CH536839A - Indolyloxypropanolamine deriv - with beta-blocking activity - Google Patents

Indolyloxypropanolamine deriv - with beta-blocking activity

Info

Publication number
CH536839A
CH536839A CH88871A CH88871A CH536839A CH 536839 A CH536839 A CH 536839A CH 88871 A CH88871 A CH 88871A CH 88871 A CH88871 A CH 88871A CH 536839 A CH536839 A CH 536839A
Authority
CH
Switzerland
Prior art keywords
formula
addition salts
acid addition
phenyl
methyl
Prior art date
Application number
CH88871A
Other languages
German (de)
Inventor
Seemann Fritz
Troxler Franz
Original Assignee
Sandoz Ag
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Priority claimed from CH437770A external-priority patent/CH529753A/en
Application filed by Sandoz Ag filed Critical Sandoz Ag
Priority to CH88871A priority Critical patent/CH536839A/en
Publication of CH536839A publication Critical patent/CH536839A/en

Links

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
    • C07D209/30—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

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Indole Compounds (AREA)

Abstract

4- 2-hydroxy-3-(2-methyl-4-phenyl-2-butylamino) propoxy indole-2-carboxamide (I) and its acid addition salts.

Description

  

  
 



   Die Erfindung betrifft ein Verfahren zur Herstellung   ies    neuen   4-[2-Hydroxy-3-(2-methyl.4-phenyl-2-butyl-      mino)propoxyindol.2.carboxamids    der Formel I und seiner Säureadditionssalze.



   Erfindungsgemäss werden die Verbindungen der For   mel    I und ihre Säureadditionssalze wie im Hauptpatent Nr. 529 753 beschrieben hergestellt.



   Das Verfahren ist dadurch gekennzeichnet, dass man Verbindungen der Formel II, worin R niederes Alkyl bedeutet, mit der Verbindung der Formel III umsetzt u.



     rewünschtenfalls    die so erhaltenen Verbindungen der Formel I in ihre Säureadditionssalze überführt.



   Die Umsetzung kann nach einem für die Herstellung analoger Verbindungen bekannten Verfahren durchgerührt werden und erfolgt beispielsweise in einem Lösungs   mittel    wie Methanol, bei erhöhter Temperatur und mit Vorteil im Autoklaven.



   Die Ausgangsprodukte werden wie im Hauptpatent Nr. 529 753 beschrieben hergestellt.



   Die Verbindung der Formel I und ihre Säureaddi   ionssalze    besitzen eine Blockerwirkung auf die adrener   aschen      -Rezeptoren    und können daher u.a. zur Prophylaxe und Therapie von Koronarerkrankungen, insbesondere zur Behandlung von Angina pectoris, eingesetzt werden.



   Im nachfolgenden Beispiel, das die Erfindung näher erläutert, ihren Umfang aber in keiner Weise einschränken soll, erfolgen alle Temperaturangaben in Celsiusgralen und sind unkorrigiert.



   Beispiel   
4-[2-Hydroxy-3X2-methyl-4-phenyl-2-hutylamino)- propoxyjindol-2-carboxamid   
26,1   g 4-(2,3 -Epoxypropoxy)indol-2-carbonsäureäthyl-    ster, 20 g 2-Methyl-4-phenyl-2-butylamin und 200 ml Dioxan werden während 12 Stunden zum Sieden erhitzt.



  Man verdampft unter vermindertem Druck zur Trockne, nimmt den Rückstand in Essigester auf und extrahiert nit Weinsäure die basischen Bestandteile. Die vereinig :en weinsauren Phasen werden unter Kühlung mit Soda ösung alkalisch gestellt, mit Methylenchlorid extrahiert   md    die Methylenchloridextrakte, nach dem Trocknen iber Magnesiumsulfat, unter vermindertem Druck einbedampft. Der verbleibende rohe, ölige   4-[2-Hydroxy-3-       (2-methyl - 4- phenyl-2.butylamino)propoxy]indol-2-car-    bonsäureäthylester wird direkt in 750 ml gesättigter methanolischer Ammoniaklösung aufgenommen und im Autoklaven 5 Tage auf 1500 erhitzt. Man verdampft unter vermindertem Druck zur Trockne und chromatographiert den Rückstand an wassergesättigtem Kieselgel mit Methylenchlorid   +    5% Methanol. 

  Die so gereinigte Titelverbindung wird schliesslich in ihr Hydrogenmaleinat überführt, Smp. 219-2200.
EMI1.1     




   PATENTANSPRUCH



   Verfahren zur Herstellung von 4-[2-Hydroxy-3-(2-methyl-4-phenyl-2-   butylamino)propoxygindol-2-carboxamid    der Formel I und seiner Säureadditionssalze, dadurch gekennzeichnet, dass man Verbindungen der Formel II, worin R niederes Alkyl bedeutet, mit der Verbindung der Formel III umsetzt und gewünschtenfalls die so erhaltene Verbindung der Formel I in ihre Säureadditionssalze überführt.

**WARNUNG** Ende DESC Feld konnte Anfang CLMS uberlappen**.



   



  
 



   The invention relates to a process for the production of this new 4- [2-hydroxy-3- (2-methyl.4-phenyl-2-butylmino) propoxyindole.2.carboxamids of the formula I and its acid addition salts.



   According to the invention, the compounds of the formula I and their acid addition salts are prepared as described in main patent no. 529,753.



   The process is characterized in that compounds of the formula II, in which R is lower alkyl, are reacted with the compound of the formula III and the like.



     if desired, the compounds of the formula I thus obtained are converted into their acid addition salts.



   The reaction can be carried out by a method known for the preparation of analogous compounds and is carried out, for example, in a solvent such as methanol, at elevated temperature and advantageously in an autoclave.



   The starting products are produced as described in main patent no. 529 753.



   The compound of the formula I and its acid addition salts have a blocking effect on the adrenal ash receptors and can therefore i.a. for the prophylaxis and therapy of coronary diseases, in particular for the treatment of angina pectoris.



   In the following example, which explains the invention in more detail but is not intended to restrict its scope in any way, all temperature data are given in degrees Celsius and are uncorrected.



   example
4- [2-Hydroxy-3X2-methyl-4-phenyl-2-hutylamino] -propoxyindole-2-carboxamide
26.1 g of ethyl 4- (2,3-epoxypropoxy) indole-2-carboxylic acid, 20 g of 2-methyl-4-phenyl-2-butylamine and 200 ml of dioxane are heated to the boil for 12 hours.



  It is evaporated to dryness under reduced pressure, the residue is taken up in ethyl acetate and the basic constituents are extracted with tartaric acid. The combined tartaric phases are made alkaline while cooling with soda solution, extracted with methylene chloride and the methylene chloride extracts, after drying over magnesium sulfate, evaporated under reduced pressure. The remaining crude, oily ethyl 4- [2-hydroxy-3- (2-methyl-4-phenyl-2.butylamino) propoxy] indole-2-carboxylate is taken up directly in 750 ml of saturated methanolic ammonia solution and placed in an autoclave for 5 days heated to 1500. It is evaporated to dryness under reduced pressure and the residue is chromatographed on water-saturated silica gel with methylene chloride + 5% methanol.

  The title compound, purified in this way, is finally converted into its hydrogen maleate, mp 219-2200.
EMI1.1




   PATENT CLAIM



   Process for the preparation of 4- [2-hydroxy-3- (2-methyl-4-phenyl-2-butylamino) propoxygindole-2-carboxamide of the formula I and its acid addition salts, characterized in that compounds of the formula II in which R is lower alkyl, is reacted with the compound of the formula III and, if desired, the compound of the formula I thus obtained is converted into its acid addition salts.

** WARNING ** End of DESC field could overlap beginning of CLMS **.

Claims (1)

**WARNUNG** Anfang CLMS Feld konnte Ende DESC uberlappen **. ** WARNING ** Beginning of CLMS field could overlap end of DESC **. Die Erfindung betrifft ein Verfahren zur Herstellung ies neuen 4-[2-Hydroxy-3-(2-methyl.4-phenyl-2-butyl- mino)propoxyindol.2.carboxamids der Formel I und seiner Säureadditionssalze. The invention relates to a process for the production of this new 4- [2-hydroxy-3- (2-methyl.4-phenyl-2-butylmino) propoxyindole.2.carboxamids of the formula I and its acid addition salts. Erfindungsgemäss werden die Verbindungen der For mel I und ihre Säureadditionssalze wie im Hauptpatent Nr. 529 753 beschrieben hergestellt. According to the invention, the compounds of the formula I and their acid addition salts are prepared as described in main patent no. 529,753. Das Verfahren ist dadurch gekennzeichnet, dass man Verbindungen der Formel II, worin R niederes Alkyl bedeutet, mit der Verbindung der Formel III umsetzt u. The process is characterized in that compounds of the formula II, in which R is lower alkyl, are reacted with the compound of the formula III and the like. rewünschtenfalls die so erhaltenen Verbindungen der Formel I in ihre Säureadditionssalze überführt. if desired, the compounds of the formula I thus obtained are converted into their acid addition salts. Die Umsetzung kann nach einem für die Herstellung analoger Verbindungen bekannten Verfahren durchgerührt werden und erfolgt beispielsweise in einem Lösungs mittel wie Methanol, bei erhöhter Temperatur und mit Vorteil im Autoklaven. The reaction can be carried out by a method known for the preparation of analogous compounds and is carried out, for example, in a solvent such as methanol, at elevated temperature and advantageously in an autoclave. Die Ausgangsprodukte werden wie im Hauptpatent Nr. 529 753 beschrieben hergestellt. The starting products are produced as described in main patent no. 529 753. Die Verbindung der Formel I und ihre Säureaddi ionssalze besitzen eine Blockerwirkung auf die adrener aschen -Rezeptoren und können daher u.a. zur Prophylaxe und Therapie von Koronarerkrankungen, insbesondere zur Behandlung von Angina pectoris, eingesetzt werden. The compound of the formula I and its acid addition salts have a blocking effect on the adrenal ash receptors and can therefore i.a. for the prophylaxis and therapy of coronary diseases, in particular for the treatment of angina pectoris. Im nachfolgenden Beispiel, das die Erfindung näher erläutert, ihren Umfang aber in keiner Weise einschränken soll, erfolgen alle Temperaturangaben in Celsiusgralen und sind unkorrigiert. In the following example, which explains the invention in more detail but is not intended to restrict its scope in any way, all temperature data are given in degrees Celsius and are uncorrected. Beispiel 4-[2-Hydroxy-3X2-methyl-4-phenyl-2-hutylamino)- propoxyjindol-2-carboxamid 26,1 g 4-(2,3 -Epoxypropoxy)indol-2-carbonsäureäthyl- ster, 20 g 2-Methyl-4-phenyl-2-butylamin und 200 ml Dioxan werden während 12 Stunden zum Sieden erhitzt. example 4- [2-Hydroxy-3X2-methyl-4-phenyl-2-hutylamino] -propoxyindole-2-carboxamide 26.1 g of ethyl 4- (2,3-epoxypropoxy) indole-2-carboxylic acid, 20 g of 2-methyl-4-phenyl-2-butylamine and 200 ml of dioxane are heated to the boil for 12 hours. Man verdampft unter vermindertem Druck zur Trockne, nimmt den Rückstand in Essigester auf und extrahiert nit Weinsäure die basischen Bestandteile. Die vereinig :en weinsauren Phasen werden unter Kühlung mit Soda ösung alkalisch gestellt, mit Methylenchlorid extrahiert md die Methylenchloridextrakte, nach dem Trocknen iber Magnesiumsulfat, unter vermindertem Druck einbedampft. Der verbleibende rohe, ölige 4-[2-Hydroxy-3- (2-methyl - 4- phenyl-2.butylamino)propoxy]indol-2-car- bonsäureäthylester wird direkt in 750 ml gesättigter methanolischer Ammoniaklösung aufgenommen und im Autoklaven 5 Tage auf 1500 erhitzt. Man verdampft unter vermindertem Druck zur Trockne und chromatographiert den Rückstand an wassergesättigtem Kieselgel mit Methylenchlorid + 5% Methanol. It is evaporated to dryness under reduced pressure, the residue is taken up in ethyl acetate and the basic constituents are extracted with tartaric acid. The combined tartaric phases are made alkaline while cooling with soda solution, extracted with methylene chloride and the methylene chloride extracts, after drying over magnesium sulfate, evaporated under reduced pressure. The remaining crude, oily ethyl 4- [2-hydroxy-3- (2-methyl-4-phenyl-2.butylamino) propoxy] indole-2-carboxylate is taken up directly in 750 ml of saturated methanolic ammonia solution and placed in an autoclave for 5 days heated to 1500. It is evaporated to dryness under reduced pressure and the residue is chromatographed on water-saturated silica gel with methylene chloride + 5% methanol. Die so gereinigte Titelverbindung wird schliesslich in ihr Hydrogenmaleinat überführt, Smp. 219-2200. EMI1.1 The title compound, purified in this way, is finally converted into its hydrogen maleate, mp 219-2200. EMI1.1 PATENTANSPRUCH PATENT CLAIM Verfahren zur Herstellung von 4-[2-Hydroxy-3-(2-methyl-4-phenyl-2- butylamino)propoxygindol-2-carboxamid der Formel I und seiner Säureadditionssalze, dadurch gekennzeichnet, dass man Verbindungen der Formel II, worin R niederes Alkyl bedeutet, mit der Verbindung der Formel III umsetzt und gewünschtenfalls die so erhaltene Verbindung der Formel I in ihre Säureadditionssalze überführt. Process for the preparation of 4- [2-hydroxy-3- (2-methyl-4-phenyl-2-butylamino) propoxygindole-2-carboxamide of the formula I and its acid addition salts, characterized in that compounds of the formula II in which R is lower alkyl, is reacted with the compound of the formula III and, if desired, the compound of the formula I thus obtained is converted into its acid addition salts.
CH88871A 1970-03-24 1971-01-21 Indolyloxypropanolamine deriv - with beta-blocking activity CH536839A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CH88871A CH536839A (en) 1970-03-24 1971-01-21 Indolyloxypropanolamine deriv - with beta-blocking activity

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CH437770A CH529753A (en) 1970-03-24 1970-03-24 4-indolyl-amino ethers
CH88871A CH536839A (en) 1970-03-24 1971-01-21 Indolyloxypropanolamine deriv - with beta-blocking activity

Publications (1)

Publication Number Publication Date
CH536839A true CH536839A (en) 1973-05-15

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CH (1) CH536839A (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0014951A2 (en) * 1979-02-16 1980-09-03 Roche Diagnostics GmbH Heterocyclic oxypropanolamine derivatives, process for their preparation and medicines containing these compounds

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0014951A2 (en) * 1979-02-16 1980-09-03 Roche Diagnostics GmbH Heterocyclic oxypropanolamine derivatives, process for their preparation and medicines containing these compounds
EP0014951A3 (en) * 1979-02-16 1981-02-04 Boehringer Mannheim Gmbh Heterocyclic oxypropanolamine derivatives, process for their preparation and medicines containing these compounds

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