Synthesis and applications of [1-(15)N]-labeled 4,6-dimethyl-4H-[1,2,5]oxadiazolo[3,4-d]pyrimidine-5,7-dione 1-oxide as a useful tool for mechanistic investigations

J Org Chem. 2000 Oct 6;65(20):6670-5. doi: 10.1021/jo000835s.

Abstract

[1-(15)N]-Labeled 4,6-dimethyl-4H-[1,2,5]oxadiazolo[3,4-d]pyrimidine-5,7-dione 1-oxide (1-(15)N1) was easily prepared by nitration of commercially available 6-amino-1,3-dimethyl-1H-pyrimidine-2,4-dione using 15N-enriched nitric acid followed by an intramolecular oxidative cyclization with iodosylbenzene diacetate under mild conditions. On the basis of the experimental results using 1-(15)N1, the formation of 8-phenyltheophylline (3), the 1,3-dimethylalloxazines (4: n = 0, 1), and 1,3,7,9-tetramethyl-1H,9H-pyrimido[5,4-g]pteridine-2,4,6,8-tetraone++ + (5) in the thermal reaction of the N-oxide 1 with benzylamine, aniline, or piperidine, and the generation of NO or NO-related species in the reaction with N-acetylcysteamine were reasonably explained by considering the initial attack of the employed nucleophiles on the 3a-position of 1.

MeSH terms

  • Aniline Compounds / chemistry
  • Benzylamines / chemistry
  • Cyclic N-Oxides / chemical synthesis*
  • Cyclic N-Oxides / chemistry
  • Cysteamine / chemistry
  • Isotope Labeling
  • Magnetic Resonance Spectroscopy
  • Nitric Oxide / metabolism
  • Nitrogen Isotopes
  • Piperidines / chemistry
  • Pyrimidines / chemical synthesis*
  • Pyrimidinones / chemical synthesis*
  • Pyrimidinones / chemistry

Substances

  • 4,6-dimethyl-4H-(1,2,5)oxadiazolo(3,4-d)pyrimidine-5,7-dione 1-oxide
  • Aniline Compounds
  • Benzylamines
  • Cyclic N-Oxides
  • Nitrogen Isotopes
  • Piperidines
  • Pyrimidines
  • Pyrimidinones
  • Nitric Oxide
  • Cysteamine