Synthesis of novel 2,4-diamino-6-(arylaminomethyl)thieno[2,3-d]pyrimidines as potential antifolates

ynthesis of 2,4-diamino-6-(arylaminomethyl)thieno[2,3-d]pyrimidines as potential lipophilic antifolates has been developed. The synthetic strategy is based on a sequential transformation of readily available ethyl 2-amino-4-chlorothieno[2,3-d]pyrimidine-6-caboxylate to 2,4-diaminothieno[2,3-d]pyrimidine-6-carbaldehyde, which in the reaction with the corresponding anilines in titanium isopropoxide in the presence of sodium borohydride furnished the title compounds.