- Synthesis process of solifenacin succinate
-
The invention discloses a synthesis process of solifenacin succinate, and relates to the technical field of medicines. The preparation method comprises the following steps: step 1, reacting (R)-quinuclidin-3-ol (B) with a reaction substance to generate (R)-quinuclidin-3-yl carbonochloridate (C); step 2, enabling (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline (A) to react with (R)-quinuclidin-3-yl carbonochloridate (C) to generate solifenacin (D); and step 3, using the solifenacin (D) to prepare the solifenacin succinate. After the technical scheme is adopted, the method has the beneficial effects that in the synthesis process, the problem of low conversion rate caused by direct ester exchange reaction is avoided, meanwhile, the probability of reversible reaction caused by nucleophilic intermediate products generated in the condensation process is also reduced, and the reaction is greatly promoted, so that the yield of solifenacin succinate is increased, the reaction conditions are mild, the operation is simple, the operation procedures are reduced, and the method is suitable for large-scale production.
- -
-
Paragraph 0018; 0020; 0023; 0029
(2021/08/06)
-
- Solifenacin succinate new preparation method
-
The present invention relates to a solifenacin succinate new preparation method which mainly comprises the following steps: 1) formula III compound (R)-(-)-quinuclidin-3-ol and formula IV compound N,N,-N,N-carbonyldiimidazole are reacted to obtain formula V compound (R)-imidazole-1-carboxylic acid-1-azabicyclo[2,2,2] octyl ester; 2) the formula V compound (R)-imidazole-1-carboxylic acid-1-azabicyclo[2,2,2] octyl ester is reacted with formula VI compound (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline to obtain a formula II solifenacin alkaline body; 3) the formula II solifenacin alkaline body isreacted with succinic acid, refined and purified to obtain formula I solifenacin succinate. The preparation method has the advantages that the yield of the solifenacin succinate is high and the purityis high, and the process is simple and suitable for industrial production.
- -
-
Paragraph 0012; 0013
(2018/08/03)
-
- Asymmetric synthesis method for preparation of solifenacin
-
The invention relates to an asymmetric synthesis method for preparation of solifenacin and specifically, discloses a preparation method of solifenacin. The method comprises that ortho-substituted aldehyde as a raw material undergoes a reaction under catalysis of rhodium and a chiral sulfoxide-olefin ligand to produce a key intermediate for high enantioselective addition, and the intermediate is further functionalized and cyclized to form solifenacin. The method is easy to operate, needs mild reaction conditions and has high efficiency and high selectivity.
- -
-
-
- A succinic acid thorley that new preparation method
-
The invention relates to a preparation method of succinic acid solifenacin, and belongs to the technical field of medicinal raw material preparation. According to the technical scheme, the preparation method of the novel succinic acid solifenacin is characterized in that R-3-quinuclidinol, S-1-phenyl-1, 2, 3, 4-tetrahydro naphthalene are used as raw materials, a reaction product of triphosgene and substituted phosphine oxide is used as a condensing agent, the solifenacin is prepared through a one-pot method, and then the succinic acid solifenacin is obtained through salifying. The preparation method of the succinic acid solifenacin has the beneficial effects that the operation is simple, reaction conditions are mild, and the preparation method is suitable for industrial amplification production.
- -
-
-
- A process for the preparation of new thorley that succinic acid
-
The invention relates to a method for preparing a solifenacin succinate ((3R)-1-azabicyclo [2.2.2] octane-3-yl (1S)-1-phenyl-3,4-dihydroisoquinoline-2-(1H)-carboxylate succinate). The method comprises the following steps: 1) preparing a compound (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline carboxylic acid ethyl ester of formula III from a compound (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline, serving as a raw material, of formula IV; 2) synthesizing a compound (3R)-1-azabicyclo [2.2.2] octane-3-yl (1S)-1-phenyl-3,4-dihydroisoquinoline-2-(1H)-carboxylate of formula II in an ionic liquid by using the compound (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline carboxylic acid ethyl ester of formula III; and 3) salifying the compound (3R)-1-azabicyclo [2.2.2] octane-3-yl (1S)-1-phenyl-3,4-dihydroisoquinoline-2-(1H)-carboxylate of formula II in an organic solvent to obtain the compound solifenacin succinate ((3R)-1-azabicyclo [2.2.2] octane-3-yl (1S)-1-phenyl-3,4-dihydroisoquinoline-2-(1H)-carboxylate succinate) of formula I. The preparation method has the advantages that the process is simple, the method is suitable for industrialized production, the yield of the product is high and the purity of the product is high.
- -
-
-
- After-treatment for solifenacin and method for preparing succinic acid solifenacin
-
The invention discloses an after-treatment method for solifenacin. The method comprises the steps that strong acid is slowly dripped into total synthesis liquid of solifenacin, after a pH value is adjusted to be 1.0-2.0, temperature is raised, water is added, and an extracting agent is used for extraction; after a water phase is cooled, a saturated sodium carbonate solution is added to alkalinity, dichloromethane is added to carry out graded extraction, extract liquor is washed with water, and a drying agent is added for drying, so that a dry product is obtained; the dry product is steamed at low temperature to be dry to obtain an oily substance solifenacin. By optimizing the after-treatment technology, isopropyl ether and dichloromethane are only used in the after-treatment technology of solifenacin, types of solvent are reduced, operation and recycle are facilitated, and cost is saved greatly. Strong base or strong acid is not used in the alkali efflorescence process of hydrochloric acid solifenacin, a saturated NaCO3 solution is used, the reaction is mild, temperature can be controlled easily, most importantly, generation of isomers is greatly reduced, and the content of the isomers of a non-structure type (1S and 3R) is reduced.
- -
-
Paragraph 0057; 0058; 0059; 0060
(2016/12/01)
-
- PROCESS FOR PREPARING (1S)-1-PHENYL-3,4-DIHYDRO-2(1H)-ISOQUINOLINE-CARBOXYLATE
-
A process for preparation of (1S)-1-phenyl-3,4-dihydro-2(1H)-isoquinoline-carboxylate (Formula I), comprising reacting (1S)-1-phenyl-3,4-dihydro-2(1H)isoquinoline (Formula II) with carbon dioxide and an alkylating agent R-LG in the presence of a base to obtain the compound of Formula I in an organic solvent. In Formula I and II, R is an alkyl or a substituted alkyl; LG is a leaving group.
- -
-
Paragraph 0037
(2015/09/22)
-
- PROCESS OF PREPARING SOLIFENACIN OR SALT THEREOF, AND NOVEL INTERMEDIATE USED IN THE PROCESS
-
Disclosed herein is a method of preparing solifenacin or a salt thereof, including the steps of: (a) reacting (R)-quinuclidinol with bis(pentafluorophenyl)carbonate in an organic solvent to prepare a solifenacin intermediate, (3R)-1-azabicyclo[2,2,2]oct-3-yl pentafluorophenylcarbonate, and (b) reacting the solifenacin intermediate with (1S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline in an organic solvent to prepare solifenacin. The method is advantageous in that high-purity solifenacin or a salt thereof can be simply and efficiently prepared with high yield using a novel intermediate.
- -
-
Paragraph 0072 - 0083
(2015/04/28)
-
- An improved process for the preparation of highly pure solifenacin succinate via resolution through diastereomeric crystallisation
-
An improved process for the preparation of solifenacin succinate (1) involving resolution through diastereomeric crystallization is described. (1S)-IQL derivative (5) is esterified to form (1S)-ethoxycarbonyl IQL derivative (6) which is condensed with (RS)-3-quinuclidinol (7) to form a solifenacin diastereomeric mixture (8); this is subjected to resolution through diastereomeric crystallization to produce solifenacin succinate (1), which is used for the treatment of an overactive bladder.
- Trinadhachari, Ganala Naga,Kamat, Anand Gopalkrishna,Venkata Balaji, Boddu,Prabahar, Koilpillai Joseph,Naidu, Kolukuluru Mohan,Babu, Korupolu Raghu,Sanasi, Paul Douglas
-
p. 934 - 940
(2014/10/15)
-
- Stereoselective Total Syntheses of Solifenacin and N -Acetyl-1-(4-chloro-phenyl)-6,7-dimethoxytetrahydroisoquinoline
-
A highly stereoselective synthesis of 1-aryl-1,2,3,4-tetrahydroisoquinoline drugs such as solefinacin (muscarinic acetylcholine receptor antagonist) and N-acetyl-1-(4-chlorophenyl)-6,7-dimethoxytetrahydroisoquinoline (AMPA receptor antagonist) has been accomplished using (R)-tert-butanesulfinamide as a chiral source. Chiral tetrahydroisoquinolines have been prepared through the aryl Grignard addition to chiral N-sulfinylimines followed by haloamide cyclization.
- Babu, R. Anji,Reddy, N. Siva Senkar,Reddy, B. Jagan Mohan,Reddy, B. V. Subba
-
p. 2794 - 2798
(2015/11/02)
-
- Enantioselective iridium-catalyzed hydrogenation of 1- and 3-substituted isoquinolinium salts
-
Asymmetric hydrogenation: The title reaction provides an efficient and rapid access to chiral 1- and 3-substituted 1,2,3,4-tetrahydroisoquinolines with excellent enantioselectivity (see scheme; L=ligand). A preliminary mechanistic study indicates that the 1,2-hydride addition might be the initial step in the reaction. The method has been used in the synthesis of urinary antispasmodic drug (+)-solifenacin. Copyright
- Ye, Zhi-Shi,Guo, Ran-Ning,Cai, Xian-Feng,Chen, Mu-Wang,Shi, Lei,Zhou, Yong-Gui
-
p. 3685 - 3689
(2013/04/24)
-
- Engineering an enantioselective amine oxidase for the synthesis of pharmaceutical building blocks and alkaloid natural products
-
The development of cost-effective and sustainable catalytic methods for the production of enantiomerically pure chiral amines is a key challenge facing the pharmaceutical and fine chemical industries. This challenge is highlighted by the estimate that 40-45% of drug candidates contain a chiral amine, fueling a demand for broadly applicable synthetic methods that deliver target structures in high yield and enantiomeric excess. Herein we describe the development and application of a "toolbox" of monoamine oxidase variants from Aspergillus niger (MAO-N) which display remarkable substrate scope and tolerance for sterically demanding motifs, including a new variant, which exhibits high activity and enantioselectivity toward substrates containing the aminodiphenylmethane (benzhydrylamine) template. By combining rational structure-guided engineering with high-throughput screening, it has been possible to expand the substrate scope of MAO-N to accommodate amine substrates containing bulky aryl substituents. These engineered MAO-N biocatalysts have been applied in deracemization reactions for the efficient asymmetric synthesis of the generic active pharmaceutical ingredients Solifenacin and Levocetirizine as well as the natural products (R)-coniine, (R)-eleagnine, and (R)-leptaflorine. We also report a novel MAO-N mediated asymmetric oxidative Pictet-Spengler approach to the synthesis of (R)-harmicine.
- Ghislieri, Diego,Green, Anthony P.,Pontini, Marta,Willies, Simon C.,Rowles, Ian,Frank, Annika,Grogan, Gideon,Turner, Nicholas J.
-
p. 10863 - 10869
(2013/08/23)
-
- PROCESS OF PREPARING SOLIFENACIN OR SALT THEREOF, AND NOVEL INTERMEDIATE USED IN THE PROCESS
-
Disclosed herein is a method of preparing solifenacin or a salt thereof, including the steps of: (a) reacting (R)-quinuclidinol with bis(pentafluorophenyl)carbonate in an organic solvent to prepare a solifenacin intermediate,(3R)-1-azabicyclo[2,2,2]oct-3-yl pentafluorophenylcarbonate, and (b) reacting the solifenacin intermediate with (1S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline in an organic solvent to prepare solifenacin. The method is advantageous in that high-purity solifenacin or a salt thereof can be simply and efficiently prepared with high yield using a novel intermediate.
- -
-
Paragraph 129-131
(2013/10/21)
-
- NOVEL PROCESS FOR THE PREPARATION OF SOLIFENACIN SUCCINATE
-
The present invention relates to a process for the preparation of Solifenacin succinate by condensing a compound of formula (IVb) with (RS)-3-quinuclidinol, wherein, R represents methyl, ethyl, isopropyl; to produce a diastereomeric mixture of (1S)-3,4-dihydro-1-phenyl-2(1H)-isoquinolinecarboxylic acid (3RS)-1-azabicyclo[2.2.2]oct-3-yl ester, which is treated with succinic acid in a solvent or mixture of solvents to produce optically pure Solifenacin succinate, Formula (X).
- -
-
Paragraph 0034; 0035; 0036
(2013/05/22)
-
- PROCESS FOR THE PREPARATION OF SOLIFENACIN AND SALTS THEREOF
-
The invention provides a new process for the preparation of solifenacin or a pharmaceutically acceptable acid addition salt thereof, comprising reacting (R)- quinuclidin-3-yl phenethylcarbamate with benzaldehyde in the presence of an acid to obtain a diasteroisomeric mixture (S,R)-((R)-quinuclidin-3-yl) 1 -phenyl-3,4- dihydroisoquinoline-2(1 H)-carboxylate of formula (IV) which can be resolved and the solifenacin or a pharmaceutically acceptable acid addition salt thereof recovered. The invention also provides the new key intermediate (R)-quinuclidin-3-yl phenethylcarbamate involved in the process. Further the invention provides a method for the transformation of (R)-((R)-quinuclidin-3-yl) 1 -phenyl-3,4- dihydroisoquinoline-2(1 H)-carboxylate into a diasteroisomeric mixture (S,R)-((R)- quinuclidin-3-yl) 1 -phenyl-3,4-dihydroisoquinoline-2(1 H)-carboxylate.
- -
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Page/Page column 21
(2013/02/28)
-
- SOLIFENACIN SALTS
-
The invention concerns fumarate salts of solifenacin, as well as pharmaceutical compositions comprising fumarate salts of solifenacin. The invention furthermore concerns a process for preparing solifenacin and salts thereof. The fumarate salt provides improved properties over the known solifenacin salts, especially in terms of its stability. The novel process for its preparation is furthermore improved over known processes for preparing solifenacin in that it provides a higher yield and recovers a greater amount of starting material.
- -
-
-
- NOVEL PROCESS FOR THE PREPARATION OF SOLIFENACIN SUCCINATE
-
The present invention relates to a process for the preparation of Solifenacin succinate by condensing a compound of formula (IVb) with (RS)-3-quinuclidinol, wherein, R represents methyl, ethyl, isopropyl; to produce a diastereomeric mixture of ( 1S)-3,4-dihydro- 1 -phenyl-2( 1 H)-isoquinolinecarboxylic acid (3RS)- 1 - azabicyclo[2.2.2]oct-3-yl ester, which is treated with succinic acid in a solvent or mixture of solvents to produce optically pure Solifenacin succinate, Formula (X).
- -
-
-
- PROCESS FOR THE PREPARATION OF SOLIFENACIN AND SOLIFENACIN SUCCINATE
-
A process for the preparation of solifenacin wherein all the reaction steps, starting from (i) release of (S) -I -phenyl- 1, 2,3, 4 - tetrahydroisoquinoline from its diastereoisomeric salt with D- (-) - tartaric acid, (ii) conversion of (S) - 1 -phenyl - 1, 2, 3, 4 - tetrahydroisoquinoline into 1 - (5) -phenyl - 1, 2, 3, 4 - tetrahydroisoquinolinecarbonyl chloride in the reaction with triphosgene in the presence of pyridine to (iii) the reaction between 1- (5) -phenyl - 1, 2, 3, 4 - tetrahydroisoquinolinecarbonyl chloride and 3- (S) - quinuclidinol in the presence of sodium hydride are carried out without the isolation of intermediates in solid form and the solvents used for the reactions are aprotic solvent. Resulting solifenacin in the free base form is converted into the corresponding succinic acid salt using methods known in the art.
- -
-
-
- Efficient and single pot process for the preparation of enantiomerically pure solifenacin succinate, an antimuscarinic agent
-
The development of an efficient and economic one-pot process, in which the configuration of the chiral centers of the starting materials is retained, for the preparation of highly pure solifenacin succinate, an antimuscarinic agent, is presented in this communication. The earlier reported processes suffer from the drawbacks of racemization and low yields due to the use of strong base, higher temperatures, and longer reaction times. The present work circumvents these issues by activating (3R)-quinuclidin-3-ol into a mixed active carbonate derivative by treating it with bis(4-nitrophenyl)carbonate. The subsequent reaction of the active carbonate with an enantiomerically pure amine without using any base at ambient temperature provided enantiomerically pure solifenacin with an overall yield of 90%. Graphical Abstract: [Figure not available: see fulltext.]
- Niphade, Navnath C.,Jagtap, Kunal M.,Mali, Anil C.,Solanki, Pavankumar V.,Jachak, Madhukar N.,Mathad, Vijayavitthal T.
-
p. 1181 - 1186
(2012/01/06)
-
- PROCESSES FOR THE PREPARATION OF SOLIFENACIN OR A SALT THEREOF
-
The present invention describes recovery and racemization of (1R)-Phenyl- 1,2,3,4-tetrahydroisoquinoline of compound of formula (III) to obtain racemic 1- phenyl-1, 2,3,4-tetrahydroisoquinoline of compound of formula (I) and its further resolution to get ( IS)-1-phenyl-1, 2, 3, 4-tetrahydroisoquinoline (intermediate B) in high chemical and chiral purity, which is the key intermediate for the preparation of (3R)-azabicyclo[2.2.2]oct-3-yl (1S)-1-phenyl-3,4-dihydroisoquinoline-2-(1H)- carboxylate.
- -
-
-
- A NEW METHOD FOR THE PREPARATION OF SOLIFENACIN AND NEW INTERMEDIATE THEREOF
-
A new method for the preparation of solifenacin by reacting quinuclidin-3-ol and bis (aryl) carbonate to form (3R)-l -azabicyclo[2.2.2]oct-3-yl 4-aryl carbonate of formula (IVa); and treating (3R)-I - azabicyclo[2.2.2]oct-3-yl 4-aryl carbonate of formula (IVa) with (1S)- I -phenyl- 1, 2, 3, 4- tetrahydroisoquinoline in an inert atmosphere to form a Solifenacin base which is converted into its pharmaceutically acceptable salts. The invention also provide new compound, (3R)-1 - azabicyclo[2.2.2]oct-3-yl 4-aryl carbonate, which is used as an intermediate for the preparation of Solifenacin base and a process for the preparation thereof.
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Page/Page column 29
(2010/10/03)
-
- Enantioselective synthesis of 1-aryltetrahydroisoquinolines
-
(Figure presented) 1-Aryltetrahydroisoquinolines (1-arylTHIQs) are important structural motifs in many alkaloids and biologically active compounds. Ligand 2a promotes the enantioselective addition of arylzinc reagents to 3,4-dihydroisoquinoline N-oxide to
- Wang, Sa,Onaran, M. Burak,Seto, Christopher T.
-
supporting information; experimental part
p. 2690 - 2693
(2010/09/03)
-
- Process for the Synthesis of Solifenacin
-
This invention provides improved methods for making solifenacin and pharmaceutically acceptable salts thereof. The instant methods are unexpectedly advantageous in their simplicity and efficiency.
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Page/Page column 6
(2010/03/02)
-
- A PROCESS FOR THE PREPARATION OF SOLIFENACIN SALTS AND THEIR INCLUSION INTO PHARMACEUTICAL DOSAGE FORMS
-
The invention relates to the synthesis of solifenacin, the preparation of its salts and their inclusion into pharmaceutically acceptable dosage forms.
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Page/Page column 33-34
(2010/04/03)
-
- METHOD FOR THE PREPARATION OF SOLIFENACIN
-
A method of preparing (1S)-(3R)-1-azabicyclo[2.2.2]oct-3-yl 3,4-dihydro-1-phenyl-2(1H)-isoquinoline carboxylate (solifenacin) or its pharmaceutically acceptable salts with high optic purity, wherein the crude solifenacin base is transformed to the hydrogen tartrate, which is then optionally transformed to another pharmaceutically acceptable salt or the base of solifenacin. A crystalline salt of solifenacin hydrogen tartrate.
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Page/Page column 3
(2010/06/19)
-
- PROCESS FOR PREPARATION OF SOLIFENACIN AND/OR THE PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF OF HIGH PHARMACEUTICAL PURITY
-
A process for the preparation of solifenacin and/or the pharmaceutically acceptable salts thereof of high pharmaceutical purity is characterized in that 3-(R)-quinuclidinoloxy anion generated in situ from 3-(R)-quinuclidinol in a presence of strong base in polar organic solvent is subject to acylation with (S)-1 -phenyl-1,2,3, 4-tetrahydroisoquinolinecarbonyl chloride of chemical purity at least 98%, while maintaining constant anion excess in a reaction mixture, and after reaction completion solifenacin base is optionally transformed into solifenacin salt according to standard procedures. (S)-1-Phenyl-1,2,3,4-tetrahydroisoquinolinecarbonyl chloride of chemical purity at least 98% is obtained in a reaction of (S)-1-phenyl-1,2,3, 4- tetrahydroisoquinoline and molar excess of phosgene in a presence of tertiary aromatic amine in aromatic hydrocarbon, and isolated in a crystalline form.
- -
-
-
- PROCESS FOR PREPARING CHEMICALLY AND CHIRALLY PURE SOLIFENACIN BASE AND ITS SALTS
-
The present invention provides improved processes for preparing chemically and chirally pure Solifenacin base. The present invention also provides for a composition comprising of a salt of Solifenacin having at least 98 % purity. The present invention also disclose certain new salts of Solifenacin as well as well as new polymorphic forms of Solifenacin hydrochloride and Solifenacin oxalate, in pure form.
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Page/Page column 41
(2009/09/04)
-
- Process for the preparation of solifenacin
-
A process for the preparation of (1S,3′R)-quiniclidin-3′-yl-1-phenyl-3,4-dihydro-1H-isoquinolin-2-carboxylate, namely solifenacin, comprising the reaction of a compound of formula (IV) with a compound of formula (V), as herein defined, and the subsequent reaction with 3-quinuclidinol.
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Page/Page column 3
(2009/08/18)
-
- "Process for the preparation of solifenacin"
-
A process for the preparation of (1S,3'R)-quinielidin-3'-yl-1-phenyl-3,4-dihydro-1H-isoquinolin-2-carboxylate, namely solifenacin, comprising the reaction of a compound of formula (IV) with a compound of formula (V), as herein defined, and the subsequent reaction with 3-quinuclidinol.
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Page/Page column 5-6
(2009/09/05)
-
- PROCESS FOR THE PREPARATION OF SOLIFENACIN
-
A process for the preparation of (1S)-QR)-I -azabicyclo[2.2.2.]oct-3-yl 3,4-dihydro-1-phenyl- 2(1H)-isoquino-line carboxylate by reacting (1S)-alkyl 1-phenyl-1,2,3,4-tetrahydro-2-isoquinoline carboxylate with 3-(R)-quinuclidol in an inert solvent, where a primary alkyl ester of the carboxylate whose alkyl length is C1-C4 is used and the reaction is catalyzed by a non-nu-cleophilic base.
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Page/Page column 3
(2009/08/18)
-
- PROCESSES FOR SOLIFENACIN PREPARATION
-
Processes for preparing solifenacin comprising distilling ethanol and organic solvent from a reaction mixture and recycling the organic solvent are described. The ethanol is removed using a Dean-Stark apparatus. Also described are processes for reducing solifenacin diastereomeric and enantiomeric impurities.
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Page/Page column 16
(2009/03/07)
-
- SOLIFENACIN COMPOSITIONS
-
Compositions and/or formulations comprising solifenacin or a salt thereof and processes for preparing the same. Certain compositions and formulations contain a stable amorphous form of solifenacin succinate.
- -
-
-
- Process for the synthesis of solifenacin
-
The present invention provides an improved synthetic strategy for the preparation of solifenacin and pharmaceutically acceptable salts thereof.
- -
-
Page/Page column 4
(2008/12/07)
-
- A METHOD FOR THE PREPARATION OF SOLIFENACIN
-
A method of preparing (lS)-(3R)-l-azabicyclo[2.2.2]oct-3-yl 3,4-dihydro-l-phenyl-2(lH)- isoquinoline carboxylate (solifenacin) or its pharmaceutically acceptable salts with high optic purity, wherein the crude solifenacin base is transformed to the hydrogen tartrate, which is then optionally transformed to another pharmaceutically acceptable salt or the base of solifenacin. A crystalline salt of solifenacin hydrogen tartrate.
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Page/Page column 5
(2008/12/06)
-
- Process for preparing polymorphic forms of solifenacin succinate
-
Polymorphic forms of solifenacin have been prepared and characterized. These polymorphic forms are particularly useful in pharmaceutical compositions.
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Page/Page column 9
(2008/12/05)
-
- PROCESS FOR PREPARING SOLIFENACIN AND ITS SALTS
-
The present invention relates to solifenacin in solid form and a process for its preparation and to a process for the preparation of (1S)-1-Phenyl-1,2,3,4-tetrahydro-isoquinoline, a key intermediate in the synthesis of solifenacin and its salts.
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Page/Page column 22; 23
(2008/06/13)
-
- PROCESSES FOR PREPARING SOLIFENACIN
-
Provided are new intermediates of solifenacin and methods for their preparation, as well as methods of preparing solifenacin and solifenacin succinate.
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-
Page/Page column 13
(2010/11/27)
-
- SOLIFENACIN-CONTAINING COMPOSITION
-
To provide a novel method for producing a composition comprising solifenacin or a salt thereof, and a composition comprising solifenacin or a salt thereof as produced by the method, wherein an optionally substituted lower alkyl is added to the 2-position of the quinuclidine of solifenacin. The composition of the present invention contains a highly pure solifenacin, while the unexpected compounds specific to the method in an extremely low content, so that it has very preferable properties as a bulk for pharmaceutical products.
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Page/Page column 7
(2010/11/24)
-
- COMPOSITION CONTAINING SOLIFENACIN SUCCINATE
-
A solifenacin succinate-containing composition with less impurities which can be used as a bulk for pharmaceutical is provided. The solifenacin succinate-containing compostiion of the present invention has a reduced content of especially its optical isomers in comparison with the known compositions containing an acid addition salt of solifenacin, so that it can be used for production of a therapeutic agent containing solifenacin succinate. In addition, the above-described solifenacin succinate-containing composition can be easily produced in accordance with the production method of the present invention.
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Page/Page column 9; 10
(2008/06/13)
-
- Synthesis and antimuscarinic properties of quinuclidin-3-yl 1,2,3,4-tetrahydroisoquinoline-2-carboxylate derivatives as novel muscarinic receptor antagonists
-
In the course of continuing efforts to develop potent and bladder-selective muscarinic M3 receptor antagonists, quinuclidin-3-yl 1-aryl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate derivatives and related compounds were designed as conformationally restricted analogues of quinuclidin-3-yl benzhydrylcarbamate (8). Binding assays with rat muscarinic receptor subtypes revealed that the quinuclidin-3-yl 1-aryl-1,2,3,4- tetrahydroisoquinoline-2-carboxylate derivatives showed high affinities for the M3 receptor, and selectivity for the M3 receptor over the M2 receptor. Of these derivatives, (+)-(1S,3'R)-quinuclidin-3'-yl 1-phenyl-l,2,3,4-tetrahydroisoquinoline-2-carboxylate monohydrochloride (9b) exhibited almost the same inhibitory activity against bladder contraction to that of oxybutynin (1), and more than 10-fold selectivity for bladder contraction versus salivary secretion, demonstrating that 9b may be useful for the treatment of symptoms associated with overactive bladder without having side effects such as dry mouth.
- Naito, Ryo,Yonetoku, Yasuhiro,Okamoto, Yoshinori,Toyoshima, Akira,Ikeda, Ken,Takeuchi, Makoto
-
p. 6597 - 6606
(2007/10/03)
-