Acetamide → HCID 54576083, compound

Participants

Reaction Conditions

Reaction Steps

N-(4-(2-chloropyridin-4-yloxy)-2,5-difluorophenyl)-N′-phenylcyclopropane-1,1-dicarboxamide (0.162 g, 0.365 mmol), acetamide (0.108 g, 1.825 mmol), cesium carbonate (0.178 g, 0.548 mmol), and xantphos (0.021 g, 0.036 mmol) were combined in dry dioxane (2.61 mL) and argon was bubbled through the mixture for 5 minutes. Palladium acetate (6.15 mg, 0.027 mmol) was added, and argon was bubbled through the mixture for an additional 5 minutes. The reaction flask was fitted with a reflux condenser and a balloon of argon and the mixture was heated at 100° C. for 20 hours. The reaction mixture was cooled to room temperature and partitioned between a 4:1 mixture of ethyl acetate and THF (50 mL) and water (50 mL). The aqueous layer was removed and the organic layer was washed with additional water (50 mL) and brine (50 mL). The organic layer was dried over magnesium sulfate and evaporated under reduced pressure to yield a light peach-colored film. Dichloromethane (10 mL) was added and after a few minutes solid began to precipitate. Sonication was used to precipitate out more solid. After sitting for 30 minutes the bright white solid was collected by suction filtration and washed with additional dichloromethane to give N-(4-(2-acetamidopyridin-4-yloxy)-2,5-difluorophenyl)-N′-phenylcyclopropane-1,1-dicarboxamide (0.099 g, 58% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.98 (s, 1H), 10.59 (s, 1H), 9.78 (s, 1H), 8.19 (d, 1H), 8.07 (dd, 1H), 7.65 (d, 1H), 7.55 (m, 3H), 7.32 (m, 2H), 7.09 (t, 1H), 6.71 (dd, 1H), 2.02 (s, 3H), 1.63 (m, 2H), 1.57 (m, 2H); MS (ESI) m/z: 467.2 (M+H+).

Provenance & Evidence