Racemic synthesis of rac-PZQ via the Reissert route

29 Jan
Published by Michael Wolfle

 
The first large scale synthesis of rac-PZQ was developed by the Merck KG and Bayer AG (Merck process).[1,2]  Isoquinoline as a cheap starting material was transformed by the Reissert reaction with cyanide and cyclohexanoyl chloride 2 to the cyano amide 3.
 

 
In the literature to this reaction only a few patent procedures are known, which are not very detailed in description.[3]  To understand the Reissert reaction we start a screening approach under various conditions.

[1]     “Synthesis and properties of praziquantel, a novel broad spectrum spectrum anthelmintic with excellent activity against Schistosomes and Cestodes” J. Seubert, R. Pohlke, F. Loebich, Experientia 1977, 33, 1036-1037.
[2]       History of Praziquantel: http://www.stanford.edu/group/parasites/ParaSites2006/Praziquantel/history.html
[3]    J. Zhongliang, Chinese Patent Application CN101445507