反应详情

温度

140 °C

A solution of tris(dibenzylideneacetone)dipalladium(0) (0.337 g, 0.368 mmol) and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.213 g, 0.368 mmol) in n-butanol:dioxane (1:1) (5 mL) was stirred at room temperature for 3 minutes. Then 5-bromo-2-(2,6-difluorophenyl)oxazole-4-carbonitrile (1.50 g, 5.262 mmol), 4-aminobenzoic acid (2.165 g, 15.787 mmol) and cesium carbonate (3.429 g, 10.525 mmol) were added and the mixture heated in the microwave for 3 minutes at 140° C. The reaction was diluted with EtOAc and washed with water. The organic phase was passed through an MP-SH cartridge, dried over MgSO4 and the solvent removed in vacuo. The residue was purified by column chromatography using a 20-45% EtOAc:hexane gradient then further purified by trituration of the solid in DCM:hexane (1:1) to afford 4-(4-cyano-2-(2,6-difluorophenyl)oxazol-5-ylamino)benzoic acid (0.251 g, 0.735 mmol, 14%) as a light yellow solid. 1H NMR (DMSO) δ 7.34 (2H, t), 7.40 (2H, d), 7.66 (1H, m), 7.92 (2H, d), 11.16 (1H, br s), 12.76 (1H, br s). LCMS (3) Rt: 1.53 min; m/z (ES+) 342.

1. washwashed with water
2. dry with materialdried over MgSO4
3. customthe solvent removed in vacuo
4. customThe residue was purified by column chromatography
5. customhexane gradient then further purified by trituration of the solid in DCM:hexane (1:1)