Acetamide → HCID 54576082, compound

Participants

Reaction Conditions

Reaction Steps

N-(5-cloro-4-(2-chloropyridin-4-yloxy)-2-fluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (0.200 g, 0.418 mmol), acetamide (0.124 g, 2.091 mmol), cesium carbonate (0.136 g, 0.418 mmol), and xantphos (0.017 g, 0.029 mmol) were dissolved in dry dioxane (3 mL) in a 25 mL round bottom flask. Argon was bubbled through the reaction mixture for 5 minutes, and then palladium acetate (4.69 mg, 0.021 mmol) was added. The mixture was again degassed for five minutes, and then the reaction flask was fitted with a reflux condenser. The system was flushed with argon and then heated at 100° C. under a balloon of argon for 3 hours. The reaction mixture was cooled to room temperature and diluted with water (30 mL) and a 4:1 mixture of ethyl acetate and THF (150 mL). The layers were separated, and the aqueous layer was washed with additional ethyl acetate/THF solution. The organic layers were combined and concentrated to yield a sticky orange oil. Upon addition of methanol (3 mL) a fine cream-colored precipitate formed, which was collected by suction filtration and washed with a small portion of dichloromethane to yield N-(4-(2-acetamidopyridin-4-yloxy)-5-chloro-2-fluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (0.100 g, 47.7% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.91 (s, 1H), 10.58 (s, 1H), 9.83 (s, 1H), 8.23 (d, 1H), 8.18 (d, 1H), 7.58 (m, 4H), 7.15 (m, 2H), 6.65 (dd, 1H), 2.02 (s, 3H), 1.61 (m, 2H), 1.56 (m, 2H); MS (ESI) m/z: 501.1 (M+H+).

Provenance & Evidence