反応 #560

ord-02be984aa68b424aad9a285d9b990afb

溶媒

反応条件

温度
100°CELSIUS

実験手順

diacetoxypalladium (1.511 mg, 6.73 µmol) was added to a stirred mixture of N,N-dimethyl-2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxamide (50 mg, 0.13 mmol), biphenyl-2-yldicyclohexylphosphine (4.72 mg, 0.01 mmol), 1-bromo-4-fluorobenzene (0.018 ml, 0.17 mmol) and cesium carbonate (65.8 mg, 0.20 mmol) dissolved in 1,4-dioxane (1.5 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 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 8-(1-(4-fluorophenyl)pyrrolidin-2-yl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (10.00 mg, 15.96 %) as a gum.

出典

750 AstraZeneca ELN dataset