[go: up one dir, main page]

WO2007110884A2 - Procede de preparation de chlorhydrate de fexofenadine anhydre tres pur - Google Patents

Procede de preparation de chlorhydrate de fexofenadine anhydre tres pur Download PDF

Info

Publication number
WO2007110884A2
WO2007110884A2 PCT/IN2007/000127 IN2007000127W WO2007110884A2 WO 2007110884 A2 WO2007110884 A2 WO 2007110884A2 IN 2007000127 W IN2007000127 W IN 2007000127W WO 2007110884 A2 WO2007110884 A2 WO 2007110884A2
Authority
WO
WIPO (PCT)
Prior art keywords
fexofenadine
organic solvent
reaction mixture
process according
hydrochloride
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/IN2007/000127
Other languages
English (en)
Other versions
WO2007110884A3 (fr
Inventor
Lilit Wadhwa
Satyendra Pal Singh
Gajendra Singh
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.)
IND-SWIFT LABORATORIES Ltd
Ind Swift Laboratories Ltd
Original Assignee
IND-SWIFT LABORATORIES Ltd
Ind Swift Laboratories 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 IND-SWIFT LABORATORIES Ltd, Ind Swift Laboratories Ltd filed Critical IND-SWIFT LABORATORIES Ltd
Publication of WO2007110884A2 publication Critical patent/WO2007110884A2/fr
Anticipated expiration legal-status Critical
Publication of WO2007110884A3 publication Critical patent/WO2007110884A3/fr
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
    • C07D211/22—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms

Definitions

  • the present invention relates to a novel process of preparation of highly pure anhydrous Fexofenadine hydrochloride.
  • Fexofenadine hydrochloride namely 4-[4-[4-(hydroxydiphenylmethyl)-l -piperidinyl] l-hydroxybutyl]- ⁇ , ⁇ -dimethylbenzene acetic acid hydrochloride of formula-I is an Hi receptor antagonist and a useful antihistamine drug.
  • terfenadine carboxylic acid metabolite It is a terfenadine carboxylic acid metabolite and lacks the cardiac toxicity associated with terfenadine and may also have greater therapeutic efficacy than the parent drug.
  • Fexofenadine and pharmaceutically acceptable salts were first disclosed in US Patent 4,254, 129 (' 129).
  • fexofenadine can be prepared starting from ethyl ⁇ , ⁇ dimethylphenyl acetate and 4-chlorob ⁇ ityroyl chloride, which are reacted under Freidel-Crafts conditions.
  • Chloride is displaced from the Freidel- Crafts product with ⁇ , ⁇ -diphenyl-4-piperidinemethanol to give 4-[4-[4- (liydroxydiphenylmetliyl)-l-piperidinyl]-l-oxobutyl]- ⁇ 5 ⁇ -dimethylbenzene acetate, which is isolated as its hydrochloride salt.
  • the ketone is then reduced with PtOAH 2 and the ester group is hydrolyzed to yield fexofenadine base.
  • Active pharmaceutical ingredients and their salts are purified and isolated by crystallization from an appropriate solvent during the final step in the synthetic process.
  • a large number of factors can influence crystal nucleation and growth during this process, including the composition, the crystallization medium and the processes used to generate super saturation and promote crystallization.
  • the most notable variables of composition and processing are solvent/solvent combinations, degree of super saturation, pH value, heating rate, cooling rate, etc.
  • Various polymorphs of Fexofenadine hydrochloride have been disclosed in different patents that are referred herein.
  • PCT Publication WO 93/021156 Al relates to the fexofenadine hydrochloride and describes dissolving fexofenadine base in methylene chloride and acidifying with hydogen chloride gas to pH 3. The reaction mass is then concentrated to residue and ether is added and stirred to obtain solid, which is filtered to give fexofenadine hydrochloride.
  • the process leads to the formation of amorphous fexofenadine hydrochloride which has the tendency to pick up moisture and forms lumps on storage, and as such difficult to handle during formulation of tablets and capsules. Further the use of ether is not advisable on commercial scale; hence process is unsuitable for industrial application.
  • PCT Publication WO 95/031437 Al discloses four crystal forms of Fexofenadine hydrochloride which have been designated Forms I-IV.
  • Forms II and IV are hydrates and Forms I and HT are anhydrous. Each form was characterized by its melting point, onset of endotherm in the DSC profile, and PXRD.
  • Forms I-IV Aqueous recrystallization of Form I can be used to produce Form II. Water-minimizing recrystallization or azeotropic distillation of either Form II or Form IV can yield Form I. Crystal digestion of Form III can be used to obtain Form I.
  • PCT Publication WO 00/71124 Al discloses amorphous fexofenadine hydrochloride, which can be prepared by lyophilizing or spray drying a solution of fexofenadine hydrochloride.
  • US patent application no. 2004/004038A1 describes a process for preparing crystalline Fexofenadine hydrochloride Form XVI comprising combining fexofenadine base with a solution of hydrochloric acid and methanol and isopropyl alcohol, followed by evaporation and addition of methanol-heptane to the residue to precipitate Fexofinadine hydrochloride having DSC profile with an endothermic peak at 125°C and an additional peak at 135°C.
  • US patent application no. 2004/0077683 Al discloses a process for the preparation of anhydrous fexofenadine hydrochloride by suspending fexofenadine base in non polar organic solvent and treating with a solvent containing hydrogen chloride.
  • US patent application no. 2005/0165056A1 discloses a process for the preparation of non-hydrated fexofenadine hydrochloride by suspending fexofenadine base in acetonitrile and treating with a solution of hydrogen chloride. There is need to provide an industrially viable process for the preparation of anhydrous Fexofenadine hydrochloride.
  • the present invention provides an industrially advantageous process for the preparation of highly pure anhydrous Fexofenadine hydrochloride, which uses conditions which are convenient to operate on commercial scale and operationally safe.
  • the present invention provides a novel process for preparing anhydrous Fexofenadine hydrochloride from Fexofenadine base of formula-II,
  • Fig. 1 is a PXRD pattern for anhydrous Fexofenadine hydrochloride.
  • Fig. 2 is a DSC thermogram of anhydrous Fexofenadine hydrochloride.
  • the instant invention relates to an improved, simple, efficient and industrially advantageous process for the preparation of highly pure anhydrous Fexofenadine hydrochloride.
  • the present invention relates to a process for the preparation of highly pure crystalline anhydrous fexofenadine hydrochloride from fexofenadine base without isolating any hydrous form of fexofenadine hydrochloride.
  • Fexofenadine base used as a starting material in the present invention can be prepared by any of the methods disclosed in prior art such as US patent 4,254,129, WO 1995/00480 or by the process disclosed in Ind Swift's co-pending application no 2886/ DEL/2005 in India.
  • the present invention provides a process for preparing anhydrous fexofenadine hydrochloride by suspending fexofenadine base in an organic solvent followed by acidification using a solution of hydrogen chloride in alcoholic solvents.
  • the suitable solvent is selected from alcohols, ketones and the like or mixtures thereof.
  • the alcohols can be selected from Ci-C 3 alcohols and ketones can be selected from Ci-C 3 ketones.
  • fexofenadine base is suspended in suitable solvent at ambient temperature and hydrochloride salt preparation is conducted by adjusting the pH of the reaction mixture to 1-4 by addition of alcoholic hydrogen chloride solution.
  • the alcoholic hydrogen chloride solution can be selected from any Ci-C 3 alcohols and preferably isopropa ⁇ ol-hydrogen chloride solution is used.
  • alcohol-hydrogen, chloride solution is prepared by purging dry hydrogen chloride in alcohol by following the methods reported in the prior art.
  • the percentage of hydrogen chloride in alcohol is preferably selected between 20-25%.
  • the reaction mixture becomes a clear solution when hydrochloride salt formation is complete. Thereafter the clear solution is optionally treated with carbon or filtered to remove any foreign particle.
  • the solvent is distilled off under vacuum.
  • Organic solvent is selected from alcohols such as methanol, ethanol, isopropanol or the like and mixture thereof.
  • the reaction mixture is heated at 40-70°C and to this an anti-solvent is added.
  • the anti- solvent is selected from an ester formed from Ci-C 2 alcohol and Cj-C 2 acid and preferably ethyl acetate is used.
  • reaction mass is -heated at 40-70 0 C till complete crystallization. Usually it takes about 2-4 hours for complete crystallization. It is followed by cooling of the reaction mixture to ambient temperature and stirring at this temperature for further 0-2 hours.
  • the precipitate thus forms, can be separated by techniques well known in art such as filtration.
  • the resulting wet precipitate is dried under vacuum at a temperature of about 40-60 0 C to yield the anhydrous Fexofenadine hydrochloride having purity greater than 99.7%.
  • the following examples will illustrate the invention without in any way limiting its scope.
  • Isopropyl alcohol (3.0L) was added to Fexofenadine base (lkg) at ambient temperature. The reaction mass was stirred and pH was adjusted to 2.5-2.6 with isopropyl alcohol-hydrochloric acid (0.40L) at 25-30°C. After checking the clarity of the solution, it was filtered through sparkler and washed with isopropyl alcohol (LOL) which was distilled off completely under vacuum at 35-40 0 C. To the residue, isopropyl alcohol (0.5L) was added followed by addition of ethyl acetate (5.0L) at 35-45°C. The reaction mixture was stirred and heated at 45-50 0 C for about lhour (till complete crystallization).
  • the resulting mixture was cooled to 25-3O 0 C and stirred and centrifuged .
  • the reaction mixture was filtered, washed with ethyl acetate (l.OL) and dried at 40-50 0 C to yield 0.94kg of the title compound having purity 99.76% by high performance liquid chromatography.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Saccharide Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne un procédé innovant et industriellement avantageux permettant de préparer du chlorhydrate de fexofénadine très pur directement à partir de fexofénadine base sans isoler le chlorhydrate de fexofénadine hydraté.
PCT/IN2007/000127 2006-03-29 2007-03-28 Procede de preparation de chlorhydrate de fexofenadine anhydre tres pur Ceased WO2007110884A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN873DE2006 2006-03-29
IN873/DEL/2006 2006-03-29

Publications (2)

Publication Number Publication Date
WO2007110884A2 true WO2007110884A2 (fr) 2007-10-04
WO2007110884A3 WO2007110884A3 (fr) 2009-05-28

Family

ID=38541539

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IN2007/000127 Ceased WO2007110884A2 (fr) 2006-03-29 2007-03-28 Procede de preparation de chlorhydrate de fexofenadine anhydre tres pur

Country Status (1)

Country Link
WO (1) WO2007110884A2 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2012087100A (ja) * 2010-10-21 2012-05-10 Sumitomo Chemical Co Ltd 形態ｉのフェキソフェナジン一塩酸塩の製造方法
CN104072402A (zh) * 2014-07-16 2014-10-01 昆山龙灯瑞迪制药有限公司 一种新结晶形式的盐酸非索非那定化合物及其制备方法

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CH695216A5 (de) * 2001-02-23 2006-01-31 Cilag Ag Verfahren zur Herstellung eines nicht hydratisierten Salzes eines Piperidinderivats und eine so erhältliche neue kristalline Form eines solchen Salzes.
US20040004038A1 (en) * 2002-07-03 2004-01-08 Jfe Engineering Corporation Method and apparatus for treating sludge, and method and apparatus for treating wastewater utilizing the same
US7434282B2 (en) * 2003-05-29 2008-10-14 Star Cushion Products, Inc. Cellular cushions and methods of fabricating

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2012087100A (ja) * 2010-10-21 2012-05-10 Sumitomo Chemical Co Ltd 形態ｉのフェキソフェナジン一塩酸塩の製造方法
CN104072402A (zh) * 2014-07-16 2014-10-01 昆山龙灯瑞迪制药有限公司 一种新结晶形式的盐酸非索非那定化合物及其制备方法

Also Published As

Publication number Publication date
WO2007110884A3 (fr) 2009-05-28

Similar Documents

Publication Publication Date Title
CN101679218B (zh) 晶体米诺环素碱及其制备方法
CN101031548B (zh) N-(4-氟苄基)-n-(1-甲基哌啶-4-基)-n'-(4-(2-甲基丙氧基)-苯基甲基)脲的盐及其制备
AU2007257881B2 (en) Polymorphs of N-hydroxy-3-[4-[[[2-(2-methyl-1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2E-2-propenamide
NO171453B (no) Fremgangsmaate for fremstilling av krystallinsk paroxetin-hydroklorid-hemihydrat
KR20010088795A (ko) ＥｔＯ2Ｃ-ＣＨ2-(Ｒ)Ｃｇｌ-Ａｚｅ-Ｐａｂ-ＯＨ의 결정질형태
US5354760A (en) Crystalline Tiagabine monohydrate, its preparation and use
US10329254B2 (en) Process for the preparation of 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide and intermediates thereof
CN101341122B (zh) 生产高纯度多晶型（ⅰ）盐酸多奈哌齐的方法
MXPA03003459A (es) Base venlafaxina cristalina y polimorfos novedosos de clorhidrato de venlafaxina, procesos para su preparacion.
US20190284197A1 (en) Pharmaceutically acceptable salts and polymorphic forms of hydrocodone benzoic acid enol ester and processes for making same
BG65657B1 (bg) Метод за получаване на амплодипин бензенсулфонат
CN100390145C (zh) 4-[4-[4-(羟基二苯基甲基)-1-哌啶基]-1-羟基丁基]-α,α-二甲基苯乙酸和其盐酸盐的结晶形式
WO2007110884A2 (fr) Procede de preparation de chlorhydrate de fexofenadine anhydre tres pur
AU2001278094A1 (en) Novel crystalline forms of 4-[4-[4-(hydroxydiphenylmethyl)-1-piperindinyl]-1-hydroxybutyl]-alpha, alpha-dimethylbenzene acetic acid and its hydrochloride
CN107531744A (zh) 一种奥贝胆酸的新结晶形式及其制备方法
US7700779B2 (en) Crystalline forms of fexofenadine and its hydrochloride
WO2006003672A1 (fr) Procede de preparation d'amlodipine pure
EP2657232A2 (fr) Processus de purification de composé de benzenesulphonamide
AU2017343384B2 (en) Method for isolation and purification of naltrexone
EP2072510A1 (fr) Forme cristalline d'azélastine
WO2009084030A2 (fr) Procédé amélioré de préparation de la forme iii du chlorhydrate de la 1-benzyl-4-(5,6-diméthoxyindanon-2-yl)méthylpipéridine
EP1858847A1 (fr) Chlorhydrate de donepezil de formule i stable et son procede de preparation et d'utilisation dans des compositions pharmaceutiques
WO2006097341A1 (fr) Procede de preparation du monohydrate d'hydrochlorure de donepezil cristallin
WO2009037718A2 (fr) Procédé de préparation de 3-(2-(diméthylamino)éthyl)-n-méthyl-1h-indole-5-méthanesulfonamide et produit associé
JPH1036350A (ja) ４−ヒドロキシピペリジンの精製方法

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: 07736583

Country of ref document: EP

Kind code of ref document: A2

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 07736583

Country of ref document: EP

Kind code of ref document: A2