MD4392C1 - 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

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Publication number
MD4392C1
MD4392C1 MDA20130082A MD20130082A MD4392C1 MD 4392 C1 MD4392 C1 MD 4392C1 MD A20130082 A MDA20130082 A MD A20130082A MD 20130082 A MD20130082 A MD 20130082A MD 4392 C1 MD4392 C1 MD 4392C1
Authority
MD
Moldova
Prior art keywords
synthesis
enenitrile
ivabradine
dimethoxyphenyl
prop
Prior art date
Application number
MDA20130082A
Other languages
English (en)
Russian (ru)
Other versions
MD20130082A2 (ro
MD4392B1 (ro
Inventor
Мария дель Пилар КАРРАНСА
АРАНДА Мария Изабель ГАРСИЯ
Жозе Лоренсо ГОНСАЛЕС
Фредерик Санчес
Original Assignee
Les Laboratoires Servier
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Les Laboratoires Servier filed Critical Les Laboratoires Servier
Publication of MD20130082A2 publication Critical patent/MD20130082A2/ro
Publication of MD4392B1 publication Critical patent/MD4392B1/ro
Publication of MD4392C1 publication Critical patent/MD4392C1/ro

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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

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (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.
MDA20130082A 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 MD4392C1 (ro)

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 MD4392B1 (ro) 2016-01-31
MD4392C1 true 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 (36)

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)
HK (2) HK1193408A1 (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 (2)

* Cited by examiner, † Cited by third party
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

Citations (5)

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Publication number Priority date Publication date Assignee Title
DE2303919A1 (de) * 1972-01-28 1973-08-02 Nisshin Flour Milling Co Verfahren zur herstellung von benzylpyrimidinderivaten
EP0534859A1 (fr) * 1991-09-27 1993-03-31 Adir Et Compagnie 3-Benzazépin-zones substituées par un groupe benzocyclobutyl- ou indanyl-alkyl-amino-alkyle, utiles dans le traitement des affections cardiovasculaires
WO2005123662A1 (en) * 2004-06-18 2005-12-29 Janssen Pharmaceutica N.V. Modified heck reaction
CN101407474A (zh) * 2008-11-18 2009-04-15 东华大学 一种2-溴-4,5-二甲氧基苯丙腈的制备方法
WO2011138625A1 (en) * 2010-05-07 2011-11-10 Richter Gedeon Nyrt. Industrial process for the synthesis of ivabradine salts

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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
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
CN102884410B (zh) 2010-05-06 2015-05-27 株式会社岛津制作所 材料试验机
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

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2303919A1 (de) * 1972-01-28 1973-08-02 Nisshin Flour Milling Co Verfahren zur herstellung von benzylpyrimidinderivaten
EP0534859A1 (fr) * 1991-09-27 1993-03-31 Adir Et Compagnie 3-Benzazépin-zones substituées par un groupe benzocyclobutyl- ou indanyl-alkyl-amino-alkyle, utiles dans le traitement des affections cardiovasculaires
WO2005123662A1 (en) * 2004-06-18 2005-12-29 Janssen Pharmaceutica N.V. Modified heck reaction
CN101407474A (zh) * 2008-11-18 2009-04-15 东华大学 一种2-溴-4,5-二甲氧基苯丙腈的制备方法
WO2011138625A1 (en) * 2010-05-07 2011-11-10 Richter Gedeon Nyrt. Industrial process for the synthesis of ivabradine salts

Non-Patent Citations (5)

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Kametani T., Ogasawara K., Takasashi T. Studies of the syntheses of heterocyclic compounds - CDXCIV: A total synthesis of (±)-xylopinine by thermolysis. Tetrahedron 1973, v. 29, p. 73-76 *
Kenneth D. Paull, Cheng C. C. Facile synthesis of 4-substituted 3a,4,5,9b-tetrahydrobenz[e]isoindoline. The Journal of Organic Chemistry, 1972, vol. 37 (21), p. 3374-3376 *
Tetsuji Kametani, Hirotaka Yukawa, Yukio Suzuki, Toshio Honda. Synthesis of (±)-tetrahydropalmatine and spirobenzylisoquinolines by thermolysis of benzocyclobutene derivatives. Journal of the Chemical Society, Perkin Transactions 1, 1985, p. 2151-2154 *
Toshio Honda, Koji Ueda, Masayoshi Tsubuki, Tetsuya Toya, Akira Kurozumi. A novel synthesis of cyclobutane sesquiterpenes, (±)-italicene and (±)isoitalicene. Journal of the Chemical Society, Perkin Transactions 1, 1991, p. 1749-1754 *
Zhao Sheng Yin, Liang Hong Yu, Shao Zhi Yu, Chen Rui. A practical synthesis of 1-cyano-4,5-dimethoxybenzocyclobutene. Journal of Chemical Research, 2009, nr. 7, p. 420-422 *

Also Published As

Publication number Publication date
UA118008C2 (uk) 2018-11-12
SI2730562T1 (sl) 2015-07-31
PL2730562T3 (pl) 2015-08-31
ES2539618T3 (es) 2015-07-02
HRP20150570T1 (en) 2015-07-03
AU2013245452B2 (en) 2017-02-16
ME02120B (me) 2015-10-20
JP6058519B2 (ja) 2017-01-11
MA35147B1 (fr) 2014-06-02
UY35108A (es) 2014-05-30
JP2014114275A (ja) 2014-06-26
EP2730562B1 (fr) 2015-03-25
JO3189B1 (ar) 2018-03-08
AU2013245452C1 (en) 2017-06-22
KR20140059731A (ko) 2014-05-16
MY159701A (en) 2017-01-13
NZ616768A (en) 2015-02-27
PT2730562E (pt) 2015-05-20
CY1116253T1 (el) 2017-02-08
AU2013245452A1 (en) 2014-05-22
AR093373A1 (es) 2015-06-03
CN103804225A (zh) 2014-05-21
TWI488833B (zh) 2015-06-21
CN103804225B (zh) 2016-02-17
CA2831289A1 (en) 2014-05-08
SG2013077235A (en) 2014-06-27
CA2831289C (en) 2016-02-09
MX2013012858A (es) 2014-08-07
EA027080B1 (ru) 2017-06-30
EA201301136A2 (ru) 2014-05-30
WO2014072640A1 (fr) 2014-05-15
MX355590B (es) 2018-04-24
EP2730562A1 (fr) 2014-05-14
GEP20156308B (en) 2015-06-25
RS53993B1 (en) 2015-10-30
BR102013028259A2 (pt) 2014-10-07
MD20130082A2 (ro) 2014-05-31
JP2016047837A (ja) 2016-04-07
FR2997696A1 (fr) 2014-05-09
EA201301136A3 (ru) 2014-07-30
FR2997696B1 (fr) 2014-12-05
DK2730562T3 (en) 2015-06-29
ZA201308001B (en) 2014-07-30
SA113350005B1 (ar) 2015-12-06
HUE026525T2 (en) 2016-06-28
TW201418197A (zh) 2014-05-16
MD4392B1 (ro) 2016-01-31
US8779122B2 (en) 2014-07-15
HK1193408A1 (en) 2014-09-19
HK1198159A1 (zh) 2015-03-13
US20140128598A1 (en) 2014-05-08

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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