Concise Pyrimido[4,5‐ d ]pyrimidine Synthesis via Direct Annulation of N ‐Uracil Amidines with Benzaldehydes Under Transition Metal Free Conditions

A novel and concise route towards the synthesis of pyrimido[4,5‐ d ]pyrimidines via a direct annulation reaction of N ‐uracil amidines with benzaldehydes under transition metal free conditions has been described. The requisite precursors N ‐uracil amidines are obtained via S N AE reaction on 6‐chlorouracil with amidines. A series of pyrimido[4,5‐ d ]pyrimidines has been synthesized in good to excellent yields by the direct annulation of N ‐uracil amidines with benzaldehydes using Cs 2 CO 3 as base and molecular oxygen as oxidant in t BuOH at 100 0 C. This synthetic protocol has a number of advantages such as‐ operational simplicity, use of green oxidant, avoidance of transition metal catalysts or ligands, and easy accessibility of the starting materials, making it a highly practical approach to access various pyrimido[4,5‐ d ]pyrimidines of biological interest.