Isoxazolo pyrimidines

This type of rearrangement can also occur as a consequence of in situ formation of a suitable intermediate, such as in the case of tandem or cascade reactions. Examples of the isoxazole-to-oxazole rearrangement have been studied both computationally and experimentally, providing evidence of the involvement of a 1,2,4-oxadiazole intermediate (2009JOC351). Synthetically useful cascade rearrangements have also been reported for the one-pot synthesis of indazoles (2011SL3018) and a series of isoxazolo-pyrimidines (2011OL4749). 

Isoxazolo[4,5-d]pyrimidine, 7-bromo-5-chloro-X-ray, 6, 618 <72J8X(2)251) Isoxazolo[4,5-d]pyrimidine, 5,7-dichloro-3-phenyl-UV, 6, 620 <67X675)... 

Isoxazolo[5,4-d]pyrimidine, 4-hydroxy-3-methyl-UV, 6, 620 <64JOC2116) Isoxazolo[5,4-d]pyrimidine, 3-methyl-4-(methylamino)-UV, 6, 620 <64JOC2116) Isoxazolo[5,4-d]pyrimidine, 3-phenyl- H NMR, 6, 619 <77H(7)51) Isoxazolo[3,4-d]pyrimidine-4,6(5//,7W)-dione, 5,7-dimethyl-... 

Intramolecular cycloadditions of 4/f-pyrido[l,2-n]pyrimidin-4-ones 235 (R = H, Me Ph) and MeNHOH HCl gave tetracyclic isoxazolo derivatives 237. In the case of 235 (R = Me) a minor epimer 238 was also isolated (00JCR(S)414). Similar reaction of 235 (R = H, Me, Ph) and sarcosine ethyl ester HCl afforded an isomeric mixture of epimeric tetracyclic pyrrolo derivatives 239 and 240. In the reaction of 235 (R = H) and PhCHjNHCHjCOOEt only one product 241 was obtained. 

Little has been discussed on this topic in CHEC-II <1996CHEC-II(7)431>. The isoxazolo[4,5- / pyrimidin-3,7-diones 185 or 186 are converted into 187 upon oxidation with potassium permanganate in acetone (Scheme 8) <2004BMC265>. 

Thiazolo[5,4-d]pyrimidine l//-Pyrazolo[3,4-b]pyrazine Isoxazolo[4,5-fc]pyrazine... 

The dimethoxy isoxazolo[4,5-pyrimidine derivative (96) showed solvent-dependent photochemistry (Scheme 2). Thus, irradiation in ether followed by alkaline hydrolysis gives compound (98) which is believed to be formed via the intermediate (97). The structure of the product (98) was established by synthesis via reductive cleavage of compound (96) to give the imine (99) and subsequent hydrolysis. Photolysis of compound (96) in carbon tetrachloride afforded a mixture of the products (100)-(102) <85JHC156l>. 

Reaction of azoloazines with oxygen nucleophiles leads, in several cases, to ring cleavage. Cleavage of both the azine and azole rings has been reported. The TV-oxide (158) reacts with 1 N sodium hydroxide to yield the pyrazole derivative (185 R = H) (Equation (19)). Similarly, the reaction of isoxazolo[4,5-d]pyrimidines (186) with benzylamine gives the derivatives (187) (Equation (20)) <76CPB3120>. 

Isoxazolo[3,4-ii]pyrimidines (484) are also obtained via reaction of 6-methylthiouracil-5-car-bonitrile with hydroxylamine <91JHC1039>. In contrast, 6-alkylthio-5-acylpyrimidines react with hydroxylamine to yield products (485), formed via initial condensation at the acyl function <89PHA489). Similarly, the derivatives (486) are produced by the reaction of 3-chloro-5,6-diaryl-pyridazine derivatives with hydroxylamine <89JPR339>. The reaction of compound (487) with hydroxylamine gives the derivative (488) <80BSB65l>. 

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