BARBANTI, Elena,FARAVELLI, Laura,SALVATI, PATRICIA,CANEVOTTI, Renato,PONZINI, Francesco
申请号：
ES08860373
公开号：
ES2655706T3
申请日:
2008.12.01
申请国别(地区):
ES
年份:
2018
代理人:
摘要：
A process for producing a compound of 2- [4- (3- or 2-fluorobenzyloxy) benzylamino] propanamide with a high degree of purity selected from (S) -2- [4- (3-fluorobenzyloxy) benzylamino] propanamide (safinamide ) of formula (Ia), (S) -2- [4- (2-fluorobenzyloxy) benzylamino] propanamide (ralfinamide) of formula (Ib) safinamide (Ia): 3-F ralfinamide (Ib): 2-F the respective enantiomers R (I'a) and (I'b), the respective racemic mixtures (Ia, I'a) and (Ib, I'b) and the salts thereof with pharmaceutically acceptable acids in which safinamide (Ia ), ralfinamide (Ib), the respective R enantiomer (I'a) or (I'b), or the respective racemic mixture (Ia, I'a) and (Ib, I'b) or a salt thereof with a pharmaceutically acceptable acid has a content of the respective impurity, (S) -2- [3- (3-fluorobenzyl) -4- (3- fluorobenzyloxy) -benzylamino] propanamide (IIa), (S) -2- [3 - (2-fluorobenzyl) -4- (2-fluorobenzyloxy) - benzylamino] propanamide (IIb), ** Formula ** the respective R enantiomer (II'a) or (I I'b), or the respective racemic mixture (IIa, II'a) or (IIb, II'b) or a salt thereof with a pharmaceutically acceptable acid, which is less than 0.03%, (by weight) , characterized in that a Schiff base intermediate of formula (IIIa), (IIIb) ** Formula ** the respective R enantiomer (III'a) or (III'b) or the respective racemic mixture (IIIa, III'a) or (IIIb, III'b) (i) is obtained by an iminoalkylation reaction of 4- (3- or 2-fluorobenzyloxy) benzaldehyde with L-alaminamide or Dalaninamide or its racemic mixture, without any addition of molecular sieves, in a solvent selected from lower alkanols (C1-C5) at a temperature between 20 ° C and 30 ° C in an amount of said solvent with respect to the aldehyde that allows the formation of a suspension of the Schiff base in a saturated solution of the base Schiff in the same solvent, and (ii), after termination of the iminoalkylation reaction is subjected to a reduction reaction with a reducing agent ion selected from sodium borohydride and potassi
