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 ( 1 H, 13 C, and 19 F) 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. Graphical abstract 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.