PROCESS FOR THE PREPARATION OF VORINOSTAT FROM ANILINE, HYDROXYLAMINE AND SUBERIC ACID STARTING MATERIALS

摘要

Disclosed is a process for the preparation of vorinostat (also known as N-hydroxy-N'-phenyl-octanediamide or suberoylanilide hydroxamic acid (SAHA)), comprising: (a) reacting suberic acid with aniline, or a salt thereof, to form suberanilic acid; and (b) reacting the suberanilic acid formed in step (a) with hydroxylamine, or a salt thereof; or (a') reacting suberic acid with hydroxylamine, or a salt thereof, to form N-hydroxy-7-carboxy-heptanamide; and (b) reacting the N-hydroxy-7-carboxy-heptanamide formed in step (a') with aniline, or a salt thereof; wherein step (a) involves a coupling agent selected from 1,3-dicyclohexylcarbodiimide (DCC); 1,1'-carbonyldiimidazole (CDI); 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (WSC.HC1); 1,3-diisopropylcarbodiimide (DIC); or a mixture thereof; and wherein step (b) involves a coupling agent selected from 1,3-dicyclohexylcarbodiimide (DCC); 1,1'-carbonyldiimidazole (CDI); 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (WSC.HCI); 1,3-diisopropylcarbodiimide (DIC); or a mixture thereof.