title: Structure elucidation of the designer drug N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(5-fluoropentyl)-3-(4-fluorophenyl)-pyrazole-5-carboxamide and the relevance of predicted (13) C NMR shifts - a case study.
abstract: The detailed structure elucidation process of the new cannabimimetic designer drug, N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(5-fluoropentyl)-3-(4-fluorophenyl)-pyrazole-5-carboxamide, with a highly substituted pyrazole skeleton, using nuclear magnetic resonance (NMR) spectroscopic and mass spectrometric (MS) techniques is described. After a first analysis of the NMR spectra and comparison with 48 possible pyrazole and imidazole structures, a subset of six positional isomeric pyrazoles and six imidazoles remained conceivable. Four substituents of the heterocyclic skeleton were identified: a proton bound to a pyrazole ring carbon atom; a 5-fluoropentyl group; a 4-fluorophenyl substituent; and a carbamoyl group, which is N-substituted with a methyl residue carrying a tert.-butyl and a carbamoyl substituent. The 5-fluoropentyl residue is situated at the nitrogen ring atom. Additional NMR experiments like the (1) H,(13) C HMBC were performed, but due to the small number of signals based on long-range couplings, the comparison of predicted and observed (13) C chemical shifts became necessary. The open access Internet shift prediction programs NMRDB, NMRSHIFTDB2, and CSEARCH were employed for the prediction of (13) C shift values which allowed an efficient and unambiguous structure determination. For the identified N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(5-fluoropentyl)-3-(4-fluorophenyl)-pyrazole-5-carboxamide, the best agreement between predicted (13) C shifts and the observed chemical shifts and long-range couplings for the pyrazole ring carbon atoms, with a standard error of about 2 ppm, was found with each of the predictions. For the comparison of measured and predicted chemical shifts model compounds with simple substituents proved helpful. The identified compound is a homologue of AZ-037 which is offered by Internet suppliers. Copyright © 2015 John Wiley & Sons, Ltd.
authors.affiliation: Pharmaceutical Institute, Department of Pharmaceutical Chemistry, Christian-Albrechts-University of Kiel, Gutenbergstraße 76, Kiel, D-24118, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Girreser
authors.affiliation: Digilab Software GmbH, Posener Str. 18, Altenholz, D-24161, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Rösner
authors.affiliation: Republican Drug Dispensary of Health Care Ministry of Chuvash Republic, Pirogova Str. 6, Cheboksary, 428015, Chuvash Republic, Russia.
authors.forename: Andrej
authors.initials: A
authors.lastname: Vasilev
mesh_terms: D002186:Cannabinoids / Q000737:chemistry; D015198:Designer Drugs / Q000737:chemistry*; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D011720:Pyrazoles / Q000737:chemistry*
chemical_list: D002186:Cannabinoids; D015198:Designer Drugs; C000615635:N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(5-fluoropentyl)-3-(4-fluorophenyl)-pyrazole-5-carboxamide; D011720:Pyrazoles; C031280:pyrazole
keywords: 13C NMR; NMR spectroscopy; cannabimimetics; designer drugs; structure elucidation