Synthesis of pyrimidines by direct condensation of amides and nitriles.
A protocol for the single-step synthesis of pyrimidine derivatives by condensation of N-vinyl or N-aryl amides with nitriles is described. Gram-scale synthesis of 4-tert-butyl-2-phenyl-7,8-dihydro-6H-pyrano[3,2-d]pyrimidine serves as a representative procedure for this methodology for azaheterocycle synthesis. This chemistry involves amide activation with trifluoromethanesulfonic anhydride in the presence of 2-chloropyridine and the necessary nitrile. Nucleophilic addition of the nitrile to an activated intermediate followed by annulation affords the pyrimidine product in a single step. The total time necessary for the completion of this procedure is approximately 3 h. This chemistry has been applied to a wide range of amides and nitriles including optically active derivatives.
Movassaghi
Mohammad
M
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. movassag@mit.edu
Hill
Matthew D
MD
D000577:Amides / Q000737:chemistry*; D002625:Chemistry, Organic / Q000379:methods; D009570:Nitriles / Q000737:chemistry*; D011743:Pyrimidines / Q000138:chemical synthesis*
D000577:Amides; D009570:Nitriles; D011743:Pyrimidines