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

Participants

Reaction Steps

A round-bottom flask was charged with 4-(2-bromo-4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonyl chloride (INTERMEDIATE C, 299.84 mg, 0.657 mmol), thiazol-4-amine (79 mg, 0.788 mmol), and THF (3283 n1) to give a brown mixture. The flask was cooled in an ice-bath for 10 min, then lithium bis(trimethylsilyl)amide (1M in THF) (1379 μl, 1.379 mmol) was added dropwise over 30 s. After 30 min, the cooling bath was removed, and the mixture was allowed to warm to room temperature. The reaction mixture was quenched by the addition of aq. 1N hydrochloric acid and a small amount of brine and extracted with EtOAc (3×, emulsion). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was purified by silica gel chromatography on a 40 g column with 0 to 10% MeOH/DCM. The desired product was repurified again by chromatography on a 40 g silica gel column, this time with 0 to 40% EtOAc/Heptane to give 4-(2-bromo-4-(trifluoromethyl)phenyl)-N-(thiazol-4-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (73.1 mg, 0.140 mmol) as a cream-colored solid. 1H NMR (400 MHz, DMSO-d6) δ=10.88 (s, 1 H), 8.88 (d, J=2.2 Hz, 1 H), 8.20 (d, J=1.5 Hz, 1 H), 7.89 (dd, J=1.6, 8.5 Hz, 1 H), 7.73 (d, J=8.4 Hz, 1 H), 7.25 (d, J=2.2 Hz, 1 H), 7.16 (dd, J=2.2, 8.6 Hz, 1 H), 6.96 (d, J=2.2 Hz, 1 H), 6.22 (d, J=8.6 Hz, 1 H), 4.36 (d, J=15.8 Hz, 2 H), 3.78-3.63 (m, 2 H). m/z (ESI) 520.2 (M+H)+.

Provenance & Evidence