CA2531165A1 - A method for the preparation of enantiomerically pure mirtazapine - Google Patents
A method for the preparation of enantiomerically pure mirtazapine Download PDFInfo
- Publication number
- CA2531165A1 CA2531165A1 CA002531165A CA2531165A CA2531165A1 CA 2531165 A1 CA2531165 A1 CA 2531165A1 CA 002531165 A CA002531165 A CA 002531165A CA 2531165 A CA2531165 A CA 2531165A CA 2531165 A1 CA2531165 A1 CA 2531165A1
- Authority
- CA
- Canada
- Prior art keywords
- acid
- combination
- solvent
- enantiomerically pure
- ring closure
- 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.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- A61P25/24—Antidepressants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/14—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a method for the preparation of enantiomerically pure mirtazapine, said method comprising a step of ring closure of a compound of formula (II) wherein X is a leaving group, said step comprising treatment with an acid, whereby mirlazapine with enantiomeric excess is formed by the ring closure of the compound of formula (II) with enantiomeric excess by treatment with a suitable acid in the absence of a solvent or a suitable combination of an acid and an organic solvent.
Claims (10)
1. A method for the preparation of enantiomerically pure mirtazapine, said method comprising a step of ring closure of a compound according to formula (II) wherein X is a leaving group, said step comprising treatment with an acid, characterised in that mirtazapine with enantiomeric excess is formed by the ring closure of the compound of formula (II) with enantiomeric excess by treatment with a suitable acid in the absence of a solvent or a suitable combination of an acid and an organic solvent.
2. The method of claim 1, characterised in that the ring closure occurs using a suitable acid in the absence of a solvent.
3. The method of claim 2, characterised in that the acid is a erotic acid or a protic acid derivative.
4. The method of claim 3, characterised in that the acid is polyphosphoric acid or phosphorus pentoxide in phosphoric acid.
5. The method according to claim 4, characterised in that the weight ratio between polyphosphoric acid and the compound according to formula II is less than 5 to 1.
6. The method of claim 1, characterised in that ring closure occurs using a suitable acid and organic solvent combination.
7. The method of claim 6, characterised in that the suitable acid and organic solvent combination is a erotic acid or erotic acid derivative in combination with a polar coordinating solvent.
8. The method of claim 6, characterised in that the suitable acid and organic solvent combination is a mineral acid in combination with a polar coordinating solvent.
9. The method of claim 7, characterised in that the suitable acid and organic solvent combination is polyphosphoric acid in combination with N-methylpyrrolidinone or DMF.
10. A method for the selection of an acid or an acid/solvent combination suitable for a stereospecific ring closure reaction of an enantiomerically pure compound according to the formula II and meaning of X of claim 1 leading to enantiomerically pure mirtazapine comprising testing the reaction by treatment of the enantiomerically pure compound with a candidate acid or a candidate acid/solvent combination and determining a loss of enantiomeric excess by the reaction and identifying an acid or an acid/solvent combination, as suitable if it results in the loss of less than 40%.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP03102095 | 2003-07-10 | ||
| EP03102095.1 | 2003-07-10 | ||
| PCT/EP2004/051357 WO2005005410A1 (en) | 2003-07-10 | 2004-07-05 | A method for the preparation of enantiomerically pure mirtazapine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2531165A1 true CA2531165A1 (en) | 2005-01-20 |
| CA2531165C CA2531165C (en) | 2011-08-30 |
Family
ID=34042934
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2531165A Expired - Fee Related CA2531165C (en) | 2003-07-10 | 2004-07-05 | A method for the preparation of enantiomerically pure mirtazapine |
Country Status (35)
| Country | Link |
|---|---|
| US (2) | US8058436B2 (en) |
| EP (1) | EP1656365B1 (en) |
| JP (1) | JP4668184B2 (en) |
| KR (1) | KR20060056315A (en) |
| CN (1) | CN100558722C (en) |
| AR (1) | AR046494A1 (en) |
| AT (1) | ATE433965T1 (en) |
| AU (1) | AU2004255874B2 (en) |
| BR (1) | BRPI0412447A (en) |
| CA (1) | CA2531165C (en) |
| CO (1) | CO5640123A2 (en) |
| CY (1) | CY1109327T1 (en) |
| DE (1) | DE602004021605D1 (en) |
| DK (1) | DK1656365T3 (en) |
| EC (1) | ECSP066271A (en) |
| ES (1) | ES2327123T3 (en) |
| HR (1) | HRP20051019A2 (en) |
| IL (1) | IL172549A0 (en) |
| IS (1) | IS2674B (en) |
| LT (1) | LT5382B (en) |
| LV (1) | LV13441B (en) |
| MX (1) | MXPA06000325A (en) |
| NO (1) | NO20056175L (en) |
| NZ (1) | NZ544360A (en) |
| PE (1) | PE20050323A1 (en) |
| PL (1) | PL1656365T3 (en) |
| PT (1) | PT1656365E (en) |
| RS (1) | RS20050972A (en) |
| RU (1) | RU2352566C2 (en) |
| SG (1) | SG144914A1 (en) |
| SI (1) | SI1656365T1 (en) |
| TW (1) | TWI335915B (en) |
| UA (1) | UA83666C2 (en) |
| WO (1) | WO2005005410A1 (en) |
| ZA (1) | ZA200600019B (en) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5080050B2 (en) * | 2005-09-26 | 2012-11-21 | 住友化学株式会社 | Method for producing optically active piperazine compound |
| CN102126982A (en) * | 2005-09-26 | 2011-07-20 | 住友化学株式会社 | Process for producing optically active piperazine compound |
| TW200808804A (en) * | 2006-05-22 | 2008-02-16 | Organon Nv | Mirtazapine for the treatment of neuropathic pain |
| TW200815370A (en) * | 2006-06-16 | 2008-04-01 | Organon Nv | Stereoselective synthesis of (S)-1-methyl-3-phenylpiperazine |
| WO2008099715A1 (en) * | 2007-02-09 | 2008-08-21 | Kaneka Corporation | Method for producing optically active 2-arylpiperazine derivative |
| JP5192707B2 (en) | 2007-03-22 | 2013-05-08 | 住友化学株式会社 | Manufacturing method of mirtazapine |
| WO2008125578A2 (en) | 2007-04-11 | 2008-10-23 | N.V. Organon | A method for the preparation of mirtazapine |
| US7994314B2 (en) | 2007-04-11 | 2011-08-09 | N.V. Organon | Method for the preparation of an enantiomerically pure benzazepine |
| KR101485418B1 (en) * | 2013-05-29 | 2015-01-26 | 주식회사 메디켐코리아 | A synthetic method of high purity mirtazapine |
| US10603272B2 (en) | 2015-02-27 | 2020-03-31 | Kindred Biosciences, Inc. | Stimulation of appetite and treatment of anorexia in dogs and cats |
| KR102540021B1 (en) * | 2020-12-02 | 2023-06-07 | (주)유케이케미팜 | Method for preparing mirtazapine suitable for mass production |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3959470A (en) * | 1972-11-28 | 1976-05-25 | Mikhail Davidovich Mashkovsky | Psychotropic medicinal preparation |
| NL189199C (en) * | 1975-04-05 | 1993-02-01 | Akzo Nv | PROCESS FOR THE PREPARATION OF PHARMACEUTICAL PREPARATIONS WITH ACTION ON THE CENTRAL NERVOUS SYSTEM BASED ON BENZ (ARYL) AZEPINE DERIVATIVES, THE PHARMACEUTICAL PREPARATIONS OBTAINED, AND METHOD FOR PREPARING THE PRODUCT TO BE USED. |
| IE903557A1 (en) * | 1989-10-05 | 1991-04-10 | Sankyo Co | Novel tetracyclic compounds having anti-allergic and¹anti-asthmatic activities, their preparation and use |
| DE69829202T2 (en) | 1997-11-14 | 2005-07-21 | Akzo Nobel N.V. | USE OF MIRTAZAPINE FOR THE MANUFACTURE OF A MEDICAMENT FOR THE TREATMENT OF SLEEP APNOES |
| JPH11222407A (en) * | 1997-11-14 | 1999-08-17 | Sankyo Co Ltd | New microbicidal |
| WO2000062782A1 (en) * | 1999-04-19 | 2000-10-26 | Teva Pharmaceutical Industries Ltd. | Novel synthesis and crystallization of piperazine ring-containing compounds |
| US20030069417A1 (en) * | 1999-04-19 | 2003-04-10 | Claude Singer | Novel synthesis and crystallization of piperazine ring-containing compounds |
| US6068695A (en) * | 1999-07-13 | 2000-05-30 | Bayer Corporation | Process for the continuous preparation of quinacridones |
| AU6476300A (en) | 1999-09-30 | 2001-05-10 | Sumika Fine Chemicals Co., Ltd. | Process for the preparation of a piperazine derivative |
| AU6474200A (en) * | 1999-12-13 | 2001-06-18 | Sumika Fine Chemicals Co., Ltd. | Process for the preparation of a pyridinemethanol compound |
| DK1257278T3 (en) | 2000-02-11 | 2006-06-12 | Akzo Nobel Nv | Use of mirtazapine for the treatment of sleep disorders |
| JP2001342188A (en) * | 2000-03-27 | 2001-12-11 | Takeda Chem Ind Ltd | Condensed pyrazole derivative, and its production method and use |
| TW200538100A (en) * | 2004-04-21 | 2005-12-01 | Akzo Nobel Nv | Mirtazapine salts |
-
2004
- 2004-05-07 UA UAA200600274A patent/UA83666C2/en unknown
- 2004-06-28 TW TW093118845A patent/TWI335915B/en not_active IP Right Cessation
- 2004-07-05 DE DE602004021605T patent/DE602004021605D1/en not_active Expired - Lifetime
- 2004-07-05 ES ES04741958T patent/ES2327123T3/en not_active Expired - Lifetime
- 2004-07-05 EP EP04741958A patent/EP1656365B1/en not_active Expired - Lifetime
- 2004-07-05 DK DK04741958T patent/DK1656365T3/en active
- 2004-07-05 US US10/564,193 patent/US8058436B2/en not_active Expired - Fee Related
- 2004-07-05 PL PL04741958T patent/PL1656365T3/en unknown
- 2004-07-05 KR KR1020067000511A patent/KR20060056315A/en not_active Abandoned
- 2004-07-05 RS YUP-2005/0972A patent/RS20050972A/en unknown
- 2004-07-05 CN CNB2004800194891A patent/CN100558722C/en not_active Expired - Lifetime
- 2004-07-05 SI SI200431183T patent/SI1656365T1/en unknown
- 2004-07-05 PT PT04741958T patent/PT1656365E/en unknown
- 2004-07-05 MX MXPA06000325A patent/MXPA06000325A/en active IP Right Grant
- 2004-07-05 SG SG200805127-8A patent/SG144914A1/en unknown
- 2004-07-05 RU RU2006103992/04A patent/RU2352566C2/en not_active IP Right Cessation
- 2004-07-05 NZ NZ544360A patent/NZ544360A/en not_active IP Right Cessation
- 2004-07-05 JP JP2006518216A patent/JP4668184B2/en not_active Expired - Lifetime
- 2004-07-05 WO PCT/EP2004/051357 patent/WO2005005410A1/en active IP Right Grant
- 2004-07-05 BR BRPI0412447-2A patent/BRPI0412447A/en not_active IP Right Cessation
- 2004-07-05 CA CA2531165A patent/CA2531165C/en not_active Expired - Fee Related
- 2004-07-05 AU AU2004255874A patent/AU2004255874B2/en not_active Expired
- 2004-07-05 AT AT04741958T patent/ATE433965T1/en active
- 2004-07-05 HR HR20051019A patent/HRP20051019A2/en not_active Application Discontinuation
- 2004-07-07 PE PE2004000653A patent/PE20050323A1/en not_active Application Discontinuation
- 2004-07-08 AR ARP040102412A patent/AR046494A1/en not_active Application Discontinuation
-
2005
- 2005-12-12 LT LT2005107A patent/LT5382B/en not_active IP Right Cessation
- 2005-12-13 IL IL172549A patent/IL172549A0/en not_active IP Right Cessation
- 2005-12-15 IS IS8184A patent/IS2674B/en unknown
- 2005-12-23 NO NO20056175A patent/NO20056175L/en not_active Application Discontinuation
-
2006
- 2006-01-03 ZA ZA200600019A patent/ZA200600019B/en unknown
- 2006-01-09 EC EC2006006271A patent/ECSP066271A/en unknown
- 2006-01-10 CO CO06001617A patent/CO5640123A2/en not_active Application Discontinuation
- 2006-02-10 LV LVP-06-21A patent/LV13441B/en unknown
-
2008
- 2008-07-02 US US12/667,969 patent/US20100179319A1/en not_active Abandoned
-
2009
- 2009-08-25 CY CY20091100894T patent/CY1109327T1/en unknown
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20150706 |