4-Toluenesulfonyl chloride → 4-(5-(4-chlorophenyl)-3-chloromethyl-1H-pyrazol-1-yl]benzenesulfonamide

HRID 1814024Notes

Reaction equation

HRID 1814024 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([C:13]3[CH:18]=[CH:17][C:16]([S:19]([NH2:22])(=[O:21])=[O:20])=[CH:15][CH:14]=3)[N:11]=[C:10]([CH2:23]O)[CH:9]=2)=[CH:4][CH:3]=1.C1(C)C=CC(S([Cl:34])(=O)=O)=CC=1.[Cl-].[Li+].C(N(CC)CC)C>O1CCCC1.C(OCC)(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([C:13]3[CH:18]=[CH:17][C:16]([S:19]([NH2:22])(=[O:21])=[O:20])=[CH:15][CH:14]=3)[N:11]=[C:10]([CH2:23][Cl:34])[CH:9]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 433294Lithium ChlorideHCID 99471654-(5-(4-chlorophenyl)-3-hydroxymethyl-1H-pyrazol-1-yl]benzenesulfonamide

Product 1

HCID 99701264-(5-(4-chlorophenyl)-3-chloromethyl-1H-pyrazol-1-yl]benzenesulfonamideYield 80.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-3a1862222228470894ccd5f3fbf925b4
Source dataset
uspto-grants-2005_04
Patent number
US06875785B2

Reaction notes

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