Fluorinated sulfur-containing nitrogen-containing heterocyclic compound as well as synthesis method and application thereof

Abstract

The invention discloses a fluorinated sulfur-containing and nitrogen-containing heterocyclic compound as well as a synthesis method and application thereof. According to the method, raw materials which are easy to prepare and an iodine (III) oxidant and a fluorine source which are easy to obtain are subjected to a sulfur-fluorine olefin dual-functionalization reaction or a sulfur-fluorine olefin dual-functionalization reaction after hydrolysis in an organic solvent at room temperature to obtain the target compound. The synthesis method of the target compound has the advantages of simplicity in operation, mild conditions and wide substrate application range.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of synthetic medicine, pharmaceutical intermediates, and chemical industry, and mainly relates to a class of fluorinated sulfur-containing and nitrogen-containing heterocyclic compounds and a synthesis method and application thereof. BACKGROUND

[0002] Thiazolidine and thiazinane are a class of very important sulfur-containing and nitrogen-containing five-membered / six-membered heterocyclic compounds, and are basic unit structures in numerous drug molecules. In recent years, the biological activity of the derivative structures of thiazolidine and thiazinane has been widely studied. The compounds have a wide application in drugs, including anti-depression, anti-hypertension, anti-inflammatory, anti-Alzheimer's disease, insecticidal activity, use as a progesterone receptor binding agent, antibacterial, anti-tumor, antioxidant, antipyretic activity, use as a calcium channel modulator and cannabinoid receptor ligand, anti-HIV, anti-convulsant, bactericidal, insecticidal, use as an agonist of EP4, and use as a prostaglandin E2 receptor subtype for treating glaucoma. The introduction of fluorine into a molecule often improves metabolic stability, improves the lipophilicity of the molecule, and thus is conducive to improving the bioavailability. Therefore, it is of great research value to synthesize diverse and multifunctional thiazolidine and thiazinane compounds, and to develop a simple and efficient method for synthesizing fluorinated thiazolidine and thiazinane compounds. SUMMARY

[0003] The present application aims at providing a kind of fluorinated sulfur-containing nitrogen-containing heterocyclic compounds (including (Z)-N-(5-(fluoromethyl / 1-fluoroalkyl / fluoro (aryl) methyl)-3-alkyl / substituted alkyl / aryl thiazolidine-2-ylidene)-alkyl / aryl carboxamide compounds, (Z)-N-(6-(fluoromethyl / 1-fluoroalkyl-3-alkyl / substituted alkyl / aryl (fluoroethyl)-1,3-thiazolidine-2-ylidene) alkyl / aryl carboxamide compounds, N-((2Z,5E)-5-(1-fluoroethylene / 1-fluoroalkylene / 1-fluoro-substituted alkyl)-3-alkyl / substituted alkyl / aryl thiazolidine-2-ylidene) alkyl / aryl amide compounds, 5-(2-fluoroprop-2-yl / 2-fluoro-substituted alkyl / fluoromethyl / fluoro (aryl) methyl)) thiazolidine-2-ketone compounds and 6-(2-fluoroprop-2-yl / 2-fluoro-substituted alkyl / fluoromethyl / fluoro (aryl) methyl))-1,3-thiazolidine-2-ketone compounds) and a synthesis method thereof, which uses easily prepared raw materials and easily obtained high-valence iodine (III) oxidants and fluorine sources to occur sulfur fluorine olefin / alkyne bifunctionalization reaction or hydrolysis after sulfur fluorine olefin bifunctionalization reaction, to synthesize (Z)-N-(5-(fluoromethyl / 1-fluoroalkyl / fluoro (aryl) methyl)-3-alkyl / substituted alkyl / aryl thiazolidine-2-ylidene)-alkyl / aryl carboxamide compounds, (Z)-N-(6-(fluoromethyl / 1-fluoroalkyl-3-alkyl / substituted alkyl / aryl (fluoroethyl)-1,3-thiazolidine-2-ylidene) alkyl / aryl carboxamide compounds, N-((2Z,5E)-5-(1-fluoroethylene / 1-fluoroalkylene / 1-fluoro-substituted alkyl)-3-alkyl / substituted alkyl / aryl thiazolidine-2-ylidene) alkyl / aryl amide compounds, 5-(2-fluoroprop-2-yl / 2-fluoro-substituted alkyl / fluoromethyl / fluoro (aryl) methyl)) thiazolidine-2-ketone compounds and 6-(2-fluoroprop-2-yl / 2-fluoro-substituted alkyl / fluoromethyl / fluoro (aryl) methyl))-1,3-thiazolidine-2-ketone compounds with medium to good yield. The method has the advantages of simple operation, mild conditions and wide substrate applicability.

[0004] The present application proposes a kind of (Z)-N-(5-(fluoromethyl / 1-fluoroalkyl / fluoro (aryl) methyl)-3-alkyl / substituted alkyl / aryl thiazolidine-2-ylidene)-alkyl / aryl carboxamide compounds and (Z)-N-(6-(fluoromethyl / 1-fluoroalkyl-3-alkyl / substituted alkyl / aryl (fluoroethyl)-1,3-thiazolidine-2-ylidene) alkyl / aryl carboxamide compounds, which have the following formula (2) structure:

[0005]

[0006] Wherein,

[0007] R1 is alkyl, substituted alkyl or aryl;

[0008] R 2 is alkyl, substituted alkyl, aryl or heteroaryl;

[0009] R 3 is hydrogen or alkyl;

[0010] R 4 , R 5 are each independently hydrogen, alkyl, substituted alkyl or aryl;

[0011] R 6 is hydrogen, alkyl, substituted alkyl or aryl;

[0012] wherein the aryl includes p-fluorophenyl, p-chlorophenyl, p-bromophenyl, p-iodophenyl, p-trifluoromethylphenyl, p-methoxyphenyl, p-esterphenyl, o-fluorophenyl, m-fluorophenyl, m-methoxyphenyl; the heteroaryl includes 3-furyl, 2-thienyl; the alkyl and substituted alkyl include benzyl, diphenylmethyl, 2-(2-thienyl)ethyl, 2-(phenyl)ethyl, 2-(phenoxy)ethyl, 4-N-Boc-piperidyl, t-butyl, cyclohexyl, methyl, n-butyl, n-propyl.

[0013] The present application also provides a synthesis method of (Z)-N-(5-(fluoromethyl / 1-fluoroalkyl / fluoro(aryl)methyl)-3-alkyl / substituted alkyl / arylthiazolidine-2-ylidene)-alkyl / arylcarboxamide and (Z)-N-(6-(fluoromethyl / 1-fluoroalkyl-3-alkyl / substituted alkyl / aryl(fluoroethyl)-1,3-thiazolidine-2-ylidene)alkyl / arylcarboxamide, comprising: subjecting N-(high)allyl-N-(alkyl / substituted alkyl / aryl)thiocarbamoyl)alkyl / aryl amide, iodine (III) oxidant and fluorine source to a sulfur-fluoro olefin bifunctionalization reaction in an organic solvent at room temperature to obtain the (Z)-N-(5-(fluoromethyl / 1-fluoroalkyl / fluoro(aryl)methyl)-3-alkyl / substituted alkyl / arylthiazolidine-2-ylidene)-alkyl / arylcarboxamide and (Z)-N-(6-(fluoromethyl / 1-fluoroalkyl-3-alkyl / substituted alkyl / aryl(fluoroethyl)-1,3-thiazolidine-2-ylidene)alkyl / arylcarboxamide; the process is shown in the following reaction formula (I):

[0014]

[0015] wherein,

[0016] R 1 , R 2 , R 3 , R4 R 5 R 6 The definition is the same as shown in equation (2).

[0017] Wherein, the molar ratio of N-((high)allylthiocarbonyl)alkyl / aryl formamide to iodine(III) oxidant shown in formula (1) is 1:(1-3); preferably, it is 1:1.15;

[0018] Wherein, the molar ratio of N-((high)allylthiocarbonyl)alkyl / aryl formamide shown in formula (1) to the fluorine source is 1:(1-20); preferably, it is 1:9.

[0019] The iodine (III) oxidant is PhI(OPiv)2, PhI(OAc)2, or PhI(OAd)2; preferably, it is PhI(OPiv)2.

[0020] The fluorine source is Et3N·3HF or py·8HF; preferably, it is Et3N·3HF.

[0021] The organic solvent is acetonitrile, dichloromethane, toluene, 1,4-dioxane, diethyl ether, xylene, chlorobenzene, and trifluorotoluene; preferably, it is toluene.

[0022] The reaction time is 1-8 hours; preferably, it is 2 hours.

[0023] The method of the present invention further includes post-processing and column chromatography separation and purification steps; wherein the separation and purification is performed by column chromatography using a mixed solvent of petroleum ether and ethyl acetate or other mixed solvents as eluents.

[0024] In one specific embodiment, the method of the present invention includes: placing N-(high)allyl-N-(alkyl / substituted alkyl / aryl)aminethiocarbamoyl)alkyl / aryl amide, iodine (III) oxidant and fluorine source in an organic solvent at room temperature, and monitoring by TLC until the reactant (1) is completely reacted; quenching the reaction system with saturated sodium bicarbonate solution, extracting three times with dichloromethane, washing the combined organic layers with saturated brine, then concentrating the organic phase under reduced pressure, and separating the residue by column chromatography using a certain proportion of eluent to obtain (Z)-N-(5-(fluoromethyl / 1-fluoroalkyl / fluoro(aryl)methyl)-3-alkyl / substituted alkyl / arylthiazolyl-2-methylene)-alkyl / aryl carboxamide compounds and (Z)-N-(6-(fluoromethyl / 1-fluoroalkyl-3-alkyl / substituted alkyl / aryl(fluoroethyl)-1,3-thiazinane-2-methylene)alkyl / aryl carboxamide compounds as shown in formula (2).

[0025] The application provides a method for synthesizing (Z)-N-(5-(fluoromethyl / 1-fluoroalkyl / fluoro(aryl)methyl)-3-alkyl / substituted alkyl / aryl thiazolidine-2-ylidene)-alkyl / aryl formamides and (Z)-N-(6-(fluoromethyl / 1-fluoroalkyl-3-alkyl / substituted alkyl / aryl(fluoroethyl)-1,3-thiazolidine-2-ylidene)alkyl / aryl formamides, which comprises the following steps: in an organic solvent, at room temperature, N-(high) allyl-N-(alkyl / substituted alkyl / aryl) amine thioformyl) alkyl / aryl amide, iodine (III) oxidant and fluorine source are subjected to sulfur-fluoro olefin bifunctionalization reaction to obtain the (Z)-N-(5-(fluoromethyl / 1-fluoroalkyl / fluoro(aryl)methyl)-3-alkyl / substituted alkyl / aryl thiazolidine-2-ylidene)-alkyl / aryl formamides and (Z)-N-(6-(fluoromethyl / 1-fluoroalkyl-3-alkyl / substituted alkyl / aryl(fluoroethyl)-1,3-thiazolidine-2-ylidene)alkyl / aryl formamides; after post-treatment and column chromatography separation and purification, the purified (Z)-N-(5-(fluoromethyl / 1-fluoroalkyl / fluoro(aryl)methyl)-3-alkyl / substituted alkyl / aryl thiazolidine-2-ylidene)-alkyl / aryl formamides and (Z)-N-(6-(fluoromethyl / 1-fluoroalkyl-3-alkyl / substituted alkyl / aryl(fluoroethyl)-1,3-thiazolidine-2-ylidene)alkyl / aryl formamides are obtained.

[0026] The application further provides a kind of N-((2Z,5E)-5-(1-fluoroethylene / 1-fluoroalkyl / 1-fluoro substituted alkyl)-3-alkyl / substituted alkyl / aryl thiazolidine-2-ylidene) alkyl / aryl amide compound, which has the following formula (4) structure:

[0027]

[0028] Wherein,

[0029] R 7 It is alkyl, substituted alkyl or aryl;

[0030] R 8 It is hydrogen or alkyl;

[0031] R 9 It is alkyl or substituted alkyl;

[0032] R 10 It is alkyl, substituted alkyl or aryl;

[0033] The aryl group includes p-fluorophenyl, p-chlorophenyl, p-bromophenyl, p-iodophenyl, p-trifluoromethylphenyl, p-methoxyphenyl, p-esterylphenyl, o-fluorophenyl, m-fluorophenyl, and m-methoxyphenyl; the alkyl and substituted alkyl groups include benzyl, diphenylmethyl, 2-(2-thienyl)ethyl, 2-(phenyl)ethyl, 2-(phenoxy)ethyl, 4-N-Boc-piperidinyl, tert-butyl, cyclohexyl, methyl, n-butyl, and n-propyl.

[0034] This invention also proposes a method for synthesizing N-((2Z,5E)-5-(1-fluoroethylidene / 1-fluoroalkylidene / 1-fluorosubstituted alkylidene)-3-alkyl / substituted alkyl / arylthiazolyl-2-yl)alkyl / arylamide compounds, comprising: placing N-(high)propynyl-N-(alkyl / substituted alkyl / aryl)aminethioformyl)alkyl / arylamide, iodine(III) oxidant, and fluorine source in an organic solvent at room temperature, and subjecting them to a thiofluoroolefin bifunctionalization reaction to obtain the N-((2Z,5E)-5-(1-fluoroethylidene / 1-fluoroalkylidene / 1-fluorosubstituted alkylidene)-3-alkyl / substituted alkyl / arylthiazolyl-2-yl)alkyl / arylamide compounds; the process is shown in reaction formula (IⅠ):

[0035]

[0036] in,

[0037] R 7 R 8 R 9 R 10 The definition is the same as shown in equation (4).

[0038] Wherein, the molar ratio of N-(high)propyne-N-(alkyl / substituted alkyl / aryl)aminethiocarbamoyl)alkyl / aryl amide shown in formula (3) to iodine (III) oxidant is 1:(1-3); preferably, it is 1:1.05;

[0039] Wherein, the molar ratio of N-(high)propyne-N-(alkyl / substituted alkyl / aryl)aminethiocarbamoyl)alkyl / aryl amide shown in formula (3) to the fluorine source is 1:(1-20); preferably, it is 1:10.5.

[0040] The iodine (III) oxidant is PhI(OPiv)2, PhI(OAc)2, or PhI(OAd)2; preferably, it is PhI(OPiv)2.

[0041] The fluorine source is Et3N·3HF or py·8HF; preferably, it is Et3N·3HF.

[0042] The organic solvent is acetonitrile, dichloromethane, toluene, 1,4-dioxane, diethyl ether, tetrahydrofuran and methyl tert-butyl ether; preferably, 1,4-dioxane.

[0043] The reaction time is 1-8 hours; preferably, 3 hours.

[0044] The method further comprises post-treatment and column chromatography separation and purification steps; the separation and purification is column chromatography separation using petroleum ether / ethyl acetate or other mixed solvents as eluent.

[0045] In one specific embodiment, the method comprises: in an organic solvent, N-(high) propargyl-N-(alkyl / substituted alkyl / aryl) amine thioformyl) alkyl / aryl amide, iodine (III) oxidant and fluorine source, at room temperature, TLC monitoring to the reaction of raw material (3) is complete; the reaction system is quenched with saturated sodium bicarbonate solution, extracted with dichloromethane three times, the combined organic layer is washed with saturated brine, then the organic phase is concentrated under reduced pressure, the residue is separated by column chromatography with a certain proportion of eluent to obtain N-((2Z,5E)-5-(1-fluoroethyl / 1-fluoroalkyl / 1-fluoro-substituted alkyl)-3-alkyl / substituted alkyl / aryl thiazolidine-2-ylidene) alkyl / aryl amide compound as shown in formula (4).

[0046] The method for synthesizing N-((2Z,5E)-5-(1-fluoroethyl / 1-fluoroalkyl / 1-fluoro-substituted alkyl)-3-alkyl / substituted alkyl / aryl thiazolidine-2-ylidene) alkyl / aryl amide compound is to put N-(high) propargyl-N-(alkyl / substituted alkyl / aryl) amine thioformyl) alkyl / aryl amide, iodine (III) oxidant and fluorine source in an organic solvent, at room temperature, to occur sulfur fluoride olefin bifunctionalization reaction, to obtain the N-((2Z,5E)-5-(1-fluoroethyl / 1-fluoroalkyl / 1-fluoro-substituted alkyl)-3-alkyl / substituted alkyl / aryl thiazolidine-2-ylidene) alkyl / aryl amide compound; after post-treatment and column chromatography separation and purification, the purified N-((2Z,5E)-5-(1-fluoroethyl / 1-fluoroalkyl / 1-fluoro-substituted alkyl)-3-alkyl / substituted alkyl / aryl thiazolidine-2-ylidene) alkyl / aryl amide compound is obtained.

[0047] The application further provides a 5-(2-fluoroprop-2-yl / 2-fluoro-substituted alkyl / fluoromethyl / fluoro(aryl)methyl) thiazolidin-2-one compound and a 6-(2-fluoroprop-2-yl / 2-fluoro-substituted alkyl / fluoromethyl / fluoro(aryl)methyl)-1,3-thiazinan-2-one compound, which has the following formula (6):

[0048]

[0049] wherein,

[0050] R 11 is alkyl, substituted alkyl or aryl;

[0051] R 12 is hydrogen or alkyl;

[0052] R 13 is hydrogen, alkyl, substituted alkyl or aryl;

[0053] R 14 , R 15 are each independently hydrogen, alkyl, substituted alkyl or aryl;

[0054] wherein, the aryl includes p-fluorophenyl, p-chlorophenyl, p-bromophenyl, p-iodophenyl, p-trifluoromethylphenyl, p-methoxyphenyl, p-esterphenyl, o-fluorophenyl, m-fluorophenyl, m-methoxyphenyl; the alkyl and substituted alkyl include benzyl, diphenylmethyl, 2-(2-thienyl)ethyl, 2-(phenyl)ethyl, 2-(phenoxy)ethyl, 4-N-Boc-piperidinyl, t-butyl, cyclohexyl, methyl, n-butyl, n-propyl.

[0055] The present application also provides a synthesis method of 5-(2-fluoroprop-2-yl / 2-fluoro-substituted alkyl / fluoromethyl / fluoro(aryl)methyl)thiazolidine-2-one and 6-(2-fluoroprop-2-yl / 2-fluoro-substituted alkyl / fluoromethyl / fluoro(aryl)methyl)-1,3-thiazinane-2-one, comprising: reacting ((high)allyl)(phenyl)aminothiocarbonyl fluoride ((high)allyl)(alkyl / substituted alkyl / aryl)amine thioformyl fluoride, iodine (III) oxidant and fluorine source in an organic solvent at room temperature to generate the 5-(2-fluoroprop-2-yl / 2-fluoro-substituted alkyl / fluoromethyl / fluoro(aryl)methyl)thiazolidine-2-one and 6-(2-fluoroprop-2-yl / 2-fluoro-substituted alkyl / fluoromethyl / fluoro(aryl)methyl)-1,3-thiazinane-2-one after hydrolysis and sulfur-fluoro olefin bifunctionalization reaction; the process is shown in the following reaction formula (I II):

[0056]

[0057] wherein,

[0058] R 11 , R 12 , R 13 , R 14 , R 15 are the same as shown in formula (6).

[0059] wherein the molar ratio of ((h)allyl)(phenyl)aminothiocarbonyl fluoride ((h)allyl)(alkyl / substituted alkyl / aryl)amine thioformic fluoride of formula (5) to the iodine (III) oxidant is 1:(1-3); preferably, 1:2;

[0060] wherein the molar ratio of ((h)allyl)(phenyl)aminothiocarbonyl fluoride ((h)allyl)(alkyl / substituted alkyl / aryl)amine thioformic fluoride of formula (5) to the fluorine source is 1:(1-20); preferably, 1:9.

[0061] wherein the iodine (III) oxidant is PhI(OPiv)2, PhI(OAc)2, PhI(OAd)2; preferably, PhI(OPiv)2.

[0062] wherein the fluorine source is Et3N·3HF, py·8HF; preferably, Et3N·3HF.

[0063] wherein the organic solvent is acetonitrile, dichloromethane, toluene, 1,4-dioxane, diethyl ether, xylene, chlorobenzene and trifluorotoluene; preferably, toluene.

[0064] wherein the reaction time is 1-8 hours; preferably, 4 hours.

[0065] wherein the method further comprises post-treatment and column chromatography separation and purification steps; wherein the separation and purification is column chromatography separation using petroleum ether / ethyl acetate or other solvents as eluent.

[0066] In one specific embodiment, the method comprises: adding ((h)allyl)(phenyl)aminothiocarbonyl fluoride ((h)allyl)(alkyl / substituted alkyl / aryl)amine thioformic fluoride of formula (5), an iodine (III) oxidant and a fluorine source in an organic solvent, monitoring the reaction of raw material (5) to completion at room temperature by TLC; quenching the reaction system with saturated sodium bicarbonate solution, extracting with dichloromethane three times, washing the combined organic layer with saturated brine, then concentrating the organic phase under reduced pressure, and separating by column chromatography using a certain proportion of eluent to obtain 5-(2-fluoroprop-2-yl / 2-fluoro-substituted alkyl / fluoromethyl / fluoro(aryl)methyl)thiazolidine-2-ketone and 6-(2-fluoroprop-2-yl / 2-fluoro-substituted alkyl / fluoromethyl / fluoro(aryl)methyl)-1,3-thiazolidine-2-ketone compounds of formula (6).

[0067] The method for synthesizing 5-(2-fluoroprop-2-yl / 2-fluoro-substituted alkyl / fluoromethyl / fluoro(aryl)methyl))thiazolidine-2-ketone compounds and 6-(2-fluoroprop-2-yl / 2-fluoro-substituted alkyl / fluoromethyl / fluoro(aryl)methyl))-1,3-thiazine-2-ketone compounds provided by the application is that ((high) allyl)(phenyl) aminothiocarbonyl fluoride ((high) allyl)(alkyl / substituted alkyl / aryl) amine thioformyl fluoride, an iodine (III) oxidant and a fluorine source are in an organic solvent, and a sulfur-fluoro-olefin bifunctionalization reaction occurs at room temperature to obtain the 5-(2-fluoroprop-2-yl / 2-fluoro-substituted alkyl / fluoromethyl / fluoro(aryl)methyl))thiazolidine-2-ketone compounds and 6-(2-fluoroprop-2-yl / 2-fluoro-substituted alkyl / fluoromethyl / fluoro(aryl)methyl))-1,3-thiazine-2-ketone compounds; after post-treatment and column chromatography separation and purification, the purified 5-(2-fluoroprop-2-yl / 2-fluoro-substituted alkyl / fluoromethyl / fluoro(aryl)methyl))thiazolidine-2-ketone compounds and 6-(2-fluoroprop-2-yl / 2-fluoro-substituted alkyl / fluoromethyl / fluoro(aryl)methyl))-1,3-thiazine-2-ketone compounds are obtained.

[0068] The application also provides the use of the compounds shown in formula (2), formula (4) and formula (6) in the synthesis of other compounds (including but not limited to compounds 7-1, 8-1 and 9-1), pharmaceutical intermediates, or in the preparation of drugs with antitumor, antidepressant, antihypertensive, anti-inflammatory, anti-Alzheimer's disease, insecticidal activity, or as progesterone receptor binders in the preparation of drugs with antibacterial, antitumor, antioxidant, antipyretic activity, or as calcium channel modulators and cannabinoid receptor ligands in the preparation of drugs with anti-HIV, anticonvulsant, bactericidal, insecticidal activity, or as agonists of EP4, and as prostaglandin E2 receptor subtypes in the preparation of drugs for treating glaucoma metabolism, treating diabetes, treating fatty liver and the like.

[0069] The present application adopts raw materials which are easy to prepare and iodine (III) oxidizing agent and fluorine source which are easy to obtain to obtain the (Z)-N-(5-(fluoromethyl / 1-fluoroalkyl / fluoro(aryl)methyl)-3-alkyl / substituted alkyl / aryl thiazolidine-2-ylidene)-alkyl / aryl carboxamide compound, (Z)-N-(6-(fluoromethyl / 1-fluoroalkyl-3-alkyl / substituted alkyl / aryl(fluoroethyl)-1,3-thiazolidine-2-ylidene)alkyl / aryl carboxamide compound, N-((2Z,5E)-5-(1-fluoroethylene / 1-fluoroalkylene / 1-fluoro-substituted alkyl)-3-alkyl / substituted alkyl / aryl thiazolidine-2-ylidene)alkyl / aryl amide compound, 5-(2-fluoroprop-2-yl / 2-fluoro-substituted alkyl / fluoromethyl / fluoro(aryl)methyl))thiazolidine-2-ketone compound and 6-(2-fluoroprop-2-yl / 2-fluoro-substituted alkyl / fluoromethyl / fluoro(aryl)methyl))-1,3-thiazolidine-2-ketone compound through a sulfur-fluoro olefin bifunctionalization reaction. The method has the advantages of simple operation, mild conditions and wide substrate application range. The (Z)-N-(5-(fluoromethyl / 1-fluoroalkyl / fluoro(aryl)methyl)-3-alkyl / substituted alkyl / aryl thiazolidine-2-ylidene)-alkyl / aryl carboxamide compound, (Z)-N-(6-(fluoromethyl / 1-fluoroalkyl-3-alkyl / substituted alkyl / aryl(fluoroethyl)-1,3-thiazolidine-2-ylidene)alkyl / aryl carboxamide compound, N-((2Z,5E)-5-(1-fluoroethylene / 1-fluoroalkylene / 1-fluoro-substituted alkyl)-3-alkyl / substituted alkyl / aryl thiazolidine-2-ylidene)alkyl / aryl amide compound, 5-(2-fluoroprop-2-yl / 2-fluoro-substituted alkyl / fluoromethyl / fluoro(aryl)methyl))thiazolidine-2-ketone compound and 6-(2-fluoroprop-2-yl / 2-fluoro-substituted alkyl / fluoromethyl / fluoro(aryl)methyl))-1,3-thiazolidine-2-ketone compound synthesized by the present application are new compounds, which are synthesized for the first time and can be applied to the preparation of other compounds, pharmaceutical intermediates, and applied to chemical pharmacy, biological pharmacy and special preparations. For example, other compounds synthesized by using the above compounds include but are not limited to 7-1, 8-1, 9-1; the specific synthesis process and characterization are shown in specific examples 70-72. DETAILED DESCRIPTION

[0070] The present application will be further described in detail below in combination with specific examples, and the protection scope of the present application is not limited to the following examples. Changes and advantages that can be thought of by those skilled in the art without departing from the spirit and scope of the present application are included in the present application, and the appended claims are the protection scope.

[0071] Example 1

[0072]

[0073] To the reaction tube was added PhI(OPiv)2(92.5 mg, 0.23 mmol), 3 mL of toluene and Et3N-3HF (96.7 mg, 0.6 mmol), after stirring for 5 minutes, N-[allyl(phenyl)aminothioformyl]benzamide (59.3 mg, 0.2 mmol) was added, and the reaction was carried out at room temperature for 2 hours, TLC monitoring of the starting material N-[allyl(phenyl)aminothioformyl]benzamide was completely consumed, the reaction system was quenched with saturated sodium bicarbonate solution, extracted with dichloromethane three times, the combined organic layer was washed with saturated brine, and then concentrated under reduced pressure, the residue was separated by column chromatography with a certain proportion of eluent to obtain 53.9 mg of pure product, the structure of which is shown in formula (2-1). The yield was 86%. (1、. When the molar ratio of N-[allyl(phenyl)aminothioformyl]benzamide to PhI(OPiv)2 is 2, and the other conditions are the same as above, the yield is 85%; 2、When the molar ratio of N-[allyl(phenyl)aminothioformyl]benzamide to PhI(OPiv)2 is 3, and the other conditions are the same as above, the yield is 85%; 3、When the molar ratio of N-[allyl(phenyl)aminothioformyl]benzamide to PhI(OPiv)2 is 1, and the other conditions are the same as above, the yield is 75%; 4、When the molar ratio of N-[allyl(phenyl)aminothioformyl]benzamide to fluorine source is 1:20, and the other conditions are the same as above, the yield is 86%; 5、When the molar ratio of N-[allyl(phenyl)aminothioformyl]benzamide to fluorine source is 1:1, and the other conditions are the same as above, the yield is 15%; 6、When the oxidant is PhI(OAc)2, and the other conditions are the same as above, the yield is 75%; 7、When the oxidant is PhI(OAd)2, and the other conditions are the same as above, the yield is 86%; When the fluorine source is py-8HF, and the other conditions are the same as above, the yield is 4%; 8、When the organic solvent is acetonitrile, and the other conditions are the same as above, the yield is 69%; 9、When the organic solvent is dichloromethane, and the other conditions are the same as above, the yield is 47%; 9、When the organic solvent is 1,4-dioxane, and the other conditions are the same as above, the yield is 70%; 9、When the organic solvent is diethyl ether, and the other conditions are the same as above, the yield is 72%; 10、When the solvent is xylene, and the other conditions are the same as above, the yield is 79%; 11、When the solvent is chlorobenzene, and the other conditions are the same as above, the yield is 72%; 12、When the solvent is trifluorotoluene, and the other conditions are the same as above, the yield is 81%; 13、When the reaction time is 1 hour, and the other conditions are the same as above, the yield is 56%; 14、When the reaction time is 4 hours, and the other conditions are the same as above, the yield is 84%; 15、When the reaction time is 8 hours, and the other conditions are the same as above, the yield is 83%.). 1 H NMR、 13 C NMR、 19 F NMR spectrum is shown in Figure 1, product:1 H NMR (600 MHz, CDC13) δ 8.26 - 8.01 (m, 2H), 7.65 - 7.43 (m, 5H), 7.35 (dt, J = 16.3, 7.4 Hz, 3H), 4.59 (dd, J = 9.6, 4.7 Hz, 0.5H), 4.51 (m, 1H), 4.43 (t, J = 9.7 Hz, 0.5H), 4.28 (dd, J = 11.1, 6.9 Hz, 1H), 4.18 (dd, J = 11.1, 2.4 Hz, 1H), 3.88 (m, 1H). 13 C NMR (151 MHz, CDC13) δ 176.2, 169.1, 140.1, 136.0, 132.2, 129.8, 129.0, 128.1, 126.9, 124.7, 82.2 (d, J = 178.9 Hz), 53.4 (d, J = 3.0 Hz), 40.2 (d, J = 21.0 Hz). 19 F NMR (565 MHz, CDC13) δ -211.77. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 17 H 15 FN2NaOS337.0781, found 337.0774.

[0074] Example 2

[0075]

[0076] The experimental method of this example is basically the same as that of Example 1. The raw material used in this example is (N-[allyl(4-fluorophenyl)aminothiocarbamoyl]benzamide, and the reaction is carried out at room temperature for 2 hours. The obtained product is shown in the structural formula (2-2). The yield is 78%. The nuclear magnetic resonance 1 H NMR、 13 C NMR、 19 F NMR spectrum is shown in Figure 2, and the product: 1 H NMR (500 MHz, CDC13) δ 8.14 - 8.04 (m, 2H), 7.47 (m, 3H), 7.37 (dd, J = 8.3, 7.0 Hz, 2H), 7.23 - 7.13 (m, 2H), 4.55 - 4.47 (m, 0.5H), 4.41 (t, J = 9.6 Hz, 1H), 4.23 (dd, J = 11.1, 6.9 Hz, 0.5H), 4.12 (dd, J = 11.1, 2.5 Hz, 1H), 3.88 (m, 1H). 13C NMR (151 MHz, CDCI3) δ 176.1, 169.3, 160.9 (d, J = 247.5 Hz), 136.0, 135.9, 132.3, 129.7, 128.1, 126.6 (d, J = 8.1 Hz), 115.9 (d, J = 22.8 Hz), 82.2 (d, J = 179.0 Hz), 53.4 (d, J = 3.0 Hz), 40.3 (d, J = 20.8 Hz). 19 F NMR (565 MHz, CDCI3) δ -1 14.00, -212.24. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 17 H 14 F2N2NaOS 355.0687, found 355.0676.

[0077] Example 3

[0078]

[0079] The experimental method of this example is basically the same as that of Example 1. The raw material used in this example is (N-[allyl(4-chlorophenyl)aminothiocarbamoyl]benzamide. The reaction is carried out at room temperature for 2 hours. The product obtained is shown in the structural formula (2-3). The yield is 74%. The nuclear magnetic resonance 1 H NMR、 13 C NMR、 19 F NMR spectrum is shown in Figure 3. The product: 1 H NMR (500 MHz, CDCI3) δ 8.16 - 8.04 (m, 2H), 7.53 - 7.42 (m, 5H), 7.38 (dd, J = 8.4, 7.0 Hz, 2H), 4.58 (dd, J = 9.6, 4.7 Hz, 0.5H), 4.55 - 4.45 (m, 1H), 4.40 (t, J = 9.6 Hz, 0.5H), 4.23 (dd, J = 1 1.1, 7.0 Hz, 1H), 4.1 1 (dd, J = 1 1.0, 2.6 Hz, 1H), 3.87 (m, 1H). 13 C NMR (126 MHz, CDCI3) δ 176.1, 169.1, 138.5, 135.8, 132.4, 132.1, 129.7, 129.0, 128.1, 125.8, 82.1 (d, J = 179.3 Hz), 53.1 (d, J = 3.1 Hz), 40.2 (d, J = 21.0 Hz). 19F NMR (565 MHz, CDCI3) δ -212.26. HRMS (ESI-TOF) m / z: [M + Na] 355.0687, found 355.0676. + calculated for C 17 H 14 F2N2NaOS 355.0687, found355.0676.

[0080] Example 4

[0081]

[0082] The experimental method of this example is basically the same as that of Example 1. The raw material used in this example is (N-[allyl(4-bromophenyl)aminothioformyl]benzamide. The reaction is carried out at room temperature for 2 hours. The obtained product is shown in the structural formula (2-4). The yield is 72%. The nuclear magnetic resonance 1 H NMR、 13 C NMR、 19 F NMR spectrum is shown in Figure 4. The product: 1 H NMR (500 MHz, CDCI3) δ 8.10 (dd, J = 8.3, 1.4 Hz, 2H), 7.60 (d, J = 8.7 Hz, 2H), 7.53 - 7.45 (m, 1H), 7.45 - 7.33 (m, 4H), 4.59 (dd, J = 9.6, 4.7 Hz, 0.5H), 4.49 (m, 1H), 4.40 (t, J = 9.6 Hz, 0.5H), 4.24 (dd, J = 11.0, 7.0 Hz, 1H), 4.12 (dd, J = 11.0, 2.5 Hz, 1H), 3.87 (m, 1H). 13 C NMR (126 MHz, CDCI3) δ 176.1, 169.1, 139.1, 135.8, 132.4, 132.0, 129.8, 128.14126.1, 120.0, 82.1 (d, J = 179.2 Hz), 53.0 (d, J = 3.0 Hz), 40.2 (d, J = 20.9 Hz). 19 F NMR (565 MHz, CDCI3) δ -212.17. HRMS (ESI-TOF) m / z: [M + Na] 355.0687, found 355.0676. + calculated for C 17 H 14 BrFN2NaOS 414.9886, found414.9883.

[0083] Example 5

[0084]

[0085] The experimental method of this example is basically the same as that of Example 1. The raw material used in this example is (N-[allyl(4-iodophenyl)aminothiocarbamoyl]benzamide, and the reaction is carried out at room temperature for 2 hours. The obtained product is shown in structural formula (2-5). The yield is 85%. The nuclear magnetic resonance 1 H NMR, 13 C NMR, 19 The F NMR spectrum is shown in Figure 5, and the product: 1 H NMR (500 MHz, CDC13) δ 8.10 (dd, J = 8.3, 1.4 Hz, 2H), 7.83 - 7.74 (m, 2H), 7.52 - 7.45 (m, 1H), 7.43 - 7.35 (m, 2H), 7.35 - 7.26 (m, 2H), 4.57 (dd, J = 9.6, 4.7 Hz, 0.5H), 4.48 (m, 1H), 4.38 (t, J = 9.6 Hz, 0.5H), 4.22 (dd, J = 11.0, 7.0 Hz, 1H), 4.10 (dd, J = 11.0, 2.6 Hz, 1H), 3.92 - 3.80 (m, 1H). 13 CNMR (151 MHz, CDC13) δ 176.1, 169.0, 139.7, 137.9, 135.7, 132.4, 129.7, 128.1, 126.2, 91.1, 82.1 (d, J = 179.2 Hz), 52.9 (d, J = 3.0 Hz), 40.2 (d, J = 21.0 Hz). 19 F NMR (565 MHz, CDC13) δ -212.19. HRMS (ESI-TOF) m / z: [M+Na] + calculated for C 17 H 14 IFN2NaOS 462.9748, found 462.9760.

[0086] Example 6

[0087]

[0088] The experimental method of this example is basically the same as that of Example 1. The raw material used in this example is (N-[allyl(4-iodophenyl)aminothiocarbamoyl]benzamide, and the reaction is carried out at room temperature for 2 hours. The obtained product is shown in structural formula (2-5). The yield is 85%. The nuclear magnetic resonance 1 H NMR, 13 C NMR, 19 The F NMR spectrum is shown in Figure 6, and the product: 1H NMR (500 MHz, CDC13) δ 8.17 - 8.07 (m, 2H), 7.80 - 7.66 (m, 4H), 7.54 - 7.46 (m, 1H), 7.40 (dd, J = 8.3, 7.0 Hz, 2H), 4.59 (dd, J = 9.6, 4.7 Hz, 0.5H), 4.50 (m, 1H), 4.40 (t, J = 9.6 Hz, 0.5H), 4.30 (dd, J = 10.9, 6.9 Hz, 1H), 4.17 (dd, J = 10.9, 2.6 Hz, 1H), 3.89 (m, Hz, 1H). 13 C NMR (126 MHz, CDC13) δ 176.2, 169.3, 143.0, 135.6, 132.6, 129.8, 128.2 (q, J = 32.8 Hz), 128.2, 126.0 (q, J = 3.7 Hz), 123.8 (q, J = 272.2 Hz), 124.3, 82.1 (d, J = 179.4 Hz), 52.8 (d, J = 3.1 Hz), 40.2 (d, J = 21.0 Hz). 19 F NMR (565 MHz, CDC13) δ -62.31, -212.45. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 18 H 14 F4N2NaOS 405.0655, found 405.0653.

[0089] Example 7

[0090]

[0091] The experimental method of this example is basically the same as that of Example 1. The raw material used in this example is (N-[allyl(4-methoxyphenyl)aminothiocarbamoyl]benzamide. The reaction is carried out at room temperature for 2 hours. The obtained product is shown in the structural formula (2-7). The yield is 33%. The nuclear magnetic resonance 1 H NMR, 13 C NMR, 19 The F NMR spectrum is shown in Figure 7. The product: 1H NMR (500 MHz, CDC13) δ 8.10 (dd, J = 8.3, 1.4 Hz, 2H), 7.83 - 7.74 (m, 2H), 7.52 - 7.45 (m, 1H), 7.43 - 7.35 (m, 2H), 7.35 - 7.26 (m, 2H), 4.57 (dd, J = 9.6, 4.7 Hz, 0.5H), 4.48 (m, 1H), 4.38 (t, J = 9.6 Hz, 0.5H), 4.22 (dd, J = 11.0, 7.0 Hz, 1H), 4.10 (dd, J = 11.0, 2.6 Hz, 1H), 3.92 - 3.80 (m, 1H). 13 C NMR (151 MHz, CDC13) δ 176.1, 169.0, 139.7, 137.9, 135.7, 132.4, 129.7, 128.1, 126.2, 91.1, 82.1 (d, J = 179.2 Hz), 52.9 (d, J = 3.0 Hz), 40.2 (d, J = 21.0 Hz). 19 F NMR (565 MHz, CDC13) δ -212.19. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 17 H 14 IFN2NaOS462.9748, found 462.9760.

[0092] Example 8

[0093]

[0094] The experimental method of this example is basically the same as that of Example 1. The raw material used in this example is (N-[allyl(2-fluorophenyl)aminothiocarbamoyl]benzamide. The reaction is carried out at room temperature for 2 hours. The product obtained is shown in the structural formula (2-8). The yield is 72%. The nuclear magnetic resonance 1 H NMR、 13 C NMR、 19 The F NMR spectrum is shown in Figure 8. The product: 1 H NMR (500 MHz, CDC13) δ 8.03 (dd, J = 8.3, 1.4 Hz, 2H), 7.53 - 7.36 (m, 3H), 7.36 - 7.21 (m, 4H), 4.62 - 4.54 (m, 1H), 4.53 - 4.44 (m, 1H), 4.18 (dd, J = 11.1, 6.9 Hz, 1H), 4.08 (dd, J = 11.1, 2.2 Hz, 1H), 3.92 (m, 1H). 13C NMR (151 MHz, CDCI3) δ 176.2, 169.9, 157.3 (d, J = 251.3 Hz), 135.8, 132.2, 129.8, 129.6 (d, J = 7.8 Hz), 128.8, 128.0, 127.4 (d, J = 11.8 Hz), 124.5 (d, J = 3.7 Hz), 116.8 (d, J = 19.9 Hz), 82.1 (d, J = 179.0 Hz), 52.6 (t, J = 2.9 Hz), 41.2 (d, J = 21.1 Hz). 19 F NMR (565 MHz, CDCI3) δ -119.45, -211.73. HRMS (ESI-TOF) m / z: [M + Na] + C 17 H 14 F2N2NaOS 355.0687, found 355.0682.

[0095] Example 9

[0096]

[0097] The experimental method of this example is basically the same as that of Example 1. The raw material used in this example is (N-[allyl(3-fluorophenyl)aminothiocarbamoyl]benzamide. The reaction is carried out at room temperature for 2 hours. The product obtained is shown in structural formula (2-9). The yield is 86%. The nuclear magnetic resonance 1 H NMR、 13 C NMR、 19 The F NMR spectrum is shown in Figure 9. The product: 1 H NMR (500 MHz, CDCI3) δ 8.18 - 8.09 (m, 2H), 7.54 - 7.35 (m, 5H), 7.30 (dd, J = 8.2, 2.1 Hz, 1H), 7.04 (td, J = 8.2, 2.5 Hz, 1H), 4.59 (dd, J = 9.6, 4.7 Hz, 0.5H), 4.50 (m, 1H), 4.40 (t, J = 9.6 Hz, 0.5H), 4.26 (dd, J = 11.0, 6.9 Hz, 1H), 4.16 (dd, J = 11.0, 2.5 Hz, 1H), 3.88 (m, Hz, 1H). 13C NMR (151 MHz, CDCI3) δ 176.20, 169.10, 162.62 (d, J = 246.8 Hz), 141.36 (d, J = 10.0 Hz), 135.77, 132.43, 130.03 (d, J = 9.2 Hz), 129.79, 128.16, 119.64 (d, J = 3.2 Hz), 113.61 (d, J = 21.1 Hz), 112.20 (d, J = 24.9 Hz), 82.11 (d, J = 179.3 Hz), 53.10 (d, J = 3.0 Hz), 40.15 (d, J = 20.9 Hz). 19 F NMR (565 MHz, CDCI3) δ -111.16, -212.12. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 17 H 14 F2N2NaOS 355.0687, found 355.0677.

[0098] Example 10

[0099]

[0100] The experimental method of this example is basically the same as that of Example 1. The raw material used in this example is (N-[allyl(methyl)aminothioformyl]benzamide. The reaction is carried out at room temperature for 2 hours. The product obtained is shown in structural formula (2-10). The yield is 62%. The nuclear magnetic resonance 1 H NMR、 13 C NMR、 19 The F NMR spectrum is shown in Figure 10. The product: 1 H NMR (500 MHz, CDCI3) δ 8.34 - 8.27 (m, 2H), 7.55 - 7.47 (m, 1H), 7.43 (dd, J = 8.3, 6.8 Hz, 2H), 7.40 - 7.30 (m, 5H), 5.06 - 4.94 (m, 2H), 4.41 (m, 1H), 4.25 (dt, J = 47.6, 9.6 Hz, 1H), 3.75 (m, 1H), 3.70 - 3.60 (m, 2H). 13 C NMR (151 MHz, CDCI3) δ 176.20, 169.10, 162.62 (d, J = 246.8 Hz), 141.36 (d, J = 10.0 Hz), 135.77, 132.43, 130.03 (d, J = 9.2 Hz), 129.79, 128.16, 119.64 (d, J = 3.2 Hz), 113.61 (d, J = 21.1 Hz), 112.20 (d, J = 24.9 Hz), 82.11 (d, J = 179.3 Hz), 53.10 (d, J = 3.0 Hz), 40.15 (d, J = 20.9 Hz). 19F NMR (565 MHz, CDCI3) δ -212.12. HRMS (ESI-TOF) m / z: [M + Na] 351.0938, found 351.0935. + calculated for C 18 H 17 FN2NaOS 351.0938, found 351.0935.

[0101] Example 11

[0102]

[0103] The experimental method of this example is basically the same as that of Example 1. The raw material used in this example is (N-[allyl(diphenylmethyl)aminothiocarbamoyl]benzamide. The reaction is carried out at room temperature for 2 hours. The obtained product is shown in the structural formula (2-11). The yield is 65%. The nuclear magnetic resonance spectrum is as follows: 1 H NMR, 13 C NMR, 19 The F NMR spectrum is shown in Figure 11. The product: 1 H NMR (500 MHz, CDCI3) δ 8.30 - 8.15 (m, 2H), 7.52 - 7.45 (m, 1H), 7.44 - 7.26 (m, 13H), 4.48 (dd, J = 9.6, 4.9 Hz, 0.5H), 4.44 - 4.32 (m, 1H), 4.26 (t, J = 9.6 Hz, 0.5H), 3.73 (m, 1H), 3.63 (dd, J = 11.5, 2.9 Hz, 1H), 3.54 (dd, J = 11.6, 7.4 Hz, 1H). 13 C NMR (126 MHz, CDCI3) δ 176.0, 170.3, 137.8, 137.0, 136.2, 132.1, 129.7, 129.0, 128.8, 128.8, 128.2, 128.1, 128.0, 128.0, 82.4 (d, J = 179.0 Hz), 63.5, 48.0 (d, J = 2.9 Hz), 40.3 (d, J = 21.0 Hz). 19 F NMR (565 MHz, CDCI3) δ -212.12. HRMS (ESI-TOF) m / z: [M + Na] 351.0938, found 351.0935. + calculated for C 24 H 21 FN2NaOS 427.1251, found427.1253.

[0104] Example 12

[0105]

[0106] The experimental method of this example is basically the same as that of Example 1. The raw material used in this example is (N-[(2-phenyl)ethyl]thiocarbamoyl)benzamide. The reaction is carried out at room temperature for 2 hours. The obtained product is shown in structural formula (2-13). The yield is 70%. Nuclear magnetic resonance 1 H NMR, 13 C NMR, 19 The F NMR spectrum is shown in Figure 12. The product: 1 H NMR (500 MHz, CDC13) δ 8.35 - 8.23 (m, 2H), 7.56 - 7.47 (m, 1H), 7.44 (dd, J = 8.2, 6.8 Hz, 2H), 7.19 (dd, J = 5.1, 1.2 Hz, 1H), 6.95 (dd, J = 5.2, 3.4 Hz, 1H), 6.89 (dd, J = 3.4, 1.2 Hz, 1H), 4.34 (m, 1H), 4.22 - 4.04 (m, 2H), 3.93 (dt, J = 13.7, 6.9 Hz, 1H), 3.74 - 3.65 (m, 1H), 3.65 - 3.59 (m, 2H), 3.31 (td, J = 7.1, 4.8 Hz, 2H). 13 C NMR (151 MHz, CDC13) δ 175.8, 169.5, 140.4, 136.3, 132.1, 129.7, 128.1, 127.2, 125.8, 124.4, 82.4 (d, J = 178.7 Hz), 51.6 (d, J = 3.0 Hz), 49.5, 40.5 (d, J = 21.0 Hz), 27.6. 19 F NMR (565 MHz, CDC13) δ -212.5. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 17 H 17 FN2NaOS2371.0659, found 371.0648.

[0107] Example 13

[0108]

[0109] The experimental method of this example is basically the same as that of Example 1. The raw material used in this example is (N-[(2-phenyl)ethyl]thiocarbamoyl)benzamide. The reaction is carried out at room temperature for 2 hours. The obtained product is shown in structural formula (2-13). The yield is 70%. Nuclear magnetic resonance 1 H NMR, 13 C NMR,19 The F NMR spectrum is shown in Figure 13, and the product is: 1 H NMR (600 MHz, CDC13) δ 8.35 - 8.24 (m, 2H), 7.52 (td, J = 7.1, 1.4 Hz, 1H), 7.49 - 7.41 (m, 2H), 7.33 (t, J = 7.6 Hz, 2H), 7.29 - 7.19 (m, 3H), 4.31 (m, 1H), 4.15 - 3.99 (m, 2H), 3.91 (m, 1H), 3.72 - 3.62 (m, 1H), 3.62 - 3.49 (m, 2H), 3.08 (dq, J = 13.4, 6.3 Hz, 2H). 13 C NMR (151 MHz, CDC13) δ 175.8, 169.4, 138.1, 136.4, 132.0, 129.6, 128.8, 128.0, 126.8, 82.3 (d, J = 178.6 Hz), 51.5 (d, J = 2.9 Hz), 49.2, 40.3 (d, J = 20.9 Hz), 33.4. 19 F NMR (565 MHz, CDC13) δ -211.44. HRMS (ESI-TOF) m / z: [M + H] + calculated for C 19 H 20 FN2OS 343.1275, found 343.1254.

[0110] Example 14

[0111]

[0112] The experimental method of this example is basically the same as that of Example 1. The raw material used in this example is (N- [allyl (2-phenoxy) ethyl) aminothiocarbamoyl] benzamide. The reaction is carried out at room temperature for 2 hours. The product obtained is shown in structural formula (2-14). The yield is 83%. The nuclear magnetic resonance 1 H NMR、 13 C NMR、 19 The F NMR spectrum is shown in Figure 14, and the product is: 1H NMR (500 MHz, CDC13) δ 8.24 (d, J = 7.6 Hz, 2H), 7.50 (t, J = 7.3 Hz, 1H), 7.42 (t, J = 7.5 Hz, 2H), 7.29 (t, J = 7.7 Hz, 2H), 6.97 (t, J = 7.4 Hz, 1H), 6.91 (d, J = 8.0 Hz, 2H), 4.48 - 4.16 (m, 5H), 4.13 - 4.01 (m, 2H), 3.98 (dd, J = 11.5, 7.1 Hz, 1H), 3.77 (m, 1H). 13 C NMR (151 MHz, CDC13) δ 175.8, 169.7, 158.1, 136.3, 132.1, 129.7, 129.7, 128.1, 121.4, 114.4, 82.3 (d, J = 178.7 Hz), 65.7, 52.7 (d, J = 2.8 Hz), 47.3, 40.8 (d, J = 21.0 Hz). 19 F NMR (565 MHz, CDC13) δ -211.5. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 19 H 19 FN2NaO2S 381.1043, found 381.1047.

[0113] Example 15

[0114]

[0115] The experimental method of this example is basically the same as that of Example 1. The starting material used in this example is tert-butyl 4-(1-allyl-3-benzoylthio ureido) piperidine-1-carboxylate. The reaction is carried out at room temperature for 2 hours. The obtained product is shown in structural formula (2-15). The yield is 66%. The nuclear magnetic resonance 1 H NMR, 13 C NMR, 19 The F NMR spectrum is shown in Figure 15. The product: 1 H NMR (600 MHz, CDC13) δ 8.28 - 8.19 (m, 2H), 7.54 - 7.48 (m, 1H), 7.43 (td, J = 7.6, 1.8 Hz, 2H), 4.81 (td, J = 12.2, 4.5 Hz, 1H), 4.44 (m, 1H), 4.37 - 4.15 (m, 3H), 3.86 - 3.60 (m, 3H), 2.89 (s, 2H), 1.88 (d, J = 10.8 Hz, 2H), 1.66 (s, 2H), 1.49 (s, 9H). 13C NMR (151MHz, CDCl3) δ175.9,169.5,154.6,136.3,132.1,129.6,128.1,82.2( d,J=178.6Hz),80.0,54.9,46.8,40.2(d,J=20.6Hz),29.4,28.7,28.4,27.2. 19 F NMR(565MHz,CDCl3)δ-212.04.HRMS(ESI-TOF)m / z:[M+Na] + Calculated for C 21 H 28 FN3NaO3S 444.1728,found444.1724.

[0116] Example 16

[0117]

[0118] The experimental method in this embodiment is basically the same as that in Example 1. The raw material used in this embodiment is (N-[allyl(phenyl)ethyl)aminothioformyl]-4-methoxybenzamide. The reaction is carried out at room temperature for 2 hours, and the product obtained is shown in structural formula (2-16). The yield is 74%. Nuclear magnetic resonance (NMR) 1 H NMR, 13 C NMR, 19 The F NMR spectrum is shown in Figure 16. Products: 1 HNMR (500MHz, CDCl3) δ8.13–8.02(m,2H),7.57–7.44(m,4H),7.33(tt,J=7.1,1.5Hz,1H),6.92–6.79(m,2H),4.59(dd,J=9.6,4. 8Hz,0.5H),4.54–4.45(m,1H),4.42(t,J=9.7Hz,0.5H),4.27(dd,J=11.1,6.9Hz,1H),4.16(dd,J=11.0,2.4Hz,1H),3.83(m,4H). 13 C NMR (151MHz, CDCl3) δ175.6,168.4,163.0,140.2,131.9,128.9,128.8,126.7,1 24.6, 113.3, 82.2 (d, J = 179.0Hz), 55.3, 53.2 (d, J = 3.0Hz), 40.2 (d, J = 20.9Hz). 19 F NMR(565MHz,CDCl3)δ-211.55.HRMS(ESI-TOF)m / z:[M+Na]+ Calculated for C 18 H 17 FN2NaO2S 367.0887, found 367.0877.

[0119] Example 17

[0120]

[0121] The experimental method of this example is basically the same as that of Example 1. The raw material used in this example is (N-[(allyl(phenyl)ethyl)aminothiocarbamoyl]-4- fluorobenzamide. The reaction is carried out at room temperature for 2 hours. The product obtained is shown in the structural formula (2-17). The yield is 86%. The nuclear magnetic resonance 1 H NMR、 13 C NMR、 19 F NMR spectrum is shown in Figure 17. The product: 1 HNMR (600 MHz, CDCl3) δ 8.28-8.19 (m, 2H), 7.54-7.48 (m, 1H), 7.43 (td, J = 7.6, 1.8 Hz, 2H), 4.81 (td, J = 12.2, 4.5 Hz, 1H), 4.44 (m, 1H), 4.37-4.15 (m, 3H), 3.86-3.60 (m, 3H), 2.89 (s, 2H), 1.88 (d, J = 10.8 Hz, 2H), 1.66 (s, 2H), 1.49 (s, 9H). 13 C NMR (151 MHz, CDCl3) δ 175.1, 169.2, 165.4 (d, J = 252.5 Hz), 140.0, 132.3 (d, J = 2.9 Hz), 132.2 (d, J = 9.2 Hz), 129.0, 127.0, 124.7, 115.0 (d, J = 21.7 Hz), 82.2 (d, J = 178.8 Hz), 53.4 (d, J = 3.0 Hz), 40.3 (d, J = 20.9 Hz). 19 FNMR (565 MHz, CDCl3) δ -107.28, -212.04. HRMS (ESI-TOF) m / z: [M+Na] + Calculated for C 17 H 14 F2N2NaOS 355.0687, found 355.0675.

[0122] Example 18

[0123]

[0124] The experimental method of this example is basically the same as that of Example 1. The raw material used in this example is (N-[(allyl(phenyl)ethyl)aminothiocarbamoyl]-4- chlorobenzamide. The reaction is carried out at room temperature for 2 hours. The obtained product is shown in structural formula (2-18). The yield is 80%. The nuclear magnetic resonance 1 H NMR, 13 C NMR, 19 The F NMR spectrum is shown in Figure 18. The product: 1 H NMR (500 MHz, CDC13) δ 8.02 (d, J = 8.1 Hz, 2H), 7.49 (d, J = 4.2 Hz, 4H), 7.33 (t, J = 6.6 Hz, 3H), 4.58 (dd, J = 9.6, 4.8 Hz, 0.5H), 4.55 - 4.45 (m, 1H), 4.42 (t, J = 9.6 Hz, 0.5H), 4.27 (dd, J = 11.3, 7.0 Hz, 1H), 4.15 (dt, J = 11.3, 1.9 Hz, 1H), 3.95 - 3.81 (m, 1H). 13 C NMR (151 MHz, CDC13) δ 175.1, 169.4, 139.9, 138.4, 134.5, 131.1, 129.0, 128.3, 127.0, 124.6, 82.1 (d, J = 179.2 Hz), 53.4 (d, J = 3.1 Hz), 40.3 (d, J = 21.0 Hz). 19 F NMR (565 MHz, CDC13) δ -212.25. HRMS (ESI-TOF) m / z: [M+Na] + calculated for C 17 H 14 ClFN2NaOS 371.0392, found 371.0370.

[0125] Example 19

[0126]

[0127] The experimental method of this example is basically the same as that of Example 1. The raw material used in this example is (N-[(allyl(phenyl)ethyl)aminothiocarbamoyl]-4- chlorobenzamide. The reaction is carried out at room temperature for 2 hours. The obtained product is shown in structural formula (2-18). The yield is 80%. The nuclear magnetic resonance 1 H NMR, 13 C NMR, 19 The F NMR spectrum is shown in Figure 19. The product: 1H NMR (500 MHz, CDC13) δ 7.95 (d, J = 8.3 Hz, 2H), 7.56 - 7.42 (m, 6H), 7.34 (d h, J = 8.7, 4.5 Hz, 1H), 4.59 (dd, J = 9.6, 4.8 Hz, 0.5H), 4.55 - 4.46 (m, 1H), 4.42 (t, J = 9.6 Hz, 0.5H), 4.27 (dd, J = 11.2, 7.0 Hz, 1H), 4.16 (dd, J = 11.2, 2.5 Hz, 1H), 3.88 (m, 1H). 13 CNMR (151 MHz, CDC13) δ 175.3, 169.5, 139.9, 135.0, 131.3, 131.3, 129.0, 127.2, 127.0, 124.7, 82.1 (d, J = 179.0 Hz), 53.4 (d, J = 3.0 Hz), 40.3 (d, J = 20.8 Hz). 19 F NMR (565 MHz, CDC13) δ -212.2. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 17 H 14 BrFN2NaOS 414.9886, found 414.9887.

[0128] Example 20

[0129]

[0130] The experimental method of this example is basically the same as that of Example 1. The raw material used in this example is (N-[(allyl (phenyl) ethyl) aminothiocarbamoyl]-4-iodobenzamide, and the reaction is carried out at room temperature for 2 hours. The obtained product is shown in the structural formula (2-20). The yield is 84%. The nuclear magnetic resonance 1 H NMR, 13 C NMR, 19 The F NMR spectrum is shown in Figure 20, and the product: 1 H NMR (500 MHz, CDC13) δ 7.87 - 7.76 (m, 2H), 7.76 - 7.65 (m, 2H), 7.56 - 7.41 (m, 4H), 7.34 (m, 1H), 4.60 (dd, J = 9.6, 4.7 Hz, 0.5H), 4.56 - 4.47 (m, 1H), 4.42 (t, J = 9.6 Hz, 0.5H), 4.28 (dd, J = 11.2, 7.0 Hz, 1H), 4.17 (dd, J = 11.2, 2.5 Hz, 1H), 3.89 (m, 1H). 13CNMR (151MHz, CDCl3) δ175.5, 169.5, 137.4, 135.6, 131.3, 129.0, 127.1, 124.7, 100.0, 82.2 (d, J = 178.8Hz), 53.5 (d, J = 1.5Hz), 40.3 (d, J = 20.7Hz). 19 F NMR(565MHz,CDCl3)δ-212.14.HRMS(ESI-TOF)m / z:[M+Na] + Calculated for C 17 H 14 IFN2NaOS 462.9748,found462.9758.

[0131] Example 21

[0132]

[0133] The experimental method in this embodiment is basically the same as that in Example 1. The raw material used in this embodiment is (N-[allyl(phenyl)ethyl)aminothioformyl]-4-methoxycarbonylbenzamide. The reaction is carried out at room temperature for 2 hours, and the product obtained is shown in structural formula (2-21). The yield is 79%. Nuclear magnetic resonance (NMR) 1 H NMR, 13 C NMR, 19 The F NMR spectrum is shown in Figure 21. Products: 1 HNMR (500MHz, CDCl3) δ8.20–8.11(m,2H),8.08–7.99(m,2H),7.51(d,J=5.5Hz,4H),7.36(tt,J=5.8,2.9Hz,1H),4.61(dd,J=9.6,4 .8Hz,0.5H),4.58–4.48(m,1H),4.44(t,J=9.7Hz,0.5H),4.31(dd,J=11.2,7.0Hz,1H),4.19(dd,J=11.3,2.5Hz,1H),3.91(m,4H). 13 C NMR (151MHz, CDCl3) δ175.4,169.8,166.7,139.9,139.9,133.0,129.6,129.3,129. 1,127.2,124.7,82.2(d,J=179.3Hz),53.5(d,J=2.9Hz),52.2,40.3(d,J=21.1Hz). 19 F NMR(565MHz,CDCl3)δ-212.29.HRMS(ESI-TOF)m / z:[M+Na]+ calculated for C 19 H 17 FN2NaO3S395.0836,found395.0830.

[0134] Example 22

[0135]

[0136] The experimental method of this example is basically the same as that of Example 1. The raw material used in this example is (N-[(2- chlorophenyl)ethyl]aminothiocarbamoyl]-2-fluorobenzamide. The reaction is carried out at room temperature for 2 hours. The obtained product is shown in structural formula (2-21). The yield is 70%. The nuclear magnetic resonance spectra are as follows. 1 H NMR、 13 C NMR、 19 F NMR spectrum is shown in Figure 21. The product: 1 H NMR (600 MHz, CDCl3) δ 7.96 (td, J = 7.7, 2.0 Hz, 1H), 7.61 - 7.37 (m, 5H), 7.31 (t, J = 7.3 Hz, 1H), 7.16 - 7.02 (m, 2H), 4.59 (dd, J = 9.6, 4.8 Hz, 0.5H), 4.55 - 4.47 (m, 1H), 4.43 (t, J = 9.7 Hz, 0.5H), 4.29 (dd, J = 11.1, 6.9 Hz, 1H), 4.17 (dd, J = 11.1, 2.5 Hz, 1H), 3.88 (m, 1H). 13 C NMR (151 MHz, CDCl3) δ 174.2, 169.3, 162.4 (d, J = 259.7 Hz), 139.9, 133.5 (d, J = 9.1 Hz), 132.5, 128.9, 126.9, 124.5, 124.5 (d, J = 9.1 Hz), 123.5 (d, J = 3.8 Hz), 116.8 (d, J = 22.6 Hz), 82.1 (d, J = 179.1 Hz), 53.5 (d, J = 3.0 Hz), 40.2 (d, J = 20.9 Hz). 19 F NMR (565 MHz, CDCl3) δ -110.80, -212.11. HRMS (ESI-TOF) m / z: [M+Na] + calculated for C 17 H 14 F2N2NaOS 355.0687,found 355.0683.

[0137] Example 23

[0138]

[0139] The experimental method of this example is basically the same as that of Example 1. The raw material used in this example is (N-[(allyl(phenyl)ethyl)aminothiocarbamoyl]-3- methoxybenzamide. The reaction is carried out at room temperature for 2 hours. The obtained product is shown in structural formula (2-23). The yield is 70%. The nuclear magnetic resonance 1 H NMR, 13 C NMR, 19 The F NMR spectrum is shown in Figure 23. The product: 1 H NMR (500 MHz, CDC13) δ 7.76 - 7.64 (m, 2H), 7.59 - 7.43 (m, 4H), 7.36 - 7.22 (m, 2H), 7.06 - 6.99 (m, 1H), 4.59 (dd, J = 9.6, 4.8 Hz, 0.5H), 4.56 - 4.47 (m, 1H), 4.42 (t, J = 9.7 Hz, 0.5H), 4.28 (dd, J = 11.2, 7.0 Hz, 1H), 4.17 (dd, J = 11.1, 2.4 Hz, 1H), 3.88 (m, 1H), 3.79 (s, 3H). 13 C NMR (151 MHz, CDC13) δ 175.9, 169.1, 159.4, 140.1, 137.4, 129.1, 128.9, 126.9, 124.6, 122.4, 119.3, 113.6, 82.2 (d, J = 178.9 Hz), 55.2, 53.3 (d, J = 3.0 Hz), 40.2 (d, J = 20.7 Hz). 19 F NMR (565 MHz, CDC13) δ -211.85. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 18 H 17 F N2NaO2S 327.0574, found 367.0896.

[0140] Example 24

[0141]

[0142] The experimental method of this example is basically the same as that of Example 1. The raw material used in this example is (N-[(allyl(phenyl)ethyl)aminothiocarbamoyl]-2-furan carboxamide. The reaction is carried out at room temperature for 2 hours. The obtained product is shown in structural formula (2-24). The yield is 73%. The nuclear magnetic resonance 1 H NMR, 13 C NMR,19 The F NMR spectrum is shown in Figure 24, and the product: 1 H NMR (600 MHz, CDC13) δ 7.62 - 7.42 (m, 5H), 7.31 (td, J = 7.3, 1.3 Hz, 1H), 7.04 (d, J = 3.4 Hz, 1H), 6.43 (dd, J = 3.4, 1.7 Hz, 1H), 4.58 (dd, J = 9.6, 4.7 Hz, 0.5H), 4.54 - 4.47 (m, 1H), 4.42 (t, J = 9.7 Hz, 0.5H), 4.28 (dd, J = 11.1, 6.9 Hz, 1H), 4.16 (dd, J = 11.1, 2.4 Hz, 1H), 3.87 (m, 1H). 13 C NMR (151 MHz, CDC13) δ 168.6, 167.2, 151.1, 146.2, 139.9, 128.9, 126.8, 124.5, 117.6, 111.7, 82.1 (d, J = 179.2 Hz), 53.4 (d, J = 2.9 Hz), 40.3 (d, J = 21.1 Hz). 19 F NMR (565 MHz, CDC13) δ -211.9. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 15 H 13 FN2NaO2S 327.0574, found 327.0563.

[0143] Example 25

[0144]

[0145] The experimental method of this example is basically the same as that of Example 1. The raw material used in this example is (N-[(allyl (phenyl) ethyl) aminothiocarbamoyl]-1- thiophene carboxamide. The reaction is carried out at room temperature for 2 hours. The product obtained is shown in structural formula (2-25). The yield is 76%. The nuclear magnetic resonance 1 H NMR、 13 C NMR、 19 The F NMR spectrum is shown in Figure 25, and the product: 1H NMR (500 MHz, CDC13) δ 7.77 (dd, J = 3.7, 1.3 Hz, 1H), 7.59 - 7.40 (m, 5H), 7.36 - 7.27 (m, 1H), 7.04 (dd, J = 5.0, 3.7 Hz, 1H), 4.58 (dd, J = 9.6, 4.8 Hz, 0.5H), 4.54 - 4.45 (m, 1H), 4.41 (t, J = 9.7 Hz, 0.5H), 4.28 (dd, J = 11.1, 7.0 Hz, 1H), 4.16 (dd, J = 11.1, 2.4 Hz, 1H), 3.87 (m, 1H). 13 CNMR (126 MHz, CDC13) δ 170.9, 168.3, 142.3, 139.8, 132.3, 132.2, 128.9, 127.9, 126.8, 124.5, 82.1 (d, J = 179.0 Hz), 53.3 (d, J = 3.0 Hz), 40.3 (d, J = 21.0 Hz). 19 F NMR (565 MHz, CDC13) δ -211.85. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 15 H 13 FN2NaOS2343.0346, found343.0334.

[0146] Example 26

[0147]

[0148] The experimental method of this example is basically the same as that of Example 1. The raw material used in this example is (N-[(allyl(phenyl)ethyl)aminothiocarbamoyl]-tert- butylcarboxamide, and the reaction is carried out at room temperature for 2 hours. The product obtained is shown in the structural formula (2-26). The yield is 66%. The nuclear magnetic resonance 1 H NMR、 13 C NMR、 19 The F NMR spectrum is shown in Figure 26, and the product: 1 H NMR (600 MHz, CDC13) δ 7.63 - 7.37 (m, 4H), 7.36 - 7.23 (m, 1H), 4.56 (dd, J = 9.6, 4.8 Hz, 0.5H), 4.54 - 4.45 (m, 1H), 4.39 (d, J = 9.7 Hz, 0.5H), 4.22 (dd, J = 11.0, 6.9 Hz, 1H), 4.12 (dd, J = 11.0, 2.5 Hz, 1H), 3.83 (m, 1H), 1.16 (s, 9H). 13C NMR (151 MHz, CDC13) δ 190.9, 167.9, 140.2, 128.6, 126.2, 124.1, 82.2 (d, J = 179.0 Hz), 52.9 (d, J = 2.9 Hz), 41.2, 39.9 (d, J = 21.0 Hz), 27.2. 19 F NMR (565 MHz, CDC13) δ -211.5. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 15 H 19 FN2NaOS 317.1094, found 317.1085.

[0149] Example 27

[0150]

[0151] The experimental method of this example is basically the same as that of Example 1. The raw material used in this example is (N-[(allylthio)carbamoyl]-cyclohexylcarboxamide, and the reaction is carried out at room temperature for 2 hours. The product obtained is shown in the structural formula (2-27). The yield is 49%. The nuclear magnetic resonance 1 H NMR、 13 C NMR、 19 The F NMR spectrum is shown in Figure 27, and the product: 1 H NMR (600 MHz, CDC13) δ 7.50 - 7.39 (m, 4H), 7.30 - 7.27 (m, 1H), 4.55 (dd, J = 9.5, 4.7 Hz, 0.5H), 4.49 - 4.43 (m, 1H), 4.38 (t, J = 9.8 Hz, 0.5H), 4.19 (dd, J = 11.1, 6.9 Hz, 1H), 4.10 (dd, J = 11.1, 2.4 Hz, 1H), 3.80 (m, 1H), 2.33 (tt, J = 11.3, 3.6 Hz, 1H), 1.95 - 1.85 (m, 2H), 1.71 (dq, J = 11.9, 3.5 Hz, 2H), 1.66 - 1.52 (m, 2H), 1.38 (m, 2H), 1.24 - 1.12 (m, 2H). 13 C NMR (151 MHz, CDC13) δ 188.3, 167.8, 140.1, 128.9, 126.5, 124.3, 82.2 (d, J = 178.7 Hz), 53.2 (d, J = 2.8 Hz), 47.8, 40.0 (d, J = 20.9 Hz). 29.1, 29.1, 26.0, 25.8, 25.7. 19F NMR (565 MHz, CDCI3) δ -211.53. HRMS (ESI-TOF) m / z: [M + Na] 343.1251, found 334.1232. + calculated for C 17 H 21 FN2NaOS 343.1251, found334.1232.

[0152] Example 28

[0153]

[0154] The experimental method of this example is basically the same as that of Example 1. The raw material used in this example is (N-[(2- chlorophenyl)ethyl]aminothiocarbamoyl]-benzylcarbamide. The reaction was carried out at room temperature for 2 hours. The product obtained is shown in structural formula (2-27). The yield is 60%. The nuclear magnetic resonance spectra are as follows: 1 H NMR、 13 C NMR、 19 The F NMR spectrum is shown in Figure 27. The product: 1 H NMR (500 MHz, CDCI3) δ 7.45 - 7.35 (m, 2H), 7.35 - 7.18 (m, 8H), 4.52 (dd, J = 9.6, 4.7 Hz, 0.5H), 4.48 - 4.39 (m, 1H), 4.34 (t, J = 9.7 Hz, 0.5H), 4.17 (dd, J = 11.2, 7.0 Hz, 1H), 4.07 (dd, J = 11.2, 2.5 Hz, 1H), 3.78 (m, 1H), 3.71 (s, 2H). 13 C NMR (151 MHz, CDCI3) δ 183.1, 168.4, 139.7, 135.9, 129.8, 128.9, 128.2, 126.7, 126.4, 124.4, 82.1 (d, J = 178.8 Hz), 53.3 (d, J = 3.0 Hz), 47.2, 40.0 (d, J = 20.2 Hz). 19 F NMR (565 MHz, CDCI3) δ -211.91. HRMS (ESI-TOF) m / z: [M + Na] 343.1251, found 334.1232. + calculated for C 18 H 17 FN2NaOS 351.0938, found351.0930.

[0155] Example 29

[0156]

[0157] The experimental method of this example is basically the same as that of Example 1. The raw material used in this example is (N-[2-methylallyl(phenyl)ethyl)aminothiocarbamoyl]-benzamide. The reaction was carried out at room temperature for 2 hours. The obtained product is shown in structural formula (2-29). The yield is 76%. The nuclear magnetic resonance 1 H NMR, 13 C NMR, 19 The F NMR spectrum is shown in Figure 29. The product: 1 H NMR (600 MHz, CDC13) δ 8.15-8.08 (m, 2H), 7.56-7.42 (m, 5H), 7.41-7.28 (m, 3H), 4.54 (dd, J = 48.2, 9.4 Hz, 1H), 4.35 (dd, J = 47.4, 9.4 Hz, 1H), 4.15 (d, J = 10.9 Hz, 1H), 3.91 (d, J = 10.9 Hz, 1H), 1.67 (s, 3H). 13 C NMR (151 MHz, CDC13) δ 176.2, 169.4, 140.2, 136.0, 132.2, 129.8, 128.9, 128.0, 126.8, 124.6, 85.4 (d, J = 183.6 Hz), 59.1 (d, J = 2.4 Hz), 48.8 (d, J = 19.0 Hz), 20.9 (d, J = 2.3 Hz). 19 F NMR (565 MHz, CDC13) δ -212.42. HRMS (ESI-TOF) m / z: [M+Na] + calculated for C 18 H 17 FN2NaOS 351.0938, found 351.0931.

[0158] Example 30

[0159]

[0160] The experimental method of this example is basically the same as that of Example 1. The raw material used in this example is (N-[2-methylallyl(phenyl)ethyl)aminothiocarbamoyl]-benzamide. The reaction was carried out at room temperature for 2 hours. The obtained product is shown in structural formula (2-29). The yield is 76%. The nuclear magnetic resonance 1 H NMR, 13 C NMR, 19 The F NMR spectrum is shown in Figure 30. The product: 1HNMR (500 MHz, CDC13) δ 8.20 - 8.07 (m, 2H), 7.59 - 7.45 (m, 5H), 7.37 (m, 3H), 4.31 - 4.18 (m, 2H), 3.81 (m, 1H), 1.54 (d, J = 9.4 Hz, 3H), 1.50 (d, J = 9.1 Hz, 3H). 13 C NMR (151 MHz, CDC13) δ 176.1, 169.7, 140.0, 136.1, 132.1, 129.8, 129.0, 128.0, 126.8, 124.6, 96.2 (d, J = 172.5 Hz), 52.6 (d, J = 4.2 Hz), 49.3 (d, J = 25.6 Hz), 25.6 (d, J = 23.6 Hz), 21.8 (d, J = 24.5 Hz). 19 F NMR (565 MHz, CDC13) δ -139.7. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 19 H 19 FN2NaOS 365.1094, found 365.1091.

[0161] Example 31

[0162]

[0163] The experimental method of this example is basically the same as that of Example 1. The raw material used in this example is (N-[cyclohex-2-en-1-yl(phenyl)ethyl)aminothiocarbamoyl]-benzamide. The reaction is carried out at room temperature for 2 hours. The obtained product is shown in structural formula (2-31). The yield is 80%. The nuclear magnetic resonance 1 H NMR、 13 C NMR、 19 F NMR spectrum is shown in Figure 31. The product: 1 HNMR (500 MHz, CDC13) δ 8.20 - 8.07 (m, 2H), 7.59 - 7.45 (m, 5H), 7.37 (m, 3H), 4.31 - 4.18 (m, 2H), 3.81 (m, 1H), 1.54 (d, J = 9.4 Hz, 3H), 1.50 (d, J = 9.1 Hz, 3H). 13CNMR (151 MHz, CDC13) δ 176.2, 170.7, 139.1, 136.2, 132.0, 129.7, 129.1, 127.9, 127.6, 126.9, 91.0 (d, J = 174.2 Hz), 62.0 (d, J = 3.5 Hz), 47.0 (d, J = 25.0 Hz), 28.1 (d, J = 19.8 Hz), 25.2, 16.8 (d, J = 6.3 Hz). 19 F NMR (565 MHz, CDC13) δ -175.19. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 20 H 19 FN2NaOS 377.1094, found 377.1085.

[0164] Example 32

[0165]

[0166] The experimental method of this example is basically the same as that of Example 1. The raw material used in this example is (N-[cinnamyl(phenyl)ethyl)aminothiocarbamoyl]-benzamide. The reaction is carried out at room temperature for 2 hours. The product obtained is shown in the structural formula (2-32). The yield is 70%. The nuclear magnetic resonance 1 H NMR、 13 C NMR、 19 F NMR spectrum is shown in Figure 32. The product: 1 H NMR (600 MHz, CDC13) δ 8.10 (d, J = 7.8 Hz, 2H), 7.70 - 7.27 (m, 13H), 5.49 (dd, J = 47.5, 9.0 Hz, 1H), 4.32 (qd, J = 11.2, 5.8 Hz, 2H), 4.15 - 3.96 (m, 1H). 13 C NMR (151 MHz, CDC13) δ 176.0, 169.4, 140.0, 136.1, 136.0, 132.2, 129.8, 129.6, 128.9, 128.8, 128.0, 126.8, 126.8, 124.7, 94.0 (d, J = 179.5 Hz), 53.6 (d, J = 4.0 Hz), 46.4 (d, J = 26.7 Hz). 19 F NMR (565 MHz, CDC13) δ -167.30, -167.33. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 23 H19 FN2NaOS413.1094, found413.1105.

[0167] Example 33

[0168]

[0169] The experimental method of this example is basically the same as that of Example 1. The raw material used in this example is (N-[6-dec-5-yl(phenyl)ethyl)aminothiocarbamoyl]-benzamide. The reaction is carried out at room temperature for 2 hours. The product obtained is shown in the structural formula (2-33). The yield is 76%. The nuclear magnetic resonance 1 H NMR、 13 C NMR、 19 The F NMR spectrum is shown in Figure 33. The product: 1 HNMR (600 MHz, CDCl3) δ 8.07 - 7.92 (m, 6H), 7.49 - 7.20 (m, 26H), 4.90 - 4.73 (m, 1H), 4.58 - 4.34 (m, 6H), 4.02 (dt, J = 10.2, 7.0 Hz, 1H), 3.28 (t, J = 8.9 Hz, 2H), 1.91 - 1.32 (m, 21H), 1.31 - 1.04 (m, 14H), 0.89 (m, 10H), 0.73 (m, 10H). 13 C NMR (151 MHz, CDCl3) δ 176.3, 176.2, 169.0, 168.0, 139.7, 138.9, 136.1, 132.0, 131.9, 129.7, 129.7, 129.0, 128.8, 127.9, 127.4, 127.3, 127.0, 126.9, 93.7 (d, J = 177.8 Hz), 91.1 (d, J = 173.8 Hz), 64.9, 64.8 (d, J = 4.7 Hz), 49.9 (d, J = 24.0 Hz), 49.3 (d, J = 21.7 Hz), 36.5, 36.4, 34.7 (d, J = 20.6 Hz), 30.5, 27.7 (d, J = 12.3 Hz), 27.2, 22.7, 22.3, 18.3 (d, J = 2.5 Hz), 17.8 (d, J = 2.9 Hz), 13.8, 13.7, 13.7. 19 FNMR (471 MHz, CDCl3) δ -177.38, -178.64. HRMS (ESI-TOF) m / z: [M+Na] + calculated forC 24 H 29FN2NaOS 435.1877, found 435.1881.

[0170] Example 34

[0171]

[0172] The experimental method of this example is basically the same as that of Example 1. The raw material used in this example is (N-[3-buten-1-yl(phenyl)ethyl)aminothiocarbamoyl]-benzamide, and the reaction is carried out at room temperature for 2 hours. The obtained product is shown as structural formula (2-34). The yield is 45%. The nuclear magnetic resonance 1 H NMR, 13 C NMR, 19 The F NMR spectrum is shown in Figure 34, and the product is: 1 H NMR (500 MHz, CDC13) δ 7.80 (d, J = 7.7 Hz, 2H), 7.46 (t, J = 7.6 Hz, 2H), 7.39 - 7.20 (m, 6H), 4.72 - 4.44 (m, 2H), 4.01 - 3.82 (m, 2H), 3.70 (m, 1H), 2.52 (dt, J = 15.4, 5.4 Hz, 1H), 2.30 (m, 1H). 13 CNMR (126 MHz, CDC13) δ 174.4, 164.1, 145.9, 136.8, 131.5, 129.5, 129.3, 127.8, 127.4, 126.3, 83.8 (d, J = 178.0 Hz), 49.8, 40.3 (d, J = 20.8 Hz), 26.2 (d, J = 3.2 Hz). 19 F NMR (565 MHz, CDC13) δ -216.29. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 18 H 17 FN2NaOS 351.0938, found 351.0931.

[0173] Example 35

[0174]

[0175] The experimental method of this example is basically the same as that of Example 1. The raw material used in this example is (N-[3-buten-1-yl(phenyl)ethyl)aminothiocarbamoyl]-benzamide, and the reaction is carried out at room temperature for 2 hours. The obtained product is shown as structural formula (2-34). The yield is 45%. The nuclear magnetic resonance 1 H NMR, 13 C NMR,19 The F NMR spectrum is shown in Figure 35, and the product is: 1 H NMR (600 MHz, CDC13) δ 8.27 - 8.19 (m, 2H), 7.54 - 7.46 (m, 1H), 7.42 (dd, J = 8.3, 6.8 Hz, 2H), 7.33 (t, J = 7.5 Hz, 2H), 7.29 - 7.19 (m, 3H), 4.50 (dd, J = 9.6, 5.1 Hz, 0.5H), 4.45 - 4.36 (m, 1H), 4.32 (t, J = 9.1 Hz, 0.5H), 4.03 (m, 2H), 3.54 - 3.43 (m, 1H), 3.33 (m, 2H), 3.10 (t, J = 7.3 Hz, 2H), 2.22 (m, 1H), 1.96 (m, 1H). 13 C NMR (151 MHz, CDC13) δ 174.4, 163.5, 138.6, 137.4, 131.5, 129.5, 128.9, 128.7, 127.9, 126.7, 83.5 (d, J = 178.3 Hz), 56.3, 47.7, 39.6 (d, J = 20.6 Hz), 33.6, 25.3 (d, J = 3.0 Hz). 19 F NMR (565 MHz, CDC13) δ -215.93. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 20 H 21 FN2NaOS 379.1251, found 379.1255.

[0176] Example 36

[0177]

[0178] The experimental method of this example is basically the same as that of Example 1. The raw material used in this example is (N-[3-buten-1-yl(ethylpropionate-1-yl)ethyl)aminothiocarbamoyl]-benzamide. The reaction is carried out at room temperature for 2 hours. The product obtained is shown in structural formula (2-36). The yield is 69%. The nuclear magnetic resonance 1 H NMR、 13 C NMR、 19 The F NMR spectrum is shown in Figure 36, and the product is: 1H NMR (600 MHz, CDCI3) δ 8.12 - 8.05 (m, 2H), 7.45 - 7.27 (m, 3H), 4.45 (dd, J = 9.6, 5.2 Hz, 0.5H), 4.43 - 4.34 (m, 1H), 4.32 (dd, J = 9.6, 8.1 Hz, 0.5H), 4.07 (q, J = 7.1 Hz, 2H), 4.04 - 3.93 (m, 2H), 3.65 (m, 1H), 3.57 (m, 1H), 3.51 - 3.41 (m, 1H), 2.78 (td, J = 6.5, 2.8 Hz, 2H), 2.30 (m, 1H), 2.04 (m, 1H), 1.19 (t, J = 7.1 Hz, 3H). 13 C NMR (151 MHz, CDCI3) δ 174.2, 171.9, 163.8, 137.1, 131.5, 129.4, 127.9, 83.6 (d, J = 177.9 Hz), 60.8, 50.3, 48.0, 39.8 (d, J = 20.9 Hz), 32.5, 25.6 (d, J = 3.6 Hz), 14.1. 19 F NMR (565 MHz, CDCI3) δ -216.3. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 17 H 21 FN2NaO3S 375.1149, found 375.1160.

[0179] Example 37

[0180]

[0181] The experimental method of this example is basically the same as that of Example 1. The raw material used in this example is (N-[4-methyl-3-penten-1-yl (phenethyl) ethyl) aminothiocarbamoyl]-benzamide. The reaction is carried out at room temperature for 2 hours. The obtained product is shown in structural formula (2-37). The yield is 91%. The H NMR, C NMR and F NMR spectra are shown in Figures 37, 38 and 39 respectively. The product is: 1 H NMR、 13 C NMR、 19 F NMR、 1HNMR (600 MHz, CDC13) δ 8.27 - 8.20 (m, 2H), 7.51 - 7.45 (m, 1H), 7.42 (dd, J = 8.2, 6.7 Hz, 2H), 7.32 (td, J = 7.2, 1.6 Hz, 2H), 7.29 - 7.21 (m, 3H), 4.09 (m, 1H), 3.95 (m, 1H), 3.43 - 3.30 (m, 3H), 3.09 (m, 2H), 2.24 (dq, J = 13.7, 3.8 Hz, 1H), 1.85 (m, 1H), 1.44 (dd, J = 21.9, 13.6 Hz, 6H). 13 C NMR (151 MHz, CDC13) δ 174.1, 164.4, 138.6, 137.5, 131.4, 129.5, 128.9, 128.7, 127.9, 126.7, 96.0 (d, J = 172.4 Hz), 56.0, 49.7 (d, J = 25.7 Hz), 49.7, 33.5, 25.4 (d, J = 24.1 Hz), 25.0 (d, J = 4.3 Hz), 22.6 (d, J = 24.2 Hz). 19 F NMR (565 MHz, CDC13) δ -137.77. HRMS (ESI-TOF) m / z: [M + Na] C + calculated for C 22 H 25 FN2NaOS 407.1564, found 407.1574.

[0182] Example 38

[0183]

[0184] To the reaction tube was added PhI(OPiv)2(85.3 mg, 0.21 mmol), 3 mL of 1,4-dioxane and Et3N-3HF (117 mg, 0.7 mmol), after stirring for 5 minutes, N-[but-2-yn-1-yl(phenyl)aminothioformyl]benzamide (61.7 mg, 0.2 mmol) was added, and the reaction was allowed to proceed at room temperature for 3 hours, TLC monitoring of the starting material N-[but-2-yn-1-yl(phenyl)aminothioformyl]benzamide until it was completely consumed, the reaction system was quenched with saturated sodium bicarbonate solution, extracted with dichloromethane three times, the combined organic layer was washed with saturated brine, and then concentrated under reduced pressure, the residue was separated by column chromatography with a certain proportion of eluent to obtain 53.6 mg of pure product, the structure of which is shown in formula (4-1). The yield was 83%. (1, when the molar ratio of N-[but-2-yn-1-yl(phenyl)aminothioformyl]benzamide to PhI(OPiv)2 was 3, and the other conditions were the same as above, the yield was 70%; 2, when the molar ratio of N-[but-2-yn-1-yl(phenyl)aminothioformyl]benzamide to PhI(OPiv)2 was 2, and the other conditions were the same as above, the yield was 72%; 3, when the molar ratio of N-[but-2-yn-1-yl(phenyl)aminothioformyl]benzamide to PhI(OPiv)2 was 1, and the other conditions were the same as above, the yield was 79%; 4, when the molar ratio of N-[but-2-yn-1-yl(phenyl)aminothioformyl]benzamide to fluorine source was 1:20, and the other conditions were the same as above, the yield was 82%; 5, when the molar ratio of N-[but-2-yn-1-yl(phenyl)aminothioformyl]benzamide to fluorine source was 1:1, and the other conditions were the same as above, the yield was 78%; 6, when the oxidant was PhI(OAc)2, and the other conditions were the same as above, the yield was 66%; 7, when the oxidant was PhI(OAd)2, and the other conditions were the same as above, the yield was 83%; when the fluorine source was py-8HF, and the other conditions were the same as above, the yield was 50%; 8, when the organic solvent was acetonitrile, and the other conditions were the same as above, the yield was 17%; 9, when the organic solvent was dichloromethane, and the other conditions were the same as above, the yield was 30%; 9, when the organic solvent was 1,4-dioxane, and the other conditions were the same as above, the yield was 77%; 9, when the organic solvent was diethyl ether, and the other conditions were the same as above, the yield was 56%; 10, when the solvent was ethyl acetate, and the other conditions were the same as above, the yield was 67%; 11, when the solvent was tetrahydrofuran, and the other conditions were the same as above, the yield was 53%; 12, when the solvent was methyl tert-butyl ether, and the other conditions were the same as above, the yield was 36%; 13, when the reaction time was 1 hour, and the other conditions were the same as above, the yield was 52%; 14, when the reaction time was 4 hours, and the other conditions were the same as above, the yield was 82%; 15, when the reaction time was 8 hours, and the other conditions were the same as above, the yield was 82%) product: 1H NMR (500 MHz, CDC13) δ 8.12 - 7.99 (m, 2H), 7.49 (d, J = 7.6 Hz, 2H), 7.41 (dt, J = 13.5, 7.5 Hz, 3H), 7.28 (q, J = 7.9 Hz, 3H), 4.74 (m, 2H), 1.99 (dt, J = 17.0, 2.3 Hz, 3H). 13 C NMR (126 MHz, CDC13) δ 176.0, 167.9, 148.1 (d, J = 252.8 Hz), 139.8, 135.9, 132.3, 129.8, 129.1, 128.1, 127.1, 124.8, 108.1 (d, J = 25.9 Hz), 52.0 (d, J = 6.4 Hz), 16.3 (d, J = 27.5 Hz). 19 F NMR (471 MHz, CDC13) δ -92.0. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 18 H 15 FN2NaOS 349.0781, found 349.0779.

[0185] Example 39

[0186]

[0187] The experimental method of this example is substantially the same as that of Example 38. The raw material used in this example is N-[but-2-yn-1-yl(4-methoxyphenyl)aminothioformyl]benzamide. The reaction is carried out at room temperature for 3 hours. The product obtained is shown in the structural formula (4-2). The yield is 74%. The product: 1 H NMR (500 MHz, CDC13) δ 8.12 - 7.99 (m, 2H), 7.49 (d, J = 7.6 Hz, 2H), 7.41 (dt, J = 13.5, 7.5 Hz, 3H), 7.28 (q, J = 7.9 Hz, 3H), 4.74 (m, 2H), 1.99 (dt, J = 17.0, 2.3 Hz, 3H). 13 C NMR (126 MHz, CDC13) δ 176.0, 167.9, 148.1 (d, J = 252.8 Hz), 139.8, 135.9, 132.3, 129.8, 129.1, 128.1, 127.1, 124.8, 108.1 (d, J = 25.9 Hz), 52.0 (d, J = 6.4 Hz), 16.3 (d, J = 27.5 Hz). 19F NMR (471 MHz, CDCb) δ -92.15. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 19 H 17 FN2NaO2S 379.0887, found 379.0885.

[0188] Example 40

[0189]

[0190] The experimental method of this example is basically the same as that of Example 38. The raw material used in this example is N-[but-2-yn-l-yl(4-formylphenyl)aminothio- carbonyl]benzamide. The reaction was carried out at room temperature for 3 hours. The product obtained is shown in the structural formula (4-3). The yield is 79%. The product: 1 H NMR (500 MHz, CDCb) δ 8.20 - 8.03 (m, 4H), 7.78 (d, J = 8.6 Hz, 2H), 7.51 (t, J = 7.4 Hz, 1H), 7.41 (t, J = 7.6 Hz, 2H), 4.86 (t, J = 2.7 Hz, 2H), 2.66 (s, 3H), 2.08 (dt, J = 17.0, 2.3 Hz, 3H). 13 C NMR (151 MHz, CDCb) δ 196.9, 176.1, 167.9, 148.5 (d, J = 253.8 Hz), 143.7, 135.6, 134.8, 132.6, 129.8, 129.2, 128.3, 123.8, 107.5 (d, J = 26.1 Hz), 51.3 (d, J = 6.6 Hz), 26.6, 16.3 (d, J = 27.5 Hz). 19 F NMR (471 MHz, CDCb) δ -92.15. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 20 H 17 FN2NaO2S 391.0887, found391.0894.

[0191] Example 41

[0192]

[0193] The experimental method of this example is basically the same as that of Example 38. The raw material used in this example is N-[but-2-yn-1-yl(4-iodophenyl)aminothiocarbamoyl]tert-butylcarboxamide, and the reaction is carried out at room temperature for 3 hours. The obtained product is shown in the structural formula (4-4). The yield is 52%. The product: 1 H NMR (500 MHz, CDCl3) δ 7.73 (d, J = 8.9 Hz, 2H), 7.43 - 7.30 (m, 2H), 4.78 - 4.61 (m, 2H), 2.02 (dt, J = 17.0, 2.2 Hz, 3H), 1.15 (s, 9H). 13 C NMR (126 MHz, CDCl3) δ 190.81, 166.68, 148.07 (d, J = 253.0 Hz), 139.57, 137.74, 125.71, 107.71 (d, J = 25.6 Hz), 90.65, 50.97 (d, J = 6.7 Hz), 41.22, 27.18, 16.23 (d, J = 27.5 Hz). 19 F NMR (471 MHz, CDCl3) δ -92.15. HRMS (ESI-TOF) m / z: [M+Na] + calculated for C 16 H 18 FIN2NaOS455.0061, found 455.0070.

[0194] Example 42

[0195]

[0196] The experimental method of this example is basically the same as that of Example 38. The raw material used in this example is N-[but-2-yn-1-yl(4-iodophenyl)aminothiocarbamoyl]tert-butylcarboxamide, and the reaction is carried out at room temperature for 3 hours. The obtained product is shown in the structural formula (4-4). The yield is 52%. The product: 1 H NMR (500 MHz, CDCl3) δ 7.73 (d, J = 8.9 Hz, 2H), 7.43 - 7.30 (m, 2H), 4.78 - 4.61 (m, 2H), 2.02 (dt, J = 17.0, 2.2 Hz, 3H), 1.15 (s, 9H). 13C NMR (126 MHz, CDC13) δ 176.2, 167.1, 162.6 (d, J = 246.0 Hz), 159.8, 148.1 (d, J = 253.5 Hz), 141.2 (d, J = 10.7 Hz), 133.2, 132.5, 129.9 (d, J = 9.2 Hz), 125.3, 120.0, 118.9 (d, J = 3.0 Hz), 113.4 (d, J = 21.1 Hz), 112.1 (d, J = 25.6 Hz), 111.9, 107.9 (d, J = 25.4 Hz), 55.8, 51.5 (d, J = 6.6 Hz), 16.3 (d, J = 27.5 Hz). 19 F NMR (471 MHz, CDC13) δ -91.96, -111.04. HRMS (ESI-TOF) m / z: [M + Na] + Caled. for C 19 H 16 F2N2NaO2S 397.0793, found 397.0798.

[0197] Example 43

[0198]

[0199] The experimental method of this example is basically the same as that of Example 38, and the starting material used in this example is N-[but-2-yn-1-yl(2-fluorophenyl)aminothio carbamoyl] cyclohexylformamide. The reaction is carried out at room temperature for 3 hours, and the product obtained is shown in the structural formula (4-6). The yield is 69%. The product: 1 H NMR (500 MHz, CDC13) δ 7.36 (m, 2H), 7.25 - 7.15 (m, 2H), 4.61 (dt, J = 4.6, 2.3 Hz, 2H), 2.26 (tt, J = 11.1, 3.6 Hz, 1H), 2.02 (dt, J = 16.9, 2.3 Hz, 3H), 1.82 (m, 2H), 1.67 (dt, J = 12.6, 3.4 Hz, 2H), 1.62 - 1.54 (m, 1H), 1.41 - 1.08 (m, 5H). 13C NMR (126 MHz, CDCI3) δ 188.2, 167.7, 157.4 (d, J = 252.3 Hz), 147.8 (d, J = 252.7 Hz), 129.7 (d, J = 7.9 Hz), 128.8 (d, J = 1.8 Hz), 127.2 (d, J = 12.1 Hz), 124.5 (d, J = 3.7 Hz), 116.8 (d, J = 19.8 Hz), 108.7 (d, J = 25.9 Hz), 51.0 (d, J = 6.6 Hz), 47.5, 29.0, 26.0, 25.7, 16.3 (d, J = 27.6 Hz). 19 F NMR (471 MHz, CDCI3) δ -92.30, -118.77. HRMS (ESI-TOF) m / z: [M + Na] + C 18 H 20 F2N2NaOS 373.1157, found 373.1159.

[0200] Example 44

[0201]

[0202] The experimental method of this example is basically the same as that of Example 38, and the raw material used in this example is N-[but-2-yn-1-yl(1-naphthyl)aminothiocarbamoyl]-2- bromobenzamide. The reaction is carried out at room temperature for 3 hours, and the product obtained is shown in structural formula (4-7). The yield is 62%. The product: 1 H NMR (600 MHz, CDCI3) δ 8.09 - 7.83 (m, 2H), 7.71 (dt, J = 6.3, 3.6 Hz, 1H), 7.64 - 7.38 (m, 6H), 7.03 (m, 2H), 4.84 (m, 1H), 4.80 - 4.66 (m, 1H), 2.11 (dt, J = 16.9, 2.3 Hz, 3H). 13 C NMR (126 MHz, CDCI3) δ 176.1, 169.7, 148.3 (d, J = 253.3 Hz), 136.7, 136.3, 134.6, 134.1, 132.1, 131.5, 129.3, 129.1, 128.7, 127.2, 126.6, 126.6, 125.6, 125.1, 122.4, 122.0, 108.7 (d, J = 26.6 Hz), 53.0 (d, J = 6.0 Hz), 16.4 (d, J = 27.5 Hz). 19F NMR (471 MHz, CDCb) δ -92.23. HRMS (ESI-TOF) m / z: [M + Na] + C 22 H 16 BrFN2NaO2S 477.0043, found 477.0074.

[0203] Example 45

[0204]

[0205] The experimental method of this example is substantially the same as that of Example 38. The raw material used in this example is N-[but-2-yn-l-yl(benzyl)aminothio carbonyl]benzamide. The reaction is carried out at room temperature for 3 hours. The product obtained is shown in structural formula (4-8). The yield is 72%. The product: 1 H NMR (500 MHz, CDCb) δ 8.37 - 8.25 (m, 2H), 7.57 - 7.47 (m, 1H), 7.43 (dd, J = 8.2, 6.7 Hz, 2H), 7.40 - 7.28 (m, 5H), 5.02 (s, 2H), 4.26 (dd, J = 3.6, 2.3 Hz, 2H), 1.99 (dt, J = 17.0, 2.3 Hz, 3H). 13 C NMR (126 MHz, CDCb) δ 175.8, 168.8, 148.0 (d, J = 252.3 Hz), 136.2, 135.1, 132.1, 129.7, 129.0, 128.3, 128.2, 128.1, 108.5 (d, J = 26.1 Hz), 51.2, 49.2 (d, J = 6.4 Hz), 16.4 (d, J = 27.6 Hz). 19 F NMR (471 MHz, CDCb) δ -92.23. HRMS (ESI-TOF) m / z: [M + Na] + C 19 H 17 FN2NaOS 363.0938, found 363.0931.

[0206] Example 46

[0207]

[0208] The experimental method of this example is basically the same as that of Example 38. The raw material used in this example is N-[but-2-yn-1-yl(tert-butyl-piperidin-1- carboxylate-4-yl)aminothiocarbamoyl]-4-methoxybenzamide. The reaction is carried out at room temperature for 3 hours. The obtained product is shown in structural formula (4-9). The yield is 86%. The product: 1 H NMR (500 MHz, CDC13) δ 8.20 (d, J = 8.5 Hz, 2H), 6.93 (d, J = 8.6 Hz, 2H), 4.80 (tt, J = 12.2, 4.0 Hz, 1H), 4.33 (t, J = 2.9 Hz, 4H), 3.86 (s, 3H), 2.88 (s, 2H), 2.00 (dt, J = 17.0, 2.4 Hz, 3H), 1.95 - 1.87 (m, 2H), 1.73 (qd, J = 12.2, 4.5 Hz, 2H), 1.49 (s, 9H). 13 C NMR (126 MHz, CDC13) δ 175.1, 167.5, 162.9, 154.5, 147.9 (d, J = 252.0 Hz), 131.5, 128.9, 113.3, 108.6 (d, J = 25.4 Hz), 79.9, 55.2 (d, J = 29.7 Hz), 45.8, 45.8, 43.2, 28.8, 28.4, 16.4 (d, J = 27.6 Hz). 19 F NMR (471 MHz, CDC13) δ -92.56. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 22 H 30 FN3NaO4S 486.1833, found 486.1826.

[0209] Example 47

[0210]

[0211] The experimental method of this example is basically the same as that of Example 38. The raw material used in this example is N-[but-2-yn-1-yl(tert-butyl-piperidin-1- carboxylate-4-yl)aminothiocarbamoyl]-4-methoxybenzamide. The reaction is carried out at room temperature for 3 hours. The obtained product is shown in structural formula (4-9). The yield is 86%. The product: 1H NMR (500 MHz, CDC13) δ 7.76 (dd, J = 3.8, 1.3 Hz, 1H), 7.67 - 7.53 (m, 2H), 7.53 - 7.42 (m, 3H), 7.32 (t, J = 7.4 Hz, 1H), 7.04 (dd, J = 5.0, 3.7 Hz, 1H), 4.80 (dt, J = 3.4, 1.7 Hz, 2H), 2.45 - 2.24 (m, 2H), 1.16 (t, J = 7.5 Hz, 3H). 13 C NMR (126 MHz, CDC13) δ 170.7, 167.1, 152.5 (d, J = 256.3 Hz), 142.3, 139.5, 132.2, 132.2, 128.9, 127.9, 127.0, 124.6, 106.9 (d, J = 26.9 Hz), 51.9 (d, J = 6.5 Hz), 24.1 (d, J = 26.0 Hz), 10.1. 19 F NMR (471 MHz, CDC13) δ -101.3. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 17 H 15 N2NaOS2369.0502, found 369.0506.

[0212] Example 48

[0213]

[0214] The experimental method of this example is basically the same as that of Example 38. The raw material used in this example is N-[2-2-dimethyl-dodec-3-yn-5-yl(phenyl)aminothiocarbamoyl]benzamide. The reaction is carried out at room temperature for 3 hours. The product obtained is shown in structural formula (4-11). The yield is 79%. The product: 1 H NMR (500 MHz, CDC13) δ 7.76 (dd, J = 3.8, 1.3 Hz, 1H), 7.67 - 7.53 (m, 2H), 7.53 - 7.42 (m, 3H), 7.32 (t, J = 7.4 Hz, 1H), 7.04 (dd, J = 5.0, 3.7 Hz, 1H), 4.80 (dt, J = 3.4, 1.7 Hz, 2H), 2.45 - 2.24 (m, 2H), 1.16 (t, J = 7.5 Hz, 3H). 13C NMR (126 MHz, CDCI3) d 176.0, 168.0, 157.7 (d, J = 256.5 Hz), 138.6, 136.2, 131.9, 129.7, 129.0, 127.9, 127.5, 126.9, 110.8 (d, J = 29.1 Hz), 64.5 (d, J = 7.3 Hz), 36.3 (d, J = 24.5 Hz), 32.2 (d, J = 2.4 Hz), 31.6, 29.3, 28.9, 27.7 (d, J = 3.7 Hz), 22.8, 22.5, 14.0. 19 F NMR (471 MHz, CDCI3) d -98.5. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 28 H 35 FN2NaOS 489.2346, found 489.2353.

[0215] Example 49

[0216]

[0217] The experimental method of this example is basically the same as that of Example 38. The raw material used in this example is N-[8-benzyloxyoct-5-yl (phenyl) aminothio carbonyl] benzamide. The reaction is carried out at room temperature for 3 hours. The product obtained is shown in structural formula (4-12). The yield is 67%. The product: 1 H NMR (500 MHz, CDCI3) d 8.11 - 8.02 (m, 2H), 7.53 - 7.30 (m, 12H), 7.27 (m, 1H), 5.26 (dt, J = 6.1, 3.1 Hz, 1H), 4.56 (d, J = 2.2 Hz, 2H), 3.70 (t, J = 6.5 Hz, 2H), 2.82 - 2.58 (m, 2H), 1.82 - 1.70 (m, 1H), 1.69 - 1.61 (m, 1H), 1.40 (m, 2H), 0.82 (t, J = 7.4 Hz, 3H). 13 C NMR (126 MHz, CDCI3) d 176.1, 167.6, 149.1 (d, J = 256.6 Hz), 138.6, 138.0, 136.1, 132.0, 129.7, 129.1, 128.4, 128.0, 127.6, 127.6, 127.6, 126.9, 114.3 (d, J = 24.0 Hz), 72.9, 65.7, 63.1 (d, J = 2.3 Hz), 31.7 (d, J = 25.6 Hz), 31.8, 31.6, 16.6, 13.9.19 F NMR (471 MHz, CDC13) δ -100.46. HRMS (ESI-TOF) m / z: [M + Na] 511.1826, found 511.1830. + Calculated for C 29 H 29 F N2NaO2S 511.1826, found 511.1830.

[0218] Example 50

[0219]

[0220] PhI(OPiv)2 (162.5 mg, 0.4 mmol) was added to the reaction tube, followed by 3 mL of toluene and Et3N·3HF (96.7 mg, 0.6 mmol). After stirring for 5 minutes, (3-methyl-2-buten-1-yl)(phenyl)aminothiocarbamoyl fluoride (44.7 mg, 0.2 mmol) was added. The reaction was carried out at room temperature for 4 hours. The starting material (3-methyl-2-buten-1-yl)(phenyl)aminothiocarbamoyl fluoride) was monitored by TLC until it was completely consumed. The reaction system was quenched with saturated sodium bicarbonate solution and extracted three times with dichloromethane. The combined organic layers were washed with saturated brine and then concentrated under reduced pressure. The residue was separated by column chromatography using a certain proportion of eluent to obtain 43.2 mg of pure product, the structure of which is shown in formula (6-1). The yield was 90%. (1. When the molar ratio of (3-methyl-2-buten-1-yl)(phenyl)aminothiocarbamoyl fluoride to PhI(OPiv)2 is 3, and other conditions are the same as above, the yield is 90%; 2. When the molar ratio of (3-methyl-2-buten-1-yl)(phenyl)aminothiocarbamoyl fluoride to PhI(OPiv)2 is 1, and other conditions are the same as above, the yield is 56%; 3. When the molar ratio of (3-methyl-2-buten-1-yl)(phenyl)aminothiocarbamoyl fluoride to PhI(OPiv)2 is 3, and other conditions are the same as above, the yield is 56%; The yield was 90% when the molar ratio of acyl fluoride to fluorine source was 1:20, and other conditions were the same as above; 5. The yield was 21% when the molar ratio of (3-methyl-2-buten-1-yl)(phenyl)aminothiocarbamoyl fluoride to fluorine source was 1:1, and other conditions were the same as above; 6. The yield was 79% when the oxidant was PhI(OAc)2, and other conditions were the same as above; 7. The yield was 91% when the oxidant was PhI(OAd)2, and other conditions were the same as above; The yield was 5% when the source was py·8HF and other conditions were the same as above; 8. The yield was 73% when the organic solvent was acetonitrile and other conditions were the same as above; 9. The yield was 51% when the organic solvent was dichloromethane and other conditions were the same as above; 9. The yield was 76% when the organic solvent was 1,4-dioxane and other conditions were the same as above; 9. The yield was 78% when the organic solvent was diethyl ether and other conditions were the same as above; 10. The yield was 78% when the solvent was xylene and other conditions were the same as above. Under the same conditions, the yield was 82%; 11. When the solvent was chlorobenzene, the yield was 76%; 12. When the solvent was trifluorotoluene, the yield was 84%; 13. When the reaction time was 1 hour, the yield was 62%; 14. When the reaction time was 4 hours, the yield was 90%; 15. When the reaction time was 8 hours, the yield was 90%. Products: 1 HNMR (500MHz, CDCl3) δ7.43–7.35(m,4H),7.20(m,1H),4.22(m,1H),4.09(m,1H),3.85(m,1H),1.49(m,6H). 13C NMR (126 MHz, CDCI3) δ 169.5, 138.5, 129.1, 125.7, 122.0, 96.12 (d, J = 172.7 Hz), 51.17 (d, J = 5.0 Hz), 48.05 (d, J = 27.2 Hz), 25.15 (d, J = 23.7 Hz), 22.13 (d, J = 24.4 Hz). 19 F NMR (565 MHz, CDCI3) δ -141.4. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 12 H 14 FNNaOS262.0672, found262.0679.

[0221] Example 51

[0222]

[0223] The experimental method of this example is basically the same as that of Example 50. The raw material used in this example is (3-methyl-2-buten-1 -yl)(4-methoxyphenyl)aminothiocarbonyl fluoride. The reaction is carried out at room temperature for 4 hours. The product obtained is shown in the structural formula (6-2). The yield is 81%. The product: 1 H NMR (500 MHz, CDCI3) δ 7.25 - 7.17 (m, 2H), 6.87 - 6.80 (m, 2H), 4.09 (dd, J = 10.8, 8.0 Hz, 1 H), 3.95 (dd, J = 10.8, 3.9 Hz, 1 H), 3.81 - 3.67 (m, 4H), 1.42 (t, J = 21.9 Hz, 6H). 13 C NMR (126 MHz, CDCI3) δ 169.5, 138.5, 129.1, 125.7, 122.0, 96.12 (d, J = 172.7 Hz), 51.17 (d, J = 5.0 Hz), 48.05 (d, J = 27.2 Hz), 25.15 (d, J = 23.7 Hz), 22.13 (d, J = 24.4 Hz). 19 F NMR (565 MHz, CDCI3) δ -141.4. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 13 H 16 FNNaO2S292.0778, found292.0770.

[0224] Example 52

[0225]

[0226] The experimental method of this example is basically the same as that of Example 50. The raw material used in this example is (3-methyl-2-buten-1-yl)(4-nitrophenyl) aminothioformic fluoride. The reaction is carried out at room temperature for 4 hours. The product obtained is shown in the structural formula (6-3). The yield is 91%. The product: 1 H NMR (500 MHz, CDC13) δ 8.33 - 8.20 (m, 2H), 7.72 - 7.60 (m, 2H), 4.29 (dd, J = 10.6, 7.9 Hz, 1H), 4.20 (dd, J = 10.6, 4.3 Hz, 1H), 3.94 (m, 1H), 1.53 (d, J = 2.7 Hz, 3H), 1.49 (d, J = 2.6 Hz, 3H). 13 C NMR (126 MHz, CDC13) δ 170.1, 143.9, 143.9, 124.7, 120.4, 95.7 (d, J = 173.7 Hz), 50.5 (d, J = 5.0 Hz), 47.9 (d, J = 27.1 Hz), 25.2 (d, J = 23.9 Hz), 22.4 (d, J = 24.2 Hz). 19 F NMR (565 MHz, CDC13) δ -142.36. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 12 H 13 FN2NaO3S 307.1523, found 307.1532.

[0227] Example 53

[0228]

[0229] The experimental method of this example is basically the same as that of Example 50. The raw material used in this example is (3-methyl-2-buten-1-yl)(4-nitrophenyl) aminothioformic fluoride. The reaction is carried out at room temperature for 4 hours. The product obtained is shown in the structural formula (6-3). The yield is 91%. The product: 1H NMR (500 MHz, CDC13) δ 7.59 (dd, J = 8.1, 1.4 Hz, 1H), 7.31 (td, J = 7.6, 1.4 Hz, 1H), 7.24 (dd, J = 7.9, 1.7 Hz, 1H), 7.17 (td, J = 7.7, 1.7 Hz, 1H), 4.05 (d, J = 10.7 Hz, 1H), 3.97 (m, 1H), 3.92 - 3.79 (m, 1H), 1.53 (d, J = 21.2 Hz, 3H), 1.43 (d, J = 21.4 Hz, 3H). 13 C NMR (126 MHz, CDC13) δ 170.2, 137.5, 133.9, 130.1, 129.6, 128.7, 122.5, 95.8 (d, J = 172.7 Hz), 51.1 (d, J = 5.3 Hz), 49.5 (d, J = 26.3 Hz), 25.25 (d, J = 23.7 Hz), 23.05 (d, J = 24.0 Hz). 19 F NMR (565 MHz, CDC13) δ -142.0. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 12 H 13 BrFNNaOS 339.9777, found 339.9778.

[0230] Example 54

[0231]

[0232] The experimental method of this example is substantially the same as that of Example 50. The starting material used in this example is (3-methyl-2-buten-1-yl)(3- iodophenyl)aminothiocarbonyl fluoride. The reaction is carried out at room temperature for 4 hours. The product obtained is shown in structural formula (6-5). The yield is 93%. The product: 1 H NMR (600 MHz, CDC13) δ 7.67 (m, 1H), 7.46 (m, 1H), 7.37 - 7.32 (m, 1H), 7.03 (t, J = 8.0 Hz, 1H), 4.11 (dd, J = 10.7, 7.9 Hz, 1H), 3.99 (dd, J = 10.7, 3.9 Hz, 1H), 3.78 (m, 1H), 1.41 (m, 6H). 13C NMR (151 MHz, CDCI3) δ 169.6, 139.6, 134.6, 130.5, 130.3, 121.0, 96.0 (d, J = 173.0 Hz), 94.1, 50.9 (d, J = 5.0 Hz), 48.0 (d, J = 27.2 Hz), 25.2 (d, J = 23.8 Hz), 22.2 (d, J = 24.2 Hz). 19 F NMR (565 MHz, CDCI3) δ -141.6. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 12 H 13 FINNaOS 387.9639, found 387.9650.

[0233] Example 55

[0234]

[0235] The experimental method of this example is basically the same as that of Example 50. The raw material used in this example is (3-methyl-2-buten-1-yl)(1-naphthyl)aminothiocarbonyl fluoride. The reaction is carried out at room temperature for 4 hours. The product obtained is shown in the structural formula (6-6). The yield is 96%. The product: 1 HNMR (500 MHz, CDCI3) δ 7.77 (m, 3H), 7.54 - 7.36 (m, 3H), 7.32 (d, J = 7.3 Hz, 1H), 4.11 (t, J = 9.4 Hz, 1H), 3.95 (d, J = 34.1 Hz, 2H), 1.53 (d, J = 21.2 Hz, 3H), 1.42 (d, J = 21.2 Hz, 3H). 13 C NMR (126 MHz, CDCI3) δ 170.30, 135.00, 134.59, 129.64, 128.95, 128.61, 127.09, 126.52, 125.53, 125.10, 124.15, 122.71, 122.28, 95.60 (d, J = 173.2 Hz), 52.80, 49.54, 25.01 (d, J = 24.0 Hz), 23.29. 19 F NMR (565 MHz, CDCI3) δ -142.51, -144.47. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 16 H 16 FNNaOS 312.0829, found 312.0826.

[0236] Example 56

[0237]

[0238] The experimental method of this example is basically the same as that of Example 50. The raw material used in this example is (3-methyl-2-buten-1-yl)(phenyl)methyl)aminothiocarbonyl fluoride. The reaction is carried out at room temperature for 4 hours. The obtained product is shown in the structural formula (6-7). The yield is 89%. The product: 1 HNMR (600 MHz, CDC13) δ 7.31 - 7.26 (m, 2H), 7.26 - 7.21 (m, 1H), 7.21 - 7.16 (m, 2H), 4.39 (s, 2H), 3.67 (m, 1H), 3.47 (dd, J = 11.0, 8.4 Hz, 1H), 3.40 (dd, J = 10.9, 4.3 Hz, 1H), 1.27 (t, J = 21.3 Hz, 6H). 13 C NMR (151 MHz, CDC13) δ 170.40, 135.45, 128.81, 128.34, 128.00, 96.10 (d, J = 171.9 Hz), 48.60, 48.36 (d, J = 5.0 Hz), 48.18 (d, J = 27.0 Hz), 25.12 (d, J = 24.0 Hz), 22.00 (d, J = 24.4 Hz). 19 F NMR (565 MHz, CDC13) δ -141.43. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 13 H 16 F NMR (565 MHz, CDC13) δ -141.43. HRMS (ESI-TOF) m / z: [M + Na]

[0239] Example 57

[0240]

[0241] The experimental method of this example is basically the same as that of Example 50. The raw material used in this example is (3-methyl-2-buten-1-yl)(phenyl)methyl)aminothiocarbonyl fluoride. The reaction is carried out at room temperature for 4 hours. The obtained product is shown in the structural formula (6-7). The yield is 89%. The product: 1 HNMR (500 MHz, CDC13) δ 3.98 (tt, J = 11.9, 3.8 Hz, 1H), 3.74 (m, 1H), 3.66 (m, 2H), 1.90 - 1.73 (m, 4H), 1.73 - 1.65 (m, 1H), 1.52 - 1.32 (m, 11H). 13C NMR (126MHz, CDCl3) δ169.6,96.7(d,J=171.7Hz),53.6,48.2(d,J=26.4hz),45.0( d,J=5.0Hz),30.3(d,J=27.2Hz),25.6,25.5,25.5(d,J=23.9Hz),25.4,21.8,21.6. 19 FNMR(565MHz,CDCl3)δ-140.86.HRMS(ESI-TOF)m / z:[M+Na] + Calculated for C 18 H 20 FNNaOS268.1142,found268.1151.

[0242] Example 58

[0243]

[0244] The experimental method used in this embodiment is basically the same as that in Example 50. The raw material used in this embodiment is (3-methyl-2-buten-1-yl)(tert-butylpiperidine-1-carboxylate) aminothiocarboxylic acid fluoride. The reaction is carried out at room temperature for 4 hours, and the resulting product is shown in structural formulas (6-9). The yield is 87%. Product: 1 H NMR (500MHz, CDCl3) δ4.34–3.98(m,3H),3.68(m,1H),3.60–3.50(m,2H),2.70(s,2H),1.70–1.61(m,2H),1.55(m,2H),1.44–1.29(m,15H). 13 CNMR(151MHz, CDCl3)δ169.98,154.44,96.26(d,J=172.3Hz),79.83,51.77,48.28(d,J=27.2H z), 44.90 (d, J = 5.0Hz), 43.0, 29.19 (d, J = 29.3Hz), 28.35, 25.33 (d, J = 23.9Hz), 21.98, 21.82. 19 F NMR(565MHz, CDCl3)δ-141.25,141.66.HRMS(ESI-TOF)m / z:[M+Na] + Calculated for C 16 H 27 FN2NaO3S 369.1619,found369.1618.

[0245] Example 59

[0246]

[0247] The experimental method of this example is substantially the same as that of Example 50. The raw material used in this example is 3-ethyl 5-methyl 4-(2-chlorophenyl)-2-((2-(fluorocarbonyl)(3-methyl-2-en-1-yl)amino)ethoxy)methyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate. The reaction is carried out at room temperature for 4 hours. The obtained product is shown in the structural formula (6-10). The yield is 67%. The product: 1 HNMR (600 MHz, CDC13) δ 7.40 (m, 1H), 7.28-7.22 (m, 2H), 7.15 (m, 1H), 7.10-7.03 (m, 1H), 5.42 (s, 1H), 4.86-4.63 (m, 2H), 4.11-4.01 (m, 2H), 3.87-3.70 (m, 5H), 3.70-3.50 (m, 5H), 2.39 (s, 3H), 1.54-1.41 (m, 6H), 1.21 (t, J = 7.1 Hz, 3H). 13 C NMR (126 MHz, CDC13) δ 171.3, 171.2, 168.0, 167.2, 145.9, 144.9, 144.9, 144.6, 144.6, 132.3, 131.5, 131.5, 129.2, 127.3, 126.9, 126.8, 103.8, 103.8, 101.4, 101.3, 96.9, 95.5, 68.1, 68.1, 67.8, 67.6, 59.8, 50.8, 49.4, 49.4, 49.3, 49.2, 48.5, 48.5, 48.3, 48.3, 44.4, 44.4, 37.0, 37.0, 29.7, 25.5, 25.5, 25.3, 25.3, 22.0, 22.0, 21.8, 21.8, 19.1, 19.1, 14.3. 19 F NMR (471 MHz, CDC13) δ -142.13, -142.19. HRMS (ESI-TOF) m / z: [M+Na] + calculated for C 26 H 32 ClFN2NaO6S577.1546, found 577.1535.

[0248] Example 60

[0249]

[0250] The experimental method of this example is basically the same as that of Example 50. The raw material used in this example is (phenyl)aminothiocarbonyl fluoride. The reaction was carried out at room temperature for 4 hours. The obtained product is shown in structural formula (6-1). The yield was 75%. The product: 1 HNMR (600 MHz, CDC13) δ 7.47 - 7.34 (m, 9H), 7.21 (tt, J = 5.5, 3.0 Hz, 1H), 5.50 (dd, J = 47.2, 9.1 Hz, 1H), 4.30 (m, 2H), 4.07 (m, 1H). 13 C NMR (126 MHz, CDC13) δ 169.0, 138.6, 136.1, 135.9, 129.7, 129.6, 129.1, 128.7, 126.8, 126.7, 125.8, 122.0, 93.96 (d, J = 180.3 Hz), 52.12 (d, J = 3.8 Hz), 45.16 (d, J = 28.7 Hz). 19 FNMR (565 MHz, CDC13) δ -168.37. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 16 H 14 FNNaOS310.0672, found 310.0675.

[0251] Example 61

[0252]

[0253] The experimental method of this example is basically the same as that of Example 50. The raw material used in this example is (cyclohex-2-en-1-yl)(phenyl)aminothiocarbonyl fluoride. The reaction was carried out at room temperature for 4 hours. The obtained product is shown in structural formula (6-12). The yield was 53%. The product: 1 H NMR (500 MHz, CDC13) δ 7.34 (m, 2H), 7.26 - 7.20 (m, 1H), 7.20 - 7.14 (m, 2H), 4.77 (m, 1H), 4.37 (m, 1H), 3.80 (dt, J = 13.8, 6.1 Hz, 1H), 2.04 (m, 1H), 1.87 - 1.76 (m, 1H), 1.72 - 1.57 (m, 2H), 1.57 - 1.33 (m, 2H). 13CNMR (126 MHz, CDC13) δ 13C NMR (126 MHz, Chloroform-d) δ 171.27, 137.55, 129.37, 127.30, 125.98, 92.14 (d, J = 175.3 Hz), 61.48 (d, J = 4.7 Hz), 47.14 (d, J = 25.4 Hz), 28.72 (d, J = 19.3 Hz), 25.98, 17.08 (d, J = 7.6 Hz). 19 FNMR (565 MHz, CDC13) δ -176.14. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 13 H 14 FNNaOS 274.0668, found 274.0668.

[0254] Example 62

[0255]

[0256] The experimental method of this example is substantially the same as that of Example 50. The starting material used in this example is (E)-dec-6-en-5-yl(phenyl)aminothioformic fluoride. The reaction is carried out at room temperature for 4 hours. The product obtained is shown in the structural formula (6-13). The yield of the trans product is 58% and the yield of the cis product is 22%. The product: 1 H NMR (500 MHz, CDC13) δ 7.38 - 7.27 (m, 4H), 7.18 (tt, J = 6.9, 1.4 Hz, 1H), 4.54 (m, 1H), 4.33 (dd, J = 9.2, 3.4 Hz, 1H), 3.30 (dd, J = 9.4, 8.0 Hz, 1H), 1.85 - 1.68 (m, 2H), 1.67 - 1.50 (m, 3H), 1.43 (m, 1H), 1.32 - 1.19 (m, 4H), 0.92 (t, J = 7.3 Hz, 3H), 0.78 (td, J = 8.5, 7.0, 4.8 Hz, 3H). 13 C NMR (126 MHz, CDC13) δ 168.2, 137.6, 129.3, 126.7, 125.2, 93.9 (d, J = 177.4 Hz), 63.6 (d, J = 4.7 Hz), 48.3 (d, J = 23.4 Hz), 34.7, 34.5, 31.1, 27.1, 22.3, 18.2 (d, J = 2.7 Hz), 13.8 (d, J = 8.3 Hz). 19F NMR (471 MHz, CDC13) δ -179.22. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 17 H 24 FNNaOS 332.1446, found 332.1445. 1 HNMR (500 MHz, CDC13) δ 7.46 - 7.39 (m, 2 H), 7.39 - 7.33 (m, 2 H), 7.31 - 7.24 (m, 1 H), 4.95 - 4.75 (m, 1 H), 4.47 (q, J = 6.1 Hz, 1 H), 4.28 (dt, J = 9.8, 6.7 Hz, 1 H), 1.89 - 1.60 (m, 5 H), 1.53 (m, 1 H), 1.40 - 1.15 (m, 4 H), 1.01 (t, J = 7.2 Hz, 3 H), 0.82 (t, J = 7.2 Hz, 3 H). 13 C NMR (126 MHz, CDC13) δ 169.4, 138.3, 129.3, 126.8, 125.5, 91.0 (d, J = 173.6 Hz), 64.0 (d, J = 1.9 Hz), 49.5 (d, J = 25.8 Hz), 36.5 (d, J = 21.1 Hz), 28.4 (d, J = 1.8 Hz), 27.7 (d, J = 2.2 Hz), 22.8, 17.9 (d, J = 3.1 Hz), 13.8 (d, J = 6.3 Hz). 19 F NMR (471 MHz, CDC13) δ -179.54. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 17 H 24 FNNaOS 332.1455, found 332.1445.

[0257] Example 63

[0258]

[0259] The experimental method of this example is substantially the same as that of Example 50. The starting material used in this example is but-2-en-1-yl(phenyl)aminothiocarbonyl fluoride. The reaction is carried out at room temperature for 4 hours. The product obtained is shown in structural formula (6-14). The yield of the trans product is 60% and the yield of the cis product is 24%. The product: 1H NMR (500 MHz, CDC13) δ 7.41 - 7.27 (m, 4 H), 7.14 (qt, J = 5.5, 2.9 Hz, 1 H), 4.70 (ddq, J = 48.5, 9.1, 6.1 Hz, 1 H), 4.18 (ddd, J = 10.7, 7.0, 1.1 Hz, 1 H), 4.08 (dd, J = 10.6, 3.4 Hz, 1 H), 3.62 (dtd, J = 9.1, 7.2, 3.4 Hz, 1 H), 1.41 (dd, J = 24.0, 6.1 Hz, 3 H). 13 C NMR (126 MHz, CDC13) δ 169.0, 138.6, 129.1, 125.8, 122.0, 90.5 (d, J = 175.1 Hz), 52.2 (d, J = 5.3 Hz), 45.0 (d, J = 24.4 Hz), 18.8 (d, J = 22.4 Hz). 19 F NMR (471 MHz, CDC13) δ -170.47. HRMS (ESI-TOF) m / z: [M + Na] + Calculated for C 11 H 12 FNNaOS248.0516, found 248.0519. 1 H NMR (500 MHz, CDC13) δ 7.37 - 7.28 (m, 4 H), 7.14 (dq, J = 8.6, 4.0 Hz, 1 H), 4.78 (dqd, J = 46.9, 6.3, 4.9 Hz, 1 H), 4.15 (dd, J = 10.5, 7.8 Hz, 1 H), 3.94 (dd, J = 10.4, 4.7 Hz, 1 H), 3.87 (ddt, J = 14.8, 7.8, 4.9 Hz, 1 H), 1.41 (dd, J = 23.6, 6.2 Hz, 3 H). 13 C NMR (126 MHz, CDC13) δ 169.39, 138.53, 129.13, 125.82, 122.09, δ 90.50 (d, J = 174.8 Hz), 51.39 (d, J = 4.4 Hz), 44.56 (d, J = 23.3 Hz), 17.05 (d, J = 22.8 Hz). 19 F NMR (471 MHz, CDC13) δ -175.30. HRMS (ESI-TOF) m / z: [M + Na] + Calculated for C 11 H 12 FNNaOS248.0516, found 248.0519.

[0260] Example 64

[0261]

[0262] The experimental method used in this embodiment is basically the same as that in Example 50. The starting material used in this embodiment is (E)-benzyl(4-((4-methoxyphenyl)thio)-2-en-1-yl)aminothioformyl fluoride. The reaction is carried out at room temperature for 4 hours, and the resulting product is shown in structural formula (6-15). The yield is 43%. Product: 1 H NMR (500MHz, CDCl3) δ7.35–7.15(m,7H),6.80–6.70(m,2H),4.65–4.40(m,3H),4.34(d,J=14.8Hz,1H),3.74(s,3H),3.70–3.59(m,3H),3.03(m,1H). 13 C NMR (126MHz, CDCl3) δ170.4,160.3,136.4,135.8,128.9,128.3,128.0,121.9,115 .0,82.9(d,J=175.3Hz),55.4,54.1(d,J=18.3Hz),51.7,48.6,42.1(d,J=2.9Hz). 19 F NMR(471MHz, CDCl3)δ–221.57.HRMS(ESI-TOF)m / z:[M+Na] + Calculated for C 19 H 20 FNNaO2S2400.0812,found400.0811.

[0263] Example 65

[0264]

[0265] The experimental method used in this embodiment is basically the same as that in Example 50. The raw material used in this embodiment is allyl (phenyl)aminothiocarbamoyl fluoride. The reaction is carried out at room temperature for 4 hours, and the resulting product is shown in structural formula (6-16). The yield is 50%. Product: 1 HNMR (500MHz, CDCl3) δ7.42(m,4H),7.24(m,1H),4.62(d,J=7.2Hz,1H),4.52(d,J=7 .3Hz, 1H), 4.31 (dd, J=10.7, 6.7Hz, 1H), 4.10 (dd, J=10.6, 2.6Hz, 1H), 3.96 (m, 1H). 13CNMR (151 MHz, CDC13) δ 168.97, 138.58, 129.11, 125.86, 122.04, 82.49 (d, J = 179.2 Hz), 51.76 (d, J = 3.4 Hz), 39.06 (d, J = 22.3 Hz). 19 F NMR (565 MHz, CDC13) δ -211.10. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 10 H 10 FNNaOS234.0359, found 234.0362.

[0266] Example 66

[0267]

[0268] The experimental method of this example is substantially the same as that of Example 50. The starting material used in this example is (2-methylallyl)(phenyl)aminothiocarbonyl fluoride. The reaction is carried out at room temperature for 4 hours. The product obtained is shown in structural formula (6-17). The yield is 39%. The product: 1 HNMR (600 MHz, CDC13) δ 7.39 (m, 4H), 7.25 - 7.18 (m, 1H), 4.59 (dd, J = 48.1, 9.3 Hz, 1H), 4.36 (dd, J = 47.1, 9.1 Hz, 1H), 4.07 (d, J = 10.4 Hz, 1H), 3.90 (d, J = 10.4 Hz, 1H), 1.66 (d, J = 1.4 Hz, 3H). 13 C NMR (151 MHz, CDC13) δ 169.28, 138.70, 129.12, 125.85, 122.12, 85.60 (d, J = 184.2 Hz), 57.80 (d, J = 2.9 Hz), 48.56 (d, J = 19.8 Hz), 21.94 (d, J = 2.8 Hz). 19 F NMR (565 MHz, CDC13) δ -210.89. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 11 H 12 FNNaOS248.0516, found 248.0519.

[0269] Example 67

[0270]

[0271] The experimental method of this example is basically the same as that of Example 50. The raw material used in this example is (4-methyl-pent-3-en-1-yl)(phenyl)aminothiocarbonyl fluoride. The reaction is carried out at room temperature for 4 hours. The obtained product is shown in structural formula (6-18). The yield is 70%. The product: 1 H NMR (500 MHz, CDC13) δ 7.31 (t, J = 7.7 Hz, 2H), 7.25 - 7.09 (m, 3H), 3.86 - 3.63 (m, 3H), 2.33 (m, 1H), 2.03 (m, 1H), 1.42 (dd, J = 21.6, 13.4 Hz, 6H). 13 C NMR (151 MHz, CDC13) δ 165.2, 143.0, 129.2, 127.0, 125.8, 95.8 (d, J = 172.0 Hz), 52.8 (d, J = 25.0 Hz), 51.1, 26.2 (d, J = 4.4 Hz), 24.6 (d, J = 24.3 Hz), 23.2 (d, J = 24.3 Hz). 19 F NMR (565 MHz, CDC13) δ -138.79. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 13 H 16 F NMR (565 MHz, CDC13) δ -138.79. HRMS (ESI-TOF) m / z: [M + Na]

[0272] Example 68

[0273]

[0274] The experimental method of this example is basically the same as that of Example 50. The raw material used in this example is (4-methyl-pent-3-en-1-yl)(phenyl)aminothiocarbonyl fluoride. The reaction is carried out at room temperature for 4 hours. The obtained product is shown in structural formula (6-18). The yield is 70%. The product: 1 H NMR (500 MHz, CDC13) δ 7.31 (t, J = 7.7 Hz, 2H), 7.25 - 7.09 (m, 3H), 3.86 - 3.63 (m, 3H), 2.33 (m, 1H), 2.03 (m, 1H), 1.42 (dd, J = 21.6, 13.4 Hz, 6H). 13C NMR (126 MHz, CDCI3) δ 165.2, 136.3, 128.7, 128.1, 127.7, 95.7 (d, J = 172.1 Hz), 52.5 (d, J = 25.3 Hz), 51.9, 46.9, 25.7 (d, J = 4.4 Hz), 24.7 (d, J = 24.1 Hz), 23.1 (d, J = 24.3 Hz). 19 F NMR (471 MHz, CDCI3) δ -138.7. HRMS (ESI-TOF) m / z: [M + Na] + C 14 H 18 FNNaOS 290.0985, found 290.0978.

[0275] Example 69

[0276]

[0277] The experimental method of this example is substantially the same as that of Example 50. The starting material used in this example is (4-methyl-pent-3-en-1 -yl)(ethyl propan-2-ylate-1 -yl)aminothiocarbonyl fluoride. The reaction is carried out at room temperature for 4 hours. The product obtained is shown in structural formula (6-20). The yield is 51 %. The product: 1 H NMR (500 MHz, CDCI3) δ 4.16 (q, J = 7.1 Hz, 2H), 3.80 - 3.45 (m, 5H), 2.65 (q, J = 6.4 Hz, 2H), 2.30 (m, 1 H), 1.91 (m, 1 H), 1.44 (dd, J = 21.7, 12.2 Hz, 6H), 1.28 (t, J = 7.1 Hz, 3H). 13 C NMR (126 MHz, CDCI3) δ 171.88, 165.07, 95.72 (d, J = 172.0 Hz), 60.74, 52.50 (d, J = 25.2 Hz), 48.96, 45.99, 32.90, 25.96 (d, J = 4.3 Hz), 24.58 (d, J = 24.1 Hz), 23.12 (d, J = 24.3 Hz), 14.14. 19 F NMR (471 MHz, CDCI3) δ -138.68. HRMS (ESI-TOF) m / z: [M + Na] + C 12 H 20 FNNaO3S 300.1040, found 300.1033.

[0278] Example 70

[0279]

[0280] The method of this example is: adding (Z)-N-(5-(fluoromethyl)-3-phenylthiazolidine-2- ylidene)benzamide (2-1) synthesized by the application (31.4 mg, 0.1 mmol) into a reaction tube, adding 0.5 mL of DMF, then adding potassium tert-butoxide (56.2 mg, 5 mmol), and reacting at 100°C for 12 hours. TLC is used to monitor the complete consumption of the raw material (Z)-N-(5-(fluoromethyl)-3-phenylthiazolidine-2-ylidene)benzamide (2-1). The reaction system is quenched with water, extracted with dichloromethane three times, and the organic layers are combined and washed with saturated brine. The organic layer is concentrated under reduced pressure, and the residue is separated by column chromatography using a certain proportion of eluent to obtain 22.1 mg of pure product, which has a structural formula as shown in 7-1, and the yield is 75%. The product: 1 H NMR (500 MHz, CDCl3) δ 8.21-8.13 (m, 2H), 7.65-7.58 (m, 2H), 7.55 (dd, J = 8.7, 7.0 Hz, 2H), 7.48-7.40 (m, 2H), 7.40-7.32 (m, 2H), 6.89 (d, J = 1.5 Hz, 1H), 2.36 (d, J = 1.4 Hz, 3H). 13 C NMR (151 MHz, CDCl3) δ 174.19, 167.41, 138.59, 136.82, 131.44, 129.34, 129.13, 128.26, 127.98, 125.93, 122.58, 121.88, 12.80. HRMS (ESI-TOF) m / z: [M+Na] + calculated for C 17 H 14 N2NaOS 317.0725, found 317.0721.

[0281] Example 71

[0282]

[0283] The method of this example is: to the reaction tube is added the 5-(2-fluoropropane)-3-phenylthiazolidine-2-one (6-1) synthesized by the application (71.8 mg, 0.3 mmol), 4 ml of ethanol is added, and potassium hydroxide (101.0 mg, 1.8 mmol) is added, heated to reflux for 12 hours, TLC monitoring of the raw material 5-(2-fluoropropane)-3-phenylthiazolidine-2-one (6-1) to complete consumption, the reaction system is concentrated under reduced pressure, and the residue is separated by column chromatography with a certain proportion of eluent to obtain 18.6 mg of pure product, which has a structural formula as shown in 8-1, and the yield is 70%. The product 1 H NMR (500 MHz, CDC13) δ 7.38 (t, J = 7.8 Hz, 2H), 7.30-7.25 (m, 1H), 7.22 (d, J = 7.7 Hz, 2H), 4.18 (m, 3H), 3.78 (dd, J = 14.6, 7.8 Hz, 1H), 3.00 (dd, J = 7.8, 5.2 Hz, 1H), 1.49 (s, 3H), 1.19 (s, 6H). 13 C NMR (151 MHz, CDC13) δ 155.52, 141.47, 130.89-123.85 (m), 61.89, 51.68, 46.90 (d, J = 107.5 Hz), 30.20, 22.89, 14.59. HRMS (ESI-TOF) m / z: [M + Na] + calculated for C 14 H 19 NNaO2S288.1034, found 288.1031.

[0284] Example 72

[0285]

[0286] The method of this example is: to the reaction tube is added the 5-(2-fluoropropane)-3-phenylthiazolidine-2-one (6-1) synthesized by the application (71.8 mg, 0.3 mmol), 4 ml of ethanol is added, and potassium hydroxide (101.0 mg, 1.8 mmol) is added, heated to reflux for 12 hours, TLC monitoring of the raw material 5-(2-fluoropropane)-3-phenylthiazolidine-2-one (6-1) to complete consumption, the reaction system is concentrated under reduced pressure, and the residue is separated by column chromatography with a certain proportion of eluent to obtain 18.6 mg of pure product, which has a structural formula as shown in 8-1, and the yield is 70%. The product 1H NMR (500 MHz, CDC13) δ 8.21 - 8.12 (m, 2H), 7.67 - 7.60 (m, 2H), 7.57 (dd, J = 8.7, 7.0 Hz, 2H), 7.52 - 7.41 (m, 2H), 7.37 (dd, J = 8.2, 6.8 Hz, 2H), 7.08 (s, 1H), 4.58 (q, J = 6.4 Hz, 1H), 3.55 (m, 2H), 1.58 (d, J = 6.4 Hz, 5H), 1.25 (q, J = 6.6 Hz, 4H). 13 C NMR (151 MHz, CDC13) δ 174.41, 167.59, 138.51, 136.69, 131.55, 129.63, 129.39, 129.19, 128.41, 128.00, 125.95, 122.50, 71.55, 64.36, 22.64, 15.32. HRMS (ESI-TOF) m / z: [M + Na] + C 20 H 20 N2NaO2S 375.1143, found 375.1140.

[0287] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used in the description of the application herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the application.

[0288] As used herein, the term "comprising" is open-ended, meaning that it includes the recited elements, but not excluding other elements.

[0289] As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed items.

[0290] While the embodiments of the application have been illustrated and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made therein without departing from the spirit and scope of the application, which is defined by the following claims and their equivalents.

Claims

1. A class of (Z)-N-(5-(fluoromethyl / 1-fluoroalkyl / fluoro(aryl)methyl)-3-alkyl / substituted alkyl / arylthiazolyl-2-ylidene)-alkyl / arylformamides and (Z)-N-(6-(fluoromethyl / 1-fluoroalkyl-3-alkyl / substituted alkyl / aryl(fluoroethyl)-1,3-thiazinane-2-ylidene)alkyl / arylformamides, characterized in that, It has the following structure (2): in, R 1 It is an alkyl group, a substituted alkyl group, or an aryl group; R 2 It is an alkyl group, a substituted alkyl group, an aryl group, or a heteroaryl group; R 3 It is hydrogen or alkyl; R 4 R 5 Each can be independently hydrogen, alkyl, alkyl with substituents, or aryl; R 6 It can be hydrogen, alkyl, alkyl with substituents, or aryl.

2. A method for synthesizing (Z)-N-(5-(fluoromethyl / 1-fluoroalkyl / fluoro(aryl)methyl)-3-alkyl / substituted alkyl / arylthiazolyl-2-methylene)-alkyl / arylformamide compounds and (Z)-N-(6-(fluoromethyl / 1-fluoroalkyl-3-alkyl / substituted alkyl / aryl(fluoroethyl)-1,3-thiazinane-2-methylene)alkyl / arylformamide compounds, characterized in that, include: The N-(high)allyl-N-(alkyl / substituted alkyl / aryl)aminethiocarboxyl)alkyl / aryl amide shown in formula (1), iodine (III) oxidant, and fluorine source are reacted in an organic solvent at room temperature to undergo a thiofluoroolefin bifunctionalization reaction to obtain the (Z)-N-(5-(fluoromethyl / 1-fluoroalkyl / fluoro(aryl)methyl)-3-alkyl / substituted alkyl / arylthiazolyl-2-methylene)-alkyl / aryl formamide compounds and (Z)-N-(6-(fluoromethyl / 1-fluoroalkyl-3-alkyl / substituted alkyl / aryl(fluoroethyl)-1,3-thiazinane-2-methylene)alkyl / aryl formamide compounds; the process is shown in reaction formula (I): in, R 1 It is an alkyl group, a substituted alkyl group, or an aryl group; R 2 It is an alkyl group, a substituted alkyl group, an aryl group, or a heteroaryl group; R 3 It is hydrogen or alkyl; R 4 R 5 Each can be independently hydrogen, alkyl, alkyl with substituents, or aryl; R 6 It can be hydrogen, alkyl, alkyl with substituents, or aryl.

3. A class of N-((2Z,5E)-5-(1-fluoroethylidene / 1-fluoroalkylene / 1-fluorosubstituted alkylene)-3-alkyl / substituted alkyl / arylthiazolyl-2-ylene)alkyl / arylamide compounds, characterized in that, It has the following structure (4): in, R 7 It is an alkyl group, a substituted alkyl group, or an aryl group; R 8 It is hydrogen or alkyl; R 9 It is an alkyl group or an alkyl group containing a substituent; R 10 It is an alkyl group, a substituted alkyl group, or an aryl group.

4. A method for synthesizing N-((2Z,5E)-5-(1-fluoroethylidene / 1-fluoroalkylene / 1-fluorosubstituted alkylene)-3-alkyl / substituted alkyl / arylthiazolyl-2-ylene)alkyl / arylamide compounds, characterized in that, include: The N-(high)propynyl-N-(alkyl / substituted alkyl / aryl)aminethioformyl)alkyl / aryl amide shown in formula (3), high-valent iodine(III) oxidant, and fluorine source are reacted in an organic solvent at room temperature to undergo a thiofluoroolefin bifunctionalization reaction to obtain the N-((2Z,5E)-5-(1-fluoroethylidene / 1-fluoroalkylidene / 1-fluorosubstituted alkylidene)-3-alkyl / substituted alkyl / arylthiazolyl-2-yl)alkyl / aryl amide compound. The process is shown in reaction formula (II). in, R 7 It is an alkyl group, a substituted alkyl group, or an aryl group; R 8 It is hydrogen or alkyl; R 9 It is an alkyl or substituted alkyl group; R 10 It is an alkyl group, a substituted alkyl group, or an aryl group.

5. A class of 5-(2-fluoroprop-2-yl / 2-fluorosubstituted alkyl / fluoromethyl / fluoro(aryl)methyl))thiazolyl-2-one compounds and 6-(2-fluoroprop-2-yl / 2-fluorosubstituted alkyl / fluoromethyl / fluoro(aryl)methyl))-1,3-thiazinyl-2-one compounds, characterized in that, It has the following structure (6): in, R 11 It is an alkyl group, a substituted alkyl group, or an aryl group; R 12 It is hydrogen or alkyl; R 13 It can be hydrogen, alkyl, substituted alkyl or aryl; R 14 R 15 Each can be independently hydrogen, alkyl, substituted alkyl or aryl.

6. A method for synthesizing 5-(2-fluoroprop-2-yl / 2-fluorosubstituted alkyl / fluoromethyl / fluoro(aryl)methyl))thiazolyl-2-one compounds and 6-(2-fluoroprop-2-yl / 2-fluorosubstituted alkyl / fluoromethyl / fluoro(aryl)methyl))-1,3-thiazinyl-2-one compounds, characterized in that, include: The ((high)allyl)(alkyl / substituted alkyl / aryl)amine thioformyl fluoride, high-valent iodine (III) oxidant, and fluorine source shown in formula (5) are subjected to a hydrolysis followed by a thiofluoroolefin bifunctionalization reaction at room temperature to obtain the 5-(2-fluoroprop-2-yl / 2-fluorosubstituted alkyl / fluoromethyl / fluoro(aryl)methyl))thiazolyl-2-one compounds and the 6-(2-fluoroprop-2-yl / 2-fluorosubstituted alkyl / fluoromethyl / fluoro(aryl)methyl))-1,3-thiazinane-2-one compounds; the process is shown in reaction formula (I, II): in, R 11 It is an alkyl group, a substituted alkyl group, or an aryl group; R 12 It is hydrogen or alkyl; R 13 It can be hydrogen, alkyl, substituted alkyl or aryl; R 14 R 15 Each can be independently hydrogen, alkyl, substituted alkyl, or aryl; The molar ratio of ((high)allyl)(alkyl / substituted alkyl / aryl)amine thioformyl fluoride shown in formula (5) to iodine (III) oxidant is 1:1-3; and / or, the molar ratio of ((high)allyl)(alkyl / substituted alkyl / aryl)amine thioformyl fluoride shown in formula (5) to fluorine source is 1:1-20.

7. The synthesis method according to claim 2, characterized in that, The molar ratio of N-(high)allyl-N-(alkyl / substituted alkyl / aryl)aminethiocarbamoyl)alkyl / aryl amide of formula (1) to iodine (III) oxidant is 1:1-3; and / or, the molar ratio of N-(high)allyl-N-(alkyl / substituted alkyl / aryl)aminethiocarbamoyl)alkyl / aryl amide of formula (1) to fluorine source is 1:1-20.

8. The synthesis method according to claim 4, characterized in that, The molar ratio of N-(high)propargyl-N-(alkyl / substituted alkyl / aryl)aminethioformyl)alkyl / aryl amide shown in formula (3) to high-valent iodine (III) oxidant is 1:1-3; and / or, the molar ratio of N-(high)propargyl-N-(alkyl / substituted alkyl / aryl)aminethioformyl)alkyl / aryl amide shown in formula (3) to fluorine source is 1:1-20.

9. The synthesis method according to any one of claims 2, 4, and 6, characterized in that, The high-valent iodine (III) oxidant is PhI(OPiv)2, PhI(OAc)2, or PhI(OAd)2; and / or, the fluorine source is Et3N·3HF or py·8HF; and / or, the organic solvent is acetonitrile, dichloromethane, toluene, 1,4-dioxane, diethyl ether, xylene, chlorobenzene, or trifluorotoluene; and / or, the reaction time is 1-8 hours; and / or, the method further includes post-treatment and column chromatography separation and purification steps, wherein the separation and purification is performed using a mixed solvent of petroleum ether and ethyl acetate as the eluent for column chromatography separation.

10. The (Z)-N-(5-(fluoromethyl / 1-fluoroalkyl / fluoro(aryl)methyl)-3-alkyl / substituted alkyl / arylthiazolyl-2-ylidene)-alkyl / arylformamides according to claim 1 and the (Z)-N-(6-(fluoromethyl / 1-fluoroalkyl-3-alkyl / substituted alkyl / aryl(fluoroethyl)-1,3-thiazinane-2-ylidene)alkyl / arylformamides, or the N-((2Z,5E)-5-(1-fluoroethylene / 1-fluoroalkylene / 1-fluorosubstituted alkylene)-3-alkyl / substituted alkyl / arylthiazolyl-2-ylidene)alkyl / arylformamides according to claim 3, or the 5-(2-fluoropropyl-2-yl / 2-fluorosubstituted alkyl / fluoromethyl / fluoro(aryl)methylene)alkyl / arylformamides according to claim 5. Applications of methyl thiazolidin-2-one compounds and 6-(2-fluoroprop-2-yl / 2-fluorosubstituted alkyl / fluoromethyl / fluoro(aryl)methyl)-1,3-thiazin-2-one compounds in the synthesis of other compounds and pharmaceutical intermediates; applications in the preparation of drugs with antitumor, antidepressant, antihypertensive, anti-inflammatory, anti-Alzheimer's disease, and insecticidal activities; applications as progesterone receptor binders in the preparation of drugs with antibacterial, antitumor, antioxidant, and antipyretic activities; applications as calcium channel regulators and cannabinoid receptor ligands in the preparation of anti-HIV, anticonvulsant, bactericidal, and insecticidal drugs; applications as EP4 agonists; and applications as prostaglandin E2 receptor subtypes in the preparation of drugs for treating glaucoma metabolism, diabetes, and fatty liver.

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