The maximum effect of daily doses of dutasteride on the reduction of DHT is dose dependent and is observed within 1 to 2 weeks. After 1 and 2 weeks of daily dosing with dutasteride mg, median serum DHT concentrations were reduced by 85% and 90%, respectively. In patients with BPH treated with dutasteride mg/day for 4 years, the median decrease in serum DHT was 94% at 1 year, 93% at 2 years, and 95% at both 3 and 4 years. The median increase in serum testosterone was 19% at both 1 and 2 years, 26% at 3 years, and 22% at 4 years, but the mean and median levels remained within the physiologic range.
Formula (1) compounds then are dissolved in a suitable organic solvent, preferably THF, and cooled to -20° C. to 0° C., and a fluorinating agent such as hydrogen fluoride, or, preferably, pyridinium poly(hydrogen fluoride) is added to yield formula (m) compounds in which X is fluoro. Formula (m) compounds are dissolved in a suitable organic solvent such as THF followed by addition to a solution of a metalloamide base such as lithium diisopropylamide or, preferably lithium bis(trimethylsilyl)amide in a suitable organic solvent such as THF. To this reaction mixture then is added a triflating agent such s trifluoromethanesulfonic anhydride, or, preferably, N-phenyltrifluoromethanesulfonimide to yield formula (o) compounds.