CA2640081A1 - Production de cabergoline et nouvelle forme polymorphique de ce compose - Google Patents
Production de cabergoline et nouvelle forme polymorphique de ce compose Download PDFInfo
- Publication number
- CA2640081A1 CA2640081A1 CA002640081A CA2640081A CA2640081A1 CA 2640081 A1 CA2640081 A1 CA 2640081A1 CA 002640081 A CA002640081 A CA 002640081A CA 2640081 A CA2640081 A CA 2640081A CA 2640081 A1 CA2640081 A1 CA 2640081A1
- Authority
- CA
- Canada
- Prior art keywords
- cabergoline
- tame
- solvent
- methyl ether
- solution
- 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.)
- Abandoned
Links
- KORNTPPJEAJQIU-KJXAQDMKSA-N Cabaser Chemical compound C1=CC([C@H]2C[C@H](CN(CC=C)[C@@H]2C2)C(=O)N(CCCN(C)C)C(=O)NCC)=C3C2=CNC3=C1 KORNTPPJEAJQIU-KJXAQDMKSA-N 0.000 title claims abstract description 116
- 229960004596 cabergoline Drugs 0.000 title claims abstract description 83
- 238000004519 manufacturing process Methods 0.000 title description 4
- HVZJRWJGKQPSFL-UHFFFAOYSA-N tert-Amyl methyl ether Chemical compound CCC(C)(C)OC HVZJRWJGKQPSFL-UHFFFAOYSA-N 0.000 claims abstract description 52
- 238000000034 method Methods 0.000 claims abstract description 43
- 239000002904 solvent Substances 0.000 claims description 31
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims description 30
- 239000000243 solution Substances 0.000 claims description 29
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- 239000012453 solvate Substances 0.000 claims description 12
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 claims description 8
- 238000002441 X-ray diffraction Methods 0.000 claims description 8
- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 claims description 6
- AUHZEENZYGFFBQ-UHFFFAOYSA-N 1,3,5-trimethylbenzene Chemical compound CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 claims description 6
- 239000000725 suspension Substances 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 5
- 238000006243 chemical reaction Methods 0.000 claims description 4
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 4
- QUGUFLJIAFISSW-UHFFFAOYSA-N 1,4-difluorobenzene Chemical compound FC1=CC=C(F)C=C1 QUGUFLJIAFISSW-UHFFFAOYSA-N 0.000 claims description 3
- RJCGZNCCVKIBHO-UHFFFAOYSA-N 1-chloro-4-fluorobenzene Chemical compound FC1=CC=C(Cl)C=C1 RJCGZNCCVKIBHO-UHFFFAOYSA-N 0.000 claims description 3
- WRWPPGUCZBJXKX-UHFFFAOYSA-N 1-fluoro-4-methylbenzene Chemical compound CC1=CC=C(F)C=C1 WRWPPGUCZBJXKX-UHFFFAOYSA-N 0.000 claims description 3
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims description 2
- 239000011261 inert gas Substances 0.000 claims description 2
- 239000008096 xylene Substances 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims 1
- 238000010626 work up procedure Methods 0.000 claims 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- 239000000047 product Substances 0.000 description 11
- 239000007787 solid Substances 0.000 description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 238000000113 differential scanning calorimetry Methods 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 239000012429 reaction media Substances 0.000 description 4
- 238000004482 13C cross polarization magic angle spinning Methods 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 238000004817 gas chromatography Methods 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 238000010348 incorporation Methods 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- AWFDCTXCTHGORH-HGHGUNKESA-N 6-[4-[(6ar,9r,10ar)-5-bromo-7-methyl-6,6a,8,9,10,10a-hexahydro-4h-indolo[4,3-fg]quinoline-9-carbonyl]piperazin-1-yl]-1-methylpyridin-2-one Chemical class O=C([C@H]1CN([C@H]2[C@@H](C=3C=CC=C4NC(Br)=C(C=34)C2)C1)C)N(CC1)CCN1C1=CC=CC(=O)N1C AWFDCTXCTHGORH-HGHGUNKESA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- PVEOYINWKBTPIZ-UHFFFAOYSA-N but-3-enoic acid Chemical compound OC(=O)CC=C PVEOYINWKBTPIZ-UHFFFAOYSA-N 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 238000003921 particle size analysis Methods 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 238000000638 solvent extraction Methods 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- -1 COOH ' Chemical compound 0.000 description 1
- 229910016523 CuKa Inorganic materials 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- 208000027771 Obstructive airways disease Diseases 0.000 description 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
- 102000003946 Prolactin Human genes 0.000 description 1
- 108010057464 Prolactin Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical class O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 239000003570 air Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000004410 intraocular pressure Effects 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 239000011236 particulate material Substances 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 229940097325 prolactin Drugs 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D457/00—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid
- C07D457/04—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 8
- C07D457/06—Lysergic acid amides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Ophthalmology & Optometry (AREA)
- Pulmonology (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0602557.1A GB0602557D0 (en) | 2006-02-08 | 2006-02-08 | Production of cabergoline and novel polymorphic form thereof |
| GB0602557.1 | 2006-02-08 | ||
| PCT/GB2007/000397 WO2007091039A2 (fr) | 2006-02-08 | 2007-02-06 | Production de cabergoline et nouvelle forme polymorphique de ce composé |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2640081A1 true CA2640081A1 (fr) | 2007-08-16 |
Family
ID=36119736
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002640081A Abandoned CA2640081A1 (fr) | 2006-02-08 | 2007-02-06 | Production de cabergoline et nouvelle forme polymorphique de ce compose |
Country Status (9)
| Country | Link |
|---|---|
| EP (1) | EP2007761A2 (fr) |
| JP (1) | JP2009526030A (fr) |
| CN (1) | CN101384589A (fr) |
| AU (1) | AU2007213571A1 (fr) |
| BR (1) | BRPI0707161A2 (fr) |
| CA (1) | CA2640081A1 (fr) |
| GB (1) | GB0602557D0 (fr) |
| IL (1) | IL192870A0 (fr) |
| WO (1) | WO2007091039A2 (fr) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1620101A4 (fr) | 2003-05-08 | 2008-07-09 | Ivax Pharmaceuticals Sro | Polymorphes de la cabergoline |
| US7939665B2 (en) * | 2007-05-04 | 2011-05-10 | Apotex Pharmachem Inc. | Efficient process for the preparation of cabergoline and its intermediates |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4526892A (en) * | 1981-03-03 | 1985-07-02 | Farmitalia Carlo Erba, S.P.A. | Dimethylaminoalkyl-3-(ergoline-8'βcarbonyl)-ureas |
| CA2412861A1 (fr) * | 2001-04-16 | 2002-10-31 | Finetech Laboratories Ltd. | Procede et intermediaires de production de cabergoline et de composes associes |
| IL155545A (en) * | 2003-04-21 | 2009-12-24 | Finetech Pharmaceutical Ltd | Solvate form of cabergoline |
| EP1620101A4 (fr) * | 2003-05-08 | 2008-07-09 | Ivax Pharmaceuticals Sro | Polymorphes de la cabergoline |
-
2006
- 2006-02-08 GB GBGB0602557.1A patent/GB0602557D0/en not_active Ceased
-
2007
- 2007-02-06 CN CNA2007800047542A patent/CN101384589A/zh active Pending
- 2007-02-06 BR BRPI0707161-2A patent/BRPI0707161A2/pt not_active IP Right Cessation
- 2007-02-06 AU AU2007213571A patent/AU2007213571A1/en not_active Abandoned
- 2007-02-06 WO PCT/GB2007/000397 patent/WO2007091039A2/fr active Application Filing
- 2007-02-06 CA CA002640081A patent/CA2640081A1/fr not_active Abandoned
- 2007-02-06 EP EP07705129A patent/EP2007761A2/fr not_active Withdrawn
- 2007-02-06 JP JP2008553820A patent/JP2009526030A/ja active Pending
-
2008
- 2008-07-17 IL IL192870A patent/IL192870A0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AU2007213571A1 (en) | 2007-08-16 |
| WO2007091039A3 (fr) | 2007-10-18 |
| IL192870A0 (en) | 2009-02-11 |
| EP2007761A2 (fr) | 2008-12-31 |
| BRPI0707161A2 (pt) | 2011-04-26 |
| GB0602557D0 (en) | 2006-03-22 |
| WO2007091039A8 (fr) | 2008-11-13 |
| CN101384589A (zh) | 2009-03-11 |
| JP2009526030A (ja) | 2009-07-16 |
| WO2007091039A2 (fr) | 2007-08-16 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |