{"paper_id":"fbc74738-9b00-4d35-9a14-8f45f4774582","body_text":"Fluorinated and fluoroalkylated pyrazoles\nhave attracted remarkable\nattention as privileged scaffolds in the design of pharmaceutical\nagents, crop protection chemicals, and advanced functional materials.  In this context, the 1-aryl-3-trifluoromethylpyrazole\ncore represents a particularly appealing structural motif for the\ndiscovery of new bioactive compounds ( Figure  \n ).  Introduction\nof a (hetero)­aryl substituent at C(5) has provided access to a broad\nspectrum of medicinally relevant molecules, including anti-inflammatory\nagents (e.g., celecoxib),  anticancer\ncandidates (SC-560),  antibacterial  and antifungal compounds,  and veterinary medicines (mavacoxib).  Derivatives bearing a furan2-yl unit (e.g., MPA14) exhibit\npronounced COX-1 inhibitory activity,  whereas analogues incorporating pyridine or thiophene rings have\nbeen applied in the treatment of asthma.  In addition, more complex architectures featuring an additional\nazole ring, such as 1,3,4-oxadiazole or pyrazole, located at C(5)\nhave been reported as promising coactivator-associated arginine methyltransferase\n1 (CARM1) antagonists,  and ATP-binding\ncassette transporting modulators,  respectively.\nSelected\nbioactive 1-aryl-3-CF 3 -pyrazoles.\nOn the other hand, installation of an amide functionality\nat C(5)\nof the 1-aryl-3-CF 3 -pyrazole framework has furnished a\ndiverse series of compounds with considerable potential in both agrochemical\nand medicinal chemistry.  Accordingly,\nmaterials featuring herbicidal,  parasiticidal,  insecticidal,  and\nnematicidal  as well as antiproliferative  and CARM1 inhibitory  properties have been described. Among these, particular attention\nshould be drawn to two marketed drugs: razaxaban,  an orally active inhibitor of coagulation factor Xa, and\nberotralstat,  a human plasma kallikrein\ninhibitor employed for the prophylactic treatment of hereditary angioedema\n(HAE).\nPrompted by the well-documented biological activity of\nboth aforementioned\nsubclasses of 1-aryl-3-trifluoromethylpyrazoles, and taking into account\nthe established significance of the 1,2,3-triazole motif in medicinal\nchemistry, frequently employed as bioisosteric replacement for amide\n(peptide) and related groups,  we envisaged\nthat the structurally related pyrazole–triazole hybrids of\ntype  1  might represent a valuable platform for the discovery\nof new bioactive molecules ( Scheme  \n ).\nA variety of non-fluorinated pyrazole-based\ncompounds bearing either\na 1,2,3- or 1,2,4-triazole ring have been extensively investigated\nin recent years.  The reported promising\nactivities encompass anticonvulsant,  antimicrobial,  antifungal,  anticancer, \n , \n  and tyrosinase inhibitory properties.  An elegant approach to cyclooxygenase inhibitors obtained via  in situ  click chemistry was demonstrated by Wuest,  in which the active site of the COX-2 isozyme\nserved as a reaction vessel, enabling the identification of two highly\npotent and selective products. Because of their high nitrogen content,\nseveral pyrazole–triazole hybrids functionalized with amino,\nazo and/or nitro groups have also been described as thermally stable\nenergetic materials of potential relevance to military, mining, and\naerospace applications.\nIn contrast,\nthe corresponding fluoromethylated structural motifs\nremain only sparsely explored.  In 2015,\nAtmakur et al. reported the synthesis of a library of CF 3 -functionalized pyrazoles linked to a 1,2,3-triazole ring through\nan acetamide-derived spacer ( Scheme  \n ).  The designed products\nwere obtained via a five-step sequence using 4,4,4-trifluoro-1-phenylbutane-1,3-dione\nas the key fluorinated substrate. Preliminary biological evaluation\nrevealed several promising lead compounds exhibiting an  in\nvitro  antimycobacterial activity. Shortly thereafter, the\nsame group disclosed a multistep synthesis of cytotoxic tricyclic\ndiazepine derivatives comprising directly bonded pyrazole and 1,2,3-triazole\nunits, starting with 4,4,4-trifluoro-3-oxobutanoate ( Scheme  \n ).  This ester was also employed by the Rajashakar group in the synthesis\nof fully substituted 5-(1,2,3-triazol-1-yl)-3-CF 3 -pyrazole-4-carbaldehyde\nderivatives.\nHowever, a general\nprotocol for the synthesis of trifluoromethylated\npyrazole–triazole hybrids of type  1 , closely resembling\nthe well-established 5-(hetero)­aryl- and 5-aminocarbonyl-functionalized\npyrazoles of practical significance, has not been described. Moreover,\nCF 3 -functionalized hydrazonoyl bromides  2  have\nemerged as a convenient alternative to the classical 1,3-dicarbonyl\nsubstrates typically employed in pyrazole synthesis.  Thus, in continuation of our study aimed at development\nof useful synthetic methodologies for fluorinated azoles,  here we report a rapid route to pyrazoles  1  via a three-step sequence comprising the formation of the\n1-aryl-3-CF 3 -pyrazole unit, its selective azidation, and\na copper-catalyzed azide–alkyne cycloaddition.\n\nWe commenced our study with\n1-aryl-3-trifluoromethylpyrazoles  3 , prepared according\nto the protocol recently developed in\nour laboratory.  The method relies on\na one-pot (3 + 3)-cycloaddition of mercaptoacetaldehyde with the nitrile\nimine generated  in situ  via base-mediated dehydrohalogenation\nof the corresponding bromides  2 , followed by a spontaneous\nEschenmoser-type ring contraction of the first formed 1,3,4-thiadiazine\nintermediate ( Scheme  \n ). Thus, starting from 1,4-dithiane-2,5-diol ( 4 ) (the\ndimer of mercaptoacetaldehyde) and nitrile imine precursors  2a – 2g , we obtained a series of eight model\npyrazoles  3a – 3g  bearing selected  para  substituents, i.e., X = Me (96%),  \n i \n Pr (85%), OMe (92%), OBn (97%), Cl (86%), CF 3  (70%),\nand CN (71%). All products were isolated in high yield.\nIn the synthesis of the key azides  5 , we benefited\nfrom the pronounced acidity of the C(5)– H  in\npyrazoles  3 .  Selective deprotonation\nwith a slight excess of  n -BuLi at −78 °C\nfurnished the corresponding lithium 5-pyrazolides, which upon treatment\nwith  p -toluenesulfonyl azide as an N 3 -transferring\nreagent underwent smooth functionalization to afford the desired series\nof 5-azidopyrazoles  5a – 5g . No significant\ninfluence of electronic effects on the reaction efficiency was observed;\npyrazoles with aryl residues bearing strongly electron-donating ( 5c ; X = OMe) and strongly electron-withdrawing ( 5f ; X = CF 3 ) substituents delivered the expected azides\nin 94% and 80% yield, respectively. The chloro- and cyano-substituted\nsubstrates also provided the desired azides  5e  (60%)\nand  5g  (37%) in somewhat lower yields, presumably due\nto side reactions with  n -BuLi (i.e., halogen–lithium\nexchange and nucleophilic addition, respectively). In the latter case,\nthe formation of an unidentified byproduct was noted; despite repeated\nattempts, it could not be removed by standard chromatography or recrystallization\ndue to limited stability of  5g , and the material (ca.\n90% purity) was therefore used in the next step without further purification.\nThe reaction proved to be readily scalable, delivering  5c  (X = OMe) in a comparable 90% yield when performed on a gram scale\n(1.9 g, 6.6 mmol).\nFor the initial click experiments, we employed\nazide  5a  and phenylacetylene ( Scheme  \n ). A brief screening of literature-reported\nconditions, \n , \n  during which the solvent (DCM,\nMeCN, aqueous MeOH) and the copper\nsource (CuSO 4 , (AcO) 2 Cu, CuI/DIPEA) were evaluated,\nallowed us to identify optimal reaction parameters. Thus, running\nthe reaction with a slight excess of the alkyne and a CuSO 4 /ascorbate catalytic system, in a MeOH/H 2 O (10:1 mixture)\nat 55 °C, ensured complete consumption of the starting azide.\nThe analytically pure sample of the expected (3 + 2)-cycloadduct  1aa  was isolated in high 85% yield after simple filtration\nof the crude product through a short plug of silica gel, followed\nby recrystallization from hexanes. With these conditions in hand,\na first set of phenylacetylene-derived products  1aa – 1ag  were obtained in good yields (67–86%), regardless\nof the electronic nature of the substituents or functional groups\npresent in the starting azides.\nNext, we examined the scope\nwith respect to the alkyne reaction\npartners using 4-methoxyphenyl-substituted azide  5c  ( Scheme  \n ). A series of  para -substituted phenylacetylenes was checked, affording\nthe corresponding 1,2,3-triazoles bearing primary amino ( 1ba ), alkyl ( 1bc - 1bd , Me, and n-Pent), halogen\n( 1be , Cl), or cyano ( 1bf ) groups. Introduction\nof an electron-rich OMe donor at the  para ,  meta , or  ortho  position of the aromatic\nring exerted only a marginal influence on the reaction efficiency,\nwith the  ortho -substituted product  1bg  isolated in 91% yield and an excellent 79% overall yield (for three\nsteps). The structure of  para -functionalized isomer  1bb  was unambiguously confirmed by X-ray diffraction (CCDC  2425718 ).\nBoth increased substitution, as in  1bi  (2,4,6-trimethyl),\nand extension of the π system, as in naphthyl derivative  1bj , were well-tolerated. Electron-deficient fluorinated phenylacetylenes\nbearing one or two substituents, i.e., fluorine atoms or fluoroalkyl\ngroups (CF 3 , OCF 3 ), did not hamper the reaction,\nconsistently providing products  1bk – 1bo  in yields exceeding 80%. In the case of 1,4-diethynylbenzene, the\napplied conditions furnished a mixture of two products,  1bt  (53%) and  1bu  (15%). Fine-tuning of the reactant stoichiometry\nprovided excellent control over the reaction outcome, enabling the\nselective formation of the corresponding monocycloadducts (using 1.6\nequiv of alkyne) and biscycloadducts (using 2.5 equiv of azide), which\nwere isolated in 83% and 56%, respectively. Incorporation of pyridyl\nand thienyl units, as exemplary six- and five-membered heteroaryl\nsubstituents, furnished  1br  and  1bs  in 73%\nand 87% yield, respectively. Moreover, reaction of an acetylene bearing\nferrocene moiety, selected as a representative organometallic counterpart,\nalso proceeded smoothly to afford the expected cycloadduct ( 1bq , 66%).\nAliphatic alkynes were checked as well; the\n(3 + 2)-cycloaddition\nreactions of 1-octyne and  tert -butylacetylene delivered\nthe expected products  1ca  and  1cb , although\nin the latter case, the sterically crowded product was obtained in\ndiminished yield. Trimethylsilylacetylene was used as a surrogate\nfor acetylene; due to spontaneous cleavage of the C–Si bond\nduring the aqueous workup, the desired hybrid  1cc , lacking\na substituent at C(4) of the 1,2,3-triazole ring, was isolated. Introduction\nof functional groups such as hydroxymethyl, diethoxymethyl, and methoxycarbonyl\nwas readily accomplished by employing the respective acetylenes, although\nproduct  1ce  bearing a masked carbonyl group was accessed\nin a markedly lower yield (35%) due to partial hydrolysis of the acetal\nmoiety. In addition, two multifunctional building blocks, BMK-alkyne\nand hydroxyl-diazirine-alkyne, often used as probes for selective\nmodification of biological targets, were checked in reactions with\nmodel azide  5c  under the optimal reaction conditions\n(CuSO 4 /sodium ascorbate, MeOH/H 2 O, 55 °C,\n5 h). Accordingly, new derivatives  1cg  (41%) and  1ch  (81%) suitable for potential  19 F labeling of\nbiomolecules were obtained.\nTo\nfurther assess the synthetic potential of 5-azido-CF 3 -pyrazole  5c  in the modification of more complex systems,\na series of well-known pharmaceuticals bearing terminal alkyne functionality\nwas involved in the study ( Scheme  \n ). Two monoamine oxidase inhibitors, pargyline and\nrasagiline,  featuring secondary and\ntertiary amine groups, respectively, provided the expected cycloadducts  1da  (68%) and  1dc  (77%). Notably, the optical\npurity of the latter substrate remained unchanged during the (3 +\n2)-cycloaddition step, leading to an enantiopure pyrazole–triazole\nhybrid. Moreover, erlotinib,  a tyrosine\nkinase inhibitor used as first-line therapy for advanced nonsmall-cell\nlung cancer, as well as gestrinone,  a\nsynthetic steroid hormone approved for the treatment of endometriosis,\nprovided the expected cycloadducts in excellent yields of 84% ( 1db ) and 87% ( 1dd ).\nThe presence of hydroxyl\nand cyano functionalities in the pyrazole–triazole\nhybrids  1bp  and  1bf , respectively, offers\nseveral opportunities for postcyclizative modifications of the heterocyclic\nframework ( Scheme  \n ). For example, straightforward acylation of the hydroxy group in  1bp  with Ac 2 O afforded ester  1bv  in\n91% yield, whereas oxidation with the Corey–Suggs reagent furnished\nthe corresponding aldehyde  1bw  almost quantitatively.\nThe methoxycarbonyl moiety in  1bx  was introduced efficiently\nby permanganate-mediated oxidation in wet MeCN, followed by Fischer\nesterification, giving the product in an overall 93% yield.\na Yields refer to analytically\npure samples obtained by chromatography, followed by recrystallization. \n b Using 1.6 equiv of 1,4-diethynylbenzene. \n c Using 2.5 equiv of azide  5c . \n d TMS-acetylene\nwas used as a reaction partner. \n e 1.5 equiv of azide  5c , reaction time of 40 h. \n f 1.5 equiv of azide  5c , reaction time of 16 h.\nYields refer to analytically\npure samples obtained by chromatography, followed by recrystallization.\nUsing 1.6 equiv of 1,4-diethynylbenzene.\nUsing 2.5 equiv of azide  5c .\nTMS-acetylene\nwas used as a reaction partner.\n1.5 equiv of azide  5c , reaction time of 40 h.\n1.5 equiv of azide  5c , reaction time of 16 h.\nFor the transformation\nof the cyano group into the primary amide,\nwe employed classical conditions of the Radziszewski-type reaction,  relying on H 2 O 2 -induced\nhydrolysis under basic conditions. Thus, treatment of  1bf  with an excess of hydrogen peroxide in the presence of Na 2 CO 3  at room temperature furnished amide  1by  in an excellent yield of 94%.\nExhaustive reduction of the\ncyano group, proceeding  via  reductive deamination\nof the initially formed amine,  was observed\nupon catalytic hydrogenation at\nelevated pressure (70 psi) using palladium on charcoal as the catalyst.\nThe corresponding product bearing the  p -tolyl substituent\nwas obtained quantitatively, and its identity with the original sample  1bc , prepared independently through azide–alkyne (3\n+ 2)-cycloaddition reaction ( Scheme  \n ) was confirmed by NMR analysis. The desired amine\nwas accessible under milder hydrogenation conditions (H 2 , slight positive pressure from balloon) employing Raney-Ni as the\ncatalyst; the first formed product was subsequently acylated with\nisobutyryl chloride to furnish the corresponding amide  1bz  in a fair overall yield of 74%. These experiments clearly demonstrate\nthe remarkable stability of the designed 1-aryl-5-(1,2,3-triazol-1-yl)-3-CF 3 -pyrazole core under both harsh reductive and oxidative conditions\nand establish these pyrazole hybrids as robust building blocks for\nconstruction of more elaborate molecular architectures.\na Ac 2 O, DCM,\n40 °C,\n90 min. \n b PCC, DCM, rt, 3\nh. \n c KMnO 4 , MeCN,\n80 °C, 2 h, then MeOH, H 2 SO 4 , reflux 12\nh. \n d H 2 O 2 , Na 2 CO 3 , acetone rt, 2 h. \n e H 2  (70 psi), Pd/C, THF, rt, 5 h. \n f H 2 , Raney-Ni, NH 3 aq, rt, 2 h, then i-PrCOCl, Et 3 N, THF, rt, 1 h.\nAc 2 O, DCM,\n40 °C,\n90 min.\nPCC, DCM, rt, 3\nh.\nKMnO 4 , MeCN,\n80 °C, 2 h, then MeOH, H 2 SO 4 , reflux 12\nh.\nH 2 O 2 , Na 2 CO 3 , acetone rt, 2 h.\nH 2  (70 psi), Pd/C, THF, rt, 5 h.\nH 2 , Raney-Ni, NH 3 aq, rt, 2 h, then i-PrCOCl, Et 3 N, THF, rt, 1 h.\nFinally, to check whether the isomeric hybrids\nbearing the 1,2,3-triazole\nmoiety at C(4) of the pyrazole core could be accessed, a plausible\nC(4)-iodination/lithiation/azide-transfer sequence was investigated.\nAs depicted in  Scheme  \n , the representative substrate  3a  was converted in fully\nregioselective fashion into the corresponding iodide  7  using a slight excess of elemental iodine and ceric ammonium nitrate\n(CAN) as a mild oxidant.  To our delight,\nthe subsequent iodine–lithium exchange in  7  (X\n= I) proceeded smoothly, and after N 3  transfer the expected\nazide  8  (X = N 3 ) was obtained, albeit in a\nmoderate yield of 42%. Cu-catalyzed (3 + 2)-cycloaddition of  8  with phenylacetylene, furnishing the 4-(1,2,3-triazol-1-yl)­pyrazole\nderivative  9  (68%), thus demonstrated the feasibility\nof the designed approach.\na I 2  (1.3\nequiv), CAN\n(1.1 equiv), MeCN, reflux, 16 h. \n b \n \n n \n BuLi, THF, −78 °C, then\nTsN 3  rt, 4 h. \n c Ph−C≡CH, CuSO 4 , sodium ascorbate, MeOH/H 2 O (10:1), 55 °C, 5 h.\nI 2  (1.3\nequiv), CAN\n(1.1 equiv), MeCN, reflux, 16 h.\nn \n BuLi, THF, −78 °C, then\nTsN 3  rt, 4 h.\nPh−C≡CH, CuSO 4 , sodium ascorbate, MeOH/H 2 O (10:1), 55 °C, 5 h.\n\nIn summary, a method for the rapid assembly\nof trifluoromethylated\npyrazole–triazole hybrids inspired by the structural motifs\nof numerous biologically relevant 3-CF 3 -pyrazole derivatives\nof practical significance is presented. By employing a three-step\nsequence comprising a (3 + 3)-cycloaddition/Eschenmoser-type ring\ncontraction cascade affording 1-arylpyrazoles, followed by C(5)-selective\nazidation and Cu-catalyzed Huisgen cycloaddition, a broad set of variously\nfunctionalized hybrids was obtained in high overall yields. Sterically\ndemanding substrates, including the synthetic steroidal drug gestrinone,\nas well as more challenging alkynes bearing additional (photo)­labile\nfunctionalities or strongly electron-deficient and -rich substituents,\nwere generally well tolerated. Moreover, selected functional group\ninterconversions performed under harsh reductive or oxidative conditions\ndemonstrated the remarkable stability of the bis-heterocyclic core\nand highlighted its robustness. Thus, the developed protocol can be\nrecommended for the preparation of more advanced analogues. Biological\nevaluation of selected hybrids is currently underway in our laboratories\nand will be reported in a separate study.\n\nAll commercially available reagents and solvents\nwere used as received. Products were purified by filtration through\na short plug of silica gel (FCC) or standard column chromatography\n(CC) (SiO 2 , 230–400 mesh) by using freshly distilled\nsolvents and recrystallized from appropriate solvents. NMR spectra\nwere taken on a Bruker AVIII instrument ( 1 H at 600 MHz,  13 C at 151 MHz, and  19 F NMR at 565 MHz); chemical\nshifts are reported relative to the solvent residual peaks [for CDCl 3 :  1 H NMR: δ = 7.26,  13 C NMR: δ\n= 77.16; for DMSO- d \n 6 :  1 H NMR:\nδ = 2.50,  13 C NMR: δ = 39.52] or to CFCl 3  (δ = 0.00) used as an external standard. The IR spectra\nwere taken with an Agilent Cary 630 FTIR spectrometer, in neat. (ESI)-MS\nwas performed with a Varian 500-MS LC ion trap; high-resolution MS\n(ESI-TOF) measurements were performed with a Waters Synapt G2-Si mass\nspectrometer. Combustion analyses were obtained with a Vario EL III\n(Elementar Analysensysteme GmbH) instrument. Optical rotations were\ndetermined with a PerkinElmer 241 polarimeter at the temperatures\nindicated. Melting points were determined in capillaries with a MEL-TEMP\napparatus (Laboratory Devices) or with a polarizing optical microscope\n(POM) (Opta-Tech) and are uncorrected. Single crystals of  1bb  were measured on a XtaLAB Synergy, Dualflex, Pilatus 300 K diffractometer\nusing mirror-focused Cu Kα radiation. Crystallographic data\nhave been deposited at the Cambridge Crystallographic Data Center\nas supplementary publication number CCDC  2425718 . These data can be obtained free of charge from\nthe CCDC, 12 Union Road, Cambridge CB2 1EZ, U.K.; fax: + 44 (0) 1223\n336 033; email:  deposit@ccdc.cam.ac.uk  (or via  http://www.ccdc.cam.ac.uk/conts/retrieving.html ).\nA mixture of 5-azidopyrazole  5  (1.00 mmol), acetylene (1.20 mmol), copper­(II) sulfate pentahydrate\n(38 mg, 0.15 mmol), and sodium  l -ascorbate (59.5 mg, 0.30\nmmol) in MeOH/H 2 O (10:1, 14 mL) was stirred at 55 °C\n(oil bath) until the starting pyrazole was fully consumed (typically\nup to 5 h; TLC monitoring). The solvents were then evaporated, and\nthe crude reaction mixture was dissolved in DCM (20 mL), dried over\nNa 2 SO 4 , and filtered through a Celite pad, which\nwas washed with additional portions of DCM (2 × 8 mL). After\nthe solvent was removed  in vacuo , product  1  was purified by flash column chromatography (FCC) and recrystallized.\nFCC (SiO 2 , hexane/EtOAc 4:1); colorless\nsolid, 314 mg (85%); mp 120–122 °C (hexane).  1 H NMR (600 MHz, CDCl 3 ) δ: 7.80–7.79 (m, 2H),\n7.75 (s, 1H), 7.45–7.43 (m, 2H), 7.39–7.36 (m, 1H),\n7.20–7.17 (m, 4H), 7.00 (s, 1H), 2.35 (s, 3H).  13 C­{ 1 H} NMR (151 MHz, CDCl 3 ) δ 148.5, 143.0\n(q,  2 \n J \n C–F  = 39.6 Hz),\n140.2, 135.8, 134.5, 130.3, 129.4, 129.2, 129.1, 126.1, 124.3, 121.6,\n120.7 (q,  1 \n J \n C–F  = 269.6\nHz), 103.0 (q,  3 \n J \n C–F  = 2.2 Hz), 21.3.  19 F NMR (565 MHz, CDCl 3 )\nδ −62.76 (s, CF 3 ). IR (neat): ν 3153,\n2963, 1580, 1502, 1364, 1238, 1156, 1139, 1014 cm –1 . (+)-ESI-MS ( m / z ): 370.4 (100,\n[M + H] + ). Anal. Calcd for C 19 H 14 F 3 N 5  (369.4): C, 61.79; H, 3.82; N, 18.96.\nFound: C, 61.70; H, 3.98; N, 19.07.\nTo a solution of 1-aryl-3-(trifluoromethyl)­pyrazole  3  (1.00 mmol) in anhydrous THF (10 mL), at −78 °C, under\nargon, was added  n -BuLi (2.5 M in hexane, 0.52 mL,\n1.30 mmol). After 5 min, a solution of tosyl azide (405 mg, 2.05 mmol)\nin dry THF (5 mL) was added dropwise. The reaction mixture was allowed\nto warm to room temperature and stirred for 4 h. The reaction was\nquenched with 1 M NH 4 Cl­(aq) solution (15 mL) and extracted\nwith DCM (3 × 20 mL). The combined organic layers were washed\nwith water (3 × 10 mL), dried over Na 2 SO 4 , and filtered, and the solvents were removed  in vacuo . The crude product  5  was purified by standard column\nchromatography on silica gel (CC).\nCC (SiO 2 , hexane/DCM 4:1); red solid, 222 mg (83%); mp 45–47 °C.  1 H NMR (600 MHz, CDCl 3 ) δ: 7.48–7.45\n(m, 2H), 7.29–7.27 (m, 2H), 6.45 (s, 1H), 2.41 (s, 3H).  13 C­{ 1 H} NMR (151 MHz, CDCl 3 ) δ\n142.9 (q,  2 \n J \n C–F  = 38.7\nHz), 139.4, 139.0, 134.9, 129.8, 124.0, 120.9 (q,  1 \n J \n C–F  = 268.7 Hz), 94.1 (q,  3 \n J \n C–F  = 2.5 Hz), 21.3.  19 F NMR (565 MHz, CDCl 3 ) δ −63.02 (s, CF 3 ). IR (neat): ν 2922, 2136 (N 3 ), 1517, 1472,\n1282, 1233, 1162, 1107, 972, 816 cm –1 . (+)-ESI-MS\n( m / z ): 268.3 (100, [M + H] + ); Anal. Calcd for C 11 H 8 F 3 N 5  (267.2): C, 49.44; H, 3.02; N, 26.21. Found: C, 49.40; H,\n3.02; N, 26.19.","source_license":"CC-BY-4.0","license_restricted":false}