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Procedure for the production of methanesulfonate salts of ralfinamide or its R enantiomers
专利权人:
Newron Pharmaceuticals S.p.A.
发明人:
GIORDANO, Claudio,WALDVOGEL, Erwin
申请号:
ES11714958
公开号:
ES2590128T3
申请日:
2011.04.06
申请国别(地区):
ES
年份:
2016
代理人:
摘要:
Process for the production and / or purification of the salt of compound (S) -2- [4- (2- fluorobenzyloxy) benzylamino] propanamide ralfinamide (Ia), ** Formula ** ralfinamide (Ia) or the respective R enantiomer (I'a), with methanesulfonic acid in the form of the crystalline anhydrous polymorph identified as form A, which has an X-ray powder diffraction pattern (PXRD) that has essentially characteristic peaks expressed in grades 2q a: 6.93; 7.80; 9.66; 11.38; 12.04; 13.02; 13.82; 15.60; 16.36; 16.62; 17.52; 17.83; 18.75; 19.35; 19.70; 20.34; 20.69; 21.20; 22.69; 22.95; 23.23; 23.50; 24.80; 25.24; 25.8056; 26.01; 27.84; 28.07; 28.55; 29.16; 29.82; 30.77; 31.50; 31.95; 32.38; 33.37; 33.96; 34.61; 34.95; 36.02; 36.46; 37.38; 38.04; 39.66, in which the content of each of the impurities having a genotoxic effect, consisting of one or more (C1-C5) alkyl methanesulfonate (s), is less than 0.05 ppm, and of each one of the residual solvents known as potential precursors thereof, which consist of one or more alkanol (s) (C1-C5) or ester (s) thereof with lower alkanoic acid (s), it is less than 6 ppm, characterized in that: (i) the salt is produced or purified by crystallization from a solution in a solvent selected from: a) water, b) a mixture of water with acetone or an aliphatic ketone of 4-5 carbon atoms, and c) acetone, an aliphatic ketone of 4-5 carbon atoms, or a mixture thereof; or (ii) the solid salt that contains an unwanted amount of impurities that have a genotoxic effect and / or of the residual solvents known as potential precursors thereof, is suspended with a solvent selected from: (a) water, ( b) a mixture of water with acetone or an aliphatic ketone of 4-5 carbon atoms, and (c) acetone, an aliphatic ketone of 4-5 carbon atoms, or a mixture thereof; or (iii) the solid salt, which contains an unwanted amount of impurities that have a genotoxic effect and / or of the residual solvents known as potential precursors thereof, is exposed to an air stream that has a h
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