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

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A microwave vial was charged with N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (INTERMEDIATE M, 0.150 g, 0.359 mmol), xantphos (0.042 g, 0.072 mmol), 2-bromo-5-(trifluoromethyl)benzonitrile (Apollo Scientific) (0.135 g, 0.539 mmol), Pd2(dba)3 (0.033 g, 0.036 mmol) and sodium tert-butoxide (0.069 g, 0.719 mmol). The mixture was diluted with toluene (3.59 mL), purged with nitrogen, and heated at 130° C. in the microwave for 1.5 h. After cooling to rt, trifluoroacetic acid (0.554 mL, 7.19 mmol) was carefully added and the reaction was stirred for 1 h. The reaction mixture was diluted with water, and washed with DCM (×2). organics were dried via phase separator, and concentrated under a vacuum. The material was then purified via reverse-phase preparative HPLC, 0.1% TFA in CH3CN/H2O, gradient 25% to 90% over 25 min to provide 4-(2-cyano-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (0.045 g, 0.096 mmol) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.82-3.91 (m, 2 H) 4.28-4.39 (m, 2 H) 6.76-6.85 (m, 2 H) 7.18 (dd, J=8.56, 2.10 Hz, 1 H) 7.21-7.28 (m, 2 H) 7.71 (d, J=8.70 Hz, 1 H) 8.06 (dd, J=8.71, 2.15 Hz, 1 H) 8.40 (d, J=1.27 Hz, 1 H) 12.66 (br. s., 1 H). m/z (ESI) 467.0 (M+H)+.

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