Racemic Resolution of Praziquantel and Praziquanamine

 

RXN 001 - Enantiopure S-(+)-Praziquanamine (S-PZQamine) from MW49-13 is converted to S-(-)-Praziquantel (S-PZQ) (MNR1-1) for biological evaluation.

Starting material from Multigram-scale racemic resolution of praziquanamine with (-)-Dibenzoyl-L-tartaric acid (MW49-13)




Hazard and Risk Assessment:



reaction on 1600
reaction off 0900

To a cooled solution of S-(-)Praziquanamine (MW49-13, S-PZQamine, 2.00 g, 9.89 mmol; M.W. = 202.25 g/mol) in DCM (50 mL) at 0°C was added triethylamine (1.50 g, 2.07 mL, 14.83 mmol, 1.5 eq.; M.W.=101.19 g/mol, density=0.73 g/mL) and cyclohexanecarbonyl chloride (1.59 g, 1.46 mL, 10.88 mmol, 1.1 eq.; M.W.=146.61 g/mol, density=1.10 g/mL). The solution was stirred for 17 h at room temperature.

The solution was quenched with water (10 mL) and stirred for a further 30 min. The layers were separated and the organic layer was washed with saturated sodium carbonate solution (50 mL), 0.5 M HCl (50 mL) and brine (50 mL). Dried over magnesium sulfate, filtered (some product spilt at this stage) and concentrated under reduced pressure. The remaining yellow oil was dried under high vacuum for 4 hours to give a foam which was dissolved in a mixture of acetone/hexane (15 mL, 1:1 mixture) and heated until dissolved. The solution was allowed to stand at room temperature over night and the crystals were filtered off and rinsed with a cold mixture of acetone/hexane.

1st Crop = 0.438 g - very pale yellow crystals

* At this stage it was found the the ee of the starting amine was only 49 % - reaction not taken further.

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