2-methoxy-4-amino-6-methylpyridine and synthesis method thereof

Abstract

The present application discloses a 2-methoxy-4-amino-6-methylpyridine and a synthesis method thereof, which comprises the steps of: adding 2-chloro-6-methylpyridine-4-carboxylic acid to an organic solvent I, and then adding methoxide to react the 2-chloro-6-methylpyridine-4-carboxylic acid to 2-methoxy-6-methylpyridine-4-carboxylic acid; adding the 2-methoxy-6-methylpyridine-4-carboxylic acid obtained in step S1001 to an organic solvent II, then adding triethylamine and di-tert-butyl dicarbonate, and then dropping diphenylphosphoryl azide to react to obtain (2-methoxy-6-methylpyridine-4-yl) tert-butyl carbamate; adding the (2-methoxy-6-methylpyridine-4-yl) tert-butyl carbamate obtained in step S1002 to an organic solvent III, and adding a hydrogen chloride organic solution to react to obtain 2-methoxy-4-amino-6-methylpyridine.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, in particular to 2-methoxy-4-amino-6-methylpyridine and a synthesis method thereof. Background Art

[0002] Pyridine compounds are an important class of heterocyclic compounds with strong anti-cancer, antiviral, cardiotonic, and antihypertensive physiological activities. They are widely used in the research and development of new drugs in the fields of medicine, veterinary drugs, and pesticides.

[0003] The compound 2-methoxy-4-amino-6-methylpyridine is an important pyridine compound and also an important molecular building block. 2-methoxy-4-amino-6-methylpyridine is a key intermediate; for example, in patent US2018 / 265517, it is used to synthesize compounds that can inhibit EZH2 activity; for example, in patent WO2024 / 160722, it is used to synthesize tricyclic azone derivatives as XC system inhibitors.

[0004] The conventional synthesis route of the prior art compound 2-methoxy-4-amino-6-methylpyridine is to use 2,4-dichloro-6-methylpyridine as a raw material. In the first step, 2,4-dichloro-6-methylpyridine is converted into 2-chloro-6-methyl-pyridine-4-amine, and in the second step, it is converted into 2-methoxy-4-amino-6-methylpyridine, and the preparation is prepared by two steps of reaction.

[0005] However, in the first step of the reaction, since the chlorine at the 2- and 4-positions of 2,4-dichloro-6-methylpyridine are easily removed by the amine group, it is difficult to control the reaction selectivity, resulting in purification difficulties and low yields. Summary of the invention

[0006] Based on the above background, the present application provides a method for synthesizing 2-methoxy-4-amino-6-methylpyridine, which comprises the steps of: S1001, adding 2-chloro-6-methylpyridine-4-carboxylic acid to an organic solvent I, and then adding methoxide to react 2-chloro-6-methylpyridine-4-carboxylic acid to form 2-methoxy-6-methylpyridine-4-carboxylic acid; S1002, adding the 2-methoxy-6-methylpyridine-4-carboxylic acid prepared in step S1001 to the organic solvent II, then adding triethylamine and di-tert-butyl dicarbonate, and then adding diphenylphosphoryl azide dropwise to react to obtain (2-methoxy-6-methylpyridin-4-yl)carbamic acid tert-butyl ester; S1003, adding tert-butyl (2-methoxy-6-methylpyridin-4-yl)carbamate obtained in step S1002 to organic solvent III, and adding hydrogen chloride organic solution to react to obtain 2-methoxy-4-amino-6-methylpyridine.

[0007] Preferably, in step S1001, during the reaction, at least one of the following conditions is satisfied: The methoxide is sodium methoxide; The reaction temperature is 80-200°C; The reaction time is 2-6 hours; The mass volume ratio of the 2-chloro-6-methylpyridine-4-carboxylic acid to the organic solvent I is 1:(5-40) g / mL; The molar ratio of 2-chloro-6-methylpyridine-4-carboxylic acid to methoxide is 1:(2.00-5.00); The organic solvent I is selected from one or more of dimethyl sulfoxide, dimethylformamide or dimethylacetamide.

[0008] Preferably, after the reaction in step S1001 is completed and before step S1002 is performed, a first post-treatment is performed to obtain the 2-methoxy-6-methylpyridine-4-carboxylic acid, wherein the first post-treatment step comprises: S1101, cooling the reaction solution and adding ice water; S1102, adjust the pH of the reaction solution to 3-4 with an acidic aqueous solution, extract with an organic solvent IV, combine the organic phases, wash, dry, filter, and add petroleum ether for pulping to obtain 2-methoxy-6-methylpyridine-4-carboxylic acid.

[0009] Preferably, in step S1102, the acidic aqueous solution is selected from one or more of hydrochloric acid solution, sulfuric acid solution, nitric acid solution, and acetic acid solution; the organic solvent IV is selected from one or more of ethyl acetate, butyl acetate, chloroform, toluene, dichloromethane, and dichloroethane.

[0010] Preferably, in step S1002, at least one of the following conditions is met: The molar ratio of the 2-methoxy-6-methylpyridine-4-carboxylic acid to triethylamine is 1:(1.00-3.00); The molar ratio of the 2-methoxy-6-methylpyridine-4-carboxylic acid to di-tert-butyl dicarbonate is 1:(1.00-5.00); The molar ratio of 2-methoxy-6-methylpyridine-4-carboxylic acid to diphenylphosphoryl azide is 1:(1.00-3.00); The mass volume ratio of the 2-methoxy-6-methylpyridine-4-carboxylic acid to the organic solvent II is 1:(5-40) g / mL; The reaction time is 10-200 hours; The reaction temperature is 70-200°C; The organic solvent II is selected from one or more of tert-butyl alcohol, ethanol or isopropanol.

[0011] Preferably, after the reaction in step S1002 is completed and before step S1003 is performed, a second post-treatment is performed to obtain tert-butyl (2-methoxy-6-methylpyridin-4-yl)carbamate; the second post-treatment comprises the steps of: S2101, after the reaction is completed, most of the solvent is concentrated under reduced pressure, and then water is added; S2102, extract with organic solvent V, combine the organic phases, wash, dry, filter, and spin dry to obtain tert-butyl (2-methoxy-6-methylpyridin-4-yl)carbamate; In step S2102, the organic solvent V is selected from one or more of ethyl acetate, butyl acetate, chloroform, toluene, dichloromethane, and dichloroethane.

[0012] Preferably, in the step S1003, after adding the hydrogen chloride organic solution for reaction, the 2-methoxy-4-amino-6-methylpyridine is obtained by a third post-treatment, and the third post-treatment comprises the steps of: S3101, after the reaction is complete, filtering the reaction solution to obtain a solid; S3102, the solid is stirred with a mixed organic solvent of petroleum ether and ethyl acetate in a volume ratio of 10:1 for 20-50 minutes, then filtered, the solid is dissolved with water, the pH is adjusted to 8-9 with an alkaline aqueous solution, extracted with an organic solvent VII, the organic phases are combined, the organic phases are washed, dried, filtered, and spin-dried, and petroleum ether is added to pulp to obtain 2-methoxy-4-amino-6-methylpyridine.

[0013] Preferably, in step S3102, the alkaline aqueous solution is selected from one or more of a sodium bicarbonate solution, a sodium carbonate solution, a potassium carbonate solution, a sodium hydroxide solution, and a potassium hydroxide solution; In step S3102, the organic solvent VII is selected from one or more of ethyl acetate, butyl acetate, chloroform, toluene, dichloromethane, and dichloroethane.

[0014] Preferably, in step S1003, at least one of the following conditions is met: The hydrogen chloride organic solution is selected from one or more of hydrogen chloride ethyl acetate solution, hydrogen chloride 1,4-dioxane solution, and hydrogen chloride methanol solution; The organic solvent III is selected from one or more of ethyl acetate, 1,4-dioxane or methanol; The mass volume ratio of the (2-methoxy-6-methylpyridin-4-yl)carbamic acid tert-butyl ester to the organic solvent III is 1:(5-40) g / mL.

[0015] According to another aspect, the present application provides a 2-methoxy-4-amino-6-methylpyridine, which is prepared based on any of the above-described methods for synthesizing 2-methoxy-4-amino-6-methylpyridine.

[0016] Compared with the prior art, the present invention has the following beneficial effects: The present invention provides a preparation method of 2-methoxy-4-amino-6-methylpyridine, which uses the compound 2-chloro-6-methylpyridine-4-carboxylic acid as a raw material, first converts it into the compound 2-methoxy-6-methylpyridine-4-carboxylic acid, then converts it into the compound (2-methoxy-6-methylpyridin-4-yl)carbamic acid tert-butyl ester, and finally converts it into the target compound 2-methoxy-4-amino-6-methylpyridine through a deprotection reaction. In the key step of the synthesis method, the auxiliary material Boc anhydride is creatively added, and diphenyl phosphoryl azide is added dropwise after the system is refluxed, so that the raw materials of this step of the reaction are completely converted, and no by-products are generated, and the intermediate compound 3-iodo-1H-indole-2-carboxylic acid ethyl ester is obtained with a high yield; finally, a synthesis route of 2-methoxy-4-amino-6-methylpyridine with simple operation, low cost, mild reaction conditions, simple post-treatment and ideal yield is obtained. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 The schematic diagram is a route diagram of the synthesis method of 2-methoxy-4-amino-6-methylpyridine.

[0018] Figure 2 This is the H NMR spectrum of compound 4 (2-methoxy-4-amino-6-methylpyridine) in Example 1. DETAILED DESCRIPTION

[0019] The following description is used to disclose the present invention so that those skilled in the art can implement the present invention. The preferred embodiments described below are only examples, and those skilled in the art can think of other obvious variations. The basic principles of the present invention defined in the following description can be applied to other embodiments, variations, improvements, equivalents, and other technical solutions that do not deviate from the spirit and scope of the present invention.

[0020] As an important intermediate building block, the synthesis of 2-methoxy-4-amino-6-methylpyridine is very common. In the prior art, the conventional synthesis route is to use 2,4-dichloro-6-methylpyridine as the raw material. The first step is to convert 2,4-dichloro-6-methylpyridine into 2-chloro-6-methyl-pyridine-4-amine, and the second step is to convert it into 2-methoxy-4-amino-6-methylpyridine, and then prepare it through two steps of reaction. However, in the first step of the reaction, it is difficult to control the reaction selectivity, resulting in difficulty in purification and low yield.

[0021] To this end, the present application has invented a new synthetic route for 2-methoxy-4-amino-6-methylpyridine. When 2-methoxy-4-amino-6-methylpyridine is synthesized by the route of the present application, the reaction conditions required by the synthetic route are relatively mild, the potential safety hazard is low, and the purification is easy with a high yield.

[0022] refer to Figure 1 Specifically, in one embodiment, the synthesis method of 2-methoxy-4-amino-6-methylpyridine comprises: S1001, adding 2-chloro-6-methylpyridine-4-carboxylic acid (compound 1) to an organic solvent I, and then adding methoxide, such as sodium methoxide, to react 2-chloro-6-methylpyridine-4-carboxylic acid to 2-methoxy-6-methylpyridine-4-carboxylic acid (compound 2); S1002, adding 2-methoxy-6-methylpyridine-4-carboxylic acid prepared in step S1001 to organic solvent II, then adding triethylamine and di-tert-butyl dicarbonate, and then adding diphenylphosphoryl azide dropwise to react to obtain (2-methoxy-6-methylpyridin-4-yl)carbamic acid tert-butyl ester (Compound 3); S1003, add tert-butyl (2-methoxy-6-methylpyridin-4-yl)carbamate obtained in step S1002 to organic solvent III, add hydrogen chloride organic solution, and react to obtain 2-methoxy-4-amino-6-methylpyridine (target 4).

[0023] Those skilled in the art can understand that, since 2-methoxy-6-methylpyridine-4-carboxylic acid is very expensive, preparing 2-methoxy-6-methylpyridine-4-carboxylic acid through the above step S1001 can effectively save preparation costs.

[0024] Preferably, in step S1001, during the reaction, at least one of the following conditions is satisfied: The reaction temperature is 80-200°C; and The reaction time is 2-6 hours.

[0025] Preferably, the organic solvent I is selected from one or more of dimethyl sulfoxide, dimethylformamide or dimethylacetamide.

[0026] Furthermore, in step S1001, the mass volume ratio of the 2-chloro-6-methylpyridine-4-carboxylic acid (Compound 1) to the organic solvent I is 1:(5-40) g / mL, and the molar ratio of the Compound 1 to the methoxide is 1:(2.00-5.00).

[0027] More preferably, after the reaction of step S1001 is completed and before step S1002 is performed, a first post-treatment is performed to obtain the 2-methoxy-6-methylpyridine-4-carboxylic acid, wherein the first post-treatment step comprises: S1101, cooling the reaction solution and adding ice water; S1102, adjust the pH of the reaction solution to 3-4 with an acidic aqueous solution, extract with an organic solvent IV, combine the organic phases, wash, dry, filter, and add petroleum ether for pulping to obtain 2-methoxy-6-methylpyridine-4-carboxylic acid.

[0028] Preferably, in step S1102, the acidic aqueous solution is selected from one or more of hydrochloric acid solution, sulfuric acid solution, nitric acid solution, and acetic acid solution.

[0029] Also preferably, in step S1102, the organic solvent IV is selected from one or more of ethyl acetate, butyl acetate, chloroform, toluene, dichloromethane, and dichloroethane.

[0030] Preferably, in step S1002, at least one of the following conditions is met: The molar ratio of the 2-methoxy-6-methylpyridine-4-carboxylic acid to triethylamine is 1:(1.00-3.00); The molar ratio of the 2-methoxy-6-methylpyridine-4-carboxylic acid to di-tert-butyl dicarbonate is 1:(1.00-5.00); The molar ratio of 2-methoxy-6-methylpyridine-4-carboxylic acid to diphenylphosphoryl azide is 1:(1.00-3.00); The mass volume ratio of the 2-methoxy-6-methylpyridine-4-carboxylic acid to the organic solvent II is 1:(5-40) g / mL; The reaction time is 10-200 hours; The reaction temperature is 70-200°C; The organic solvent II is selected from one or more of tert-butyl alcohol, ethanol or isopropanol.

[0031] Preferably, after the reaction in step S1002 is completed and before step S1003 is performed, a second post-treatment is performed to obtain tert-butyl (2-methoxy-6-methylpyridin-4-yl)carbamate; the second post-treatment comprises the steps of: S2101, after the reaction is completed, most of the solvent is concentrated under reduced pressure, and then water is added; S2102, extract with organic solvent V, combine the organic phases, wash, dry, filter, and spin dry to obtain tert-butyl (2-methoxy-6-methylpyridin-4-yl)carbamate.

[0032] Preferably, in step S2102, the organic solvent V is selected from one or more of ethyl acetate, butyl acetate, chloroform, toluene, dichloromethane, and dichloroethane.

[0033] Preferably, in step S1003, at least one of the following conditions is met: The hydrogen chloride organic solution is selected from one or more of hydrogen chloride ethyl acetate solution, hydrogen chloride 1,4-dioxane solution, and hydrogen chloride methanol solution; The organic solvent III is selected from one or more of ethyl acetate, 1,4-dioxane or methanol; The mass volume ratio of the (2-methoxy-6-methylpyridin-4-yl)carbamic acid tert-butyl ester to the organic solvent III is 1:(5-40) g / mL.

[0034] Preferably, in the step S1003, after adding the hydrogen chloride organic solution and reacting, the 2-methoxy-4-amino-6-methylpyridine is obtained by a third post-treatment, and the third post-treatment comprises the steps of: S3101, after the reaction is complete, filtering the reaction solution to obtain a solid; S3102, the solid is stirred with a mixed organic solvent of petroleum ether and ethyl acetate in a volume ratio of 10:1 for 20-50 minutes, then filtered, the solid is dissolved with water, the pH is adjusted to 8-9 with an alkaline aqueous solution, extracted with an organic solvent VII, the organic phases are combined, the organic phases are washed, dried, filtered, and spin-dried, and petroleum ether is added to pulp to obtain 2-methoxy-4-amino-6-methylpyridine.

[0035] Preferably, in step S3102, the alkaline aqueous solution is selected from one or more of sodium bicarbonate solution, sodium carbonate solution, potassium carbonate solution, sodium hydroxide solution, and potassium hydroxide solution.

[0036] Preferably, in step S3102, the organic solvent VII is selected from one or more of ethyl acetate, butyl acetate, chloroform, toluene, dichloromethane, and dichloroethane. Example

[0037] In this example, methoxy-4-amino-6-methylpyridine (Compound 4) was synthesized in the following steps: (1) Raw material 1, 2-chloro-6-methylpyridine-4-carboxylic acid (800.00 g, 4.66 mol, 1.00 eq) was added to dimethyl sulfoxide (8.0 L), and then sodium methoxide (629.72 g, 11.66 mol, 2.50 eq) was added, and the mixture was reacted at 100° C. for 2 hours. After the reaction was completed, the reaction solution was cooled, ice water (16.0 L) was added, and the pH of the reaction solution was adjusted to 3-4 with a 3M hydrochloric acid aqueous solution, and extracted with ethyl acetate three times (3.0 L×3), and the organic phases were combined, washed with water twice (2.0 L×3), washed with saturated brine once (2.0 L), and then dried with anhydrous sodium sulfate, filtered, and vortexed until a small amount of solvent remained, and then petroleum ether (4.0 L) was added to slurry to obtain 2-methoxy-6-methylpyridine-4-carboxylic acid (weight 723.60 g, purity 97%, yield 90%).

[0038] (2) Add 2-methoxy-6-methylpyridine-4-carboxylic acid (700.00 g, 4.19 mol, 1.00 eq) to tert-butyl alcohol (7.0 L), add triethylamine (466.12 g, 4.61 mol, 1.10 eq) and di-tert-butyl dicarbonate (2.28 kg, 10.47 mol, 2.50 eq), raise the temperature to 80°C and reflux, add diphenylphosphoryl azide (1.38 kg, 5.03 mol, 1.20 eq) dropwise, and after the addition is complete, keep the reaction at 80°C and reflux for 12 hours. After the reaction was completed, most of the solvent tert-butyl alcohol was concentrated under reduced pressure, and water (7.0 L) was added, and extracted with ethyl acetate three times (3.0 L×3). The organic phases were combined, washed with water twice (2.0 L×3), washed once with saturated brine (2.0 L), and then dried over anhydrous sodium sulfate, filtered, and spin-dried to obtain tert-butyl (2-methoxy-6-methylpyridin-4-yl)carbamate (weight 980.60 g, purity 96%, yield 94%).

[0039] (3) tert-Butyl (2-methoxy-6-methylpyridin-4-yl)carbamate (900.00 g, 3.78 mol, 1.00 eq) was added to ethyl acetate (4.5 L), and 4 M hydrogen chloride ethyl acetate solution (4.5 L) was added, and the mixture was stirred at room temperature for 12 hours. After the reaction is complete, the reaction solution is filtered to obtain a solid, and the solid is stirred with a mixed organic solvent (3.0 L) of petroleum ether: ethyl acetate in a ratio of 10:1 for 30 minutes, and then filtered. The solid is dissolved with water, the pH is adjusted to 8-9 with an aqueous potassium carbonate solution, and extracted with ethyl acetate three times (2.0 L×3), the organic phases are combined, the organic phases are washed twice with water (2.0 L×3), washed once with saturated brine (2.0 L), and then dried over anhydrous sodium sulfate, filtered, and spin-dried. Petroleum ether (2.0 L) is then added for slurrying to obtain the target methoxy-4-amino-6-methylpyridine (Compound 4), namely 2-methoxy-4-amino-6-methylpyridine (weight 498.90 g, purity 98%, yield 94%).

[0040] The H NMR spectrum of the obtained 2-methoxy-4-amino-6-methylpyridine (compound 4) is as follows Figure 1 The obtained characterization data are as follows: 1 H NMR (400 MHz, DMSO) δ 6.02 (d, J = 1.2 Hz, 1H), 5.79 (s, 2H), 5.63(d, J = 1.5 Hz, 1H), 3.69 (s, 3H), 2.16 (s, 3H).

[0041] Example 2-13 Example 2-13 is the same as Example 1, except that the triethylamine, di-tert-butyl dicarbonate, diphenylphosphoryl azide, organic solvent I, reaction temperature, reaction time, etc. in reaction step S1002 are adjusted, as shown in Table 1.

[0042] Through Examples 1-13, the effects of various reaction conditions on the reaction yield in the synthesis of intermediate compound 3 (tert-butyl (2-methoxy-6-methylpyridin-4-yl)carbamate) were investigated, and the reaction results are shown in Table 1.

[0043] Table 1

[0044] Combining the above charts, we can see that Comparing Examples 1-3, when the molar ratio of compound 2:triethylamine is 1.0:1.1, the reaction effect is already very good.

[0045] Comparing Examples 1, 4-5, when the molar ratio of compound 2: di-tert-butyl dicarbonate is 1.0:2.5, the reaction effect is already very good.

[0046] Comparing Examples 1, 6-7, when the molar ratio of compound 2: diphenylphosphoryl azide is 1.0:1.2, the reaction effect is already very good.

[0047] Comparing Examples 1, 8-9, the reaction can obtain the product in high yield in the solvents of tert-butanol, isopropanol and ethanol, among which tert-butanol has a better effect as a solvent.

[0048] Comparing Examples 1, 10-11, when the reaction temperature is 80°C, the reaction effect is already very good.

[0049] Comparing Examples 1, 12-13, when the reaction time is 12 hours, the reaction effect is already very good.

[0050] It should be understood by those skilled in the art that the embodiments of the present invention described above and shown in the accompanying drawings are only examples and do not limit the present invention. The advantages of the present invention have been fully and effectively achieved. The functional and structural principles of the present invention have been demonstrated and explained in the embodiments, and the embodiments of the present invention may be deformed or modified in any way without departing from the principles.

Claims

1. A method for synthesizing 2-methoxy-4-amino-6-methylpyridine, characterized in that: It includes the steps of: S1001, adding 2-chloro-6-methylpyridine-4-carboxylic acid to an organic solvent I, and then adding methoxide to react 2-chloro-6-methylpyridine-4-carboxylic acid to form 2-methoxy-6-methylpyridine-4-carboxylic acid; S1002, adding the 2-methoxy-6-methylpyridine-4-carboxylic acid prepared in step S1001 to the organic solvent II, then adding triethylamine and di-tert-butyl dicarbonate, and then adding diphenylphosphoryl azide dropwise to react to obtain (2-methoxy-6-methylpyridin-4-yl)carbamic acid tert-butyl ester; S1003, adding tert-butyl (2-methoxy-6-methylpyridin-4-yl)carbamate obtained in step S1002 to organic solvent III, and adding hydrogen chloride organic solution to react to obtain 2-methoxy-4-amino-6-methylpyridine.

2. The method for synthesizing 2-methoxy-4-amino-6-methylpyridine according to claim 1, characterized in that: In step S1001, at least one of the following conditions is met during the reaction: The methoxide is sodium methoxide; The reaction temperature is 80-200°C; The reaction time is 2-6 hours; The mass volume ratio of the 2-chloro-6-methylpyridine-4-carboxylic acid to the organic solvent I is 1:(5-40) g / mL; The molar ratio of 2-chloro-6-methylpyridine-4-carboxylic acid to methoxide is 1:(2.00-5.00); The organic solvent I is selected from one or more of dimethyl sulfoxide, dimethylformamide or dimethylacetamide.

3. The method for synthesizing 2-methoxy-4-amino-6-methylpyridine according to claim 1, characterized in that: After the reaction in step S1001 is completed and before the step S1002 is performed, the 2-methoxy-6-methylpyridine-4-carboxylic acid is obtained by a first post-treatment, wherein the first post-treatment step comprises: S1101, cooling the reaction solution and adding ice water; S1102, adjust the pH of the reaction solution to 3-4 with an acidic aqueous solution, extract with an organic solvent IV, combine the organic phases, wash, dry, filter, and add petroleum ether for pulping to obtain 2-methoxy-6-methylpyridine-4-carboxylic acid.

4. The method for synthesizing 2-methoxy-4-amino-6-methylpyridine according to claim 3, characterized in that: In step S1102, the acidic aqueous solution is selected from one or more of hydrochloric acid solution, sulfuric acid solution, nitric acid solution, and acetic acid solution; the organic solvent IV is selected from one or more of ethyl acetate, butyl acetate, chloroform, toluene, dichloromethane, and dichloroethane.

5. The method for synthesizing 2-methoxy-4-amino-6-methylpyridine according to claim 1, characterized in that: In step S1002, at least one of the following conditions is met: The molar ratio of the 2-methoxy-6-methylpyridine-4-carboxylic acid to triethylamine is 1:(1.00-3.00); The molar ratio of the 2-methoxy-6-methylpyridine-4-carboxylic acid to di-tert-butyl dicarbonate is 1:(1.00-5.00); The molar ratio of 2-methoxy-6-methylpyridine-4-carboxylic acid to diphenylphosphoryl azide is 1:(1.00-3.00); The mass volume ratio of the 2-methoxy-6-methylpyridine-4-carboxylic acid to the organic solvent II is 1:(5-40) g / mL; The reaction time is 10-200 hours; The reaction temperature is 70-200°C; The organic solvent II is selected from one or more of tert-butyl alcohol, ethanol or isopropanol.

6. The method for synthesizing 2-methoxy-4-amino-6-methylpyridine according to claim 1, characterized in that: After the reaction in step S1002 is completed and before step S1003 is performed, a second post-treatment is performed to obtain (2-methoxy-6-methylpyridin-4-yl)carbamic acid tert-butyl ester; the second post-treatment comprises the steps of: S2101, after the reaction is completed, most of the solvent is concentrated under reduced pressure, and then water is added; S2102, extract with organic solvent V, combine the organic phases, wash, dry, filter, and spin dry to obtain tert-butyl (2-methoxy-6-methylpyridin-4-yl)carbamate; In step S2102, the organic solvent V is selected from one or more of ethyl acetate, butyl acetate, chloroform, toluene, dichloromethane, and dichloroethane.

7. The method for synthesizing 2-methoxy-4-amino-6-methylpyridine according to claim 1, characterized in that: In the step S1003, after adding hydrogen chloride organic solution for reaction, the 2-methoxy-4-amino-6-methylpyridine is obtained through a third post-treatment, wherein the third post-treatment comprises the steps of: S3101, after the reaction is complete, filtering the reaction solution to obtain a solid; S3102, the solid is stirred with a mixed organic solvent of petroleum ether and ethyl acetate in a volume ratio of 10:1 for 20-50 minutes, then filtered, the solid is dissolved with water, the pH is adjusted to 8-9 with an alkaline aqueous solution, extracted with an organic solvent VII, the organic phases are combined, the organic phases are washed, dried, filtered, and spin-dried, and petroleum ether is added to pulp to obtain 2-methoxy-4-amino-6-methylpyridine.

8. The method for synthesizing 2-methoxy-4-amino-6-methylpyridine according to claim 7, characterized in that: In step S3102, the alkaline aqueous solution is selected from one or more of sodium bicarbonate solution, sodium carbonate solution, potassium carbonate solution, sodium hydroxide solution, and potassium hydroxide solution; In step S3102, the organic solvent VII is selected from one or more of ethyl acetate, butyl acetate, chloroform, toluene, dichloromethane, and dichloroethane.

9. The method for synthesizing 2-methoxy-4-amino-6-methylpyridine according to claim 1, characterized in that: In step S1003, at least one of the following conditions is met: The hydrogen chloride organic solution is selected from one or more of hydrogen chloride ethyl acetate solution, hydrogen chloride 1,4-dioxane solution, and hydrogen chloride methanol solution; The organic solvent III is selected from one or more of ethyl acetate, 1,4-dioxane or methanol; The mass volume ratio of the (2-methoxy-6-methylpyridin-4-yl)carbamic acid tert-butyl ester to the organic solvent III is 1:(5-40) g / mL.

10. A 2-methoxy-4-amino-6-methylpyridine, characterized in that: The method is based on the synthesis method of 2-methoxy-4-amino-6-methylpyridine as claimed in any one of claims 1 to 9.

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