The commercial route to dacomitinib: the first example of mild conditions for a dimroth rearrangement

摘要

This presentation describes the process research and development efforts towards the commercial route to Dacomitinib, a pan-HER inhibitor currently in PIII clinical trials for the treatment of Non-Small-Cell-Lungs-Cancer (NSCLC). In the first part of the talk, several routes to Dacomitinib will be discussed, highlighting how the commercial route was selected. The second part is focussed on the optimization of the Dimroth rearrangement reaction which employs unprecedented mild conditions. The final part of the talk describes in more detail how the final process was established, overcoming processing issues encountered in the initial process.