Acetic Acid → 4-(2,6-Difluoro-4-methoxyphenyl)-1,3-dimethyl-1H-pyrazole-5-amine
Reaction equation
[C:1]([CH:4]([C:7]1[C:12]([F:13])=[CH:11]C(OC)=C[C:8]=1[F:16])[C:5]#[N:6])(=O)[CH3:2].[C:17]([OH:20])(=O)[CH3:18].[CH3:21][NH:22][NH2:23].O.[CH2:25](O)C>CO>[F:16][C:8]1[CH:18]=[C:17]([O:20][CH3:25])[CH:11]=[C:12]([F:13])[C:7]=1[C:4]1[C:1]([CH3:2])=[N:23][N:22]([CH3:21])[C:5]=1[NH2:6]Participants
Conditions
- Temperature
- 45 °C
Procedure
α-Acetyl-2,6-difluoro-4-methoxybenzeneacetonitrile (i.e. the product of Step B) (8.03 g, 35.7 mmol) and acetic acid (5 mL) were stirred in ethanol (35 mL), and methylhydrazine (1.91 mL, 35.7 mmol) was added. The reaction mixture was heated at reflux for 16 h, cooled, and then poured into water (100 mL). The resulting mixture was extracted with ethyl acetate (100 mL). The organic phase was washed with 1 N aqueous NaOH (50 mL) and then brine (50 mL), dried over MgSO4, and concentrated to leave a solid. The solid was dissolved in methanol, and the resulting solution was warmed to 45° C. Water (25 mL) was added dropwise, and the mixture was allowed to cool. The precipitate was collected on a glass frit to give the title compound as a white solid (3.88 g).
Workup
- temperatureThe reaction mixture was heated
- temperatureat reflux for 16 h
- temperaturecooled
- extractionThe resulting mixture was extracted with ethyl acetate (100 mL)
- washThe organic phase was washed with 1 N aqueous NaOH (50 mL)
- dry with materialbrine (50 mL), dried over MgSO4
- concentrationconcentrated
- customto leave a solid
- temperatureto cool
- customThe precipitate was collected on a glass frit
Sources & evidence
- ORD record
- ord-4011e1bac5624c96b103f0d067df29b1
- Source dataset
- uspto-grants-2015_06
- Patent number
- US09062005B2
Reaction notes
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