1428581-10-5Relevant academic research and scientific papers
Development of synthetic routes, via a tropinone intermediate, to a long-acting muscarinic antagonist for the treatment of respiratory disease
Bream, Robert N.,Hayes, Doug,Hulcoop, David G.,Whiteman, Alexandra J.
, p. 641 - 650 (2013/06/27)
This contribution describes the development of two synthetic routes to an investigational muscarinic antagonist for the treatment of chronic obstructive pulmonary disease. The first route used a starting material which was in plentiful supply within the GSK network and was used to make material for early clinical trials and safety assessment studies. Further investigations identified a second, potential long-term manufacturing route from commercially available building blocks, using substrate control to install the two stereocentres with excellent selectivity. A key step was a substrate-directed epoxide reduction which also gave rise to a minor byproduct through a skeletal rearrangement of the tropane ring. A deuterium-labeling experiment was carried out, which shed light on the origin of the byproduct, and also guided the improvement of reaction conditions.
