Cesium carbonate → 6-chloro-4-(2-cyano-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

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Reaktionsschritte

A 150-mL pressure vessel was charged with 6-chloro-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (2.32 g, 5.13 mmol), 2-bromo-5-(trifluoromethyl)benzonitrile (2.57 g, 10.27 mmol), Xantphos (0.594 g, 1.027 mmol), Pd2(dba)3 (0.470 g, 0.513 mmol), and cesium carbonate (5.02 g, 15.40 mmol). The vessel was flushed with Ar (g), then 1,4-dioxane (51.3 ml) was added. The vessel was sealed and placed in a 100° C. heating bath for 16 h. The mixture was cooled to room temperature, diluted with water, and extracted with EtOAc (3×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The crude product was purified by chromatography on silica gel (50-g Redi-Sep Gold column, 25-g silica gel loading column, 25-75% EtOAc/Heptane) to give 6-chloro-4-(2-cyano-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ=8.46 (d, J=2.1 Hz, 1 H), 8.15 (dd, J=1.8, 8.7 Hz, 1 H), 7.81 (d, J=8.5 Hz, 1 H), 7.50 (s, 1 H), 7.45 (d, J=3.6 Hz, 1 H), 7.32 (d, J=3.5 Hz, 1 H), 7.28-7.21 (m, 2 H), 6.90-6.78 (m, 3 H), 5.17 (s, 2 H), 4.40-4.34 (m, 2 H), 3.91-3.85 (m, 2 H), 3.71 (s, 3 H); m/z (ESI) 621.0 (M+H)+.

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