O n e -p o t S y n t h e s i s o f N o v e l P y r i m i d o [ 4 , 5 -d ] p y r i m i d i n e s a n d P y r i d o [ 2 , 3 -d ] p y r i m i d i n e sAbstract: Electron rich 6-[(dimethylamino)methylene]aminouracil 1, undergoes [4+2] cycloaddition reactions with various electron deficient substrates to give pyrimido [4,5-d]pyrimidines and pyrido [2,3-d]pyrimidines, after elimination of dimethylamine from the (1:1) cycloadducts and oxidative aromatisation. The reaction gives excellent yields when carried out under microwave irradiation under solvent-free conditions. It is well known that pyrimidine systems as purine analogues exhibit a wide range of biological activities. [1][2][3][4] Among them, the pyrimido [4,5-d]primidines and pyrido [2,3-d]pyrimidines are an important class of annulated uracils of biological significance because of their connection with purine pteridine systems. 5 Several patents have been reported for the preparation of these fused heterocycles, derivatives of which are useful as bronchodilators, 6 vasodilators, 2 antiallergic, 6,7 antihypertensive 8 and anticancer 6 agents. Recently pyrimido[4,5-d]pyrimidine analogues of folic acid have been screened for anti tumor activity. 9 These strategies, however, involve multistep synthesis employing two-component reactions. Therefore, with the aim of the preparation of these complex molecules, there has been remarkable interest in the synthetic manipulations of uracils, 10 although the synthetic exploitation of the nucleophilic double bond of uracil is an undeveloped field in view of a great variety of potential products. 11 4-Deazatoxaflavin, a member of the pyrimido[4,5-c]pyridazines, inhibits the growth of Pseudomonus 568 and also binds to herring sperm DNA. 12 A new approach to the synthesis of pyrimido[4,5-d]pyrimidines reported by Wamhoff et al. 13 is the aza-Wittig type reaction of iminophosphoranes of 5-aminouracils with aromatic isocyanates leading to functionalised pyrimido[4,5-d]pyrimidines. Broom et al. 14 synthesised pyrido[2,3-d]pyrimidine from the reaction of DMAD and 6-aminouracil in protic solvent but obtained the uncyclised condensed acetylenic adduct when the reaction was carried out in DMF. Wamhoff's group has reported the preparation of substituted pyrido[2,3-d]pyrimidines from 6-substituted uracil via [4+2] cycloaddition with electon-deficient olefins. 15 The main disadvantages of this method are the limitation to electron deficient olefins and the low yield due to side reactions. Hirota et al. synthesised pyrido[2,3-d]pyrimidines by the palladium-mediated C-C coupling reaction of electron-deficient olefins with uracil 1 in refluxing acetic acid, 16 but they used a stoichiometric amount of Pd(OAc) 2 as a coupling reagent. Our synthetic strategy utilising N-sulfonylimines and coumarins or quinones with 6-[(dimethylamino)-methylene]aminouracil affords an unprecedented one-pot synthesis of novel pyrimido[4,5-d]pyrimidines and pyrido[2,3-d]pyrimidines, respectively in good yields in refluxing DMF/ nitrobenzene in 3-4 hours. In rec...
