Preparation of aromatase inhibitors. Synthesis of 19,19-difluoro-4-hydroxyandrost-4-ene-3,17-dione and related compounds

Abstract

A new route to 19,19-difluoroandrost-4-ene-3,17-dione (2) has been devised, in which the key step is the reaction of (diethylamino)sulphur trifluoride (DAST) with 3,19-dioxoandrost-4-en-17β-yl benzoate (5). A novel rearrangement product (7) was also produced in this reaction. Compound (2) and its 4-hydroxy derivative (3; R = H) inhibited human placental aromatase in vitro, but were not as potent as 4-hydroxyandrost-4-ene-3,17- dione (1).