CN115572282A - Pyrazole amide compound containing aromatic heterocyclic structure, and preparation method and application thereof - Google Patents

Pyrazole amide compound containing aromatic heterocyclic structure, and preparation method and application thereof Download PDF

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CN115572282A
CN115572282A CN202110757318.4A CN202110757318A CN115572282A CN 115572282 A CN115572282 A CN 115572282A CN 202110757318 A CN202110757318 A CN 202110757318A CN 115572282 A CN115572282 A CN 115572282A
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CN115572282B (en
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李忠
邵旭升
徐晓勇
程家高
张露
陈睿嘉
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East China University of Science and Technology
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • 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
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
    • 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
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/58—1,2-Diazines; Hydrogenated 1,2-diazines
    • 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
    • A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
    • A01N43/707—1,2,3- or 1,2,4-triazines; Hydrogenated 1,2,3- or 1,2,4-triazines
    • 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
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/80—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,2
    • 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
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/88—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms six-membered rings with three ring hetero atoms
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

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Abstract

The invention relates to a pyrazole amide compound containing an aromatic heterocyclic structure, and a preparation method and application thereof. Specifically, the invention discloses a structure shown in formula (I), wherein the definition of each group and substituent is described in the specification; the invention also discloses a preparation method of the compound and application of the compound in the aspects of killing insects and mites.

Description

Pyrazole amide compound containing aromatic heterocyclic structure and preparation method and application thereof
Technical Field
The invention relates to the technical field of agricultural chemicals and preparation thereof, in particular to a pyrazole amide compound containing an aromatic heterocyclic structure and a preparation method and application thereof.
Background
The 5-amidopyrazole insecticide is a medicament with high efficiency, wide insecticidal spectrum, wide application range and excellent effect, and has the functions of killing insects, inhibiting food, inhibiting spawning and sterilizing. The compounds act on a respiratory chain complex I to inhibit the transmission of electrons, the electron transmission is blocked, an electrochemical (proton) gradient cannot be established, ATP synthesis cannot be driven, ATP supply is insufficient, and insects, mites, bacteria and fungi die.
Disclosure of Invention
The invention aims to provide a pyrazole amide compound containing an aromatic heterocyclic structure shown in a formula I, a preparation method thereof and application thereof in the aspect of disinsection.
The invention provides a pyrazole amide compound containing an aromatic heterocyclic structure, an optical isomer, a cis-trans isomer or an agriculturally and pharmaceutically acceptable salt thereof, which is characterized in that the compound has a structure shown in a formula I,
Figure BDA0003148260290000011
wherein,
R 1 selected from the group consisting of substituted or unsubstituted:C 1-6 alkyl radical, C 3-6 Cycloalkyl, C 2-6 Alkenyl radical, C 2-6 Alkynyl, C 1-8 Alkoxy, hydrogen, phenyl, naphthalenyl, 5-6 membered heteroaryl, amino, hydroxyl, amido, acyloxy, carboxymethyl, nitro, cyano, sulfonic, halogen, formyl, acyl, carboxyl; by substituted is meant substituted with one or more (e.g., 2,3,4, or 5) substituents selected from the group consisting of: halogen, hydroxy, C 1-6 Alkoxy radical, C 1-6 Alkyl, amino, nitro, carboxyl, carboxymethyl, cyano, C 1-6 Haloalkyl, amido, acyloxy, C 3-6 Cycloalkyl radical, C 3-6 Halogenocycloalkyl, C 2-6 Alkenyl radical, C 2-6 Haloalkenyl, C 2-6 Alkynyl, C 2-6 Halogenated alkynyl, C 5-7 A cycloalkenyl group;
R 2 selected from the group consisting of substituted or unsubstituted: c 1-6 Alkyl radical, C 3-6 Cycloalkyl radical, C 2-6 Alkenyl radical, C 2-6 Alkynyl, C 1-6 Alkoxy, phenyl, hydrogen, amino, hydroxyl, amide, acyloxy, carboxymethyl, nitro, cyano, sulfonic, halogen, formyl, acyl, carboxyl; the substitution refers to substitution by one or more halogens;
a is selected from substituted or unsubstituted phenyl, substituted or unsubstituted naphthalene cyclyl, substituted or unsubstituted 4-8 membered heteroaryl, substituted or unsubstituted C 8-14 A heteroaromatic bicyclic or tricyclic ring system; by substituted is meant substituted with one or more (e.g., 2,3,4, or 5) substituents selected from the group consisting of: halogen, hydroxy, C 1-6 Alkoxy radical, C 1-6 Alkyl, amino, nitro, carboxyl, carboxymethyl, cyano, C 1-6 Haloalkyl, amido, acyloxy, C 3-6 Cycloalkyl radical, C 3-6 Halogenocycloalkyl, C 2-6 Alkenyl radical, C 2-6 Halogenated alkenyl group, C 2-6 Alkynyl, C 2-6 Halogenated alkynyl, C 5-7 Cycloalkenyl, phenyl, naphthyl;
b is an unsaturated or saturated 5-6 membered nitrogen containing heterocyclic group, wherein said heterocyclic group contains at least one N heteroatom and 0-2 heteroatoms selected from N, O or S;
n is selected from 0 or 1;
y is selected from the group consisting of: hydrogen, C 1-6 Alkoxy radical, C 1-8 Alkyl radical, C 1-6 Haloalkyl, C 3-6 Cycloalkyl radical, C 3-6 Halogenocycloalkyl, C 2-6 Alkenyl radical, C 2-6 Halogenated alkenyl group, C 2-6 Alkynyl, C 2-6 Halogenated alkynyl, C 5-7 Cycloalkenyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthalenylcyclyl, substituted or unsubstituted 4-8 membered heteroaryl, substituted or unsubstituted C 8-14 A heteroaromatic bicyclic or tricyclic ring system, or a 3-7 membered heterocyclyl; by substituted is meant substituted with one or more (e.g., 2,3,4, or 5) substituents selected from the group consisting of: c 1-6 Alkyl radical, C 2-6 Alkenyl, halogen, C 1-6 Haloalkyl, cyano, amino, nitro, carboxyl, carboxymethyl, amido, acyloxy, C 3-6 Cycloalkyl radical, C 3-6 Halogenocycloalkyl, C 2-6 Haloalkenyl, C 2-6 Alkynyl, C 2-6 Halogenated alkynyl, C 5-7 Cycloalkenyl, phenyl, naphthyl.
In another preferred embodiment, R 1 Selected from the group consisting of substituted or unsubstituted: c 1-6 Alkyl radical, C 2-6 Alkenyl radical, C 1-6 Alkoxy, phenyl, 5-6 membered heteroaryl, hydrogen, amino, amido, halogen, formyl, acyl, carboxy; said substitution means substitution with one or more (e.g. 2,3,4 or 5) substituents selected from the group consisting of: halogen, hydroxy, C 1-6 Alkoxy radical, C 1-6 Alkyl, amino, nitro, carboxyl, carboxymethyl, cyano, C 1-6 Haloalkyl, amide, acyloxy;
R 2 selected from the group consisting of substituted or unsubstituted: c 1-5 Alkyl radical, C 3-5 Cycloalkyl radical, C 2-5 Alkenyl radical, C 2-6 Alkynyl, C 1-6 Alkoxy, halogen; the substitution refers to substitution by one or more halogens;
a is selected from substituted or unsubstituted phenyl, substituted or unsubstituted 4-8 membered heteroaryl; the substitution means substitution by one or more substituents selected from the group consisting of: halogen, hydroxy, C 1-6 Alkoxy radical, C 1-6 Alkyl, amino, nitro, carboxyl, carboxymethyl, cyano, C 1-6 Haloalkyl, amido, acyloxy, C 3-6 Cycloalkyl radical, C 3-6 Halocycloalkyl radical, C 2-6 Alkenyl radical, C 2-6 Haloalkenyl, C 2-6 Alkynyl, C 2-6 Halogenated alkynyl, C 5-7 Cycloalkenyl, phenyl, naphthyl;
b is an unsaturated 5-6 membered nitrogen containing heterocyclyl wherein said heterocyclyl contains at least one N heteroatom and 0-2 heteroatoms selected from N, O or S;
y is selected from the group consisting of: hydrogen, C 1-6 Alkoxy radical, C 1-6 Alkyl radical, C 1-6 Haloalkyl, C 3-6 Cycloalkyl, C 2-6 Alkenyl radical, C 2-6 Alkynyl, substituted or unsubstituted phenyl, substituted or unsubstituted 4-8 membered heteroaryl; the substitution means substitution with one or more substituents selected from the group consisting of: c 1-6 Alkyl radical, C 2-6 Alkenyl, halogen, C 1-6 Haloalkyl, cyano, amino, nitro, carboxyl, carboxymethyl, amido, acyloxy, C 3-6 Cycloalkyl, C 3-6 Halogenocycloalkyl, C 2-6 Haloalkenyl, C 2-6 Alkynyl, C 2-6 Halogenated alkynyl, C 5-7 Cycloalkenyl, phenyl, naphthyl.
In another preferred embodiment, B is a 5-or 6-membered nitrogen-containing heterocyclic group containing 1-3N heteroatoms and 0-2S heteroatoms in the ring.
In another preferred embodiment, B is a compound containing 1-3 oxo (= O), thioxo (= S), or dioxy (e.g. having two oxo groups on S, forming S (O) 2 ) A substituted nitrogen-containing heterocyclic group.
In another preferred embodiment, B is a 5-6 membered nitrogen containing heterocyclyl, wherein said heterocyclyl contains 1,2 or 3N heteroatoms and 0-2 heteroatoms selected from N, O or S, and the number of ring heteroatoms in said heterocyclyl is 3 or less (i.e., 1,2, 3).
In another preferred embodiment, said 3-7 membered heterocyclyl contains 1-3 heteroatoms selected from N, O and S.
In another preferred embodiment, B is through the ring N atom with- (CH) 2 ) n Y being linked, i.e. forming
Figure BDA0003148260290000031
In another preferred embodiment, B is selected from the group consisting of:
Figure BDA0003148260290000032
Figure BDA0003148260290000041
in another preferred embodiment, R 1 Selected from the group consisting of substituted or unsubstituted: c 1-6 Alkyl, phenyl, 5-6 membered heteroaryl, hydrogen, amino, amido, halo; the substitution means substitution with one or more substituents selected from the group consisting of: halogen, hydroxy, C 1-6 Alkoxy radical, C 1-6 Alkyl, amino, nitro, carboxyl;
R 2 selected from the group consisting of substituted or unsubstituted: c 1-5 Alkyl radical, C 1-6 Alkoxy radical, C 2-5 Alkenyl, halogen; the substitution refers to substitution by one or more halogens;
a is selected from substituted or unsubstituted phenyl; the substitution means substitution with one or more substituents selected from the group consisting of: halogen, hydroxy, C 1-6 Alkoxy radical, C 1-6 Alkyl, amino, nitro, carboxyl, cyano, C 1-6 Haloalkyl, amide, acyloxy;
b is selected from the following group:
Figure BDA0003148260290000042
y is selected from the group consisting of: hydrogen, C 1-6 Alkoxy radical, C 1-6 Alkyl radical, C 1-6 Haloalkyl, C 2-6 Alkenyl, substituted or unsubstituted phenyl, substituted or unsubstituted 4-8 membered heteroaryl; the substitution means substitution with one or more substituents selected from the group consisting of: c 1-6 Alkyl radical, C 2-6 Alkenyl, halogen, C 1-6 Haloalkyl, cyano, amino, nitro, carboxyl, carboxymethyl, amido, acyloxy.
In another preferred embodiment, R 1 Selected from the group consisting of substituted or unsubstituted: c 1-6 Alkyl, phenyl, 5-6 membered heteroaryl; the substitution means substitution with one or more substituents selected from the group consisting of: halogen, hydroxy, C 1-6 Alkoxy radical, C 1-6 Alkyl, amino, nitro, carboxyl;
R 2 selected from the group consisting of substituted or unsubstituted: c 1-5 Alkyl, halogen; said substitution refers to substitution by one or more halogens;
y is selected from the group consisting of: hydrogen, C 1-6 Alkyl radical, C 1-6 Haloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted 4-8 membered heteroaryl; the substitution means substitution with one or more substituents selected from the group consisting of: c 1-6 Alkyl radical, C 2-6 Alkenyl, halogen, C 1-6 Haloalkyl, cyano, amino, nitro, carboxyl, carboxymethyl, amido, acyloxy.
In another preferred embodiment, R 1 Selected from the group consisting of substituted or unsubstituted: c 1-5 Alkyl, phenyl, pyridyl; said substitution refers to substitution by one or more halogens;
R 2 selected from halogen and C 1-5 A haloalkyl group.
In another preferred embodiment, R 1 Selected from the group consisting of substituted or unsubstituted: c 1-5 Alkyl radical, C 3-6 Cycloalkyl radical, C 2-5 Alkenyl radical, C 2-5 Alkynyl, C 1-4 An alkoxy group; the substitution means substitution with one or more substituents selected from the group consisting of: halogen, hydroxy, C 1-6 Alkoxy radical, C 1-6 Alkyl, amino, nitro, carboxyl, carboxymethyl, cyano, C 1-6 Haloalkyl, amido, acyloxy.
In another preferred embodiment, R 1 Selected from the group consisting of substituted or unsubstituted: phenyl, 5-6 membered heteroaryl, hydrogen, amino, nitro, cyano, sulfonic acid, halogen(ii) a The substitution refers to substitution by one or more halogens.
In another preferred embodiment, R is 1 Is a substituted phenyl ring or a substituted 5-6 membered heteroaryl.
In another preferred embodiment, R is 1 Is a halogenated benzene ring or a halogenated 5-6 membered heteroaryl.
In another preferred embodiment, the 5-6 membered heteroaryl is a 6 membered heteroaryl containing 1-2N heteroatoms, preferably pyridinyl.
In another preferred embodiment, the 5-6 membered heteroaryl is pyridyl, preferably with the N atom of the ring of the pyridyl in the ortho position.
In another preferred embodiment, R 1 Selected from the group consisting of:
Figure BDA0003148260290000051
methyl, methyl,
Figure BDA0003148260290000052
In another preferred embodiment, C is 1-6 The alkyl group is a methyl group.
In another preferred embodiment, the 5-6 membered heteroaryl is substituted with a halogen, such as: 2-chloropyridine.
In another preferred embodiment, R 2 Selected from the group consisting of substituted or unsubstituted: c 1-6 Alkyl radical, C 3-6 Cycloalkyl radical, C 2-6 Alkenyl, phenyl, hydrogen, amino, hydroxyl, amido, nitro, cyano, halogen; the substitution refers to substitution by one or more halogens.
In another preferred embodiment, C is 1-6 Alkyl is halo-substituted, such as difluoromethyl.
In another preferred embodiment, the halogen is Br.
In another preferred embodiment, R 2 Selected from Br or difluoromethyl.
In another preferred embodiment, a is selected from the group consisting of substituted or unsubstituted: phenyl, pyridyl, pyrimidinyl, pyrazolyl, furanyl, thienyl, pyrrolyl; the substitution is selected from one or moreSubstituent group substitution: halogen, hydroxy, C 1-6 Alkoxy radical, C 1-6 Alkyl radical, C 3-6 Cycloalkyl, C 2-6 Alkenyl radical, C 2-6 Alkynyl, halo C 1-6 Alkyl, amino, nitro.
In another preferred embodiment, Y is selected from the group consisting of: hydrogen, C1-6 alkoxy, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, substituted or unsubstituted phenyl, substituted or unsubstituted 4-8 membered heteroaryl; the substitution refers to substitution by one or more substituents selected from the group consisting of: c1-6 alkyl, C2-6 alkenyl, halogen, C1-6 haloalkyl, cyano, amino, nitro, carboxyl, carboxymethyl, amido, acyloxy.
In another preferred embodiment, Y is selected from the group consisting of: hydrogen, C1-6 alkyl, C1-6 haloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted 4-8 membered heteroaryl; the substitution means substitution with one or more substituents selected from the group consisting of: c1-6 alkyl, halogen, C1-6 haloalkyl, cyano, amino, nitro, carboxyl.
In another preferred embodiment, Y is a substituted or unsubstituted group selected from phenyl, pyridyl, pyrazolyl, furyl, thienyl, pyrrolyl; the substitution means substitution with one or more substituents selected from the group consisting of: halogen, hydroxy, C 1-6 Alkoxy radical, C 1-6 Alkyl radical, C 3-6 Cycloalkyl, C 2-6 Alkenyl radical, C 2-6 Alkynyl, halo C 1-6 Alkyl, amino, nitro.
In another preferred embodiment, Y is selected from the group consisting of: CH (CH) 3 、CH 2 CH 3 、CH 2 CF 3 、CH 2 CH 2 CH 3 、CH 2 CH 2 CF 3 、CH(CH 3 ) 2 、CH 2 CH 2 CH 2 CH 3 、CH 2 CH(CH 3 ) 2 、CH 2 CH 2 CH 2 CH 2 CH 3 、CH 2 CH(CH 3 )CH 2 CH 3 、CH 2 C(CH 3 ) 3 。
In another preferred embodiment, B is selected from the group consisting of:
Figure BDA0003148260290000061
in another preferred embodiment, a is selected from the group consisting of:
Figure BDA0003148260290000062
in another preferred embodiment, ring A, ring B, R1, R2 and Y are each independently the corresponding groups in compounds 1-423.
In another preferred embodiment, said compound of formula I is selected from compounds 1 to 423 in table 1.
In another preferred embodiment, the compound is selected from the following numbered compounds in table 1: 1.2, 3,4, 5,13, 14,15, 16, 17, 18, 19, 20, 21, 22, 23, 38, 39, 45, 49, 52, 61, 65, 66, 68, 70, 71, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 309, 310, 311, 312, 313, 314, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 340, 341, 342, 343, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396.
In a second aspect of the present invention, there is provided a pesticidal composition comprising:
1) 0.001 to 99.99% by weight of a compound of claim 1, an optical isomer, a cis-trans isomer, or an agriculturally pharmaceutically acceptable salt thereof, or a combination thereof; and
2) An agriculturally pharmaceutically acceptable carrier and/or excipient.
In a third aspect of the present invention, there is provided a use of the compound of claim 1, an optical isomer, a cis-trans isomer, or an agriculturally pharmaceutically acceptable salt thereof for controlling lepidopteran pests; or for preparing insecticides and/or acaricides for controlling lepidopteran pests.
In another preferred example, the pests are armyworm and diamondback moth.
In a fourth aspect of the invention, there is provided a method of combating and/or killing pests which comprises applying to a plant suffering from a pest infestation, the soil surrounding or to the environment a compound according to claims 1 to 7 or an agriculturally acceptable salt thereof or a pesticidal composition according to claim 8.
In another preferred embodiment, the aromatic heterocyclic structure-containing pyrazole amide compound or the agriculturally and pharmaceutically acceptable salt thereof or the pesticide composition is applied at a concentration of 0.05 to 200ppm; preferably, 0.1 to 100ppm; more preferably, it is 0.5 to 50ppm.
It is to be understood that within the scope of the present invention, the above-described features of the present invention and those specifically described below (e.g., in the examples) may be combined with each other to form new or preferred embodiments. Not to be reiterated herein, but to the extent of space.
Detailed Description
The inventor of the invention has long and intensive research and discovers and synthesizes a series of pyrazole amide compounds containing aromatic heterocyclic structures, which have novel structures and remarkable insecticidal effects. On this basis, the inventors have completed the present invention.
Term(s) for
In the present invention, unless otherwise specified, the terms used have the ordinary meaning known to those skilled in the art.
The term "C 1-6 Alkyl "means a straight or branched chain alkyl group having 1 to 6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl orLike groups.
The term "C 2-6 The alkenyl group "means a straight-chain or branched alkenyl group having 2 to 6 carbon atoms, such as vinyl, allyl, 1-propenyl, isopropenyl, 1-butenyl, 2-butenyl or the like.
The term "C 2-6 Alkynyl "means a straight or branched chain alkynyl group having 2 to 6 carbon atoms, such as ethynyl, propynyl or the like.
The term "C 3-6 Cycloalkyl "refers to a cyclic alkyl group having 3 to 6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or the like.
The term "C 5-7 Cycloalkenyl "means a cyclic alkenyl group having 5 to 7 carbon atoms with one or more double bonds, such as cyclopentenyl, cyclohexenyl, cycloheptenyl, 1, 3-cyclohexadienyl, 1, 4-cyclohexadienyl or the like.
As used herein, the term "C 1-8 Alkoxy "means a straight or branched chain alkoxy group having 1 to 8 carbon atoms, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy or the like.
The term "halogen" refers to fluorine, chlorine, bromine, or iodine. The term "halogenated" refers to a group substituted with one or more of the above halogen atoms, which may be the same or different, such as trifluoromethyl, pentafluoroethyl, heptafluoroisopropyl, or the like.
The term "heterocycle" means that at least one of the atoms forming the skeleton of the heterocycle is not carbon, and is nitrogen, oxygen or sulfur. Typically, the heterocyclic ring contains no more than 4 nitrogens, no more than 2 oxygens, and/or no more than 2 sulfurs. Unless otherwise indicated, the heterocyclic ring may be a saturated, partially unsaturated, or fully unsaturated ring.
The term "alkyl" refers to a group of an alkane molecule lacking one hydrogen atom; the term "alkylene" refers to a group of an alkane molecule lacking two hydrogen atoms. Similarly, "alkenylene", "alkynylene", "cycloalkylene", "cycloalkenylene", "phenylene", "naphthylene", "heterocyclylene" or "heteroarylene bicyclic or tricyclic ring system" are defined analogously.
The term "aryl" denotes a hydrocarbyl moiety comprising one or more aromatic rings. For example, the term "C 6-10 Aryl "refers to an aromatic ring group having 6 to 10 carbon atoms, such as phenyl, naphthyl, and the like, which does not contain heteroatoms in the ring.
The term "heteroaryl" denotes a heteroaromatic system containing 1 to 4 heteroatoms including nitrogen, oxygen and S (O) r (where r is an integer 0,1, 2), e.g., 4-8 membered heteroaryl refers to a heteroaromatic system containing 4-8 ring atoms, 4-10 membered heteroaryl refers to a heteroaromatic system containing 4-10 ring atoms, including but not limited to pyrrolyl, furanyl, thienyl, pyrazolyl, thiazolyl, imidazolyl, oxazolyl, isoxazolyl, pyridyl, pyranyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzimidazolyl, triazolyl, and the like.
Unless specifically stated to be "substituted or unsubstituted", the groups of the present invention may be substituted with a substituent selected from the group consisting of: halogen, acyloxy, cyano, amino, nitro, carboxyl, amido, carboxymethyl, C 1-6 Alkyl radical, C 1-6 Alkoxy radical, C 1-6 Haloalkyl, C 2-6 Alkenyl radical, C 2-6 Halogenated alkenyl group, C 2-6 Alkynyl, C 2-6 Halogenated alkynyl, hydroxy, C 3-6 Cycloalkyl radical, C 3-6 Halocycloalkyl, hydroxy C 1-4 Alkyl radical, C 5-7 Cycloalkenyl, phenyl, naphthyl, and the like.
The inert solvent refers to various solvents which do not react with the raw materials, including various straight, branched or cyclic alcohols, ethers or ketones, alkyl halides, 1, 4-dioxane, acetonitrile, tetrahydrofuran, N, N-Dimethylformamide (DMF), dimethyl sulfoxide (DMSO), etc.
The term "agriculturally pharmaceutically acceptable salt" means that the anion of the salt is known and acceptable in forming a pharmaceutically acceptable salt of the nematicide. Preferably, the salt is water soluble. Suitably, the acid addition salts formed by the compounds of formula (I) include salts formed with inorganic acids, such as hydrochlorides, phosphates, sulphates, nitrates; and salts formed with organic acids such as acetates, benzoates, and the like.
The term "optical isomer" means that the chiral carbon atom involved in the compound of the present invention may be in the R configuration, or may be in the S configuration, or a combination thereof. The compounds of the invention may contain one or more asymmetric centers and thus occur as racemates, racemic mixtures, single enantiomers, diastereomeric compounds and individual diastereomers. Asymmetric centers that may be present depend on the nature of the various substituents on the molecule. Each such asymmetric center will independently produce two optical isomers and all possible optical isomers and diastereomeric mixtures and pure or partially pure compounds are included within the scope of the invention. The present invention includes all isomeric forms of the compounds.
Process for the preparation of the compounds of the invention
The compound represented by the general formula of the present invention can be produced by the following method, however, the conditions of the method, such as reactants, solvent, base, amount of the compound used, reaction temperature, time required for the reaction, etc., are not limited to the following explanation. The compounds of the present invention may also be conveniently prepared by optionally combining various synthetic methods described in the present specification or known in the art, and such combinations may be readily carried out by those skilled in the art to which the present invention pertains. Reagents may be purchased commercially if feasible.
Typical embodiments of the compounds of the present invention may be synthesized using the following general reaction schemes. It is clear from the description given herein that the general scheme can be modified by substituting other materials with similar structures to obtain correspondingly different products. Synthetic methods can be used as needed to provide large scale production. The starting materials can be obtained commercially or synthesized using published methods. The examples given herein, through simple testing procedures, the characteristics of the final product often make the characteristics of the necessary starting materials apparent.
Synthesis reaction parameters the compounds of the present invention may be prepared from readily available starting materials using, for example, the following general methods and procedures. It will be appreciated that where typical or optimized process conditions (i.e., reaction temperatures, times, molar ratios of reactants, solvents, catalysts, pressures, etc.) are given, other process conditions may also be used, unless otherwise indicated. Optimal reaction conditions may vary with the particular reactants or solvents used, but such conditions may be determined by one skilled in the art by routine optimization procedures.
The starting materials for the following reactions are generally known compounds or can be prepared by known procedures or obvious modifications thereof. For example, many of the starting materials are available from commercial suppliers, others may be prepared by procedures described in the text of standard references or obvious modifications.
In the production process of the present invention, each reaction is usually carried out in an inert solvent at a reaction temperature of-20 to 120 ℃ (preferably 50 to 100 ℃ or 120 to 180 ℃). The reaction time is usually 2 to 24 hours, preferably 4 to 18 hours, and the reaction time can be appropriately extended according to the reaction requirement, and the specific reaction time is determined according to the degree of reaction.
Typically, bases used in the reactions of the present invention include (but are not limited to): triethylamine, diisopropylethylamine, diethylamine, piperidine, piperazine, morpholine, N-methylmorpholine, triethylenediamine (DABCO), 1, 8-diazabicyclo [5.4.0] undec-7-ene (DBU), 1, 5-diazabicyclo [4.3.0] non-5-ene (DBN), potassium carbonate, potassium bicarbonate, sodium carbonate, sodium bicarbonate, cesium carbonate, sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide, or a combination thereof.
The invention provides a preparation method of the pyrazole amide compound containing the aromatic heterocyclic structure, which comprises the following steps:
heating and refluxing the compound Z1 and the compound Z2 under an alkaline condition to react to obtain a compound 3; reducing nitro on the compound 3 to obtain a compound 4; heating and refluxing the compound 4 and the compound 5 for reaction to obtain a final compound, namely the pyrazole amide compound containing the aromatic heterocyclic structure.
Wherein, the compound 1 has the following structural formula:
Figure BDA0003148260290000111
the structural formula of the compound 2 is as follows:
Figure BDA0003148260290000112
the structural formula of the compound 3 is as follows:
Figure BDA0003148260290000113
the structural formula of the compound 4 is as follows:
Figure BDA0003148260290000114
the structural formula of the compound 5 is as follows:
Figure BDA0003148260290000115
the structural formula of the final compound is as follows:
Figure BDA0003148260290000116
A. b, n and Y are defined as the same as the above.
In another preferred embodiment, the preparation method of the invention comprises the following steps:
the method comprises the following steps: compound 1 was added to an eggplant-shaped bottle, and DMF was added to the eggplant-shaped bottle to dissolve it. Sequentially adding the compound 2 and triethylamine, heating to 90 ℃, and carrying out reflux reaction for 5 hours. The mixture was then poured into ice water and a precipitate precipitated out. The resulting precipitate was separated by filtration, washed with excess water and dried at 70-75 deg.C to give a crude product which was purified by ethanol recrystallization to give compound 3.
Step two: adding compound 3, iron powder, ammonium chloride, ethanol and water (E) into eggplant-shaped bottle t OH:H 2 O = 2.5. Heated to 75 ℃ and refluxed for 0.5h. Filtering with diatomite to obtain filtrate. And (4) removing ethanol and water by rotary evaporation to obtain a solid. Separating and purifying by column chromatography (eluent: 5-10% methanol/dichloromethane), and evaporating the solvent to obtain a compound 4.
Step three: adding compound 4, compound 5, N-methylimidazole and N, N, N ', N' -tetramethyl chlorourea hexafluorophosphate into an eggplant-shaped bottle, and dissolving the mixture in acetonitrile. Heating to 60 ℃, refluxing for 6h, and detecting the completion of the reaction by TLC. The mixture was poured into water and a precipitate precipitated out. The precipitate was filtered and washed with excess water to give a crude solid. Separating and purifying by column chromatography (eluent: 15% -25% methanol/dichloromethane), evaporating the solvent to dryness to obtain the final product, namely the pyrazole amide compound containing aromatic heterocyclic structure,
in the production process of the present invention, each reaction is usually carried out in an inert solvent at a reaction temperature of-20 to 120 ℃ (preferably 50 to 100 ℃ or 120 to 180 ℃). The reaction time is usually 2 to 24 hours, preferably 4 to 18 hours, and the reaction time can be appropriately extended according to the reaction requirement, and the specific reaction time is determined according to the degree of the reaction.
The inert gas includes at least one of nitrogen, helium, neon, or argon.
Bases used in the reaction include (but are not limited to): triethylamine, diisopropylethylamine, diethylamine, piperidine, piperazine, morpholine, N-methylmorpholine, triethylenediamine (DABCO), 1, 8-diazabicyclo [5.4.0] undec-7-ene (DBU), 1, 5-diazabicyclo [4.3.0] non-5-ene (DBN), potassium carbonate, potassium bicarbonate, sodium carbonate, sodium bicarbonate, cesium carbonate, sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide, or a combination thereof.
Composition comprising a metal oxide and a metal oxide
The active substances according to the invention can be prepared in a customary manner to give pesticide compositions. These active compounds can be formulated in the customary formulations, for example as solutions, emulsions, suspensions, powders, foams, pastes, granules, aerosols, natural and synthetic materials impregnated with active substance, microcapsules in polymers, coating compositions for seeds, and formulations for use with combustion devices, for example smoking cartridges, smoking pots and smoking trays, and ULV Cold mist (Cold mist) and hot mist (Warm mist) formulations.
These formulations can be produced in a known manner, for example by mixing the active compounds with extenders, that is liquid or liquefied gas or solid diluents or carriers, and optionally with surfactants, that is emulsifiers and/or dispersants and/or foam formers. Organic solvents may also be used as adjuvants, for example when water is used as extender.
When liquid solvents are used as diluents or carriers, it is basically suitable, for example: aromatic hydrocarbons such as xylene, toluene or alkylnaphthalene; chlorinated aromatic or chlorinated aliphatic hydrocarbons, such as chlorobenzene, vinyl chloride or dichloromethane; aliphatic hydrocarbons, such as cyclohexane or paraffins, for example mineral oil fractions; alcohols, such as ethanol or ethylene glycol and their ethers and lipids; ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone; or less commonly used polar solvents such as dimethylformamide and dimethylsulfoxide, and water.
Liquid gas diluents or carriers refer to liquids that will become gases at normal temperature and pressure, such as aerosol propellants, such as halogenated hydrocarbons, as well as butane, propane, nitrogen, and carbon dioxide.
The solid carrier may be a finely divided natural mineral such as kaolin, clay, talc, quartz, attapulgite, montmorillonite or diatomaceous earth; and ground synthetic minerals such as highly dispersed silicic acid, alumina and silicates. Solid carriers for granules are crushed and classified natural zircon, such as calcite, marble, pumice, sepiolite and dolomite, as well as synthetic granules of inorganic and organic coarse powders, and granules of organic materials, such as sawdust, coconut shells, corn cobs and tobacco stalks, and the like.
Nonionic and anionic emulsifying trains may be used as emulsifiers and/or foam formers. Such as polyoxyethylene-fatty acid esters, polyoxyethylene-fatty alcohol ethers, such as alkylaryl polyethylene glycol ethers, alkyl sulfonates, alkyl sulfates, aryl sulfonates and albumin hydrolysates. The dispersant comprises lignin sulfite waste liquor and methyl cellulose.
Binders such as carboxymethylcellulose and natural and synthetic polymers in the form of powders, granules or emulsions, for example gum arabic, polyvinyl alcohol and polyvinyl acetate, can be used in the formulations.
Colorants such as inorganic dyes, e.g., iron oxide, cobalt oxide, and prussian blue; organic dyes such as azo dyes or metal phthalocyanine dyes; and with trace nutrients such as salts of iron, manganese, boron, copper, cobalt, aluminum, and zinc, and the like.
The active compounds according to the invention can be present in their commercial preparations in a mixture with other active compounds, such as insecticides, fungicides, herbicides, growth regulators, etc., or in the use forms prepared from these preparations. Insecticides include, for example, phosphates, carbamates, pyrethroids, chlorinated hydrocarbons, substances produced by microorganisms, and the like, fungicides include strobilurins, amides, triazoles, and the like, and miticides include quinoxalines, amidines, organosulfurs, organotins, thiazines, and the like.
Furthermore, the active compounds according to the invention can also be present in their commercial preparations in a mixture with synergists, i.e. compounds which increase the activity of the compounds, which are not necessarily added, since the active compounds themselves are active.
These formulations generally contain from 0.001 to 99.99% by weight, preferably from 0.01 to 99.9% by weight, more preferably from 0.05 to 90% by weight, of the active compound according to the invention, based on the total weight of the nematicide composition. The concentration of the active compound in the commercial preparations or dosage forms used can vary within wide limits. The concentration of active compound in the dosage form to be used can be from 0.0000001 to 100% (g/v), preferably between 0.0001 and 1% (g/v).
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In addition, any methods and materials similar or equivalent to those described herein can be used in the methods of the present invention. The preferred embodiments and materials described herein are intended to be exemplary only.
Compared with the prior art, the invention has the following main advantages:
the compound has excellent insecticidal activity and can be used for controlling lepidoptera pests, particularly armyworms and diamondback moths.
The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. Experimental procedures without specific conditions noted in the following examples, generally according to conventional conditions, or according to conditions recommended by the manufacturer. Unless otherwise indicated, percentages and parts are by weight.
Examples
Example 1 preparation of N- (2-ethyl-1, 3-dioxo-5-isoindolyl) -3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carboxamide
Step 1: synthesis of 2-ethyl-5-nitroisoindoline-1, 3-dione
Figure BDA0003148260290000141
In a 100mL eggplant type bottle, 5-nitrophthalimide (10.00 mmol) was added, 40mL of N, N-dimethylformamide was added to dissolve, and bromoethane (20.00 mmol) and triethylamine (TEA, 30.00 mmol) were added to the eggplant type bottle in this order. The reaction mixture was then poured into ice water and the precipitate precipitated out after heating to 90 ℃ and refluxing for 5h. Filtering and separating to obtain precipitate, washing the precipitate with excessive water, drying at 70-75 ℃, and recrystallizing and purifying the obtained crude product with ethanol to obtain 2.00g of white solid compound with the yield of 91%.
Step 2: synthesis of 2-ethyl-5-aminoisoindoline-1, 3-dione
Figure BDA0003148260290000151
2-Ethyl-5-nitroisoindoline-1, 3-dione (8 mmol) obtained in step 1, iron powder (40 mmol) and ammonium chloride (24 mmol) were added to a 100mL eggplant-shaped flask, and 30mL ethanol and 12mL water were added to dissolve. Heating to 75 deg.C, reflux reacting for 0.5h, filtering with diatomite, and collecting filtrate. Ethanol and water were removed by rotary evaporation to give a solid, which was purified by column chromatography (eluent: 10% methanol/dichloromethane), and the solvent was evaporated to dryness to give 1.22g of a yellow solid product in 80.5% yield.
And step 3: synthesis of N- (2-ethyl-1, 3-dioxo-5-isoindolyl) -3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carboxamide
Figure BDA0003148260290000152
In a 100mL round-bottom flask, 2-ethyl-5-aminoisoindoline-1, 3-dione (5 mmol) obtained in step 2, 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid (10 mmol), N-methylimidazole (35 mmol), and N, N, N ', N' -tetramethylchlorourea hexafluorophosphate (12 mmol) were added and dissolved in 40mL acetonitrile. Heating to 60 ℃, refluxing for 6h, and detecting the completion of the reaction by TLC. The reaction mixture was poured into water and a precipitate precipitated out. Filtering and separating to obtain precipitate, and washing the precipitate with excessive water to obtain solid crude product. Separation and purification by column chromatography (eluent: 20% methanol/dichloromethane) and evaporation of the solvent afforded the product as a white solid, 1.21g, 51% yield.
The final test results were as follows: 1 H NMR(400MHz,DMSO)δ11.05(s,1H),8.55-8.54(m,1H),8.27-8.25(m,1H),8.12(d,J＝1.7Hz,1H),7.98-7.96(m,1H),7.84(d,J＝8.2Hz,1H),7.69-7.66(m,1H),7.51(s,1H),3.65-3.52(m,2H),1.14(t,J＝7.1Hz,3H). 13 c NMR (101MHz, DMSO). Delta.167.25, 167.20,155.97,148.09,147.28,143.24,139.62,139.02,133.06,127.64,126.86,126.83,126.62,124.42,124.11,113.75,111.42,32.37,13.60 HRMS (ESI-TOF) molecular formula C 19 H 13 BrClN 5 O 3 :
[M-H] - Calculated relative molecular mass:471.9818, found 471.9809.
Example 2: preparation of N- (2- (2-fluoroethyl) -1, 3-dioxo-5-isoindolyl) -3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carboxamide
Figure BDA0003148260290000161
A synthesis similar to that of example 1 was used, except that:
the raw material bromoethane in the step 1 adopts 1-bromo-2-fluoroethane.
The final test results were as follows: 1 H NMR(400MHz,DMSO)δ11.07(s,1H),8.56-8.54(m,1H),8.27-8.24(m,1H),8.14(d,J＝0.9Hz,1H),8.00-7.98(m,1H),7.87(d,J＝8.2Hz,1H),7.69-7.65(m,1H),7.53(s,1H),4.42(m,2H),3,83(t,2H). 13 C NMR(101MHz,DMSO)δ167.23,166.85,155.87,148.69,147.18,143.44,139.52,139.12,133.03,127.94,126.76,126.63,126.42,124.72,124.01,113.55,111.42,60.26,44.01. 19 f NMR (376 MHz, DMSO) delta-60.02 HRMS (ESI-TOF) with a molecular formula of C 19 H 12 BrClFN 5 O:[M-H] - Calculated relative molecular mass: 489.9723, found 489.9725.
Example 3: preparation of N- (2- (4-methylbenzyl) -1, 3-dioxo-5-isoindolyl) -3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carboxamide
Figure BDA0003148260290000162
A synthesis similar to that of example 1 was used, except that:
example 1 the starting material, ethyl bromide in step 1, was 4-methylbenzyl bromide.
The final test results were as follows: 1 H NMR(400MHz,DMSO)δ11.07(s,1H),8.56-8.54(m,1H),8.27-8.24(m,1H),8.14(d,J＝0.9Hz,1H),8.00-7.98(m,1H),7.87(d,J＝8.2Hz,1H),7.69-7.66(m,1H),7.51(s,1H),7.18(d,J＝8.0Hz,2H),7.12(d,J＝7.9Hz,2H),4.69(s,2H),2.25(s,3H). 13 C NMR(101MHz,DMSO)δ167.22,167.13155.99,148.09,147.27,143.44,139.61,139.01,136.58,133.65,132.89,129.07,127.63,127.38,126.85,126.81,126.41,124.62,124.38,113.95,111.45,40.64,20.60 HRMS (ESI-TOF) molecular formula C 25 H 17 BrClN 5 O 3 :[M-H] - Calculated relative molecular mass: 548.0131, found 548.0130.
Example 4: preparation of N- (2-methylfuranyl-1, 3-dioxo-5-isoindolyl) -3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carboxamide
Step 1
Figure BDA0003148260290000171
5-Nitrophthalic anhydride (10.00 mmol) was added to a 100mL eggplant type bottle, and dissolved in 8mL of glacial acetic acid. Then 2-furanmethanamine (12.00 mmol) is dropped into an eggplant-shaped bottle, heated to 110 ℃, and refluxed for 18h. The reaction mixture was poured into ice water to precipitate. The precipitate is isolated by filtration, washed with excess water and dried at 70-75 ℃. The obtained crude product was purified by recrystallization from ethanol to obtain 2.20g of a white solid compound with a yield of 81%.
Step 2, synthesis of N- (2-methylfuryl) -5-aminoisoindoline-1, 3-dione
Figure BDA0003148260290000172
The N-2- (furyl-2-methyl) -5-nitroisoindoline-1, 3-dione (5 mmol) obtained in step 1, iron powder (25 mmol) and ammonium chloride (15 mmol) were added to a 100mL eggplant-type bottle, and 20mL ethanol and 8mL water were added to dissolve. Heating to 75 deg.C, reflux reacting for 0.5h, filtering with diatomite, and collecting filtrate. Ethanol and water were removed by rotary evaporation to give a crude solid product which was purified by column chromatography (eluent: 10% methanol/dichloromethane) and the solvent was evaporated to dryness to give 1.03g of a yellow solid product in 85% yield.
Step 3 Synthesis of N- (2-methylfuranyl-1, 3-dioxo-5-isoindolyl) -3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carboxamide
Figure BDA0003148260290000181
In a 100mL round-bottom flask, N-2- (furyl-2-methyl) -5-aminoisoindoline-1, 3-dione (4 mmol) obtained in step 2, 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid (8 mmol), N-methylimidazole (28 mmol), and N, N, N ', N' -tetramethylchlorourea hexafluorophosphate (9.6 mmol) were charged, and dissolved in 20mL of acetonitrile. Heating to 60 ℃, refluxing for 6h, and detecting the completion of the reaction by TLC. The reaction mixture was poured into water and a precipitate precipitated out. Filtering and separating to obtain precipitate, and washing the precipitate with excessive water to obtain a solid crude product. Separation and purification by column chromatography (eluent: 22% methanol/dichloromethane) and evaporation of the solvent afforded the product as a white solid, 1.07g, 51% yield.
The final test results were as follows: 1 H NMR(400MHz,DMSO)δ11.09(s,1H),8.56-8.54(m,1H),8.27-8.25(m,1H),8.15(d,J＝1.7Hz,1H),8.01-7.99(m,1H),7.88(d,J＝8.2Hz,1H),7.70-7.66(m,1H),7.56(d,J＝1.0Hz,1H),7.52(s,1H),6.40-6.39(m,1H),6.36(d,J＝3.1Hz,1H),4.74(s,2H). 13 c NMR (101MHz, DMSO). Delta.166.75, 166.65,155.99,149.32,148.06,147.30,143.48,142.64,139.64,138.97,132.79,127.63,126.89,126.84,126.29,124.66,124.48,113.93,111.47,110.61,108.06,34.12 HRMS (ESI-TOF) molecular formula C 22 H 13 BrClN 5 O 4 :[M-H] - Calculated relative molecular mass: 523.9767, found 523.9770.
Example 5: preparation of N- (4-methylpyridyl-1, 3-dioxo-5-isoindolyl) -3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carboxamide
A synthesis similar to that of example 4 was used, except that:
example 4 the starting material, 2-furanmethanamine, in step 1, was 4-pyridinemethanamine.
The final test results were as follows: 1 H NMR(400MHz,DMSO)δ11.10(s,1H),8.56-8.54(m,1H),8.28-8.25(m,1H),8.16(d,J＝1.6Hz,1H),8.01-7.99(m,1H),7.88(d,J＝8.2Hz,1H),7.70-7.67(m,1H),7.52(s,1H),7.44-7.42(m,2H),7.09-7.05(m,2H),4.91(s,2H). 13 c NMR (101MHz, DMSO). Delta.166.75, 166.65,156.00,148.06,147.30,143.52,139.63,138.97,138.58,132.76,127.62,127.01,126.92,126.88,126.84,126.24,126.09,124.69,124.53,113.97,111.48,109.25,35.60 HRMS (ESI-TOF) molecular formula C 23 H 14 BrClN 6 O 3 :[M-H] - Calculated relative molecular mass: 534.9927, found 534.9928.
Example 6: preparation of N- (2-chlorophenyl-1, 3-dioxo-5-isoindolyl) -3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carboxamide
Figure BDA0003148260290000191
A synthesis similar to that of example 4 was used, except that:
example 4 in step 1, 2-chloroaniline was used as the starting material, 2-furanmethanamine.
The final test results were as follows: 1 H NMR(400MHz,DMSO)δ11.08(s,1H),8.58-8.54(m,1H),8.26-8.25(m,1H),8.18(d,J＝1.6Hz,1H),8.01-7.97(m,1H),7.88(d,J＝8.2Hz,1H),7.70-7.67(m,1H),7.52(s,1H),7.48-7.45(m,1H),7.44-7.42(m,1H),7.09-7.05(m,1H),6.97-6.95(m,1H). 13 c NMR (101MHz, DMSO). Delta.166.72, 166.65,156.00,148.06,147.30,143.52,139.63,138.97,138.58,132.76,127.62,127.01,126.92,126.88,126.84,126.24,126.09,124.69,124.53,113.97,111.48,110.98,110.52 HRMS (ESI-TOF) molecular formula C 23 H 12 BrCl 2 N 5 O 3 :[M-H] - Calculated relative molecular mass: 553.9428, found 553.9426.
Example 7: preparation of N- (2-benzyl-1, 3-dioxo-5-isoindolyl) -3-bromo-1- (2-chlorophenyl) -1H-pyrazole-5-carboxamide
Figure BDA0003148260290000192
A synthesis similar to that of example 1 was used, except that:
example 1 the starting material, ethyl bromide in step 1, was benzyl bromide; in the step 3, 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid is used as the raw material, and 3-bromo-1- (3-chloro-2-phenyl) -1H-pyrazole-5-carboxylic acid is used as the raw material.
The final test results were as follows: 1 H NMR(400MHz,DMSO)δ10.99(s,1H),8.16(d,J＝0.8Hz,1H),8.02(d,J＝1.2Hz,1H),7.85(d,J＝8.2Hz,1H),7.65-7.61(m,2H),7.58-7.52(m,2H),7.48(s,1H),7.40(m,1H),7.36-7.33(m,2H),7.15-7.11(t,J＝8.8Hz,2H),4.72(s,2H). 13 c NMR (101MHz, DMSO). Delta.165.89, 164.57,162.80,161.62,143.34,139.08,134.57,132.20,131.83,130.81,130.62,130.54,129.40,128.51,128.40,127.72, 127.13.87, 126.05,123.91,119.90,115.28,113.25,109.35,44.52 HRMS (ESI-TOF) of formula C 25 H 16 BrClN 4 O 3 :[M-H] - Calculated relative molecular mass: 533.0022, found 533.0023.
Example 8: preparation of N- (2- (3-cyanobenzyl) -1, 3-dioxo-5-isoindolyl) -3-difluoromethyl-1-methyl-1H-pyrazole-5-carboxamide
A synthesis similar to that of example 1 was used, except that:
example 1 the starting material, ethyl bromide in step 1, was 3-cyanobenzyl bromide; in the step 3, 3-difluoromethyl-1-methyl-1H-pyrazole-5-carboxylic acid is adopted as the raw material 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid.
The final test results were as follows: 1 H NMR(400MHz,DMSO)δ10.58(s,1H),8.55(s,1H),8.30(d,J＝1.6Hz,1H),8.07-8.04(m,1H),7.89(d,J＝8.2Hz,1H),7.40-7.31(m,1H),7.19-7.14(m,2H),6.78(s,1H),6.49(s,1H),4.74(s,2H),3.99(s,3H). 19 FNMR(376MHz,DMSO)δ-113.48. 13 c NMR (101MHz, DMSO). Delta.168.66, 167.53,166.72,165.43,162.81,161.67,155.82,143.32,139.76,137.12,132.25,131.80,130.62,128.57,126.05,123.90,119.92,115.20,109.65,99.97,44.52,38.55 HRMS (ESI-TOF) formula C 22 H 15 F 2 N 5 O 3 :[M-H] - Calculated relative molecular mass: 434.1070, found 434.1071.
Example 9: preparation of N- (3-methylphenyl-1, 3-dioxo-5-isoindolyl) -3-difluoromethyl-1- (5-bromo-2-pyridinyl) -1H-pyrazole-5-carboxamide
Figure BDA0003148260290000201
A synthesis similar to that of example 1 was used, except that:
example 1 in step 1, ethyl bromide was used as the starting material, 3-methylbenzyl bromide was used.
The final test results were as follows: 1 H NMR(400MHz,DMSO)δ11.10(s,1H),8.56-8.54(m,1H),8.28-8.25(m,1H),8.16(d,J＝1.6Hz,1H),8.01-7.99(m,1H),7.88(d,J＝8.2Hz,1H),7.70-7.67(m,1H),7.52(s,1H),7.44-7.42(m,1H),7.09-7.05(m,1H),6.97-6.95(m,1H),6.88(s,1H),6.38(s,1H),2.99(s,3H). 19 F NMR(376MHz,DMSO)δ-110.29. 13 c NMR (101MHz, DMSO) delta 166.75,166.65,156.00,148.06,147.30,143.52,139.63,138.97,138.58,136.74,134.82,132.76,127.62,127.01,126.92,126.88,126.84,126.24,126.09,124.69,124.53, 118.66.97, 111.48,35.60 HRMS (ESI-TOF) has the formula C 25 H 16 BrF 2 N 5 O 3 :[M-H] - Calculated relative molecular mass: 551.0410, found 551.0408.
Example 10: preparation of 3-bromo-1- (3-chloro-2-pyridinyl) -N- (4-oxo-3, 4-dihydro-5-benzo [ d ] [1,2,3] triazinyl) -1H-pyrazole-5-carboxamide
Step 1 Synthesis of 5-Nitro-2H-benzo [ d ] [1,3] oxazine-2, 4 (1H) -dione
Figure BDA0003148260290000211
2-amino-6-nitrobenzoic acid (40 mmol) was added to tetrahydrofuran (120 mL), stirred, and cooled to-10 ℃. Triphosgene (40 mmol) was dissolved in tetrahydrofuran (20 mL), the temperature was controlled between-10 ℃ and-5 ℃, and the solution was added dropwise slowly over 1 hour. Slowly warm up and reflux. After the reaction is finished, the solvent is evaporated under reduced pressure, anhydrous ether (150 mL) is added into the residue, the mixture is fully stirred and filtered, and a filter cake is washed by the anhydrous ether and dried to obtain a solid product 7,32g, wherein the yield is more than 88%.
Step 2
Figure BDA0003148260290000212
5-Nitro-2H-benzo [ d ] [1,3] oxazine-2, 4 (1H) -dione (35 mmol) and ammonium carbonate (70 mmol) were added to 1, 4-dioxane (100 mL) and stirred to give a suspension. The reaction was heated to 60 ℃ and the progress of the reaction was followed by TLC. After the reaction, the reaction mixture was cooled to room temperature, and the solvent was evaporated under reduced pressure. To the residue was added water (150 mL), extracted with ethyl acetate (60 mL. Times.3), the organic phases combined, washed with saturated aqueous sodium bicarbonate solution, dried over anhydrous sodium sulfate, filtered, and the filtrate concentrated to give 5.38g of a solid product with a yield of 85% or more.
Step 3 Synthesis of 5-nitrobenzo [ d ] [1,2,3] triazin-4 (3H) -one
Figure BDA0003148260290000221
Dissolving 2-amino-6-nitrobenzamide (30 mmol) in 0.5M hydrochloric acid (240 mL), stirring under the condition of ice salt bath (controlling the temperature between 0 and 5 ℃), slowly dropwise adding an aqueous solution containing sodium nitrite (60 mmol), after dropwise adding for about 40 minutes, naturally heating to room temperature and continuing to react for 2 to 3 hours. Adjusting pH to 7-8 with sodium hydroxide water solution, stirring for 15 min, vacuum filtering, washing filter cake with water, and drying to obtain solid product 4.90g with yield over 85%.
Step 4 Synthesis of 5-aminobenzo [ d ] [1,2,3] triazin-4 (3H) -one
Figure BDA0003148260290000222
To a 100mL eggplant-type bottle were added 5-nitrobenzo [ d ] [1,2,3] triazin-4 (3H) -one (10 mmol), iron powder (50 mmol), ammonium chloride (30 mmol), 20mL of ethanol and 8mL of water were added to dissolve. Heating to 75 deg.C, reflux reacting for 0.5h, filtering with diatomite, and collecting filtrate. Removing ethanol and water from the filtrate by rotary evaporation to obtain solid, separating and purifying by column chromatography (eluent: 8% methanol/dichloromethane), and evaporating the solvent to obtain yellow solid product 1.22g with yield over 75%.
Step 5 Synthesis of 3-bromo-1- (3-chloro-2-pyridinyl) -N- (4-oxo-3, 4-dihydro-5-benzo [ d ] [1,2,3] triazinyl) -1H-pyrazole-5-carboxamide
Figure BDA0003148260290000223
A100 mL round-bottomed flask was charged with 5-aminobenzo [ d ] [1,2,3] triazin-4 (3H) -one (7 mmol), 3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carboxylic acid (14 mmol), N-methylimidazole (49 mmol), N, N, N ', N' -tetramethylchlorourea hexafluorophosphate (16.8 mmol), and dissolved in 40mL acetonitrile. The reaction was heated to 60 ℃ and refluxed for 6h, and the completion of the reaction was monitored by TLC. The mixture was poured into water and a precipitate precipitated out. Filtering, washing with excessive water to obtain solid, separating and purifying by column chromatography (eluent: 20% methanol/dichloromethane), and evaporating solvent to obtain final white solid product 1.60g with yield over 51%.
The final test results were as follows: 1 H NMR(400MHz,DMSO)δ15.32(s,1H),12.58(s,1H),8.58(d,J＝1.4Hz,1H),8.56(d,J＝3.6Hz,1H),8.28(d,J＝8.1Hz,1H),8.01-7.97(m,1H),7.89(d,J＝8.1Hz,1H),7.73-7.69(m,1H),7.27(s,1H). 13 CNMR (101MHz, DMSO) delta 155.97,155.49,148.14,147.29,141.22,140.80,139.61,138.96,129.15,127.69,127.00,126.87,126.85,121.06,112.90,111.45 HRMS (ESI-TOF) with molecular formula C 16 H 8 BrClN 7 O 2 :[M-H] - Calculated relative molecular mass: 443.9617, found 443.9621.
Example 11: preparation of 3-bromo-1- (3-chloro-2-pyridinyl) -N- (3-ethyl-4-oxo-3, 4-dihydro-5-benzo [ d ] [1,2,3] triazinyl) -1H-pyrazole-5-carboxamide
Figure BDA0003148260290000231
A synthesis similar to that of example 10 was used, except that:
example 10 step 4 ethyl followed by reduction was performed as in step 1 of example 1.
The final test results were as follows: 1 H NMR(400MHz,DMSO)δ11.18(s,1H),8.58(d,J＝1.4Hz,1H),8.56(d,J＝3.6Hz,1H),8.27(d,J＝8.1,1.4Hz,1H),8.25-8.22(m,1H),8.18(d,J＝8.9Hz,1H),7.71-7.67(m,1H),7.56(s,1H),4.39(q,J＝7.2Hz,2H),1.38(t,J＝7.2Hz,3H). 13 c NMR (101MHz, DMSO). Delta.156.00, 154.41,148.12,147.30,141.50,140.41,139.63,138.95,129.23,127.67,126.88,126.87,120.16,113.06,111.49,44.44,13.91 HRMS (ESI-TOF) molecular formula C 18 H 13 BrClN 7 O 2 :[M-H] - Calculated relative molecular mass: 471.9930, found 471.9925.
Example 12: preparation of 3-bromo-1- (3-chloro-2-pyridinyl) -N- (3- (3-fluorophenyl) -4-oxo-3, 4-dihydro-5-benzo [ d ] [1,2,3] triazinyl) -1H-pyrazole-5-carboxamide
Figure BDA0003148260290000241
A synthesis similar to that of example 10 was used, except that:
example 10 step 4 was followed by 3-fluorobenzyl and reduction as in step 1 of example 1.
The final test results were as follows: 1 H NMR(400MHz,DMSO)δ12.49(s,1H),8.61(d,J＝8.1Hz,1H),8.55(d,J＝4.4Hz,1H),8.27(d,J＝7.8Hz,1H),8.04-8.00(m,1H),7.94(d,J＝8.0Hz,1H),7.71-7.67(m,1H),7.40(d,J＝8.5Hz,2H),7.30(s,1H),6.93(d,J＝8.6Hz,2H),4.78(s,2H). 19 F NMR(376MHz,DMSO)δ-90.88. 13 CNMR (101MHz, DMSO) delta 158.97,157.14,155.08,147.89,147.37,144.28,139.65,139.20,137.61,136.63,129.58,127.83,127.80,127.40,127.02,123.02,121.49,118.78,115.27,114.03,110.18,107.42,55.09 HRMS (ESI-TOF) molecular formula C 23 H 14 BrClFN 7 O 2 :[M-H] - Calculated relative molecular mass: 553.0070, found 553.0068.
Example 13: preparation of 3-bromo-1- (3-chloropyridin-2-yl) -N- (1, 1-dioxide-4H-7-benzo [ e ] [1,2,4] thiadiazinyl) -1H-pyrazole-5-carboxamide 5-aminobenzo [ d ] [1,2,3] triazin-4 (3H) -one
Step 1
Figure BDA0003148260290000242
2-chloro-5-nitrobenzenesulfonamide (40 mmol), ammonium carbonate (80 mmol) and copper sulfate (12 mmol) were added to aqueous ammonia (100 mL) and heated in a high pressure flask at 120 ℃ for 4 hours. And (4) detecting the completion of the reaction by TLC, cooling the reaction solution to normal temperature, and pouring the reaction solution into water for precipitation. And (4) carrying out suction filtration, washing a filter cake with water, and drying to obtain a solid product 7.38g with the yield of more than 85%.
Step 2 Synthesis of 7-Nitro-4H-benzo [ e ] [1,2,4] thiadiazine 1, 1-dioxide
Figure BDA0003148260290000251
2-amino-5-nitrobenzenesulfonamide (30 mmol) was added to trimethyl orthoformate (100 mL) and stirred to give a suspension. The reaction was heated to 140 ℃ and the progress of the reaction was followed by TLC. After the reaction is finished, cooling to room temperature, and pouring into water for precipitation. And (4) carrying out suction filtration, washing a filter cake with water, and drying to obtain a solid product of 4.77g with the yield of more than 70%.
Step 3 Synthesis of 7-amino-4H-benzo [ e ] [1,2,4] thiadiazine 1, 1-dioxide
Figure BDA0003148260290000252
7-Nitro-4H-benzo [ e ] [1,2,4] thiadiazine 1, 1-dioxide (10 mmol), iron powder (50 mmol), ammonium chloride (30 mmol) were added to a 100mL eggplant-type bottle, and 20mL of ethanol and 8mL of water were added to dissolve them. Heating to 75 ℃, and carrying out reflux reaction for 0.5h. Filtering with diatomite, collecting filtrate, removing ethanol and water by rotary evaporation to obtain solid, separating and purifying by column chromatography (eluent: 10% methanol/dichloromethane), and evaporating solvent to obtain yellow solid product 1.48g with yield over 75%.
Step 4 Synthesis of 3-bromo-1- (3-chloropyridin-2-yl) -N- (1, 1-dioxido-4H-7-benzo [ e ] [1,2,4] thiadiazinyl) -1H-pyrazole-5-carboxamide 5-aminobenzo [ d ] [1,2,3] triazin-4 (3H) -one
Figure BDA0003148260290000253
A100 mL round-bottomed flask was charged with 7-amino-4H-benzo [ e ] [1,2,4] thiadiazine 1, 1-dioxide (7 mmol), 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid (14 mmol), N-methylimidazole (49 mmol), N, N, N ', N' -tetramethylchlorourea hexafluorophosphate (16.8 mmol), and dissolved in 40mL of acetonitrile. Heating to 60 ℃, refluxing for 6h, and detecting the completion of the reaction by TLC. The mixture was poured into water and a precipitate precipitated out. Filtering, washing precipitate with excessive water, and drying to obtain solid. The final white solid product (1.72 g) was obtained by column chromatography for separation and purification (eluent: 15% methanol/dichloromethane) and evaporation of the solvent to dryness, with a yield of over 51%.
The final test results were as follows: 1 H NMR(400MHz,DMSO)δ12.34(s,1H),10.87(s,1H),8.54(dd,J＝4.7,1.4Hz,1H),8.25(dd,J＝8.1,1.4Hz,1H),8.15(d,J＝2.3Hz,1H),7.96(s,1H),7.86(dd,J＝9.0,2.3Hz,1H),7.67(dd,J＝8.1,4.7Hz,1H),7.48(s,1H),7.34(d,J＝9.0Hz,1H). 13 c NMR (101MHz, DMSO). Delta.160.66, 155.90,148.27,146.69,140.02,136.85,136.52,133.71,132.79,125.71,125.42,123.42,119.91,118.69,115.01,114.38 HRMS (ESI-TOF) molecular formula C 16 H 10 BrClN 6 O 3 S:[M-H] - Calculated relative molecular mass: 478.9334, found 478.9328.
Example 14: preparation of 3-bromo-1- (3-chloropyridin-2-yl) -N- (3-methyl-1, 1-dioxide-4H-7-benzo [ e ] [1,2,4] thiadiazinyl) -1H-pyrazole-5-carboxamide 5-aminobenzo [ d ] [1,2,3] triazin-4 (3H) -one
Figure BDA0003148260290000261
A synthesis similar to that of example 13 was used, except that:
example 13 trimethyl orthoformate as solvent in step 2 triethyl orthoacetate was used.
The final test results were as follows: 1 H NMR(400MHz,DMSO)δ10.85(s,1H),8.56-8.48(m,1H),8.29-8.21(m,1H),8.10(d,J＝1.9Hz,1H),7.88-7.83(m,1H),7.70-7.65(m,1H),7.47(s,1H),7.30(d,J＝9.0Hz,1H),7.48(s,1H),2.87(s,3H). 13 c NMR (101MHz, DMSO). Delta.160.60, 158.01,155.89,148.21,140.19,137.79,136.82,135.13,132.82,125.63,125.48,124.15,121.87,119.18,116.82,114.43,19.25 HRMS (ESI-TOF) molecular formula C 17 H 12 BrClN 6 O 3 S:[M-H] - Calculated relative molecular mass: 492.9491, found 492.9489.
Example 15: preparation of 3-bromo-1- (3-chloro-2-pyridinyl) -N- (1-ethyl-4-oxo-1, 4-dihydro-6-quinazolinyl) -1H-pyrazole-5-carboxamide
Step 1
Figure BDA0003148260290000271
6-Nitro-4 (1H) -quinazolinone (20.00 mmol) was added to a 100mL eggplant-shaped flask, dissolved by adding 40mL acetonitrile, and bromoethane (40.00 mmol) and triethylamine (TEA, 60.00 mmol) were added to the eggplant-shaped flask in this order. Heating to 80 ℃, and refluxing for 5h. After the reaction, the reaction mixture was cooled to room temperature, and the solvent was evaporated under reduced pressure. To the residue was added water, extracted with dichloromethane three times, and the organic phases were combined. Drying with anhydrous sodium sulfate, filtering, and concentrating the filtrate to obtain solid product 3.72g with yield over 85%.
Step 2
Figure BDA0003148260290000272
1-Ethyl-6-amino-4 (1H) -quinazolinone (10 mmol), iron powder (50 mmol), ammonium chloride (30 mmol) were added to a 100mL eggplant-shaped bottle, 20mL ethanol and 8mL water were added to dissolve. Heating to 75 deg.C, reflux reacting for 0.5h, filtering with diatomite, and collecting filtrate. Ethanol and water were removed by rotary evaporation to obtain a solid, which was separated and purified by column chromatography (eluent: 10% methanol/dichloromethane), and the solvent was evaporated to dryness to obtain 1.42g of a yellow solid product with a yield of 75% or more.
Step 3 Synthesis of 3-bromo-1- (3-chloro-2-pyridinyl) -N- (1-ethyl-4-oxo-1, 4-dihydro-6-quinazolinyl) -1H-pyrazole-5-carboxamide
Figure BDA0003148260290000273
In a 100mL round bottom flask, 1-ethyl-6-amino-4 (1H) -quinazolinone (7 mmol), 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid (14 mmol), N-methylimidazole (49 mmol), N' -tetramethylchlorourea hexafluorophosphate (16.8 mmol) was added and dissolved in 40mL acetonitrile. Heating to 60 ℃, refluxing for 6h, and detecting the completion of the reaction by TLC. The mixture was poured into water, and the precipitate was precipitated and filtered. The precipitate was washed with excess water and dried to give a solid. The crude product was purified by column chromatography (eluent: 16% methanol/dichloromethane), and the solvent was evaporated to dryness to give 1.69g of the final white solid product with a yield of over 51%.
The final test results were as follows: 1 H NMR(400MHz,DMSO)δ10.88(s,1H),8.58-8.54(m,1H),8.49(d,J＝2.4Hz,1H),8.36(s,1H),8.29-8.23(m,1H),8.05-8.01(m,1H),7.72-7.68(m,1H),7.67(d,J＝3.3Hz,1H),7.52(s,1H),4.00(q,J＝7.1Hz,2H),1.28(t,J＝7.1Hz,3H). 13 c NMR (101MHz, DMSO). Delta.163.28, 161.62,160.57,155.85,148.27,140.18,139.39,137.87,136.85,132.75,128.77,125.71,125.42,123.91,117.87,114.46,114.42,45.38,12.39 HRMS (ESI-TOF) molecular formula C 19 H 13 BrClN 6 O 2 :[M-H] - Calculated relative molecular mass: 470.9977, found 470.9980.
Example 16: preparation of 3-difluoromethyl-1- (3-chloro-2-pyridinyl) -N- (4-oxo-1, 4-dihydro-6-quinazolinyl) -1H-pyrazole-5-carboxamide
Figure BDA0003148260290000281
A synthesis similar to that of example 15 was used, except that:
example 15 direct nitro reduction of starting material 6-nitro-4 (1H) -quinazolinone in step 1; in the step 3, 3-difluoromethyl-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid is used as the raw material 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid.
The final test results were as follows: 1 H NMR(400MHz,DMSO)δ12.24(s,1H),10.86(s,1H),8.58-8.54(m,1H),8.46(d,J＝2.2Hz,1H),8.28-8.24(m,1H),8.04(s,1H),8.03-7.98(m,1H),7.71-7.67(m,1H),7.66(d,J＝3.6Hz,1H),7.52(s,1H),6.45(s,1H). 19 F NMR(376MHz,DMSO)δ-115.52. 13 c NMR (101MHz, DMSO). Delta.163.22, 161.60,155.91,150.35,148.27,140.14,137.25,136.91,135.56,132.79,125.70,125.48,122.94,122.91,116.89,116.17,114.45,113.82 HRMS (ESI-TOF) molecular formula C 18 H 11 ClF 2 N 6 O 2 :[M-H] - Calculated relative molecular mass: 416.0606, found 416.0603.
Example 17: preparation of 3-bromo-1- (3-chloro-2-pyridinyl) -N- (1-benzyl-4-oxo-1, 4-dihydro-6-quinazolinyl) -1H-pyrazole-5-carboxamide
Figure BDA0003148260290000291
A synthesis similar to that of example 15 was used, except that:
example 15 ethyl bromide, starting material in step 1, benzyl bromide was used.
The final test results were as follows: 1 H NMR(400MHz,DMSO)δ10.85(s,1H),8.56-8.52(m,1H),8.42(d,J＝2.2Hz,1H),8.26-8.21(m,1H),8.02(s,1H),8.01-7.97(m,1H),7.40-7.35(m,5H)7.70-7.65(m,1H),7.62(d,J＝3.6Hz,1H),7.50(s,1H),5.23(s,2H). 13 c NMR (101MHz, DMSO). Delta.163.22, 161.60,155.91,150.35,148.27,140.14,137.25,136.91,135.56,132.79,125.70,125.48,122.94,122.91,116.89,116.17,114.45 HRMS (ESI-TOF) molecular formula C 24 H 16 BrClN 6 O 2 :[M-H] - Calculated relative molecular mass: 533.0134, found 533.0141.
Example 18: preparation of 3-bromo-1- (3-chloro-2-pyridinyl) -N- (2-isopropyl-1, 3-tetraoxide-2H-benzo [ d ] [1,3,2] dithiazolyl) -1H-pyrazole-5-carboxamide
Figure BDA0003148260290000292
A synthesis similar to that of example 1 was used, except that:
example 1 the starting material bromoethane in step 1, 2-bromopropane was used, starting material 5-nitrophthalimide, and 6-nitro-1, 1-dioxide-benzo [ d ] isothiazole was used.
The final test results were as follows: 1 H NMR(400MHz,DMSO)δ10.89(s,1H),8.56-8.54(m,1H),8.27-8.25(m,1H),8.09(d,J＝1.3Hz,1H),7.98-7.96(m,1H),7.81(d,J＝8.2Hz,1H),7.70-7.67(m,1H),7.51(s,1H),4.41-4.33(m,1H),1.38(d,J＝6.9Hz,6H). 13 c NMR (101MHz, DMSO). Delta.163.86, 161.60,155.90,148.22,140.75,140.13,138.74,136.88,133.35,132.81,130.37,125.70,125.41,124.12,120.89,114.46,53.92,20.41 HRMS (ESI-TOF) molecular formula C 19 H 15 BrClN 5 O 4 S:[M-H] - Calculated relative molecular mass: 522.9722, found 522.9720.
Example 19: preparation of 3-difluoromethyl-1-methyl-N- (2- (4-methoxybenzyl) -1-oxo-5-isoindolyl) -1H-pyrazole-5-carboxamide
Figure BDA0003148260290000301
A synthesis similar to that of example 1 was used, except that:
example 1 starting material bromoethane in step 1, 4-methoxybenzyl bromide, starting material 5-nitrophthalimide, 5-nitro-1-isoindolone; in the step 3, 3-difluoromethyl-1-methyl-1H-pyrazole-5-carboxylic acid is adopted as the raw material 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid.
The final test results were as follows: 1 H NMR(400MHz,DMSO)δ11.02(s,1H),8.58-8.52(m,1H),8.29-8.22(m,1H),8.12(d,J＝0.9Hz,1H),7.52(s,1H),7.19(d,J＝8.0Hz,2H),7.11(d,J＝7.9Hz,2H),6,52(s,1H),4.72(s,2H),4.22(s,2H)3.96(s,3H).3.81(s,3H). 19 F NMR(376MHz,DMSO)δ-112.38. 13 c NMR (101MHz, DMSO). Delta.161.69, 159.52,155.87,148.27,141.49,140.15,137.97,136.88,136.75,132.99,132.76,130.04,128.95,128.54,125.72,122.56,114.48,114.09,55.67,50.45,40.98,21.17.HRMS (ESI-TOF) molecular formula C 22 H 20 F 2 N 4 O 3 :[M-H] - Calculated relative molecular mass: 426.1509, found 426.1511.
Example 20: preparation of 3-bromo-1- (3-chloro-2-pyridinyl) -N- (2-ethyl-1, 1-dioxo-3-oxo-3, 4-dihydro-2H-benzo [ e ] [1,2,4] thiadiazinyl) -1H-pyrazole-5-carboxamide
Step 1 Synthesis of 2-ethyl-7-nitro-2H-benzo [ e ] [1,2,4] thiadiazine-3 (4H) -1, 1-dioxide
Figure BDA0003148260290000302
7-Nitro-2H-benzo [ e ] [1,2,4] thiadiazine-3 (4H) -1, 1-dioxide (20.00 mmol) was added to a 100mL eggplant type bottle, 50mL of N, N-dimethylformamide was added thereto to dissolve, and bromoethane (20.00 mmol) and triethylamine (TEA, 60.00 mmol) were added to the eggplant type bottle in this order. Heating to 90 ℃, and refluxing for 5h. The mixture was then poured into ice water and a precipitate precipitated out. The precipitate was filtered, washed with excess water and dried at 70-75 ℃. The obtained crude solid product was purified by recrystallization from ethanol to obtain 4,36g as a white solid with a yield of 80.5%.
Step 2 Synthesis of 2-ethyl-7-amino-2H-benzo [ e ] [1,2,4] thiadiazine-3 (4H) -1, 1-dioxide
Figure BDA0003148260290000311
2-Ethyl-7-nitro-2H-benzo [ e ] [1,2,4] thiadiazine-3 (4H) -1, 1-dioxide (10 mmol), iron powder (50 mmol), ammonium chloride (30 mmol) were added to a 100mL eggplant-shaped bottle, 30mL of ethanol and 12mL of water were added to dissolve. Heating to 75 ℃, and carrying out reflux reaction for 0.5h. Filtering with diatomite to obtain filtrate. And (4) removing ethanol and water by rotary evaporation to obtain a solid. Separation and purification by column chromatography (eluent: 10% methanol/dichloromethane) and evaporation of the solvent gave 1.81g of a yellow solid product in 75% or more yield.
And step 3: synthesis of 3-bromo-1- (3-chloro-2-pyridyl) -N- (2-ethyl-1, 1-dioxo-3-oxo-3, 4-dihydro-2H-benzo [ e ] [1,2,4] thiadiazinyl) -1H-pyrazole-5-carboxamide
Figure BDA0003148260290000312
A100 mL round-bottomed flask was charged with 2-ethyl-7-amino-2H-benzo [ e ] [1,2,4] thiadiazine-3 (4H) -1, 1-dioxide (5 mmol), 3-bromo-1- (2-chloropyridyl) -1H-pyrazole-5-carboxylic acid (10 mmol), N-methylimidazole (35 mmol), N, N, N ', N' -tetramethylchlorourea hexafluorophosphate (12 mmol), and dissolved in 40mL of acetonitrile. Heating to 60 ℃, refluxing for 6h, and detecting the completion of the reaction by TLC. The mixture was poured into water and a precipitate precipitated out. The precipitate was filtered and washed with excess water to give a solid. The crude product was purified by column chromatography (eluent: 15% methanol/dichloromethane), and the solvent was evaporated to dryness to give 1.34g of the final white solid product with a yield of over 51%.
The final test results were as follows: 1 H NMR(400MHz,DMSO)δ12.02(s,1H),10.85(s,1H),8.61-8.55(m,1H),8.48(d,J＝2.4Hz,1H),8.35(s,1H),8.27-8.21(m,1H),8.05-7.98(m,1H),7.69-7.62(m,1H),7.51(s,1H),4.00(q,J＝7.1Hz,2H),1.28(t,J＝7.1Hz,3H). 13 C NMR(101MHz,DMSO)δ161.60,155.98,149.11,148.32,140.18,136.85,136.53,132.79,131.57,126.32,125.70,125.46,123.77,121.16,114.71,114.42,38.45,13.62.HRMS (ESI-TOF) molecular formula is C 18 H 14 BrClN 6 O 4 S:[M-H] - Calculated relative molecular mass: 522.9596, found 522.9591.
Example 21: preparation of 3-bromo-1- (3-chloro-2-pyridinyl) -N- (2-fluoroethyl-2, 4-dioxo-1, 2,3, 4-tetrahydroquinazolinyl) -1H-pyrazole-5-carboxamide
Figure BDA0003148260290000321
A synthesis similar to that of example 20 was used, except that:
example 20 starting material 7-nitro-2H-benzo [ e ] [1,2,4] thiadiazine-3 (4H) -1, 1-dioxide in step 1, using 6-nitroquinazoline-2, 4 (1h, 3h) -dione; 1-bromo-2-fluoroethane is used as the raw material bromoethane.
The final test results were as follows: 1 H NMR(400MHz,DMSO)δ11.96(s,1H),10.79(s,1H),8.62-8.53(m,1H),8.50(d,J＝2.4Hz,1H),8.37(s,1H),8.26-8.19(m,1H),8.07-7.99(m,1H),7.71-7.64(m,1H),7.53(s,1H),4.52-4.50(m,2H),3.35(t,J＝7.1Hz,2H). 19 F NMR(376MHz,DMSO)δ-90.82. 13 c NMR (101MHz, DMSO). Delta.162.72, 161.60,155.95,150.57,148.31,140.19,138.44,137.02,136.88,132.81,127.34,125.71,125.42,124.05,117.65,114.47,110.24,35.25,14.57 HRMS (ESI-TOF) molecular formula C 19 H 13 BrClFN 6 O 3 :[M-H] - Calculated relative molecular mass: 505.9911, found 505.9910.
Example 22: preparation of 3-bromo-1- (3-chloro-2-pyridinyl) -N- (1, 4-dioxo-1, 2,3, 4-tetrahydrophthalazinyl) -1H-pyrazole-5-carboxamide
Step 1: synthesis of 7-amino-2, 3-dihydrophthalazine-1, 4-dione
Figure BDA0003148260290000322
2-Ethyl-7-nitro-2, 3-dihydrophthalazine-1, 4-dione (10 mmol), iron powder (50 mmol), ammonium chloride (30 mmol) were added to a 100mL eggplant-shaped bottle, and 30mL ethanol and 12mL water were added to dissolve. Heated to 75 ℃ and refluxed for 0.5h. Filtering with diatomaceous earth, collecting filtrate, and removing ethanol and water by rotary evaporation to obtain solid. Separation and purification by column chromatography (eluent: 10% methanol/dichloromethane) and evaporation of the solvent gave 1.33g of a yellow solid product in 75% or more yield.
Step 2: synthesis of 3-bromo-1- (3-chloro-2-pyridinyl) -N- (1, 4-dioxo-1, 2,3, 4-tetrahydrophthalazinyl) -1H-pyrazole-5-carboxamide
Figure BDA0003148260290000331
In a 100mL round-bottomed flask was added 2-ethyl-7-amino-2, 3-dihydrophthalazine-1, 4-dione (5 mmol), 3-bromo-1- (2-chloropyridyl) -1H-pyrazole-5-carboxylic acid (10 mmol), N-methylimidazole (35 mmol), N, N, N ', N' -tetramethylchlorourea hexafluorophosphate (12 mmol), and dissolved in 40mL of acetonitrile. Heating to 60 ℃, refluxing for 6h, and detecting the completion of the reaction by TLC. The mixture was poured into water and a precipitate precipitated out. The precipitate was filtered and washed with excess water to give a solid. The final white solid product (1.17 g) was obtained by column chromatography for separation and purification (eluent: 15% methanol/dichloromethane) and evaporation of the solvent to dryness, with a yield of over 51%.
The final test results were as follows: 1 H NMR(400MHz,DMSO)δ11.55-11.46(m,2H),11.03(s,1H),8.56-8.54(m,1H),8.39(s,1H),8.27-8.25(m,1H),8.09-8.03(m,1H),7.70-7.67(m,2H),7.56(s,1H). 13 c NMR (101MHz, DMSO). Delta.160.82, 156.91,155.95,154.02,148.31,141.80,140.19,138.63,136.90,132.82,129.93,127.25,125.96,125.77,125.46,118.01,114.42 HRMS (ESI-TOF) molecular formula C 17 H 10 BrClN 6 O 3 :[M-H] - Calculated relative molecular mass: 459.9692, found 459.9694.
The other compounds in Table 1 were prepared in a similar manner to examples 1-22, using different starting materials, pyrazole compounds.
In order to further prove the biological activity of the pyrazole amide compound containing the aromatic heterocyclic structure, the inventor designs the following test method.
The same test method is adopted for diamondback moth and armyworm, and the leaf soaking method is adopted. Firstly, dissolving the surfactant with the concentration of less than 10% in tap water, and performing microwave ultrasonic treatment to promote the uniform dissolution of the surfactant. Dimethyl sulfoxide (DMSO) with concentration not higher than 5% is used as cosolvent, tap water with dissolved surfactant is added to prepare different preparations with different concentrations. Soaking corn leaf seedlings in different agents with different concentrations for treatment, airing, placing the corn leaf seedlings in culture dishes, then respectively inoculating 10 larvae of diamondback moths or armyworms with the age of 2-3 in each culture dish, setting three groups of parallel experiments, adding blank control and chlorantraniliprole as positive control, observing every 24 hours, supplementing fresh leaves to the corn leaf seedlings when the leaves are eaten by the insects, recording death and survival numbers after 72 hours, and calculating the death rate.
Mortality (%) = (number of control live insects-number of treated live insects)/number of control live insects × 100%.
The structures of the pyrazole amide compounds containing aromatic heterocyclic structures and the measurement results of the biological activities of the pyrazole amide compounds on armyworm larvae and diamondback moth larvae are shown in the table 1.
TABLE 1
Figure BDA0003148260290000341
Figure BDA0003148260290000351
Figure BDA0003148260290000361
Figure BDA0003148260290000371
Figure BDA0003148260290000381
Figure BDA0003148260290000391
Figure BDA0003148260290000401
Figure BDA0003148260290000411
Figure BDA0003148260290000421
Figure BDA0003148260290000431
Figure BDA0003148260290000441
Figure BDA0003148260290000451
Figure BDA0003148260290000461
Figure BDA0003148260290000471
Figure BDA0003148260290000481
Figure BDA0003148260290000491
All documents referred to herein are incorporated by reference into this application as if each were individually incorporated by reference. Furthermore, it should be understood that various changes and modifications of the present invention can be made by those skilled in the art after reading the above teachings of the present invention, and these equivalents also fall within the scope of the present invention as defined by the appended claims.

Claims (10)

1. A pyrazole amide compound containing an aromatic heterocyclic structure, an optical isomer, a cis-trans isomer or an agriculturally and pharmaceutically acceptable salt thereof is characterized in that the compound has a structure shown in a formula I,
Figure FDA0003148260280000011
wherein,
R 1 selected from the group consisting of substituted or unsubstituted: c 1-6 Alkyl radical, C 3-6 Cycloalkyl radical, C 2-6 Alkenyl radical, C 2-6 Alkynyl, C 1-8 Alkoxy, hydrogen, phenyl, naphthalenylcyclyl, 5-6 membered heteroaryl, amino, hydroxyl, amido, acyloxy, carboxymethyl, nitro, cyano, sulfonic acid, halogen, formyl, acyl, carboxyl; by substituted is meant substituted with one or more (e.g., 2,3,4, or 5) substituents selected from the group consisting of: halogen, hydroxy, C 1-6 Alkoxy radical, C 1-6 Alkyl, amino, nitro, carboxyl, carboxymethyl, cyano, C 1-6 Haloalkyl, amido, acyloxy, C 3-6 Cycloalkyl radical, C 3-6 Halogenocycloalkyl, C 2-6 Alkenyl radical, C 2-6 Haloalkenyl, C 2-6 Alkynyl, C 2-6 Halogenated alkynyl, C 5-7 A cycloalkenyl group;
R 2 selected from the group consisting of substituted or unsubstituted: c 1-6 Alkyl radical, C 3-6 Cycloalkyl, C 2-6 Alkenyl radical, C 2-6 Alkynyl radical、C 1-6 Alkoxy, phenyl, hydrogen, amino, hydroxyl, amide, acyloxy, carboxymethyl, nitro, cyano, sulfonic, halogen, formyl, acyl, carboxyl; the substitution refers to substitution by one or more halogens;
a is selected from substituted or unsubstituted phenyl, substituted or unsubstituted naphthalene cyclyl, substituted or unsubstituted 4-8 membered heteroaryl, substituted or unsubstituted C 8-14 A heteroaromatic bicyclic or tricyclic ring system; by substituted is meant substituted with one or more (e.g., 2,3,4, or 5) substituents selected from the group consisting of: halogen, hydroxy, C 1-6 Alkoxy radical, C 1-6 Alkyl, amino, nitro, carboxyl, carboxymethyl, cyano, C 1-6 Haloalkyl, amido, acyloxy, C 3-6 Cycloalkyl radical, C 3-6 Halogenocycloalkyl, C 2-6 Alkenyl radical, C 2-6 Halogenated alkenyl group, C 2-6 Alkynyl, C 2-6 Halogenated alkynyl, C 5-7 Cycloalkenyl, phenyl, naphthyl;
b is an unsaturated or saturated 5-6 membered nitrogen containing heterocyclic group, wherein said heterocyclic group contains at least one N heteroatom and 0-2 heteroatoms selected from N, O or S;
n is selected from 0 or 1;
y is selected from the group consisting of: hydrogen, C 1-6 Alkoxy radical, C 1-8 Alkyl radical, C 1-6 Haloalkyl, C 3-6 Cycloalkyl radical, C 3-6 Halocycloalkyl radical, C 2-6 Alkenyl radical, C 2-6 Halogenated alkenyl group, C 2-6 Alkynyl, C 2-6 Halogenated alkynyl, C 5-7 Cycloalkenyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthalenylcyclyl, substituted or unsubstituted 4-8 membered heteroaryl, substituted or unsubstituted C 8-14 A heteroaromatic bicyclic or tricyclic ring system, or a 3-7 membered heterocyclic group; by substituted is meant substituted with one or more (e.g., 2,3,4, or 5) substituents selected from the group consisting of: c 1-6 Alkyl radical, C 2-6 Alkenyl, halogen, C 1-6 Haloalkyl, cyano, amino, nitro, carboxyl, carboxymethyl, amido, acyloxy, C 3-6 Cycloalkyl, C 3-6 Halogenocycloalkyl, C 2-6 Haloalkenyl, C 2-6 Alkynyl, C 2-6 Halogenated alkynyl group,C 5-7 Cycloalkenyl, phenyl, naphthyl.
2. The compound of claim 1, wherein R is 1 Selected from the group consisting of substituted or unsubstituted: c 1-6 Alkyl radical, C 2-6 Alkenyl radical, C 1-6 Alkoxy, phenyl, 5-6 membered heteroaryl, hydrogen, amino, amido, halo, formyl, acyl, carboxy; said substitution means substitution by one or more (e.g. 2,3,4 or 5) substituents selected from the group consisting of: halogen, hydroxy, C 1-6 Alkoxy radical, C 1-6 Alkyl, amino, nitro, carboxyl, carboxymethyl, cyano, C 1-6 Haloalkyl, amide, acyloxy;
R 2 selected from the group consisting of substituted or unsubstituted: c 1-5 Alkyl radical, C 3-5 Cycloalkyl, C 2-5 Alkenyl radical, C 2-6 Alkynyl, C 1-6 Alkoxy, halogen; said substitution refers to substitution by one or more halogens;
a is selected from substituted or unsubstituted phenyl, substituted or unsubstituted 4-8 membered heteroaryl; the substitution means substitution by one or more substituents selected from the group consisting of: halogen, hydroxy, C 1-6 Alkoxy radical, C 1-6 Alkyl, amino, nitro, carboxyl, carboxymethyl, cyano, C 1-6 Haloalkyl, amido, acyloxy, C 3-6 Cycloalkyl radical, C 3-6 Halogenocycloalkyl, C 2-6 Alkenyl radical, C 2-6 Haloalkenyl, C 2-6 Alkynyl, C 2-6 Halogenated alkynyl, C 5-7 Cycloalkenyl, phenyl, naphthyl;
b is an unsaturated 5-6 membered nitrogen containing heterocyclyl wherein said heterocyclyl contains at least one N heteroatom and 0-2 heteroatoms selected from N, O or S;
y is selected from the group consisting of: hydrogen, C 1-6 Alkoxy radical, C 1-6 Alkyl radical, C 1-6 Haloalkyl, C 3-6 Cycloalkyl, C 2-6 Alkenyl radical, C 2-6 Alkynyl, substituted or unsubstituted phenyl, substituted or unsubstituted 4-8 membered heteroaryl; the substitution means substitution with one or more substituents selected from the group consisting of: c 1-6 Alkyl radical、C 2-6 Alkenyl, halogen, C 1-6 Haloalkyl, cyano, amino, nitro, carboxyl, carboxymethyl, amido, acyloxy, C 3-6 Cycloalkyl radical, C 3-6 Halogenocycloalkyl, C 2-6 Haloalkenyl, C 2-6 Alkynyl, C 2-6 Halogenated alkynyl, C 5-7 Cycloalkenyl, phenyl, naphthyl.
3. The compound of claim 2, wherein R is 1 Selected from the group consisting of substituted or unsubstituted: c 1-6 Alkyl, phenyl, 5-6 membered heteroaryl, hydrogen, amino, amido, halogen; the substitution means substitution with one or more substituents selected from the group consisting of: halogen, hydroxy, C 1-6 Alkoxy radical, C 1-6 Alkyl, amino, nitro, carboxyl;
R 2 selected from the group consisting of substituted or unsubstituted: c 1-5 Alkyl radical, C 1-6 Alkoxy radical, C 2-5 Alkenyl, halogen; said substitution refers to substitution by one or more halogens;
a is selected from substituted or unsubstituted phenyl; the substitution refers to substitution by one or more substituents selected from the group consisting of: halogen, hydroxy, C 1-6 Alkoxy radical, C 1-6 Alkyl, amino, nitro, carboxyl, cyano, C 1-6 Haloalkyl, amide, acyloxy;
b is selected from the following group:
Figure FDA0003148260280000031
y is selected from the group consisting of: hydrogen, C 1-6 Alkoxy radical, C 1-6 Alkyl radical, C 1-6 Haloalkyl, C 2-6 Alkenyl, substituted or unsubstituted phenyl, substituted or unsubstituted 4-8 membered heteroaryl; the substitution means substitution with one or more substituents selected from the group consisting of: c 1-6 Alkyl radical, C 2-6 Alkenyl, halogen, C 1-6 Haloalkyl, cyano, amino, nitro, carboxyl, carboxymethyl, amido, acyloxy.
4. A compound of claim 3 wherein R is 1 Selected from the group consisting of substituted or unsubstituted: c 1-6 Alkyl, phenyl, 5-6 membered heteroaryl; the substitution means substitution with one or more substituents selected from the group consisting of: halogen, hydroxy, C 1-6 Alkoxy radical, C 1-6 Alkyl, amino, nitro, carboxyl;
R 2 selected from the group consisting of substituted or unsubstituted: c 1-5 Alkyl, halogen; the substitution refers to substitution by one or more halogens;
y is selected from the group consisting of: hydrogen, C 1-6 Alkyl radical, C 1-6 Haloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted 4-8 membered heteroaryl; the substitution means substitution with one or more substituents selected from the group consisting of: c 1-6 Alkyl radical, C 2-6 Alkenyl, halogen, C 1-6 Haloalkyl, cyano, amino, nitro, carboxyl, carboxymethyl, amido, acyloxy.
5. A compound of claim 4, wherein R is 1 Selected from the group consisting of substituted or unsubstituted: c 1-5 Alkyl, phenyl, pyridyl; the substitution refers to substitution by one or more halogens;
R 2 selected from halogen and C 1-5 A haloalkyl group.
6. The compound of claim 1, wherein R is 1 Selected from the group consisting of substituted or unsubstituted: phenyl, 5-6 membered heteroaryl, hydrogen, amino, nitro, cyano, sulfonic acid, halogen; the substitution refers to substitution by one or more halogens.
7. The compound of claim 1, wherein B is selected from the group consisting of:
Figure FDA0003148260280000041
8. a pesticidal composition, comprising:
1) 0.001 to 99.99% by weight of a compound of claim 1, an optical isomer, a cis-trans isomer, or an agriculturally pharmaceutically acceptable salt thereof, or a combination thereof; and
2) An agriculturally pharmaceutically acceptable carrier and/or excipient.
9. Use of a compound of claim 1, an optical isomer, a cis-trans isomer, or an agriculturally pharmaceutically acceptable salt thereof, for controlling lepidopteran pests; or for the preparation of insecticides and/or acaricides for controlling lepidopteran pests.
10. A method of combating and/or killing insects, which comprises applying a compound according to claims 1 to 7 or an agriculturally acceptable salt thereof or a pesticidal composition according to claim 8 to a plant suffering from a condition susceptible to insect infestation, the soil surrounding the same or to the environment.
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