An Efficient Three-Component, One-Pot Synthesis of New Pyrimido[4,5-d]pyrimidine-2,4-diones

A new pyrimido [4,5-d]pyrimidine-2,4-(1H,3H,5H,8H)-dione derivatives have been synthesized in good yields in a three-component, one-pot, and efficient process by condensation reaction of 6-amino-1,3-dimethyluracil, aldehyde and 2-benzylisothiourea hydrochloride under solvent-free conditions.The importance of fused pyrimidines, common source for the development of new potential therapeutic agents, 1 is well known.Among them, the pyrimido [4,5-d]pyrimidines and pyrimido [2,3-d]pyrimidines are an important class of annelated uracils with biological significance because of their connection with purine pteridine system. 2 Numerous reports delineate the antitumor, 3 antiviral, 4 antioxidant, 5 antifungal, 6 and hepatoprotective 7 activity of these compounds.Therefore, for the preparation of these complex molecules large efforts have been directed towards the synthetic manipulation of uracils.As result, a number of reports have appeared in literature, which usually requires forcing conditions, long reaction times, and complex synthetic pathway. 8Thus new routes for the synthesis of these molecules have attracted considerable attention in search for a rapid entry to these heterocycles.With the emphasis on the search for atom-efficient transformations of easily available starting materials into complex organic molecules, reactions that provide maximum diversity are especially desirable.Here, multicomponent reactions 9 (MCRs) have emerged as powerful strategy.MCRs are economically and environmentally very advantageous because multi-step syntheses produce considerable amounts of waste mainly due to complex isolation procedures often involving expensive, toxic and hazardous solvents after each step. 9Considering the above reports and in continuation of our previous works on synthesis of heterocyclic compounds, 10 herein, we wish to report an efficient, one-pot, and three-component method for the preparation of 1,3-dimethyl-7-(benzylthio)-5-arylpyrimido [4,5,d]pyrimidine-2,4-(1H,3H,5H,8H)-dione derivatives 4 (Scheme 1).