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Process for the production of ralfinamide methanesulfonate salts or their r-enantiomers
专利权人:
NEWRON PHARMACEUTICALS S.P.A.
发明人:
GIORDANO CLAUDIO,WALDVOGEL ERWIN
申请号:
NZ60264811
公开号:
NZ602648A
申请日:
2011.04.06
申请国别(地区):
NZ
年份:
2014
代理人:
摘要:
Disclosed herein is a process for the production and/or purification of the salt of compound (S)-5-[4-(2-fluorobenzyloxy)benzylamino]propanamide &ndash ralfinamide as represented by the compound of formula (Ia), or the respective R-enantiomer (I&rsquoa), with methane sulfonic acid in the form of the crystalline anhydrous polymorph identified as form A, exhibiting an X-ray powder diffraction pattern having characteristic peaks as given in the specification characterised in that: the salt is produced or purified by crystallization from a solution in a solvent selected from: water, a mixture of water with acetone or an aliphatic ketone of 4-5 carbon atoms, and acetone, an aliphatic ketone of 4-5 carbon atoms, or a mixture thereof or the solid salt containing an undesired amount of the impurities having genotoxic effect and/or of the residual solvents known as potential precursors thereof, is slurried with a solvent selected from: water, a mixture of water with acetone or an aliphatic ketone of 4-5 carbon atoms, and acetone, an aliphatic ketone of 4-5 carbon atoms or a mixture thereof or the solid salt containing an undesired amount of the impurities having genotoxic effect and/or of the residual solvents known as potential precursors thereof is exposed to air stream having high degree of relative humidity at a temperature and for a time sufficient to allow the removal of the above said impurities having genotoxic effect and/or of the residual solvents known as potential precursors thereof and, when the resulting crystalline form of the so obtained salt is the crystalline hemihydrate pseudopolymorph form identified as form H, exhibiting an X-ray powder diffraction pattern having essentially characteristic peaks as defined within the specification or a mixture thereof with the crystalline anhydrous polymorph form A, said hemihydrate pseudopolymorph form H or the above said mixture thereof is wholly converted into the crystalline anhydrous polymorph form A by removal of t
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