Synthesis Development of the selective estrogen receptor degrader (SERD) LSZ102

The development of the synthesis of the selective estrogen receptor degrader (SERD) drug candidate LSZ102 from the research synthesis to late phase development synthesis is described in this article. The synthesis of LSZ102 could be significantly improved in regards of overall yield, removal of all chromatographic purifications and number of steps by modifying the original disconnection strategy from a Pd catalyzed Suzuki coupling to a Pd catalyzed conversion of an aryl bromide to a phenol and a Pd catalyzed C-H activation as key step.