Large-scale synthesis of a pyrrolo[2,3-d]pyrimidine via Dakin-West reaction and Dimroth rearrangement

Pyrrolo[2,3-d]pyrimidines have been widely investigated as pharmaceutically active compounds. In this article, we present a short and efficient synthesis of 4-(3-chlorophenylamino)-5,6-dimethyl-7H-pyrrolo[2,3-d]pyrimidine starting from cheap alanine and malononitrile. To the best of our knowledge, the first application of a Dakin-West reaction on plant scale is demonstrated by elaboration of a modified procedure avoiding uncontrolled release of carbon dioxide. Pyrimidine ring formation is achieved in a simple one-pot reaction which is followed by an equally simple isomerization. The whole synthesis requires neither chromatographies nor extractions, no waste treatment and no special equipment, resulting in a remarkably ecological as well as economical process.