Protocol abstract
Nature Protocols 2, - 2018 - 2023 (2007)
Published online: 16 August 2007 | doi:10.1038/nprot.2007.280
Subject Categories: Isolation, purification and separation | Synthetic chemistry | Spectroscopy and structural analysis
Synthesis of pyrimidines by direct condensation of amides and nitriles
Mohammad Movassaghi1 & Matthew D Hill1
Abstract
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.
- Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Correspondence to: Mohammad Movassaghi1 e-mail: movassag@mit.edu
nature-products
A-Z product listing
- 2-ClPyr(Sigma-Aldrich)
- Acetone(Sigma-Aldrich)
- Anhydrous CH2Cl2 (Baker)
- Anhydrous sodium sulfate(EMD Chemicals Inc.)
- Balance(Sartorius)
- CH2Cl2 (Sigma-Aldrich)
