1-Bromo-3,5-difluorobenzene → 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide

Participants

Reaction Conditions

Reaction Steps

diacetoxypalladium (2.90 mg, 0.01 mmol) was added to a stirred mixture of N,N-dimethyl-2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxamide (120 mg, 0.32 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (15.89 mg, 0.03 mmol), 1-bromo-3,5-difluorobenzene (46.5 µl, 0.40 mmol) and cesium carbonate (158 mg, 0.48 mmol) suspended in 1,4-dioxane (3184 µl). The resulting suspension was degased with argon and then stirred at 100 °C for 20 hours. The mixture was evaporated and diluted with DMF. The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (C-18, 5 microns silica, 19 mm diameter, 100 mm length, flow rate of 40 ml / minute) and decreasingly polar mixtures of water (containing 0.2% ammonium carbonate) and acetonitrile as eluent. The fractions containing the desired compound were evaporated to dryness to afford 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (77 mg, 49.3 %) as a beige solid.

Provenance & Evidence