A convenient preparation of tetrahydropteridines and tetrahydrofolate analogs. Synthesis of tetrahydro-3',5'-dichloromethotrexate.

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 degrees 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.