Process for preparation of dronedarone by oxidation of a hydroxyl group

Patent metadata

Field	Value
Publication number	US-2016009678-A1
Application number	US-201314377484-A
Country	US
Kind code	A1
Filing date	Feb 14, 2013
Priority date	Feb 22, 2012
Publication date	Jan 14, 2016
Grant date	—

Abstract

The invention relates to a novel process for the preparation of dronedarone (I) and pharmaceutically acceptable salts thereof (formula I), which comprises oxidizing a compound of formula (VI), or a salt thereof and the obtained product is isolated and, if desired, converted into a pharmaceutically acceptable salt thereof. Further aspects of the invention include the novel intermediary compound of formula (VI) and process for the preparation thereof.

First claim

1 . Process for the preparation of dronedarone (I)

and pharmaceutically acceptable salts thereof characterized in that a compound of formula (VI) or a salt thereof

is oxidized,
and the obtained product is isolated and, if desired, converted into a pharmaceutically acceptable salt thereof.

2 . Process according to claim 1 characterized in that the oxidation is carried out with sodium hypochlorite or hydrogen peroxide in aqueous acidic medium.

3 . The compound of formula (VI) and salts thereof

4 . Process for the preparation of compound of formula (VI) and salts thereof characterized in that a compound of formula (II)

is reacted with compound of formula (V) or a salt thereof

in the presence of strong acid or base catalyst,
and the obtained product is isolated and, if desired, converted into a pharmaceutically acceptable salt thereof.

5 . Process according to claim 4 characterized in that the acid catalyst is trifluoroacetic acid.

6 . Process according to claim 4 characterized in that the base catalyst is butyl lithium.

7 . Process for preparation of dronedarone (I)

and pharmaceutically acceptable salts thereof according to claims 1 , 2 and 4 - 6 characterized in that
(a) a compound of formula (II) is reacted with the compound of formula (V) in the presence of strong acid or base catalyst to obtain a compound of formula (VI),
(b) the compound of formula (VI) is oxidized to obtain dronedarone (I),
and the obtained product is isolated and, if desired, converted into a pharmaceutically acceptable salt thereof.

Assignees

• Sanofi Sa

Inventors

• Huszár Csaba
• Hegedus Adrienn
• Dombrády Zsolt

Classifications

• C07D307/81 Primary

  Radicals substituted by nitrogen atoms not forming part of a nitro radical · CPC title

• C07D307/80 Primary

  Radicals substituted by oxygen atoms · CPC title