CS210685B2 - Manufacturing process of 2-nitroaminopyrimidones - Google Patents

Description

(54) A method for producing 2-nitroaminopyrimidones

The present invention relates to a process for the preparation of novel 2-nitroaminopyrimidones useful as starting materials for the preparation of 2-aminopyrimidones which are effective as H ₂ -amine histamine antagonists.

A process for the production of the aforementioned 2-aminopyrimidones by a preferred novel process using the novel 2-nitroaminopyrimidones produced by the process of the present invention is described and protected in our related Czechoslovak patent specification 210,684 (PV 2440-79).

Accordingly, the present invention provides a process for the preparation of 2-nitroaminopyrimidones of formula I,

in which

B represents a pyrldyl radical optionally substituted by one or more C 1 -C 4 alkyl or C 1 -C 4 alkoxy groups, a furyl radical, a naphthyl radical, a 6- (2,3-dihydro-1,4-benzodioxinyl) radical A 5- (1,3-benzodioxolyl) radical or a phenyl radical optionally substituted by one or more C 1 -C 4 alkoxy groups, characterized in that the β-οχοester of the general formula II,

H

AND

O = C \

HC-CH ₂ B

RO ₂ C in which

R is C 1 -C 4 alkyl, reacted with nitroguanidine.

The above-mentioned C 1 -C 4 alkyl and alkoxy groups may be straight or branched. Examples of suitable alkyl groups include methyl, ethyl, 1-propyl and 2-propyl, and examples of suitable alkoxy groups include methoxy, ethoxy, 1-propoxy, 2,10685, and 2-propoxy. Particular B radicals include 2-furyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 6-methyl-3-pyridyl, 5,6-dimethyl-3-pyridyl, 6-methoxy-3- pyridyl, 2-methoxy-4-pyridyl and 4-methoxy-2-pyridyl.

Examples of specific substituted phenyl groups for B are 3-methoxyphenyl, 4-methoxyphenyl, 3,4-dimethoxyphenyl and 3,4,5-trimethoxyphenyl.

The compounds of formula (I) above are depicted and described as 4-pyrimidone derivatives, but these derivatives are in equilibrium with the corresponding tautomeric 6-pyrimidones and the pyrimidine ring may also exist in the following tautomeric forms:

S \ n ₂ n nh ₂

The method of the invention is

can be described by the following reaction by the scheme: H \ O - C \ £ Η ₂ Β HC-CH-B / νο, νη ro ₂ c of (II) (1)

The reaction according to the invention is preferably carried out in the presence of a base, for example an alkali metal hydroxide or lower alkoxide, sodium hydride or a quaternary ammonium hydroxide, such as benzyltrimethylammonium hydroxide. The base used is preferably sodium hydroxide, sodium ethoxide or sodium methoxide, preferably 2 mol equivalents of these bases. The reaction is preferably carried out in a lower alkanol such as methanol, ethanol or 1-propanol, in a mixture of water and a lower alkanol or in dimethylformamide.

Preferably, the reaction is carried out at elevated temperature, for example at reflux, but any temperature at which the reaction proceeds at an acceptable rate may be used. Nitroguanidine is generally marketed in the wet state (containing, for example, 17 to 25% by weight of water) and can be used in the wet or dry state by reaction. Particularly preferred are those compounds of formula I wherein B is 6-methyl-3 In general, the products of formula (I) can be easily purified by recrystallization and are stable when stored at room temperature.

The β-oxoesters of formula II above may generally be prepared by formylation of an ester of formula

BCH ₂ —CH ₂ CO ₂ R is a lower alkyl formate such as ethyl formate in the presence of a strong base such as sodium hydride in 1,2-dimethoxyethane or tetrahydrofuran or sodium in ether. Preferably at least 1.5 mol equivalents of ethyl formate are used in this reaction. Preferably, about 2 mol equivalents of sodium hydride are used. The β-oxoesters of formula (II) may be used to react with nitraguanidine in unpurified form, or in some cases may be isolated and used as crystalline solids.

The invention is illustrated by the following Examples and Preparations of Starting Materials, which are not intended to limit the scope of the invention in any way. In these examples and preparations, all temperatures are given in degrees Celsius.

EXAMPLE 1 (i) A mixture of 51.57 g of 6-methylpyridine-3-carboxaldehyde, 44.30 g of maleic acid, 6 ml of piperidine and 300 ml of pyridine was stirred at 100 DEG C. for 3 hours and then allowed to cool. The reaction mixture is evaporated to dryness, water is added to the residue, the solid material is filtered off and recrystallized from ethanol / acetic acid to give 41.25 g of 3- (6-methyl-4-pyridyl) acrylic acid, m.p. 213.5. to 215.5 °.

(iij A mixture of 50.70 g of 3- (6-methyl-3-pyridyl-acrylic acid), 350 ml of dry ethanol and 25 ml of concentrated sulfuric acid was refluxed for 18 hours, after which time ethanol (ca. 250 ml) was evaporated. The residue was poured into a mixture of ice and aqueous ammonia, the resulting mixture was extracted with ether, the ether extracts washed with water and evaporated to an oily residue which crystallized on standing to give ethyl 3- (6-methyl-3-pyridyl) acrylate at a temperature. mp 36-37 °.

(iii) 60.36 g of ethyl 3- (6-methyl-3-pyridyl acrylate) in ethanol is hydrogenated at 35 ° at 35 mm Hg in the presence of 1.0 g of 10% palladium on carbon catalyst. the filtrate was evaporated to give ethyl 3- (6-methyl-3-pyridyl) propionate as an oil.

(iv) To a suspension of 4.07 g of sodium hydride as a 50% dispersion in oil in 24 ml of 1,2-dimethoxyethane, 1.31 g of ethyl 3- (6-methyl-) was added dropwise while maintaining the temperature at 0 °. 3-pyridyl) propionate and 7.43 g ethyl formate. The mixture was allowed to warm to room temperature, stirred overnight, then poured into 300 g of ice water. The aqueous mixture is extracted with ether, the aqueous phase is acidified to pH 5.4 with hydrochloric acid and the precipitated solid is filtered off. 10.5 g (70%) of ethyl 2-formyl-3- (6-methyl-3-pyridyl) propionate are obtained, m.p. 142-144 °.

EXAMPLE 2 (i) A mixture of 111 g of ethyl formate and 108 g of 2-butanone is added dropwise to 72 g of a 50% w / w dispersion of sodium hydride in oil, in dry 1,2-dimethoxyethane. The mixture was allowed to stand overnight, then ether (800 ml) was added and the solid (101 g) was filtered off. To this solid was added 69.5 g of cyanacetamide, piperidine acetate (prepared by adding piperidine to 7 mL of acetic acid and 18 mL of water until the reaction was basic) and 400 mL of water, heated to reflux for 2 hours, allowed to stand at room temperature. cool and acidify with acetic acid. The precipitated solid product was recrystallized from aqueous ethanol

43.5 g of 3-cyano-5,6-dimethyl-2-hydroxypyridine.

(ii) A vigorously stirred mixture of 3-cyano-5,6-dimethyl-2-hydroxypyridine (42 g) and phosphorus pentachloride (81 g) was heated at 140-160 ° for 2 hours, then the phosphoryl chloride was distilled off under reduced pressure. of water with ice. The pH was adjusted to 7 with aqueous sodium hydroxide and the mixture was extracted with ether. The ether extracts are evaporated to an oily residue which, after crystallization from a mixture of ether and petroleum ether (b.p. 60-80 °), yields 25.3 g of 2-chloro-3-cyano-5,6-dimethylpyridine, m.p. 83-87 °.

(iii) A mixture of 21.5 g of 2-chloro-3-cyano-5,6-dimethylpyridine, 24.0 g of semicarbazide hydro-chloride, 42.3 g of sodium acetate, 225 ml of water and 475 ml of methanol is hydrogenated at 50 psi. at 50 ° in the presence of g Raney nickel catalyst. The reaction mixture is added to 750 ml of water, filtered, the filtered solid is suspended in 130 ml of water and 70 ml of concentrated hydrochloric acid are added. The mixture was heated at 100 ° for 1 hour, then 120 ml of 40% (w / w) formalin was added thereto, and the resulting mixture was heated at 100 ° for a further 0.5 hours and then allowed to cool. After addition of 95 g of sodium acetate and 250 ml of water, the mixture is extracted with ether, the extracts are washed with 5% aqueous potassium carbonate and evaporated. 13.24 g (60%) of 2-chloro-5,6-dimethyl-3-pyridinecarboxaldehyde, melting at 69-70 °, are obtained.

(iv) A mixture of 16.85 g of 2-chloro-5,6-dimethyl-3-pyridinecarboxaldehyde, 11.45 g of malonic acid, 10 ml of piperidine and 100 ml of pyridine was heated at reflux for 1 hour, then evaporated to reflux. oily residue. The oily material was dissolved in sodium hydroxide solution, extracted with chloroform, the remaining aqueous phase was acidified with hydrochloric acid and extracted with chloroform. These second chloroform extracts were washed with water and evaporated to give 18.3 g (87%) of 3- (2-chloro-5,6-dimethyl-3-pyridyl) acrylic acid, melting at 150-158 °. This acid is esterified using ethanol and sulfuric acid to give the corresponding ethyl ester, m.p. 85-88 °.

(v) 32.7 g of the above ethyl ester are hydrogenated in 500 ml of ethanol in the presence of 3 g of 5% palladium on carbon catalyst at a temperature of 25-30 ° at a pressure of 50 psi. The reaction mixture was filtered and the filtrate was evaporated to an oily residue which was partitioned between chloroform and 2N hydrochloric acid. The aqueous phase was basified with aqueous sodium hydroxide solution, extracted with chloroform, and the chloroform extracts were evaporated. 21.8 g (80%) of oily ethyl 3- (5,6-dimethyl-3-pyridyl) propionate are obtained.

(vi) Ethyl 3- (5,6-dimethyl-3-pyridyl) propionate was reacted with ethyl formate and sodium hydride in dimethoxyethane at room temperature. Ethyl 3- (5,6-dimethyl-3-pyridyl) -2-formylpropionate is obtained, m.p. 148-149 °. Preparation 3 (i) To a solution of sodium methoxide (prepared from 20.8 g of sodium) in 285 ml of methanol was added 115.5 g of 2-chloro-4-cyanopyridine in 850 ml of a mixture of equal parts of methanol and dioxane. The resulting mixture was refluxed for 2.5 hours, allowed to cool, filtered, 200 ml of distillate evaporated from the filtrate and 400 ml of water added to the residue. Filtration of the precipitated product gave 57.2 g (51%) of 2-methoxy-4-cyanopyridine, m.p. 93-95.5 °.

(il) A mixture of 57.2 g of 2-methoxy-4-cyanopyri210685 dinine, 71.24 g of semicarbazide hydrochloride, 69.86 g of sodium acetate, 1200 ml of ethanol and 370 ml of water was added in the presence of 1.0 g of Raney-nickel as The catalyst is hydrogenated at 50 psi. The reaction mixture was evaporated to a volume of 450 mL, 900 mL of water was added, the mixture was allowed to stand overnight at 0 °, then filtered. The solid material was washed with water, dissolved in 950 ml of 10% hydrochloric acid, 420 ml of a 36% w / v formaldehyde solution was added, the resulting mixture was heated for 30 minutes, then allowed to cool and added to a solution of 290 g of sodium acetate. in 840 ml of water. The mixture was extracted with ether, the extracts were combined, washed successively with aqueous potassium carbonate solution and water, dried and evaporated. There were obtained 20.53 g ^(35;%) of 2-methoxypyridine-4-carboxaldehyde, mp 33-35 °. A sample of the product melts after recrystallization from petroleum ether at 33-367 (iiij Condensation of 2-methoxypyridine-4-carboxaldehyde with malonic acid followed by esterification and hydrogenation at 344 kPa and formylation of the product with ethyl formate and sodium hydride affords ethyl 2-forms 1-3 - (2-methoxy-4-pyridyl) propionate as an oil.

Preparation 4.

Replacement of 2-methoxypyridine-4-carboxaldehyde in the work-up procedure

3,4-Methoxypyridine-2-carboxaldehyde gives oily ethyl 3- (4-methoxy-2-pyridyl) propionate, which formylation affords ethyl 2-formyl-3- (4-methoxy-2-pyridylmethyl) pyrimidine.

PREPARATION 5 (i) A mixture of 2-methoxy-5-cyanopyridine (61.26 g), semicarbazide hydrochloride (76.4 g), sodium acetate (74.92 g), ethanol (1300 ml) and water (400 ml) in the presence of 1.0 g The Raney-Nickel catalyst is hydrogenated at 50 psi. The reaction mixture was evaporated to a volume of 500 mL, 1000 mL of water was added, the resulting mixture was allowed to stand overnight at 0 °, then filtered. The solid material was washed with water, dissolved in 1000 ml of 10% hydrochloric acid, 450 ml of a 36% w / v formaldehyde solution was added, the mixture was heated for 15 minutes, then allowed to cool and added to the solution.

298.5 g sodium acetate in 900 ml water. The resulting mixture was extracted three times with 500 ml of ether each time, the combined extracts were washed successively with aqueous potassium carbonate solution and water, dried and evaporated. 31.5 g (50%) of 6-methoxypyridine-3-carboxaldehyde, melting at 48 to 497, are obtained. (Ii) A mixture of 2.34 g of 6-methoxypyridine-3-carboxaldehyde, 4.51 g of malonic acid monoethyl ester, 12 ml of pyridine. and 6 drops of piperidine are heated at reflux for 5 hours, then evaporated to an oily residue. The oily material was partitioned between ether and dilute aqueous ammonia solution, the ether layer was separated and evaporated. The oily residue crystallized on standing to give 2.8 g (79%) of ethyl 3- (6-methoxy-3-pyridyl) acrylate, melting at 49-52 °.

(IIIi) 32.33 g of ethyl 3- (6-methoxy-3-pyridyl) acrylate in 160 ml of ethanol was hydrogenated at 40 DEG C. in the presence of 0.2 g of 5% palladium on carbon catalyst. The mixture was filtered and the filtrate was evaporated to give 32.7 g of ethyl 3- (6-methoxy-3-pyridyl) proplonate as an oil.

(iv) To a suspension of 9.38 g of sodium hydride (50% oil dispersion) in 50 ml of 1,2-dimethoxyethane cooled to -2 °, a mixture of 32.74 g of ethyl-3- ( 6-methoxy-3-pyridyl) proplonate and 17.22 g of ethyl formate. The reaction mixture was allowed to stand overnight at room temperature, then poured onto ice, extracted with ether, the aqueous phase was acidified to pH 5 with 2 N sulfuric acid and the precipitated oil was allowed to stand, crystallizing. 25.9 g (70%) of ethyl 2-formyl-3- (6-methoxy-3-pyridyl) propionate, melting at 91.5 to 94 °, is obtained. A sample of the product melts after recrystallization from ethanol at 93-94 °.

Preparation6

Ethyl 3- (2-furyl) propionate is reacted at room temperature with 1.1 equivalents of ethyl formate and 1.0 equivalents of sodium hydride in 1,2-dimethoxyethane. Oily ethyl 2-formyl-3- (2-furyl) propionate is obtained in 75% yield.

Preparation 7

A mixture of 100 g of ethyl 3- (3-methoxyphenyl) propionate and 37 g of ethyl formate is added dropwise with stirring at 0 ° to 11 g of sodium wire in 500 ml of ether. The reaction mixture was stirred at room temperature for 16 hours, then evaporated to dryness, the residue was dissolved in water, extracted with ether, the aqueous phase acidified to pH 4 with hydrochloric acid and extracted again with ether. Evaporation of the ether extract to dryness yielded 46.05 g of ethyl 2-formyl-3- (3-methoxyphenyl) propionate.

Preparation 8

Ethyl 3- (3,4,5-trimethoxyphenyl) propionate is reacted with ethyl formate and sodium hydride in 1,2-dimethoxyethane. In a yield of 44%, crude ethyl 2-formyl-3- (3,4,5-trimethoxyphenyl) propionate is obtained.

Preparation 9

2,3-dihydro-1,4-benzodioxine-6-carboxaldehyde (m.p. 41-43 °, prepared by re-210685 actions of 3,4-dihydroxybenzaldehyde with ethanedisulfonic acid dimethyl ester and potassium hydroxide) is condensed with monoethyl malonate in pyridine in the presence of piperidine catalyst. Ethyl 3- [6- (2,3-dihydro-1,4-benzodioxinyl)] acrylate, melting at 49-53 °, is obtained, which is reduced with hydrogen in the presence of palladium on carbon and reacted with ethyl formate. and sodium hydride in 1,2-dimethoxyethane. There was thus obtained oily ethyl 2-formyl-3- [6- (2,3-dihydro-1,4-benzodioxinyl) propionate.

Preparation 10

To a suspension of 4.43 g of sodium hydride (57% dispersion in oil) in 1,2-dimethoxyethane was added a mixture of 18.01 g of ethyl 3- (1-naphthyl) propionate and 8.88 g of ethyl formate under stirring at 5 °. . The mixture was allowed to warm to room temperature, 300 mL of water was added, the mixture was extracted with chloroform, the aqueous phase acidified to pH 4 with hydrochloric acid, and extracted with ether. Evaporation of the ether extracts yielded 16.05 g of oily ethyl 2-formyl-3- (1-naphthyl) propionate.

Example 1

1.15 g of sodium are dissolved in 50 ml of methanol and added to the cooled solution

4.7 g of nitroguanidine. The mixture was heated at reflux for 45 minutes, then 9.3 g of ethyl 2-formyl-3- (3-pyridyl) propionate was added portionwise, and the resulting mixture was heated at reflux for 45 hours. evaporate to dryness. Water was added to the residue, the mixture was extracted with chloroform, the remaining aqueous phase was acidified to pH 5 with acetic acid, the precipitated solid product was filtered off and washed after drying. Yield 38%, 2-nitroamino-5- (3-pyridylmethyl) -4-pyrimidone, m.p.

Example 2

To a solution of sodium methoxide (prepared from 0.161 g of sodium) in 20 ml of methanol is added with stirring a solution of 1.55 g of ethyl 2-formyl-3- (6-methyl-3-pyridyl) propionate in 20 ml of methanol, then added 0.73 g of dried nitroguanidine, the resulting mixture was heated to reflux overnight and then evaporated to dryness. The residue is dissolved in 50 ml of water, the solution is extracted with chloroform and the aqueous phase is acidified to pH 5 with acetic acid. The precipitated solid is filtered off and recrystallized from methanol / acetic acid to give 0.5 g (27%) of 2-nitroamino- 5- (6-methyl-3-pyridylmethyl) -4-pyrimidone, m.p.

Example 3

To a solution of sodium methoxide (prepared from 1.45 g of sodium) in 65 ml of dry methanol was added 6.05 g of nitroguanidine, and the mixture was heated at reflux for 0.75 hours, then 14.3 g of ethyl ether were added. 3- (5,6-dimethyl-3-pyridyl) -2-formylpropionate, the resulting mixture was heated under reflux for 40 hours and then evaporated to dryness. 40 ml of water were added to the residue and the mixture was extracted with chloroform. The aqueous phase is acidified to pH 6 with hydrochloric acid, the precipitated solid product is filtered off and recrystallized from a mixture of dimethylformamide and ethanol. 5- (5,6-Dimethyl-3-pyridylmethyl) -2-nitroamino-4-pyrimidone is obtained, m.p. Example 4

Using the procedure described in Example 3, nitroguanidine was reacted with sodium ethoxide and ethyl 3- (4-methoxy-2-pyridyl) propionate to give 2-nitroamino-5- (4-methoxy-3-pyridylmethyl) pyrimidone, melting after crystallization from a mixture of ethanol and acetic acid with decomposition at 196-198 °.

Example 5

To a solution of sodium methoxide (prepared from 1.15 g of sodium) in 50 ml of methanol was added 4.7 g of nitroguanidine, the mixture was heated under reflux for 45 minutes, then 10.7 g of ethyl-2-formyl was added. Of 3- (6-methoxy-3-pyridyl) propionate, the resulting mixture was heated to reflux for 24 hours, evaporated to dryness, the residue dissolved in water and extracted with chloroform. pH 5 and the precipitated solid product was filtered to give 2-nitroamino-5- (6-methoxy-3-pyridylmethyl) -4-pyrimidone, m.p. 183.5-186 °.

Example 6

Using an analogous procedure to that of Example 5, reaction of nitroguanidine, sodium methoxide and ethyl 2-formyl-3- (2-methoxy-4-pyridyl) propionate affords 2-nitroamino-5- (2-methoxy-4-pyridylmethyl) - 4-pyrimidone, melting after crystallization from aqueous acetic acid at 194-195.5 °.

Example 7

To a mixture of 12.69 g (0.122 mol) nitroguanidine and sodium methoxide [prepared from 3.09 g (0.134 mol) sodium] in methanol was added 24.0 g (0.122 mol) ethyl-2-formyl-3- (2- The reaction mixture was heated to reflux for 18 hours with stirring, then evaporated to dryness, the residue was dissolved in water, acidified to pH 4 with 21% acetic acid, and the precipitated solid material was collected by filtration. 1 g (59%) of 2-nitroamino-5- (2-furylmethyl) -4-pyrimidone A sample of this product melts first from methanol / acetic acid and then from acetic acid at 183-184 ° after recrystallization.

Example 8

To a mixture of sodium methoxide (prepared from 1.15 g sodium) and 5.5 g nitroguanidine (25% humidity) in 250 ml methanol was added dropwise with stirring and boiling 10 g ethyl-2-formyl-3- (3-methoxyphenyl) of propionate, the resulting mixture was refluxed for 20 hours and then evaporated to dryness. The residue was dissolved in 100 mL of water, extracted with ether and the aqueous phase acidified to pH 4. The precipitated solid product was recrystallized from ethanol to give 3.41 g (29%) of 2-nitroamino-5- (3- methoxybenzyl) -4-pyrimidone melting at 178-179 °.

Example 9

The crude ethyl 2-formyl-3- (3,4,5-trimethoxyphenyl) propionate (7.41 g) was treated with 2.62 g of nitroguanidine and sodium methoxide in refluxing methanol for 40 hours. 2-Nitroamino-5- (3,4,5-trimethoxybenzyl) -4-pyrimidone is obtained in 13% yield.

Example 10

To sodium methoxide in methanol (prepared from 0.689 g of sodium and 50 ml of methanol) is added a solution of 7.5 g of ethyl 2-formyl-3- [5- (1,3-benzodioxolyl)] propionate in 20 ml of methanol, then 3.12 g of nitroguanidine are added with stirring, the reaction mixture is heated under reflux for 18 hours and then evaporated. The residue is dissolved in 200 ml of water, the solution is extracted with chloro685 form, the remaining aqueous phase is acidified to pH 5 with acetic acid and the precipitated white solid is filtered off. 4.08 g of 2-nitroamino-5- [5- (1,3-benzodioxolyl) methyl] -4-pyrimidone are obtained, m.p. 200-202 °. A sample of the product melts after recrystallization from aqueous acetic acid at 201.5 to 202.5 °. Example 11

To sodium methoxide (prepared from 2.76 g sodium) in 100 ml methanol was added 11.10 g nitroguanidine, the mixture was heated under reflux for 45 minutes, then 21.45 g ethyl-2-formyl- 3- [6- (2,3-dihydro-1,4-benzodioxinyl)] propionate, the resulting mixture was heated under reflux for 18 hours and then evaporated to dryness. The residue was dissolved in water and extracted with chloroform, The remaining aqueous phase was acidified to pH 5 with acetic acid and the precipitated solid was filtered to give 14.2 g (58%) of 2-nitroamino-5- [6- (2,3-dihydro-1,4-benzodioxinyl) methyl 194 DEG-197 DEG C. A sample of the product melts after recrystallization from acetic acid at 207 DEG-209 DEG.

Example 12

To a solution of sodium methoxide (prepared from 2.22 g of sodium) in 100 ml of methanol was added 9.10 g of nitroguanidine, the mixture was heated under reflux for 45 minutes, and 16.05 g of ethyl-2-formyl- was added. 3- (1-naphthyl) propionate, the resulting mixture was heated under reflux for 20 hours and then evaporated to dryness. The residue is taken up in water, the mixture is extracted with chloroform, the remaining aqueous phase is acidified to pH 4 with acetic acid and the precipitated solid product is recrystallized from acetic acid. 2-Nitroamino-5- (1-naphthylmethyl) -4-pyrimidone, m.p. 226 DEG-227 DEG, is obtained.

Claims (3)

Subject A process for the preparation of 2-nitroaminopyrimidones B is a pyridyl radical optionally substituted by one or more C 1 -C 4 alkyl or C 1 -C 4 alkoxy, furyl, naphthyl, 6- (2,3-dihydroxy-1,4-benzodioxinyl) radicals, - (1,3-benzodioxolyl or phenyl) optionally substituted by one or more C 1 -C 4 alkoxy groups, characterized in that the β-oxoester of the general formula (II), H I o = c \ _HC-CH2 B (II) / ro ₂ c in which R is C 1 -C 4 alkyl, reacted with nitroguanidine. 2. A process according to claim 1 wherein the reaction is carried out in the presence of a base. 3. A process according to claim 2 wherein the reaction is carried out with sodium hydroxide, sodium methoxide ethoxide.