Racemic Resolution of Praziquantel and Praziquanamine

 

Testing a resolution method for (-)-PZQamine with (+)-di-p-anisoyl-D-tartaric acid following a resolution method for (+)-PZQamine with (-)-di-p-anisoyl-L-tartaric acid developed by Syncom B.V.

See also:
Synthesis of the resolving agent (+)-di-p-anisoyl-D-tartaric acid
Upscale: Diastereomeric salt resolution of praziquanamine with (+)-di-p-anisoyl-D-tartaric acid (MW47-2)
Diastereomeric salt resolution of praziquanamine with (-)-di-p-anisoyl-L-tartaric acid obtainig S-(+)-PZQamine (MW47-3)



Start time: 4:35 PM 25/09/2010
End time: 10:10 AM 27/09/2010

Procedure:
rac-Praziquanamine (101 mg, 500 µmol) and (+)-di-p-anisoyl-D-tartaric acid (214 mg, 0.5 mmol) was dissolved in a mixture of isopropanol (2.0 mL) and water (0.4 mL) by heating. The pale yellow solution was allowed to cool to room temperature and stand for 40 h.
The solution was removed with a pipette and the remaining solid was dried in a gentle stream of nitrogen.

Yield: 134 mg (43%) of a colorless amorphous solid
- solid is sparingly soluble in water and MeOH, good soluble in 2 N NaOH
- 11.3 mg used for recrystallisation in MeOH, solid couldn't be completely solved in MeOH (2 mL). Small crystals obtained when mixture cooled to room temperature.

Liberation of the salt with 2 N NaOH, extraction of the aq. layer with DCM (3 x 5 mL), concentrated.
Yield: 25 mg (124 µmol, 25%) PZQamine as a colorless solid
Data: 1H NMR MW47-1 ((-)-PZQamine liberated from the salt)
[a]D20 = -244° (c=1, DCM)

Mother liquor concentrated, solid liberated with 2 N NaOH (see above)
Yield: 30 mg (30%) yellow oil
[a]D20 = +160° (c=1.30, DCM)

loss of PZQamine during work-up (hydrolysis of the compound by NaOH?)