A New Multi-Component Synthetic Route to Hexahydropyrido[2,3- d]pyrimidine Derivatives

Pyrido[2,3-d]pyrimidine and some of its derivatives are an important class of heterocyclic compounds displaying diverse range of biological activities including antiviral, antifolate, antimicrobial, antitumor, antifungal, anti-inflammatory, anticonvulsive, antipyretic, anti-proliferative CDK2 and antihistaminic activity [1]. The synthesis of various pyridopyrimidines in view of their structural relation to pteridine has attracted the interest of numerous researchers. But the commen synthetic routes to these bicyclic compounds are limited and mainly involve either construction of pyrimidine ring onto pyridine derivatives or pyridine ring onto pyrimidine core. Both routes require the initial synthesis of the decent precursors before construction of the second ring to obtain the desired products [2]. In this work we wish to report a new, simple, convenient and highly efficient one-pot multi-component route for the synthesis of new hexahydropyrido[2,3-d]pyrimidine derivatives from malononitrile and benzaldehyde through manipulation of their molar ratios. The reaction presumably proceeds by a sequence of Knoevenagel condensation, Michael addition and ANRORC process. The generality of the reaction was surveyed by applying the one-pot multi component reaction (MCR) to a number of substituted benzaldehydes. The aromatic aldehydes with electron-withdrawing groups as substrates reacted very well at faster rate with shorter reaction time in comparison to aromatic aldehydes with electron-donating groups. The structuralassignments of all the newly synthesized compounds 3a-h was based upon spectroscopic and micro-analytical data and 2D-NOESY spectrum, as well.