Hydroxymethylation and aminomethylation of 6-mercaptopurine and its derivatives

Article abstract of DOI:10.1002/jhet.5570250406

Labile aminomethyl and hydroxymethyl derivatives of 6-mercaptopurine (I) (6-MP) and S⁶-acyloxymethyl-6-MP hav been converted to stable acetyloxymethyl derivatives by their reaction with acetic anhydride. Analysis of the reaction products and comparison of their ¹H nmr spectra and hplc spectra chromatograms with those of acetyloxymethyl derivatives of known structures suggested 1) that the aminomethyl derivatives of 6-MP were 7-substituted derivatives, 2) that the aminomethyl derivative of S⁶-acetyloxylmethyl-6-MP was a 9-derivative, 3) that the hydroxymethyl derivative of 6-MP was a mixture of 7-substituted and S⁶,3-disbustituted derivatives, and 4) that the hydroxymethyl derivative of S⁶-pivaloyloxymethyl-6-MP was a 9-substituted derivative. In addition, a previously unreported dialkyl derivative of 6-MP VI was isolated from its reaction with aminomethylating agent and characterized. Analyses of the ¹H nmr spectra and hplc chromatograms of the reaction of VI with acetic anhydride suggested that VI was a 1,7-disubstituted derivative.