Cesium carbonate → 5-(2-phenylpyrrolidin-1-yl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide

Participants

Reaction Conditions

Reaction Steps

A vial was charged with 5-bromo-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide (205 mg, 0.394 mmol), Xantphos (45.6 mg, 0.079 mmol), Pd2(dba)3 (36.1 mg, 0.039 mmol), and cesium carbonate (257 mg, 0.788 mmol). The vial was flushed with Ar (g), then toluene (3939 μl) and 2-phenylpyrrolidine (81 μl, 0.551 mmol) were added in sequence. The vial was sealed and heated at 100° C. for 16 h. The reaction mixture was partitioned between EtOAc and water. The layers were separated, and the organic extract was washed with brine. The combined aq. layers were extracted with EtOAc, and the organic layers were combined. The combined solution was washed with brine, dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel with 0 to 50% EtOAc/Heptane to give a clear oil. This material was dissolved in DCM (2 mL) and TFA (1 mL), and the resulting mixture was stirred for 2 h. The mixture was diluted with MeOH, then concentrated. The crude product was purified by chromatography on silica gel with 0 to 5% MeOH/DCM to give 5-(2-phenylpyrrolidin-1-yl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide (76.7 mg, 0.176 mmol) as a light-yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm=8.55-8.46 (m, 2H), 8.34 (d, J=2.1 Hz, 1H), 7.78 (dd, J=2.1, 9.0 Hz, 1H), 7.63 (d, J=8.2 Hz, 1H), 7.43-7.33 (m, 3H), 7.22-7.16 (m, 2H), 7.12-7.06 (m, 2H), 4.82 (dd, J=6.3, 9.1 Hz, 1H), 4.19-4.12 (m, 1H), 3.03 (dt, J=4.5, 8.9 Hz, 1H), 2.47-2.40 (m, 1H), 2.14-2.10 (m, 1H), 2.00-1.79 (m, 2H). m/z (ESI) 437.2 (M+H)+.

Provenance & Evidence