WO2014203058A1

WO2014203058A1 - An improved process for preparing benzofuran compound

Info

Publication number: WO2014203058A1
Application number: PCT/IB2014/001064
Authority: WO
Inventors: Korrapati VENKATA VARA PRASADA RAO; Inti VENKATA SUBRAMANYESWARA RAO; Vysyaraju RAVI KANTH; Handa VIJAY KUMAR; Meenakshisunderam Sivakumaran
Original assignee: Aurobindo Pharma Limited
Priority date: 2013-06-17
Filing date: 2014-06-12
Publication date: 2014-12-24

Abstract

The present invention relates to a process for preparing Dronedarone or its pharmaceutically acceptable salts thereof, by reacting 5-amino-3-[4-(3-di-n-butyl aminopropoxy)benzoyl]-2-n-butyl benzofuran or a salt thereof with methanesulfonyl chloride in presence of a base.

Description

AN IMPROVED PROCESS FOR PREPARING BENZOFURAN COMPOUND

FIELD OF THE INVENTION The present invention relates to a process for the preparation of Dronedarone of Formula I.

BACKGROUND OF THE INVENTION

Dronedarone is chemically known as N-{2-Butyl-3-[4-(3-dibutylaminopropoxy) benzoyl]benzofuran-5-yl}methanesulfonamide and is being marketed as hydrochloride salt under the brand name Multaq® in the form of oral tablet. Dronedarone is useful in the treatment of certain pathological changes of the cardiovascular system, first of all in the treatment of angina pectoris, high blood pressure, arrhythmia and insufficient cerebral blood flow.

Dronedarone is disclosed in US Patent US 5,223,510. US '510 discloses a process for the preparation of Dronedarone, which is as shown below:

Methanesulfonylchloride

Dichloroethane

Triethylaminc

The present inventors observed that, use of triethylamine in the mesylation step as an acid acceptor results in the formation of higher amounts of bis-sulfonamide impurity (about 7% (during reaction monitoring by HPLC)) of Formula III. Therefore, an additional purification is required, which leads the process commercially not cost effective and also low ields.

IN 1080/CHE/2010, discloses a process to prepare Dronedarone by reacting 5-amino-3- [4-3-di-n-butylaminopropoxy)benzoyl]-2-n-butylbenzofuran or its acid addition salt with methane sulfonyl chloride in presence of sodium bicarbonate. However, the present inventors have repeated this experiment and found that the reaction mass becomes sticky and reaction has not proceeded further. To overcome the prior-art problems the present inventors have now developed process for preparing Dronedarone or its pharmaceutically acceptable salts, which commercially cost effective with high yields. OBJECTIVE OF THE INVENTION

The main objective of the present invention is to provide a process for preparing Dronedarone or its pharmaceutically acceptable salts, which is simple, industrially applicable and cost effective.

Yet another objective of the present invention is to provide a process for preparing Dronedarone or its pharmaceutically acceptable salts, which is substantially free of bis- sulfonamide impurity. SUMMARY OF THE INVENTION

The present invention relates to a process for the preparation of Dronedarone of Formula I, or its pharmaceutically acceptable salts, which comprises,

a) reacting 5 -amino-3 - [4-3 -di-n-butylaminopropoxy)benzoyl] -2-n-butylbenzofuran or a salt thereof of Formula II,

with methanesulfonyl chloride in presence of a base; and

b) isolating the compound of Formula I,

wherein base is selected from group comprising of alkaline earth metal oxides, quinoline and lutidine. DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to a process for preparing Dronedarone or its pharmaceutically acceptable salts thereof, by reacting 5-amino-3-[4-(3-di-n-butyl aminopropoxy)benzoyl]-2-n-butyl benzofuran or a salt thereof with methanesulfonyl chloride in presence of a base selected from the group comprising of alkaline earth metal oxide or quinoline or lutidine; in presence of a solvent at a temperature ranging from 0-50°C, preferably at 20-30°C. In another aspect of the present invention, 5-amino-3-[4-(3-di-n-butyl aminopropoxy)benzoyl]-2-n-butyl benzofuran or a salt thereof, wherein the salt is selected from the group comprising of oxalate, succinate, maleate and the like

In yet another aspect of the present invention, alkaline earth metal oxide is selected from the group comprising of calcium oxide, magnesium oxide, barium oxide and the like.

In yet another aspect of the present invention, the solvent is selected from group comprising of alkyl esters, halogenated hydrocarbons and the like and mixtures thereof.

In yet another aspect of the present invention, solvent is selected from group comprising of ethyl acetate, methyl acetate, butyl acetate, methylene chloride, ethylene chloride, chloroform, chlorobenzene, dichlorobenzene and the like and mixtures thereof.

In yet another aspect of the present invention, Dronedarone obtained according to the present invention is free of bis-sulfonamide impurity, which is as shown below:

In yet another aspect of the invention the Dronedarone obtained is optionally isolated or in situ converted to its pharmaceutically acceptable salt thereof.

In another aspect of the present invention the pharmaceutically acceptable salt is selected from the group comprising of hydrochloride, hydrobromide, oxalte, sulfate and the like.

In another aspect of the present invention the salt is hydrochloride. In another aspect of the present invention, Dronedarone hydrochloride is prepared by reacting Dronedarone with hydrochloric acid in presence of a solvent at a temperature ranging from 0-50°C, preferably at 20-30°C.

In another aspect of the present invention, the solvent is selected from group comprising of alcohols, alkyl esters, acetone, water and mixtures thereof.

In another aspect of the present invention, the solvent is selected from group comprising of methanol, ethanol, isopropanol, tert-butyl alcohol, ethyl acetate, methyl acetate, butyl acetate and the like.

In another aspect of the present invention, Dronedarone hydrochloride is optionally purified, by dissolving Dronedarone hydrochloride in a solvent, heating, optionally carbon treatment, concentrate and then cooling, wherein solvents selected from the group comprising of acetone, methanol, ethanol, isopropanol, tert-butyl alcohol and the like.

In another aspect of the present invention, 5-amino-3-[4-3-di-n- butylaminopropoxy)benzoyl]-2-n-butylbenzofuran is prepared by the following process or by using the process disclosed in the prior-art. 5-Amino-3-[4-3-di-n-butylaminopropoxy)benzoyl]-2-n-butylbenzofuran is prepared by catalytic hydrogenation of 2-butyl-3-[4-(3-dibutylaminopropoxy)benzoyl]-5- nitrobenzofuran in the presence of a catalyst, selected from the group comprising of palladium-carbon, platinum oxide, Raney nickel and hydrogen, solvent selected from group comprising of methanol, ethanol, isopropanol, butanol, ethyl acetate, methyl acetate, butyl acetate, toluene, xylene and mixture thereof at a temperature ranging from 20- 100°C, preferably at 30-50°C.

2-Butyl-3-[4-(3-dibutylaminopropoxy)benzoyl]-5-nitrobenzofuran is prepared by condensing 2-butyl-3-(4-hydroxybenzoyl)-5-nitrobenzofuran with N-(3-chloropropyl) dibutylamine, in presence of anhydrous potassium carbonate and a solvent at a temperature ranging from 40-100°C, preferably at 50-80°C.

The solvent is selected from group comprising of methyl ethyl ketone, acetone, acetonotrile, dimethylformamide, dimethylacetamide, Dimethylsulfoxide, N-methyl pyrrolidone and mixtures thereof.

The following examples illustrate the nature of the invention and are provided for illustrative purposes only and should not be construed to limit the scope of the invention in any manner whatsoever.

EXAMPLE 1

Preparation of 2-Butyl-3-[4-(3-dibutylaminopropoxy)benzoyl]-5-nitrobenzofuran 2-Butyl-3-(4-hydroxybenzoyl)-5-nitrobenzofuran (300 g) was dissolved in methyl ethyl ketone (1500 ml) and added anhydrous potassium carbonate powder (183.20 g) followed by N-(3-chloropropyl)dibutylamine (190.95 g) at 25-30°C. Thereafter the reaction mass was heated to reflux and continued stirring at reflux temperature till completion of the reaction. The obtained reaction mass was cooled to 25-30°C, filtered through hyflo to remove the inorganic salts and washed the residue with methyl ethyl ketone (600 ml, 25-30°C). The filtrate was concentrated under reduced pressure (250- 15 mm Hg) at 50-80°C till no more solvent distils to afford 2-Butyl-3-[4-(3- dibutylaminopropoxy)benzoyl]-5-nitrobenzofuran as a viscous liquid and was taken as such for the next step.

Yield: 450 g

Chromatographic Purity (by HPLC): 99.39% EXAMPLE 2

Preparation of 5-amino-3-[4-3-di-n-butylaminopropoxy)benzoyl]-2-n-butyl benzofuran dioxalate

2-butyl-3-[4-(3-dibutylaminopropoxy)benzoyl]-5-nitrobenzofuran (300 g) was dissolved in ethanol (Absolute alcohol, 1500 ml) and added 5% w/w palladium on carbon (30 g, 50% wet) at 25-30°C. The reaction mass was hydrogenated by maintaining, 4.5-5 Kg/cm pressure of hydrogen at 25-35°C till completion of the reaction. Filtered the catalyst and washed the residue with ethanol (Absolute alcohol, 600 ml) at 25-35°C. To the filtrate oxalic acid dihydrate (145 g) was added at 25-30°C. The reaction mass was heated to 40-45°C and then stirred for 30 min. Cooled to 25- 30°C and again stirred for 1 h. Filtered the product and washed with ethanol (Absolute alcohol, 450 ml, 25-30°C). Dried the product at 65-70°C under reduced pressure to yield 5-amino-3-[4-3-di-n-butylaminopropoxy)benzoyl]-2-n-butyl benzofuran dioxalate as a pale yellow crystalline powder

Yield: 345 g

Chromatographic Purity (by HPLC): 99.06 % EXAMPLE 3

2-butyl-3-[4-(3-dibutylaminopropoxy)benzoyl]-5-nitrobenzofuran (300g) was dissolved in aqueous ethanol (1500 ml) and added 5% w/w palladium on carbon (30 g, 50% wet) at 25-30°C. The reaction mass was hydrogenated by maintaining, 4.5-5 Kg/cm² pressure of hydrogen at 25-35°C till completion of the reaction. Filtered the catalyst and washed the residue with aqueous ethanol (600 ml) at 25 - 35°C. To the filtrate oxalic acid dihydrate (145 g) was added at 25-30°C. The reaction mass was heated to 40-45°C and then stirred for 30 min. Cooled to 25-30°C and again stirred for 1 h. Filtered the product and washed with aqueous ethanol (450 ml). Dried the product at 65-70°C under reduced pressure to yield 5-amino-3-[4-3-di-n- butylaminopropoxy)benzoyl]-2-n-butyl benzofuran dioxalate as pale yellow crystalline powder

Yield: 340 g

Chromatographic Purity (by HPLC): 99.09% EXAMPLE 4

2-butyl-3-[4-(3-dibutylaminopropoxy)benzoyl]-5-nitrobenzofuran (50 g) was dissolved in ethanol (Absolute alcohol, 250 ml) and added 5% w/w palladium on carbon (1.5 g, 50% wet) at 25-30°C. The reaction mass was hydrogenated by maintaining, 4.5-5 Kg/cm² pressure of hydrogen at 45-50°C till completion of the reaction. Filtered the catalyst and washed the residue with ethanol (Absolute alcohol, 100 ml) at 25 - 35°C. To the filtrate oxalic acid dihydrate (24.2 g) was added at 25-30°C. The reaction mass was heated to 40-45°C and then stirred for 30 min. Cooled to 25-30°C and again stirred for 1 h. Filtered the product and washed with ethanol (Absolute alcohol, 75 ml, 25- 30°C). Dried the product at 65-70°C under reduced pressure to yield 5-amino-3-[4-3- di-n-butylaminopropoxy)benzoyl]-2-n-butyl benzofuran dioxalate as a pale yellow crystalline powder

Yield: 57.5 g

Chromatographic Purity (by HPLC): 99.05 % EXAMPLE 5 Preparation of 5-amino-3-[4-3-di-n-butylaminopropoxy)benzoyI]-2-n-butyl benzofuran dioxalate

2-butyl-3-[4-(3-dibutylaminopropoxy)benzoyl]-5-nitrobenzofuran (300g) was dissolved in aqueous ethanol (1500 ml) and added Raney nickel (60 g) at 25-30°C. The reaction mass was hydrogenated by maintaining, 4.5-5 Kg/cm² pressure of hydrogen at 25-35°C till completion of the reaction. Thereafter, filtered the catalyst and washed the residue with aqueous ethanol (600 ml) at 25 - 35°C. To the filtrate oxalic acid dihydrate (145 g) was added at 25-30°C. The reaction mass was heated to 40-45°C and then stirred for 30 min. Cooled to 25-30°C and again stirred for 1 h. Filtered the product and washed with aqueous ethanol (450 ml). Dried the product at 65-70°C under reduced pressure to yield 5-amino-3-[4-3-di-n-butylaminopropoxy)benzoyl]-2-n-butyl benzofuran dioxalate as a pale yellow crystalline powder

Yield: 318 g

Chromatographic Purity (by HPLC): 97.96 %

EXAMPLE 6

2-Butyl-3-[4-(3-dibutylaminopropoxy)benzoyl]-5-nitrobenzofuran (25 g) was dissolved in ethanol (Absolute alcohol, 100 ml) and added activated carbon. Stirred for 30 minutes, filtered the carbon and washed with ethanol (25 ml). To the filtrate, 5% w/w palladium on carbon (0.75 g, 50% wet) was added at 25-30°C. The reaction mass was hydrogenated by maintaining, 4.5-5 Kg/cm² pressure of hydrogen at 45-50°C till completion of the reaction. Thereafter, filtered the catalyst and washed the residue with ethanol (Absolute alcohol, 50 ml) at 25 - 35°C. To the filtrate oxalic acid dihydrate (12.4 g) was added at 25-30°C. The reaction mass was heated to 40-45°C and then stirred for 30 min. Cooled to 25-30°C and again stirred for 1 h. Filtered the product and washed with ethanol (50 ml,). Dried the product at 65-70°C under reduced pressure to yield 5-amino-3-[4-3-di-n-butylaminopropoxy)benzoyl]-2-n-butyl benzofuran dioxalate as a pale yellow crystalline powder. Yield: 16.5 g

Chromatographic Purity (by HPLC): 99.92 %

EXAMPLE 7 Preparation of Dronedarone Hydrochloride

2-butyl-3-[4-(3-dibutylaminopropoxy)benzoyl]-5-aminobenzofuran dioxalate salt (250 g) was suspended in to a mixture of methylene chloride (750 ml) and DM water (750 ml) at 25-30°C. To the reaction mass, aqueous sodium bicarbonate (-3060 ml, prepared by dissolving 159.60 g of sodium bicarbonate in 3.0 Lt of DM water) was added slowly at 25-30°C in -30 min. Thereafter, stirred the contents at 20-30°C for 15 min. Separated the layers, extracted the aqueous layer with methylene chloride (500 ml) at 25-30°C and washed the combined organic layer with DM water (2 x 1250 ml) at 25- 30°C. To the obtained organic layer, calcium oxide (21.30 g) was added at 25-30°C and then a solution of methanesulfonyl chloride (-190 ml, prepared by mixing 78.30 g of methanesulfonyl chloride in 125 ml of methylene chloride) was added at 25-30°C over a period of -30 min. Thereafter, continued stirring at 25-30°C till completion of the reaction. To the resulting reaction mass, DM water (500 ml) and hydrochloric acid (91 g, -32% w/w) were added at 25-30°C for -45 min. Separated the layers and extracted the aqueous layer with methylene chloride (250 ml) at 25-30°C. Combined the organic layer and washed with DM water (2 x 500 ml) at 25-30°C. Concentrated the organic layer (-1450 ml) at atmospheric pressure till the mass temperature reaches 60-65°C. The obtained concentrated mass was cooled to 50-55°C and then added acetone (1350 ml). Again, concentrated the reaction mass at atmospheric pressure to collect -250 ml of the distillate. The obtained concentrated mass was cooled to 25-30°C and stirred for 30 min. Cooled the suspension to -12 to -8°C and continued stirring for 1 h at -12 to - 8°C. Filtered the obtained product at -12 to -8°C and washed with pre-cooled acetone (300 ml, -12 to -8°C). The filtered wet mass was suspended in acetone (3.24 Lt) and added carbon (25 g) at 25-30°C. Heated the contents to reflux at 55-60°C and stirred for 30 min. The obtained reaction mass was cooled to 45-50°C, filtered the carbon through hyflo and washed the residue with pre-heated acetone (360 ml, 45-50°C). The obtained filtrate was concentrated (-3.65 Lt) at atmospheric pressure at 55-60°C to a volume of -1200 ml. Cooled the concentrated mass to 25-30°C and continued stirring for 30 min. Thereafter, cooled the slurry to -12 to -8°C, stirred for 1 h, filtered the product and washed with pre-cooled acetone (300 ml, -12 to -8°C). The product obtained was dried at 65-70°C under reduced pressure to yield Dronedarone hydrochloride as a white to off-white crystalline powder having any single impurity less than 0.10%.

Yield: 165 g

Chromatographic Purity (by HPLC): 99.91 % EXAMPLE 8

Preparation of Dronedarone Hydrochloride

2-butyl-3-[4-(3-dibutylaminopropoxy)benzoyl]-5-aminobenzofuran dioxalate salt (250 g) was suspend in to a mixture of methylene chloride (750 ml) and DM water (750 ml) at 25-30°C. To the reaction mass aqueous sodium bicarbonate (-3060 ml, prepared by dissolving 159.60 g of sodium bicarbonate in 3.0 Lt of DM water) was added slowly at 25-30°C in -30 min. Thereafter, stirred the contents at 20-30°C for 15 min. Separated the layers, extracted the aqueous layer with methylene chloride (500 ml) at 25-30°C and washed the combined organic layer with DM water (2 x 1250 ml) at 25-30°C. To the obtained organic layer, quinoline (49 g) is added at 25-30°C and then a solution of methanesulfonyl chloride (-190 ml, prepared by mixing 78.30 g of methanesulfonyl chloride in 125 ml of methylene chloride) was added at 25-30°C over a period of -30 min. Thereafter, continue stirring at 25-30°C till completion of the reaction. To the resulting reaction mass DM water (500 ml) and hydrochloric acid (91 g, -32% w/w) was added at 25-30°C for -45 min. Separated the layers and extracted the aqueous layer with methylene chloride (250 ml) at 25-30°C. Combined the organic layer and washed with DM water (2 x 500 ml) at 25-30°C. Concentrated the organic layer (-1450 ml) at atmospheric pressure till the mass temperature reaches 60-65°C. The obtained concentrated mass was cooled to 50-55°C and then added acetone (1350 ml. Again, concentrated the reaction mass at atmospheric pressure to collect -250 ml of the distillate. The obtained concentrated mass was cooled to 25-30°C and stirred for 30 min. Cooled the suspension to -12 to -8°C and continued stirring for 1 h at -12 to -8°C. Filtered the obtained product at -12 to -8°C and washed with pre-cooled acetone (300 ml, -12 to -8°C). The filtered wet mass was suspended in acetone (3.24 Lt) and added carbon (25 g) at 25-30°C. Heat the contents to reflux at 55-60°C and stirred for 30 min. The obtained reaction mass was cooled to 45-50°C, filtered the carbon through hyflo and washed the residue with pre-heated acetone (360 ml, 45-50°C). The obtained filtrate was concentrated (-3.65 Lt) at atmospheric pressure at 55-60°C to a volume of -1200 ml. Cooled the concentrated mass to 25-30°C and continued stirring for 30 min. Thereafter, cooled the slurry to -12 to -8°C, stirred for 1 h, filtered the product and washed with pre-cooled acetone (300 ml, -12 to -8°C). The product obtained was dried at 65-70°C under reduced pressure to obtain Dronedarone hydrochloride as white to off-white crystalline powder having any single impurity less than 0.10%.

Yield: 165 g

Chromatographic Purity (by HPLC): 99.8 %

EXAMPLE 9

Preparation of Dronedarone Hydrochloride

2-Butyl-3-[4-(3-dibutylaminopropoxy)benzoyl]-5-nitrobenzofuran (50 g) was dissolved in ethanol (Absolute alcohol, 200 ml) and added activated carbon. Stirred for 30 minutes, filtered the carbon and washed with ethanol (50 ml). To the filtrate, 5% w/w palladium on carbon (1.5 g, 50% wet) was added at 25-30°C. The reaction mass was hydrogenated by maintaining, 4.5-5 Kg/cm² pressure of hydrogen at 45-50°C till completion of the reaction. Thereafter, filtered the catalyst and washed the residue with ethanol (Absolute alcohol, 100 ml) at 25 - 35°C. Distilled of the ethanol solvent from the filtrate under reduced pressure at below 50°C to obtain 5-amino-3-[4-3-di-n- butylaminopropoxy)benzoyl]-2-n-butyl benzofuran as a pale yellow oily mass. Dissolve the obtained oily mass in methylene chloride (150 ml) at 25-30°C and washed with water (2 x 150 ml). To the obtained organic layer, quinoline (12.5 g) is added at 25-30°C and then a solution of methanesulfonyl chloride (prepared, by mixing 19.72 g of methanesulfonyl chloride in 50 ml of methylene chloride) was added at 25-30°C over a period of -30 min. Thereafter, continue stirring at 25-30°C till completion of the reaction. To the resulting reaction mass DM water (100 ml) and hydrochloric acid (23.5 g, -32% w/w) were added at 25-30°C for -45 min. Separated the layers, extracted the aqueous layer with methylene chloride (100 ml) at 25-30°C and washed the combined organic layer with DM water (2 x 100 ml). Concentrate the organic layer at atmospheric pressure till the mass temperature reaches 60-65°C. The obtained concentrated mass was cooled to 50-55°C and then added acetone (300 ml). Again concentrated the reaction mass at atmospheric pressure and collected -50 ml of the distillate. The obtained concentrated mass was cooled to 25-30°C, stirred for 30 min. The concentrated mass was further cooled to -12 to -8°C, stirred for 1 h at -12 to -8°C, filtered the obtained product and washed with pre-cooled acetone (300 ml, -12 to -8°C). The product was crystallized from acetone to yield Dronedarone hydrochloride as almost white crystalline powder.

Yield: 38 g

Chromatographic Purity (by HPLC): 99.75% EXAMPLE 10

Preparation of Dronedarone Hydrochloride

2-butyl-3-[4-(3-dibutylaminopropoxy)benzoyl]-5-nitrobenzofuran (50 g) was dissolved in ethanol (Absolute alcohol, 200 ml) and added activated carbon. Stirred for 30 minutes, filtered the carbon and washed with ethanol (50 ml). To the filtrate, 5% w/w palladium on carbon (1.5 g, 50% wet) was added at 25-30°C. The reaction mass was hydrogenated by maintaining, 4.5-5 Kg/cm² pressure of hydrogen at 45-50°C till completion of the reaction. Thereafter, filtered the catalyst and washed the residue with ethanol (Absolute alcohol, 100 ml) at 25 - 35°C. Distilled of the ethanol solvent from the filtrate under reduced pressure at below 50°C to obtain 5-amino-3-[4-3-di-n- butylaminopropoxy)benzoyl]-2-n-butyl benzofuran as a pale yellow oily mass. To the obtained organic layer, calcium oxide (6.006 g) is added at 25-30°C and then a solution of methanesulfonyl chloride (prepared by mixing 19.72 g of methanesulfonyl chloride in 50 ml of methylene chloride) was added at 25-30°C over a period of -30 min. Thereafter, continue stirring at 25-30°C till completion of the reaction. To the resulting reaction mass DM water (100 ml) and hydrochloric acid (23.5 g, -32% w/w) were added at 25-30°C for -45 min. Separated the layers and extracted the aqueous layer with methylene chloride (100 ml) at 25-30°C. Wash the combined organic layer with DM water (2 x 100 ml) at 25-30°C. Concentrate the organic layer at atmospheric pressure till the mass temperature reaches 60-65 °C. The obtained concentrated mass was cooled to 50-55°C and then added acetone (300 ml). Again, concentrate the reaction mass at atmospheric pressure to collect -50 ml of the distillate. The obtained concentrated mass was cooled to 25-30°C and stirred for 30 min. The concentrated mass was further cooled to -12 to -8°C, stirred for 1 h at -12 to -8°C, filtered the obtained product and washed with pre-cooled acetone (300 ml, -12 to -8°C). The product was crystallized from acetone to yield Dronedarone hydrochloride as almost white crystalline powder.

Yield: 38 g

Chromatographic Purity (by HPLC): 99.75%

Claims

We claim

1. A process for the preparation of Dronedarone of Formula I, or its pharmaceutically acceptable salts, which comprises:

a) reacting 5-amino-3-[4-3-di-n-butylaminopropoxy)benzoyl]-2-n-butylbenzofuran or a salt thereof of Formula II

with methanesulfonyl chloride in presence of a base; and

b) isolating the compound of Formula I,

wherein the base is selected from group comprising of alkaline earth metal oxides, quinoline and lutidine.

2. The process according to claim 1, wherein salt of 5-amino-3-[4-(3-di-n-butyI aminopropoxy)benzoyl]-2-n-butyl benzofuran is selected from the group comprising of oxalate, succinate, maleate and the like.

3. The process according to claim 1, wherein alkaline earth metal oxide is selected from the group comprising of calcium oxide, magnesium oxide, barium oxide and the like.

4. The process according to claim 1 , wherein the solvent is selected from the group comprising of alkyl esters, halogenated hydrocarbons and mixtures thereof.

5. The process according to claim 4, wherein solvent is selected from group comprising of ethyl acetate, methyl acetate, butyl acetate, methylene chloride, ethylene chloride, chloroform, chlorobenzene, dichlorobenzene and mixtures thereof.

6. Dronedarone prepared according to claim 1 , wherein the said Dronedarone containing bis-sulfonamide impurity < 0.5%, as determined by HPLC.

7. The process according to claim 1 , wherein Dronedarone is optionally isolated, and converted in to pharmaceutically acceptable salt thereof, preferably hydrochloride salt.

8. The process according to claim 1 , which further comprises purification of Dronedarone hydrochloride.

9. The process according to claim 8, wherein the purification of Dronedarone hydrochloride comprises:

a) dissolving Dronedarone hydrochloride in a solvent;

b) heating;

c) optionally treating with carbon and concentration;

d) cooling; and

e) isolating the pure Dronedarone hydrochloride.

10. The process according to claim 9, wherein the solvent is selected from the group comprising of acetone, methanol, ethanol, isopropanol, tert-butyl alcohol and the like.