SE188253C1 - - Google Patents

Description

Inventors: J U Biel The present invention relates to hydrazine derivatives and more particularly to a process for the preparation of aralkylaminoalkylhydrazines and the use of these compounds as psychotherapeutic agents. The invention also relates to the preparation of novel pharmaceutical preparations which contain an aralkylaminoalkylhydrazine.

According to the present invention, aralkylaminoalkylhydrazines of the formula R 1 R 5 R 2 have been found to be active monoamine oxidase inhibitors and active stimulants of the central nervous system and to be useful for the psychotherapeutic treatment of mental depression. In the above formula, Ar represents an aryl group, such as a phenyl group, a substituted phenyl group, for example, methylphenyl, chlorophenyl or methoxyphenyl, pyridyl, imidazolyl, thienyl or furyl, R represents hydrogen, an alkyl group and especially a lower alkyl group, e.g. . methyl, ethyl, propyl, butyl and the like, an alkylene group, e.g. an allyl group or a 1 (2-butenyl) group, an aralkyl group and especially phenyl-lower alkyl groups, shorn a benzyl group and a phenethyl group, an aryl group and especially a phenyl group, a cycloalkyl group and especially a cyclopentyl or cycloheptyl group, and heterocyclic alkyl groups, such as a 3-pyridylmethyl, tenyl, 2-furfurylmethyl, 2-furylmethyl or 2-imidazolylmethyl group, R 1 represents hydrogen or a lower alkyl group, such as a methyl, ethyl, propyl or isopropyl group, and in R 1 and R 2 are the same or different and represent vate, alkyl groups, especially lower alkyl groups, e.g. methyl, ethyl, propyl, butyl, pentyl and hexyl, acyl groups, e.g. acetyl, propionyl, butyryl, benzoyl and phenylacetyl, hydroxyalkyl groups, for example, hydroxymethyl, 3 seconds amino group, such as morpholino, pyrralidino, piperidino, 1,2,3,4-tetrahydroisoquinolino, 1,2,3,4-tetrahydroquinolino, isoindolino, 4 ethyl-1-, piperazino, hydroxypiperidino, indolino, theophylline, phenothiazino, straight or branched alkylene. group having the highest carbon atoms, B having a straight or branched lower alkylene group, Ro having a lower or lower alkyl group and. the group —B — CH— probably does not contain more than carbon atoms.

The invention is jok limited to nAgou, special theoretical explanation for the action of the new compounds but it is likely that these compounds pass through the blood barrier in the brain due to their monoamine oxidase inhibitory action and delay or prevent the metabolic enhancement of neurohumoropyrinins, . Serotonin and norepinephrine are present in the brain and probably serve as chemical transmitters in or stimulants for the central nervous system. A lack of available serotonin or norepinephrine in the brain, which may be caused, for example, by metabolism or degradation of these agents by monoamine oxidase, may result in the parasympathetic predominance which occurs with mental 2-hydromethyl and 3-hydroxypropyl, alkenyl groups and especially lower alkenyl groups. ex. ally1 and 1- (2-butenyl), aryl groups and especially a phenyl group, incl. phenyl groups substituted in the karnan, e.g. hydroxyphenyl, methoxyphenyl, chlorophenyl, acetoxyphenyl and the like, aralkyl groups and especially phenyl-lower alkyl groups, such as benzyl, phenethyl, phenylpropyl and lordenenylpropyl, cycloalkyl groups, such as cyclopentyl and Old °, hexyl, alkynyl groups, butylpropyl , and groups in which —N \ constitutes an eyclic `R.

Dupl. at 12 p: 2 2— - state of depression. By preventing or preventing enlargement of serotonin and norepinephrine by using the hydrazines of the invention, the content of Adana neurohumoral agents in the body can be increased for a longer period of time, so that sympathetic properties such as increased alertness and mobility are obtained. These hydrazines also stimulate the heart muscle and are therefore useful in treating people who are in a state of shock. The compounds also form salts with penicillin and can therefore be used to isolate this antibiotic. These compounds are suitably used for the above-mentioned spirals in the form of a joke toxic acid addition salt, such as the hydrochloride, hydrobromide, fumarate or sulphate.

Some of the new aralkylaminoalkylhydrazines can be conveniently prepared by reacting an aralkylaminoalkyl halogen with hydrazine or a monosubstituted hydrazine. This procedure can be ash-damaged by the following reaction formula: Ar-Y-N-B-CH-X R1 R Ar-Y-N-B-CH-N-NH, II R, R, R, van i Ar, R Y, B and R have the meanings given above and X represents a reaction-prone halogen, such as bromine, chlorine or iodine.

Some of the aralkylaminoalkyl halides which may be used in this process are N-benzyl-N-methylaminoethyl chloride, N-benzyl-Nallylaminoisopropyl bromide, N-2-pyridylmethylN-methylaminoethyl chloride, N-3-pyridylmethylaminoethyl-N-methyl-methyl-methyl , N-4-pyridylmethyl-N-methylaminoethyl chloride, N-2-tenyl-N-isopropylaminosec.-butyl chloride, N-2-furfurylmethyl-N-methylaminoisopropyl bromide, N-2-imidazolylmethyl-Nsec.-butylaminoethyl -Idoride, phenylpropylaminoethyl chloride and N-phenethyl-N-methylaminomethyl chloride.

In addition to hydrazine hydrate, monosubstituted hydrazines such as methylhydrazine, ethylhydrazine, isopropylhydrazine and butylhydrazine can be used.

The reaction is carried out by adding the aralkylaminoalkyl halide to a solution of a large excess, e.g. about 200%, of the hydrazine component of a solvent, such as methanol, ethanol, butanol or dioxane. Elevated temperature, for example up to reflux temperature, is usually used to increase the reaction rate. The desired reaction product can be isolated by distilling off the solvent, extracting the residue Hied a solvent, such as ether, and fractional distillation of the extract.

Some aralkylaminoalkylhydrazines which can be prepared in this way are N-benzyl-N-methylaminoethyl-hydrazine, N-chlorobenzyl-N-methylaminoisopropyl-hydrazine, N- (1-phenyl-2-propyl) -aminoethyl-hydrazine, N- (1-phenyl-2-propyl) -amino-isopropyl-hydrazine, N-phenethylaminoisopropyl-hydrazine, N-benzylaminoethyl-hydrazine, N-2-tenyl-Nisopropyl-sec-butyl-hydrazine and N-2-furfurylmethyl-N -methylaminoisopropyl-hydrazine.

The compounds in which R 5 and R 5 had other substituents in water, as well as those compounds in which R 4 or R 5 are hydrogen, can be conveniently prepared by reacting an aralkylaminoalkyl ketone or aldehyde with hydrazine or a substituted hydrazine, aralkylaminoalkylidenyl hydrazine or hydrazone as an intermediate, which is then reduced to the corresponding hydrazine. This process can be ash-damaged by the following reaction formulas: / RS Ar-Y - N --- B --- C = 0+ I \ Rs R, R, R3 Ar-Y — N — B — C = N — N / \ Rs R, Rs R, Ar-Y-N-B-CH-NH-N / "B4 R, R, van in Ar, Y, R 1, R 5 and R 4 have the meaning given, B represents a lower alkylene group and R vate or a lower alkyl group.

As representative examples of aralkylaminoalkyl ketones and aldehydes which may be used in this process, there may be mentioned N-benzyl-N-methylamino-acetaldehyde, 2- (N-chlorobenzyl-N-ethylamino) -propionaldehyde, α- (N-3-pyrridylmethyl -N-methylamino) -2-propanone, α- (N-4-pyridylmethyl-N-methylamino) -2-butanone, 2-thienylmethylamino-propionaldehyde, N-phenethyl-N-ethylaminopropyl-methyl-ketone, and 2-furylmethylaminoacetaldehyde .

As representative examples of the hydrazines which can be used in the process, nananase hydrazine, actylhydrazines, sisom acetylhydrazine, propionylhydrazine, benzoylhydrazine, phenylacetylhydrazine, isonicotinylhydrazine, monosubstituted hydrazylethrazine, phenylethrazine, sisrazine, hydrazines, such as N, N-dimethylhydrazine, N, N-diethylhydrazime, N, N-dibenzylhydrazine, N, N-diphenethylhydrazine, N-ethyl-N-benzyl-hydrazine, N-amino-1,2,3,4-tetrahydroisoquinoline, N- amino-pyrrolidine, N-aminotetrahydroisoindoline, N-amino-3-hydroxypiperidine and Namino-morpholine.

The reaction of the ketone or aldehyde with the hydrazine is conveniently carried out by bringing the reactants into contact with each other in the presence of water or a lower alcohol. The reaction takes place at room temperature, but a slightly elevated temperature can be used for the Oka-i8823 reaction rate. The isolation of the intermediate, the alkylidenylhydrazine or hydrazone, is suitably carried out according to conventional methods. Thus, the product, which usually consists of an oil in the form of the free base, can be salted out with an alkali metal hydroxide and extracted with a water-immiscible organic solvent such as ether. The product is easily isolated by distillation under reduced pressure.

The hydrazone obtained as an intermediate can be reduced to the corresponding hydrazine by the use of an appropriate reducing agent. Lithium aluminum hydride is preferably used as the reducing agent, but catalytic hydrogenation can also be used. With lithium aluminum hydride, the reduction is conveniently carried out by bringing the reactants into intimate contact with each other in an inert organic solvent such as anhydrous ether, dioxane or tetrahydrofuran. Elevated temperature, such as Aterflow temperature, increases the reaction rate. At reflux temperature, usually 1-8 hours are sufficient to substantially complete the reaction. When the reaction is complete, water can be added to the mixture to solidify the excess lithium aluminum hydride. To recover the product, the organic phase is separated off and the aqueous residue is extracted with the same solvent. The organic phase and the extracts can then be combined with each other and dried, after which the product is distilled.

Some hydrazines prepared therein, in addition to the above, having 2 carbon atoms between the hydrazine group and the amine group, Oro 1- (N-2-pyridylmethyl-N-methylaminoethyl) -2-N ', N'-dimethylhydrazine, 1- ( N-2-thienylmethyl-N-methylaminoethyl) -2-N'-methylhydrazine, N- (benzylaminoethyl) -N-morpholinoamine, N- (N-phenylisopropylN-ethylaminoethyl) -NcN'-di-benzyl -hydrazine, N- (2-tenylaminopropyl) -NcN'-dipropyl-hydrazine, N- (2-pyridylethylaminoethyl) -N-pyrrolidinoamine and N-benzylaminoethyl, N7-dihydroxyethylhydrazine.

The hydrazines in which R 1 and R 2 are other substituents can be converted into compounds of formula I, which in R 1 form an alkyl or aralkyl group, by reductive alkylation using a formaldehyde formic acid mixture or an alkyl or aralkylacyl halide or an equivalent ester to form an acylhydrazine as an intermediate, after which the acyl group is reduced to an alkyl or alkylene group. This procedure can be ash-damaged by the following reaction formula: x7 / 1:13 R, COA R, Ar-Y-N-Z-N-N / R, C = O RI / R, Ar-Y-N-Z-N-N R 1, R 2, R 3, R 5, R 5, R 5, R 5, R 5, R 5, R 8, R 8, R 8, R 8, R 8, R 8, R 8, R 8, R 8, R 8, R 4, R 4, R 4, R 4, R 4, chlorine, bromine or iodine, or a lower alkoxy group, and R, represents a lower alkyl group, aryl group (phenyl group) or aralkyl group (phenyl-lower-alkyl group) and Z represents -B-CH-, in which B and R, R previously stated meaning.

In addition to the formaldehyde formic acid mixture which can be used to introduce a methyl group such as the group R in formula I, an alkyl formate can also be used to introduce a formyl group which can then be reduced, for example with platinum and Irate or with lithium aluminum hydride, to a methyl group .

Other esters or acyl halides may also be used to introduce the acyl group into the intermediate. Examples of such reactants are acetyl chloride, propionyl bromide, benzoyl chloride, phenylacetyl chloride, ethylphenyl acetate, phenylpropionyl chloride, methyl acetate and the like.

The acylation reaction is carried out by contacting the reactants in an inert solvent such as ether or tetrahydrofuran, after which the mixture is refluxed. The reduction of the acyl hydrazine formed as intermediate is easily carried out without isolating the acyl compound by using lithium aluminum hydride or by catalytic hydrogenation. Examples of some compounds which are prepared in this way are N- (benzylaminoethyl) -N-methyl-N ', N-dimethylhydrazine, N- (phenethylaminopropyl) -N-phenethyl-N-morpholinoamine and N- (N-benzyl-N-ethylaminoethyl) -N-ethylN ', N'-dihydroxyethylhydrazine.

Acid addition salts of the new hydrazines are prepared by contacting the hydrazine with a mineral acid or an organic acid. For example, such acids as hydrochloric acid, formic acid, maleic acid, fumaric acid and citric acid can be used to prepare salts of the hydrazines.

The hydrazines can be administered to humans and animals in the form of pure compounds. However, it is advisable to first combine one or more of the new compounds with a suitable pharmaceutical carrier, so as to obtain a more satisfactory ratio between the size of the preparation and the dose.

Pharmaceutical carriers in liquid or solid form can be used. Like liquid bars, water was aptly used. The produced los, 4— - nings can, if desired, be continued with flavoring agents.

For the preparation of powders, solid pharmaceutical carriers such as starch, sugar, talc and the like can be used. The powders can be used in the form obtained for direct administration to a patient or the powders can also be added to suitable footwear and water shoes, such as water, to facilitate administration.

The powders can also be used for the preparation of tablets or for the filling of gelatin capsules. Suitable lubricants, such as magnesium stearate, binders, such as gelatin, disintegrants, such as sodium carbonate in combination with citric acid, may be used in the manufacture of the tablets.

Unit dosage forms, such as tablets and capsules, may contain a suitable, predetermined amount of one or more of the hydrazines, preferably in the form of a non-toxic acid addition salt, and may be administered in a number of one or more at a time at regular intervals. However, such unit dosage forms should generally contain 0.1 to 10% by weight of the active hydrazines.

A typical tablet may have the composition: 2- (N-benzyl-N-methylamino) - Mg ethyl hydrazine Starch of pharmacopoeia grade 57 Pharmacopoeia grade lactose 73 Pharmacopoeia grade talc 9 Stearic acid 6 Powders 1, 2 and 3 are mixed and granulated, after which the granules are mixed with powders 4 and 5 and tableted.

Capsules can be prepared by filling hard gelatine capsules No. 3 with the following ingredients in a careful mixture: N-3-pyridylmethyl-N-methylamino-Mg 2-propyl-hydrazine Pharmacope-grade lactose 200 lamply orally.

According to a further embodiment of the invention, one or more of the hydrazines is administered simultaneously with or in connection with the administration of tryptophan and / or phenylalanine to humans or animals. Tryptophan crosses the blood barrier in the brain and is transferred in the brain to serotonin. Serotonin is not administered directly, as it cannot cross the blood barriers of the brain. Similarly, phenylalanine crosses this barrier and is transferred to the brain to norepinephrine. Norepinephrine cannot cross the blood barrier in the brain and is therefore not given directly. By administering an active hydrazine concomitantly with or in conjunction with tryptophan or tenylalanine, it inhibits or prevents the monoamine oxidase inhibitory activity of the hydrazine degradation of serotonin and / or norepinephrine produced in the brain by said amino acids. The serotonin and norepinephrine content is thereby increased and is also maintained at the desired level through the treatment described.

Any appropriate amount of tryptophan and / or phenylalanine may be administered as these substances are not toxic. One or both of these substances may conveniently be combined with one or more of the active hydrazines of suitable pharmaceutical preparations L.

The invention is further illustrated by the following examples, the temperatures are given in degrees Celsius.

Example 1. 2- (N-methyl-N-benzyl-amino) -ethylhydrazine - CH 2 N-C 2 H NHNH, / 4 CHB To 168 g (2.85 mol) of 85% hydrazine hydrate in 200 ml of boiling methanol 104.7 g (0.475 mol) of N-benzyl-N-methylaminoethyl chloride hydrochloride were added to 250 ml of methanol. The mixture was stirred and boiled for 3 hours under reflux, after which the methanol was distilled off and the residue was taken up in water. The aqueous solution was adjusted to a strongly alkaline reaction with solid potassium hydroxide and extracted with ether. The ether extracts were dried over potassium carbonate and evaporated, after which the product was distilled at 84-9770.2 mm; yield 53 g (62%); n = 1.5431.

C 101117N 3 Calculated: N 15.73 NN / This compound was prepared from N-3-pyridylmethyl-N-methyl-amino-2-propyl-bromide and an excess of hydrazine in the same manner as Example 1; boiling point 120-122'70.3 mm.

Example 3. 2- (N-methyl-N-benzylamino) -ethylethylidenyl-hydrazine. 54.4 g (0.2 mol) of N-methyl-N-benzylaminoacetal were hydrolyzed by slow addition while cooling to 275 g of concentrated hydrochloric acid. The mixture was cooled above the surface and then evaporated to dryness in vacuo. 50 ml of water were added to the residue and then 20% sodium hydride solution to pH 7. The product was dissolved in 100 ml of methanol and the methanol solution was added with stirring to 47 g (0.8 mol) of 85% hydrazine hydrate in 250 ml of methanol. The reaction mixture was allowed to stand overnight at room temperature, after which part of the solvent was distilled off. After adding 400 ml of water, the mixture was adjusted to strong Found: N 15.27 The corresponding dihydrochloride had a melting point of 184-187 °.

Example 2. N-3-Pyridylmethyl-N-methylamino-2-propyl-hydrazine - CH 2 N —CH 2 CH (CH 3) —NH — NH 2 CH 3 - - alkaline reaction with potassium hydroxide, then extracted with a total of 400 ml of ether and dried over anhydrous potassium carbonate. The ether was distilled off and the residue was fractionated through a 76 mm diameter column. Yield 27.3 g (77%); boiling point 10 / 1.0 mm; = 1.5522.

Calculated: N 15.73 Found: N 15.91 Example 5. 2- (N-methyl-N-benzylamino) -ethylhydrazine dimaleate.

A solution of 5.4 g of the base in 30 ml of ether was added to a solution of 8.1 g of maleic acid in 75 ml of ethanol. Yield 6.8 g; melting point 124-125 °.

CisH2aN2O3 Calculated: Maleic acid 56.42 N 6.81% Found: Maleic acid 57.91 N 6.83% Example 6. N-2- (N'-o-chlorobenzyl-N'-methylamino) -ethylhydrazine. 34 g (0.125 mol) of N-methyl-N-o-chlorobenzylaminoacetal were added to 65 ml of concentrated hydrochloric acid at 5-10 °. The excess acid and water were distilled off in vacuo by heating in a water bath, the temperature of which was 50 °. The residue was diluted to a volume of 125 ml with water and neutralized to pH 7 with 17 ml of 10% sodium hydroxide solution. The resulting solution was added to 36.7 g (0.625 mol) of 54.5% hydrazine at 0 and allowed to stand. Overnight. The solution was then quenched with sodium hydroxide under cooling, the warp oil was extracted with 3 x 75 ml ether. The extracts were briefly dried over potassium carbonate and the solvent was distilled off through a 12.7 cm column. The residue weighed 25 .mu.g, corresponding to a 95.3% yield.

To 5.7 g (0.15 mol) of lithium aluminum hydride in 150 ml of tetrahydrofuran was added a solution of the hydrazone 1100 ml of tetrahydrofuran Mom 20 minutes. The mixture was boiled for 3 hours under atherfkide, after which the complex was probed with 25 ml of 40% potassium hydroxide solution. The salts were filtered off and washed with tetrahydrofuran. The extract was dried over potassium carbonate, after which the solvent was distilled off through a 12.7 cm column. The residue was distilled in vacuo; boiling point 83-87 ° / 0.015 mm; yield 7.45 g; nfa 1.5394.

CH16 N3Cl Calculated: N6, Found: N 6.39 Example 7. N-2- (N'-o-chlorobenzyl-N'-methylamino) -ethylhydrazine dimaleate.

To 7 g (0.06 mol) of maleic acid, at least 150 ml of ethanol, was added a solution of 6.45 g (0.03 mol) of the base in 50 ml of anhydrous ether. The solid subsLansea was filtered off, washed with alcohol, dried and weighed. Yield 6.75 g (50.3%); melting point 121-122 °.

C13 / 24N3C2 Calculated: N 6.28 Found: N 6.33 Acid equivalent weight: Calculated: 111.46 Found: 107.48 Example 8. 1- (N-benzyl-N-methylaminoethylidenyl) -NcNi-dimethylhydrazine.

-CH 2 N-CH 2 CH = NN (CH 2) 2 CH 3 To 32.6 g (0.20 mol) of N-benzyl-N-methylaminoacetaldehyde hydrochloride 1150 ml of water was added 12.0 g (0.20 mol) of N, N-di -methylhydrazine, after which the mixture was stirred for 16 hours at room temperature, adjusted to a strongly alkaline reaction with solid potassium hydroxide and extracted with ether. The ether solution was used in the experiment described in the following Example 9.

Example 9. 1- (N-Benzyl-N-methylaminoethyl) -N ', 1,1'-dimethylhydrazine.

The ether solution of the ethylidene derivative obtained according to Example 8 is reduced with 7.6 g (0.20 mol) of lithium aluminum hydride in the usual manner; boiling point 110-112 ° / 0.50 mm.

Example 10. N- (1-phenyl-2-propyl) -aminoethyl chloride hydrochloride. <›- CH2-CH (C112) -Nli-C21-14C1 HCl To a round-bottomed three-necked flask with a volume of 500 ml and equipped with a jacket, stirrer, cooler and gas inlet tubes, was added 80 g (0.45 mol) of N- (1 -phenyl-2-propyl) -aminoethanol in the form of a solution in 180 ml of chloroform. Anhydrous hydrogen chloride was then allowed to bubble through the solution until it had assumed a pH of 2.0. The solution was heated and continued dropwise with 119 g (1.0 mol) of thionyl chloride, the solution taking on a black color. After completion of the thionyl chloride addition, the solution was boiled for 2 hours under reflux. The chloroform was evaporated in vacuo to give 115 g (0.45 mol) of a brown, oily residue.

Example 11. N- (1-phenyl-2-propyl) -aminoethylhydrazine.

CF 1 N 3 Calculated: N 7.90 Found: N 7.97 Example 4. 2- (N-methyl-N-benzylamino) -ethylhydrazine.

5.3 g (0.14 mol) of lithium aluminum hydride in 200 ml of dry ether were introduced into a 500 ml flask, followed by a solution of 25.5 g (0.144 mol) of 2- (N-methyl-N-benzylamino) -ethylidenyl-hydrazine in 100 ml of dry ether, Mom was added for 15 minutes. The reaction was exothermic. Stirring and refluxing of the reaction mixture was continued for 4.5 hours. Then a 40% aqueous solution of potassium hydroxide was added to probe the lithium aluminum hydride complex and the liquid was decanted. The product was rinsed with ether and dried over anhydrous potassium carbonate. The solvent was distilled off and the product was fractionated through a 76 mm column. Yield 16.2 g (63%); boiling point 101 ° / 0.05 mm; n = 1,543.

CloHrIN2 6— - <\ CH CH (C1-12) —NH — C2H4NH — NH, / 2 In a three-necked round-bottomed holy with a volume of 1 liter and equipped with a jacket, stirrer, cooler and dropping funnel, 132.75 g ( 2.25 mol / l) 85% hydrazine hydrate in 150 ml of methanol. The temperature was raised until the solution boiled under reflux. The refluxing solution was continued dropwise with a solution of 1 g (0.45 mol) of N- (1-phenyl-2-propyl) -aminoethyl chloride hydrochloride in 250 ml of methanol, after which the solution was boiled for 10 hours under reflux. After concentration in vacuo, the resulting residue was dissolved in 250 ml of water. The aqueous solution was adjusted to alkaline reaction with potassium hydroxide and extracted three times with 100 ml of ethyl ether. The ether extracts were dried over anhydrous potassium carbonate and concentrated on a steam bath. The residue, which weighed 52 g (0.27 mol), was distilled through a 10.2 cm Vigreux column to give 27.5 g of product (50%), b.p. 121-12670.4 mm.

Example 12. N- (1-phenyl-2-propyl) -aminoethylhydrazine dihydrochloride.

C 2 -CH 2 -CH (CH 2) NH-C 2 H, -NH- -NH, 2 HCl 27.5 g (0.13 mol) of N- (1-phenyl-2-propyl) -aminoethyl-hydrazine were dissolved in 300 ml of ethyl ether, after which the solution was slowly continued while mixing and cooling with 75 ml of a 4,18-n ether solution of hydrochloric acid. A rubbery precipitate formed. The mixture was cooled and the ether was carefully decanted. The gummy precipitate crystallized from a mixture (1: 3) of isopropyl alcohol and acetonitrile and was filtered off, washed and dried in a desiccator. Yield 45 g; melting point (sintering at 135 °) 140-160 °. 45 g of the product were recrystallized from 200 ml of hot ethanol to give 20 g of product. The percentage yield was 54%. The center of gravity of the product (after sintering at 145 °) was 203 °. The product foamed at 210212 °.

C 11 H 24 N 3 Cl 2 Calcd: N 15.79 Cl 26.64% Found: N 15.42 Cl 26.47% In the following, some examples of other compounds prepared according to the invention are given. In this case, 0 denotes a benzene ring.

[N-methyl-N- (4-fluoro) -benzyl] -amino- Lyl-hydrazine 4-F-OCH 2 N (CH 3 C 2 N 4 NH — N1-12;

The hydrochloride melts at 191-192 °. 1- (N-methyl-N-benzylaminoethyl) -2-palmitoylhydrazine OCH 2 N (CH 2) C 2 H 4 NH-NHC- (CH 2) 14 -CH 3; boiling point 45-65 °.

The hydrochloride melts at 115 ° (probe division). 2- (N-methyl-N-3 ', 4'-methylenedioxybenzyl) -aminoethyl-hydrazine 3,4-CH 2 O 2 -O-CH 2 N (CHOC 2 H 4 NH-NH 2; b.p. 152-15770.60 μm. 2- (N-methyl-No-methylbenzyl) -aminoethyl-hydrazine o-CH 2 OCH 2 -N-C 21-14NH-NH 4, boiling point 93- 9470.15 mm The hydrochloride melts at 182-185 °. Np - methoxybenzyl) aminoethylhydrazine p-CH 2 OCl-12-N-G 2 H 4 -NH-NH 4, boiling point 1145 ° / 1.2 mm.

The hydrochloride melts at 188-190 °. 2- (N-methyl-N- m-methoxybenzyl) -aminoethylhydrazine m-CH 3 O 2N 2 (C113) C 2 H 4 NH-NH 2; boiling point 130-13670.6 mm The hydrochloride melts at 188-190 °. 2- (N-methyl-N-m-chlorobenzyl) -aminoethyl-hydrazine m-C1-OCH2N (CH2) C2H4NH-NH2; boiling point 133-138 ° / 1.0 mm The hydrochloride melts at 203-204 °. 2- (N-methyl-N-p-chlorobenzyl) -aminoethyl-hydrazine p-C10 CH 2 N (CH 2) C 2 H, NH-NH 2; boiling point 116 —119 ° 10.35 mm The hydrochloride melts at 183-185 °.

Claims (3)

Paten tansprak: A process for the preparation of aralkylaminoalkylhydrazines having a therapeutic effect, characterized in that there is prepared compounds of the formula, R 1, R 3, R 2, R 2 and R 3 represent an aryl group, R 1 represents vale, an alkyl, alkenyl radical , aralkyl, cycloalkyl group or a heterocyclic group substituted by an alkyl group of up to 5 carbon atoms, R 1 represents vate or an alkyl group having up to 5 carbon atoms, R 2 and R 2 are the same or different and represent vate, alkyl, aryl, aralkyl group , alkenyl, alkynyl, cyclo- / R 3 alkyl or acyl groups or groups, R 1 represents a cyclic secondary amino group, R 5 represents hydrogen or an alkyl group having up to 5 carbon atoms, Y represents an alkylene group having up to 5 carbon atoms and B represents an alkylene group having up to 5 carbon atoms, by reacting a compound of the formula Ar - Y — N — B — CH — X R 5 - van in X represents a reaction-derived halogen, with a compound of the formula R 3 -NH-NH 2 to formation of a compound of the formula Ar — Y — N — B — CH — N — NH, I R1 R5 R2 Modification of the process according to claim 1, characterized in (Wray, that an equation of the formula Ar — Y — N — B — C = O R, R, is reacted with a compound of the formula, R 3 H 3 N — N / —4 to a compound of the formula 3 Ar — Y — N — B — C = N — No. J. 4 R1R which is reduced to a compound of the formula, R3 Ar — Y — N — B — CH — NH — KR / R Request publications: Patent ter frdn Great Britain 581 15 3. Other publications: Angewandte Chemie 71 (1959): H.2, pp. 87-88.