CH632251A5 - Process for preparing novel 2-naphthyl-substituted, cyclic, N-allylamine derivatives - Google Patents

Process for preparing novel 2-naphthyl-substituted, cyclic, N-allylamine derivatives Download PDF

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Publication number
CH632251A5
CH632251A5 CH1020377A CH1020377A CH632251A5 CH 632251 A5 CH632251 A5 CH 632251A5 CH 1020377 A CH1020377 A CH 1020377A CH 1020377 A CH1020377 A CH 1020377A CH 632251 A5 CH632251 A5 CH 632251A5
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Switzerland
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formula
integer
compound
hydrogen
naphthyl
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CH1020377A
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German (de)
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Helmut Dr Hamberger
Adrian Dr Stephen
Anton Dr Stuetz
Peter Dr Stuetz
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Sandoz Ag
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Priority to CH1020377A priority Critical patent/CH632251A5/en
Priority to EP78100611A priority patent/EP0000896B1/en
Priority to DE7878100611T priority patent/DE2862103D1/en
Priority to FI782446A priority patent/FI65774C/en
Priority to DK354678A priority patent/DK152114C/en
Priority to IL55382A priority patent/IL55382A/en
Priority to CA309,579A priority patent/CA1111852A/en
Priority to NZ188170A priority patent/NZ188170A/en
Priority to IE1670/78A priority patent/IE47314B1/en
Priority to ES472641A priority patent/ES472641A1/en
Priority to IT26835/78A priority patent/IT1098253B/en
Priority to AT602578A priority patent/AT366659B/en
Priority to US06/934,772 priority patent/US4680291A/en
Priority to PT68448A priority patent/PT68448A/en
Priority to AU39082/78A priority patent/AU526828B2/en
Priority to ZA784706A priority patent/ZA784706B/en
Priority to JP10137578A priority patent/JPS5441855A/en
Publication of CH632251A5 publication Critical patent/CH632251A5/en
Priority to MY40/85A priority patent/MY8500040A/en

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    • C07D203/08—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring nitrogen atom
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    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
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    • C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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    • C07D209/04—Indoles; Hydrogenated indoles
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    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
    • C07D211/14—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
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    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
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    • C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
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    • C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
    • C07D223/02—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings
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    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
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    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
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    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
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    • C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
    • C07D333/54—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
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Abstract

2-Naphthyl-substituted, cyclic, N-allylamine derivatives of the formula I, <IMAGE> in which R1, R2 and n have the meanings given in Patent Claim 1, and their acid addition salts, are prepared by reacting a compound of the formula III, <IMAGE> with a compound of the formula IV <IMAGE> (X = chlorine or bromine). The compounds of the formula I possess antimycotic activity.

Description

       

  
 

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

 



   PATENTANSPRÜCHE
1. Verfahren zur Herstellung neuer 2-Naphthylsubstituierter, zyklischer N-Allylaminderivate der Formel:
EMI1.1     
 worin R1 für Wasserstoff, eine niedere Alkyl- oder niedere Alkoxygruppe, n für eine ganze Zahl von 1 bis 8 und R2 für eine der Gruppen der Formeln:
EMI1.2     
 stehen, wobei R3 Wasserstoff, die Hydroxy-, eine niedere Alkoxyoder niedere Alkylgruppe, R4 eine Alkyl- oder Aralkylgruppe bedeuten, m für eine ganze Zahl von 0 bis 4, o für eine ganze Zahl von 0 bis 3 und p für eine ganze Zahl von 0 bis 5 stehen, und ihrer Säureadditionssalze, dadurch gekennzeichnet, dass man eine Verbindung der Formel:
EMI1.3     
 worin   Rl    und n obige Bedeutung besitzen, mit einer Verbindung der Formel:

  :    R2-CH=CH-CH2X    (IV) worin R2 obige Bedeutung besitzt und X für Chlor oder Brom steht, umsetzt und die erhaltenen Verbindungen der Formel I gegebenenfalls in ihre Säureadditionssalze überführt.



   2. Verfahren gemäss Patentanspruch 1, worin in der Verbindung der   Formeln    R, Wasserstoff und R2 Phenyl bedeuten und n für 4 steht.



   Die Erfindung betrifft ein Verfahren zur Herstellung neuer 2 Naphthylsubstituierter, zyklischer N-Allylaminderivate der Formel:
EMI1.4     
 worin   Rl    für Wasserstoff, eine niedere Alkyl- oder niedere Alkoxygruppe, n für eine ganze Zahl von 1 bis 8 und R2 für eine der Gruppen der Formeln:
EMI1.5     
 stehen, wobei R3 Wasserstoff, die Hydroxy-, eine niedere Alkoxyoder niedere Alkylgruppe, R4 eine Alkyl- oder Aralkylgruppe bedeuten, m für eine ganze Zahl von 0 bis 4, o für eine ganze Zahl von 0 bis 3 und p für eine ganze Zahl von 0 bis 5 stehen.



   Erfindungsgemäss gelangt man zu den Verbindungen der Formel I, indem man eine Verbindung der Formel:
EMI1.6     
 worin   Rl    und n obige Bedeutung besitzen, mit einer Verbindung der Formel:    R2-CH=CH-CH2X    (IV) worin R2 obige Bedeutung besitzt und X für Chlor oder Brom steht, umsetzt.



   Das erfindungsgemässe Verfahren kann beispielsweise ausgeführt werden, indem man eine Verbindung der Formel III in einem unter den Reaktionsbedingungen inerten Lösungsmittel z.B. in einem niederen Alkohol, in einem aromatischen Kohlenwasserstoff wie Benzol, in einem Äther wie Dioxan oder auch in Acetonitril, vorzugsweise in Dimethylformamid oder einem niederen Keton wie Aceton, löst oder suspendiert und eine Lösung bzw. Suspension einer Verbindung der Formel IV im gleichen Lösungsmittel zusetzt. Die Reaktionstemperatur kann zwischen   0 C    und Siedetemperatur des Reaktionsgemisches liegen, vorzugsweise wird die Reaktion bei Raumtemperatur oder leicht erhöhter Temperatur durchgeführt.

  Die bei dieser Umsetzung gebildete Säure kann nach bekannten Methoden aufgefangen werden, z.B. durch Zusatz eines Säureakzeptors wie eines Alkalimetallkarbonats oder eines tertiären Amins. Aus dem Reaktionsgemisch kann das Endprodukt nach an sich bekannten Methoden isoliert und gegebenenfalls gereinigt werden.  



   Die Verbindungen der Formel I können in ihre Säureadditions



  salze überführt werden und umgekehrt.



   Die durch R, und R3 definierten niederen Alkyl- und Alkoxygruppen besitzen vorzugsweise 1 bis 4 Kohlenstoffatome und bedeuten insbesondere die Methyl- oder Äthyl- bzw. die Methoxy- oder Äthoxygruppe. Die durch R4 dargestellte Alkylgruppe besitzt vorzugsweise 1 bis 12 Kohlenstoffatome, die Aralkylgruppe bedeutet vorzugsweise die Benzylgruppe. n steht vorzugsweise für 3 bis 5, insbesondere für 4.



   Die Verbindungen der Formel III sind entweder bekannt oder können analog zu bekannten Verfahren hergestellt werden, z.B. nach
EMI2.1     

In den Formeln V bis VII besitzen R, und n obige Bedeutung.



  Die Verbindungen der Formel IV und V sind bekannt oder können nach bekannten Verfahren bzw. analog zu bekannten Verfahren hergestellt werden.



   Die Verbindungen der Formel I besitzen chemotherapeutische Eigenschaften. Insbesondere besitzen die Verbindungen eine antimykotische Wirkung, wie sich durch Untersuchungen in vitro unter Verwendung von Myceten (z.B. von Trichophyton quinckeaneum) sowie in vivo sowohl bei dermaler als auch oraler Applikation am experimentellen Hautmykosemodell am Meerschweinchen zeigen lässt.



  Bei diesem Modell wird die Substanz in Polyäthylenglykol aufgenommen und 7 d hindurch einmal täglich auf der infizierten Hautoberfläche verrieben. Die antimykotische Wirkung konnte ab einer Konzentration von 0,1 bis 0,6% festgestellt werden. Die Verbindungen der Formel I können daher als Antimykotika verwendet werden.



  Die Verbindungen der Formel I können in Form der freien Basen oder in Form pharmazeutisch unbedenklicher Säureadditionssalze verwendet werden, wobei die Salze grössenordnungsmässig die gleiche Wirksamkeit besitzen wie die entsprechenden freien Basen. Geeignete Säureadditionssalze sind die Hydrochloride, Hydrogenfumarate und Naphthalin-1,5-disulfonate.



   Die Verbindungen der Formel I können mit üblichen pharmazeutisch unbedenklichen Verdünnungs- oder Trägermitteln vermischt und in Form von Salben oder Tinkturen verabreicht werden.



   In den nachfolgenden Beispielen, die die Erfindung näher erläutern, ihren Umfang aber in keiner Weise einschränken sollen, erfolgen alle Temperaturangaben in Celsiusgraden.



  Beispiel 1:    l-Cinnamyl-2-( I-naphthyl)piperidin   
16 g   2-(1-Naphthyl)piperidin    als Hydrochlorid und 27 g Na2CO3 anh. werden in 100 ml Dimethylformamid suspendiert und eine Lösung von 12,7 g Cinnamylbromid in Dimethylformamid zugetropft.



  Die Reaktionsmischung wird über Nacht bei Raumtemperatur gerührt, dann filtriert und das Lösungsmittel im Vakuum entfernt.



  Nach üblicher Aufarbeitung wird die Titelsubstanz durch Behandeln mit äthanolischer HCI als Hydrochlorid erhalten. Fp.: 203 bis   205 C.   



   Analog wie in Beispiel 1 beschrieben können auch folgende Verbindungen der Formel I erhalten werden (Beispiele 2 bis 7): Beispiel 2:    1-Cinnamyl-2- ( 1-naphthyl)pyrrolidin   
Fp.: 75 bis   78"C    (Base).



  Beispiel 3:    1- Cinnamyl-2- (1-naphthyl) -1-azacycloheptan   
Fp.: 171 bis   175"C (Hydrochlorid).   



  Beispiel 4:    2- (I -Naphthyl)piperidin-l -crotonsäure-n-amylester   
NMR   (CDCl3,    RT, TMS):   8    = 8,5(m,lH); 7,3 bis   8,0(m,6H); 6,7    bis 7,05(m,lH); 5,9(d,lH); 4,l(t,2H); 3,8 bis   4,0(m,lH);    3,1 bis 3,5(m,3H); 2,5 bis 2,8(dd,lH).



  Beispiel 5:    1-Cinnamyl-2-      (1-naphthyl)    aziridin
NMR   (CDCI3,    RTR, TMS):   8    = 7,0 bis 8,4(12H); 6,2 bis 6,8(m,2H); 3,4(d,lH); 2,95 bis 3,l(m,lH); 1,9 bis 2,l(m,2H).



  Beispiel 6:   
1-[3- (1- Cyclohexenyl) -cis- (2-propenyl) J-2- -napAthyl) piperidin   
NMR   (CDCl3,    RT, TMS):   8    = 8,3 bis   8,8(1H);    7,3 bis 8,0(6H); 5,8(d,lH, J = 13Hz); 5,2 bis 5,6(m,3H); 3,7 bis   4,0(1H);    3,1 bis 3,5(m,3H); 2,8 bis 3,l(dd,lH).



  Beispiel 7:    1-[3- (1-Cyclohexenyl) -trans- (2-propenyl) ]-2- (1-naphthyl) -    piperidin
NMR   (CDCl3,    RT, TMS): 8 = 8,3 bis   8,8(1H);    7,3 bis 8,0(6H); 5,9(d,lH, J = 16Hz); 5,2 bis 5,6(m,3H); 3,7 bis   4,0(1H);    3,0 bis   3,5(m,3H); 2,4    bis 2,7(dd,lH).



   Das als Ausgangsprodukt benötigte   2-(1-Naphthyl)piperidin    kann folgendermassen erhalten werden:
Aus 5,1 g Mg in 50 ml absolutem Äther wird durch Zutropfen einer Lösung von 43,4 g l-Bromnaphthalin in absolutem Äther der Grignard-Komplex hergestellt. Der Äther wird aus der Reaktionsmischung entfernt und durch absolutes Benzol ersetzt. Zu der siedenden Reaktionsmischung werden 8 g 6-Methoxy-2,3,4,5-tetrahydropyridin zugetropft. Nach weiteren 8 h wird gekühlt, mit gesättigter wässriger Ammonchloridlösung behandelt und das Reaktionsprodukt durch Schütteln mit wässriger   HC1-Lösung    aus der organischen Phase entfernt. Nach der Neutralisation der wässrigen Lösung und üblicher Aufarbeitung wird das erhaltene 2-(l-Naphthyl)3,4,5,6-tetrahydropyridin direkt in Methanol gelöst und mit einem Überschuss an NaBH4 reduziert. 

  Nach üblicher Aufarbeitung wird das Rohprodukt durch Behandeln mit alkoholischer   HC1-Lösung    in das Hydrochlorid überführt.



   Fp.: 280 bis   281"C.   



   Analog können auch die folgenden Verbindungen der Formel III erhalten werden:
2-( 1 -Naphthyl)pyrrolidin
Fp.: 212 bis   214"C    (Hydrochlorid)    2-(l-Naphthyl)-l -azacycloheptan       Fp.:218    bis   221"C    (Hydrochlorid). 



  
 

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

 



   PATENT CLAIMS
1. Process for the preparation of new 2-naphthyl-substituted, cyclic N-allylamine derivatives of the formula:
EMI1.1
 wherein R1 is hydrogen, a lower alkyl or lower alkoxy group, n is an integer from 1 to 8 and R2 is one of the groups of the formulas:
EMI1.2
 stand, wherein R3 is hydrogen, the hydroxyl, a lower alkoxy or lower alkyl group, R4 is an alkyl or aralkyl group, m is an integer from 0 to 4, o is an integer from 0 to 3 and p is an integer from 0 to 5, and their acid addition salts, characterized in that a compound of the formula:
EMI1.3
 wherein Rl and n have the above meaning, with a compound of the formula:

  : R2-CH = CH-CH2X (IV) in which R2 has the above meaning and X is chlorine or bromine, and the compounds of formula I obtained are converted into their acid addition salts, if necessary.



   2. The method according to claim 1, wherein in the compound of the formulas R, hydrogen and R2 are phenyl and n is 4.



   The invention relates to a process for the preparation of new 2 naphthyl-substituted, cyclic N-allylamine derivatives of the formula:
EMI1.4
 wherein R1 is hydrogen, a lower alkyl or lower alkoxy group, n is an integer from 1 to 8 and R2 is one of the groups of the formulas:
EMI1.5
 stand, wherein R3 is hydrogen, the hydroxyl, a lower alkoxy or lower alkyl group, R4 is an alkyl or aralkyl group, m is an integer from 0 to 4, o is an integer from 0 to 3 and p is an integer from 0 to 5 are available.



   According to the invention, the compounds of the formula I are obtained by using a compound of the formula:
EMI1.6
 wherein Rl and n have the above meaning, with a compound of the formula: R2-CH = CH-CH2X (IV) in which R2 has the above meaning and X represents chlorine or bromine.



   The process according to the invention can be carried out, for example, by reacting a compound of the formula III in a solvent which is inert under the dissolved or suspended in a lower alcohol, in an aromatic hydrocarbon such as benzene, in an ether such as dioxane or also in acetonitrile, preferably in dimethylformamide or a lower ketone such as acetone, and a solution or suspension of a compound of the formula IV in the same solvent is added . The reaction temperature can be between 0 ° C. and the boiling point of the reaction mixture; the reaction is preferably carried out at room temperature or at a slightly elevated temperature.

  The acid formed in this reaction can be collected by known methods, e.g. by adding an acid acceptor such as an alkali metal carbonate or a tertiary amine. The end product can be isolated from the reaction mixture by known methods and optionally purified.



   The compounds of formula I can in their acid additions



  salts are transferred and vice versa.



   The lower alkyl and alkoxy groups defined by R 1 and R 3 preferably have 1 to 4 carbon atoms and in particular mean the methyl or ethyl or the methoxy or ethoxy group. The alkyl group represented by R4 preferably has 1 to 12 carbon atoms, the aralkyl group preferably means the benzyl group. n is preferably 3 to 5, in particular 4.



   The compounds of formula III are either known or can be prepared analogously to known processes, e.g. to
EMI2.1

In the formulas V to VII, R and n have the above meaning.



  The compounds of the formula IV and V are known or can be prepared by known processes or analogously to known processes.



   The compounds of formula I have chemotherapeutic properties. In particular, the compounds have an antifungal effect, as can be demonstrated by in vitro investigations using mycetes (e.g. Trichophyton quinckeaneum) and in vivo both in dermal and oral application to the experimental skin mycosis model on guinea pigs.



  In this model, the substance is taken up in polyethylene glycol and rubbed on the infected skin surface once a day for 7 days. The antifungal effect could be determined from a concentration of 0.1 to 0.6%. The compounds of formula I can therefore be used as antifungals.



  The compounds of the formula I can be used in the form of the free bases or in the form of pharmaceutically acceptable acid addition salts, the salts being of the same order of magnitude as the corresponding free bases. Suitable acid addition salts are the hydrochlorides, hydrogen fumarates and naphthalene-1,5-disulfonates.



   The compounds of the formula I can be mixed with customary pharmaceutically acceptable diluents or carriers and administered in the form of ointments or tinctures.



   In the following examples, which explain the invention in more detail but are not intended to restrict its scope in any way, all the temperatures are given in degrees Celsius.



  Example 1: 1-Cinnamyl-2- (I-naphthyl) piperidine
16 g of 2- (1-naphthyl) piperidine as hydrochloride and 27 g of Na2CO3 app. are suspended in 100 ml of dimethylformamide and a solution of 12.7 g of cinnamyl bromide in dimethylformamide is added dropwise.



  The reaction mixture is stirred at room temperature overnight, then filtered and the solvent removed in vacuo.



  After the usual work-up, the title substance is obtained as the hydrochloride by treatment with ethanolic HCl. Fp .: 203 to 205 C.



   The following compounds of the formula I can also be obtained analogously to that described in Example 1 (Examples 2 to 7): Example 2: 1-cinnamyl-2- (1-naphthyl) pyrrolidine
Mp .: 75 to 78 "C (base).



  Example 3: 1-Cinnamyl-2- (1-naphthyl) -1-azacycloheptane
Mp .: 171 to 175 "C (hydrochloride).



  Example 4: 2- (I -naphthyl) piperidine-l -crotonic acid-n-amyl ester
NMR (CDCl3, RT, TMS): 8 = 8.5 (m, 1H); 7.3 to 8.0 (m, 6H); 6.7 to 7.05 (m, 1H); 5.9 (d, 1H); 4.1 (t, 2H); 3.8 to 4.0 (m, 1H); 3.1 to 3.5 (m, 3H); 2.5 to 2.8 (dd, lH).



  Example 5: 1-Cinnamyl-2- (1-naphthyl) aziridine
NMR (CDCI3, RTR, TMS): 8 = 7.0 to 8.4 (12H); 6.2 to 6.8 (m, 2H); 3.4 (d, 1H); 2.95 to 3.1 (m, lH); 1.9 to 2.1 (m, 2H).



  Example 6:
1- [3- (1-Cyclohexenyl) cis- (2-propenyl) J-2- napAthyl) piperidine
NMR (CDCl3, RT, TMS): 8 = 8.3 to 8.8 (1H); 7.3 to 8.0 (6H); 5.8 (d, 1H, J = 13 Hz); 5.2 to 5.6 (m, 3H); 3.7 to 4.0 (1H); 3.1 to 3.5 (m, 3H); 2.8 to 3.1 (dd, lH).



  Example 7: 1- [3- (1-Cyclohexenyl) trans (2-propenyl)] -2- (1-naphthyl) piperidine
NMR (CDCl3, RT, TMS): 8 = 8.3 to 8.8 (1H); 7.3 to 8.0 (6H); 5.9 (d, 1H, J = 16 Hz); 5.2 to 5.6 (m, 3H); 3.7 to 4.0 (1H); 3.0 to 3.5 (m, 3H); 2.4 to 2.7 (dd, lH).



   The 2- (1-naphthyl) piperidine required as the starting product can be obtained as follows:
The Grignard complex is prepared from 5.1 g of Mg in 50 ml of absolute ether by dropwise addition of a solution of 43.4 g of l-bromonaphthalene in absolute ether. The ether is removed from the reaction mixture and replaced with absolute benzene. 8 g of 6-methoxy-2,3,4,5-tetrahydropyridine are added dropwise to the boiling reaction mixture. After a further 8 h, the mixture is cooled, treated with saturated aqueous ammonium chloride solution and the reaction product is removed from the organic phase by shaking with aqueous HC1 solution. After neutralization of the aqueous solution and customary workup, the 2- (l-naphthyl) 3,4,5,6-tetrahydropyridine obtained is dissolved directly in methanol and reduced with an excess of NaBH4.

  After the usual work-up, the crude product is converted into the hydrochloride by treatment with an alcoholic HC1 solution.



   Mp .: 280 to 281 "C.



   The following compounds of the formula III can also be obtained analogously:
2- (1-naphthyl) pyrrolidine
Mp: 212 to 214 "C (hydrochloride) 2- (l-naphthyl) -l -azacycloheptane mp: 218 to 221" C (hydrochloride).

Claims (2)

PATENTANSPRÜCHE 1. Verfahren zur Herstellung neuer 2-Naphthylsubstituierter, zyklischer N-Allylaminderivate der Formel: EMI1.1 worin R1 für Wasserstoff, eine niedere Alkyl- oder niedere Alkoxygruppe, n für eine ganze Zahl von 1 bis 8 und R2 für eine der Gruppen der Formeln: EMI1.2 stehen, wobei R3 Wasserstoff, die Hydroxy-, eine niedere Alkoxyoder niedere Alkylgruppe, R4 eine Alkyl- oder Aralkylgruppe bedeuten, m für eine ganze Zahl von 0 bis 4, o für eine ganze Zahl von 0 bis 3 und p für eine ganze Zahl von 0 bis 5 stehen, und ihrer Säureadditionssalze, dadurch gekennzeichnet, dass man eine Verbindung der Formel: EMI1.3 worin Rl und n obige Bedeutung besitzen, mit einer Verbindung der Formel:  PATENT CLAIMS 1. Process for the preparation of new 2-naphthyl-substituted, cyclic N-allylamine derivatives of the formula: EMI1.1  wherein R1 is hydrogen, a lower alkyl or lower alkoxy group, n is an integer from 1 to 8 and R2 is one of the groups of the formulas: EMI1.2  stand, where R3 is hydrogen, the hydroxy, a lower alkoxy or lower alkyl group, R4 is an alkyl or aralkyl group, m is an integer from 0 to 4, o is an integer from 0 to 3 and p is an integer from 0 to 5, and their acid addition salts, characterized in that a compound of the formula: EMI1.3  wherein Rl and n have the above meaning, with a compound of the formula: : R2-CH=CH-CH2X (IV) worin R2 obige Bedeutung besitzt und X für Chlor oder Brom steht, umsetzt und die erhaltenen Verbindungen der Formel I gegebenenfalls in ihre Säureadditionssalze überführt. : R2-CH = CH-CH2X (IV) in which R2 has the meaning given above and X represents chlorine or bromine, and the compounds of formula I obtained are converted into their acid addition salts if necessary. 2. Verfahren gemäss Patentanspruch 1, worin in der Verbindung der Formeln R, Wasserstoff und R2 Phenyl bedeuten und n für 4 steht.  2. The method according to claim 1, wherein in the compound of the formulas R, hydrogen and R2 are phenyl and n is 4. Die Erfindung betrifft ein Verfahren zur Herstellung neuer 2 Naphthylsubstituierter, zyklischer N-Allylaminderivate der Formel: EMI1.4 worin Rl für Wasserstoff, eine niedere Alkyl- oder niedere Alkoxygruppe, n für eine ganze Zahl von 1 bis 8 und R2 für eine der Gruppen der Formeln: EMI1.5 stehen, wobei R3 Wasserstoff, die Hydroxy-, eine niedere Alkoxyoder niedere Alkylgruppe, R4 eine Alkyl- oder Aralkylgruppe bedeuten, m für eine ganze Zahl von 0 bis 4, o für eine ganze Zahl von 0 bis 3 und p für eine ganze Zahl von 0 bis 5 stehen.  The invention relates to a process for the preparation of new 2 naphthyl-substituted, cyclic N-allylamine derivatives of the formula: EMI1.4  wherein R1 is hydrogen, a lower alkyl or lower alkoxy group, n is an integer from 1 to 8 and R2 is one of the groups of the formulas: EMI1.5  stand, wherein R3 is hydrogen, the hydroxyl, a lower alkoxy or lower alkyl group, R4 is an alkyl or aralkyl group, m is an integer from 0 to 4, o is an integer from 0 to 3 and p is an integer from 0 to 5 are available. Erfindungsgemäss gelangt man zu den Verbindungen der Formel I, indem man eine Verbindung der Formel: EMI1.6 worin Rl und n obige Bedeutung besitzen, mit einer Verbindung der Formel: R2-CH=CH-CH2X (IV) worin R2 obige Bedeutung besitzt und X für Chlor oder Brom steht, umsetzt.  According to the invention, the compounds of the formula I are obtained by using a compound of the formula: EMI1.6  wherein Rl and n have the above meaning, with a compound of the formula: R2-CH = CH-CH2X (IV) in which R2 has the above meaning and X represents chlorine or bromine. Das erfindungsgemässe Verfahren kann beispielsweise ausgeführt werden, indem man eine Verbindung der Formel III in einem unter den Reaktionsbedingungen inerten Lösungsmittel z.B. in einem niederen Alkohol, in einem aromatischen Kohlenwasserstoff wie Benzol, in einem Äther wie Dioxan oder auch in Acetonitril, vorzugsweise in Dimethylformamid oder einem niederen Keton wie Aceton, löst oder suspendiert und eine Lösung bzw. Suspension einer Verbindung der Formel IV im gleichen Lösungsmittel zusetzt. Die Reaktionstemperatur kann zwischen 0 C und Siedetemperatur des Reaktionsgemisches liegen, vorzugsweise wird die Reaktion bei Raumtemperatur oder leicht erhöhter Temperatur durchgeführt.  The process according to the invention can be carried out, for example, by using a compound of the formula III in a solvent which is inert under the reaction conditions, e.g. dissolved or suspended in a lower alcohol, in an aromatic hydrocarbon such as benzene, in an ether such as dioxane or also in acetonitrile, preferably in dimethylformamide or a lower ketone such as acetone, and a solution or suspension of a compound of the formula IV in the same solvent is added . The reaction temperature can be between 0 ° C. and the boiling point of the reaction mixture; the reaction is preferably carried out at room temperature or at a slightly elevated temperature. Die bei dieser Umsetzung gebildete Säure kann nach bekannten Methoden aufgefangen werden, z.B. durch Zusatz eines Säureakzeptors wie eines Alkalimetallkarbonats oder eines tertiären Amins. Aus dem Reaktionsgemisch kann das Endprodukt nach an sich bekannten Methoden isoliert und gegebenenfalls gereinigt werden. **WARNUNG** Ende CLMS Feld konnte Anfang DESC uberlappen**. The acid formed in this reaction can be collected by known methods, e.g. by adding an acid acceptor such as an alkali metal carbonate or a tertiary amine. The end product can be isolated from the reaction mixture by known methods and optionally purified. ** WARNING ** End of CLMS field could overlap beginning of DESC **.
CH1020377A 1977-08-19 1977-08-19 Process for preparing novel 2-naphthyl-substituted, cyclic, N-allylamine derivatives CH632251A5 (en)

Priority Applications (18)

Application Number Priority Date Filing Date Title
CH1020377A CH632251A5 (en) 1977-08-19 1977-08-19 Process for preparing novel 2-naphthyl-substituted, cyclic, N-allylamine derivatives
EP78100611A EP0000896B1 (en) 1977-08-19 1978-08-07 Propenyl amines, processes for their production and pharmaceutical compositions containing them
DE7878100611T DE2862103D1 (en) 1977-08-19 1978-08-07 Propenyl amines, processes for their production and pharmaceutical compositions containing them
FI782446A FI65774C (en) 1977-08-19 1978-08-10 REFERENCE FOR A LOADER THERAPEUTIC FRAME
DK354678A DK152114C (en) 1977-08-19 1978-08-10 METHOD OF ANALOGUE FOR THE PREPARATION OF PROPENYLAMINES OR PHARMACEUTICAL ACCEPTABLE SALTS THEREOF
ES472641A ES472641A1 (en) 1977-08-19 1978-08-17 Propenyl amines, processes for their production and pharmaceutical compositions containing them.
CA309,579A CA1111852A (en) 1977-08-19 1978-08-17 Propenyl-amines, processes for their production and pharmaceutical compositions containing them
NZ188170A NZ188170A (en) 1977-08-19 1978-08-17 Propenylamines and pharmaceutical compositions
IE1670/78A IE47314B1 (en) 1977-08-19 1978-08-17 Propenyl amines,processes for their production and pharmaceutical compositions containing them
IL55382A IL55382A (en) 1977-08-19 1978-08-17 Propenylamines,their production and pharmaceutical compositions containing them
US06/934,772 US4680291A (en) 1977-08-19 1978-08-18 Propenylamines, processes for their production and pharmaceutical compositions containing them
AT602578A AT366659B (en) 1977-08-19 1978-08-18 METHOD FOR PRODUCING NEW ALLYLAMINE
IT26835/78A IT1098253B (en) 1977-08-19 1978-08-18 PROPENYL-AMMINES, PROCEDURES FOR THEIR PRODUCTION, AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
PT68448A PT68448A (en) 1977-08-19 1978-08-18 PROCESS FOR THE PREPARATION OF A PHARMACEUTICAL COMPOSITION CONTAINING NOVEL ORGANIC COMPOUNDS
AU39082/78A AU526828B2 (en) 1977-08-19 1978-08-18 Propenyl-amines
ZA784706A ZA784706B (en) 1977-08-19 1978-08-18 Propenylamines,processes for their production and pharmaceutical compositions containing them
JP10137578A JPS5441855A (en) 1977-08-19 1978-08-19 Propenylamine*its manufacture and medical composition containing it
MY40/85A MY8500040A (en) 1977-08-19 1985-12-30 Propenylamines, processes for their production and pharmaceutical compositions containing them

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CH1020377A CH632251A5 (en) 1977-08-19 1977-08-19 Process for preparing novel 2-naphthyl-substituted, cyclic, N-allylamine derivatives

Publications (1)

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CH632251A5 true CH632251A5 (en) 1982-09-30

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