RU2012118499A - Способ получения пиразинонового ингибитора тромбина и промежуточных соединений для его получения - Google Patents
Способ получения пиразинонового ингибитора тромбина и промежуточных соединений для его получения Download PDFInfo
- Publication number
- RU2012118499A RU2012118499A RU2012118499/04A RU2012118499A RU2012118499A RU 2012118499 A RU2012118499 A RU 2012118499A RU 2012118499/04 A RU2012118499/04 A RU 2012118499/04A RU 2012118499 A RU2012118499 A RU 2012118499A RU 2012118499 A RU2012118499 A RU 2012118499A
- Authority
- RU
- Russia
- Prior art keywords
- difluoro
- formula
- fluoropyridine
- compound
- salt
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract 15
- 238000004519 manufacturing process Methods 0.000 title claims 3
- 108090000190 Thrombin Proteins 0.000 title 1
- 239000003112 inhibitor Substances 0.000 title 1
- 229960004072 thrombin Drugs 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract 21
- 150000003839 salts Chemical class 0.000 claims abstract 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract 10
- -1 2,2-difluoro-2- (2-pyridyl) ethylamino Chemical group 0.000 claims abstract 6
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 claims abstract 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims abstract 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims abstract 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract 6
- QLRSPKRGYAGOEC-UHFFFAOYSA-N (3-fluoropyridin-2-yl)methanamine Chemical compound NCC1=NC=CC=C1F QLRSPKRGYAGOEC-UHFFFAOYSA-N 0.000 claims abstract 5
- VZFPSCNTFBJZHB-UHFFFAOYSA-N 3-fluoropyridine-2-carbonitrile Chemical compound FC1=CC=CN=C1C#N VZFPSCNTFBJZHB-UHFFFAOYSA-N 0.000 claims abstract 5
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims abstract 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims abstract 4
- 239000002253 acid Substances 0.000 claims abstract 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims abstract 4
- RTZZBUQTHNQTSR-UHFFFAOYSA-N 2,2-difluoro-2-pyridin-2-ylethanol Chemical compound OCC(F)(F)C1=CC=CC=N1 RTZZBUQTHNQTSR-UHFFFAOYSA-N 0.000 claims abstract 3
- 239000004215 Carbon black (E152) Substances 0.000 claims abstract 3
- 150000002148 esters Chemical class 0.000 claims abstract 3
- 229930195733 hydrocarbon Natural products 0.000 claims abstract 3
- 150000002430 hydrocarbons Chemical class 0.000 claims abstract 3
- 239000000203 mixture Substances 0.000 claims abstract 3
- 239000003960 organic solvent Substances 0.000 claims abstract 3
- 239000002904 solvent Substances 0.000 claims abstract 3
- TYKNQWWXUIYRSZ-UHFFFAOYSA-N 2,2-difluoro-2-pyridin-2-ylethanamine Chemical compound NCC(F)(F)C1=CC=CC=N1 TYKNQWWXUIYRSZ-UHFFFAOYSA-N 0.000 claims abstract 2
- JDBIYZFYKSYXPK-UHFFFAOYSA-N 2-chloro-3-ethylpyrazine Chemical compound CCC1=NC=CN=C1Cl JDBIYZFYKSYXPK-UHFFFAOYSA-N 0.000 claims abstract 2
- NVFNJYKITCYHPS-UHFFFAOYSA-N C(C)C1=NC=CN=C1NCC(C1=NC=CC=C1)(F)F Chemical compound C(C)C1=NC=CN=C1NCC(C1=NC=CC=C1)(F)F NVFNJYKITCYHPS-UHFFFAOYSA-N 0.000 claims abstract 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims abstract 2
- 229940077388 benzenesulfonate Drugs 0.000 claims abstract 2
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 claims abstract 2
- 150000002576 ketones Chemical class 0.000 claims abstract 2
- 238000000746 purification Methods 0.000 claims abstract 2
- 239000012453 solvate Substances 0.000 claims abstract 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims 6
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 claims 2
- 239000007868 Raney catalyst Substances 0.000 claims 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 claims 2
- 229910000564 Raney nickel Inorganic materials 0.000 claims 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims 2
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 claims 2
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 claims 2
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 claims 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims 1
- UUUYCUQKIMUADO-UHFFFAOYSA-N 2,2-difluoro-2-pyridin-2-ylethanesulfonic acid Chemical compound OS(=O)(=O)CC(F)(F)C1=CC=CC=N1 UUUYCUQKIMUADO-UHFFFAOYSA-N 0.000 claims 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical group CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 claims 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims 1
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 claims 1
- 229940011051 isopropyl acetate Drugs 0.000 claims 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 claims 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 claims 1
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 claims 1
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
- C07D401/14—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 three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B61/00—Other general methods
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Catalysts (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN2663/CHE/2009 | 2009-11-03 | ||
| IN2663CH2009 | 2009-11-03 | ||
| PCT/US2010/055176 WO2011056806A1 (en) | 2009-11-03 | 2010-11-02 | Process for the preparation of pyrazinone thrombin inhibitor and its intermediates |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| RU2012118499A true RU2012118499A (ru) | 2013-12-10 |
Family
ID=43926105
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2012118499/04A RU2012118499A (ru) | 2009-11-03 | 2010-11-02 | Способ получения пиразинонового ингибитора тромбина и промежуточных соединений для его получения |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US8541580B2 (enExample) |
| EP (1) | EP2496087A4 (enExample) |
| JP (1) | JP2013510159A (enExample) |
| KR (1) | KR20120106727A (enExample) |
| CN (1) | CN102711481A (enExample) |
| AU (1) | AU2010315338A1 (enExample) |
| CA (1) | CA2778922A1 (enExample) |
| MX (1) | MX2012005165A (enExample) |
| RU (1) | RU2012118499A (enExample) |
| WO (1) | WO2011056806A1 (enExample) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10016417B2 (en) | 2011-11-07 | 2018-07-10 | Diakron Pharmaceuticals, Inc. | Extended release formulation of a direct thrombin inhibitor |
| CN108430986B (zh) | 2015-10-26 | 2021-08-31 | 拜耳作物科学股份公司 | 作为有害生物控制剂的稠合双环杂环衍生物 |
| PH12021552065A1 (en) | 2019-02-26 | 2022-05-23 | Bayer Ag | Condensed bicyclic heterocyclic derivatives as pest control agents |
| CN113710669A (zh) | 2019-02-26 | 2021-11-26 | 拜耳公司 | 作为农药的稠合双环杂环衍生物 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6147078A (en) * | 1998-05-19 | 2000-11-14 | Merck & Co., Inc. | Pyrazinone thrombin inhibitors |
| UA58636C2 (uk) * | 1999-06-04 | 2003-08-15 | Мерк Енд Ко., Інк. | Піразинонові інгібітори тромбіну, фармацевтична композиція, спосіб інгібування утворення тромбів у крові, спосіб лікування станів, пов'язаних із тромбоутворенням |
| AU2002232533A1 (en) * | 2000-12-06 | 2002-06-18 | Merck & Co., Inc. | Process for making a thrombin inhibitor |
| EP1422221A1 (en) | 2002-11-20 | 2004-05-26 | Bayer CropScience SA | Novel process for the preparation of 2-aminomethylpyridine derivative |
-
2010
- 2010-11-02 MX MX2012005165A patent/MX2012005165A/es active IP Right Grant
- 2010-11-02 EP EP10828989.3A patent/EP2496087A4/en not_active Withdrawn
- 2010-11-02 KR KR1020127010789A patent/KR20120106727A/ko not_active Ceased
- 2010-11-02 US US12/938,297 patent/US8541580B2/en not_active Expired - Fee Related
- 2010-11-02 CN CN2010800499062A patent/CN102711481A/zh active Pending
- 2010-11-02 AU AU2010315338A patent/AU2010315338A1/en not_active Abandoned
- 2010-11-02 RU RU2012118499/04A patent/RU2012118499A/ru not_active Application Discontinuation
- 2010-11-02 WO PCT/US2010/055176 patent/WO2011056806A1/en not_active Ceased
- 2010-11-02 CA CA2778922A patent/CA2778922A1/en not_active Abandoned
- 2010-11-02 JP JP2012537955A patent/JP2013510159A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| KR20120106727A (ko) | 2012-09-26 |
| US8541580B2 (en) | 2013-09-24 |
| EP2496087A1 (en) | 2012-09-12 |
| US20110105753A1 (en) | 2011-05-05 |
| AU2010315338A1 (en) | 2012-05-24 |
| CA2778922A1 (en) | 2011-05-12 |
| WO2011056806A1 (en) | 2011-05-12 |
| CN102711481A (zh) | 2012-10-03 |
| MX2012005165A (es) | 2012-08-08 |
| EP2496087A4 (en) | 2013-06-19 |
| JP2013510159A (ja) | 2013-03-21 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FA92 | Acknowledgement of application withdrawn (lack of supplementary materials submitted) |
Effective date: 20150122 |