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CH297291A - 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
CH297291A
CH297291A CH297291DA CH297291A CH 297291 A CH297291 A CH 297291A CH 297291D A CH297291D A CH 297291DA CH 297291 A CH297291 A CH 297291A
Authority
CH
Switzerland
Prior art keywords
nicotinic acid
preparation
ethyl
acid amide
new disubstituted
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 CH297291A publication Critical patent/CH297291A/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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pyridine Compounds (AREA)

Description

  

  Verfahren     zur    Herstellung     eines    neuen     disubstituierten        Nieotinsäureamids.       Gegenstand der Erfindung ist ein     Verfali-          i-c-n    zur     Herstellung    eines neuen     disubstituier-          teii        @\icotinsiiureamids.    der Formel  
EMI0001.0011     
          -elches        dadurch    gekennzeichnet ist,

       dass    man       einen    reaktionsfähigen Ester des Alkohols der  Formel  
EMI0001.0016     
         init        einer    den Rest.  
EMI0001.0019     
    liefernden Verbindung umsetzt.  



  Als reaktionsfähige Ester des Alkohols I  kann man beispielsweise einen Halogenwasser  stoffsäure-, einen Schwefelsäure-, einen     Alkyl-          bzw.        Arylsulfonsäureester    verwenden.     Statt     des freien     Aminoalkoholesters    kann auch ein       Salz    eines solchen zur Reaktion gebracht     wer-          den.       Vorteilhaft.

   verwendet man als den Rest     II     liefernde Verbindung ein     N-Metallderivat    des       7I    entsprechenden     Amids.    Man kann aber auch  das freie     Amid        II    unter Zuhilfenahme eines       Metallamids    als Kondensationsmittel mit einem  reaktionsfähigen     Aminoalkoholester    zur Reak  tion bringen.  



  Das so erhaltene     Nicotinsäure-N-        (1,2-di-          phenyl    -     ätliy    1) -N - (2'-     niorpholino        -äthyl)        -ainid     bildet ein zähes (>1, welches unter 0,08 mm  bei 280 bis     290     siedet und sich gut in ver  dünnten Säuren, wenig in Wasser und     Pe-          troläther    löst. Das     Chloroplatinat    schmilzt bei  <B>185</B> bis 188  unter Zersetzung. Die neue Ver  bindung soll als     Spasmolytikum    und als Zwi  schenprodukt zur Herstellung weiterer De  rivate Verwendung finden.

           Beispiel:     15,1     g        Nicotinsättre-N-(1,2-diphenyl-äthyl)-          amid,    suspendiert in 150     cm3        absol.    Benzol,  werden mit 2,3 g gepulvertem     Natriumamid     versetzt und kurze Zeit auf Siedetemperatur  erhitzt, wobei eine starke     Ammoniakentwick-          lung    eintritt.

   Nachdem die     Casentwieklung     nachgelassen hat, lässt man 8,3g     Morpholino-          äthylchlorid,    gelöst in 150     em33        absol.    Benzol,       zutropfen    und rührt dann weitere 7 Stunden  unter     Rückflusskoehen.    Nach dem     Erkalten.     wird die Lösung vom     überschüssigen        Natrium-          amid        abdekantiert        und    mit 60  warmer 1,5n  Salzsäure ausgezogen, bis der Auszug schwach  sauer reagiert..

       Der    noch warme salzsaure Aus  zog wird mit. Kohle filtriert, mit Lauge alkali-           siert,    erschöpfend     ausgeäthert    und der Äther       abdestilliert.    Der     Rüekstand    wird im     Hoch-          vakuum    destilliert, wobei man das unter  0,08 mm bei 280 bis 290" siedende     Nicotin-          säure-N-(1,2    -     dipheny    1-     äthyl)-N-    (2'-     inorpho-          lino-äthyl)

  -amid    als zähes Öl in einer Ausbeute  von 60     %        gewinnt.     



  Das     Chloroplatinat    der Verbindung     sehmilzt     bei 185 bis 188  unter Zersetzung.  



  An Stelle von     Natriumamid    als Konden  sationsmittel kann man das     Nicotinsäure-N-          (1,2-diphenyl-äthyl)        -amid    mit Natrium behan  deln und das entstandene     Natriumsalz    an  schliessend mit     llorpholino-äthylchlorid    kon  densieren, wobei die gleiche Verbindung in  befriedigender Ausbeute und Reinheit gewon  nen wird.



  Process for the preparation of a new disubstituted nieotinamide. The invention relates to a process for the production of a new disubstituted teii @ \ icotinsiiureamids. the formula
EMI0001.0011
          -which is characterized by

       that one is a reactive ester of the alcohol of the formula
EMI0001.0016
         init one the rest.
EMI0001.0019
    the supplying connection.



  The reactive ester of alcohol I can be, for example, a hydrogen halide, a sulfuric acid, an alkyl or aryl sulfonic acid ester. Instead of the free amino alcohol ester, a salt of such can also be reacted. Advantageous.

   an N-metal derivative of the amide corresponding to 7I is used as the compound supplying radical II. But you can also bring the free amide II with the aid of a metal amide as a condensation agent with a reactive amino alcohol ester to reac tion.



  The nicotinic acid-N- (1,2-diphenyl-ethyl 1) -N- (2'-niorpholino-ethyl) -ainide obtained in this way forms a tough (> 1, which boils below 0.08 mm at 280 to 290 and dissolves well in dilute acids, little in water and petroleum ether. The chloroplatinate melts with decomposition at <B> 185 </B> to 188. The new compound is intended as an antispasmodic and as an intermediate in the manufacture of other derivatives Find use.

           Example: 15.1 g of nicotine saturation N- (1,2-diphenyl-ethyl) amide, suspended in 150 cm3 of absolute. Benzene, 2.3 g of powdered sodium amide are added and the mixture is heated to boiling temperature for a short time, during which time a strong evolution of ammonia occurs.

   After the development of casings has subsided, 8.3 g of morpholino ethyl chloride, dissolved in 150 em33 absolute, are left. Benzene, add dropwise and then stir under reflux for a further 7 hours. After cooling down. the solution is decanted off from the excess sodium amide and extracted with 60 warm 1.5N hydrochloric acid until the extract reacts slightly acidic.

       The still warm hydrochloric acid is pulled out with. Coal is filtered, alkalized with lye, exhausted with ether and the ether is distilled off. The residue is distilled in a high vacuum, the nicotinic acid-N- (1,2-dipheny 1- ethyl) -N- (2'-inorpholino- (2'-inorpholino-) boiling below 0.08 mm at 280 to 290 " ethyl)

  -amid wins as a viscous oil in a yield of 60%.



  The chloroplatinate of the compound melts at 185 to 188 with decomposition.



  Instead of sodium amide as a condensation agent, the nicotinic acid-N- (1,2-diphenyl-ethyl) -amide can be treated with sodium and the resulting sodium salt condenses with lloropholino-ethyl chloride, the same compound in satisfactory yield and Purity is gained.

Claims (1)

PATENTANSPRUCH: Verfahren zur Herstellung eines neuen di- substituierten Nieotinsä.ureamids der Formel EMI0002.0026 dadurch gekennzeichnet, clah man einen reak tionsfähigen Ester des Alkohols der Formel EMI0002.0029 mit einer den Rest EMI0002.0030 liefernden Verbindung umsetzt. Das so erhaltene Nieotinsäure-N - (1,2-di- pheny 1- äthyl) - N - (2'- morpholino -äthy 1) PATENT CLAIM: Process for the preparation of a new disubstituted Nieotinsä.ureamids of the formula EMI0002.0026 characterized in that a reactive ester of the alcohol of the formula is clah EMI0002.0029 with one the rest EMI0002.0030 the supplying connection. The resulting nieotinic acid-N - (1,2-dipheny 1-ethyl) - N - (2'-morpholino-ethy 1) -amid bildet ein zähes Öl, welches unter 0,08 mm bei 280 bis 290 siedet und sieh leieht in ver dünnten Säuren, wenig in Wasser und Pe- troläther löst. Die Verbindung soll als Spasmolytikuni und als Zwischenprodukt Verwendung finden. UNTERANSPRUCH: Verfahren nach Patentanspruch, dadureli gekennzeichnet, dass man 1@Iorpholino-ätliyl- chlorid in Gegenwart von N atriumamid mit Nicotinsäure-N-(1,2-diphenyl-äthyl)-ainid um setzt. -amid forms a viscous oil, which boils below 0.08 mm at 280 to 290 and does not dissolve in dilute acids, but dissolves little in water and petroleum ether. The compound is said to be used as an antispasmodic and as an intermediate product. SUBSTANTIAL CLAIM: Process according to patent claim, characterized by the fact that 1 @ Iorpholino-ätliyl- chloride in the presence of N atriumamid with nicotinic acid-N- (1,2-diphenyl-ethyl) -ainide to.
CH297291D 1951-03-01 1951-03-01 Process for the preparation of a new disubstituted nicotinic acid amide. CH297291A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CH294511T 1951-03-01
CH297291T 1951-03-01

Publications (1)

Publication Number Publication Date
CH297291A true CH297291A (en) 1954-03-15

Family

ID=25733481

Family Applications (1)

Application Number Title Priority Date Filing Date
CH297291D CH297291A (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) CH297291A (en)

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