GB1570209A

GB1570209A - Secondary and teriary 2 - (2 - furyl)-ethylamines

Info

Publication number: GB1570209A
Application number: GB53734/76A
Authority: GB
Original assignee: Chinoin Gyogyszer es Vegyeszeti Termekek Gyara Zrt
Current assignee: Chinoin Private Co Ltd
Priority date: 1975-12-29
Filing date: 1976-12-23
Publication date: 1980-06-25
Also published as: AR217703A1; CH633284A5; GR62443B; ATA957376A; SE7614473L; SE429654B; FR2336928B1; SU741796A3; AR221212A1; PL111945B1; CS216166B2; AT361460B; JPS5283359A; IL51145A; PL194802A1; DD131748A1; IL51145A0; DE2658064C2; CS216167B2; YU148982A

Abstract

The novel N-2-(2-furylethyl)amines of the formula I, in which the symbols R<1>, R<2> and R<3> have the meaning given in Claim 1, have an inhibitory effect on the monoamide oxidases without having any unwanted amphetamine effect. They are prepared by reacting a compound of the formula II with a compound of the formula III, in which compounds one of the radicals A or B corresponds to the group <IMAGE> , in which R<2> has the above meaning, while the other represents halogen or a sulphonic acid ester group. <IMAGE>

Description

(54) SECONDARY AND TERTIARY 2-(2-FURYL) ETHYLAMINES (71) We, CHINOIN GYOGYSZER ES VEGYESZETI TERMEKEK GYARA RT., a Hungarian Body Corporate, of 1-5 To-utca, Budapest IV, Hungary, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement:- This invention relates to N - 2 - (furyl) ethylamine derivatives, a process for the preparation thereof and pharmaceutical compositions comprising them.

According to an aspect of the present invention there are provided racemic or optionally active compounds of the formula 1

and acid addition salts thereof (wherein R1 and R2 are hydrogen or C~4-ålkyl, and R3 is C2-haloalkenyl, haloprop-2-enyl or propargyl).

It is known that furyl-ethylamines exhibit a pharmacological effect similar to that of phenyl-ethylamines [J. Pharmacol 72, 265 (1941)]. The new compounds of the formula I are, in at least some cases, substantially free of the undesired "amphetamine" effect, but are capable of selective inhibition of monoamino-oxidase. Some known compounds of different chemical structure have been described as having selective monoaminooxidase inhibiting effects [Biochemical Pharmacology 18, (1969) 1447; Br. J. Pharmacology 45, (1972) 4901. The latter compounds however inhibit mainly the oxidation of 5-hydroxytryptamine. It is known that N, cr- dimethyl - N - A - phenyl - N propynylamine (British Patent No.

1,031,425) inhibits the oxidation of benzylamine [(Br. J. Pharmacology 45, 490 (1972)1. The compounds of the formula I, however, might be considered to have more favourable properties than the phenyl-ethylpropynyl amine derivatives mentioned above.

The compounds of the formula I wherein R' is C,~4-alkyl possess an asymmetric carbon atom and can exist in racemic or in optically active forms. The present invention encompasses both the racemic and optically active forms of the compounds of the formula I and the preparation thereof.

The term "C,~4 alkyl group" relates to straight or branched chain alkyl groups having 1--4 carbon atoms (e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, preferably methyl). The C2-haloalkenyl group and the haloprop-2-ethyl group comprise preferably chlorine or bromine as halogen (e.g. bromo-prop-2-enyl).

The salts of the compounds of the formula I may be formed with inorganic or organic acids (e.g. hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, maleic acid, tartaric acid, fumaric acid, succinic acid, or lactic acid).

According to a further aspect of the present invention there is provided a process for the preparation of compounds of the formula I

which comprises a) reacting a corresponding compound of the formula

with a compound of the formula 111 B-R3 (III) wherein R', R2 and R3 are as stated above and A and B represent groups, which on reacting with each other are capable of forming the bivalent group

and if desired converting a C3-haloalkenyl group at R3 in the product obtained into a prop-2-ynyl group; or b) condensing a compound of the formula IV

with formaldehyde and acetylene to form a compound I in which R3 is propargyl. After these reactions if desired one may then convert a compound of the set formula I thus obtained into its acid addition salt or set free a compound of the formula I from its acid addition salt and/or resolve a racemic compound of the formula I into its optically active isomers.

According to an embodiment of method a) of our process a compound of the formula IV is reacted with a compound of the formula III, wherein R3 is propargyl and B is halogen or a sulfonic acid ester group, e.g.

an alkylsulfonyloxy or arylsulfonyloxy group, such as chlorine, bromine, benzenesulfonyloxy, p-toluenesulfonyloxy or methanesulfonyloxy, to form a compound I in which R3 is propargyl. The reaction may be carried out in a solvent or without solvent. It is preferable to add an acid binding agent to the reaction mixture. As acid binding agent inorganic or organic bases, such as alkali or alkaline earth metal hydroxides, carbonates or tertiary amines may be used. An excess of the amine of the formula IV may serve as acid binding agent too. In this case one may preferably use the excess of amine both as acid binding agent and reaction medium. The reaction may be accomplished preferably at a temperature between 20 and 1200C. As solvent aliphatic and aromatic hydrocarbons, such as petrol ether, benzene and its homologues, alkanols (e.g. ethanol, methanol, butanol, etc.) ketones (e.g. methyl-ethylketone, cyclohexanone, etc. Provided these do not react with the amine) may be used. Most preferably an amine of the formula IV is dissolved in toluene and propargyl bromide and an aqueous sodium hydroxide solution are added simultaneously dropwise. The reaction is completed by heating if necessary.

The product is recovered from the reaction mixture by addition of an alkali and subsequent extraction. if the reaction is carried out in a water-immiscible solvent, it is preferred to remove this solvent by distillation and add aqueous sodium hydroxide to the residue. The two-phase mixture is extracted with a water-immiscible solvent (e.g. ether or benzene), the extract is dried, evaporated and the residue is purified by fractional distillation.

If the compound of the formula I thus obtained is a tertiary base (R2 is alkyl) the product may be advantageously purified by the acylation of the evaporation residue. In this case the unreacted starting material of the formula IV (secondary base) is acylated, the acylated product thus obtained is insoluble in dilute acids and the tertiary base of the formula I can be recovered in pure form by extraction into dilute acid.

Acylation may be carried out with conventional acylating agents (e.g. acid anhydrides or acid chlorides such as acetic anhydride or benzoyl chloride) in the presence of an alkali. After acylation the reaction mixture is extracted with cold diluted hydrochloric acid, whereupon the acidic extract is made alkaline, the precipitated tertiary amine of the formula I is extracted with a solvent, dried, evaporated and the residue is distilled off.

The product may be converted into a salt formed with an organic or inorganic acid.

According to another embodiment of process a) a compound of the formula IV is reacted with propargyl aldehyde with simultaneous or subsequent reduction of the imine formed to yield a compound I in which R3 is propargyl. One may react the compound of the formula IV with propargyl aldehyde in a solvent or without solvent. As reaction medium preferably waterimmiscible solvents (e.g. benzene and its homologues, such as toluene, xylene or petrol ether) may be used. In this case the water formed in the reaction is separated and this shifts the equilibrium towards the formation of the Schiff-base. This product is then reduced into the corresponding compound of the formula I. One may also carry out condensation and reduction simultaneously. Reduction may be preferably accomplished with the aid of nascent hydrogen.

According to a further embodiment of method a) a 2-furyl-acetone of the formula VI

is reacted with an amine of the formula V

with simultaneous or subsequent reduction of the imine formed. The reduction may be accomplished preferably with the aid of nascent hydrogen.

According to a further embodiment of, method a) a compound of the formula VII

(wherein X is halogen or a sulfonic acid ester radical, e.g. an alkylsulfonyloxy or arylsulfonyloxy group, such as chlorine, bromine, methanesulfonyloxy, phenylsulfonyloxy or p-toluenesulfonyloxy) is reacted with an amine of the formula V. For example one may react a 2-furyl-ethyl halide with methylpropynylamine. The reaction may be carried out in the presence or absence of a solvent. As reaction medium hydrocarbons (e.g. benzene and its homologues or petrol ether) alcohols or ketones may be used, or an excess of the amine component may serve as reaction medium. The reaction may be preferably accomplished in the presence of an acid binding agent. For this purpose organic or inorganic bases or an excess of the amine of the formula V may be used. The reaction may be carried out at a temperature between 20 and 130"C. The recovery and purification of the product may be carried out by known physical methods (e.g.

extraction, distillation, crystallization).

According to method b) a compound of the formula IV is reacted with formaldehyde, e.g. paraformaldehyde, and acetylene. The reaction is conveniently carried out in an ether of high boiling point (e.g. butyl ether or dioxane) in the presence of cuprous acetylide. The reaction is performed preferably at a temperature of 80 to 150"C. One may proceed preferably by dissolving the compound of the formula IV in dioxane, adding cuprous acetylide or a compound capable of forming cuprous acetylide (e.g. cuprous chloride) and introducing acetylene into the mixture under heating and stirring. The product of the formula I in which R3 is propargyl may be isolated by methods known per se.

The propynyl group may also be formed by subsequent modification of a halopropenyl derivative. Thus one may proceed by reacting a compound of the formula IV with an 1,2-dihalo-alkene (e.g.

1.2-dibromo-propane) to form a compound I in which R3 is 2-haloalkenyl and optionally when R3 is 2-halo-2-propenyl split off hydrogen halide from the derivative thus obtained, e.g. with an alkali metal hydroxide, alkaline earth metal hydroxide, or an organic base, to form a compound I in which R3 is propargyl.

The compounds of the formula I thus obtained may be converted into a pharmaceutically acceptable acid addition salt formed with an inorganic or organic acid. The product may also be purified through the salts by utilising the fact that the salts are crystalline, readily crystallisable substances. After purification the base is set free from the salt by treatment with an alkali. For salt-formation hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, maleic acid, lactic acid, citric acid or ascorbic acid, may e.g. be used.

Compounds of the formula I in which R' is an alkyl group contain an asymmetric carbon atom and may exist in racemic or optically active forms. The racemate may be subjected to resolution by conventional methods. The optically active compound of the formula I may also be prepared by using an optically active amine of the formula IV in the reactions a) and b).

According to a further feature of the present invention there are provided pharmaceutical compositions comprising as active ingredient a compound of the formula I or its pharmaceutically acceptable acid addition salt in admixture with solid or liquid pharmaceutically acceptable carriers or diluents. The compositions may be formulated in solid forms (e.g. tablets, pills, coated pills, capsules, drawees, powder mixtures) or liquid forms (e.g. aqueous solution or suspension). The compositions are suitable for oral or parenteral administration. The compositions contain conventional carriers, e.g. talc, calcium carbonate, magnesium stearate, water, petrolatum or polyalkylene glycols. The compositions can be prepared by conventional methods of pharmacy.

The N - methyl - N - [2 - (furyl - 2) ethyl - prop - 2 - nyl amine in an in vivo dose of 6.25 mg./kg. inhibits the oxidation of benzylamine in the liver to an extent of 79 /" and the oxidation of tyramine only by 44%.

In a dose of 5 mg./kg. N - methyl - N - [I methyl - 2 - (furyl - 2) - ethyl]prop - 2 - ynyl amine inhibits in the brain the oxidation of benzylamine to an extent of 53 / and that of 5-hydroxy-tryptamine only by 20/,. On the other hand the known compound N,alpha di - methyl - N - beta - phenyl - ethyl N - propynyl - amine causes in the same dose an inhibition by 800/ of the oxidation of benzylamine in the brain, while the inhibition of the oxidation of 5-hydroxytryptamine is 15%. The latter known phenyl derivative when administered in a dose of 10 mg/kg. inhibits the oxidation of benzylamine in the liver by 78%, and the oxidation of 5hydroxy tryptamine by 560/. The above data show that the compound of the formula I tested exhibited a more selective monoaminooxidase inhibiting effect, than the known phenyl derivative. According to in vitro tests the selectivity is also more pronounced.

The reserpine depression antagonising antidepressive effect of the compounds of the formula I which we tested is significantly stronger than that of the phenyl analogues.

The toxicity of the compounds of the formula I which we tested is lower, than that of the known phenyl derivatives, and therefore the compounds of the present invention possess a more advantageous therapeutic index and a broader spectrum of activity.

Further details of the present invention are to be found in the Examples without limiting the scope of our invention to the Examples.

Example I 7.9 g. (0.0568 mole) of N - methyl - N [1 - methyl - 2 - (furyl - 2) - ethyl]-amine are dissolved in 142 ml. of toluene, whereupon at 45 to 500C 6.7 g. (0.0568 mole) of propargyl bromide and 11.4 ml. of a 5 N aqueous sodium hydroxide solution are added at the same time under stirring.

The reaction mixture is refluxes under stirring for 3 hours. After cooling 14.8 ml. of a 10 N sodium hydroxide solution are added and the phases are separated. The aqueous layer is extracted twice with benzene, whereupon the benzene and toluene solutions are united, dried over anhydrous potassium carbonate and evaporated. The residue is dissolved in 50 ml. of benzene and refluxed with 6 g. of acetic anhydride for an hour. After cooling the solution is washed with a 20% sodium carbonate solution until the evolution of carbon dioxide ceases. The mixture is washed with water and extracted with 5% hydrochloric acid at OOC. The hydrochloric acid solutions are united, the mixture is allowed to stand at a temperature below 100C, and made alkaline. The separated oil is extracted with ether, the ether extract is dried over potassium carbonate and evaporated. On subjecting the residue to vacuum distillation 6.5 g. of Nmethyl - N - Ll - methyl - 2 - (furyl - 2) ethyl - prop - 2 - ynyl - amine are obtained.

Bp.: 115--117"C/20 Hgmm; n0=1.4922.

Example 2 The process according to Example I is carried out except that 12.5 g. of N methyl - N - 2 - (furyl - 2) - ethyl amine and 11.9 g. (0.1 mole) of propargyl bromide are reacted in 70 ml. of toluene and 20 ml. of a 5 N sodium hydroxide solution. Thus 11.2 g. of N - methyl - N - [2 - (furyl - 2)ethyl] - prop - 2 - ynyl amine are obtained.

Bp.: 105-1060C/20 Hgmm; n20-l 4891.

The melting point of the hydrochloride amounts to 106-1080C (from a mixture of ethanol and ether).

Example 3 To 13.9 g. (0.1 mole) ofN - methyl - N [I - methyl - 2 - (furyl - 2) - ethyl]amine 10 g. (0.05 mole) of 1,2-dibromo-propene are added dropwise, the reaction mixture is heated at 100"C for 7 hours, whereupon it is cooled to room temperature and dissolved in 5 gn hydrochloric acid. The acidic solution is extracted with ether and made alkaline with 40 /n sodium hydroxide. The precipitated oil is extracted with ether, the extract is dried and evaporated. To the residual brown oil 60 ml. of 40 /n sodium hydroxide and 30 ml. of benzoyl chloride are added simultaneously dropwise within 3045 minutes in order to benzoylate the unreacted N - methyl - N - [methyl - 2 (furyl - 2)- ethyl] amine. During the addition in the temperature of the reaction mixture rises to 50-600 C. The addition having been completed the reaction mixture is stirred at this temperature for an hour, whereupon it is cooled to room temperature and benzene is added. The mixture is shaken and the benzene phase is separated and extracted with 5% hydrochloric acid. The N methyl - N - [1 - methyl -2 - (furyl - 2) ethyl] - N - 2 - bromo - prop - 2 - enyl amine dissolves in the acidic phase, while the N - methyl - N - [I - methyl - 2 (furyl - 2) - ethyl] - benzoyl amine remains in the benzene solution. The hydrochloric acid layer is made alkaline, the precipitated N - methyl - N - [I - methyl - 2 - (furyl - 2) - ethyl] - N - 2 - bromo - prop - 2 enyl amine is extracted with benzene, dried and evaporated. The residue is distilled off in vacuo. Thus 7.1 g. of N - methyl - N -[I methyl - 2 - (furyl - 2) - ethyl] - N - 2 bromo - prop - 2 - enyl amine are obtained. The product is dissolved in 100 ml. of ethanol and 14 ml. of an 50% aqueous potassium hydroxide solution are added.

The reaction mixture is refluxed for 16 hours, whereupon the ethanol is distilled off and the residue is admixed with water and extracted with benzene. The benzene solution is dried over anhydrous potassium carbonate and evaporated. The residue is distilled off in vacuo. Thus 4.9 g. of N methyl - N - [I - methyl - 2 - (2 - furyl) ethyl - prop - 2 - ynyl amine are obtained.

Bp.: 114115 C/20 Hgmm; n2 =1.4915.

Example 4 12.5 g. (0.1 mole) of N - methyl - N - 2 (2 - furyl) - ethyl amine are reacted with 10 g. (0.05 mole) of 1,2 - dibromo - prop - 2 ene according to Example 3. Thus 7.6 g. of N - methyl - N - [2 - (2 - furyl) - ethyl] 2- bromo - prop - 2- enyl amine are obtained, which is reacted with 14 ml. of 50 /n aqueous potassium hydroxide in 100 ml. of ethanol under heating to boiling as described in Example 3. Thus 5.1 g. of N methyl - N - 12 - (2 - furyl)- ethyl] prop - 2 - ynyl amine are obtained. Bp.: l051060C/20 Hgmm; n2 =1.4890. The melting point of the hydrochloride amounts to l07-l080C (from a mixture of ethanol and ether).

Example 5 12.4 R. (0.1 mole) of 2-furyl-acetone are dissolved in 100 ml. of ethanol, whereupon 7.25 g. (0.105 mole) of methyl-propynyl amine are added. 3.5 A. of aluminium foil is degreased with ethanol and thereafter activated with a solution of 1 g. of mercuric chloride and 15 g. of sodium chloride in 30 ml. of water. The activating solution is decanted after 8 minutes and the activated aluminium foil is washed with cold water and added to the alcoholic solution previously prepared under stirring. An exothermic reaction takes place and the temperature is kept at 15 to 300C by cooling. The reaction mixture is stirred for 24 hours, whereupon 30 ml. of 40% sodium hydroxide are added. The two phases are separated, the lower aqueous phase is extracted three times with benzene. The benzene solutions are united with the previously separated alcoholic phase and evaporated. The residue consists of an organic oily layer and an aqueous phase which is extracted with benzene and the benzene solution is dried over potassium carbonate. The benzene is removed and the residue is distilled off in vacuo. Thus 6.7 g. of N - methyl - N- [I-methyl - 2 - (2 furyl) - ethyl] - prop - 2 - ynyl amine are obtained. Bp.: 113-115 C/20 Hgmm; n020=l .4905.

Example 6 13.9 g. (0. I mole) of N - methyl - N -[1 methyl - 2 - (2 - furyl) - ethyl] amine and 7 g.

(0.184 mole) of propargyl aldehyde are reacted in 100 ml. of ethanol in the presence of 3.5 g. of aluminium foil using the general method of Example 5. Thus 6.1 g. of Nmethyl - N - ll - methyl - 2 - (2 - furyl) - ethyl - prop - 2 - ynyl amine are obtained.

Bp.: 114-115 C/20 Hgmm; nD =1.4910.

Example 7 13.9 R. (0. I mole) of N - methyl - N -[I methyl - 2 - (2 - furyl) - ethyl] amine are dissolved in 80 ml. of dioxane, whereupon 6 g. of paraformaldehyde and I g. of cuprous chloride are added and gaseous acetylene is introduced into the solution at 80"C under stirring for 30 hours. The reaction mixture is filtered and the filtrate is evaporated. The residue is dissolved in benzene, the benzene solution is washed with water, dried over potassium carbonate and evaporated. The residue is distilled off in vacuo. Thus 6.8 g. of N - methyl - N - [I - methyl - 2 - (2 furyl) - ethyl] - prop - 2 - ynyl amine are obtained. Bp.: 11-116"C/20 HRmm; nD20=1.4910.

Example 8 12.8 g. (0.1 mole) of 1 - methyl - 2 - (2 furyl) - ethyl - chloride and 15 g. (0.208 moles) of methyl-propynyl amine are heated in a sealed bomb tube at 70 to 800C for 4 hours. The reaction mixture is cooled, 30 ml. of 40% sodium hydroxide are added and the mixture is extracted with benzene. The benzene solution is dried, evaporated and the residue is distilled off in vacuo. Thus 9.8 g.ofN - methyl - N - [I - methyl - 2 -(2 furyl)- ethyl] - propynyl amine are obtained. Bp.: 113--115"C/20 Hgmm; nD = 1.4904.

Example 9 11.45 g. (0.1 mole) of 2 - furyl - ethyl chloride are reacted with 15 g. (0.208 moles) of methyl-propynyl amine according to the method described in Example 8. Thus 8.8 g.

of N- methyl - N- [2 - (furyl - 2)ethyl[ - prop - 2 - ynyl amine are obtained.

Bp.: 104--1050C/20 Hgmm; nD =1.4868.

WHAT WE CLAIM IS: I. Racemic or optically active compounds of the formula I

and acid addition salts thereof (wherein Rl and R2 are independently hydrogen or C1- alkyl and R3 is C2-haloalkenyl, halo prop-2enyl or propargyl).

2. Compounds of the formula I wherein R3 is bromoprop-2-enyl.

3. Racemic or optically active Nmethyl - N - [I - methyl - 2 - (2 - furyl) ethyl] - prop - 2 - ynylamine and pharmaceutically acceptable acid addition salts thereof.

4. Racemic or optically active N methyl - N - [2 - (2 - furyl) - ethyl prop - 2 - ynylamine and pharmaceutically acceptable acid addition salts thereof.

5. Racemic or optically active N methyl - N - [1 - methyl - 2 - (furyl - 2) ethyl] - N - 2 - bromoprop - 2 - enylamine and pharmaceutically acceptable acid addition salts thereof.

6. Hydrochloride salts of a compound according to any of the preceding claims.

7. The D-isomer of a compound according to any of the preceding claims.

8. The L-isomer of a compound according to any one of claims I to 6.

**WARNING** end of DESC field may overlap start of CLMS **.

Claims

**WARNING** start of CLMS field may overlap end of DESC **.

2- bromo - prop - 2- enyl amine are obtained, which is reacted with 14 ml. of 50 /n aqueous potassium hydroxide in 100 ml. of ethanol under heating to boiling as described in Example 3. Thus 5.1 g. of N methyl - N - 12 - (2 - furyl)- ethyl] prop - 2 - ynyl amine are obtained. Bp.: l051060C/20 Hgmm; n2 =1.4890. The melting point of the hydrochloride amounts to l07-l080C (from a mixture of ethanol and ether).

Example 5 12.4 R. (0.1 mole) of 2-furyl-acetone are dissolved in 100 ml. of ethanol, whereupon 7.25 g. (0.105 mole) of methyl-propynyl amine are added. 3.5 A. of aluminium foil is degreased with ethanol and thereafter activated with a solution of 1 g. of mercuric chloride and 15 g. of sodium chloride in 30 ml. of water. The activating solution is decanted after 8 minutes and the activated aluminium foil is washed with cold water and added to the alcoholic solution previously prepared under stirring. An exothermic reaction takes place and the temperature is kept at 15 to 300C by cooling. The reaction mixture is stirred for 24 hours, whereupon 30 ml. of 40% sodium hydroxide are added. The two phases are separated, the lower aqueous phase is extracted three times with benzene. The benzene solutions are united with the previously separated alcoholic phase and evaporated. The residue consists of an organic oily layer and an aqueous phase which is extracted with benzene and the benzene solution is dried over potassium carbonate. The benzene is removed and the residue is distilled off in vacuo. Thus 6.7 g. of N - methyl - N- [I-methyl - 2 - (2 furyl) - ethyl] - prop - 2 - ynyl amine are obtained. Bp.: 113-115 C/20 Hgmm; n020=l .4905.

Example 6 13.9 g. (0. I mole) of N - methyl - N -[1 methyl - 2 - (2 - furyl) - ethyl] amine and 7 g.

(0.184 mole) of propargyl aldehyde are reacted in 100 ml. of ethanol in the presence of 3.5 g. of aluminium foil using the general method of Example 5. Thus 6.1 g. of Nmethyl - N - ll - methyl - 2 - (2 - furyl) - ethyl - prop - 2 - ynyl amine are obtained.

Bp.: 114-115 C/20 Hgmm; nD =1.4910.

Example 7 13.9 R. (0. I mole) of N - methyl - N -[I methyl - 2 - (2 - furyl) - ethyl] amine are dissolved in 80 ml. of dioxane, whereupon 6 g. of paraformaldehyde and I g. of cuprous chloride are added and gaseous acetylene is introduced into the solution at 80"C under stirring for 30 hours. The reaction mixture is filtered and the filtrate is evaporated. The residue is dissolved in benzene, the benzene solution is washed with water, dried over potassium carbonate and evaporated. The residue is distilled off in vacuo. Thus 6.8 g. of N - methyl - N - [I - methyl - 2 - (2 furyl) - ethyl] - prop - 2 - ynyl amine are obtained. Bp.: 11-116"C/20 HRmm; nD20=1.4910.

Example 8 12.8 g. (0.1 mole) of 1 - methyl - 2 - (2 furyl) - ethyl - chloride and 15 g. (0.208 moles) of methyl-propynyl amine are heated in a sealed bomb tube at 70 to 800C for 4 hours. The reaction mixture is cooled, 30 ml. of 40% sodium hydroxide are added and the mixture is extracted with benzene. The benzene solution is dried, evaporated and the residue is distilled off in vacuo. Thus 9.8 g.ofN - methyl - N - [I - methyl - 2 -(2 furyl)- ethyl] - propynyl amine are obtained. Bp.: 113--115"C/20 Hgmm; nD = 1.4904.

Example 9 11.45 g. (0.1 mole) of 2 - furyl - ethyl chloride are reacted with 15 g. (0.208 moles) of methyl-propynyl amine according to the method described in Example 8. Thus 8.8 g.

of N- methyl - N- [2 - (furyl - 2)ethyl[ - prop - 2 - ynyl amine are obtained.

Bp.: 104--1050C/20 Hgmm; nD =1.4868.

WHAT WE CLAIM IS: I. Racemic or optically active compounds of the formula I

and acid addition salts thereof (wherein Rl and R2 are independently hydrogen or C1- alkyl and R3 is C2-haloalkenyl, halo prop-2enyl or propargyl).
2. Compounds of the formula I wherein R3 is bromoprop-2-enyl.
3. Racemic or optically active Nmethyl - N - [I - methyl - 2 - (2 - furyl) ethyl] - prop - 2 - ynylamine and pharmaceutically acceptable acid addition salts thereof.
4. Racemic or optically active N methyl - N - [2 - (2 - furyl) - ethyl prop - 2 - ynylamine and pharmaceutically acceptable acid addition salts thereof.
5. Racemic or optically active N methyl - N - [1 - methyl - 2 - (furyl - 2) ethyl] - N - 2 - bromoprop - 2 - enylamine and pharmaceutically acceptable acid addition salts thereof.
6. Hydrochloride salts of a compound according to any of the preceding claims.
7. The D-isomer of a compound according to any of the preceding claims.
8. The L-isomer of a compound according to any one of claims I to 6.
9. Compounds according to claim 1,

substantially as herein before described.
10. A process for the preparation of compounds of the formula I as defined in claim land acid addition salts thereof which comprises reacting a corresponding compound of the formula 11

with a compound of the formula Ill B-R3 (Ill) (wherein R', R2, R3 are as defined in claim I, and A and B represent groups which on reacting with each other, are capable of forming the bivalent group R2-N= and if desired converting a C3-halo-alkenyl group at R3 in the product obtained into a prop-2ynyl group.
11. A process according to claim 10, which comprises reacting a compound of the formula IV

(wherein R1 and R2 are as defined in claim 1) with a compound of the formula III (wherein R3 is propargyl and B is halogen or a sulfonic acid ester group) to form a compound I in which R3 is propargyl.
12. A process according to claim 11 wherein B is alkylsulfonyloxy or arylsulfonyloxy.
13. A process according to claim 11, wherein B is chlorine, bromine, methanesulfonyloxy or ptoluenesulfonyloxy.
14. A process according to claim 10, which comprises reacting a compound of the formula IV as defined in claim 11 with a 1,2-dihaloalkene to form a compound I in which R3 is 2-halo-alkenyl and when R3 is 2halo-2-propenyl optionally splitting off hydrogen halide from the halo-alkenyl derivative thus obtained to form a compound I in which R3 is 2-propynyl.
15. A process according to claim 10 which comprises reacting a compound of the formula IV as defined in claim 11 with propargyl aldehyde with simultaneous or subsequent reduction of the imine formed to yield a compound I in which R3 is propargyl.
16. A process according to claim 10, which comprises reacting a compound of the formula

with a compound of the formula V

wherein R', R2 and R3 are as defined in claim 1, with simultaneous or subsequent reduction of the imine formed.
17. A process according to claim 10, which comprises reacting a compound of the formula VII

with a compound of formula V as defined in claim 16 (wherein Rs, R2 and R3 have the same meanings as in claim 1, and X is halogen or a sulfonic acid ester group).
18. A process according to claim 17 wherein X is chlorine, bromine, alkylsulfonyloxy or arylsulfonyloxy.
19. A process according to claim 17, which comprises reacting a 2-furyl-ethyl halide with methylpropynylamine.
20. A process according to any of claim 11--13 or 17-19 wherein an acid binding agent is present in the reaction mixture.
21. A process for the preparation of compounds of the formula I as defined in.

claim I in which R3 is propargyl and acid addition salts thereof which comprises condensing a compound of the general formula IV as defined in claim 11 with formaldehyde and acetylene.
22. A process according to claim 21 wherein said condensation is performed at 80-1500C in a high boiling ether in the presence of cuprous acetylide.
23. A process according to any of claims 10-22 wherein the product of formula I thus obtained is salified or desalified.
24. A process according to any of claims 10-23 wherein the product of formula I wherein R1 is C14-alky1 thus obtained is resolved.
25. A process according to any of claims II to 15 or 21 to 23 wherein an optically active amine of the general formula IV as defined in claim 11 wherein R' is Cm 4alkyl is used as starting material.
26. A process according to claim 10 or 21, substantially as hereinbefore described.
27. A process according to claim 10 or 21, substantially as hereinbefore described with reference to any one of the Examples.
28. Compounds of the formula I whenever prepared according to the process of any of claims 10 to 27.
29. Pharmaceutical compositions comprising as active ingredient a racemic or optically active compound of the formula I (wherein R1, R2 and R3 are as defined in claim 1) or a pharmaceutically acceptable acid addition salt thereof in admixture with solid or liquid pharmaceutically acceptable carriers or diluents.
30. Pharmaceutical compositions according to claim 29, in the form of tablets, pills, coated pills, dragees, capsules, powders or aqueous solutions or suspensions.
31. Pharmaceutical compositions according to claim 29 or 30 comprising the compound of claims 3 or 4.
32. Pharmaceutical compositions according to claim 29 or 30 comprising the compound of claim 5.