Trifluoroacetic anhydride → HCID 57749303, compound

HRID 1874403Notes

Reaction equation

HRID 1874403 reaction equation
[NH2:1][C:2](=O)[CH2:3][N:4]1[CH:9]([NH:10]S(C2C=CC(C)=CC=2)(=O)=O)[CH:8]=[CH:7][C:6]([O:21][C:22]2[CH:23]=[CH:24][C:25]([F:38])=[C:26]([NH:28][C:29]([C:31]3[N:35]([CH3:36])[N:34]=[C:33]([CH3:37])[CH:32]=3)=[O:30])[CH:27]=2)=[CH:5]1.FC(F)(F)C(OC(=O)C(F)(F)F)=O>ClCCl>[NH2:1][C:2]1[N:10]=[C:9]2[CH:8]=[CH:7][C:6]([O:21][C:22]3[CH:23]=[CH:24][C:25]([F:38])=[C:26]([NH:28][C:29]([C:31]4[N:35]([CH3:36])[N:34]=[C:33]([CH3:37])[CH:32]=4)=[O:30])[CH:27]=3)=[CH:5][N:4]2[CH:3]=1

Participants

4

Reactant 2

HCID 9845Trifluoroacetic anhydrideHCID 68990672HCID 68990672, compound

Product 1

HCID 57749303HCID 57749303, compoundYield 18.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of N-{5-[(1-(2-amino-2-oxoethyl)-6-{[(4-methylphenyl)sulfonyl]amino}-1,6-dihydropyridin-3-yl)oxy]-2-fluorophenyl}-1,3-dimethyl-1H-pyrazole-5-carboxamide (5.85 g, 10.6 mmol), trifluoroacetic anhydride (40 mL) and dichloromethane (40 mL) was stirred at room temperature for 6 hr. The reaction solution was concentrated under reduced pressure, ethyl acetate (50 mL) and saturated aqueous sodium hydrogen carbonate solution (50 mL) were added to the residue and the mixture was stirred for 10 min. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and filtrated. The filtrate was concentrated under reduced pressure, 8N aqueous sodium hydroxide solution (15 mL) and ethanol (60 mL) were added to the residue. The mixture was stirred at room temperature for 2 hr and at 60° C. for 2 hr. The reaction mixture was diluted with water and extracted with ethyl acetate/tetrahydrofuran (×3). The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and filtrated. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography (NH silica gel, ethyl acetate) and recrystallized from ethyl acetate-hexane to give the title compound (730 mg, 18%) as a white solid.

Workup

  1. concentrationThe reaction solution was concentrated under reduced pressure, ethyl acetate (50 mL) and saturated aqueous sodium hydrogen carbonate solution (50 mL)
  2. additionwere added to the residue
  3. stirringthe mixture was stirred for 10 min
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltrated
  7. concentrationThe filtrate was concentrated under reduced pressure, 8N aqueous sodium hydroxide solution (15 mL) and ethanol (60 mL)
  8. additionwere added to the residue
  9. stirringThe mixture was stirred at room temperature for 2 hr and at 60° C. for 2 hr
  10. additionThe reaction mixture was diluted with water
  11. extractionextracted with ethyl acetate/tetrahydrofuran (×3)
  12. washThe organic layer was washed with saturated brine
  13. dry with materialdried over anhydrous magnesium sulfate
  14. filtrationfiltrated
  15. concentrationThe filtrate was concentrated under reduced pressure
  16. customthe residue was purified by column chromatography (NH silica gel, ethyl acetate)
  17. customrecrystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-4d7d81918c264c7ca9cfc4785050a69a
Source dataset
uspto-grants-2012_11
Patent number
US08304557B2

Reaction notes

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