[go: up one dir, main page]

WO2008137512A2 - Procédé de préparation de prégabaline - Google Patents

Procédé de préparation de prégabaline Download PDF

Info

Publication number
WO2008137512A2
WO2008137512A2 PCT/US2008/062164 US2008062164W WO2008137512A2 WO 2008137512 A2 WO2008137512 A2 WO 2008137512A2 US 2008062164 W US2008062164 W US 2008062164W WO 2008137512 A2 WO2008137512 A2 WO 2008137512A2
Authority
WO
WIPO (PCT)
Prior art keywords
solvent
reaction mixture
methyl
hofmann
ethyl amine
Prior art date
Application number
PCT/US2008/062164
Other languages
English (en)
Other versions
WO2008137512A3 (fr
Inventor
Srinivas Reddy Gade
Narasimha Murthy Harikeerthi
Ravindhranath Tagore Amirisetty
Vijaya Wardhan Chitta
Venkateswarlu Muvva
Original Assignee
Dr. Reddy's Laboratories Ltd.
Dr. Reddy's Laboratories, Inc.
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 Dr. Reddy's Laboratories Ltd., Dr. Reddy's Laboratories, Inc. filed Critical Dr. Reddy's Laboratories Ltd.
Publication of WO2008137512A2 publication Critical patent/WO2008137512A2/fr
Publication of WO2008137512A3 publication Critical patent/WO2008137512A3/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/04—Formation of amino groups in compounds containing carboxyl groups

Definitions

  • the present application relates to a process for the preparation of (S)-3- (amino methyl)-5-methylhexanoic acid.
  • the adopted name of (S)-3-(amino methyl)-5-methylhexanoic acid is
  • Pregabalin and is structurally represented by Formula I.
  • Pregabalin is an anticonvulsant agent and is used in the treatment of central neuropathic (nerve) pain.
  • Pregabalin is commercially available under the brand name Lyrica in the United States of America.
  • U.S. Patent No. 6197819 describes process for the preparation of (S)-3- (amino methyl)-5-methylhexanoic acid wherein the desired stereochemical configuration is achieved using 4-methyl valeric acid as the starting material and chiral oxazolidinone as chiral auxiliary.
  • U.S. Patent No. 5616793 describes a process for making (S)-3-(amino methyl)-5-methylhexanoic acid.
  • the process involves the resolution of racemic 3- (carbamoyl methyl)-5- methyl hexanoic acid using (R)-(+)-phenyl ethyl amine as chiral base.
  • the (R)-(+)-phenyl ethyl amine salt of (R)-3- (carbamoyl methyl)-5- methyl hexanoic acid is hydrolyzed with an acid to liberate (R)-3- (carbamoyl methyl)-5- methyl hexanoic acid.
  • the resulting R-enantiomer is subjected to
  • the present application relates to a process for the preparation of
  • the present invention relates to a process of producing Pregabalin comprising the steps of subjecting the combination of (R)-3-(carbamoyl methyl)-5-methyl hexanoic acid, (R)-(+)-phenyl ethyl amine salt, a base and an aqueous solvent (a reaction mixture) to a
  • the present invention relates to a process of producing Pregabalin comprising the steps of creating a reaction mixture by combining (R)-3-(carbamoyl methyl)-5-methyl hexanoic acid, (R)-(+)-phenyl ethyl amine salt with an aqueous solution and a base; subjecting the combination to a Hofmann reaction; and recovering Pregabalin.
  • the process in another embodiment, comprises some or all of the following steps: (a) combining 3-(carbamoyl methyl)-5-methyl hexanoic acid with (R)-(+)-phenyl ethyl amine to afford (R)-3-(carbamoyl methyl)-5-methyl hexanoic acid, (R)- (+)-phenyl ethyl amine salt;
  • Pregabalin can then be isolated and/or collected.
  • aqueous solution herein refers to water or water in combination with other solvents.
  • Figure 1 provides the powder X-ray diffraction (PXRD) pattern for Pregabalin produced by subjecting a mixture of (R)-3-(carbamoyl methyl)-5- methyl hexanoic acid, (R)-(+)-phenyl ethyl amine salt, a base and an aqueous solvent to a Hofmann reaction.
  • PXRD powder X-ray diffraction
  • ingredients in addition to those recited in the claim, but only if the additional ingredients do not materially alter the basic and novel characteristics of the claimed invention. Preferably, such additives will not be present at all or only in trace amounts. However, it may be possible to include up to about 10% by weight of materials that could materially alter the basic and novel characteristics of the invention as long as the utility of the compounds (as opposed to the degree of utility) is maintained. All ranges recited herein include the endpoints, including those that recite a range "between" two values.
  • shifts in peak positions or the relative intensities of one or more peaks of a pattern can occur because of, without limitation: the equipment used, the sample preparation protocol, preferred packing and orientations, the radiation source, operator error, method and length of data collection, and the like.
  • those of ordinary skill in the art should be able to compare the figures herein with a pattern generated of an unknown form of, in this case, Pregabalin, and confirm its identity as one of the forms disclosed and claimed herein. The same holds true for other techniques which may be reported herein.
  • pure When a molecule or other material is identified herein as “pure”, it generally means, unless specified otherwise, that the material is about 99% pure or more. In general, this refers to purity with regard to unwanted residual solvents, reaction byproducts, impurities and unreacted starting materials. In the case of stereoisomers, “pure” also means 99% of one enantiomer or diastereomer, as appropriate. “Substantially” pure means, the same as “pure” except that the lower limit is about 95% pure or more and likewise, “essentially” pure means the same as “pure” except that the lower limit is about 90% pure.
  • the present application provides a process for the preparation of Pregabalin.
  • the process can comprise some or all of the following steps: (a) reacting 3-(carbamoyl methyl)-5- methyl hexanoic acid of formula Il with
  • Optionally separating (R)-(+)-phenyl ethyl amine comes next. Thereafter (whether or not the optional separation step is employed), the combination of the compound, base and solvent are further combined with at least one Hofmann reagent and a Hofmann reaction is undertaken to form Pregabalin.
  • the combination with the Hofmann reagent can also be accomplishes where the reagent is generated within the reaction mixture.
  • the enantiomers of 3-(carbamoyl methyl)-5- methyl hexanoic acid may be separated by selective crystallization of diastereomeric salt with chiral base such as (R)-(+)-phenyl ethyl amine. Racemic 3-(carbamoyl methyl)-5- methyl hexanoic acid is combined with (R)-(+)-phenyl ethyl amine in a solvent or mixture of solvents.
  • the process of the instant application further comprises combining the (R)-3- (carbamoyl methyl)-5- methyl hexanoic acid, (R)-(+)-phenyl ethyl amine salt, as made using the process steps described above or otherwise, with an aqueous solution or solvent and a base.
  • the aqueous solution refers to water and water miscible solvents and mixtures of either with water immiscible solvent(s).
  • the aqueous part of the reaction mixture may be mixed with a fresh lot of water immiscible solvent.
  • the resulting biphasic reaction mixture may be subjected to Hofmann reaction.
  • the reaction mixture containing aq. layer and water immiscible solvent may be treated with Hofmann reagent. After the completion of the reaction, the water immiscible solvent may be separated to proceed for further work up.
  • the base employed in the process of the present application may be alkali metal hydroxide.
  • the alkali metal hydroxide includes sodium hydroxide, potassium hydroxide and lithium hydroxide.
  • Pregabalin obtained by the above said process is characterized by its Powder X-Ray Diffraction (PXRD) pattern having characteristic peaks at diffraction angles 2 theta of about 9.4, 12.2, 18.2, 18.3, 19.0, 19.7, 23.2, 23.5, 24.6, 26.9,
  • PXRD Powder X-Ray Diffraction
  • the crystalline Pregabalin obtained by the process of the present application also has PXRD pattern substantially according to Figure
  • the PXRD data reported herein was obtained using CuKoc radiation, having the wavelength 1.541 A and on a Bruker AXS D8 Advance Powder X-ray
  • EXAMPLE 1 PREPARATION OF(R)-3-(CARBAMOYL METHYL)-5-METHYL HEXANOIC ACID, (R)-(+)-PHENYLETHYL AMINE SALT A mixture of 3-(carbamoyl methyl)-5-methylhexanoic acid (50 g), (R)-(+)- phenyl ethylamine (23.6 g), chloroform (580 ml) and ethanol (12 ml) was heated to 55°C for 30 minutes. The reaction mixture was cooled to 30-35 0 C and stirred for 30 minutes. The separated solid was filtered, washed with chloroform (90 ml) and dried at 5O 0 C under vacuum for 6 hours to afford 33.0 g of the title compound.
  • reaction mixture was cooled to 35-40 0 C and aqueous hydrochloric acid (31.4 g, 30%) was added.
  • the reaction mixture was heated to 90°C and stirred for 3 hours.
  • the reaction mixture was cooled to 0-5°C and stirred for 2 hours.
  • the separated solid was filtered, washed with water (20 ml) and dried at 6O 0 C for 6 hours to afford 15 g of the title compound.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Peptides Or Proteins (AREA)

Abstract

L'invention concerne un procédé de préparation de prégabaline, qui comprend la réaction de l'acide R-3-(carbamoyl méthyl)-5-méthyl hexanoïque, du sel de (R)-(+)-phényléthylamine et d'une base dans une solution aqueuse, et éventuellement la séparation de (R)-(+)-phényléthylamine et le traitement ultérieur du mélange réactionnel avec un réactif de Hofmann.
PCT/US2008/062164 2007-05-03 2008-05-01 Procédé de préparation de prégabaline WO2008137512A2 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
IN935CH2007 2007-05-03
IN935/CHE/2007 2007-05-03
US1252907P 2007-12-10 2007-12-10
US61/012,529 2007-12-10

Publications (2)

Publication Number Publication Date
WO2008137512A2 true WO2008137512A2 (fr) 2008-11-13
WO2008137512A3 WO2008137512A3 (fr) 2009-03-19

Family

ID=39811525

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2008/062164 WO2008137512A2 (fr) 2007-05-03 2008-05-01 Procédé de préparation de prégabaline

Country Status (1)

Country Link
WO (1) WO2008137512A2 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009147528A1 (fr) * 2008-06-02 2009-12-10 Actavis Group Ptc Ehf Procédé perfectionné de préparation de prégabaline
WO2014072785A2 (fr) 2012-11-07 2014-05-15 Hikal Limited Procédé de préparation de prégabaline

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5616793A (en) * 1995-06-02 1997-04-01 Warner-Lambert Company Methods of making (S)-3-(aminomethyl)-5-methylhexanoic acid

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009147528A1 (fr) * 2008-06-02 2009-12-10 Actavis Group Ptc Ehf Procédé perfectionné de préparation de prégabaline
US20110245536A1 (en) * 2008-06-02 2011-10-06 Actavis Group Ptc Ehf Process for preparing pregabalin
WO2014072785A2 (fr) 2012-11-07 2014-05-15 Hikal Limited Procédé de préparation de prégabaline

Also Published As

Publication number Publication date
WO2008137512A3 (fr) 2009-03-19

Similar Documents

Publication Publication Date Title
JP5188501B2 (ja) モンテルカストおよびそのアミン塩類の精製方法
US8198485B2 (en) Resolution of 4,5-dimethoxy-1-(methylaminomenthyl)-benzocyclobutane
WO2007119114A2 (fr) Procédé perfectionné de synthèse et de préeparations de sels de duloxétine
WO2016092478A1 (fr) Procédé de préparation de luliconazole
WO2014167428A2 (fr) 4-(3-(4-cyano-3-(trifluorométhyl)phényl)-5,5-diméthyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-n-méthylbenzamide amorphe
US7858812B2 (en) Process for isolation of desired isomers of nebivolol intermediates
HUP0303496A2 (hu) Kristályos venlafaxin bázis és a venlafaxin hidroklorid új polimorf módosulatai, eljárások ezek előállítására
SE441358B (sv) Sett att framstella 2-substituerad-trans-5-aryl-2,3,4,4a,5,9b-hexahydro-1h-pyrido-(4,3-b)indoler
EP3558954B1 (fr) Procédé amélioré pour la fabrication de r-6-hydroxy-8-[1-hydroxy-2-[2- (4-méthoxyphényl)-1,1-diméthyléthylaminoéthyl]-2h-1,4-benzoxazin-3 (4h)-one chlorhydrate
JP2011516519A (ja) アルガトロバン一水和物の多形体及びその合成方法
US7728173B2 (en) Processes for preparing venlafaxine and venlafaxine hydrochloride of form I
WO2008137512A2 (fr) Procédé de préparation de prégabaline
EP1177166B1 (fr) Processus de preparation de (1r,2s,4r) -(-)-2- (2'- n,n-dimethylamino -ethoxy) -2- phenyle -1,7,7-tri- methyle -bicyclo 2.2.1 heptane et sels d'addition acides pharmaceutiquement acceptables de ceux-ci
JP4874122B2 (ja) トルテロジンを得るための方法
US20130085304A1 (en) Processes for preparation of polymorphic forms of lacosamide
WO2009047797A2 (fr) Procédé de préparation d'un dérivé du perhydroisoindole
EP3230258B1 (fr) Procédé pour la préparation de (1s,2r)-milnacipran
WO2007080470A2 (fr) Procede de purification de levetiracetame
US7173153B2 (en) Sertraline hydrochloride form II and methods for the preparation thereof
WO2006090265A2 (fr) Procedes de preparation de levetiracetam, son intermediaire et utilisation de levetiracetam dans des compositions pharmaceutiques
WO2008107797A2 (fr) Polymorphes de chlorhydrate de lercanidipine et procédé amélioré de préparation d'acétoacétate de 1,1,n-triméthyl-n-(3,3-diphénylpropyl)-2-aminoéthyle
WO2015104602A2 (fr) Procédé de préparation d'anagliptine et de ses intermédiaires
WO2013090161A1 (fr) Synthèse stéréosélective du tapendatol et de ses sels
KR20210090225A (ko) 에피나코나졸의 제조 방법
US11572333B2 (en) Processes for the production of isomerically pure or enriched cis-clomiphene

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: 08747298

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: 08747298

Country of ref document: EP

Kind code of ref document: A2