反应详情

温度

80 °C

In a 5 mL microwave vial, 2-((1-(3-bromobenzyl)-4,6-difluoro-1H-indol-3-yl)sulfonyl)-N-(5-methyl-isoxazol-3-yl)acetamide (20 mg, 0.38 mmol), prepared in Example 1, was dissolved in DMF (2 mL). PdCl2(PPh3)2 (1.0 mg, 0.001 mmol), 1-Boc-pyrazole-4-boronic acid pinacol ester (20 mg, 0.68 mmol), and 2 N aqueous sodium carbonate (1 mL) were added and stirred at 80° C. overnight. The reaction was cooled to ambient temperature. Water (2 mL) was added and the mixture was extracted with ethyl acetate (2×3 mL). The organics were combined, dried over magnesium sulfate and concentrated in vacuo to give an oily residue which was purified on a Gilson Prep HPLC system (5-95% acetonitrile:water (0.1% TFA) over 6 min) to afford the title compound (4.0 mg, 0.008 mmol, 21% yield) as a white solid. LCMS>98% 220 nm, RT=0.79 min, m/z=512 (m+1). 1H NMR (400 MHz, DMSOD6) 12.97 (s, 1H), 11.33 (s, 1H), 8.38 (s, 1H), 8.16, (s, 1H), 7.91 (s, 1H), 7.61 (s, 1H), 7.49-7.55 (m, 2H), 7.28 (t, J=8.0 Hz, 1H), 7.18 (d, J=10.8 Hz, 1H), 7.00 (d, J=7.6 Hz, 1H), 6.48 (s, 1H), 5.52 (s, 2H), 4.48 (s, 2H), 2.35 (s, 3H).

1. temperatureThe reaction was cooled to ambient temperature
2. extractionthe mixture was extracted with ethyl acetate (2×3 mL)
3. dry with materialdried over magnesium sulfate
4. concentrationconcentrated in vacuo
5. customto give an oily residue which
6. customwas purified on a Gilson Prep HPLC system (5-95% acetonitrile:water (0.1% TFA) over 6 min)