An Aniline-Mediated Regioselective Synthesis of Quinoxalin-2-ones via the Condensation of α-Ketimine Esters with 2-Aminoanilines

Abstract

A highly regioselective method for the condensation of α-ketimine esters with 2-aminoanilines for the construction of quinoxalin-2-one derivatives is described. The substrate scope with 2-aminoaniline derivatives and different α-keto esters is explored with yields ranging from 44 to 90% and typical isolated regioselectivities between 6.4 to >25:1.

Key words

quinoxalin-2-ones - 2-aminoanilines - α-ketimine esters - one-pot synthesis - transimination - regioselectivity

• References

• 1a Kotharkar SA. Shinde DB. Bioorg. Med. Chem. Lett. 2006; 16: 6181
• 1b Brown DJ. Taylor EC. Wipf P. The Chemistry of Heterocyclic Compounds, Quinoxalines: Supplement II . John Wiley and Sons; Hoboken: 2004
• 1c Hui X. Desrivot J. Bories C. Loisea PM. Franck X. Hocquemiller R. Figadere B. Bioorg. Med. Chem. Lett. 2006; 16: 815
• 2 Rodrigues FA. R. Bomfirm I da S. Cavalcanti BC. Pessoa C do Ó. Wardell JL. Wardell SM. S. V. Pinheiro AC. Kaiser CR. Nogueira TC. M. Low JN. Gomes LR. de Souza MV. N. Bioorg. Med. Chem. Lett. 2014; 24: 934
• 3 Loriga M. Piras S. Sanna P. Paglietti G. Farmaco 1997; 52: 157
• 4 Parhi AK. Zhang Y. Saionz KW. Pradhan P. Kaul M. Trivedi K. Pilch DS. LaVoie EJ. Bioorg. Med. Chem. Lett. 2013; 23: 4968
• 5 Guillon J. Morea S. Mouray E. Sinou V. Forfar I. Fabre SB. Desplat V. Millet P. Parzy D. Jarry C. Grellier P. Bioorg. Med. Chem. 2008; 16: 9133
• 6 Thomas KR. J. Velusamy M. Lin JT. Chuen C.-H. Tao Y.-T. Chem. Mater. 2005; 17: 1860
• 7a Shi J. Chai Z. Su J. Chen J. Tang R. Fan K. Zhang L. Han H. Qin J. Peng T. Li Q. Li Z. Dyes Pigments 2013; 98: 405
• 7b Li H. Koh TM. Hagfeldt A. Gratzel M. Mhaisalkar SG. Grimsdale AC. Chem. Commun. 2013; 49: 2409
• 7c Venkateswararao A. Tyagi P. Thomas KR. J. Chen PW. Ho KC. Tetrahedron 2014; 70: 6318
• 8 Dailey S. Feast JW. Peace RJ. Sage IC. Till S. Wood EL. J. Mater. Chem. 2001; 11: 2238
• 9 Saravanakumar S. Kindermann MK. Heinicke J. Kockerling M. Chem. Commun. 2006; 640
• 10a Rosner M. Billhardt-Troughton U.-M. Kirsh R. Kleim J.-P. Meichsner C. Riess G. Winkler I. US5723461A, 1998
• 10b El-Sabbagh OI. El-Sadek ME. Lashine SM. Yassin SH. S. El-Nabtity M. Med. Chem. Res. 2009; 18: 782
• 11 Rooney TP. C. Filippakopoulos P. Fedorov O. Picaud S. Cortopassi WA. Hay DA. Martin S. Tumber A. Rogers CM. Philpott M. Wang M. Thompson AL. Heightman TD. Pryde DC. Cook A. Paton RS. Müller S. Knapp S. Brennan PE. Conway SJ. Angew. Chem. Int. Ed. 2014; 53: 6126
• 12a Bjornson K. Canales E. Cottell JJ. Karki KK. Katana AA. Kato D. Kobayashi T. Link JO. Martinez R. Phillips BW. Pyun H.-J. Sangi M. Schrier AJ. Siegel D. Taylor JG. Tran CV. Trejo MT. A. Vivian RW. Yang Z.-Y. Zablocki J. Zipfel S. WO2014008285 A1, 2014
• 12b Nakajima S. Sun Y. Tang D. Xu G. Porter B. Or YS. Wang Z. Miao Z. WO2004093798 A2, 2004
• 12c Cagulada A. Chan J. Chan L. Colby DA. Karki KK. Kato D. Keaton KA. Kondapally S. Levins C. Littke A. Martinez R. Pcion D. Reynolds T. Ross B. Sangi M. Schrier AJ. Seng P. Siegel D. Shapiro N. Tang D. Tayler JG. Tripp J. Waltman AW. Yu L. US2015/0175626 A1, 2015
• 12d Bringley D. Chan J. Fung P. Keaton K. Lapina O. Morrison H. Pcion D. US2015/0175625 A1, 2015
• 13a Ostrowska K. Szymoniak K. Szczurek M. Jamrozy K. Rapala-Kozik M. Tetrahedron 2011; 67: 5219
• 13b Meyer C. Zapoli’skii VA. Adam AE. W. Kaufmann DE. Synthesis 2008; 2575
• 13c Grable S. Vanderheiden S. Hodapp P. Bulat B. Nieger M. Jung N. Brase S. Org. Lett. 2016; 18: 3598
• 13d Korin E. Cohen B. Bai Y. Zeng C. Becker BY. Tetrahedron 2012; 68: 7450
• 14 Shen J. Wang X. Lin X. Yang Z. Cheng G. Cui X. Org. Lett. 2016; 18: 1378
• 15 Rustagi V. Tiwari R. Verma AK. Eur. J. Org. Chem. 2012; 24: 4590
• 16 Yi CS. Yun SY. J. Am. Chem. Soc. 2005; 127: 17000
• 17 Mukherjee C. Watanabe KT. Biehl ER. Tetrahedron Lett. 2012; 53: 6008
• 18 Shi GQ. Cao ZY. Cai W.-L. Tetrahedron 1995; 51: 5011
• 19a Jaguar, version 9.3, Schrodinger Inc., New York, 2016;
• 19b Bochevarov AD. Harder E. Hughes TF. Greenwood JR. Braden DA. Philipp DM. Rinaldo D. Halls MD. Zhang J. Friesner RA. Int. J. Quantum Chem. 2013; 113: 2110
• 20 Venable JD. Kindrachuk DE. Peterson ML. Edwards JP. Tetrahedron Lett. 2010; 51: 337
• 21 Mason JC. Tennant G. J. Chem. Soc., Chem. Commun. 1971; 11: 586