8-Hydroxyquinoline (quinolin-8-ol) ring system provides a promising structural motif for the design of new pharmaceutical compounds.1 For example, a series of 8-hydroxyquinoline derivatives have been characterized with regard to their antimicrobial,2 antiviral,3 and anticancer4 activity. Clioquinol (5-chloro-7-iodoquinolin-8-ol) is used as active pharmaceutical ingredient in topical medications for the treatment of bacterial and fungal skin infections.5 It is known that the ions of certain metals (iron, copper, zinc, aluminum) play an important role in the development of neurodegenerative conditions.6 The development of such diseases can be slowed by using chelate-forming molecules, in particular 8-hydroxyquinoline derivatives.7 Coordination compounds of 8-hydroxyquinoline and its derivatives, for example, aluminum 8-hydroxyquinolinate, are widely used in the design of devices on the basis of organic light-emitting diodes (OLED).8 A traditional application of 8-hydroxyquinoline and some of its substituted analogs has been in analytical chemistry for qualitative and quantitative determination of various metal ions.9 Compounds of such structure are also commonly used in the design of fluorescent and colorimetric chemical sensors.10 The wide range of practical applications show that there is a substantial need for developing new methods for the modification of 8-hydroxyquinoline ring system.

In the current work, we propose an approach that relies of the N-amination of 8-hydroxyquinoline, followed by modification of cation in N-aminoquinolinium salt 1 (Scheme 1). A convenient N-aminating reagent for this purpose is О-(mesitylenesulfonyl)hydroxylamine (MSH).11 The N-amino cations formed by amination of azines are deprotonated at the NH group even in the presence of a weak base, giving the respective N-imides (azanides), which actively participate in 1,3-dipolar cycloaddition reactions. Suitable dipolarophiles include alkynes bearing electron-withdrawing groups, as well as alkenes or nitriles.12

scheme 1

Scheme 1

At the first stage of our work, we studied the reaction of mesitylenesulfonate 1 with acetylenes containing electronwithdrawing substituents in the presence of a base (Scheme 1). Such reactions have been thoroughly studied for pyridine N-imides and can be used to obtain pyrazolo-[1,5-а]pyridines in moderate to good yields.12,13 The reactions of quinoline and isoquinoline N-amino derivatives, as well as other benzo-fused azines with alkynes resulted in only moderate yields of the respective pyrazolo[1,5-а]azines.14

The reactions of N-amino-8-hydroxyquinolinium salt 1 with acetylenes containing electron-withdrawing substituents gave high yields of products 2b,с (Scheme 2). The best results were achieved by using K2СО3 as a base and МеCN as a solvent. However, the preparation of product 2а was complicated by a side reaction where dimethyl acetylenedicarboxylate (DMAD) added at the hydroxy group, resulting in the formation of product 2а' in 15% yield (Scheme 3). This observation can be explained by the substantially higher electrophilicity of DMAD compared to other acetylenes. The double bond geometry (E or Z) of compound 2а' was not established, since it was found to be unstable. The structure was proposed on the basis of 1Н NMR and high-resolution mass spectral data.

scheme 2

Scheme 2

scheme 3

Scheme 3

A research group from India has previously demonstrated that alkenes containing a carbonyl or carboxy group at the double bond effectively reacted with pyridine N-imides in N-methylpyrrolidone (NMP) medium in the absence of a base, resulting in the formation of pyrazolo-[1,5-a]pyridines in high yields.15 Taking into account the fact that alkenes containing electron-withdrawing groups are affordable and readily available compounds, we decided to apply this method for the preparation of pyrazolo[1,5-a]quinolin-9-ols. However, performing the reaction of mesitylenesulfonate 1 with benzalacetone in NMP did not result in the formation of product in even trace amounts, with only the starting ketone recovered. The addition of a base (K2СО3 or DBU) led to the formation of product 2d in small amounts (Scheme 4). Further optimization of reaction conditions allowed to establish that our previously used K2CO3–MeCN system was the most effective option.

scheme 4

Scheme 4

Reactions with dimethyl fumarate or maleate gave product 2а in equal yields. Ethyl acrylate and methyl cinnamate led to the formation of pyrazoloquinolines 2b,c, respectively, in moderate yields that were lower than obtained from reactions of salt 1 with the respective acetylenes. Remarkably, performing this reaction with alkenes containing a carbonyl group led to substantially higher yields (Scheme 4, products 2d–f). This could be explained by the stronger electron-withdrawing effect of carbonyl group compared to a carboxy group.

The reaction mechanism apparently included deprotonation of mesitylenesulfonate 1 with the formation of N-imide 1', which further participated in 1,3-cycloaddition reaction with alkenes containing electronwithdrawing groups (Scheme 5). The subsequent oxidation of cycloadduct 3 with air oxygen led to the reaction products 2a–f. Studying the reaction mixtures with 1Н NMR spectroscopy did not reveal the signals of hydrogenated derivatives 3, indicating that the oxidation reaction occurred rapidly. The addition of oxidants such as chloranil or DDQ had no significant effect on the yields of products 2a–f (Scheme 5).

scheme 5

Scheme 5

It is known that nitriles also participate in cycloaddition reactions with pyridinium N-imines, resulting in the formation of [1,2,4]triazolo[1,5-а]pyridines.12,16 We have previously used the reaction of salt 1 with 2-cyanopyridine for the synthesis of 2-(2-pyridyl)[1,2,4]triazolo[1,5-а]-quinolin-9-ol that was characterized regarding its ability to coordinate with rhenium.17 In this work, we set out to study the reaction of mesitylenesulfonate 1 with aliphatic and aromatic nitriles. The reaction with an excess of MeCN in 2 N KОН solution produced 2-methylpyrazoloquinoline 4а (Scheme 6). However, the attempts to perform this reaction with other aliphatic nitriles, such as propionitrile, butyronitrile, isobutyronitrile, and pivalonitrile, were not successful. It is also interesting to note that, although the reaction of salt 1 with acetonitrile readily occurred in aqueous alkali solutions, this reaction did not proceed in pure acetonitrile.

scheme 6

Scheme 6

The reactions with benzonitrile, phthalodinitrile, and 3,4-dimethoxybenzonitrile gave moderate yields of products 4b–d, respectively. However, 4-hydroxy-3-methoxybenzonitrile did not participate in the reaction, apparently due to the deprotonation of ОН group, which markedly reduced the reactivity of this dipolarophile.

The molecular structures of the obtained compounds were confirmed by data of 1Н and 13С NMR spectroscopy. For all of the described compounds, 1Н NMR spectra featured an ОН signal in the chemical shift range of 10.5–12.0 ppm. The characteristic signals of AB system consisting of Н-4,5 protons were also present, with coupling constants of 9.4–9.5 Hz. It should be noted that the value of spin-spin coupling constant did not differ depending on the presence of pyrazole or triazole ring fused with the quinoline nucleus. The spectra of all compounds contained signals of АВС system consisting of H-6,7,8 protons with the characteristic spin-spin coupling constants of 7.8–7.9 Hz between vicinal protons, while in some cases also coupling between the H-6 and H-8 protons was observed, with spin-spin coupling constants of 1.3–1.4 Hz.

The spin-spin coupling constant between Н-5 and Н-6 protons in the spectrum of compound 4b was 0.4 Hz, which was used for the assignment of signals. The positions of substituents in the molecule of compound 2с were determined from NOE signals that were observed between the protons of OCH3 group and the Н-4 and Н-2',6' Ph protons (Fig. 1).

Figure 1.
figure 1

The observed NOE signals in the molecule of compound 2с.

Full size image

IR spectra of all obtained compounds featured an absorption band due to the stretching vibrations of О–Н group. The spectra of compounds 2а–с contained a С=О absorption band in the range of 1709–1714 cm–1, which is characteristic for the ester groups. In the case of products 2d–f, the С=О absorption band was observed in the range of 1637–1671 cm–1, as expected for ketone carbonyl groups. Furthermore, IR spectrum of compound 4c showed an abosorption band at 2220 cm–1, corresponding to CN group. Mass spectra of all compounds showed molecular ion peaks that matched the calculated values. Purity was confirmed by the results of elemental analysis.

Thus, we have studied the reactions of 1-amino-8-hydroxyquinolinium mesitylenesulfonate in the presence of base with various types of dipolarophiles: alkynes and alkenes containing electron-withdrawing groups, as well as with nitriles. Both the reactions with alkynes and alkenes led to the formation of the respective pyrazolo[1,5-а]-quinolin-9-ol derivatives in moderate to good yields. It was shown that suitable electron-withdrawing substituents in the alkene molecule included CO2R, COMe, and COPh groups. We also demonstrated that 2-substituted [1,2,4]triazolo[1,5-а]quinolin-9-ols can be obtained by reactions of 1-amino-8-hydroxyquinolinium salt with acetonitrile and aromatic nitriles. At the same time, other aliphatic nitriles did not participate in similar reactions.

Experimental

IR spectra were recorded on a Bruker Vector 22 FT-IR spectrometer for samples in KВr pellets. 1Н NMR spectra were acquired on a Bruker AV-400 instrument (400 MHz), 13С NMR spectra – on a Bruker AV-300 instrument (75 MHz). The residual signals of CDCl3 solvent were used as internal standard (7.26 ppm for 1Н nuclei and 77.16 ppm for 13С nuclei). High-resolution mass spectra were recorded on a DFS Thermo Electron instrument, using EI ionization (70 eV). Melting points were determined on a Kofler bench. Column chromatography was performed on neutral alumina (Reakhim, pure grade, specification (TU) 6-09-3916-75) or silica gel 60 from Macherey–Nagel (0.040–0.060 mm). The reaction progress was controlled by TLC on Sorbfil silica gel plates, visualization under UV light.

8-Hydroxyquinoline, nitriles, acetylenes, and alkenes were purchased from commercial sources and were used without additional purification. 1-Amino-8-hydroxyquinolinium mesitylenesulfonate was obtained from О-mesitylenesulfonylhydroxylamine10 according to previously reported procedures.15 MeCN was distilled from P2O5 and stored over 4 Å molecular sieves.

Dimethyl 9-hydroxypyrazolo[1,5-а]quinoline-2,3-dicarboxylate (2а). A solution of DMAD (44 mg, 0.31 mmol) in MeCN (4 ml) was added to a solution of salt 1 (112 mg, 0.31 mmol) in MeCN (2 ml). The stirred solution was then treated by adding K2CO3 (1.55 mmol) in a single portion. The obtained mixture was further stirred for 24 h, then diluted with water (20 ml), adjusted with 2 N HCl to neutral pH, and extracted with CH2Cl2 (3×10 ml). The extract was dried over anhydrous Na2SO4, and the solvent was removed by evaporation on a rotary evaporator. The obtained mixture was separated by silica gel column chromatography, using CH2Cl2 as eluent, Rf 0.62. Yield 47 mg (50%), pale-yellow crystals, mp 149–150°С (EtOH). IR spectrum, ν, cm–1: 3430 (ОН), 1714 (CO). 1H NMR spectrum, δ, ppm (J, Hz): 3.93 (3H, s, OСН3); 4.02 (3H, s, OСН3); 7.24 (1Н, dm, J = 8.0, H-6(8)); 7.29 (1Н, dm, J = 7.9, H-8(6)); 7.41 (1Н, t, J = 8.0, H-7); 7.68 (1Н, d, J = 9.5, Н-4(5)); 7.93 (1Н, d, J = 9.5, Н-5(4)); 11.15 (1Н, s, OH). 13C NMR spectrum, δ, ppm: 52.1 (CH3); 53.3 (CH3); 104.5; 116.4; 117.3; 118.9; 121.8; 125.9; 127.7; 130.5; 139.5; 144.0; 148.8; 162.6 (2CO). Found, m/z: 300.0744 [М]+. C15H12N2O5. Calculated, m/z: 300.0741. Found, %: С 60.25; Н 3.91; N 9.30. C15H12N2O5. Calculated, %: С 60.00; Н 4.03; N 9.33.

Compound 2а was also obtained under analogous conditions from dimethyl fumarate or dimethyl maleate (45 mg, 0.31 mmol). Yield 52 mg (55%).

Further elution yielded a compound that was identified as dimethyl 9-[(1,4-dimethoxy-1,4-dioxobut-2-en-2-yl)-oxy]pyrazolo[1,5-а]quinoline-2,3-dicarboxylate (2а'). Rf 0.19. Yield 20 mg (15%), yellow oil. 1H NMR spectrum, δ, ppm (J, Hz): 3.59 (3H, s, OСН3); 3.92 (3H, s, OСН3); 3.96 (3H, s, OСН3); 4.01 (3H, s, OСН3); 4.83 (1H, s, CH); 7.51 (1Н, dd, J = 7.9, J =1.5, H-6(8)); 7.57 (1Н, t, J = 7.8, H-7); 7.72 (1Н, d, J = 9.4, H-4(5)); 7.79 (1Н, dd, J = 7.8, J = 1.5, H-8(6)); 8.13 (1Н, d, J = 9.4, H-5(4)). Found, m/z: 442.1009 [М]+. C21H18N2O9. Calculated, m/z: 442.1007.

Ethyl 9-hydroxypyrazolo[1,5-а]quinoline-3-carboxylate (2b) was obtained analogously to the procedure for the preparation of compound 2а from ethyl propiolate (31 mg, 0.31 mmol). Rf 0.68 on silica gel sorbent with CH2Cl2 as eluent. Yield 61 mg (77%), beige crystals, mp 214–215°С (EtOH). IR spectrum, ν, cm–1: 3432 (OH), 1709 (CO). 1H NMR spectrum, δ, ppm (J, Hz): 1.43 (3H, t, J = 7.8, CH3); 4.40 (2Н, q, J = 7.8, CH2); 7.24 (1Н, dm, J = 7.9, H-6(8)); 7.29 (1Н, dm, J = 7.9, H-6(8)); 7.39 (1Н, t, J = 7.9, H-7); 7.67 (1Н, d, J = 9.4, Н-4(5)); 8.00 (1Н, d, J = 9.4, Н-5(4)); 8.36 (1Н, s, Н-2); 11.70 (1Н, br. s, ОН). 13C NMR spectrum, δ, ppm: 14.6; 60.5; 105.7; 116.4; 116.7; 118.6; 122.4; 125.5; 126.9; 129.7; 138.7; 141.1; 148.9; 163.3. Found, m/z: 256.0847 [М]+. C14H12N2O3. Calculated, m/z: 256.0842. Found, %: С 65.87; Н 4.68; N 10.99. C14H12N2O3. Calculated, %: С 65.62; Н 4.72; N 10.93.

Compound 2b was also obtained under analogous conditions from ethyl acrylate (32 mg, 0.31 mmol). Yield 50 mg (63%).

Methyl 9-hydroxy-2-phenylpyrazolo[1,5-а]quinoline-3-carboxylate (2c) was obtained from methyl 3-phenylpropiolate (54 mg, 0.31 mmol) analogously to the procedure for the preparation of compound 2а. Rf 0.60 on silica gel sorbent with CH2Cl2 as eluent. Yield 91 mg (92%), beige crystals, mp 172–173°С (EtOH). IR spectrum, ν, cm–1: 3432 (OH), 1714 (CO). 1H NMR spectrum, δ, ppm (J, Hz): 3.86 (3H, s, OCH3); 7.24 (1Н, dm, J = 7.9, H-6(8)); 7.30 (1Н, dm, J = 7.9, H-8(6)); 7.40 (1Н, t, J = 7.9, H-7); 7.46–7.51 (3Н, m, H-3,4,5 Ph); 7.68 (1Н, d, J = 9.5, H-4(5)); 7.77–7.82 (2Н, m, H-2,6 Ph); 8.05 (1Н, d, J = 9.5, H-5(4)); 11.83 (1Н, br. s, ОН). 13C NMR spectrum δ, ppm: 51.5; 102.4; 116.7; 116.9; 118.6; 122.1; 125.5; 126.9; 128.1; 129.4; 129.6; 130.0; 131.7; 140.5; 148.9; 153.5; 163.9. Found, m/z: 318.1006 [М]+. C19H14N2O3. Calculated, m/z: 318.0999. Found, %: С 71.85; Н 4.40; N 8.85. C19H14N2O3. Calculated, %: С 71.69; Н 4.43; N 8.80.

Compound 2с was also obtained under analogous conditions from methyl cinnamate (55 mg, 0.31 mmol). Yield 51 mg (51%).

1-(9-Hydroxy-2-phenylpyrazolo[1,5-а]quinolin-3-yl)ethan-1-one (2d) was obtained analogously to the procedure for the preparation of compound 2а from benzalacetone (46 mg, 0.31 mmol). Rf 0.65 on silica gel sorbent with CH2Cl2 as eluent. Yield 83 mg (88%), white crystals, mp 134–135°С (EtOH). IR spectrum, ν, cm–1: 3431 (OH), 1651 (C=O). 1H NMR spectrum, δ, ppm (J, Hz): 2.18 (3H, s, CH3); 7.27 (1Н, dm, J = 7.7, H-6(8)); 7.36 (1Н, dm, J = 7.8, H-8(6)); 7.45 (1Н, t, J = 7.8, H-7); 7.52–7.60 (3Н, m, H-3,4,5 Ph); 7.60–7.67 (2Н, m, H-2,6 Ph); 7.75 (1Н, d, J = 9.4, H-4(5)); 8.27 (1Н, d, J = 9.5, H-5(4)); 11.80 (1Н, br. s, ОН). 13C NMR spectrum δ, ppm (J, Hz): 30.6; 112.9; 116.7; 117.3; 118.6; 121.9; 126.0; 127.0; 128.7; 129.7; 130.0; 130.5; 132.6; 139.8; 148.9; 153.1; 194.4. Found, m/z: 302.1049 [М]+. C19H14N2O2. Calculated, m/z: 302.1050. Found, %: С 75.61; Н 4.55; N 9.20. C19H14N2O2. Calculated, %: С 75.48; Н 4.67; N 9.27.

1-(9-Hydroxypyrazolo[1,5-а]quinolin-3-yl)ethan-1-one (2e) was obtained analogously to the procedure for the preparation of compound 2а from methyl vinyl ketone (22 mg, 0.31 mmol). Rf 0.61 on silica gel sorbent with CHCl3 as eluent. Yield 60 mg (85%), white crystals, mp 145–146°С (EtOH). IR spectrum, ν, cm–1: 3430 (OH), 1671 (C=O). 1H NMR spectrum, δ, ppm (J, Hz): 2.58 (3H, s, CH3); 7.23 (1Н, d, J = 7.9, H-6(8)); 7.28 (1Н, d, J = 7.9, H-8(6)); 7.40 (1Н, t, J = 7.9, H-7); 7.68 (1Н, d, J = 9.4, H-4(5)); 8.15 (1Н, d, J = 9.5, H-5(4)); 8.28 (1Н, s, H-2); 11.64 (1Н, s, ОН). 13C NMR spectrum δ, ppm: 28.4; 114.1; 116.7; 116.9, 118.6; 122.1; 125.8; 127.1; 130.5; 138.0; 140.8; 148.9; 192.2. Found, m/z: 226.0744 [М]+. C13H10N2O2. Calculated, m/z: 226.0737. Found, %: С 69.31; Н 4.50; N 12.27. C13H10N2O2. Calculated, %: С 69.02; Н 4.46; N 12.38.

(9-Hydroxy-2-phenylpyrazolo[1,5-а]pyridin-3-yl)(phenyl)-methanone (2f) was obtained analogously to the procedure for the preparation of compound 2а from benzalacetophenone (65 mg, 0.31 mmol). Rf 0.63 on silica gel sorbent CHCl3 as eluent. Yield 103 mg (91%), white crystals, mp 131–132°С (EtOH). IR spectrum, ν, cm–1: 3435 (OH), 1637 (C=O). 1H NMR spectrum, δ, ppm (J, Hz): 7.16–7.25 (7Н, m, H Ar); 7.30–7.37 (2Н, m, H Ar); 7.45–7.49 (2Н, m, H Ar); 7.56 (1Н, d, J = 9.4, H-4(5)); 7.62–7.66 (2Н, m, H Ar); 7.68 (1Н, d, J = 9.4, H 5(4)); 11.85 (1Н, s, ОН). 13C NMR spectrum, δ, ppm: 110.8; 116.2; 116.5; 118.5; 121.9; 125.5; 126.7; 128.1; 128.2; 128.8; 129.3; 129.5; 129.6; 131.4; 132.3; 138.6; 140.5; 148.7; 152.4; 191.0. Found, m/z: 364.1210 [М]+. C24H16N2O2. Calculated, m/z: 364.1206. Found, %: С 79.26; Н 4.39; N 7.74. Calculated, %: С 79.11; Н 4.43; N 7.69.

2-Methyl[1,2,4]triazolo[1,5-а]quinolin-9-ol (4a). Salt 1 (100 mg, 0.28 mmol) was dissolved in aqueous 2 N KOH solution (5 ml). MeCN (0.5 ml) was added to the obtained mixture, and stirring was continued until the yellow color faded. The mixture was then neutralized with 2 N HCl solution and extracted with CHCl3 (3×10 ml). The extract was dried over anhydrous Na2SO4 and evaporated. The product was purified by column chromatography on alumina, using 100:1 CH2Cl2–MeOH mixture as eluent, Rf 0.71. Yield 35 mg (63%), yellowish crystals, mp 133–135°С (EtOH–hexane, 1:2). 1H NMR spectrum, δ, ppm (J, Hz): 2.64 (3Н, s, СН3); 7.22 (1Н, dm, J = 7.8, H-6(8)); 7.30 (1Н, dm, J = 7.9, H-8(6)); 7.32–7.44 (1Н, m, J = 7.9, H-7); 7.50 (1Н, d, J = 9.5, H-4(5)); 7.76 (1Н, d, J = 9.5, H-5(4)); 10.90 (1Н, s, ОН). 13C NMR spectrum, δ, ppm: 14.5; 114.4; 116.3; 118.9; 122.0; 124.8; 126.8; 131.8; 147.7; 149.2; 161.2. Found, m/z: 199.0743 [М]+. C11H9N3O. Calculated, m/z: 199.0740. Found, %: С 66.00; Н 4.56; N 21.09. C11H9N3O. Calculated, %: С 66.32; Н 4.55; N 21.09.

2-Phenyl[1,2,4]triazolo[1,5-а]quinolin-9-ol (4b). Salt 1 (200 mg, 0.56 mmol) was dissolved in aqueous 2 N KОН solution (5 ml). The obtained mixture was treated with a solution of benzonitrile (57 mg, 0.56 mmol) in EtOH (0.5 ml), and stirring was continued until the yellow color faded (approximately 24 h). The mixture was then neutralized with 2 N HCl solution and extracted with CHCl3 (3×10 ml). The extract was dried over anhydrous Na2SO4 and evaporated. The product was purified by column chromatography on alumina, using CH2Cl2 as eluent, Rf 0.65. Yield 81 mg (55%), pale-yellow crystals, mp 153–154°С (EtOH). 1H NMR spectrum, δ, ppm (J, Hz): 7.30 (1Н, ddd, J = 7.8, J = 1.3, J = 0.4, H-6); 7.38 (1Н, dd, J = 7.9, J = 1.3, H-8); 7.45 (1Н, t, J = 7.9, H-7); 7.46–7.55 (3Н, m, H Ph); 7.65 (1Н, d, J = 9.4, H-4); 7.84 (1Н, dd, J = 9.4, J = 0.4, H-5); 8.25–8.29 (2Н, m, H Ph); 11.06 (1Н, s, OH). 13C NMR spectrum δ, ppm: 114.7; 116.5; 119.1; 122.1; 125.0; 127.1; 127.4; 129.0; 130.0; 130.5; 132.2; 147.9; 149.8; 161.8. Found, m/z: 261.0905 [М]+. C16H11N3O. Calculated, m/z: 261.0897. Found, %: С 73.21; Н 3.98; N 16.25. C16H11N3O. Calculated, %: С 73.55; Н 4.24; N 16.08.

2-(9-Hydroxy[1,2,4]triazolo[1,5-а]quinolin-2-yl)benzonitril (4c) was obtained from phthalodinitrile (72 mg, 0.56 mmol) analogously to the procedure for the preparation of compound 4b. Rf 0.32 on silica gel sorbent, using CH2Cl2 as eluent. Yield 48 mg (30%), beige crystals, mp 235–236°С (EtOH). IR spectrum, ν, cm–1: 3211 (OH); 2220 (C≡N). 1H NMR spectrum, δ, ppm (J, Hz): 7.34 (1Н, dd, J = 7.9, J = 1.2, H-8(9)); 7.38 (1Н, dd, J = 7.8, J = 1.2, H-9(8)); 7.47 (1Н, t, J = 7.9, H-7); 7.57 (1Н, td, J = 7.6, J = 1.1, H Ar); 7.66 (1Н, d, J = 9.4, H-4(5)); 7.72–7.78 (1Н, m, H Ar); 7.83–7.92 (2Н, m, H Ar, H-5(4)); 8.49 (1Н, dd, J = 8.0, J = 1.1, H Ar); 10.78 (1Н, br. s, OH). 13C NMR spectrum, δ, ppm: 110.5; 114.5; 117.3; 119.2 (2C); 122.0; 125.2; 127.7; 129.7; 130.3; 132.1; 133.0; 133.2; 135.0; 147.9; 149.3; 158.8. Found, m/z: 286.0849 [М]+. C17H10N4O. Calculated, m/z: 286.0849. Found, %: С 71.03; Н 3.66; N 19.61. C17H10N4O. Calculated, %: С 71.32; Н 3.52; N 19.57.

2-(3,4-Dimethoxyphenyl)[1,2,4]triazolo[1,5-а]quinolin-9-ol (4d) was obtained from 3,4-dimethoxybenzonitrile (91 mg, 0.56 mmol) analogously to the procedure for preparation of compound 4b. Rf 0.62 on silica gel sorbent using 100:1 CHCl3–MeOH mixture as eluent. Yield 104 mg (58%), white crystals, mp 185–187°С (EtOH). 1H NMR spectrum, δ, ppm (J, Hz): 6.98 (1Н, d, J = 8.4, H-5' Ar); 7.28 (1Н, dd, J = 7.9, J = 1.4, H Ar); 7.37 (1Н, dd, J = 8.0, J = 1.4, H Ar); 7.43 (1Н, t, J = 7.9, H Ar); 7.62 (1Н, d, J = 9.4, H-4(5)); 7.75 (1Н, d, J = 2.0, H-2' Ar); 7.82 (1Н, d, J = 9.4, H-5(4)); 7.85 (1Н, dd, J = 8.4, J = 2.0, H-6' Ar); 11.09 (1H, s, OH). 13C NMR spectrum, δ, ppm (J, Hz): 56.2; 56.3; 110.3; 111.4; 114.6; 116.4; 119.1; 120.5; 122.2; 122.8; 125.0; 127.0; 132.0; 147.8; 149.5; 149.7; 151.2; 161.8. Found, m/z: 286.1109 [М]+. C18H15N3O3. Calculated, m/z: 321.1108. Found, %: С 67.45; Н 4.77; N 13.01. C18H15N3O3. Calculated, %: С 67.28; Н 4.71; N 13.08.

Supplementary information file containing 1Н and 13С NMR spectra of the obtained compounds is available at the journal website at http://springerlink.bibliotecabuap.elogim.com/journal/10593.