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0 °C

In a 5 mL microwave vial, 2-((4,6-difluoro-1H-indol-3-yl)sulfonyl)-N-(5-methylisoxazol-3-yl)acetamide (62.0 mg, 0.174 mmol) from Step C was dissolved in DMF (3 mL) and cooled to 0° C. Sodium hydride (60% by weight, 8.0 mg, 0.35 mmol) was then added in one portion and the reaction mixture was vigorously stirred at 0° C. for 15 minutes. 3-bromo-benzylbromide (44.0 mg, 0.174 mmol) was added in one portion and the reaction mixture was stirred while being allowed to warm to ambient temperature over 3 hours. The reaction mixture was quenched with water (2 mL) and the solution was extracted with ethyl acetate (3×4 mL). The organics were combined, dried over magnesium sulfate, and concentrated in vacuo to give an oily residue which was purified on a silica gel column (0-50% ethyl acetate:hexanes over 19 min) to yield the title compound (45 mg, 0.09 mmol, 50% yield). LCMS>98% 220 nm, RT=0.84 min, m/z=524 ([79Br]m+1), 526 ([81Br]m+1). 1H NMR (400 MHz, DMSOD6) 11.32 (s, 1H), 8.39 (s, 1H), 7.59 (s, 1H), 7.52 (m, 2H), 7.29 (t, J=7.6 Hz, 1H), 7.17-7.24 (m, 2H), 6.52 (s, 1H), 5.53 (s, 2H), 4.47 (s, 2H), 2.36 (s, 3H).

1. stirringthe reaction mixture was stirred
2. temperatureto warm to ambient temperature over 3 hours
3. customThe reaction mixture was quenched with water (2 mL)
4. extractionthe solution was extracted with ethyl acetate (3×4 mL)
5. dry with materialdried over magnesium sulfate
6. concentrationconcentrated in vacuo
7. customto give an oily residue which
8. customwas purified on a silica gel column (0-50% ethyl acetate:hexanes over 19 min)