A Green Approach for the Synthesis of 5,6-Dihydropyrimido[4,5-d]Pyrimidines From N-Uracil Amidines in Water

We reported here a straightforward strategy for the synthesis of pharmaceutically important 5,6-dihydropyrimido[4,5-d]pyrimidines through the reaction between N-uracil amidines and functionalized aldehydes under catalyst-free conditions. The condensation reactions between N-uracil amidines and aldehydes proceeded smoothly in water solvent in the presence of Cs₂CO₃ at 100°C for 15 h under nitrogen atmosphere. A range of aromatic aldehydes bearing electron-donating as well as electron-withdrawing groups were well tolerated under optimized reaction conditions and allowed the access of substituted 5,6-dihydropyrimido[4,5-d]pyrimidines in 64%–98% yields. The use of a green solvent, an easy work-up procedure, and a good to excellent yield of products makes this protocol attractive from a sustainable point of view.