HRP20140922T1 - Postupak dobivanja nebivolola - Google Patents
Postupak dobivanja nebivolola Download PDFInfo
- Publication number
- HRP20140922T1 HRP20140922T1 HRP20140922AT HRP20140922T HRP20140922T1 HR P20140922 T1 HRP20140922 T1 HR P20140922T1 HR P20140922A T HRP20140922A T HR P20140922AT HR P20140922 T HRP20140922 T HR P20140922T HR P20140922 T1 HRP20140922 T1 HR P20140922T1
- Authority
- HR
- Croatia
- Prior art keywords
- formula
- compound
- halogenmethyllithium
- derivative
- image
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims 20
- 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 claims 3
- 229960000619 nebivolol Drugs 0.000 title claims 3
- 150000001875 compounds Chemical class 0.000 claims 18
- 238000006243 chemical reaction Methods 0.000 claims 7
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims 4
- 239000003153 chemical reaction reagent Substances 0.000 claims 3
- 125000005843 halogen group Chemical group 0.000 claims 3
- 125000001979 organolithium group Chemical group 0.000 claims 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical group [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims 2
- JPOXNPPZZKNXOV-UHFFFAOYSA-N bromochloromethane Chemical group ClCBr JPOXNPPZZKNXOV-UHFFFAOYSA-N 0.000 claims 2
- 239000011541 reaction mixture Substances 0.000 claims 2
- 239000002904 solvent Substances 0.000 claims 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims 2
- 239000004593 Epoxy Substances 0.000 claims 1
- VQEVKEKJZVEGPH-UHFFFAOYSA-N lithium;chloromethane Chemical group [Li+].Cl[CH2-] VQEVKEKJZVEGPH-UHFFFAOYSA-N 0.000 claims 1
- 238000007363 ring formation reaction Methods 0.000 claims 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- 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
- C07D311/66—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
-
- 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
- C07D407/04—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 directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrane Compounds (AREA)
- Saccharide Compounds (AREA)
- Steroid Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Claims (16)
1. Postupak dobivanja spoja formule
[image]
,
gdje je X atom halogena,
naznačen time što se sastoji u reakciji spoja formule
[image]
,
gdje je R (C1-C6)-alkilna skupina,
s derivatom halogenmetillitija formule Li-CH2-X, u kojoj je X definiran kao gore.
2. Postupak u skladu s patentnim zahtjevom 1, naznačen time što se derivat halogenmetillitija dobiva u reakcijskom sustavu.
3. Postupak u skladu s patentnim zahtjevom 2, naznačen time što se derivat halogenmetillitija dobiva dodavanjem organolitijskog reagensa dihalogenmetanu.
4. Postupak u skladu s patentnim zahtjevom 3, naznačen time što je dihalogenmetan bromklormetan.
5. Postupak u skladu s patentnim zahtjevom 3 ili zahtjevom 4, naznačen time što je organolitijski reagens n-butillitij.
6. Postupak u skladu s bilo kojim od patentnih zahtjeva 3 do 5, naznačen time što se spoj formule (VI), dihalogenmetan i organolitijski reagens upotrebljava u molarnom omjeru od otprilike 1:2:2.
7. Postupak u skladu s bilo kojim od prethodnih zahtjeva, naznačen time što je derivat halogenmetillitija klormetillitij.
8. Postupak u skladu s bilo kojim od prethodnih zahtjeva, naznačen time što se reakciju spoja formule VI s derivatom halogenmetillitija provodi u prisutnosti otapala.
9. Postupak u skladu s patentnim zahtjevom 8, naznačen time što je otapalo tetrahidrofuran (THF).
10. Postupak u skladu s patentnim zahtjevom 1, naznačen time što se dodavanje halogenmetillitija spoju formule (VI) provodi u rasponu temperatura od –100 °C do 0 °C.
11. Postupak u skladu s patentnim zahtjevom 10, naznačen time što se dodavanje halogenmetillitija provodi u rasponu temperatura od –85 °C do –50 °C.
12. Postupak dobivanja spoja formule
[image]
,
naznačen time što se sastoji u prevođenju spoja formule (VI) u spoj formule (I) postupkom u skladu s patentnim zahtjevom 1.
13. Postupak u skladu s patentnim zahtjevom 12, naznačen time što se dodatno sastoji u
reduciranju spoja formule I kako bi se dobilo spoj formule (VIII):
[image]
,
u kojoj je X atom halogena, i
reakciji navedenog spoja formule (VIII) s bazom kako bi se dobilo epoksidni spoj formule (VII).
14. Postupak dobivanja spoja formule
[image]
,
naznačen time što se sastoji u reakciji spoja formule
[image]
,
u kojoj je R (C1-C6)-alkilna skupina, s derivatom halogenmetillitija formule Li-CH2-X, u kojoj je X atom halogena, kako bi se dobilo reakcijsku smjesu;
reduciranju navedene reakcijske smjese na licu mjesta; i
cikliziranju u prisutnosti baze.
15. Postupak dobivanja nebivolola, naznačen time što se sastoji u prevođenju spoja formule (VI) u spoj formule (I) postupkom u skladu s patentnim zahtjevom 1.
16. Postupak dobivanja nebivolola, naznačen time što se sastoji u prevođenju u jednoj posudi spoja formule (VI) u spoj formule (VII) postupkom u skladu s patentnim zahtjevom 14.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0856415 | 2008-09-24 | ||
| PCT/FR2009/051775 WO2010034927A1 (fr) | 2008-09-24 | 2009-09-22 | Procede de preparation de nebivolol |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20140922T1 true HRP20140922T1 (hr) | 2014-11-07 |
Family
ID=40527387
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20140922AT HRP20140922T1 (hr) | 2008-09-24 | 2014-09-26 | Postupak dobivanja nebivolola |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US8981127B2 (hr) |
| EP (1) | EP2328883B1 (hr) |
| JP (1) | JP5744738B2 (hr) |
| CN (1) | CN102164906A (hr) |
| AU (1) | AU2009295730B2 (hr) |
| BR (1) | BRPI0919257B8 (hr) |
| CA (1) | CA2736600C (hr) |
| ES (1) | ES2523343T3 (hr) |
| HR (1) | HRP20140922T1 (hr) |
| IL (1) | IL211410A (hr) |
| PL (1) | PL2328883T3 (hr) |
| WO (1) | WO2010034927A1 (hr) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102180855B (zh) * | 2011-03-01 | 2015-11-25 | 浙江华海药业股份有限公司 | 一种奈必洛尔中间体的提纯方法 |
| 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. |
| PT2907809T (pt) | 2014-02-14 | 2019-01-16 | Corden Pharma Int Gmbh | Processo sem base para a preparação de intermediários de cetona utilizáveis para fabrico de nebivolol |
| 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 |
| ITUB20160227A1 (it) * | 2016-01-21 | 2017-07-21 | Menarini Int Operations Luxembourg Sa | Processo per la sintesi di intermedi di Nebivololo |
| CN108997297B (zh) * | 2018-07-17 | 2020-12-01 | 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、用于制备该奈必洛尔中间体的中间体及其制备方法 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5591885A (en) | 1994-09-23 | 1997-01-07 | Hoffman-La Roche Inc. | Process for the preparation of halogenated α-aminoketone compounds |
| US5523463A (en) * | 1994-09-23 | 1996-06-04 | Hoffmann-La Roche Inc. | Method of producing halogenated and alpha-aminoalchohols |
| US6127556A (en) * | 1996-12-31 | 2000-10-03 | G. D. Searle & Co. | Epoxide formation by continuous in-situ synthesis process |
| EP1534683A4 (en) * | 2002-06-27 | 2005-08-24 | Nitromed Inc | CYCLOOXYGENASE-2 SELECTIVE INHIBITORS, COMPOSITIONS AND METHOD OF USE |
| EP1937649A1 (en) * | 2005-10-14 | 2008-07-02 | Neurosearch A/S | Imidazole derivatives for the treatment of anxiety and related diseases |
| US7560575B2 (en) * | 2005-12-28 | 2009-07-14 | Acino Pharma Ag | Process for preparation of racemic Nebivolol |
| ITMI20061889A1 (it) * | 2006-10-03 | 2008-04-04 | Zambon Spa | Processo di preparazione di nebivololo |
| EP2061759B1 (en) * | 2006-10-04 | 2013-03-27 | Bristol-Myers Squibb Company | Cyclic modulators of chemokine receptor activity |
| NZ582249A (en) * | 2007-06-28 | 2012-06-29 | Intervet Int Bv | Substituted piperazines as cb1 antagonists |
-
2009
- 2009-09-22 CA CA2736600A patent/CA2736600C/fr active Active
- 2009-09-22 CN CN2009801373139A patent/CN102164906A/zh active Pending
- 2009-09-22 WO PCT/FR2009/051775 patent/WO2010034927A1/fr active Application Filing
- 2009-09-22 JP JP2011528395A patent/JP5744738B2/ja active Active
- 2009-09-22 US US13/120,690 patent/US8981127B2/en active Active
- 2009-09-22 BR BRPI0919257A patent/BRPI0919257B8/pt active IP Right Grant
- 2009-09-22 ES ES09747893.7T patent/ES2523343T3/es active Active
- 2009-09-22 PL PL09747893T patent/PL2328883T3/pl unknown
- 2009-09-22 EP EP09747893.7A patent/EP2328883B1/fr active Active
- 2009-09-22 AU AU2009295730A patent/AU2009295730B2/en active Active
-
2011
- 2011-02-24 IL IL211410A patent/IL211410A/en active IP Right Grant
-
2014
- 2014-09-26 HR HRP20140922AT patent/HRP20140922T1/hr unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AU2009295730A1 (en) | 2010-04-01 |
| WO2010034927A1 (fr) | 2010-04-01 |
| EP2328883B1 (fr) | 2014-08-06 |
| AU2009295730B2 (en) | 2013-12-19 |
| PL2328883T3 (pl) | 2015-01-30 |
| CN102164906A (zh) | 2011-08-24 |
| BRPI0919257A2 (pt) | 2015-08-18 |
| EP2328883A1 (fr) | 2011-06-08 |
| IL211410A (en) | 2015-10-29 |
| BRPI0919257B1 (pt) | 2021-05-04 |
| CA2736600C (fr) | 2017-03-21 |
| IL211410A0 (en) | 2011-05-31 |
| US8981127B2 (en) | 2015-03-17 |
| CA2736600A1 (fr) | 2010-04-01 |
| JP5744738B2 (ja) | 2015-07-08 |
| BRPI0919257B8 (pt) | 2021-05-25 |
| JP2012503636A (ja) | 2012-02-09 |
| ES2523343T3 (es) | 2014-11-25 |
| US20110237808A1 (en) | 2011-09-29 |
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