KR900001197B1 - Method for preparing 2-alkyl-4-amino-5-aminomethylpyrimidine - Google Patents

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Description

Method for preparing 2-alkyl-4-amino-5-aminomethylpyrimidine

The present invention relates to a novel preparation of 2-alkyl-4-amino-5-aminomethylpyrimidine.

It is known that 2-alkyl-4-amino-5-aminomethylpyrimidine is an important intermediate of vitamin B ₁ and its homologues. (Encyclopedia do Chemical Technology, Second Edition, vol 20, 173 (1969), John Wiley & Sons, Inc.)

As a manufacturing method of 2-alkyl-4-amino-5-aminomethylpyrimidine, for example, the method of reducing 2-alkyl-4-amino-5-cyanopyrimidine (Yakugakujashi, Japan, 73, 977 ( 1953), JACS66 876 (1994); Methods of hydrolyzing 2-alkyl-4-amino-5-acetoamidomethylpyrimidine (Chem. Ber. 106 (1973), etc. are known to date.

The inventors of the present invention have conducted all kinds of studies to develop a novel preparation of 2-alkyl-4-amino-5-aminomethylpyrimidine, and as a result, 2-alkyl-4-amino-5-formylpyrimi in the presence of a reducing catalyst It was found that 2-alkyl-4-amino-5-aminomethylpyrimidine can be prepared by subjecting a dean to reductive amination reaction by a catalytic reaction between hydrogen and ammonia, thereby completing the present invention.

The starting material, i.e., the 2-alkyl-4-amino-5-formylpyrimidine used in the present invention, has the following structural formula.

Wherein R includes lower alkyl groups of 1 to 5 carbon atoms such as methyl, ethyl, propyl and butyl.

This starting material can be readily synthesized by, for example, hydrolyzing 2-alkyl-4-amino-5-dialkoxymethylpyrimidine in the presence of acid.

The starting material 2-alkyl-4-amino-5-formylpyrimidine may also be used in the form of salts with mineral acids such as sulfuric acid, nitric acid, hydrochloric acid, phosphoric acid and the like.

Examples of the reducing catalyst used in the present invention include Group VIII metals such as palladium, platinum, rhodium, ruthenium, nickel, cobalt and iron; Metals such as copper and chromium are useful. These metals are usually used in the form of metal itself. However, they can also be used in the form of salts, oxides or alloys. Furthermore, nickel may be in the form of laney nickel produced by conventional methods known in the art.

These catalysts are used alone or as a mixture of two or more thereof. Moreover, these catalysts may be activated, for example, by hydrogen before using them. Furthermore, these catalysts may be supported on a carrier such as activated carbon, alumina, silica, silicon carbide, diatomaceous earth, pumice, zeolite, and molecular sieve.

The catalyst typically uses 0.001 to 3 gram atoms, preferably 0.002 to 2 gram atoms as the metal per mole of starting material 2-alkyl-4-amino-5-formylpyrimidine.

Hydrogen is typically used at least 1 mole, preferably 5 to 400 moles per mole of the starting material 2-alkyl-4-amino-5-formyl-pyrimidine. Ammonia is used in the form of liquid ammonia, gaseous ammonia or ammonia water in an amount of at least 1 mole, preferably 4 to 500 moles, per mole of starting material 2-alkyl-4-amino-5-formylpyrimidine.

The reaction is carried out in a solvent inert to the reaction. Solvents include lower aliphatic alcohols such as methanol, ethanol propanol and butanol; Ethers such as dioxane, tetrahydrofuran and diethyl ether; Hydrocarbons such as benzene, toluene, xylene, hexane and cyclohexane; And water.

The reaction is carried out at a temperature of 0 to 200 캜, preferably at a temperature of room temperature to 120 캜. The reaction proceeds even under atmospheric pressure, but the reaction proceeds faster under a pressure higher than atmospheric pressure (static pressure), and is usually reacted under a hydrogen partial pressure of 1 to 100 kg / cm 2 G. 0.5-10 hours is enough for reaction.

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

As the salt of divalent nickel to be used in the present invention, nickel chloride, nickel bromide, nickel sulfate, nickel nitrate, nickel phosphate, nickel carbonate, nickel hydroxide, nickel acetate, nickel oxalate, nickel benzoate, nickel ammonium chloride, nickel ammonium sulfate, sulfuric acid Nickel potassium and the like. The amount of salt used is in the range of 0.1 to 5 moles, preferably 0.4 to 1.0 mole, per mole of starting material 2-alkyl-4-amino-5-formylpyrimidine.

Use of an amount below the lower limit of the above range inhibits the formation of by-products such as 2-alkyl-4-amino-5-hydroxymethylpyrimidine and di- (2-alkyl-4-amino-5-pyrimidylmethyl) amine. Can't expect the effect. On the other hand, when the amount of use exceeds the upper limit of the above range, the yield of the desired product tends to decrease.

As the reaction method, for example, a step of reacting 2-alkyl-4-amino-5-formylpyrimidine simultaneously with ammonia and hydrogen in the presence of a divalent nickel salt and a reducing catalyst, or 2-alkyl-4- The process of reacting amino-5-formylpyrimidine with hydrogen by first reacting with ammonia and then introducing hydrogen into the system can be carried out. Furthermore, 2-alkyl-4-amino-5-formylpyrimidine is first reacted with ammonia in the presence of a divalent nickel salt and then a reduction catalyst is added to the system, followed by reaction with hydrogen while introducing hydrogen into the system. You can also

According to another preferred embodiment of the present invention, 2-alkyl-4-amino-5-formylpyrimidine is reacted with ammonia in an inert solvent, and the resulting reaction product is not isolated from the reaction mixture without ammonia, hydrogen and the reduction catalyst. 2-alkyl-4-amino-5-formylpyrimidine is prepared by reducing the reaction product described above by adding to an inert solvent containing.

In the process according to a preferred embodiment, 2-alkyl-4-amino-formylpyrimidine is first reacted with ammonia in an inert solvent.

Ammonia is used in the form of liquid ammonia, gaseous ammonia or aqueous ammonia solution at least 1 mole, preferably 4 to 500 moles, per mole of the starting material 2-alkyl-4-amino-5-formylpyrimidine.

Inert solvents include those as described above.

The amount of solvent used may be used in the range of 3 to 30 parts by weight per 1 part by weight of the starting material 2-alkyl-4-amino-5-formylpyrimidine.

The reaction with the first ammonia is carried out at a temperature of 0 to 130 캜, preferably at a temperature of room temperature to 110 캜. The reaction proceeds under ambient pressure but the reaction proceeds more rapidly under constant pressure, so it is usually reacted under ammonia partial pressure of 1 to 100 kg / cm 2 G. A period of about 0.5 to 10 hours is sufficient for the reaction.

By reaction, it is thought that 2-alkyl-4-amino-5-formylpyrimidine is once converted into aldimine represented by general formula.

Where R has the same meaning as defined above.

Next, the reaction mixture containing the reaction product assumed to be represented by the above general formula (with or without removing insoluble ammonia in the inert solvent) is added to the inert solvent containing ammonia, hydrogen, and a reduction catalyst. One reaction product is reduced. The addition may be done by adding a reaction mixture containing the reaction product at a time. However, it is generally desirable to add continuously in small amounts over about 0.5 to 8 hours.

The catalyst usually uses the amounts as described above.

As ammonia, liquid ammonia, ammonia gas and aqueous ammonia solution can be used as used in the reaction step between 2-alkyl-4-amino-5-formylpyrimidine and ammonia. The amount used is at least 1 mole, preferably 4 to 300 moles per mole of the starting material 2-alkyl-4-amino-5-formylpyrimidine.

Hydrogen is usually used in the amounts described above.

The inert solvent used in this step is preferably the same as that used in the reaction step between 2-alkyl-4-amino-5-formylpyrimidine and ammonia described above. The amount used is preferably in the range of 2 to 20 parts by weight per 1 part by weight of the starting material 2-alkyl-4-amino-5-formylpyrimidine.

The reaction of this second step is carried out at a temperature of 0 to 200 캜, preferably at room temperature to 120 캜. The reaction proceeds even under ambient pressure but is usually carried out under a partial pressure of 1 to 100 kg / cm 2 G.

The reaction is sufficiently complete after approximately 0.5 to 2 hours after addition of the reaction mixture containing 2-alkyl-4-amino-5-formylpyrimidine and the reaction product obtained from ammonia.

The salts of divalent nickel described above are optionally added to the reaction system in the first and / or second stages of the reaction in order to increase the yield of the desired product.

After the reaction is completed, for example, 2-alkyl-4-amino-5 represented by the following general formula by cooling the reaction mixture, then removing the insolubles such as catalyst by filtration and isolating by conventional methods. Aminomethylpyrimidines are obtained in free form or in the form of salts with mineral acids.

In the above formula, R is defined as described above.

Next, an embodiment of the present invention will be described next. In each example, the yield of the product is based on 2-alkyl-4-amino-5-formylpyrimidine used as starting material.

Example 1

0.5 ml catalyst containing 1.37 g (10 mmol) of 2-methyl-4-amino-5-formylpyrimidine, 15 ml of methanol (solvent) and 5% by weight of palladium on 100 ml stainless steel autoclave g was introduced, the atmosphere in the system was replaced with nitrogen gas, and 13.4 g of liquid ammonia was added thereto.

The temperature was raised while stirring the contents and maintained at about 60 ° C for 1 hour. Thereafter, hydrogen was introduced into the system under pressure at the same temperature to maintain the pressure at about 40 kg / cm 2 G, and the reaction was carried out at the same temperature for 3 hours.

After completion of the reaction, the reaction mixture was cooled and the unreacted ammonia gas and hydrogen were discharged. The autoclave was then opened and the catalyst was filtered. 1N-HCl was then added to the filtrate, and the pH of the mixed solution was adjusted to about 3.

The yields of the desired product 2-methyl-4-amino-5-aminomethylpyrimidine and by-product 2-methyl-4-amino-5-hydroxymethylpyrimidine were then determined in accordance with the internal standard method by liquid chromatography, respectively. Obtained quantitatively as dihydrodolide and monohydrochloride.

As a result, it was confirmed that 2-methyl-4-amino-5-aminomethylpyrimidine and 2-methyl-4-amino-5-hydroxymethylpyrimidine were produced in yields of 90% and 5%, respectively.

Example 2

As starting material, 1.51 g (10 mmol) of 2-ethyl-4-amino-5-formylpyrimidine was used instead of 2-methyl-4-amino-5-formylpyrimidine, and 15 ml of ethanol was used as a solvent instead of methanol. The experiment was conducted in the same manner as in Example 1 except that it was used.

As a result, it was found that 2-ethyl-4-amino-5-aminomethylpyrimidine was produced in 91% yield and 2-ethyl-4-amino-hydroxymethylpyrimidine was produced in yield 4.5%.

Example 3

100 ml of stainless steel agent in autoclave, 1.37 g (10 mmol) of 2-metal-4-amino-5-formylpyrimidine, 15 ml of ethanol (solvent), and 1.0 g of Stabilized Nickel (trade name) , N103: Nickel Chemical Co., Ltd .: Nickel: about 50% by weight and diatomaceous earth: about 50% by weight). After replacing the atmosphere in the system with nitrogen air, 9.0 g of liquid ammonia was added thereto. The temperature was raised while stirring the contents and held at about 90 ° C. for 30 minutes. Then, hydrogen gas was injected at the same temperature so as to have a pressure of approximately 50 kg / cm 2 G and reacted at the same temperature for 2 hours. The reaction complete water was treated in the same manner as in Example 1.

As a result, it was confirmed that 2-methyl-4-amino-5-aminomethylpyrimidine and 2-methyl-4-amino-5-hydroxymethylpyrimidine were produced in a yield of 89% and a yield of 5%, respectively.

Example 4

The experiment was carried out in the same manner as in Example 1, except that 1.0 g of a catalyst loaded with 5% by weight of platinum instead of stabilized nickel was used as the catalyst.

As a result, it was found that 2-methyl-4-amino-5-aminomethylpyrimidine and 2-methyl-4-amino-5-hydroxymethylpyrimidine were produced in yields of 87% and 6%, respectively.

Example 5

The experiment was conducted 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 the pressure of charged hydrogen was changed to about 80 kg / cm 2 G.

As a result, 2-methyl-4-amino-5-aminomethylpyrimidine was produced in a yield of 77% and 2-methyl-4-amino-5-hydroxymethylpyrimidine was found to be a byproduct in 20% yield.

Example 6

1.74 g (10 mmol) of 2-methyl-4-amino-5-formylpyrimidine hydrochloride in 100 ml of autoclave made of stainless steel, 25 g of 28 wt% aqueous ammonia, and developed and washed with water (about 5 ml) 1.0 g of nickel (nickel content: about 40% by weight) was introduced. After replacing the atmosphere in the system with nitrogen gas, hydrogen was pressurized into the system so that the pressure was about 40 kg / cm 2 G. Subsequently, the temperature of the contents was increased while stirring, and the reaction was performed at about 90 ° C for 3 hours.

Post-treatment was carried out in the same manner as in Example 1.

As a result, it was found that 2-methyl-4-amino-5-aminomethylpyrimidine was produced in a yield of 74% and 2-methyl-4-amino-5-hydroxymethylpyrimidine was a byproduct in a yield of 14%.

Example 7

In 100 ml of stainless steel autoclave, 1.37 g (10 mmol) of 2-methyl-4-amino-5-formylpyrimidine, 30 ml of 17% by weight methanolic ammonia solution, and raney nickel (nickel content: about 40 weight) %) 2.0 g was developed, washed with water, and a catalyst prepared by replacing water with methanol (about 8 ml) was introduced.

The temperature of the contents was then raised with stirring and held at about 90 ° C. for 30 minutes. Thereafter, hydrogen was press-fitted at the same temperature so that the pressure was about 40 kg / cm 2 G, and the reaction was carried out at the same temperature for 2 hours. The treatment after completion of the reaction was carried out in the same manner as in Example 1.

As a result, it was found that 2-methyl-4-amino-5-aminomethylpyrimidine and 2-methyl-4-amino-5-hydroxymethylpyrimidine were produced in yields of 85% and 4%, respectively.

Example 8

To 100 ml of stainless steel autoclave, 1.37 g (10 mmol) of 2-methyl-4-amino-5-formylpyrimidine, 24 g of 20 wt% ammonia methanol solution, and 0.74 g (5.7 mmol) of anhydrous nickel chloride were added. After replacing the atmosphere in the system with nitrogen gas, the temperature of the contents was increased while stirring, and maintained at about 90 ° C for 1 hour. After cooling, the autoclave was opened, and 0.46 g of stabilized nickel was added (brand name, N103B, Nickki Chemical Co., Ltd .: Nickel: about 50% by weight, diatomaceous earth: about 50% by weight). After replacing the atmosphere in the system with nitrogen gas, the hydrogen gas was pressurized into the system so that the pressure was about 30 kg / cm 2 G. The temperature of the contents was then raised with stirring and reacted for 2 hours at about 90 ° C.

After completion of the reaction, the reaction mixture was cooled and then unreacted gas was discharged from the autoclave. Then the autoclave was opened and the catalyst was filtered off. The washing liquid and the filtrate obtained when washing the catalyst with methanol were combined, and the combined liquid was concentrated under reduced pressure to remove most of the ammonia.

Then, 1N-HCl was added thereto to adjust the pH to about 3, and the mixture was subjected to liquid chromatography to quantitatively obtain each reaction product by internal standard method.

The result is as follows.

Yield 94.5% of 2-methyl-4-amino-5-aminomethylpyrimidine 0.3% yield of 2-methyl-4-amino-5-hydroxymethylpyrimidine di- (2-methyl-4-amino-5- Yield 2.5% of pyrimidylmethyl) amine

Example 9

100 ml of stainless steel autoclave, 1.37 g (10 mmol) of 2-methyl-4-amino-5-formylpyrimidine, 24 g of methanol solution of 20% by weight ammonia, 0.74 g (5.7 mmol) of anhydrous nickel chloride, and stabili 0.46 g of isnickel N103B was charged. After replacing the atmosphere in the system with a nitrogen gas, the temperature of the contents was increased while stirring, and the mixture was maintained at about 90 ° C for 30 minutes.

Then, hydrogen gas was injected into the system at the same temperature so that the pressure was about 30 kg / cm 2 G, and the reaction was carried out at the same temperature, and then each reaction product was quantitatively determined in the same order as in Example 8.

2-methyl-4-amino-5- 93.8%

Yield of Aminomethylpyrimidine

2-methyl-4-amino-5- 0.5%

Yield of hydroxymethylpyrimidine

Di- (2-methyl-4-amino-5- 2.5%

Yield of pyrimidylmethyl) amine

Example 10

The experiment was conducted in the same manner as in Example 9 except that the nickel chloride used in Example 9 was not used.

2-methyl-4-amino-5- 88.3%

Yield of Aminomethylpyrimidine

2-methyl-4-amino-5- 4.1%

Yield of hydroxymethylpyrimidine

Di- (2-methyl-4-amino-5- 5.8%

Yield of pyrimidylmethyl) amine

Example 11

To 100 ml of stainless steel autoclave, 1.37 (10 mmol) of 2-methyl-4-amino-5-formylpyrimidine, 24 g of methanol solution of 20% by weight ammonia, and 1.34 g (5.4 mmol) of nickel acetate tetrahydrate were charged. did. The atmosphere of the system was replaced with nitrogen gas, and then the temperature of the contents was raised with stirring and maintained at about 90 ° C for 1 hour. After cooling the autoclave was opened. Then, a catalyst prepared by developing 2.0 g of raney nickel (nickel content: about 40% by weight), washing with water, replacing water with methanol (about 6 ml) was introduced according to a conventional method, and then replacing the atmosphere of the system with nitrogen gas. did. After that, hydrogen gas was press-fitted so that the pressure might be about 40 kg / cm <2> G. Then, the temperature of the contents was increased with stirring, and the reaction was carried out at 90 ° C. for 2 hours with stirring.

The result is as follows.

2-methyl-4-amino-5-92.9%

Yield of Aminomethylpyrimidine

2-methyl-4-amino-5- 0.6%

Yield of hydroxymethylpyrimidine

Di- (2-methyl-4-amino-5- 2.5%

Yield of pyrimidylmethyl) amine

Example 12

The experiment was conducted in the same manner as in Example 8, except that 0.75 g (5.3 mmol as total nickel salt) of NiCO ₃ · Ni (OH) ₂ · 4H ₂ O was used instead of nickel chloride in Example 8.

the results are as follow.

2-methyl-4-amino-5-93.4%

Yield of Aminomethylpyrimidine

2-methyl-4-amino-5- 0.4%

Yield of hydroxymethylpyrimidine

Di- (2-methyl-4-amino-5- 2.9%

Yield of pyrimidylmethyl) amine

Example 13

30 g of 20% by weight ammonia ethanol solution using 1.51 g (10 mmol) of 2-ethyl-4-amino-5-formylpyrimidine as starting material instead of 2-methyl-4-amino-5-formylpyrimidine Experiment was carried out in the same manner as in Example 8, except that 20% by weight of ammonia was used instead of methanol.

the results are as follow.

2-methyl-4-amino-5- 95.1%

Yield of Aminomethylpyrimidine

2-methyl-4-amino-5- 1.5%

Yield of hydroxymethylpyrimidine

Di- (2-ethyl-4-amino-5- 2.0%

Yield of pyrimidylmethyl) amine

Example 14

Into 100 ml of stainless steal autoclave equipped with a high pressure feed pump, 11 g of ammonia solution of 20% by weight of ammonia, stabilized nickel (trade name, N103B: manufactured by Nickki Chemical Co., Ltd .: nickel: about 50% by weight) Diatomaceous earth: about 50% by weight) 0.67g, and hydrogen gas to maintain the pressure at about 30kg / ㎠G. The temperature of the mixture was raised with stirring and maintained at 110 ° C.

Into another 100 ml autoclave of stainless steel, 2 g (14.6 mmol) of 2-methyl-4-amino-5-formylpyrimidine and 24 g of 20% by weight ammonia were introduced and then the mixture was stirred at 90 ° C. for 2 hours. Reaction was followed by cooling and then opening the autoclave. Using the high pressure feed pump, the total amount of the reaction mixture obtained was press-fitted into the previously prepared mixture maintained at 110 ° C. over 2 hours, and the reaction was continued for 30 minutes at the same temperature.

After completion of the reaction, the autoclave was cooled and unreacted gas was discharged from the autoclave. Then, it was discharged from the autoclave. Then, the autoclave was opened and the catalyst therein was collected by filtration.

The washings obtained by washing the catalyst with methanol were then combined with the filtrate and the combined liquids were concentrated under reduced pressure to remove ammonia. The pH value of the obtained residue was adjusted to about 3 with 1N-HCl, and each reaction product was quantitatively determined by liquid chromatography according to the standard method.

the results are as follow.

2-methyl-4-amino-5-94.8%

Yield of Aminomethylpyrimidine

2-methyl-4-amino-5- 0.6%

Yield of hydroxymethylpyrimidine

Di- (2-methyl-4-amino-5- 0.9%

Yield of pyrimidylmethyl) amine

Example 15

Change the usage of stabilized nickel N103B to 1.33 g, and change the usage of 2-methyl-4-amino-5-formylpyrimidine to 4 g (29.2 mmol): Continuously under pressure using a high pressure feed pump The experiment was conducted in the same manner as in Example 14 except that the feeding time was changed to 4 hours.

the results are as follow.

2-methyl-4-amino-5-92.9%

Yield of Aminomethylpyrimidine

2-methyl-4-amino-5- 0.8%

Yield of hydroxymethylpyrimidine

Di- (2-methyl-4-amino-5- 1.5%

Yield of pyrimidylmethyl) amine

Example 16

In a stainless steel 100 ml autoclave equipped with a high pressure feed pump, 10 g of a mixed solvent of methanol and dioxane (weight ratio 6: 4), 2 g of liquid ammonia, 1.33 g of stabilized nickel N103B, and a pressure of 20 kg / cm 2 G were maintained. Introduced hydrogen gas. Then, the temperature of the mixture was raised while stirring to maintain at 110 ° C.

Meanwhile, in another 100 ml autoclave made of stainless steel, 4 g (29.2 mmol) of 2-methyl-4-amino-5-formylpyrimidine and 25 g of liquid ammonia were stirred in 18 g of a mixed solvent of methanol and dioxane. The reaction was carried out at 60 ° C. for 3 hours. After cooling, the autoclave was opened to remove excess ammonia.

Then, the entire amount of the reaction mixture obtained was introduced under pressure over 4 hours into a previously prepared mixture maintained at a temperature of 110 ° C. using a high pressure feed pump, and the reaction was continued for 30 minutes at the same temperature.

After the reaction was completed, the same procedure as in Example 14 was performed.

the results are as follow.

2-methyl-4-amino-5- 90.4%

Yield of Aminomethylpyrimidine

2-methyl-4-amino-5- 1.1%

Yield of hydroxymethylpyrimidine

Di- (2-methyl-4-amino-5- 1.8%

Yield of pyrimidylmethyl) amine

Example 17

Into a 100 ml autoclave made of stainless steel equipped with a high-pressure feed pump, a hydrogen gas for introducing 12 g of a 20 wt% methanol solution of ammonia, 0.67% of stabilized nickel N103B and a pressure of 30 kg / cm 2 G was introduced. The temperature of the mixture was then raised and kept at 100 ° C. with stirring.

Meanwhile, 4 g (29.2 mmol) of 2-methyl-4-amino-5-formylpyrimidine and 20% by weight of ammonia in a 100 ml two-necked flask equipped with a gas introduction tube with a glass filter and a reflux capacitor with a silica gel tube 26 g were introduced.

The reaction was cooled for 10 hours at 40 ° C. while introducing NH ₃ gas with stirring at a rate of 100 m / min. The total amount of the reaction mixture thus obtained was injected into the previously prepared mixture maintained at 100 ° C. over 4 hours using a high pressure feed pump, and the reaction was continued for 30 minutes at the same temperature. After the reaction was completed, the same treatment as in Example 14 was performed.

the results are as follow.

2-methyl-4-amino-5-90.5%

Yield of Aminomethylpyrimidine

2-methyl-4-amino-5- 1.1%

Yield of hydroxymethylpyrimidine

Di- (2-methyl-4-amino-5- 1.6%

Yield of pyrimidylmethyl) amine

Example 18

A catalyst prepared by developing 2 g of raney nickel (nickel content: about 40% by weight) in a stainless steel 100 ml autoclave equipped with a high pressure feed pump, washing with water by a conventional method, and then replacing the water with methanol (about 12 g). Then, 3 g of liquid ammonia and hydrogen gas for introducing a pressure of 30 kg / cm 2 G were introduced. Then, the temperature of the mixture was raised while stirring to maintain at 90 ° C.

Meanwhile, 2 g (14.6 mmol) of 2-methyl-4-amino-5-formylpyrimidine and 28 g of methanol solution of 20 wt% ammonia were introduced into another 100 ml autoclave made of stainless steel, and stirred at 90 ° C. for 2 hours. Reaction was carried out. After cooling the autoclave was opened. Then, the entire amount of the reaction mixture obtained in the previously prepared mixture kept at 90 ° C. was indented over 2 hours using a high pressure feed pump, and the reaction was continued for 30 minutes at the same temperature. After the reaction was completed, the same treatment as in Example 14 was performed.

the results are as follow.

2-methyl-4-amino-5- 91.7%

Yield of Aminomethylpyrimidine

2-methyl-4-amino-5- 1.8%

Yield of hydroxymethylpyrimidine

Di- (2-methyl-4-amino-5- 1.2%

Yield of pyrimidylmethyl) amine

Claims (14)

A process for preparing 2-alkyl-4-amino-5-aminomethylpyrimidine characterized by catalyzing 2-alkyl-4-amino-5-formylpyrimidine with hydrogen and ammonia in the presence of a reducing catalyst. The method according to claim 1, wherein a salt of divalent nickel is added to the reaction system in addition to a reduction catalyst. The process according to claim 2, wherein a salt of divalent nickel is used at 0.1 to 5 moles per mole of 2-alkyl-4-amino-5-formylpyrimidine. The process of claim 1 or 2, wherein the reaction product is reacted with ammonia in an inert solvent and the reaction product is reduced from the reaction mixture to reduce the reaction product thus obtained. A process for producing a non-isolated, inert solvent containing ammonia, hydrogen and a reducing catalyst. The process according to claim 1 or 2, wherein 5 to 400 moles of hydrogen are used per mole of 2-alkyl-4-amino-5-formylpyrimidine. The catalyst according to claim 1 or 2, wherein the reduction catalyst contains a metal atom selected from the group consisting of palladium, rhodium, platinum, ruthenium, nickel, cobalt, iron, copper and chromium, and 2-alkyl-4-amino- A method according to claim 1, wherein the metal is used per mole of 5-formylpyrimidine in an amount of 0.001 to 3 gram atoms. The process according to claim 1 or 2, wherein the reaction is carried out at a temperature of 0 to 200 캜. 3. Ammonia according to claim 1 or 2, characterized in that ammonia is used in the form of liquid ammonia, ammonia gas and ammonia water in an amount of 4 to 500 moles per mole of 2-alkyl-4-amino-5-formylpyrimidine. Manufacturing method. The amount of 4 to 500 moles per mole of 2-alkyl-4-amino-5-formylpyrimidine according to claim 4, wherein the ammonia for reaction with 2-alkyl-4-amino-5-formylpyrimidine is added. To a liquid ammonia, ammonia gas or ammonia water. The solvent for reaction of 2-alkyl-4-amino-5-formylpyrimidine with ammonia is 3 to 30 per 1 part by weight of 2-alkyl-4-amino-5-formylpyrimidine. A production method characterized by the use of the amount by weight. The production process according to claim 4, wherein the reaction between 2-alkyl-4-amino-5-formylpyrimidine and ammonia is performed at an ammonia partial pressure of 1 to 100 kg / cm 2 G at a temperature of 0 to 130 ° C. The production process according to claim 1 or 2, wherein the catalytic reaction is carried out at a temperature of 0 to 200 캜. Ammonia for catalysis is used in the form of liquid ammonia, ammonia gas and ammonia water in an amount of 4 to 300 moles per mole of 2-alkyl-4-amino-5-formylpyrimidine. The manufacturing method to make. The process according to claim 4, wherein the catalyst for catalysis is used in an amount of 2 to 20 parts by weight per 1 part by weight of 2-alkyl-4-amino-5-formylpyrimidine.