A Green Approach for the Synthesis of 5,6‐Dihydropyrimido[4,5‐<i>d</i>]Pyrimidines From <i>N</i>‐Uracil Amidines in Water

ABSTRACT 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 Cs 2 CO 3 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.