JPS626711B2 - - Google Patents

Description

[Detailed Description of the Invention] The present invention is based on the structural formula The present invention relates to a novel 4,5-diamino-2-hydroxypyrimidine-6-carbonitrile represented by and a method for producing the same.

The 4,5-diamino-2-hydroxypyrimidine-6-carbonitrile of the present invention is a compound having the physical properties shown below.

Infrared absorption spectrum (KBr-disc): 3475,
3400, 3300, 3175, 2220, 1720, 1640~1660,
1460,775cm ^-1 .

^1H -nuclear magnetic resonance spectrum (d6-DMSO):
δ5.80 (s, 2H), 7.30 (b, 2H), 9.43 (s,
1H).

¹³ C—Nuclear magnetic resonance spectrum d6—DMSO+Cr
(AcAc) ₃ ; 166.190(4), 163.701(2), 118.921
(CN), 115.761(5), 99.371(6)ppm. Mass spectrum m/e = 151 (M ⁺ , 95%), 134 (M ⁺ −OH, 31
%), 81 (134—(CN) ₂ H, 55%), 54
((HCN) ₂ , 83%).

The 4,5-diamino-2-hydroxypyrimidine-6-carbonitrile of the present invention is an important compound that can serve as an intermediate for the synthesis of useful substances. That is, 4,5-diamino-2-hydroxypyrimidine-
6-Carbonitrile is converted into an amide that is easily converted to an alkali, and then treated under Hoffmann reaction conditions to form a bacteriophage inhibitor
29428) and other useful effects. Regarding the production of isoguanine, a method via 4-dianoimidazole-5-carboxamide has been known (Japanese Patent Application Laid-open No. 1973-
54587)) is not satisfactory as an industrial production method in terms of yield and number of steps. Furthermore, to describe the usefulness of the present invention, 4,5-diamino-2
-Hydroxypyrimidine-6-carbonitrile can be prepared by adding amino groups at the 4- and 5-positions by various known methods.
For example, using orthoformic acid ester, 6-cyano-2-hydroxypurine can be derived, which can also be derived into various purine carboxylic acid derivatives and aminomethylpurines, as well as xanthine with sulfuric acid and caffein, theobromine, etc. can lead to useful substances.

The present inventors used diaminomaleonitrile (DAMN), a hydrocyanic acid tetramer that has been produced industrially at relatively low cost in recent years, and nitrourea, which is also easily available industrially, as raw materials, and developed , 5-diamino-2-hydroxypyrimidine-6-carbonitrile and found that it is useful as an industrial raw material, leading to the completion of the present invention.

Based on the research conducted by the inventors, it is estimated that the present invention proceeds through the following mechanism. It can be said that this is a new type of pyrimidine synthesis reaction that has never been seen before.

The production method of the present invention involves reacting diaminomaleonitrile and nitrourea in the presence of a base catalyst to produce 4,5-diamino-2 represented by the structural formula ().
-Hydroxypyrimidine-6-carbonitrile is produced.

The present invention requires that the reaction be carried out in the presence of a base catalyst. As base catalysts, methylamine, ethylamine, propylamine, dimethylamine,
Amines such as diethylamine, dipropylamine, trimethylamine, triethylamine, tripropylamine, allylamine, diallylamine, triallylamine, cyclohexylamine, aniline, methylaniline, benzylamine, diphenylamine, triphenylamine, piperidine, piperazine, pyridine, naphthylamine, sodium A wide range of examples include alkoxides such as methoxide, sodium ethoxide and potassium t-butoxide, and alkali metal hydroxides such as sodium hydroxide and potassium hydroxide. In particular, it is preferable to use amines because the reaction proceeds smoothly. The amount of the base catalyst used is usually from the so-called catalytic amount to about 1/5 mole based on the reactants. In this method, if a base catalyst is not present, the reaction does not proceed at all, and only the raw material is recovered (see Comparative Example below). In carrying out the reaction, it is preferable to use a solvent, and organic polar solvents such as acetonitrile and alcohol can be used. Among these organic polar solvents, acetonitrile can be said to be a preferable solvent in terms of yield and purity. The reaction proceeds easily at 30 to 100°C and is usually completed in 30 minutes to 3 hours, although it varies depending on the type and amount of the base catalyst.

After the reaction, 4,5-diamino-2-hydroxypyrimidine-6-carbonitrile having a purity sufficient for practical use can be isolated by simply filtering the precipitated product.

Hereinafter, the present invention will be explained in more detail with reference to Examples and Comparative Examples.

Example 1 A 100 ml Erlenmeyer flask was charged with 4.3 g of diamino maleonitrile and 40 ml of acetonitrile and heated to 60°C. When a solution was obtained, 5.3 g of nitrourea was added, and then 0.5 ml of triethylamine was added dropwise. As the triethylamine was added dropwise, the nitrourea began to dissolve, and at the same time, bubbles started to form (N ₂ O) and an ocher-colored product began to precipitate. After the triethylamine dropwise addition was completed, the mixture was stirred for 30 minutes, then returned to room temperature, and stirred for 30 minutes. After cooling, the crystals were filtered out and washed with acetonitrile, and the 4,5-diamino-2 gradually changed color (sinter) from around 220°C. -Oxy-6-
3.8 g (63%) of pyrimidine carbonitrile was obtained. This was recrystallized from water.

Calculated value for C ₅ H ₅ N ₅ O: C, 39.73; H, 3.33; N, 46.34 Actual value: C, 39.27; H, 3.34; N, 45.26 Example 2 Diaminomaleonitrile, acetonitrile, nitro in Example 1 Example 1: The amount of urea was made the same, and the amount of triethylamine was made half.
Perform the same operation as 4,5-diamino-2-
Hydroxy-6-pyrimidine carbonitrile 3.5
g (58%).

Example 3 Diaminomaleonitrile 2.2g, nitrourea 2.3
A mixed suspension of 10 ml of ethanol, 10 ml of triethylamine, and 0.5 ml of triethylamine was heated to 50 to 60°C. After about 10 minutes, foaming started and a precipitate was deposited. 30 min at 60℃, 1 at room temperature
After stirring for an hour, it was filtered, washed with ethanol,
Crude product 4,5-diamino-2-hydroxy-6
-1.3g (43%) of pyrimidine carbonitrile was obtained. Although the product obtained here was more strongly colored than the product obtained in acetonitrile (Example 1 or 2), the infrared spectra were almost the same.

Example 4 Place 1.1 g of diaminomaleonitrile and 10ml of acetonitrile on an 80°C oil bath, and add 1.6 g of nitrourea and 2N-
Add 0.3ml of sodium hydroxide aqueous solution and leave it as it is 3
The mixture was stirred while heating for hours. Thereafter, it was cooled, filtered, and washed with acetonitrile to obtain 1.0 g (66%) of 4,5-diamino-2-hydroxy-6-pyrimidinecarbonitrile.

Example 5 1.1 g of diaminomaleonitrile and 10 ml of acetonitrile were placed on an 80° C. oil bath, and to the dissolved diaminomaleonitrile were added 1.6 g of nitrourea and 0.3 ml of piperidine, followed by stirring while heating for 2 hours. It was then cooled, filtered off and washed with acetonitrile. Quantification by infrared spectroscopy revealed that 0.22 g (16%) of 4,5-diamino-2-hydroxy-6-pyrimidinecarbonitrile was produced.

Comparative example 1 Diaminomaleonitrile 1.1g, nitrourea 1.2
g, a mixed suspension of 10 ml of acetonitrile at 50-60℃
The mixture was stirred for 1 hour. Although the raw materials were almost dissolved by heating, no bubbles were observed. Thereafter, the temperature was returned to room temperature, the mixture was stirred for 1 hour, and the crystals were filtered off. This was confirmed to be a raw material by thin layer chromatography and infrared absorption spectroscopy (thin layer chromatography developing solvent: ethyl acetate Rf value DAMN = 0.67 nitrourea = 0.38).

Comparative Example 2 In Comparative Example 1 above, the solvent acetonitrile 10ml
was replaced with 10 ml of ethanol and stirred while heating at 80 to 90°C for 3 hours. It was confirmed by thin layer chromatography that this was unreacted.

Claims (1)

[Claims] 1 4,5-diamino-2-hydroxypyrimidine-6-carbonitrile. 2. 4,5-diamino-2-hydroxypyrimidine, which is characterized by reacting diaminomaleonitrile and nitrourea in the presence of a base catalyst.
6-Method for producing carbonitrile. 3 Claim 2 in which the base catalyst is an amine
The method described in section.