Skip to main content
SpringerLink
Log in

Facile Regioselective On-Water Synthesis of 4,7-Dihydropyrazolo[1,5-a]Pyrimidines and 4,7-Dihydro[1,2,4]Triazolo[1,5-a]Pyrimidines

  • Published:
Chemistry of Heterocyclic Compounds Aims and scope

Efficient and regioselective on-water synthesis of variously substituted 5-amino-4,7-dihydropyrazolo[1,5-a]pyrimidine-6-carbonitriles and 5-amino-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-6-carbonitriles using 1,8-diazabicyclo[5.4.0]undec-7-ene as catalyst has been demonstrated. The reaction of 2-benzylidenemalononitriles and 3-aryl-1H-pyrazol-5-amines or 1H-1,2,4-triazol-5-amine allows to obtain the respective pyrazolo[1,5-a]pyrimidines and [1,2,4]triazolo[1,5-a]pyrimidines in high yields up to 93%. Main advantages of the developed synthetic protocol are application of water as environmentally friendly solvent, short reaction times, simple workup procedure that often does not require further purification of products, and broad substrate scope.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1.

Similar content being viewed by others

References

  1. (a) Quin, L. D.; Tyrell, J. A. Fundamentals of Heterocyclic Chemistry: Importance in Nature and in the Synthesis of Pharmaceuticals; John Wiley & Sons: Hoboken, 2010. (b) Vitaku, E.; Smith, D. T.; Njardarson, J. T. J. Med. Chem. 2014, 57, 10257. (c) Joule, J. A.; Mills, K. Heterocyclic Chemistry; Wiley-Blackwell: Chichester, 2010, 5th ed.

  2. Hougaard, C.; Hammami, S.; Eriksen, B. L.; Sørensen, U. S.; Jensen, M. L.; Strøbæk, D.; Christophersen, P. Mol. Pharmacol. 2012, 81, 210.

    Article  CAS  PubMed  Google Scholar 

  3. Gomez, L.; Massari, M. E.; Vickers, T.; Freestone, G.; Vernier, W.; Ly, K.; Xu, R.; McCarrick, M.; Marrone, T.; Metz, M.; Yan, Y. G.; Yoder, Z. W.; Lemus, R.; Broadbent, N. J.; Barido, R.; Warren, N.; Schmelzer, K.; Neul, D.; Lee, D.; Andersen, C. B.; Sebring, K.; Aertgeerts, K.; Zhou, X.; Tabatabaei, A.; Peters, M.; Breitenbucher, J. G. J. Med. Chem. 2017, 60, 2037.

    Article  CAS  PubMed  Google Scholar 

  4. Wang, S.; Zhao, L.-J.; Zheng, Y.-C.; Shen, D.-D.; Miao, E.-F.; Qiao, X.-P.; Zhao, L.-J.; Liu, Y.; Huang, R.; Yu, B.; Liu, H.-M. Eur. J. Med. Chem. 2017, 125, 940.

    Article  CAS  PubMed  Google Scholar 

  5. da Silva, E. R.; Boechat, N.; Pinheiro, L. C. S.; Bastos, M. M.; Costa, C. C. P.; Bartholomeu, J. C.; da Costa, T. H. Chem. Biol. Drug Des. 2015, 86, 969.

    Article  CAS  PubMed  Google Scholar 

  6. Faizi, M.; Dabirian, S.; Tajali, H.; Ahmadi, F.; Zavareh, E. R.; Shahhosseini, S.; Tabatabai, S. A. Bioorg. Med. Chem. 2015, 23, 480.

    Article  CAS  PubMed  Google Scholar 

  7. Arenas-González, A.; Mendez-Delgado, L. A.; Merino-Montiel, P.; Padrón, J. M.; Montiel-Smith, S.; Vega-Báez, J. L.; Meza-Reyes, S. Steroids 2016, 116, 13.

    Article  CAS  PubMed  Google Scholar 

  8. (a) Kokkonda, S.; Deng, X.; White, K. L.; Coteron, J. M.; Marco, M.; de las Heras, L.; White, J.; El Mazouni, F.; Tomchick, D. R.; Manjalanagara, K.; Rudra, K. R.; Chen, G.; Morizzi, J.; Ryan, E.; Kaminsky, W.; Leroy, D.; Santos Martínez-Martínez, M.; Jimenez-Diaz, M. B.; Ferrer Bazaga, S.; Angulo-Barturen, I.; Waterson, D.; Burrows, J. N.; Matthews, D.; Charman, S. A.; Phillips, M. A.; Rathod, P. K. J. Med. Chem. 2016, 59, 5416. (b) Phillips, M. A.; White, K. L.; Kokkonda, S.; Deng, X.; White, J.; El Mazouni, F.; Marsh, K.; Tomchick, D. R.; Manjalanagara, K.; Rudra, K. R.; Wirjanata, G.; Noviyanti, R.; Price, R. N.; Marfurt, J.; Shackleford, D. M.; Chiu, F. C. K.; Campbell, M.; Jimenez-Diaz, M. B.; Ferrer Bazaga, S.; Angulo-Barturen, I.; Santos Martinez, M.; Lafuente-Monasterio, M.; Kaminsky, W.; Silue, K.; Zeeman, A.-M.; Kocken, C.; Leroy, D.; Blasco, B.; Rossignol, E.; Rueckle, T.; Matthews, D.; Burrows, J. N.; Waterson, D.; Palmer, M. J.; Rathod, P. K.; Charman, S. A. ACS Infect. Dis. 2016, 2, 945.

  9. (a) Flynn, J.; Jones, J.; Johnson, A. J.; Andritsos, L.; Maddocks, K.; Jaglowski, S.; Hessler, J.; Grever, M. R.; Im, E.; Zhou, H.; Zhu, Y.; Zhang, D.; Small, K.; Bannerji, R.; Byrd, J. C. Leukemia 2015, 29, 1524 (b) Criscitiello, C.; Viale, G.; Esposito, A.; Curigliano, G. Expert Opin. Invest. Drugs 2014, 23, 13..

  10. (a) Yu, P. B.; Hong, C. C.; Sachidanandan, C.; Babitt, J. L.; Deng, D. Y.; Hoyng, S. A.; Lin, H. Y.; Bloch, K. D.; Peterson, R. T. Nat. Chem. Biol. 2008, 4, 33. (b) Yamamoto, Y.; Sawa, R.; Wake, I.; Morimoto, A.; Okimura, Y. Nutr. Res. 2017, 47, 13.

  11. (a) Yano, W.; Inoue, N.; Ito, S.; Itou, T.; Yasumura, M.; Yoshinaka, Y.; Hagita, S.; Goto, M.; Nakagawa, T.; Inoue, K.; Tanabe, S.; Kaku, K. J. Diabetes Investig. 2017, 8, 155. (b) Ikedo, T.; Minami, M.; Kataoka, H.; Hayashi, K.; Nagata, M.; Fujikawa, R.; Higuchi, S.; Yasui, M.; Aoki, T.; Fukuda, M.; Yokode, M.; Miyamoto, S. J. Am. Heart Assoc. 2017, 6, e004777. (c) Kato, N.; Oka, M.; Murase, T.; Yoshida, M.; Sakairi, M.; Yamashita, S.; Yasuda, Y.; Yoshikawa, A.; Hayashi, Y.; Makino, M.; Takeda, M.; Mirensha, Y.; akigami, T. Bioorg. Med. Chem. 2011, 19, 7221.

  12. (a) El-Gendy, M. M. A.; Shaaban, M.; Shaaban, K. A.; l-Bondkly, A. M.; Laatsch, H. J. Antibiot. 2008, 61, 149. (b) Wang, H.; Hesek, D.; Lee, M.; Lastochkin, E.; Oliver, A. G.; Chang, M.; Mobashery, S. J. Nat. Prod. 2016, 79, 1219.

  13. Ohnishi, H.; Yamaguchi, K.; Shimada, S.; Suzuki, Y.; Kumagai, A. Life Sci. 1981, 28, 1641.

    Article  CAS  PubMed  Google Scholar 

  14. (a) Rodríguez-Torres, M.; Yoshida, E. M.; Marcellin, P.; Srinivasan, S.; Purohit, V. S.; Wang, C.; Hammond, J. L. Ann. Hepatol. 2014, 13, 364. (b) Successful Strategies for the Discovery of Antiviral Drugs; Desai, M. C.; Meanwell, N. A., Eds.; The Royal Society of Chemistry: Cambridge, 2013.

  15. Youssef, Y. A.; Kamel, M. M.; Taher, M. S.; Ali, N. F.; Abd El Megiede, S. A. J. Saudi Chem. Soc. 2014, 18, 220.

    Article  CAS  Google Scholar 

  16. (a) Dandia, A.; Khan, S.; Sharma, R.; Parihar, S.; Parewa, V. ChemistrySelect 2017, 2, 9684. (b) Butler, R. N.; Coyne, A. G. Org. Biomol. Chem. 2016, 14, 9945.

  17. (a) Cherukupalli, S.; Karpoormath, R.; Chandrasekaran, B.; Hampannavar, G. A.; Thapliyal, N.; Palakollu, V. N. Eur. J. Med. Chem. 2017, 126, 298. (b) Fizer, M.; Slivka, M. Chem. Heterocycl. Compd. 2016, 52, 155. [Khim. Geterotsikl. Soedin. 2016, 52, 155.]

  18. (a) Sakhno, Y. I.; Kozyryev, A. V; Desenko, S. M.; Shishkina, S. V; Musatov, V. I.; Sysoiev, D. O.; Chebanov, V. A. Tetrahedron 2018, 74, 564. (b) Kumar, P. M.; Kumar, K. S.; Mohakhud, P. K.; Mukkanti, K.; Kapavarapu, R.; Parsa, K. V. L.; Pal, M. Chem. Commun. 2012, 48, 431. (c) Soares de Melo, C.; Feng, T.-S.; van der Westhuyzen, R.; Gessner, R. K.; Street, L. J.; Morgans, G. L.; Warner, D. F.; Moosa, A.; Naran, K.; Lawrence, N.; Boshoff, H. I. M.; Barry III, C. E.; Harris, C. J.; Gordon, R.; Chibale, K. Bioorg. Med. Chem. 2015, 23, 7240. (d) Mokhtar, M.; Saleh, T. S.; Basahel, S. N. J. Mol. Catal. A: Chem. 2012, 353–354, 122. (e) Bartels, B.; Bolas, C. G.; Cueni, P.; Fantasia, S.; Gaeng, N.; Trita, A. S. J. Org. Chem. 2015, 80, 1249. (f) Kaping, S.; Kalita, U.; Sunn, M.; Singha, L. I.; Vishwakarma, J. N. Monatsh. Chem. 2016, 147, 1257. (g) Shekarrao, K.; Kaishap, P. P.; Saddanapu, V.; Addlagatta, A.; Gogoi, S.; Boruah, R. C. RSC Adv. 2014, 4, 24001. (h) Castillo, J.-C.; Rosero, H.-A.; Portilla, J. RSC Adv. 2017, 7, 28483. (i) Farahi, M.; Karami, B.; Banaki, Z. Chin. Chem. Lett. 2015, 26, 1065. (j) Scapin, E.; Salbego, P. R. S.; Bender, C. R.; Meyer, A. R.; Pagliari, A. B.; Orlando, T.; Zimmer, G. C.; Frizzo, C. P.; Bonacorso, H. G.; Zanatta, N.; Martins, M. A. P. Beilstein J. Org. Chem. 2017, 13, 2396. (k) Bharath, Y.; Rao, M. V. B.; Pal, M. Lett. Drug Des. Discovery 2017, 14, 1206. (l) Aggarwal, R.; Kumar, S. Beilstein J. Org. Chem. 2018, 14, 203. (m) Bhatt, J. D.; Chudasama, C. J.; Patel, K. D. Bioorg. Med. Chem. 2015, 23, 7711.

  19. Lancaster, M. Green Chemistry; The Royal Society of Chemistry: Cambridge, 2016, 3rd ed., p. 165.

  20. (a) Anwar, H. F.; Fleita, D. H.; Kolshorn, H.; Meier, H.; Elnagdi, M. H. ARKIVOC 2006, (xv), 133. (b) Al-Matar, H. M.; Khalil, K. D.; Adam, A. Y.; Elnagdi, M. H. Molecules 2010, 15, 6619.

  21. Rahmati, A. C. R. Chim. 2012, 15, 647.

    Article  CAS  Google Scholar 

  22. (a) Hassan, A. S.; Mady, M. F.; Awad, H. M.; Hafez, T. S. Chin. Chem. Lett. 2017, 28, 388. (b) Hassan, A. S.; Hafez, T. S.; Osman, S. A. Sci. Pharm. 2015, 83, 27.

  23. (a) Severina, G. I.; Perehoda, L. A.; Georgiyantc, V. A. Pharm. Rev. 2009, 3, 6 [In Ukrainian]. (b) Attaby, F. A.; Eldin, S. M. Arch. Pharm. Res. 1997, 20, 330.

  24. Khurana, J. M.; Nand, B.; Saluja, P. Tetrahedron 2010, 66, 5637.

    Article  CAS  Google Scholar 

Download references

ACKNOWLEDGEMENT

The authors gratefully acknowledge Mr. Amamudin Ansari for spectroscopic analysis of all synthesized compounds. The authors are thankful to Dr. Jandeep Singh (Assistant Professor, Lovely Professional University, Punjab) for providing help with linguistic corrections.

Author information

Authors and Affiliations

  1. Department of Chemistry, Smt. S. M. Panchal Science College, Talod, Gujarat, 383215, India

    Ravindra M. Gol & Vijaykumar M. Barot

  2. Department of Chemistry, Government Science College, Chikhli, Gujarat, 396521, India

    Taslimahemad T. Khatri

Authors
  1. Ravindra M. Gol
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Taslimahemad T. Khatri
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vijaykumar M. Barot
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Taslimahemad T. Khatri.

Additional information

Supplementary information file, containing IR (compounds 3c, 6b,e, and 7c), 1H and 13C NMR (compounds 3c, 7c,f) spectroscopic and mass spectral data (compounds 3c, 7d), and results of optimization of reaction conditions, is available at the journal website at http://link.springer.com/journal/10593.

Published in Khimiya Geterotsiklicheskikh Soedinenii, 2019, 55(3), 246–253

Electronic supplementary material

ESM 1

(PDF 890 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gol, R.M., Khatri, T.T. & Barot, V.M. Facile Regioselective On-Water Synthesis of 4,7-Dihydropyrazolo[1,5-a]Pyrimidines and 4,7-Dihydro[1,2,4]Triazolo[1,5-a]Pyrimidines. Chem Heterocycl Comp 55, 246–253 (2019). https://doi.org/10.1007/s10593-019-02449-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10593-019-02449-x

Keywords

Search

Navigation