Synthesis of Substituted 1,2,3,4-Tetrahydro-6-methyl-2-oxo-5-pyrimidinecarboxylic Acid Esters: The Biginelli Condensation Revisited

Abstract

m-A general synthesis of substituted 1.2,3,4-tetrahydro-6-methyl-2-oxo-5pyrimidinecarboxylic acid esters from 2-methylene-3-oxobutanoic acid esters and Omethylisourea hydrogen sulfate is reported.The biologically important 1,2,3,4-tetrahydro-6-methyl-2-oxo-5-pyrimidinecarboxylic acid esters (1)' are prepared from an aldehyde, acetoacetic acid ester and urea under strongly acidic conditions (Scheme 1) 2. We have found that this reaction, termed the Biginelli condensation, is not very reliable and often gives low yields 3. Since the reaction is usually carried out in refluxing ethanolic