Dihydropyrido[2,3-d]pyrimidines by Double [5+1] Annulation

Significance

The synthesis of highly functionalized dihydropyrido[2,3-d]pyrimidines via a double [5+1] annulation strategy is presented. The first step consists of a double Michael reaction of the α-alkenoyl-α-carbamoyl ketene-thioacetals with NH₃. Although the scope of the reaction was not broadly tested, the given reactions proceed in good to excellent yields. In the second step, Vilsmeyer reaction of the derived dihydro-4-pyridones leads not only to ring closure but also to N- and C-formylation to form the highly functionalized 7,8-dihydropyrido[2,3-d]pyrimidin-4(3H)-ones (for R¹ = Ar) and 7,8-dihydropyrido[2,3-d]pyrimidines (for R¹ = H).