HU180082B - Process for producing nitropyrrole derivatives - Google Patents

Description

The present invention relates to a process for the preparation of nitropyrrole derivatives having β-histamine receptor-antagonist activity.

Certain physiologically active substances exert their biological activity by interacting with specific regions known as receptors.

Histamine has such anypg and has complex biological effects. Such biological effects of histamine, which are inhibited by certain substances commonly referred to as "antihistanins" and are typically mediated by mepiramine, diphenhydramine and chlorpheniramine, Ib-histamine receptors. However, other biological effects of histamine are not inhibited by "antihistamines" and such effects, which are mediated by the burimanide barrier, are mediated by receptors called H ₂ -histamine receptors and these are H ₂ receptors that are are defined as receptors that are not blocked by mepiramine but blocked by burimanide. Compounds that block H ₂ -histamine receptors are referred to as H ₂ -histamine receptor antagonists.

Blocking the H ₂ histamine receptors is of great importance in inhibiting the biological effects of histamine that are not inhibited by "antihistamines". H ₂ -histamine receptor antagonists are therefore, for example, identical in that they interfere with gastric acid secretion and are valuable as anti-inflammatory agents and as substances that act on the cardiovascular system, such as inhibiting the action of histamine on blood pressure.

The present invention relates to a process for the preparation of nitropyrrole derivatives of the formula I wherein there are seven 5-methylimidazolyl, 3-chloro-2-pyridyl or 5-dimethylaminomethyl-2-furyl groups,

R ^{3 is} hydrogen, lower alkyl, phenyl, benzyl or phenylethyl. The term "lower alkyl" refers to C 1-4 alkyl groups which are straight or branched.

Representative examples of the compounds of the present invention include the following derivatives:

2- [2- (5-methyl-4-imidazolylmethylthio) -etilair.ino] -3-nitro-pyrrole,

2- [2- (5-methyl-4-imidazolylmethylthio) ethylamino] -3-nitro-4-methylpyrrole,

2- [2- (5-methyl-4-imidazolylmethylthio) ethylamino] -3-nitro-4-benzilpirrol,

2- [2- (5-methyl-4-imidazolylmethylthio) ethylamino] -3-nitro-4- (2-phenylethyl) pyrrole,

2- [2- (methyl-4-imidazolylmethylthio) ethylamino] -3-nitro-4-phenylpyrrole,

2- [2- (5-methyl-4-imidazolylmethyl! O) ethylamino] -3-nitro-4-n-butilpirrol,

2 - [(3-k] cyclopyrid-2-yl) methylthiolethylamirio-3-nitropyrrole and 2- (5-dimethylaminomethyl-2-furylmethylthio) ethylamine.

-1180082

Compounds of formula (I) according to the invention are prepared by reacting a compound of formula (Het) - (CH ₂ ) ₂ Y - where Y is -S (CH ₂ ) ₂ NH ₂ - with (2) with a compound of formula wherein X is a QSO group wherein Q is a lower alkyl or optionally substituted lower alkyl benzyl, phenyl or other cleavable group which can be substituted by an amine.

Preferably X is QSO, especially methylthio or benzylthio.

Intermediates of formula (2) wherein X is QSO are prepared according to the reaction scheme outlined in Scheme A). A compound of Formula (3) wherein E is Het- (CH ₂ ) -S- (CH ₂ ) ₂ NH- or QS and X ¹ is QS- or (if E is QS-) QSO- is a H 2 N-CH 2 CO R oxo compouind ³ or H 2 N ₂ CR ³ (oR ⁵⁾ ₂ or aminoacetállal aminoketállal formula wherein ^R5 is lower alkyl, is reacted.

When an aminoacetate or an aminoketal is used, the reaction is preferably carried out under neutral conditions, such as hot ethanol, and the product is cyclized under acidic conditions, such as by treatment with hydrogen chloride in a solvent (e.g., ether or lower alkanol), to afford (4). to give a compound of the formula: A compound of formula (4) wherein E is QS can be converted to a compound of formula (2) wherein X is a QSO group by treatment with equivalent hydrogen peroxide.

The compounds of formula (1) block the H ₂ -receptors, i.e., they inhibit the biological actions of histamine that are not inhibited by "antihistamines" such as mepiramine but are inhibited by burimamide. For example, these compounds inhibit histamine-stimulated gastric acid secretion from the gastric cavity of urethane anesthetized rats at doses ranging from 0.5 to 256 micromoles / kg when administered intravenously. The H ₂ -histanine receptor antagonist activity of these compounds is also demonstrated by their ability to inhibit other effects of histamine that are not mediated by the β-histamine receptors. For example, they inhibit the effect of histamine on isolated guinea-pig heart and isolated rat uterus. These agents also inhibit the basal secretion of gastric acid and the stimulation of pentagastrin or food stimulated secretion. In conventional experiments, such as measuring the blood pressure of an anesthetized cat, these compounds inhibit the vasodilating effect of histamine at intravenous doses of 0.5 to 256 micromoles / kg. The activity of these agents is shown by 50% inhibition of gastric acid secretion in anesthetized rats and also by 50% inhibition of histamine-induced taehycardia in isolated guinea-pig atria (less than 10 moles).

For therapeutic use, the pharmacologically active compounds will normally be administered in the form of a pharmaceutical composition comprising at least one such compound in association with a carrier, such as an acid addition salt with a free base or pharmaceutically acceptable salt, such as an acid addition salt. Such two addition salts formed with hydrochloric, hydrobromic, hydriodic, sulfuric and maleic acids, which may be prepared by conventional methods from an appropriate base, such as va the base is ^one which is treated with an acid in a lower alkanol or by using ion exchange resin to the desired salts are prepared or they may be given directly to the base or from another addition salt.

The pharmaceutical carrier may be solid or liquid. Solid carriers include lactose, terra alba, sucrose, talc, gelatin, agar, pectin, acacia, magnesium stearate and stearic acid. Liquid carriers include, for example, syrup, peanut oil, olive oil and water.

When solid carriers are employed, the preparation may take the form of tablets, capsules, pills, or lozenges. The amount of solid carrier in a unit dose will generally range from 25 mg to 300 mg. In cases where a liquid carrier is used, it can be a syrup, emulsion, soft gelatin capsule, sterile injectable liquid such as an ampoule, and the aqueous cut into ^r in a non-aqueous liquid suspension. The pharmaceutical compositions may be prepared by conventional methods, such as mixing, granulating and compression, or by dissolving the active ingredients to form the desired composition.

The active ingredients are preferably formulated in unit dosage form, each unit dose containing sufficient active ingredient to block the H ₂ histamine receptors. Each unit dose preferably contains from about 50 mg to about 250 mg.

The H ₂ -bistanane receptors can be blocked by administration of the active compounds of formula (1) in the form of pharmaceutical compositions.

Preferably, the drug-containing pharmaceutical compositions are administered 1 to 6 times daily. The daily dose will generally vary from about 150 mg to about 1500 mg of active ingredient.

Λ the product is administered orally or parenterally.

The following examples illustrate the process according to the invention. Temperatures are given in degrees Celsius.

Example 1 (a) (i) A solution of 8 g (0.06 mol) of aminoacetaldehyde deacetal and 10 g (0.06 mol) of 1-nitro-2,2-bis-methylthioethylene in 100 ml of ethanol is refluxed for 20 hours. boil. The solvent was removed in vacuo and the residue was chromatographed on a silica gel column. Elution was carried out with carbon tetrachloride / chloroform (7: 3) and the product was crystallized from propan-2-ol. 8.7 g of 1-nitro-2-methylthio-2- (2,2-diethoxyethylamino) ethylene are thus obtained in 58% yield.

73-73.5 °.

(ii) A solution of 11 g (0.08 mol) of aminoacetaldehyde diacetal and 15 g (0.08 mol) of 1-nitro-2-methylthio-2-methylsulfinylethylene in 200 ml of methanol is stirred for 2 1/2 hours at room temperature. The solvent was removed in vacuo and the resulting oily residue was triturated with propan-2-ol. Thus 9.8

-2180082 g of 1-nitro-2-methylthio-2- (2,2-diethoxyethylainino) ethylene were obtained in 49% yield.

Mp 72-74 °.

(b) A solution of 9.7 g (0.04 mol) of 1-nitro-2-methylthio-2- (2,2-diethoxyethylamino) ethylene in 250 ml of dry ether and 5 to 10 'of anhydrous hydrogen chloride gas is passed through with stirring. The resulting mixture was made basic by pouring into 300 ml of potassium carbonate solution. The mixture was filtered to give a yellow solid. The aqueous phase of the filtrate was separated and extracted with ether (2 x 150 mL). The combined ethereal solutions were evaporated. The residue and the former solid, which was collected by filtration, were recrystallized from acetone-chloroform to give 2-methylthio-3-nitropyrrole (3.4 g, 54%).

Mp 212-213 °.

Analysis for C ₅ H ₆ N ₂ O ₂ S:

Found: C, 38.0; H, 3.8;

N, 17.7; S, 20.1%. Calculated: C, 38.0; H, 3.8;

N, 17.7; S (20.3%) (c) A solution of 2-methylthio-3-nitropyrrole (2.5 g, 0.016 mol) in glacial acetic acid (70 ml) and hydrogen peroxide (2 ml, 0.017 mol, 100 vol) was heated at 60 ° for 4 hours. . The peroxide was decomposed and the solvent removed in vacuo and the residue recrystallized from propan-2-ol. 2.3 g of 2-methylsulfinyl-3-nitropyrrole are thus obtained in 85% yield.

162-164 °.

Analysis for C ₅ H ₆ N ₂ O ₃ S:

Found: C, 34.45; H, 3.4;

N, 15.9; S, 18.3%. Calculated: C, 34.5; H, 3.5;

N, 16.1; S, 18.4%.

(d) A solution of 2 g (0.01 mol) of 2-methylsulfiryl, 3-nitropyrrole and 2 g (0.01 mol) of 2- (5-methyl-4-imidazolylmethylthio) ethylamine in 50 ml of methanol was refluxed for 7 days. heat while steaming to dry. The residue was chromatographed on a silica gel column, eluting with ethyl acetate. The eluate was evaporated to dryness and the residue was recrystallized from propan-2-ol. 0.96 g of 2- (2- (5-methyl-4-imidazolylmethylthio) ethylamino) -3-nitropyrrole is obtained in a yield of 31%.

Mp 161-162 °.

Analysis for C _U H, ₅ N ₅ O ₂ S:

found: C 46.9; H, 5.45; N 24.6; S, 11.0%; date: C 47.0; H, 5.4; N 24.9; S, 11.4%; Example 2 (a) 5.7 g (0.1 mole) powdered potassium hydroxide

To a solution of 1-nitro-2-methylthio-2-methylsulfinylethylene (9.3 g, 0.05 mol) in aminoacetone hydrochloride (5.6 g, 0.05 mol) in methanol (100 mL) was added portionwise and the mixture was heated to reflux. After heating for 5 minutes, the mixture was cooled and the solvent removed in vacuo, water was added to the residue and the resulting solid was recrystallized from chloroform-methanol-petroleum ether (1145) to give 1.45 g of 2-methylthio-3-nitro- 4-methylpyrrole was obtained in 16% yield.

Mp 216-216.5 °.

Analysis for C ₆ H ₃ N, O ₂ S:

Found: C, 41.9; H, 4.6;

N, 16.2; S, 18.8%;

Calculated: C, 41.85; H, 4.7;

N, 16.3; S 18.6% (b) Az 1 / c). In Example 1, 2-methylthio-3-nitropyrrole is replaced by an equivalent amount of 2-methylthio-3-mitro-4-methylpyrrole to give 2-methylsulfinyl-3-nitro-4-methylpyrrole in 82% yield. 161-162 ° (ethyl acetate).

Analysis for C ₆ H ₃ N ₂ O ₃ S

Found: C, 38.5; H, 4.4; N, 14.9; S, 16.9%. C, 38.3; H, 4.3; N, 14.9; S 17.0% (c) Az 1 / d). In Example 1, 2-methylsulfinyl-3-nitro-pyrrole is replaced by 2-methylsulfinyl-3-nitro-4-methylpyrrole in equivalent amount and thus 25% yield of 2- [2- (5-methyl-4-imidazolylmethylthio) -ethylamino] - 3-nitro-4-methylpyrrole is obtained.

0m. 172 °.

Analysis for C _{V 2} H _1: NO ₃ S

Found: C, 48.95; H, 6.8; N, 23.8; S, 10.8%. C, 48.8; H, 5.8; N, 23.7; S 10.9%

Example I (a) A solution of 1.9 g (0.084 mol) of sodium lumoxide in 100 ml of methanol and 7.9 g (0.042 mol) of a solution of 1-amino-3-phenylpropan-2-one hydrochloride in 100 ml of methanol are stirred simultaneously. is added to a solution of 7.7 g (0.042 mol) of 1-nitro-2-methylthio-2-methylsulfinylethylene in methanol. The temperature is maintained at about 60 ° during the addition. Adding takes about 25 minutes. The solvent was then removed in vacuo and the residual dark red oil was chromatographed on a silica gel column. Elution was carried out with petroleum ether / ethyl acetate (7: 3) and the product recrystallized from the same mixture. This gives 2.95 g of 2-methylthio-3-nitro-4-benzoylirrole in 28.5% yield.

190-192,5 °.

Found: C, 57.8; H, 4.83; N, 11.33; S, 12.6%. Calculated: C, 58.05; H, 4.9; N, 11.3; S 12.9% (b) Az 1 / c). In Example 1, 2-methylthio-3-nitro-pyrrole is replaced by 2-methylthio-3-nitro-4-benzylpyrrole in equivalent amounts to give 1.7 g of 2-methylsulfinyl-3-nitro-4-benzylpyrrole in 58% yield.

189-190 ° (ethyl acetate).

Analysis for C _r H ₁₂ N _{O 3} S Found Found: 'C, 54.3; H, 4.6; N, 10.7; S, 11.9%. H, 4.6; Ν '10.6; S 12.1% (c) Az 1 / d). In Example 1, 2-methylsulfinyl-3-nitropyrrole is replaced by an equivalent amount of 2-methylsulfinyl-2-nitro-4-benzylpyrrole to give 1.08 g of 1- [2- (3-methyl-4-imidazolylmethylthio) ethylamino] -3-nitro- 4-Money-pyrrole is obtained in 52% yield. Mp 192.5-193 °.

Analysis for C _{21 H} II Found NO% Found: C 58.6; H, 5.7; N, 18.9; S, 8.5%. C, 58.2; H, 5.7; N, 18.85; S 8.6%

Example 4 (a) 6.87 g (0.040 mol) of α-aminoacetophenone hydrochloride are mixed with 7.25 g (0.040 mol) of 1-nitro-2-methylthio-2-methylsulfinylethylene in 300 ml of anhydrous methanol and the mixture is heated to 60 °. Sodium methoxide (prepared from 0.92 g of sodium (0.080 grams) and 25 ml of methanol) was added dropwise with stirring over about 10 minutes. After the addition was complete, the mixture was stirred at 60 ° C for 1 hour and then precipitated. 5.66 g of 2-methylthio-3-nitro-4-phenylpyrrole are obtained.

M.p. 259-261 ° (dec.).

Analysis C H _{N la} O ₂ N ₂ S Found Found: C, 56.0: H, 4.3; N, 11.85; Calculated: C, 56.4; H4.3; N 12.0% (b) 3.00 g (0.013 mol) of 2-methylthio-3-nitro-4-phenylpyrrole are suspended in 200 ml of glacial acetic acid and 1.45 g (0.013 mol) of 30% hydrogen peroxide are added. The mixture was stirred at 80 ° for 5 hours, then evaporated to dryness and the solid residue crystallized from isopropanol. 2.52 g of 2-methylsulfinyl-3-nitro-4-phenylpolyte are thus obtained. 197 DEG (dec).

Analysis for C _u H ₁₀ N ₂ O ₃ S Calcd Found: C, 52.5; H, 4.05; N, 11.3%. Calculated: C, 52.8; H, 4.0; N, 11.2% (c) 2-Methylsulfinyl-3-nitro-4-phenylpyrrol; 2.0 g (0.008 mol) was partially dissolved in 150 ml of ethanol and a solution of 1.37 g (0.008 mol) of 2- (5-methyl-4-imidazolylmethylthio) ethylamine in a small amount of ethanol was added. The mixture was heated at reflux for 7 days, then concentrated and chromatographed on a silica gel column. The desired product is obtained by elution with ethyl acetate. The crude solid was recrystallized from 2-propanol to give 2- [2- (5-methyl-4-imidazolylmethylthio) ethyl] amino-3-nitro-4-phenylpyrrole (0.46 g).

Mp 182-184 °.

Analysis for C ₁₇ H ₁₉ N ₅ O ₂ S Found: C, 56.8; H, 5.5; N, 19.8; S, 8.7%. C, 57.1; II, 5.4; N, 19.6; S 9.0%

Example 5 (a) In Example 3a, 1-amino-3-phenylpropan-2-one hydrochloride is replaced by an equivalent amount of 1-amino-4-phenylbutan-2-one hydrochloride to give 2-methylthio-3-r. yielding itro-4- (2-phenylethyl) pyrrole.

Mp 198-200 °.

(b) In Fig. 1 / c). In Example 1, 2-methylthio-3-nitro-pyrrole is replaced by an equivalent amount of 2-methylthio-3-nitro-4- (2-phenylethyl) pyrrole to give 2-methylsulfinyl-3-nitro-4- (2-phenylethyl) pyrrole. % yield.

Mp 171.5-173 °.

(c) As in 1 / d. In Example 1, 2-methylsulfinyl-3-nitro-pyrrole is replaced by an equivalent amount of 2-methylsulfinyl-3-nitro-4- (2-phenylethyl) -pyrrol to give 2- [2- (5-methyl-4-imidazolylmethylthio) -ethylamino] -3-nitro-4 (2-phenylethyl) pyrrole was obtained in a yield of 31%.

Mp 186-187 °.

f. EXAMPLE 1 (i) 39.6 g of sodium hydride (in the stock of a 50% oily solution) was added portionwise to a solution of 107.5 g of ethyl acetate in dry ether under a nitrogen atmosphere. 100 g of valeryl chloride were then added dropwise to the suspension with stirring over 2 1/2 hours, and the mixture was poured into 509 ml of distilled water. The ether layer was separated and dried and the ether removed. This gave 142 g of ethyl valeryl acetate acetate as a yellow oil.

(ii) A solution of 41.3 g of sodium nitrite in water is slowly added to a solution of 118.7 g of ethyl 2-valerylacetoacetate in 100 ml of acetic acid under cooling and the temperature is kept below 10 °. Then, 100 g of ice was added, followed by 105.0 g of acetic anhydride. A total of 65.4 g of zinc powder was added per portion and the temperature was kept under stirring below 20 ° until the reaction was complete. The mixture was then allowed to stand overnight at room temperature and then filtered. The solid was washed with chloroform and the filtrate was extracted with chloroform. The chloroform extracts were washed with sodium carbonate solution and dried. The solvent was removed in vacuo and the residue was purified by silica gel column chromatography. Elution with petroleum ether (b.p. 60-80 °) -ethylacetate gave 13.5 g of ethyl 2-acetamido-3-oxoheptanoate which was used without further purification.

(iii) Hydrolysis of 10.4 g of ethyl 2-acetamido-3-oxoheptanoate by heating with 80 ml of 50% hydrochloric acid for 9 hours. The mixture was evaporated to dryness to give 5.8 g of -amino-2-hexanone hydrochloride as a dark red oil.

(iv) Dissolve 5.8 g of l-amino-2-hexanone hydrochloride in 100 ml of methanol and add 6.8 g of the solution.

Mix with a solution of 1-methylthio-1-methylsulfinyl-2-nitroethylene in 100 mL of methanol. thereafter

Methanolic sodium methovide (1.7 g) in sodium hydroxide solution was added dropwise over 2 hours at 60 ° C and the whole was evaporated to dryness. The residue was triturated with water and the solid was collected by filtration and dried. 3.9 g of 2-methylthio-3-nitro-4-n-butylpyrrole are thus obtained.

(v) 3.7 g of 2-methylthio-3-nitro-4-n-butylpyrrole are suspended in 50 ml of glacial acetic acid and 1.62 g of 30% hydrogen peroxide are added. The mixture was heated at 80 ° for 7 hours and then concentrated to a brown oil. The crude product was purified by silica gel column chromatography eluting with benzene and chloroform. This gives an oil which crystallizes upon standing. The crystalline material was recrystallized from 2-propanol to give 1.6 g of 2-methylsulfinyl-3-nitro-4-n-butylpyrrole.

133-134 °.

(vi) 2.78 g of 2-methylsulfinyl-3-nitro-4-n-butylpyrrole are dissolved in ethanol and 2.08 g are added.

Of 2- (5-methyl-4-imidazolylmethylthio) ethylamine in a total of 100 ml of ethanol. The mixture was heated at reflux for 9 days and then the solution was evaporated to dryness. The residue was subjected to silica gel column chromatography (4180082) eluting with chloroform and ethyl acetate. 0.65 g of crude product is obtained in the form of a brown oil. The crude product was dissolved in isopropanol (30 mL) and treated with maleic acid (0.5 g) in 2-propanol. The mixture was heated on a water bath for a few minutes and then allowed to cool to give 0.19 g of 2- [2- (5-methyl-4-imidazolylmethylthio) ethyl) amino-3-nitro-4-n-butylpyrrole maleate as sparkling crystals. .

94-95 °.

Example 7

1.22 g of 2- (3-chloro-2-pyridylmethylthio) ethylamine dihydrobromide are neutralized by reaction with aqueous sodium hydroxide solution and the free base is extracted with chloroform. The solvent was evaporated, the base was dissolved in ethanol and the solution was added to a solution of 0.59 g of 2-methylsulfinyl-3-nitropyrrole in ethanol. The mixture was heated at reflux for 10 days and then evaporated to dryness. The residue was chromatographed on a silica gel column, eluting with chloroform. The crude product was recrystallized from 2-propanol to give 2- [2- (3-chloro-2-pyridylmethylthio) ethylamino] -3-nitropyrrole.

144-147 ° (dec.).

Analysis for C ₁₂ H ₁₃ N, O ₂ SC ₁ Found: C, 45.98; H, 4.20; N, 17.57. Calculated: C, 46.08; H 4.19; N, 17.91%

Example 8 A solution of g (0.014 mol) of 2- (5-dimethylaminomethyl-2-furylmethylthio) -ethylamine and 2 g (0.011 mol) of 2-methylsulfinyl-3-nitropyrrole in 50 ml of ethanol was heated at reflux for 7 days and then evaporated to dryness. The residue was purified on a silica gel column eluting with ethyl acetate-petroleum ether (b.p. 60-80 ° C). This gives 2- [2- (5-dimethylaminomethyl-2-furylmethylthio) ethylamino] 3-nitropyrrole.

Claims (7)

Patent claims A process for the preparation of a nitro compound of formula (I) wherein: Seven 5-methylimidazolyl, 3-chloro-2-pyridyl or 5-dimethylaminomethyl 1-2-furones It is ³ hydrogen, lower alkyl, phenyl, benzyl or phenylethyl, Characterized in that a compound of the formula Het- (CH ₂ ) Y wherein Sev is as defined above and Y is a -S (CH ₂ ) ₂ NH ₂ group is reacted with a compound of the general formula (2) wherein X is a QSO- a group where Q can be cleaved by an amine 10 interchangeable groups, preferably benzyl or phenyl substituted with lower allyl or optionally lower alkyl. 2. A process according to claim 1 for the preparation of 2- [2- (5-methyl-4-imidazolylmethylthio) ethylamino] -3-nitro-4-methylpyrrole, wherein the starting materials are 2-methylsulfonyl-3 -nitro-4-methylpyrrole and 2- (5-methyl-4-imidazolylmethylthio) ethylamine. The method of claim 1, which is an embodiment 20 ways (2- [2- (5-methyl- 4-imidazolylmethylthio) ethylamiro] -3-nitro-4-benzylpyrrole, characterized in that 2-methylsulfonyl-3-nitro-4-benzylpyrrole and 2- (5-methyl-4-imidazolylmethylthio) ethylamine are used as starting materials . 4. A process according to claim 1 for the preparation of 2- [2- (5-methyl-4-imidazolylmethylthio) ethylamiro] -3-nitro-4- (2-phenylethyl) pyrrole as starting materials. 2-Methylsulfinyl-3-nitro-4- (phenylethyl) pyrrole and 2- (5-methyl-430-imidazolylmethylthio) ethylamine were used. 5. A process according to claim 1 for the preparation of 2- [2- (5-methyl-4-imidazolylmethylthio) ethylamiro] -3-nitro-4-phenylpyrrole, wherein the starting materials are 2-methylsulfonyl-3-yl. -nitro-4-phenylpyrrole and 2- (5-methyl-4-imidazolyl triethylthio) ethylamine are used. 6. A process according to claim 1 for the preparation of 2- [2- (5-methyl-4-imidazolylmethylthio) ethylamiro] -3-nitro-4-n-butylpyrrole, wherein the starting materials are 2-methylsulfuryl. -3-nitro-4-n-butylpyrrole and 2- (5-methyl-4-imidazolylmethylthio) ethylamine are used. 7. A process according to claim 1 for the preparation of 2 - [(3-chloropyrid-2-yl) methylthio] ethylamino-345 ritropyrrole, wherein the starting materials are 2- (3-chloro-2-pyridylmethylthio). ethylammonium hydrobromide and 2-methylsulfinyl-3-nitropyrrole are used.