A convenient synthetic approach to polysubstituted dihydrogenated or heteroaromatic 1,2,4-triazolo- [1,5-a] pyrimidines derivatives containing at position 5 a 4-methylpyrimidine moiety bearing a cycloamino substituent at position 2 and linked to the triazolopyrimidine bicycle through its position 5 was developed. The approach involves unusual three-component condensations of 3-amino-1,2,4-triazoles, methyl 3-(2-R-4-methylpyrimidin- 5-yl)-3-oxopropionates, and a series of C1 synthons whose synthetic equivalents are a series of aromatic aldehydes, triethyl orthoformate, or DMFDMA were used as of C1 synthon

Ledeneva, I. V.

Paponov, B. V.

Polikarchuk, V. A.

Potapov, A. Yu.

Stolpovskaya, N. V.

DSpace at Belgorod State University

219ISSN 1070-4280, Russian Journal of Organic Chemistry, 2021, Vol. 57, No. 2, pp. 219–225. © Pleiades Publishing, Ltd., 2021.Russian Text © The Author(s), 2021, published in Zhurnal Organicheskoi Khimii, 2021, Vol. 57, No. 2, pp. 259–267.Three-Component Condencations of 3-Amino-1,2,4-triazoles, Methyl 3-(2-Cycloamino-4-methylpyrimidin-5-yl)-3-oxopropionoates, and a Series of C1 Synthons as a ConvenientApproach to Pyrimidin-5-yl-1,2,4-triazolo[1,5-a]pyrimidinesA. Yu. Potapova,*, V. A. Polikarchuka, B. V. Paponovb, I. V. Ledenevaa,N. V. Stolpovskayaa, D. V. Kryl’skiic, and Kh. S. Shikhalievaa Voronezh State University, Voronezh, 394006 Russiab Belgorod National Research University, Belgorod, 308015 Russiac Research Institute of Applied Acoustics, Dubna, 141981 Russia*e-mail: pistones@mail.ruReceived December 2, 2020; revised December 11, 2020; accepted December 14, 2020Abstract—A convenient synthetic approach to polysubstituted dihydrogenated or heteroaromatic 1,2,4-triazolo-[1,5-a]pyrimidines derivatives containing at position 5 a 4-methylpyrimidine moiety bearing a cycloamino sub-stituent at position 2 and linked to the triazolopyrimidine bicycle through its position 5 was developed. The approach involves unusual three-component condensations of 3-amino-1,2,4-triazoles, methyl 3-(2-R-4-me-thylpyrimidin-5-yl)-3-oxopropionates, and a series of C1 synthons whose synthetic equivalents are a series of aromatic aldehydes, triethyl orthoformate, or DMFDMA were used as of C1 synthons.Keywords: triazolopyrimidine, 4-methylpyrimidine, 1,3-ketocarboxylic acid ester, C1 synthon, three-component condensation, molecular hybridization, regioselectivityDOI: 10.1134/S1070428021020123INTRODUCTIONIn the context of the search for new hybrid multitarget molecules [1] containing fragments, one of which would have an antibacterial and the other an anticoagulant activity, we proposed to combine 1,2,4-triazolo[1,5-a]-pyrimidine and 2-cycloalkylamino-substituted pyri-midine scaffolds (Fig. 1).The fi rst components of the system I is a partially hydrogenated or heteroaromatic 1,2,4-triazolo[1,5-a]-pyrimidine bicycle I is interesting as a scaffold with pronounced antibacterial and anticancer properties [2]. Moreover, over the past years 1,2,4-triazolo[1,5-a]-pyrimidine derivatives have been considered as as promising reverse transcriptase inhibitors of a number of viruses [3]. The second component of the system II is a 2-cycloamino-4-methylpyrimidine fragment linked through its position 5 to position 5 of the triazolopyrimi-dine bicycle. Such scaffolds present interest primarily as an inhibitor of the endothelin converting enzyme 1 [4] and vascular adhesion protein [5], and, consequently, can be considered as quite promising scaffolds for the design of new anticoagulants. Furthermore, 2-cycloamino-4-methylpyrimidines can act as an activator of the insulin-like growth factor receptor [6] and an inhibitor of some phosphodiesterases [7].Three-component reactions of 1,3-dicarbonyl compounds with 3-amino-1,2,4-triazoles and aldehydes [8–12], orthoformates, or dimethylformamide dimethyl acetal (DMPDMA) [9, 13–15] are described in the literature and are convenient methods for the formation of polysubstituted triazolopyrimidine systems.RESULTS AND DISCUSSIONIn the present work we extended this approach to our earlier synthesized methyl 3-(2-R-4-methylpyrimidin-5-yl)-3-oxopropionates 1a and 1b, which were reacted with aromatic aldehydes 2a and 2b and 5-R-3-amino-1,2,4-triazoles 3a and 3b (Scheme 1). After prolonged RUSSIAN  JOURNAL  OF  ORGANIC  CHEMISTRY  Vol.  57  No.  2  2021220 POTAPOV  et  al.refl uxing of an equimolar mixture of the reagents in isopropanol or dioxane gives we isolated products4a–4d in yields of 48–64%. It was found that the nature of the solvent only slightly affects the yield and time of the reaction.The 1H NMR spectra of compounds 4a–4d contain signals of the aromatic protons of the aryl rings at 6.88–7.60 ppm and characteristic proton signals of the methoxycarbonyl groups at ~3.70 ppm. The NH and CH proton signals of the newly formed pyrimidine ring NNNNHNNNR1R2IIIOOCH3NNNNNNNR1R2IIIOOCH3 Fig. 1. Partially hydrogenated and heteroaromatic hybride 6-methoxyacrbonyl-7-(2-cycloamino-4-methylpyrimidin-5-yl)-2-R1-1,2,4-triazolo[1,5-a]pyrimidine molecules.Scheme 1.NNOOOCH3R1CH3ArCHONNNHR2 NH2+i-PrOH,refluxNNNR2NHAr OOCH3NNR1H3CNNOOOH3CR1H3CAri-PrOH, reflux48–64%NNOOOH3CR1H3CArNNNNH2R21a, 1b 2a, 2bAB4a–4d3a, 3bAr = C6H5 (2a, 4a, 4b), 4-CH3O-C6H4 (2b, 4c, 4d), R2 = H (3a, 4a, 4c), CH3 (3b, 4b, 4d).R1 =                    (1a, 4a, 4c);                         (1b, 4b, 4d);N NORUSSIAN  JOURNAL  OF ORGANIC  CHEMISTRY  Vol.  57  No.  2  2021221THREE-COMPONENT CONDENCATIONS OF 3-AMINO-1,2,4-TRIAZOLESappear at ~12.00 and 5.45 ppm, respectively. The proton signals of the triazole and pyrimidine rings are observed at 7.82 and 8.79 ppm, respectively. The mass spectra of compounds 4a–4d contain protonated molecular ion peaks. These data allow the synthesized products to be assigned the structure of methyl 5-(4-methyl-2-R-py-rimidin-5-yl)-7-aryl-4,7-dihidro[1,2,4]triazolo[1,5-a]-pyrimidine-6-carboxylates 4a–4d.We suggest that the reaction starts with a Knoevenagel-type condensation of esters 1 with alde-hydes to form intermediate arylidene derivatives A. The subsequent addition of the endocyclic NH group of aminotriazoles 3 at the C=C double bond of intermediate A leads to intermediate adduct B. The latter undergoes heterocyclization at the aminotriazole exocyclic amino group, yielding the fi nal pyrimidin-5-yltriazolo[1,5-a]-pyrimidines 4.Attempted synthesis by this three-component condensation of 7-unsubstituted esters of 5-(4-methyl-2-R-pyrimidin-5-yl)-4,7-dihydro[1,2,4]triazolo[1,5-a]-pyrimidine-6-carboxylic acids, with formaldehyde as the aldehyde component, failed. It was found that the main product of this reaction was compound 5 formed by the reaction of formaldehyde with two molecules of methyl 3-[4-methyl-2-(piperidin-1-yl)pyrimidin-5-yl]-3-oxopropionate (1c) (Scheme 2).The 1H NMR spectrum of compound 5 contains exclusively characteristic proton signals of methyl3-[4-methyl-2-(piperidin-1-yl)pyrimidin-5-yl]-3-oxo-propionate fragments tethered by a methylene group, the protons of which give two multiplets at 1.95–2.02 and 2.15–2.19 ppm. The mass spectral data, too, provide evidence for the proposed dimethyl 2,4-bis[4-methyl-2-(piperidin-1-yl)pyrimidin-5-ylcarbonyl]glutarate (5) structure (Fig. 2).With DMFDMA as an analog of the aldehyde component, the reactions of 3-(4-methyl-2-R-pyrimidin-5-yl)-3-oxopropionic acid esters 1a–1c and 5-amino-1,2,4-triazoles 3a–3c gave hardly separable mixtures of products. However, when the reactions were performed consecutively, we were able to direct the process to the formation of three-component reaction products, specifi cally methyl 7-(2-R-4-methylpyrimidin-5-yl)-2-R1-[1,2,4]triazolo[1,5-a]pyrimidine-6-carboxylates 6a–6e (Scheme 3).The 1H NMR spectra of compounds 6 display singlet signals of the methoxycarbonyl group protons at 3.65–3.78 ppm and proton signals of the newly formed pyrimidine ring at 8.82–9.39 ppm. In addition, the spectra show proton signals of the unsubstituted triazole ring (compounds 6a and 6c) at 8.24 ppm, and the spectra of the other derivatives show signals of the corresponding triazole substituents.Scheme 2.NNOOOCH3R1CH3+i-PrOHrefluxNNNHNH2OH HNNNNHOOCH3NNR1H3CNNOOOH3CR1CH3H2CNNO OOCH3R1CH3R1 = N5(1c, 5),3aRUSSIAN  JOURNAL  OF  ORGANIC  CHEMISTRY  Vol.  57  No.  2  2021222 POTAPOV  et  al.It can be assumed that enaminone B formed at the fi rst stage reacts with 5-aminotriazole with the elimination of dimethylamine, and, therewith, this reaction involves the most reactive exocyclic amino group of aminotriazole. Intermediate C formed at this stage undergoes cyclization into the fi nal product 6 via the reaction of the endocyclic amino and carbonyl groups, with the elimination of a water molecule.EXPERIMENTALThe 1H NMR spectra of the synthesized compounds were registered on a Bruker DRX-500 spectrometer (500 MHz) in DMSO-d6, internal reference TMS. The LC-MS analysis was performed on an Agilent Agilent 1260 Infi nity 6230 TOF LC/MS system with a dual ESI source, operated in the positive ion mode; nebulizer gas (N2) 20 psig, desiccant gas (N2) 6 mL/min, 325°C; mass range is 50–2000 Da. Capillary voltage 4.0 kV, fragmentor voltage +191 V, skimmer voltage +66 V, and OctRF voltage 750 V. Chromatography conditions: Poroshell 120 EC-C18 column (4.6×50 mm, 2.7 μm), gradient elution acetonitrile–water (0.1% formic acid), fl ow rate 0.4 mL/min. An Agilent MassHunter Data Acquisition Software (version B.06.00) was used for data processing. The melting points were measured on a Stuart SMP30 apparatus. The purity of reagents and synthesized compounds, as well as reaction progress were monitored by TLC on Merck Silica gel 60 F254 plates, eluent CHCl3–MeOH, 10 : 1 (spot development by exposure to UV light).The starting 3-(2-R-4-methylpyrimidin-5-yl)-3-oxopropionic acid esters 1a–1c were synthesized by the procedure described in our previous work [16].Methyl 5-(4-methyl-2-R-pyrimidin-5-yl)-7-aryl-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-6-car-boxylates 4a–4d (general procedure). A mixture of 4 mmol of ester 1a or 1b, 4 mmol of aldehyde 2a or 2b, and 4 mmol of 3-amino-1,2,4-triazole 3a or 3b was heated under refl ux in 5 mL ofi sopropanol for4 h. After cooling, a precipitate formed and was fi ltered off, washed with isopropanol, and recrystallized from isopropanol–DMF.Methyl 5-[4-methyl-2-(pyrrolidin-1-yl)pyrimidin-5-yl]-7-phenyl-4,7-dihydro[1,2,4]triazolo[1,5-a]-pyrimidine-6-carboxylate (4a). Yield 1.07 g (64%), fi ne white needles, mp 195–197°C. 1H NMR spectrum (DMSO-d6), δ, ppm: 1.49–1.55 m (4H, CH2CH2pyrrolid), 2.59 s (3H, CH3), 3.70 s (3H, CH3O), 3.81–3.92 m (4H, CH2NCH2), 5.45 s (1H, CH), 6.93 t (1Harom, J 7.8 Hz), 7.19–7.23 m (2Harom), 7.58–7.61 m (2Harom), 7.82 s (1H, Htriaz), 8.79 s (1H, Hpyrimid), 11.98 s (1H, NH). Mass spectrum, m/z: 418.1995 [M + H]+. C22H23N7O2. [M + H]+ 418.1987.0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 6 6.5, min*6.266×1054321Intensity ×10443210204.2398284.3263567.6435666.8104100 200 300 400 500 600 700 800 900 1000 1100m/z, DaIntensityFig. 2. HPLC–MS analysis of compound 5.RUSSIAN  JOURNAL  OF ORGANIC  CHEMISTRY  Vol.  57  No.  2  2021223THREE-COMPONENT CONDENCATIONS OF 3-AMINO-1,2,4-TRIAZOLESMethyl 2-methyl-5-[4-methyl-2-(morpholin-4-yl)pyrimidin-5-yl]-7-phenyl-4,7-dihydro[1,2,4]-triazolo[1,5-a]pyrimidine-6-carboxylate (4b). Yield 1.04 g (60%), fi ne white needles, mp 184–186°C. 1H NMR spectrum (DMSO-d6), δ, ppm: 2.06 s (3H, CH3), 2.59 s (3H, CH3), 3.70 s (3H, CH3O), 3.82 t (4H, CH2NCH2morph, J 8.2 Hz), 3.98 t (4H, CH2OCH2morph, J 8.2 Hz), 5.45 s (1H, CH), 6.95 t (1Harom, J 7.8 Hz), 7.22–7.25 m (2Harom), 7.57–7.61 m (2Harom), 8.79 s (1H, Hpyrimid), 11.98 s (1H, NH). Mass spectrum, m/z: 448.2098 [M + H]+. C23H25N7O3. [M + H]+ 448.2093.Methyl 7-(4-methoxyphenyl)-5-[4-methyl-2-(pyrrolidin-1-yl)pyrimidin-5-yl]-4,7-dihydro[1,2,4]-triazolo[1,5-a]pyrimidine-6-carboxylate (4c). Yield 0.86 g (48%), fi ne white needles, mp 189–191°C. 1H NMR spectrum (DMSO-d6), δ, ppm: 1.49–1.55 m (4H, CH2CH2pyrrolid), 2.59 s (3H, CH3), 3.60 s (3H, CH3O), 3.70 s (3H, CH3O), 3.81–3.92 m (4H, CH2NCH2),5.45 s (1H, CH), 6.91 d (2Harom, J 7.8 Hz), 7.21 d (2Harom, J 7.8 Hz), 7.82 s (1Htriaz), 8.79 s (1H, Hpyrimid), 11.98 s (1H, NH) Mass spectrum, m/z: 448.2088 [M + H]+. C23H25N7O3. [M + H]+ 448.2093.Methyl 7-(4-methoxyphenyl)-2-methyl-5-[4-methyl-2-(morpholin-4-yl)pyrimidin-5-yl]-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-6-carbo-xylate (4d). Yield 1.03 g (54%), fi ne white needles, mp 189–200°C. 1H NMR spectrum (DMSO-d6), δ, ppm: 2.05 s (3H, CH3), 2.59 s (3H, CH3), 3.60 s (3H, CH3O), Scheme 3.R1 =                     (1a, 6e);                         (1b, 6c, 6d);                       (1c, 6a, 6b);N NONNOOOCH3R1CH3DMFDMAi-PrOH,refluxNNOOOH3CR1H3CNCH3CH3NNNHR2 NH2i-PrOH,reflux–NH(CH3)2NNOOOH3CR1H3CHNNNNNOOCH3N NR1H3C –H2O44–71%NNNHR2R2N6a–6e1a–1cCDR2 = H (3a, 6a, 6c), C6H5 (3b, 6b, 6d), CH3S (3c, 6e).3a–3cRUSSIAN  JOURNAL  OF  ORGANIC  CHEMISTRY  Vol.  57  No.  2  2021224 POTAPOV  et  al.3.70 s (3H, CH3O), 3.81 t (4H, CH2NCH2morph, J8.2 Hz), 3.97 t (4H, CH2OCH2morph, J 8.2 Hz), 5.45 s (1H, CH), 6.90 d (2Harom, J 7.8 Hz), 7.20 d (2Harom, J 7.8 Hz), 8.78 s (1Hpyrimid), 11.97 s (1H, NH). Mass spectrum, m/z: 478.2194 [M + H]+. C24H27N7O4. [M + H]+ 478.2199.Dimethyl 2,4-bis{[4-methyl-2-(pyrrolidin-1-yl)-pyrimidin-5-yl]carbonyl}glutarate (5). A mixture of 4 mmol of methyl 3-[4-methyl-2-(pyrrolidin-1-yl)-pyrimidin-5-yl]-3-oxopropanoate 1c, 4 mmol of 40% formaldehyde, and 4 mmol of aminotriazole 3a was heated under refl ux in 5 mL of isopropanol for 2 h. After cooling, a precipitate formed and was fi ltered off and washed with isopropanol. Yield 1.03 g (54%), white amorphous material, mp 211–213°C. 1H NMR spectrum (DMSO-d6), δ, ppm: 1.49–1.71 m (12H, 2CH2CH2CH2piperid), 1.95–2.02 m (1H, CH2), 2.15–2.19 m (1H, CH2), 2.56 s (2H, 2CH3), 3.69 s (6H, 2CH3O), 3.80–3.94 m (8H, 2CH2NCH2), 5.14–5.16 m (2H, 2CH), 8.59 s (2H, Hpyrimid). Mass spectrum, m/z: 567.2936 [M + H]+. C29H38N6O6. [M + H]+ 567.2928.Methyl 7-[2-R-4-methylpyrimidin-5-yl]-1,2,4-triazolo[1,5-a]pyrimidine-6-carboxylate 6a–6e (ge-neral procedure). A mixture of 6 mmol of 3-(2-R-4-methylpyrimidin-5-yl)-3-oxopropionic acid ester 1a–1c and 6 mmol of DMFDMA was heated under refl ux in6 mL of isopropanol for 2 h. After cooling, 5 mmol of the corresponding 5-amino-1,2,4-triazole 3a–3c was added. The precipitate formed after cooling of the reaction mixture was fi ltered off, washed with isopropanol, and recrystallized from isopropanol–DMF.Methyl 7-[4-methyl-2-(piperidin-1yl)pyrimidin-5-yl]-1,2,4-triazolo[1,5-a]pyrimidine-6-carboxylate (6a). Yield 1.20 g (59%), white amorphous material, mp 182–185°C. 1H NMR spectrum (DMSO-d6), δ, ppm: 1.51–1.56 m (6H, CH2CH2CH2), 2.16 s (3H, CH3), 3.65 t (4H, CH2NCH2, J 5.0 Hz), 3.74 s (3H, CH3O), 8.24 s (1H, CHtriaz), 8.73 s (1H, CHpyrimid), 9.31 s (1H, CHpyrimid). Mass spectrum, m/z: 354.1670 [M + H]+. C17H19N7O2. [M + H]+ 354.1674.Methyl 7-[4-methyl-2-(piperidin-1yl)pyrimidin-5-yl]-2-phenyl-1,2,4-triazolo[1,5-a]pyrimidine-6-carboxylate (6b). Yield 1.53 g (69%), white amorphous material, mp 268–270°C. 1H NMR spectrum (DMSO-d6), δ, ppm: 1.51–1.57 m (6H, CH2CH2CH2), 2.16 s (3H, CH3), 3.76 t (4H, CH2NCH2, J 5.0 Hz),3.73 s (3H, CH3O), 7.02 t (1Harom, J 7.4 Hz), 7.31 t (2Harom, J 8.1 Hz), 7.73 d (2Harom, J 8.1 Hz), 8.78 s (1H, CHpyrimid), 9.39 s (1H, CHpyrimid). Mass spectrum, m/z: 430.1995 [M + H]+. C23H23N7O2. [M + H]+ 430.1987.Methyl 7-[4-methyl-2-(morpholin-4-yl)pyrimidin-5-yl]-1,2,4-triazolo[1,5-a]pyrimidine-6-carboxylate (6c). Yield 1.13 g (53%), white amorphous material, mp 268–270°C. 1H NMR spectrum (DMSO-d6), δ, ppm: 2.14 s (3H, CH3), 3.72 t (4H, CH2NCH2, J 5.0 Hz), 3.78 s (3H, CH3O), 3.84 t (4H, CH2OCH2, J 5.0 Hz), 8.24 s (1H, CHtriaz), 8.75 s (1H, CHpyrimid), 8.82 s (1H, CHpyrimid). Mass spectrum, m/z: 356.1466 [M + H]+. C16H17N7O3. [M + H]+ 356.1466.Methyl 7-[4-methyl-2-(morpholin-4-yl)pyrimi-din-5-yl]-2-phenyl-1,2,4-triazolo[1,5-a]pyrimidine-6-carboxylate (6d). Yield 1.53 g (71%), white amorphous material, mp 202–204°C. 1H NMR spectrum (DMSO-d6), δ, ppm: 2.13 s (3H, CH3), 3.75 t (4H, CH2NCH2, J 5.0 Hz), 3.78 s (3H, CH3O), 3.86 t (4H, CH2OCH2, J 5.5 Hz), 7.12 t (1Harom, J 7.4 Hz), 7.40 t (2Harom, J 8.1 Hz), 7.76 d (2Harom, J 8.1 Hz), 8.21 s (1H, CHpyrimid), 8.84 s (1H, CHpyrimid). Mass spectrum, m/z: 432.1788 [M + H]+. C22H21N7O3. [M + H]+ 432.1780.Methyl 7-[4-methyl-2-(pyrrolidin-1-yl)pyrimidin-5-yl]-2-(methylsulfanyl)-1,2,4-triazolo[1,5-a]py-rimidine-6-carboxylate (6e). Yield 1.01 g (44%), white amorphous material, mp 161–163°C. 1H NMR spectrum (DMSO-d6), δ, ppm: 1.53–1.60 m (4H, CH2CH2), 2.15 s(3H, CH3), 2,38 s (3H, CH3S), 3.78 t (4H, CH2NCH2, J 5.8 Hz), 3.77 s (3H, CH3O), 8.76 s (1H, CHpyrimid),8.87 s (1H, CHpyrimid). Mass spectrum, m/z: 386.1388 [M + H]+. C17H19N7O2S. [M + H]+ 386.1395.CONCLUSIONSA convenient synthetic approach to polysubstituted dehydrogenated or heteroaromatic 1,2,4-triazolo[1,5-a]-pyrimidines containing containing at position 5 a 4-methylpyrimidine moiety bearing a cycloamino substituent at position 2 and linked to the triazo-lopyrimidine bicycle through its position 5 was developed. This allows creation of a target library of new hybrid molecules containing in their structure two privileged scaffolds, one of which has an antibacterial and the other an anticoagulant activity.FUNDINGThe study was carried out with a grant from the Russian Science Foundation (project no. 18-74-10097).RUSSIAN  JOURNAL  OF ORGANIC  CHEMISTRY  Vol.  57  No.  2  2021225THREE-COMPONENT CONDENCATIONS OF 3-AMINO-1,2,4-TRIAZOLESCONFLICT OF INTERESTThe authors declare no confl ict of interest.REFERENCES 1. Kumar, H.M.S., Herrmann, L., and Tsogoeva, S.B.,Bioorg. Med. Chem. Lett., 2020, vol. 30, p. 127514.https://doi.org/10.1016/j.bmcl.2020.127514 2. Singh, P.K., Choudhary, S., Kashyap, A., Verma, H., Kapil, S., Kumar, M., Arora, M., and Silakari, O., Bioorg. Chem., 2019, vol. 88, p. 102919. https://doi.org/10.1016/j.bioorg.2019.102919 3. Desantis, J., Massari, S., Corona, A., Astolfi , A., Sabatini, S., Manfroni, G., Palazzotti, D., Cecchetti, V.,Pannecouque, Ch., Tramontano, E., and Tabarrini, O., Molecules, 2020, vol. 25, p. 1183. https://doi.org/10.3390/molecules25051183 4. Berger, Y., Dehmlow, H., Blum-Kaelin, D., Kitas, E.A., Löffl er, B.-M., Aebi, J.D., and Juillerat-Jeanneret, L.,J. Med. Chem., 2005, vol. 48, p. 483. https://doi.org/10.1021/jm040857x 5. Yamaki, S., Koga, Y., Nagashima, A., Kondo, M., Shimada, Y., Kadono, K., Moritomo, A., and Yoshiha-ra, K., Bioorg. Med. Chem., 2017, vol. 25, p. 4110.https://doi.org/10.1016/j.bmc.2017.05.059 6. Kumar, C.V., Kavitake, S., Kumar, S.S., Cornwall, P., Ashok, M., Bhagat, S., Manjunatha, S.G., and Nambiar, S., Org. Process Res. Dev., 2012, vol. 16, p. 1416. https://doi.org/10.1021/op300120r 7. Sakamoto, T., Koga, Y., Hikota, M., Matsuki, K., Murakami, M., Kikkawa, K., Fujishige, K., Kotera, J.,Omori, K., Morimoto, H., and Yamada, K., Bioorg. Med. Chem. Lett., 2014, vol. 24, p. 5460. https://doi.org/10.1016/j.bmcl.2014.10.008 8. Lipson, V.V., Desenko, S.M., Shirobokova, M.G., andBorodina, V.V., Chem. Heterocycl. Compd., 2003, vol. 39,p. 1213. https://doi.org/10.1002/chin.200420157 9. Lipson, V.V., Desenko, S.M., Shishkina, S.V., Shi-robokova, M.G., Shishkin, O.V., and Orlov, V.D., Chem. Heterocycl. Compd., 2003, vol. 39, p. 1041. https://doi.org/10.1023/B:COHC.0000003522.71893.7710. Lipson, V.V., Orlov, V.D., Desenko, S.M., Shishkin, O.V.,Shishkina, S.V., and Shirobokova, M.G., Chem. Heterocycl.Compd., 2000, vol. 36, p. 1039. https://doi.org/10.1023/A:100277771415811. Lipson, V.V., Borodina, V.V., and Shirobokova, M.G., Ukr. Khim. Zh., 2005, vol. 71, p. 95.12. Shaabani, A., Rahmati, A., Farhang, E., and Rezayan, A.H.,Monatsh. Chem., 2007, vol. 138, p. 615. https://doi.org/10.1007/s00706-007-0641-213. Kryl’skii, D.V., Shikhaliev, Kh.S., and Potapov, A.Yu., Izv. Vuzov, Khim. Khim. Tekhnol., 2005, vol. 48, p. 72.14. Shikhaliev, Kh.S., Kryl’skii, D.V., Potapov, A.Yu., and Krysin, M.Yu., Russ. Chem. Bull., 2005, vol. 54, p. 2903.https://doi.org/10.1007/s11172-006-0207-115. Titova, Yu.A., Filatova, E.S., Fedorova, O.V., Rusi-nov, G.L., and Charushin, V.N., Russ. J. Org. Chem., 2019,vol. 55, p. 775. https://doi.org/10.1134/S051474921906006516. Potapov, A.Yu., Falaleev, A.V., Shikhaliev, Kh.S., and Shatalov, G.V., Russ. Chem. Bull., 2014, vol. 63, p. 2198.https://doi.org/10.1007/s11172-014-0720-6

Three-component condencations of 3-amino-1,2,4-triazoles, methyl 3-(2-cycloamino-4-methylpyrimidin-5-yl)-3- oxopropionoates, and a series of c1 synthons as a convenient approach to pyrimidin-5-yl-1,2,4-triazolo[1,5-a] pyrimidines

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Three-component condencations of 3-amino-1,2,4-triazoles, methyl 3-(2-cycloamino-4-methylpyrimidin-5-yl)-3- oxopropionoates, and a series of c1 synthons as a convenient approach to pyrimidin-5-yl-1,2,4-triazolo[1,5-a] pyrimidines

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