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CH297289A - 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
CH297289A
CH297289A CH297289DA CH297289A CH 297289 A CH297289 A CH 297289A CH 297289D A CH297289D A CH 297289DA CH 297289 A CH297289 A CH 297289A
Authority
CH
Switzerland
Prior art keywords
amide
nicotinic acid
ethyl
preparation
acid amide
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 CH297289A publication Critical patent/CH297289A/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        Nicotinsäureamids.            Gegenstand    der Erfindung ist ein Verfah  ren zur Herstellung eines neuen     disubstituier-          ten        Nicotinsäureamids    der Formel  
EMI0001.0011     
    welches dadurch     gekennzeichnet    ist, dass man  einen reaktionsfähigen Ester des Alkohols der  Formel  
EMI0001.0013     
    mit. einer den Rest  
EMI0001.0014     
    liefernden Verbindung umsetzt.  



  Als reaktionsfähige Ester des Alkohols I  kann man beispielsweise einen     Halogenwasser-          stoffsäure-,    einen Schwefelsäure-, einen     Alkyl-          bz -.        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       II    entsprechenden     Amids.    Man kann aber  auch das freie     Amid        II    unter Zuhilfenahme  eines     Metallamids    als     Kondensationsmittel    mit,  einem reaktionsfähigen     Aminoalkoholester    zur  Reaktion bringen.  



  Das so erhaltene     Nicotinsäiue-N-        (1,2-di-          phenyl-äthyl)        -N-(2-pyrrolidino-äthyl)-amid     bildet ein farbloses Öl, welches unter 0,0 &  mm  bei 245 bis 250  siedet und sich gut in ver  dünnten Säuren, wenig in Wasser und     Petrol-          äther    löst. Das Chlorhydrat schmilzt aus     Me-          thyl-isobut.yl-keton,        umkristallisiert    bei 188  bis 190 . Die neue Verbindung soll als     Spas-          molytikum    und als Zwischenprodukt zur Her  stellung weiterer Derivate     Verwendung    fin  den.

    



       Beispiel.:     100g     Nicotinsäure-N-(1,2-diphenyl-äthyl)-          amid,    suspendiert in 350     cms        absol.    Benzol,  werden mit 18,5 g gepulvertem     Natriumamid     versetzt und kurze Zeit auf Siedetemperatur  erhitzt, wobei eine starke     Ammoniakentwick-          lung    eintritt.

   Nachdem die Gasentwicklung  nachgelassen hat, lässt man 46,5 g     2-Pyrroli-          dino--äthylchlorid,    gelöst in 300     em3        absol.     Benzol,     zutropfen    und rührt dann weitere 3,5  Stunden unter     Rückflusskochen.    Nach dem  Erkalten wird die Lösung vom überschüssigen       Natriumamid        abdekantiert    und mit 60  war  mer     1.5n-Salzsäure        ausgezogen,    bis der Aus-           zug    schwach sauer reagiert.

   Der noch warme  salzsaure Auszug wird mit Kohle filtriert       und    dann 2 Stunden in Eis gekühlt, wobei  das bei 188 bis 190  schmelzende Chlorhydrat  des     Nicotinsäure-N-(1,2-diphenyl-äthyl)-N-(2-          pyrrolidino-äthyl)-amids    in einer Ausbeute  von 65 % gewonnen wird.  



  Die aus der     wässrigen    Lösung mit verdünn:       ter    Lauge ausgefällte Base siedet unter 0,08 mm  bei 245 bis 250<B>0</B>.  



  An Stelle von     Natriumamid    als Konden  sationsmittel kann man das     Nicotinsäure-N-          (1,2-diphenyl-äthyl)-amid    mit Natrium be  handeln und das entstandene     Natriumsalz    an  schliessend mit     2-Pyrrolidino-äthylehlorid    kon  densieren, wobei die gleiche Verbindung in  befriedigender Ausbeute und Reinheit ge  wonnen wird.



      Process for the preparation of a new disubstituted nicotinic acid amide. The invention relates to a process for producing a new disubstituted nicotinic acid amide of the formula
EMI0001.0011
    which is characterized in that one has a reactive ester of the alcohol of the formula
EMI0001.0013
    With. one the rest
EMI0001.0014
    the supplying connection.



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



  It is advantageous to use an N-metal derivative of the amide corresponding to II as the compound supplying the radical II. But you can also bring the free amide II with the aid of a metal amide as a condensing agent, a reactive amino alcohol ester to react.



  The nicotinic acid-N- (1,2-diphenyl-ethyl) -N- (2-pyrrolidino-ethyl) -amide obtained in this way forms a colorless oil which boils below 0.0 & mm at 245 to 250 and is good Dissolves in dilute acids, little in water and petroleum ether. The chlorohydrate melts from methyl isobutyl ketone, recrystallized at 188-190. The new compound is intended to be used as a spasmodic and as an intermediate product for the manufacture of other derivatives.

    



       Example .: 100g nicotinic acid-N- (1,2-diphenyl-ethyl) - amide, suspended in 350 cms absol. Benzene, 18.5 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 evolution of gas has subsided, 46.5 g of 2-pyrrolidino ethyl chloride, dissolved in 300 em3 absol. Benzene, add dropwise and then stir under reflux for a further 3.5 hours. After cooling, the solution is decanted off from the excess sodium amide and extracted with 60 warmer 1.5N hydrochloric acid until the extract reacts slightly acidic.

   The still warm hydrochloric acid extract is filtered with charcoal and then cooled in ice for 2 hours, whereby the hydrochloric acid of nicotinic acid-N- (1,2-diphenyl-ethyl) -N- (2-pyrrolidino-ethyl) - which melts at 188 to 190 amides is obtained in a yield of 65%.



  The base precipitated from the aqueous solution with dilute alkali boils below 0.08 mm at 245 to 250 <B> 0 </B>.



  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 then condense with 2-pyrrolidino-ethyl chloride, the same compound being more satisfactory Yield and purity is obtained.

Claims (1)

PATENTANSPRUCH: Verfahren zur Herstellung eines neuen disubstituierten Nicotinsäureamids der Formel EMI0002.0014 dadurch gekennzeichnet, dass man einen reak tionsfähigen Ester des Alkohols der Formel EMI0002.0015 mit einer den Rest EMI0002.0016 liefernden Verbindung umsetzt. PATENT CLAIM: Process for the preparation of a new disubstituted nicotinic acid amide of the formula EMI0002.0014 characterized in that there is a reactive ester of the alcohol of the formula EMI0002.0015 with one the rest EMI0002.0016 the supplying connection. Das so erhaltene --\'ieotinsä.ure-N-(1,2-di- phenyl - ät hy 1) - N - (2-py rrolidino - äthyl) - amid bildet ein farbloses Öl, welches unter 0,08 mm bei 245 bis 250 siedet und sich leicht, in ver dünnten Säuren, wenig in Wasser und Pe- troläther löst. Die Verbindung soll als Spasmolytikum und als Zwischenprodukt Verwendung finden. The so obtained - \ 'ieotinsä.ure-N- (1,2-diphenyl - ät hy 1) - N - (2-pyrrolidino - ethyl) - amide forms a colorless oil, which is under 0.08 mm boils at 245 to 250 and dissolves easily in dilute acids, little in water and petroleum ether. The compound is said to be used as an antispasmodic and as an intermediate product. UNTERANSPR>\ CH Verfahren nach Patentansprueh, dadurch gekennzeichnet, dass man 2-Pyrrolidino-äthyl- chlorid in Gegenwart von. Natriumamid mit Nicotinsäure-N- (1, 2-dipheny 1-äthyl )-amid um setzt. SUBSTANTIAL APPLICATION> \ CH Method according to patent claim, characterized in that 2-pyrrolidino-ethyl chloride in the presence of. Sodium amide with nicotinic acid-N- (1, 2-dipheny 1-ethyl) amide sets.
CH297289D 1951-03-01 1951-03-01 Process for the preparation of a new disubstituted nicotinic acid amide. CH297289A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CH294511T 1951-03-01
CH297289T 1951-03-01

Publications (1)

Publication Number Publication Date
CH297289A true CH297289A (en) 1954-03-15

Family

ID=25733479

Family Applications (1)

Application Number Title Priority Date Filing Date
CH297289D CH297289A (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) CH297289A (en)

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