Some nucleophilic substitutions in 2,4-and 2,4,8-trichloro-pyrido [3,2-d] pyrimidines

  • Said M. Boyomi
  • Abdel-Kader M. Ismaiel
  • Hassan M. Eisa
  • Mohmed M. El-Kerdawy
Original Articles
Received:
  • 18 Downloads

Abstract

Reaction of 6-(acetoxymethyl)-2,4-dichloropyrido[3,2-d]pyrimidine (I) with some nucleophiles was investigated. When I reacted with sodium azide afforded 2,4-diazido derivative (II). Treatment of II with sodium hydroxide underwent cyclization of the 2-azido group to tetrazolo, replacement of 4-azido group by hydroxide ion, and hydrolysis of 6-acetoxy moiety to hydroxy methyl derivative (III). While, reaction of I with hydrazine hydrate resulted in the formation of 2,4-dihydrozino-6-hydroxymethyl derivative (IV).

Key words

Reactivity Nucleophilic Replacement Cyclization 
This is a preview of subscription content, log in to check access.

Literature Cited

  1. 1.
    Bayomi, S.M., Brixner, D.I., Eisa, H.M. Broom, A.D., Ueda, T. and Cheng, Y.C.: Probing the thymidylate synthase active site with bisubstrate analog inhibitors.Nucleosides & Nucleotides 7, 103 (1988).CrossRefGoogle Scholar
  2. 2.
    Srinivasan, A., Amarnath, V., Broom, A.D., Zou, F.C. and Cheng, Y.C.: A potent multisubstrate analogue inhibitior of human thymidylate synthetaseJ. Med. Chem.27, 1710 (1984).PubMedCrossRefGoogle Scholar
  3. 3.
    Temple, Jr. C. Kussner, G.L., Rose, J.D., Smithers, D.L., Bennett, L.L., and Montgomery J.A.: New synthesis of: N-[4-[[(2-Amino-4 (3H)-oxopyrido[3,2d] pyrimidin-6-yl)methyl amino]benzoyl]-L-glutamic acid (8-deazafolic acid) and the preparation of some 5,6,7,8,-tetrahydro derivatives.J. Med. Chem. 24, 1254 (1981).PubMedCrossRefGoogle Scholar
  4. 4.
    Srinivasan, A., Broom, A.D.: Pyridopyrimidines. 12-Synthesis of 8-Deaza Analogues of Aminopterin and Folic Acid.J. Org. Chem 46, 1777 (1981).CrossRefGoogle Scholar
  5. 5.
    Hitchings, G.H., Flion, G.B., Falco, F.A., Russell, P.B. and Vanderwerff, H.: Antagonists of Nucleic Acid Derivatives (I).Lactobacillus casei model.Ann. N. Y. Acad. Sci. 52, 1218 (1950).CrossRefGoogle Scholar
  6. 6.
    Eisa, H.M. Bayomi, S.M., Ismaiel, A.M. and El-Derdawy, M.M.: Some nucleophilic substitutions in the 2,4-dimethoxypyrido 3,2-d pyrimidines.Heterocycles 26, 457 (1987).CrossRefGoogle Scholar
  7. 7.
    Robins, R.K. and Hitchings, G.H.: Studies on condensed pyrimidine systems. XII. Synthesis of some 4-and 2,4-substituted pyrido 2,3-d pyrimidines.J. Am. Chem. Soc.,77 2256 (1955).CrossRefGoogle Scholar
  8. 8.
    Srinivasan, A. and Broom, A.D.: Pyridopyrimidines. 10. Nucleophilic substitutions in the pyrido 3,2-d pyrimidine series.,J. Org. Chem.44, 435 (1979).CrossRefGoogle Scholar
  9. 9.
    Benson, F.R., Hartzel, L.W., Otten, E.A.: Azidopyrimidines.J. Am. Chem. Soc. 76, 1858 (1954).CrossRefGoogle Scholar

Copyright information

© The Pharmaceutical Society of Korea 1989

Authors and Affiliations

  • Said M. Boyomi
    • 1
  • Abdel-Kader M. Ismaiel
    • 2
  • Hassan M. Eisa
    • 2
  • Mohmed M. El-Kerdawy
    • 2
  1. 1.Department of Pharmaceutical Chemistry, College of PharmacyKing Saud UniversityRiyadhSaudi Arabia
  2. 2.Department of Medicinal Chemistry, Faculty of PharmacyUniversity of MansouraMansouraEgypt

Personalised recommendations