Sodium hydride → 6-(1-Methanesulfonyl-piperidin-4-yloxy)-pyridine-3-sulfonic acid (4-fluoro-phenyl)-isobutyl-amide

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Reaction Steps

To a solution of 1-methanesulfonyl-piperidin-4-ol (86 mg, 482 μmol) in anhydrous THF (5 mL) at room temperature was added NaH (60% dispersion in mineral oil, 21 mg, 526 μmol) and the reaction was stirred at room temperature for 15 minutes. Chloro-pyridine-3-sulfonic acid (4-fluoro-phenyl)-isobutyl-amide (150 mg, 439 μmol) was added and the reaction stirred at room temperature for 45 minutes then heated at 80° C. for 2 hours. Water and saturated NaHCO3 were added and then extracted with EtOAc, washed with brine, dried with Na2SO4 then concentrated and purified by silica gel column chromatography (0-25% EtOAc in cyclohexane) to give the title compound (137 mg). 1H NMR (400 MHz, DMSO): δ 8.30 (dd, J=2.6, 0.67 Hz, 1H), 7.75 (dd, J=8.8, 2.60 Hz, 1H), 7.19-7.20 (m, 4H), 6.97 (dd, J=8.8, 0.7 Hz, 1H), 5.23-5.25 (m, 1H), 3.39 (d, J=8.8 Hz, 4H), 3.13 (ddd, J=12.2, 8.56, 3.46 Hz, 2H), 2.91 (s, 3H), 2.04-2.09 (m, 2H), 1.78-1.80 (m, 2H), 1.44 (dd, J=13.6, 6.9 Hz, 1H), 0.85 (d, J=6.6 Hz, 6H). LCMS (m/z, Method B) ES+ 485.9 [M+1]+.

Provenance & Evidence