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

Huy V. Huynh; Selçuk Çalimsiz; Hilaire V. Kemami Wangun; Trevor J. Rainey; Teague M. McGinitie; Xiaoming Liao; Lizhi Yu

doi:10.1055/s-0037-1609345

Synthesis, Table of Contents

Synthesis 2018; 50(11): 2221-2230
DOI: 10.1055/s-0037-1609345

paper

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

Huy V. Huynh*

^aDepartment of Process Chemistry, Gilead Alberta ULC, 1021 Hayter Road NW, Edmonton, Alberta T6S 1A1, Canada

,

Selçuk Çalimsiz

^aDepartment of Process Chemistry, Gilead Alberta ULC, 1021 Hayter Road NW, Edmonton, Alberta T6S 1A1, Canada

,

Hilaire V. Kemami Wangun

^bDepartment of Analytical Chemistry, Gilead Alberta ULC, 1021 Hayter Road NW, Edmonton, Alberta T6S 1A1, Canada

,

Trevor J. Rainey

^cDepartment of Process Chemistry, Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94404, USA

,

Teague M. McGinitie

^bDepartment of Analytical Chemistry, Gilead Alberta ULC, 1021 Hayter Road NW, Edmonton, Alberta T6S 1A1, Canada

,

Xiaoming Liao

^dDepartment of Process Development and Manufacturing, Pharmaron Beijing, Co. Ltd., 6 Tai-He Road, BDA, Beijing, 100176, P. R. of China Email: Huy.Huynh@gilead.com

,

Lizhi Yu

^dDepartment of Process Development and Manufacturing, Pharmaron Beijing, Co. Ltd., 6 Tai-He Road, BDA, Beijing, 100176, P. R. of China Email: Huy.Huynh@gilead.com

› Author Affiliations

Abstract

All articles of this category

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

Full Text

References

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

Supplementary Material

Supporting Information