JP2012197282A5 - - Google Patents
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- Publication number
- JP2012197282A5 JP2012197282A5 JP2012115710A JP2012115710A JP2012197282A5 JP 2012197282 A5 JP2012197282 A5 JP 2012197282A5 JP 2012115710 A JP2012115710 A JP 2012115710A JP 2012115710 A JP2012115710 A JP 2012115710A JP 2012197282 A5 JP2012197282 A5 JP 2012197282A5
- Authority
- JP
- Japan
- Prior art keywords
- organic solvent
- formula
- acid
- mixture
- salt
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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- SYHWYWHVEQQDMO-UHFFFAOYSA-N methyl 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound C=1C=CSC=1C(O)(C(=O)OC)C1=CC=CS1 SYHWYWHVEQQDMO-UHFFFAOYSA-N 0.000 claims description 7
- FIMXSEMBHGTNKT-UHFFFAOYSA-N Scopine Natural products CN1C2CC(O)CC1C1C2O1 FIMXSEMBHGTNKT-UHFFFAOYSA-N 0.000 claims description 4
- 238000000034 method Methods 0.000 claims 26
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims 15
- 150000007529 inorganic bases Chemical class 0.000 claims 11
- 239000000203 mixture Substances 0.000 claims 11
- FIMXSEMBHGTNKT-RZVDLVGDSA-N scopine Chemical class C([C@@H]1N2C)[C@H](O)C[C@@H]2[C@@H]2[C@H]1O2 FIMXSEMBHGTNKT-RZVDLVGDSA-N 0.000 claims 11
- 239000003495 polar organic solvent Substances 0.000 claims 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims 6
- 229910017053 inorganic salt Inorganic materials 0.000 claims 5
- 239000003960 organic solvent Substances 0.000 claims 5
- LERNTVKEWCAPOY-VOGVJGKGSA-N C[N+]1(C)[C@H]2C[C@H](C[C@@H]1[C@H]1O[C@@H]21)OC(=O)C(O)(c1cccs1)c1cccs1 Chemical compound C[N+]1(C)[C@H]2C[C@H](C[C@@H]1[C@H]1O[C@@H]21)OC(=O)C(O)(c1cccs1)c1cccs1 LERNTVKEWCAPOY-VOGVJGKGSA-N 0.000 claims 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims 4
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 claims 4
- 239000000706 filtrate Substances 0.000 claims 4
- 150000002825 nitriles Chemical class 0.000 claims 4
- VPJFFOQGKSJBAY-UHFFFAOYSA-N scopine di(2-thienyl) glycolate Chemical compound C1C(C2C3O2)N(C)C3CC1OC(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 VPJFFOQGKSJBAY-UHFFFAOYSA-N 0.000 claims 4
- 229960000257 tiotropium bromide Drugs 0.000 claims 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims 3
- 239000000725 suspension Substances 0.000 claims 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims 2
- 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 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims 2
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims 2
- 239000004327 boric acid Substances 0.000 claims 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 claims 2
- 150000004292 cyclic ethers Chemical class 0.000 claims 2
- 238000001914 filtration Methods 0.000 claims 2
- 239000001530 fumaric acid Substances 0.000 claims 2
- 238000010438 heat treatment Methods 0.000 claims 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims 2
- 239000011976 maleic acid Substances 0.000 claims 2
- 229940102396 methyl bromide Drugs 0.000 claims 2
- 238000002360 preparation method Methods 0.000 claims 2
- 239000007787 solid Substances 0.000 claims 2
- IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical compound NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 claims 2
- 239000011975 tartaric acid Substances 0.000 claims 2
- 235000002906 tartaric acid Nutrition 0.000 claims 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims 2
- 238000005406 washing Methods 0.000 claims 2
- 239000002253 acid Substances 0.000 claims 1
- 238000005273 aeration Methods 0.000 claims 1
- 150000002576 ketones Chemical class 0.000 claims 1
- 229910052757 nitrogen Inorganic materials 0.000 claims 1
- 239000011541 reaction mixture Substances 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 1
- 0 *C(C(c1ccc[s]1)(c1ccc[s]1)O)=O Chemical compound *C(C(c1ccc[s]1)(c1ccc[s]1)O)=O 0.000 description 1
- TUSYXLWQAHTQFG-UHFFFAOYSA-N CN(C(C1)CC(C2)OC(C(c3ccc[s]3)(c3ccc[s]3)O)=O)C2C1[O-] Chemical compound CN(C(C1)CC(C2)OC(C(c3ccc[s]3)(c3ccc[s]3)O)=O)C2C1[O-] TUSYXLWQAHTQFG-UHFFFAOYSA-N 0.000 description 1
- MEBLMEQTTYOXIT-UHFFFAOYSA-N COC(C(C1SC=CC1)(c1ccc[s]1)O)=O Chemical compound COC(C(C1SC=CC1)(c1ccc[s]1)O)=O MEBLMEQTTYOXIT-UHFFFAOYSA-N 0.000 description 1
Applications Claiming Priority (10)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US83023106P | 2006-07-10 | 2006-07-10 | |
| US60/830,231 | 2006-07-10 | ||
| US83520106P | 2006-08-03 | 2006-08-03 | |
| US83520006P | 2006-08-03 | 2006-08-03 | |
| US60/835,200 | 2006-08-03 | ||
| US60/835,201 | 2006-08-03 | ||
| US83603706P | 2006-08-07 | 2006-08-07 | |
| US60/836,037 | 2006-08-07 | ||
| US11/643,013 US20070167480A1 (en) | 2005-12-19 | 2006-12-19 | Pure and stable tiotropium bromide |
| US11/643,013 | 2006-12-19 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007181381A Division JP5048408B2 (ja) | 2006-07-10 | 2007-07-10 | 臭化チオトロピウムの調製方法 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2012197282A JP2012197282A (ja) | 2012-10-18 |
| JP2012197282A5 true JP2012197282A5 (cg-RX-API-DMAC7.html) | 2012-11-29 |
| JP5155472B2 JP5155472B2 (ja) | 2013-03-06 |
Family
ID=38814323
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007181381A Active JP5048408B2 (ja) | 2006-07-10 | 2007-07-10 | 臭化チオトロピウムの調製方法 |
| JP2012115710A Active JP5155472B2 (ja) | 2006-07-10 | 2012-05-21 | 臭化チオトロピウムの調製方法 |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007181381A Active JP5048408B2 (ja) | 2006-07-10 | 2007-07-10 | 臭化チオトロピウムの調製方法 |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US20070167480A1 (cg-RX-API-DMAC7.html) |
| EP (1) | EP2018379B1 (cg-RX-API-DMAC7.html) |
| JP (2) | JP5048408B2 (cg-RX-API-DMAC7.html) |
| AT (1) | ATE554086T1 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2658165A1 (cg-RX-API-DMAC7.html) |
| ES (1) | ES2384652T3 (cg-RX-API-DMAC7.html) |
| PL (1) | PL2018379T3 (cg-RX-API-DMAC7.html) |
| TW (1) | TW200813046A (cg-RX-API-DMAC7.html) |
| WO (1) | WO2008008376A2 (cg-RX-API-DMAC7.html) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20080039974A (ko) * | 2005-08-06 | 2008-05-07 | 베링거 인겔하임 인터내셔날 게엠베하 | 중증 지속성 천식의 치료에서 티오트로퓸 염의 용도 |
| EP1971332B1 (en) * | 2006-01-04 | 2011-03-09 | Boehringer Ingelheim International GmbH | Use of tiotropium salts in the treatment of moderate persistent asthma |
| PT2240477E (pt) * | 2008-01-10 | 2014-11-19 | Generics Uk Ltd | Um novo processo para a preparação de ésteres de escopina |
| WO2010075090A2 (en) * | 2008-12-15 | 2010-07-01 | Auspex Pharmaceuticals, Inc. | Scopine modulators of muscarinic acetylcholine receptor |
| WO2010084924A1 (ja) | 2009-01-26 | 2010-07-29 | 旭硝子株式会社 | 電子デバイス用基板の製造方法、電子デバイスの製造方法、電子デバイス用基板、および電子デバイス |
| WO2011015883A1 (en) * | 2009-08-07 | 2011-02-10 | Generics [Uk] Limited | Dichloromethane solvate of tiotropium bromide and its use |
| US8697719B2 (en) * | 2009-08-07 | 2014-04-15 | Generics [Uk] Limited | Anhydrate of tiotropium bromide |
| WO2011095800A2 (en) * | 2010-02-02 | 2011-08-11 | Generics [Uk] Limited | Analytical methods |
| TR201102068A2 (tr) * | 2011-03-03 | 2012-09-21 | Bi̇lgi̇ç Mahmut | Tiotropyum bromür içeren kristal maddeler |
| CZ304368B6 (cs) * | 2011-11-28 | 2014-04-02 | Zentiva, K.S. | Směsný solvát tiotropium bromidu a způsob jeho přípravy |
| PT106142B (pt) * | 2012-02-10 | 2014-07-18 | Hovione Farmaci Ncia S A | Processo para a preparação de brometo de tiotrópio |
| CZ304808B6 (cs) | 2012-03-16 | 2014-11-05 | Zentiva, K.S. | Způsob přípravy skopinesteru kyseliny di(2-thienyl)glykolové, intermediátu v syntéze tiotropium bromidu a jeho nová forma |
| CZ305012B6 (cs) | 2012-03-30 | 2015-03-25 | Zentiva, K.S. | Způsob přípravy skopinesteru kyseliny di(2-thienyl)glykolové, intermediátu v syntéze tiotropium bromidu |
| CN106188012B (zh) * | 2014-06-20 | 2018-11-30 | 深圳信立泰药业股份有限公司 | 一种阿利沙坦酯结晶及其制备方法及含有该结晶的药物组合物 |
| WO2019129801A1 (en) | 2017-12-28 | 2019-07-04 | Linnea S.A. | Process for the purification of methyl-2,2-dithienylglycolate |
| WO2021133280A1 (en) * | 2019-12-27 | 2021-07-01 | Deva Holding | An improved process for preparation of scopine hydrobromide |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1469781A (en) * | 1974-06-10 | 1977-04-06 | Boehringer Sohn Ingelheim | Production of scopine |
| DE3211185A1 (de) * | 1982-03-26 | 1983-09-29 | Boehringer Ingelheim KG, 6507 Ingelheim | Neue quartaere 6,11-dihydro-dibenzo-(b,e)-thiepin-11-n-alkyl- norscopinether und verfahren zu deren herstellung |
| US5610163A (en) * | 1989-09-16 | 1997-03-11 | Boehringer Ingelheim Gmbh | Esters of thienyl carboxylic acids and amino alcohols and their quaternization products |
| DE3931041C2 (de) * | 1989-09-16 | 2000-04-06 | Boehringer Ingelheim Kg | Ester von Thienylcarbonsäuren mit Aminoalkoholen, ihre Quaternierungsprodukte, Verfahren zu ihrer Herstellung und diese enthaltende Arzneimittel |
| MXPA02005666A (es) * | 2000-10-12 | 2002-11-29 | Boehringer Ingelheim Pharma | Nuevos polvos para anhalacion que contienen tiotropio. |
| US6908928B2 (en) * | 2000-10-12 | 2005-06-21 | Bi Pharma Kg. | Crystalline tiotropium bromide monohydrate, processes for the preparation thereof, and pharmaceutical compositions |
| DE10050995A1 (de) * | 2000-10-14 | 2002-04-18 | Boehringer Ingelheim Pharma | Neue Anticholinergika, Verfahren zu deren Herstellung und deren Verwendung als Arzneimittel |
| DE10064816A1 (de) * | 2000-12-22 | 2002-06-27 | Boehringer Ingelheim Pharma | Verfahren zur Herstellung eines Anticholinergikums |
| US6608055B2 (en) * | 2001-06-22 | 2003-08-19 | Boehringer Ingelheim Pharma Kg | Crystalline anticholinergic, processes for preparing it and its use for preparing a pharmaceutical composition |
| DE602004021921D1 (de) * | 2003-05-28 | 2009-08-20 | Theravance Inc | Azabicycloalkanverbindungen als muscarinrezeptor antagonisten |
| EP2322522A1 (de) * | 2003-11-03 | 2011-05-18 | Boehringer Ingelheim International Gmbh | Neue Tiotropiumsalze, Verfahren zu deren Herstellung sowie diese enthaltende Arzneimittelformulierungen |
| EP1879888A2 (en) * | 2005-05-02 | 2008-01-23 | Boehringer Ingelheim International GmbH | Crystalline forms of tiotropium bromide |
-
2006
- 2006-12-19 US US11/643,013 patent/US20070167480A1/en not_active Abandoned
-
2007
- 2007-07-10 EP EP07810332A patent/EP2018379B1/en active Active
- 2007-07-10 ES ES07810332T patent/ES2384652T3/es active Active
- 2007-07-10 TW TW096125102A patent/TW200813046A/zh unknown
- 2007-07-10 PL PL07810332T patent/PL2018379T3/pl unknown
- 2007-07-10 JP JP2007181381A patent/JP5048408B2/ja active Active
- 2007-07-10 AT AT07810332T patent/ATE554086T1/de active
- 2007-07-10 WO PCT/US2007/015787 patent/WO2008008376A2/en not_active Ceased
- 2007-07-10 CA CA002658165A patent/CA2658165A1/en not_active Abandoned
-
2012
- 2012-05-21 JP JP2012115710A patent/JP5155472B2/ja active Active