Process for the preparation of rotigotine

Abstract

A process for the preparation of Rotigotine (1) and of pharmaceutically acceptable salts thereof, which comprises the reductive amination of an amine of formula 6 with the 2-thienylacetic acid-sodium boron hydride complex and which makes use of hydrobromide 5 as an intermediate The process is advantageous from the industrial point of view in that it allows to obtain Rotigotine with high enantiomeric purity starting from optically active 5,6,7, 8-tetrahydro-6-(S)-N-propylamino-1-methoxy-naphthalene (2), avoiding the use of dangerous reactives, the need for difficult chromatographic separation or the formation of by-products. Furthermore, two novel crystalline forms are disclosed.

1 . Rotigotine hydrochloride crystalline Form A characterized by the following IR, DSC and XRD spectra:
 IR (cm −1 ): 3074; 2946; 2621; 1732; 1589; 1464; 1367; 1275; 1083; 1025; 963; 850; 771; 729   DSC: onset temperature: 108.8° C.; peak temperature: 123.0° C.   X-ray spectrum (2θ): 7.1; 8.4; 9.8; 10.0; 13.2; 14.5; 14.8; 17.1; 17.8; 18.0; 18.8; 20.7; 22.9; 23.5; 25.4.   
     
     
         2 . Rotigotine hydrochloride crystalline Form B, characterized by the following IR, DSC and XRD spectra:
 IR (cm −1 ): 3058; 2966; 2633; 1588; 1464; 1436; 1347; 1275; 1207; 1161; 1086; 1049; 1027; 85; 950; 898; 850; 805; 772; 709.   DSC: onset temperature: 134.5° C.; peak temperature: 146.0° C.   X-ray spectrum (2θ): 6.9; 9.2; 9.3; 13.3; 14.8; 15.0; 17.6; 17.8; 19.2; 19.6; 20.8; 21.9; 23.2; 24.2; 24.6; 25.0.   
     
     
         3 . Pharmaceutical compositions containing Rotigotine hydrochloride Form A according to  claim 1  in admixture with pharmaceutically acceptable excipients and/or carriers. 
     
     
         4 . Pharmaceutical compositions containing Rotigotine hydrochloride Form B according to  claim 2  in admixture with pharmaceutically acceptable excipients and/or carriers.