New method for synthesis of pyrazolo[1,5-a]pyrimidines from cyanoacetohydrazide and push pull systems

Abstract

Experimental evidence on the powerful biological activity of
pirazolo[1,5-a]pyrimidines] has been supported by several reports in the last
years, which has made possible their wide utilization in the pharmaceutical
industry. For this reason, the synthesis of these condensed heterocycles has
been carried out with increasing interest. The purpose of the work was to develop
a new simpler synthesis method with good yields and purity than those reported
for obtaining similar structures. Therefore the presence of reactive centres in
alquene and dithiethane push pull systems was taken into account making
possible the intramolecular cyclization subsequently to the initial nucleophilic
attack of the cyanoacetahydrazide. The reaction behavior was studied in aloholic
medium as dimethylformamide. In all cases, best results were achieved by using
the aprotic dipolar solvent since it allows the stabilization of the polar transition
states formed through the reaction course. It was demonstrated that the
dithiethanes are less reactive than the keten-S,S-acetals. A reaction scheme is
showed which is agreement with the general reaction mechanism proposed by
Rappaport for the interaction between nucleophiles and push pull ethylenes.
The structures of the most stable intermediate was established on the basis of
the calculations performed by means of the MOPAC 6.0 program. The compounds
synthesized were characterized adequately by means of their elemental
quantitative analysis and several spectroscopic techniques IR, NMR, including
the COLOC method, and the Mass Spectrometry.