CH481055A - Process for the preparation of 5-aminomethylated 10,11-dihydro-5H-dibenzo (a, d) cycloheptene derivatives - Google Patents
Process for the preparation of 5-aminomethylated 10,11-dihydro-5H-dibenzo (a, d) cycloheptene derivativesInfo
- Publication number
- CH481055A CH481055A CH1716868A CH1716868A CH481055A CH 481055 A CH481055 A CH 481055A CH 1716868 A CH1716868 A CH 1716868A CH 1716868 A CH1716868 A CH 1716868A CH 481055 A CH481055 A CH 481055A
- Authority
- CH
- Switzerland
- Prior art keywords
- carbon atoms
- dibenzo
- aminomethylated
- dihydro
- preparation
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/33—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C211/34—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of rings other than six-membered aromatic rings of a saturated carbon skeleton
- C07C211/38—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of rings other than six-membered aromatic rings of a saturated carbon skeleton containing condensed ring systems
-
- 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
-
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Hydrogenated Pyridines (AREA)
Description
Verfahren zur Herstellung von 5-aminomethylierten 10,11-Dihydro-5H-dibenzo [a, d] cyclohepten-Derivaten
Gegenstand der Erfindung ist ein Verfahren zur Herstellung von neuen 5-aminomethylierten 10,11-Dihydro5H-dibenzo [a, d]-cycloheptenen der Formel :
EMI1.1
sowie von Säure-Additionssalzen davon. In Formel I bedeutet R, ein Wasserstoffatom oder eine höchstens 3 C Atome enthaltende Alkylgruppe. Die Reste Ra stellen höchstens 3 C-Atome enthaltende Alkylgruppen dar, und von den Resten Rg und R4 bedeutet der eine ein Wasserstoffatom und der andere ein Wasserstoffatom, ein Halogenatom oder eine höchstens 3 C-Atome enthaltende Alkylgruppe.
Die genannten Verbindungen zeigen, wie dies beim Elektroschock-Test [Methode von Goodman et al., J. Pharmacol. 108,168 (1953)] ersichtlich ist, starke antikonvulsive Wirksamkeit und kommen daher insbesondere als Antiepileptika in Betracht.
Verbindungen entsprechend Formel I werden erhalten, wenn man 5-aminomethylierte 5H-Dibenzo [a, d] cycloheptene der Formel :
EMI1.2
in welcher R, R,, und R4 die genannte Bedeutung haben, und von den Resten R'2 der eine höchstens 3 C Atome enthaltendes Alkyl, Alkenyl oder Alkinyl bedeutet und der andere höchstens 3 C-Atome enthaltendes Alkyl darstellt, hydriert.
Die Hydrierung erfolgt vorzugsweise in einem organischen Lösungsmittel, wie einem Alkohol oder Ester, durch Behandeln mit Wasserstoff in Gegenwart eines Katalysators, wie Palladium-Kohle, Raney-Nickel, Platin oder dergleichen.
Die nach diesem Verfahren erhaltenen Verbindungen entsprechend Formel I können sowohl als freie Basen als auch in Form ihrer Additionssalze mit geeigneten Säuren, wie Halogenwasserstoffsäuren, Toluolsul fonsäuren, Schwefelsäure, Salpetersäure, Phosphorsäure, Essigsäure, Oxalsäure, Malonsäure, Bernsteinsäure, Äpfelsäure, Maleinsäure oder Weinsäure, gewonnen und verwendet werden.
Beispiel 1
10 g 5-Dimethylaminomethyl-SH-dibenzo [a, d] cyclo- hepten (Hydrochlorid : Smp. 207-209 C) werden in 250 ml absolutem Athanol in Gegenwart von Raney Nickel bei 45 C unter Normaldruck mit Wasserstoff hydriert. Hierauf wird das Reaktionsgemisch zur Abtrennung des Katalysators filtriert und anschliessend eingedampft. Man erhält 9,7 g (97 O/o der Theorie) eines öligen Rückstandes bestehend aus 5-Dimethylaminomethyl-10,11-dihydro-5H-dibenzo [a, d] cyclohepten. Durch Behandeln dieses Rückstandes mit äthanolischer Salzsäure erhält man das entsprechende Hydrochlorid, welches nach Kristallisation aus Methanol/Äther den Schmelzpunkt 290-291 C zeigt.
Bei analogem Vorgehen wie in den vorerwähnten Beispielen erhält man aus den entsprechenden Ausgangsstoffen weiterhin z. B. die in der folgenden Tabelle angegebenen Produkte. In der Tabelle haben Ri, R2, R3 und R4 die früher genannte Bedeutung. spiOí Rt R2 Rs R4 Schmeízpunkt 2-CH3-CHs H H Hydrochlorid : 245-246 C 3 H-C2H H H Hydrochlorid : 250 C (Zers.) 4 H-CH3 2-Cl H Hydrochlorid : 301-305 C 5 H-CH3 2-CHs H Hydrochlorid : 234-235 C 6 H-CH3 H 7-Cl Hydrochlorid :
230-240 C 7 H-CH3 H 7-CH, Hydrochlorid : 230-231 C 8 H-CH3 1-Cl H Hydrochlorid : 254-256 C
Process for the preparation of 5-aminomethylated 10,11-dihydro-5H-dibenzo [a, d] cycloheptene derivatives
The invention relates to a process for the preparation of new 5-aminomethylated 10,11-dihydro5H-dibenzo [a, d] -cycloheptenes of the formula:
EMI1.1
as well as acid addition salts thereof. In formula I, R denotes a hydrogen atom or an alkyl group containing at most 3 carbon atoms. The radicals Ra represent alkyl groups containing at most 3 carbon atoms, and of the radicals Rg and R4, one denotes a hydrogen atom and the other denotes a hydrogen atom, a halogen atom or an alkyl group containing at most 3 carbon atoms.
The compounds mentioned show how this occurs in the electric shock test [method by Goodman et al., J. Pharmacol. 108, 168 (1953)], strong anticonvulsant effectiveness and are therefore particularly suitable as antiepileptic drugs.
Compounds corresponding to formula I are obtained if 5-aminomethylated 5H-dibenzo [a, d] cycloheptenes of the formula:
EMI1.2
in which R, R 1 and R 4 have the meaning mentioned, and of the radicals R '2, one is alkyl, alkenyl or alkynyl containing at most 3 carbon atoms and the other is alkyl containing at most 3 carbon atoms, hydrogenated.
The hydrogenation is preferably carried out in an organic solvent such as an alcohol or ester by treating with hydrogen in the presence of a catalyst such as palladium-carbon, Raney nickel, platinum or the like.
The compounds corresponding to formula I obtained by this process can be used both as free bases and in the form of their addition salts with suitable acids such as hydrohalic acids, toluene sulfonic acids, sulfuric acid, nitric acid, phosphoric acid, acetic acid, oxalic acid, malonic acid, succinic acid, malic acid, maleic acid or tartaric acid, obtained and used.
Example 1
10 g of 5-dimethylaminomethyl-SH-dibenzo [a, d] cycloheptene (hydrochloride: mp 207-209 ° C.) are hydrogenated with hydrogen in 250 ml of absolute ethanol in the presence of Raney nickel at 45 ° C. under atmospheric pressure. The reaction mixture is then filtered to separate off the catalyst and then evaporated. 9.7 g (97% of theory) of an oily residue consisting of 5-dimethylaminomethyl-10,11-dihydro-5H-dibenzo [a, d] cycloheptene are obtained. By treating this residue with ethanolic hydrochloric acid, the corresponding hydrochloride is obtained which, after crystallization from methanol / ether, has a melting point of 290-291 ° C.
In an analogous procedure to that in the aforementioned examples, the corresponding starting materials continue to give z. B. the products given in the following table. In the table, Ri, R2, R3 and R4 have the meaning given earlier. spiOí Rt R2 Rs R4 melting point 2-CH3-CHs HH hydrochloride: 245-246 C 3 H-C2H HH hydrochloride: 250 C (dec.) 4 H-CH3 2-Cl H hydrochloride: 301-305 C 5 H-CH3 2 -CHs H hydrochloride: 234-235 C 6 H-CH3 H 7-Cl hydrochloride:
230-240 C 7 H-CH3 H 7-CH, hydrochloride: 230-231 C 8 H-CH3 1-Cl H hydrochloride: 254-256 C
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1716868A CH481055A (en) | 1966-05-10 | 1966-05-10 | Process for the preparation of 5-aminomethylated 10,11-dihydro-5H-dibenzo (a, d) cycloheptene derivatives |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH678166A CH473759A (en) | 1966-05-10 | 1966-05-10 | Process for the preparation of 10,11-dihydro-5H-dibenzo (a, d) -cycloheptene derivatives |
| CH1716868A CH481055A (en) | 1966-05-10 | 1966-05-10 | Process for the preparation of 5-aminomethylated 10,11-dihydro-5H-dibenzo (a, d) cycloheptene derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH481055A true CH481055A (en) | 1969-11-15 |
Family
ID=4314928
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1716968A CH481869A (en) | 1966-05-10 | 1966-05-10 | Process for the preparation of 5-aminomethylated 10,11-dihydro-5H-dibenzo (a, d) cycloheptene derivatives |
| CH678166A CH473759A (en) | 1966-05-10 | 1966-05-10 | Process for the preparation of 10,11-dihydro-5H-dibenzo (a, d) -cycloheptene derivatives |
| CH1716868A CH481055A (en) | 1966-05-10 | 1966-05-10 | Process for the preparation of 5-aminomethylated 10,11-dihydro-5H-dibenzo (a, d) cycloheptene derivatives |
Family Applications Before (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1716968A CH481869A (en) | 1966-05-10 | 1966-05-10 | Process for the preparation of 5-aminomethylated 10,11-dihydro-5H-dibenzo (a, d) cycloheptene derivatives |
| CH678166A CH473759A (en) | 1966-05-10 | 1966-05-10 | Process for the preparation of 10,11-dihydro-5H-dibenzo (a, d) -cycloheptene derivatives |
Country Status (12)
| Country | Link |
|---|---|
| AT (3) | AT283311B (en) |
| BE (1) | BE698198A (en) |
| CH (3) | CH481869A (en) |
| CS (4) | CS154229B2 (en) |
| DE (1) | DE1643212A1 (en) |
| ES (1) | ES340257A1 (en) |
| FI (1) | FI47348C (en) |
| FR (1) | FR6502M (en) |
| GB (1) | GB1170798A (en) |
| GR (1) | GR36291B (en) |
| NL (1) | NL6706480A (en) |
| NO (1) | NO122246B (en) |
-
1966
- 1966-05-10 CH CH1716968A patent/CH481869A/en not_active IP Right Cessation
- 1966-05-10 CH CH678166A patent/CH473759A/en not_active IP Right Cessation
- 1966-05-10 CH CH1716868A patent/CH481055A/en not_active IP Right Cessation
-
1967
- 1967-05-03 FI FI671285A patent/FI47348C/en active
- 1967-05-03 DE DE19671643212 patent/DE1643212A1/en active Pending
- 1967-05-05 GB GB20979/67A patent/GB1170798A/en not_active Expired
- 1967-05-08 ES ES340257A patent/ES340257A1/en not_active Expired
- 1967-05-08 GR GR670136291A patent/GR36291B/en unknown
- 1967-05-09 AT AT870569A patent/AT283311B/en not_active IP Right Cessation
- 1967-05-09 BE BE698198D patent/BE698198A/xx unknown
- 1967-05-09 AT AT434967A patent/AT283303B/en not_active IP Right Cessation
- 1967-05-09 NO NO168071A patent/NO122246B/no unknown
- 1967-05-09 AT AT870769A patent/AT283312B/en not_active IP Right Cessation
- 1967-05-09 NL NL6706480A patent/NL6706480A/xx unknown
- 1967-05-10 FR FR105888A patent/FR6502M/fr not_active Expired
- 1967-05-10 CS CS281170*1A patent/CS154229B2/cs unknown
- 1967-05-10 CS CS337867A patent/CS154228B2/cs unknown
- 1967-05-10 CS CS281370*1A patent/CS154231B2/cs unknown
- 1967-05-10 CS CS281270*1A patent/CS154230B2/cs unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ES340257A1 (en) | 1968-09-01 |
| CS154228B2 (en) | 1974-03-29 |
| FR6502M (en) | 1968-12-02 |
| CS154230B2 (en) | 1974-03-29 |
| AT283312B (en) | 1970-08-10 |
| GR36291B (en) | 1969-01-20 |
| CS154231B2 (en) | 1974-03-29 |
| CS154229B2 (en) | 1974-03-29 |
| GB1170798A (en) | 1969-11-19 |
| CH481869A (en) | 1969-11-30 |
| CH473759A (en) | 1969-06-15 |
| FI47348B (en) | 1973-07-31 |
| FI47348C (en) | 1973-11-12 |
| AT283311B (en) | 1970-08-10 |
| BE698198A (en) | 1967-11-09 |
| NL6706480A (en) | 1967-11-13 |
| NO122246B (en) | 1971-06-07 |
| AT283303B (en) | 1970-08-10 |
| DE1643212A1 (en) | 1971-03-11 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased |