- An improved scalable route to pure dronedarone hydrochloride
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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.
- Hivarekar, Raghvendra R.,Deshmukh, Sanjay S.,Tripathy., Narendra K.
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Read Online
- An improved and efficient process for the production of dronedarone hydrochloride, an antiarrhythmia drug
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An improved, high-yielding, and efficient process for the production of dronedarone hydrochloride (1), a class III antiarrhythmia drug for the prevention of cardiac arrhythmias such as atrial fibrillation (AF) is described. The developed process avoids isolation of unstable intermediates at several stages by telescoping the steps upon individual optimization, thereby minimizing the turnaround time of the batch cycle and increasing the throughput. Potential impurities (byproducts) arise during the reaction at various stages, and carry-over impurities from starting materials were controlled selectively by designing reaction conditions and suitable workup procedures, resulting in an increased overall yield from 33% (as per processes reported in the literature) to 66%.
- Mali, Anil C.,Ippar, Sharad S.,Bodke, Mahendra B.,Patil, Nilesh S.,Mathad, Vijayavitthal T.
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Read Online
- Preparation method for dronedarone hydrochloride
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The invention relates to a preparation method for dronedarone hydrochloride. The preparation method includes utilizing 1,4-cyclohexanedione as a raw material to generate dihalogenated-1,4-cyclohexanedione through halogenation reaction with chlorine or bro
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Paragraph 0070-0072; 0077-0085
(2019/03/15)
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- A short synthesis of Dronedarone
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A modification of the Nenitzescu reaction was used to obtain Dronedarone from quinonimine 20 and 1,3-diketone 14 (R = CH2CH2CH2NBu2) in a two-stage process in almost 55% overall yield. Our results represent significant improvement over other state-of-the-art methods as no extra steps for the decoration of the benzofuran core are required.
- Piotrkowska, Barbara,Nerdinger, Sven,Schreiner, Erwin,Seli?, Lovro,Graczyk, Piotr P.
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p. 4330 - 4335
(2018/05/04)
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- Method for synthesizing [...] reach silom
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The invention discloses a dronedarone synthesis method. According to the method, 4-[3-(dibutylamino)propoxy]methyl benzoate, 4-[3-(dibutylamino)propoxy]benzoic acid hydrochloride, 4-[3-(dibutylamino)propoxy]benzoyl chloride, 2-bromohexanoyl chloride, p-methoxyacetanilide, 3-(2-bromohexanoyl chloride)-4-hydroxyacetanilide, N-2-butyl-5-benzofuranamine hydrochloride, N-[(2-butyl-2,3-2H-5-benzofuran)methanesulfonamide], N-2-butyl-3-[4-[3-(dibutylamino)propoxy]benzoyl]-5-benzofuran]-methanesulfonamide and dronedarone are obtained through step-reactions. The dronedarone synthesis method is simple in process, convenient to operate and high in rate of production.
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- PROCESS FOR PREPARING DRONEDARONE AND SALTS THEREOF
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The present disclosure relates to processes for preparing dronedarone or pharmaceutically acceptable salts thereof.
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Page/Page column 13; 14; 15
(2015/03/16)
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- METHOD FOR PREPARING 5-AMINO-BENZOFURAN DERIVATIVES
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The invention relates to a method for preparing 5-amino-benzoyl-benzofuran derivatives having the general formula in which R1 is hydrogen or an alkyl or aryl group and R2 is hydrogen, an alkyl, alkoxy or dialkylaminoalkoxy group. Acc
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Paragraph 0041
(2015/02/19)
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- Identification and characterization of potential impurities of dronedarone hydrochloride
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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.
- Mahender,Saravanan,Sridhar,Chandrashekar,Kumar, L. Jaydeep,Jayashree,Bandichhor, Rakeshwar
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p. 157 - 162
(2014/05/20)
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- A facile and efficient synthesis of dronedarone hydrochloride
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A facile and efficient synthesis of dronedarone hydrochloride starting from commercially available 4- nitrophenol is described. This approach features a tandem-type synthesis of 3-carbonylated benzofuran involving cyclization of 2-ethynylphenol followed by CO2 fixation at the 3-position of the benzofuran ring mediated by potassium carbonate without the addition of any transition metal catalyst.
- Li, Feng,Jin, Chunhua,Zou, Jianwei,Wu, Jun
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p. 1970 - 1972
(2014/09/17)
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- KETOBENZOFURAN DERIVATIVES, METHOD FOR SYNTHESIZING SAME, AND INTERMEDIATES
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The present disclosure relates to ketobenzofuran derivatives of the general formula (I): as well as to a method of synthesizing the same by coupling a quinonimine and an enaminone by a Nenitzescu reaction and to the intermediates of the synthesis thereof.
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Paragraph 0264-0267
(2013/03/26)
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- PREPARATION PROCESS OF DRONEDARONE AND ITS SALTS
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A process is provided for preparing dronedarone or pharmaceutically acceptable salts thereof. The process comprises reacting 5-amino-2-butyl-3-(4-[3-(dibutylamino)propoxy]benzoyl) benzofuran (compound A) with methanesulfonyl chloride without any catalyst
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Paragraph 0050
(2013/04/25)
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- PREPARATION PROCESS OF DRONEDARONE AND ITS SALTS
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A process is provided for preparing dronedarone or pharmaceutically acceptable salts thereof. The process comprises reacting 5-amino-2-butyl-3-(4-[3-(dibutylamino)propoxy]benzoyl)benzofuran (compound A) with methanesulfonyl chloride without any catalyst to provide crude dronedarone hydrochloride, which is purified to afford highly pure product. Then, the dronedarone hydrochloride can be converted to highly pure dronedarone through treatment with an alkaline solvent, the dronedarone can be further converted to other pharmaceutically acceptable salts of dronedarone. In this process, acylation between compound A and methanesulfonyl chloride is carried out successfully and the formation of the dimethylsulfonyl by-product is inhibited.
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Paragraph 0054
(2013/03/28)
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- PROCESS FOR PREPARING AMINOBENZOYLBENZOFURAN DERIVATIVES
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The disclosure relates to a process for preparing 5-aminobenzoylbenzofuran derivatives of formula I: in which R1 and R2 are as defined in the disclosure; by reduction of a 5-nitrobenzofuran derivative of formula II: using a hydrogen
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Paragraph 0043
(2013/07/05)
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- Synthesis of dronedarone and salts thereof
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The present invention relates to a process for preparation of Dronedarone or pharmaceutically acceptable salts thereof. More particularly, the present invention provides a process for preparation of Dronedarone hydrochloride, without the isolation of Dronedarone base.
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Page/Page column 10-11
(2012/03/27)
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- SYNTHESIS OF DRONEDARONE AND SALTS THEREOF
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The present invention relates to a process for preparation of Dronedarone or pharmaceutically acceptable salts thereof. More particularly, the present invention provides a process for preparation of Dronedarone hydrochloride, without the isolation of Dronedarone base.
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Page/Page column 7
(2012/05/07)
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- PROCESS FOR PREPARATION OF N-[2-BUTYL-3-[4-[3-(DIBUTYLAMINO)PROPOXY]BENZOYL]-5-BENZOFURANYL]METHANESULFONAMIDE, ACID ADDITION SALTS AND PRODUCT THEREOF
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The present invention relates to a process for the preparation of highly pure N-[2- butyl-3-[4-[3-(dibutylamino)propoxy]benzoyl]-5- benzofuranyljmethanesulfonamide and pharmaceutically acceptable salts thereof having HPLC purity greater than 99.5%.
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Page/Page column 18
(2012/02/01)
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- PROCESS FOR N-[2-n-BUTYL-3-[4-[3-(DI-n-BUTYLAMINO) PROPOXY]ENZOYL]BENZOFURAN-5-YL]METHANESULFONAMIDE HYDROCHLORIDE
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The present invention provides a process for preparing compound of formula (I),
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Page/Page column 19
(2012/09/22)
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- NOVEL PROCESS FOR THE MANUFACTURE OF DRONEDARONE
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The invention relates to a new process for the preparation of dronedarone and its salts, in particular a synthesis process which allows said compound and its salts to be obtained with good yields, high purity and in an industrially expedient manner; the i
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Page/Page column 3
(2013/02/28)
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- PROCESS FOR OBTAINING DRONEDARONE
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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.
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Page/Page column 14
(2012/05/05)
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- Process for obtaining dronedarone
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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..
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Page/Page column 9
(2012/05/20)
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- PROCESS FOR PREPARING DRONEDARONE
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Disclosed is a process for preparing dronedarone and pharmaceutically acceptable salts thereof. Also disclosed are a novel amorphous form of dronedarone hydrochloride and a preparation process thereof.
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Page/Page column 21-22
(2012/02/02)
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- PROCESSES FOR PREPARING DRONEDARONE AND ITS INTERMEDIATES
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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.
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Page/Page column 36-37
(2012/03/27)
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- IMPROVED PROCESSES FOR OBTAINING HIGH PURITY OF DRONEDARONE HYDROCHLORIDE
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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.
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Page/Page column 3; 13
(2012/12/13)
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- PROCESS FOR THE PREPARATION OF 3-AROYL-5-AMINOBENZOFURAN DERIVATIVES
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The present invention relates to a process for the preparation of 3-aroyl -5- aminobenzofuran derivatives useful as antiarrhythmic drugs which avoids the use of nitro intermediates.
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Page/Page column 47-48
(2012/05/31)
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- NEW PROCESS FOR THE PREPARATION OF DRONEDARONE
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The subject of the present invention is a novel process for the preparation of N- [2-n-butyl-3-{4-[(3-dibutylamino)propoxy]benzoyl}-1-benzofuran-5- yl] methanesulfonamide of formula (I) and the new intermediates of the preparation process.
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- NOVEL PROCESS FOR THE MANUFACTURE OF DRONEDARONE
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The invention relates to a new process for the preparation of dronedarone and its salts, in particular a synthesis process which allows said compound and its salts to be obtained with good yields, high purity and in an industrially expedient manner; the i
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Page/Page column 7-8
(2011/09/30)
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- Crystalline dronedarone salts
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The present invention relates to crystalline dronedarone salts, a process for their preparation as well as pharmaceutical compositions comprising these salts.
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Page/Page column 9
(2011/10/13)
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- Process for preparing dronedarone
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The present invention relates to a process for preparing dronedarone and in particular for preparing an intermediate useful in the preparation of dronedarone. Furthermore, the present invention relates to a process for preparing crystalline dronedarone hydrochloride as well as pharmaceutical compositions comprising this salt.
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Page/Page column 9
(2011/10/13)
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- PREPARATION OF BENZOFURANS AND USE THEREOF AS SYNTHETIC INTERMEDIATES
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The present invention provides several synthetic methods for preparing N-(2-butylbenzofuran-5-yl)-N-(methylsulfonyl)methanesulfonamide, a compound of formula (3), an intermediate in the preparation of Dronedarone. The present invention further provides a process for preparing Dronedarone, comprising the steps of converting 2-butyl-5-bis(methanesulfon)-amidobenzofuran of formula (3) to Dronedarone, wherein the 2-butyl-5-bis(methanesulfon)-amidobenzofuran of formula (3) is prepared by the processes of the present invention.
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Page/Page column 42
(2011/09/15)
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- Methanesulphonamido-benzofuran, preparation method and use thereof as synthesis intermediate
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The invention relates to 2-butyl-5-(methanesulfonamido)benzofuran, its preparation and its use. This compound is a synthesis intermediate, in particular for the preparation of dronedarone.
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Page/Page column 5
(2008/06/13)
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- 2-butyl-3-(4-[3(dibutylamino)propoxy]benzoyl)-5-nitro-benzofuran hydrochloride and preparation thereof
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The invention relates to 2-butyl-3-(4-[3-(dibutylamino)propoxy]benzoyl-5-nitrobenzofuran hydrochloride, to its preparation and to its use as synthetic intermediate, in particular in preparing 2-butyl-3-(4-[3-(dibutylamino)propoxy]benzoyl)-5-nitrobenzofuran, itself an intermediate for dronedarone.
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Page/Page column 6
(2008/06/13)
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- Alkylaminoalkyl derivatives of benzofuran, benzothiophene, indole and indolizine, process for their preparation and compositions containing them
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The subject of the invention is benzofuran, benzothiophene, indole or indolizine compounds of general formula: STR1 in which: Het represents one of the groups: STR2 in which T,T' and T"represent particularly a group: STR3 R and Ra, identical or different, represent X represent --O-- or --S-- Y represents a radical STR4 These compounds are useful as medecines particularly for the treatment of pathological syndroms of the cardio-vascular system.
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