500791-70-8

Basic information

• Product Name: (5-Amino-2-butyl-3-benzofuranyl)[4-[3-(dibutylamino)propoxy]phenyl]-methanone ethanedioate
• Synonyms: (5-Amino-2-butyl-3-benzofuranyl)[4-[3-(dibutylamino)propoxy]phenyl]-methanone ethanedioate;(5-AMino-2-butylbenzofuran-3-yl)(4-(3-(dibutylaMino)propoxy)phenyl)Methanone oxalate;(5-aMino-2-butylbenzofuran-3-yl)(4-(3-(dibutylaMino)propoxy)phenyl)Methanone dioxalate;(5-aMino-2-butyl-3-benzofuranyl)[4-[3-(dibutylaMino) propoxy]phenyl]-Methanone dioxalate;Des(Methylsulfonyl) Dronedarone Oxalate;Dronedarone Hydrochloride IMpurity A;(4-(3-(dibutylamino);(5-Amino-2-butylbenzofuran-3-yl)
• CAS NO: 500791-70-8
• Molecular Formula: C30H42N2O3.2(C2H2O4)
• Molecular Weight: 658.75
• EINECS: 1806241-263-5
• Mol File: 500791-70-8.mol

Chemical Properties

• Appearance: /
• Storage Temp.: Keep in dark place,Inert atmosphere,Room temperature
• Solubility: DMSO (Slightly), Methanol (Slightly)
• CAS DataBase Reference: (5-Amino-2-butyl-3-benzofuranyl)[4-[3-(dibutylamino)propoxy]phenyl]-methanone ethanedioate(CAS DataBase Reference)
• NIST Chemistry Reference: (5-Amino-2-butyl-3-benzofuranyl)[4-[3-(dibutylamino)propoxy]phenyl]-methanone ethanedioate(500791-70-8)
• EPA Substance Registry System: (5-Amino-2-butyl-3-benzofuranyl)[4-[3-(dibutylamino)propoxy]phenyl]-methanone ethanedioate(500791-70-8)

Safety Data

• Hazardous Substances Data: 500791-70-8(Hazardous Substances Data)

Usage

InChI:InChI=1/C30H42N2O3.2C2H2O4/c1-4-7-11-28-29(26-22-24(31)14-17-27(26)35-28)30(33)23-12-15-25(16-13-23)34-21-10-20-32(18-8-5-2)19-9-6-3;2*3-1(4)2(5)6/h12-17,22H,4-11,18-21,31H2,1-3H3;2*(H,3,4)(H,5,6)

Upstream product

• 526196-92-9 (2-n-butyl-benzofuran-5-yl)-acetamide 
• 1278585-69-5 N-(2-butyl-3-(4-(3-(dibutylamino)propoxy)benzoyl)benzofuran-5-yl)acetamide 
• 144-62-7 oxalic acid 
• 1278585-66-2 2-n-butyl-3-(4-hydroxybenzoyl)-5-acetamidobenzofuran 
• 1278585-63-9 2-n-butyl-3-(4-methoxybenzoyl)-5-acetamidobenzofuran 
• 111-92-2 dibutylamine 
• 65136-52-9 4-(3-chloropropoxy)benzoic acid 
• 65136-48-3 4-(3-chloropropoxy)benzoic acid chloride 
• 526196-90-7 2-n-butyl-5-aminobenzofuran hydrochloride 
• 1365546-06-0 3-[4-(3-chloropropoxy)benzoyl]-2-n-butylbenzofuran-5-yl-1H-isoindole-1,3(2H)dione 
• 1365546-05-9 2-(-2-butyl-1-benzofuran-5-yl)-1H-isoindole-1,3(2H)dione 
• 6153-56-6 oxalic acid dihydrate 
• 1365546-07-1 C₃₈H₄₄N₂O₅ 
• 36421-15-5 dibutyl-(3-chloro-propyl)-amine 

Downstream Products

• 141644-91-9 (5-amino-2-butyl-benzofuran-3-yl)-[4-(3-dibutylamino-propoxy)-phenyl]-methanone 
• 141626-57-5 N-(2-butyl-3-(4-(3-(dibutylamino)propoxy)-benzoyl)benzofuran-5-yl)-N-(methylsulfonyl)methanesulfonamide 
• 141626-36-0 dronedarone 
• 141625-93-6 dronedarone hydrochloride 

Relevant articles and documents

2-butyl-3 - (4-substituted propoxy benzoyl) - 5-substituted aminobenzofuran and its application

The invention discloses 2-n-butyl-3-(4-subsitituted propylbenzoyl)-5-substituted amino benzofuran and application thereof. The 2-n-butyl-3-(4-subsitituted propylbenzoyl)-5-substituted amino benzofuran can be used for preparing dronedarone and pharmaceutic

Preparation method of dronedarone hydrochloride key intermediate

The invention relates to a preparation method of a dronedarone hydrochloride key intermediate. The preparation method comprises following steps: 1) 2-butyl-benzofuran-5-ylamine hydrochloride and phthalic anhydride are subjected to reflux reaction under alkaline conditions so as to protect amino groups; and 2) 4-[3-(dibutyl amino) propoxy] benzoic acid is added into Eaton's reagent for stirring reaction, an intermediate 1 is added, temperature is controlled for reaction, a free amine is obtained via treatment, and the free amine and oxalic acid are subjected to salt forming reaction so as to obtain compound IV 5-amino-2-n-butyl-3-[4-(3-n-dibutyl aminopropoxy) benzoyl]benzofuran oxalate. The dronedarone hydrochloride key intermediate is prepared by taking 2-butyl-benzofuran-5-ylamine hydrochloride as the starting raw material; production of the dronedarone free amino is high in selectivity, and high in yield; fewer steps are needed; so that the preparation method is suitable for industrialized production.

Identification and characterization of potential impurities of dronedarone hydrochloride

Six potential process related impurities were detected during the impurity profile study of an antiarrhythmic drug substance, Dronedarone (1). Simple high performance liquid chromatography and liquid chromatography-mass spectrometry methods were used for the detection of these process impurities. Based on the synthesis and spectral data (MS, IR, 1H NMR, 13C NMR, and DEPT), the structures of these impurities were characterized a s 5-amino-3-[4-(3-di-n-butylaminopropoxy)benzoyl]-2-n-butylbenzofuran (impurity I); N-(2-butyl-3-(4-(3-(dibutylamino)propoxy)-benzoyl)benzofuran-5-yl)-N- (methylsulfonyl)-methanesulfonamide (impurity II); N-(2-butyl-3-(4-(3- (dibutylamino)propoxy)benzoyl)benzofuran-5-yl)-1-chloromethanesulfonamide (impurity III); N-{2-propyl-3-[4-(3-dibutylaminopropoxy)benzoyl]benzofuran-5-yl} - methanesulfonamide (impurity IV); N-(2-butyl-3-(4-(3-(dibutylamino)propoxy) benzoyl)benzofuran-5-yl)-formamide (impurity V); and (2-butyl-5-((3- (dibutylamino)propyl)amino)benzofuran-3-yl)(4-(3- (dibutylamino)propoxy)phenyl) methanone (impurity VI). The synthesis and characterization of these impurities are discussed in detail.

An improved scalable route to pure dronedarone hydrochloride

An efficient scalable synthesis for dronedarone hydrochloride (2) via Friedel-Craft acylation of 2-(-2-butyl-1-benzofuran-5-yl)-1H-isoindole-1,3(2H) dione (12) with 4-(3-chloropropoxy) benzoic acid (13) in good yield and high purity has been developed by using Eaton's reagent instead of hazardous and toxic metal halide catalyst like AlCl3 or SnCl4.

Process for obtaining dronedarone

The present invention provides a process for obtaining dronedarone or salts thereof characterized in that in an organic phase comprising one or more non-polar solvents, 5-amino-3-[4-(3-di-n-butylaminopropoxy)benzoyl]-2-n-butyl-benzofuran is reacted with methane sulfonyl chloride without the addition of a base. The invention also provides a process for obtaining intermediates of dronedarone environmentally friendly and industrially viable..

IMPROVED PROCESSES FOR OBTAINING HIGH PURITY OF DRONEDARONE HYDROCHLORIDE

Improved processes for obtaining high purity of Dronedarone hydrochloride (chemically known as N-(2-buty1-3-(4-(3-(dibutylamino)propoxy)benzoyl)-5-benzofuranyl)methanesulfonamide hydrochloride) are provided.

PROCESS FOR OBTAINING DRONEDARONE

The present invention provides a process for obtaining dronedarone or salts thereof characterized in that in an organic phase comprising one or more non-polar solvents, 5-amino-3-[4-(3-di-n-butylaminopropoxy)benzoyl]-2-n-butyl-benzofuran is reacted with methane sulfonyl chloride without the addition of a base. The invention also provides a process for obtaining intermediates of dronedarone environmentally friendly and industrially viable.

PROCESS FOR N-[2-n-BUTYL-3-[4-[3-(DI-n-BUTYLAMINO) PROPOXY]ENZOYL]BENZOFURAN-5-YL]METHANESULFONAMIDE HYDROCHLORIDE

The present invention provides a process for preparing compound of formula (I),

PROCESSES FOR PREPARING DRONEDARONE AND ITS INTERMEDIATES

The invention relates to process for the preparation of benzofuran derivative and intermediates thereof. More particularly, it relates to processes for the preparation of dronedarone or pharmaceutically acceptable acid addition salts thereof in crystalline form. The invention also relates to pharmaceutical compositions that include the dronedarone hydrochloride in crystalline form substantially free from disulfonamide impurity.