3-Methyl-1-[2-(trifluoromethyl)phenyl]-1H-pyrazol-5-amine

Synthesis

GENERAL METHOD: 3-Aminobut-2-enenenitrile (10 mmol) was added to a suspension of (2-(trifluoromethyl)phenyl)hydrazine (10 mmol) in 12 M HCl-H2O (12 mL, 1:3 v/v). The reaction mixture was heated to reflux for 12 h, subsequently cooled to room temperature and neutralized with 2.5 M NaOH solution. The reaction mixture was extracted with dichloromethane (3 x 30 mL). The organic phases were combined, washed with saturated saline (20 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was ground with hexane to give a solid product, which was separated by filtration. If necessary, the product was purified by column chromatography.

References

[1] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 11, p. 3429 - 3445
[2] Patent: WO2010/20363, 2010, A1. Location in patent: Page/Page column 136-137
[3] Journal of Combinatorial Chemistry, 2010, vol. 12, # 4, p. 510 - 517