NO123719B - - Google Patents

Description

Procedure for the production of new, therapeutic

active phenylcyclopropane derivs.

The present invention relates to the production of new therapeutically active phenylcyclopropane derivatives.

The new compounds produced according to the invention can be expressed by the following general formula:

where

means a straight or branched alkyl radical with 2-8. carbon atoms or a benzyl radical, and

R2 represents a hydrogen atom or a straight or branched alkyl radical with 1-8 carbon atoms, or

R 1 and R 2 together with the nitrogen atom mean a morpholine, piperidine or pyrrolidine ring.

The compounds which. produced according to the invention, can be present as cis- or trans-isomers. The invention includes production of the separate cis and trans isomers as well as the cis-trans mixtures thereof. At the moment, the trans isomers seem to have a particularly beneficial effect and are therefore preferred.

The new compounds can be prepared by various methods which are able to give the desired derivatives in good yield. In a preferred method, the compounds of formula I are prepared by the following synthesis:

where X is halogen, n is 0 or 1 and R 1 and R 2 are as indicated above.

This reaction is preferably carried out by adding the acid chloride to the amine or to the amine hydrochloride at a temperature from 0°C to 50°C and in the presence of an acid-binding agent, such as an excess of the amine or such as pyridine, a trialkylamine, an N,N-dialkylaniline or an alkali metal or alkaline earth metal carbonate or bicarbonate. The acid chloride and/or amine can be dissolved in a suitable solvent, such as ethyl ether, acetone, benzene or a mixture thereof.

Alternatively, the acid chloride can be added to a concentrated aqueous solution of the amine. After the reactants are. brought together, the reaction is completed by stirring the reaction mixture at a temperature from 20 to 120°C, preferably at room temperature, in the course of e.g. from 15 minutes to 11 hours.

By another method, compounds of formula I are prepared, where

R2 is hydrogen and R-^ is as indicated above, in the following reaction:

where Y is a lower alkyl radical with from 1 to 5 carbon atoms.

This reaction is best carried out by heating the reactants in the presence of a polar solvent, such as water or a lower alkanol, in a closed vessel at a temperature of 130 to 180°C.

The new phenylcyclopropane derivatives produced according to the present invention exhibit important pharmacological properties and relatively low toxicity.

The new compounds produced according to the invention can be given orally, subcutaneously or intravenously in any of the known pharmaceutical forms that are usually used for these administrations.

The only previous publication relating to compounds "similar" to the phenylcyclopropanamide derivatives produced by the present process is J. Med. Pharm. Soc._5_, 12I+-3-1281+. According to this article, it is assumed that phenylcyclopropane derivatives can be attributed to an antidepressant activity that unfolds via an MAO-inhibiting activity.

One. range of phenylcyclopropane derivatives have been investigated, and

among these were

the only amide compound.

This compound was found to be essentially completely devoid of MAO inhibitory activity and was therefore later scrapped.

However, it has surprisingly been shown that the phenylcyclopropanamide derivatives produced by the present method exhibit an anti-spasmodic activity and/or a depressant effect on the central nervous system.

The depressant effect on the central nervous system caused by the compounds produced by the present method has been able to be determined both by a direct examination of the effect on animals treated with ten new phenylcyclopropanamide derivatives and indirectly by examining the changes in the effect of known pharmaceutical products caused by these compounds.

The direct sedative effects are clearly shown in rats after oral administration of various compounds, especially the disubstituted compounds, in doses varying from 20 to 80 mg/kg.

Depending on the dose received, the animals first appear to be uninterested in their surroundings, and they react only weakly to stimuli. Then there is an uncoordinated muscle movement and paralysis.

The indirectly achieved results were demonstrated by the fact that

a) certain monosubstituted derivatives, such as e.g. the compounds where R2=Hog and R1=C2H5, or CHCCH^, are capable of producing an antagonistic effect against convulsions induced by the administration of tetrahydro-6,7,8,9-azepo-5-tetrazole. b) A number of the mono- or disubstituted compounds effect a prolongation of lethargy caused by the administration of a

barbiturate preparation.

In this case, the monosubstituted derivatives have also shown to be particularly active. Among the disubstituted derivatives, a potentially important effect occurred in the compounds where R-^=R2, C2H^ or CH2CH(CH^)CH^ and where NR-jR^ is pyrrolidine.

c) The disubstituted compounds, with the exception of compounds where NR-|R2= pyrrolidine or piperidine, are able to form a

strong antagonistic action against locomotor stimulation induced by parenteral administration of phenyl-1-amino-2-propane.

An investigation of the possible spasmolytic properties of the compounds was carried out with the isolated intestine of guinea pigs that had been stimulated with acetylcholine and barium chloride, showing that the disubstituted compounds had the same type of spasmolytic properties as papaverine, but far stronger.

These properties increase progressively for compounds where R-^=R2=C2H^ and C-^H^ and have a strength comparable to papaverine for compounds where R-L=R2=CH(CH^)2, C^H^ , CH(CH^)CH2CH^ and CH^CHCCH-^CHy They decrease for compounds where NR-^R^piperidine, pyrrolidine and morpholine.

It is also noteworthy that the activity has been established by experiments carried out "in vivo" in connection with rats by determining the effect on the intestinal peristaltic activity stimulated by treatment with a parasympathomimetic preparation.

It has been determined by oral administration and examination of rats that unit doses of 50-100 mg/kg of the compounds produced by the present method are always well tolerated.

Daily oral administration of a dose of 25 mg/kg, which was continued for h weeks, did not lead to any change in the weight gain curve or in the hemocracy. Histological examinations, carried out at the end of this period, of the main parenchymal organs gave completely negative results.

The results that have been obtained in connection with humans are comparable to the results that have been obtained in connection with animals.

In particular, trans-N,N-di-.sec.butylphenyl-2-cyclopropanamide in a dose of 25 mg proved particularly indicated for the treatment of convulsive conditions in smooth muscles.

This treatment did not cause any side effects that were worth it

note.

Some examples shall be given to illustrate the invention in more detail: Example 1

Trans-N-ethyl-2-phenylcyclopropanecarbonamide

30 g (0.166: mole) of trans-2-phenylcyclopropanecarbonyl chloride (J.A.C.S., 70, 2200) was added dropwise with stirring to 5<*>+ g (0.838 mole) of 7-0. $-Ig aqueous ethylamine. During this addition, the temperature of the reaction mixture was kept below 10°C. After the addition was finished, the mixture was stirred for 1 hour and allowed to warm to room temperature. The mixture was then poured into 200 ml of water. The precipitate was collected by filtration, washed with water until the wash water gave no reaction to chloride ion and dried at 50°C in vacuum. Yield: 2%1 g (92.5 a-v the theoretical). The product was purified by crystallization from ethyl acetate. Melting point: 105 - 106°C.

Analysis: Calculated for C^Hj^NO:

C 76.15; H 7.99; N 7.^0;

warm: C 75.96; II 7.99; N 7,<1>+0.

Example 2

Cis-N-ethyl-2-phenyleylcyclopropanecarbonamide

Cis-2-phenylcyclopropanecarbonyl chloride was dissolved in 100 ml of anhydrous ethyl ether - and added dropwise with stirring to a solution of 28 g -(0v610 moi) ethylamine in 250 ml of anhydrous ethyl ether. During this addition, the temperature of the reaction mixture was kept below 10°C. After the addition was complete, the mixture was stirred for 1 hour and allowed to warm to room temperature. After standing overnight, the precipitate was removed by filtration and washed with ethyl ether. The combined filtrate and washings were treated with 100 ml of 0.1 W sodium hydroxide, washed with water until the wash water gave no reaction with chloride ion, dried over "Drierite", filtered and decolorized with carbon black. Evaporation of the solvent left a solid product which was purified by crystallization from isopropyl ether. Melting point 61 - 62°C.

The cis-2-phenylcyclopropanecarbonyl chloride was prepared by adding 59.^ g (0.<1>+99 mol) thionyl chloride in 160' ml of petroleum ether dropwise with stirring to a suspension of ho g (0.2^-6 mol) cis -2-phenylcyclopropanecarboxylic acid in 160 ml of petroleum ether kept below 15°C. After the addition was complete, the mixture was stirred for 1 hour and allowed to warm to room temperature. Removal of the petroleum ether under reduced pressure left an orange-colored oily cis-2-phenylcyclopropane carbonyl chloride. (This preparation is slightly different from that described by J. Smejkal and J. Farkas Coll. Czech. Chem. Comm, 28,<1>+8<*>4-, 1963.)

Example 3

Trans-JJ-(n-propyl)-2-phenylcyclopropanecarbonamide

A mixture of 19.1 g (0.1 mol) trans-ethyl-2-phenylcyclopropane carboxylate (J.A.C.S., 70, 2199-2200), 12 g (about 0.2 mol) n-propylamine and 20 ml of ethyl alcohol was heated at 150°C in a closed rudder. After approx. After 10 hours, the ethyl alcohol was removed from the reaction mixture by distillation under reduced pressure. The residue was dried at 50°C in vacuo and crystallized from naphtha. The product was purified by recrystallization from ethyl acetate. Melting point 123 - I2<l>+°C.

Analysis: Calculated for C^H-^NO:

C 76.8l; H 8.1+3-, N 6.89;

Found: ■ C 77.09; H 8.38; N 6.89.

Example 1+

Trans-N-isopropyl-2-phenylcyclopropanecarbonamide

The procedure in example 1 was repeated by reacting <1>+0 g (0.222 mol) of trans-2-phenylcyclopropanecarbonyl chloride with 50 g (0.88 mol) of 50% isopropylamine. The product was purified by crystallization from ethyl acetate. Melting point 151 - 159°C.

Analysis:. Calculated for C^H-^NO:

C 76.81; H 8,<1>+3; N 6.89;

Found: C 76.28; H 8.38; N 6.9^.

Example 5

Trans-N-(n-butyl)-2-phenylcyclopropanecarbonamide

15 g (0.083 mol) of trans-2-phenylcyclopropanecarbonyl chloride was added dropwise with stirring to a mixture of 9.6 g (0.087 mol) of n-butyrylamine hydrochloride and 10 ml of pyridine. During this addition, the reaction mixture was kept below 10°C. After the addition was finished, the mixture was stirred for 3 hours and allowed to warm to room temperature. The mixture was allowed to stand overnight, and the excess pyridine was distilled off under reduced pressure. The residue was washed with water until the wash water gave no reaction to chloride ion, and dried at 50°C in vacuum. The yield was 15 g (83.5% of the theoretical). The product was purified by crystallization from ethyl acetate. Melting point 108-109°C.

Analysis: Calculated for C^H^NO:

C 77.38; H 8.18; N 6, hh;

Found.: C 76 .98; H 8 .80.; N 6 , h0

Example 6

Trans-N-isobuty1-2-phenylcyclopropanecarbonamide

20 g (0.111 mol) of trans-2-phenylcyclopropahcarbonyl chloride was added dropwise with stirring to a solution of 8.5 g (0.116 mol) of isobutylamine and 18 g of anhydrous pyridine. During this addition, the temperature of the reaction mixture was kept below ■5°C. After the addition was finished, the mixture was heated to approx. 80°C and stirred for 15 minutes. The solution was allowed to cool slowly to room temperature, with stirring, and was then poured into 100 ml of water. The precipitate was collected by filtration, washed with water until the wash water gave no reaction to chloride ion, and dried at 60°C

in vacuum. The yield was 21.5 g (89% of the theoretical). The product was purified by crystallization from a solvent mixture of ethyl alcohol and water.. Melting point 112-113°C..

Analysis: Calculated for C-^H-^NO:

c 77^36; H 8.88; N -6.¥+;

Found: C 77.33; H 8.89; N 6.50..

Example 7

. trans- N- sec. outyl-2-phenylcyclopropanecarbonamide

A solution of 10 g (0.0555 mol) trans-2-phenylcyclopropane carbonyl chloride in 50 ml anhydrous acetone was added dropwise with stirring to a solution of 5.1 g (0.056 mol) sec-butylamine and 5.6 g (0.0555 mol) anhydrous triethylamine in 50 ml anhydrous acetone. During this addition, the temperature of the reaction mixture was kept below 10°C. After the addition was complete, the mixture was stirred for 2 hours and allowed to warm to room temperature. The precipitate was removed by filtration and washed with acetone. The combined filtrate and washings were washed with water until the washings gave no reaction to chloride ion. The solvent was removed and the residue was dissolved in 100 ml of benzene. After washing with 0.1 N sodium hydroxide and water, the solution was decolorized with carbon black, concentrated to h-0 ml by boiling and allowed to cool. The precipitate was collected by filtration. The yield was<*>+.2 g (35% of the theoretical). The product was purified by crystallization from benzene. Melting point 133-13<1>+<0>C. Analysis: Calculated for C-^H-^NO: C 77.38; H 8.81; N 6.56;.

Found: C 77.58; H 8.60; N 6.53.

Example 8

trans-N- tert. buty1-2-phenylcyclopropanecarbonamide

A solution of 10 g (0.0555 mol) of trans-2-phenylcyclopropane carbonyl chloride in 50 ml of anhydrous benzene was added dropwise with stirring to a solution of 4.1 g (0.056 mol) of tert-butylamine and 5.6 g (0.0555 mol) of anhydrous triethylamine in 50 ml of anhydrous benzene. During this addition, the temperature of the reaction mixture was kept below 10°C. After the addition was complete, the mixture was stirred for 2 hours and allowed to warm to room temperature. The precipitate was removed by filtration and washed with benzene. The combined filtrate and washing liquid were washed with water until the washing water gave no reaction to chloride ion. The solvent was removed by distillation first at atmospheric pressure and then under reduced pressure. The yield was 7 g (58% of the theoretical). The product was purified

by crystallization from isopropyl ether. Melting point 136-138°C. Analysis: Calculated for C^H^NO: C 77.38; H 8.81; N 6.1+5; '

Found: C 77.93; H 8.57; N 6.51.

Example 9

trans-N-(n-amyl)-2-phenylcyclopropanecarbonamide

The procedure in example 6 was repeated by reacting 15 g (0.083 mol) of trans-2-phenylcyclopropanecarbonyl chloride with a mixture of 7.3 g (0.083 mol) of n-amylamine and 13 g of anhydrous pyridine. The yield was 17.5 g (91% of the theoretical). The product was purified by

crystallization from ethyl acetate. Melting point 95 96 C.

Analysis: Calculated for C^EL-^NO:

C 77.88-, H 9.15; N 6.05;

Found: C 77.60; H 9.26; N 6.01.

' Example 10

trans-N,N-diethy1-2-phenylcyclopropanecarbonamide

A solution of 15 g (0.083 mol) of trans-2-phenylcyclopropane carbonyl chloride in 15 ml of anhydrous benzene was added dropwise with stirring to a solution of 15.2 g (0.207 mol) of diethylamine in 200 ml of anhydrous benzene. During this addition, the temperature of the reaction mixture was kept below 30°C. After the addition was finished, the mixture was stirred for 1 hour at room temperature. The precipitate was removed by filtration. The filtrate was washed with high-% aqueous hydrochloric acid and then with water until the wash water gave no reaction to chloride ion. The benzene was removed by distillation under reduced pressure. The oily residue was subjected to fractional distillation, and the fraction boiling at 129-131°C at 0.5 mm Hg was collected. The yield was 13.5 g (75% of the theoretical). d<20>°=1.0308; n<20>°=1.5386.

20° D Analysis: Calculated for C-^H-^NO: C 77.38; H 8.81; N 6.45;

Found: .C 77.3"+; H 8.82; N 6.44.

Example 11

cis-N,N-diethyl-2-phenylcyclopropanecarbonamide

The procedure in example 10 was repeated by reacting a solution of 44 g (0.246 g) of cis-2-phenylcyclopropanecarbonyl chloride.

(prepared by the method in example 2) in 100 ml of anhydrous ethyl ether with a solution of 54 g (0.738 mol) of diethylamine in 200

ml anhydrous ethyl ether. The product was purified by crystallization from isopropyl ether. Melting point 58 - 59°C.

Analysis: Calculated for C-^H^NO:

C 77.385H 8.81; N 6.45;

Found: C 77.48; H 8.86; N 6.60.

Example 12

trans-N.N-(di-n-propyl)-2-phenylcyclopropanecarbonamide

The procedure in Example 10 was repeated by reacting a solution of 15 g (0.083 mol) trans-2-phenylcyclopropanecarbonyl-

chloride in 10 ml of anhydrous benzene with a solution of 21 g (0.207 mol) of di-n-propylamine in 200 ml of anhydrous benzene. The yield was 15 g (86%

of the theoretical). Boiling point 137 - 139°C at 0.5 mm Hg.

?,o ?1o

d^<1>= 1.006; n1 = 1.5288

20° D

Analysis: Calculated for C-^^^NO:

C 76.32; H 9.45; N 5.71;

Found: C 77.25"; H 9.3'2; N 5.66.

Example 1?

trans- N. N- di- isopropy1- 2- phenylcyclopropanecarbonamide

A solution of 15 g (0.083 mol) trans-2-phenylcyclopropane carbonyl chloride in 30 ml anhydrous ethyl ether was added dropwise with stirring to a solution of 18.5 g (0.182 mol) di-isopropylamine in 70 ml anhydrous ethyl ether . During this addition, the temperature of the reaction mixture was kept below 10°C. After this addition was complete, the mixture was stirred for 1 hour and allowed to warm to room temperature. The precipitate was removed by filtration and washed with ethyl ether. The combined filtrate and washings were washed with water, with 0.1 N hydrochloric acid and again with water until the washings gave no chloride ion reaction. The solvent was removed by evaporation, the oily residue was subjected to fractional distillation and the fraction boiling at 115-118°C at 0.-2-0.3 mm Hg was collected. The yield was 12.3 g (63.7% of the theoretical).

d20° .1.0055; n 20°- 1.53325

20° D

Analysis: Calculated for C-^B^NO:

C 78.32; H 9.45; N 5.71;

Found: C 76.86; H 9.44; N 5.85.

Example 14

trans-N,N-(dl-n-butyl)-2-phenylcyclopropanecarbonamide

A solution of 15 g (0.083 mol) of 2-phenylcyclopropanecarbonyl chloride in 15 ml of acetone was added dropwise with stirring to a solution of 14 g (0.084 mol) of di-n-butylamine hydrochloride in 19.7 g of anhydrous pyridine. During this addition, the temperature of the reaction mixture was kept below 5°C. After the addition was complete, the mixture was stirred for 11 hours and allowed to warm to room temperature. After standing overnight, the precipitate was removed by filtration and washed three times with 30 ml portions of ethyl ether. The combined filtrate and washings were evaporated under reduced pressure. The residue was dissolved in anhydrous ethyl ether and washed twice with 50 ml portions of 1N sodium hydroxide and then with 1N hydrochloric acid. The solution was washed with water until the wash water gave no reaction to chloride ion, and evaporated under reduced pressure. The oily residue was dissolved in anhydrous benzene and fractionated. The yield was 13 g ^ 57% of the theoretical). Boiling point was 137-140°C at 0.4 mm Hg, n<20>= -1.8185.

Analysis: Calculated for C-^gH^NO:

C 79.07; H 9.96; N 5.12;

Found: C 79.06; H 9.96; N 5.10.

Example 15

trans-N,N-di-isobuty1-2-phenylcyclopropanecarbonamide

A solution of 10 g (0.0555 mol) of 2-phenylcyclopropanecarbonyl chloride in 50 ml of anhydrous ethyl ether was added dropwise with stirring to a solution of 7.2 g (0.0557 mol) of diisobutylamine and 5.65 g of triethylamine in 50 ml anhydrous ethyl ether. During this addition, the temperature was kept below 10°C. After the addition was complete, the mixture was stirred for 2 hours and allowed to warm to room temperature. The precipitate was removed by filtration and washed with ethyl ether. The combined filtrate and ether washes were washed first with 0.1 N hydrochloric acid and then with water until the wash water gave no reaction to chloride ion. The product was recovered by evaporation of the solvent under reduced pressure. The yield was 13.8 g (91% of the theoretical). The product was purified by crystallization

sation from isopropyl alcohol. Melting point 54 - 55°C.

Analysis: Calculated for C-^gH^^NO:

c 79.07-, H 9.95; N 5,12.5

Found: C 79.12; H 9.78; N 5.16.

Example 16

trans-N.N-(di-sec-butyl)-2-phenylcyclopropanecarbonamide

The procedure in Example 10 was repeated by reacting a solution of 15 g (0.083 mol) of trans-2-phenylcyclopropanecarbonyl chloride in 20 ml of anhydrous benzene with a solution of 23 g (0.171 mol) of di-sec-butylamine in 100 ml of anhydrous benzene . The yield was 22.2 g ■

(98% of the theoretical). Boiling point 13*4- - 136°C at 0.5 mm Hg:

d<l8>° = 0.9942.; n<l8>°=1.5244. 20° D Analysis: Calculated for C-^gH-^NO: C 79.075H 9.95.; N 5.12;

Found: C 79.54; H 9.93; N 5.10.

Example 17

trans-N.N-(di-n-amyl)-2-phenylcyclopropanecarbonamide

30 g (0.166 mol) of trans-2-phenylcyclopropanecarbonyl chloride was added dropwise with stirring to a solution of 26.5 g (0.168 mol) of di-n-amylamine in 27 g of anhydrous pyridine. During this addition, the temperature of the reaction mixture was kept below 50°C. After the addition was complete, the mixture was stirred for 1 hour at 50°C. The pyridine was removed by evaporation, and the oily residue was added to 100 ml of water. The oily layer was washed with 100 ml of 3% hydrochloric acid and with water until the wash water gave no reaction to chloride ion, and was then subjected to fractional distillation. Boiling point 155 - 16-0°C at 0.5 mm Hg; yield 27.9 g

(55.5% of the theoretical)..

d<20>°= 0.9660; N<20>°= 1.5148

20° D Analysis: Calculated for (^qH-^NO: C 79.68; H 10.36; N 4.65;

Found: C 79.20; H 10.26-, N 4.52.

Example 18

N-(trans-2-phenylcyclopropanecarbonyl)-morpholine

A solution of 10 g (0.0555 mol) of 2-phenylcyclopropanecarbonyl chloride in 25 ml of acetone and 25 ml of ethyl ether was added dropwise with stirring to a solution of 5.1 g of morpholine and 5.65 g of triethylamine in 25 ml of acetone and 25 ml of ethyl ether. During this addition, the temperature was kept below 10°C. After the addition was complete, the mixture was stirred for 2 hours and allowed to warm to room temperature. The precipitate was removed by filtration and washed with a solvent mixture of acetone and ethyl ether. The combined filtrate and washings were evaporated under reduced pressure. The oily residue was treated with 0.1 N hydrochloric acid and then solidified. The solid material was collected by filtration, washed with water until the wash water gave no reaction to chloride ion and dried in vacuo at 50°C. The yield was 10.4 g (81% of the theoretical). The product was purified by crystallization from isopropyl ether. Melting point 72 - 73°C.

Analysis: Calculated for C-^H-^f^:

C 72.70; H 7.4l; N 6.06;

Found: C 72.63; H 7.4-9; N 6.10.

Example 19

N-(trans-2-phenylcyclopropanecarbonyl)-pyrrolidine

The procedure in example 10 was repeated by reacting a solution of 30 g (0.166 mol) of trans-2-phenylcyclopropanecarbonyl chloride in 40 ml of anhydrous benzene with a solution of 25 g (0.348 mol) of pyrrolidine. The yield was 34 g (95% of the theoretical). The product was purified by crystallization from ethyl acetate. Melting point 102-5 - 103°C

Analysis: Calculated for C-^H-^NO:

C 78.11; H 7.96; N 6.5l;

Found: C 78.30; H 7.90; N 6.49.

Example 20

N-(trans-2-phenylcyclopropanecarbonyl)-piperidine

A solution of 10 g (0.0555 mol) of trans-2-phenylcyclopropane carbonyl chloride in 30 ml of ethyl ether was added dropwise with stirring to a solution of 9.9 g (0.116 mol) of piperidine in 70 ml of anhydrous ethyl ether. During this addition, the temperature of the reaction mixture was kept below 10°C. After the addition was complete, the mixture was stirred for 1 hour and allowed to warm to room temperature. The precipitate was removed by filtration and washed with ethyl ether. The combined filtrate and the washing liquids were washed first with 0.1 N hydrochloric acid and then with water until the washing water gave no reaction to chloride ion. After the solution had been dried over "Drierite", the solvent was removed by distillation, first at atmospheric pressure and then under reduced pressure. The yield was 12.1 g (95% of the theoretical). The product was purified by crystallization from isopropyl alcohol. Melting point 90 - 91°C. Analysis: Calculated for C-^H-^NO: C 78.56; H 8.35; N 6.11;

Found: C 78.51; H 8,<1>+3; N 6.10.

Example 21

trans-(N-ethyl-N-benzyl)-2-phenylcyclopropanecarbonamide

The procedure in example 18 was repeated by conversion of

20 g (0.111 mol) of trans-2-phenylcyclopropanecarbonyl chloride in 50 ml of anhydrous ethyl ether, a solution of 15.8 g (0.117 mol) of ethyl benzylamine and 11.3 g (0.111 mol) of triethylamine in 150 ml of anhydrous ethyl ether. The yield was 26.5 g (86% of the theoretical). Boiling point 155 - 160°C at 0.2 mm Hg.

Analysis: Calculated for C-^^jNO:

C 81.68; H 7.58; N 5.01;

Found: C 81.26; H 7.66; N 5.01.

Claims (1)

Procedure for the production of new, therapeutically active compounds with the formula: where means a straight or branched alkyl radical with 2-8 carbon atoms or a benzyl radical, and R2 means a hydrogen atom or a straight or branched alkyl radical with 1-8 carbon atoms, or R-j^ and R2 together with the nitrogen atom mean a morpholine, piperidine or pyrrolidine ring, characterized in that a) a compound with the formula where X represents a halogen atom, is reacted with an amine of the formula NHR-^R2, where R^ and R2 have the same meanings as stated above, or with a hydrohalide of the amine, orb) a compound of the formula where Y means an alkyl radical with 1-5 carbon atoms, is reacted with an amine of the formula H2NR-^, where R-^ has the same meaning as above.