Multicomponent regioselective synthesis of 7-aryl-5-methyl- and 5-aryl-7-trifluoromethyl-2-amino-3-(4′-arylazo)-pyrazolo[1,5-a]pyrimidines and their cytotoxic evaluation.

The present study deals with a highly efficient and regioselective synthesis of 7-aryl-5-methyl- and 5-aryl-7-trifluoromethyl-2-amino-3-(4′-arylazo)-pyrazolo[1,5-a]pyrimidines via multicomponent reaction of hydrazine hydrate, 2-(arylhydrazono)malononitrile and β-diketones in presence of p-toluenesulphonic acid under solvent-free condition. The structure of the isolated products was established on the basis of NMR (1H, 13C, and 19F) and IR spectral data. The scope of the reaction was studied using various β-diketones viz., aliphatic, aromatic, heteroaromatic, and trifluoromethyl-β-diketones. The protocol has several advantages, such as mild conditions, atom economy, practical simplicity, shorter reaction times, and avoidance of multi-step procedures. Seventeen diversely substituted pyrazolo[1,5-a]pyrimidines were screened against two breast cancer cell lines, named MCF-7 and BT474, and two leukemia cell lines, named NALM-6 and SB-ALL, using the MTT cytotoxicity assay. Preliminary results reveal that compound 2-amino-5-(4-bromophenyl)-3-(4-methoxyphenylazo)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine was identified as the most effective compound against all the four cancer cell lines with 65-49% cell survival. An efficient regioselective synthesis of 7-aryl-5-methyl- and 5-aryl-7-trifluoromethyl-2-amino-3-(4′-arylazo)-pyrazolo[1,5-a]pyrimidines is developed using solvent-free sequential multicomponent reaction of hydrazine hydrate, 2-(arylhydrazono)malononitrile with unsymmetrical β-diketones. [ABSTRACT FROM AUTHOR]