Studies on the chemical reactivity and the physical properties of allopurinol (pyrazolo[3,4-d]pyrimidin-4-one) and related compounds

Abstract

Pyrazolo [3,4-d]pyrimidines resemble purines by avoiding disubstitution at the peri-positions 1 and 7, but they also resist 1,2-disubstitution in the pyrazole ring. INDO calculations show that 1,2-disubstituted derivatives of allopurinol are the least stable. The anion of allopurinol is present as a mixture of tautomeric forms and yields upon methylation 1,5-, 2,5-, and 2,7-dimethyl derivatives. Alkylation of 4-methylthiopyrazolo[3,4-d]pyrimidine, either as the neutral molecule or as the anion, offers a convenient approach to the synthesis of many mono- and di-methyl derivatives, which serve as precursors for methylated allopurinols.