Triethylamine → 1-[(4-methoxy)phenyl]-3-(ethoxycarbonyl)-1H-pyrazole

HRID 394801Notes

Reaction equation

HRID 394801 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13](C(O)=O)=[CH:12][C:11]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[N:10]2)=[CH:5][CH:4]=1.C(N(CC)CC)C>S(Cl)(Cl)=O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([N:9]2[CH:13]=[CH:12][C:11]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[N:10]2)=[CH:7][CH:8]=1

Participants

4

Reactant 2

HCID 8471TriethylamineHCID 544762241-[(4-Methoxy)phenyl]-3-(ethoxycarbonyl)pyrazole-5-carboxylic acid

Product 1

HCID 143726701-[(4-methoxy)phenyl]-3-(ethoxycarbonyl)-1H-pyrazoleYield 91.5%

Reagents, catalysts & solvents 1

HCID 24386Thionyl ChlorideSolvent

Procedure

A solution of 1-[(4-methoxy)phenyl]-3-(ethoxycarbonyl)pyrazole-5-carboxylic acid (3.2 g, 11.1 mmol) in 20 mL of thionyl chloride was stirred at 80° C. for 1 h. The volatiles were then removed and the residue was azeotroped with 20 mL of toluene and dried in vacuo. The residue was dissolved in 50 mL of methylene chloride and then there was added triethylamine (4.6 mL, 33.3 mmol) and 4-(N-pyrrolidinocarbonyl)aniline (3.2 mL, 54.3 mmol). The reaction mixture was allowed to stir at ambient temperature for 4 h. The volatiles were removed and the residue was dissolved in ethyl acetate, washed sequentially with 10% aq HCl and brine, dried (MgSO4), filtered through a short pad of silica gel and concentrated to afford 2.5 g (50%) of the title compound. A small portion was further purified by prep HPLC (C18 reverse phase column, elution with a H2O/CH3CN gradient with 0.5% TFA) and lyophilized to afford the title compound as a white powder. LRMS (ES+): 463.1 (M+H)+.

Workup

  1. customThe volatiles were then removed
  2. customthe residue was azeotroped with 20 mL of toluene
  3. customdried in vacuo
  4. dissolutionThe residue was dissolved in 50 mL of methylene chloride
  5. customThe volatiles were removed
  6. dissolutionthe residue was dissolved in ethyl acetate
  7. washwashed sequentially with 10% aq HCl and brine
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered through a short pad of silica gel
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-eb2cb09935d441b39e10170573cef61c
Source dataset
uspto-grants-2003_08
Patent number
US06602895B2

Reaction notes

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