| 摘要 |
Process (I) for the crystallisation of Iopamidol ((S)-N,N'-bis(2-hydroxy-1- (hydroxymethyl)ethyl)-5- ((2-hydroxy-1-oxopropyl)amino)- 2,4,6-triiodo-1,3-benzenedicarboxamide) (II) from water to afford a crystalline anhydrous form of pharmacopoeia standard involves: (a) dissolving (II) in deionised water by heating; (b) decolourising the solution with active carbon; (c) concn. of the aq. solution in vacuo at 60[deg]C; (d) seeding the hot solution with anhydrous (II); (e) crystallising at 60[deg]C; (f) filtering the ppte; and (g) drying the wet product in vacuo. The use of a 1-4C alcohol to reduce the residual content of reaction solvents in the crystals is also claimed. The aq. solution in step (a) is pref. satd. i.e. contg. > 78.6 g (II)/ml of solution and the amt. of seed crystals added in step (d) is 1-10% of the crude (II). To reduce the content of reaction solvents esp. dimethylacetamide deriving from the previous synthetic steps, the filtered crystals are washed with pref. EtOH. |
