Preparation method, intermediate and application of 1-alkylpyridine-2-ketone compound

Abstract

The invention relates to the field of organic synthesis, in particular to a preparation method of a 1-alkyl pyridine-2-ketone compound, an intermediate and application, the preparation method of the 1-alkyl pyridine-2-ketone compound comprises the following steps: (1) in an organic solvent, a compound III and an electrophilic alkylation reagent are subjected to a nitrogen alkylation reaction to prepare a compound II; and (2) carrying out hydrolysis reaction on the compound II in an aqueous solution of an alkaline reagent to prepare a compound I. According to the preparation method, a preparation method of firstly performing nitrogen alkylation and then performing hydrolysis is adopted, and a product with the purity being 95% or above is obtained with the total yield being 80% or above. # imgabs0 #

Description

Technical Field

[0001] The invention relates to the field of organic synthesis, and in particular to a preparation method, an intermediate and application of a 1-alkylpyridin-2-one compound. Background Art

[0002] The 2-pyridone structure is an amphiphilic nucleophile and an important pharmaceutical intermediate. For example, CN102584690A discloses that the 2-pyridone structure can be used as an intermediate for antitumor drugs and antiviral drugs.

[0003] WO2024138201A2 discloses a method for preparing 1-methyl-4-bromo-5-iodopyridin-2-one: using 4-bromo-5-iodopyridin-2-amine as a starting material, first introducing a carbonyl group at position 2 by Sandmeyer reaction, and then introducing a methyl group at position 1. The total yield of the two steps is 62%, which is relatively low.

[0004]

[0005] WO2022167682A1 also discloses a method for preparing 1-methyl-3-chloro-6-bromopyridin-2-one: using 2,3-dichloro-6-bromopyridine as the starting material, a carbonyl group is first introduced at the 2 position by hydrolysis, and then a methyl group is introduced at the 1 position. The total yield of the two steps is 29%, which is not high. In addition, the first step of hydrolysis needs to react at 100°C for 12 hours. Not only is the reaction temperature high, but the reaction time is also long.

[0006]

[0007] Therefore, a method for preparing 1-alkylpyridin-2-one compounds with high yield has become a technical problem that researchers are eager to solve. Summary of the invention

[0008] The present invention is made to solve the above problems, and aims to provide a preparation method of 1-alkylpyridin-2-one compounds with mild conditions, wide application range and higher yield, corresponding intermediates and applications.

[0009] The present invention provides a method for preparing a 1-alkylpyridin-2-one compound, which comprises the following steps:

[0010] (1) Compound III undergoes nitrogen alkylation reaction with an electrophilic alkylating agent in an organic solvent to obtain compound II;

[0011] (2) Compound II undergoes a hydrolysis reaction in an aqueous solution of an alkaline reagent to obtain Compound I;

[0012]

[0013] Among them, R 1 C 1-6 alkyl,

[0014] X is a halogen,

[0015] R 3 , R 4 and R 5 are independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C substituted by one or more halogens 1-6 Alkyl or C substituted by one or more halogens 1-6 Alkoxy; the plurality is 2, 3, 4, 5 or 6;

[0016] R 6 For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C substituted by one or more halogens 1-6 Alkyl or C substituted by one or more halogens 1-6 Alkoxy; the plurality is 2, 3, 4, 5 or 6;

[0017] Y - It is an anion.

[0018] In one embodiment, the Y - Can be F - , Cl - Br - ,I - , BF 4- , ClO 4- 、CH3SO 3- or CF3SO3 - ; preferably 1 - or BF4 - .

[0019] In one embodiment, X can be fluorine, chlorine, bromine or iodine.

[0020] In one embodiment, the electrophilic alkylating agent may be one or more of a monohalogenated alkane, a trialkyloxonium tetrafluoroborate, a dialkyl sulfate, and methyl trifluoromethylsulfonate; the monohalogenated alkane is preferably a brominated alkane or an iodinated alkane; the trialkyloxonium tetrafluoroborate is preferably a trimethyloxonium tetrafluoroborate or a triethyloxonium tetrafluoroborate; the dialkyl sulfate is preferably a dimethyl sulfate or a diethyl sulfate.

[0021] In one embodiment, when R 1 When R is methyl, the electrophilic alkylating agent may be methyl iodide, dimethyl sulfate, trimethyloxonium tetrafluoroborate or methyl trifluoromethanesulfonate; when R1 When the group is ethyl, the electrophilic alkylating agent may be ethyl iodide, diethyl sulfate or triethyloxonium tetrafluoroborate.

[0022] In one embodiment, the molar ratio of the electrophilic alkylating agent to compound III may be (1.0-4.0):1, such as 1.0:1, 1.3:1 or 2.0:1.

[0023] In one embodiment, the organic solvent may be one or more of dichloromethane, tetrahydrofuran, diethyl ether, acetonitrile, ethyl acetate and ethanol, preferably dichloromethane.

[0024] In one embodiment, the volume mass ratio of the organic solvent to compound III may be (2-20) mL:1 g, preferably 6 mL:1 g, 8 mL:1 g or 10 mL:1 g.

[0025] In one embodiment, the reaction temperature of the nitrogen alkylation reaction can be 0-50°C, preferably 0-30°C.

[0026] In one embodiment, the reaction time of the nitrogen alkylation reaction can be 2-30 hours.

[0027] In one embodiment, after the nitrogen alkylation reaction is completed, compound II can be obtained by simple post-treatment, and the obtained compound II can be directly used in the next reaction without purification.

[0028] In one embodiment, the alkaline agent may be any one or more of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate and potassium bicarbonate, preferably sodium bicarbonate.

[0029] In one embodiment, the amount of the alkaline agent used is determined by the pH value of the reaction solution after the reaction between Compound II and the aqueous solution of the alkaline agent, and the pH value can be 7-9, preferably 8.

[0030] In one embodiment, the reaction temperature of the hydrolysis reaction may be 40-60°C, preferably 45-55°C.

[0031] In one embodiment, the reaction time of the hydrolysis reaction may be 20-40 min.

[0032] In one embodiment, after the hydrolysis reaction is completed, the solid is directly filtered and dried to obtain compound I.

[0033] In one embodiment, R 1 , R 3 , R 4 , R 5 and R 6 In the C 1-6 The alkyl group may be C 1-4Alkyl, for example methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl.

[0034] In one embodiment, R 3 , R 4 , R 5 and R 6 In the C 1-6 The alkoxy group may be C 1-4 Alkoxy, for example methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy or tert-butoxy.

[0035] In one embodiment, R 1 C 1-4 alkyl.

[0036] In one embodiment, R 3 , R 4 and R 5 are independently halogen, C 1-4 Alkyl, C 1-4 Alkoxy, C substituted by one or more halogens 1-4 Alkyl or C substituted by one or more halogens 1-4 Alkoxy; the plurality is 2, 3, 4, 5 or 6.

[0037] In one embodiment, R 6 For halogen, C 1-4 Alkyl, C 1-4 Alkoxy, C substituted by one or more halogens 1-4 Alkyl or C substituted by one or more halogens 1-4 Alkoxy; the plurality is 2, 3, 4, 5 or 6.

[0038] In one embodiment, 1-methyl-4-bromo-5-iodopyridin-2-one is prepared by the following preparation method, the steps of which are as follows:

[0039]

[0040] (1) Compound III-1 undergoes a nitrogen alkylation reaction with trimethyloxonium tetrafluoroborate in an organic solvent to obtain compound II-1;

[0041] (2) Compound II-1 undergoes a hydrolysis reaction with an aqueous solution of an alkaline reagent to obtain compound I-1.

[0042] In one embodiment, the preparation method of 1-methyl-4-bromo-5-iodopyridin-2-one comprises the following steps:

[0043]

[0044] (1) Compound III-1 is reacted with trimethyloxonium tetrafluoroborate in dichloromethane at room temperature, and after the reaction is completed, the mixture is concentrated to obtain compound II-1;

[0045] (2) Compound II-1 is hydrolyzed in an aqueous solution of sodium bicarbonate at 50±5°C, filtered, and the solid is dried to obtain Compound I-1.

[0046] The present invention also provides a compound II Among them, the Y - F - , Cl - Br - ,I - , ClO 4- 、CH3SO 3- CF3SO 3- or BF 4- .

[0047] In one embodiment, compound II is

[0048] The present invention also provides an application of a 1-alkylpyridin-2-one compound, wherein the application is a method for preparing 1-methyl-4-bromo-5-phenylpyridin-2-one using compound I-1 as a raw material, the method comprising the following steps: in the presence of a solvent, sodium carbonate and Pd(PPh3)4, 1-methyl-4-bromo-5-iodopyridin-2-one and phenylboronic acid undergo a coupling reaction to prepare 1-methyl-4-bromo-5-phenylpyridin-2-one;

[0049]

[0050] The solvent is a mixed solvent of toluene and water.

[0051] In the application, the mass ratio of the Pd(PPh3)4 and the compound I-1 can be (0.001-0.2):1, preferably (0.01-0.2):1.

[0052] In the application, the molar ratio of the sodium carbonate to the compound I-1 may be (1.0-5.0):1, preferably (2.0-3.0):1.

[0053] In the application, the molar ratio of the phenylboric acid to the compound I-1 may be (1.0-2.0):1, preferably (1.2-1.5):1, for example 1.25:1 or 1.4:1.

[0054] In the application, the volume mass ratio of the solvent to the compound I-1 may be (2.0-20.0) mL:1 g, preferably (5.0-15.0) mL:1 g, for example 10.0 mL:1 g.

[0055] In the application, the volume ratio of toluene to water may be (0.5-3.0):1, preferably 1.5:1.

[0056] In the application, the reaction temperature may be 70-110°C, preferably 80-85°C.

[0057] In the application, the reaction time may be 4-30 h, preferably 5-24 h.

[0058] In the application, compound I-1 and phenylboronic acid are reacted at 80-85°C in a mixed solvent of toluene and water in the presence of sodium carbonate and Pd(PPh3)4. After the reaction is completed, the temperature is cooled to room temperature, the liquids are separated, the organic phase is taken, dried, and column chromatography is performed to obtain compound IV-1.

[0059] In the application, the preparation method of 1-methyl-4-bromo-5-phenylpyridin-2-one comprises the following steps:

[0060]

[0061] (1) The compound II-1 undergoes a hydrolysis reaction with an aqueous solution of an alkaline reagent to obtain a compound I-1;

[0062] (2) In the presence of a solvent, sodium carbonate and Pd(PPh3)4, 1-methyl-4-bromo-5-iodopyridin-2-one and phenylboronic acid undergo a coupling reaction to prepare 1-methyl-4-bromo-5-phenylpyridin-2-one;

[0063] The solvent is a mixed solvent of toluene and water.

[0064] In the application, the reaction conditions of the preparation method of the compound I-1 are the same as those described in the preparation method of the 1-alkylpyridin-2-one compound.

[0065] In the application, the reaction conditions of the preparation method of the compound IV-1 are the same as those described in the application of the 1-alkylpyridin-2-one compound.

[0066] In the application, the preparation method of 1-methyl-4-bromo-5-phenylpyridin-2-one comprises the following steps:

[0067]

[0068] (1) Compound III-1 undergoes nitrogen alkylation reaction with an electrophilic alkylating agent in an organic solvent to obtain compound II-1;

[0069] (2) hydrolyzing compound II-1 with an aqueous solution of an alkaline reagent to obtain compound I-1;

[0070] (3) In the presence of a solvent, sodium carbonate and Pd(PPh3)4, 1-methyl-4-bromo-5-iodopyridin-2-one and phenylboronic acid undergo a coupling reaction to prepare 1-methyl-4-bromo-5-phenylpyridin-2-one;

[0071] The solvent is a mixed solvent of toluene and water.

[0072] In the application, the reaction conditions of the preparation method of the compound I-1 are the same as those described in the preparation method of the 1-alkylpyridin-2-one compound.

[0073] In the application, the reaction conditions of the preparation method of the compound IV-1 are the same as those described in the application of the 1-alkylpyridin-2-one compound.

[0074] Functions and Effects of the Invention

[0075] The preparation method of 1-methylpyridine-2-one compounds involved in the present invention adopts a preparation method of first nitrogen alkylation and then hydrolysis, so as to obtain a product with a purity of more than 95% at a total yield of more than 80%.

[0076] The present invention relates to an application of 1-alkylpyridin-2-one compounds, which is a preparation method for preparing 1-methyl-4-bromo-5-phenylpyridin-2-one using compound I-1 as a raw material. Since the preparation method uses toluene and water as solvents, unexpectedly, an 80% yield can be achieved when only 1wt% of palladium catalyst is used, which is much higher than the existing level. BRIEF DESCRIPTION OF THE DRAWINGS

[0077] Figure 1 is the HPLC spectrum of II-1 in Example 1 of the present invention;

[0078] Figure 2 is the H NMR spectrum of II-1 in Example 1 of the present invention;

[0079] Figure 3 is an HPLC spectrum of 1-methyl-4-bromo-5-iodopyridin-2-one with a purity of 95.8% in Example 1 of the present invention;

[0080] Figure 4 This is the HPLC spectrum of 1-methyl-4-bromo-5-iodopyridin-2-one in Example 1 of the present invention with a purity of 98.2%. DETAILED DESCRIPTION

[0081] In order to make the technical means, creative features, objectives and effects achieved by the present invention easier to understand, the present invention is described in detail below in conjunction with embodiments and drawings.

[0082] Example 1

[0083]

[0084] Under nitrogen protection, 400 mL of dichloromethane, 50 g of 2-chloro-4-bromo-5-iodopyridine (0.157 mol, 1.0 eq) and 30.2 g of trimethoxylium tetrafluoroboric acid (0.204 mol, 1.3 eq) were placed in a three-necked flask and stirred at room temperature for 3 h. After the reaction solution was concentrated, 66.0 g of crude compound II-1 was obtained with a purity of 95.4% (HPLC spectrum as shown in Figure 1 As shown, RT = 3.716min; NMR spectrum as shown Figure 2 The solvent was CD3CN), and it was directly used in the next reaction without further purification.

[0085] 66.0 g of the crude compound II-1 obtained in the previous step was added to 50 mL of water with stirring, and a saturated sodium bicarbonate aqueous solution was added dropwise until the system pH was 8, and the mixture was heated to 50±5°C for 30 min. The solid was filtered while hot and dried to obtain 49.1 g of the crude compound I-1 with a purity of 95.8% (HPLC spectrum as shown in FIG. Figure 3 Column treatment gave 44.8 g of 1-methyl-4-bromo-5-iodopyridin-2-one with a purity of 98.2% (HPLC spectrum as shown in Figure 4 As shown, RT = 6.132 min), the two-step reaction yield was 90.8%.

[0086] Example 2

[0087]

[0088] Under nitrogen protection, 300 mL of dichloromethane and 50 g of 2-chloro-6-methylpyridine (0.39 mol, 1.0 eq) were placed in a three-necked flask. Under an ice bath, 110.7 g of iodomethane (0.78 mol, 2.0 eq) was added dropwise. A precipitate was precipitated. After 1 hour, the precipitate was filtered and the filter cake was taken to obtain 92.1 g of the crude product of compound II-2, which was directly used in the next reaction without further purification.

[0089] 92.1 g of crude compound II-2 obtained in the previous step was added to 120 mL of water and stirred, saturated sodium bicarbonate solution was added dropwise until the pH of the system was 8, heated to 50±5°C for 30 min, filtered while hot, and the solid was filtered and dried to obtain 42.3 g of crude compound I-2 with a purity of 93.8%. After column treatment, 38.5 g of 1,6-dimethylpyridin-2-one was obtained with a purity of 99.0% and a two-step reaction yield of 80.2%.

[0090] Example 3

[0091]

[0092] Under nitrogen protection, 0.5 mL of dichloromethane and 50 mg of 2-bromo-4-methylpyridine (0.29 mmol, 1.0 eq) were placed in a three-necked flask, and 47.7 mg of methyl trifluoromethanesulfonate (0.29 mmol, 1.0 eq) was added dropwise at -78°C. After the addition was completed, the temperature was raised to room temperature and the reaction was carried out for 20 hours. Methyl tert-butyl ether was added to the reaction flask, filtered, and the filter cake was taken to obtain 80.9 mg of a crude product of compound II-3, which was directly used in the next step without further purification.

[0093] 80.9 g of crude compound II-3 obtained in the previous step was added to 100 mL of water and stirred, saturated sodium bicarbonate aqueous solution was added dropwise until the pH of the system was 8, heated to 50±5°C for 30 min, filtered while hot, and the solid was filtered out and dried to obtain 30.8 mg of crude compound I-3 with a purity of 94.8%. After column treatment, 28.7 mg of 1,4-dimethylpyridin-2-one was obtained with a purity of 99.5%. The yield of the two-step reaction was 80.4%.

[0094] Example 4

[0095]

[0096] Under nitrogen protection, 100 mL of dichloromethane, 10 g of 2-chloro-4-bromo-5-iodopyridine (0.031 mol, 1.0 eq) and 6.04 g of trimethoxonium tetrafluoroboric acid (0.041 mol, 1.3 eq) were placed in a three-necked flask and stirred at room temperature for 3 h. After the reaction solution was concentrated, 12.9 g of a crude product of compound II-1 was obtained, which was directly used in the next step without further purification.

[0097] 12.9 g of the crude compound II-1 obtained in the previous step was added to 20 mL of water with stirring, and 10 wt% aqueous sodium hydroxide solution was added dropwise until the pH of the system reached 8. The mixture was heated to 50±5°C and reacted for 30 min. The solid was filtered while hot and dried to obtain 8.64 g of the crude compound I-1. The solid was filtered and dried to obtain 8.21 g of 1-methyl-4-bromo-5-iodopyridin-2-one with a purity of 98.9% and a two-step reaction yield of 84.4%.

[0098] Example 5

[0099]

[0100] 50 g (0.159 mol, 1.0 eq) of compound I-1, 24.26 g of phenylboric acid (0.199 mol, 1.25 eq), 500 mg of Pd(PPh3)4 (0.433 mmol, 1 wt%), 33.70 g of sodium carbonate (0.318 mol, 2.0 eq), 300 mL of toluene and 200 mL of water were added to a reaction vessel, replaced with nitrogen three times, heated to 80-85°C and stirred for reaction, reacted for 24 hours, cooled to room temperature, separated and processed, the organic phase was concentrated, dried and column-filtered to obtain 33.6 g of solid with a purity of 98.8% and a reaction yield of 80.0%.

[0101] Comparative Example 1

[0102]

[0103] 1.0g (3.2mmol, 1.0eq) of compound I-1, 549mg of phenylboric acid (4.5mmol, 1.4eq), 185mg of Pd(PPh3)4 (0.16mmol, 18.5wt%), 678mg of sodium carbonate (6.4mmol, 2.0eq), 6mL of N,N-dimethylformamide, 4mL of water were stirred, nitrogen was replaced three times, the temperature was raised to 80-85℃ to react, the temperature was lowered to room temperature after reacting for 24h, concentrated, washed with water, dried, and passed through a column to obtain 0.470g of solid with a yield of 55.6%.

[0104] The preparation method of 1-methylpyridine-2-one compounds involved in the above embodiment adopts a preparation method of methylation followed by hydrolysis, so as to obtain a product with a purity of more than 95% at a total yield of more than 80%.

[0105] Furthermore, the applicant unexpectedly discovered that the hydrolysis reaction provided by the above embodiment has unexpectedly good selectivity. Even if the pyridine ring is substituted with multiple halogens, only the halogen atoms substituted on the carbon adjacent to the nitrogen atom undergo hydrolysis reaction, while the halogen atoms at other positions are not affected.

[0106] Furthermore, the experimental process is easy to operate and the reaction conditions are mild. Only simple post-treatment is required to directly obtain a product with a purity of more than 95%, which is suitable for large-scale industrial production.

[0107] The above embodiment involves an application of a 1-alkylpyridin-2-one compound, which is a preparation method for preparing 1-methyl-4-bromo-5-phenylpyridin-2-one using compound I-1 as a raw material. Since the preparation method uses toluene and water as solvents, unexpectedly, an 80% yield can be achieved using only 1wt% of palladium catalyst, which is much higher than the existing level.

[0108] The above-mentioned embodiments are preferred examples of the present invention and are not intended to limit the protection scope of the present invention.

Claims

1. A method for preparing a 1-alkylpyridin-2-one compound, characterized in that: It includes the following steps: (1) Compound III undergoes nitrogen alkylation reaction with an electrophilic alkylating agent in an organic solvent to obtain compound II; (2) Compound II undergoes a hydrolysis reaction in an aqueous solution of an alkaline reagent to obtain Compound I; Among them, R 1 C 1-6 alkyl, X is a halogen, R 3 , R 4 and R 5 are independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C substituted by one or more halogens 1-6 Alkyl or C substituted by one or more halogens 1-6 Alkoxy; the plurality is 2, 3, 4, 5 or 6; R 6 For hydrogen, C 1-6 Alkyl, C 1-6 Alkoxy, C substituted by one or more halogens 1-6 Alkyl or C substituted by one or more halogens 1-6 Alkoxy; the plurality is 2, 3, 4, 5 or 6; Y - It is an anion.

2. The method for preparing 1-alkylpyridin-2-one compounds according to claim 1, characterized in that: The Y - F - , Cl - Br - ,I - , BF 4- , ClO 4- 、CH3SO 3- or CF3SO 3- ; And / or, X is fluorine, chlorine, bromine or iodine.

3. The method for preparing 1-alkylpyridin-2-one compounds according to claim 1, characterized in that: The preparation method meets one or more of the following conditions: ① The electrophilic alkylating agent is one or more of a haloalkane, a trialkyloxonium tetrafluoroborate, a dialkyl sulfate and methyl trifluoromethanesulfonate; ② The molar ratio of the electrophilic alkylating agent to compound III is (1.0-4.0):1; ③ The organic solvent is one or more of dichloromethane, tetrahydrofuran, ether, acetonitrile, ethyl acetate and ethanol; ④ The volume mass ratio of the organic solvent to compound III is (2-20) mL:1 g; ⑤ The reaction temperature of the nitrogen alkylation reaction is 0-50°C; ⑥ The reaction time of the nitrogen alkylation reaction is 2-30h; ⑦ The alkaline reagent is any one or more of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate and potassium bicarbonate; ⑧ The reaction temperature of the hydrolysis reaction is 40-60°C; ⑨The reaction time of the hydrolysis reaction is 20-40min.

4. The method for preparing 1-alkylpyridin-2-one compounds according to claim 3, characterized in that: The preparation method meets one or more of the following conditions: ① The monohaloalkane is a bromide or an iodide; ② The trialkyloxonium tetrafluoroborate is trimethyloxonium tetrafluoroborate or triethyloxonium tetrafluoroborate; ③ The dialkyl sulfate is dimethyl sulfate or diethyl sulfate; ④ The molar ratio of the electrophilic alkylating agent to compound III is 1.0:1, 1.3:1 or 2.0:1; ⑤ The organic solvent is dichloromethane; ⑥ The volume mass ratio of the organic solvent to compound III is 6 mL: 1 g, 8 mL: 1 g or 10 mL: 1 g; 7. The alkaline reagent is sodium bicarbonate; ⑧The reaction temperature of the hydrolysis reaction is 45-55°C.

5. The method for preparing 1-alkylpyridin-2-one compounds according to claim 1, characterized in that: R 1 , R 3 , R 4 , R 5 and R 6 In the C 1-6 Alkyl is C 1-4 Alkyl; and / or, R 3 , R 4 , R 5 and R 6 In the C 1-6 Alkoxy is C 1-4 Alkoxy.

6. The method for preparing 1-alkylpyridin-2-one compounds according to claim 1, characterized in that: R 1 C 1-4 alkyl; and / or, R 3 , R 4 and R 5 are independently hydrogen, halogen, C 1-4 Alkyl, C 1-4 Alkoxy, C substituted by one or more halogens 1-4 Alkyl or C substituted by one or more halogens 1-4 Alkoxy; the plurality is 2, 3, 4, 5 or 6; and / or, R 6 For hydrogen, C 1-4 Alkyl, C 1-4 Alkoxy, C substituted by one or more halogens 1-4 Alkyl or C substituted by one or more halogens 1-4 Alkoxy; the plurality is 2, 3, 4, 5 or 6.

7. The method for preparing a 1-alkylpyridin-2-one compound according to any one of claims 1 to 6, characterized in that: The preparation method of 1-methyl-4-bromo-5-iodopyridin-2-one comprises the following steps: (1) Compound III-1 undergoes a nitrogen alkylation reaction with trimethyloxonium tetrafluoroborate in an organic solvent to obtain compound II-1; (2) Compound II-1 undergoes hydrolysis reaction in an aqueous solution of an alkaline reagent to obtain compound I-1.

8. An application of a 1-alkylpyridin-2-one compound, characterized in that: The application is a preparation method for preparing 1-methyl-4-bromo-5-phenylpyridin-2-one using compound I-1 as a raw material, which comprises the following steps: In the presence of a solvent, sodium carbonate and Pd(PPh3)4, 1-methyl-4-bromo-5-iodopyridin-2-one and phenylboronic acid undergo a coupling reaction to prepare 1-methyl-4-bromo-5-phenylpyridin-2-one; The solvent is a mixed solvent of toluene and water.

9. The use of 1-alkylpyridin-2-one compounds as claimed in claim 8, characterized in that: The preparation method of 1-methyl-4-bromo-5-phenylpyridin-2-one satisfies one or more of the following conditions: ① The mass ratio of the Pd(PPh3)4 and the compound I-1 is (0.001-0.2):1; ② The molar ratio of the sodium carbonate to the compound I-1 is (1.0-5.0):1; ③ The molar ratio of the phenylboric acid to the compound I-1 is (1.0-2.0):1; ④ The volume mass ratio of the solvent to the compound I-1 is (2.0-20.0) mL:1 g; ⑤ The volume ratio of toluene and water is (0.5-3.0):1; ⑥ The reaction temperature is 70-110°C; ⑦ The reaction time is 4-30h; ⑧ The preparation method of the compound I-1 is as described in the preparation method of the 1-alkylpyridin-2-one compound according to any one of claims 1 to 7.

10. A compound II It is characterized in that The Y - F - , Cl - Br - ,I - , ClO 4- 、CH3SO 3- CF3SO 3- or BF 4- .

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