CH343388A - Process for the preparation of new amides - Google Patents

Process for the preparation of new amides

Info

Publication number
CH343388A
CH343388A CH343388DA CH343388A CH 343388 A CH343388 A CH 343388A CH 343388D A CH343388D A CH 343388DA CH 343388 A CH343388 A CH 343388A
Authority
CH
Switzerland
Prior art keywords
sep
formula
alkylene
radical
preparation
Prior art date
Application number
Other languages
German (de)
Inventor
Henry Dr Phil Martin
Ernst Dr Phil Habicht
Original Assignee
Cilag Chemie Aktiengesellschaf
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 Chemie Aktiengesellschaf filed Critical Cilag Chemie Aktiengesellschaf
Publication of CH343388A publication Critical patent/CH343388A/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups

Description

  

  
 



  Verfahren zur Herstellung neuer Amide Es wurde gefunden, dass Amide der Formel
EMI1.1     


<tb> Ar-C <SEP> H-N- <SEP> C <SEP> 0-Alkylen-Am
<tb>  <SEP> R1
<tb> Ar-CH-R2
<tb>  in welcher Ar gegebenenfalls durch niederes Alkyl, Alkoxy und/oder Halogen substituiertes Phenyl,   R    Wasserstoff, Alkyl, Alkenyl oder Aralkyl, R2 Wasserstoff, Hydroxy, Alkoxy, Alkenoxy, Alkinoxy oder Aralkoxy und Am eine sekundäre oder tertiäre Aminogruppe bedeutet, als Antikonvulsantia verwendbar sind.



   Das vorliegende Patent bezieht sich auf ein Verfahren zur Herstellung der in Formel I definierten Amide.



   Das Verfahren ist dadurch gekennzeichnet, dass man ein Amin der Formel
EMI1.2     
 mit einer den Rest -CO-Alkylen-X abgebenden Verbindung, worin X einen durch eine sekundäre oder tertiäre Aminogruppe ersetzbaren Rest bedeutet. umsetzt und die erhaltene Verbindung der Formel
EMI1.3     
 mit einem primären oder sekundären Amin zur Reaktion bringt. Anschliessend können die so erhaltenen Amide, falls dies erwünscht, in ihre Säureadditionssalze überführt werden.



   Als den Rest -CO-Alkylen-X abgebende Verbindung kann man verwenden: eine entsprechende Säure, ein Halogenid oder ein Anhydrid einer solchen Säure.



   Der Rest X kann ein Halogenatom oder eine   Alk-yl-SO,O-    bzw.   ArylO2O-Gruppe    darstellen; durch Umsetzen eines Acylderivates der Formel III mit einem primären oder sekundären Amin erhält man ein Amid der Formel I.



   Als Amine der Formel III kann man beispielsweise verwenden:   : l-Amino-1, 2-diphenyl-äthan,       1 -Hydroxy-2-amino- 1 ,2-diphenyl-äthan, 1-Methoxy-    2-amino-1   ,2-diphenyl-äthan,      l-(4'-Methoxy-phenyl)-       2-phenyl-l-amino- äthan, 1-(4' -Chlor- phenyl)-2 phenyl- 1 -amino-äthan, 1 - (4'-Chlor-phenyl) 2-phenyl-    2-amino-äthan usw.



   Diese Amine kann man beispielsweise mit Hilfe der folgenden Säurederivate in die Acylderivate der Formel III überführen:   Chloressigsäurechlorid,    a   Chlor- propionsäurechlorid, fl - Chlor - propionsäure    chlorid, a-Brom-buttersäurebromid usf.



   Die so erhaltenen Acylderivate der Formel III kann man beispielsweise mit den folgenden Aminen umsetzen: Butylamin, Allylamin, Benzylamin, Dimethylamin, Diäthylamin, Dipropylamin, Dibutylamin, Methylbenzylamin, Methylpropylamin, Methylbutylamin, Butylbenzylamin, Morpholin, Piperidin, Pyrrolidin, C-alkylierte Piperidine oder Pyrrolidine, N-Alkyl-piperazine usf.



   Beispiel
1 Mol   1,2-Diphenyl-äthylamin    wird in der dreifachen Menge Aceton gelöst. Zu der Lösung gibt man 1 Mol fein pulverisiertes Kaliumcarbonat und lässt zu dem Ganzen unter Rühren 1,1 Mol   Chloressigsäure-    chlorid zutropfen. Nach 3 Stunden giesst man auf Eis, saugt das N-Chloressigsäure-(l   2-diphenyl-äthyl)-     amid ab, löst dieses in der dreifachen Menge Methanol und versetzt mit 2 Mol Diäthylamin. Die Reaktionsmischung wird im Autoklaven 4 Stunden auf   1200    C erhitzt. Nach dem Aufarbeiten erhält man das   Diäthylaminoessigsäure-1,    ,2-diphenyl-äthylamid vom Smp. 940 C. Das Hydrochlorid der Base schmilzt bei   145     C, das N-Methylmethansulfonat bei   97"    C.



   In gleicher Weise, wie im vorstehenden Beispiel beschrieben, gewinnt man die folgenden Amide der Formel
EMI2.1     

EMI2.2     


<tb>  <SEP> N-Methyl
<tb>  <SEP> R1 <SEP> Am <SEP> Base <SEP> Smp. <SEP> oder <SEP> Sdp. <SEP> ! <SEP> Hydrochlorid <SEP> methansulfonat
<tb>  <SEP> Smp. <SEP> Smp.
<tb>



   <SEP> .CH3
<tb>  <SEP> H <SEP> -N <SEP> 91"C <SEP> 171-172"C <SEP> 146-147"C
<tb>  <SEP> CH3
<tb>  <SEP> /CH3
<tb> CH3 <SEP> -N <SEP> 0,05: <SEP> 158-160"C <SEP> 187-188"C <SEP> 135-136"C
<tb>  <SEP> CH3
<tb>  <SEP> /C2H5
<tb> CH3 <SEP> -N <SEP> 0,15: <SEP> 1700C <SEP> 140"C <SEP> 133"C
<tb>  <SEP> C2H5
<tb>  <SEP> H-NS <SEP> 124-125"C <SEP> 1800C <SEP> 102-103"C
<tb> CH, <SEP> H <SEP> | <SEP> 0,07: <SEP> 175"C <SEP> 196"C <SEP> 80"C
<tb>  <SEP> yCH5
<tb>  <SEP> H <SEP> C2Hs <SEP> -N <SEP> 04 <SEP> : <SEP> 207  <SEP> C <SEP> 800 <SEP> c <SEP> 121 <SEP> 125  <SEP> C
<tb>  <SEP> 0,04: <SEP> 2070 <SEP> C
<tb>  <SEP> C2H0
<tb>  <SEP> yCH3
<tb>  <SEP> H <SEP> -N <SEP> 66-67"C <SEP> 113-114"C <SEP> 790C
<tb>  <SEP> C3H7 <SEP> (n)
<tb>  <SEP> CH5
<tb>  <SEP> H <SEP> CH2 <SEP> (n) <SEP> 0, <SEP> 01 <SEP> 61-62"C <SEP> C <SEP> 136-137"C <SEP> 96-97"C
<tb>  <SEP> 0,01:

   <SEP> l971990 <SEP> C
<tb>  <SEP> C4H9(n)
<tb>    



  
 



  Process for the preparation of new amides It has been found that amides of the formula
EMI1.1


<tb> Ar-C <SEP> H-N- <SEP> C <SEP> 0-alkylene-Am
<tb> <SEP> R1
<tb> Ar-CH-R2
<tb> in which Ar is phenyl optionally substituted by lower alkyl, alkoxy and / or halogen, R is hydrogen, alkyl, alkenyl or aralkyl, R2 is hydrogen, hydroxy, alkoxy, alkenoxy, alkynoxy or aralkoxy and Am is a secondary or tertiary amino group, as Anticonvulsants are usable.



   The present patent relates to a process for the preparation of the amides defined in Formula I.



   The process is characterized in that an amine of the formula
EMI1.2
 with a compound releasing the radical -CO-alkylene-X, in which X is a radical which can be replaced by a secondary or tertiary amino group. and the resulting compound of the formula
EMI1.3
 reacts with a primary or secondary amine. The amides thus obtained can then, if so desired, be converted into their acid addition salts.



   As a compound donating the radical -CO-alkylene-X one can use: a corresponding acid, a halide or an anhydride of such an acid.



   The radical X can represent a halogen atom or an alk-yl-SO, O or arylO2O group; by reacting an acyl derivative of the formula III with a primary or secondary amine, an amide of the formula I is obtained.



   The following amines of the formula III can be used, for example: 1-amino-1, 2-diphenyl-ethane, 1-hydroxy-2-amino-1, 2-diphenyl-ethane, 1-methoxy-2-amino-1, 2 -diphenyl-ethane, 1- (4'-methoxyphenyl) -2-phenyl-1-amino-ethane, 1- (4 '-chlorophenyl) -2 phenyl- 1 -amino-ethane, 1- (4 '-Chloro-phenyl) 2-phenyl-2-amino-ethane etc.



   These amines can be converted into the acyl derivatives of the formula III, for example, with the aid of the following acid derivatives: chloroacetic acid chloride, a chloropropionic acid chloride, fl-chloro-propionic acid chloride, a-bromobutyric acid bromide, etc.



   The acyl derivatives of the formula III obtained in this way can, for example, be reacted with the following amines: butylamine, allylamine, benzylamine, dimethylamine, diethylamine, dipropylamine, dibutylamine, methylbenzylamine, methylpropylamine, methylbutylamine, butylbenzylamine, morpholine, piperidine, pyrrolidine, C-alkylated piperidines , N-alkyl-piperazines, etc.



   example
1 mol of 1,2-diphenylethylamine is dissolved in three times the amount of acetone. 1 mol of finely powdered potassium carbonate is added to the solution and 1.1 mol of chloroacetic acid chloride is added dropwise to the whole with stirring. After 3 hours, the mixture is poured onto ice, the N-chloroacetic acid (l 2-diphenylethyl) amide is filtered off with suction, this is dissolved in three times the amount of methanol and 2 moles of diethylamine are added. The reaction mixture is heated to 1200 ° C. for 4 hours in an autoclave. After working up, 1, 2-diphenylethylamide diethylaminoacetic acid with a melting point of 940 ° C. is obtained. The hydrochloride of the base melts at 145 ° C., the N-methyl methanesulfonate at 97 ° C.



   The following amides of the formula are obtained in the same way as described in the previous example
EMI2.1

EMI2.2


<tb> <SEP> N-methyl
<tb> <SEP> R1 <SEP> Am <SEP> Base <SEP> Smp. <SEP> or <SEP> Sdp. <SEP>! <SEP> hydrochloride <SEP> methanesulfonate
<tb> <SEP> Smp. <SEP> Smp.
<tb>



   <SEP> .CH3
<tb> <SEP> H <SEP> -N <SEP> 91 "C <SEP> 171-172" C <SEP> 146-147 "C
<tb> <SEP> CH3
<tb> <SEP> / CH3
<tb> CH3 <SEP> -N <SEP> 0.05: <SEP> 158-160 "C <SEP> 187-188" C <SEP> 135-136 "C
<tb> <SEP> CH3
<tb> <SEP> / C2H5
<tb> CH3 <SEP> -N <SEP> 0.15: <SEP> 1700C <SEP> 140 "C <SEP> 133" C
<tb> <SEP> C2H5
<tb> <SEP> H-NS <SEP> 124-125 "C <SEP> 1800C <SEP> 102-103" C
<tb> CH, <SEP> H <SEP> | <SEP> 0.07: <SEP> 175 "C <SEP> 196" C <SEP> 80 "C
<tb> <SEP> yCH5
<tb> <SEP> H <SEP> C2Hs <SEP> -N <SEP> 04 <SEP>: <SEP> 207 <SEP> C <SEP> 800 <SEP> c <SEP> 121 <SEP> 125 <SEP > C
<tb> <SEP> 0.04: <SEP> 2070 <SEP> C
<tb> <SEP> C2H0
<tb> <SEP> yCH3
<tb> <SEP> H <SEP> -N <SEP> 66-67 "C <SEP> 113-114" C <SEP> 790C
<tb> <SEP> C3H7 <SEP> (n)
<tb> <SEP> CH5
<tb> <SEP> H <SEP> CH2 <SEP> (n) <SEP> 0, <SEP> 01 <SEP> 61-62 "C <SEP> C <SEP> 136-137" C <SEP> 96 -97 "C
<tb> <SEP> 0.01:

   <SEP> l971990 <SEP> C
<tb> <SEP> C4H9 (n)
<tb>

Claims (1)

PATENTANSPRUCH Verfahren zur Herstellung neuer Amide der Formel EMI2.3 <tb> Ar-CH-N-CO-Alkylen-Am <tb> <SEP> R1 <tb> Ar-CH-R2 <tb> in welcher Ar gegebenenfalls durch niederes Alkyl, Alkoxy und/oder Halogen substituiertes Phenyl, R Wasserstoff, Alkyl, Alkenyl oder Aralkyl, R2 Wasserstoff, Hydroxy, Alkoxy, Alkenoxy, Alkinoxy oder Aralkoxy und Am eine sekundäre oder tertiäre Aminogruppe bedeutet, dadurch gekennzeichnet, dass man ein Amin der Formel EMI2.4 mit einer den Rest -CO-Alkylen-X abgebenden Verbindung, worin X einen durch eine sekundäre oder tertiäre Aminogruppe ersetzbaren Rest bedeutet, umsetzt und die erhaltene Verbindung der Formel EMI3.1 <tb> Ar-CH-N- <SEP> C <SEP> O-Alkylen-X <tb> <SEP> R1 <SEP> III <tb> Ar-CH-R2 <tb> mit einem primären oder sekundären Amin zur Reaktion bringt. PATENT CLAIM Process for the production of new amides of the formula EMI2.3 <tb> Ar-CH-N-CO-alkylene-Am <tb> <SEP> R1 <tb> Ar-CH-R2 <tb> in which Ar is phenyl optionally substituted by lower alkyl, alkoxy and / or halogen, R is hydrogen, alkyl, alkenyl or aralkyl, R2 is hydrogen, hydroxy, alkoxy, alkenoxy, alkynoxy or aralkoxy and Am is a secondary or tertiary amino group, thereby characterized in that one is an amine of the formula EMI2.4 with a compound releasing the radical -CO-alkylene-X, in which X is a radical which can be replaced by a secondary or tertiary amino group, and the resulting compound of the formula EMI3.1 <tb> Ar-CH-N- <SEP> C <SEP> O-alkylene-X <tb> <SEP> R1 <SEP> III <tb> Ar-CH-R2 <tb> with a primary or secondary amine to react.
CH343388D 1956-03-09 1956-03-09 Process for the preparation of new amides CH343388A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CH343388T 1956-03-09

Publications (1)

Publication Number Publication Date
CH343388A true CH343388A (en) 1959-12-31

Family

ID=4506513

Family Applications (1)

Application Number Title Priority Date Filing Date
CH343388D CH343388A (en) 1956-03-09 1956-03-09 Process for the preparation of new amides

Country Status (1)

Country Link
CH (1) CH343388A (en)

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4769466A (en) * 1987-02-06 1988-09-06 Pennwalt Corporation 2-aminoacetamide pyridinyl derivatives
US4798687A (en) * 1987-02-06 1989-01-17 Pennwalt Corporation 2-Amino-N-[1,2-Diphenyl-1-(thifluoromethyl)ethyl]acetamide derivatives
US4871872A (en) * 1988-01-20 1989-10-03 Fisons Corporation 2-[(2-aminoacetyl)amino]acetamide derivatives
EP0356035A2 (en) * 1988-08-12 1990-02-28 Astra Aktiebolag Arylkalkyl-amines and -amides having anticonvulsant and neuroprotective properties
US5047541A (en) * 1987-02-06 1991-09-10 Fisons Corporation 2-azacyclocarboxamide derivatives
US5093524A (en) * 1990-10-15 1992-03-03 Fisons Corporation 2-(alkylamino)acetamide derivatives
US5331007A (en) * 1987-02-06 1994-07-19 Fisons Corporation Arylalkyl-amines and -amides having anticonvulsant and neuroprotective properties
US5382683A (en) * 1988-01-20 1995-01-17 Fisons Corporation 2-aminopropanamide derivatives
US5430044A (en) * 1987-02-06 1995-07-04 Fisons Corporation Arylalkyl-amines and -amides having anticonvulsant and neuroprotective properties

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5331007A (en) * 1987-02-06 1994-07-19 Fisons Corporation Arylalkyl-amines and -amides having anticonvulsant and neuroprotective properties
US4798687A (en) * 1987-02-06 1989-01-17 Pennwalt Corporation 2-Amino-N-[1,2-Diphenyl-1-(thifluoromethyl)ethyl]acetamide derivatives
US5605916A (en) * 1987-02-06 1997-02-25 Astra Ab Arylalkyl-amines having anticonvulsant and neuroprotective properties
US5539120A (en) * 1987-02-06 1996-07-23 Griffith; Ronald C. Arylalkyl-amines having anticonvulsant and neuroprotective properties
US5430044A (en) * 1987-02-06 1995-07-04 Fisons Corporation Arylalkyl-amines and -amides having anticonvulsant and neuroprotective properties
US4769466A (en) * 1987-02-06 1988-09-06 Pennwalt Corporation 2-aminoacetamide pyridinyl derivatives
US5047541A (en) * 1987-02-06 1991-09-10 Fisons Corporation 2-azacyclocarboxamide derivatives
US5382683A (en) * 1988-01-20 1995-01-17 Fisons Corporation 2-aminopropanamide derivatives
US4871872A (en) * 1988-01-20 1989-10-03 Fisons Corporation 2-[(2-aminoacetyl)amino]acetamide derivatives
WO1991011995A1 (en) * 1988-08-12 1991-08-22 Fisons Corporation Arylalkyl-amines and -amides having anticonvulsant and neuroprotective properties
EP0356035A3 (en) * 1988-08-12 1991-04-03 Astra Aktiebolag Arylkalkyl-amines and -amides having anticonvulsant and neuroprotective properties
EP0356035A2 (en) * 1988-08-12 1990-02-28 Astra Aktiebolag Arylkalkyl-amines and -amides having anticonvulsant and neuroprotective properties
US5093524A (en) * 1990-10-15 1992-03-03 Fisons Corporation 2-(alkylamino)acetamide derivatives

Similar Documents

Publication Publication Date Title
CH343388A (en) Process for the preparation of new amides
DE955508C (en) Process for the preparation of anticonvulsant carboxamides
DE3039571C2 (en)
DE766207C (en) Process for the preparation of basic compounds of the diarylmethane series
DE1046063B (en) Process for the production of new, amoebicidal acetanilides
AT206890B (en) Process for the preparation of new tertiary amines
AT260914B (en) Process for the preparation of new α- (aminoalkoxyphenyl) -α&#39;-nitrostilbenes and their acid addition salts or quaternary ammonium compounds
AT226679B (en) Process for the production of new o-phenylenediamines
AT201586B (en) Process for the preparation of new aryloxyacetic acid amides
DE2655794A1 (en) Prepn. of ethylene cyanohydrin from acrylonitrile and water - in presence of quat. ammonium hydroxide catalyst and formaldehyde, for use in prepn. of pharmaceuticals, plant protection agents, dyes, etc.
AT218513B (en) Process for the preparation of new basic amides o, o&#39;-disubstituted benzoic acids, their salts and quaternary ammonium compounds
AT202125B (en) Process for the preparation of new α-mercapto acid amides
AT223189B (en) Process for the preparation of new aryloxyacetic acid amides
AT162899B (en) Process for the preparation of new aminoalkyl ethers of alcohols of the aromatic-aliphatic series
AT229873B (en) Process for the preparation of 1,4-disubstituted piperazine derivatives
AT201605B (en) Process for the preparation of the new α, α -diphenyl-γ-hexamethyleneiminobutyramide
AT254868B (en) Process for the preparation of new disubstituted isoxazole compounds
AT256823B (en) Process for the preparation of new heterocyclic benzamido compounds and their salts
AT222104B (en) Process for the preparation of new cyclobutane derivatives
AT233543B (en) Process for the production of new tertiary amines or quaternary ammonium compounds
AT238186B (en) Process for the preparation of new pyrrolidine compounds
AT231439B (en) Process for the preparation of new o-alkoxybenzoic acid aminoalkylamides
AT268256B (en) Process for the preparation of new 2-alkoxy-5-halobenzoic acid esters substituted in the 4-position
AT313298B (en) Process for the production of new pyrrolidine-N-carboxylic acid haloanilides
AT250326B (en) Process for the preparation of new N-substituted 1-phenyl-2-aminopropanes and their non-toxic acid addition salts