We have looked at an alternative process to generate the diamine precursor to PZQ, whose resolution is documented. The process involves reduction of the cyano-imine derived from the published reaction of THIQ with peroxide/tungstate/cyanide. Having been able to reduce 1-cyanoisoquinoline very cleanly using Pd/C we anticipated that it would be possible to do the same here. It would be important, however, to maintain acidic conditions to prevent the retro-addition of the cyanide (well documented for the 1-cyano and 1-(nitromethyl)isoquinolines with a free N-H).
Now that both racemic and single enantiomer PZQAmine are available, it is possible to determine phase diagrams - either binary, based on MPt, or ternary based upon solubility. But why do this ?
The PZQ-enamide is shown below. This is an intermediate in the stereoablative route to enantiopure PZQ. HPLC trace for PZQ-enamide (using ChiralcelOD-H, solvents: Hex:IPA:TEA 60:40:0.1, Flow Rate: 0.7 mL/min) gives retention time: 15.772 mins. Original HPLC trace attached below.
(Note comparison HPLC trace for PZQ itself is here.)
