WO2000050375A1 - Verfahren zur herstellung von [1,1':4',11']-terphenylverbindungen - Google Patents
Verfahren zur herstellung von [1,1':4',11']-terphenylverbindungen Download PDFInfo
- Publication number
- WO2000050375A1 WO2000050375A1 PCT/EP2000/000834 EP0000834W WO0050375A1 WO 2000050375 A1 WO2000050375 A1 WO 2000050375A1 EP 0000834 W EP0000834 W EP 0000834W WO 0050375 A1 WO0050375 A1 WO 0050375A1
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- WO
- WIPO (PCT)
- Prior art keywords
- formula
- acid
- radical
- boronic acid
- boronic
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- 0 *c1ccc(*)cc1 Chemical compound *c1ccc(*)cc1 0.000 description 2
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
Definitions
- the present invention relates to a process for the preparation of [1, 1 ': 4', 1 "] terphenyl compounds which are substituted in the 4" position.
- WO 94/25050 describes a multi-stage process for the preparation of 4 "-n-pentoxyll .l '.r'lterpheny-carboxylic acid (cf. pages 28 and 29 Part A, Part B and Part C).
- a first step 4 "-bromo-4-hydroxybiphenyl is reacted with an n-pentyl halide to give the corresponding 4'-bromo-4-n-pentoxybiphenyl.
- the 4'-bromo-4-n-pentoxybiphenyl is reacted with in a second step Reacted n-butyllithium at -78 ° C., 4′-lithium-4-n-pentoxybiphenyl being formed by transmetallation, which is also reacted in a further step with triisopropyl borate at -78 ° C.
- WO 94/25050 only gives yields for the stages (Part A and Part B) until the formation of 4- (4-n-pentyloxyphenyl) phenylboronic acid.
- Part C which relates to the preparation of the 4 "-n-pentoxy [1, 1 ': 4', 1"] terphenyl-4-carboxylic acid, does not give any indication of the yield.
- EP 0 561 639 describes the preparation of the 4 "-n-pentoxy [1, r: 4M"] te henyl-4-carboxylic acid methyl ester using the abovementioned reaction steps 2, 3 and 4, step 4 instead of 4-iodobenzoic acid the 4-iodobenzoic acid methyl ester is used.
- the yield is 44% for the 4'-n-pentoxybiphenyl-4-boronic acid and 64% for its reaction with the 4-iodobenzoic acid methyl ester (cf. details on page 26, Tables 15 and 16, 2nd line in each case), that is, the Overall yield is only 28.2% based on 4'-bromo-4-n-pentoxybiphenyl.
- the method described above has several disadvantages. On the one hand, it is necessary to start from a very pure 4'-bromo-4-hydroxybiphenyl, which should contain as little Br positional isomer as possible, in order to meet the required isomer quality in the end product.
- the transmetallation according to step 2 is quite complex since it has to be carried out at very low temperatures. If this reaction is not kept in a certain temperature range and / or the reaction times are too long, there arises due to dimerization of the corresponding 4> 4 "-di-n-pentoxy [1,1: 4, 1": 4 " , 1 '"] quaterphenyl. However, this connection can only be separated from the desired end product with great effort.
- step 3 is also carried out at a very low temperature.
- Another disadvantage is that the 4 "-pentoxy [1, 1 ': 4', 1"] terphenyl-4-carboxylic acid is obtained as an obviously heavily contaminated crude product which has to be purified by chromatography on silica gel.
- the object is to provide a method which avoids the disadvantages described above and can be carried out with a justifiable effort.
- R is hydrogen or a straight-chain or branched (C 1 -C 4 ) alkyl radical, in particular hydrogen, a (C 1 -C 2 ) alkyl radical or C (CH 3 ) 3
- R 1 is hydrogen, a straight-chain or branched (CrC4) alkyl radical or a straight-chain or branched (C 1 -C 4 ) alkoxy radical, in particular hydrogen, a (C 1 -C 2 ) alkyl radical or (C 1 -C 2 ) alkoxy radical, preferably hydrogen
- R 2 hydrogen, a straight-chain (C 1 -C 2 ) -alkyl radical, an unsubstituted phenyl radical, a phenyl radical substituted by one or two (C 1 -C 4 ) alkyl groups or (CrC 4 ) alkoxy groups or a radical - (CH 2 ) x OR 3 , where x is an integer from 1 to 4 and R 3 represents a straight-
- A is a monovalent metal or MeX, where Me is a divalent metal and X is CI, Br or I, and R 2 is A or a trisubstituted silyl radical or has the meaning given in formula (1), except hydrogen, with a boric acid ester at -80 to 40 ° C, in the presence of an inert solvent, the reaction product by hydrolysis in a boronic acid of the formula
- R and R 1 have the meaning given in formula (1) and D for CI, Br, I, 03S-C n F2n + ⁇ - where n is an integer from 1 to 4, or N 2 + Y " , wherein Y is " CIO4 " , BF 4 " or HSO 4 " , is reacted at 40 to 180 ° C in the presence of a catalyst and a polar solvent.
- the metal aryl of the formula (2) can be prepared by reacting a benzene derivative correspondingly halogenated in the p-position, for example with Mg or a Li-alkyl.
- a quaterphenyl compound which is difficult to separate from the desired end product, does not take place.
- the reaction of the metal aryl with boric acid ester does not always require the low temperatures specified in WO 94/25050.
- the process is particularly simple if a metal aryl of the formula (2) in which A is MgCl, MgBr or Mgl, in particular MgCl or MgBr, preferably MgCl, is used.
- a metal aryl of the formula (2) in which R 2 is A or a trisubstituted silyl radical or has the meaning given in the compound of the formula (1) but cannot be hydrogen is used.
- the trisubstituted silyl radical in the metal aryl represents a radical SiR R 5 R 6 , in which the radicals R 4 , R 5 and R 6 are the same or different and a phenyl radical or a (C 1 -C 4 ) -alkyl radical, in particular the same and a ( C ⁇ -C) alkyl radical.
- the silyl radical acts as a protective group which can be easily split off after the reaction, the corresponding phenol group being formed.
- a particularly suitable trisubstituted silyl radical is the Si (CH 3 ) 3 radical.
- a boric acid ester B (OR ') 3 is used , in which R' is identical or different and is a straight-chain or branched (Ci-C ⁇ J-alkyl radical, an unsubstituted or by one or two (-CC) -alkyl groups or (C1- C4) - Alkoxy-substituted phenyl radical, in particular for a straight-chain or branched (C ⁇ -C 4 ) alkyl radical, an unsubstituted or substituted by one or two (C ⁇ -C 4 ) alkyl groups, preferably for a straight-chain or branched (C ⁇ -C 4 ) -Alkylrest or an unsubstituted Phenylrest.particularly preferably stands for a straight-chain or branched (-C-C 4 ) alkyl radical.
- boric acid esters the radicals R 'of which are the same, are particularly readily accessible, boric acid esters of the type mentioned above, the radicals of which R' are the same, are used in a large number of cases.
- boric acid esters are trimethyl borate, triethyl borate, tri-n-propyl borate,
- Triisopropyl borate, tri-n-butyl borate and triisobutyl borate is carried out, as already mentioned at the beginning, at -80 to + 40 ° C., in particular -70 to 10 ° C., preferably -40 to 0 ° C.
- the inert solvent used is, for example, a dialkyl ether with 1 to 4 carbon atoms per alkyl radical, a cycloaliphatic ether with 4 or 5 carbon atoms in the ring, for example tetrahydrofuran or 1,4-dioxane, a formaldehyde dialkylacetal, a 1,2- Dialkyl glycol ether with 1 to 4 carbon atoms per alkyl radical, a mixture thereof or a mixture thereof with toluene, in particular a dialkyl ether with 1 to 4 carbon atoms per alkyl radical, tetrahydrofuran, a 1,2-dialkyl glycol ether with 1 to 4 carbon atoms each Alkyl radical, a mixture thereof or a mixture thereof with toluene, preferably tetrahydrofuran,
- a dialkyl ether with 1 to 4 carbon atoms per alkyl radical a cycloaliphatic ether with 4 or 5 carbon atoms
- Dibutyl glycol ether methyl tert-butyl ether, diethyl ether, diisopropyl ether, di-n-butyl ether, a mixture thereof or a mixture thereof with toluene.
- the reaction of the boric acid ester with the metal aryl leads to a salt-like addition product (borate salt).
- the reaction product which may contain radical A or the trisubstituted silyl radical as radical R 2 and any unreacted metal aryl still present is decomposed by bringing the reaction mixture together with water or a water-ice mixture.
- the hydrolysis of the reaction product like that of the metal aryl, proceeds very rapidly, since both the salt-like addition product and the metal aryl react very quickly with water even at low temperatures.
- the boronic acid (3) is formed and salts are formed which are attributable to the reaction product and, if appropriate, to any hydrolyzed metal aryl still present.
- the aqueous mixture obtained is acidified, for example by adding a mineral acid, in particular hydrochloric acid or sulfuric acid.
- a mineral acid in particular hydrochloric acid or sulfuric acid.
- a phase separation is then carried out and the organic phase containing the inert solvent and the boronic acid is separated off.
- the phase separation can be supported by adding a suitable inert solvent, for example ether, methylene chloride, chloroform, toluene, chlorobenzene.
- Water is added to the separated organic phase in order to dissolve any salts which may still be present, and the inert solvent and any solvent used to assist in phase separation are distilled off.
- the boronic acid precipitates as a solid. They are filtered off and dried. If the drying is carried out at temperatures -> 30, in particular ⁇ 50 ° C, the boronic acid begins to split off water with the formation of the corresponding anhydride.
- the formation of the boronic anhydrides depends on the one hand on the level of the temperature and on the other hand on the time during which the temperature acts on the boronic acid. High temperatures and long exposure times favor the formation of boronic anhydride.
- boronic anhydride for example by means of an aqueous alkali, and to release the boronic acid by subsequently acidifying the aqueous solution containing boronic acid salt.
- a mixture of boronic acid and boronic anhydride forms in a large number of cases.
- the boronic anhydride is cyclic anhydride, in particular trimeric boronic anhydride. Mixtures of anhydrides may possibly also form.
- the boronic acid, the boronic anhydride and the mixture of boronic acid and boronic anhydride can - if desired - be recrystallized in one clean suitable solvents, for example aliphatic, cycloaliphatic and / or aromatic hydrocarbons.
- the boronic acid, the boronic anhydride or the mixture containing boronic acid and boronic anhydride is reacted with an alcohol.
- This esterification takes place according to common methods.
- a catalyst, for example an acid, need not be added.
- the boronic acid, the boronic anhydride or the mixture of boronic acid and boronic anhydride may function as a catalyst.
- the esterification is usually allowed to proceed at 50 to 150 ° C., in particular 60 to 140 ° C.
- entraining agents include pentane, hexane, heptane, cyclopentane, cyclohexane, toluene, xylene, ethylbenzene, mesitylene, dichloromethane, chloroform, carbon tetrachloride, trichlorethylene, chlorobenzene, dichlorobenzene, chlorotoluene or dichlorotoluene.
- the alcohol used is a (-C 8 -C) alkyl alcohol, a (C 2 -C 6 ) alkanediol-1, 2, a (C 3 -C 6 ) -alkanediol-1, 3, a (C 4 -C 6 ) -alkanediol-1, 4 or 1, 2-dihydroxybenzene, in particular a (d-C ⁇ J-alkyl alcohol, a (C 2 -C 6 ) -alkanediol-1, 2 or a (C 3 -C 6 ) -alkanediol- 1, 3, preferably a (-C 1 -C) alkyl alcohol, a (C 2 -C 4 ) alkanediol or a (C 3 -C 5 ) alkanediol-1, 3.
- alkyl alcohols are methanol, ethanol, n-propanol, i-propanol, n-butanol, i-butanol, n-pentanol, 2-methylpentanol, n-hexanol, 2-ethylhexanol, in particular methanol, ethanol, n-propanol, i -Propanol, n-butanol and i-butanol.
- Suitable alkanediols are, for example, ethylene glycol, 1,3-propanediol and 2,2-dimethyl-1,3-propanediol (3) (neopentyl glycol).
- the reaction of the boronic acid ester or the boronic acid, the boronic anhydride or the mixture of boronic acid and boronic anhydride takes place - as already mentioned - at 40 to 180 ° C, in particular 50 to 130 ° C, preferably 60 to 120 ° C.
- Acid-binding agents which can be used are amines, for example aliphatic amines, in particular trialkylamines, basic salts of organic and inorganic acids, in particular alkali metal salts and alkaline earth metal salts of organic and inorganic acids, for example Na acetate, K acetate, Na 3 PO, K 3 PO 4 , NaHCO 3 , KHC0 3 , Na 2 CO 3l K 2 C0 3 , MgC0 3 , CaC0 3 , or alkali oxides, alkali hydroxides, alkaline earth oxides, alkaline earth hydroxides, for example NaOH, KOH, Mg (OH) 2 or Ca (OH) 2l .
- amines for example aliphatic amines, in particular trialkylamines
- basic salts of organic and inorganic acids in particular alkali metal salts and alkaline earth metal salts of organic and inorganic acids, for example Na acetate, K acetate, Na 3 PO, K 3
- suitable acid-binding agents have alkali metal hydrogencarbonates, alkali metal carbonates, alkaline earth metal bicarbonates and alkaline earth metal carbonates, in particular Na 2 C0 3 and K 2 CO 3, Na 2 C ⁇ preferably 3 proven.
- the biphenyl compound of the formula 4 used is, in particular, those in which R is hydrogen or a straight-chain or branched (C 1 -C 4 ) alkyl radical, in particular hydrogen, a (CC 2 ) alkyl radical or C (CH 3 ) 3 , preferably represents CH 3 or C (CH 3 ) 3 , R 1 is hydrogen or a straight-chain or branched (C 1 -C 4 ) alkyl radical or (-C-C 4 ) alkoxy radical, in particular hydrogen, a (dC ⁇ J alkyl radical or (CrC 2 ) alkoxy and D is CI, Br, I or N 2 + Y " , in particular CI, Br or I, preferably Br or I.
- a protic and aprotic dipolar solvent in particular an alcohol, a sulfoxide, a sulfone, an amide and optionally water or a mixture thereof, can be used as the polar solvent.
- sulfoxides are dimethyl sulfoxide and diethyl sulfoxide.
- Sulfolane (thiolan dioxide) is a representative of the sulfone series and dimethylformamide, diethylformamide, dimethylacetamide, diethylacetamide and N-methylpyrrolidone are to be mentioned from the series of amides.
- Palladium, a palladium or a nickel compound are suitable as catalysts.
- Pd metal, Pd (O) complex compounds, Pd (II) complex compounds, Ni (0) complex compounds and Ni (II) complex compounds in particular complex compounds, the phosphines, preferably trisubstituted phosphines such as tri-n-butylphosphine, Use tri-tert-butylphosphine containing triphenylphosphine (PPh 3 ).
- Examples of Pd (0) complex compounds are Pd (PPh 3 ) 4, Pd (dba) 2 .
- Ni (0) complex compounds are Ni (PPh3) 4 and examples of Ni (II) complex compounds are NiCI 2 (PPh 3 ) 2, NiBr 2 (PPh 3 ) 2 , NiCI 2 dppf and NiBr 2 dppf.
- Pd (II) compounds or Ni (II) compounds, for example corresponding salts, can also be used together with the phosphines.
- the corresponding complex compounds are formed in situ.
- Palladium compounds for example PdC, Pd (acetate) 2, are particularly suitable.
- the present invention further relates to the compounds 4-n-pentoxyphenylboronic acid
- 390 g of tetrahydrofuran together with 437 g of trimethyl borate are placed in a standard reaction glass vessel under an inert gas atmosphere, cooled to -20 ° C. and mixed with 3000 g of a 29% solution of 4-pentoxyphenylmagnesium chloride in tetrahydrofuran so that the internal temperature does not exceed -15 ° C.
- the white suspension is carefully added to a mixture of 1135 g of water and 1135 g of ice, and the resulting mixture is adjusted to pH 1-2 using 325 g of 60% strength sulfuric acid.
- the pure boronic acid is obtained from the originally obtained mixture of boronic acid with the trimeric anhydride by dissolving the mixture in excess sodium hydroxide solution in the heat and after cooling by adding half-conc. Hydrochloric acid with ice cooling the free boronic acid precipitates. After filtration and washing with water, water-moist 4-n-pentoxyphenylboronic acid with a melting point of 75-80 ° C. (pressed onto clay) is obtained, which to a certain extent forms the trimeric anhydride during drying (e.g. in a drying cabinet).
- 4-Pentoxyphenylboronic acid IR spectrum ⁇ : 3334 (OH), 2940, 1607, 1413, 1346, 1287, 1259, 1182, 1172, 1158, 1113, 1098, 1021, 997, 818 cm- 1 .
- the pure boronic acid is obtained from the originally obtained mixture of the boronic acid with the trimeric anhydride by either azeotropically dehydrating the mixture in toluene and then precipitating the anhydride with cyclopentane after removing the toluene, or the mixture at 50 ° C. in a drying oven in a vacuum until dries to constant weight.
- the trimeric 4-n-pentoxyphenylboronic anhydride has a melting point of 102-103 ° C.
- 4-n-pentoxyphenylboronic acid (2,2-dimethyl-1, 3-diol) ester is filtered off and dried in vacuo at room temperature. 595 g of 4-pentoxyphenylboronic acid (2,2-dimethylpropan-1,3-diol) ester (4-n-pentoxyphenylboronic acid-neopentyl glycol ester) of melting point 80-82 ° are obtained.
- 32.4 g of 4'-iodobiphenyl-4-carboxylic acid are introduced together with 25.8 g of 4-n-pentoxyphenyl-boronic acid glycol ester and 15.9 g of sodium carbonate in 300 ml of methanol / ethylene glycol 9: 1, with intensive stirring at 70 mg of PdC (P h3) 2 were added and the mixture was stirred under reflux for 6 hours.
- the warm reaction mixture is carefully poured onto a mixture of 30 g of 37% sulfuric acid and 200 g of water and heated to 90-100 ° C. for 30 minutes. After filtration and washing with water, the crude product is dried at 80 ° C./100 mbar and then recrystallized from dimethylacetamide. After drying, this gives 28.9 g (80%) of 4 "-n-pentoxy [1, 1 ': 4', 1"] te ⁇ henyl-4-carboxylic acid with a purity> 99%.
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
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Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2000600960A JP2002537369A (ja) | 1999-02-24 | 2000-02-02 | [1,1’:4’,1”]−テルフェニル化合物の製造法 |
DE50006245T DE50006245D1 (de) | 1999-02-24 | 2000-02-02 | Verfahren zur herstellung von (1,1':4',1'')-terphenylvebindungen |
US09/914,478 US6762315B1 (en) | 1999-02-24 | 2000-02-02 | Method for producing (1,1′,4, 11″)-terphenyl compounds |
EP00909137A EP1156997B1 (de) | 1999-02-24 | 2000-02-02 | Verfahren zur herstellung von (1,1':4',1'')-terphenylvebindungen |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19907904.8 | 1999-02-24 | ||
DE19907904A DE19907904A1 (de) | 1999-02-24 | 1999-02-24 | Verfahren zur Herstellung von [1,1':4',1"]-Terphenylverbindungen |
Publications (1)
Publication Number | Publication Date |
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WO2000050375A1 true WO2000050375A1 (de) | 2000-08-31 |
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ID=7898660
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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PCT/EP2000/000834 WO2000050375A1 (de) | 1999-02-24 | 2000-02-02 | Verfahren zur herstellung von [1,1':4',11']-terphenylverbindungen |
Country Status (5)
Country | Link |
---|---|
US (1) | US6762315B1 (de) |
EP (1) | EP1156997B1 (de) |
JP (1) | JP2002537369A (de) |
DE (2) | DE19907904A1 (de) |
WO (1) | WO2000050375A1 (de) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002308808A (ja) * | 2001-02-08 | 2002-10-23 | Honshu Chem Ind Co Ltd | 新規な4,4”−ジヒドロキシ−p−ターフェニル類 |
JP2003212799A (ja) * | 2001-11-19 | 2003-07-30 | Sumitomo Chem Co Ltd | 置換芳香族化合物の製造方法 |
EP1397336A2 (de) * | 2001-02-26 | 2004-03-17 | Honeywell International Inc. | Herstellung von polyarylcarbonsäuren |
WO2004099170A2 (en) * | 2003-04-30 | 2004-11-18 | The Institutes For Pharmaceutical Discovery, Llc | Phenyl substituted carboxylic acids as inhibitors of protein tyrosine phosphatase-1b |
Families Citing this family (5)
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WO2004113258A1 (ja) * | 2003-06-20 | 2004-12-29 | Shionogi & Co., Ltd. | 炭素−炭素結合生成反応 |
JP2008504225A (ja) * | 2004-02-17 | 2008-02-14 | ジョンソン,トーマス,イー. | 大環状化合物を形成するための方法、組成物および装置 |
US8566032B2 (en) * | 2009-10-30 | 2013-10-22 | CSR Technology Holdings Inc. | Methods and applications for altitude measurement and fusion of user context detection with elevation motion for personal navigation systems |
MX2013006040A (es) | 2010-12-07 | 2013-08-26 | Amira Pharmaceuticals Inc | Antagonistas del receptor de acido lisofosfatidico y su uso en el tratamiento de fibrosis. |
CN103570530B (zh) * | 2012-07-26 | 2016-08-10 | 鲁南新时代生物技术有限公司 | 一种阿尼芬净侧链中间体的制备方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1994025050A1 (en) * | 1993-05-04 | 1994-11-10 | Merck & Co., Inc. | Cyclohexapeptidyl propanolamine compounds |
EP0637624A1 (de) * | 1993-08-03 | 1995-02-08 | Showa Shell Sekiyu Kabushiki Kaisha | Antiferroelektrische Flüssigkristallverbindung |
US5693611A (en) * | 1996-02-01 | 1997-12-02 | Eli Lilly And Company | Cyclic peptide antifungal agents |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
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CZ288974B6 (cs) | 1992-03-19 | 2001-10-17 | Eli Lilly And Company | Acylový derivát echinocandinu, způsob jeho přípravy, farmaceutický prostředek s jeho obsahem a jeho pouľití |
-
1999
- 1999-02-24 DE DE19907904A patent/DE19907904A1/de not_active Withdrawn
-
2000
- 2000-02-02 EP EP00909137A patent/EP1156997B1/de not_active Expired - Lifetime
- 2000-02-02 US US09/914,478 patent/US6762315B1/en not_active Expired - Lifetime
- 2000-02-02 JP JP2000600960A patent/JP2002537369A/ja active Pending
- 2000-02-02 DE DE50006245T patent/DE50006245D1/de not_active Expired - Fee Related
- 2000-02-02 WO PCT/EP2000/000834 patent/WO2000050375A1/de active IP Right Grant
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1994025050A1 (en) * | 1993-05-04 | 1994-11-10 | Merck & Co., Inc. | Cyclohexapeptidyl propanolamine compounds |
EP0637624A1 (de) * | 1993-08-03 | 1995-02-08 | Showa Shell Sekiyu Kabushiki Kaisha | Antiferroelektrische Flüssigkristallverbindung |
US5693611A (en) * | 1996-02-01 | 1997-12-02 | Eli Lilly And Company | Cyclic peptide antifungal agents |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002308808A (ja) * | 2001-02-08 | 2002-10-23 | Honshu Chem Ind Co Ltd | 新規な4,4”−ジヒドロキシ−p−ターフェニル類 |
EP1397336A2 (de) * | 2001-02-26 | 2004-03-17 | Honeywell International Inc. | Herstellung von polyarylcarbonsäuren |
EP1397336A4 (de) * | 2001-02-26 | 2005-12-21 | Honeywell Int Inc | Herstellung von polyarylcarbonsäuren |
JP2003212799A (ja) * | 2001-11-19 | 2003-07-30 | Sumitomo Chem Co Ltd | 置換芳香族化合物の製造方法 |
WO2004099170A2 (en) * | 2003-04-30 | 2004-11-18 | The Institutes For Pharmaceutical Discovery, Llc | Phenyl substituted carboxylic acids as inhibitors of protein tyrosine phosphatase-1b |
WO2004099170A3 (en) * | 2003-04-30 | 2005-09-15 | Inst Of Pharmaceutical Discove | Phenyl substituted carboxylic acids as inhibitors of protein tyrosine phosphatase-1b |
JP2006525365A (ja) * | 2003-04-30 | 2006-11-09 | ジ インスチチュート フォー ファーマシューティカル ディスカバリー、エルエルシー | フェニル置換カルボン酸 |
Also Published As
Publication number | Publication date |
---|---|
DE50006245D1 (de) | 2004-06-03 |
US6762315B1 (en) | 2004-07-13 |
JP2002537369A (ja) | 2002-11-05 |
EP1156997A1 (de) | 2001-11-28 |
DE19907904A1 (de) | 2000-08-31 |
EP1156997B1 (de) | 2004-04-28 |
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