Acetamide → N-(5-((2-acetamidopyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide

Participants

Reaction Conditions

Reaction Steps

A mixture of Example C1 (0.300 g, 0.718 mmol), acetamide (0.127 g, 2.154 mmol), Cs2CO3 (0.468 g, 1.436 mmol) and Xantphos (0.046 g, 0.079 mmol) in dioxane (7 mL) was sparged with Ar under sonication. Pd2(dba)3 0.053 g, 0.057 mmol) was added, and the mixture was sparged again with Ar and heated at 93° C. overnight. The mixture was cooled to RT, and partitioned with EtOAc and brine. The aqueous layer was extracted with EtOAc (3×) and the combined organics were dried over Na2SO4, concentrated to dryness and purified by silica gel chromatography (MeOH/DCM). The material was suspended in 4:1 MeCN/water, frozen and lyophilized overnight, and further dried in a drying oven to afford N-(5-((2-acetamidopyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (0.287 g, 90%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 10.98 (s, 1 H), 10.57 (s, 1 H), 8.23 (dd, J=2.9, 0.5 Hz, 1 H), 8.19 (d, J=5.7 Hz, 1 H), 8.08 (dd, J=9.0, 0.5 Hz, 1 H), 7.72 (dd, J=9.0, 2.9 Hz, 1 H), 7.66 (d, J=2.3 Hz, 1H), 6.69 (dd, J=5.7, 2.4 Hz, 1 H), 3.94-3.79 (m, 5 H), 3.49-3.37 (m, 4 H), 2.04 (s, 3 H), 1.78-1.67 (m, 2 H), 1.64-1.58 (m, 2H); MS (ESI) m/z: 441.2 (M+H+).

Provenance & Evidence