Pyrimidine-2,4,6-trione, 2,5-dimethyl

The Michael addition of 6-aminouracils to dimethyl allene-l,3-dicarboxylate in methanol or dimethyl sulfoxide provides a pentenedioic acid side chain in the 5-position capable of further elaboration (Z-isomer in methanol, -isomer in dimethyl sulfoxide). Heating these adducts of 6-aminouracil or its 1-methyl derivative in dimethylformamide gives the corresponding pyri-do[2,3-d]pyrimidine-2,4,7(l//,3//,8//)-triones 7. 44... 

The acrylic acid ester side chain may also be introduced by the Wittig reaction of 6-chloro-l,3-dimethyl-2,4-dioxo-l,2,3,4-tetrahydropyrimidine-5-carbaldehyde with the appropriate ylide. Subsequent conversion to a 6-amino compound and ring closure in the presence of triethyl-amine gives 8-alkyl-l,3-dimethylpyrido[2,3-t/]pyrimidine-2,4,7(l//,3//,8W)-triones 9. 45 146 Exclusive formation of pyrido[2,3-t/]pyrimidines is achieved by refluxing the acrylic acid esters in a mixture of triethylamine and dimethylformamide in the presence of l,5-diazabicyclo[4.3.0]-non-5-ene (DBN).147 55t... 

The dimethylformamide/phosphoryl chloride reagent has been used to cyclize 6-(acylamino)-uracils by introducing the missing carbon unit.201 Thus, treating l,3-dimethyl-6-[(cyanoacetyl)amino]uracil with dimethylformamide/phosphoryl chloride yields 1,3-dimethyl-5-chloropyrido[2,3-rf]pyrimidine-2,4,7(l//,3f/,8//)-trione (8, R = H). 

It is, however, possible to obtain either pyrido[2,3-rf]pyrimidine-2,4,7(1/7,377,8//)-triones or, to a lesser extent, py rido[2,3-acetic acid 99 affords ethyl 1,3-dimethyl-2,4,7-trioxo-l,2,3,4,7,8-hexahydropyrido[2,3-d]pyrimidine-6-carboxylate. Further examples of this pathway are the reaction of diethyl (ethoxymethylene)malonate with 6-amino-165 or 6-(methylamino)-l,3-dimethyluracil 222 neat at 220-230 °C, or with 6-amino-2-methoxypyrimidin-4(3/7)-one223 in acetic acid to yield the corresponding ethyl 2,4,7-trioxo-l, 2,3,4,7,8-hexahydropyrido[2,3-[Pg.118]

With 6-aminouracil, prop-2-ynal or 3-phenylprop-l-yn-3-one in aqueous alkali at 0°C reacts to furnish pyrido[2,3-phenyl derivative 232 similarly, methyl propiolate and l,3-dimethyl-6-aminouracil (33) in refluxing water give 1,3-dimethylpyrido[2,3-c/]pyrimidine-2,4,7(177,3//,8//)-trione (34).165 In protic media such as water or methanol, irrespective of the N1 substituent, the reaction with 6-aminouracils largely yields methyl 2,4,7-trioxo-l,2,3,4,7,8-hexahydropyrido[2,3-d]pyrimidine-5-carboxylates.I42,165,547,584... 

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