Reaction Steps
A round-bottom flask was charged with perfluorophenyl 5-(pyrrolidin-2-yl)naphthalene-2-sulfonate 2,2,2-trifluoroacetate (104.73 mg, 0.188 mmol), N-(2,4-dimethoxybenzyl)-1,2,4-thiadiazol-5-amine (56.7 mg, 0.225 mmol), and THF (1879 μl) to give a clear solution. The flask was cooled in a dry ice-acetone bath for 10 min, then lithium tert-butoxide (Sigma-Aldrich, St. Louis, Mo., 1M in hexane) (413 μl, 0.413 mmol) was added dropwise. After 35 min, the flask was submerged in an ice-bath for 2 h. The mixture was diluted with saturated aq ammonium chloride, then extracted with EtOAC (3×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (12-g, 0 to 10% MeOH/DCM) to give N-(2,4-dimethoxybenzyl)-5-(pyrrolidin-2-yl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide (61.5 mg, 0.120 mmol, 64.1% yield) as a white foam: 1H NMR (400 MHz, DMSO-d6) δ ppm=8.55 (d, J=2.2 Hz, 1H), 8.41-8.33 (m, 2H), 8.01 (dd, J=7.7, 19.2 Hz, 2H), 7.78 (dd, J=2.2, 9.1 Hz, 1H), 7.68-7.61 (m, 1H), 7.03-6.95 (m, 1H), 6.36 (qd, J=2.3, 4.5 Hz, 2H), 5.18 (s, 2H), 4.77 (t, J=7.4 Hz, 1H), 3.67 (s, 3H), 3.63 (s, 3H), 3.12-2.95 (m, 2H), 2.40-2.30 (m, 1H), 1.83-1.72 (m, 2H), 1.51-1.40 (m, 1H); m/z (ESI) 511.4 (M+H)+.
