DK156723B - Process for preparing 2-alkyl-4-amino-5- aminomethylpyrimidines - Google Patents

Description

DK 156723B

The present invention relates to a particular process for the preparation of 2-alkyl-4-amino-5-aminomethylpyrimidines.

It is known that 2-alkyl-4-amino-5-aminomethylpyrimidines are important intermediates for the synthesis of vitamin Bj and its analogs 5 (Encyclopedia of Chemical Technology, Second Edition, vol. 20, 173 (1969), John Wiley & Sons, Inc.).

For example, as processes for the preparation of 2-alkyl-4-amino-5-amino-methylpyrimidines, there has been known so far a method by which a 2-alkyl-4-amino-5-cyanopyrimidine is reduced (Yakugaku 10 Zassi ( Journal of Pharmaceutics), Japan, 21 »977 (1953), JACS 66 876 (1944), and a process of hydrolyzing a 2-alkyl-4-amino-5-acetamomethylpyrimidine (Chem. Ber. 106,893 (1973) ).

From US-A-4,152,353, it is known to prepare amines by reacting aldehydes with ammonia and hydrogen in the presence of a hydrogenation catalyst, optionally in an inert solvent. The hydrogenation catalyst is composed of nickel and copper as well as iron, zinc and / or zirconium as the third component. The amount of catalyst used is 0.1 to 20% by weight of the starting material and the molar ratio of ammonia to aldehyde is 1: 1 to 100: 1, while the molar ratio of hydrogen to 20 aldehyde can be 1: 1 to 20: 1. The reaction temperature is between 75 ° C and 250 ° C.

The present invention aims to provide a process for the preparation of 2-alkyl-4-amino-5-aminomethylpyrimidines which yields better yields than the known processes. This purpose is fulfilled by the method of claim 1.

The 2-alkyl-4-amino-5-formylpyrimidine used as the starting material has the following structural formula:

N / ScHO

wherein R represents a lower alkyl group having 1 to 5 carbon atoms, such as methyl, ethyl, propyl and butyl.

The starting material can be easily synthesized e.g. by hydrolyzing a 2-alkyl-4-amino-5-dialkoxy-methylpyrimidine in the presence of an acid. The 2-alkyl-4-amino-5-formylpyrimidine used as a starting material can also be used in the form of a site with a mineral acid, such as sulfuric acid, nitric acid, hydrochloric acid or phosphoric acid.

DK 156723 B

2

The reduction catalyst is selected from palladium, platinum, rhodium, ruthenium, nickel, cobalt, iron, copper and chromium. These metals are usually used in the form of the metal itself. However, they can also be used in the form of a site, an oxide or an alloy. Furthermore, nickel may be in the form of Raney nickel. These catalysts can be used alone or as a mixture of two or more of the kind. Furthermore, the catalyst can also be activated by e.g. hydrogen before being used. In addition, these catalysts can also be used supported on a carrier such as activated carbon, alumina, silica, silicon carbide, diatomaceous earth, pumice, zeolite or molecular sieves.

The catalyst is used in an amount of 0.001 to 3 g of atoms, preferably 0.002 to 2 g of atoms per metal. moles of the 2-alkyl-4-amino-5-formylpyrimidine used as starting material.

The hydrogen is used in an amount of 5 to 400 moles per liter. mole of the 2-starting material used as a starting material, 15-alkyl-4-amino-5-formylpyrimidine.

The reaction is expressed at a temperature of 0 to 200 ° C, preferably room temperature to 120 ° C. Although the reaction proceeds even under atmospheric pressure, it is usually expressed under a hydrogen partial pressure of 1 to 100 kg / cm 2 (overpressure), because the reaction can proceed faster under 20 positive pressure. For the turnover, a period of approx. 0.5 to 10 hours sufficient.

According to a preferred embodiment of the present invention, the reduction reaction of the 2-alkyl-4-amino-5-formylpyrimidine is carried out in the presence of a divalent nickel (Ni ++) site in addition to the reduction catalyst mentioned above.

As the site of divalent nickel for use in the invention, mention may be made of nickel chloride, nickel bromide, nickel sulphate, nickel nitrate, nickel phosphate, nickel carbonate, nickel hydroxide, nickel acetate, nickel oxalate, nickel benzoate, nickel ammonium chloride, nickel ammonium chloride, nickel ammonium chloride, nickel ammonium chloride The divalent nickel salts can be used alone or as a combination of two or more of the kind. The divalent nickel salts can be used in the form of a hydrate (with crystal water). The amount of site to be used ranges from 0.1 to 5 moles, preferably 0.4 to 1.0 moles per mole. mole of the starting material used as 2-alkyl-4-amino-5-35 formylpyrimidine. If the amount is less than the lower limit in the above range, suppression of the formation of such by-products as 2-alkyl-4-amino-5-hydroxymethyl-pyrimidine, di- (2-alkyl) cannot be expected to the same extent. -4-amino-5-pyrimidylmethylamine and the like

DK 156723 B

3 be applied. On the contrary, if the amount is greater than the upper limit in the above range, the yield of the desired product will tend to decrease.

The invention comprises a process in which a 2-alkyl-4-5 anrino-5-formylpyrimidine is reacted simultaneously with ammonia in the form of liquid ammonia, ammonia gas or an aqueous ammonia solution and hydrogen, or in which a 2-alkyl-4- amino-5-formylpyrimidine is first reacted with ammonia and then reacted with hydrogen by introducing it into the system, in both cases in the presence of a divalent nickel site and a reduction catalyst. The reaction can also be carried out by first subjecting a 2-alkyl-4-amino-5-formylpyrimidine reaction with ammonia in the presence of a divalent nickel site and then reacting with hydrogen, which is introduced into the system after a reduction catalyst is added to it.

According to another preferred embodiment of the present invention, the preparation of a 2-alkyl-4-amino-5-formylpyrimidine is made by subjecting a 2-alkyl-4-amino-5-formylpyrimidine to a reaction of 4 to 500 mole of ammonia in 3 to 30 parts by weight of an inert solvent and, without isolating it from the reaction mixture, the obtained reaction product then added to 2 to 20 parts by weight of an inert solvent containing 4 to 300 moles of ammonia, hydrogen and the above said reduction catalyst. Examples of suitable inert solvents include all alcohols such as methanol, ethanol, propanol and butanol, ethers such as dioxane, tetrahydrofuran and diethyl ether, and hydrocarbons such as benzene, toluene, xylene, hexane and cyclohexane. Water is also a suitable inert solvent.

The first reaction with ammonia is carried out at a temperature of 0 to 130 ° C, preferably at room temperature to 110 ° C. Although the reaction proceeds under atmospheric pressure, it is usually expressed under an ammonia partial pressure of 1 to 100 kg / cm 2 (overpressure), since the reaction takes place faster under positive pressure. For the turnover, a period of approx. 0.5 to 10 hours sufficient.

It is believed that upon reaction, the 2-alkyl-4-amino-5-formylpyrimidine is converted to an aldimine of the following general formula: 35 γγπ2

Ni ^ / X \ CH = NH

DK 156723 B

4 wherein R has the meaning defined above.

Then, the reaction mixture containing a reaction product which is believed to have the above general formula is added, after removing the ammonia insoluble in inert solvent, to an inert solvent containing ammonia, hydrogen and a reduction catalyst to reduce the above-mentioned reaction. . The addition can be carried out by adding at once the reaction mixture containing the above-mentioned reaction product.

However, it is usually preferable to incorporate it gradually and continuously in 10 Idbet of approx. 0.5 to 8 hours.

The catalyst can typically be used in the same amount as previously mentioned.

Upon completion of the reaction, the 2-alkyl-4-amino-5-formylpyrimidine can be obtained in free form or in the form of a site e.g. with a mineral acid 15, after cooling the reaction mixture and subsequent removal of the insoluble matter, such as the catalyst, by isolating it by filtration in the usual manner.

The process of the invention is described in more detail below by examples. In each example, the yield of the product is based on the 2-alkyl-4-amino-5-formylpyrimidine used as the starting material.

Example 1 Into a 100 ml stainless steel autoclave was introduced 1.37 g (10 mmol) of 2-methyl-4-amino-5-formylpyrimidine, 15 ml of methanol (solvent) and 0.5 g of catalyst comprising 5% by weight of palladium supported. on active fun. The atmosphere of the system was replaced with nitrogen gas, after which 13.4 g of liquid ammonia was added.

During stirring, the temperature was raised to approx. 60 ° C, which is maintained for one hour. Hydrogen gas was then added under pressure at the same temperature, so that the pressure was approx. 40 kg / cm 2 (overpressure) and the reaction is carried out at the same temperature for 3 hours.

When the reaction was complete, the reaction mixture was cooled and the unreacted ammonia gas and hydrogen gas were shut off. Next, the autoclave was opened and the catalyst was filtered off. Then, 1N HCl was added to the filtrate and the mixture was adjusted to a pH of ca. Third

Thus, the yield of the desired product 2-methyl-4-amino-5-aminomethylpyrimidine and the by-product 2-methyl-4-amino-5-hydroxymethylpyrimidine was determined quantitatively, respectively. dihydrochloride and monohydrochloride at

DK 156723 B

5 using liquid chromatography according to standard internal method.

It was found that 2-methyl-4-amino-5-aminomethylpyrimidine and 2-methyl-4-amino-5-hydroxymethylpyrimidine had been prepared in yields of 90% and 5%, respectively.

5

Example 2

A test was carried out in the same manner as in Example 1, except that 1.51 g (10 mmol) of 2-ethyl-4-amino-5-formylpyrimidine was used as starting material instead of 2-methyl-4-amino -5-formylpyrimidine, and 10 ml of ethanol were used as solvent instead of methanol.

It was found that 2-ethyl-4-amino-5-aminomethylpyrimidine had been prepared in a 91% yield and that 2-ethyl-4-amino-5-hydroxy-methylpyrimidine had been prepared in a yield of 4.5 %.

Example 3 Into a 100 ml stainless steel autoclave are charged 1.37 g (10 mmol) of 2-methyl-4-amino-5-formylpyrimidine, 15 ml of ethanol (solvent) and 1.0 g of stabilized nickel (Trademark: "N103 ", manufactured by Nikki Kagaku Co., Ltd.; nickel: about 50% by weight and diatomaceous earth: about 50% by weight). After the atmosphere in the system was replaced by nitrogen gas, 9.0 g of liquid ammonia was added thereto. During rotation, the temperature was raised to approx. 90 ° C which was maintained for 30 minutes. Hydrogen gas was then added under pressure at the same temperature such that the pressure was about 50 kg / cm 2 (overpressure) and the reaction was carried out at the same temperature for 2 hours.

After completed turnover, further processing is carried out in the same way as in Example 1.

It was found that 2-methyl-4-amino-5-aminomethylpyrimidine and 2-methyl-4-amino-5-hydroxymethylpyrimidine had been prepared in yields of 89% and 5%, respectively.

Example 4

A test was carried out in the same manner as in Example 1, except that 1.0 g of catalyst comprising 5% by weight of platinum supported on 35 alumina was used as catalyst instead of stabilized nickel.

It was found that 2-methyl-4-amino-5-aminomethylpyrimidine and 2-methyl-4-amino-5-hydroxymethylpyrimidine had been prepared in yield.

DK 156723 B

6 ter of 87% and 6% respectively.

Example 5

A test was carried out in the same manner as in Example 3, except that 1.0 g of copper chromium powder was used as a catalyst instead of stabilized nickel and that the pressure of the hydrogen gas supplied was changed to approx. 80 kg / cm 2 (overpressure).

It was found that 2-methyl-4-amino-5-aminomethylpyrimidine had been prepared in a yield of 77% and that 2-methyl-4-amino-5-hydroxymethylpyrimidine was present as a by-product in a yield of 20% .

Example 6 Into a 100 ml stainless steel autoclave was added 1.74 g (10 mmol) of 2-methyl-4-amino-5-formylpyrimidine, hydrochloride, 25 g of 28 wt% aqueous ammonia and 1.0 g of Raney nickel (nickel content: about 40% by weight) developed and washed with water (water: about 5ml). After the atmosphere in the system had been replaced by nitrogen gas, hydrogen gas was added under pressure, so that the pressure was approx. 40 kg / cm 2 (overpressure). Thereafter, the temperature of the contents was raised with stirring and the reaction was carried out at ca. 90 ° C for 3 hours. The finishing is performed in the same way as in Example 1.

It was found that 2-methyl-4-amino-5-aminomethylpyrimidine was prepared in a 74% yield and that 2-methyl-4-amino-5-hydroxymethylpyrimidine was produced as a by-product in a yield of 14%.

25 "

Example 7 Into a 100 ml stainless steel autoclave were loaded 1.37 g (10 mmol) of 2-methyl-4-amino-5-formylpyrimidine, 30 ml of a 17% by weight methanolic solution of ammonia and a catalyst prepared by developing -30 g of 2.0 g Raney nickel (nickel content: about 40% by weight), followed by washing with water and replacing the water with methanol (methanol: about 8 ml). Then the temperature of the contents was raised during stirring and the temperature was maintained at approx. 90 ° C for 30 minutes. Thereafter, hydrogen gas was supplied under pressure at the same temperature so that the pressure 35 was approx. 40 kg / cm 2 (overpressure) and the reaction is carried out at the same temperature for 2 hours. The treatment after completion of the reaction was carried out in the same way as in Example 1.

It was found that 2-methyl-4-amino-5-aminomethylpyrimidine and

DK 156723 B

7 2-Methyl-4-amino-5-hydroxymethylpyrimidine was prepared in yields of 85% and 4%, respectively.

Example 8 5 Into a 100 ml stainless steel autoclave was added 1.37 g (10 mmol) of 2-methyl-4-amino-5-formylpyrimidine, 24 g of a 20% by weight solution of ammonia in methanol and 0.74 g (5). , 7 mmol) anhydrous nickel chloride. After the atmosphere in the system was replaced by nitrogen gas, the temperature of the contents was raised under stirring and maintained at ca. 90 ° C for one hour.

After decoupling, the autoclave was opened and 0.46 g of stabilized nickel (trade mark: "N103B" manufactured by Nikki Kagaku, Ltd.; nickel: about 50% by weight, diatomaceous earth: about 50% by weight) was added. After the atmosphere in the system was replaced by nitrogen gas, hydrogen gas was added under pressure so that the pressure was approx. 30 kg / cm 2 (overpressure). Then the temperature of the contents was raised during stirring and the reaction was carried out at approx. 90 ° C for 2 hours. After the reaction was complete, the reaction mixture was cooled and the unreacted gases etc. were withdrawn from the autoclave. The autoclave was then opened and the catalyst filtered. Then, the washing liquids obtained by washing the catalyst with methanol were combined with the filtrate and the thus-combined liquids were concentrated under reduced pressure to remove the bulk of the ammonia. Then, IN HCl was added thereto to adjust the pH to ca. 3, and the mixture was subjected to liquid chromatography to determine the reaction products quantitatively according to the internal standard method. The results are as follows: Yield of 2-methyl-4-amino-5-aminomethylpyrimidine 94.5%

Yield of 2-methyl-4-amino-5-hydroxymethylpyrimidine 0.3%

Yield of di- (2-methyl-4-amino-5-pyrimidylmethyl) amine 2.5%.

Example 9 Into a 100 ml stainless steel autoclave was introduced 1.37 g (10 mmol) of 2-methyl-4-amino-5-formylpyrimidine, 24 g of a 20% by weight solution of ammonia in methanol, 0.74 g (5). , 7 mmol) anhydrous nickel chloride and 0.46 g of stabilized nickel "N103B". After the atmosphere in the system was replaced by nitrogen gas, the contents of the contents were raised with stirring and maintained at ca. 90 ° C for 30 minutes. Hydrogen gas was then added under pressure at the same temperature so that the pressure was approx. 30 kg / cm 2 (overpressure) and the reaction is carried out at the same temperature for 2 hours followed by quantitative determination of the respective reaction products

DK 156723 B

8 following the same procedure as in Example 8. The results are as follows:

Yield of 2-methyl-4-amino-5-aminomethylpyrimidine 93.8%

Yield of 2-methyl-4-amino-5-hydroxymethylpyrimidine 0.5% Yield of di- (2-methyl-4-amino-5-pyrimidylmethyl) amine 2.5%.

Example 10

A query was made in the same way as in Example 9, except that nickel chloride used in Example 9 was not used.

Yield of 2-methyl-4-amino-5-aminomethylpyrimidine 88.3%

Yield of 2-methyl-4-amino-5-hydroxymethylpyrimidine 4.1%

Yield of di- (2-methyl-4-amino-5-pyrimidylmethyl) amine 5.8%.

Example 11 Into a 100 ml stainless steel autoclave was introduced 1.37 g (10 mmol) of 2-methyl-4-amino-5-formylpyrimidine, 24 g of a 20% by weight ammonia solution in methanol and 1.34 g (5 mmol). , 4 mmol) nickel acetate tetrahydrate. After the atmosphere in the system was replaced by nitrogen gas, the temperature of the contents was raised during stirring and maintained at ca. 90 ° C for 1 hour. After cooling off, the autoclave was opened. Then, a catalyst prepared by developing 2.0 g of Raney nickel (nickel content: about 40% by weight) and washing with water followed by a replacement of water with methanol (methanol: 6 ml) was added according to a standard procedure. , and the atmosphere in the system was replaced with nitrogen gas. Then 25 hydrogen gas was added under pressure at the same temperature so that the pressure was approx.

40 kg / cm 2 G. Then the temperature of the contents was raised under stirring and the reaction was carried out under stirring at 90 ° C for 2 hours. The results are as follows:

Yield of 2-methyl-4-amino-5-aminomethylpyrimidine 92.9% Yield of 2-methyl-4-amino-5-hydroxymethylpyrimidine 0.6%

Yield of di- (2-methyl-4-amino-5-pyrimidylmethyl) amine 2.5%.

Example 12

A test was made in the same manner as in Example 8, except that 0.75 g (5.3 mmol expressed as total nickel salts) of NiCO3 .Ni (OH) 2.4H2 O was used instead of the nickel chloride in Example 8. The results are as follows:

Yield of 2-methyl-4-amino-5-aminomethylpyrimidine 93.4%

DK 156723 B

9

Yield of 2-methyl-4-amino-5-hydroxymethylpyrimidine 0.4%

Yield of di- (2-methyl-4-amino-5-pyrimidylmethyl) amine 2.9%.

Example 13 A preliminary was made in the same manner as in Example 8 except that 1.51 g (10 mmol) of 2-ethyl-4-amino-5-formylpyrimidine was used as starting material instead of 2-methyl-4 -amino-5-formyl: pyrimidine and 30 g 20% by weight solution of ammonia in ethanol instead of 20% by weight solution of ammonia in methanol. The results are as follows: Yield of 2-ethyl-4-amino-5-aminomethylpyrimidine 95.1%

Yield of 2-ethyl-4-amino-5-hydroxymethylpyrimidine 1.5%

Yield of di- (2-ethyl-4-amino-5-pyrimidylmethyl) amine 2.0%.

Example 14 In a 100 ml stainless steel autoclave, fitted with a: high-pressure feed pump, 11 g of a 20% by weight solution of ammonia in methanol, 0.67 g of stabilized nickel (trade mark: "N103B", manufactured by Nikki Kagaku) was introduced. Cp. Ltd.; nickel about 50% by weight, diatomaceous earth: about 50% by weight) and hydrogen gas, so that the pressure was approx. 30 kg / cm 2 (overpressure). The temperature of the mixture was raised with stirring and maintained at ca. 110 ° C.

In another 100 ml stainless steel autoclave, 2 g (14.6 mmol) of 2-methyl-4-amino-5-formylpyrimidine and 24 g of a 20 wt.% Solution of ammonia in methanol were added and the mixture was subjected to reaction under stir at 90 ° C for 2 hours, followed by decoupling and opening of the autoclave. The total amount of the reaction mixture thus obtained was pressurized over 2 hours using the high pressure pressure pump to the previously prepared mixture which was stored at 110 ° C and the reaction was continued for 30 minutes at the same temperature.

After the reaction was completed, the autoclave was decoupled and the unreacted gases and the like were shut out of the autoclave. Then, the autoclave was opened and the catalyst in it was collected by filtration. Then, the washing liquids obtained by washing the catalyst with methanol were concentrated with the filtrate and the liquids thus concentrated under reduced pressure to remove ammonia. The pH of the resulting residue was adjusted to approx. 3 with 1N HCl and the respective reaction products were quantitatively determined by liquid chromatography according to a

DK 156723 B

10 internal standard method. The results are as follows:

Yield of 2-methyl-4-amino-5-aminomethylpyrimidine 94.9%

Yield of 2-methyl-4-amino-5-hydroxymethylpyrimidine 0.6%

Yield of di- (2-methyl-4-amino-5-pyrimidylmethyl) amine 0.9%.

5

Example 15

A test was made in the same way as in Example 14, except that the amount of stabilized nickel "N103B" used was changed to 1.33 g; the amount of 2-methyl-4-amino-5-formylpyrimidine 10 used was changed to 4 g (29.2 mmol), and the period of continuous feeding under pressure using the high-pressure heat pump was changed to 4 hours. The results are as follows:

Yield of 2-methyl-4-amino-5-aminomethylpyrimidine 92.9%

Yield of 2-methyl-4-amino-5-hydroxymethylpyrimidine 0.8% Yield of di- (2-methyl-4-amino-5-pyrimidylmethyl) amine 1.5%.

Example 16 In a 100 ml stainless steel autoclave, equipped with a high-pressure FPD pump, 10 g of a mixed solvent of methanol and 20 dioxane (weight ratio 6: 4), 2 g of liquid ammonia, 1.33 g of stabilized nickel "N103B are charged. "and hydrogen gas, so that the pressure was approx. 20 kg / cm 2 (overpressure). Then, the temperature of the mixture was raised while stirring and maintained at ca. 110 ° C.

In another 100 ml stainless steel autoclave, 4 g (29.2 25 mmol) of 2-methyl-4-amino-5-formylpyrimidine and 25 g of liquid ammonia were reacted in 18 g of a mixed solvent of methanol and dioxane with stirring at 60 ° C. ° C for 3 hours. After cooling, the autoclave was opened and the excess amount of ammonia removed. Then, the reaction mixture thus obtained was pressurized using the high-pressure heat pump to the previously prepared mixture, which was stored at 110 ° C for 4 hours, and the reaction was continued for 30 minutes at the same temperature.

After the turnover was completed, the further processing is carried out in the same way as in Example 14. The results are as follows:

Yield of 2-methyl-4-amino-5-aminomethylpyrimidine 90.4% Yield of 2-methyl-4-amino-5-hydroxymethylpyrimidine 1.1%

Yield of di- (2-methyl-4-amino-5-pyrimidylmethyl) amine 1.8%.

DK 156723 B

11

Example 17 Into a 100 ml stainless steel autoclave, fitted with a high pressure feed plunger, was injected with 12 g of a 20% by weight solution of ammonia in methanol, 0.67 g of stabilized nickel "N103B" and hydrogen gas, so that the pressure was approx. 30 kg / cm 2 (overpressure). Then the temperature of the mixture was raised and maintained at ca. 100 ° C while stirring.

In another 100 ml two-neck flask equipped with gas inlet rpr and with a glass filter and a reflux condenser with a silica gel rpr 4 g (29.2 mmol) of 2-methyl-4-amino-5-formylpyrimidine and 26 10 g of a 20 wt% were introduced. dissolving ammonia in methanol. Mice that introduced NH3 gas at a rate of 100 ml / min. while stirring, the reaction is carried out at 40 ° C for 10 hours followed by cooling. The entire reaction & mixture thus obtained was pressurized using the 4 hour high pressure feed pump to the previously prepared mixture stored at 100 ° C and the reaction was continued at the same temperature for 30 minutes.

After the turnover was completed, the proceeding was carried out in the same manner as in Example 14. The results are as follows:

Yield of 2-methyl-4-amino-5-aminomethylpyrimidine 90.5% Yield of 2-methyl-4-amino-5-hydroxymethylpyrimidine 1.1%

Yield of di- (2-methyl-4-amino-5-pyrimidylmethyl) amine 1.6%.

Example 18 Into a 100 ml stainless steel autoclave, equipped with a high-pressure 25 ft. Pump, was introduced a catalyst prepared by developing 2 g of a Raney nickel (nickel content: about 40% by weight) and washing with water ordinary procedure followed by replacement of water with methanol (methanol: about 12 g), 3 g of liquid ammonia and hydrogen gas, so that the pressure was approx. 30 kg / cm 2 (overpressure). Thereafter, the temperature of the mixture is maintained at stirring and maintained at ca.

90 ° C.

In another 100 ml stainless steel autoclave, 2 g (14.6 mmol) of 2-methyl-4-amino-5-formylpyrimidine and 28 g of a 20% by weight ammonia solution in methanol were introduced and the reaction was carried out at 90 ° C for 2 hours. omrpring. After cooling, the atmosphere was opened.

The entire reaction mixture thus obtained was pressurized using the high-pressure feed pump over the course of 2 hours to the previously prepared mixture stored at 90 ° C and the reaction continued.

DK 156723B

12 was set at the same temperature for 30 minutes.

After the reaction was completed, the further processing was carried out in the same manner as in Example 14. The results are as follows:

Yield of 2-methyl-4-amino-5-aminomethylpyrimidine 91.7% Yield of 2-methyl-4-amino-5-hydroxymethylpyrimidine 1.8%

Yield of di- (2-methyl-4-amino-5-pyridylmethyl) anrin 1.2%.

Claims (3)

A process for the preparation of 2-alkyl-4-amino-5-aminomethyl-pyrimidines by reductive amination of a 2-alkyl-4-amino-5-formyl-pyrimidine at a temperature of 0 to 200 ° C. the presence of a reduction catalyst selected from palladium, platinum, ruthenium, rhodium, nickel, cobalt, iron, copper and chromium in an amount of 0.001 to 3 grams atoms of metal, and b) a hydrogen amount of 5 to 400 moles, where: alkyl 4-amino-5-formylpyrimidine is simultaneously reacted with ammonia and hydrogen, or a 2-alkyl-4-amine? -5-formylpyrimidine is first reacted with ammonia and then hydrogen by evaporation thereof. and the ammonia is used in the form of liquid ammonia, ammonia gas or an aqueous ammonia solution in an amount of 4 to 500 moles, or 2) a 2-alkyl-4-amino-5-formylpyrimidine is subjected to reaction with ammonia in an amount of 4 to 500 moles in an inert solvent in an amount of 3 to 30 parts by weight and the reaction product thus obtained obtained In isolation from the reaction mixture, an inert solvent is added in an amount of 2 to 20 parts by weight, containing 4 to 20 300 moles of ammonia, hydrogen and the reduction catalyst, and optionally, under 1) as well as 2) in addition to the reduction catalyst, a divalent nickel salt is added. to the reaction system in an amount of 0.1 to 5 moles, where all moles, gram atoms and parts by weight are based on, respectively. 1 mole, 1 gram atom and 1 part by weight of 2-alkyl-4-amine-5-formylpyrimidine. 2. A process according to claim 1, characterized in that the addition of the 2-alkyl-4-amino-5-phenylpyrimidine with ammonia is expressed at a temperature of 0 to 130 ° C under an ammonia partial pressure of 1 to 100 kg / cm2 (overpressure ). 3. A process according to claim 1, characterized in that the catalytic reaction solvents are used in an amount of 2 to 20 parts by weight per minute. part by weight of 2-alkyl-4-amino-5-aminoformylpyrimidine. ! 35