Hydrochloric Acid → 3-Chloro-4-((5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-N-(pyrrolidin-1-ylcarbamoyl)benzenesulfonamide

Participants

Reaction Steps

To a stirred solution of 3-chloro-4-((5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)benzenesulfonamide (76 mg, 0.13 mmol, 1.0 eq) in MeOH (0.5 mL) was added sodium hydroxide (5 mg, 0.13 mmol, 1.0 eq, dissolved in 0.5 mL MeOH). The mixture was stirred at room temperature for 16 h then concentrated in vacuo. The residue was diluted with anhydrous DMF (0.5 mL) and then charged with a solution of phenyl pyrrolidin-1-ylcarbamate (30 mg, 0.14 mmol, 1.1 eq) in 0.5 mL of DMF. Phenyl pyrrolidin-1-ylcarbamate was prepared by treatment of phenychloroformate with 1-aminopyrrolidine. The reaction mixture was then heated at 50° C. overnight. The mixture was cooled, acidified with 1M HCl and extracted with ethyl acetate (3×). The organic layers were washed with brine, dried (magnesium sulfate) and concentrated. Purification by column chromatography (30% methanol/ethyl acetate) provided the title compound (15 mg) as a white foam. 1H NMR (CD2Cl2, 400 MHz): δ 8.98 (br s, 1H), 8.00 (s, 1H), 7.82 (dd, J=8.3, 2.2 Hz, 1H), 7.51 (d, J=8.3 Hz, 1H), 7.27 (d, J=8.3 Hz, 1H), 7.18 (s, 1H), 7.00 (d, J=2.2 Hz, 1H), 6.85-6.78 (m, 4H), 6.32-6.27 (m, 2H), 4.33 (s, 2H), 3.22-3.13 (2H), 2.48-2.38 (m, 2H), 1.86-1.78 (m, 4H), 1.47 (s, 6H); MS (EI) m/z 695 (MH)+.

Provenance & Evidence