Trifluoroacetic acid → ethyl 5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo(3,4-b)pyridine-3-carboxylate

HRID 536479Notes

Reaction equation

HRID 536479 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:10]=[C:9]([NH2:11])[N:8]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[F:19])[N:7]=1)=[O:5])[CH3:2].CN(C)[CH:22]=[C:23]([F:26])[CH:24]=O.FC(F)(F)C(O)=O>O1CCOCC1>[CH2:1]([O:3][C:4]([C:6]1[C:10]2[C:9](=[N:11][CH:22]=[C:23]([F:26])[CH:24]=2)[N:8]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[F:19])[N:7]=1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 11391384ethyl 5-amino-1-(2-fluorobenzyl)-1H-pyrazole-3-carboxylateHCID 54236093(2z)-3-(Dimethylamino)-2-fluoroacrylaldehyde

Product 1

HCID 56849011ethyl 5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo(3,4-b)pyridine-3-carboxylate

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

13.487 g (51.228 mmol) of ethyl-5-amino-1-(2-fluorobenzyl)-1H-pyrazole-3-carboxylate (preparation described for example 20A in WO 00/06569) was put in 300 ml dioxane and 6 g (51.228 mmol) of 3-(dimethylamino)-2-fluoroacrylaldehyde (preparation described in Justus Liebigs Annalen der Chemie 1970; 99-107) was added at RT. Then 4.736 ml (61.473 mmol) of trifluoroacetic acid was added and the mixture was heated under reflux for 3 days, with stirring. After cooling, it was concentrated by vacuum evaporation and water and ethyl acetate were added to the residue. The phases were separated and the organic phase was washed twice with water. The combined aqueous phases were then extracted twice with ethyl acetate. The combined organic phases were dried over sodium sulphate, filtered and concentrated by vacuum evaporation. The residue (22 g) was then purified by silica gel chromatography (solvent: dichloromethane). 5.67 g (35% of theor.) of the title compound was obtained.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 3 days
  3. temperatureAfter cooling
  4. concentrationit was concentrated by vacuum evaporation and water and ethyl acetate
  5. additionwere added to the residue
  6. customThe phases were separated
  7. washthe organic phase was washed twice with water
  8. extractionThe combined aqueous phases were then extracted twice with ethyl acetate
  9. dry with materialThe combined organic phases were dried over sodium sulphate
  10. filtrationfiltered
  11. concentrationconcentrated by vacuum evaporation
  12. customThe residue (22 g) was then purified by silica gel chromatography (solvent: dichloromethane)

Sources & evidence

ORD record
ord-4a647322b32d4a0b908529d9dc71be19
Source dataset
uspto-grants-2014_10
Patent number
US08859569B2

Reaction notes

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