- A new solvent system (Cyclopentyl methyl ether-water) in process development of darifenacin HBr
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Darifenacin is a potent and competitive M3 selective receptor antagonist (M3SRA), and its hydrobromide salt (1) is the active ingredient of pharmaceutical formulations for oral treatment of urinary incontinence. The present work demonstrates an efficient, commercial manufacturing process for darifenacin hydrobromide (1).
- Pramanik, Chinmoy,Bapat, Kiran,Chaudhari, Ashok,Tripathy, Narendra K.,Gurjar, Mukund K.
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p. 1591 - 1597
(2013/02/23)
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- PROCESS FOR PREPARATION OF DARIFENACIN AND INTERMEDIATES USED IN THE PROCESS
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Disclosed herein is a process for the preparation of darifenacin and physiologically acceptable salts thereof. Also disclosed is a compound of formula X: wherein R is linear or branched C 1-10 alkyl, phenyl, tolyl, ortho-, meta- or para- xylyl
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Page/Page column 23-24
(2010/04/25)
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- IMPROVED PROCESS FOR PRODUCING DARIFENACIN
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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.
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Page/Page column 7; 11
(2009/11/29)
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- PROCESS FOR PREPARING 3-SUBSTITUTED PYRROLIDINE COMPOUNDS
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Disclosed is a process for preparing 3 -substituted pyrrolidine compounds of formula (VII) or salts thereof, wherein R1 is described herein, which are intermediate compounds useful for the synthesis of darifenacin which is indicated for the treatment of overactive bladder with symptoms of urge, urinary incontinence, and the like, and pharmaceutically acceptable salts thereof. Also disclosed is a process for preparing darifenacin and pharmaceutically acceptable salts thereof.
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Page/Page column 12
(2010/01/12)
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- SUBSTITUTED PYRROLIDINES
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Disclosed herein are substituted pyrrolidine-based muscarinic receptor modulators of Formula I, process of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.
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Page/Page column 32; 33
(2009/01/24)
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- NOVEL AND IMPROVED PROCESSES FOR THE PREPARATION OF INTERMEDIATES OF DARIFENACIN, DARIFENACIN AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS
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The present invention relates to novel and improved processes for the preparation of intermediates of darifenacin, darifenacin and its pharmaceutically acceptable salts. Darifenacin is chemically known as 3 -(S)-(-)-(l -carbamoyl- 1,1 -diphenylmethyl)-l- [2- (2,3-dihydro benzofuran-5-yl)ethyl]pyrrolidine and represented by formula-2. The invention also relates to the novel polymorphs of the pharmaceutically acceptable salts of darifenacin and the methods for their re aration.
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- PREPARATION OF DARIFENACIN AND ITS SALTS
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Provided are various processes and compounds related to darifenacin and/or its salts. For example, there is provided a process for preparing a free base of darifenacin: Formula, or the salt thereof, the process including reacting 3-(S)-(cyanodiphenylmethyl)-1-[2-(2,3-dihydrobenzofuran-5-yl) ethyl] pyrrolidine of the Formula (IV), or a salt thereof: Formula (IV) with a base effective to convert the nitrile group of the compound of the Formula (IV) to the amide group of the darifenacin in an organic solvent, the reaction being carried out in the organic solvent, with a proviso that the solvent is not 2-methyl-butan-2-ol, and with further proviso that the reaction produces less than about 0.5 % of the compound of the Formula (Ic): Formula (Ic) in the reaction mass, as measured by HPLC. Various embodiments and variants are provided.
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Page/Page column 36-37
(2008/12/08)
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- Quaternary ammonium diphenylmethyl compounds useful as muscarinic receptor antagonists
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The invention provides compounds of formula I: in salt or zwitterionic form or a pharmaceutically acceptable salt thereof, wherein R1-6, a-e and Q are as defined in the specification. These compounds are muscarinic receptor antagonists. The inv
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Page/Page column 21
(2008/12/08)
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- PROCESSES FOR PREPARING DARIFENACIN HYDROBROMIDE
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The invention encompasses processes for the preparation of darifenacin hydrobromide.
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Page/Page column 42
(2008/06/13)
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- Crystalline form of a substituted pyrrolidine compound
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The invention provides a crystalline naphthalene-1,5-disulfonic acid salt of 2-[(S)-1-(8-methylaminooctyl)pyrrolidin-3-yl]-2,2-diphenylacetamide or a solvate thereof. This invention also provides pharmaceutical compositions comprising the salt or prepared
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Page/Page column 11
(2008/06/13)
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- SUBSTITUTED 4-AMINO-1-BENZYLPIPERIDINE COMPOUNDS
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This invention provides 4-amino-1-benzylpiperidine and related compounds and pharmaceutically acceptable salts thereof which are useful as muscarinic receptor antagonists. This invention also provides pharmaceutical compositions containing such compounds; processes and intermediates useful for preparing such compounds; and methods for treating disease conditions mediated by muscarinic receptors, such as overactive bladder, irritable bowel syndrome, asthma and chronic obstructive pulmonary disease, using such compounds.
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- Diphenylmethyl compounds useful as muscarinic receptor antagonists
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This invention provides compounds of formula I: wherein a, b, c, e, m, n, Ar1, R1, R2, R3, R4a, R4b, R5 and R6 are as defined in the specification. The compounds of fo
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Page/Page column 17-18
(2008/06/13)
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- NAPHTHALENE-1,5-DISULFONIC ACID SALTS OF A SUBSTITUTED 4-AMINO-1-(PYRIDYLMETHYL)PIPERIDINE COMPOUND
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This invention provides naphthalene-1,5-disulfonic acid salts of 4-{N-[7-(3-(S)-1-carbamoyl-1,1-diphenylmethyl)pyrrolidin-1-yl)hept-1-yl]-N-(isopropyl)amino}-1-(4-methoxypyrid-3-ylmethyl)piperidine, which salts are useful as muscarinic receptor antagonists. This invention is also directed to pharmaceutical compositions comprising these salt forms, methods of using these salt forms for treating medical conditions mediated by muscarinic receptors; and processes for preparing these salt forms.
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Page/Page column 24-25
(2010/02/11)
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- Diphenylmethyl compounds useful as muscarinic receptor antagonists
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This invention provides compounds of formula I: wherein a, b, c, e, m, R1, R2, R3, R4a, R4b, R5, R6, R7 and R8are as defined in the specification. The compo
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Page/Page column 17
(2010/02/14)
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- SUBSTITUTED 4-AMINO-1-(PYRIDYLMETHYL)PIPERIDINE AND RELATED COMPOUNDS
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This invention provides 4-amino-1-(pyridylmethyl)piperidine and related compounds and pharmaceutically acceptable salts thereof which are useful as muscarinic receptor antagonists. This invention also provides pharmaceutical compositions containing such compounds; processes and intermediates useful for preparing such compounds; and methods for treating disease conditions mediated by muscarinic receptors, such as overactive bladder, irritable bowel syndrome and chronic obstructive pulmonary disease, using such compounds.
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- DIARYLMETHYL AND RELATED COMPOUNDS
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This invention provides compounds of formula I: wherein R1, R2, R3, R4, R5, R6, R7, Ar1, Ar2, E, a, b, c, and z are as defined in the specification, or a pharmaceutically acceptable salt or solvate or stereoisomer thereof. The compounds of this invention possess both β2 adrenergic receptor agonist and muscarinic receptor antagonist activity. Such compounds are useful for treating pulmonary disorders, such as chronic obstructive pulmonary disease and asthma.
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- Substituted pyrrolidine and related compounds
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This invention is directed to compounds of formula I: wherein R1-R5 and a-e are as defined in the specification; or pharmaceutically-acceptable salt or solvate or stereoisomer thereof. The invention also directed to pharmaceutical co
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