5-Amino-1-(3-chlorophenyl)-1H-pyrazole-&

Synthesis

Sodium hydride (60% mineral oil dispersion, 0.48 g, 12 mmol, 1.2 eq.) was slowly added to anhydrous ethanol (20 ml) at 0 °C. To the resulting ethanol solution of sodium ethanol was sequentially added 3-chlorophenylhydrazine hydrochloride (1.79 g, 10 mmol, 1.0 eq.) and ethoxymethylene malononitrile (1.22 g, 10 mmol, 1.0 eq.). The reaction mixture was heated to reflux with continuous stirring for 1 hour. After completion of the reaction, the mixture was cooled to room temperature and precipitation was observed to be generated. Anhydrous ethanol (20 ml) was added to the reaction mixture for dilution, the precipitate was collected by filtration, washed with ether (2 x 100 ml) and dried under vacuum to afford the target compound 5-amino-1-(3-chlorophenyl)-1H-pyrazole-4-carbonitrile as a yellow solid (1.56 g, 7.13 mmol, 72% yield).LCMS analysis: [M + H]+ = 219, retention time Rt = 1.17min, purity 100%.

References

[1] Patent: EP1746099, 2007, A1. Location in patent: Page/Page column 14
[2] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 24, p. 7451 - 7454
[3] Journal of Heterocyclic Chemistry, 2012, vol. 49, # 6, p. 1425 - 1428