Tetrahydropteridine enzymatic cofactors and inhibitors may be conveniently prepared by reduction of the aromatic precursors with dimethylamine - borane in glacial acetic acid. A short reaction time at 20–60 °C affords tetrahydrofolate analogs in high yield and purity under anhydrous conditions and without protection from air. 3′,5′-Dichloromethotrexate is reduced without hydrogenolysis of chlorine.