Patent ID: 8101750
Filing Date: 2012-01-24
Classification: A61P,C07D

Abstract:
1. A process for the manufacturing of a compound of formula (I), 2-hydroxy-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]1H-indole-5-carbonitrile, as a free base or a pharmaceutically acceptable salts thereof, by a) reacting a compound of formula (II) with a compound of formula R which is followed by bi) reacting the compound of formula (III) wherein R which is followed directly by step c) below, or alternatively bii) reacting a compound of formula (IV), wherein R in a solvent with morpholine optionally with a base to obtain compound of formula (V), or alternatively biii) reacting a compound of formula (IV) wherein R with methylmagnesium halide in the presence of iron (2,4-pentanedionate) followed by, c) reacting a compound of formula (V) with a carbonate of formula (X) wherein R in a solvent in the presence of a base to give a compound of formula (VI) wherein R which either is isolated, or its enolate is reacted further by, d) reacting the compound of formula (VI) wherein R in the presence of a base and a solvent, to form a compound of formula (VIII) wherein R followed by, e) reducing the compound of formula (VIII) with a suitable reducing agent in the presence of a solvent to selectively reduce the nitro group to an amine in the presence of the other functional groups to obtain a compound of formula (IX) wherein R followed by f) cyclisation the compound of formula (IX) with an acid to obtain a compound of formula (I), as a free base or a pharmaceutically acceptable salt thereof, or alternatively, h) reducing the compound of formula (VIII) with a suitable reducing agent in the presence of a solvent to obtain a compound of formula (XII) followed by k) reducing the compound of formula (XII) with a suitable reducing agent in the presence of a solvent to obtain a compound of formula (I), as a free base or a pharmaceutically acceptable salt thereof, or alternatively, l) reacting the compound of formula (IX) wherein R followed by m) reaction of the compound of formula (XIII) with a suitable acid in a solvent, to obtain a compound of formula (I), as a free base or a pharmaceutically acceptable salt thereof, the obtained free base or a pharmaceutically acceptable salt thereof, may optionally be further purified and isolated to obtain the pure free base or pharmaceutically acceptable salt thereof.