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A four-component Biginelli reaction: new opportunities for the synthesis of functionalized pyrimidines

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Chemistry of Heterocyclic Compounds Aims and scope

Methyl 5-aroyl-6-aryl-4-methoxy-2-oxo(thioxo)hexahydropyrimidine-4-carboxylates were synthesized by four-component Biginelli reaction of methyl aroylpyruvate, aromatic aldehyde, urea (thiourea), and MeOH in the presence of NaHSO4. The products were obtained in moderate to high yields.

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References

  1. (a) Biginelli, P. Gazz. Chim. Ital.1893, 23, 360. (b) Kappe, C. O. Tetrahedron1993, 49, 6937. (c) Wan, J.-P.; Liu, Y. Synthesis2010, 3943.

  2. (a) Kappe, C. O. Eur. J. Med. Chem.2000, 35, 1043. (b) Nagarajaiah, H.; Mukhopadhyay, A.; Moorthy, J. N. Tetrahedron Lett. 2016, 57, 5135.

  3. (a) Gartner, M.; Sunder-Plassmann, N.; Seiler, J.; Utz, M.; Vernos, I.; Surrey, T.; Giannis, A. ChemBioChem2005, 6, 1173. (b) Russowsky, D.; Canto, R. F. S.; Sanches, S. A. A.; D'Oca, M. G. M.; de Fátima, Â.; Pilli, R. A.; Kohn, L. K.; Antônio, M. A.; de Carvalho, J. E. Bioorg. Chem. 2006, 34, 173. (c) Tawfik, H. A.; Bassyouni, F.; Gamal-Eldeen, A. M.; Abo-Zeid, M. A.; El-Hamouly, W. S. Pharmacol. Rep. 2009, 61, 1153. (d) Haggarty, S. J.; Mayer, T. U.; Miyamoto, D. T.; Fathi, R.; King, R. W.; Mitchison, T. J.; Schreiber, S. L. Chem. Biol. 2000, 7, 275. (e) Fewell, S. W.; Smith, C. M.; Lyon, M. A.; Dumitrescu, T. P.; Wipf, P.; Day, B. W.; Brodsky, J. L. J. Biol. Chem. 2004, 279, 51131. (f) Karkola, S.; Lilienkampf, A.; Wähälä, K. ChemMedChem2008, 3, 461.

  4. Bhatewara, A.; Jetti, S. R.; Kadre, T.; Paliwal, P.; Jain, S. Int. J. Med. Chem.2013. https://doi.org/10.1155/2013/197612.

  5. Yadlapalli, R. K.; Chourasia, O. P.; Vemuri, K.; Sritharan, M.; Perali, R. S. Bioorg. Med. Chem. Lett.2012, 22, 2708.

    Article  CAS  Google Scholar 

  6. (a) Gein, V. L.; Kholkin, I. V.; Zamaraeva, T. M.; Voronina, E. V.; Vakhrin, M. I. Pharm. Chem. J.2012, 46, 114. [Khim.-Farm. Zh.2012, 46(2), 49.] (b) Gein, V. L.; Fedotov, A. Yu.; Zamaraeva, T. M.; Bobyleva, A. A.; Kasimova, N. N.; Odegova, T. F. Pharm. Chem. J.2013, 46, 720. [Khim.-Farm. Zh.2012, 46(12), 24.] (c) Zamaraeva, T. M.; Odegova, T. F.; Fedotov, A. Yu.; Tomilov, M. V.; Gein, V. L.; Slepukhin, P. A. Russ. J. Gen. Chem.2010, 84, 1950. [Zh. Obshch. Khim.2010, 84, 1672.] (d) Godhani, D. R.; Dobariya, P. B.; Jogel, A. A.; Sanghani, A. M.; Mehta, J. P. Med. Chem. Res.2014, 23, 2417. b Fedorova, O. V.; Filatova, E. S.; Titova, Yu. A.; Kravchenko, M. A.; Medvinskiy, I. D.; Rusinov, G. L.; Charushin, V. N. Russ. Chem. Bull., Int. Ed.2018, 67, 743. [Izv. Akad Nauk, Ser. Khim.2018, 743.]

  7. (a) Kushnir, O. V.; Voloshchuk, O. N.; Eften’eva, R. I.; Marchenko, M. M.; Vovk, M. V. Pharm. Chem. J.2014, 48, 246. [Khim.-Farm. Zh.2014, 48(4), 25.] (b) Zamanova, A. V.; Kurbanova, M. M.; Rzaeva, I. A.; Farzaliev, V. M.; Allakhverdiev, M. A. Russ. J. Appl. Chem.2010, 83, 293. [Zh. Prikl. Khim.2010, 83, 294.]

  8. Ashok, M.; Holla, B. S.; Kumari, N. S. Eur. J. Med. Chem. 2007, 42, 380.

    Article  CAS  Google Scholar 

  9. Atwal, K. S.; Swanson, B. N.; Unger, S. E.; Floyd, D. M.; Moreland, S.; Hedberg, A.; O’Reilly, B. C. J. Med. Chem.1991, 34, 806.

    Article  CAS  Google Scholar 

  10. Marvaniya, H. M.; Parikh, P. K.; Sen, D. J.. J. Appl. Pharm. Sci.2011, 1(5), 109.

    Google Scholar 

  11. Cho, H.; Ueda, M.; Shima, K.; Mizuno, A.; Hayashimatsu, M.; Ohnaka, Y.; Takeuchi, Y.; Hamaguchi, M.; Aisaka, K.; Hidaka, T.; Kawai, M.; Takeda, M.; Ishihara, T.; Funahashi, K.; Satoh, F.; Morita, M.; Noguchi, T. J. Med. Chem.1989, 32, 2399.

    Article  CAS  Google Scholar 

  12. (a) Atwal, K. S.; Rovnyak, G. C.; Kimball, S. D.; Floyd, D. M.; Moreland, S.; Swanson, B. N.; Gougoutas, J. Z.; Schwartz, J.; Smillie, K. M.; Malley, M. F. J. Med. Chem.1990, 33, 2629. (b) Atwal, K. S.; Swanson, B. N.; Unger, S. E.; Floyd, D. M.; Moreland, S.; Hedberg, A.; O’Reilly, B. C. J. Med. Chem.1991, 34, 806.

  13. October, N.; Watermeyer, N. D.; Yardley, V.; Egan, T. J.; Ncokazi, K.; Chibale, K. ChemMedChem2008, 3, 1649.

    Article  CAS  Google Scholar 

  14. Chikhale, R. V.; Bhole, R. P.; Khedekar, P. B.; Bhusari, K. P. Eur. J. Med. Chem.2009, 44, 3645.

    Article  CAS  Google Scholar 

  15. (a) Nagarathnam, D.; Miao, S. W.; Lagu, B.; Chiu, G.; Fang, J.; Murali Dhar, T. G.; Zhang, J.; Tyagarajan, S.; Marzabadi, M. R.; Zhang, F.; Wong, W. C.; Sun, W.; Tian, D.; Wetzel, J. M.; Forray, C.; Chang, R. S. L.; Broten, T. P.; Ransom, R.; Schorn, T. W.; Chen, T. B.; O’Malley, S.; Kling, P.; Schneck, K.; Bendesky, R.; Harrell, C. M.; Vyas, K. P.; Gluchowski, C. J. Med. Chem.1999, 42, 4764. (b) Murali Dhar, T. G.; Nagarathnam, D.; Marzabadi, M. R.; Lagu, B.; Wong, W. C.; Chiu, G.; Tyagarajan, S.; Miao, S. W.; Zhang, F.; Sun, W.; Tian, D.; Shen, Q.; Zhang, J.; Wetzel, J. M.; Forray, C.; Chang, R. S. L.; Broten, T. P.; Schorn, T. W.; Chen, T. B.; O’Malley, S.; Ransom, R.; Schneck, K.; Bendesky, R.; Harrell, C. M.; Vyas, K. P.; Zhang, K.; Gilbert, J.; Pettibone, D. J.; Patane, M. A.; Bock, M. G.; Freidinger, R. M.; Gluchowski, C. J. Med. Chem.1999, 42, 4778. (c) Lagu, B.; Tian, D.; Nagarathnam, D.; Marzabadi, M. R.; Wong, W. C.; Miao, S. W.; Zhang, F.; Sun, W.; Chiu, G.; Fang, J.; Forray, C.; Chang, R. S. L.; Ransom, R. W.; Chen, T. B.; O’Malley, S.; Zhang, K.; Vyas, K. P.; Gluchowski, C. J. Med. Chem.1999, 42, 4794. (d) Wong, W. C.; Sun, W.; Lagu, B.; Tian, D.; Marzabadi, M. R.; Zhang, F.; Nagarathnam, D.; Miao, S. W.; Wetzel, J. M.; Peng, J.; Forray, C.; Chang, R. S. L.; Chen, T. B.; Ransom, R.; O’Malley, S.; Broten, T. P.; Kling, P.; Vyas, K. P.; Zhang, K.; Gluchowski, C. J. Med. Chem.1999, 42, 4804.

  16. Lopez, R.; Rousseau, B.; Kozielsky, F.; Skoufias, D.; De Bonis, S. WO Patent 2006097617.

  17. (a) Ryabukhin, S. V.; Plaskon, A. S.; Bondarenko, S. S.; Ostapchuk, E. N.; Grygorenko, O. O.; Shishkin, O. V.; Tolmachev, A. A. Tetrahedron Lett.2010, 51, 4229. (b) Gein, V. L.; Krylova, I. V.; Tsypliakova, E. P.; Gaifullina, A. R.; Varkentin, L. I.; Vakhrin, M. I. Chem. Heterocycl. Compd. 2009, 45, 829. [Khim. Geterotsikl. Soedin. 2009, 1046.]

  18. (a) Mamedov, V. A.; Mustakimova, L. V.; Gubaidullin, A. T.; Vdovina, S. V.; Litvinov, I. A.; Reznik, V. S. Chem. Heterocycl. Compd.2006, 42, 1229. [Khim. Geterotsikl. Soedin. 2006, 1414.] (b) Saloutin, V. I.; Burgart, Ya. V.; Kuzueva, O. G.; Kappe, C. O.; Chupakhin, O. N. J. Fluorine Chem. 2000, 103, 17. (c). Martins, M. A. P.; Teixeira, M. V. M.; Cunico, W.; Scapin, E.; Mayer, R.; Pereira, C. M. P.; Zanatta, N.; Bonacorso, H. G.; Peppe, C.; Yuan, Y.-F. Tetrahedron Lett. 2004, 45, 8991.

  19. Gein, V. L.; Gein, L. F.; Tsypliakova, E. P.; Panova, O. S. Russ. J. Org. Chem. 2007, 43, 1382. [Zh. Org. Khim.2007, 43, 1386.]

  20. Gein, V. L.; Gorgopina, E. V.; Zamaraeva, T. M.; Dmitriev, M. V. Russ. J. Org. Chem.2017, 53, 1675. [Zh. Org. Khim.2017, 53, 1639.]

  21. Gan, X.; Fu, Z.; Liu, L.; Yan, Y.; Chen, C.; Zhou, Y.; Dong, J. Tetrahedron Lett. 2019, 60, 150906.

    Article  CAS  Google Scholar 

  22. CrysAlisPro, Version 1.171.37.33 (release 27-03-2014 CrysAlis171.NET); Agilent Technologies Ltd.: Yarnton.

  23. Palatinus, L.; Chapuis, G. J. Appl. Crystallogr.2007, 40, 786.

    Article  CAS  Google Scholar 

  24. Bourhis, L. J.; Dolomanov, O. V.; Gildea, R. J; Howard, J. A. K.; Puschmann, H. Acta Crystallogr., Sect. A: Found. Adv.2015, A71, 59.

  25. Sheldrick, G. M. Acta Crystallogr., Sect. A: Found. Crystallogr.2008, A64, 112.

  26. Sheldrick, G. M. Acta Crystallogr., Sect. C: Struct. Chem.2015, C71, 3.

  27. Dolomanov, O. V.; Bourhis, L. J.; Gildea, R. J.; Howard, J. A. K.; Puschman, H. J. Appl. Crystallogr.2009, 42, 339.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Perm State Pharmaceutical Academy, 2 Polevaya St., Perm, 614990, Russia

    Vladimir L. Gein, Tatiana M. Zamaraeva & Ekaterina V. Gorgopina

  2. Perm State University, 15 Bukireva St., Perm, 614990, Russia

    Maksim V. Dmitriev

Authors
  1. Vladimir L. Gein
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  2. Tatiana M. Zamaraeva
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  3. Ekaterina V. Gorgopina
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  4. Maksim V. Dmitriev
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Correspondence to Vladimir L. Gein.

Additional information

Supplementary information file containing 1H and 13C NMR spectra of compounds 1a–i, 2b, and 3 and crystallographic data of compounds 1d,h, 2b, and 3 is available at the journal website at http://link.springer.com/journal/10593.

Published in Khimiya Geterotsiklicheskikh Soedinenii, 2020, 56(3), 339–346

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Gein, V.L., Zamaraeva, T.M., Gorgopina, E.V. et al. A four-component Biginelli reaction: new opportunities for the synthesis of functionalized pyrimidines. Chem Heterocycl Comp 56, 339–346 (2020). https://doi.org/10.1007/s10593-020-02665-w

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  • DOI: https://doi.org/10.1007/s10593-020-02665-w

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