新型大麻模拟设计药物的详细结构阐明过程,N-(1-氨基-3,3-二甲基-1-氧代丁烷-2-基)-1-(5-氟戊基)-3-(4-氟苯基)-吡唑-5-甲酰胺,具有高度取代的吡唑骨架,描述了使用核磁共振(NMR)光谱和质谱(MS)技术。在对NMR光谱进行首次分析并与48种可能的吡唑和咪唑结构进行比较后,六个位置异构体吡唑和六个咪唑的子集仍然可以想象。确定了杂环骨架的四个取代基:与吡唑环碳原子结合的质子;5-氟戊基;4-氟苯基取代基;和氨基甲酰基,其被带有叔丁基的甲基残基N-取代。-丁基和氨基甲酰基取代基。5-氟戊基残基位于氮环原子上。额外的NMR实验,如(1)H,(13)进行CHMBC,但是由于基于远程耦合的信号数量很少,预测和观察到的(13)C化学位移的比较变得必要。开放存取互联网移位预测程序NMRDB,NMRSHIFTDB2和CSEARCH用于预测(13)C移位值,从而可以进行有效且明确的结构确定。对于鉴定的N-(1-氨基-3,3-二甲基-1-氧代丁烷-2-基)-1-(5-氟戊基)-3-(4-氟苯基)-吡唑-5-甲酰胺,预测的(13)C位移与观察到的吡唑环碳原子的化学位移和长程偶联之间的最佳一致性,标准误差约为2ppm,每个预测都被发现了。对于测量和预测的化学位移的比较,具有简单取代基的模型化合物被证明是有用的。所鉴定的化合物是由因特网供应商提供的AZ-037的同源物。版权所有©2015JohnWiley&Sons,Ltd.
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.