Oxadiazolo pyrimidine 1-oxides

The oxadiazolopyrimidine 1-oxide (164) is attacked by nucleophiles at position 7 of the pyrimidine ring and not, as expected, in the oxadiazolo-ring. Oxidation of the covalent adduct (165), obtained by addition of water, with lead tetra-acetate and then with manganese dioxide yields the dinitro-pyrimidinone (166) (Scheme 81). ... 

SN]-Labeled 4,6-dimethyl-47/-[l,2,5]oxadiazolo[3,4-rf pyrimidine-5,7-dione 1-oxide 290 is conveniently prepared by nitration of commercially available 6-amino-l,3-dimethyl-l//-pyrimidine-2,4-dione using 15N-enriched nitric acid followed by an intramolecular oxidative cyclization with iodosylbenzene diacetate under mild conditions <2000JOC6670>. 

In a similar manner, 47/-[l,2,5]oxadiazolo[3,4- /]pyrimidine-5,7-dione 1-oxides 344 are conveniently prepared in high yields by the oxidative intramolecular cyclization of 6-amino-5-nitro-l/7-pyrimidine-2,4-diones 343 employing iodosylbenzene diacetate as an oxidant in the presence of lithium hydride (Equation 80) <1998JOG6947>. 

Dimethyl-l,2,5-oxadiazolo[3,4-d]pyridazine 1,5,6-trioxide (41) is also an old product [7,11, 31] that has recently been found to react with GSH to give S-nitrosogluta-thione, NO and HNO [32]. It stimulates partially purified rat lung soluble guanylate cyclase, but not the heme-deficient enzyme. The activation is inhibited by ODQ. The product also displays significant vasodilator activity on rat thoracic aorta rings at nanomolar concentrations. Finally, [l,2,5]oxadiazolo[3,4-d]pyrimidine-5,7-dione 1-oxide derivatives (42, R,Ri=CH3,H) release NO, detected as nitrite, in the presence of thiols. A mechanism for this release has been proposed [33]. 

Azine approach. Substituted 6,7,8,8a-tetrahydro-5H-[l,2,4]oxadiazolo[4,5-a]-pyrimidines (613) have been prepared by cycloaddition of nitrile oxides or their chloro-oxime equivalents to a tetrahydro pyrimidine (73GEP2155753). 

Furoxan ring from o-nitrohalides Oxadiazolo [3,4- d] pyrimidine 1-oxides... 

A soln. of 4-amino-6-chloro-5-nitropyrimidine and NaNg refluxed 8 hrs. in tetrahydrofuran 7-amino[1.2.5]oxadiazolo[3,4-d]pyrimidine 1-oxide. Y 81%. 

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