STUDIES ON THE CHEMICAL-REACTIVITY AND THE PHYSICAL-PROPERTIES OF ALLOPURINOL (PYRAZOLO[3,4-D]PYRIMIDIN-4-ONE) AND RELATED COMPOUNDS

Pyrazolo[3,4-d]pyrimidines resemble purines by avoiding disubstitution at the peri-positions 1 and 7, but they resist 1,2-disubstituion in the pyrazole ring. INDO [intermediate neglect of differential overlap (molecular orbital calculations)] 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-methylhiopyrazolo[3,4-d]pyrimidine, 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.