DE1134674B - Process for the production of indole derivatives and their salts - Google Patents
Process for the production of indole derivatives and their saltsInfo
- Publication number
- DE1134674B DE1134674B DES56160A DES0056160A DE1134674B DE 1134674 B DE1134674 B DE 1134674B DE S56160 A DES56160 A DE S56160A DE S0056160 A DES0056160 A DE S0056160A DE 1134674 B DE1134674 B DE 1134674B
- Authority
- DE
- Germany
- Prior art keywords
- indole derivatives
- salts
- radical
- general formula
- hydrogen atom
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 229940054051 antipsychotic indole derivative Drugs 0.000 title claims description 9
- 150000002475 indoles Chemical class 0.000 title claims description 9
- 238000000034 method Methods 0.000 title claims description 7
- 150000003839 salts Chemical class 0.000 title claims description 6
- -1 alkyl radical Chemical class 0.000 claims description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 239000003054 catalyst Substances 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical compound [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 claims description 2
- 230000004048 modification Effects 0.000 claims description 2
- 238000012986 modification Methods 0.000 claims description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 125000001041 indolyl group Chemical group 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- NHGVZTMBVDFPHJ-UHFFFAOYSA-N formyl fluoride Chemical compound FC=O NHGVZTMBVDFPHJ-UHFFFAOYSA-N 0.000 description 1
- 230000022244 formylation Effects 0.000 description 1
- 238000006170 formylation reaction Methods 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N hydrochloric acid Substances Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
Description
Verfahren zur Herstellung von Indolderivaten und deren Salzen Gegenstand der Patentanmeldung S 51571 1Vd/12p ist ein Verfahren zur Herstellung von Indolderivaten der allgemeinen Formel in der R und R, Wasserstoffatome, niedermolekulare Alkylreste oder Aralkylreste, X ein Wasserstoff- oder Halogenatom, einen niedermolekularen Alkyl- oder Alkoxyrest oder eine Oxygruppe und B einen 1-Alkylpiperidyl-, 1-Aralkylpiperidyl- oder 1-Alkyl-1,2,5,6-tetrahydropyridylrest, der in der 2- oder 4-Stellung des Piperidin- oder Tetrahydropyridinrings an dem Indolring gebunden und gegebenenfalls durch einen niedermolekularen Alkylrest substituiert ist, bedeuten, und deren Salzen, bei dem man Indolderivate der allgemeinen Formel in der B' einen Rest der in 2- oder 4-Stellung am Indolring gebunden ist und in dem Hal ein Halogenatom, R' einen niedermolekularen Alkylrest oder einen Aralkylrest und R" ein Wasserstoffatom oder einen niedermolekularen Alkylrest bedeuten, in Gegenwart von Platindioxyd als Katalysator in alkoholischem oder wäßrig-alkoholischem Medium bei gewöhnlichem Druck und gewöhnlicher Temperatur in an sich bekannter Weise hydriert oder mit Alkaliborhydriden reduziert und gegebenenfalls die erhaltenen Basen mit Säuren behandelt. Es wurde nun gefunden, daß man Indolderivate der allgemeinen Formel in der R ein Wasserstoffatom, einen niedermolekularen Alkylrest oder einen Aralkylrest und R' einen Methylrest bedeuten, und deren Salze in Abänderung des Verfahrens zur Herstellung dieser Indolderivate und deren Salze gemäß Patentanmeldung S 51571 IVb/12p erhält, wenn man die entsprechenden Indolderivate, in deren allgemeiner Formel R' ein Wasserstoffatom darstellt, in an sich bekannter Weise mit einem Formylierungsmittel behandelt und die erhaltenen formylierten Derivate gleichzeitig oder anschließend mit Wasserstoff in Gegenwart eines Katalysators hydriert oder mit Lithiumaluminiumhydrid reduziert.Process for the preparation of indole derivatives and their salts The subject of patent application S 51571 1Vd / 12p is a process for the preparation of indole derivatives of the general formula in which R and R, hydrogen atoms, low molecular weight alkyl radicals or aralkyl radicals, X a hydrogen or halogen atom, a low molecular weight alkyl or alkoxy radical or an oxy group and B a 1-alkylpiperidyl-, 1-aralkylpiperidyl- or 1-alkyl-1,2, 5,6-tetrahydropyridyl radical, which is bonded to the indole ring in the 2- or 4-position of the piperidine or tetrahydropyridine ring and is optionally substituted by a low molecular weight alkyl radical, and their salts, in which indole derivatives of the general formula in the B 'a remainder which is bonded to the indole ring in the 2- or 4-position and in which Hal is a halogen atom, R 'is a low molecular weight alkyl radical or an aralkyl radical and R "is a hydrogen atom or a low molecular weight alkyl radical, in the presence of platinum dioxide as a catalyst in alcoholic or aqueous-alcoholic The medium is hydrogenated at normal pressure and temperature in a manner known per se or reduced with alkali borohydrides and, if appropriate, the bases obtained are treated with acids. It has now been found that indole derivatives of the general formula can be used in which R is a hydrogen atom, a low molecular weight alkyl radical or an aralkyl radical and R 'is a methyl radical, and the salts thereof in a modification of the process for the preparation of these indole derivatives and their salts according to patent application S 51571 IVb / 12p are obtained when the corresponding indole derivatives are obtained in their general formula R 'represents a hydrogen atom, treated in a manner known per se with a formylating agent and the formylated derivatives obtained are hydrogenated simultaneously or subsequently with hydrogen in the presence of a catalyst or reduced with lithium aluminum hydride.
Die Formylierung wird nach an sich bekannten Methoden durchgeführt, insbesondere durch Einwirkung von Formamid, Animoniumformiat, Formylfluorid oder Ameisensäure.The formylation is carried out according to methods known per se, especially through action of formamide, ammonium formate, formyl fluoride or formic acid.
Das folgende Beispiel erläutert das erfindungsgemäße Verfahren.The following example explains the method according to the invention.
Beispiel Man erhitzt eine Lösung von 30 g 2-Piperidyl-(2')-3-äthylindol in 120 cem Forinamid zum Rückfluß. Während 30 Minuten. erfolgt eine Freisetzung von Ammoniak. Die erhaltene rote Lösung wird abgekühlt und in 800 ccm Wasser gegossen. Das formyllerte Derivat wird mit 350 ccm Chloroform extrahiert. Der Extrakt wird mit 200 cem 2n-Essigsäure und 600 cem Wasser gewaschen. Nach dem Trocknen und Verdampfen des Chloroforms erhält man 29g 2-[1'-Formylpiperidyl-(2')]-3-äthylindol. F. 174-C.EXAMPLE A solution of 30 g of 2-piperidyl- (2 ') -3-ethylindole in 120 cem forinamide is heated to reflux. For 30 minutes. ammonia is released. The red solution obtained is cooled and poured into 800 ccm of water. The formylated derivative is extracted with 350 ccm of chloroform. The extract is washed with 200 cem 2N acetic acid and 600 cem water. After drying and evaporation of the chloroform, 29 g of 2- [1'-formylpiperidyl- (2 ')] -3-ethylindole are obtained. F. 174-C.
Ein Gemisch aus 40 ccm wasserfreiem Tetrahydrofuran und 0,75 g Lithiumaluminiumhydrid versetzt man in 10 Minuten mit einer aus 20 ccm wasserfreiem Tetrahydrofuran und 5 g 2-[1'-Formylpiperidyl-(2')]-3-äthylindol gebildeten Lösung. Die Temperatur steigt, und man erhitzt 2 Stunden zum Rückfluß. Nach der Zerstörung des Komplexes und des überschüssigen Hydrids mit 10 ccm Wasser wird das Aluminiumoxyd abgesaugt und das Filtrat mit 25 ccm n-Salzsäure angesäuert. Man versetzt mit 30 ccm Wasser und verdampft das Tetrahydrofuran im Vakuum.A mixture of 40 cc of anhydrous tetrahydrofuran and 0.75 g of lithium aluminum hydride is mixed in 10 minutes with a solution formed from 20 cc of anhydrous tetrahydrofuran and 5 g of 2- [1'-formylpiperidyl- (2 ')] - 3-ethylindole. The temperature rises and the mixture is refluxed for 2 hours. After the complex and the excess hydride have been destroyed with 10 cc of water, the aluminum oxide is suctioned off and the filtrate is acidified with 25 cc of n-hydrochloric acid. 30 cc of water are added and the tetrahydrofuran is evaporated off in vacuo.
Die erhaltene wäßrige Lösung wird über Aktivkohle filtriert, mit 5 cem Natronlauge (d = 1,33) alkalisch gemacht und mit 90 ccm Äther extrahiert. Nach dem Trocknen und Verdampfen des Äthers erhält man 4 g 2-[1'-Methyl-piperidyl-(2')]-3-äthylindol, dessen Fumarat einen Schmelzpunkt von 190 bis 192'C aufweist.The aqueous solution obtained is filtered through activated charcoal, made alkaline with 5 cc sodium hydroxide solution (d = 1.33) and extracted with 90 cc ether. After drying and evaporation of the ether, 4 g of 2- [1'-methyl-piperidyl- (2 ')] -3-ethylindole, the fumarate of which has a melting point of 190 to 192 ° C., are obtained.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR1134674X | 1957-01-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1134674B true DE1134674B (en) | 1962-08-16 |
Family
ID=9639449
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DES56160A Pending DE1134674B (en) | 1957-01-09 | 1957-12-06 | Process for the production of indole derivatives and their salts |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE1134674B (en) |
-
1957
- 1957-12-06 DE DES56160A patent/DE1134674B/en active Pending
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