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7th October 2010 @ 11:14
Acidic cleavage of the N-cyclohexanoyl group of R-(-)-PZQ
- optimized conditions for rac-PZQ: http://www.thesynapticleap.org/node/296

See also:
Hydrolysis of S-(+)-PZQ (MW2-12)

Reaction Scheme MW2-11


Start time: 7:05 PM 05/10/2010
End time: 1:00 PM 06/10/2010

Procedure:
R-(-)-PZQ (300 mg, 960 µmol) was dissolved in EtOH (3 mL) and 1 N HCl (12 mL) was added (cloudy solution) and heated to reflux for 18h. The yellow solution was cooled to room temperature and made basic to pH 12 by adding aq. 5 N NaOH.
- extraction with DCM (3x 5 mL), organic layer was washed with brine, dried over NaSO4, concentrated under reduced pressure

Crude yield of R-(-)-PZQamine: 195 mg (964 µmol, 100%), impurities on the TLC (strong fruity smell - from side products?)

- recrystallisation from toluene (1 mL): 106 mg (524 µmol. 55%) of a pale yellow solid (still fruity odor)
-remain from mother liquor: 67 mg brown-yellow solid

Analytical data:
m.p. 118-119°C (lit.[1] 117-119°).
1H NMR (CDCl3, 200 MHz): d = 1.80 (bs, 1H), 2.71-3.06 (m, 4 H), 3.53 (d, J=17.6, 1H), 3.69 (d, J=17.4, 1H), 3.73 (ddd, J=13.2, 4.7, 1.2, 1H), 4.77-4.91 (m, 2 H), 7.11-7.26 (m, 4H).
Data: 1H NMR MW2-11
[α]D20 = -276° (c=1, DCM) ([α]D20 for R-(-)-PZQamine: -306° (c=?, solvent=?) [2])
C12H14N2O (202.3)
see: http://www.thesynapticleap.org/node/296

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] “Pyrazinoisochinolin-Derivat“, R. Polke, F. Loebich, J. Seubert, H. Thomas and P. Andrews, German Patent Application (1975) DE 2,331,713..
Attached Files
Reaction Scheme MW2-11
1H NMR MW2-11
1H NMR MW2-11 JCAMP-DX