[go: up one dir, main page]

WO2012004658A2 - Procédé de préparation du n-[2-butyl-3-[4-[3-(dibutylamino)propoxy]benzoyl]-5-benzofuranyl]méthanesulfonamide, sels d'addition acide et produit de celui-ci - Google Patents

Procédé de préparation du n-[2-butyl-3-[4-[3-(dibutylamino)propoxy]benzoyl]-5-benzofuranyl]méthanesulfonamide, sels d'addition acide et produit de celui-ci Download PDF

Info

Publication number
WO2012004658A2
WO2012004658A2 PCT/IB2011/001593 IB2011001593W WO2012004658A2 WO 2012004658 A2 WO2012004658 A2 WO 2012004658A2 IB 2011001593 W IB2011001593 W IB 2011001593W WO 2012004658 A2 WO2012004658 A2 WO 2012004658A2
Authority
WO
WIPO (PCT)
Prior art keywords
butyl
propoxy
benzoyl
dibutylamino
benzofuranyl
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.)
Ceased
Application number
PCT/IB2011/001593
Other languages
English (en)
Other versions
WO2012004658A3 (fr
WO2012004658A8 (fr
Inventor
Rajiv Kumar
Vijay Tambe
Sanjay Patil
Kishor Chavan
Syed Shawkat Naim
Ramesh Dandala
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.)
FRICHEM PRIVATE Ltd
Original Assignee
FRICHEM PRIVATE Ltd
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 FRICHEM PRIVATE Ltd filed Critical FRICHEM PRIVATE Ltd
Publication of WO2012004658A2 publication Critical patent/WO2012004658A2/fr
Publication of WO2012004658A8 publication Critical patent/WO2012004658A8/fr
Publication of WO2012004658A3 publication Critical patent/WO2012004658A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

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

Definitions

  • the present invention relates to a novel process for the preparing N-[2-butyl-3-[4- [3-(dibutylamino)propoxy]benzoyl]-5-benzofuranyl]methanesulfonamide and pharmaceutically acceptable salts thereof and its intermediates.
  • Dronedarone SR 33589
  • Multaq® for the treatment of arrhythmia which is available as tablet in strength of 400 mg.
  • Dronedarone which is chemically known as N-[2-butyl-3-[4-[3- (dibutylamino)propoxy]benzoyl]-5-benzofuranyl]methanesulfonamide, having a formula (I) was first disclosed in US 5,223,510 (US'510).
  • US' 510 disclose several processes for preparation of the dronedarone along with its therapeutic use.
  • this method when applied to the preparation of dronedarone hydrochloride comprise steps of,
  • US'510 describes the use of catalyst such as platinum or palladium oxide, zinc in a hydrochloric acid medium or tin in a hydrochloric acid medium for hydrogenating of nitro group of the derivative into amino group.
  • catalyst such as platinum or palladium oxide
  • zinc in a hydrochloric acid medium or tin in a hydrochloric acid medium for hydrogenating of nitro group of the derivative into amino group.
  • the same reaction is depicted in the form of example 1(f) in US'510 which discloses process for preparing 5-Amino-2-butyl-3-[4-(3-dibutylamino-propoxy)benzoyl]- 2-(n-butyl)-benzofuran from 2-(n-butyl)-3-[4--(3-dibutylamino- propoxy)benzoyl]-5-nitrobenzofuran by means of platinum oxide under pressure of 3.4 atmosphere.
  • Example 3 of US' 510 discloses a process for preparing sulfonamide salt of 5- amino-2-butyl-3-[4-aminoalkoxy] benzoylbenzofuran by condensation of solution of methanesulfonyl chloride in dichloromethane with 5-amino-3-[4-(3- di-(n-butyl)amino-propoxy)benzoyl]-2-(n-butyl)benzofuran in presence of triethylamine to get dronedarone base which is further purified by means of chromatography on a column of silica.
  • the pure dronedarone base obtained in preceding step is crystallized by hexane followed by addition of hydrogen chloride in ether to solution of pure dronedarone in ethyl acetate to get dronedarone hydrochloride which is recrystalized in acetone with purity of about 98.0%.
  • Noel Fino et. al. in US 6,828,448 discloses process for preparing dronedarone hydrochloride comprising catalytic hydrogenation of 2-butyl-5-nitrobenzofuran by means of platinum derivative such as platinum oxide or an ammonium formate/palladized charcoal system to get 5-amino-2-butylbenzofuran which is further treated with methanesulfonyl chloride or methanesulfonic anhydride in presence of acid acceptor.
  • platinum derivative such as platinum oxide or an ammonium formate/palladized charcoal system
  • It is yet another object of the invention is to obtain stable, pure acid addition salts of dronedarone having high purity. It is yet another object of the invention to obtain stable acid addition salts of 2- butyl-5-amino-3-[4-(3-(dibutylamino)propoxy]benzoyl]]benzofuran in crystalline and amorphous forms.
  • a process for preparing highly pure N-[2-butyl-3-[4-[3- (dibutylamino)propoxy]benzoyl]-5-benzofuranyl]methanesulfonamide hydrohalide having purity greater than 99.5% comprising hydrogenating 2- butyl-3-[4-[3-(dibutylamino)propoxy]benzoyl]-5-nitrobenzofuran by means of a catalyst in presence of a hydrogen transfer reagent to obtain 5-amino-2-butyl-3- [4-[3-(dibutylamino)propoxy]benzoyl]benzofuran optionally converted into its acid addition salts followed by condensing the 5-amino-2-butyl-3-[4-[3- (dibutylamino) propoxy]benzoyl]benzofuran or its acid addition salts with methane sulphonyl halide in presence of water and/
  • the process for preparing highly pure N-[2- butyl-3-[4-(3-(di-n- butylamino)propoxy)benzoyl]-5-benzofuranyl]methanesulfonamide hydrohalide optionally employing a base during condensation.
  • an improved process for preparing 5-amino-2-butyl-3-[4-[3- (dibutylamino)propoxy]benzoyl]benzofuran by hydrogenating 2-butyl-3-[4-[3- (dibutylamino)propoxy]benzoyl]-5-nitrobenzofuran in presence of catalyst and hydrogen transfer reagent where 2-butyl-5-amino-3-[4-[3- (dibutylamino)propoxy]benzoyl]-benzofuran is optionally converted into its acid addition salts.
  • an improved process for preparing N-[2-butyl-3-[4-[3- (dibutylamino)propoxy]benzoyl]-5-benzofuranyl]methanesulfonamide or its acid addition salts comprising condensing 2-butyl-5-amino-3-[4-(3- (dibutylamino)propoxy]benzoyl]]benzofuran or its acid addition salts with methane sulphonyl halide in presence of water and/or organic solvent and optionally a base.
  • a crystalline N-[2-butyl-3-[4-[3-(dibutylamino)propoxy]benzoyl]-5- benzofuranyl]methane sulfonamide free base characterized by PXRD having peaks at 5.52, 8.21, 10.91, 13.62, 15.52, 16.33, 16.60, 17.74, 19.04, 19.91, 21.78, 23.79, 24.52, 25.04 and 30.05 ⁇ 0.2 2 ⁇ values as depicted in figure 7.
  • an amorphous N-[2-butyl-3-[4-[3-(dibutylamino)propoxy]benzoyl]-5- benzofuranyljmethane sulfonamide hydrochloride salt there is provided an amorphous N-[2-butyl-3-[4-[3-(dibutylamino)propoxy]benzoyl]-5- benzofuranyljmethane sulfonamide hydrochloride salt.
  • a process for preparing amorphous N-[2-butyl-3-[4-[3- (dibutylamino)propoxy]benzoyl]-5-benzofuranyl]methanesulfonamide hydrohalide wherein the process comprising dissolving crystalline N-[2-butyl-3- [4-[3-(dibutylamino)propoxy]benzoyl]-5-benzofuranyl]methanesulfonamide. hydrochloride/ hydrobromide in a solvent followed by isolating an amorphous solid.
  • a crystalline oxalate salt of 2-butyl-5-amino-3-[4-(3- (dibutylamino)propoxy]benzoyl]] benzofuran characterized by PXRD having peaks at 7.45, 8.15, 10.00, 10.66, 13.06, 15.27, 17.55, 20.07, 21.43, 22.45, 23.42, 23.76, 25.09, 26.18 and 30.06 ⁇ 0.2 2 ⁇ values as shown in figure 6
  • FIG. 1 is a characteristic powder x-ray diffraction pattern of crystalline N-[2- butyl-3-[4-[3-(dibutylamino)propoxy]benzoyl]-5- benzofuranyl]methanesulfonamide hydrochloride of the present invention.
  • FIG. 2 is a characteristic powder x-ray diffraction pattern of amorphous N-[2- butyl-3-[4-[3-(dibutylamino)propoxy]benzoyl]-5- benzofuranyl]methanesulfonamide hydrochloride of the present invention.
  • FIG. 3 is a characteristic powder x-ray diffraction pattern of amorphous N-[2- butyl-3-[4-[3-(dibutylamino)propoxy]benzoyl]-5- benzofuranyl]methanesulfonamide hydrobromide of the present invention.
  • FIG. 4 is a characteristic powder x-ray diffraction pattern of crystalline N-[2- butyl-3-[4-[3-(dibutylamino)propoxy]benzoyl]-5- benzofuranyl]methanesulfonamide hydrobromide of the present invention.
  • FIG. 5 is a characteristic powder x-ray diffraction pattern of amorphous form of hydrochloride salt of compound of 2-butyl-5-amino-3-[4-(3- (dibutylamino)propoxy]benzoyl]]benzofuran of the present invention.
  • FIG. 6 is a characteristic powder x-ray diffraction pattern of crystalline form of oxalate salt of compound of 2-butyl-5-amino-3-[4-(3- (dibutylamino)propoxy]benzoyl]] benzofuran of the present invention.
  • FIG. 7 is a characteristic powder x-ray diffraction pattern of crystalline form of N- [2-butyl-3 -[4- [3 -(dibutylamino)propoxy]benzoy 1] -5 - benzofuranyl]methanesulfonamide free base of the present invention.
  • the present invention discloses highly pure N-[2-butyl-3-[4-[3- (dibutylamino)propoxy]benzoyl]-5-benzofuranyl]methanesulfonamide
  • (dronaderone) hydrohalide having purity greater than 99.5% with disulfonamide and DRN-amino impurity less than 0.15% and process for preparing the same thereof.
  • the present invention discloses acid addition salts of the same and polymorphic form thereof.
  • the hydrohalide is preferably hydrochloride and hydrobromide.
  • the process for preparing highly pure N-[2-butyl-3- [4-[3-(dibutylamino)propoxy]benzoyl]-5-benzofuranyl]methanesulfonamide hydrohalide having purity greater than 99.5% comprises the following steps: a) hydrogenating 2-butyl-3-[4-[3-(dibutylamino)propoxy]benzoyl]-5- nitrobenzofuran (formula III ) by means of a catalyst in presence of a hydrogen transfer reagent to obtain 5-amino-2-butyl-3-[4-[3-
  • the salts of dronedarone are obtained directly from condensation stage, exclusive of isolation of dronedarone base which reduces the reaction time and provides the product in optimum yield with HPLC purity of >99.0%.
  • the disclosed embodiment of the present invention deals with the highly pure dronedarone hydrochloride with the purity of >99% in optimum yield where the impurities are restricted to less than 0.15%.
  • the impurities mentioned herein are given below as sulfonamide (formula IV) impurity and DRN-amino impurity II.
  • the first embodiment is the hydrogenation of the compound of formula III in presence of catalyst and suitable hydrogen transfer catalyst.
  • a suitable catalyst employed are selected from group comprising platinum or palladium charcoal system, palladium, or Raney Ni, zinc dust, mixture of zinc and hydrochloride acid, stannous chloride, mixture of tin and hydrochloric acid, rhodium and platinum.
  • the hydrogen transfer reagents are selected from the group consisting of but not limited to hydrogen gas, aliphatic alcohol, alkali metal and amine esters of fatty acids exemplified by sodium acetate, ammonium formate, sodium format and potassium format preferably ammonium formate and sodium formate or mixtures thereof.
  • the molar ratio of compound of 2-butyl-3-[4-[3-(dibutylamino)propoxy]benzoyl]-5- nitrobenzofuran (formula III) to the hydrogen transfer reagents can be 1 :1 to 1 : 5, preferably 1 : 2 to 1 :4, more preferably 1: 2.5.
  • the reaction is usually carried out in an solvent and solvents used during the hydrogenation reaction are selected from the group consisting of but not limited to ether such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, 2- methyl tetrahydrofuran; organic acid such as formic acid, acetic acid; alcohol such as methanol, ethanol, isopropyl alcohol, butanol, propanol; or mixture thereof.
  • ether such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, 2- methyl tetrahydrofuran
  • organic acid such as formic acid, acetic acid
  • alcohol such as methanol, ethanol, isopropyl alcohol, butanol, propanol; or mixture thereof.
  • the reaction temperature is usually within range between 20°C to reflux temperature of the solvent used in the reaction.
  • the above hydrogenation reaction is carried out at atmospheric pressure as well as at high pressure depending on the hydrogen transfer reagents used along with catalyst for the reaction. Alternatively, the reaction can also be carried out in inert atmosphere.
  • the compound of formula II obtained from hydrogenation step can optionally be isolated as such i.e. free DRN-amino base or as its acid addition salts wherein acid addition salts include oxalate, tartarate, fumarate, hydrochloride, hydrobromide and the like.
  • acid addition salts include oxalate, tartarate, fumarate, hydrochloride, hydrobromide and the like.
  • These salts are prepared by reacting compound of formula II with an acid in a solvent followed by the addition of anti solvents.
  • the solvent used herein is selected from the group comprising of alcohol such as methanol, ethanol, propanol, iso-propanol, butanol, iso-butanol and the like.
  • the anti-solvent used herein is selected from the group consisting of but not limited to ether such as diethyl ether, diisopropyl ether and the like.
  • the obtained acid addition salts are having the purity of >98.5% by HPLC and further characterized as crystalline as well as amorphous form.
  • sulfonylation reaction of compound of formula II or its acid addition salt to obtain dronedarone or its acid addition salt.
  • the solvent used for sulfonylation step herein is selected from the group consisting of water or organic solvents.
  • the organic solvent used herein is selected from the group consisting of but not limited to alcohol such as methanol, ethanol; ketone such as acetone, methyl isobutyl ketone, methyl ethyl ketone; nitrile such as acetonitrile, propionitrile; dimethylformamide, dimethylsulfoxide, ether such as tetrahydrofuran, dioxane; ester such as ethyl acetate, n-butyl acetate, isopropyl acetate; aromatic hydrocarbon such as toluene, xylene; chlorinated hydrocarbon such as chloroform, carbon tetrachloride, methylene dichloride or mixtures thereof.
  • alcohol such as methanol, ethanol
  • ketone such as acetone, methyl isobutyl ketone, methyl ethyl ketone
  • nitrile such as acetonitrile, propionitrile
  • the reaction temperature is usually about -10°C - 60°C, preferably about 20- 40°C, more preferably about 35-45°C.
  • the molar ratio of methane sulphonyl halide to the compound of formula II is in the ratio of 0.7-2.0.
  • base is optionally added during condensation reaction in the molar ratio of 0.5 to 1.5 with respect to compound II where the base is selected from the group consisting of but not limited to organic or inorganic base.
  • Organic base used herein is selected from the group consisting of but not limited to triethyl amine, diisopropyl amine, diisopropyl ethyl amine, N-methylpyrrolidone, pyridine, morphine and the like.
  • Inorganic base used herein is selected from the group consisting of but not limited to alkali metal, alkaline earth metal hydroxide, carbonate, hydroxy carbonate such as sodium hydroxide, sodium carbonate, sodium hydroxycarbonate, potassium hydroxide, potassium carbonate, potassium hydroxycarbonate and the like.
  • the methane sulfonyl halide used herein is selected from the group consisting of methane sulfonyl chloride or bromide.
  • the product obtained from the above sulfonylation reaction is in the form of either hydrochloride or hydrobromide salt.
  • the dronedarone hydrochloride salt or hydrobromide salt thus obtained is in crystalline form which is optionally purified further to get HPLC purity of >99.5% with disulfonamide impurity as ⁇ 0.15% and DRN-amino impurity as ⁇ 0.15%.
  • the purification process of dronedarone acid addition salt wherein acid addition salts of dronedarone is dissolved in mixture of acetone and water in the molar ratio of 1:0.03 followed by cooling to isolate crystalline acid addition salts of dronedarone with desired purity.
  • a dronedarone free base with HPLC purity of >99.5% is isolated.
  • the pure dronedarone free base as solid can be prepared by reacting acid addition salts of dronedarone with suitable base in presence of solvent.
  • the base used herein is selected from the group consisting of organic base such as triethyl amine, diisopropyl amine, diisopropyl ethyl amine and the like or inorganic base such as ammonia, alkali metal, alkaline earth metal hydroxide such as sodium hydroxide, potassium hydroxide; carbonate such as sodium carbonate, potassium carbonate; hydroxy carbonate such as sodium hydroxycarbonate, potassium hydroxy carbonate and the like.
  • the solvent used herein is water immiscible solvent selected from the group consisting of but not limited to ester such as ethyl acetate, butyl acetate, propyl acetate; halogenated solvents such as methylene dichloride, trichloromethane; hydrocarbon solvent such as toluene, xylene; hydrocarbons such as hexane, heptane, cyclohexane, pentane; alcohol such as n- butanol, isopropanol and the like or mixture thereof.
  • the dronedarone free base can be further converted to its acid addition salts by reaction it with acid in presence of solvent.
  • the acid used herein is selected from the group consisting of but not limited to oxalic acid, malic acid, tartaric acid, fumaric acid, succinic acid, acetic acid, salicylic acid, phthalic acid, hydrochloric acid, hydrobromic and sulfuric acid preferably hydrochloride salt or hydrobromide salt.
  • the solvent used herein is selected from the group consisting of but not limited to ester such as ethyl acetate, propyl acetate, butyl acetate.
  • a crystalline N- [2-butyl-3-[4-[3-(dibutylamino)propoxy]benzoyl]-5- benzofuranyl]methanesulfonamide free base characterized by PXRD having peaks at 5.52, 8.21, 10.91, 13.62, 15.52, 16.33, 16.60, 17.74, 19.04, 19.91, 21.78, 23.79, 24.52, 25.04 and 30.05 ⁇ 0.2 20 values as depicted in figure 7.
  • a crystalline N-[2-butyl-3-[4-[3-(dibutylamino)propoxy]benzoyl]-5- benzofuranyl]methanesulfonamide hydrobromide salt characterized by PXRD having peaks at 7.65, 7.75, 8.08, 11.87, 13.11, 13.70, 15.54, 15.64, 16.20, 20.19, 20.73, 21.02, 21.23, 21.62, 24.08, 25.95, 27.39 and 28.20 ⁇ 0.2 20 values as shown in figure 4.
  • an amorphous N-[2-butyl-3-[4-[3-(dibutylamino)propoxy]benzoyl]-5- benzofuranyljmethanesulfon amide hydrochloride salt is characterized by PXRD as shown in figure 2.
  • a process for preparing the amorphous N-[2-butyl-3-[4-[3- (dibutylamino)propoxy]benzoyl]-5-benzofuranyl]methanesulfonamide hydrohalide comprising dissolving crystalline N-[2-butyl-3- [4-[3-(dibutylamino)propoxy]benzoyl]-5-benzofuranyl]methanesulfonamide hydrochloride/ hydrobromide in a solvent followed by isolating an amorphous solid.
  • the isolation is performed by filtration or by addition of anti-solvent selected from the group comprising ether such as diethyl ether, diisopropyl ether and the like.
  • the solvent employed is selected from the group comprising of chlorinated solvents such as methylene dichloride, trichloromethane or mixtures thereof in the temperature range of 0 to 70°C, preferably 15-60°C, more preferably 25-50°C.
  • the obtained solution is further evaporated to get the residue which can further isolated as solid either by means of filtration or by addition of solvent selected from the group comprising of ether such as , diethyl ether, diisopropyl ether and the like.
  • the purity of the compound obtained herewith is >99.5% by HPLC.
  • a crystalline oxalate salt of 2- butyl-5-amino-3-[4-[3-(dibutylamino)propoxy]benzoyl]benzofuran characterized by PXRD having peaks at 7.45, 8.15, 10.00, 10.66, 13.06, 15.27, 17.55, 20.07, 21.43, 22.45, 23.42, 23.76, 25.09, 26.18 and 30.06 ⁇ 0.2 2 ⁇ values as shown in figure 6.
  • PXRD peaks at 7.45, 8.15, 10.00, 10.66, 13.06, 15.27, 17.55, 20.07, 21.43, 22.45, 23.42, 23.76, 25.09, 26.18 and 30.06 ⁇ 0.2 2 ⁇ values as shown in figure 6.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Furan Compounds (AREA)

Abstract

La présente invention concerne un procédé pour la préparation de N-[2-butyl-3-[4-[3-(dibutylamino)propoxy]benzoyl]-5-benzofuranyl]méthanesulfonamide et de sels pharmaceutiquement acceptables de celui-ci ayant une pureté CLHP supérieure à 99,5 %.
PCT/IB2011/001593 2010-07-09 2011-07-08 Procédé de préparation du n-[2-butyl-3-[4-[3-(dibutylamino)propoxy]benzoyl]-5-benzofuranyl]méthanesulfonamide, sels d'addition acide et produit de celui-ci Ceased WO2012004658A2 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
IN1979MU2010 2010-07-09
IN1979/MUM/2010 2010-07-09
IN2716/MUM/2010 2010-09-27
IN2716MU2010 2010-09-27

Publications (3)

Publication Number Publication Date
WO2012004658A2 true WO2012004658A2 (fr) 2012-01-12
WO2012004658A8 WO2012004658A8 (fr) 2012-03-15
WO2012004658A3 WO2012004658A3 (fr) 2012-05-18

Family

ID=44759725

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2011/001593 Ceased WO2012004658A2 (fr) 2010-07-09 2011-07-08 Procédé de préparation du n-[2-butyl-3-[4-[3-(dibutylamino)propoxy]benzoyl]-5-benzofuranyl]méthanesulfonamide, sels d'addition acide et produit de celui-ci

Country Status (1)

Country Link
WO (1) WO2012004658A2 (fr)

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012032545A1 (fr) * 2010-09-08 2012-03-15 Cadila Healthcare Limited Procédé pour préparer un dérivé de benzofurane et des produits intermédiaires de celui-ci
WO2012131408A1 (fr) * 2011-03-29 2012-10-04 Sanofi Procédé de préparation de dronédarone par mésylation
WO2012120544A3 (fr) * 2011-03-10 2012-11-01 Sun Pharmaceutical Industries Ltd. Procédé de préparation d'hydrochlorure de n-[2-n-butyl-3-[4-[3-(di-n-butylamino) propoxy]enzoyl]benzofuran-5-yl]méthanesulfonamide
WO2014203058A1 (fr) * 2013-06-17 2014-12-24 Aurobindo Pharma Limited Procédé amélioré de préparation de composé benzofurane
US9174959B2 (en) 2011-03-29 2015-11-03 Sanofi Process for preparation of dronedarone by N-butylation
US9174958B2 (en) 2010-06-18 2015-11-03 Sanofi Process for the preparation of dronedarone
US9221777B2 (en) 2012-01-20 2015-12-29 Sanofi Process for preparation of dronedarone by the use of dibutylaminopropanol reagent
US9221778B2 (en) 2012-02-13 2015-12-29 Sanofi Process for preparation of dronedarone by removal of hydroxyl group
US9238636B2 (en) 2012-05-31 2016-01-19 Sanofi Process for preparation of dronedarone by Grignard reaction
US9249119B2 (en) 2012-02-14 2016-02-02 Sanofi Process for the preparation of dronedarone by oxidation of a sulphenyl group
US9334254B2 (en) 2010-03-30 2016-05-10 Sanofi Process for preparing sulfonamidobenzofuran derivatives
US9382223B2 (en) 2012-02-22 2016-07-05 Sanofi Process for preparation of dronedarone by oxidation of a hydroxyl group
US9499507B2 (en) 2011-11-29 2016-11-22 Sanofi Method for preparing 5-amino-benzoyl-benzofuran derivatives

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5223510A (en) 1990-08-06 1993-06-29 Sanofi Alkylaminoalkyl derivatives of benzofuran, benzothiophene, indole and indolizine, process for their preparation and compositions containing them
US6828448B2 (en) 2000-12-11 2004-12-07 Sanofi-Synthelabo Methanesulphonamido-benzofuran, preparation method and use thereof as synthesis intermediate
US6846936B2 (en) 2000-12-11 2005-01-25 Sanofi-Synthelabo 2-butyl-3-(4-[3(dibutylamino)propoxy]benzoyl)-5-nitro-benzofuran hydrochloride and preparation thereof

Family Cites Families (3)

* 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
EP2371808A1 (fr) * 2010-03-08 2011-10-05 Ratiopharm GmbH Procédé de préparation de dronédarone
EP2371824A1 (fr) * 2010-03-08 2011-10-05 Ratiopharm GmbH Sels de dronédarone cristallines

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5223510A (en) 1990-08-06 1993-06-29 Sanofi Alkylaminoalkyl derivatives of benzofuran, benzothiophene, indole and indolizine, process for their preparation and compositions containing them
US6828448B2 (en) 2000-12-11 2004-12-07 Sanofi-Synthelabo Methanesulphonamido-benzofuran, preparation method and use thereof as synthesis intermediate
US6846936B2 (en) 2000-12-11 2005-01-25 Sanofi-Synthelabo 2-butyl-3-(4-[3(dibutylamino)propoxy]benzoyl)-5-nitro-benzofuran hydrochloride and preparation thereof

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9334254B2 (en) 2010-03-30 2016-05-10 Sanofi Process for preparing sulfonamidobenzofuran derivatives
US9174958B2 (en) 2010-06-18 2015-11-03 Sanofi Process for the preparation of dronedarone
WO2012032545A1 (fr) * 2010-09-08 2012-03-15 Cadila Healthcare Limited Procédé pour préparer un dérivé de benzofurane et des produits intermédiaires de celui-ci
WO2012120544A3 (fr) * 2011-03-10 2012-11-01 Sun Pharmaceutical Industries Ltd. Procédé de préparation d'hydrochlorure de n-[2-n-butyl-3-[4-[3-(di-n-butylamino) propoxy]enzoyl]benzofuran-5-yl]méthanesulfonamide
WO2012131408A1 (fr) * 2011-03-29 2012-10-04 Sanofi Procédé de préparation de dronédarone par mésylation
US9174959B2 (en) 2011-03-29 2015-11-03 Sanofi Process for preparation of dronedarone by N-butylation
US9193703B2 (en) 2011-03-29 2015-11-24 Sanofi Process for preparation of dronedarone by mesylation
US9611242B2 (en) 2011-03-29 2017-04-04 Sanofi Process for preparation of dronedarone by N-butylation
US9499507B2 (en) 2011-11-29 2016-11-22 Sanofi Method for preparing 5-amino-benzoyl-benzofuran derivatives
US9708281B2 (en) 2012-01-20 2017-07-18 Sanofi Process for preparation of dronedarone by the use of dibutylaminopropanol reagent
US9221777B2 (en) 2012-01-20 2015-12-29 Sanofi Process for preparation of dronedarone by the use of dibutylaminopropanol reagent
US9221778B2 (en) 2012-02-13 2015-12-29 Sanofi Process for preparation of dronedarone by removal of hydroxyl group
US9701654B2 (en) 2012-02-13 2017-07-11 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
US9382223B2 (en) 2012-02-22 2016-07-05 Sanofi Process for preparation of dronedarone by oxidation of a hydroxyl group
US9238636B2 (en) 2012-05-31 2016-01-19 Sanofi Process for preparation of dronedarone by Grignard reaction
WO2014203058A1 (fr) * 2013-06-17 2014-12-24 Aurobindo Pharma Limited Procédé amélioré de préparation de composé benzofurane

Also Published As

Publication number Publication date
WO2012004658A3 (fr) 2012-05-18
WO2012004658A8 (fr) 2012-03-15

Similar Documents

Publication Publication Date Title
WO2012004658A2 (fr) Procédé de préparation du n-[2-butyl-3-[4-[3-(dibutylamino)propoxy]benzoyl]-5-benzofuranyl]méthanesulfonamide, sels d'addition acide et produit de celui-ci
KR101440257B1 (ko) 약학적 활성 화합물의 제조에 사용되는 중간체의 제조 방법
CN102770420B (zh) 制备决奈达隆的新方法
JP2004515536A (ja) ２−ブチル−３−（４−［３−（ジブチルアミノ）プロポキシ］ベンゾイル）−５−ニトロベンゾフラン塩酸塩およびその製造
CN104520275B (zh) 用于制备整合酶抑制剂的方法和中间产物
HK1043130B (zh) 制备5-氰基2-苯并[c]呋喃酮的方法
US6680386B2 (en) Process for preparing 2-(4-chlorobenzoylamino)-3-[2 (1H)-quinolinon-4-yl] propionic acid
RU2621725C2 (ru) Способ получения 1-([1,3]диоксолан-4-илметил)-1н-пиразол-3-иламина
US12037343B2 (en) Process for the preparation of sodium (2r,5s,13ar)-7,9-dioxo-10-((2,4,6,-trifluorobenzyl)carbamoyl)-2,3,4,5,7,9,13,13A-octahydro-2,5-methanopyrido[1′,2′:4,5]pyrazino[2,1-B] [1,3] oxazepin-8-olate and its polymorphic form
JP2003506425A (ja) ナプロキセンのニトロキシアルキルエステルの製造法
EP1846385B1 (fr) Synthese exo-selective d'analogues d'himbacine
US20110087042A1 (en) Crystalline oxybutynin and process for preparing the same
US8044196B2 (en) Process for producing pure form of 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine
RU2402532C2 (ru) Способ получения монтелукаста и соединения для его осуществления
WO2016115962A1 (fr) Procédé de préparation d'intermédiaire de nébivolol et procédé de préparation de nébivolol
KR960005955B1 (ko) 벤조[b]티오펜-5-일 유도체 및 이의 제조방법
KR102748251B1 (ko) 리나글립틴 및 이의 염의 제조를 위한 중간체 및 방법
JP2005501056A (ja) ５−置換イソベンゾフランの製造方法
US20050192338A1 (en) Process for the preparation of Ropinirole
WO2007132990A1 (fr) Procédé de préparation de glycidylphthalimide chirale de haute pureté optique,
US6531594B2 (en) Process for producing 1H-3-aminopyrrolidine and derivatives thereof
US7989645B2 (en) Process for preparation of citalopram and enantiomers
JPH06340623A (ja) ベンジルコハク酸誘導体の製造方法およびその製造中間体
CN110467612B (zh) 一种前列腺素d2受体抑制剂化合物的简便制备方法
JP2002284761A (ja) 光学活性３−アミノピロリジン−２，５−ジオン誘導体および光学活性３−アミノピロリジン誘導体の製造方法

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 11764849

Country of ref document: EP

Kind code of ref document: A2

NENP Non-entry into the national phase in:

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 11764849

Country of ref document: EP

Kind code of ref document: A2