Cải tiến quy trình tổng hợp bicalutamide làm thuốc điều trị ung thư tiền liệt tuyến

Bicalutamide ( 1 ), commercially available under the brand name Casodex, is a prostate cancer drug. Bicalutamide is a nonsteroidal anti‐androgenic drug with no endocrine activity. The synthesis methods for bicalutamide have been published by various research groups under the form of articles as well as patents. In this paper, we report an improved procedure for the synthesis of ( R , S )‐bicalutamide ( 1 ) at pilot‐scale starting from 4‐amino‐2‐(trifluoromethyl)benzonitrile ( 3 ) and methacryloyl chloride through 4 steps with overall yield of 66 %; including the amidation of the amine group, epoxidation of the double bond, epoxide ring opening under basic conditions, and selective oxidation of the sulfide group. In the step of the forming intermediate 6 , K 2 CO 3 a cheaper reagent is used instead of NaH. The synthesized bicalutamide meets the USP40 standard with 99.4 % purity. Their structures were determined by MS and NMR spectroscopic methods.