Potassium Carbonate → 5-(2-cyano-4-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide

Participants

Reaction Conditions

Reaction Steps

A pressure vessel was charged with 5-bromo-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide (Intermediate D) (150 mg, 0.288 mmol), potassium carbonate (199 mg, 1.441 mmol), (2-cyano-4-(trifluoromethyl)phenyl)boronic acid (124 mg, 0.576 mmol), tetrakis(triphenylphosphine)palladium(0) (33.3 mg, 0.029 mmol), dioxane (1922 μl) and water (961 μl). The reaction was heated in a microwave to 100° C. for 60 min. Additional (2-cyano-4-(trifluoromethyl)phenyl)boronic acid (124 mg, 0.576 mmol) and tetrakis(triphenylphosphine)palladium(0) (33.3 mg, 0.029 mmol) were added and the resulting mixture was heated in a microwave at 100° C. for an additional hour. After heating the mixture was allowed to cool to room temperature, the organic layer was separated and the organic layer was concentrated. The resulting product was purified by MPLC (40 g silica gel column, eluting with 0% to 50% EtOAc in heptane) to afford a white solid that was further purified by reverse phase HPLC (Column: Xbridge 19×100 mm, 5 μm, Waters, Milford, Mass., Flow rate: 40 mL/min, Mobile phase: 0.1% NH4OH in ACN and water). The fractions containing product were dried under a vacuum to afford 5-(2-cyano-4-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide (2.1 mg, 0.004 mmol) as a white solid. 1H NMR (500 MHz, DMSO-d6) δ ppm 7.58 (d, J=8.76 Hz, 1H) 7.69-7.74 (m, 1H) 7.75-7.83 (m, 2H) 7.87 (d, J=8.01 Hz, 1H) 8.16-8.24 (m, 2H) 8.34 (d, J=8.34 Hz, 1H) 8.52-8.57 (m, 2H); m/z (ESI) 461.0 (M+H)+.

Provenance & Evidence