Synthesis of 7‐aza‐5,8,10‐trideazafolic acid and its 4‐amino‐derivative as potential antifolates

o‐Aminoamide 8 , an intermediate in our multistep synthesisof the title compounds was prepared from 1,3‐diketone 3 . The following condensation of 8 with chloroformamidine‐HCl ( 9 ) gave pyrido3,4‐d]pyrimidine 10 . Dehydratisation of amide 8 led to o‐aminonitrile 15 , which was cyclocondensated with guanidine ( 16 ) to yield pyrido3,4‐d]pyrimidine‐2,4‐diamine 17 . Coupling of the acids 11 and 18 with diethyl L‐glutamate ( 12 ) and following saponification provided 7‐aza‐5,8,10‐trideazafolic acid 14 and its 4‐amino‐derivative 20 .