Benzenesulfonamide → HCID 22660778, compound

Participants

Reaction Steps

A suspension of compound 49 (0.060 g, 0.14 mmol) and thionyl chloride (0.051 mL) in benzene (2 mL) was refluxed for 2 h under an argon atmosphere. The reaction mixture was cooled to rt and concentrated on a rotary evaporator. The residue was coevaporated with benzene (2×) to afford the acid chloride as a white solid (0.062 g, 100%). Sodium hydride (0.0101 g, 0.252 mmol, 60% dispersion in oil was added to a solution of phenylsulfonamide (0.0425 g, 0.270 mmol) in dimethylformamide (1 mL) at rt under an argon atmosphere. After 1 h, dichloromethane was added (1 mL), followed by the acid chloride of 49 at 0° C. The reaction was warmed to rt. After 1 h, the reaction was diluted with dichloromethane and quenched with 1 N hydrochloric acid. The aqueous layer was washed with dichloromethane (3×). The combined organic layers were dried (MgSO4) and concentrated on a rotary evaporator. The residue was purified by column chromatography (silica gel, 25% acetone/toluene (v/v)). This material was further purified by reverse phase HPLC (C18 column, water/acetonitrile gradient containing 0.05% trifluoroacetic acid) to afford 55 as a white solid (0.0219 g, 54%). 1H NMR (CDCl3) δ 8.71 (d, 1H, J=1.1 Hz), 8.05 (m, 3H), 7.82 (d, 1H, J=8.8 Hz), 7.69 (d, 2H, J=9.1 Hz), 7.58 (m, 1H), 7.51-7.36 (m, 7H), 7.21 (d, 2H, 8.8 Hz), 5.16 (s, 2H), 4.52 (m, 1H), 2.32 (br m, 2H), 2.01 (br m, 4H), 1.80 (br m, 1H), 1.35 (br m, 3H); ESI-MS m/e 566.4 (M+1); HPLC purity (ELSD)>95%.

Provenance & Evidence