Cesium carbonate → 4-(5-cyano-2-methoxyphenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

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A vial was charged with N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (INTERMEDIate M) (80 mg, 0.192 mmol), 3-bromo-4-methoxybenzonitrile (81 mg, 0.383 mmol), Xantphos (22.17 mg, 0.038 mmol), Pd2(dba)3 (17.55 mg, 0.019 mmol), and cesium carbonate (187 mg, 0.575 mmol). The vessel was flushed with Ar (g), then 1,4-dioxane (1916 μl) was added. The vessel was sealed and placed in a 100° C. heating bath for 20 h. The mixture was filtered through celite with the aid of EtOAc. The filtrate was concentrated, and the residue was dissolved in DCM (1 mL) and TFA (0.5 mL). After 4 h, mixture was diluted with MeOH, then concentrated. The residue was purified by chromatography on silica gel (12-g Redi-Sep Gold column, 0-5% MeOH/DCM). The material this obtained was further purified by chromatography on silica gel (12-g Redi-Sep Gold column, 50-100% EtOAc/Heptane). The resulting solid was taken up in EtOAc, sonicated, and filtered. The collected solid was washed with EtOAc (2×), dried under a stream of N2 (g), then dried under vacuum to give 4-(5-cyano-2-methoxyphenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (58 mg, 0.135 mmol, 70.6% yield) as an off-white solid: 1H NMR (400 MHz, DMSO-d6) δ=12.55 (br. s., 1 H), 7.92-7.77 (m, 2 H), 7.34 (d, J=8.5 Hz, 1 H), 7.22 (d, J=4.5 Hz, 1 H), 7.16-7.06 (m, 2 H), 6.78 (d, J=4.5 Hz, 1 H), 6.21 (d, J=8.4 Hz, 1 H), 4.30 (br. s., 2 H), 3.85 (s, 3 H), 3.63 (br. s., 2 H); m/z (ESI) 429.2 (M+H)+.

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