DE1768297B1 - Substituted alkylenediamines and their salts - Google Patents

Description

1 2.

The invention relates to new, therapeutically useful substituted alkylenediamines in general formula

CH-A ¹ -NH-B-NH-A ² -CH

X3

in which R _{1 is} an unsubstituted phenyl or cyclohexyl _{radical, R 2 is} a phenyl radical which can be substituted by a chlorine atom, a p-methyl or a p-dimethylamino group or by two hydroxyl groups or two methoxy radicals, A ¹ and A ² may be the same or different and mean straight or branched alkylene groups with 1 to 3 carbon atoms or stand for a direct bond and B represents a straight or branched alkylene chain with 2 to 4 carbon atoms or for a

- CH ₂ - CH (OH) - CH ₂ group

stands, and their physiologically acceptable acid addition salts.

The new compounds and their acid addition salts are characterized by a strong coronary dilatation Effect. In animal experiments, they have proven themselves to be familiar with regard to their effectiveness Constitution-like N- [3'-phenyl-propyl- (2 ')] -1, l-diphenylpropyl- (3) -amine, which is also coronary dilatoric (international abbreviation: prenylamide) has been shown to be clearly superior.

The coronary dilatory effect of the new compounds is largely selective and is through a parallel hypotensive component is not impaired. The coronary mechanism of action as such, it does not come about through an increase in the metabolism of the heart, as it does for others known, similar-acting cardiac agents is assumed. The lower effective dose on the cat, with which an increase in the coronary blood flow can still be achieved, is intravenous Administration of the new substances at only about 0.25 mg / kg body weight.

This minimum value is not or only in approximately reached in individual cases. Even after intraduodenal administration of the new substances increased coronary blood flow is also achieved. Side effects of a central nature could be observed with administration of the new substances according to the invention not observed even over a longer period of time will.

The superiority of the new substituted alkylenediamines according to the invention compared to the known constitution-like N- [3'-phenyl-propyl- (2 ')] -1, l-diphenyl-propyl- (3) -amine can be seen from the following table, in which the results of comparative tests in cats with a completely intact cardiovascular system after intravenous and intraduodenal Administration of the substances to be tested are listed. The comparative examination of the selective The vascular effect of the coronary active substances was carried out by continuous measurement of the Coronary blood flow (blood flow to the left ventricle) calorimetrically according to the in Naunyn-Schmiedebergs Archive for Pharmacology and Experimental Pathology, Vol. 255 (1966), p. 3, described procedure.

dose Maxi Duration until Maxi Duration until times to the times Achievement of the Coronary Reach blood Baseline blood pressure Subcfanz mg / kg by- the pressure (intra to the river Initial acceptance venous) took by min 0.250 bleeding mm Hg 5 0.500 % min 35 1, something
enlarged O \ / O 110 15th 40 amplitude CH CH ₂ -CH ₂ -NH-CH ₂ -CH ₂ -NH-HC -2HC1 1,000. 110 20th 3-, enlarged
Amnlifiiiip 65 / lI 11 l · '11L U u w N- (3,3-diphenyl-propyl- (l)) - N '- (diphenyl-methyl) - 2,000 115 40 5, enlarged ethylenediamine dihydrochloride 75 amplitude 0.250 150 > 60 10 0.500 20th remains lowered 1,000 65 7th 20th 20th \ - / \ / \ /
CH-CH ₂ -CH ₂ -NH-CH ₂ -CH ₂ -NH-Hc -2HC1 2,000 75 10 40 remains lowered, ri </ X / \ ^ \ 60 > 60 40 enlargement 70 > 60 the amplitude N- (Diphenylmethyl) -N '- (3-p-chlorophenyl-3-phenyl-propyl- (l)) - ethylenediamine dihydrochloride

continuation

substance -NH-CH ₂ -CH ₂ -HC -3HC1
Y3 CH-CH- -η
ι
CH ₃ CH ₃ dose
mg / kg
(intra
venous) Maxi
times
corona
by-
foot to
took Duration bi
to the
Reach
the
Starting
by-
bleeding
min Maxi
times
blood
pressure
acceptance
mm Hg Duration until
Achievement of the
Baseline blood pressure
min N- (3-p-Dimethylaminophenyl-3-phenyl-propyl- (l)) - N '- (3,3-diphenyl-
propyl (l)) ethylenediamine trihydrochloride 0.250 30th 5 40 1 ^CH \ CH · CH ₂ ■ CH ₂ ■ NH · CH ₂ ■ CH ₂ · - 0.500
1,000 80
90 10
15th 50
50 2
7th CH ₃ \ / \
CH · CH ₂ · CH ₂ · NH ■ CH ₂ · CH ₂ · -,
CH ₃ O - <^ y /
CH ₃ O - NH · CH ₂ · CH ₂ · HC '''· 2HCl 2,000 120 40 80 17, enlarged
amplitude \ = / N, N'-bis (3,3-diphenyl-propyl- (1)) -2,3-diaminobutane dihydrochloride y— ^ 0.250 20th 5 35 1 \ / \
CH • CH ₂ • CH ₂ • NH • CH ₂ • CH (OH) • CH ₂ • -η 0.500
1,000
2,000 55
110
110 8th
15th
25th 40
40
40 5
14th
something under
Starting blood
pressure,
enlargement the amplitude /O - NH · CH ₂ · CH ₂ · HC · 2HCl \ /
N- (3 (3,4-Dimethoxyphenyl-phenyl) -propyl- (l)) - N '- (3,3-diphenyl-
propyl (1)) ethylenediamine dihydrochloride 0.250 90 15th 55 15th CH · CH ₂ · CH ₂ · NH ·
CX 0.500
1,000
2,000 95
120
70 25th
45
> 60 60
70
70 something about Aus
gangue blood pressure
30th
under starting - NH • CH ₂ • CH ₂ • HC • 2HCl blood pressure,
amplitude
enlarged N, N'-bis (3,3-diphenyl-propyl- (1)) -1, 3-diaminopropanol- (2) -dihydrochloride 0.250 20th 15th 25th 5 0.500
1,000 30th
70 19th
35 40
90 15th
25th 2,000 90 > 60 110 more gradual
Recovery

continuation

/O CY CH- CH ₂ CH ₂ NH CH ₂ CH ₂ -, HO / * \ / - NH · CH ₂ · CH ₂ ■ ■ HC 2HCl CH ₃ - CH ₂ • NH -CH ₂ -HC • 3HCl /O dose Maxi Duration bi S. Maxi- Duration until I-NH • CH ₂ • CH ₂ • HC • 2HCl N- (3 (3,4-dihydroxyphenyl-phenyl) -propyl- (l)) - N '- (3,3-diphenyl- \ / \ - NH ■ CH ₂ CH ₂ · · HC 2HCl times to the i paint Achievement of the N-ß.S-Diphenyl-propyl-tlB-N'-ß-cyclohexyl-S-phenyl-propyHl)) - OH propyl (l)) ethylenediamine dihydrochloride \ = / HN'-Bis-p ^ -diphenyl-propyl-fllj-ethylenediamine-hydrochloride corona Attainers Blood- Baseline blood pressure substance ethylenediamine dihydrochloride / T7 \ N-iS-p-Dimethylaminophenyl-S-cyclohexylpropyHl ^ -N-ß ^ -diphenyl- mg / kg by the . pressure ^ "\ CH-CH ₂ -CH ₂ -NH-CH ₂ -ι ethyl (l)) ethylenediamine trihydrochloride (intra river to Starting decreased venous) took by- min / "^ = / CH · CH ₂ · CH ₂ · NH · CH ₂ ■ CH ₂ · -, 0.250 bleeding mm Hg 7th CY 0.500 % min 10 10 1,000
2,000 45 8th 15th 12th
20th CH-CH ₂ -CH ₂ -Nh-CH ₂ -CH ₂ - -ι ■ 80 15 ' 45
80 80
110 27
50 0.250 0.5 0.500 15th 2 1,000 10 3 35 10 2,000 30th 7th 40 15th 4,000 40 15th 40 25, enlarged 60 22nd 50 amplitude 70 45 0.250 3 0.500 10 6th 1,000 35 7th 30th . ~ ■ ' 60 25th ~ 100 > 60 ■ ·· 0.250 1 0.500 40-50 4th 1,000 60 7th 40-50 10 2,000 120 10 60 18th 100 > 30 60 80 > 30

continuation

substance

Maxi Duration until times to the dose Coronary Reach by- the to the river Initial mg / kg took by (intra bleeding venous) % min 0.250 0 0 0.500 10 1 1,000 15th 8th 2,000 25th 4th dose mg / kg (intra- duo- denal) 10,000 25th 60 20,000 40 85 30,000 0 0

Maximum
Blood pressure
acceptance

mm Hg

Duration until

Achievement of the

Baseline blood pressure

CH ₃

N- (3'-phenyl-propyl- (2 ')) - l, l-diphenyl-propyl- (3) -amine (reference substance)

20th 25th 20th

1
1

longer lasting
Drop in blood pressure

CH-CH ₂ -NH-CH-CH ₂ NH-CH ₂ • CH ₂ -HC • 2HCl

0
15th

N- (3,3-Diphenyl-propyl- (l)) - N '- (2,2-diphenyl-ethyl- (l)) - ethylenediamine dihydrochloride

CH,

CH ■ CH ₂ ■ CH ₂ -NH-CH-CH ₂

N- (3'-phenyl-propyl- (2 ')) - l, l-diphenyl-propyl- (3) -amine (reference substance)

The substituted alkylenediamines according to the invention can be used as such, but preferably in In the form of their well-crystallizing acid addition salts, optionally with solid or liquid carriers common type mixed, for the preparation of solutions for injections and especially of Pharmaceutical preparations to be administered orally, such as coated tablets, pills or tablets, are used will.

The new compounds of the formula I can be used in various ways according to processes known per se Way to be made:

1. By reacting an alkylene dihalide with a diphenylalkylamine of the general formula

CH-A ¹ -NH ₂

(II)

will lead. The organic solvents used can preferably be low molecular weight alcohols will.

2. By reducing a compound of the formula I in which, however, one or more CH ₂ groups adjacent to the nitrogen atoms have been replaced by CO groups.

The reducing agent used is lithium aluminum hydride in an approximately four-fold excess, based on the molar ratio, and the reduction is preferably carried out in an organic solvent such as diethyl ether or tetrahydrofuran, carried out in such a way that the solution of the acid amide is cooled the lithium aluminum hydride suspension in the selected solvent is added dropwise and that The reaction mixture is then refluxed for several hours.

3. By reacting a diphenylalkyl halide of the general formula

60

in which R ₁ , R ₂ and A ^{1 have} the meaning given above, in a molar ratio of 1: 2 to 1: 4, the condensation advantageously being carried out without hydrogen halide acceptor in the presence or absence of an organic solvent at room temperature or at elevated temperature. CH-A ¹ - Shark

(III)

in which R ₁ , R ₂ and A ^{1 have} the meaning given above and the abbreviation Hai stands for a halogen atom

109 551/533

stands, with an alkylenediamine of the general formula

H ₂ NB-NH ₂

in which B also has the meaning given above, in the presence or absence of an organic solvent, such as ethanol, by refluxing for several hours if the reaction is in the presence an organic solvent is carried out, or at temperatures between 50 and 150 ° C, when working without a solvent.

4. By reacting aliphatic compounds which contain two C O groups and a total of 2 to 4 carbon atoms in the molecule with an amine of the formula II under reducing conditions, preferably using sodium borohydride (NaBH ₄ ) as the reducing agent. The mixture of the keto compound and the amine is first heated to a temperature of about 100 to 130 ° C, the azomethine formed as an intermediate product in this reaction is dissolved in a low molecular weight alcohol, the reducing agent is added to this solution with cooling and the resulting solution The reaction mixture is then refluxed for a few hours.

5. By reacting a compound of the general formula

CH-A ^ NH-B-NH ₂ (IV)

R>

in which R ₁ , R _21, A ^{1 and} B have the meaning given above, with a CO-containing compound of the type

35

CH-Y-CHO

40

45

CO

CH-Y — COCH,

55

60

in which Y is a straight or branched alkylene group or is a direct bond. The azomethines intermediate in this reaction can be reduced with sodium and alcohol, but preferably made using sodium borohydride as a reducing agent will.

65 When using sodium borohydride, the reduction is expediently carried out as described under 4; if, on the other hand, the reduction is to be carried out using sodium, the most favorable working conditions are obtained when the metal is present in a large excess and the process is carried out at the boiling point of the alcohol. Low molecular weight alcohols which have 2 to 5 carbon atoms in the molecule can be used as the alcohol for this purpose.

6. In the event that B in _{formula is the group -CH 2} -CHOH-CH ₂ -: by reacting an amine of the formula II with epichlorohydrin, in which the condensation with or without the addition of a halogen acceptor at elevated temperature without isolation of the intermediate in can be carried out in one process step. Appropriately, the reaction is carried out in such a manner that the epichlorohydrin to about four fold excess of amine, based on the molar ratio of the reactants at elevated temperature (about 10O ⁰ C) was added dropwise and the reaction mixture is then further heated for several hours.

7. By reducing a compound of the formula I, in which, however, deviating from the formula depicted and the meanings given for the symbols used therein, in the chains A ¹ , A ² and B there are unsaturated bonds and optionally. In addition, there are CO groups adjacent to the nitrogen atoms, using Raney nickel, noble metal catalysts or lithium aluminum hydride. If carbonyl groups and unsaturated bonds are also present in the molecule of the starting substance, lithium aluminum hydride must be used to carry out the reduction, whereby the same working conditions as described under 2 are preferably selected. The implementation of the reduction using Raney catalysts, on the other hand, is usually carried out at temperatures of about 20 to 100 ° C. under a pressure of about 50 to 100 atmospheres.

The respective reaction product is worked up in the customary manner and is not technical Trouble.

The new substituted alkylenediamines can after isolation and, if appropriate, purification in a manner known per se by dissolving the compounds in an organic solvent, such as B. alcohol, and subsequent precipitation with inorganic or organic acids in the appropriate Addition salts are transferred.

The preparation of the new invention Connections are explained in more detail below, for example.

Example 1

N, N'-bis (3,3-diphenyl-propyl- (l)) -ethylenediamine dihydrochloride

42 g (0.2 mol) of 3,3-diphenylpropylamine are added 110 ° C heated and while stirring at the same time within 80 minutes with 9.4 g (0.05 mol) Ethylene bromide added. To this mixture ml of ethanol are added and the reaction mixture then heated to dissolution. The resulting solution is mixed with 4 g of powdered sodium hydroxide added and the precipitated sodium

bromide filtered off. The solvent is then evaporated off under reduced pressure and the excess amine is distilled off from the resulting residue in an oil pump vacuum. The residue freed from the excess amine is then dissolved in ether and the ethereal solution shaken out with water. After drying the essential solution with sodium sulfate it becomes the solvent distilled off in vacuo and the residue dissolved in methanol. The one after the addition of ethereal Hydrochloric acid to this solution in methanol precipitated crystal slurry is sucked off fractionally, washed, dried and, if necessary, from a mixture of methanol and a little water recrystallized. It becomes N, N'-bis- (3,3-diphenyl-propyl- (l)) - ethylenediamine.2HCl with a melting point of 232 up to 233 ° C (after browning). Yield: 31%.

Example 2

N, N'-bis (4,4-diphenyl-butyl- (2)) -ethylene-

diamine dihydrochloride

A solution of 22.1 g (0.0465 mol) of N, N'-bis (4,4-diphenylbutyl- (2)) -glycine amide in 120 ml of absolute ether is added dropwise with cooling to a suspension of 3.8 g of lithium aluminum hydride in 280 ml of absolute ether are added. The reaction mixture is then refluxed for 6 hours cooked. After decomposition of the excess reducing agent with ethyl acetate and a little Water, the inorganic components are filtered off and washed several times with ether. The ether phases are then combined, dried with sodium sulfate and the solvent evaporated. The residue obtained is first precipitated as phosphate from alcoholic solution. The base freed from the precipitate by treatment with sodium hydroxide solution is then dissolved in Usually in the dihydrochloride of N, N'-bis (4,4-diphenyl-butyl- (2)) - ethylenediamine transferred, after recrystallization from isopropanol / ether and water has a melting point of 230 to 232 ° C. Yield: 20%.

The following new N, N'-bis (diphenyl-alkyl) alkylenediamines can be used analogously to the procedure explained in the preceding example are produced and isolated in the form of their well-crystallizing hydrochlorides:

Example 3

N-to-chlorophenyl-phenyl-methylJ-N'-ß ^ -diphenylpropyl- (l)) - ethylenediamine dihydrochloride

A solution of 23.4 g (0.05 mol) of N- (3,3-diphenyl - propyl - (I)) - (o - chlorophenyl - phenyl - methylamino) acetamide in tetrahydrofuran is added dropwise with cooling to a suspension of 3.8 g Lithium aluminum hydride in 100 ml of tetrahydrofuran was added. After boiling the reaction mixture for 5 hours the excess lithium aluminum hydride is decomposed with a little water under reflux, the inorganic portion filtered off and washed with ethanol. After concentrating the filtrate, the remaining Dissolved residue in ethanol and mixed with ethereal hydrochloric acid. The one who fails Precipitate is collected and recrystallized from ethanol / ether. The compound shows a melting point from 237 to 238 ° C. Yield: 18%.

Example 4

N- (3 (3,4-Dimethoxyphenyl-3-phenyl) -propyl- (l)) - N '- (3,3-diphenyl-propyl- (l)) - ethylenediamine-

dihydrochloride

26.1 g (0.05 mol) N - (3,3 - diphenyl - propyl - (1)) - (3,4-dimethoxy-phenyl-3-phenyl-propyl- (l) -amino) - acetamide are dissolved in 100 ml of tetrahydrofuran and, with cooling, to form a suspension of 3.8 g Lithium aluminum hydride added dropwise to 100 ml of tetrahydrofuran. After refluxing the reaction mixture for 3 hours and then decomposing it the excess lithium aluminum hydride is filtered and the solvent is distilled off. The residue obtained is then dissolved in ethanol and removed from the solution by adding in ethereal Hydrochloric acid precipitated the hydrochloride until the reaction was clearly acidic. After separation and recrystallization from ethanol / ether shows the dihydrochloride of N- (3 (3,4-dimethoxyphenyl - 3 - phenyl) - propyl - (I)) - N '- (3,3 - diphenylpropyl (I)) - ethylenediamine a melting point of 214 to 215 ° C. Yield: 48%.

Example 5

N, N'-bis (3,3-diphenyl-propyl- (1)) -2,3-diaminobutane dihydrochloride

N- (3,3-diphenyl-propyl- (l)) - N '- (diphenyl-

methyl) ethylenediamine dihydrochloride,

F. = 226 to 227 ° C. Yield: 26%;
N- (Diphenyl-methyl) -N '- (3-p-Chlorophenyl-

3-phenyl-propyl- (l)) - ethylenediamine-

dihydrochloride,

M.p. = 214 to 215 ° C. Yield: 18%;
N- (3-p-dimethylaminophenyl-3-phenyl-

propyl- (l)) - N '- (3,3-diphenyl-propyl- (l)) -

ethylenediamine trihydrochloride,

F. = 219 to 22O ⁰ C. Yield: 58%;
N- (3-p-methyl-phenyl-3-phenyl-propyl- (l)) -

N '- (3,3-diphenyl-propyl- (l)) -ethylenediamine-

dihydrochloride,

M.p. = 196 to 197 ° C. Yield: 38%;
N- (3-Cyclohexyl-3-phenyl-propyl- (l)) -

N '- (2,2-diphenyl-ethyl- (l)) -ethylenediamine-

dihydrochloride,

Mp = 207 to 209 ⁰ C. Yield: 12%.

A mixture of 10.5 g (0.05 mol) of 3,3-diphenylpropylamine and 2.6 g (0.03 mol) of diacetyl are heated to 120 ° C. for 2 hours. 50 ml of methanol are then added to the reaction mixture this is heated until the initially syrupy mass is dissolved. The cooled solution is added in portions 5 g of sodium borohydride are added with stirring, the mixture is stirred for a further 1 hour at room temperature and heated then at reflux temperature for 2 hours. Upon cooling, separates from the methanolic solution a brown oil off. After decanting off the oil, the solvent is evaporated off in vacuo and the residue formed is treated with a water-ether mixture. Then the The ether phase is separated off, dried with potassium carbonate and mixed with ethereal hydrochloric acid. The one with it precipitate (pale yellow crystals) is filtered off and extracted from an alcohol-ether mixture recrystallized. N, N'-bis- (3,3-diphenyl-

propyl - (I)) - 2,3-diaminobutane - dihydrochloride vom Melting point 248 to 249 ° G. From the brown oil previously separated by decanting, in in the manner described, further proportions of the compound can be obtained from the same melting point. Overall yield: 37%.

Example 6

N, N'-bis (3,3-diphenyl-propyl- (1)) -1, 3-diaminopropanol (2) dihydrochloride

A mixture of 22.2 g (0.105 mol) of 3,3-diphenylpropylamine, 3.2 g (0.035 mol) of epichlorohydrin, 6.9 g (0.05 mol) of potassium carbonate and 60 ml of n-butanol is kept at one temperature for 20 hours heated from 110 ^{0 C.} After this time has elapsed, the potassium carbonate is filtered off and the solvent is removed by evaporation in vacuo. The excess amine is first distilled off from the resulting residue in an oil pump vacuum, this is then taken up in ethanol and ethereal hydrochloric acid is added to the ethanolic solution until it becomes clearly acidic. The crystals of N ₅ N '- bis (3,3 - diphenyl - propyl - (I)) -1,3 - diaminopropanol (2) dihydrochloride which precipitate are filtered off and recrystallized from ethanol / ether. Melting point: 217 to 218 ° C. Yield: 15%.

Example 7

N-ß ^ -Diphenyl-propyHl ^ -N'-ß-cyclohexyl-3-phenyl-propyl- (l)) - ethylenediamine dihydrochloride

A solution of 5.8 g (0.017 mol) of N- (3,3-diphenyl-propyl- (I)) - (3-cyclohexyl-3-phenyl-propyl- (1)) -acetamide in 65 ml of absolute ether, while cooling, a suspension of 1.3 g is added dropwise (0.035 mol) lithium aluminum hydride in 75 ml of absolute ether was added and the reaction mixture then heated under reflux for 6 hours. After adding a little water to decompose the Excess lithium aluminum hydride, the inorganic material is filtered off and treated with ethanol rewashed. The solvents are evaporated from the filtrate and the residue is dissolved in methanol solved. To convert the base into the hydrochloride ethereal hydrochloric acid is added to the methanolic solution and the precipitated crystals are separated off and recrystallized twice from a methanol-ether mixture. The compound obtained shows a Melting point from 192 to 193 ° C. Yield: 17%.

Example8

N, N'-bis (3,3-diphenyl-propyl- (l)) -ethylenediamine dihydrochloride

A solution of 13.3 g (0.029 mol) of N, N'-bis (3,3-diphenylpropen (2) yl) glycine amide in 75 ml of tetrahydrofuran is cooled and with constant stirring to form a suspension of 2.2 g (0.058 mol) of lithium aluminum hydride in 75 ml of tetrahydrofuran was added dropwise. The reaction mixture is then refluxed for 5 hours and then the excess reducing agent is decomposed by carefully adding water while cooling with ice. After filtering off the inorganic components and washing with ethanol, the solvent is evaporated off in vacuo, the residue is dissolved in ethanol and ethereal hydrochloric acid is added to form a salt. After a few hours the new compound crystallizes out. F. = 230 to 231 ^° C. Yield: 18%.

Example 9

N, N'-bis (3,3-diphenyl-propyl- (l)) -ethylenediamine dihydrochloride

2.7 g (0.01 mol) of 3,3-diphenylpropyl bromide will be used dissolved in 10 ml of ethanol and refluxed with 0.6 g (0.01 mol) of ethylenediamine for 8 hours. After adding 20 ml of 2N sodium hydroxide solution to the reaction mixture, it is extracted with ether and after evaporation of the solvent from the residue in an oil pump vacuum, the excess starting product removed. The residue is then taken up in ethanol and the resulting Solution acidified with essential hydrochloric acid. The precipitated crystals are suction filtered and off Recrystallized ethanol. In 21% yield, N, N '- bis (3,3 - diphenyl - propyl (I)) - ethylenediamine 2HCl obtained, which shows a melting point of 230-231 ° C.

Example 10

N- (3,3-Diphenyl-propyl- (l)) - N '- (2,2-diphenylethyl- (l)) - ethylenediamine dihydrochloride

A mixture of 2.5 g (0.01 mol) of N- (3,3-diphenylpropyl- (l)) - ethylenediamine and 1.96 g (0.01 mol) of diphenylacetaldehyde is brought to a temperature of ^{I 1} Z _{2 hours} heated from 120 to 13O ⁰ C. After cooling, 25 ml of methanol are added and the mixture is stirred until it dissolves. Then 1.5 g of sodium borohydride are added in small portions to the reaction mixture with stirring and this is then refluxed for 3 hours.

After adding 40 ml of 2N hydrochloric acid, the alcohol is distilled off in vacuo and the remaining aqueous phase is extracted twice with ether. It is then made alkaline with potassium carbonate and the base formed is dissolved in ethanol. The hydrochloride is precipitated by adding ethereal hydrochloric acid to the solution of the base in ethanol and fractionally recrystallized after separation. It is N- (3,3-diphenyl-propyl- (l)) - N '- (2,2-diphenyläthyl- (l)) - ethylenediamine dihydrochloride of melting point 206-207 ⁰ C. Yield: 16%.

Example 11

N- (3 (3,4-dihydroxyphenyl-phenyl-propyl- (l)) - N '- (3,3-diphenyl-propyl- (l)) - ethylenediamine-

dihydrochloride

2 g (0.0039 mol) N- (3 (3,4-dimethoxyphenyl-3-phenyl-propyl- (l)) - N '- (3,3-diphenyl-propyl- (l)) - ethylene- diamine are dissolved in 12 ml of glacial acetic acid, which contains 40% hydrogen bromide, in a carbonic acid atmosphere refluxed. After cooling, the reaction mixture is diluted with 50 ml of water, alkalized with potassium carbonate and then extracted twice with chloroform. The chloroform phase is then dried over potassium carbonate and the solvent evaporated. After solving the remaining residue in methanol falls after the addition of ethereal hydrochloric acid to the methanolic Dissolve the dihydrochloride, which after separation and recrystallization from methanol-ether form a

Claims (1)

15 16 Shows melting point of 182-184 ° C. Yield: the one obtained by a chlorine atom, a p-methyl or 32%. a p-dimethylamino group or by two Claim: hydroxyl groups or two methoxy groups sub- ",,.,.,.",,. . j ,,. can be substituted, A ¹ and A ^{2 are} identical or different Substituted alkylenimines of the general _{five can be and undelayed or mixed} . ^m branched alkylene groups with 1 to 3 carbon R ₁ rf V mean atoms or for a direct bond \ ■ / \ = / stand and B an unbranched or branched one CH-A ¹ —NH-B — NH-A ² —CH alkylene chain with 2 to 4 carbon atoms. \ / ~~ \ ^I0 or for a _ CH ₂ - CH (OH) - CH ₂ group in which R _{1 is} an unsubstituted phenyl or, and its physiologically acceptable acid Cyclohexyl radical, R ₂ denotes a phenyl radical, addition salts. 109 551/533