- Darifenacin intermediate 2, 3 - dihydro - 5 - benzofuran acetic acid preparation new method of (by machine translation)
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The invention relates to a darifenacin intermediate - 2, 3 - dihydro - 5 - benzofuran acetic acid. By the P-hydroxy-acetic acid and bromo acetaldehyde acetal as the starting material, the presence of O - alkylation reaction under a condition of the corresponding ether compound; then by esterification reaction to obtain the corresponding ester; in PPA (poly phosphoric acid) under the action of the, cyclization to obtain 2, 3 - benzofuran - 5 - acetate; 2, 3 - benzofuran - 5 - acetic acid layer which hydrolysis, to acidify the corresponding carboxylic acid; obtained by catalytic hydrogenation of 2, 3 - dihydro - 5 - benzofuran acetic acid; or the first 2, 3 - benzofuran - 5 - acetate obtained by catalytic hydrogenation of 2, 3 - dihydro - 5 - benzofuran acetic acid esters; and hydrolyzed, acidified to obtain 2, 3 - dihydro - 5 - benzofuran acetic acid. The method of the invention by simple and safe, each reaction raw materials are cheap and easy to obtain, the reaction yield is high, and is particularly suitable for industrial production of 2, 3 - dihydro - 5 - benzofuran acetic acid. (by machine translation)
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Paragraph 0067; 0068; 0069; 0070
(2018/04/03)
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- Novel preparation method of darifenacin intermediate 2,3-dihydro-5-benzofuran acetic acid
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The invention relates to a novel preparation method of a darifenacin intermediate 2,3-dihydro-5-benzofuran acetic acid. The method comprises the following steps: by taking 2,3-dihydrobenzofuran as aninitial raw material in the presence of a Lewis acid, carrying out a Friedel-Crafts acylation reaction with ethyl oxalyl monochloride so as to obtain a corresponding acyl compound; hydrolyzing to obtain alpha-ketonic acid sodium salt; reducing carbonyl into methylene by utilizing a Wolff-Kishner-HuangMinlong reaction, and acidizing, thereby obtaining the 2,3-dihydro-5-benzofuran acetic acid. The method disclosed by the invention is simple, convenient and safe, cheap and readily available in reactive raw materials and high in reaction yield and is particularly suitable for industrialized production of the 2,3-dihydro-5-benzofuran acetic acid.
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Paragraph 0054; 0055; 0056
(2018/04/03)
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- 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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- AN IMPROVED PROCESS FOR THE PREPARATION OF DARIFENACIN HYDROBROMIDE
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The present invention relates to an improved process for the preparation of Darifenacin hydrobromide of Formula (I). (i) condensing 3-(S)-(-)-1l-carbamoyl-1,1-diphenylmethyl)pyrrolidine (III), or its salt, with a compound of Formula XIII in the presence of a. base in a solvent, wherein X represents Cl, Br, C1-3 alkyl sulfonate or C6-10 arγl sulfonate; to produce (S)-2-[1-[2-(2,3-dihydrobenzofuran-5-yl)ethyl]-3- pyrrolidinyl]-2,2-diphenylacetamide (Darifenacin) (Ia), (ix) treating (S)-2-[1-[2-(2,3-dihydrobenzofuran-5-yl)ethyl]-3-pyrrolidinyl]- 2,2-diphenylacetamide (Darifenacin) (Ia) with an acid in a solvent and water mixture, (x) isolating pure (S)-2-[1-[2-(2,3-dihydrobenzofuran-5-yl)ethyl]-3- pyrrolidinyl]-2,2-diphenylacetamide (Darifenacin) (Ia), (xi) treating pure Darifenacin (Ia) with HBr to produce Darifenacin hydrobromide (I).
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Page/Page column 12
(2011/06/26)
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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
(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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- OXAZOLE AND THIAZOLE DERIVATIVES AND THEIR USES
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A quaternary ammonium compound of formula (I) having M3 receptor antagonist activity; a composition comprising such a compound; the use of such a compound in therapy (such as asthma or COPD); and a method of treating a patient with such a compound.
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Page/Page column 29
(2008/12/08)
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- HIV-1 VIRION MATURATION INHIBITORS, COMPOSITIONS AND TREATMENTS USING THE SAME
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The present invention provides compounds of Formula I, II, III or IV, or pharmaceutically acceptable salts and solvates thereof, which are useful as inhibitors of human immunodeficiency virus (HIV) and are also useful for the treatment of HIV infections in HIV- infected mammals, including humans. The present invention also provides pharmaceutical compositions comprising compounds of Formula I1 II, III or IV, and their pharmaceutically acceptable salts and solvates.
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Page/Page column 30-31
(2008/06/13)
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- MUSCARINIC RECEPTOR ANTAGONISTS
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The invetion is a method of treating irritable bowel syndrome with a compound selected from the formula STR1 wherein R, R 1, m, n p are as defined in the specification, or a pharmaceutically acceptable salt thereof.
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- ANTICHOLINERGIC AGENTS
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Selective muscarinic receptor antagonists of formula (I): STR1 wherein R 1 and R 2 are both optionally substituted phenyl, the broken line is an optional bond, X is > COH--, > SiOH--or CH--when the double bond is absent or is > C= when the double bond is present, X being attached to a carbon atom of A, A is selected from certain piperidine and pyrrolidine groups, n is 1 to 3 and R 3 is optionally substituted phenyl or thienyl, pyridyl or pyrazinyl.
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- Certain 1-azabicyclo[2.2.1]heptanes useful as muscarinic receptor antagonists
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MUSCARINIC RECEPTOR ANTAGONISTS OF THE FOLLOWING FORMULAE: STR1 Muscarinic receptor antagonists, useful especially in the treatment of irritable bowel syndrome, of formula (IA) or (IB) or a pharmaceutically acceptable salt thereof, where R 2 and R 3 are each independently H, halo or C 1 -C 4 alkyl; m is 0, 1 or 2; n is 1, 2 or 3; Y is a direct link, O or S; with the proviso that when n is 1, Y is a direct link; Het is a group of formula (A) or (B), where p is 0, 1 or 2, q is 1, 2 or 3, and r is 0, 1, 2 or 3, with the proviso that the sum of p, q and r is at least 3, the N atom of ""Het"" being attached to the group (CH 2) n in formula (IA) and to the H atom in formula (IB); and R 1 is a group of formula (a), (b) or Het 1, where R 4 and R 5 are each independently H, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, --(CH 2) t OH, halo, trifluoromethyl, cyano, --(CH 2) t NR 6 R 7, --CO(C 1 -C 4 alkyl), --OCO(C 1 -C 4 alkyl), CH(OH)(C 1 -C 4 alkyl), --C(OH)(C 1 -C 4 alkyl) 2, --SO 2 NH 2, --(CH 2) t CONR 6 R 7 or --(CH 2) t COO(C 1 -C 4 alkyl); R 6 and R 7 are each independently H or C 1 -C 4 alkyl; t is 0, 1 or 2; X and X 1 are each independently O or CH 2 ; s is 1, 2 or 3; and Het 1 is pyridyl, pyrazinyl or thienyl.
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- Muscarinic receptor antagonists
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Compounds of the formula STR1 and the pharmaceutically acceptable salts thereof, wherein: Y is a direct link, --CH 2 --, --(CH 2) 2 --, --CH 2 O-- or --CH 2 S--; R is --CN or --CONH 2 ; and R 1 is STR2 where X and X 1 are each independently O or CH 2 ; and m is 1, 2 or 3, are muscarinic receptor antagonists useful in the treatment of diseases and conditions associated with the altered motility and/or tone of smooth muscle, such as irritable bowel syndrome.
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- MUSCARINIC RECEPTOR ANTAGONISTS
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A series of novel 3-phenyl-3-[1-(cyclicalkyl)pyrrolidin-3-yl] glutarimide derivatives have been prepared, including their pharmaceutically acceptable salts. The cyclic moiety present in these compounds is derived from either benzene or a heteroaryl such as benzofuran or 2,3-dihydrobenzofuran, or it is derived from an aromatic heterocyclic such as pyridine, pyrazine or thiophene, and it is attached to the adjacent alkyl group of the molecule by means of one of the available ring carbon atoms situated in the aromatic ring of the aforementioned cyclic ring moiety. These particular compounds are useful in therapy as selective muscarinic receptor antagonists, which are selective for smooth muscle muscarinic sites over cardiac muscarinic sites and therefore, are of value in the treatment of diseases associated with altered motility and/or smooth muscle tone as found in the gut, trachea and bladder. Methods for preparing these compounds from known starting materials are provided.
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- Certain amines which are muscarinic receptor antagonists
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Amines of the following formula: STR1 where the variables are defined in the specification are useful in the treatment of diseases associated with altered motility and/or tone of smooth muscle.
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- Muscarinic receptor antagonists
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Compounds of the formula I STR1 wherein X, Y and v are as defined below, novel intermediates used in their synthesis, and the pharmaceutically acceptable salts of such compounds and intermediates. The compounds of formula I and the novel intermediates used in their synthesis are muscarinic receptor antagonists that are selected for smooth muscle muscarinic sites and are useful in the prevention and treatment of diseases associated with altered motility or tone of smooth muscle, such as irritable bowel syndrome, diverticular disease, urinary incontinence, aesophageal achalasia, and chronic obstructive airways disease.
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- 1-ARYLETHYL-3-SUBSTITUTED PIPERIDINES
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A series of novel 1-(phenethyl) and 1-(1-heteroarylethyl)-3-substituted piperidine derivatives have been prepared, including their pharmaceutically acceptable salts and various novel key intermediates therefor. The 3-substituent present in these compounds is an unsubstituted or substituted diphenylmethoxy group or a diphenylmethoxy-derived group, while the 1-substituent is unsubstituted or substituted phenethyl or 1-(2-heteroarylethyl) wherein the heteroaryl moiety is thienyl, pyridyl or pyrazinyl. These compounds in the form of both their racemates and 3R-isomers, are useful in therapy as smooth muscle muscarinic receptor antagonists and therefore, are of value in the treatment diseases associated with altered motility and/or smooth muscle tone. The most preferred compound is (3R)-diphenylmethoxy-1-(3,4-methylenedioxyphenethyl)piperidine. Methods for preparing these compounds from known starting materials are provided.
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- PYRROLIDINE DERIVATIVES
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Compounds of the formula STR1 wherein R, Y and R 1 are as defined in the specification. These compounds are muscarinic receptor antagonists which are selective for smooth muscle muscarinic sites over cardiac muscarinic sites, and are useful in the treatment of diseases associated with altered motility on tone of smooth muscle, including irritable bowel syndrome, diverticular disease, urinary incontinence, oesophageal achalasia and chronic obstructive airways disease.
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- Muscarinic receptor antagonists
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A compound of the formula (IA) or (IB), useful in treating diseases associated with the altered motility and/or tone of smooth muscle, such as irritable bowel syndrome, of the formula:- and their pharmaceutically-acceptable salts, where Y is-CH?CH?-,-CH=CH-,-CH?-S-,-CH?-O-,-O-or-S-; and X is a group of the formula:- wherein m is 1 or 2; R1 and R2 are each independently H or C?-C? alkyl or together represent-(CH?)n-where n is an integer of from 2 to 5; R3 is H or C?-C? alkyl; Z is a direct link,-CH?-,-(CH? )?-,-CH?O-or-CH?S-; and R? is pyridyl, pyrazinyl, thienyl or a group of the formula:- where either R? and R? are each independently selected from H, C?-C? alkyl, C?-C? alkoxy, halo,-CF?,-CN,-(CH?) pNR? R?,-OCO(C?-C? alkyl),-CO(C?-C? alkyl),-CH(OH)(C?-C? alkyl),-C(OH) (C?-C? alkyl)?,-SO?NH?,-NHSO?(C?-C? alkyl),-(CH?)pOH,-(CH?)p COO(C?-C? alkyl),-(CH?)pCONR? R?, or R? and R? together represent-(CH?)q-,-O(CH?) rO-or-O(CH? )t-where in the latter the oxygen atom is attached to the 3-or 4-position of the benzene ring; R? and R? are each independently H or C?-C? alkyl; p is 0, 1 or 2; q is 3, 4 or 5; r is 1, 2 or 3; and t is 2, 3 or 4.
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