Unforeseen alkylating effect of triethylorthoformate in the synthesis of pyrazolotriazolopyrimidine derivative

The final ring closure reaction of 2-phenylamino-3-aminopyrazolo[3,4-d]pyrimidin-4-ones with triethylorthoformate in the synthesis of 1H-pyrazolo[3,4-d][1,2,4]-8H-triazolo[2,3-a]-4H-pyrimidin-4-one derivatives, unexpectedly gave both the desired product and its N2-ethyl analog. The structure of the latter, which arises from an unexpected alkylating effect of triethylorthoformate, was determined through a combined instrumental mass spectroscopy/NMR study reported elsewhere (S Pucci et al, manuscript in preparation). It was further defined using a comparison between a sample of 4 obtained by synthesis and a sample of 4 isolated by PLC or RP-PLC of the crude reaction product.