CH299260A - Process for the preparation of a new disubstituted nicotinic acid amide. - Google Patents

Process for the preparation of a new disubstituted nicotinic acid amide.

Info

Publication number
CH299260A
CH299260A CH299260DA CH299260A CH 299260 A CH299260 A CH 299260A CH 299260D A CH299260D A CH 299260DA CH 299260 A CH299260 A CH 299260A
Authority
CH
Switzerland
Prior art keywords
nicotinic acid
acid amide
ethyl
preparation
new
Prior art date
Application number
Other languages
German (de)
Inventor
Aktiengesellschaft Cilag
Original Assignee
Cilag 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
Application filed by Cilag Ag filed Critical Cilag Ag
Publication of CH299260A publication Critical patent/CH299260A/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—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
    • 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
    • C07D213/60—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
    • C07D213/82—Amides; Imides in position 3

Description

  

      Verfahren    zur Herstellung eines neuen     disubstituierten        Nicotinsäureamids:       Gegenstand der Erfindung ist ein Verfah  ren zur Verstellung eines neuen     disubstituier-          ten        Nicotinsäureamids    der Formel  
EMI0001.0007     
    welches dadurch     gekennzeichnet    ist, dass man  eine das     Nicotinyl-Radikal    liefernde Verbin  dung mit einer den Rest  
EMI0001.0010     
    liefernden     Verbindung    umsetzt.  



  Als den     Nicotinsäurerest    liefernde     Verbin-          dung    seien beispielsweise erwähnt  Die     Nicotinsäure    selbst, ihre Ester, ihre       Halogenide,    ihr     Azid    und ihr     Anhydrid    bzw.  ihre gemischten     Anhydride,    z.

   B. mit Phos  phorsäure, Schwefelsäure     usf.    Als den     Amin-          rest    liefernde Verbindungen seien zum Bei  spiel das     N-(1,2-Diphenyl-äthyl)-N-(8-pyrro-          lidino-äthyl)-amin    selbst. sowie seine     N-Metall-          derivate    erwähnt. Die     Umsetzung    kann in An-    oder Abwesenheit eines     Lösungs-    bzw. Verdün  nungsmittels und eines     basisehen    Kondensa  tionsmittels erfolgen.     Als    Kondensationsmittel  kann auch das genannte Amin selbst dienen.  



  Das so erhaltene     Nicotinsäure-[N-(1,2-di-          phenyl    -     äthyl)    -N -     (ss-pyrrolidino-äthyl)    ]     -amid     bildet ein farbloses Öl, welches unter 0,08 mm  bei 245-250  siedet     und    sich gut in verdünn  ten Säuren, wenig in Wasser und     Petroläther     löst. Das Chlorhydrat     schmilzt    aus     Methyliso-          butylketon    umkristallisiert bei 188-190 .  



  Die Verbindung besitzt wertvolle     spasmo-          lytische    Eigenschaften und soll deshalb als  Arzneimittel, aber auch als Zwischenprodukt  zur Herstellung weiterer Derivate Verwen  dung finden.  



  <I>Beispiel 1:</I>  30,4 g     N-(1,2-Diphenyl-äthyl)-N-(,B-pyrro-          lidino-äthyl)-amin    und 37,8 g     Nicotinsäure-          anhydrid    werden, in je 200     cm3    warmem Ben  zol gelöst,. miteinander vermischt und mit 23 g  geglühter Pottasche 5     Stunden    gekocht. Nach  dem Erkalten wird einige Male mit verdünn  ter Natronlauge durchgeschüttelt, die Benzol  schicht dann mit Salzsäure ausgezogen, die       Salzsäurelösung    mit Kohle filtriert, mit Na  tronlauge alkalisch gemacht und das obenauf  schwimmende Öl in Chloroform aufgenommen.  Nach dem Verdampfen des Chloroforms wird  der Rückstand im Hochvakuum destilliert.

         Man        erhält        so        60,7%*        des        unter        0,08        mm        bei     245-250  siedenden     Nicotinsäure-[N-(1,2-di-          phenyl-äthyl)-N-(ss-pyrrolidino-äthyl)    ]     -amids.     Die neue Verbindung löst sich leicht in ver-           dünnten    Säuren,

   weniger gut in Wasser     und          Petroläther.    Das Chlorhydrat schmilzt aus       Methylisobutylketon        umkristallisiert    bei 188  bis 190 .  



       Beispiel   <I>2:</I>  Die gleiche Verbindung erhält man in  guter Reinheit und Ausbeute, wenn man     Nico-          tinsäure    und     N-(1,2-Diphenyl-äthyl)-N-(ss-          pyrrolidino-äthyl)-amin    bei erhöhter Tem  peratur zusammen erhitzt und das Reaktions  gemisch analog wie in Beispiel 1 beschrieben  aufarbeitet.



      Process for the production of a new disubstituted nicotinic acid amide: The subject matter of the invention is a process for the preparation of a new disubstituted nicotinic acid amide of the formula
EMI0001.0007
    which is characterized in that one of the nicotinyl radical supplying connection with a remainder
EMI0001.0010
    the supplying connection.



  Examples of the compound supplying the nicotinic acid residue are nicotinic acid itself, its esters, its halides, its azide and its anhydride or its mixed anhydrides, e.g.

   B. with phosphoric acid, sulfuric acid, etc. The amine residue supplying compounds are, for example, N- (1,2-diphenyl-ethyl) -N- (8-pyrrolidino-ethyl) -amine itself N-metal derivatives mentioned. The reaction can be carried out in the presence or absence of a solvent or diluent and a basic condensation agent. The amine mentioned itself can also serve as a condensing agent.



  The nicotinic acid [N- (1,2-diphenyl-ethyl) -N - (s-pyrrolidino-ethyl)] -amide obtained in this way forms a colorless oil which boils below 0.08 mm at 245-250 and becomes dissolves well in dilute acids, little in water and petroleum ether. The chlorohydrate melts from methyl isobutyl ketone recrystallized at 188-190.



  The compound has valuable spasmolytic properties and should therefore be used as a medicament, but also as an intermediate for the production of further derivatives.



  <I> Example 1: </I> 30.4 g of N- (1,2-diphenyl-ethyl) -N - (, B-pyrrolidino-ethyl) -amine and 37.8 g of nicotinic anhydride are, dissolved in 200 cm3 of warm benzene each. mixed together and cooked with 23 g of calcined potash for 5 hours. After cooling, it is shaken several times with dilute sodium hydroxide solution, the benzene layer is then extracted with hydrochloric acid, the hydrochloric acid solution is filtered with charcoal, made alkaline with sodium hydroxide solution and the oil floating on top is taken up in chloroform. After the chloroform has evaporated, the residue is distilled in a high vacuum.

         This gives 60.7% of the nicotinic acid [N- (1,2-diphenyl-ethyl) -N- (s-pyrrolidino-ethyl)] -amide boiling below 0.08 mm at 245-250. The new compound dissolves easily in dilute acids,

   less good in water and petroleum ether. The chlorohydrate melts from methyl isobutyl ketone recrystallized at 188-190.



       Example <I> 2: </I> The same compound is obtained in good purity and yield if nicotinic acid and N- (1,2-diphenyl-ethyl) -N- (s-pyrrolidino-ethyl) -amine are used Heated together at elevated temperature and the reaction mixture worked up analogously as described in Example 1.

Claims (1)

PATENTANSPRUCH: Verfahren zur Herstellung eines neuen di- substituierten Nicotinsäureamids der Formel EMI0002.0014 dadurch gekennzeichnet, dass man eine das Nicotinyl-Radikal liefernde Verbindung mit einer den Rest EMI0002.0016 liefernden Verbindung umsetzt. PATENT CLAIM: Process for the production of a new di-substituted nicotinic acid amide of the formula EMI0002.0014 characterized in that one provides the nicotinyl radical with a the remainder EMI0002.0016 the supplying connection. Das so erhaltene Nicotinsäure-[N-(1,2-di- phenyl-.äthyl) -N- (ss-pyrrolidino - äthyl) ] - amid bildet ein farbloses, unter 0,08 mm bei 245 bis 250 siedendes öl, das sich leicht in verdünn ten Säuren und wenig in Wasser und Petrol- äther löst. Das Chlorhydrat schmilzt aus Me- thylisobutylketon umkristallisiert bei 188 bis 190 . Die Verbindung soll als Spasmolytikum und als Zwischenprodukt Verwendung finden. . The nicotinic acid [N- (1,2-diphenyl-.äthyl) -N- (ss-pyrrolidino-ethyl)] amide obtained in this way forms a colorless oil which boils below 0.08 mm at 245-250 dissolves easily in dilute acids and slightly in water and petroleum ether. The chlorohydrate melts from methyl isobutyl ketone recrystallized at 188-190. The compound is said to be used as an antispasmodic and as an intermediate product. . UNTERANSPRUCH: Verfahren nach Patentanspruch, dadurch gekennzeichnet, dass man als das Nicotinyl- Radikal liefernde Verbindung Nicotinsäure- anhydrid verwendet. SUBCLAIM: Process according to patent claim, characterized in that nicotinic anhydride is used as the compound providing the nicotinyl radical.
CH299260D 1951-03-01 1951-03-01 Process for the preparation of a new disubstituted nicotinic acid amide. CH299260A (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
CH299269T 1951-03-01
CH296180T 1951-03-01
CH299260T 1951-03-01

Publications (1)

Publication Number Publication Date
CH299260A true CH299260A (en) 1954-05-31

Family

ID=27178223

Family Applications (1)

Application Number Title Priority Date Filing Date
CH299260D CH299260A (en) 1951-03-01 1951-03-01 Process for the preparation of a new disubstituted nicotinic acid amide.

Country Status (1)

Country Link
CH (1) CH299260A (en)

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