Methyl bromoacetate → 1-[(4-Methoxy)phenyl]-3-[(methoxycarbonyl)methylamino]-1H-pyrazole

HRID 394807Notes

Reaction equation

HRID 394807 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH:13]=[CH:12][C:11]([NH:14][C:15](OC)=O)=[N:10]2)=[CH:5][CH:4]=1.C(=O)(O)[O-].[Na+].BrC[C:26]([O:28][CH3:29])=[O:27]>CN(C=O)C.C(OCC)(=O)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([N:9]2[CH:13]=[CH:12][C:11]([NH:14][CH2:15][C:26]([O:28][CH3:29])=[O:27])=[N:10]2)=[CH:7][CH:8]=1

Participants

6

Reactant 3

HCID 60984Methyl bromoacetate2×HCID 516892Sodium Bicarbonate2×HCID 543443991-[(4-Methoxy)phenyl]-3-[(methoxycarbonyl)amino]-1H-pyrazole

Product 1

HCID 865879801-[(4-Methoxy)phenyl]-3-[(methoxycarbonyl)methylamino]-1H-pyrazoleYield 89.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of 1-[(4-methoxy)phenyl]-3-amino-1H-pyrazole-5-[(2′-tert-butylaminosulfonyl-[1,1′]-biphen-4-yl)carboxyamide (1.0 g, 1.92 mmol) in 10 mL of DMF was added sodium bicarbonate (0.24 g, 2.88 mmol) and methyl bromoacetate (0.22 mL, 2.30 mmol) The resulting mixture was stirred at 85° C. for 16 h. The reaction was not complete so additional portions of sodium bicarbonate (0.48 g, 5.76 mmol) and methyl bromoacetate (0.22 mL, 2.30 mmol) were added and the reaction was stirred at 95° C. for 6 h longer. The reaction was cooled to ambient temperature and was diluted with ethyl acetate. The organics were washed with brine, dried (MgSO4) and concentrated in vacuo. The residue was dissolved in 5 mL of trifluoroacetic acid and was stirred at reflux for 20 min and then was cooled to ambient temperature and concentrated in vacuo. The residue was purified by prep HPLC (C18 reverse phase column, elution with a H2O/CH3CN gradient with 0.5% TFA) and lyophilized to afford 450 mg (44%) of the title compound as a white powder. LRMS (ES+): 536.0 (M+H)+.

Workup

  1. additionwere added
  2. stirringthe reaction was stirred at 95° C. for 6 h longer
  3. temperatureThe reaction was cooled to ambient temperature
  4. washThe organics were washed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residue was dissolved in 5 mL of trifluoroacetic acid
  8. stirringwas stirred
  9. temperatureat reflux for 20 min
  10. temperaturewas cooled to ambient temperature
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by prep HPLC (
  13. washC18 reverse phase column, elution with a H2O/CH3CN gradient with 0.5% TFA) and

Sources & evidence

ORD record
ord-035d58402bef4869b209a771736a4283
Source dataset
uspto-grants-2003_08
Patent number
US06602895B2

Reaction notes

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