WO2008079380A1 - Process for the preparation and isolation of the individual stereoisomers of 1-amino, 3-substituted phenylcyclopentane carboxylates - Google Patents

Process for the preparation and isolation of the individual stereoisomers of 1-amino, 3-substituted phenylcyclopentane carboxylates Download PDF

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Publication number
WO2008079380A1
WO2008079380A1 PCT/US2007/026257 US2007026257W WO2008079380A1 WO 2008079380 A1 WO2008079380 A1 WO 2008079380A1 US 2007026257 W US2007026257 W US 2007026257W WO 2008079380 A1 WO2008079380 A1 WO 2008079380A1
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WO
WIPO (PCT)
Prior art keywords
formula
mixture
compound
compounds
reaction
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Ceased
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PCT/US2007/026257
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English (en)
French (fr)
Inventor
Thomas D. Gordon
Grier A Wallace
Martin E. Hayes
Kirill A. Lukin
Lei Wang
Dilinie P. Fernando
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Abbott Laboratories
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Abbott Laboratories
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Application filed by Abbott Laboratories filed Critical Abbott Laboratories
Priority to JP2009542959A priority Critical patent/JP2010513531A/ja
Priority to CA002673076A priority patent/CA2673076A1/en
Priority to EP07863231.2A priority patent/EP2102145A4/en
Priority to MX2009006748A priority patent/MX2009006748A/es
Publication of WO2008079380A1 publication Critical patent/WO2008079380A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
    • C07C227/18—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/24—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from hydantoins
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/26—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing carboxyl groups by reaction with HCN, or a salt thereof, and amines, or from aminonitriles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/30—Preparation of optical isomers
    • C07C227/34—Preparation of optical isomers by separation of optical isomers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C253/00—Preparation of carboxylic acid nitriles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C253/00—Preparation of carboxylic acid nitriles
    • C07C253/32—Separation; Purification; Stabilisation; Use of additives
    • C07C253/34—Separation; Purification
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C07C45/69—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by addition to carbon-to-carbon double or triple bonds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
    • C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated

Definitions

  • the present invention discloses an effective method for the preparation and isolation of (lR,3R)-methyl l-amino-3-(4- bromophenyl)cyclopentanecarboxylate, (lR,3S)-methyl l-amino-3-(4- bromophenyl)cyclopentanecarboxylate, ( lS,3S)-methyl l-amino-3-(4- bromophenyl)cyclopentanecarboxylate, (lS,3R)-methyl l-amino-3-(4- bromophenyl)cyclopentanecarboxylate, (lR,3R)-l-amino-3-(4- methoxyphenyl)cyclopentanecarboxylate, (lS,3S)-l-amino-3-(4- methoxyphenyl)cyclopentanecarboxylate which is high yielding and provides for enrichment in both diastereomeric
  • SlPl agonists such as those described in WO 2007089715 A2, WO 2006088944 Al and other publications. SlPl agonists are useful, e.g., in the treatment of inflammatory diseases and conditions, and in the treatment of other diseases and conditions.
  • the present invention relates to the efficient and effective synthesis and isolation of (lR,3R)-methyl l-amino-3-(4-bromophenyl)cyclopentanecarboxylate, (lR,3S)-methyl 1-amino- 3-(4-bromophenyl)cyclopentanecarboxylate, (lS,3S)-methyl l-amino-3-(4- bromophenyl)cyclopentanecarboxylate, (lS,3R)-methyl l-amino-3-(4- bromophenyl)cyclopentanecarboxylate, ( 1R.3R.)- 1 -amino-3-(4- methoxyphenyl)cyclopentanecarboxylate, (lS,3S)-l-amino-3-(4- methoxyphenyl)cyclopentanecarboxylate with greater than 90% de and ee.
  • the invention provides a process for the preparation of the mixture of a compound of Formulas 2a and 2b
  • Formula 2a comprising the steps of reacting a compound of Formula 1
  • Formula 2a wherein R is Br or methoxy.
  • the invention provides a process for isolating the compound of Formula 2b
  • R is Br or methoxy
  • the invention provides a process for the preparation of a compound of Formula 3 comprising the steps of reacting a compound of Formula 2b
  • the invention provides a process for preparing a compound of Formula 4
  • the invention provides a process for preparing a compound of Formula 5
  • the invention provides a process for the preparation of a mixture of compounds of Formula 6a and Formula 6b
  • the invention provides a process for the preparation of a mixture of compounds of Formula 7a and Formula 7b
  • Formula 7a comprising the steps of reacting the mixture of compounds of Formula 6a and Formula 6b
  • the invention provides a process for isolating a compound of Formula 8
  • Formula 8 comprising the steps of dissolving the mixture of compounds of Formula 7a and Formula 7b
  • the invention provides a process for the preparation of a compound of Formula 9
  • the invention provides a process for preparing a mixture of compounds of Formula 10a and Formula 10b
  • the invention provides a process for preparing a mixture of compounds of Formula l la and Formula l ib
  • Formula 11a Formula 11 b comprising reacting the mixture of compounds of Formula 10a and Formula 10b
  • the invention provides a process of isolating a compound of Formula 1 Ia
  • the general procedure letter codes constitute a synthetic route to the final product.
  • a worked example of how the route is determined is given below using Example ## as a non- limiting illustration.
  • the synthesis of the example below was completed using general procedure F as detailed in the General Procedures, i.e.,
  • the starting material was prepared using the route (A, H, I, J) (as detailed in the General Procedures). This translates into the following sequence, where the carboxylic acid starting material used in general procedure F is the product of following the procedures A, H, I and J, in the given order.
  • a solution of substituted arylboronic acid (1 - 3 equivalents, preferably 1.5 equivalents) and a rhodium catalyst such as Rh(NBD) 2 BF 4 , hydroxyl[(5)-BINAP]rodium(I) dimer, Rh(acacXC 2 H 4 ) 2 /(K)-BINAP, or acetylacetonatobis(ethylene)rhodium(I) with (R)- or (S)-BINAP, preferably Rh(NBD) 2 BF 4 with (S)-BINAP for (5)-product, Rh(NBD) 2 /BF 4 with (R)-BINAP for (R)-product) (1 - 5 mol %, preferably 1.25 mol %) in an organic solvent (such as tetrahydrofuran, or dioxane, preferably dioxane) and water is degassed with nitrogen.
  • a rhodium catalyst such as Rh(NBD) 2 BF 4 , hydroxy
  • Rh(NBD) 2 BF 4 (22 mg) and S-BINAP (40 mg) are mixed together in degassed 1,4-dioxane (3 mL). The mixture is stirred for 2 h at room temperature to give an orange slurry.
  • 4-bromophenylboronic acid (1 g, 1.5 eq) is dissolved in dioxane (5.6 mL) and water (1.4 mL) at room temperature, and then transferred into the flask containing the catalyst. The resulting suspension is degassed with nitrogen and 2-cyclopenten-l-one (0.273 g, 1 equivalent) and triethylamine (0.336 g, 1 equivalent) are added.
  • the red-orange clear solution is stirred overnight at room temperature.
  • the reaction is separated between ethyl acetate and water, and the organic layer is washed once with 5% NaCl (aqueous), then concentrated.
  • the crude product is further purified on silica gel column using 20% ethyl acetate in heptanes.
  • the reaction mixture is allowed to stir at -78 0 C for 30 min.
  • the reaction mixture is treated with 20 mL of saturated NH 4 Cl and 50 ml of toluene.
  • the aqueous phase is separated and extracted with two 50-mL portions of toluene.
  • the organic phases are combined and concentrated.
  • the residue is further diluted with toluene and concentrated to remove water and then dried in vacuo.
  • the resulting white pasty solid is used directly in the next transformation.
  • the crude borate is transferred to a 200 ml round-bottomed flask equipped with a reflux condenser outfitted with a nitrogen inlet adapter while acetylacetonatobis(ethylene)rhodium(I) (0.166 g, 0.643 mmol) and (R)-BINAP enantiomer (0.480 g, 0.772 mmol) are added in one portion each.
  • the flask is evacuated and filled with nitrogen (three cycles to remove oxygen).
  • dioxane 40 ml
  • cyclopent-2-enone 1.796 ml, 21.43 mmol
  • water 4 ml
  • the resulting suspension is heated at 100 0 C for 16 h.
  • the resulting orange/brown solution is allowed to cool to room temperature.
  • the orange/brown solution is concentrated and the brown residue is taken up in ether and washed with IN HCl solution.
  • a tan emulsion forms.
  • the emulsified mixture is separated and extracted with EtOAc.
  • the aqueous phases are also extracted with EtOAc.
  • the combined organic phases are washed with 10% NaOH and Brine, then concentrated to afford a brown oil.
  • the crude sample is purified via chromatography on silica gel to afforded 1258 mg of colorless oil.
  • a base such as potassium carbonate, or sodium carbonate
  • an organic solvent such as DMF, or DMA (preferably DMF).
  • the mixture is stirred at room temperature for a period of 10 - 30 minutes (preferably about 15 minutes), then methyl iodide (1 - 2 equivalents, preferably 1.1 equivalents) is added.
  • the reaction is stirred at room temperature for a period of 24 - 72 hours (preferably about 48 hours).
  • the reaction mixture is concentrated, cooled down in an ice-water bath, and water is added.
  • the precipitate is collected by filtration to give the crude product.
  • the two stereoisomers can be separated by crystallization.
  • a mixture of N-methyl hydantoins is suspended in an organic solvent (preferably actonitrile) at concentration of approximately Ig per about 1 to about 100 mL (preferably Ig per about 23 mL).
  • organic solvent preferably actonitrile
  • concentration of approximately Ig per about 1 to about 100 mL preferably Ig per about 23 mL.
  • the slurry is heated to about 50 to about 100 0 C with stirring until the solid dissolves. If there solution is not homogeneous the solution is filtered hot. The homogeneous solution is then allowed to cool and aged until significant amounts of solid are present. The solid is collected by filtration.
  • N-alkylated hydantoin (1 equivalent) in a mixture of water and organic solvent (preferably water/dioxane or water/DMSO) is added an inorganic base (such as lithium hydroxide, or sodium hydroxide) (5 - 15 equivalents, preferably about 8 - 10 equivalents).
  • organic solvent preferably water/dioxane or water/DMSO
  • an inorganic base such as lithium hydroxide, or sodium hydroxide
  • a solution of a ketone (1 equivalent) in methanolic ammonia is treated with sodium cyanide (1-4 equivalents, preferably about 2 equivalents) and ammonium chloride (1-4 equivalents, preferably about 2 equivalents), and the mixture is allowed to stir at room temperature for 12-72 hours. Solvents are removed under reduced pressure and the residue is treated with an aqueous base such as sodium carbonate or sodium bicarbonate and the aminonitrile is extracted with an organic solvent such as ethyl acetate or methylene chloride and concentrated.
  • sodium cyanide 1-4 equivalents, preferably about 2 equivalents
  • ammonium chloride 1-4 equivalents, preferably about 2 equivalents
  • the crude product from General Procedure H is re-dissolved in a suitable organic solvent such as methanol or ethyl acetate and treated with a methanolic solution of either D-Tartaric acid or L- Tartartic acid.
  • a suitable organic solvent such as methanol or ethyl acetate
  • the precipitate is washed with a solvent (water, acetonitrile, methanol, ethanol, acetone, or aqueous mixtures of miscible organic solvents) to remove the more soluble diastereomer.
  • the tartrate salt (or bi-tartrate salt) of an ⁇ -aminonitrile is heated with a mixture of 6N HCl and dioxane at a concentration of about 0.1-0.2 g/ml.
  • the mixture is heated at reflux for 4-48 hours (preferably about 18 hours), and then allowed to cool to room temperature.
  • the resulting precipitate is filtered off, washed with water and dried.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Analytical Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
PCT/US2007/026257 2006-12-21 2007-12-21 Process for the preparation and isolation of the individual stereoisomers of 1-amino, 3-substituted phenylcyclopentane carboxylates Ceased WO2008079380A1 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
JP2009542959A JP2010513531A (ja) 2006-12-21 2007-12-21 １−アミノ、３−置換フェニルシクロペンタンカルボン酸エステルの個々の立体異性体の製造および単離方法
CA002673076A CA2673076A1 (en) 2006-12-21 2007-12-21 Process for the preparation and isolation of the individual stereoisomers of 1-amino, 3-substituted phenylcyclopentane carboxylates
EP07863231.2A EP2102145A4 (en) 2006-12-21 2007-12-21 PROCESS FOR THE PREPARATION AND ISOLATION OF INDIVIDUAL STEREOISOMERS OF 1-AMINO, 3-SUBSTITUTED PHENYLCYCLOPENTAN CARBOXYLATES
MX2009006748A MX2009006748A (es) 2006-12-21 2007-12-21 Proceso para la preparacion y aislamiento de los estereoisomeros individuales de fenilciclopentan-carboxilatos 3-sustituidos de 1-amino.

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US87625106P 2006-12-21 2006-12-21
US60/876,251 2006-12-21

Publications (1)

Publication Number Publication Date
WO2008079380A1 true WO2008079380A1 (en) 2008-07-03

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PCT/US2007/026257 Ceased WO2008079380A1 (en) 2006-12-21 2007-12-21 Process for the preparation and isolation of the individual stereoisomers of 1-amino, 3-substituted phenylcyclopentane carboxylates

Country Status (9)

Country Link
US (1) US7956195B2 (https=)
EP (1) EP2102145A4 (https=)
JP (1) JP2010513531A (https=)
CN (1) CN101563316A (https=)
CA (1) CA2673076A1 (https=)
MX (1) MX2009006748A (https=)
RU (1) RU2009128063A (https=)
WO (1) WO2008079380A1 (https=)
ZA (1) ZA200903874B (https=)

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MX2013006867A (es) * 2010-12-22 2013-07-05 Bayer Ip Gmbh Procedimiento para la preparacion de sales de cis-1-amonio-4-alcoxiciclohexanocarbonitrilo.
CN107759483B (zh) * 2016-08-16 2022-03-11 浙江瑞博制药有限公司 一种甲氨基取代的环戊烷甲酸烷基酯的制备方法
CN115847629B (zh) * 2022-11-30 2023-09-29 江苏富乐徳石英科技有限公司 一种高效节能环保的石英环制备工艺

Citations (8)

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Publication number Priority date Publication date Assignee Title
US4841079A (en) * 1987-08-07 1989-06-20 Pfizer, Inc. Process for the production of asymmetric hydantoins
US20050197334A1 (en) * 2002-09-26 2005-09-08 Deping Wang Bifunctional heterocyclic compounds and methods of making and using same
US20050250798A1 (en) * 2004-02-18 2005-11-10 Wyeth Pyrimidoindolones and methods for using same
US20060051846A1 (en) * 2002-09-06 2006-03-09 Kaneka Corporation Process for producing l-alpha-methylcysteine derivative
WO2006088944A1 (en) 2005-02-14 2006-08-24 University Of Virginia Patent Foundation Sphingosine 1- phos phate agonists comprising cycloalkanes and 5 -membered heterocycles substituted by amino and phenyl groups
US20060246553A1 (en) * 2000-09-13 2006-11-02 Ajinomoto Co., Inc. 5-substituted hydantoin racemase, DNA coding for the racemase, and processes for producing optically active amino acids
US20060264457A1 (en) * 2005-05-20 2006-11-23 Pratik Devasthale Pyrrolopyridine-based inhibitors of dipeptidyl peptidase IV and methods
WO2007089715A2 (en) 2006-01-27 2007-08-09 University Of Virginia Patent Foundation Method for treatment of neuropathic pain

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JP3333510B2 (ja) * 1991-10-02 2002-10-15 スミスクライン・ビーチャム・コーポレイション 抗アレルギー、抗炎症および腫瘍壊死因子抑制活性を有するシクロペンタンおよびシクロペンテン誘導体
US5314896A (en) 1991-11-20 1994-05-24 Warner-Lambert Company 1,3-substituted cycloalkenes and cycloalkanes as central nervous system agents
US20020052370A1 (en) * 2000-07-06 2002-05-02 Barber Christopher Gordon Cyclopentyl-substituted glutaramide derivatives as inhibitors of neutral endopeptidase
BRPI0519058A2 (pt) * 2004-12-14 2008-12-23 Astrazeneca Ab composto ou um sal prà-droga farmaceuticamente aceitÁvel do mesmo, mÉtodos para produzir uma inibiÇço da atividade de dgat1 e para tratar diabete melito e/ou obesidade em um animal de sangue quente, uso de um composto, composiÇço farmacÊutica, e, processo para preparar um composto
KR20080096780A (ko) * 2006-02-21 2008-11-03 유니버시티 오브 버지니아 페이턴트 파운데이션 Ｓ１ｐ 수용체 효능제로서의 페닐-시클로알킬 및 페닐-헤테로시클릭 유도체
BRPI0720478A2 (pt) * 2006-12-21 2014-01-14 Abbott Laboratoires Compostos agonistas e antagonistas do receptor esfingosina-1-fosfato

Patent Citations (8)

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Publication number Priority date Publication date Assignee Title
US4841079A (en) * 1987-08-07 1989-06-20 Pfizer, Inc. Process for the production of asymmetric hydantoins
US20060246553A1 (en) * 2000-09-13 2006-11-02 Ajinomoto Co., Inc. 5-substituted hydantoin racemase, DNA coding for the racemase, and processes for producing optically active amino acids
US20060051846A1 (en) * 2002-09-06 2006-03-09 Kaneka Corporation Process for producing l-alpha-methylcysteine derivative
US20050197334A1 (en) * 2002-09-26 2005-09-08 Deping Wang Bifunctional heterocyclic compounds and methods of making and using same
US20050250798A1 (en) * 2004-02-18 2005-11-10 Wyeth Pyrimidoindolones and methods for using same
WO2006088944A1 (en) 2005-02-14 2006-08-24 University Of Virginia Patent Foundation Sphingosine 1- phos phate agonists comprising cycloalkanes and 5 -membered heterocycles substituted by amino and phenyl groups
US20060264457A1 (en) * 2005-05-20 2006-11-23 Pratik Devasthale Pyrrolopyridine-based inhibitors of dipeptidyl peptidase IV and methods
WO2007089715A2 (en) 2006-01-27 2007-08-09 University Of Virginia Patent Foundation Method for treatment of neuropathic pain

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See also references of EP2102145A4

Also Published As

Publication number Publication date
JP2010513531A (ja) 2010-04-30
EP2102145A4 (en) 2014-06-18
RU2009128063A (ru) 2011-01-27
CN101563316A (zh) 2009-10-21
US20080255367A1 (en) 2008-10-16
CA2673076A1 (en) 2008-07-03
ZA200903874B (en) 2010-04-28
EP2102145A1 (en) 2009-09-23
MX2009006748A (es) 2009-06-30
US7956195B2 (en) 2011-06-07

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