133099-04-4Relevant 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).
Novel Polymorphs of Darifenacin Free Base and its Hydrobromide Salt
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Page/Page column 7, (2010/08/18)
The present invention provides a novel and stable amorphous form of darifenacin free base, process for preparation, pharmaceutical compositions, and method of treating thereof. The present invention further provides a novel and stable polymorphic form of darifenacin hydrobromide, process for preparation, pharmaceutical compositions, and method of treating thereof.
IMPROVED PROCESS FOR PRODUCING DARIFENACIN
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, (2009/11/29)
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.
NOVEL PROCESS FOR THE PREPARATION OF (3SM-[2-(2 J-DIHYDRO-5- BENZOFURANYL?ETHYL]-α.α -DIPHENYL-3-PYRROLIDINEACETAMIDE HYDROBROMIDE
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, (2009/11/29)
The present invention is directed to a novel, industrially viable and cost effective process for manufacturing (3 S)- 1 -[2-(2,3-Dihydro-5-benzofuranyl)ethyl]-a,a-diphenyl-3-pyrrolidineacetamide hydrobromide also known as Darifenacin hydrobromide.
SUBSTITUTED PYRROLIDINES
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Page/Page column 33, (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.
A METHOD FOR THE PREPARATION OF DARIFENACIN HYDROGEN BROMIDE
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Page/Page column 9, (2009/09/05)
A method of preparing (3S)-l-[2-(2,3-dihydro-5-benzofuranyl)ethyl}-α,α-diphenyl-3- pyrrolidine acetamide hydrogen bromide, wherein 3-(S)-(I -carbamoyl- 1,1- diphenylmethyl)pyrrolidine or its salt with an organic acid is alkylated in the presence of an ino
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 43, (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.
PROCESSES FOR PREPARING DARIFENACIN HYDROBROMIDE
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Page/Page column 50, (2008/06/13)
The invention encompasses processes for the preparation of darifenacin hydrobromide.
