Synthesis of New Pyrazolo [5, 1-c] [1, 2, 4] triazines from 5-Aminopyrazole and Study Biological Activity and Cytotoxicity

Abstract

Treatment of 2-[bis(methylthio)methylene]malononitrile 1 with p -Chloroaniline afforded 2-[(4-chlorophenylamino) (methylthio) methylene] malononitrile 2a, of which upon reaction with hydrazine hydrate yielded 5-amino-3-(4-chlorophenylamino)-1 H -pyrazole-4-carbonitrile 3. This compound was utilized as a key intermediate for the synthesis of pyrazolo [5, 1-c] [1, 2, 4] triazines by diazotization of 3 with nitrous acid at low temperature afforded 3-(4-chlorophenylamino)-1 H -pyrazole-4-carbonitrile-5-diazonium chloride 3', in which coupling with active methylene of acetylacetone and malononitrile in the presence of pyridine gave the hydrazone derivatives, which cyclized directly upon addition of acetic acid to produce respective pyrazolo [5, 1- c ] [1, 2, 4] triazine derivatives 7 and 8. Finally, treatment of 3 with acetic anhydride gave the acetyl amide derivative 9. The antibacterial and antifungal activities, as well cytotoxicity against Breast cancer cells (MCF7) of some selected compounds are also reported.