Synthesis of 2-Arylamino substituted 5,6-dihydropyrido[2,3-d]pyrimidine- 7(8H)-ones from arylguanidines

A practical protocol was developed for the synthesis of 2-Arylamino substituted 4-Amino-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-ones from α,β-unsaturated esters, malononitrile, and an aryl substituted guanidine via the corresponding 3-Aryl-3,4,5,6- tetrahydropyrido[2,3-d] pyrimidin-7(8H)-ones. Such compounds are formed upon treatment of 2-methoxy-6-oxo-1,4,5,6-tetrahydropyridine-3-carbonitriles with an aryl substituted guanidine in 1,4-dioxane and are converted to the desired 4-Aminopyridopyrimidines with NaOMe/MeOH through a Dimroth rearrangement. The overall yields of this three-step protocol are, generally speaking, higher than the multicomponent reaction, previously developed by our group, between an α,β-unsaturated ester, malononitrile, and an aryl substituted guanidine.