4-Methylphenylhydrazine monohydrochloride → 1-p-tolyl-3-(1-(trifluoromethyl)cyclopropyl)-1H-pyrazol-5-amine
Reaction equation
O=[C:2]([C:6]1([C:9]([F:12])([F:11])[F:10])[CH2:8][CH2:7]1)[CH2:3][C:4]#[N:5].[OH-].[Na+].Cl.[C:16]1([CH3:24])[CH:21]=[CH:20][C:19]([NH:22][NH2:23])=[CH:18][CH:17]=1>CCO.O>[C:16]1([CH3:24])[CH:21]=[CH:20][C:19]([N:22]2[C:4]([NH2:5])=[CH:3][C:2]([C:6]3([C:9]([F:10])([F:11])[F:12])[CH2:8][CH2:7]3)=[N:23]2)=[CH:18][CH:17]=1Participants
6
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 80 °C
Procedure
To a solution of 3-oxo-3-(1-(trifluoromethyl)cyclopropyl)propanenitrile (500 mg, 2.8 mmol) (from Example 137A Step 2) in EtOH (10 mL) was added water (7.2 mL) and 1 M NaOH (2.8 mL) followed by p-tolylhydrazine hydrochloride (444 mg, 2.8 mmol) and the solution heated at 80° C. overnight. The solution was cooled to rt, diluted with water and extracted with 2 portions of EtOAc. The combined extracts were washed with brine, dried over magnesium sulfate, filtered, and concentrated. The crude solid was purified using silica gel chromatography using a gradient of 5-25% EtOAc/hexane to give 1-p-tolyl-3-(1-(trifluoromethyl)cyclopropyl)-1H-pyrazol-5-amine (452 mg, 57% yield). LC-MS (ESI) m/z 282 (M+H)+
Workup
- temperatureThe solution was cooled to rt
- extractionextracted with 2 portions of EtOAc
- washThe combined extracts were washed with brine
- dry with materialdried over magnesium sulfate
- filtrationfiltered
- concentrationconcentrated
- customThe crude solid was purified
Sources & evidence
- ORD record
- ord-44e5f9b1fc894dfd970d4fd6833aa5a0
- Source dataset
- uspto-grants-2015_03
- Patent number
- US08969587B2
Reaction notes
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