Abstract A short and efficient synthesis for 5-substituted-4, 6-dioxo-pyrrolo [2, 3-d] pyrimidines has been developed by the cyclocondensation of α, α-dibromoaldehydes with 2, 4-diamino-6-hydroxypyrimidine under mild basic conditions in good yields. Application of this protocol has been demonstrated in the synthesis of a metabolite of Pemetrexed disodium, a novel multi-targeted antifolate.