Heteroannulation of 2-amino-6-thioxouracil: A new access for the synthesis of fused pyrimidine derivatives

In current work, heteroannulation of 2-amino-6-thioxouracil to new fused pyrimidine scaffolds is described, where pyrimidine 1 undergoes cyclocondensation with pyruvic acid derivative 2 and ninhydrin (6) to furnish thiopyranopyrimidine 5 and thienopyrimidine 8, respectively. Alkylation of aminopyrimidine 1 with benzyl chloride consumed two moles to form S- and N-alkylated product 9. Subjecting compound 9 to aminolysis with aniline derivatives resulted in 4-aminopyrimidine 10a,b through Dimorth rearrangement. Furthermore, the addition of cyclic enamine 10a,b to ninhydrin and benzoyl isothiocyanate produced pyrimidine derivatives 12a,b and 14. Finally, the addition of enamenic carbon of 10a,b to polarized systems 2 or 18 afforded the pyrido[2,3-d]pyrimidines 17 and 21a-d in moderate to good yield.