CA2520893C - Process for the preparation of 1-n-(phenyl)-2-n-(phenyl)pyrrolidine-1,2-dicarboxamide derivatives and 1-(phenylcarbamoyl)pyrrolidine-2-carboxylic acid derivatives as intermediates - Google Patents
Process for the preparation of 1-n-(phenyl)-2-n-(phenyl)pyrrolidine-1,2-dicarboxamide derivatives and 1-(phenylcarbamoyl)pyrrolidine-2-carboxylic acid derivatives as intermediates Download PDFInfo
- Publication number
- CA2520893C CA2520893C CA2520893A CA2520893A CA2520893C CA 2520893 C CA2520893 C CA 2520893C CA 2520893 A CA2520893 A CA 2520893A CA 2520893 A CA2520893 A CA 2520893A CA 2520893 C CA2520893 C CA 2520893C
- Authority
- CA
- Canada
- Prior art keywords
- oxomorpholin
- formula
- phenyl
- dicarboxamide
- oxo
- 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.)
- Expired - Fee Related
Links
- 238000000034 method Methods 0.000 title claims abstract description 43
- 230000008569 process Effects 0.000 title claims abstract description 34
- 238000002360 preparation method Methods 0.000 title claims abstract description 27
- RVEDFFORAVMBLV-UHFFFAOYSA-N pyrrolidine-1,2-dicarboxamide Chemical class NC(=O)C1CCCN1C(N)=O RVEDFFORAVMBLV-UHFFFAOYSA-N 0.000 title claims description 3
- 239000000543 intermediate Substances 0.000 title abstract description 6
- ZEEAHHXBZHTCOI-UHFFFAOYSA-N 1-(phenylcarbamoyl)pyrrolidine-2-carboxylic acid Chemical class OC(=O)C1CCCN1C(=O)NC1=CC=CC=C1 ZEEAHHXBZHTCOI-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 77
- -1 COOA Chemical group 0.000 claims description 126
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 40
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
- 239000000203 mixture Substances 0.000 claims description 26
- 239000012453 solvate Substances 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 23
- 125000004432 carbon atom Chemical group C* 0.000 claims description 21
- 238000006243 chemical reaction Methods 0.000 claims description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 16
- 239000002253 acid Substances 0.000 claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 15
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- 230000015572 biosynthetic process Effects 0.000 claims description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 8
- 239000002585 base Substances 0.000 claims description 7
- 239000012442 inert solvent Substances 0.000 claims description 7
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
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- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 5
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims description 4
- 150000001340 alkali metals Chemical class 0.000 claims description 4
- 150000008064 anhydrides Chemical class 0.000 claims description 4
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 4
- 239000003153 chemical reaction reagent Substances 0.000 claims description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 4
- 229910052783 alkali metal Inorganic materials 0.000 claims description 3
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims description 2
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 claims description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
- 239000011877 solvent mixture Substances 0.000 claims description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims 2
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- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 1
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- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
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- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
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- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical class OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
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- WTVXIBRMWGUIMI-UHFFFAOYSA-N trifluoro($l^{1}-oxidanylsulfonyl)methane Chemical group [O]S(=O)(=O)C(F)(F)F WTVXIBRMWGUIMI-UHFFFAOYSA-N 0.000 description 1
- 125000005500 uronium group Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or 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 to ring carbon atoms
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (11)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10315377.2 | 2003-04-03 | ||
| DE10315377A DE10315377A1 (de) | 2003-04-03 | 2003-04-03 | Carbonylverbindungen |
| DE10327428.6 | 2003-06-18 | ||
| DE10327428A DE10327428A1 (de) | 2003-06-18 | 2003-06-18 | Ethinylprolinderivate |
| DE2003129295 DE10329295A1 (de) | 2003-06-30 | 2003-06-30 | Carbonylverbindungen |
| DE10329295.0 | 2003-06-30 | ||
| DE10329457.0 | 2003-07-01 | ||
| DE10329457A DE10329457A1 (de) | 2003-04-03 | 2003-07-01 | Ethinylprolinderivate |
| DE10334174.9 | 2003-07-26 | ||
| DE2003134174 DE10334174A1 (de) | 2003-07-26 | 2003-07-26 | Pyrrolidinderivate und Verfahren zur Herstellung |
| PCT/EP2004/002405 WO2004087695A1 (de) | 2003-04-03 | 2004-03-09 | Verfahren zur herstellung von pyrrolidin-1,2-dicarbonsäure-1-(phenyl(-amid))-2-(phenyl(-amid)) derivaten und 1-(phenylcarbamoyl)-pyrrolidin-2-carbonsäure derivate als zwischenprodukte |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2520893A1 CA2520893A1 (en) | 2004-10-14 |
| CA2520893C true CA2520893C (en) | 2012-07-10 |
Family
ID=33136213
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2520893A Expired - Fee Related CA2520893C (en) | 2003-04-03 | 2004-03-09 | Process for the preparation of 1-n-(phenyl)-2-n-(phenyl)pyrrolidine-1,2-dicarboxamide derivatives and 1-(phenylcarbamoyl)pyrrolidine-2-carboxylic acid derivatives as intermediates |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US7504500B2 (enExample) |
| EP (1) | EP1608646B1 (enExample) |
| JP (1) | JP4634369B2 (enExample) |
| KR (1) | KR20050118709A (enExample) |
| AR (1) | AR043831A1 (enExample) |
| AT (1) | ATE366732T1 (enExample) |
| AU (1) | AU2004226280B2 (enExample) |
| BR (1) | BRPI0408888A (enExample) |
| CA (1) | CA2520893C (enExample) |
| DE (2) | DE10329457A1 (enExample) |
| ES (1) | ES2287708T3 (enExample) |
| MX (1) | MXPA05010433A (enExample) |
| PE (1) | PE20050395A1 (enExample) |
| PL (1) | PL377138A1 (enExample) |
| TW (1) | TW200500339A (enExample) |
| WO (1) | WO2004087695A1 (enExample) |
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050119266A1 (en) * | 2003-10-01 | 2005-06-02 | Yan Shi | Pyrrolidine and piperidine derivatives as factor Xa inhibitors |
| DE102004004731A1 (de) * | 2004-01-30 | 2005-08-18 | Merck Patent Gmbh | Harnstoffderivate |
| DE102004045796A1 (de) * | 2004-09-22 | 2006-03-23 | Merck Patent Gmbh | Arzneimittel enthaltend Carbonylverbindungen sowie deren Verwendung |
| DE102004047254A1 (de) * | 2004-09-29 | 2006-04-13 | Merck Patent Gmbh | Carbonylverbindungen |
| DE102004050283A1 (de) * | 2004-10-15 | 2006-04-27 | Lanxess Deutschland Gmbh | 4-Aminophenyl-morpholinon-Derivate und deren Herstellung |
| US7301817B2 (en) | 2005-10-27 | 2007-11-27 | Sandisk Corporation | Method for programming of multi-state non-volatile memory using smart verify |
| KR101020440B1 (ko) * | 2005-11-16 | 2011-03-08 | 에프. 호프만-라 로슈 아게 | 응고 인자 Ｘａ의 억제제로서의 피롤리딘 유도체 |
| EP1818330A1 (de) * | 2006-02-14 | 2007-08-15 | Boehringer Ingelheim Pharma GmbH & Co.KG | Substituierte Prolinamide, deren Herstellung und deren Verwendung als Arzneimittel |
| JP5263686B2 (ja) | 2006-05-16 | 2013-08-14 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 置換プロリンアミド、その製造及び薬物としての使用 |
| US8673920B2 (en) | 2009-05-06 | 2014-03-18 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
| EP2632465B1 (en) | 2010-10-27 | 2015-12-30 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
| WO2012058134A1 (en) | 2010-10-29 | 2012-05-03 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
| CA2844310A1 (en) | 2011-08-19 | 2013-02-28 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
| TW201317213A (zh) | 2011-09-16 | 2013-05-01 | Merck Sharp & Dohme | 腎外髓質鉀通道抑制劑 |
| EP2771005B1 (en) | 2011-10-25 | 2016-05-18 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
| WO2013062900A1 (en) | 2011-10-25 | 2013-05-02 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
| EP2773351B1 (en) | 2011-10-31 | 2017-08-23 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
| US9108947B2 (en) | 2011-10-31 | 2015-08-18 | Merck Sharp & Dohme Corp. | Inhibitors of the Renal Outer Medullary Potassium channel |
| US9139585B2 (en) | 2011-10-31 | 2015-09-22 | Merck Sharp & Dohme Corp. | Inhibitors of the Renal Outer Medullary Potassium channel |
| WO2013090271A1 (en) | 2011-12-16 | 2013-06-20 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
| AR092031A1 (es) | 2012-07-26 | 2015-03-18 | Merck Sharp & Dohme | Inhibidores del canal de potasio medular externo renal |
| WO2014085210A1 (en) | 2012-11-29 | 2014-06-05 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
| WO2014099633A2 (en) | 2012-12-19 | 2014-06-26 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
| EP2956142B1 (en) | 2013-02-18 | 2017-09-20 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
| EP2968288B1 (en) | 2013-03-15 | 2018-07-04 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
| WO2015017305A1 (en) | 2013-07-31 | 2015-02-05 | Merck Sharp & Dohme Corp | Inhibitors of the renal outer medullary potassium channel |
| WO2015065866A1 (en) | 2013-10-31 | 2015-05-07 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5822111B2 (ja) | 1977-10-29 | 1983-05-06 | 協和醗酵工業株式会社 | 柑橘類果実の改質剤 |
| JPS63232846A (ja) | 1987-03-20 | 1988-09-28 | Haruo Ogura | 新規な固定相担体 |
| WO1998022432A1 (en) * | 1996-11-18 | 1998-05-28 | Yamanouchi Pharmaceutical Co., Ltd. | Novel acylamino-substituted acylanilide derivatives or pharmaceutical composition comprising the same |
| US7030141B2 (en) * | 2001-11-29 | 2006-04-18 | Christopher Franklin Bigge | Inhibitors of factor Xa and other serine proteases involved in the coagulation cascade |
-
2003
- 2003-07-01 DE DE10329457A patent/DE10329457A1/de not_active Withdrawn
-
2004
- 2004-03-09 EP EP04718646A patent/EP1608646B1/de not_active Expired - Lifetime
- 2004-03-09 DE DE502004004294T patent/DE502004004294D1/de not_active Expired - Lifetime
- 2004-03-09 CA CA2520893A patent/CA2520893C/en not_active Expired - Fee Related
- 2004-03-09 AU AU2004226280A patent/AU2004226280B2/en not_active Ceased
- 2004-03-09 JP JP2006504602A patent/JP4634369B2/ja not_active Expired - Fee Related
- 2004-03-09 AT AT04718646T patent/ATE366732T1/de not_active IP Right Cessation
- 2004-03-09 PL PL377138A patent/PL377138A1/pl unknown
- 2004-03-09 ES ES04718646T patent/ES2287708T3/es not_active Expired - Lifetime
- 2004-03-09 MX MXPA05010433A patent/MXPA05010433A/es not_active Application Discontinuation
- 2004-03-09 BR BRPI0408888-3A patent/BRPI0408888A/pt not_active Application Discontinuation
- 2004-03-09 US US10/551,670 patent/US7504500B2/en not_active Expired - Fee Related
- 2004-03-09 WO PCT/EP2004/002405 patent/WO2004087695A1/de not_active Ceased
- 2004-03-09 KR KR1020057018640A patent/KR20050118709A/ko not_active Withdrawn
- 2004-03-31 TW TW093108904A patent/TW200500339A/zh unknown
- 2004-04-02 PE PE2004000349A patent/PE20050395A1/es not_active Application Discontinuation
- 2004-04-02 AR ARP040101113A patent/AR043831A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AU2004226280A1 (en) | 2004-10-14 |
| PE20050395A1 (es) | 2005-06-04 |
| US20060211692A1 (en) | 2006-09-21 |
| KR20050118709A (ko) | 2005-12-19 |
| EP1608646A1 (de) | 2005-12-28 |
| PL377138A1 (pl) | 2006-01-23 |
| AU2004226280B2 (en) | 2010-06-17 |
| TW200500339A (en) | 2005-01-01 |
| ATE366732T1 (de) | 2007-08-15 |
| AR043831A1 (es) | 2005-08-17 |
| MXPA05010433A (es) | 2005-11-04 |
| ES2287708T3 (es) | 2007-12-16 |
| JP4634369B2 (ja) | 2011-02-16 |
| BRPI0408888A (pt) | 2006-04-11 |
| DE10329457A1 (de) | 2005-01-20 |
| JP2006522037A (ja) | 2006-09-28 |
| WO2004087695A1 (de) | 2004-10-14 |
| CA2520893A1 (en) | 2004-10-14 |
| US7504500B2 (en) | 2009-03-17 |
| EP1608646B1 (de) | 2007-07-11 |
| DE502004004294D1 (de) | 2007-08-23 |
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