Process for the preparation of lomitapide

Patent metadata

Field	Value
Publication number	US-10023526-B2
Application number	US-201515524391-A
Country	US
Kind code	B2
Filing date	Nov 4, 2015
Priority date	Nov 5, 2014
Publication date	Jul 17, 2018
Grant date	Jul 17, 2018

Abstract

The present invention relates to a process for preparing Lomitapide or its pharmaceutically acceptable salt thereof having high purity with acceptable levels of impurities.

First claim

We claim:

1. A process for the preparation of a bromobutyl 9H-fluorene carboxamide of Formula II,

which comprises:
i) condensing a 9H-fluorene-9-carboxylic acid of Formula IV

with 4-bromobutyl acetate to yield a 9-(4-acetoxybutyl)-9H-fluorene-9-carboxylic acid of Formula V;

ii) optionally isolating the compound of Formula V;
iii) reacting the compound of Formula V with an alkali hydroxide solution to yield a 9-(4-hydroxybutyl)-9H-fluorene-9-carboxylic acid of Formula VI;

iv) reacting the compound of Formula VI with 2,2,2-trifluoroethane-1-amine hydrochloride salt to yield a 9-(4-hydroxybutyl)-N-(2,2,2-trifluoroethyl)-9H-fluorene-carboxylic acid of Formula VII;

v) reacting the compound of Formula VII with bromine to yield the bromobutyl 9H-fluorene carboxamide of Formula II; and
vi) optionally purifying the compound of Formula II.

2. The process as claimed in claim 1 , wherein a solvent is used in step i) and the solvent is selected from the group consisting of alcohols, halogenated hydrocarbons, polar aprotic solvents, and non-polar solvents, wherein the alcohols are selected from the group consisting of aliphatic alcohols and aromatic alcohols; the halogenated hydrocarbons are chlorinated hydrocarbons; and the polar aprotic solvents are selected from the group consisting of organic nitriles, amides, ketones, ethereal solvents, esters, and mixtures thereof.

3. The process as claimed in claim 1 , wherein a base is used in step i) and the base is selected from the group consisting of triethyl amine, n-butyl lithium, sec-butyl lithium, sodium hydride, potassium hydride, sodium hydroxide, and potassium hydroxide.

4. The process as claimed in claim 1 , wherein the alkali hydroxide used in step iii) is selected from the group consisting of sodium hydroxide, potassium hydroxide, and lithium hydroxide.

5. A compound 9-(4-acetoxybutyl)-9-H-fluorene-9-carboxylic acid of Formula V

Assignees

• Hetero Research Foundation

Inventors

• Parthasaradhi Reddy Bandi
• Rathnakar Reddy Kura
• Vamsi Krishna Bandi
• Mukunda Reddy Jambula

Classifications

• C07C67/293

  by isomerisation; by change of size of the carbon skeleton · CPC title

• C07D211/58

  attached in position 4 · CPC title

• C07C62/32

  containing hydroxy or O-metal groups · CPC title

• C07C231/12

  by reactions not involving the formation of carboxamide groups · CPC title

• C07C51/367

  by introduction of functional groups containing oxygen only in singly bound form · CPC title