Synthetic route towards 1,2,3,4-tetrahydroquinoxaline/piperidine combined tricyclic ring system Scientific paper
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Abstract
The synthetic route toward novel tricyclic, nitrogen-containing system is disclosed. Three novel compounds possessing structural features of 1,2,3,4-tetrahydroquinoxaline and decahydropyrido[3,4-b]pyrazine are synthesized starting from readily available precursors in six or seven steps, of which the last three or four steps respectively are diastereoselective. Key reaction steps include N-acylation, Hofmann rearrangement and ring-closing Buchwald–Hartwig reaction. Compounds trans-8, cis-12 and trans-12 are synthesized in order to prove that this novel, tricyclic system can be functionalized with various groups. Synthetic significance of this heterocyclic system lies in the possibility for the orthogonal functionalization of three different amino groups, allowing fine structural tuning.
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References
B. Zhang, A. Studer, Chem. Soc. Rev. 44 (2015) 3505 (https://doi.org/10.1039/C5CS00083A)
T. Eicher, S. Hauptmann, A. Speicher, The Chemistry of Heterocycles: Structure, Reations, Syntheses, and Applications, Wiley-VCH Verlag GmbH & Co.,Weinheim, 2003 (https://doi.org/ 10.1002/352760183X)
E. Vitaku, D. T. Smith, J. T. Njardarson, J. Med. Chem. 57 (2014) 10257 (https://doi.org/10.1021/jm501100b)
N. Kerru, L. Gummidi, S. Maddila, K. K. Gangu, S. B. Jonnalagadda, Molecules 25 (2020) 1909 (https://doi.org/10.3390/molecules25081909)
S. Sabir, M. I. Alhazza, A. A. Ibrahim, Catal. Sustain. Energy 2 (2015) 99 (https://doi.org/10.1515/cse-2015-0009)
S. Tariq, K. Somakala, M. Amir, Eur. J. Med. Chem. 143 (2018) 542 (https://doi.org/10.1016/j.ejmech.2017.11.064)
V. A. Mamedov, N. A. Zhukova, Prog. Heterocyc. Chem. 24 (2012) 55 (https://doi.org/10.1016/B978-0-08-096807-0.00002-6)
R. Veligeti1, R. B. Madhu, J. Anireddy,V. R. Pasupuleti, V. K. R. Avula, K. S. Ethiraj, S. Uppalanchi, S. Kasturi1, Y. Perumal, H. S. Anantaraju, N. Polkam, M. R. Guda, S. Vallela, G. Vasilievich Zyryanov, Sci. Rep. 10 (2020) 20720 (https://doi.org/10.1038/s41598-020-77590-1)
K. Torisu, K. Kobayashi, M. Iwahashi, Y. Nakai, T. Onoda, T. Nagase, I. Sugimoto, Y. Okada, R. Matsumoto, F. Nanbu, S. Ohuchida, H. Nakao, M. Toda, Bioorg. Med. Chem. 12 (2004) 5361 (https://doi.org/10.1016/j.bmc.2004.07.048)
C. T. Eary, Z. S. Jones, R. D. Groneberg, L. E. Burgess, D. A. Mareska, M. D. Drew, J. F. Blake, E. R. Laird, D. Balachari, M. OSullivan, A. Allen, V. Marsh, Bioorg. Med. Chem. Lett. 17 (2007) 2608 (https://doi.org/10.1016/j.bmcl.2007.01.112)
J. J. Chen, W. Qian, K. Biswas, V. N. Viswanadhan, B. C. Askew, S. Hitchcock, R. W. Hungate, L. Arik, E. Johnson, Bioorg. Med. Chem. Lett. 18 (2008) 4477 (https://doi.org/10.1016/j.bmcl.2008.07.055)
G. Morissette, J. P. Fortin, S. Otis, J. Bouthillier, F. Marceau, J. Pharmacol. Exp. Ther. 311 (2004) 1121 (https://doi.org/10.1124/jpet.104.071266)
Y. Ohtake, A. Naito, H. Hasegawa, K. Kawano, D. Morizono, M. Taniguchi, Y. Tanaka, H. Matsukawa, K. Naito, T. Oguma, Y. Ezure, Y. Tsuriya, Bioorg. Med. Chem. 7 (1999) 1247 (https://doi.org/10.1016/S0968-0896(99)00049-8)
A. Patti, S. Pedotti, Tetrahedron 66 (2010) 5607 (https://doi.org/10.1016/j.tet.2010.05.090)
R. Rahi, M. Fang, A. Ahmed, R. A. Sánchez-Delgado, Dalton. Trans. 41 (2012) 14490 (https://doi.org/10.1039/C2DT31533E)
W. Tang, L. Xu, Q. H. Fan, J. Wang, B. Fan, Z. Zhou, K. H. Lam, A.S.C. Chan, Angew. Chem. Int. Ed. 48 (2009) 9135 (https://doi.org/10.1002/anie.200904518)
B. B. F. Mirjalili, A. Akbari, Chin. Chem. Lett. 22 (2011) 753 (https://doi.org/10.1016/j.cclet.2010.12.016)
C. S. Cho, W. X. Ren, S. C. Shim, Tetrahedron Lett. 48 (2007) 4665 (https://doi.org/10.1016/j.tetlet.2007.05.044)
F. Pan, T. M. Chen, J. J. Cao, J. P. Zou, W. Zhang, Tetrahedron Lett. 53 (2012) 2508 (https://doi.org/10.1016/j.tetlet.2012.02.113)
M. J. Climent, A. Corma, J. C. Hernández, A. B. Hungría, S. Iborra, S. Martínez-Silvestre, J. Catal. 292 (2012) 118 (https://doi.org/10.1016/j.jcat.2012.05.002)
K. C. Majumdar, K. Ray, S. Ponra, Tetrahedron Lett. 51 (2010) 5437 (https://doi.org/10.1016/j.tetlet.2010.08.016)
R. A. Bunce, D. M. Herron, L. Y. Hale, J. Heterocycl. Chem. 40 (2003) 1031 (https://doi.org/10.1002/jhet.5570400611)
R. A. Bunce, D. M. Herron, M. L. Ackerman, J. Org. Chem. 65 (2000) 2847 (https://doi.org/10.1021/jo991899+)
S.-C. Yang, P.-C. Liu, W.-H. Feng, Tetrahedron Lett. 45 (2004) 4951 (https://doi.org/10.1016/j.tetlet.2004.04.140)
R. Mukhopadhyay, N. G. Kundu, Synlett (2001) 1143 (https:/doi.org/10.1055/s-2001-15135)
M. K. Ghorai, A. K. Sahoo, S. Kumar, Org. Lett. 13 (2011) 5972 (https://doi.org/10.1021/ol2023906)
V. Krchnak, J. Smith, J. Vagner, Tetrahedron Lett. 42 (2001) 2443 (https://doi.org/10.1016/S0040-4039(01)00197-6)
E. Merişor, J. Conrad, I. Klaiber, S. Mika, U. Beifuss, Angew. Chem. Int. Ed. 46 (2007) 3353 (https://doi.org/10.1002/anie.200605260)
Y. Fu, J. Y. Wang, W. G. Chen, Y. Li, L. X. Zhao, S. Gao, F. Ye, Heterocycl. Chem. 54 (2017) 3023 (https://doi.org/10.1002/jhet.2911)
S. Liu, Y. Zhou, Y. Sui, H. Liu, H. Zhou, Org. Chem. Front. 4 (2017) 2175 (https://doi.org/10.1039/C7QO00604G)
G. Oshiro, A. Wojdan, M. Klein, G. Metcalf, J. Cardiovasc. Pharmacol. 10 (1987) 341 (https://doi.org./ 10.1097/00005344-198709000-00014)
I. Jirkovsky, G. Santroch, R. Baudy, G. Oshiro, J. Med. Chem. 30 (1987) 388 (https://doi.org/10.1021/jm00385a022)
A. Nurgiin, C. François, (Sanofi Aventis France) EP0287468A2 (1988)
M. Królikiewicz, K. Błaziak, W. Danikiewicz, Z. Wróbel, Synlett 24 (2013) 1945 (https://doi.org/10.1055/s-0033-1339467)
I. I. Jevtić, Lj. Došen-Mićović, E. R. Ivanović, N. M. Todorović, M. D. Ivanović, Synthesis 49 (2017) 3126 (https://doi.org/ 10.1055/s-0036-1588985)
I. I. Jevtić, K. Savić Vujović, D. Srebro, S. Vučković, M. D. Ivanović, S. V. Kostić-
-Rajačić, Pharmacol. Rep. 72 (2020) 1069 (https://doi.org/ 10.1007/s43440-020-00121-2)
J. Popović-Djordjević, S. Stepanović, Lj. Došen-Mićović, E. Ivanović, M. D. Ivanović, Green Chem. Lett. Rev. 9 (2016) 61 (https://doi.org/ 10.1080/17518253.2016.1145744)
P. G. M. Wuts, Greenes Protective Groups in Organic Synthesis, 5th ed., John Wiley & Sons, Inc., Hoboken, NJ, 2014, pp. 895–4045 (https://doi.org/10.1002/9781118905074)
I. I. Jevtić, Lj. Došen-Mićović, E. R. Ivanović, M. D. Ivanović. Synthesis 48 (2016) 1550 (https://doi.org/ 10.1055/s-0035-1561405)
R. Dorel, C. P. Grugel, A. M. Haydl, Angew. Chem. Int. Ed. 58 (2019) 17118 (https://doi.org/10.1002/anie.201904795).