CN113200976B - 3-aryl azabicyclo derivatives, preparation thereof and nematicidal application thereof - Google Patents

3-aryl azabicyclo derivatives, preparation thereof and nematicidal application thereof Download PDF

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CN113200976B
CN113200976B CN202110535888.9A CN202110535888A CN113200976B CN 113200976 B CN113200976 B CN 113200976B CN 202110535888 A CN202110535888 A CN 202110535888A CN 113200976 B CN113200976 B CN 113200976B
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CN113200976A (en
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宋恭华
卢奥运
王佳毅
李晖
郑一汀
李涛
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East China University of Science and Technology
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    • 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
    • C07D417/04—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 directly linked by a ring-member-to-ring-member bond
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • 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
    • 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
    • A01N43/82—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 three ring hetero atoms
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • 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
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
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    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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    • 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
    • C07D413/04—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 directly linked by a ring-member-to-ring-member bond
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    • 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
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

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Abstract

The invention relates to preparation of a 3-aryl azabicyclo derivative and application thereof in killing nematodes. Specifically, the invention discloses a compound with a structure shown in formula (I) or a composition thereof, and application of an optical isomer, a cis-trans isomer and an agriculturally and pharmaceutically acceptable salt thereof in the field of nematicidal.

Description

3-aryl azabicyclo derivatives, preparation thereof and nematicidal application thereof
Technical Field
The invention belongs to the field of pesticides. In particular, the invention relates to a 3-aryl azabicyclo derivative, a preparation method thereof and application thereof in killing nematodes.
Technical Field
Plant parasitic nematodes have been developed worldwide as major pathogens of plants in agriculture and forestry, including commercial crops such as potatoes, soybeans, tomatoes, and trees such as olive trees, pines, and the like. Crop yield losses of about 12-15% per year from plant parasitic nematode infestation, global direct agronomic losses of $ 1570 billion, due to the endoparasitic nature of plant parasitic nematodes, most of their life cycles are completed in the host plant, protected by the host plant tissue, and thus difficult to control.
To date, more than 4100 plant parasitic nematodes have been reported, with the most devastating being obligate biotrophic root-knot nematodes (melodogyne spp.). One tenth of the vegetable production worldwide is affected by nematode infestation, wherein 50% of these losses are caused by root-knot nematodes, the damage of which starts with the infestation of 2-instar larvae (J2) on the root elongation zone of the plant, J2 releases cell wall lyase through the stylet into the epidermis of the host plant root, which migrates internally through the cortex to the apical area to parasitize selected vascular bundle tissue cells, the complex parasitic relationship between them and the host cells is regulated by root-knot nematode secretions, which in turn affects the development and gene expression of the host cells, so that the host cells evolve into larger multinucleated cells, i.e. Giant cells, which become the single nutrient donor of the nematodes. With the development of giant cells, the adjacent vascular bundles and cortical cells are proliferated and enlarged to form root nodules.
Pine wood nematodes (Bursaphelenchus xylophilus) originally existed as species of ecological balance in pine trees in North America, have now developed into invasive species in forest ecosystems in Japan, the peninsula Korea and east Asia regions of China, and are further infecting Spanish and Portugal Europe, where more than 100 million hectares of pine trees die each year due to the harm of pine wood nematodes. Pine wood nematode is taken as a parasitic nematode in a migratory plant to cause pine wilt, which seriously damages the forest ecosystem in the far east Asia region, can be carried by a medium insect, namely Monochamus spp to spread from dead pine to healthy pine, has the characteristics of herbivory and phagocytosis unlike other nematodes in the same genus, draws nutrition from parenchyma cells of the xylem of the pine through a resin pipeline to further cause the pine to wither, and starts to feed Botrytis cinerea (Botrytis cinerea) parasitizing on the pine after the pine dies
In 1881, carbon disulfide (CS) 2 ) The first product to be considered as nematicidal, in the middle of the first 20 th century, methyl bromide, chloropicrin (CP), D-D mixtures (1, 3-D and 1,2-D, shell 1942), dibromochloropropane (DBCP, dour 1955), 1, 2-dibromoethylene (EDB, dow 1946) and other halogenated hydrocarbon fumigants were introduced for nematode control, in 1952, dazomet (Mylone) was introduced by Stauffer for nematode control, in 1955, stauffer developed products including metam (Vapam) and nematicide (Sassen), which decompose in moist soil, releasing methyl isothiocyanate, hydrogen sulfide and formaldehyde with fumigating effect, thereby achieving nematicidal purposes. At the beginning of the 20 th century and the 60 th century, organophosphorus and carbamate nematicides gradually replaced fumigants, and efficient non-fumigant nematicides represented by fenamiphos (Ethoprophos), fosthiazate (1991), oxamyl (Oxamyl, 1972) and aldicarb (Temik, 1962) were proposed, and the nematicides mainly act on acetylcholinesterase (AChE) in the nervous system of nematodes, so that nerve conduction of nematodes is hindered, physiological activity of the nematodes is disturbed, and the nematodes die.
Due to environmental pressure, high toxicity, continuous improvement of nematode resistance caused by long-term use, some influences on non-target biological neurotoxicity and the like, some nematicides are gradually eliminated in the market, even some nematicides are forbidden, the variety of currently selected nematicides is few, and the development of novel nematicides is indispensable.
Disclosure of Invention
The invention aims to provide a preparation method of a 3-aryl azabicyclo derivative and application of the derivative in killing nematodes, in particular application in the field of plant parasitic nematodes, so as to play a role in protecting plants.
The nematicidal compositions described herein comprise an effective amount of a compound or mixture of compounds having any of the formulae described herein, for example the compounds shown below.
In the first aspect of the invention, the compound shown in the general formula I, or the optical isomer, the cis-trans isomer and the agriculturally and pharmaceutically acceptable salt thereof are provided.
Figure BDA0003069814030000021
Wherein the content of the first and second substances,
r is hydrogen, substituted or unsubstituted C1-C15 alkyl, substituted or unsubstituted C3-C7 cycloalkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C15 alkoxy, substituted or unsubstituted 5-or 6-membered heteroaromatic ring, carbonyl-C6-C10 aryl-C1-C15 alkyl, C1-C15 alkoxycarbonyl, C6-C10 arylC 1-C15 alkoxycarbonyl; the substituted means substituted with one or more substituents selected from the group consisting of: halogen, cyano, nitro, hydroxyl, amino, C1-C6 alkyl, halogenated C1-C6 alkyl, C1-C6 alkoxy, carboxyl and C6-C10 aryl;
X 1 is CH = CH or absent, X 2 Is CH = CH or absent, and when X is present 1 When CH = CH, X is absent 2 (ii) a When X is 2 Is CH = CH, X is absent 1 ；
A is N, S or CH;
b is N or C;
d is CH, N, O or S;
e is C, N, O or CH;
ar is a benzene ring, a naphthalene ring, a 5-6 membered heteroaromatic ring or an 8-12 membered heteroaromatic bicyclic ring system; r 1 Is a substituent on Ar in a number of 0, 1,2, 3 or 4, each R 1 Each independently selected from: C1-C6 alkyl, C1-C6 alkoxy, halogen, halogenated C1-C6 alkyl, halogenated C1-C6 alkoxy, cyano, nitro, C6-C10 aryl, 5-or 6-membered heteroaryl, or-OAr 1 (ii) a It is composed ofMiddle Ar 1 Is a C6-C10 aryl, 5-or 6-membered heteroaryl or 8-12 membered heteroaromatic bicyclic ring system; wherein the C6-C10 aryl, 5-or 6-membered heteroaryl is optionally substituted with 1,2, 3 or 4 substituents selected from the group consisting of: halogen, cyano, nitro, hydroxyl, amino, C1-C6 alkyl, halogenated C1-C6 alkyl and C1-C6 alkoxy.
In another preferred embodiment, R is a substituted or unsubstituted C1-C4 alkyl group or a substituted or unsubstituted C1-C4 alkoxycarbonyl group; said substituted means substituted with 1,2 or 3 substituents selected from the group consisting of: halogen, cyano, nitro, hydroxyl, amino, C1-C4 alkyl, halogenated C1-C4 alkyl, C1-C4 alkoxy, carboxyl and phenyl.
In another preferred embodiment, when D is S or O, B is C, A is N, E is N or C (H), X 1 And X 2 Is absent.
In another preferred embodiment, when D is S, B is C, A is N, E is N or C (H), X 1 And X 2 Is absent.
In another preferred embodiment, when D is O, B is C, A is N, E is N, X is 1 And X 2 Is absent.
In another preferred embodiment, when D is N, B is C, A is S or N, E is CH or O, X 1 And X 2 Is absent.
In another preferred embodiment, when D is N, B is C, A is S, E is CH, X is 1 And X 2 Is absent.
In another preferred embodiment, when D is N, B is C, A is N, E is O, X 1 And X 2 Is absent.
In another preferred embodiment, when D is CH or N, B is N, A is CH or N, E is C, X is 2 Is CH = CH.
In another preferred embodiment, when D is C, B is N, A is N, and E is CH, X is 1 Is CH = CH.
In another preferred embodiment, when D is CH or N, B is N, A is CH or N, E is CH, X is 1 And X 2 Is absent.
In another preferred embodiment, when D is N, B is N, A is CH, and E is CH, X is 1 And X 2 Is absent.
In another preferred embodiment, when D is N, B is N, a is CH, and E is C, X is CH = CH.
In another preferred example, when D is CH, B is N, a is N, E is C, X is CH = CH.
In another preferred embodiment, when D is CH, B is N, A is N, E is CH, X 1 And X 2 Is absent.
In another preferred embodiment, the compound has the structure shown below,
Figure BDA0003069814030000031
wherein Ar is as defined in claim 1, optionally having 1,2 or 3 substituents R 1 ；R、R 1 Is defined as in claim 1.
In another preferred embodiment, ar is a phenyl ring, a naphthyl ring, a 5-6 membered heteroaromatic ring or an 8-10 membered heteroaromatic bicyclic ring system, optionally with 1,2 or 3 substituents R 1 ；
In each formula, each R 1 Each independently selected from: C1-C6 alkyl, C1-C4 alkoxy, fluoro, chloro, bromo, haloC 1-C4 alkyl, haloC 1-C4 alkoxy, cyano, nitro, phenyl, 5-or 6-membered heteroaryl, -O-phenyl, -O-5-or 6-membered heteroaryl; wherein phenyl, 5-or 6-membered heteroaryl is optionally substituted with 1 or 2 substituents selected from the group consisting of: halogen, cyano, nitro, hydroxyl, amino, C1-C4 alkyl, halogenated C1-C4 alkyl and C1-C4 alkoxy.
In another preferred embodiment, the compound has a structure shown as one of 4aa-52 ac.
In a second aspect of the invention, there is provided a pesticidal composition comprising a compound of the first aspect or an agriculturally pharmaceutically acceptable salt thereof; and an agriculturally pharmaceutically acceptable carrier.
In a third aspect of the invention, there is provided a compound of the first aspect or an agriculturally acceptable salt thereof, or a pesticidal composition of the second aspect for use in killing or preventing nematodes; or for the preparation of a medicament for killing or preventing nematodes.
In a fourth aspect of the invention there is provided a method of killing or preventing nematodes including applying a compound of the first aspect or an agriculturally acceptable salt thereof or a pesticidal composition of the second aspect to a plant suffering from or likely to suffer from a pest infestation or to the soil or environment surrounding the plant.
The present invention provides a method of killing or preventing nematodes comprising applying to the soil or environment of a plant suffering or likely to suffer from a pest, or surrounding thereof, an azabicyclo derivative or an agriculturally acceptable salt thereof according to the first aspect or a composition according to the second aspect.
In another preferred embodiment, the azabicyclo derivative or an agriculturally pharmaceutically acceptable salt thereof or the pesticidal composition is applied at a concentration of 0.05 to 200ppm; preferably, 0.1 to 100ppm; more preferably, it is 0.5 to 50ppm.
In another preferred embodiment, the nematodes include, but are not limited to, bursaphelenchus xylophilus, root knot nematode, cyst nematode of beet, kiyota solani, cyst nematode of soybean, phoma Ipomoeae, sematoda, and Aphelenchoides oryzae.
It is to be understood that within the scope of the present invention, the above-described features of the present invention and those specifically described below (e.g., in the examples) may be combined with each other to form new or preferred embodiments. Not to be reiterated herein, but to the extent of space.
Detailed Description
The present inventors have made extensive and intensive studies and, as a result, have synthesized a novel class of azabicyclic derivatives having a novel structure for the first time, which have excellent nematicidal activity.
Basic definition
The term "C1-C15 alkyl" refers to a straight or branched chain alkyl group having 1 to 15 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, 1-butyl, 2-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, or the like. C1-C6 alkyl groups may be preferred.
The term "C1-C15 alkoxy" refers to a straight or branched chain alkyl group having 1 to 15 carbon atoms, such as methoxy, ethoxy, n-propoxy, isopropoxy, 1-butoxy, 2-butoxy, pentyloxy, hexyloxy, heptyloxy, octyloxy, nonyloxy, decyloxy or the like. C1-C6 alkyl groups may be preferred.
The term "C2-C6 alkenyl" means a straight or branched chain alkenyl group having 2 to 6 carbon atoms, such as ethenyl, n-propenyl, isopropenyl, 1-butenyl, 2-butenyl, pentenyl, hexenyl, or the like. C2-C4 alkenyl groups may be preferred.
The term "C2 to C6 alkynyl" means a straight or branched alkynyl group having 2 to 6 carbon atoms, such as ethynyl, n-propynyl, isopropynyl, 1-butynyl, 2-butynyl, pentynyl, hexynyl or the like. C2-C4 alkynyl may be preferred.
The term "C3-C7 cycloalkyl" refers to a cyclic alkyl group having 3-7 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl.
The term "ring" or "ring system" refers to a carbocyclic or heterocyclic ring.
The term "heterocyclic ring" means that at least one of the atoms forming the backbone of said heterocyclic ring is other than carbon, is nitrogen, oxygen or sulfur, and the heterocyclic ring is a saturated or partially unsaturated non-aromatic heterocyclic ring, preferably the number of heteroatoms is 1,2, 3 or 4.
The term "5-or 6-membered heteroaromatic ring" refers to a five-or six-membered ring containing one or more heteroatoms selected from carbon, nitrogen, oxygen or sulfur, for example, phenyl, pyridyl, furyl, thienyl, thiazolyl, pyrrolyl, imidazolyl, pyrazolyl, pyrimidinyl, oxazolyl, piperazinyl, triazinyl, thiadiazolyl, oxadiazolyl, triazolyl and the like.
The term "8-12 membered heteroaromatic bicyclic ring system" may be selected from: naphthyl, benzofuranyl, quinolinyl, indolyl, benzothiophene, isoquinolinyl, benzothiophene, benzothiazole, benzopyrazolyl, benzimidazole, benzoxazole, benzo- [1,3] -dioxolyl, and the like.
The term "halogen" is fluorine, chlorine, bromine, iodine. The 'halo' is fluoro, chloro, bromo or iodo.
The term "active substance according to the invention" or "active compound according to the invention" means a compound according to the invention or an agriculturally pharmaceutically acceptable salt thereof.
The agriculturally pharmaceutically acceptable salts may include inorganic salts, organic acid salts, basic amino acids, or salts of acidic amino acids. Inorganic acid salts in the present invention include, for example: hydrochloric acid, hydroboric acid, nitric acid, sulfuric acid, or phosphoric acid. Organic acids in the present invention include, for example: lactic acid, formic acid, acetic acid (i.e., acetic acid), trifluoroacetic acid, fumaric acid, oxalic acid, maleic acid, citric acid, succinic acid, malic acid, methanesulfonic acid, benzenesulfonic acid, or p-toluenesulfonic acid. Acidic amino acids include, for example: glycine, aspartic acid, or glutamic acid.
The compounds of the invention are particularly effective against plant parasitic nematodes.
Nematicide combinations comprising the active substances according to the invention.
The active substances according to the invention can be prepared in a customary manner to give pesticide compositions. The active compounds can be formulated in conventional preparations such as solutions, emulsions, suspensions, powders, foams, pastes, granules, aerosols and the like.
These formulations can be produced by known methods, for example by mixing the active compounds with extenders, that is, liquid or liquefied gas or solid diluents or carriers, and optionally surfactants, that is, emulsifiers and/or dispersants and/or foam formers. Organic solvents may also be used as adjuvants, for example when water is used as extender.
When a liquid solvent is used as the diluent or carrier, it is basically suitable, for example: aromatic hydrocarbons such as xylene, toluene or alkylnaphthalene; chlorinated aromatic or chlorinated aliphatic hydrocarbons, such as chlorobenzene, vinyl chloride or dichloromethane; aliphatic hydrocarbons, such as cyclohexane or paraffins, such as mineral oil fractions; alcohols, such as ethanol or ethylene glycol and their ethers and lipids; ketones, such as acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone; or less commonly used polar solvents such as dimethylformamide and dimethylsulfoxide, and water.
By a diluent or carrier for liquefied gases is meant a liquid which will become gaseous at ambient temperature and pressure, for example aerosol propellants such as halogenated hydrocarbons as well as butane, propane, nitrogen and carbon dioxide.
Solid carriers can be prepared from ground natural minerals, such as kaolin, clay, talc, quartz, attapulgite, montmorillonite or kieselguhr, and ground synthetic minerals, such as highly dispersed silicic acid, alumina and silicates. Solid carriers for granules are ground and classified natural marble, such as calcite, marble, pumice, sepiolite and dolomite, as well as synthetic granules of inorganic and organic meals, and granules of organic materials, such as sawdust, coconut shells, corn cobs and tobacco stalks, etc.
Nonionic and anionic emulsifying trains may be used as emulsifiers and/or foam formers. Such as polyoxyethylene-fatty acid esters, polyoxyethylene-fatty alcohol ethers, such as alkylaryl polyethylene glycol ethers, alkyl sulfonates, alkyl sulfates, aryl sulfonates and albumin hydrolysates. Dispersants include, for example, lignin sulfite waste liquor and methyl cellulose.
Binders such as carboxymethylcellulose and natural and synthetic polymers in the form of powders, granules or emulsions, for example gum arabic, polyvinyl alcohol and polyvinyl acetate, can be used in the formulations.
Colorants such as inorganic dyes, e.g., iron oxide, cobalt oxide and prussian blue; organic dyes, such as organic dyes, e.g., azo dyes or metallotitanyl cyanine dyes; and with trace nutrients such as salts of iron, manganese, boron, copper, cobalt, aluminum, and zinc, and the like.
These formulations generally contain from 0.001 to 99.99% by weight, preferably from 0.01 to 99.9% by weight, more preferably from 0.05 to 90% by weight, of the active compounds according to the invention, based on the pesticide composition. The concentration of the active compound in the dosage form prepared from commercial preparations for use can vary within wide limits. The concentration of the active compound in the dosage form to be used may be from 0.0000001 to 100% (g/v), preferably between 0.0001 and 1% (g/v).
The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. The experimental procedures, in which specific conditions are not noted in the following examples, are generally carried out under conventional conditions or conditions recommended by the manufacturers. Unless otherwise indicated, percentages and parts are by weight.
The invention provides a preparation method of an azabicyclo derivative, which comprises the following steps:
reacting compound A1 with compound A2 in inert solvent (such as acetonitrile, methanol, isopropanol, ethanol, DMF, etc.) to obtain compound A3
Figure BDA0003069814030000061
Wherein R and Ar are as defined above.
Or the method comprises the steps of:
(1) Reacting compound B1 with compound B2 in an inert solvent (e.g. acetonitrile, methanol, isopropanol, ethanol, N-dimethylformamide, N-dimethylacetamide, water, toluene, dimethylsulfoxide, etc.) to give compound B3;
(2) Compound B4 and compound B5 are reacted in an inert solvent (e.g., acetonitrile, methanol, isopropanol, ethanol, N-dimethylformamide, N-dimethylacetamide, water, toluene, dimethylsulfoxide, etc.) to give compound B3.
Figure BDA0003069814030000062
Wherein R and Ar are as defined above.
Or the method comprises the steps of: reacting compound C1 with compound C2 in an inert solvent (such as dichloromethane, ethyl acetate, tetrahydrofuran, N-dimethylformamide, dioxane, dichloroethane, chloroform, toluene, xylene, dimethyl sulfoxide, etc.) to obtain compound C3;
Figure BDA0003069814030000063
wherein R and Ar are as defined above.
Or the method comprises the steps of: reacting compound D1 with compound C2 in an inert solvent (such as dichloromethane, ethyl acetate, tetrahydrofuran, N-dimethylformamide, dioxane, dichloroethane, chloroform, toluene, xylene, dimethyl sulfoxide, etc.) to obtain compound D3;
Figure BDA0003069814030000071
wherein R and Ar are as defined above.
Or the method comprises the steps of: reacting compound D1 and compound C2 with lawson's reagent in an inert solvent (e.g., dichloromethane, ethyl acetate, tetrahydrofuran, N-dimethylformamide, dioxane, dichloroethane, chloroform, toluene, xylene, dimethylsulfoxide, etc.) to give compound E3;
Figure BDA0003069814030000072
wherein R and Ar are as defined above.
Or the method comprises the steps of: reacting the compound F1 with the compound F2 in an inert solvent (such as dichloromethane, ethyl acetate, tetrahydrofuran, N-dimethylformamide, dioxane, dichloroethane, chloroform, toluene, xylene, dimethyl sulfoxide, etc.) under the condition of alkalinity (such as triethylamine, potassium carbonate, sodium carbonate, potassium hydroxide, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydride, etc.) to obtain a compound F3
Figure BDA0003069814030000073
Wherein R and Ar are as defined above.
Or the method comprises the steps of: reacting the compound F1 with the compound G2 in an inert solvent (such as dichloromethane, ethyl acetate, tetrahydrofuran, N-dimethylformamide, dioxane, dichloroethane, chloroform, toluene, xylene, dimethyl sulfoxide, etc.) under the condition of alkalinity (such as triethylamine, potassium carbonate, sodium carbonate, potassium hydroxide, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydride, etc.) to obtain a compound G3
Figure BDA0003069814030000074
Wherein R and Ar are as defined above.
Or the method comprises the steps of: reacting compound F1 with compound H2 in an inert solvent (such as dichloromethane, ethyl acetate, tetrahydrofuran, N-dimethylformamide, dioxane, dichloroethane, chloroform, toluene, xylene, dimethyl sulfoxide, etc.) under basic conditions (such as triethylamine, potassium carbonate, sodium carbonate, potassium hydroxide, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydride, etc.) to obtain compounds H3 and H4
Figure BDA0003069814030000081
In the formula, R and R 1 The definition is the same as before.
Or the method comprises the steps of: reacting compound F1 with compound I2 in an inert solvent (such as dichloromethane, ethyl acetate, tetrahydrofuran, N-dimethylformamide, dioxane, dichloroethane, chloroform, toluene, xylene, dimethyl sulfoxide, etc.) under basic conditions (such as triethylamine, potassium carbonate, sodium carbonate, potassium hydroxide, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydride, etc.) to obtain compounds I3 and I4;
Figure BDA0003069814030000082
in the formula, R and R 1 The definition is the same as before.
The following more specifically describes the preparation of the compounds of the present invention, but these specific methods do not set any limit to the present invention. The compounds of the present invention may also be conveniently prepared by optionally combining various synthetic methods described in the present specification or known in the art, and such combinations may be readily carried out by those skilled in the art to which the present invention pertains.
Preparation of an intermediate:
Figure BDA0003069814030000083
wherein Ar is as defined above.
Example 1: and (3) preparing an intermediate 2.
Sequentially adding 40.0mmol of tropinone 1, 60.0mmol of tert-butyl alcohol and 300mL of tetrahydrofuran into a 500mL round-bottom flask, placing the reaction liquid into an ice-water bath, stirring and cooling to 0 ℃, then adding 80mmol of potassium tert-butoxide at one time, keeping the temperature at 0 ℃, continuing stirring for 10min, dissolving 60.0mmol of p-toluenesulfonylmethylisocyanate in 60mL of tetrahydrofuran, slowly dropwise adding the solution into the reaction liquid, continuing stirring the reaction liquid at 0 ℃ for 30min after the dropwise adding is finished, then transferring to room temperature to react for 6h, removing the solvent by rotary evaporation after the reaction is finished, adding 125mL of deionized water, extracting dichloromethane (3X 50 mL), combining organic phases, removing the solvent by decompression to obtain a crude product, separating by column chromatography to obtain 5.4g of colorless oily matter, wherein the yield is 89%; 1 H NMR(400MHz,CDCl 3 )δ3.20–3.18(m,2H),2.73(tt,J＝12.1,5.6Hz,1H),2.28(s,3H),2.09–2.05(m,2H),2.00(dd,J＝12.7,2.1Hz,2H),1.78(ddd,J＝13.4,5.3,3.3Hz,2H),1.53(dd,J＝14.9,6.5Hz,2H). 13 C NMR(101MHz,CDCl 3 )δ122.31,60.07,40.10,34.29,25.62,20.07.MS(GC-MS):C 9 H 14 N 2 [M] + m/z 150.1.
example 2: and (3) preparing an intermediate 3.
Into a 350mL reaction flask, 20.0mmol of Compound 2, 150mL of pyridine, and 30.0mmol of a 20% aqueous solution of ammonium sulfide were sequentially added, and the reaction solution was slowly pouredHeating to 55 ℃ for reaction for 48h, after the reaction is finished, removing the solvent by rotary evaporation, dissolving the reaction residue in 100mL of ice water, adjusting the pH to 8-9 by using saturated sodium carbonate aqueous solution, filtering, and drying a filter cake which can be directly used for the next reaction. 2.1g of light yellow solid, yield 58%; 1 H NMR(400MHz,DMSO-d 6 )δ9.28(s,1H),9.11(s,1H),3.13(br,s,2H),2.85(tt,J＝11.4,5.2Hz,1H),2.21(s,3H),1.99–1.92(m,4H),1.57–1.52(m,2H),1.41–1.36(m,2H)ppm. 13 C NMR(101MHz,DMSO-d 6 )δ212.23,60.73,49.04,42.15,36.23,26.33ppm.HRMS(EI-TOF)calcd for C 9 H 16 N 2 S[M + ]m/z 184.1034,found 184.1035.
example 3: and (4) preparing a target product 4.
And (2) sequentially adding 1mmol of intermediate 3 and 1.1mmol of alpha-bromoarylethanone into a 10mL round-bottom flask, adding 5mL of absolute ethyl alcohol, heating the reaction solution to reflux, reacting for 3h, removing the solvent by rotary evaporation after the reaction is finished, and purifying the crude product by flash chromatography to obtain a target compound 4.
Figure BDA0003069814030000091
Wherein Ar is as defined above.
Example 4: preparation of intermediate 5.
10mmol of compound 3, 15mmol of sodium acetate, 50mL of acetic acid and 13mmol of 40% chloroacetaldehyde aqueous solution are sequentially added into a 100mL round-bottom flask, the mixture is stirred and slowly heated to 80 ℃ for reaction for 12 hours, the solvent is removed under reduced pressure, 30mL of deionized water is added into the reaction residue, the pH is adjusted to 8-9 by saturated sodium carbonate aqueous solution, dichloromethane is used for extraction (3X 30 mL), organic phases are combined, the solvent is removed under reduced pressure to obtain a crude product, and the crude product is subjected to column chromatography to obtain 1.30g of brown oily matter with the yield of 63%. 1 H NMR(400MHz,CDCl 3 )δ7.56(d,J＝3.3Hz,1H),7.14(d,J＝3.3Hz,1H),3.48–3.47(m,2H),3.36(tt,J＝12.0,5.5Hz,1H),2.46(s,3H),2.31–2.24(m,2H),2.18–2.14(m,2H),1.93(ddd,J＝14.5,5.1,3.3Hz,2H),1.79(dd,J＝14.7,6.1Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ173.98,141.92,118.21,61.74,39.05,36.64,32.77,25.62ppm.MS(GC-MS):C 9 H 16 N 2 S[M] + m/z 208.1.
Example 5: and (3) preparing a target product 6.
Adding 2mmol of silver carbonate, 0.05mmol of 1,1' -bis (diphenylphosphino) ferrocene ] palladium dichloride dichloromethane complex, 0.1mmol of triphenylphosphine and 1.2mmol of aryl iodide into a 25mL three-port glass reactor in sequence, then adding 1mmol of compound 5 and 10mL of deionized water, placing the reactor into a microwave synthesizer, inserting an ultrasonic probe, adjusting the height of the probe to be 2-3mm below the liquid level, switching on condensed water, adjusting the microwave power to 60W and the ultrasonic power to 75W, reacting for 1.5 hours, cooling the reaction liquid to room temperature after the raw materials are completely reacted, transferring the reaction liquid to a 125mL separating funnel, extracting dichloromethane (3X 30 mL), filtering the extract liquid by diatomite, combining the extract liquid, removing the solvent by rotary evaporation, and separating by column chromatography to obtain the target compound 6.
Figure BDA0003069814030000092
Wherein Ar is as defined above.
Example 6: and (3) preparing an intermediate 8.
The compound 7 is used as a reaction raw material, and the specific implementation method is the same as the preparation of the intermediate 2. 1 H NMR(400MHz,CDCl 3 )δ4.28–4.23(m,2H),2.98(tt,J＝11.9,5.5Hz,1H),2.08–1.92(m,4H),1.88–1.84(m,2H),1.65–1.59(m,2H),1.48(s,9H)ppm. 13 C NMR(101MHz,CDCl 3 )δ152.98,121.64,79.92,52.67,52.00,34.19,33.51,28.43,27.85,27.16,20.64ppm.
Example 7: preparation of intermediate 9.
Adding 10mmol of intermediate 8, 15mmol of hydroxylamine hydrochloride, 20.0mmol of sodium bicarbonate, 40mL of ethanol and 8mL of deionized water into a 100mL round-bottom flask in sequence, stirring the reaction solution at room temperature for reaction for 1h, heating and refluxing the reaction solution for further reaction for 8h, removing the solvent by rotary evaporation after the reaction is finished, dissolving the reaction residue in 20mL of deionized water, extracting with ethyl acetate (3X 20 mL), combining the extracts, and removing the solvent under reduced pressure to obtain a crude product which can be directly used for the next reaction.
Example 8: preparation of intermediate 10.
2mmol of a compound 9,3mmol of aryl formic acid, 10mmol of triethylamine, 5.0mmol of 1-propylcyclic phosphoric anhydride and 20mL of ethyl acetate are sequentially added into a 50mL round-bottomed flask, the reaction solution is replaced by nitrogen for three times, reflux reaction is carried out for 8 hours under the nitrogen atmosphere, after the reaction is finished, ethyl acetate is removed by rotary evaporation, the reaction residue is dissolved in 20mL of deionized water, the pH is adjusted to 8-9 by saturated aqueous sodium carbonate solution, ethyl acetate is extracted (20 mL multiplied by 3), the extraction solutions are combined, and the crude product is subjected to column chromatography to obtain an intermediate 10.
Example 9: preparation of the target product 11.
Adding 1mmol of compound 10, 10mL of dichloromethane and 2mL of trifluoroacetic acid into a 25mL round-bottom flask in sequence, stirring at room temperature for reaction for 5 hours, removing the solvent by rotary evaporation after the reaction is finished, dissolving the reaction residue in 10mL of deionized water, slowly adjusting the pH to 8-9 by using a saturated sodium carbonate aqueous solution, extracting the dichloromethane (20 mL multiplied by 3), combining the extract solutions, removing the solvent by rotary evaporation, adding 5mmol of a 37% formaldehyde aqueous solution, 10mmol of acetic acid, 5mmol of zinc chips and 10mL of solvent deionized water in sequence, placing the reaction solution in an oil bath at 100 ℃ for reaction for 12 hours, and slowly adding saturated Na after the reaction is finished 2 CO 3 Adjusting pH of the reaction solution to 8-9 with water solution, extracting with dichloromethane (20 mL × 4), mixing extractive solutions, removing solvent by rotary evaporation, and separating by column chromatography to obtain target product 11
Figure BDA0003069814030000101
Wherein Ar is as defined above.
Example 10: preparation of intermediate 13.
Adding 40mmol of demethyltropinone hydrochloride 12, 45mmol of benzyl bromide and 150mL of acetonitrile into a 250mL round-bottom flask in sequence, stirring at room temperature, adding 100mmol of potassium carbonate, heating the reaction solution to reflux, continuing to react for 8 hours, finishing the reaction, cooling the reaction solution to room temperature, performing suction filtration, and using a filter cakeWashed with ethyl acetate (10 mL. Times.3), the filtrate was rotary evaporated to remove the solvent and the crude product was column chromatographed to give 7.5g of intermediate 13 as a colorless oil in 87% yield, 1 H NMR(400MHz,CDCl 3 )δ7.40(d,J＝7.4Hz,2H),7.32(t,J＝7.4Hz,2H),7.24(t,J＝7.3Hz,1H),3.72(s,2H),3.45(br,s,2H),2.66(dd,J＝16.0,4.2Hz,2H),2.19–2.15(m,2H),2.10–2.06(m,2H),1.59(dd,J＝14.7,6.7Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ210.09,139.39,128.44,128.38,127.12,58.59,55.13,48.24,27.86ppm.
example 11: preparation of intermediate 14.
The intermediate 13 is used as a reaction raw material, and the specific implementation steps are the same as the preparation of the intermediate 2. 1 H NMR(400MHz,CDCl 3 )δ7.35–7.29(m,4H),7.26–7.22(m,1H),3.49(s,2H),3.23(br,s,2H),2.91(t,J＝7.7Hz,1H),2.18–2.07(m,6H),1.84–1.81(m,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ128.55,128.28,126.98,124.83,58.47,57.04,33.50,25.52,19.10ppm.
Example 12: preparation of intermediate 15.
And sequentially adding 20mmol of the intermediate 14, 100mL of deionized water and 20mL of concentrated hydrochloric acid into a 250mL round-bottom flask, heating the reaction solution to reflux reaction for 48 hours, cooling the reaction solution to room temperature after the reaction is finished, and removing hydrochloric acid and water under reduced pressure to obtain a brown viscous crude product which can be directly used for the next reaction.
Example 13: preparation of intermediate 16.
And (3) transferring all the obtained intermediate 15 into a 250mL round-bottom flask, adding 4mmol of p-toluenesulfonic acid and 100mL of absolute ethanol, heating to reflux for 8h, after the reaction is finished, cooling the reaction liquid to room temperature, removing the ethanol by rotary evaporation, and separating the crude product by column chromatography to obtain 4.8g of oily matter with the yield of 88%. 1 H NMR(400MHz,CDCl 3 )δ7.39(d,J＝7.6Hz,2H),7.30(t,J＝7.4Hz,2H),7.22(t,J＝7.2Hz,1H),4.11(q,J＝7.1Hz,2H),3.56(s,2H),3.23(br,s,2H),2.61(tt,J＝11.9,5.6Hz,1H),2.05–2.02(m,2H),1.94(t,J＝12.1Hz,2H),1.65–1.56(m,4H),1.23(t,J＝7.1Hz,3H)ppm. 13 C NMR(101MHz,CDCl 3 )δ175.75,139.86,128.53,128.17,126.76,60.25,58.47,56.16,34.85,33.51,26.56,14.28ppm.
Example 14: preparation of intermediate 17.
Adding 30mmol of intermediate 16, 45mmol of 80% hydrazine hydrate and 80mL of anhydrous ethanol into a 250mL round-bottom flask in sequence, heating the reaction solution to a reflux state, stirring for reacting for 48 hours, cooling the reaction solution to room temperature after the reaction is finished, removing the ethanol by rotary evaporation to obtain a white solid crude product, washing the crude product for three times by cold water, filtering to obtain a white solid, and drying the white solid to be directly used for the next reaction. White solid 4.6g,60% yield. 1 H NMR(400MHz,DMSO-d 6 )δ8.88(br,s,1H),7.35(d,J＝7.0Hz,2H),7.31(t,J＝7.4Hz,2H),7.22(t,J＝7.0Hz,1H),4.13(br,s,2H),3.49(s,2H),3.11(br,s,2H),2.44(tt,J＝11.6,5.4Hz,1H),1.98–1.96(m,2H),1.81–1.74(m,2H),1.53(dd,J＝13.6,5.8Hz,2H),1.37–1.32(m,2H)ppm. 13 C NMR(101MHz,DMSO-d 6 )δ174.07,140.08,128.24,128.03,126.51,58.19,55.51,33.71,33.44,26.16ppm.
Example 15: preparation of intermediate 18.
Adding 2mmol of compound 17,3mmol of aryl formic acid, 5mmol of triethylamine, 5mmol of 1-propyl cyclic phosphoric anhydride and 20mL of ethyl acetate into a 50mL round bottom flask in sequence, replacing reaction liquid with nitrogen for three times, carrying out reflux reaction for 8 hours under the nitrogen atmosphere, cooling to room temperature after the reaction is finished, removing the ethyl acetate by rotary evaporation, dissolving reaction residues in 20mL deionized water, adjusting the pH to 8-9 by using saturated sodium carbonate aqueous solution, extracting with ethyl acetate (20 mL multiplied by 3), combining extract liquor, removing the solvent by rotary evaporation of the extract liquor, and carrying out column chromatography separation to obtain the target product.
Example 16: preparation of intermediate 19.
Adding 18 mmol of compound, 10mL of anhydrous acetonitrile and 2mL of phosphorus oxychloride into a 25mL round-bottom flask in sequence, heating the reaction solution to a reflux state, stirring for reaction for 12h, cooling to room temperature after the reaction is finished, slowly adding 5mL of deionized water, continuing stirring for 10min, slowly dropwise adding a saturated sodium carbonate aqueous solution into the reaction solution to adjust the pH of the reaction solution to 8-9, carrying out rotary evaporation to remove the acetonitrile, dissolving the reaction residue in 10mL of deionized water, extracting with dichloromethane (3X 20 mL), combining the extracts, removing the solvent from the extracts through rotary evaporation, and carrying out column chromatographic separation to obtain the target product.
Example 17: preparation of target compound 20.
Adding 0.5mmol of intermediate 19, 10mL of anhydrous methanol, 100.0mg of 10% palladium-carbon and 5.0mmol of ammonium formate into a 25mL round-bottom flask in sequence, stirring and reacting overnight at room temperature, after the reaction is finished, carrying out suction filtration on reaction liquid through diatomite, removing a solvent from filtrate through rotary evaporation, dissolving the filtrate in 10mL of deionized water, extracting with dichloromethane (10 mL multiplied by 3), combining extract liquor and removing the solvent, adding 2.5mmol of zinc chips, 2.5mmol of 37% formaldehyde aqueous solution, 5mmol of acetic acid and 10mL of deionized water in sequence, placing the reaction liquid at 100 ℃ for reaction for 12 hours, after the reaction is finished, cooling the reaction liquid to room temperature, adjusting the pH of the reaction liquid to 8-9 with saturated sodium carbonate solution, extracting the reaction liquid with dichloromethane (20 mL multiplied by 3), combining extract liquor, removing the solvent under reduced pressure, and carrying out column chromatography to obtain the target compound 20.
Example 18: preparation of intermediate 21.
2mmol of intermediate 18, 20mL of anhydrous methanol, 400.0mg of 10% palladium carbon and 5mmol of ammonium formate are sequentially added into a 50mL round-bottom flask, the mixture is stirred and reacted overnight at room temperature, after the reaction is finished, the reaction solution is filtered by suction through diatomite, the filtrate is dissolved in 20mL of deionized water after the solvent is removed by rotary evaporation, and is extracted by dichloromethane (20 mL multiplied by 3), after the extracts are combined and the solvent is removed, the crude product can be directly used for the next reaction without column chromatography separation.
Example 19: preparation of intermediate 22.
Adding 1.5mmol of intermediate 21, 20mL of toluene and 4mmol of Lawson reagent into a 50mL round-bottom flask in sequence, heating the reaction solution to a reflux state for reaction for 12 hours, cooling the reaction solution to room temperature after the raw materials are completely reacted, adding 20mL of deionized water, extracting with ethyl acetate (20 mL multiplied by 3), combining the extracts, removing the solvent, and separating the crude product by column chromatography for the next reaction.
Example 20: preparation of target compound 23.
Adding 0.5mmol of intermediate 22,2.5mmol of zinc chips, 2.5mmol of 37% formaldehyde aqueous solution, 5mmol of acetic acid and 10mL of deionized water into a 25mL round-bottom flask in sequence, placing the reaction solution at 100 ℃ for reacting for 12 hours, after the reaction is finished, cooling the reaction solution to room temperature, adjusting the pH of the reaction solution to 8-9 by using a saturated sodium carbonate solution, extracting the reaction solution by dichloromethane (20 mL multiplied by 3), combining the extraction solutions, removing the solvent under reduced pressure, and separating by column chromatography to obtain the target compound.
Figure BDA0003069814030000121
Wherein R is as defined above.
Example 21: preparation of intermediate 25.
Adding 150mL of dichloromethane and 40mmol of compound 24 into a 250mL round-bottom flask in turn, then adding 60mmol of imidazole and 52mmol of triphenylphosphine in turn, stirring and cooling to 0 ℃, then adding 48mmol of iodine elementary substance in one time, continuing stirring at 0 ℃ for reaction for 30min, then turning to room temperature for reaction overnight, after the reaction is finished, removing insoluble substances by suction filtration, washing a filter cake with dichloromethane (20 mL multiplied by 3), combining filtrates, removing a solvent under reduced pressure, adding 30mL of deionized water into a reaction residue, adding a saturated sodium carbonate aqueous solution to adjust the pH to 8-9, extracting with dichloromethane (50 mL multiplied by 3), removing the solvent from an extract under reduced pressure, and separating a crude product by column chromatography to obtain a target product.
Figure BDA0003069814030000122
Wherein Ar is as defined above.
Example 22: preparation of intermediate 27.
5mmol of the compound 26,7.5mmol of N, N-dimethylformamide dimethyl acetal and 20mL of anhydrous ethanol are sequentially added into a 100mL round bottom flask, the mixture is heated to reflux for reaction for 48 hours, after the reaction is finished, the reaction liquid is cooled to room temperature, the ethanol is removed under reduced pressure, the reaction residue is dissolved in 50mL of ethyl acetate and washed by saturated saline (20 mL multiplied by 3), the solvent is removed from the organic phase under reduced pressure, and the obtained crude product can be directly used for the next reaction.
Example 23: preparation of intermediate 28.
Adding 3mmol of intermediate 27,4.5mmol of hydrazine hydrochloride, 0.6mmol of p-toluenesulfonic acid and 20mL of absolute ethyl alcohol into a 50mL round-bottom flask in sequence, heating to reflux and reacting for 6-8h, cooling reaction liquid to room temperature after reaction, removing the ethyl alcohol under reduced pressure, dissolving reaction residues in 30mL of deionized water, extracting with ethyl acetate (30 mL multiplied by 3), combining extracts, and separating crude products through column chromatography to obtain the target product.
Example 24: preparation of intermediate 29.
Adding 2mmol of intermediate 28, 10mL of anhydrous N, N-dimethylformamide and 5mmol of sodium hydride into a 25mL round-bottom flask in sequence, reacting the reaction solution at room temperature for 10min under the nitrogen atmosphere, then adding 3mmol of intermediate 25, slowly heating the reaction solution to 70 ℃, continuing to react for 12h, after the reaction is finished, cooling the reaction solution to room temperature, slowly dropwise adding 1.0mL of deionized water to quench the residual sodium hydride, transferring the reaction solution to a separating funnel, adding deionized water (20 mL), extracting with ethyl acetate (20 mL multiplied by 3), combining the extraction solutions, removing the solvent by rotary evaporation, and then carrying out column chromatography separation to obtain the target product.
Example 25: preparation of target compound 30.
Taking the intermediate 29 as a reaction raw material, and when the R group is benzyl or benzyloxycarbonyl, carrying out the specific steps of the preparation method of the target product 20; when the R group is tert-butyloxycarbonyl, the specific implementation steps are the same as the preparation method of the target product 11.
Figure BDA0003069814030000131
Wherein R and Ar are as defined above.
Example 26: preparation of intermediate 32.
Obtained by reacting 4-bromo-1-H-pyrazole 31 with the intermediate 25 under alkaline conditions, and the specific implementation method is the same as the preparation method of the intermediate 29.
Example 27: preparation of intermediate 33.
Adding 2mmol of intermediate 32,3mmol of arylboronic acid, 4mmol of potassium carbonate and 0.1mmol of tetrakistriphenylphosphine palladium into a 25mL round-bottom flask in sequence, then adding 10mL of methylbenzene, 1mL of absolute ethyl alcohol and 1mL of deionized water, placing the reaction solution at 90 ℃ for reflux reaction for 16h, after the reaction is finished, cooling the reaction solution to room temperature, removing the solvent under reduced pressure, dissolving the reaction residue in 20mL of deionized water, extracting with ethyl acetate (20 mL multiplied by 3), combining the extracts, and separating the crude product by column chromatography to obtain the target product.
Example 28: preparation of target compound 34.
The intermediate 33 is a reaction raw material, and when the R group is tert-butyloxycarbonyl, the specific implementation steps are the same as the preparation method of the target product 11.
Figure BDA0003069814030000132
Figure BDA0003069814030000141
In the formula, R and R 1 The definition is the same as above.
Example 29: preparation of intermediate 36.
Adding 20mmol of N-methyl-5-hydroxypyrazole 35 and 6.0mL of anhydrous N, N-dimethylformamide into a 25mL round-bottom flask in sequence, placing the reaction solution in an ice-water bath, stirring and cooling to 0 ℃, then slowly adding 6.0mL of phosphorus tribromide into the reaction solution dropwise, keeping the temperature at 0 ℃ after dropwise adding, continuing to react for 10min, then slowly raising the reaction temperature to 80 ℃ and continuing to react for 8h, after the reaction is finished, cooling the reaction solution to room temperature, slowly adding 20mL of deionized water into the reaction solution until the viscous reaction solution is completely dissolved, slowly adjusting the pH to 8-9 by using a saturated sodium carbonate aqueous solution, extracting the reaction solution by using ethyl acetate (30 mL multiplied by 3), washing an extraction solution (20 mL multiplied by 3) by using saturated saline, removing the solvent by rotary evaporation of the extraction solution, and separating a crude product by using column chromatography to obtain a target product. 1 H NMR(400MHz,CDCl 3 )δ9.77(s,1H),7.97(s,1H),3.93(s,3H)ppm.
Example 30: preparation of intermediate 41.
10.0mmol of 1-methyl-1H-pyrazole-5-formaldehyde and 20mL of reaction solvent N, N-bis are sequentially added into a 100mL round-bottom flaskAnd (2) stirring the mixture at room temperature until the raw materials are dissolved, then dissolving 11mmol of N-bromosuccinimide in 10mL of N, N-dimethylformamide, slowly dropwise adding the solution into the reaction solution, placing the reaction solution at room temperature, continuously stirring for reacting for 18 hours, adding 10mL of 20% sodium hydroxide aqueous solution after the reaction is finished, continuously stirring for 10 minutes, then adding 50mL of deionized water into the reaction solution, extracting with ethyl acetate (30 mL multiplied by 3), combining the extracts, washing with saturated salt water (20 mL multiplied by 3), removing the solvent from the extracts through rotary evaporation, and separating the crude product through column chromatography to obtain the target product. 1 H NMR(400MHz,CDCl 3 )δ9.87(s,1H),7.50(s,1H),4.14(s,3H)ppm.
Example 31: preparation of intermediate 37 and intermediate 42.
The intermediate 36 or the intermediate 41 is used as a reaction raw material, and the specific implementation steps are the same as the synthesis method of the intermediate 33.
Example 32: preparation of intermediate 38 and intermediate 43.
And sequentially adding 0.5mmol of intermediate 37 or 42,1.1mmol of p-toluenesulfonylhydrazide and 6mL of n-butyl alcohol into a 20mL microwave reaction tube provided with a magnetic stirrer, sealing the microwave reaction tube, placing the microwave reaction tube in a microwave synthesizer at 120 ℃ for reaction for 5min, removing the solvent under reduced pressure after the reaction is finished, and separating by column chromatography to obtain an intermediate 38 or an intermediate 43.
Example 33: preparation of intermediate 39 and intermediate 44.
Adding 1mmol of intermediate 38 or intermediate 43 into a 20mL microwave reaction tube equipped with a magnetic stirrer in sequence, then quickly adding 15.0g of pyridine hydrochloride, quickly covering the microwave tube, placing the microwave tube into a microwave synthesizer, keeping the temperature of 200 ℃ for reaction for 5 hours, dissolving the reactant into 30mL deionized water after the reaction is finished, extracting with ethyl acetate (20 mL multiplied by 4), combining the extracts, removing the solvent by rotary evaporation, and separating by column chromatography to obtain intermediate 39 or intermediate 44.
Example 34: preparation of intermediate 45 and intermediate 47.
The intermediate 39 and the intermediate 25 react under alkaline conditions to obtain an intermediate 45 and an intermediate 47, and the preparation method of the intermediate 29 is specifically implemented.
Example 35: preparation of intermediate 49 and intermediate 51.
The intermediate 44 and the intermediate 25 react under alkaline conditions to obtain an intermediate 49 and an intermediate 51, and the specific implementation steps are the same as those of the preparation method of the intermediate 29.
Example 36: preparation of the target products 46, 48, 50, 52.
Respectively taking intermediates 45, 47, 49 and 51 as raw materials to react. When the R group is tert-butyloxycarbonyl, the specific procedure is the same as the above-mentioned preparation of intermediate 11.
The following compounds were prepared according to the methods described in examples 1 to 36 above using different starting materials, NMR spectra: (NMR) 1 H NMR) carbon spectrum (C) 13 C NMR), high Resolution Mass Spectrometry (HRMS) characterization data as follows:
Figure BDA0003069814030000151
1 H NMR(400MHz,CD 3 OD)δ7.91(d,J＝7.1Hz,2H),7.67(s,1H),7.41(t,J＝7.5Hz,2H),7.36–7.26(m,1H),3.69(s,2H),3.59–3.51(m,1H),2.59(s,3H),2.24(t,J＝12.1Hz,4H),2.17–2.05(m,2H),1.97(d,J＝8.6Hz,2H). 13 C NMR(101MHz,CD 3 OD)δ174.75,156.15,135.85,129.90,129.26,127.47,113.90,64.00,39.82,37.96,33.43,25.94.HRMS(EI-TOF)calcd for C 17 H 20 N 2 S[M + ]m/z 284.1347；found,284.1346.
Figure BDA0003069814030000152
1 H NMR(400MHz,CD 3 OD)δ7.85(d,J＝7.8Hz,2H),7.47(s,1H),7.29(d,J＝7.9Hz,2H),3.71(s,2H),3.57–3.48(m,1H),2.57(s,3H),2.31(s,3H),2.22–2.03(m,6H),1.94(d,J＝8.7Hz,2H). 13 C NMR(101MHz,CD 3 OD)δ173.91,157.23,134.91,131.30,129.46,127.59,114.20,63.80,38.77,38.71,34.50,25.92,21.38.HRMS(EI-TOF)calcd for C 18 H 22 N 2 S[M + ]m/z 298.1504；found,298.1502.
Figure BDA0003069814030000153
1 H NMR(400MHz,CD 3 OD)δ7.71(d,J＝8.8Hz,2H),7.39(s,1H),6.85(d,J＝8.8Hz,2H),3.71(s,3H),3.58–3.38(m,3H),2.45(s,3H),2.23–1.97(m,6H),1.87(d,J＝8.5Hz,2H). 13 C NMR(101MHz,CD 3 OD)δ175.06,161.20,156.16,128.71,115.11,111.74,63.71,55.81,39.85,38.30,33.62,26.06.HRMS(EI-TOF)calcd for C 18 H 22 N 2 OS[M + ]m/z 314.1453；found,314.1455.
Figure BDA0003069814030000161
1 H NMR(400MHz,CD 3 OD)δ7.96–7.88(m,2H),7.63(s,1H),7.13(t,J＝8.7Hz,2H),3.67(s,2H),3.62–3.52(m,1H),2.58(s,3H),2.33–2.08(m,6H),1.99(d,J＝8.1Hz,2H). 13 C NMR(101MHz,CD 3 OD)δ175.05,164.06(d,J＝246.0Hz),155.15,132.35,129.34(d,J＝8.2Hz),116.50(d,J＝21.9Hz),113.48,63.85,39.81,38.09,33.52,25.99.HRMS(EI-TOF)calcd for C 17 H 19 FN 2 S[M + ]m/z 302.1253；found,302.1252.
Figure BDA0003069814030000162
1 H NMR(400MHz,CD 3 OD)δ7.89(d,J＝8.6Hz,2H),7.71(s,1H),7.39(d,J＝8.6Hz,2H),3.78(s,2H),3.67–3.55(m,1H),2.66(s,3H),2.37–2.14(m,6H),2.05(d,J＝8.1Hz,2H). 13 C NMR(101MHz,CD 3 OD)δ174.66,154.95,134.83,134.55,129.90,128.88,114.39,64.18,39.67,37.85,33.29,25.80.HRMS(EI-TOF)calcd for C 17 H 19 35 ClN 2 S[M + ]m/z 318.0957；found,318.0959；calcd for C 17 H 19 37 ClN 2 S[M + ]m/z 320.0928；found,320.0927.
Figure BDA0003069814030000163
1 H NMR(400MHz,CD 3 OD)δ7.82(d,J＝8.6Hz,2H),7.72(s,1H),7.54(d,J＝8.6Hz,2H),3.73(s,2H),3.67–3.51(m,1H),2.62(s,3H),2.36–2.11(m,6H),2.02(d,J＝8.7Hz,2H). 13 C NMR(101MHz,CD 3 OD)δ174.94,154.95,134.95,132.91,129.15,122.90,114.45,64.00,39.76,37.99,33.42,25.91.HRMS(EI-TOF)calcd for C 17 H 19 79 BrN 2 S[M + ]m/z 362.0452；found,362.0449；calcd for C 17 H 19 81 BrN 2 S[M + ]m/z 364.0432；found,364.0428.
Figure BDA0003069814030000164
1 H NMR(400MHz,CD 3 OD)δ8.27(d,J＝9.0Hz,2H),8.10(d,J＝9.0Hz,2H),7.84(s,1H),3.80(s,2H),3.70–3.55(m,1H),2.68(s,3H),2.43–2.35(m,4H),2.22(d,J＝16.6Hz,2H),2.08(d,J＝8.8Hz,2H). 13 C NMR(101MHz,CD 3 OD)δ175.21,153.91,148.52,141.73,128.27,125.39,117.71,64.02,40.21,37.90,33.68,26.31.HRMS(EI-TOF)calcd for C 17 H 19 N 3 O 2 S[M + ]m/z 329.1198；found,329.1197.
Figure BDA0003069814030000165
1 H NMR(400MHz,CD 3 OD)δ8.11(d,J＝8.2Hz,2H),7.92(s,1H),7.69(d,J＝8.4Hz,2H),3.91(s,2H),3.71–3.63(m,1H),2.76(s,3H),2.44–2.35(m,4H),2.23(d,J＝10.1,2H),2.12(d,J＝8.8Hz,2H). 13 C NMR(101MHz,CD 3 OD)δ174.38,154.42,139.32,130.62(q,J＝32.3Hz),127.86,126.76(q,J＝3.8Hz),125.78(q,J＝271.3Hz),116.45,64.52,39.66,37.49,33.09,25.68.HRMS(EI-TOF)calcd for C 18 H 19 F 3 N 2 S[M + ]m/z 352.1221；found,352.1224.
Figure BDA0003069814030000171
1 H NMR(400MHz,CD 3 OD)δ7.94(s,1H),7.73–7.54(m,2H),7.39(d,J＝8.4Hz,1H),3.71(s,2H),3.54–3.47(m,1H),2.58(s,3H),2.34–2.06(m,6H),1.98(d,J＝8.5Hz,2H). 13 C NMR(101MHz,CD 3 OD)δ174.64,153.74,135.93,133.93,132.89,131.94,129.37,126.83,115.43,64.18,39.83,37.78,33.37,25.97.HRMS(EI-TOF)calcd for C 17 H 18 35 Cl 2 N 2 S[M + ]m/z 352.0568；found,352.0562；calcd for C 17 H 18 35 Cl 37 ClN 2 S[M + ]m/z 354.0538；found,354.0543；calcd for C 17 H 18 37 Cl 2 N 2 S[M + ]m/z 356.0509；found,356.0518.
Figure BDA0003069814030000172
1 H NMR(400MHz,CD 3 OD)δ7.78–7.74(m,3H),7.23(t,J＝1.9Hz,1H),3.74(s,2H),3.58–3.48(m,1H),2.60(s,3H),2.27–2.16(m,4H),2.14–2.07(m,2H),1.99(d,J＝8.8Hz,2H). 13 C NMR(101MHz,CD 3 OD)δ174.77,153.05,138.85,136.53,128.53,125.73,116.48,64.30,39.64,37.73,33.19,25.72.HRMS(EI-TOF)calcd for C 17 H 18 35 Cl 2 N 2 S[M + ]m/z 352.0568；found,352.0563；calcd for C 17 H 18 35 Cl 37 ClN 2 S[M + ]m/z 354.0538；found,354.0542；calcd for C 17 H 18 37 Cl 2 N 2 S[M + ]m/z 356.0509；found,356.0523.
Figure BDA0003069814030000173
1 H NMR(400MHz,CD 3 OD)δ7.60(s,1H),7.52(s,1H),6.63(d,J＝3.0Hz,1H),6.40(d,J＝3.3Hz,1H),3.71(s,2H),3.57–3.48(m,1H),2.55(s,3H),2.30–2.14(m,6H),2.07(d,J＝9.2Hz,2H). 13 C NMR(101MHz,CD 3 OD)δ172.35,149.26,142.01,140.04,114.35,110.86,105.92,64.30,39.13,37.54,33.24,25.74.HRMS(EI-TOF)calcd for C 15 H 18 N 2 OS[M + ]m/z 274.1140；found,274.1141.
Figure BDA0003069814030000174
1 H NMR(400MHz,CD 3 OD)δ8.68(d,J＝6.3Hz,2H),7.89(d,J＝6.3Hz,2H),7.73(s,1H),3.72(s,2H),3.67–3.50(m,1H),2.62(s,3H),2.30–2.17(m,4H),2.13–2.06(m,2H),1.98(d,J＝8.4Hz,2H). 13 C NMR(101MHz,CD 3 OD)δ174.83,151.21,146.35,142.18,122.62,116.27,64.86,39.57,37.31,32.89,26.20.HRMS(EI-TOF)calcd for C 16 H 19 N 3 S[M + ]m/z 285.1300；found,285.1299.
Figure BDA0003069814030000175
1 H NMR(400MHz,CD 3 OD)δ7.73(s,1H),7.45(d,J＝8.7Hz,2H),6.92(d,J＝8.8Hz,2H),3.78(s,3H),3.36–3.27(m,3H),2.30(s,3H),2.14–2.11(m,2H),2.00–1.93(m,2H),1.89(ddd,J＝13.3,5.3,2.9Hz,2H),1.73(dd,J＝14.1,6.0Hz,2H)ppm. 13 C NMR(101MHz,CD 3 OD)δ175.40,161.35,139.81,137.08,128.91,125.04,115.68,62.48,55.92,40.26,38.74,34.48,26.81ppm.HRMS(EI-TOF)calcd for C 18 H 22 N 2 OS[M + ]m/z 314.1453,found 314.1457.
Figure BDA0003069814030000181
1 H NMR(400MHz,CD 3 OD)δ7.58(s,1H),7.32(d,J＝7.4Hz,1H),7.28–7.27(m,2H),7.25–7.20(m,1H),3.50–3.45(m,3H),2.43(s,3H),2.35(s,3H),2.22–2.19(m,2H),2.12–2.00(m,4H),1.86(dd,J＝14.3,5.8Hz,2H)ppm. 13 C NMR(101MHz,CD 3 OD)δ176.40,140.99,138.28,137.46,132.01,131.61,129.87,127.36,62.97,40.10,38.49,34.10,26.52,21.28ppm.HRMS(EI-TOF)calcd for C 18 H 22 N 2 S[M + ]m/z 298.1504,found 298.1505.
Figure BDA0003069814030000182
1 H NMR(400MHz,CD 3 OD)δ7.74(s,1H),7.42(d,J＝7.3Hz,2H),7.25(t,J＝7.5Hz,2H),7.18(t,J＝7.3Hz,1H),3.27–3.18(m,3H),2.20(s,3H),2.02–1.99(m,2H),1.91–1.85(m,2H),1.80(ddd,J＝13.3,5.1,2.8Hz,2H),1.63(dd,J＝14.2,6.1Hz,2H)ppm. 13 C NMR(101MHz,CD 3 OD)δ176.21,139.85,138.31,132.58,130.34,129.46,127.60,62.60,40.25,38.66,34.46,26.74ppm.HRMS(EI-TOF)calcd for C 17 H 20 N 2 S[M + ]m/z 284.1347,found 284.1348.
Figure BDA0003069814030000183
1 H NMR(400MHz,CD 3 OD)δ7.87(s,1H),7.53–7.50(m,2H),7.38–7.34(m,2H),3.29–3.28(m,3H),2.32(s,3H),2.15–2.13(m,2H),2.02–1.90(m,4H),1.75(dd,J＝14.3,5.9Hz,2H)ppm. 13 C NMR(101MHz,CD 3 OD)δ176.93,138.83,138.46,135.07,131.33,130.38,128.96,62.45,40.32,38.77,34.61,26.82ppm.HRMS(EI-TOF)calcd for C 17 H 19 35 ClN 2 S[M + ]m/z 318.0957,found 318.0956.calcd for C 17 H 19 37 ClN 2 S[M + ]m/z 320..0928,found 320..0928.
Figure BDA0003069814030000184
1 H NMR(400MHz,CDCl 3 )δ7.78(s,1H),7.63(s,1H),7.41–7.38(m,2H),7.21(t,J＝7.9Hz,1H),3.40–3.34(m,3H),2.39(s,3H),2.14–2.09(m,4H),1.96–1.93(m,2H),1.74(dd,J＝13.8,5.4Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ175.44,138.02,136.36,133.51,130.72,130.38,129.16,125.06,122.92,61.06,39.70,37.53,33.81,26.02ppm.HRMS(EI-TOF)calcd for C 17 H 19 79 BrN 2 S[M + ]m/z 362.0452,found 362.0454.calcd for C 17 H 19 81 BrN 2 S[M + ]m/z 364.0432,found 364.0436.
Figure BDA0003069814030000191
1 H NMR(400MHz,CDCl 3 )δ8.18–8.15(m,2H),7.89(s,1H),7.62–7.58(m,2H),3.50(br,s,2H),3.39(tt,J＝11.9,5.4Hz,1H),2.48(s,3H),2.35(t,J＝12.4Hz,2H),2.20–2.17(m,2H),2.00–1.97(m,2H),1.82(dd,J＝14.9,6.1Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ175.07,146.05,138.80,136.88,135.20,125.93,123.46,60.79,38.37,35.88,32.55,24.68ppm.HRMS(EI-TOF)calcd for C 17 H 19 N 3 O 2 S[M + ]m/z 329.1198,found 329.1197.
Figure BDA0003069814030000192
1 H NMR(400MHz,CDCl 3 )δ7.78(s,1H),7.51(br,s,4H),3.50(br,s,2H),3.35(tt,J＝11.9,5.4Hz,1H),2.47(s,3H),2.33(t,J＝12.2Hz,2H),2.18–2.14(m,2H),1.98–1.92(m,2H),1.79(dd,J＝14.6,6.0Hz,2H)ppm. 13 C NMR(100MHz,CDCl 3 )δ173.71,137.72,135.95,133.97,128.75(q,J＝32.7Hz),125.70,124.98(q,J＝3.7Hz),122.97(q,J＝272.1Hz),60.86,38.30,35.76,32.37,24.65ppm.HRMS(EI-TOF)calcd for C 18 H 19 F 3 N 2 S[M + ]m/z 352.1221,found 352.1222.
Figure BDA0003069814030000193
1 H NMR(400MHz,CD 3 OD)δ7.65(s,1H),7.42–7.38(m,2H),7.03–6.97(m,2H),3.50(br,s,2H),3.35(tt,J＝11.6,5.3Hz,1H),2.48(s,3H),2.33(t,J＝12.3Hz,2H),2.19–2.14(m,2H),1.98–1.94(m,2H),1.82(dd,J＝14.4,6.1Hz,2H)ppm. 13 C NMR(101MHz,CD 3 OD)δ172.24(s),161.76(d,J＝248.4Hz),136.94,136.16,127.49(d,J＝8.2Hz),126.43(d,J＝3.4Hz),115.15(d,J＝22.0Hz),61.15,37.92,35.51,31.80,24.40ppm.HRMS(EI-TOF)calcd for C 17 H 19 FN 2 S[M + ]m/z 302.1253,found 302.1252.
Figure BDA0003069814030000194
1 H NMR(400MHz,CD 3 OD)δ8.28(s,1H),8.09(dd,J＝8.2,2.0Hz,1H),7.85(s,1H),7.76(d,J＝7.8Hz,1H),7.51(t,J＝8.0Hz,1H),3.68(br,s,2H),3.44(tt,J＝12.0,5.5Hz,1H),2.61(s,3H),2.61–2.54(m,2H),2.28–2.25(m,2H),2.07–2.02(m,2H),1.93(dd,J＝14.6,5.8Hz,2H)ppm. 13 C NMR(100MHz,CD 3 OD)δ175.00,150.05,140.35,137.96,134.20,133.79,131.76,124.16,122.36,64.27,39.81,37.31,33.57,26.07ppm.HRMS(EI-TOF)calcd for C 17 H 19 N 3 O 2 S[M + ]m/z 329.1198,found 329.1197.
Figure BDA0003069814030000195
1 H NMR(400MHz,CD 3 OD)δ7.75(s,1H),7.43–7.37(m,2H),7.26–7.22(m,2H),3.79(br,s,2H),3.48(tt,J＝12.0,5.5Hz,1H),2.66(s,3H),2.44–2.37(m,2H),2.32–2.28(m,2H),2.15–2.10(m,2H),2.01(dd,J＝14.8,5.8Hz,2H)ppm. 13 C NMR(101MHz,CD 3 OD)δ174.63,142.50,136.26,133.82,132.76,131.86,131.16,130.98,128.65,64.21,39.78,37.11,33.34,26.21ppm.HRMS(EI-TOF)calcd for C 17 H 19 35 ClN 2 S[M + ]m/z 318.0957,found 318.0956.calcd for C 17 H 19 37 ClN 2 S[M + ]m/z 320.0928,found 320.0930.
Figure BDA0003069814030000201
1 H NMR(400MHz,CDCl 3 )δ7.87(d,J＝1.3Hz,1H),7.32(t,J＝8.1Hz,1H),7.28–7.22(m,2H),3.35–3.28(m,3H),2.32(s,3H),2.09–2.01(m,4H),1.91–1.86(m,2H),1.68(dd,J＝14.4,6.2Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ175.08,157.49(d,J＝254.7Hz),139.57(d,J＝7.4Hz),129.03(d,J＝4.5Hz),128.90(d,J＝4.0Hz),126.93(d,J＝3.5Hz),120.52(d,J＝9.6Hz),118.89(d,J＝25.5Hz),117.87(d,J＝13.8Hz),60.13,38.77,36.67,32.80,25.10ppm.HRMS(EI-TOF)calcd for C 17 H 18 79 BrFN 2 S[M + ]m/z 380.0358,found 380.0359.calcd for C 17 H 18 81 BrFN 2 S[M + ]m/z 382.0338,found 382.0338.
Figure BDA0003069814030000202
1 H NMR(400MHz,CDCl 3 )δ7.75(s,1H),7.40(d,J＝8.1Hz,2H),7.18(d,J＝7.9Hz,2H),3.40–3.32(m,3H),2.39(s,3H),2.36(s,3H),2.15–2.08(m,4H),1.95(ddd,J＝13.5,5.2,3.3Hz,2H),1.75(dd,J＝14.4,6.2Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ174.34,138.35,137.96,136.85,129.65,128.75,126.50,61.20,39.75,37.70,33.87,26.13,21.18ppm.HRMS(EI-TOF)calcd for C 18 H 22 N 2 S[M + ]m/z 298.1504,found 298.1505.
Figure BDA0003069814030000203
1 H NMR(400MHz,CDCl 3 )δ7.69(s,1H),7.06(s,2H),6.87(s,1H),3.33–3.25(m,3H),2.31(s,3H),2.26(s,3H),2.08–1.98(m,4H),1.87(ddd,J＝13.0,4.6,2.6Hz,2H),1.67(dd,J＝14.4,6.3Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ173.59,137.56,137.44,136.12,130.37,128.73,123.47,60.06,38.67,36.65,32.87,25.15,20.23ppm.HRMS(EI-TOF)calcd for C 19 H 24 N 2 S[M + ]m/z 312.1660,found 312.1663.
Figure BDA0003069814030000204
1 H NMR(400MHz,CDCl 3 )δ7.72(s,1H),7.45–7.42(m,2H),7.33–7.30(m,2H),3.73(br,s,2H),3.42(tt,J＝10.0,5.4Hz,1H),2.68–2.62(m,5H),2.30–2.27(m,2H),2.07–2.02(m,2H),1.96(dd,J＝14.8,5.9Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ174.29,136.71,136.03,131.11,129.56,127.01,120.89,60.17,38.76,36.69,32.91,25.08ppm.HRMS(EI-TOF)calcd for C 17 H 19 79 BrN 2 S[M + ]m/z 362.0452,found 362.0451.calcd for C 17 H 19 81 BrN 2 S[M + ]m/z 364.0432,found 364.0434.
Figure BDA0003069814030000211
1 H NMR(400MHz,CDCl 3 )δ7.83(s,1H),7.59(d,J＝8.4Hz,2H),7.53(d,J＝8.4Hz,2H),3.36–3.30(m,3H),2.33(s,3H),2.10–2.04(m,4H),1.92–1.87(m,2H),1.69(dd,J＝14.0,5.8Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ175.89,138.28,135.18,135.08,131.79,125.81,117.51,110.23,60.20,38.92,36.81,33.02,25.04ppm.HRMS(EI-TOF)calcd for C 18 H 19 N 3 S[M + ]m/z 309.1300,found 309.1299.
Figure BDA0003069814030000212
1 H NMR(400MHz,CDCl 3 )δ7.77(s,1H),7.54–7.51(m,2H),7.23(d,J＝8.1Hz,2H),3.40–3.33(m,1H),3.31–3.29(m,2H),2.36(s,3H),2.14–2.11(m,2H),2.05(td,J＝13.1,2.3Hz,2H),1.94(ddd,J＝13.3,5.1,3.0Hz,2H),1.72(dd,J＝14.4,6.3Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ175.82,148.72,137.83,136.52,130.43,127.87,121.45,120.38(q,J＝257.6Hz).61.04,39.94,37.98,34.02,26.13ppm.HRMS(EI-TOF)calcd for C 18 H 19 F 3 N 2 OS[M + ]m/z 368.1170,found 368.1173.
Figure BDA0003069814030000213
1 H NMR(400MHz,CDCl 3 )δ7.71(s,1H),7.26–7.22(m,2H),7.18(t,J＝7.4Hz,1H),7.04(d,J＝7.1Hz,1H),3.54(br,s,2H),3.37(tt,J＝11.4,5.0Hz,1H),2.53(s,3H),2.40(t,J＝12.8Hz,2H),2.30(s,3H),2.21–2.18(m,2H),1.99–1.96(m,2H),1.87–1.82(m,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ171.73,137.99,137.74,136.25,130.25,127.96,127.90,126.39,122.77,60.90,37.87,35.35,32.15,24.63,20.35ppm.HRMS(EI-TOF)calcd for C 18 H 22 N 2 S[M + ]m/z 298.1504,found 298.1503.
Figure BDA0003069814030000214
1 H NMR(400MHz,CDCl 3 )δ7.72(s,1H),7.21(t,J＝7.9Hz,1H),7.03(d,J＝7.5Hz,1H),6.97(s,1H),6.78(d,J＝8.2Hz,1H),3.76(s,3H),3.50(br,s,2H),3.35(tt,J＝11.5,5.3Hz,1H),2.49(s,3H),2.33(t,J＝12.6Hz,2H),2.19–2.16(m,2H),1.98–1.95(m,2H),1.84–1.79(m,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ172.29,158.94,137.54,136.56,131.65,129.05,118.19,112.61,111.29,60.67,54.34,37.94,35.52,32.26,24.72ppm.HRMS(EI-TOF)calcd for C 18 H 22 N 2 OS[M + ]m/z 314.1453,found 314.1456.
Figure BDA0003069814030000221
1 H NMR(400MHz,CDCl 3 )δ7.75(s,1H),7.33(s,1H),7.32(s,1H),7.22(t,J＝1.8Hz,1H),3.49(br,s,2H),3.41–3.32(m,1H),2.48(s,3H),2.34(t,J＝12.8Hz,2H),2.20–2.17(m,2H),1.99–1.94(m,2H),1.82(dd,J＝14.3,5.8Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ176.11,138.80,135.55,135.43,134.44,127.77,124.83,61.27,39.72,37.51,33.91,26.03ppm.HRMS(EI-TOF)calcd for C 17 H 18 35 Cl 2 N 2 S[M + ]m/z 352.0568,found 352.0567.calcd for C 17 H 18 35 Cl 37 ClN 2 S[M + ]m/z 354.0538,found 354.0544.calcd for C 17 H 18 37 Cl 2 N 2 S[M + ]m/z 356.0509,found 356.0518.
Figure BDA0003069814030000222
1 H NMR(400MHz,CDCl 3 )δ7.73(s,1H),7.30–7.20(m,2H),7.14(dt,J＝9.8,2.2Hz,1H),6.95–6.90(m,1H),3.58(br,s,2H),3.38(tt,J＝12.0,5.5Hz,1H),2.55(s,3H),2.44(t,J＝12.4Hz,2H),2.24–2.20(m,2H),2.02–1.97(m,2H),1.87(dd,J＝14.6,5.9Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ172.46,161.96(d,J＝246.7Hz),137.07,136.53(d,J＝2.7Hz),132.41(d,J＝8.3Hz),129.61(d,J＝8.6Hz),121.42(d,J＝2.9Hz),113.96(d,J＝21.2Hz),112.44(d,J＝23.0Hz),60.98,37.93,35.32,32.14,24.57ppm.HRMS(EI-TOF)calcd for C 17 H 19 FN 2 S[M + ]m/z 302.1253,found 302.1254.
Figure BDA0003069814030000223
1 H NMR(400MHz,CDCl 3 )δ7.73(s,1H),7.42(t,J＝1.6Hz,1H),7.31(dt,J＝7.3,1.6Hz,1H),7.23(t,J＝7.7Hz,1H),7.19(dt,J＝7.9,1.7Hz,1H),3.53(br,s,2H),3.36(tt,J＝12.0,5.4Hz,1H),2.51(s,3H),2.38(t,J＝12.3Hz,2H),2.21–2.17(m,2H),1.99–1.94(m,2H),1.83(dd,J＝14.6,6.0Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ172.86,137.09,136.19,133.87,132.13,129.25,127.06,125.48,123.81,60.86,38.08,35.53,32.27,24.65ppm.HRMS(EI-TOF)calcd for C 17 H 19 35 ClN 2 S[M + ]m/z 318.0957,found 318.0961.calcd for C 17 H 19 37 ClN 2 S[M + ]m/z 320.0928,found 320.0932.
Figure BDA0003069814030000224
1 H NMR(400MHz,CDCl 3 )δ7.78(s,1H),7.66(s,1H),7.61(d,J＝7.6Hz,1H),7.49–7.41(m,2H),3.67(br,s,2H),3.42(tt,J＝11.8,5.3Hz,1H),2.61–2.52(m,5H),2.27–2.24(m,2H),2.05–2.00(m,2H),1.91(dd,J＝14.5,5.9Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ172.37,137.39,136.35,131.20,130.44(q,J＝32.5Hz),128.91,128.62,123.71(q,J＝3.6Hz),122.78(q,J＝272.5Hz),122.22(q,J＝3.7Hz),61.22,37.78,35.01,31.98,24.42ppm.HRMS(EI-TOF)calcd for C 18 H 19 F 3 N 2 S[M + ]m/z 352.1221,found 352.1223.
Figure BDA0003069814030000231
1 H NMR(400MHz,CDCl 3 )δ7.69(s,1H),7.59(dd,J＝8.0,1.1Hz,1H),7.36(dd,J＝7.7,1.7Hz,1H),7.26(td,J＝7.6,1.2Hz,1H),7.13(td,J＝7.7,1.7Hz,1H),3.58(br,s,2H),3.40(tt,J＝12.0,5.5Hz,1H),2.55(s,3H),2.44(t,J＝12.3Hz,2H),2.24–2.21(m,2H),2.05–1.99(m,2H),1.87(dd,J＝14.7,6.0Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ173.06,140.40,134.89,132.65,131.14,130.98,128.70,126.57,122.02,60.86,37.73,35.13,31.94,24.64ppm.HRMS(EI-TOF)calcd for C 17 H 19 79 BrN 2 S[M + ]m/z 362.0452,found 362.0453.calcd for C 17 H 19 81 BrN 2 S[M + ]m/z 364.0432,found 364.0432.
Figure BDA0003069814030000232
1 H NMR(400MHz,CDCl 3 )δ7.92(s,1H),7.48(d,J＝7.4Hz,1H),7.21(t,J＝7.6Hz,1H),6.91(t,J＝8.9Hz,2H),3.84(s,3H),3.54(br,s,2H),3.38(tt,J＝11.2,5.1Hz,1H),2.53(s,3H),2.39(t,J＝11.8Hz,2H),2.22–2.20(m,2H),2.01–1.96(m,2H),1.87–1.82(m,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ173.17,155.35,139.61,133.57,129.12,128.57,120.98,120.41,111.42,61.76,55.54,38.65,36.19,32.89,25.71ppm.HRMS(EI-TOF)calcd for C 18 H 22 N 2 OS[M + ]m/z 314.1453,found 314.1452.
Figure BDA0003069814030000233
1 H NMR(400MHz,CDCl 3 )δ8.02–8.00(m,1H),7.81–7.77(m,2H),7.65(s,1H),7.44–7.37(m,4H),3.46(br,s,2H),3.43–3.35(m,1H),2.45(s,3H),2.36–2.29(m,2H),2.17–2.13(m,2H),1.99(ddd,J＝13.4,4.6,2.7Hz,2H),1.79(dd,J＝14.5,6.0Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ173.50,139.85,134.49,132.70,130.80,128.06,127.68,127.63,127.40,125.74,125.18,124.20,124.19,60.61,38.11,35.78,32.29,24.81ppm.HRMS(EI-TOF)calcd for C 21 H 22 N 2 S[M + ]m/z 334.1504,found 334.1506.
Figure BDA0003069814030000234
1 H NMR(400MHz,CDCl 3 )δ8.54(d,J＝2.2Hz,1H),7.84(s,1H),7.77(dd,J＝8.3,2.5Hz,1H),7.36(d,J＝8.3Hz,1H),3.44–3.36(m,3H),2.40(s,3H),2.17–2.10(m,4H),2.00–1.94(m,2H),1.77(dd,J＝14.0,5.9Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ176.51,150.60,147.02,138.84,136.31,132.99,126.87,124.45,61.20,39.86,37.75,33.96,26.04ppm.HRMS(EI-TOF)calcd for C 16 H 18 35 ClN 3 S[M + ]m/z 319.0910,found 319.0912.calcd for C 16 H 18 37 ClN 3 S[M + ]m/z 321.0880,found 321.0881.
Figure BDA0003069814030000241
1 H NMR(400MHz,CDCl 3 )δ7.77(s,1H),7.38(s,1H),7.34(d,J＝8.3Hz,1H),7.30–7.27(m,1H),3.99(br,s,2H),3.57(tt,J＝12.1,5.3Hz,1H),2.96–2.89(m,2H),2.85(s,3H),2.45–2.42(m,2H),2.40(s,3H),2.21–2.11(m,4H)ppm. 13 C NMR(101MHz,CDCl 3 )δ170.76,138.55,137.62,136.87,134.42,129.64,129.59,129.12,125.26,63.02,34.52,32.38,29.68,25.11,20.02ppm.HRMS(EI-TOF)calcd for C 18 H 21 35 ClN 2 S[M + ]m/z 332.1114,found 332.1112.calcd for C 18 H 21 37 ClN 2 S[M + ]m/z 334.1084,found 334.1092.
Figure BDA0003069814030000242
1 H NMR(400MHz,CDCl 3 )δ7.70(s,1H),7.33–7.26(m,2H),7.00(t,J＝8.9Hz,1H),3.40–3.31(m,3H),2.37(s,3H),2.30(s,3H),2.15–2.04(m,4H),1.94(ddd,J＝13.4,5.1,3.2Hz,2H),1.74(dd,J＝14.4,6.3Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ174.9,161.1(d,J＝246.8Hz),137.3,137.1(d,J＝0.9Hz),129.7(d,J＝5.3Hz),127.5(d,J＝3.8Hz),125.6(d,J＝8.1Hz),125.5(d,J＝17.8Hz)115.6(d,J＝22.9Hz),61.1,39.9,37.9,33.9,26.1,14.5(d,J＝3.4Hz)ppm.HRMS(EI-TOF)calcd for C 18 H 21 FN 2 S[M + ]m/z 316.1409,found 316.1408.
Figure BDA0003069814030000243
1 H NMR(400MHz,CDCl 3 )δ7.77(s,1H),7.50(d,J＝8.3Hz,1H),7.36(d,J＝1.9Hz,1H),7.18(dd,J＝8.2,2.1Hz,1H),3.40–3.32(m,3H),2.41(s,3H),2.38(s,3H),2.15–2.06(m,4H),1.94(ddd,J＝12.9,4.6,2.7Hz,2H),1.74(dd,J＝14.4,6.3Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ175.20,138.55,137.57,137.11,132.84,130.78,128.70,125.32,124.39,61.15,39.85,37.78,33.95,26.12,22.91ppm.HRMS(EI-TOF)calcd for C 18 H 21 79 BrN 2 S[M + ]m/z 376.0609,found 376.0611.calcd for C 18 H 21 81 BrN 2 S[M + ]m/z 378.0588,found 378.0590.
Figure BDA0003069814030000244
1 H NMR(400MHz,CDCl 3 )δ7.72(s,1H),7.28–7.27(m,1H),7.22–7.20(m,2H),7.08(d,J＝7.4Hz,1H),3.54(br,s,2H),3.37(tt,J＝12.0,5.4Hz,1H),2.60(q,J＝7.6Hz,2H),2.52(s,3H),2.38(t,J＝13.4Hz,2H),2.21–2.18(m,2H),2.01–1.96(m,2H),1.85(dd,J＝14.6,5.9Hz,2H),1.19(t,J＝7.6Hz,3H)ppm. 13 C NMR(101MHz,CDCl 3 )δ171.81,144.12,138.05,136.23,130.29,127.98,126.78,125.29,123.03,60.81,37.89,35.45,32.19,27.77,24.65,14.55ppm.HRMS(EI-TOF)calcd for C 19 H 24 N 2 S[M + ]m/z 312.1660,found 312.1661.
Figure BDA0003069814030000251
1 H NMR(400MHz,CDCl 3 )δ7.72(s,1H),7.29–7.28(m,1H),7.26–7.25(m,1H),7.20(s,1H),7.13–7.10(m,1H),3.49(br,s,2H),3.36(tt,J＝11.9,5.3Hz,1H),2.86(hept,J＝6.9Hz,1H),2.48(s,3H),2.33–2.27(m,2H),2.19–2.15(m,2H),1.99–1.93(m,2H),1.81(dd,J＝14.6,6.0Hz,2H),1.20(d,J＝6.9Hz,6H)ppm. 13 C NMR(101MHz,CDCl 3 )δ172.15,148.75,138.01,136.23,130.31,127.99,125.28,123.95,123.21,60.66,38.07,35.68,33.08,32.30,24.74,22.90ppm.HRMS(EI-TOF)calcd for C 20 H 26 N 2 S[M + ]m/z 326.1817,found 326.1819.
Figure BDA0003069814030000252
1 H NMR(400MHz,CDCl 3 )δ7.75(s,1H),7.45(d,J＝8.4Hz,2H),7.39(d,J＝8.4Hz,2H),3.39–3.28(m,3H),2.36(s,3H),2.13–2.08(m,2H),2.06–2.02(m,2H),1.93(ddd,J＝13.2,4.9,2.9Hz,2H),1.72(dd,J＝14.3,6.2Hz,2H),1.33(s,9H)ppm. 13 C NMR(101MHz,CDCl 3 )δ174.8,151.2,138.1,137.0,128.8,126.4,125.9,61.1,39.9,37.9,34.6,34.0,31.2,26.2ppm.HRMS(EI-TOF)calcd for C 21 H 28 N 2 S[M + ]m/z 340.1973,found 340.1974.
Figure BDA0003069814030000253
1 H NMR(400MHz,CDCl 3 )δ7.79(s,1H),7.70(dt,J＝8.9,1.8Hz,2H),7.25(dt,J＝8.7,2.1Hz,2H),3.40–3.33(m,3H),2.38(s,3H),2.16–2.06(m,4H),1.94(ddd,J＝12.9,4.7,2.9Hz,2H),1.75(dd,J＝14.2,6.4Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ175.5,138.1,137.8,137.1,131.2,128.2,93.3,61.1,39.8,37.7,34.0,26.1ppm.HRMS(EI-TOF)calcd for C 17 H 19 IN 2 S[M + ]m/z 410.0314,found 410.0316.
Figure BDA0003069814030000254
1 H NMR(400MHz,CDCl 3 )δ7.74(s,1H),7.56(d,J＝1.6Hz,1H),7.46(d,J＝8.6Hz,1H),7.21(dd,J＝8.6,1.1Hz,1H),3.39(tt,J＝11.9,5.7Hz,1H),3.31(br,s,2H),2.36(s,3H),2.15–2.10(m,2H),2.08–2.04(m,2H),1.97(ddd,J＝13.1,5.0,3.0Hz,2H),1.73(dd,J＝14.4,6.1Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ177.0,148.8(q,J＝2.0Hz),141.7,133.9,132.6,131.4,126.0,123.4,120.3(q,J＝258.9Hz),119.9,61.1,40.0,38.0,33.9,26.2ppm.HRMS(EI-TOF)calcd for C 18 H 18 79 BrF 3 N 2 OS[M + ]m/z 446.0275,found 446.0276.calcd for C 18 H 18 81 BrF 3 N 2 OS[M + ]m/z 448.0255,found 448.0254.
Figure BDA0003069814030000261
1 H NMR(400MHz,CDCl 3 )δ7.79(s,1H),7.78(s,1H),7.46(dd,J＝8.5,2.0Hz,1H),7.31(d,J＝8.4Hz,1H),3.41–3.32(m,3H),2.37(s,3H),2.16–2.04(m,4H),1.97–1.92(m,2H),1.73(dd,J＝14.1,6.2Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ176.5,145.9(q,J＝1.5Hz),138.6,135.1,132.0,131.7,126.7,122.6,120.4(q,J＝259.6Hz),116.7,61.1,39.9,37.9,34.1,26.1ppm.HRMS(EI-TOF)calcd for C 18 H 18 79 BrF 3 N 2 OS[M + ]m/z 446.0275,found 446.0273.calcd for C 18 H 18 81 BrF 3 N 2 OS[M + ]m/z 448.0255,found 448.0258.
Figure BDA0003069814030000262
1 H NMR(400MHz,CDCl 3 )δ7.76(s,1H),7.20(s,2H),3.38–3.31(m,1H),3.29–3.27(m,2H),2.42(s,6H),2.34(s,3H),2.13–2.09(m,2H),2.03(td,J＝12.9,2.4Hz,1H),1.92(ddd,J＝13.2,5.3,3.2Hz,2H),1.71(dd,J＝14.3,6.2Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ175.3,138.9,137.4,137.1,130.0,126.1,61.0,39.9,37.9,34.0,26.2,23.8ppm.HRMS(EI-TOF)calcd for C 19 H 23 79 BrN 2 S[M + ]m/z 390.0765,found 390.0764.calcd for C 19 H 23 81 BrN 2 S[M + ]m/z 392.0745,found 392.0747.
Figure BDA0003069814030000263
1 H NMR(400MHz,CDCl 3 )δ7.80(s,1H),7.50(d,J＝8.6Hz,1H),7.37(d,J＝1.7Hz,2H),7.17(ddd,J＝8.6,2.3,1.0Hz,1H),3.39(tt,J＝11.9,5.7Hz,1H),3.32–3.30(m,2H),2.37(s,3H),2.15–2.11(m,2H),2.06(dd,J＝12.5,2.0Hz,2H),1.96(ddd,J＝13.3,5.4,3.3Hz,2H),1.74(dd,J＝14.5,6.2Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ177.1,148.8(d,J＝1.8Hz),141.7,133.5,132.4,132.2,129.4,122.9,120.3(q,J＝258.8Hz),119.5,61.1,39.9,37.9,33.9,26.2ppm.HRMS(EI-TOF)calcd for C 18 H 18 35 ClF 3 N 2 OS[M + ]m/z 402.0780,found 402.0782.calcd for C 18 H 18 37 ClF 3 N 2 OS[M + ]m/z 404.0751,found 404.0751.
Figure BDA0003069814030000264
1 H NMR(400MHz,CDCl 3 )δ7.84(s,1H),7.62–7.57(m,6H),7.45(t,J＝7.6Hz,2H),7.36(t,J＝7.3Hz,1H),3.42–3.34(m,1H),3.31–3.30(m,2H),2.37(s,3H),2.14–2.11(m,2H),2.07–2.04(m,2H),1.95(ddd,J＝13.3,5.1,3.1Hz,2H),1.73(dd,J＝14.3,6.3Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ175.30,140.78,140.28,137.82,137.38,130.62,128.86,127.64,127.56,126.95,126.92,61.09,39.98,38.01,34.08,26.23ppm.HRMS(EI-TOF)calcd for C 23 H 24 N 2 S[M + ]m/z 360.1660,found 360.1663.
Figure BDA0003069814030000271
1 H NMR(400MHz,CDCl 3 )δ7.87(s,1H),7.73(s,1H),7.62(d,J＝7.4Hz,2H),7.54–7.46(m,5H),7.39(t,J＝7.3Hz,1H),3.39(tt,J＝12.0,5.7Hz,1H),3.31(br,s,2H),2.38(s,3H),2.16–2.11(m,2H),2.08–2.05(m,2H),1.97(ddd,J＝13.1,4.7,2.8Hz,2H),1.74(dd,J＝14.4,6.2Hz,3H)ppm. 13 C NMR(101MHz,CDCl 3 )δ175.35,142.12,140.57,138.06,137.57,132.14,129.43,128.86,127.65,127.18,126.87,125.50,125.46,61.11,39.94,37.93,34.06,26.23ppm.HRMS(EI-TOF)calcd for C 23 H 24 N 2 S[M + ]m/z 360.1660,found 360.1662.
Figure BDA0003069814030000272
1 H NMR(400MHz,CDCl 3 )δ7.86(s,1H),7.73–7.67(m,1H),7.63–7.61(m,1H),7.55–7.37(m,6H),3.43–3.36(m,1H),3.32(br,s,2H),2.39(s,3H),2.16–2.13(m,2H),2.09–2.06(m,2H),2.00–1.94(m,2H),1.75(dd,J＝14.2,6.1Hz,2H)ppm.HRMS(EI-TOF)calcd for C 23 H 23 35 ClN 2 S[M + ]m/z 394.1270,found 394.1272.calcd for C 23 H 23 37 ClN 2 S[M + ]m/z 396.1241,found 396.1249.
Figure BDA0003069814030000273
1 H NMR(400MHz,CDCl 3 )δ7.72(s,1H),7.49–7.45(m,2H),7.38–7.32(m,2H),7.15–7.11(m,1H),7.05–7.04(m,1H),7.03–7.01(m,2H),7.00–6.99(m,1H),3.39–3.32(m,1H),3.29–3.27(m,2H),2.35(s,3H),2.13–2.10(m,2H),2.04(td,J＝12.9,2.3Hz,2H),1.93(ddd,J＝13.3,5.3,3.2Hz,2H),1.72(dd,J＝14.4,6.3Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ174.95,157.31,156.73,138.76,137.56,136.92,129.84,128.06,123.65,119.13,119.09,61.07,40.03,38.08,34.05,26.23ppm.HRMS(EI-TOF)calcd for C 23 H 24 N 2 OS[M + ]m/z 376.1609,found 376.1612.
Figure BDA0003069814030000274
1 H NMR(400MHz,CDCl 3 )δ7.86(d,J＝3.7Hz,1H),7.62(d,J＝5.0Hz,1H),7.18(t,J＝4.4Hz,1H),4.39–4.30(m,2H),3.39(tt,J＝11.9,5.3Hz,1H),2.11–2.05(m,4H),1.93–1.87(m,2H),1.78(dd,J＝14.1,6.5Hz,2H),1.49(s,9H)ppm. 13 C NMR(101MHz,CDCl 3 )δ173.51,171.07,153.35,131.77,131.65,128.43,125.92,79.40,53.46,52.72,35.08,34.60,28.52,28.29,27.71,27.62ppm.HRMS(EI-TOF)calcd for C 18 H 23 N 3 O 3 S[M + ]m/z 361.1460,found 361.1462.
Figure BDA0003069814030000281
1 H NMR(400MHz,CDCl 3 )δ8.17–8.14(m,2H),7.35(d,J＝8.2Hz,2H),4.39–4.32(m,2H),3.47–3.38(m,1H),2.16–2.07(m,4H),1.92–1.88(m,2H),1.83–1.78(m,2H),1.50(s,9H)ppm. 13 C NMR(101MHz,CDCl 3 )δ174.20,173.76,153.35,152.23(q,J＝1.6 Hz),129.90,122.77,121.05,120.26(q,J＝258.9Hz),79.37,53.45,52.75,35.01,34.66,28.48,28.27,27.67,27.58ppm.HRMS(EI-TOF)calcd for C 21 H 24 F 3 N 3 O 4 [M + ]m/z 439.1719,found 439.1723.
Figure BDA0003069814030000282
1 H NMR(400MHz,CDCl 3 )δ8.18(d,J＝8.0Hz,2H),7.74(d,J＝8.1Hz,2H),4.37–4.28(m,2H),3.41(tt,J＝11.8,5.2Hz,1H),2.10–2.04(m,4H),1.90–1.85(m,2H),1.80–1.74(m,2H),1.46(s,9H)ppm. 13 C NMR(101MHz,CDCl 3 )δ174.10,173.90,153.36,134.13(q,J＝32.9Hz),128.39,127.44(q,J＝1.1Hz),126.07(q,J＝3.7Hz),123.45(q,J＝272.7Hz),79.41,53.43,52.75,34.96,34.63,28.49,28.31,27.70,27.65ppm.HRMS(EI-TOF)calcd for C 21 H 24 F 3 N 3 O 3 [M + ]m/z 423.1770,found 423.1767.
Figure BDA0003069814030000283
1 H NMR(400MHz,CDCl 3 )δ7.80–7.79(m,1H),7.57–7.56(m,1H),7.13–7.10(m,1H),3.62(br,s,2H),3.23–3.14(m,1H),2.60(s,3H),2.48–2.39(m,2H),2.29–2.26(m,2H),1.97–1.85(m,4H)ppm. 13 C NMR(101MHz,CDCl 3 )δ172.48,171.25,131.99,131.85,128.48,125.62,61.27,38.27,32.81,26.32,25.60ppm.HRMS(EI-TOF)calcd for C 14 H 17 N 3 OS[M + ]m/z 275.1092,found 275.1093.
Figure BDA0003069814030000284
1 H NMR(400MHz,CDCl 3 )δ7.93(s,1H),7.91–7.89(m,1H),7.41–7.36(m,2H),3.31–3.29(m,2H),3.19(tt,J＝12.0,5.5Hz,1H),2.42(s,3H),2.37(s,3H),2.19–2.12(m,4H),1.82(ddd,J＝13.6,5.2,3.3Hz,2H),1.75–1.69(m,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ175.45,173.97,138.86,133.30,128.88,128.51,125.13,124.26,60.61,39.71,34.63,27.16,26.21,21.24ppm.HRMS(EI-TOF)calcd for C 17 H 21 N 3 O[M + ]m/z 283.1685,found 283.1683.
Figure BDA0003069814030000291
1 H NMR(400MHz,CDCl 3 )δ8.17(d,J＝8.8Hz,2H),7.36(d,J＝8.2Hz,2H),3.41(br,s,2H),3.23(tt,J＝11.8,5.4Hz,1H),2.45(s,3H),2.28–2.18(m,4H),1.90–1.84(m,2H),1.79(dd,J＝14.5,6.1Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ174.21,173.83,152.23(q,J＝1.7Hz),129.95,122.78,121.07,120.27(q,J＝259.0Hz),60.84,39.49,34.31,26.88,26.01ppm.HRMS(EI-TOF)calcd for C 17 H 18 F 3 N 3 O 2 [M + ]m/z 353.1351,found 353.1352.
Figure BDA0003069814030000292
1 H NMR(400MHz,CDCl 3 )δ8.21(d,J＝8.3Hz,2H),7.75(d,J＝8.4Hz,2H),3.33–3.30(m,2H),3.20(tt,J＝12.0,5.5Hz,1H),2.36(s,3H),2.19–2.12(m,4H),1.81(ddd,J＝13.5,5.0,3.1Hz,2H),1.72(dd,J＝14.6,6.3Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ174.24,173.95,134.00(q,J＝32.9Hz),128.37,127.47,126.02(q,J＝3.7Hz),123.45(q,J＝272.7Hz),60.66,39.78,34.69,27.04,26.08ppm.HRMS(EI-TOF)calcd for C 17 H 18 F 3 N 3 O[M + ]m/z 337.1402,found 337.1400.
Figure BDA0003069814030000293
1 H NMR(400MHz,CDCl 3 )δ8.01(d,J＝8.5Hz,2H),7.46(d,J＝8.5Hz,2H),3.33(br,s,2H),3.18(tt,J＝11.9,5.5Hz,1H),2.38(s,3H),2.20–2.12(m,4H),1.84–1.78(m,2H),1.72(dd,J＝14.3,6.1Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ204.82,174.39,173.95,138.93,129.39,129.28,122.78,60.70,39.66,34.52,26.98,26.08ppm.HRMS(EI-TOF)calcd for C 16 H 18 35 ClN 3 O[M + ]m/z 303.1138,found 303.1139.calcd for C 16 H 18 37 ClN 3 O[M + ]m/z 305.1109,found 305.1116.
Figure BDA0003069814030000294
1 H NMR(400MHz,CDCl 3 )δ8.09(dt,J＝9.5,2.7Hz,2H),7.42(d,J＝7.1Hz,2H),7.35–7.31(m,4H),7.27–7.25(m,1H),3.62(s,2H),3.41–3.33(m,3H),2.21–2.14(m,4H),1.87(ddd,J＝13.3,5.1,3.4Hz,2H),1.74(dd,J＝14.6,6.4Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ169.87,163.55,151.38,139.49,128.83,128.57,128.53,128.36,128.26,126.93,122.68,121.25,121.20,120.33(q,J＝258.6Hz),58.57,56.51,35.09,27.43,26.42ppm.HRMS(EI-TOF)calcd for C 23 H 22 F 3 N 3 O 2 [M + ]m/z 429.1664,found 429.1666.
Figure BDA0003069814030000301
1 H NMR(400MHz,CDCl 3 )δ8.20(d,J＝8.1Hz,2H),7.87(dd,J＝6.4,2.7Hz,2H),7.74(d,J＝8.3Hz,2H),7.46–7.40(m,3H),4.20(d,J＝6.4Hz,2H),3.93(s,2H),3.66–3.58(m,1H),3.28(t,J＝12.9Hz,2H),2.47–2.45(m,2H),2.18–2.10(m,4H)ppm. 13 C NMR(101MHz,CDCl 3 )δ167.16,164.14,133.27(q,J＝32.9Hz),131.03,130.11,129.40,128.77,127.40,126.29(q,J＝272.9Hz),126.73,126.05(q,J＝3.7Hz),60.25,55.28,32.60,26.27,24.84ppm.HRMS(EI-TOF)calcd for C 23 H 22 F 3 N 3 O[M + ]m/z 413.1715,found 413.1714.
Figure BDA0003069814030000302
1 H NMR(400MHz,CDCl 3 )δ8.07(d,J＝8.8Hz,2H),7.34(d,J＝8.3Hz,2H),3.43–3.34(m,3H),2.40(s,3H),2.29–2.17(m,4H),1.90(ddd,J＝13.0,4.4,2.7Hz,4H),1.75(dd,J＝14.6,6.3Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ169.27,163.67,151.42(q,J＝2.0Hz),128.56,122.54,121.19,120.29(q,J＝258.8Hz),60.77,40.05,34.59,26.79,25.86ppm.HRMS(EI-TOF)calcd for C 17 H 18 F 3 N 3 O 2 [M + ]m/z 353.1351,found 353.1349.
Figure BDA0003069814030000303
1 H NMR(400MHz,CDCl 3 )δ7.85(s,1H),7.81(d,J＝7.6Hz,1H),7.37(t,J＝7.6Hz,1H),7.32(d,J＝7.7Hz,1H),3.41–3.32(m,3H),2.42(s,3H),2.37(s,3H),2.23–2.14(m,4H),1.87(ddd,J＝13.5,5.1,3.3Hz,2H),1.72(dd,J＝14.5,6.2Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ169.05,164.85,138.83,132.30,128.87,127.30,123.88,60.70,40.21,34.83,26.90,25.95,21.28ppm.HRMS(EI-TOF)calcd for C 17 H 21 N 3 O[M + ]m/z 283.1685,found 283.1684.
Figure BDA0003069814030000304
1 H NMR(400MHz,CDCl 3 )δ7.90(d,J＝8.9Hz,2H),6.94(d,J＝8.9Hz,2H),3.82(s,3H),3.34–3.26(m,3H),2.31(s,3H),2.15–2.08(m,4H),1.84–1.79(m,2H),1.66(dd,J＝14.2,6.1Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ168.63,164.62,162.14,128.49,116.59,114.39,60.69,55.42,40.14,34.77,26.86,25.97ppm.HRMS(EI-TOF)calcd for C 17 H 21 N 3 O 2 [M + ]m/z 299.1634,found 299.1630.
Figure BDA0003069814030000311
1 H NMR(400MHz,CDCl 3 )δ8.01(d,J＝6.6Hz,2H),7.49(d,J＝6.4Hz,2H),3.40–3.33(m,3H),2.37(s,3H),2.23–2.14(m,4H),1.90–1.85(m,2H),1.75–1.70(m,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ169.12,164.67,131.49,128.95,126.73,124.01,60.67,40.10,34.68,26.86,25.95ppm.HRMS(EI-TOF)calcd for C 16 H 18 ClN 3 O[M + ]m/z,found.
Figure BDA0003069814030000312
1 H NMR(400MHz,CDCl 3 )δ8.15(d,J＝8.2Hz,2H),7.76(d,J＝8.3Hz,2H),3.43–3.34(m,3H),2.38(s,3H),2.24–2.16(m,4H),1.90(ddd,J＝12.8,4.6,2.8Hz,2H),1.73(dd,J＝14.6,6.3Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ169.79,163.57,133.15(q,J＝32.7Hz),127.25,127.08,126.04(q,J＝3.8Hz),123.55(d,J＝272.7Hz),60.71,40.22,34.80,26.92,25.92ppm.HRMS(EI-TOF)calcd for C 17 H 18 F 3 N 3 O[M + ]m/z 337.1402,found 337.1403.
Figure BDA0003069814030000313
1 H NMR(400MHz,DMSO-d 6 )δ8.22(d,J＝8.1Hz,2H),7.99(d,J＝8.1Hz,2H),4.07(br,s,2H),3.80(tt,J＝12.1,6.5Hz,1H),3.24(s,3H),3.11(s,3H),2.53–2.50(m,2H),2.43–2.40(m,2H),2.27–2.19(m,4H)ppm. 13 C NMR(101MHz,DMSO-d 6 )δ168.13,162.98,131.47(q,J＝32.4Hz),127.31,127.10,126.41(q,J＝3.6Hz),123.67(q,J＝272.4Hz),67.54,50.32,43.54,28.69,24.53,22.58ppm.HRMS(ESI-TOF)calcd for C 18 H 21 F 3 N 3 O[M + ]m/z 352.1637,found 352.1638.
Figure BDA0003069814030000314
1 H NMR(400MHz,CDCl 3 )δ7.97(d,J＝8.7Hz,2H),7.31(d,J＝8.6Hz,2H),3.58(tt,J＝11.8,5.6Hz,1H),3.36(br,s,2H),2.39(s,3H),2.19–2.12(m,4H),2.04–1.97(m,2H),1.79(dd,J＝14.4,6.0Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ175.39,166.65,150.93,129.37,128.88,128.54,121.29,121.20,120.32(q,J＝258.3Hz),61.30,40.12,38.51,31.39,25.94ppm.HRMS(EI-TOF)calcd for C 17 H 18 F 3 N 3 OS[M + ]m/z 369.1123,found 369.1122.
Figure BDA0003069814030000315
1 H NMR(400MHz,CDCl 3 )δ7.75(s,1H),7.69(d,J＝7.6Hz,1H),7.34(t,J＝7.6Hz,1H),7.27(d,J＝8.2Hz,1H),3.57(tt,J＝11.9,5.6Hz,1H),3.35(br,s,2H),2.41(s,3H),2.39(s,3H),2.17–2.10(m,4H),2.02–1.96(m,2H),1.78(dd,J＝14.4,6.3Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ174.80,168.42,138.90,131.67,130.16,128.94,128.29,125.06,61.27,40.07,38.46,31.36,25.97,21.29ppm.HRMS(EI-TOF)calcd for C 17 H 21 N 3 S[M + ]m/z 299.1456,found 299.1457.
Figure BDA0003069814030000321
1 H NMR(400MHz,CDCl 3 )δ8.16(d,J＝8.2Hz,2H),7.76(d,J＝8.3Hz,2H),3.50(s,2H),3.48–3.38(m,1H),2.49(s,3H),2.42(t,J＝12.3Hz,2H),2.28–2.20(m,2H),2.01–1.93(m,2H),1.83(dd,J＝14.6,6.2Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ169.15,163.69,133.19(q,J＝32.9Hz),128.12,127.14,126.05(q,J＝3.7Hz),123.53(q,J＝272.9Hz),61.06,39.74,34.11,26.58,25.66ppm.HRMS(EI-TOF)calcd for C 17 H 18 F 3 N 3 S[M + ]m/z 353.1174,found 353.1175.
Figure BDA0003069814030000322
1 H NMR(400MHz,CDCl 3 )δ7.83(dt,J＝9.6,2.8Hz,2H),7.54(d,J＝2.4Hz,1H),7.41–7.30(m,5H),7.23(d,J＝8.1Hz,2H),6.56(d,J＝2.4Hz,1H),5.18(s,2H),4.41–4.37(m,3H),2.62–2.43(m,4H),1.90–1.86(m,2H),1.75–1.73(m,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ153.60,149.06,148.57(q,J＝1.7Hz),136.89,132.56,129.46,128.53,128.04,127.92,126.77,121.16,120.52(q,J＝256.7Hz),102.91,66.82,52.80,51.99,34.63,33.98,28.46,27.77ppm.HRMS(EI-TOF)calcd for C 25 H 24 F 3 N 3 O 3 [M + ]m/z 471.1770,found 471.1772.
Figure BDA0003069814030000323
1 H NMR(400MHz,CDCl 3 )δ7.92(d,J＝8.1Hz,2H),7.63(d,J＝8.2Hz,2H),7.56(d,J＝2.4Hz,1H),7.41–7.30(m,5H),6.63(d,J＝2.4Hz,1H),5.18(s,2H),4.43–4.38(m,3H),2.62–2.43(m,4H),1.91–1.87(m,2H),1.76–1.71(m,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ153.60,148.89,137.12(q,J＝2.7Hz),136.87,129.58,129.27(q,J＝32.4Hz),128.54,128.05,127.92,125.55(q,J＝3.9Hz),125.54,124.27(q,J＝271.8Hz),103.38,66.83,52.93,51.97,34.64,34.01,28.48,27.78ppm.HRMS(EI-TOF)calcd for C 25 H 24 F 3 N 3 O 2 [M + ]m/z 455.1821,found 455.1823.
Figure BDA0003069814030000331
1 H NMR(400MHz,CDCl 3 )δ7.84(d,J＝8.7Hz,2H),7.56(d,J＝2.2Hz,1H),7.23(d,J＝8.2Hz,2H),6.54(d,J＝2.2Hz,1H),4.41(tt,J＝6.5,2.6Hz,1H),3.21(br,s,2H),2.56–2.44(m,4H),2.30(s,3H),1.94–1.91(m,2H),1.63(dd,J＝14.2,6.3Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ148.87,148.44(q,J＝1.5Hz),132.82,129.29,126.72,121.11,120.52(q,J＝256.9Hz),102.54,59.53,52.13,40.19,35.16,25.62ppm.HRMS(EI-TOF)calcd for C 18 H 20 F 3 N 3 O[M + ]m/z 351.1558,found 351.1559.
Figure BDA0003069814030000332
1 H NMR(400MHz,CDCl 3 )δ7.65(s,1H),7.61(d,J＝7.7Hz,1H),7.54(d,J＝2.3Hz,1H),7.27(t,J＝7.6Hz,1H),7.09(d,J＝7.5Hz,1H),6.54(d,J＝2.3Hz,1H),4.40(tt,J＝7.0,2.7Hz,1H),3.20–3.17(m,2H),2.58–2.54(m,2H),2.47–2.42(m,2H),2.39(s,3H),2.28(s,3H),1.93–1.89(m,2H),1.65–1.59(m,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ150.27,138.06,133.88,128.89,128.45,128.10,126.10,122.64,102.43,59.54,52.05,40.23,35.13,25.64,21.52ppm.HRMS(EI-TOF)calcd for C 18 H 23 N 3 [M + ]m/z 281.1892,found 281.1894.
Figure BDA0003069814030000333
1 H NMR(400MHz,CDCl 3 )δ7.75(d,J＝8.7Hz,2H),7.53(d,J＝1.9Hz,1H),6.92(d,J＝8.6Hz,2H),6.48(d,J＝2.1Hz,1H),4.41–4.36(m,1H),3.83(s,3H),3.19(br,s,2H),2.57–2.53(m,2H),2.48–2.41(m,2H),2.29(s,3H),1.93–1.90(m,2H),1.65(dd,J＝14.0,6.3Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ159.08,150.00,128.90,126.90,126.67,113.95,101.86,59.56,55.30,51.89,40.20,35.10,25.61ppm.HRMS(EI-TOF)calcd for C 18 H 23 N 3 O[M + ]m/z 297.1841,found 297.1842.
Figure BDA0003069814030000334
1 H NMR(400MHz,CDCl 3 )δ7.83(d,J＝7.7Hz,2H),7.55(d,J＝1.7Hz,1H),7.38(t,J＝7.6Hz,2H),6.56(d,J＝2.1Hz,1H),4.42–4.39(m,1H),3.21(br,s,2H),2.58–2.54(m,2H),2.50–2.43(m,2H),2.30(s,3H),1.93–1.90(m,2H),1.66(dd,J＝14.1,6.3Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ150.13,133.97,129.02,128.54,127.32,125.44,102.46,59.57,51.98,40.16,35.07,25.57ppm.HRMS(EI-TOF)calcd for C 17 H 20 35 ClN 3 [M + ]m/z 301.1346,found 301.1343.calcd for C 17 H 20 37 ClN 3 [M + ]m/z 303.1316,found 303.1317.
Figure BDA0003069814030000335
1 H NMR(400MHz,CDCl 3 )δ7.93(d,J＝8.2Hz,2H),7.63(d,J＝8.2Hz,2H),7.59(d,J＝2.1Hz,1H),6.62(d,J＝2.2Hz,1H),4.45–4.40(m,1H),3.22(br,s,2H),2.57–2.45(m,4H),2.30(s,3H),1.95–1.92(m,2H),1.63(dd,J＝14.2,6.4Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ148.71,137.37,129.42,129.08(q,J＝32.3Hz),125.49,125.48(q,J＝4.2Hz),124.35(q,J＝271.8Hz),103.02,59.51,52.27,40.20,35.19,25.62ppm.HRMS(EI-TOF)calcd for C 18 H 20 F 3 N 3 [M + ]m/z 335.1609,found 335.1612.
Figure BDA0003069814030000341
1 H NMR(400MHz,CDCl 3 )δ7.81–7.79(m,2H),7.55(d,J＝2.2Hz,1H),7.28–7.25(m,2H),7.02(d,J＝8.6Hz,2H),6.96–6.92(m,2H),6.52(d,J＝2.2Hz,1H),4.42–4.37(m,1H),3.20(br,s,2H),2.57–2.53(m,2H),2.49–2.42(m,2H),2.29(s,3H),1.94–1.90(m,2H),1.66–1.61(m,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ156.19,156.03,149.50,129.88,129.67,129.15,128.01,127.00,119.76,119.29,102.23,59.56,52.05,40.27,35.17,25.64ppm.HRMS(EI-TOF)calcd for C 23 H 24 35 ClN 3 O[M + ]m/z 393.1608,found 393.1610.calcd for C 23 H 24 37 ClN 3 O[M + ]m/z 395.1578,found 395.1581.
Figure BDA0003069814030000342
1 H NMR(400MHz,CDCl 3 )δ7.52(d,J＝2.2Hz,1H),7.35(d,J＝1.5Hz,1H),7.28(dd,J＝8.1,1.6Hz,1H),6.83(d,J＝8.1Hz,1H),6.45(d,J＝2.3Hz,1H),5.96(s,2H),4.37(tt,J＝6.9,2.6Hz,1H),3.18(br,s,2H),2.55–2.51(m,2H),2.46–2.39(m,2H),2.28(s,3H),1.93–1.90(m,2H),1.62(dd,J＝14.2,6.2Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ149.88,147.86,146.92,128.99,128.45,119.00,108.37,106.17,101.98,100.93,59.50,52.02,40.30,35.20,25.65ppm.HRMS(EI-TOF)calcd for C 18 H 21 N 3 O 2 [M + ]m/z 311.1634,found 311.1632.
Figure BDA0003069814030000343
1 H NMR(400MHz,CDCl 3 )δ7.81–7.78(m,2H),7.55(d,J＝2.3Hz,1H),7.35–7.31(m,2H),7.11–7.07(m,1H),7.07–7.01(m,4H),6.51(d,J＝2.3Hz,1H),4.40(tt,J＝6.9,2.7Hz,1H),3.20(br,s,2H),2.57–2.52(m,2H),2.48–2.42(m,2H),2.29(s,3H),1.94–1.91(m,2H),1.65(dd,J＝14.3,6.3Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ157.47,156.44,149.66,129.70,129.47,129.08,126.90,123.06,119.25,118.61,102.18,59.54,52.03,40.26,35.17,26.92,25.63ppm.HRMS(EI-TOF)calcd for C 23 H 25 N 3 O[M + ]m/z 359.1998,found 359.1999.
Figure BDA0003069814030000351
1 H NMR(400MHz,CDCl 3 )δ7.87(d,J＝8.7Hz,2H),7.56(d,J＝2.2Hz,1H),7.30(d,J＝8.7Hz,2H),7.25(d,J＝3.8Hz,1H),6.81(d,J＝3.8Hz,1H),6.54(d,J＝2.3Hz,1H),4.40(tt,J＝6.8,2.8Hz,1H),3.19(br,s,2H),2.56–2.52(m,2H),2.48–2.41(m,2H),2.29(s,3H),1.94–1.91(m,2H),1.63(dd,J＝14.2,6.3Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ174.14,154.73,149.16,137.67,132.00,129.20,126.98,120.35,112.87,102.44,59.49,52.16,40.32,35.26,25.65ppm.HRMS(EI-TOF)calcd for C 20 H 22 N 4 OS[M + ]m/z 366.1514,found 366.1510.
Figure BDA0003069814030000352
1 H NMR(400MHz,CDCl 3 )δ8.03(d,J＝4.8Hz,1H),7.87(d,J＝8.6Hz,2H),7.76(d,J＝7.7Hz,1H),7.55(d,J＝2.0Hz,1H),7.18(d,J＝8.6Hz,2H),6.96(dd,J＝7.5,4.9Hz,1H),6.55(d,J＝2.2Hz,1H),4.44–4.39(m,1H),3.23(br,s,2H),2.60–2.56(m,2H),2.51–2.45(m,2H),2.31(s,3H),1.94–1.91(m,2H),1.67(dd,J＝14.0,6.3Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ159.16,152.84,149.53,145.19,139.24,131.13,129.06,126.67,121.57,119.18,119.06,102.45,59.61,51.90,40.13,34.99,25.45ppm.HRMS(EI-TOF)calcd for C 22 H 23 35 ClN 4 O[M + ]m/z 394.1560,found 394.1558.calcd for C 22 H 23 37 ClN 4 O[M + ]m/z 396.1531,found 396.1530.
Figure BDA0003069814030000353
1 H NMR(400MHz,CDCl 3 )δ7.86(s,1H),7.83(s,1H),7.62–7.57(m,4H),4.42–4.27(m,3H),2.57–2.45(s,4H),1.91–1.84(m,2H),1.69–1.61(m,2H),1.51(s,9H)ppm. 13 C NMR(101MHz,CDCl 3 )δ153.53,136.23(q,J＝1.3Hz),136.15,128.27(q,J＝32.4Hz),125.84(q,J＝3.7Hz),125.47,125.44,124.25(q,J＝271.9Hz),79.62,53.21,51.88,51.12,34.53,34.13,28.76,28.51,28.27ppm.HRMS(EI-TOF)calcd for C 22 H 26 F 3 N 3 O 2 [M + ]m/z 421.1977,found 421.1976.
Figure BDA0003069814030000354
1 H NMR(400MHz,CDCl 3 )δ7.79(s,1H),7.76(s,1H),7.49(d,J＝8.8Hz,2H),7.21(d,J＝8.0Hz,2H),4.41–4.24(m,3H),2.59–2.44(m,4H),1.90–1.87(m,2H),1.67–1.62(m,2H),1.50(s,9H)ppm. 13 C NMR(101MHz,CDCl 3 )δ153.52,147.64(q,J＝1.6Hz),135.92,131.55,126.67,125.03,121.77,121.50,120.53(q,J＝258.7Hz)79.56,53.10,51.97,51.11,34.52,34.07,28.69,28.51,28.15ppm.HRMS(EI-TOF)calcd for C 22 H 26 F 3 N 3 O 3 [M + ]m/z 437.1926,found 437.1928.
Figure BDA0003069814030000361
1 H NMR(400MHz,CDCl 3 )δ7.72(s,2H),7.41(d,J＝8.8Hz,2H),6.91(d,J＝8.7Hz,2H),4.39(tt,J＝6.8,3.9Hz,1H),3.82(s,3H),3.21(br,s,2H),2.49–2.36(m,4H),2.28(s,3H),1.96–1.92(m,2H),1.58(dd,J＝14.3,6.3Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ158.25,135.49,126.63,125.51,124.31,122.45,114.27,59.44,55.33,52.17,40.31,35.36,25.92ppm.HRMS(EI-TOF)calcd for C 18 H 23 N 3 O[M + ]m/z 297.1841,found 297.1845.
Figure BDA0003069814030000362
1 H NMR(400MHz,CDCl 3 )δ7.78(s,1H),7.77(s,1H),7.29(d,J＝9.8Hz,2H),7.24(t,J＝7.5Hz,1H),7.03(d,J＝7.2Hz,1H),4.39(tt,J＝6.8,3.6Hz,1H),3.20(br,s,2H),2.53–2.41(m,4H),2.37(s,3H),2.28(s,3H),1.95–1.91(m,2H),1.56(dd,J＝14.3,6.4Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ138.38,135.80,132.71,128.73,127.06,126.19,124.81,122.75,122.55,59.42,52.25,40.31,35.34,25.92,21.48ppm.HRMS(EI-TOF)calcd for C 18 H 23 N 3 [M + ]m/z 281.1892,found 281.1895.
Figure BDA0003069814030000363
1 H NMR(400MHz,CDCl 3 )δ7.77(s,1H),7.75(s,1H),7.40(d,J＝8.4Hz,2H),7.31(d,J＝8.3Hz,2H),4.40(tt,J＝6.8,3.7Hz,1H),3.20(br,s,2H),2.49–2.43(m,4H),2.27(s,3H),1.96–1.93(m,2H),1.55(dd,J＝14.1,6.0Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ135.71,131.80,131.35,128.92,126.63,124.90,121.59,59.36,52.42,40.35,35.50,26.03ppm.HRMS(EI-TOF)calcd for C 17 H 20 35 ClN 3 [M + ]m/z 301.1346,found 301.1348.calcd for C 17 H 20 37 ClN 3 [M + ]m/z 303.1316,found 303.1321.
Figure BDA0003069814030000364
1 H NMR(400MHz,CDCl 3 )δ7.85(s,1H),7.82(s,1H),7.61–7.56(m,4H),4.43(p,J＝5.2Hz,1H),3.23–3.21(m,2H),2.49–2.47(m,4H),2.28(s,3H),1.98–1.94(m,2H),1.56(dd,J＝14.9,6.0Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ136.43,135.97,128.07(q,J＝32.5Hz),125.76(q,J＝3.7Hz),125.41,125.36,124.28(q,J＝271.7Hz),121.36,59.34,52.54,40.31,35.50,26.02ppm.HRMS(EI-TOF)calcd for C 18 H 20 F 3 N 3 [M + ]m/z 335.1609,found 335.1612.
Figure BDA0003069814030000365
1 H NMR(400MHz,CDCl 3 )δ7.78(s,1H),7.75(s,1H),7.48(d,J＝8.5Hz,2H),7.20(d,J＝8.1Hz,2H),4.41(p,J＝5.0Hz,1H),3.21(br,s,2H),2.49–2.47(m,4H),2.28(s,3H),1.97–1.93(m,2H),1.57(dd,J＝14.5,6.2Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ147.55(q,J＝1.7Hz),135.76,131.73,126.61,124.99,121.46,120.50(d,J＝256.9Hz),59.40,52.36,40.26,35.38,25.92ppm.HRMS(EI-TOF)calcd for C 18 H 20 F 3 N 3 O[M + ]m/z 351.1558,found 351.1561.
Figure BDA0003069814030000371
1 H NMR(400MHz,CDCl 3 )δ8.66(d,J＝8.4Hz,1H),8.05(s,1H),7.99(s,1H),7.74(d,J＝8.4Hz,1H),7.54(d,J＝8.9Hz,1H),7.33(d,J＝8.9Hz,1H),4.64(p,J＝5.1Hz,1H),4.37–4.29(m,2H),2.70–2.55(m,4H),1.83–1.81(m,2H),1.68–1.62(m,2H),1.52(s,9H)ppm. 13 C NMR(101MHz,CDCl 3 )δ153.52,144.43,131.59,128.03(q,J＝32.2Hz),127.87,125.45(q,J＝3.9Hz),124.62(q,J＝272.1Hz),123.11,123.06,122.81,122.25(q,J＝3.2Hz),120.04,119.36,79.52,54.27,52.12,51.32,34.81,34.34,28.57,28.46,27.99ppm.HRMS(EI-TOF)calcd for C 24 H 26 F 3 N 3 O 2 [M + ]m/z 445.1977,found 445.1973.
Figure BDA0003069814030000372
1 H NMR(400MHz,CDCl 3 )δ8.43(s,1H),8.32(d,J＝8.5Hz,1H),8.20(s,1H),7.81–7.76(m,2H),7.53(d,J＝9.1Hz,1H),4.79(tt,J＝7.7,5.9Hz,1H),4.48–4.32(m,2H),2.74–2.63(m,2H),2.36–2.20(m,2H),2.04–1.93(m,4H),1.55(s,9H)ppm. 13 C NMR(101MHz,CDCl 3 )δ153.99,137.77,131.55,129.36,128.34,127.75,126.40(q,J＝32.4Hz),126.15(q,J＝4.4Hz),124.49(q,J＝271.6Hz),123.68,123.19(q,J＝4.2,3.7Hz),119.47,111.58,79.57,51.78,50.97,49.78,35.68,35.32,29.79,29.31,28.55ppm.HRMS(EI-TOF)calcd for C 24 H 26 F 3 N 3 O 2 [M + ]m/z 445.1977,found 445.1976.
Figure BDA0003069814030000373
1 H NMR(400MHz,CDCl 3 )δ8.48(s,1H),8.15(d,J＝8.3Hz,1H),8.10(s,1H),7.76–7.71(m,2H),7.62(d,J＝9.2Hz,1H),4.68(p,J＝5.6Hz,1H),4.42–4.33(m,2H),2.75–2.59(m,4H),1.92–1.89(m,2H),1.70–1.63(m,2H),1.52(s,9H)ppm. 13 C NMR(101MHz,CDCl 3 )δ153.59,147.12,129.81,129.58,127.56,126.84(q,J＝32.2Hz),126.07(q,J＝4.1Hz),124.50(q,J＝271.9Hz),123.80,122.64(q,J＝3.5Hz),122.09,119.31,117.77,79.67,54.50,51.95,51.13,35.16,34.77,29.07,28.52,28.45ppm.HRMS(EI-TOF)calcd for C 24 H 26 F 3 N 3 O 2 [M + ]m/z 445.1977,found 445.1971.
Figure BDA0003069814030000381
1 H NMR(400MHz,CDCl 3 )δ8.69(d,J＝8.4Hz,1H),8.07(s,1H),8.06(s,1H),7.75(dd,J＝8.3,1.2Hz,1H),7.59(d,J＝8.9Hz,1H),7.37(d,J＝8.9Hz,1H),4.71(tt,J＝6.6,3.1Hz,1H),3.25(s,2H),2.69–2.57(m,4H),2.30(s,3H),1.94–1.91(m,2H),1.64–1.59(m,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ144.46,131.54,127.96(q,J＝32.2Hz),127.90,125.47(q,J＝4.1Hz),124.62(q,J＝272.1Hz),123.06,122.99,122.73,122.24(q,J＝3.3Hz),120.10,119.23,59.49,53.54,40.15,35.73,25.82.HRMS(EI-TOF)calcd for C 20 H 20 F 3 N 3 [M + ]m/z 359.1609,found 359.1611.
Figure BDA0003069814030000382
1 H NMR(400MHz,CDCl 3 )δ8.38(s,1H),8.22(d,J＝8.1Hz,1H),7.89(d,J＝8.0Hz,1H),7.68(d,J＝9.1Hz,1H),7.61–7.57(m,1H),7.50(d,J＝9.1Hz,1H),7.47–7.43(m,1H),4.95(tt,J＝8.0,5.7Hz,1H),3.30–3.27(m,2H),2.65(dt,J＝14.6,7.6Hz,2H),2.31(s,3H),2.22(ddd,J＝14.3,5.6,1.1Hz,2H),2.11–2.04(m,2H),1.93–1.88(m,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ137.21,130.92,129.30,128.65,127.50,127.39,127.19,124.36,122.85,119.78,110.58,59.49,48.82,40.61,36.96,27.07ppm.HRMS(EI-TOF)calcd for C 19 H 21 N 3 [M + ]m/z 291.1735,found 291.1738.
Figure BDA0003069814030000383
1 H NMR(400MHz,CDCl 3 )δ8.34(s,1H),8.14(d,J＝8.6Hz,1H),7.86(d,J＝2.1Hz,1H),7.59(d,J＝9.1Hz,1H),7.53(dd,J＝8.6,2.0Hz,2H),4.94(tt,J＝8.0,5.8Hz,1H),3.30–3.27(m,2H),2.64(dt,J＝14.6,7.6Hz,2H),2.31(s,3H),2.19(ddd,J＝14.4,5.8,1.2Hz,2H),2.10–2.07(m,2H),1.88(dd,J＝13.9,6.3Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ137.15,130.85,130.19,129.79,127.67,127.57,126.32,125.76,124.36,119.46,111.73,59.43,48.98,40.65,37.04,27.13ppm.2D NOESY NMR(600MHz,CDCl 3 )showed a cross peak fromδ2.22,2.65,4.96 toδ7.56.HRMS(EI-TOF)calcd for C 19 H 20 35 ClN 3 [M + ]m/z 325.1346,found 325.1345.calcd for C 19 H 20 37 ClN 3 [M + ]m/z 327.1316,found 327.1322.
Figure BDA0003069814030000384
1 H NMR(400MHz,CDCl 3 )δ8.42(s,1H),8.31(d,J＝8.5Hz,1H),8.19(s,1H),7.80–7.75(m,2H),7.60(d,J＝9.1Hz,1H),5.01(tt,J＝8.1,5.0Hz,1H),3.40–3.37(m,2H),2.80(dt,J＝14.5,7.5Hz,2H),2.40(s,3H),2.29–2.24(m,2H),2.13–2.05(m,2H),2.03–1.98(m,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ137.80,131.37,129.34,128.32,127.63,126.31(q,J＝32.3Hz),126.12(q,J＝3.8Hz),124.49(q,J＝272.1Hz),123.65,123.11(q,J＝3.3Hz),119.42,111.87,59.80,48.70,40.30,36.51,26.60ppm.HRMS(EI-TOF)calcd for C 20 H 20 F 3 N 3 [M + ]m/z 359.1609,found 359.1604.
Figure BDA0003069814030000391
1 H NMR(400MHz,CDCl 3 )δ8.40(s,1H),8.05(d,J＝7.9Hz,1H),7.80(d,J＝7.9Hz,1H),7.66(d,J＝9.2Hz,1H),7.55(d,J＝9.2Hz,1H),7.51(t,J＝7.5Hz,1H),7.42(t,J＝7.5Hz,1H),4.69(tt,J＝7.0,3.8Hz,1H),3.25(br,s,2H),2.67–2.54(m,4H),2.28(s,3H),1.94–1.91(m,2H),1.57(dd,J＝14.5,6.5Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ146.75,130.20,128.83,127.69,127.59,126.55,124.85,123.16,121.27,118.17,117.88,59.46,53.51,40.32,35.91,26.15ppm.HRMS(EI-TOF)calcd for C 19 H 21 N 3 [M + ]m/z 291.1735,found 291.1737.
Figure BDA0003069814030000392
1 H NMR(400MHz,CDCl 3 )δ8.37(s,1H),7.97(d,J＝8.5Hz,1H),7.77(d,J＝2.1Hz,1H),7.68(d,J＝9.2Hz,1H),7.47–7.44(m,2H),4.70(p,J＝5.6Hz,1H),3.38–3.24(m,2H),2.62–2.59(m,4H),2.29(s,3H),1.97–1.94(m,2H),1.58(dd,J＝14.5,6.3Hz,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ146.59,131.29,130.24,127.89,126.83,126.57,125.90,124.57,121.33,119.16,117.75,59.44,53.67,40.33,36.05,26.25ppm.2D NOESY NMR(600MHz,CDCl 3 )showed a cross peak fromδ1.59,2.63,4.71toδ8.39.HRMS(EI-TOF)calcd for C 19 H 20 35 ClN 3 [M + ]m/z 325.1346,found 325.1342.calcd for C 19 H 20 37 ClN 3 [M + ]m/z 327.1316,found 327.1325.
Figure BDA0003069814030000393
1 H NMR(400MHz,CDCl 3 )δ8.48(s,1H),8.15(d,J＝8.4Hz,1H),8.09(s,1H),7.75(d,J＝9.2Hz,1H),7.72(dd,J＝8.4,1.3Hz,1H),7.60(d,J＝9.2Hz,1H),4.75(p,J＝5.6Hz,1H),3.29(p,J＝3.7Hz,2H),2.63(dd,J＝5.5,4.0Hz,4H),2.31(s,3H),1.99–1.96(m,2H),1.62–1.56(m,2H)ppm. 13 C NMR(101MHz,CDCl 3 )δ147.08,129.87(q,J＝0.6Hz),129.51,127.37,126.69(q,J＝32.2Hz),126.04(q,J＝4.2Hz),124.53(q,J＝271.8Hz),123.78,122.55(q,J＝3.4Hz),122.03,119.37,117.61,59.45,53.82,40.33,36.09,26.26ppm.HRMS(EI-TOF)calcd for C 20 H 20 F 3 N 3 [M + ]m/z 359.1609,found 359.1611.
example 37: nematicidal testing of the compounds of the invention.
Pine wood nematodes (Bursaphelenchus xylophilus) and Meloidogyne incognita (Meloidogyne incognita) selected by the present invention were purchased from the Huzhou modern agriculture center, a Chinese academy, and tested to determine the nematicidal activity of the compounds of the present invention.
The specific test operation process comprises the following steps:
an electronic analytical balance accurately weighs the positive control drug and the target compound respectively, and dissolves the positive control drug and the target compound by using dimethyl sulfoxide, and then the positive control drug and the target compound are diluted into a mother solution with a certain concentration by using an aqueous solution containing 0.2% triton, wherein the content of an organic solvent in the water is less than 1%, and the concentration of the mother solution is 2 times of the highest concentration required by a test. In actual test, a proper amount of mother liquor and an aqueous solution containing 0.2 percent of triton are respectively taken to be diluted to the required concentration for later use. The prepared drug solution was added to a 96-well plate at 50 μ L per well, and each drug was repeated twice. The nematode suspension (50. Mu.L, about 50 nematodes) was added to the drug by a continuous applicator, capped, and placed in an observation chamber at 22. + -. 1 ℃. Assuming that 0.2% triton aqueous solution per ml contains 4uL dimethyl sulfoxide as a CK control group, abamectin (5 ppm) and fluensulfone (5 ppm) as a positive control group, the number of nematode deaths at 24 hours, 48 hours and 72 hours is checked, and the average mortality of the nematodes in two repeated tests is calculated.
Corrected mortality = (treatment mortality-control mortality)/(1-control mortality) × 100%
TABLE 1 lethality (%), at 40ppm concentration, of the compounds of the invention against two nematodes
Figure BDA0003069814030000401
Figure BDA0003069814030000411
As can be seen from Table 1, some of the compounds had excellent nematicidal activity at a concentration of 40 ppm.
All documents referred to herein are incorporated by reference into this application as if each were individually incorporated by reference. Furthermore, it should be understood that various changes and modifications of the present invention can be made by those skilled in the art after reading the above teachings of the present invention, and these equivalents also fall within the scope of the present invention as defined by the appended claims.

Claims (11)

1. A compound having a structure selected from the group consisting of,
Figure FDA0004037706140000011
in the formula, R is C1-C4 alkyl;
ar is selected from: r is 1 Substituted benzene rings, unsubstituted naphthalene rings, unsubstituted 8-12 membered heteroaromatic bicyclic ring systems;
R 1 in an amount of 1,2 or 3, each R 1 Each independently selected from: C1-C6 alkyl, C1-C6 alkoxy, fluorine, chlorine, iodine, halogenated C1-C6 alkyl, halogenated C1-C6 alkoxy, nitro, phenyl or-OAr 1 (ii) a Wherein Ar is 1 Selected from the group consisting of: phenyl, 5-or 6-membered heteroaryl; wherein phenyl, 5-or 6-membered heteroaryl is optionally substituted with 1 or 2 substituents selected from the group consisting of: halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C1-C6 alkoxy.
2. The compound of claim 1, wherein R is methyl.
3. The compound of claim 1, wherein the compound has a structure selected from the group consisting of:
Figure FDA0004037706140000012
wherein Ar is R 1 A substituted benzene ring;
R 1 the number of each R is 1,2 or 3 1 Each independently selected from: C1-C6 alkyl, C1-C6 alkoxy, fluorine, chlorine, iodine, halogenated C1-C6 alkyl, halogenated C1-C6 alkoxy, nitro, phenyl or-OAr 1 (ii) a Wherein Ar 1 Selected from: phenyl, 5-or 6-membered heteroaryl; wherein phenyl, 5-or 6-membered heteroaryl is optionally substituted with 1 or 2 substituents selected from the group consisting of: halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C1-C6 alkoxy.
4. The compound of claim 1 or 3, wherein Ar is selected from the group consisting of: r 1 Substituted benzene rings, unsubstituted naphthalene rings, unsubstituted 8-to 10-membered heteroaromatic bicyclic ring systems having 1,2 or 3 substituents R 1 ；
In the formulae, each R 1 Each independently selected from: C1-C6 alkyl, C1-C4 alkoxy, fluorine, chlorine, halogenated C1-C4 alkyl, halogenated C1-C4 alkoxy, nitro, phenyl, -O-5-membered or 6-membered heteroaryl; wherein phenyl, 5-or 6-membered heteroaryl is optionally substituted with 1 or 2 substituents selected from the group consisting of: halogen, C1-C4 alkyl, halogenated C1-C4 alkyl, C1-C4 alkoxy.
5. A compound or an agriculturally pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of:
Figure FDA0004037706140000021
Figure FDA0004037706140000031
Figure FDA0004037706140000041
6. a pesticidal composition comprising a compound according to any one of claims 1 to 5 or an agriculturally pharmaceutically acceptable salt thereof; and an agriculturally acceptable carrier.
7. Use of a compound according to any one of claims 1 to 5 or an agriculturally pharmaceutically acceptable salt thereof or a pesticidal composition according to claim 6 for the preparation of a nematicidal or nematicidal agent.
8. Use according to claim 7, wherein the nematodes are selected from: pine wood nematode, root knot nematode, beet cyst nematode, potato gold thread nematode, soybean cyst nematode, sweet potato stem nematode, millet nematode and rice seed tip nematode.
9. A method of killing or preventing nematodes in or in the soil or environment surrounding a plant or plant part thereof, which comprises applying a compound as defined in any one of claims 1 to 5 or an agriculturally acceptable salt thereof or a pesticidal composition as defined in claim 6 to the soil or environment surrounding a plant or plant part which is or may be subject to pests.
10. The method according to claim 9, wherein the compound or the agriculturally pharmaceutically acceptable salt thereof or the pesticidal composition is applied at a concentration of 0.05 to 200ppm.
11. The method of claim 9, wherein the nematode is selected from the group consisting of: pine wood nematode, root knot nematode, beet cyst nematode, potato gold thread nematode, soybean cyst nematode, sweet potato stem nematode, millet nematode and rice seed tip nematode.
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