Optimization of The Synthesis Process of New Androgen Receptor Degraders Key Intermediate
YXG-158 is an androgen receptor degrader with a new structure which is expected to solve the clinical drug resistance problem in patients in castration-resistant prostate cancer.The difficulty in scaling up its production lies in the key intermediate(3S,10R,13S)-10,13-dimethyl-17-(4-methyl-1H-imidazol-1-yl)-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthrene-3-o1(6).In this paper,intermediate 6 was synthesized from 17-iodoandrostane-5,16-diene-3-β-ol(7)by one-step Ullmann coupling reaction.The yield was 30.7％,the purity was 99.72％,and the re-gional isomer 8 only accounted for 0.28％of the product.Ullmann coupling reaction can greatly sim-plified the synthesis route,increased the reaction yield,and was conductive to industrial production.
prostate cancercastration-resistant prostate cancerandrogen receptor degraderUllmann coupling reactionsynthesis process optimization
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