DE1923821A1 - Tetrahydrobenzodiazepinedione derivs with - valuable cns properties - Google Patents

Tetrahydrobenzodiazepinedione derivs with - valuable cns properties

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DE1923821A1
DE1923821A1 DE19691923821 DE1923821A DE1923821A1 DE 1923821 A1 DE1923821 A1 DE 1923821A1 DE 19691923821 DE19691923821 DE 19691923821 DE 1923821 A DE1923821 A DE 1923821A DE 1923821 A1 DE1923821 A1 DE 1923821A1
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benzo
diazepine
tetrahydro
dione
methyl
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German (de)
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Ehrhardt Dipl-Chem Dr Klaus
Schmidt Dipl-Chem Kurt
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WUELFING J A FA
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WUELFING J A FA
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
    • C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
    • C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
    • C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04C—ROTARY-PISTON, OR OSCILLATING-PISTON, POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; ROTARY-PISTON, OR OSCILLATING-PISTON, POSITIVE-DISPLACEMENT PUMPS
    • F04C2/00—Rotary-piston machines or pumps
    • F04C2/08—Rotary-piston machines or pumps of intermeshing-engagement type, i.e. with engagement of co-operating members similar to that of toothed gearing
    • F04C2/10—Rotary-piston machines or pumps of intermeshing-engagement type, i.e. with engagement of co-operating members similar to that of toothed gearing of internal-axis type with the outer member having more teeth or tooth-equivalents, e.g. rollers, than the inner member
    • F04C2/107—Rotary-piston machines or pumps of intermeshing-engagement type, i.e. with engagement of co-operating members similar to that of toothed gearing of internal-axis type with the outer member having more teeth or tooth-equivalents, e.g. rollers, than the inner member with helical teeth

Abstract

3H benzo-1,4-diazepine-2,5-dione derivs (I): (where R1 = H, Cl, methyl, or CF3; R2 = H or methyl, R3 and R4 denote H, alkyl, alkenyl, cycloalkyl, or phenylalkyl, opt. with alkyl or alkoxy substituents in the ring, or -NR3R4 represents are pyrrolidine, piperidine, morpholine or hexamethyleneimine ring, opt. with lower alkyl substituents), are synthesised from corresponding 3-hydroxyalkyl-p- toluenesulphonates and amines R3R4NH. Prefd. example is 3-dimethylaminomethyl-1,2,4,5- 3H -benzo-1,4-diazepin-2,5-dione. The new derivs and their non toxic salts have a pronounced effect on the central nervous system and blood pressure.

Description

" 1,2,4,5-Tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion-Derivate, Verfahren zu ihrer Herstellung und ihre Verwendung zur Herstellung von Arzneipräparaten In der modernen Therapie haben Benzo-1,4-diazepin-Derivate wegen ihrer zentralen, insbesondere psychotonischen Wirkung eine besondere Bedeutung. Aus der Reihe der 1,2,4,5-Tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion-Derivate sind jedoch nur wenige Verbindungen in der Literatur bekannt geworden; vgl. . Mijatake und S. Kaga, J0 PharmO SocO Japan, Band 72, Seite 1160 (1952); Cheuk-Man Lee, J. of Heterocyclic Chem., Volt 1 (1964), Seite 235 bis 238; Französisches Arzneimittelpatent 6621 M0 Nicht beschrieben sind in der Literatur bisher Verbindungen, die in 3-Stellung da Benzo-1,4-diazepin-2,5-dion-Ringes einen Substituenten mit einer funktionellen Gruppe tragen."1,2,4,5-Tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione derivatives, method for their manufacture and their use for the manufacture of medicinal products In of modern therapy have benzo-1,4-diazepine derivatives because of their central, in particular psychotonic effect has a special meaning. From the series of the 1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione derivatives however, only a few compounds have become known in the literature; see. . Mijatake and S. Kaga, J0 PharmO SocO Japan, vol. 72, p. 1160 (1952); Cheuk-Man Lee, J. of Heterocyclic Chem., Volt 1 (1964), pages 235-238; French drug patent 6621 M0 So far, the literature has not described compounds which are in the 3-position because benzo-1,4-diazepine-2,5-dione ring has a substituent with a functional group wear.

Die Erfindung betrifft neue 1,2,4,5-Tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion-Derivate der allgemeinen Formel I in der R1 ein Wasserstoff- oder Chloratom, eine Methyl- oder Trifluormethylgruppe, R2 ein Wasserstoffatom oder eine Methylgruppe und R3 und R4, die gleich oder verschieden sein können, Wasserstoffatome, unverzweigte oder verzweigte Alkyl- oder Alkenylreste mit 1 bis 6 C-Atomen, 5- bis 7-gliedrige Cycloalkylreste, die gegebenenfalls durch einen oder mehrere Alkylreste mit 1 bis 4 C-Atomen substituiert sind, oder Phenylalkylreste bedeuten, die im Phenylrest durch Alkyl- oder Alkoxyreste mit 1 bis 3 C-Atomen substituiert sind, und deren Alkylrest 1 bis 4 C-Atome enthält und unverzweigt oder verzweigt ist, oder R3 und R4 zusammen mit dem Stickstoffatom einem Pyrrolidino-, Piperidino-, Morpholino-oder Hexamethylen-iminorest bilden, der gegebenenfalls durch einen oder mehrere Alkylreste mit 1 bis 4 CXAbomen substituiert ist, und ihre Salze mit Säuren und quartären Ammoniumsalze.The invention relates to new 1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione derivatives of the general formula I. in which R1 is a hydrogen or chlorine atom, a methyl or trifluoromethyl group, R2 is a hydrogen atom or a methyl group and R3 and R4, which can be identical or different, hydrogen atoms, straight or branched alkyl or alkenyl radicals with 1 to 6 carbon atoms, 5- to 7-membered cycloalkyl radicals which are optionally substituted by one or more alkyl radicals having 1 to 4 carbon atoms, or phenylalkyl radicals which are substituted in the phenyl radical by alkyl or alkoxy radicals having 1 to 3 carbon atoms, and their alkyl radical Contains 1 to 4 carbon atoms and is unbranched or branched, or R3 and R4 together with the nitrogen atom form a pyrrolidino, piperidino, morpholino or hexamethylene-imino radical, which is optionally substituted by one or more alkyl radicals having 1 to 4 CX atoms , and their salts with acids and quaternary ammonium salts.

Die Verbindungen der Erfindung haben wertvolle Physiologische Eigenschaften. Sie zeigen unter anderem erhebliche zentrale Effekte und starke Blutdruckeffekte.The compounds of the invention have valuable physiological properties. Among other things, they show considerable central effects and strong blood pressure effects.

Die Er£wndung betrifft ferner ein Verfahren zur Herstellung der Verbindungen der allgemeinen Formal I, das dadurch gekennzeichnet ist, dass man den p-Toluolsulfonsäureester eines 3-Hdroxyalkyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dions der allgemeinen Formel II in der R1 und R2 die vorstehend angegebene Bedeutung haben, mit mindestens äquimolaren Mengen eines Amins der allgemeinen Formel III in der R3 und R4 die vorstehend angegebene Bedeutung haben, kondensiert und gegebenenfalls die erhaltene Base durch Umsetzung mit einer anorganischen oder organischen Säure in ihr Salz überführt oder gegebenenfalls durch Umsetzung mit einem Alkylierungs mittel in das quartäre Ammoniumsalz verwandelt.The invention also relates to a process for the preparation of the compounds of general formula I, which is characterized in that the p-toluenesulfonic acid ester of a 3-hydroxyalkyl-1,2,4,5-tetrahydro- [3H] -benzo-1 , 4-diazepine-2,5-dione of the general formula II in which R1 and R2 have the meaning given above, with at least equimolar amounts of an amine of the general formula III in which R3 and R4 have the meaning given above, condensed and optionally converted the base obtained into its salt by reaction with an inorganic or organic acid or optionally converted into the quaternary ammonium salt by reaction with an alkylating agent.

Die Ausgangsverbindungen der allgemeinen Formel II werden gemäss der deutschen Patentanmeldung W 45 562 IVd/12 p hergestellte beispiele für geeignete Amine der allgemeinen Formel III sind Methylamin, Äthylamin, n-Propylamin, Isopropylamin, Dimethylamin, Methyläthylamin, Diäthylamin, Di-n-propylamin, Methyl-n-propylamin, Methylisopropylamin, Äthylpropylamin, Äthylisopropylamin, Dibutylamin, Methylbutylamin, Äthylbutylamin, n-Propylbutylamin, Isobutylpropylamin, Pentylamin-(1), Pentylamin-(2), verzweigte Pentylamine, Hexylamin-(1), Hexylamin-(2), Hexylamin-(3), verzweigte Hexylamine, Cyclopentylamin, methylsubstituierte Cyclopentylamine, Cyclohexylamin, methylsubstituierte Cyclohexylamine, Cycloheptylamin, Allylamin, Methallylamin, Crotylamin, 5-Hexenylamin, Benzylamin, p-Tolylamin, o-Tolylamin, o,o'-Dimethylbenzylamin, p-Methoxybenzylamin, 3,4-Dimethoxybenzylamin, 3,4-Dimethylbenzylamin, 3,4,5-Trimethoxybenzylamin, ß-Phenyläthylamin, α-Phenyläthylamin, ß-Phenyl-α-äthylamin, γ-Phenylpropylamin, ß-Phenylpropylamin, Diphenylmethylamin, Pyrrolidin, Piperidin, Hexamethylenimin, Morpholin, 2,4-Dimethylpyrrolidin, 2,5-Dimethylpyrrolidin, 2-Butylpyrrolidin, 2-Methylpiperidin, 3-Methylpiperidin, 4-Methylpiperidin, 2,6-Dimethylpiperidin, 2,5-Dimethylpiperidin, 2,3-Dimethylpiperidin, 4,4,-Dimethylpiperidin, 2,2,4-Trimethylpiperidin, 2,3,6-Trimethylpiperidin, 2,2,6,6#Tetramethylpiperidin, 2-Äthylpiperidin, 3-Äthylpiperidin, 4-Äthylpiperidin, 4-Isopropylpiperidin, 4-Butylpiperidin und 2,6-Dimethylmorpholin.The starting compounds of the general formula II are according to the German patent application W 45 562 IVd / 12 p produced examples of suitable Amines of the general formula III are methylamine, ethylamine, n-propylamine, isopropylamine, Dimethylamine, methylethylamine, diethylamine, di-n-propylamine, methyl-n-propylamine, Methylisopropylamine, ethylpropylamine, ethylisopropylamine, dibutylamine, methylbutylamine, Ethylbutylamine, n-propylbutylamine, isobutylpropylamine, pentylamine- (1), pentylamine- (2), branched Pentylamine, hexylamine- (1), hexylamine- (2), hexylamine- (3), branched hexylamines, cyclopentylamine, methyl-substituted cyclopentylamines, cyclohexylamine, methyl-substituted cyclohexylamine, cycloheptylamine, allylamine, methallylamine, Crotylamine, 5-hexenylamine, benzylamine, p-tolylamine, o-tolylamine, o, o'-dimethylbenzylamine, p-methoxybenzylamine, 3,4-dimethoxybenzylamine, 3,4-dimethylbenzylamine, 3,4,5-trimethoxybenzylamine, ß-phenylethylamine, α-phenylethylamine, ß-phenyl-α-ethylamine, γ-phenylpropylamine, ß-phenylpropylamine, diphenylmethylamine, pyrrolidine, piperidine, hexamethyleneimine, Morpholine, 2,4-dimethylpyrrolidine, 2,5-dimethylpyrrolidine, 2-butylpyrrolidine, 2-methylpiperidine, 3-methylpiperidine, 4-methylpiperidine, 2,6-dimethylpiperidine, 2,5-dimethylpiperidine, 2,3-dimethylpiperidine, 4,4-dimethylpiperidine, 2,2,4-trimethylpiperidine, 2,3,6-trimethylpiperidine, 2,2,6,6 # tetramethylpiperidine, 2-ethylpiperidine, 3-ethylpiperidine, 4-ethylpiperidine, 4-isopropylpiperidine, 4-butylpiperidine and 2,6-dimethylmorpholine.

Amine, die bei der notwendigen Reaktionstemperatur gasförmig sind, setzt man in Gegenwart eines geeigneten Lösungsmittels im Autoklaven um. Nach Abdampfen des Aminüberschusses bzw. des Lösungsmittels wird der kristalline Rückstand umkristallisiert, bzw.Amines, which are gaseous at the necessary reaction temperature, is reacted in the presence of a suitable solvent in the autoclave. After evaporation the excess amine or the solvent, the crystalline residue is recrystallized, respectively.

durch Aufnehmen mit Säure, wie einer Halogenwasserstoffsäure, in das entsprechende Salz überführt und auskristallisiert. Als geeignete Lösungsmittel kommen für das Verfahren der Erfindung im wesentlichen die verfahrensgemäss eingesetzten Amine, ferner niedere Alkohole, wie Äthanol oder Butanol, in Frage. Zur Verbesserung der Löslichkeit der Ausgangsverbindung kann man gegebenenfalls ein tertiäres Amin, wie Triäthylamin, hinzugeben.by taking up with acid, such as a hydrohalic acid, into the appropriate salt transferred and crystallized. As a suitable solvent essentially those used according to the method come for the method of the invention Amines, and also lower alcohols such as ethanol or butanol, are possible. For improvement the solubility of the starting compound can optionally be a tertiary amine, like triethylamine, add.

Die Umsetzung des Amins mit der p p-Toluolsulfonsäureester wird im allgemeinen bei Temperaturen zwischen 50 und 200°C, vorzugsweise in Bereich von 100°C, oder bei der Rückflusstemperatur des eingesetzten Amins durchgeführt.The reaction of the amine with the p-toluenesulfonic acid ester is im generally at temperatures between 50 and 200 ° C, preferably in the range of 100 ° C, or carried out at the reflux temperature of the amine used.

Zur Herstellung der Salze mit Säuren werden die Basen entweder in wasserfreiem Alkohol gelöst und mit einer Alkohollösung einer an organischen oder organischen Säure oder durch Zugabe der Säure oder durch Einleiten von gasförmigem Halogenwasserstoff gefällt9 oder durch Eindampfen der alkoholischen Lösung auskristallisiert und .5m Anschluss daran umkristallisiert0 Zur Herstellung der quarz tären Ammoniumsalze werden vorzugsweise Alkylierungsmittel mit 1 bis 3 C-Atomen im Alkylrest verwendet, wie Methylbromid, Äthylchlorid und Propyljodid oder Dialkylsulfate, wie Dimethylsulfat.To prepare the salts with acids, the bases are either in Dissolved anhydrous alcohol and with an alcohol solution one of organic or organic acid or by adding the acid or by passing in gaseous acid Hydrogen halide precipitated9 or crystallized out by evaporation of the alcoholic solution and .5m afterwards recrystallized0 for the production of the quartz-tarry ammonium salts alkylating agents with 1 to 3 carbon atoms in the alkyl radical are preferably used, such as methyl bromide, ethyl chloride and propyl iodide or dialkyl sulfates such as dimethyl sulfate.

Die Beispiele erläutern die Erfindung. Die Herstellung der p-Toluolsulfonsäureester, die im Verfahren der Erfindung als Ausgangs; verbindungen verwendet werden können wird in den Beispielen 1 bis 5 erläutert.The examples illustrate the invention. The production of p-toluenesulfonic acid esters, in the method of the invention as the starting point; connections can be used is illustrated in Examples 1 to 5.

Beispiel 1 3-p-Tosyloxymethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion 10,3 g 3-Hydroxymethyl-benzo-1,4-diazepin-2,5-dion (F. 251° C) werden in 150 nil reinem Pyridin in der Hitze gelöst. Anschliessend wird die Lösung im Eisbad auf 0° a abgekühlt und mit 10 g p-Toluolsulfonylchlorid versetzt. Hat sich alles gelöste wird die KEhlung entfernt und das Gemisch solange stehen gelassen, bis es sich auf Raumtemperatur erwärmt hat. Dann wird das Gemisch innerhalb 30 Minuten in 3 Liter auf ca. 5 bis 10°C gekühltes Wasser eingerührt. Der dabei auftretende anfangs milchigtrübe Niederschlag ballt Sich Dach längerem Stehen zusammen und kann, nachdam er sich abgesetzt hat, in einer Nutsche gesammelt werden. Er wird zunächst mit wenig verdünnter Salzsäure und dann mit destilliertem Wasser ausgewaschen und auf einem Tonteller getrocknet. Ausbeute 15,7 g = 87 % der Theorie, F. 185 - 186° C.Example 1 3-p-Tosyloxymethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione 10.3 g of 3-hydroxymethyl-benzo-1,4-diazepine-2,5-dione (melting point 251 ° C.) are dissolved in 150 nil pure pyridine dissolved in the heat. The solution is then dissolved in an ice bath Cooled to 0 ° a and treated with 10 g of p-toluenesulfonyl chloride. Everything has been resolved the cooling is removed and the mixture is left to stand until it is on Has warmed up to room temperature. Then the mixture is poured into 3 liters within 30 minutes Stir in water cooled to approx. 5 to 10 ° C. The one that occurs initially milky precipitation clumps the roof after standing for a longer period of time and can, after he has settled, be collected in a suction filter. He will first Washed out with a little dilute hydrochloric acid and then with distilled water and dried on a clay plate. Yield 15.7 g = 87% of theory, mp 185-186 ° C.

Beispiel 2 3-(1'-Tosyloxyäthyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion Aus 1,09 g 3-(1'-Hydroxyäthyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepindion (F.246° C) gewinnt man in analoger Weise wie im Beispiel 1 0,9 g Produkt vom F. 205 - 206°C.Example 2 3- (1'-Tosyloxyethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione From 1.09 g of 3- (1'-hydroxyethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepinedione (mp. 246 ° C) 0.9 g of product with a melting point of 205-206 ° C. is obtained in a manner analogous to that in Example 1.

Beispiel 3 7-Methyl-3-tosyloxymethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-dizepin-2,5-dion Aus 11 g 7-Methyl-3-hydroxymethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion (Fo 260 - 262°C)gewinnt man das Prpdukt in analoger Weise wie im Beispiel 1 (18,5 g Produkt vom F. 199 -201°C.Example 3 7-Methyl-3-tosyloxymethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-dizepine-2,5-dione From 11 g of 7-methyl-3-hydroxymethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione (Fo 260 - 262 ° C) the product is obtained in a manner analogous to that in Example 1 (18.5 g of product with a melting point of 199-201 ° C.

Beispiel 4 7-Chlor-3-tosyloxymethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion Aus 2,4 g 7-Chlor-3-hydroxymethyl-1,2,4,5-tetrahydro-[3]-benzo-1,4-diazepin-2,5-dion (F. 2500 C) gewinnt man in analoger Weise wie in Beispiel 1 3,5 g Produkt vom F. 196 - 198°C.Example 4 7-Chloro-3-tosyloxymethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione From 2.4 g of 7-chloro-3-hydroxymethyl-1,2,4,5-tetrahydro- [3] -benzo-1,4-diazepine-2,5-dione (F. 2500 C) is obtained in a manner analogous to Example 1 3.5 g of product from F. 196-198 ° C.

Beispiel 5 7-Trifluormethyl-3-tosyloxymethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion Aus 7-Trifluormethyl-3-hydroxymethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion gewinnt man in analoger Weise wie im Beispiel 1 das Produkt in 80 % Ausbeute.Example 5 7-Trifluoromethyl-3-tosyloxymethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione From 7-trifluoromethyl-3-hydroxymethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione the product is obtained in a yield of 80% in a manner analogous to that in Example 1.

Beispiel 6 a) 3-Diäthylaminomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion 3,6 g Verbindung gemäss Beispiel 1 werden in einem 100 ml Rundkol ben mit aufgesetztem Kühler unter Rückfluss zwei Stunden in überschüssigem Diäthylamin gekocht. Das überschüssige Diäthylamin wird unter vermindertem Druck abdestilliert und der Rückstand in wenig Alkohol aufgenommen. Nach längerem Stehen erfolgt Kristallisation. Die kristalle werden abfiltriert und mit wenig Alkohol und Äther gewaschen und getrocknet. Die Ausbeute beträgt 810 mg (30 % der Theorie) vom F. 243 - 245°C.Example 6 a) 3-Diethylaminomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione 3.6 g of the compound according to Example 1 are placed in a 100 ml round-bottomed flask with a Condenser refluxed for two hours in excess diethylamine. The excess Diethylamine is distilled off under reduced pressure and the residue in a little Alcohol ingested. Crystallization occurs after standing for a long time. The crystals are filtered off, washed with a little alcohol and ether and dried. the Yield is 810 mg (30% of theory) with a melting point of 243 ° -245 ° C.

b) 3-Diäthylaminomethyl-1,2,4,5-tetrahydro-[3]-benzo-1,4-diazepin-2,5-dion-hydrochlorid 2,61 g Verbindung gemäss Beispiel 6 a werden in überschüssiger gesättigter alkoholischer HCl-Lösung gelöst. Die Lösung wird im Eisbad gekühlt. Nach kurzer Zeit setzt die Kristallisation ein.b) 3-Diethylaminomethyl-1,2,4,5-tetrahydro- [3] -benzo-1,4-diazepine-2,5-dione hydrochloride 2.61 g of the compound according to Example 6a are in excess saturated alcoholic HCl solution dissolved. The solution is cooled in an ice bath. After a short time, the Crystallization.

Das Hydrochlorid wird abfiltriert, mit wenig wasserfreiem Äther gewaschen und über CaCl2 im Vakuumexsikkator getrocknet. Ausbeute 2,7 g vom F. 164 - 166°C.The hydrochloride is filtered off and washed with a little anhydrous ether and dried over CaCl2 in a vacuum desiccator. Yield 2.7 g, mp 164-166 ° C.

Beispiel 7 a) 3-Pyrrolidinomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion 5,4 g Verbindung gemäss Beispiel 1 werden 2 Stunden unter leichteG Erwärmen in einem 100 ml Rundkolben mit aufgesetztem Kühler in überschüssigem Pyrrolidin gekocht. Dabei geht die eingesetzte werbindung vollstandig in Lösung. Das nicht umgesetzte Pyrrolidin wird unter vermindertem Druck abdestilliert und der Rückstand in wenig Alkohol aufgenommen. Dabei tritt vollständige Kristallisa tion ein, Die Kristalle werden abfiltriert, mit Alkohol und Äther gewaschen und auf einem Tonteller getrocknet. Ausbeute 1,7 g (45 % der Theorie) vom F. 185 - 186°C.Example 7 a) 3-Pyrrolidinomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione 5.4 g of the compound according to Example 1 are heated for 2 hours in a 100 ml round bottom flask with attached condenser boiled in excess pyrrolidine. The advertising connection used is completely dissolved. The not implemented Pyrrolidine is distilled off under reduced pressure and the residue in a little Alcohol ingested. Complete crystallization occurs, the crystals are filtered off, washed with alcohol and ether and dried on a clay plate. Yield 1.7 g (45% of theory) with a mp 185-186 ° C.

b) 3-Pyrrolidinomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diaze pin-2,5-dion-hydrochlorid Das gemäss Beispiel 6 b gewonnene Produkt schmilzt bei 243 245°C.b) 3-pyrrolidinomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diaze pin-2,5-dione hydrochloride The product obtained according to Example 6b melts at 243 245 ° C.

Beispiel 8 a) 3-Piperidinomethyl-1,2,4,5-tetrahydro-[3]-benzo-1,4-diazepin-2,5-dion Aus 3,6 g Verbindung gemäss Beispiel 1 erhält man gemäss Beispiel 7 a durch Umsetzung mit Piperidin 25 g Produkt vom F. 210°C.Example 8 a) 3-Piperidinomethyl-1,2,4,5-tetrahydro- [3] -benzo-1,4-diazepine-2,5-dione From 3.6 g of the compound according to Example 1, according to Example 7 a is obtained by reaction with piperidine 25 g of product with a mp of 210 ° C.

2-Piperidinomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion-hydrochlorid Das gemäss Beispiel 6 b gewonnene Produkt schmilzt bei 219 -221°C.2-piperidinomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione hydrochloride The product obtained according to Example 6b melts at 219-221 ° C.

Beispiel 9 a) 3-Morpholinomethyl-1,2,4,5-terahydro-[3H]-benzo-1,4-diazepin-2.5-dion Aus 3,6 g Verbindung gemäss Beispiel 1 erhält man gemäss Beispiel 7 a durch Umsetzung mir Morpholin 2,2 Produkt vom F. 233 -235° C.Example 9 a) 3-Morpholinomethyl-1,2,4,5-terahydro- [3H] -benzo-1,4-diazepine-2,5-dione From 3.6 g of the compound according to Example 1, according to Example 7 a is obtained by reaction with morpholine 2.2 product with a temperature of 233-235 ° C.

b) 3-Morpholinomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion-hydrochlorid Das gemäss Beispiel 6 b gewonnene Produkt schmilzt bei 240 -242° C.b) 3-morpholinomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione hydrochloride The product obtained according to Example 6b melts at 240-242 ° C.

Beispiel 10 a) 3-Benzylaminomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion 1S8 g Verbindung gemäss Beispiel 1 werden in einem 50 ml Rundkolben mit aufgesetztem Kühler (ohne Kühlwasser) in überschüssigem Benzylamin im ölbad auf 1100 C erhitzt. Nach 2 Stunden hat sich alles aufgelöst. Danach wird restliches Benzylamin unter vermindertem Druck abdestilliert. Der kristalline Rückstand wird in wenig Alkohol digeriert und abfiltriert. Die Kristalle werden mit Äther gewaschene Ausbeute 1,3 g Produkt vom ?. 203 - 205°C.Example 10 a) 3-Benzylaminomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione 158 g of the compound according to Example 1 are placed in a 50 ml round bottom flask with a Heated cooler (without cooling water) in excess benzylamine in an oil bath to 1100 C. After 2 hours everything dissolved. Thereafter, remaining benzylamine is under distilled off under reduced pressure. The crystalline residue is dissolved in a little alcohol digested and filtered off. The crystals are washed with ether yield 1.3 g product from?. 203-205 ° C.

b) 3-Benzylaminomethyl-1#2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion-hydrochlorid Das gemäss Beispiel 6 b gewonnene Produkt schmilzt bei 219 -221°C.b) 3-Benzylaminomethyl-1 # 2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione hydrochloride The product obtained according to Example 6b melts at 219-221 ° C.

Beispiel 11 a) 3-Phenyläthylaminomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion 3,6 g Verbindung gemäss Beispiel 1 werden mit Phenyläthylamin gemäss Beispiel 10 a umgesetzt. Man erhält 2,0 g Produkt vom F.Example 11 a) 3-Phenylethylaminomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione 3.6 g of the compound according to Example 1 are mixed with phenylethylamine according to Example 10 a implemented. 2.0 g of product from F.

186 - 188°C.186-188 ° C.

b) 3-Phenyläthylaminomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion-hydrochlorid Das gemäss Beispiel 6 b gewonnene Produkt schmilzt bei 176 -178°C.b) 3-Phenylethylaminomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione hydrochloride The product obtained according to Example 6b melts at 176-178 ° C.

Beispiel 12 a) 7-Methyl-3-diäthylaminomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion Aus 3,74 g Verbindung gemäss Beispiel 3 erhält man gemäss Beispiel 6 a durch Umsetzung mit Diäthylamin 2,0 g Produkt vom Schmelzpunkt 214 - 216°C.Example 12 a) 7-Methyl-3-diethylaminomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione From 3.74 g of the compound according to Example 3, according to Example 6 a is obtained by reaction with diethylamine 2.0 g of product with a melting point of 214-216 ° C.

b) 7-Methyl-3-diäthylaminomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion-hydrochlorid Das gemäss Beispiel 6 b gewonnene produkt schmilzt bei 225 -227° C.b) 7-methyl-3-diethylaminomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione hydrochloride The product obtained according to Example 6b melts at 225-227 ° C.

Beispiel 13 a) 7-Methyl-3-pyrrolidinomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion Aus 3,74 g Verbindung gemäss Beispiel 3 erhält man gemäss Beispiel 6 a durch Umsetzung mit Pyrrolidin 21 g Produkt vom Schmelzpunkt 181 - 183° Co 7-Methyl-3-pyrrolidinomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion-hydrochlorid Das gemäss Beispiel 6 a gewonnene Produkt schmilzt bei 227 -229°C.Example 13 a) 7-Methyl-3-pyrrolidinomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione From 3.74 g of the compound according to Example 3, according to Example 6 a is obtained by reaction with pyrrolidine 21 g of product with a melting point of 181-183 ° Co 7-methyl-3-pyrrolidinomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione hydrochloride The product obtained according to Example 6a melts at 227-229 ° C.

Beispiel 14 a) 7-Methyl-3-piperidinomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion Aus 9,35 der Verbindung gemäss Beispiel 3 erhält man gemäss Bespiel 6a durch, Umsetzung mit Piperidin 6 g Produkt vom Schmelzpunkt 213 - 215°C.Example 14 a) 7-Methyl-3-piperidinomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione From 9.35 of the compound according to Example 3, according to Example 6a, reaction is obtained with piperidine 6 g of product with a melting point of 213-215 ° C.

b) 7-Methyl-3-piperidinomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion-hydrochlorid Das gemäss Beispiel 6 a gewonnene Produkt schmilzt bei 206 -208° C.b) 7-methyl-3-piperidinomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione hydrochloride The product obtained according to Example 6a melts at 206-208 ° C.

Beispiel 15 a) 7-Methyl-3-morpholinomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion Aus 3,74 g Verbindung gemäss Beispiel 3 erhält man gemäss Beispiel 6 mit Morpholin 1,9 g Produkt vom Schmelzpunkt 193 -195° C.Example 15 a) 7-Methyl-3-morpholinomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione From 3.74 g of the compound according to Example 3, according to Example 6 with morpholine is obtained 1.9 g of product with a melting point of 193-195 ° C.

b) 7-Methyl-3-morpholinomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion-hydrochlorid Das gemass Beispiel 6 ob gewonnene Produkt schmilzt bei 187 189°C.b) 7-methyl-3-morpholinomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione hydrochloride The product obtained according to Example 6 ob melts at 187 189 ° C.

Beispiel 16 a) 7-Methyl-3-benzylaminomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion 3,09 g Verbindung gemäss Beispiel 3 werden in einem Überschuss von Benzylamin in einem 100 ml Rundkolben im Verlaufe von 2 Std. bei einer Öltemperatur von 120° C gelöst. Anschliessend wird überschüssiges Benzylamin unter vermindertem Druck abdestilliert. Als Rückstand hinterbleibt das kristalline Produkt. Es wird abfiltriert. Das Filtrat wird unter vermindertem Druck eingeengt. Restliches Benzylamin wird auf dem Wasserbad entfernt.Example 16 a) 7-Methyl-3-benzylaminomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione 3.09 g of the compound according to Example 3 are in an excess of benzylamine in a 100 ml round bottom flask in the course of 2 hours at an oil temperature of 120 ° C solved. Excess benzylamine is then distilled off under reduced pressure. The crystalline product remains as a residue. It is filtered off. The filtrate is concentrated under reduced pressure. Remaining benzylamine is on the water bath removed.

Aus dem Rückstand kann noch ein weiterer kleiner Anteil dea Producktesisoliert werden. Der Rückstand im Filter wird mit wenig Alkohol und Äther gewaschen. D:le Substanz ist kristallin und rein weiss. Ausbeute 1,1 g Produkt vom F. 215 - 217°C.A further small portion of the product can be isolated from the residue will. The residue in the filter is washed with a little alcohol and ether. D: le Substance is crystalline and pure white. Yield 1.1 g of product with a melting point of 215-217 ° C.

b) 7-Methyl-3-phenyläthylaminomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion-hydrochlorid 3,2 g Verbindung werden mit gesättigter alkoholischer HCl - Lösung versetzt. Das Hydrochlorid kristallisiert nach einiger Zeit in der Lösung aus. Ausbeute 3 g vom F. 170 - 172° C.b) 7-methyl-3-phenylethylaminomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione hydrochloride 3.2 g of the compound are mixed with saturated alcoholic HCl solution. That After some time, the hydrochloride crystallizes out in the solution. Yield 3 g of 170 - 172 ° C.

Beispiel 18 a) 7-Chlor-3-pyrrolidinomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion Aus 2,4 g Produkt gemäss Beispiel 4 erhält man mit überschüssigem Pyrrolidin gemäss Beispiel 6 a 1,2 g Produkt vom F. 164 - 166° C.Example 18 a) 7-Chloro-3-pyrrolidinomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione From 2.4 g of product according to Example 4, with excess pyrrolidine according to Example 6 a 1.2 g of product with a melting point of 164 - 166 ° C.

b) 7-Chlor-3-pyrrolidinomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion hydrochlorid Das gemäss Beispiel 6 b gewonnens Produkt schmilzt bei 189 - 1910 Co Beispiel 19 a) 7-Chlor-3-piperidinomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion Aus 2D4 g Produkt gemäss Beispiel 4 erhält man mit überschüssigem Piperidin gemäss Beispiel 6 a 1,3 g Produkt vom F. 191 - 193° C.b) 7-chloro-3-pyrrolidinomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione hydrochloride The product obtained according to Example 6b melts at 189 - 1910 Co Example 19 a) 7-Chloro-3-piperidinomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione From 2D4 g of product according to Example 4 is obtained with excess piperidine according to Example 6 a 1.3 g of product with a melting point of 191 ° -193 ° C.

b) 7-Chlor-3-piperidinomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion-hydrochlorid Das gemäss Beispiel 6 b gewonnene Produkt schmilzt bei 184 -186° C.b) 7-chloro-3-piperidinomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione hydrochloride The product obtained according to Example 6b melts at 184-186 ° C.

Die sn den Beispielen 20 bis 26 genannten Verbindungen werden in analoger Weise hergestellt.The compounds mentioned in Examples 20 to 26 are analogous Way made.

Beispiel 20 7-Methyl-3-cyclohexylaminomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion, F. 179-- 181° C; Hydrochlorid, F. 191 - 193°C.Example 20 7-Methyl-3-cyclohexylaminomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione, Mp 179-181 ° C; Hydrochloride, m.p. 191-193 ° C.

Benzoat, F. 157 - 159° C.Benzoate, m.p. 157-159 ° C.

Beispiel 21 7-Chlor-3-cyclohexylaminomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion, F. 184 - 186° C; Hydrochlorid, F. 216 - 218°C.Example 21 7-Chloro-3-cyclohexylaminomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione, M.p. 184-186 ° C; Hydrochloride, m.p. 216-218 ° C.

Beispiel 22 7-Chlor-3-benzylaminomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion, F. 189 - 191° C; Hydrochlorid, F. 226 - 228° C.Example 22 7-Chloro-3-benzylaminomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione, 189-191 ° C; Hydrochloride, m.p. 226 - 228 ° C.

Beispiel 23 3-Cyclohexylaminomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion, F. 189 - 191° C.Example 23 3-Cyclohexylaminomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione, 189 - 191 ° C.

Hydrochlorid, F. 211 - 213° C, Beispiel 24 3-Propylaminomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1.4-diazepin-2,5-dion, F. 171 - 173°C; Hydrochlorid, F. 206 - 208° C.Hydrochloride, mp 211-213 ° C, Example 24 3-propylaminomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione, Mp 171-173 ° C; Hydrochloride, m.p. 206 - 208 ° C.

Beispiel 25 7-Methyl-3-propylaminomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion, F. 183 - 185° C.Example 25 7-Methyl-3-propylaminomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione, F. 183 - 185 ° C.

Hydrochlorid, F. 203 - 205° C.Hydrochloride, m.p. 203-205 ° C.

Beispiel 26 3-(N-Methyl-Phenyläthylaminomethyl)-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion, F. 154 - 156° C.Example 26 3- (N-methyl-phenylethylaminomethyl) -1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione, 154-156 ° C.

Claims (1)

P a t e n t a n s p r ü c h e P a t e n t a n s p r ü c h e 1. 1,2,4,5-Tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion-Derivate der aigemeinen Formel X in der R1 ein Wasserstoff- oder Chloratom, eine Methyl- oder Trifluormethylgruppe, R2 ein Wasserstoffatom oder eine Methylgruppe und R3 und R4, die gleich oder verschieden sein können, Wasserstoffatome, unverzweigte oder verzweigte Alkyl- oder Alkenylreste mit 1 bis 6 C-Atomen, 5- bis 7-gliedrige Cycloalkylreste, die gegebenenfalls durch einen oder mehrere Alkylreste mit 1 bis 4 C-Atomen substituert sind, oder Phenylalkylreste bedeuten, die im Phenylrest durch Alkyl- oder Alkoxyreste mit 1 bis 3 C-Atomen substituiert sind, und deren Alkylrest 1 bis 4 C-Atome enthält und unverzweigt oder verzweigt ist, oder R3 und R4 zusammen mit dem Stickstoffatom einen Pyrrolidino, Piperidino-, Morpholino-oder Hexamethyleniminorest bilden, der gegebenenfalls durch einen oder mehrere Alkylreste mit 1 bis 4 C-Atomen substituiert ist, und ihre Salze mit Säuren und quartären Ammoniumsalze.1. 1,2,4,5-Tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione derivatives of the general formula X. in which R1 is a hydrogen or chlorine atom, a methyl or trifluoromethyl group, R2 is a hydrogen atom or a methyl group and R3 and R4, which can be identical or different, hydrogen atoms, straight or branched alkyl or alkenyl radicals with 1 to 6 carbon atoms, 5- to 7-membered cycloalkyl radicals which are optionally substituted by one or more alkyl radicals having 1 to 4 carbon atoms, or phenylalkyl radicals which are substituted in the phenyl radical by alkyl or alkoxy radicals having 1 to 3 carbon atoms, and their alkyl radical Contains 1 to 4 carbon atoms and is unbranched or branched, or R3 and R4 together with the nitrogen atom form a pyrrolidino, piperidino, morpholino or hexamethyleneimino radical, which is optionally substituted by one or more alkyl radicals with 1 to 4 carbon atoms, and their salts with acids and quaternary ammonium salts. 2. 3-Diäthylaminomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion.2. 3-Diethylaminomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione. 3. 3-Diäthylaminomethyl-1 2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2 5-di n @@@ schlarie 4. 3-Pyrrolidinomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion.3. 3-Diethylaminomethyl-1 2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2 5-di n @@@ schlarie 4. 3-Pyrrolidinomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione. 5. 3-Pyrrolidinomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion-hydrochlorid.5. 3-pyrrolidinomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione hydrochloride. 6. 3-Piperidinomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion.6. 3-piperidinomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione. 7. 3-Piperidinomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion-hydrochlorid.7. 3-piperidinomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione hydrochloride. 8. 3-Morpholinomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion.8. 3-Morpholinomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione. 9. 3-Morpholinomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion-hydrochlorid.9. 3-Morpholinomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione hydrochloride. 10. 3-Benzylaminomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion.10. 3-Benzylaminomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione. 11. 3-Benzylaminomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion-hydrochlorid.11. 3-Benzylaminomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione hydrochloride. 12. 3-Phenyläthylaminomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion.12. 3-Phenylethylaminomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione. 13. 3-Phenyläthylaminomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion-hydrochlorid.13. 3-Phenylethylaminomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione hydrochloride. 14. 7-Methyl-@-diäthylaminomethyl-1,2,4,5-tetrahydro-[3H]-benzo 1,4-diazepin @@-dion.14. 7-Methyl - @ - diethylaminomethyl-1,2,4,5-tetrahydro- [3H] -benzo 1,4-diazepine @@ - dion. 15. 7-Methyl-3-diäthylaminomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion-hydrochlorid.15. 7-Methyl-3-diethylaminomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione hydrochloride. 16. 7-Methyl-3-pyrrolidinomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion.16. 7-Methyl-3-pyrrolidinomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione. 17. 7-Methyl-3-pyrrolidinomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion-hydrochlorid.17. 7-Methyl-3-pyrrolidinomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione hydrochloride. 18. 7-Methyl-3-piperidinomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion.18. 7-Methyl-3-piperidinomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione. 19. 7-Methyl-3-piperidinomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion-hydrochlorid.19. 7-Methyl-3-piperidinomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione hydrochloride. 20. 7-Methyl3-morpholinomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion.20. 7-Methyl-3-morpholinomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione. 21. 7-Methyl-3-morpholinomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion-hydrochlorid.21. 7-Methyl-3-morpholinomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione hydrochloride. 22. 7-Methyl-3-benzylaminomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion.22. 7-Methyl-3-benzylaminomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione. 23. 7-Methyl-3-phenyläthylaminomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion-hydrochlorid.23. 7-Methyl-3-phenylethylaminomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione hydrochloride. 24. 7-Chlor-3-pyrrolidinomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion.24. 7-Chloro-3-pyrrolidinomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione. 25. 7-Chlor-3-pyrrolidinomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion-hydrochlorid.25. 7-Chloro-3-pyrrolidinomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione hydrochloride. 26. 7-Chlor-3-piperidinomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion.26. 7-Chloro-3-piperidinomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione. 27. 7-Chlor-3-piperidinomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion-hydrochlorid.27. 7-Chloro-3-piperidinomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione hydrochloride. 28. 7-Methyl-3-cyclohexylaminomethyl-1,2,4,5-tetra-hydro-[3H]-benzo-1,4-diazepin-2,5-dion.28. 7-Methyl-3-cyclohexylaminomethyl-1,2,4,5-tetra-hydro- [3H] -benzo-1,4-diazepine-2,5-dione. 19. 7-Methyl-3-cyclohexylaminomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion-hydrochlorid, 30. 7-Methyl-3-cyclohexylaminomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion-benzoat.19. 7-Methyl-3-cyclohexylaminomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione hydrochloride, 30. 7-Methyl-3-cyclohexylaminomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione-benzoate. 31. 7-Chlor-3-cyclohexylaminomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion.31. 7-Chloro-3-cyclohexylaminomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione. 32. 7-Chlor-3-cyclohexylaminomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion-hydrochlorid.32. 7-Chloro-3-cyclohexylaminomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione hydrochloride. 33. 7-Chlor-3-benzylaminomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion.33. 7-Chloro-3-benzylaminomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione. 34. 7-Chlor-3-benzylaminomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion-hydrochlorid.34. 7-Chloro-3-benzylaminomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione hydrochloride. 35. 3-Cyclohexylaminomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion.35. 3-Cyclohexylaminomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione. 36. 3-Cyclohexylaminomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion-hydrochlorid.36. 3-Cyclohexylaminomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione hydrochloride. 37. 3-Propylaminomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion.37. 3-Propylaminomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione. 38. 3-Propylaminomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion-hydrochlorid.38. 3-Propylaminomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione hydrochloride. 39. 7-Methyl-3-propylaminomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion.39. 7-methyl-3-propylaminomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione. 40. 7-Methyl-3-propylaminomethyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion-hydrochlorid.40. 7-methyl-3-propylaminomethyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione hydrochloride. 41. 3-(N-Methyl-Phenyläthylaminomethyl)-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dion.41. 3- (N-methyl-phenylethylaminomethyl) -1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5-dione. 42. Quartäre Ammoniumsalze der Verbindungen nach Anspruch 1 bis 4@, die sich von Alkylhalogeniden mit 1 bis 3 C-Atomen im Alkylrest ableiten.42. Quaternary ammonium salts of the compounds according to claim 1 to 4 @, which are derived from alkyl halides with 1 to 3 carbon atoms in the alkyl radical. 430- Verfahren zur Herstellung der Verbindungen nach Anspruch 1, d a d u r c h g e k e n n z e i c h n e t, dass man den p-Toluolsulfonsäureester eines 3-Hydroxyalkyl-1,2,4,5-tetrahydro-[3H]-benzo-1,4-diazepin-2,5-dions der allgemeinen Formel II in der R1 und R2 die in Anspruch 1 angegebene Bedeutung haben, mit mindestens äquimolaren Mengen eines Amins der allgemeinen Formel III im der R3 und R4 die in Anspruch 1 angegebene Bedeutung haben, kondensiert, und gegebenenfalls die erhaltene Base durch Umsetzung mit einer anorganischen oder organischen Säure in ihr Salz überführt oder gegebebefalls durch Umsetzung mit einem Alkylierungsmittel in das quartäre Ammoniumsalz verwandelt.430- Process for the preparation of the compounds according to claim 1, characterized by the fact that the p-toluenesulfonic acid ester of a 3-hydroxyalkyl-1,2,4,5-tetrahydro- [3H] -benzo-1,4-diazepine-2,5 -dions of the general formula II in which R1 and R2 have the meaning given in claim 1, with at least equimolar amounts of an amine of the general formula III in which R3 and R4 have the meaning given in claim 1, condensed, and optionally the base obtained is converted into its salt by reaction with an inorganic or organic acid or, if necessary, converted into the quaternary ammonium salt by reaction with an alkylating agent. 44. Verwendung der Verbindungen gemäss Anspruch 1 bis 42 zur Herstellung von Arzneipräparaten.44. Use of the compounds according to claims 1 to 42 for the preparation of medicinal products.
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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0167919A2 (en) * 1984-06-26 1986-01-15 Merck & Co. Inc. Benzodiazepine derivatives and pharmaceutical compositions containing them
US4576750A (en) * 1985-04-22 1986-03-18 Merck & Co., Inc. Tryptophan derivative
US4820834A (en) * 1984-06-26 1989-04-11 Merck & Co., Inc. Benzodiazepine analogs
EP0796252A1 (en) * 1994-12-09 1997-09-24 Smithkline Beecham Corporation Bicyclic fibrinogen antagonists
EP0892797A1 (en) * 1996-02-26 1999-01-27 Bristol-Myers Squibb Company Inhibitors of farnesyl protein transferase
DE19802025C1 (en) * 1998-01-21 1999-06-10 Werner Dipl Ing Arnswald Grinding pump for pumping waste water contg. solid material

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0167919A2 (en) * 1984-06-26 1986-01-15 Merck & Co. Inc. Benzodiazepine derivatives and pharmaceutical compositions containing them
US4820834A (en) * 1984-06-26 1989-04-11 Merck & Co., Inc. Benzodiazepine analogs
EP0167919B1 (en) * 1984-06-26 1993-05-05 Merck & Co. Inc. Benzodiazepine derivatives and pharmaceutical compositions containing them
US4576750A (en) * 1985-04-22 1986-03-18 Merck & Co., Inc. Tryptophan derivative
EP0796252A1 (en) * 1994-12-09 1997-09-24 Smithkline Beecham Corporation Bicyclic fibrinogen antagonists
EP0796252A4 (en) * 1994-12-09 1998-02-04 Smithkline Beecham Corp Bicyclic fibrinogen antagonists
EP0892797A1 (en) * 1996-02-26 1999-01-27 Bristol-Myers Squibb Company Inhibitors of farnesyl protein transferase
EP0892797A4 (en) * 1996-02-26 2004-10-20 Bristol Myers Squibb Co Inhibitors of farnesyl protein transferase
EP1481975A1 (en) * 1996-02-26 2004-12-01 Bristol-Myers Squibb Company Inhibitors of farnesyl protein transferase
DE19802025C1 (en) * 1998-01-21 1999-06-10 Werner Dipl Ing Arnswald Grinding pump for pumping waste water contg. solid material

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