212828-83-6Relevant academic research and scientific papers
Development of a manufacturing process for sibenadet hydrochloride, the active ingredient of viozan
Giles, Melvyn E.,Thomson, Colin,Eyley, Stephen C.,Cole, Andrea J.,Goodwin, Christopher J.,Hurved, Paul A.,Morlin, Andrew J. G.,Tornos, James,Atkinson, Stephanie,Just, Cecelia,Dean, Janet C.,Singleton, John T.,Longton, Andrew J.,Woodland, Ian,Teasdale, Andrew,Gregertsen, Bjoern,Else, Howard,Athwal, Mandip S.,Tatterton, Stephen,Knott, Jason M.,Thompson, Nicola,Smith, Stephen J.
, p. 628 - 642 (2013/09/02)
A process for commercial manufacture of the dual D2- β2 receptor agonist sibenadet hydrochloride has been developed. The process relies upon introduction of operationally simple chemistry at the final stages where two key intermediates are reacted to assemble the final molecule, isolated by crystallization. A nine-stage sequence for synthesis of the key amine hydrochloride intermediate was developed, and modifications to the original process are described. Major strategic improvements were made in definition of the final route to the "side chain" precursor molecule, the second key intermediate, hinging around a thiyl radical addition and subsequent high-yielding telescoped processes for synthesis of this highly crystalline benzoate ester. Development of these chemistries is discussed, together with some issues surrounding definition of the final validated commercial processes.
