AT222655B - Process for the preparation of new derivatives of 5H-dibenzo [b, f] azepines or their salts or quaternary ammonium compounds - Google Patents
Process for the preparation of new derivatives of 5H-dibenzo [b, f] azepines or their salts or quaternary ammonium compoundsInfo
- Publication number
- AT222655B AT222655B AT851060A AT851060A AT222655B AT 222655 B AT222655 B AT 222655B AT 851060 A AT851060 A AT 851060A AT 851060 A AT851060 A AT 851060A AT 222655 B AT222655 B AT 222655B
- Authority
- AT
- Austria
- Prior art keywords
- dibenzo
- molecular weight
- low molecular
- azepines
- salts
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 4
- 238000002360 preparation method Methods 0.000 title claims description 4
- 150000003839 salts Chemical class 0.000 title claims description 3
- LCGTWRLJTMHIQZ-UHFFFAOYSA-N 5H-dibenzo[b,f]azepine Chemical class C1=CC2=CC=CC=C2NC2=CC=CC=C21 LCGTWRLJTMHIQZ-UHFFFAOYSA-N 0.000 title claims 2
- 150000003856 quaternary ammonium compounds Chemical class 0.000 title claims 2
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000002947 alkylene group Chemical group 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 1
- 125000001931 aliphatic group Chemical group 0.000 claims 1
- 150000007522 mineralic acids Chemical class 0.000 claims 1
- 150000007524 organic acids Chemical class 0.000 claims 1
- 235000005985 organic acids Nutrition 0.000 claims 1
- 150000001538 azepines Chemical class 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- -1 5- (γ-dimethylamino-propyl) -10-methoxy-3,7-dichloro-5H-dibenzo [b, f] azepine Chemical compound 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- VSZGCLXGCOECAY-UHFFFAOYSA-N 6,11-dihydrobenzo[b][1]benzazepin-5-one Chemical compound O=C1CC2=CC=CC=C2NC2=CC=CC=C12 VSZGCLXGCOECAY-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 125000005277 alkyl imino group Chemical group 0.000 description 1
- 150000001414 amino alcohols Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 230000003474 anti-emetic effect Effects 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 239000002111 antiemetic agent Substances 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- UZVGSSNIUNSOFA-UHFFFAOYSA-N dibenzofuran-1-carboxylic acid Chemical compound O1C2=CC=CC=C2C2=C1C=CC=C2C(=O)O UZVGSSNIUNSOFA-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000002005 ganglioplegic effect Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000004081 narcotic agent Substances 0.000 description 1
- 150000007530 organic bases Chemical group 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 125000005853 β-dimethylaminoethyl group Chemical group 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
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Verfahren zur Herstellung von neuen Derivaten von 5H.. Dibenzo [b, f] azepinen bzw. deren Salzen oder
Die vorliegende Erfindung betrifft ein Verfahren zur Herstellung von neuen Derivaten von 5H-Di- benzo [b, f) azepinen mit wertvollen pharmakologischen Eigenschaften.
5H-Dibenzo[b, f]azepin-lO (l1H) -one sowie Derivate derselben sind bisher nicht bekanntgeworden. Es wurde nun gefunden, dass N-Derivate solcher Verbindungen entsprechend der allgemeinen Formel
EMI1.1
worin X Wasserstoff, ein Halogenatom oder einen niedermolekularen Alkyl- oder Alkoxyrest, Y Wasserstoff, ein Halogenatom oder einen niedermolekularen Alkylrest, Z einen geradkettigen oder verzweigten Alkylenrest mit 2 - 6 Kohlenstoffatomen, und Am eine niedermolekulare Dialkylaminogruppe bedeutet, wobei einer der beiden Alkylreste von Am mit dem Alkylenrest Z (1), oder beide Alkylreste von Am unter sich direkt (2) oder über ein Sauerstoffatom (3), eine Alkylimino- (4), Hydroxyalkylimino- (5) oder Alkanoyloxyalkyllminogruppe (6) verbundensein können, wertvolle pharmakologische Eigenschaften,
insbesondere antiallergische, antiemetische, antikonvulsive und sedative Wirksamkeit, besitzen sowie, auch die Wirkung anderer Arzneistoffe, insbesondere von Narkotica, potenzieren.
Die folgenden Formeln sind spezielle Beispiele zur Erläuterung der oben erwähnten sechs Bindungsmöglichkeiten in der Gruppierung Z-Am
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EMI2.1
Quaternäre Ammoniumsalze, die sich von den vorstehend definierten tertiären Basen ableiten, wir- ) ken als Ganglioplegica. Die Herstellung der neuen Verbindungen kann durch Hydrolyse von 5-substituier- ten 10-Alkoxy-oder 10-Alkenyloxy-5H-dibenzo[b,f]azepinen der allgemeinen Formel
EMI2.2
worin R einen niedermolekularen Alkyl- oder Alkenylrest bedeutet und X, Y, Z und Am die oben angegebene Bedeutung haben, vorzugsweise in saurem Medium, z. B. in verdünnter Salzsäure, erfolgen.
Geeig- nete Ausgangsstöffe der allgemeinen Formel II sind beispielsweise
EMI2.3
[b, f] azepin,5- (γ-Dimethylamino-propyl)-10-methoxy-3,7-dichlor-5H-dibenzo[b,f]azepin, Smp.96
Die Ausgangsverbindungen der allgemeinen Formel II werden erhalten, wenn man gegebenenfalls substituierte 10-Alkoxy-oder 10-Alkenyloxy-5H-dibenzo[b,f]azepinen mit reaktionsfähigen Estern von Aminoalkoholen der allgemeinen Formel HO-Z- Am. 111 worin Z und Am die oben angegebene Bedeutung haben, umsetzt.
Die vorstehend erwähnten 10-Alkoxy-oder 10-Alkenyloxy-5H-dibenzo[b,f]azepinen können ausgehend von gegebenenfalls substituierten 5-Acyl-10,11-dihydro-5H-dibenzo[b,f]azepinen durch Bromierung in 10-Stellung mit Bromsuccinimid, Abspaltung von Bromwasserstoff, z. B. durch Erhitzen mit tertiären organischen Basen wie Collidin oder Behandlung mit alkoholischer Kalilauge in der Kälte, Anlagerung von Brom an die entstandenen 5-Acyl-5H-dibenzo[b,f]azepine, Behandlung der 10, 11-Dibromverbindungen
<Desc/Clms Page number 3>
EMI3.1
<Desc/Clms Page number 4>
5- (γ-Dimethylamino-propyl)-10-n.-butoxy-5H-dibenzo[b,f]azepin Kapo, ooze
EMI4.1
len 2-n.-Salzsäure 1 Stunde unter Rückfluss gekocht. Nach dem Abkühlen stellt man die Reaktionslösung mit konz.
Ammoniak alkalisch und löst das ausgeschiedene Öl in Äther. Die ätherische Lösung wird mit Wasser gewaschen, getrocknet und eingedampft. Bei der Destillation des Rückstandes im Hochvakuum erhält man das 5-(ss-Dimethylamino-äthyl)-5H-dibenzo[b,f]azepin-10(11H)-on vom Kp0,01 174 - 1750, Smp. 800.
Analog werden erhalten :
EMI4.2
EMI4.3
-Dimethylamino-propyl) -5H-dibenzo[b, f]azepin-10 (llH) -onKip., 01 2020.
<Desc / Clms Page number 1>
Process for the preparation of new derivatives of 5H .. dibenzo [b, f] azepines or their salts or
The present invention relates to a process for the preparation of new derivatives of 5H-dibenzo [b, f) azepines with valuable pharmacological properties.
5H-dibenzo [b, f] azepin-10 (11H) -one and derivatives thereof have not yet become known. It has now been found that N-derivatives of such compounds according to the general formula
EMI1.1
where X is hydrogen, a halogen atom or a low molecular weight alkyl or alkoxy group, Y is hydrogen, a halogen atom or a low molecular weight alkyl group, Z is a straight-chain or branched alkylene group having 2-6 carbon atoms, and Am is a low molecular weight dialkylamino group, one of the two alkyl groups of Am with the alkylene radical Z (1), or both alkyl radicals of Am can be linked directly (2) or via an oxygen atom (3), an alkylimino (4), hydroxyalkylimino (5) or alkanoyloxyalkyllmino group (6), valuable pharmacological properties ,
in particular have antiallergic, antiemetic, anticonvulsant and sedative effectiveness and also potentiate the effect of other drugs, especially narcotics.
The following formulas are specific examples to illustrate the above-mentioned six bond possibilities in the grouping Z-Am
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EMI2.1
Quaternary ammonium salts, which are derived from the tertiary bases defined above, act as ganglioplegics. The new compounds can be prepared by hydrolysis of 5-substituted 10-alkoxy- or 10-alkenyloxy-5H-dibenzo [b, f] azepines of the general formula
EMI2.2
where R is a low molecular weight alkyl or alkenyl radical and X, Y, Z and Am have the meanings given above, preferably in an acidic medium, e.g. B. in dilute hydrochloric acid.
Suitable starting materials of the general formula II are, for example
EMI2.3
[b, f] azepine, 5- (γ-dimethylamino-propyl) -10-methoxy-3,7-dichloro-5H-dibenzo [b, f] azepine, m.p.
The starting compounds of the general formula II are obtained if optionally substituted 10-alkoxy- or 10-alkenyloxy-5H-dibenzo [b, f] azepines with reactive esters of amino alcohols of the general formula HO-Z-Am. 111 in which Z and Am have the meanings given above.
The above-mentioned 10-alkoxy- or 10-alkenyloxy-5H-dibenzo [b, f] azepines can, starting from optionally substituted 5-acyl-10,11-dihydro-5H-dibenzo [b, f] azepines, by bromination in 10- Position with bromosuccinimide, elimination of hydrogen bromide, e.g. B. by heating with tertiary organic bases such as collidine or treatment with alcoholic potassium hydroxide solution in the cold, addition of bromine to the resulting 5-acyl-5H-dibenzo [b, f] azepine, treatment of the 10, 11-dibromo compounds
<Desc / Clms Page number 3>
EMI3.1
<Desc / Clms Page number 4>
5- (γ-dimethylamino-propyl) -10-n-butoxy-5H-dibenzo [b, f] azepine Kapo, ooze
EMI4.1
len 2-N hydrochloric acid refluxed for 1 hour. After cooling, the reaction solution is made with conc.
Ammonia is alkaline and dissolves the excreted oil in ether. The ethereal solution is washed with water, dried and evaporated. Distillation of the residue in a high vacuum gives 5- (ß-dimethylamino-ethyl) -5H-dibenzo [b, f] azepin-10 (11H) -one with a boiling point of 0.01 174-1750, melting point 800.
Analogously the following are obtained:
EMI4.2
EMI4.3
-Dimethylamino-propyl) -5H-dibenzo [b, f] azepin-10 (IIH) -onKip., 01 2020.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH222655X | 1959-11-16 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AT222655B true AT222655B (en) | 1962-08-10 |
Family
ID=4452712
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AT851060A AT222655B (en) | 1959-11-16 | 1960-11-15 | Process for the preparation of new derivatives of 5H-dibenzo [b, f] azepines or their salts or quaternary ammonium compounds |
Country Status (1)
| Country | Link |
|---|---|
| AT (1) | AT222655B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3185679A (en) * | 1965-05-25 | Azepine derivatives |
-
1960
- 1960-11-15 AT AT851060A patent/AT222655B/en active
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3185679A (en) * | 1965-05-25 | Azepine derivatives |
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