Selective reduction of the 7-oxo group in pyrido[2,3d]pyrimidine-4,7- diones: A new synthetic approach to 5,10-dideazatetrahydrofolic acid (DDATHF)

A selective reduction of the carbonyl group at C7 with borane in THF is accomplished for 2,4-diamino-7-oxo and 2-amino-4,7-dioxo substituted pyridopyrimidines (7a-c) and (13a-c) respectively, the ester group remaining unaltered in both cases. The synthesis of 21c allows a new synthetic approach to 5,10-dideazatetrahydrofolic acid (DDATHF, 1) because it is a common intermediate in two procedures that afford the aforementioned antifolate.