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DE1545780A1 - Process for the preparation of substituted benzimidazole derivatives - Google Patents

Process for the preparation of substituted benzimidazole derivatives

Info

Publication number
DE1545780A1
DE1545780A1 DE19651545780 DE1545780A DE1545780A1 DE 1545780 A1 DE1545780 A1 DE 1545780A1 DE 19651545780 DE19651545780 DE 19651545780 DE 1545780 A DE1545780 A DE 1545780A DE 1545780 A1 DE1545780 A1 DE 1545780A1
Authority
DE
Germany
Prior art keywords
general formula
group
preparation
phenyl
piperidino
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.)
Pending
Application number
DE19651545780
Other languages
German (de)
Inventor
Mehes Dr Med Gyula
Hideg Dr Kalman
Hideg Dr Geb Hankowsky Kalman
Desci Dr Med Laszlo
Karmos Gyoergy Dr Med Varszegi
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.)
Egyt Gyogyszervegyeszeti Gyar
Original Assignee
Egyt Gyogyszervegyeszeti Gyar
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 Egyt Gyogyszervegyeszeti Gyar filed Critical Egyt Gyogyszervegyeszeti Gyar
Publication of DE1545780A1 publication Critical patent/DE1545780A1/en
Pending legal-status Critical Current

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D235/00Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/06Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D235/00Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/18Benzimidazoles; Hydrogenated benzimidazoles with aryl radicals directly attached in position 2

Landscapes

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

Description

Beschreibungdescription

zu der
Patentanmeldung Γ
to the
Patent application Γ

der Firmaof the company

EGYBSÜM GYOGYSZBR- es TAPSZBRGZAR n) Budapest X, Kereszturi ut 30-38 (Ungarn;EGYBSÜM GYOGYSZBR- es TAPSZBRGZAR n) Budapest X, Kereszturi ut 30-38 (Hungary;

betreffendconcerning

Verfahren zur Herstellung von susbstituierten BenzimidazolderivatenProcess for the preparation of substituted Benzimidazole derivatives

Der Gegenstand der Erfindung ist ein Verfahren zur Herstellung von neuen, substituierten Sensimidazol· derivaten der allgemeinen Formel IThe object of the invention is a process for the preparation of new, substituted sensimidazole derivatives of the general formula I

worin R1 für Waeserötoff oder für eine Phenyl·, Methoxyphenyl-, (Primethoxyphenyl-, Puryl-, Pyridiyl- oder Aethylpjrrldylgruppe, Rg tür eine Dia,6thyl*mino-r wherein R 1 is a phenyl or Waeserötoff ·, methoxyphenyl, (Primethoxyphenyl-, Puryl-, Pyridiyl- or Aethylpjrrldylgruppe, R g door, a slide, 6thyl mino- * r

■ " ^ ' 7 BAD ORIGINAL■ "^ '7 BAD ORIGINAL

62/5962/59

009816/185t009816 / 185t

Diäthylaftino-, Morpholine-j Piperidino- ode* Pyrrolidinogruppe stehen, wobei aber in Fällen,- nenn R. eine Phenyl- oder Methoxyphenylgruppe bedeutet, R-keine Dirnethylamino- oder Piperidinogruppe sein kann* η β 2 oder 3.Diethylaftino, morpholine-j piperidino or * pyrrolidino group stand, but in cases - call R. denotes a phenyl or methoxyphenyl group, R-denotes none Can be dirnethylamino or piperidino * η β 2 or 3.

Diese auf das zentrale Nervensystem wirkende neue Benzimidazolderivate werden erfindungegemäsa derart hergestellt, dass man Benzimidazole der allgemeinen Formel II These new benzimidazole derivatives, which act on the central nervous system, are made according to the invention prepared in such a way that benzimidazoles of the general formula II

in an sioh bekannter Weise mit Aminoalkylenhalogenide 4er allgemeinen »owwl IIIin a manner known per se with aminoalkylene halides 4 general »owwl III

X - <CH2)n - R2 IIIX - <CH 2 ) n - R 2 III

kondensiert: in diesen Formeln steht J fü» ein Halo» genatom, während R1, R2 und η die obige Bedeutung haben» Die Kondensation wird in einem organischen Lösungsmittel , ZtB. in Benzolr zweokaässig in Anwesenheit eines Kondensationsmittels durchgeführt\ als Kondensationsmittel können Alkali- oder Erdalkalimetalle, deren Amide, Hydride, Oxyde oder Alkoholate angewendet werden* Die Ausgangsstoffe der Synthese können nach bekannten Methoden hergestellt werden«condensed: in these formulas J stands for a halogen atom, while R 1 , R 2 and η have the above meaning “The condensation takes place in an organic solvent, ZtB. in benzene r zweokaässig in the presence of a condensing agent performed \ as a condensing agent can alkali or alkaline earth metals, their amides, hydrides, oxides or alkoxides are applied * The starting materials of the synthesis can be prepared by known methods "

Die erfindungsgemäss hergeetellten neuen Verindungen bilden mit Säuren waeeer lös Hohe, t he rape-The new compounds produced according to the invention form water-soluble high, temperature-rape-

BADBATH

0098167188t0098167188t

utiseh anwendbare Salze. Als selche salzbildende Säuren können 3.3» Salzsäure, Bromwasseratoffeänre, Schwefelsäure. Salpetersäure, Phosphorsäure, Essigsäure, Apfelsäure, Zimtsäure etc angewendet werden. Die neuen Basen bilden ferner mit Alkylhalogtniden, bei Kochen unter Rttekf lues in polaren Lösungemitteln (z.B. in Aceton oder in einem Alkohol) oder fcei längerem Stehen auch bei Zimmertemperatur, quaternäre Salze.useful salts. As a salt-forming one Acids can 3.3 »hydrochloric acid, hydrobromic acid, Sulfuric acid. Nitric acid, phosphoric acid, acetic acid, Malic acid, cinnamic acid etc. can be used. The new bases also form with alkyl halides, when boiling under Rttekf lues in polar solvents (e.g. in acetone or in an alcohol) or longer Standing even at room temperature, quaternary salts.

Die erfindungsgemäss herstellbaren neuen Verbindungen zeigen verschiedene, bei BenzimidasoMerivaten bisher nicht bekannte Wirkungen auf das zentrale Nervensystem. Sie hemmen u.a. die Sekretion von Magensäure und !-fagensäften. Ein Teil dieser Verbindungen,- vor allem die am Stickstoffatom duroh eine Hydroxy. alkyl~8citenket te substituierten Derivate, haben sedative Wirkung. Diese Verbindungen aeigen keine, für Benzyl-benzimidazole übrigens charakteristische atiaungsdepressante Y/irkung, vielmehr treten bei diesen Verbindungen atmungserregende und zentralerregende Wirkungen· auf.The novel compounds which can be prepared according to the invention show various types of benzimidaseo derivatives previously unknown effects on the central nervous system. Among other things, they inhibit the secretion of Gastric acid and gastric juices. Some of these compounds - especially those on the nitrogen atom duroh one Hydroxy. alkyl-8cite chain substituted derivatives, have a sedative effect. These connections aeigen none, by the way, characteristic of benzylbenzimidazoles Atiaungsdepressante Y / ffekt, rather kicking respiratory and central excitation in these compounds Effects on.

Die erfiniu'i£sgem£s8 herstellbaren Verbindungen können a.i sich oder mit weiteren therapeutisch wirkenden Verbindungen kombiniert, unter Anwendung der üblichen pharmazeutischen Hilfsstoffe und pharmazeutischen Herstellungsverfahren zu gebrauchsfertigen Arzneimittelpräparaten verarbeitet werden.The erfiniu'i £ sgem £ s8 establishable connections can a.i itself or combined with other therapeutically active compounds, using the usual pharmaceutical excipients and pharmaceutical Manufacturing processes are processed into ready-to-use pharmaceutical preparations.

- 3 - BAD ORfQINAL- 3 - BAD ORfQINAL

009816/18B>009816 / 18B>

Das erfindungsgemässe Verfahren wird durch das nachstehende Beispiel näher veranschaulicht.The inventive method is through the the following example is illustrated in more detail.

Beispiel Example l

19,52 g (0,1 Mol) 2-Qi-Pyridyl)--benziraidazol und 11,2 g (0,2 Hol) frisch gepulvertes Kaliumhydroxyd werden in 200 ml trockenem 3enzol suspendiert und mit einer Lösung von 13,6 g (o,l Mol) N-(i'"-Chl6rEthyl)- -diäthylamin-Base in 50 ml Benzol versetzt« Das Gemistih wird unter Rttckflußs bis zur völligen Alkylierung (Auflösung) des 2-( ,K-Pyridyl)-benzimidazole erhitzt. Das benzolisohe Re.: \ tionsgemisch wird durch Filtrieren vom ausgeschiedenen anorganischen Salz (KOI) bzw. vom Überschuss der Base (kOH) befreit. Das Filtrat wird fraktioniert destilliert .19.52 g (0.1 mol) 2-Qi-pyridyl) benziraidazole and 11.2 g (0.2 hol) of freshly powdered potassium hydroxide are suspended in 200 ml of dry 3enzol and treated with a solution of 13.6 g (0.1 mol) N- (i '"- Chl6rEthyl) - diethylamine base in 50 ml of benzene added «Das Gemistih is heated under reflux until complete alkylation (dissolution) of 2- (, K-pyridyl) -benzimidazole. The benzeneohe reaction mixture is filtered by filtration freed from the precipitated inorganic salt (KOI) or from the excess of the base (kOH). The filtrate will fractionally distilled.

Di» l-$-Diäthylaminoäthyl)-2-(V -pyridyl)- -benzimidazol-Base siedet bei 0,8 Torr bei 240-2450O. Das aus der ätheriBch-alkoholisohen Lösung der Base gefällte Hydrochlorid schmilzt bei 225-2270CDi 'l - $ - diethylaminoethyl) -2- (V pyridyl) - benzimidazole base boils The precipitated from the ätheriBch-alkoholisohen solution of the base hydrochloride melts at 225-227 at 0.8 torr at 240-245 0 O. 0 C

In ähnlicher Weise werden, unter Verwendung von äquimolekularen Mengen der entsprechenden Ausgangsstoffe die in der nachstehenden Tabelle aufgezählten weiteren Verbindungen der allgemeinen Formel I hergestellt:Similarly, using equimolecular amounts of the appropriate starting materials the other compounds of general formula I listed in the table below are prepared:

009816/186^009816/186 ^

Kp* °C/ma (Base) Ausbeut· P. 0C (Dihydroohlorid) £Bp * ° C / ma (base) yield · P. 0 C (dihydrochloride) £

•ΟΟΗ,• ΟΟΗ,

H -NH -N

'O2H5 'O 2 H 5

H-NH-N

r-\r- \

-N-N

-H-H

Ν00Η3 Ν 00Η 3

H* -I 240-60/1,0-1,5 196-99 H * -I 240-60 / 1.0-1.5 196-99

220/2,5 230-32220 / 2.5 230-32

230/2,5 225-41/6/230 / 2.5 225-41 / 6 /

230/2,5 120-23230 / 2.5 120-23

232-34/0,2 198-200232-34 / 0.2 198-200

280/0,8 138-41280 / 0.8 138-41

260/0,8 Bi COpt63-64) 203-06260 / 0.8 Bi COpt63-64) 203-06

250-60/1,0 206-00250-60 / 1.0 206-00

0099100991

Kp. °O/mm (Base) AuebetiteKp. ° O / mm (Base) Auebetite F. 0O (Dihydroohlorid) gSF. 0 O (dihydrochloride) gS

Ü/2% O2H5 O / 2% O 2 H 5

-N-N

238/0,8 208-10238 / 0.8 208-10

240-45/0,8 225-27240-45 / 0.8 225-27

OoHOoH

2"5 220/Oi9 181-84 2 "5 220 / Oi9 181-84

JOJO

-H
\
-H
\

,P2H5 , P 2 H 5

C2H5 24O/l,O-l#5 193-97C 2 H 5 24O / l, Oil # 5 193-97

C2H5 C 2 H 5

V5 232/0,25 182-84 V 5 232 / 0.25 182-84

009816/1851 bad" original009816/1851 bad "original

Claims (2)

PATENTANSPRÜCHE 15/5780PATENT CLAIMS 15/5780 1. Verfahren zur Herstellung von neuen substituierten Benzimidazolderivaten der allgemeinen Formel I1. Process for the preparation of new substituted benzimidazole derivatives of the general formula I. G-R1 GR 1 - worin R^ für Wasserstoff oder für eine Phenyl·', Methoxyphenyl-j Trimethoxyphenyl-, Furyl·-, Pyridyl*» oder Aethylpyridylgruppe, R2 für eine Dime thy laaino-, Diäthylamino-, Morpaolino-, Piperidino- öder Pyrroii* dinogruppe stehen, wobei aber in Fällen, wenn R^ eine Phenyl- oder Methoxyphenylengruppe bedeutet, R„ keine Dirnethylamino— oder Piperidinogruppe sein kann* η = 2 oder 3, - dadurch gekennzeichnet, dass man Benzimidazole der allgemeinen Formel II- where R ^ for hydrogen or for a phenyl · ', methoxyphenyl-j trimethoxyphenyl, furyl · -, pyridyl * »or ethylpyridyl group, R 2 for a dimethylaaino, diethylamino, morphoolino, piperidino or pyrroii * dino group stand, but in cases when R ^ is a phenyl or methoxyphenylene group, R "cannot be a dimethylamino or piperidino group * η = 2 or 3, - characterized in that benzimidazoles of the general formula II IIII in an sich bekannter Weise mit Aminoalkylenhalogenide der allgemeinen Formel IIIin a manner known per se with aminoalkylene halides of the general formula III X - (CH2)n - R2 III X - (CH 2 ) n - R 2 III worin X für ein Halogenatom steht und R^, R2 und η die obige Bedeutung haben, kondensiert und gegebenenfalls die erhaltene Verbindung in ein therapeutischwherein X stands for a halogen atom and R ^, R 2 and η have the above meanings, condensed and optionally the compound obtained into a therapeutic BADORiGJNAL 009816/1851BADORiGJNAL 009816/1851 anwendbares Salz oder vorteilhaft in ein quatern£ree bBilz Überführt.applicable salt or advantageously converted into a quaternary mushroom . 2. Verfahren nach Anspruch 1, dadurch gekennzeichnet, dass man die hergestellte Base, bzw. deren Salz oder quaternäres Derivat an sich oder in Kombination mit weiteren therapeutisch wirksamen Verbindungen.» unter Anwendung von in der Pharmazie üblichen Hilfestoffen, zu gebrauchsfertigen A3?zneimit»t«lpaHipajÄteii verarbeitet.2. The method according to claim 1, characterized in that that the base produced, or its salt or quaternary derivative per se or in combination with other therapeutically active compounds. " using the aids customary in pharmacy to make ready-to-use A3? zneimit »t« lpaHipajÄteii processed. "" 8 " BAD"" 8 "BATHROOM 009816/1851009816/1851
DE19651545780 1965-11-29 1965-11-29 Process for the preparation of substituted benzimidazole derivatives Pending DE1545780A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DEE0030557 1965-11-29

Publications (1)

Publication Number Publication Date
DE1545780A1 true DE1545780A1 (en) 1970-04-16

Family

ID=7074581

Family Applications (1)

Application Number Title Priority Date Filing Date
DE19651545780 Pending DE1545780A1 (en) 1965-11-29 1965-11-29 Process for the preparation of substituted benzimidazole derivatives

Country Status (2)

Country Link
DE (1) DE1545780A1 (en)
GB (1) GB1060558A (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2300018A1 (en) * 1973-01-02 1974-07-04 Knoll Ag BASIC SUBSTITUTED BENZIMIDAZOLE COMPONENTS

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102206204B (en) * 2011-04-08 2012-12-12 奇方(天津)医药科技有限公司 Benzimidazole compound and medicinal application thereof

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2300018A1 (en) * 1973-01-02 1974-07-04 Knoll Ag BASIC SUBSTITUTED BENZIMIDAZOLE COMPONENTS

Also Published As

Publication number Publication date
GB1060558A (en) 1967-03-08

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