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28th January 2011 @ 06:40
rac-PZQamine and R-(-)-PZQamine were purified by recrystallisation from toluene for performing a binary phase diagram via DSC by Nick (Almac Sciences)


rac-PZQamine
Synthesis: Hydrolysis of rac-PZQ (MW2-14)
Purification: recrystallized two times from toluene

m.p. = 119.0 - 119.8°C. (colorless to pale orange solid)
Further analytical data: http://www.thesynapticleap.org/node/296
NMR: http://www.thesynapticleap.org/node/294 (see attachment)

R-(-)-PZQamine (97% ee)
Synthesis, see: Multigram-scale racemic resolution of praziquanamine with (-)-Dibenzoyl-L-tartaric acid (MW49-13)
Purification: recrystallized two times from toluene
Quantification of the enantiomeric excess, see: N-Cyclohexanoyl-protection of the enantiopure R-(-)-PZQamine in a multigram scale (MW48-4)

m.p. 121.1 - 122.0°C. (colorless to pale orange solid)
[α]D20 = -305° (c=1, DCM).
1H NMR: Data: 1H NMR MW49-13 (-)-PZQamine.pdf
Chiral HPLC: R-(-)PZQ 98.5% -> 97% ee
Chiralcel OD-H, hexane/iso-propanol/Et3N = 60/40/0.1, 0.7 ml/min flow rate, RT: (R-(-)PZQ): 11.1 min, S-(+)PZQ: 13.6 min. Data: HPLC MW48-4.jpg

Note: PZQamine degenerates slowly at room temperature (turns yellow - orange)

References:
[1] Formation of Pyrazinoisoquinoline Ring System by the Tandem Amidoalkylation and N-Acyliminium Ion Cyclization: An Efficient Synthesis of Praziquantel, J. H. Kim, Y. S. Lee, H. Park and C. S. Rim, Tetrahedron 1998, 54, 7395-7400.(DOI: doi:10.1016/S0040-4020(98)00401-3)

[2] Synthesis of “Trioxaquantel”(R) Derivatives as Potential New Antischistosomal Drugs, S. A.-L. Laurent, J. Boissier, F. Coslédan, H. Gornitzka, A. Robert and B. Meunier, Eur. J. Org. Chem. 2008, 895-913. (DOI: 10.1002/ejoc.200700975)

[3] The Resolution of Praziquantel, M. Woelfle, J.-P. Seerden, J. de Gooijer, K. Pouwer, P. Olliaro and M. H. Todd1, www.openwetware.org, 2011