Synthesis of the 7-hydroxy metabolites of methotrexate and 10-ethyl-10-deazaaminopterin

Article abstract of DOI:10.1002/jps.2600760810

The potent folate antagonists methotrexate and 10-ethyl-10-deazaaminopterin are oxidized in vivo to their 7-hydroxy derivatives. A specific cyanation at the C-7 position of the pteridine ring system using diethyl phosphorocyanidate converted the dimethyl esters of methotrexate and 10-ethyl-10-deazaaminopterin to the corresponding 7-cyano dimethyl ester derivatives, which were hydrolyzed to the 7-hydroxy metabolites.