Abstract
In medicinal chemistry, the development of synthetic procedures for the access of new heterocyclic systems as potential scaffolds is elementary. Herein, we report our results on the formation of small drug-like heterocycles, utilizing flow chemistry. This approach enables the extension of the reaction parameter window, including high-pressure/high-temperature or hazardous chemistry. In our work, various novel condensed tricyclic benzothiazoles fused with furo- and thieno-rings were synthesized applying a multistep continuous-flow protocol. The process includes two ring closure steps and a nitro group reduction step. Batch and telescoped continuous-flow syntheses were also designed and performed.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Keserű, Gy.M.; Soós, T.; Kappe, C. O. Chem. Soc. Rev. 2014, 43, 5387–5399.
For selected examples of the application of continuous flow chemsitry, see: (a) McQuade, D. T.; Seeberger, P. H. J. Org. Chem. 2013, 78, 6384–6389
Yoshida, J.; Nagaki, A.; Yamada, D. Drug Discovery Today 2013, 10, e53–e59
Kirschneck, D. Chem. Eng. Tech. 2013, 36, 1061–1066
Schwalbe, T.; Autze, V.; Wille G. Chimia 2002, 56, 636–646.
Telvekar, V. N.; Bachhav, H. M.; Bairwa, V. K. Synlett 2012, 23, 2219–2222.
Le Bozec, L.; Moody, C. J. Aust. J. Chem. 2009, 62, 639–647.
Chao, Q.; Sprankle, K. G.; Grotzfeld, R. M. J. Med. Chem. 2009, 52, 7808–7816.
Hroch, L.; Aitken, L.; Benek, A. Current Med. Chem. 2015, 22, 730–747.
Kamal, A.; Syed, M. A. H.; Mohammed, S. M. Expert Opin. Ther. Pat. 2015, 25, 335–349.
For selected examples, see: (a) Abramenko, P. I.; Zhiryakov, V. G.; Ponomareva, T. K. Chem. Heterocycl. Compd. 1975, 11, 1361–1364
Preparation of condensed thiazoles as antibacterial agents. Haydon, D. J.; Czaplewski, L. G. from PCT Int. Appl. (2009), WO 2009074812 A1 Jun 18, 2009
Chakrabarty, M.; Kundu, T.; Arima, S.; Harigaya, Y. Tetrahedron Lett. 2005, 46, 2865–2868
Venkatraman, S. Bioorg. Med. Chem. 2013, 21, 2007–2017.
Nussbaumer, P.; Lehr, P.; Billich, A. J. Med. Chem. 2002, 45, 4310–4320.
Traven, V. F.; Podhaluzina, N. Y.; Vasilyev, A. V.; Manaev, A. V. ARKIVOC 2000, 6, 931–938.
Korthals, K. A.; Wulff, W. D. J. Am. Chem. Soc. 2008, 130, 2898–2899.
Aboraia A. S.; Yee S. W.; Gomaa, M. S.; Shah, N.; Robotham, A. C.; Makowski, B.; Prosser, D.; Brancale, A.; Jones, G.; Simons, C. Bioorg. Med. Chem. 2010, 18, 4939–4946.
Van Snick, W.; Aibuldinov, Y. K.; Dehaen, W. Tetrahedron 2013, 69, 4176–4184.
Kuznetsova, E. A.; Pryanishnikova, N. T.; Gaidukova, L. I.; Fedina, I. V.; Zhuravlev, S. V. Khim. Farm. Zhurnal 1975, 9, 11–15.
D’Sa, B. A.; Kisanga, P.; Verkade, J. G. Synlett 2001, 5, 670–672.
Matsunaga, N.; Kaku, T.; Itoh, F.; Tanaka, T.; Hara, T.; Miki, H.; Iwasaki, M.; Aono, T.; Yamaoka, M.; Kusaka, M.; Tasaka, A. Bioorg. Med. Chem. 2004, 12, 2251–2273.
Suzuki, T.; Tanemura, K.; Horaguchi, T.; Shimizu, T.; Sakakibara, T. J. Heterocyclic Chem. 1992, 29, 423–429.
Jones, R. V.; Godorhazy, L.; Varga, N.; Szalay, D.; Urge, L.; Darvas, F. J. Comb. Chem. 2006, 8, 110–116.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Rights and permissions
About this article
Cite this article
Lövei, K., Greiner, I., Éles, J. et al. Multistep Continuous-Flow Synthesis of Condensed Benzothiazoles. J Flow Chem 5, 74–81 (2015). https://doi.org/10.1556/1846.2015.00004
Published:
Issue Date:
DOI: https://doi.org/10.1556/1846.2015.00004