AR084037A1 - Proceso para la preparacion del nebivolol - Google Patents
Proceso para la preparacion del nebivololInfo
- Publication number
- AR084037A1 AR084037A1 ARP110104443A ARP110104443A AR084037A1 AR 084037 A1 AR084037 A1 AR 084037A1 AR P110104443 A ARP110104443 A AR P110104443A AR P110104443 A ARP110104443 A AR P110104443A AR 084037 A1 AR084037 A1 AR 084037A1
- Authority
- AR
- Argentina
- Prior art keywords
- formula
- nebivolol
- mixture
- ester
- acid
- Prior art date
Links
- 229960000619 nebivolol Drugs 0.000 title abstract 3
- KOHIRBRYDXPAMZ-YHBROIRLSA-N (S,R,R,R)-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-YHBROIRLSA-N 0.000 title abstract 2
- 238000000034 method Methods 0.000 title abstract 2
- 239000000203 mixture Substances 0.000 abstract 7
- 239000004593 Epoxy Substances 0.000 abstract 4
- 239000002253 acid Substances 0.000 abstract 4
- 150000002148 esters Chemical class 0.000 abstract 4
- 230000015572 biosynthetic process Effects 0.000 abstract 3
- 238000003786 synthesis reaction Methods 0.000 abstract 3
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 abstract 2
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 abstract 1
- 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 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract 1
- 125000000217 alkyl group Chemical group 0.000 abstract 1
- 150000001414 amino alcohols Chemical class 0.000 abstract 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 abstract 1
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 abstract 1
- 150000002118 epoxides Chemical class 0.000 abstract 1
- 230000000707 stereoselective effect Effects 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic 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
- C07D407/02—Heterocyclic 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
- C07D407/12—Heterocyclic 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
-
- 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
-
- 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
- C12P17/16—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms containing two or more hetero rings
- C12P17/162—Heterorings having oxygen atoms as the only ring heteroatoms, e.g. Lasalocid
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Health & Medical Sciences (AREA)
- General Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Microbiology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyrane Compounds (AREA)
- Steroid Compounds (AREA)
Abstract
Reivindicación 1: Un proceso de síntesis de d-nebivolol y/o l-nebivolol con las formulas (12) y (13) que comprende los siguientes pasos: a) se hidroliza la mezcla de enantiómeros del éster del ácido 6-fluoro-2-carboxílico de fórmula (1), en la que R1 es un grupo alquilo C1-5 lineal o ramificado, para dar una mezcla de ácido de fórmula (2) y de éster de fórmula (3); b) se utilizan respectivamente el ácido de fórmula (2) obtenido de esta manera por síntesis de la mezcla de epóxidos de fórmula (4) y el éster de fórmula (3) así obtenido por la síntesis de las mezclas de epóxidos de fórmula (5); c) se separan las mezclas de epóxidos de fórmula (4) y (5) para obtener respectivamente los compuestos de fórmula (6) + (7) y (8) + (9); d) se hacen reaccionar los aminoalcoholes de fórmula (6) y (8) con los epóxidos de fórmula (7) y (9) para obtener l-bencil nebivolol de fórmula (10) y el d-bencil nebivolol de fórmula (11); e) se separa el grupo protector bencil, caracterizado porque, en el paso (a), se hidroliza mediante una reacción de hidrólisis enzimática estereoselectiva, para dar la mezcla del ácido de fórmula (2) con un exceso enantiomérico > 70% y del éster S de fórmula (3) con un exceso enantiomérico > 70%; y que en el paso (c) se separan las mezclas de epóxidos de fórmula (4) y (5) cinéticamente, poniéndolo a reaccionar con bencilamina en un alcohol estéricamente impedido.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ITRM2010A000622A IT1402974B1 (it) | 2010-11-30 | 2010-11-30 | Processo per la preparazione del nebivololo. |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AR084037A1 true AR084037A1 (es) | 2013-04-17 |
Family
ID=43743017
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP110104443A AR084037A1 (es) | 2010-11-30 | 2011-11-30 | Proceso para la preparacion del nebivolol |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US9090922B2 (es) |
| EP (1) | EP2646426B1 (es) |
| JP (1) | JP5973459B2 (es) |
| KR (1) | KR101797799B1 (es) |
| CN (1) | CN103228640B (es) |
| AR (1) | AR084037A1 (es) |
| AU (1) | AU2011355143B2 (es) |
| BR (1) | BR112013013224B1 (es) |
| CA (1) | CA2818465C (es) |
| CY (1) | CY1117233T1 (es) |
| DK (1) | DK2646426T3 (es) |
| EA (1) | EA022194B1 (es) |
| ES (1) | ES2553266T3 (es) |
| HR (1) | HRP20151432T1 (es) |
| HU (1) | HUE026722T2 (es) |
| IL (1) | IL226153A (es) |
| IT (1) | IT1402974B1 (es) |
| MX (1) | MX2013005930A (es) |
| PL (1) | PL2646426T3 (es) |
| PT (1) | PT2646426E (es) |
| RS (1) | RS54463B1 (es) |
| SG (1) | SG190132A1 (es) |
| SI (1) | SI2646426T1 (es) |
| SM (1) | SMT201600006B (es) |
| WO (1) | WO2012095707A1 (es) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| 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 |
| ITUB20160227A1 (it) * | 2016-01-21 | 2017-07-21 | Menarini Int Operations Luxembourg Sa | Processo per la sintesi di intermedi di Nebivololo |
| CN107686480A (zh) * | 2016-08-04 | 2018-02-13 | 上海朴颐化学科技有限公司 | 一种制备奈比洛尔环氧化物单一异构体的方法 |
| 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 |
| CN110791488A (zh) * | 2019-12-05 | 2020-02-14 | 西南交通大学 | 用于拆分手性化合物的脂肪酶及其制备方法和应用 |
| CN114150036B (zh) * | 2021-12-23 | 2024-01-09 | 华东理工大学 | 一种用于制备光学纯的6-氟-色满-2-羧酸的连续双相分批拆分工艺 |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| US5037747A (en) | 1988-01-26 | 1991-08-06 | Hoffmann-La Roche Inc. | Production of benzopyran-2-carboxylic acids and esters by enzymatic hydrolysis |
| CA1337432C (en) | 1988-03-23 | 1995-10-24 | Raymond M. Xhonneux | Method of lowering the blood pressure |
| US5089637A (en) | 1990-03-21 | 1992-02-18 | Pfizer Inc. | Process and intermediates for 2r-benzyl-chroman-6-carbaldehyde |
| US5912164A (en) * | 1993-03-03 | 1999-06-15 | Laboratorios Menarini S.A. | Stereoselective hydrolysis of chiral carboxylic acid esters using esterase from ophiostoma or ceratocystis |
| GB9304256D0 (en) | 1993-03-03 | 1993-04-21 | Chiros Ltd | Arylalkanoic acid resolution |
| GB9304351D0 (en) | 1993-03-03 | 1993-04-21 | Chiros Ltd | Arylalkanoic acid resolution and microorganisms for use therein |
| DE4430089A1 (de) | 1994-08-25 | 1996-02-29 | Bayer Ag | Verfahren zur enzymatischen Herstellung von enantiomerenreinen Chroman-2-carbonsäuren und deren Derivaten |
| US5658796A (en) | 1995-06-07 | 1997-08-19 | Seprachem, Inc. | Optical resolution of alkyl chroman-2-carboxylates |
| KR100896266B1 (ko) * | 2004-07-30 | 2009-05-08 | 토렌트 파마슈티칼스 리미티드 | 네비볼올 및 그의 약학적으로 허용되는 염, 네비볼올의제조방법 및 네비볼올의 약학적 조성물 |
| EP1626093A1 (en) | 2004-08-11 | 2006-02-15 | Dow Global Technologies Inc. | Process for the production of (S)-5-chloro-2-isopropylpent-4-enoic acid esters |
| US20070021623A1 (en) | 2004-08-11 | 2007-01-25 | Hetero Drugs Limited | Novel process for preparation of nebivolol intermediates |
| 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 |
| EP1973895A1 (en) | 2006-01-18 | 2008-10-01 | 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 |
| DE602007007666D1 (de) | 2006-11-27 | 2010-08-19 | Zach System Spa | Verfahren zur herstellung von nebivolol |
-
2010
- 2010-11-30 IT ITRM2010A000622A patent/IT1402974B1/it active
-
2011
- 2011-11-30 DK DK11815574.6T patent/DK2646426T3/en active
- 2011-11-30 AU AU2011355143A patent/AU2011355143B2/en active Active
- 2011-11-30 HR HRP20151432TT patent/HRP20151432T1/hr unknown
- 2011-11-30 PT PT118155746T patent/PT2646426E/pt unknown
- 2011-11-30 EA EA201300646A patent/EA022194B1/ru unknown
- 2011-11-30 AR ARP110104443A patent/AR084037A1/es active IP Right Grant
- 2011-11-30 KR KR1020137016907A patent/KR101797799B1/ko active Active
- 2011-11-30 EP EP11815574.6A patent/EP2646426B1/en active Active
- 2011-11-30 CN CN201180056422.5A patent/CN103228640B/zh active Active
- 2011-11-30 PL PL11815574T patent/PL2646426T3/pl unknown
- 2011-11-30 ES ES11815574.6T patent/ES2553266T3/es active Active
- 2011-11-30 HU HUE11815574A patent/HUE026722T2/en unknown
- 2011-11-30 US US13/990,220 patent/US9090922B2/en active Active
- 2011-11-30 WO PCT/IB2011/055385 patent/WO2012095707A1/en not_active Ceased
- 2011-11-30 BR BR112013013224-8A patent/BR112013013224B1/pt active IP Right Grant
- 2011-11-30 SI SI201130691T patent/SI2646426T1/sl unknown
- 2011-11-30 MX MX2013005930A patent/MX2013005930A/es active IP Right Grant
- 2011-11-30 RS RS20150853A patent/RS54463B1/sr unknown
- 2011-11-30 JP JP2013541461A patent/JP5973459B2/ja active Active
- 2011-11-30 CA CA2818465A patent/CA2818465C/en active Active
- 2011-11-30 SG SG2013034095A patent/SG190132A1/en unknown
-
2013
- 2013-05-05 IL IL226153A patent/IL226153A/en active IP Right Grant
-
2015
- 2015-12-22 CY CY20151101175T patent/CY1117233T1/el unknown
-
2016
- 2016-01-07 SM SM201600006T patent/SMT201600006B/it unknown
Also Published As
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Legal Events
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| FG | Grant, registration |