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A Process for the Preparation of Dofetilide

IP.com Disclosure Number: IPCOM000244364D
Publication Date: 2015-Dec-07
Document File: 3 page(s) / 102K

Publishing Venue

The IP.com Prior Art Database

Abstract

The present invention relates to a process for the preparation of Dofetilide by condensation, conventional reduction and sulfonylation reaction.

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This is the abbreviated version, containing approximately 50% of the total text.

Page 01 of 3

A PROCESS FOR THE PREPARATION OF DOFETILIDE


[0001] Dofetilide is chemically known as

[(methylsulfonyl)amino]phenoxy]ethyl]amino]ethyl]phenyl]methanesulfonamide.

[0002] The present document discloses a process for the preparation of Dofetilide comprising the steps of: a) condensing N-methyl-2-(4-nitrophenyl)ethylamine hydrochloride with 2-[4- nitrophenoxy]ethyl chloride in presence of a base to produce N-methyl-N-[2-(4- nitrophenoxy)ethyl]-4-nitrophenethylamine;

b) treating N-methyl-N-[2-(4-nitrophenoxy)ethyl]-4-nitrophenethylamine with an acid to isolate an acid addition salt of N-methyl-N-[2-(4-nitrophenoxy)ethyl]-4- nitrophenethylamine and optionally purified the acid addition salt of N-methyl-N- [2-(4-nitrophenoxy)ethyl]-4-nitrophenethylamine;

c) reducing the product of step-(b) in presence of a catalyst to produce N-methyl-N-[2- (4-aminophenoxy)ethyl]-4-aminophenethylamine;

d) sulfonylating N-methyl-N-[2-(4-aminophenoxy)ethyl]-4-aminophenethylamine to produce Dofetilide.

wherein, the base in step-(a) comprises alkali or alkaline earth metal hydroxides such as lithium hydroxide, sodium hydroxide, potassium hydroxide, calcium hydroxide, aluminum hydroxide, magnesium hydroxide, an alkali metal carbonates, such as sodium carbonate or potassium carbonate; an alkali metal hydrogencarbonates, such as sodium hydrogencarbonate or potassium hydrogencarbonate; alakali metal hydrides such as sodium hydride, potassium hydride; or organic base such as triethylamine and the like or mixture thereof

The acid used in step-(b) selected from organic acids such as formic acid, acetic acid, oxalic acid, methanesulfonic acid, p-toluenesulfonic acid and trifluoroacetic acid; or inorganic acids, such as hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid or nitric acid.

1

N

-[4-[2-[methyl[2-[4-


Page 02 of 3

The acid addition salt of N-methyl-N-[2-(4-nitrophenoxy)ethyl]-4-nitrophenethylamine is isolated and optionally purified by known methods, for example by dissolving in a solvent selected from the group comprising toluene, methanol, ethanol, isopropanol, ethyl acetate, methylene chloride, hexane, heptane, cyclohexane, acetone, THF, water or mixtures thereof; and precipitating pure compound by cooling the solution or by adding an anti solvent.

The catalyst used in step-(c) selected from palladium-on-carbon, platinum(IV) oxide, or Raney nickel.

The reaction of step-(d) is carried out in presence of a base selected from organic base such as triethylamine, diethylamine, diisopropylethyl amine, butylammine or inorganic base such as aqueous solution of alkali metal carbonate such as sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate; alkali metal hydroxide such as sodium hydroxide, potassium hydroxide .

The process of each Step-(a), Step-(b), Step-(c), and Step-(d) is carried out in presence of a solvent.

The solvent used in the each step is selected from toluene, ethyl acetate, tetrahydrofuran, methanol, eth...