4//-Pyrazolo isoxazole

Cyclopent-2-en-l-one, 2-hydroxy-3-methyl-synthesis, 3, 693 Cyclopentenone, 4-methoxy-formation, 1, 423 Cyclopenthiazide as diuretic, 1, 174 Cyclopent[2,3-d]isoxazol-4-one structure, 6, 975 Cyclophane conformation, 2, 115 photoelectron spectroscopy, 2, 140 [2,2]Cyclophane conformation, 2, 115 Cyclophanes nomenclature, 1, 27 Cyclophosphamide as pharmaceutical, 1, 157 reviews, 1, 496 Cyclopiloselloidin synthesis, 3, 743 Cyclopolymerization heterocycle-forming, 1, 292-293 6H-Cyclopropa[5a,6a]pyrazolo[l,5-a]pyrimidine pyrazoles from, 5, 285 Cydopropabenzopyran synthesis, 3, 700 Cyclopropachromenes synthesis, 3, 671 Cyclopropa[c]dnnolines synthesis, 7, 597 Cyclopropanation by carbenes... 

Pyrazolone-1,2-dioxides 311 were subjected to cycloaddition with a wide range of olefinic compounds leading to the 0-2,3,3 ,4-tetrahydro-pyrazolo[l,5-3]isoxazole cycloadducts 312. The behavior of these reactive species 311 toward unsaturated compounds, stereochemical and mechanistic aspects, were discussed in details (Equation 134) <1994J(P2)1337>. 

A series of pyrazolo[3,4-, pyridazinones 430 and analogues, potentially useful as peripheral vasodilators, were synthesized and evaluated as inhibitors of PDE5 extracted from human platelets. Several of them showed ICso values in the range 0.14-1.4 pM. A good activity and selectivity profile versus PDE6 was found for compound 430 (6-benzyl-3-methyl-l-isopropyl-4-phenylpyrazolo[3,4-r/]pyridazin-7(6/7)-one). Structure-activity relationship studies demonstrated the essential role played by the benzyl group at position 6 of the pyrazolopyridazine system. Other types of pyridazinones fused with five- and six-membered heterocycles (pyrrole, isoxazole, pyridine, and dihydropyridine), as well as some open-chain models were prepared and evaluated. Besides the pyrazole, the best of the fused systems proved to be isoxazole and pyridine <2002MI227>. 

Pyrazolo[l,5-a]pyrimidines are obtained via catalytic hydrogenation of the pyrazolylisoxazoles 88 with W2/Raney nickel. The reagent caused isoxazole ring opening to give the intermediate aminopyrazole derivatives,... 

More recently, Jin (92MI2) investigated several mono- and dimethylated cycloheptazol-8-ones. The similarity of the electronic spectra of pyrazolo-tropones 85, 86a, and 87a is explained by the very similar 10-77 systems present. However, the spectra of isoxazoles 90 and 91 and of oxazole 114b are different from those of the pyrazoles. This difference was attributed to the small contribution of the oxygen-atom lone-pair electrons to the conjugation, which minimizes the contribution of the 10-77 system. 

In an interesting reaction, the oxazolo[3,4-6]pyridine (598) was converted to the pyrazolo[3,4-6]pyridine (599) (70%) by heating at reflux in a mixture of aniline, ammonium acetate, and glacial acetic acid for 2 h <9lPS(63)ll9>. The authors propose that the reaction proceeds by ring opening of the isoxazole ring by aniline with the formation of a phenylhydrazino intermediate which then cyclizes (Equation (61)). 

Pyrazolo[2,3-a]imidazole possesses sedative and antipyretic action. Imidazo[2,l-fc]-[l,3,4]thiadiazoles are antithrombotic and thrombolytic agents. Furo[3,2-c]isoxazol-5-ones and their enantiomeric or racemic mixtures are used in the production of antitumor agents obtained from methyl-L-acosaminide and -daunosaminide. 

Intermediate 12, on heating in benzene, gives the isoxazole 13, whereas related compounds give, for example, pyrazolo[l,5-a] pyridines.33 Irradiation of the 6>nitrocholest-5-enes 14 in acetic acid at reflux gave the steroidal isoxazoles 15. It was proposed that the isoxazoles were formed via the labile intermediate 16, which was formed by hydrogen abstraction as shown in Scheme 1. The possible importance of this method for functionalizing a nonactivated carbon atom was pointed out.34 We are unaware of examples involving CCNOC and CNOCC synthons. 

Pyrazolo[l,5-i]isoxazoles were prepared by cycloaddition of pyrazolone jV,iV-dioxides with electron-rich alkenes <94JCS(P2)1337>. In general, mixtures of diastereomeric regioisomers are obtained, with the predominant formation of exo cycloadducts. The l-methyl-2-aminoindazolium salt (164) reacted with acetylacetone in the presence of triethylamine to give the pyrazolo[2,3-Z)]indazole derivative (76), which was oxidized with lead tetraacetate to give (77) (Section 8.04.6.1) <76CPB2267>. 

A-phenylmaleimide/ ° The complex nitrile oxide (736), prepared from dichloroglyoxime (HON=CCl—CC1=N0H) and dipropargylamine, forms the intramolecular cyclo-adduct 137) 3,6-Diphenylpyridazine 1,2-dioxide (738) rearranges photochemically to the isoxazolo-isoxazole (739), which is also produced by the oxidation of the dioxime HON=CPhCH=CHCPh=NOH. Regiospecific cycloaddition of benzonitrile oxide to the pyrazoline (740) affords the pyrazolo-oxadiazole (741)/ ... 

Cycloaddition to 4H-pyrazol-4-one N-oxides Pyrazolo[2,3-b]isoxazol-4-ones... 

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