Pyrimidine-containing benzopyrone compound as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of agricultural bactericidal, insecticidal and acaricidal compounds, and discloses a pyrimidine-containing benzopyrone compound of which the structural general formula is as shown in formula I, the compound has broad-spectrum bactericidal activity, has an excellent prevention and treatment effect on cucumber downy mildew, shows very good insecticidal activity, and has a relatively high fatality rate on plutella xylostella and armyworm.

Description

Technical Field

[0001] The invention belongs to the technical field of agricultural bactericidal, insecticidal and acaricidal compounds, and relates to a pyrimidine-containing benzopyrone compound and a preparation method and application thereof. Background Art

[0002] Benzopyrone (i.e., coumarin) compounds are a class of natural products with excellent anti-cancer, anti-HIV, anti-malarial, antioxidant and antibacterial activities. However, their application in the field of pesticides is still relatively rare, and there are only two commercial varieties at present. For example, a methoxyacrylate fungicide syringoxystrobin (CN 1310899C) developed by Shenyang Chemical Research Institute has excellent preventive effects on apple brown spot disease and wheat stripe blight; and an organophosphorus insecticide cypermethrin (Soap Sanitary Chem., 1954, 30, 159.) first developed by Bayer in Germany in the 1950s is particularly effective against dipteran pests and can also be used to control external parasites and skin flies.

[0003]

[0004] Pyrimidine compounds are an important class of fungicides developed since the 1950s. They are effective against various diseases caused by Botrytis cinerea. They act as mitochondrial complex I electron transfer inhibitors and are one of the few fungicides for which resistance has not yet been reported. They also have no cross-resistance with common fungicides. These properties indicate that pyrimidines are a class of potential compounds for the discovery of pesticide candidate varieties. For example, diflumetorim, which was approved for registration in Japan in 1997, has excellent control effects on wheat powdery mildew and rust (EP 0370704); and cyprodinil, a fungicide developed by Syngenta, has good control effects on gray mold, powdery mildew and black spot (EP 310550).

[0005]

[0006] Therefore, in order to continue to search for compounds with excellent biological activity from benzopyrone derivatives, we adopted the principle of active substructure splicing, rationally combined the substituted pyrimidine group with the benzopyrone skeleton, and disclosed a class of pyrimidine-containing benzopyrone compounds with good fungicidal and insecticidal activities. Summary of the invention

[0007] The present invention aims at the technical problem that there are few types of benzopyrone derivatives used in the agricultural field, provides a pyrimidine-containing benzopyrone compound and a preparation method and application thereof, and achieves good bactericidal and insecticidal activities.

[0008] To achieve the above object, the present invention adopts the following technical solutions:

[0009] In a first aspect, the present invention provides a pyrimidine-containing benzopyrone compound, the general structural formula of which is shown in Formula I:

[0010]

[0011] Where: Q is

[0012] R1 is selected from hydrogen, halogen, cyano, nitro, amino, carboxyl, C1-C4 alkyl, halogenated C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 alkoxy or halogenated C1-C4 alkoxy;

[0013] R2 is selected from hydrogen, halogen, cyano, nitro, amino, carboxyl, formyl, C1-C4 alkyl, halogenated C1-C4 alkyl or C1-C4 alkoxy;

[0014] W is selected from hydrogen, halogen, C1-C4 alkyl, halogenated C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 alkoxy, C1-C4 alkylthio or C1-C4 alkylsulfonyl;

[0015] R3 is selected from hydrogen, hydroxy, formyl, C1-C4 alkyl, halogenated C1-C4 alkyl, C1-C4 alkoxy, halogenated C1-C4 alkoxy, C3-C4 cycloalkyl, C1-C4 alkylthio, C2-C4 alkenylthio, C2-C4 alkenyl or C2-C4 alkynyl;

[0016] R4 and R5 are identically or differently selected from hydrogen, halogen, cyano, nitro, C1-C4 alkyl, halogenated C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 alkoxy or halogenated C1-C4 alkoxy;

[0017] R6 is selected from hydrogen, halogen, C1-C4 alkyl;

[0018] R7 is selected from hydrogen, halogen, carboxyl, C1-C4 alkyl, C1-C4 alkoxy;

[0019] R8 is selected from hydrogen, halogen, nitro, C1-C4 alkyl, C1-C4 alkoxy;

[0020] R9 is selected from hydrogen, halogen;

[0021] The connection position of O to the benzopyrone ring is selected from the 4-position or the 7-position.

[0022] Preferably, in the general structural formula I:

[0023] R1 is selected from methyl, ethyl, chloro or difluoromethyl;

[0024] R2 is selected from hydrogen, methyl or chlorine;

[0025] W is selected from hydrogen or methyl;

[0026] R3 is selected from hydrogen;

[0027] R4 is selected from hydrogen or methyl;

[0028] R5 is selected from hydrogen or n-butyl;

[0029] R6, R8, and R9 are all selected from hydrogen;

[0030] R7 is selected from hydrogen or chlorine;

[0031] The connection position of O to the benzopyrone ring is selected from the 4-position or the 7-position.

[0032] In the above terms, halogen: refers to fluorine, chlorine, bromine or iodine. Nitro: -NO2. Cyano: -CN. Tertiary amine cation -NR3. Sulfonic acid group -SO3H. Trihalomethyl: -CX3, X = F, Cl. Formyl: -CHO. Acyl: -CO-alkoxy. Carboxyl: -COOH. Alkyl: straight chain or branched chain alkyl, such as methyl, ethyl, propyl, isopropyl, n-butyl or tert-butyl. Cycloalkyl: substituted or unsubstituted cyclic alkyl, such as cyclopropyl, cyclopentyl or cyclohexyl. Haloalkyl: straight chain or branched chain alkyl, hydrogen atoms on these alkyl may be partially or completely replaced by halogen atoms, such as chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, etc. Alkylsulfinyl: straight chain or branched chain alkyl is connected to the structure via a sulfinyl group (-SO-), such as methylsulfinyl. Haloalkylsulfinyl: a straight or branched alkylsulfinyl group, in which the hydrogen atoms on the alkyl group may be partially or completely replaced by halogen atoms. The aryl part in (hetero)aryl, (hetero)arylalkyl, (hetero)arylcarbonyl, (hetero)arylmethylcarbonyl, (hetero)arylcarbonylalkyl, (hetero)aryloxycarbonyl, (hetero)arylalkyloxycarbonyl includes phenyl or naphthyl. Heteroaryl is a five-membered ring or six-membered ring containing one or more N heteroatoms, such as pyridyl, pyrimidinyl, pyrazinone, pyridazinyl, triazinyl, etc. (hetero)aryl: such as phenyl, etc.

[0033] Tables 1 and 2 respectively list some specific substituents of R3 and R4 (R5) in the general structural formula I, but they are not limited to these substituents.

[0034] Table 1 R3 Substituents

[0035] <![CDATA[R3]]> <![CDATA[R3]]> <![CDATA[R3]]> <![CDATA[R3]]> H OH -C(=O)H <![CDATA[CBr3]]> <![CDATA[CH3]]> <![CDATA[C2H5]]> <![CDATA[n-C3H7]]> <![CDATA[i-C3H7]]> <![CDATA[n-C4H9]]> <![CDATA[i-C4H9]]> <![CDATA[t-C4H9]]> <![CDATA[CCl3]]> <![CDATA[CH2Br]]> <![CDATA[CHF2]]> <![CDATA[CHBr2]]> <![CDATA[CF3]]> <![CDATA[CH2Cl]]> <![CDATA[CHCl2]]> <![CDATA[CCl3]]> <![CDATA[CH2F]]> <![CDATA[OCH3]]> <![CDATA[OC2H5]]> <![CDATA[OCH(CH3)2]]> <![CDATA[OC(CH3)3]]> <![CDATA[OCF3]]> <![CDATA[OCH2CF3]]> <![CDATA[OCH2F]]> <![CDATA[OCHF2]]>

[0036] Table 2 R4 (R5) Substituents

[0037]

[0038]

[0039] In the above structural formula I, when O is connected to the 7-position of the benzopyrone ring and R3=R4=R5=H, the structure of the pyrimidine part R in the compound is different. The substituents R1, R2, R6~R9, W of the pyrimidine part are shown in Table 3, and the compound numbers are 3-1 to 3-67.

[0040] Table 3 Pyrimidine partial substituents

[0041]

[0042]

[0043]

[0044] In the above general structural formula I, when O is connected to the 7-position of the benzopyrone ring, and R3=R5=H, R4=CH3, the substituents R1, R2, R6~R9, W are consistent with Table 3, corresponding to 3-1 to 3-67 in Table 3, and the representative compound numbers are 4-1 to 4-67, respectively.

[0045] In the above structural formula I, in formula I, when O is connected to the 7-position of the benzopyrone ring, and R3=H, R4=CH3, R5=n-C4H9, the substituents R1, R2, R6-R9, and W are consistent with Table 3, corresponding to 3-1 to 3-67 in Table 3, and the representative compound numbers are 5-1 to 5-67, respectively.

[0046] In the above general structural formula I, when O is connected to the 7-position of the benzopyrone ring, and R3=CH3, R4=R5=H, the substituents R1, R2, R6-R9, and W are consistent with Table 3, corresponding to 3-1 to 3-67 in Table 3, and the representative compound numbers are 6-1 to 6-67, respectively.

[0047] In the above general structural formula I, when O is connected to the 7-position of the benzopyrone ring, and R3=R4=CH3, R5=H, the substituents R1, R2, R6-R9, and W are consistent with Table 3, corresponding to 3-1 to 3-67 in Table 3, and the representative compound numbers are 7-1 to 7-67, respectively.

[0048] In the above general structural formula I, when O is connected to the 7-position of the benzopyrone ring, and R3=R4=CH3, R5=n-C4H9, the substituents R1, R2, R6-R9, and W are consistent with Table 3, corresponding to 3-1 to 3-67 in Table 3, and the representative compound numbers are 8-1 to 8-67, respectively.

[0049] In the above general structural formula I, when O is connected to the 4-position of the benzopyrone ring and R3=R5=H, the substituents R1, R2, R6-R9, and W are consistent with Table 3, corresponding to 3-1 to 3-67 in Table 3, and the representative compound numbers are 9-1 to 9-67.

[0050] In the above general structural formula I, when O is connected to the 4-position of the benzopyrone ring, and R3=CH3, R5=H, the substituents R1, R2, R6-R9, and W are consistent with Table 3, corresponding to 3-1 to 3-67 in Table 3, and the representative compound numbers are 10-1 to 10-67, respectively.

[0051] In a second aspect, the present invention provides a method for preparing a pyrimidine-containing benzopyrone compound, comprising the following steps: intermediate II and intermediate III react in a solvent under alkaline conditions to obtain a compound of structural formula I, and the reaction formula is as follows:

[0052]

[0053] Preferably, the reaction is carried out under alkaline conditions, and the suitable base is selected from one of potassium hydroxide, sodium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, triethylamine, pyridine, sodium methoxide, sodium ethoxide, sodium hydride, potassium tert-butoxide or sodium tert-butoxide.

[0054] Preferably, the reaction is carried out in a solvent, and a suitable solvent is selected from one of tetrahydrofuran, 1,4-dioxane, acetonitrile, toluene, xylene, benzene, N,N-dimethylformamide, N-methylpyrrolidone, dimethyl sulfoxide, acetone or butanone.

[0055] Preferably, the reaction temperature is between room temperature and the boiling point of the solvent, usually 20°C to 100°C.

[0056] Preferably, the reaction time is 30 min to 20 h, usually 1 to 10 h.

[0057] In a third aspect, the present invention provides a use of the above-mentioned pyrimidine-containing benzopyrone compound in the preparation of a fungicide or an insecticide.

[0058] Preferably, the fungicide or insecticide uses a pyrimidine-containing benzopyrone compound as an active ingredient, the amount of the active ingredient accounts for 0.1% to 99% of the weight of the fungicide or insecticide, and the other components are agricultural, forestry, and hygienic acceptable carriers.

[0059] The compounds of the present invention can be applied in the form of preparations. The compounds shown in the general structural formula I are dissolved or dispersed in a carrier as active ingredients or formulated into preparations so as to be more easily dispersed when used as bactericides or insecticides. For example, these chemical preparations can be made into wettable powders, oil suspensions, water suspensions, aqueous emulsions, aqueous solutions or emulsifiable concentrates. In these preparations, at least one liquid or solid carrier is added, and when necessary, a suitable surfactant can be added.

[0060] Preferably, the fungicide or insecticide is a drug for preventing and controlling pathogens, pests or mites.

[0061] The method of using the fungicide or insecticide of the present invention to control pathogens, pests, and mites is as follows: apply the fungicide or insecticide of the present invention to the pathogens or their growth medium, and the more suitable effective amount usually selected is 10 grams to 1000 grams per hectare, and the preferred effective amount is 20 grams to 500 grams per hectare.

[0062] For certain applications, such as in agriculture, one or more other fungicides, insecticides, miticides, herbicides, plant growth regulators or fertilizers may be added to the fungicide or insecticide of the present invention, thereby producing additional advantages and effects.

[0063] The pyrimidine-containing benzopyrone compounds represented by the general formula I of the present invention can be used in agriculture or other fields to prevent and control diseases including but not limited to the following:

[0064] Oomycete diseases, such as downy mildew (cucumber downy mildew, rape downy mildew, soybean downy mildew), white rust (rape white rust, cabbage white rust), late blight (potato late blight, tomato late blight), etc.; Deuteromycete diseases, such as wilt (tomato wilt, bean wilt, cucumber wilt), root rot (pepper root rot, eggplant root rot, bean root rot, cucumber root rot, bitter melon root rot, cotton black root rot, broad bean root rot), damping-off (cotton seedling damping-off, sesame damping-off, pepper damping-off, cucumber damping-off, cabbage damping-off), anthracnose (cucumber anthracnose, bitter melon anthracnose, zucchini anthracnose, wax gourd Anthracnose, watermelon anthracnose, melon anthracnose, litchi anthracnose), gray mold (cotton boll gray mold, hemp gray mold, tomato gray mold), etc.; basidiomycete diseases, such as rust (wheat stripe rust, wheat stem rust, wheat leaf rust, flower rust, sunflower rust, sugarcane rust, soybean rust), etc.; ascomycete diseases, such as powdery mildew (wheat powdery mildew, rape powdery mildew, sesame powdery mildew), sclerotinia (soybean sclerotinia, peanut sclerotinia, tobacco sclerotinia, pepper sclerotinia, eggplant sclerotinia, bean sclerotinia, pea sclerotinia, cucumber sclerotinia, bitter melon sclerotinia), scab (apple scab, pear scab), etc.

[0065] And for controlling pests including but not limited to the following:

[0066] Coleoptera (Beetles): Acanthoscelides spp. (Weevils), Acanthoscelides obtectus (Common Pea Weevils), Agrilus planipennis (Willow Ash Borer), Agriotes spp. (Wireworms), Anoplophora glabripennis (Asian Longhorn Beetle), Anthonomus spp. (Curculidae), Anthonomus grandis (Cotton Bollworm), Aphidius spp., Apion spp. (Weevils), Apogonia spp. (Grubs), Atacnius sprctulus (Black Velvet Beetle), Atomaria linearis) (pygmy mangold beetle), etc.

[0067] Dermaptcra (earwigs).

[0068] Neuroptera (Dictyoptera) (cockroaches): Blattella germanica (German cockroach), Blatta orientalis (Oriental cockroach), Parcoblatta pennylvanica, etc.

[0069] Diptera (flies): Aedes spp. (mosquitoes), Agromyzafrontella (alfalfa blotch leafminer), Agromyza spp. (leaf miner), Anastrepha spp. (fruit flies), Anastrephasuspensa (Caribbean fruit fly), Anopheless spp. (mosquitoes), Batrocera spp. (fruit flies), etc.

[0070]

[0043] Hemiptera (Stinkbugs): Acrosternum hilare (green stink bug), Blissus leucopterus (chinch bug), Calocoris norvegicus (potato mirid), Cimex hemipterus (tropical bed bug), Cimex lectularius (bed hug), Hesperus, etc.

[0071] Homoptera (aphids, scale flies, whiteflies, leafhoppers): Acrythosiphonpisum (pea aphid), Adelges spp. (adelgids), Aleurodesproletella (cabbage whitefly), Aleurodicus disperses, Aleurothrixusflccosus (woolly whitefly), Aluacaspis spp., etc.

[0072] Lepidoptera (moths and butterflies): Achoeajanata, Adoxophyes spp., Adoxophyes orana, Agrotis spp. (cutworms), Agrotis ipsilon (black cutworm), Alabama argillacea (cotton leafworm), Amorbiacuneana, Amyelosis transitella (navel orangeworm), Anacamptodes defectaria, Anarsia lineatella (peach twig borer), tobacco coindicate, etc.

[0073] The pyrimidine-containing benzopyrone compounds can be advantageously used to protect important crops, livestock and breeding stock in agriculture and horticulture, as well as to protect environments frequented by humans from damage by pathogens, insect pests and mites.

[0074] To achieve the desired effect, the amount of pyrimidine-containing benzopyrone compounds used varies depending on various factors, such as the compound used, the crop to be protected, the type of pest, the degree of infection, climatic conditions, the method of application, and the dosage form used. The amount of pyrimidine-containing benzopyrone compounds used is 10 grams to 1 kilogram of compound per hectare, which can provide sufficient control.

[0075] Compared with the prior art, the present invention has the following beneficial effects:

[0076] The present invention adopts the active substructure splicing principle to rationally combine the substituted pyrimidine group with the benzopyrone skeleton to obtain pyrimidine-containing benzopyrone compounds with good bactericidal and insecticidal activities, which show excellent activity against cucumber downy mildew that often occurs in agricultural production activities, and one of the compounds (9-35) has a higher protective effect than the commercial pesticide flumorph. In addition, it also shows good activity against pests. DETAILED DESCRIPTION

[0077] The following examples are used to illustrate the present invention, but are not intended to limit the scope of the present invention. Unless otherwise specified, the technical means used in the examples are conventional means known to those skilled in the art. The test methods in the following examples are conventional methods unless otherwise specified.

[0078] Part of the intermediate II is commercially available or can be prepared by known methods, for example, by the methods described in JP2000007662A, US4977264A, US6090815A, US20040092402A1, JP09124613A, US5468751A, US4985426A, US4845097A, Journal of the American Chemical Society (1957), 79, 1455, Journal of Chemical Society (1955), p. 3478-3481.

[0079] The compound represented by intermediate III can be prepared by a known method, for details, refer to WO9727173A2.

[0080] The following is the synthesis of intermediate II and intermediate III:

[0081] 1. Synthesis of intermediate 4,5-dichloro-6-methylpyrimidine (one of intermediates II)

[0082] 1) Preparation of 4-hydroxy-5-chloro-6-methylpyrimidine

[0083]

[0084] Under stirring at room temperature, slowly add 8.80g (0.16mol) of sodium methoxide in methanol solution to 11.30g (0.11mol) of formamidine acetate in 50mL of methanol solution, and continue stirring at room temperature for 2h. Then add 11.17g (0.068mol) of the intermediate ethyl 2-chloroacetoacetate to the above solution, and continue stirring at room temperature for 5-7h. After the reaction is completed by TLC monitoring, the solvent is evaporated under reduced pressure, the pH is adjusted to 5-6 with hydrochloric acid, and an orange-yellow solid is obtained by suction filtration. The aqueous phase is extracted with (3×50mL) of ethyl acetate, dried over anhydrous magnesium sulfate, filtered, and desolventized. The residue is dissolved in 50mL of ethyl acetate, left overnight, and filtered to obtain 6.48g of an orange-yellow solid. The yield is 66.00%, and the melting point is 181-184°C.

[0085] 2) Preparation of 4,5-dichloro-6-methylpyrimidine

[0086]

[0087] Dissolve 14.5g (0.1mol) 4-hydroxy-5-chloro-6-methylpyrimidine in 50ml toluene solution, add 50mL phosphorus oxychloride to the reaction bottle under stirring, and heat and reflux for 5-7h. After the reaction is completed, monitor the reaction by TLC, remove toluene and excess phosphorus oxychloride under reduced pressure, pour the reactant into ice water under stirring, extract the aqueous phase with (3×50mL) ethyl acetate, combine the organic phases, dry over anhydrous magnesium sulfate, filter, and desolventize. The residue is separated by column chromatography (eluent is ethyl acetate and petroleum ether, volume ratio is 1:5) to obtain 14.43g of yellow liquid, with a yield of 88.50%.

[0088] 2. Synthesis of intermediate 4-chloroquinazoline (one of intermediates II)

[0089] 1) Preparation of quinazolin-4(3H)-one

[0090]

[0091] 13.7 g (0.1 mol) of anthranilic acid and 20 mL of formamide were placed in a 250 mL three-necked flask, heated to 140°C and reacted for 5-8 hours. After the reaction was completed, the reaction solution was cooled to 100°C, 80 mL of water was added dropwise under stirring, and then cooled to room temperature, filtered, and the filter cake was washed with anhydrous ether to obtain 10.96 g of reddish brown, with a yield of 75.10%.

[0092] 2) Preparation of 4-chloroquinazoline

[0093]

[0094] Take 14.6g (0.1mol) of quinazoline-4(3H)-one in a 250mL single-mouth bottle, add 50mL of thionyl chloride as solvent, and heat to reflux for 4-6h. After the reaction is completed, monitor by TLC, cool the reaction solution, pour it into water, stir for 30min, filter and wash with anhydrous ether to obtain 10.96g of red-brown solid, with a yield of 92.70%.

[0095] 3. Synthesis of intermediate 7-(2-aminoethoxy)-2H-benzopyran-2-one hydrochloride (one of intermediates III)

[0096] 1) Preparation of N-Boc-2-bromoethylamine

[0097]

[0098] 20.5g (0.10mol) of bromoethylamine bromide was placed in 80mL of tetrahydrofuran, and 10.08g (0.12mol) of sodium bicarbonate and 50mL of water were added in sequence. 21.80g (0.1mol) of di-tert-butyl dicarbonate was added dropwise under stirring at room temperature. After the addition was completed, the reaction was continued for 3-9h. After the reaction was completed, the solvent was removed under reduced pressure, and (3×50mL) of ethyl acetate solution was added for extraction, and then the organic phase was washed with 50mL of saturated brine. After the solvent was removed, 21.84g of colorless oily liquid was obtained, with a yield of 97.50%.

[0099] 2) Preparation of 7-(2-aminoethoxy)-2H-benzopyran-2-one hydrochloride

[0100]

[0101] Weigh 7-hydroxycoumarin (16.21g, 0.1mol) in a 500mL single-mouth bottle, add 240mL DMF, potassium carbonate (16.56g, 0.12mol), N-Boc-2-bromoethylamine (22.41g, 0.1mol) and heat to 90℃ for reaction. During the heating reaction, the solid slowly dissolved, the reaction solution turned yellow, and the reaction continued for 4h. The process was monitored by TLC. After the reaction was completed, the mixture was added to water, extracted with ethyl acetate, and the organic phase was washed with water and saturated brine respectively, followed by drying, filtering, and vacuum rotary evaporation. After desolvation, the residue was purified by column chromatography (eluent was ethyl acetate and petroleum ether (boiling range 60-90℃), volume ratio was 1:5) to obtain 25.66g of light yellow solid, with a yield of 84.05%.

[0102] 100 mL of ethyl acetate solution was added to the obtained solid, stirred at room temperature, and 20 mL of concentrated hydrochloric acid was added dropwise. After the solid was dissolved, stirring was continued for 5 h, and the process was monitored by TLC. After the reaction was completed, the solvent was removed under reduced pressure, 50 mL of dichloromethane was added, stirred for 0.5 h, filtered, and the filter cake was washed with dichloromethane to obtain 17.06 g of white solid, with a yield of 84.00%.

[0103] 4. Synthesis of intermediate 4-(2-aminoethoxy)-2H-benzopyran-2-one hydrochloride (one of intermediates III)

[0104]

[0105] Weigh 4-hydroxycoumarin (16.21g, 0.1mol) in a 500mL single-mouth bottle, add 240mL DMF, potassium carbonate (16.56g, 0.12mol), N-Boc-2-bromoethylamine (22.41g, 0.1mol) and heat to 90℃ for reaction. During the heating reaction, the solid slowly dissolved, the reaction solution turned light yellow, and the reaction continued for 4h. The process was monitored by TLC. After the reaction was completed, the mixture was added to water, extracted with ethyl acetate, and the organic phase was washed with water and saturated brine, respectively, followed by drying, filtering, and vacuum rotary evaporation. After desolvation, the residue was purified by column chromatography (eluent was ethyl acetate and petroleum ether (boiling range 60-90℃), volume ratio was 1:5) to obtain 25.03g of light yellow solid, with a yield of 82.00%.

[0106] 100 mL of ethyl acetate solution was added to the obtained solid, stirred at room temperature, and 20 mL of concentrated hydrochloric acid was added dropwise. After the solid was dissolved, stirring was continued for 5 h, and the process was monitored by TLC. After the reaction was completed, the solvent was removed under reduced pressure, 50 mL of dichloromethane was added, stirred for 0.5 h, filtered, and the filter cake was washed with dichloromethane to obtain 17.54 g of a white solid, with a yield of 88.50%.

[0107] Example 1 Synthesis of Compound 3-35

[0108]

[0109] 0.24g (0.001mol) 7-(2-aminoethoxy)-2H-benzopyran-2-one hydrochloride and 0.17g (0.0012mol) potassium carbonate were placed in 20mL DMF, and then 0.16g (0.001mol) 4,5-dichloro-6-methylpyrimidine was added and heated to 90°C for 6h. The process was monitored by TLC. After the reaction was completed, the mixture was added to water, extracted with ethyl acetate, and the organic phase was washed with water and saturated brine, respectively, and then dried, filtered, and evaporated under reduced pressure. The residue after desolventization was purified by column chromatography (eluent was ethyl acetate and petroleum ether (boiling range 60-90°C), volume ratio was 1:6), and 0.28g of light yellow solid was obtained, with a yield of 84.80% and a melting point of 151-152°C.

[0110] The NMR data of compound 3-35 are as follows: 1 H-NMR (600MHz, internal standard TMS, solvent CDCl3) δ (ppm): 8.40 (s, 1H, pyrimidyl-2-H), 7.64 (d, J = 9.5Hz, 1H, coumarin-4-H),7.39(d,J=8.5Hz,1H,coumarin-5-H),6.87(dd,J=8.5,2.4Hz,1H,coumarin -6-H),6.85(d,J=2.4Hz,1H,coumarin-8-H),6.27(d,J=9.5Hz,1H,coumarin-3-H),5.78(s, 1H, NH), 4.22 (t, J = 5.2 Hz, 2H, OCH2), 3.98 (dd, J = 11.0, 5.4 Hz, 2H, CH2NH), 2.47 (s, 3H, CH3).

[0111] Example 2 Synthesis of Compound 3-46

[0112]

[0113] 0.24g (0.001mol) 7-(2-aminoethoxy)-2H-benzopyran-2-one hydrochloride and 0.17g (0.0012mol) potassium carbonate were placed in 20mL DMF, and then 0.16g (0.001mol) 4-chloroquinazoline was added and heated to 90°C for 6h. The process was monitored by TLC. After the reaction was completed, the mixture was added to water, extracted with ethyl acetate, and the organic phase was washed with water and saturated brine, respectively, followed by drying, filtering, and vacuum rotary evaporation. After desolventization, the residue was purified by column chromatography (eluent was ethyl acetate and petroleum ether (boiling range 60-90°C), volume ratio was 1:6), and 0.21g of light yellow solid was obtained, with a yield of 64.30% and a melting point of 148-149°C.

[0114] The NMR data of compound 3-46 are as follows: 1 H-NMR (600MHz, internal standard TMS, solvent CDCl3) δ (ppm): 8.70 (s, 1H, quinazolinyl-2-H), 7.87 (d, J = 8.3Hz, 1H, quinazolinyl-8-H), 7.7 7(dd,J=14.3,7.5Hz,2H,quinazolinyl-5,7-2H),7.63(d,J=9.5Hz,1H,coumarin-4-H),7.50(t,J=7.6Hz,1H,quinazolin yl-6-H),7.38(d,J=8.5Hz,1H,coumarin-5-H),6.88(dd,J=8.5,2.3Hz,1H,coumarin-6-H),6.87(d,J=2.0Hz,1H,coumari n-8-H), 6.26 (d, J = 9.5Hz, 1H, coumarin-3-H), 6.23 (s, 1H, NH), 4.34 (t, J = 5.1Hz, 2H, OCH2), 4.16 (q, J = 5.3Hz, 2H, CH2NH).

[0115] Example 3 Synthesis of Compound 9-35

[0116]

[0117] 0.24g (0.001mol) of 4-(2-aminoethoxy)-2H-benzopyran-2-one hydrochloride and 0.17g (0.0012mol) of potassium carbonate were placed in 20mL of DMF, and then 0.16g (0.001mol) of 4,5-dichloro-6-methylpyrimidine was added, and the mixture was heated to 90°C for 6h. The process was monitored by TLC. After the reaction was completed, the mixture was added to water, extracted with ethyl acetate, and the organic phase was washed with water and saturated brine, respectively, and then dried, filtered, and evaporated under reduced pressure. The residue after desolventization was purified by column chromatography (eluent was ethyl acetate and petroleum ether (boiling range 60-90°C), volume ratio was 1:6), and 0.25g of light yellow solid was obtained, with a yield of 75.40% and a melting point of 160-161°C.

[0118] The NMR data of compound 9-35 are as follows: 1H-NMR (600MHz, internal standard TMS, solvent CDCl3) δ (ppm): 8.43 (s, 1H, pyrimidyl-2-H), 7.80 (d, J = 7.9Hz, 1H,coumarin-5-H),7.57(t,J=7.8Hz,1H,coumarin-7-H),7.33(d,J=8.3Hz,1H,coumari n-8-H),7.29(t,J=7.6Hz,1H,coumarin-6-H),5.75(d,J=5.2Hz,1H,NH),5.74(s,1H,cou marin-3-H), 4.35 (t, J = 5.3 Hz, 2H, OCH2), 4.08 (q, J = 5.5 Hz, 2H, CH2NH), 2.48 (s, 3H, CH3).

[0119] Example 4 Synthesis of Compound 9-46

[0120]

[0121] 0.24g (0.001mol) of 4-(2-aminoethoxy)-2H-benzopyran-2-one hydrochloride and 0.17g (0.0012mol) of potassium carbonate were placed in 20mL of DMF, and then 0.16g (0.001mol) of 4-chloroquinazoline was added, and the mixture was heated to 90°C for reaction for 3-6h. The process was monitored by TLC. After the reaction was completed, the mixture was added to water, extracted with ethyl acetate, and the organic phase was washed with water and saturated brine, respectively, and then dried, filtered, and evaporated under reduced pressure. The residue after desolventization was purified by column chromatography (eluent was ethyl acetate and petroleum ether (boiling range 60-90°C), volume ratio was 1:6), and 0.27g of light yellow solid was obtained, with a yield of 80.50% and a melting point of 252-253°C.

[0122] The NMR data of compound 9-46 are as follows: 1H-NMR (600MHz, internal standard TMS, solvent CDCl3) δ (ppm): 8.72 (s, 1H, quinazolinyl-2-H), 7.88 (d, J=8.3Hz, 1H, quinazoli nyl-8-H),7.81(dd,J=15.1,8.2Hz,2H,coumarin-5-H; quinazolinyl-5-H),7.76(t,J=7.6Hz,1H,quinazo linyl-7-H),7.56-7.45(m,2H,coumarin-7-H; quinazolinyl-6-H),7.25(d,J=7.6Hz,2H,coumarin-6,8-2 H), 6.37 (s, 1H, NH), 5.76 (s, 1H, coumarin-3-H), 4.46 (t, J = 4.9Hz, 2H, OCH2), 4.25 (d, J = 5.2Hz, 2H, CH2NH).

[0123] Other compounds of the present invention can be prepared by referring to the above examples. Physical properties and NMR data of some compounds ( 1 HNMR, 600 MHz, internal standard TMS, ppm) is as follows:

[0124] Compound 3-36: melting point 145-146°C. δ(CDCl3):8.45(s,1H,pyrimidyl-2-H),7.64(d,J=9.4Hz,1H,coumarin-4-H),7.39(d,J=8.5Hz,1H,coumarin-5-H),6.87(dd,J=8.6,2.2Hz,1H,coumarin-6-H),6.85(d,J=2.1Hz,1H,coumarin n-8-H),6.27(d,J=9.5Hz,1H,coumarin-3-H),5.79(s,1H,NH),4.23(t,J=5.2Hz,2H,OCH2),3.9 8(dd,J=10.9,5.4Hz,2H,CH2NH), 2.80(q,J=7.6Hz,2H,CH2CH3), 1.27(t,J=6.0Hz,4H,CH2CH3).

[0125] Compound 3-38: melting point 181-182°C. δ(CDCl3):8.58(s,1H,pyrimidyl-2-H),7.64(d,J=9.5Hz,1H,coumarin-4-H),7.40(d, J=8.5Hz,1H,coumarin-5-H),6.87(dd,J=8.5,2.4Hz,1H,coumarin-6-H),6.85(d,J=2. 3Hz,1H,coumarin-8-H),6.72(t,J=53.7Hz,1H,CHF2),6.28(d,J=9.5Hz,1H,coumarin- 3-H), 6.06 (s, 1H, NH), 4.24 (t, J = 5.2Hz, 2H, OCH2), 4.04 (dd, J = 10.8, 5.4Hz, 2H, CH2NH).

[0126] Compound 3-14: melting point 181-182°C. δ(CDCl3): 8.40 (s, 1H, pyrimidyl-2-H), 7.64 (d, J = 9.5 Hz, 1H, coumarin-4-H), 7.39 (d, J = 8.5 Hz, 1H, coumarin-5-H), 6.84 (dd, J = 8.5, 2.4 Hz, 1H, coumarin-6-H), 6.83 (d, J = 2.2 Hz, 1H, coumarin-8-H), 6.46 (s, 1H, pyrimidyl-5-H), 6.28 (d, J = 9.5 Hz, 1H, coumarin-3-H), 5.41 (s, 1H, NH), 4.21 (t, J = 5.1 Hz, 2H, OCH2), 3.87 (s, 2H, CH2NH).

[0127] Compound 3-22: melting point 208-209° C. δ(CDCl3): 8.32 (s, 1H, pyrimidyl-2-H), 7.64 (d, J=9.5 Hz, 1H, coumarin-4-H), 7.39 (d, J=8.3 Hz, 1H, coumarin-5-H), 6.86 (d, J=2.3 Hz, 1H, coumarin-6-H), 6.85 (s, 1H, coumarin-8-H), 6.27 (d, J=9.5 Hz, 1H, coumarin-3-H), 5.19 (s, 1H, NH), 4.23 (t, J=5.2 Hz, 2H, OCH2), 3.99 (dd, J=10.7, 5.4 Hz, 2H, CH2NH), 2.18 (s, 3H, CH3).

[0128] Compound 3-61: melting point 183-184°C. δ(CDCl3):8.67(t,J=5.1Hz,1H,quinazolinyl-2-H),8.52(s,1H,quinazolinyl-8-H),8.31(d,J=8.9Hz,1H,quinazo linyl-6-H),7.99(d,J=9.5Hz,1H,coumarin-4-H),7.74(d,J=1.8Hz,1H,coumarin-5-H),7.62(d,J=8.6Hz,1H,quina zolinyl-5-H), 7.59 (dd, J=8.8, 1.9Hz, 1H, coumarin-6-H), 7.06 (d, J=1.9Hz, 1H, coumarin-8-H), 6.99 (dd, J=8.6, 2. 2Hz, 1H, coumarin-3-H), 6.29 (d, J = 9.5Hz, 1H, NH), 4.37 (t, J = 5.6Hz, 2H, OCH2), 3.95 (dd, J = 10.9, 5.4Hz, 2H, CH2NH).

[0129] Compound 4-35: melting point 119-120°C. δ(CDCl3): 8.40 (s, 1H, pyrimidyl-2-H), 7.51 (d, J = 8.7 Hz, 1H, coumarin-5-H), 6.89 (d, J = 8.8 Hz, 1H, coumarin-6-H), 6.85 (s, 1H, coumarin-8-H), 6.15 (s, 1H, coumarin-3-H), 5.81 (s, 1H, NH), 4.23 (s, 2H, OCH2), 3.98 (d, J = 5.0 Hz, 2H, CH2NH), 2.47 (s, 3H, pyrimidine-6-CH3), 2.40 (s, 3H, CH3).

[0130] Compound 4-36: white oil. δ(CDCl3):8.45(s,1H,pyrimidyl-2-H),7.51(d,J=8.8Hz,1H,coumarin-5-H),6.89(dd,J=8.8,2.5Hz,1H,coumarin-6-H),6.85(d,J=2.5Hz,1H,coumarin-8-H),6.15(d,J=1.1Hz,1H,coumarin umarin-3-H),5.79(s,1H,NH),4.23(t,J=5.2Hz,2H,OCH2),3.98(dd,J=11.0,5.4Hz,2H,CH2N H), 2.80 (q, J=7.6Hz, 2H, CH2CH3), 2.40 (d, J=1.1Hz, 3H, CH3), 1.26 (t, J=7.6Hz, 3H, CH2CH3).

[0131] Compound 4-38: yellow oil. δ(CDCl3): 8.58 (s, 1H, pyrimidyl-2-H), 7.52 (d, J = 8.8 Hz, 1H, coumarin-5-H), 6.89 (dd, J = 8.8, 2.5 Hz, 1H, coumarin-6-H), 6.85 (d, J = 2.4 Hz, 1H, coumarin-8-H), 6.73 (t, J = 53.7 Hz, 1H, CHF2), 6.16 (s, 1H, coumarin-3-H), 6.07 (s, 1H, NH), 4.24 (t, J = 5.2 Hz, 2H, OCH2), 4.04 (dd, J = 10.8, 5.4 Hz, 2H, CH2NH), 2.41 (d, J = 0.8 Hz, 3H, CH3).

[0132] Compound 4-14: melting point 197-198°C. δ(CDCl3): 8.40 (s, 1H, pyrimidyl-2-H), 7.51 (d, J = 8.7 Hz, 1H, coumarin-5-H), 6.86 (dd, J = 8.7, 2.2 Hz, 1H, coumarin-6-H), 6.83 (d, J = 2.2 Hz, 1H, coumarin-8-H), 6.46 (s, 1H, pyrimidyl-5-H), 6.16 (s, 1H, coumarin-3-H), 5.30 (s, 1H, NH), 4.21 (t, J = 5.0 Hz, 2H, OCH2), 3.86 (s, 2H, CH2NH), 2.40 (s, 3H, CH3).

[0133] Compound 4-22: melting point 222-223°C. δ(CDCl3): 8.31 (s, 1H, pyrimidyl-2-H), 7.50 (d, J = 8.8 Hz, 1H, coumarin-5-H), 6.87 (dd, J = 8.8, 2.3 Hz, 1H, coumarin-6-H), 6.83 (d, J = 2.3 Hz, 1H, coumarin-8-H), 6.14 (s, 1H, coumarin-3-H), 5.28 (s, 1H, NH), 4.23 (t, J = 5.2 Hz, 2H, OCH2), 3.99 (d, J = 5.4 Hz, 2H, CH2NH), 2.40 (s, 4H, CH3), 2.18 (s, 3H, pyrimidine-5-CH3).

[0134] Compound 4-46: melting point 210-211°C. δ (CDCl3): 8.70 (s, 1H, quinazolinyl-2-H), 7.87 (d, J = 8.3Hz, 1H, quinazolinyl-8-H), 7.76 (dd, J = 12. 2,5.6Hz,2H,quinazolinyl-5,7-2H),7.51(d,J=8.6Hz,2H,quinazolinyl-6-H;coumarin-5-H),6.91( dd,J=8.8,2.5Hz,1H,coumarin-6-H),6.88(d,J=2.4Hz,1H,coumarin-8-H),6.15(s,1H,coumarin-3-H ), 6.13 (s, 1H, NH), 4.34 (t, J = 5.1Hz, 2H, OCH2), 4.17 (dd, J = 10.6, 5.3Hz, 2H, CH2NH), 2.40 (s, 3H, CH3).

[0135] Compound 4-61: melting point 164-165°C. δ(CDCl3):8.68(s,1H,quinazolinyl-2-H),7.85(d,J=2.0Hz,1H,quinazolinyl-8-H),7.73(d,J=8.8Hz,1H, quinazolinyl-6-H),7.49(d,J=8.8Hz,1H,coumarin-5-H),7.44(dd,J=8.8,2.0Hz,1H,quinazolinyl-5-H),6 .89(dd,J=8.8,2.5Hz,1H,coumarin-6-H),6.85(d,J=2.4Hz,1H,coumarin-8-H),6.26(s,1H,NH),6.14(s,1H, coumarin-3-H), 4.33 (t, J = 5.1 Hz, 2H, OCH2), 4.15 (dd, J = 10.5, 5.3 Hz, 2H, CH2NH), 2.39 (d, J = 0.8 Hz, 3H, CH3).

[0136] Compound 5-35: melting point 143-144°C. δ(CDCl3):8.40(s,1H,pyrimidyl-2-H),7.49(d,J=8.8Hz,1H,coumarin-5-H),6.86(dd,J=8.8,1.3Hz,1H,coumarin-6-H),6.81(s,1H,coumarin-8-H),5.86(s,1H,NH),4.21(t,J=5.1Hz,2H,OCH2),3.97(q,J=5.3Hz z,2H,CH2NH),2.68-2.57(m,2H,CH2CH2CH2CH3),2.46(s,3H,pyrimidine-6-CH3),2.37(s,3H,coumarin-4 -CH3), 1.58-1.47 (m, 2H, CH2CH2CH3), 1.41 (dd, J=14.8, 7.3Hz, 2H, CH2CH3), 0.94 (t, J=7.2Hz, 3H, CH2CH3).

[0137] Compound 5-36: Melting point 122-123 °C. δ(CDCl3): 8.45 (s, 1H, pyrimidyl-2-H), 7.50 (d, J = 8.9 Hz, 1H, coumarin-5-H), 6.87 (dd, J = 8.8, 2.5 Hz, 1H, coumarin-6-H), 6.82 (d, J = 2.5 Hz, 1H, coumarin-8-H), 5.81 (t, J = 5.1 Hz, 1H, NH), 4.21 (t, J = 5.2 Hz, 2H, OCH2), 3.98 (dd, J = 10.9, 5.4 Hz, 2H, CH2NH), 2.80 (q, J = 7.6 Hz, 2H, pyrimidine-6-CH2CH3), 2.68 - 2.59 (m, 2H, CH2CH2CH2CH3), 2.38 (s, 3H, coumarin-4-CH3), 1.50 (ddd, J = 12.0, 8.8, 6.2 Hz, 2H, CH2CH2CH3), 1.41 (dq, J = 14.5, 7.2 Hz, 2H, CH2CH3), 1.26 (t, J = 7.6 Hz, 3H, pyrimidine-6-CH2CH3), 0.95 (t, J = 7.3 Hz, 3H, CH2CH3).

[0138] Compound 5-38: Melting point 144-145 °C. δ(CDCl3): 8.58 (s, 1H, pyrimidyl-2-H), 7.51 (dd, J = 8.8, 3.1 Hz, 1H, coumarin-5-H), 6.90 - 6.84 (m, 1H, coumarin-6-H), 6.82 (s, 1H, coumarin-8-H), 6.72 (t, J = 53.6 Hz, 1H, CHF2), 6.12 (s, 1H, NH), 4.35 - 4.17 (m, 2H, OCH2), 4.11 - 3.97 (m, 2H, CH2NH), 2.63 (t, J = 7.7 Hz, 2H, CH2CH2CH2CH3), 2.38 (d, J = 3.0 Hz, 3H, coumarin-4-CH3), 1.56 - 1.46 (m, 2H, CH2CH2CH3), 1.41 (dd, J = 14.5, 7.3 Hz, 2H, CH2CH3), 0.99 - 0.91 (m, 3H, CH2CH3).

[0139] Compound 5-22: melting point 151-152°C. δ(CDCl3):8.31(s,1H,pyrimidyl-2-H),7.50(d,J=8.8Hz,1H,coumarin-5-H),6.85(dd,J=8.8,2.5Hz,1H,coumarin-6-H),6.82(d,J=2.5Hz,1H,coumarin-8-H),5.17(s,1H,NH),4.21(t,J=5.1Hz,2H,OCH2),3.98(dd,J=10.6,5.4H z,2H,CH2NH),2.67-2.60(m,2H,CH2CH2CH2CH3),2.38(s,3H,coumarin-4-CH3),2.18(s,3H,pyrimidine-5-CH3),1 .50(ddd,J=11.7,8.9,6.2Hz,2H,CH2CH2CH3), 1.41(dd,J=15.0,7.4Hz,2H,CH2CH3), 0.95(t,J=7.3Hz,3H,CH2CH3).

[0140] Compound 5-16: melting point 222-223°C. δ(CDCl3):7.50(d,J=8.8Hz,1H,coumarin-5-H),6.84(dd,J=8.8,2.5Hz,1H,coumarin-6-H),6.80(d,J=2.4Hz,1H,coumarin-8-H),6.29(s,1H,pyrimidyl-5-H),5.42(s,1H,NH),4.18(t,J=5.1Hz,2H,OCH2),3.82(s, 2H,CH2NH),2.69-2.61(m,2H,CH2CH2CH2CH3),2.51(s,3H,pyrimidyl-2-CH3),2.38(s,3H,coumarin-4-CH3 ), 1.50 (ddd, J=11.9, 8.8, 6.2Hz, 2H, CH2CH2CH3), 1.47-1.38 (m, 2H, CH2CH3), 0.95 (t, J=7.3Hz, 3H, CH2CH3).

[0141] Compound 5-46: Melting point 195-196 °C. δ(CDCl3): 8.70 (s, 1H, quinazolinyl-2-H), 7.87 (d, J = 8.3 Hz, 1H, quinazolinyl-8-H), 7.79 (d, J = 8.3 Hz, 1H, quinazolinyl-5-H), 7.76 (t, J = 7.6 Hz, 1H, quinazolinyl-7-H), 7.49 (t, J = 7.9 Hz, 2H, quinazolinyl-6-H; coumarin-5-H), 6.87 (dd, J = 8.9, 2.1 Hz, 1H, coumarin-6-H), 6.83 (d, J = 2.1 Hz, 1H, coumarin-8-H), 6.28 (s, 1H, NH), 4.32 (t, J = 5.1 Hz, 2H, OCH2), 4.15 (q, J = 5.2 Hz, 2H, CH2NH), 2.72 - 2.58 (m, 2H, CH2CH2CH2CH3), 2.37 (s, 3H, coumarin-4-CH3), 1.55 - 1.46 (m, 2H, CH2CH2CH3), 1.45 - 1.38 (m, 2H, CH2CH3), 0.94 (t, J = 7.3 Hz, 3H, CH2CH3).

[0142] Compound 9-36: Melting point 157-158 °C. δ(CDCl3): 8.47 (s, 1H, pyrimidyl-2-H), 7.80 (dd, J = 7.9, 1.4 Hz, 1H, coumarin-5-H), 7.61 - 7.53 (m, 1H, coumarin-7-H), 7.33 (d, J = 7.8 Hz, 1H, coumarin-8-H), 7.32 - 7.27 (m, 1H, coumarin-6-H), 5.76 (d, J = 5.1 Hz, 1H, NH), 5.74 (s, 1H, coumarin-3-H), 4.35 (t, J = 5.4 Hz, 2H, OCH2), 4.08 (q, J = 5.5 Hz, 2H, CH2NH), 2.81 (q, J = 7.6 Hz, 2H, CH2CH3), 1.27 (t, J = 7.6 Hz, 3H, CH2CH3).

[0143] Compound 9-38: melting point 194-195°C. δ(CDCl3): 8.61 (s, 1H, pyrimidyl-2-H), 7.78 (d, J = 7.9 Hz, 1H, coumarin-5-H), 7.57 (t, J = 7.7 Hz, 1H, coumarin-7-H), 7.33 (d, J = 8.3 Hz, 1H, coumarin-8-H), 7.29 (t, J = 7.5 Hz, 1H, coumarin-6-H), 6.72 (t, J = 53.6 Hz, 1H, CHF2), 6.09 (s, 1H, NH), 5.74 (s, 1H, coumarin-3-H), 4.37 (t, J = 5.3 Hz, 2H, OCH2), 4.14 (q, J = 5.5 Hz, 2H, CH2NH).

[0144] Compound 9-22: melting point 188-189°C. δ(CDCl3): 8.33 (s, 1H, pyrimidyl-2-H), 7.78 (d, J = 7.9 Hz, 1H, coumarin-5-H), 7.55 (t, J = 7.8 Hz, 1H, coumarin-7-H), 7.31 (d, J = 8.4 Hz, 1H, coumarin-8-H), 7.28 (d, J = 7.7 Hz, 1H, coumarin-6-H), 5.74 (s, 1H, coumarin-3-H), 5.26 (s, 1H, NH), 4.36 (t, J = 5.2 Hz, 2H, OCH2), 4.08 (q, J = 5.3 Hz, 2H, CH2NH), 2.19 (s, 3H, CH3).

[0145] Compound 9-16: melting point 207-208°C. δ(CDCl3): 7.96 (s, 1H, pyrimidyl-5-H), 7.81 (d, J = 7.9 Hz, 1H, coumarin-5-H), 7.66 (t, J = 7.8 Hz, 1H, coumarin-7-H), 7.40 (d, J = 8.3 Hz, 1H, coumarin-8-H), 7.35 (t, J = 7.5 Hz, 1H, coumarin-6-H), 6.41 (s, 1H, NH), 6.00 (s, 1H, coumarin-3-H), 4.34 (s, 2H, OCH2), 3.83 (s, 2H, CH2NH), 2.33 (s, 3H, CH3).

[0146] Compound 9-48: melting point 162-163°C. δ(CDCl3):7.84-7.79 (m, 2H, quinazolinyl-8-H; coumarin-5-H), 7.73 (t, J = 7.5 Hz, 1H, quinazolinyl-5-H), 7.68 (d, J = 8.3 Hz, 1H, quinazolinyl-7-H), 7.57 (t, J = 7.7 Hz, 1H, coumarin-7-H), 7.45-7.40 (m, 1H, quina zolinyl-6-H),7.34(d,J=8.3Hz,1H,coumarin-6-H),7.29(d,J=7.4Hz,1H,coumarin-8-H),5.97(s,1H,NH ), 5.85 (s, 1H, coumarin-3-H), 4.46 (t, J = 5.5Hz, 2H, OCH2), 4.24 (q, J = 5.5Hz, 2H, CH2NH), 2.69 (s, 3H, CH3).

[0147] Example 5 Bactericidal activity determination

[0148] The samples of the compounds of the present invention were used to test the in vitro antibacterial activity or in vivo protective effect on various fungal diseases of plants. The in vivo protective activity determination method is as follows: the in vivo potted plant determination method is adopted, that is, the sample of the compound to be tested is dissolved with a small amount of solvent (the type of solvent is such as acetone, methanol, DMF, etc., and is selected according to its solubility for the sample, and the volume ratio of the amount of solvent to the amount of spraying liquid is equal to or less than 0.05), and diluted with water containing 0.1% Tween 80 to prepare the required concentration of the test solution. On the crop sprayer, the test solution is sprayed on the disease host plant (the host plant is a standard potted seedling cultivated in a greenhouse), and the disease is inoculated 24 hours later. According to the characteristics of the disease, the diseased plants that need to be cultivated with temperature control and moisture retention are inoculated and placed in an artificial climate chamber for cultivation. After the disease infection is completed, they are moved to the greenhouse for cultivation. The diseased plants that do not need moisture retention cultivation are directly inoculated and cultivated in the greenhouse. After the control is fully diseased (usually one week), the compound disease prevention effect is evaluated.

[0149] The in vivo protective activity test results of some compounds are as follows:

[0150] In vivo protective activity against cucumber downy mildew:

[0151] At a dosage of 400 ppm: compounds: 3-36, 3-38, 4-46, 5-16, 9-35, 9-38, 9-16 have a control effect of 80% or more on cucumber downy mildew;

[0152] At a dosage of 100 ppm: Compounds: 3-38 and 9-35 have a control effect of 90% or more on cucumber downy mildew;

[0153] At a dosage of 25 ppm: Compound 9-35 had a 75% efficacy against cucumber downy mildew;

[0154] At a dosage of 6.25 ppm: Compound 9-35 had a 20% protection against cucumber downy mildew;

[0155] The control pesticide flumorph had a 70% control effect on cucumber downy mildew at 25 ppm and only 10% control effect at 6.25 ppm, which was slightly lower than compound 9-35.

[0156] Example 6 Insecticidal and Acaricidal Activity Determination

[0157] The compounds of the present invention were used to carry out insecticidal activity tests on several insects. The test method is as follows:

[0158] The test compound was dissolved in a mixed solvent of acetone / methanol (1:1) and then diluted with water containing 0.1% (wt) Tween 80 to the desired concentration.

[0159] The insecticidal activity was determined by airbrush spraying with Plutella xylostella and Armyworm as targets.

[0160] (1) Determination of activity against Plutella xylostella

[0161] Test method: Use a punch to punch cabbage leaves into leaf discs with a diameter of 2 cm and use an airbrush to spray them at a pressure of 10 psi (about 0.7 kg / cm 2 ), spray each leaf disc on both sides, with a spray volume of 0.5 ml. After drying in the shade, 10 2nd-instar test insects were inoculated in each treatment, and each treatment was repeated 3 times. After treatment, they were placed in an observation room at 25°C and a relative humidity of 60-70%. After 72 hours, the number of surviving insects was investigated and the mortality rate was calculated.

[0162] The test results of some compounds on Plutella xylostella are as follows:

[0163] At a dosage of 600 ppm, the mortality rates of compounds: 3-14, 3-22, 3-46, 3-61, 4-14, 4-22, 4-61, 5-35, 5-36, 5-38, 5-22, 5-16, 5-46, 9-35, 9-36, 9-38, 9-22 to diamondback moth were all 100%.

[0164] At a dosage of 100 ppm, the mortality rates of compounds 3-61, 4-14, 5-22, 5-46, 9-22, and 9-38 to diamondback moth were 20% or above.

[0165] At a dosage of 10 ppm, the mortality rates of compounds 3-61, 5-46, and 9-38 to Plutella xylostella were 10% or above.

[0166] (2) Activity determination against armyworms

[0167] Test method: Cut corn leaves into 2 cm long segments and spray with airbrush at a pressure of 10 psi (about 0.7 kg / cm 2 ), spray each leaf segment on both sides, with a spray volume of 0.5 mL. After drying in the shade, 10 2nd-instar test insects were inoculated in each treatment, and each treatment was repeated 3 times. After treatment, they were placed in an observation room at 25°C and a relative humidity of 60-70%. After 72 hours, the number of surviving insects was investigated and the mortality rate was calculated.

[0168] Some of the test results on armyworms are as follows:

[0169] At a dosage of 600 ppm, compounds: 3-14, 3-22, 3-46, 3-61, 4-35, 4-14, 4-22, 4-46, 4-61, 5-35, 5-36, 5-38, 5-22, 5-16, 5-46, 9-35, 9-36, 9-38, 9-22 had a 100% lethality against armyworms.

[0170] At a dosage of 100 ppm, the mortality rates of compounds 3-14, 3-22, 4-14, 4-22, 5-36, and 5-38 to armyworms were 90% or above.

[0171] At a dosage of 10 ppm, the mortality rates of compounds 3-14, 3-22, 4-22, 5-36, and 5-38 to armyworms were 80% and above.

[0172] The embodiments described above are only preferred embodiments of the present invention and are only used to explain the present invention, not to limit the scope of implementation of the present invention. For those skilled in the art, other implementation methods can certainly be easily made by replacement or modification based on the technical contents disclosed in this specification. Therefore, all changes and improvements made on the principles of the present invention should be included in the scope of the patent application of the present invention.

Claims

1. A pyrimidine-containing benzopyrone compound, characterized in that: Its general structural formula is shown in Formula I: Where: Q is R1 is selected from hydrogen, halogen, cyano, nitro, amino, carboxyl, C1-C4 alkyl, halogenated C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 alkoxy or halogenated C1-C4 alkoxy; R2 is selected from hydrogen, halogen, cyano, nitro, amino, carboxyl, formyl, C1-C4 alkyl, halogenated C1-C4 alkyl or C1-C4 alkoxy; W is selected from hydrogen, halogen, C1-C4 alkyl, halogenated C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 alkoxy, C1-C4 alkylthio or C1-C4 alkylsulfonyl; R3 is selected from hydrogen, hydroxy, formyl, C1-C4 alkyl, halogenated C1-C4 alkyl, C1-C4 alkoxy, halogenated C1-C4 alkoxy, C3-C4 cycloalkyl, C1-C4 alkylthio, C2-C4 alkenylthio, C2-C4 alkenyl or C2-C4 alkynyl; R4 and R5 are identically or differently selected from hydrogen, halogen, cyano, nitro, C1-C4 alkyl, halogenated C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 alkoxy or halogenated C1-C4 alkoxy; R6 is selected from hydrogen, halogen, C1-C4 alkyl; R7 is selected from hydrogen, halogen, carboxyl, C1-C4 alkyl, C1-C4 alkoxy; R8 is selected from hydrogen, halogen, nitro, C1-C4 alkyl, C1-C4 alkoxy; R9 is selected from hydrogen, halogen; The connection position of O to the benzopyrone ring is selected from the 4-position or the 7-position.

2. The pyrimidine-containing benzopyrone compound according to claim 1, characterized in that: In the general structural formula I: R1 is selected from methyl, ethyl, chloro or difluoromethyl; R2 is selected from hydrogen, methyl or chlorine; W is selected from hydrogen or methyl; R3 is selected from hydrogen; R4 is selected from hydrogen or methyl; R5 is selected from hydrogen or n-butyl; R6, R8, and R9 are all selected from hydrogen; R7 is selected from hydrogen or chlorine; The connection position of O to the benzopyrone ring is selected from the 4-position or the 7-position.

3. The method for preparing a pyrimidine-containing benzopyrone compound according to any one of claims 1 to 2, characterized in that: The method comprises the following steps: intermediate II and intermediate III react in a solvent under alkaline conditions to obtain a compound of structural formula I, and the reaction formula is as follows:

4. The preparation method according to claim 3, characterized in that: The base is selected from one of potassium hydroxide, sodium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, triethylamine, pyridine, sodium methoxide, sodium ethoxide, sodium hydride, potassium tert-butoxide or sodium tert-butoxide.

5. The preparation method according to claim 3, characterized in that: The solvent is selected from one of tetrahydrofuran, 1,4-dioxane, acetonitrile, toluene, xylene, benzene, N,N-dimethylformamide, N-methylpyrrolidone, dimethyl sulfoxide, acetone or butanone.

6. The preparation method according to claim 3, characterized in that: The reaction temperature is 20°C to 100°C.

7. The preparation method according to claim 3, characterized in that: The reaction time is 30 min to 20 h.

8. Use of the pyrimidine-containing benzopyrone compound according to any one of claims 1 to 2 in the preparation of fungicides or insecticides.

9. The use according to claim 3, characterized in that: The bactericide or insecticide uses pyrimidine-containing benzopyrone compounds as active components, and the weight percentage of the active components in the bactericide or insecticide is 0.1% to 99%.

10. The use according to claim 3, characterized in that: The bactericide or insecticide is a drug for preventing and controlling pathogens, pests or mites.

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