CN113896712A - Diamide compound containing cyclic amino acid - Google Patents

Diamide compound containing cyclic amino acid Download PDF

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CN113896712A
CN113896712A CN202111341701.8A CN202111341701A CN113896712A CN 113896712 A CN113896712 A CN 113896712A CN 202111341701 A CN202111341701 A CN 202111341701A CN 113896712 A CN113896712 A CN 113896712A
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radical
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aryl
halo
halogen
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CN113896712B (en
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李忠
陈睿嘉
王俊杰
冯婷婷
董乐凤
王港澳
韩醴
徐晓勇
邵旭升
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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
    • C07D401/02—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 two hetero rings
    • C07D401/04—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 two hetero rings directly linked by a ring-member-to-ring-member bond
    • 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
    • A01N53/00—Biocides, pest repellants or attractants, or plant growth regulators containing cyclopropane carboxylic acids or derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D231/16—Halogen atoms or nitro radicals
    • 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
    • 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
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Agronomy & Crop Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Dentistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
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  • Environmental Sciences (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

The invention discloses a diamide compound containing cyclic amino acid and a preparation method and application thereof, wherein the compound has a chemical structure shown in a formula I. The compound of the invention is used as an insecticide, has good control effect on diamondback moth, armyworm and the like, and is expected to become a novel insecticideAnd (3) preparing.

Description

Diamide compound containing cyclic amino acid
Technical Field
The present invention relates to cyclic amino acid-containing diamide compounds, to a process for preparing them, to their use as active agents of insecticides, and to methods and uses of these compounds and their compositions for controlling pests in agricultural, forestry, horticultural environments.
Background
Insect pests cause huge losses to agricultural production. Chemical pesticides are one of the effective means for the comprehensive management of pests. The pesticide with high efficiency, environmental protection, unique action mechanism and no cross resistance with the prior pesticide is always the demand and target of plant protection workers.
Patent US2005075372a1 discloses a diamide compound having insecticidal activity and application thereof. Among them, compound S1 has been developed as a commercial insecticide, commonly known as chlorantraniliprole.
Figure BDA0003352346640000011
Patent CN102924433A discloses a diamide compound containing glycine substructure, which has a certain insecticidal activity. The compound containing cyclic amino acid has wide biological activity, such as anticancer, antiphlogistic, bactericidal, etc. Cyclic amino acid substructures have emerged in an increasing number of pharmaceutical molecules. No compounds having excellent insecticidal activity have been reported in the art.
Disclosure of Invention
The invention aims to provide a diamide compound containing cyclic amino acid with a novel structure, which is used for controlling plant pests.
In a first aspect of the invention, a compound having a structure shown in a general formula (I), an optical isomer, a cis-trans isomer or an agriculturally and pharmaceutically acceptable salt thereof is provided,
Figure BDA0003352346640000021
in the formula (I), the compound is shown in the specification,
n is 1,2, 3 or 4;
x is N or CR11；
m is 1,2, 3,4,5, 6, 7 or 8;
R1each independently selected from the group consisting of: hydrogen, halogen, cyano, nitro, C2–C6Ester group, C2–C6A sulfonate group, oxo (C ═ O), or a substituted or unsubstituted group selected from the group consisting of: c1–C6Alkyl radical, C2–C6Alkenyl radical, C2–C6Alkynyl, C3–C6Cycloalkyl, 4-8 membered heterocyclyl, C6–C10Aryl, 5-8 membered heteroaryl, -CONHR12；
R2Is hydrogen or a substituted or unsubstituted group selected from the group consisting of: c1–C6Alkyl radical, C2–C6Alkenyl radical, C2–C6Alkynyl, C3–C6Cycloalkyl, 4-8 membered heterocyclyl, C6–C10Aryl, 5-8 membered heteroaryl, -COR13、–CONHR13、–NHCOR13；
R3、R4Each independently hydrogen or a substituted or unsubstituted group selected from: c1–C6Alkyl radical, C2–C6Alkenyl radical, C2–C6Alkynyl, C3–C6Cycloalkyl, 4-8 membered heterocyclyl, C6–C10Aryl (I-146), 5-8 membered heteroaryl; wherein said substitution is by one or more groups selected from the group consisting of: halogen, cyano, nitro, C2–C6Ester group, C2–C6Sulfonate group, C1–C4Alkyl, 4-8 membered heterocyclic group, C6–C10Aryl, 5-8 membered heteroaryl, halo C1–C4Alkyl, halo C2–C4Alkenyl, halo C2–C4Alkynyl, halo C3–C5Cycloalkyl, halo C6–C10Aryl, halogenated 5-8 membered heteroaryl, C1–C4An alkoxy group;
R5、R6、R7、R8、R9、R10each independently of the others is hydrogen, halogen, cyano, nitro, C2–C6Ester group, C2–C6A sulfonate group or a substituted or unsubstituted group selected from the group consisting of: c1–C6Alkyl radical, C2–C6Alkenyl radical, C2–C6Alkynyl, C3–C6Cycloalkyl, 4-8 membered heterocyclyl, C6–C10Aryl, 5-8 membered heteroaryl, C1–C6Alkoxy radical, C2–C6Alkenyloxy radical, C2–C6Alkynyloxy, C3–C6Cycloalkyl oxy, C6–C10Aryloxy, 5-8 membered heteroaryloxy, C1–C6Alkylthio radical, C2–C6Alkenylthio radical, C2–C6Alkynylthio, C3–C6Cycloalkylthio radical, C6–C10Arylthio, 5-to 8-membered heteroarylthio, C1–C6Alkylamino radical, C2–C6Enamine group, C2–C6Alkynylamino, C3–C6Cycloalkylamino group, C6–C10Arylamine group, 5-8 membered heteroaromatic amine group;
R11is hydrogen, halogen, cyano, nitro, C2–C6Ester group, C2–C6A sulfonate group,C1–C4Alkyl, 4-8 membered heterocyclic group, C6–C10Aryl, 5-8 membered heteroaryl;
R12is substituted or unsubstituted C1–C4Alkyl radical, C2–C4Alkenyl radical, C6–C10Aryl, 5-8 membered heteroaryl;
R13is substituted or unsubstituted C1–C4Alkyl radical, C2–C4Alkenyl radical, C3–C6Cycloalkyl, 4-8 membered heterocyclyl, C6–C10Aryl, 5-8 membered heteroaryl;
unless otherwise specified, the substitution refers to substitution by one or more groups selected from the group consisting of: halogen, cyano, nitro, C2–C6Ester group, C2–C6Sulfonate group, C1–C4Alkyl radical, C2–C4Alkenyl radical, C2–C4Alkynyl, C3–C5Cycloalkyl radical, C6–C10Aryl, 5-8 membered heteroaryl, halo C1–C3Alkyl, halo C2–C4Alkenyl, halo C2–C4Alkynyl, halo C3–C5Cycloalkyl, halo C6–C10Aryl, halogenated 5-8 membered heteroaryl, C1–C4Alkoxy radical, C2–C4Alkenyloxy radical, C2–C4Alkynyloxy, C3–C5Cycloalkyl oxy, C6–C10Aryloxy, 5-8 membered heteroaryloxy, C1–C4Alkylthio radical, C2–C4Alkenylthio radical, C2–C4Alkynylthio, C3–C5Cycloalkylthio radical, C6–C10Arylthio, 5-to 8-membered heteroarylthio, C1–C4Alkylamino radical, C2–C4Enamine group, C2–C4Alkynylamino, C3–C5Cycloalkylamino group, C6–C10Arylamine group and 5-8 membered heteroaromatic amine group.
In another preferred embodimentIn the examples, R is as defined11Selected from the group consisting of: hydrogen, halogen, cyano, C1–C4An alkyl group.
In another preferred embodiment, R is5And R6Each independently selected from the group consisting of: hydrogen, halogen, cyano, nitro, C2–C6Ester group, C2–C6A sulfonate group, or a substituted or unsubstituted group selected from: c1–C6Alkyl radical, C2–C6Alkenyl radical, C2–C6Alkynyl, C3–C6Cycloalkyl, 4-8 membered heterocyclyl, C6–C10Aryl, 5-8 membered heteroaryl; wherein said substitution is by one or more groups selected from the group consisting of: halogen, cyano, nitro, C2–C6Ester group, C2–C6Sulfonate group, C1–C4Alkyl radical, C2–C4Alkenyl radical, C2–C4Alkynyl, C3–C5Cycloalkyl radical, C6–C10Aryl, 5-8 membered heteroaryl.
In another preferred embodiment, the compound has a structure represented by general formula (II):
Figure BDA0003352346640000031
wherein, m, X, R1、R2、R3、R4、R5、R6、R7、R8、R9、R10As defined in the first aspect of the invention.
In another preferred embodiment, the compound has a structure represented by general formula (III):
Figure BDA0003352346640000041
wherein, X, R1、R1’、R2、R3、R4、R5、R6、R7、R8、R9、R10As defined in the first aspect of the invention.
In another preferred embodiment, the compound has a structure represented by general formula (III):
Figure BDA0003352346640000042
in the formula (I), the compound is shown in the specification,
x is N or CR11(ii) a Wherein R is11Is hydrogen, halogen, cyano, nitro, C1-C4Alkyl radical, C6-C10A phenyl group;
R1、R1'each independently selected from the group consisting of: hydrogen, halogen, cyano, nitro, C2–C6Ester group, C2–C6A sulfonate group and a substituted or unsubstituted of: c1–C6Alkyl radical, C2–C6Alkenyl radical, C2–C6Alkynyl, C3–C6Cycloalkyl, 4-8 membered heterocyclyl, C6–C10Aryl, 5-8 membered heteroaryl, -CONHR12；
R5Is hydrogen, halogen, cyano, nitro, C2–C6Ester group, C2–C6A sulfonate group or a substituted or unsubstituted group selected from the group consisting of: c1–C4Alkyl radical, C2–C4Alkenyl radical, C6–C10An aryl group; wherein said substitution is by one or more groups selected from the group consisting of: halogen, cyano, nitro, C2–C6Ester group, C1–C4Alkyl radical, C6–C10Aryl, 5-8 membered heteroaryl;
R6is hydrogen, halogen, cyano, nitro, C2–C6Ester group, C2–C6A sulfonate group and a substituted or unsubstituted of: c1–C4Alkyl radical, C2–C4Alkenyl radical, C2–C4Alkynyl, C3–C6Cycloalkyl, 4-8 membered heterocyclyl, C6–C10Aryl, 5-8 membered heteroaryl, C1–C4Alkoxy radical, C2–C4Alkenyloxy radical, C2–C4Alkynyloxy, C3–C6Cycloalkyl oxy, C3–C6Cycloalkyl oxy, C6–C10Aryloxy, 5-8 membered heteroaryloxy, C1–C4Alkylthio radical, C2–C4Alkenylthio radical, C2–C4Alkynylthio, C3–C6Cycloalkylthio radical, C6–C10Arylthio, 5-8 membered heteroarylthio; wherein said substitution is by one or more groups selected from the group consisting of: halogen, cyano, nitro, C2–C6Ester group, C2–C6Sulfonate group, C1–C4Alkyl radical, C2–C4Alkenyl radical, C2–C4Alkynyl, C3–C5Cycloalkyl radical, C6–C10Aryl, 5-8 membered heteroaryl, halo C1–C4Alkyl, halo C2–C4Alkenyl, halo C2–C4Alkynyl, halo C3–C5Cycloalkyl, halo C6–C10Aryl, halo 5-8 membered heteroaryl;
R7、R9each independently selected from hydrogen, halogen, cyano, nitro, carboxyl, C2–C6Ester group, C2–C6A sulfonate group and a substituted or unsubstituted of: c1–C4Alkyl radical, C2–C4Alkenyl radical, C2–C4Alkynyl, C6–C10Aryl radical, C1–C4Alkoxy radical, C2–C4Alkenyloxy radical, C2–C4Alkynyloxy, C3–C5Cycloalkyl oxy, C6–C10Aryloxy, 5-8 membered heteroaryloxy, C1–C6Alkylthio radical, C2–C6Alkenylthio radical, C2–C6Alkynylthio, C3–C6Cycloalkyl sulfurBase, C6–C10Arylthio, 5-8 membered heteroarylthio; wherein said substitution is by one or more groups selected from the group consisting of: halogen, cyano, nitro, C1-C4Alkyl, halo C1-C4An alkyl group;
R8、R10each independently hydrogen, halogen, and substituted or unsubstituted: c1–C4Alkyl radical, C2–C4Alkenyl radical, C1–C4Alkoxy radical, C2–C4An alkenyloxy group; wherein said substitution is by one or more groups selected from the group consisting of: halogen, cyano;
wherein R is12Is substituted or unsubstituted C1–C4Alkyl radical, C2–C4Alkenyl radical, C6–C10Aryl, 5-8 membered heteroaryl.
In another preferred embodiment, X is N or CR11(ii) a Wherein R is11Hydrogen, halogen, cyano, nitro;
R1is hydrogen, halogen, cyano, nitro, C2–C6Ester group, C2–C6A sulfonate group and a substituted or unsubstituted of: c1–C6Alkyl radical, C2–C6Alkenyl radical, C2–C6Alkynyl, C3–C6Cycloalkyl, 4-8 membered heterocyclyl, C6–C10Aryl, 5-8 membered heteroaryl, -CONHR12；
R1'Hydrogen, halogen, cyano and substituted or unsubstituted groups: 4-8 membered heterocyclic group, C6–C10Aryl, 5-8 membered heteroaryl, -CONHR12(ii) a Wherein R is12Is substituted or unsubstituted C1–C4Alkyl radical, C2–C4Alkenyl radical, C6–C10Aryl, 5-8 membered heteroaryl; wherein said substitution is by one or more groups selected from the group consisting of: halogen, cyano, C1–C4Alkyl, halo C1–C3An alkyl group;
R3、R4each independently hydrogen or a substituted or unsubstituted group selected from: c1–C6Alkyl radical, C2–C6Alkenyl radical, C6–C10An aryl group; wherein said substitution is by one or more groups selected from the group consisting of: halogen, cyano, nitro, C1–C4Alkyl radical, C2–C4Alkenyl radical, C6–C10Aryl, 5-8 membered heteroaryl, halo C1–C4Alkyl, halo C2–C4Alkenyl, halo C6–C10Aryl, halo 5-8 membered heteroaryl;
wherein R is12Is substituted or unsubstituted C1–C4Alkyl radical, C2–C4Alkenyl radical, C6–C10Aryl, 5-8 membered heteroaryl.
In another preferred embodiment, R1'Hydrogen and substituted or unsubstituted groups: c6–C10Aryl, 5-8 membered heteroaryl; wherein said substitution is by one or more groups selected from the group consisting of: halogen, cyano, C1–C4Alkyl, halo C1–C4An alkyl group.
In another preferred embodiment, the compound has a structure shown as a general formula (IV),
Figure BDA0003352346640000061
in the formula (I), the compound is shown in the specification,
x is N or CR11(ii) a Wherein R is11Hydrogen, halogen, cyano, nitro;
R1is hydrogen, halogen, cyano, nitro, C2–C6Ester group, C2–C6A sulfonate group and a substituted or unsubstituted of: c1–C6Alkyl radical, C2–C6Alkenyl radical, C2–C6Alkynyl, C3–C6Cycloalkyl, 4-8 membered heterocyclyl, C6–C10Aryl, 5-8 membered heteroaryl, -CONHR12(ii) a Wherein R is12Is substituted or unsubstituted C1–C4Alkyl radical, C2–C4Alkenyl radical, C6–C10Aryl, 5-8 membered heteroaryl; wherein said substitution is by one or more groups selected from the group consisting of: halogen, cyano, nitro, C2–C6Ester group, C2–C6Sulfonate group, C1–C4Alkyl radical, C2–C4Alkenyl radical, C2–C4Alkynyl, C3–C5Cycloalkyl radical, C6–C10Aryl, 5-8 membered heteroaryl, halo C1–C3Alkyl, halo C2–C4Alkenyl, halo C2–C4Alkynyl, halo C3–C5Cycloalkyl, halo C6–C10Aryl, halogenated 5-8 membered heteroaryl, C1–C4Alkoxy radical, C6–C10Aryloxy, 5-8 membered heteroaryloxy;
R2hydrogen and substituted or unsubstituted groups: c1–C6Alkyl radical, C2–C6Alkenyl radical, C2–C6Alkynyl, C3–C6Cycloalkyl, 4-8 membered heterocyclyl, C6–C10Aryl, 5-8 membered heteroaryl, -COR13、–CONHR13、–NHCOR13(ii) a Wherein R is13Is substituted or unsubstituted C1–C4Alkyl radical, C2–C4Alkenyl radical, C3–C6Cycloalkyl radical, C6–C10Aryl, 5-8 membered heteroaryl; wherein said substitution is by one or more groups selected from the group consisting of: halogen, cyano, nitro, C2–C6Ester group, C2–C6Sulfonate group, C1–C4Alkyl radical, C2–C4Alkenyl radical, C2–C4Alkynyl, C3–C5Cycloalkyl radical, C6–C10Aryl, 5-8 membered heteroaryl, halo C1–C4Alkyl, halo C2–C4Alkenyl, halo C2–C4Alkynyl, halo C3–C5Cycloalkyl, halo C6–C10Aryl, halogenated 5-8 membered heteroaryl, C1–C4Alkoxy radical, C6–C10Aryloxy radical, C1–C4Alkylamino radical, C6–C10Arylthio group, C1–C4An alkylthio group;
R3、R4each independently hydrogen or a substituted or unsubstituted group: c1–C6Alkyl radical, C2–C6Alkenyl radical, C6–C10An aryl group; wherein said substitution is by one or more groups selected from the group consisting of: halogen, cyano, C1–C4An alkyl group;
R5is hydrogen, halogen, cyano, nitro, C2–C6An ester group;
R7、R9each independently of the others is hydrogen, halogen, cyano, nitro, C2–C6An ester group and a substituted or unsubstituted group: c1–C4Alkyl radical, C2–C4Alkenyl radical, C2–C4Alkynyl, C6–C10Aryl radical, C1–C4Alkoxy radical, C2–C4Alkenyloxy radical, C2–C4Alkynyloxy, C6–C10Aryloxy, 5-8 membered heteroaryloxy, C1–C6Alkylthio radical, C2–C6Alkenylthio radical, C2–C6Alkynylthio, C6–C10Arylthio, 5-8 membered heteroarylthio; wherein said substitution is by one or more groups selected from the group consisting of: halogen, cyano, nitro.
In another preferred embodiment, R1Is hydrogen, halogen, cyano, nitro, C2–C6Ester group, C2–C6A sulfonate group and a substituted or unsubstituted of: c1–C6Alkyl radical, C2–C6Alkenyl radical, C2–C6Alkynyl, 4-8 membered heterocyclyl, C6–C10Aryl, 5-8 membered heteroaryl;
R2hydrogen and substituted or unsubstituted groups: c1–C6Alkyl radical, C2–C6Alkenyl radical, C2–C6Alkynyl, C3–C6Cycloalkyl, 4-8 membered heterocyclyl, C6–C10Aryl, 5-8 membered heteroaryl, -COR13、–CONHR13、–NHCOR13(ii) a Wherein R is13Is substituted or unsubstituted C1–C4Alkyl radical, C2–C4Alkenyl radical, C3–C6Cycloalkyl radical, C6–C10Aryl, 5-8 membered heteroaryl;
R6is hydrogen, halogen, cyano, nitro, C2–C6Ester group, C2–C6A sulfonate group and a substituted or unsubstituted of: c1–C4Alkyl radical, C2–C4Alkenyl radical, C2–C4Alkynyl, C3–C6Cycloalkyl radical, C6–C10Aryl, 4-8 membered heterocyclic group, C1–C4An alkoxy group; wherein said substitution is by one or more groups selected from the group consisting of: halogen, cyano, C1–C4Alkyl radical, C6–C10Aryl, 5-8 membered heteroaryl, halo C6–C10Aryl, halo 5-8 membered heteroaryl;
R7、R9each independently hydrogen, halogen, cyano, nitro, carboxyl, and substituted or unsubstituted: c6–C10Aryl radical, C1–C4Alkoxy radical, C6–C10Aryloxy, 5-8 membered heteroaryloxy, C1–C6An alkylthio group; wherein said substitution is by one or more groups selected from the group consisting of: halogen, cyano;
R8、R10each independently hydrogen, halogen.
In another preferred embodiment, the compound has a structure represented by the general formula (V),
Figure BDA0003352346640000071
in the formula (I), the compound is shown in the specification,
R1is hydrogen, halogen, cyano, C2–C6An ester group and a substituted or unsubstituted group: c1–C6Alkyl radical, C2–C6Alkenyl radical, C2–C6Alkynyl, 4-8 membered heterocyclyl, C6–C10Aryl, 5-8 membered heteroaryl; wherein said substitution is by one or more groups selected from the group consisting of: halogen, cyano, nitro, C2–C6Ester group, C1–C4Alkyl radical, C2–C4Alkenyl radical, C2–C4Alkynyl, C6–C10Aryl, 5-8 membered heteroaryl, halo C1–C3Alkyl, halo C2–C4Alkenyl, halo C2–C4Alkynyl, halo C6–C10Aryl, halogenated 5-8 membered heteroaryl, C1–C4Alkoxy radical, C6–C10An aryloxy group;
R2hydrogen and substituted or unsubstituted groups: c1–C6Alkyl radical, C2–C6Alkenyl radical, C2–C6Alkynyl, C3–C6Cycloalkyl, 4-8 membered heterocyclyl, C6–C10Aryl, 5-8 membered heteroaryl, -COR13、–CONHR13、–NHCOR13(ii) a Wherein R is13Is substituted or unsubstituted C1–C4Alkyl radical, C2–C4Alkenyl radical, C3–C6Cycloalkyl radical, C6–C10Aryl, 5-8 membered heteroaryl; wherein said substitution is by one or more groups selected from the group consisting of: halogen, cyano, C2–C6Ester group, C1–C4Alkyl radical, C2–C4Alkenyl radical, C2–C4Alkynyl radical、C3–C5Cycloalkyl radical, C6–C10Aryl, 5-8 membered heteroaryl, halo C1–C4Alkyl, halo C2–C4Alkenyl, halo C2–C4Alkynyl, halo C3–C5Cycloalkyl, halo C6–C10Aryl, halogenated 5-8 membered heteroaryl, C1–C4Alkoxy radical, C6–C10Aryloxy radical, C1–C4Alkyl amine, C6–C10Arylthio group, C1–C4An alkylthio group;
R6is hydrogen, halogen, cyano, nitro, C2–C6An ester group and a substituted or unsubstituted group: c1–C4Alkyl radical, C3–C6Cycloalkyl radical, C6–C10Aryl (I-172, 165), C1–C4An alkoxy group; wherein said substitution is by one or more groups selected from the group consisting of: halogen, C1–C4An alkyl group;
R7，R9each independently selected from the group consisting of: hydrogen, halogen, cyano, carboxyl and substituted or unsubstituted: c6–C10Aryl radical, C1–C4Alkoxy radical, C6–C10Aryloxy radical, C1–C6Alkylthio, 5-8 membered heteroarylthio; wherein said substitution is by one or more groups selected from the group consisting of: halogen, C1-C4An alkyl group.
In another preferred embodiment, R1Selected from hydrogen, halogen, cyano, C2–C6An ester group and a substituted or unsubstituted group: c2–C6Alkenyl radical, C6–C10Aryl, 5-8 membered heteroaryl; wherein said substitution is by one or more groups selected from the group consisting of: halogen, cyano, nitro, C2–C6Ester group, C1–C4Alkyl radical, C6–C10Aryl, halo C1–C3Alkyl radical, C1–C4Alkoxy radical, C6–C10An aryloxy group;
R2hydrogen and substituted or unsubstituted groups: c1–C6Alkyl radical, C2–C6Alkenyl radical, C2–C6Alkynyl, C3–C6Cycloalkyl, 4-8 membered heterocyclyl, C6–C10Aryl, 5-8 membered heteroaryl, -COR13、–CONHR13、–NHCOR13(ii) a Wherein R is13Is substituted or unsubstituted C1–C4Alkyl radical, C2–C4Alkenyl radical, C3–C6Cycloalkyl radical, C6–C10Aryl, 5-8 membered heteroaryl; wherein said substitution is by one or more groups selected from the group consisting of: halogen, cyano, C2–C6Ester group, C1–C4Alkyl radical, C2–C4Alkenyl radical, C2–C4Alkynyl, C3–C5Cycloalkyl radical, C6–C10Aryl, 5-8 membered heteroaryl, halo C1–C4Alkyl, halo 5-8 membered heteroaryl, C1–C4Alkoxy radical, C6–C10Aryloxy radical, C1–C4Alkylamino radical, C6–C10Arylthio group, C1–C4An alkylthio group.
In another preferred embodiment, R1Selected from hydrogen, halogen, cyano, C2–C6An ester group and a substituted or unsubstituted group: phenyl radical, C2–C6Alkenyl, 5-8 membered heteroaryl; wherein said substitution is by one or more groups selected from the group consisting of: halogen, cyano, nitro, C2–C6Ester group, C1–C4Alkyl, phenyl, halo C1–C3Alkyl radical, C1–C4Alkoxy radical, C6–C10An aryloxy group.
In another preferred embodiment, R1Is substituted or unsubstituted phenyl or 5-8 membered heteroaryl. In another preferred embodiment, the 5-8 membered heteroaryl is furan, thiophene.
In another preferred embodiment, the halogen is F or Cl.
In another preferred embodiment, R1Selected from the group consisting of: F. CN, vinyl, phenyl, halogenated phenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl and thienyl.
In another preferred embodiment, R2Is a substituted or unsubstituted group: c1–C6Alkyl radical, C2–C6Alkenyl radical, C2–C6Alkynyl, C3–C6Cycloalkyl, 4-8 membered heterocyclyl, phenyl, 5-8 membered heteroaryl, -COR13、–CONHR13、–NHCOR13(ii) a Wherein said substitution is by one or more groups selected from the group consisting of: halogen, cyano, C2–C6Ester group, C1–C4Alkyl radical, C2–C4Alkenyl radical, C2–C4Alkynyl, C3–C5Cycloalkyl radical, C6–C10Aryl, 5-8 membered heteroaryl, halo C1–C4Alkyl, halo 5-8 membered heteroaryl, C1–C4Alkoxy radical, C6–C10Aryloxy radical, C1–C4Alkylamino radical, C6–C10Arylthio group, C1–C4An alkylthio group.
In another preferred embodiment, R2Is substituted or unsubstituted C6–C10Aryl or 5-8 membered heteroaryl.
In another preferred embodiment, R2Is substituted or unsubstituted phenyl or 5-6 membered heteroaryl.
In another preferred embodiment, the 5-6 membered heteroaromatic ring is furan, pyridine, thiophene, thiazole.
In another preferred embodiment, the substitution is halo, trifluoromethyl or cyano.
In another preferred embodiment, the halo is fluoro or chloro.
In another preferred embodiment, R6Selected from the group consisting of: hydrogen, halogen,Cyano, methyl, trifluoromethyl, tert-butyl, methoxy, nitro, phenyl, benzyl, 4-fluorophenyl, 4-chlorophenyl, cyclopropyl.
In another preferred embodiment, R6Is halogen, substituted or unsubstituted alkyl.
In another preferred embodiment, R6Is halogen and trifluoromethyl.
In another preferred embodiment, R6Is Br, F, Cl, CH3、CF3。
In another preferred embodiment, R6F, Br or Cl.
In another preferred embodiment, R7、R9Each independently hydrogen, halogen, nitro, cyano.
In another preferred embodiment, R7Is hydrogen or halogen.
In another preferred embodiment, R7H, Cl or Br.
In another preferred embodiment, R9Selected from the group consisting of: H. cl, Br, CN, OCH3、OSCH3、COOCH3Phenyl, 4-chlorophenyl, 4-methoxyphenyl, thiophen-2-yl, CH2Ph。
In another preferred embodiment, R9Is H, halogen or CN.
In another preferred embodiment, R9H, F, Cl, Br or CN.
In another preferred embodiment, X is selected from the group consisting of: n, CH, CCl, CCN, CCH2、CPh、CBr、CNO2。
In another preferred embodiment, the compound is selected from the group consisting of: compounds I-1 to I-192 in Table I.
In another preferred embodiment, the compound is selected from the group of table I: 1-14,1-30,1-52,1-56,1-57,1-58,1-62,1-63,1-64,1-65,1-66,1-67,1-68,1-78,1-79,1-80,1-81,1-82,1-83,1-84,1-85,1-86,1-87,1-88,1-89,1-90,1-91,1-97,1-98,1-99,1-100,1-101,1-102,1-103,1-104,1-155,1-156,1-173,1-178,1-180,1-182,1-189.
In another preferred embodiment, the compound is 1-52, 1-97, 1-98, 1-99, 1-100, 1-101, 1-102, 1-103, 1-104 of Table I.
Preferably, the compound is 1-52 in table I.
In a second aspect of the present invention, there is provided a pesticidal composition comprising (1) a compound having a structure represented by the general formula (I) described in the first aspect of the present invention, an optical isomer, a cis-trans isomer, or an agriculturally pharmaceutically acceptable salt thereof; and (2) an agriculturally pharmaceutically acceptable carrier or excipient.
In another preferred embodiment, the pesticide composition further comprises an agriculturally acceptable adjuvant.
In another preferred embodiment, component (a) comprises 0.001-99.99 wt% of the total weight of the pharmaceutical composition; preferably 0.01 to 99.9 wt%; more preferably from 0.05 to 90 wt%.
Preferably, when necessary, one or more carriers acceptable in pesticide preparations can be added into the pesticide composition, wherein the carriers comprise conventional diluents, excipients, fillers, binders, wetting agents, absorption promoters, surfactants, lubricants, stabilizers, antifoaming agents, diatomaceous earth and the like in pesticide preparations; the dosage forms of the prepared medicine are also various, and can be powder, emulsion, water aqua, granules, corrosion inhibitor, effervescent tablets and the like.
Preferably, the mass percentage of the compound of the invention in the composition is 1% -90%, and the proportion of the compound of the invention and the pesticide is 1% -99% -1%; can be directly mixed with water and sprayed, the preparation of the composition comprises agriculturally acceptable solvents and emulsifiers, cosolvent and synergist and the like, and the preparation processed by the composition is selected from sustained-release agents, powders, microcapsule suspending agents, dispersible liquid preparations, dispersible solid preparations, seed treatment emulsions, aqueous emulsions, granules, microemulsions, oil agents, seeds coated with pesticides, suspoemulsions, soluble concentrates, poison cereals, aerosols, block poisons, sustained-release blocks, concentrated poisoned baits, capsule suspending agents, dispersible concentrates, emulsifiable concentrates, electrostatic sprays, oil-in-oil mixtures, seed treatment agents, oil-in-water emulsions, aerosol cans, fine granules, aerosol candles, aerosol cans, aerosol sticks, aerosol tablets, aerosol pills, particulate poisoned baits, gas generating agents, ointments, hot fogging agents, solid/liquid mixing preparations, liquid/liquid mixing preparations, cold fogging agents, solid/solid mixing preparations, The coating agent is any one of medicinal paint, seed treatment liquid, microgranule, oil suspension, oil solution, oil dispersible powder, paste, sheet poison bait, concentrated colloid, sprinkling agent, stick, seed coating agent, poison bait, smearing agent, small block poison bait, suspending agent, suspending emulsion, water soluble granule, soluble concentrated agent, film forming oil solution, tablet, tracing powder, ultra-low volume liquid and steam releasing agent.
In another preferred embodiment, the pesticide composition further comprises an insecticide selected from the group consisting of: chlorpyrifos, diazinon, acetamiprid, emamectin benzoate, abamectin, spinosad, fenvalerate, cypermethrin, Beta-cyfluthrin, Lambda-cyhalothrin, permethrin, cyfluthrin, deltamethrin, fenpropathrin, Beta-cyfluthrin, Lambda-cyhalothrin, permethrin, allethrin, cyfluthrin, bifenthrin, permethrin, flumethrin, cyhalothrin, imidacloprid, acetamiprid, nitenpyram, imidacloprid, thiamethoxam, dinotefuran, cotinin, dinotefuran, diflubenzuron, chlorbenzuron, fluazuron, flufenoxuron, pyriduron, lufenuron, chlorfluazuron, noviflumuron or noviflumuron, CAS number 121451-3, novaluron, cyhalofenoxuron, and so, etc., cyhalofenoxuron, etc., cyhalothrin, etc, Fluorobrene, Baysir 6874 {1- [ (3, 5-dichloro-4) 4-nitrophenoxyphenyl 3-3- (2-chlorophenyl) -urea }, Baysir-8514 [1- (4-trifluoromethoxyphenyl) -3- (2-chlorophenyl) -urea }, chlorfluazuron, Bistrifulon Bistrifluron, furfenozide, tebufenozide, chlorfenapyr, methoxyfenozide, chromafenozide, cyfenozide, dimethoate, omethoate, dichlorvos, acephate, triazophos, quinalphos, pyridaphenthion, chlorzofos, tetrafenozide, fenozide, fenobucarb, proparacarb, benfuracarb, fenobucarb, proparacarb, carbosulfan, fenitrole, fenitrothion, hexythiazox, fenpyroximate, pyridaben, clofentezine, propargite, diafenthiuron, and the like, Benfuracarb, pymetrozine, spirodiclofen, spirotetramat, butene-fipronil, azocyclotin, buprofezin, fenamiphos, fipronil, monosultap, dimehypo, chlorantraniliprole, flubendiamide, cyantraniliprole, tolfenpyrad, tebufenpyrad, chlorfenapyr, pyrazinone, etoxazole, tebufenpyrad, pyridaben, pyriproxyfen, emamectin.
In the third aspect of the invention, the invention provides a compound with the structure shown in the general formula (I) in the first aspect of the invention, an optical isomer, a cis-trans isomer or an agriculturally and pharmaceutically acceptable salt thereof or the application of the pesticide composition in the second aspect of the invention,
(i) for the preparation of insecticides; or
(ii) Is used for preventing and controlling agricultural and forestry and horticultural plant insect pests.
Preferably, the agricultural and forestry and horticultural plant plants include rice, wheat, barley, oats, corn, sorghum, sweet potato, cassava, soybean, sweet broad bean, pea, mung bean, small bean, cotton, silkworm, peanut, rape, sesame, sunflower, sugar beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal, tobacco, tomato, capsicum, radish, cucumber, cabbage, celery, mustard tuber, beet, rape, shallot, garlic, watermelon, melon, cantaloupe, papaya, fruit, tea, potherb, bamboo shoot, hop, rice, pepper, apple, banana, citrus, peach, papaya, orchid, bonsai.
Preferably, the pesticide controls the following pests: red spider, east Asian migratory locust, black-spotted locust, Chinese rice locust, Japanese yellow-back locust, Gryllotalpa orientalis, rice thrips, thrips tabaci, thrips oryzae, green-house thrips, green-house powdery mildew, tobacco powder-forming herbs, butterfly black-tail, butterfly of green-leaf, butterfly of cotton, mackerel , brown-flying FENG, FENG of white back, FENG of gray, sugarcane-flat-horn planthopper, cotton aphid, binary aphid, pipe aphid, peach aphid, green sorghum aphid, radish aphid, mealybug, stinkbug, pear gecko, white wax worm, red-wax bug, red-green-bulb worm, pear-net, banana net, small-horn bug, stinkbug, small-leaved fly, sand fly, rice-wing, spider, brown rice, rice moth, black-bug, black-eared moth, black-eared caterpillar, black-leaf moth, black-leaved rice moth, black-leaved sweetflag, black-leaf moth, black-leaved sweetflag, green-leaf moth, black-leaved sweetflag, green-leaf-leaved sweetflag, green-leaved sweetflag, black-leaved sweetflag, green pepper, black-like sweetflag, red bell, black-leaved sweetflag, black-like sweetflag, red bell, black-leaved sweetflag, red bell, black-green pepper, black-leaved sweetflag, black-leaved sweetgum, red bell, black-green pepper, red bell, black-leaved sweetgum, red bell, black-green pepper, red bell, black-leaved sweetgum, red bell, black-green pepper, red bell, black-green pepper, red bell, black-green pepper, red bell, black-green pepper, black-green pepper, red pepper, black-green pepper and black pepper, black-green pepper and black pepper, black, Plutella xylostella, carposina niponensis, carposina glycines, carposina niponensis, codling borer, pink moth, striped rice borer, pink borer, yellow rice borer, rice leaf roller, striped rice borer, cotton leaf borer, peach moth, armyworm, prodenia litura, rice snout moth, cotton small bridgehead, beet armyworm, sesamia inferens, cotton bollworm, diamond-back moth, black cutworm, yellow cutworm, pirate moth, gypsy moth, sweet potato hawkmoth, bean hawkmoth, straight-line rice skipper, cryptophysalis grain, orange butterfly, jade belt moth, cabbage butterfly, red butterfly, ramie yellow butterfly, lilyturf beetle, pink beetle, black beetle, yellow beetle, black beetle, etc, Aerugo Liriomys aeruginosa, black tortoise, big Holotrichia parallela, white longicorn, star longicorn, orange brown longicorn, peach red neck longicorn, apes petiolatus, yellow-keeping melon, yellow flea beetle, mung bean, pea, broad bean, corn, rice, wheat leaf bee, pear fruit bee, yellow stripe wasp, armyworm white fly, bollworm-like fly, cotton bollworm tooth wasp, borer black spot wasp, mosquito, fly, horsefly, red mud worm, yellow mud worm, rice gall mosquito, citrus fruit fly, melon fly, leaf ash fly, American fly, bean stem black fly, wheat stem fly, seed fly, onion, radish fly, umbrella skirt fly, corn borer and yellow fly.
In a fourth aspect of the present invention, there is provided a method for controlling pests by applying a compound having a structure represented by the general formula (I) according to the first aspect of the present invention, an optical isomer, a cis-trans isomer or an agriculturally and pharmaceutically acceptable salt thereof, or a pesticidal composition according to the second aspect of the present invention to the environment, soil or agricultural and forestry plants and horticultural plants to be controlled.
In another preferred embodiment, the insect pest is caused by an insect selected from the group consisting of: diamondback moth and armyworm.
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 application researches extensively and deeply to develop a series of diamide compounds containing cyclic amino acids, which have insecticidal activity, have obvious inhibition effect on diamond back moths and armyworms and can be used as pesticides in agricultural production.
Term(s) for
In the present invention, the term "halogen" means fluorine, chlorine, bromine or iodine.
The term "halo" refers to a group substituted with one or more of the above halogen atoms, which may be the same or different, such as difluoromethyl, pentachloroethyl, heptafluoroisopropyl, or the like.
The term "C1–C6"means having 1,2, 3,4,5, or 6 carbon atoms, and so forth. "4-8 membered" means having 4-8 ring atoms, and so on.
The term "C1–C6Alkyl "means a straight or branched chain alkyl group having 1 to 6 carbon atoms, such as methyl, ethyl, isopropyl, tert-butyl or the like.
The term "C2–C6Alkenyl "means a straight or branched chain alkenyl group having 2 to 6 carbon atoms, such as vinyl, allyl, 1-propenyl, isopropenyl, 1-butenyl, 2-butenyl, or the like.
The term "C2–C6Alkynyl "means a straight or branched chain alkynyl group having 2 to 6 carbon atoms, such as ethynyl, propynyl or the like.
The term "C3–C6Cycloalkyl "refers to a cyclic alkyl group having 3 to 6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or the like.
The term "4-8 membered heterocyclyl" refers to a 4-8 membered cyclic group containing at least one ring heteroatom (e.g., N, O or S), such as morpholinyl, hexahydroisoindolyl, tetrahydrofuranyl, tetrahydropyrrolyl, and the like. 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 "C6–C10Aryl "refers to an aromatic ring group having 6 to 10 carbon atoms containing no heteroatoms in the ring, such as phenyl, naphthyl, and the like.
The term "5-8 membered heteroaryl" refers to a 5-8 membered heteroaromatic ring group containing one or more heteroatoms on the ring, such as pyrrolyl, furanyl, thienyl, pyrazolyl, thiazolyl, imidazolyl, oxazolyl, isoxazolyl, pyridyl, pyranyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzindole, benzofuran, benzimidazolyl and the like.
The term "C1–C4Alkoxy "means a straight or branched chain alkoxy group having 1 to 4 carbon atoms, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy or the like. "alkenyloxy", "alkynyloxy", "cycloalkyloxy", "aryloxy", "heteroaryloxy", and the like.
The term "C1–C4Alkylthio "means a straight or branched chain alkylthio group having 1 to 4 carbon atoms, such as methylthio, ethylthio, isopropylthio, tert-butylthio or the like. "alkenylthio", "alkynylthio", "cycloalkylthio", "arylthio", "heteroarylthio", and the like.
The term "C1–C4Alkylamino "refers to a straight or branched chain alkylamino group having 1 to 4 carbon atoms, such as methylamino, ethylamino, isopropylamino, tert-butylamino, or the like. "alkenylamino", "alkynylamino", "cycloalkylamino", "arylamino", "heteroarylamino" and the like.
Insecticidal Activity of the active substances according to the invention
The term "active substance according to the invention" or "active compound according to the invention" means a compound of the structure shown by the general formula (I) or an agriculturally pharmaceutically acceptable salt. It contains cyclic amino acid structure, has obvious pesticidal activity, wide pesticidal spectrum and high stability.
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 pesticide. 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 compound has better control effect on diamondback moth and armyworm.
Pesticide compositions containing active substances according to the invention
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 by known methods, for example by mixing the active compounds with extenders, that is, liquid or liquefied gas or solid diluents or carriers, and optionally 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 a liquid solvent is used as the diluent or carrier, 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 polar solvents such as dimethylformamide, 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, dolomite, synthetic granules of inorganic and organic meals, and granules of organic materials, such as sawdust, coconut shells, corn cobs and tobacco stalks, among others.
Nonionic and anionic emulsifying trains may be used as emulsifiers and/or foam formers. Such as polyoxyethylene-fatty acid esters, polyoxyethylene-fatty alcohol ethers, alkylaryl polyethylene glycol ethers, alkylsulfonates, alkylsulfates, arylsulfonates 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; 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 control agents, etc., or in the use forms prepared from these preparations. Insecticides include, for example, phosphates, carbamates, chlorinated hydrocarbons, and substances produced by microorganisms, such as avermectins, etc., and fungicides include strobilurins, amides, triazoles, etc.
Furthermore, the active compounds according to the invention can also be present in their commercial preparations in a mixture with synergists, which are compounds which increase the action of the active compounds, or in the use forms prepared from these preparations, it being possible for no synergists to be 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 of the invention, based on the total weight of the fungicide composition. The concentration of the active compound in the commercial preparations or dosage forms to be used can vary within wide limits. The concentration of active compound in the dosage form to be used may be from 0.0000001 to 100% (g/v), preferably between 0.0001 and 1% (g/v).
Process for the preparation of the compounds of the invention
The cyclic amino acid-containing diamide compounds of the 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, and the like, 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.
The invention synthesizes the diamide compounds containing the cyclic amino acid shown in the general formulas (I) - (V), and the preparation method is simple and easy to implement, simple to operate, easy to purify the product, lower in cost and improved in stability. The diamide compound containing cyclic amino acid has obvious insecticidal activity proved by tests, and is used for preventing and treating insect pests of crops, fruit trees, Chinese herbal medicines and flowers.
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. The experimental procedures, in which specific conditions are not noted in the following examples, are generally carried out under conventional conditions or conditions recommended by the manufacturers. Unless otherwise indicated, percentages and parts are by weight.
Example 1: preparation of 3-bromo-1- (3-chloropyridin-2-yl) -N- (1- (phenylcarbamoyl) cyclohexyl) -1H-pyrazole-5-carboxamide (Compound I-1)
1.1 preparation of tert-butyl (1- (phenylcarbamoyl) cyclohexyl) carbamate
Figure BDA0003352346640000171
2.43g (10mmol) of 1- (tert-butoxycarbonyl) amino) cyclohexane-1-carboxylic acid, 100mL of methylene chloride, 0.91g (9.5mmol) of aniline, 3.03g (30mmol) of triethylamine and 5.72g (11mmol) of benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate were successively charged into a 250mL three-necked flask. After 4h reaction at room temperature, 100mL of water was added. The organic phase is separated off and the aqueous phase is extracted twice with 50mL of dichloromethane. The combined organic phases were dried over anhydrous sodium sulfate and the solvent was removed by rotary evaporation. The crude product was purified by column chromatography to give 2.22g of a white solid in 73.5% yield.
1.21 preparation of amino-N-phenylcyclohexane-1-carboxamide
Figure BDA0003352346640000172
2.22g (7.3mmol) of t-butyl (1- (phenylcarbamoyl) cyclohexyl) carbamate, 80mL of dichloromethane, and 10mL of trifluoroacetic acid were sequentially charged into a 250mL three-necked flask. After reacting for 2h at room temperature, the solvent was removed by rotary evaporation to give 2.28g of a product as a yellow oily liquid with a yield of 98.4%. The reaction is directly carried out without further treatment.
Preparation of 33-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carbonyl chloride
Figure BDA0003352346640000181
2.21g (7.3mmol) of 3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxylic acid and 50mL of methylene chloride were successively placed in a 500mL three-necked flask, and 1.08g (8.5mmol) of oxalyl chloride was added dropwise to the flask in an ice bath. After reacting for 2h at room temperature, the solvent is removed by rotary evaporation to obtain 2.30g of a product yellow oily liquid, the yield is 98.2%, and the next reaction is directly carried out without further treatment.
Preparation of 43-bromo-1- (3-chloropyridin-2-yl) -N- (1- (phenylcarbamoyl) cyclohexyl) -1H-pyrazole-5-carboxamide
Figure BDA0003352346640000182
2.28g (6.9mmol) of 1-amino-N-phenylcyclohexane-1-carboxamide, 80mL of dichloromethane and 2.79g (27.6mmol) of triethylamine are successively introduced into a 250mL three-necked flask, and a solution (30mL) of 3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carbonyl chloride (2.30g, 7.2mmol) in dichloromethane is added dropwise under ice. After 4h reaction at room temperature, 100mL of water was added. The organic phase is separated off and the aqueous phase is extracted twice with 50mL of dichloromethane. The combined organic phases were dried over anhydrous sodium sulfate, the solvent was removed by rotary evaporation and the crude product was purified by column chromatography to give the product as a white solid 2.53g with 73.0% yield.
1H NMR(400MHz,DMSO-d6)δ9.49(s,1H),8.71(s,1H),8.37(dd,J＝4.7,1.4Hz,1H),8.10(dd,J＝8.0,1.4Hz,1H),7.57(dd,J＝8.0,4.7Hz,1H),7.48–7.42(m,2H),7.41(s,1H),7.22(t,J＝7.8Hz,2H),7.01(t,J＝7.2Hz,1H),2.36–2.20(m,2H),2.04–1.91(m,2H),1.73–1.52(m,4H),1.49–1.36(m,2H).
Compounds I-2, I-4, I-6, I-7, I-8, I-10, I-11, I-12 were each synthesized according to the procedure of example 1, and the corresponding NMR chart is shown in Table II.
Example 2: preparation of 3-bromo-1- (3-chloropyridin-2-yl) -N- (1- (phenylcarbamoyl) cyclopentyl) -1H-pyrazole-5-carboxamide (Compound I-3)
2.1 preparation of tert-butyl (1- (phenylcarbamoyl) cyclopentyl) carbamate
Figure BDA0003352346640000191
The synthesis of the target compound was similar to 1.1, except that 1- (tert-butoxycarbonyl) amino) cyclopentane-1-carboxylic acid was used as the starting material instead of 1- (tert-butoxycarbonyl) amino) cyclohexane-1-carboxylic acid. The product was a white solid in 70.1% yield.
Preparation of 21-amino-N-phenylcyclopentane-1-carboxamide
Figure BDA0003352346640000192
The synthesis of the target compound was similar to 1.2, except that the starting material was tert-butyl (1- (phenylcarbamoyl) cyclopentyl) carbamate instead of tert-butyl (1- (phenylcarbamoyl) cyclohexyl) carbamate. The product was a yellow oily liquid with a yield of 98.3%. The reaction is directly carried out without further treatment.
Preparation of 33-bromo-1- (3-chloropyridin-2-yl) -N- (1- (phenylcarbamoyl) cyclopentyl) -1H-pyrazole-5-carboxamide
Figure BDA0003352346640000193
The synthesis of the target compound was similar to 1.4, except that 1-amino-N-phenylcyclopentane-1-carboxamide was used as the starting material instead of 1-amino-N-phenylcyclohexane-1-carboxamide. The product was a white solid in 74.1% yield.
1H NMR(400MHz,DMSO-d6)δ9.48(s,1H),8.84(s,1H),8.38(dd,J＝4.7,1.4Hz,1H),8.13(dd,J＝8.0,1.4Hz,1H),7.57(dd,J＝8.0,4.7Hz,1H),7.54–7.45(m,3H),7.25(t,J＝7.8Hz,2H),7.01(t,J＝7.2Hz,1H),2.22–2.10(m,2H),2.02–1.90(m,2H),1.76–1.58(m,4H).
Example 3: preparation of 3-bromo-1- (3-chloropyridin-2-yl) -N- (1- (phenylcarbamoyl) cyclobutyl) -1H-pyrazole-5-carboxamide (Compound I-5)
3.1 preparation of tert-butyl (1- (phenylcarbamoyl) cyclobutyl) carbamate
Figure BDA0003352346640000194
The synthesis of the target compound was similar to 1.1, except that 1- (tert-butoxycarbonyl) amino) cyclobutane-1-carboxylic acid was used as the starting material instead of 1- (tert-butoxycarbonyl) amino) cyclohexane-1-carboxylic acid. The product was a white solid in 76.4% yield.
Preparation of 21-amino-N-phenylcyclobutane-1-carboxamide
Figure BDA0003352346640000201
The synthesis of the target compound was similar to 1.2, except that the starting material was tert-butyl (1- (phenylcarbamoyl) cyclobutyl) carbamate instead of tert-butyl (1- (phenylcarbamoyl) cyclohexyl) carbamate. The product was a yellow oily liquid with a yield of 98.1%. The reaction is directly carried out without further treatment.
Preparation of 33-bromo-1- (3-chloropyridin-2-yl) -N- (1- (phenylcarbamoyl) cyclobutyl) -1H-pyrazole-5-carboxamide
Figure BDA0003352346640000202
The synthesis of the target compound was similar to 1.4, except that 1-amino-N-phenylcyclopentane-1-carboxamide was used as the starting material instead of 1-amino-N-phenylcyclohexane-1-carboxamide. The product was a white solid in 78.7% yield.
1H NMR(400MHz,DMSO-d6)δ9.34(s,1H),9.17(s,1H),8.41(dd,J＝4.7,1.5Hz,1H),8.13(dd,J＝8.0,1.5Hz,1H),7.58(dd,J＝8.0,4.7Hz,1H),7.51(d,J＝7.9Hz,2H),7.44(s,1H),7.28(t,J＝7.7Hz,2H),7.03(t,J＝7.3Hz,1H),2.66–2.54(m,2H),2.28–2.16(m,2H),1.98–1.77(m,2H).
Example 4: preparation of 3-bromo-1- (3-chloropyridin-2-yl) -N- (1- (phenylcarbamoyl) -2-vinylcyclopropyl) -1H-pyrazole-5-carboxamide (Compound I-9)
4.1 preparation of tert-butyl (1- (phenylcarbamoyl) -2-vinylcyclopropyl) carbamate
Figure BDA0003352346640000203
The synthesis of the target compound was similar to 1.1, except that the starting material was 1- ((tert-butoxycarbonyl) amino) -2-vinylcyclopropane-1-carboxylic acid, instead of 1- (tert-butoxycarbonyl) amino) cyclohexane-1-carboxylic acid. The product was a white solid in 78.5% yield.
Preparation of 21-amino-N-phenyl-2-vinylcyclopropane-1-carboxamide
Figure BDA0003352346640000204
The synthesis of the target compound was similar to 1.2, except that the starting material was tert-butyl (1- (phenylcarbamoyl) -2-vinylcyclopropyl) carbamate instead of tert-butyl (1- (phenylcarbamoyl) cyclohexyl) carbamate. The product was a yellow oily liquid with a yield of 98.4%. The reaction is directly carried out without further treatment.
Preparation of 33-bromo-1- (3-chloropyridin-2-yl) -N- (1- (phenylcarbamoyl) -2-vinylcyclopropyl) -1H-pyrazole-5-carboxamide
The synthesis of the target compound was similar to 1.4, except that 1-amino-N-phenylcyclopentane-1-carboxamide was used as the starting material instead of 1-amino-N-phenylcyclohexane-1-carboxamide. The product was a white solid in 77.3% yield.
1H NMR(400MHz,DMSO-d6)δ9.60(s,1H),9.34(s,1H),8.47(dd,J＝4.7,1.4Hz,1H),8.18(dd,J＝8.1,1.4Hz,1H),7.62(dd,J＝8.1,4.7Hz,1H),7.50(d,J＝7.7Hz,2H),7.38(s,1H),7.29(t,J＝7.9Hz,2H),7.06(t,J＝7.4Hz,1H),5.62(dt,J＝17.2,9.8Hz,1H),5.26(dd,J＝17.2,1.6Hz,1H),5.06(dd,J＝10.3,1.6Hz,1H),2.31(dd,J＝17.2,9.1Hz,1H),1.81(dd,J＝7.5,5.2Hz,1H),1.25–1.17(m,1H).
Example 5: preparation of 3-bromo-1- (3-chloropyridin-2-yl) -N- (2-phenyl-1- (phenylcarbamoyl) cyclopropyl) -1H-pyrazole-5-carboxamide (Compound I-13)
Preparation of ethyl 11-amino-2-phenylcyclopropane-1-carboxylate
Figure BDA0003352346640000211
2.35g (10mmol) of ethyl 1-nitro-2-phenylcyclopropane-1-carboxylate, 60mL of ethanol, 20mL of 1N diluted hydrochloric acid, and 3.20g (50mmol) of zinc powder were put in this order in a 250mL three-necked flask. After 12h reaction at room temperature, 100mL of saturated aqueous sodium bicarbonate solution was added. The organic phase is separated off by filtration through Celite and the aqueous phase is extracted twice with 100mL of dichloromethane. The combined organic phases were dried over anhydrous sodium sulfate and the solvent was removed by rotary evaporation to give 1.95g of crude product as a yellow oil in 95.1% yield. The reaction is directly carried out without further treatment.
Preparation of ethyl 21- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylate
Figure BDA0003352346640000221
1.95g (9.5mmol) of ethyl 1-amino-2-phenylcyclopropane-1-carboxylate, 80mL of dichloromethane, 3.03g (30mmol) of triethylamine and a 250mL three-necked flask were placed in this order, and a solution (50mL) of 3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carbonyl chloride (3.65g, 10mmol) in dichloromethane was added dropwise over an ice bath. After 4h reaction at room temperature, 100mL of water was added. The organic phase is separated off and the aqueous phase is extracted twice with 50mL of dichloromethane. The combined organic phases were dried over anhydrous sodium sulfate, the solvent was removed by rotary evaporation and the crude product was purified by column chromatography to give 2.61g of product in 56.1% yield.
Preparation of 31- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid
Figure BDA0003352346640000222
2.61g (4.9mmol) of ethyl 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylate, 80mL of ethanol, 20mL of water, and 0.2g (5.4mmol) of sodium hydroxide were successively placed in a 250mL three-necked flask. After 2h reaction at 50 ℃ the solvent was removed by rotary evaporation and 80mL of ethyl acetate and 80mL of a saturated aqueous solution of citric acid were added. The organic phase is separated off and the aqueous phase is extracted twice with 50mL of ethyl acetate. The combined organic phases were dried over anhydrous sodium sulfate and the solvent was removed by rotary evaporation to give 2.23g of crude white solid in 98.6% yield. The reaction is directly carried out without further treatment.
Preparation of 43-bromo-1- (3-chloropyridin-2-yl) -N- (2-phenyl-1- (phenylcarbamoyl) cyclopropyl) -1H-pyrazole-5-carboxamide
Figure BDA0003352346640000223
2.42g (4.8mmol) of 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid, 80mL of acetonitrile, 4.18g (4.5mmol) of aniline, 1.24g (15mmol) of N-methylpyrrole, 1.51g (5.4mmol) of tetramethylchlorourea hexafluorophosphate were charged in that order into a 250mL three-necked flask. After 8h reaction at room temperature, the solvent was removed by rotary evaporation and 80mL of ethyl acetate and 80mL of a saturated aqueous solution of citric acid were added. The organic phase is separated off and the aqueous phase is extracted twice with 50mL of ethyl acetate. The combined organic phases were dried over anhydrous sodium sulfate, the solvent was removed by rotary evaporation and the crude product was purified by column chromatography to give the product as a white solid 1.22g with a yield of 47.3%.
1H NMR(400MHz,DMSO-d6)δ9.52(s,1H),9.46(s,1H),8.48(dd,J＝4.7,1.5Hz,1H),8.20(dd,J＝8.1,1.5Hz,1H),7.64(dd,J＝8.1,4.7Hz,1H),7.40(s,1H),7.31–7.11(m,9H),7.00–6.95(m,1H),2.87(t,J＝9.0Hz,1H),2.24(dd,J＝8.3,5.5Hz,1H),1.35(dd,J＝9.7,5.5Hz,1H).
Compounds I-14, I-17, I-19 to I-42 were synthesized as described in example 5, and the corresponding NMR data are shown in Table II.
Example 6: preparation of N- (1- (benzylcarbamoyl) -2- (4-chlorophenyl) cyclopropyl) -3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide (Compound I-15)
Preparation of 6.11-amino-2- (4-chlorophenyl) cyclopropane-1-carboxylic acid ethyl ester
Figure BDA0003352346640000231
The synthesis of the target compound is similar to that of 5.1, except that the raw material is 2- (4-chlorophenyl) -1-nitrocyclopropane-1-carboxylic acid ethyl ester instead of 1-nitro-2-phenylcyclopropane-1-carboxylic acid ethyl ester. The product was a yellow oily liquid with a yield of 97.6%.
Preparation of ethyl 21- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2- (4-chlorophenyl) cyclopropane-1-carboxylate
Figure BDA0003352346640000232
The synthesis of the target compound was similar to 5.2, except that the starting material was ethyl 1-amino-2- (4-chlorophenyl) cyclopropane-1-carboxylate instead of ethyl 1-amino-2-phenylcyclopropane-1-carboxylate. The product was a white solid in 56.1% yield.
Preparation of 31- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2- (4-chlorophenyl) cyclopropane-1-carboxylic acid
Figure BDA0003352346640000241
The synthesis of the target compound was similar to 5.3, except that the starting material was ethyl 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2- (4-chlorophenyl) cyclopropane-1-carboxylate instead of ethyl 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylate. The product was a white solid in 92.7% yield.
Preparation of 4N- (1- (benzylcarbamoyl) -2- (4-chlorophenyl) cyclopropyl) -3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide
Figure BDA0003352346640000242
The synthesis of the target compound was similar to 5.4, except that benzylamine and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2- (4-chlorophenyl) cyclopropane-1-carboxylic acid were used as starting materials instead of aniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid. The product was a white solid in 66.9% yield.
1H NMR(400MHz,DMSO-d6)δ9.50(s,1H),8.60(t,J＝5.9Hz,1H),8.48(dd,J＝4.7,1.5Hz,1H),8.20(dd,J＝8.1,1.5Hz,1H),7.64(dd,J＝8.1,4.7Hz,1H),7.44–7.37(m,3H),7.33–7.13(m,7H),4.37–4.17(m,2H),2.90–2.82(m,1H),2.29–2.20(m,1H),1.38–1.31(m,1H).
Example 7: preparation of N- (1- (acetylamino-formyl) -2- (4-chlorophenyl) cyclopropyl) -3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide (Compound I-16)
Preparation of 13-bromo-N- (1-carbamoyl-2- (4-chlorophenyl) cyclopropyl) -1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide
Figure BDA0003352346640000243
The synthesis of the target compound was similar to 5.4, except that ammonia and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2- (4-chlorophenyl) cyclopropane-1-carboxylic acid were used as starting materials instead of aniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid. The product was a white solid in 55.3% yield.
Preparation of 2N- (1- (acetylamino-formyl) -2- (4-chlorophenyl) cyclopropyl) -3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide
Figure BDA0003352346640000251
1.48g (3.0mmol) of 3-bromo-N- (1-carbamoyl-2- (4-chlorophenyl) cyclopropyl) -1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide, 50mL of methylene chloride, and 1.10g (9.0mmol) of 4-dimethylaminopyridine were sequentially placed in a 250mL three-necked flask. A solution of acetyl chloride (0.27g, 3.5mmol) in dichloromethane (6mL) was added dropwise under ice bath. After 8h reaction at 35 ℃ 80mL of water were added. The organic phase is separated off and the aqueous phase is extracted twice with 50mL of dichloromethane. The combined organic phases were dried over anhydrous sodium sulfate, the solvent was removed by rotary evaporation and the crude product was purified by column chromatography to give 1.14g of a white solid with a yield of 70.7%.
1H NMR(400MHz,DMSO-d6)δ8.72(s,1H),8.49(dd,J＝4.7,1.5Hz,1H),8.24(dd,J＝8.1,1.5Hz,1H),7.63(dd,J＝8.1,4.7Hz,1H),7.51(s,1H),7.37–7.29(m,3H),7.23–7.18(m,2H),3.40–3.35(m,1H),2.21–2.17(m,1H),2.14(s,3H),2.00–1.96(m,1H).
Example 8: preparation of 3-bromo-N- (2- (4-chlorophenyl) -1- (dimethylcarbamoyl) cyclopropyl) -1- (3-chloropyridin-2-yl) -N-methyl-1H-pyrazole-5-carboxamide (Compound I-18)
Preparation of 13-bromo-N- (2- (4-chlorophenyl) -1- (dimethylcarbamoyl) cyclopropyl) -1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide
Figure BDA0003352346640000252
The synthesis of the target compound was similar to 5.4, except that dimethylamine and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2- (4-chlorophenyl) cyclopropane-1-carboxylic acid were used as starting materials instead of aniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid. The product was a white solid in 78.5% yield.
Preparation of 23-bromo-N- (2- (4-chlorophenyl) -1- (dimethylcarbamoyl) cyclopropyl) -1- (3-chloropyridin-2-yl) -N-methyl-1H-pyrazole-5-carboxamide
Figure BDA0003352346640000261
1.31g (2.5mmol) of 3-bromo-N- (2- (4-chlorophenyl) -1- (dimethylcarbamoyl) cyclopropyl) -1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide, 20mL of N, N-dimethylformamide and 0.41g (3.0mmol) of potassium carbonate were successively placed in a 150mL three-necked flask. A further 0.40g (2.8mmol) of methyl iodide were added. After 6h reaction at 35 ℃ 40mL of water and 40mL of dichloromethane were added. The organic phase is separated off and the aqueous phase is extracted twice with 20mL of dichloromethane. The combined organic phases were dried over anhydrous sodium sulfate, the solvent was removed by rotary evaporation and the crude product was purified by column chromatography to give 1.21g of a white solid with a yield of 90.1%.
1H NMR(400MHz,DMSO-d6)δ8.47(dd,J＝4.7,1.5Hz,1H),8.20(dd,J＝8.1,1.5Hz,1H),7.59(dd,J＝8.1,4.7Hz,1H),7.35–7.27(m,3H),7.22–7.15(m,2H),3.42–3.37(m,1H),3.12(s,3H),3.01(s,6H),2.23–2.18(m,1H),2.01–1.95(m,1H).
Example 9: preparation of 3-bromo-1- (3-chloropyridin-2-yl) -N- (1- (phenylcarbamoyl) -2- (thiophen-3-yl) cyclopropyl) -1H-pyrazole-5-carboxamide (Compound I-40)
Preparation of 9.11-amino-2- (thien-3-yl) cyclopropane-1-carboxylic acid ethyl ester
Figure BDA0003352346640000262
The synthesis of the target compound was similar to 5.1, except that the starting material was 1-nitro-2- (thiophen-3-yl) cyclopropane-1-carboxylic acid ethyl ester instead of 1-nitro-2-phenylcyclopropane-1-carboxylic acid ethyl ester. The product was a yellow oily liquid in 93.3% yield.
9.21 preparation of ethyl 3- (bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2- (thien-3-yl) cyclopropane-1-carboxylate
Figure BDA0003352346640000263
The synthesis of the target compound was similar to 5.2, except that the starting material was ethyl 1-amino-2- (thiophen-3-yl) cyclopropane-1-carboxylate instead of ethyl 1-amino-2-phenylcyclopropane-1-carboxylate. The product was a white solid in 48.5% yield.
9.9 preparation of 31- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2- (thien-3-yl) cyclopropane-1-carboxylic acid
Figure BDA0003352346640000271
The synthesis of the target compound was similar to 5.3, except that the starting material was ethyl 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide) -2- (thiophen-3-yl) cyclopropane-1-carboxylate instead of ethyl 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide) -2-phenylcyclopropane-1-carboxylate. The product was a white solid in 91.4% yield.
9.43-bromo-1- (3-chloropyridin-2-yl) -N- (1- (phenylcarbamoyl) -2- (thien-3-yl) cyclopropyl) -1H-pyrazole-5-carboxamide preparation
Figure BDA0003352346640000272
The synthesis of the target compound was similar to 5.4, except that 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide) -2- (thiophen-3-yl) cyclopropane-1-carboxylic acid was used as starting material instead of 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide) -2-phenylcyclopropane-1-carboxylic acid. The product was a white solid in 63.6% yield.
1H NMR(400MHz,DMSO-d6)δ9.59(s,1H),9.51(s,1H),8.47(dd,J＝4.7,1.5Hz,1H),8.18(dd,J＝8.1,1.5Hz,1H),7.62(dd,J＝8.1,4.7Hz,1H),7.46–7.38(m,2H),7.30(s,1H),7.21–7.09(m,3H),7.04(t,J＝7.4Hz,1H),6.99(s,1H),6.95(d,J＝5.4Hz,1H),2.97–2.89(m,1H),2.22–2.16(m,1H),1.36–1.27(m,1H).
Example 10: preparation of 3-bromo-1- (3-chloropyridin-2-yl) -N- (2, 3-diphenyl-1- (phenylcarbamoyl) cyclopropyl) -1H-pyrazole-5-carboxamide (Compound I-43)
10.1 preparation of ethyl 11-amino-2, 3-diphenylcyclopropane-1-carboxylate
Figure BDA0003352346640000281
The synthesis of the target compound is similar to 5.1, except that the raw material is 1-nitro-2, 3-diphenyl cyclopropane-1-carboxylic acid ethyl ester instead of 1-nitro-2-phenyl cyclopropane-1-carboxylic acid ethyl ester. The product was a yellow oily liquid in 93.4% yield.
10.21 preparation of ethyl 3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2, 3-diphenylcyclopropane-1-carboxylate
Figure BDA0003352346640000282
The synthesis of the target compound was similar to 5.2, except that ethyl 1-amino-2, 3-diphenylcyclopropane-1-carboxylate was used as the starting material instead of ethyl 1-amino-2-phenylcyclopropane-1-carboxylate. The product was a white solid in 55.7% yield.
10.1 preparation of 31- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2, 3-diphenylcyclopropane-1-carboxylic acid
Figure BDA0003352346640000283
The synthesis of the target compound was similar to 5.3, except that the starting material was ethyl 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide) -2, 3-diphenylcyclopropane-1-carboxylate instead of ethyl 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide) -2-phenylcyclopropane-1-carboxylate. The product was a white solid in 93.4% yield.
Preparation of 43-bromo-1- (3-chloropyridin-2-yl) -N- (2, 3-diphenyl-1- (phenylcarbamoyl) cyclopropyl) -1H-pyrazole-5-carboxamide
Figure BDA0003352346640000284
The synthesis of the target compound was similar to 5.4, except that 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2, 3-diphenylcyclopropane-1-carboxylic acid was used as the starting material instead of 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid. The product was a white solid in 54.3% yield.
1H NMR(400MHz,DMSO-d6)δ9.60(s,1H),9.43(s,1H),8.45(dd,J＝4.7,1.5Hz,1H),8.14(dd,J＝8.1,1.5Hz,1H),7.60(dd,J＝8.1,4.7Hz,1H),7.44–7.35(m,2H),7.32–7.05(m,13H),7.03(t,J＝7.4Hz,1H),3.17–3.10(m,2H).
Example 11: preparation of 3-bromo-1- (3-chloropyridin-2-yl) -N- (1-carbamoylcyclopropyl) -1H-pyrazole-5-carboxamide (Compound I-44)
11.1 preparation of ethyl 11- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carboxylate
Figure BDA0003352346640000291
The synthesis of the target compound was similar to 5.2, except that the starting material was ethyl 1-aminocyclopropane-1-carboxylate hydrochloride instead of ethyl 1-amino-2-phenylcyclopropane-1-carboxylate. The product was a white solid in 82.7% yield.
11.21 preparation of- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carboxylic acid
Figure BDA0003352346640000292
The synthesis of the target compound was similar to 5.3, except that the starting material was ethyl 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carboxylate instead of ethyl 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylate. The product was a white solid in 95.2% yield.
Preparation of 33-bromo-1- (3-chloropyridin-2-yl) -N- (1-carbamoylcyclopropyl) -1H-pyrazole-5-carboxamide
Figure BDA0003352346640000293
The synthesis of the target compound was similar to 5.4, except that ammonia and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carboxylic acid were used as starting materials in place of aniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid. The product was a white solid in 55.8% yield.
1H NMR(400MHz,DMSO-d6)δ9.63(s,1H),8.47(dd,J＝4.7,1.5Hz,1H),8.16(dd,J＝8.1,1.5Hz,1H),7.64(s,2H),7.59(dd,J＝8.1,4.7Hz,1H),7.32(s,1H),1.44–1.39(m,2H),1.06–1.00(m,2H).
Compounds I-45, I-47, I-53 to I-55, I-60, I-61, I-63, I-64, I-66, I-67, I-70, I-72, I-76 to I-79, I-82 to I-92, I-94 to I-96, I-98 to I-100, I-102 to I-104, I-107 to I-112, I-114, I-115 were each synthesized according to the method of example 11, with the corresponding NMR charts shown in Table II.
Example 12: preparation of 3-bromo-1- (3-bromopyridin-2-yl) -N- (1- (ethylcarbamoyl) cyclopropyl) -1H-pyrazole-5-carboxamide (Compound I-46)
Figure BDA0003352346640000301
The synthesis of the title compound was similar to 5.4, except that the starting material was ethylamine in tetrahydrofuran and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carboxylic acid instead of aniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid. The product was a white solid in 83.2% yield.
1H NMR(400MHz,DMSO-d6)δ9.59(s,1H),8.55(t,J＝5.3Hz,1H),8.46(dd,J＝4.7,1.5Hz,1H),8.19(dd,J＝8.1,1.5Hz,1H),7.60(dd,J＝8.1,4.7Hz,1H),7.30(s,1H),3.12–2.99(m,2H),1.48–1.40(m,2H),1.07–1.00(m,2H),0.98(t,J＝7.2Hz,3H).
Example 13: preparation of 3-bromo-1- (3-chloropyridin-2-yl) -N- (1- (2-methylallyl) carbamoyl) cyclopropyl) -1H-pyrazole-5-carboxamide (Compound I-48)
Figure BDA0003352346640000302
The synthesis of the title compound was similar to 5.4, except that 2-methylallylamine and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carboxylic acid were used as starting materials instead of aniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid. The product was a white solid in 78.4% yield.
1H NMR(400MHz,DMSO-d6)δ9.55(s,1H),8.47(dd,J＝4.7,1.5Hz,1H),8.30(t,J＝5.7Hz,1H),8.20(dd,J＝8.1,1.5Hz,1H),7.62(dd,J＝8.1,4.7Hz,1H),7.32(s,1H),4.76(d,J＝34.8Hz,2H),3.61(d,J＝5.7Hz,2H),3.12–2.99(m,2H),1.63(s,3H),1.44–1.38(m,2H),1.05–0.95(m,2H).
Example 14: preparation of 3-bromo-1- (3-chloropyridin-2-yl) -N- (1- (prop-2-yn-1-ylcarbamoyl) cyclopropyl) -1H-pyrazole-5-carboxamide (Compound I-49)
Figure BDA0003352346640000311
The synthesis of the target compound was similar to 5.4, except that propargylamine and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carboxylic acid were used as starting materials in place of aniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid. The product was a white solid in 74.3% yield.
1H NMR(400MHz,DMSO-d6)δ9.53(s,1H),8.64(t,J＝5.4Hz,1H),8.47(dd,J＝4.7,1.5Hz,1H),8.21(dd,J＝8.1,1.5Hz,1H),7.64(dd,J＝8.1,4.7Hz,1H),7.28(s,1H),3.85(dd,J＝5.6,2.5Hz,2H),3.09(t,J＝2.5Hz,1H),1.38–
1.30(m,2H),1.11–1.03(m,2H).
Example 15: preparation of 3-bromo-1- (3-chloropyridin-2-yl) -N- (1- (cyclopropylcarbamoyl) cyclopropyl) -1H-pyrazole-5-carboxamide (Compound I-50)
Figure BDA0003352346640000312
The synthesis of the title compound was similar to 5.4, except that cyclopropane-1-carboxylic acid was used as the starting material in place of aniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid, as compared to 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carboxylic acid. The product was a white solid in 78.7% yield.
1H NMR(400MHz,DMSO-d6)δ9.57(s,1H),8.49(dd,J＝4.7,1.5Hz,1H),8.37(d,J＝3.9Hz,1H),8.20(dd,J＝8.1,1.5Hz,1H),7.61(dd,J＝8.1,4.7Hz,1H),7.26(s,1H),2.60–2.51(m,1H),1.44–1.38(m,2H),1.12–1.03(m,2H),0.61–0.52(m,2H),0.45–0.32(m,2H).
Example 16: preparation of 3-bromo-1- (3-chloropyridin-2-yl) -N- (1- ((oxetan-3-ylmethyl) carbamoyl) cyclopropyl) -1H-pyrazole-5-carboxamide (Compound I-51)
Figure BDA0003352346640000321
The synthesis of the title compound was similar to 5.4, except that 3-aminomethyloxetane and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carboxylic acid were used as starting materials instead of aniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid. The product was a white solid in 55.6% yield.
1H NMR(400MHz,DMSO-d6)δ9.60(s,1H),8.62(t,J＝5.4Hz,1H),8.46(dd,J＝4.7,1.5Hz,1H),8.17(dd,J＝8.1,1.5Hz,1H),7.59(dd,J＝8.1,4.7Hz,1H),7.30(s,1H),4.28–4.17(m,2H),3.60–3.42(m,4H),2.64–2.56(m,1H),1.43–1.38(m,2H),1.14–1.05(m,2H).
Example 17: preparation of 3-bromo-1- (3-chloropyridin-2-yl) -N- (1- (phenylcarbamoyl) cyclopropyl) -1H-pyrazole-5-carboxamide (Compound I-52)
Figure BDA0003352346640000322
The synthesis of the target compound was similar to 5.4, except that 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carboxylic acid was used as the starting material instead of 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid. The product was a white solid in 68.4% yield.
1H NMR(400MHz,DMSO-d6)δ9.50(s,1H),9.29(s,1H),8.47(dd,J＝4.7,1.5Hz,1H),8.23(dd,J＝8.1,1.5Hz,1H),7.61(dd,J＝8.1,4.7Hz,1H),7.54–7.49(m,2H),7.36(s,1H),7.32–7.26(m,2H),7.06(t,J＝7.4Hz,1H),1.45–1.39(m,2H),1.06–1.00(m,2H).
Example 18: preparation of 3-bromo-N- (1- ((4-chlorophenyl) carbamoyl) cyclopropyl) -1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide (Compound I-56)
Figure BDA0003352346640000331
The synthesis of the target compound was similar to 5.4, except that 4-chloroaniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carboxylic acid were used as starting materials in place of aniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid. The product was a white solid in 72.3% yield.
1H NMR(400MHz,DMSO-d6)δ9.74(s,1H),9.37(s,1H),8.48(dd,J＝4.8,1.5Hz,1H),8.17(dd,J＝8.0,1.5Hz,1H),7.64–7.57(m,3H),7.45(s,1H),7.35(d,J＝8.8Hz,2H),1.44–1.38(m,2H),1.07–1.02(m,2H).
Example 19: preparation of 3-bromo-N- (1- ((3-chlorophenyl) carbamoyl) cyclopropyl) -1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide (Compound I-57)
Figure BDA0003352346640000332
The synthesis of the target compound was similar to 5.4, except that 3-chloroaniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carboxylic acid were used as starting materials in place of aniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid. The product was a white solid in 72.3% yield.
1H NMR(400MHz,DMSO-d6)δ9.52(s,1H),9.20(s,1H),8.48(dd,J＝4.7,1.5Hz,1H),8.19(dd,J＝8.1,1.5Hz,1H),7.76(dd,J＝8.0,1.6Hz,1H),7.63(dd,J＝8.1,4.7Hz,1H),7.49(dd,J＝8.0,1.5Hz,1H),7.36–7.29(m,2H),7.18(dd,J＝8.1,1.6Hz,1H),1.44(q,J＝4.4Hz,2H),1.09(q,J＝4.4Hz,2H).
Example 20: preparation of 3-bromo-N- (1- ((2-chlorophenyl) carbamoyl) cyclopropyl) -1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide (Compound I-58)
Figure BDA0003352346640000333
The synthesis of the target compound was similar to 5.4, except that 2-chloroaniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carboxylic acid were used as starting materials in place of aniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid. The product was a white solid in 62.7% yield.
1H NMR(400MHz,DMSO-d6)δ9.68(s,1H),9.24(s,1H),8.48(dd,J＝4.7,1.5Hz,1H),8.18(dd,J＝8.1,1.5Hz,1H),7.72–7.68(m,1H),7.62(dd,J＝8.1,4.7Hz,1H),7.53(dd,J＝8.0,1.2Hz,1H),7.36(s,1H),7.33(t,J＝8.1Hz,1H),7.12(dd,J＝8.0,1.2Hz,1H),1.44(dd,J＝7.6,4.4Hz,2H),1.05(dd,J＝7.6,4.4Hz,2H).
Example 21: preparation of 3-bromo-N- (1- ((4-methoxyphenyl) carbamoyl) cyclopropyl) -1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide (Compound I-59)
Figure BDA0003352346640000341
The synthesis of the target compound was similar to 5.4, except that 4-methoxyaniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carboxylic acid were used as starting materials instead of aniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid. The product was a white solid in 76.6% yield.
1H NMR(400MHz,DMSO-d6)δ9.43(s,1H),9.23(s,1H),8.49(dd,J＝4.7,1.5Hz,1H),8.18(dd,J＝8.1,1.5Hz,1H),7.62(dd,J＝8.1,4.7Hz,1H),7.43–7.37(m,2H),7.35(s,1H),6.90–6.84(m,2H),3.71(s,3H),1.43–1.36(m,2H),1.03–0.96(m,2H).
Example 22: preparation of 3-bromo-N- (1- ((4-cyanophenyl) carbamoyl) cyclopropyl) -1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide (Compound I-62)
Figure BDA0003352346640000342
The synthesis of the target compound was similar to 5.4, except that 4-cyanoaniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carboxylic acid were used as starting materials in place of aniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid. The product was a white solid in 70.5% yield.
1H NMR(400MHz,DMSO-d6)δ9.92(s,1H),9.27(s,1H),8.47(dd,J＝4.7,1.5Hz,1H),8.17(dd,J＝8.1,1.5Hz,1H),7.82–7.74(m,3H),7.61(dd,J＝8.1,4.7Hz,1H),7.38(s,1H),1.49–1.43(m,2H),1.12–1.06(m,2H).
Example 23: preparation of 3-bromo-N- (1- ((4-fluorophenyl) carbamoyl) cyclopropyl) -1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide (Compound I-65)
Figure BDA0003352346640000351
The synthesis of the target compound was similar to 5.4, except that 4-fluoroaniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carboxylic acid were used as starting materials in place of aniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid. The product was a white solid in 73.2% yield.
1H NMR(400MHz,DMSO-d6)δ9.52(s,1H),9.36(s,1H),8.50(dd,J＝4.7,1.5Hz,1H),8.20(dd,J＝8.1,1.5Hz,1H),7.62(dd,J＝8.1,4.7Hz,1H),7.32(s,1H),7.28–7.20(m,2H),6.97(t,J＝8.0,2H),1.42–1.36(m,2H),1.05–0.95(m,2H).
Example 24: preparation of 3-bromo-N- (1- ((4-trifluoromethylphenyl) carbamoyl) cyclopropyl) -1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide (Compound I-68)
Figure BDA0003352346640000352
The synthesis of the target compound was similar to 5.4, except that 4-trifluoromethylaniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carboxylic acid were used as starting materials instead of aniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid. The product was a white solid in 69.6% yield.
1H NMR(400MHz,DMSO-d6)δ9.60(s,1H),9.33(s,1H),8.52(dd,J＝4.7,1.5Hz,1H),8.20(dd,J＝8.1,1.5Hz,1H),7.77(d,J＝8.6,2H),7.63(dd,J＝8.1,4.7Hz,1H),7.47(d,J＝8.6,2H),7.30(s,1H),1.48–1.42(m,2H),1.15–1.03(m,2H).
Example 25: preparation of 3-bromo-N- (1- ((4-tert-butylphenyl) carbamoyl) cyclopropyl) -1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide (Compound I-69)
Figure BDA0003352346640000361
The synthesis of the target compound was similar to 5.4, except that 4-tert-butylaniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carboxylic acid were used as starting materials instead of aniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid. The product was a white solid in 73.9% yield.
1H NMR(400MHz,DMSO-d6)δ9.53(s,1H),9.10(s,1H),8.43(dd,J＝4.7,1.5Hz,1H),8.15(dd,J＝8.1,1.5Hz,1H),7.58(dd,J＝8.1,4.7Hz,1H),7.28(s,1H),7.23(d,J＝8.4,2H),7.16(d,J＝8.4,2H),1.43–1.30(m,2H),1.22(s,9H),1.09–1.00(m,2H).
Example 26: preparation of 3-bromo-N- (1- ((4-vinylphenyl) carbamoyl) cyclopropyl) -1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide (Compound I-71)
Figure BDA0003352346640000362
The synthesis of the target compound was similar to 5.4, except that 4-vinylaniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carboxylic acid were used as starting materials in place of aniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid. The product was a white solid in 69.3% yield.
1H NMR(400MHz,DMSO-d6)δ9.53(s,1H),9.14(s,1H),8.45(dd,J＝4.7,1.5Hz,1H),8.18(dd,J＝8.1,1.5Hz,1H),7.60(dd,J＝8.1,4.7Hz,1H),7.31–7.18(m,3H),7.13(d,J＝8.0,2H),6.78–6.67(m,1H),6.64–6.58(m,1H),5.56–5.47(m,1H),1.44–1.32(m,2H),1.10–1.03(m,2H).
Example 27: preparation of 3-bromo-N- (1- ((4-phenylphenyl) carbamoyl) cyclopropyl) -1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide (Compound I-73)
Figure BDA0003352346640000363
The synthesis of the target compound was similar to 5.4, except that 4-phenylaniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carboxylic acid were used as starting materials in place of aniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid. The product was a white solid in 72.6% yield.
1H NMR(400MHz,DMSO-d6)δ9.58(s,1H),9.32(s,1H),8.47(dd,J＝4.7,1.5Hz,1H),8.20(dd,J＝8.1,1.5Hz,1H),7.63–7.57(m,3H),7.54–7.49(m,2H),7.47–7.41(m,2H),7.37–7.30(m,3H),1.43–1.30(m,2H),1.14–1.06(m,2H).
Example 28: preparation of 3-bromo-1- (3-chloropyridin-2-yl) -N- (1- ((4- (furan-2-yl) phenyl) carbamoyl) cyclopropyl) -1H-pyrazole-5-carboxamide (Compound I-74)
Figure BDA0003352346640000371
The synthesis of the target compound was similar to 5.4, except that 4-methoxyaniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carboxylic acid were used as starting materials instead of aniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid. The product was a white solid in 54.2% yield.
1H NMR(400MHz,DMSO-d6)δ9.60(s,1H),9.28(s,1H),8.47(dd,J＝4.7,1.5Hz,1H),8.21(dd,J＝8.1,1.5Hz,1H),7.70–7.60(m,3H),7.57–7.47(m,3H),7.03–6.98(m,1H),6.70–6.57(m,1H),1.44–1.32(m,2H),1.16–1.07(m,2H).
Example 29: preparation of 3-bromo-N- (1- ((4-methylthiophenyl) carbamoyl) cyclopropyl) -1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide (Compound I-75)
Figure BDA0003352346640000372
The synthesis of the title compound was similar to 5.4, except that 4-methylthioaniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carboxylic acid were used as starting materials in place of aniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid. The product was a white solid in 77.8% yield.
1H NMR(400MHz,DMSO-d6)δ9.59(s,1H),8.82(s,1H),8.43(dd,J＝4.7,1.5Hz,1H),8.15(dd,J＝8.1,1.5Hz,1H),7.57(dd,J＝8.1,4.7Hz,1H),7.27(s,1H),7.20(d,J＝8.4,2H),6.82(d,J＝8.4,2H),3.43(s,3H),1.39–1.30(m,2H),1.06–0.97(m,2H).
Example 30: preparation of 3-bromo-N- (1- ((2-bromo-3-methylphenyl) carbamoyl) cyclopropyl) -1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide (Compound I-80)
Figure BDA0003352346640000381
The synthesis of the target compound was similar to 5.4, except that the starting materials were 2-bromo-3-methylaniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carboxylic acid instead of aniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid. The product was a white solid in 69.3% yield.
1H NMR(400MHz,DMSO-d6)δ9.60(s,1H),9.51(s,1H),8.48(dd,J＝4.7,1.5Hz,1H),8.20(dd,J＝8.1,1.5Hz,1H),7.65–7.60(m,2H),7.30–7.22(m,2H),7.07(d,J＝7.8,1H),2.41(s,3H),1.49–1.41(m,2H),1.16–1.07(m,2H).
Example 31: preparation of 3-bromo-N- (1- ((2, 4-dichlorophenyl) carbamoyl) cyclopropyl) -1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide (Compound I-81)
Figure BDA0003352346640000382
The synthesis of the target compound was similar to 5.4, except that 2, 4-dichloroaniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carboxylic acid were used as starting materials instead of aniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid. The product was a white solid in 65.5% yield.
1H NMR(400MHz,DMSO-d6)δ9.51(s,1H),9.29(s,1H),8.49(dd,J＝4.7,1.5Hz,1H),8.20(dd,J＝8.1,1.5Hz,1H),7.72(d,J＝8.8Hz,1H),7.67(d,J＝2.4Hz,1H),7.64(dd,J＝8.1,4.7Hz,1H),7.42(dd,J＝8.8,2.4Hz,1H),7.34(s,1H),1.49–1.40(m,2H),1.13–1.06(m,2H).
Example 32: preparation of 3-bromo-N- (1- ((3,4, 5-trichlorophenyl) carbamoyl) cyclopropyl) -1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide (Compound I-93)
Figure BDA0003352346640000391
The synthesis of the target compound was similar to 5.4, except that 3,4, 5-trichloroaniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carboxylic acid were used as starting materials instead of aniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid. The product was a white solid in 61.7% yield.
1H NMR(400MHz,DMSO-d6)δ9.90(s,1H),9.30(s,1H),8.48(dd,J＝4.7,1.6Hz,1H),8.18(dd,J＝8.1,1.6Hz,1H),7.94(s,2H),7.62(dd,J＝8.1,4.7Hz,1H),7.36(s,1H),1.46(q,J＝4.5Hz,2H),1.08(q,J＝4.5Hz,2H).
Example 33: preparation of 3-bromo-1- (3-chloropyridin-2-yl) -N- (1- (thien-2-ylcarbamoyl) cyclopropyl) -1H-pyrazole-5-carboxamide (Compound I-97)
Figure BDA0003352346640000392
The synthesis of the target compound was similar to 5.4, except that 2-aminothiophene and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carboxylic acid were used as starting materials instead of aniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid. The product was a white solid in 66.1% yield.
1H NMR(400MHz,DMSO-d6)δ9.58(s,1H),9.20(s,1H),8.47(dd,J＝4.7,1.5Hz,1H),8.23(dd,J＝8.1,1.5Hz,1H),7.61(dd,J＝8.1,4.7Hz,1H),7.39–7.27(m,3H),7.18(t,J＝7.2Hz,1H),1.44–1.38(m,2H),1.15–1.05(m,2H).
Example 34: preparation of 3-bromo-1- (3-chloropyridin-2-yl) -N- (1- (((6-chloropyridin-3-yl) methyl) carbamoyl) cyclopropyl) -1H-pyrazole-5-carboxamide (Compound I-101)
Figure BDA0003352346640000393
The synthesis of the target compound was similar to 5.4, except that 6-chloropyridylmethylamine and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carboxylic acid were used as starting materials instead of aniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid. The product was a white solid in 76.3% yield.
1H NMR(400MHz,DMSO-d6)δ9.60(s,1H),8.65(t,J＝5.8Hz,1H),8.48(dd,J＝4.7,1.5Hz,1H),8.31(d,J＝1.8Hz,1H),8.24(dd,J＝8.1,1.5Hz,1H),7.69(d,J＝8.5Hz,1H),7.64(dd,J＝8.1,4.7Hz,1H),7.30(s,1H),7.26(d,J＝8.2Hz,1H),4.38–4.19(m,2H),1.46–1.40(m,2H),1.14–1.04(m,2H).
Example 35: preparation of N- (1- (benzylcarbamoyl) cyclopropyl) -3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide (Compound I-105)
Figure BDA0003352346640000401
The synthesis of the target compound was similar to 5.4, except that benzylamine and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carboxylic acid were used as starting materials in place of aniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid. The product was a white solid in 77.5% yield.
1H NMR(400MHz,DMSO-d6)δ9.60(s,1H),8.62(t,J＝5.9Hz,1H),8.47(dd,J＝4.7,1.5Hz,1H),8.23(dd,J＝8.1,1.5Hz,1H),7.62(dd,J＝8.1,4.7Hz,1H),7.30(s,1H),7.27–7.12(m,5H),4.37–4.22(m,2H),1.45–1.36(m,2H),1.15–1.06(m,2H).
Example 36: preparation of 3-bromo-N- (1- ((4-chlorobenzyl) carbamoyl) cyclopropyl) -1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide (Compound I-106)
Figure BDA0003352346640000402
The synthesis of the target compound was similar to 5.4, except that 4-chlorobenzylamine and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carboxylic acid were used as starting materials in place of aniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid. The product was a white solid, yield 71.2%.
1H NMR(400MHz,DMSO-d6)δ9.58(s,1H),8.65(t,J＝5.8Hz,1H),8.48(dd,J＝4.7,1.5Hz,1H),8.23(dd,J＝8.1,1.5Hz,1H),7.63(dd,J＝8.1,4.7Hz,1H),7.75(d,J＝8.4Hz,1H),7.29–7.15(m,5H),4.36–4.14(m,2H),1.44–1.33(m,2H),1.16–1.08(m,2H).
Example 37: preparation of 3-bromo-1- (3-chloropyridin-2-yl) -N- (1- (phenethylcarbamoyl) cyclopropyl) -1H-pyrazole-5-carboxamide (Compound I-113)
Figure BDA0003352346640000411
The synthesis of the target compound was similar to 5.4, except that phenethylamine and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carboxylic acid were used as starting materials instead of aniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid. The product was a white solid in 73.6% yield.
1H NMR(400MHz,DMSO-d6)δ9.62(s,1H),8.75(t,J＝5.4Hz,1H),8.45(dd,J＝4.7,1.5Hz,1H),8.20(dd,J＝8.1,1.5Hz,1H),7.60(dd,J＝8.1,4.7Hz,1H),7.30–7.10(m,6H),3.32–3.21(m,2H),2.69(t,J＝7.4Hz,2H),1.42–1.30(m,2H),1.13–1.02(m,2H).
Example 38: preparation of N- (1- (benzoylcarbamoyl) cyclopropyl) -3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide (Compound I-118)
Figure BDA0003352346640000412
1.11g (2.6mmol) of 3-bromo-1- (3-chloropyridin-2-yl) -N- (1-carbamoylcyclopropyl) -1H-pyrazole-5-carboxamide, 50mL of methylene chloride and 0.98g (8.0mmol) of 4-dimethylaminopyridine are successively placed in a 250mL three-necked flask. A solution of benzoyl chloride (0.42g, 3.0mmol) in dichloromethane (10mL) was added dropwise under ice-bath. After 8h reaction at 35 ℃ 80mL of water were added. The organic phase is separated off and the aqueous phase is extracted twice with 50mL of dichloromethane. The combined organic phases were dried over anhydrous sodium sulfate, the solvent was removed by rotary evaporation and the crude product was purified by column chromatography to give 0.95g of a white solid in 74.8% yield.
1H NMR(400MHz,DMSO-d6)δ11.54(s,1H),9.60(s,1H),8.49(dd,J＝4.7,1.5Hz,1H),8.27(dd,J＝8.1,1.5Hz,1H),7.87–7.78(m,2H),7.65(dd,J＝8.1,4.7Hz,1H),7.62–7.48(m,3H),7.31(s,1H),1.45–1.35(m,2H),1.16–1.09(m,2H).
Compounds I-116, I-117, I-119 to I-125, I-127, I-128, I-131 and I-132 were each synthesized in a similar manner to example 38, and the corresponding NMR's were as shown in Table II.
Example 39: preparation of N- (1- (benzoylcarbamoyl) cyclopropyl) -3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide (Compound I-126)
Figure BDA0003352346640000421
The synthesis of the title compound was similar to that of example 36, except that cinnamoyl chloride was used as the starting material instead of benzoyl chloride. The product was a white solid in 76.4% yield.
1H NMR(400MHz,DMSO-d6)δ11.22(s,1H),9.58(s,1H),8.47(dd,J＝4.7,1.5Hz,1H),8.23(dd,J＝8.1,1.5Hz,1H),7.73–7.54(m,4H),7.39–7.28(m,4H),1.43–1.36(m,2H),1.14–1.07(m,2H).
Example 40: preparation of 3-bromo-N- (1- ((3- (2-chloro-3, 3, 3-trifluoropropyl-1-en-1-yl) -2, 2-dimethylcyclopropane-1-carbonyl) carbamoyl) cyclopropyl) -1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide (Compound I-129)
40.13 preparation of- (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) -2, 2-dimethylcyclopropane-1-carbonyl chloride
Figure BDA0003352346640000422
The synthesis of the target compound was similar to 1.3, except that 3- (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) -2, 2-dimethylcyclopropane-1-carboxylic acid was used as the starting material instead of 3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxylic acid. The product was a yellow oily liquid with a yield of 95.7%.
Preparation of 23-bromo-N- (1- ((3- (2-chloro-3, 3, 3-trifluoropropyl-1-en-1-yl) -2, 2-dimethylcyclopropane-1-carbonyl) carbamoyl) cyclopropyl) -1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide
Figure BDA0003352346640000423
The synthesis of the title compound was carried out analogously to example 36, with the difference that the starting material was 3- (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) -2, 2-dimethylcyclopropane-1-carbonyl chloride instead of benzoyl chloride. The product was a white solid in 70.4% yield.
1H NMR(400MHz,DMSO-d6)δ11.42(s,1H),9.58(s,1H),8.47(dd,J＝4.7,1.5Hz,1H),8.22(dd,J＝8.1,1.5Hz,1H),7.62(dd,J＝8.1,4.7Hz,1H),7.28(s,1H),7.25–7.17(m,1H),2.23–2.18(m,1H),1.43–1.35(m,2H),1.32(s,3H),1.29(s,3H),1.16–1.07(m,2H).
Example 41: preparation of N- (1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carbonyl) -3- (difluoromethyl) -1-methyl-1H-pyrazole-4-carboxamide (Compound I-130)
Preparation of 13- (difluoromethyl) -1-methyl-1H-pyrazole-4-carbonyl chloride
Figure BDA0003352346640000431
The synthesis of the target compound was similar to 1.3, except that 3- (difluoromethyl) -1-methyl-1H-pyrazole-4-carboxylic acid was used as starting material instead of 3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxylic acid. The product was a yellow oily liquid with a yield of 96.5%.
Preparation of N- (1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carbonyl) -3- (difluoromethyl) -1-methyl-1H-pyrazole-4-carboxamide
Figure BDA0003352346640000432
The synthesis of the title compound was carried out analogously to example 36, with the difference that 2- (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) cyclopropane-1-carbonyl chloride was used as starting material instead of benzoyl chloride. The product was a white solid in 68.2% yield.
1H NMR(400MHz,DMSO-d6)δ11.61(s,1H),9.60(s,1H),8.47(dd,J＝4.7,1.5Hz,1H),8.21(dd,J＝8.1,1.5Hz,1H),7.96(s,1H),7.60(dd,J＝8.1,4.7Hz,1H),7.43(t,J＝52.7Hz,1H),7.35(s,1H),3.85(s,3H),1.48–1.40(m,2H),1.16–1.03(m,2H).
Example 42: preparation of 3-bromo-1- (3-chloropyridin-2-yl) -N- (1- ((4-chlorophenyl) carbamoyl) cyclopropyl) -1H-pyrazole-5-carboxamide (Compound I-136)
Figure BDA0003352346640000433
1.37g (3.2mmol) of 3-bromo-1- (3-chloropyridin-2-yl) -N- (1-carbamoylcyclopropyl) -1H-pyrazole-5-carboxamide, 80mL of toluene and 0.54g (3.5mmol) of p-chlorophenyl isocyanate were successively placed in a 250mL three-necked flask. After reacting at 110 ℃ for 8h, 150mL of water was added. The organic phase is separated off and the aqueous phase is extracted twice with 50mL of ethyl acetate. The combined organic phases were dried over anhydrous sodium sulfate, the solvent was removed by rotary evaporation and the crude product was purified by column chromatography to give the product as a white solid 1.07g with a yield of 62.2%.
1H NMR(400MHz,DMSO-d6)δ11.40(s,1H),9.57(s,1H),9.13(s,1H),8.45(dd,J＝4.7,1.5Hz,1H),8.22(dd,J＝8.1,1.5Hz,1H),7.62(dd,J＝8.1,4.7Hz,1H),7.45(d,J＝7.8,2H),7.28(s,1H),7.25(d,J＝7.8,2H),1.44–1.36(m,2H),1.12–1.04(m,2H).
Compounds I-133, I-134, I-135, I-138 and I-139 were each synthesized in a similar manner to example 42, and the corresponding NMR's are shown in Table II.
Example 43: preparation of 3-bromo-1- (3-chloropyridin-2-yl) -N- (1- ((4- (trifluoromethoxy) phenyl) carbamoyl) cyclopropyl) -1H-pyrazole-5-carboxamide (compound I-137)
Figure BDA0003352346640000441
The synthesis of the title compound was performed in a similar manner to example 40, except that 4-trifluoromethoxyphenyl isocyanate was used as the starting material in place of p-chlorophenyl isocyanate. The product was a white solid in 60.3% yield.
1H NMR(400MHz,DMSO-d6)δ11.35(s,1H),9.55(s,1H),9.08(s,1H),8.44(dd,J＝4.7,1.5Hz,1H),8.23(dd,J＝8.1,1.5Hz,1H),7.61(dd,J＝8.1,4.7Hz,1H),7.32–7.21(m,3H),7.04(d,J＝8.2,2H),1.44–1.36(m,2H),1.12–1.04(m,2H).
Example 44: preparation of N- (1- (2-acethydrazide-1-carbonyl) cyclopropyl) -3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide (Compound I-140)
Figure BDA0003352346640000442
The synthesis of the target compound was similar to 5.4, except that acetohydrazide and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carboxylic acid were used as starting materials in place of aniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid. The product was a white solid in 58.6% yield.
1H NMR(400MHz,DMSO-d6)δ10.47–10.42(m,1H),10.06–10.00(m,1H),9.14(s,1H),8.47(dd,J＝4.7,1.5Hz,1H),8.23(dd,J＝8.1,1.5Hz,1H),7.60(dd,J＝8.1,4.7Hz,1H),7.23(s,1H),3.98(s,3H),1.42–1.35(m,2H),1.12–1.04(m,2H).
Compounds I-141 and I-143 were synthesized in a similar manner to example 44, and the corresponding NMR's were as shown in Table II. Example 45: preparation of 3-bromo-1- (3-chloropyridin-2-yl) -N- (1- (2- (4-ethylbenzoyl) hydrazine-1-carbonyl) cyclopropyl) -1H-pyrazole-5-carboxamide (Compound I-142)
Figure BDA0003352346640000451
The synthesis of the title compound was similar to 5.4, except that ethyl benzoyl hydrazide and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carboxylic acid were used as starting materials instead of aniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid. The product was a white solid in 54.4% yield.
1H NMR(400MHz,DMSO-d6)δ10.62–10.55(m,1H),10.27–10.21(m,1H),9.18(s,1H),8.47(dd,J＝4.7,1.5Hz,1H),8.25(dd,J＝8.1,1.5Hz,1H),7.58(dd,J＝8.1,4.7Hz,1H),7.30–7.22(m,3H),7.12(d,J＝7.8Hz,2H),2.78–2.65(m,2H),1.59(t,J＝7.2Hz,3H),1.42–1.35(m,2H),1.12–1.04(m,2H).
Example 46: preparation of 3-bromo-1- (3-chloropyridin-2-yl) -N- (1- (dimethylcarbamoyl) cyclopropyl) -1H-pyrazole-5-carboxamide (Compound I-144)
Figure BDA0003352346640000452
The synthesis of the target compound was similar to 5.4, except that the starting materials were dimethylamine in tetrahydrofuran and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carboxylic acid instead of aniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid. The product was a white solid in 60.1% yield.
1H NMR(400MHz,DMSO-d6)δ9.58(s,1H),8.46(dd,J＝4.7,1.5Hz,1H),8.22(dd,J＝8.1,1.5Hz,1H),7.63(dd,J＝8.1,4.7Hz,1H),7.28(s,1H),3.08(s,3H),2.79(s,3H),1.44–1.38(m,2H),1.15–1.05(m,2H).
Example 47: preparation of 3-bromo-1- (3-chloropyridin-2-yl) -N- (1- (methyl (2,3, 3-trifluoroallyl) carbamoyl) cyclopropyl) -1H-pyrazole-5-carboxamide (Compound I-145)
Preparation of 13-bromo-1- (3-chloropyridin-2-yl) -N- (1- (methylcarbamoyl) cyclopropyl) -1H-pyrazole-5-carboxamide
Figure BDA0003352346640000461
The synthesis of the intermediate was similar to 5.4, except that methylamine and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carboxylic acid were used as starting materials instead of aniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid. The product was a white solid in 67.8% yield.
47.23 preparation of bromo-1- (3-chloropyridin-2-yl) -N- (1- (methyl (2,3, 3-trifluoroallyl) carbamoyl) cyclopropyl) -1H-pyrazole-5-carboxamide
Figure BDA0003352346640000462
The synthesis of the title compound was similar to 5.4, except that 3-bromo-1, 1, 2-trifluoroprop-1-ene and 3-bromo-1- (3-chloropyridin-2-yl) -N- (1- (methylcarbamoyl) cyclopropyl) -1H-pyrazole-5-carboxamide were used as starting materials instead of methyl iodide and 3-bromo-N- (2- (4-chlorophenyl) -1- (dimethylcarbamoyl) cyclopropyl) -1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide. The product was a white solid in 78.7% yield.
1H NMR(400MHz,DMSO-d6)δ9.75(s,1H),8.48(dd,J＝4.7,1.5Hz,1H),8.23(dd,J＝8.1,1.5Hz,1H),7.62(dd,J＝8.1,4.7Hz,1H),7.31(s,1H),4.10–3.97(m,1H),3.13(s,3H),1.48–1.41(m,2H),1.17–1.10(m,2H).
Example 48: preparation of N- (1- (benzyl (methyl) carbamoyl) cyclopropyl) -3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide (Compound I-146)
Figure BDA0003352346640000463
The synthesis of the title compound was similar to 5.4 except that benzyl bromide and 3-bromo-1- (3-chloropyridin-2-yl) -N- (1- (methylcarbamoyl) cyclopropyl) -1H-pyrazole-5-carboxamide were used as starting materials instead of methyl iodide and 3-bromo-N- (2- (4-chlorophenyl) -1- (dimethylcarbamoyl) cyclopropyl) -1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide. The product was a white solid in 82.4% yield.
1H NMR(400MHz,DMSO-d6)δ9.81(s,1H),8.49(dd,J＝4.7,1.5Hz,1H),8.24(dd,J＝8.1,1.5Hz,1H),7.63(dd,J＝8.1,4.7Hz,1H),7.31(s,1H),7.26–7.10(m,5H),4.28–4.15(m,2H),4.08–3.96(m,1H),3.08(s,3H),1.45–1.38(m,2H),1.14–1.07(m,2H).
Example 49: preparation of 3-bromo-1- (3-chloropyridin-2-yl) -N- (1- (diethylcarbamoyl) cyclopropyl) -N-methyl-1H-pyrazole-5-carboxamide (Compound I-147)
49.13 preparation of bromo-1- (3-chloropyridin-2-yl) -N- (1- (diethylcarbamoyl) cyclopropyl) -1H-pyrazole-5-carboxamide
Figure BDA0003352346640000471
The synthesis of the title compound was similar to 5.4, except that the starting materials were diethylamine in tetrahydrofuran and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carboxylic acid instead of aniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid. The product was a white solid in 72.6% yield.
Preparation of 23-bromo-1- (3-chloropyridin-2-yl) -N- (1- (diethylcarbamoyl) cyclopropyl) -N-methyl-1H-pyrazole-5-carboxamide
Figure BDA0003352346640000472
1.32g (3.0mmol) of 3-bromo-1- (3-chloropyridin-2-yl) -N- (1- (diethylcarbamoyl) cyclopropyl) -1H-pyrazole-5-carboxamide, 80mL of toluene, 0.47g (3.3mmol) of methyl iodide, and 1.46g (4.5mmol) of cesium carbonate were charged in that order to a 250mL three-necked flask. After 8h reaction at 50 ℃ 150mL of water was added. The organic phase is separated off and the aqueous phase is extracted twice with 50mL of ethyl acetate. The combined organic phases were dried over anhydrous sodium sulfate, the solvent was removed by rotary evaporation and the crude product was purified by column chromatography to give the product as a white solid 1.01g with a yield of 74.1%.
1H NMR(400MHz,DMSO-d6)δ8.46(dd,J＝4.7,1.5Hz,1H),8.21(dd,J＝8.1,1.5Hz,1H),7.58(dd,J＝8.1,4.7Hz,1H),7.26(s,1H),3.37–3.58(m,1H),3.40–3.26(m,2H),3.20–3.08(m,1H),3.05(s,3H),1.42–1.36(m,2H),1.16(d,J＝7.0Hz,3H),1.12–1.04(m,2H),0.96(d,J＝7.0Hz,3H).
Compound I-148 was synthesized according to the procedure for example 49, with the corresponding NMR as shown in Table II.
Example 50: preparation of N-benzyl-N- (1- (benzyl (phenyl) carbamoyl) cyclopropyl) -3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide (Compound I-150)
Figure BDA0003352346640000481
1.77g (3.5mmol) of 3-bromo-1- (3-chloropyridin-2-yl) -N- (1- (phenylcarbamoyl) cyclopropyl) -1H-pyrazole-5-carboxamide, 80mL of toluene, 1.44g (8.4mmol) of benzyl bromide, and 3.42g (10.5mmol) of cesium carbonate were charged in that order to a 250mL three-necked flask. After 8h reaction at 80 ℃ 150mL of water was added. The organic phase is separated off and the aqueous phase is extracted twice with 50mL of ethyl acetate. The combined organic phases were dried over anhydrous sodium sulfate, the solvent was removed by rotary evaporation and the crude product was purified by column chromatography to give the product as a white solid 0.93g with a yield of 41.4%.
1H NMR(400MHz,DMSO-d6)δ8.46(dd,J＝4.7,1.5Hz,1H),8.22(dd,J＝8.1,1.5Hz,1H),7.59(dd,J＝8.1,4.7Hz,1H),7.52–7.47(m,2H),7.30(s,1H),7.30–7.21(m,2H),7.16–7.01(t,J＝7.4Hz,11H),3.68–3.42(m,4H),1.43–1.36(m,2H),1.14–1.05(m,2H).
Compounds I-149 and I-151 were synthesized in a similar manner to example 50, and the corresponding NMR's are shown in Table II.
Example 51: preparation of 3-bromo-N- (1- (1- (tert-butyl) -2- (3-methoxy-2-methylbenzoyl) hydrazine-1-carbonyl) cyclopropyl) -1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide (Compound I-153)
Preparation of 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carbonyl) -2- (tert-butyl) hydrazine-1-carboxylic acid tert-butyl ester
Figure BDA0003352346640000482
The synthesis of the title compound was similar to 5.4, except that tert-butyl 2- (tert-butyl) hydrazine-1-carboxylate and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carboxylic acid were used as starting materials instead of aniline and 1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) -2-phenylcyclopropane-1-carboxylic acid. The product was a white solid in 65.9% yield.
51.23 preparation of bromo-N- (1- (1- (tert-butyl) hydrazine-1-carbonyl) cyclopropyl) -1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide
Figure BDA0003352346640000491
The synthesis of the target compound was similar to 1.2, except that the starting material was tert-butyl 2- (1- (3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamido) cyclopropane-1-carbonyl) -2- (tert-butyl) hydrazine-1-carboxylate instead of tert-butyl (1- (phenylcarbamoyl) cyclohexyl) carbamate. The product was a yellow oily liquid with a yield of 98.3%. The reaction is directly carried out without further treatment.
51.3 preparation of methoxy-2-methylbenzoyl chloride
Figure BDA0003352346640000492
The synthesis of the target compound was similar to 1.3, except that 3-methoxy-2-methylbenzoic acid was used as the starting material instead of 3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxylic acid. The product was a yellow oily liquid in 92.7% yield.
51.43 preparation of bromo-N- (1- (1- (tert-butyl) -2- (3-methoxy-2-methylbenzoyl) hydrazine-1-carbonyl) cyclopropyl) -1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide
Figure BDA0003352346640000493
The synthesis of the title compound was performed analogously to example 36, with the difference that 3-methoxy-2-methylbenzoyl chloride was reacted with 3-bromo-N- (1- (1- (tert-butyl) hydrazine-1-carbonyl) cyclopropyl) -1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide instead of benzoyl chloride with 3-bromo-1- (3-chloropyridin-2-yl) -N- (1-carbamoylcyclopropyl) -1H-pyrazole-5-carboxamide. The product was a white solid in 53.3% yield.
1H NMR(400MHz,DMSO-d6)δ10.01(s,1H),9.56(s,1H),8.45(dd,J＝4.7,1.5Hz,1H),8.20(dd,J＝8.1,1.5Hz,1H),7.61(dd,J＝8.1,4.7Hz,1H),7.28(s,1H),7.19(t,J＝8.8Hz,1H),7.04(d,J＝9.0Hz,1H),6.95(d,J＝8.8Hz,1H),3.82(s,3H),2.34(s,1H),1.41–1.32(m,2H),1.21–1.06(m,11H).
Compound I-152 was synthesized according to the procedure for example 51, with the corresponding NMR values shown in Table II.
Example 52: preparation of 3-bromo-N- (1- (1- (tert-butyl) -2- (3-methoxy-2-methylbenzoyl) hydrazine-1-carbonyl) cyclopropyl) -1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide (Compound I-155)
52.1 preparation of tert-butyl (1- (phenylcarbamoyl) cyclopropyl) carbamate
Figure BDA0003352346640000501
The synthesis of the target compound was similar to 1.1, except that 1- (tert-butoxycarbonyl) amino) cyclobutane-1-carboxylic acid was used as the starting material instead of 1- (tert-butoxycarbonyl) amino) cyclohexane-1-carboxylic acid. The product was a white solid in 78.7% yield.
52.21 preparation of amino-N-phenylcyclopropane-1-carboxamide
Figure BDA0003352346640000502
The synthesis of the target compound was similar to 1.2, except that t-butyl (1- (phenylcarbamoyl) cyclopropyl) carbamate was used as the starting material instead of t-butyl (1- (phenylcarbamoyl) cyclopropyl) carbamate. The product was a yellow oily liquid with a yield of 98.6%. The reaction is directly carried out without further treatment.
52.31- (3-Chloropyridin-2-yl) -3- (trifluoromethyl) -1H-pyrazole-5-carbonyl chloride preparation
Figure BDA0003352346640000503
The synthesis of the target compound was similar to 1.3, except that the starting material was 1- (3-chloropyridin-2-yl) -3- (trifluoromethyl) -1H-pyrazole-5-carboxylic acid instead of 3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxylic acid. The product was a yellow oily liquid with a yield of 94.6%.
52.43 preparation of trifluoromethyl-1- (3-chloropyridin-2-yl) -N- (1- (phenylcarbamoyl) cyclopropyl) -1H-pyrazole-5-carboxamide
Figure BDA0003352346640000504
The synthesis of the title compound was similar to 1.4, except that 1-amino-N-phenylcyclopropane-1-carboxamide and 1- (3-chloropyridin-2-yl) -3- (trifluoromethyl) -1H-pyrazole-5-carbonyl chloride were used as starting materials instead of 1-amino-N-phenylcyclohexane-1-carboxamide and 3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carbonyl chloride. The product was a white solid in 82.1% yield.
1H NMR(400MHz,DMSO-d6)δ9.57(s,1H),9.28(s,1H),8.46(dd,J＝4.7,1.5Hz,1H),8.22(dd,J＝8.1,1.5Hz,1H),7.63(dd,J＝8.1,4.7Hz,1H),7.55–7.48(m,2H),7.33–7.29(m,2H),7.04(t,J＝7.4Hz,1H),6.98(s,1H),1.44–1.37(m,2H),1.07–1.00(m,2H).
Compounds I-154, I-156, I-158, I-159, I-161 to I-165, I-167 to I-172, I-174 to I-177, I-179, I-180, I-182 to I-184, I-186 to I-188, and I-190 to I-192 were synthesized in a manner similar to that described in example 52, respectively, and the corresponding NMR's were shown in Table II.
Example 53: preparation of 3-bromo-N- (1- (1- (tert-butyl) -2- (3-methoxy-2-methylbenzoyl) hydrazine-1-carbonyl) cyclopropyl) -1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide (Compound I-157)
Preparation of 13- (tert-butyl) -1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carbonyl chloride
Figure BDA0003352346640000511
The synthesis of the target compound was similar to 1.3, except that 3- (tert-butyl) -1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxylic acid was used as the starting material instead of 3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxylic acid. The product was a yellow oily liquid in 92.4% yield.
Preparation of 23-bromo-N- (1- (1- (tert-butyl) -2- (3-methoxy-2-methylbenzoyl) hydrazine-1-carbonyl) cyclopropyl) -1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxamide
Figure BDA0003352346640000512
The synthesis of the title compound was similar to 1.4, except that 1-amino-N-phenylcyclopropane-1-carboxamide and 3- (tert-butyl) -1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carbonyl chloride were used as starting materials instead of 1-amino-N-phenylcyclohexane-1-carboxamide and 3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carbonyl chloride. The product was a white solid in 74.3% yield.
1H NMR(400MHz,DMSO-d6)δ9.49(s,1H),9.20(s,1H),8.43(dd,J＝4.7,1.5Hz,1H),8.23(dd,J＝8.1,1.5Hz,1H),7.61(dd,J＝8.1,4.7Hz,1H),7.53–7.46(m,2H),7.30–7.28(m,2H),7.05(t,J＝7.4Hz,1H),6.68(s,1H),1.56(s,9H),1.42–1.35(m,2H),1.05–0.96(m,2H).
Example 54: preparation of 1- (3-chloropyridin-2-yl) -3-phenyl-N- (1- (phenylcarbamoyl) cyclopropyl) -1H-pyrazole-5-carboxamide (Compound I-160)
54.1 preparation of 11- (3-Chloropyridin-2-yl) -3-phenyl-1H-pyrazole-5-carbonyl chloride
Figure BDA0003352346640000521
The synthesis of the target compound was similar to 1.3, except that the starting material was 1- (3-chloropyridin-2-yl) -3-phenyl-1H-pyrazole-5-carboxylic acid instead of 3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxylic acid. The product was a yellow oily liquid with a yield of 89.5%.
54.21- (3-Chloropyridin-2-yl) -3-phenyl-N- (1- (phenylcarbamoyl) cyclopropyl) -1H-pyrazole-5-carboxamide preparation
Figure BDA0003352346640000522
The synthesis of the title compound was similar to 1.4, except that 1-amino-N-phenylcyclopropane-1-carboxamide and 1- (3-chloropyridin-2-yl) -3-phenyl-1H-pyrazole-5-carbonyl chloride were used as starting materials instead of 1-amino-N-phenylcyclohexane-1-carboxamide and 3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carbonyl chloride. The product was a white solid in 67.4% yield.
1H NMR(400MHz,DMSO-d6)δ9.52(s,1H),9.24(s,1H),8.48(dd,J＝4.7,1.5Hz,1H),8.25(dd,J＝8.1,1.5Hz,1H),7.63(dd,J＝8.1,4.7Hz,1H),7.57–7.49(m,2H),7.33–7.19(m,4H),7.12–6.98(m,4H),1.45–1.37(m,2H),1.12–1.04(m,2H).
Example 55: preparation of 4-benzyl-1- (3-chloropyridin-2-yl) -3-methyl-N- (1- (phenylcarbamoyl) cyclopropyl) -1H-pyrazole-5-carboxamide (Compound I-166)
55.14 preparation of benzyl-1- (3-chloropyridin-2-yl) -3-methyl-1H-pyrazole-5-carbonyl chloride
Figure BDA0003352346640000531
The synthesis of the target compound was similar to 1.3, except that 4-benzyl-1- (3-chloropyridin-2-yl) -3-methyl-1H-pyrazole-5-carboxylic acid was used as the starting material instead of 3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxylic acid. The product was a yellow oily liquid with a yield of 86.9%.
55.24 preparation of benzyl-1- (3-chloropyridin-2-yl) -3-methyl-N- (1- (phenylcarbamoyl) cyclopropyl) -1H-pyrazole-5-carboxamide
Figure BDA0003352346640000532
The synthesis of the target compound was similar to 1.4, except that 1-amino-N-phenylcyclopropane-1-carboxamide and 4-benzyl-1- (3-chloropyridin-2-yl) -3-methyl-1H-pyrazole-5-carbonyl chloride were used as starting materials instead of 1-amino-N-phenylcyclohexane-1-carboxamide and 3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carbonyl chloride. The product was a white solid in 67.4% yield.
1H NMR(400MHz,DMSO-d6)δ9.57(s,1H),9.24(s,1H),8.47(dd,J＝4.7,1.5Hz,1H),8.23(dd,J＝8.1,1.5Hz,1H),7.63(dd,J＝8.1,4.7Hz,1H),7.53–7.46(m,2H),7.30–7.28(m,2H),7.12–7.04(m,6H),3.17(s,2H),2.55(s,3H),1.45–1.36(m,2H),1.12–1.03(m,2H).
Example 56: preparation of 1- (2-chlorophenyl) -3-methyl-N- (1- (methylcarbamoyl) cyclopropyl) -1H-pyrazole-5-carboxamide (Compound I-173)
56.1 preparation of tert-butyl (1- (methylcarbamoyl) cyclopropyl) carbamate
Figure BDA0003352346640000533
The synthesis of the target compound was similar to 1.1, except that methylamine hydrochloride and 1- (tert-butoxycarbonyl) amino) cyclobutane-1-carboxylic acid were used as starting materials instead of aniline and 1- (tert-butoxycarbonyl) amino) cyclohexane-1-carboxylic acid. The product was a white solid in 59.6% yield.
56.21 preparation of amino-N-methylcyclopropane-1-carboxamide
Figure BDA0003352346640000541
The synthesis of the target compound was similar to 1.2, except that t-butyl (1- (methylcarbamoyl) cyclopropyl) carbamate was used as the starting material instead of t-butyl (1- (phenylcarbamoyl) cyclopropyl) carbamate. The product was a yellow oily liquid with a yield of 90.7%. The reaction is directly carried out without further treatment.
56.1 preparation of 3-methyl-1H-pyrazole-5-carbonyl-2- (chlorophenyl) chloride
Figure BDA0003352346640000542
The synthesis of the target compound was similar to 1.3, except that the starting material was 1- (2-chlorophenyl) -3-methyl-1H-pyrazole-5-carboxylic acid instead of 3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxylic acid. The product was a yellow oily liquid in 92.4% yield.
56.41- (2-chlorophenyl) -3-methyl-N- (1- (methylcarbamoyl) cyclopropyl) -1H-pyrazole-5-carboxamide preparation
Figure BDA0003352346640000543
The synthesis of the target compound was similar to 1.4, except that 1-amino-N-methylcyclopropane-1-carboxamide and 1- (2-chlorophenyl) -3-methyl-1H-pyrazole-5-carbonyl chloride were used as starting materials instead of 1-amino-N-phenylcyclohexane-1-carboxamide and 3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carbonyl chloride. The product was a white solid in 65.3% yield.
1H NMR(400MHz,DMSO-d6)δ9.60(s,1H),8.62–8.56(m,1H),7.58–7.43(m,3H),7.32–7.26(m,1H),6.98(s,1H),2.57(d,J＝4.6Hz,3H),2.50(s,3H),1.42–1.35(m,2H),1.12–1.06(m,2H).
Example 57: preparation of 3-bromo-1- (3, 5-dichloropyridin-2-yl) -N- (1- (phenylcarbamoyl) cyclopropyl) -1H-pyrazole-5-carboxamide (Compound I-178)
57.13 preparation of bromo-1- (3, 5-dichloropyridin-2-yl) -1H-pyrazole-5-carbonyl chloride
Figure BDA0003352346640000551
The synthesis of the target compound was similar to 1.3, except that 3-bromo-1- (3, 5-dichloropyridin-2-yl) -1H-pyrazole-5-carboxylic acid was used as the starting material instead of 3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxylic acid. The product was a yellow oily liquid with a yield of 97.2%.
Preparation of 23-bromo-1- (3, 5-dichloropyridin-2-yl) -N- (1- (phenylcarbamoyl) cyclopropyl) -1H-pyrazole-5-carboxamide
Figure BDA0003352346640000552
The synthesis of the target compound was similar to 1.4, except that 1-amino-N-phenylcyclopropane-1-carboxamide and 3-bromo-1- (3, 5-dichloropyridin-2-yl) -1H-pyrazole-5-carbonyl chloride were used as starting materials instead of 1-amino-N-phenylcyclohexane-1-carboxamide and 3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carbonyl chloride. The product was a white solid in 67.4% yield.
1H NMR(400MHz,DMSO-d6)δ9.61(s,1H),9.11(s,1H),8.64(d,J＝1.3Hz,1H),8.45(d,J＝1.3Hz,1H),7.33–7.24(m,3H),7.15(t,J＝7.2Hz,1H),7.05(d,J＝7.8Hz,1H),1.48–1.41(m,2H),1.18–1.12(m,2H).
Example 58: preparation of 1- ([1,1' -biphenyl ] -3-yl) -3-bromo-N- (1- (phenylcarbamoyl) cyclopropyl) -1H-pyrazole-5-carboxamide (Compound I-181)
58.11 preparation of- ([1,1' -biphenyl ] -3-yl) -3-bromo-1H-pyrazole-5-carbonyl chloride
Figure BDA0003352346640000553
The synthesis of the target compound is similar to 1.3, except that the starting material is 1- ([1,1' -biphenyl ] -3-yl) -3-bromo-1H-pyrazole-5-carboxylic acid, instead of 3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxylic acid. The product was a yellow oily liquid in 93.6% yield.
Preparation of 58.21- ([1,1' -biphenyl ] -3-yl) -3-bromo-N- (1- (phenylcarbamoyl) cyclopropyl) -1H-pyrazole-5-carboxamide
Figure BDA0003352346640000561
The synthesis of the target compound was similar to 1.4, except that 1-amino-N-phenylcyclopropane-1-carboxamide and 1- ([1,1' -biphenyl ] -3-yl) -3-bromo-1H-pyrazole-5-carbonyl chloride were used as starting materials instead of 1-amino-N-phenylcyclohexane-1-carboxamide and 3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carbonyl chloride. The product was a white solid in 62.5% yield.
1H NMR(400MHz,DMSO-d6)δ9.60(s,1H),9.23(s,1H),7.98(s,1H),7.56–7.43(m,3H),7.41–7.20(m,8H),7.12(t,J＝7.2Hz,1H),7.03(d,J＝7.8Hz,1H),1.44–1.38(m,2H),1.12–1.04(m,2H).
Example 59: preparation of 3-bromo-1- (4 '-chloro- [1,1' -biphenyl ] -4-yl) -N- (1- (phenylcarbamoyl) cyclopropyl) -1H-pyrazole-5-carboxamide (Compound I-185)
Preparation of 13-bromo-1- (4 '-chloro- [1,1' -biphenyl ] -4-yl) -1H-pyrazole-5-carbonyl chloride
Figure BDA0003352346640000562
The synthesis of the target compound was similar to 1.3, except that 3-bromo-1- (4 '-chloro- [1,1' -biphenyl ] -4-yl) -1H-pyrazole-5-carboxylic acid was used as the starting material instead of 3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxylic acid. The product was a yellow oily liquid in 93.6% yield.
59.23 preparation of bromo-1- (4 '-chloro- [1,1' -biphenyl ] -4-yl) -N- (1- (phenylcarbamoyl) cyclopropyl) -1H-pyrazole-5-carboxamide
Figure BDA0003352346640000571
The synthesis of the target compound was similar to 1.4, except that 1-amino-N-phenylcyclopropane-1-carboxamide and 3-bromo-1- (4 '-chloro- [1,1' -biphenyl ] -4-yl) -1H-pyrazole-5-carbonyl chloride were used as starting materials instead of 1-amino-N-phenylcyclohexane-1-carboxamide and 3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carbonyl chloride. The product was a white solid in 60.2% yield.
1H NMR(400MHz,DMSO-d6)δ9.57(s,1H),9.28(s,1H),8.02–7.83(m,4H),7.71–7.45(m,6H),7.39–7.18(m,3H),7.09(d,J＝7.4Hz,1H),1.46–1.37(m,2H),1.16–1.09(m,2H).
Example 60: preparation of 3-bromo-N- (1- (phenylcarbamoyl) cyclopropyl) -1- (2,4, 6-tribromophenyl) -1H-pyrazole-5-carboxamide (Compound I-189)
60.13-bromo-1- (2,4, 6-tribromophenyl) -1H-pyrazole-5-carbonyl chloride preparation
Figure BDA0003352346640000572
The synthesis of the target compound was similar to 1.3, except that 3-bromo-1- (2,4, 6-tribromophenyl) -1H-pyrazole-5-carboxylic acid was used as the starting material instead of 3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carboxylic acid. The product was a yellow oily liquid with a yield of 95.5%.
60.23 preparation of bromo-N- (1- (phenylcarbamoyl) cyclopropyl) -1- (2,4, 6-tribromophenyl) -1H-pyrazole-5-carboxamide
Figure BDA0003352346640000573
The synthesis of the title compound was similar to 1.4, except that 1-amino-N-phenylcyclopropane-1-carboxamide and 3-bromo-1- (2,4, 6-tribromophenyl) -1H-pyrazole-5-carbonyl chloride were used as starting materials instead of 1-amino-N-phenylcyclohexane-1-carboxamide and 3-bromo-1- (3-chloropyridin-2-yl) -1H-pyrazole-5-carbonyl chloride. The product was a white solid in 73.8% yield.
1H NMR(400MHz,DMSO-d6)δ9.60(s,1H),9.30(s,1H),7.99(s,2H),7.53–7.44(m,2H),7.34–7.28(m,3H),7.04(t,J＝7.4Hz,1H),1.48–1.40(m,2H),1.10–1.02(m,2H).
Example 61: insecticidal Activity test of Compounds of the present invention
Experiment A Plutella xylostella
A group of culture dishes with the diameter of 6cm is taken, a layer of filter paper is covered on the bottom of the culture dish, and a proper amount of tap water is dripped for moisturizing. Cabbage leaves which were beaten into a leaf disk of 3cm in diameter were placed in each cup. Three cups were used in one set, each set being sprayed with only one liquid as described in test A. After the leaf surfaces are naturally dried in the shade, 10 third-instar larvae of the diamondback moth are put into each cup. The dishes were covered and left at 27 ℃ and 50% relative humidity for 72 hours before data collection. The mortality rate of the test insects at a compound concentration of 500ppm is shown in Table I.
Test B armyworm
A group of 260 ml cups was taken, and several sections of 2cm wide corn seedling leaves were placed in each cup. Three cups were used in one set, each set being sprayed with only one liquid as described in test A. After the leaf surfaces are naturally dried in the shade, 10 oriental armyworm third-instar larvae are placed in each cup. A piece of soaked gauze was inserted into each cup to prevent drying, each cup was covered, placed at 27 ℃ and 50% relative humidity for 72 hours, and data was collected. The mortality rate of the test insects at a compound concentration of 500ppm is shown in Table I.
The results show that compared with the prior pesticide compounds with similar structures, the compound of the invention has better pesticidal effect, and most compounds can cause 100 percent of death of tested pests at the concentration of 500 ppm.
Table I structure of the compounds of formula (I) and results of the insecticidal activity test
Figure BDA0003352346640000581
Figure BDA0003352346640000582
Figure BDA0003352346640000591
Figure BDA0003352346640000601
Figure BDA0003352346640000611
Figure BDA0003352346640000621
Figure BDA0003352346640000631
Figure BDA0003352346640000641
Figure BDA0003352346640000651
Figure BDA0003352346640000661
Figure BDA0003352346640000671
Table ii. part of the compounds1H NMR
Figure BDA0003352346640000681
Figure BDA0003352346640000691
Figure BDA0003352346640000701
Figure BDA0003352346640000711
Figure BDA0003352346640000721
Figure BDA0003352346640000731
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 (12)

1. A compound with a structure shown in a general formula (I), an optical isomer, a cis-trans isomer or an agriculturally and pharmaceutically acceptable salt thereof,
Figure FDA0003352346630000011
in the formula (I), the compound is shown in the specification,
n is 1,2, 3 or 4;
x is N or CR11；
m is 1,2, 3,4,5, 6, 7 or 8;
R1each independently selected from the group consisting of: hydrogen, halogen, cyano, nitro, C2–C6Ester group, C2–C6A sulfonate group, oxo (C ═ O), or a substituted or unsubstituted group selected from the group consisting of: c1–C6Alkyl radical, C2–C6Alkenyl radical, C2–C6Alkynyl, C3–C6Cycloalkyl, 4-8 membered heterocyclyl, C6–C10Aryl, 5-8 membered heteroaryl, -CONHR12；
R2Is hydrogen, or a substituted or unsubstituted group selected from: c1–C6Alkyl radical, C2–C6Alkenyl radical, C2–C6Alkynyl, C3–C6Cycloalkyl, 4-8 membered heterocyclyl, C6–C10Aryl, 5-8 membered heteroaryl, -COR13、–CONHR13、–NHCOR13；
R3、R4Each independently hydrogen, or a substituted or unsubstituted group selected from: c1–C6Alkyl radical, C2–C6Alkenyl radical, C2–C6Alkynyl, C3–C6Cycloalkyl, 4-8 membered heterocyclyl, C6–C10Aryl (I-146), 5-8 membered heteroaryl; wherein said substitution is by one or more groups selected from the group consisting of: halogen, cyano, nitro, C2–C6Ester group, C2–C6Sulfonate group, C1–C4Alkyl, 4-8 membered heterocyclic group, C6–C10Aryl, 5-8 membered heteroaryl, halo C1–C4Alkyl, halo C2–C4Alkenyl, halo C2–C4Alkynyl, halo C3–C5Cycloalkyl, halo C6–C10Aryl, halogenated 5-8 membered heteroaryl, C1–C4An alkoxy group;
R5、R6、R7、R8、R9、R10each independently of the others is hydrogen, halogen, cyano, nitro, C2–C6Ester group, C2–C6A sulfonate group, or a substituted or unsubstituted group selected from: c1–C6Alkyl radical, C2–C6Alkenyl radical, C2–C6Alkynyl, C3–C6Cycloalkyl, 4-8 membered heterocyclyl, C6–C10Aryl, 5-8 membered heteroaryl, C1–C6Alkoxy radical, C2–C6Alkenyloxy radical, C2–C6Alkynyloxy, C3–C6Cycloalkyl oxy, C6–C10Aryloxy, 5-8 membered heteroaryloxy, C1–C6Alkylthio radical, C2–C6Alkenylthio radical, C2–C6Alkynylthio, C3–C6Cycloalkylthio radical, C6–C10Arylthio, 5-to 8-membered heteroarylthio, C1–C6Alkylamino radical, C2–C6Enamine group, C2–C6Alkynylamino, C3–C6Cycloalkylamino group, C6–C10Arylamine group, 5-8 membered heteroaromatic amine group;
R11is hydrogen, halogen, cyano, nitro, C2–C6Ester group, C2–C6Sulfonate group, C1–C4Alkyl, 4-8 membered heterocyclic group, C6–C10Aryl, 5-8 membered heteroaryl;
R12is substituted or unsubstituted C1–C4Alkyl radical, C2–C4Alkenyl radical, C6–C10Aryl, 5-8 membered heteroaryl;
R13is substituted or unsubstituted C1–C4Alkyl radical, C2–C4Alkenyl radical, C3–C6Cycloalkyl, 4-8 membered heterocyclyl, C6–C10Aryl, 5-8 membered heteroaryl;
unless otherwise specified, the substitution refers to substitution by one or more groups selected from the group consisting of: halogen, cyano, nitro, C2–C6Ester group, C2–C6Sulfonate group, C1–C4Alkyl radical, C2–C4Alkenyl radical, C2–C4Alkynyl, C3–C5Cycloalkyl radical, C6–C10Aryl, 5-8 membered heteroaryl, halo C1–C3Alkyl, halo C2–C4Alkenyl, halo C2–C4Alkynyl, halo C3–C5Cycloalkyl, halo C6–C10Aryl, halogenated 5-8 membered heteroaryl, C1–C4Alkoxy radical, C2–C4Alkenyloxy radical, C2–C4Alkynyloxy, C3–C5Cycloalkyl oxy, C6–C10Aryloxy, 5-8 membered heteroaryloxy, C1–C4Alkylthio radical, C2–C4Alkenylthio radical, C2–C4Alkynylthio, C3–C5Cycloalkylthio radical, C6–C10Arylthio, 5-to 8-membered heteroarylthio, C1–C4Alkylamino radical, C2–C4Enamine group, C2–C4Alkynylamino, C3–C5Cycloalkylamino group, C6–C10Arylamine group and 5-8 membered heteroaromatic amine group.
2. The compound of claim 1, wherein the compound has a structure according to formula (III):
Figure FDA0003352346630000021
wherein, X, R1、R1’、R2、R3、R4、R5、R6、R7、R8、R9、R10As defined in claim 1.
3. The compound of claim 2, wherein the compound has a structure according to formula (III):
Figure FDA0003352346630000022
in the formula (I), the compound is shown in the specification,
x is N or CR11(ii) a Wherein R is11Is hydrogen, halogen, cyano, nitro, C1-C4Alkyl radical, C6-C10A phenyl group;
R1、R1' each is independently selected from the group consisting of: hydrogen, halogen, cyano, nitro, C2–C6Ester group, C2–C6A sulfonate group and a substituted or unsubstituted of: c1–C6Alkyl radical, C2–C6Alkenyl radical, C2–C6Alkynyl, C3–C6Cycloalkyl, 4-8 membered heterocyclyl, C6–C10Aryl, 5-8 membered heteroaryl, -CONHR12；
R5Is hydrogen, halogen, cyano, nitro, C2–C6Ester group, C2–C6A sulfonate group or a substituted or unsubstituted group selected from the group consisting of: c1–C4Alkyl radical, C2–C4Alkenyl radical, C6–C10An aryl group; wherein said substitution is by one or more groups selected from the group consisting of: halogen, cyano, nitro, C2–C6Ester group, C1–C4Alkyl radical, C6–C10Aryl, 5-8 membered heteroaryl;
R6is hydrogen, halogen, cyano, nitro, C2–C6Ester group, C2–C6A sulfonate group and a substituted or unsubstituted of: c1–C4Alkyl radical, C2–C4Alkenyl radical, C2–C4Alkynyl, C3–C6Cycloalkyl, 4-8 membered heterocyclyl, C6–C10Aryl, 5-8 membered heteroaryl, C1–C4Alkoxy radical, C2–C4Alkenyloxy radical, C2–C4Alkynyloxy, C3–C6Cycloalkyl oxy, C3–C6Cycloalkyl oxy, C6–C10Aryloxy, 5-8 membered heteroaryloxy, C1–C4Alkylthio radical, C2–C4Alkenylthio radical, C2–C4Alkynylthio, C3–C6Cycloalkylthio radical, C6–C10Arylthio, 5-8 membered heteroarylthio; wherein said substitution is by one or more groups selected from the group consisting of: halogen, cyano, nitro, C2–C6Ester group, C2–C6Sulfonate group, C1–C4Alkyl radical, C2–C4Alkenyl radical, C2–C4Alkynyl, C3–C5Cycloalkyl radical, C6–C10Aryl, 5-8 membered heteroaryl, halo C1–C4Alkyl, halo C2–C4Alkenyl, halo C2–C4Alkynyl, halo C3–C5Cycloalkyl, halo C6–C10Aryl, halo 5-8 membered heteroaryl;
R7、R9each independently selected from hydrogen, halogen, cyano, nitro, carboxyl, C2–C6Ester group, C2–C6A sulfonate group and a substituted or unsubstituted of: c1–C4Alkyl radical, C2–C4Alkenyl radical, C2–C4Alkynyl, C6–C10Aryl radical, C1–C4Alkoxy radical, C2–C4Alkenyloxy radical, C2–C4Alkynyloxy, C3–C5Cycloalkyl oxy, C6–C10Aryloxy, 5-8 membered heteroaryloxy, C1–C6Alkylthio radical, C2–C6Alkenylthio radical, C2–C6Alkynylthio, C3–C6Cycloalkylthio radical, C6–C10Arylthio, 5-8 membered heteroarylthio; wherein said substitution is by one or more groups selected from the group consisting of: halogen, cyano, nitro, C1-C4Alkyl, halo C1-C4An alkyl group;
R8、R10each independently hydrogen, halogen, and substituted or unsubstituted: c1–C4Alkyl radical, C2–C4Alkenyl radical, C1–C4Alkoxy radical, C2–C4An alkenyloxy group; wherein said substitution is by one or more groups selected from the group consisting of: halogen, cyano;
wherein R is12Is substituted or unsubstituted C1–C4Alkyl radical, C2–C4Alkenyl radical, C6–C10Aryl, 5-8 membered heteroaryl.
4. A compound according to claim 3, wherein X is N or CR11(ii) a Wherein R is11Hydrogen, halogen, cyano, nitro;
R1is hydrogen, halogen, cyano, nitro, C2–C6Ester group, C2–C6A sulfonate group and a substituted or unsubstituted of: c1–C6Alkyl radical, C2–C6Alkenyl radical, C2–C6Alkynyl, C3–C6Cycloalkyl, 4-8 membered heterocyclyl, C6–C10Aryl, 5-8 membered heteroaryl, -CONHR12；
R1' is hydrogen, halogen, cyano and substituted or unsubstitutedThe following groups of (a): 4-8 membered heterocyclic group, C6–C10Aryl, 5-8 membered heteroaryl, -CONHR12(ii) a Wherein R is12Is substituted or unsubstituted C1–C4Alkyl radical, C2–C4Alkenyl radical, C6–C10Aryl, 5-8 membered heteroaryl; wherein said substitution is by one or more groups selected from the group consisting of: halogen, cyano, C1–C4Alkyl, halo C1–C3An alkyl group;
R3、R4each independently hydrogen or a substituted or unsubstituted group selected from: c1–C6Alkyl radical, C2–C6Alkenyl radical, C6–C10An aryl group; wherein said substitution is by one or more groups selected from the group consisting of: halogen, cyano, nitro, C1–C4Alkyl radical, C2–C4Alkenyl radical, C6–C10Aryl, 5-8 membered heteroaryl, halo C1–C4Alkyl, halo C2–C4Alkenyl, halo C6–C10Aryl, halo 5-8 membered heteroaryl;
wherein R is12Is substituted or unsubstituted C1–C4Alkyl radical, C2–C4Alkenyl radical, C6–C10Aryl, 5-8 membered heteroaryl.
5. The compound of claim 1, wherein the compound has a structure according to formula (IV),
Figure FDA0003352346630000041
in the formula (I), the compound is shown in the specification,
x is N or CR11(ii) a Wherein R is11Hydrogen, halogen, cyano, nitro;
R1is hydrogen, halogen, cyano, nitro, C2–C6Ester group, C2–C6Sulfonic acid esterAnd substituted or unsubstituted groups selected from: c1–C6Alkyl radical, C2–C6Alkenyl radical, C2–C6Alkynyl, C3–C6Cycloalkyl, 4-8 membered heterocyclyl, C6–C10Aryl, 5-8 membered heteroaryl, -CONHR12(ii) a Wherein R is12Is substituted or unsubstituted C1–C4Alkyl radical, C2–C4Alkenyl radical, C6–C10Aryl, 5-8 membered heteroaryl; wherein said substitution is by one or more groups selected from the group consisting of: halogen, cyano, nitro, C2–C6Ester group, C2–C6Sulfonate group, C1–C4Alkyl radical, C2–C4Alkenyl radical, C2–C4Alkynyl, C3–C5Cycloalkyl radical, C6–C10Aryl, 5-8 membered heteroaryl, halo C1–C3Alkyl, halo C2–C4Alkenyl, halo C2–C4Alkynyl, halo C3–C5Cycloalkyl, halo C6–C10Aryl, halogenated 5-8 membered heteroaryl, C1–C4Alkoxy radical, C6–C10Aryloxy, 5-8 membered heteroaryloxy;
R2hydrogen and substituted or unsubstituted groups: c1–C6Alkyl radical, C2–C6Alkenyl radical, C2–C6Alkynyl, C3–C6Cycloalkyl, 4-8 membered heterocyclyl, C6–C10Aryl, 5-8 membered heteroaryl, -COR13、–CONHR13、–NHCOR13(ii) a Wherein R is13Is substituted or unsubstituted C1–C4Alkyl radical, C2–C4Alkenyl radical, C3–C6Cycloalkyl radical, C6–C10Aryl, 5-8 membered heteroaryl; wherein said substitution is by one or more groups selected from the group consisting of: halogen, cyano, nitro, C2–C6Ester group, C2–C6Sulfonate group, C1–C4Alkyl radical, C2–C4Alkenyl radical, C2–C4Alkynyl, C3–C5Cycloalkyl radical, C6–C10Aryl, 5-8 membered heteroaryl, halo C1–C4Alkyl, halo C2–C4Alkenyl, halo C2–C4Alkynyl, halo C3–C5Cycloalkyl, halo C6–C10Aryl, halogenated 5-8 membered heteroaryl, C1–C4Alkoxy radical, C6–C10Aryloxy radical, C1–C4Alkylamino radical, C6–C10Arylthio group, C1–C4An alkylthio group;
R3、R4each independently hydrogen or a substituted or unsubstituted group: c1–C6Alkyl radical, C2–C6Alkenyl radical, C6–C10An aryl group; wherein said substitution is by one or more groups selected from the group consisting of: halogen, cyano, C1–C4An alkyl group;
R5is hydrogen, halogen, cyano, nitro, C2–C6An ester group;
R7、R9each independently of the others is hydrogen, halogen, cyano, nitro, C2–C6An ester group and a substituted or unsubstituted group: c1–C4Alkyl radical, C2–C4Alkenyl radical, C2–C4Alkynyl, C6–C10Aryl radical, C1–C4Alkoxy radical, C2–C4Alkenyloxy radical, C2–C4Alkynyloxy, C6–C10Aryloxy, 5-8 membered heteroaryloxy, C1–C6Alkylthio radical, C2–C6Alkenylthio radical, C2–C6Alkynylthio, C6–C10Arylthio, 5-8 membered heteroarylthio; wherein said substitution is by one or more groups selected from the group consisting of: halogen, cyano, nitro.
6. The compound of claim 5,
R1is hydrogen, halogen, cyano, nitro, C2–C6Ester group, C2–C6A sulfonate group and a substituted or unsubstituted of: c1–C6Alkyl radical, C2–C6Alkenyl radical, C2–C6Alkynyl, 4-8 membered heterocyclyl, C6–C10Aryl, 5-8 membered heteroaryl;
R2hydrogen and substituted or unsubstituted groups: c1–C6Alkyl radical, C2–C6Alkenyl radical, C2–C6Alkynyl, C3–C6Cycloalkyl, 4-8 membered heterocyclyl, C6–C10Aryl, 5-8 membered heteroaryl, -COR13、–CONHR13、–NHCOR13(ii) a Wherein R is13Is substituted or unsubstituted C1–C4Alkyl radical, C2–C4Alkenyl radical, C3–C6Cycloalkyl radical, C6–C10Aryl, 5-8 membered heteroaryl;
R6is hydrogen, halogen, cyano, nitro, C2–C6Ester group, C2–C6A sulfonate group and a substituted or unsubstituted of: c1–C4Alkyl radical, C2–C4Alkenyl radical, C2–C4Alkynyl, C3–C6Cycloalkyl radical, C6–C10Aryl, 4-8 membered heterocyclic group, C1–C4An alkoxy group; wherein said substitution is by one or more groups selected from the group consisting of: halogen, cyano, C1–C4Alkyl radical, C6–C10Aryl, 5-8 membered heteroaryl, halo C6–C10Aryl, halo 5-8 membered heteroaryl;
R7、R9each independently hydrogen, halogen, cyano, nitro, carboxyl, and substituted or unsubstituted: c6–C10Aryl radical, C1–C4Alkoxy radical, C6–C10Aryloxy groupRadical, 5-to 8-membered heteroaryloxy, C1–C6An alkylthio group; wherein said substitution is by one or more groups selected from the group consisting of: halogen, cyano;
R8、R10each independently hydrogen, halogen.
7. The compound of claim 6, wherein the compound has a structure according to formula (V),
Figure FDA0003352346630000061
in the formula (I), the compound is shown in the specification,
R1is hydrogen, halogen, cyano, C2–C6An ester group and a substituted or unsubstituted group: c1–C6Alkyl radical, C2–C6Alkenyl radical, C2–C6Alkynyl, 4-8 membered heterocyclyl, C6–C10Aryl, 5-8 membered heteroaryl; wherein said substitution is by one or more groups selected from the group consisting of: halogen, cyano, nitro, C2–C6Ester group, C1–C4Alkyl radical, C2–C4Alkenyl radical, C2–C4Alkynyl, C6–C10Aryl, 5-8 membered heteroaryl, halo C1–C3Alkyl, halo C2–C4Alkenyl, halo C2–C4Alkynyl, halo C6–C10Aryl, halogenated 5-8 membered heteroaryl, C1–C4Alkoxy radical, C6–C10An aryloxy group;
R2hydrogen and substituted or unsubstituted groups: c1–C6Alkyl radical, C2–C6Alkenyl radical, C2–C6Alkynyl, C3–C6Cycloalkyl, 4-8 membered heterocyclyl, C6–C10Aryl, 5-8 membered heteroaryl, -COR13、–CONHR13、–NHCOR13(ii) a Wherein R is13Is substituted or unsubstituted C1–C4Alkyl radical, C2–C4Alkenyl radical, C3–C6Cycloalkyl radical, C6–C10Aryl, 5-8 membered heteroaryl; wherein said substitution is by one or more groups selected from the group consisting of: halogen, cyano, C2–C6Ester group, C1–C4Alkyl radical, C2–C4Alkenyl radical, C2–C4Alkynyl, C3–C5Cycloalkyl radical, C6–C10Aryl, 5-8 membered heteroaryl, halo C1–C4Alkyl, halo C2–C4Alkenyl, halo C2–C4Alkynyl, halo C3–C5Cycloalkyl, halo C6–C10Aryl, halogenated 5-8 membered heteroaryl, C1–C4Alkoxy radical, C6–C10Aryloxy radical, C1–C4Alkyl amine, C6–C10Arylthio group, C1–C4An alkylthio group;
R6is hydrogen, halogen, cyano, nitro, C2–C6An ester group and a substituted or unsubstituted group: c1–C4Alkyl radical, C3–C6Cycloalkyl radical, C6–C10Aryl (I-172, 165), C1–C4An alkoxy group; wherein said substitution is by one or more groups selected from the group consisting of: halogen, C1–C4An alkyl group;
R7，R9each independently selected from the group consisting of: hydrogen, halogen, cyano, carboxyl and substituted or unsubstituted: c6–C10Aryl radical, C1–C4Alkoxy radical, C6–C10Aryloxy radical, C1–C6Alkylthio, 5-8 membered heteroarylthio; wherein said substitution is by one or more groups selected from the group consisting of: halogen, C1-C4An alkyl group.
8. The compound of claim 7, wherein the compound is selected from the group consisting ofIn that R1Selected from hydrogen, halogen, cyano, C2–C6An ester group and a substituted or unsubstituted group: c2–C6Alkenyl radical, C6–C10Aryl, 5-8 membered heteroaryl; wherein said substitution is by one or more groups selected from the group consisting of: halogen, cyano, nitro, C2–C6Ester group, C1–C4Alkyl radical, C6–C10Aryl, halo C1–C3Alkyl radical, C1–C4Alkoxy radical, C6–C10An aryloxy group;
R2hydrogen and substituted or unsubstituted groups: c1–C6Alkyl radical, C2–C6Alkenyl radical, C2–C6Alkynyl, C3–C6Cycloalkyl, 4-8 membered heterocyclyl, C6–C10Aryl, 5-8 membered heteroaryl, -COR13、–CONHR13、–NHCOR13(ii) a Wherein R is13Is substituted or unsubstituted C1–C4Alkyl radical, C2–C4Alkenyl radical, C3–C6Cycloalkyl radical, C6–C10Aryl, 5-8 membered heteroaryl; wherein said substitution is by one or more groups selected from the group consisting of: halogen, cyano, C2–C6Ester group, C1–C4Alkyl radical, C2–C4Alkenyl radical, C2–C4Alkynyl, C3–C5Cycloalkyl radical, C6–C10Aryl, 5-8 membered heteroaryl, halo C1–C4Alkyl, halo 5-8 membered heteroaryl, C1–C4Alkoxy radical, C6–C10Aryloxy radical, C1–C4Alkylamino radical, C6–C10Arylthio group, C1–C4An alkylthio group;
R6、R7、R9as defined in claim 7.
9. The compound of claim 1, wherein the compound is selected from the group consisting of: compounds I-1 to I-192 in Table I.
10. A pesticidal composition which comprises (1) a compound having a structure represented by the general formula (I) according to claim 1, an optical isomer, a cis-trans isomer thereof, or an agriculturally pharmaceutically acceptable salt thereof; and (2) an agriculturally pharmaceutically acceptable carrier or excipient.
11. The use of a compound of the general formula (I), an optical isomer, a cis-trans isomer or an agriculturally and pharmaceutically acceptable salt thereof according to claim 1 or a pesticidal composition according to claim 10,
(i) for the preparation of insecticides; or
(ii) Is used for preventing and controlling agricultural and forestry and horticultural plant insect pests.
12. A method for controlling insect pests, characterized by applying a compound having a structure represented by the general formula (I), an optical isomer, a cis-trans isomer or an agriculturally and pharmaceutically acceptable salt thereof according to claim 1, or the pesticidal composition according to claim 10 to the environment, soil or agricultural and forestry and horticultural plants to be controlled.
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