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DE955147C - Process for the production of new pharmacologically active oxydiamines - Google Patents

Process for the production of new pharmacologically active oxydiamines

Info

Publication number
DE955147C
DE955147C DEG10813A DEG0010813A DE955147C DE 955147 C DE955147 C DE 955147C DE G10813 A DEG10813 A DE G10813A DE G0010813 A DEG0010813 A DE G0010813A DE 955147 C DE955147 C DE 955147C
Authority
DE
Germany
Prior art keywords
oxydiamines
production
pharmacologically active
general formula
molecular weight
Prior art date
Legal status (The legal status 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 status listed.)
Expired
Application number
DEG10813A
Other languages
German (de)
Inventor
Dr Franz Haefliger
Dr Walter Schindler
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Novartis AG
Original Assignee
JR Geigy 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 JR Geigy AG filed Critical JR Geigy AG
Application granted granted Critical
Publication of DE955147C publication Critical patent/DE955147C/en
Expired legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
    • C07D295/125—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/13—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
    • C07D303/02—Compounds containing oxirane rings
    • C07D303/36—Compounds containing oxirane rings with hydrocarbon radicals, substituted by nitrogen atoms

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Hydrogenated Pyridines (AREA)

Description

Verfahren zur Herstellung neuer pharmakologisch wirksamer Oxydiamine Bei der Behandlung von psychischen Störungen spielen die Psychoplegica eine Rolle von zunehmender Wichtigkeit. Es wurde nun gefunden, daB eine Gruppe von neuen Oxydiaminen, die spasmolytische, antihistaminische und hypnotische Wirksamkeit besitzen, unter anderem auch wertvolle Psychoplegica sind, die sich zur Behandlung von psychischen Störungen und von schwerer vegetativer Dystonie eignen.Process for the production of new pharmacologically active oxydiamines The psychoplegics play a role in the treatment of mental disorders of increasing importance. It has now been found that a group of new oxydiamines which have spasmolytic, antihistaminic and hypnotic activity, among Other valuable psychoplegics are, which are used for the treatment of mental Disorders and severe vegetative dystonia.

Die neuen Oxydiamine, die auch als i-Diarylamino-3-amino-2-propanole bezeichnet werden können, entsprechen der allgemeinen Formel worin Am einen niedermolekularen Alkylamino- oder Dialkylaminorest, den Pyrrolidino- oder Piperidinorest, R, Wasserstoff oder eine niedermolekulare Alkyl-oder Alkoxygruppe, R2 eine niedermolekulare Alkyl-oder Alkoxygruppe bedeutet.The new oxydiamines, which can also be referred to as i-diarylamino-3-amino-2-propanols, correspond to the general formula where Am is a low molecular weight alkylamino or dialkylamino radical, the pyrrolidino or piperidino radical, R, hydrogen or a low molecular weight alkyl or alkoxy group, R2 is a low molecular weight alkyl or alkoxy group.

Man kann die erfindungsgemäßen Verbindungen herstellen, indem man ein Amin der allgemeinen Formel Am-H mit einem N-(2, 3-Epoxy-propyl)-diarylamin der allgemeinen Formel wobei Am, R, und R2 die oben gegebenen Bedeutungen haben, umsetzt. Die Umsetzung kann in An- oder Abwesenheit von Lösungsmitteln, vorzugsweise in der Wärme, durchgeführt werden. Je nach Reaktionsfähigkeit und Siedepunkt des verwendeten Amins bzw. Siedepunkt des verwendeten Lösungsmittels, wovon Äthanol und Methanol genannt seien, werden die Umsetzungen beispielsweise bei Siedetemperatur des Amins oder des Lösungsmittels unter Normaldruck, oder bei darüberliegenden Temperaturen im Autoklav vorgenommen.The compounds according to the invention can be prepared by combining an amine of the general formula Am-H with an N- (2,3-epoxypropyl) diarylamine of the general formula where Am, R, and R2 have the meanings given above. The reaction can be carried out in the presence or absence of solvents, preferably with heat. Depending on the reactivity and boiling point of the amine used or the boiling point of the solvent used, of which ethanol and methanol may be mentioned, the reactions are carried out, for example, at the boiling point of the amine or the solvent under normal pressure or at temperatures above this in the autoclave.

Als Ausgangsstoffe der Formel Am - H seien beispielsweise genannt: Methylamin, Äthylamin, n-Propylamin, n-Butylamin, Allylamin, Dimethylamin, Methyl-äthylamin, Diäthylamin, Di-n-propyl-amin, Diallylamin, Di-n-butylamin, Methyl-n-butylamin, Pyrrolidin und Piperidin.Examples of starting materials of the formula Am - H include: Methylamine, ethylamine, n-propylamine, n-butylamine, allylamine, dimethylamine, methylethylamine, Diethylamine, di-n-propylamine, diallylamine, di-n-butylamine, methyl-n-butylamine, Pyrrolidine and piperidine.

Als Epoxyverbindungen seien aufgezählt: die N - (2, 3 - Epoxy - propyl) - derivate von 2 - Methyldiphenylamin, 2, 2' - Dimethyldiphenylamin, 2 - Äthyldiphenylamin, z - Äthyl - 2' - methyldiphenylamin, z - Methoxydiphenylamin, 2, 2' - Dimethoxydiphenylamin, 2-Methyl-2'-methoxydiphenylamin, 2-Äthoxydiphenylamin und 2-Metliyl-z'-äthoxydiphenylamin. Diese N-(2, 3-Epoxy-propyl)-derivate können z. B. durch Umsetzung einer Alkahmetallverbindung, z. B. der Natrium- oder Lithiumverbindung der Diarylamine, mit Epichlorhydrin hergestellt werden.The following are listed as epoxy compounds: the N - (2, 3 - epoxy - propyl) - derivatives of 2 - methyldiphenylamine, 2, 2 '- dimethyldiphenylamine, 2 - ethyldiphenylamine, z - ethyl - 2 '- methyldiphenylamine, z - methoxydiphenylamine, 2, 2' - dimethoxydiphenylamine, 2-methyl-2'-methoxydiphenylamine, 2-ethoxydiphenylamine and 2-methyl-z'-ethoxydiphenylamine. These N- (2, 3-epoxy-propyl) derivatives can, for. B. by reacting an alkali metal compound, z. B. the sodium or lithium compound of diarylamines, made with epichlorohydrin will.

Die neuen Oxydiamine sind einsäurige Basen und bilden mit anorganischen und organischen Säuren Salze, von denen einige in Wasser leicht löslich sind.The new oxydiamines are mono-acidic bases and form with inorganic ones and organic acids salts, some of which are readily soluble in water.

Die nachfolgenden Beispiele erläutern die Herstellung erfindungsgemäßer Verbindungen. Teile bedeuten darin Gewichtsteile, diese verhalten sich zu Volumteilen wie g zu cm3. Die Temperaturen sind in Centigraden angegeben.The following examples explain the preparation of the invention Links. In it, parts mean parts by weight; these relate to parts by volume like g to cm3. Temperatures are given in centigrades.

Beispiel 1 N-(3-Pyrrolidino-2-oxy-propyl)-o, o'-ditolylamin-Hydrochlorid 4o Teile z, 2'-Dimethyl-diphenylamin und 25 Teile Epichlorhydrin werden in 300 Volumteilen absolutem Benzol gelöst. Dazu wird bei 4o bis 50° eine Suspension von lo Teilen Natriumamid in Toluol so zugetropft, daß die Temperatur konstant bleibt. Anschließend wird noch 16 Stunden unter Rückfluß gekocht. Man kühlt ab und nutscht durch ein mit etwas Kohle gedichtetes Filter. Dann wird die Benzollösung eingedampft und der ölige Rückstand in Äther aufgenommen, wobei etwas Harz ausfällt. Die ätherische Lösung wird mit Wasser gewaschen, getrocknet und eingedampft. Der Rückstand wird im Hochvakuum fraktioniert, wobei das N-(2, 3-Epoxy-propyl)-o, o'-ditolylamin bei 145 bis 1q.9° und o,2 mm übergeht.Example 1 N- (3-pyrrolidino-2-oxy-propyl) -o, o'-ditolylamine hydrochloride 40 parts of z, 2'-dimethyl-diphenylamine and 25 parts of epichlorohydrin are dissolved in 300 parts by volume of absolute benzene. To this end, a suspension of 10 parts of sodium amide in toluene is added dropwise at 40 ° to 50 ° in such a way that the temperature remains constant. The mixture is then refluxed for a further 16 hours. One cools down and sucks through a filter sealed with a little carbon. The benzene solution is then evaporated and the oily residue is taken up in ether, some resin precipitating out. The ethereal solution is washed with water, dried and evaporated. The residue is fractionated in a high vacuum, the N- (2,3-epoxy-propyl) -o, o'-ditolylamine passing over at 145 to 1q.9 ° and 0.2 mm.

16 Teile dieser Epoxyverbindung werden mit 3o Volumteilen Pyrrolidin 24 Stunden unter Rückfluß gekocht, der Basenüberschuß abdestilliert und der Rückstand in das Hydrochlorid übergeführt. F. z85°.16 parts of this epoxy compound with 30 parts by volume of pyrrolidine Boiled under reflux for 24 hours, the excess base was distilled off and the residue converted into the hydrochloride. F. z85 °.

In analoger Weise können hergestellt werden: N-(3-Diäthylamino-2-oxy-propyl)-o, o'-ditolylamin-Hydrochlorid, F.: 186 bis 187°; N-(3-Dimethylamino-2-oxy-propyl)-o, ö -ditolylamin-Hydrochlorid, F.: 216 bis 217°; N-(3-Piperidino-2-oxy-propyl)-o, o'- ditolylamin-Hydrochlorid, F.: 2o5 bis 2o6°; N- (3-Methylamino-2-oxypropyl) -o-äthyldiphenylamin-Hydrochlorid, N-(3-Äthylamino-2-oxypropyl)-o-methoxy-diphenylamin-Hydrochlorid, N-(3-Dimethylamino-z-oxypropyl)-o, ö -dimethoxydiphenylamin-Hydrochlorid, N-(3-Pyrrolidino-2-oxypropyl)-o-äthoxy-diphenylamin-Hydrochlorid.The following can be prepared in an analogous manner: N- (3-diethylamino-2-oxy-propyl) -o, o'-ditolylamine hydrochloride, m.p .: 186 to 187 °; N- (3-dimethylamino-2-oxy-propyl) -o, δ-ditolylamine hydrochloride, m .: 216 to 217 °; N- (3-piperidino-2-oxy-propyl) -o, o'-ditolylamine hydrochloride, F .: 2o5 to 2o6 °; N- (3-methylamino-2-oxypropyl) -o-ethyldiphenylamine hydrochloride, N- (3-ethylamino-2-oxypropyl) -o-methoxy-diphenylamine hydrochloride, N- (3-dimethylamino-z-oxypropyl) -o, ö -dimethoxydiphenylamine hydrochloride, N- (3-pyrrolidino-2-oxypropyl) -o-ethoxy-diphenylamine hydrochloride.

Claims (1)

PATENTANSPRUCH: Verfahren zur Herstellung neuer pharmakologisch wirksamer Oxydiamine der allgemeinen Formel worin Am einen niedermolekularen Alkylamino-oder Dialkylaminorest, den Pyrrolidino- ode Piperidinorest, R, Wasserstoff oder eine niedermolekulare Alkyl- oder Alkoxygruppe, R3 eine niedermolekulare Alkyl- oder Alkoxygruppe bedeutet, dadurch gekennzeichnet, daß man ein Amin der ällgemeinen Formel Am - H, worin Am die obige Bedeutung hat, mit einem 2, 3-Epoxy-propylamin der allgemeinen Formel . I RI R2 I@1 \ \N (;112-CH-CH, umsetzt. \0/
PATENT CLAIM: Process for the production of new pharmacologically active oxydiamines of the general formula in which Am is a low molecular weight alkylamino or dialkylamino group, the pyrrolidino or piperidino group, R, hydrogen or a low molecular weight alkyl or alkoxy group, R3 is a low molecular weight alkyl or alkoxy group, characterized in that an amine of the general formula Am - H, in which Am has the above meaning with a 2,3-epoxypropylamine of the general formula . I RI R2 I @ 1 \ \ N (; 112-CH-CH, implements. \ 0 /
DEG10813A 1952-01-25 1953-01-24 Process for the production of new pharmacologically active oxydiamines Expired DE955147C (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CH955147X 1952-01-25

Publications (1)

Publication Number Publication Date
DE955147C true DE955147C (en) 1956-12-27

Family

ID=4550291

Family Applications (1)

Application Number Title Priority Date Filing Date
DEG10813A Expired DE955147C (en) 1952-01-25 1953-01-24 Process for the production of new pharmacologically active oxydiamines

Country Status (1)

Country Link
DE (1) DE955147C (en)

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