CN111848612A - Compound containing fused heterocyclic structure, preparation method and application thereof, and bactericide - Google Patents

Abstract

The invention relates to the field of pesticides and bactericides and discloses a compound containing a fused heterocyclic structure, a preparation method and application thereof and a bactericide, wherein the compound containing the fused heterocyclic structure has a structure shown in a formula (1). The compound has excellent control effect on plant diseases caused by various oomycete pathogenic bacteria such as phytophthora infestans, phytophthora sojae, phytophthora capsici, phytophthora litchi, peronospora cubensis and the like, is obviously superior to a conventional oomycete disease control medicament dimethomorph, and has good market development prospect.

Description

Compound containing fused heterocyclic structure, preparation method and application thereof, and bactericide

technical field

The invention relates to the field of pesticides and fungicides, in particular to a compound containing a fused heterocyclic structure and a preparation method thereof, an application of the compound containing a fused heterocyclic structure in preventing and treating plant oomycete diseases, and the compound containing a fused heterocyclic structure Application as a pesticide fungicide and a fungicide.

Background technique

Oomycetes are one of the important pathogenic bacteria that cause plant diseases. They have the characteristics of wide parasitic range, strong destructiveness, great damage and rapid development. They can harm most major economic crops such as potatoes, tomatoes, peppers, grapes, tobacco, peppers Wait. At the same time, the diseases caused by it are also difficult to control, thus bringing great losses to agricultural production.

The main plant pathogens of oomycetes are Phytophthora infestans, Phytophthora sojae, Phytophthora capsicum, Pythium ultimum, Phytophthora lychee, and downy mildew of cucumber. Among them, Phytophthora infestans is a typical pathogen, and the outbreak of potato late blight caused the occurrence of the famous Irish famine in history. Other plant pathogens can also cause serious diseases. For example, Phytophthora capsicum can easily cause blight of peppers, tomatoes, eggplants and melons, and downy mildew of melons and fruits caused by cucumber downy mildew.

The prevention and control of oomycete diseases is increasingly difficult. At present, chemical control is still the most simple and effective method in the prevention and control measures. In production, protective fungicides with multiple action sites and systemic fungicides with single action sites are mainly used. However, with the prolonged use of these fungicides and unreasonable long-term use, many pathogens have developed serious drug resistance.

Therefore, the development of new non-cross-resistant oomycete fungicides has become an urgent development direction in this field.

SUMMARY OF THE INVENTION

The purpose of the present invention is to provide a novel compound containing a fused heterocyclic structure to achieve a good effect of preventing and controlling oomycete diseases at low concentrations.

In order to achieve the above object, in the first aspect, the present invention provides a compound of formula (1) containing a fused heterocyclic structure or agrochemically acceptable salts, hydrates and solvates thereof,

In formula (1),

R is selected from hydrogen, methyl, n-propyl, C ₄ -C ₆ alkyl, C ₂ -C ₆ alkenyl, C ₂ -C ₆ alkynyl, C ₁ -C ₆ haloalkyl, C ₂ -C ₆ halo Alkenyl, C ₂ -C ₆ haloalkynyl, C ₁ -C ₄ hydroxyalkyl, C ₂ -C ₄ alkoxyalkyl, C ₂ -C ₆ alkylaminoalkyl, C ₃ -C _{6 Dialkylaminoalkyl} , C3 _{- C8cycloalkylaminoalkyl} , C2 _- C4alkylcarbonyl, aldehyde, aldoxime, nitro, amino, cyano, fluorine, bromine, C2 _- C ₆ aldoxime ether group, C ₂ -C ₆ oxygen-containing cycloalkyl group, C ₃ -C ₆ cycloalkyl group, C ₄ -C ₁₀ cycloalkyl alkyl group, C ₄ -C ₁₀ alkyl cycloalkyl group, C ₅ -C ₁₀ alkylcycloalkylalkyl, C ₃ -C ₆ halocycloalkyl, hydroxyl, C ₁ -C ₄ alkoxy, C ₁ -C ₄ haloalkoxy, C ₁ -C ₄ alkylthio , C ₁ -C ₄ alkylsulfinyl, C ₁ -C ₄ alkylsulfonyl, C ₁ -C ₄ haloalkylthio, C ₁ -C ₄ haloalkylsulfinyl, C ₁ -C ₄ haloalkylsulfonyl Acyl, C ₁ -C ₄ alkylamino, C ₂ -C ₈ dialkylamino, C ₃ -C ₆ cycloalkylamino, C ₂ -C ₄ alkylcarbonylamino, hydroxylamine, C ₁ -C ₄ alkane Oxyamino, C ₂ -C ₄ haloalkylcarbonylamino, C ₂ -C ₄ alkylcarbonyl, C ₂ -C ₆ alkoxycarbonyl, C ₂ -C ₆ alkylcarbonyloxy, C ₂ -C ₆ alkylcarbonyl Sulfanyl, C ₂ -C ₆ alkylaminocarbonyl, C ₃ -C ₈ dialkylaminocarbonyl or C ₃ -C ₆ trialkylsilyl;

R ₁ , R ₂ and R ₃ are each independently selected from H, C ₁ -C ₆ alkyl, C ₂ -C ₆ alkenyl, C ₂ -C ₆ alkynyl, C ₁ -C ₆ haloalkyl, C ₂ - C ₆ haloalkenyl, C ₂ -C ₆ haloalkynyl, C ₁ -C ₄ hydroxyalkyl, C ₂ -C ₄ alkoxyalkyl, C ₂ -C ₆ alkylaminoalkyl, C ₃ -C ₆ dialkylaminoalkyl, C ₃ -C ₈ cycloalkylaminoalkyl, C ₂ -C ₄ alkylcarbonyl, aldehyde, aldoxime, nitro, amino, cyano, halogen, C ₂ - C ₆ aldoxime ether group, C ₂ -C ₆ oxygen-containing cycloalkyl, C ₃ -C ₆ cycloalkyl, C ₄ -C ₁₀ cycloalkyl alkyl, C ₄ -C ₁₀ alkylcycloalkyl, C ₅ -C ₁₀ alkylcycloalkylalkyl, C ₃ -C ₆ halocycloalkyl, hydroxyl, C ₁ -C ₄ alkoxy, C ₁ -C ₄ haloalkoxy, C ₁ -C ₄ alkylthio base, C ₁ -C ₄ alkylsulfinyl, C ₁ -C ₄ alkylsulfonyl, C ₁ -C ₄ haloalkylthio, C ₁ -C ₄ haloalkylsulfinyl, C ₁ -C ₄ haloalkyl Sulfonyl, C ₁ -C ₄ alkylamino, C ₂ -C ₈ dialkylamino, C ₃ -C ₆ cycloalkylamino, C ₂ -C ₄ alkylcarbonylamino, hydroxylamine, C ₁ -C ₄ Alkoxyamino, C ₂ -C ₄ haloalkylcarbonylamino, C ₂ -C ₄ alkylcarbonyl, C ₂ -C ₆ alkoxycarbonyl, C ₂ -C ₆ alkylcarbonyloxy, C ₂ -C ₆ alkyl Carbonylthio, C ₂ -C ₆ alkylaminocarbonyl, C ₃ -C ₈ dialkylaminocarbonyl and C ₃ -C ₆ trialkylsilyl;

R ₄ is 2,6-difluorophenyl or 2-chloro-6-[(methylsulfonyl)oxy]phenyl.

Some exemplary explanations are provided below for some groups of the present invention, and unless otherwise specified, the unlisted parts are explained with reference to the following exemplary explanations.

"C ₄ -C ₆ alkyl" refers to an alkyl group with a total number of carbon atoms of 4-6, including straight-chain alkyl groups, branched-chain alkyl groups, such as straight-chain alkyl groups with a total number of carbon atoms of 4, 5 or 6, The branched chain alkyl group can be, for example, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl and the like. The definition of "C ₁ -C ₆ haloalkyl" is similar to that of "C ₄ -C ₆ alkyl", except that at least one H on "C ₁ -C ₆ haloalkyl" is substituted by a halogen atom, and carbon The total number of atoms varies, for example, 1, 2, 3, 4, 5 or 6 H may be substituted by at least one halogen atom selected from fluorine, chlorine, bromine, iodine, and the carbon atoms of the C ₁ -C ₆ haloalkyl group The total is 1-6. The definition of "C ₁ -C ₄ hydroxyalkyl" is similar to the definition of "C ₄ -C ₆ alkyl", except that at least one H on "C ₁ -C ₄ hydroxyalkyl" is replaced by a hydroxyl group, eg There may be 1, 2 or 3 Hs substituted with hydroxy, and the total number of carbon atoms in the _{C1 -} C4hydroxyalkyl group is 1-4. The definition of "C ₂ -C ₄ alkoxyalkyl" is similar to that of "C ₄ -C ₆ alkyl", except that at least one H on "C ₂ -C ₄ alkoxyalkyl" is replaced by Alkoxy substitution, for example, 1, 2 or 3 H may be substituted by alkoxy, and the total number of carbon atoms of the C ₂ -C ₄ alkoxy alkyl group is 2-4, the C ₂ -C ₄ alkoxy For example, an alkyl group can be represented as R ¹ OR ² -, wherein, R ¹ O is the alkoxy group in the C ₂ -C ₄ alkoxyalkyl group, and R ² is the C ₂ -C ₄ alkoxy group An alkyl group in an alkyl group.

"C ₂ -C ₆ alkenyl" means an alkenyl group having 2 to 6 carbon atoms in total, such as vinyl, propenyl, butenyl and the like. The definition of "C ₂ -C ₆ haloalkenyl" is similar to that of "C ₂ -C ₆ alkenyl", except that at least one H on "C ₂ -C ₆ haloalkenyl" is replaced by a halogen atom Substitution, for example, may have 1, 2, 3, 4, 5 or 6 H replaced by at least one halogen atom selected from fluorine, chlorine, bromine, iodine.

"C ₂ -C ₆ alkynyl" means an alkynyl group having 2-6 carbon atoms in total, such as ethynyl, propynyl, butynyl and the like. The definition of "C ₂ -C ₆ haloalkynyl" is similar to that of "C ₂ -C ₆ alkynyl", except that at least one H on "C ₂ -C ₆ haloalkynyl" is replaced by a halogen atom Substitution, for example, may have 1, 2, 3, 4, 5 or 6 H replaced by at least one halogen atom selected from fluorine, chlorine, bromine, iodine.

"C ₂ -C ₆ alkylaminoalkyl" means a group having 2 to 6 carbon atoms in total, the C ₂ -C ₆ alkylaminoalkyl can be represented, for example, as R ³ -NH-R ⁴ -, and R ^The total number of carbon atoms of ³ and R4 is 2-6. The definition of "C ₃ -C ₆ dialkylaminoalkyl" is similar to that of "C ₂ -C ₆ alkylaminoalkyl", which C ₃ -C ₆ dialkylaminoalkyl can be represented, for example, as R ⁵ -N(R ⁶ )-R ⁷ -, and the total number of carbon atoms of R ⁵ , R ⁶ , and R ⁷ is 3-6.

"C ₃ -C ₈ cycloalkylaminoalkyl" refers to a group having 3-8 carbon atoms in total, and the C ₃ -C ₈ cycloalkylaminoalkyl can be represented, for example, as R ⁸ -R ⁹ -, wherein R ⁸ is a cyclic group containing an N atom, and the N atom in R ⁸ is directly connected to R ⁹ .

"C ₂ -C ₄ alkylcarbonyl" refers to a group with 2-4 carbon atoms in total, the C ₂ -C ₄ alkyl carbonyl can be represented as R ¹⁰ -CO-, for example, R ¹⁰ is C ₂ -C ₄ Alkyl in alkylcarbonyl.

"Aldoximo" is represented as HON=CH-.

"C ₂ -C ₆ aldoxime ether group" refers to a group having 2-6 carbon atoms in total, and the C ₂ -C ₆ aldoxime ether group can be represented, for example, as R ¹¹ -ON=CH-, where R ¹¹ represents an alkane base.

"C ₂ -C ₆ oxygen-containing cycloalkyl" means a group having 2 to 6 carbon atoms in total, and the ring-forming atoms in the group contain at least one oxygen atom. The definition of "C ₃ -C ₆ cycloalkyl" is similar to that of "C ₂ -C ₆ oxygen-containing cycloalkyl", except that the ring atoms of "C ₃ -C ₆ cycloalkyl" are all C atoms, and the total number of carbon atoms in the group is 3-6. The definition of "C ₄ -C ₁₀ cycloalkylalkyl" is similar to that of "C ₂ -C ₆ oxygen-containing cycloalkyl", but the ring atoms of "C ₄ -C ₁₀ cycloalkylalkyl" are all C atom, the total number of carbon atoms of the group is 4-10, the "C ₄ -C ₁₀ cycloalkylalkyl" can be represented as R ¹² -R ¹³ -, wherein R ¹² is cycloalkyl, R ¹³ It is the parent nucleus structure group in the compound connecting the cycloalkyl and the structure represented by formula (1). The definition of "C ₄ -C ₁₀ alkylcycloalkyl" is similar to that of "C ₄ -C ₁₀ cycloalkylalkyl", which C ₄ -C ₁₀ alkylcycloalkyl can be represented, for example, as R ¹⁴ -R ^15- , wherein R ¹⁵ is a cycloalkyl group, and R ¹⁴ is an alkyl group substituted for H in the R ¹⁵ .

"C ₅ -C ₁₀ alkylcycloalkylalkyl" refers to a group with a total number of carbon atoms of 5-10, which can be represented, for example, as R ¹⁶ -R ¹⁷ -R ¹⁸ -, wherein R ¹⁷ is cycloalkane group, the cycloalkyl group is connected to R ¹⁶ and R ¹⁸ as an alkyl group, and R ¹⁸ is directly connected to the core structure in the compound of the structure represented by formula (1).

The definition of "C ₃ -C ₆ halocycloalkyl" is similar to the definition of "C ₃ -C ₆ cycloalkyl", except that the ring-forming carbon in the C ₃ -C ₆ halocycloalkyl At least one H on the atom is substituted with a halogen atom selected from fluorine, chlorine, bromine, iodine.

According to a preferred embodiment, in formula (1),

R is selected from H, methyl, n-propyl, C ₂ -C ₆ alkenyl, C ₂ -C ₆ alkynyl, C ₁ -C ₆ haloalkyl, C ₂ -C ₆ haloalkenyl, C ₂ -C ₆ haloalkynyl, C ₁ -C ₄ hydroxyalkyl, C ₁ -C ₄ acylalkyl, C ₂ -C ₄ alkoxyalkyl, C ₂ -C ₆ alkylaminoalkyl, C ₃ -C ₆ dialkylaminoalkyl, C ₃ -C ₈ cycloalkylamino alkyl, C ₂ -C ₆ alkylamino, C ₃ -C ₆ dialkylamino, hydroxylamine, C ₁ -C ₄ alkoxyamine , C ₁ -C ₄ alkoxy, C ₂ -C ₄ alkylcarbonyl, C ₁ -C ₄ alkylsulfonyl, aldehyde group, C ₁ -C ₄ aldoxime group, hydroxyl, nitro, amino, cyano group , halogen, C ₂ -C ₆ aldoxime ether group, 1,3-dioxocyclopentyl;

R ₁ , R ₂ and R ₃ are each independently selected from H, methyl, ethyl, n-propyl, isopropyl, cyclopropyl, C ₂ -C ₆ alkenyl, C ₂ -C ₆ alkynyl, C ₁ -C ₆ haloalkyl, C ₂ -C ₆ haloalkenyl, C ₂ -C ₆ haloalkynyl, C ₁ -C ₄ hydroxyalkyl, C ₁ -C ₄ acylalkyl, C ₂ -C ₄ Alkoxyalkyl, C ₂ -C ₆ alkylaminoalkyl, C ₃ -C ₆ dialkylaminoalkyl, C ₃ -C ₈ cycloalkylaminoalkyl, C ₂ -C ₆ alkylamino, C ₃ -C ₆ dialkylamino, hydroxylamine, C ₁ -C ₄ alkoxyamine, C ₁ -C ₄ alkoxy, C ₂ -C ₄ alkylcarbonyl, C ₁ -C ₄ alkylsulfonyl, Aldehyde group, aldoxime group, hydroxyl group, nitro group, amino group, cyano group, fluorine, chlorine, bromine, iodine, C ₂ -C ₆ aldoxime ether group and 1,3-dioxocyclopentyl;

R ₄ is 2,6-difluorophenyl or 2-chloro-6-[(methylsulfonyl)oxy]phenyl.

According to another preferred embodiment, in formula (1),

甲氨基、二甲氨基、甲基乙基氨基、羟胺基、甲氧胺基、甲氧基、乙氧基、乙酰基、丙酰基、甲基磺酰基、醛基、-CH＝NOH、-CH＝NOCH₃、羟基、硝基、氨基、氰基、氟、溴或1,3-二氧环戊基；R is selected from H, methyl, n-propyl, n-butyl, tert-butyl, vinyl, propenyl, ethynyl, propynyl, chloromethyl, dichloromethyl, trichloromethyl, bromomethyl , dibromomethyl, tribromomethyl, fluoromethyl, difluoromethyl, trifluoromethyl, 1-chloroethyl, 2-chloroethyl, 1-fluoroethyl, 2-fluoroethyl, 1 ,1-difluoroethyl, 2,2-difluoroethyl, 1,2-difluoroethyl, 2,2,2-trifluoroethyl, 1,1,2,2,2-pentafluoroethyl , acetylmethyl, 1-chloro-vinyl, 2-chloro-vinyl, 2,2-dichlorovinyl, 1,2-dichlorovinyl, 1-fluoro-vinyl, 2-fluoro- Vinyl, 2,2-difluorovinyl, 1,2-difluorovinyl, fluoroethynyl, chloroethynyl, iodoethynyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl group, hydroxy-n-propyl, methoxymethyl, 1-methoxyethyl, 2-methoxyethyl, 3-methoxy-n-propyl, ethoxymethyl, 1-ethoxyethyl base, 2-ethoxyethyl, 3-ethoxyn-propyl, methylaminomethyl, 1-methylaminoethyl, 2-methylaminoethyl, methylamino-n-propyl, dimethylamino aminomethyl, 1-dimethylaminoethyl, 2-dimethylaminoethyl, dimethylamino-n-propyl,

Methylamino, dimethylamino, methylethylamino, hydroxylamine, methoxyamine, methoxy, ethoxy, acetyl, propionyl, methylsulfonyl, aldehyde, -CH=NOH, -CH =NOCH ₃ , hydroxy, nitro, amino, cyano, fluorine, bromine or 1,3-dioxolane;

甲氨基、二甲氨基、甲基乙基氨基、羟胺基、甲氧胺基、甲氧基、乙氧基、乙酰基、丙酰基、甲基磺酰基、醛基、-CH＝NOH、-CH＝NOCH₃、羟基、硝基、氨基、氰基、氟、氯、溴、碘和1,3-二氧环戊基；R ₁ , R ₂ and R ₃ are each independently selected from H, methyl, ethyl, n-propyl, isopropyl, cyclopropyl, n-butyl, tert-butyl, vinyl, propenyl, ethynyl, Propynyl, chloromethyl, dichloromethyl, trichloromethyl, bromomethyl, dibromomethyl, tribromomethyl, fluoromethyl, difluoromethyl, trifluoromethyl, 1-chloroethyl base, 2-chloroethyl, 1-fluoroethyl, 2-fluoroethyl, 1,1-difluoroethyl, 2,2-difluoroethyl, 1,2-difluoroethyl, 2,2 ,2-trifluoroethyl, 1,1,2,2,2-pentafluoroethyl, acetylmethyl, 1-chloro-vinyl, 2-chloro-vinyl, 2,2-dichlorovinyl , 1,2-dichlorovinyl, 1-fluoro-vinyl, 2-fluoro-vinyl, 2,2-difluorovinyl, 1,2-difluorovinyl, fluoroethynyl, chloroacetylene group, iodoethynyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, hydroxy-n-propyl, methoxymethyl, 1-methoxyethyl, 2-methoxyethyl, 3-methoxy-n-propyl, ethoxymethyl, 1-ethoxyethyl, 2-ethoxyethyl, 3-ethoxy-n-propyl, methylaminomethyl, 1-methyl Aminoethyl, 2-methylaminoethyl, methylamino-n-propyl, dimethylaminomethyl, 1-dimethylaminoethyl, 2-dimethylaminoethyl, dimethylamino-n-propyl base,

Methylamino, dimethylamino, methylethylamino, hydroxylamine, methoxyamine, methoxy, ethoxy, acetyl, propionyl, methylsulfonyl, aldehyde, -CH=NOH, -CH = _NOCH3 , hydroxy, nitro, amino, cyano, fluorine, chlorine, bromine, iodine and 1,3-dioxolane;

R ₄ is 2,6-difluorophenyl or 2-chloro-6-[(methylsulfonyl)oxy]phenyl.

Particularly preferably, in formula (1),

-CH₃、-CH₂Cl、-CHClCH₃、-CH₂CH₂Cl、-CH₂F、-CHF₂、-CF₃、-CHFCH₃、-CH₂CH₂F、-CHFCH₂F、-CF₂CH₃、-CH₂CHF₂、-CH₂CF₃、-CF₂CF₃、-CH₂CH₂CH₃、-C(CH₃)₃、-COCH₃、-CH₂COCH₃、-COCH₂CH₃、-CH＝CH₂、-CH＝CF₂、-CH＝CHCH₃、-C≡CH、-C≡C-I、-C≡CCH₃、-OCH₃、-OH、-NO₂、-NH₂、-NHCH₃、-N(CH₃)₂、-N(CH₂CH₃)CH₃、-NHOH、-NHOCH₃、-C≡N、-Br或-H； _R is selected from -CHO, _-CH2OH , -CH(OH) _CH3 , _-CH2CH2OH , _-CH2OCH3 , -CH _{( CH3 ) OCH3} , _-CH2CH2OCH3 , _- CH=NOH, -CH=NOCH ₃ , -CH ₂ NHCH ₃ , -CH ₂ N(CH ₃ ) ₂ ,

_-CH3 , _-CH2Cl , _-CHClCH3 , _-CH2CH2Cl , _-CH2F , _-CHF2 , _-CF3 , _-CHFCH3 , _{-CH2CH2F , -CHFCH2F} , _- CF ₂ CH ₃ , -CH ₂ CHF ₂ , -CH ₂ CF ₃ , -CF ₂ CF ₃ , -CH ₂ CH ₂ CH ₃ , -C(CH ₃ ) ₃ , -COCH ₃ , -CH ₂ COCH ₃ , - COCH ₂ CH ₃ , -CH=CH ₂ , -CH=CF ₂ , -CH=CHCH ₃ , -C≡CH, -C≡CI, -C≡CCH ₃ , -OCH ₃ , -OH, -NO ₂ , _-NH2 , -NHCH3, -N( _CH3 ) ₂ , -N( _{CH2CH3 ) CH3} , -NHOH, _-NHOCH3 , -C≡N, _-Br or -H;

R ₁ , R ₂ and R ₃ are all H;

R ₄ is 2,6-difluorophenyl or 2-chloro-6-[(methylsulfonyl)oxy]phenyl.

Further preferably, in formula (1),

-CH₃、-CH₂Cl、-CHClCH₃、-CH₂CH₂Cl、-CH₂F、-CHF₂、-CF₃、-CHFCH₃、-CH₂CH₂F、-CHFCH₂F、-CF₂CH₃、-CH₂CHF₂、-CH₂CF₃、-CF₂CF₃、-CH₂CH₂CH₃、-C(CH₃)₃、-COCH₃、-CH₂COCH₃、-COCH₂CH₃、-CH＝CH₂、-CH＝CF₂、-CH＝CHCH₃、-C≡CH、-C≡C-I、-C≡CCH₃、-OCH₃、-OH、-NO₂、-NH₂、-NHCH₃、-N(CH₃)₂、-N(CH₂CH₃)CH₃、-NHOH、-NHOCH₃、-C≡N、-Br或-H； _R is selected from -CHO, _-CH2OH , -CH(OH) _CH3 , _-CH2CH2OH , _-CH2OCH3 , -CH _{( CH3 ) OCH3} , _-CH2CH2OCH3 , _- CH=NOH, -CH=NOCH ₃ , -CH ₂ NHCH ₃ , -CH ₂ N(CH ₃ ) ₂ ,

_-CH3 , _-CH2Cl , _-CHClCH3 , _-CH2CH2Cl , _-CH2F , _-CHF2 , _-CF3 , _-CHFCH3 , _{-CH2CH2F , -CHFCH2F} , _- CF ₂ CH ₃ , -CH ₂ CHF ₂ , -CH ₂ CF ₃ , -CF ₂ CF ₃ , -CH ₂ CH ₂ CH ₃ , -C(CH ₃ ) ₃ , -COCH ₃ , -CH ₂ COCH ₃ , - COCH ₂ CH ₃ , -CH=CH ₂ , -CH=CF ₂ , -CH=CHCH ₃ , -C≡CH, -C≡CI, -C≡CCH ₃ , -OCH ₃ , -OH, -NO ₂ , _-NH2 , -NHCH3, -N( _CH3 ) ₂ , -N( _{CH2CH3 ) CH3} , -NHOH, _-NHOCH3 , -C≡N, _-Br or -H;

R ₁ , R ₂ and R ₃ are all H;

R ₄ is 2,6-difluorophenyl.

In another preferred case, in formula (1),

-CH₃、-CH₂Cl、-CHClCH₃、-CH₂CH₂Cl、-CH₂F、-CHF₂、-CF₃、-CHFCH₃、-CH₂CH₂F、-CHFCH₂F、-CF₂CH₃、-CH₂CHF₂、-CH₂CF₃、-CF₂CF₃、-CH₂CH₂CH₃、-C(CH₃)₃、-COCH₃、-CH₂COCH₃、-COCH₂CH₃、-CH＝CH₂、-CH＝CF₂、-CH＝CHCH₃、-C≡CH、-C≡C-I、-C≡CCH₃、-OCH₃、-OH、-NO₂、-NH₂、-NHCH₃、-N(CH₃)₂、-N(CH₂CH₃)CH₃、-NHOH、-NHOCH₃、-C≡N、-Br或-H； _R is selected from -CHO, _-CH2OH , -CH(OH) _CH3 , _-CH2CH2OH , _-CH2OCH3 , -CH _{( CH3 ) OCH3} , _-CH2CH2OCH3 , _- CH=NOH, -CH=NOCH ₃ , -CH ₂ NHCH ₃ , -CH ₂ N(CH ₃ ) ₂ ,

_-CH3 , _-CH2Cl , _-CHClCH3 , _-CH2CH2Cl , _-CH2F , _-CHF2 , _-CF3 , _-CHFCH3 , _{-CH2CH2F , -CHFCH2F} , _- CF ₂ CH ₃ , -CH ₂ CHF ₂ , -CH ₂ CF ₃ , -CF ₂ CF ₃ , -CH ₂ CH ₂ CH ₃ , -C(CH ₃ ) ₃ , -COCH ₃ , -CH ₂ COCH ₃ , - COCH ₂ CH ₃ , -CH=CH ₂ , -CH=CF ₂ , -CH=CHCH ₃ , -C≡CH, -C≡CI, -C≡CCH ₃ , -OCH ₃ , -OH, -NO ₂ , _-NH2 , -NHCH3, -N( _CH3 ) ₂ , -N( _{CH2CH3 ) CH3} , -NHOH, _-NHOCH3 , -C≡N, _-Br or -H;

R ₁ , R ₂ and R ₃ are all H;

R4 is ₂ -chloro-6-[(methylsulfonyl)oxy]phenyl.

The present invention has no particular limitation on the methods for preparing the aforementioned compounds, and those skilled in the art can obtain suitable methods for preparing the compounds of the present invention in combination with conventional means in the field of organic synthesis after understanding the technical solutions of the present invention.

The present invention exemplarily provides a method for preparing the aforementioned compounds of the present invention as follows, which should not be construed as a limitation of the present invention by those skilled in the art.

A method for preparing a compound represented by formula (1) containing a fused heterocyclic structure, the method comprising: under nucleophilic substitution reaction conditions, mixing the compound represented by formula (2-1) with the compound represented by formula (2-2) The compounds shown in the contact reaction,

The definitions of R ₄ in the compound represented by the formula (2-1) and R, R ₁ , R ₂ , and R ₃ in the compound represented by the formula (2-2) are the same as those of the structure represented by the formula (1). The definitions of R, R ₁ , R ₂ , R ₃ and R ₄ in the compound containing a fused heterocyclic structure are the same.

When the nucleophilic substitution reaction of the present invention is carried out under basic conditions, the basic conditions can also be provided by a solvent such as tetrahydrofuran. Preferably, the nucleophilic substitution reaction is carried out in the presence of a basic reagent and in an anhydrous environment. Preferably, the alkaline reagent is at least one of sodium hydride, potassium carbonate and cesium carbonate.

Preferably, the contact reaction is carried out in the presence of a solvent, and the solvent is preferably at least one selected from the group consisting of dichloromethane, tetrahydrofuran, N,N-dimethylformamide, acetonitrile and acetone.

Preferably, the conditions of the contact reaction include: the reaction temperature is 0-60° C., and the reaction time is 2-48 h.

In the present invention, the compounds represented by the formula (2-1) and the formula (2-2) can be obtained from commercial sources, or can be synthesized according to the structural formula using the methods of the prior art. The present invention exemplarily provides a method for preparing the compound represented by formula (2-1) in the examples, which should not be construed as a limitation of the present invention by those skilled in the art.

Preferably, the molar ratio of the compound represented by formula (2-1) to the compound represented by formula (2-2) is 1:(1-3); more preferably, it is 1:(1.2-2.4).

In the second aspect of the present invention, the product obtained after the contact reaction can also be subjected to a post-treatment method commonly used in the art to obtain a product with higher purity. For example, the post-treatment operation method includes: extraction , washing, rotary evaporation, column chromatography, recrystallization, etc., which are not particularly limited in the present invention, as long as the aforementioned fused heterocyclic structure-containing compound of the present invention can be obtained.

The second aspect of the present invention provides the use of the aforementioned fused heterocyclic structure-containing compound or agrochemically acceptable salts, hydrates and solvates thereof in controlling plant oomycete diseases.

Preferably, the plant oomycete disease is caused by at least one pathogen selected from the group consisting of Phytophthora infestans, Phytophthora sojae, Phytophthora capsicum, Pythium ultimum, Phytophthora nicotianae, Phytophthora lychee and Cucumber downy mildew. disease.

The third aspect of the present invention provides the use of the aforementioned fused heterocyclic structure-containing compound or agrochemically acceptable salts, hydrates and solvates thereof as pesticides and fungicides.

The fourth aspect of the present invention provides a bactericide, which is composed of an active ingredient and an auxiliary material, and the active ingredient includes the compound containing a fused heterocyclic structure represented by the aforementioned formula (1) of the present invention or its agricultural At least one of chemically acceptable salts, hydrates and solvates.

Preferably, the content of the active ingredient is 1-99.9% by weight, more preferably the content of the active ingredient is 5-95% by weight.

Preferably, the dosage form of the bactericide is selected from at least one of emulsifiable concentrate, suspending agent, wettable powder, powder, granule, water, poison bait, mother liquor and mother powder.

In the present invention, the auxiliary materials can be various auxiliary materials commonly used in the field, such as surfactants, solvents and the like.

Experiments of the present invention show that the compounds of the present invention have excellent control effects on plant diseases caused by various oomycete pathogens such as Phytophthora infestans, Phytophthora capsicum, Phytophthora litchi, and downy mildew of cucumber, which are obviously better than those of conventional eggs. The fungal disease control agent dimethomorph has a good market development prospect.

The compounds provided by the present invention can also effectively control mutant strains resistant to existing fungicides. Therefore, the compounds of the present invention are of great significance for the development of novel oomycete fungicides without cross-resistance.

Detailed ways

The endpoints of ranges and any values disclosed herein are not limited to the precise ranges or values, which are to be understood to encompass values proximate to those ranges or values. For ranges of values, the endpoints of each range, the endpoints of each range and the individual point values, and the individual point values can be combined with each other to yield one or more new ranges of values that Ranges should be considered as specifically disclosed herein.

The present invention will be described in detail below by way of examples.

In the following examples, unless otherwise specified, various raw materials used are from commercial sources, and the purity is chemically pure.

Example 1

This example is used to illustrate the preparation method of the compound represented by formula (2-1). Wherein, R ₄ in the compound represented by formula (2-1) is 2,6-difluorophenyl.

(1) At 25°C, add 1,3-dichloroacetone (1mol) to 1L of 2M hydrochloric acid ether solution, then add tert-butyl nitrite (1mol), continue the reaction at 25°C for 10h, remove after the reaction is complete ether, the crude product of the compound represented by the formula (2-4) was obtained after cooling, and washed with 1-chlorobutane, filtered, and the filter cake was collected; and the filtrate was recrystallized, filtered, and the filter cake was dried to obtain the formula (2). The compound represented by -4), the pure product of the compound represented by the formula (2-4) was obtained after combining two batches.

(2) At 25°C, sodium bicarbonate (5 mol) was added to 1 L of the acetonitrile solution of the compound represented by the formula (2-4) (1 mol), and then 2,6-difluorostyrene (1 mol) was slowly added , continue to stir the reaction for 4h, the reaction is completed, filter, remove the solvent in the filtrate to obtain the compound represented by formula (2-5), which is directly used in the next step.

(3) Compound (1 mol) represented by formula (2-5), 4-aminothiocarbonyltetrahydropyridine-1(2H)-carboxylic acid tert-butyl ester (1.1 mol) and sodium bromide (0.1 mol) were sequentially added It was added to 2.5L acetone, the reaction system was heated under reflux for 12h, the reaction was completed, acetone was removed, 2L water was added, extracted with 500mL*3 ethyl acetate, the organic phases were combined, dried and concentrated to obtain the formula (2-6). The crude product of the compound is further purified by column chromatography with the elution system formed by silica gel, petroleum ether and ethyl acetate, and finally the pure compound shown in formula (2-6) is obtained;

(4) Dissolve the compound (0.5 mol) represented by formula (2-6) in 500 mL of methanol, add 100 mL of hydrogen chloride/methanol solution (4M), and stir at 25°C for 6 h. After the reaction is completed, slowly add 2M hydrogen peroxide dropwise. The aqueous sodium solution was adjusted to pH=7, extracted with 500 mL*5 of ethyl acetate, the organic phases were combined, dried and concentrated to obtain the compound represented by formula (2-7).

(5) Add chloroacetyl chloride (0.15 mol) dropwise to 500 mL of anhydrous dichloromethane solution of the compound represented by formula (2-7) (0.1 mol), keep the temperature at -5～0°C, and continue to slowly add carbonic acid Potassium aqueous solution (0.12mol, w/v 20%), and continue to maintain the temperature at -5 ~ 0 ° C, the dropwise addition was completed, the temperature was raised to room temperature, the reaction was completed, the aqueous phase was removed by liquid separation, and the organic phase was washed with saturated brine. After drying with sodium sulfate and concentration under reduced pressure, the crude compound of formula (2-1) is obtained, then ethyl acetate is added, stirred into a uniform slurry, filtered, and the filter cake is dried to obtain formula (2-1) The compound shown is pure.

Example 2

This example is used to illustrate the preparation method of the compound represented by formula (2-1). Wherein, R ₄ in the compound represented by formula (2-1) is 2-chloro-6-[(methylsulfonyl)oxy]phenyl.

(1) At 0°C, under nitrogen protection, methylmagnesium bromide (1.1 mol) was slowly added dropwise to the anhydrous tetrahydrofuran solution of 3-chloro-2-vinylphenol (1 mol). After reaching room temperature, the reaction was continued for 10 h. After the reaction was completed, saturated ammonium chloride was added to quench, and extracted with ethyl acetate. The organic phase was dried and concentrated to obtain crude 3-chloro-2-(1-hydroxyethyl)-phenol, directly used in the next reaction;

The above compound 3-chloro-2-(1-hydroxyethyl)-phenol (1mol) was dissolved in N,N-dimethylacetamide, the temperature was raised to 160°C, methanesulfonic acid (1mol) was slowly added, and stirring was continued. After the reaction was completed for 2 h, 1 L of water was added, extracted with ethyl acetate, the organic phase was washed with saturated sodium bicarbonate, dried and concentrated to obtain the compound 3-chloro-2-vinyl-phenol;

The above compound 3-chloro-2-vinyl-phenol (1 mol) was dissolved in tetrahydrofuran, and triethylamine (1.2 mol) was added, the temperature was lowered to 0-5 °C, and methanesulfonyl chloride (1.2 mol) was added slowly. And keep the temperature at 0-5 ° C, after the completion of the dropwise addition, continue to stir the reaction 30min, the reaction is completed, add 250mL 1N dilute hydrochloric acid, and extract with ethyl acetate, the organic phase is dried, filtered and purified by column chromatography to obtain formula ( 2-8). The compound shown in 2-8).

(2) At 25°C, sodium bicarbonate (5 mol) was added to 1 L of the acetonitrile solution of the compound (1 mol) represented by the formula (2-4), and then the compound (1 mol) represented by the formula (2-8) was added Add slowly, continue to stir the reaction for 4h, after the reaction is completed, filter and remove the solvent in the filtrate to obtain the compound represented by formula (2-9), which is directly used in the next reaction.

(3) Compound (1 mol) represented by formula (2-9), 4-aminothiocarbonyltetrahydropyridine-1(2H)-carboxylic acid tert-butyl ester (1.1 mol) and sodium bromide (0.1 mol) were sequentially It was added to 2.5L acetone, the reaction system was heated under reflux for 12h, the reaction was completed, acetone was removed, 2L water was added, extracted with 500mL*3 ethyl acetate, the organic phases were combined, dried and concentrated to obtain the formula (2-10) The crude product of the compound is further purified by column chromatography with the elution system formed by silica gel, petroleum ether and ethyl acetate to finally obtain the pure compound shown in formula (2-10);

(4) The compound (0.5 mol) represented by formula (2-10) was dissolved in 500 mL of methanol, 100 mL of hydrogen chloride/methanol solution (4M) was added, and the reaction was stirred at 25° C. for 6 h. After the reaction was completed, 2M hydroxide was slowly added dropwise. The aqueous sodium solution was adjusted to pH=7, extracted with 500 mL*5 of ethyl acetate, the organic phases were combined, dried and concentrated to obtain the compound represented by formula (2-11).

(5) Add chloroacetyl chloride (0.15 mol) dropwise to a solution of the compound (0.1 mol) represented by the formula (2-11) in 500 mL of anhydrous dichloromethane, keep the temperature at -5 to 0 °C, and continue to slowly add carbonic acid Potassium aqueous solution (0.12mol, w/v 20%), and continue to maintain the temperature at -5 ~ 0 ° C, the dropwise addition was completed, the temperature was raised to room temperature, the reaction was completed, the aqueous phase was removed by liquid separation, and the organic phase was washed with saturated brine. After drying with sodium sulfate and concentration under reduced pressure, the crude compound of formula (2-1) is obtained, then ethyl acetate is added, stirred into a uniform slurry, filtered, and the filter cake is dried to obtain formula (2-1) The compound shown is pure.

Example 3

This embodiment is used to illustrate formula (3-1), formula (3-12), formula (3-15), formula (3-17), formula (3-18), formula (3-19), formula ( 3-20), formula (3-23), formula (3-25), formula (3-27), formula (3-28), formula (3-29), formula (3-30), (3- 31), formula (3-32), formula (3-33), formula (3-34), formula (3-35), formula (3-36), formula (3-37), formula (3-38) ), formula (3-39), formula (3-40), formula (3-41), formula (3-42), formula (3-43), formula (3-44), formula (3-45) , formula (3-46), formula (3-47), formula (3-48), formula (3-49), formula (3-50), formula (3-51), formula (3-52), The preparation method of the compound represented by formula (3-53).

Specifically, taking the preparation of the compound represented by formula (3-1) as an example

At 0 °C, sodium hydride (1.5 mmol) was added to a solution of 1H-pyrazolo[3,4-b]pyridine-3-carboxaldehyde (1.2 mmol) in 10 mL of anhydrous tetrahydrofuran, and the reaction was carried out at 0 °C for 0.5 h , and then the compound (1 mmol) represented by formula (2-1) was added, and the reaction was continued at 0 °C for 6 h. After the reaction is completed, the compound represented by formula (3-1) is obtained through extraction, washing, concentration, and purification by column chromatography.

In addition, taking the preparation of the compound represented by the formula (3-36) as an example

At 0 °C, sodium hydride (1.5 mmol) was added to a solution of 1H-pyrazolo[3,4-b]pyridine-3-carboxaldehyde (1.2 mmol) in 10 mL of anhydrous tetrahydrofuran, and the reaction was carried out at 0 °C for 0.5 h , and then the compound (1 mmol) represented by formula (2-1) was added, and the reaction was continued at 0 °C for 6 h. After the reaction is completed, the compound represented by the formula (3-36) is obtained through extraction, washing, concentration, and purification by column chromatography.

Formula (3-1): white solid, yield 70%, mp173-174°C, ¹ H NMR (400MHz, CDCl ₃ )δ 10.20(s, 1H), 8.67-8.54(m, 2H), 7.68(s ,1H),7.39–7.28(m,2H),6.92(t,J=8.4Hz,2H),6.15–6.02(m,1H),5.56(s,2H),4.60(d,J=13.2Hz, 1H), 4.08 (d, J＝13.6Hz, 1H), 3.82 (dd, J＝17.2, 12.0Hz, 1H), 3.64 (dd, J＝17.2, 9.2Hz, 1H), 3.46–3.32 (m, 2H) ), 2.99–2.87 (m, 1H), 2.32 (d, J=12.8Hz, 1H), 2.20 (d, J=12.8Hz, 1H), 2.02–1.78 (m, 2H). ¹³ C NMR (100MHz, CDCl ₃ )δ186.79,174.22,174.15,164.05,162.58(d,J=8.1Hz,1H),160.08(d,J=8.1Hz,1H),152.22,150.01,145.18,142.59,131.62,130.62(t,J =10.1Hz,1H),120.07,117.97,115.70(t,J=16.2Hz,1H),113.77,111.97(d,J=6.1Hz,1H),,111.78(d,J=6.1Hz,1H), 72.87, 49.14, 44.73, 42.09, 41.53, 40.18, 32.46, 31.74. HRMS calculated for C ₂₇ H ₂₂ F ₂ N ₆ O ₂ S[M+Na] ⁺ 559.13344. Found 559.13344.

Formula (3-12): white solid, yield 87%, mp 143-145°C, ¹ H NMR (600 MHz, CDCl ₃ ) δ 8.50 (d, J=4.8 Hz, 1H), 8.01 (d, J=7.8 Hz,1H),7.67(s,1H),7.28-7.32(m,1H),7.10(dd,J=7.8,4.8Hz,1H),6.92(t,J=8.1Hz,2H),6.08(dd , J＝12.0, 9.0Hz, 1H), 5.37(s, 2H), 4.61(d, J＝13.8Hz, 1H), 4.06(d, J＝13.8Hz, 1H), 3.81(dd, J＝17.4, 12.0Hz, 1H), 3.64(dd, J=17.4, 9.0Hz, 1H), 3.29-3.34(m, 2H), 2.85(t, J=12.6Hz, 1H), 2.59(s, 3H), 2.24( d, J=13.8Hz, 1H), 2.15 (d, J=13.8Hz, 1H), 1.80-1.75 (m, 2H); ¹³ C NMR (150MHz, CDCl ₃ ) δ 174.15, 164.86, 161.65 (d, J= 4.5Hz), 160.00(d, J＝4.5Hz), 151.86, 151.15, 148.24, 144.58, 141.25, 130.25(t, J＝9.1Hz), 129.32, 117.76, 115.77, 115.25(t, J＝16.2Hz), 114.96, 111.50 (d, J=3.0Hz), 111.36 (d, J=3.0Hz), 72.37, 47.64, 44.12, 41.45, 41.03, 39.80, 32.00, 31.38, 12.11. HRMS calculated value C ₂₆ H ₂₄ F ₂ N ₆ O ₂ S[M+H] ⁺ 523.17223. Found 523.17055.

Formula (3-15): white solid, yield 78%, mp 146-147°C, ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.72 (dd, J=4.4, 1.6 Hz, 1H), 8.36 (d ,J=8.0Hz,1H),8.04(s,1H),7.43-7.54(s,2H),7.15(t,J=8.4Hz,2H),6.02(dd,J=12.0,8.4Hz,1H) ,5.70(q,J＝16.8Hz,2H),4.34(d,J＝13.2Hz,1H),4.13(d,J＝13.6Hz,1H),3.91(dd,J＝17.2,12.0Hz,1H) ,3.55(dd,J＝17.2,8.8Hz,1H),3.45-3.35(m,2H),2.85(t,J＝11.6Hz,1H),2.17(d,J＝12.0Hz,1H),2.09( d, J=12.0Hz, 1H), 1.95-1.83 (m, 1H), 1.66-1.53 (m, 1H). ¹³ C NMR (100MHz, CDCl ₃ ) δ 174.22, 163.96, 162.55 (d, J=8.1Hz) ,160.05(d,J＝8.1Hz),152.25,151.06,150.17,145.11,133.72(q,J＝39.4Hz),130.58(t,J＝10.1Hz),129.54,122.58,119.90,118.90,117.92,115.68 (t,J＝16.2Hz),112.32,111.93(t,J＝6.1Hz),111.74(t,J＝6.1Hz),72.84,48.99,44.62,41.98,41.51,40.16,32.41,31.74.HRMS calculated value C ₂₆ H ₂₁ F ₅ N ₆ O ₂ S[M+Na] ⁺ 599.12591. Found 599.12602.

Formula (3-17): white solid, yield 71%, mp 141-143°C, ¹ H NMR (400 MHz, CDCl ₃ ) 8.51 (dd, J=4.8, 1.6 Hz, 1H), 8.05 (dd, J=8.0 ,1.6Hz,1H),7.68(s,1H),7.35–7.27(m,1H),7.10(dd,J=8.0,4.8Hz,1H),6.92(t,J=8.4Hz,2H),6.08 (dd,J＝12.0,9.2Hz,1H),5.40(s,2H),4.61(d,J＝13.6Hz,1H),4.06(d,J＝13.6Hz,1H),3.81(dd,J＝ 17.2, 12.0Hz, 1H), 3.64 (dd, J=17.2, 9.2Hz, 1H), 3.38–3.25 (m, 2H), 2.96 (t, J=7.6Hz, 2H), 2.85 (t, J=12.0 Hz, 1H), 2.19 (dd, J=28.0, 13.2 Hz, 2H), 1.88–1.74 (m, 4H), 1.00 (t, J=7.6 Hz, 3H). ¹³ C NMR (100 MHz, CDCl ₃ )δ174 .46,173.92,165.21,162.61(d,J＝7.1Hz),160.11(d,J＝7.1Hz),152.29,151.44,148.44,146.04,145.13,130.59(d,J＝10.1Hz),130.17,117.82,116.16 ,115.77(d,J＝16.2Hz),115.20,111.97(d,J＝5.1Hz),111.78(d,J＝6.1Hz),72.87(t,J＝3.0Hz),48.34,44.65,41.97,41.59 , 41.57, 40.35, 32.49, 31.86, 29.63, 22.46, 20.92, 14.08. HRMS calculated for C ₂₈ H ₂₈ F ₂ N ₆ O ₂ S[M+H] ⁺ 551.20353. Found 551.20533.

Formula (3-18): white solid, yield 88%, mp138-139°C, ¹ H NMR (600MHz, CDCl ₃ )δ8.45(s, 1H), 8.16(d, J=8.4Hz, 1H), 7.64(s, 1H), 7.09–6.98(m, 2H), 6.88(t, J=8.4Hz, 2H), 6.04(t, J=10.8Hz, 1H), 5.36(d, J=15.6Hz, 1H) ),5.32(d,J＝16.8Hz,1H),4.58(d,J＝13.8Hz,1H),4.05(d,J＝13.8Hz,1H),3.77(t,J＝14.8Hz,1H), 3.61(dd,J=17.4,9.0Hz,1H),3.32-3.22(m,2H),2.81(t,J=13.2Hz,1H),2.14(dd,J=26.8,13.2Hz,2H),1.75 (t, J=12.6Hz, 2H), 1.48 (s, 9H). ¹³ C NMR (150 MHz, CDCl ₃ ) δ 174.47, 165.37, 162.27, 160.61, 152.98, 152.36, 151.98, 148.22, 145.21, 131.37, 130.61, 117.7 ,115.82,113.42,111.99,111.84,72.91,48.43,44.79,41.99,41.64,40.40,34.23,32.52,31.94,30.11.HRMS calculated C ₂₉ H ₃₀ F ₂ N ₆ O ₂ S[M+H] ⁺ 565.219 .Measured value 565.21901.

Formula (3-19): white solid, yield 90%, mp 155-156°C, ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.67 (d, J=7.6 Hz, 1H), 8.57 (d, J=4.4 Hz, 1H), 7.66(s, 1H), 7.36–7.27(m, 2H), 6.91(t, J=8.4Hz, 2H), 6.08(dd, J=12.0, 9.6Hz, 1H), 5.52(s) ,2H),4.60(d,J＝13.6Hz,1H),4.07(d,J＝13.6Hz,1H),3.80(dd,J＝17.2,12.0Hz,1H),3.63(dd,J＝17.2, 9.2Hz, 1H), 3.50–3.28 (m, 2H), 2.98–2.80 (m, 1H), 2.71 (s, 3H), 2.31 (d, J=12.4Hz, 1H), 2.19 (d, J=12.4 Hz, 1H), 2.02–1.76(m, 2H). ¹³ C NMR(150MHz, CDCl ₃ )δ194.39,174.10,164.09,161.95,160.28,152.05,151.48,149.26,144.94,141.89,132.16,130.50(t,J = 7.1Hz), 119.48, 117.93, 115.49 (t, J = 10.1Hz), 114.29, 111.78, 111.63, 72.67, 48.92, 44.52, 41.84, 41.32, 40.01, 32.27, 31.59, 26.27. HRMS calculated value C ₂₇ H ₂₄ F ₂ N ₆ O ₃ S[M+Na] ⁺ 573.14909. Found 573.14878.

Formula (3-20): white solid, yield 87%, mp 149-150°C, ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.53 (d, J=4.5 Hz, 1H), 8.26 (d, J=8.0 Hz,1H),7.67(s,1H),7.35–7.28(m,1H),7.17(dd,J=8.0,4.8Hz,1H),7.00(dd,J=18.0,11.6Hz,1H),6.92 (t, J=8.4Hz, 2H), 6.13–6.01 (m, 2H), 5.56 (d, J=11.6Hz, 1H), 5.40 (s, 2H), 4.60 (d, J=13.2Hz, 1H) ,4.06(d,J＝13.2Hz,1H),3.81(dd,J＝17.2,12.0Hz,1H),3.63(dd,J＝17.2,9.2Hz,1H),3.32(t,J＝11.6Hz, 2H), 2.86(t, J=12.0Hz, 1H), 2.23(d, J=13.2, 1H), 2.16(d, J=13.2, 1H), 1.92–1.74(m, 2H). ¹³ C NMR( 100MHz, CDCl ₃ )δ174.38,164.91,162.61(d,J=8.1Hz),160.12(d,J=8.1Hz),152.29,151.77,148.86,145.15,142.67,130.60(t,J=10.1Hz),130.56 ,129.08,117.85,117.61,117.30,115.76(t,J＝16.2Hz),113.80,111.98(d,J＝6.1Hz),111.79(t,J＝6.1Hz),72.87(t,J＝3.0Hz) , 48.42, 44.67, 41.99, 41.56, 40.31, 32.50, 31.82. HRMS calculated for C ₂₇ H ₂₄ F ₂ N ₆ O ₂ S[M+H] ⁺ 535.17223. Found 535.17301.

Formula (3-23): white solid, yield 89%, mp215-217°C, ¹ H NMR (400MHz, CDCl ₃ )δ8.55(d, J=3.6Hz, 1H), 8.13(d, J=8.0 Hz, 1H), 7.67 (s, 1H), 7.35–7.25 (m, 1H), 7.23–7.13 (m, 1H), 6.91 (t, J=8.0Hz, 2H), 6.12–5.92 (m, 1H) ,5.44(s,2H),4.57(d,J＝12.8Hz,1H),4.05(d,J＝13.2Hz,1H),3.87–3.71(dd,J＝17.2,8.4Hz,1H),3.63( dd, J=17.2, 9.2Hz, 1H), 3.40 (s, 1H), 3.37–3.20 (m, 2H), 2.87 (t, J=11.6Hz, 1H), 2.26–2.11 (m, 2H), 1.95 -1.72 (m, 2H). ¹³ CNMR (100MHz, CDCl ₃ ) δ 174.28, 164.44, 162.64 (d, J=7.1 Hz), 160.14 (d, J=7.1 Hz), 152.32, 150.76, 149.65, 145.20, 130.58 ( t,J＝11.1Hz),129.83,127.41,117.98,117.81,117.44,115.79(t,J＝16.2Hz),111.98(d,J＝5.1Hz),111.78(d,J＝5.1Hz),81.80, 74.79, 72.89, 48.81, 44.69, 42.01, 41.59, 40.25, 32.48, 31.80. HRMS calculated for C ₂₇ H ₂₂ F ₂ N ₆ O ₂ S[M+H] ⁺ 533.15658. Found 533.15512.

Formula (3-25): pale yellow solid, yield 78%, mp 131-132°C, ¹ H NMR (600MHz, DMSO-d ₆ )δ8.79(d, J=4.2Hz, 1H), 8.63(d, J=8.4Hz, 1H), 8.05(s, 1H), 7.68-7.61(m, 1H), 7.55-7.43(m, 1H), 7.17(t, J=9.0Hz, 2H), 6.01(t, J =10.8Hz,1H),5.84(d,J=16.8Hz,1H),5.77(d,J=16.8Hz,1H),4.33(d,J=13.8Hz,1H),4.12(d,J=13.8 Hz, 1H), 3.91 (dd, J=17.4, 13.2Hz, 1H), 3.55 (dd, J=17.4, 8.4Hz, 1H), 3.46–3.38 (m, 2H), 2.87 (t, J=12.6Hz) , 1H), 2.18 (d, J=13.2Hz, 1H), 2.10 (d, J=13.8Hz, 1H), 1.96–1.86 (m, 1H), 1.64–1.56 (m, 1H). ¹³ C NMR( 100MHz, DMSO-d ₆ )δ175.11,163.84,162.04(d,J=8.1Hz),159.56(d,J=8.1Hz),152.25,151.41,150.87,145.61,144.42,131.53(t,J=10.1Hz) ,130.54,121.99,120.15,115.73(t,J＝16.2Hz),112.43(d,J＝6.1Hz),112.24(d,J＝6.1Hz),108.59,72.16,49.87,44.15,41.49,41.26,39.46 , 32.29, 31.86. HRMS calculated for C ₂₅ H ₂₁ F ₂ N ₇ O ₄ S[M+Na] ⁺ 576.1236. Found 576.12505.

Formula (3-27): white solid, yield 66%, mp 155-157°C, ¹ H NMR (600 MHz, CDCl ₃ ) δ 8.67 (dd, J=8.4, 1.6 Hz, 1H), 8.57 (dd, J =4.8,1.6Hz,1H),7.66(s,1H),7.33–7.27(m,2H),6.92(t,J=8.4Hz,2H),6.08(dd,J=12.0,9.0Hz,1H) ,5.46(s,2H),4.60(d,J＝13.8Hz,1H),4.07(d,J＝13.8Hz,1H),3.88–3.73(m,2H),3.63(dd,J＝17.4,9.0 Hz, 1H), 3.39–3.35 (m, 1H), 2.91 (t, J=12.0Hz, 1H), 2.27 (d, J=13.2Hz, 1H), 2.18 (d, J=13.2Hz, 1H), 1.98–1.86 (m, 2H). ¹³ CNMR (100MHz, CDCl ₃ ) δ 174.28, 164.46, 162.49 (d, J=8.1 Hz), 159.99 (d, J=8.1 Hz), 152.15, 151.53, 149.43, 145.01, 132.20 HRMS calculated value C ₂₆ H ₂₁ F ₂ N ₇ O ₂ S[M+H] ⁺ 566.21443. Found 566.21471.

Formula (3-28): white solid, yield 83%, mp 123-124°C, ¹ H NMR (600 MHz, CDCl ₃ ) δ 8.58 (d, J=4.8 Hz, 1H), 7.99 (d, J=8.4 Hz,1H),7.68(s,1H),7.33-7.28(m,1H),7.22(dd,J=8.4,4.8Hz,1H),6.92(t,J=8.4Hz,2H),6.09(dd , J＝12.0, 9.0Hz, 1H), 5.43(s, 2H), 4.59(d, J＝13.7Hz, 1H), 4.04(d, J＝13.8Hz, 1H), 3.82(dd, J＝17.4, 12.0Hz, 1H), 3.64(dd, J＝17.4, 9.0Hz, 1H), 3.34(t, J＝12.0Hz, 2H), 2.87(t, J＝12.6Hz, 1H), 2.28(d, J＝ 12.8Hz, 1H), 2.17 (d, J=13.6Hz, 1H), 1.90 (q, J=12.6Hz, 1H), 1.80 (q, J=12.6Hz, 1H); ¹³ C NMR (150MHz, CDCl ₃ )δ174.14,164.21,161.82(d,J=7.6Hz),160.15(d,J=7.6Hz),152.00,151.07,149.87(d,J=7.6Hz),144.74,130.38(d,J=10.6Hz) ,129.34,119.82,117.87,117.49,115.79,115.38(d,J＝15.2Hz),111.65(d,J＝4.5Hz),111.51(d,J＝4.5Hz),72.52,48.31,44.28,41.64,41.20 , 39.88, 32.13, 31.48. HRMS calculated for C ₂₅ H ₂₁ BrF ₂ N ₆ O ₂ S[M+Na] ⁺ 609.04904. Found 609.04743.

Formula (3-29): white solid, yield 53%, mp120-121°C, ¹ H NMR (600MHz, CDCl ₃ )δ 8.53(s, 1H), 8.10(s, 1H), 8.09(d, J =10.8Hz,1H),7.66(s,1H),7.33–7.25(m,1H),7.14(dd,J=8.4,4.8Hz,1H),6.91(t,J=8.4Hz,2H),6.07 (t, J＝10.6Hz, 1H), 5.44(s, 2H), 4.60(d, J＝13.8Hz, 1H), 4.07(d, J＝13.8Hz, 1H), 3.80(dd, J＝17.2, 12.0Hz, 1H), 3.63(dd, J＝17.2, 9.0Hz, 1H), 3.32(t, J＝12.0Hz, 2H), 2.85(t, J＝12.6Hz, 1H), 2.23(d, J＝ 13.8Hz, 1H), 2.15 (d, J=13.8Hz, 1H), 1.90–1.81 (m, 2H). ¹³ C NMR (100MHz, CDCl ₃ ) δ 174.21, 164.78, 162.31 (d, J=8.1Hz), 159.81(d, J＝8.1Hz), 152.05, 150.59, 148.56, 144.83, 132.85, 130.40(t, J＝11.1Hz), 130.20, 117.81, 116.81, 115.48, 115.47(t, J＝16.2Hz), 111.72( d, J=5.1Hz), 111.53 (d, J=5.1Hz), 72.59 (t, J=3.0Hz), 48.24, 44.37, 41.66, 41.27, 40.00, 32.22, 31.56. HRMS calculated value C ₂₅ H ₂₂ F ₂ N ₆ O ₂ S[M+H] ⁺ 509.15658. Found 509.15668.

Formula (3-30): white solid, yield 82%; mp 110-111°C. ¹ H NMR (600MHz, DMSO-d6) δ 8.40(d, J=5.4Hz, 1H), 8.21(s, 1H) ,8.04(s,1H),7.55(d,J＝4.8Hz,1H),7.53-7.46(m,1H),7.17(t,J＝8.4Hz,2H),6.01(dd,J＝12.0,8.4 Hz,1H),5.58(d,J＝16.8Hz,1H),5.50(d,J＝16.8Hz,1H),4.33(d,J＝13.2Hz,1H),4.13(d,J＝13.2Hz, 1H), 3.91(dd, J＝17.2, 12.0Hz, 1H), 3.55(dd, J＝17.2, 8.4Hz, 1H), 3.45-3.35(m, 2H), 2.83(t, J＝12.6Hz, 1H) ), 2.15(d, J=13.2Hz, 1H), 2.09(d, J=13.2Hz, 1H), 1.88-1.80(m, 1H), 1.57(d, J=12.0Hz, 1H). ¹³ C NMR (150MHz,CDCl ₃ )δ174.16,164.58,162.13,160.51,152.21,151.11,148.95,145.16,132.98,130.52,126.80,120.24,117.75,111.90,111.75,72.83,48.81,44.62,41.94,41.52,40.21,32.44, 31.73. HRMS calculated for C ₂₅ H ₂₁ BrF ₂ N ₆ O ₂ S[M+Na] ⁺ 609.04904, found 609.04777.

Formula (3-31): white solid, yield 89%; mp 143-144°C. ¹ H NMR (600MHz, DMSO-d ₆ ) δ 8.62(s, 1H), 8.56(s, 1H), 8.17(s ,1H),8.04(s,1H),7.55-7.45(m,1H),7.17(t,J=8.4Hz,2H),6.02(dd,J=12.0,8.4Hz,1H),5.57(d, J=16.8, 1H), 5.47 (d, J=16.8, 1H), 4.33 (d, J=13.2Hz, 1H), 4.13 (d, J=13.2Hz, 1H), 3.91 (dd, J=17.4, 12.0Hz, 1H), 3.55(dd, J=17.4, 8.4Hz, 1H), 3.47-3.35(m, 1H), 3.34-3.26(m, 1H), 2.83(t, J=12.6Hz, 1H), 2.15 (d, J=13.2Hz, 1H), 2.09 (d, J=13.2Hz, 1H), 1.90-1.75 (m, 1H), 1.65-1.50 (m, 1H). ¹³ C NMR (100MHz, DMSO) δ175.12,164.77,162.03(d,J＝8.0),159.56(d,J＝8.0),152.25,149.07,144.41,132.58,132.21,131.54(t,J＝10.0),120.12,116.93,115.74(d,J =16.2), 112.43(d, J=5.0), 112.25(d, J=5.0), 112.00, 72.16, 48.72, 44.05, 41.36, 41.27, 32.37, 31.90. HRMS calculated values C ₂₅ H ₂₁ BrF ₂ N ₆ O ₂ S[M+Na] ⁺ 609.04904, found 609.04935.

Formula (3-32): white solid, yield 92%; mp 165-166°C. ¹ H NMR (600 MHz, DMSO-d ₆ ) δ 8.23 (d, J=4.8 Hz, 1H), 8.22 (s, 1H ),8.05(d,J＝3.6Hz,1H),7.55-7.48(m,1H),7.43(d,J＝8.4Hz,1H),7.17(t,J＝8.4Hz,2H),6.02(t , J＝10.8Hz, 1H), 5.54(d, J＝16.8Hz, 1H), 5.45(d, J＝16.8Hz, 1H), 4.35(d, J＝13.2Hz, 1H), 4.14(d, J =13.2Hz,1H),4.06-3.98(m,1H),3.92(dd,J=17.4,12.0Hz,1H),3.55(dd,J=17.4,8.4Hz,1H),3.44-3.39(m, 1H), 2.85(t, J＝13.2Hz, 1H), 2.16(d, J＝13.2Hz, 1H), 2.10(d, J＝13.2Hz, 1H), 1.94-1.82(m, 1H), 1.68- 1.57(m,1H) ^.13C NMR(100MHz,DMSO)δ175.05,164.70,161.99(d,J=8.0),159.51(d,J=8.0),152.22,150.34,144.36,140.62,133.42,133.20,131.46 (t, J=10.0), 120.76, 119.96, 115.68 (t, J=16.2), 114.39, 112.37 (d, J=5.0), 112.17 (d, J=5.0), 72.11, 48.62, 44.03, 41.33, 41.24 , 32.33, 31.81. HRMS calculated for C ₂₅ H ₂₁ BrF ₂ N ₆ O ₂ S[M+Na] ⁺ 609.04904, found 609.04888.

Formula (3-33): white solid, yield 86%; mp 87-88°C. ¹ H NMR (600 MHz, CDCl ₃ ) δ 8.67 (d, J=8.4, 1H), 8.57 (d, J=4.8, 1H), 7.66(s, 1H), 7.33-7.27(m, 2H), 6.92(t, J=8.4Hz, 2H), 6.08(dd, J=12.0, 9.6Hz, 1H), 5.46(s, 2H) ), 4.60(d, J=13.2Hz, 1H), 4.07(d, J=13.2Hz, 1H), 3.88-3.73(m, 2H), 3.66-3.60(m, 1H), 3.39-3.35(m, 1H), 2.93-2.87(m, 1H), 2.27(d, J=13.2Hz, 1H), 2.18(d, J=13.2Hz, 1H), 1.98-1.86(m, 2H). ¹³ C NMR(100MHz) ,CDCl ₃ )δ174.28,164.46,162.52,162.45,160.02,159.95,152.15,151.53,149.43,145.01,132.20,130.68,130.57,130.47,118.97,118.05,115.75,115.59,115.43,114.79,111.93,111.69,72.79, 48.80, 44.70, 41.99, 41.41, 40.09, 32.36, 31.71. HRMS calculated for C ₂₆ H ₂₁ F ₅ N ₆ O ₂ S[M+Na] ⁺ 599.12591, found 599.12602.

Formula (3-34): white solid, yield 92%; mp 154-155°C. ¹ H NMR (600 MHz, DMSO-d ₆ ) δ 8.91(s, 1H), 8.79(s, 1H), 8.39(s ,1H),8.06(s,1H),7.55-7.46(m,1H),7.18(t,J=8.4Hz,2H),6.03(dd,J=12.0,8.4Hz,1H),5.67(d, J=16.8, 1H), 5.58 (d, J=16.8, 1H), 4.35 (d, J=13.2Hz, 1H), 4.16 (d, J=13.2Hz, 1H), 3.93 (dd, J=17.2, 12.0Hz,1H),3.46-3.38(m,1H),3.37-3.33(t,J=12.6Hz,2H),2.84(t,J=12.0Hz,1H),2.17(d,J=13.2Hz, 1H), 2.10(d, J=13.2Hz, 1H), 1.91-1.85(m, 1H), 1.61-1.55(m, 1H). ¹³ C NMR(100MHz, CDCl ₃ )δ174.14,164.46,162.59(d, J=8.0), 160.09 (d, J=8.0), 152.21, 151.81, 145.93 (t, J=3.0), 134.80, 134.08, 130.56 (t, J=10.0), 128.44 (q, J=4.0), 124.16 (q, J=135.0), 120.37 (q, J=33.0), 117.80, 115.72 (t, J=16.2), 114.45, 111.94 (d, J=6.0), 111.75 (d, J=6.0), 72.86 ( t, J＝3.0), 48.69, 44.65, 42.00, 41.52, 41.49, 40.21, 32.47, 31.73. HRMS calculated value C ₂₆ H ₂₁ F ₅ N ₆ O ₂ S[M+Na] ⁺ 599.12591, measured value 599.12565.

Formula (3-35): white solid, yield 78%; mp 128-129°C. ¹ H NMR (600MHz, DMSO-d ₆ ) δ 8.61 (d, J=8.4Hz, 1H), 8.42 (s, 1H) ), 8.06(s, 1H), 7.73(d, J=8.4Hz, 1H), 7.53-7.49(m, 1H), 7.17(t, J=8.4Hz, 2H), 6.01(t, J=10.8Hz) ,1H),5.65(d,J＝16.8Hz,1H),5.55(d,J＝16.8Hz,1H),4.34(d,J＝13.2Hz,1H),4.18(d,J＝13.2Hz,1H) ), 3.93-3.88(m, 1H), 3.57-3.52(m, 1H), 3.45-3.39(m, 1H), 3.34(s, 1H), 2.85(t, J=13.2Hz, 1H), 2.17( d, J=9.6Hz, 1H), 2.11 (d, J=9.6Hz, 1H), 1.65-1.50 (m, 2H). ¹³ C NMR (150MHz, CDCl ₃ ) δ 174.20, 164.69, 162.20, 160.53, 152.29, 149.99,145.16,133.27,133.10,131.88,130.54,117.81,117.28,113.25,111.92,111.76,72.85,48.24,44.76,42.00,41.54,40.24,36.80,32.47,31.75,20.34.HRMS计算值C ₂₆ H ₂₁ F ₅ N ₆ O ₂ S[M+Na] ⁺ 599.12591, found 599.12762.

Formula (3-36): white solid, yield 84%; mp 161-163°C. ¹ H NMR (400 MHz, CDCl ₃ ) δ 9.99 (s, 1H), 8.58-8.44 (m, 1H), 8.38-8.25 (m, 1H), 8.04 (d, J=4.0Hz, 1H), 7.64 (d, J=4.0Hz, 1H), 7.50–7.46 (m, 1H), 7.38–7.30 (m, 2H), 6.29 ( td, J=11.6, 4.0Hz, 1H), 5.28 (s, 2H), 4.60 (d, J=13.2Hz, 1H), 4.15 (d, J=13.6Hz, 1H), 3.84 (ddd, J=16.8 ,12.0,4.0Hz,1H),3.66(ddd,J=16.4,10.4,4.0Hz,1H),3.37(q,J=12.4,11.2Hz,2H),3.25(d,J=4.0Hz,3H) ,2.91(t,J＝13.2Hz,1H),2.29(d,J＝13.2Hz,1H),2.19-2.13(m,1H),1.95-1.85(m,1H),1.81-1.76(m,1H) ). ¹³ C NMR(100MHz,CDCl ₃ )δ185.03,174.34,164.78,152.89,148.63,148.36,145.00,144.76,140.09,135.25,130.94,130.29,129.73,129.14,121.26,119.10,118.45,117.44,116.95,45.33 , 44.90, 42.15, 41.91, 40.19, 37.99, 32.48, 31.79. HRMS (ESI) calculated for C ₂₇ H ₂₅ ClN ₆ O ₆ S ₂ [M+Na] ⁺ : 651.0858, found 651.0832.

Formula (3-37): white solid, yield 83%; mp 157-158°C. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.52 (t, J=3.6 Hz, 1H), 8.04 (d, J=8.8 Hz, 1H), 7.66 (d, J=3.2Hz, 1H), 7.57–7.49 (m, 1H), 7.46–7.29 (m, 2H), 7.12 (dt, J=8.0, 3.6Hz, 1H), 6.37 –6.22(m,1H),5.39(d,J＝3.2Hz,2H),4.63(d,J＝13.2Hz,1H),4.09(d,J＝13.6Hz,1H),3.86(ddd,J＝ 16.4,12.4,3.2Hz,1H),3.67(ddd,J=17.2,11.2,3.2Hz,1H),3.40–3.30(m,2H),3.25(d,J=3.2Hz,3H),2.87(t , J=12.8Hz, 1H), 2.61 (d, J=3.2Hz, 3H), 2.22 (q, J=14.0, 13.2Hz, 2H), 1.82 (dt, J=24.4, 12.8Hz, 2H). ¹³ C NMR(100MHz,CDCl ₃ )174.61,165.27,152.96,151.60,148.70,144.95,141.87,135.22,130.19,129.82,128.99,121.24,118.22,116.19,115.57,48.17,44.64,42.00,41.95,40.35,38.02, 32.51, 32.45, 31.86, 31.80, 29.67, 12.55. HRMS (ESI) calculated for C ₂₇ H ₂₇ ClN ₆ O ₅ S ₂ [M+Na] ⁺ : 637.1065, found 637.1062.

Formula (3-38): white solid, yield 75%; mp 148-150°C. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.67 (d, J=4.4 Hz, 1H), 8.24 (d, J=8.0 Hz, 1H), 7.68(s, 1H), 7.52(d, J=8.0Hz, 1H), 7.44–7.27(m, 3H), 6.31(t, J=11.6Hz, 1H), 5.54(s, 2H) ),4.61(d,J＝13.6Hz,1H),4.08(d,J＝13.6Hz,1H),3.88(dd,J＝17.2,12.4Hz,1H),3.68(dd,J＝17.2,10.8Hz ,1H),3.40(td,J＝12.4,10.8,4.8Hz,2H),3.27(s,3H),2.92(t,J＝12.8Hz,1H),2.32(d,J＝13.2Hz,1H) , 2.21 (d, J=11.2Hz, 1H), 1.96 (d, J=12.0Hz, 1H), 1.84 (q, J=12.4, 11.6Hz, 1H). ¹³ C NMR (100MHz, CDCl ₃ ) 174.36, 163.99,152.96,151.15,150.20,148.71,145.01,135.24,133.87(q,J＝39.3Hz),130.21,129.74,129.61,129.02,125.29,122.61,121.24,119.93,118.91,118.25,117.26,112.41,49.02, 44.69, 42.01, 40.24, 38.01, 32.44 (d, J=5.6 Hz), 31.78 (d, J=5.1 Hz). HRMS (ESI) calculated for C ₂₇ H ₂₄ ClF ₃ N ₆ O ₅ S ₂ [M+Na ] ⁺ :691.0782, the measured value is 691.0794.

Formula (3-39): white solid, yield 83%; mp 177-179°C. ¹ H NMR (600 MHz, CDCl ₃ ) δ 8.50 (d, J=4.8 Hz, 1H), 8.07 (d, J=7.8 Hz, 1H), 7.63(s, 1H), 7.50(d, J=8.4Hz, 1H), 7.39(d, J=8.4Hz, 1H), 7.33(t, J=8.4Hz, 1H), 7.11( dd,J＝7.8,4.8Hz,1H),6.28(t,J＝11.4Hz,1H),5.41(s,2H),4.60(d,J＝14.4Hz,1H),4.06(d,J＝14.4 Hz,1H),3.83(dd,J=17.2,12.0Hz,1H),3.64(dd,J=17.2,10.8Hz,1H),3.34–3.28(m,2H),3.22(s,3H),2.95 (t, J=7.6Hz, 2H), 2.85 (t, J=12.6Hz, 1H), 2.22 (d, J=12.6Hz, 1H), 2.15 (d, J=15.0Hz, 1H), 1.84 (q , J=7.2Hz, 4H), 1.00 (t, J=7.2Hz, 3H). ¹³ C NMR (100MHz, CDCl ₃ )δ182.13, 174.69, 165.25, 152.99, 151.56, 148.70, 148.53, 146.04, 144.93, 135.25, 130.23, 129.73, 129.02, 121.27, _118.28 , _116.17 , _115.15 , 66.83, 59.08, 48.32, 44.67, 42.00, 40.38, 38.00, 32.45, 31.88, 29.66, 22.46, 14.08 Calcd O ₅ S ₂ [M+Na] ⁺ : 665.1378, found 665.1383.

Formula (3-40): white solid, yield 80%; mp 181-183°C. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.55-8.39 (m, 1H), 8.23-8.11 (m, 1H), 7.66 (d, J=5.6Hz, 1H), 7.52–7.49 (m, 1H), 7.44–7.33 (m, 2H), 7.09 (m, 1H), 6.37–6.20 (m, 1H), 5.39 (t, J =4.8Hz,2H),4.64(d,J=13.6Hz,1H),4.11(d,J=13.6Hz,1H),3.86–3.72(m,1H),3.67–3.51(m,1H),3.39 –3.29(m,2H),3.25(d,J=5.6Hz,3H),2.85-2.74(m,1H),2.20(q,J=13.2,9.6Hz,2H),1.83-1.71(m,2H) _The ^_ , 121.28, 118.28, 117.25, 115.79, 113.49, 59.40, 48.45, 44.75, 42.00, 41.28, 40.39, 38.01, 34.20, 32.43, 31.90, 30.08.HRMS (ESI) Calculated C ₃₀ H ₃₃ ClN ₆ O ₅ S ₂ M+Na] ⁺ : 679.1535, the measured value is 679.1537.

Formula (3-41): white solid, yield 46%; mp 170-172°C. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.56 (d, J=7.2 Hz, 1H), 8.46 (d, J=4.4 Hz, 1H), 7.81(s, 1H), 7.43–7.34(m, 2H), 6.84(t, J=8.0Hz, 2H), 6.13(dd, J=12.4, 9.2Hz, 1H), 5.64(s) ,2H),4.71(d,J＝13.2Hz,1H),4.22(d,J＝13.2Hz,1H),3.83(dd,J＝17.6,12.4Hz,1H),3.71(dd,J＝17.6, 9.2Hz, 1H), 3.61–3.32 (m, 2H), 3.27 (s, 3H), 2.91–2.73 (m, 1H), 2.67 (s, 3H), 2.45 (d, J=12.0Hz, 1H), 2.23(d, J=12.0Hz, 1H), 2.14-1.80(m, 2H). ¹³ C NMR (100MHz, CDCl ₃ )δ190.42, 176.33, 165.45, 163.25, 161.81, 154.25, 153.60, 150.24, 146.11, 142.07, 134.37, 131.16 (t, J=7.2Hz), 121.51, 118.56, 116.35 (t, J=10.7Hz), 114.58, 112.30, 111.79, 73.06, 50.49, 45.78, 42.15, 41.87, 40.83, 37.5, 34.59, 32.50 28.38.

Formula (3-42): white solid, yield 78%; mp 166-168°C. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.74 (d, J=4.0 Hz, 1H), 7.76 (d, J=8.4 Hz, 1H), 7.69(s, 1H), 7.29–7.04(m, 2H), 6.99(dd, J=16.8, 10.4Hz, 1H), 6.89(t, J=8.0Hz, 2H), 6.72(d , J＝16.8Hz, 1H), 6.32(dd, J＝12.0, 9.2Hz, 1H), 5.68(d, J＝11.2Hz, 1H), 5.33(d, J＝4.0Hz, 2H), 4.57(d , J=13.5Hz, 1H), 4.13 (d, J=13.9Hz, 1H), 3.72 (dd, J=17.1, 12.0Hz, 1H), 3.57 (dd, J=17.1, 9.2Hz, 1H), 3.41 ^13C NMR (100MHz, CDCl ₃ ) δ 175.44, 166.75, 163.70 (d, J=8.4 Hz), 161.18 (d, J=8.4 Hz), 155.31, 152.82, 149.92, 146.21, 142.95, 131.54 (t, J=10.0 Hz) ,130.67,129.48,117.91,117.67,117.35,115.84(t,J=17.6Hz),114.02,111.26(d,J=7.2Hz),111.03(t,J=7.2Hz),72.23(t,J=4.2 Hz), 50.39, 46.72, 42.87, 42.60, 40.64, 38.09, 33.89, 31.99.

Formula (3-43): white solid, yield 52%; mp 180-182°C. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.62 (d, J=4.4 Hz, 1H), 8.21 (d, J=8.4 Hz, 1H), 7.74 (s, 1H), 7.53–7.43 (m, 1H), 7.28–7.19 (m, 1H), 6.98 (t, J=8.4Hz, 2H), 6.26–6.06 (m, 1H) ,5.50(s,2H),4.61(d,J＝12.8Hz,1H),4.11(d,J＝12.8Hz,1H),3.90–3.75(dd,J＝17.6,8.4Hz,1H),3.66( dd, J=17.6, 8.8Hz, 1H), 3.60 (s, 3H), 3.49 (s, 1H), 3.35–3.16 (m, 2H), 2.92 (t, J=12.0Hz, 1H), 2.34–2.19 (m, 2H), 1.98–1.78 (m, 2H). ¹³ C NMR (100 MHz, CDCl ₃ ) δ 175.33, 166.74, 163.87 (d, J=7.2 Hz), 161.25 (d, J=7.2 Hz), 155.42, 151.69, 150.13, 146.15, 131.69(t, J=11.9Hz), 130.02, 128.51, 118.91, 118.80, 117.65, 116.31(t, J=15.8Hz), 112.05(d, J=5.7Hz), 111.84(d, J=5.7Hz), 83.48, 75.80, 72.97, 50.15, 46.82, 43.21, 41.87, 40.47, 38.11, 33.02, 32.19.

Formula (3-44): white solid, yield 70%; mp 178-179°C. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.72 (dd, J=4.4, 1.6 Hz, 1H), 8.64 (dd, J =8.4,1.6Hz,1H),7.68(s,1H),7.51(dt,J=8.4,5.6Hz,2H),7.45–7.34(m,2H),6.32(dd,J=12.0,10.4Hz, 1H), 5.62 (d, J=2.0Hz, 2H), 4.64–4.56 (m, 1H), 4.08 (d, J=13.6Hz, 1H), 3.89 (dd, J=17.2, 12.4Hz, 1H), 3.69(dd,J＝17.2,10.8Hz,1H),3.49-3.37(m,2H),3.28(s,3H),2.95(t,J＝13.2Hz,1H),2.37(d,J＝13.2Hz , 1H), 2.22(d, J＝12.8Hz, 1H), 2.04-1.98(m, 1H), 1.86(dd, J＝13.6, 9.6Hz, 1H). ¹³ C NMR (100MHz, CDCl ₃ )δ178. 65,165.62,157.58,153.78,151.45,147.88,142.26,137.64,135.57,134.25,133.79,132.08,128.06,127.52,124.36,122.97,118.88,115.72,106.51,56.64,49.63,45.47,43.76,37.24,33.68,32.74. HRMS (ESI) calculated for C ₂₆ H ₂₄ ClN ₇ O ₇ S ₂ [M+Na] ⁺ : 630.1779, found 630.1792.

Formula (3-45): white solid, yield 48%; mp 182-184°C. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.66 (dd, J=4.6, 1.4 Hz, 1H), 8.23 (dd, J =8.1,1.5Hz,1H),7.65(s,1H),7.50(dd,J=8.0,1.4Hz,1H),7.43–7.31(m,3H),6.29(dd,J=12.2,10.6Hz, 1H), 5.52(s, 2H), 4.57(d, J=13.6Hz, 1H), 4.04(d, J=13.8Hz, 1H), 3.85(dd, J=17.3, 12.2Hz, 1H), 3.65( dd, J=17.3, 10.6Hz, 1H), 3.39 (qd, J=11.7, 11.2, 3.3Hz, 2H), 3.23 (s, 3H), 2.98–2.84 (m, 1H), 2.37–2.29 (m, 1H), 2.24–2.16 (m, 1H), 1.96 (q, J=12.0Hz, 1H), 1.83 (qd, J=12.0, 4.1Hz, 1H). ¹³ C NMR (100MHz, CDCl ₃ )δ174.23, 163.62 ,152.94,150.66,148.71,145.04,135.26,130.24,129.73,129.15,129.05,121.25,119.69,118.30,117.93,117.04,112.78,49.35,44.73,42.05(d,J＝11.4Hz),40.19,37.99,32.45 (d, J=5.0Hz), 31.73 (d, J=5.0Hz).

Formula (3-46): white solid, yield 77%; mp 169-171°C. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.59 (d, J=4.4 Hz, 1H), 8.00 (d, J=8.0 Hz,1H),7.66(s,1H),7.51(d,J＝8.0Hz,1H),7.38(dt,J＝16.0,8.0Hz,2H),7.23(dd,J＝8.0,4.4Hz,1H) ),6.30(t,J＝11.2Hz,1H),5.43(s,2H),4.60(d,J＝13.2Hz,1H),4.06(d,J＝13.6Hz,1H),3.86(dd,J =17.2,12.4Hz,1H),3.67(dd,J=17.2,10.4Hz,1H),3.36(t,J=12.0Hz,2H),3.26(s,3H),2.89(t,J=12.4Hz , 1H), 2.29 (d, J=13.2Hz, 1H), 2.18 (d, J=10.4Hz, 1H), 1.84 (dt, J=38.8, 13.2Hz, 2H). ¹³ C NMR (150MHz, CDCl ₃ )δ170.91,160.88,149.35,147.79,146.53,145.08,141.36,131.64,126.64,126.27,126.14,125.45,117.66,116.79,114.75,114.18,112.71,45.11,41.22–40.88(m),38.41,36.68,34.45, 28.88 (d, J=8.5 Hz), 28.21 (d, J=7.4 Hz). HRMS (ESI) calculated for C ₂₆ H ₂₄ BrClN ₆ O ₅ S ₂ [M+Na] ⁺ : 701.0014, found 701.0015.

Formula (3-47): white solid, yield 75%; mp 160-162°C. ¹ H NMR (600 MHz, CDCl ₃ ) δ 8.53 (dd, J=4.8, 1.5 Hz, 1H), 8.09 (d, J ＝7.2Hz, 2H), 7.62(s, 1H), 7.49(d, J＝8.2Hz, 1H), 7.38(d, J＝8.0Hz, 1H), 7.33(t, J＝8.2Hz, 1H), 7.15(dd,J＝8.0,4.5Hz,1H),6.27(dd,J＝12.2,10.6Hz,1H),5.44(s,2H),4.60(d,J＝13.6Hz,1H),4.06(d , J=13.8Hz, 1H), 3.83 (dd, J=17.2, 12.2Hz, 1H), 3.63 (dd, J=17.2, 10.6Hz, 1H), 3.32 (tt, J=11.1, 3.4Hz, 2H) ,3.22(s,3H),2.89–2.82(m,1H),2.24(d,J=13.4Hz,1H),2.15(d,J=13.4Hz,1H),1.88–1.74(m,2H). ¹³ C NMR(150MHz,CDCl ₃ )δ174.53,164.95,152.93,150.77,148.76,148.64,144.90,135.20,133.17,130.49,130.17,129.67,128.97,121.21,118.22,117.04,115.78,48.49,44.64,41.94,40.31 ,37.93,32.46(d,J=9.9Hz),31.78(d,J=9.8Hz).

Formula (3-48): white solid, yield 70%; mp 166-168°C. ¹ H NMR (600MHz, CDCl ₃ ) δ 8.31(d, J=4.8Hz, 1H), 8.10(s, 1H), 7.63(s, 1H), 7.49(d, J=8.2Hz, 1H), 7.38(d, J=8.1Hz, 1H), 7.33(dd, J=9.3, 6.6Hz, 2H), 6.30–6.24(m ,1H),5.41(s,2H),4.59(d,J＝13.6Hz,1H),4.04(d,J＝13.8Hz,1H),3.83(dd,J＝17.3,12.2Hz,1H),3.64 (dd, J=17.2, 10.6Hz, 1H), 3.36–3.29 (m, 2H), 3.22 (s, 3H), 2.90–2.83 (m, 1H), 2.26 (d, J=13.6Hz, 1H), 2.16(d, J=13.6Hz, 1H), 1.88(t, J=12.4Hz, 1H), 1.78(s, 1H). ¹³ C NMR (150MHz, CDCl ₃ )δ174.38, 164.57, 152.91, 151.13, 148.98, 148.64,144.93,135.20,133.04,130.18,129.67,128.98,126.83,121.21,120.27,118.23,117.77,48.82,44.63,41.94,40.25,37.93,32.48,1.7.81,32.48,1.7.81

Formula (3-49): white solid, yield 65%; mp 171-173°C. ¹ H NMR (600 MHz, CDCl ₃ ) δ 8.53 (d, J=2.1 Hz, 1H), 8.20 (d, J=2.1 Hz, 1H), 8.03(s, 1H), 7.62(s, 1H), 7.48(d, J=8.2Hz, 1H), 7.38(d, J=8.1Hz, 1H), 7.32(t, J=8.2 Hz,1H),6.29–6.23(m,1H),5.39(s,2H),4.57(d,J=13.6Hz,1H),4.03(d,J=13.7Hz,1H),3.82(dd,J =17.3,12.2Hz,1H),3.63(dd,J=17.3,10.6Hz,1H),3.32(tt,J=11.5,3.6Hz,2H),3.21(s,3H),2.89–2.81(m, 1H), 2.25 (d, J=13.4Hz, 1H), 2.15 (d, J=13.4Hz, 1H), 1.86 (dd, J=12.0, 6.5Hz, 1H), 1.77 (tt, J=12.5, 6.6 Hz,1H). ¹³ C NMR(150MHz,CDCl ₃ )δ170.47,160.66,148.95,145.78,145.44,144.70,140.97,131.26,128.43,128.15,126.24,125.72,125.05,117.26,114.30,113.18,108.80,44.69, 40.75, 40.67, 38.00, 36.31, 36.25, 34.02, 33.96.

Formula (3-50): white solid, yield 63%; mp163-165°C. ¹ H NMR (600MHz, CDCl ₃ ) δ 8.41(d, J=4.8Hz, 1H), 8.23(s, 1H), 7.52(s, 1H), 7.50(d, J=8.4Hz, 1H), 7.41(d, J=8.4Hz, 1H), 7.35(dd, J=9.0, 6.6Hz, 2H), 6.53–6.31(m ,1H),5.54(s,2H),4.69(d,J＝13.8Hz,1H),4.23(d,J＝13.8Hz,1H),3.61(dd,J＝17.4,12.6Hz,1H),3.60 (dd, J=17.4, 10.8Hz, 1H), 3.42–3.30 (m, 2H), 3.31 (s, 3H), 2.99–2.75 (m, 1H), 2.33 (d, J=13.8Hz, 1H), 2.21(d, J=13.7Hz, 1H), 1.76(t, J=12.8Hz, 1H), 1.73(s, 1H). ¹³ C NMR (150MHz, CDCl ₃ )δ 176.44, 166.37, 153.81, 152.16, 149.68, 148.56,145.67,136.62,134.26,132.31,130.74,129.51,126.66,123.31,121.19,118.57,118.03,50.62,45.33,42.48,41.37,38.06,33.62,1.2.19.32

Formula (3-51): white solid, yield 62%; mp 163-165°C. ¹ H NMR (600MHz, CDCl ₃ ) δ 8.45(d, J=4.8Hz, 1H), 8.23(s, 1H), 7.74(s, 1H), 7.53(d, J=8.4Hz, 1H), 7.41(d, J=8.0Hz, 1H), 7.31(dd, J=9.6, 6.0Hz, 2H), 6.53–6.48(m ,1H),5.62(s,2H),4.71(d,J＝12.6Hz,1H),4.32(d,J＝12.8Hz,1H),4.03(dd,J＝17.4,12.0Hz,1H),3.76 (dd, J=17.4, 10.4Hz, 1H), 3.40–3.34 (m, 2H), 3.25 (s, 3H), 2.99–2.92 (m, 1H), 2.38 (d, J=13.8Hz, 1H), 2.20(d, J=13.8Hz, 1H), 1.90(t, J=12.6Hz, 1H), 1.81(s, 1H). ¹³ C NMR (150MHz, CDCl ₃ )δ174.40, 166.62, 154.81, 152.06, 149.11, 148.76, 145.86, 137.61, 134.63, 131.20, 130.29, 129.05, 127.74, 122.38, 121.37, 119.64, 118.58, 50.31, 46.52, 43.71, 41.52, 39.26, 34.27, 1.74.20

Formula (3-52): white solid, yield 81%; mp 167-169°C. ¹ H NMR (400MHz, CDCl ₃ ) δ 8.69(d, J=2.4Hz, 1H), 8.30(s, 1H), 8.14 (d, J=2.4Hz, 1H), 7.56 (d, J=2.4Hz, 1H), 7.41 (d, J=8.0Hz, 1H), 7.32–7.23 (m, 2H), 6.26–6.11 (m ,1H),5.40(d,J＝2.4Hz,2H),4.50(d,J＝13.6Hz,1H),3.99(d,J＝13.6Hz,1H),3.82–3.70(m,1H),3.57 (ddd, J=17.2, 10.8, 2.4Hz, 1H), 3.28 (q, J=11.2, 10.0Hz, 2H), 3.15 (d, J=2.4Hz, 3H), 2.81 (t, J=12.8Hz, 1H), 2.22(d, J=13.2Hz, 1H), 2.13–2.04(m, 1H), 1.84(d, J=11.6Hz, 1H), 1.73(d, J=12.4Hz, 1H). ¹³ CNMR (100MHz,CDCl ₃ )δ205.86,174.43,164.52,152.95,151.85,148.69,145.99,145.00,135.26,134.13,130.26,129.74,129.07,128.52,122.87,121.27,120.44(q,J＝32.6Hz),118.35, 114.51, 66.96, 48.73, 44.70, 41.98, 40.27, 38.00, 32.47, 31.80. HRMS (ESI) calculated for C ₂₇ H ₂₄ ClF ₃ N ₆ O ₅ S ₂ [M+Na] ⁺ : 691.0782, found 691.0781.

Formula (3-53): white solid, yield 81%; mp 171-173°C. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.35-8.21 (m, 2H), 7.68 (q, J=3.6 Hz, 1H) ), 7.58–7.53 (m, 2H), 7.45–7.36 (m, 2H), 6.36–6.27 (m, 1H), 5.52 (d, J=3.6Hz, 2H), 4.63 (d, J=13.2Hz, 1H), 4.14 (d, J=13.6Hz, 1H), 3.89 (ddd, J=16.8, 12.4, 3.6Hz, 1H), 3.69 (ddd, J=17.2, 10.8, 3.6Hz, 1H), 3.48–3.34 (m, 2H), 3.28 (d, J=4.0Hz, 3H), 3.00–2.86 (m, 1H), 2.34 (d, J=13.2Hz, 1H), 2.27–2.18 (m, 1H), 2.06– 1.78(m,2H). ¹³ C NMR(100MHz,CDCl ₃ )δ174.52,164.74,152.99,150.05,148.71,146.91,146.54,144.99,135.27,133.36,131.96,130.26,129.74,129.06,121.28,120.32,118.35, 117.36, 113.33, 59.23, 48.29, 44.82, 42.03, 40.33, 38.01, 32.50, 31.84. HRMS (ESI) calculated for C ₂₇ H ₂₄ ClF ₃ N ₆ O ₅ S ₂ [M+Na] ⁺ : 691.0782, found 691.0780 .

Example 4

This example is used to illustrate the preparation method of the compound represented by formula (3-2).

At 0 °C, the compound represented by formula (3-1) (1.87 mmol, 1 eq) was dissolved in 10 mL of anhydrous tetrahydrofuran, NaBH ₄ (2.80 mmol, 1.5 eq) was slowly added, and 3 mL of methanol was slowly added dropwise, and the temperature increased. to room temperature for 1 h. After the reaction was completed, 20 mL of saturated ammonium chloride was added for quenching, 10 mL was added, the reaction system was extracted with ethyl acetate, the organic phase was dried, concentrated, and the compound represented by formula (3-2) was obtained by column chromatography.

Formula (3-2): white solid, yield 95%, mp 168-170°C, ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.51 (dd, J=4.8, 1.6 Hz, 1H), 8.32 (dd , J=8.0, 1.6Hz, 1H), 8.04(s, 1H), 7.50(tt, J=8.4, 6.4Hz, 1H), 7.22(dd, J=8.0, 4.8Hz, 1H), 7.17(t, J=8.4Hz, 2H), 6.56 (s, 1H), 6.07–5.96 (m, 1H), 5.54–5.34 (m, 3H), 4.79 (d, J=5.2Hz, 2H), 4.35 (d, J =13.2Hz,1H),4.15(d,J=13.2Hz,1H),3.92(dd,J=17.2,12.0Hz,1H),3.55(dd,J=17.2,8.4Hz,1H),3.45–3.36 (m, 1H), 2.82 (t, J=11.6Hz, 1H), 2.12 (dd, J=23.6, 12.8Hz, 2H), 1.83 (q, J=10.4, 9.6Hz, 1H), 1.64–1.48 ( m, 1H). ¹³ C NMR (100MHz, DMSO-d ₆ )δ175.11, 165.09, 162.01(d, J=8.1Hz), 159.53(d, J=8.1Hz), 152.23, 151.39, 148.62, 144.64, 144.39, 131.49(t,J＝11.1Hz),130.58,120.05,116.54,115.71(t,J＝16.2Hz),113.97,112.40(d,J＝6.1Hz),112.20(d,J＝6.1Hz),72.13, 59.55, 57.20, 48.90, 48.09, 44.02, 41.28 (d, J=4.0Hz), 32.39, 31.91. HRMS calculated value C ₂₆ H ₂₄ F ₂ N ₆ O ₃ S[M+H] ⁺ 539.16714. Measured value 539.17034.

Example 5

This example is used to illustrate the preparation method of the compound represented by the formula (3-3).

At 0 °C, the compound represented by formula (3-2) (1.00 mmol, 1 eq) was dissolved in 10 mL of anhydrous tetrahydrofuran, sodium hydride (1.50 mmol, 1.5 eq) was slowly added, the reaction was continued for 0.5 hours, and then iodine was added dropwise. Methane (1.20 mmol, 1.2 eq), the reaction was complete. The temperature was raised to room temperature, 10 mL of water was added, the system was extracted with ethyl acetate, the organic phase was dried, concentrated, and the compound represented by formula (3-3) was obtained by column chromatography.

Formula (3-3): white solid, yield 90%, mp 147-149°C, ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.54 (dd, J=4.8, 1.6 Hz, 1H), 8.27 (dd , J=8.0, 1.6Hz, 1H), 8.04(s, 1H), 7.50(tt, J=8.4, 6.4Hz, 1H), 7.25(dd, J=8.0, 4.8Hz, 1H), 7.17(t, J＝8.4Hz, 2H), 6.02(dd, J＝12.0, 8.4Hz, 1H), 5.53(d, J＝16.8Hz, 1H), 5.44(d, J＝16.8Hz, 1H), 4.73(s, 2H), 4.34 (d, J=13.2Hz, 1H), 4.15 (d, J=13.2Hz, 1H), 3.92 (dd, J=17.2, 12.0Hz, 1H), 3.55 (dd, J=17.2, 8.4 Hz, 1H), 3.45–3.36 (m, 1H), 3.31 (s, 3H), 3.27–3.37 (m, 1H), 2.82 (t, J=11.6Hz, 1H), 2.20–2.05 (m, 2H) ,1.90-1.75(m,1H),1.64-1.50(m,1H). ¹³ C NMR(100MHz,DMSO-d ₆ )δ175.11,165.08,161.99(d,J=8.1Hz),159.51(d,J= 8.1Hz), 151.85, 151.33, 148.55, 144.61, 142.54, 131.44 (t, J=11.6Hz), 130.01, 123.11, 116.51, 115.66 (t, J=16.2Hz), 114.00, 112.38 (d, J=6.1Hz) ),112.17(d,J＝6.1Hz),72.09,62.35,58.77,57.14,48.88,48.13,43.98,41.25(d,J＝4.0Hz),32.45,32.03.HRMS calculated value C ₂₇ H ₂₆ F ₂ N ₆ O ₃ S[M+H] ⁺ 553.18279. Found 553.18420.

Example 6

This example is used to illustrate the preparation method of the compound represented by formula (3-4).

At room temperature, the compound represented by formula (3-1) (1.00 mmol, 1 eq) was dissolved in 10 mL of anhydrous dichloromethane, thionyl chloride (5.00 mmol, 5 eq) was slowly added, and the reaction was heated under reflux for 3 h. After the reaction was completed, the reaction system was poured into 20 mL of ice water for quenching, extracted with dichloromethane, the organic phase was dried, concentrated, and the compound represented by formula (3-4) was obtained by column chromatography.

Formula (3-4): white solid, yield 85%, mp142-143°C, ¹ H NMR (400MHz, CDCl ₃ )δ8.56(s, 1H), 8.24(d, J=7.6Hz, 1H), 7.66 (s, 1H), 7.38–7.28 (m, 1H), 7.24–7.13 (m, 1H), 6.92 (t, J=8.4Hz, 2H), 6.08 (t, J=10.2Hz, 1H), 5.43 (s, 2H), 4.95 (s, 2H), 4.59 (d, J=12.6Hz, 1H), 4.05 (d, J=10.8Hz, 1H), 3.81 (dd, J=16.8, 12.0Hz, 1H) ,3.63(dd,J=16.8,9.6Hz,1H),3.45-3.20(m,2H),2.87(t,J=12.0Hz,1H),2.34-2.12(m,2H),1.97-1.75(m ,2H). ¹³ C NMR(150MHz,CDCl ₃ )δ174.21,164.61,161.97,160.30,152.06,151.39,149.05,144.90,140.86,130.51,130.09,117.94,117.22,115.52,114.07,111.80,111.66,72.68,48.40 , 44.57, 41.85, 41.41, 40.08, 38.24, 32.32, 31.63. HRMS calculated for C ₂₆ H ₂₃ ClF ₂ N ₆ O ₂ S[M+H] ⁺ 557.13326. Found 557.13158.

Example 7

This example is used to illustrate the preparation method of the compound represented by formula (3-5).

At room temperature, the compound represented by formula (3-1) (1.00mmol, 1eq) was dissolved in 10mL of anhydrous methanol, and hydroxylamine hydrochloride (1.50mmol, 1.5eq) and triethylamine (2.00mmol, 2.0eq) were added, Continue to react at room temperature for 5h. The reaction was completed, the reaction system was poured into 20 mL of water, extracted with ethyl acetate, the organic phase was washed with 1N dilute hydrochloric acid and saturated sodium bicarbonate successively, dried over sodium sulfate, concentrated, and column chromatography obtained the formula (3-5). compound.

Formula (3-5): white solid, yield 91%, mp 158-159°C, ¹ H NMR (600MHz, CDCl ₃ ) δ 9.34(brs, 1H), 8.56-8.48(m, 1H), 8.38(d , J=7.2Hz, 1H), 8.28(s, 1H), 7.67(s, 1H), 7.32–7.27(m, 1H), 7.20–7.10(m, 1H), 6.90(t, J=7.8Hz, 2H), 6.07(t, J＝10.8Hz, 1H), 5.44(s, 2H), 4.59(d, J＝13.8Hz, 1H), 4.03(d, J＝11.4Hz, 1H), 3.80(dd, J=16.8, 9.0Hz, 1H), 3.63 (dd, J=16.8, 9.0Hz, 1H), 3.32 (t, J=11.4Hz, 2H), 2.88–2.81 (m, 1H), 2.24 (d, J =13.2Hz,1H),2.14(d,J=13.2Hz,1H),1.89-1.77(m,2H) ^.13C NMR(100MHz, _CDCl3 )δ174.37,164.80,162.58(d,J=8.1Hz) ,160.08(d,J＝8.1Hz),152.29,151.72,149.35,145.09,141.04,130.60(t,J＝10.1Hz),130.10,117.92,117.35,115.72(t,J＝16.2Hz),114.20,111.97 (t, J=6.1Hz), 111.78 (t, J=6.1Hz), 72.87 (t, J=3.0Hz), 48.39, 44.65, 41.99, 41.54, 40.22, 38.33, 32.45, 31.78. HRMS calculated value C ₂₆ H ₂₃ F ₂ N ₇ O ₃ S[M+Na] ⁺ 574.14434. Found 574.14738.

Example 8

This example is used to illustrate the preparation method of the compound represented by formula (3-6).

At 0°C, the compound represented by formula (3-5) (0.50mmol, 1eq) was dissolved in 5mL of anhydrous tetrahydrofuran, sodium hydride (0.75mmol, 1.5eq) was slowly added, the reaction was continued for 0.5 hours, and then iodine was added dropwise Methane (0.60 mmol, 1.2 eq), the reaction was complete. The temperature was raised to room temperature, 10 mL of water was added, the system was extracted with ethyl acetate, the organic phase was dried, concentrated, and the compound represented by formula (3-6) was obtained by column chromatography.

Formula (3-6): white solid, yield 74%, mp 144-145°C, ¹ H NMR (600 MHz, CDCl ₃ ) δ 8.56 (d, J=4.2 Hz, 1H), 8.53 (d, J=7.8 Hz,1H),8.35(s,1H),7.67(s,1H),7.32–7.28(m,1H),7.25–7.19(m,1H),6.92(t,J=8.4Hz,2H),6.08 (t, J=10.8Hz, 1H), 5.43 (s, 2H), 4.60 (d, J=13.2Hz, 1H), 4.17–4.01 (m, 4H), 3.81 (dd, J=16.8, 12.6Hz, 1H), 3.63(dd, J＝16.8, 9.0Hz, 1H), 3.34(t, J＝10.2Hz, 2H), 2.88(t, J＝12.6Hz, 1H), 2.25(d, J＝12.0Hz, 1H), 2.17(d, J=13.2Hz, 1H), 1.92-1.77(m, 2H). ¹³ C NMR (100MHz, CDCl ₃ )δ174.30, 164.72, 162.69(d, J=8.1Hz), 160.19(d , J＝8.1Hz), 152.34, 151.83, 149.65, 145.26, 143.90, 138.50, 132.65, 130.65(t, J＝10.1Hz), 118.24, 117.86, 115.83(t, J＝16.2Hz), 113.64, 112.05(d , J=6.1Hz), 111.85 (d, J=6.1Hz), 72.94 (t, J=3.0Hz), 62.60, 48.61, 44.75, 42.08, 41.63, 40.34, 32.57, 31.86. HRMS calculated value C ₂₇ H ₂₅ F ₂ N ₇ O ₃ S[M+Na] ⁺ 588.15999. Found 588.16178.

Example 9

This example is used to illustrate the preparation methods of compounds represented by formula (3-7), formula (3-8), formula (3-9) and formula (3-10).

Specifically, taking the preparation of the compound represented by formula (3-7) as an example

At room temperature, the compound represented by formula (3-1) (1.00 mmol, 1 eq), methylamine solution (1.50 mmol, 1.50 eq, 33 wt % ethanol solution) and sodium triacetoxyborohydride (1.50 mmol, 1.50 eq) were successively added to 10 mL of 1,2-dichloroethane, and the reaction was stirred for 5 h. After the reaction was completed, 20 mL of water was added, extracted with dichloromethane, the organic phase was washed with saturated sodium bicarbonate, dried over sodium sulfate, and concentrated. and further purified by silica gel column chromatography to obtain the compound represented by formula (3-7).

Formula (3-7): white solid, yield 75%, mp 133-135°C, ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.50 (d, J=4.8 Hz, 1H), 8.25 (d, J=8.0 Hz,1H),7.65(s,1H),7.36–7.27(m,1H),7.11(dd,J=8.0,4.8Hz,1H),6.91(t,J=8.4Hz,2H),6.07(dd , J=12.0, 9.6Hz, 1H), 5.41(s, 2H), 4.57(d, J=13.2Hz, 1H), 4.19(s, 2H), 4.06(d, J=13.2Hz, 1H), 3.90 (s, 1H), 3.80 (dd, J=17.2, 12.0Hz, 1H), 3.62 (dd, J=17.2, 9.2Hz, 1H), 3.40–3.25 (m, 2H), 2.84 (t, J=12.4 Hz, 1H), 2.53(s, 3H), 2.25(d, J=12.4Hz, 1H), 2.15(d, J=12.4Hz, 1H), 1.94–1.73(m, 2H). ¹³ C NMR (150MHz) , CDCl ₃ )δ174.37,165.07,162.10(d,J=5.1Hz),160.43(d,J=5.1Hz),152.20,151.54,149.06,145.04,141.61,130.57(t,J=7.1Hz),130.22, 117.93, 116.85, 115.66, 114.53, 111.91, 111.75, 72.80, 48.20, 47.24, 44.58, 41.89, 41.46, 40.21, 35.27, 32.42, 31.76. HRMS calculated C ₂₇ H ₂₇ F ₂ N ₇ O ₂ S[ ] ⁺ 552.19878. Measured 552.19872.

Formula (3-8): white solid, yield 68%, mp 131-132°C, ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.46 (d, J=4.8 Hz, 1H), 8.21 (d, J=8.4 Hz, 1H), 7.59(s, 1H), 7.29–7.22(m, 1H), 7.08(dd, J=8.0, 4.8Hz, 1H), 6.85(t, J=8.4Hz, 2H), 6.00(d , J＝9.6Hz, 1H), 5.34(s, 2H), 4.52(d, J＝13.2Hz, 1H), 4.00(d, J＝13.2Hz, 1H), 3.90(s, 2H), 3.74(dd , J＝17.2, 9.6Hz, 1H), 3.56(dd, J＝13.2, 8.4Hz, 1H), 3.27–3.23(m, 2H), 2.78(t, J＝11.2Hz, 1H), 2.33(s, 6H), 2.18 (d, J=14.4Hz, 1H), 2.09 (d, J=13.2Hz, 1H), 1.83–1.70 (m, 2H). ¹³ C NMR (150MHz, CDCl ₃ ) δ 174.25, 164.81, 161.95 (d, J=5.1Hz), 160.28 (d, J=5.1Hz), 152.09, 151.54, 148.85, 144.89, 141.36, 130.46 (t, J=7.1Hz), 130.39, 117.87, 116.74, 115.51 (t, J = 10.1Hz), 115.09, 111.78, 111.63, 72.65, 55.70, 48.13, 44.94, 44.42, 41.75, 41.34, 40.07, 32.29, 31.64. HRMS calculated value C ₂₈ H ₂₉ F ₂ N ₇ O ₂ S[M+H] ⁺ 566.21443. Measured value 566.21471.

Formula (3-9): white solid, yield 77%, mp123-125°C, ¹ H NMR (400MHz, CDCl ₃ )δ8.36(s, 1H), 7.95(s, 1H), 7.60(s, 1H ), 7.37–7.27 (m, 1H), 7.18–6.80 (m, 3H), 6.12–5.98 (m, 1H), 5.16 (s, 2H), 4.50 (d, J=13.2Hz, 1H), 4.23– 3.71(m, 4H), 3.61(dq, J=17.6, 9.2Hz, 1H), 3.34–3.08 (m, 2H), 3.00–2.53 (m, 2H), 2.47–2.04 (m, 5H), 1.91– 1.39 (m, 4H). ¹³ C NMR (100 MHz, CDCl ₃ ) δ 174.31, 174.06, 164.37, 162.54 (d, J=8.1 Hz), 160.04 (d, J=8.1 Hz), 152.24, 150.65, 149.61, 145.07, 130.57(t,J＝11.1Hz),129.80,127.31,117.95,117.90,117.37,115.69(t,J＝16.2Hz),111.93(d,J＝6.1Hz),111.74(d,J＝6.1Hz), 81.84, 74.72, 72.81, 48.77, 44.62, 41.96, 41.50, 40.20, 32.44, 31.75. HRMS calculated for C ₂₉ H ₂₉ F ₂ N ₇ O ₂ S[M+H] ⁺ 578.21443. Found 578.21619.

Formula (3-10): white solid, yield 69%, mp 117-118°C, ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.51 (d, J=4.8 Hz, 1H), 8.26 (d, J=8.4 Hz, 1H), 7.66(s, 1H), 7.35–7.27(m, 1H), 7.12(dd, J=8.4, 4.8Hz, 1H), 6.91(t, J=8.4Hz, 2H), 6.07(dd , J＝12.0, 9.2Hz, 1H), 5.39(s, 2H), 4.59(d, J＝13.6Hz, 1H), 4.11–4.00(m, 3H), 3.80(dd, J＝17.2, 12.0Hz, 1H), 3.63(dd, J=17.2, 9.2Hz, 1H), 3.37-3.24(m, 2H), 2.84(t, J=11.8Hz, 1H), 2.73-2.55(m, 4H), 2.23(d , J=12.8Hz, 1H), 2.15 (d, J=12.8Hz, 1H), 1.90–1.70 (m, 6H). ¹³ C NMR (150MHz, CDCl ₃ ) δ 174.21, 164.80, 161.89 (d, J=6.1 Hz), 160.23(d, J＝6.1Hz), 152.04, 151.40, 148.70, 144.83, 142.15, 130.41(t, J＝7.1Hz), 130.35, 117.81, 116.55, 115.47(t, J＝10.1Hz), 114.93 ,111.71,111.57,72.59,53.91,52.00,48.06,44.37,41.69,41.28,40.03,32.23,31.59,23.31.HRMS calculated value C ₃₀ H ₃₁ F ₂ N ₇ O ₂ S[M+H] ⁺ 592.23008. Measured The value is 592.23083.

Example 10

This example is used to illustrate the preparation method of the compound represented by formula (3-11).

At room temperature, the compound represented by formula (3-1) (1.00mmol, 1eq), ethylene glycol (1.50mmol, 1.5eq) and p-toluenesulfonic acid (0.1mmol, 0.1eq) were added to 10mL of chloroform in sequence After the reaction was completed, 20 mL of water was added, extracted with dichloromethane, the organic phase was washed with saturated brine, dried over sodium sulfate, concentrated, and further purified by silica gel column chromatography to obtain the formula (3- 11) The compound shown.

Formula (3-11): white solid, yield 71%, mp 127-128°C, ¹ H NMR (600 MHz, CDCl ₃ ) δ 8.66-8.57 (m, 1H), 8.54-8.43 (m, 1H), 7.65 (s, 1H), 7.32–7.27 (m, 1H), 7.13 (dd, J=8.4, 4.8Hz, 1H), 6.91 (t, J=7.8Hz, 2H), 6.07 (dd, J=14.4, 6.6 Hz, 1H), 5.64–5.24 (m, 3H), 4.59 (d, J=12.0Hz, 1H), 4.09–4.03 (m, 1H), 3.82–3.76 (m, 1H), 3.62 (dd, J= 16.8, 9.6Hz, 1H), 3.33 (dd, J=19.2, 8.4Hz, 2H), 2.88–2.80 (m, 1H), 2.30–2.26 (m, 1H), 2.14–2.09 (m, 1H), 1.87 -1.76(m, 2H), 1.27-1.17(m, 4H). ¹³ C NMR(100MHz, CDCl ₃ )δ174.20, 164.11, 162.63(d, J=8.1Hz), 160.13(d, J=8.1Hz), 152.26,150.06,149.13,145.21,142.66,131.73,130.66(d,J＝10.1Hz),120.13,118.00,115.73(d,J＝16.2Hz),113.85,112.01(d,J＝6.1Hz),111.82( d, J=6.1Hz), 100.22, 72.93 (t, J=3.0Hz), 65.51, 63.71, 49.16, 44.78, 42.14, 41.55, 40.22, 32.49, 31.77. HRMS calculated value C ₂₈ H ₂₆ F ₂ N ₆ O ₄ S[M+H] ⁺ 581.17771. Measured value 581.17399.

Example 11

This example is used to illustrate the preparation method of the compound represented by formula (3-13).

At 0°C, the compound represented by formula (3-2) (1.00mmol, 1eq) and diethylaminosulfur trifluoride (1.50mmol, 1.5eq) were sequentially added to 10mL of dichloromethane, and the temperature was raised to room temperature for reaction 6h, the reaction was completed, 20 mL of water was added, extracted with dichloromethane, the organic phase was washed with saturated brine, dried over sodium sulfate, concentrated, and further purified by silica gel column chromatography to obtain the compound represented by formula (3-13) .

Formula (3-13): white solid, yield 68%, mp 151-153°C, ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.50 (d, J=4.4 Hz, 1H), 8.14 (d, J=8.0 Hz,1H),7.60(s,1H),7.29–7.20(m,1H),7.14(dd,J=8.0,4.8Hz,1H),6.85(t,J=8.4Hz,2H),6.01(dd , J＝11.6, 9.6Hz, 1H), 5.66(d, J＝48.0Hz, 2H), 5.38(s, 2H), 4.53(d, J＝13.6Hz, 1H), 3.99(d, J＝12.4Hz ,1H),3.74(dd,J＝17.2,12.0Hz,1H),3.56(dd,J＝17.2,9.0Hz,1H),3.33–3.22(m,2H),2.80(t,J＝11.6Hz, 1H), 2.25–2.05 (m, 2H), 1.87–1.67 (m, 2H). ¹³ C NMR (150MHz, CDCl ₃ )δ174.22, 164.57, 161.92, 160.28, 152.06, 151.35, 149.08, 144.86, 139.83 (t, J=14.2Hz), 130.46(t, J=7.1Hz), 129.74, 117.90, 117.37, 115.48(t, J=11.1Hz), 114.37, 111.75, 111.60, 78.20, 72.63, 48.24, 44.41, 41.74, 41.29, 40.02, 32.24, 31.58. HRMS calculated for C ₂₆ H ₂₃ F ₃ N ₆ O ₂ S[M+H] ⁺ 541.16281. Found 541.16508.

Example 12

This example is used to illustrate the preparation method of the compound represented by formula (3-14).

At 0°C, the compound represented by formula (3-1) (1.00mmol, 1eq) and diethylaminosulfur trifluoride (1.50mmol, 1.5eq) were sequentially added to 10mL of dichloromethane, and the temperature was raised to room temperature for reaction 6h, the reaction was completed, 20 mL of water was added, extracted with dichloromethane, the organic phase was washed with saturated brine, dried over sodium sulfate, concentrated, and further purified by silica gel column chromatography to obtain the compound represented by formula (3-14) .

Formula (3-14): white solid, yield 70%, mp 157-158°C, ¹ H NMR (600 MHz, CDCl ₃ ) δ 8.58 (d, J=4.8 Hz, 1H), 8.26 (d, J=8.4 Hz,1H),7.65(s,1H),7.31–7.26(m,1H),7.23(dd,J=8.4,4.8Hz,1H),6.94(t,J=54.0Hz,1H),6.90(t , J＝8.4Hz, 2H), 6.07(dd, J＝12.0, 9.0Hz, 1H), 5.43(s, 2H), 4.57(d, J＝13.8Hz, 1H), 4.04(d, J＝13.8Hz) ,1H),3.79(dd,J＝17.4,12.0Hz,1H),3.62(dd,J＝17.4,9.0Hz,1H),3.37–3.28(m,2H),2.88(t,J＝12.6Hz, 1H), 2.25(d, J=13.8Hz, 1H), 2.16 (d, J=10.8Hz, 1H), 1.93–1.85 (m, 1H), 1.85–1.73 (m, 1H). ¹³ C NMR (150MHz) , CDCl ₃ )δ174.18,164.44,162.29,160.63,152.32,151.47,149.91,145.31,138.43(t,J=30.2Hz),130.62(t,J=7.1Hz),130.41,118.37,117.81,115.83(t,J=7.1Hz) J=10.1Hz), 112.50, 112.19, 112.01, 111.86, 72.94, 48.67, 44.75, 42.07, 41.62, 40.30, 32.54, 31.83. HRMS calculated value C ₂₆ H ₂₂ F ₄ N ₆ O ₂ S[M+H] ⁺ 559.17858. Measured value 559.17683.

Example 13

This example is used to illustrate the preparation method of the compound represented by the formula (3-16).

Under nitrogen protection, the compound represented by formula (3-1) (1.00 mmol, 1 eq) and (triphenylphosphonium) difluoroacetic acid inner salt (2.0 mmol, 2.0 eq) were successively added to 10 mL of anhydrous N , N-dimethylformamide, heated to 60 ℃, reacted for 1 h, then added tetrabutylammonium fluoride (3mL, 3.00mmol, 3eq, 1M tetrahydrofuran solution), continued to stir the reaction for 30min, the reaction was completed, add 60mL water, extracted with ethyl acetate, the organic phase was washed with saturated brine, dried over sodium sulfate, concentrated, and further purified by silica gel column chromatography to obtain the compound represented by formula (3-16).

Formula (3-16): white solid, yield 89%, mp 142-144°C, ¹ H NMR (600 MHz, CDCl ₃ ) δ 8.56 (d, J=4.2 Hz, 1H), 8.09 (d, J=8.4 Hz, 1H), 7.66 (s, 1H), 7.33–7.27 (m, 1H), 7.22–7.15 (m, 1H), 6.91 (t, J=8.4Hz, 2H), 6.07 (t, J=10.8Hz) ,1H),5.43(s,2H),4.58(d,J＝13.8Hz,1H),4.05(d,J＝13.8Hz,1H),3.95–3.70(m,3H),3.63(dd,J＝ 17.4, 9.0Hz, 1H), 3.33(t, J＝12.6Hz, 2H), 2.87(t, J＝12.6Hz, 1H), 2.24(d, J＝13.2Hz, 1H), 2.15(d, J＝ 13.2Hz, 1H), 1.90–1.75 (m, 2H). ¹³ C NMR (150MHz, CDCl ₃ ) δ 174.35, 164.92, 162.32 (d, J=6.1 Hz), 160.66 (d, J=6.1 Hz), 152.38, 151.66,149.36,145.31,134.90,130.66(t,J＝10.6Hz),130.07,125.37(q,J＝277.8Hz),117.84,117.53,115.88(t,J＝16.2Hz),115.22,112.06,111.89, 72.99, 48.58, 44.78, 42.11, 41.68, 40.38, 33.74 (d, J=31.7 Hz), 32.57, 31.90. HRMS calculated value C ₂₇ H ₂₃ F ₅ N ₆ O ₂ S[M+H] ⁺ 591.15961. Measured value 591.15960.

Example 14

This example is used to illustrate the preparation method of the compound represented by formula (3-21).

Under nitrogen protection, the compound represented by formula (3-1) (1.00 mmol, 1 eq) and (triphenylphosphonium) difluoroacetic acid inner salt (2.0 mmol, 2.0 eq) were successively added to 10 mL of anhydrous N , N-dimethylformamide, heated to 80 °C, reacted for 2 h, after the reaction was completed, 60 mL of water was added, extracted with ethyl acetate, the organic phase was washed with saturated brine, dried over sodium sulfate, concentrated, and further washed with silica gel After purification by column chromatography, the compound represented by the formula (3-21) was obtained.

Formula (3-21): white solid, yield 65%, mp168-169°C, ¹ H NMR (600MHz, DMSO-d ₆ )δ8.55(s, 1H), 8.32(d, J=8.4Hz, 1H ), 8.03 (d, J=3.6Hz, 1H), 7.52–7.45 (m, 1H), 7.27 (dd, J=8.4, 4.8Hz, 1H), 7.15 (t, J=8.4Hz, 2H), 6.23 (d,J＝28.8Hz,1H),6.02(dd,J＝12.6,9.0Hz,1H),5.57(d,J＝17.2Hz,1H),5.48(d,J＝17.2Hz,1H),4.34 (d, J=13.2Hz, 1H), 4.14 (d, J=13.2Hz, 1H), 3.91 (dd, J=17.2, 12.0Hz, 1H), 3.57–3.53 (m, 1H), 3.39 (t, J=11.6Hz, 1H), 3.32(t, J=12.6Hz, 1H), 2.81(t, J=12.6Hz, 1H), 2.11(dd, J=39.0, 13.2Hz, 2H), 1.84(q, J=12.6Hz, 1H), 1.56 (q, J=12.6, 1H). ¹³ C NMR (100MHz, DMSO-d ₆ ) δ 175.06, 164.82, 162.01 (d, J=8.1Hz), 159.53 (d, J= 8.1Hz), 152.22, 151.00, 149.19, 144.41, 133.77(d, J＝6.1Hz), 133.67(d, J＝6.1Hz), 131.46(t, J＝10.1Hz), 130.15(d, J＝6.1Hz) ), 120.02, 117.25, 115.70(t, J＝16.2Hz), 113.58(d, J＝3.0Hz), 112.37(d, J＝6.1Hz), 112.18(d, J＝6.1Hz), 75.11(d, J=14.2Hz), 74.78 (d, J=14.2Hz), 72.14 (t, J=3.0Hz), 48.46, 44.00, 41.28 (d, J=6.1Hz), 32.34, 31.88. HRMS calculated value C ₂₇ H ₂₂ F ₄ N ₆ O ₂ S[M+H] ⁺ 571.15338. Found 571.15289.

Example 15

This example is used to illustrate the preparation method of the compound represented by formula (3-22).

Under nitrogen protection, the compound represented by formula (3-1) (1.00mmol, 1eq) and ethyltriphenylphosphine bromide (1.2mmol, 1.2eq) were sequentially added to 10mL of anhydrous tetrahydrofuran, -15°C Then, slowly add lithium bistrimethylsilylamide (1.5mL, 1.5eq, 1M tetrahydrofuran solution) dropwise, warm to room temperature, continue the reaction for 2h, after the reaction is completed, add 10mL saturated ammonium chloride to quench and 10mL water, After extraction with ethyl acetate, the organic phase was washed with saturated brine, dried over sodium sulfate, concentrated, and further purified by silica gel column chromatography to obtain the compound represented by formula (3-22).

Formula (3-22): white solid, yield 65%, mp 119-120°C, ¹ H NMR (400MHz, CDCl ₃ ) δ 8.52 (t, J=4.8Hz, 1H), 8.26-8.04 (m, 1H) ), 7.67 (s, 1H), 7.34–7.28 (m, 1H), 7.14 (dd, J=8.0, 4.8Hz, 1H), 6.92 (t, J=8.4Hz, 2H), 6.74–6.56 (m, 1H), 6.15–5.96(m, 2H), 5.41(d, J＝19.2Hz, 2H), 4.61(d, J＝12.4Hz, 1H), 4.07(t, J＝12.0Hz, 1H), 3.81( dd,J＝16.8,12.0Hz,1H),3.64(dd,J＝17.2,9.2Hz,1H),3.32(t,J＝11.2Hz,2H),2.87(t,J＝11.6Hz,1H), 2.27-2.15(m, 2H), 2.15-2.10(m, 2H), 1.97(d, J=6.0Hz, 1H), 1.90-1.75(m, 2H). ¹³ C NMR (100MHz, CDCl ₃ )δ174. 45,165.05,165.03,162.68(d,J＝8.1Hz),160.18(d,J＝8.1Hz),152.34,148.43,145.22,142.20,131.52,130.63(t,J＝10.1Hz),123.12,118.25,117.84, 116.94,116.70,115.83(t,J=16.2Hz),112.03(t,J=6.1Hz),111.84(t,J=6.1Hz),72.93(t,J=3.0Hz),48.90,44.80,42.05, 41.63, 40.42, 32.57, 31.91, 19.07. HRMS calculated for C ₂₈ H ₂₆ F ₂ N ₆ O ₂ S[M+H] ⁺ 549.18788. Found 549.18675.

Example 16

This example is used to illustrate the preparation method of the compound represented by the formula (3-24).

At room temperature, the compound represented by formula (3-23) (1.00mmol, 1eq), tetrabutylammonium iodide (1.10mmol, 1.1eq) and silver nitrate (0.1mmol, 0.1eq) were sequentially added to 10mL of acetone , the reaction was stirred for 3 h, the reaction was completed, 10 mL of ethyl acetate was added, washed with 20 mL of water and saturated brine successively, dried over sodium sulfate, concentrated, and further purified by silica gel column chromatography to obtain the compound shown in formula (3-24). compound.

Formula (3-24): white solid, yield 90%, mp265-267°C, ¹ H NMR (600MHz, CDCl ₃ )δ8.57(s, 1H), 8.16(d, J=7.8Hz, 1H), 7.68(s,1H),7.33-7.28(m,1H),7.24-7.17(m,1H),6.93(t,J=7.8Hz,2H),6.13-6.05(m,1H),5.43(s, 2H), 4.59 (d, J=14.4Hz, 1H), 4.04 (d, J=13.2Hz, 1H), 3.87–3.77 (dd, J=17.2, 13.2Hz, 1H), 3.64 (dd, J=17.2 ,9.0Hz,1H),3.34(t,J＝12.0Hz,2H),2.87(t,J＝12.0Hz,1H),2.27(d,J＝15.6Hz,1H),2.17(d,J＝14.4 Hz, 1H), 1.90–1.78 (m, 2H). ¹³ C NMR (100MHz, DMSO-d ₆ ) δ 175.43, 164.49, 161.95 (d, J=8.1 Hz), 159.47 (d, J=8.1 Hz), 152.26 ,150.06,149.63,144.10,131.48(t,J＝10.1Hz),129.47,126.91,120.34,118.29,116.63,115.55(t,J＝16.2Hz),112.34(d,J＝5.1Hz),112.16(d , J＝6.1Hz), 84.12, 72.27, 48.72, 43.99, 41.29, 41.01, 32.30, 31.81, 23.73. HRMS calculated value C ₂₇ H ₂₁ F ₂ IN ₆ O ₂ S[M+H] ⁺ 659.05322. Measured value 659.04904 .

Example 17

This example is used to illustrate the preparation method of the compound represented by the formula (3-26).

At room temperature, the compound (1.00 mmol, 1 eq) represented by the formula (3-25) was dissolved in 10 mL of anhydrous methanol, Pd/C (50.00 mg, 10 wt %) was added, and the reaction system was replaced with hydrogen 3 times, and continued The reaction was carried out for 12h. After the reaction was completed, it was replaced with nitrogen three times, the system was filtered and concentrated to obtain the compound represented by formula (3-26).

Formula (3-26): yellow solid, yield 97%, mp142-143°C, ¹ H NMR (600MHz, DMSO-d ₆ )δ8.34(s, 1H), 8.12(d, J=7.8Hz, 1H ), 8.03(s, 1H), 7.55–7.43(m, 1H), 7.16(t, J=9.0Hz, 2H), 6.98(s, 1H), 6.01(t, J=10.8Hz, 1H), 5.70 (s, 2H), 5.20–5.00 (m, 2H), 4.33 (d, J=13.2Hz, 1H), 4.10 (d, J=13.2Hz, 1H), 3.90 (t, J=15.0Hz, 1H) ,3.54(dd,J＝17.2,8.6Hz,1H),3.35–3.20(m,2H),2.78(t,J＝13.2Hz,1H),2.08(t,J＝13.8Hz,2H),1.76– 1.65(m, 1H), 1.57–1.48(m, 1H). ¹³ C NMR (100MHz, DMSO-d ₆ ) δ 175.17, 165.68, 162.03 (d, J=7.1Hz), 159.54 (d, J=7.1Hz) ,152.25,151.49,148.52,147.67,144.39,131.53(t,J＝10.1Hz),130.03,120.09,115.73(t,J＝16.2Hz),114.08,112.42(d,J＝5.1Hz),112.23(d , J=5.1Hz), 107.27, 72.14, 47.42, 44.05, 41.28, 32.44, 31.95. HRMS calculated value C ₂₅ H ₂₃ F ₂ N ₇ O ₂ S[M+H] ⁺ 524.16748. Measured value 524.16795.

Test Example 1: In vivo activity against cucumber downy mildew

The test and investigation methods refer to SOP-SC-1098 Potted Cucumber Downy Mildew Method in the Fungicide Volume of "Standard Practice for Pesticide Biological Activity Test" compiled by Kang Zhuo and Gu Baogen.

Table 1

*90%≦A≦100%; 75%≦B＜90%; “-” means not tested

It can be seen from Table 1 that most of the compounds of the present invention have good control effect on cucumber downy mildew. Formula (3-3), Formula (3-4), Formula (3-6)～(3-13), Formula (3-15), Formula (3-18)～(3-20), Formula (3) -23), formula (3-25), formula (3-28) and formula (3-29) when the administration concentration is 20mg/L, the control effect on cucumber downy mildew is all in grade A, reach more than 90%.

Test Example 2: In vitro activity of inhibiting the growth of oomycete pathogens: Phytophthora capsicum, Phytophthora infestans, Phytophthora litchi, Phytophthora sojae, etc.

Test Method for Determination of Biological Activity in Pharmaceutical Chambers by Microplate Method

Phytophthora lychee, Phytophthora sojae: inoculate the target bacteria in PDB or V8 juice liquid medium for 96 hours, collect fresh mycelia after filtration, then weigh 0.1g of mycelium and put it into 50mL of PDB liquid After the culture medium, the mycelium was smashed into small hyphal segments with a tissue masher to prepare a suspension of hyphal segments, which was placed at 4°C for later use.

Phytophthora infestans: Inoculate Phytophthora infestans on the V8 medium plate and cultivate for 12 days. After it produces a large number of sporangia, add sterile water and transfer the plate to a 4°C refrigerator for 1 hour, and then transfer to a At room temperature, zoospore release is induced. After the zoospores were fully released, a spore suspension with a spore concentration of 10 ⁵ spores/mL was prepared and placed at 4°C for later use.

The test agent was prepared into a 2000 mg/L mother solution with dimethyl sulfoxide, then diluted with sterile water to a concentration of 0.1 mg/L, and placed at 4°C for later use.

The spore suspension (hyphal segment suspension) and a series of gradient liquids prepared in advance were added to each microwell in order of 100 μl+100 μl, and then the 96-well microplate was placed at 25 ° C (Phytophthora infestans). 18°C) in an incubator for static culture, and after 3-4 days (7 days for Phytophthora infestans), the OD ₅₉₅ (absorbance value at 595 nm) value of each treatment was detected with a microplate reader. Calculate the indoor virulence of the agent to the target bacteria. The test results are shown in Table 2.

Table 2

*95%≦A≦100%; 90%≦B<95%; 85%≦C<90%; 75%≦D<85%; E<75%; “-” means not tested

It can be seen from Table 2 that under the administration concentration of 0.1 mg/L, the compounds of the present invention have significant inhibitory effects on the mycelial growth of the four Phytophthora species, which are shown as Grade A, with an inhibition rate greater than 95%, especially for The activity of Phytophthora lychee obviously has great potential for development.

6 compounds represented by formula (3-3), formula (3-12), formula (3-14), formula (3-15), formula (3-20) and formula (3-29) are effective against soybean disease The mycelial growth inhibition of mold is C grade and above, and the inhibition rate is greater than 85%; formula (3-12), formula (3-15), formula (3-20), formula (3-25), formula ( 3-28) and other five compounds shown in the mycelium growth inhibition of Phytophthora capsicum grade A, the inhibition rate is greater than 95%; formula (3-1), formula (3-3), formula (3-4) , formula (3-12), formula (3-13), formula (3-15), formula (3-16), formula (3-19), formula (3-20), formula (3-25), The 12 compounds represented by the formula (3-28) and the formula (3-29) etc. have the inhibitory effect on the mycelial growth of Phytophthora infestans grade C and above, and the inhibition rate is greater than 85%; formula (3-1) , formula (3-3), formula (3-4), formula (3-12), formula (3-13), formula (3-14), formula (3-16), formula (3-19), The 10 compounds represented by the formula (3-20) and the formula (3-28) etc. have the inhibitory effect on the mycelial growth of Phytophthora litchi as C grade and above, and the inhibition rate is greater than 85%.

In conclusion, the above compounds have great potential for development.

The preferred embodiments of the present invention have been described above in detail, however, the present invention is not limited thereto. Within the scope of the technical concept of the present invention, a variety of simple modifications can be made to the technical solutions of the present invention, including the combination of various technical features in any other suitable manner. These simple modifications and combinations should also be regarded as the content disclosed in the present invention. All belong to the protection scope of the present invention.

Claims (10)

1. a compound of a structure represented by formula (1) containing a fused heterocyclic structure or agrochemically acceptable salts, hydrates and solvates thereof,

In formula (1), R is selected from hydrogen, methyl, n-propyl, C ₄ -C ₆ alkyl, C ₂ -C ₆ alkenyl, C ₂ -C ₆ alkynyl, C ₁ -C ₆ haloalkyl, C ₂ -C ₆ halo Alkenyl, C ₂ -C ₆ haloalkynyl, C ₁ -C ₄ hydroxyalkyl, C ₂ -C ₄ alkoxyalkyl, C ₂ -C ₆ alkylaminoalkyl, C ₃ -C _{6 Dialkylaminoalkyl} , C3 _{- C8cycloalkylaminoalkyl} , C2 _- C4alkylcarbonyl, aldehyde, aldoxime, nitro, amino, cyano, fluorine, bromine, C2 _- C ₆ aldoxime ether group, C ₂ -C ₆ oxygen-containing cycloalkyl group, C ₃ -C ₆ cycloalkyl group, C ₄ -C ₁₀ cycloalkyl alkyl group, C ₄ -C ₁₀ alkyl cycloalkyl group, C ₅ -C ₁₀ alkylcycloalkylalkyl, C ₃ -C ₆ halocycloalkyl, hydroxyl, C ₁ -C ₄ alkoxy, C ₁ -C ₄ haloalkoxy, C ₁ -C ₄ alkylthio , C ₁ -C ₄ alkylsulfinyl, C ₁ -C ₄ alkylsulfonyl, C ₁ -C ₄ haloalkylthio, C ₁ -C ₄ haloalkylsulfinyl, C ₁ -C ₄ haloalkylsulfonyl Acyl, C ₁ -C ₄ alkylamino, C ₂ -C ₈ dialkylamino, C ₃ -C ₆ cycloalkylamino, C ₂ -C ₄ alkylcarbonylamino, hydroxylamine, C ₁ -C ₄ alkane Oxyamino, C ₂ -C ₄ haloalkylcarbonylamino, C ₂ -C ₄ alkylcarbonyl, C ₂ -C ₆ alkoxycarbonyl, C ₂ -C ₆ alkylcarbonyloxy, C ₂ -C ₆ alkylcarbonyl Sulfanyl, C ₂ -C ₆ alkylaminocarbonyl, C ₃ -C ₈ dialkylaminocarbonyl or C ₃ -C ₆ trialkylsilyl; R ₁ , R ₂ and R ₃ are each independently selected from H, C ₁ -C ₆ alkyl, C ₂ -C ₆ alkenyl, C ₂ -C ₆ alkynyl, C ₁ -C ₆ haloalkyl, C ₂ - C ₆ haloalkenyl, C ₂ -C ₆ haloalkynyl, C ₁ -C ₄ hydroxyalkyl, C ₂ -C ₄ alkoxyalkyl, C ₂ -C ₆ alkylaminoalkyl, C ₃ -C ₆ dialkylaminoalkyl, C ₃ -C ₈ cycloalkylaminoalkyl, C ₂ -C ₄ alkylcarbonyl, aldehyde, aldoxime, nitro, amino, cyano, halogen, C ₂ - C ₆ aldoxime ether group, C ₂ -C ₆ oxygen-containing cycloalkyl, C ₃ -C ₆ cycloalkyl, C ₄ -C ₁₀ cycloalkyl alkyl, C ₄ -C ₁₀ alkylcycloalkyl, C ₅ -C ₁₀ alkylcycloalkylalkyl, C ₃ -C ₆ halocycloalkyl, hydroxyl, C ₁ -C ₄ alkoxy, C ₁ -C ₄ haloalkoxy, C ₁ -C ₄ alkylthio base, C ₁ -C ₄ alkylsulfinyl, C ₁ -C ₄ alkylsulfonyl, C ₁ -C ₄ haloalkylthio, C ₁ -C ₄ haloalkylsulfinyl, C ₁ -C ₄ haloalkyl Sulfonyl, C ₁ -C ₄ alkylamino, C ₂ -C ₈ dialkylamino, C ₃ -C ₆ cycloalkylamino, C ₂ -C ₄ alkylcarbonylamino, hydroxylamine, C ₁ -C ₄ Alkoxyamino, C ₂ -C ₄ haloalkylcarbonylamino, C ₂ -C ₄ alkylcarbonyl, C ₂ -C ₆ alkoxycarbonyl, C ₂ -C ₆ alkylcarbonyloxy, C ₂ -C ₆ alkyl Carbonylthio, C ₂ -C ₆ alkylaminocarbonyl, C ₃ -C ₈ dialkylaminocarbonyl and C ₃ -C ₆ trialkylsilyl; R ₄ is 2,6-difluorophenyl or 2-chloro-6-[(methylsulfonyl)oxy]phenyl. 2. The compound of claim 1, wherein, in formula (1), R is selected from H, methyl, n-propyl, C ₂ -C ₆ alkenyl, C ₂ -C ₆ alkynyl, C ₁ -C ₆ haloalkyl, C ₂ -C ₆ haloalkenyl, C ₂ -C ₆ haloalkynyl, C ₁ -C ₄ hydroxyalkyl, C ₁ -C ₄ acylalkyl, C ₂ -C ₄ alkoxyalkyl, C ₂ -C ₆ alkylaminoalkyl, C ₃ -C ₆ dialkylaminoalkyl, C ₃ -C ₈ cycloalkylamino alkyl, C ₂ -C ₆ alkylamino, C ₃ -C ₆ dialkylamino, hydroxylamine, C ₁ -C ₄ alkoxyamine , C ₁ -C ₄ alkoxy, C ₂ -C ₄ alkylcarbonyl, C ₁ -C ₄ alkylsulfonyl, aldehyde group, C ₁ -C ₄ aldoxime group, hydroxyl, nitro, amino, cyano group , halogen, C ₂ -C ₆ aldoxime ether group, 1,3-dioxocyclopentyl; R ₁ , R ₂ and R ₃ are each independently selected from H, methyl, ethyl, n-propyl, isopropyl, cyclopropyl, C ₂ -C ₆ alkenyl, C ₂ -C ₆ alkynyl, C ₁ -C ₆ haloalkyl, C ₂ -C ₆ haloalkenyl, C ₂ -C ₆ haloalkynyl, C ₁ -C ₄ hydroxyalkyl, C ₁ -C ₄ acylalkyl, C ₂ -C ₄ Alkoxyalkyl, C ₂ -C ₆ alkylaminoalkyl, C ₃ -C ₆ dialkylaminoalkyl, C ₃ -C ₈ cycloalkylaminoalkyl, C ₂ -C ₆ alkylamino, C ₃ -C ₆ dialkylamino, hydroxylamine, C ₁ -C ₄ alkoxyamine, C ₁ -C ₄ alkoxy, C ₂ -C ₄ alkylcarbonyl, C ₁ -C ₄ alkylsulfonyl, Aldehyde group, aldoxime group, hydroxyl group, nitro group, amino group, cyano group, fluorine, chlorine, bromine, iodine, C ₂ -C ₆ aldoxime ether group and 1,3-dioxocyclopentyl; R ₄ is 2,6-difluorophenyl or 2-chloro-6-[(methylsulfonyl)oxy]phenyl. 3. The compound of claim 1, wherein, in formula (1), R is selected from H, methyl, n-propyl, n-butyl, tert-butyl, vinyl, propenyl, ethynyl, propynyl, chloromethyl, dichloromethyl, trichloromethyl, bromomethyl , dibromomethyl, tribromomethyl, fluoromethyl, difluoromethyl, trifluoromethyl, 1-chloroethyl, 2-chloroethyl, 1-fluoroethyl, 2-fluoroethyl, 1 ,1-difluoroethyl, 2,2-difluoroethyl, 1,2-difluoroethyl, 2,2,2-trifluoroethyl, 1,1,2,2,2-pentafluoroethyl , acetylmethyl, 1-chloro-vinyl, 2-chloro-vinyl, 2,2-dichlorovinyl, 1,2-dichlorovinyl, 1-fluoro-vinyl, 2-fluoro- Vinyl, 2,2-difluorovinyl, 1,2-difluorovinyl, fluoroethynyl, chloroethynyl, iodoethynyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl group, hydroxy-n-propyl, methoxymethyl, 1-methoxyethyl, 2-methoxyethyl, 3-methoxy-n-propyl, ethoxymethyl, 1-ethoxyethyl base, 2-ethoxyethyl, 3-ethoxyn-propyl, methylaminomethyl, 1-methylaminoethyl, 2-methylaminoethyl, methylamino-n-propyl, dimethylamino aminomethyl, 1-dimethylaminoethyl, 2-dimethylaminoethyl, dimethylamino-n-propyl,

Methylamino, dimethylamino, methylethylamino, hydroxylamine, methoxyamine, methoxy, ethoxy, acetyl, propionyl, methylsulfonyl, aldehyde, -CH=NOH, -CH =NOCH ₃ , hydroxy, nitro, amino, cyano, fluorine, bromine or 1,3-dioxolane; R ₁ , R ₂ and R ₃ are each independently selected from H, methyl, ethyl, n-propyl, isopropyl, cyclopropyl, n-butyl, tert-butyl, vinyl, propenyl, ethynyl, Propynyl, chloromethyl, dichloromethyl, trichloromethyl, bromomethyl, dibromomethyl, tribromomethyl, fluoromethyl, difluoromethyl, trifluoromethyl, 1-chloroethyl base, 2-chloroethyl, 1-fluoroethyl, 2-fluoroethyl, 1,1-difluoroethyl, 2,2-difluoroethyl, 1,2-difluoroethyl, 2,2 ,2-trifluoroethyl, 1,1,2,2,2-pentafluoroethyl, acetylmethyl, 1-chloro-vinyl, 2-chloro-vinyl, 2,2-dichlorovinyl , 1,2-dichlorovinyl, 1-fluoro-vinyl, 2-fluoro-vinyl, 2,2-difluorovinyl, 1,2-difluorovinyl, fluoroethynyl, chloroacetylene group, iodoethynyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, hydroxy-n-propyl, methoxymethyl, 1-methoxyethyl, 2-methoxyethyl, 3-methoxy-n-propyl, ethoxymethyl, 1-ethoxyethyl, 2-ethoxyethyl, 3-ethoxy-n-propyl, methylaminomethyl, 1-methyl Aminoethyl, 2-methylaminoethyl, methylamino-n-propyl, dimethylaminomethyl, 1-dimethylaminoethyl, 2-dimethylaminoethyl, dimethylamino-n-propyl base,

Methylamino, dimethylamino, methylethylamino, hydroxylamine, methoxyamine, methoxy, ethoxy, acetyl, propionyl, methylsulfonyl, aldehyde, -CH=NOH, -CH = _NOCH3 , hydroxy, nitro, amino, cyano, fluorine, chlorine, bromine, iodine and 1,3-dioxolane; R ₄ is 2,6-difluorophenyl or 2-chloro-6-[(methylsulfonyl)oxy]phenyl. 4. The compound of claim 3, wherein, in formula (1), _R is selected from -CHO, _-CH2OH , -CH(OH) _CH3 , _-CH2CH2OH , _-CH2OCH3 , -CH _{( CH3 ) OCH3} , _-CH2CH2OCH3 , _- CH=NOH, -CH=NOCH ₃ , -CH ₂ NHCH ₃ , -CH ₂ N(CH ₃ ) ₂ ,

_-CH3 , _-CH2Cl , _-CHClCH3 , _-CH2CH2Cl , _-CH2F , _-CHF2 , _-CF3 , _-CHFCH3 , _{-CH2CH2F , -CHFCH2F} , _- CF ₂ CH ₃ , -CH ₂ CHF ₂ , -CH ₂ CF ₃ , -CF ₂ CF ₃ , -CH ₂ CH ₂ CH ₃ , -C(CH ₃ ) ₃ , -COCH ₃ , -CH ₂ COCH ₃ , - COCH ₂ CH ₃ , -CH=CH ₂ , -CH=CF ₂ , -CH=CHCH ₃ , -C≡CH, -C≡CI, -C≡CCH ₃ , -OCH ₃ , -OH, -NO ₂ , _-NH2 , -NHCH3, -N( _CH3 ) ₂ , -N( _{CH2CH3 ) CH3} , -NHOH, _-NHOCH3 , -C≡N, _-Br or -H; R ₁ , R ₂ and R ₃ are all H; R ₄ is 2,6-difluorophenyl or 2-chloro-6-[(methylsulfonyl)oxy]phenyl. 5. The application of the compound containing a fused heterocyclic structure according to any one of claims 1 to 4 or agrochemically acceptable salts, hydrates and solvates thereof in the control of plant oomycete diseases. 6. The application according to claim 5, wherein the plant oomycete disease is selected from at least one pathogen in Phytophthora infestans, Phytophthora sojae, Phytophthora capsicum, Phytophthora litchi and Cucumber downy mildew. disease. 7. Use of the fused heterocyclic structure-containing compound or agrochemically acceptable salts, hydrates and solvates thereof as claimed in any one of claims 1 to 4 as pesticides and fungicides. 8. a bactericide, this bactericide is made up of active ingredient and auxiliary material, and described active ingredient comprises the compound of fused heterocyclic structure containing the structure shown in formula (1) described in any one of claim 1-4 or At least one of its agrochemically acceptable salts, hydrates and solvates. 9. The bactericide according to claim 8, wherein the content of the active ingredient is 1-99.9% by weight. 10. The bactericide according to claim 9, wherein the dosage form of the bactericide is selected from at least one of emulsifiable concentrate, suspending agent, wettable powder, powder, granule, water, poison bait, mother liquor and mother powder.