Process for the preparation of 6-phosphoryl 1,2,4-triazine-3,5(2H,4H)-dione derivatives

Abstract

The application discloses a preparation method of 6-phosphoryl 1,2,4-triazine-3,5(2H,4H)-dione derivatives. The method comprises the following steps: 1,2,4-triazine-3,5(2H,4H)-dione compounds, phosphoryl precursors, oxidants and alkalis are added into a solvent, and the mixture is reacted under an air atmosphere at 0-75 DEG C for 2-18 hours; extraction, washing, filtration or column chromatography purification are carried out; and finally, 6-phosphoryl substituted 1,2,4-triazine-3,5(2H,4H)-dione derivatives are obtained. In the application, oxygen molecules in the air are used as oxidants, and the reaction is carried out at room temperature (25 DEG C); the reagents used are low in price, the reaction condition is mild, and the post-treatment is simple, so that the application is suitable for industrial production.

Description

TECHNICAL FIELD

[0001] The present application relates to a preparation method of 6-phosphoryl 1,2,4-triazine-3,5(2H,4H)-dione derivatives. BACKGROUND

[0002] 1,2,4-triazine-3,5(2H,4H)-dione, also known as 6-azauracil, is a compound in which the carbon atom at position 6 of uracil is replaced by a nitrogen atom, and is an important derivative of uracil. 1,2,4-triazine-3,5-dione derivatives have special physiological and pharmacological activities. In addition, phosphorus-containing heterocyclic compounds have important biological and chemical properties and play an increasingly important role in organic synthesis, medicinal chemistry, material science and other fields. Combining the two will likely create novel and special functional drug molecules.

[0003] However, there is no simple and efficient method for preparing 6-phosphoryl-substituted 1,2,4-triazine-3,5(2H,4H)-dione derivatives, and such compounds can only be obtained by rearrangement reaction as shown in the following formula, and the preparation process of the reactants used in this method is complex, and the compatible functional group types are less (Russian Journal of General Chemistry, 1996, 66(4): 558-563). The synthesis and preparation of 6-phosphoryl-substituted 1,2,4-triazine-3,5(2H,4H)-dione skeleton drug molecules and the study of drug activity are limited. Therefore, it is necessary to explore a simple and convenient method for directly synthesizing 6-phosphoryl 1,2,4-triazine-3,5(2H,4H)-dione derivatives by directly reacting 1,2,4-triazine-3,5(2H,4H)-dione compounds with phosphoryl precursor compounds.

[0004] SUMMARY

[0005] The present application aims to solve the problems existing in the prior art, and provides a preparation method of 6-phosphoryl 1,2,4-triazine-3,5(2H,4H)-dione derivatives. In this method, phosphite or diaryl phosphine oxide compounds are directly reacted with 1,2,4-triazine-3,5(2H,4H)-dione compounds to prepare 6-phosphoryl 1,2,4-triazine-3,5(2H,4H)-dione derivatives, using 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as the preferred base. In the present application, oxygen molecules in the air are used as oxidants, and the reaction is carried out at room temperature (25℃). The reagents used are inexpensive, the reaction conditions are mild, and the post-treatment is simple. This method is suitable for industrial production and can be applied to the post-functionalization of biologically active molecules and drug derivatives, showing the potential practicality of this method.

[0006] The technical scheme of the present application is:

[0007] A preparation method of 6-phosphoryl 1,2,4-triazine-3,5(2H,4H)-dione derivatives, which comprises the following steps:

[0008] 1,2,4-triazine-3,5(2H,4H)-dione compounds, phosphoryl precursors, oxidants, bases are added to the solvent, and reacted at 0-75 degrees Celsius for 2-18 hours under air atmosphere, extracted, washed, filtered or column chromatography purified, and finally 6-phosphoryl substituted 1,2,4-triazine-3,5(2H,4H)-dione derivatives are obtained;

[0009] Among them, the molar ratio is 1,2,4-triazine-3,5(2H,4H)-dione compounds: phosphoryl precursors: oxidants: bases = 1:1-4:1-5:0.00-5 (preferably 0.01-5); the amount of solvent used is 0.5-15 milliliters of solvent per millimole of 1,2,4-triazine-3,5(2H,4H)-dione compounds; when the content of the material is 0, it means that no substance is added; when air is used as the oxidant, the reaction is carried out under open conditions;

[0010] The 1,2,4-triazine-3,5(2H,4H)-dione compounds are:

[0011] Among them, R 1 and R 2 are the same or different, and are hydrogen atoms, methyl groups, ethyl groups, allyl groups, propargyl groups, ethyl acetate, tert-butyl acetate, phenylacetone groups, (2-(trimethylsilyl)ethoxy) methyl groups, furan ribosyl groups, deoxyfuran ribosyl groups, (3-(2-methoxy-4-(3-oxobutyl) phenoxy) propyl) groups, phenyl groups, benzyl groups, and aryl and benzyl groups substituted with methyl groups, ethyl groups, fluorine atoms, chlorine atoms, bromine atoms, trifluoromethyl groups, cyano groups, formyl ethyl ester groups, nitro groups or methoxy groups;

[0012] N2,N4-bis(4-cyanobenzyl)-1,2,4-triazine-3,5(2H,4H)-dione, N2,N4-bis(4-methoxybenzyl)-1,2,4-triazine-3,5(2H,4H)-dione, N2,N4-dimethyl-1,2,4-triazine-3,5(2H,4H)-dione, N2,N4-bis(ethylacetate)-1,2,4-triazine-3,5(2H,4H)-dione, N2,N4-bis(tert-butylacetate)-1,2,4-triazine-3,5(2H,4H)-dione, N2-phenyl-N4-methyl-1,2,4-triazine-3,5(2H,4H)-dione, N2-(4-methylphenyl)-N4-methyl-1,2,4-triazine-3,5(2H,4H)-dione, N2-(4-ethylphenyl)-N4-methyl-1,2,4-triazine-3,5(2H,4H)-dione, N2-(4-fluorophenyl)-N4-methyl-1,2,4-triazine-3,5(2H,4H)-dione, N2-(4-bromophenyl)-N4-methyl-1,2,4-triazine-3,5(2H,4H)-dione, N2-(4-allyl)-N4-methyl-1,2,4-triazine-3,5(2H,4H)-dione, N2-(4-allyl)-N4-methyl-1,2,4-triazine-3,5(2H,4H)-dione, N2-(O 3′ 5′ 2′ 3′ 5′ N2-(O 3 4 N2-(O 1 2 3 wherein R 4 and R 1 are the same or different, and are phenyl, 4-methoxyphenyl, 4-methylphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, methoxy, ethoxy, isopropoxy. 31 1 ​​​​Specifically, diphenylphosphine oxide, bis(4-methoxyphenyl)phosphine oxide, bis(4-methylphenyl)phosphine oxide, bis(4-fluorophenyl)phosphine oxide, bis(4-chlorophenyl)phosphine oxide, bis(4-bromophenyl)phosphine oxide, methyl phenylphosphinate, ethyl phenylphosphinate or isopropyl phenylphosphinate.

[0016] The oxidizing agent includes iodobenzene di(trifluoroacetate), iodobenzene diacetate, tert-butyl hydroperoxide, cumene hydroperoxide, tert-butyl peroxybenzoate, di-tert-butyl peroxide, dicumyl peroxide, benzoyl peroxide, peroxyacetic acid, m-chloroperbenzoic acid, hydrogen peroxide, potassium peroxodisulfate, sodium peroxodisulfate, ammonium peroxodisulfate, potassium peroxymonosulfate, oxygen, air;

[0017] The base is cesium carbonate, potassium carbonate, sodium carbonate, lithium carbonate, cesium hydroxide, potassium hydroxide, sodium hydroxide, lithium hydroxide, cesium acetate, potassium acetate, sodium acetate, lithium acetate, potassium phosphate, dipotassium hydrogen phosphate, monopotassium phosphate, cesium bicarbonate, potassium bicarbonate, sodium bicarbonate, lithium bicarbonate, triethylamine, diethylamine, n-butylamine, pyridine, morpholine, pyrrolidine, piperidine, piperazine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,4-diazabicyclo[2.2.2]octane, or no base.

[0018] The solvent is acetonitrile, propionitrile, dichloromethane, 1,2-dichloroethane, ethyl acetate, acetone, toluene, trifluorotoluene, methanol, ethanol, isopropanol, tetrahydrofuran, 1,4-dioxane, tetrahydropyran, 1,3-dioxolane, diethyl ether, dibutyl ether, methyl tert-butyl ether, dimethyl carbonate, methylcyclopentyl ether, 1,2-dimethoxyethane, N,N-dimethylformamide or dimethyl sulfoxide.

[0019] The beneficial effects of the present application are:

[0020] The present application introduces phosphoryl group at 6th position of 1,2,4-triazine-3,5(2H,4H)-dione by oxidative cross-dehydrogenative coupling reaction of 1,2,4-triazine-3,5(2H,4H)-dione with phosphoryl precursor compound, and the by-product is water molecule, which has high atom and step economy. The reaction does not need noble metal catalyst, uses degradable dimethyl carbonate as solvent, and has advantages of environmental protection and sustainability; air is used as green oxidant without additional addition of oxidant; the reaction condition is mild, and the functional group has good compatibility, and 1,2,4-triazine-3,5(2H,4H)-dione and various phosphoryl precursors substituted by aryl, benzyl, allyl, propargyl and alkoxycarbonylmethyl are all suitable for the method. The reaction can be applied to modification of 6-azauracil glycoside compound and post-functionalization of gingerone derivative, and provides a synthesis scheme for exploring 1,2,4-triazine-3,5(2H,4H)-dione skeleton as biomolecular probe or bioactive molecule. In addition, most of the reaction products are azaheteroaryl phosphine oxides, which can be reduced to azaheteroaryl phosphine ligands and applied to the field of organic synthesis. DETAILED DESCRIPTION

[0021] The method uses 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as a preferred base, oxygen molecules in air as a preferred oxidant, and 1,2,4-triazine-3,5(2H,4H)-dione to react with a phosphoryl precursor to directly introduce a phosphoryl group at the 6th position. The reagent used in the present application is low in price, the reaction condition is mild, and the post-treatment is simple, and the method is suitable for industrial production (as shown in the following reaction formula).

[0022]

[0023] Synthesis of 6-phosphoryl substituted 1,2,4-triazine-3,5(2H,4H)-dione derivatives

[0024] The method of the present application is further described below in conjunction with specific examples, but the present application is not limited in the scope of the examples. The experimental methods not specified in the following examples are selected according to conventional methods and conditions, or according to the instructions of the commercial product.

[0025] Example 1:

[0026]

[0027] 15 ml of reaction tube is added with substrate N2,N4-dibenzyl-1,2,4-triazine-3,5(2H,4H)-dione (58.6 mg, 0.2 mmol, R 1 , R 2diphenylphosphine oxide (101.1 mg, 0.5 mmol) (R 3 and R 4 are both phenyl groups) and a magnetic stir bar. DBU (60.9 mg, 0.4 mmol) and 1 mL of DMC were added via syringe. The reaction was stirred open to air at room temperature for 12 hours (the reaction was considered to be in excess of oxygen at this point as it was open to air flow). TLC indicated that the reaction was substantially complete. The DMC was removed by rotary evaporation and the crude product was extracted with ethyl acetate and water three times. The organic phases were combined and dried over anhydrous Na2S04. The resulting mixture was then concentrated under reduced pressure and washed with n-hexane, filtered and oven dried to yield the product N2,N4-dibenzyl-6-(diphenylphosphoryl)-1,2,4-triazine-3,5(2H,4H)-dione 96.1 mg, 97% overall yield.

[0028]

[0029] The hydrogen nuclear magnetic resonance spectral data of the resulting product is 1 H NMR (400 MHz, CDC13) δ: 7.82-7.78 (m, 4H), 7.63-7.60 (m, 2H), 7.54-7.50 (m, 4H), 7.44 (s, 2H), 7.34-7.30 (m, 6H), 7.22-7.20 (m, 2H), 5.05 (s, 2H), 5.03 (s, 2H); 31 P NMR (162 MHz, CDC13) δ: 22.8 (s), consistent with the structure.

[0030] Example 2:

[0031]

[0032] A 15 mL reaction tube was charged with the substrate N2,N4-bis(4- fluorobenzyl)-1,2,4-triazine-3,5(2H,4H)-dione (65.8 mg, 0.2 mmol, R 1 , R 2To a solution of N2,N4-bis(4-chlorobenzyl)-6-(diphenylphosphoryl)- 1,2,4-triazine-3,5(2H,4H)-dione (80.3 mg, 0.15 mmol) in 1 mL of DCM was added DBU (12.3 mg, 0.08 mmol) and 1 mL of DMC. The reaction mixture was stirred at room temperature for 12 h. The reaction was monitored by TLC. The solvent was removed under reduced pressure and the residue was extracted with ethyl acetate and water three times. The organic phase was combined and dried over anhydrous Na2SO4. The resulting mixture was concentrated under reduced pressure and washed with n-hexane, filtered, and oven dried to give the product N2,N4-bis(4-chlorobenzyl)-6-(diphenylphosphoryl)- 1,2,4-triazine-3,5(2H,4H)-dione 80.3 mg, 72% overall yield.

[0033]

[0034] The hydrogen nuclear magnetic resonance spectral data of the resulting product is 1 H NMR (400 MHz, CDC13) δ: 7.78-7.73 (m, 4H), 7.62-7.58 (m, 2H), 7.51-7.48 (m, 4H), 7.42-7.39 (m, 2H), 7.15-7.12 (m, 2H), 7.79 (q, J = 8.0 Hz, 4H), 4.98 (s, 2H), 4.95 (s, 2H); 31 P NMR (162 MHz, CDC13) δ: 22.9 (s), consistent with the structure.

[0035] Example 3:

[0036]

[0037] A 15 mL reaction tube was charged with the substrate N2,N4-bis(4- chlorobenzyl)-1,2,4-triazine-3,5(2H,4H)-dione (72.2 mg, 0.2 mmol, R 1 , R 2 = 4-chlorobenzyl), diphenylphosphine oxide (101.1 mg, 0.5 mmol), and a magnetic stir bar. DBU (60.9 mg, 0.4 mmol) and 1 mL of DMC were added via syringe. The reaction was stirred at room temperature open to the air (at this point the reaction is open to air flow, which is considered an excess of oxygen) for 12 h. The reaction was monitored by TLC. The DMC was removed by rotary evaporation, and the crude product was extracted with ethyl acetate and water three times. The organic phase was combined and dried over anhydrous Na2SO4. The resulting mixture was concentrated under reduced pressure and washed with n-hexane, filtered, and oven dried to give the product N2,N4-bis(4-chlorobenzyl)-6-(diphenylphosphoryl)- 1,2,4-triazine-3,5(2H,4H)-dione 80.3 mg, 72% overall yield.

[0038]

[0039] The hydrogen nuclear magnetic resonance spectrum data of the product obtained is 1 H NMR (400 MHz, CDCI3) δ: 7.72-7.67 (m, 4H), 7.57-7.53 (m, 2H), 7.46-7.42 (m, 4H), 7.29 (d, J = 8.0 Hz, 2H), 7.21-7.17 (m, 4H), 7.03 (d, J = 8.0 Hz, 2H), 4.92 (s, 2H), 4.89 (s, 2H); 31 P NMR (162 MHz, CDCI3) δ: 22.9 (s), consistent with the structural formula.

[0040] Example 4:

[0041]

[0042] Into a 15 mL reaction tube was added the substrate N2,N4-bis(4- cyanobenzyl)-1,2,4-triazine-3,5(2H,4H)-dione (68.6 mg, 0.2 mmol, the substituent R 1 , R 2 is 4-cyanobenzyl), diphenyl phosphine oxide (101.1 mg, 0.5 mmol) and a magnetic stir bar. DBU (60.9 mg, 0.4 mmol) and 1 mL of DMC were added via syringe. The reaction was stirred at room temperature open to the air for 12 hours (the reaction was open to air, which was considered excess oxygen). TLC indicated that the reaction was substantially complete. The DMC was evaporated by rotary evaporation and the crude product was extracted with ethyl acetate and water three times. The organic phases were combined and dried over anhydrous Na2SO4. The resulting mixture was then concentrated under reduced pressure and washed with n-hexane, filtered and oven dried to yield the product N2,N4-bis(4-cyanobenzyl)-6-(diphenylphosphoryl)-1,2,4-triazine-3,5(2H,4H)-dione 55.7 mg, 51% overall yield.

[0043]

[0044] The hydrogen nuclear magnetic resonance spectrum data of the product obtained is 1 H NMR (400 MHz, CDCI3) δ: 7.79-7.74 (m, 4H), 7.64 (t, J = 8.0 Hz, 2H), 7.59-7.49 (m, 11H), 7.28 (s, 1H), 5.08 (s, 2H), 5.03 (s, 2H); 31 P NMR (162 MHz, CDCI3) δ: 23.0 (s), consistent with the structural formula.

[0045] Example 5:

[0046]

[0047] A 15 mL reaction tube was charged with the substrate N2,N4-bis(4- methoxybenzyl)-1,2,4-triazine-3,5(2H,4H)-dione (70.6 mg, 0.2 mmol, R 1 , R 2 = 4-methoxybenzyl), diphenyl phosphorochloridate (101.1 mg, 0.5 mmol) and a magnetic stir bar. DBU (60.9 mg, 0.4 mmol) and 1 mL of DMC were added via syringe. The reaction was stirred open to the air at room temperature for 12 h (the reaction was considered to be in excess of oxygen as it was open to air flow). TLC indicated that the reaction was substantially complete. The DMC was removed by rotary evaporation and the crude product was extracted with ethyl acetate and water three times. The organic phases were combined and dried over anhydrous Na2S04. The resulting mixture was then concentrated under reduced pressure and washed with n-hexane, filtered and oven dried to yield the product N2,N4-bis(4-methoxybenzyl)-6-(diphenylphosphoryl)-1,2,4-triazine-3,5(2H,4H)-dione 90.3 mg, 82% overall yield.

[0048]

[0049] The product had the following hydrogen nuclear magnetic resonance spectral data 1 H NMR (400 MHz, CDCI3) δ: 7.79-7.74 (m, 4H), 7.60-7.57 (m, 2H), 7.50-7.47 (m, 4H), 7.37 (d, J = 8.0 Hz, 2H), 7.1 1 (d, J = 8.0 Hz, 2H), 6.81 -6.77 (m, 4H), 4.95 (s, 2H), 4.93 (s, 2H), 3.79 (s, 3H), 3.76 (s, 3H); 31 P NMR (162 MHz, CDCI3) δ: 22.9 (s), consistent with the structure.

[0050] Example 6:

[0051]

[0052] A 15 mL reaction tube was charged with the substrate N2,N4-bis(4- methoxybenzyl)-1,2,4-triazine-3,5(2H,4H)-dione (70.6 mg, 0.2 mmol, R 1 , R 2The reaction mixture consisted of methyl diphenylphosphine (101.1 mg, 0.5 mmol), diphenylphosphine (60.9 mg, 0.4 mmol), and magnetic flux. DBU and 1 mL of DMC were added using a syringe. The mixture was stirred in an open atmosphere at room temperature for 12 hours (the reaction was considered to be in excess oxygen). Thin-layer chromatography confirmed the reaction was nearly complete. DMC was removed by rotary evaporation, and the crude product was extracted three times with ethyl acetate and water. The combined organic phases were dried over anhydrous Na₂SO₄. The resulting mixture was then concentrated under reduced pressure, washed with n-hexane, filtered, and dried to give 50.4 mg of the product N₂,N₄-dimethyl-6-(diphenylphospho)-1,2,4-triazine-3,5(2H,4H)-dione, with an overall yield of 74%.

[0053]

[0054] The hydrogen atomic nuclear magnetic resonance spectrum data of the obtained product are as follows: 1 H NMR(400MHz, CDCl3)δ:7.87–7.82(m,4H),7.58–7.55(m,2H),7.49–7.46(m,4H),3.69(s,3H),3.27(s,3H); 31 P NMR (162MHz, CDCl3) δ: 21.5 (s), consistent with the structural formula.

[0055] Example 7:

[0056]

[0057] The substrate N2,N4-bis(ethyl acetate)-1,2,4-triazine-3,5(2H,4H)-dione (57 mg, 0.2 mmol, substituent R in the structural formula) was added to a 15 mL reaction tube. 1 R 2 Ethyl acetate (ethyl acetate), diphenylphosphine (101.1 mg, 0.5 mmol), and magnetic flux were added, along with DBU (60.9 mg, 0.4 mmol) and 1 mL of DMC using a syringe. The mixture was stirred in an open atmosphere at room temperature for 12 hours (the reaction was considered to be in excess oxygen). Thin-layer chromatography showed that the reaction was essentially complete. DMC was removed by rotary evaporation, and the crude product was extracted three times with ethyl acetate and water. The combined organic phases were dried over anhydrous Na₂SO₄. The resulting mixture was then concentrated under reduced pressure, washed with n-hexane, filtered, and dried to give 72.2 mg of the product N₂,N₄-bis(ethyl acetate)-6-(diphenylphosphine)-1,2,4-triazine-3,5(2H,4H)-dione, with an overall yield of 74%.

[0058]

[0059] The hydrogen nuclear magnetic resonance spectrum data of the product obtained is 1 H NMR (400 MHz, CDCI3) δ: 7.86-7.81 (m, 4H), 7.60-7.56 (m, 2H), 7.51-7.47 (m, 4H), 4.78 (s, 2H), 4.58 (s, 2H), 4.26-4.15 (m, 4H), 1.28 (t, J = 8.0 Hz, 3H), 1.23 (t, J = 8.0 Hz, 3H); 31 P NMR (162 MHz, CDCI3) δ: 21.6 (s), consistent with the structural formula.

[0060] Example 8:

[0061]

[0062] Into a 15 mL reaction tube was added the substrate N2,N4-bis(tert- butyl acetate)-1,2,4-triazine-3,5(2H,4H)-dione (68.2 mg, 0.2 mmol, the substituent R 1 , R 2 is tert-butyl acetate), diphenyl phosphine oxide (101.1 mg, 0.5 mmol) and a magnetic stir bar. DBU (60.9 mg, 0.4 mmol) and 1 mL of DMC were added via syringe. The reaction was stirred at room temperature open to the air for 12 hours (the reaction was open to the air, and the air was considered excess oxygen). TLC indicated that the reaction was substantially complete. The DMC was evaporated by rotary evaporation, and the crude product was extracted with ethyl acetate and water three times. The organic phases were combined and dried over anhydrous Na2SO4. The resulting mixture was then concentrated under reduced pressure and washed with n-hexane, filtered, and oven dried to obtain the product N2,N4-bis(tert-butyl acetate)-6-(diphenyl phosphoroyl)-1,2,4-triazine-3,5(2H,4H)-dione 86.7 mg, total yield 80%.

[0063]

[0064] The hydrogen nuclear magnetic resonance spectrum data of the product obtained is 1 H NMR (400 MHz, CDCI3) δ: 7.86-7.81 (m, 4H), 7.58-7.55 (m, 2H), 7.49-7.45 (m, 4H), 4.67 (s, 2H), 4.47 (s, 2H), 1.45 (s, 9H), 1.40 (s, 9H); 31 P NMR (162 MHz, CDCI3) δ: 21.5 (s), consistent with the structural formula.

[0065] Example 9:

[0066]

[0067] 15 mL reaction tube was charged with the substrate N2-phenyl-N4-methyl-1,2,4-triazine- 3,5(2H,4H)-dione (40.6 mg, 0.2 mmol, R in the structure above is phenyl, R 1 is phenyl, R 2 is methyl), diphenylphosphoryl chloride (101.1 mg, 0.5 mmol) and a magnetic stir bar. DBU (60.9 mg, 0.4 mmol) and 1 mL of DMC were added via syringe. The reaction was stirred open to the air at room temperature for 12 h. TLC indicated that the reaction was substantially complete. The DMC was removed by rotary evaporation and the crude product was extracted with ethyl acetate and water three times. The organic phases were combined and dried over anhydrous Na2SO4. The resulting mixture was then concentrated under reduced pressure and washed with n-hexane, filtered, and oven dried to yield the product N2-phenyl-N4-methyl-6-(diphenylphosphoryl)-1,2,4-triazine-3,5(2H,4H)-dione 71.3 mg, 88% overall yield.

[0068]

[0069] The hydrogen nuclear magnetic resonance spectral data of the product obtained is 1 H NMR (400 MHz, CDC13) δ: 7.92 - 7.87 (m, 4H), 7.59 - 7.55 (m, 2H), 7.50 - 7.44 (m, 7H), 7.17 (d, J = 4.0 Hz, 2H), 3.76 (s, 3H); 31 P NMR (162 MHz, CDC13) δ: 21.2 (s), consistent with the structure.

[0070] Example 10:

[0071]

[0072] 15 mL reaction tube was charged with the substrate N2-(4-methylphenyl)-N4-methyl-1,2,4- triazine-3,5(2H,4H)-dione (43.4 mg, 0.2 mmol, R in the structure above is 4-methylphenyl, R 1 is 4-methylphenyl, R 2The reaction mixture consisted of methyl phosphonium bicarbonate (101.1 mg, 0.5 mmol), diphenylphosphine (60.9 mg, 0.4 mmol), and magnetic flux. DBU and 1 mL of DMC were added using a syringe. The mixture was stirred in an open atmosphere at room temperature for 12 hours (the reaction was considered to be in excess oxygen). Thin-layer chromatography confirmed the reaction was nearly complete. DMC was removed by rotary evaporation, and the crude product was extracted three times with ethyl acetate and water. The combined organic phases were dried over anhydrous Na₂SO₄. The resulting mixture was then concentrated under reduced pressure, washed with n-hexane, filtered, and dried to give 78.2 mg of the product N₂-(4-methylphenyl)-N₄-methyl-6-(diphenylphosphoyl)-1,2,4-triazine-3,5(2H,4H)-dione, with an overall yield of 94%.

[0073]

[0074] The hydrogen atomic nuclear magnetic resonance spectrum data of the obtained product are as follows: 1 H NMR(400MHz, CDCl3)δ:7.93–7.88(m,4H),7.58–7.55(m,2H),7.50–7.46(m, 4H),7.25(d,J=8.0Hz,2H),7.04(d,J=8.0Hz,2H),3.75(s,3H),2.35(s,3H); 31 P NMR (162MHz, CDCl3) δ: 21.2 (s), consistent with the structural formula.

[0075] Example 11:

[0076]

[0077] Add the substrate N2-(4-ethylphenyl)-N4-methyl-1,2,4-triazine-3,5(2H,4H)-dione (46.2 mg, 0.2 mmol, substituent R in the structural formula) to a 15 mL reaction tube. 1 It is 4-ethylphenyl, R 2 The reaction mixture consisted of methyl hydroxyl (4-ethylphenyl)-N4-methyl-6-(diphenylphosphoyl)-1,2,4-triazine-3,5(2H,4H)-dione (101.1 mg, 0.5 mmol) and a magnetic flux. DBU (60.9 mg, 0.4 mmol) and 1 mL of DMC were added using a syringe. The mixture was stirred in an open atmosphere at room temperature for 12 hours (with air circulation, considered as oxygen in excess). Thin-layer chromatography confirmed the reaction was nearly complete. DMC was removed by rotary evaporation, and the crude product was extracted three times with ethyl acetate and water. The combined organic phases were dried over anhydrous Na2SO4. The resulting mixture was then concentrated under reduced pressure, washed with n-hexane, filtered, and dried to give 79.7 mg of N2-(4-ethylphenyl)-N4-methyl-6-(diphenylphosphoyl)-1,2,4-triazine-3,5(2H,4H)-dione, with an overall yield of 92%.

[0078]

[0079] The hydrogen nuclear magnetic resonance spectrum data of the product obtained is 1 H NMR (400 MHz, CDCI3) δ: 7.93-7.88 (m, 4H), 7.58-7.55 (m, 2H), 7.50-7.46 (m, 4H), 7.28 (d, J = 12.0 Hz, 2H), 7.07 (d, J = 8.0 Hz, 2H), 3.76 (s, 3H), 2.66 (q, J = 8.0 Hz, 2H), 1.22 (t, J = 8.0 Hz, 3H); 31 P NMR (162 MHz, CDCI3) δ: 21.1 (s), consistent with the structure.

[0080] Example 12:

[0081]

[0082] Into a 15 mL reaction tube was added the substrate N2-(4-fluorophenyl)-N4-methyl- 1,2,4-triazine-3,5(2H,4H)-dione (442 mg, 0.2 mmol, R 1 is 4-fluorophenyl, R 2 is methyl), diphenyl phosphine oxide (101.1 mg, 0.5 mmol) and a magnetic stir bar. DBU (60.9 mg, 0.4 mmol) and 1 mL of DMC were added via syringe. The reaction was stirred open to the air at room temperature for 12 hours (the reaction was open to air, which was considered an excess of oxygen). TLC indicated that the reaction was substantially complete. The DMC was evaporated by rotary evaporation and the crude product was extracted with ethyl acetate and water three times. The organic phases were combined and dried over anhydrous Na2SO4. The resulting mixture was then concentrated under reduced pressure and washed with n-hexane, filtered, and oven dried to yield the product N2-(4-fluorophenyl)-N4-methyl-6-(diphenylphosphoryl)- 1,2,4-triazine-3,5(2H,4H)-dione 75.8 mg, 90% overall yield.

[0083]

[0084] The hydrogen nuclear magnetic resonance spectrum data of the product obtained is 1 H NMR (400 MHz, CDCI3) δ: 7.91-7.86 (m, 4H), 7.60-7.56 (m, 2H), 7.50-7.47 (m, 4H), 7.16-7.11 (m, 4H), 3.74 (s, 3H); 31 P NMR (162 MHz, CDCI3) δ: 21.3 (s), consistent with the structure.

[0085] Example 13:

[0086]

[0087] A 15 mL reaction tube was charged with the substrate N2-(4- bromophenyl)-N4-methyl-1,2,4-triazine-3,5(2H,4H)-dione (56.2 mg, 0.2 mmol, R 1 is 4-bromophenyl, R 2 is methyl), diphenyl phosphorochloridate (101.1 mg, 0.5 mmol), and a magnetic stir bar. DBU (60.9 mg, 0.4 mmol) and 1 mL of DMC were added via syringe. The reaction was stirred open to the air at room temperature for 12 hours (the reaction was considered to be in excess of oxygen as it was open to air flow). TLC indicated that the reaction was substantially complete. The DMC was removed by rotary evaporation and the crude product was extracted with ethyl acetate and water three times. The organic phases were combined and dried over anhydrous Na2SO4. The resulting mixture was then concentrated under reduced pressure and washed with n-hexane, filtered, and oven dried to yield the product N2-(4-bromophenyl)-N4-methyl-6-(diphenylphosphoryl)-1,2,4-triazine-3,5(2H,4H)-dione 89.3 mg, 93% overall yield.

[0088]

[0089] The hydrogen nuclear magnetic resonance spectral data of the product obtained is 1 H NMR (400 MHz, CDC13) δ: 7.91 - 7.86 (m, 4H), 7.58 - 7.57 (m, 4H), 7.51 - 7.47 (m, 4H), 7.05 (d, J = 8.0 Hz, 2H), 3.75 (s, 3H); 31 P NMR (162 MHz, CDC13) δ: 21.2 (s), consistent with the structure.

[0090] Example 14:

[0091]

[0092] A 15 mL reaction tube was charged with the substrate N2-(4- bromophenyl)-N4-methyl-1,2,4-triazine-3,5(2H,4H)-dione (56.2 mg, 0.2 mmol, R 1 is 4-bromophenyl, R 2The reaction mixture consisted of methyl hydroxyl (4-methyl), diphenylphosphine (101.1 mg, 0.5 mmol), and magnetic flux. DBU (60.9 mg, 0.4 mmol) and 1 mL of DMC were added using a syringe. The mixture was stirred in an open atmosphere at room temperature for 12 hours (the reaction was considered to be in excess oxygen). Thin-layer chromatography confirmed that the reaction was nearly complete. DMC was removed by rotary evaporation, and the crude product was extracted three times with ethyl acetate and water. The combined organic phases were dried over anhydrous Na₂SO₄. The resulting mixture was then concentrated under reduced pressure, washed with n-hexane, filtered, and dried to give 69.0 mg of N₂-(4-allyl)-N₄-methyl-6-(diphenylphosphine)-1,2,4-triazine-3,5(2H,4H)-dione, with an overall yield of 94%.

[0093]

[0094] The hydrogen atomic nuclear magnetic resonance spectrum data of the obtained product are as follows: 1 H NMR(400MHz, CDCl3)δ:7.87–7.82(m,4H),7.59–7.55(m,2H),7.51–7.47(m,4 H),5.83–5.73(m,1H),5.29–5.19(m,4H),4.45(d,J=4.0Hz,2H),3.68(s,3H); 31 P NMR (162MHz, CDCl3) δ: 21.6 (s); consistent with the structural formula.

[0095] Example 15:

[0096]

[0097] Add the substrate N2-(4-allyl)-N4-methyl-1,2,4-triazine-3,5(2H,4H)-dione (33.0 mg, 0.2 mmol, substituent R in the structural formula) to a 15 mL reaction tube. 1 It is 4-propynyl, R 2 The reaction mixture consisted of methyl hydroxyl (4-propyl)-N4-methyl-6-(diphenylphosphoyl)-1,2,4-triazine-3,5(2H,4H)-dione (69.3 mg), diphenylphosphine (101.1 mg, 0.5 mmol), and magnetic flux. DBU (60.9 mg, 0.4 mmol) and 1 mL DMC were added using a syringe. The mixture was stirred in an open atmosphere at room temperature for 12 hours (with air circulation, considered as oxygen in excess). Thin-layer chromatography confirmed the reaction was nearly complete. DMC was removed by rotary evaporation, and the crude product was extracted three times with ethyl acetate and water. The combined organic phases were dried over anhydrous Na2SO4. The resulting mixture was then concentrated under reduced pressure, washed with n-hexane, filtered, and dried to give 69.3 mg of N2-(4-propynyl)-N4-methyl-6-(diphenylphosphoyl)-1,2,4-triazine-3,5(2H,4H)-dione, with an overall yield of 95%.

[0098]

[0099] The hydrogen nuclear magnetic resonance spectrum data of the product obtained is 1 H NMR (400 MHz, CDC13) δ: 7.88-7.83 (m, 4H), 7.60-7.56 (m, 2H), 7.51-7.47 (m, 4H), 4.60 (s, 2H), 3.71 (s, 3H), 2.19-2.17 (m, 1H); 31 P NMR (162 MHz, CDC13) δ: 21.4 (s), consistent with the structure.

[0100] Example 16:

[0101]

[0102] Into a 15 mL reaction tube was added the substrate N2-(O 3′ ,O 5′ - bis-p-methylbenzoyl-2'-deoxyribosyl)-N4-methyl-1,2,4-triazine-3,5(2H,4H)-dione (95.8 mg, 0.2 mmol, the substituent R 1 in the structure is O 3′ ,O 5′ - bis-p-methylbenzoyl-2'-deoxyribosyl, R 2 is methyl), diphenyl phosphine oxide (101.1 mg, 0.5 mmol) and a magnet. DBU (60.9 mg, 0.4 mmol) and 1 mL of DMC were added by syringe. The reaction was stirred at room temperature open to the air for 12 hours (the reaction was open to the air at this time, and the air was considered to be in excess of oxygen). TLC detection showed that the reaction was substantially complete. The DMC was evaporated by rotary evaporation, and the crude product was extracted with ethyl acetate and water three times. The organic phase was combined and dried with anhydrous Na2S04. Then the obtained mixture was concentrated under reduced pressure and washed with n-hexane, filtered and dried to obtain the product N2-(O 3′ ,O 5′ - bis-p-methylbenzoyl-2'-deoxyribosyl)-N4-methyl-6-(diphenyl phosphoryl)-1,2,4-triazine-3,5(2H,4H)-dione 112.6 mg, total yield 83%.

[0103]

[0104] The hydrogen nuclear magnetic resonance spectrum data of the product obtained is 1H NMR (400 MHz, CDC13) δ: 7.94 - 7.89 (m, 6H), 7.84 - 7.79 (m, 2H), 7.60 - 7.51 (m, 6H), 7.22 (t, J = 8.0 Hz, 4H), 6.67 (t, J = 8.0 Hz, 1H), 4.81 - 4.77 (m, 1H), 4.40 - 4.36 (m, 1H), 4.13 - 4.08 (m, 1H), 3.90 - 3.86 (m, 1H), 3.31 (s, 3H), 2.67 - 2.60 (m, 1H), 2.43 - 2.36 (m, 7H); 31 P NMR (162 MHz, CDC13) δ: 24.2 (s), consistent with the structure.

[0105] Example 17:

[0106]

[0107] Into a 15 mL reaction tube was added the substrate N2,N4-dibenzyl-1,2,4-triazine-3,5(2H,4H)-dione (58.6 mg, 0.2 mmol, R 1 , R 2 is benzyl), bis(4-methoxyphenyl)phosphine oxide (131.0 mg, 0.5 mmol), and a magnetic stir bar. DBU (60.9 mg, 0.4 mmol) and 1 mL of DMC were added via syringe. The reaction was stirred open to the air at room temperature for 12 hours (the reaction was open to air flow, which was considered an excess of oxygen). The reaction was determined to be substantially complete by thin layer chromatography. The DMC was removed by rotary evaporation, and the crude product was extracted with ethyl acetate and water three times. The organic phases were combined and dried over anhydrous Na2S04. The resulting mixture was then concentrated under reduced pressure and washed with n-hexane, filtered, and oven dried to yield the product N2,N4-dibenzyl-6-(bis(4-methoxyphenyl)phosphine oxide-1,2,4-triazine-3,5(2H,4H)-dione 99.2 mg, 90% overall yield.

[0108]

[0109] The hydrogen nuclear magnetic resonance spectral data for the resulting product was 1 H NMR (400 MHz, CDC13) δ: 7.70 - 7.65 (m, 4H), 7.41 - 7.39 (m, 2H), 7.31 - 7.23 (m, 8H), 6.97 (d, J = 8.0 Hz, 4H), 5.04 (s, 2H), 4.99 (s, 2H), 3.86 (s, 6H); 31 P NMR (162 MHz, CDC13) δ: 22.7 (s), consistent with the structure.

[0110] Example 18:

[0111]

[0112] Into a 15 mL reaction tube was added the substrate N2,N4-dibenzyl-1,2,4-triazine- 3,5(2H,4H)-dione (58.6 mg, 0.2 mmol, R 1 , R 2 = benzyl), bis(4-methylphenyl)phosphine oxide (115.0 mg, 0.5 mmol), and a magnetic stir bar. DBU (60.9 mg, 0.4 mmol) and 1 mL of DMC were added via syringe. The reaction was stirred open to the air at room temperature for 12 h (the reaction was considered to be in excess of oxygen as it was open to air flow). TLC indicated that the reaction was substantially complete. The DMC was removed by rotary evaporation and the crude product was extracted with ethyl acetate and water three times. The organic phases were combined and dried over anhydrous Na2SO4. The resulting mixture was then concentrated under reduced pressure and washed with n-hexane, filtered, and oven dried to yield the product N2,N4-dibenzyl-6-(bis(4-methylphenyl)phosphine oxide-1,2,4-triazine-3,5(2H,4H)-dione 97.4 mg, 93% overall yield.

[0113]

[0114] The hydrogen nuclear magnetic resonance spectral data for the product obtained was 1 H NMR (400 MHz, CDC13) δ: 7.71 - 7.66 (m, 4H), 7.45 - 7.44 (m, 2H), 7.35 - 7.31 (m, 10H), 7.25 - 7.23 (m, 2H), 5.07 (s, 2H), 5.03 (s, 2H), 2.46 (s, 6H); 31 P NMR (162 MHz, CDC13) δ: 23.1 (s), consistent with the structure.

[0115] Example 19:

[0116]

[0117] Into a 15 mL reaction tube was added the substrate N2,N4-dibenzyl-1,2,4-triazine- 3,5(2H,4H)-dione (58.6 mg, 0.2 mmol, R 1 , R 2To a solution of N2,N4-dibenzyl-6-(bis(4-chlorophenyl)phosphine oxide)- 1,2,4-triazine-3,5(2H,4H)-dione (36.5 mg, 0.07 mmol) in 1 mL of DCM was added DBU (5.1 mg, 0.03 mmol) and 1 mL of DMC. The reaction was stirred at room temperature for 12 hours. The reaction was checked by TLC and was found to be complete. The DCM was evaporated and the residue was extracted with ethyl acetate and water three times. The organic phase was combined and dried over anhydrous Na2SO4. The mixture was then concentrated under reduced pressure and washed with n-hexane, filtered, and dried to give the product N2,N4-dibenzyl-6-(bis(4-chlorophenyl)phosphine oxide)- 1,2,4-triazine-3,5(2H,4H)-dione (36.5 mg, 100% yield).

[0118]

[0119] The hydrogen nuclear magnetic resonance spectrum data of the product obtained is 1 H NMR (400 MHz, CDC13) δ: 7.69-7.64 (m, 4H), 7.47-7.45 (m, 4H), 7.41-7.40 (m, 2H), 7.33-7.26 (m, 6H), 7.19-7.17 (m, 2H), 5.05 (s, 2H), 5.00 (s, 2H); 31 P NMR (162 MHz, CDC13) δ: 21.0 (s), consistent with the structure.

[0120] Example 20:

[0121]

[0122] To a solution of N2,N4-dibenzyl-1,2,4-triazine-3,5(2H,4H)-dione (58.6 mg, 0.2 mmol, the substituent R 1 , R 2 is benzyl) in 1 mL of DCM was added DBU (60.9 mg, 0.4 mmol) and 1 mL of DMC using a syringe. The reaction was stirred at room temperature for 12 hours. The reaction was checked by TLC and was found to be complete. The DMC was evaporated and the residue was extracted with ethyl acetate and water three times. The organic phase was combined and dried over anhydrous Na2SO4. The mixture was then concentrated under reduced pressure and washed with n-hexane, filtered, and dried to give the product N2,N4-dibenzyl-6-(bis(4-bromophenyl)phosphine oxide)- 1,2,4-triazine-3,5(2H,4H)-dione (35.2 mg, 28% yield).

[0123]

[0124] The hydrogen nuclear magnetic resonance spectrum data of the product obtained is 1 H NMR (400 MHz, CDCI3) δ: 7.61-7.55 (m, 8H), 7.41-7.39 (m, 2H), 7.32-7.26 (m, 6H), 7.18-7.17 (m, 2H), 5.04 (s, 2H), 5.00 (s, 2H); 31 P NMR (162 MHz, CDCI3) δ: 21.4 (s), consistent with the structural formula.

[0125] Example 21:

[0126]

[0127] Into a 15 ml reaction tube was added the substrate N2,N4-dibenzyl-1,2,4-triazine- 3,5(2H,4H)-dione (58.6 mg, 0.2 mmol, the substituent R 1 , R 2 is benzyl), ethyl phenylphosphonate (85 mg, 0.5 mmol) and a magnetic stirrer. DBU (60.9 mg, 0.4 mmol) and 1 ml of DMC were added by syringe. Stirring was carried out at room temperature in an open environment for 12 hours (at this time the reaction was open, air flowed through, and considered excess oxygen). TLC detection showed that the reaction was substantially complete. The DMC was evaporated by rotary evaporation, and the crude product was extracted with ethyl acetate and water three times. The organic phase was combined and dried with anhydrous Na2SO4. The resulting mixture was then concentrated under reduced pressure and washed with n-hexane, filtered, and dried to obtain the product N2,N4-dibenzyl-6-ethyl phenylphosphonate-1,2,4-triazine-3,5(2H,4H)-dione 45.6 mg, with a total yield of 49%.

[0128]

[0129] The hydrogen nuclear magnetic resonance spectrum data of the product obtained is 1 H NMR (400 MHz, CDCI3) δ: 7.94-7.88 (m, 2H), 7.63-7.58 (m, 1H), 7.52-7.47 (m, 2H), 7.46-7.43 (m, 2H), 7.31-7.27 (m, 6H), 7.24-7.22 (m, 2H), 5.14-5.11 (m, 1H), 5.01 (s, 2H), 4.99-4.96 (m, 1H), 4.38-4.23 (m, 2H), 1.38 (t, J = 8.0 Hz, 3H); 31 P NMR (162 MHz, CDCI3) δ: 22.9 (s), consistent with the structural formula.

[0130] Example 22 was carried out.

[0131]

[0132] A 15 mL reaction tube was charged with the substrate N4-benzyl-N2-(3-(2-methoxy-4-(3-oxobutyl)phenoxy)propyl)-1,2,4-triazine-3,5(2H,4H)-dione (43.7 mg, 0.1 mmol), diphenyl phosphine oxide (50.5 mg, 0.25 mmol) and a magnetic stir bar. DBU (30.5 mg, 0.2 mmol) and 0.5 mL of DMC were added via syringe. The reaction was stirred open to the air at room temperature for 12 hours (the reaction was open to the air and considered to be in excess oxygen). TLC indicated that the reaction was substantially complete. The DMC was evaporated and the crude product was extracted with ethyl acetate and water three times. The organic phases were combined and dried over anhydrous Na2SO4. The ethyl acetate was evaporated and the crude product was directly purified by column chromatography (ethyl acetate / petroleum ether = 4 / 1) to give the product N4-benzyl-6-(diphenylphosphoryl)-N2-(3-(2-methoxy-4-(3-oxobutyl)phenoxy)propyl)-1,2,4-triazine-3,5(2H,4H)-dione 34.4 mg, 54% overall yield.

[0133]

[0134] The hydrogen nuclear magnetic resonance spectrum data of the obtained product is 1 H NMR (400 MHz, CDCl3) δ: 7.62-7.57 (m, 4H), 7.41-7.37 (m, 2H), 7.29-7.24 (m, 4H), 7.12-7.09 (m, 3H), 7.05-7.03 (m, 2H), 6.52-6.46 (m, 3H), 4.87 (s, 2H), 3.90 (t, J = 6.0 Hz, 2H), 3.81 (t, J = 6.0 Hz, 2H), 3.50 (s, 3H), 2.68-2.64 (m, 2H), 2.58-2.54 (m, 2H), 1.97 (s, 3H), 1.95-1.92 (m, 2H); 31 P NMR (162 MHz, CDCl3) δ: 22.7 (s), consistent with the structure.

[0135] The details of the present application are known in the art.

Claims

1. A 6-phosphoryl-1,2,4-triazine-3,5(2 H , 4 H A method for preparing α-diketone derivatives, characterized by comprising the following steps: A 1,2,4-triazine-3,5(2 H , 4 H )-dione compound, a phosphoryl precursor, an oxidizing agent, and a base are added to a solvent and reacted at 0-75°C for 2-18 hours in an air atmosphere. After extraction, washing, filtration, or column chromatography, a 6-phosphoryl-substituted 1,2,4-triazine-3,5(2 H , 4 H )-dione derivative is obtained. wherein Molar ratio of 1,2,4-triazine-3,5(2 H , 4 H )-dione compound: phosphorus-based precursor: oxidizing agent: base = 1 : 1-4: 1-5: 0.01-5; The amount of solvent used is 1 to 15 ml per mmol of 1,2,4-triazine-3,5(2 H , 4 H )-dione compound. The structural formula of the 1,2,4-triazine-3,5(2 H , 4 H )-dione compound is: or ; wherein R 1 and R 2 are the same or different and are a hydrogen atom, a methyl group, an ethyl group, an allyl group, an acetylenyl group, an ethyl acetate group, a tert-butyl acetate group, an acetophenone group, a (2- (trimethylsilyl)ethoxy)methyl group, a furanose group, a deoxy furanose group, a (3-(2-methoxy-4-(3-oxobutyl)phenoxy)propyl) group, a phenyl group, a benzyl group, and a methyl, ethyl, fluorine atom, chlorine atom, bromine atom, trifluoromethyl group, cyano group, formyl ethyl ester group, nitro group, or methoxy-substituted aryl and benzyl group; The phosphoryl precursor is: , wherein R 3 and R 4 are the same or different and are phenyl, 4-methoxyphenyl, 4-methylphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, methoxy, ethoxy, isopropoxy; The oxidizing agent is di-trifluoroacetic acid iodobenzene, di-acetic acid iodobenzene, tert-butyl hydroperoxide, cumene hydroperoxide, tert-butyl peroxybenzoate, di-tert-butyl peroxide, diisopropylbenzene peroxide, peroxo benzoyl, peroxy acetic acid, m-chloro peroxy benzoic acid, hydrogen peroxide, potassium peroxodisulfate, sodium peroxodisulfate, ammonium peroxodisulfate, potassium peroxomonosulfate, oxygen or air; The base is cesium carbonate, potassium carbonate, sodium carbonate, lithium carbonate, cesium hydroxide, potassium hydroxide, sodium hydroxide, lithium hydroxide, cesium acetate, potassium acetate, sodium acetate, lithium acetate, potassium phosphate, dipotassium hydrogen phosphate, monopotassium phosphate, cesium hydrogen carbonate, potassium hydrogen carbonate, sodium hydrogen carbonate, lithium hydrogen carbonate, triethylamine, diethylamine, n-butylamine, pyridine, morpholine, pyrrolidine, piperidine, piperazine, 1,8-diazabicyclo[5.4.0]undec-7-ene or 1,4-diazabicyclo[2.2.2]octane.

2. The 6-phosphoryl-1,2,4-triazine-3,5(2) as described in claim 1 H , 4 H A method for preparing diketone derivatives, characterized in that the solvent is acetonitrile, propionitrile, dichloromethane, 1,2-dichloroethane, ethyl acetate, acetone, toluene, trifluorotoluene, methanol, ethanol, isopropanol, tetrahydrofuran, 1,4-dioxane, tetrahydropyran, 1,3-dioxane, diethyl ether, dibutyl ether, methyl tert-butyl ether, dimethyl carbonate, methyl cyclopentyl ether, 1,2-dimethoxyethane, N,N-dimethylformamide, or dimethyl sulfoxide.

3. The 6-phosphonoyl 1,2,4-triazine-3,5(2 H , 4 H )-dione derivative according to claim 1, wherein the 1,2,4-triazine-3,5(2 H , 4 H )-dione derivative is N2,N4-dibenzyl-1,2,4-triazine-3,5(2 H , 4 H )-dione, N2,N4-bis(4-fluorobenzyl)-1,2,4-triazine-3,5(2 H , 4 H )-dione, N2,N4-bis(4-chlorobenzyl)-1,2,4-triazine-3,5(2 H , 4 H )-dione, N2,N4-bis(4-cyanobenzyl)-1,2,4-triazine-3,5(2 H , 4 H )-dione, N2,N4-bis(4-methoxybenzyl)-1,2,4-triazine-3,5(2 H , 4 H )-dione, N2,N4-dimethyl-1,2,4-triazine-3,5(2 H , 4 H )-dione, N2,N4-bis(ethylacetate)-1,2,4-triazine-3,5(2 H , 4 H )-dione, N2,N4-bis(t-butylacetate)-1,2,4-triazine-3,5(2 H , 4 H )-dione, N2-phenyl-N4-methyl-1,2,4-triazine-3,5(2 H ,4 H )-dione, N2-(4-methylphenyl)-N4-methyl-1,2,4-triazine-3,5(2 H , 4 H )-dione, N2-(4-ethylphenyl)-N4-methyl-1,2,4-triazine-3,5(2 H , 4 H )-dione, N2-(4-fluorophenyl)-N4-methyl-1,2,4-triazine-3,5(2 H ,4 H )-dione, N2-(4-bromophenyl)-N4-methyl-1,2,4-triazine-3,5(2 H , 4 H )-dione, N2-(4-allyl)-N4-methyl-1,2,4-triazine-3,5(2 H , 4 H )-dione, N2-(4-allyl)-N4-methyl-1,2,4-triazine-3,5(2 H , 4 H )-dione, N2-(O 3´ ,O 5´ -bis-p-methylbenzoyl-2'-deoxyribosyl)-N4-methyl-1,2,4-triazine-3,5(2 H , 4 H )-dione or N4-benzyl-N2-(3-(2-methoxy-4-(3-oxobutyl)phenoxy)propyl)-1,2,4-triazine-3,5(2 H , 4 H )-dione.

4. The 6-phosphoryl-1,2,4-triazine-3,5(2) as described in claim 1 H , 4 H A method for preparing diketone derivatives, characterized in that the phosphoryl precursor is specifically diphenylphosphine oxide, bis(4-methoxyphenyl)phosphine oxide, bis(4-methylphenyl)phosphine oxide, bis(4-fluorophenyl)phosphine oxide, bis(4-chlorophenyl)phosphine oxide, bis(4-bromophenyl)phosphine oxide, methyl phenylphosphite, ethyl phenylphosphite, or isopropyl phenylphosphite.

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