Sorbinil prepn. by optical resolution with amino:pinane derivs. - giving novel chiral amine salts as intermediates

摘要

Prepn. of sorbinil (I), or its pharmaceutically acceptable cationic salt, comprises (i) crystallising the (-)-3-aminomethyl pinane salt (IIa) of (I) from a soln. of racemic hydantoin of formula (III), and (ii) converting (IIa) to (I) or its salt. Alternatively, (a) either the (+)-3-aminomethyl pinane salt (IIb) or the (-)-2-amino-2-norpinane salt (IV) of the enantiomer of sorbinil is crystallised from a soln. of the racemic hydantoin of formula (III), (b) a concentrate of sorbinil is isolated from the mother liquor, (c) the quinine salt (V) of (I) is crystallised from a soln. of the concentrate; and (d) the quinine salt is converted to (I) or its salt. Also claimed are chiral amine salts of (I), i.e. (IIa), (IIb), (IV) and (V). (I) is a potent aldose reductase inhibitor, esp. useful in controlling the chronic complications of diabetes mellitus. Process gives good yields with much lower solvent vols., and avoids the use of a highly toxic resolving agent (brucine). The efficacy of the process is further enhanced by isolating and recycling the undesired enantiomer via 6-fluoro-4-chromanone.