Study on the chemical reactivity of a cyano group in the 5-position of 4 and/or 6-substituted pyrrolopyrimidine nucleosides

The reactivity of the cyano group at the 5-position of the pyrrolopyrimidine nucleosides has been studied with various groups in the 4- and/or 6-positions. The susceptibility of the cyano group toward nucleophilic substitution under basic conditions as influenced by amino groups was found to be in the order: no amino group at positions 4 or 6>4-amino>6-amino>4,6-diamino. The decreased reactivity of the amino substituted derivatives is due to electron release by the amino groups. During the investigation of the reaction of 4-chloro-5-cyano-7-(B-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine with methyl hydrazine, a new tricyclic nucleoside, 6-amino-4-methyl-8-(B-D-ribofuranosyl)(4H ,8H)-pyrrolo[4,3,2-de]pyrimido[4,5-c]pyridazine, was synthesized. Subsequent studies showed that the intermediate was 5-cyano-4-N-l-methylhydrazino-7-(3-D-riboguranosyl)pyrrolo[2,3-d]pyrimidine and cyclized in situ to the tricyclic derivative.