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

Participants

Reaction Conditions

Reaction Steps

To a solution of N-(4-methoxybenzyl)-2-methyl-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (INTERMEDIATE AE) (1.3 g, 3.02 mmol) and 2-fluoro-5-(trifluoromethyl)benzonitrile in DMF (20 ml) was added Cs2CO3 (1.8 g, 5.56 mmol) at 25° C. and the reaction mixture was stirred at 90° C. for 2 h. The reaction mixture was poured into ice water and the resulting mixture was extracted with EtOAc. The layers were separated and the organic layer was washed with water, dried over sodium sulfate and concentrated. The resulting residue was purified by silica gel column chromatography using a gradient of 0-50% EtOAc in hexanes to afford 1.2 g of 4-(2-cyano-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-2-methyl-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide as off white solid in 75% yield. 1H-NMR (400 MHz, DMSO): 6.44 (s, 1H), 8.12 (d, J=8.8 Hz, 1H), 7.76 (d, J=8.4 Hz, 1H), 7.75-7.77 (m, 1H), 7.43-7.44 (m, 1H), 7.19-7.25 (m, 4H), 6.78-6.86 (m, 3H), 5.02 (s, 2H), 4.37-4.42 (m, 1H), 3.89-3.92 (m, 1H), 3.70 (s, 3H), 3.55-3.61 (m, 1H), 1.35 (s, 3H); m/z (ESI, positive ion) 601.0 (M+H)

Provenance & Evidence