Two-step synthetic approach to 6-substituted pyrido[2,3-d]pyrimidine(1H,3H)-2,4-diones from 6-amino-, 6-alkylamino-, and 6-arylamino-1,3-dimethyluracils

The Mannich reaction of 7-aryl-5,6-dihydropyrido[2,3-d]pyrimidines 3, easily accessible by condensation of 6-amino-1,3-dimethyluracil (1) with Mannich bases 2a-c, gives rise to a mixture of 7-aryl-6-(N,N-dimethylaminomethyl)pyrido[2,3-d]pyrimidines 6 and 7 as well as 1,2-bis(7-arylpyrido[2,3-d]pyrimidin-6-yl)ethane 13 the ratio of which depends on the reaction conditions and the amine used. 6-Alkylamino-1,3-dimethyluracils 15-18 were converted to the corresponding 5-(3-oxo-3-phenylpropyl)uracils 19-22 by condensation with the Mannich base 2a. Ring closure of 19-22 was performed by Vilsmeier formylation to afford the 8-alkyl- and 7,8-diaryl-5,8-dihydropyrido[2,3-d]pyrimidine-6-carbaldehydes 9 - 12 via the corresponding iminium salts 27 - 30.