Salts of aripiprazole
The present invention relates to acid addition salts of aripiprazole, a process for preparing said acid addition salts and their use to prepare or purify aripiprazole in the form of a free base or in the form of a pharmaceutically acceptable salt.
1. A process for the production of aripiprazole or a pharmaceutically acceptable salt thereof comprising the steps of preparing and isolating an oxalic acid addition salt of aripiprazole or a solvate thereof and converting the oxalic acid addition salt or solvate thereof into aripiprazole in free form with less than 0.1% (w/w) of a compound of formula VII
and optionally converting the free form aripiprazole into a pharmaceutically acceptable salt of aripiprazole.
2. A process for the production of aripiprazole or a pharmaceutically acceptable salt thereof comprising the steps of
a) reacting a compound of formula
with a compound of formula
wherein X and Z are the same or different and each denote a halogen atom, or a group which is similar to halogen groups suitable to undergo a substitution reaction, to obtain a compound of formula
wherein X denotes as in formula III,
b) reacting a compound of formula IV as obtained from step a) with a compound of formula
to obtain a compound of formula
c) isolating the compound of formula VI as obtained in step b) in the form of an acid addition salt of formula
or a solvate thereof wherein Ac is oxalic acid, and
d) converting an acid addition salt of formula VIII as obtained in step c) into a compound of formula VI to isolate aripiprazole in free form with less than 0.1% (w/w) of a compound of formula VII
which is optionally further converted into a pharmaceutically acceptable salt of aripiprazole.
3. The process according to claim 2 which does not comprise any purification step of a compound of formula IV before reacting it with a compound of formula V.
4. The process according to claim 3 wherein aripiprazole in free form is isolated with less than 0.05% (w/w) of a compound of formula VII.
5. A process for the purification of aripiprazote by preparing an acid addition salt of formula VIII as defined in claim 2 , isolating said acid addition salt and converting it into aripiprazole in free form.
6. The process according to claim 5 wherein the aripiprazole isolated in free form is an aripiprazole which is substantially pure in terms of crystalline form, by using appropriate seed crystals and containing less than 0.1% of a compound of formula VII.
7. The acid addition salt of formula VIII as defined in claim 1 which is used in the preparation of aripiprazole.