Diversified Synthesis of 2-(4-Oxo[1,2,3]triazolo[1,5-a]quinoxalin-5(4H)-yl)acetamide Derivatives through Ugi-4-CR and Copper-Catalyzed Tandem Reactions

^§ These authors contributed equally.

Abstract

A diversified synthesis of 2-(4-oxo[1,2,3]triazolo-[1,5-a]quin­oxalin-5(4H)-yl)acetamide derivatives is demonstrated. The protocol employs a Ugi four-component reaction for the assembling of N-(2-haloaryl)propynamide intermediates and followed by a copper-catalyzed tandem reaction of the synthetic N-(2-haloaryl)propynamides with sodium azide. Such a method provides rapid access to structurally varied and complex fused tricyclic scaffolds through readily available starting materials.

Key words

diversified synthesis - Ugi reaction - copper-catalyzed - tandem reaction - fused heterocycles

• References

• 1a Quin LD. Tyrell J. Fundamentals of Heterocyclic Chemistry: Importance in Nature and in the Synthesis of Pharmaceuticals. Wiley; Chichester: 2010
• 1b Joule JA. Mills K. Heterocyclic Chemistry . 5th ed. Wiley; Chichester: 2010
• 2 Witherup KM. Ransom RW. Graham AC. Bernard AM. Salvatore MJ. Lumma WC. Anderson PS. Pitzenberger SM. Varga SL. J. Am. Chem. Soc. 1995; 117: 6682
• 3a Mohr JT. Stoltz BM. Chem. Asian J. 2007; 2: 1476
• 3b Hong AY. Stoltz BM. Eur. J. Org. Chem. 2013; 2745
• 3c Yokoyama Y. Kondo K. Mitsuhashi M. Murakami Y. Tetrahedron Lett. 1996; 37: 9309
• 3d Yamada F. Makita Y. Somei M. Heterocycles 2007; 72: 599
• 4 Shen HC. Ding F.-X. Deng QL. Wilsie LC. Krsmanovic ML. Taggart AK. Carballo-Jane E. Ren N. Cai T.-Q. Wu T.-J. Wu KK. Cheng K. Chen Q. Wolff MS. Tong XC. Holt TG. Waters MG. Hammond ML. Tata JR. Colletti SL. J. Med. Chem. 2009; 52: 2587
• 5a Biagi G. Giorgi I. Livi O. Scartoni V. Betti L. Giannaccini G. Trincavelli ML. Eur. J. Med. Chem. 2002; 37: 565
• 5b Bertelli L. Biagi G. Giorgi I. Manera C. Livi O. Scarton V. Betti L. Giannaccini G. Trincavelli L. Barili PL. Eur. J. Med. Chem. 1998; 33: 113
• 6a Leach CA. Brown TH. Ife RJ. Keeling DJ. Laing SM. Parsons ME. Price CA. Wiggall KJ. J. Med. Chem. 1992; 35: 1845
• 6b Escolano C. Jones K. Tetrahedron Lett. 2000; 41: 8951
• 6c Brown TH. Ife RJ. Keeling DJ. Laing SM. Leach CA. Parsons ME. Price CA. Reavill DR. Wiggall KJ. J. Med. Chem. 1990; 33: 527
• 7 Suzuki F. Kuroda T. Nakasato Y. Manabe H. Ohmori K. Kitamura S. Ichikawa S. Ohno T. J. Med. Chem. 1992; 35: 4045
• 8 Schreiber SL. Burke MD. Angew. Chem. Int. Ed. 2004; 43: 46
• 9 Yan J. Zhou F. Qin D. Cai T. Ding K. Cai Q. Org. Lett. 2012; 14: 1262
• 10 For a recent review, see: Wei F. Wang W. Ma Y. Tung C.-H. Xu Z. Chem. Commun. 2016; 52: 14188

For examples to trap organocuprates with electrophiles, see:
• 11a Wu Y.-M. Deng J. Li Y. Chen Q.-Y. Synthesis 2005; 1314
• 11b Li L. Zhang G. Zhu A. Zhang L. J. Org. Chem. 2008; 73: 3630
• 11c Zhang X. Hsung RP. Li H. Chem. Commun. 2007; 2420
• 11d Wei F. Li H. Song C. Ma Y. Zhou L. Tung C.-H. Xu Z. Org. Lett. 2015; 17: 2860

For examples of tandem CuAAC/oxidative coupling reactions, see:
• 12a Selvaraju M. Sun C.-M. Adv. Synth. Catal. 2014; 356: 1329
• 12b Gomes AT. P. C. Martins PR. C. Rocha DR. Neves MG. P. M. S. Ferreira VF. Silva AM. S. Cavaleiro JA. S. da Silva F. deC. Synlett 2013; 41
• 12c Krishna PM. Ramachary DB. Peesapati S. RSC Adv. 2015; 5: 62062
• 12d Wang W. Peng X. Wei F. Tung C.-H. Xu Z. Angew. Chem. Int. Ed. 2016; 55: 649
• 12e Li L. Hao G. Zhu A. Fan X. Zhang G. Zhang L. Chem. Eur. J. 2013; 19: 14403
• 12f Alonso F. Moglie Y. Radivoy G. Yus M. Synlett 2012; 24: 2179
• 12g Yang D. Fu N. Liu Z. Li Y. Chen B. Synlett 2007; 278
• 12h Li L. Fan X. Zhang Y. Zhu A. Zhang G. Tetrahedron 2013; 69: 9939
• 12i Wang W. Wei F. Ma Y. Tung C.-H. Xu Z. Org. Lett. 2016; 18: 4158
• 13 Ugi I. Lohberger S. Karl R. Comprehensive Organic Synthesis; Part 2, Vol. 2. Trost BM. Fleming I. Pergamon Press; New York: 1991: 1083
• 14a Orru RV. A. de Greef M. Synthesis 2003; 1471
• 14b Hoesl CE. Nefzi A. Houghten RA. J. Comb. Chem. 2003; 5: 155
• 15 Zhou F. Liu J. Ding K. Liu J. Cai Q. J. Org. Chem. 2011; 76: 5346