CA2631832C - Improved process for the preparation of 4-(benzimidazolylmethylamino)-benzamides and the salts thereof - Google Patents

Improved process for the preparation of 4-(benzimidazolylmethylamino)-benzamides and the salts thereof Download PDF

Info

Publication number
CA2631832C
CA2631832C CA2631832A CA2631832A CA2631832C CA 2631832 C CA2631832 C CA 2631832C CA 2631832 A CA2631832 A CA 2631832A CA 2631832 A CA2631832 A CA 2631832A CA 2631832 C CA2631832 C CA 2631832C
Authority
CA
Canada
Prior art keywords
formula
water
group
denotes
ethanol
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
Application number
CA2631832A
Other languages
English (en)
French (fr)
Other versions
CA2631832A1 (en
Inventor
Georg Zerban
Arndt Hausherr
Rainer Hamm
Gunter Koch
Kerstin Schlarb
Heinz-Peter Schmitt
Bjoern Weyell
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Boehringer Ingelheim International GmbH
Original Assignee
Boehringer Ingelheim International GmbH
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 Boehringer Ingelheim International GmbH filed Critical Boehringer Ingelheim International GmbH
Publication of CA2631832A1 publication Critical patent/CA2631832A1/en
Application granted granted Critical
Publication of CA2631832C publication Critical patent/CA2631832C/en
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
    • C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
    • C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
    • C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
    • C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
    • C07D271/07—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
    • 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
    • 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
    • C07D401/02—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 two hetero rings
    • C07D401/12—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 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
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (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)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
CA2631832A 2005-12-21 2006-12-20 Improved process for the preparation of 4-(benzimidazolylmethylamino)-benzamides and the salts thereof Expired - Fee Related CA2631832C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE102005061623A DE102005061623A1 (de) 2005-12-21 2005-12-21 Verbessertes Verfahren zur Herstellung von 4-(Benzimidazolylmethylamino)-Benzamidinen und deren Salzen
DE102005061623.2 2005-12-21
PCT/EP2006/070033 WO2007071742A1 (en) 2005-12-21 2006-12-20 Improved process for the preparation of 4-(benzimidazolylmethylamino)-benzamides and the salts thereof

Publications (2)

Publication Number Publication Date
CA2631832A1 CA2631832A1 (en) 2007-06-28
CA2631832C true CA2631832C (en) 2014-04-15

Family

ID=37945425

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2631832A Expired - Fee Related CA2631832C (en) 2005-12-21 2006-12-20 Improved process for the preparation of 4-(benzimidazolylmethylamino)-benzamides and the salts thereof

Country Status (16)

Country Link
US (2) US20070185333A1 (enExample)
EP (1) EP1966171A1 (enExample)
JP (1) JP5317701B2 (enExample)
KR (1) KR101408709B1 (enExample)
CN (1) CN101346360A (enExample)
AR (1) AR058570A1 (enExample)
AU (1) AU2006326979B2 (enExample)
BR (1) BRPI0620204A2 (enExample)
CA (1) CA2631832C (enExample)
DE (1) DE102005061623A1 (enExample)
IL (1) IL192241A (enExample)
NZ (1) NZ569851A (enExample)
RU (1) RU2455292C2 (enExample)
TW (1) TWI391382B (enExample)
WO (1) WO2007071742A1 (enExample)
ZA (1) ZA200804030B (enExample)

Families Citing this family (34)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030181488A1 (en) 2002-03-07 2003-09-25 Boehringer Ingelheim Pharma Gmbh & Co. Kg Administration form for the oral application of 3-[(2-{[4-(hexyloxycarbonylamino-imino-methyl)-phenylamino]-methyl}-1-methyl-1H-benzimidazol-5-carbonyl)-pyridin-2-yl-amino]-propionic acid ethyl ester and the salts thereof
DE10339862A1 (de) * 2003-08-29 2005-03-24 Boehringer Ingelheim Pharma Gmbh & Co. Kg 3-[(2-{[4-(Hexyloxycarbonylamino-imino-methyl)- phenylamino]-methyl}-1-methyl-1H-benzimidazol-5-carbonyl)-pyridin-2-yl-amino]-propionsäure-ethylester-Methansulfonat und dessen Verwendung als Arzneimittel
DE102005061624A1 (de) * 2005-12-21 2007-06-28 Boehringer Ingelheim Pharma Gmbh & Co. Kg Verbessertes Verfahren zur Herstellung von Salzen von 4-(Benzimidazolylmethylamino)-Benzamidinen
DE102006054005A1 (de) * 2006-11-16 2008-05-21 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue Polymorphe von 3-[(2-{[4-(Hexyloxycarbonylamino-imino-methyl)-phenylamino]-methyl}-1-methyl-1H-benzimidazol-5-carbonyl)-pyridin-2-yl-amino]-propionsäure-ethylester
CZ305085B6 (cs) 2008-03-14 2015-04-29 Zentiva, K.S. Způsob přípravy dabigatranu
AU2009228795B2 (en) * 2008-03-28 2014-02-13 Boehringer Ingelheim International Gmbh Process for preparing orally administered dabigatran formulations
HUE025533T2 (en) * 2008-06-16 2016-05-30 Boehringer Ingelheim Int A process for preparing an intermediate of dabigatran etexylate
BRPI0915942A2 (pt) * 2008-07-14 2019-04-09 Boehringer Ingelheim International Gmbh método para produção de compostos medicinais contendo dabigatrana
CZ2008669A3 (cs) * 2008-10-24 2010-05-05 Zentiva, A. S. Zpusob prípravy dabigatranu a jeho meziprodukty
BRPI0921479A2 (pt) 2008-11-11 2016-01-12 Boehringer Ingelheim Int método para tratamento ou prevenção de trombose usando etexilato de dabigatran ou um sal do mesmo com aprimorado perfil de segurança em relação à terapia convencional com varfarina
US8399678B2 (en) * 2009-11-18 2013-03-19 Boehringer Ingelheim International Gmbh Process for the manufacture of dabigatran etexilate
HUP1000069A2 (en) * 2010-02-02 2012-05-02 Egis Gyogyszergyar Nyilvanosan M Kod Ruszvunytarsasag New salts for the preparation of pharmaceutical composition
EP2649060B1 (en) 2010-12-06 2017-04-05 MSN Laboratories Limited Process for the preparation of benzimidazole derivatives and its salts
EP2522662A1 (en) * 2011-05-11 2012-11-14 Medichem, S.A. Dabigatran etexilate and related substances, processes and compositions, and use of the substances as reference standards and markers
HUP1100244A2 (hu) 2011-05-11 2012-11-28 Egis Gyogyszergyar Nyilvanosan Muekoedoe Reszvenytarsasag Gyógyszeripari intermedierek és eljárás elõállításukra
CN102993175B (zh) * 2011-09-08 2014-08-13 天津药物研究院 达比加群的酯衍生物及其制备方法和用途
US9212166B2 (en) 2012-01-20 2015-12-15 Cadila Healthcare Limited Process for the preparation of dabigatran etexilate mesylate and polymorphs of intermediates thereof
EP2631234A1 (en) 2012-02-23 2013-08-28 Esteve Química, S.A. Solid forms of dabigatran etexilate mesylate and processes for their preparation
WO2013150545A2 (en) 2012-04-02 2013-10-10 Msn Laboratories Limited Process for the preparation of benzimidazole derivatives and salts thereof
CN102850327B (zh) * 2012-06-19 2014-07-16 上海现代制药股份有限公司 一种制备达比加群酯的中间体及其制备方法和应用
CN102850325B (zh) * 2012-06-19 2014-03-26 上海现代制药海门有限公司 一种达比加群酯关键中间体的制备方法
CN102850326B (zh) * 2012-06-19 2014-04-09 上海现代制药股份有限公司 一种达比加群酯中间体及其制备方法和应用
EP2872500A4 (en) * 2012-07-12 2016-03-30 Rao Davuluri Ramamohan IMPROVED METHOD FOR THE PRODUCTION OF DABIGATRANETEXILATE MESYLATE AND INTERMEDIATE PRODUCTS THEREOF
CA2881947A1 (en) * 2012-08-31 2014-03-06 Ranbaxy Laboratories Limited Process for the preparation of crystalline form i of methanesulfonate salt of dabigatran etexilate
WO2014068587A2 (en) * 2012-10-29 2014-05-08 Biophore India Pharmaceuticals Pvt. Ltd. An improved process for the synthesis of dabigatran and its intermediates
US10077251B2 (en) 2012-10-29 2018-09-18 Biophore India Pharmaceuticals Pvt. Ltd. Process for the synthesis of Dabigatran Etexilate and its intermediates
WO2014151929A1 (en) 2013-03-15 2014-09-25 Proteus Digital Health, Inc. Personal authentication apparatus system and method
EP2835370A1 (en) 2013-08-08 2015-02-11 Medichem, S.A. New crystals of dabigatran etexilate mesylate
CN104031031B (zh) * 2014-05-05 2017-01-11 南通常佑药业科技有限公司 一种制备达比加群酯的方法
CN103992241B (zh) * 2014-06-05 2016-08-24 雅本化学股份有限公司 N-取代苯基甘氨酸的制备方法
CN105461686A (zh) * 2014-08-25 2016-04-06 江苏豪森药业股份有限公司 制备高纯度甲磺酸达比加群酯晶型的方法
WO2016046157A1 (de) 2014-09-24 2016-03-31 Bayer Pharma Aktiengesellschaft Faktor xia hemmende pyridobenzazepin- und pyridobenzazocin-derivate
CN111253369A (zh) * 2018-11-30 2020-06-09 上海医药集团股份有限公司 一种苯磺酸盐、其制备方法及其在制备达比加群酯中的应用
CN111595828B (zh) * 2019-02-21 2022-10-14 香港科技大学深圳研究院 一种纳米氧化锌溶出的监测方法

Family Cites Families (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6087380A (en) * 1949-11-24 2000-07-11 Boehringer Ingelheim Pharma Kg Disubstituted bicyclic heterocycles, the preparations and the use thereof as pharmaceutical compositions
PE121699A1 (es) 1997-02-18 1999-12-08 Boehringer Ingelheim Pharma Heterociclos biciclicos disustituidos como inhibidores de la trombina
TWI248435B (en) * 1998-07-04 2006-02-01 Boehringer Ingelheim Pharma Benzimidazoles, the preparation thereof and their use as pharmaceutical compositions
US6248770B1 (en) * 1998-07-09 2001-06-19 Boehringer Ingelheim Pharma Kg Benzimidazoles having antithrombotic activity
DE19962329A1 (de) * 1999-12-23 2001-06-28 Boehringer Ingelheim Pharma Benzimidazole, deren Herstellung und deren Verwendung als Arzneimittel
US6451832B2 (en) * 1999-12-23 2002-09-17 Boehringer Ingelheim Pharma Kg Benzimidazoles with antithrombotic activity
EA009664B1 (ru) * 2002-03-07 2008-02-28 Бёрингер Ингельхайм Фарма Гмбх Унд Ко. Кг Предназначенная для перорального применения лекарственная форма для этилового эфира 3-[(2-{[4-(гексилоксикарбониламиноиминометил)фениламино]метил}-1-метил-1h-бензимидазол-5-карбонил)пиридин-2-иламино]пропионовой кислоты и его солей
EP1609784A1 (de) * 2004-06-25 2005-12-28 Boehringer Ingelheim Pharma GmbH & Co.KG Verfahren zur Herstellung von 4-(Benzimidazolylmethylamino)-Benzamidinen
DE102005061624A1 (de) 2005-12-21 2007-06-28 Boehringer Ingelheim Pharma Gmbh & Co. Kg Verbessertes Verfahren zur Herstellung von Salzen von 4-(Benzimidazolylmethylamino)-Benzamidinen
EP1956018A1 (de) 2007-02-06 2008-08-13 Boehringer Ingelheim Pharma GmbH & Co. KG Verfahren zur Herstellung eines Benzimidazolderivats
US20120276206A1 (en) 2008-03-28 2012-11-01 Boehringer Ingelheim International Gmbh Method for manufacturing acid pellets
AU2009228795B2 (en) 2008-03-28 2014-02-13 Boehringer Ingelheim International Gmbh Process for preparing orally administered dabigatran formulations
WO2009153214A1 (en) 2008-06-16 2009-12-23 Boehringer Ingelheim International Gmbh Process for the manufacture of an intermediate in the synthesis of dabigatran
HUE025533T2 (en) 2008-06-16 2016-05-30 Boehringer Ingelheim Int A process for preparing an intermediate of dabigatran etexylate
BRPI0915942A2 (pt) 2008-07-14 2019-04-09 Boehringer Ingelheim International Gmbh método para produção de compostos medicinais contendo dabigatrana

Also Published As

Publication number Publication date
IL192241A0 (en) 2008-12-29
AU2006326979A1 (en) 2007-06-28
AR058570A1 (es) 2008-02-13
TW200804302A (en) 2008-01-16
AU2006326979B2 (en) 2013-03-28
RU2008129376A (ru) 2010-01-27
WO2007071742A1 (en) 2007-06-28
IL192241A (en) 2014-01-30
KR101408709B1 (ko) 2014-06-17
NZ569851A (en) 2011-10-28
US20100210845A1 (en) 2010-08-19
BRPI0620204A2 (pt) 2011-11-01
US8354543B2 (en) 2013-01-15
RU2455292C2 (ru) 2012-07-10
CN101346360A (zh) 2009-01-14
CA2631832A1 (en) 2007-06-28
JP5317701B2 (ja) 2013-10-16
DE102005061623A1 (de) 2007-06-28
KR20080077029A (ko) 2008-08-20
ZA200804030B (en) 2009-02-25
JP2009520765A (ja) 2009-05-28
EP1966171A1 (en) 2008-09-10
US20070185333A1 (en) 2007-08-09
TWI391382B (zh) 2013-04-01

Similar Documents

Publication Publication Date Title
CA2631832C (en) Improved process for the preparation of 4-(benzimidazolylmethylamino)-benzamides and the salts thereof
CA2632310C (en) Improved process for the preparation of the salts of 4-(benzimidazolylmethylamino)-benzamides
CA2570499C (en) Method for producing 4-(benzimidazolylmethylamino)-benzamidines
MX2008007170A (en) Improved process for the preparation of the salts of 4-(benzimidazolylmethylamino)-benzamides

Legal Events

Date Code Title Description
EEER Examination request
MKLA Lapsed

Effective date: 20151221