A vial was charged with N-(2,4-dimethoxybenzyl)-5-(pyrrolidin-2-yl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide (INTERMEDIATE KK) (34.01 mg, 0.067 mmol), chloro(2-dicyclohexylphosphino-2′,6′-di-1-propoxy-1,1′-biphenyl)[2-(2-aminoethylphenyl)]palladium(II), methyl-t-butylether adduct (Strem Chemical, Newburyport, Mass., 2.72 mg, 3.33 mmol), and cesium carbonate (65.1 mg, 0.200 mmol). The vial was flushed with Ar (g), then toluene (0.3 mL) and 2-bromopyridine (19.05 μl, 0.200 mmol) were added. The vial was sealed and placed in a 100° C. heating bath. After 4 h, an additional portion of catalyst (about 3 mg) was added, and the vial was heated for an additional 16 h. Additional portions of catalyst (6 mg) and cesium carbonate (about 55 mg) were added, and the vial was returned to the heat for 5 h. The mixture was cooled to room temperature, diluted with EtOAc, and filtered through diatomaceous earth. The filtrate was concentrated. The residue was purified by chromatography on silica gel (12-g column, 0 to 10% MeOH/DCM) to give 5-(1-(pyridin-2-yl)pyrrolidin-2-yl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide (9.7 mg, 0.022 mmol, 33.3% yield) as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm=8.54 (d, J=2.0 Hz, 1H), 8.45 (s, 1H), 8.38 (d, J=9.2 Hz, 1H), 8.12 (d, J=8.2 Hz, 1H), 8.02-7.88 (m, 2H), 7.72 (br. s., 1H), 7.56-7.48 (m, 1H), 7.33 (d, J=6.9 Hz, 1H), 6.79 (t, J=6.4 Hz, 1H), 6.61 (br. s., 1H), 5.91 (d, J=7.8 Hz, 1H), 4.04 (t, J=8.6 Hz, 1H), 3.77-3.62 (m, 1H), 2.71-2.59 (m, 1H), 2.17-2.05 (m, 1H), 2.01-1.84 (m, 2H); m/z (ESI) 438.4 (M+H)+.
