CN115073454B - Imidazo pyridine-2-oxazoline compound and preparation method and application thereof - Google Patents

Abstract

The invention belongs to the technical field of drug active compound discovery, and particularly relates to an imidazopyridine-2-oxazoline compound, and a preparation method and application thereof. The imidazopyridine-2-oxazoline compound or the chemically acceptable salt thereof provided by the invention has strong activity inhibition effect on agricultural harmful pathogenic bacteria, especially plant fungal diseases, has low production cost, has positive significance on the creation of new pesticides, and is particularly suitable for the control of diseases such as sheath blight germ, rhizoctonia cerealis, sclerotinia sclerotiorum, gibberella cerealis, wheat take-all germ, botrytis cinerea, potato late blight germ, phytophthora capsici, tomato early blight germ, rice oxa Miao Bingjun, potato dry rot germ, cucumber anthracnose germ, rice blast germ and the like.

Description

An imidazopyridine-2-oxazoline compound and its preparation method and application

Technical Field

The invention belongs to the technical field of pharmaceutically active compounds, and specifically relates to an imidazopyridine-2-oxazoline compound and a preparation method and application thereof.

Background Art

At present, in agricultural production, pesticides play an important role in preventing and controlling agricultural pests and ensuring high-quality and high-yield food. Among them, chemical pesticides account for more than 80% of the total and are the main method for preventing and controlling pests. However, the abuse of pesticides and the use of ineffective isomers will cause many environmental problems and waste of resources, such as pesticide residues, residual toxicity, and increased resistance of pests. Therefore, the research and synthesis of new environmentally friendly and economical pesticides is an important topic in the process of agricultural modernization.

The discovery of chemical small molecule pesticides with completely new structures provides a new approach to solving the above problems and is also a direction that needs to be explored urgently in the field of plant chemical protection. Currently, there are no reports on compounds with an imidazopyridine-2-oxazoline skeleton.

Summary of the invention

The purpose of the present invention is to provide an imidazopyridine-2-oxazoline compound and a preparation method and application thereof. The imidazopyridine-2-oxazoline compound provided by the present invention basically does not cause drug resistance of agricultural harmful pathogens, has a strong active inhibitory effect on agricultural harmful pathogens, is environmentally friendly, and has low production cost.

In order to achieve the above object, the present invention provides the following technical solutions:

The present invention provides an imidazopyridine-2-oxazoline compound or a pesticide chemically acceptable salt thereof, wherein the structure of the imidazopyridine-2-oxazoline compound is as shown in Formula I:

In the formula I, the carbon center configuration substituted by R ₁ and R ₂ is independently R-type or S-type;

The _R1 includes a hydrocarbon group, a phenyl group, a substituted phenyl group, a benzyl group, a substituted benzyl group, a hydroxymethylene group, a substituted hydrocarbon oxymethylene group, a carboxylic acid group, an ester group, a substituted ester group, a hydrocarbon carbonyl group, a phenylcarbonyl group, a substituted phenylcarbonyl group or a substituted hydroxymethyl group;

The R ₂ includes hydrogen, alkyl, hydroxymethylene, ester, substituted ester, aromatic or aromatic methylene;

The R ₃ includes hydrogen, halogen, alkyl, alkoxy, cyclohexyl, aromatic, substituted aromatic, aromatic methylene, phenoxy, substituted phenoxy, anilino, substituted anilino, alkylcarbonyl or substituted methyl.

Preferably, when R ₃ in Formula I is a substituted phenyl group, the structure of the imidazopyridine-2-oxazoline compound is as shown in Formula II:

In formula II: R ₄ includes halogen, C ₁ ～C ₆ hydrocarbon group, C ₁ ～C ₆ hydrocarbonoxy group, C ₁ ～C ₆ hydrocarbonamino group, nitro group or ester group;

Preferably, when R ₃ in Formula I is a phenoxy group or a substituted phenoxy group, the structure of the imidazopyridine-2-oxazoline compound is as shown in Formula III:

In formula III: R ₅ includes hydrogen, halogen, C ₁ ～C ₆ hydrocarbon group, C ₁ ～C ₆ hydrocarbonoxy group, C ₁ ～C ₆ hydrocarbonamino group, nitro group or ester group;

Preferably, when R ₃ in Formula I is phenylamino or substituted phenylamino, the structure of the imidazopyridine-2-oxazoline compound is as shown in Formula IV:

In formula IV: the R ₆ includes hydrogen, halogen, C ₁ ～C ₆ hydrocarbon group, C ₁ ～C ₆ hydrocarbonoxy group, C ₁ ～C ₆ hydrocarbonamino group, nitro group or ester group.

Preferably, the structural formula of the imidazopyridine-2-oxazoline compound is one of Formula A1 to Formula A10:

The present invention also provides a method for preparing the imidazopyridine-2-oxazoline compound described in the above scheme, comprising the following steps:

(1) mixing a substituted 2-aminopyridine, a pyruvate ester and a first organic solvent and subjecting them to a reflux reaction to obtain an intermediate A; the structure of the substituted 2-aminopyridine is shown in Formula V, and the structure of the intermediate A is shown in Formula VI:

(2) The intermediate A, an alkali metal hydroxide and a second organic solvent are mixed and subjected to a hydrolysis reaction to obtain an intermediate B; the structure of the intermediate B is shown in Formula VII:

(3) The intermediate B, a condensing agent, 1-hydroxybenzotriazole, a chiral amino alcohol and a third organic solvent are mixed for condensation reaction to obtain an intermediate C; the structure of the chiral amino alcohol is shown in Formula VIII, and the structure of the intermediate C is shown in Formula IX:

(4) The intermediate C, diethylaminosulfur trifluoride and a fourth organic solvent are mixed to carry out a ring-forming reaction to obtain an imidazopyridine-2-oxazoline compound having a structure shown in formula I.

The present invention also provides a method for preparing the imidazopyridine-2-oxazoline compound of the structure shown in Formula II of the imidazopyridine-2-oxazoline compound described in the above scheme, comprising the following steps:

The compound of the structure shown in formula X, tetrakis(triphenylphosphine)palladium, the substituted phenylboronic acid of the structure shown in formula XI, potassium carbonate and the fifth organic solvent are mixed to carry out SUZUKI coupling reaction to obtain the imidazopyridine-2-oxazoline compound of the structure shown in formula II:

The present invention also provides a method for preparing the imidazopyridine-2-oxazoline compound of the structure shown in formula III in the imidazopyridine-2-oxazoline compound described in the above scheme, comprising the following steps:

The compound of the structure shown in formula X, cuprous iodide, N,N-dimethylglycine, cesium carbonate, the substituted phenol of the structure shown in formula XII and the sixth organic solvent are mixed to carry out Ullmann coupling reaction to obtain an imidazopyridine-2-oxazoline compound of the structure shown in formula III:

The present invention also provides a method for preparing the imidazopyridine-2-oxazoline compound of the structure shown in Formula IV of the imidazopyridine-2-oxazoline compound described in the above scheme, comprising the following steps:

The compound represented by the structure of formula X, cuprous iodide, cis-1,2-cyclohexanediamine, potassium carbonate, the substituted aniline represented by the structure of formula XIII and the seventh organic solvent are mixed to carry out Ullmann reaction to obtain an imidazopyridine-2-oxazoline compound represented by the structure of formula IV:

Preferably, the molar ratio of the substituted 2-aminopyridine to the pyruvate in step (1) is 1:1.5-3; the molar ratio of the intermediate B to the chiral amino alcohol in step (3) is 1:1-3; the molar ratio of the intermediate B to the condensing agent is 1:1.2-3; the molar ratio of the intermediate B to 1-hydroxybenzotriazole is 1:1.2-5; the molar ratio of the intermediate C to diethylaminosulfur trifluoride in step (4) is 1:3-6.

Preferably, the temperature of the reflux reaction in step (1) is 30 to 100°C, and the time is 6 to 24 hours; the temperature of the hydrolysis reaction in step (2) is 0 to 80°C, and the time is 6 to 72 hours; the temperature of the condensation reaction in step (3) is 0 to 40°C, and the time is 12 to 96 hours; the temperature of the cyclization reaction in step (4) is -5 to 25°C, and the time is 0.5 to 14 hours.

The present invention also provides the use of the imidazopyridine-2-oxazoline compounds or their pesticide chemically acceptable salts described in the above scheme in the prevention and treatment of agricultural harmful pathogens.

The present invention provides an imidazopyridine-2-oxazoline compound or a pesticide chemically acceptable salt thereof, wherein the structure of the imidazopyridine-2-oxazoline compound is shown in Formula I. The imidazopyridine-2-oxazoline compound provided by the present invention has a strong active inhibitory effect on agricultural harmful pathogens, especially plant fungal diseases, and basically does not cause drug resistance of agricultural harmful pathogens. It is environmentally friendly, easy to use, and has low production cost, and has positive significance for the creation of new pesticides.

The present invention also provides a method for preparing the imidazopyridine-2-oxazoline compounds described in the above scheme, and designs and synthesizes a series of imidazopyridine-2-oxazoline compounds. The preparation method provided by the present invention has easy-to-obtain raw materials, simple steps, strong operability, low cost, and environmental friendliness, and has the prospect of large-scale industrial application.

The present invention also provides the use of the imidazopyridine-2-oxazoline compounds or their pesticide chemically acceptable salts described in the above scheme in the prevention and treatment of agricultural harmful pathogens. The imidazopyridine-2-oxazoline compounds provided by the present invention can produce strong active inhibition on agricultural harmful pathogens, especially better inhibition effect on plant fungal diseases, especially for the prevention and treatment of rice sheath blight, wheat sheath blight, rapeseed sclerotinia, wheat head blight, wheat take-all, tomato gray mold, potato late blight, pepper phytophthora, tomato early blight, rice seedling pathogen, potato dry rot, cucumber anthracnose and rice blast, and have more excellent prevention and treatment effect.

DETAILED DESCRIPTION

The present invention provides an imidazopyridine-2-oxazoline compound or a pesticide chemically acceptable salt thereof, wherein the structure of the imidazopyridine-2-oxazoline compound is as shown in Formula I:

In the formula I, the carbon center configuration substituted by R ₁ and R ₂ is independently R-type or S-type;

The _R1 includes a hydrocarbon group, a phenyl group, a substituted phenyl group, a benzyl group, a substituted benzyl group, a hydroxymethylene group, a substituted hydrocarbon oxymethylene group, a carboxylic acid group, an ester group, a substituted ester group, a hydrocarbon carbonyl group, a phenyl carbonyl group, a substituted phenyl carbonyl group or a substituted hydroxymethyl group;

The R ₂ includes hydrogen, alkyl, hydroxymethylene, ester, substituted ester, aromatic or aromatic methylene;

The R ₃ includes hydrogen, halogen, alkyl, alkoxy, cyclohexyl, aromatic, substituted aromatic, aromatic methylene, phenoxy, substituted phenoxy, anilino, substituted anilino, alkylcarbonyl or substituted methyl.

In the present invention, when _R1 in Formula I is a hydrocarbon group, the hydrocarbon group is preferably a _C1 - _C8 hydrocarbon group; when _R1 is a substituted phenyl group, the substituent in the substituted phenyl group preferably includes a _C1 - _C6 hydrocarbon group, a _C1 - _C6 hydrocarbonoxy group or a _C1 - _C6 halogenated hydrocarbon group, and the number of substituents in the substituted phenyl group is preferably 1-5, more preferably 2-4; when _R1 is a substituted benzyl group, the substitution site of the substituent in the substituted benzyl group is preferably a benzene ring, the substituent in the substituted benzyl group preferably includes a _C1 - _C6 hydrocarbon group, a _C1 - _C6 hydrocarbonoxy group or a _C1 - _C6 halogenated hydrocarbon group, and the number of substituents in the substituted benzyl group is preferably 1-5, more preferably 2-3; when _R1 is a substituted ester group, the substituent in the substituted ester group preferably includes one or more of a carboxylic acid and a hydrocarbon group, and the hydrocarbon group is preferably a _C1 - _C6 hydrocarbon group; When _R1 is a hydrocarbylcarbonyl group, the hydrocarbyl in the hydrocarbylcarbonyl group is preferably a _C1 - _C6 hydrocarbyl group; when _R1 is a substituted phenylcarbonyl group, the substitution site of the substituent in the substituted phenylcarbonyl group is preferably a benzene ring, the substituent in the substituted phenylcarbonyl group preferably includes a _C1 - _C6 hydrocarbyl group, a _C1 - _C6 hydrocarbyloxy group or a _C1 - _C6 halogenated hydrocarbyl group, and the number of the substituent in the substituted phenylcarbonyl group is preferably 1-5, more preferably 2-5; when _R1 is a substituted hydrocarbyloxymethylene group, the substituent of the substituted hydrocarbyloxymethylene group preferably includes a _C1 - _C6 hydrocarbyl group, a phenyl group, a _C1 - _C6 hydrocarbyl-substituted phenyl group, a _C1 - _C6 hydrocarbyloxy-substituted phenyl group or a _C1 - _C6 halogenated hydrocarbyl-substituted phenyl group.

In the present invention, when _R2 in Formula I is an alkyl group, the alkyl group is preferably a _C1 - _C4 alkyl group, more preferably a methyl group, an ethyl group, an isopropyl group, a sec-butyl group or an isobutyl group; when _R2 is a substituted ester group, the substituent in the substituted ester group preferably includes one or more of a carboxylic acid and a hydrocarbon group, the hydrocarbon group is preferably a _C1 - _C6 hydrocarbon group, and the number of substituents in the substituted ester group is preferably 1-6, more preferably 1-2; when _R2 is an aromatic group, the aromatic group is preferably a phenyl group; when _R2 is an aromatic methylene group, the aromatic group in the aromatic methylene group is preferably a benzyl group.

In the present invention, when _R3 in Formula I is an alkyl group, the alkyl group is preferably a _C1 - _C6 alkyl group; when _R3 is an alkoxy group, the alkoxy group is preferably a _C1 - _C6 alkoxy group; when _R3 is an aromatic group, the aromatic group is preferably a phenyl group; when _R3 is a substituted aromatic group, the substituted aromatic group is preferably a substituted phenyl group; when _R3 is a substituted aromatic group, the substituent in the substituted aromatic group preferably includes halogen, _C1 - _C6 hydrocarbon group, _C1 - _C6 hydrocarbonoxy group, _C1 - _C6 hydrocarbonamino group, nitro group or ester group, and the number of substituents in the substituted aromatic group is preferably 1-6, more preferably 1-3; when _R3 is a substituted phenoxy group, the substitution site of the substituent in the substituted phenoxy group is preferably a benzene ring, and the substituent in the substituted phenoxy group preferably includes halogen, _C1 - _C6 hydrocarbon group, C1-C6 hydrocarbonoxy group, _C1 - _C6 hydrocarbonamino group, nitro _group or ester group. wherein the number of substituents in the substituted phenyloxy group is preferably 1 to 3, and more preferably 2; when the R ₃ is a substituted phenylamino group, the substitution site of the substituent in the substituted phenylamino group is preferably 3 to ₆ , and the substituent in the substituted phenylamino group preferably includes halogen, C ₁ to C ₆ alkyl, C ₁ to C ₆ alkyloxy, C ₁ to C ₆ alkylamino, nitro or ester group, and the number of substituents in the substituted phenylamino group is preferably 1 to 6, and more preferably 1 to 3; when the R ₃ is an alkylcarbonyl group, the alkyl group in the alkylcarbonyl group preferably includes one or both of methyl and ethyl; when the R ₃ is a substituted methyl group, the substituent in the substituted methyl group preferably includes halogen, alkoxy or aromatic group, and the number of substituents in the substituted methyl group is preferably 1 to 6, and more preferably 1 to 3.

In the present invention, when R ₃ in Formula I is a substituted phenyl group, the structure of the imidazopyridine-2-oxazoline compound is preferably as shown in Formula II:

In formula II: R ₄ preferably includes halogen, C ₁ ～C ₆ hydrocarbon group, C ₁ ～C ₆ hydrocarbonoxy group, C ₁ ～C ₆ hydrocarbonamino group, nitro group or ester group;

When R ₃ in Formula I is a phenoxy group or a substituted phenoxy group, the structure of the imidazopyridine-2-oxazoline compound is preferably as shown in Formula III:

In formula III: the R ₅ preferably includes hydrogen, halogen, C ₁ ～C ₆ hydrocarbon group, C ₁ ～C ₆ hydrocarbonoxy group, C ₁ ～C ₆ hydrocarbonamino group, nitro group or ester group;

When R ₃ in Formula I is phenylamino or substituted phenylamino, the structure of the imidazopyridine-2-oxazoline compound is preferably as shown in Formula IV:

In formula IV: the R ₆ preferably includes hydrogen, halogen, C ₁ ～C ₆ hydrocarbon group, C ₁ ～C ₆ hydrocarbonoxy group, C ₁ ～C ₆ hydrocarbonamino group, nitro group or ester group.

In the present invention, the structural formula of the imidazopyridine-2-oxazoline compound is preferably one of Formula A1 to Formula A10:

The present invention also provides a pesticide chemically acceptable salt of an imidazopyridine-2-oxazoline compound. In the present invention, the pesticide chemically acceptable salt of the imidazopyridine-2-oxazoline compound is preferably an inorganic salt, and the inorganic salt preferably includes one or more of potassium salt, sodium salt, ammonium salt, calcium salt, pyridinium salt, hydrochloride, acetate, benzenesulfonate and oxalate.

The present invention also provides a method for preparing the imidazopyridine-2-oxazoline compound described in the above scheme, comprising the following steps:

(1) mixing a substituted 2-aminopyridine, a pyruvate ester and a first organic solvent and subjecting them to a reflux reaction to obtain an intermediate A; the structure of the substituted 2-aminopyridine is shown in Formula V, and the structure of the intermediate A is shown in Formula VI:

(2) The intermediate A, an alkali metal hydroxide and a second organic solvent are mixed and subjected to a hydrolysis reaction to obtain an intermediate B; the structure of the intermediate B is shown in Formula VII:

(3) The intermediate B, a condensing agent, 1-hydroxybenzotriazole, a chiral amino alcohol and a third organic solvent are mixed for condensation reaction to obtain an intermediate C; the structure of the chiral amino alcohol is shown in Formula VIII, and the structure of the intermediate C is shown in Formula IX:

(4) The intermediate C, diethylaminosulfur trifluoride and a fourth organic solvent are mixed to carry out a ring-forming reaction to obtain an imidazopyridine-2-oxazoline compound having a structure shown in formula I.

In the present invention, the synthesis route of the imidazopyridine-2-oxazoline compound of the structure shown in formula I (except the imidazopyridine-2-oxazoline compound of the structure shown in formula II, III and IV) is as shown below:

In the present invention, substituted 2-aminopyridine, pyruvate and a first organic solvent are mixed and subjected to reflux reaction to obtain an intermediate A. In the present invention, the molar ratio of the substituted 2-aminopyridine to the pyruvate is preferably 1:1.5-3, more preferably 1:2-3, and further preferably 1:2-2.5; the molar volume ratio of the substituted 2-aminopyridine to the first organic solvent is preferably 1 mol:3-10 mL, more preferably 1 mol:4-7 mL, and further preferably 1 mol:5 mL; the pyruvate preferably includes one or more of 3-bromopyruvate methyl ester, 3-bromopyruvate propyl ester and 3-bromopyruvate ethyl ester; the first organic solvent preferably includes alcohol or an alcohol-acid mixture, and the alcohol preferably includes one or more of ethanol, n-butanol and methanol; the acid in the alcohol-acid mixture is preferably acetic acid; when the first organic solvent is an ethanol-acetic acid mixture, the volume ratio of ethanol to acetic acid is preferably 1:0.5; the mixing is preferably stirring; the reflux reaction is preferably carried out under stirring; the present invention has no special requirements for the stirring, and conventional operations in the art can be used; the temperature of the reflux reaction is preferably 80°C, and the time is preferably 6-24h, more preferably 12-18h. In a specific embodiment of the present invention, the substituted 2-aminopyridine is preferably dissolved in ethanol, and then ethyl 3-bromopyruvate is added to carry out a reflux reaction.

In the present invention, after the reflux reaction is completed, post-treatment is preferably performed; the post-treatment preferably includes: removing the solvent from the mixture obtained by the reflux reaction to obtain a solid product, mixing the solid product and a quencher, and then extracting, drying and column chromatography in sequence to obtain an intermediate A; the solvent removal is preferably vacuum distillation; the present invention has no special requirements for the vacuum distillation, and conventional operations in the art can be used; the quencher preferably includes one or more of sodium bicarbonate solution, water and ammonium hydroxide solution. When the quencher is sodium bicarbonate solution or ammonium hydroxide solution, the concentration of the quencher is preferably 1 to 50%. 50wt%, more preferably 20-50wt%; the molar volume ratio of the substituted 2-aminopyridine and the quencher is preferably 1mmol:0.2-1mL, more preferably 1mmol:0.5-1mL; the extractant used in the extraction preferably includes ethyl acetate or dichloromethane; the drying preferably uses anhydrous sodium sulfate; the filler of the column chromatography is preferably silica column chromatography silica gel, the elution is preferably gradient elution, the eluent used for the elution preferably includes ethyl acetate and petroleum ether, and the volume ratio of ethyl acetate and petroleum ether is preferably 1:1-15, more preferably 1:5-12.

After obtaining the intermediate A, the present invention mixes the intermediate A, an alkali metal hydroxide and a second organic solvent for hydrolysis reaction to obtain the intermediate B. In the present invention, the molar ratio of the intermediate A to the alkali metal hydroxide is preferably 1:1.1-3, more preferably 1:1.5-2.5; the mass volume ratio of the alkali metal hydroxide to the second organic solvent is preferably 1:3-20, more preferably 1:5-10; the alkali metal hydroxide includes one or more of potassium hydroxide, sodium hydroxide and lithium hydroxide; the second organic solvent is preferably an alcohol, and the alcohol preferably includes one or two of methanol and ethanol; the hydrolysis reaction is preferably carried out under stirring; the present invention has no special requirements for the stirring, and conventional operations in the art can be used; the temperature of the hydrolysis reaction is preferably 25-80°C, more preferably 20-60°C, and further preferably 30-50°C, and the time is preferably 6-72h, more preferably 24-48h.

In the present invention, after the hydrolysis reaction is completed, post-treatment is preferably performed; the post-treatment preferably includes: adding the solid product obtained by removing the solvent from the mixture obtained by the hydrolysis reaction into water, adjusting the pH value of the obtained solution to 5-6, and then filtering to obtain intermediate B; the solvent removal is preferably concentration; the present invention has no special requirements for the concentration, and conventional operations in the field can be used.

After obtaining the intermediate B, the present invention mixes the intermediate B, a condensation agent, 1-hydroxybenzotriazole, a chiral amino alcohol and a third organic solvent to carry out a condensation reaction to obtain an intermediate C. In the present invention, the molar ratio of the intermediate B to the condensing agent is preferably 1:1-3, more preferably 1:1.3-2; the molar ratio of the intermediate B to 1-hydroxybenzotriazole is preferably 1:1.2-5, more preferably 1:2-3; the molar ratio of the intermediate B to the chiral amino alcohol is preferably 1:1.3-2, more preferably 1:1.3-1.5; the molar volume ratio of the intermediate B to the third organic solvent is preferably 1mmol:3-6mL, more preferably 1mmol:4-5mL; the condensing agent preferably includes 2-(7-azabenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU), O-benzotriazole-tetramethyluronium hexafluorophosphate (HBTU), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide salt one or more of edionyl chloride (EDCI) and 1-hydroxybenzotriazole (HOBT); the type of the chiral amino alcohol is selected according to the structure of the target product, preferably including one or more of (s)-tert-leucinol, isoleucinol, leucinol, phenylglycinol, 2-amino-1-butanol and 2-amino-1,2-diphenylethanol; the third organic solvent preferably includes one or more of anhydrous dichloromethane, tetrahydrofuran, dioxane, toluene and chlorobenzene; the condensation reaction is preferably carried out under stirring; the present invention has no special requirements for the stirring, and conventional operations in the art can be used; the temperature of the condensation reaction is preferably 0-40°C, more preferably 10-30°C, further preferably 15-25°C, and the time is preferably 12-96h, more preferably 36-72h. In a specific embodiment of the present invention, the intermediate B is preferably dissolved in a third organic solvent to obtain a mixed solution, and then a condensing agent, 1-hydroxybenzotriazole (HOBt) and a chiral amino alcohol are sequentially added to the mixed solution under ice bath conditions to carry out a condensation reaction.

In the present invention, after the condensation reaction is completed, post-treatment is preferably performed; the post-treatment preferably includes: adding a quencher to the mixture obtained by the condensation reaction to quench the reaction, and then washing with water, desolventizing and column chromatography are performed in sequence to obtain intermediate C; the quencher preferably includes one or more of sodium bicarbonate solution, ammonium chloride solution, sodium bicarbonate solution and sodium carbonate solution; the concentration of the quencher is preferably 10-50wt%, more preferably 20-40wt%; the molar volume ratio of the intermediate B and the quencher is 1mmol:2-10mL, more preferably 1mmol:4-8mL; the present invention has no special requirements for the desolventizing, and conventional operations in the art can be used; the filler of the column chromatography is preferably silica column chromatography silica gel, the elution is preferably gradient elution, and the eluent used for the elution preferably includes ethyl acetate and petroleum ether, and the volume ratio of ethyl acetate to petroleum ether is preferably 1:0.5-15, more preferably 1:3-12.

After obtaining the intermediate C, the present invention mixes the intermediate C, diethylaminosulfur trifluoride and the fourth organic solvent for a ring-forming reaction to obtain an imidazopyridine-2-oxazoline compound of the structure shown in formula I. In the present invention, the molar ratio of the intermediate C and diethylaminosulfur trifluoride is preferably 1:3-6, more preferably 1:3-5, and further preferably 1:4-5; the molar volume ratio of the intermediate C and the fourth organic solvent is preferably 1mmol:1-3mL, more preferably 1mmol:1.5-2.5mL; the fourth organic solvent preferably includes a halogenated hydrocarbon, and the halogenated hydrocarbon is preferably dichloromethane; the ring-forming reaction is preferably carried out under stirring, and the stirring is preferably magnetic stirring; the present invention has no special requirements for the magnetic stirring, and conventional operations in the art can be used; the temperature of the ring-forming reaction is preferably -5-25°C, more preferably -1-20°C, and further preferably 5-15°C, and the time is preferably 0.5-14h, more preferably 2-10h. In a specific embodiment of the present invention, the intermediate C is preferably added into a Shrek tube equipped with a magnetic stirrer, filled with protective gas, and a fourth organic solvent is added to dissolve, and then the mixture is transferred to 0-78°C and diethylaminosulfur trifluoride (DAST=3-6) is slowly added dropwise, and after the addition is completed, the mixture is stirred at -78°C and the cyclization reaction is carried out by TLC tracking monitoring; the protective gas is preferably N ₂ , and the number of times the protective gas is filled is preferably 3 times or more, more preferably 3 times; the rate of the slow addition is preferably 30-60 drops/min, more preferably 40-50 drops/min.

In the present invention, after the cyclization reaction is completed, post-treatment is preferably performed; the post-treatment preferably includes: mixing the mixed solution obtained by the cyclization reaction with water to quench the reaction, and then washing, drying and concentrating the organic phase in sequence, and performing column chromatography on the obtained solid product to obtain an imidazopyridine-2-oxazoline compound with a structure shown in formula I; the quenching agent is preferably water; the solution used for washing is preferably a sodium carbonate solution; the reagent used for drying the organic phase is preferably one or both of anhydrous sodium sulfate and anhydrous magnesium sulfate; the column chromatography device is preferably a silica gel chromatographic column, and the particle size of the silica gel is preferably 200 to 300 meshes.

The present invention also provides a method for preparing an imidazopyridine-2-oxazoline compound of the structure shown in formula II in the imidazopyridine-2-oxazoline compound of the above scheme, comprising the following steps: mixing a compound of the structure shown in formula X, tetrakis(triphenylphosphine)palladium, a substituted phenylboronic acid of the structure shown in formula XI, potassium carbonate and a fifth organic solvent to carry out a SUZUKI coupling reaction to obtain an imidazopyridine-2-oxazoline compound of the structure shown in formula II:

In the present invention, the reaction process of the SUZUKI coupling reaction is shown in the following formula:

In the present invention, the fifth organic solvent is preferably one or more of toluene, dioxane, dimethyl sulfoxide, xylene and N,N-dimethylformamide; the molar ratio of the compound of the structure represented by formula X to the substituted phenylboronic acid of the structure represented by formula XI is preferably 1:1.5-3, more preferably 1:2-3, and further preferably 1:2-2.5; the compound of the structure represented by formula X and tetrakis(triphenylphosphine)palladium(Pd(PPh ₃ ) ₄ ) is preferably 1:0.05-0.1, more preferably 1:0.07-0.09; the molar ratio of the compound represented by the structure of formula X to potassium carbonate is preferably 1:1-4, more preferably 1:2-3; the SUZUKI coupling reaction is preferably carried out under stirring and reflux conditions; the present invention has no special requirements for the stirring and reflux, and conventional operations in the art can be used; the temperature of the SUZUKI coupling reaction is preferably 100-110°C, more preferably 104-107°C, and the time is preferably 24-96h, more preferably 48-72h.

In the present invention, after the SUZUKI coupling reaction is completed, post-treatment is preferably performed; the post-treatment preferably includes: concentrating the mixed solution obtained by the SUZUKI coupling reaction, and then performing column chromatography on the obtained solid product to obtain a compound with an imidazopyridine-2-oxazoline structure shown in formula II; the column chromatography device is preferably a silica gel chromatographic column, and the particle size of the silica gel is preferably 200 to 300 meshes.

The present invention also provides a method for preparing an imidazopyridine-2-oxazoline compound of the structure shown in formula III of the imidazopyridine-2-oxazoline compound described in the above scheme, comprising the following steps: mixing a compound of the structure shown in formula X, cuprous iodide, N,N-dimethylglycine, cesium carbonate, a substituted phenol of the structure shown in formula XII and a sixth organic solvent to perform an Ullmann coupling reaction to obtain an imidazopyridine-2-oxazoline compound of the structure shown in formula III:

In the present invention, the reaction formula of the Ullmann coupling reaction is shown below:

In the present invention, the sixth organic solvent is preferably one or more of dioxane, dimethyl sulfoxide, xylene and N,N-dimethylformamide; the molar ratio of the compound of the structure represented by formula X to the substituted phenol of the structure represented by formula XII is preferably 1:1.5-3, more preferably 1:2-3, and further preferably 1:2.5-3; the molar ratio of the compound of the structure represented by formula X to cuprous iodide is preferably 1:0.1-0.5, more preferably 1:0.2-0.4; the molar ratio of the compound of the structure represented by formula X to N,N-dimethylglycine is preferably 1:0.1-0.5, more preferably 1:0.2-0.4; the molar ratio of the compound of the structure shown in formula X to cesium carbonate is preferably 1:0.1-0.5, more preferably 1:0.2-0.4; the Ullmann coupling reaction is preferably carried out under stirring and reflux conditions; the present invention has no special requirements for the stirring and reflux, and conventional operations in the art can be used; the temperature of the Ullmann coupling reaction is preferably 100-110°C, more preferably 103-106°C, and the time is preferably 24-96h, more preferably 48-60h. In a specific embodiment of the present invention, the compound of the structure shown in formula X, cuprous iodide, N,N-dimethylglycine (DMG), cesium carbonate and the substituted phenol of the structure shown in formula XII are preferably added to a Shrek tube, and then a protective gas is introduced, and then a sixth organic solvent is added to carry out an Ullmann coupling reaction; the number of times the protective gas is introduced is preferably 3 times or more, more preferably 3 times; the protective gas is preferably N ₂ .

In the present invention, after the Ullmann coupling reaction is completed, post-treatment is preferably performed; the post-treatment preferably includes: concentrating the mixed solution obtained by the Ullmann coupling reaction, and then performing column chromatography on the obtained solid product to obtain an imidazopyridine-2-oxazoline compound with a structure shown in formula III; the column chromatography device is preferably a silica gel chromatographic column, and the particle size of the silica gel is preferably 200 to 300 meshes.

The present invention also provides a method for preparing an imidazopyridine-2-oxazoline compound of the structure shown in formula IV of the imidazopyridine-2-oxazoline compound described in the above scheme, comprising the following steps: mixing a compound of the structure shown in formula X, cuprous iodide, cis-1,2-cyclohexanediamine, potassium carbonate, a substituted aniline of the structure shown in formula XIII and a seventh organic solvent to perform an Ullmann reaction to obtain an imidazopyridine-2-oxazoline compound of the structure shown in formula IV:

In the present invention, the reaction formula of the Ullmann reaction is shown below:

In the present invention, the seventh organic solvent is preferably one or more of dioxane, toluene and xylene; the molar ratio of the compound of the structure represented by formula X to the substituted aniline of the structure represented by formula XIII is preferably 1:1.5-3, more preferably 1:1.5-2.5, and further preferably 1:2-2.5; the molar ratio of the compound of the structure represented by formula X to cuprous iodide is preferably 1:0.1-0.4, more preferably 1:0.1-0.3, and further preferably 1:0.1; the molar ratio of the compound of the structure represented by formula X to cis-1,2-cyclohexanediamine is preferably 1:0. 2～0.8, more preferably 1:0.2～0.5, further preferably 1:0.2～0.3; the molar ratio of the compound of the structure shown in formula X to potassium carbonate is preferably 1:1～5, more preferably 1:2～4, more preferably 1:2; the Ullmann reaction is preferably carried out under stirring and reflux conditions; the present invention has no special requirements for the stirring and reflux, and conventional operations in the art can be used; the temperature of the Ullmann reaction is preferably 100～120℃, more preferably 105～115℃, and the time is preferably 24～96h, more preferably 48～72h. In a specific embodiment of the present invention, it is preferred to add the compound of the structure shown in formula X, cuprous iodide, cis-1,2-cyclohexanediamine, potassium carbonate and the substituted aniline of the structure shown in formula XIII into a Shrek tube, then introduce protective gas, and then add the seventh organic solvent to carry out the Ullmann reaction; the number of times the protective gas is introduced is preferably 3 times or more, more preferably 3 times; the protective gas is preferably N ₂ .

In the present invention, after the Ullmann reaction is completed, post-treatment is preferably performed; the post-treatment preferably includes: concentrating the mixed solution obtained by the Ullmann reaction, and then performing column chromatography on the obtained solid product to obtain an imidazopyridine-2-oxazoline compound with a structure shown in formula IV; the column chromatography device is preferably a silica gel chromatographic column, and the particle size of the silica gel is preferably 200 to 300 meshes.

The present invention also provides the use of the imidazopyridine-2-oxazoline compounds or their pesticide chemically acceptable salts described in the above scheme in the prevention and treatment of agricultural harmful pathogens.

In the present invention, the agricultural harmful pathogens preferably include one or more of Rhizoctonia solani, Rhizoctonia cerealis, Sclerotiniascleotiorum, Fusarium graminearum, Gaeumanomycegraminis, Botrytis cinerea, Phytophthora infestans, Phytophthora capsici, Alternaria solani, Fusarium fujikuroi, Fusarium sulphureum, Colletotrichum lagenarium and Pyricularia oryzac, and more preferably include Rhizoctonia solani. solani), Sclerotinia scleotiorum, Fusarium graminearum, Gaeumanomyce graminis, Botrytis cinerea and Phytophthora capsici.

In the present invention, the application preferably adopts the method of inhibiting the mycelium growth rate, indoor activity. The present invention has no special requirements for the method of inhibiting the mycelium growth rate, and conventional operations in the art can be adopted.

In order to further illustrate the present invention, the scheme of the present invention is described in detail below in conjunction with embodiments, but they should not be understood as limiting the scope of protection of the present invention.

Example 1

The synthesis reaction process of compound (s)-4-(tert-butyl)-2-(imidazo[1,2-a]pyridin-2-yl)-4,5-dihydrooxazole (Formula A1) is shown in the following formula:

(1) A solution of 2-aminopyridine (940 mg, 10 mmol) and ethyl 3-bromopyruvate (1505 μL, 12 mmol) in ethanol (25 mL) was stirred under reflux (metal bath) for 8 hours, and the solvent was evaporated under reduced pressure to 1 mbar. Then, a 15% sodium carbonate solution (15 mL) was added thereto to quench the reaction, and the mixture was extracted with dichloromethane (15 mL×3). The organic phases were combined, dried over anhydrous sodium sulfate, and separated by silica gel column chromatography (200-300 mesh, petroleum ether/ethyl acetate=1:1) to obtain intermediate A (ethyl imidazo[1,2-a]pyridine-2-carboxylate) as a light brown solid with a mass of 1365 mg and a yield of 72%;

(2) the imidazo[1,2-a]pyridine-2-carboxylic acid ethyl ester (1365 mg, 7.2 mmol) and 700 mg NaOH were refluxed in a mixture of methanol (25 mL) and water (36 mL) (metal bath), the resulting mixture was concentrated under vacuum (1 mbar) to remove the organic solvent, and the mixture was acidified with 1 mol/L HCl (pH 5-6), the solid was precipitated, filtered and dried at 50° C. for 5 hours to obtain intermediate B (imidazo[1,2-a]pyridine-2-carboxylic acid) as a yellow solid with a mass of 1030 mg and a yield of 88%;

(3) The imidazo[1,2-a]pyridine-2-carboxylic acid (162 mg, 1 mmol) was dissolved in anhydrous dichloromethane (5 mL), and a condensing agent 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 250 mg, 1.3 mmol) was added under ice bath conditions at 5°C, and stirred for 10 minutes. Subsequently, 1-hydroxybenzotriazole (HOBt, 178 mg, 1.3 mmol) was added, and then (s)-tert-leucine (144 mg, 1.2 mmol) was added. The reaction was stirred at room temperature for 24 hours, and the reaction was quenched with a 9.1 wt% saturated sodium bicarbonate solution. The mixture was extracted with dichloromethane (5 mL×2), and the solvent was evaporated under reduced pressure to 0.08 MPa. The intermediate C was separated by silica gel column chromatography (200-300 mesh, dichloromethane/ethyl acetate = 1:7) to obtain an intermediate C as a white solid with a mass of 123 mg and a yield of 47%;

(4) The intermediate C (261 mg, 1 mmol) was added to a Shrek tube, replaced with _N2 three times, and then dichloromethane (3 mL) was added to dissolve and transferred to -78°C. Diethylaminosulfur trifluoride (DAST, 368 μL, 3 mmol) was slowly added dropwise. After the addition was completed, the reaction was stirred at -78°C and monitored by TLC. After 8 hours, the reaction was complete. The reaction was quenched with water and washed with saturated sodium carbonate solution (10 mL×3). The organic phase was dried over anhydrous sodium sulfate, and the mixture was concentrated and separated by silica gel column chromatography (200-300 mesh, dichloromethane/ethyl acetate=1:4) to obtain (s)-4-(tert-butyl)-2-(imidazo[1,2-a]pyridin-2-yl)-4,5-dihydrooxazole (Formula A1) as a white solid with a mass of 158 mg and a yield of 65%. The hydrogen spectrum data and carbon spectrum data are as follows:

¹ H NMR (400 MHz, CDCl ₃ ) δ: 8.12-8.08 (m, 2H, hydrogen on the pyridine ring), 7.64 (dd, J=9.2, 1.0 Hz, 1H, hydrogen on the pyridine ring), 7.22-7.18 (m, 1H, hydrogen on the pyridine ring), 6.84-6.81 (m, 1H, hydrogen on the imidazole ring), 4.40 (dd, J=10.1, 8.5 Hz, 1H, hydrogen in OCH ₂ ), 4.26 (t, J=8.4 Hz, 1H, hydrogen in N-CH), 4.10 (dd, J=10.1, 8.2 Hz, 1H, hydrogen in OCH ₂ ), 0.97 (s, 9H, hydrogen in C(CH ₃ ) ₃ );

¹³ C NMR (101 MHz, CDCl ₃ ) δ: 159.45, 145.48, 134.71, 125.98, 125.65, 118.78, 114.21, 113.52, 76.53, 68.87, 34.06, 26.09.

Example 2

The synthesis reaction process of (4R,5R)-2-(imidazo[1,2-a]pyridin-2-yl)-4,5-diphenyl-4,5-dihydrooxazole (Formula A2) is shown in the following formula:

(1) Imidazolo[1,2-a]pyridine-2-carboxylic acid (162 mg, 1 mmol) was dissolved in anhydrous dichloromethane (5 mL). The condensing agent 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 250 mg, 1.3 mmol) was added under ice bath at 5°C. The mixture was stirred for 10 minutes. Subsequently, 1-hydroxybenzotriazole (HOBt, 178 mg, 1.3 mmol) was added. Then, (1S,2R)-2-amino-1,2-diphenylethanol (255 mg, 1.3 mmol) was added. g, 1.2 mmol), stirred at room temperature for 8 h, quenched with 9.1 wt% saturated sodium bicarbonate solution, extracted with dichloromethane (5 mL×2), reduced pressure to 0.05 MPa to evaporate the solvent, separated by silica gel column chromatography (200-300 mesh, dichloromethane/ethyl acetate=1:7), to obtain the intermediate N-((1R,2S)-2-hydroxy-1,2-diphenylethyl)imidazo[1,2-a]pyridine-2-carboxamide as a white solid with a mass of 178 mg and a yield of 50%;

(2) Add the N-((1R,2S)-2-hydroxy-1,2-diphenylethyl)imidazo[1,2-a]pyridine-2-carboxamide (1 mmol, 357 mg) into a Shrek tube and fill with N ₂ was replaced 3 times, then dichloromethane (3 mL) was added to dissolve and the mixture was transferred to -78 °C, diethylaminosulfur trifluoride (DAST, 368 μL, 3 mmol) was slowly added dropwise, and the reaction was stirred at -78 °C after the addition was completed. TLC tracking monitoring showed that the reaction was complete after 8 h, and the reaction was quenched with water and washed with 9.1 wt% saturated sodium carbonate solution (10 mL×3). The organic phase was dried over anhydrous sodium sulfate, and the mixture was concentrated and separated by silica gel column chromatography (200-300 mesh, dichloromethane/ethyl acetate=1:3) to obtain (4R,5R)-2-(imidazo[1,2-a]pyridin-2-yl)-4,5-diphenyl-4,5-dihydrooxazole (Formula A2) as a white solid with a mass of 261 mg and a yield of 77%. The hydrogen spectrum data and carbon spectrum data are as follows:

¹ H NMR (500 MHz, CDCl ₃ ) δ: 8.22 (s, 1H, hydrogen on the pyridine ring), 8.15 (d, J=7.2 Hz, 1H, hydrogen on the pyridine ring), 7.69 (d, J=9.0 Hz, 1H, hydrogen on the pyridine ring), 7.40-7.28 (m, 12H, hydrogen on the benzene ring), 7.23 (dd, J=7.2, 1.9 Hz, 1H, hydrogen on the pyridine ring), 6.86 (t, J=7.0 Hz, 1H, hydrogen on the imidazole ring), 5.46 (d, J=8.1 Hz, 1H, hydrogen in OCH ₂ ), 5.29 (d, J=7.9 Hz, 1H, hydrogen in N-CH);

¹³ C NMR (126MHz, CDCl ₃ ) δ: 160.32, 145.67, 141.83, 140.15, 134.27, 128.96, 128.90, 128.59, 127.85, 126.94, 126.15, 126.10, 125.92, 118.85, 114. 87, 113.73, 89.24, 78.93.

Example 3

The synthesis reaction process of (4R,5R)-2-(8-chloroimidazo[1,2-a]pyridin-2-yl)-4,5-diphenyl-4,5-dihydrooxazole A3 is shown in the following formula:

(1) 3-Bromoimidazo[1,2-a]pyridine-2-carboxylic acid (241 mg, 1 mmol) was dissolved in anhydrous dichloromethane (5 mL). The condensing agent 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 250 mg, 1.3 mmol) was added under ice bath at 2°C. The mixture was stirred for 10 minutes. Subsequently, 1-hydroxybenzotriazole (HOBt, 178 mg, 1.3 mmol) was added. Then, (1S,2R)-2-amino-1,2-diphenylethanol (255 mg, 1.3 mmol) was added. , 1.2mmol), stirred at room temperature for 24h, quenched with 9.1wt% saturated sodium bicarbonate solution, extracted with dichloromethane (5mL×2), reduced pressure to 0.08MPa to evaporate the solvent, separated by silica gel column chromatography (200-300mesh, dichloromethane/ethyl acetate=1:7), to obtain the intermediate 8-bromo-N-((1R,2S)-2-hydroxy-1,2-diphenylethyl)imidazo[1,2-a]pyridine-2-carboxamide as a white solid with a mass of 242mg and a yield of 56%;

(2) Add the 8-bromo-N-((1R,2S)-2-hydroxy-1,2-diphenylethyl)imidazo[1,2-a]pyridine-2-carboxamide (1 mmol, 436 mg) into a Shrek tube. ₂ was replaced 3 times, then dichloromethane (3 mL) was added to dissolve and the mixture was transferred to -78 °C, diethylaminosulfur trifluoride (DAST, 368 μL, 3 mmol) was slowly added dropwise, and the reaction was stirred at -78 °C after the addition was completed. TLC tracking and monitoring showed that the reaction was complete after 8 h, and the reaction was quenched with water and washed with saturated sodium carbonate solution (10 mL×3). The organic phase was dried over anhydrous sodium sulfate, and the mixture was concentrated and separated by silica gel column chromatography (200-300 mesh, dichloromethane/ethyl acetate=1:7) to obtain (4R,5R)-2-(8-bromoimidazo[1,2-a]pyridin-2-yl)-4,5-diphenyl-4,5-dihydrooxazole (Formula A3), which was a yellow oily liquid with a mass of 201 mg and a yield of 48%. The hydrogen spectrum data and carbon spectrum data were as follows:

¹ H NMR (500 MHz, CDCl ₃ ) δ: 8.23 (s, 1H, hydrogen on the pyridine ring), 8.04 (d, J=6.8 Hz, 1H, hydrogen on the pyridine ring), 7.38-7.23 (m, 11H, hydrogen on the benzene ring), 6.75 (dd, J=7.7, 6.5 Hz, 1H, hydrogen on the imidazole ring), 5.41 (d, J=8.0 Hz, 1H, hydrogen in OCH), 5.22 (d, J=7.8 Hz, 1H, hydrogen in N-CH);

¹³ C NMR (126MHz, CDCl ₃ ) δ: 171.31, 159.92, 143.21, 141.64, 140.01, 134.73, 128.95, 128.64, 128.90, 127.91, 126.96, 126.19, 124.88, 124.55, 116. 62, 113.39, 89.43, 78.97.

Example 4

The synthesis reaction process of (4R,5R)-2-(8-methylimidazo[1,2-a]pyridin-2-yl)-4,5-diphenyl-4,5-dihydrooxazole (Formula A4) is shown in the following formula:

(1) 3-Methylimidazo[1,2-a]pyridine-2-carboxylic acid (178 mg, 1 mmol) was dissolved in anhydrous dichloromethane (5 mL). The condensing agent 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 250 mg, 1.3 mmol) was added under ice bath at 0°C. The mixture was stirred for 10 minutes. Subsequently, 1-hydroxybenzotriazole (HOBt, 178 mg, 1.3 mmol) was added. Then, (1S,2R)-2-amino-1,2-diphenylethanol (255 mg, 1.3 mmol) was added. g, 1.2 mmol), stirred at room temperature for 12 h, quenched with 9.1 wt% saturated sodium bicarbonate solution, extracted with dichloromethane (5 mL×2), reduced pressure to 0.06 MPa to evaporate the solvent, separated by silica gel column chromatography (200-300 mesh, dichloromethane/ethyl acetate=1:7), to obtain the intermediate 8-methyl-N-((1R,2S)-2-hydroxy-1,2-diphenylethyl)imidazo[1,2-a]pyridine-2-carboxamide as a white solid with a mass of 195 mg and a yield of 53%;

(2) Add the 8-methyl-N-((1R,2S)-2-hydroxy-1,2-diphenylethyl)imidazo[1,2-a]pyridine-2-carboxamide (1 mmol, 371 mg) into a Shrek tube. ₂ was replaced 3 times, then dichloromethane (3 mL) was added to dissolve and the mixture was transferred to -78 °C, diethylaminosulfur trifluoride (DAST, 368 μL, 3 mmol) was slowly added dropwise, and the reaction was stirred at -78 °C after the addition was completed. TLC tracking and monitoring showed that the reaction was complete after 8 h, and the reaction was quenched with water and washed with saturated sodium carbonate solution (10 mL×3). The organic phase was dried over anhydrous sodium sulfate, and the mixture was concentrated and separated by silica gel column chromatography (200-300 mesh, dichloromethane/ethyl acetate=1:7) to obtain (4R,5R)-2-(8-methylimidazo[1,2-a]pyridin-2-yl)-4,5-diphenyl-4,5-dihydrooxazole (Formula A4), which was a colorless oily liquid with a mass of 164 mg and a yield of 44%. The hydrogen spectrum data and carbon spectrum data were as follows:

¹ H NMR (500 MHz, CDCl ₃ ) δ: 8.15 (d, J=7.1 Hz, 1H, hydrogen on the pyridine ring), 7.57 (d, J=8.8 Hz, 1H, hydrogen on the pyridine ring), 7.41-7.20 (m, 10H, hydrogen on the pyridine ring), 7.19-7.14 (m, 1H, hydrogen on the pyridine ring), 6.65 (d, J=6.9 Hz, 1H, hydrogen on the imidazole ring), 5.45 (d, J=7.8 Hz, 1H, hydrogen in OCH), 5.27 (d, J=7.9 Hz, 1H, hydrogen in N-CH), 2.55 (s, 3H, hydrogen in CH ₃ );

¹³ C NMR (126MHz, CDCl ₃ ) δ: 160.54, 146.15, 141.84, 140.13, 134.97, 134.14, 128.95, 128.90, 128.59, 127.85, 126.94, 126.15, 116.16, 112.70, 112. 31, 89.26, 78.92, 18.69.

Example 5

The synthesis reaction process of (4R,5R)-2-(8-methoxyimidazo[1,2-a]pyridin-2-yl)-4,5-diphenyl-4,5-dihydrooxazole A5 is shown in the following formula:

(1) 3-Methoxyimidazo[1,2-a]pyridine-2-carboxylic acid (178 mg, 1 mmol) was dissolved in anhydrous dichloromethane (5 mL). The condensing agent 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 250 mg, 1.3 mmol) was added under ice bath at 2°C. The mixture was stirred for 10 minutes. Subsequently, 1-hydroxybenzotriazole (HOBt, 178 mg, 1.3 mmol) was added. Then, (1S,2R)-2-amino-1,2-diphenylethanol (255 mg, 1.2mmol), stirred at room temperature for 20h, quenched with 9.1wt% saturated sodium bicarbonate solution, extracted with dichloromethane (5mL×2), reduced pressure to 0.07MPa to evaporate the solvent, separated by silica gel column chromatography (200-300mesh, dichloromethane/ethyl acetate=1:7), to obtain the intermediate 8-methoxy-N-((1R,2S)-2-hydroxy-1,2-diphenylethyl)imidazo[1,2-a]pyridine-2-carboxamide as a white solid with a mass of 278mg and a yield of 73.5%;

(2) Add the 8-methoxy-N-((1R,2S)-2-hydroxy-1,2-diphenylethyl)imidazo[1,2-a]pyridine-2-carboxamide (1 mmol, 387 mg) into a Shrek tube. ₂ was replaced 3 times, then dichloromethane (3 mL) was added to dissolve and the mixture was transferred to -78 °C, diethylaminosulfur trifluoride (DAST, 368 μL, 3 mmol) was slowly added dropwise, and the reaction was stirred at -78 °C after the addition was completed. TLC tracking and monitoring showed that the reaction was complete after 8 h, and the reaction was quenched with water and washed with saturated sodium carbonate solution (10 mL×3). The organic phase was dried over anhydrous sodium sulfate, and the mixture was concentrated and separated by silica gel column chromatography (200-300 mesh, dichloromethane/ethyl acetate=1:7) to obtain (4R,5R)-2-(8-methylimidazo[1,2-a]pyridin-2-yl)-4,5-diphenyl-4,5-dihydrooxazole (Formula A5) as a yellow solid with a mass of 258 mg and a yield of 70%. The hydrogen spectrum data and carbon spectrum data are as follows:

¹ HNMR (500 MHz, CDCl ₃ ) δ: 8.16 (s, 1H, hydrogen on the pyridine ring), 7.72 (dd, J=6.8, 0.9 Hz, 1H, hydrogen on the pyridine ring), 7.36-7.20 (m, 10H, hydrogen on the pyridine ring), 6.71 (dd, J=7.6, 6.8 Hz, 1H, hydrogen on the benzene ring), 6.43 (dd, J=7.7, 0.9 Hz, 1H, hydrogen on the imidazole ring), 5.40 (d, J=7.8 Hz, 1H, hydrogen in OCH 3 ), 5.21 (d, J=7.8 Hz, 1H, hydrogen in N-CH 3 ), 3.94 (s, 3H, hydrogen in OCH ₃ );

¹³ CNMR (126MHz, CDCl ₃ ) δ: 160.39, 149.75, 141.94, 140.32, 140.23, 133.50, 128.85, 128.82, 128.43, 127.79, 126.92, 126.08, 118.66, 115.85, 113. 75, 101.33, 89.09, 78.89, 55.86.

Example 6

The synthesis reaction process of (4R,5R)-4,5-diphenyl-2-(8-phenylimidazo[1,2-a]pyridin-2-yl)-4,5-dihydrooxazole A6 is shown in the following formula:

(1) 3-Bromoimidazo[1,2-a]pyridine-2-carboxylic acid (241 mg, 1 mmol) was dissolved in anhydrous dichloromethane (5 mL). The condensing agent 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 250 mg, 1.3 mmol) was added under ice bath at 2°C. The mixture was stirred for 10 minutes. Subsequently, 1-hydroxybenzotriazole (HOBt, 178 mg, 1.3 mmol) was added. Then, (1S,2R)-2-amino-1,2-diphenylethanol (255 mg, 1.3 mmol) was added. , 1.2mmol), stirred at room temperature for 24h, quenched with 9.1wt% saturated sodium bicarbonate solution, extracted with dichloromethane (5mL×2), reduced pressure to 0.08MPa to evaporate the solvent, separated by silica gel column chromatography (200-300mesh, dichloromethane/ethyl acetate=1:7), to obtain the intermediate 8-bromo-N-((1R,2S)-2-hydroxy-1,2-diphenylethyl)imidazo[1,2-a]pyridine-2-carboxamide as a white solid with a mass of 242mg and a yield of 56%;

(2) Add the 8-bromo-N-((1R,2S)-2-hydroxy-1,2-diphenylethyl)imidazo[1,2-a]pyridine-2-carboxamide (1 mmol, 436 mg) into a Shrek tube. ₂ was replaced 3 times, then dichloromethane (3 mL) was added to dissolve and the mixture was transferred to -78 °C, diethylaminosulfur trifluoride (DAST, 368 μL, 3 mmol) was slowly added dropwise, and the reaction was stirred at -78 °C. TLC tracking and monitoring showed that the reaction was complete after 8 h, and the reaction was quenched with water and washed with saturated sodium carbonate solution (10 mL × 3). The organic phase was dried over anhydrous sodium sulfate, and the mixture was concentrated and separated by silica gel column chromatography (200-300 mesh, dichloromethane/ethyl acetate = 1:7) to obtain (4R, 5R)-2-(8-bromoimidazo[1,2-a]pyridin-2-yl)-4,5-diphenyl-4,5-dihydrooxazole as a yellow oily liquid with a mass of 201 mg and a yield of 48%;

(3) The (4R,5R)-2-(8-bromoimidazo[1,2-a]pyridin-2-yl)-4,5-diphenyl-4,5-dihydrooxazole (83.4 mg, 0.2 mmol), phenylboric acid (48.4 mg, 0.4 mmol), tetrakis(triphenylphosphine)palladium (11.2 mg, 5 mol%) and potassium carbonate (54.4 mg, 0.4 eq) were dissolved in 1 mL of toluene and reacted at 100° C. for 24 h. The mixture was concentrated and separated by silica gel column chromatography (200-300 mesh, petroleum ether/ethyl acetate=5:1) to obtain (4R,5R)-4,5-diphenyl-2-(8-phenylimidazo[1,2-a]pyridin-2-yl)-4,5-dihydrooxazole (Formula A6) as a white solid with a mass of 17 mg and a yield of 20%. The hydrogen spectrum data and carbon spectrum data are as follows:

¹ HNMR (500 MHz, CDCl ₃ ) δ: 8.24 (d, J=1.3 Hz, 1H, hydrogen on benzene ring), 8.11-8.01 (m, 3H, hydrogen on benzene ring), 7.46-7.39 (m, 2H, hydrogen on benzene ring), 7.38-7.24 (m, 12H, hydrogen on pyridine ring and benzene ring), 6.90 (dd, J=6.9, 1.4 Hz, 1H, hydrogen on imidazole ring), 5.42 (d, J=8.4 Hz, 1H, hydrogen on OCH), 5.25 (d, J=8.2 Hz, 1H, hydrogen on N-CH);

¹³ CNMR (126MHz, CDCl ₃ ) δ: 160.44, 144.69, 141.84, 140.29, 135.97, 134.30, 131.54, 127.84, 127.06, 126.18, 125.01, 124.14, 115.89, 113.88, 89.15, 79.14.

Example 7

The synthesis reaction process of (4R,5R)-2-(8-phenoxyimidazo[1,2-a]pyridin-2-yl)-4,5-diphenyl-4,5-dihydrooxazole A7 is shown in the following formula:

(1) 3-Bromoimidazo[1,2-a]pyridine-2-carboxylic acid (241 mg, 1 mmol) was dissolved in anhydrous dichloromethane (5 mL). The condensing agent 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 250 mg, 1.3 mmol) was added under ice bath at 2°C. The mixture was stirred for 10 minutes. Subsequently, 1-hydroxybenzotriazole (HOBt, 178 mg, 1.3 mmol) was added. Then, (1S,2R)-2-amino-1,2-diphenylethanol (255 mg, 1.3 mmol) was added. , 1.2mmol), stirred at room temperature for 24h, quenched with 9.1wt% saturated sodium bicarbonate solution, extracted with dichloromethane (5mL×2), reduced pressure to 0.08MPa to evaporate the solvent, separated by silica gel column chromatography (200-300mesh, dichloromethane/ethyl acetate=1:7), to obtain the intermediate 8-bromo-N-((1R,2S)-2-hydroxy-1,2-diphenylethyl)imidazo[1,2-a]pyridine-2-carboxamide as a white solid with a mass of 242mg and a yield of 56%;

(2) Add the 8-bromo-N-((1R,2S)-2-hydroxy-1,2-diphenylethyl)imidazo[1,2-a]pyridine-2-carboxamide (1 mmol, 436 mg) into a Shrek tube. ₂ was replaced 3 times, then dichloromethane (3 mL) was added to dissolve and the mixture was transferred to -78°C, diethylaminosulfur trifluoride (DAST, 368 μL, 3 mmol) was slowly added dropwise, and the reaction was stirred at -78°C. TLC tracking and monitoring showed that the reaction was complete after 8 h, and the reaction was quenched with water and washed with saturated sodium carbonate solution (10 mL×3). The organic phase was dried over anhydrous sodium sulfate, and the mixture was concentrated and separated by silica gel column chromatography (200-300 mesh, dichloromethane/ethyl acetate=1:7) to obtain (4R,5R)-2-(8-bromoimidazo[1,2-a]pyridin-2-yl)-4,5-diphenyl-4,5-dihydrooxazole as a yellow oily liquid with a mass of 201 mg and a yield of 48%;

(3) The (4R,5R)-2-(8-bromoimidazo[1,2-a]pyridin-2-yl)-4,5-diphenyl-4,5-dihydrooxazole (83.4 mg, 0.2 mmol), cuprous iodide (11.4 mg, 0.06 mmol), N,N-dimethylglycine (DMG, 6.2 mg, 0.06 mmol), cesium carbonate (84.8 mg, 0.4 mmol) and phenol (28.2 mg, 0.3 mmol) were added to a Shrek tube. ₂ was replaced 3 times, then 1 mL of dioxane was added, and the mixture was reacted at 105°C for 24 h. The mixture was concentrated and separated by silica gel column chromatography (200-300 mesh, petroleum ether/ethyl acetate = 5:1) to obtain (4R, 5R)-2-(8-phenoxyimidazo[1,2-a]pyridin-2-yl)-4,5-diphenyl-4,5-dihydrooxazole (Formula A7) as a yellow solid with a mass of 13 mg and a yield of 15%. The hydrogen spectrum data and carbon spectrum data are as follows:

¹ H NMR (400 MHz, CDCl ₃ ) δ: 8.29 (d, J=6.7 Hz, 1H, hydrogen on the pyridine ring), 7.87 (dd, J=6.8, 0.9 Hz, 1H, hydrogen on the pyridine ring), 7.56-7.26 (m, 12H, hydrogen on the pyridine ring and benzene ring), 7.27-7.16 (m, 3H, hydrogen on the benzene ring), 6.81-6.66 (m, 1H), 6.42 (dd, J=7.7, 0.9 Hz, 1H, hydrogen on the imidazole ring), 5.47 (d, J=7.9 Hz, 1H, hydrogen in OCH), 5.29 (d, J=7.9 Hz, 1H, hydrogen in N-CH);

¹³ C NMR (101MHz, CDCl ₃ ) δ: 160.31, 154.75, 148.88, 141.85, 140.14, 134.07, 130.11, 128.92, 128.58, 127.88, 126.99, 126.25, 125.21, 121.00, 120. 08, 116.09, 113.53, 106.89, 89.34, 78.93 .

Example 8

The synthesis reaction process of 2-((4R, 5R)-4,5-diphenyl-4,5-dihydrooxazol-2-yl)-N-phenylimidazo[1,2-a]pyridine-8-amine (Formula A8) is shown in the following formula:

(1) 3-Bromoimidazo[1,2-a]pyridine-2-carboxylic acid (241 mg, 1 mmol) was dissolved in anhydrous dichloromethane (5 mL). The condensing agent 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 250 mg, 1.3 mmol) was added under ice bath at 2°C. The mixture was stirred for 10 minutes. Subsequently, 1-hydroxybenzotriazole (HOBt, 178 mg, 1.3 mmol) was added. Then, (1S,2R)-2-amino-1,2-diphenylethanol (255 mg, 1.3 mmol) was added. , 1.2mmol), stirred at room temperature for 24h, quenched with 9.1wt% saturated sodium bicarbonate solution, extracted with dichloromethane (5mL×2), reduced pressure to 0.08MPa to evaporate the solvent, separated by silica gel column chromatography (200-300mesh, dichloromethane/ethyl acetate=1:7), to obtain the intermediate 8-bromo-N-((1R,2S)-2-hydroxy-1,2-diphenylethyl)imidazo[1,2-a]pyridine-2-carboxamide as a white solid with a mass of 242mg and a yield of 56%;

(2) The intermediate 8-bromo-N-((1R,2S)-2-hydroxy-1,2-diphenylethyl)imidazo[1,2-a]pyridine-2-carboxamide (1 mmol, 436 mg) was added to a Shrek tube. ₂ was replaced 3 times, then dichloromethane (3 mL) was added to dissolve and the mixture was transferred to -78 °C, diethylaminosulfur trifluoride (DAST, 368 μL, 3 mmol) was slowly added dropwise, and the reaction was stirred at -78 °C. TLC tracking and monitoring showed that the reaction was complete after 8 h, and the reaction was quenched with water and washed with saturated sodium carbonate solution (10 mL × 3). The organic phase was dried over anhydrous sodium sulfate, and the mixture was concentrated and separated by silica gel column chromatography (200-300 mesh, dichloromethane/ethyl acetate = 1:7) to obtain (4R, 5R)-2-(8-bromoimidazo[1,2-a]pyridin-2-yl)-4,5-diphenyl-4,5-dihydrooxazole as a yellow oily liquid with a mass of 201 mg and a yield of 48%;

(3) The (4R,5R)-2-(8-bromoimidazo[1,2-a]pyridin-2-yl)-4,5-diphenyl-4,5-dihydrooxazole (83.4 mg, 0.2 mmol), aniline (28 mg, 0.3 mmol), cuprous iodide and cis-1,2-cyclohexanediamine were added to a Shrek tube, and _N2 was replaced three times. Then, 1 mL of dioxane was added, and the mixture was reacted at 110°C for 24 h. The mixture was concentrated and separated by silica gel column chromatography (200-300 mesh, petroleum ether/ethyl acetate = 5:1) to obtain 2-((4R,5R)-4,5-diphenyl-4,5-dihydrooxazol-2-yl)-N-phenylimidazo[1,2-a]pyridin-8-amine (Formula A8) as a yellow solid with a mass of 13 mg and a yield of 15%. The hydrogen spectrum data and carbon spectrum data are as follows:

¹ H NMR (400 MHz, CDCl ₃ ) δ: 8.18 (s, 1H, hydrogen on pyridine ring), 8.10-7.90 (m, 5H, hydrogen on benzene ring), 7.52-7.10 (m, 12H, hydrogen on pyridine ring and benzene ring), 6.87 (d, J=6.9 Hz, 1H, hydrogen on imidazole ring), 5.37 (d, J=8.6 Hz, 1H, hydrogen in OCH), 5.22 (d, J=7.9 Hz, 1H, hydrogen in N-CH);

¹³ C NMR (126MHz, CDCl ₃ ) δ: 160.29, 141.80, 140.52, 140.42, 140.24, 133.71, 132.52, 129.54, 128.96, 128.66, 127.87, 126.99, 126.11, 123.04, 120. 54, 116.38, 116.04, 114.84, 100.46, 89.34 .

Example 9

The synthesis reaction process of (R)-2-(8-bromoimidazo[1,2-a]pyridin-2-yl)-5-phenyl-4,5-dihydrooxazole (Formula A9) is shown in the following formula:

(1) 3-Bromoimidazo[1,2-a]pyridine-2-carboxylic acid (241 mg, 1 mmol) was dissolved in anhydrous dichloromethane (5 mL). The condensing agent 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 250 mg, 1.3 mmol) was added under ice-bath at 3°C. The mixture was stirred for 10 minutes. Subsequently, 1-hydroxybenzotriazole (HOBt, 178 mg, 1.3 mmol) was added. Then, (S)(S)-2-amino-1-phenylethane-1-ol (16 4 mg, 1.2 mmol), stirred at room temperature for 24 h, quenched with 9.1 wt% saturated sodium bicarbonate solution, extracted with dichloromethane (5 mL × 2), reduced pressure to 0.07 MPa to evaporate the solvent, separated by silica gel column chromatography (200-300 mesh, dichloromethane/ethyl acetate = 1:7), to obtain the intermediate (S)-8-bromo-N-(2-hydroxy-2-phenylethyl)imidazo[1,2-a]pyridine-2-carboxamide as a white solid with a mass of 100 mg and a yield of 28%;

(2) The intermediate (S)-8-bromo-N-(2-hydroxy-2-phenylethyl)imidazo[1,2-a]pyridine-2-carboxamide (1 mmol, 359 mg) was added to a Shrek tube. ₂ was replaced 3 times, then dichloromethane (3 mL) was added to dissolve and the mixture was transferred to -78 °C, diethylaminosulfur trifluoride (DAST, 368 μL, 3 mmol) was slowly added dropwise, and the reaction was stirred at -78 °C after the addition was completed. TLC tracking and monitoring showed that the reaction was complete after 8 h, and the reaction was quenched with water and washed with saturated sodium carbonate solution (10 mL×3). The organic phase was dried over anhydrous sodium sulfate, and the mixture was concentrated and separated by silica gel column chromatography (200-300 mesh, dichloromethane/ethyl acetate=1:7) to obtain (R)-2-(8-bromoimidazo[1,2-a]pyridin-2-yl)-5-phenyl-4,5-dihydrooxazole (Formula A9) as a white solid with a mass of 123 mg and a yield of 36%. The hydrogen spectrum data and carbon spectrum data are as follows:

¹ H NMR (500 MHz, CDCl ₃ ) δ8.25 (s, 1H, hydrogen on pyridine ring), 8.10 (dd, J=6.8, 1.0 Hz, 1H, hydrogen on pyridine ring), 7.48 (dd, J=7.3, 1.0 Hz, 1H, hydrogen on pyridine ring), 7.35-7.23 (m, 5H, hydrogen on benzene ring), 6.76-6.67 (m, 1H, hydrogen on imidazole ring), 5.39 (dd, J=10.2, 8.4 Hz, 1H, hydrogen in N-CH), 4.83 (dd, J=10.2, 8.5 Hz, 1H, hydrogen in N-CH), 4.33 (t, J=8.4 Hz, 1H, hydrogen in OCH).

¹³ C NMR (126MHz, CDCl ₃ ) δ: 160.49, 143.55, 142.02, 134.77, 128.80, 128.31, 127.74, 126.91, 125.36, 113.75, 112.60, 74.97, 70.26.

Example 10

The synthesis reaction process of (S)-4-(tert-butyl)-2-(7-methylimidazo[1,2-a]pyridin-2-yl)-4,5-dihydrooxazole (Formula A10) is shown in the following formula:

(1) 4-Methylimidazo[1,2-a]pyridine-2-carboxylic acid (178 mg, 1 mmol) was dissolved in anhydrous dichloromethane (5 mL). The condensing agent 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 250 mg, 1.3 mmol) was added under ice bath at 0°C. The mixture was stirred for 10 minutes. Then 1-hydroxybenzotriazole (HOBt, 178 mg, 1.3 mmol) and (s)-tert-leucine (144 mg, 1.2 mmol) were added. ), stirred at room temperature for 8 h, quenched with 9.1 wt% saturated sodium bicarbonate solution, extracted with dichloromethane (5 mL×2), reduced pressure to 0.05 MPa to evaporate the solvent, separated by silica gel column chromatography (200-300 mesh, dichloromethane/ethyl acetate=1:7), to obtain the intermediate (S)-N-(1-hydroxy-3,3-dimethylbutan-2-yl)-7-methylimidazo[1,2-a]pyridine-2-carboxamide as a white solid with a mass of 210 mg and a yield of 76%;

(2) Add the (S)-N-(1-hydroxy-3,3-dimethylbutan-2-yl)-7-methylimidazo[1,2-a]pyridine-2-carboxamide (1 mmol, 275 mg) into a Shrek tube. ₂ was replaced 3 times, then dichloromethane (3 mL) was added to dissolve and the mixture was transferred to -78 °C, diethylaminosulfur trifluoride (DAST, 368 μL, 3 mmol) was slowly added dropwise, and the reaction was stirred at -78 °C after the addition was completed. TLC tracking and monitoring showed that the reaction was complete after 8 h, and the reaction was quenched with water and washed with saturated sodium carbonate solution (10 mL×3). The organic phase was dried over anhydrous sodium sulfate, and the mixture was concentrated and separated by silica gel column chromatography (200-300 mesh, dichloromethane/ethyl acetate=1:7) to obtain (S)-4-(tert-butyl)-2-(7-methylimidazo[1,2-a]pyridin-2-yl)-4,5-dihydrooxazole (Formula A10) as a yellow solid with a mass of 179 mg and a yield of 70%. The hydrogen spectrum data and carbon spectrum data are as follows:

¹ H NMR (500 MHz, CDCl ₃ ) δ8.04 (d, J=4.9 Hz, 1H, hydrogen on pyridine ring), 7.87 (s, 1H, hydrogen on pyridine ring), 7.55 (d, J=9.3 Hz, 1H, hydrogen on pyridine ring), 7.04 (dd, J=9.4, 1.8 Hz, 1H, hydrogen on imidazole ring), 4.38 (dd, J=10.2, 8.6 Hz, 1H, hydrogen in N-CH), 4.25 (t, J=8.3 Hz, 1H, hydrogen in OCH), 4.08 (dd, J=10.2, 8.0 Hz, 1H, hydrogen in N-CH), 2.30 (s, 3H, -CH ₃ ), 0.95 (s, 9H, -C(CH ₃ ) ₃ ).

¹³ CNMR (126MHz, CDCl ₃ ) δ: 160.54, 146.15, 141.84, 140.13, 134.97, 134.14, 128.95, 128.90, 128.59, 127.85, 126.94, 126.15, 116.16, 112.70, 112. 31, 89.26, 78.92, 18.51.

The in vitro antibacterial activity of the imidazoheterocyclic-2-oxazoline compounds prepared in Examples 1 to 10 was detected by the method of inhibiting mycelial growth rate. The detection method is as follows: the test strains of rice sheath blight, rapeseed sclerotinia, wheat fusarium, tomato gray mold and pepper phytophthora were selected and activated on a PDA plate, and the imidazoheterocyclic-2-oxazoline compounds of Examples 1 to 10 were respectively configured into a series of gradient concentrations (100 μmol, 50 μmol, 25 μmol, 12.5 μmol, 6.25 μmol, 10 μmol, 25 μmol, 30 μmol, 15 μmol, 20 μmol, 30 μmol, 40 μmol, 50 ...30 μmol, 40 μmol, 50 μmol, 30 μmol, 40 μmol, 50 μmol, 30 μmol, 40 μmol, 50 μmol, 30 μmol, 40 μmol, 50 μmol, 30 μmol, 40 μmol, 50 μmol, 30 μmol, mol, 3.13 μmol, 1.56 μmol and 0.78 μmol) of PDA drug-containing plates, the above test strains were made into 5 mm diameter bacterial cakes, respectively placed in the center of the PDA drug-containing plates with different concentrations, and cultured at 25°C until the test strains in the blank control dishes grew close to the edge of the culture dishes, and the colony diameters of each PDA drug-containing plate were measured by the cross method, and the inhibition rate of the imidazoheterocyclic-2-oxazoline compounds of Examples 1 to 10 on mycelial growth was calculated, and the inhibition rate was calculated according to the following formula:

The statistical software SPSS 26.0 was used to calculate the concentration of the imidazoheterocyclic-2-oxazoline compounds of Examples 1 to 9 when the inhibition rate was 50%, i.e., the EC50 value. The calculation was repeated 3 times and the average value was taken to obtain the final result. Boscalid and thiabendazole were used as positive controls in the test. The results are shown in Tables 1 and 2.

Table 1 Inhibition rate of five agricultural fungi in Examples 1 to 10 and the positive control

According to Table 1, the imidazopyridine-2-oxazoline compounds obtained in the examples of the present invention have a certain inhibitory effect on a variety of plant pathogens, and the type of oxazoline fragment and the type of substituent on the pyridine ring have a significant effect on the antibacterial activity: when the substituent introduced on the pyridine is methyl, the antibacterial activity of the imidazopyridine-2-oxazoline compounds is significantly improved; when two phenyl substituents are introduced on the oxazoline ring, the antibacterial activity and antibacterial spectrum of the imidazopyridine-2-oxazoline compounds are significantly improved.

Table 2 The inhibition concentration EC50 of Examples 1 to 9 and the positive control on five agricultural fungi

According to Table 2, after structural optimization, when there is no group substitution on the pyridine ring and two phenyl groups are substituted on the oxazoline ring, the EC50 values of the imidazopyridine-2-oxazoline compounds of the present invention against rice sheath blight, rapeseed sclerotinia, tomato gray mold, and wheat fusarium are 1.9 μmol/L, 89.3 μmol/L, 44.3 μmol/L, and 23.4 μmol/L, respectively, and the activity against rice sheath blight and wheat fusarium is significantly higher than that of the positive controls boscalid and thiabendazole. It can be seen that the imidazopyridine-2-oxazoline compounds provided by the present invention are expected to be used as a new type of fungicide candidate compound or directly as a fungicide.

It can be seen from the above examples that the imidazopyridine-2-oxazoline compounds provided by the present invention have a strong active inhibitory effect on a variety of agricultural harmful pathogens, and are particularly suitable for plant fungal diseases. In addition, the imidazopyridine-2-oxazoline compounds provided by the present invention basically do not cause drug resistance in agricultural harmful pathogens, are environmentally friendly, green and environmentally friendly, and have positive significance for the creation of new pesticides.

Although the above embodiment describes the present invention in detail, it is only a part of the embodiments of the present invention, not all of the embodiments. Other embodiments can be obtained based on this embodiment without creativity, and these embodiments all fall within the protection scope of the present invention.

Claims (10)

1. An imidazopyridine-2-oxazoline compound or a pesticide chemically acceptable salt thereof, the structure of the imidazopyridine-2-oxazoline compound is as shown in Formula I: Formula I; In the formula I, the configuration of the carbon center substituted by R ₁ and R ₂ is independently R type or S type; The R ₁ is a C ₁ to C ₈ hydrocarbon group; The R ₂ is C ₁ ~ C ₄ alkyl or phenyl; The R ₃ is hydrogen, halogen, C ₁ ~ C ₆ alkyl, C ₁ ~ C ₆ alkoxy, phenyl, substituted phenyl, phenoxy, substituted phenoxy, phenylamino, substituted phenyl Amino; the substituent of the substituted phenyl group is C ₁ ~ C ₆ hydrocarbyl group; the substituent of the substituted phenoxy group is C ₁ ~ C ₆ hydrocarbyl group; the substituent of the substituted phenylamino group is C ₁ ~ C ₆ hydrocarbyl. 2. The imidazopyridine-2-oxazoline compound according to claim 1, wherein R ₁ is phenyl. 3. An imidazopyridine-2-oxazoline compound, characterized in that its structural formula is one of formulas A2 to A9: . 4. The preparation method of imidazopyridine-2-oxazoline compounds according to any one of claims 1 to 3, comprising the following steps: (1) Mix substituted 2-aminopyridine, pyruvate and the first organic solvent for reflux reaction to obtain intermediate A; the structure of the substituted 2-aminopyridine is shown in formula V, and the structure of intermediate A is As shown in Formula VI: Formula V; Formula VI; (2) Mix the intermediate A, the alkali metal hydroxide and the second organic solvent to perform a hydrolysis reaction to obtain the intermediate B; the structure of the intermediate B is shown in Formula VII: Formula VII; (3) Mix the intermediate B, condensation agent, 1-hydroxybenzotriazole, chiral aminoalcohol and a third organic solvent to perform a condensation reaction to obtain intermediate C; the structure of the chiral aminoalcohol is as follows: Formula VIII As shown, the structure of the intermediate C is shown in formula IX: Formula VIII; Formula IX; (4) Mix the intermediate C, diethylaminosulfur trifluoride and the fourth organic solvent to perform a ring-forming reaction to obtain the imidazopyridine-2-oxazoline compound with the structure shown in formula I. 5. The imidazopyridine-2-oxazoline compound of claim 1, when the R ₃ is a substituted phenyl group, and the substituent of the substituted phenyl group is a C ₁ to C ₆ hydrocarbon group, the The preparation method of imidazopyridine-2-oxazoline compounds includes the following steps: Mix the compound with the structure represented by formula Oxazoline compounds: Formula X; Formula XI. 6. The imidazopyridine-2-oxazoline compound of claim 1, when the R ₃ is a phenoxy group or a substituted phenoxy group, the substituent of the substituted phenoxy group is C ₁ ~C When ₆ hydrocarbyl groups are used, the preparation method of the imidazopyridine-2-oxazoline compound includes the following steps: Mix the compound with the structure shown in Formula -2-oxazoline compounds: Formula XII; Formula X. 7. The imidazopyridine-2-oxazoline compound of claim 1, when the R ₃ is an phenylamino group or a substituted phenylamino group, and the substituent of the substituted phenylamino group is a C ₁ to C ₆ hydrocarbyl group , the preparation method of the imidazopyridine-2-oxazoline compound includes the following steps: Mix the compound with the structure shown in Formula X, copper iodide, cis-1,2-cyclohexanediamine, potassium carbonate, the substituted aniline with the structure shown in Formula Pyridine-2-oxazoline compounds: Formula XIII; Formula X. 8. The preparation method according to claim 4, characterized in that the molar ratio of substituted 2-aminopyridine and pyruvate in step (1) is 1:1.5~3; the intermediate in step (3) The molar ratio of body B and chiral aminoalcohol is 1:1~3; the molar ratio of intermediate B and condensing agent is 1:1.2~3; the molar ratio of intermediate B and 1-hydroxybenzotriazole The ratio is 1:1.2~5; the molar ratio of intermediate C and diethylaminosulfur trifluoride described in step (4) is 1:3~6. 9. The preparation method according to claim 4, characterized in that the temperature of the reflux reaction in step (1) is 30~100°C and the time is 6~24 h; the hydrolysis reaction in step (2) is The temperature is 0~80 ℃, and the time is 6~72 h; the temperature of the condensation reaction described in step (3) is 0~40 ℃, and the time is 12~96 h; the temperature of the cyclization reaction described in step (4) is -5~25℃, time is 0.5~14 h. 10. Application of the imidazopyridine-2-oxazoline compound or its pesticide chemically acceptable salt according to any one of claims 1 to 3 in the prevention and control of harmful agricultural pathogens.