Pyrido pyrimidine-2,4-diones uracils

The one-pot MCR of methylene active nitriles 47 has been used in the synthesis of both pyrano- and pyrido[2,3-d]pyrimidine-2,4-diones in a single-mode microwave reactor [90]. Microwave irradiation of either barbituric acids 61 or 6-amino- or 6-(hydroxyamino)uracils 62 with triethyl-orthoformate and nitriles 47 (Z = CN, C02Et) with acetic anhydride at 75 °C for 2-8 min gave pyrano- and pyrido[2,3-d]pyrimidines in excellent yield and also provided a direct route to pyrido[2,3-d]pyrimidine N-oxides (Scheme 27). 

A series of pyrido[2,3-rf pyrimidine-2,4-diones bearing substituents at C-5 and/or C-6 were synthesized using palladium-catalyzed coupling of uracil derivative 417 with vinyl substrates or allyl ethers to give the regioisomeric mixtures of 418/419 and 420/421, respectively. The ratio of the isomeric structures was dependent on the substituent R. In the case of the reaction with -butyl vinyl ether, only the product 419 was obtained. However, the reactions with acrylonitrile, ethyl acrylate, 2-trifluoromethylstyrene, and 3-nitrostyrene afforded only 418. Also, reaction with allyl phenyl ether gave only 420. The key intermediate 417 was prepared by the reaction of 6-amino-l-methyluracil with DMF-DMA (DMA = dimethylacetamide), followed by N-benzylation with benzyl chloride and vinyl iodination with iV-iodosuccinimide (NIS) (Scheme 15) <2001BML611>. 

Other typical C3 components are 2-aryl-3-(dimethylamino)acryladehyde.257 3-(methylamino)-bul-3-en-2-one, A-unsubstituted 2-(aminomethylene)cycloalkanones,258 or l-phenyl-3-pipe-ridinoprop-2-en-l-one,259 all of which can be regarded as vinylogous amides. With 4-amino-uracils in dilute acetic acid at reflux temperature, pyrido[2,3-d]pyrimidine-2,4(1 f/,3//)-diones 26 are obtained. According to the position of substituenls in Ihese cases, the amino group of the uracil reacts with the /5-vinyl carbon, followed by cyclization through electrophilic attack of the aldehyde or ketone carbonyl.257,259... 

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