CH485653A - Process for the preparation of 10-aminoalkylated 5H-dibenzo (a, d) -cycloheptene derivatives - Google Patents
Process for the preparation of 10-aminoalkylated 5H-dibenzo (a, d) -cycloheptene derivativesInfo
- Publication number
- CH485653A CH485653A CH1909169A CH1909169A CH485653A CH 485653 A CH485653 A CH 485653A CH 1909169 A CH1909169 A CH 1909169A CH 1909169 A CH1909169 A CH 1909169A CH 485653 A CH485653 A CH 485653A
- Authority
- CH
- Switzerland
- Prior art keywords
- dibenzo
- aminoalkylated
- acid
- preparation
- cycloheptene
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 5
- QPJORFLSOJAUNL-UHFFFAOYSA-N dibenzo[a,d][7]annulene Chemical class C1=CC2=CC=CC=C2CC2=CC=CC=C21 QPJORFLSOJAUNL-UHFFFAOYSA-N 0.000 title claims description 4
- 238000002360 preparation method Methods 0.000 title claims description 4
- 239000002253 acid Substances 0.000 claims description 7
- 125000006239 protecting group Chemical group 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 239000002243 precursor Substances 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims 1
- 239000007795 chemical reaction product Substances 0.000 claims 1
- 239000012458 free base Substances 0.000 claims 1
- 150000007522 mineralic acids Chemical class 0.000 claims 1
- 150000007524 organic acids Chemical class 0.000 claims 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000001961 anticonvulsive agent Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- -1 psychosedativa Substances 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000003556 anti-epileptic effect Effects 0.000 description 1
- 229940125681 anticonvulsant agent Drugs 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 229940125688 antiparkinson agent Drugs 0.000 description 1
- 239000000939 antiparkinson agent Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 150000001933 cycloheptenes Chemical class 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000012433 hydrogen halide Substances 0.000 description 1
- 229910000039 hydrogen halide Inorganic materials 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229940035363 muscle relaxants Drugs 0.000 description 1
- 239000003158 myorelaxant agent Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/62—Preparation of compounds containing amino groups bound to a carbon skeleton by cleaving carbon-to-nitrogen, sulfur-to-nitrogen, or phosphorus-to-nitrogen bonds, e.g. hydrolysis of amides, N-dealkylation of amines or quaternary ammonium compounds
-
- 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
- C07C211/35—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 only non-condensed rings
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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)
Description
Verfahren zur Herstellung 10-aminoalkylierter 5H-Dibenzo [a, d]-cycloheptenderivate
Gegenstand der Erfindung ist ein Verfahren zur Herstellung neuer 1 0-aminoalkyliertcr 5H-Dibenw [a, d] cycloheptenderivate der Formel :
EMI1.1
worin R, die Methyl-oder Athylgruppe bedeutet, sowie von Säure-Additionssalzen davon.
Die genannten Verbindungen sind pharmakologisch aktive Stoffe, die günstige Wirkungen auf das Zentralnervensystem ausüben und insbesondere als Antikon- vulsiva, Antiepileptika, Tranquilizer, Psychosedativa, Muskelrelaxantien und Antiparkinson-Mitte in Betracht fallen.
Die gewünschten Verbindungen erhält man durch Hydrolysieren einer Vorstufe der Formel :
EMI1.2
in welcher Ri die genannte Bedeutung besitzt und R' eine hydrolytisch abspaltbare Schutzgruppe bedeutet.
Als hydrolytisch abspaltbare Schutzgruppe R'eignet sich z. B. ein insbesondere p-substituierter Benzsulfonylrest, wie Tosyl, pNitro-oder p-Brombenzsulfonyl, oder ein Acylrest.
Die nach diesem Verfahren erhaltenen 1 0-amino- alkylierten 5H-Dibenzo [a, d] cycloheptenderivate können sowohl als freie Basen als auch in Form ihrer Addi- tionssalze mit geeigneten Säuren, wie Halogenwasser stoffsäuren, Schwefelsäure, Salpetersäure, Phosphorsäure, Essigäure, Oxalsäure, Malonsäure, Bernstein- säure, Äpfelsäure, Maleinsäure, Weinsäure oder Toluolsulfonsäuren, gewonnen und verwendet werden.
Beispiel
1,5 g 5-Methylen-10- (N-methyl-N-tosyl-amino methyl)-SH-dibenzo [a, d] cyclohepten (Smp. 196195 C) werden bei 0 C zu 20g konzentrierter Schwefelsäure gegeben. Das Reaktionsgemisch wird hierauf 15 Stunden bei 0 C und anschliessend 3 Stunden bei Zimmer- temperatur gehalten und dann auf Eis gegossen. Nach dreimaligem Ausschütteln mit Chloroform wird dio saure wässerige Phase mit 30% iger Natronlauge alkalisch gestellt und viermal mit Äther ausgeschüttelt. Die Ätheraiuszüge werden mit Wasser gewaschen, mit Na triumsulfat getrocknet und eingedampft.
Der erhaltene ölige Rückstand wird mit ätherischer Malcinsäure in das Maleat übergeführt. Nach Kristallisation aus Aceton erhält man 0,95 g (70% der Theorie) 5-Methylen-10- methylamunomethyl5H-dibenzo [a, d] cyclohepten-Maleat in Form von farblosen Schuppen vom Schmelzpunkt 180 bis 185 C.
Process for the preparation of 10-aminoalkylated 5H-dibenzo [a, d] -cycloheptene derivatives
The invention relates to a process for the preparation of new 10-aminoalkylated 5H-Dibenw [a, d] cycloheptene derivatives of the formula:
EMI1.1
wherein R is the methyl or ethyl group, and acid addition salts thereof.
The compounds mentioned are pharmacologically active substances which exert beneficial effects on the central nervous system and are particularly suitable as anticonvulsants, antiepileptics, tranquilizers, psychosedativa, muscle relaxants and anti-Parkinson agents.
The desired compounds are obtained by hydrolyzing a precursor of the formula:
EMI1.2
in which Ri has the meaning mentioned and R 'denotes a hydrolytically cleavable protective group.
As a hydrolytically cleavable protective group R 'is suitable, for. B. a particularly p-substituted benzsulfonyl radical, such as tosyl, pnitro- or p-bromobenzsulfonyl, or an acyl radical.
The 10-aminoalkylated 5H-dibenzo [a, d] cycloheptene derivatives obtained by this process can be used both as free bases and in the form of their addition salts with suitable acids, such as hydrogen halide acids, sulfuric acid, nitric acid, phosphoric acid, acetic acid, oxalic acid Acid, malonic acid, succinic acid, malic acid, maleic acid, tartaric acid or toluenesulfonic acids, can be obtained and used.
example
1.5 g of 5-methylene-10- (N-methyl-N-tosylamino methyl) -SH-dibenzo [a, d] cycloheptene (melting point 196195 C) are added to 20 g of concentrated sulfuric acid at 0 C. The reaction mixture is then kept at 0 ° C. for 15 hours and then at room temperature for 3 hours and then poured onto ice. After shaking out three times with chloroform, the acidic aqueous phase is made alkaline with 30% sodium hydroxide solution and shaken out four times with ether. The ethereal extracts are washed with water, dried with sodium sulfate and evaporated.
The oily residue obtained is converted into the maleate with essential malcic acid. After crystallization from acetone, 0.95 g (70% of theory) of 5-methylene-10-methylamunomethyl5H-dibenzo [a, d] cycloheptene maleate are obtained in the form of colorless flakes with a melting point of 180 to 185 C.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1909169A CH485653A (en) | 1967-07-24 | 1967-07-24 | Process for the preparation of 10-aminoalkylated 5H-dibenzo (a, d) -cycloheptene derivatives |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1909169A CH485653A (en) | 1967-07-24 | 1967-07-24 | Process for the preparation of 10-aminoalkylated 5H-dibenzo (a, d) -cycloheptene derivatives |
| CH1050167A CH485650A (en) | 1967-07-24 | 1967-07-24 | Process for the preparation of 10-aminoalkylated 5H-dibenzo (a, d) -cycloheptene derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH485653A true CH485653A (en) | 1970-02-15 |
Family
ID=4363890
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1909169A CH485653A (en) | 1967-07-24 | 1967-07-24 | Process for the preparation of 10-aminoalkylated 5H-dibenzo (a, d) -cycloheptene derivatives |
| CH1050167A CH485650A (en) | 1967-07-24 | 1967-07-24 | Process for the preparation of 10-aminoalkylated 5H-dibenzo (a, d) -cycloheptene derivatives |
| CH1908969A CH485651A (en) | 1967-07-24 | 1967-07-24 | Process for the preparation of 10-aminoalkylated 5H-dibenzo (a, d) -cycloheptene derivatives |
| CH1909069A CH485652A (en) | 1967-07-24 | 1967-07-24 | Process for the preparation of 10-aminoalkylated 5H-dibenzo (a, d) -cycloheptene derivatives |
Family Applications After (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1050167A CH485650A (en) | 1967-07-24 | 1967-07-24 | Process for the preparation of 10-aminoalkylated 5H-dibenzo (a, d) -cycloheptene derivatives |
| CH1908969A CH485651A (en) | 1967-07-24 | 1967-07-24 | Process for the preparation of 10-aminoalkylated 5H-dibenzo (a, d) -cycloheptene derivatives |
| CH1909069A CH485652A (en) | 1967-07-24 | 1967-07-24 | Process for the preparation of 10-aminoalkylated 5H-dibenzo (a, d) -cycloheptene derivatives |
Country Status (7)
| Country | Link |
|---|---|
| BE (1) | BE718434A (en) |
| CH (4) | CH485653A (en) |
| DE (1) | DE1768706A1 (en) |
| FR (1) | FR7907M (en) |
| GB (1) | GB1185277A (en) |
| IL (1) | IL30368A0 (en) |
| NL (1) | NL6809838A (en) |
-
1967
- 1967-07-24 CH CH1909169A patent/CH485653A/en not_active IP Right Cessation
- 1967-07-24 CH CH1050167A patent/CH485650A/en not_active IP Right Cessation
- 1967-07-24 CH CH1908969A patent/CH485651A/en not_active IP Right Cessation
- 1967-07-24 CH CH1909069A patent/CH485652A/en not_active IP Right Cessation
-
1968
- 1968-06-21 DE DE19681768706 patent/DE1768706A1/en active Pending
- 1968-07-11 NL NL6809838A patent/NL6809838A/xx unknown
- 1968-07-15 GB GB33608/68A patent/GB1185277A/en not_active Expired
- 1968-07-15 IL IL30368A patent/IL30368A0/en unknown
- 1968-07-18 FR FR159699A patent/FR7907M/fr not_active Expired
- 1968-07-23 BE BE718434D patent/BE718434A/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IL30368A0 (en) | 1968-09-26 |
| GB1185277A (en) | 1970-03-25 |
| CH485651A (en) | 1970-02-15 |
| FR7907M (en) | 1970-05-11 |
| NL6809838A (en) | 1969-01-28 |
| CH485652A (en) | 1970-02-15 |
| BE718434A (en) | 1969-01-23 |
| CH485650A (en) | 1970-02-15 |
| DE1768706A1 (en) | 1971-11-18 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased |