Water → 4-(2-cyano-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-3-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)-3-methyl-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (900 mg, 2.08 mmol) and 2-fluoro-5-(trifluoromethyl)benzonitrile (546 mg, 2.49 mmol, Alfa Aesar) in dimethylformamide (20 mL) was added Cs2CO3 (1.35 g, 4.16 mmol, GLR) and the mixture was heated at 90° C. for 3 h. The reaction mixture was cooled to room temperature and water (200 mL) was added. The aqueous layer was extracted with ethyl acetate (2×100 mL). The combined organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to obtain the crude material which was further purified by column chromatography (silica gel 100-200 mesh and 0-3% methanol in dichloromethane) to obtain 4-(2-cyano-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-3-methyl-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (700 mg, 56%) as off white solid. 1H NMR (400 MHz, DMSO) δ 8.50 (s, 1H), 8.17 (d, J=8.7 Hz, 1H), 7.77 (d, J=8.6 Hz, 1H), 7.44 (d, J=3.6 Hz, 1H), 7.35 (d, J=3.6 Hz, 1H), 7.30-7.12 (m, 4H), 6.85 (d, J=8.7 Hz, 2H), 6.55 (d, J=8.6 Hz, 1H), 5.02 (s, 2H), 4.23 (m, 2H), 4.19-4.06 (m, 1H), 3.70 (s, 3H), 1.21-1.09 (m, 3H); MS (ESI, positive ion) m/z 601.1 (M+H).

Provenance & Evidence