Hydrazine hydrate (1:1) → HCID 72207820, compound
Reaction equation
[F:1][C:2]1([F:11])[CH2:5][CH:4]([C:6](=O)[CH2:7][C:8]#[N:9])[CH2:3]1.O.[NH2:13][NH2:14]>CCO>[F:1][C:2]1([F:11])[CH2:5][CH:4]([C:6]2[NH:14][N:13]=[C:8]([NH2:9])[CH:7]=2)[CH2:3]1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 75 °C
Procedure
To a solution of 3-(3,3-difluorocyclobutyl)-3-oxopropanenitrile (12.5 g, 78.6 mmol) in EtOH (250 mL) was added hydrazine hydrate (5.9 g, 117.9 mmol) and the resulting mixture was stirred at 75° C. overnight. After concentrating the reaction mixture in vacuo, the residue was redissolved in EtOAc (500 mL) and washed with satd. aq. NaHCO3. The aqueous layer was extracted with EtOAc and the combined extracts washed with brine (100 mL), dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by SiO2 chromatography eluting with DCM/MeOH (10:1) to afford 3.46 g (39%) of 5-(3,3-difluoro-cyclobutyl)-1H-pyrazol-3-ylamine as a light yellow solid: 1H NMR (400 MHz, DMSO-do): δ 11.20 (br s, 1H), 5.23 (s, 1H), 4.65 (br s, 2H), 3.16-3.13 (m, 1H), 2.88-2.84 (m, 2H), 2.64-2.57 (m, 2H); MS (ESI+) m/z: 174 [M+1]+.
Workup
- concentrationAfter concentrating the reaction mixture in vacuo
- dissolutionthe residue was redissolved in EtOAc (500 mL)
- washwashed with satd
- extractionThe aqueous layer was extracted with EtOAc
- washthe combined extracts washed with brine (100 mL)
- dry with materialdried (Na2SO4)
- filtrationfiltered
- concentrationconcentrated in vacuo
- customThe crude product was purified by SiO2 chromatography
- washeluting with DCM/MeOH (10:1)
Sources & evidence
- ORD record
- ord-3df1ed7ce6264639b8e80b8cbe8bf23d
- Source dataset
- uspto-grants-2014_08
- Patent number
- US08815877B2
Reaction notes
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