EA201201525A1 - Промышленный способ синтеза солей ивабрадина - Google Patents
Промышленный способ синтеза солей ивабрадинаInfo
- Publication number
- EA201201525A1 EA201201525A1 EA201201525A EA201201525A EA201201525A1 EA 201201525 A1 EA201201525 A1 EA 201201525A1 EA 201201525 A EA201201525 A EA 201201525A EA 201201525 A EA201201525 A EA 201201525A EA 201201525 A1 EA201201525 A1 EA 201201525A1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- acid
- salts
- synthesis
- ivabradin
- hclo
- Prior art date
Links
- 230000015572 biosynthetic process Effects 0.000 title abstract 2
- 238000003786 synthesis reaction Methods 0.000 title abstract 2
- 238000004519 manufacturing process Methods 0.000 title 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 abstract 3
- ACRHBAYQBXXRTO-OAQYLSRUSA-N ivabradine Chemical class 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 abstract 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 abstract 2
- QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 abstract 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 abstract 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 abstract 2
- 150000003839 salts Chemical class 0.000 abstract 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 abstract 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 abstract 1
- 239000002253 acid Substances 0.000 abstract 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 abstract 1
- 229940071870 hydroiodic acid Drugs 0.000 abstract 1
- 239000000543 intermediate Substances 0.000 abstract 1
- 229960003825 ivabradine Drugs 0.000 abstract 1
- 238000000034 method Methods 0.000 abstract 1
- 229910017604 nitric acid Inorganic materials 0.000 abstract 1
- 235000006408 oxalic acid Nutrition 0.000 abstract 1
- 239000000126 substance Substances 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Saccharide Compounds (AREA)
Abstract
Способ синтеза солей ивабрадина формулы (I)химическое название которых соли 3-{3-[((S)-3,4-диметоксибицикло[4.2.0]окта-1,3,5-триен-7-илметил)метиламино]пропил}-7,8-диметокси-1,3,4,5-тетрагидро-2Н-3-бензазепин-2-она (HQ=HCl, HBr, HI, HNO, HClO, (СООН)), и новых промежуточных продуктов. Некоторые кристаллические формы кислотно-аддитивных солей ивабрадина (I) с азотной кислотой (I, НСQ=НNО), бромисто-водородной кислотой (I, HQ=HBr), иодисто-водородной кислотой (I, HQ=HI), щавелевой кислотой (I, HQ=(СООН)) и перхлорной кислотой (I, HQ=HClO).
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
HU1000245A HUP1000245A2 (en) | 2010-05-07 | 2010-05-07 | Industrial process for the production ivabradin salts |
PCT/HU2011/000044 WO2011138625A1 (en) | 2010-05-07 | 2011-05-06 | Industrial process for the synthesis of ivabradine salts |
Publications (2)
Publication Number | Publication Date |
---|---|
EA201201525A1 true EA201201525A1 (ru) | 2013-04-30 |
EA025533B1 EA025533B1 (ru) | 2017-01-30 |
Family
ID=89989713
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EA201201525A EA025533B1 (ru) | 2010-05-07 | 2011-05-06 | Промышленный способ синтеза солей ивабрадина |
Country Status (12)
Country | Link |
---|---|
EP (1) | EP2566850B1 (ru) |
DK (1) | DK2566850T3 (ru) |
EA (1) | EA025533B1 (ru) |
ES (1) | ES2675805T3 (ru) |
HR (1) | HRP20181066T1 (ru) |
HU (2) | HUP1000245A2 (ru) |
LT (1) | LT2566850T (ru) |
PL (1) | PL2566850T3 (ru) |
PT (1) | PT2566850T (ru) |
RS (1) | RS57382B1 (ru) |
SI (1) | SI2566850T1 (ru) |
WO (1) | WO2011138625A1 (ru) |
Families Citing this family (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2986804A1 (fr) * | 2012-02-09 | 2013-08-16 | Servier Lab | Procede de synthese enzymatique de l'acide (7s) 3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-triene 7-carboxylique ou de ses esters, et application a la synthese de l'ivabradine et de ses sels |
FR2988720B1 (fr) * | 2012-03-27 | 2014-03-14 | Servier Lab | Nouveau procede de synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable |
WO2013150544A2 (en) * | 2012-04-02 | 2013-10-10 | Hetero Research Foundation | Ivabradine hydrochloride solid dispersion |
FR2993561B1 (fr) * | 2012-07-17 | 2014-10-31 | Servier Lab | Procede de synthese enzymatique de la (7s)-1-(3,4-dimethoxy bicyclo[4.2.0]octa-1,3,5-triene 7-yl) n-methyl methanamine, et application a la synthese de l'ivabradine et de ses sels |
FR2996845A1 (fr) * | 2012-10-12 | 2014-04-18 | Servier Lab | Nouveau procede de synthese du 3-(2-bromo-4,5-dimethoxyphenyl)propanenitrile, et application a la synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable |
FR2997696B1 (fr) * | 2012-11-08 | 2014-12-05 | Servier Lab | Nouveau procede de synthese du (2e)-3-(3,4-dimethoxyphenyl)prop-2-enenitrile, et application a la synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable |
WO2014114341A1 (en) | 2013-01-24 | 2014-07-31 | Synthon Bv | Process for making ivabradine |
FR3002542B1 (fr) * | 2013-02-28 | 2016-01-22 | Servier Lab | Procede de synthese enzymatique de l'acide (7s) 3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-triene 7-carboxylique et application a la synthese de l'ivabradine et de ses sels |
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" |
ITMI20130830A1 (it) * | 2013-05-22 | 2014-11-23 | Laboratorio Chimico Int Spa | Procedimento per la preparazione di ivabradina |
EP3101010A1 (en) | 2015-06-03 | 2016-12-07 | Urquima S.A. | New method for the preparation of highly pure ivabradine base and salts thereof |
CN105669554A (zh) * | 2016-02-22 | 2016-06-15 | 徐建立 | 一种盐酸伊伐布雷定杂质及其制备方法和应用 |
CN107698508B (zh) * | 2017-10-24 | 2021-01-05 | 重庆东得医药科技有限公司 | 一种脱氢伊伐布雷定的合成方法 |
CN107698509B (zh) * | 2017-10-24 | 2020-04-21 | 重庆东得医药科技有限公司 | 一种脱氢伊伐布雷定草酸盐的制备方法 |
CN108947800B (zh) * | 2018-06-20 | 2021-07-27 | 安徽美诺华药物化学有限公司 | 一种(1s)-4,5-二甲氧基-1-(羰基氨基甲基)苯并环丁烷的合成方法 |
Family Cites Families (18)
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 |
US4618683A (en) | 1982-06-01 | 1986-10-21 | Abbott Laboratories | Tetrahydro-6,7-dimethoxy-1H-benz[e]isoinodolines useful in the treatment of hypertension and as sedatives |
FR2681862B1 (fr) | 1991-09-27 | 1993-11-12 | Adir Cie | Nouvelles (benzocycloalkyl)alkylamines, leur procede de preparation, et les compositions pharmaceutiques qui les contiennent. |
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 |
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 |
FR2882555B1 (fr) | 2005-02-28 | 2007-05-04 | Servier Lab | Forme cristalline gamma du chlorhydrate de l'ivabradine, son procede de preparation, et les compositions pharmaceutiques qui la contiennent |
FR2882554B1 (fr) | 2005-02-28 | 2007-05-04 | Servier Lab | Forme critalline beta d du chlorhydrate de l'ivabradine, son procede de preparation, et les compositions pharmaceutiques qui la contiennent |
FR2882553B1 (fr) | 2005-02-28 | 2007-05-04 | Servier Lab | Forme cristalline beta du chlorhydrate de l'ivabradine, son procede de preparation, et les compositions pharmaceutiques qui la contiennent |
FR2882556B1 (fr) | 2005-02-28 | 2007-05-04 | Servier Lab | Forme cristalline gamma d du chlorhydrate de l'ivabradine, son procede de preparation, et les compositions pharmaceutiques qui la contiennent |
FR2891826B1 (fr) | 2005-10-11 | 2007-12-28 | Servier Lab | Forme cristalline 6 du chlorhydrate de l'ivabradine, son procede de preparation et les compositions pharmaceutiques qui la contiennent |
FR2891827B1 (fr) | 2005-10-11 | 2007-12-28 | Servier Lab | Forme cristalline deltad du chlorhydrate de l'ivabradine, son procede de preparation, et les compositions pharmaceutiques qui la contiennent |
EP2097383B1 (en) | 2006-11-30 | 2012-02-08 | Cadila Healthcare Limited | Process for preparation of ivabradine hydrochloride |
JP5632279B2 (ja) * | 2007-05-30 | 2014-11-26 | アイエヌディー−スイフト ラボラトリーズ リミテッド | 塩酸イバブラジンの調製方法及びポリモルフ |
SI22750A (sl) | 2008-04-07 | 2009-10-31 | Krka D.D. | Ivabradin hidrobromid |
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 |
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. |
FR2935381B1 (fr) * | 2008-08-29 | 2010-12-17 | Servier Lab | Nouveau procede de resolution des enantiomerees du (3,4-dimethoxy-bicyclo°4.2.0!octa-1,3,5-trien-7-yl)nitrile et application a la synthese de l'ivabradine |
CN101671265B (zh) * | 2008-09-12 | 2012-08-15 | 中国科学院上海药物研究所 | 一种苯并环丁烷类化合物及其制备方法与用途 |
-
2010
- 2010-05-07 HU HU1000245A patent/HUP1000245A2/hu unknown
-
2011
- 2011-05-06 WO PCT/HU2011/000044 patent/WO2011138625A1/en active Application Filing
- 2011-05-06 PT PT117247338T patent/PT2566850T/pt unknown
- 2011-05-06 EP EP11724733.8A patent/EP2566850B1/en active Active
- 2011-05-06 RS RS20180753A patent/RS57382B1/sr unknown
- 2011-05-06 PL PL11724733T patent/PL2566850T3/pl unknown
- 2011-05-06 ES ES11724733.8T patent/ES2675805T3/es active Active
- 2011-05-06 LT LTEP11724733.8T patent/LT2566850T/lt unknown
- 2011-05-06 SI SI201131512T patent/SI2566850T1/en unknown
- 2011-05-06 DK DK11724733.8T patent/DK2566850T3/en active
- 2011-05-06 HU HUE11724733A patent/HUE037935T2/hu unknown
- 2011-05-06 EA EA201201525A patent/EA025533B1/ru unknown
-
2018
- 2018-07-10 HR HRP20181066TT patent/HRP20181066T1/hr unknown
Also Published As
Publication number | Publication date |
---|---|
PT2566850T (pt) | 2018-07-12 |
ES2675805T3 (es) | 2018-07-12 |
HRP20181066T1 (hr) | 2018-09-07 |
HU1000245D0 (en) | 2010-06-28 |
HUE037935T2 (hu) | 2018-09-28 |
LT2566850T (lt) | 2018-07-25 |
WO2011138625A1 (en) | 2011-11-10 |
SI2566850T1 (en) | 2018-08-31 |
EP2566850A1 (en) | 2013-03-13 |
PL2566850T3 (pl) | 2018-09-28 |
EA025533B1 (ru) | 2017-01-30 |
HUP1000245A2 (en) | 2011-11-28 |
EP2566850B1 (en) | 2018-04-11 |
RS57382B1 (sr) | 2018-09-28 |
DK2566850T3 (en) | 2018-07-23 |
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