Bromobenzene → N,N-dimethyl-2-morpholino-4-oxo-8-(1-phenylpyrrolidin-2-yl)-4H-chromene-6-carboxamide

Participants

Reaction Conditions

Reaction Steps

diacetoxypalladium (3.93 mg, 0.02 mmol) was added to a stirred mixture of N,N-dimethyl-2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxamide (130 mg, 0.35 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (20.25 mg, 0.03 mmol), bromobenzene (0.046 ml, 0.44 mmol) and cesium carbonate (171 mg, 0.52 mmol) dissolved in 1,4-dioxane (4 ml). The resulting suspension was degased with argon and then stirred at 100 °C (18:00) for 15 hours. The reaction mixture was allowed to cool to room temperature, filtered and concentrated in V-10 Evaporator (Biotage) The crude product was dissolved in 2ml of DMA. The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (C-18, 5 microns silica, 30 mm diameter, 150 mm length, flow rate of 60 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 N,N-dimethyl-2-morpholino-4-oxo-8-(1-phenylpyrrolidin-2-yl)-4H-chromene-6-carboxamide (59.0 mg, 37.7 %) as a solid.

Provenance & Evidence