Hydrochloric Acid → 4-[5-(4-Chlorophenyl)-3-(3-methoxyphenyl)thiomethyl-1h-pyrazol-1-yl]benzenesulfonamide

Participants

Reaction Steps

4-[5-(4-Chlorophenyl)-3-hydroxymethyl)-1H-pyrazol-1-yl]benzenesulfonamide from Step 3 (500 mg, 1.374 mmol) was dissolved in anhydrous THF (30 mL). Triethylamine (0.385 mL, 2.749 mmol) and methanesulfonyl chloride (0.16 mL, 2.062 mmol) were added sequentially, and the cloudy suspension was stirred at room temperature for 0.5 hour. The reaction was diluted with ethyl acetate (35 mL) and washed with aqueous HCl (1N, 50 mL). The organic solution was dried over anhydrous MgSO4 and filtered, then the solvent was evaporated under reduced pressure to yield a crude oil. The oil was dissolved in anhydrous THF (10 mL). 3-Methoxythiophenol (0.205 mL, 1.649 mmol) was dissolved in anhydrous THF. Sodium hydride (95%, 42 mg, 1.649 mmol) was added, and the resulting frothy suspension was stirred at room temperature for 20 minutes, forming a clear, colorless solution. The solution of the mesylate prepared above was added, then the reaction was warmed to 40° C. and held for 16 hours. The reaction was cooled to room temperature then 1N HCl (30 mL) was added. After stirring an additional 0.5 hour, the system was extracted with ethyl acetate (2×40 mL). The combined organic solution was sequentially washed with 1 N HCl (40 mL), saturated aqueous NaHCO3 (2×40 mL), 50% saturated NaCl (2×40 mL), and brine (40 mL), then dried over anhydrous MgSO4 and filtered. The solvents were evaporated under reduced pressure to yield an oil. The oil was purified by flash chromatography over silica gel eluting with 40% ethyl acetate in hexane to yield 4-[5-(4-chlorophenyl)-3-(3-methoxyphenyl)thiomethyl-1H-pyrazol-1-yl]benzenesulfonamide (273 mg, 41%) as a foam: Mass Spectrum: 486 (MH+). High resolution mass spectrum Calc'd. for C23H20N3O3ClS2: 486.0713. Found: 486.0757. Anal. Calc'd. for C23H20N3O3ClS2: C, 56.84; H, 4.15; N, 8.65; Cl, 7.29; S, 13.19. Found: C, 56.56; H, 4.22; N, 8.61; Cl, 7.41; S, 13.00.

Provenance & Evidence