CN111848612B - Compound containing fused heterocyclic structure, preparation method and application thereof, and bactericide - Google Patents

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

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CN111848612B
CN111848612B CN202010760478.XA CN202010760478A CN111848612B CN 111848612 B CN111848612 B CN 111848612B CN 202010760478 A CN202010760478 A CN 202010760478A CN 111848612 B CN111848612 B CN 111848612B
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CN111848612A (en
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杨光富
李建龙
周立明
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Central China Normal University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system

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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 pesticide bactericides, in particular to a compound containing a fused heterocyclic structure and a preparation method thereof, application of the compound containing the fused heterocyclic structure in preventing and treating plant oomycete diseases, application of the compound containing the fused heterocyclic structure as a pesticide bactericide and a bactericide.
Background
The oomycetes are one of the important pathogenic bacteria causing plant diseases, have the characteristics of wide parasitic range, strong destructiveness, large harmfulness, rapid development and the like, and can harm most of main economic crops such as potatoes, tomatoes, hot peppers, grapes, tobaccos, hot peppers and the like. Meanwhile, diseases caused by the pesticide are difficult to control, so that great loss is brought to agricultural production.
The main phytopathogens of the oomycetes include phytophthora infestans, phytophthora sojae, phytophthora capsici, pythium ultimum, phytophthora litchi, peronospora cubensis and the like. Of these, phytophthora infestans is a typical pathogen that triggers late blight outbreaks in potatoes that have led to the occurrence of the historically well-known irish hunger 39313. Other phytopathogens can cause serious diseases, such as phytophthora capsici easily causes diseases of crops such as hot pepper, tomato, eggplant and melon, and downy mildew of melons and fruits caused by cucumber downy mildew.
The control of oomycete diseases is increasingly difficult, at present, chemical control is still the most simple and effective method in control measures, and a protective bactericide with multiple action sites and a systemic bactericide with single action site are mainly used in production. However, with the prolonged and long-term abuse of these fungicides, severe resistance to many pathogenic bacteria has developed.
Therefore, the development of novel oomycete bactericides without cross-resistance is becoming a development direction which is urgently needed in the field.
Disclosure of Invention
The invention aims to provide a novel compound containing a fused heterocyclic structure to achieve a good effect of preventing and treating oomycete diseases at a low concentration.
In order to achieve the above object, in a first aspect, the present invention provides a fused heterocyclic structure-containing compound having a structure represented by formula (1) or an agrochemically acceptable salt, hydrate and solvate thereof,
Figure BDA0002612930930000011
in the formula (1), the reaction mixture is,
r is selected from hydrogen, methyl, n-propyl and C4-C6Alkyl radical, C2-C6Alkenyl radical, C2-C6Alkynyl, C1-C6Haloalkyl, C2-C6Haloalkenyl, C2-C6Halogenated alkynyl, C1-C4Hydroxyalkyl radical, C2-C4Alkoxyalkyl group, C2-C6Alkylaminoalkyl, C3-C6Dialkylaminoalkyl radical、C3-C8Cycloalkylaminoalkyl radical, C2-C4Alkylcarbonyl, aldehyde, aldoximino, nitro, amino, cyano, fluoro, bromo, C2-C6Aldoxime ether group, C2-C6Oxygen-containing cycloalkyl radical, C3-C6Cycloalkyl radical, C4-C10Cycloalkylalkyl radical, C4-C10Alkyl cycloalkyl radical, C5-C10Alkyl cycloalkyl alkyl, C3-C6Halocycloalkyl, hydroxy, C1-C4Alkoxy radical, C1-C4Haloalkoxy, C1-C4Alkylthio radical, C1-C4Alkylsulfinyl radical, C1-C4Alkylsulfonyl radical, C1-C4Haloalkylthio, C1-C4Haloalkylsulfinyl radical, C1-C4Haloalkylsulfonyl group, C1-C4Alkylamino radical, C2-C8Dialkylamino radical, C3-C6Cycloalkylamino, C2-C4Alkylcarbonylamino, hydroxylamino, C1-C4Alkoxyamino group, C2-C4Haloalkylcarbonylamino, C2-C4Alkylcarbonyl group, C2-C6Alkoxycarbonyl, C2-C6Alkyl carbonyl oxy, C2-C6Alkylcarbonylthio group, C2-C6Alkylaminocarbonyl radical, C3-C8Dialkylaminocarbonyl or C3-C6A trialkylsilyl group;
R1、R2and R3Each independently selected from H, C1-C6Alkyl radical, C2-C6Alkenyl radical, C2-C6Alkynyl, C1-C6Haloalkyl, C2-C6Haloalkenyl, C2-C6Halogenated alkynyl, C1-C4Hydroxyalkyl radical, C2-C4Alkoxyalkyl group, C2-C6Alkylaminoalkyl, C3-C6Dialkylaminoalkyl, C3-C8Cycloalkylaminoalkyl radical, C2-C4Alkylcarbonyl, aldehyde group, aldoximino, nitro, amino, cyano, halogen, C2-C6Aldoxime ether group, C2-C6Oxygen-containing cycloalkyl radical, C3-C6Cycloalkyl radical, C4-C10Cycloalkylalkyl radical, C4-C10Alkyl cycloalkyl radical, C5-C10Alkyl cycloalkyl alkyl, C3-C6Halocycloalkyl, hydroxy, C1-C4Alkoxy radical, C1-C4Haloalkoxy, C1-C4Alkylthio radical, C1-C4Alkylsulfinyl radical, C1-C4Alkylsulfonyl radical, C1-C4Haloalkylthio, C1-C4Haloalkylsulfinyl radical, C1-C4Haloalkylsulfonyl group, C1-C4Alkylamino radical, C2-C8Dialkylamino radical, C3-C6Cycloalkylamino, C2-C4Alkylcarbonylamino, hydroxylamino, C1-C4Alkoxyamino group, C2-C4Haloalkylcarbonylamino, C2-C4Alkylcarbonyl group, C2-C6Alkoxycarbonyl, C2-C6Alkyl carbonyl oxy, C2-C6Alkylcarbonylthio group, C2-C6Alkylaminocarbonyl radical, C3-C8Dialkylaminocarbonyl and C3-C6A trialkylsilyl group;
R4is 2, 6-difluorophenyl or 2-chloro-6- [ (methylsulfonyl) oxy]A phenyl group.
Some exemplary explanations are provided below for the partial groups of the present invention, and the unrecited portions are explained with reference to the following exemplary explanations without particular description.
“C4-C6Alkyl "means an alkyl group having a total number of carbon atoms of 4 to 6, including straight chain alkyl groups, branched chain alkyl groups, such as straight chain alkyl groups which may have a total number of carbon atoms of 4, 5 or 6, branched chain alkyl groups, such as n-butyl, isobutyl, t-butyl, n-pentyl, isopentyl, n-hexyl, and the like. "C1-C6Definition of haloalkyl "with" C4-C6Alkyl "is similarly defined, except that" C "is1-C6Haloalkyl "wherein at least one H is substituted by a halogen atom and the total number of carbon atoms is different, e.g. 1,2, 3,4, 5 or 6H are substituted by at least one halogen atom selected from fluorine, chlorine, bromine, iodine and C1-C6The total number of carbon atoms of the haloalkyl groups is 1 to 6. "C1-C4Definition of hydroxyalkyl "with" C4-C6Alkyl "is similarly defined, except that" C "is1-C4At least one H on hydroxyalkyl is substituted by hydroxy, e.g. 1,2 or 3H may be substituted by hydroxy, and C1-C4The total number of carbon atoms in the hydroxyalkyl group is 1 to 4. "C2-C4Definitions of alkoxyalkyl groups with "C4-C6Alkyl "is similarly defined, except that" C "is2-C4At least one H on alkoxyalkyl "is substituted by alkoxy, e.g. 1,2 or 3H may be substituted by alkoxy, and C2-C4The total number of carbon atoms of the alkoxyalkyl group being 2 to 4, C2-C4Alkoxyalkyl may, for example, be represented by R1O-R2-, in which R1O is the same as C2-C4Alkoxy in alkoxyalkyl, R2Is the C2-C4Alkyl in alkoxyalkyl.
“C2-C6The alkenyl group "represents an alkenyl group having 2 to 6 carbon atoms in total, and may be, for example, an ethenyl group, a propenyl group, a butenyl group, or the like. "C2-C6Definition of haloalkenyl "with" C2-C6Alkenyl "is similarly defined, except that" C "is2-C6Haloalkenyl "wherein at least one H is substituted by a halogen atom, for example 1,2, 3,4, 5 or 6H may be substituted by at least one halogen atom selected from fluorine, chlorine, bromine, iodine.
“C2-C6Alkynyl "means alkynyl having 2 to 6 carbon atoms in total, and may be, for example, ethynyl, propynyl or butynyl. "C2-C6Definition of haloalkynyl "and“C2-C6alkynyl "is similarly defined, except that" C "is2-C6Haloalkynyl "is substituted with at least one H by a halogen atom, for example, 1,2, 3,4, 5 or 6H may be substituted with at least one halogen atom selected from fluorine, chlorine, bromine and iodine.
“C2-C6Alkylaminoalkyl "denotes a group having a total number of carbon atoms of 2 to 6, C2-C6Alkylaminoalkyl can be represented, for example, by R3-NH-R4-, and R3And R4The total number of carbon atoms of (a) is 2 to 6. "C3-C6Definition of dialkylaminoalkyl "with" C2-C6Alkylaminoalkyl "is as defined, this C3-C6Dialkylaminoalkyl radicals may be represented, for example, by R5-N(R6)-R7-, and R5、R6、R7The total number of carbon atoms of (a) is 3 to 6.
“C3-C8Cycloalkylamino alkyl "denotes a group having 3 to 8 carbon atoms in total, C3-C8Cycloalkylaminoalkyl can be represented, for example, by R8-R9-, in which R8Is a cyclic group containing a N atom, and the R8N atom of (1) and R9And (4) direct connection.
“C2-C4Alkylcarbonyl "represents a group having a total number of carbon atoms of 2 to 4, C2-C4Alkylcarbonyl may be represented, for example, by R10-CO-，R10Is namely C2-C4Alkyl in alkylcarbonyl.
"aldoximino" is represented by HON ═ CH-.
“C2-C6An aldoxime ether group "means a group having a total of 2 to 6 carbon atoms, C2-C6The aldoxime ether group can be represented, for example, by R11-ON ═ CH-, the R11Represents an alkyl group.
“C2-C6The "oxygen-containing cycloalkyl group" 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. "C3-C6Cycloalkyl radicals "Definition of (1) and "C2-C6Oxocycloalkyl "is similarly defined, except that" C "is3-C6The ring-constituting atoms of the cycloalkyl group "are all C atoms, and the total number of carbon atoms of the group is 3 to 6. "C4-C10Definition of cycloalkylalkyl "with" C2-C6Oxocycloalkyl "is defined analogously, except that" C "is4-C10The ring-constituting atoms of the cycloalkylalkyl group "are all C atoms, the total number of carbon atoms of the group being 4 to 10, the" C "group4-C10Cycloalkylalkyl "may be represented, for example, by R12-R13-, in which R12Is cycloalkyl, R13Is a mother nucleus structural group connecting cycloalkyl and the compound with the structure shown in the formula (1). "C4-C10Definition of alkylcycloalkyl "with" C4-C10Cycloalkylalkyl "is as defined, this C4-C10Alkylcycloalkyl can be represented, for example, by R14-R15-, in which R15Is cycloalkyl, and R14To substitute for the R15The alkyl group of H in (1).
“C5-C10Alkylcycloalkylalkyl "denotes a group having a total number of carbon atoms of from 5 to 10, which group may be represented, for example, by R16-R17-R18-, in which R17Is cycloalkyl, to which R is attached as alkyl16And R18And R is18Directly connected with a parent nucleus structure in the compound with the structure shown in the formula (1).
“C3-C6Definition of halocycloalkyl "with" C3-C6Cycloalkyl "is similarly defined, except that C is3-C6At least one H on the ring-forming carbon atoms in the halocycloalkyl group 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 and C2-C6Alkenyl radical, C2-C6Alkynyl, C1-C6Haloalkyl, C2-C6Haloalkenyl, C2-C6Halogenated alkynyl, C1-C4Hydroxyalkyl radical, C1-C4Acylalkyl, C2-C4Alkoxyalkyl group, C2-C6Alkylaminoalkyl, C3-C6Dialkylaminoalkyl, C3-C8Cycloalkylaminoalkyl radical, C2-C6Alkylamino radical, C3-C6Dialkylamino, hydroxyamino, C1-C4Alkoxyamino group, C1-C4Alkoxy radical, C2-C4Alkylcarbonyl group, C1-C4Alkylsulfonyl, aldehyde group, C1-C4Aldoximino, hydroxy, nitro, amino, cyano, halogen, C2-C6Aldoxime ether group, 1, 3-dioxolane group;
R1、R2and R3Each independently selected from H, methyl, ethyl, n-propyl, isopropyl, cyclopropyl, C2-C6Alkenyl radical, C2-C6Alkynyl, C1-C6Haloalkyl, C2-C6Haloalkenyl, C2-C6Halogenated alkynyl, C1-C4Hydroxyalkyl radical, C1-C4Acylalkyl, C2-C4Alkoxyalkyl group, C2-C6Alkylaminoalkyl, C3-C6Dialkylaminoalkyl, C3-C8Cycloalkylaminoalkyl radical, C2-C6Alkylamino radical, C3-C6Dialkylamino, hydroxyamino, C1-C4Alkoxyamino group, C1-C4Alkoxy radical, C2-C4Alkylcarbonyl group, C1-C4Alkylsulfonyl, aldehyde group, aldoximino, hydroxyl, nitro, amino, cyano, fluorine, chlorine, bromine, iodine, C2-C6Aldoxime ether groups and 1, 3-dioxolanyl groups;
R4is 2, 6-difluorophenyl or 2-chloro-6- [ (methylsulfonyl) oxy]A phenyl group.
According to another preferred embodiment, in formula (1),
r is selected from H and methylN-propyl, n-butyl, t-butyl, vinyl, propenyl, ethynyl, propynyl, chloromethyl, dichloromethyl, trichloromethyl, bromomethyl, dibromomethyl, tribromomethyl, fluoromethyl, difluoromethyl, trifluoromethyl, 1-chloroethyl, 2-chloroethyl, 1-fluoroethyl, 2-fluoroethyl, 1-difluoroethyl, 2, 2-difluoroethyl, 1, 2-difluoroethyl, 2,2, 2-trifluoroethyl, 1,2,2, 2-pentafluoroethyl, acetylmethyl, 1-chloro-vinyl, 2, 2-dichlorovinyl, 1-fluoro-vinyl, 2, 2-difluorovinyl, 1, 2-difluorovinyl, fluoroethynyl, chloroethynyl, 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-methylaminoethyl, 2-methylaminoethyl, methylamino-n-propyl, dimethylaminomethyl, 1-dimethylaminoethyl, 2-dimethylaminoethyl, dimethylamino-n-propyl, methyl-ethyl, 2-dimethylaminoethyl, 1-dimethylaminoethyl, 2-dimethylaminoethyl, dimethylamino-n-propyl, methyl-ethyl, methyl-n-propyl, methyl-ethyl, ethyl-propyl, ethyl-ethyl, ethyl-propyl, ethyl-ethyl, ethyl-propyl, ethyl-ethyl, n-propyl, ethyl, n-propyl, ethyl, n-,
Figure BDA0002612930930000031
Methylamino, dimethylamino, methylethylamino, hydroxyamino, methoxyamino, methoxy, ethoxy, acetyl, propionyl, methylsulfonyl, aldehyde, -CH ═ NOH, -CH ═ NOCH3Hydroxy, nitro, amino, cyano, fluoro, bromo or 1, 3-dioxolanyl;
R1、R2and R3Each independently selected from the group consisting of H, methyl, ethyl, n-propyl, isopropyl, cyclopropyl, n-butyl, t-butyl, vinyl, propenyl, ethynyl, propynyl, chloromethyl, dichloromethyl, trichloromethyl, bromomethyl, dibromomethyl, tribromomethyl, fluoromethyl, difluoromethyl, trifluoromethyl, 1-chloroethyl, 2-chloroethyl, 1-fluoroethyl, 2-fluoroethyl, 1-difluoroethyl, 2, 2-difluoroethyl, 1, 2-difluoroethyl, 2,2, 2-trifluoroethyl, 1,2,2, 2-pentafluoroethyl, acetylmethyl, 1-chloro-vinyl, 2, 2-dichlorovinyl, 1-fluoro-vinyl, vinyl chloride, vinyl chloride, vinyl chloride, and vinyl chloride, vinyl chloride, and methyl,2-fluoro-vinyl group, 2-difluorovinyl group, 1, 2-difluorovinyl group, fluoroethynyl group, chloroethynyl group, iodoethynyl group, hydroxymethyl group, 1-hydroxyethyl group, 2-hydroxyethyl group, hydroxy-n-propyl group, methoxymethyl group, 1-methoxyethyl group, 2-methoxyethyl group, 3-methoxy-n-propyl group, ethoxymethyl group, 1-ethoxyethyl group, 2-ethoxyethyl group, 3-ethoxy-n-propyl group, methylaminomethyl group, 1-methylaminoethyl group, 2-methylaminoethyl group, methylamino-n-propyl group, dimethylaminomethyl group, 1-dimethylaminoethyl group, 2-dimethylaminoethyl group, dimethylamino-n-propyl group, methyl-amino-methyl group, 1-dimethylaminoethyl group, 2-dimethylaminoethyl group, dimethylamino-n-propyl group, methyl-ethyl group, 2-diethylamino-ethyl group, methyl-n-propyl group, methyl group, etc,
Figure BDA0002612930930000041
Methylamino, dimethylamino, methylethylamino, hydroxyamino, methoxyamino, methoxy, ethoxy, acetyl, propionyl, methylsulfonyl, aldehyde, -CH ═ NOH, -CH ═ NOCH3Hydroxyl, nitro, amino, cyano, fluoro, chloro, bromo, iodo and 1, 3-dioxolanyl;
R4is 2, 6-difluorophenyl or 2-chloro-6- [ (methylsulfonyl) oxy]A phenyl group.
Particularly preferably, in the formula (1),
r is selected from-CHO and-CH2OH、-CH(OH)CH3、-CH2CH2OH、-CH2OCH3、-CH(CH3)OCH3、-CH2CH2OCH3、-CH＝NOH、-CH＝NOCH3、-CH2NHCH3、-CH2N(CH3)2、
Figure BDA0002612930930000042
-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 or-H;
R1、R2and R3Are all H;
R4is 2, 6-difluorophenyl or 2-chloro-6- [ (methylsulfonyl) oxy]A phenyl group.
Further preferably, in the formula (1),
r is selected from-CHO and-CH2OH、-CH(OH)CH3、-CH2CH2OH、-CH2OCH3、-CH(CH3)OCH3、-CH2CH2OCH3、-CH＝NOH、-CH＝NOCH3、-CH2NHCH3、-CH2N(CH3)2、
Figure BDA0002612930930000043
-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 or-H;
R1、R2and R3Are all H;
R4is 2, 6-difluorophenyl.
In another preferable case, in the formula (1),
r is selected from-CHO and-CH2OH、-CH(OH)CH3、-CH2CH2OH、-CH2OCH3、-CH(CH3)OCH3、-CH2CH2OCH3、-CH＝NOH、-CH＝NOCH3、-CH2NHCH3、-CH2N(CH3)2、
Figure BDA0002612930930000044
-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 or-H;
R1、R2and R3Are all H;
R4is 2-chloro-6- [ (methylsulfonyl) oxy)]A phenyl group.
The present invention is not particularly limited to 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 by combining conventional means in the field of organic synthesis after understanding the technical scheme of the present invention.
The present invention provides, as an example, methods for preparing the aforementioned compounds of the present invention as follows, and those skilled in the art should not be construed as limiting the present invention.
A method for preparing a fused heterocyclic structure-containing compound having a structure represented by formula (1), which comprises: under the condition of nucleophilic substitution reaction, the compound shown in the formula (2-1) and the compound shown in the formula (2-2) are subjected to contact reaction,
Figure BDA0002612930930000051
wherein R in the compound represented by the formula (2-1)4And R, R in the compound represented by the formula (2-2)1、R2、R3The definition of (2) is as defined in R, R in the fused heterocyclic structure-containing compound having the structure represented by the formula (1)1、R2、R3、R4The same definition is applied.
When the nucleophilic substitution reaction of the present invention is carried out under basic conditions, the basic conditions may 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 agent 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, preferably at least one selected from the group consisting of dichloromethane, tetrahydrofuran, N-dimethylformamide, acetonitrile and acetone.
Preferably, the conditions of the contact reaction include: the reaction temperature is 0-60 ℃, and the reaction time is 2-48 h.
In the present invention, the compounds represented by the formulas (2-1) and (2-2) are either commercially available or synthesized according to the structural formula by a method known in the art. The present invention provides methods for preparing the compound represented by formula (2-1) in examples, which are exemplary, and those skilled in the art should not be construed as limiting the present invention.
Preferably, the compound represented by the formula (2-1) and the compound represented by the formula (2-2) are used in a molar ratio of 1: (1-3); more preferably 1: (1.2-2.4).
In the second aspect of the present invention, the product obtained after the contact reaction may be further subjected to a post-treatment process conventionally used in the art to obtain a product with higher purity, for example, the post-treatment operation process comprises: extraction, washing, rotary evaporation, column chromatography, recrystallization and the like, and the present invention is not particularly limited thereto as long as the aforementioned fused heterocyclic structure-containing compound of the present invention can be obtained.
The invention also provides the application of the compound containing the fused heterocyclic structure or the agrochemically acceptable salt, hydrate and solvate thereof in preventing and treating plant oomycete diseases.
Preferably, the plant oomycete disease is a disease caused by at least one pathogen selected from the group consisting of phytophthora infestans, phytophthora sojae, phytophthora capsici, pythium ultimum, phytophthora nicotianae, phytophthora litchi, and peronospora cubensis.
The third aspect of the present invention provides the use of the aforementioned fused heterocyclic structure-containing compound or an agrochemically acceptable salt, hydrate or solvate thereof as an agricultural fungicide.
The fourth aspect of the present invention provides a fungicide, which comprises an active ingredient and an auxiliary material, wherein the active ingredient comprises at least one of the fused heterocyclic structure-containing compound of the structure represented by the aforementioned formula (1) of the present invention or an agrochemically acceptable salt, hydrate, and solvate thereof.
Preferably, the active ingredient is present in an amount of 1 to 99.9 wt%, more preferably 5 to 95 wt%.
Preferably, the bactericide is in a form selected from at least one of emulsifiable concentrate, suspending agent, wettable powder, granule, aqueous agent, poison bait, mother liquor and mother powder.
In the present invention, the adjuvant may be various adjuvants conventionally used in the art, and may be, for example, a surfactant, a solvent, etc.
Experiments show that the compound has excellent control effect on plant diseases caused by various oomycete pathogenic bacteria such as phytophthora infestans, phytophthora capsici, peronophythora litchi, peronospora cubensis and the like, is obviously superior to a conventional oomycete disease control medicament dimethomorph, and has good market development prospect.
The compound provided by the invention can also effectively prevent and control mutant strains which generate resistance to the existing bactericides. Therefore, the compound of the invention has important significance for developing a novel oomycete bactericide without cross resistance.
Detailed Description
The endpoints of the ranges and any values disclosed herein are not limited to the precise range or value, and such ranges or values should be understood to encompass values close to those ranges or values. For ranges of values, between the endpoints of each of the ranges and the individual points, and between the individual points may be combined with each other to give one or more new ranges of values, and these ranges of values should be considered as specifically disclosed herein.
The present invention will be described in detail below by way of examples.
In the following examples, the various starting materials used are commercially available in chemical purity, unless otherwise specified.
Example 1
This example is intended to illustrate the preparation of a compound represented by the formula (2-1). Wherein R in the compound represented by the formula (2-1)4Is 2, 6-difluorophenyl.
Figure BDA0002612930930000061
(1) Adding 1, 3-dichloroacetone (1mol) into 1L of 2M ethyl ether hydrochloride solution at 25 ℃, adding tert-butyl nitrite (1mol), continuing to react for 10 hours at 25 ℃, removing ethyl ether after the reaction is finished, cooling to obtain a crude product of the compound shown in the formula (2-4), washing with 1-chlorobutane, filtering, and collecting a filter cake; and recrystallizing the filtrate, filtering, drying the filter cake to obtain the compound shown in the formula (2-4), and combining the two batches to obtain the pure product of the compound shown in the formula (2-4).
(2) Adding sodium bicarbonate (5mol) into 1L of acetonitrile solution of the compound (1mol) shown in the formula (2-4) at the temperature of 25 ℃, slowly adding 2, 6-difluorostyrene (1mol), continuously stirring for reacting for 4 hours, filtering after the reaction is finished, and removing the solvent in the filtrate to obtain the compound shown in the formula (2-5) which is directly used for the next reaction.
(3) Sequentially adding a compound (1mol) shown in a formula (2-5), 4-aminothiocarbonyltetrahydropyridine-1 (2H) -tert-butyl formate (1.1mol) and sodium bromide (0.1mol) into 2.5L of acetone, heating and refluxing the reaction system for 12H, removing the acetone after the reaction is finished, adding 2L of water, extracting with 500mL of 3 ethyl acetate, combining organic phases, drying and concentrating to obtain a crude product of the compound shown in the formula (2-6), and further performing column chromatography purification by using an elution system formed by silica gel, petroleum ether and ethyl acetate to finally obtain a pure product of the compound shown in the formula (2-6);
(4) the compound represented by the formula (2-6) (0.5mol) was dissolved in 500mL of methanol, 100mL of a hydrogen chloride/methanol solution (4M) was added, the reaction was stirred at 25 ℃ for 6 hours, after completion of the reaction, a 2M aqueous sodium hydroxide solution was slowly added dropwise to adjust the pH to 7, the mixture was extracted with 500mL of 5 ethyl acetate, the organic phases were combined, dried and concentrated to obtain the compound represented by the formula (2-7).
(5) Dripping chloroacetyl chloride (0.15mol) into 500mL of anhydrous dichloromethane solution of a compound (0.1mol) shown in a formula (2-7), keeping the temperature at-5-0 ℃, continuously and slowly adding a potassium carbonate aqueous solution (0.12mol, w/v 20%), keeping the temperature at-5-0 ℃, after finishing dripping, heating to room temperature, after the reaction is finished, separating to remove an aqueous phase, washing an organic phase with saturated saline water, drying with anhydrous sodium sulfate, and concentrating under reduced pressure to obtain a crude compound shown in a formula (2-1), then adding ethyl acetate, stirring into uniform slurry, filtering, and drying a filter cake to obtain a pure compound shown in a formula (2-1).
Example 2
This example is intended to illustrate the preparation of a compound represented by the formula (2-1). Wherein R in the compound represented by the formula (2-1)4Is 2-chloro-6- [ (methylsulfonyl) oxy)]A phenyl group.
Figure BDA0002612930930000071
(1) Slowly dripping methyl magnesium bromide (1.1mol) into an anhydrous tetrahydrofuran solution of 3-chloro-2-vinylphenol (1mol) at 0 ℃ under the protection of nitrogen, after dripping is finished, slowly heating to room temperature, continuing to react for 10 hours, after the reaction is finished, adding saturated ammonium chloride for quenching, extracting with ethyl acetate, drying and concentrating an organic phase to obtain a 3-chloro-2- (1-hydroxyethyl) -phenol crude product, and directly using the crude product in the next reaction;
dissolving the compound 3-chloro-2- (1-hydroxyethyl) -phenol (1mol) in N, N-dimethylacetamide, heating to 160 ℃, slowly adding methanesulfonic acid (1mol), continuously stirring for reacting for 2h, after the reaction is finished, adding 1L of water, extracting with ethyl acetate, washing an organic phase with saturated sodium bicarbonate, and drying and concentrating to obtain a compound 3-chloro-2-vinyl-phenol;
dissolving the compound 3-chloro-2-vinyl-phenol (1mol) in tetrahydrofuran, adding triethylamine (1.2mol), cooling to 0-5 ℃, continuously and slowly adding methanesulfonyl chloride (1.2mol) while keeping the temperature at 0-5 ℃, continuously stirring and reacting for 30min after dropwise adding, adding 250mL of 1N diluted hydrochloric acid after reaction, extracting with ethyl acetate, and drying, filtering and purifying an organic phase by column chromatography to obtain the compound shown in the formula (2-8).
(2) Adding sodium bicarbonate (5mol) into 1L acetonitrile solution of the compound (1mol) shown in the formula (2-4) at 25 ℃, slowly adding the compound (1mol) shown in the formula (2-8), continuously stirring for reacting for 4h, filtering after the reaction is finished, and removing the solvent in the filtrate to obtain the compound shown in the formula (2-9) which is directly used for the next reaction.
(3) Sequentially adding a compound (1mol) shown in a formula (2-9), 4-aminothiocarbonyltetrahydropyridine-1 (2H) -tert-butyl formate (1.1mol) and sodium bromide (0.1mol) into 2.5L of acetone, heating and refluxing the reaction system for 12H, removing the acetone after the reaction is finished, adding 2L of water, extracting with 500mL of 3 ethyl acetate, combining organic phases, drying and concentrating to obtain a crude product of the compound shown in the formula (2-10), and further performing column chromatography purification by using an elution system formed by silica gel, petroleum ether and ethyl acetate to finally obtain a pure product of the compound shown in the formula (2-10);
(4) the compound represented by the formula (2-10) (0.5mol) was dissolved in 500mL of methanol, 100mL of a hydrogen chloride/methanol solution (4M) was added, the reaction was stirred at 25 ℃ for 6 hours, after completion of the reaction, a 2M aqueous sodium hydroxide solution was slowly added dropwise to adjust the pH to 7, the mixture was extracted with 500mL of 5 ethyl acetate, the organic phases were combined, dried and concentrated to obtain the compound represented by the formula (2-11).
(5) Dripping chloroacetyl chloride (0.15mol) into 500mL of anhydrous dichloromethane solution of a compound (0.1mol) shown in a formula (2-11), keeping the temperature at-5-0 ℃, continuously and slowly adding a potassium carbonate aqueous solution (0.12mol, w/v 20%), keeping the temperature at-5-0 ℃, after finishing dripping, heating to room temperature, after the reaction is finished, separating to remove an aqueous phase, washing an organic phase with saturated saline water, drying with anhydrous sodium sulfate, and concentrating under reduced pressure to obtain a crude compound shown in a formula (2-1), then adding ethyl acetate, stirring into uniform slurry, filtering, and drying a filter cake to obtain a pure compound shown in a formula (2-1).
Example 3
This example is for explaining 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), A preparation method of a compound shown in a formula (3-46), a formula (3-47), a formula (3-48), a formula (3-49), a formula (3-50), a formula (3-51), a formula (3-52) and a formula (3-53).
Figure BDA0002612930930000081
Figure BDA0002612930930000091
Figure BDA0002612930930000101
Specifically, the preparation of the compound represented by the formula (3-1) is exemplified
Sodium hydride (1.5mmol) was added to a 10mL solution of 1H-pyrazolo [3,4-b ] pyridine-3-carboxaldehyde (1.2mmol) in anhydrous tetrahydrofuran at 0 ℃ to react for 0.5H, then the compound represented by the formula (2-1) (1mmol) was added thereto, and the reaction was continued at 0 ℃ for 6H. After the reaction is finished, the compound shown in the formula (3-1) is obtained by extraction, washing, concentration and column chromatography purification.
In addition, the preparation of the compounds represented by the formulae (3-36) is exemplified
Sodium hydride (1.5mmol) was added to a 10mL solution of 1H-pyrazolo [3,4-b ] pyridine-3-carboxaldehyde (1.2mmol) in anhydrous tetrahydrofuran at 0 ℃ to react for 0.5H, then the compound represented by the formula (2-1) (1mmol) was added thereto, and the reaction was continued at 0 ℃ for 6H. After the reaction is finished, the compound shown in the formula (3-36) is obtained by extraction, washing, concentration and column chromatography purification.
Formula (3-1): white solid with a yield of 70%, m.p.173-174 ℃,1H NMR(400MHz,CDCl3)δ10.20(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).13C NMR(100MHz,CDCl3) δ 186.79,174.22,174.15,164.05,162.58(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 value C27H22F2N6O2S[M+Na]+559.13344. Found 559.13344.
Formula (3-12): white solid with a yield of 87 percent, m.p.143-145 ℃,1H NMR(600MHz,CDCl3)δ8.50(d,J＝4.8Hz,1H),8.01(d,J＝7.8Hz,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)；13C NMR(150MHz,CDCl3) δ 174.15,164.86,161.65(d, J-4.5 Hz),160.00(d, J-4.5 Hz),151.86,151.15,148.24,144.58,141.25,130.25(t, J-9.1 Hz),129.32,117.76,115.77,115.25(t, J-16.2 Hz),114.96,111.50(d, J-3.0 Hz),111.36(d, J-3.0 Hz),72.37,47.64,44.12,41.45,41.03,39.80,32.00,31.38,12.11 HRMS26H24F2N6O2S[M+H]+523.17223. Found 523.17055.
Formula (3-15): white solid with yield of 78%, m.p.146-147 deg.C,1H NMR(400MHz,DMSO-d6)δ8.72(dd,J＝4.4,1.6Hz,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).13C NMR(100MHz,CDCl3) δ 174.22,163.96,162.55(d, J-8.1 Hz),160.05(d, J-8.1 Hz),152.25,151.06,150.17,145.11,133.72(q, J-39.4 Hz),130.58(t, J-10.1 Hz),129.54,122.58,119.90,118.90,117.92,115.68(t, J-16.2 Hz),112.32,111.93(t, J-6.1 Hz),111.74(t, J-6.1 Hz),72.84,48.99,44.62,41.98,41.51,40.16,32.41,31.74 HRMS calculated value C26H21F5N6O2S[M+Na]+599.12591. Found 599.12602.
Formula (3-17): white solid with a yield of 71 percent, m.p.141-143 ℃,1H NMR(400MHz,CDCl3)8.51(dd,J＝4.8,1.6Hz,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＝12.0Hz,1H),2.19(dd,J＝28.0,13.2Hz,2H),1.88–1.74(m,4H),1.00(t,J＝7.6Hz,3H).13C NMR(100MHz,CDCl3) δ 174.46,173.92,165.21,162.61(d, J-7.1 Hz),160.11(d, J-7.1 Hz),152.29,151.44,148.44,146.04,145.13,130.59(d, J-10.1 Hz),130.17,117.82,116.16,115.77(d, J-16.2 Hz),115.20,111.97(d, J-5.1 Hz),111.78(d, J-6.1 Hz),72.87(t, J-3.0 Hz),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 value C28H28F2N6O2S[M+H]+551.20353. Found 551.20533.
Formula (3-18): white solid with a yield of 88 percent, m.p.138-139 ℃,1H NMR(600MHz,CDCl3)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).13C NMR(150MHz,CDCl3) δ 174.47,165.37,162.27,160.61,152.98,152.36,151.98,148.22,145.21,131.37,130.61,117.77,115.82,113.42,111.99,111.84,72.91,48.43,44.79,41.99,41.64,40.40,34.23,32.52,31.94,30.11 HRMS calcd for C29H30F2N6O2S[M+H]+565.21918. Found 565.21901.
Formula (3-19): white solid with a yield of 90 percent and m.p.155-156 ℃,1H NMR(400MHz,CDCl3)δ8.67(d,J＝7.6Hz,1H),8.57(d,J＝4.4Hz,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＝12.4Hz,1H),2.02–1.76(m,2H).13C NMR(150MHz,CDCl3)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 C27H24F2N6O3S[M+Na]+573.14909. Found 573.14878.
Formula (3-20): white solid, yield 87%, m.p.149-150 deg.C,1H NMR(400MHz,CDCl3)δ8.53(d,J＝4.5Hz,1H),8.26(d,J＝8.0Hz,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).13C NMR(100MHz,CDCl3) δ 174.38,164.91,162.61(d, J-8.1 Hz),160.12(d, J-8.1 Hz),152.29,151.77,148.86,145.15,142.67,130.60(t, J-10.1 Hz),130.56,129.08,117.85,117.61,117.30,115.76(t, J-16.2 Hz),113.80,111.98(d, J-6.1 Hz),111.79(t, J-6.1 Hz),72.87(t, J-3.0 Hz),48.42,44.67,41.99,41.56,40.31,32.50,31.82 HRMS calculated value C27H24F2N6O2S[M+H]+535.17223. Found 535.17301.
Formula (3-23): white solid, yield 89%, m.p.215-217 ℃,1H NMR(400MHz,CDCl3)δ8.55(d,J＝3.6Hz,1H),8.13(d,J＝8.0Hz,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).13C NMR(100MHz,CDCl3)δ174.28,164.44,162.64(d,J＝7.1Hz),160.14(d,J＝7.1Hz),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),81.80,74.79,72.89,48.81,44.69,42.01,41.59,4025,32.48,31.80 HRMS calcd C27H22F2N6O2S[M+H]+533.15658. Found 533.15512.
Formula (3-25): pale yellow solid with a yield of 78%, m.p.131-132 ℃,1H NMR(600MHz,DMSO-d6)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＝13.8Hz,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).13C NMR(100MHz,DMSO-d6) δ 175.11,163.84,162.04(d, J-8.1 Hz),159.56(d, J-8.1 Hz),152.25,151.41,150.87,145.61,144.42,131.53(t, J-10.1 Hz),130.54,121.99,120.15,115.73(t, J-16.2 Hz),112.43(d, J-6.1 Hz),112.24(d, J-6.1 Hz),108.59,72.16,49.87,44.15,41.49,41.26,39.46,32.29,31.86.HRMS calculated value C, m25H21F2N7O4S[M+Na]+576.1236. Found 576.12505.
Formula (3-27): white solid with a yield of 66%, m.p.155-157 ℃,1H NMR(600MHz,CDCl3)δ8.67(dd,J＝8.4,1.6Hz,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＝17.4,9.0Hz,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).13C NMR(100MHz,CDCl3) δ 174.28,164.46,162.49(d, J-8.1 Hz),159.99(d, J-8.1 Hz),152.15,151.53,149.43,145.01,132.20,130.57(t, J-10.1 Hz),118.97,118.05,115.59(t, J-16.2 Hz),114.79,111.93,111.69,72.79,48.80,44.70,41.99,41.41,40.09,32.36,31.71 HRMS calculated value C26H21F2N7O2S[M+H]+566.21443. Found 566.21471.
Formula (3-28): white solid with a yield of 83 percent, m.p.123-124 ℃,1H NMR(600MHz,CDCl3)δ8.58(d,J＝4.8Hz,1H),7.99(d,J＝8.4Hz,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)；13C NMR(150MHz,CDCl3) δ 174.14,164.21,161.82(d, J-7.6 Hz),160.15(d, J-7.6 Hz),152.00,151.07,149.87(d, J-7.6 Hz),144.74,130.38(d, J-10.6 Hz),129.34,119.82,117.87,117.49,115.79,115.38(d, J-15.2 Hz),111.65(d, J-4.5 Hz),111.51(d, J-4.5 Hz),72.52,48.31,44.28,41.64,41.20,39.88,32.13,31.48.HRMS calculated value C25H21BrF2N6O2S[M+Na]+609.04904. Found 609.04743.
Formula (3-29): white solid with a yield of 53%, m.p.120-121 ℃,1H NMR(600MHz,CDCl3)δ8.53(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).13C NMR(100MHz,CDCl3) δ 174.21,164.78,162.31(d, J-8.1 Hz),159.81(d, J-8.1 Hz),152.05,150.59,148.56,144.83,132.85,130.40(t, J-11.1 Hz),130.20,117.81,116.81,115.48,115.47(t, J-16.2 Hz),111.72(d, J-5.1 Hz),111.53(d, J-5.1 Hz),72.59(t, J-3.0 Hz),48.24,44.37,41.66,41.27,40.00,32.22,31.56 HRMS calculated value C25H22F2N6O2S[M+H]+509.15658. Found 509.15668.
Formula (3-30): white solid, yield 82%; m.p.110-111 ℃.1H NMR(600MHz,DMSO-d6)δ8.40(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＝12.0,8.4Hz,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).13C NMR(150MHz,CDCl3) δ 174.16,164.58,162.13,160.51,152.21,151.11,148.95,145.16,132.98,130.52,126.80,120.24,117.75,111.90,111.75,72.83,48.81,44.62,41.94,41.52,40.21,32.44,31.73.HRMS calcd for C25H21BrF2N6O2S[M+Na]+609.04904, found 609.04777.
Formula (3-31): white solid, yield 89%; m.p.143-144 ℃.1H NMR(600MHz,DMSO-d6)δ8.62(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).13C NMR (100MHz, DMSO) δ 175.12,164.77,162.03(d, J is 8.0),159.56(d, J is 8.0),152.25,149.07,144.41,132.58,132.21,131.54(t, J is 10.0),120.12,116.93,115.74(d, J is 16.2),112.43(d, J is 5.0),112.25(d, J is 5.0),112.00,72.16,48.72,44.05,41.36,41.27,32.37,31.90 HRMS calculated C25H21BrF2N6O2S[M+Na]+609.04904, found 609.04935.
Formula (3-32): white solid, yield 92%; m.p.165-166 ℃.1H NMR(600MHz,DMSO-d6)δ8.23(d,J＝4.8Hz,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) δ 175.05,164.70,161.99(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 value C25H21BrF2N6O2S[M+Na]+609.04904, found 609.04888.
Formula (3-33): white solid, yield 86%; m.p.87-88 ℃.1H NMR(600MHz,CDCl3)δ8.67(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).13C NMR(100MHz,CDCl3) δ 174.28,164.46,162.52,162.45,160.02,159.95,152.15,151.53,149.43,145.01,132.20,130.68,130.57,130.47,118.97,118.05,115.75,115.59,115.43,114.79,111.93,111.69,72.79,48.80,44.70,41.99,41.41,40.09,32.36,31.71 HRMS calcd for C26H21F5N6O2S[M+Na]+599.12591, found 599.12602.
Formula (3-34): white solid, yield 92%; m.p.154-155 ℃.1H NMR(600MHz,DMSO-d6)δ8.91(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).13C NMR(100MHz,CDCl3) δ 174.14,164.46,162.59(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 C26H21F5N6O2S[M+Na]+599.12591, found 599.12565.
Formula (3-35): white solid, yield 78%; m.p.128-129 ℃.1H NMR(600MHz,DMSO-d6)δ8.61(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).13C NMR(150MHz,CDCl3) 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 calcd C26H21F5N6O2S[M+Na]+599.12591, found 599.12762.
Formula (3-36): white solid, yield 84%; m.p.161-163 ℃.1H NMR(400MHz,CDCl3)δ9.99(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).13C NMR(100MHz,CDCl3) δ 185.03,174.34,164.78,152.89,148.63,148.36,145.00,144.76,140.09,135.25,130.94,130.29,129.73,129.14,121.26,119.10,118.45,117.44,116.95,45.33,44.90,42.15,41.91,40.19,37.99,32.48,31.79 hrms (esi) calcd for C27H25ClN6O6S2[M+Na]+651.0858, found 651.0832.
Formula (3-37): white solid, yield 83%; m.p.157-158 ℃.1H NMR(400MHz,CDCl3)δ8.52(t,J＝3.6Hz,1H),8.04(d,J＝8.8Hz,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).13C NMR(100MHz,CDCl3)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 C27H27ClN6O5S2[M+Na]+637.1065, found 637.1062.
Formula (3-38): white solid, yield 75%; m.p.148-150 ℃.1H NMR(400MHz,CDCl3)δ8.67(d,J＝4.4Hz,1H),8.24(d,J＝8.0Hz,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).13C NMR(100MHz,CDCl3)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 ═ 5.6Hz),31.78(d, J ═ 5.1Hz), hrms (esi) calculated value C27H24ClF3N6O5S2[M+Na]+691.0782, found 691.0794.
Formula (3-39): white solid, yield 83%; m.p.177-179 ℃.1H NMR(600MHz,CDCl3)δ8.50(d,J＝4.8Hz,1H),8.07(d,J＝7.8Hz,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＝14.4Hz,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).13C NMR(100MHz,CDCl3) δ 182.13,174.69,165.25,152.99,151.56,148.70,148.53,146.04,144.93,135.25,130.23,129.73,129.02,121.27,118.28,116.17,115.15,66.83,59.08,48.32,44.67,42.00,40.38,38.00,32.45,31.88,29.66,22.46,14.08 hrms (esi) calculated value C29H31ClN6O5S2[M+Na]+665.1378, found 665.1383.
Formula (3-40): white solid, yield 80%; m.p.181-183 ℃.1H NMR(400MHz,CDCl3)δ8.55–8.39(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),1.53(d,J＝5.6Hz,9H).13C NMR(100MHz,CDCl3) δ 174.72,165.33,160.00,152.99,151.82,148.69,148.07,144.92,139.33,135.24,131.49,130.24,129.74,129.04,121.28,118.28,117.25,115.79,113.49,59.40,48.45,44.75,42.00,41.28,40.39,38.01,34.20,32.43,31.90,30.08 hrms (esi) calculated value C30H33ClN6O5S2[M+Na]+679.1535, found 679.1537.
Formula (3-41): white solid, yield 46%; m.p.170-172 ℃.1H NMR(400MHz,CDCl3)δ8.56(d,J＝7.2Hz,1H),8.46(d,J＝4.4Hz,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).13C NMR(100MHz,CDCl3)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),114.58,112.30,111.79,73.06,50.49,45.78,42.15,41.87,40.83,37.50,34.59,32.57,28.38.
Formula (3-42): white solid, yield 78%; m.p.166-168 ℃.1H NMR(400MHz,CDCl3)δ8.74(d,J＝4.0Hz,1H),7.76(d,J＝8.4Hz,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(td,J＝11.5,5.4Hz,2H),3.11–2.63(m,1H),2.18(t,J＝15.7Hz,2H),1.81(pd,J＝12.1,4.0Hz,2H).13C NMR(100MHz,CDCl3)δ175.44,166.75,163.70(d,J＝8.4Hz),161.18(d,J＝8.4Hz),155.31,152.82,149.92,146.21,142.95,131.54(t,J＝10.0Hz),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＝4.2Hz),50.39,46.72,42.87,42.60,40.64,38.09,33.89,31.99.
Formula (3-43): white solid, yield 52%; m.p.180-182 ℃.1H NMR(400MHz,CDCl3)δ8.62(d,J＝4.4Hz,1H),8.21(d,J＝8.4Hz,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).13C NMR(100MHz,CDCl3)δ175.33,166.74,163.87(d,J＝7.2Hz),161.25(d,J＝7.2Hz),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%; m.p.178-179 ℃.1H NMR(400MHz,CDCl3)δ8.72(dd,J＝4.4,1.6Hz,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).13C NMR(100MHz,CDCl3) δ 178.65,165.62,157.58,153.78,151.45,147.88,142.26,137.64,135.57,134.25,133.79,132.08,128.06,127.52,124.36,122.97,118.88,115.72,106.51,56.64,49.63,45.47,43.76,37.24,33.68,32.74 hrms (esi) calcd C26H24ClN7O7S2[M+Na]+630.1779, found 630.1792.
Formula (3-45): white solid, yield 48%; m.p.182-184 ℃.1H NMR(400MHz,CDCl3)δ8.66(dd,J＝4.6,1.4Hz,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).13C NMR(100MHz,CDCl3)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%; m.p.169-171 ℃.1H NMR(400MHz,CDCl3)δ8.59(d,J＝4.4Hz,1H),8.00(d,J＝8.0Hz,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).13C NMR(150MHz,CDCl3)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 value C26H24BrClN6O5S2[M+Na]+701.0014, found 701.0015.
Formula (3-47): white solid, yield 75%; m.p.160-162 ℃.1H NMR(600MHz,CDCl3)δ8.53(dd,J＝4.8,1.5Hz,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).13C NMR(150MHz,CDCl3)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%; m.p.166-168 ℃.1H NMR(600MHz,CDCl3)δ8.31(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).13C NMR(150MHz,CDCl3)δ174.38,164.57,152.91,151.13,148.98,148.64,144.93,135.20,133.04,130.18,129.67,128.98,126.83,121.21,120.27,118.23,117.77,48.82,44.63,41.94,40.25,37.93,32.48,32.41,31.78,31.72.
Formula (3-49): white solid, yield 65%; m.p.171-173 ℃.1H NMR(600MHz,CDCl3)δ8.53(d,J＝2.1Hz,1H),8.20(d,J＝2.1Hz,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＝8.2Hz,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＝12.5,6.6Hz,1H).13C NMR(150MHz,CDCl3)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%; m.p.163-165 ℃.1H NMR(600MHz,CDCl3)δ8.41(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).13C NMR(150MHz,CDCl3)δ176.44,166.37,153.81,152.16,149.68,148.56,145.67,136.62,134.26,132.31,130.74,129.51,126.66,123.31,121.19,118.57,118.03,50.62,45.33,42.48,41.37,38.06,33.62,33.32,32.19,31.89.
Formula (3-51): white solid, yield 62%; m.p.163-165 ℃.1H NMR(600MHz,CDCl3)δ8.45(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).13C NMR(150MHz,CDCl3)δ174.40,166.62,154.81,152.06,149.11,148.76,145.86,137.61,134.63,131.20,130.29,129.05,127.74,122.38,121.37,119.64,118.58,50.31,46.52,43.71,41.52,39.26,34.27,34.20,32.59,31.72.
Formula (3-52): white solid, yield 81%; m.p.167-169 ℃.1H NMR(400MHz,CDCl3)δ8.69(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).13C NMR(100MHz,CDCl3) δ 205.86,174.43,164.52,152.95,151.85,148.69,145.99,145.00,135.26,134.13,130.26,129.74,129.07,128.52,122.87,121.27,120.44(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 value C27H24ClF3N6O5S2[M+Na]+691.0782, found 691.0781.
Formula (3-53): white solid, yield 81%; m.p.171-173 ℃.1H NMR(400MHz,CDCl3)δ8.35–8.21(m,2H),7.68(q,J＝3.6Hz,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).13C NMR(100MHz,CDCl3) δ 174.52,164.74,152.99,150.05,148.71,146.91,146.54,144.99,135.27,133.36,131.96,130.26,129.74,129.06,121.28,120.32,118.35,117.36,113.33,59.23,48.29,44.82,42.03,40.33,38.01,32.50,31.84 hrms (esi) calculated value C27H24ClF3N6O5S2[M+Na]+691.0782, found 691.0780.
Example 4
This example is intended to illustrate the production process of the compound represented by the formula (3-2).
Figure BDA0002612930930000171
The compound represented by the formula (3-1) (1.87mmol,1eq) was dissolved in 10mL of anhydrous tetrahydrofuran at 0 ℃ and NaBH was slowly added4(2.80mmol,1.5eq), 3mL of methanol was added dropwise and the temperature was raised to room temperature for 1 h. After the reaction is finished, 20mL of saturated ammonium chloride is added for quenching, 10mL of saturated ammonium chloride is added, the reaction system is extracted by ethyl acetate, and the compound shown in the formula (3-2) is obtained by drying, concentrating and carrying out column chromatography on an organic phase.
Formula (3-2): white solid with a yield of 95 percent, m.p.168-170 ℃,1H NMR(400MHz,DMSO-d6)δ8.51(dd,J＝4.8,1.6Hz,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).13C NMR(100MHz,DMSO-d6) δ 175.11,165.09,162.01(d, J-8.1 Hz),159.53(d, J-8.1 Hz),152.23,151.39,148.62,144.64,144.39,131.49(t, J-11.1 Hz),130.58,120.05,116.54,115.71(t, J-16.2 Hz),113.97,112.40(d, J-6.1 Hz),112.20(d, J-6.1 Hz),72.13,59.55,57.20,48.90,48.09,44.02,41.28(d, J-4.0 Hz),32.39,31.91 HRMS calculated C26H24F2N6O3S[M+H]+539.16714. Found 539.17034.
Example 5
This example is intended to illustrate the production process of the compound represented by the formula (3-3).
Figure BDA0002612930930000181
At 0 ℃, the compound represented by the formula (3-2) (1.00mmol,1eq) was dissolved in 10mL of anhydrous tetrahydrofuran, sodium hydride (1.50mmol,1.5eq) was slowly added, the reaction was continued for 0.5 hour, and methyl iodide (1.20mmol,1.2eq) was added dropwise, and the reaction was completed. And (3) raising the temperature to room temperature, adding 10mL of water, extracting the system by using ethyl acetate, drying an organic phase, concentrating, and carrying out column chromatography to obtain the compound shown in the formula (3-3).
Formula (3-3): white solid, yield 90%, m.p.147-149℃,1H NMR(400MHz,DMSO-d6)δ8.54(dd,J＝4.8,1.6Hz,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＝17.2,8.4Hz,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).13C NMR(100MHz,DMSO-d6) δ 175.11,165.08,161.99(d, J-8.1 Hz),159.51(d, J-8.1 Hz),151.85,151.33,148.55,144.61,142.54,131.44(t, J-11.6 Hz),130.01,123.11,116.51,115.66(t, J-16.2 Hz),114.00,112.38(d, J-6.1 Hz),112.17(d, J-6.1 Hz),72.09,62.35,58.77,57.14,48.88,48.13,43.98,41.25(d, J-4.0 Hz),32.45,32.03 HRMS calculated value C27H26F2N6O3S[M+H]+553.18279. Found 553.18420.
Example 6
This example is intended to illustrate the preparation of the compound represented by the formula (3-4).
Figure BDA0002612930930000182
The compound represented by the formula (3-1) (1.00mmol,1eq) was dissolved in 10mL of anhydrous dichloromethane at room temperature, and thionyl chloride (5.00mmol,5eq) was slowly added thereto, followed by heating and refluxing for 3 hours. After the reaction is finished, pouring the reaction system into 20mL of ice water for quenching, extracting with dichloromethane, drying an organic phase, concentrating, and carrying out column chromatography to obtain the compound shown in the formula (3-4).
Formula (3-4): white solid, yield 85%, m.p.142-143 ℃,1H NMR(400MHz,CDCl3)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).13C NMR(150MHz,CDCl3) δ 174.21,164.61,161.97,160.30,152.06,151.39,149.05,144.90,140.86,130.51,130.09,117.94,117.22,115.52,114.07,111.80,111.66,72.68,48.40,44.57,41.85,41.41,40.08,38.24,32.32,31.63 HRMS calcd for C26H23ClF2N6O2S[M+H]+557.13326. Found 557.13158.
Example 7
This example is intended to illustrate the preparation of the compound represented by the formula (3-5).
Figure BDA0002612930930000191
The compound represented by the formula (3-1) (1.00mmol,1eq) was dissolved in 10mL of anhydrous methanol at room temperature, and hydroxylamine hydrochloride (1.50mmol,1.5eq) and triethylamine (2.00mmol,2.0eq) were added to continue the reaction at room temperature for 5 hours. After the reaction, the reaction system was poured into 20mL of water, extracted with ethyl acetate, and the organic phase was washed with 1N diluted hydrochloric acid and saturated sodium bicarbonate in that order, dried over sodium sulfate, concentrated, and subjected to column chromatography to obtain the compound represented by formula (3-5).
Formula (3-5): white solid with a yield of 91%, m.p.158-159 ℃,1H NMR(600MHz,CDCl3)δ9.34(br s,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) δ 174.37,164.80,162.58(d, J-8.1 Hz),160.08(d, J-8.1 Hz),152.29,151.72,149.35,145.09,141.04,130.60(t, J-10.1 Hz),130.10,117.92,117.35,115.72(t, J-16.2 Hz),114.20,111.97(t, J-6.1 Hz),111.78(t, J-6.1 Hz),72.87(t, J-3.0 Hz),48.39,44.65,41.99,41.54,40.22,38.33,32.45,31.78 HRMS calculated value C26H23F2N7O3S[M+Na]+574.14434. Found 574.14738.
Example 8
This example is intended to illustrate the preparation of the compound represented by the formula (3-6).
Figure BDA0002612930930000192
At 0 ℃, the compound represented by the 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 hour, and methyl iodide (0.60mmol,1.2eq) was added dropwise, and the reaction was completed. And (3) raising the temperature to room temperature, adding 10mL of water, extracting the system by using ethyl acetate, drying an organic phase, concentrating, and carrying out column chromatography to obtain the compound shown in the formula (3-6).
Formula (3-6): white solid, yield 74%, m.p.144-145 ℃,1H NMR(600MHz,CDCl3)δ8.56(d,J＝4.2Hz,1H),8.53(d,J＝7.8Hz,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).13C NMR(100MHz,CDCl3) δ 174.30,164.72,162.69(d, J-8.1 Hz),160.19(d, J-8.1 Hz),152.34,151.83,149.65,145.26,143.90,138.50,132.65,130.65(t, J-10.1 Hz),118.24,117.86,115.83(t, J-16.2 Hz),113.64,112.05(d, J-6.1 Hz),111.85(d, J-6.1 Hz),72.94(t, J-3.0 Hz),62.60,48.61,44.75,42.08,41.63,40.34,32.57,31.86 HRMS27H25F2N7O3S[M+Na]+588.15999. Found 588.16178.
Example 9
This example is intended to illustrate the production processes of the compounds represented by the formulae (3-7), (3-8), (3-9) and (3-10).
Figure BDA0002612930930000201
Specifically, the preparation of the compound represented by the formula (3-7) is exemplified
At room temperature, a compound represented by the formula (3-1) (1.00mmol,1eq), a methylamine solution (1.50mmol,1.50eq,33 wt% ethanol solution) and sodium triacetoxyborohydride (1.50mmol,1.50eq) were sequentially added to 10mL of 1, 2-dichloroethane, stirred for reaction for 5 hours, after the reaction was completed, 20mL of water was added, extraction was performed with dichloromethane, the organic phase was washed with saturated sodium bicarbonate, dried over sodium sulfate, concentrated, and further purified by silica gel column chromatography to obtain a compound represented by the formula (3-7).
Formula (3-7): white solid, yield 75%, m.p.133-135 deg.C,1H NMR(400MHz,CDCl3)δ8.50(d,J＝4.8Hz,1H),8.25(d,J＝8.0Hz,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＝12.4Hz,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).13C NMR(150MHz,CDCl3) δ 174.37,165.07,162.10(d, J-5.1 Hz),160.43(d, J-5.1 Hz),152.20,151.54,149.06,145.04,141.61,130.57(t, J-7.1 Hz),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 value C27H27F2N7O2S[M+H]+552.19878. Found 552.19872.
Formula (3-8): white solid with a yield of 68 percent, m.p.131-132 ℃,1H NMR(400MHz,CDCl3)δ8.46(d,J＝4.8Hz,1H),8.21(d,J＝8.4Hz,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).13C NMR(150MHz,CDCl3)δ174.25,164.81,161.95(d,J＝5.1Hz),16028(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 C28H29F2N7O2S[M+H]+566.21443. Found 566.21471.
Formula (3-9): white solid, yield 77%, m.p.123-125 deg.c,1H NMR(400MHz,CDCl3)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).13C NMR(100MHz,CDCl3) 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-11.1 Hz),129.80,127.31,117.95,117.90,117.37,115.69(t, J-16.2 Hz),111.93(d, J-6.1 Hz),111.74(d, J-6.1 Hz),81.84,74.72,72.81,48.77,44.62,41.96,41.50,40.20,32.44,31.75.HRMS calculated value hrc29H29F2N7O2S[M+H]+578.21443. Found 578.21619.
Formula (3-10): white solid with a yield of 69%, m.p.117-118 ℃,1H NMR(400MHz,CDCl3)δ8.51(d,J＝4.8Hz,1H),8.26(d,J＝8.4Hz,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).13C NMR(150MHz,CDCl3) δ 174.21,164.80,161.89(d, J ═ 6.1Hz),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 C30H31F2N7O2S[M+H]+592.23008. Found value 592.23083.
Example 10
This example is intended to illustrate the preparation of the compounds represented by the formula (3-11).
Figure BDA0002612930930000211
At room temperature, the compound represented by the formula (3-1) (1.00mmol,1eq), ethylene glycol (1.50mmol,1.5eq) and p-toluenesulfonic acid (0.1mmol,0.1eq) were sequentially added to 10mL of chloroform, the mixture was heated to reflux reaction for 6 hours, after the reaction was completed, 20mL of water was added, extraction was performed 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 the formula (3-11).
Formula (3-11): white solid with a yield of 71%, m.p.127-128 ℃,1H NMR(600MHz,CDCl3)δ8.66–8.57(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＝14.4,6.6Hz,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).13C NMR(100MHz,CDCl3) δ 174.20,164.11,162.63(d, J-8.1 Hz),160.13(d, J-8.1 Hz),152.26,150.06,149.13,145.21,142.66,131.73,130.66(d, J-10.1 Hz),120.13,118.00,115.73(d, J-16.2 Hz),113.85,112.01(d, J-6.1 Hz),111.82(d, J-6.1 Hz),100.22,72.93(t, J-3.0 Hz),65.51,63.71,49.16,44.78,42.14,41.55,40.22,32.49,31.77 HRMS calculated value C, x, y28H26F2N6O4S[M+H]+581.17771. Found 581.17399.
Example 11
This example is intended to illustrate the preparation of the compounds represented by the formulae (3-13).
Figure BDA0002612930930000212
The compound represented by the formula (3-2) (1.00mmol,1eq) and diethylaminosulfur trifluoride (1.50mmol,1.5eq) were sequentially added to 10mL of dichloromethane at 0 ℃ and the temperature was raised to room temperature to react for 6 hours, after the reaction was completed, 20mL of water was added and extraction was performed 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 the formula (3-13).
Formula (3-13): white solid, yield 68%, m.p.151-153 ℃,1H NMR(400MHz,CDCl3)δ8.50(d,J＝4.4Hz,1H),8.14(d,J＝8.0Hz,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).13C NMR(150MHz,CDCl3) δ 174.22,164.57,161.92,160.28,152.06,151.35,149.08,144.86,139.83(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 value C26H23F3N6O2S[M+H]+541.16281. Found 541.16508.
Example 12
This example is intended to illustrate the preparation of the compounds represented by the formulae (3-14).
Figure BDA0002612930930000221
The compound represented by the formula (3-1) (1.00mmol,1eq) and diethylaminosulfur trifluoride (1.50mmol,1.5eq) were sequentially added to 10mL of dichloromethane at 0 ℃ and the temperature was raised to room temperature to react for 6 hours, after the reaction was completed, 20mL of water was added and extraction was performed 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 the formula (3-14).
Formula (3-14): white colourSolid with a yield of 70 percent, m.p.157-158 ℃,1H NMR(600MHz,CDCl3)δ8.58(d,J＝4.8Hz,1H),8.26(d,J＝8.4Hz,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).13C NMR(150MHz,CDCl3) δ 174.18,164.44,162.29,160.63,152.32,151.47,149.91,145.31,138.43(t, J ═ 30.2Hz),130.62(t, J ═ 7.1Hz),130.41,118.37,117.81,115.83(t, J ═ 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 C26H22F4N6O2S[M+H]+559.17858. Found 559.17683.
Example 13
This example is intended to illustrate the preparation of the compounds represented by the formulae (3-16).
Figure BDA0002612930930000222
Under the protection of nitrogen, sequentially adding a compound (1.00mmol,1eq) shown in a formula (3-1) and an inner salt (2.0mmol,2.0eq) of (triphenyl phosphonium) difluoroacetic acid into 10mL of anhydrous N, N-dimethylformamide, heating to 60 ℃, reacting for 1h, then adding tetrabutylammonium fluoride (3mL,3.00mmol,3eq and 1M tetrahydrofuran solution), continuously stirring for reacting for 30min, adding 60mL of water after the reaction is finished, extracting with ethyl acetate, washing an organic phase with saturated saline solution, drying with sodium sulfate, concentrating, and further purifying by silica gel column chromatography to obtain the compound shown in the formula (3-16).
Formula (3-16): white solid with a yield of 89%, m.p.142-144 ℃,1H NMR(600MHz,CDCl3)δ8.56(d,J＝4.2Hz,1H),8.09(d,J＝8.4Hz,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).13C NMR(150MHz,CDCl3) δ 174.35,164.92,162.32(d, J ═ 6.1Hz),160.66(d, J ═ 6.1Hz),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 ═ 31.7Hz),32.57,31.90 HRMS calculated value C, C27H23F5N6O2S[M+H]+591.15961. Found 591.15960.
Example 14
Figure BDA0002612930930000231
This example is intended to illustrate the preparation of the compounds represented by the formulae (3-21).
Under the protection of nitrogen, sequentially adding the compound (1.00mmol,1eq) shown in the formula (3-1) and the inner salt (2.0mmol,2.0eq) of (triphenyl phosphonium) difluoroacetic acid into 10mL of anhydrous N, N-dimethylformamide, heating to 80 ℃, reacting for 2h, adding 60mL of water after the reaction is finished, extracting with ethyl acetate, washing an organic phase with saturated saline solution, drying with sodium sulfate, concentrating, and further purifying by silica gel column chromatography to obtain the compound shown in the formula (3-21).
Formula (3-21): white solid with a yield of 65%, m.p.168-169 ℃,1H NMR(600MHz,DMSO-d6)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).13C NMR(100MHz,DMSO-d6)δ175.06,164.82,162.01(d,J＝8.1Hz),159.53(dj8.1 Hz),152.22,151.00,149.19,144.41,133.77(d, J6.1 Hz),133.67(d, J6.1 Hz),131.46(t, J10.1 Hz),130.15(d, J6.1 Hz),120.02,117.25,115.70(t, J16.2 Hz),113.58(d, J3.0 Hz),112.37(d, J6.1 Hz),112.18(d, J6.1 Hz),75.11(d, J14.2 Hz),74.78(d, J14.2 Hz),72.14(t, J3.0 Hz),48.46,44.00,41.28(d, J6.1 Hz),32.34,31.88 HRMS C27H22F4N6O2S[M+H]+571.15338. Found 571.15289.
Example 15
This example is intended to illustrate the preparation of the compounds represented by the formulae (3-22).
Figure BDA0002612930930000232
Under the protection of nitrogen, sequentially adding a compound (1.00mmol,1eq) shown in a formula (3-1) and ethyltriphenylphosphonium bromide (1.2mmol,1.2eq) into 10mL of anhydrous tetrahydrofuran, slowly dropwise adding lithium bis (trimethylsilyl) amide (1.5mL,1.5eq,1M tetrahydrofuran solution) at-15 ℃, heating to room temperature, continuing to react for 2 hours, adding 10mL of saturated ammonium chloride for quenching and 10mL of water, extracting with ethyl acetate, washing an organic phase with saturated saline solution, drying sodium sulfate, concentrating, and further purifying by silica gel column chromatography to obtain the compound shown in the formula (3-22).
Formula (3-22): white solid with a yield of 65%, m.p.119-120 ℃,1H NMR(400MHz,CDCl3)δ8.52(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).13C NMR(100MHz,CDCl3)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 value C28H26F2N6O2S[M+H]+549.18788. Found 549.18675.
Example 16
This example is intended to illustrate the preparation of the compounds of the formulae (3-24).
Figure BDA0002612930930000241
At room temperature, the compound represented by the 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, stirred and reacted for 3 hours, 10mL of ethyl acetate was added after the reaction was completed, the mixture was sequentially washed with 20mL of water and saturated brine, dried over sodium sulfate, concentrated, and further purified by silica gel column chromatography to obtain the compound represented by the formula (3-24).
Formula (3-24): white solid with a yield of 90%, m.p.265-267 ℃,1H NMR(600MHz,CDCl3)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＝14.4Hz,1H),1.90–1.78(m,2H).13C NMR(100MHz,DMSO-d6) 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-10.1 Hz),129.47,126.91,120.34,118.29,116.63,115.55(t, J-16.2 Hz),112.34(d, J-5.1 Hz),112.16(d, J-6.1 Hz),84.12,72.27,48.72,43.99,41.29,41.01,32.30,31.81,23.73.HRMS calculated hrc27H21F2IN6O2S[M+H]+659.05322. Found 659.04904.
Example 17
This example is intended to illustrate the preparation of the compounds represented by the formulae (3-26).
Figure BDA0002612930930000242
The compound represented by the formula (3-25) (1.00mmol,1eq) was dissolved in 10mL of anhydrous methanol at room temperature, Pd/C (50.00mg, 10% by weight) was added, and the reaction system was replaced with hydrogen gas 3 times and the reaction was continued for 12 hours. After the reaction, nitrogen gas was used for 3 times, and the system was filtered and concentrated to obtain a compound represented by the formula (3-26).
Formula (3-26): yellow solid, yield 97%, m.p.142-143 ℃,1H NMR(600MHz,DMSO-d6)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).13C NMR(100MHz,DMSO-d6) δ 175.17,165.68,162.03(d, J-7.1 Hz),159.54(d, J-7.1 Hz),152.25,151.49,148.52,147.67,144.39,131.53(t, J-10.1 Hz),130.03,120.09,115.73(t, J-16.2 Hz),114.08,112.42(d, J-5.1 Hz),112.23(d, J-5.1 Hz),107.27,72.14,47.42,44.05,41.28,32.44,31.95 HRMS calculated value C25H23F2N7O2S[M+H]+524.16748. Found 524.16795.
Test example 1: activity for inhibiting cucumber downy mildew
The testing and investigation method refers to SOP-SC-1098 cucumber downy mildew potting method in disinfectant roll written by KANGZHONG and KUBAOGEN Standard operation Specification for testing biological Activity of pesticides.
TABLE 1
Figure BDA0002612930930000251
90% ≦ a ≦ 100%; b is less than 90% and more than 75%; "-" indicates no test
As can be seen from Table 1, most of the compounds of the present invention have good control effect against cucumber downy mildew. When the administration concentration of the compounds shown in the formulas (3-3), (3-4), (3-6) to (3-13), (3-15), (3-18) to (3-20), (3-23), (3-25), (3-28) and (3-29) is 20mg/L, the control effect on cucumber downy mildew is A grade and reaches more than 90%.
Test example 2: inhibiting oomycete pathogens: in vitro activity of growth of mycelium of Phytophthora capsici, Phytophthora infestans, Phytophthora litchi, Phytophthora sojae and the like
The test method adopts a microplate method to measure the indoor biological activity of the medicament
Peronophythora litchi and Phytophthora sojae: inoculating target bacteria in PDB or V8 liquid culture medium, shaking for 96 hr, filtering, collecting fresh mycelium, weighing 0.1g mycelium, adding into 50mL PDB liquid culture medium, mashing the mycelium with tissue mashing machine into small mycelium segments, making mycelium segment suspension, and standing at 4 deg.C.
Phytophthora infestans: the phytophthora infestans is inoculated on a V8 culture medium plate and cultured for 12 days, after a large amount of sporangia are generated, sterile water is added, the plate is transferred to a refrigerator at 4 ℃ and placed for 1 hour, and then the plate is transferred to room temperature to induce the release of zoospores. After the zoospores are fully released, the concentration of the prepared spores is 105spore/mL spore suspension, at 4 ℃ until use.
The test agent is prepared into 2000mg/L mother liquor by dimethyl sulfoxide, then diluted into 0.1mg/L concentration by sterile water, and placed at 4 ℃ for standby.
Sequentially adding spore suspension (mycelium suspension) and series gradient liquid medicine prepared in advance into each micropore according to the amount of 100 mul +100 mul, placing 96-well micropore plate into an incubator at 25 ℃ (Phytophthora infestans 18 ℃) for static culture, and detecting OD of each treatment by using a microplate reader after 3-4 days (Phytophthora infestans 7 days)595(absorbance at 595 nm) value. Calculating the indoor toxicity of the medicament to the target bacteria. The test results are shown in table 2.
Figure BDA0002612930930000261
TABLE 2
Figure BDA0002612930930000262
95% or more and 100% or less; 90% and B < 95%; 85% to < C < 90%; d is less than 85% and is 75%; e < 75%; "-" indicates no test
As can be seen from Table 2, under the administration concentration of 0.1mg/L, the compounds of the invention have relatively obvious inhibition on the hypha growth of four phytophthora, show as A grade, have an inhibition rate of more than 95 percent, and particularly have great development potential on the activity of phytophthora litchi.
The inhibition effect of 6 compounds shown in the formulas (3-3), (3-12), (3-14), (3-15), (3-20) and (3-29) on the hypha growth of phytophthora sojae is C grade or above, and the inhibition rate is more than 85%; the hypha growth inhibition effect of 5 compounds shown in a formula (3-12), a formula (3-15), a formula (3-20), a formula (3-25), a formula (3-28) and the like on phytophthora capsici is A grade, and the inhibition rate is more than 95%; the inhibition effect of 12 compounds shown in a formula (3-1), a formula (3-3), a formula (3-4), a formula (3-12), a formula (3-13), a formula (3-15), a formula (3-16), a formula (3-19), a formula (3-20), a formula (3-25), a formula (3-28), a formula (3-29) and the like on the hypha growth of phytophthora infestans is grade C or above, and the inhibition rate is more than 85%; the inhibition effect of 10 compounds shown in a formula (3-1), a formula (3-3), a formula (3-4), a formula (3-12), a formula (3-13), a formula (3-14), a formula (3-16), a formula (3-19), a formula (3-20), a formula (3-28) and the like on the hypha growth of phytophthora litchi is grade C or above, and the inhibition rate is more than 85%.
In conclusion, the compounds have great development potential.
The preferred embodiments of the present invention have been described above in detail, but the present invention is not limited thereto. Within the scope of the technical idea of the invention, many simple modifications can be made to the technical solution of the invention, including combinations of various technical features in any other suitable way, and these simple modifications and combinations should also be regarded as the disclosure of the invention, and all fall within the scope of the invention.

Claims (8)

1. A fused heterocyclic structure-containing compound having a structure represented by the formula (1) or an agrochemically acceptable salt thereof,
Figure FDA0003022074860000011
in the formula (1), the reaction mixture is,
r is selected from-CHO and-CH2OH、-CH(OH)CH3、-CH2CH2OH、-CH2OCH3、-CH(CH3)OCH3、-CH2CH2OCH3、-CH＝NOH、-CH＝NOCH3、-CH2NHCH3、-CH2N(CH3)2、
Figure FDA0003022074860000012
-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 or-H;
R1、R2and R3Are all H;
R4is 2, 6-difluorophenyl or 2-chloro-6- [ (methylsulfonyl) oxy]A phenyl group.
2. The use of the fused heterocyclic structure-containing compound according to claim 1 or an agrochemically acceptable salt thereof for controlling plant oomycete diseases.
3. The use according to claim 2, wherein the plant oomycete disease is selected from the group consisting of diseases caused by at least one of phytophthora infestans, phytophthora sojae, phytophthora capsici, peronophythora litchi, and peronospora cubensis.
4. Use of the fused heterocyclic structure-containing compound according to claim 1 or an agrochemically acceptable salt thereof as a fungicide for agricultural chemicals.
5. A fungicide which consists of an active ingredient and an auxiliary material, wherein the active ingredient comprises at least one of a fused heterocyclic structure-containing compound having a structure represented by the formula (1) of claim 1 or an agrochemically acceptable salt thereof.
6. The bactericide as claimed in claim 5, wherein the content of said active ingredient is 1 to 99.9% by weight.
7. The bactericide according to claim 6, wherein the bactericide is in a form selected from at least one of emulsifiable concentrate, suspension, powder, granule, aqueous agent, poison bait, mother liquor and mother powder.
8. The bactericide according to claim 7, wherein the bactericide is in the form of wettable powder.
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CN103180317A (en) * 2010-08-25 2013-06-26 拜耳知识产权有限责任公司 Heteroarylpiperidine and -piperazine derivatives as fungicides
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