Synthesis of Pyrido[3,4-c][1,9]phenanthroline – A Five-Step Procedure to a Novel N-Containing Ring Skeleton

Abstract

The condensation of paraformaldehyde with two equivalents of 4-methylpyridine-3-carbonitrile under basic conditions afforded 6-amino-11,12-dihydropyrido[3,4-c][1,9]phenanthroline, which was converted via the corresponding 6-oxo- and 6-chloro derivatives­ and a dehalogenation into 11,12-dihydropyrido[3,4-c][1,9]phenanthroline. The fully aromatized derivative pyrido[3,4-c][1,9]phenanthroline was obtained in an ultimate dehydrogenation procedure.

Key words

antitumor agents - condensation - dehydrogenation - heterocycles - phenanthrolines - ring closure

• References

• 1a Pommier Y. Nat. Rev. Cancer 2006; 6: 789
• 1b Pommier Y. Chem. Rev. 2009; 109: 2894
• 1c Li T.-K, Houghton PJ. Cancer Res. 2003; 63: 8400
• 1d Simeon S, Rios JL, Villar A. Pharmazie 1989; 44: 593
• 2 Berg SS. J. Chem. Soc. 1963; 3635
• 3 Sliwa W, Szulc Z. J. Prakt. Chem. 1977; 319: 362
• 4 Mortier J, Castanet A.-S, Belaud-Rotureau M. Int. Patent WO2011101599A1, 2011
• 5 Nutaitis CF. Org. Prep. Proced. Int. 2007; 39: 611
• 6 Meier C, Kotthaus J, Stenzel L, Girreser U, Heber D, Clement B. Tetrahedron 2012; 68: 9105
• 7a Kock I, Heber D, Weide M, Wolschendorf U, Clement B. J. Med. Chem. 2005; 48: 2772
• 7b Clement B, Weide M, Wolschendorf U, Kock I. Angew. Chem. Int. Ed. 2005; 44: 635
• 8a Kock I. Ph.D. Dissertation . Christian Albrechts University of Kiel; Germany: 2003
• 8b Kornblum N. Org. React. 1944; 2: 262
• 9a Engel A In Houben-Weyl, Methods of Organic Chemistry . Vol. E 16a, Part II. Klamann D. Thieme; Stuttgart: 1990: 1052
• 9b Theobald RS, Schofield K. Chem. Rev. 1950; 46: 171
• 9c Keene B, Tissington P. Adv. Heterocycl. Chem. 1971; 13: 315
• 10 Zur Nieden D. Ph.D. Dissertation . Christian Albrechts University of Kiel; Germany: 2007
• 11 Cailly T, Fabis F, Legay R, Oulyadi H, Rault S. Tetrahedron 2006; 63: 71