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Process for the preparation of dronedarone

A reaction, n-butyl technology, applied in the field of new intermediates, can solve problems such as inability to remove

Inactive Publication Date: 2013-04-24
SANOFI SA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Another disadvantage of this method is that the reaction mixture used in the Friedel-Crafts reaction and the by-products obtained are insoluble in water, so they cannot be removed from the system by aqueous phase washing

Method used

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  • Process for the preparation of dronedarone
  • Process for the preparation of dronedarone

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0069] N-[2-n-butyl-3-{4-[(3-di-n-butylamino)-propoxy]-benzoyl}-1-benzofuran-5-yl]-methanesulfonamide (I)

[0070] A solution prepared by 5 g of sodium and 170 ml of absolute ethanol was added to 7 g of 2-n-butyl-3-[(di-n-butylamino)-3-propoxyl)-4-benzoyl]-5- In bis-(methylsulfonylamino)-benzofuran (II). The reaction mixture was boiled for 30 minutes and then evaporated under reduced pressure. 30 ml of dichloromethane and 50 ml of water were added to the residue, and the mixture was stirred for 20 minutes. The phases were separated. The organic phase was washed with 20 ml of water and evaporated.

[0071] Product: Oil (Yield: 97.9%). Purity (HPLC): 93.1%

[0072] The product was purified by its oxalate (yield: 90.3%). Purity (HPLC): 99.5%.

[0073] 1 H NMR(DMSO):0.8-0.9ppm(m,9H); 1.2-1.5ppm(m,10H); 1.67ppm(5',2H); 1.87ppm(5',2H); 2.38ppm(t,J =7.2Hz,4H); 2.57ppm(m,2H); 2.81ppm(t,J=7.5Hz,2H); 2.91ppm(s,3H); 4.15ppm(t,J=6.2Hz,2H); 7.09 (d, J=8.8Hz, 2H); 7.24ppm (dd, J=...

Embodiment 2

[0075] N-[2-n-butyl-3-{4-[(3-di-n-butylamino)-propoxy]-benzoyl}-1-benzofuran-5-yl]-methanesulfonamide (I)

[0076] The method of Example 1 was followed except methanol was used instead of ethanol.

[0077] Yield after purification: 88.6%. Purity (HPLC): 99.7%.

Embodiment 3

[0079] N-[2-n-butyl-3-{4-[(3-di-n-butylamino)-propoxy]-benzoyl}-1-benzofuran-5-yl]-methanesulfonamide (I)

[0080] The method of Example 1 was followed except that potassium was used instead of sodium.

[0081] Yield after purification: 88.9%. Purity (HPLC): 99.5%.

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Abstract

This invention relates to a process for the preparation of N-[2-n-butyl-3-{4-[(3- dibutylamino)-propoxy]-benzoyl} - 1-benzofuran-5-yl]-methane-sulfonamide of formula (I) and its pharmaceutically acceptable salts, according to one of the methylsulfonyl groups of the 2-n-butyl-3-[(di-n-butylamino-3-propoxy)-benzoyl]-5- bis-(methylsulfonamido)-benzofuran of formula (II) is selectively cleaved and if desired, the resulting compound of formula (I) is transformed into its salt.

Description

technical field [0001] The present invention relates to the preparation of N-[2-n-butyl-3-{4-[(3-di-n-butylamino)-propoxy]-benzoyl}-1-benzofuran-5-yl] - A new process for methanesulfonamide (dronedarone) and its pharmaceutically acceptable salts, and new intermediates used in the process. Background technique [0002] [0003] Dronedarone of formula I is used for the treatment of certain pathological changes of the cardiovascular system, above all for the treatment of angina, hypertension, arrhythmia and insufficient cerebral blood flow (EP0471609B1). [0004] Several methods for the preparation of dronedarone of formula I are currently known. In a prior art process (EP0471609B1), 2-n-butyl-5-nitro-benzofuran of formula IX [0005] [0006] React with anisyl chloride under Friedel-Crafts (Friedel-Crafts) conditions, and by heating the 2-n-butyl-3-(4-methoxy- Benzoyl)-5-nitro-benzofuran [0007] [0008] 2-n-Butyl-3-(4-hydroxy-benzoyl)-5-nitro-benzofuran of formu...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D307/80A61P9/00A61K31/343
CPCC07D307/80A61P9/00A61K31/343C07D307/79C07D307/82
Inventor A.弗赖兹
Owner SANOFI SA
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