反应详情

温度

0 °C

A flask containing thiazol-5-amine hydrochloride (0.093 g, 0.684 mmol), 4-(2-bromo-4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonyl chloride (INTERMEDIATE C, 0.284 g, 0.622 mmol), and THF (4.15 mL) was cooled to 0° C. LHMDS (1.0 M in THF) (1.866 mL, 1.866 mmol) was added dropwise and the reaction was stirred for 5 minutes at 0° C. The reaction was quenched with saturated ammonium chloride solution, diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were dried with sodium sulfate, filtered, and concentrated. The material was purified via silica gel column chromatography (40 g, gradient elution 0 to 100% EtOAc:Heptane) to afford 4-(2-bromo-4-(trifluoromethyl)phenyl)-N-(thiazol-5-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (0.083 g, 0.160 mmol) as an orange oily solid. 1H NMR (400 MHz, DMSO-d6) δ=10.66 (s, 1 H), 8.69 (d, J=0.9 Hz, 1 H), 8.21 (d, J=1.6 Hz, 1 H), 7.91 (dd, J=1.5, 8.3 Hz, 1 H), 7.75 (d, J=7.8 Hz, 1 H), 7.35 (d, J=0.9 Hz, 1 H), 7.12 (d, J=2.2 Hz, 1 H), 7.05 (dd, J=2.2, 8.6 Hz, 1 H), 6.24 (d, J=8.6 Hz, 1 H), 4.37 (d, J=17.2 Hz, 2 H), 3.85-3.63 (m, 2 H). m/z (ESI) 520.2 (M+H)+.

1. customThe reaction was quenched with saturated ammonium chloride solution
2. additiondiluted with ethyl acetate
3. washwashed with water
4. extractionThe aqueous layer was extracted with ethyl acetate
5. dry with materialthe combined organic layers were dried with sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. customThe material was purified via silica gel column chromatography (40 g, gradient elution 0 to 100% EtOAc:Heptane)