A method of preparation of 5 amino 3,4 dinitropyrazole (1) from 3(5) methyl 5(3) nitro and 3(5) methyl 4,5(3) dinitropyrazoles was developed, the key step of which was the Hofmann rearrengement of nitro and dinitropyrazolecarboxamides. The protonation of 5 amino 3,4 dinitropyrazole was studied by spectral methods (UV spectroscopy, NMR spectroscopy). In spite of low basicity of the amino group, compound 1 undergoes N arylation, N nitration, and annulation reactions with formation of dinitropyrazolo[5,1 a]pyrimidine derivatives and hitherto unknown dinitroimidazo[1,2 b]pyrazole derivatives. Diazotization of 1 leads to 5 diazo 3,4 dinitropyrazole (19), which exists in the form of the internal salt. Some reactions of this compound were studied and the formation of the corresponding 5 halogeno(azido) 3,4 dinitropyrazoles under the action of the halide and azide ion was shown. Dinitropyrazolo [5,1 c][1,2,4]triazine and 7 hydroxydinitro 4,7 dihydropyrazolo[5,1 c] [1,2,4]triazine deriva tives were obtained by the action of active methylene compounds on the betaine 19.
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.
Fused pyrimidine derivatives R 0515Liquid-Phase Synthesis of Combinatorial Libraries Based on 7-Trifluoromethyl-Substituted Pyrazolo[1,5-a]pyrimidine Scaffold. -More than 2200 carboxamides of type (V), (VI), (IX), and (X) are prepared on a 50-100-mg scale using special CombiSyn synthesizers. Key reactions include assembly of the pyrazolo[1,5-a]pyrimidine ring by condensation of 5-aminopyrazole derivatives with trifluoromethyl-β-diketones. Target carboxamides are obtained from the condensation products by conversion into acid chlorides, treatment of the latter with amines, and for the appropriate cases, selective reduction of the pyrimidine ring by NaBH4. -(DALINGER, I. L.; VATSADSE, I. A.; SHEVELEV, S. A.; IVACHTCHENKO*, A. V.; J. Comb. Chem. 7 (2005) 2, 236-245; Chem. Div. Labs, Inc., San Diego, CA 92121, USA; Eng.) -Klein 32-152
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.