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.
[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.
Sako
M
M
Laboratory of Medicinal Chemistry, Gifu Pharmaceutical University, Japan.
Yaekura
I
I
Oda
S
S
Hirota
K
K
D000814:Aniline Compounds / Q000737:chemistry; D001596:Benzylamines / Q000737:chemistry; D003497:Cyclic N-Oxides / Q000138:chemical synthesis* / Q000737:chemistry; D003543:Cysteamine / Q000737:chemistry; D007553:Isotope Labeling; D009682:Magnetic Resonance Spectroscopy; D009569:Nitric Oxide / Q000378:metabolism; D009587:Nitrogen Isotopes; D010880:Piperidines / Q000737:chemistry; D011743:Pyrimidines / Q000138:chemical synthesis*; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000737:chemistry
C416070:4,6-dimethyl-4H-(1,2,5)oxadiazolo(3,4-d)pyrimidine-5,7-dione 1-oxide; D000814:Aniline Compounds; D001596:Benzylamines; D003497:Cyclic N-Oxides; D009587:Nitrogen Isotopes; D010880:Piperidines; D011743:Pyrimidines; D011744:Pyrimidinones; D009569:Nitric Oxide; D003543:Cysteamine