ME02636B - Postupak za sintezu 3,4-dimetoksibiciklo[4.2.0]okta-1,3,5-trien-7-karbonitrila i uporaba za sintezu ivabradina i njegovih adicijskih soli s farmaceutski prihvatljivom kiselinom - Google Patents
Postupak za sintezu 3,4-dimetoksibiciklo[4.2.0]okta-1,3,5-trien-7-karbonitrila i uporaba za sintezu ivabradina i njegovih adicijskih soli s farmaceutski prihvatljivom kiselinomInfo
- Publication number
- ME02636B ME02636B MEP-2017-64A MEP201764A ME02636B ME 02636 B ME02636 B ME 02636B ME P201764 A MEP201764 A ME P201764A ME 02636 B ME02636 B ME 02636B
- Authority
- ME
- Montenegro
- Prior art keywords
- compound
- formula
- conversion
- process according
- vii
- Prior art date
Links
- 230000015572 biosynthetic process Effects 0.000 title claims 4
- 238000003786 synthesis reaction Methods 0.000 title claims 4
- 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
- 150000003839 salts Chemical class 0.000 title claims 2
- YQNZTZCPUODXTN-UHFFFAOYSA-N 8,8-dimethoxybicyclo[4.2.0]octa-1,3,5-triene-7-carbonitrile Chemical compound COC1(C(C2=CC=CC=C12)C#N)OC YQNZTZCPUODXTN-UHFFFAOYSA-N 0.000 title 1
- 239000002253 acid Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 38
- 238000000034 method Methods 0.000 claims 18
- 238000006243 chemical reaction Methods 0.000 claims 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims 6
- 239000003960 organic solvent Substances 0.000 claims 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims 3
- 239000003513 alkali Substances 0.000 claims 3
- 150000002902 organometallic compounds Chemical class 0.000 claims 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims 3
- CFOAUYCPAUGDFF-UHFFFAOYSA-N tosmic Chemical compound CC1=CC=C(S(=O)(=O)C[N+]#[C-])C=C1 CFOAUYCPAUGDFF-UHFFFAOYSA-N 0.000 claims 3
- VTGIVYVOVVQLRL-UHFFFAOYSA-N 1,1-diethoxyethene Chemical compound CCOC(=C)OCC VTGIVYVOVVQLRL-UHFFFAOYSA-N 0.000 claims 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims 2
- IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 0.000 claims 2
- 239000000203 mixture Substances 0.000 claims 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- FJTRNRFAIZEJJJ-UHFFFAOYSA-N 1,1-dimethoxyethene Chemical compound COC(=C)OC FJTRNRFAIZEJJJ-UHFFFAOYSA-N 0.000 claims 1
- 125000003545 alkoxy group Chemical group 0.000 claims 1
- 239000011260 aqueous acid Substances 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- 150000004677 hydrates Chemical class 0.000 claims 1
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 claims 1
- WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 claims 1
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 claims 1
- RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 claims 1
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 claims 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims 1
- 239000002904 solvent Substances 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
-
- 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
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Cardiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Heart & Thoracic Surgery (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Claims (17)
1. Postupak za sintezu spoja formule (I): naznačen time, da je spoj formule (VII): izložen djelovanju 1-(izocijanometilsulfonil)-4-metilbenzena (TosMIC) u nazočnosti lužine u organskom otapalu kako bi se dobio spoj formule (I).
2. Postupak u skladu s patentnim zahtjevom 1, naznačen time, da je količina 1-(izocijano-metilsulfonil)-4-metilbenzena korištena za izvođenje pretvaranja spoja formule (VII) kako bi se dobio spoj formule (I) od 2 do 5 ekvivalenta.
3. Postupak u skladu s patentinm zahtjevom 1 ili s patentnim zahtjevom 2, naznačen time, da je lužina koja je korištena za pretvaranje spoja formule (VII) kako bi se dobio spoj formule (I), odabrana od kalij terc-butoksida, natrij terc-butoksida, kalij etoksida, natrij etoksida, kalij metoksida i natrij metoksida.
4. Postupak u skladu s patentnim zahtjevom 3, naznačen time, da lužina korištena za izvođenje pretvaranja spoja formule (VII) kako bi se dobio spoj formule (I) jeste kalij terc-butoksid.
5. Postupak u skladu s bilo kojim od patentnih zahtjeva 1 do 4, naznačen time, da organsko otapalo koje je korišteno za izvođenje pretvaranja spoja formule (VII) kako bi se dobio spoj formule (I) je odabrano od metanola, etanola, izopropanola, terc-butanola, tetrahidrofurana, etilen glikola i dimetil sulfoksida ili smjese od dva od navedenih otapala.
6. Postupak u skladu s patentnim zahtjevom 5, naznačen time, da organsko otapalo koje je korišteno za izvođenje pretvaranja spoja formule (VII) kako bi se dobio spoj formule (I) je smjesa tetrahidrofurana i metanola.
7. Postupak u skladu s bilo kojim od patentnih zahtjeva 1 do 6, naznačen time, da se pretvaranje spoja formule (VII) kako bi se dobio spoj formule (I) izvodi pri temperaturi od -20°C do 50°C.
8. Postupak u skladu s patentnim zahtjevom 1, naznačen time, da je spoj formula (VII) pripravljen počevši od spoja formule (VIII): koji spoj se pretvara u spoj formule (IX): gdje R predstavlja (C1-C4)alkilnu skupinu, u nazočnosti 1,1-dialkoksietena, alkoksi skupina koje imaju od 1 do 4 ugljikova atoma i organometalnog spoja u organskom otapalu, koji spoj formule (IX) je hidroliziran u organovodenom kiselom mediju kako bi se dobio spoj formule (VII):
9. Postupak u skladu s patentnim zahtjevom 8, naznačen time, da 1,1-dialkoksieten koji je korišten za izvođenje pretvaranja spoja formule (VIII) kako bi se dobio spoj formule (IX) je 1,1-dietoksieten.
10. Postupak u skladu s patentnim zahtjevom 9, naznačen time, da količina 1,1-dietoksietena koji je korišten za izvođenje pretvaranja spoja formule (VIII) kako bi se dobio spoj formule (IX) je od 0.8 do 5 ekvivalenta.
11. Postupak u skladu s bilo kojim od patentnih zahtjeva 8 do 10, naznačen time, da organometalni spoj, koji je korišten za izvođenje pretvaranja spoja formule (VIII) kako bi se dobio spoj formule (IX), je odabran od n-butilitija, s-butilitija, t-butilitija, fenilitija i izopropilmagnezij klorida.
12. Postupak u skladu s patentnim zahtjevom 11, naznačen time, da organometalni spoj, koji je korišten za izvođenje pretvaranja spoja formule (VIII) kako bi se dobio spoj formule (IX), je n-butilitij.
13. Postupak u skladu s patentnim zahtjevom 12, naznačen time, da količina n-butilitija, koja je korištena za izvođenje pretvaranja spoja formule (VIII) kako bi se dobio spoj formule (IX), je od 1 do 3 ekvivalenta.
14. Postupak u skladu s bilo kojim od patentnih zahtjeva 8 do 13, naznačen time, da organsko otapalo, koje je korišteno za izvođenje pretvaranja spoja formule (VIII) kako bi se dobio spoj formule (IX), je odabrano od toluena, tetrahidrofurana, diklorometana i klorobenzena.
15. Postupak u skladu s patentnim zahtjevom 14, naznačen time, da organsko otapalo, koje je korišteno za izvođenje pretvaranja spoja formule (VIII) kako bi se dobio spoj formule (I) je toluen.
16. Postupak u skladu s bilo kojim od patentnih zahtjeva 1 do 15, naznačen time, da se pretvaranje spoja formule (VIII) kako bi se dobio spoj formule (IX) izvodi pri temperaturi od -20°C do 30°C.
17. Postupak za sintezu ivabradina, od njegovih farmaceutsk prihvatljivih soli i hidrata, naznačen time, da se spoj formule (VII) pretvara u intermedijer formule (I) sukladno postupku iz patentnog zahtjeva 1, nakon čega se intermedijer formule (I) pretvara u ivabradin.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR1354504A FR3005658B1 (fr) | 2013-05-17 | 2013-05-17 | "procede de synthese du 3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-triene-7-carbonitrile, et application a la synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable" |
| EP14168559.4A EP2803659B1 (fr) | 2013-05-17 | 2014-05-16 | Procédé de synthèse du 3,4-diméthoxybicyclo[4.2.0]octa-1,3,5-triène-7-carbonitrile, et application à la synthèse de l'ivabradine et de ses sels d'addition à un acide pharmaceutiquement acceptable |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ME02636B true ME02636B (me) | 2017-06-20 |
Family
ID=48874340
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MEP-2017-64A ME02636B (me) | 2013-05-17 | 2014-05-16 | Postupak za sintezu 3,4-dimetoksibiciklo[4.2.0]okta-1,3,5-trien-7-karbonitrila i uporaba za sintezu ivabradina i njegovih adicijskih soli s farmaceutski prihvatljivom kiselinom |
Country Status (36)
| Country | Link |
|---|---|
| US (1) | US8859763B1 (me) |
| EP (1) | EP2803659B1 (me) |
| JP (1) | JP5916793B2 (me) |
| KR (1) | KR101625128B1 (me) |
| CN (1) | CN104163777B (me) |
| AR (1) | AR096324A1 (me) |
| AU (1) | AU2014202434B2 (me) |
| BR (1) | BR102014011633A2 (me) |
| CA (1) | CA2851960C (me) |
| CY (1) | CY1120482T1 (me) |
| DK (1) | DK2803659T3 (me) |
| EA (1) | EA026224B1 (me) |
| ES (1) | ES2621804T3 (me) |
| FR (1) | FR3005658B1 (me) |
| GE (1) | GEP20156416B (me) |
| HK (2) | HK1200028A1 (me) |
| HR (1) | HRP20170394T1 (me) |
| HU (1) | HUE031370T2 (me) |
| IN (1) | IN2014DE01203A (me) |
| JO (1) | JO3276B1 (me) |
| LT (1) | LT2803659T (me) |
| MD (1) | MD4443C1 (me) |
| ME (1) | ME02636B (me) |
| MX (1) | MX345278B (me) |
| NZ (1) | NZ624774A (me) |
| PL (1) | PL2803659T3 (me) |
| PT (1) | PT2803659T (me) |
| RS (1) | RS55917B1 (me) |
| SA (1) | SA114350532B1 (me) |
| SG (1) | SG10201402034PA (me) |
| SI (1) | SI2803659T1 (me) |
| TW (1) | TWI500596B (me) |
| UA (1) | UA116337C2 (me) |
| UY (1) | UY35561A (me) |
| WO (1) | WO2014184501A1 (me) |
| ZA (1) | ZA201403543B (me) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR3005658B1 (fr) * | 2013-05-17 | 2015-04-24 | Servier Lab | "procede de synthese du 3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-triene-7-carbonitrile, et application a la synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable" |
| EP3101010A1 (en) | 2015-06-03 | 2016-12-07 | Urquima S.A. | New method for the preparation of highly pure ivabradine base and salts thereof |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2681862B1 (fr) * | 1991-09-27 | 1993-11-12 | Adir Cie | Nouvelles (benzocycloalkyl)alkylamines, leur procede de preparation, et les compositions pharmaceutiques qui les contiennent. |
| 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 |
| FR2933975B1 (fr) * | 2008-07-17 | 2011-02-18 | Servier Lab | Nouveau procede de preparation de benzocyclobutenes fonctionnalises,et application a la synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable. |
| CN102884410B (zh) | 2010-05-06 | 2015-05-27 | 株式会社岛津制作所 | 材料试验机 |
| HUP1000245A2 (en) * | 2010-05-07 | 2011-11-28 | Richter Gedeon Nyrt | Industrial process for the production ivabradin salts |
| FR3005658B1 (fr) * | 2013-05-17 | 2015-04-24 | Servier Lab | "procede de synthese du 3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-triene-7-carbonitrile, et application a la synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable" |
-
2013
- 2013-05-17 FR FR1354504A patent/FR3005658B1/fr active Active
-
2014
- 2014-05-02 IN IN1203DE2014 patent/IN2014DE01203A/en unknown
- 2014-05-05 AU AU2014202434A patent/AU2014202434B2/en not_active Ceased
- 2014-05-05 CN CN201410185124.1A patent/CN104163777B/zh not_active Expired - Fee Related
- 2014-05-05 SG SG10201402034PA patent/SG10201402034PA/en unknown
- 2014-05-06 JO JOP/2014/0157A patent/JO3276B1/ar active
- 2014-05-08 MD MDA20140048A patent/MD4443C1/ro not_active IP Right Cessation
- 2014-05-09 NZ NZ624774A patent/NZ624774A/en not_active IP Right Cessation
- 2014-05-12 CA CA2851960A patent/CA2851960C/fr not_active Expired - Fee Related
- 2014-05-12 UY UY0001035561A patent/UY35561A/es not_active Application Discontinuation
- 2014-05-14 UA UAA201405094A patent/UA116337C2/uk unknown
- 2014-05-14 GE GEAP201413468A patent/GEP20156416B/en unknown
- 2014-05-14 US US14/277,151 patent/US8859763B1/en not_active Expired - Fee Related
- 2014-05-14 TW TW103117037A patent/TWI500596B/zh not_active IP Right Cessation
- 2014-05-14 BR BRBR102014011633-8A patent/BR102014011633A2/pt not_active IP Right Cessation
- 2014-05-14 MX MX2014005822A patent/MX345278B/es active IP Right Grant
- 2014-05-14 SA SA114350532A patent/SA114350532B1/ar unknown
- 2014-05-15 ZA ZA2014/03543A patent/ZA201403543B/en unknown
- 2014-05-16 EA EA201400473A patent/EA026224B1/ru not_active IP Right Cessation
- 2014-05-16 LT LTEP14168559.4T patent/LT2803659T/lt unknown
- 2014-05-16 PT PT141685594T patent/PT2803659T/pt unknown
- 2014-05-16 AR ARP140101965A patent/AR096324A1/es unknown
- 2014-05-16 ME MEP-2017-64A patent/ME02636B/me unknown
- 2014-05-16 HU HUE14168559A patent/HUE031370T2/hu unknown
- 2014-05-16 DK DK14168559.4T patent/DK2803659T3/da active
- 2014-05-16 JP JP2014101963A patent/JP5916793B2/ja active Active
- 2014-05-16 ES ES14168559.4T patent/ES2621804T3/es active Active
- 2014-05-16 SI SI201430179A patent/SI2803659T1/sl unknown
- 2014-05-16 EP EP14168559.4A patent/EP2803659B1/fr active Active
- 2014-05-16 WO PCT/FR2014/051140 patent/WO2014184501A1/fr active Application Filing
- 2014-05-16 KR KR1020140059053A patent/KR101625128B1/ko not_active IP Right Cessation
- 2014-05-16 RS RS20170308A patent/RS55917B1/sr unknown
- 2014-05-16 PL PL14168559T patent/PL2803659T3/pl unknown
- 2014-12-31 HK HK14113135.3A patent/HK1200028A1/zh not_active IP Right Cessation
-
2015
- 2015-01-14 HK HK15100395.4A patent/HK1199872A1/xx not_active IP Right Cessation
-
2017
- 2017-03-09 HR HRP20170394TT patent/HRP20170394T1/hr unknown
- 2017-04-03 CY CY20171100398T patent/CY1120482T1/el unknown
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