NO850897L - PROCEDURE FOR PREPARING A RELATIONSHIP WITH EFFECT ON MAVESAR - Google Patents

Description

The present invention specifies a method for the preparation of the compound N-(2-(((5-(dirnetylamino)methyl)

-2-furanyl)methyl)thio)ethyl)-N'-(3,4-methylenedioxobenzyl)-2-nitro-1,1-ethylenediamine of the formula (I)

Said compound described in the Italian Patent Application

no. 23546 A/81, in the applicant's name, which exhibits high activity against stomach ulcers and with practically no toxicity, can be produced according to the invention with a high yield and with greater purity compared to the method described in said application 23546 A/81 in which the reaction between 2-((2-amino-ethyl)thio-methyl)-5-(dimethylaminomethyl)-furan and 1-nitro-2-methylthio-2-(3,4-methylenedioxybenzylamino)-ethene was reported.

According to one embodiment of the invention, 2-(dimethylaminomethyl)-5-(R-methyl) furan (formula II) is reacted

where R is hydroxyl, halogen, dimethylamino or trimethylammonium iodide, with a compound of formula (III)

where X may be 0, S or a group of formula CH-NC^.

When X is CH-NC^ the group produces compound I directly but when X is oxygen or sulphur, treatment with nitro methane to the compound obtained by reacting (II) and (III) gives compound I.

The intermediate compound of formula III where X is CH-NO2 can be prepared starting from l-nitro-2,2-bis

-(methylthio)-ethene or from 2-(nitromethylene)-thiazolidine, according to the following reaction patterns:

in the above scheme, l-nitro-2,2-bis-(methylthio)-ethene (formula IV) is reacted with 3,4-methylenedioxybenzylamine (formula V) to give l-nitro-2-methylthio-2-(3 ,4-methylenedioxybenzylamino)ethene (formula VI) which is treated with ammonia to give N-(3,4-methylenedioxybenzyl)-1-nitroethylenediamine (formula VII) and the latter, added with ethylene sulphide, gives the intermediate formula III.

Alternatively, the compound VI can be suitably reacted with cystamine or 2-aminoethanethiol, thereby directly intermediate

mediate III.

Another scheme (Scheme 2) consists of treating l-nitro-2,2

-bis-(methylthio)-ethene (formula IV) with ammonia to give 1-nitro-2-amino-2-methylthio-ethene (VIII) which is reacted with ethylene sulfide to give 1-nitro-2-methylthio-2- (2-mercaptoethylamino)-ethene (formula IX) which in turn is treated with 3,4-methylenedioxy-benzylamine (V) to give intermediate (III):

Compound IX can also be reacted with one of the compounds of formula II, thereby giving the intermediate with the following formula:

which, on treatment with 3,4-methylenedioxy-benzylamine (V), gives compound I.

Finally, method 3, which is much simpler and faster, gives intermediate (III) by reacting 2-(nitromethylene)-thiazolidine (formula X) a known compound (French patent no. 2,384.

765; Ger. Open. No. 2,734,070; SB: Soloway et al. - Pestic. Venom. Neuz.-15^ Congr. Single. 1976, 153 - (CA. 89, 101812-1978) and Chem. Abstract 99, 70613v), with 3,4-methylenedioxybenzylamine (formula V).

The intermediate of formula III wherein X is oxygen has in turn been obtained by reacting 3,4-methylenedioxybenzylamine (formula V) with N,N-carbonyldiimidazole, which gives N-(3,4-methylenedioxybenzyl)imidazole -carbonylamide (formula IX), the preparation of which is not necessary, but which is directly reacted with cyctamine or 2-aminoethanethiol, giving the desired intermediate III (X = 0) according to the following scheme:

In a similar manner, but in higher yield, urea III has been obtained by reacting N-(3,4-methylenedioxybenzyl)imidazole-carbonylamide (formula XI) with cystamine or 2,2'-diaminodiethyl sulfide (formula XII) in a 2 :1 ratio, thereby providing 2,2<1->bis-(3,4-methylenedioxybenzylaminocarbonylaminoethyl)disulfide (formula XIII) which, by simple reduction with zinc and acetic acid, gives the intermediate III

The intermediate of formula III wherein X is sulfur is obtained, on the other hand, by condensing 3,4-methylenedioxybenzylisothiocyanate with cystamine.

The intermediates II are known and can be obtained according to E.W. Gill et al. (J. Chem. Soc. 1958, 4728) and 0. Moldenhauer et al. (Ann. 580, 169, 1953) with obvious changes in relation to the methods described herein.

According to a modification of the methods described above for the preparation of compound I, the compounds of formula III with R = chlorine or hydroxyl can be converted into the compound with R = SH, which can be reacted with the compound of formula:

which in turn can be obtained from compound VII or VIII by reaction with ethylene oxide.

According to another embodiment, compound I is prepared by starting from 2-(dimethylaminoethyl)-5-(2-hydroxyl)ethylthiomethylfuran (formula XIV) with 2-amino-2-(3,4-methylenedioxybenzylamino)-1 -nitro-ethene (formula VII, scheme 1) in the presence of Raney nickel, according to the following scheme:

Compound XIV can optionally be transformed into the corresponding tosylate, which is then reacted with the compound

(VII) .

Compound XIV and its tosylate are disclosed in Italian Patent Application No. 20461 A/82.

The following examples further illustrate the invention without limiting it.

Example 1

a) l-Nitro-2-(3,4-methylenedioxybenzylamino)-2-(2-mercapto-ethylamino)ethene - (formula III: X = CH-NO2; Scheme 1) l-nitro-2,2-bis- (methylthio)-ethene (33.05 g; 0.2 mol) is added to 1,1,2-trichloroethylene (200 mL) and the mixture is refluxed to achieve complete homogeneity. 3,4-methylenedioxybenzylamine (15.1 g; 0.1 mol) dissolved in the same solvent (100 ml) is then added to the boiling solution. Boiling under reflux is maintained for a further 90 min. whereupon the solvent is distilled off under reduced pressure and the resin is purified by means of silica gel column chromatography, first eluted with petroleum ether and then with dichloromethane. 1-nitro-2-methylthio-2-(3,4-methylenedioxybenzylamino)-ethene (formula VI) is crystallized from dichloromethane ether. The analytically pure product (16.7 g; 62% yield) melts at 118-119°C (incorrect).

Sulfur (Schoeniger) = lime. % 11.95; found % 12.00.

The previously obtained compound (15.0 g; 0.056 mol) is added to concentrated ammonia (200 ml) and the mixture is stirred at room temperature for approx. 48 hours. After evaporation under reduced pressure, becomes. the obtained crude product used in the following step: in any case, 1-nitro-2-amino-2-(3,4-methylenedioxybenzylamino)-ethene (formula VII) can be crystallized from an alcohol, preferably 2-propanol (12.9 g; yield 97%).

The mercaptoethylation of the above-mentioned compound has been carried out with ethylene sulphide according to the method described by H.R. Snyder et al. (J. Am. Chem. Soc. 69, 2672-1947)

1-nitro-2-amino-2-(3,4-methylenedioxybenzylamino)-ethene, previously prepared (11.8 g; 0.05 mol), toluene (50 ml) and ethylene sulfide (3.0 g; 0.05 mol) ), are mixed in a flask under pressure. After closing the flask, the mixture is heated to 90-100°C for 24 hours with stirring. After cooling and evaporation at reduced pressure, the crude product is obtained which is purified according to the method of W.C. Still et al.

(J. Org. Chem. 43, 2923-1978)).

Elemental analysis: for<C>^2<H>15N304<S>(297.33)

Calculated % : C = 48.47; H = 5.08; N = 14.13; S = 10.78;

Found % : C = 48.62; H = 5.12; N = 14.10; S = 10.52. b) 2-(dimethylaminomethyl)-5-chloromethyl-furan (formula II):

R = CI)

2-(Dimethylaminomethyl)-5-hydroxymethylfuran (15.6 g; 0.1 mol) prepared as described by E.W. Gill et al. (J. Chem. Soc. 1958, 4728), is dissolved in dichloromethane (100 ml) and the solution is treated first with non-aqueous hydrochloric acid, then with phosphorus pentachloride at room temperature and in a heterogeneous phase. After approx. After 4 hours, the chlorination is complete. The solid is collected and carefully washed on a filter with dichloromethane to remove the phosphorus halides. The base is obtained by careful alkalization with 20% aqueous sodium hydroxide and is extracted with dichloromethane. The organic solution, washed with water, dried (Na2SO^)

and evaporated gives an oily residue (14.0 g; yield 80.6 %).

Chlorine (Schoeniger)- - calculated % = 20.42; found % = 20.77.

c) N-(2-(((5-((Dimethylamino)methyl-2-furanyl)methyl)-thio)ethyl)-N'-(3,4-methylenedioxybenzyl)-2-nitro-1,1-ethenedia -min) (Formula I)

Metallic sodium in small pieces (1.15 g; 0.05 g.a.) is dissolved under a nitrogen atmosphere in absolute methanol (200 ml). When all the metal has dissolved, 1-nitro-2-(3,4-methylenedioxybenzylamino)-2-(2-mercaptoethylamino)ethene (14.8 g; 0.05 mol) is added. After heating to boil under reflux for approx. 20 min. the mixture is cooled and 2-(dimethylaminomethyl)-5-chloromethyl-furan (8.7 g; 0.05 mol) dissolved in absolute methanol (50 ml) is slowly added with stirring.

The mixture is heated to 50-80°C for approx. 2 hours to complete the reaction, then water is added still under the same temperature to slight turbidity. The mixture is then left to cool and then overnight in the cold.

The crystallized product which melts at 98-102°C (not correct) is obtained with a yield of 16.3 g (75%).

Elemental analysis for<C>20<H>26<N>4<O>,<->S (454.51)

Calculated % C = 55.29; H = 5.99; N = 12.90; S = 7.05

found % C = 55.39; H = 6.02; N = 12.79; S = 7.10

"'"The H-NMR spectrum confirms the structure of the compound:

(internal reference TMS; solvent DMSO):

2.1, p, 6H; 2.7, m, 4H; 3.4, p, 2H; 3.7, d, 2H; 3.85, p, 2H; 4.3, p, 2H; 6-7, m, 6H arom. and CHN02;8 and 10,s wide, 2H.

The connection is consequently identical to that obtained according to Italian patent application No. 23546 A/81.

Example 2

a) 1-nitro-2-(3,4-methylenedioxybenzylamino)-2-(2-mercapto-ethylamino)-ethene (Formula III: X = CH-NO2; Scheme 3)

2-(nitromethyl)thiazolidine (French Patent No. 2,384,765; Ger. Offen. No. 2,734,070; S.B. Soloway et al. - Pestic. venom. neurotox. 153, 1976-C.A. 89, 101812) (7.3 g; 0.05 mol) is dissolved in a high-boiling apolar solvent, preferably toluene or xylene (100 ml). The mixture is boiled

under reflux under an inert atmosphere whereupon 3,4-methylenedioxybenzylamine (15.1 g; 0.1 mol) is added dropwise in 30

-40 min. When the feed is over, continue boiling under reflux for approx. 12 hours after which the mixture is cooled, filtered and the filtrate is washed with water, 10% dilute hydrochloric acid, water, 5% aqueous sodium hydroxide, then with water again and after drying (MgSO^), the solvent is evaporated off under vacuum. The residue, mainly consisting of the crude product, is purified on silica gel (70-230 mesh) column chromatography eluted with ethyl acetate-petroleum ether. The analytically pure compound is obtained (10.1 g; yield 68%)

Elemental analysis for<c>i2<H>15N3°4<S>(297-33)

Calculated % : C = 48.47; H = 5.08; N = 14.13; S = 10.78 Found % : C = 48.53; H = 5.15; N = 14.08; S = 10.48 identical to that found in example 1.

b) N-(2-(((5-((dimethylamino)methyl)-2-furanyl)methyl)-thio)ethyl)N1 -(2,4-methylenedioxybenzyl)-2-nitro-1,1-ethenedia- min (Formula I)

By reacting the intermediate III previously prepared in the same way as described in example I, the compound identical to that from example I is obtained (yield 72%).

Example 3

a) 2,5-bis-(dimethylaminoethyl)furan monoiodomethylate (formula II, R = N<+>(CH3)3I~)

2,5-bis-(dimethylaminomethyl)furan (9.9 g; 0.05 mol) prepared as described by E.W. Gill et al. (J. Chem. Soc. 1958, 4728) is dissolved in anhydrous acetonitrile (100 ml). Iodomethane (7.1 g; 0.05 mol) is added dropwise to the solution. After approx. 30 min. the quaternary ammonium salt begins to crystallize which is then collected and crystallized from an alcohol, preferably ethanol (12.1 g; 71% yield) lead (AgN03): Calculated'% = 37.3; found % = 36.9.

b) N-(2-(((5-(dimethylamino)methyl)-2-furanyl)methyl)-thio)ethyl)-N'-(3,4-methylenedioxybenzyl)-2-nitro-1,1-ethene -diamine (formula I)

The previously obtained iodide ethylate (6.8 g; 0.02 mol)

dissolve in dimethylformamide (80 ml). 1-nitro-2-(3,4-methylene dioxybenzylamino)-2-(2-mercaptoethyleneamino)ethene, prepared according to example 2a) (5.9 g; 0.02 mol), is added to the solution.

The mixture is heated with stirring at 80-120°C under an inert atmosphere for approx. 1 day. After cooling, the reaction liquid is poured into water and into ice, which produces separation of tough particles which are collected by decantation, washed again with water and crystallized from aqueous ethanol (6.5 g; yield 72%) : melting point 98-102°C (incorrect ).

The compound found is identical to that prepared in Example I.

Example 4

a) 2-(dimethylaminomethyl)-5-chloromethyl-furan (formula II:

R = CI)

2,5-bis-(chloromethyl)furan (16.5 g; 0.1 mol), obtained as described by O. Moldenhauer et al. (Ann 580, 169-1953), dissolve in ether (200 ml) and add dimethylamine hydrochloride (8.1 g; 0.1 mol). The mixture is cooled to 0-5°C, anhydrous potassium carbonate (27.6 g; 0.2 mol) is also added in small amounts with vigorous stirring, by maintaining the same temperature and by ensuring that gas evolution stops between one addition and the next. When the additions are over, the temperature rises to room temperature and the mixture is stirred for a further 2 hours.

The inorganic salts present are filtered and the filtrate is evaporated under reduced pressure. The obtained crude product contaminated by bis-substituted compounds is purified by the method of W.C. Still et al. (J. Org. Chem. 43, 2933, 1978). The desired pure product is obtained as a dense oil (12.4 g; 72% yield), which is almost colorless.

Chlorine (Schoeniger): Calculated % = 20.42; found 20.33.

b) N-(2-(((5-(dimethylamino)methyl)-2-furanyl)methyl)-thio)ethyl)-N'-(3,4-methylenedioxybenzyl)-2-nitro-1,1-ethene -diamine (formula I)

By using the same method as in example 1, the compound of formula I identical to that in example 1 is obtained (yield 81

Example 5

a) N-(2-mercaptoethyl)-N'-(3,4-methylenedioxybenzyl)urea

(formula III, X = O)

3,4-methylenedioxybenzylamine (15.1 g; 0.1 mol) and N,N'-carbonyldiimidazole (16.2 g; 0.1 mol) are dissolved in anhydrous chlorine form (200 ml). The solution is stirred at room temperature for approx. 30 min. and is then added cystamine or 2-aminoethanethiol (7.7 g; 0.1 mol), dissolved in anhydrous chloroform (50 ml). The mixture is stirred for a further 30 min., then filtered, and then the filtrate is washed with water, 10% hydrochloric acid, again water, dried (MgSO 4 ) and the solvent is then evaporated. The crude product obtained is crystallized from a mixture of ethanol-petroleum ether, which gives the analytically pure product (13.2 g; 52% yield).

Sulfur (Schoeniger): Calculated % 12.61; found % 12.44.

The same intermediate can be obtained by an analogous procedure, but with a higher yield ((75-80%) by using cystamine or 2,2'-diaminodiethyldisulfide (formula XII) instead of 2-aminoethanethiol. N,N'- bis-(3,4-methylenedioxybenzyl)-cystamine (formula XIII) is then cleaved to 2 moles of mercaptan with zinc and acetic acid as described by CF. Allen et al. Org. Synth.-coil. vol. II, page 580.

b) N-(2-(((5-((dirnethylamino)methyl)-2-furanyl)methyl)-thio)ethyl)-N'-(3,4-methylenedioxybenzyl)urea

Metallic sodium in small pieces (about 6 g; 0.025 mol) is dissolved in absolute ethanol (100 ml). When all the metal has dissolved, the previously prepared N-(2-mercaptoethyl)-N'-(3,4-methylenedioxybenzyl)urea (6.35 g; 0.025 mol) is added to the solution. The mixture is heated with stirring for 15 min. and after cooling, carefully add 2-(dimethylamino-methyl)-5-chloromethyl-furan (4.35 g; 0.025 mol) dissolved in absolute ethanol (20 ml). The mixture is dissolved at about 70°C for 2 hours, then cooled and water is added to slight turbidity. After one night in the cold, the crystallized material (7.40 g; yield 75.8%) is collected and used in the next passage.

A sample has been recrystallized for elemental analysis.

Elemental analysis: for<C>19<H>25N3°4<S>(391.49)

Calculated % : C = 58.29; H = 6.43; N = 10.73; S = 8.18 Found % : C = 58.52; H = 6.25; N = 10.79; S = 8.10

c) N-(2-(((5-((dimethylamino)methyl)-2-furanyl)methyl)-thio)ethyl)-N'-(3,4-methylenedioxybenzyl)-2-nitro-1,1- ethenedi-amine (formula I)

Nitromethane (3.5 g; 2.7 ml; 0.05 ml) and the previously prepared urea derivative (19.5 g; 0.05 mol) are introduced into a bottle immersed in an ice-salt bath; and methanol (50 ml) and a solution of sodium hydroxide (2.1 g) in the same volume of previously cooled water are added to the mixture, the latter slowly so that the temperature does not exceed 10-15 C. During the addition, a precipitate forms which can be diluted with more methanol.

After stirring for 1 hour, dilute hydrochloric acid is added to neutrality and then water to slight turbidity; After standing overnight in the cold, the crystallized product is collected which, if it is not pure enough, is recrystallized from aqueous ethanol (16.9 g; 77.8%)• melting point 98-102°C (incorrect). The compound is identical to that found in example 1.

Example 6

N-(2-(((5-(dimethylamino)methyl)-2-furanyl)methyl)thio)-ethyl)-N'-(3,4-methylenedioxybenzyl(-2-nitro-1,1-ethenediamine)

(Formula I)

' 2-(dimethylaminoethyl)-5-((2-hydroxy)ethylthio-methyl)-furan (4.30 g; 0.02 mol), obtained as reported in Italian Patent Application No. 20461 A/82 and 2-amino-2-(3 ,4-methylene-dioxybenzylamino)-1-nitro-ethene (VII) prepared according to example la) (6.43 g; 0.025 mol) is dissolved in anhydrous toluene (100 ml) under heating.

Anhydrous Raney nickel (2.5 g) is added and the mixture is refluxed with stirring for 12 hours. After cooling, the catalyst is filtered off and the filtrate is evaporated to dryness. The crude product is then crystallized from aqueous ethanol to purity (6.18 g; 68% yield): mp 98-102°C (incorrect). The compound is identical to that obtained in example 1.

Example 7

a) 2-dimethylamino-methyl-5-(2'-tosyloxyethyl)-thiomethyl-furan.

The compound has been prepared as described in Italian Patent Application No. 20461 A/82 in 86% yield.

Sulfur (Schoeniger): Calculated % = 17.35; found % = 17.24.

b) N-(2-(((5-((dimethylamino)methyl)-2-furanyl)methyl)thio)ethyl)-N'-(3,4-methylenedioxybenzyl)-2-nitro-1,1-ethene -diamine (formula I)

The tosylate previously obtained (7.4 g; 0.02 mol) is dissolved in acetonitil (70 ml). 2-amino-2-(3,4-methylenedioxybenzyl-amino)-1-nitro-ethylene (5.22 g; 0.022 mol) is added to the solution. The mixture is refluxed with stirring for 15 hours and the solvent is then evaporated under reduced pressure. The crude product thus obtained is purified by silica gel column chromatography and eluted with ethyl acetate-methanol (7:3). The product obtained (5.3 g; 60.9% yield) can be crystallized from aqueous ethanol; melting point 98-102°C; mixed melting point with the compound obtained in Example 1: 98-102°C.

Example 8

a ) 3,4-Methylenedioxybenzyl isothiocyanate

Carbon disulfide (38.1 g; 30.2 ml; 0.5 mol) and a cold solution of sodium hydroxide (20 g; 0.5 ml) in water (45 ml) are added to a flask immersed in an ice bath.

The mixture, which is at 10-15 °C, is fed with 3,4-methylenedioxy benzylamine (75 g; 0.5 ml) in approx. 30 min. Stirring is maintained for a further 30 min. and the mixture is then boiled under reflux for approx. 2 hours. After cooling to 35°C, ethyl chlorocarbonate (54.2 g; 47.5 ml; 0.5 mol) is added slowly, and stirring is maintained for a further 30 min. at the same temperature.

When the reaction mixture has cooled to room temperature, it is transferred to a separation tube and the supernatant is separated from, dried (Na9SO.) and the more volatile part is removed at 35-40 0C under vacuum to give the product sufficiently pure for the following steps (73.5 g ; 76% yield)

b) N-(2-mercaptoethyl)-N'-(3,4-methylenedioxybenzyl)urea

(formula III: X = S)

A solution of 3,4-methylenedioxyisothiocyanate (19.3 g; 0.1 mol) in dichloromethane (80 ml) is cooled to 5°C. 2-Aminoethanethiol (7.7 g; 0.1 mol) diluted with dichloromethane (50 ml) is added to the solution. The addition is carried out slowly so that the reaction liquid does not exceed 10°C. When the addition is complete, stirring is maintained for 1 hour while the temperature is allowed to rise to room temperature. The reaction liquid, transferred to a separation tube, is washed with water, 10% hydrochloric acid, water again, dried (MgSO 4 ), filtered and evaporated, giving the crude product as a residue which is purified according to Still et al. (J. Org. Chem. 43, 2923-1978). The product obtained (18.4 g;

68% yield) is pure enough for the following steps.

Sulfur (Schoeniger): Calculated % = 23.71; found % = 23.83

c) N-(2-(((5-((dirnethylamino)methyl)-2-furanyl)methyl)thio)-ethyl)-N'-(3,4-methylenedioxybenzyl)thiourea

By reacting the previously prepared thiourea with 2-(dimethylaminomethyl)-5-chloromethyl-furan (II, R = CI) in the presence of sodium ethoxide, as described in example 5b), the title compound is obtained. (77% yield).

Elemental analysis: for<C>19<H>25<N>3<0>3<S>2 (40V/55)

Calculated % : C = 55.99; H = 6.18; N = 10.31; S = 15.73 Found % : C = 60.11; H = 5.99; N = 10.29; S = 15.56

d) N-(2-(((5-((dimethylamino)methyl)-2-furanyl)methyl)-thio)ethyl)-N'-(3,4-methylenedioxybenzyl)-2-nitro-1,1- ethylenediamine (formula I)

By working in the same way as in example 5c), the compound of formula I has been obtained in 81% yield, similar to that obtained in example 1; melting point 98-102^C melting point (mixed): 98-102°C.

Claims (10)

1. Method for the preparation of N-(2-(((5-((dimethylamino)-methyl)-2-turanyl)methyl)thio)ethyl)-N'(3,4-methylenedioxybenzyl-2-nitro-1, 1-Ethenediamine, of formula I characterized in that compounds of formula II wherein R is hydroxyl, halogen, dimethylamino or trimethylammonium iodide, is reacted with compounds of formula III in which X can be 0, S or a group of formula CH-NG^ and in that when X is 0 or S, the compound obtained is reacted with nitromethane. 2. Method according to claim 1, characterized in that the compound in formula II R is Cl. 3. Method according to claim 1, characterized in that in the compound of formula II R is OH. 4. Method according to claim 1, characterized in that in connection with formula II R is (CH3 )2 N- or (CH_,) 3N+l" . 5. Method for producing the intermediate of formula III where X = CH-NC>2 starting from 1-nitro-2, 2-bis-(methyl-thio)-ethene characterized in that one of the two methylthio groups is substituted by 3 , 4-methylenedioxybenzylamine, and the other by ammonia or cystamine and that, when one of the two methylthio groups is substituted with ammonia, the nitroethenamine obtained is reacted with ethylene sulphide. 6. Method for preparing the intermediate of formula III with X = CHNC>2 characterized in that 2-(nitromethylene)-thiazolidine of formula X is reacted with 3,4-methylenedioxybenzylamine. 7. Method for producing the intermediate of formula III with X=0 characterized in that N-(3,4 -methylenedioxybenzyl)imidazolecarbonylamide (XI) is obtained from 3,4-methylenedioxybenzylamine and N,N'-carbonyldiimidazole is reacted with cystamine or with 2,2'-diaminodiethyldisulfide and that, when 2,2'-diaminodiethyldisulfide is used, the ratio 2:1 is used and that the reaction product is subjected to reduction. 8. Method for producing the intermediate of formula III with X = S, characterized in that 3,4-methylenedioxybenzyl isothiocyanate is reacted with cystamine. 9. Method for producing the compound of formula I characterized in that 2-(dimethylaminomethyl)-5-(2-hydroxy)-ethyl-thiomethyl-furan (XIV) or the corresponding tosylate is reacted with 2-amino-2- (3,4-methylene dioxybenzylamino)-1-nitro-ethene (VII), in the presence of Raney nickel. 10. Method for producing the compound of formula I characterized in that 3,4-methylenedioxy-benzylamine is reacted with the compound of formula