1H-1,2,4-Triazole → Letrozole

Participants

Reaction Steps

U.S. Pat. No. 5,473,078 (“the '078 patent”) describes a method of preparing 4-[1-(1,2,4-triazolyl)methyl]benzonitrile by refluxing a solution of α-bromo-4-tolunitrile with 1,2,4-triazole for 15 hours in a mixture of acetonitrile and chloroform. The intermediate is purified by chromatography on silica gel, eluting with chloroform and isopropanol, and then reacted with 4-fluorobenzonitrile and potassium tert-butoxide in DMF, to obtain letrozole. An exemplary process described in the '078 patent is generally depicted in Scheme 1.

Provenance & Evidence