Regioselective synthesis of pyrido[2,3-d]pyrimidines

The reaction of diethyl ethoxymethylenemalonate ( 1 ) and 6-amino-1,3-dimethyluracil ( 2 ) was determined to be regioselective. Under acidic conditions the product was the previously isolated 7-oxopyrido2,3-d]pyrimidine ( 3 ), while in the presence of one equivalent of base followed by thermal cyclization, the isomeric 5-oxopyrido2,3-d]pyrimidine ( 5 ) is formed.