CN(C)C(=O)c1cc(C2CCCN2)c2oc(N3CCOCC3)cc(=O)c2c1.Fc1ccc(Br)cc1>C1COCCO1.CC(=O)O.CC(=O)O.O=C([O-])[O-].[Cs+].[Cs+].[Pd].c1ccc(-c2ccccc2P(C2CCCCC2)C2CCCCC2)cc1>CN(C)C(=O)c1cc(C2CCCN2c2ccc(F)cc2)c2oc(N3CCOCC3)cc(=O)c2c1diacetoxypalladium (7.56 mg, 0.03 mmol) was added to a stirred mixture of N,N-dimethyl-2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxamide (250 mg, 0.67 mmol), biphenyl-2-yldicyclohexylphosphine (23.59 mg, 0.07 mmol), 1-bromo-4-fluorobenzene (0.092 ml, 0.84 mmol) and cesium carbonate (329 mg, 1.01 mmol) dissolved in 1,4-dioxane (5 ml). The resulting suspension was degased with argon and then stirred at 100 °C for 15 hours. The reaction mixture was allowed to cool to room temperature and concentrated. The crude product was dissolved in 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 8-(1-(4-fluorophenyl)pyrrolidin-2-yl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (155 mg, 49.5 %) as a gum 200mg (155mg from EN05368-13 and 45mg from EN04870-97) was sent to the collection and purified by chiral separation.
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