MD4392B1 - Procedeu de sinteză a (2E)-3-(3,4-dimetoxifenil)prop-2-ennitrilului şi aplicarea acestuia în sinteza ivabradinei şi a sărurilor sale de adiţie cu un acid acceptabil farmaceutic - Google Patents
Procedeu de sinteză a (2E)-3-(3,4-dimetoxifenil)prop-2-ennitrilului şi aplicarea acestuia în sinteza ivabradinei şi a sărurilor sale de adiţie cu un acid acceptabil farmaceutic Download PDFInfo
- Publication number
- MD4392B1 MD4392B1 MDA20130082A MD20130082A MD4392B1 MD 4392 B1 MD4392 B1 MD 4392B1 MD A20130082 A MDA20130082 A MD A20130082A MD 20130082 A MD20130082 A MD 20130082A MD 4392 B1 MD4392 B1 MD 4392B1
- Authority
- MD
- Moldova
- Prior art keywords
- synthesis
- enenitrile
- ivabradine
- dimethoxyphenyl
- prop
- Prior art date
Links
- 230000015572 biosynthetic process Effects 0.000 title abstract 4
- 238000000034 method Methods 0.000 title abstract 4
- 238000003786 synthesis reaction Methods 0.000 title abstract 4
- WGPTVEZJYRFEGT-ONEGZZNKSA-N (e)-3-(3,4-dimethoxyphenyl)prop-2-enenitrile Chemical compound COC1=CC=C(\C=C\C#N)C=C1OC WGPTVEZJYRFEGT-ONEGZZNKSA-N 0.000 title abstract 2
- ACRHBAYQBXXRTO-OAQYLSRUSA-N ivabradine Chemical compound C1CC2=CC(OC)=C(OC)C=C2CC(=O)N1CCCN(C)C[C@H]1CC2=C1C=C(OC)C(OC)=C2 ACRHBAYQBXXRTO-OAQYLSRUSA-N 0.000 title abstract 2
- 229960003825 ivabradine Drugs 0.000 title abstract 2
- 150000003839 salts Chemical class 0.000 title abstract 2
- 239000002253 acid Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 abstract 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 abstract 2
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 abstract 1
- 239000003054 catalyst Substances 0.000 abstract 1
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 238000005859 coupling reaction Methods 0.000 abstract 1
- 150000004677 hydrates Chemical class 0.000 abstract 1
- 239000003446 ligand Substances 0.000 abstract 1
- 239000003960 organic solvent Substances 0.000 abstract 1
- 229910052763 palladium Inorganic materials 0.000 abstract 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/32—Separation; Purification; Stabilisation; Use of additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
- B01J23/38—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals
- B01J23/40—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals of the platinum group metals
- B01J23/44—Palladium
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
- C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
- C07C255/34—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring with cyano groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by unsaturated carbon chains
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/16—Benzazepines; Hydrogenated benzazepines
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Heart & Thoracic Surgery (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Materials Engineering (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Saccharide Compounds (AREA)
- Catalysts (AREA)
Abstract
Invenţia se referă la un procedeu de sinteză a (2E)-3-(3,4-dimetoxifenil)prop-2-ennitrilului cu formula (I):care constă în aceea că compusul cu formula (IX):este supus unei reacţii de cuplare cu acrilonitril în prezenţa unui catalizator de paladiu, unui ligand, unei baze şi a unui agent de transfer al fazei într-un solvent organic pentru a obţine compusul cu formula (I).Invenţia se referă, de asemenea, la un procedeu de sinteză a ivabradinei, a sărurilor sale acceptabile farmaceutic şi hidraţilor acestora, cu utilizarea compusului cu formula (I). Procedeul menţionat asigură un procent înalt al randamentului produsului finit.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR1260576A FR2997696B1 (fr) | 2012-11-08 | 2012-11-08 | Nouveau procede de synthese du (2e)-3-(3,4-dimethoxyphenyl)prop-2-enenitrile, et application a la synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| MD20130082A2 MD20130082A2 (ro) | 2014-05-31 |
| MD4392B1 true MD4392B1 (ro) | 2016-01-31 |
| MD4392C1 MD4392C1 (ro) | 2016-08-31 |
Family
ID=47598957
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MDA20130082A MD4392C1 (ro) | 2012-11-08 | 2013-10-30 | Procedeu de sinteză a (2E)-3-(3,4-dimetoxifenil)prop-2-ennitrilului şi aplicarea acestuia în sinteza ivabradinei şi a sărurilor sale de adiţie cu un acid acceptabil farmaceutic |
Country Status (35)
| Country | Link |
|---|---|
| US (1) | US8779122B2 (ro) |
| EP (1) | EP2730562B1 (ro) |
| JP (2) | JP6058519B2 (ro) |
| KR (1) | KR20140059731A (ro) |
| CN (1) | CN103804225B (ro) |
| AR (1) | AR093373A1 (ro) |
| AU (1) | AU2013245452C1 (ro) |
| BR (1) | BR102013028259A2 (ro) |
| CA (1) | CA2831289C (ro) |
| CY (1) | CY1116253T1 (ro) |
| DK (1) | DK2730562T3 (ro) |
| EA (1) | EA027080B1 (ro) |
| ES (1) | ES2539618T3 (ro) |
| FR (1) | FR2997696B1 (ro) |
| GE (1) | GEP20156308B (ro) |
| HR (1) | HRP20150570T1 (ro) |
| HU (1) | HUE026525T2 (ro) |
| JO (1) | JO3189B1 (ro) |
| MA (1) | MA35147B1 (ro) |
| MD (1) | MD4392C1 (ro) |
| ME (1) | ME02120B (ro) |
| MX (1) | MX355590B (ro) |
| MY (1) | MY159701A (ro) |
| NZ (1) | NZ616768A (ro) |
| PL (1) | PL2730562T3 (ro) |
| PT (1) | PT2730562E (ro) |
| RS (1) | RS53993B1 (ro) |
| SA (1) | SA113350005B1 (ro) |
| SG (1) | SG2013077235A (ro) |
| SI (1) | SI2730562T1 (ro) |
| TW (1) | TWI488833B (ro) |
| UA (1) | UA118008C2 (ro) |
| UY (1) | UY35108A (ro) |
| WO (1) | WO2014072640A1 (ro) |
| ZA (1) | ZA201308001B (ro) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3101010A1 (en) | 2015-06-03 | 2016-12-07 | Urquima S.A. | New method for the preparation of highly pure ivabradine base and salts thereof |
| CN105541605A (zh) * | 2016-02-04 | 2016-05-04 | 扬州大学 | 一种轴手性联萘配体前体(s)-2,2’-二羧酸-1,1’-联萘的合成方法 |
| KR20250047840A (ko) | 2017-08-31 | 2025-04-04 | 다이이찌 산쿄 가부시키가이샤 | 항체-약물 콘주게이트의 신규 제조 방법 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5310598B2 (ro) * | 1972-01-28 | 1978-04-14 | ||
| JPH0753692B2 (ja) * | 1990-10-30 | 1995-06-07 | 工業技術院長 | 芳香族カルボン酸エステル類の製造方法 |
| FR2681862B1 (fr) * | 1991-09-27 | 1993-11-12 | Adir Cie | Nouvelles (benzocycloalkyl)alkylamines, leur procede de preparation, et les compositions pharmaceutiques qui les contiennent. |
| DE4333711A1 (de) * | 1993-10-02 | 1995-04-06 | Hoechst Ag | 2,4,5-Trihalogenzimtsäurenitrile und Verfahren zu ihrer Herstellung |
| DE10159270A1 (de) * | 2001-12-03 | 2003-06-12 | Bayer Ag | Verfahren zur Arylierung von Olefinen |
| WO2005123662A1 (en) * | 2004-06-18 | 2005-12-29 | Janssen Pharmaceutica N.V. | Modified heck reaction |
| CN101407474B (zh) * | 2008-11-18 | 2011-12-14 | 东华大学 | 一种2-溴-4,5-二甲氧基苯丙腈的制备方法 |
| WO2011138825A1 (ja) | 2010-05-06 | 2011-11-10 | 株式会社島津製作所 | 材料試験機 |
| HUP1000245A2 (en) * | 2010-05-07 | 2011-11-28 | Richter Gedeon Nyrt | Industrial process for the production ivabradin salts |
| CN102464595B (zh) * | 2010-11-17 | 2015-02-25 | 山东新时代药业有限公司 | 一种伊伐布雷定中间体的合成方法 |
-
2012
- 2012-11-08 FR FR1260576A patent/FR2997696B1/fr not_active Expired - Fee Related
-
2013
- 2013-10-15 AU AU2013245452A patent/AU2013245452C1/en not_active Ceased
- 2013-10-16 MY MYPI2013701948A patent/MY159701A/en unknown
- 2013-10-17 NZ NZ616768A patent/NZ616768A/en not_active IP Right Cessation
- 2013-10-17 SG SG2013077235A patent/SG2013077235A/en unknown
- 2013-10-24 CA CA2831289A patent/CA2831289C/en not_active Expired - Fee Related
- 2013-10-24 JO JOP/2013/0312A patent/JO3189B1/ar active
- 2013-10-29 TW TW102139148A patent/TWI488833B/zh not_active IP Right Cessation
- 2013-10-29 UY UY0001035108A patent/UY35108A/es not_active Application Discontinuation
- 2013-10-29 ZA ZA2013/08001A patent/ZA201308001B/en unknown
- 2013-10-30 MD MDA20130082A patent/MD4392C1/ro not_active IP Right Cessation
- 2013-11-01 BR BR102013028259-6A patent/BR102013028259A2/pt not_active Application Discontinuation
- 2013-11-04 MA MA36388A patent/MA35147B1/fr unknown
- 2013-11-04 MX MX2013012858A patent/MX355590B/es active IP Right Grant
- 2013-11-05 GE GEAP201313282A patent/GEP20156308B/en unknown
- 2013-11-05 KR KR1020130133365A patent/KR20140059731A/ko not_active Ceased
- 2013-11-06 SA SA113350005A patent/SA113350005B1/ar unknown
- 2013-11-06 AR ARP130104055A patent/AR093373A1/es unknown
- 2013-11-06 US US14/073,213 patent/US8779122B2/en not_active Expired - Fee Related
- 2013-11-07 HU HUE13191850A patent/HUE026525T2/en unknown
- 2013-11-07 PL PL13191850T patent/PL2730562T3/pl unknown
- 2013-11-07 EA EA201301136A patent/EA027080B1/ru not_active IP Right Cessation
- 2013-11-07 ES ES13191850.0T patent/ES2539618T3/es active Active
- 2013-11-07 CN CN201310548260.8A patent/CN103804225B/zh not_active Expired - Fee Related
- 2013-11-07 JP JP2013230752A patent/JP6058519B2/ja active Active
- 2013-11-07 PT PT131918500T patent/PT2730562E/pt unknown
- 2013-11-07 RS RS20150297A patent/RS53993B1/sr unknown
- 2013-11-07 DK DK13191850.0T patent/DK2730562T3/en active
- 2013-11-07 UA UAA201312954A patent/UA118008C2/uk unknown
- 2013-11-07 WO PCT/FR2013/052653 patent/WO2014072640A1/fr not_active Ceased
- 2013-11-07 SI SI201330038T patent/SI2730562T1/sl unknown
- 2013-11-07 ME MEP-2015-74A patent/ME02120B/me unknown
- 2013-11-07 EP EP13191850.0A patent/EP2730562B1/fr active Active
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2015
- 2015-05-07 CY CY20151100400T patent/CY1116253T1/el unknown
- 2015-05-28 HR HRP20150570TT patent/HRP20150570T1/hr unknown
- 2015-11-02 JP JP2015215831A patent/JP2016047837A/ja not_active Withdrawn
Also Published As
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| WO2014069875A3 (ko) | 아세트아미노펜의 신규한 제조방법 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FG4A | Patent for invention issued | ||
| KA4A | Patent for invention lapsed due to non-payment of fees (with right of restoration) | ||
| MM4A | Patent for invention definitely lapsed due to non-payment of fees |