Chemistry of 2-Substituted Pyrimidines. Studies Directed toward the Synthesis of the Pyrimidine Moiety of Bleomycin

William K. Hagmann, Fatima Z. Basha, Mitsunori Hashimoto, R. Bruce Frye, Shosuke Kojo, Sidney Hecht

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Synthetic approaches to 2-substituted pyrimidines have been studied in an effort to facilitate the preparation of the pyrimidine moiety of bleomycin (2). Ethyl 2,5-dimethyl-4-oxopyrimidine-6-carboxylate (4) has been utilized as starting material; its conversion to the respective ethyl 2-(carboalkoxy)-5-methyl-4-oxopyrimidine-6-carboxylates provided electrophilic intermediates for attempted elaboration of the 2-substituent, while treatment of 4 with pyridine promoted the nucleophilic addition of the C-2 methyl group to chloral. Introduction of the requisite β-aminoalaninamide substituent was attempted in several ways, including conjugate addition reactions, the use of imine or enamine intermediates, and via nucleophilic halide displacement. Of particular interest were the use of 4-azidopyrimidines as synthetic intermediates leading to the required 4-aminopyrimidines and the solvent- dependent rearrangement of ethyl 3-azido-3-[4-azido-6-(carboethoxy)-5-methylpyrimidin-2-yl]propionate (46) to ethyl 3-amino-3-[4-azido-6-(carboethoxy)-5-methylpyrimidin-2-yl]acrylate (47) at ambient temperature.

Original languageEnglish (US)
Pages (from-to)1413-1423
Number of pages11
JournalJournal of Organic Chemistry
Volume46
Issue number7
DOIs
StatePublished - 1981
Externally publishedYes

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Pyrimidines
Addition reactions
Imines
Bleomycin
Propionates
Temperature
4-aminopyrimidine
pyrimidine
acrylic acid
azidopyrimidine
pyridine
trichloroacetaldehyde

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Chemistry of 2-Substituted Pyrimidines. Studies Directed toward the Synthesis of the Pyrimidine Moiety of Bleomycin. / Hagmann, William K.; Basha, Fatima Z.; Hashimoto, Mitsunori; Bruce Frye, R.; Kojo, Shosuke; Hecht, Sidney.

In: Journal of Organic Chemistry, Vol. 46, No. 7, 1981, p. 1413-1423.

Research output: Contribution to journalArticle

Hagmann, William K. ; Basha, Fatima Z. ; Hashimoto, Mitsunori ; Bruce Frye, R. ; Kojo, Shosuke ; Hecht, Sidney. / Chemistry of 2-Substituted Pyrimidines. Studies Directed toward the Synthesis of the Pyrimidine Moiety of Bleomycin. In: Journal of Organic Chemistry. 1981 ; Vol. 46, No. 7. pp. 1413-1423.
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