A new general synthesis of functionally substituted pyrazolo[1,5-a]pyrimidines

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Synthesis of mesoionic 3-aryl(hetaryl)-1,2,3,4-oxatriazol-5-ones b based on N-aryl-and N-hetarylhydrazones of bromonitroformaldehyde

Dehydrobromination of N-arylhydrazones of bromonitroformaldehyde (at 20°C) in the presence of alkali and ammonium salts of strong mineral acids, HNO₃, silica gel, and Al₂O₃ forms mesoionic 3-aryl-1,2,3,4-oxatriazol-5-ones (3-arylazasydnones). The effect of the electronic properties of the aryl substituent on the course of the reaction is evaluated. This evaluation is used to develop a general method for preparing 3-arylazasydnones with various substituents including novel 3-hetarylazasydnone derivatives of pyrazole, 1,2,4-triazole and pyridine. Aromatic electronic effects (I, R, m, p) of the mesionic 1,2,3,4-oxatriazol-5-on-3-yl moiety are determined by¹⁹F NMR. A scheme is proposed for the dehydrobromination of the bromonitroformaldehyde N-arylhydrazones that includes the intermediate N-aryl-C-(nitro) nitrilimines, ArN^––N=C⁺NO₂, with subsequent isomerization of the latter into 3-arylazasydnones.N. D. Zelinskii Institute of Organic Chemistry of the Russian Academy of Sciences, Moscow 117913, RussiaTranslated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 413–424, March, 1999.     

Kinetics of hydrolysis of five-membered <Emphasis Type="Italic">C</Emphasis>-nitroheterocycles: pyrazole,imidazole, 1,2,4-triazole,and isoxazole derivatives

Alkaline hydrolysis of mono-and dinitro derivatives of five-membered heterocycles, viz., pyrazole, imidazole, 1,2,4-triazole, and isoxazole, is accompanied by the elimination of the nitro group in the form of a nitrite anion. The hydrolysis kinetics was studied by the polarographic and photometric methods. The experimentally determined hydrolysis rate constants depend on the nature of the heterocycle. A possible mechanism for hydrolytic transformations of the compounds under study was proposed on the basis of the calculated thermodynamic parameters of the reaction (Δ G ^≠, ΔH ^≠, ΔS ^≠). Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2719–2725, December, 2005.     

Nitropyrazoles 16. The use of methoxymethyl group as a protecting group for the synthesis of 4-methyl-3-nitro-5-R-pyrazoles

4-Methyl-3,5-dinitropyrazole prepared by nitration of 1,4-dimethylpyrazole readily reacts with methoxymethyl chloride and methyl vinyl ketone in acetonitrile in the presence of a base giving 1-methoxymethyl-4-methyl-3,5-dinitropyrazole and 4-methyl-3,5-dinitro-1-(3-oxobutyl)pyrazole, respectively. The action of the thioglycolanilide anion on 4-methyl-3,5-dinitro-1-(3-oxobutyl)pyrazole results only in the removal of 1-protecting group and the formation of 2-[(3-oxobutyl)thio]acetanilide, while the action of anionic S-nucleophiles on 1-methoxymethyl-4-methyl-3,5-dinitropyrazole leads to the substitution products of the 5-NO₂ group in which the methoxymethyl group can be removed by acid hydrolysis.     

Liquid-phase synthesis of combinatorial libraries based on 7-trifluoromethyl-substituted pyrazolo[1,5-a]pyrimidine scaffold

The parallel solution-phase synthesis of more than 2200 7-trifluoromethyl-substituted pyrazolo[1,5-a]pyrimidine and 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine carboxamides on a 50-100-mg scale has been accomplished. Key reactions include assembly of the pyrazolo[1,5-a]pyrimidine ring by condensation of 5-aminopyrazole derivatives with the corresponding trifluoromethyl-beta-diketones. The libraries from libraries were then obtained in good yields and purities using solution-phase acylation and reduction methodologies. Simple manual techniques for parallel reactions using special CombiSyn synthesizers were coupled with easy purification procedures (crystallization from the reaction mixtures) to give high-purity final products. The scope and limitations of the developed approach are discussed.     

Synthesis and cytotoxicity of 28-carboxymethoxy lupane triterpenoids.Preference of 28-O-acylation over 28-O-alkylation of betulm by ethyl bromoacetate

28-Carboxymethoxy lupane tritepenoids 3 and 4 were synthesized by alkylation of betulin with the THP protected 2- hydroxyethyl iodide followed by oxidation and reduction.Direct reaction of betulin(5) or betulone(10) with ethyl bromoacetate led to 28-O-acylation,instead of 28-O-alkylation.The targeted compounds 3 and 4 were not cytotoxic at the highest concentration tested(75μmol/L),suggesting that elongation of the chain length at the 28-position in both betulinic acid(1) and betulonic acid(2) was detrim...     

Nitropyrazoles 14. Synthesis of 1,3,4-trinitropyrazole and its behavior in the nucleophilic substitution reactions. General method of synthesis of 5-substituted 3,4-dinitropyrazoles

For the first time pyrazole containing three nitro groups in the pyrazole cycle, viz., 1,3,4-tri-nitropyrazole, was obtained by N-nitration of 3,4-dinitropyrazole. 1,3,4-Trinitropyrazole enters the cine-substitution reaction of N-nitro group under the action of 0-, N-, and C-nucleophyls under mild conditions. Thus, general method of synthesis of 5-substituted 3,4-dinitropyrazoles containing free NH fragment was worked out.     

Conjugates of Bispidine and Monoterpenoids as Ligands of Metal Complex Catalysts for the Henry Reaction

Russian Journal of Organic Chemistry - A number of chiral chelating conjugates combining a bispidine central backbone and one or two pinene side fragments were synthesized. It was shown for the...