DE2511022C3 - N- (3,3-Diphenylpropyl) -N '-benzylpiperazines - Google Patents

Description

benzyl) piperazine and its salts.

4. N- (33-Diphenylpropyl) -N '- (2,3,4-trimethoxybenzyl) -piperazine and its salts.

5. N- (3,3-Diphenylpropyl) -N '- (3,4,5-trimethoxybenzyl) -piperazine and its salts.

The invention relates to N- (3,3-DiphenylpropyI) -N'-benzylpiperazines of the general formula

(OCH ₃ I _n

CHCH ₂ CH ₂ -N N-CH ₂ - <f

in which η represents an integer from 0 to 3 and salts thereof.

The previously known piperazine derivatives with an effect on the coronary blood flow have in this respect Disadvantages than they are either in terms of the increasing effect on the coronary blood flow [ED5o (mg) = dose which can increase the coronary blood flow by 50%] too weak or with regard to the Toxicity are too strong to be put into practical use as remedies for humans. In fact, only one compound is used today, namely trimetazidine dihydrochloride [1- (23,4-trimethoxybenzyl) piperazine dihydrochloride)] manufactured as a human medicine

The aim and object of the invention was therefore the production of medicaments which contain the trimetazidine dihydrochloride far surpassed in its increasing effect on the coronary blood flow; to this end, the inventors undertook extensive studies over many years, which finally to find and to produce the inventive; Compound (I).

The compounds of the invention (1) are novel compounds which have not been described so far and because of their exceptional pharmacological

Table 1

see activity as valuable drugs.

In order to illustrate the pharmacological action of these compounds, comparative tests were carried out with regard to the increasing effect on the coronary blood flow carried out on rabbits measured using the Langendorff method

as well as for acute toxicity using trimetazidine dihydrochloride as a control compound; the results are shown in Table 1. The Langendorff method was based on the in Folia Pharmacologica Japonica, Rd. 56, p. 1387 (1960)

method described and the acute toxicity by injection into the peritoneal body cavities measured by mice.

From the results shown in Table I it can be seen that the invention

Compounds (I) by a factor of 10 or more to the trimetazidine dihydrochloride in the increasing effect are superior to coronary blood flow; their acute toxicity (LDsomg / kg) is 20-30%, so that they lack strong toxicity.

Nevertheless, it is quite obvious that the compounds (I) according to the invention have a medicinal effect show in amounts considerably less than that of the trimetazidine dihydrochloride.

Results of comparative tests with compounds of the invention and trimetazidine dihydrochloride regarding the increasing effect on the coronary blood flow (EDw.mg) and the acute toxicity (LD50, mg / kg)

Tested connections

Edeo
(mg)

LDso

(mg / kg ip mouse
Inject. into the peritoneal body cavities)

N- (3,3-diphenylpropyl) -N '- (3,4,5-trimethoxy-0.06

benzylpiperazine dihydrochloride

N- (3,3-diphenylpropyl) -N '- (3,4-dimethoxy-0.05

benzylj-piperazine dihydrochloride

89
66

25th

11th

continuation
Tested connections

EDw (mg)

(mg / kg ip mouse injections into the peritoneal Body cavities)

N- (3,3-Diphenylpropyl) -N '- (2,3,4-trimethoxybenzyl) -piperazine dihydrochloride

N- (3,3-Diphenylpropyl) -N'-benzy] piperazine dihydrochloride

Trimetazidine dihydrochloride
(Control connection)

The preparation of the compounds according to the invention is shown in the following equation: carried out according to known methods:

0.02 (00 0.08 101 0.80 390

CHCH ₂ CH ₂ N 'nH (CH ₃ O),

(II)

CH ₂ X

(D

CHCH, CH, X

(IV)

in which the symbol X is a halogen atom and π is an integer from 0 to 3

The compounds of the general formula (I) according to the invention can be obtained by subjecting benzyl halides or methoxy-substituted benzyl halides of the general formula III to a condensation reaction with N-3,3-diphenylpropylpiperazine of the formula (II) in equimolar amounts or in a slight excess. The condensation reaction will, in a solvent at reaction temperatures below 28O ⁰ C and reaction times of less than 30 hours. If the reaction is preferably carried out under such conditions that the reaction temperature is 1-25 hours 50-200 ⁰ C and the reaction time, the desired compound in high yields of 70% or above can be obtained. In addition, in this condensation reaction it is also preferred to use a dehydrohalogenating agent such as tertiary amines (e.g. trimethylamine, ethylamine, tripropylamine, tributylamine, triamylamine, etc.) or metal carbonates, e.g. B. alkali metal carbonates, alkaline earth metal carbonates and heavy metal carbonates are added as basic condensing agents. That is, when this condensation reaction is carried out in the presence of a dehydrohalogenating agent, lowering of the reaction temperature, shortening of the reaction time and other effects can be achieved.

Halides of the general formula ΠΙ include chlorides and bromides Examples of solvents are alcohols with no more than 12 carbon atoms, halogenated hydrocarbons, Hydrocarbons, ketones, esters, ethers, nitrogenous compounds and sulfurous ones Mentioned compounds which can be used individually or in the form of a mixture.

The desired compounds (I) can also be obtained by reacting 33-diphenylpropyl halides of the general formula (V) with an N-aralkylpiperazine of the general formula (IV) can be obtained in equimolar amounts or in a slight excess thereof Such halides of the general formula V are again the chlorides and bromides. the Implementation can be done under the same conditions as in the case of using the above written methoxy-substituted benzyl halides of the general formula (III) are carried out.

The compounds of general formula (I) obtained by the process of the invention are main ones oily substances in the state of the free base. If necessary, they can be moved to the more expedient Handling using inorganic or organic acids, such as chlorinated water

chemical acid. Sulfuric acid, lactic acid, citric acid, Malic acid, succinic acid and fumaric acid can be converted into rapidly crystallizing acid addition salts.

example 1

Preparation of N- (33-Diphenytpropyl) -N'-benzylpiperazine dihydrochloride

To a 17.62 g (0.1 mol) of N-benzylpiperazine in 100 ml of xylene-containing solution were 23.05 g (0.1 mol) of 3,5-diphenylpropyl chloride and 10.1 g (0.1 mol) Triethylamine added and the resulting solution heated at reflux temperature for 2.5 hours. The reaction liquid was allowed to cool and the precipitated Triethylamine hydrochloride filtered off. Then dry hydrogen chloride gas was passed through the solution while the solution was cooled to

N- (3,3-DiphenylpropyI) -N'-benzyipiperazine dihydrochloride to precipitate. The crystals were collected by filtration and recrystallized from an ethanol / ether mixed solvent to obtain 37.7 g of pure crystals (85% yield), m.p. 187-188 ° C.
Elemental analysis:

BeHaIsC ₂₆ H ₃₂ N ₂ Ct ₂ ( ⁰ Zo):

C 70.42; H 7.27; N 632;

found (%):

C 70.26: H 7.13; N 6.48.

B e i s ρ i e 1 2

Preparation of N- (33-Diphenylpropyl) -N'-benzylpiperazine dihydrochloride

1.76 g of N-benzylpiperazine (0.01 mol), 2.3 g (0.01 mol) of 3,3-diphenylpropyl chloride, 1.5 g (0.015 mol) of calcium carbonate 3: 5 carbonate and 2 ml of dimethyl sulfoxide were added with 20 ml of sec Butanol mixed and the resulting solution heated at reflux temperature for 2.5 hours. The reaction liquid was filtered after cooling, the filtrate was concentrated under reduced pressure to obtain an oily residue, which was partitioned with ether and water; the ether layer was dried and then dry hydrogen chloride gas was bubbled through the ether solution while cooling the solution to precipitate 1- (33-diphenylpropyl) -4-benzylpiperazine-4: 5 dihydrochloride, the crystals of which were recrystallized from methanol to give 3.6 g (81 , 2% yield) pure crystals with melting point 187-188 ° C to be obtained.
Elemental analysis:

Ber. as C ₂₆ H ₃₂ N ₂ Cl ₂ (%): ψ

C 70.42; H 7.27; N 6.32;

found (%):

C 70.45; H 7.31; N 6.34.

B e i s ρ i e 1 3

Preparation of N- (3,3-diphenylpropyl) -N'-ben3 »ylpiperazine dihydrochloride and difumarate

2.8 g of N-3,3-diphenylpropylpiperazine (0.01 mol) and 1.3 g (0.01 mol) of benzyl chloride were in a mixed solution solvent from 20 ml of toluene and 10 ml of isopropyl alcohol and the resulting solution at reflux temperature Heated for 4.5 hours. The reaction liquid was cooled and added with ether that with hydrogen chloride was saturated to precipitate N- (3,3-diphenylpropyl) -N'-benzylpiperazine dihydrochloride. The crystals of this salt were recrystallized from a mixed solvent of ethanol and ether to give 3.75 g (84.6% Yield) pure crystals with a melting point of 187-188 ° C.

Elemental Analysis ·.

Calculated as C ₂₆ H ₃₂ N ₂ CbW:

C 70.42; H 7.27; N 632;

found (%):

C70.bl: H 7.32: N 635.

The above-mentioned dihydrochloride in an amount 2.7 g (0.0061 mol) was dissolved in 10 ml of water; this solution were 20 ml of a 10proz. Sodium hydroxide solution The resulting solution was extracted three times with 10 ml of ether each time Ethereal layers combined, washed with water and dried. By adding a methanol-ether solution from 1.75 g (0.015 mol) of fumaric acid to this ethereal solution, 3.7 g (95.0% yield) of N- (3,3-di-

phenylpropyl) -N'-benzylpiperazine difumarate dihydrate
with a melting point of 209-210 ° C. (decomp.).
Elemental analysis:

Ber. as CmH ₃₈ N ₅ O ₈ · 2 H ₂ O (%):

C 63.94; H 6.63; N 439;

found (%):

C 64.02: H 636; N 434.

Example 4

Preparation of N- (3,3-Diphenylpropyl) -N '- (3.4-dimethoxybenzyl) -piperazine dihydrochloride

11.8 g of N-3,4-dimethoxybenzylpiperazine (0.05 mol). 11.5 g (0.05 mol) of 3,3-diphenylpropyl chloride and 5.05 g (0.05 mol) of triethylamine were dissolved in 100 ml of xylene and reacted as in Example 1; 18.4 g of N- (3,3-diphenylpropyl) -N '- (3,4-dimethoxybenzyl) piperazine dihydrochloride (73.1% yield) with a melting point of 184 ° C. were obtained.
Elemental analysis:

Ber. as C ₂₈ H ₃₆ N ₂ O ₂ Cl ₂ ^ o):

C 66.79; H 7.21; N 5.56;

found (%):

C 66.48: H 6.90; N 5.54.

Example 5

Preparation of N- (33-Diphenylpropyl) -N '- (3,4-dimethoxybenzyl) -piperazine dihydrochloride

2.36 g of N-3,4-dimethoxybenzylpiperazine (0.01 mol), 2.75 g (0.01 mol) of 33-Diphenylpropylbromtd and 1.1g (0.011 mol) of triethylamine were in a mixed solvent of 10 ml of pyridine and 10 ml of benzene and the resulting solution heated at reflux temperature for 1.5 hours. The reaction liquid was filtered after cooling and the filtrate was concentrated under reduced pressure to obtain a colorless, transparent, oily substance, which was extracted by shaking after adding ether and water. The ether layer was dried and then, while cooling the liquid, dry hydrogen chloride gas was passed through the liquid to precipitate N- (33-diphenylpropyl) -N '- (3,4-dirnethoxybenzyl) piperazine dihydrochloride. The salt crystals were recrystallized from a methanol / ether mixed solvent to obtain 4.16 g of pure crystals (82.6% yield) having a melting point of 184 ° C.
Elemental analysis:

Ber. as C ₂₈ H ₃₆ N ₂ O ₂ Cl ₂ (%):

C 66.79; H 7.21; N 5.56;

ger. (%):

C 66.72; H 7.12; N 5.51.

Example 6

Preparation of N- (3,3-Diphenylpropyl) -N'-3,4-dimethoxybenzyl) -piperazine dihydrochloride

2.8 g of N-3,3-diphenylpropylpiperazine (0.01 mol) and 1.87 g (0.01 mol) of 3,4-dimethoxybenzyl chloride were dissolved in 20 ml of methyl ethyl ketone and the resulting solution was heated at reflux temperature for 7.5 hours . After the reaction liquid was cooled, dry hydrogen chloride gas was passed through the liquid while cooling the liquid to precipitate N- (3,3-diphenylpropyl) -N '- (3,4-dimethoxybenzyl) piperazine dihydrochloride. The crystals of this salt were recrystallized from an ethanol / ether mixed solvent to obtain 4.4 g (87.4% yield) of pure crystals with a melting point of 184 ° C.
Elemental analysis:

Ber. as C ₂₁₁ H JbN ₂ O ₂ Cl ₂ (%):

C 66.79; H 7.21: N 5.56:

found (%):

C 66.81; H 7.23: N 5.53.

Example 7

Preparation of N- (3,3-Diphenylpropyl) -N '- (3.4-dimethoxybenzyl) -piperazine dihydrochloride

2.36 g of N-3,4-dimethoxybenzylpiperazine (0.01 mole) 2.3 g (0.01 mole) of 3,3-diphenylpropyl chloride, 2.5 g (0.011 mol) triamylamine and 2 ml quinoline were in a mixed solvent of 5 ml of cyclohexane and 10 ml of ethyl acetate and the resulting solution at Heated to reflux temperature for 2.5 hours. After cooling, the reaction liquid was filtered with water washed and dried; then dry hydrogen chloride gas was passed through this liquid Cooling of the liquid passed to N- (3,3-diphenyl-

propyl) N '- (3.4-dimethoxybenzyl) piperazine dihydrochloride. The crystals of this salt were recrystallized from a mixed solvent of ethanol and ether to obtain 4.3 g (85.4% yield) of pure crystals with a melting point of 184 ° C.
Elemental analysis:

Ber. as C ₂₈ HJ ₆ N ₂ O ₂ Cl ₂ (%):

C 66.79: H 7.21: N 5.56:

found (%):

C 66.68: H 7.25: N 5.62.

Example 8

Preparation of N- (3.3-Diphenylpropyl) -N '- (3.4-dimethoxybenzyl) -piperazine and organic acid salts thereof

2.8 g of N-3.3-diphenylpropylpiperazine (0.01 mol), 1.87 ε (0.01 mol) of 3,4-dimethoxybenzyl chloride, 0.5 g (0.005 mol) of ethylamine, 1.4 g (0.01 mol) of potassium carbonate and 2 ml Dimethylformamide was mixed with 20 ml of toluene and the resulting mixture was heated at reflux temperature for 2 hours. The reaction liquid was cooled, washed with water by shaking, and the organic liquid layer was concentrated under reduced pressure to obtain 3.6 g (83.6% yield) of the oily N- (3,5-diphenylpropyl) -N '- (3,4-dimethoxybenzyl) -piperazine.
Elemental analysis:

Ber. as C ₂₈ HJ ₄ N ₂ O ₂ (%):

C 78.10; H 7.96: N 6.51:

found (%):

C 78.21: H 7.99; N 6.65.

The above-mentioned oily substance in an amount of 0.86 g (0.002 mol) was dissolved in methanol, and a methanol solution of 0.93 g (0.0044 mol) of citrus acid monohydrate was added. The resulting solution was concentrated, allowed to cool; N- (3,3-Diphenylpropyl) -N '- (3,4-dimethoxybericyl) -piperazine citrate precipitated. The crystals were washed with ether to obtain pure give 1.52 g (93.3% yield) of crystals with mp. 98-104 ⁰ C.

ίο elemental analysis:

C 58.96; H 6.18; N 3.44;

found (o / o):

C 59.24; H 6.29; N 3.60.

The above-mentioned oily substance was dissolved in ether in an amount of 0.86 g (0.002 mol), and a methanol-ether solution of 0.51 g (0.0044 mol) of fumaric acid was added; 1.25 g (94.3% yield) of N- (3,3-diphenylpropy!) - N '- (3,4-dimethoxybenzyl) piperazine difumarate with a melting point of 214-215 ° C. were obtained.
Elemental analysis:

Calculated as C ₃₆ H ₄₂ N ₂ O ₁₀ (%):
C 65.24; H 6.39; N 4.23:
found (%):
C 65.34; H 6.40: N 4.08.

Example 9

Preparation of N- (3,3-DiphenyIpropyl) -N '- (2,3,4-tnmethoxybenzyl) -piperazine dihydrochloride

13.3 g of N-2.3.4-trimethoxybenzylpiperazine (0.05 mol), 11.5 g (0.05 mol) of 3,3-diphenylpropyl chloride. 15 ml of dimethylformamide and 50 ml of toluene were mixed and the resulting mixture was heated at reflux temperature for 4.5 hours. Then, while cooling the liquid, dry hydrogen chloride gas was passed through this reaction liquid to remove crystals of N- (3,3-diphenylpropyl) -N '- (2.3 , 4-trimethoxybenzyl) piperazine dihydrochloride, which was recrystallized from isopropanol to obtain 24.4 g of pure crystals (88.5% yield), melting point 204-205 ° C
Elemental analysis:
Ber. as C ₂₉ H ₃₈ N ₂ O ₃ Cl ₂ · H ₂ O (%):

C 63.15; H 7.31; N 5.08;

found (%):

C 62.85; H 7.52; N 5.34.

Example 10

Preparation of N- (3,3-Diphenylpropyl) -4- (2,3,4-tnmethoxybenzyl) -piperazine

1.4 g of N-3,3-diphenylpropylpiperazine (0.005 mol). 1.1 g (0.005 mol) of 2 ^, 4-trimethoxybenzyl chloride and 0.93 g (0.005 mol) of tributylamine were dissolved in 10 ml of ethylene glycol diethyl ether and the resulting solution was heated at reflux temperature for 2.5 hours. The reaction liquid was cooled and filtered. Concentration of the filtrate under reduced pressure gave 2.1 g of oily N- (33-diphenylpropyl) -N '- (23.4-trimethoxybenzyl) piperazine (91.2% yield).
Elemental analysis:
Calculated as C ₂ 9H3bN ₂ O ₃ (%):
C 75.62; H 7.88; N 6.08:
found (%):
C 75.55; H 7.84; N 6.11.

Example 11

Production of organic acid salts of

. N- (3,3-Diphenylpropyl) -N '- (2,3,4-trimethoxybenzyl) -

piperazins

6 g (0.011 mol) of N- (3 _I 3-diphenylpropyl) -N '- (2,3,4-trimethoxybenzyl) -piperazine dihydrochloride were dissolved in ml of water and treated with 20 ml of a 10 per cent. Sodium hydroxide solution added. The resulting solution was then extracted three times with 10 ml of ether each time, the ether layers were combined, washed with water and concentrated to a total volume of ml. By adding a methanol-ether solution of 2.7 g (0.015 mol) of citric acid monohydrate to 5 ml of this concentrated solution, 4.4 g (92.7% yield) of N- (3,3-diphenylpropyl) -N '- ( 2,3,4-trimethoxybenzyl) piperazine dicitrate monohydrate with a melting point of 86-92 ° C. Elemental analysis:

Ber.ahC ₄ iH ₅₂ N ₂ Oi7 · H ₂ O (%):

C 57.07: H 6.31: N 3.25;

found (%):

C 57.29; H 6.31; N 3.52.

By adding a methanol-ether solution of 1.75 g (0.015 mol) of fumaric acid to 5 ml of the above concentrated ether solution described were 3.6 g (92.1% yield) N- (3.3-Diphenylpropyl) -N '- (2,3,4-trimethoxybenzyl) -piperazine-difumaratmonohy- obtained with a melting point of 196-197 ° C. Elemental analysis:

BeHaIsC ₃₇ H ₄₄ N ₂ O ₁₁ · H ₂ O (%):

C 62.52; H 6.52: N 3.94;

found (%):

C 62.46; H 6.36; N 4.22.

Example 12

Preparation of N- (3,3-Diphenylpropyl) -N '- (3.4,5-trimethoxybenzyl) -piperazine dihydrochloride

2.8 g of N-3,3-diphenylpropylpiperazine (0.01 mol) and 2.2 g (0.01 mol) of 3,4,5-trimethoxybenzyl chloride were dissolved in 20 ml of toluene and heated at reflux temperature for 4.5 hours. After the reaction liquid was cooled, dry hydrogen chloride gas was flowed through the reaction liquid while cooling to precipitate crystals of N- (3,3-diphenylpropyl) -N '- (3,4,5-trimethoxybenzyl) piperazine dihydrochloride. which were recrystallized from an ethanol / ether mixed solvent to obtain 4.3 g of pure crystals (80.6% yield) having a mp of 178 ° C.
Elemental analysis:

Ber. as C ₂₉ H ₃₈ N ₂ O ₃ Cl ₂ (%):

C 65.28: H 7.18; N 5.25;

found (o / o):

C 65.45; H 7.32; N 5.25

Example 13

Preparation of N- (33-Diphenylpropyl) -N '- (3,4 ^ -trimethoxybenzyl) -piperazine dihydrochloride "

2.8 g of N-3,3-diphenylpropylpiperazm (0.01 mol), 2.61 g (0.01 mol) of 3,4,5-trimethoxybenzyl bromide and 1.72 g (0.012 mol) of tripropylamine were dissolved in a mixed solvent 10 ml of acetone and 15 ml of toluene were dissolved and the sublime solution was heated at reflux temperature for 1 hour. - (3,4,5-trimethoxybenzyl) -piperazine-dihydrocnylbria 'to be precipitated. The crystals of this salt were removed from a mixed solvent of chloroform ^! -> Ethylene crystallized to obtain 4.85 g (91.1% yield) of 'pure' crystals with a mp of 178 ° C. ■ .s ■>'' ■ * · Elemental analysis:
ίο Ber. as C ₂₉ H ₃₈ N ₂ O ₃ C1 ₂ (%):

C 65.28; H 7.18: N 5.25;

found (%):

C 65.32; H 7.12; N 5.30.

Example 14

Preparation of N- (3,3-Diphenylpropyl) -N '- (3,4,5-trimethoxybenzyl) -piperazine dihydrochloride

2.66 g of N-3,4,5-trimethoxybenzylpiperazine (0.01 mol), 2.3 g (0.01 mol) of 3,3-diphenylpropyl chloride, 3 ml of dimethylformamide, 1.7 g (0.012MoI) potassium carbonate and 0.1 g sodium iodide were mixed with 20 ml butyl acetate mixed and the resulting mixture heated at reflux temperature for 2 hours. The reaction liquid was filtered after cooling, and the filtrate was concentrated under reduced pressure to give an oily To obtain residue which was extracted by shaking with ether and water; the ether layer was dried and then bubbling dry hydrogen chloride gas through the ethereal solution while cooling this solution

N- (3,3-Diphenylpropyl) -N '- (3,4,5-trimethoxybenzyl) -piperazine dihydrochloride to precipitate its crystals from a mixed solvent of methanol and ether was recrystallized to obtain 4.76 g (89.2% yield) of pure crystals with a melting point of 178 ° C. Elemental analysis:

Ber. as C ₂₉ H ₃₈ N ₂ O ₃ Cl ₂ (%):
C 65.28; H 7.18; N 5.25;
found (%):
C 65.19; H 7.27; N 5.19.

Example 15

Preparation of N- (3,3-Diphenylpropyl) -N '- (3.4,5-trimethoxybenzyl) -piperazine and organic acid salts thereof

2.8 g of N-3,3-diphenylpropylpiperazine (0.01 mol),

2.17 g (0.01 mole) 3,4,5-trimethoxybenzyl chloride, 0.51 g

(0.005 mol) triethylamine and 1.4 g (0.01 mol) potassium

5c carbonate were mixed with 20 ml of toluene and that

obtained mixture at reflux temperature for 2 hours

The reaction liquid was cooled by

Shake washed with water and then the

organic liquid layer under reduced pressure

concentrated around 3.8 g (85% yield) of the oily

N- (33-Diphenylpropyl) -N '- (3,4,5-trimethoxybenzyl) -piperazine.
Elemental analysis:

Ber. as C ₂₉ H ₃₆ N ₂ O ₃ (%):
C 75.62; H 7.88; N 6.08;
found (%):
C 7533; H 7.87: N 6.10.

The above oily substance was used in an amount of

65 0.5 g (0.0011 mol) dissolved in 10 ml of ether, including a 0.5 g

(0.0024 mol) citric acid monohydrate in a

thanoL / ether mixture containing solution was added to 0.94 g (97.0% yield) N- (33-Diphenylpro-

pyl) -N '- (3,4,5-trimethoxybenzyl) -piperazine dicitrate dihydrate with a melting point of 98 ° C. Elemental analysis:

Ber. as C41H52N2O17 2 H ₂ O (%):

C 55.90; H 6.41; N 3.18;

found (%):

C 55.65; H 6.22; N 2.89.

To a methanol solution of 0.5 g (0.0011 mol) of the above-mentioned oily substance, a methanol

solution of 1.29 g (0.0025 mol) of fumaric acid give the resulting solution concentrated and cooled 0.74g (94.9% yield) N- (3 ^ -diphenylprop (3,4,5-trimethoxybenzyl) -piperazine difumarate-mc drat with a melting point of 194-195 ° C Elemental analysis:

BeHaIsC ₃₇ H ₄₄ N ₂ O _n ■ H ₂ O (%):

C 62.52; H 6.52; N 3.94;

found (%):

C 62.35; H 6.40; N 3.98.

Claims (3)

Claims: 1. N- {3,3-DiphenyIpropyl) -N'-benzylpiperazines of the general formula ^ CHCH ₂ CH ₂ - N ^^ N - CH, - ^^ in which η represents an integer from 0 to 3, and salts thereof. 2. N- (3,3-Diphenylpropyl) -N'-benzylpiperazine
and its salts. 3.N- (3,3-Diphenylpropyl) -N '- (3,4-dimethoxy- (OCH ₃ J _{N 3} J