Uses
Ethyl 5-amino-1-phenyl-4-pyrazolecarboxylate may be used as internal standard for the GC-MS determination of etomidate [ethyl-1-(1-phenylethyl)-1
H-imidazole-5-carboxylate] in mouse brain tissue.
Synthesis
General procedure for the synthesis of ethyl 5-amino-1-phenylpyrazole-4-carboxylate from phenylhydrazine and ethyl ethoxymethylcyanoacetate: ethyl 2-cyano-3-ethoxyacrylate (1.5 g, 8.9 mmol, 1.0 equiv.) was dissolved in ethanol (10 mL), followed by the addition of N,N-diisopropylethylamine (0.74 mL, 9.8 mmol, 1.1 equiv.) and phenylhydrazine (0.96 mL, 9.8 mmol, 1.1 equiv.). The reaction mixture was heated to 85 °C and stirred for 12 hours. Upon completion of the reaction, the mixture was concentrated to dryness and the residue was dissolved in a minimal amount of dichloromethane and purified by silica gel column chromatography (eluent: 20-30% ethyl acetate in hexane solution) to afford ethyl 5-amino-1-phenyl-1H-pyrazole-4-carboxylate (2.0 g, 96% yield) as an orange solid.MS (EI) m/z: 232 [M + H]+.
References
[1] Patent: WO2016/49500, 2016, A1. Location in patent: Paragraph 00217
[2] Cell Chemical Biology, 2018,
[3] Organic Letters, 2013, vol. 15, # 19, p. 5044 - 5047
[4] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 20, p. 4428 - 4433
[5] Tetrahedron, 2017, vol. 73, # 40, p. 5959 - 5973
