Acetamide → N-(5-((2-acetamidopyridin-4-yl)oxy)-6-methylpyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide

Participants

Reaction Conditions

Reaction Steps

To a degassed solution of Example C3 (0.12 g, 0.278 mmol) in dioxane (3 mL) was added acetamide (0.066 g, 1.111 mmol), Cs2CO3 (0.091 g, 0.278 mmol), X-Phos (0.013 g, 0.028 mmol), Pd2(dba)3 (0.025 g, 0.028 mmol) and the mixture was stirred at 80° C. for 16 h. The mixture was diluted with EtOAc (5 mL) and filtered through a pad of diatomaceous earth. The filter pad was washed with EtOAc (3×8 mL). The combined filtrates were washed with water and brine, dried (Na2SO4) and concentrated in vacuo. The residue was purified by chromatography (0-5% MeOH/DCM) to afford a colorless foam. The foam was dissolved in MeCN-water and the solution was frozen and lyophilized to provide N-(5-((2-acetamidopyridin-4-yl)oxy)-6-methylpyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (83 mg, 66%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 10.89 (s, 1 H), 10.54 (s, 1 H), 8.16 (d, J=5.7 Hz, 1 H), 7.88 (d, J=8.8 Hz, 1 H), 7.60 (d, J=8.8 Hz, 1 H), 7.57 (d, J=2.4 Hz, 1 H), 6.61 (dd, J=5.7, 2.4 Hz, 1 H), 3.93-3.78 (m, 5H), 3.48-3.33 (m, 4 H), 2.20 (s, 3 H), 2.02 (s, 3 H), 1.78-1.67 (m, 2 H), 1.64-1.58 (m, 2H); MS (ESI) m/z: 455.1 (M+H+).

Provenance & Evidence