Sodium Hydroxide → 5-Amino-3-(4-tolyl)-1-(3-trifluoromethoxyphenyl)pyrazole-4-carboxamide

HRID 582007Notes

Reaction equation

HRID 582007 reaction equation
[OH-].[Na+].Cl.[F:4][C:5]([F:16])([F:15])[O:6][C:7]1[CH:8]=[C:9]([NH:13][NH2:14])[CH:10]=[CH:11][CH:12]=1.[C:17]([C:19](=[C:23](SC)[C:24]1[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=1)[C:20]([NH2:22])=[O:21])#[N:18]>C(O)C>[NH2:18][C:17]1[N:13]([C:9]2[CH:10]=[CH:11][CH:12]=[C:7]([O:6][C:5]([F:15])([F:16])[F:4])[CH:8]=2)[N:14]=[C:23]([C:24]2[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=2)[C:19]=1[C:20]([NH2:22])=[O:21]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 45046393(3-(Trifluoromethoxy)phenyl)hydrazine hydrochlorideHCID 542422372-Cyano-3-methylthio-3-(4-tolyl)acrylamide

Product 1

HCID 545661205-Amino-3-(4-tolyl)-1-(3-trifluoromethoxyphenyl)pyrazole-4-carboxamideYield 42.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Powdered sodium hydroxide (88 mg, 2.2 mmol) was added to a solution of 3-trifluoromethoxyphenyl hydrazine hydrochloride (503 mg, 2.2 mmol) and 2-cyano-3-methylthio-3-(4-tolyl)acrylamide (464 mg, 2.0 mmol) in ethanol (20 ml) and the mixture heated at reflux for 18 h. On cooling, the solvent was removed under reduced pressure and the residue partitioned between water (80 ml) and ethyl acetate (100 ml). The aqueous layer was further extracted with ethyl acetate (2×80 ml) and the combined organic layers washed with brine (100 ml), dried (MgSO4) and concentrated under reduced pressure. The crude product was recrystallised from isopropyl ether-heptane to give the title compound as white needles (320 mg) m.p. 177-179°. δH (CDCl3) 7.70 (1H, m), 7.51 (1H, d, J 8.0 Hz), 7.38 (1H, d, J 8.0 Hz), 7.40 (1H, m), 7.09 (1H, d, J 7.9 Hz), 5.74 (2H, br s), 5.35 (2H, br s) and 2.42 (9H, s).

Workup

  1. temperaturethe mixture heated
  2. temperatureat reflux for 18 h
  3. temperatureOn cooling
  4. customthe solvent was removed under reduced pressure
  5. customthe residue partitioned between water (80 ml) and ethyl acetate (100 ml)
  6. extractionThe aqueous layer was further extracted with ethyl acetate (2×80 ml)
  7. washthe combined organic layers washed with brine (100 ml)
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated under reduced pressure
  10. customThe crude product was recrystallised from isopropyl ether-heptane

Sources & evidence

ORD record
ord-f02fe20915ec4309a734091ec3fedc13
Source dataset
uspto-grants-1999_07
Patent number
US05922741

Reaction notes

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