 1 H), 7.28 (dd, J=11.7, 2.7 Hz, 1 H), 7.22 (d, J=2.4 Hz, 1 H), 7.03 (dd, J=9.1, 2.5 Hz, 1 H), 6.67 (dd, J=5.7, 2.4 Hz, 1 H), 3.93-3.77 (m, 8 H), 3.46 (t, J=8.2 Hz, 2 H), 3.38 (dd, J=12.5, 10.6 Hz, 2 H), 1.71 (qd, J=12.2, 4.5 Hz, 2 H), 1.60-1.57 (m, 2H); MS (ESI) m/z: 481.2 (M+H+).

Provenance & Evidence