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Molecules 2016, 21(10), 1268; doi:10.3390/molecules21101268

Communication
Palladium-Catalyzed C–H Arylation of 1,2,3-Triazoles
Department of Biochemistry, UT Southwestern Medical Center, Dallas, TX 75390, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Georgiy B. Shul’pin
Received: 5 August 2016 / Accepted: 16 September 2016 / Published: 22 September 2016

Abstract

:
Palladium(II) acetate, in combination with triphenylphosphine, catalyzes direct arylation of 1,4-disubstituted 1,2,3-triazoles effectively. This C–H arylation reaction provides facile access to fully substituted triazoles with well-defined regiochemistry.
Keywords:
C–H arylation; palladium; triazole

1. Introduction

1,2,3-Triazole has attracted increasing attention in medicinal chemistry and material sciences because of the recent development of transition metal-catalyzed Huisgen 1,3-dipolar cycloaddition of azides and terminal alkynes [1,2,3,4,5,6,7]. In contrast to the thermal process that is not regioselective, the copper(I)- and ruthenium(II)-catalyzed methods afford 1,4- and 1,5-disubstituted 1,2,3-triazoles, respectively [8,9,10,11,12,13]. Methods such as in situ cross-coupling or transmetallation of the triazolyl cuprate intermediate have also been developed to allow for the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles with well-defined regiochemistry [14,15,16,17,18,19,20,21]. However, C–H functionalization of disubstituted triazoles is arguably the most versatile and convenient way to construct 1,4,5-trisubstituted 1,2,3-triazoles [22,23,24,25,26,27]. During a recent structure–activity relationship study of a triazole-class of small-molecule Wnt inhibitors, we found that the reported C–H arylation methods gave very low yields of the coupling products. We report herein the identification of new coupling conditions that supported the synthesis of fully substituted 1,2,3-triazoles.

2. Results

Our study commenced with the optimization of the reaction parameters for coupling triazole 1 with phenyl bromide, as the reported methods gave a yield of only <20% of the arylation product 2 (Table 1, entries 1 and 2) [22,23]. Based on our experience in heterocycle C–H arylation [28], we chose the concerted metalation-deprotonation (CMD)-type palladium-catalyzed method [29,30,31,32,33,34,35,36,37]. After a brief survey of reaction parameters based on Gevorgyan’s protocol [22], we focused on studying the effects of ligand and base (Table 1). We found that potassium carbonate was a more effective base (entries 3–5), and triphenylphosphine promoted the coupling reaction to give 2 with significantly increased yields (entries 5–13). Switching the solvent to toluene further improved the conversion (entry 14).
With suitable coupling conditions in hand, we tested the scope of this C–H arylation reaction (Table 2). The coupling of 3 with aryl bromide proceeded well except for a few cases. In general, 4-substituted aryl bromides reacted smoothly regardless of their electronic properties (entries 1–5). Only 4-fluorophenyl bromide reacted with 1 slowly (entry 6). However, this coupling reaction is sensitive to electronic perturbation at the 3-position of the aryl bromide. Although introduction of a slightly electron-rich methyl group did not affect the coupling efficiency (entry 7), the presence of an electron-withdrawing aldehyde group resulted in the formation of multiple by-products (entry 8). The reaction is also sensitive to steric perturbation at the 2-position of the aryl bromide. Coupling of 1 with 2-methoxyphenyl bromide gave a good yield of the desired product (entry 9), but the reaction of 1 and 2-bromotoluene proceeded with a modest conversion (entry 10). The coupling of 1 and 1-naphthyl bromide was also slightly slower (entry 11).
C–H arylation of various other triazoles also proceeded well. There is no reduction in coupling efficiency for 3-pyridyl, 2-pyridyl, and phenyl-substituted triazoles 3 (entries 12–14). However, the introduction of a 4-methoxyl or a 2-trifluoromethyl group at the C4-position led to decreased yields of 4 (entries 15 and 16). The reaction of 2-trifluoromethylphenyl substituted triazole 3 with phenyl bromide also gave a 29% yield of the corresponding α-arylation product [38,39,40], in addition to the desired C–H arylation product. No reaction occurred with α-substituted triazoles 3 due to the congested environment around the triazole C–H. Performing the reaction with microwave-heating at a slightly higher temperature gave a small amount of products, but a prolonged reaction time led to significant decomposition (entries 17 and 18).

3. Materials and Methods

3.1. General Methods

All reactions were performed in glassware under a positive pressure of argon. Flash column chromatography was performed on a Teledyne ISCO CombiFlash Rf 200 system (Isco, Inc., Lincoln, NE, USA) using silica gel 60 (230–400 mesh). Thin layer chromatography (TLC) analyses were performed on EMD 250 μm Silica Gel 60 F254 plates (Merck KGaA, Darmstadt, Germany) and visualized by quenching of UV fluorescence (λmax = 254 nm) or by staining with ceric ammonium molybdate. 1H-NMR spectra were recorded on a Varian Inova-400 instrument (Varian, Inc., Palo Alto, CA, USA). Chemical shifts are reported in ppm (δ) relative to the residual solvent signals of the solvent (δ 7.26 for CHCl3), coupling constants (J) are reported in Hz and the multiplicities are presented as follows: s = singlet, brs = broad singlet, d = doublet, t = triplet, q = quartet, and m = multiplet. Mass spectra were acquired on Agilent 6120 Single Quadrupole Liquid Chromatography tandem Mass Spectrometer (LC/MS) (Agilent Technologies, Santa Clara, CA, USA). High-resolution mass spectrum was acquired by the Mass Spectrometry Facility at the University of Austin.

3.2. General Precedure for C–H Arylation and Compound Characterization

Palladium(II) acetate (10 mol %), triphenylphosphine (20 mol %), potassium carbonate (2.0 equiv.) and aryl bromide (3.0 equiv.) were added to a solution of triazole 3 (1.0 equiv.) in toluene. After stirring for 24 h at 120 °C, the mixture was quenched with saturated ammonium chloride and extracted with ethyl acetate. The combined organic layers were washed with brine and dried over sodium sulfate. The solvent was removed under a vacuum, and the residue was purified by flash column chromatography on silica gel to provide 4.
tert-Butyl 2-(5-phenyl-4-(pyridin-4-yl)-1H-1,2,3-triazol-1-yl)acetate (2). White solid; IR (neat, cm–1) 3402, 2219, 1615, 1506, 1456, 1368, 1236, 1157, 1048; 1H-NMR (400 MHz, CDCl3) δ 8.52 (brs, 2H), 7.59–7.55 (m, 5H), 7.37–7.34 (m, 2H), 4.90 (s, 2H), 1.39 (s, 9H); 13C-NMR (100 MHz, CDCl3) δ 165.3, 150.0, 141.6, 138.3, 136.2, 130.4, 129.6, 129.5, 126.6, 120.5, 83.6, 49.9, 27.8; High resolution mass spectrometry (HRMS)-electrospray ionization (ESI) (m/z): calcd. for C19H21N4O2 [M + H]+ 337.1659, found 337.1666.
tert-Butyl 2-(5-(4-methoxyphenyl)-4-(pyridin-4-yl)-1H-1,2,3-triazol-1-yl)acetate. White solid; 1H-NMR (400 MHz, CDCl3) δ 8.49 (brs, 2H), 7.50 (d, J = 5.2 Hz, 2H), 7.25 (d, J = 8.4 Hz, 2H), 7.03 (d, J = 8.4 Hz, 2H), 4.87 (s, 2H), 3.88 (s, 3H), 1.40 (s, 9H); 13C-NMR (100 MHz, CDCl3) δ 165.5, 161.3, 149.6, 141.6, 139.2, 136.4, 131.2, 120.7, 118.2, 115.2, 83.8, 55.6, 49.9, 28.0; MS-ESI (m/z): calcd. for C20H23N4O3 [M + H]+ 367.2, found 367.2.
tert-Butyl 2-(5-(4-ethoxycarbonylphenyl)-4-(pyridin-4-yl)-1H-1,2,3-triazol-1-yl)acetate. White solid; 1H-NMR (400 MHz, CDCl3) δ 8.51 (brs, 2H), 8.20 (d, J = 8.0 Hz, 2H), 7.49 (d, J = 4.8 Hz, 2H), 7.45 (d, J = 8.4 Hz, 2H), 4.90 (s, 2H), 4.44 (q, J = 7.2 Hz, 2H), 1.44–1.39 (m, 12H); 13C-NMR (100 MHz, CDCl3) δ 165.6, 165.2, 149.2, 141.8, 139.2, 135.7, 132.7, 131.1, 130.8, 130.0, 121.0, 84.2, 61.8, 50.1, 28.0, 14.4; MS-ESI (m/z): calcd. for C22H25N4O4 [M + H]+ 409.2, found 409.2.
tert-Butyl 2-(4-(pyridin-4-yl)-5-(4-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-1-yl)acetate. White solid; 1H-NMR (400 MHz, CDCl3) δ 8.52 (brs, 2H), 7.79 (d, J = 8.0 Hz, 2H), 7.51 (d, J = 8.0 Hz, 2H), 7.41(d, J = 4.8 Hz, 2H), 4.90 (s, 2H), 1.38 (s, 9H); 13C-NMR (100 MHz, CDCl3) δ 165.2, 150.2, 142.2, 138.1, 134.8, 132.9, 132.5, 130.7, 130.5, 126.7(q, J = 3.7 Hz), 125.0, 122.2, 120.9, 84.2, 50.2, 27.9; MS-ESI (m/z): calcd. for C20H20F3N4O2 [M + H]+ 405.2, found 405.2.
tert-Butyl 2-(5-(4-cyanophenyl)-4-(pyridin-4-yl)-1H-1,2,3-triazol-1-yl)acetate. White solid; 1H-NMR (400 MHz, CDCl3) δ 8.55 (brs, 2H), 7.84 (d, J = 8.0 Hz, 2H), 7.53 (d, J = 8.4 Hz, 2H), 7.45 (d, J = 4.4 Hz, 2H), 4.91 (s, 2H), 1.40 (s, 9H); 13C-NMR (100 MHz, CDCl3) δ 165.1, 149.4, 142.2, 138.8, 134.7, 133.4, 131.6, 130.8, 121.1, 117.7, 114.9, 84.5, 50.2, 28.0; MS-ESI (m/z): calcd for C20H20N5O2 [M + H]+ 362.2, found 362.2.
tert-Butyl 2-(5-(4-fluorophenyl)-4-(pyridin-4-yl)-1H-1,2,3-triazol-1-yl)acetate. White solid; 1H-NMR (400 MHz, CDCl3) δ 8.51 (brs, 2H), 7.49 (d, J = 4.8 Hz, 2H), 7.37–7.34 (m, 2H), 7.26–7.22 (m, 2H), 4.88 (s, 2H), 1.40 (s, 9H); 13C-NMR (100 MHz, CDCl3) δ 165.3, 148.9, 141.7, 135.8, 132.0 (d, J = 8.5 Hz), 130.9, 129.9 (d, J = 13.4 Hz), 122.5 (d, J = 3.5 Hz), 117.3 (d, J = 21.9 Hz), 110.1, 84.1, 50.0, 28.0; MS-ESI (m/z): calcd. for C19H20FN4O2 [M + H]+ 355.2, found 355.2.
tert-Butyl 2-(5-(3-methylphenyl)-4-(pyridin-4-yl)-1H-1,2,3-triazol-1-yl)acetate. White solid; 1H-NMR (400 MHz, CDCl3) δ 8.51 (brs, 2H), 7.49 (brs, 2H), 7.42–7.34 (m, 2H), 7.14 (s, 1H), 7.12 (d, J = 9.2 Hz, 1H), 4.86 (s, 2H), 2.38 (s, 3H), 1.39 (s, 9H); 13C-NMR (100 MHz, CDCl3) δ 165.5, 149.9, 141.6, 139.7, 138.8, 136.5, 131.4, 130.2, 129.6, 126.8, 126.6, 120.8, 83.8, 50.0, 27.9, 21.5; MS-ESI (m/z): calcd. for C20H23N4O2 [M + H]+ 351.2, found 351.2.
tert-Butyl 2-(5-(3-formylphenyl)-4-(pyridin-4-yl)-1H-1,2,3-triazol-1-yl)acetate. White solid; 1H-NMR (400 MHz, CDCl3) δ 10.06 (s, 1H), 8.10 (d, J = 8.0 Hz, 1H), 7.92 (s, 1H), 7.75 (t, J = 7.6 Hz, 1H), 7.68–7.62 (m, 2H), 7.54–7.52 (m, 2H), 7.47–7.45 (m, 1H), 4.91 (s, 2H), 1.39 (s, 9H); 13C-NMR (100 MHz, CDCl3) δ 190.9, 165.3, 150.3, 135.8, 132.3, 132.2, 132.1, 132.1, 130.7, 130.6, 128.7, 128.6, 120.8, 84.3, 50.2, 28.0; MS-ESI (m/z): calcd. for C20H21N4O3 [M + H]+ 365.2, found 365.2.
tert-Butyl 2-(5-(2-methoxyphenyl)-4-(pyridin-4-yl)-1H-1,2,3-triazol-1-yl)acetate. White solid; 1H-NMR (400 MHz, CDCl3) δ 8.50 (brs, 2H), 7.57–7.54 (m, 3H), 7.22 (dd, J = 8.0, 1.6 Hz, 1H), 7.10–7.06 (m, 2H), 4.89 (dd, J = 170.4, 14.8 Hz, 2H), 3.74 (s, 3H), 1.34 (s, 9H); 13C-NMR (100 MHz, CDCl3) δ 165.2, 157.1, 148.2, 141.6, 140.7, 133.9, 132.7, 132.0, 121.6, 120.9, 114.8, 111.9, 83.6, 55.8, 50.3, 27.9; MS-ESI (m/z): calcd. for C20H23N4O3 [M + H]+ 367.2, found 367.2.
tert-Butyl 2-(5-(2-methylphenyl)-4-(pyridin-4-yl)-1H-1,2,3-triazol-1-yl)acetate. White solid; 1H-NMR (400 MHz, CDCl3) δ 8.50 (brs, 2H), 7.50–7.47 (m, 3H), 7.39–7.34 (m, 2H), 7.25 (d, J = 6.8 Hz, 1H), 4.81(dd, J = 103.6, 17.2 Hz, 2H), 2.00 (s, 3H), 1.36 (s, 9H); 13C-NMR (100 MHz, CDCl3) δ 165.1, 149.4, 141.5, 139.5, 138.1, 135.9, 131.4, 131.0, 130.2, 127.0, 125.9, 120.1, 83.8, 49.8, 27.9, 19.5; MS-ESI (m/z): calcd. for C20H23N4O2 [M + H]+ 351.2, found 351.2.
tert-Butyl 2-(5-(naphthalen-1-yl)-4-(pyridin-4-yl)-1H-1,2,3-triazol-1-yl)acetate. White solid; 1H-NMR (400 MHz, CDCl3) δ 8.40 (brs, 2H), 8.09 (d, J = 8.0 Hz, 1H), 7.98 (d, J = 8.4 Hz, 1H), 7.62–7.50 (m, 3H), 7.43–7.40 (m, 3H), 7.33 (d, J = 8.4 Hz, 1H), 4.76 (dd, J = 159.6, 17.2 Hz, 2H), 1.28 (s, 9H); 13C-NMR (100 MHz, CDCl3) δ 165.2, 149.3, 142.6, 139.0, 134.8, 133.9, 131.4, 129.3, 129.0, 128.1, 127.3, 125.6, 124.4, 123.6, 120.5, 110.1, 83.8, 50.0, 27.8; MS-ESI (m/z): calcd. for C23H23N4O2 [M + H]+ 387.2, found 387.2.
tert-Butyl 2-(5-phenyl-4-(pyridin-3-yl)-1H-1,2,3-triazol-1-yl)acetate. White solid; 1H-NMR (400 MHz, CDCl3) δ 8.70 (d, J = 2.2 Hz, 1H), 8.49 (dd, J = 4.9, 1.7 Hz, 1H), 8.04 (dt, J = 8.0, 1.9 Hz, 1H), 7.57–7.48 (m, 3H), 7.37–7.32 (m, 2H), 7.29 (dd, J = 7.9, 5.0 Hz, 1H), 4.91 (s, 2H), 1.40 (s, 9H); 13C-NMR (100 MHz, CDCl3) δ 165.5, 148.9, 147.8, 141.6, 135.2, 134.0, 130.3, 129.8, 129.6, 127.0, 126.8, 123.5, 83.7, 50.1, 27.9; MS-ESI (m/z): calcd. for C19H21N4O2 [M + H]+ 337.2, found 337.2.
tert-Butyl 2-(5-phenyl-4-(pyridin-2-yl)-1H-1,2,3-triazol-1-yl)acetate. White solid; 1H-NMR (400 MHz, CDCl3) δ 8.48 (d, J = 4.6 Hz, 1H), 7.80 (d, J = 7.9 Hz, 1H), 7.67 (t, J = 7.8 Hz, 1H), 7.51–7.44 (m, 3H), 7.42–7.37 (m, 2H), 7.19–7.11 (m, 1H), 4.93 (s, 2H), 1.39 (s, 9H); 13C-NMR (100 MHz, CDCl3) δ 165.5, 150.5, 149.5, 144.2, 136.4, 136.3, 130.1, 129.7, 128.8, 127.4, 122.4, 121.7, 83.5, 50.1, 27.8; MS-ESI (m/z): calcd. for C19H21N4O2 [M + H]+ 337.2, found 337.2.
tert-Butyl 2-(4,5-diphenyl-1H-1,2,3-triazol-1-yl)acetate. White solid; 1H-NMR (400 MHz, CDCl3) δ 7.57 (d, J = 7.4 Hz, 2H), 7.54–7.44 (m, 3H), 7.35 (d, J = 7.1 Hz, 2H), 7.29–7.27 (m, 2H), 4.90 (s, 2H), 1.40 (s, 9H); 13C-NMR (100 MHz, CDCl3) δ 165.6, 144.4, 134.5, 130.9, 130.0, 130.0, 129.4, 128.5, 127.8, 127.6, 126.9, 83.5, 50.1, 27.9; MS-ESI (m/z): calcd. for C20H22N3O2 [M + H]+ 336.2, found 336.2.
tert-Butyl 2-(4-(4-methoxyphenyl)-5-phenyl-1H-1,2,3-triazol-1-yl)acetate. Orange solid; 1H-NMR (400 MHz, CDCl3) δ 7.55–7.44 (m, 5H), 7.34 (dd, J = 7.4, 2.1 Hz, 2H), 6.81 (d, J = 8.7 Hz, 2H), 4.89 (s, 2H), 3.78 (s, 3H), 1.39 (s, 9H); 13C-NMR (100 MHz, CDCl3) δ 165.8, 159.4, 144.4, 133.8, 130.1, 129.9, 129.4, 128.3, 127.8, 123.6, 114.0, 83.5, 55.3, 50.1, 28.0; MS-ESI (m/z): calcd for C21H24N3O3 [M + H]+ 366.2, found 366.2.
tert-Butyl 2-(5-phenyl-4-(2-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-1-yl)acetate. Red solid; 1H-NMR (400 MHz, CDCl3) δ 7.72 (dd, J = 6.2, 3.0 Hz, 1H), 7.52–7.42 (m, 2H), 7.40–7.28 (m, 4H), 7.24–7.16 (m, 2H), 5.02 (s, 2H), 1.40 (s, 9H); 13C-NMR (100 MHz, CDCl3) δ 165.5, 143.1, 136.3, 133.3, 131.9, 131.5, 129.7, 129.5, 129.0, 128.9, 126.6 (q, J = 5.1 Hz), 126.5, 125.2, 122.5, 83.7, 50.6, 27.9; MS-ESI (m/z): calcd. for C21H21F3N3O2 [M + H]+ 404.2, found 404.2.
tert-Butyl 2-(5-phenyl-4-(pyridin-4-yl)-1H-1,2,3-triazol-1-yl)propanoate. Yellow solid; 1H-NMR (400 MHz, CDCl3) δ 8.52 (s, 2H), 7.82 (s, 2H), 7.72–7.61 (m, 2H), 7.58–7.47 (m, 1H), 7.36 (d, J = 6.8 Hz, 1H), 4.83 (q, J = 7.3 Hz, 1H), 1.91 (d, J = 7.3 Hz, 3H), 1.41 (s, 9H); 13C-NMR (100 MHz, CDCl3) δ 168.1, 150.1, 141.6, 138.6, 136.0, 130.6, 130.0, 129.8, 127.1, 120.7, 83.4, 57.1, 27.9, 17.0; MS-ESI (m/z): calcd. for C20H23N4O2 [M + H]+ 351.2, found 351.2.
tert-Butyl 2-(5-phenyl-4-(pyridin-4-yl)-1H-1,2,3-triazol-1-yl)butanoate. White solid; 1H-NMR (400 MHz, CDCl3) δ 8.52 (s, 2H), 7.89 (s, 2H), 7.77–7.61 (m, 3H), 7.40–7.31 (m, 2H), 4.58 (dd, J = 10.7, 4.7 Hz, 1H), 2.51 (ddq, J = 14.5, 10.6, 7.3 Hz, 1H), 2.34 (dqd, J = 14.7, 7.4, 4.6 Hz, 1H), 1.42 (s, 9H), 0.91 (t, J = 7.4 Hz, 3H); 13C-NMR (100 MHz, CDCl3) δ 167.6, 150.2, 141.4, 138.6, 136.7, 130.6, 130.1, 129.8, 127.2, 120.7, 83.3, 63.0, 28.0, 24.2, 10.9; MS-ESI (m/z): calcd. for C21H25N4O2 [M + H]+ 365.2, found 365.2.

Acknowledgments

We thank National Institutes of Health (NIGMS R01-GM079554), the Welch Foundation (I-1868), Cancer Prevention and Research Institute of Texas (RP130212), and UT Southwestern for financial support.

Author Contributions

Chengwei Zhang , Lin You and Chuo Chen conceived and designed the experiments; Chengwei Zhang and Lin You performed the experiments; Chengwei Zhang , Lin You and Chuo Chen analyzed the data; Chuo Chen wrote the paper.

Conflicts of Interest

The authors declare no conflict of interest.

Abbreviations

The following abbreviations are used in this manuscript:
Cy-JohnPhos
(2-Biphenyl)dicyclohexylphosphine
dba
dibenzylideneacetone
DMF
N,N-Dimethylformamide
DMSO
Dimethyl sulfoxide
NMP
N-Methylpyrrolidine

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  • Sample Availability: Samples of the compounds 4 are available from the authors.
Table 1. Optimization of palladium-catalyzed C–H arylation of 1.
Table 1. Optimization of palladium-catalyzed C–H arylation of 1.
Molecules 21 01268 i001
EntryCatalystLigandBaseTemperatureTimeSolventYield
1CuIt-BuLi120 °C24 hDMF10% a
2Pd(OAc)2n-Bu4NOAc120 °C24 hNMP15% a
3Pd(OAc)2n-Bu4NOAc120 °C20 hDMF21% a
4Pd(OAc)2Cs2CO3120 °C20 hDMF6% a
5Pd(OAc)2K2CO3120 °C20 hDMF31% a
6Pd(OAc)2PPh3K2CO3120 °C20 hDMF75% a 68% b
7Pd(OAc)2P(o-Tol)3K2CO3120 °C20 hDMF70% a
8Pd(OAc)2PPh3K2CO3100 °C24 hDMF77% a
9Pd(OAc)2P(n-Bu)3K2CO3100 °C24 hDMF<5% a
10Pd(OAc)2PCy3K2CO3100 °C24 hDMF20% a
11Pd(OAc)2P(2-furyl)3K2CO3100 °C24 hDMF29% a
12Pd(OAc)2Cy-JohnPhosK2CO3100 °C24 hDMF19% a
13Pd2(dba)3 cK2CO3100 °C24 hDMF7% a
14Pd(OAc)2PPh3K2CO3120 °C20 htoluene95% a 89% b
a Estimated by HPLC; b Isolated yield; c 5 mol % catalyst.
Table 2. Scope of palladium-catalyzed C–H arylation of triazoles.
Table 2. Scope of palladium-catalyzed C–H arylation of triazoles.
Molecules 21 01268 i002
EntryAr1Ar2RYield
14-pyridylphenylH89%
24-pyridyl4-MeO-phenylH85%
34-pyridyl4-EtO2C-phenylH92%
44-pyridyl4-F3C-phenylH83%
54-pyridyl4-NC-phenylH79%
64-pyridyl4-F-phenylH51%
74-pyridyl3-Me-phenylH86%
84-pyridyl3-OHC-phenylH32%
94-pyridyl2-MeO-phenylH82%
104-pyridyl2-Me-phenylH49%
114-pyridyl1-naphthylH78%
124-pyridylphenylH80%
134-pyridylphenylH84%
14phenylphenylH80%
154-MeO-phenyllphenylH64%
162-F3C-phenylphenylH50%
174-pyridylphenylMe20% a
184-pyridylphenylEt8% a
a Microwave heating, 140 °C, 15 min.
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