Process for the preparation of exametazime

A process for the preparation of exametazime (formula I),

• which comprises the steps of:
• a) reacting 2,3-butanedione monoxime (formula II) with 2,2-dimethyl-1,3-propanediamine (formula III), in a suitable solvent, in presence of a dehydrating agent to afford diimine derivative 4,8-diaza-3,6,6,9-tetramethylundecane-3,8-diene-2,10-dione bisoxime (formula IV),
• b) reducing diimine derivative 4,8-diaza-3,6,6,9-tetramethylundecane-3,8-diene-2,10-dione bisoxime (formula IV) with a suitable reducing agent in a suitable solvent to afford a mixture of ‘d’, ‘l’ and meso isomers,
• c) optionally, purifying the mixture of ‘d’, ‘l’ and meso isomers,
• d) treating the mixture of ‘d’, ‘l’ and meso isomers with d or l chiral resolving acid to form corresponding acid addition salts, which are enantiomers of exametazime, and separating one of the enantiomers of exametazime as an acid addition salt,
• e) optionally, purifying the acid addition salt obtained in step (d),
• f) treating the mother liquor of step (d) with a suitable base,
• g) isolating a mixture of ‘d’ or ‘l’ enantiomers and meso isomers,
• h) purifying the mixture obtained in step (g),
• i) treating the mixture from step (h) with l or d chiral resolving acid to form corresponding acid addition salts, which are other enantiomers of exametazime and separating said other enantiomers of exametazime as acid addition salts,
• j) optionally, purifying the acid addition salts obtained in step (i),
• k) mixing the acid addition salt of step (d) or (e) and step (i) or (j),
• l) optionally, purifying the mixture of acid addition salts obtained in step (k),
• m) treating the mixture of acid addition salts of step (k) or (1) with a suitable base to afford exametazime and,
• n) optionally, purifying the exametazime.