反应详情

A 0° C. mixture of 3-chloro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)aniline (0.150 g, 0.499 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) to afford N-(3-chloro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)phenyl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (176 mg, 71%). 1H NMR (400 MHz, DMSO-d6): δ 10.57 (s, 1 H), 8.34 (d, J=5.7 Hz, 1 H), 8.25 (s, 1 H), 7.96 (s, 1 H), 7.92 (d, J=2.6 Hz, 1 H), 7.46 (dd, J=8.8, 2.6 Hz, 1H), 7.32 (d, J=8.8 Hz, 1 H), 7.19 (d, J=2.4 Hz, 1 H), 6.55 (dd, J=5.7, 2.5 Hz, 1 H), 3.94-3.76 (m, 8 H), 3.46 (t, J=8.2 Hz, 2 H), 3.37 (t, J=11.7 Hz, 2 H), 1.76-1.66 (m, 2 H), 1.59 (d, J=12.4 Hz, 2H); MS (ESI) m/z: 497.2 (M+H+).

1. stirringstirred for 10 min
2. customthe layers separated
3. dry with materialthe organic layer dried over Na2SO4
4. concentrationconcentrated to dryness
5. custompurified via silica gel chromatography (MeOH/DCM)