EA200900834A1 - Новый способ получения функционализированных бензоциклобутенов и их применение в синтезе ивабрадина и его аддитивных солей с фармацевтически приемлемой кислотой - Google Patents

Новый способ получения функционализированных бензоциклобутенов и их применение в синтезе ивабрадина и его аддитивных солей с фармацевтически приемлемой кислотой

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EA200900834A1
EA200900834A1 EA200900834A EA200900834A EA200900834A1 EA 200900834 A1 EA200900834 A1 EA 200900834A1 EA 200900834 A EA200900834 A EA 200900834A EA 200900834 A EA200900834 A EA 200900834A EA 200900834 A1 EA200900834 A1 EA 200900834A1
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EA
Eurasian Patent Office
Prior art keywords
group
branched
linear
synthesis
ivabradin
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EA200900834A
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English (en)
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EA017503B1 (ru
Inventor
Жан-Луи Пегльон
Оливье Бодуан
Никола Одик
Манон Шомонте
Рикардо Пиккарди
Original Assignee
Ле Лаборатуар Сервье
Сантр Насьональ Де Ля Решерш Сьентифик
Университе Клод Бернар Лион 1
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Publication of EA200900834A1 publication Critical patent/EA200900834A1/ru
Publication of EA017503B1 publication Critical patent/EA017503B1/ru

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/093—Preparation of carboxylic acids or their salts, halides or anhydrides by hydrolysis of —CX3 groups, X being halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
    • C07C51/377—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups
    • C07C51/38—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups by decarboxylation
    • 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
    • A61P9/10—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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B37/00—Reactions without formation or introduction of functional groups containing hetero atoms, involving either the formation of a carbon-to-carbon bond between two carbon atoms not directly linked already or the disconnection of two directly linked carbon atoms
    • C07B37/10—Cyclisation
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/42—Separation; Purification; Stabilisation; Use of additives
    • C07C51/50—Use of additives, e.g. for stabilisation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C61/00—Compounds having carboxyl groups bound to carbon atoms of rings other than six-membered aromatic rings
    • C07C61/16—Unsaturated compounds
    • C07C61/39—Unsaturated compounds containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C62/00—Compounds having carboxyl groups bound to carbon atoms of rings other than six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C62/30—Unsaturated compounds
    • C07C62/34—Unsaturated compounds containing ether groups, groups, groups, or groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/317—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/317—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups
    • C07C67/32—Decarboxylation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/74—Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring
    • C07C69/753—Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring of polycyclic acids
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/74—Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring
    • C07C69/757—Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
    • C—CHEMISTRY; METALLURGY
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    • 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
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    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
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    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
    • C07C2602/14—All rings being cycloaliphatic
    • C07C2602/22—All rings being cycloaliphatic the ring system containing eight carbon atoms, e.g. pentalene

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Health & Medical Sciences (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Cardiology (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • General Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Hospice & Palliative Care (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)

Abstract

Способ получения соединений формулы (IV):где R, R, Rи R, которые могут быть идентичными или различными, каждыйпредставляет собой атом водорода, линейную или разветвленную (С-С)алкильнуюгруппу, линейную или разветвленную (С-С)алкоксигруппу, атом фтора, атом хлора,защищенную аминогруппу, защищенную гидроксильную группу,алкоксикарбонильную группу, в которой алкоксильная группа является линейной илиразветвленной (C-С), или CFгруппу, или R=R=H и Rи Rвместе с несущими ихатомами углерода образуют группу 1,3-диоксолана,Rпредставляет собой насыщенную или ненасыщенную, линейную или разветвленную(С-С)алкильную группу, линейную или разветвленную (С-С)гидроксиалкильную группу, в которой гидроксильная группа является защищенной, или CORгруппу, вкоторой Rпредставляет собой линейную или разветвленную (С-С)алкильную группу, Rпредставляет собой группу циано или CORгруппу, в которой Rявляется линейной или разветвленной (С-С)алкильной группой, Применение в синтезе ивабрадина, его аддитивных солей с фармацевтически приемлемой кислотой и их гидратов.
EA200900834A 2008-07-17 2009-07-16 Новый способ получения функционализированных бензоциклобутенов и их применение в синтезе ивабрадина и его аддитивных солей с фармацевтически приемлемой кислотой EA017503B1 (ru)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
FR0804061A FR2933975B1 (fr) 2008-07-17 2008-07-17 Nouveau procede de preparation de benzocyclobutenes fonctionnalises,et application a la synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable.

Publications (2)

Publication Number Publication Date
EA200900834A1 true EA200900834A1 (ru) 2010-02-26
EA017503B1 EA017503B1 (ru) 2013-01-30

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EA200900834A EA017503B1 (ru) 2008-07-17 2009-07-16 Новый способ получения функционализированных бензоциклобутенов и их применение в синтезе ивабрадина и его аддитивных солей с фармацевтически приемлемой кислотой

Country Status (20)

Country Link
US (2) US8110701B2 (ru)
EP (1) EP2145871A1 (ru)
JP (1) JP5236588B2 (ru)
KR (1) KR101119336B1 (ru)
CN (1) CN101628872B (ru)
AR (1) AR074705A1 (ru)
AU (1) AU2009202740B2 (ru)
BR (1) BRPI0902392A2 (ru)
CA (1) CA2671932C (ru)
EA (1) EA017503B1 (ru)
FR (1) FR2933975B1 (ru)
GE (1) GEP20115343B (ru)
HK (1) HK1140186A1 (ru)
MA (1) MA31149B1 (ru)
MX (1) MX2009007492A (ru)
MY (1) MY148930A (ru)
NZ (1) NZ578445A (ru)
SG (2) SG158799A1 (ru)
WO (1) WO2010007253A2 (ru)
ZA (1) ZA200904944B (ru)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008146308A2 (en) 2007-05-30 2008-12-04 Ind-Swift Laboratories Limited Process for the preparation of ivabradine hydrochloride and polymorph thereof
CN101671265B (zh) * 2008-09-12 2012-08-15 中国科学院上海药物研究所 一种苯并环丁烷类化合物及其制备方法与用途
CN101774969B (zh) * 2009-01-13 2012-07-04 江苏恒瑞医药股份有限公司 硫酸伊伐布雷定及其i型结晶的制备方法
SI23290A (sl) 2010-02-12 2011-08-31 Krka D.D., Novo Mesto Nove oblike ivabradin hidroklorida
HUP1000245A2 (en) * 2010-05-07 2011-11-28 Richter Gedeon Nyrt Industrial process for the production ivabradin salts
BR112013001430B1 (pt) 2010-07-20 2018-02-06 Bayer Cropscience Ag Compostos, composição fungicida e método para controle de fungos fitopatogênicos de culturas
FR2971507B1 (fr) * 2011-02-14 2013-01-18 Servier Lab Nouveau procede de synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable
FR2984319B1 (fr) * 2011-12-20 2013-12-27 Servier Lab Nouveau procede de synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable
FR2986804A1 (fr) * 2012-02-09 2013-08-16 Servier Lab Procede de synthese enzymatique de l'acide (7s) 3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-triene 7-carboxylique ou de ses esters, et application a la synthese de l'ivabradine et de ses sels
CN102649749A (zh) * 2012-04-05 2012-08-29 中国药科大学 制备苯并环丁烷类化合物的方法及其衍生物
FR3005658B1 (fr) * 2013-05-17 2015-04-24 Servier Lab "procede de synthese du 3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-triene-7-carbonitrile, et application a la synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable"
EP3101010A1 (en) 2015-06-03 2016-12-07 Urquima S.A. New method for the preparation of highly pure ivabradine base and salts thereof
MX2020007994A (es) 2018-02-02 2020-09-09 Boehringer Ingelheim Int Derivados de triazolopirimidina para usar como inhibidores de ghrelin o-aciltransferasa (goat).
CR20200332A (es) 2018-02-02 2020-09-03 Boehringer Ingelheim Int Derivados de oxadiazolopiridina sustitidos con bencilo, (piridin-3-il)metilo o (piridin-4-il)metilo como inhibidores de ghrelin o-aciltransferasa (goat)
EP4153600A1 (en) 2020-05-22 2023-03-29 Boehringer Ingelheim International GmbH Continuous process for manufacturing alkyl 7-amino-5-methyl-[1,2,5]oxadiazolo[3,4-b]pyridine-carboxylate
JP2023526351A (ja) 2020-05-22 2023-06-21 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 アルキル７－アミノ－５－メチル－［１，２，５］オキサジアゾロ［３，４－ｂ］ピリジンカルボキシレートの製造方法

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Also Published As

Publication number Publication date
CN101628872B (zh) 2013-04-17
CN101628872A (zh) 2010-01-20
MA31149B1 (fr) 2010-02-01
AR074705A1 (es) 2011-02-09
BRPI0902392A2 (pt) 2010-04-20
KR20100009487A (ko) 2010-01-27
CA2671932C (fr) 2012-09-11
HK1140186A1 (en) 2010-10-08
GEP20115343B (en) 2011-12-12
ZA200904944B (en) 2010-05-26
SG185927A1 (en) 2012-12-28
FR2933975A1 (fr) 2010-01-22
MY148930A (en) 2013-06-14
FR2933975B1 (fr) 2011-02-18
US8110701B2 (en) 2012-02-07
JP2010047563A (ja) 2010-03-04
US8288581B2 (en) 2012-10-16
EP2145871A1 (fr) 2010-01-20
EA017503B1 (ru) 2013-01-30
KR101119336B1 (ko) 2012-03-07
AU2009202740A1 (en) 2010-02-04
WO2010007253A3 (fr) 2010-03-25
WO2010007253A2 (fr) 2010-01-21
US20100016580A1 (en) 2010-01-21
AU2009202740B2 (en) 2012-10-11
NZ578445A (en) 2011-01-28
CA2671932A1 (fr) 2010-01-17
MX2009007492A (es) 2010-03-01
US20120116112A1 (en) 2012-05-10
SG158799A1 (en) 2010-02-26
JP5236588B2 (ja) 2013-07-17

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