AT286971B - Process for the preparation of new N-substituted 2-phenyl-2- (2'-hydroxy-1'-naphthyl) -ethylamines and their acid addition salts - Google Patents
Process for the preparation of new N-substituted 2-phenyl-2- (2'-hydroxy-1'-naphthyl) -ethylamines and their acid addition saltsInfo
- Publication number
- AT286971B AT286971B AT1088869A AT1088869A AT286971B AT 286971 B AT286971 B AT 286971B AT 1088869 A AT1088869 A AT 1088869A AT 1088869 A AT1088869 A AT 1088869A AT 286971 B AT286971 B AT 286971B
- Authority
- AT
- Austria
- Prior art keywords
- hydroxy
- acid addition
- preparation
- naphthyl
- phenyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 7
- 239000002253 acid Substances 0.000 title description 8
- 150000003839 salts Chemical class 0.000 title description 7
- 238000002360 preparation method Methods 0.000 title description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 230000002378 acidificating effect Effects 0.000 claims description 3
- 239000003638 chemical reducing agent Substances 0.000 claims description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims 2
- 229910052987 metal hydride Inorganic materials 0.000 claims 1
- 150000004681 metal hydrides Chemical class 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
- 150000007524 organic acids Chemical class 0.000 description 5
- 229940095064 tartrate Drugs 0.000 description 5
- 125000003545 alkoxy group Chemical group 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 150000002431 hydrogen Chemical class 0.000 description 3
- 150000002466 imines Chemical class 0.000 description 3
- 239000012442 inert solvent Substances 0.000 description 3
- -1 methoxy, ethoxy, propoxy Chemical group 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- UCTWMZQNUQWSLP-UHFFFAOYSA-N adrenaline Chemical compound CNCC(O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-UHFFFAOYSA-N 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 241000208011 Digitalis Species 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- YZCKVEUIGOORGS-IGMARMGPSA-N Protium Chemical compound [1H] YZCKVEUIGOORGS-IGMARMGPSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 230000002763 arrhythmic effect Effects 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 229940097217 cardiac glycoside Drugs 0.000 description 1
- 239000002368 cardiac glycoside Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 150000003947 ethylamines Chemical class 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 208000021822 hypotensive Diseases 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- LPMXVESGRSUGHW-HBYQJFLCSA-N ouabain Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@@H]1C[C@@]2(O)CC[C@H]3[C@@]4(O)CC[C@H](C=5COC(=O)C=5)[C@@]4(C)C[C@@H](O)[C@@H]3[C@@]2(CO)[C@H](O)C1 LPMXVESGRSUGHW-HBYQJFLCSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229930002534 steroid glycoside Natural products 0.000 description 1
- 150000008143 steroidal glycosides Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
<Desc/Clms Page number 1>
Verfahren zur Herstellung von neuen N-substituierten 2-Phenyl-2- (2' -l1ydroxy-l'-naphthyl) -äthylaminen und deren Säureadditionssalzen
Die Erfindung betrifft ein Verfahren zur Herstellung von neuen N-substituierten 2-Phenyl-2- (2 r -hy- droxy-1'-naphthyl)-âthylaminen der allgemeinen Formel
EMI1.1
in der W Wasserstoff oder Hydroxy, X und Y unabhängig voneinander jeweils Wasserstoff, Hydroxy oder Niedrigalkoxy und R4 und Rs unabhängig voneinander Wasserstoff oder Methyl bedeuten, und deren Säureadditionssalzen mit anorganischen oder organischen Säuren. Diese Verbindungen der Formel 1 besitzen die Fähigkeit Unregelmässigkeiten im Rhythmus des Herzschlages zu normalisieren und sind deshalb geeignet, eine Normalisierung bei verschiedenen Arrhythmiezuständen herbeizuführen.
Ausserdem weisen diese Verbindungen auch hypotensive und lokalanästhetische Eigenschaften auf. Die bei den Verbindungen der allgemeinen Formel I festgestellten pharmakologischen Eigenschaften zeigen an, dass sie besonders nützlich sind bei der Behandlung primärer Arrhythmien, sowohl derjenigen, die durch Medikamente hervorgerufen werden, beispielsweise auf Grund einer Überdosis von Adrenalin oder Herzglykosiden, wie z. B. Digitalis oder Quabain, als auch derjenigen, die bei bestimmten Herzkrankheiten auftreten.
Der verwendete Ausdruck"Niedrigaikoxy"bedeutet Aikoxygruppen, die nicht mehr als B Kohlenstoffatome enthalten, demnach Methoxy-, Äthoxy-, Propoxy- und Isopropoxygruppen.
Die Verbindungen der Formel I und ihre Säureadditionssalze mit anorganischen oder organischen Säuren werden hergestellt, indem man eine Verbindung der allgemeinen Formel
<Desc/Clms Page number 2>
EMI2.1
in der W, X, Y, R4 und Rs die oben angegebenen Bedeutungen besitzen, in einem inerten Lösungsmittel reduziert und, gewünschtenfalls, das erhaltene Produkt in ein Säureadditionssalz mit einer anorganischen oder einer organischen Säure umwandelt.
Die zweckmässigerweise für die Reduktion der Imine der Formel II verwendeten Reduktionsmittel sind katalytisch aktivierter Wasserstoff oder hydridliefernde Agentien. Das Hydrierungsverfahren wird vorteilhaft in niedrigalkanolischer Lösung durchgeführt, beispielsweise in Methanol, Äthanol, Propanol oder Isopropanol, bei erhöhten Drücken (bis zu 50 at), gegebenenfalls bei erhöhten Temperaturen.
Dieses Verfahren ist von besonderem Wert für die Herstellung von Verbindungen der Formel I, in der X und Y unabhängig voneinander einenWasserstoff-, Hydroxy-oderMethoxyrest und R4 und Rs einen Wasserstoffrest bedeuten. Des weiteren können Imine der Formel II durch hydridliefernde Agentien, beispielsweise Diboran oder Lithiumaluminiumhydrid, in einem ätherähnlichen Lösungsmittel, beispielsweise Diäthyläther oder Tetrahydrofuran, oder durch ein Alkaliborhydrid, wie z. B. Natriumborhydrid, in einem niedrigalkanolischen Lösungsmittel reduziert werden.
Die Imine der Formel II können aus einem Amin der allgemeinen Formel
EMI2.2
in der W, X und Y die in der Formel I angegebenen Bedeutungen besitzen, hergestellt werden, indem man dieses mit einer Verbindung der allgemeinen Formel
EMI2.3
in der R 4 und R5 die in der Formel Il angegebene Bedeutung besitzen, gegebenenfalls in Gegenwart katalytischer Mengen einer starken Säure, umsetzt, wobei die Umsetzung in einem inerten Lösungmittel durchgeführt wird.
Geeignete Lösungsmittel sind niedere Alkanole, beispielsweise Äthanol, und geeignete saure Kondensationsmittel sind beispielsweise Chlorwasserstoffsäure oder p-Toluolsulfonsäure. Die Kondensation der Amine der Formel III mit den Carbonylverbindungen der Formel IV wird vorteilhaft bei der Rückflusstemperatur durchgeführt.
<Desc/Clms Page number 3>
EMI3.1
<Desc/Clms Page number 4>
eingestellt. Dann wurde die Lösung durch Zugabe von Chlorwasserstoffsäure stark sauer gemacht, und das sich ausscheidende d-Aminhydrochlorid wurde gesammelt. Die Umkristallisation aus Äthanol/Äther ergab weisse Kristalle, F. 2490, [ct] D = +52, 20 (c = 1, 045 in CHgOH).
Die Mutterlaugen und Rückstände aus den obigen fraktionierten Extraktionen und Kristallisationen bestanden aus Amintartraten, die mit 1-Amin-l-tartrat angereichert waren. Dieses Material wurde durch Zugabe von wässerigem Natriumhydroxyd in die (mit l-Amin angereicherte) freie Base und dann in das angereicherte 1-Amin-d-tartrat umgewandelt. 15, 8 g dieses angereicherten 1-Amin-d-tartrats wurde in einem heissen Extraktor wie oben beschrieben aus Aceton umkristallisiert, bis reines 1-Amin-d-tartrat, [ct] D = - 60, 70 (c = 0, 961 in CHPH) erhalten wurde.
5 g des reinen 1-Amin-d-tartrats in 300 ml Wasser wurden mit 22 ml ln-wässerigem Natriumhydroxyd und dann mit 30 ml 1n- Chlorwasserstoffsäure behandelt. Aus der Lösung fielen beim Kühlen 3, 4 g reines 1-Aminhydrochlorid in Form cremefarbiger Plättchen aus, F. 2500, [ct] D = -53, 90 (c = 1, 100 in Cl\OH).
PAT ENTANSPRÜCHE
1. Verfahren zur Herstellung von neuen N-substituierten 2-Phenyl-2- (2'-hydroxy-l'-naphthyl)- - Nthylaminen der allgemeinen Formel
EMI4.1
in der W Wasserstoff oder Hydroxy, X und Y unabhängig voneinander Wasserstoff, Hydroxy oder Niedrigalkoxy und R4 und Rs unabhängig voneinander Wasserstoff oder Methyl bedeuten, und deren Säureadditionssalzen mit einer anorganischen oder organischen Säure, dadurch gekennzeichnet, dass man eine Verbindung der allgemeinen Formel
EMI4.2
in der W, X, Y, R4 und Rs die oben angegebenen Bedeutungen besitzen, in einem inerten Lösungsmittel reduziert und, gewünschtenfalls, das erhaltene Produkt in ein Säureadditionssalz mit einer anorganischen oder einer organischen Säure umwandelt.
<Desc / Clms Page number 1>
Process for the preparation of new N-substituted 2-phenyl-2- (2'-l1ydroxy-l'-naphthyl) ethylamines and their acid addition salts
The invention relates to a process for the preparation of new N-substituted 2-phenyl-2- (2 r -hydroxy-1'-naphthyl) -âthylamines of the general formula
EMI1.1
in which W is hydrogen or hydroxy, X and Y, independently of one another, are each hydrogen, hydroxy or lower alkoxy and R4 and Rs are, independently of one another, hydrogen or methyl, and their acid addition salts with inorganic or organic acids. These compounds of formula 1 have the ability to normalize irregularities in the rhythm of the heartbeat and are therefore suitable for bringing about a normalization in various arrhythmic states.
In addition, these compounds also have hypotensive and local anesthetic properties. The pharmacological properties found in the compounds of general formula I indicate that they are particularly useful in the treatment of primary arrhythmias, both those caused by drugs, for example due to an overdose of adrenaline or cardiac glycosides, such as. B. Digitalis or Quabain, as well as those that occur with certain heart diseases.
The term "lower alkoxy" used denotes alkoxy groups which contain no more than B carbon atoms, hence methoxy, ethoxy, propoxy and isopropoxy groups.
The compounds of the formula I and their acid addition salts with inorganic or organic acids are prepared by adding a compound of the general formula
<Desc / Clms Page number 2>
EMI2.1
in which W, X, Y, R4 and Rs have the meanings given above, reduced in an inert solvent and, if desired, converting the product obtained into an acid addition salt with an inorganic or an organic acid.
The reducing agents expediently used for the reduction of the imines of the formula II are catalytically activated hydrogen or hydride-supplying agents. The hydrogenation process is advantageously carried out in a low-alkanol solution, for example in methanol, ethanol, propanol or isopropanol, at elevated pressures (up to 50 atmospheres), if appropriate at elevated temperatures.
This process is of particular value for the preparation of compounds of the formula I in which X and Y, independently of one another, represent a hydrogen, hydroxy or methoxy radical and R4 and Rs represent a hydrogen radical. Furthermore, imines of the formula II can be prepared by hydride-supplying agents, for example diborane or lithium aluminum hydride, in an ether-like solvent, for example diethyl ether or tetrahydrofuran, or by an alkali borohydride, such as. B. sodium borohydride, are reduced in a low alkanol solvent.
The imines of the formula II can be prepared from an amine of the general formula
EMI2.2
in which W, X and Y have the meanings given in formula I, are prepared by reacting this with a compound of the general formula
EMI2.3
in which R 4 and R 5 have the meaning given in formula II, optionally in the presence of catalytic amounts of a strong acid, the reaction being carried out in an inert solvent.
Suitable solvents are lower alkanols, for example ethanol, and suitable acidic condensing agents are, for example, hydrochloric acid or p-toluenesulfonic acid. The condensation of the amines of the formula III with the carbonyl compounds of the formula IV is advantageously carried out at the reflux temperature.
<Desc / Clms Page number 3>
EMI3.1
<Desc / Clms Page number 4>
set. Then the solution was made strongly acidic by the addition of hydrochloric acid and the precipitating α-amine hydrochloride was collected. Recrystallization from ethanol / ether gave white crystals, mp 2490, [ct] D = +52.20 (c = 1.045 in CHgOH).
The mother liquors and residues from the above fractional extractions and crystallizations consisted of amine tartrates which were enriched with 1-amine-1-tartrate. This material was converted to the free base (enriched in 1-amine) and then to the enriched 1-amine-d-tartrate by the addition of aqueous sodium hydroxide. 15.8 g of this enriched 1-amine-d-tartrate were recrystallized from acetone in a hot extractor as described above until pure 1-amine-d-tartrate, [ct] D = -60.70 (c = 0.961 in CHPH).
5 g of the pure 1-amine-d-tartrate in 300 ml of water were treated with 22 ml of 1N aqueous sodium hydroxide and then with 30 ml of 1N hydrochloric acid. On cooling, 3.4 g of pure 1-amine hydrochloride precipitated from the solution in the form of cream-colored platelets, F. 2500, [ct] D = -53.90 (c = 1.100 in Cl \ OH).
PAT DISCLAIMER
1. Process for the preparation of new N-substituted 2-phenyl-2- (2'-hydroxy-l'-naphthyl) - - Nthylamines of the general formula
EMI4.1
in which W is hydrogen or hydroxy, X and Y are independently hydrogen, hydroxy or lower alkoxy and R4 and Rs are independently hydrogen or methyl, and their acid addition salts with an inorganic or organic acid, characterized in that a compound of the general formula
EMI4.2
in which W, X, Y, R4 and Rs have the meanings given above, reduced in an inert solvent and, if desired, converting the product obtained into an acid addition salt with an inorganic or an organic acid.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AT1088869A AT286971B (en) | 1968-07-18 | 1968-07-18 | Process for the preparation of new N-substituted 2-phenyl-2- (2'-hydroxy-1'-naphthyl) -ethylamines and their acid addition salts |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AT1088869A AT286971B (en) | 1968-07-18 | 1968-07-18 | Process for the preparation of new N-substituted 2-phenyl-2- (2'-hydroxy-1'-naphthyl) -ethylamines and their acid addition salts |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AT286971B true AT286971B (en) | 1971-01-11 |
Family
ID=3625354
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AT1088869A AT286971B (en) | 1968-07-18 | 1968-07-18 | Process for the preparation of new N-substituted 2-phenyl-2- (2'-hydroxy-1'-naphthyl) -ethylamines and their acid addition salts |
Country Status (1)
| Country | Link |
|---|---|
| AT (1) | AT286971B (en) |
-
1968
- 1968-07-18 AT AT1088869A patent/AT286971B/en not_active IP Right Cessation
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE1795841C3 (en) | H2'-chloro) -benzyl-2-di-sec.-butylamino-acetyl-pyrrole, its salts and process for their preparation | |
| CH506525A (en) | Aromatic ethers | |
| DE2227022C2 (en) | Hexamethylenediamine compounds and their use | |
| DE2351281C3 (en) | Aminophenylethanolamine derivatives, their production and use | |
| DE916168C (en) | Process for the preparation of pyrrolidinoalkylphenothiazines | |
| DE2616484C3 (en) | Basic benzoyl ethers, their salts and quaternary ammonium compounds as well as processes for their preparation and pharmaceuticals containing them | |
| AT281009B (en) | Process for the preparation of new N- [2-phenyl-2- (2'-hydroxy-1'-naphthyl) ethyl] isopropylamines and their acid addition salts | |
| AT201604B (en) | Process for the preparation of new 1-aza- [2,3: 5,6] -dibenzocycloheptadiene derivatives, their acid salts and quaternary salts | |
| AT237599B (en) | Process for the production of new amines and their acid addition salts | |
| AT244933B (en) | Process for the preparation of new 1, 5-diphenyl-3-azapentanolen- (1) and their acid addition salts | |
| AT332378B (en) | PROCESS FOR THE PREPARATION OF NEW N- (3,3-DIPHENYLPROPYL) -PROPYLENEDIAMINES AND THEIR ACID ADDITIONAL SALTS | |
| AT206890B (en) | Process for the preparation of new tertiary amines | |
| AT243270B (en) | Process for the preparation of piperazine derivatives | |
| AT226690B (en) | Process for the preparation of new 1-R-2,5-bis-halomethyl-pyrrolidines and of acid addition salts and quaternary ammonium compounds thereof | |
| AT210435B (en) | Process for the production of new ferrocene derivatives | |
| DE2302000C3 (en) | 2-Hydroxy-2-phenylethylamines, their acid addition salts, process for their production and medicinal products | |
| AT334883B (en) | PROCESS FOR PRODUCING NEW ALFA (1-BIS-ARYLALKYLAMINOALKYL) ARALCOXYBENZYL ALCOHOLS | |
| DE1242241B (en) | Process for the preparation of substituted phenyl-alpha-aminoketones and their acid addition salts or their optical antipodes | |
| AT230364B (en) | Process for the preparation of 9,10-dihydroanthracenes and their acid addition salts | |
| AT264527B (en) | Process for the preparation of new N-substituted 1-phenyl-2-aminopropanes and their acid addition salts | |
| AT201588B (en) | Process for the preparation of new aryloxyacetic acid amides | |
| AT254182B (en) | Process for the preparation of new substituted benzamides and their acid addition salts | |
| DE1018869B (en) | Process for the preparation of aminoalkyl purine derivatives | |
| AT209901B (en) | Process for the preparation of new tertiary amines | |
| AT222643B (en) | Process for the preparation of new aryloxyacetic acid amides |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EIH | Change in the person of patent owner | ||
| ELJ | Ceased due to non-payment of the annual fee |