反应详情

温度

23 °C

2-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate(V) (HATU; Aldrich; 5.36 g, 14.10 mmol) was added to a mixture of 2-amino-3-bromo-4-fluorobenzoic acid (Example 719; 3.00 g, 12.82 mmol), ethylamine (2.0 M in MeOH; Aldrich; 7.05 mL, 14.10 mmol), and TEA (2.68 mL, 19.23 mmol) in a mixture of DMF (10 mL) and DCM (10.00 mL), and the resulting solution was stirred at 23° C. for 17 h. The reaction mixture was then diluted with DCM (100 mL), and the resulting solution was sequentially washed with water (2×80 mL), 0.5 N aqueous NaOH (50 mL), and brine (50 mL), then concentrated in vacuo. The residue was chromatographically purified (silica gel, 0-60% EtOAc/hexanes) to yield 2-amino-3-bromo-N-ethyl-4-fluorobenzamide (2.59 g, 9.92 mmol, 77% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.39 (1H, t, J=4.5 Hz), 7.59 (1H, dd, J=8.8, 6.3 Hz), 6.86 (2H, br. s.), 6.57 (1H, t, J=8.5 Hz), 3.20-3.29 (2H, m), 1.11 (3H, t, J=7.2 Hz). 19F NMR (376 MHz, DMSO-d6) δ ppm −101.26 (1F, s). m/z (ESI, +ve) 260.9/262.9 (M+H)+.

1. washthe resulting solution was sequentially washed with water (2×80 mL), 0.5 N aqueous NaOH (50 mL), and brine (50 mL)
2. concentrationconcentrated in vacuo
3. customThe residue was chromatographically purified (silica gel, 0-60% EtOAc/hexanes)