反应详情

A 0° C. solution of Example A2 (0.060 g, 0.224 mmol) and TEA (0.094 mL, 0.673 mmol) in DCM (1 mL) was treated with a solution of crude 3-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-2-oxoimidazolidine-1-carbonyl chloride (0.088 g, 0.337 mmol) in DCM (1 mL). The mixture was warmed to RT, stirred for 0.5 h, then concentrated to dryness and purified via silica gel chromatography (MeOH/DCM) to afford 3-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide as an off-white solid (74 mg, 67%). 1H NMR (400 MHz, DMSO-d6): δ 10.96 (s, 1 H), 8.36 (d, J=5.7 Hz, 1 H), 8.25 (s, 1 H), 8.21 (m, 1 H), 8.05 (m, 1 H), 7.96 (d, J=0.7 Hz, 1 H), 7.72 (dd, J=9.0, 2.9 Hz, 1 H), 7.23 (d, J=2.4 Hz, 1 H), 6.68 (dd, J=5.7, 2.4 Hz, 1 H), 4.04 (m, 1 H), 3.84 (s, 3 H), 3.84-3.75 (m, 2 H), 3.70-3.59 (m, 2 H), 3.46-3.39 (m, 2 H), 1.60-1.47 (m, 4 H), 1.18 (d, J=15.1 Hz, 6 H); MS (ESI) m/z: 492.2 (M+H+).

1. concentrationconcentrated to dryness
2. custompurified via silica gel chromatography (MeOH/DCM)