WO2009125430A3 - Improved process for producing darifenacin - Google Patents
Improved process for producing darifenacin Download PDFInfo
- Publication number
- WO2009125430A3 WO2009125430A3 PCT/IN2009/000160 IN2009000160W WO2009125430A3 WO 2009125430 A3 WO2009125430 A3 WO 2009125430A3 IN 2009000160 W IN2009000160 W IN 2009000160W WO 2009125430 A3 WO2009125430 A3 WO 2009125430A3
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- pyrrolidine
- diphenylmethyl
- give
- tosyl
- cyano
- Prior art date
Links
- HXGBXQDTNZMWGS-RUZDIDTESA-N darifenacin Chemical compound C=1C=CC=CC=1C([C@H]1CN(CCC=2C=C3CCOC3=CC=2)CC1)(C(=O)N)C1=CC=CC=C1 HXGBXQDTNZMWGS-RUZDIDTESA-N 0.000 title abstract 3
- 229960002677 darifenacin Drugs 0.000 title abstract 3
- 238000000034 method Methods 0.000 title abstract 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 abstract 10
- AQQVYYRHEMSRRM-QGZVFWFLSA-N 2,2-diphenyl-2-[(3s)-pyrrolidin-3-yl]acetonitrile Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C#N)[C@@H]1CCNC1 AQQVYYRHEMSRRM-QGZVFWFLSA-N 0.000 abstract 1
- NEBPTMCRLHKPOB-UHFFFAOYSA-N 2,2-diphenylacetonitrile Chemical compound C=1C=CC=CC=1C(C#N)C1=CC=CC=C1 NEBPTMCRLHKPOB-UHFFFAOYSA-N 0.000 abstract 1
- BCAYPPFBOJCRPN-UHFFFAOYSA-N 3-benzoylsulfanyl-2-methylpropanoic acid Chemical compound OC(=O)C(C)CSC(=O)C1=CC=CC=C1 BCAYPPFBOJCRPN-UHFFFAOYSA-N 0.000 abstract 1
- JRKZQRRYNCMSCB-UHFFFAOYSA-N 5-(2-bromoethyl)-2,3-dihydro-1-benzofuran Chemical compound BrCCC1=CC=C2OCCC2=C1 JRKZQRRYNCMSCB-UHFFFAOYSA-N 0.000 abstract 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 abstract 1
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 abstract 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 abstract 1
- 230000002378 acidificating effect Effects 0.000 abstract 1
- 230000015572 biosynthetic process Effects 0.000 abstract 1
- 230000000911 decarboxylating effect Effects 0.000 abstract 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 abstract 1
- 230000003301 hydrolyzing effect Effects 0.000 abstract 1
- 238000011065 in-situ storage Methods 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 239000002904 solvent Substances 0.000 abstract 1
- 238000007070 tosylation reaction Methods 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention discloses an improved process for producing darifenacin, the process comprising decarboxylating (2S,4R)-4-hydroxy-2-pyrrolidine carboxylic acid followed by in situ tosylation to give l-tosyl-3-(R)-(-)-hydroxypyrrolidine, tosylating the l-tosyl-3-(R)-(-)-hydroxypyrrolidine with methyl-p-toluenesuolphonate to give l-tosyl-3- (S)-(-)-tosyloxy pyrrolidine, reacting l-tosyl-3-(S)-(-)-tosyloxy pyrrolidine with diphenyl acetonitrile in presence of a base to give 3-(S)-(+)-(l-cyano-l,l-diphenylmethyl)-l- tosylpyrrolidine, de-protecting 3-(S)-(+)-(l-cyano-l,l-diphenylmethyl)-l- tosylpyrrolidine in the presence of phenol in acidic medium to give 3-(S)-(+)-(l-cyano- 1,1-diphenylmethyl) pyrrolidine, hydrolyzing 3-(S)-(+)-(l-cyano-l,l-diphenylmethyl) pyrrolidine followed by salt formation to obtain 3-(S)-(+)-(l-carbamoyl-l,l- diphenylmethyl)pyrrolidine.L-(+)-tartrate, condensing 3-(S)-(+)-( 1 -carbamoyl- 1,1- diphenylmethyl)pyrrolidine-L(+)-tartrate with 5-(2-bromoethyl)-2,3-dihydrobenzofuran employing a base in a solvent to give darifenacin.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN662/CHE/2008 | 2008-03-17 | ||
| IN662CH2008 | 2008-03-17 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| WO2009125430A2 WO2009125430A2 (en) | 2009-10-15 |
| WO2009125430A8 WO2009125430A8 (en) | 2010-01-21 |
| WO2009125430A3 true WO2009125430A3 (en) | 2010-04-22 |
Family
ID=41162347
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/IN2009/000160 WO2009125430A2 (en) | 2008-03-17 | 2009-03-09 | Improved process for producing darifenacin |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2009125430A2 (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5096890A (en) * | 1989-03-17 | 1992-03-17 | Pfizer Inc. | Pyrrolidine derivatives |
| WO2008029257A2 (en) * | 2006-09-07 | 2008-03-13 | Medichem, S.A. | Improved method for preparing 1,3-disubstituted pyrrolidine compounds |
-
2009
- 2009-03-09 WO PCT/IN2009/000160 patent/WO2009125430A2/en active Application Filing
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5096890A (en) * | 1989-03-17 | 1992-03-17 | Pfizer Inc. | Pyrrolidine derivatives |
| US5096890B1 (en) * | 1989-03-17 | 1995-03-28 | Pfizer | Pyrrolidine derivatives |
| WO2008029257A2 (en) * | 2006-09-07 | 2008-03-13 | Medichem, S.A. | Improved method for preparing 1,3-disubstituted pyrrolidine compounds |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2009125430A8 (en) | 2010-01-21 |
| WO2009125430A2 (en) | 2009-10-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| BRPI0618379A2 (en) | (3r, 5r) -7- [2- (4-fluorophenyl) -5-isopropyl-3-phenyl-4 - [(4-hydroxymethylphenylamino) carbonyl] -pyrroleic acid 1-yl] -3,5-dihydroxy heptanoic | |
| WO2007130453A3 (en) | Non-natural amino acid substituted polypeptides | |
| MA32297B1 (en) | Process for the preparation of 1- (2-halobiphenyl-4-yl) -cyclopropane carboxylic acid derivatives | |
| CY1116498T1 (en) | PROCEDURE FOR PREPARATION (R) - (-) - 3- (CARBAMOYLOMETHYL) -5-METHYLEXANIC ACID AND PREGAMPALIN AND INTERMEDIATE COMPOSITION | |
| EP2942954A3 (en) | Image decoding apparatus | |
| WO2007149371A3 (en) | Process for making isooctenes from dry isobutanol | |
| WO2009141362A3 (en) | Process for the stereoselective enzymatic hydrolysis of 5-methyl-3-nitromethyl-hexanoic acid ester | |
| EA201170181A1 (en) | POLYMORPHIC FORMS OF RAZAGILINA HYDROCHLORIDE | |
| ATE453622T1 (en) | METHOD FOR PRODUCING ENANTIOMERIC ENRICHED CYCLIC BETA-ARYL OR HETEROARYL CARBOXYLIC ACIDS | |
| WO2009001203A3 (en) | An improved process for the preparation of aprepitant | |
| SI2183201T1 (en) | Process for the resolution of zopiclone and intermediate compounds | |
| WO2009125430A8 (en) | Improved process for producing darifenacin | |
| WO2008126106A8 (en) | Novel and improved processes for the preparation of intermediates of darifenacin, darifenacin and its pharmaceutically acceptable salts | |
| LT2008068A (en) | Method for manufacture of escitalopram | |
| BRPI0821752A8 (en) | PROCESS FOR PREPARING 22-FLUORACYL-3-AMINO-ACRYLIC ACID DERIVATIVES | |
| WO2007052309A3 (en) | Improved process for manufacturing statins | |
| WO2011016052A3 (en) | Process for preparing pregabalin | |
| WO2009116081A3 (en) | An improved process for the preparation of aprepitant | |
| BR112012031597A2 (en) | processes for producing hexamethylenediamine (hmd), adiponitrile (adn), adipamide (adm) and derivatives thereof. | |
| WO2008104880A3 (en) | Stable solid dosage forms of an antidepressant | |
| JP2012510975A5 (en) | ||
| WO2008029257A3 (en) | Improved method for preparing 1,3-disubstituted pyrrolidine compounds | |
| BR0313246A (en) | Process for Preparation of 5- (4-Fluorphenyl) -1- [2 - ((2r, 4r) -4-hydroxy-6-oxo-tetrahydro-pyan-2-yl) ethyl] -2-isopropyl acid phenylamide -4-phenyl-1h-pyrrol-3-carbocyclic | |
| ZA200804664B (en) | Process for (3R, 5R)-7-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-[(4-hydroxy methyl phenyl amino) carbonyl]-pyrrol-1-yl]-3, 5-dihydroxy-heptanoic acid hemi calcium salt | |
| UA99640C2 (en) | Method for the preparation of darifenacin hydrogen bromide |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 09729301 Country of ref document: EP Kind code of ref document: A2 |
|
| NENP | Non-entry into the national phase |
Ref country code: DE |
|
| 122 | Ep: pct application non-entry in european phase |
Ref document number: 09729301 Country of ref document: EP Kind code of ref document: A2 |