Symmetrically and Unsymmetrically Bridged Methylenebis(allopurinols): Synthesis of Dimeric Potential Anti-Gout Drugs

摘要

Liquid-liquid phase transfer alkylation of 4-methoxy-pyrazolo[3,4-d]-pyrimidine (>1a) with a dichloromethane/dibromomethane mixture (3:1, v/v) gave the regioisomeric methylenebis(heterocycles) >3a–>5a. These were converted by dilute aqueous sodium hydroxide containing dimethylsulfoxide (DMSO) at concentrations between 0 and 60 vol-% into the methylenebis(allopurinols) >3b–>5b by nucleophilic SNAr reactions at C(4). The effect of DMSO on the reaction kinetics was investigated.