CN113200976A - 3-aryl azabicyclo derivatives, preparation thereof and nematicidal application thereof - Google Patents

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 a 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-Arylazabicyclic derivatives and their preparation and nematicidal applications

technical field

The present invention belongs to the field of pesticides. Specifically, the present invention relates to a 3-arylazabicyclic derivative and its preparation and nematicidal application.

technical background

Worldwide, plant-parasitic nematodes have developed into major pathogens of agroforestry plants, including cash crops such as potatoes, soybeans, tomato, and trees such as olive and pine. The annual loss of crop yield caused by plant-parasitic nematodes is about 12%-15%, and the global direct agricultural economic loss reaches 157 billion US dollars. Due to the endoparasitic nature of plant-parasitic nematodes, most of their life cycles are in the host plant. Complete, protected by host plant tissue and therefore difficult to control.

So far, more than 4100 species of plant-parasitic nematodes have been reported, among which the obligate biotrophic root-knot nematode (Meloidogyne spp.) is the most devastating. One-tenth of vegetable yields worldwide are affected by nematode infestation, of which 50% of these losses are caused by root-knot nematodes, which primarily infest the root elongation zone of plants with 2nd instar larvae (J2). At first, J2 releases cell wall lytic enzymes into the root epidermis of the host plant through the mouth needle, and then migrates through the cortex to the root apex region to parasitize the selected vascular tissue cells, and regulates the relationship between it and the host cells through the secretion of the root knot nematode nematode The complex parasitic relationship of nematodes, which in turn affects the development and gene expression of host cells, makes the host cells evolve into larger multinucleated cells, namely giant cells, which become the single nutritional supplier of nematodes. With the development of giant cells, adjacent vascular bundles and cortical cells proliferate and hypertrophy to form root nodes.

The pine wood nematode (Bursaphelenchus xylophilus) originally existed as an ecologically balanced species of pine trees in North America, and now it has developed into an invasive species of forest ecosystems in Japan, the Korean Peninsula and my country, and is further infecting Spain, Portugal, Europe and other places. In my country, more than 1 million hectares of pine trees die each year due to pine wood nematode damage. As a migratory endoparasitic nematode, pine wood nematode causes pine wilt disease, which seriously damages the forest ecosystem in Far East Asia. The pine wood nematode can be transmitted from dead pine trees by its vector insect, Monochamus spp. On healthy pine trees, unlike other nematodes of the same genus, pine wood nematodes have both phytophagy and bacteriophagic characteristics. The pine wood nematodes absorb nutrients from the parenchyma cells of the pine wood through the resin pipe, which in turn causes the pine tree to wither. When the pine tree dies, The pine wood nematode feeds on the fungus Botrytis cinerea that lives on pine trees

In 1881, carbon disulfide (CS ₂ ) was considered to be the first product with nematicidal activity, and in the early to mid-20th century, methyl bromide, chloropicrin (CP), DD mixtures (1,3-D and 1, 2-D, Shell Company in 1942), dibromochloropropane (DBCP, Dour Company in 1955), 1,2-dibromoethylene (EDB, Dow Company in 1946) and a series of halogenated hydrocarbon fumigants were introduced. For nematode control, in 1952, Stauffer Company launched Mylone for nematode control. In 1955, Stauffer Company developed products including Vapam and Sassen. Nematode agents can decompose in moist soil and release fumigant methyl isothiocyanate, hydrogen sulfide gas, formaldehyde and other components, so as to achieve the purpose of killing nematodes. Since the 1960s, organophosphorus and carbamate nematicides have gradually replaced fumigants, with Ethopropos, fosthiazate (1991), Oxamyl (1972), aldicarb ( Temik, 1962) as the representative of high-efficiency non-fumigant nematicides was launched. These nematicides mainly act on the acetylcholinesterase (AChE) of the nematode nervous system, resulting in the blockage of nerve conduction in the worm, resulting in the disorder of the nematode's physiological activity, and then die.

Due to environmental pressure, high toxicity, continuous improvement of nematode resistance due to long-term use, and some effects on non-target biological neurotoxicity, some nematicides have been gradually phased out from the market, and some have even been banned. There are few types of nematicides to choose from, and the development of novel nematicides is still indispensable.

SUMMARY OF THE INVENTION

The purpose of the present invention is to provide the preparation method and nematicidal application of a class of derivatives of 3-arylazabicyclo, especially the application in the field of plant parasitic nematodes, so as to protect plants.

The nematicidal compositions described herein comprise an effective amount of a compound or mixture of compounds having any of the formulae described herein, such as the compounds shown below.

The first aspect of the present invention provides the compound represented by the general formula I, or its optical isomers, cis-trans isomers, and agrochemically acceptable salts.

in,

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 alkoxy Carbonyl, C6-C10 aryl C1-C15 alkoxycarbonyl; the substituted refers to being substituted by 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, C6-C10 aryl;

X ₁ is CH=CH or does not exist, X ₂ is CH=CH or does not exist, and when X ₁ is CH=CH, X ₂ does not exist; when X ₂ is CH=CH, X ₁ does not exist;

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, the number is 0, 1, 2, 3 or 4, each R ¹ are each independently selected from: C1-C6 alkyl, C1-C6 alkoxy, halogen, halogenated C1-C6 alkyl, halogenated C1-C6 alkoxy, cyano, nitro, C6-C10 aryl base, 5-membered or 6-membered heteroaryl, or -OAr ¹ ; wherein Ar ¹ is a C6-C10 aryl, 5- or 6-membered heteroaryl or 8-12-membered heteroaromatic bicyclic ring system; wherein, C6- C10 aryl, 5- or 6-membered heteroaryl optionally substituted with 1, 2, 3 or 4 substituents selected from the group consisting of halogen, cyano, nitro, hydroxy, amino, C1-C6 alkyl , halogenated C1-C6 alkyl, C1-C6 alkoxy.

In another preferred example, R is a substituted or unsubstituted C1-C4 alkyl group or a substituted or unsubstituted C1-C4 alkoxycarbonyl group; the substituted refers to 1, 2 selected from the following group Or substituted by 3 substituents: halogen, cyano, nitro, hydroxyl, amino, C1-C4 alkyl, halogenated C1-C4 alkyl, C1-C4 alkoxy, carboxyl, phenyl.

In another preferred example, when D is S or O, B is C, A is N, and E is N or C(H), X ₁ and X ₂ do not exist.

In another preferred example, when D is S, B is C, A is N, E is N or C(H), and X ₁ and X ₂ do not exist.

In another preferred example, when D is O, B is C, A is N, E is N, and X ₁ and X ₂ do not exist.

In another preferred example, when D is N, B is C, A is S or N, and E is CH or O, X ₁ and X ₂ are absent.

In another preferred example, when D is N, B is C, A is S, E is CH, and X ₁ and X ₂ are absent.

In another preferred example, when D is N, B is C, A is N, E is O, and X ₁ and X ₂ are absent.

In another preferred example, when D is CH or N, B is N, A is CH or N, and E is C, X ₂ is CH=CH.

In another preferred example, when D is C, B is N, A is N, and E is CH, X ₁ is CH=CH.

In another preferred example, when D is CH or N, B is N, A is CH or N, and E is CH, X ₁ and X ₂ are absent.

In another preferred example, when D is N, B is N, A is CH, and E is CH, X ₁ and X ₂ do not exist.

In another preferred example, 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, and E is C, X is CH=CH.

In another preferred example, when D is CH, B is N, A is N, and E is CH, X ₁ and X ₂ are absent.

In another preferred embodiment, the compound has the following structure,

In the formula, Ar is as defined in claim 1, and optionally has 1, 2 or 3 substituents R ¹ ; the definitions of R and R ¹ are as described in claim 1 .

In another preferred example, Ar is a benzene ring, a naphthalene 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 is independently selected from: C1-C6 alkyl, C1-C4 alkoxy, fluorine, chlorine, bromine, halogenated C1-C4 alkyl, halogenated C1-C4 alkoxy, cyano base, nitro, phenyl, 5- or 6-membered heteroaryl, -O-phenyl, -O-5- or 6-membered heteroaryl; wherein, phenyl, 5- or 6-membered heteroaryl is optional is substituted with 1 or 2 substituents selected from the group consisting of halogen, cyano, nitro, hydroxy, amino, C1-C4 alkyl, halogenated C1-C4 alkyl, C1-C4 alkoxy.

In another preferred embodiment, the compound has the structure shown by one of 4aa-52ac.

In a second aspect of the present invention, there is provided a pesticide composition comprising the compound described in the first aspect or a pesticide acceptable salt thereof; and a pesticide acceptable carrier.

The third aspect of the present invention provides the use of the compound described in the first aspect or a pesticide acceptable salt thereof or the pesticide composition described in the second aspect, for killing nematodes or preventing nematodes; or for preparing a pesticide Nematodes or agents for preventing nematodes.

A fourth aspect of the present invention provides a method for killing or preventing nematodes, the method comprising applying the compound of the first aspect or a pesticidal acceptable salt thereof or the pesticide composition of the second aspect in or in the surrounding soil or environment of plants that are or may be infested.

The present invention provides a nematicidal or nematode prevention method, which comprises applying the azabicyclic derivative or a pesticidally acceptable salt thereof of the first aspect or the composition of the second aspect to a subject that suffers or is likely to suffer from Infested plant body or its surrounding soil or environment.

In another preferred embodiment, the application concentration of the azabicyclic derivative or its pesticide acceptable salt or the pesticide composition is 0.05-200 ppm; preferably, 0.1-100 ppm; more preferably, 0.5-50ppm.

In another preferred embodiment, the nematodes include, but are not limited to, pine wood nematode, root knot nematode, beet cyst nematode, potato golden nematode, soybean cyst nematode, sweet potato stem nematode, millet nematode, and rice grain nematode.

It should be understood that within the scope of the present invention, the above-mentioned technical features of the present invention and the technical features specifically described in the following (eg, the embodiments) can be combined with each other to form new or preferred technical solutions. Due to space limitations, it is not repeated here.

Detailed ways

After extensive and in-depth research, the inventors synthesized a class of azabicyclic derivatives with novel structures for the first time, and these compounds have excellent nematicidal activity. On this basis, the inventors completed the present invention.

basic definition

The term "C1-C15 alkyl" refers to a straight or branched chain alkyl group having 1-15 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, 1-butyl, 2-butyl , pentyl, hexyl, heptyl, octyl, nonyl, decyl or similar groups. A C1-C6 alkyl group may be preferred.

The term "C1-C15 alkoxy" refers to a straight or branched chain alkyl group having 1-15 carbon atoms, such as methoxy, ethoxy, n-propoxy, isopropoxy, 1-butoxy oxy, 2-butoxy, pentyloxy, hexyloxy, heptyloxy, octyloxy, nonyloxy, decyloxy or similar groups. A C1-C6 alkyl group may be preferred.

The term "C2-C6 alkenyl" refers to a straight-chain or branched alkenyl group having 2-6 carbon atoms, such as vinyl, n-propenyl, isopropenyl, 1-butenyl, 2-butenyl, Pentenyl, hexenyl or similar groups. A C2-C4 alkenyl group may be preferred.

The term "C2-C6alkynyl" refers to a straight or branched chain alkynyl group having 2 to 6 carbon atoms, such as ethynyl, n-propynyl, isopropynyl, 1-butynyl, 2-butynyl , pentynyl, hexynyl or similar groups. Preferably it is a C2-C4 alkynyl group.

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 "heterocycle" means that at least one of the atoms forming the heterocycle skeleton is not carbon, but nitrogen, oxygen or sulfur, and the heterocycle is a saturated or partially unsaturated non-aromatic heterocycle, preferably, the number of heteroatoms 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, such as phenyl, pyridyl, furanyl, 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, quinolyl, indolyl, benzothiophene, isoquinolinyl, benzothiophene, benzothiazole, benzopyrazole, benzimidazole, benzoxazole, benzo-[1,3]-dioxolane, etc.

The term "halogen" is fluorine, chlorine, bromine, iodine. The "halo" refers to fluoro, chloro, bromo and iodo.

The term "active substance of the present invention" or "active compound of the present invention" refers to a compound of the present invention or a pesticide acceptable salt thereof.

The agrochemically acceptable salts may include inorganic salts, organic acid salts, salts of basic amino acids or acidic amino acids. In the present invention, inorganic acid salts 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 (ie acetic acid), trifluoroacetic acid, fumaric acid, oxalic acid, maleic acid, citric acid, succinic acid, malic acid, methanesulfonic acid, benzenesulfonic acid, or p-toluene Sulfonic acid. Acidic amino acids include, for example: glycine, aspartic acid, or glutamic acid.

The compounds of the present invention are particularly effective against plant-parasitic nematodes.

Nematicidal combinations comprising active substances according to the invention.

The active substances of the present invention can be prepared into insecticidal compositions by conventional methods. These active compounds can be formulated into conventional formulations 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, which are liquid or liquefied gas or solid diluents or carriers, optionally with surfactants, ie emulsifiers and/or Dispersants and/or foam formers. For example, when water is used as an extender, organic solvents can also be used as auxiliaries.

When using liquid solvents as diluents or carriers, it is basically suitable, such as: aromatic hydrocarbons, such as xylene, toluene or alkylnaphthalene; chlorinated aromatic or chlorinated aliphatic hydrocarbons, such as chlorobenzene, vinyl chloride or methylene chloride; 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 unusual polar solvents such as dimethylformamide and dimethylsulfoxide, and water.

In terms of diluents or carriers of liquefied gases, it refers to liquids that will become gases at normal temperature and pressure, such as aerosol propellants, such as halogenated hydrocarbons and butane, propane, nitrogen and carbon dioxide.

The solid carrier may be ground natural minerals, such as kaolin, clay, talc, quartz, activated clay, montmorillonite, or diatomaceous earth, and ground synthetic minerals, such as highly dispersed silicic acid, alumina and silicates. Solid carriers for granules are ground and graded natural limestones such as calcite, marble, pumice, sepiolite and dolomite, as well as granules synthesized from inorganic and organic coarse powders, and organic materials such as sawdust, coconut shells, Particles of corn cobs and tobacco stems, etc.

Nonionic and anionic emulsifiers can be used as emulsifiers and/or foam formers. For example, polyoxyethylene-fatty acid esters, polyoxyethylene-fatty alcohol ethers, such as alkyl aryl polyglycol ethers, alkyl sulfonates, alkyl sulfates, aryl sulfonates and white protein hydrolysate. Dispersants include, for example, lignin sulfite waste liquor and methyl cellulose.

Binders such as carboxymethyl cellulose and natural and synthetic polymers in the form of powders, granules or emulsions, such as acacia, polyvinyl alcohol and polyvinyl acetate, can be used in the formulation.

Colorants such as inorganic dyes, such as iron oxide, cobalt oxide, and Prussian blue; organic dyes, such as organic dyes, such as chloro or metallocyanine dyes; and trace nutrients, such as iron, manganese, boron, copper, can be used , cobalt, aluminum and zinc salts, etc.

These formulations generally contain 0.001-99.99% by weight of the pesticidal composition, preferably 0.01-99.9% by weight, more preferably 0.05-90% by weight of the active compound of the invention. The concentration of active compound in the dosage forms prepared for use from commercial formulations can vary widely. The concentration of active compound in the dosage form used may be from 0.0000001 to 100% (g/v), preferably between 0.0001 and 1% (g/v).

The present invention will be further described below in conjunction with specific embodiments. It should be understood that these examples are only used to illustrate the present invention and not to limit the scope of the present invention. In the following examples, the experimental methods without specific conditions are usually in accordance with conventional conditions, or in accordance with the conditions suggested by the manufacturer. Percentages and parts are by weight unless otherwise indicated.

The invention provides a preparation method of azabicyclic derivatives, comprising the steps:

In an inert solvent (such as acetonitrile, methanol, isopropanol, ethanol, DMF, etc.), compound A1 and compound A2 are reacted to obtain compound A3

In the formula, R and Ar are as defined above.

or the method includes the steps:

(1) In an inert solvent (such as acetonitrile, methanol, isopropanol, ethanol, N,N-dimethylformamide, N,N-dimethylacetamide, water, toluene, dimethyl sulfoxide, etc.) , compound B1 and compound B2 are reacted to obtain compound B3;

(2) In an inert solvent (such as acetonitrile, methanol, isopropanol, ethanol, N,N-dimethylformamide, N,N-dimethylacetamide, water, toluene, dimethyl sulfoxide, etc.) , compound B4 and compound B5 are reacted to obtain compound B3.

In the formula, R and Ar are as defined above.

Or the method comprises the steps of: in an inert solvent (such as dichloromethane, ethyl acetate, tetrahydrofuran, N,N-diformamide, dioxane, dichloroethane, chloroform, toluene, xylene, dimethyl base sulfoxide, etc.), compound C1 and compound C2 are reacted to obtain compound C3;

In the formula, R and Ar are as defined above.

Or the method comprises the steps of: in an inert solvent (such as dichloromethane, ethyl acetate, tetrahydrofuran, N,N-diformamide, dioxane, dichloroethane, chloroform, toluene, xylene, dimethyl base sulfoxide, etc.), compound D1 and compound C2 are reacted to obtain compound D3;

In the formula, R and Ar are as defined above.

Or the method comprises the steps of: in an inert solvent (such as dichloromethane, ethyl acetate, tetrahydrofuran, N,N-diformamide, dioxane, dichloroethane, chloroform, toluene, xylene, dimethyl base sulfoxide, etc.), compound D1 and compound C2 are reacted with Lawson's reagent to obtain compound E3;

In the formula, R and Ar are as defined above.

Or the method comprises the steps of: in an inert solvent (such as dichloromethane, ethyl acetate, tetrahydrofuran, N,N-diformamide, dioxane, dichloroethane, chloroform, toluene, xylene, dimethyl base sulfoxide, etc.), compound F1 and compound F2 in alkaline (such as triethylamine, potassium carbonate, sodium carbonate, potassium hydroxide, sodium hydroxide, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydride, etc.) The reaction is carried out under conditions to obtain compound F3

In the formula, R and Ar are as defined above.

Or the method comprises the steps of: in an inert solvent (such as dichloromethane, ethyl acetate, tetrahydrofuran, N,N-diformamide, dioxane, dichloroethane, chloroform, toluene, xylene, dimethyl base sulfoxide, etc.), compound F1 and compound G2 in basic (such as triethylamine, potassium carbonate, sodium carbonate, potassium hydroxide, sodium hydroxide, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydride, etc.) The reaction is carried out under conditions to obtain compound G3

In the formula, R and Ar are as defined above.

Or the method comprises the steps of: in an inert solvent (such as dichloromethane, ethyl acetate, tetrahydrofuran, N,N-diformamide, dioxane, dichloroethane, chloroform, toluene, xylene, dimethyl base sulfoxide, etc.), compound F1 and compound H2 in basic (such as triethylamine, potassium carbonate, sodium carbonate, potassium hydroxide, sodium hydroxide, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydride, etc.) The reaction is carried out under conditions to obtain compounds H3 and H4

In the formula, R and R ¹ are as defined above.

Or the method comprises the steps of: in an inert solvent (such as dichloromethane, ethyl acetate, tetrahydrofuran, N,N-diformamide, dioxane, dichloroethane, chloroform, toluene, xylene, dimethyl base sulfoxide, etc.), compound F1 and compound I2 in basic (such as triethylamine, potassium carbonate, sodium carbonate, potassium hydroxide, sodium hydroxide, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydride, etc.) The reaction is carried out under conditions to obtain compounds I3 and I4;

In the formula, R and R ¹ are as defined above.

The preparation methods of the compounds of the present invention are described in more detail below, but these specific methods do not constitute any limitation of the present invention. The compounds of the present invention can also be conveniently prepared by optionally combining various synthetic methods described in this specification or known in the art, and such combinations can be easily carried out by those skilled in the art to which the present invention belongs.

Preparation of intermediates:

In the formula, Ar is defined as before.

Example 1: Preparation of Intermediate 2.

In a 500 mL round-bottomed flask, 40.0 mmol of Tropinone 1, 60.0 mmol of tert-butanol, and 300 mL of tetrahydrofuran were successively added, the reaction solution was placed in an ice-water bath, stirred and cooled to 0 °C, and then 80 mmol of potassium tert-butoxide was added at one time, And keep stirring at 0 °C for 10 min, dissolve 60.0 mmol of p-toluenesulfonylmethyl isonitrile in 60 mL of tetrahydrofuran and slowly add it dropwise to the reaction solution. The reaction was carried out at room temperature for 6 h. After the reaction was completed, the solvent was removed by rotary evaporation, 125 mL of deionized water was added, extracted with dichloromethane (3×50 mL), the organic phases were combined, and the solvent was removed under reduced pressure to obtain a crude product, which was separated by column chromatography to obtain 5.4 g Colorless oil, 89% yield; ¹ H NMR (400 MHz, CDCl ₃ ) δ 3.20-3.18 (m, 2H), 2.73 (tt, J=12.1, 5.6 Hz, 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 CNMR (101 MHz, CDCl ₃ ) δ 122.31, 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: Preparation of Intermediate 3.

Into a 350 mL reaction flask, 20.0 mmol of compound 2, 150 mL of pyridine, and 30.0 mmol of a 20% ammonium sulfide aqueous solution were sequentially added, and the reaction solution was slowly heated to 55 °C for 48 h. After the reaction was completed, the solvent was removed by rotary evaporation, and the reaction residue was dissolved in 100 mL of ice. The pH was adjusted to 8-9 with saturated aqueous sodium carbonate solution in water, filtered, and the filter cake was dried and used directly for the next reaction. Light yellow solid 2.1 g, yield 58%; ¹ H NMR (400MHz, DMSO-d ₆ )δ 9.28(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: Preparation of target product 4.

In a 10 mL round-bottomed flask, 1 mmol of intermediate 3 and 1.1 mmol of α-bromoaryl ethyl ketone were added successively, 5 mL of absolute ethanol was added, and the reaction solution was heated to reflux for 3 h. After the reaction was completed, the solvent was removed by rotary evaporation, and the crude The product was purified by flash chromatography to give the title compound 4.

In the formula, Ar is defined as before.

Example 4: Preparation of Intermediate 5.

To a 100 mL round-bottomed flask, 10 mmol of compound 3, 15 mmol of sodium acetate, 50 mL of acetic acid, and 13 mmol of a 40% chloroacetaldehyde aqueous solution were sequentially added, stirred and slowly heated to 80 °C for 12 h. After the reaction was completed, the solvent was removed under reduced pressure, and 30 mL of the reaction residue was added. Deionized water was used to adjust the pH to 8-9 with saturated aqueous sodium carbonate solution, extracted with dichloromethane (3×30 mL), the organic phases were combined, and the solvent was removed under reduced pressure to obtain a crude product, which was separated by column chromatography to obtain 1.30 g of brown oil in a yield of 63 %. ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.56 (d, J=3.3 Hz, 1H), 7.14 (d, J=3.3 Hz, 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, 6.1 Hz, 2H) ppm. ¹³ C NMR (101 MHz, CDCl ₃ ) δ 173.98, 141.92, 118.21, 61.74, 39.05, 36.64, 32.77, 25.62 ppm. MS (GC-MS): C ₉ H ₁₆ N ₂ S[M] ⁺ m/z 208.1.

Example 5: Preparation of target product 6.

2mmol silver carbonate, 0.05mmol [1,1'-bis(diphenylphosphine)ferrocene]dichloropalladium dichloromethane complex, 0.1mmol triphenylphosphine, 1.2mmol aryl iodide were added in sequence In a 25mL three-port glass reactor, add 1mmol of compound 5 and 10mL of deionized water, place the reactor in a microwave synthesizer, insert an ultrasonic probe, adjust the height of the probe so that it is immersed 2-3mm below the liquid surface, and turn on the condensation Water, adjust the microwave power to 60W, the ultrasonic power to 75W, and react for 1.5 hours. After the reaction of the raw materials is complete, the reaction solution is cooled to room temperature, and the reaction solution is transferred to a 125mL separatory funnel, and extracted with dichloromethane (3×30mL). After filtering with algae, the extracts were combined, the solvent was removed by rotary evaporation, and the target compound 6 was obtained by column chromatography.

In the formula, Ar is defined as before.

Example 6: Preparation of Intermediate 8.

Using compound 7 as the reaction raw material, the specific implementation method is the same as the preparation of the above-mentioned intermediate 2. ¹ H NMR (400 MHz, CDCl ₃ ) δ 4.28-4.23 (m, 2H), 2.98 (tt, J=11.9, 5.5 Hz, 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.

To a 100 mL round-bottomed flask, 10 mmol of intermediate 8, 15 mmol of hydroxylamine hydrochloride, 20.0 mmol of sodium bicarbonate, 40 mL of ethanol, and 8 mL of deionized water were sequentially added. The reaction solution was stirred at room temperature for 1 h, and then the reaction solution was heated to reflux for 8 h. After the reaction, the solvent was removed by rotary evaporation, the reaction residue was dissolved in 20 mL of deionized water, extracted with ethyl acetate (3×20 mL), the extracts were combined, and the solvent was removed under reduced pressure to obtain a crude product that was directly used in the next reaction.

Example 8: Preparation of Intermediate 10.

Into a 50mL round-bottomed flask, 2mmol of compound 9, 3mmol of arylformic acid, 10mmol of triethylamine, 5.0mmol of 1-propyl cyclophosphoric anhydride, 20mL of ethyl acetate were successively added, and the reaction solution was replaced with nitrogen three times and refluxed under nitrogen atmosphere. After the reaction was completed, the ethyl acetate was removed by rotary evaporation, the reaction residue was dissolved in 20 mL of deionized water, and the pH was adjusted to 8-9 with saturated aqueous sodium carbonate solution, extracted with ethyl acetate (20 mL × 3), the extracts were combined, and the crude The product was isolated by column chromatography to give intermediate 10.

Example 9: Preparation of target product 11.

To a 25 mL round-bottomed flask, 1 mmol of compound 10, 10 mL of dichloromethane and 2 mL of trifluoroacetic acid were sequentially added, and the reaction was stirred at room temperature for 5 h. After the reaction was completed, the solvent was removed by rotary evaporation. Slowly adjust the pH to 8-9, extract with dichloromethane (20 mL×3), combine the extracts, remove the solvent by rotary evaporation, add 5 mmol 37% aqueous formaldehyde solution, 10 mmol acetic acid, 5 mmol zinc scraps, and 10 mL of solvent deionized water in sequence, The reaction solution was placed in an oil bath at 100 °C for 12 h. After the reaction, saturated aqueous Na ₂ CO ₃ solution was slowly added to adjust the pH of the reaction solution to 8-9, extracted with dichloromethane (20 mL×4), the extracts were combined and removed by rotary evaporation. After removing the solvent, the target product 11 was obtained by column chromatography.

In the formula, Ar is defined as before.

Example 10: Preparation of Intermediate 13.

To a 250mL round-bottomed flask, 40mmol of desmethyltropinone hydrochloride 12, 45mmol of benzyl bromide, and 150ml of acetonitrile were sequentially added, stirred at room temperature, 100mmol of potassium carbonate was added, and then the reaction solution was heated to reflux for 8h, and the reaction ended. , the reaction solution was cooled to room temperature, filtered with suction, the filter cake was washed with ethyl acetate (10 mL×3), the filtrate was subjected to rotary evaporation to remove the solvent, and the crude product was separated by column chromatography to obtain 7.5 g of colorless oily intermediate 13, 87% Yield, ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.40 (d, J=7.4 Hz, 2H), 7.32 (t, J=7.4 Hz, 2H), 7.24 (t, J=7.3 Hz, 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, 6.7 Hz, 2H) ppm. ¹³ C NMR (101 MHz, CDCl ₃ ) δ 210.09, 139.39, 128.44, 128.38, 127.12, 58.59, 55.13, 48.24, 27.86 ppm.

Example 11: Preparation of Intermediate 14.

Using intermediate 13 as the reaction raw material, the specific implementation steps are the same as the preparation of intermediate 2 above. 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.

Into a 250mL round-bottomed flask, 20mmol of intermediate 14, 100mL of deionized water, and 20mL of concentrated hydrochloric acid were added in sequence, and the reaction solution was heated to reflux for 48h. The reaction was completed. After the reaction solution was cooled to room temperature, the hydrochloric acid and water were removed under reduced pressure to obtain a brown sticky liquid The thick crude product was directly used in the next reaction.

Example 13: Preparation of Intermediate 16.

Transfer all of the above-obtained intermediate 15 to a 250 mL round-bottomed flask, add 4 mmol of p-toluenesulfonic acid, 100 mL of absolute ethanol, and heat to reflux for 8 h. After the reaction is completed, the reaction solution is cooled to room temperature, and the ethanol is removed by rotary evaporation. The product was isolated by column chromatography to give 4.8 g of oil in 88% yield. ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.39 (d, J=7.6 Hz, 2H), 7.30 (t, J=7.4 Hz, 2H), 7.22 (t, J=7.2 Hz, 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=12.1 Hz, 2H), 1.65-1.56 (m, 4H), 1.23 (t, J=7.1 Hz, 3H) ppm. ¹³ C NMR (101 MHz, CDCl ₃ ) δ 175.75, 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.

30mmol of intermediate 16, 45mmol of 80% hydrazine hydrate, and 80mL of absolute ethanol were successively added to a 250mL round-bottomed flask, the reaction solution was heated to reflux, and the reaction was stirred for 48h. After the reaction was completed, the reaction solution was cooled to room temperature, and the ethanol was removed by rotary evaporation. A white solid crude product was obtained, the crude product was washed with cold water three times, and filtered to obtain a white solid, which could be directly used in the next reaction after drying. White solid 4.6 g, 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, 5.8 Hz, 2H), 1.37–1.32 (m, 2H) ppm. ¹³ C NMR (101 MHz, 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.

To a 50 mL round-bottomed flask, 2 mmol of compound 17, 3 mmol of aryl formic acid, 5 mmol of triethylamine, 5 mmol of 1-propyl cyclic phosphoric anhydride, and 20 mL of ethyl acetate were sequentially added, the reaction solution was replaced with nitrogen three times, and refluxed for 8 h under nitrogen atmosphere. After the reaction was completed, it was cooled to room temperature, ethyl acetate was removed by rotary evaporation, the reaction residue was dissolved in 20 mL of deionized water, and the pH was adjusted to 8-9 with saturated aqueous sodium carbonate solution, extracted with ethyl acetate (20 mL×3), and the extracts were combined , the solvent was removed by rotary evaporation, and the target product was obtained by column chromatography.

Example 16: Preparation of Intermediate 19.

Into a 25mL round-bottomed flask, 1mmol of compound 18, 10mL of anhydrous acetonitrile, and 2mL of phosphorus oxychloride were sequentially added, and the reaction solution was heated to reflux and stirred for 12h. After the reaction was completed, it was cooled to room temperature, and 5mL of deionized water was slowly added, and continued After stirring for 10 min, the reaction solution was slowly added dropwise with saturated aqueous sodium carbonate solution to adjust the pH of the reaction solution to 8-9, the acetonitrile was removed by rotary evaporation, the reaction residue was dissolved in 10 mL of deionized water, extracted with dichloromethane (3×20 mL), and the combined The extraction liquid, the solvent was removed by rotary evaporation, and the target product was obtained by column chromatography.

Example 17: Preparation of target compound 20.

0.5mmol of intermediate 19, 10mL of anhydrous methanol, 100.0mg of 10% palladium on carbon, 5.0mmol of ammonium formate were successively added to a 25mL round-bottomed flask, and the reaction was stirred at room temperature overnight. After the reaction was completed, the reaction solution was filtered through diatomaceous earth. , the filtrate was evaporated to remove the solvent, dissolved in 10 mL of deionized water, and extracted with dichloromethane (10 mL × 3), the extracts were combined and the solvent was removed, followed by adding 2.5 mmol zinc filings, 2.5 mmol 37% formaldehyde solution, 5 mmol Acetic acid, 10 mL of deionized water, the reaction solution was placed at 100 ° C for 12 h, after the reaction was completed, after the reaction solution was cooled to room temperature, the pH of the reaction solution was adjusted to 8-9 with saturated sodium carbonate solution, and the reaction solution was extracted with dichloromethane ( 20 mL×3), the extracts were combined, the solvent was removed under reduced pressure, and the target compound 20 was obtained by column chromatography.

Example 18: Preparation of Intermediate 21.

Into a 50mL round-bottomed flask, successively added 2mmol of Intermediate 18, 20mL of anhydrous methanol, 400.0mg of 10% palladium on carbon, and 5mmol of ammonium formate, and the reaction was stirred overnight at room temperature. After the solvent was removed by rotary evaporation, it was dissolved in 20 mL of deionized water and extracted with dichloromethane (20 mL×3). After combining the extracts and removing the solvent, the crude product was directly used in the next reaction without column chromatography.

Example 19: Preparation of Intermediate 22.

Into a 50mL round-bottomed flask, 1.5mmol of intermediate 21, 20mL of toluene, and 4mmol of Lawson's reagent were sequentially added, and the reaction solution was heated to reflux for 12h. After the reaction of the raw materials was completed, the reaction solution was cooled to room temperature, and 20mL of deionized water was added, and acetic acid was added. Ethyl ester extraction (20 mL×3), after combining the extracts and removing the solvent, the crude product was separated by column chromatography and used for the next reaction.

Example 20: Preparation of target compound 23.

Into a 25mL round-bottomed flask, 0.5mmol of intermediate 22, 2.5mmol of zinc scraps, 2.5mmol of 37% aqueous formaldehyde solution, 5mmol of acetic acid, and 10mL of deionized water were sequentially added, and the reaction solution was placed at 100°C for 12h. The solution was cooled to room temperature, the pH of the reaction solution was adjusted to 8-9 with saturated sodium carbonate solution, the reaction solution was extracted with dichloromethane (20 mL×3), the extracts were combined, the solvent was removed under reduced pressure, and the target compound was obtained by column chromatography.

In the formula, R is defined as before.

Example 21: Preparation of Intermediate 25.

Into a 250mL round-bottomed flask, 150mL of dichloromethane and 40mmol of compound 24 were successively added, then 60mmol of imidazole and 52mmol of triphenylphosphine were successively added, stirred and cooled to 0°C, then 48mmol of iodine was added at one time, and the reaction was continued to stir at 0°C for 30min. , then transferred to room temperature and reacted overnight. After the reaction was completed, suction filtration was used to remove insoluble matter, the filter cake was washed with dichloromethane (20 mL×3), the filtrates were combined, the solvent was removed under reduced pressure, 30 mL of deionized water was added to the reaction residue, and Saturated aqueous sodium carbonate solution was adjusted to pH 8-9, and extracted with dichloromethane (50 mL×3), the extract was removed the solvent under reduced pressure, and the crude product was separated by column chromatography to obtain the target product.

In the formula, Ar is defined as before.

Example 22: Preparation of Intermediate 27.

To a 100 mL round-bottomed flask, 5 mmol of compound 26, 7.5 mmol of N,N-dimethylformamide dimethyl acetal, and 20 mL of absolute ethanol were added in sequence, and the reaction was heated to reflux for 48 h. After the reaction was completed, the reaction solution was cooled to room temperature. The ethanol was removed under reduced pressure, the reaction residue was dissolved in 50 mL of ethyl acetate, and washed with saturated brine (20 mL×3).

Example 23: Preparation of Intermediate 28.

To a 50 mL round-bottomed flask, 3 mmol of intermediate 27, 4.5 mmol of hydrazine hydrochloride, 0.6 mmol of p-toluenesulfonic acid, and 20 mL of absolute ethanol were sequentially added, and heated to reflux for 6-8 h. After the reaction was completed, the reaction solution was cooled to room temperature and reduced in pressure. Ethanol was removed, the reaction residue was dissolved in 30 mL of deionized water, extracted with ethyl acetate (30 mL×3), the extracts were combined, and the crude product was separated by column chromatography to obtain the target product.

Example 24: Preparation of Intermediate 29.

Into a 25mL round-bottomed flask, 2mmol of intermediate 28, 10mL of anhydrous N,N-dimethylformamide, and 5mmol of sodium hydride were successively added, and the reaction solution was reacted at room temperature for 10min under nitrogen atmosphere, and then 3mmol of intermediate 25 was added, and the reaction was carried out. The solution was slowly heated to 70 °C and continued to react for 12 h. After the reaction was completed, the reaction solution was cooled to room temperature, and 1.0 mL of deionized water was slowly added dropwise to quench the remaining sodium hydride. The reaction solution was transferred to a separatory funnel, and deionized water (20 mL) was added. , and extracted with ethyl acetate (20 mL×3), the extracts were combined, the solvent was removed by rotary evaporation, and the target product was obtained by column chromatography.

Example 25: Preparation of target compound 30.

Taking the intermediate 29 as the reaction raw material, when the R group is benzyl or benzyloxycarbonyl, the specific implementation steps are the same as the preparation method of the above-mentioned target product 20; when the R group is tert-butoxycarbonyl, the specific implementation steps are the same as the above-mentioned target. Process for the preparation of product 11.

In the formula, R and Ar are as defined above.

Example 26: Preparation of Intermediate 32.

It is obtained by reacting 4-bromo-1-H-pyrazole 31 and intermediate 25 under alkaline conditions, and the specific implementation method is the same as the preparation method of intermediate 29 above.

Example 27: Preparation of Intermediate 33.

Into a 25mL round-bottomed flask were sequentially added 2mmol of intermediate 32, 3mmol of arylboronic acid, 4mmol of potassium carbonate, 0.1mmol of tetrakistriphenylphosphine palladium, followed by 10mL of toluene, 1mL of absolute ethanol and 1mL of deionized water, and the reaction solution was placed The reaction was refluxed at 90 °C for 16 h. After the reaction was completed, the reaction solution was cooled to room temperature, and the solvent was removed under reduced pressure. The reaction residue was dissolved in 20 mL of deionized water, extracted with ethyl acetate (20 mL × 3), the extracts were combined, and the crude product was filtered through a column. The target product was obtained by chromatographic separation.

Example 28: Preparation of target compound 34.

The intermediate 33 is the reaction raw material. When the R group is a tert-butoxycarbonyl group, the specific implementation steps are the same as the above-mentioned preparation method of the target product 11.

In the formula, R and R ¹ are as defined above.

Example 29: Preparation of Intermediate 36.

Into a 25mL round-bottomed flask, 20mmol of N-methyl-5-hydroxypyrazole 35 and 6.0mL of anhydrous N,N-dimethylformamide were successively added, and the reaction solution was placed in an ice-water bath with stirring and cooled to 0°C. Then, 6.0 mL of phosphorus tribromide was slowly added dropwise to the reaction solution. After the dropwise addition, the reaction was kept at 0 °C for 10 min, and then the reaction temperature was slowly increased to 80 °C and the reaction was continued for 8 h. After the reaction, the reaction solution was cooled to room temperature. , 20 mL of deionized water was slowly added to the reaction solution until the viscous reaction solution was completely dissolved, and the pH was slowly adjusted to 8-9 with saturated aqueous sodium carbonate solution, the reaction solution was extracted with ethyl acetate (30 mL×3), and saturated brine was used. The extract was washed (20 mL×3), the solvent was removed by rotary evaporation, and the crude product was separated by column chromatography to obtain the 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 1-methyl-1H-pyrazole-5-carbaldehyde 40 and 20mL reaction solvent N,N-dimethylformamide were successively added to the 100mL round-bottomed flask, and stirred at room temperature until the raw materials were dissolved, then 11mmol N - Bromosuccinimide was dissolved in 10 mL of N,N-dimethylformamide and slowly added dropwise to the reaction solution. The reaction solution was placed at room temperature and continued to stir for 18 h. After the reaction, 10 mL of 20% sodium hydroxide was added. The aqueous solution was stirred for 10 min, then 50 mL of deionized water was added to the reaction solution, extracted with ethyl acetate (30 mL × 3), the extracts were combined and washed with saturated brine (20 mL × 3), the solvent was removed by rotary evaporation, and the crude The product was separated by 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.

Intermediate 36 or intermediate 41 are used as reaction raw materials, respectively, and the specific implementation steps are the same as the above-mentioned synthesis method of intermediate 33.

Example 32: Preparation of Intermediate 38 and Intermediate 43.

To a 20 mL microwave reaction tube equipped with a magnetic stirrer, 0.5 mmol of intermediate 37 or intermediate 42, 1.1 mmol of p-toluenesulfonyl hydrazide, and 6 mL of n-butanol were sequentially added, and the microwave tube was sealed and placed in a microwave synthesizer for reaction at 120 °C for 5 min. After the reaction, the solvent was removed under reduced pressure, and the intermediate 38 or the intermediate 43 was obtained by column chromatography.

Example 33: Preparation of Intermediate 39 and Intermediate 44.

To a 20 mL microwave reaction tube equipped with a magnetic stirring bar, 1 mmol of Intermediate 38 or Intermediate 43 was added in turn, then 15.0 g of pyridine hydrochloride was quickly added and the microwave tube was quickly capped. The microwave tube was placed in the microwave synthesizer and kept The reaction was carried out at 200 °C for 5 h. After the reaction, the reactant was dissolved in 30 mL of deionized water, extracted with ethyl acetate (20 mL×4), the extracts were combined, the solvent was removed by rotary evaporation, and the intermediate 39 or intermediate was separated by column chromatography. 44.

Example 34: Preparation of Intermediate 45 and Intermediate 47.

Intermediate 45 and intermediate 47 are obtained by reacting intermediate 39 and intermediate 25 under alkaline conditions, and the specific implementation steps are the same as the above-mentioned preparation method of intermediate 29.

Example 35: Preparation of Intermediate 49 and Intermediate 51.

Intermediate 44 and intermediate 25 are reacted under alkaline conditions to obtain intermediate 49 and intermediate 51. The specific implementation steps are the same as the above-mentioned preparation method of intermediate 29.

Example 36: Preparation of target products 46, 48, 50, 52.

Respectively, the intermediates 45, 47, 49, and 51 were reacted with the raw materials. When the R group is tert-butoxycarbonyl, the specific implementation steps are the same as the above-mentioned preparation method of intermediate 11.

According to the methods shown in the above Examples 1 to 36, the following compounds were prepared using different starting materials. The characterization data of hydrogen nuclear magnetic resonance ( ¹ H NMR), carbon spectrum ( ¹³ C NMR) and high-resolution mass spectrometry (HRMS) are as follows:

¹ H NMR (400 MHz, CD ₃ OD) δ 7.91 (d, J=7.1 Hz, 2H), 7.67 (s, 1H), 7.41 (t, J=7.5 Hz, 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 (101 MHz, CD ₃ OD) δ 174.75, 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.

¹ H NMR (400 MHz, CD ₃ OD) δ 7.85 (d, J=7.8 Hz, 2H), 7.47 (s, 1H), 7.29 (d, J=7.9 Hz, 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, _CD3OD ) _{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 _C18H22N2S [M ⁺ ]m /z 298.1504; found, 298.1502.

¹ H NMR (400 MHz, CD ₃ OD) δ 7.71 (d, J=8.8 Hz, 2H), 7.39 (s, 1H), 6.85 (d, J=8.8 Hz, 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) δ 175.06, 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.

¹ H NMR (400 MHz, CD ₃ OD) δ 7.96–7.88 (m, 2H), 7.63 (s, 1H), 7.13 (t, J=8.7 Hz, 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=8.1 Hz, 2H). ¹³ CNMR (101 MHz, CD ₃ OD) δ 175.05, 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.

¹ H NMR (400 MHz, CD ₃ OD) δ 7.89 (d, J=8.6 Hz, 2H), 7.71 (s, 1H), 7.39 (d, J=8.6 Hz, 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 (101 MHz, CD ₃ OD) δ 174.66, 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/z318.0957;found,318.0959 ;calcd for C ₁₇ H ₁₉ ³⁷ ClN ₂ S[M ⁺ ]m/z 320.0928; found, 320.0927.

¹ H NMR (400 MHz, CD ₃ OD) δ 7.82 (d, J=8.6 Hz, 2H), 7.72 (s, 1H), 7.54 (d, J=8.6 Hz, 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) δ 174.94, 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/z362.0452;found,362.0449 ;calcd for C ₁₇ H ₁₉ ⁸¹ BrN ₂ S[M ⁺ ]m/z 364.0432; found, 364.0428.

¹ H NMR (400 MHz, CD ₃ OD) δ 8.27 (d, J=9.0 Hz, 2H), 8.10 (d, J=9.0 Hz, 2H), 7.84 (s, 1H), 3.80 (s, 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 forC ₁₇ H ₁₉ N ₃ O ₂ S[ M ⁺ ]m/z 329.1198; found, 329.1197.

¹ H NMR (400 MHz, CD ₃ OD) δ 8.11 (d, J=8.2 Hz, 2H), 7.92 (s, 1H), 7.69 (d, J=8.4 Hz, 2H), 3.91 (s, 2H), ¹³ C NMR (101MHz, CD ₃ OD) δ 174.38, 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.

¹ H NMR (400 MHz, CD ₃ OD) δ 7.94 (s, 1H), 7.73–7.54 (m, 2H), 7.39 (d, J=8.4 Hz, 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 CNMR (101 MHz, CD ₃ OD) δ 174.64, 153.74, 135.93, 133.93 ^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.

¹ H NMR (400MHz, CD ₃ OD) δ 7.78-7.74 (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 (101 MHz, CD ₃ OD) δ 174.77, 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/z352.0568; 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.

¹ H NMR (400MHz, CD ₃ OD) δ 7.60(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, _CD3OD )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 _C15H18N2OS [M ⁺ ]m/ _z274 .1140; found, 274.1141.

¹ H NMR (400 MHz, CD ₃ OD) δ 8.68 (d, J=6.3 Hz, 2H), 7.89 (d, J=6.3 Hz, 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/z285 .1300; found, 285.1299.

¹ H NMR (400 MHz, CD ₃ OD) δ 7.73 (s, 1H), 7.45 (d, J=8.7 Hz, 2H), 6.92 (d, J=8.8 Hz, 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, 6.0 Hz, 2H) ppm. ¹³ C NMR (101 MHz, CD ₃ OD) δ 175.40, 161.35, 139.81, 137.08, 128.91, 125.04, 115.68, 62.48, 55.92, 40.26, 38.74, 34.148, 268. ppm.HRMS(EI-TOF)calcd for C ₁₈ H ₂₂ N ₂ OS[M ⁺ ]m/z 314.1453, found314.1457.

¹ H NMR (400 MHz, CD ₃ OD) δ 7.58 (s, 1H), 7.32 (d, J=7.4 Hz, 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.

¹ H NMR (400 MHz, CD ₃ OD) δ 7.74 (s, 1H), 7.42 (d, J=7.3 Hz, 2H), 7.25 (t, J=7.5 Hz, 2H), 7.18 (t, J=7.3 Hz, 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, 2.8 Hz, 2H), 1.63 (dd, J=14.2, 6.1 Hz, 2H) ppm. ¹³ C NMR (101 MHz, CD ₃ OD) δ 176.21, 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,found284.1348.

¹ H NMR (400MHz, CD ₃ OD) δ 7.87(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 (101 MHz, CD ₃ OD) δ 176.93, 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/z318.0957,found 318.0956. calcd for C ₁₇ H ₁₉ ³⁷ ClN ₂ S[M ⁺ ]m/z 320..0928,found320..0928.

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.78 (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 2 S 19} ⁷⁹ 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.

¹ H NMR (400 MHz, CDCl ₃ ) δ 8.18–8.15 (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, 6.1 Hz, 2H) ppm. ¹³ C NMR (101 MHz, CDCl ₃ ) δ 175.07, 146.05, 138.80, 136.88, 135.20, 125.93, 123.46, 60.79, 38.37, 35.88, 32.55, 24.68 ppm. HRMS (EI-TOF )calcd for C ₁₇ H ₁₉ N ₃ O ₂ S[M ⁺ ]m/z 329.1198, found 329.1197.

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 (100 MHz, CDCl ₃ ) δ 173.71, 137.72, 135.95, 133.97, 128.75 (q, J=32.7 Hz), 125.70, 124.98 (q, J=3.7 Hz), 122.97 (q, J=272.1 Hz) ,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/z352.1221,found 352.1222.

¹ H NMR (400MHz, CD ₃ OD) δ 7.65 (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=8.2 Hz),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)calcdfor C ₁₇ H ₁₉ FN ₂ S[M ⁺ ]m/z 302.1253, found 302.1252.

¹ H NMR (400 MHz, CD ₃ OD) δ 8.28 (s, 1H), 8.09 (dd, J=8.2, 2.0 Hz, 1H), 7.85 (s, 1H), 7.76 (d, J=7.8 Hz, 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 (100 MHz, CD ₃ OD) δ 175.00, 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.

¹ H NMR (400MHz, CD ₃ OD) δ 7.75 (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. ^13C NMR(101MHz, _CD3OD )δ174.63,142.50,136.26,133.82,132.76,131.86,131.16,130.98,128.65,64.21,39.78,37.11,33.34,26.2ppm EI-TOF)calcd for C ₁₇ H ₁₉ ³⁵ ClN ₂ S[M ⁺ ]m/z 318.0957,found318.0956.calcd for C ₁₇ H ₁₉ ³⁷ ClN ₂ S[M ⁺ ]m/z 320.0928,found 320.0930.

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.87 (d, J=1.3 Hz, 1H), 7.32 (t, J=8.1 Hz, 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, 6.2 Hz, 2H) ppm. ¹³ C NMR (101 MHz, 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,found380.0359.calcd for C ₁₇ H ₁₈ ⁸¹ BrFN ₂ S[M ⁺ ]m/z 382.0338,found 382.0338.

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.75 (s, 1H), 7.40 (d, J=8.1 Hz, 2H), 7.18 (d, J=7.9 Hz, 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.

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 forC ₁₉ H ₂₄ N ₂ S[M ⁺ ]m /z 312.1660,found 312.1663.

¹ H NMR (400MHz, CDCl ₃ ) δ 7.72 (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 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.

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.83 (s, 1H), 7.59 (d, J=8.4 Hz, 2H), 7.53 (d, J=8.4 Hz, 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, 5.8 Hz, 2H) ppm. ¹³ C NMR (101 MHz, 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 forC ₁₈ H ₁₉ N ₃ S[M ⁺ ]m/z 309.1 found 309.1299.

¹ H NMR (400MHz, CDCl ₃ ) δ 7.77(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, 6.3 Hz, 2H) ppm. ¹³ C NMR (101 MHz, CDCl ₃ ) δ 175.82, 148.72, 137.83, 136.52, 130.43, 127.87, 121.45, 120.38 (q, J=257.6 Hz) .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.

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.71 (s, 1H), 7.26-7.22 (m, 2H), 7.18 (t, J=7.4 Hz, 1H), 7.04 (d, J=7.1 Hz, 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 (101 MHz, CDCl ₃ ) δ 171.73, 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 forC ₁₈ H ₂₂ N ₂ S[M ⁺ ]m/z 298.1504,found 298.1503.

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.72 (s, 1H), 7.21 (t, J=7.9 Hz, 1H), 7.03 (d, J=7.5 Hz, 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 (101 MHz, CDCl ₃ ) δ 172.29, 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.

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, 5.8 Hz, 2H) ppm. ¹³ C NMR (101 MHz, CDCl ₃ ) δ 176.11, 138.80, 135.55, 135.43, 134.44, 127.77, 124.83, 61.27, 39.72, 37.51, 33.91, 26.03 ppm. HRMS ( EI-TOF)calcd for C ₁₇ H ₁₈ ³⁵ Cl ₂ N ₂ S[M ⁺ ]m/z 352.0568,found352.0567.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.

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, 5.9 Hz, 2H) ppm. ¹³ C NMR (101 MHz, CDCl ₃ ) δ 172.46, 161.96 (d, J=246.7 Hz), 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.

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.73 (s, 1H), 7.42 (t, J=1.6 Hz, 1H), 7.31 (dt, J=7.3, 1.6 Hz, 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 ₂ S[ ₁₇ H ₁₉ ³⁵ M ⁺ ]m/z 318.0957,found318.0961.calcd for C ₁₇ H ₁₉ ³⁷ ClN ₂ S[M ⁺ ]m/z 320.0928,found 320.0932.

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.78 (s, 1H), 7.66 (s, 1H), 7.61 (d, J=7.6 Hz, 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 ) δ 172.37, 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.

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.69 (s, 1H), 7.59 (dd, J=8.0, 1.1 Hz, 1H), 7.36 (dd, J=7.7, 1.7 Hz, 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 ¹³ C NMR (101MHz, CDCl ₃ ) δ 173.06, 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 ^HRMS BrN ₂ S[M ⁺ ]m/z 362.0452,found362.0453.calcd for C ₁₇ H ₁₉ ⁸¹ BrN ₂ S[M ⁺ ]m/z 364.0432,found 364.0432.

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.92 (s, 1H), 7.48 (d, J=7.4 Hz, 1H), 7.21 (t, J=7.6 Hz, 1H), 6.91 (t, J=8.9 Hz) ,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 forC ₁₈ H ₂₂ N ₂ OS[M ⁺ ]m/z 314.1453,found 314.1452.

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, 6.0 Hz, 2H) ppm. ¹³ C NMR (101 MHz, CDCl ₃ ) δ 173.50, 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.

¹ H NMR (400 MHz, CDCl ₃ ) δ 8.54 (d, J=2.2 Hz, 1H), 7.84 (s, 1H), 7.77 (dd, J=8.3, 2.5 Hz, 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,found319.0912.calcd for C ₁₆ H ₁₈ ³⁷ ClN ₃ S[M ⁺ ]m/z 321.0880,found 321.0881.

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.77 (s, 1H), 7.38 (s, 1H), 7.34 (d, J=8.3 Hz, 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 )δ170.76,138.55,137.62,136.87,134.42,129.64,129.59,129.12,125.26,63.02,34.52,32.38,20.02ppm .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 .

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.70 (s, 1H), 7.33-7.26 (m, 2H), 7.00 (t, J=8.9 Hz, 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 (101 MHz, CDCl ₃ ) δ 174.9, 161.1 (d, J=246.8 Hz), 137.3, 137.1 (d, J=0.9 Hz), 129.7 (d, J=5.3 Hz), 127.5 (d, J=5.3 Hz) ＝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,found316.1408.

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.77 (s, 1H), 7.50 (d, J=8.3 Hz, 1H), 7.36 (d, J=1.9 Hz, 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, 6.3 Hz, 2H) ppm. ¹³ C NMR (101 MHz, CDCl ₃ ) δ 175.20, 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/z378.0588,found 378.0590.

¹ H NMR (400MHz, CDCl ₃ ) δ 7.72(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 for C HRMS (EI- _TOFcalc ) ₂₄ N ₂ S[M ⁺ ]m/z 312.1660,found312.1661.

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, ^13C 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, 22.90 ppm. HRMS (EI-TOFcalc for _ppm.HRMS ) H ₂₆ N ₂ S[M ⁺ ]m/z 326.1817, found326.1819.

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.75 (s, 1H), 7.45 (d, J=8.4 Hz, 2H), 7.39 (d, J=8.4 Hz, 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 ) δ 174.8, 151.2, 138.1, 137.0, 128.8, 126.4, 125.9, 61.1, 39.9, 37.9, 34.6, 34.0, 31.2, 26.2 ppm.HRMS(EI-TOF)calcd for C ₂₁ H ₂₈ N ₂ S[M ⁺ ]m/z 340.1973, found 340.1974.

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.79 (s, 1H), 7.70 (dt, J=8.9, 1.8 Hz, 2H), 7.25 (dt, J=8.7, 2.1 Hz, 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 (101 MHz, CDCl ₃ ) δ 175.5, 138.1, 137.8, 137.1, 131.2, 128.2, 93.3, 61.1, 39.8, 37.7, 34.0, 26.1 ppm. HRMS (EI-TOF) calcd for C ₁₇ H ₁₉ IN ₂ S [M ⁺ ]m/z 410.0314, found 410.0316.

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.74 (s, 1H), 7.56 (d, J=1.6 Hz, 1H), 7.46 (d, J=8.6 Hz, 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, 3.0 Hz, 2H), 1.73 (dd, J=14.4, 6.1 Hz, 2H) ppm. ¹³ C NMR (101 MHz, CDCl ₃ ) δ 177.0, 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,found446.0276.calcd for C ₁₈ H ₁₈ ⁸¹ BrF ₃ N ₂ OS[M ⁺ ]m/z 448.0255,found 448.0254.

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.79 (s, 1H), 7.78 (s, 1H), 7.46 (dd, J=8.5, 2.0 Hz, 1H), 7.31 (d, J=8.4 Hz, 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 (101 MHz, CDCl ₃ ) δ 176.5, 145.9 (q, J=1.5 Hz), 138.6, 135.1, 132.0, 131.7, 126.7, 122.6, 120.4 (q, J=259.6 Hz), 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.

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, 6.2 Hz, 2H) ppm. ¹³ C NMR (101 MHz, CDCl ₃ ) δ 175.3, 138.9, 137.4, 137.1, 130.0, 126.1, 61.0, 39.9, 37.9, 34.0, 26.2, 23.8 ppm. 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.

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.80 (s, 1H), 7.50 (d, J=8.6 Hz, 1H), 7.37 (d, J=1.7 Hz, 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.

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.84 (s, 1H), 7.62-7.57 (m, 6H), 7.45 (t, J=7.6 Hz, 2H), 7.36 (t, J=7.3 Hz, 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, 3.1 Hz, 2H), 1.73 (dd, J=14.3, 6.3 Hz, 2H) ppm. ¹³ C NMR (101 MHz, CDCl ₃ ) δ 175.30, 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.

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.87 (s, 1H), 7.73 (s, 1H), 7.62 (d, J=7.4 Hz, 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, 2.8 Hz, 2H), 1.74 (dd, J=14.4, 6.2 Hz, 3H) ppm. ¹³ C NMR (101 MHz, CDCl ₃ ) δ 175.35, 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)calc SM ₂₄ N ₂₃ H for C ₂₃ H ⁺ ]m/z 360.1660,found360.1662.

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 forC 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/z396.1241,found 396.1249.

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 ) δ 174.95, 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 ppm. for C ₂₃ H ₂₄ N ₂ OS[M ⁺ ]m/z376.1609, found 376.1612.

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.86 (d, J=3.7 Hz, 1H), 7.62 (d, J=5.0 Hz, 1H), 7.18 (t, J=4.4 Hz, 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 )δ173.51,171.07,153.35,131.77,131.65,128.43,125.92,79.40,53.46,52.72,35.08,34.60,28.52,27.6.29,2 ppm.HRMS(EI-TOF)calcd for C ₁₈ H ₂₃ N ₃ O ₃ S[M ⁺ ]m/z361.1460,found 361.1462.

¹ H NMR (400MHz, CDCl ₃ ) δ 8.17-8.14(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, found439.1723.

¹ H NMR (400 MHz, CDCl ₃ ) δ 8.18 (d, J=8.0 Hz, 2H), 7.74 (d, J=8.1 Hz, 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) _{calcdfor C21H24F3N3O3 [ M} ⁺ ] _m /z 423.1770,found 423.1767.

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 (101 MHz, 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/z275.1092,found 275.1093 .

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.93 (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– _HRMS ^_ TOF)calcd for C ₁₇ H ₂₁ N ₃ O[M ⁺ ]m/z 283.1685,found283.1683.

¹ H NMR (400 MHz, CDCl ₃ ) δ 8.17 (d, J=8.8 Hz, 2H), 7.36 (d, J=8.2 Hz, 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.

¹ H NMR (400 MHz, CDCl ₃ ) δ 8.21 (d, J=8.3 Hz, 2H), 7.75 (d, J=8.4 Hz, 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 (101 MHz, CDCl ₃ ) δ 174.24, 173.95, 134.00 (q, J=32.9 Hz), 128.37, 127.47, 126.02 (q, J=3.7 Hz), 123.45 (q, J=272.7 Hz) ),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.

¹ H NMR (400 MHz, CDCl ₃ ) δ 8.01 (d, J=8.5 Hz, 2H), 7.46 (d, J=8.5 Hz, 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.

¹ H NMR (400 MHz, CDCl ₃ ) δ 8.09 (dt, J=9.5, 2.7 Hz, 2H), 7.42 (d, J=7.1 Hz, 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, 6.4 Hz, 2H) ppm. ¹³ C NMR (101 MHz, CDCl ₃ ) δ 169.87, 163.55, 151.38, 139.49, 128.83, 128.57, 128.53, 128.36, 128.26, 126.93, 122.33(121.25, 121.20 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.

¹ H NMR (400 MHz, CDCl ₃ ) δ 8.20 (d, J=8.1 Hz, 2H), 7.87 (dd, J=6.4, 2.7 Hz, 2H), 7.74 (d, J=8.3 Hz, 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 ) δ 167.16, 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.

¹ H NMR (400 MHz, CDCl ₃ ) δ 8.07 (d, J=8.8 Hz, 2H), 7.34 (d, J=8.3 Hz, 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.

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.85 (s, 1H), 7.81 (d, J=7.6 Hz, 1H), 7.37 (t, J=7.6 Hz, 1H), 7.32 (d, J=7.7 Hz ,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, 6.2 Hz, 2H) ppm. ¹³ C NMR (101 MHz, CDCl ₃ ) δ 169.05, 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.

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.90 (d, J=8.9 Hz, 2H), 6.94 (d, J=8.9 Hz, 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, 6.1 Hz, 2H) ppm. ¹³ C NMR (101 MHz, 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.

¹ H NMR (400 MHz, CDCl ₃ ) δ 8.01 (d, J=6.6 Hz, 2H), 7.49 (d, J=6.4 Hz, 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. 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.

¹ H NMR (400 MHz, CDCl ₃ ) δ 8.15 (d, J=8.2 Hz, 2H), 7.76 (d, J=8.3 Hz, 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, 2.8 Hz, 2H), 1.73 (dd, J=14.6, 6.3 Hz, 2H) ppm. ¹³ C NMR (101 MHz, 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,found337.1403.

¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.22 (d, J=8.1 Hz, 2H), 7.99 (d, J=8.1 Hz, 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 (101 MHz, DMSO-d ₆ ) δ 168.13, 162.98, 131.47 (q, J=32.4 Hz), 127.31, 127.10, 126.41 (q, J=3.6 Hz), 123.67 (q, J=272.4 Hz) ,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.

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.97 (d, J=8.7 Hz, 2H), 7.31 (d, J=8.6 Hz, 2H), 3.58 (tt, J=11.8, 5.6 Hz, 1 H), 3.36 ^13C 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,found369.1122.

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.75 (s, 1H), 7.69 (d, J=7.6 Hz, 1H), 7.34 (t, J=7.6 Hz, 1H), 7.27 (d, J=8.2 Hz ,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, 6.3 Hz, 2H) ppm. ¹³ CNMR (101 MHz, CDCl ₃ ) δ 174.80, 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 C17H21N3S _[ M ⁺ ]m/ _z299.1456 ,found 299.1457.

¹ H NMR (400 MHz, CDCl ₃ ) δ 8.16 (d, J=8.2 Hz, 2H), 7.76 (d, J=8.3 Hz, 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.

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.83 (dt, J=9.6, 2.8 Hz, 2H), 7.54 (d, J=2.4 Hz, 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 (101 MHz, CDCl ₃ ) δ 153.60, 149.06, 148.57 (q, J=1.7 Hz), 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,found471.1772.

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.92 (d, J=8.1 Hz, 2H), 7.63 (d, J=8.2 Hz, 2H), 7.56 (d, J=2.4 Hz, 1 H), 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 (101 MHz, CDCl ₃ ) δ 153.60, 148.89, 137.12 (q, J=2.7 Hz), 136.87, 129.58, 129.27 (q, J=32.4 Hz), 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/z455.1821,found 455.1823.

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.84 (d, J=8.7 Hz, 2H), 7.56 (d, J=2.2 Hz, 1H), 7.23 (d, J=8.2 Hz, 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, 6.3 Hz, 2H) ppm. ¹³ C NMR (101 MHz, CDCl ₃ ) δ 148.87, 148.44 (q, J=1.5 Hz), 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.

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.65 (s, 1H), 7.61 (d, J=7.7 Hz, 1H), 7.54 (d, J=2.3 Hz, 1H), 7.27 (t, J=7.6 Hz) ,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 C ₁₈ H ₂₃ N ₃ [M ⁺ ]m/z 281.1892, found 281.1894.

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.75 (d, J=8.7 Hz, 2H), 7.53 (d, J=1.9 Hz, 1H), 6.92 (d, J=8.6 Hz, 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) _a ^_ 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.

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.83 (d, J=7.7 Hz, 2H), 7.55 (d, J=1.7 Hz, 1H), 7.38 (t, J=7.6 Hz, 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, 6.3 Hz, 2H) ppm. ¹³ C NMR (101 MHz, CDCl ₃ ) δ 150.13, 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/z301.1346,found 301.1343.calcd for C ₁₇ H ₂₀ ³⁷ ClN ₃ [M ⁺ ]m/z 303.1316, found 303.1317.

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.93 (d, J=8.2 Hz, 2H), 7.63 (d, J=8.2 Hz, 2H), 7.59 (d, J=2.1 Hz, 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, 6.4 Hz, 2H) ppm. ¹³ C NMR (101 MHz, CDCl ₃ ) δ 148.71, 137.37, 129.42, 129.08 (q, J=32.3 Hz), 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.

¹ H NMR (400MHz, CDCl ₃ ) δ 7.81-7.79 (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,found393.1610.calcd for C ₂₃ H ₂₄ ³⁷ ClN ₃ O[M ⁺ ]m/z 395.1578,found 395.1581.

¹ H NMR (400MHz, CDCl ₃ ) δ 7.52 (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 for EI-TOF)calcd C ₁₈ H ₂₁ N ₃ O ₂ [M ⁺ ]m/z 311.1634, found311.1632.

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, 6.3 Hz, 2H) ppm. ¹³ C NMR (101 MHz, 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 3} O[M ⁺ ]m/z 359.1998, found359.1999.

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.87 (d, J=8.7 Hz, 2H), 7.56 (d, J=2.2 Hz, 1H), 7.30 (d, J=8.7 Hz, 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 )calcd for C ₂₀ H ₂₂ N ₄ OS[M ⁺ ]m/z 366.1514,found366.1510.

¹ H NMR (400 MHz, CDCl ₃ ) δ 8.03 (d, J=4.8 Hz, 1H), 7.87 (d, J=8.6 Hz, 2H), 7.76 (d, J=7.7 Hz, 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, 6.3 Hz, 2H) ppm. ¹³ C NMR (101 MHz, CDCl ₃ ) δ 159.16, 152.84, 149.53, 145.19, 139.24, 131.13, 129.06, 126.67, 121.57, 119.18, 119.06, 519.45, 59. ,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 /z396.1531,found 396.1530.

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 (101 MHz, CDCl ₃ ) δ 153.53, 136.23 (q, J=1.3 Hz), 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.

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.79 (s, 1H), 7.76 (s, 1H), 7.49 (d, J=8.8 Hz, 2H), 7.21 (d, J=8.0 Hz, 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)79.56,53.10,51.97,51.11,34.52,2.5.07,2 ,28.15ppm.HRMS(EI-TOF)calcd for C ₂₂ H ₂₆ F ₃ N ₃ O ₃ [M ⁺ ]m/z437.1926,found 437.1928.

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.72 (s, 2H), 7.41 (d, J=8.8 Hz, 2H), 6.91 (d, J=8.7 Hz, 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, 6.3 Hz, 2H) ppm. ¹³ C NMR (101 MHz, CDCl ₃ ) δ 158.25, 135.49, 126.63, 125.51, 124.31, 122.45, 114.27, 59.44, 55.33, 52.17, 40.31, 35.36, 25.92 ppm. HRMS ( EI-TOF)calcd for C ₁₈ H ₂₃ N ₃ O[M ⁺ ]m/z 297.1841, found 297.1845.

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.78 (s, 1H), 7.77 (s, 1H), 7.29 (d, J=9.8 Hz, 2H), 7.24 (t, J=7.5 Hz, 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 (101 MHz, CDCl ₃ ) δ 138.38, 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 forC ₁₈ H ₂₃ N ₃ [M ⁺ ]m/z 281.1892,found 281.1895.

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.77 (s, 1H), 7.75 (s, 1H), 7.40 (d, J=8.4 Hz, 2H), 7.31 (d, J=8.3 Hz, 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, 6.0 Hz, 2H) ppm. ¹³ C NMR (101 MHz, CDCl ₃ ) δ 135.71, 131.80, 131.35, 128.92, 126.63, 124.90, 121.59, 59.36, 52.42, 40.35, 35.50, 26.03 ppm. 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.

¹ H NMR (400MHz, CDCl ₃ ) δ 7.85 (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, 6.0 Hz, 2H) ppm. ¹³ C NMR (101 MHz) , 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, found335.1612.

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.78 (s, 1H), 7.75 (s, 1H), 7.48 (d, J=8.5 Hz, 2H), 7.20 (d, J=8.1 Hz, 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, 6.2 Hz, 2H) ppm. ¹³ C NMR (101 MHz, CDCl ₃ ) δ 147.55 (q, J=1.7 Hz), 135.76, 131.73, 126.61, 124.99, 121.46, 120.50 (d, J=256.9 Hz) ,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,found351.1561.

¹ H NMR (400 MHz, CDCl ₃ ) δ 8.66 (d, J=8.4 Hz, 1H), 8.05 (s, 1H), 7.99 (s, 1H), 7.74 (d, J=8.4 Hz, 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 (101 MHz, CDCl ₃ ) δ 153.52, 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 _{C24H26F3N3O2 [ M} ⁺ ] _m /z 445.1977,found 445.1973.

¹ H NMR (400MHz, CDCl ₃ ) δ 8.43(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 (101 MHz, CDCl ₃ ) δ 153.99, 137.77, 131.55, 129.36, 128.34, 127.75, 126.40 (q, J=32.4 Hz), 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)calcdfor C ₂₄ H ₂₆ F ₃ N ₃ O ₂ [M ⁺ ]m/z 445.1977,found 445.1976.

¹ H NMR (400MHz, CDCl ₃ ) δ 8.48(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 (101 MHz, CDCl ₃ ) δ 153.59, 147.12, 129.81, 129.58, 127.56, 126.84 (q, J=32.2 Hz), 126.07 (q, J=4.1 Hz),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.

¹ H NMR (400 MHz, CDCl ₃ ) δ 8.69 (d, J=8.4 Hz, 1H), 8.07 (s, 1H), 8.06 (s, 1H), 7.75 (dd, J=8.3, 1.2 Hz, 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 (101 MHz, CDCl ₃ ) δ 144.46, 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.

¹ H NMR (400 MHz, CDCl ₃ ) δ 8.38 (s, 1H), 8.22 (d, J=8.1 Hz, 1H), 7.89 (d, J=8.0 Hz, 1H), 7.68 (d, J=9.1 Hz ,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 36.96,27.07ppm.HRMS(EI-TOF)calcd forC ₁₉ H ₂₁ N ₃ [M ⁺ ]m/z 291.1735, found 291.1738.

¹ H NMR (400 MHz, CDCl ₃ ) δ 8.34 (s, 1H), 8.14 (d, J=8.6 Hz, 1H), 7.86 (d, J=2.1 Hz, 1H), 7.59 (d, J=9.1 Hz ,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＝14.6,7.6 Hz, 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 ppm. CDCl ₃ )showed a crosspeak from δ2.22,2.65,4.96 to δ7.56.HRMS(EI-TOF)calcd for C ₁₉ H ₂₀ ³⁵ ClN ₃ [M ⁺ ]m/z325.1346,found 325.1345.calcd for C ₁₉ H ₂₀ ³⁷ ClN ₃ [M ⁺ ]m/z 327.1316, found 327.1322.

¹ H NMR (400MHz, CDCl ₃ ) δ 8.42(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.

¹ H NMR (400 MHz, CDCl ₃ ) δ 8.40 (s, 1H), 8.05 (d, J=7.9 Hz, 1H), 7.80 (d, J=7.9 Hz, 1H), 7.66 (d, J=9.2 Hz) ,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 )δ146.75,130.20,128.83,127.69,127.59,126.55,124.85,123.16,121.27,118.17,117.88,59.46,53.51,40.32,35.9ppm. )calcd for C ₁₉ H ₂₁ N ₃ [M ⁺ ]m/z 291.1735, found291.1737.

¹ H NMR (400 MHz, CDCl ₃ ) δ 8.37 (s, 1H), 7.97 (d, J=8.5 Hz, 1H), 7.77 (d, J=2.1 Hz, 1H), 7.68 (d, J=9.2 Hz ,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, 6.3 Hz, 2H) ppm. ¹³ CNMR (101 MHz, CDCl ₃ ) δ 146.59, 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 _forC19H20 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.

¹ H NMR (400 MHz, CDCl ₃ ) δ 8.48 (s, 1H), 8.15 (d, J=8.4 Hz, 1H), 8.09 (s, 1H), 7.75 (d, J=9.2 Hz, 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, 4.0 Hz, 4H), 2.31 (s, 3H), 1.99–1.96 (m, 2H), 1.62–1.56 (m, 2H) ppm. ¹³ C NMR (101 MHz, CDCl ₃ ) δ 147. 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 compounds of the invention.

The selected pine wood nematode (Bursaphelenchus xylophilus) and southern root knot nematode (Meloidogyne incongnita) were purchased from Huzhou Modern Agriculture Center, Chinese Academy of Sciences, and were used to test and determine the nematicidal activity of the compounds of the present invention.

Specific test operation process:

An electronic analytical balance accurately weighs the positive control drug and the target compound, dissolves them in dimethyl sulfoxide, and then dilutes them with an aqueous solution containing 0.2% triton to form a mother liquor of a certain concentration, in which the content of organic solvent in water is less than 1%. , the concentration of the mother liquor is 2 times of the highest concentration required for the test. In the actual test, an appropriate amount of mother liquor and an aqueous solution containing 0.2% triton were respectively diluted to the required concentration for use. The prepared drug solution was added to a 96-well plate, 50 μL per well, and each drug was repeated twice. Add 50 μL of nematode suspension (about 50 nematodes) to the drug with a continuous sampler, and place the lid in an observation room at 22±1°C. The aqueous solution of 0.2% triton per milliliter contained 4uL dimethyl sulfoxide as the CK control group, and abamectin (5ppm) and fluthiandin (5ppm) were the positive control groups. , Check the number of nematode deaths in 72 hours, and calculate the average mortality of nematodes in two repeated experiments.

Adjusted death rate = (death rate of treatment group - death rate of control group) / (1 - death rate of control group) × 100%

Table 1 Lethality (%) of the compounds of the present invention to two nematodes at a concentration of 40 ppm

It can be seen from Table 1 that some compounds have excellent nematicidal activity at a concentration of 40 ppm.

All documents mentioned herein are incorporated by reference in this application as if each document were individually incorporated by reference. In addition, it should be understood that after reading the above teaching content of the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by the appended claims of the present application.

Claims (10)

1. A compound shown in a general formula I, or an optical isomer, a cis-trans isomer and an agriculturally and pharmaceutically acceptable salt thereof,

in the formula,

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 aryl-C1-C15 alkoxycarbonyl; said 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;

X₁is CH ═ CH or is absent, X₂Is CH ═ CH or is absent, and when X is present₁When CH is CH, X is absent₂(ii) a When X is present₂Is CH ═ CH, in the absence of X₁；

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; r¹Is a substituent on Ar, in a number of 0, 1,2, 3 or 4, each R¹Each 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-OAr¹(ii) a Wherein Ar is¹Is a C6-C10 aryl, 5-or 6-membered heteroaryl, or 8-12 membered heteroaryl 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.

2. The compound of claim 1, wherein when D is S or O, B is C, A is N, E is N or C (H), X is₁And X₂Is absent.

3. The compound of claim 1, wherein X is X when D is N, B is C, A is S or N, E is CH or O₁And X₂Is absent.

4. The compound of claim 1, wherein X is when D is CH or N, B is N, A is CH or N, E is C₂Is CH ═ CH;

when D is C, B is N, A is N, E is CH, X₁Is CH ═ CH; or

When D is CH or N, B is N, A is CH or N, E is CH, X₁And X₂Is absent.

5. The compound of claim 1, wherein the compound has a structure selected from the group consisting of:

wherein Ar is as defined in claim 1, optionally having 1,2 or 3 substituents R¹；

R、R¹Is as defined in claim 1.

6. A compound according to claim 1 or 5 wherein Ar is a phenyl ring, a naphthyl ring, a 5-6 membered heteroaromatic ring or an 8-10 membered heteroaromatic bicyclic ring system, optionally having 1,2 or 3 substituents R¹；

In the formulae, each R¹Each independently selected from: C1-C6 alkyl, C1-C4 alkoxy, fluorine, chlorine, bromine, halogenated C1-C4 alkyl, halogenated C1-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.

7. The compound of claim 1, wherein the compound is selected from the group consisting of:

8. a pesticidal composition comprising a compound according to any one of claims 1 to 7 or an agriculturally pharmaceutically acceptable salt thereof; and an agriculturally acceptable carrier.

9. Use of a compound according to any one of claims 1 to 7 or an agriculturally pharmaceutically acceptable salt thereof or a pesticidal composition according to claim 8 for nematicidal or nematicidal purposes; or for the preparation of a medicament for killing or preventing nematodes.

10. A method of killing or preventing nematodes including applying a compound according to any one of claims 1 to 7 or an agriculturally acceptable salt thereof or a pesticidal composition according to claim 8 to a plant suffering from or susceptible to a pest, or to the soil or environment surrounding the plant.