Triethylamine → 1-[(4-Methoxy)phenyl)-3-(methoxycarbonylamino)-5-(methoxycarbonyl)pyrazole

HRID 394804Notes

Reaction equation

HRID 394804 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][C:11](C(O)=O)=[N:10]2)=[CH:5][CH:4]=1.C([N:23](CC)CC)C.Cl[C:29]([O:31][CH2:32]C(C)C)=[O:30].[N-]=[N+]=[N-].[Na+]>CC(C)=O.C(OCC)(=O)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([N:9]2[C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][C:11]([NH:23][C:29]([O:31][CH3:32])=[O:30])=[N:10]2)=[CH:7][CH:8]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 33557Sodium AzideHCID 62365Isobutyl chloroformateHCID 542100671-[(4-Methoxy)phenyl]-5-(methoxycarbonyl)pyrazole-3-carboxylic acid

Product 1

HCID 541498731-[(4-Methoxy)phenyl)-3-(methoxycarbonylamino)-5-(methoxycarbonyl)pyrazoleYield 33.1%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 1-[(4-methoxy)phenyl]-5-(methoxycarbonyl)pyrazole-3-carboxylic acid (3.0 g, 10.9 mmol) in 50 mL of acetone at 0° C. was added triethylamine (1.66 mL, 11.9 mmol) followed by iso-butyl chloroformate (1.14 mL, 11.9 mmol). The resulting was stirred for 30 min whereupon an aqueous solution of sodium azide (2.82 g, 43.4 mmol) was added. The reaction was stirred at 0° C. for 1 h. The reaction was then diluted with ethyl acetate and washed with brine. The organics were dried (MgSO4) and concentrated in vacuo. The residue was dissolved in 50 mL of toluene and stirred at 100° C. for 1 h. The volatiles were removed in vacuo and the residue was dissolved in methanolic sodium methoxide (5 mL of a 25% solution of sodium methoxide in methanol, 21 mmol) and stirred at ambient temperature for 2 h. The reaction was diluted with ethyl acetate, washed with wtaer and brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by flash chromatography (elution with 1:1 hexanes/ethyl acetate) to afford 1.1 g (33%) of the title compound as a solid. LRMS (DCI): 306.3 (M+H)+.

Workup

  1. additionwas added
  2. washwashed with brine
  3. dry with materialThe organics were dried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was dissolved in 50 mL of toluene
  6. stirringstirred at 100° C. for 1 h
  7. customThe volatiles were removed in vacuo
  8. dissolutionthe residue was dissolved in methanolic sodium methoxide (5 mL of a 25% solution of sodium methoxide in methanol, 21 mmol) and
  9. stirringstirred at ambient temperature for 2 h
  10. additionThe reaction was diluted with ethyl acetate
  11. washwashed with wtaer and brine
  12. dry with materialdried (MgSO4)
  13. concentrationconcentrated in vacuo
  14. customThe residue was purified by flash chromatography (elution with 1:1 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-fc496f3ce64f4a4983cd54ce74078ae4
Source dataset
uspto-grants-2003_08
Patent number
US06602895B2

Reaction notes

Loading…