133099-12-4Relevant articles and documents
Synthesis of Arylethylamines via C(sp3)-C(sp3) Palladium-Catalyzed Cross-Coupling
Lippa, Rhys A.,Battersby, David J.,Murphy, John A.,Barrett, Tim N.
, p. 3583 - 3604 (2021/02/27)
Substituted arylethylamines represent a key structural motif in natural, pharmaceutical, and agrochemical compounds. Access to such scaffolds has been the subject of long-standing synthetic interest. Herein, we report the synthesis of such scaffolds via a palladium-catalyzed C(sp3)-C(sp3) coupling between (chloromethyl)aryls and air-/moisture-stable N,N-dialkylaminomethyltrifluoroborate salts. Rapid hit identification was achieved using microscale high-throughput experimentation and was followed by millimolar-scale reaction parameter optimization. A range of structurally and electronically varied arylethylamine products were obtained in moderate to excellent yields (27-96%, >60 examples). The reaction mechanism is proposed to proceed via formation of a trialkylbenzylammonium species prior to oxidative addition.
A new solvent system (Cyclopentyl methyl ether-water) in process development of darifenacin HBr
Pramanik, Chinmoy,Bapat, Kiran,Chaudhari, Ashok,Tripathy, Narendra K.,Gurjar, Mukund K.
, p. 1591 - 1597 (2013/02/23)
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).
METHOD OF PRODUCING (S)-3-(1-CYANO-1,1-DIPHENYLMETHYL)-PYRROLIDINE
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Page/Page column 14, (2010/12/30)
The present application relates to a method of (S)-3-(1-cyano-1,1-diphenylmethyl)-pyrrolidine by reacting an (S)-1-protected-3-(sulfonyloxy)-pyrrolidine having an easily deprotectable protecting group with diphenylacetonitrile in the presence of a base to obtain an (S)-1-protected-3-(1-cyano-1,1-diphenylmethyl)-pyrrolidine and then deprotecting the obtained compound under a mild condition. According to the method of the present invention, it is possible to efficiently produce (S)-3-(1-cyano-1,1-diphenylmethyl)-pyrrolidine, which is an important intermediate in the process of producing a muscarinic receptor antagonist such as darifenacin.
PROCESS FOR PREPARATION OF DARIFENACIN AND INTERMEDIATES USED IN THE PROCESS
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Page/Page column 21-22, (2010/04/25)
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
SUBSTITUTED PYRROLIDINES
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Page/Page column 32, (2009/01/24)
Disclosed herein are substituted pyrrolidine-based muscarinic receptor modulators of Formula I, process of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.
PROCESS FOR PREPARING 3-SUBSTITUTED PYRROLIDINE COMPOUNDS
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Page/Page column 11; 12, (2010/01/12)
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.
NOVEL AND IMPROVED PROCESSES FOR THE PREPARATION OF INTERMEDIATES OF DARIFENACIN, DARIFENACIN AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS
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, (2008/12/08)
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.
PREPARATION OF DARIFENACIN AND ITS SALTS
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Page/Page column 15; 35-36, (2008/12/08)
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.
Quaternary ammonium diphenylmethyl compounds useful as muscarinic receptor antagonists
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Page/Page column 21, (2008/12/08)
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
SUBSTITUTED 4-AMINO-1-BENZYLPIPERIDINE COMPOUNDS
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Page 59, (2008/06/13)
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.
