Abstract: A methodology to prepare novel 1,6-disubstituted-5,6-dihydropyrrolo-[1,2-f]pteridine derivatives has been developed. The key in this synthesis is a Pictet-Spengler type reaction. The Clauson-Kass reaction of 4,6-dichloro-5-amino-pyrimidine with 2,5-dimethoxyltetrahydrofuran, followed by amination of one of the chloro groups, resulted in 4-amino-6-chloro-5-(1H-pyrrol-1-yl)pyrimidine. Subsequently, 4-amino-6-chloro-5-(1H-pyrrol-1-yl)pyrimidine reacted with an aldehyde or aliphatic ketone in the presence of toluenesulfonic acid in refluxing toluene to yield an imine intermediate, which underwent an intramolecular electrophilic substitution to lead to the corresponding dihydropyrrolo[1,2-f]pteridines in moderate to good yields. The chloro group on the newly formed heterocycle could be readily replaced by a nucleophile, such as an amine. This strategy provides a convenient way to access to a class of heterocyclic compounds with possible interesting biological activities.

Key words: Pyrrolo［1,2-f］pteridine, PictetSpengler reaction, Nucleophilic substitution