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AR080149A1 - Procedimiento para la preparacion del nevibolol - Google Patents

Procedimiento para la preparacion del nevibolol

Info

Publication number
AR080149A1
AR080149A1 ARP110100405A ARP110100405A AR080149A1 AR 080149 A1 AR080149 A1 AR 080149A1 AR P110100405 A ARP110100405 A AR P110100405A AR P110100405 A ARP110100405 A AR P110100405A AR 080149 A1 AR080149 A1 AR 080149A1
Authority
AR
Argentina
Prior art keywords
methyl
mixture
butanol
bis
mixed
Prior art date
Application number
ARP110100405A
Other languages
English (en)
Inventor
Sandra Bartoli
Amalia Cipollone
Daniela Fattori
Original Assignee
Menarini Internat Operation Luxembourg S A
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 Menarini Internat Operation Luxembourg S A filed Critical Menarini Internat Operation Luxembourg S A
Publication of AR080149A1 publication Critical patent/AR080149A1/es

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D407/00Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/02Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
    • C07D407/12Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/12Antihypertensives
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D311/00Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/58Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D311/00Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/58Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
    • C07D311/60Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with aryl radicals attached in position 2

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyrane Compounds (AREA)
  • Epoxy Compounds (AREA)
  • Steroid Compounds (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Peptides Or Proteins (AREA)
  • Saccharide Compounds (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Treatment Of Liquids With Adsorbents In General (AREA)
  • Treating Waste Gases (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

Abstract

REIVINDICACION 1: 1. Procedimiento para la preparacion del compuesto Nebivolol en forma de mezcla racémica de dos enantiomeros [2S[2R[R[R]]]] a, a'-[imino--bis (metileno)] bis[6-fluoro- croman-2---metanol] y [2R[2S[S[S]]]] a,a'-[imino-bis (metileno)] bis[6-fluoro-croman-2-metanol], con las siguientes formulas FJ''OF F'3'GF Nebivolol (SRRR + RSSS)caracterizado porque comprende las siguientes fases: a. se pone a reaccionar una mezcla de cuatro isomeros SR, RS, PR e SS del epoxido de formula (1)(SR+RS+ RR+SS) con una amina R-NH2 donde: - R es un grupo protector seleccionado entre metil, alil, tbutil, bencil, difenilmetil, trifenilmet.il, fluorenil, 9,10- dihidroantracen-9-il, dibencil, donde los anillos aromáticos presentes en los grupos pueden ser eventualmente mono o di sustituidos con un grupo seleccionado entre: halogeno, nitro, una cadena alquílica Cl-C4, CF3, CHF2, un grupo 0R2, donde R2 es un hidrogeno, un alquilo Cl-C4, en un solvente conveniente representado por un alcohol estéricamente obstruido seleccionado entre iPrOH (isopropanol), sec-BuOH, tert-BuOH, isoamílico, 2-metil-2-butanol, 2-metil--2-pentanol, solo o en mezcla con un solvente apolar seleccionado dentro del grupo éter de petroleo, pentano, hexano, ciclohexano, metilciclohexano, heptano, benceno, tolueno, para obtener una mezcla de los cuatro compuestos 2, 3, 4 y 5, donde el par 2/3 está separado del par 4/5; figuras 2, 3, 4 y 5 b. se ponen a reaccionar las aminas 2 y 3, mezcladas, con el par de epoxidos 4 y 5, mezclados, para obtener una mezcla de cuatro compuestos (6, 7, 8 y 9) figuras 6, 7 8 y 9 c. se separan los compuestos 6 y 8 (RSSS + SRRR), mezclados, de 7 y 9 por cristalizacion fraccionada de un primer solvente seleccionado entre etanol, isopropanol, butanol, tert-butanol, 2-metil--2-butanol, y sucesivamente de una mezcla de un solvente polar aprotico seleccionado entre metil acetato, etil acetato, isopropil acetato, acetona, metil etil cetona, acetonitrilo, isopropil éter, con un solvente apolar seleccionado entre pentano, hexano, ciclohexano, metilciclohexano, heptano, benceno, tolueno. d. se elimina el grupo protector R, y opcionalmente se forma sucesivamente la sal hidrocloruro, para obtener el producto final Nebivolol o Nebivolol hidrocloruro.
ARP110100405A 2010-02-11 2011-02-09 Procedimiento para la preparacion del nevibolol AR080149A1 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
ITRM2010A000053A IT1397962B1 (it) 2010-02-11 2010-02-11 Processo per la preparazione del nebivololo.

Publications (1)

Publication Number Publication Date
AR080149A1 true AR080149A1 (es) 2012-03-14

Family

ID=42289104

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP110100405A AR080149A1 (es) 2010-02-11 2011-02-09 Procedimiento para la preparacion del nevibolol

Country Status (21)

Country Link
US (1) US8487122B2 (es)
EP (1) EP2534142B1 (es)
JP (1) JP5698266B2 (es)
KR (1) KR101726468B1 (es)
CN (1) CN102858759B (es)
AR (1) AR080149A1 (es)
AU (1) AU2011214396B2 (es)
BR (1) BR112012020252B8 (es)
CA (1) CA2786833C (es)
EA (1) EA019691B1 (es)
ES (1) ES2445543T3 (es)
HR (1) HRP20140155T1 (es)
IL (1) IL220846A (es)
IT (1) IT1397962B1 (es)
MX (1) MX2012009386A (es)
PL (1) PL2534142T3 (es)
PT (1) PT2534142E (es)
RS (1) RS53134B (es)
SG (1) SG183266A1 (es)
WO (1) WO2011098474A1 (es)
ZA (1) ZA201206221B (es)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8785664B2 (en) * 2010-02-11 2014-07-22 Menarini International Operations Luxembourg S.A. Process for the preparation of nebivolol
ITRM20110418A1 (it) 2011-08-02 2013-02-03 Menarini Int Operations Lu Sa Processo per la preparazione di epossidi quali intermedi per la sintesi del nebivololo.
CN104650022B (zh) * 2013-11-20 2018-09-25 浙江奥翔药业股份有限公司 奈必洛尔的合成方法及其中间体化合物
MX354930B (es) * 2014-10-23 2018-03-20 Consorcio Comex S A De C V Composicion para aerosol usada para marcar o delimitar en cualquier tipo de superficie con una duracion temporal.
JP6921913B2 (ja) * 2015-05-19 2021-08-18 チョーチアン オウスン ファーマシューティカル カンパニー リミテッド ネビボロールの合成方法及びその中間化合物
WO2016183809A1 (zh) * 2015-05-19 2016-11-24 浙江奥翔药业股份有限公司 奈必洛尔的合成方法及其中间体化合物
CN105085499B (zh) * 2015-08-07 2018-09-25 上海现代制药海门有限公司 盐酸奈必洛尔中间体混合物的结晶分离方法
ITUB20160227A1 (it) * 2016-01-21 2017-07-21 Menarini Int Operations Luxembourg Sa Processo per la sintesi di intermedi di Nebivololo

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FR2475298A1 (fr) * 1980-02-01 1981-08-07 Thomson Csf Cellule photovoltaique et pile solaire utilisant une telle cellule
US4654362A (en) * 1983-12-05 1987-03-31 Janssen Pharmaceutica, N.V. Derivatives of 2,2'-iminobisethanol
CA1337429C (en) 1983-12-05 1995-10-24 Guy Rosalia Eugene Van Lommen Derivatives of 2,2'-iminobisethanol
CA1337432C (en) * 1988-03-23 1995-10-24 Raymond M. Xhonneux Method of lowering the blood pressure
US6545040B1 (en) 1988-03-23 2003-04-08 Janssen Pharmaceutica N.V. Method of lowering the blood pressure
DE3809857A1 (de) 1988-03-24 1989-10-05 Philips Patentverwaltung Blasformmaschine zum blasformen von hohlkoerpern mit polsterregelung
TW355683B (en) 1994-02-17 1999-04-11 Janssen Pharmaceutica Nv Composition containing micronized nebivolol
HU227236B1 (en) * 2002-11-06 2010-12-28 Egis Gyogyszergyar Nyilvanosan Muekoedoe Reszvenytarsasag New process for the production of racemic and the pure [2s[2r*[r[r*]]]]-and [2r[2s*[s[s*]]]]-enantiomers of nebivolol
US8604222B2 (en) 2004-07-30 2013-12-10 Forest Laboratories Holdings Limited Nebivolol and its pharmaceutically acceptable salts, process for preparation and pharmaceutical compositions of nebivolol
KR20070046877A (ko) 2004-08-13 2007-05-03 하두르 메카니즘 프로덕션 엘티디 다중 트랙 프로파일 랩핑기용 시스템 및 방법
AT502220A1 (de) * 2005-07-19 2007-02-15 Pharmacon Forschung & Beratung Verfahren zur herstellung von nebivolol
WO2007041805A1 (en) 2005-10-13 2007-04-19 Burns Bay Investments Pty Ltd Elongate lighting means
EP1803716B1 (en) 2005-12-28 2012-07-25 Acino Pharma AG A process for preparation of racemic nebivolol
US7560575B2 (en) * 2005-12-28 2009-07-14 Acino Pharma Ag Process for preparation of racemic Nebivolol
WO2007083318A1 (en) 2006-01-18 2007-07-26 Hetero Drugs Limited Process for isolation of desired isomers of nebivolol intermediates
CN101541791B (zh) 2006-11-27 2014-01-29 Zach系统股份公司 制备奈必洛尔的方法
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Also Published As

Publication number Publication date
PL2534142T3 (pl) 2014-05-30
HK1179626A1 (en) 2013-10-04
EA019691B1 (ru) 2014-05-30
EP2534142A1 (en) 2012-12-19
ZA201206221B (en) 2014-01-29
US20120316351A1 (en) 2012-12-13
HRP20140155T1 (hr) 2014-03-14
US8487122B2 (en) 2013-07-16
CN102858759A (zh) 2013-01-02
BR112012020252A2 (pt) 2016-08-09
SG183266A1 (en) 2012-09-27
AU2011214396A1 (en) 2012-10-04
CA2786833A1 (en) 2011-08-18
AU2011214396B2 (en) 2014-06-05
KR101726468B1 (ko) 2017-04-12
WO2011098474A1 (en) 2011-08-18
ITRM20100053A1 (it) 2011-08-12
BR112012020252B1 (pt) 2021-05-04
BR112012020252B8 (pt) 2021-05-25
IL220846A0 (en) 2012-08-30
KR20120129952A (ko) 2012-11-28
RS53134B (sr) 2014-06-30
EA201201127A1 (ru) 2013-01-30
MX2012009386A (es) 2012-09-12
JP5698266B2 (ja) 2015-04-08
IL220846A (en) 2014-12-31
ES2445543T3 (es) 2014-03-03
PT2534142E (pt) 2014-02-24
IT1397962B1 (it) 2013-02-04
CN102858759B (zh) 2015-12-16
JP2013519647A (ja) 2013-05-30
EP2534142B1 (en) 2013-11-27
CA2786833C (en) 2017-03-07

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