One-Pot Synthesis of Imidazopyridine Derivatives

Abstract

Two highly efficient and general one-pot annulation reactions are described for the synthesis of imidazopyridine derivatives (IPs). The two procedures are complementary to each other: Whereas the first one allows the production of simpler IPs, the second leads to IPs with functionalized imidazole moiety. Both methodologies consist of an activation step, which raises the electrophilicity of the N-heterocyclic starting material (i.e., quaternarization of the N-heterocycle), followed by a cascade reaction involving nucleophilic addition, substitution, rearrangement, and oxidation steps. These methodologies can be used in the synthesis of a library of drug-like molecules.

Key words

annulation reaction - one-pot reaction - cascade reaction - N-heterocycles - imidazole derivatives

References

• 1 Comprehensive Heterocyclic Chemistry   Vol. 4:  Katritzky AR. Rees CW. Pergamon Press; New York: 1984.  p.1-38  
• 2 Tietze LF. Chem. Rev.  1996,  96:  115 
• 3 Pellisier H. Tetrahedron  2006,  62:  1619 
• 4 Enders D. Grondal C. Hüttl MRM. Angew. Chem. Int. Ed.  2007,  46:  1570 
• 5 Nicolaou KC. Edmonds DJ. Bulger PG. Angew. Chem. Int. Ed.  2006,  45:  7134 
• 6 Parenty ADC. Guthrie KM. Song Y.-F. Smith LV. Burkholder E. Cronin L. Chem. Commun.  2006,  1194 
• 7 Parenty ADC. Song Y.-F. Richmond CJ. Cronin L. Org. Lett.  2007,  9:  2253 
• 8 Parenty ADC. Smith LV. Pickering AL. Long DL. Cronin L. J. Org. Chem.  2004,  69:  5934 
• 9 Parenty ADC. Smith LV. Cronin L. Tetrahedron  2005,  61:  8410 
• 10a Tóth J. Nedves A. Dancsó A. Blaskó G. Tke L. Nyerges M. Synthesis  2007,  1003 
• 10b Krauze A. Vitolina R. Garaliene V. Sile L. Klusa V. Duburs G. Eur. J. Med. Chem.  2005,  40:  1163 
• 10c Fang X. Wu YM. Deng J. Wang SW. Tetrahedron  2004,  60:  5487 
• 11a Zincke T. Justus Liebigs Ann. Chem.  1903,  330:  361 
• 11b Zincke T. Justus Liebigs Ann. Chem.  1904,  333:  296 
• 11c Zincke T. Wurker W. Justus Liebigs Ann. Chem.  1905,  338:  107 
• 12 Kearney AM. Vanderwal CD. Angew. Chem. Int. Ed.  2006,  45:  7803