The synthesis and characterization of the 'research chemical' N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(cyclohexylmethyl)-3-(4-fluorophenyl)-1H-pyrazole-5-carboxamide (3,5-AB-CHMFUPPYCA) and differentiation from its 5,3-regioisomer.

Abstract

This study presents the identification of N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(cyclohexylmethyl)-3-(4-fluorophenyl)-1H-pyrazole-5-carboxamide that was termed 3,5-AB-CHMFUPPYCA. This compound was obtained from a UK-based Internet vendor, who erroneously advertised this 'research chemical' as AZ-037 and which would have been associated with (S)-N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(5-fluoropentyl)-5-(4-fluorophenyl)-1H-pyrazole-3-carboxamide. The presence of the pyrazole core indicates a bioisosteric replacement of an indazole ring that is frequently associated with synthetic cannabinoids of the PINACA, FUBINACA, and CHMINACA series. The pyrazole ring system present in 3,5-AB-CHMFUPPYCA gives rise to the regioisomer N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(cyclohexylmethyl)-5-(4-fluorophenyl)-1H-pyrazole-3-carboxamide (named 5,3-AB-CHMFUPPYCA) and both isomers were synthesized using two specific routes which supported the correct identification of the 'research chemical' as 3,5-AB-CHMFUPPYCA. Both isomers could be conveniently differentiated. Interestingly, a route specific chlorine-containing by-product also was observed during the synthesis of 3,5-AB-CHMFUPPYCA and identified as N-(1-amino-3-methyl-1-oxobutan-2-yl)-4-chloro-1-(cyclohexylmethyl)-3-(4-fluorophenyl)-1H-pyrazole-5-carboxamide. An extensive analytical characterization included chromatographic, spectroscopic, mass spectrometric platforms as well as crystal structure analysis. The syntheses and analytical characterizations of both AB-CHMFUPPYCA isomers are reported for the first time and serves as a reminder that the possibility of mislabeling of 'research chemicals' cannot be excluded. The pharmacological activities of both AB-CHMFUPPYCA isomers remain to be explored. Copyright © 2015 John Wiley & Sons, Ltd.