ME00814B - NOVI POSTUPAK SINTEZE 7,8-DIMETOKSI-1 ,3-DIHIDR0-2H-3-BENZAZEPIN-2-ON-a l PRIMENA U SINTEZI IVABRADINA l NJEGOVIH ADICIONIH SOLI SA FARMACEUTSKI PRIHVATLJIVOM KISELINOM - Google Patents
NOVI POSTUPAK SINTEZE 7,8-DIMETOKSI-1 ,3-DIHIDR0-2H-3-BENZAZEPIN-2-ON-a l PRIMENA U SINTEZI IVABRADINA l NJEGOVIH ADICIONIH SOLI SA FARMACEUTSKI PRIHVATLJIVOM KISELINOMInfo
- Publication number
- ME00814B ME00814B MEP-2009-230A MEP23009A ME00814B ME 00814 B ME00814 B ME 00814B ME P23009 A MEP23009 A ME P23009A ME 00814 B ME00814 B ME 00814B
- Authority
- ME
- Montenegro
- Prior art keywords
- formula
- compound
- synthesis
- reaction
- acid
- Prior art date
Links
- 230000015572 biosynthetic process Effects 0.000 title claims abstract 24
- 238000003786 synthesis reaction Methods 0.000 title claims abstract 24
- 239000002253 acid Substances 0.000 title claims abstract 5
- ACRHBAYQBXXRTO-OAQYLSRUSA-N ivabradine Chemical compound C1CC2=CC(OC)=C(OC)C=C2CC(=O)N1CCCN(C)C[C@H]1CC2=C1C=C(OC)C(OC)=C2 ACRHBAYQBXXRTO-OAQYLSRUSA-N 0.000 title claims abstract 4
- 229960003825 ivabradine Drugs 0.000 title claims abstract 4
- 238000000034 method Methods 0.000 title claims 23
- 150000007513 acids Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract 46
- 150000003839 salts Chemical class 0.000 claims abstract 3
- 150000004677 hydrates Chemical class 0.000 claims abstract 2
- 238000006243 chemical reaction Methods 0.000 claims 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims 6
- 238000007363 ring formation reaction Methods 0.000 claims 5
- WUAXWQRULBZETB-UHFFFAOYSA-N homoveratric acid Chemical compound COC1=CC=C(CC(O)=O)C=C1OC WUAXWQRULBZETB-UHFFFAOYSA-N 0.000 claims 4
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims 4
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 3
- VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 claims 3
- CZLMRJZAHXYRIX-UHFFFAOYSA-N 1,3-dioxepane Chemical compound C1CCOCOC1 CZLMRJZAHXYRIX-UHFFFAOYSA-N 0.000 claims 3
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims 3
- 229910052799 carbon Inorganic materials 0.000 claims 3
- 125000004432 carbon atom Chemical group C* 0.000 claims 3
- 239000003960 organic solvent Substances 0.000 claims 3
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 claims 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims 2
- 230000002378 acidificating effect Effects 0.000 claims 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims 2
- 239000002904 solvent Substances 0.000 claims 2
- LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical class CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 claims 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 claims 1
- 150000000996 L-ascorbic acids Chemical class 0.000 claims 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical class [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 claims 1
- 235000010323 ascorbic acid Nutrition 0.000 claims 1
- 150000008107 benzenesulfonic acids Chemical class 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 claims 1
- 239000003153 chemical reaction reagent Substances 0.000 claims 1
- 229910052801 chlorine Inorganic materials 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 235000015165 citric acid Nutrition 0.000 claims 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid group Chemical class C(CC(O)(C(=O)O)CC(=O)O)(=O)O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims 1
- 238000006482 condensation reaction Methods 0.000 claims 1
- 239000007822 coupling agent Substances 0.000 claims 1
- 235000011087 fumaric acid Nutrition 0.000 claims 1
- 150000002238 fumaric acids Chemical class 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 125000002883 imidazolyl group Chemical group 0.000 claims 1
- 238000002955 isolation Methods 0.000 claims 1
- 239000004310 lactic acid Substances 0.000 claims 1
- 235000014655 lactic acid Nutrition 0.000 claims 1
- 150000002689 maleic acids Chemical class 0.000 claims 1
- 235000006408 oxalic acid Nutrition 0.000 claims 1
- 150000002913 oxalic acids Chemical class 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 1
- 229940107700 pyruvic acid Drugs 0.000 claims 1
- 235000002906 tartaric acid Nutrition 0.000 claims 1
- 150000003512 tertiary amines Chemical class 0.000 claims 1
- 238000001308 synthesis method Methods 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/16—Benzazepines; Hydrogenated benzazepines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- 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
-
- 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
- A61P9/06—Antiarrhythmics
-
- 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
- A61P9/08—Vasodilators for multiple indications
-
- 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
- A61P9/10—Drugs 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/18—Dibenzazepines; Hydrogenated dibenzazepines
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
Postupak sinteze jedinjenja formule (I): Primena u sintezi ivabradina, njegove adicione soli sa farmaceutski prihvatljivom kiselinom i njegovih hidrata.
Claims (21)
1.Postupak za sintezu jedinjenja formule (I): koji se karakteriše time što se (3,4-dimetoksifenil)sirćetna kiselina formule (IV): prevodi u jedinjenje formule (V): u kojoj grupe R1 i R2, koje mogu biti iste ili različite, predstavljaju linearne ili razgranate (C1-C6)alkoksi grupe, ili, zajedno sa atomom ugljenika, koji ih nosi, obrazuju prsten 1 ,3-dioksana, 1 ,3-dioksolana ili 1,3-dioksepana, koje se podvrgava reakciji ciklizacije u kiselom medijumu kako bi se dobilo, nakon izolovanja, jedinjenje formule (1).
2.Postupak sinteze, kao u patentnom zahtevu 1, naznačen time što se prevođenje jedinjenja formule (IV) u jedinjenje formule (V) izvodi putem preliminarnog prevođenja jedinjenja formule (IV) u jedinjenje formule (Vl): u kojoj X predstavlja atom halogena ili OCOR3 grupu u kojoj je R3 linearna ili razgranata (C1C6)alkil grupa, fenil grupa, benzil grupa ili imidazolska grupa, u organskom rastvaraču, i, zatim se jedinjenje formule (Vl) podvrgava reakciji kondenzacije sa jedinjenjem formule (VII): u kojoj grupe R1 i R2, koje mogu biti iste ili različite, predstavljaju linearne ili razgranate (C1-C6)alkoksi grupe, ili, zajedno sa atomom ugljenika, koji ih nosi, obrazuju prsten 1,3-dioksana, 1,3-dioksolana ili 1,3-dioksepana, u prisustvu baze u organskom rastvaraču, kako bi se dobilo jedinjenje formule (V):
3.Postupak sinteze, kao u patentnom zahtevu 1, naznačen time što se prevođenje jedinjenja formule (IV) u jedinjenje formule (V) se izvodi reakcijom sa jedinjenjem formule (VII): u kojoj grupe R1 i R2, koje mogu biti iste ili različite, predstavljaju linearne ili razgranate (C1-C6)alkoksi grupe, ili, zajedno sa atomom ugljenika, koji ih nosi, obrazuju prsten 1,3-dioksana, 1,3-dioksolana ili 1 ,3-dioksepana, u prisustvu kuplujućeg agensa u organskom rastvaraču, kako bi se dobilo jedinjenje formule (V):
4.Postupak za sintezu, kao u patentnom zahtevu 2, naznačen time što se jedinjenja formule (V) i (Vl) ne izoluju.
5.Postupak za sintezu, kao u patentnom zahtevu 3, naznačen time što se jedinjenje formule (V) ne izoluje.
6.Postupak za sintezu, kao u patentnom zahtevu ili 2 ili 4, naznačen time što u jedinjenju formule (Vl), X predstavlja atom hlora.
7.Postupak sinteze, kao u bilo kom od patentnih zahteva 2, 4 ili 6, naznačen time što je korišćeni rastvarač za prevođenje jedinjenja formule (IV) u jedinjenje formule (Vl) dihlorometan.
8.Postupak sinteze, kao u bilo kom od patentnih zahteva 2, 4, 6 ili 7, naznačen time što je temperatura reakcije za konverziju jedinjenja formule (IV) u jedinjenje formule (Vl) od 20 do 40°C.
9.Postupak sinteze, kao u bilo kom od patentnih zahteva 2, 4, 6 do 8, naznačen time što je reagens upotrebljen za konverziju jedinjenja formule (IV) u jedinjenje formule (Vl) tionil hlorid.
10.Postupak sinteze, kao u patentnom zahtevu 9, naznačen time što je količina tionil hlorida upotrebljenog u reakciji konverzije jedinjenja formule (IV) u jedinjenje formule (Vl) od 1 do 1.3 mola po molu jedinjenja formule (IV).
11.Postupak sinteze, kao u bilo kom od patentnih zahteva 2, 4 ili 6 do 1 O, naznačen time što je rastvarač za reakciju između jedinjenja formule (Vl) i jedinjenja formule (VII) dihlorometan.
12.Postupak sinteze, kao u bilo kom od patentnih zahteva 2, 4 ili 6 do 1 1 , naznačen time što je tempe ratura reakcije između jedinjenja formule (Vl) i jedinjenja formule (VII) od 0 do 40°C.
13.Postupak sinteze, kao u bilo kom od patentnih zahteva 2, 4 ili 6 do 12, naznačen time što je količina jedinjenja (VII) upotrebljenog u reakciji sa jedinjenjem formule (Vl) od 1 do 1.2 mola po molu jedinjenja formule (Vl).
14.Postupak sinteze, kao u bilo kom od patentnih zahteva 2, 4 ili 6 do 13, naznačen time što je količina baze upotrebljene u reakciji između jedinjenja formule (Vl) i (VII) od 1 do 1.3 mola po molu jedinjenja formule (Vl).
15.Postupak sinteze, kao u bilo kom od patentnih zahteva 2, 4 ili 6 do 14, naznačen time što je baza upotrebljena u reakciji između jedinjenja formule (Vl) i (VII) piridin, DMAP ili tercijerni amin.
16.Postupak sinteze, kao u patentnom zahtevu 15, naznačen time što je baza upotrebljena u reakciji između jedinjenja formule (Vl) i (VII) trietilamin.
17.Postupak sinteze, kao u bilo kom od patentnih zahteva 1 do 16, naznačen time što je količina kiseline upotrebljene u reakciji ciklizacije jedinjenja formule M od 5 do 15 mola po molu jedinjenja formule (V).
18.Postupak sinteze, kao u bilo kom od patentnih zahteva 1 do 17, naznačen time što je temperatura reakcije ciklizacije jedinjenja formule (V) u kiselom medijumu od 0 do 40°C.
19.Postupak sinteze, kao u bilo kom od patentnih zahteva 1 do 18, naznačen time što je kiselina upotrebljena za ciklizaciju jedinjenja formule M koncentrovana sumporna kiselina.
20.Postupak sinteze, kao u patentnim zahtevima 4 ili 5 i 19, naznačen time što je količina koncentrovane sumporne kiseline upotrebljene u reakciji ciklizacije jedinjenja formule (V) od 1. 5 do 3 mililitra po gramu (3,4-dimetoksifenil)sirćetne kiseline formule (IV).
21.Postupak za sintezu ivabradina i njegovih farmaceutski prihvatljivih soli, u kome se jedinjenje formule (IV) prevodi u jedinjenje formule (l) u skladu sa postupkom iz patentnog zahteva 1, a zatim se, jedinjenje formule (l) prevodi u ivabradin, koji se opciono može prevesti u svoje adicione soli sa farmaceutski prihvatljivom kiselinom, koja je odabrana od: hlorovodonične kiseline, bromovodonične kiseline, sumporne kiseline, fosforne kiseline, sirćetne kiseline, tritluorosirćetne kiseline, mlečne kiseline, piruvatne kiseline, malonske kiseline, ćilibarne kiseline, glutarne kiseline, fumarne kiseline, vinske kiseline, maleinske kiseline, limunske kiseline, askorbinske kiseline, oksalne kiseline, metansulfonske kiseline, benzensulfonska kiseline i kamforne kiseline i, u svoje hidrate.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0803452A FR2932800B1 (fr) | 2008-06-20 | 2008-06-20 | Nouveau procede de synthese de la 7,8-dimethoxy-1,3-dihydro- 2h-3-benzazepin-2-one, et application a la synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ME00814B true ME00814B (me) | 2012-03-20 |
Family
ID=40347797
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MEP-2009-230A ME00814B (me) | 2008-06-20 | 2009-06-18 | NOVI POSTUPAK SINTEZE 7,8-DIMETOKSI-1 ,3-DIHIDR0-2H-3-BENZAZEPIN-2-ON-a l PRIMENA U SINTEZI IVABRADINA l NJEGOVIH ADICIONIH SOLI SA FARMACEUTSKI PRIHVATLJIVOM KISELINOM |
Country Status (35)
| Country | Link |
|---|---|
| US (1) | US7928223B2 (me) |
| EP (1) | EP2135861B2 (me) |
| JP (1) | JP5216697B2 (me) |
| KR (1) | KR101119296B1 (me) |
| CN (1) | CN101607939B (me) |
| AR (1) | AR072175A1 (me) |
| AU (1) | AU2009202314B2 (me) |
| BR (1) | BRPI0902105A2 (me) |
| CA (1) | CA2668524C (me) |
| CL (1) | CL2009001414A1 (me) |
| CY (1) | CY1115623T1 (me) |
| DK (1) | DK2135861T4 (me) |
| EA (1) | EA017333B1 (me) |
| ES (1) | ES2522625T5 (me) |
| FR (1) | FR2932800B1 (me) |
| GE (1) | GEP20125407B (me) |
| HR (1) | HRP20140928T4 (me) |
| JO (1) | JO3806B1 (me) |
| MA (1) | MA31071B1 (me) |
| ME (1) | ME00814B (me) |
| MX (1) | MX2009006288A (me) |
| MY (1) | MY146245A (me) |
| NZ (1) | NZ577540A (me) |
| PE (1) | PE20100051A1 (me) |
| PL (1) | PL2135861T5 (me) |
| PT (1) | PT2135861E (me) |
| RS (1) | RS53495B2 (me) |
| SA (1) | SA109300396B1 (me) |
| SG (1) | SG158026A1 (me) |
| SI (1) | SI2135861T2 (me) |
| TW (1) | TWI374134B (me) |
| UA (1) | UA107779C2 (me) |
| UY (1) | UY31883A (me) |
| WO (1) | WO2009153461A2 (me) |
| ZA (1) | ZA200904316B (me) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101478855B1 (ko) * | 2007-05-30 | 2015-01-02 | 인드-스위프트 래버러토리즈 리미티드 | 이바브라딘 히드로클로라이드 및 그의 다형태의 제조방법 |
| CN101774969B (zh) * | 2009-01-13 | 2012-07-04 | 江苏恒瑞医药股份有限公司 | 硫酸伊伐布雷定及其i型结晶的制备方法 |
| SI23290A (sl) | 2010-02-12 | 2011-08-31 | Krka D.D., Novo Mesto | Nove oblike ivabradin hidroklorida |
| FR2956401B1 (fr) | 2010-02-17 | 2012-02-03 | Servier Lab | Nouveau procede de synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable |
| WO2011104723A2 (en) * | 2010-02-23 | 2011-09-01 | Ind-Swift Laboratories Limited | Acid addition salts of ivabradine and preparation thereof |
| HUP1000245A2 (en) * | 2010-05-07 | 2011-11-28 | Richter Gedeon Nyrt | Industrial process for the production ivabradin salts |
| FR2984320B1 (fr) * | 2011-12-20 | 2013-11-29 | Servier Lab | Nouveau procede de synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable |
| FR3003859B1 (fr) * | 2013-03-26 | 2015-03-13 | Servier Lab | "procede de synthese de derives de la 7,8-dimethoxy-1,3-dihydro-2h-3-benzazepin-2-one et application a la synthese de l'ivabradine" |
| HU230826B1 (hu) * | 2014-11-19 | 2018-07-30 | Richter Gedeon Nyrt. | Eljárás benzazepin származékok előállítására |
| EP3101010A1 (en) | 2015-06-03 | 2016-12-07 | Urquima S.A. | New method for the preparation of highly pure ivabradine base and salts thereof |
| CN108424389A (zh) * | 2017-02-13 | 2018-08-21 | 浙江京新药业股份有限公司 | 一种伊伐布雷定杂质的制备方法 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4490369A (en) * | 1981-05-19 | 1984-12-25 | Dr. Karl Thomae Gesellschaft Mit Beschrankter Haftung | Benzazepine derivatives, their pharmaceutical compositions and method of use |
| NZ207007A (en) * | 1983-02-04 | 1985-08-30 | Lilly Co Eli | Benzazepine derivatives and pharmaceutical compositions |
| DE3343801A1 (de) * | 1983-12-03 | 1985-06-13 | Dr. Karl Thomae Gmbh, 7950 Biberach | Neue indolderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| DE3418271A1 (de) * | 1984-05-17 | 1985-11-21 | Dr. Karl Thomae Gmbh, 7950 Biberach | Neue benzazepinderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| DE3418270A1 (de) * | 1984-05-17 | 1985-11-21 | Dr. Karl Thomae Gmbh, 7950 Biberach | Neue aminotetralinderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| EP0204349A3 (de) * | 1985-06-01 | 1990-01-03 | Dr. Karl Thomae GmbH | Neue heteroaromatische Aminderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
| FR2681862B1 (fr) * | 1991-09-27 | 1993-11-12 | Adir Cie | Nouvelles (benzocycloalkyl)alkylamines, leur procede de preparation, et les compositions pharmaceutiques qui les contiennent. |
| UA77165C2 (en) * | 2000-11-17 | 2006-11-15 | Lilly Co Eli | (n)-((s)-2-hydroxy-3-methyl-butyryl)-1-(l-alaninyl)-(s)-1-amino-3-methyl-4,5,6,7-tetrahydro-2h-3-benzazepin-2-one dihydrate, processes for manufacturing and pharmaceutical composition |
| JPWO2002074746A1 (ja) * | 2001-03-16 | 2004-07-08 | 山之内製薬株式会社 | ベンゾアゼピン誘導体 |
| WO2005039591A1 (en) * | 2003-10-23 | 2005-05-06 | F. Hoffmann-La Roche Ag | Benzazepine derivatives as mao-b inhibitors |
| FR2868777B1 (fr) * | 2004-04-13 | 2006-05-26 | Servier Lab | Nouveau procede de synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable |
| ZA200800440B (en) * | 2005-07-15 | 2009-12-30 | Amr Technology Inc | Aryl-and heteroaryl-substituted tetrahydrobenzazepines and use thereof to block reuptake of norepinephrine, dopamine, and serotonin |
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