CH297290A - 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
CH297290A
CH297290A CH297290DA CH297290A CH 297290 A CH297290 A CH 297290A CH 297290D A CH297290D A CH 297290DA CH 297290 A CH297290 A CH 297290A
Authority
CH
Switzerland
Prior art keywords
nicotinic acid
amide
preparation
acid amide
pyrrolidino
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 CH297290A publication Critical patent/CH297290A/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 Herstellung eines neuen     disiibstituier-          ten        Nicotinsäureamids    der Formel  
EMI0001.0008     
    welches dadurch gekennzeichnet ist, dass man  einen reaktionsfähigen Ester des Alkohols der  Formel  
EMI0001.0009     
    mit einer den Rest  
EMI0001.0010     
         liefernden    Verbindung umsetzt.  



  Als reaktionsfähige Ester des Alkohols I  kann man     beispielsweise    einen Halogenwasser  stoffsäure-, einen Schwefelsäure-, einen     Alkyl-          bzw.        Arvlsulfonsäureester    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     Aminoälkoholester    zur Re  aktion bringen.  



  Das so erhaltene     Nicot.insäure-N-(1,2-di-          plienyl-äthyl)-N-        (3-pyrrolidino-propyl)-amid     bildet ein farbloses Öl, welches unter 0,08 mm  bei 250 bis 255  siedet und sich gut in ver  dünnten Säuren, wenig in Wasser und     Pe-          troläther    löst. Das Chlorhydrat     schmilzt    aus       Methyl-isobutyl-keton,    umkristallisiert bei 127  bis 130 . Die neue Verbindung soll als     Spas-          molytikiim    und als Zwischenprodukt zur Her  stellung weiterer Derivate Verwendung fin  den.  



       Beispiel:     100 g     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 51,5 g     3-Pyrro-          lidino-propylchlorid,    gelöst in 300     cm3        absol.     Benzol,     zutropfen    und rührt dann weitere  4 Stunden unter     Rückflusskochen.    Nach dem  Erkalten wird die Lösung vom überschüssigen       Natriumamid        abdekantiert    und mit 60  war  mer     1,5n-Salzsäure    ausgezogen, bis der Auszug      schwach sauer reagiert.

   Der noch warme salz  saure Auszug wird mit Kohle filtriert und  dann 1,5 Stunden in Eis gekühlt, wobei das  bei 127 bis 130  schmelzende Chlorhydrat des       Nieotinsäure-N-        (1,2-diphenyl-äthyl)    -N-     (3-          pyrrolidino-prop.#-1)-amids    in einer Ausbeute  von 60 % gewonnen wird.  



  Die aus der     wässrigen    Lösung mit verdünn  ter Lauge ausgefällte Base siedet unter 0,08 mm  bei 250 bis 255 .  



  An Stelle von     Natritunamid    als Konden  sationsmittel kann man das N     icotinsä-Lire-N-          (1,2-diphenyl-äthyl)-amid    mit Natrium be  handeln und das entstandene N     atriumsalz    an  schliessend mit     3-Pyrrolidino-propylehlorid     kondensieren, wobei die gleiche Verbindung in  befriedigender Ausbeute und Reinheit gewon  nen wird.



      Process for the preparation of a new disubstituted nicotinic acid amide. The invention relates to a process for the production of a new disubstituted nicotinic acid amide of the formula
EMI0001.0008
    which is characterized in that one has a reactive ester of the alcohol of the formula
EMI0001.0009
    with one the rest
EMI0001.0010
         the supplying connection.



  The reactive ester of the alcohol I can be, for example, a hydrogen halide, a sulfuric acid, an alkyl or Arvlsulfonsäureester. 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 with a reactive amino alcohol ester to re action.



  The nicotinic acid-N- (1,2-di-plienyl-ethyl) -N- (3-pyrrolidino-propyl) -amide obtained in this way forms a colorless oil which boils below 0.08 mm at 250 to 255 and becomes Dissolves well in diluted acids, little in water and petroleum ether. The chlorohydrate melts from methyl isobutyl ketone, recrystallized at 127 to 130. The new compound is intended to be used as a spasmolytikiim and as an intermediate product for the manufacture of further derivatives.



       Example: 100 g of 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 the boiling point for a short time, during which a strong evolution of ammonia occurs.

   After the evolution of gas has subsided, 51.5 g of 3-pyrrolidino-propyl chloride, dissolved in 300 cm3 of absol. Benzene, add dropwise and then stir under reflux for a further 4 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 1.5 hours, whereby the chlorohydrate of nieotinic acid-N- (1,2-diphenyl-ethyl) -N- (3-pyrrolidino-, which melts at 127 to 130) prop. # - 1) -amids is obtained in a yield of 60%.



  The base precipitated from the aqueous solution with dilute lye boils below 0.08 mm at 250 to 255.



  Instead of Natritunamid as a condensation agent, you can treat the Nicotinsä-Lire-N- (1,2-diphenyl-ethyl) -amide with sodium and then condense the resulting sodium salt with 3-pyrrolidino-propyl chloride, the same Compound in satisfactory yield and purity is won.

Claims (1)

PATENTANSPRU CH Verfahren zur Herstellung eines neuen disubstituierten Nicotinsäureamids der Formel EMI0002.0015 dadurch gekennzeichnet., dass man einen reak tionsfähigen Ester des Alkohols der Formel EMI0002.0016 mit einer den Rest EMI0002.0017 liefernden Verbindung umsetzt. Das so erhaltene Nicotinsäiire-N-(1,2-di- phenyl-äthyl)-N- (3-pyrrolidino-propyl)-amid bildet ein farbloses Öl, welches unter 0,08 mm bei 250 bis 255 siedet und sich leicht in ver dünnten Säuren, wenig in Wasser und Petrol- äther löst. PATENT APPLICATION Process for the preparation of a new disubstituted nicotinic acid amide of the formula EMI0002.0015 characterized in that one has a reactive ester of the alcohol of the formula EMI0002.0016 with one the rest EMI0002.0017 the supplying connection. The nicotinic acid-N- (1,2-diphenyl-ethyl) -N- (3-pyrrolidino-propyl) -amide obtained in this way forms a colorless oil which boils below 0.08 mm at 250 to 255 and easily dissolves in diluted acids, little dissolves in water and petroleum ether. Die Verbindung soll als Spasmolyt.ikum und als Zwischenprodukt Verwendung finden. UNTERANSPRUCH: . Verfahren nach Patentanspx-Lich, dadurch gekennzeichnet, dass man 3-Pyrrolidino-pro- pylchlorid in Gegenwart von Natriumamid mit Nicotinsäure-N-(1,2-diphenyl-äthyl)-amid umsetzt. The compound is said to be used as an antispasmodic and as an intermediate product. SUBClaim:. Process according to patent application Lich, characterized in that 3-pyrrolidino-propyl chloride is reacted with nicotinic acid-N- (1,2-diphenyl-ethyl) -amide in the presence of sodium amide.
CH297290D 1951-03-01 1951-03-01 Process for the preparation of a new disubstituted nicotinic acid amide. CH297290A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CH294511T 1951-03-01
CH297290T 1951-03-01

Publications (1)

Publication Number Publication Date
CH297290A true CH297290A (en) 1954-03-15

Family

ID=25733480

Family Applications (1)

Application Number Title Priority Date Filing Date
CH297290D CH297290A (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) CH297290A (en)

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