Table of Contents
ISRN Organic Chemistry
Volume 2014 (2014), Article ID 621592, 10 pages
http://dx.doi.org/10.1155/2014/621592
Research Article

Efficient Electrochemical N-Alkylation of N-Boc-Protected 4-Aminopyridines: Towards New Biologically Active Compounds

1Department of Basic and Applied Sciences for Engineering, Sapienza University of Rome, Via Castro Laurenziano 7, 00161 Rome, Italy
2Department of Public Health and Infectious Diseases, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy
3Laboratory for Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Antwerp University, 2610 Antwerp, Belgium
4“Istituto Pasteur-Fondazione Cenci Bolognetti”, Department of “Chimica e Tecnologie del Farmaco”, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy

Received 22 November 2013; Accepted 21 January 2014; Published 5 March 2014

Academic Editors: L. Palombi and R. Pohl

Copyright © 2014 Marta Feroci et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. G. R. Luedtke, K. Schinzel, X. Tan et al., “Amide-based inhibitors of p38α MAP kinase. Part 1. Discovery of novel N-pyridyl amide lead molecules,” Bioorganic and Medicinal Chemistry Letters, vol. 20, no. 8, pp. 2556–2559, 2010. View at Publisher · View at Google Scholar · View at Scopus
  2. M. Otsuka, M. Fujita, Y. Sugiura et al., “Synthetic inhibitors of regulatory proteins involved in the signaling pathway of the replication of human immunodeficiency virus 1,” Bioorganic and Medicinal Chemistry, vol. 5, no. 1, pp. 205–215, 1997. View at Publisher · View at Google Scholar · View at Scopus
  3. H. Nishida, Y. Miyazaki, T. Mukaihira et al., “Synthesis and evaluation of 1-arylsulfonyl-3-piperazinone derivatives as a factor Xa inhibitor II. Substituent effect on biological activities,” Chemical and Pharmaceutical Bulletin, vol. 50, no. 9, pp. 1187–1194, 2002. View at Publisher · View at Google Scholar · View at Scopus
  4. C. A. Willoughby, K. G. Rosauer, J. J. Hale et al., “1,3,4 Trisubstituted pyrrolidine CCR5 receptor antagonists bearing 4-aminoheterocycle substituted piperidine side chains,” Bioorganic and Medicinal Chemistry Letters, vol. 13, no. 3, pp. 427–431, 2003. View at Publisher · View at Google Scholar · View at Scopus
  5. D. de Vita, L. Scipione, S. Tortorella et al., “Synthesis and antifungal activity of a new series of 2-(1H-imidazol-1-yl)- 1-phenylethanol derivatives,” European Journal of Medicinal Chemistry, vol. 49, pp. 334–342, 2012. View at Publisher · View at Google Scholar · View at Scopus
  6. L. Friggeri, L. Scipione, R. Costi et al., “New promising compounds with in vitro nanomolar activity against Trypanosoma Cruzi,” Medicinal Chemistry Letters, vol. 4, pp. 538–541, 2013. View at Google Scholar
  7. C. K. Chen, P. S. Doyle, L. V. Yermalitskaya et al., “Trypanosoma Cruzi CYP51 inhibitor derived from a Mycobacterium tuberculosis screen hit,” PLoS Neglected Tropical Diseases, vol. 3, no. 2, article e372, 2009. View at Publisher · View at Google Scholar · View at Scopus
  8. T. Y. Hargrove, Z. Wawrzak, P. W. Alexander et al., “Complexes of Trypanosoma Cruzi Sterol 14α-Demethylase (CYP51) with two pyridine-based drug candidates for chagas disease: structural basis for pathogen selectivity,” Journal of Biological Chemistry, vol. 288, pp. 31602–31615, 2013. View at Google Scholar
  9. Q. Xu, Q. Li, X. Zhu, and J. Chen, “Green and scalable aldehyde-catalyzed transition metal-freeDehydrative N-Alkylation of amides and amines with alcohols,” Advanced Synthesis and Catalysis, vol. 355, pp. 73–80, 2013. View at Google Scholar
  10. Q. Li, S. Fan, Q. Sun, H. Tian, X. Yu, and Q. Xu, “Copper-catalyzed N-alkylation of amides and amines with alcohols employing the aerobic relay race methodology,” Organic and Biomolecular Chemistry, vol. 10, no. 15, pp. 2966–2972, 2012. View at Publisher · View at Google Scholar · View at Scopus
  11. A. Martínez-Asencio, D. J. Ramón, and M. Yus, “N-Alkylation of poor nucleophilic amines and derivatives with alcohols by a hydrogen autotransfer process catalyzed by copper(II) acetate: scope and mechanistic considerations,” Tetrahedron, vol. 67, no. 17, pp. 3140–3149, 2011. View at Publisher · View at Google Scholar · View at Scopus
  12. R. Martínez, D. J. Ramón, and M. Yus, “Selective N-monoalkylation of aromatic amines with benzylic alcohols by a hydrogen autotransfer process catalyzed by unmodified magnetite,” Organic and Biomolecular Chemistry, vol. 7, no. 10, pp. 2176–2181, 2009. View at Publisher · View at Google Scholar · View at Scopus
  13. E. J. Delaney, L. E. Wood, and I. M. Klotz, “Poly(ethylenimines) with alternative (alkylamino)pyridines as nucleophilic catalysts,” Journal of the American Chemical Society, vol. 104, no. 3, pp. 799–807, 1982. View at Google Scholar · View at Scopus
  14. T. Zhao and G. Sun, “Synthesis and characterization of antimicrobial cationic surfactants: aminopyridinium salts,” Journal of Surfactants and Detergents, vol. 9, no. 4, pp. 325–330, 2006. View at Publisher · View at Google Scholar · View at Scopus
  15. T. Ito, T. Ikemoto, Y. Isogami et al., “Practical synthesis of low-density lipoprotein receptor upregulator, N-[1-(3-phenylpropane-1-yl)piperidin-4-yl]-5-thia-1,8b-diazaacenaphthylene-4-carboxamide,” Organic Process Research and Development, vol. 6, no. 3, pp. 238–241, 2002. View at Publisher · View at Google Scholar · View at Scopus
  16. O. M. Singh, S. J. Singh, N. K. Su, and S.-G. Lee, “Reaction of lithioamines with alkyl halides: a convenient direct synthesis of N-alkylaminopyridines,” Bulletin of the Korean Chemical Society, vol. 28, no. 1, pp. 115–117, 2007. View at Google Scholar · View at Scopus
  17. D. M. Krein and T. L. Lowary, “A convenient synthesis of 2-(alkylamino)pyridines,” Journal of Organic Chemistry, vol. 67, no. 14, pp. 4965–4967, 2002. View at Publisher · View at Google Scholar · View at Scopus
  18. The direct cathodic reduction of N-Boc-4AP led to its deprotection and to the formation of 4AP.
  19. L. Rossi, M. Feroci, and A. Inesi, “The electrogenerated cyanomethyl anion in organic synthesis,” Mini-Reviews in Organic Chemistry, vol. 2, no. 1, pp. 79–90, 2005. View at Publisher · View at Google Scholar · View at Scopus
  20. M. Feroci, D. de Vita, L. Scipione, G. Sotgiu, and S. Tortorella, “Electrogenerated acetonitrile anion induced selective N-alkylation of bifunctional compounds,” Tetrahedron Letters, vol. 53, no. 20, pp. 2564–2567, 2012. View at Publisher · View at Google Scholar · View at Scopus
  21. M. Feroci, I. Chiarotto, L. Rossi, and A. Inesi, “Activation of elemental sulfur by electrogenerated cyanomethyl anion: synthesis of substituted 2-aminothiophenes by the Gewald reaction,” Advanced Synthesis and Catalysis, vol. 350, no. 17, pp. 2740–2746, 2008. View at Publisher · View at Google Scholar · View at Scopus
  22. M. Feroci, “Synthesis of β-lactams by 4-exo-tet cyclization process induced by electrogenerated cyanomethyl anion, part 2. Stereochemical implications,” Advanced Synthesis and Catalysis, vol. 349, no. 13, pp. 2177–2181, 2007. View at Publisher · View at Google Scholar · View at Scopus
  23. M. Feroci, M. A. Casadei, M. Orsini, L. Palombi, and A. Inesi, “Cyanomethyl anion/carbon dioxide system: an electrogenerated carboxylating reagent. Synthesis of carbamates under mild and safe conditions,” Journal of Organic Chemistry, vol. 68, no. 4, pp. 1548–1551, 2003. View at Publisher · View at Google Scholar · View at Scopus
  24. M. Feroci, M. Orsini, G. Sotgiu, L. Rossi, and A. Inesi, “Electrochemically promoted C-N bond formation from acetylenic amines and CO2. Synthesis of 5-methylene-1,3-oxazolidin-2-ones,” Journal of Organic Chemistry, vol. 70, no. 19, pp. 7795–7798, 2005. View at Publisher · View at Google Scholar · View at Scopus
  25. Y. Basel and A. Hassner, “Di-tert-butyl dicarbonate and 4-(dimethylamino)pyridine revisited. Their reactions with amines and alcohols,” Journal of Organic Chemistry, vol. 65, no. 20, pp. 6368–6380, 2000. View at Publisher · View at Google Scholar · View at Scopus
  26. CLSI, Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts, Approved Standard, 3rd edition. CLSI Document M27A3, Clinical and Laboratory Standards Institute, Wayne, Pa, USA, 2008.
  27. CLSI, Reference Method for Broth Dilution Antifungal Susceptibility Testing of Filamentous Fungi, Approved Standard, 2nd edition. CLSI Document M38-A2, Clinical and Laboratory Standards Institute, Wayne, Pa, USA, 2008.
  28. CLSI, Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts, 3rd inFormational Supplement. CLSI Document M27-S3, Clinical and Laboratory Standards Institute, Wayne, Pa, USA, 2008.
  29. P. Cos, A. J. Vlietinck, D. V. Berghe, and L. Maes, “Anti-infective potential of natural products: how to develop a stronger in vitro 'proof-of-concept',” Journal of Ethnopharmacology, vol. 106, no. 3, pp. 290–302, 2006. View at Publisher · View at Google Scholar · View at Scopus