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classificationIPCInventive http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07C231-24
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filingDate 2011-04-06-04:00^^<http://www.w3.org/2001/XMLSchema#date>
inventor http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_a09b2394ccf2d7220909b9d4f09f1661
http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_c73feeab9ffb738005dd5065a799be30
publicationDate 2013-03-06-04:00^^<http://www.w3.org/2001/XMLSchema#date>
publicationNumber EP-2563355-A1
titleOfInvention Process for the production of ralfinamide methanesulfonate salts or their r-enantiomers
abstract The invention relates to a new process for the production and/or purification of the salt of the compound (S)-2-[4-(2-fluorobenzyloxy) benzylamino]propanamide, i.e. ralfinamide, or the respective R-enantiomer, with methanesulfonic acid in high yields and very high enantiomeric and chemical purity in the form of the crystalline anhydrous polymorph identified as form A, wherein said salt is substantially free from impurities having genotoxic effect, such as (C 1 -C 5 )alkanylmethanesulfonates, and residual solvents known as potential precursors thereof, such as (C 1 -C 5 )alkanols or esters thereof with lower alkanoic acids. The process foresees (i) production and/or crystallization of the salt, from water, acetone, an aliphatic ketone of 4-5 carbon atoms or mixtures thereof with water, or (ii) slurring the solid salt with (a) water, (b) a mixture of water with acetone or an aliphatic ketone of 4-5 carbon atoms, (c) acetone, an aliphatic ketone of 4-5 carbon atoms or a mixture thereof, or (iii) exposure of the solid salt to air stream having high degree of relative humidity, and, when the obtained product consists as a whole or in part of crystalline hemihydrate pseudopolymorph form H crystals, converting said product into anhydrous form A crystals by submitting it to water removal. The crystalline hemihydrate pseudopolymorph form H of ralfinamide methanesulfonate, or its R-enantiomer, is a useful intermediate for obtaining the crystalline anhydrous polymorph A free from the above impurities having genotoxic effect and/or residual solvents known as precursors thereof, and exhibits a physicochemical profile conferring significant advantages in the design and development of solid dosage forms, in particular, of modified release formulations.
priorityDate 2010-04-27-04:00^^<http://www.w3.org/2001/XMLSchema#date>
type http://data.epo.org/linked-data/def/patent/Publication

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