Next Article in Journal
1-(8-Chloro-3-methyl-1H-pyrazolo[4,3-c]cinnolin-1-yl)-2-(2-chlorophenyl)ethanone
Previous Article in Journal
3-[1-(4-Methylphenyl)-3-oxo-1,3,4,5,6,7-hexahydro-2H-isoindol-2-yl]propanoic Acid
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Short Note

Ethyl (1,3-diphenyl-1H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-yl)acetate

Department of Chemistry, Faculty of Science, University of Cairo, Giza, 12613, Egypt
*
Author to whom correspondence should be addressed.
Molbank 2011, 2011(4), M743; https://doi.org/10.3390/M743
Submission received: 16 August 2011 / Accepted: 13 October 2011 / Published: 10 November 2011

Abstract

:
Novel ethyl (1,3-diphenyl-1H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-yl)acetate (5), was prepared via heating of 5-amino-1,3-diphenyl-4,5-dihydro-4-imino-1H-pyrazolo[3,4-d] pyrimidine (1) and diethyl malonate (2) under reflux. The structure of the synthesized compound was assigned on the basis of its elemental analysis, IR, 1H-NMR and mass spectral data.

Graphical Abstract

Pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine exhibits interesting pharmacological activities such as glycogen synthase kinase-3 inhibitors [1], xanthine oxidase (XO) inhibitors [1] and adenosine receptor antagonists [2,3,4,5,6,7,8,9,10,11]. These observations led us to synthesize a new pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine from 5-amino-1,3-diphenyl-4,5-dihydro-4-imino-1H-pyrazolo[3,4-d]pyrimidine and diethyl malonate.

Results and Discussion

5-Amino-1,3-diphenyl-4,5-dihydro-4-imino-1H-pyrazolo[3,4-d]pyrimidine (1) [12] was allowed to react with diethyl malonate (2) under reflux. The expected product of this reaction was structure 9,11-diphenylpyrazolo[3',4':4,5]pyrimido[1,6-b][1,2,4]triazepin-2,4-dione (3) or 4-ethoxy-9,11-diphenylpyrazolo[3',4':4,5]pyrimido[1,6-b][1,2,4]triazepin-2-one (4) or its isomeric ethyl (1,3-diphenyl-1H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-yl)acetate (5) (Scheme 1). MS, 1H NMR, IR and elemental analyses data of the isolated product were in full agreement with the structure 5 not the isomeric structures 3 or 4. The IR spectrum of the isolated product showed bands at 1735 cm−1 characteristic for ester carbonyl group. Its 1H NMR spectrum showed a singlet signal at δ 4.12 for the acyclic CH2 protons, in addition to triplet and quartet signals at δ 1.25 and 4.22 due to the protons of ethyl group.
Synthesis of ethyl (1,3-diphenyl-1H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-yl)acetate (5). A mixture of 5-amino-1,3-diphenyl-4-iminopyrazolo[3,4-b]pyrimidine (1) [12] (3.02 g, 10 mmol) and diethyl malonate (2) (2.4 g, 15 mmol) was heated under reflux for 2 h. After cooling, the solid precipitated was collected and crystallized from ethanol/dioxane mixture (1:1).
Yield: 96%; Yellow crystals; m.p. 200–202 °C.
GC-MS m/z (%): 399 (M++ 1, 12), 398 (M+, 50), 326 (43), 256 (4), 127 (8),77 (100), 51 (65).
IR (KBr) vmax cm−1: 1735 (C=O).
1H NMR (300 MHz, CDCl3): δ(ppm) = 1.25 (t, J = 7 Hz, 3H, CH3), 4.12 (s, 2H, CH2), 4.22 (q, J = 7 Hz, 2H, CH2), 7.47-8.70 (m, 10H, Ar-H), 9.69 (s, 1H, pyrimidine-H).
13C NMR (75 MHz, DMSO-d6): 13.99, 34.64, 60.83, 100.62, 122.0, 127.04, 127.31, 128.43, 129.01, 137.73, 138.71, 140.00, 143.83, 145.10, 146.58, 148.14, 161.19, 168.41.
Anal. Calcd. for C22H18N6O2(398.15): C, 66.32; H, 4.55; N, 21.09. Found: C, 66.18; H, 4.42; N, 20.89%.

Supplementary materials

Supplementary File 1Supplementary File 2Supplementary File 3

References and Notes

  1. Nagamatsu, T.; Fujita, T. Facile and general syntheses of 3- and/or 5-substituted 7H-pyrazolo[4,3- e]-1,2,4-triazolo[4,3-c]pyrimidines as a new class of potential xanthine oxidase inhibitors. Chem. Commun. 1999, 1461–1462. [Google Scholar] [CrossRef]
  2. Ongini, E.; Monopoli, A.; Cacciari, B.; Baraldi, P.G. Selective adenosine A2A receptor antagonists. Il Farmaco 2001, 56, 87–90. [Google Scholar] [CrossRef]
  3. Kishore, D.P.; Balakumar, C.; Rao, A.R.; Roy, P.P.; Roy, K. QSAR of adenosine receptor antagonists: Exploring physicochemical requirements for binding of pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine derivatives with human adenosine A3 receptor subtype. Bioorg. Med. Chem. Lett. 2011, 21, 818–823. [Google Scholar] [CrossRef] [PubMed]
  4. Baraldi, P.G.; Manfredini, S.; Simoni, D.; Zappaterra, L.; Zocchi, C.; Dionisotti, S.; Ongini, E. Synthesis of new pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine and 1,2,3-triazolo[4,5-e]1,2,4-triazolo[1,5-c]pyrimidine displaying potent and selective activity as A2a adenosine receptor antagonists. Bioorg. Med. Chem. Lett. 1994, 4, 2539–2544. [Google Scholar] [CrossRef]
  5. Kumar, T.S.; Mishra, S.; Deflorian, F.; Yoo, L.S.; Phan, K.; Kecskés, M.; Szabo, A.; Shinkre, B.; Gao, Z.-G.; Trenkle, W.; Jacobson, K.A. Molecular probes for the A2A adenosine receptor based on a pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine scaffold. Bioorg. Med. Chem. Lett. 2011, 21, 2740–2745. [Google Scholar] [CrossRef] [PubMed]
  6. Dolzhenko, A.V.; Pastorin, G.; Dolzhenko, A.V.; Chui, W.K. A new synthesis of 2,8-disubstituted pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidines. Tetrahedron Lett. 2009, 50, 5617–5621. [Google Scholar] [CrossRef]
  7. Baraldi, P.G.; El-Kashef, H.; Farghaly, A.; Vanelle, P.; Fruttarolo, F. A new synthesis of 2,8-disubstituted pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidines and related heterocycles. Tetrahedron 2004, 60, 5093–5104. [Google Scholar] [CrossRef]
  8. Harris, J.M.; Neustadt, B.R.; Zhang, H.; Lachowicz, J.; Cohen-Williams, M.; Varty, G.; Hao, J.; Stamford, A.W. Potent and selective adenosine A2A receptor antagonists: [1,2,4]Triazolo[4,3-c]pyrimidin-3-ones. Bioorg. Med. Chem. Lett. 2011, 21, 2497–2501. [Google Scholar] [CrossRef] [PubMed]
  9. Baraldi, P.G.; Bovero, A.; Fruttarolo, F.; Romagnoli, R.; Tabrizi, M.A.; Preti, D.; Varani, K.; Borea, P.A.; Moorman, A.R. New strategies for the synthesis of A3 adenosine receptor antagonists. Bioorg. Med. Chem. 2003, 11, 4161–4169. [Google Scholar] [CrossRef]
  10. Michielan, L.; Bolcato, C.; Federico, S.; Cacciari, B.; Bacilieri, M.; Klotz, K.-N.; Kachler, S.; Pastorin, G.; Cardin, R.; Sperduti, A.; Spalluto, G.; Moro, S. Combining selectivity and affinity predictions using an integrated Support Vector Machine (SVM) approach: An alternative tool to discriminate between the human adenosine A2A and A3 receptor pyrazolo-triazolo-pyrimidine antagonists binding sites. Bioorg. Med. Chem. 2009, 17, 5259–5274. [Google Scholar] [CrossRef] [PubMed]
  11. Paeshuyse, J.; Letellier, C.; Froeyen, M.; Dutartre, H.; Vrancken, R.; Canard, B.; De Clercq, E.; Gueiffier, A.; Teulade, J.-C.; Herdewijn, P.; Puerstinger, G.; Koenen, F.; Kerkhofs, P.; Baraldi, P.G.; Neyts, J. A pyrazolotriazolopyrimidinamine inhibitor of bovine viral diarrhea virus replication that targets the viral RNA-dependent RNA polymerase. Antiviral Res. 2009, 82, 141–147. [Google Scholar] [CrossRef] [PubMed]
  12. Shawali, A.S.; Fahmi, A.A.; Albar, H.A.; Hassaneen, H.M.; Abdelhamid, H.A. A facile synthesis of some pyrazolo analogues of tricyclic purine derivatives via hydrazonoyl halides. J. Chem. Res. (S) 1994, 6, 1040–1049. [Google Scholar]
Scheme 1. Synthesis of the title compound (5).
Scheme 1. Synthesis of the title compound (5).
Molbank 2011 m743 sch001

Share and Cite

MDPI and ACS Style

Farghaly, T.A.; Gomha, S.M. Ethyl (1,3-diphenyl-1H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-yl)acetate. Molbank 2011, 2011, M743. https://doi.org/10.3390/M743

AMA Style

Farghaly TA, Gomha SM. Ethyl (1,3-diphenyl-1H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-yl)acetate. Molbank. 2011; 2011(4):M743. https://doi.org/10.3390/M743

Chicago/Turabian Style

Farghaly, Thoraya A., and Sobhi M. Gomha. 2011. "Ethyl (1,3-diphenyl-1H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-yl)acetate" Molbank 2011, no. 4: M743. https://doi.org/10.3390/M743

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop