A versatile, efficient, clean, and facile method was used for the synthesis of pyrano [2,3‐d]pyrimidine derivatives by the one‐pot three‐component condensation reaction of thiobarbituric acid and malononitrile with p‐chlorobenzaldehyde, using Fe3O4 or ZnO or Mn3O4 as nanostructure catalysts. The catalyst could be easily recovered using an external magnet and reused for six cycles with almost a consistent activity. A series of polyheterocyclic compounds containing five and/or six rings fused with each other was designed. The anti‐inflammatory activities for some of the newly synthesized compounds were evaluated. All the synthesized compounds were characterized on the basis of their elemental analyses and spectral data.