Preparation of Novel 2,3,8-Trisubstituted Pyrido[3,4-b]pyrazines and Pyrido[2,3-b]pyrazines

Abstract

A four-step synthesis of 8-bromo-2,3-disubstituted pyrido[3,4-b]pyrazines and a six-step synthesis of 8-amino-2,3-disubstituted pyrido[3,4-b]pyrazines have been developed. A particularly valuable feature of this synthetic route is the possibility to build 2,3-disubstituted pyrido[3,4-b]pyrazines with a large variety of substituents in position 8 (aniline, amide, urea, thiourea). Our protocol was extended to the synthesis of 2,3,8-trisubstituted pyrido[2,3-b]pyrazines.

Key words

pyrido[3,4-b]pyrazine - pyrido[2,3-b]pyrazine - di­amino­pyridine - urea - thiourea - amide

References

• 1 Koch P. Jahns H. Schattel V. Goettert M. Laufer S. J. Med. Chem.  2010,  53:  1128 
• 2 Claus E, Seipelt I, Günther E, Polymeropoulos E, Czech M, and Schuster T. inventors; WO  2007,054,556.  ; Chem. Abstr. 2007, 146, 521825
• 3 Wrasidlo W, Doukas J, Royston I, Noronha G, Hood JD, Dneproskaia E, Gong X, Splittgerber U, and Zhao N. inventors; WO  2004,030,635.  ; Chem. Abstr. 2004, 140, 321386
• 4 White LE, Reynolds RC, and Suling W. inventors; WO  2004,005,472.  ; Chem. Abstr. 2004, 140, 105238
• 5 Crowley PJ, Müller U, Dobler M, and Williams J. inventors; WO  2005,123,733.  ; Chem. Abstr. 2005, 144, 88319
• 6a Palanki MSS. Dneprovskaia E. Doukas J. Fine RM. Hood J. Kang X. Lohse D. Martin M. Noronha G. Soll RM. Wrasidlo W. Yee S. Zhu H. J. Med. Chem.  2007,  50:  4279 
• 6b Friedrich K. In Houben-Weyl   4th ed., Vol. E9c:  Schaumann E. Georg Thieme Verlag; Stuttgart: 1998.  p.227 
• 6c Temple C. Rener GA. J. Med. Chem.  1990,  33:  3044 
• 6d Temple C. Rose JD. Elliot RD. Montgomery JA. J. Med. Chem.  1970,  13:  853 
• 6e Israel M. Day AR. J. Org. Chem.  1959,  24:  1455 
• 7a Brzozka L. Baran W. Kraus W. Tomasck P. Polish J. Chem.  1995,  69:  605 
• 7b Deady LW. Grimmet MR. Potts CH. Tetrahedron  1979,  35:  2895 
• 7c Deady LW. Korytsky OL. Rowe JE. Aust. J. Chem.  1982,  35:  2025 
• 7d Wieczorek JS. Talik T. Rocz. Chem.  1962,  36:  967 
• 8 Harris MG. Stewart R. Can. J. Chem.  1977,  55:  380 
• 9a Yang BH. Buchwald SL. J. Organomet. Chem.  1999,  576:  125 
• 9b Prashad M. Hu B. Lu Y. Draper K. Har D. Repic O. Blacklock TJ. J. Org. Chem.  2000,  65:  2612 
• 9c Li H. Wang Y. Yan L. Campbell RM. Anderson BD. Wagner JR. Yingling JM. Bioorg. Med. Chem. Lett.  2004,  14:  3585 
• 10 Wolfe JP. Ahman J. Sadighi JP. Singer RA. Buchwald SL. Tetrahedron Lett.  1997,  38:  6367 
• 11a Graboyes H. Day AR. J. Am. Chem. Soc.  1957,  79:  6421 
• 11b Temple C. Laseter AG. Rose JD. Montgomery JA. J. Heterocycl. Chem.  1970,  7:  1195 
• 12 Cai SX. Huang JC. Espitia SA. Tran M. Ilyin VI. Hawkinson JE. Woodward RM. Weber E. Keana JFW. J. Med. Chem.  1997,  40:  3679 
• 13a Zhao Z. Wisnoski DD. Wolkenberg SE. Leister WH. Wang Y. Lindsley CW. Tetrahedron Lett.  2004,  45:  4873 
• 13b Yeo BR. Hallett AJ. Kariuki BM. Pope SJA. Polyhedron  2010,  29:  1088 
• 14 Scriven EFV. Turnbull K. Chem. Rev.  1988,  88:  297