EP2595977A1 - Procede de preparation de derives de benzofurane substitues en position 5 - Google Patents

Procede de preparation de derives de benzofurane substitues en position 5

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Publication number
EP2595977A1
EP2595977A1 EP11754896.6A EP11754896A EP2595977A1 EP 2595977 A1 EP2595977 A1 EP 2595977A1 EP 11754896 A EP11754896 A EP 11754896A EP 2595977 A1 EP2595977 A1 EP 2595977A1
Authority
EP
European Patent Office
Prior art keywords
formula
group
compound
alkyl group
branched
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP11754896.6A
Other languages
German (de)
English (en)
French (fr)
Inventor
Fréderic BAILLY
Xavier Bon
Philippe Vayron
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sanofi SA
Original Assignee
Sanofi SA
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sanofi SA filed Critical Sanofi SA
Publication of EP2595977A1 publication Critical patent/EP2595977A1/fr
Withdrawn legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
    • C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
    • C07D307/80—Radicals substituted by oxygen atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
    • C07C251/02—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups
    • C07C251/04—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups having carbon atoms of imino groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C251/10—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups having carbon atoms of imino groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of an unsaturated carbon skeleton
    • C07C251/16—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups having carbon atoms of imino groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of an unsaturated carbon skeleton containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
    • C07C251/32—Oximes
    • C07C251/50—Oximes having oxygen atoms of oxyimino groups bound to carbon atoms of substituted hydrocarbon radicals
    • C07C251/60—Oximes having oxygen atoms of oxyimino groups bound to carbon atoms of substituted hydrocarbon radicals of hydrocarbon radicals substituted by carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/76—Ketones containing a keto group bound to a six-membered aromatic ring

Definitions

  • the present invention relates, in general, to the preparation of 5-substituted benzofuran derivatives.
  • the invention relates to a process for the preparation of 5-substituted benzofuran derivatives of the general formula:
  • R represents a nitro group or ester - COOR '
  • R' represents a hydrogen atom or an alkyl group
  • R1 represents hydrogen or an alkyl group
  • R 2 represents hydrogen, a halogen, a hydroxyl group, haloalkyl, alkyl, alkoxy, dialkylaminoalkoxy or dialkylaminoalkyl.
  • the invention relates to a process for the preparation of compounds of formula (I) in which R represents a nitro group, these compounds of formula (I) are called 5-nitro-benzofuran derivatives of general formula I ':
  • R is nitro
  • R 1 is hydrogen or alkyl
  • R 2 is hydrogen, halogen, alkyl, alkoxy or dialkylaminoalkoxy.
  • the invention relates to a process for the preparation of compounds of formula (I) in which R represents a -COOR 'ester group, these compounds of formula (I) are called 5-substituted benzofuran derivatives of general formula I '':
  • R represents an ester -COOR ' wherein R' represents a hydrogen atom or an alkyl group, R1 represents an alkyl group and R 2 represents hydrogen, a hydroxyl, haloalkyl, dialkylaminoalkoxy or dialkylaminoalkyl group.
  • R 1 represents in particular a linear or branched C 1 -C 8 alkyl group, in particular a linear or branched C 1 -C 4 alkyl group such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl or tert-butyl or a substituted or unsubstituted phenyl group,
  • R 2 is in particular chlorine, bromine or iodine or an alkyl group, linear or branched, in Ci-Os in particular a linear or branched C 1 -C 4 alkyl group such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl or tert-butyl; a linear or branched C 1 -C 6 alkoxy group, especially a linear or branched C 1 -C 4 alkoxy group such as methoxy, ethoxy, n-propoxy, iso-hydroxy, n-butoxy, sec-butoxy or tert-butoxy; a dialkylaminoalkyl group or else a dialkylaminoalkoxy group in which each linear or branched alkyl group is C 1 -C 8 and the linear or branched alkoxy group is C 1 -C 5 in which each linear or branched alkyl group is C 1 -C 4 such
  • R ' is a linear or branched C1-C4 alkyl group such as iso-propyl.
  • R 1 is n-butyl and R 2 is 3- (di-n-butylamino) propoxy.
  • R 1 is n-butyl and R 2 is 3- (di-n-butylamino) propyl.
  • Compound A 2-n-butyl-3- ⁇ 4- [3- (di-n-butylamino) -propoxy] -benzoyl ⁇ -5-nitro-benzofuran (hereinafter referred to as Compound A), a particularly interesting intermediate for preparing dronedarone. According to this method, the following series of reactions can be envisaged:
  • Compound A can be synthesized with overall yields of at least 56% starting from 4-hydroxyacetophenone by a combination of steps using 1- [4- [3- (di-n-butylamino) -propoxy] -phenyl ⁇ -1,3-heptanedione rather than 1- (4-hydroxyphenyl) -1,3-heptanedione.
  • carboxylate commonly known as celivarone
  • its pharmaceutically acceptable salts has been particularly useful especially as antiarrhythmic agent.
  • this synthesis route is convergent and it makes it possible to reduce the number of steps. This path is therefore an economically viable alternative.
  • This route makes it possible in particular to avoid an organometallic coupling step of the type Sonogashira which uses costly reagents and a Friedel-Craft stage which generates large amounts of aluminum salts.
  • the 5-substituted benzofuran derivatives of formula I can be prepared by coupling, in the presence of an acid, the hydroxylamine of formula II:
  • R represents a nitro group or ester COOR '
  • R' have the same meaning as above with a diketone of general formula III:
  • the 5-nitro-benzofuran derivatives of formula I ' can be prepared by coupling in the presence of an acid, O- (4-nitrophenyl) -hydroxylamine of formula II', this compound corresponding to the compound of formula II in which R represents - O2:
  • the benzofuran derivatives of formula I '' can be prepared by coupling, in the presence of an acid, the compound of formula II '', this compound corresponding to the compound of formula II in which R represents COOR ', R' being as previously defined:
  • the oxime is reacted to form a salt such as hydrochloride.
  • the coupling is carried out in the presence of an acid, preferably a weak acid, optionally combined with a strong acid, in general an organic or inorganic acid such as a hydric acid, for example hydrochloric acid.
  • an organic or inorganic acid such as a hydric acid, for example hydrochloric acid.
  • This acid or mixture of acids may be combined, if appropriate, with an organic or inorganic solvent, for example N, N-dimethylformamide, dimethylsulfoxide, an ether such as tetrahydrofuran, diethyl ether or dioxane, or an alcohol such as than methanol or ethanol.
  • the coupling takes place only in an acidic medium that serves both as a reagent and a solvent.
  • the weak acid in question is generally chosen from acids whose boiling point is less than 150 ° C., for example formic acid or, preferably, acetic acid.
  • this weak acid can be used in solution, for example in water or in an organic or inorganic solvent or preferably alone.
  • this weak acid is acetic acid, it preferably corresponds to glacial acetic acid.
  • the coupling reaction is usually carried out at room temperature to form the oxime of formula IV.
  • This oxime is then cyclized by heating in situ that is, in the very midst of his training.
  • the cyclization of this oxime can be carried out ex situ, that is to say separately from its formation medium, and in a solvent such as for example the solvent used during this formation.
  • the process of the invention proceeds at a temperature from room temperature to about 150 ° C.
  • this process is carried out at room temperature when the acid corresponds to a mixture of strong acid and weak acid but at a higher temperature when the acid corresponds only to a weak acid.
  • the reaction temperature will be of the order of 117 ° C-118 ° C.
  • the starting compound of formula II can be obtained according to the following reaction scheme:
  • Hal represents a halogen, for example chlorine or fluorine, which is reacted in the presence of a basic agent such as an alkali metal hydroxide or an alkali metal alkoxide such as sodium tert-butylate or tert-butoxide.
  • potassium butylate in particular potassium tert-butoxide
  • an imidate of formula VI in which R 3 represents a linear or branched C 1 -C 4 alkyl group, for example ethyl, and R 4 represents an alkyl group, linear or branched, C 1 -C 4 such as for example methyl, the reaction taking place at room temperature and, preferably, in a polar solvent such as N, N-dimethylformamide to form an oxime of formula VII in which R 3 and R 4 have the same meaning as before.
  • This oxime is then treated with a strong acid such as hydrochloric acid to form the compound of formula II in the form of an acid addition salt which is then optionally subjected to the action of a strong base such that Sodium hydroxide, to obtain the compound of formula II in free base form.
  • a strong acid such as hydrochloric acid
  • a strong base such that Sodium hydroxide
  • the starting compound of formula II ' can be obtained according to the following reaction scheme:
  • This oxime is then treated with a strong acid such as hydrochloric acid to form the compound of formula II 'in the acid addition salt form which is subjected to then to the action of a strong base such as sodium hydroxide, to obtain the compound of formula II 'in free base form.
  • a strong acid such as hydrochloric acid
  • a strong base such as sodium hydroxide
  • This oxime is then treated with a strong acid such as hydrochloric acid to form the compound of formula II in the form of an acid addition salt which is then optionally subjected to the action of a strong base such that sodium hydroxide, to obtain the compound of formula II '' in free base form.
  • a strong acid such as hydrochloric acid
  • a strong base such that sodium hydroxide
  • the compounds of formula III 'in which R 1 has the same meaning as above and R 2 represents an alkoxy or dialkylaminoalkoxy group are hereinafter referred to as compounds of formula XII. They can be obtained according to the following reaction scheme:
  • R 2 ' represents a linear or branched C 1 -C 5 alkyl group, in particular a linear or branched C 1 -C 4 alkyl group such as methyl, ethyl, n-propyl, isopropyl or n-butyl, and is dry.
  • each linear or branched alkyl group is C 1 -C 5 in which each linear or branched alkyl group is C 1 -C 4 such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl or tert-butyl.
  • the compound of formula X is then coupled with an ester of formula XI in which R 1 and R 3 have the same meaning as above, the coupling taking place in the presence of a strong base such as an alkali metal alkoxide and usually in a solvent polar, for example N-methyl-2-pyrrolidinone to form a diketone of formula XII.
  • a strong base such as an alkali metal alkoxide and usually in a solvent polar, for example N-methyl-2-pyrrolidinone to form a diketone of formula XII.
  • the diketone thus obtained is then isolated directly from its formation medium or, preferably, after treatment with a strong acid such as hydrochloric acid so as to form an acid addition salt, for example the hydrochloride. If necessary, this diketone of formula XII in free base form can be regenerated starting from the acid addition salt thus obtained and this, by treatment of this salt with a basic agent, for example a weak base such as than an alkali metal carbonate or hydrogencarbonate.
  • a basic agent for example a weak base such as than an alkali metal carbonate or hydrogencarbonate.
  • the compounds of formula III '' in which R 1 has the same meaning as above and R 2 represents an alkoxy or dialkylaminoalkoxy group are hereinafter called compounds of formula XII '. They can be obtained according to the following reaction scheme:
  • the compounds of formula XV are then coupled to an amine of formula XVI in which R5 is an alkyl group, especially a C1-C4 alkyl group such as the n-butyl group in the presence of an iodide such as potassium iodide or potassium iodide.
  • an iodide such as potassium iodide or potassium iodide.
  • sodium iodide in solution in an aprotic polar solvent such as methyl isobutyl ketone (MIBK) to give a compound of formula XVII in which R '2 represents a dialkylaminoalkyl group in which the alkyl group represents a C 1 -C 4 alkyl group such as the n-butyl group.
  • the diketone thus obtained is then isolated directly from its formation medium or, preferably, after treatment with a strong acid such as hydrochloric acid so as to form an acid addition salt, for example the hydrochloride. If necessary, this diketone of formula XII in free base form can be regenerated starting from the acid addition salt thus obtained and this, by treatment of this salt with a basic agent, for example a weak base such as than an alkali metal carbonate or hydrogencarbonate.
  • a basic agent for example a weak base such as than an alkali metal carbonate or hydrogencarbonate.
  • Another subject of the invention relates to derivatives of general formula:
  • R 1 ' represents a C 1 -C 4 alkyl group
  • R 1 ' has the same meaning as before and R represents a nitro group or -COOR'
  • R ' has the same meaning as above, these derivatives being, when Y represents the group XX, in the form of the isomer E, d Z isomer or mixtures of these isomers.
  • Another subject of the invention relates to compounds of formula XVIII referred to herein as benzoyloxy derivatives of general formula XVIII ':
  • R 1 ' represents a C 1 -C 4 alkyl group
  • Another subject of the invention relates to compounds of formula XVIII referred to herein as derivatives of general formula XVIII '':
  • R 1 ' represents a C 1 -C 4 alkyl group, or b) a group of the general formula
  • R 1 ', R' has the same meaning as above, these derivatives being, when Y represents the group XX '', in the form of an E isomer, a Z isomer or mixtures of these isomers, this compound corresponding to a compound of formula XX in which R represents a group -COOR ', R' being as defined above.
  • compounds of formula XVIII in which L represents an oxygen atom also form preferred compounds.
  • particularly preferred compounds of the invention are represented by benzoyloxy derivatives of formula XVIII wherein: a) R 2 'is 3- (di-n-butylamino) -propyl, L is a bond and Y is the group of formula XIX wherein R 1 'is n-butyl,
  • R 2 ' represents 3- (di-n-butylamino) -propyl
  • L represents a bond
  • Y represents the group of formula XX in which R 1' represents n-butyl, this compound being in the form of isomer E, d Z isomer or mixture of these isomers.
  • R 2 ' represents 3- (di-n-butylamino) -propyl
  • L represents an oxygen atom
  • Y represents the group of formula XIX in which R 1' represents n-butyl
  • R 2 ' represents 3- (di-n-butylamino) -propyl
  • L represents an oxygen atom
  • Y represents the group of formula XX in which R 1' represents n-butyl, this compound being in the form of an isomer E, isomer Z or a mixture of these isomers.
  • Ri represents n-butyl
  • R 2 ' represents 3- (di-n-butylamino) -propyl and Y represents the group of formula XX' in which R 1 'represents n-butyl, this compound being in the form of E isomer, Z isomer or mixing these isomers.
  • R 2 ' represents 3- (di-n-butylamino) -propyl and Y represents the group of formula XIX in which R 1' represents n-butyl,
  • R 2 ' represents 3- (di-n-butylamino) -propyl and Y represents the group of formula XX' in which R 1 'represents n-butyl, this compound being in the form of E isomer, Z isomer or mixing these isomers.
  • particularly preferred compounds of the invention are represented by the compounds of formula XVIII wherein a) R 2 'represents 3- (di-n-butylamino) -propyl, and Y represents the group of formula XIX in which R 1' represents n-butyl,
  • R 2 ' represents 3- (di-n-butylamino) -propyl and Y represents the group of formula XX''in which
  • R 1 ' represents n-butyl, this compound being in the form of E isomer, Z isomer or a mixture of these isomers.
  • R 2 ' represents 3- (di-n-butylamino) -propyl and Y represents the group of formula XIX in which R 1' represents n-butyl,
  • R 2 ' represents 3- (di-n-butylamino) -propyl and Y represents the group of formula XX''in which R 1' represents n-butyl, this compound being in the form of E isomer, of Z isomer or mixing these isomers.
  • the organic phases are combined and washed with a mixture of 200 ml of water, 2.24 ml of 90% acetic acid and 3.75 g of sodium chloride and then twice with an aqueous solution of sodium chloride. . We wear then the organic phase to dry to obtain the desired compound X.
  • the organic phase is successively washed with water, a solution of hydrochloric acid, water, an aqueous solution of potassium carbonate and an aqueous solution of sodium chloride.
  • the aqueous phases are treated with sodium hydroxide and counter-extracted with dichloromethane.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Cardiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Furan Compounds (AREA)
EP11754896.6A 2010-07-21 2011-07-20 Procede de preparation de derives de benzofurane substitues en position 5 Withdrawn EP2595977A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR1055951A FR2963006B1 (fr) 2010-07-21 2010-07-21 Procede de preparation de derives de nitro-benzofurane
PCT/FR2011/051751 WO2012010802A1 (fr) 2010-07-21 2011-07-20 Procede de preparation de derives de benzofurane substitues en position 5

Publications (1)

Publication Number Publication Date
EP2595977A1 true EP2595977A1 (fr) 2013-05-29

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EP11754896.6A Withdrawn EP2595977A1 (fr) 2010-07-21 2011-07-20 Procede de preparation de derives de benzofurane substitues en position 5

Country Status (13)

Country Link
US (1) US8748636B2 (enrdf_load_stackoverflow)
EP (1) EP2595977A1 (enrdf_load_stackoverflow)
JP (1) JP2013533267A (enrdf_load_stackoverflow)
KR (1) KR20130094305A (enrdf_load_stackoverflow)
CN (1) CN103221401A (enrdf_load_stackoverflow)
AU (1) AU2011281435A1 (enrdf_load_stackoverflow)
BR (1) BR112013001365A2 (enrdf_load_stackoverflow)
CA (1) CA2805868A1 (enrdf_load_stackoverflow)
FR (1) FR2963006B1 (enrdf_load_stackoverflow)
MX (1) MX2013000845A (enrdf_load_stackoverflow)
RU (1) RU2013107600A (enrdf_load_stackoverflow)
SG (1) SG187565A1 (enrdf_load_stackoverflow)
WO (1) WO2012010802A1 (enrdf_load_stackoverflow)

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
HUP0900759A2 (en) 2009-12-08 2011-11-28 Sanofi Aventis Novel process for producing dronedarone
HUP1000010A2 (en) 2010-01-08 2011-11-28 Sanofi Sa Process for producing dronedarone
FR2958290B1 (fr) 2010-03-30 2012-10-19 Sanofi Aventis Procede de preparation de derives de sulfonamido-benzofurane
HUP1000330A2 (en) 2010-06-18 2011-12-28 Sanofi Sa Process for the preparation of dronedarone and the novel intermediates
FR2962731B1 (fr) 2010-07-19 2012-08-17 Sanofi Aventis Procede de preparation de derives d'amino-benzoyl-benzofurane
HUP1100167A2 (en) 2011-03-29 2012-11-28 Sanofi Sa Process for preparation of dronedarone by mesylation
HUP1100165A2 (en) 2011-03-29 2012-12-28 Sanofi Sa Process for preparation of dronedarone by n-butylation
FR2983198B1 (fr) 2011-11-29 2013-11-15 Sanofi Sa Procede de preparation de derives de 5-amino-benzoyl-benzofurane
EP2617718A1 (en) 2012-01-20 2013-07-24 Sanofi Process for preparation of dronedarone by the use of dibutylaminopropanol reagent
WO2013121235A2 (en) 2012-02-13 2013-08-22 Sanofi Process for preparation of dronedarone by removal of hydroxyl group
US9249119B2 (en) 2012-02-14 2016-02-02 Sanofi Process for the preparation of dronedarone by oxidation of a sulphenyl group
WO2013124745A1 (en) 2012-02-22 2013-08-29 Sanofi Process for preparation of dronedarone by oxidation of a hydroxyl group
WO2013178337A1 (en) 2012-05-31 2013-12-05 Sanofi Process for preparation of dronedarone by grignard reaction
CN109384754B (zh) * 2017-08-14 2020-06-09 新发药业有限公司 一种盐酸决奈达隆的制备方法

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FR2962731B1 (fr) 2010-07-19 2012-08-17 Sanofi Aventis Procede de preparation de derives d'amino-benzoyl-benzofurane
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HUP1100167A2 (en) 2011-03-29 2012-11-28 Sanofi Sa Process for preparation of dronedarone by mesylation
HUP1100165A2 (en) 2011-03-29 2012-12-28 Sanofi Sa Process for preparation of dronedarone by n-butylation

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Also Published As

Publication number Publication date
FR2963006B1 (fr) 2013-03-15
MX2013000845A (es) 2013-02-11
US20130165674A1 (en) 2013-06-27
RU2013107600A (ru) 2014-08-27
JP2013533267A (ja) 2013-08-22
WO2012010802A1 (fr) 2012-01-26
AU2011281435A1 (en) 2013-02-07
US8748636B2 (en) 2014-06-10
CN103221401A (zh) 2013-07-24
KR20130094305A (ko) 2013-08-23
FR2963006A1 (fr) 2012-01-27
CA2805868A1 (fr) 2012-01-26
BR112013001365A2 (pt) 2016-05-17
SG187565A1 (en) 2013-03-28

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