DK150822B - Framgangsmaade til fremstilling af cis-2-phenyl-bicyclooctylaminer - Google Patents
Framgangsmaade til fremstilling af cis-2-phenyl-bicyclooctylaminer Download PDFInfo
- Publication number
- DK150822B DK150822B DK294079AA DK294079A DK150822B DK 150822 B DK150822 B DK 150822B DK 294079A A DK294079A A DK 294079AA DK 294079 A DK294079 A DK 294079A DK 150822 B DK150822 B DK 150822B
- Authority
- DK
- Denmark
- Prior art keywords
- reaction
- phenyl
- cis
- oil
- bicyclooctylamines
- Prior art date
Links
- 238000000034 method Methods 0.000 title description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
- 229910052739 hydrogen Inorganic materials 0.000 description 7
- 239000001257 hydrogen Substances 0.000 description 7
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- MGNZXYYWBUKAII-UHFFFAOYSA-N cyclohexa-1,3-diene Chemical compound C1CC=CC=C1 MGNZXYYWBUKAII-UHFFFAOYSA-N 0.000 description 4
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 150000002081 enamines Chemical class 0.000 description 3
- 239000012259 ether extract Substances 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
- 239000002808 molecular sieve Substances 0.000 description 3
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000000935 antidepressant agent Substances 0.000 description 2
- 229940005513 antidepressants Drugs 0.000 description 2
- 239000006286 aqueous extract Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 2
- 229910003446 platinum oxide Inorganic materials 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 1
- 238000005698 Diels-Alder reaction Methods 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 238000006828 Rosenmund reduction reaction Methods 0.000 description 1
- YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000012320 chlorinating reagent Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cis-cyclohexene Natural products C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000012024 dehydrating agents Substances 0.000 description 1
- 230000003001 depressive effect Effects 0.000 description 1
- 125000005265 dialkylamine group Chemical group 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
- -1 less than 15% Chemical compound 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/68—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton
- C07C209/70—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton by reduction of unsaturated amines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
- C07C211/26—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring
- C07C211/29—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by halogen atoms or by nitro or nitroso groups
-
- 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
- C07C2602/00—Systems containing two condensed rings
- C07C2602/36—Systems containing two condensed rings the rings having more than two atoms in common
- C07C2602/44—Systems containing two condensed rings the rings having more than two atoms in common the bicyclo ring system containing eight carbon atoms
Description
150822
Den foreliggende opfindelse angår en særlig fremgangsmåde til fremstilling af cis-2-phenyl-bicyclooctylaminer.
I vesttysk offentliggørelsesskrift nr. 2.619.617 beskrives en kategori cis-bicyclooctylamin-derivater, som besidder 05 antidepressiv aktivitet, og som derfor er nyttige ved behandling af forskellige depressive tilstande hos pattedyr. Det har vist sig, at forbindelser med formlen (I): /f\ M ch2nr1r2 1° \\r* (I) . \ L*Ar 1 2 hvori R og R betegner C1_3 alkyl, og Ar betegner en phenyl-15 gruppe, som eventuelt er substitueret med op til to halogenatomer, og deres farmaceutisk acceptable salte, er særligt lovende antidepressive midler. Særlig aktiv er forbindelsen cis- 2-(3,4-dichlorphenyl)-3-N,N-dimethylamino-bicyclo[2.2.2]octan.
De i ovennævnte offentliggørelsesskrift beskrevne syn-20 tesemetoder til fremstilling af forbindelser med formlen (I) indebærer en flertrins-fremgangsmåde, som er temmelig besværlig. Det samme gælder den fra DK patentansøgning nr. 2028/76 (DK-B 147.577) kendte syntesemetode. Nærværende fremgangsmåde gør det muligt at fremstille forbindelser med formlen (I) ud 25 fra lettilgængelige udgangsmaterialer på en simpel og elegant måde.
Ifølge den foreliggende opfindelse tilvejebringes der en særlig fremgangsmåde til fremstilling af cis-2-phenyl-bicyclo-octylaminer med formlen (I), hvilken fremgangsmåde er ejen-50 dommelig ved, at en forbindelse med formlen (II):
H
3 ~ 1 1 2 R \/f\y C-NR^R* \ (II)
” ,.aK
2 150822 12 . 3 hvori R , R og Ar har den ovenfor anførte betydning, og R og 4 R betegner hydrogen eller tilsammen repræsenterer en enkelt-binding, reduceres katalytisk med hydrogen og Pt02.
Reaktionstemperaturer fra -20°C til 100°C, f.eks. fra 0°C 05 til 100°C, kan anvendes til gennemførelse af omsætningén, som normalt er fuldstændig inden for 24 timer. Naturligvis er det, "34 ...
nar R og R sammen repræsenterer en kemisk binding, nødvendigt med et ekstra mol hydrogen for at fuldføre reduktionen. Den anvendte katalysator er Pt02 (Adams-katalysator), 10 som når den anvendes i forbindelse med et polært organisk opløsningsmiddel, såsom en alkanol, f.eks. methanol, ethanol og isopropanol, eller ethylacetat, muliggør fremstilling af rene cis-forbindelser med formlen (I), kun kontamineret med små mængder af den tilsvarende trans-isomer, dvs. mindre end 15%, 15 og oftest mindre end 5%.
Forbindelserne med formlen (II) er hidtil ukendte. Fremstillingen af disse forbindelser ud fra lettilgængelige udgangsmaterialer kan illustreres ved følgende reaktionsskema: 3 150822 H C00H Η CHO (IV) c — c _Lål-^ c=c
AlA Αί Ar ^ (b)| 1(c) 05
Η x / COC1 / Y
\>l
.. “ I
1 A Ύ iifY°cl (a) rfYH0 XAv ' . \Ar
Xid)h (d) 15 Γ^\Γ ^ k/Au.
H
20 ~”Nr1r2 AC ^ 25 Reaktion (a) er en reduktion, som kan gennemføres via det tilsvarende syrechlorid under anvendelse af konventionelle Rosenmund-reduktionsbetingelser og -reagenser.
Chloreringsreaktionen (b) kan gennemføres under anvendelse af konventionelle chloreringsmidler, såsom thionylchlorid 30 eller oxalylchlorid.
Reaktion (c) indebærer en Diels-Alder reaktion med en 1,3-cyclohexadien ved en temperatur mellem 100 og 150°C. Syre-chloridet med formlen (V) reagerer hurtigere med cyclohexadie-nen end aldehydet med formlen (IV).
35 For at udvirke dannelsen af enaminen ved reaktion (d) er det nødvendigt at omsætte aldehydet med den tilsvarende dial-kylamin i nærværelse af et egnet dehydreringsmiddel, såsom ti- 4 150822 tantetrachlorid, molekylsigter (3A) eller vandfri kaliumcarbo-nat.
Reaktion (e) er en katalytisk hydrogenering, som kan gennemføres under anvendelse af hydrogen og en palladium-på-05 trækul katalysator i et inert opløsningsmiddel såsom ethyl-acetat.
Opfindelsen illustreres yderligere under henvisning til de efterfølgende eksempler.
10 Eksempel 1 (Fremstilling af udgangsforbindelse) 2-(3,4-dichlorphenyl)-bicyclo[2.2.2]octan-3-N, N-dimethyl amino-yliden (a) Til trans-2-(3,4-dichlorphenyl)-3-formylbicyclo-[2.2.2]-15 octan (2 g, 7,1 mmol) og dimethylamin (5 ml) i benzen (35 ml) sattes dråbevis titantetrachlorid (0,67 g, 3,5 mmol) i benzen (15 ml), idet temperaturen blev holdt mellem 0 og 10°C.
Reaktionsblandingen henstod ved stuetemperatur natten over, filtreredes, og overskydende opløsningsmiddel afdampe-20 des, hvilket gav det i overskriften nævnte produkt i form af et hvidt olieagtigt fast stof (udbytte 2,5 g). Produktets struktur bekræftedes ved dets NMR-, IR- og massespektre. Destillation af produktet kunne udføres ved 180°C/0,03 mm.
25 (b) En blanding af trans-2-(3,4-dichlorphenyl)-3-formylbicy- clo[2.2.2]octan (1 g), molekylsigte type 3A (2 g pulver), dimethylamin (1 ml) og benzen (10 ml) omrørtes ved stuetemperatur i 16 timer. Reaktionsblandingen filtreredes, og opløsningsmiddel afdampedes, hvilket gav det i overskriften nævnte 30 produkt i form af et hvidt fast stof (udbytte 1,2 g), som snart transformeredes til en olie, kogepunkt 180°C ved 0,03 mm. Strukturen bekræftedes igen ved NMR-, IR- og massespektre.
35 150822 5
Eksempel 2 cis-2-(3,4-Dichlorphenyl)-3-N,N-dimethylaminomethyl-bicyclo- [2.2,2]octan 05 Platinoxid (106,8 mg) hydrogeneredes ved stuetemperatur i isopropanol (3 ml). Hydrogenoptagelsen var efter 20 minutters forløb 21,8 ml (teoretisk 21,15 ml). Enaminproduktet fra eksempel 1 (189 mg) i isopropanol (2 ml) tilsattes dernæst, og blandingen hydrogeneredes i 45 minutter. Hydrogenoptagelsen 10 var 14,8 ml (teoretisk 13,7 ml). Katalysatoren frafiltreredes, og filtratet inddampedes til en olie (udbytte 153 mg, 81%). Denne olie opløstes i 5 n saltsyre og ekstraheredes med ether. Etherekstrakten vaskedes med vand, tørredes over magnesiumsulfat og inddampedes til opnåelse af en olie (udbytte 70,7 mg, 15 37%), idet neutrale bestanddele, som dannedes under reaktio nen, således fjernedes. Den sure vandige ekstrakt gjordes basisk med 5 n NaOH og ekstraheredes med ether. Etheren vaskedes med vand, tørredes over vandfri magnesiumsulfat og inddampedes til opnåelse af det i overskriften nævnte produkt i form af en 20 olie (udbytte 72,9 mg, 38,5%).
Strukturen bekræftedes ved NMR og GLC. Disse analysemetoder viste, at reaktionsproduktet var rent cis-materiale (98%) med kun små mængder (2%) trans-materiale som urenhed.
25 Eksempel 3 (Fremstilling af udgangsforbindelse) 2-(3,4-Dichlorphenyl)-bicyclo[2.2.2]oct-5-en-3-N,N-dimethyl-aminoyliden trans-2-(3,4-Dichlorphenyl)-3-formylbicyclo[2.2.2]-oct-5-30 en (0,26 g, 0,9 mmol), molekylsigter (type 3A pulver, 0,52), dimethylamin (0,3 ml) og benzen (5 ml) omrørtes i 4 dage. Sigterne frafiltreredes, og filtratet inddampedes til opnåelse af det i overskriften nævnte produkt i form af en gul olie (udbytte 0,27 g). Strukturen bekræftedes ved NMR- og IR-spektral-35 data.
150822 6
Eksempel 4 cis-2-(3,4-Dichlorphenyl )-3-N,N-dimethylaminomethyl-bicyclo-[2.2.21octan 05 Platinoxid (108 mg) hydrogeneredes ved atmosfærisk tryk i benzen (3 ml) ved stuetemperatur i løbet af en time. Benzen (25 ml) tilsattes dernæst, og blandingen tilbagesvaledes under anvendelse af et Dean og Stark apparat. Efter 2 timers forløb vaskedes katalysatoren tre gange med ethanol (30 ml), og efter 10 tilsætning af ethanol (3 ml) hydrogeneredes katalysatoren i en time. Enaminen fra eksempel 3 (235 mg) i ethanol (2 ml) indsprøjtedes i apparatet, og blandingen hydrogeneredes. Efter 3 timers forløb var hydrogenoptagelsen 33,1 ml (teoretisk 34,1 ml). Katalysatoren frafiltreredes, og filtratet inddampedes 15 til opnåelse af en olie. Denne opløstes i 5 n HC1 og ekstra-heredes med ether. Etherekstrakten vaskedes, tørredes og inddampedes til opnåelse af en olie (101,5 mg), som indeholdt ikke-basiske produkter. De sure vandige ekstrakter gjordes basiske (5 n NaOH) og ekstraheredes med ether. Etherekstrakterne 20 vaskedes, tørredes og inddampedes til opnåelse af en olie (90 mg, 38,3%). NMR-, GLC- og MS-analyser viste, at denne olie var en blanding af 86% cis- og 14% trans-isomer.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB7829988 | 1978-07-15 | ||
| GB7829988 | 1978-07-15 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DK294079A DK294079A (da) | 1980-01-16 |
| DK150822B true DK150822B (da) | 1987-06-29 |
| DK150822C DK150822C (da) | 1988-01-25 |
Family
ID=10498451
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK294079A DK150822C (da) | 1978-07-15 | 1979-07-12 | Framgangsmaade til fremstilling af cis-2-phenyl-bicyclooctylaminer |
Country Status (31)
| Country | Link |
|---|---|
| US (1) | US4215074A (da) |
| EP (1) | EP0008163B1 (da) |
| JP (1) | JPS5515476A (da) |
| KR (1) | KR820000628B1 (da) |
| AR (1) | AR221885A1 (da) |
| AT (1) | AT366661B (da) |
| AU (1) | AU530973B2 (da) |
| BE (1) | BE877674A (da) |
| CA (1) | CA1131253A (da) |
| CH (1) | CH640821A5 (da) |
| CS (1) | CS215118B2 (da) |
| DD (1) | DD144913A5 (da) |
| DE (1) | DE2966182D1 (da) |
| DK (1) | DK150822C (da) |
| EG (1) | EG14307A (da) |
| ES (1) | ES482462A1 (da) |
| FI (1) | FI65230C (da) |
| FR (1) | FR2430931A1 (da) |
| GR (1) | GR69639B (da) |
| HU (1) | HU181902B (da) |
| IE (1) | IE48773B1 (da) |
| IL (1) | IL57779A (da) |
| LU (1) | LU81498A1 (da) |
| MX (1) | MX5510E (da) |
| NZ (1) | NZ190991A (da) |
| PH (1) | PH15975A (da) |
| PL (1) | PL119592B1 (da) |
| PT (1) | PT69908A (da) |
| RO (1) | RO78312A (da) |
| YU (1) | YU169879A (da) |
| ZA (1) | ZA793518B (da) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4019782A1 (de) * | 1990-06-21 | 1992-01-02 | Basf Ag | 9-amino-2-phenylbicyclo (3.3.1.) und 9-amino-2-phenylbicyclo (3.3.1.) non-2-ene und diese enthaltende therapeutische mittel |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AT219020B (de) * | 1959-08-01 | 1962-01-10 | Merck Ag E | Verfahren zur Herstellung von neuen N-substituierten Amino-norcamphanderivaten sowie deren Säureadditionssalzen und quaternären Ammoniumverbindungen |
| US3148118A (en) * | 1962-06-05 | 1964-09-08 | Thesing Jan | Analeptically active agents |
| US3228984A (en) * | 1963-11-04 | 1966-01-11 | American Home Prod | 1, 4-bis-cyclic and aryl-amino-[2.2.2] bicyclooctane derivatives |
| US3264351A (en) * | 1964-07-08 | 1966-08-02 | American Home Prod | 1, 4-diaminobicyclo [2.2.2] octanes |
| US3515740A (en) * | 1967-02-20 | 1970-06-02 | Orville D Frampton | Cyano cyclohexenyl compounds |
| GB1444717A (en) * | 1972-11-04 | 1976-08-04 | Lilly Industries Ltd | Bicycloalkyl derivatives |
| GB1549174A (en) * | 1975-05-08 | 1979-08-01 | Lilly Industries Ltd | Amine derivatives |
| AT345781B (de) * | 1975-05-08 | 1978-10-10 | Lilly Industries Ltd | Verfahren zur herstellung von neuen 3- aminomethyl-2-phenylbicyclo (2,2,2) octanen und -octenen sowie deren saeureadditionssalzen |
-
1979
- 1979-06-18 US US06/049,672 patent/US4215074A/en not_active Expired - Lifetime
- 1979-07-11 MX MX798175U patent/MX5510E/es unknown
- 1979-07-11 AT AT0484179A patent/AT366661B/de not_active IP Right Cessation
- 1979-07-11 EP EP79301355A patent/EP0008163B1/en not_active Expired
- 1979-07-11 HU HU79LI345A patent/HU181902B/hu unknown
- 1979-07-11 AR AR277250A patent/AR221885A1/es active
- 1979-07-11 FR FR7917993A patent/FR2430931A1/fr active Granted
- 1979-07-11 DE DE7979301355T patent/DE2966182D1/de not_active Expired
- 1979-07-12 ZA ZA00793518A patent/ZA793518B/xx unknown
- 1979-07-12 FI FI792192A patent/FI65230C/fi not_active IP Right Cessation
- 1979-07-12 NZ NZ190991A patent/NZ190991A/xx unknown
- 1979-07-12 BE BE6/46891A patent/BE877674A/fr not_active IP Right Cessation
- 1979-07-12 DK DK294079A patent/DK150822C/da not_active IP Right Cessation
- 1979-07-12 PT PT69908A patent/PT69908A/pt unknown
- 1979-07-12 RO RO7998139A patent/RO78312A/ro unknown
- 1979-07-12 GR GR59591A patent/GR69639B/el unknown
- 1979-07-12 AU AU48887/79A patent/AU530973B2/en not_active Ceased
- 1979-07-12 JP JP8865979A patent/JPS5515476A/ja active Pending
- 1979-07-12 YU YU01698/79A patent/YU169879A/xx unknown
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- 1979-07-13 CA CA331,752A patent/CA1131253A/en not_active Expired
- 1979-07-13 LU LU81498A patent/LU81498A1/fr unknown
- 1979-07-13 DD DD79214325A patent/DD144913A5/de unknown
- 1979-07-13 PH PH22779A patent/PH15975A/en unknown
- 1979-07-13 ES ES482462A patent/ES482462A1/es not_active Expired
- 1979-07-13 CS CS794935A patent/CS215118B2/cs unknown
- 1979-07-13 CH CH654979A patent/CH640821A5/fr not_active IP Right Cessation
- 1979-07-14 PL PL1979217118A patent/PL119592B1/pl unknown
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- 1979-07-16 KR KR7902369A patent/KR820000628B1/ko active
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| Date | Code | Title | Description |
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| PBP | Patent lapsed |