4-Methylphenylhydrazine monohydrochloride → 1-p-tolyl-3-(1-(trifluoromethyl)cyclopropyl)-1H-pyrazol-5-amine

HRID 631699Notes

Reaction equation

[C:1]1([N:7]2[C:11]([NH2:12])=[CH:10][C:9]([C:13]3([C:16]([F:19])([F:18])[F:17])[CH2:15][CH2:14]3)=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[Na+].Cl.[C:23]1(C)C=CC(NN)=CC=1>CCO.O>[C:4]1([CH3:23])[CH:3]=[CH:2][C:1]([N:7]2[C:11]([NH2:12])=[CH:10][C:9]([C:13]3([C:16]([F:18])([F:19])[F:17])[CH2:15][CH2:14]3)=[N:8]2)=[CH:6][CH:5]=1

Participants

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-cc13b2d582954507a4990acf170be557
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09320739B2

Reaction notes

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