EP0182061B1 - New process for preparing 2(4-fluorophenyl) alpha methyl-5-benzoxazole acetic acid - Google Patents
New process for preparing 2(4-fluorophenyl) alpha methyl-5-benzoxazole acetic acid Download PDFInfo
- Publication number
- EP0182061B1 EP0182061B1 EP85112699A EP85112699A EP0182061B1 EP 0182061 B1 EP0182061 B1 EP 0182061B1 EP 85112699 A EP85112699 A EP 85112699A EP 85112699 A EP85112699 A EP 85112699A EP 0182061 B1 EP0182061 B1 EP 0182061B1
- Authority
- EP
- European Patent Office
- Prior art keywords
- und
- von
- fluorphenyl
- benzoxazol
- mit
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 238000004519 manufacturing process Methods 0.000 title abstract description 6
- ARPYQKTVRGFPIS-UHFFFAOYSA-N 2-[2-(4-fluorophenyl)-1,3-benzoxazol-5-yl]propanoic acid Chemical compound N=1C2=CC(C(C(O)=O)C)=CC=C2OC=1C1=CC=C(F)C=C1 ARPYQKTVRGFPIS-UHFFFAOYSA-N 0.000 title description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 14
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims abstract description 10
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims abstract description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims abstract description 7
- AOZKIUFHHMUPGU-UHFFFAOYSA-N 2-(3-amino-4-hydroxyphenyl)acetic acid Chemical compound NC1=CC(CC(O)=O)=CC=C1O AOZKIUFHHMUPGU-UHFFFAOYSA-N 0.000 claims abstract description 6
- CZKLEJHVLCMVQR-UHFFFAOYSA-N 4-fluorobenzoyl chloride Chemical compound FC1=CC=C(C(Cl)=O)C=C1 CZKLEJHVLCMVQR-UHFFFAOYSA-N 0.000 claims abstract description 6
- 150000002148 esters Chemical class 0.000 claims abstract description 5
- 239000000243 solution Substances 0.000 claims description 20
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 16
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 12
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 5
- 235000011149 sulphuric acid Nutrition 0.000 claims description 5
- 235000011007 phosphoric acid Nutrition 0.000 claims description 3
- -1 4-Fluorphenyl Chemical group 0.000 claims 2
- 229940035423 ethyl ether Drugs 0.000 claims 1
- 229910052763 palladium Inorganic materials 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 abstract description 11
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 abstract description 6
- 235000019441 ethanol Nutrition 0.000 abstract description 6
- KHPXUQMNIQBQEV-UHFFFAOYSA-L oxaloacetate(2-) Chemical compound [O-]C(=O)CC(=O)C([O-])=O KHPXUQMNIQBQEV-UHFFFAOYSA-L 0.000 abstract description 6
- KBFHXGWZGIITPB-UHFFFAOYSA-N 2-[2-(4-fluorophenyl)-1,3-benzoxazol-5-yl]acetic acid Chemical compound N=1C2=CC(CC(=O)O)=CC=C2OC=1C1=CC=C(F)C=C1 KBFHXGWZGIITPB-UHFFFAOYSA-N 0.000 abstract description 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 abstract description 3
- WYACBZDAHNBPPB-UHFFFAOYSA-N diethyl oxalate Chemical compound CCOC(=O)C(=O)OCC WYACBZDAHNBPPB-UHFFFAOYSA-N 0.000 abstract description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 abstract description 3
- 239000002253 acid Substances 0.000 abstract description 2
- 238000005984 hydrogenation reaction Methods 0.000 abstract description 2
- 239000000047 product Substances 0.000 description 22
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
- 239000000203 mixture Substances 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 238000002844 melting Methods 0.000 description 7
- 230000008018 melting Effects 0.000 description 7
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 238000013019 agitation Methods 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000012429 reaction media Substances 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
- 239000007832 Na2SO4 Substances 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 235000015320 potassium carbonate Nutrition 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- QBHBHOSRLDPIHG-UHFFFAOYSA-N (4-hydroxy-3-nitrophenyl)acetic acid Chemical compound OC(=O)CC1=CC=C(O)C([N+]([O-])=O)=C1 QBHBHOSRLDPIHG-UHFFFAOYSA-N 0.000 description 1
- YLOVYLOYLHRGAG-UHFFFAOYSA-N 2-(4-hydroxy-3-nitrophenyl)propanenitrile Chemical compound N#CC(C)C1=CC=C(O)C([N+]([O-])=O)=C1 YLOVYLOYLHRGAG-UHFFFAOYSA-N 0.000 description 1
- ZQZQELQTUVDYME-UHFFFAOYSA-N 2-(4-methoxy-5-phenylthiophen-3-yl)prop-2-enoic acid Chemical compound OC(=O)C(=C)C1=CSC(C=2C=CC=CC=2)=C1OC ZQZQELQTUVDYME-UHFFFAOYSA-N 0.000 description 1
- LLKOGADZFSZCHH-UHFFFAOYSA-N 2-(4-methoxy-5-phenylthiophen-3-yl)propanoic acid Chemical compound OC(=O)C(C)C1=CSC(C=2C=CC=CC=2)=C1OC LLKOGADZFSZCHH-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 238000009876 asymmetric hydrogenation reaction Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- LJWKFGGDMBPPAZ-UHFFFAOYSA-N ethoxyethane;toluene Chemical compound CCOCC.CC1=CC=CC=C1 LJWKFGGDMBPPAZ-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229960003424 phenylacetic acid Drugs 0.000 description 1
- 239000003279 phenylacetic acid Substances 0.000 description 1
- 229960002895 phenylbutazone Drugs 0.000 description 1
- VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 1
- 239000011369 resultant mixture Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
- C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
- C07D263/56—Benzoxazoles; Hydrogenated benzoxazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D263/57—Aryl or substituted aryl radicals
Definitions
- This invention relates to a process for preparing 2(4-fluorophenyl) ⁇ -methyl-5-benzoxazole acetic acid.
- (+)-2(4-fluorophenyl) ⁇ -methyl-5-benzoxazole acetic acid is known for example from British patent 1,495,488 and Italian patent 22454 A/82.
- stage A 4-hydroxy-3-aminophenylacetic acid (II) is reacted with 4-fluorobenzoyl chloride (III) to produce 3(4-fluoro)-benzamido-4-hydroxyphenylacetic acid (IV).
- the reaction is conducted in a reaction medium constituted by a 2%-5% aqueous sodium bicarbonate solution operating at a temperature of between 0° and 30°C, for a time of between 3 and 6 hours.
- the product (IV) is obtained with a yield of about 95%.
- stage B in which the heterocyclic ring is formed, the product (IV) is treated with a 70-80 weight % phosphoric acid solution at a temperature of 120°-125°C for a time of between 30 minutes and 1 hour.
- the product (V) is obtained with a yield of between 90% and 95%.
- stage C) the product (V) is esterified by treatment with ethyl alcohol in the presence of H2SO4, by heating under reflux for some hours to obtain ethyl (4-fluorophenyl)5-benzoxazole acetate (VI) with a yield of 80%-85%.
- stage D) the ester (VI) is reacted with diethyloxalate in the presence of sodium methylate in a reaction medium constituted by an ether or an hydrocarbon solvent.
- a reaction medium constituted by an ether or an hydrocarbon solvent.
- the mixture is heated to boiling under reflux for 20-30 hours and is then cooled and neutralised with a 5% H2SO4 solution.
- the organic phase is washed with a saturated NaCl solution and then with H2O and dried by treatment with Na2SO4, after which it is concentrated to a small volume to obtain ethyl 2(4-fluorophenyl)-5-benzoxazole oxalacetate (VII) with a yield of between 90% and 95%.
- stage E the product (VII) is treated with formaldehyde in an aqueous K2CO3 solution at ambient temperature under agitation, for a time of 4-6 hours.
- Ethyl 2(4-fluorophenyl)5-benzoxazole acrylate (VIII) is thus obtained, with a yield exceeding 95%.
- stage F the ester (VIII) is hydrolysed to obtain the corresponding acid by firstly treating it in a tetrahydrofuran solution with a KOH solution at ambient temperature for 20-30 hours and then acidifying with a solution of HCl in t-butylmethylether.
- stage G the product (IX) is hydrogenated under atmospheric pressure at a temperature of 25°-40°C, using 5% Pd-on-carbon as catalyst in a reaction medium constituted by ethyl alcohol.
- the catalyst is separated by filtration in a nitrogen environment, and the aqueous solution is used for the reaction with 4-fluorobenzoyl chloride, which is carried out in the following manner: the aqueous solution is cooled to 5°C in a nitrogen environment, 460 ml of t-butylmethylether are added, and then 74 ml of 4-fluorobenzoyl chloride dissolved in 170 ml of t-butylmethylether are fed slowly.
- the mixture is agitated vigorously for 6 hours at ambient temperature, after which it is filtered to recover the product. A further small quantity of product is recovered from the mother liquors by evaporating the solvent.
- 127 g of finely ground 3(4-fluoro)benzamido-4-phenylacetic acid are added to 1 litre of a 75 weight % phosphoric acid solution heated to 130°C and under agitation. The heating is continued to 125°C for 30 minutes to obtain complete dissolving, after which the solution is cooled to 50°C and water is slowly added until the product crystallises. Further water is added to form a total quantity of 3 litres, and agitation is continued for 2 hours. The mixture is filtered, the solid is pulped in distilled water, refiltered and dried.
- the resultant mixture is heated to boiling under reflux for 24 hours, and is then cooled and neutralised with 5% sulphuric acid.
- the organic phase is washed firstly with a saturated sodium chloride solution and then with water, and is finally dried by treatment with sodium sulphate.
- the mixture is agitated for 5 hours at ambient temperature and is then extracted with t-butylmethylether.
- the solution is partly evaporated under vacuum at 40°C, cooled to ambient temperature, 500 ml of t-butylmethylether are added, and the mixture acidified with dilute (1:10) HCl to pH 2.
- the ether phase is separated, and the aqueous phase is extracted twice with ether.
- the pooled ether solution is dried and evaporated.
- the catalyst is separated by filtration, and the solution is concentrated to a small volume.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AT85112699T ATE70832T1 (de) | 1984-10-22 | 1985-10-07 | Verfahren zur herstellung von 2-(4-fluorphenyl)alpha-methyl-5-benzoxazolessigs|ure. |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT2326484 | 1984-10-22 | ||
| IT23264/84A IT1177017B (it) | 1984-10-22 | 1984-10-22 | Processo per la preparazione dell'acido 2(4-flurofenil)alfa-metil-5-benzox azoloacetico |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EP0182061A1 EP0182061A1 (en) | 1986-05-28 |
| EP0182061B1 true EP0182061B1 (en) | 1991-12-27 |
Family
ID=11205428
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP85112699A Expired - Lifetime EP0182061B1 (en) | 1984-10-22 | 1985-10-07 | New process for preparing 2(4-fluorophenyl) alpha methyl-5-benzoxazole acetic acid |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US4652654A (cs) |
| EP (1) | EP0182061B1 (cs) |
| JP (1) | JPS61100574A (cs) |
| AT (1) | ATE70832T1 (cs) |
| DE (1) | DE3585022D1 (cs) |
| IT (1) | IT1177017B (cs) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1233836B (it) * | 1988-01-13 | 1992-04-21 | Euroresearch Srl | Sali idrosolubili dell'acido (+)2-(4 fluorofenil)-alfa-metil-5 benzoxazolo acetato. |
| GB9312853D0 (en) * | 1993-06-22 | 1993-08-04 | Euro Celtique Sa | Chemical compounds |
| US5591776A (en) * | 1994-06-24 | 1997-01-07 | Euro-Celtique, S.A. | Pheynl or benzyl-substituted rolipram-based compounds for and method of inhibiting phosphodiesterase IV |
| US5922751A (en) * | 1994-06-24 | 1999-07-13 | Euro-Celtique, S.A. | Aryl pyrazole compound for inhibiting phosphodiesterase IV and methods of using same |
| US6372770B1 (en) | 1994-10-12 | 2002-04-16 | Euro-Celtique, S.A. | Benzoxazoles |
| US5665737B1 (en) * | 1994-10-12 | 1999-02-16 | Euro Celtique Sa | Substituted benzoxazoles |
| FI971489L (fi) * | 1994-10-12 | 1997-06-05 | Euro Celtique Sa | Uusia bentsoksatsoleja |
| US6025361A (en) * | 1994-12-13 | 2000-02-15 | Euro-Celtique, S.A. | Trisubstituted thioxanthines |
| ATE247655T1 (de) * | 1994-12-13 | 2003-09-15 | Euro Celtique Sa | Dreifachsubstituierte thioxanthine |
| ATE247116T1 (de) * | 1994-12-13 | 2003-08-15 | Euro Celtique Sa | Arylthioxanthine |
| US6166041A (en) * | 1995-10-11 | 2000-12-26 | Euro-Celtique, S.A. | 2-heteroaryl and 2-heterocyclic benzoxazoles as PDE IV inhibitors for the treatment of asthma |
| US6075016A (en) * | 1996-04-10 | 2000-06-13 | Euro-Celtique S.A. | 6,5-fused aromatic ring systems having enhanced phosphodiesterase IV inhibitory activity |
| US5864037A (en) | 1996-06-06 | 1999-01-26 | Euro-Celtique, S.A. | Methods for the synthesis of chemical compounds having PDE-IV inhibitory activity |
| US5744473A (en) * | 1996-09-16 | 1998-04-28 | Euro-Celtique, S.A. | PDE IV inhibitors: "bis-compounds" |
| CN1222513C (zh) | 1997-02-03 | 2005-10-12 | 富士写真菲林株式会社 | 卤化银彩色照相感光材料和其中所用的菲尼酮化合物以及这类化合物的制备方法 |
| CN102459192B (zh) * | 2009-05-15 | 2015-06-24 | 赛诺菲 | 制备用作TAFIa抑制剂的化合物的方法 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1435721A (en) * | 1972-05-18 | 1976-05-12 | Lilly Industries Ltd | Benzoxazole derivatives |
| US3962452A (en) * | 1972-05-18 | 1976-06-08 | Lilly Industries, Ltd. | Benzoxazole derivatives as therapeutics |
| US4025636A (en) * | 1973-10-23 | 1977-05-24 | Lilly Industries, Ltd. | 2-(Optionally substituted)phenyl-5 or 6-substituted benzoxazoles |
-
1984
- 1984-10-22 IT IT23264/84A patent/IT1177017B/it active
-
1985
- 1985-10-07 EP EP85112699A patent/EP0182061B1/en not_active Expired - Lifetime
- 1985-10-07 DE DE8585112699T patent/DE3585022D1/de not_active Expired - Fee Related
- 1985-10-07 US US06/784,892 patent/US4652654A/en not_active Expired - Lifetime
- 1985-10-07 AT AT85112699T patent/ATE70832T1/de not_active IP Right Cessation
- 1985-10-18 JP JP60231423A patent/JPS61100574A/ja active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0368026B2 (cs) | 1991-10-25 |
| ATE70832T1 (de) | 1992-01-15 |
| US4652654A (en) | 1987-03-24 |
| EP0182061A1 (en) | 1986-05-28 |
| IT8423264A0 (it) | 1984-10-22 |
| DE3585022D1 (de) | 1992-02-06 |
| JPS61100574A (ja) | 1986-05-19 |
| IT8423264A1 (it) | 1986-04-22 |
| IT1177017B (it) | 1987-08-26 |
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