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 M. Hecht

Research output: Contribution to journalArticle

13 Scopus citations

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 - Mar 1981
Externally publishedYes

ASJC Scopus subject areas

  • Organic Chemistry

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