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Synthesis 2009(14): 2379-2284  
DOI: 10.1055/s-0029-1216854
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Efficient Synthesis of 2-Substituted Pyrido[3,2-d]pyrimidines Involving SNAr and Palladium-Catalyzed Cross-Coupling Reactions

Abdellatif Tikada,b, Sylvain Routier*a, Mohamed Akssirab, Jean-Michel Légerc, Christian Jarryc, Gérald Guillaumeta
a Institut de Chimie Organique et Analytique, Université d’Orléans, UMR CNRS 6005, rue de Chartres, BP 6759, 45067 Orléans Cedex 2, France
Fax: +33(2)38417281; e-Mail: sylvain.routier@univ-orleans.fr;
b Laboratoire de Chimie Bioorganique et Analytique, Université Hassan II-Mohammedia, BP 146, 20650 Mohammedia, Morocco
c EA 2962, Pharmacochimie, Université Victor Segalen Bordeaux II, 33076 Bordeaux, France
Further Information

Publication History

Received 4 February 2009
Publication Date:
02 June 2009 (online)

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Abstract

The efficient and original synthesis of various 2-substituted pyrido[3,2-d]pyrimidines is reported. Starting from 2,4-dichloropyrido[3,2-d]pyrimidine, a regioselective pallado-dehalogenation led to 2-chloropyrido[3,2-d]pyrimidine, which was used in SNAr and palladium-catalyzed cross-coupling reactions in order to afford highly functionalized products in very good yields.

Key words

arylations - amination - palladium

    References

  • 1 Hamby JM. Showalter HDH. Pharmacol. Ther.  1999,  82:  169 
    CrossrefGoogle Scholar
  • 2 Smaill JB. Palmer BD. Rewcastle GW. Denny WA. McNamara DJ. Dobrusin EM. Bridges AJ. Zhou H. Showalter HDH. Winters RT. Leopold WR. Fry DW. Nelson JM. Slintak V. Elliot WL. Roberts BJ. Vincent PW. Patmore SJ. J. Med. Chem.  1999,  42:  1803 
    CrossrefGoogle Scholar
  • 3a Rosowsky A. Chen H. J. Org. Chem.  2001,  66:  7522 
    Google Scholar
  • 3b Gangjee A. Adair O. Queener SF. J. Med. Chem.  1999,  42:  2447 
    Google Scholar
  • 4 Natarajan SR. Wisnoski DD. Singh SB. Stelmach JE. O’Neill EA. Schwartz CD. Thompson CM. Fitzgerald CE. O’Keefe SJ. Kumar S. Hop CECA. Zaller DM. Schmatz DM. Doherty JB. Bioorg. Med. Chem. Lett.  2003,  13:  273 
    CrossrefGoogle Scholar
  • 5a Hayakawa M. Kaizawa H. Moritomo H. Koizumi T. Ohishi T. Okada M. Ohta M. Tsukamoto S.-i. Parker P. Workman P. Waterfield M. Bioorg. Med. Chem.  2006,  14:  6847 
    Google Scholar
  • 5b Rueckle T, Quattropani A, Pomel V, Dorbais J, Covini D, and Bischoff A. inventors; WO  2006024666.  ; Chem. Abstr. 2006, 144, 292753
  • 6a Zhang J. Yang PL. Gray NS. Nature Rev. Cancer  2009,  9:  28 
    Google Scholar
  • 6b Klutchko SR. Zhou H. Winters RT. Tran TP. Bridges AJ. Althaus IW. Amato DM. Elliott WL. Ellis PA. Meade MA. Roberts BJ. Fry DW. Gonzales AJ. Harvey PJ. Nelson JM. Sherwood V. Han H.-K. Pace G. Smaill JB. Denny WA. Hollis Showalter HD. J. Med. Chem.  2006,  49:  1475 
    Google Scholar
  • 7a Matulenko MA. Lee C.-H. Jiang M. Frey RR. Cowart MD. Bayburt EK. DiDomenico S. Gfesser GA. Gomtsyan A. Zheng GZ. McKie JA. Stewart AO. Yu H. Kohlhaas KL. Alexander KM. McGaraughty S. Wismer CT. Mikusa J. Marsh KC. Snyder RD. Diehl MS. Kowaluk EA. Jarvis MF. Bhagwat SS. Bioorg. Med. Chem.  2005,  13:  3705 
    Google Scholar
  • 7b Perner RJ. Lee C.-H. Jiang M. Gu Y.-G. DiDomenico S. Bayburt EK. Alexander KM. Kohlhaas KL. Jarvis MF. Kowaluk EL. Bhagwat SS. Bioorg. Med. Chem. Lett.  2005,  15:  2803 
    Google Scholar
  • 7c Cowart M. Lee C. Bioorg. Med. Chem. Lett.  2001,  11:  83 
    Google Scholar
  • 8 VanderWel SN. Harvey PJ. McNamara DJ. Repine JT. Keller PR. Quin J. Booth RJ. Elliott WL. Dobrusin EM. Fry DW. Toogood PL. J. Med. Chem.  2005,  48:  2371 
    CrossrefGoogle Scholar
  • 9 Tikad A. Routier S. Akssira M. Léger JM. Jarry C. Guillaumet G. Synlett  2006,  1938 
    Article in Thieme ConnectGoogle Scholar
  • 10 Tikad A. Routier S. Akssira M. Léger JM. Jarry C. Guillaumet G. Org. Lett.  2007,  9:  4673 
    CrossrefGoogle Scholar
  • 11 Review: Schröter S. Stock C. Bach T. Tetrahedron  2005,  61:  2245 
    CrossrefGoogle Scholar
  • 13a Ligthart GBWL. Ohkawa H. Sijbesma RP. Meijer EW. J. Org. Chem.  2006,  71:  375 
    Google Scholar
  • 13b G arnier E. Audoux J. Pasquinet E. Suzenet F. Poullain D. Lebret B. Guillaumet G. J. Org. Chem.  2004,  69:  7809 
    Google Scholar
  • 14a North ACT. Phillips DC. Mathews FS. Acta Crystallogr., Sect. A  1968,  24:  351 
    Google Scholar
  • 14b Sheldrick GM. Kröger C. Goddard R. SHELX 86 in Crystallographic Computing 3   Oxford University Press; New York: 1985.  p.175-189  
    Google Scholar
  • 14c Sheldrick GM. SHELX 97, Program for the Refinement of the Crystal Structures   University of Göttingen; Germany: 1997. 
    Google Scholar
12

Crystallographic study: The structure of compound 2 has been established by X-ray crystallography (Figure  [¹] ). Colorless single crystals of 2 were obtained by slow evaporation from MeOH-CHCl3 (20:80). The unit cell dimensions were determined using the least-squares fit from 25 reflections (25˚ < θ < 35˚). Intensities were collected with an Enraf-Nonius CAD-4 diffractometer using the CuKα radiation and a graphite monochromator up to θ = 45˚. The data were collected to relatively low resolution, i.e. no reflections were observed for θ > 45˚ with λCu. The data were corrected for Lorentz and polarization effects and for empirical absorption correction.¹4a The structure was solved by direct methods SHELX 86² and refined using SHELX 97² suite of programs.¹4b,c Crystallographic data for the structure 2 in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication (CCDC 718788): Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; E-mail: deposit@ccdc.cam.ac.uk.