HRP20150924T1 - Postupak sinteze derivata 7,8-dimetoksi-1,3-dihidro-2h-3-benzazepin-2-ona i njihova uporaba za pripravu ivabradina - Google Patents
Postupak sinteze derivata 7,8-dimetoksi-1,3-dihidro-2h-3-benzazepin-2-ona i njihova uporaba za pripravu ivabradina Download PDFInfo
- Publication number
- HRP20150924T1 HRP20150924T1 HRP20150924TT HRP20150924T HRP20150924T1 HR P20150924 T1 HRP20150924 T1 HR P20150924T1 HR P20150924T T HRP20150924T T HR P20150924TT HR P20150924 T HRP20150924 T HR P20150924T HR P20150924 T1 HRP20150924 T1 HR P20150924T1
- Authority
- HR
- Croatia
- Prior art keywords
- formula
- compound
- image
- acid
- synthesis
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims 10
- 230000015572 biosynthetic process Effects 0.000 title claims 9
- 238000003786 synthesis reaction Methods 0.000 title claims 9
- 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 3
- 229960003825 ivabradine Drugs 0.000 title claims 3
- 238000002360 preparation method Methods 0.000 title claims 2
- CPNZASIAJKSBBH-UHFFFAOYSA-N 7,8-dimethoxy-1,3-dihydro-3-benzazepin-2-one Chemical class C1C(=O)NC=CC2=C1C=C(OC)C(OC)=C2 CPNZASIAJKSBBH-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 36
- 239000003960 organic solvent Substances 0.000 claims 7
- 238000006722 reduction reaction Methods 0.000 claims 7
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims 3
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-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
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-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
- 239000003513 alkali Substances 0.000 claims 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims 1
- LSPHULWDVZXLIL-UHFFFAOYSA-N Camphoric acid Natural products CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 claims 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-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 Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims 1
- 239000011668 ascorbic acid Substances 0.000 claims 1
- 235000010323 ascorbic acid Nutrition 0.000 claims 1
- 229960005070 ascorbic acid Drugs 0.000 claims 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims 1
- 229940092714 benzenesulfonic acid Drugs 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
- LSPHULWDVZXLIL-QUBYGPBYSA-N camphoric acid Chemical compound CC1(C)[C@H](C(O)=O)CC[C@]1(C)C(O)=O LSPHULWDVZXLIL-QUBYGPBYSA-N 0.000 claims 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 235000015165 citric acid Nutrition 0.000 claims 1
- 239000007822 coupling agent Substances 0.000 claims 1
- 239000001530 fumaric acid Substances 0.000 claims 1
- 235000011087 fumaric acid Nutrition 0.000 claims 1
- 239000004220 glutamic acid Substances 0.000 claims 1
- 235000013922 glutamic acid Nutrition 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 150000004677 hydrates Chemical class 0.000 claims 1
- 239000004310 lactic acid Substances 0.000 claims 1
- 235000014655 lactic acid Nutrition 0.000 claims 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims 1
- 239000011976 maleic acid Substances 0.000 claims 1
- 229940098779 methanesulfonic acid Drugs 0.000 claims 1
- -1 methoxybenzyl group Chemical group 0.000 claims 1
- 235000006408 oxalic acid Nutrition 0.000 claims 1
- 229940107700 pyruvic acid Drugs 0.000 claims 1
- 238000007363 ring formation reaction Methods 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
- 239000011975 tartaric acid Substances 0.000 claims 1
- 235000002906 tartaric acid Nutrition 0.000 claims 1
- 125000005490 tosylate group Chemical group 0.000 claims 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/32—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
- C07C235/34—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/06—One of the condensed rings being a six-membered aromatic ring the other ring being four-membered
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
Claims (11)
1. Postupak za sintezu spoja formule (I):
[image]
pri čemu R predstavlja para-metoksibenzilnu (PMB) skupinu ili sljedeću skupinu:
[image]
naznačen time, da je spoj formule (VII):
[image]
pri čemu je R definiran kako je gore navedeno,
izložen je redukcijskoj reakciji,
u nazočnosti LiBH(Et)3,
u organskom otapalu,
kako bi se dobio spoj formule (I).
2. Postupak za sintezu u skladu s patentnim zahtjevom 1, naznačen time, da količina LiBH(Et)3 koja se koristi u izvođenju redukcijske reakcije na spoju formule (VII) pri čemu nastaje spoj formule (I) je od 1 do 3 ekvivalenta.
3. Postupak za sintezu u skladu s bilo kojim patentnim zahtjevom 1 ili 2, naznačen time, da je organsko otapalo koje je korišteno u redukcijskoj reakciji na spoju formule (VII) pri čemu nastaje spoj formule (I) odabrano od tetrahidrofurana (THF), metil tetrahidrofurana (MeTHF), diklorometana, toluena i diizopropil etera.
4. Postupak za sintezu u skladu s patentnim zahtjevom 3, naznačen time, da organsko otapalo koje se koristi u izvođenju redukcijske reakcije na spoju formule (VII) pri čemu nastaje spoj formule (I) je tetrahidrofuran.
5. Postupak za sintezu u skladu s bilo kojim od patentnih zahtjeva 1 do 4, naznačen time, da se redukcijska reakcija na spoju formule (VII) pri čemu nastaje spoj formule (I) izvodi pri temperaturi od -100 °C do 20°C.
6. Postupak za sintezu ivabradina formule (II), u skladu s patentnim zahtjevom 1, pri čemu R predstavlja sljedeću skupinu:
[image]
naznačen time, da spoj formule (VIII), poseban slučaj spojeva formule (VII):
[image]
izložen redukcijskoj reakciji sukladno patentnom zahtjevu 1 kako bi se dobio spoj formule (VI), poseban slučaj spojeva formule (I):
[image]
a potom se spoj formule (VI) izlaže katalitičkoj hidrogenaciji kako bi se dobio ivabradin formule (II):
[image]
koji se može pretvoriti u njihovu adicijsku sol s farmaceutski prihvatljivom kiselinom odabranom od klorovodične kiseline, bromovodične kiseline, sumporne kiseline, fosforne kiseline, octene kiseline, trifluoroctene kiseline, mliječne kiseline, pirogroždane kiseline, malonske kiseline, sukcinske kiseline, glutame kiseline, fumame kiseline, vinske kiseline, maleinske kiseline, limunske kiseline, askorbinske kiseline, oksalne kiseline, metansulfonske kiseline, benzensulfonske kiseline i kamfome kiseline, i u njihove hidrate.
7. Postupak za sintezu u skladu s patentnim zahtjevom 6, naznačen time, da se spoj formule (VIII) pripravlja počevši od spoja formule (IX):
[image]
koji reagira sa spojem formule (X):
[image]
pri čemu X predstavlja atom halogena, mesilatnu skupinu ili tosilatnu skupinu, u nazočnosti lužine, u organskom otapalu, kako bi se dobio spoj formule (VIII):
[image]
8. Postupak za sintezu u skladu s patentnim zahtjevom 6, naznačen time, da je spoj formule (VIII) pripravljen počevši od spoja formule (XI):
[image]
koji se pretvara u spoj formule (XII):
[image]
u nazočnosti sredstva za povezivanje, u organskom otapalu,
rečeni spoj formule (XII) potom reagira sa spojem formule (XIII):
[image]
u nazočnosti lužine,
u organskom otapalu,
kako bi se dobio spoj formule (XIV):
[image]
koji se izlaže reakciji ciklizacije u nazočnosti sredstva za povezivanje,
u organskom otapalu,
kako bi se dobio spoj formule (VIII):
[image]
9. Postupak u skladu s patentnim zahtjevom 1, pri čemu R predstavlja para metoksibenzilnu skupinu, za pripravu spoja formule (XV):
[image]
naznačen time, da je spoj formule (XVI), poseban slučaj spojeva formule (VII):
[image]
izložen redukcijskoj reakciji u skladu s patentnim zahtjevom 1 kako bi se dobio spoj formule (XVII), poseban slučaj spojeva formule (I):
[image]
a potom se spoju formule (XVII) skida zaštita kako bi se dobio spoj formule (XV).
10. Spoj formule (VIII):
[image]
11. Spoj formule (XIV):
[image]
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR1352741A FR3003859B1 (fr) | 2013-03-26 | 2013-03-26 | "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" |
EP14161388.5A EP2784066B1 (fr) | 2013-03-26 | 2014-03-25 | Procédé de synthèse de dérivés de la 7,8-dimethoxy-1,3-dihydro-2H-3-benzazépin-2-one et application à la synthèse de l'ivabradine |
Publications (1)
Publication Number | Publication Date |
---|---|
HRP20150924T1 true HRP20150924T1 (hr) | 2015-10-09 |
Family
ID=48613923
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HRP20150924TT HRP20150924T1 (hr) | 2013-03-26 | 2015-09-03 | Postupak sinteze derivata 7,8-dimetoksi-1,3-dihidro-2h-3-benzazepin-2-ona i njihova uporaba za pripravu ivabradina |
Country Status (37)
Country | Link |
---|---|
US (1) | US8927708B2 (hr) |
EP (1) | EP2784066B1 (hr) |
JP (1) | JP5732159B2 (hr) |
KR (1) | KR101616434B1 (hr) |
CN (1) | CN104072420B (hr) |
AR (1) | AR095722A1 (hr) |
AU (1) | AU2014201355B2 (hr) |
BR (1) | BR102014007079A2 (hr) |
CA (1) | CA2846917C (hr) |
CY (1) | CY1116535T1 (hr) |
DK (1) | DK2784066T3 (hr) |
EA (1) | EA025516B1 (hr) |
ES (1) | ES2548713T3 (hr) |
FR (1) | FR3003859B1 (hr) |
GE (1) | GEP201706731B (hr) |
HK (2) | HK1198366A1 (hr) |
HR (1) | HRP20150924T1 (hr) |
HU (1) | HUE025550T2 (hr) |
IN (1) | IN2014DE00793A (hr) |
JO (1) | JO3132B1 (hr) |
MA (1) | MA35509B1 (hr) |
MD (1) | MD4461C1 (hr) |
ME (1) | ME02213B (hr) |
MX (1) | MX346640B (hr) |
MY (1) | MY189537A (hr) |
NZ (1) | NZ622915A (hr) |
PL (1) | PL2784066T3 (hr) |
PT (1) | PT2784066E (hr) |
RS (1) | RS54186B1 (hr) |
SA (1) | SA114350383B1 (hr) |
SG (1) | SG10201400610SA (hr) |
SI (1) | SI2784066T1 (hr) |
TW (1) | TWI511957B (hr) |
UA (1) | UA116527C2 (hr) |
UY (1) | UY35503A (hr) |
WO (1) | WO2014154994A1 (hr) |
ZA (1) | ZA201402072B (hr) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104610146A (zh) * | 2015-01-23 | 2015-05-13 | 常州大学 | 一种3-氮杂二环[5,1,0]-7-醛及合成方法 |
Family Cites Families (16)
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 |
DE3119874A1 (de) * | 1981-05-19 | 1982-12-09 | Dr. Karl Thomae Gmbh, 7950 Biberach | "benzazepinderivate, ihre herstellung und ihre verwendung als arzneimittel" |
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 |
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 |
DE3519735A1 (de) * | 1985-06-01 | 1986-12-04 | Dr. Karl Thomae Gmbh, 7950 Biberach | 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. |
FR2868775B1 (fr) * | 2004-04-13 | 2008-04-11 | Servier Lab | Nouveau procede de synthese de derives de la 1,3,4,5- tetrahydro-2h-3-benzazepin-2-one, et application a la synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable |
FR2870537A1 (fr) * | 2004-05-19 | 2005-11-25 | Servier Lab | Nouveau procede de synthese du (1s)-4,5-dimethoxy-1-(methyl aminomethyl-)-benzocyclobutane et de ses sels d'addition, et application a la synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable |
GB0412314D0 (en) * | 2004-06-02 | 2004-07-07 | Glaxo Group Ltd | Compounds |
US8312771B2 (en) | 2006-11-10 | 2012-11-20 | Siemens Medical Solutions Usa, Inc. | Transducer array imaging system |
ES2381771T3 (es) * | 2006-11-30 | 2012-05-31 | Cadila Healthcare Limited | Procedimiento para la preparación de hidrocloruro de ivabradina |
FR2920773B1 (fr) * | 2007-09-11 | 2009-10-23 | Servier Lab | Derives de 1,2,4,5-tetrahydro-3h-benzazepines, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
CN101343249A (zh) * | 2008-06-10 | 2009-01-14 | 上海医药工业研究院 | 3-(3-氯丙基)-7,8-二甲氧基-1,3-二氢-2h-3-苯并氮杂-2-酮的制备方法 |
FR2932800B1 (fr) * | 2008-06-20 | 2015-02-20 | Servier Lab | 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 |
FR2941695B1 (fr) * | 2009-02-04 | 2011-02-18 | Servier Lab | Nouveau procede de synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable |
-
2013
- 2013-03-26 FR FR1352741A patent/FR3003859B1/fr not_active Expired - Fee Related
-
2014
- 2014-03-11 MY MYPI2014700574A patent/MY189537A/en unknown
- 2014-03-11 AU AU2014201355A patent/AU2014201355B2/en not_active Ceased
- 2014-03-13 SG SG10201400610SA patent/SG10201400610SA/en unknown
- 2014-03-13 MA MA36830A patent/MA35509B1/fr unknown
- 2014-03-16 JO JOP/2014/0112A patent/JO3132B1/ar active
- 2014-03-18 IN IN793DE2014 patent/IN2014DE00793A/en unknown
- 2014-03-19 CA CA2846917A patent/CA2846917C/fr not_active Expired - Fee Related
- 2014-03-19 MX MX2014003347A patent/MX346640B/es active IP Right Grant
- 2014-03-20 MD MDA20140028A patent/MD4461C1/ro not_active IP Right Cessation
- 2014-03-20 ZA ZA2014/02072A patent/ZA201402072B/en unknown
- 2014-03-21 GE GEAP201413425A patent/GEP201706731B/en unknown
- 2014-03-24 US US14/223,143 patent/US8927708B2/en not_active Expired - Fee Related
- 2014-03-24 UA UAA201402995A patent/UA116527C2/uk unknown
- 2014-03-24 UY UY0001035503A patent/UY35503A/es unknown
- 2014-03-24 TW TW103110914A patent/TWI511957B/zh not_active IP Right Cessation
- 2014-03-25 EP EP14161388.5A patent/EP2784066B1/fr active Active
- 2014-03-25 WO PCT/FR2014/050690 patent/WO2014154994A1/fr active Application Filing
- 2014-03-25 ES ES14161388.5T patent/ES2548713T3/es active Active
- 2014-03-25 DK DK14161388.5T patent/DK2784066T3/en active
- 2014-03-25 RS RS20150527A patent/RS54186B1/en unknown
- 2014-03-25 KR KR1020140034869A patent/KR101616434B1/ko not_active IP Right Cessation
- 2014-03-25 JP JP2014061183A patent/JP5732159B2/ja active Active
- 2014-03-25 SA SA114350383A patent/SA114350383B1/ar unknown
- 2014-03-25 EA EA201400269A patent/EA025516B1/ru not_active IP Right Cessation
- 2014-03-25 AR ARP140101337A patent/AR095722A1/es unknown
- 2014-03-25 PL PL14161388T patent/PL2784066T3/pl unknown
- 2014-03-25 ME MEP-2015-152A patent/ME02213B/me unknown
- 2014-03-25 PT PT141613885T patent/PT2784066E/pt unknown
- 2014-03-25 HU HUE14161388A patent/HUE025550T2/en unknown
- 2014-03-25 SI SI201430005T patent/SI2784066T1/sl unknown
- 2014-03-25 NZ NZ622915A patent/NZ622915A/en not_active IP Right Cessation
- 2014-03-25 BR BR102014007079A patent/BR102014007079A2/pt not_active Application Discontinuation
- 2014-03-26 CN CN201410130182.4A patent/CN104072420B/zh not_active Expired - Fee Related
- 2014-11-24 HK HK14111868A patent/HK1198366A1/xx not_active IP Right Cessation
-
2015
- 2015-03-23 HK HK15102942.8A patent/HK1202532A1/xx unknown
- 2015-07-23 CY CY20151100650T patent/CY1116535T1/el unknown
- 2015-09-03 HR HRP20150924TT patent/HRP20150924T1/hr unknown
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
HRP20200715T1 (hr) | Postupak proizvodnje n-[(3-aminooksetan-3-il) metil]-2-(1,1-diokso-3,5-dihidro-1,4-benzotiazepin-4-il)-6-metil-kinazolin-4-amina | |
HRP20211777T1 (hr) | Postupak u jednoj posudi za pripremu racemičnog nikotina reakcijom etil nikotinata s n-vinilpirolidonom u prisutnosti natrij etanolata ili kalij etanolata ili njihovih mješavina | |
HRP20211072T1 (hr) | Sinteza indazola | |
HRP20170851T1 (hr) | Postupak za proizvodnju cikloalkilkarboksiamido-piridin benzojevih kiselina | |
MX2015015893A (es) | 2-fenilimidazo[1,2-a]pirimidinas como agentes formadores de imagen. | |
RS54848B1 (sr) | Nova pesticidna jedinjenja na bazi pirazola | |
HRP20150947T1 (hr) | Inhibitori fosfoinositid 3-kinaze sa skupinom koja veže cink | |
HRP20100260T1 (hr) | Postupak za proizvodnju stroncij ranelata i njegovih hidrata | |
HRP20140928T4 (hr) | Postupak za pripravu 7,8-dimetoksi-1,3-dihidro-2h-3-benzazepin-2-ona, te njegove primjene u sintezi ivabradina i njegovih adicijskih soli s farmaceutski prihvatljivom kiselinom | |
HRP20170621T1 (hr) | Postupak za pripremanje derivata piperazinil i diazepanil benzamida | |
CN103772278A (zh) | 一种重要四氢异喹啉衍生物中间体及其合成方法 | |
RS53964B1 (en) | MACROCYCLIC UNITS AND PROCEDURES FOR THEIR PRODUCTION | |
HRP20150924T1 (hr) | Postupak sinteze derivata 7,8-dimetoksi-1,3-dihidro-2h-3-benzazepin-2-ona i njihova uporaba za pripravu ivabradina | |
HRP20150899T1 (hr) | Postupak za jodiranje fenolnih derivata | |
HRP20211994T1 (hr) | Postupak i intermedijeri za dobivanje bilastina | |
SI2681192T1 (en) | Synthesis of the 2-carboxamide cycloamino derivatives derivatives | |
CN106699739B (zh) | 3-吲哚-4-吲唑马来酰亚胺类化合物及其制备方法和应用 | |
HRP20201638T1 (hr) | Postupci pripreme spojeva alkiliranog arilpiperazina i alkaliziranog arilpiperidina uključujući nove međuspojeve | |
RS52699B (en) | NEW PROCEDURE FOR THE SYNTHESIS OF IVABRADINE AND ITS ADDITIONAL SALTS WITH PHARMACEUTICALLY ACCEPTABLE ACID | |
HRP20110915T1 (hr) | Postupak za sintezu ivabradina i njegove farmaceutski prihvatljive kisele adicijske soli | |
TN2011000598A1 (en) | Process for the preparation of a compositon comprising meso-tartaric acid | |
CL2012000159A1 (es) | Procedimiento para la preparacion estereoselectiva de compuestos (trans)- y (cis)-9-[4-(3-cloro-2-fluoro-fenilamino)-7-metoxi-quinazolin-6-iloxi]-1,4-diaza-espiro[5.5]undecan-5-ona, y los compuestos intermediarios considerados. | |
CN103508898B (zh) | 一种新的枸橼酸阿尔维林的制备方法 | |
RS52529B (en) | A NEW PROCEDURE FOR THE SYNTHESIS OF IVABRADINE AND ITS ADDED SALTS | |
CN105367571B (zh) | 一种米氮平的合成方法 |