PROCESSES FOR THE PREPARATION OF PALIPERIDONE AND PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF AND INTERMEDIATES FOR USE IN THE PROCESSES

摘要

Disclosed is a process for preparing paliperidone or a salt thereof comprising: (1) (a) condensing a 3-benzyloxy-2-aminopyridine (II) with an alpha-acyl lactone (V) in the presence of a catalytic amount of a dipolar aprotic solvent and an activating agent to obtain a compound of formula (III); (b) condensing the compound of formula (III) with a compound of formula (VI) or a salt thereof to obtain the compound of formula (VIII); (c) converting the compound of formula (VIII) to paliperidone by catalytic reduction; and (d) optionally converting paliperidone to a salt thereof; (2) (a) condensing a 3-benzyloxy-2-aminopyridine (II) with an alpha-acyl lactone (V) in the presence of a catalytic amount of a dipolar aprotic solvent and an activating agent to obtain a compound of formula (III); (b) catalytically reducing the compound of formula (III) to a compound of formula (IV) in the presence of an acid; (c) condensing chloroethyl derivative (IV) with compound (VI) or a salt thereof in the presence of a base to obtain paliperidone (I); and (d) optionally converting paliperidone to a salt thereof; or (3) (a) condensing a 3-benzyloxy-2-aminopyridine derivative (II) with an alpha-acyl lactone (V) in the presence of a catalytic amount of a dipolar aprotic solvent and an activating agent to obtain a compound of formula (III); (b) condensing the compound of formula (III) with a compound of formula (IX) to obtain a compound of formula (X); (c) converting the compound (X) to a compound of formula (XI) by catalytic reduction and cyclising the compound (XI) to obtain paliperidone; (d) and optionally converting paliperidone to a salt thereof.