Hydrazine hydrate (1:1) → 6-Fluoro-3-(2-fluorobenzyl)-1H-pyrazolo[4,3-b]pyridine

HRID 626614Notes

Reaction equation

HRID 626614 reaction equation
F[C:2]1[C:3]([C:9](=O)[CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[F:17])=[N:4][CH:5]=[C:6]([F:8])[CH:7]=1.O.[NH2:20][NH2:21]>N1C=CC=CC=1.CN(C)C1C=CN=CC=1.C(OCC)(=O)C>[F:8][C:6]1[CH:7]=[C:2]2[NH:21][N:20]=[C:9]([CH2:10][C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[F:17])[C:3]2=[N:4][CH:5]=1

Participants

6

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 666355431-(3,5-Difluoropyridin-2-yl)-2-(2-fluorophenyl)ethanone

Product 1

HCID 1785059746-Fluoro-3-(2-fluorobenzyl)-1H-pyrazolo[4,3-b]pyridine

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Procedure

9.07 g (32.4 mmol) of the compound from example 3A were initially charged in pyridine (84 ml). Subsequently, 8.10 g (162 mmol) of hydrazine hydrate and 19.8 mg (0.162 mmol) of 4-dimethylaminopyridine were added, and the mixture was heated at reflux for 30 min. The reaction mixture was diluted with ethyl acetate at RT and washed four times with 10% strength aqueous citric acid solution. The organic phase was subsequently washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated. MTBE was added to the residue and the solids were filtered off. The latter were dried under high vacuum and gave 1.79 g (79% pure, 18% of theory) of the title compound. The filtrate was concentrated and gave a further 4.86 g (61% pure, 37% of theory) of the title compound. The two fractions were combined and reacted without further purification.

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 30 min
  3. washwashed four times with 10% strength aqueous citric acid solution
  4. washThe organic phase was subsequently washed with saturated aqueous sodium chloride solution
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. additionMTBE was added to the residue
  9. filtrationthe solids were filtered off
  10. customThe latter were dried under high vacuum

Sources & evidence

ORD record
ord-5a0e557efe714838b14dabe8cef22d01
Source dataset
uspto-grants-2016_04
Patent number
US09309239B2

Reaction notes

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