Ethyl 7-Methyl-1-(4-nitrophenyl)-5-phenyl-3-(thiophen-2-yl)-1,5-dihydro-[1,2,4]triazolo[4,3-a]pyrimidine-6-carboxylate

Abstract

A novel compound, ethyl 7-methyl-1-(4-nitrophenyl)-5-phenyl-3-(thiophen-2-yl)-1,5-dihydro[1,2,4]triazolo[4,3-a]pyrimidine-6-carboxylate (7) was synthesized by reaction of N-(4-nitrophenyl)thiophene-2-carbohydrazonoyl chloride (1) with ethyl 6-methyl-4-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (2). The mechanism of the studied reaction is discussed and the assigned structure was confirmed by elemental analysis and spectral data. Moreover, the in vitro antitumor activities against human lung (A-549) and human hepatocellular carcinoma (HepG-2) cell lines were determined by the MTT method, and the results indicated a high potency compared with the employed standard antitumor drug (Cisplatin).

Synthesis and Structure of 6-Acetyl-2-Arylhydrazone Derivatives of Thiazolo[3,2-a]Pyrimidine

“…Yield 44%, white powder, mp 165-166 • C. 1 H NMR (400 MHz, CDCl 3 , 25 • C) δH ppm: 0.75 (d, J = 6.9 Hz, 3H, CH(OH)CH 3 ), 1.17 (d, J = 6.0 Hz, 3H, CH 3 ), 1.99-2.05 (m, 1H, CH-6), 3.60-3.65 (m, 1H, CH-N), 4.31-4.36 (m, 1H, CH-OH), 4.39 (d, J = 5.9 Hz, 2H, CH 2 OH), 5.15 (d, J = 4.6 Hz, 1H, CHOH), 5.63 (t, J = 6.0 Hz, 1H, CH 2 OH), 7.01-7.07 (m, 1H, CH (Ph)), 7.12-7.16 (m, 1H, CH (Ph)), 7.21-7.25 (m, 2H, CH (Ph)), 7.43-7.45 (m, 2H, CH (Ph)), 8.17-8.19 (m, 2H, CH (Ph)). 13 C NMR (100 MHz, CDCl 3 , 25 Crystals of 3a suitable for X-ray diffraction study were obtained by slow evaporation of ethanol solution (20 mL) containing 0.02 mol of the dissolved compound after 5 days.…”

“…The crystallographic data of structure 7 were deposited at the Cambridge Crystallographic Data Center, and the registration numbers and the most important characteristics are given in Table 1. The structure of compounds 2a and 3a-c was established by 1 H and 13 C NMR IR-, and mass-spectra (see Figures S1-S15). The structure of derivative 3a was additionally confirmed by SCXRD (Table 1).…”

“…It is interesting to note that the established hydrogen interaction leads to the formation of zigzag heterochiral chains in the crystalline phase (Figure 1c). Heterochiral chains consisting of alternating R-and S- The structure of compounds 2a and 3a-c was established by 1 H and 13 C NMR IR-, and mass-spectra (see Figures S1-S15). The structure of derivative 3a was additionally confirmed by SCXRD (Table 1).…”

“…The signals of the C6 and C7 atoms of triazolo[4,3-a]pyrimidine 4 in the 13 C NMR spectrum shift were upfield and appeared at 47.1 and 48.6 ppm, respectively. In the 1 H NMR spectrum, the signals of hydrogen atoms at C6 and C7 resonated at 1.99-2.05 ppm and 3.60-3.65 ppm as multiplets.…”

Recent Synthetic and Biological Developments on 1,2,4‐Triazolopyrimidines

“…Ethyl‐methyl‐1‐(4‐nitrophenyl)‐5‐phenyl‐3‐(thiophen‐2‐yl)‐1,5‐dihydro‐[1,2,4]triazolo[4,3‐a]pyrimidine‐6‐carboxylate (3) was prepared from N‐(4‐nitrophenyl)thiophene‐2‐carbohydraz‐ onoyl chloride ( 224 ) and ethyl‐6‐methyl‐4‐phenyl‐2‐thioxo‐1,2,3,4‐tetrahydropyrimidine‐5‐carboxylate ( 225 ) (Scheme 43). [103] These starting precursors reacts in presence of catalytic triethylamine with 1,4‐dioxane as a solvent to offered the title product via initial S‐alkylation of 224 followed by smile rearrangement and in situ elimination reactions. The synthesized 1,2,4‐triazolo[4,3‐a]pyrimidine 226 displayed improved potency compared to standard cisplatin drug.…”