WO2006136866A1 - Process for enantiomeric separation of zopiclone - Google Patents
Process for enantiomeric separation of zopiclone Download PDFInfo
- Publication number
- WO2006136866A1 WO2006136866A1 PCT/GB2006/050166 GB2006050166W WO2006136866A1 WO 2006136866 A1 WO2006136866 A1 WO 2006136866A1 GB 2006050166 W GB2006050166 W GB 2006050166W WO 2006136866 A1 WO2006136866 A1 WO 2006136866A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- disorder
- eszopiclone
- anxiety
- alcohol
- salt
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
Definitions
- the present invention relates to a process for the separation of the dextrorotatory isomer of 6-(5-chloro-2-pyridyl)-5[(4-methyl-l-piperazinyl)-carbonyloxy]-7-oxo-6,7- dihydro-5H-pyrrolo-[3,4b]-pyrazine (zopiclone) or eszopiclone from the racemic mixture.
- Zopiclone chemically named ( ⁇ ) of 6-(5-chloro-2-pyridinyl)-6,7-dihydro-7-oxo-5H- pyrrolo-[3,4b]-pyrazin-5-yl-4-methylpiperazine-l-caboxylate, of Formula (I) is a non-benzodiazepine hypnotic.
- Zopiclone and its optically pure enantiomers are useful in the treatment of diseases and conditions including epilepsy, anxiety, aggressive behavior, muscle tension, behavioral disorders, depression, schizophrenia and endocrine disorders.
- Racemic zopiclone has been used to improve sleep in adults and geriatric patients with several types of sleep disorders including situational, transient and chronic insomnia of primary and secondary nature.
- Zopiclone binds at or near ben2odiazepine receptor complexes. These complexes are located both within the central nervous system and peripherally, and contain macromolecular complexes, which comprise benzodiazepine and GABA binding sites.
- Enantiomers have the same solubility profile and cannot be readily separated by simple recrystallisation, but diastereoisomers generally have different solubilities in some selected solvents.
- the present invention is advantageous in terms of reduction in total number of steps for separation of enantiomers, this being a single step separation. There is no derivatisation being carried out and thus no degradation of zopiclone occurs. The separated optically active enantiomer is pure; therefore no purification step is required.
- Simulated moving bed is a method in process chromatography that enables substance mixtures to be continuously separated and extracted in two fractions.
- each partial fraction can be separated into a further fraction - up to binary substance mixtures.
- the SMB process is set up in advance for a two-component mixture. Following this, both substances can be immediately extracted in pure form.
- a multi-column continuous process or a simulated moving bed process is used for the separation of eszopiclone, which comprises a chiral stationary phase and mobile phase.
- the mobile phase used is selected from alcohols, organic solvents or mixtures thereof.
- Alcohol for the mobile phase is selected from methanol, ethanol, propanol, isopropanol or mixtures thereof.
- Organic solvents are selected from acetonitrile and hexane.
- Organic amine co-solvents such as dimethylamine can be used in the mobile phase.
- Mixtures of alcohol and organic solvents can be used as mobile phase.
- a mixture of acetonitrile and methanol can be used or a mixture of hexane and isopropanol can be used as a mobile phase.
- the temperature employed for the present process is at 15-40 0 C. While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention. The details of the invention, its objects and advantages are explained hereunder in greater detail in relation to non-limiting exemplary illustrations.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA002612763A CA2612763A1 (en) | 2005-06-21 | 2006-06-21 | Process for enantiomeric separation of zopiclone |
EP06755797A EP1919912A1 (en) | 2005-06-21 | 2006-06-21 | Process for enantiomeric separation of zopiclone |
AU2006260686A AU2006260686A1 (en) | 2005-06-21 | 2006-06-21 | Process for enantiomeric separation of zopiclone |
US11/961,673 US20080182848A1 (en) | 2005-06-21 | 2007-12-20 | Novel Process |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IN728MU2005 | 2005-06-21 | ||
IN728/MUM/2005 | 2005-06-21 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/961,673 Continuation US20080182848A1 (en) | 2005-06-21 | 2007-12-20 | Novel Process |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2006136866A1 true WO2006136866A1 (en) | 2006-12-28 |
Family
ID=36954270
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/GB2006/050166 WO2006136866A1 (en) | 2005-06-21 | 2006-06-21 | Process for enantiomeric separation of zopiclone |
Country Status (5)
Country | Link |
---|---|
US (1) | US20080182848A1 (en) |
EP (1) | EP1919912A1 (en) |
AU (1) | AU2006260686A1 (en) |
CA (1) | CA2612763A1 (en) |
WO (1) | WO2006136866A1 (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2058313A2 (en) * | 2007-10-11 | 2009-05-13 | Apotecnia , S.A. | Process for synthesis and purification of anhydrous crystalline S-zopiclone |
US7772396B2 (en) | 2007-08-02 | 2010-08-10 | Esteve Quimica, S.A. Avda. Mare de deu de Monsterrat | Process for the resolution of zopiclone and intermediate compounds |
EP2345655A1 (en) | 2010-01-05 | 2011-07-20 | LEK Pharmaceuticals d.d. | A process for racemisation of 6-(5-chloropyridin-2-yl)-7-(4-methyl-1-piperazinyl)carbonyloxy-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20070270590A1 (en) * | 2006-04-20 | 2007-11-22 | Marioara Mendelovici | Methods for preparing eszopiclone crystalline form a, substantially pure eszopiclone and optically enriched eszopiclone |
US20080015197A1 (en) * | 2006-06-26 | 2008-01-17 | Alex Mainfeld | Process for the preparatrion of zopiclone |
WO2008094690A2 (en) * | 2007-01-31 | 2008-08-07 | Teva Pharmaceutical Industries Ltd. | Methods for preparing eszopiclone |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5641404A (en) * | 1993-08-27 | 1997-06-24 | The Dow Chemical Company | Process for the separation of enantiomers |
US5786357A (en) * | 1991-12-02 | 1998-07-28 | Sepracor Inc. | Methods and compositions for treating sleep disorders, convulsive seizures and other disorders using optically pure (+) zopiclone |
US5889180A (en) * | 1997-11-10 | 1999-03-30 | Uop Llc | Use of small pore silicas as a support for a chiral stationary phase |
US6319926B1 (en) * | 1991-01-17 | 2001-11-20 | Sepracor Inc. | Optically active 5H-pyrrolo[3, 4-B]pyrazine derivative, its preparation and pharmaceutical compositions containing it |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6339086B1 (en) * | 1999-05-14 | 2002-01-15 | Swpracor, Inc. | Methods of making and using N-desmethylzopiclone |
ES2203319B1 (en) * | 2002-04-03 | 2005-03-01 | Universidad De Oviedo | NEW OPTICALLY ACTIVE CARBONATES AS INTERMEDIATES IN THE SYNTHESIS OF (+) - ZOPICLONA. |
-
2006
- 2006-06-21 AU AU2006260686A patent/AU2006260686A1/en not_active Abandoned
- 2006-06-21 WO PCT/GB2006/050166 patent/WO2006136866A1/en not_active Application Discontinuation
- 2006-06-21 CA CA002612763A patent/CA2612763A1/en not_active Abandoned
- 2006-06-21 EP EP06755797A patent/EP1919912A1/en not_active Withdrawn
-
2007
- 2007-12-20 US US11/961,673 patent/US20080182848A1/en not_active Abandoned
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6319926B1 (en) * | 1991-01-17 | 2001-11-20 | Sepracor Inc. | Optically active 5H-pyrrolo[3, 4-B]pyrazine derivative, its preparation and pharmaceutical compositions containing it |
US5786357A (en) * | 1991-12-02 | 1998-07-28 | Sepracor Inc. | Methods and compositions for treating sleep disorders, convulsive seizures and other disorders using optically pure (+) zopiclone |
US5641404A (en) * | 1993-08-27 | 1997-06-24 | The Dow Chemical Company | Process for the separation of enantiomers |
US5889180A (en) * | 1997-11-10 | 1999-03-30 | Uop Llc | Use of small pore silicas as a support for a chiral stationary phase |
Non-Patent Citations (5)
Title |
---|
C. FERNANDEZ ET. AL.: "Determination of the Enantiomers of Zopiclone and its Two Chiral etabolites in Urine Using an Automated Coupled Achiral-Chiral Chromatographic System.", JOURNAL OF CHROMATOGRAPHY, BIOMEDICAL APPLICATIONS, vol. 617, 1993, pages 271 - 278, XP002399168 * |
C. FERNANDEZ ET. AL.: "Determination of Zopiclone Enantiomers in Plasma by Liquid Chromatography Using a Chiral Cellulose Carbamate Column", JOURNAL OF CHROMATOGRAPHY, vol. 572, 1991, pages 195 - 202, XP009072353 * |
E. MANNAERT ET. AL.: "Semi-Preparative Chiral resolution of Zoplicone and N-Desmethylzoplicone", JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, vol. 14, 1996, pages 1367 - 1370, XP002399169 * |
N. BARGMANN-LEYDER ET. AL.: "A Comparison of LC and SFC for Cellulose- and Amylose-Derived Chiral Stationary Phases.", CHIRALITY, vol. 7, 1995, pages 311 - 325, XP009072351 * |
S. PIPERAKI ET. AL.: "Enantiomeric Separation of Zopiclone, its Metabolites and Products of Degradation onan beta-Cyclodextrin Bonded Phase.", JOURNAL OF CHROMATOGRAPHY, A, vol. 729, 1996, pages 19 - 28, XP004039158 * |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7772396B2 (en) | 2007-08-02 | 2010-08-10 | Esteve Quimica, S.A. Avda. Mare de deu de Monsterrat | Process for the resolution of zopiclone and intermediate compounds |
EP2058313A2 (en) * | 2007-10-11 | 2009-05-13 | Apotecnia , S.A. | Process for synthesis and purification of anhydrous crystalline S-zopiclone |
EP2058313A3 (en) * | 2007-10-11 | 2009-06-24 | Apotecnia , S.A. | Process for synthesis and purification of anhydrous crystalline S-zopiclone |
ES2324136A1 (en) * | 2007-10-11 | 2009-07-30 | Apotecnia S.A. | Process for synthesis and purification of anhydrous crystalline S-zopiclone |
EP2345655A1 (en) | 2010-01-05 | 2011-07-20 | LEK Pharmaceuticals d.d. | A process for racemisation of 6-(5-chloropyridin-2-yl)-7-(4-methyl-1-piperazinyl)carbonyloxy-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine |
Also Published As
Publication number | Publication date |
---|---|
EP1919912A1 (en) | 2008-05-14 |
US20080182848A1 (en) | 2008-07-31 |
CA2612763A1 (en) | 2006-12-28 |
AU2006260686A1 (en) | 2006-12-28 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20080182848A1 (en) | Novel Process | |
Fogassy et al. | Optical resolution methods | |
Kamal et al. | Chemoenzymatic synthesis2 of both enantiomers of fluoxetine, tomoxetine and nisoxetine: lipase-catalyzed resolution of 3-aryl-3-hydroxypropanenitriles | |
JP4503594B2 (en) | Process for producing chiral beta amino acid derivatives by asymmetric hydrogenation | |
Spivey et al. | New atropisomeric biaryl derivatives of 4-aminopyridine—identification of an improved nucleophilic catalyst for asymmetric acylation of sec-alcohols | |
WO1995008636A1 (en) | Racemate cleavage of primary and secondary amines by enzyme-catalysed acylation | |
US20080096939A1 (en) | Process For Preparation Of Pramipexole By Chiral Chromatography | |
Lin et al. | Overview of chirality and chiral drugs | |
CN100457746C (en) | Method for the preparation of escitalopram | |
AU2006215955A1 (en) | Process for making trans-1-((1R, 3S)-6-chloro-3-phenylindan-1-yl)-3, 3-dimethylpiperazine | |
Hill et al. | Development of a large-scale route to glecaprevir: synthesis of the side chain and final assembly | |
Gong et al. | Diastereoselective Friedel–Crafts reaction of α-trifluoromethyl imines derived from chiral amines | |
Fernández et al. | Enantioselective synthesis of cis-α-substituted cycloalkanols and trans-cycloalkyl amines thereof | |
Mittendorf et al. | Efficient asymmetric synthesis of β-amino acid BAY 10-8888/PLD-118, a novel antifungal for the treatment of yeast infections | |
Gutman et al. | Stereo-and regioselectivity in asymmetric synthesis of α-amino substituted benzocyclic compounds | |
KR102598202B1 (en) | Separation of the enantiomers of 3-ethylbicyclo[3.2.0]hept-3-en-6-one | |
US20040176637A1 (en) | Process for preparation of 2-chlorophenylglycine derivatives and enantiomerically separation | |
Kang et al. | A highly stereoselective and efficient synthesis of enantiomerically pure sitagliptin | |
KR20140107250A (en) | Optical resolution method for bicyclic compound using asymmetric catalyst | |
CN113045468A (en) | Preparation method of brivaracetam intermediate | |
Collina et al. | Enantioselective chromatography and absolute configuration of N, N‐dimethyl‐3‐(naphthalen‐2‐yl)‐butan‐1‐amines: Potential sigma1 ligands | |
KR20180073113A (en) | Racemization method of enantiomers of N-[4-(1-aminoethyl)-2,6-difluoro-phenyl]- methanesulfonamide | |
RU2792894C2 (en) | Method forasymmetrictransformation of substituted 2h-chromene-3-carboxy acids due to differential solubility | |
KR20060094974A (en) | New process for preparing an optically pure 2-morphinol derivative | |
Olbrycht et al. | Development of a Route to the Most Active Nafronyl Stereoisomer by Coupling Asymmetric Synthesis and Chiral Chromatography Separation |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
WWE | Wipo information: entry into national phase |
Ref document number: 2006755797 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2006260686 Country of ref document: AU |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2612763 Country of ref document: CA |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
WWW | Wipo information: withdrawn in national office |
Country of ref document: DE |
|
ENP | Entry into the national phase |
Ref document number: 2006260686 Country of ref document: AU Date of ref document: 20060621 Kind code of ref document: A |
|
WWP | Wipo information: published in national office |
Ref document number: 2006260686 Country of ref document: AU |
|
WWP | Wipo information: published in national office |
Ref document number: 2006755797 Country of ref document: EP |