Alkyl uracil derivative as well as preparation method and application thereof

Abstract

The invention provides an alkyl uracil derivative and a preparation method and application thereof, and relates to the technical field of organic synthesis.The preparation method comprises the following steps that a uracil analogue and olefin are subjected to a hydrogenation alkylation reaction under the action of an iron catalyst and a hydrogen source, and the alkyl uracil derivative is obtained; the iron catalyst comprises at least one of iron nitrate nonahydrate, ferrous nitrate, ferric chloride, ferrous chloride, ferric sulfate and ferric oxalate; the hydrogen source comprises at least one of sodium borohydride, lithium borohydride, lithium aluminum hydride, triphenyl silicon, triethyl silicon and borane. According to the present invention, the olefin is adopted as the alkyl raw material, the pre-functionalization is not required, the specific catalyst and the specific hydrogen source are combined, the hydrogenation alkylation reaction of the olefin and the uracil analogue is successfully achieved, and the technical effect of constructing a series of alkyl uracil derivatives is achieved. According to the invention, the reaction can be carried out at room temperature without light and heat conditions, the reaction time is short, and the functional group tolerance is better.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis, and in particular to an alkyluracil derivative, its preparation method, and its application. Background Technology

[0002] Olefins (such as ethylene, propylene, and butadiene) are core products of the petrochemical industry, with a global annual production exceeding 100 million tons. They are the basic monomers for polymer materials such as plastics, rubber, and fibers, and also important active molecular skeletons. Carbon-carbon double bonds are widely present in natural products (such as terpenes and steroids) and drug molecules; for example, artemisinin (an antimalarial drug) and paclitaxel (an anticancer drug) both contain olefin structures. Olefins are also the "Transformers" of organic synthesis, transforming simple double bonds into countless functional molecules, ranging from plastics to drugs, from fuels to liquid crystals, through diverse reaction types. The reactivity and modifiability of olefins make them an indispensable tool for chemists in constructing complex molecules.

[0003] Nitrogen-containing heterocycles are core groups in many natural and synthetic compounds and are widely found in pharmaceutical and functional material systems. Uracil, as an important class of nitrogen-containing aromatic heterocyclic compounds, has attracted widespread attention due to its significant biological activity across multiple pharmacological dimensions. Existing studies have shown that many important bioactive molecules and clinical drugs contain uracil structures, such as diclazuril, c-Met kinase inhibitors, 5-HT1A receptor modulators, 6-azauridine (antiviral agents), herpes simplex virus inhibitors, antibacterial agents, HIV-1 reverse transcriptase inhibitors, interleukin-5 inhibitors, and TAM kinase inhibitors.

[0004] Given the wide range of applications and significant value of uracil, effective structural modification is crucial for expanding its applications and enhancing its drug activity. Modifying uracil with olefins can improve its drug activity, making it possible for this product to be used in the pharmaceutical field.

[0005] In recent years, the alkylation reaction of uracil has developed rapidly. Most alkyl precursors have complex structures, while hydrogen alkylation reactions are less common.

[0006] In view of this, the present invention is hereby proposed. Summary of the Invention

[0007] One of the objectives of this invention is to provide a method for preparing alkyluracil derivatives. By using olefins as alkyl raw materials, without the need for prefunctionalization, and by employing specific catalysts and hydrogen sources, the reaction conditions are mild and the reaction time is short. This method successfully achieves the hydrogenation and alkylation reaction of olefins with uracil analogs, thus achieving the technical effect of constructing a series of alkyluracil derivatives.

[0008] The second objective of this invention is to provide an alkyluracil derivative.

[0009] The third objective of this invention is to provide an application of alkyluracil derivatives that is beneficial for improving drug preparation efficiency.

[0010] In order to achieve the above-mentioned objectives of the present invention, the following technical solution is adopted: In a first aspect, a method for preparing an alkyluracil derivative includes the following steps: The uracil analogue was subjected to a hydrogenation-alkylation reaction with an olefin under the action of an iron catalyst and a hydrogen source to obtain the alkyluracil derivative. The iron catalyst includes at least one of ferric nitrate nonahydrate, ferrous nitrate, ferric chloride, ferrous chloride, ferric sulfate, and ferric oxalate. The hydrogen source includes at least one of sodium borohydride, lithium borohydride, lithium aluminum hydride, triphenylsilane, triethylsilane, and borane.

[0011] Furthermore, the uracil analogue is a pharmacologically active uracil group and has the following structure: ; R1 is selected from hydrogen, benzyl, naphthalenebenzyl, alkyl, alkenyl-substituted alkyl, alkynyl-substituted alkyl, or ester-substituted alkyl; R2 is selected from hydrogen, benzyl, naphthalenebenzyl, alkyl, alkenyl-substituted alkyl, alkynyl-substituted alkyl, or ester-substituted alkyl.

[0012] Furthermore, the olefin includes at least one of cyclic olefins and chain olefins; Preferably, the cyclic olefin includes at least one selected from cyclohexene, cyclopentene, and cyclooctene; Preferably, the chain olefin includes at least one selected from hexene, halogen-substituted olefins, alcohol-substituted olefins, ester-substituted olefins, ether-substituted olefins, and phenyl-substituted olefins.

[0013] Furthermore, the iron catalyst is ferric nitrate nonahydrate; Preferably, the hydrogen source is sodium borohydride; Preferably, the solvent used in the hydrogenation alkylation reaction includes at least one of ethanol, acetonitrile, dichloromethane, dimethyl sulfoxide, N,N-dimethylformamide, and N,N-dimethylacetamide; Preferably, the solvent is a mixture of ethanol and acetonitrile; Preferably, the volume ratio of ethanol to acetonitrile is 1:1.

[0014] Furthermore, the molar ratio of the uracil analog to the olefin is 1:1 to 9; Preferably, the molar ratio of the uracil analog to the olefin is 1:3.

[0015] Furthermore, the molar ratio of the uracil analog to the iron catalyst is 1:1 to 9; Preferably, the molar ratio of the uracil analog to the iron catalyst is 1:4.

[0016] Furthermore, the molar ratio of the uracil analog to the hydrogen source is 1:1 to 9; Preferably, the molar ratio of the uracil analog to the hydrogen source is 1:4.

[0017] Furthermore, the hydrogenation alkylation reaction is carried out at a temperature of 20°C to 30°C for a time of 0.1 h to 3 h.

[0018] Secondly, an alkyluracil derivative is prepared by any of the preparation methods described above; The alkyluracil derivative has the following structure: .

[0019] Thirdly, the application of the aforementioned alkyluracil derivative in drug preparation.

[0020] Compared with the prior art, the present invention has at least the following beneficial effects: The method for preparing alkyluracil derivatives provided by this invention, on the one hand, uses olefins as alkyl raw materials without the need for pre-functionalization; on the other hand, it uses an iron catalyst for the first time in the alkylation reaction of uracil, realizing the hydrogen alkylation reaction of olefins and uracil analogs. In summary, this invention utilizes olefins as alkyl raw materials, combined with specific catalysts and specific hydrogen sources, without the need for light and heat, and can react at room temperature. The reaction time is short, and it has good functional group tolerance, successfully realizing the hydrogen alkylation reaction of olefins and uracil analogs, achieving the technical effect of constructing a series of alkyluracil derivatives.

[0021] The application of the alkyluracil derivatives provided by this invention is beneficial to improving the drug preparation effect. Attached Figure Description To more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0022] Figure 1This is a schematic diagram illustrating the synthesis of alkyluracil derivatives from uracil analogs and olefins according to one embodiment of the present invention. Figure 2 The proton spectrum of the target product provided in Example 1 of this invention; Figure 3 The carbon spectrum of the target product provided in Example 1 of the present invention; Figure 4 The proton spectrum of the target product provided in Example 2 of this invention; Figure 5 The carbon spectrum of the target product provided in Example 2 of the present invention; Figure 6 The proton spectrum of the target product provided in Example 3 of this invention; Figure 7 The carbon spectrum of the target product provided in Example 3 of the present invention; Figure 8 The proton spectrum of the target product provided in Example 4 of this invention; Figure 9 The carbon spectrum of the target product provided in Example 4 of the present invention. Detailed Implementation

[0023] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0024] According to a first aspect of the present invention, a method for preparing an alkyluracil derivative is provided, comprising the following steps: Uracil analogs were hydrogenated and alkylated with olefins under the action of an iron catalyst and a hydrogen source to obtain alkyluracil derivatives. The iron catalyst includes at least one of ferric nitrate nonahydrate, ferrous nitrate, ferric chloride, ferrous chloride, ferric sulfate, and ferric oxalate; The hydrogen source includes at least one of sodium borohydride, lithium borohydride, lithium aluminum hydride, triphenylsilane, triethylsilane, and borane.

[0025] This invention utilizes olefins as alkyl raw materials, combined with specific catalysts and specific hydrogen sources, to achieve the reaction at room temperature without the need for light and heat. The reaction time is short, and it has good functional group tolerance. It successfully realizes the hydrogenation and alkylation reaction of olefins with uracil analogs, achieving the technical effect of constructing a series of alkyluracil derivatives.

[0026] In a preferred embodiment, the uracil analog may be a pharmacologically active uracil group and may have the following structure: ; R1 is selected from hydrogen, benzyl, naphthalenebenzyl, alkyl, alkenyl-substituted alkyl, alkynyl-substituted alkyl, or ester-substituted alkyl; R2 is selected from hydrogen, benzyl, naphthalenebenzyl, alkyl, alkenyl-substituted alkyl, alkynyl-substituted alkyl, or ester-substituted alkyl.

[0027] In a preferred embodiment, the olefin includes, but is not limited to, at least one of cyclic olefins and chain olefins.

[0028] In a preferred embodiment, the cyclic olefins include, but are not limited to, at least one of cyclohexene, cyclopentene, and cyclooctene.

[0029] In a preferred embodiment, the chain olefin includes, but is not limited to, at least one of hexene, halogen-substituted olefins, alcohol-substituted olefins, ester-substituted olefins, ether-substituted olefins, and phenyl-substituted olefins.

[0030] A typical preparation method for an alkyluracil derivative is described in [reference needed]. Figure 1 This includes the following steps: Using uracil containing the drug-active group and olefins as starting materials, a solvent, an iron catalyst, and a hydrogen source were added. A free radical reduction coupling reaction, i.e., a hydrogenation-alkylation reaction, occurred at room temperature. The reaction was monitored by TCL. After the reaction was completed, the mixture was extracted, and the combined organic phases were subjected to vacuum distillation. The resulting alkyluracil derivatives were then separated by column chromatography.

[0031] In a preferred embodiment, the iron catalyst can be ferric nitrate nonahydrate, and the hydrogen source can be sodium borohydride, which is more conducive to improving the synthesis effect of the target product.

[0032] In a preferred embodiment, the solvent used in the reaction includes, but is not limited to, at least one of ethanol, acetonitrile, dichloromethane, dimethyl sulfoxide, N,N-dimethylformamide, and N,N-dimethylacetamide.

[0033] In a preferred embodiment, the solvent can be a mixture of ethanol and acetonitrile, with a volume ratio of ethanol to acetonitrile of 1:1, which is more conducive to improving the synthesis effect of the target product.

[0034] Iron catalyst and sodium borohydride form an iron-hydrogen species (FeH) in a mixed solvent. The Fe(III) salt undergoes single-electron oxidation to generate a hydrogen radical. The hydrogen radical further adds to cyclohexene to form an alkyl radical. The alkyl radical adds to the C6 position of uracil to obtain a nitrogen-centered radical intermediate. The benzyl CH bond is deprotonated to generate a radical anion intermediate, which is then oxidized by Fe(III) to generate the target product.

[0035] In a preferred embodiment, the molar ratio of uracil analog to olefin can be 1:1 to 9, and typical but non-limiting molar ratios are, for example, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, and 1:9, and can be further preferred to be 1:3.

[0036] In a preferred embodiment, the molar ratio of uracil analog to iron catalyst can be 1:1 to 9, and typical but non-limiting molar ratios are, for example, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, and 1:9, and can be further preferred to be 1:4.

[0037] In a preferred embodiment, the molar ratio of uracil analog to hydrogen source can be 1:1 to 9, and typical but non-limiting molar ratios are, for example, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, and 1:9, and can be further preferred to be 1:4.

[0038] In a preferred embodiment, the reaction is carried out at room temperature, and the reaction temperature can be 20°C to 30°C, for example, 20°C, 22°C, 24°C, 26°C, 28°C, or 30°C, but is not limited thereto. The reaction time can be 0.1h to 3h, for example, 0.1h, 0.5h, 1h, 2h, or 3h, but is not limited thereto, and is more preferably 0.5h.

[0039] In summary, this invention enables the efficient synthesis of alkyluracil derivatives by conducting the reaction at room temperature, cleverly utilizing the metal catalytic reaction mechanism to effectively avoid light pollution; more importantly, the reaction is successfully completed at room temperature, exhibiting not only rapid reaction but also good functional group tolerance.

[0040] According to a second aspect of the present invention, an alkyluracil derivative is provided, which is prepared by any of the preparation methods described above; This alkyluracil derivative has the following structure: .

[0041] According to a third aspect of the present invention, the use of the above-described alkyluracil derivative in pharmaceutical preparation is provided.

[0042] The application of alkyluracil derivatives in this invention is beneficial to improving drug preparation efficiency.

[0043] The present invention will be further illustrated below by way of examples. Unless otherwise specified, the materials in the examples are prepared according to existing methods or purchased directly from the market.

[0044] Example 1 A method for preparing an alkyluracil derivative includes the following steps: 2,4 Dinaphthylbenzylazuracil (0.2 mmol), cyclohexene (0.6 mmol), sodium borohydride (0.9 mmol), ferric nitrate nonahydrate (0.9 mmol), and solvent (a mixture of ethanol and acetonitrile) were added to the reactor and stirred at room temperature for 0.5 h. The reaction was monitored by TCL. After the reaction was completed, the mixture was extracted with ethyl acetate and saturated brine. The combined organic phases were subjected to vacuum distillation and separated by column chromatography (using a mixture of petroleum ether and ethyl acetate as the eluent, with a volume ratio of petroleum ether to ethyl acetate of 15:1) to obtain the target product 6-cyclohexyl-2,4-bis(naphthyl-2-ylmethyl)-1,2,4-triazine-3,5(2H,4H)-dione, with a yield of 70%.

[0045] The structure of the target product is as follows: .

[0046] The proton NMR spectrum of the target product is shown below. Figure 2 Carbon spectrum Figure 3 The structural characterization data are as follows: 1 H NMR (600 MHz, Chloroform-d) δ 7.94 (s, 1H), 7.85 (s, 1H), 7.83 –7.76 (m, 6H), 7.60 (dd, J = 8.4, 1.5 Hz, 1H), 7.52 (dd, J = 8.4, 1.4 Hz, 1H), 7.49 – 7.43 (m, 4H), 5.24 (s, 2H), 5.23 (s, 2H), 2.93–2.84 (m, 1H), 1.92 –1.85 (m, 2H), 1.84 – 1.76 (m, 2H), 1.72 (d, J = 12.8 Hz, 1H), 1.43–1.32 (m,4H), 1.26 – 1.21 (m, 1H); 13 C NMR (151 MHz, CDCl3) δ155.8, 149.2, 149.1, 133.4, 133.4, 133.3, 133.1, 133.1, 128.8, 128.6, 128.4, 128.2, 128.1, 128.0, 127.8, 127.7, 127.3, 126.4, 126.4, 126.3, 126.2, 55.5, 44.5, 38.6, 30.6, 26.2, 26.1.

[0047] Example 2 A method for preparing an alkyluracil derivative includes the following steps: 2,4-Dibenzyluracil (0.2 mmol), cyclopentene (0.6 mmol), sodium borohydride (0.9 mmol), ferric nitrate nonahydrate (0.9 mmol), and solvent (a mixture of ethanol and acetonitrile) were added to a reactor and stirred at room temperature for 0.5 h. The reaction was monitored by TCL. After the reaction was completed, the mixture was extracted with ethyl acetate and saturated brine. The combined organic phases were subjected to vacuum distillation and separated by column chromatography to obtain the target product 2,4-dibenzyl-6-cyclopentyl-1,2,4-triazine-3,5(2H,4H)-dione, with a yield of 80%.

[0048] The structure of the target product is as follows: .

[0049] The proton NMR spectrum of the target product is shown below. Figure 4 Carbon spectrum Figure 5 The structural characterization data are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 7.42 – 7.37 (m, 2H), 7.32 – 7.29 (m,2H), 7.25 – 7.16 (m, 6H), 4.98 (s, 2H), 4.97 (s, 2H), 3.28 – 3.11 (m, 1H),1.92 – 1.79 (m, 2H), 1.65 – 1.59 (m, 4H), 1.56 – 1.51 (m, 2H); 13 C NMR (151 MHz, CDCl3) δ156.1, 149.0, 148.4, 136.0, 135.9, 129.5, 128.9, 128.7, 128.6, 128.4, 128.2, 128.0, 55.3, 44.2, 40.2, 30.5, 25.4.

[0050] Example 3 A method for preparing an alkyluracil derivative includes the following steps: 2,4-Di(4-methylbenzyl)uracil (0.2 mmol), cyclooctene (0.6 mmol), sodium borohydride (0.9 mmol), ferric nitrate nonahydrate (0.9 mmol), and solvent (a mixture of ethanol and acetonitrile) were added to a reactor and stirred at room temperature for 0.5 h. The reaction was monitored by TCL. After the reaction was completed, the mixture was extracted with ethyl acetate and saturated brine. The combined organic phases were subjected to vacuum distillation and separated by column chromatography to obtain the target product 2,4-dibenzyl-6-cyclooctyl-1,2,4-triazine-3,5(2H,4H)-dione, with a yield of 70%.

[0051] The structure of the target product is as follows: .

[0052] The proton NMR spectrum of the target product is shown below. Figure 6 Carbon spectrum Figure 7 The structural characterization data are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 7.49 – 7.46 (m, 2H), 7.41 – 7.38 (m,2H), 7.35 – 7.31 (m, 2H), 7.31 – 7.24 (m, 4H), 5.06 (d, J = 1.5 Hz, 4H), 3.19– 3.10 (m, 1H), 1.78 – 1.67 (m, 6H), 1.63 – 1.53 (m, 8H); 13 C NMR (151 MHz, CDCl3) δ 155.7, 150.3, 148.9, 136.0, 135.9, 129.5, 128.8, 128.7, 128.6, 128.2, 128.0, 55.3, 44.2, 38.0, 29.9, 26.8, 26.3, 25.5.

[0053] Example 4 A method for preparing an alkyluracil derivative includes the following steps: Di-tert-butyl 2,2'-(3,5-dioxo-1,2,4-triazine-2,4(3H,5H)-diyl)diacetate (0.2 mmol), norbornene (0.6 mmol), sodium borohydride (0.9 mmol), ferric nitrate nonahydrate (0.9 mmol), and solvent (a mixture of ethanol and acetonitrile) were added to a reactor and stirred at room temperature for 0.5 h. The reaction was monitored by TCL. After the reaction was completed, the mixture was extracted with ethyl acetate and saturated brine. The combined organic phases were subjected to vacuum distillation and column chromatography to obtain the target product 2,4-dibenzyl-6-((1S,2S,4R)-bicyclo[2.2.1]heptane-2-yl)-1,2,4-triazine-3,5(2H,4H)-dione, with a yield of 72%.

[0054] The structure of the target product is as follows: .

[0055] The proton NMR spectrum of the target product is shown below. Figure 8 Carbon spectrum Figure 9 The structural characterization data are as follows: 1 H NMR (600 MHz, Chloroform-d) δ 7.50 – 7.45 (m, 2H), 7.42 – 7.38 (m,2H), 7.36 – 7.32 (m, 2H), 7.32 – 7.24 (m, 4H), 5.09 – 5.04 (m, 4H), 2.92-2.87(m, 1H), 2.34 – 2.26 (m, 2H), 1.94-1.86 (m, 1H), 1.63 – 1.52 (m, 2H), 1.49-1.44 (m, 1H), 1.42-1.36 (m, 1H), 1.33-1.29 (m, 1H), 1.28-1.24 (m, 1H), 1.08(dd, J = 9.8, 2.9 Hz, 1H); 13 C NMR (151 MHz, CDCl3) δ 156.1, 148.9, 147.9, 135.9, 135.8, 129.5,128.9, 128.7, 128.6, 128.2, 128.0, 55.3, 44.2, 41.9, 41.1, 36.5, 35.4, 33.8,29.8, 29.0. Example 5 A method for preparing an alkyluracil derivative includes the following steps: 2,4-Di(4-bromobenzyl)uracil (0.2 mmol), n-hexene (0.6 mmol), sodium borohydride (0.9 mmol), ferric nitrate nonahydrate (0.9 mmol), and solvent (a mixture of ethanol and acetonitrile) were added to a reactor and stirred at room temperature for 0.5 h. The reaction was monitored by TCL. After the reaction was completed, the mixture was extracted with ethyl acetate and saturated brine. The combined organic phases were subjected to vacuum distillation and column chromatography to obtain the target product S)-2,4-dibenzyl-6-(hexane-2-yl)-1,2,4-triazine-3,5(2H,4H)-dione, with a yield of 85%.

[0056] The structure of the target product is as follows: .

[0057] The structural characterization data of the target product are as follows: 1 H NMR (600 MHz, Chloroform-d) δ 7.49 – 7.45 (m, 2H), 7.41 – 7.36 (m,2H), 7.34 – 7.25 (m, 6H), 5.17 – 4.94 (m, 4H), 3.06 (h, J = 6.9 Hz, 1H),1.74-1.66 (m, 1H), 1.46-1.38 (m, 1H), 1.30 – 1.19 (m, 4H), 1.16 (d, J = 6.9Hz, 3H), 0.86 (t, J = 7.1 Hz, 3H); 13 C NMR (151 MHz, CDCl3) δ 155.9, 149.2, 149.0, 136.0, 135.9, 129.5,128.8, 128.8, 128.7, 128.2, 128.1, 55.3, 44.3, 34.2, 29.5, 22.8, 18.2, 14.2.

[0058] Example 6 A method for preparing an alkyluracil derivative includes the following steps: 2,4-Di(4-chlorobenzyl)uracil (0.2 mmol), n-octene (0.6 mmol), sodium borohydride (0.9 mmol), ferric nitrate nonahydrate (0.9 mmol), and solvent (a mixture of ethanol and acetonitrile) were added to a reactor and stirred at room temperature for 0.5 h. The reaction was monitored by TCL. After the reaction was completed, the mixture was extracted with ethyl acetate and saturated brine. The combined organic phases were subjected to vacuum distillation and column chromatography to obtain the target product S)-2,4-dibenzyl-6-(2-octyl)-1,2,4-triazine-3,5(2H,4H)-dione, with a yield of 79%.

[0059] The structure of the target product is as follows: .

[0060] The structural characterization data of the target product are as follows: 1 H NMR (600 MHz, Chloroform-d) δ 7.48 – 7.43 (m, 2H), 7.41 – 7.37 (m,2H), 7.35 – 7.27 (m, 6H), 5.14 – 5.01 (m, 4H), 3.10-3.02 (m, 1H), 1.73 – 1.65(m, 1H), 1.46 – 1.39 (m, 1H), 1.28 – 1.19 (m, 8H), 1.16 (d, J = 6.9 Hz, 3H), 0.87 (t, J = 7.0 Hz, 3H); 13 C NMR (151 MHz, CDCl3) δ 155.9, 149.2, 149.0, 136.0, 136.0, 129.5,128.8, 128.7, 128.2, 128.1, 55.3, 44.3, 34.5, 34.2, 31.9, 29.5, 27.3, 22.7,18.2, 14.2.

[0061] Example 7 A method for preparing an alkyluracil derivative includes the following steps: 2 benzyl 4 Ethylazuracil (0.2 mmol), styrene (0.6 mmol), sodium borohydride (0.9 mmol), ferric nitrate nonahydrate (0.9 mmol), and solvent (a mixture of ethanol and acetonitrile) were added to a reactor and stirred at room temperature for 0.5 h. The reaction was monitored by TCL. After the reaction was completed, the mixture was extracted with ethyl acetate and saturated brine. The combined organic phases were subjected to vacuum distillation and column chromatography to obtain the target product S)-2,4-dibenzyl-6-(1-phenylpropane-2-yl)-1,2,4-triazine-3,5(2H,4H)-dione, with a yield of 81%.

[0062] The structure of the target product is as follows: .

[0063] The structural characterization data of the target product are as follows: 1 H NMR (600 MHz, Chloroform-d) δ 7.44 – 7.39 (m, 2H), 7.34 – 7.25 (m,8H), 7.20-7.14 (m, 3H), 7.10 – 7.04 (m, 2H), 5.11 – 5.00 (m, 4H), 3.40 (h, J = 7.1 Hz, 1H), 3.03 (dd, J = 13.5, 6.9 Hz, 1H), 2.71 (dd, J = 13.5, 7.8 Hz, 1H), 1.18 (d, J = 6.9 Hz, 3H); 13 C NMR (151 MHz, CDCl3) δ 155.7, 148.8, 148.2, 139.8, 135.9, 135.7,129.3, 129.2, 128.7, 128.6, 128.3, 128.1, 128.0, 126.1, 55.3, 44.2, 40.4, 36.2, 17.9.

[0064] Example 8 A method for preparing an alkyluracil derivative includes the following steps: 2 benzyl 4 (4-methyl)benzyluracil (0.2 mmol), 3-enyl-1-butanol (0.6 mmol), sodium borohydride (0.9 mmol), ferric nitrate nonahydrate (0.9 mmol), and solvent (a mixture of ethanol and acetonitrile) were added to a reactor and stirred at room temperature for 0.5 h. The reaction was monitored by TCL. After the reaction was completed, the mixture was extracted with ethyl acetate and saturated brine. The combined organic phases were subjected to vacuum distillation and column chromatography to obtain the target product S)-2,4-dibenzyl-6-(4-hydroxybutane-2-yl)-1,2,4-triazine-3,5(2H,4H)-dione, with a yield of 80%.

[0065] The structure of the target product is as follows: .

[0066] The structural characterization data of the target product are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 7.50 – 7.43 (m, 2H), 7.41 – 7.36 (m,2H), 7.36 – 7.32 (m, 2H), 7.32 – 7.25 (m, 4H), 5.11 – 5.04 (m, 4H), 3.63-3.58m, 1H), 3.56-3.50 (m, 1H), 3.3-2.5 (m, 1H), 2.05 (s, 1H), 1.87 – 1.83 (m,1H), 1.81-1.74 (m, 1H), 1.21 (d, J = 6.9 Hz, 3H); 13 C NMR (151 MHz, CDCl3) δ 156.3, 148.7, 148.6, 135.8, 135.7, 129.4, 128.7, 128.6, 128.2, 128.1, 60.5, 55.3, 44.3, 38.0, 30.7, 18.2.

[0067] Example 9 A method for preparing an alkyluracil derivative includes the following steps: 2 benzyl 4 (4-Trifluoromethyl)benzyluracil (0.2 mmol), 4-bromo-1-butene (0.6 mmol), sodium borohydride (0.9 mmol), ferric nitrate nonahydrate (0.9 mmol), and solvent (a mixture of ethanol and acetonitrile) were added to a reactor and stirred at room temperature for 0.5 h. The reaction was monitored by TCL. After the reaction was completed, the mixture was extracted with ethyl acetate and saturated brine. The combined organic phases were subjected to vacuum distillation and column chromatography to obtain the target product S)-2,4-dibenzyl-6-(4-bromobutyl-2-yl)-1,2,4-triazine-3,5(2H,4H)-dione, with a yield of 69%.

[0068] The structure of the target product is as follows: .

[0069] The structural characterization data of the target product are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 7.51 – 7.45 (m, 2H), 7.40 – 7.37 (m,2H), 7.36 – 7.25 (m, 6H), 5.15 – 5.00 (m, 4H), 3.38 – 3.30 (m, 2H), 3.30-3.24(m, 1H), 2.35-2.27 (m, 1H), 2.07-1.99 (m, 1H), 1.20 (d, J = 6.9 Hz, 3H); 13 C NMR (151 MHz, CDCl3) δ 155.7, 148.9, 147.5, 135.8, 129.6, 128.9, 128.4, 128.2, 55.3, 44.4, 36.7, 33.4, 30.9, 18.1.

[0070] Example 10 A method for preparing an alkyluracil derivative includes the following steps: 2 (4-methylbenzyl)uracil (0.2 mmol), allyloxybenzene (0.6 mmol), sodium borohydride (0.9 mmol), ferric nitrate nonahydrate (0.9 mmol), and solvent (a mixture of ethanol and acetonitrile) were added to a reactor and stirred at room temperature for 0.5 h. The reaction was monitored by TCL. After the reaction was completed, the mixture was extracted with ethyl acetate and saturated brine. The combined organic phases were subjected to vacuum distillation and column chromatography to obtain the target product R)-2,4-dibenzyl-6-(1-phenoxypropane-2-yl)-1,2,4-triazine-3,5(2H,4H)-dione, with a yield of 87%.

[0071] The structure of the target product is as follows: .

[0072] The structural characterization data of the target product are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 7.50 – 7.41 (m, 2H), 7.36-7.32 (m,2H), 7.31 – 7.20 (m, 8H), 6.92 (t, J = 7.3, 1.1 Hz, 1H), 6.85 – 6.78 (m, 2H), 5.10 – 5.01 (m, 4H), 4.25-4.20 (m, 1H), 4.05-4.0 (m, 1H), 3.61-3.55 (m, 1H), 1.31 (d, J = 7.0 Hz, 3H); 13 C NMR (151 MHz, CDCl3) δ 158.8, 155.7, 148.8, 145.8, 135.7, 129.5, 128.7, 128.7, 128.6, 128.2, 128.1, 120.9, 114.7, 69.7, 55.3, 44.3, 34.8, 15.1.

[0073] Example 11 A method for preparing an alkyluracil derivative includes the following steps: 2 (4-tert-butylbenzyl)uracil (0.2 mmol), allyl methyl carbonate (0.6 mmol), sodium borohydride (0.9 mmol), ferric nitrate nonahydrate (0.9 mmol), and solvent (a mixture of ethanol and acetonitrile) were added to a reactor and stirred at room temperature for 0.5 h. The reaction was monitored by TCL. After the reaction was completed, the mixture was extracted with ethyl acetate and saturated brine. The combined organic phases were subjected to vacuum distillation and column chromatography to obtain the target product R)-2-(2,4-dibenzyl-3,5-dioxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)propyl methyl carbonate in 86% yield.

[0074] The structure of the target product is as follows: .

[0075] The structural characterization data of the target product are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 7.49 – 7.44 (m, 2H), 7.42 – 7.35 (m,2H), 7.35 – 7.25 (m, 6H), 5.07 (s, 2H), 5.07 (s, 2H), 4.38-4.33 (m, 1H), 4.32-4.27 (m, 1H), 3.70 (s, 3H), 3.50-3.42 (m, 1H), 1.24 (d, J = 7.0 Hz, 3H); 13 C NMR (151 MHz, CDCl3) δ 155.7, 148.8, 145.2, 135.7, 129.5, 128.8, 128.8, 128.7, 128.3, 128.1, 69.3, 55.5, 54.9, 44.4, 34.2, 14.9.

[0076] Example 12 A method for preparing an alkyluracil derivative includes the following steps: 2,4-Dibenzyluracil (0.2 mmol), 1-(butyl-3-en-1-yl)-2,3,4,5,6-pentafluorobenzene (0.6 mmol), sodium borohydride (0.9 mmol), ferric nitrate nonahydrate (0.9 mmol), and solvent (a mixture of ethanol and acetonitrile) were added to a reactor and stirred at room temperature for 0.5 h. The reaction was monitored by TCL. After the reaction was completed, the mixture was extracted with ethyl acetate and saturated brine. The combined organic phases were subjected to vacuum distillation and column chromatography to obtain the target product S)-2,4-dibenzyl-6-(4-(perfluorophenyl)butan-2-yl)-1,2,4-triazine-3,5(2H,4H)-dione, with a yield of 70%.

[0077] The structure of the target product is as follows: .

[0078] The structural characterization data of the target product are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 7.44 (d, J = 6.9 Hz, 2H), 7.35-7.25(m, 8H), 5.11 – 5.05 (m, 3H), 5.03-4.97 (m, 1H), 3.49-3.42 (m, 1H), 3.05 (dd, J = 13.9, 6.8 Hz, 1H), 2.97 (dd, J = 13.8, 6.5 Hz, 1H), 1.20 (d, J = 7.0 Hz, 3H); 13 C NMR (151 MHz, CDCl3) δ 155.6, 148.9, 146.6, 135.7, 135.6, 129.4, 128.8, 128.7, 128.6, 128.3, 128.2, 55.3, 44.4, 34.3, 26.8, 17.2. 19 F NMR (565MHz, CDCl3) δ -142.45, -156.13, -162.29.

[0079] Example 13 A method for preparing an alkyluracil derivative includes the following steps: 2,4-Dibenzyluracil (0.2 mmol), 2-(but-3-en-1-ethoxy)isoindol-1,3-dione (0.6 mmol), sodium borohydride (0.9 mmol), ferric nitrate nonahydrate (0.9 mmol), and solvent (a mixture of ethanol and acetonitrile) were added to a reactor and stirred at room temperature for 0.5 h. The reaction was monitored by TCL. After the reaction was completed, the mixture was extracted with ethyl acetate and saturated brine. The combined organic phases were subjected to vacuum distillation and column chromatography to obtain the target product S)-2-(3-(2,4-dibenzyl-3,5-dioxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)butoxy)isoindolin-1,3-dione, with a yield of 70%.

[0080] The structure of the target product is as follows: .

[0081] The structural characterization data of the target product are as follows: 1 H NMR (600 MHz, Chloroform-d) δ 7.79 (dd, J = 5.4, 3.1 Hz, 2H), 7.74 (td, J = 5.1, 2.7 Hz, 2H), 7.51 – 7.45 (m, 2H), 7.40 – 7.35 (m, 2H), 7.29 –7.19 (m, 6H), 5.18 – 5.02 (m, 4H), 4.22-4.16 (m, 1H), 4.14-4.08 (m, 1H), 3.46-3.37 (m, 1H), 2.25-2.17 (m, 1H), 2.08 – 1.99 (m, 1H), 1.27 (d, J = 6.9Hz, 3H); 13 C NMR (151 MHz, CDCl3) δ 168.0, 163.4, 155.8, 149.0, 147.7, 135.9, 135.8, 134.4, 134.3, 132.7, 129.4, 128.9, 128.7, 128.6, 128.5, 128.0, 127.9, 123.6, 123.6, 76.17, 55.2, 44.2, 32.0, 31.3, 18.6.

[0082] Example 14 A method for preparing an alkyluracil derivative includes the following steps: 2,4 Dinaphthylbenzylazuraidine (0.2 mmol), cyclohexene (0.6 mmol), sodium borohydride (0.9 mmol), ferrous nitrate (0.9 mmol), and solvent (a mixture of ethanol and acetonitrile) were added to the reactor and stirred at room temperature for 0.5 h. The reaction was monitored by TCL. After the reaction was completed, the mixture was extracted with ethyl acetate and saturated brine. The combined organic phases were subjected to vacuum distillation and separated by column chromatography (using a mixture of petroleum ether and ethyl acetate as the eluent, with a volume ratio of petroleum ether to ethyl acetate of 15:1) to obtain the target product 6-cyclohexyl-2,4-bis(naphthyl-2-ylmethyl)-1,2,4-triazine-3,5(2H,4H)-dione, with a yield of 40%.

[0083] Example 15 A method for preparing an alkyluracil derivative includes the following steps: 2,4 Dinaphthylbenzylazuraidine (0.2 mmol), cyclohexene (0.6 mmol), sodium borohydride (0.9 mmol), ferric chloride (0.9 mmol), and solvent (a mixture of ethanol and acetonitrile) were added to the reactor and stirred at room temperature for 0.5 h. The reaction was monitored by TCL. After the reaction was completed, the mixture was extracted with ethyl acetate and saturated brine. The combined organic phases were subjected to vacuum distillation and separated by column chromatography (using a mixture of petroleum ether and ethyl acetate as the eluent, with a volume ratio of petroleum ether to ethyl acetate of 15:1) to obtain the target product 6-cyclohexyl-2,4-bis(naphthyl-2-ylmethyl)-1,2,4-triazine-3,5(2H,4H)-dione, with a yield of 35%.

[0084] Example 16 A method for preparing an alkyluracil derivative includes the following steps: 2,4 Dinaphthylbenzylazuraidine (0.2 mmol), cyclohexene (0.6 mmol), sodium borohydride (0.9 mmol), ferrous chloride (0.9 mmol), and solvent (a mixture of ethanol and acetonitrile) were added to the reactor and stirred at room temperature for 0.5 h. The reaction was monitored by TCL. After the reaction was completed, the mixture was extracted with ethyl acetate and saturated brine. The combined organic phases were subjected to vacuum distillation and separated by column chromatography (using a mixture of petroleum ether and ethyl acetate as the eluent, with a volume ratio of petroleum ether to ethyl acetate of 15:1) to obtain the target product 6-cyclohexyl-2,4-bis(naphthyl-2-ylmethyl)-1,2,4-triazine-3,5(2H,4H)-dione, with a yield of 15%.

[0085] Example 17 A method for preparing an alkyluracil derivative includes the following steps: 2,4 Dinaphthylbenzylazuraidine (0.2 mmol), cyclohexene (0.6 mmol), sodium borohydride (0.9 mmol), ferric sulfate (0.9 mmol), and solvent (a mixture of ethanol and acetonitrile) were added to the reactor and stirred at room temperature for 0.5 h. The reaction was monitored by TCL. After the reaction was completed, the mixture was extracted with ethyl acetate and saturated brine. The combined organic phases were subjected to vacuum distillation and separated by column chromatography (using a mixture of petroleum ether and ethyl acetate as the eluent, with a volume ratio of petroleum ether to ethyl acetate of 15:1) to obtain the target product 6-cyclohexyl-2,4-bis(naphthyl-2-ylmethyl)-1,2,4-triazine-3,5(2H,4H)-dione, with a yield of 20%.

[0086] Example 18 A method for preparing an alkyluracil derivative includes the following steps: 2,4 Dinaphthylbenzylazuraidine (0.2 mmol), cyclohexene (0.6 mmol), sodium borohydride (0.9 mmol), ferric oxalate (0.9 mmol), and solvent (a mixture of ethanol and acetonitrile) were added to the reactor and stirred at room temperature for 0.5 h. The reaction was monitored by TCL. After the reaction was completed, the mixture was extracted with ethyl acetate and saturated brine. The combined organic phases were subjected to vacuum distillation and separated by column chromatography (using a mixture of petroleum ether and ethyl acetate as the eluent, with a volume ratio of petroleum ether to ethyl acetate of 15:1) to obtain the target product 6-cyclohexyl-2,4-bis(naphthyl-2-ylmethyl)-1,2,4-triazine-3,5(2H,4H)-dione, with a yield of 30%.

[0087] Example 19 A method for preparing an alkyluracil derivative includes the following steps: 2,4 Dinaphthylbenzylazuraidine (0.2 mmol), cyclohexene (0.6 mmol), lithium borohydride (0.9 mmol), ferric chloride (0.9 mmol), and solvent (a mixture of ethanol and acetonitrile) were added to the reactor and stirred at room temperature for 0.5 h. The reaction was monitored by TCL. After the reaction was completed, the mixture was extracted with ethyl acetate and saturated brine. The combined organic phases were subjected to vacuum distillation and separated by column chromatography (using a mixture of petroleum ether and ethyl acetate as the eluent, with a volume ratio of petroleum ether to ethyl acetate of 15:1) to obtain the target product 6-cyclohexyl-2,4-bis(naphthyl-2-ylmethyl)-1,2,4-triazine-3,5(2H,4H)-dione, with a yield of 60%.

[0088] Example 20 A method for preparing an alkyluracil derivative includes the following steps: 2,4 Dinaphthylbenzylazuraidine (0.2 mmol), cyclohexene (0.6 mmol), lithium aluminum hydride (0.9 mmol), ferric chloride (0.9 mmol), and solvent (a mixture of ethanol and acetonitrile) were added to the reactor and stirred at room temperature for 0.5 h. The reaction was monitored by TCL. After the reaction was completed, the mixture was extracted with ethyl acetate and saturated brine. The combined organic phases were subjected to vacuum distillation and separation by column chromatography (using a mixture of petroleum ether and ethyl acetate as the eluent, with a volume ratio of petroleum ether to ethyl acetate of 15:1) to obtain the target product 6-cyclohexyl-2,4-bis(naphthyl-2-ylmethyl)-1,2,4-triazine-3,5(2H,4H)-dione, with a yield of 20%.

[0089] Example 21 A method for preparing an alkyluracil derivative includes the following steps: 2,4 Dinaphthylbenzylazuraidine (0.2 mmol), cyclohexene (0.6 mmol), triphenylsilane (0.9 mmol), ferric chloride (0.9 mmol), and solvent (a mixture of ethanol and acetonitrile) were added to the reactor and stirred at room temperature for 0.5 h. The reaction was monitored by TCL. After the reaction was completed, the mixture was extracted with ethyl acetate and saturated brine. The combined organic phases were subjected to vacuum distillation and separated by column chromatography (using a mixture of petroleum ether and ethyl acetate as the eluent, with a volume ratio of petroleum ether to ethyl acetate of 15:1) to obtain the target product 6-cyclohexyl-2,4-bis(naphthyl-2-ylmethyl)-1,2,4-triazine-3,5(2H,4H)-dione, with a yield of 10%.

[0090] Example 22 A method for preparing an alkyluracil derivative includes the following steps: 2,4 Dinaphthylbenzylazuraidine (0.2 mmol), cyclohexene (0.6 mmol), triethylsilane (0.9 mmol), ferric chloride (0.9 mmol), and solvent (a mixture of ethanol and acetonitrile) were added to the reactor and stirred at room temperature for 0.5 h. The reaction was monitored by TCL. After the reaction was completed, the mixture was extracted with ethyl acetate and saturated brine. The combined organic phases were subjected to vacuum distillation and separated by column chromatography (using a mixture of petroleum ether and ethyl acetate as the eluent, with a volume ratio of petroleum ether to ethyl acetate of 15:1) to obtain the target product 6-cyclohexyl-2,4-bis(naphthyl-2-ylmethyl)-1,2,4-triazine-3,5(2H,4H)-dione, with a yield of 10%.

[0091] Example 23 A method for preparing an alkyluracil derivative includes the following steps: 2,4 Dinaphthylbenzylazuraidine (0.2 mmol), cyclohexene (0.6 mmol), borane (0.9 mmol), ferric chloride (0.9 mmol), and solvent (a mixture of ethanol and acetonitrile) were added to the reactor and stirred at room temperature for 0.5 h. The reaction was monitored by TCL. After the reaction was completed, the mixture was extracted with ethyl acetate and saturated brine. The combined organic phases were subjected to vacuum distillation and separated by column chromatography (using a mixture of petroleum ether and ethyl acetate as the eluent, with a volume ratio of petroleum ether to ethyl acetate of 15:1) to obtain the target product 6-cyclohexyl-2,4-bis(naphthyl-2-ylmethyl)-1,2,4-triazine-3,5(2H,4H)-dione, with a yield of 15%.

[0092] Comparative Example 1 The only difference between this comparative example and Example 1 is that ferric nitrate nonahydrate is replaced with an equal amount of copper chloride. The remaining steps and parameters are as described in Example 1.

[0093] Compared with Example 1, the drawback of this comparative example is that the target product cannot be obtained.

[0094] Comparative Example 2 The only difference between this comparative example and Example 1 is that ferric nitrate nonahydrate is replaced with an equal amount of nickel chloride. The remaining steps and parameters are as described in Example 1.

[0095] Compared with Example 1, the drawback of this comparative example is that the target product cannot be obtained.

[0096] Comparative Example 3 The only difference between this comparative example and Example 1 is that sodium borohydride is replaced with an equal amount of water; The remaining steps and parameters are as described in Example 1.

[0097] Compared with Example 1, the drawback of this comparative example is that the target product cannot be obtained.

[0098] Comparative Example 4 The only difference between this comparative example and Example 1 is that sodium borohydride is replaced with an equal amount of isopropanol. The remaining steps and parameters are as described in Example 1.

[0099] Compared with Example 1, the drawback of this comparative example is that the target product cannot be obtained.

[0100] Therefore, this invention utilizes olefins as alkyl raw materials, combined with specific catalysts and specific hydrogen sources, and can react at room temperature without light or heat. The reaction time is short, and it has good functional group tolerance. It successfully realizes the hydrogenation and alkylation reaction of olefins with uracil analogs, and achieves the technical effect of constructing a series of alkyluracil derivatives.

[0101] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for preparing an alkyluracil derivative, characterized in that, Includes the following steps: The uracil analogue was subjected to a hydrogenation-alkylation reaction with an olefin under the action of an iron catalyst and a hydrogen source to obtain the alkyluracil derivative. The iron catalyst includes at least one of ferric nitrate nonahydrate, ferrous nitrate, ferric chloride, ferrous chloride, ferric sulfate, and ferric oxalate. The hydrogen source includes at least one of sodium borohydride, lithium borohydride, lithium aluminum hydride, triphenylsilane, triethylsilane, and borane.

2. The preparation method according to claim 1, characterized in that, The uracil analogue is a pharmacologically active uracil group and has the following structure: ； R1 is selected from hydrogen, benzyl, naphthalenebenzyl, alkyl, alkenyl-substituted alkyl, alkynyl-substituted alkyl, or ester-substituted alkyl; R2 is selected from hydrogen, benzyl, naphthalenebenzyl, alkyl, alkenyl-substituted alkyl, alkynyl-substituted alkyl, or ester-substituted alkyl.

3. The preparation method according to claim 1, characterized in that, The olefins include at least one of cyclic olefins and chain olefins; Preferably, the cyclic olefin includes at least one selected from cyclohexene, cyclopentene, and cyclooctene; Preferably, the chain olefin includes at least one selected from hexene, halogen-substituted olefins, alcohol-substituted olefins, ester-substituted olefins, ether-substituted olefins, and phenyl-substituted olefins.

4. The preparation method according to any one of claims 1-3, characterized in that, The iron catalyst is ferric nitrate nonahydrate; Preferably, the hydrogen source is sodium borohydride; Preferably, the solvent used in the hydrogenation alkylation reaction includes at least one of ethanol, acetonitrile, dichloromethane, dimethyl sulfoxide, N,N-dimethylformamide, and N,N-dimethylacetamide; Preferably, the solvent is a mixture of ethanol and acetonitrile; Preferably, the volume ratio of ethanol to acetonitrile is 1:

1.

5. The preparation method according to any one of claims 1-3, characterized in that, The molar ratio of the uracil analog to the olefin is 1:1 to 9; Preferably, the molar ratio of the uracil analog to the olefin is 1:

3.

6. The preparation method according to claim 5, characterized in that, The molar ratio of the uracil analog to the iron catalyst is 1:1 to 9; Preferably, the molar ratio of the uracil analog to the iron catalyst is 1:

4.

7. The preparation method according to claim 6, characterized in that, The molar ratio of the uracil analog to the hydrogen source is 1:1~9; Preferably, the molar ratio of the uracil analog to the hydrogen source is 1:

4.

8. The preparation method according to claim 7, characterized in that, The hydrogenation alkylation reaction is carried out at a temperature of 20°C to 30°C for a time of 0.1 h to 3 h.

9. An alkyluracil derivative, characterized in that, It is prepared by the preparation method according to any one of claims 1-8; The alkyluracil derivative has the following structure: 。 10. The use of an alkyluracil derivative according to claim 9 in pharmaceutical preparation.

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