反应详情

4-[5-(4-Chlorophenyl)-3-(hydroxymethyl)-1H-pyrazol-1-yl]benzenesulfonamide (Example 1 Step 4) (3.0 g, 8.2 mmol) was dissolved in 100 mL of dry tetrahydrofuran and treated with para-toluenesulfonyl chloride (1.56 g, 8.2 mmol), lithium chloride (350 mg, 8.2 mmol), and triethylamine (830 mg, 8.2 mmol). The solution was warmed to reflux for 16 hours and diluted with 100 mL of ethyl acetate. The solution was washed with 1 N hydrochloric acid, saturated aqueous NaHCO3, and water, dried over anhydrous MgSO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography over silica gel eluting with 1:1 (v:v) hexane/ethyl acetate. The appropriate fractions were combined and concentrated and the residue crystallized from ethanol/water to give pure 4-[5-(4-chlorophenyl)-3-chloromethyl-1H-pyrazol-1-yl]benzenesulfonamide as a white solid (2.51 g, 80%): mp 198-201° C. Anal. Calc'd. for C16H13N3S1O2Cl2: C, 50.27; H, 3.43; N, 10.99. Found: C, 50.34; H, 3.43; N, 10.96.

1. temperatureThe solution was warmed
2. temperatureto reflux for 16 hours
3. washThe solution was washed with 1 N hydrochloric acid, saturated aqueous NaHCO3, and water
4. dry with materialdried over anhydrous MgSO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe residue was purified by flash chromatography over silica gel eluting with 1:1 (v:v) hexane/ethyl acetate
8. concentrationconcentrated
9. customthe residue crystallized from ethanol/water