CN110452167A - Quinoline derivatives and its preparation method and application - Google Patents

Quinoline derivatives and its preparation method and application Download PDF

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Publication number
CN110452167A
CN110452167A CN201810338820.XA CN201810338820A CN110452167A CN 110452167 A CN110452167 A CN 110452167A CN 201810338820 A CN201810338820 A CN 201810338820A CN 110452167 A CN110452167 A CN 110452167A
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alkyl
aryl
halogenated
alkoxy
hydrogen
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CN110452167B (en
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李义涛
林健
姚文强
王发平
徐俊星
陈涛
李法霖
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Dongguan Dongyangguang Pesticide R & D Co Ltd
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Dongguan Dongyangguang Pesticide R & D Co Ltd
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    • 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
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
    • A01N43/42—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings condensed with carbocyclic rings
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/60—1,4-Diazines; Hydrogenated 1,4-diazines
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A01N43/76—1,3-Oxazoles; Hydrogenated 1,3-oxazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A01N43/78—1,3-Thiazoles; Hydrogenated 1,3-thiazoles
    • 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
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/02—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having no bond to a nitrogen atom
    • 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
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/02—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having no bond to a nitrogen atom
    • A01N47/06—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having no bond to a nitrogen atom containing —O—CO—O— groups; Thio analogues thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D215/20—Oxygen atoms
    • C07D215/22—Oxygen atoms attached in position 2 or 4
    • C07D215/233—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 4
    • 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
    • C07D401/12—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 linked by a chain containing hetero atoms as chain links
    • 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
    • C07D405/02—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 two hetero rings
    • C07D405/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

Abstract

The present invention provides a kind of quinoline derivatives, and the composition comprising the analog derivative.The present invention also provides the purposes that the method for preparing the analog derivative and the analog derivative and composition kill pest.

Description

Quinoline derivatives and its preparation method and application
Technical field
The present invention relates to the quinoline derivatives and its nitrogen oxides and salt for pest control.
Background technique
The now agriculture long-time due to pesticide uses, and the pest on crop makes existing agriculture to which create drug resistances Medicine control efficiency is substantially reduced, and in order to solve this problem, needs to continually develop the new compound for providing insecticidal activity.
Summary of the invention
The present invention provides a kind of quinoline derivatives, and the composition comprising this analog derivative, the quinoline derivatives And combinations thereof for preventing and treating pest on useful plant.
Specifically:
On the one hand, the present invention provides a kind of alloisomerism of compound as shown in formula (A) compound represented or formula (A) Body, nitrogen oxides and its acceptable salt:
Wherein:
R1For hydrogen, C1-6Alkyl, halogenated C1-6Alkyl, C2-6Alkenyl or C1-6Alkoxy；
R2For hydrogen or C1-6Alkyl；
R3For hydrogen, C1-6Alkyl, amino-C1-6Alkylidene-, C6-14Aryl, C6-14Aryl-C1-6Alkylidene-,-(C=O) R6 Or-SO2R7；Wherein, R3Optionally X is selected from by 1,2,3,4,5 or 61Substituent group replace；
Wherein, R6For C1-6Alkyl, C2-6Alkenyl, C2-6Alkynyl, C3-10Naphthenic base, C6-14Aryl, C6-14Aryl-C1-6Alkylene Base-, 3-10 circle heterocyclic ring base, 5-10 unit's heteroaryl ,-OR8Or-NRnRm；
Wherein, R7For C1-6Alkyl, C3-10Naphthenic base, C6-14Aryl, 5-10 unit's heteroaryl or-NRnRm；
Wherein, R8For C1-6Alkyl, C2-6Alkenyl, C2-6Alkynyl, C3-10Naphthenic base, 3-10 circle heterocyclic ring base, 5-10 unit's heteroaryl, C6-14Aryl or C6-14Aryl-C1-6Alkylidene-；
Wherein, each RnAnd RmIt independently is hydrogen, C1-6Alkyl, C3-10Naphthenic base, C6-14Aryl or 5-10 unit's heteroaryl；
Or Rn、Rm3-10 circle heterocyclic ring base is formed with connected nitrogen-atoms；
Wherein, X1For halogen, nitro, cyano, oxo (=O), hydroxyl, amino, C1-6Alkyl, C2-6Alkenyl, C2-6Alkynyl, Halogenated C1-6Alkyl, halogenated C2-6Alkenyl, halogenated C2-6Alkynyl, C1-6Alkoxy, halogenated C1-6Alkoxy, C3-8Naphthenic base, C6-14Virtue Base, halogenated C6-14Aryl, C6-14Aryloxy, 5-10 unit's heteroaryl or halogenated 5-10 unit's heteroaryl；
Or X1For following subformula:
Wherein, each RxIt independently is halogen or C1-6Alkyl；
P is 0,1,2,3 or 4；
Ay is C6-14Aryl or 5-10 unit's heteroaryl；The wherein C6-14Aryl or 5-10 unit's heteroaryl are optionally by halogen Element, C1-6Alkyl or C1-6Alkoxy replaces；
R4aFor hydrogen, halogen, cyano, C1-6Alkyl, halogenated C1-6Alkyl, C1-6Alkoxy, C1-6Alkyl-(C=O)-, C1-6Alkane Oxygroup-(C=O)-or C1-6Alkyl-(C=O)-O-；
R4bFor hydrogen, halogen, C1-6Alkyl, halogenated C1-6Alkyl, C1-6Alkoxy, C1-6Alkyl-(C=O)-, C1-6Alkoxy- (C=O)-or C1-6Alkyl-(C=O)-O-；
R4cFor hydrogen, halogen, C1-6Alkyl, halogenated C1-6Alkyl or C1-6Alkoxy；
Condition are as follows: R4a、R4bAnd R4cIt is not simultaneously hydrogen；
Q is 0,1,2,3 or 4；
Each R5It independently is halogen, nitro, cyano, C1-6Alkyl, halogenated C1-6Alkyl, C1-6Alkoxy or halogenated C1-6Alcoxyl Base；
Y is key ,-O- ,-S- ,-O (CR9R10)n-L1Or-NR11-L2-；
Wherein, R9And R10It is each independently hydrogen or C1-6Alkyl；
Or R9、R10C=O is formed with the carbon atom being connected；
N is 1,2 or 3；
L1Linear chain or branched chain for key or containing 1,2,3,4,5 or 6 carbon atom；
R11For hydrogen or C1-6Alkyl；
L2For key, C=O or SO2；
Z is C6-14Aryl or 5-10 unit's heteroaryl；Wherein, Z is optionally selected from X by 1,2,3,4,5,6,7 or 82Substitution Base replaces；
Wherein, X2For halogen, nitro, cyano, hydroxyl, amino, C1-6Alkyl, halogenated C1-6Alkyl, C2-6Alkenyl, C1-6Alcoxyl Base, halogenated C1-6Alkoxy, C6-14Aryl or halogenated C6-14Aryl；
Condition are as follows:
1) formula (A) compound represented does not include compound 2,3- dimethyl -5- (trifluoromethyl) -6- (4- (4- (trifluoromethyl) phenoxy group) phenoxy group) quinolyl-4 acetic acid esters, 2,3- dimethyl -7- (trifluoromethyl) -6- (4- (4- (trifluoro Methyl) phenoxy group) phenoxy group) quinolyl-4 acetic acid esters, 2,3- dimethyl -5- (trifluoromethyl) -6- ((4'- (trifluoromethyl) - [1,1'- biphenyl] -4- base) oxygroup) quinolyl-4 acetic acid esters and 2,3- dimethyl -7- (trifluoromethyl) -6- ((4'- (fluoroform Base)-[1,1'- biphenyl] -4- base) oxygroup) quinolyl-4 acetic acid esters；
2) as R in formula (A) compound represented3For-(C=O) R6, R6For-OR8, R8For C1-4Alkyl, R1For C1-4 Alkyl, R2For C1-4Alkyl, R4cFor hydrogen, when q 0, Y are O, Z is not 5- trifluoromethyl -2- pyridyl group or 3- halogen -5- fluoroform Base -2- pyridyl group.
In some embodiments, R1For hydrogen, C1-4Alkyl, halogenated C1-4Alkyl, C2-4Alkenyl or C1-4Alkoxy；
R2For hydrogen or C1-4Alkyl；
R3For hydrogen, C1-4Alkyl, amino-C1-4Alkylidene-, C6-10Aryl, C6-10Aryl-C1-4Alkylidene-,-(C=O) R6 Or-SO2R7；Wherein, R3Optionally X is selected from by 1,2,3,4,5 or 61Substituent group replace；
Wherein, R6For C1-4Alkyl, C2-4Alkenyl, C2-4Alkynyl, C3-6Naphthenic base, C6-10Aryl, C6-10Aryl-C1-4Alkylene Base-, 3-10 circle heterocyclic ring base, 5-10 unit's heteroaryl ,-OR8Or-NRnRm；
Wherein, R7For C1-4Alkyl, C3-6Naphthenic base, C6-10Aryl, 5-10 unit's heteroaryl or-NRnRm；
Wherein, R8For C1-4Alkyl, C2-4Alkenyl, C2-4Alkynyl, C3-6Naphthenic base, 3-10 circle heterocyclic ring base, 5-10 unit's heteroaryl, C6-10Aryl or C6-10Aryl-C1-4Alkylidene-；
Wherein, each RnAnd RmIt independently is hydrogen, C1-4Alkyl, C3-6Naphthenic base, C6-10Aryl or 5-10 unit's heteroaryl；
Or Rn、Rm3-10 circle heterocyclic ring base is formed with connected nitrogen-atoms；
Wherein, X1For halogen, nitro, cyano, oxo (=O), hydroxyl, amino, C1-4Alkyl, C2-4Alkenyl, C2-4Alkynyl, Halogenated C1-4Alkyl, halogenated C2-4Alkenyl, halogenated C2-4Alkynyl, C1-4Alkoxy, halogenated C1-4Alkoxy, C3-6Naphthenic base, C6-10Virtue Base, halogenated C6-10Aryl, C6-10Aryloxy, 5-10 unit's heteroaryl or halogenated 5-10 unit's heteroaryl；
Or X1For following subformula:
Wherein, each RxIt independently is halogen or C1-4Alkyl；
P is 0,1,2,3 or 4；
Ay is C6-12Aryl or 5-10 unit's heteroaryl；The wherein C6-12Aryl or 5-10 unit's heteroaryl are optionally by halogen Element, C1-4Alkyl or C1-4Alkoxy replaces；
R4aFor hydrogen, halogen, cyano, C1-4Alkyl, halogenated C1-4Alkyl, C1-4Alkoxy, C1-4Alkyl-(C=O)-, C1-4Alkane Oxygroup-(C=O)-or C1-4Alkyl-(C=O)-O-；
R4bFor hydrogen, halogen, C1-4Alkyl, halogenated C1-4Alkyl, C1-4Alkoxy, C1-4Alkyl-(C=O)-, C1-4Alkoxy- (C=O)-or C1-4Alkyl-(C=O)-O-；
R4cFor hydrogen, halogen, C1-4Alkyl, halogenated C1-4Alkyl or C1-4Alkoxy.
Also in some embodiments, R1For hydrogen, C1-4Alkyl or halogenated C1-4Alkyl；
R2For hydrogen or C1-4Alkyl；
R3For hydrogen, C1-4Alkyl, amino-C1-4Alkylidene-, C6-10Aryl, C6-10Aryl-C1-4Alkylidene-,-(C=O) R6 Or-SO2R7；Wherein, R3Optionally X is selected from by 1,2,3,4,5 or 61Substituent group replace；
Wherein, R6For C1-4Alkyl, C2-4Alkenyl, C3-6Naphthenic base, C6-10Aryl, C6-10Aryl-C1-4Alkylidene-, 5-10 member Heteroaryl ,-OR8Or-NRnRm；
Wherein, R7For C1-4Alkyl, C3-6Naphthenic base, C6-10Aryl, 5-10 unit's heteroaryl or-NRnRm；
Wherein, R8For C1-4Alkyl or C6-10Aryl；
Wherein, each RnAnd RmIt independently is hydrogen, C1-4Alkyl or C3-6Naphthenic base；
Or Rn、Rm3-10 circle heterocyclic ring base is formed with connected nitrogen-atoms；
Wherein, X1For halogen, nitro, cyano, oxo (=O), hydroxyl, amino, C1-4Alkyl, C2-4Alkenyl, C2-4Alkynyl, Halogenated C1-4Alkyl, halogenated C2-4Alkenyl, halogenated C2-4Alkynyl, C1-4Alkoxy, halogenated C1-4Alkoxy, C3-6Naphthenic base, C6-10Virtue Base, halogenated C6-10Aryl, C6-10Aryloxy, 5-10 unit's heteroaryl or halogenated 5-10 unit's heteroaryl；
Or X1For following subformula:
Wherein, each RxIt independently is halogen or C1-4Alkyl；
P is 0,1,2,3 or 4；
Ay is C6-10Aryl or 5-10 unit's heteroaryl；The wherein C6-10Aryl or 5-10 unit's heteroaryl are optionally by halogen Element, C1-4Alkyl or C1-4Alkoxy replaces；
R4aFor hydrogen, halogen, cyano, C1-4Alkyl, halogenated C1-4Alkyl, C1-4Alkoxy or C1-4Alkoxy-(C=O)-；
R4bFor hydrogen, halogen, C1-4Alkyl, halogenated C1-4Alkyl, C1-4Alkoxy or C1-4Alkoxy-(C=O)-；
R4cFor hydrogen, halogen, C1-4Alkyl or halogenated C1-4Alkyl.
Also in a more another embodiments, R1For hydrogen ,-CH3、-CH2CH3、-CH(CH3)2、-C(CH3)3、-CHF2Or-CF3。
Also in a more another embodiments, R2For hydrogen ,-CH3、-CH2CH3Or-C (CH3)3。
Also in a more another embodiments, R3For following subformula:
Also in a more another embodiments, R4aFor hydrogen, fluorine, chlorine, bromine, cyano ,-CH3、-CH2CH3、-CF3、-OCH3Or-C (= O)OCH3。
Also in a more another embodiments, R4bFor hydrogen, fluorine, chlorine, bromine ,-CH3、-CH2CH3、-CHF2、-CF3、-OCH3Or-C (= O)OCH3。
Also in a more another embodiments, R4cFor hydrogen, fluorine, chlorine, bromine ,-CH3Or-CF3。
In some embodiments, 0,1,2,3 or 4 q；
Each R5It independently is halogen, nitro, cyano, C1-4Alkyl, halogenated C1-4Alkyl, C1-4Alkoxy or halogenated C1-4Alcoxyl Base；
Y is key ,-O- ,-S- ,-O (CR9R10)n-L1Or-NR11-L2-；
Wherein, R9And R10It is each independently hydrogen or C1-4Alkyl；
Or R9、R10C=O is formed with the carbon atom being connected；
N is 1,2 or 3；
L1Linear chain or branched chain for key or containing 1,2,3,4,5 or 6 carbon atom；
R11For hydrogen or C1-4Alkyl；
L2For key, C=O or SO2；
Z is C6-10Aryl or 5-10 unit's heteroaryl；Wherein, Z is optionally selected from X by 1,2,3,4,5,6,7 or 82Substitution Base replaces；
Wherein, X2For halogen, nitro, cyano, hydroxyl, amino, C1-4Alkyl, halogenated C1-4Alkyl, C2-4Alkenyl, C1-4Alcoxyl Base, halogenated C1-4Alkoxy, C6-10Aryl or halogenated C6-10Aryl.
Also in some embodiments, 0,1,2,3 or 4 q；
Each R5It independently is halogen or C1-4Alkyl；
Y is key ,-O- ,-S- ,-O (CR9R10)n-L1Or-NR11-L2-；
Wherein, R9And R10It is each independently hydrogen；
Or R9、R10C=O is formed with the carbon atom being connected；
N is 1 or 2；
L1Linear chain or branched chain for key or containing 1,2 or 3 carbon atom；
R11For hydrogen；
L2For key, C=O or SO2；
Z is C6-10Aryl or 5-10 unit's heteroaryl；Wherein, Z is optionally selected from X by 1,2,3,4,5,6,7 or 82Substitution Base replaces；
Wherein, X2For halogen, nitro, cyano, hydroxyl, amino, C1-4Alkyl, halogenated C1-4Alkyl, C2-4Alkenyl, C1-4Alcoxyl Base, halogenated C1-4Alkoxy, C6-10Aryl or halogenated C6-10Aryl.
Also in further embodiments, each R5It independently is fluorine, chlorine, bromine ,-CH3Or-CH2CH3。
Also in further embodiments, Y is key ,-O- ,-O (C=O)-,-O (C=O)-CH=CH- or-NH- (C=O)-.
Also in further embodiments, Z is following subformula:
In some embodiments, the present invention provides a kind of standing for compound as shown in formula (B) compound represented or formula (B) Body isomers, nitrogen oxides and its acceptable salt:
Condition are as follows:
1) formula (B) compound represented does not include compound 2,3- dimethyl -5- (trifluoromethyl) -6- (4- (4- (trifluoromethyl) phenoxy group) phenoxy group) quinolyl-4 acetic acid esters and 2,3- dimethyl -7- (trifluoromethyl) -6- (4- (4- (three Methyl fluoride) phenoxy group) phenoxy group) quinolyl-4 acetic acid esters；
2) as R in formula (B) compound represented3For-(C=O) R6, R6For-OR8, R8For C1-4Alkyl, R1For C1-4 Alkyl, R2For C1-4Alkyl, R4cFor hydrogen, when q is 0, Z is not 5- trifluoromethyl -2- pyridyl group or 3- halogen -5- trifluoromethyl -2- Pyridyl group；
Wherein, R1、R2、R3、R4a、R4b、R4c、R5、q、R6、R8There is meaning of the present invention with Z；
Wherein, 2,3- dimethyl -5- (trifluoromethyl) -6- (4- (4- (trifluoromethyl) phenoxy group) phenoxy group) quinoline -4- Structure corresponding to yl acetate are as follows:
2,3- dimethyl -7- (trifluoromethyl) -6- (4- (4- (trifluoromethyl) phenoxy group) phenoxy group) quinolyl-4 acetic acid Structure corresponding to ester are as follows:
Also in some embodiments, the present invention provides one kind compound as shown in formula (C) compound represented or formula (C) Stereoisomer, nitrogen oxides and its acceptable salt:
Condition are as follows: formula (C) compound represented does not include 2,3- dimethyl -5- (trifluoromethyl) -6- ((4'- (trifluoromethyl)-[1,1'- biphenyl] -4- base) oxygroup) quinolyl-4 acetic acid esters and 2,3- dimethyl -7- (trifluoromethyl) -6- ((4'- (trifluoromethyl)-[1,1'- biphenyl] -4- base) oxygroup) quinolyl-4 acetic acid esters；
Wherein, R1、R2、R3、R4a、R4b、R4c、R5, q and Z there is meaning of the present invention；
Wherein, 2,3- dimethyl -5- (trifluoromethyl) -6- ((4'- (trifluoromethyl)-[1,1'- biphenyl] -4- base) oxygroup) Structure corresponding to quinolyl-4 acetic acid esters are as follows:
2,3- dimethyl -7- (trifluoromethyl) -6- ((4'- (trifluoromethyl)-[1,1'- biphenyl] -4- base) oxygroup) quinoline - Structure corresponding to 4- yl acetate are as follows:
Also in further embodiments, the present invention provides with the compound of one of flowering structure or has following structure compound Stereoisomer, nitrogen oxides and its acceptable salt, but be not limited to these compounds:
On the other hand, the present invention provides a kind of composition, and it includes the compound of the present invention as active material.
In some embodiments, it is living to further include acceptable surface in Pesticide Science for composition of the present invention Property agent and carrier.
Also in some embodiments, composition of the present invention includes other active materials, wherein other active matters Matter is fungicide, bactericide, insecticide, acaricide, nematicide, arthropodicides, herbicide or plant growth regulating One of agent is a variety of.
On the other hand, the present invention provides application of the composition comprising the compounds of this invention in agricultural.
In some embodiments, the present invention provides the composition comprising the compounds of this invention and is used as fungicide in agricultural Purposes.
Also in other embodiments, composition of the present invention offer comprising the compounds of this invention is used as in agricultural kills The purposes of worm agent.
Also in some embodiments, the present invention provides composition the answering in other field comprising the compounds of this invention With.
On the other hand, the present invention provides a kind of method of prevention and treatment plant pathogenic fungi, pest, and the method includes with having The compounds of this invention processing plant of effect amount or soil.
Detailed description of the invention
Definition and general terms
Unless otherwise stated, all scientific and technical terminologies used in the present invention have with those skilled in the art of the invention's It is generally understood identical meaning.All patents of the present invention and public publication are integrally incorporated this hair by reference It is bright.
Unless otherwise stated, following definition used herein should be applied.For purposes of the present invention, chemical element with The periodic table of elements CAS editions, and " Handbook of Chemistry and Physics ", the 75th edition, 1994 is consistent.In addition, organic chemistry General Principle can join It examines " Organic Chemistry ", Thomas Sorrell, University Science Books, Sausalito:1999, With " March's Advanced Organic Chemistry " by Michael B.Smith and Jerry March, John Description in Wiley&Sons, New York:2007, entire contents are incorporated herein by reference.
Term " optional " or " optionally " refer to the event then described or situation can with but not necessarily occur, that is, this is retouched It states and includes the case where the case where wherein event or situation occur and do not occur.For example, " optionally by 1,2,3 or 4 ... It is replaced " include the case where replaced group substituent group described in 1 or 2 or 3 or 4 and the group not The case where being replaced by the substituent group.Further, when the group is replaced by 1 substituent group described above, the substituent group Between be mutually indepedent, that is, 1 or more the substituent group can be mutually different, be also possible to identical.
As described in the invention, the compound of the present invention can be optionally replaced one or more substituent groups, such as General formula compound above, or as example special inside embodiment, subclass, and a kind of compound that the present invention is included. In general, term " substitution " indicates one or more hydrogen atoms in given structure replaced specific substituent group.Unless its He shows that an optional substituent group can replace at various substitutable position of that group at aspect.When given knot More than one position can be replaced one or more substituent groups selected from specific group, then substituent group can be identical in structure formula Or differently replace at various locations.
In addition, it is necessary to explanation, unless otherwise explicitly point out, in the present invention used by describing mode " each ... independently be " and " ... be each independently " and " ... independently be " can be interchanged, and shall be understood in a broad sense, both may be used To refer among the different groups, does not influence mutually, can also indicate in phase between expressed specific option between the same symbol In same group, do not influenced mutually between expressed specific option between the same symbol.
It is disclosed in the substituent group of each section of this specification, disclosed compound of present invention according to radical species or range.It is special It does not point out, the present invention includes each independent sub-combinations thereof of each member of these radical species and range.For example, term “C1-6Alkyl " refers in particular to the methyl being individually disclosed, ethyl, C3Alkyl, C4Alkyl, C5Alkyl and C6Alkyl."C1-4Alkyl " refers in particular to Methyl, ethyl, the C being individually disclosed3Alkyl (i.e. propyl, including n-propyl and isopropyl), C4Alkyl (i.e. butyl, including positive fourth Base, isobutyl group, sec-butyl and tert-butyl).
Terminology used in the present invention " alkyl " or " alkyl group " are indicated containing 1 to 20 carbon atom, the straight chain of saturation Or branch univalent hydrocarbyl group, wherein the alkyl group can be optionally by one or more substitutions described in the invention Replaced base.Unless otherwise detailed instructions, alkyl group contains 1-20 carbon atom.In some embodiments, alkyl group Contain 1-12 carbon atom；In other embodiments, alkyl group contains 1-6 carbon atom；In other embodiment In, alkyl group contains 1-4 carbon atom；In other embodiments, alkyl group contains 1-3 carbon atom.Term “C1-6Alkyl " indicates the alkyl group comprising 1-6 carbon atom.
The example of alkyl group includes, but is not limited to, methyl (Me ,-CH3), ethyl (Et ,-CH2CH3), n-propyl (n- Pr、-CH2CH2CH3), isopropyl (i-Pr ,-CH (CH3)2), normal-butyl (n-Bu ,-CH2CH2CH2CH3), isobutyl group (i-Bu ,- CH2CH(CH3)2), sec-butyl (s-Bu ,-CH (CH3)CH2CH3), tert-butyl (t-Bu ,-C (CH3)3), n-pentyl (- CH2CH2CH2CH2CH3), 2- amyl (- CH (CH3)CH2CH2CH3), 3- amyl (- CH (CH2CH3)2), 2- methyl -2- butyl (- C (CH3)2CH2CH3), 3- methyl -2- butyl (- CH (CH3)CH(CH3)2), 3- methyl-1-butyl (- CH2CH2CH(CH3)2), 2- first Base -1- butyl (- CH2CH(CH3)CH2CH3), n-hexyl (- CH2CH2CH2CH2CH2CH3), 2- hexyl (- CH (CH3) CH2CH2CH2CH3), 3- hexyl (- CH (CH2CH3)(CH2CH2CH3)), 2- methyl -2- amyl (- C (CH3)2CH2CH2CH3), 3- first Base -2- amyl (- CH (CH3)CH(CH3)CH2CH3), 4- methyl -2- amyl (- CH (CH3)CH2CH(CH3)2), 3- methyl -3- penta Base (- C (CH3)(CH2CH3)2), 2- methyl -3- amyl (- CH (CH2CH3)CH(CH3)2), 2,3- dimethyl -2- butyl (- C (CH3)2CH(CH3)2), 3,3- dimethyl -2- butyl (- CH (CH3)C(CH3)3), n-heptyl, n-octyl, etc..
Term " alkylidene " expression removes the two of two obtained saturations of hydrogen atom from the linear chain or branched chain hydrocarbon of saturation Valency alkyl group.Unless otherwise detailed instructions, alkylidene group contains 1-12 carbon atom.In one embodiment, alkylidene Group contains 1-8 carbon atom；In one embodiment, alkylidene group contains 1-6 carbon atom；In another embodiment In, alkylidene group contains 1-4 carbon atom；In yet another embodiment, alkylidene group contains 1-3 carbon atom；Also exist In one embodiment, alkylidene group contains 1-2 carbon atom.Such example includes methylene (- CH2), ethylidene (- CH2CH2), propylidene (- CH2CH2CH2) ,-CH (CH3)CH2,-C (CH3)2,-CH2CH2CH(CH3)-,-CH2CH2C (CH3)2, etc..
Term " alkenyl " indicates the linear chain or branched chain monovalent hydrocarbon containing 2-12 carbon atom, wherein at least one carbon- Carbon sp2Double bond, wherein the alkenyl group can optionally replaced one or more substituent groups described in the invention, It includes the positioning of " cis " and " tans ", or the positioning of " E " and " Z ".In some embodiments, alkenyl group includes 2-8 A carbon atom；In other embodiments, alkenyl group includes 2-6 carbon atom；In other embodiment, alkenyl base Group includes 2-4 carbon atom.The example of alkenyl group includes, but is not limited to, vinyl (- CH=CH2), allyl (- CH2CH =CH2), allyl (- CH=CHCH3) etc..
Term " alkynyl " indicates the linear chain or branched chain monovalent hydrocarbon containing 2-12 carbon atom, wherein at least one carbon- Tri- key of carbon sp, wherein the alkynyl group can be optionally replaced one or more substituent groups described in the invention.In In some embodiments, alkynyl group includes 2-8 carbon atom；In other embodiments, alkynyl group includes 2-6 carbon Atom；In other embodiment, alkynyl group includes 2-4 carbon atom.The example of alkynyl group includes, but and unlimited In acetenyl, propinyl etc..
Term " naphthenic base " refers to containing 3-12 ring carbon atom, the nonaromatic saturation monocycle of unit price or multivalence, Bicyclic or three-ring system.In some embodiments, naphthenic base includes 3-10 ring carbon atom；In other embodiments, Naphthenic base includes 3-8 ring carbon atom；In other embodiment, naphthenic base includes 3-6 ring carbon atom.Group of naphthene base Example include, but is not limited to, cyclopropyl, cyclobutyl, cyclopenta, cyclohexyl etc..The group of naphthene base is optional Replaced one or more substituent groups described in the invention.
Term " aryl " indicates a containing 6-14 annular atom or 6-12 annular atom or 8-12 annular atom or 6-10 The monocycle of annular atom, bicyclic and tricyclic aryl group, wherein having one or more attachment points and molecule in the aroma system Rest part be connected, term " aryl " can be used interchangeably with term " aromatic rings " or " aromatic ring ", and the aryl group includes Aromatic rings and aromatic rings or aromatic rings and it is nonaromatic it is carbocyclic fused made of ring system.The example of aryl group can wrap Include phenyl, naphthalene, anthryl, 1,2,3,4- tetralyl, 2,3- dihydro -1H- indenyl, two rings [4,2,0] octyl- 1 (6), 2,4- tri- Alkenyl.The aryl group can be substituted or non-substituted, and wherein substituent group can be, but be not limited to, fluorine, chlorine, bromine, oxygen Generation (=O), cyano, nitro, carboxyl, hydroxyl, amino, amino methyl, aminoacyl, methylamino, phenylamino, hydroxymethyl, first Base sulfonyl, amino-sulfonyl, acetyl group, methoxyl group, phenoxy group, trifluoromethoxy, methyl, ethyl, propyl, isopropyl, just Butyl, tert-butyl, cyclopropyl, cyclopenta, cyclohexyl, tetrahydrofuran base, tetrahydro-thienyl, nafoxidine base, imidazole radicals, imidazoles Quinoline base, piperidyl, piperazinyl, morpholinyl, thienyl, thiazolyl, furyl, pyrrole radicals, phenyl, pyridyl group, pyrimidine radicals ,-C (=NH) NH2Or trifluoromethyl etc..
Term " heterocycle " and " heterocycle " are used interchangeably here, all refer to the saturation comprising 3-12 annular atom or portion Divide unsaturated monocyclic, bicyclic or tricyclic system, wherein at least one annular atom is selected from nitrogen, sulphur and oxygen atom, and the heterocycle Any one ring is all nonaromatic in system.Unless otherwise stated, heterocycle can be carbon-based or nitrogen base, and-CH2Base Group can optionally be substituted by-C (=O)-.The sulphur atom of ring can optionally be oxidized to S- oxide.The nitrogen-atoms of ring can To be optionally oxidized to N- oxygen compound.In some embodiments, heterocycle is 5-12 former molecular heterocycle；In In other embodiments, heterocycle is 5-8 former molecular heterocycle；In other embodiment, heterocycle 5-7 A molecular heterocycle of original；Also in some embodiments, heterocycle is 5-6 former molecular heterocycle.Heterocycle is also It can be bicyclic heterocyclic radical；In some embodiments, heterocycle is 7-12 former molecular bicyclic heterocyclic radical；At other In embodiment, heterocycle is 7-10 former molecular bicyclic heterocyclic radical；In other embodiment, heterocycle is 8-10 A molecular bicyclic heterocyclic radical of original.
The example of heterocycle includes, but are not limited to: Oxyranyle, azelidinyl, oxetanylmethoxy, pyrrolidinyl, Pyrazolidinyl, dihydrothiophene, 1,3- dioxy cyclopenta, 1,3- dioxocyclohex base, 1,4- dioxocyclohex base, two sulphur cyclopenta, THP trtrahydropyranyl, tetrahydro thiapyran base, piperidyl, 1,2- dihydropyridine base, morpholinyl, thio-morpholinyl, hexahydropyrimidine base, 1,6- Dihydro-pyrimidin base, 1,2- dihydro-pyrimidin base, 1,2- dihydro pyrazine base, 1,3- oxazines alkyl, piperazinyl, oxazolidinyl, dioxanes Base, dithianyl, thiophene oxane base, high piperazine base, homopiperidinyl, oxepane alkyl, thia cycloheptyl alkyl, 2- oxa- -5- nitrogen Miscellaneous bicyclic [2.2.1] hept- 5- base.- CH in heterocycle2Group includes, but are not limited to 2- oxygen by-C (=the O)-example replaced For pyrrolidin-1-yl, oxo -1,3- thiazolidinyl, 2- oxo oxazolidine -3- base, 2- oxo-piperidine -1- base, 3- oxomorpholin Base, 2- oxypiperazin -1- base, 3,5- dioxy piperazine piperidinyl, -1 (2H)-base of 2- oxo tetrahydropyrimidine and 2- oxo-dihydro pyrimidine -1 (2H)-base.The example that sulphur atom is oxidized in heterocycle includes, but are not limited to sulfolane base, 1,1- dioxothiomorpholinyl With 1,1- dioxo -1,2- thio-morpholinyl.The heterocyclyl groups can be substituted or non-substituted, and wherein substituent group can It to be, but is not limited to, fluorine, chlorine, bromine, oxo (=O), cyano, nitro, carboxyl, hydroxyl, amino, amino methyl, aminoacyl Base, methylamino, phenylamino, hydroxymethyl, methyl sulphonyl, amino-sulfonyl, acetyl group, methoxyl group, phenoxy group, trifluoro methoxy Base, methyl, ethyl, propyl, isopropyl, normal-butyl, tert-butyl, cyclopropyl, cyclopenta, cyclohexyl, tetrahydrofuran base, tetrahydro thiophene Pheno base, nafoxidine base, imidazole radicals, imidazolinyl, piperidyl, piperazinyl, morpholinyl, thienyl, thiazolyl, furyl, pyrrole Cough up base, phenyl, pyridyl group, pyrimidine radicals ,-C (=NH) NH2Or trifluoromethyl etc..
In some embodiments, heterocycle is the 5-6 molecular heterocycle of original, is referred to comprising 5 or 6 annular atoms Saturation or the unsaturated monocycle in part, wherein at least one annular atom are selected from nitrogen, sulphur and oxygen atom.5-6 former molecular miscellaneous The example of ring group includes, but are not limited to: pyrrolidinyl, pyrrolinyl, pyrazolinyl, pyrazolidinyl, imidazolinyl, imidazolidine Base, tetrahydrofuran base, dihydrofuryl, tetrahydro-thienyl, oxazolidinyl, piperidyl, 1,2- dihydropyridine base, morpholinyl, sulphur For morpholinyl, hexahydropyrimidine base, 1,6- dihydro-pyrimidin base, 1,2- dihydro-pyrimidin base, 1,2- dihydro pyrazine base, 1,3- oxazines alkane Base, piperazinyl, 1,2,3,6- tetrahydro pyridyl, 1,2,3,4- tetrahydro pyridyl, 1,2,3,4- tetrahydro-pyrimidine base, 2,5- dihydros- 1H- pyrrole radicals etc..- CH in 5-6 former molecular heterocycle2Group can be replaced by-C (=O)-, or in which sulphur it is former Son can be oxidized to S- oxide.Also, described 5-6 former molecular heterocyclyl groups can optionally by one or Replaced multiple substituent groups described in the invention.
Monocycle of term " heteroaryl " expression containing 5-12 annular atom or 5-10 annular atom or 5-6 annular atom, Bicyclic and three-ring system, wherein at least one ring are aromatic, and at least one ring includes one or more nitrogen, sulphur and oxygen Hetero atom, wherein thering are one or more attachment points to be connected with molecule rest part in the heteroaryl system.Term " heteroaryl " can To be used interchangeably with term " hetero-aromatic ring " or " heteroaromatics ".The heteroaryl includes hetero-aromatic ring and aromatic rings, hetero-aromatic ring With hetero-aromatic ring or hetero-aromatic ring and nonaromatic carbocyclic ring or it is heterocyclic fused made of ring system.In some embodiments, 5-10 A molecular heteroaryl of original includes 1,2,3 or 4 hetero atom for being independently selected from oxygen, sulphur and nitrogen.In some embodiments, miscellaneous Aryl is 7-12 former molecular heteroaryl, and it includes the hetero atoms that 1,2,3 or 4 is independently selected from O, S and N；7-12 former Molecular heteroaryl can be single ring systems, be also possible to the bicyclic system comprising two rings.In other embodiments, Heteroaryl is 7-10 former molecular heteroaryl, and it includes the hetero atoms that 1,2,3 or 4 is independently selected from oxygen, sulphur and nitrogen；7-10 A molecular heteroaryl of original can be single ring systems, be also possible to the bicyclic system comprising two rings.The heteroaryl groups It can be substituted or non-substituted, wherein substituent group can be, but be not limited to, fluorine, chlorine, bromine, oxo (=O), cyano, nitre Base, carboxyl, hydroxyl, amino, amino methyl, aminoacyl, methylamino, phenylamino, hydroxymethyl, methyl sulphonyl, amino sulphur Acyl group, acetyl group, methoxyl group, phenoxy group, trifluoromethoxy, methyl, ethyl, propyl, isopropyl, normal-butyl, tert-butyl, cyclopropyl Base, cyclopenta, cyclohexyl, tetrahydrofuran base, tetrahydro-thienyl, nafoxidine base, imidazole radicals, imidazolinyl, piperidyl, piperazine Base, morpholinyl, thienyl, thiazolyl, furyl, pyrrole radicals, phenyl, pyridyl group, pyrimidine radicals, guanidine radicals (- NHC (=NH) NH2) ,-N=C=S ,-C (=NH) NH2Or trifluoromethyl etc..
The example of heteroaryl groups includes, but is not limited to, furyl, imidazole radicals (such as 1H- imidazoles -1- base), isoxazole Base, oxazolyl (such as 2- oxazolyl), pyrrole radicals, 1,3,4- oxadiazoles base, 2- pyridyl group, 3- pyridyl group, 4- pyridyl group, 2- pyrimidine Base, 4- pyrimidine radicals, 5- pyrimidine radicals, pyridazinyl (such as 3- pyridazinyl), thiazolyl (such as 2- thiazolyl), 2- thienyl, 3- thienyl, Pyrazolyl (such as 4- pyrazolyl, 1H- pyrazol-1-yl), pyrazinyl, cyanuro 1,3,5, triazolyl, tetrazole radical；Also include with Under it is bicyclic, but it is bicyclic to be not limited to these: benzopyrrole base, 6,7- dihydro-thiophene [3,2-c] and pyridine -5 (4H)-base, 1, 3- dioxoisoindolin -2- base, pyrimido imidazole radicals, benzimidazolyl, benzofuranyl, dihydro benzo furyl, benzo Thienyl, indyl (such as 1H- indoles -1- base), isoindoline -2- base, benzo [d] thiazol-2-yl, indazolyl (such as 1H- Yin Azoles -1- base etc.), quinolyl (such as 2- quinolyl, 3- quinolyl, 4- quinolyl), isoquinolyl (such as 1- isoquinolyl, 3- isoquinoline Quinoline base or 4- isoquinolyl), 5,6,7,8- tetrahydric quinoline group, 3,4- dihydro -2H- pyrans simultaneously [3,2-b] pyridyl group, 2,3- bis- Hydrogen-[1,4] dioxin simultaneously [2,3-b] pyridyl group, 2,3- dihydrobenzo [b] [1,4] dioxin base, 6,7- dihydro -5H- pentamethylene And [3,2-b] pyridyl group, 2,3 dihydro furan [3,2-b] pyridine, quinoline ketone group, dihydroquinoline ketone group, benzo [d] [1,3] two Penta ring -5- base of oxa- etc..
Term " alkoxy " indicates that alkyl group is connected by oxygen atom with molecule rest part, wherein alkyl group tool There is meaning as described in the present invention.In some embodiments, alkoxy base contains 1-6 carbon atom；In other implementations In scheme, alkoxy base contains 1-4 carbon atom；In other embodiment, it is former that alkoxy base contains 1-3 carbon Son.The alkoxy base can be optionally replaced one or more substituent groups described in the invention.Alkoxy base Example include, but is not limited to, methoxyl group (MeO ,-OCH3), ethyoxyl (EtO ,-OCH2CH3), 1- propoxyl group (n-PrO, n- Propoxyl group ,-OCH2CH2CH3), etc..
Term " aryloxy " indicates that aryl group is connected by oxygen atom with molecule rest part, wherein aryl group With meaning as described in the present invention.
Term " aryl-alkylidene " indicates that aryl group is connected by alkylidene with molecule rest part, wherein aryl base Group and alkylidene group have meaning as described in the present invention.Aryl-the alkylidene group can be optionally by one or more Replaced a substituent group described in the invention.Aryl-alkylidene example includes, but is not limited to, phenylmethylene, phenyl Ethylidene etc..
Term " hetero atom " refers to O, S, N, P and Si, the form including any oxidation state of N, S and P；Primary, secondary, tertiary amine and season The form of ammonium salt；Or the substituted form of hydrogen in heterocycle on nitrogen-atoms, for example, N is (as in 3,4- dihydro-2 h-pyrrole base N), NH (as the NH in pyrrolidinyl) or NR (NR in pyrrolidinyl replaced as N-).
Term " halogen " refers to fluorine (F), chlorine (Cl), bromine (Br) or iodine (I).
Term " halogenated alkyl ", " halogenated alkenyl ", " halo alkynyl ", " halogenated alkoxy ", " halogenated aryl " or " halogenated miscellaneous Aryl ", indicate alkyl, alkenyl, alkynyl, alkoxy, aryl or heteroaryl group replaced one or more halogen atoms, In, alkyl, alkenyl, alkynyl, alkoxy, aryl or heteroaryl group is with meaning as described in the present invention.
" acceptable salt " of the invention includes the salt of sour addition and the salt of alkali addition, and suitable alkali is alkali metal and alkaline earth gold The hydroxide of category, carbonate, bicarbonate, especially sodium, potassium, magnesium and calcium salt and ammonium, there is (C1-C4)-alkyl base The primary, secondary and tertiary amine of group, (C1-C4Mono-, two- and tri-alkanolamine, choline and the choline chloride of)-alkanol.
Salt can be a kind of salt with inorganic acid addition, and inorganic acid can be hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid or phosphoric acid, Or the salt with organic acid addition, organic acid can be formic acid, carbonic acid and alkanoic acid such as acetic acid, trifluoroacetic acid, trichloroacetic acid and third Acid and glycolic, thiocyanic acid, lactic acid, succinic acid, citric acid, benzoic acid, cinnamic acid, oxalic acid, saturation or single insatiable hunger and/or two Unsaturated C6-C20Fatty acid, alkylsurfuric acid monoesters, alkyl sulfonic acid be (linear or branched alkyl group with 1-20 carbon atom Sulfonic acid), aryl sulfonic acid or aryl disulfonic (aromatic group with one or two sulfonic acid group, such as phenyl and naphthalene), Alkyl phosphonic acid (phosphonic acids of the linear or branched alkyl group with 1-20 carbon atom), arylphosphonic acid or aryl di 2 ethylhexyl phosphonic acid (have one A or two phosphonyl groups aromatic group, such as phenyl and naphthalene), wherein the alkyl and aryl group can take with other Dai Ji, such as p-methyl benzenesulfonic acid, salicylic acid, PAS, 2- phenoxy benzoic acid, Aspirin etc..
The composition and preparation of the compounds of this invention
The invention further relates to the compositions comprising a kind of the compounds of this invention formula (A).This kind of composition is especially further wrapped Containing auxiliary agent as defined below.
Suitable auxiliary agent is solvent, liquid-carrier, solid carrier or filler, surfactant, dispersing agent, emulsifier, profit Humectant, adjuvant, solubilizer, penetration enhancer, protective colloid, adhesive, thickener, moisturizer, expellent, attractant, Feeding stimulants, compatilizer, fungicide, antifreezing agent, defoaming agent, colorant, tackifier and adhesive.
Suitable solvent and liquid-carrier are water and organic solvent, arrive high boiling mineral oil fractions as in, such as kerosene, Diesel oil；The oil of plant or animal origin；Aliphatic series, cyclic annular and aromatic hydrocarbons, such as toluene, paraffin, naphthane, alkylated naphthalene；Alcohol Class, such as ethyl alcohol, propyl alcohol, butanol, benzylalcohol, cyclohexanol；Glycols；DMSO；Ketone, such as cyclohexanone；Esters, such as lactate, Carbonic ester, aliphatic ester, gamma-butyrolacton；Fatty acid；Phosphonate ester；Amine；Amides, such as N-Methyl pyrrolidone, fatty acid Dimethylformamide；And their mixture.
Suitable solid carrier or filler are mine soil, such as silicate, silica gel, talcum, kaolin, lime stone, lime, white Chalk, clay, dolomite, diatomite, bentonite, calcium sulfate, magnesium sulfate, magnesia；Polysaccharide, such as cellulose, starch；Fertilizer, Such as ammonium sulfate, ammonium phosphate, ammonium nitrate, ureas；The product of plant origin, such as flour, bark powder, wood powder and shuck powder, And their mixture.
Suitable surfactant is surface reactive material, such as anion, cation, nonionic and amophoteric surface active Agent, block polymer, polyelectrolyte and their mixture.Such surfactant may be used as emulsifier, dispersing agent, Solubilizer, wetting agent, penetration enhancer, protective colloid or adjuvant.
Suitable anionic surfactant be sulfonic acid, sulfuric acid, phosphoric acid, the alkali metal of carboxylic acid, alkaline-earth metal or ammonium salt with And their mixture.The example of sulfonate is alkylaryl sulfonates, diphenyl sulfonate, alpha-alkene sulfonate, lignin sulphur Hydrochlorate, the sulfonate of fatty acid and oil, the sulfonate of ethoxylated alkylphenol, the sulfonate of alkoxylate aryl phenol, condensation naphthalene Sulfonate, the sulfonate of dodecyl-and tridane, the sulfonate of naphthalene and alkylnaphthalene, sulfosuccinate or sulfo group Succinamate.The example of sulfate is the sulfuric acid of the sulfate of fatty acid and oil, the sulfate of ethoxylated alkylphenol, alcohol The sulfate of salt, the sulfate of ethoxylated alcohol or aliphatic ester.Phosphatic example is phosphate ester.The example of carboxylate is Alkyl carboxylate and carboxylation alcohol or alkylphenol ethoxylate.
Suitable nonionic surfactant is alcoxylates, the fatty acid amide that N- replaces, amine oxide, esters, Glycosyl surfactant active, polymeric surfactant and its mixture.The example of alcoxylates is that all 1-50 as has already been work as Measure the compound of alkoxylated alcohol, alkyl phenol, amine, amide, aryl phenol, fatty acid or aliphatic ester.It can be by ethylene oxide And/or propylene oxide is used for alkoxylate, preferably ethylene oxide.The example for the fatty acid amide that N- replaces is fatty acid glucose acyl Amine or Marlamid.The example of esters is aliphatic ester, glyceride or monoglyceride.The reality of glycosyl surfactant active Example is anhydro sorbitol, ethoxylated sorbitan, sucrose and glucose ester or alkyl polyglucoside.Polymer surfactants The example of agent is the homopolymer or copolymer of vinyl pyrrolidone, vinyl alcohol or vinyl acetate.
Suitable cationic surfactant is season type surfactant, such as the quaternary ammonium with 1 or 2 hydrophobic group The salt of compound or long chain primary amines.Suitable amphoteric surfactant is alkyl betaine and imidazolines.Suitable block is poly- It closes A-B the or A-B-A type block polymer that object is the block comprising polyoxyethylene and polyoxypropylene, or includes alkanol, poly- The A-B-C type block polymer of ethylene oxide and polyoxypropylene.Suitable polyelectrolyte is polyacids or polybases.The example of polyacids is The alkali metal salt or polyacids comb-shaped polymer of polyacrylic acid.The example of polybases is polyvinylamine or polyvinylamine.
Suitable adjuvant is that itself have insignificant pesticide activity or in itself even without pesticide activity and improvement Compound of the compound A to the biology performance of object.Example is surfactant, mineral oil or vegetable oil and other are helped Agent.
Suitable thickener is that polysaccharide (such as xanthan gum, carboxymethyl cellulose), inorganic clay are (organically-modified or unmodified ), polycarboxylate and silicate.
Suitable antifreezing agent is ethylene glycol, propylene glycol, urea and glycerol.
Suitable defoaming agent be polysiloxanes, silicone cream, long-chain alcohol, fatty acid and its salt and organic fluorocompound and its Mixture.
Suitable colorant (such as red coloration, blue or green) is low aqueous solubility pigment and water-soluble dye.Example is Inorganic colourant (such as iron oxide, titanium oxide, Hexacyanoferrate iron) and toner (such as alizarin colouring agent, azo Toner and phthalocyanine colorant).
Suitable tackifier or adhesive are polyvinylpyrrolidone, polyvinyl acetate, polyvinyl alcohol, polyacrylic acid Ester, biowax or synthetic wax and cellulose ether.
If appropriate, other additional components, such as protective colloid, adhesive (binder), sticker also may be present (adhesive), thixotroping substance, bleeding agent, stabilizer, chelating agent (sequestrant), complexing agent.In general, it is described activity at Dividing can combine with any solid or liquid additive for being usually used in preparation purpose.
Agrochemicals fungicide of the present invention, insecticide can be applied with its dosage form or use form prepared therefrom With the use form such as aerosol, capsule suspension, harl concentrating agents (cold-fogging concentrate), heat Mist concentrating agents, encapsulated granule, fine grained agent, the mobility concentrating agents (flowable for seed treatment Concentrate), instant solution, can the pulvis of dusting, emulsifiable concentrating agents, oil in water emulsion, water-in-oil emulsion, big Granule, fine granule, oil-dispersing property powder agent, oily compatibility flowing concentrating agents, oily forming ionisable polymer, gas agent are (in pressure Under), produce gas product, foaming agent, paste, suspension concentrating agents, outstanding newborn concentrating agents, soluble concentrating agents, suspension, wettable powder Agent, soluble powder, powders and granules, the granule or tablet of water solubility and water dispersible, for the water-soluble of seed treatment Property or water-dispersible powder, wettable powder, the natural products through active material dipping and synthetic and polymer and kind Microcapsules and ULV (ultra low volume) harl and hot mist preparation in sub- coating material.
The preparation can optionally include the combination containing other agricultural chemical compounds.
Compound of the present invention can combine that form Fungicidal mixture and their collaboration mixed with other fungicides Close object.Fungicidal compounds of the present invention are usually administered in combination with one or more other fungicides, so that prevention and treatment is more The undesirable disease of wide scope.
In addition, compound of the present invention can be in conjunction with other insecticides, including insecticide, nematicide, mite killing Agent, arthropodicides (arthropodicide), fungicide or their combination, other insecticides are with regard to selected by application Medium in it is compatible with the compounds of this invention and not antagonism the compounds of this invention activity to form insecticide mixtures and they Synergistic mixtures.
In addition, compound of the present invention can form biocidal mixtures in conjunction with herbicide and cooperateing with for they is mixed Close object.Compound of the present invention is usually administered in combination with one or more herbicides, to prevent and treat the not phase of wider range Hope plant.
In addition, the agricultural chemical compound can also be bactericide, attractant, growth regulator, fertilizer, safener, Fungicide (sterilant) or their combination, wherein the agricultural chemical compound just application selected medium in this hair Bright compound is compatible and activity of not antagonism the compounds of this invention.Therefore, in said embodiment, by other pesticides Compound is used as supplement toxic agent, for identical or different purposes.
Using the compounds of this invention composition to plant and plant parts carry out processing of the invention can directly carry out or It acts on its ambient enviroment, habitat or memory space by conventional treatment method to carry out, the conventional treatment method is, such as leads to Dipping is crossed, sprinkling, spraying, irrigation, evaporation, dusting, atomizing, broadcasts sowing, foam, smearing, being coated with, watering (pouring), instiling, for Plant propagation material can also pass through dry seed treatment, wet seed treatment, slurries processing, crust, coating especially for seed One or more layers coating etc..It can also be injected by ultra-low volume method or by the compounds of this invention preparation or the compounds of this invention itself Active material is efficiently used into soil.
The application of the compounds of this invention and composition
The present invention relates to control or prevent non-limiting example of the useful plant by the pest encroached on from including:
Semiptera (Hemiptera): plant hopper (Delphacidae (Delphacidae)) such as brown paddy plant hopper (Nilaparvata Lugens), small small brown rice planthopper (Laodelphax striatellus)；Leafhopper (Deltocephalidae (Deltocephalidae)) is such as Green rice leafhopper (rice green leafhopper (Nephotettix cincticeps))；Aphid (Aphidiadae (Aphididae)) such as cotten aphid (Aphis Gossypii), aphis craccivora (Aphis craccivora Koch)；Pentatomiddae (Pentatomidae) such as Nezaraantennata (Nezara antennata)；Aleyrodid (Aleyrodidae) such as greenhouse whitefly (Trialeurodes vaporariorum)；A red-spotted lizard (Coccidae) such as California red scale (Calformia red scale) (Aonidiella aurantii)；Tingidae (Tingidae)；Wood louse (Homoptera, Psyllidea)；
Lepidoptera (Lepidoptera): snout moth (Pyralidae) such as striped rice borer (Chilo suppressalis)；Noctuid (Noctuidae) such as Spodoptera litura (Spodoptera litura), mythimna separata (Pseudaletia separata), real noctuid Belong to (Heliothis spp.) and Helicoverpa (Helicoverpa spp.)；White butterfly (Pieridae) such as cabbage butterfly (Pieris rapae)；Roll up moth (Tortricidae) such as Adoxophyessp (Adoxophyes)；Thin moth (Gracillariidae) such as Caloptiliatheivora (Caloptilia theivora) and the thin moth of apple (Phyllonorycter ringoneella)；Eat into fruit moth (Carposinidae) such as peach fruit moth (Carposina niponensis)；Lyonetid (Lyonetiidae) such as Lyonetiaspp (Lyonetia spp.)；Poison moth (Lymantriidae) such as Euproctis (Lymantria spp.) and Euproctis (Euproctis spp.)；Ermine moth (Yponomeutidae) such as diamondback moth (Plutella xylostella)；Gelechiid (Gelechiidae) such as Pectinophora gossypiella (Pectinophora gossypiella) and potato tuberworm (Phthorimaea operculella)；Moths attracted by lamplight (Arctiidae) such as fall webworms (Hyphantria cunea)；And rain moth (Tineidae) is such as Casemaking clothes moth (Tineatranslucens) and Tineolabisselliella (Tineola bisselliella)；
Thysanoptera (Thysanoptera): Frankliniella occidentalis (Frankliniella occidentalis), palm thrips (Thrips palmi), Scirtothripsdorsalis (Scirtothrips dorsalis), onion thrips (Thrips tabaci), beautiful colored Ji Horse (Frankliniella intonsa) and Frankliniellafusca (Frankliniella fusca)；
Diptera (Diptera): housefly (Musca domestica), Culex pipiens pallens (Culex popiens Pallens), Tabanustrigonus (Tabanus trigonus), onion fly (Hylemya anitqua), delia platura (Hylemya Platura), Anopheles sinensis (Anopheles sinensis), Japanese rice maggot (Agromyza oryzae), rice leafminer (Hydrellia griseola), ricestem-fly (Chlorops oryzae), melon widow's hair on the neck trypetid (Dacus cucurbitae), Middle sea fruit fly (Ceratitis capitata) and Liriomyza trifolii (Liriomyza trifolii)；
Coleoptera (Coleoptera): ladybug of eggplant 28 stars (Epilachna vigintioctopunctata), Huang Qu Dish flea beetle (Phyllotreta striolata), Oulema oryzae (Oulema oryzae), Echinocnemussquameus (Echinocnemus Squameus), Lissorhoptrusoryzophilus (Lissorhoptrus oryzophilus), Anthonomusgrandis (Anthonomus grandis), Callosobruchus chinensis (Callosobruchus chinensis), Sphenophorusvenatus (Sphenophorus venatus), Japan popillia flavosellata fairmaire (Popillia japonica), Anomalacuprea (Anomala cuprea), Diabroticaspp (Diabrotica spp.), Colorado potato beetles (Leptinotarsa decemlineata), click beetle category (Agriotes spp.), tobacco death watch beetle (Lasioderma serricorne), Anthrenus verbasci (Anthrenus verbasci), red flour beetle (Tribolium Castaneum), Lyctus brunneus Stephens (Lyctus brunneus), Anoplophoramalasiaca (Anoplophora malasiaca) and vertical hole are cut Tip bark beetle (Tomicus piniperda)；
Orthoptera (Orthoptera): Asiatic migrotory locust (Locusta migratoria), African mole cricket (Gryllotalpa Afficana), Oxyayezoensis (Oxya yezoensis) and O. japonica (Oxya japanica)；
Hymenoptera (Hymenoptera): Athaliarosae (Athalia rosae), Myrmecina (Acromyrmex ) and Solenopsis (Solenopsis spp.) spp.；
Nematode (Nematodes): aphelenchoides besseyi (Aphelenchoides besseyi), Nothotylenchusacris (Nothotylenchus acris), soy bean cyst roundworm (Heterodera glycines), Meloidogyne incognita (Meloidogyne incognita), Pratylenchus (Pratylenchus penetrans) and Nacobbusaberrans (Nacobbus aberrans)；
Blattaria (Blattariae): Groton bug (Blattella germanica), Peroplaneta fluligginosa (Periplaneta Fuliginosa), American cockroach (Periplaneta Americana), Periplanetabrunnea (Periplaneta brunnea) and east Square blattaria (Blatta orientalis)；
Acarina (Acarina): Tetranychidae (Tetranychidae) is (for example, Tetranychus cinnabarinus (Tetranychus Cinnabarinus), Tetranychus urticae (Tetranychusurticae), panonychus citri (Panonychus citri) and unguiculus Mite category (Oligonychus spp.))；Eriophyidae (Eriophyidae) is (for example, Aculopspelekassi (Aculops pelekassi))；Tarsonemidae (Tarsonemidae)；Tenuipalpidae (Tenuipalpidae)；Tuckerellidae (Tuckerellidae)；Tyroglyphidae (Tuckerellidae Acaridae)；Pyroglyphidae (Pyroglyphidae) (for example, Dust mite (Dermatophagoides farinae) and dermatophagoides pteronyssinus (Dermatophagoides ptrenyssnus))；It is carnivorous Mite section (Cheyletidae), Cheyletusmoorei (Cheyletus malaccensis) and Cheyletusmoorei (Cheyletus moorei)；And Dermanyssidae (Dermanyssidae).
The compound of the present invention and composition, which have, potentially kills microbial activity, can in crop protection and material protection For preventing and treating unwanted microorganism, such as fungi and bacterium, to Plasmodiophoromycetes (Plasmodiophoromycetes), Peronosporomycetes (synonym Oomycete (Oomycetes)), Chytridiomycetes (Chytridiomycetes), Zygomycetes (Zygomycetes), Ascomycetes (Ascomycetes), Basidiomycetes (Basidiomycetes) and deuteromycetes (Deuteromycetes) soil-borne fungus of (synonym Fungi imperfecti (Fungiimperfecti)) has effect.It can make It is blade face fungicide, seed dressing fungicide and soil fungicide in crop protection.
Within the scope of the invention, useful plant includes following floristics: cereal (wheat, barley, rye, oat, Rice, corn, sorghum and relative species)；Beet (preserved carrot and fodder beet)；The operatic circle, drupe and soft water fruit (apple, Pears, plum, peach, almond, cherry, strawberry, raspberry and blackberry, blueberry)；Leguminous plant (hyacinth bean, guest's beans, pea, soybean)；Oil plant is made Object (rape, leaf mustard, olive, sunflower, coconut, castor oil plant, cocoa bean, peanut or soybean)；Mellon plant (pumpkin, Cucumber, muskmelon)；Fibre plant (cotton, flax, hemp, jute)；Citrus fruit (orange, lemon, grape fruit, citrus)；Vegetable Dish (spinach, lettuce, asparagus, wild cabbage, carrot, onion, tomato, potato, hot red pepper)；Laurel class plant (avocado, Cinnamomum, camphor tree Brain) or plant, such as tobacco, nut, coffee, eggplant, sugarcane, tea, pepper, grapevine, hops, banana and natural rubber Plant, together with turf, ornamental and forest plants, such as flowers, shrub, broad leaf tree or evergreen tree, such as coniferous tree and plant Propagation material.
Term " plant propagation material " should be understood as indicating the reproductive part of the plant, such as seed, these parts It can be used for the breeding and nutritive material of the plant, such as cutting or stem tuber (such as potato).
Fungicide and insecticide composition of the invention passes through a effective amount of active material treatability or protectiveness/pre- Anti- property prevention and treatment plant pathogenic fungi and pest.Therefore, the invention further relates to for preventing and treating plant pathogenic fungi and pest is controlled The property treated and protectiveness method, the method is by being applied to seed, plant or plant for active constituent or composition of the invention The soil at position, fruit or plant growth carries out.Application can be in seed, plant or plant parts, fruit or plant growth Soil is carried out before and after pathogenic epiphyte and pestinfestation.
Term " effective quantity " used indicates to be enough on cultivated plant or prevent and treat in material protection harmful fungoid and pest And do not cause the present composition or compound for the amount significantly damaged to plant processed.The amount can change in a wide range And depend on various factors fungi and pest species such as to be prevented and treated, processed cultivated plant or material, weather conditions and Particular compound used.
The compounds of this invention or composition application method are simple, and the compounds of this invention or composition are imposed on to the disease On bacterium, pest or its somatomedin.When the administration dosage of the compounds of this invention or composition is according to weather condition, dosage form, application The variation such as machine, method of administration, administration area, target disease, target crop.
General synthesis process
In the present specification, if there are any difference between chemical name and chemical structure, structure is dominant.Generally Ground, the compound of the present invention described method can be prepared through the invention, unless there are further instruction, wherein taking The definition of Dai Ji is such as shown in (A).Following synthetic schemes and embodiment 1-43 is for being further illustrated the contents of the present invention.
Those skilled in the art will realize that: chemical reaction described in the invention can be used to suitably prepare perhaps Other compounds mostly of the invention, and other methods for the preparation of the compounds of the present invention are considered as in model of the invention Within enclosing.For example, the synthesis of the compound of those non-illustrations can be successfully by those skilled in the art according to the present invention It is completed by method of modifying, such as protection interference group appropriate, by utilizing other known reagent (in addition to described in the invention ), or reaction condition is made into some conventional modifications.In addition, reaction disclosed in this invention or known reaction condition are also public It is suitable for the preparation of other compounds of the invention with recognizing.
Chromatographic column is using silicagel column.Silica gel (300-400 mesh) is purchased from Haiyang Chemical Plant, Qingdao.Spectroscopic data of the nuclear magnetic resonance It is measured by Bruker Avance400 nuclear magnetic resonance spectrometer or 600 nuclear magnetic resonance spectrometer of Bruker Avance III HD, With CDC13,DMSO-d6,CD3OD or acetone-d6It (is reported as unit of ppm) for solvent, with TMS (0ppm) or chloroform (7.25ppm) is used as reference standard.When there is multiplet, following abbreviation: s (singlet, unimodal), d will be used (doublet, bimodal), t (triplet, triplet), m (multiplet, multiplet), br (broadened, broad peak), dd (doublet of doublets, quartet), dt (doublet of triplets, double triplets), ddd (doublet of Doublet of doublets, in pairs doublet), and ddt (doublet of doublet of triplets, it is triple in pairs Peak), dddd (doublet of doublet of doublet of doublets, in pairs double doublet).Coupling constant is used Hertz (Hz) indicates.
The condition of low resolution mass spectrometry (MS) data determination is: Agilent 6120Quadrupole HPLC-MS (pillar Model: Zorbax SB-C18,2.1x 30mm, 3.5 μm, 6min, flow velocity 0.6mL/min, mobile phase: 5%-95% (contains The CH of 0.1% formic acid3CN) in (H containing 0.1% formic acid2O the ratio in))), it is detected in 210/254nm with UV, with electron spray electricity From mode (ESI).
The use of logogram word below is through the present invention:
PE petroleum ether
EA ethyl acetate
DMF N,N-dimethylformamide
CDC13Deuterated chloroform
G grams
Mg milligrams
Mol moles
Mmol mMs
ML milliliters
Following reaction scheme describes the step of preparation disclosed compound of present invention.Wherein, R1、R2、R3、R4a、R4b、R4c、 R5、R6、R8、Rm、Rn, q and Z there is meaning described in the invention.
Synthetic schemes
Synthetic schemes (one)
Formula (A-1) compound represented can be synthesized by method disclosed in synthetic schemes (one).Compound a and chemical combination Object b reacts in alkaline system, obtains compound c；Compound c passes through reduction reaction, obtains compound d；Compound d is through overweight The compound obtained after nitridation reaction obtains compound e by esterification；Compound e passes through hydrolysis, obtains chemical combination Object f；Compound f reacts in alkaline system with compound g, obtains compound h；Compound h obtains chemical combination by reduction reaction Object i；The compound that compound i is reacted with compound j heats reaction in diphenyl ether system, obtains compound k；Chemical combination Object k is reacted with compound l, obtains compound A-1；
Wherein X is fluorine, chlorine or bromine.
Synthetic schemes (two)
Formula (A-2) compound represented can be synthesized by method disclosed in synthetic schemes (two).Compound m and chemical combination Object g reacts in alkaline system, obtains compound n；Compound n passes through reduction reaction, obtains compound o；Compound o and chemical combination The compound obtained after object j reaction, reaction is heated in diphenyl ether system, obtains compound p；Compound p and compound l are anti- It answers, obtains compound A-2；
Wherein X is fluorine, chlorine or bromine.
Synthetic schemes (three)
Formula (A-3) compound represented can be synthesized by method disclosed in synthetic schemes (three).Compound p and chemical combination Object q reacts in alkaline system, obtains compound A-3；
Wherein X is fluorine, chlorine or bromine.
Synthetic schemes (four)
Formula (A-4) compound represented can be synthesized by method disclosed in synthetic schemes (four).Compound p and chemical combination Object r reacts in alkaline system, obtains compound A-4.
Synthetic schemes (five)
Formula (A-5) compound represented can be synthesized by method disclosed in synthetic schemes (five).Compound p and chemical combination Object s reacts in alkaline system, obtains compound A-5.
Synthetic schemes (six)
Formula (A-6) compound represented can be synthesized by method disclosed in synthetic schemes (five).Compound p and chemical combination Object t reacts in alkaline system, obtains compound A-6.
Synthetic schemes (seven)
Formula (A-7) compound represented can be synthesized by method disclosed in synthetic schemes (seven).Compound u and chemical combination Object g reacts in alkaline system, obtains compound v；Compound v passes through reduction reaction, obtains compound w；Compound w and chemical combination The compound that object j reacts heats reaction in diphenyl ether system, obtains compound x；Compound x is reacted with compound y, Obtain compound A-7；
Wherein X is fluorine, chlorine or bromine；
Wherein RzFor
Specific embodiment
The following examples are used to illustrate the present invention, but are not intended to limit the scope of the present invention..
Embodiment
In the examples below, the compounds of this invention is described in detail by taking part of compounds of the invention as an example in inventor Preparation process.
Intermediate: the synthesis of 4- (4- bromobenzene oxygroup) phenol
Step 1: the synthesis of 1- bromo- 4- (4-nitrophenoxy) phenyl
By 4- bromophenol (8.6g, 50mmol), potassium carbonate (10.4g, 75mmol), N,N-dimethylformamide (100mL) It is added in 500mL single port bottle, and reaction is warming up at 60 DEG C and is stirred 2 hours.Then p-fluoronitrobenzene is slowly added dropwise The n,N-Dimethylformamide solution (30mL) of (7.1g, 50mmol) is further continued for reaction 10 hours after being added dropwise.End of reaction Reaction mixture is cooled to room temperature afterwards, pours the mixture into 300mL ice water and stirs 0.5 hour, there is solid precipitation, is filtered, (60mL x 3) is washed with water in filter cake, obtains yellow solid 14g, yield: 95%.
LC-MS:(M+1) m/z=296.0.
Step 2: the synthesis of 4- (4- bromobenzene oxygroup) aniline
By 1- bromo- 4- (4-nitrophenoxy) phenyl (14.0g, 47.7mmol), iron powder (11.2g, 200mmol), ethyl alcohol (180mL), water (60mL) and 35% hydrochloric acid (0.3g) are added in reaction flask, replace nitrogen, are warming up to 90 DEG C and are stirred 12 hours. After completion of the reaction, it filters, filtrate is concentrated under reduced pressure, ethyl acetate dilution (150mL) is added, is washed with brine (50mL x 3), point Liquid, organic phase are dried, filtered with anhydrous magnesium sulfate, are concentrated under reduced pressure, and residue separates [PE/EA (v/v)=2/ through silica gel column chromatography 1], brick-red solid 7.8g is obtained, yield: 64%.
LC-MS:(M+1) m/z=264.0.
Step 3: the synthesis of 4- (4- bromobenzene oxygroup) phenol
Under nitrogen protection, 4- (4- bromobenzene oxygroup) aniline (5.26g, 20mmol) is dissolved in the glacial acetic acid of 20mL, then 55 DEG C are to slowly warm up to, after solution clarification, hydrochloric acid solution (2N, 20mL) slowly is added dropwise, is added dropwise, add under condition of ice bath Enter sodium nitrite solution (2N, 20mL), after reaction mixture clarification, 38% fluoborate solution (25mL) is added, then exists It is reacted 12 hours under conditions of 80 DEG C.After reaction, system is cooled to room temperature, and stands 10 hours, there is a large amount of precipitating It generates, mixture is filtered, obtaining yellow solid is NITRODIAZONIUM FLUOROBORATE.
In the acetic anhydride that NITRODIAZONIUM FLUOROBORATE is dissolved in 50mL under conditions of nitrogen protection, it is then slowly ramped to 110 DEG C reaction 4 hours, acetic anhydride is removed under reduced pressure, obtains the grease of black.The sodium hydroxide solution of 50mL ethyl alcohol and 45% is added (30mL), heating reflux reaction 10 hours.The hydrochloric acid that 2N is added adjusts pH=6, and ethyl acetate extracts (80mL x 3), saturation food Salt water is washcoated (30mL x 3), and anhydrous sodium sulfate dries, filters, and filtrate is concentrated under reduced pressure, and residue is purified by silica gel column chromatography [PE/EA (v/v)=3/1], obtains yellow solid 2.9g, yield: 55.8%.
LC-MS:(M+1) m/z=265.2.
Using corresponding raw material, prepared by the similar synthetic method of intermediate 4- (4- bromobenzene oxygroup) phenol, i.e., The midbody compound in table 1 can be obtained.
Table 1
Intermediate: the synthesis of 2- methyl -3- oxopentanoic acid methyl ester
Under nitrogen protection, sodium hydride (9.5g, 0.6eqv.60%wt) and tetrahydrofuran (100mL) addition 500mL is mono- It in mouth flask, stirs after twenty minutes, is added dropwise ethyl propionate (40g, 392mmol) at -10 DEG C, continue at room temperature after dripping off anti- It answers 5 hours.It is filtered to remove solid, tetrahydrofuran is distilled off in filtrate decompression, and (50mL x 3) is extracted with ethyl acetate in crude product, Merge organic phase, is concentrated under reduced pressure to give yellow liquid 26.0g, yield: 43.6%.
LC-MS:(M+1) m/z=159.1.
Intermediate: N- (4- (benzo [d] [1,3] dioxolane -5- base oxygroup) -3,5- dichlorophenyl) -2- acetyl bromide The synthesis of amine
Step 1: the synthesis of 5- (the chloro- 4-nitrophenoxy of 2,6- bis-) benzo [d] [1,3] dioxolane
By benzo [d] [1,3] dioxolane -5- alcohol (10g, 72mmol), the chloro- 4- fluoronitrobenzene of 3,5- bis- (22.7g, 108mmol), potassium carbonate (15mg, 108mmol) and the n,N-Dimethylformamide of 80mL drying are added in 250mL single-necked flask, It is reacted 15 hours in 80 DEG C under nitrogen protection.It is cooled to room temperature, ice water is added and is vigorously stirred, has solid precipitation, filters and use water It washs filter cake (30mL x 3), it is dry, light yellow solid 18g is obtained, yield: 71.7%.
LC-MS:(M+1) m/z=328.0.
Step 2: the synthesis of 4- (benzo [d] [1,3] dioxolane -5- base oxygroup) -3,5- dichloroaniline
By 5- (the chloro- 4-nitrophenoxy of 2,6- bis-) benzo [d] [1,3] dioxolane (10g, 30.6mmol) ammonium chloride 500mL single port bottle is added in the mixed solution [ethanol/water (v/v)=10/1,220mL] of (2.5g, 45.9mmol) and ethyl alcohol and water In, it is slowly added to reduced iron powder (3.4g, 62mmol) after being warming up to reflux, is continued back flow reaction 5 hours after adding.It is down to room temperature After be filtered to remove iron powder, ethyl alcohol is distilled off in filtrate decompression, and obtained dope adds water and with salt acid for adjusting pH, and solid is precipitated and produces Object, filtering, obtains light yellow solid 7g, yield: 77.8%.
LC-MS:(M+1) m/z=298.0.
Step 3: N- (4- (benzo [d] [1,3] dioxolane -5- base oxygroup) -3,5- dichlorophenyl) -2- acetyl bromide The synthesis of amine
4- (benzo [d] [1,3] dioxolane -5- base oxygroup) -3,5- dichloroaniline (1000mg, 3.36mmol) is molten Solution (20mL) in methylene chloride, under nitrogen protection, be added the stirring of 1mL triethylamine be added dropwise after ten minutes bromoacetyl bromide (1340mg, 6.7mmol), it is concentrated under reduced pressure after being stirred at room temperature 10 hours and removes methylene chloride, crude product ethyl acetate (50mL x 3) takes off Faint yellow solid 1300mg is obtained after molten, yield: 92.8%.
LC-MS:(M+1) m/z=419.9.
Intermediate: the synthesis of the bromo- N- of 2- (4- ((1- bromonaphthalene base -2- base) oxygroup) -3,5- dichlorophenyl) acetamide
Step 1: the synthesis of the bromo- 2- of 1- (the chloro- 4-nitrophenoxy of 2,6- bis-) naphthalene
By 1- bromonaphthol (5g, 22.5mmol), the chloro- 4- fluoronitrobenzene (7.6g, 34mmol) of 3,5- bis-, potassium carbonate (6.2g, It 45mmol) is added in 250mL single-necked flask with the n,N-Dimethylformamide of 80mL drying, is reacted under nitrogen protection in 90 DEG C 15 hours.Reaction terminates to be cooled to room temperature, and ice water is added and is vigorously stirred, has solid precipitation, filters and filter cake (30mL x is washed with water 3), dry, light yellow solid 7g is obtained, yield: 76.1%.
LC-MS:(M+1) m/z=411.9.
Step 2: the synthesis of 4- ((1- bromonaphthalene base -2- base) oxygroup) -3,5- dichloroaniline
By the bromo- 2- of 1- (the chloro- 4-nitrophenoxy of 2,6- bis-) naphthalene (5g, 12.2mmol) ammonium chloride (1.3g, 24.5mmol) It is added in 250mL single port bottle with the mixed solution [ethanol/water (v/v)=10/1,150mL] of ethyl alcohol and water, after being warming up to reflux It is slowly added to reduced iron powder (2.5g, 45mmol), is continued back flow reaction 5 hours after adding.It is cooled to room temperature and is filtered to remove iron powder, Ethyl alcohol is distilled off in filtrate decompression, and obtained dope adds water and with salt acid for adjusting pH, and solid product is precipitated, and filtering obtains shallow Yellow solid 3.5g, yield: 76.1%.
LC-MS:(M+1) m/z=381.9.
Step 3: the synthesis of the bromo- N- of 2- (4- ((1- bromonaphthalene base -2- base) oxygroup) -3,5- dichlorophenyl) acetamide
4- ((1- bromonaphthalene base -2- base) oxygroup) -3,5- dichloroaniline (1000mg, 2.6mmol) is dissolved in methylene chloride In (20mL), under nitrogen protection, the stirring of 1mL triethylamine is added, bromoacetyl bromide (1050mg, 5.2mmol) is added dropwise after ten minutes, In It stirs 10 hours at room temperature.It is concentrated under reduced pressure and removes methylene chloride, crude product ethyl acetate extracts (50mL x 3), and precipitation obtains Faint yellow solid 920mg, yield: 70.7%.
LC-MS:(M+1) m/z=501.8.
Intermediate: the synthesis of 1- (6- chloropyridine -2- base) -3- methyl-1 H- pyrazoles -4- formyl chloride
Step 1: the synthesis of (E)-ethyl 2- (methoxymethylene) -3- ketobutyric acid
By ethyl acetoacetate (100g, 0.769mol), triethyl orthoformate (171g, 1.15mol) and acetic anhydride (118g, 1.15mol) is added in 500mL single-necked flask, is warming up to 120 DEG C and carries out liquid separation, continues after no coupling product steams It is warming up to 140 DEG C to continue to be fractionated by-product, vacuum distillation removes low boiling impurity after reaction 5 hours, distills under normal pressure, obtains orange Yellow liquid 92.7g, yield: 65%.
LC-MS:(M+1) m/z=187.1.
Step 2: the synthesis of 1- (6- chloropyridine -2- base) -3- methyl-1 H- pyrazoles -4- Ethyl formate
Chloro- 6 hydrazino pyridine (1.5g, 10mmol) of 2-, ethyl alcohol (100mL) are added in 250mL single-necked flask, at -10 DEG C Then the ethanol solution of (E)-ethyl 2- (methoxymethylene) -3- ketobutyric acid is slowly dropped by lower cooling 15 minutes, stirring Continue to be stirred at room temperature 10 hours after 4 hours, is evaporated under reduced pressure, obtains faint yellow solid 2.8g, yield: 90%.
LC-MS:(M+1) m/z=265.9.
Step 3: the synthesis of 1- (6- chloropyridine -2- base) -3- methyl-1 H- pyrazoles -4- formic acid
By 1- (6- chloropyridine -2- base) -3- methyl-1 H- pyrazoles -4- Ethyl formate (2.77g, 0.01mmol), 50mL second Alcohol is added in 250mL single-necked flask, is warming up at 85 DEG C and flows back, and sodium hydroxide (0.827g, 0.015mol) then is added, reflux 5 hour, hydrochloric acid adjusting pH=5 is added after being cooled to room temperature, solid is precipitated, filtering obtains white solid product 1.8g, yield: 72.3%.
LC-MS:(M+1) m/z=238.0.
Step 4: the synthesis of 1- (6- chloropyridine -2- base) -3- methyl-1 H- pyrazoles -4- formyl chloride
By 1- (6- chloropyridine -2- base) -3- methyl-1 H- pyrazoles -4- formic acid (1g, 4.2mmol), thionyl chloride (10mL) It is added in 100mL single-necked flask, is reacted 5 hours under room temperature environment under nitrogen protection.Then it is sub- to remove dichloro for vacuum distillation Sulfone obtains yellow liquid product 1g, yield 95%.
LC-MS:(M+1) m/z=256.0.
The conjunction of embodiment 1:6- (4- (4- bromobenzene oxygroup) phenoxy group) -2- ethyl -3,7- dimethyl quinoline -4- yl acetate At
Step 1: the synthesis of 1- (4- (4- bromobenzene oxygroup) phenoxy group) -2- methyl -4- nitrobenzene
By 4- (4- bromobenzene oxygroup) phenol (2.9g, 11mmol), potassium carbonate (2.3g, 16.7mmol), N, N- dimethyl methyl Amide (25mL) is added in 100mL single port bottle, and reaction is warming up at 60 DEG C and is stirred 2 hours.Then it is fluoro- that 4- is slowly added dropwise The n,N-Dimethylformamide solution (10mL) of 3- methyl nitrobenzene (1.72g, 11mmol), it is 10 small that the reaction was continued after being added dropwise When.Reaction mixture is cooled to room temperature after completion of the reaction, pour the mixture into 100mL ice water and is stirred 0.5 hour, is had Solid is precipitated, and filtering, filter cake is washed with water (30mL x 3) three times, obtains yellow solid 3.35g, yield: 76.3%.
LC-MS:(M+1) m/z=400.1.
Step 2: the synthesis of 4- (4- (4- bromobenzene oxygroup) phenoxy group) -3- methylaniline
By 1- (4- (4- bromobenzene oxygroup) phenoxy group) -2- methyl -4- nitrobenzene (3.3g, 8.3mmol), iron powder (3.1g, 55mmol), ethyl alcohol (50mL), water (20mL) and 35% hydrochloric acid (0.1mL) are added in reaction flask, are replaced nitrogen, are warming up to 90 DEG C stirring 12 hours.After completion of the reaction, solid impurity is filtered out, after filtrate decompression is concentrated, ethyl acetate dilution is added (60mL) is washed with brine (15mL x 3), and liquid separation, organic phase anhydrous magnesium sulfate dries, filters, and filtrate is concentrated under reduced pressure, remaining Object separates [PE/EA (v/v)=2/1] through silica gel column chromatography, obtains yellow oil 1.8g, yield: 60.5%.
LC-MS:(M+1) m/z=370.1.
Step 3: the synthesis of -4 (1H) -one of 6- (4- (4- bromobenzene oxygroup) phenoxy group) -2- ethyl -3,7- dimethyl quinoline
By 4- (4- (4- bromobenzene oxygroup) phenoxy group) -3- methylaniline (1.8g, 5mmol), 2- methyl -3- oxopentanoic acid second Ester (0.93g, 5.9mmol), glacial acetic acid (0.1g, 1.67mmol), toluene (50mL), which is added to have under nitrogen protection, divides water In the 100mL single port bottle of device, reaction temperature is then risen to 120 DEG C, and after reflux water-dividing 18 hours that toluene is molten at 120 DEG C Agent steams, and obtains grease；Grease is dissolved with hexichol ethereal solution (10mL), and reaction temperature is risen to 255 DEG C, stirring is anti- After answering 30 minutes, the reaction is cooled to room temperatures, are slowly added into petroleum ether (30mL), there is solid precipitation, filter out solid, and use stone Oily ether/ethyl acetate mixture washing (v/v=20/1,10mL x 3), obtains beige solid 1.2g, yield: 52%.
LC-MS:(M+1) m/z=464.1.
Step 4: the conjunction of 6- (4- (4- bromobenzene oxygroup) phenoxy group) -2- ethyl -3,7- dimethyl quinoline -4- yl acetate At
By -4 (1H) -one of 6- (4- (4- bromobenzene oxygroup) phenoxy group) -2- ethyl -3,7- dimethyl quinoline (0.4g, It 0.86mmol) is dissolved in the acetic anhydride of 10mL, under nitrogen protection, is warming up to 130 DEG C and reacts 12 hours.Solvent is steamed, second is added Acetoacetic ester (20mL), salt water washing (10mL x 3), organic phase is dried, filtered with magnesium sulfate, and filtrate, silica gel column chromatography point is concentrated From [PE/EA (v/v)=10/1], yellow solid 0.27g is obtained, yield: 61%.
1H NMR(400MHz,CDCl3)δ(ppm):7.92-7.84(m,1H),7.38-7.28(m,4H),7.12-6.81 (m, 5H), 3.2-3.1 (m, 2H), 2.71 (s, 3H), 2.48 (s, 3H), 2.31 (s, 3H), 1.41 (td, J=8.1,2.1Hz, 3H).
LC-MS:(M+1) m/z=507.1.
Midbody compound in table 1 is prepared with corresponding material by the similar synthetic method of embodiment 1, i.e., The target compound in table 2 can be obtained.
Table 2
The synthesis of embodiment 20:2- ethyl -3,7- dimethyl -6- (4- phenoxy-phenoxy) quinolyl-4 acetic acid esters
Step 1: the synthesis of 2- methyl -4- nitro -1- (4- phenoxy-phenoxy) benzene
By 4- phenoxy phenyl (2.03g, 11mmol), potassium carbonate (2.3g, 16.7mmol), N,N-dimethylformamide (25mL) is added in 100mL single port bottle, and reaction is warming up at 60 DEG C and is stirred 2 hours.Then the fluoro- 3- first of 4- is slowly added dropwise It is small to be further continued for reaction 10 for the n,N-Dimethylformamide solution (10mL) of base nitrobenzene (1.72g, 11mmol) after being added dropwise When.It is cooled to room temperature, then pour the mixture into 100mL ice water and is stirred 0.5 hour, there is solid precipitation, is filtered out solid Body is washed with water (30mL x 3) three times, obtains yellow solid 3.0g, yield: 85%.
Step 2: the synthesis of 3- methyl -4- (4- phenoxy-phenoxy) aniline
By 2- methyl -4- nitro -1- (4- phenoxy-phenoxy) benzene (2.56g, 8.0mmol), iron powder (3.1g, 55mmol), ethyl alcohol (50mL), water (20mL) and 35% hydrochloric acid (0.1mL) are added in reaction flask, are replaced nitrogen, are warming up to 90 It DEG C is stirred to react 12 hours.After completion of the reaction, solid impurity is filtered out, after filtrate is concentrated, ethyl acetate dilution is added (60mL) is washed with brine (15mL x 3), and organic phase anhydrous magnesium sulfate is dry, and concentration, silica gel column chromatography separates [PE/EA (v/ V)=2/1], yellow oil 2.1g is obtained, yield: 90%.
Step 3: the synthesis of 2- ethyl -3,7- dimethyl -6- (4- phenoxy-phenoxy) quinoline -4 (1H) -one
By 3- methyl -4- (4- phenoxy-phenoxy) aniline (1.45g, 5mmol), 2- methyl -3- oxopentanoic acid methyl ester (0.93g, 5.9mmol), glacial acetic acid (0.1g, 1.67mmol), toluene (50mL) are added under nitrogen protection with water segregator 100mL single port bottle in, reaction temperature is then risen into 120 DEG C, and reflux water-dividing 18 hours at 120 DEG C.By toluene solvant It steams, obtains grease, hexichol ethereal solution (10ml) is then added and dissolves grease, and reaction temperature is risen to 255 DEG C, stirs After mixing reaction 30 minutes, the reaction is cooled to room temperatures, are slowly added into 30mL petroleum ether, have solid precipitation, filter out solid, are used in combination Petrol ether/ethyl acetate mixed solution washs (v/v=20/1,10mL x 3), obtains beige solid 1.3g, yield: 67.7%.
Step 4: the synthesis of 2- ethyl -3,7- dimethyl -6- (4- phenoxy-phenoxy) quinolyl-4 acetic acid esters
2- ethyl -3,7- dimethyl -6- (4- phenoxy-phenoxy) quinoline -4 (1H) -one (0.31g, 0.8mmol) is molten In the acetic anhydride of 10mL, under nitrogen protection, it is warming up to 130 DEG C and reacts 12 hours.Solvent is steamed, ethyl acetate is added (20mL) is then washed with brine (10mL x 3), and organic phase is dry with magnesium sulfate, and concentration, silica gel column chromatography separates [PE/AE (v/v)=10/1 yellow solid 0.22g], is obtained, yield: 62.5%.
1H NMR(400MHz,CDCl3)δ(ppm):7.97-7.87(m,2H),7.41-7.26(m,2H),7.17-6.93 (m, 6H), 6.89 (d, J=8.6Hz, 1H), 3.14-2.93 (m, 2H), 2.70-2.36 (m, 6H), 2.27 (s, 3H), 1.39 (ddd, J=16.3,10.5,5.0Hz, 3H)；
LC-MS:(M+1) m/z=428.2.
By intermediate 2- ethyl -3,7- dimethyl -6- (4- phenoxy-phenoxy) quinoline -4 (1H) -one and different materials Reaction, can be obtained the target compound in table 3.
Table 3
The synthesis of embodiment 29:2- (difluoromethyl) -7- methyl -6- (4- phenoxy-phenoxy) quinolyl-4 acetic acid esters
Step 1: the synthesis of 2- (difluoromethyl) -7- methyl -6- (4- phenoxy-phenoxy) quinoline -4 (1H) -one
By 3- methyl -4- (4- phenoxy-phenoxy) aniline (1.45g, 5mmol), difluoro ethyl acetoacetate (0.98g, 5.9mmol), glacial acetic acid (0.1g, 1.67mmol), toluene (50mL) are added to the 100mL with water segregator under nitrogen protection In single port bottle, reaction temperature is then risen into 120 DEG C, and reflux water-dividing 18 hours at 120 DEG C.Toluene solvant is steamed, is obtained To grease, hexichol ethereal solution (10mL) is added and dissolves grease, and reaction temperature is risen to 255 DEG C, is stirred to react 30 points Zhong Hou, the reaction is cooled to room temperatures, are slowly added into 30mL petroleum ether, there is solid precipitation, filter out solid, and with petroleum ether/second Acetoacetic ester mixed solution washs (v/v=20/1,10mL x 3), obtains beige solid 1.6g, yield: 80%.
Step 2: the synthesis of 2- (difluoromethyl) -7- methyl -6- (4- phenoxy-phenoxy) quinolyl-4 acetic acid esters
By 2- (difluoromethyl) -7- methyl -6- (4- phenoxy-phenoxy) quinoline -4 (1H) -one (0.34g, 0.8mmol) It is dissolved in the acetic anhydride of 10mL, under nitrogen protection, is warming up to 130 DEG C and reacts 12 hours.Stop reaction, steam solvent, second is added Acetoacetic ester (20mL) is then washed with brine (10mL x 3), and organic phase is dry with magnesium sulfate, is concentrated under reduced pressure, residue silica gel Column chromatography for separation [PE/EA (v/v)=10/1], obtains yellow solid 0.22g, yield: 62.5%.
1H NMR(400MHz,CDCl3) δ (ppm): 8.04 (d, J=4.3Hz, 1H), 7.55 (s, 1H), 7.48 (s, 1H), 7.40-7.33(m,2H),7.17-7.00(m,5H),6.96-6.93(m,2H),6.8-6.6(m,1H),2.51(s,3H),2.38 (s,3H)；
LC-MS:(M+1) m/z=436.4.
Embodiment 30:2- (difluoromethyl) -7- methyl -6- (4- phenoxy-phenoxy) quinolyl-4 1- (6- chloropyridine - 2- yl) -3- methyl-1 H- pyrazoles -4- formic acid esters synthesis
2- (difluoromethyl) -7- methyl -6- (4- phenoxy-phenoxy) quinoline -4 (1H) -one (1g, 2.5mmol) is dissolved In methylene chloride (20mL), under nitrogen protection, the stirring of 1mL triethylamine is added, 1- (6- chloropyridine -2- base)-is added after ten minutes 3- methyl-1 H- pyrazoles -4- formyl chloride (0.99g, 3.75mmol) is stirred at room temperature 10 hours.It is concentrated under reduced pressure and removes dichloromethane Alkane, residue separate [petrol ether/ethyl acetate (v/v)=4/1] through silica gel column chromatography, obtain yellow solid 210mg, yield: 12.7%.
LC-MS:(M+1) m/z=612.2.
The synthesis of embodiment 31:5,7- bis- chloro-2-methyl -6- (4- phenoxy-phenoxy) quinolyl-4 methyl carbonic
Step 1: the synthesis of the chloro- 4- of 3,5- bis- (4- phenoxy phenoxy base) nitrobenzene
P-phenoxyphenol (10g, 53mmol), potassium carbonate (11.1g, 80mmol) are added in 100mL single port bottle, are added 35mL dry n,N-Dimethylformamide, after being stirred at room temperature 30 minutes, is slowly added to the fluoro- 5- nitrobenzene of the chloro- 2- of 1,3- bis- (14.6g, 69mmol) is added and is reacted 12 hours in lower 100 DEG C of nitrogen protection.It is cooled to room temperature, ice water is added and is vigorously stirred, has Solid is precipitated, and filters, and filter cake is washed with water (10mL x 3), dry, obtains light yellow solid 16g, yield: 80%.
LC-MS:(M+1) m/z=376.0.
Step 2: the synthesis of the chloro- 4- of 3,5- bis- (4- phenoxy phenoxy base) aniline
By the chloro- 4- of 3,5- bis- (4- phenoxy phenoxy base) nitrobenzene (10g, 26.6mmol) ammonium chloride (2.2g, 40mmol) and The mixed solution (v/v=10/1,220mL) of ethyl alcohol and water is added in 500mL single port bottle, is slowly added to restore after being warming up to reflux Iron powder (3g, 54mmol) continues back flow reaction 5 hours after adding.It is cooled to room temperature and is filtered to remove iron powder, filtrate decompression distillation removes Ethyl alcohol is removed, obtained dope adds water and with salt acid for adjusting pH, and solid product is precipitated, light yellow solid 7g is obtained after filtering, receives Rate: 77%.
LC-MS:(M+1) m/z=346.0.
Step 3: the synthesis of bis- chloro-2-methyl -6- of 5,7- (4- phenoxy phenoxy base) quinoline -4 (1H) -one
Under nitrogen protection, by the chloro- 4- of 3,5- bis- (4- phenoxy phenoxy base) aniline (6g, 17.4mmol), ethyl acetoacetate (11.3g, 85mmol), glacial acetic acid (2ml) and toluene (60mL) are added in the 100mL single port bottle with water segregator, are heated to 130 DEG C, reflux water-dividing 12 hours.It is concentrated under reduced pressure and removes toluene, obtain brown oil.It is added diphenyl ether (15mL), is heated to It 250 DEG C, stirs 30 minutes, the reaction is cooled to room temperatures, are slowly added into petroleum ether (30mL), there is solid precipitation, filter, and filter cake is used Petrol ether/ethyl acetate solution washs (v/v=10/1,10mL x 3), obtains sepia solid 3.9g, yield: 54.2%.
LC-MS:(M+1) m/z=412.04.
Step 4: the synthesis of bis- chloro-2-methyl -6- of 5,7- (4- phenoxy phenoxy base) quinolyl-4 methyl carbonic
Bis- chloro-2-methyl -6- of 5,7- (4- phenoxy phenoxy base) quinoline -4 (1H) -one (800mg, 1.9mmol) is dissolved in In methylene chloride (20mL), under nitrogen protection, be added 1mL triethylamine stirring after ten minutes be added methylchloroformate (530mg, 10mmol), it is stirred at room temperature 10 hours.It is concentrated under reduced pressure and removes methylene chloride, residue separates [PE/EA through silica gel column chromatography (v/v)=5/1 white solid 325mg], is obtained, yield: 35.5%.
1H NMR(400MHz,CDCl3)δ(ppm):7.87(m,1H),7.41-7.26(m,3H),7.17-6.91(m,6H), 6.90(d,1H),3.80(s,3H),2.70-2.46(s,3H)；
LC-MS:(M+1) m/z=470.1.
By corresponding material and 5, bis- chloro-2-methyl -6- of 7- (4- phenoxy phenoxy base) quinoline -4 (1H) -one is reacted, The target compound in table 4 can be prepared.
Table 4
Embodiment 36:2- ethyl -6- ((fluoro- [1,1'- the biphenyl] -4- base of 4'-) oxygroup) -3,7- dimethyl quinoline -4- base The synthesis of acetic acid esters
Step 1: the synthesis of the fluoro- 4'- of 4- (2- methyl -4- nitrobenzophenone) -1,1'- biphenyl
100mL single port is added in the fluoro- 4'- xenol (1.02g, 5.40mmol) of 4-, potassium carbonate (1.35g, 9.8mmol) In bottle, the dry n,N-Dimethylformamide of 10mL is added, after being stirred at room temperature 30 minutes, is slowly added to 3- methyl -4- fluorine nitro Benzene (760mg, 4.9mmol) is added and is reacted 12 hours in lower 100 DEG C of nitrogen protection.It is cooled to room temperature, ice water is added and is vigorously stirred, There is solid precipitation, filter and is washed with water filter cake (15mL x 3), it is dry, light yellow solid 1.52g is obtained, yield: 87.1%.
LC-MS:(M+1) m/z=324.1.
Step 2: the synthesis of 4- ((fluoro- [1,1'- the xenyl] -4- base of 4'-) oxygroup) -3- methylaniline
By the fluoro- 4'- of 4- (2- methyl -4- nitrobenzophenone) -1,1'- biphenyl (1.36g, 4.22mmol), ammonium chloride (271mg, It 5.06mmol) is added in 100mL single port bottle with the mixed solution (v/v=10/1,33mL) of ethyl alcohol and water, delays after being warming up to reflux It is slow that reduced iron powder (945mg, 16.9mmol) is added, continue back flow reaction 5 hours after adding.Ethyl alcohol is removed under reduced pressure, water is added (10mL), and extracted with ethyl acetate (20mL x 3), merge organic phase, saturated common salt water washing (20mL x 3), anhydrous sulphur Sour magnesium dries, filters, and filtrate is removed under reduced pressure, and obtains light yellow solid 1.09g, yield: 88.2%.
LC-MS:(M+1) m/z=294.2.
Step 3: 2- ethyl -6- ((fluoro- [1,1'- the biphenyl] -4- base of 4'-) oxygroup) -3,7- dimethyl quinoline -4- (1H) - The synthesis of ketone
Under nitrogen protection, by 4- ((fluoro- [1,1'- the xenyl] -4- base of 4'-) oxygroup) -3- methylaniline (1.08g, 3.7mmol), 2- methyl -3- oxopentanoic acid methyl ester (760mg, 4.81mmol), glacial acetic acid (0.2g) and toluene (20mL) are added to In 100mL single port bottle with water segregator, it is heated to 120 DEG C, reflux water-dividing 18 hours.It is concentrated under reduced pressure and removes toluene, obtain palm fibre Color grease.It is added diphenyl ether (10mL), is heated to 255 DEG C, stir 30 minutes, the reaction is cooled to room temperatures, are slowly added into stone Oily ether (20mL), there is solid precipitation, and filtering, filter cake washs (v/v=10/1,10mL x 3) with petrol ether/ethyl acetate solution, Obtain sepia solid 695mg, yield: 48.6%.
LC-MS:(M+1) m/z=388.1.
Step 4: 2- ethyl -6- ((fluoro- [1,1'- the biphenyl] -4- base of 4'-) oxygroup) -3,7- dimethyl quinoline -4- base second The synthesis of acid esters
By 2- ethyl -6- ((fluoro- [1,1'- the biphenyl] -4- base of 4'-) oxygroup) -3,7- dimethyl quinoline -4- (1H) -one (356mg, 0.92mmol) is dissolved in acetic anhydride (10mL), under nitrogen protection, is heated to 120 DEG C and is reacted 12 hours.It depressurizes dense Contracting removes acetic anhydride, is added ethyl acetate (20mL), saturated common salt water washing (10mL x 3), and organic phase is dry with anhydrous magnesium sulfate Dry, filtrate is concentrated under reduced pressure in filtering, and residue separates [petrol ether/ethyl acetate (v/v)=10/1] through silica gel column chromatography, obtains Light yellow solid 202mg, yield: 51.2%.
1H NMR(400MHz,CDCl3)δ(ppm):7.99(s,1H),7.55-7.52(m,4H),7.16-7.12(m,3H), 7.03 (d, J=8.8Hz, 2H), 3.03 (q, J=7.6Hz, 2H), 2.44 (s, 3H), 2.37 (s, 3H), 2.28 (s, 3H), 1.40 (t, J=7.6Hz, 3H)；
LC-MS:(M+1) m/z=430.10.
Embodiment 37:2- (difluoromethyl) -8- methyl -6- (2- methyl -4- (4- toluyl amido) phenoxy group) quinoline The synthesis of quinoline -4- base 4- methyl benzoic acid ester
Step 1: the synthesis of 2- methyl -4- (2- methyl -4-nitrophenoxy) aniline
4- amino -3- methylphenol (0.62g, 5.00mmol), potassium carbonate (1.35g, 9.8mmol) addition 100mL is mono- In mouth bottle, the dry n,N-Dimethylformamide of 10mL is added, after being stirred at room temperature 30 minutes, is slowly added to 3- methyl -4- fluorine nitre Base benzene (760mg, 4.9mmol) is added and is reacted 12 hours in lower 100 DEG C of nitrogen protection.It is cooled to room temperature, ice water is added and acutely stirs It mixes, there is solid precipitation, filter and be washed with water filter cake (15mL x 3), be dried to obtain light yellow solid 1.52g, yield: 88.1%.
LC-MS:(M+1) m/z=259.1.
Step 2: the synthesis of 2- (difluoromethyl) -8- methyl -6- (2- methyl -4-nitrophenoxy) quinoline -4 (1H) -one
Under nitrogen protection, by 2- methyl -4- (2- methyl -4-nitrophenoxy) aniline (1.04g, 4.0mmol), difluoro second It is mono- that ethyl acetoacetic acid ethyl ester (830mg, 5.00mmol), glacial acetic acid (0.2g) and toluene (20mL) are added to the 100mL with water segregator In mouth bottle, it is heated to 120 DEG C, reflux water-dividing 18 hours.It is concentrated under reduced pressure and removes toluene, obtain brown oil.Diphenyl ether is added (10mL) is heated to 255 DEG C, stirs 30 minutes, the reaction is cooled to room temperatures, are slowly added into petroleum ether (20mL), there is solid analysis Out, it filters, filter cake washs (v/v=10/1,10mL x 3) with petrol ether/ethyl acetate solution, obtains sepia solid 786mg, yield: 54.5%.
LC-MS:(M+1) m/z=361.2.
Step 3: the synthesis of -4 (1H) -one of 6- (4- amino-2-methyl phenoxy group) -2- difluoromethyl -8- methylquinoline
By 2- (difluoromethyl) -8- methyl -6- (2- methyl -4-nitrophenoxy) quinoline -4 (1H) -one (0.722g, 2.00mmol), the mixed solution [ethanol/water (v/v)=10/1,15mL] of ammonium chloride (134mg, 2.50mmol) and ethyl alcohol and water It is added in 50mL single port bottle, is slowly added to reduced iron powder (336mg, 6.0mmol) after being warming up to reflux, it is anti-to continue reflux after adding It answers 5 hours and is converted completely to raw material.Ethyl alcohol is removed under reduced pressure, is added water (10mL), and is extracted with ethyl acetate (20mL x 3), has Machine mutually merges to be washed with saturated salt solution (20mL x 3), and organic phase is dried, filtered with anhydrous magnesium sulfate, and filtrate is removed under reduced pressure, Light yellow solid 0.593g is obtained, yield: 89.5%.
LC-MS:(M+1) m/z=331.2.
Step 4: 2- difluoromethyl -8- methyl -6- (2- methyl -4- (4- methylbenzyl acyl group) phenoxy group) quinoline -4- The synthesis of base 4- methyl benzoic acid ester
By -4 (1H) -one of 6- (4- amino-2-methyl phenoxy group) -2- difluoromethyl -8- methylquinoline (331mg, It 1.00mmol) is dissolved in methylene chloride (2.0mL) with triethylamine (303mg, 3.00mmol), under nitrogen protection, is added to first Base chlorobenzoyl chloride (464mg, 3.00mmol) reacts 12 hours.It is concentrated under reduced pressure and removes solvent, be added ethyl acetate (20mL), saturation Brine It (10mL x 3), organic phase is dried, filtered with anhydrous magnesium sulfate, filtrate is concentrated under reduced pressure, residue is through silicagel column Chromatography [petrol ether/ethyl acetate (v/v)=10/1], obtains light yellow solid 278mg, yield: 49.1%.
1H NMR(400MHz,CDCl3) δ (ppm): 8.05 (d, J=8.0Hz, 2H), 7.82-7.76 (m, 3H), 7.64 (d, J=2.4Hz, 1H), 7.50-7.47 (m, 1H), 7.36-7.30 (m, 4H), 7.18 (d, J=2.4Hz, 1H), 7.02 (d, J= 8.0Hz, 1H), 6.81 (t, J=55.2Hz, 1H), 2.82 (s, 3H), 2.47 (s, 3H), 2.38 (s, 3H), 2.24 (s, 3H)；
LC-MS:(M+1) m/z=567.15.
Embodiment 38:4- ((4- ((2- chloronicotinoyl base) oxygroup) -2- (difluoromethyl) -8- methylquinoline -6- base) oxygroup) The synthesis of phenyl 2- chlorine apellagrin ester
Step 1: the synthesis of 4- (3- methyl -4-nitrophenoxy) phenol
Biphenol (0.550g, 5.00mmol), potassium carbonate (1.35g, 9.8mmol) will be added in 100mL single port bottle, be added Enter the dry n,N-Dimethylformamide of 10mL, after being stirred at room temperature 30 minutes, is slowly added to 2- methyl -4- fluoronitrobenzene (760mg, 4.9mmol) is added and is reacted 12 hours in lower 100 DEG C of nitrogen protection.It is cooled to room temperature, ice water is added and is vigorously stirred, has Solid is precipitated, and filters and is washed with water filter cake (15mL x 3), dry, obtains light yellow solid 1.07g, yield: 89.3%.
LC-MS:(M+1) m/z=246.1.
Step 2: the synthesis of 4- (4- amino -3- methylphenoxy) phenol
By 4- (3- methyl -4-nitrophenoxy) phenol (1.04g, 4.22mmol), ammonium chloride (271mg, 5.06mmol) It is added in 100mL single port bottle with the mixed solution [ethanol/water (v/v)=10/1,33mL] of ethyl alcohol and water, delays after being warming up to reflux It is slow that reduced iron powder (945mg, 16.9mmol) is added, continue back flow reaction 5 hours after adding.Ethyl alcohol is removed under reduced pressure, water is added (10mL), and (20mL x 3) is extracted with ethyl acetate, merge organic phase, saturated common salt water washing (20mL x 3), anhydrous sulphur Sour magnesium dries, filters, and filtrate is removed under reduced pressure, and obtains light yellow solid 0.801g, yield: 87.9%.
LC-MS:(M+1) m/z=216.1.
Step 3: the synthesis of 2- difluoromethyl -6- (4- hydroxyphenoxy) -8- methylquinoline -4 (1H) -one
Under nitrogen protection, by 4- (4- amino -3- methylphenoxy) phenol (0.799g, 3.7mmol), difluoro acetoacetate Ethyl ester (830mg, 5.00mmol), glacial acetic acid (0.2g) and toluene (20mL) are added in the 100mL single port bottle with water segregator, 120 DEG C are heated to, reflux water-dividing 18 hours, is concentrated under reduced pressure and removes toluene, obtain brown oil.It is added diphenyl ether (10mL), 255 DEG C are heated to, is stirred 30 minutes, the reaction is cooled to room temperatures, are slowly added into petroleum ether (20mL), there is solid precipitation, it filters, Filter cake washs (v/v=10/1,10mL x 3) with petrol ether/ethyl acetate solution, obtains sepia solid 550mg, yield: 46.9%.
LC-MS:(M+1) m/z=318.2.
Step 4: 4- ((4- ((2- chloronicotinoyl base) oxygroup) -2- (difluoromethyl) -8- methylquinoline -6- base) oxygroup) benzene The synthesis of base 2- chlorine apellagrin ester
By 2- difluoromethyl -6- (4- hydroxyphenoxy) -8- methylquinoline -4 (1H) -one (318mg, 1.00mmol) and three Ethamine (303mg, 3.00mmol) is dissolved in methylene chloride (2.0mL), under nitrogen protection, addition 2- chloronicotinoyl chloride (424mg, 3.00mmol) react 12 hours.It is concentrated under reduced pressure and removes solvent, be added ethyl acetate (20mL), saturated common salt water washing (10mL x 3), organic phase is dried, filtered with anhydrous magnesium sulfate, and filtrate is concentrated under reduced pressure, and residue separates [petroleum ether/second through silica gel column chromatography Acetoacetic ester (v/v)=10/1], light yellow solid 365mg is obtained, yield: 61.3%.
1H NMR(400MHz,CDCl3)δ(ppm):8.66-8.64(m,2H),8.42-8.36(m,2H),7.78(s,1H), 7.52-7.45 (m, 3H), 7.31-7.29 (m, 3H), 7.19 (d, J=8.8Hz, 2H), 6.84 (t, J=55.2Hz, 1H), 2.86 (s,3H)；
LC-MS:(M+1) m/z=596.1.
2- difluoromethyl -6- (4- hydroxyphenoxy) (1H) -one of -8- methylquinoline -4 is passed through into implementation with corresponding material The target compound in table 5 can be prepared in the synthetic method of example 38.
Table 5
Embodiment 42:6- (4- ((6- chloropyridine -3- base) oxygroup) phenoxy group) -2- ethyl -3,7- dimethyl quinoline -4- The synthesis of base-allyl cyclopropyl -1- sulphonic acid ester
Step 1: the synthesis of the chloro- 5- of 2- (4- (2- methyl -4-nitrophenoxy) phenoxy group) pyridine
4- ((6- chloropyridine -3- base) oxygroup) phenol (5g, 22.6mmol), potassium carbonate (4.7g, 33.9mmol) are added In 100mL single port bottle, the dry n,N-Dimethylformamide of 45mL is added, after being stirred at room temperature 15 minutes, is slowly added to the fluoro- 5- of 2- Nitrotoleune (5.3g, 33.9mmol) is added and is reacted 14 hours in lower 90 DEG C of nitrogen protection.It is cooled to room temperature, crude product pours into ice In water and salt acid for adjusting pH is added to faintly acid, solid is precipitated, filtering obtains beige solid 7.2g, yield: 87.6%.
LC-MS:(M+1) m/z=357.1.
Step 2: the synthesis of 4- (4- ((6- chloropyridine -3- base) oxygroup) phenoxy group) -3- methylaniline
By the chloro- 5- of 2- (4- (2- methyl -4-nitrophenoxy) phenoxy group) pyridine (7g, 19.7mmol), ammonium chloride 250mL single port bottle is added in the mixed solution [ethanol/water (v/v)=10/1,120mL] of (1.6g, 39.3mmol) and ethyl alcohol and water In, it is slowly added to reduced iron powder (2.2g, 39.3mmol) after being warming up to reflux, is continued back flow reaction 2 hours after adding.It is down to room Iron powder is filtered to remove after temperature, ethyl alcohol is distilled off in filtrate decompression, and obtained dope adds water and with salt acid for adjusting pH, and solid is precipitated Product, filtering, obtains light yellow solid 5.3g, yield: 82.8%.
LC-MS:(M+1) m/z=327.08.
Step 3: -4 (1H) -one of 6- (4- ((6- chloropyridine -3- base) oxygen) phenoxy group) -2- ethyl -3,7- dimethyl quinoline Synthesis
Under nitrogen protection, by 4- (4- ((6- chloropyridine -3- base) oxygen) phenoxy group) -3- methylaniline (5.3g, 16.3mmol), 2- methyl -3- oxopentanoic acid methyl ester (7.6g, 48.7mmol), glacial acetic acid (1mL) and toluene (60mL) are added to In 250mL single port bottle with water segregator, it is heated to 130 DEG C, reflux water-dividing 12 hours.It is concentrated under reduced pressure and removes toluene, obtain palm fibre Color grease.It is added diphenyl ether (20mL), is heated to 250 DEG C, stir 30 minutes, the reaction is cooled to room temperatures, are slowly added into stone Oily ether (50mL), there is solid precipitation, and filtering, filter cake washs (v/v=10/1,30mL x 3) with petrol ether/ethyl acetate solution, Obtain sepia solid 3.6g, yield: 52.9%.
LC-MS:(M+1) m/z=421.1.
Step 4: 6- (4- ((6- chloropyridine -3- base) oxygroup) phenoxy group) -2- ethyl -3,7- dimethyl quinoline -4- base - The synthesis of allyl cyclopropyl -1- sulphonic acid ester
By -4 (1H) -one of 6- (4- ((6- chloropyridine -3- base) oxygen) phenoxy group) -2- ethyl -3,7- dimethyl quinoline (1g, It 2.4mmol) is dissolved in methylene chloride (20mL), under nitrogen protection, the stirring of 1mL triethylamine is added, 1- allyl is added after ten minutes Cyclopropyl -1- sulfonic acid chloride (0.64g, 3.6mmol) is stirred at room temperature 10 hours.It is concentrated under reduced pressure and removes methylene chloride, residual Object separates [petrol ether/ethyl acetate (v/v)=6/1] through silica gel column chromatography, obtains yellow solid 554mg, yield: 40.4%.
LC-MS:(M+1) m/z=565.1.
Embodiment 43:6- (4- (benzo [d] thiazol-2-yl) phenoxy group) -2- ethyl -3,7- dimethyl quinoline -4- base second The synthesis of acid esters
Step 1: the synthesis of 4- (benzo [d] thiazol-2-yl) phenol
Near amino thiophenols (3.76g, 30.00mmol) are added to the 1N of 4- trifloro methyl phenol (1.62g, 10mmol) In NaOH solution (30mL), stirred 3 days at 50 DEG C.It is cooled to room temperature, with 1N salt acid for adjusting pH to acidity, ethyl acetate extraction (50mL x 3) merges organic phase, and anhydrous magnesium sulfate dries, filters, and filtrate is concentrated under reduced pressure, and residue is separated through silica gel column chromatography [petrol ether/ethyl acetate (v/v)=3/1], obtains light yellow solid 460mg, yield: 20%.
LC-MS:(M+1) m/z=228.1.
Step 2: the synthesis of 2- (4- (2- methyl -4-nitrophenoxy) phenyl) benzo [d] thiazole
By 4- (benzo [d] thiazol-2-yl) phenol (460mg, 2.03mmol), potassium carbonate (560mg, 4.06mmol) and N, Dinethylformamide (5mL) is added in 50mL single port bottle, is heated to 65 DEG C and is stirred 2 hours.The fluoro- 5- nitro of 2- is slowly added dropwise The n,N-Dimethylformamide solution (5mL) of toluene (287mg, 1.85mmol) continues stirring 10 hours.It is cooled to room temperature, it will Mixture had solid precipitation, and filtered, filter cake is washed with water (10mL x 3), obtains down to stirring 30 minutes in ice water (50mL) Yellow solid 630mg, yield: 94%.
LC-MS:(M+1) m/z=363.2.
Step 3: the synthesis of 4- (4- (benzo [d] thiazol-2-yl) phenoxy group) -3- methylaniline
By 2- (4- (2- methyl -4-nitrophenoxy) phenyl) benzo [d] thiazole (630mg, 1.74mmol), iron powder (390mg, 6.96mmol), ethyl alcohol (20mL), water (2mL) and hydrochloric acid (0.1g, 35% aqueous solution) are added in 50mL single port bottle, Under nitrogen protection, it is heated to 90 DEG C and stirs 12 hours.After completion of the reaction, it filters, filtrate is concentrated under reduced pressure, ethyl acetate dilution is added (50mL), with saturated common salt water washing (30mL x 3), organic phase is dried, filtered with anhydrous magnesium sulfate, and filtrate is concentrated under reduced pressure, residual It stays object to separate [petrol ether/ethyl acetate (v/v)=5/1] through silica gel column chromatography, obtains light yellow solid 500mg, yield: 86%.
LC-MS:(M+1) m/z=333.2.
Step 4: -4 (1H) -one of 6- (4- (benzo [d] thiazol-2-yl) phenoxy group) -2- ethyl -3,7- dimethyl quinoline Synthesis
Under nitrogen protection, by 4- (4- (benzo [d] thiazol-2-yl) phenoxy group) -3- methylaniline (500mg, 1.50mmol), 2- methyl -3- oxopentanoic acid methyl ester (474mg, 3.00mmol), glacial acetic acid (0.1g) and toluene (15mL) are added Into the 100mL single port bottle with water segregator, it is heated to 120 DEG C, reflux water-dividing 18 hours.It is concentrated under reduced pressure and removes toluene, obtain Brown oil.It is added diphenyl ether (10mL), is heated to 255 DEG C, stir 30 minutes, the reaction is cooled to room temperatures, are slowly added into Petroleum ether (30mL) has solid precipitation, and filtering, filter cake washs (v/v=10/1,10mL x with petrol ether/ethyl acetate solution 3) beige solid 384mg, is obtained, yield: 60%.
LC-MS:(M+1) m/z=427.3.
Step 5: 6- (4- (benzo [d] thiazol-2-yl) phenoxy group) -2- ethyl -3,7- dimethyl quinoline -4- guanidine-acetic acid The synthesis of ester
By -4 (1H) -one of 6- (4- (benzo [d] thiazol-2-yl) phenoxy group) -2- ethyl -3,7- dimethyl quinoline (384mg, 0.90mmol) is dissolved in acetic anhydride (10mL), under nitrogen protection, is heated to 120 DEG C and is reacted 12 hours.It depressurizes dense Contracting removes acetic anhydride, is added ethyl acetate (20mL), saturated common salt water washing (10mL x 3), and organic phase is dry with anhydrous magnesium sulfate Dry, filtrate is concentrated under reduced pressure in filtering, and residue separates [petrol ether/ethyl acetate (v/v)=10/1] through silica gel column chromatography, obtains White solid 188mg, yield: 45%.
1H NMR(400MHz,CDCl3) δ (ppm): 8.08 (dd, J=8.6,4.1Hz, 3H), 7.99 (d, J=9.0Hz, 1H), 7.93 (s, 1H), 7.52 (s, 1H), 7.45-7.36 (m, 2H), 7.00 (d, J=8.8Hz, 2H), 3.13-3.01 (m, 2H), 2.65 (s, 3H), 2.48 (s, 3H), 2.31 (s, 3H), 1.43 (t, J=7.5Hz, 3H)；
LC-MS:(M+1) m/z=468.80.
Active testing
In following tests example, inventor has detected the compounds of this invention to evil by taking part of compounds of the invention as an example The effect of worm.
1, compound is prepared
The raw medicine that certain mass is weighed with assay balance (0.0001g) is matched with the DMF dissolution containing 1% Tween-80 emulsifier 1% mother liquor is made, is then diluted with distilled water spare.
2, test method
Leaf dipping method: being mythimna separata for examination target, i.e., naturally negative after sufficiently infiltrating appropriate maize leaf in the medical fluid prepared It is dry, it is put into the culture dish for being lined with filter paper, connects mythimna separata 3 age mid-term larva, 10/ware, be placed in 24~27 DEG C of observation ward and cultivate, Investigation result after 3d.Polypide is touched with writing brush, it is reactionless to be considered as dead worm.Experimental concentration 500mg/L.
Spray-on process: being Brown Planthopper for examination target, i.e., respectively sprays the rice seedlings for being connected to Brown Planthopper in Potter Spraying treatment under mist tower, Brown Planthopper is placed in 24~27 DEG C of observation ward and cultivates after processing, investigation result after 72h.It tests dense Spend 500mg/L.
Spray-on process: it is Tetranychus cinnabarinus, aphis craccivora for examination target, i.e., will be connected to the broadbean leaf of Tetranychus cinnabarinus and aphis craccivora respectively Piece spraying treatment under Potter spray tower, Tetranychus cinnabarinus is placed in 24~27 DEG C of observation ward and cultivates after processing, and aphis craccivora is placed in It is cultivated in 20~22 DEG C of observation ward, investigation result after 48h.Polypide is touched with writing brush, it is reactionless to be considered as dead worm.Experimental concentration 500mg/L。
Test result is as shown in table 6 and table 7.
Lethality of 6 the compounds of this invention of table to mythimna separata
Lethality of 7 the compounds of this invention of table to brown paddy plant hopper
Embodiment Lethality (%)
Embodiment 1 100
Embodiment 3 100
Embodiment 4 90
Embodiment 6 100
Embodiment 7 100
Embodiment 8 100
Embodiment 9 100
Embodiment 10 100
Embodiment 11 100
Embodiment 12 90
Embodiment 13 90
Embodiment 14 100
Embodiment 15 90
Embodiment 17 100
Embodiment 18 100
Embodiment 19 100
Embodiment 20 100
Embodiment 27 80
Embodiment 31 100
Embodiment 33 80
Embodiment 34 90
Embodiment 35 80
Embodiment 42 90
Table 6 and table 7 the result shows that, the compounds of this invention has significant effect to mythimna separata and brown paddy plant hopper.In addition, of the invention Compound has a significant effect to aphis craccivora and Tetranychus cinnabarinus under 500mg/L concentration, and lethality can reach 50% or more.
The preferred embodiment of the present invention has been described above in detail, still, during present invention is not limited to the embodiments described above Detail within the scope of the technical concept of the present invention can be with various simple variants of the technical solution of the present invention are made, this A little simple variants all belong to the scope of protection of the present invention.

Claims (10)

1. a kind of compound is stereoisomer, the nitrogen oxidation of the compound as shown in formula (A) compound represented or formula (A) Object and its acceptable salt:
Wherein:
R1For hydrogen, C1-6Alkyl, halogenated C1-6Alkyl, C2-6Alkenyl or C1-6Alkoxy；
R2For hydrogen or C1-6Alkyl；
R3For hydrogen, C1-6Alkyl, amino-C1-6Alkylidene-, C6-14Aryl, C6-14Aryl-C1-6Alkylidene-,-(C=O) R6Or- SO2R7；Wherein, R3Optionally X is selected from by 1,2,3,4,5 or 61Substituent group replace；
Wherein, R6For C1-6Alkyl, C2-6Alkenyl, C2-6Alkynyl, C3-10Naphthenic base, C6-14Aryl, C6-14Aryl-C1-6Alkylidene-, 3- 10 circle heterocyclic ring bases, 5-10 unit's heteroaryl ,-OR8Or-NRnRm；
Wherein, R7For C1-6Alkyl, C3-10Naphthenic base, C6-14Aryl, 5-10 unit's heteroaryl or-NRnRm；
Wherein, R8For C1-6Alkyl, C2-6Alkenyl, C2-6Alkynyl, C3-10Naphthenic base, 3-10 circle heterocyclic ring base, 5-10 unit's heteroaryl, C6-14 Aryl or C6-14Aryl-C1-6Alkylidene-；
Wherein, each RnAnd RmIt independently is hydrogen, C1-6Alkyl, C3-10Naphthenic base, C6-14Aryl or 5-10 unit's heteroaryl；
Or Rn、Rm3-10 circle heterocyclic ring base is formed with connected nitrogen-atoms；
Wherein, X1For halogen, nitro, cyano, oxo (=O), hydroxyl, amino, C1-6Alkyl, C2-6Alkenyl, C2-6It is alkynyl, halogenated C1-6Alkyl, halogenated C2-6Alkenyl, halogenated C2-6Alkynyl, C1-6Alkoxy, halogenated C1-6Alkoxy, C3-8Naphthenic base, C6-14Aryl, halogen For C6-14Aryl, C6-14Aryloxy, 5-10 unit's heteroaryl or halogenated 5-10 unit's heteroaryl；
Or X1For following subformula:
Wherein, each RxIt independently is halogen or C1-6Alkyl；
P is 0,1,2,3 or 4；
Ay is C6-14Aryl or 5-10 unit's heteroaryl；The wherein C6-14Aryl or 5-10 unit's heteroaryl optionally by halogen, C1-6Alkyl or C1-6Alkoxy replaces；
R4aFor hydrogen, halogen, cyano, C1-6Alkyl, halogenated C1-6Alkyl, C1-6Alkoxy, C1-6Alkyl-(C=O)-, C1-6Alkoxy- (C=O)-or C1-6Alkyl-(C=O)-O-；
R4bFor hydrogen, halogen, C1-6Alkyl, halogenated C1-6Alkyl, C1-6Alkoxy, C1-6Alkyl-(C=O)-, C1-6Alkoxy-(C= O)-or C1-6Alkyl-(C=O)-O-；
R4cFor hydrogen, halogen, C1-6Alkyl, halogenated C1-6Alkyl or C1-6Alkoxy；
Condition are as follows: R4a、R4bAnd R4cIt is not simultaneously hydrogen；
Q is 0,1,2,3 or 4；
Each R5It independently is halogen, nitro, cyano, C1-6Alkyl, halogenated C1-6Alkyl, C1-6Alkoxy or halogenated C1-6Alkoxy；
Y is key ,-O- ,-S- ,-O (CR9R10)n-L1Or-NR11-L2-；
Wherein, R9And R10It is each independently hydrogen or C1-6Alkyl；
Or R9、R10C=O is formed with the carbon atom being connected；
N is 1,2 or 3；
L1Linear chain or branched chain for key or containing 1,2,3,4,5 or 6 carbon atom；
R11For hydrogen or C1-6Alkyl；
L2For key, C=O or SO2；
Z is C6-14Aryl or 5-10 unit's heteroaryl；Wherein, Z is optionally selected from X by 1,2,3,4,5,6,7 or 82Substituent group take Generation；
Wherein, X2For halogen, nitro, cyano, hydroxyl, amino, C1-6Alkyl, halogenated C1-6Alkyl, C2-6Alkenyl, C1-6Alkoxy, halogen For C1-6Alkoxy, C6-14Aryl or halogenated C6-14Aryl；
Condition are as follows:
1) formula (A) compound represented does not include compound 2,3- dimethyl -5- (trifluoromethyl) -6- (4- (4- (trifluoromethyl) Phenoxy group) phenoxy group) quinolyl-4 acetic acid esters, 2,3- dimethyl -7- (trifluoromethyl) -6- (4- (4- (trifluoromethyl) benzene oxygen Base) phenoxy group) quinolyl-4 acetic acid esters, 2,3- dimethyl -5- (trifluoromethyl) -6- ((4'- (trifluoromethyl)-[1,1'- connection Benzene] -4- base) oxygroup) quinolyl-4 acetic acid esters and 2,3- dimethyl -7- (trifluoromethyl) -6- ((4'- (trifluoromethyl)-[1, 1'- biphenyl] -4- base) oxygroup) quinolyl-4 acetic acid esters；
2) as R in formula (A) compound represented3For-(C=O) R6, R6For-OR8, R8For C1-4Alkyl, R1For C1-4Alkyl, R2For C1-4Alkyl, R4cFor hydrogen, when q 0, Y are O, Z is not 5- trifluoromethyl -2- pyridyl group or 3- halogen -5- trifluoromethyl -2- pyridine Base.
2. compound according to claim 1, wherein
R1For hydrogen, C1-4Alkyl, halogenated C1-4Alkyl, C2-4Alkenyl or C1-4Alkoxy；
R2For hydrogen or C1-4Alkyl；
R3For hydrogen, C1-4Alkyl, amino-C1-4Alkylidene-, C6-10Aryl, C6-10Aryl-C1-4Alkylidene-,-(C=O) R6Or- SO2R7；Wherein, R3Optionally X is selected from by 1,2,3,4,5 or 61Substituent group replace；
Wherein, R6For C1-4Alkyl, C2-4Alkenyl, C2-4Alkynyl, C3-6Naphthenic base, C6-10Aryl, C6-10Aryl-C1-4Alkylidene-, 3- 10 circle heterocyclic ring bases, 5-10 unit's heteroaryl ,-OR8Or-NRnRm；
Wherein, R7For C1-4Alkyl, C3-6Naphthenic base, C6-10Aryl, 5-10 unit's heteroaryl or-NRnRm；
Wherein, R8For C1-4Alkyl, C2-4Alkenyl, C2-4Alkynyl, C3-6Naphthenic base, 3-10 circle heterocyclic ring base, 5-10 unit's heteroaryl, C6-10 Aryl or C6-10Aryl-C1-4Alkylidene-；
Wherein, each RnAnd RmIt independently is hydrogen, C1-4Alkyl, C3-6Naphthenic base, C6-10Aryl or 5-10 unit's heteroaryl；
Or Rn、Rm3-10 circle heterocyclic ring base is formed with connected nitrogen-atoms；
Wherein, X1For halogen, nitro, cyano, oxo (=O), hydroxyl, amino, C1-4Alkyl, C2-4Alkenyl, C2-4It is alkynyl, halogenated C1-4Alkyl, halogenated C2-4Alkenyl, halogenated C2-4Alkynyl, C1-4Alkoxy, halogenated C1-4Alkoxy, C3-6Naphthenic base, C6-10Aryl, halogen For C6-10Aryl, C6-10Aryloxy, 5-10 unit's heteroaryl or halogenated 5-10 unit's heteroaryl；
Or X1For following subformula:
Wherein, each RxIt independently is halogen or C1-4Alkyl；
P is 0,1,2,3 or 4；
Ay is C6-12Aryl or 5-10 unit's heteroaryl；The wherein C6-12Aryl or 5-10 unit's heteroaryl optionally by halogen, C1-4Alkyl or C1-4Alkoxy replaces；
R4aFor hydrogen, halogen, cyano, C1-4Alkyl, halogenated C1-4Alkyl, C1-4Alkoxy, C1-4Alkyl-(C=O)-, C1-4Alkoxy- (C=O)-or C1-4Alkyl-(C=O)-O-；
R4bFor hydrogen, halogen, C1-4Alkyl, halogenated C1-4Alkyl, C1-4Alkoxy, C1-4Alkyl-(C=O)-, C1-4Alkoxy-(C= O)-or C1-4Alkyl-(C=O)-O-；
R4cFor hydrogen, halogen, C1-4Alkyl, halogenated C1-4Alkyl or C1-4Alkoxy.
3. compound according to claim 1 or 2, wherein
R1For hydrogen, C1-4Alkyl or halogenated C1-4Alkyl；
R2For hydrogen or C1-4Alkyl；
R3For hydrogen, C1-4Alkyl, amino-C1-4Alkylidene-, C6-10Aryl, C6-10Aryl-C1-4Alkylidene-,-(C=O) R6Or- SO2R7；Wherein, R3Optionally X is selected from by 1,2,3,4,5 or 61Substituent group replace；
Wherein, R6For C1-4Alkyl, C2-4Alkenyl, C3-6Naphthenic base, C6-10Aryl, C6-10Aryl-C1-4Alkylidene-, 5-10 member heteroaryl Base ,-OR8Or-NRnRm；
Wherein, R7For C1-4Alkyl, C3-6Naphthenic base, C6-10Aryl, 5-10 unit's heteroaryl or-NRnRm；
Wherein, R8For C1-4Alkyl or C6-10Aryl；
Wherein, each RnAnd RmIt independently is hydrogen, C1-4Alkyl or C3-6Naphthenic base；
Or Rn、Rm3-10 circle heterocyclic ring base is formed with connected nitrogen-atoms；
Wherein, X1For halogen, nitro, cyano, oxo (=O), hydroxyl, amino, C1-4Alkyl, C2-4Alkenyl, C2-4It is alkynyl, halogenated C1-4Alkyl, halogenated C2-4Alkenyl, halogenated C2-4Alkynyl, C1-4Alkoxy, halogenated C1-4Alkoxy, C3-6Naphthenic base, C6-10Aryl, halogen For C6-10Aryl, C6-10Aryloxy, 5-10 unit's heteroaryl or halogenated 5-10 unit's heteroaryl；
Or X1For following subformula:
Wherein, each RxIt independently is halogen or C1-4Alkyl；
P is 0,1,2,3 or 4；
Ay is C6-10Aryl or 5-10 unit's heteroaryl；The wherein C6-10Aryl or 5-10 unit's heteroaryl optionally by halogen, C1-4Alkyl or C1-4Alkoxy replaces；
R4aFor hydrogen, halogen, cyano, C1-4Alkyl, halogenated C1-4Alkyl, C1-4Alkoxy or C1-4Alkoxy-(C=O)-；
R4bFor hydrogen, halogen, C1-4Alkyl, halogenated C1-4Alkyl, C1-4Alkoxy or C1-4Alkoxy-(C=O)-；
R4cFor hydrogen, halogen, C1-4Alkyl or halogenated C1-4Alkyl.
4. compound according to claim 3, wherein
R1For hydrogen ,-CH3、-CH2CH3、-CH(CH3)2、-C(CH3)3、-CHF2Or-CF3；
R2For hydrogen ,-CH3、-CH2CH3Or-C (CH3)3；
R3For following subformula:
R4aFor hydrogen, fluorine, chlorine, bromine, cyano ,-CH3、-CH2CH3、-CF3、-OCH3Or-C (=O) OCH3；
R4bFor hydrogen, fluorine, chlorine, bromine ,-CH3、-CH2CH3、-CHF2、-CF3、-OCH3Or-C (=O) OCH3；
R4cFor hydrogen, fluorine, chlorine, bromine ,-CH3Or-CF3。
5. compound according to claim 1, wherein
Q is 0,1,2,3 or 4；
Each R5It independently is halogen, nitro, cyano, C1-4Alkyl, halogenated C1-4Alkyl, C1-4Alkoxy or halogenated C1-4Alkoxy；
Y is key ,-O- ,-S- ,-O (CR9R10)n-L1Or-NR11-L2-；
Wherein, R9And R10It is each independently hydrogen or C1-4Alkyl；
Or R9、R10C=O is formed with the carbon atom being connected；
N is 1,2 or 3；
L1Linear chain or branched chain for key or containing 1,2,3,4,5 or 6 carbon atom；
R11For hydrogen or C1-4Alkyl；
L2For key, C=O or SO2；
Z is C6-10Aryl or 5-10 unit's heteroaryl；Wherein, Z is optionally selected from X by 1,2,3,4,5,6,7 or 82Substituent group take Generation；
Wherein, X2For halogen, nitro, cyano, hydroxyl, amino, C1-4Alkyl, halogenated C1-4Alkyl, C2-4Alkenyl, C1-4Alkoxy, halogen For C1-4Alkoxy, C6-10Aryl or halogenated C6-10Aryl.
6. compound according to claim 1 or 5, wherein
Q is 0,1,2,3 or 4；
Each R5It independently is halogen or C1-4Alkyl；
Y is key ,-O- ,-S- ,-O (CR9R10)n-L1Or-NR11-L2-；
Wherein, R9And R10It is each independently hydrogen；
Or R9、R10C=O is formed with the carbon atom being connected；
N is 1 or 2；
L1Linear chain or branched chain for key or containing 1,2 or 3 carbon atom；
R11For hydrogen；
L2For key, C=O or SO2；
Z is C6-10Aryl or 5-10 unit's heteroaryl；Wherein, Z is optionally selected from X by 1,2,3,4,5,6,7 or 82Substituent group take Generation；
Wherein, X2For halogen, nitro, cyano, hydroxyl, amino, C1-4Alkyl, halogenated C1-4Alkyl, C2-4Alkenyl, C1-4Alkoxy, halogen For C1-4Alkoxy, C6-10Aryl or halogenated C6-10Aryl.
7. compound according to claim 6, wherein
Each R5It independently is fluorine, chlorine, bromine ,-CH3Or-CH2CH3；
Y is key ,-O- ,-O (C=O)-,-O (C=O)-CH=CH- or-NH- (C=O)-；
Z is following subformula:
8. a kind of compound, the compound with one of following structure or the alloisomerism with one of following structural compounds Body, nitrogen oxides and its acceptable salt:
9. a kind of composition is further included and is subjected in Pesticide Science comprising compound described in claim 1-8 any one Surfactant and carrier.
10. compound described in claim 1-8 any one or composition as claimed in claim 9 are in agricultural for preventing and treating The application of plant insect.
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CN1993328A (en) * 2004-08-04 2007-07-04 明治制果株式会社 Quinoline derivative and insecticide containing same as active constituent
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CN110950770B (en) * 2019-12-10 2023-04-07 珠海润都制药股份有限公司 Synthesis method of lacosamide

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