Next Article in Journal
5,11,17,23-Tetra-tert-butyl-25-(2’-pyridylmethylamidocarbonylmethyl)-calix[4]arene
Previous Article in Journal
Ethyl 4,4''-Difluoro-5'-hydroxy-1,1':3',1''-terphenyl-4'-carboxylate
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Molbank
Volume 2011
Issue 4
10.3390/M746
molbank-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Short Note

(E)-Ethyl 3-(Dimethylamino)-2-(7,9-diphenyl-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-2-yl)acrylate

by
Sobhi M. Gomha
and
Thoraya A. Farghaly
*
Department of Chemistry, Faculty of Science, University of Cairo, Giza, 12613, Egypt
*
Author to whom correspondence should be addressed.
Molbank 2011, 2011(4), M746; https://doi.org/10.3390/M746
Submission received: 30 November 2011 / Accepted: 13 December 2011 / Published: 20 December 2011
Browse Figures
Versions Notes

Abstract

:
Novel (E)-ethyl 3-(dimethylamino)-2-(7,9-diphenyl-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-2-yl)acrylate (3A), was prepared via condensation of ethyl (1,3-diphenyl-1H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-yl)acetate (1) and dimethylformamide-dimethylacetal under reflux. The structure of the synthesized compound was assigned on the basis of elemental analysis, IR, 1H NMR and mass spectral data.

Graphical Abstract

Enaminones are poly-dentate reagents that have been utilized extensively in this decade as building blocks in organic synthesis [1,2,3,4,5]. Many reports indicated that the presence of a basic side chain like the N,N-dialkylaminoalkyl group enhances the drugs’ DNA affinity [6] and their anticancer activity, e.g., against the human breast cancer cell line, MCF-7 [7]. In addition, pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidines have been used as potent and selective adenosine A2A receptor antagonists [8,9,10,11,12,13,14,15]. This finding prompted us to condense ethyl (1,3-diphenyl-1H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyri­midin-5-yl)acetate (1) [16] with dimethylformamide-dimethylacetal (DMF-DMA) to obtain the title compound 3A (Scheme 1). Elemental analyses and spectral data were in complete accordance with the assigned structure 3. For example, the 1H NMR spectrum of compound 3 revealed two singlet signals at δ 3.30 and 7.77 ppm characteristic for N,N-dimethylamino and the exocyclic C=CH protons, respectively [1]. The value of the exocyclic C=CH proton signal at δ 7.77 ppm correlated with the E-isomer (3A), while the Z-isomer 3B of an analogous structure was reported to appear at δ 6.9 ppm [17]. Thus, we have successfully synthesized a new enaminone in good yield which can be used as a building blocks for heterocyclic ring systems in organic synthesis.
Synthesis of (E)-ethyl 3-(dimethylamino)-2-(7,9-diphenyl-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-2-yl)acrylate (3)
A mixture of 1 (4.3 g, 10 mmol) and dimethylformamide-dimethylacetal (10 mL) was refluxed for 20 min. After cooling, the precipitate was collected by filtration, washed with methanol and crystallized from dioxane.
Yield: 92%; pale yellow crystals; m.p. 240 °C.
GC-MS m/z (%): 454 (M++ 1, 4), 453 (M+, 13), 380 (11), 336 (12), 167 (23),77 (100), 51 (48).
IR (KBr) vmax cm−1: 1624 (C=O).
1H NMR (Bruker, 300 MHz, CDCl3): δ (ppm) = 1.13 (t, J = 7.0 Hz, 3H, CH3), 3.30 (s, 6H, 2 CH3), 4.07 (q, J = 7.0 Hz, 2H, CH2), 7.47-8.7 (m, 10H, Ar-H), 7.77 (s, 1H, =CH), 9.68 (s, 1H, pyrimidine-H).
Anal. Calcd. for C25H23N7O2 (453.19): C, 66.21; H, 5.11; N, 21.62. Found: C, 66.11; H, 5.01; N, 21.39%.

Supplementary materials

Supplementary File 1Supplementary File 2Supplementary File 3

References

  1. Farghaly, T.A.; Abdel Hafez, N.A.; Ragab, E.A.; Awad, H.M.; Abdalla, M.M. Synthesis, anti-HCV, antioxidant, and peroxynitrite inhibitory activity of fused benzosuberone derivatives. Eur. J. Med. Chem. 2010, 45, 492–500. [Google Scholar] [CrossRef] [PubMed]
  2. Shawali, A.S.; Farghaly, T.A.; Al-Dahshoury, A.R. Synthesis, reactions and antitumor activity of new β-aminovinyl 3- pyrazolyl ketones. ARKIVOC 2009, xiv, 88–89. [Google Scholar]
  3. Farghaly, T.A.; Abdalla, M.M. Synthesis, tautomerism, and antimicrobial, anti-HCV, anti-SSPE, antioxidant, and antitumor activities of arylazobenzosuberones. Bioorg. Med. Chem. 2009, 17, 8012–8019. [Google Scholar] [CrossRef] [PubMed]
  4. Farghaly, T.A.; Riyadh, S.M. Microwave assisted synthesis of annelated benzosuberone as new penta-heterocyclic ring systems. ARKIVOC 2009, x, 54–63. [Google Scholar]
  5. Riyadh, S.M.; Farghaly, T.A.; Abdallah, M.A.; Abdalla, M.M.; Abd El-Aziz, M.R. New pyrazoles incorporating pyrazolylpyrazole moiety: Synthesis, anti-HCV and antitumor activity. Eur. J. Med. Chem. 2010, 45, 1042–1050. [Google Scholar] [CrossRef] [PubMed]
  6. Ducrocq, C.; Wendling, F.; Tourbez-Perrin, M.; Rivalle, C.; Tambourin, P.; Pochon, F.; Bisagni, E.; Chermann, J.C. Structure-activity relationship in a series of newly synthesized 1-amino-substituted ellipticine derivatives. J. Med. Chem. 1980, 23, 1212. [Google Scholar] [CrossRef] [PubMed]
  7. Ahmed, M.S.M.; Farghaly, T.A. Synthesis and reactions of 3-hydrazino-2,7,8,9-tetrahydro-1H-benzo[6′,7′]cyclohepta[1′,2′:4,5]pyrido[2,3-d]pyrimidin-1-one. ARKIVOC 2009, xiii, 31–41. [Google Scholar]
  8. Ongini, E.; Monopoli, A.; Cacciari, B.; Baraldi, P.G. Selective adenosine A2A receptor antagonists. Il Farmaco 2001, 56, 87–90. [Google Scholar] [CrossRef]
  9. 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. Let. 2011, 21, 818–823. [Google Scholar] [CrossRef] [PubMed]
  10. 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]
  11. 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]
  12. 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]
  13. 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]
  14. 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]
  15. 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. Antivir. Res. 2009, 82, 141–147. [Google Scholar] [CrossRef] [PubMed]
  16. Farghaly, T.A.; Gomha, S.M. Synthesis of ethyl (1,3-diphenyl-1H-pyrazolo[4,3-e][1,2,4] triazolo­[1,5-c]pyrimidin-5-yl)acetate. Molbank 2011, 2011, M743. [Google Scholar] [CrossRef]
  17. Bennett, P.; Donnelly, J.A.; Meaney, D.C.; Boyle, P.O. Stereochemistry of cyclopropyl ketones from the reaction of dimethylsulphoxonium methylide with 3-benzylidenechroman-4-ones. J. Chem. Soc. Perkin Trans. 1 1972, 1554. [Google Scholar] [CrossRef]
Molbank 2011 m746 sch001 550
Scheme 1. Synthesis of the title compound (3A).
Scheme 1. Synthesis of the title compound (3A).
Molbank 2011 m746 sch001

Share and Cite

MDPI and ACS Style

Gomha, S.M.; Farghaly, T.A. (E)-Ethyl 3-(Dimethylamino)-2-(7,9-diphenyl-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-2-yl)acrylate. Molbank 2011, 2011, M746. https://doi.org/10.3390/M746

AMA Style

Gomha SM, Farghaly TA. (E)-Ethyl 3-(Dimethylamino)-2-(7,9-diphenyl-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-2-yl)acrylate. Molbank. 2011; 2011(4):M746. https://doi.org/10.3390/M746

Chicago/Turabian Style

Gomha, Sobhi M., and Thoraya A. Farghaly. 2011. "(E)-Ethyl 3-(Dimethylamino)-2-(7,9-diphenyl-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-2-yl)acrylate" Molbank 2011, no. 4: M746. https://doi.org/10.3390/M746

APA Style

Gomha, S. M., & Farghaly, T. A. (2011). (E)-Ethyl 3-(Dimethylamino)-2-(7,9-diphenyl-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-2-yl)acrylate. Molbank, 2011(4), M746. https://doi.org/10.3390/M746

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