AR079932A1 - Metodo para la preparacion de nebivolol y compuestos intermediarios. - Google Patents
Metodo para la preparacion de nebivolol y compuestos intermediarios.Info
- Publication number
- AR079932A1 AR079932A1 ARP110100167A ARP110100167A AR079932A1 AR 079932 A1 AR079932 A1 AR 079932A1 AR P110100167 A ARP110100167 A AR P110100167A AR P110100167 A ARP110100167 A AR P110100167A AR 079932 A1 AR079932 A1 AR 079932A1
- Authority
- AR
- Argentina
- Prior art keywords
- formula
- nebivolol
- precursors
- group
- enantiomerically pure
- Prior art date
Links
- KOHIRBRYDXPAMZ-YHBROIRLSA-N (S,R,R,R)-nebivolol Chemical class C1CC2=CC(F)=CC=C2O[C@H]1[C@H](O)CNC[C@@H](O)[C@H]1OC2=CC=C(F)C=C2CC1 KOHIRBRYDXPAMZ-YHBROIRLSA-N 0.000 title abstract 7
- 150000001875 compounds Chemical class 0.000 title abstract 4
- 229960000619 nebivolol Drugs 0.000 title abstract 4
- 238000000034 method Methods 0.000 title abstract 2
- 239000002243 precursor Substances 0.000 abstract 10
- 239000000543 intermediate Substances 0.000 abstract 4
- 150000002576 ketones Chemical class 0.000 abstract 4
- KOHIRBRYDXPAMZ-YHDSQAASSA-N (R,S,S,S)-nebivolol Chemical compound C1CC2=CC(F)=CC=C2O[C@H]1[C@@H](O)CNC[C@H](O)[C@H]1OC2=CC=C(F)C=C2CC1 KOHIRBRYDXPAMZ-YHDSQAASSA-N 0.000 abstract 3
- 230000008878 coupling Effects 0.000 abstract 3
- 238000010168 coupling process Methods 0.000 abstract 3
- 238000005859 coupling reaction Methods 0.000 abstract 3
- 125000002252 acyl group Chemical group 0.000 abstract 2
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 abstract 2
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 abstract 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 2
- 150000001412 amines Chemical class 0.000 abstract 1
- 125000004429 atom Chemical group 0.000 abstract 1
- 230000015572 biosynthetic process Effects 0.000 abstract 1
- 229910052736 halogen Inorganic materials 0.000 abstract 1
- 125000005843 halogen group Chemical group 0.000 abstract 1
- 150000002367 halogens Chemical class 0.000 abstract 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 1
- 125000006239 protecting group Chemical group 0.000 abstract 1
- 238000003786 synthesis reaction Methods 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic 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
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
-
- 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
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/02—Oxygen as only ring hetero atoms
- C12P17/06—Oxygen as only ring hetero atoms containing a six-membered hetero ring, e.g. fluorescein
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Health & Medical Sciences (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Reivindicacion 1: Procedimiento para la síntesis de nebivolol racémico de la formula (1) a partir de compuestos enantioméricamente puros de la formula (4a) y (4b) en donde se obtiene nebivolol racémico por mezcla de los compuestos enantioméricamente puros d-nebivolol (1a) y l-nebivolol (1b), se sintetizan los compuestos d-nebivolol (1a) y I-nebivolol (1b), de modo independiente entre sí, como compuestos enantioméricamente puros preparando (1a) y (1b) por acoplamientos individuales de 4 intermediarios enantioméricamente puros de la formula (2a-d) con los correspondientes precursores de la formula (3a-d), en donde por acoplamiento de (2a) con (3b) o (2b) con (3a) se obtiene d-nebivolol (1a) y por acoplamiento de (2c) con (3d) o (2d) con (3c) se obtiene l-nebivolol (1b) y en donde PG en los intermediarios de la formula (2a-d) significa un átomo de hidrogeno o un grupo protector de amina y X significa en los precursores de la formula (3a-d) un átomo de halogeno, un grupo hidroxilo, un grupo acilo, un grupo alquilsulfoniloxi o un grupo arilsulfoniloxi, los intermediarios de la formula (2a-d) se forman de manera individual a partir de los correspondientes precursores directos de la formula (3a-d), en donde el intermediario (2a) se forma a partir de (3a), el intermediario (2b) se forma a partir de (3b), el intermediario (2c) se forma a partir de (3c) y el intermediario (2d) se forma a partir de (3d), los precursores de la formula (3a-d) se forman específicamente por reduccion de los precursores de cetona enantioméricamente puros de la formula (4a,b), en donde los precursores de la formula (3a) y (3d) provienen del precursor de cetona de la formula (4a), y los precursores de la formula (3b) y (3c) provienen del precursor de cetona de la formula (4b) y Z en los precursores de cetona (4a,b) significa un átomo de halogeno, una funcion hidroxilo, un grupo acilo, un grupo alquilsulfoniloxi o un grupo arilsulfoniloxi.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102010005953A DE102010005953A1 (de) | 2010-01-27 | 2010-01-27 | Verfahren zur Herstellung von Nebivolol |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AR079932A1 true AR079932A1 (es) | 2012-02-29 |
Family
ID=43617918
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP110100167A AR079932A1 (es) | 2010-01-27 | 2011-01-19 | Metodo para la preparacion de nebivolol y compuestos intermediarios. |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US20130005001A1 (es) |
| EP (1) | EP2528905B1 (es) |
| AR (1) | AR079932A1 (es) |
| DE (1) | DE102010005953A1 (es) |
| WO (1) | WO2011091968A1 (es) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2907810A1 (en) | 2014-02-14 | 2015-08-19 | Corden Pharma International GmbH | A new method for producing nebivolol hydrochloride of high purity |
| EP2907809B1 (en) | 2014-02-14 | 2018-08-22 | Corden Pharma International GmbH | Base-free process for the preparation of ketone intermediates usable for manufacture of nebivolol |
| DE102014107132A1 (de) | 2014-05-20 | 2015-11-26 | Corden Pharma International Gmbh | Verfahren zur Herstellung von Epoxiden die in der Herstellung von Nebivolol und dessen Derivaten einsetzbar sind |
| CN104610215A (zh) * | 2015-01-19 | 2015-05-13 | 浙江海翔药业股份有限公司 | 一种奈必洛尔中间体的制备方法及奈必洛尔的制备方法 |
| CN105503842A (zh) * | 2015-12-24 | 2016-04-20 | 广安凯特医药化工有限公司 | 盐酸奈必洛尔环氧中间体6-氟-2-环氧乙基色满的制备方法 |
| ITUB20160227A1 (it) | 2016-01-21 | 2017-07-21 | Menarini Int Operations Luxembourg Sa | Processo per la sintesi di intermedi di Nebivololo |
| CN108300743B (zh) * | 2018-02-06 | 2021-05-14 | 江苏八巨药业有限公司 | 一种(r)-2-氯-1-(6-氟-苯并二氢吡喃-2-基)-1-乙醇的生物催化方法 |
| CN108314670B (zh) * | 2018-02-06 | 2020-04-07 | 江苏八巨药业有限公司 | 一种(s)-2-氯-1-(6-氟-1-苯并二氢吡喃-2-基)-乙醇的制备方法 |
| CN108913729A (zh) * | 2018-06-26 | 2018-11-30 | 浙江车头制药股份有限公司 | 一种奈必洛尔中间体的酶还原制备方法 |
| CN110218718A (zh) * | 2019-06-19 | 2019-09-10 | 南京趣酶生物科技有限公司 | 固定化酮还原酶突变体及其在制备奈必洛尔手性醇中间体及其类似物中的应用 |
| CN110373420A (zh) * | 2019-06-19 | 2019-10-25 | 南京趣酶生物科技有限公司 | 一种新酶菌株和酶催化剂的制备方法和应用 |
| CN117567422A (zh) * | 2023-11-24 | 2024-02-20 | 江苏威奇达药业有限公司 | 一种连续流反应合成盐酸奈必洛尔的方法 |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1337429C (en) | 1983-12-05 | 1995-10-24 | Guy Rosalia Eugene Van Lommen | Derivatives of 2,2'-iminobisethanol |
| US4654362A (en) | 1983-12-05 | 1987-03-31 | Janssen Pharmaceutica, N.V. | 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 |
| 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 |
| DE102004022686A1 (de) * | 2004-05-05 | 2005-11-24 | Basf Ag | Verfahren zur Herstellung optisch aktiver Alkohole |
| KR100896266B1 (ko) | 2004-07-30 | 2009-05-08 | 토렌트 파마슈티칼스 리미티드 | 네비볼올 및 그의 약학적으로 허용되는 염, 네비볼올의제조방법 및 네비볼올의 약학적 조성물 |
| US20070021623A1 (en) | 2004-08-11 | 2007-01-25 | Hetero Drugs Limited | Novel process for preparation of nebivolol intermediates |
| AT502220A1 (de) | 2005-07-19 | 2007-02-15 | Pharmacon Forschung & Beratung | Verfahren zur herstellung von nebivolol |
| US7560575B2 (en) | 2005-12-28 | 2009-07-14 | Acino Pharma Ag | Process for preparation of racemic Nebivolol |
| EP1803716B1 (en) | 2005-12-28 | 2012-07-25 | Acino Pharma AG | A process for preparation of racemic nebivolol |
| EP1973895A1 (en) | 2006-01-18 | 2008-10-01 | Hetero Drugs Limited | Process for isolation of desired isomers of nebivolol intermediates |
| ITMI20061889A1 (it) | 2006-10-03 | 2008-04-04 | Zambon Spa | Processo di preparazione di nebivololo |
| DE602007007666D1 (de) * | 2006-11-27 | 2010-08-19 | Zach System Spa | Verfahren zur herstellung von nebivolol |
| ITMI20080547A1 (it) | 2008-03-31 | 2009-10-01 | Zach System Spa | Processo di preparazione di nebivololo |
-
2010
- 2010-01-27 DE DE102010005953A patent/DE102010005953A1/de not_active Ceased
-
2011
- 2011-01-19 AR ARP110100167A patent/AR079932A1/es unknown
- 2011-01-21 US US13/574,348 patent/US20130005001A1/en not_active Abandoned
- 2011-01-21 WO PCT/EP2011/000246 patent/WO2011091968A1/de not_active Ceased
- 2011-01-21 EP EP11701454.8A patent/EP2528905B1/de not_active Not-in-force
Also Published As
| Publication number | Publication date |
|---|---|
| EP2528905A1 (de) | 2012-12-05 |
| WO2011091968A1 (de) | 2011-08-04 |
| DE102010005953A1 (de) | 2011-07-28 |
| EP2528905B1 (de) | 2015-10-07 |
| US20130005001A1 (en) | 2013-01-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AR079932A1 (es) | Metodo para la preparacion de nebivolol y compuestos intermediarios. | |
| UY33317A (es) | Nuevos derivados de pirazol | |
| CO6771439A2 (es) | Inhibidores de benzodioxano de la producción de leucotrieno | |
| UA113643C2 (xx) | N-цикліламіди як нематоциди | |
| MX2012005358A (es) | Procedimiento para la preparacion de etexilato de dabigatran. | |
| GT201300078A (es) | Proceso para la preparacion de inhibidores de pan-cdk de la formula ( i ), e intermediarios de la preparacion | |
| MX2020008468A (es) | Mejoramiento de autofagia o incremento de longevidad por administracion de urolitinas o precursores de las mismas. | |
| ECSP11011244A (es) | Nuevos herbicidas. | |
| UY32296A (es) | Nuevos compuestos | |
| UY30292A1 (es) | Derivados de 4-(2-amino-1-hidroxietil)fenol como agonistas del receptor b(beta)2 adrenérgico | |
| MX390726B (es) | Procesos para preparar compuestos de quinolina y composiciones farmaceuticas que contienen tales compuestos. | |
| CU24354B1 (es) | Procedimiento de obtención de derivados de tetrafluoropropilmorfolina | |
| MX344911B (es) | Compuestos de eter amido-piridilico y composiciones y su uso contra parasitos. | |
| CL2011001405A1 (es) | Procedimiento para la preparacion de n-[2-(7-metoxi-1-naftil)etil]acetamida, agometalina. | |
| AR096165A1 (es) | Síntesis de 3-(5-amino-2-metil-4-oxoquinazolin-3(4h)-il)piperidin-2,6-diona | |
| IT1398825B1 (it) | Macchina per la produzione di manufatti ceramici. | |
| ECSP13012914A (es) | Síntesis de derivados de 2-carboxamida-cicloamino-urea | |
| CL2013000589A1 (es) | Metodo para preparar derivados del acido 3-amino-4-(3,4,5,5-tetrasustituido)-2-oxo-piperidin-1-il)-4-butirico por reaccion entre un acido 3,4-diaminobutanoico y un acido 5-hidroxipentanoico. | |
| CL2010001639A1 (es) | Proceso para preparacion del hemitartrato de [5-(4,6-dimetil-1h-benzoimidazol-2-il-metil-pirimidin-2-il]-[3-(metil-piperidin-4-il)propil]amina; proceso de recristalizacion del hemitartrato; y hemitaatrato cristalino de [5-(4,6-dimetil-1h-benzoimidazol-2-il)-4-metil- pirimidin-2-il]-[3-(1-metil-piperidin-4-il)-propil]-amina. | |
| UY32635A (es) | Derivados de bis-(sulfonilamino) en terapia 735 | |
| UY33722A (es) | Oxazolidinonas como moduladores de mglur5 | |
| CL2012002541A1 (es) | Compuesto cristalino hidrato del hidrobromuro de agomelatina; metodo de preparacion del compuesto; composicion farmaceutica; uso del compuesto para tratar trastornos del sueño, estres, ansiedad, depresion mayor, esquizofrenia, entre otros. | |
| AR085291A1 (es) | Metodos para sintetizar derivados del precursor z de molibdopterina | |
| BR112013031334A2 (pt) | método para preparar zeólitos do tipo lta utilizando um agente de dirigir estrutura novo | |
| MX2012001722A (es) | Nuevo procedimiento de sintesis de la ivabradina y de sus sales de adicion a un acido farmaceuticamente aceptable. |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FB | Suspension of granting procedure |