Benzothiazinone pyrazole derivative as well as preparation method and application thereof

Abstract

The invention relates to the technical field of compound synthesis and pesticides, in particular to benzothiazinone pyrazole derivatives as well as a preparation method and application thereof, and the general formula of the benzothiazinone pyrazole derivatives is as shown in formula I; the derivative has effective pre-emergence and post-emergence herbicidal activity, is high in safety to crops and can be applied to preparation of herbicides; the derivative is simple in structure and preparation process, low in production cost and wide in application prospect.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of compound synthesis, and particularly relates to a benzothiazinone pyrazole derivative, a preparation method and application thereof. BACKGROUND

[0002] Weed damage in farmland is one of the main biological disasters in agricultural production. Weeds compete with crops for growing space, sunlight and soil nutrients, resulting in significant losses in agricultural production. In addition, the increase in global population, climate change and the reduction in arable land have further exacerbated the global food shortage. Therefore, weed damage has become one of the important problems in the world's integrated weed management in agriculture. And herbicides are effective tools for controlling weeds, ensuring crop yields. So far, the main measures for controlling weeds include mechanical weeding, biological weeding and chemical weeding. Among them, chemical weeding is widely used because of its high efficiency, time-saving and labor-saving characteristics. Therefore, the development of new herbicides with broad-spectrum, high efficiency and low resistance risk is a necessary condition to achieve sustainable agricultural production and improve crop quality and yield.

[0003] In recent years, small molecules containing pyrazole units have been widely used in the fields of medicine, pesticide, material, etc. In the field of pesticides, pyrazole compounds exhibit diverse biological activities, such as antibacterial, antifungal, insecticidal, herbicidal, etc. Due to their high efficiency, low toxicity, low residue, broad spectrum and other advantages, they have become one of the hotspots in the research of green herbicides. Among them, herbicides that have been developed and marketed, such as benzofenap, pyrasulfotole, pyrazolynate, benzofluor, etc. all contain pyrazole active unit structure. Such herbicides have unique action mechanism, high herbicidal activity, good safety and low resistance risk, and are important herbicide choices in modern agriculture. Therefore, designing and synthesizing herbicidal small molecules based on pyrazole units is in line with the current trend of new pesticide creation. For example, CN113387926A discloses a heterocyclic carboxylic acid ester compound and its use as a herbicide. The compound of the invention contains a benzoyl group and a heterocyclic acyl group, has a novel structure, and has high herbicidal activity at a low dose. It is not only efficient, but also reduces the use of pesticides, reduces costs, and reduces environmental pollution. However, its crop safety is unknown. For another example, CN115215885A discloses a benzothiadiazinone compound, a preparation method and application thereof, discloses a compound containing benzothiadiazinone and pyrazole structure, and shows inhibition effect on the growth of weeds such as abutilon, eclipta, amaranthus, barnyard grass, crabgrass and goosegrass. However, the crop safety of the compound needs to be improved, and there are problems such as high production cost.

[0004] Therefore, it is still of great significance to find a herbicide with high herbicidal activity, excellent crop safety, low production cost and high yield. SUMMARY

[0005] The present application aims at the deficiencies of the prior art, and provides a benzothiazinone pyrazole derivative, a preparation method and application thereof.

[0006] Specifically, the technical scheme is implemented as follows: The first object of the present application is to provide a benzothiazinone pyrazole derivative, the structural general formula of the derivative being as shown in formula (I): In formula (I): R 1 is selected from H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy; R 2 , R 3 , R 4 are each independently selected from H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy; C3-C6 alkenyl, C3-C6 alkynyl; R 5 is H, C1-C6 alkylsulfonyl, C1-C6 haloalkyl, C1-C6 alkoxy, (C1-C4)alkoxy-(C1-C6)alkylsulfonyl or phenylsulfonyl, benzoyl, (C1-C4)alkylbenzoyl-(C1-C6)alkyl or benzyl, -CONR 6 R 7 , -SO2-Ar-R 8 , -C-CO-Ar-R 9 R 10 , 1-methylethyl ethyl carbonate, (ethoxycarbonyloxy)methyl, but-3-en-yl(1-chloroethyl) carbonate-methane; R 6 , R 7 , R 8 are each independently selected from C1-C6 alkyl; R 9 , R 10 are each independently selected from H, nitro, halogen, C1-C4 alkyl.

[0007] In formula (I), the dotted line represents that it can be a bond, and at the same time, only one can be a double bond, and further includes the following structural formula: Further, the benzothiazinone pyrazole derivative includes the following compounds: Compound A1: (4-ethoxy-1-methyl-2,2-dioxo-1H-benzo[c][1,2]thiazin-7-yl)(5-hydroxy-1,3-dimethyl-1H-pyrazol-4-yl)methanone; Compound A2: (5-hydroxy-l,3-dimethyl-lH-pyrazol-4-yl)(l-methyl-2,2-dioxo-4- propoxy-lH-benzo[c][l,2]thiazin-7-yl)methanone; Compound A3: (5-hydroxy-l,3-dimethyl-lH-pyrazol-4-yl)(l-methyl-2,2-dioxo-4- propoxy-3-propyl-lH-benzo[c][l,2]thiazin-7-yl)methanone; Compound A4: (4-ethoxy-3-ethyl-l-methyl-2,2-dioxo-lH-benzo[c][l,2]thiazin-7-yl)(5- hydroxy-l,3-dimethyl-lH-pyrazol-4-yl)methanone; Compound A5: 4-(4-ethoxy-l-methyl-2,2-dioxo-lH-benzo[c][l,2]thiazin-7- carbonyl)-l,3-dimethyl-lH-pyrazol-5-yl-4-methylbenzenesulfonate; Compound A6: 2-((4-(4-ethoxy-l-methyl-2,2-dioxo-lH-benzo[c][l,2]thiazin-7- carbonyl)-l,3-dimethyl-lH-pyrazol-5-yl)oxy)-l-(4-nitrophenyl)ethan-l-one; Compound A7: 2-((l,3-dimethyl-4-(l-methyl-2,2-dioxo-4-propoxy-lH- benzo[c][l,2]thiazin-7-carbonyl)-lH-pyrazol-5-yl)oxy)-l-(4-nitrophenyl)ethan-l-one; Compound A8: 2-((l,3-dimethyl-4-(l-methyl-2,2-dioxo-4-propoxy-3-propyl-lH- benzo[c][l,2]thiazin-7-carbonyl)-lH-pyrazol-5-yl)oxy)-l-(4-nitrophenyl)ethan-l-one; Compound B1: 7-(5-hydroxy-l,3-dimethyl-lH-pyrazole-4-carbonyl)-l-methyl- lH-benzo[c][l,2]thiazin-4(3H)-one-2,2-dioxide; Compound B2: 7-(5-hydroxy-l,3-dimethyl-lH-pyrazole-4-carbonyl)-l,3-dimethyl- lH-benzo[c][l,2]thiazin-4(3H)-one-2,2-dioxide; Compound B3: 7-(5-hydroxy-l,3-dimethyl-lH-pyrazole-4-carbonyl)-l,3,3-trimethyl- lH-benzo[c][l,2]thiazin-4(3H)-one-2,2-dioxide; Compound B4: 3,3-diallyl-7-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1- methyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide; Compound B5: 7-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1-methyl-3- (methylsulfonyl)-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide; Compound B6: 7-(1,3-dimethyl-5-(2-(4-nitrophenyl)-2-oxoethoxy)-1H-pyrazole-4- carbonyl)-1-methyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide; Compound B7: 4-(1,3-dimethyl-2,2-dioxo-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7- carbonyl)-1,3-dimethyl-1H-pyrazol-5-yl diethylcarbamate; Compound B8: 4-(1,3-dimethyl-2,2-dioxo-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7- carbonyl)-1,3-dimethyl-1H-pyrazol-5-yl 4-methylbenzenesulfonate; Compound B9: 1,3-dimethyl-4-(1,3,3-trimethyl-2,2-dioxo-4-oxo-3,4-dihydro-1H- benzo[c][1,2]thiazine-7-carbonyl)-1H-pyrazol-5-yl 4-methylbenzenesulfonate; Compound B10: 7-(1,3-dimethyl-5-(2-(4-nitrophenyl)-2-oxoethoxy)-1H-pyrazole-4- carbonyl)-1,3,3-trimethyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide; Compound B11: 1-((1,3-dimethyl-4-(1,3,3-trimethyl-2,2-dioxo-4-oxo-3,4-dihydro-1H- benzo[c][1,2]thiazine-7-carbonyl)-1H-pyrazol-5-yl)oxy)ethyl ethyl carbonate; Compound B12: 7-(5-(2-(2-fluorophenyl)-2-oxoethoxy)-1,3-dimethyl-1H-pyrazole-4- carbonyl)-1,3,3-trimethyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide; Compound B13: 7-(5-(2-(2,4-difluorophenyl)-2-oxoethoxy)-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1,3,3-trimethyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide; Compound B14: (1,3-dimethyl-4-(1,3,3-trimethyl-2,2-dioxo-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carbonyl)-1H-pyrazol-5-yl)oxy)methyl ethyl carbonate; Compound B15: 3-en-1-yl(1-((1,3-dimethyl-4-(1,3,3-trimethyl-2,2-dioxo-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carbonyl)-1H-pyrazol-5-yl)oxy)ethyl) carbonate; Compound B16: 7-(5-(2-(4-methoxyphenyl)-2-oxoethoxy)-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1,3,3-trimethyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide; Compound B17: 3,3-diallyl-7-(1,3-dimethyl-5-(2-(4-nitrophenyl)-2-oxoethoxy)-1H-pyrazole-4-carbonyl)-1-methyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide; Compound B18: 1-((4-(3,3-diallyl-1-methyl-2,2-dioxo-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carbonyl)-1,3-dimethyl-1H-pyrazol-5-yl)oxy)ethyl carbonate.

[0008] The first objective of this invention is to provide a method for preparing the aforementioned benzothiazinone pyrazole derivatives, comprising the following steps: (1) Preparation of intermediate 1: Dimethyl aminoterephthalate and triethylamine were added to dichloromethane (DCM), and the mixture was reacted at room temperature for 30 minutes. Then, methanesulfonic anhydride was added and the reaction was carried out at room temperature. After the reaction was completed, the mixture was extracted with water and ethyl acetate, concentrated under reduced pressure, dried and subjected to column chromatography to obtain intermediate 1. (2) Preparation of intermediate 2: Intermediate 1 was dissolved in DMF solution, cesium carbonate was added at room temperature and stirred for 30 minutes; then iodomethane was added and the reaction was stirred continuously at room temperature for 5 hours; after the reaction was complete, dilute hydrochloric acid solution was added and the pH of the mixture was adjusted to about 7. Then, it was extracted with water and ethyl acetate, concentrated under reduced pressure, dried and subjected to column chromatography to obtain intermediate 2. (3) Preparation of intermediate 3: Intermediate 2 was dissolved in DMF solution, and NaH was added under ice bath conditions and stirred continuously until the mixture was homogeneous. The mixture was reacted at room temperature for 3 hours. After the reaction was completed, dilute hydrochloric acid solution was added and the pH of the mixture was adjusted to about 7. The mixture was then extracted with a large amount of water and ethyl acetate, concentrated under reduced pressure, dried and subjected to column chromatography to obtain intermediate 3. (4) Preparation of intermediate 4a-4h: Intermediate 3 was stirred and mixed at room temperature for 30 minutes under the conditions of Cs2CO3 and DMF as catalyst and solvent, and then a haloalkane or methanesulfonic anhydride was added and the temperature was raised to 80℃ for 7-8 h. After the reaction was completed, dilute hydrochloric acid solution was added to adjust the pH, and then the mixture was extracted, concentrated under reduced pressure and dried. Intermediate 4a-4h was obtained by column chromatography eluting with petroleum ether and ethyl acetate. (5) Preparation of intermediates 5a-5i: Intermediate 4a-4h, lithium hydroxide, and 80% methanol solution were mixed and stirred. The mixture was stirred continuously at room temperature for 6 hours. After the reaction was complete, the reaction solution was poured into ice water. Then, dilute hydrochloric acid solution was added while stirring. When the pH of the mixture was adjusted to 2-3, a solid precipitated out. The solid was obtained by filtration and dried in vacuum to obtain intermediate 5a-5i. (6) Preparation of intermediates 6a-6i: Dissolve 5a-5i in dry dichloromethane, then add triethylamine and 2-chloro-1-methylpyridine iodide (CMPI), and stir continuously until homogeneous. Then add 1,3-dimethyl-5-pyrazolone and triethylamine at room temperature, allowing the reaction system to react for 10-12 hours at room temperature. After the reaction is complete, wash with saturated sodium bicarbonate solution, dry with anhydrous sodium sulfate, and recrystallize to obtain 1,3-dimethyl-1 H -Pyrazole-5-dimethyl-substituted benzothiazide ketone carboxylate, namely intermediate 6a-6i; (7) Preparation of benzothiazinone pyrazole derivatives of the target compound: Intermediate 6a-6i was dissolved in acetonitrile, and then triethylamine and acetone cyanohydrin were added. The reaction was carried out at room temperature for 12-14 hours, and the extent of the reaction was monitored by TLC. After the reaction was completed, the solvent was evaporated under vacuum, the pH was adjusted with dilute hydrochloric acid solution, and the product was extracted with ethyl acetate and washed with saturated NaCl. Finally, the crude product was subjected to column chromatography on silica gel using a dichloromethane / methanol gradient system to obtain benzoylpyrazole derivatives.

[0009] (8) Preparation of the target compound containing benzothiazinone pyrazole derivatives: A portion of the target compound obtained above was mixed with potassium carbonate in acetonitrile solution. Various substituted halides were added at room temperature, and the reaction system was heated to 85°C for reflux reaction. After the reaction was complete, the system was concentrated under reduced pressure, extracted and purified by column chromatography to obtain another portion of pyrazole derivatives containing thiamethoxamone.

[0010] In step (1), the amounts of dimethyl terephthalate, triethylamine, and methanesulfonic anhydride are calculated in the following molar ratio: dimethyl terephthalate: triethylamine: methanesulfonic anhydride = 1:1.5:1.2; the amount of DCM is controlled by adding 1 mL of DCM per millimol of dimethyl terephthalate.

[0011] In step (2), the amounts of intermediate 1, cesium carbonate, and iodomethane are calculated in the following molar ratio: intermediate 1: cesium carbonate: iodomethane = 1: 1.5: 1.2; the amount of DMF is controlled by adding 1 mL of DMF per millimol of intermediate 1.

[0012] In step (3), the amount of intermediate 2 and NaH is calculated in molar ratio as follows: intermediate 2: NaH = 1:1.5; the amount of DMF is controlled by adding 1 mL of DMF per millimol of intermediate 2.

[0013] In step (4), the amounts of intermediate 3, cesium carbonate, and haloalkanes or sulfonic acid derivatives are in the following molar ratio: intermediate 3: cesium carbonate: haloalkanes = 1:1.5:1.5; the amount of DMF is controlled by adding 1 mL of dichloromethane per millimol of intermediate 3.

[0014] The halogenated hydrocarbons mentioned are: bromoethane, bromopropane, iodomethane, and 3-bromopropane. The sulfonic acid derivative: methanesulfonic anhydride In step (5), the amount of intermediate 4a-4h and lithium hydroxide is calculated in molar ratio as follows: intermediate 4a-4h: lithium hydroxide = 1:2; the amount of 80% methanol is controlled by adding 1 mL of 80% methanol per millimol of intermediate 4a-4h.

[0015] In step (6), the amounts of intermediate 5a-5i, 1,3-dimethyl-5-pyrazolone, triethylamine, and CMPI are calculated in the following molar ratio: intermediate 5a-5i: 1,3-dimethyl-5-pyrazolone: ​​triethylamine: CMPI = 1:1.25:2:1.25; the amount of dichloromethane is controlled by adding 1 mL of dichloromethane per millimol of intermediate 5a-5i.

[0016] In step (7), the amounts of intermediate 6a-6i, triethylamine, and acetone cyanohydrin are calculated in the following molar ratio: intermediate 6a-6i: triethylamine: acetone cyanohydrin = 1:1.5:0.1; the amount of acetonitrile is controlled by adding 1 mL of acetonitrile per millimol of intermediate 6a-6i.

[0017] In step (8), the amounts of the target compound, potassium carbonate, and various substituted halides are calculated in the following molar ratio: target compound: potassium carbonate: various substituted halides = 1:1.5:1.2; the amount of acetonitrile is controlled by adding 1 mL of acetonitrile to every millimole of the target compound.

[0018] The various substituted halides are any one of 2-bromo-1-(4-nitrophenyl)ethane-1-one, diethylcarbamate, p-methylbenzenesulfonyl chloride, 1-chloroethyl ethyl carbonate, 2-bromo-1-(2-fluorophenyl)ethane-1-one, 2-bromo-1-(2,4-difluorophenyl)ethane-1-one, chloromethylethyl carbonate, 3-buten-1-ynyl carbonate (1-chloroethyl) ester, and 2-bromo-1-(4-methoxyphenyl)ethane-1-one.

[0019] The preparation route of the benzothiazide pyrazole derivative is any one of the following: Route 1: Route 2: A third object of the present invention is to provide the use of the benzothiazide pyrazole derivative in the preparation of herbicides or weed growth enzyme inhibitors.

[0020] Specifically, the weeds are goosegrass, barnyard grass, velvetleaf, amaranth, purslane, and foxtail grass.

[0021] Beneficial effects: This invention optimizes and derives pyrazole-based herbicides based on the structure of benzothiazide pyrazoles to create small molecules of pyrazole herbicides with relatively stable physicochemical properties and excellent drug-like properties. These derivatives are particularly effective in post-emergence inhibition of barnyard grass, goosegrass, foxtail grass, velvetleaf, amaranth, and purslane.

[0022] The pre-emergence herbicidal activity tests showed that compounds A3 and B18, at a concentration of 100 μg / mL, exhibited over 80% inhibition of the roots and stems of *Portulaca oleracea*. Compounds A7, B4, B11, B12, and B13, at a concentration of 100 μg / mL, showed over 80% inhibition of *Echinochloa crus-galli* roots. Post-emergence herbicidal activity tests, at a dose of 300 g ai / ha, compounds B4, B10, and B16 showed 100% herbicidal activity against *Amaranthus retroflexus*, *Portulaca oleracea*, and *Abutilon theophrasti*, and also over 80% herbicidal activity against monocotyledonous weeds such as *Echinochloa crus-galli*, *Setaria viridis*, and *Eleusine indica*. At 150 g ai / ha, compounds B3, B10, B13, B14, B16, and B18 also showed 100% inhibition of *Amaranthus retroflexus*, *Portulaca oleracea*, and *Abutilon theophrasti*. In particular, compound B10 still maintains 100% herbicidal activity against goosegrass, amaranth, purslane, and velvetleaf at 75 ga.i. / ha.

[0023] The benzoylpyrazole derivatives designed and synthesized in this invention have simple structures, simple preparation processes, low production costs, high yields, and great application prospects. Attached Figure Description

[0024] Figure 1 The diagram shows the preparation routes of the benzoylpyrazole derivatives in Examples 1-8.

[0025] Figure 2 The above are the synthetic routes for the compounds in Examples 9-26. Detailed Implementation

[0026] The specific embodiments of the present invention will be described in further detail below, but the present invention is not limited to these embodiments. Any improvements or substitutions based on the basic spirit of these embodiments shall still fall within the scope of protection claimed by the claims of the present invention.

[0027] Example 1: A method for preparing (4-ethoxy-1-methyl-2,2-dioxo-1H-benzo[c][1,2]thiazin-7-yl)(5-hydroxy-1,3-dimethyl-1H-pyrazol-4-yl) methyl ketone (i.e., compound A1), comprising the following steps: (1) Preparation of 2-(methanesulfonamide)dimethyl terephthalate: Dimethyl terephthalate (10.00 g, 47.80 mmol) was dissolved in 150 mL of DCM, followed by the addition of triethylamine (7.26 g, 71.70 mmol). The reaction was carried out at room temperature for 30 minutes, and then methanesulfonic anhydride (9.99 g, 57.36 mmol) was slowly added. The reaction mixture was allowed to react at room temperature for 5 hours. After the reaction was complete, the mixture was extracted with water and ethyl acetate, concentrated under reduced pressure, dried, and subjected to column chromatography to obtain 10.12 g of solid 2-(methanesulfonamide)dimethyl terephthalate intermediate, with a yield of 73.70%.

[0028] (2) Preparation of 2-(N-methylmethanesulfonamide)dimethyl terephthalate: Dimethyl terephthalate (10.12 g, 35.23 mmol) was dissolved in 100 mL of DMF, followed by the addition of cesium carbonate (17.22 g, 52.84 mmol). The mixture was stirred at room temperature for 30 minutes, and then iodomethane (6.00 g, 42.27 mmol) was slowly added. The mixture was stirred continuously at room temperature for 5 hours. After the reaction was complete, dilute hydrochloric acid solution was added to adjust the pH of the mixture to about 7. The mixture was then extracted with water and ethyl acetate. After concentration under reduced pressure, drying, and column chromatography, 7.86 g of 2-(N-methylmethanesulfonamide)dimethyl terephthalate intermediate was obtained, with a yield of 74.08%.

[0029] (3) Preparation of methyl-1-methyl-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carboxylic acid ester-2,2-dioxide: 2-(N-methylmethanesulfonamide)dimethyl terephthalate (7.86 g, 26.09 mmol) was dissolved in 80 mL of DMF, and NaH (1.25 g, 52.17 mmol) was slowly added under ice bath conditions. The reaction was carried out at room temperature for 3 hours. After the reaction was completed, dilute hydrochloric acid solution was added to adjust the pH of the mixture to about 7. The mixture was then extracted with a large amount of water and ethyl acetate. After concentration under reduced pressure, drying, and column chromatography, 6.05 g of methyl-1-methyl-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carboxylic acid ester-2,2-dioxide intermediate was obtained, with a yield of 86.18%.

[0030] (4) Preparation of methyl-4-ethoxy-1-methyl-1H-benzo[c][1,2]thiazine-7-carboxylic acid ester-2,2-dioxide: 6.05 g (22.47 mmol) of methyl-1-methyl-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carboxylate-2,2-dioxide was dissolved in 60 mL of DMF, followed by the addition of 10.98 g (33.70 mmol) of cesium carbonate. The mixture was stirred at room temperature for 30 minutes, and then 2.94 g (26.96 mmol) of bromoethane was slowly added. The mixture was heated to 80 °C and reacted for 7–8 h. After the reaction was complete, the pH was adjusted with dilute hydrochloric acid, followed by extraction, concentration under reduced pressure, and drying. 4.51 g of the intermediate methyl-4-ethoxy-1-methyl-1H-benzo[c][1,2]thiazine-7-carboxylate-2,2-dioxide was obtained by column chromatography eluting with petroleum ether and ethyl acetate, yielding 67.51%.

[0031] (5) Preparation of 4-ethoxy-1-methyl-1H-benzo[c][1,2]thiazine-7-carboxylic acid-2,2-dioxide: 4.51 g (15.17 mmol) of methyl-4-ethoxy-1-methyl-1H-benzo[c][1,2]thiazine-7-carboxylic acid ester-2,2-dioxide, 0.73 g (30.34 mmol) of LiOH and 80% MeOH (50 mL) were mixed and stirred. The mixture was stirred continuously at room temperature for 6 hours. After the reaction was complete, the reaction solution was poured into ice water, and then dilute hydrochloric acid solution was added with stirring. When the pH of the mixture was adjusted to 2-3, a solid precipitated out. After filtration and drying under vacuum, 4.12 g of 4-ethoxy-1-methyl-1H-benzo[c][1,2]thiazine-7-carboxylic acid-2,2-dioxide intermediate was obtained, with a yield of 95.8%.

[0032] (6) Preparation of 2,2-dioxide of 1,3-dimethyl-1H-pyrazol-5-yl-4-ethoxy-1-methyl-1H-benzo[c][1,2]thiazine-7-carboxylate: 4-Ethoxy-1-methyl-1H-benzo[c][1,2]thiazine-7-carboxylic acid 2,2-dioxide (4.12 g, 14.54 mmol) was dissolved in dry dichloromethane. Then, Et3N (2.94 g, 29.09 mmol) and CMPI (4.64 g, 18.18 mmol) were added, and the mixture was stirred continuously for a period of time. Finally, 1,3-dimethyl-5-pyrazolone (2.04 g, 18.18 mmol) and Et3N (2.94 g, 29.09 mmol) were added at room temperature. The reaction system was allowed to react at room temperature for 10-12 hours. After the reaction was complete, the mixture was washed with saturated sodium bicarbonate solution, dried with anhydrous sodium sulfate, and recrystallized to obtain 3.42 g of 1,3-dimethyl-1H-pyrazol-5-yl-4-ethoxy-1-methyl-1H-benzo[c][1,2]thiazine-7-carboxylic acid ester-2,2-dioxide intermediate, with a yield of 62.29%.

[0033] (7) Preparation of (4-ethoxy-1-methyl-2,2-dioxo-1H-benzo[c][1,2]thiazin-7-yl)(5-hydroxy-1,3-dimethyl-1H-pyrazol-4-yl) methyl ketone (i.e., compound A1): Dissolve 1,3-dimethyl-1H-pyrazol-5-yl-4-ethoxy-1-methyl-1H-benzo[c][1,2]thiazine-7-carboxylic acid ester-2,2-dioxide (3.42 g, 9.06 mmol) in 35 mL of acetonitrile, then add Et3N (1.38 g, 13.59 mmol) and acetone cyanohydrin (77.12 mg, 0.91 mmol). After reacting at room temperature for 12-14 h, the extent of the reaction was monitored by TLC. After the reaction was complete, the solvent was evaporated under vacuum, the pH was adjusted with dilute hydrochloric acid solution, and the product was extracted with ethyl acetate, followed by washing with saturated NaCl. Finally, the crude product was subjected to column chromatography on silica gel using a dichloromethane / methanol gradient system to obtain 1.12 g of (4-ethoxy-1-methyl-2,2-dioxo-1H-benzo[c][1,2]thiazin-7-yl)(5-hydroxy-1,3-dimethyl-1H-pyrazol-4-yl) methyl ketone, with a yield of 32.75%.

[0034] Example 2: A method for preparing (5-hydroxy-1,3-dimethyl-1H-pyrazol-4-yl)(1-methyl-2,2-dioxo-4-propoxy-1H-benzo[c][1,2]thiazin-7-yl) methyl ketone (i.e., compound A2), comprising the following steps: Steps (1)-(3): Refer to steps (1)-(3) of Example 1; Step (4): Referring to step (4) of Example 1, replace bromoethane with bromopropane; Step (5): Referring to step (5) of Example 1, methyl-4-ethoxy-1-methyl-1H-benzo[c][1,2]thiazine-7-carboxylate-2,2-dioxide is replaced with methyl-1-methyl-4-propoxy-1H-benzo[c][1,2]thiazine-7-carboxylate-2,2-dioxide; Step (6): Referring to step (6) of Example 1, 4-ethoxy-1-methyl-1H-benzo[c][1,2]thiazine-7-carboxylic acid-2,2-dioxide is replaced with 1-methyl-4-propoxy-1H-benzo[c][1,2]thiazine-7-carboxylic acid-2,2-dioxide; Step (7): Preparation of (5-hydroxy-1,3-dimethyl-1H-pyrazol-4-yl)(1-methyl-2,2-dioxo-4-propoxy-1H-benzo[c][1,2]thiazin-7-yl) methyl ketone (i.e., compound A2): Dissolve 1,3-dimethyl-1H-pyrazol-5-yl-1-methyl-4-propoxy-1H-benzo[c][1,2]thiazine-7-carboxylate-2,2-dioxide (800.00 mg, 2.04 mmol) in 80 mL of acetonitrile, then add Et3N (310.22 mg, 3.07 mmol) and acetone cyanohydrin (17.39 mg, 0.20 mmol). After reacting at room temperature for 12-14 h, the extent of the reaction was monitored by TLC. After the reaction was complete, the solvent was evaporated under vacuum, the pH was adjusted with dilute hydrochloric acid solution, and the mixture was extracted with ethyl acetate and washed with saturated NaCl. Finally, the crude substance was subjected to column chromatography on silica gel using a dichloromethane / methanol gradient system to obtain 0.42 g of (5-hydroxy-1,3-dimethyl-1H-pyrazol-4-yl)(1-methyl-2,2-dioxo-4-propoxy-1H-benzo[c][1,2]thiazin-7-yl) methyl ketone, with a yield of 52.50%.

[0035] Example 3: A method for preparing (5-hydroxy-1,3-dimethyl-1H-pyrazol-4-yl)(1-methyl-2,2-dioxo-4-propoxy-3-propyl-1H-benzo[c][1,2]thiazin-7-yl) methyl ketone (i.e., compound A3), comprising the following steps: Steps (1)-(4): Refer to steps (1)-(4) of Example 2; Step (5): Referring to step (5) of Example 1, methyl-4-ethoxy-1-methyl-1H-benzo[c][1,2]thiazine-7-carboxylate-2,2-dioxide is replaced with methyl-1-methyl-4-propoxy-3-propyl-1H-benzo[c][1,2]thiazine-7-carboxylate-2,2-dioxide; Step (6): Referring to step (6) of Example 1, 4-ethoxy-1-methyl-1H-benzo[c][1,2]thiazine-7-carboxylic acid-2,2-dioxide is replaced with 1-methyl-4-propoxy-3-propyl-1H-benzo[c][1,2]thiazine-7-carboxylic acid-2,2-dioxide; Step (7): Preparation of (5-hydroxy-1,3-dimethyl-1H-pyrazol-4-yl)(1-methyl-2,2-dioxo-4-propoxy-3-propyl-1H-benzo[c][1,2]thiazin-7-yl) methyl ketone (i.e., compound A3): Dissolve 1,3-dimethyl-1H-pyrazol-5-yl-1-methyl-4-propoxy-3-propyl-1H-benzo[c][1,2]thiazine-7-carboxylic acid ester-2,2-dioxide (1.00 g, 2.31 mmol) in 100 mL of acetonitrile, then add Et3N (350.13 mg, 3.46 mmol) and acetone cyanohydrin (19.63 mg, 0.23 mmol). After reacting at room temperature for 12-14 h, the extent of the reaction was monitored by TLC. After the reaction was complete, the solvent was evaporated under vacuum, the pH was adjusted with dilute hydrochloric acid solution, and the mixture was extracted with ethyl acetate, followed by washing with saturated NaCl. Finally, the crude substance was subjected to column chromatography on silica gel using a dichloromethane / methanol gradient system to obtain 0.50 g of (5-hydroxy-1,3-dimethyl-1H-pyrazol-4-yl)(1-methyl-2,2-dioxo-4-propoxy-3-propyl-1H-benzo[c][1,2]thiazin-7-yl) methyl ketone, with a yield of 50.00%.

[0036] Example 4: A method for preparing (4-ethoxy-3-ethyl-1-methyl-2,2-dioxo-1H-benzo[c][1,2]thiazin-7-yl)(5-hydroxy-1,3-dimethyl-1H-pyrazol-4-yl) methyl ketone (i.e., compound A4), comprising the following steps: Steps (1)-(4): Refer to steps (1)-(4) of Example 1; Step (5): Referring to step (5) of Example 1, methyl 4-ethoxy-1-methyl-1H-benzo[c][1,2]thiazine-7-carboxylate-2,2-dioxide is replaced with methyl 4-ethoxy-3-ethyl-1-methyl-1H-benzo[c][1,2]thiazine-7-carboxylate-2,2-dioxide; Step (6): Referring to step (6) of Example 1, 4-ethoxy-1-methyl-1H-benzo[c][1,2]thiazine-7-carboxylic acid-2,2-dioxide is replaced with 4-ethoxy-3-ethyl-1-methyl-1H-benzo[c][1,2]thiazine-7-carboxylic acid-2,2-dioxide; Step (7): Preparation of (4-ethoxy-3-ethyl-1-methyl-2,2-dioxo-1H-benzo[c][1,2]thiazin-7-yl)(5-hydroxy-1,3-dimethyl-1H-pyrazol-4-yl) methyl ketone (i.e., compound A4): Dissolve 1,3-dimethyl-1H-pyrazol-5-yl-4-ethoxy-3-ethyl-1-methyl-1H-benzo[c][1,2]thiazine-7-carboxylic acid ester 2,2-dioxide (700.00 mg, 1.73 mmol) in 70 mL of acetonitrile, then add Et3N (262.05 mg, 2.59 mmol) and acetone cyanohydrin (14.69 mg, 0.17 mmol). After reacting at room temperature for 12-14 h, the extent of the reaction was monitored by TLC. After the reaction was complete, the solvent was evaporated under vacuum, the pH was adjusted with dilute hydrochloric acid solution, and the product was extracted with ethyl acetate, followed by washing with saturated NaCl. Finally, the crude product was subjected to column chromatography on silica gel using a dichloromethane / methanol gradient system to obtain 0.34 g of (4-ethoxy-3-ethyl-1-methyl-2,2-dioxo-1H-benzo[c][1,2]thiazin-7-yl)(5-hydroxy-1,3-dimethyl-1H-pyrazol-4-yl) methyl ketone, with a yield of 48.57%.

[0037] Example 5: A method for preparing 4-(4-ethoxy-1-methyl-2,2-dioxo-1H-benzo[c][1,2]thiazine-7-carbonyl)-1,3-dimethyl-1H-pyrazole-5-yl-4-methylbenzenesulfonate (i.e., compound A5), comprising the following steps: Steps (1)-(7): Refer to steps (1)-(7) of Example 1; Step (8): Preparation of 4-(4-ethoxy-1-methyl-2,2-dioxo-1H-benzo[c][1,2]thiazine-7-carbonyl)-1,3-dimethyl-1H-pyrazole-5-yl 4-methylbenzenesulfonate (i.e., compound A5): (4-ethoxy-1-methyl-2,2-dioxo-1H-benzo[c][1,2]thiazin-7-yl)(5-hydroxy-1,3-dimethyl-1H-pyrazol-4-yl) methyl ketone (400.00 mg, 1.06 mmol) was dissolved in 40 mL of acetonitrile, and then potassium carbonate (219.71 mg, 1.59 mmol) was added. After stirring at room temperature for half an hour, p-toluenesulfonyl chloride (242.46 mg, 1.27 mmol) was added. The reaction system was heated to 85 °C and refluxed. After the reaction was complete, the system was concentrated under reduced pressure, extracted and purified by column chromatography to obtain 0.41 g of 4-(4-ethoxy-1-methyl-2,2-dioxo-1H-benzo[c][1,2]thiazin-7-carbonyl)-1,3-dimethyl-1H-pyrazol-5-yl-4-methylbenzenesulfonate, with a yield of 72.77%.

[0038] Example 6: A method for preparing 2-((4-(4-ethoxy-1-methyl-2,2-dioxo-1H-benzo[c][1,2]thiazine-7-carbonyl)-1,3-dimethyl-1H-pyrazol-5-yl)oxy)-1-(4-nitrophenyl)ethane-1-one (i.e., compound A6), comprising the following steps: Steps (1)-(7): Refer to steps (1)-(7) of Example 1; Step (8): Preparation of 2-((4-(4-ethoxy-1-methyl-2,2-dioxo-1H-benzo[c][1,2]thiazine-7-carbonyl)-1,3-dimethyl-1H-pyrazol-5-yl)oxy)-1-(4-nitrophenyl)ethane-1-one (i.e., compound A6): Dissolve 400.00 mg (1.06 mmol) of (4-ethoxy-1-methyl-2,2-dioxo-1H-benzo[c][1,2]thiazin-7-yl)(5-hydroxy-1,3-dimethyl-1H-pyrazol-4-yl) methyl ketone in 40 mL of acetonitrile, then add potassium carbonate (219.71 mg, 1.59 mmol). After stirring at room temperature for half an hour, add 310.38 mg (1.27 mmol) of 2-bromo-1-(4-nitrophenyl)ethane-1-one. Heat the reaction system to 85 °C. The reaction was carried out under reflux at ℃. After the reaction was completed, the system was concentrated under reduced pressure, extracted and purified by column chromatography to obtain 0.39 g of 2-((4-(4-ethoxy-1-methyl-2,2-dioxo-1H-benzo[c][1,2]thiazine-7-carbonyl)-1,3-dimethyl-1H-pyrazol-5-yl)oxy)-1-(4-nitrophenyl)ethane-1-one, with a yield of 69.35%.

[0039] Example 7: A method for preparing 2-((1,3-dimethyl-4-(1-methyl-2,2-dioxo-4-propoxy-1H-benzo[c][1,2]thiazine-7-carbonyl)-1H-pyrazol-5-yl)oxy)-1-(4-nitrophenyl)ethane-1-one (i.e., compound A7), comprising the following steps: Steps (1)-(7): Refer to steps (1)-(7) of Example 2; Step (8): Preparation of 2-((1,3-dimethyl-4-(1-methyl-2,2-dioxo-4-propoxy-1H-benzo[c][1,2]thiazine-7-carbonyl)-1H-pyrazol-5-yl)oxy)-1-(4-nitrophenyl)ethane-1-one (i.e., compound A7) Dissolve (5-hydroxy-1,3-dimethyl-1H-pyrazol-4-yl)(1-methyl-2,2-dioxo-4-propoxy-1H-benzo[c][1,2]thiazin-7-yl) methyl ketone (420.00 mg, 1.07 mmol) in 45 mL of acetonitrile, then add potassium carbonate (222.43 mg, 1.61 mmol). After stirring at room temperature for half an hour, add 2-bromo-1-(4-nitrophenyl)ethane-1-one (314.22 mg, 1.29 mmol). Heat the reaction system to 85 °C. The reaction was carried out under reflux at ℃. After the reaction was completed, the system was concentrated under reduced pressure, extracted and purified by column chromatography to obtain 0.31 g of 2-((1,3-dimethyl-4-(1-methyl-2,2-dioxo-4-propoxy-1H-benzo[c][1,2]thiazine-7-carbonyl)-1H-pyrazol-5-yl)oxy)-1-(4-nitrophenyl)ethane-1-one, with a yield of 52.10%.

[0040] Example 8: A method for preparing 2-((1,3-dimethyl-4-(1-methyl-2,2-dioxo-4-propoxy-3-propyl-1H-benzo[c][1,2]thiazine-7-carbonyl)-1H-pyrazol-5-yl)oxy)-1-(4-nitrophenyl)ethane-1-one (i.e., compound A8), comprising the following steps: Steps (1)-(7): Refer to steps (1)-(7) of Example 3; Step (8): Preparation of 2-((1,3-dimethyl-4-(1-methyl-2,2-dioxo-4-propoxy-3-propyl-1H-benzo[c][1,2]thiazine-7-carbonyl)-1H-pyrazol-5-yl)oxy)-1-(4-nitrophenyl)ethane-1-one (i.e., compound A8): Dissolve 500.00 mg (1.15 mmol) of (5-hydroxy-1,3-dimethyl-1H-pyrazol-4-yl)(1-methyl-2,2-dioxo-4-propoxy-3-propyl-1H-benzo[c][1,2]thiazin-7-yl) methyl ketone in 50 mL of acetonitrile, then add potassium carbonate (239.10 mg, 1.73 mmol). After stirring at room temperature for half an hour, add 2-bromo-1-(4-nitrophenyl)ethane-1-one (337.76 mg, 1.38 mmol). Heat the reaction system to 85 °C. The reaction was carried out under reflux at ℃. After the reaction was completed, the system was concentrated under reduced pressure, extracted and purified by column chromatography to obtain 0.44 g of 2-((1,3-dimethyl-4-(1-methyl-2,2-dioxo-4-propoxy-3-propyl-1H-benzo[c][1,2]thiazine-7-carbonyl)-1H-pyrazol-5-yl)oxy)-1-(4-nitrophenyl)ethane-1-one, with a yield of 63.93%.

[0041] Example 9: A method for preparing 7-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1-methyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide (i.e., compound B1), comprising the following steps: Steps (1)-(3): Refer to steps (1)-(3) of Example 1; Step (4): Referring to step (5) of Example 1, methyl 4-ethoxy-1-methyl-1H-benzo[c][1,2]thiazine-7-carboxylate 2,2-dioxide is replaced with methyl 1-methyl-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carboxylate 2,2-dioxide; Step (5): Referring to step (6) of Example 1, 4-ethoxy-1-methyl-1H-benzo[c][1,2]thiazine-7-carboxylic acid 2,2-dioxide is replaced with 1-methyl-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carboxylic acid 2,2-dioxide; Step (6): Preparation of 7-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1-methyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide (i.e., compound B1): Dissolve 1,3-dimethyl-1H-pyrazol-5-yl-1-methyl-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carboxylic acid ester 2,2-dioxide (600.00 mg, 1.72 mmol) in 60 mL of acetonitrile, then add Et3N (260.69 mg, 2.58 mmol) and acetone cyanohydrin (14.62 mg, 0.17 mmol). After reacting at room temperature for 12-14 h, the extent of the reaction was monitored by TLC. After the reaction was completed, the solvent was evaporated under vacuum, the pH was adjusted with dilute hydrochloric acid solution, and the product was extracted with ethyl acetate and washed with saturated NaCl. Finally, the crude product was subjected to column chromatography on silica gel using a dichloromethane / methanol gradient system to obtain 0.24 g of 7-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1-methyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide, with a yield of 40.00%.

[0042] Example 10: A method for preparing 7-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1,3-dimethyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide (i.e., compound B2), comprising the following steps: Steps (1)-(3): Refer to steps (1)-(3) of Example 1; Step (4): Referring to step (4) of Example 1, replace bromoethane with iodomethane; Step (5): Referring to step (5) of Example 1, methyl 4-ethoxy-1-methyl-1H-benzo[c][1,2]thiazine-7-carboxylate 2,2-dioxide is replaced with methyl 1,3-dimethyl-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carboxylate 2,2-dioxide; Step (6): Referring to step (6) of Example 1, 4-ethoxy-1-methyl-1H-benzo[c][1,2]thiazine-7-carboxylic acid 2,2-dioxide is replaced with 1,3-dimethyl-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carboxylic acid 2,2-dioxide; Step (7): Preparation of 7-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1,3-dimethyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide (i.e., compound B2): Dissolve 1,3-dimethyl-1H-pyrazol-5-yl1,3-dimethyl-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carboxylic acid ester 2,2-dioxide (800.00 mg, 2.20 mmol) in 80 mL of acetonitrile, then add Et3N (334.17 mg, 3.30 mmol) and acetone cyanohydrin (18.74 mg, 0.22 mmol). After reacting at room temperature for 12-14 h, the extent of the reaction was monitored by TLC. After the reaction was completed, the solvent was evaporated under vacuum, the pH was adjusted with dilute hydrochloric acid solution, and the product was extracted with ethyl acetate, followed by washing with saturated NaCl. Finally, the crude product was subjected to column chromatography on silica gel using a dichloromethane / methanol gradient system to obtain 0.35 g of 7-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1,3-dimethyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide, with a yield of 43.75%.

[0043] Example 11: A method for preparing 7-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1,3,3-trimethyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide (i.e., compound B3), comprising the following steps: Steps (1)-(4): Refer to steps (1)-(4) of Example 10; Step (5): Referring to step (5) of Example 1, methyl-4-ethoxy-1-methyl-1H-benzo[c][1,2]thiazine-7-carboxylate-2,2-dioxide is replaced with methyl-1,3,3-trimethyl-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carboxylate-2,2-dioxide; Step (6): Referring to step (6) of Example 1, 4-ethoxy-1-methyl-1H-benzo[c][1,2]thiazine-7-carboxylic acid-2,2-dioxide is replaced with 1,3,3-trimethyl-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carboxylic acid-2,2-dioxide; Step (7): Preparation of 7-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1,3,3-trimethyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide (i.e., compound B3): Dissolve 1,3-dimethyl-1H-pyrazol-5-yl1,3-dimethyl-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carboxylate-2,2-dioxide (600.00 mg, 1.59 mmol) in 60 mL of acetonitrile, then add Et3N (241.31 mg, 2.38 mmol) and acetone cyanohydrin (13.53 mg, 0.16 mmol). After reacting at room temperature for 12-14 h, the extent of the reaction was monitored by TLC. After the reaction was complete, the solvent was evaporated under vacuum, the pH was adjusted with dilute hydrochloric acid solution, and the product was extracted with ethyl acetate, followed by washing with saturated NaCl. Finally, the crude product was subjected to column chromatography on silica gel using a dichloromethane / methanol gradient system to obtain 0.27 g of 7-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1,3,3-trimethyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide, with a yield of 45.00%.

[0044] Example 12: A method for preparing 3,3-diallyl-7-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1-methyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide (i.e., compound B4), comprising the following steps: Steps (1)-(3): Refer to steps (1)-(3) of Example 1; Step (4): Referring to step (4) of Example 1, bromoethane is replaced with 3-bromopropene; Step (5): Referring to step (5) of Example 1, methyl-4-ethoxy-1-methyl-1H-benzo[c][1,2]thiazine-7-carboxylate-2,2-dioxide is replaced with methyl-3,3-diallyl-1-methyl-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carboxylate-2,2-dioxide; Step (6): Referring to step (6) of Example 1, 3,3-diallyl-1-methyl-1H-benzo[c][1,2]thiazine-7-carboxylic acid-2,2-dioxide is replaced with 4-ethoxy-1-methyl-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carboxylic acid-2,2-dioxide; Step (7): Preparation of 3,3-diallyl-7-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1-methyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide (i.e., compound B4): Dissolve 1,3-dimethyl-1H-pyrazol-5-yl-3,3-diallyl-1-methyl-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carboxylate-2,2-dioxide (600.00 mg, 1.40 mmol) in 60 mL of acetonitrile, then add Et3N (212.05 mg, 2.10 mmol) and acetone cyanohydrin (11.89 mg, 0.14 mmol). After reacting at room temperature for 12-14 h, the extent of the reaction was monitored by TLC. After the reaction was completed, the solvent was evaporated under vacuum, the pH was adjusted with dilute hydrochloric acid solution, and the product was extracted with ethyl acetate and washed with saturated NaCl. Finally, the crude product was subjected to column chromatography on silica gel using a dichloromethane / methanol gradient system to obtain 0.18 g of 3,3-diallyl-7-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1-methyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide, with a yield of 30.00%.

[0045] Example 13: A method for preparing 7-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1-methyl-3-(methanesulfonyl)-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide (i.e., compound B5), comprising the following steps: Steps (1)-(3): Refer to steps (1)-(3) of Example 1; Step (4): Referring to step (4) of Example 1, bromoethane is replaced with methanesulfonic anhydride; Step (5): Referring to step (5) of Example 1, methyl-4-ethoxy-1-methyl-1H-benzo[c][1,2]thiazine-7-carboxylate-2,2-dioxide is replaced with methyl-1-methyl-3-(methanesulfonyl)-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carboxylate-2,2-dioxide; Step (6): Referring to step (6) of Example 1, 1-methyl-3-(methanesulfonyl)-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carboxylic acid-2,2-dioxide is replaced with 4-ethoxy-1-methyl-1H-benzo[c][1,2]thiazine-7-carboxylic acid-2,2-dioxide; Step (7): Preparation of 7-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1-methyl-3-(methanesulfonyl)-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide (i.e., compound B5): Dissolve 1,3-dimethyl-1H-pyrazol-5-yl-1-methyl-3-(methanesulfonyl)-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carboxylic acid ester-2,2-dioxide (700.00 mg, 1.64 mmol) in 70 mL of acetonitrile, then add Et3N (248.58 mg, 2.46 mmol) and acetone cyanohydrin (13.94 mg, 0.16 mmol). After reacting at room temperature for 12-14 h, the extent of the reaction was monitored by TLC. After the reaction was completed, the solvent was evaporated under vacuum, the pH was adjusted with dilute hydrochloric acid solution, and the product was extracted with ethyl acetate, followed by washing with saturated NaCl. Finally, the crude product was subjected to column chromatography on silica gel using a dichloromethane / methanol gradient system to obtain 0.14 g of 7-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1-methyl-3-(methanesulfonyl)-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide, with a yield of 20.00%.

[0046] Example 14: A method for preparing 7-(1,3-dimethyl-5-(2-(4-nitrophenyl)-2-oxoethoxy)-1H-pyrazole-4-carbonyl)-1-methyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide (i.e., compound B6), comprising the following steps: Steps (1)-(7): Refer to steps (1)-(7) of Example 9; Step (8): Preparation of 7-(1,3-dimethyl-5-(2-(4-nitrophenyl)-2-oxoethoxy)-1H-pyrazole-4-carbonyl)-1-methyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide (i.e., compound B6): Dissolve 7-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1-methyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide (400.00 mg, 1.14 mmol) in 40 mL of acetonitrile, then add potassium carbonate (237.36 mg, 1.72 mmol). After stirring at room temperature for half an hour, add 2-bromo-1-(4-nitrophenyl)ethane-1-one (335.30 mg, 1.37 mmol). The reaction system was heated to 85 °C and refluxed. After the reaction was complete, the system was concentrated under reduced pressure, extracted and purified by column chromatography to obtain 0.38 g of 7-(1,3-dimethyl-5-(2-(4-nitrophenyl)-2-oxoethoxy)-1H-pyrazole-4-carbonyl)-1-methyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide, with a yield of 75.35%.

[0047] Example 15: A method for preparing 4-(1,3-dimethyl-2,2-dioxo-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carbonyl)-1,3-dimethyl-1H-pyrazole-5-yl diethylcarbamate (i.e., compound B7), comprising the following steps: Steps (1)-(7): Refer to steps (1)-(7) of Example 10; Step (8): Preparation of 4-(1,3-dimethyl-2,2-dioxo-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carbonyl)-1,3-dimethyl-1H-pyrazole-5-yl diethylcarbamate (i.e., compound B7): Dissolve 7-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1,3-dimethyl-1H-benzo[c][1,2]thiazine-4(3H)-one 2,2-dioxide (500.00 mg, 1.38 mmol) in 40 mL of acetonitrile, then add potassium carbonate (285.24 mg, 2.06 mmol). Stir at room temperature for half an hour, then add diethylcarbamate chloride (223.88 mg, 1.65 mmol). The reaction system was heated to 85°C and refluxed. After the reaction was complete, the system was concentrated under reduced pressure, extracted and purified by column chromatography to obtain 0.32 g of 4-(1,3-dimethyl-2,2-dioxo-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carbonyl)-1,3-dimethyl-1H-pyrazole-5-yl diethylcarbamate, with a yield of 51.10%.

[0048] Example 16: A method for preparing 4-(1,3-dimethyl-2,2-dioxo-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carbonyl)-1,3-dimethyl-1H-pyrazole-5-yl-4-methylbenzenesulfonate (i.e., compound B8), comprising the following steps: Steps (1)-(7): Refer to steps (1)-(7) of Example 10; Step (8): Preparation of 4-(1,3-dimethyl-2,2-dioxo-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carbonyl)-1,3-dimethyl-1H-pyrazole-5-yl-4-methylbenzenesulfonate (i.e., compound B8): Dissolve 400.00 mg (1.10 mmol) of 7-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1,3-dimethyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide in 40 mL of acetonitrile, then add potassium carbonate (228.19 mg, 1.65 mmol). Stir at room temperature for half an hour, then add p-toluenesulfonyl chloride (251.82 mg). (mg, 1.32mmol), the reaction system was heated to 85℃ and refluxed. After the reaction was complete, the system was concentrated under reduced pressure, extracted and purified by column chromatography to obtain 0.37g of 4-(1,3-dimethyl-2,2-dioxo-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carbonyl)-1,3-dimethyl-1H-pyrazole-5-yl-4-methylbenzenesulfonate, with a yield of 64.85%.

[0049] Example 17: A method for preparing 1,3-dimethyl-4-(1,3,3-trimethyl-2,2-dioxo-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carbonyl)-1H-pyrazol-5-yl-4-methylbenzenesulfonate (i.e., compound B9), comprising the following steps: Steps (1)-(7): Refer to steps (1)-(7) of Example 11; Step (8): Preparation of 1,3-dimethyl-4-(1,3,3-trimethyl-2,2-dioxo-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carbonyl)-1H-pyrazol-5-yl-4-methylbenzenesulfonate (i.e., compound B9): Dissolve 400.00 mg (1.06 mmol) of 7-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1,3,3-trimethyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide in 40 mL of acetonitrile, then add potassium carbonate (219.71 mg, 1.59 mmol). Stir at room temperature for half an hour, then add p-toluenesulfonyl chloride (242.46 mg). (mg, 1.27mmol), the reaction system was heated to 85℃ and refluxed. After the reaction was complete, the system was concentrated under reduced pressure, extracted and purified by column chromatography to obtain 0.32g of 1,3-dimethyl-4-(1,3,3-trimethyl-2,2-dioxo-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carbonyl)-1H-pyrazole-5-yl-4-methylbenzenesulfonate, with a yield of 57.72%.

[0050] Example 18: A method for preparing 7-(1,3-dimethyl-5-(2-(4-nitrophenyl)-2-oxoethoxy)-1H-pyrazole-4-carbonyl)-1,3,3-trimethyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide (i.e., compound B10), comprising the following steps: Steps (1)-(7): Refer to steps (1)-(7) of Example 11; Step (8): Preparation of 7-(1,3-dimethyl-5-(2-(4-nitrophenyl)-2-oxoethoxy)-1H-pyrazole-4-carbonyl)-1,3,3-trimethyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide (i.e., compound B10): Dissolve 7-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1,3,3-trimethyl-1H-benzo[c][1,2]thiazin-4(3H)-one-2,2-dioxide (500.00 mg, 1.32 mmol) in 50 mL of acetonitrile, then add potassium carbonate (274.64 mg, 1.99 mmol). After stirring at room temperature for half an hour, add 2-bromo-1-(4-nitrophenyl)ethane-1-one (387.97 mg, 1.59 mmol). The reaction system was heated to 85 °C and refluxed. After the reaction was complete, the system was concentrated under reduced pressure, extracted and purified by column chromatography to obtain 0.48 g of 7-(1,3-dimethyl-5-(2-(4-nitrophenyl)-2-oxoethoxy)-1H-pyrazole-4-carbonyl)-1,3,3-trimethyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide, with a yield of 68.29%.

[0051] Example 19: A method for preparing 1-((1,3-dimethyl-4-(1,3,3-trimethyl-2,2-dioxo-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carbonyl)-1H-pyrazol-5-yl)oxy)ethyl ethyl carbonate (i.e., compound B11), comprising the following steps: Steps (1)-(7): Refer to steps (1)-(7) of Example 11; Step (8): Preparation of 1-((1,3-dimethyl-4-(1,3,3-trimethyl-2,2-dioxo-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carbonyl)-1H-pyrazol-5-yl)oxy)ethyl ethyl carbonate (i.e., compound B11): Dissolve 500.00 mg (1.32 mmol) of 7-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1,3,3-trimethyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide in 50 mL of acetonitrile, then add potassium carbonate (274.64 mg, 1.99 mmol). Stir at room temperature for half an hour, then add 1-chloroethyl ethyl carbonate (242.56 mg). (mg, 1.59mmol), the reaction system was heated to 85℃ and refluxed. After the reaction was complete, the system was concentrated under reduced pressure, extracted and purified by column chromatography to obtain 0.35g of 1-((1,3-dimethyl-4-(1,3,3-trimethyl-2,2-dioxo-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carbonyl)-1H-pyrazol-5-yl)oxy)ethyl carbonate, yield 54.97%.

[0052] Example 20: A method for preparing 7-(5-(2-(2-fluorophenyl)-2-oxoethoxy)-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1,3,3-trimethyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide (i.e., compound B12), comprising the following steps: Steps (1)-(7): Refer to steps (1)-(7) of Example 11; Step (8): Preparation of 7-(5-(2-(2-fluorophenyl)-2-oxoethoxy)-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1,3,3-trimethyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide (i.e., compound B12): Dissolve 7-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1,3,3-trimethyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide (500.00 mg, 1.32 mmol) in 50 mL of acetonitrile, then add potassium carbonate (274.64 mg, 1.99 mmol). After stirring at room temperature for half an hour, add 2-bromo-1-(2-fluorophenyl)ethane-1-one (345.04 mg, 1.59 mmol). The reaction system was heated to 85 °C and refluxed. After the reaction was complete, the system was concentrated under reduced pressure, extracted and purified by column chromatography to obtain 0.42 g of 7-(5-(2-(2-fluorophenyl)-2-oxoethoxy)-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1,3,3-trimethyl-1H-benzo[c][1,2]thiazine-4(3H)-one 2,2-dioxide, with a yield of 62.64%.

[0053] Example 21: A method for preparing 7-(5-(2-(2-fluorophenyl)-2-oxoethoxy)-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1,3,3-trimethyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide (i.e., compound B13), comprising the following steps: Steps (1)-(7): Refer to steps (1)-(7) of Example 11; Step (8): Preparation of 7-(5-(2-(2-fluorophenyl)-2-oxoethoxy)-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1,3,3-trimethyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide (i.e., compound B13): Dissolve 7-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1,3,3-trimethyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide (500.00 mg, 1.32 mmol) in 50 mL of acetonitrile, then add potassium carbonate (274.64 mg, 1.99 mmol). After stirring at room temperature for half an hour, add 2-bromo-1-(2,4-difluorophenyl)ethane-1-one (373.64 mg, 1.59 mmol). The reaction system was heated to 85 °C and refluxed. After the reaction was complete, the system was concentrated under reduced pressure, extracted and purified by column chromatography to obtain 0.45 g of 7-(5-(2-(2,4-difluorophenyl)-2-oxoethoxy)-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1,3,3-trimethyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide, with a yield of 64.77%.

[0054] Example 22: A method for preparing (1,3-dimethyl-4-(1,3,3-trimethyl-2,2-dioxo-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carbonyl)-1H-pyrazol-5-yl)oxy)methyl ethyl carbonate (i.e., compound B14), comprising the following steps: Steps (1)-(7): Refer to steps (1)-(7) of Example 11; Step (8): Preparation of (1,3-dimethyl-4-(1,3,3-trimethyl-2,2-dioxo-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carbonyl)-1H-pyrazol-5-yl)oxy)methyl ethyl carbonate (i.e., compound B14): Dissolve 500.00 mg (1.32 mmol) of 7-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1,3,3-trimethyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide in 50 mL of acetonitrile, then add potassium carbonate (274.64 mg, 1.99 mmol). Stir at room temperature for half an hour, then add chloromethyl ethyl carbonate (220.26 mg). (mg, 1.59mmol), the reaction system was heated to 85℃ and refluxed. After the reaction was complete, the system was concentrated under reduced pressure, extracted and purified by column chromatography to obtain 0.34 g of (1,3-dimethyl-4-(1,3,3-trimethyl-2,2-dioxo-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carbonyl)-1H-pyrazol-5-yl)oxy)methylethyl carbonate, yield 54.48%.

[0055] Example 23: A method for preparing 3-en-1-yl(1-((1,3-dimethyl-4-(1,3,3-trimethyl-2,2-dioxo-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carbonyl)-1H-pyrazol-5-yl)oxy)ethyl) carbonate (i.e., compound B15), comprising the following steps: Steps (1)-(7): Refer to steps (1)-(7) of Example 11; Step (8): Preparation of 3-en-1-yl(1-((1,3-dimethyl-4-(1,3,3-trimethyl-2,2-dioxo-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carbonyl)-1H-pyrazol-5-yl)oxy)ethyl) carbonate (i.e., compound B15): Dissolve 500.00 mg (1.32 mmol) of 7-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1,3,3-trimethyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide in 50 mL of acetonitrile, then add potassium carbonate (274.64 mg, 1.99 mmol). After stirring at room temperature for half an hour, add 3-butene-1-alkynyl carbonate (1-chloroethyl) ester (283.95 mg, 1.59 mmol). The reaction system was heated to 85°C and refluxed. After the reaction was complete, the system was concentrated under reduced pressure, extracted and purified by column chromatography to obtain 0.44 g of 3-en-1-yl(1-((1,3-dimethyl-4-(1,3,3-trimethyl-2,2-dioxo-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carbonyl)-1H-pyrazol-5-yl)oxy)ethyl) carbonate, with a yield of 63.95%.

[0056] Example 24: A method for preparing 7-(5-(2-(4-methoxyphenyl)-2-oxoethoxy)-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1,3,3-trimethyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide (i.e., compound B16), comprising the following steps: Steps (1)-(7): Refer to steps (1)-(7) of Example 11; Step (8): Preparation of 7-(5-(2-(4-methoxyphenyl)-2-oxoethoxy)-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1,3,3-trimethyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide (i.e., compound B16): Dissolve 7-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1,3,3-trimethyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide (500.00 mg, 1.32 mmol) in 50 mL of acetonitrile, then add potassium carbonate (274.64 mg, 1.99 mmol). After stirring at room temperature for half an hour, add 2-bromo-1-(4-methoxyphenyl)ethane-1-one (364.17 mg, 1.59 mmol). The reaction system was heated to 85℃ and refluxed. After the reaction was complete, the system was concentrated under reduced pressure, extracted and purified by column chromatography to obtain 0.35 g of 7-(5-(2-(4-methoxyphenyl)-2-oxoethoxy)-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1,3,3-trimethyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide, with a yield of 50.28%.

[0057] Example 25: A method for preparing 3,3-diallyl-7-(1,3-dimethyl-5-(2-(4-nitrophenyl)-2-oxoethoxy)-1H-pyrazole-4-carbonyl)-1-methyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide (i.e., compound B17), comprising the following steps: Steps (1)-(7): Refer to steps (1)-(7) of Example 12; Step (8): Preparation of 3,3-diallyl-7-(1,3-dimethyl-5-(2-(4-nitrophenyl)-2-oxoethoxy)-1H-pyrazole-4-carbonyl)-1-methyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide (i.e., compound B17): Dissolve 3,3-diallyl-7-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1-methyl-1H-benzo[c][1,2]thiazin-4(3H)-one-2,2-dioxide (500.00 mg, 1.16 mmol) in 50 mL of acetonitrile, then add potassium carbonate (241.34 mg, 1.75 mmol). After stirring at room temperature for half an hour, add 2-bromo-1-(4-nitrophenyl)ethane-1-one (340.93 mg, 1.40 mmol). The reaction system was heated to 85 °C and refluxed. After the reaction was complete, the system was concentrated under reduced pressure, extracted and purified by column chromatography to obtain 0.42 g of 3,3-diallyl-7-(1,3-dimethyl-5-(2-(4-nitrophenyl)-2-oxoethoxy)-1H-pyrazole-4-carbonyl)-1-methyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide, with a yield of 60.95%.

[0058] Example 26: A method for preparing 1-((4-(3,3-diallyl-1-methyl-2,2-dioxo-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carbonyl)-1,3-dimethyl-1H-pyrazol-5-yl)oxy)ethyl ethyl carbonate (i.e., compound B18), comprising the following steps: Steps (1)-(7): Refer to steps (1)-(7) of Example 12; Step (8): Preparation of 1-((4-(3,3-diallyl-1-methyl-2,2-dioxo-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carbonyl)-1,3-dimethyl-1H-pyrazol-5-yl)oxy)ethyl ethyl carbonate (i.e., compound B18): Dissolve 3,3-diallyl-7-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1-methyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide (500.00 mg, 1.16 mmol) in 50 mL of acetonitrile, then add potassium carbonate (241.34 mg, 1.75 mmol). Stir at room temperature for half an hour, then add 1-chloroethyl ethyl carbonate (213.15 mg, 1.40 mmol). The reaction system was heated to 85°C and refluxed. After the reaction was complete, the system was concentrated under reduced pressure, extracted and purified by column chromatography to obtain 0.43 g of 1-((4-(3,3-diallyl-1-methyl-2,2-dioxo-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carbonyl)-1,3-dimethyl-1H-pyrazol-5-yl)oxy)ethyl carbonate, with a yield of 67.71%.

[0059] The structural and molecular formulas of the target compounds obtained in the above examples are shown in Table 1, and their physicochemical properties and spectral information are shown in Table 2. Table 1. Molecular formulas and structural formulas of the target compounds obtained in Examples 1-26

[0060] Table 2. Spectral data of the target compounds obtained in Examples 1-26

[0061] Pre-seeding activity assay of target compounds: This experiment employed the petri dish method, using various weeds as test subjects. Seeds were sterilized with 75% ethanol before the experiment and germinated rapidly until they showed signs of sprouting in a constant-temperature incubator. Germinated seeds were placed in 12-well plates with two layers of filter paper, 4-6 seeds per well. 1 mL of the target compound solution at concentrations of 100 µg / mL and 10 µg / mL was added to each well, with water as a blank control and trifluralin and benzoyl permethrin as positive controls. After treatment, the petri dishes were placed in an artificial climate incubator at 75% relative humidity, with automatic cycling between 16 h of light (28 °C) and 8 h of darkness (25 °C). After 5 days of incubation, the stem and root lengths of the weed seeds were measured with a ruler, and the inhibition rate was calculated. Each experiment had three parallel groups, and each experiment was repeated three times.

[0062] Table 3. Pre-emergence herbicidal activity of the target compounds in Examples 1-26 at 100 and 10 µg / mL.

[0063] Post-seeding activity test of target compound: This experiment used a spray method, with various weeds as test subjects. Weed seeds were evenly scattered in 8 x 8 cm plastic pots filled two-thirds with organic substrate and grown in a greenhouse. The pots were used for testing when both grasses and broadleaf weeds reached the two- to three-leaf stage. 100... μ The compound was dissolved in L DMF and diluted with 0.1% Tween-80 to a dose of 300 g ai / ha. Benzoflubenzuron and mesotrione were used as positive controls and target compounds, respectively, to spray all weeds. After treatment, the weeds were left in a greenhouse for 21 days, and their herbicidal activity was evaluated visually in the control (CK) group, repeated three times.

[0064] Table 4. Post-emergence herbicidal activity of the target compounds in Examples 1-26

[0065] Crop safety evaluation of the target compound: This experiment used a spray method, with various weeds as test subjects. Weed seeds were evenly scattered in 8 x 8 cm plastic pots filled two-thirds with organic substrate and grown in a greenhouse. The pots were used for testing when both grasses and broadleaf weeds reached the two- to three-leaf stage. 100... μ The compound was dissolved in L DMF and diluted with 0.1% Tween-80 to a dose of 150 g ai / ha. Trifluralin and benzoate were used as positive controls and target compounds, respectively, to spray all weeds. After treatment, the weeds were placed in a greenhouse for 30 days, and their herbicidal activity was evaluated visually in the control group (CK), repeated three times.

[0066] Table 5. Crop safety of the target compounds in Examples 12, 18, and 26 at a dose of 150 g ai / ha.

[0067] As can be seen from Table 3, at 100 μ At a concentration of g / mL, compounds A3, A7, B7, and B18 showed inhibitory effects of over 80% on the roots of purslane, while compounds A3, A6, B9, B13, and B18 showed inhibitory effects of over 80% on the stems. Compounds A3 and B18 also showed inhibitory effects of over 80% on both the roots and stems of purslane. Furthermore, compounds A7, B4, B11, B12, and B13 showed inhibitory effects at a concentration of 100 g / mL. μ At a concentration of g / mL, its inhibitory effect on barnyardgrass roots exceeded 80%, showing superior activity compared to benzoxazine and mesotrione.

[0068] As shown in Table 4, at a dosage of 300 g ai / ha, most compounds exhibited excellent herbicidal activity against Abutilon theophrasti, Amaranthus retroflexus, and Portulaca oleracea, causing the weeds to wither and their growth to be severely inhibited, with inhibition rates reaching 100%. Among them, compounds B4, B10, and B16 not only showed 100% herbicidal activity against Amaranthus retroflexus, Portulaca oleracea, and Abutilon theophrasti, but also exhibited herbicidal activity exceeding 80% against monocotyledonous weeds such as Barnyardgrass, Setaria viridis, and Eleusine indica. In particular, compound B10 showed a 100% inhibition rate against all six weeds.

[0069] As shown in Table 5, compounds B4, B10, and B16 exhibited superior crop safety compared to benzoxazine and mesotrione in crops such as rice, corn, wheat, peanut, soybean, and cotton. Among them, compounds B4 and B10 showed crop safety of no more than 10% in broadleaf crops such as corn, peanut, and cotton.

[0070] In summary, this series of benzothiazide pyrazole derivatives exhibits excellent herbicidal and inhibitory activity. Therefore, this series of compounds can be used as novel pre-emergence and post-emergence herbicides, and further development of novel selective herbicides will enable their application in more farmland.

[0071] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Any simple modifications, equivalent changes, and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope of the present invention.

Claims

1. A benzothiazinone pyrazole derivative, characterized in that, The general structural formula of the derivative is as shown in formula (I): In formula (I): R 1 Selected from H, C1-C6 alkyl, C1-C6 haloalkyl, and C1-C6 alkoxy; R 2 R 3 R 4 They are selected from H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy; C3-C6 alkenyl, C3-C6 alkynyl; respectively. R 5 H, C1-C6 alkylsulfonyl, C1-C6 haloalkyl, C1-C6 alkoxy, (C1-C4)alkoxy-(C1-C6)alkylsulfonyl or phenylsulfonyl, benzoyl, (C1-C4)alkylbenzoyl-(C1-C6)alkyl or benzyl, -CONR 6 R 7 -SO2-Ar-R 8 -C-CO-Ar-R 9 R 10 , 1-methylethyl ethyl carbonate, (ethoxycarbonyloxy)methyl, but-3-enyl (1-chloroethyl) carbonate-methane; R 6 R 7 R 8 Each is independently selected from C1-C6 alkyl groups; R 9 R 10 They are selected from hydrogen, nitro, halogen, and C1-C4 alkyl groups, respectively.

2. The benzothiazide pyrazole derivative as described in claim 1, characterized in that, Including the following compounds: Compound A1: (4-ethoxy-1-methyl-2,2-dioxo-1H-benzo[c][1,2]thiazin-7-yl)(5-hydroxy-1,3-dimethyl-1H-pyrazol-4-yl) methyl ketone; Compound A2: (5-hydroxy-1,3-dimethyl-1H-pyrazol-4-yl)(1-methyl-2,2-dioxo-4-propoxy-1H-benzo[c][1,2]thiazin-7-yl) methyl ketone; Compound A3: (5-hydroxy-1,3-dimethyl-1H-pyrazol-4-yl)(1-methyl-2,2-dioxo-4-propoxy-3-propyl-1H-benzo[c][1,2]thiazin-7-yl) methyl ketone; Compound A4: (4-ethoxy-3-ethyl-1-methyl-2,2-dioxo-1H-benzo[c][1,2]thiazin-7-yl)(5-hydroxy-1,3-dimethyl-1H-pyrazol-4-yl) methyl ketone; Compound A5: 4-(4-ethoxy-1-methyl-2,2-dioxo-1H-benzo[c][1,2]thiazine-7-carbonyl)-1,3-dimethyl-1H-pyrazol-5-yl-4-methylbenzenesulfonate; Compound A6: 2-((4-(4-ethoxy-1-methyl-2,2-dioxo-1H-benzo[c][1,2]thiazine-7-carbonyl)-1,3-dimethyl-1H-pyrazol-5-yl)oxy)-1-(4-nitrophenyl)ethane-1-one; Compound A7: 2-((1,3-dimethyl-4-(1-methyl-2,2-dioxo-4-propoxy-1H-benzo[c][1,2]thiazine-7-carbonyl)-1H-pyrazol-5-yl)oxy)-1-(4-nitrophenyl)ethane-1-one; Compound A8: 2-((1,3-dimethyl-4-(1-methyl-2,2-dioxo-4-propoxy-3-propyl-1H-benzo[c][1,2]thiazine-7-carbonyl)-1H-pyrazol-5-yl)oxy)-1-(4-nitrophenyl)ethane-1-one; Compound B1: 7-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1-methyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide; Compound B2: 7-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1,3-dimethyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide; Compound B3: 7-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1,3,3-trimethyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide; Compound B4: 3,3-diallyl-7-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1-methyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide; Compound B5: 7-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1-methyl-3-(methanesulfonyl)-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide; Compound B6: 7-(1,3-dimethyl-5-(2-(4-nitrophenyl)-2-oxoethoxy)-1H-pyrazole-4-carbonyl)-1-methyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide; Compound B7: 4-(1,3-dimethyl-2,2-dioxo-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carbonyl)-1,3-dimethyl-1H-pyrazole-5-yldiethylcarbamate; Compound B8: 4-(1,3-dimethyl-2,2-dioxo-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carbonyl)-1,3-dimethyl-1H-pyrazole-5-yl 4-methylbenzenesulfonate; Compound B9: 1,3-dimethyl-4-(1,3,3-trimethyl-2,2-dioxo-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carbonyl)-1H-pyrazol-5-yl 4-methylbenzenesulfonate; Compound B10: 7-(1,3-dimethyl-5-(2-(4-nitrophenyl)-2-oxoethoxy)-1H-pyrazole-4-carbonyl)-1,3,3-trimethyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide; Compound B11: 1-((1,3-dimethyl-4-(1,3,3-trimethyl-2,2-dioxo-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carbonyl)-1H-pyrazol-5-yl)oxy)ethyl carbonate; Compound B12: 7-(5-(2-(2-fluorophenyl)-2-oxoethoxy)-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1,3,3-trimethyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide; Compound B13: 7-(5-(2-(2,4-difluorophenyl)-2-oxoethoxy)-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1,3,3-trimethyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide; Compound B14: (1,3-dimethyl-4-(1,3,3-trimethyl-2,2-dioxo-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carbonyl)-1H-pyrazol-5-yl)oxy)methyl ethyl carbonate; Compound B15: 3-en-1-yl(1-((1,3-dimethyl-4-(1,3,3-trimethyl-2,2-dioxo-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carbonyl)-1H-pyrazol-5-yl)oxy)ethyl) carbonate; Compound B16: 7-(5-(2-(4-methoxyphenyl)-2-oxoethoxy)-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1,3,3-trimethyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide; Compound B17: 3,3-diallyl-7-(1,3-dimethyl-5-(2-(4-nitrophenyl)-2-oxoethoxy)-1H-pyrazole-4-carbonyl)-1-methyl-1H-benzo[c][1,2]thiazine-4(3H)-one-2,2-dioxide; Compound B18: 1-((4-(3,3-diallyl-1-methyl-2,2-dioxo-4-oxo-3,4-dihydro-1H-benzo[c][1,2]thiazine-7-carbonyl)-1,3-dimethyl-1H-pyrazol-5-yl)oxy)ethyl carbonate.

3. The method for preparing benzothiazinone pyrazole derivatives according to any one of claims 1-2, characterized in that, Includes the following steps: (1) Preparation of intermediate 1: Dimethyl aminoterephthalate and triethylamine were added to dichloromethane (DCM), and the mixture was reacted at room temperature for 30 minutes. Then, methanesulfonic anhydride was added and the reaction was carried out at room temperature. After the reaction was completed, the mixture was extracted with water and ethyl acetate, concentrated under reduced pressure, dried and subjected to column chromatography to obtain intermediate 1. (2) Preparation of intermediate 2: Intermediate 1 was dissolved in DMF solution, cesium carbonate was added at room temperature and stirred for 30 minutes; then iodomethane was added and the reaction was stirred continuously at room temperature for 5 hours; after the reaction was complete, dilute hydrochloric acid solution was added and the pH of the mixture was adjusted to about 7. Then, it was extracted with water and ethyl acetate, concentrated under reduced pressure, dried and subjected to column chromatography to obtain intermediate 2. (3) Preparation of intermediate 3: Intermediate 2 was dissolved in DMF solution, and NaH was added under ice bath conditions and stirred continuously until the mixture was homogeneous. The mixture was reacted at room temperature for 3 hours. After the reaction was completed, dilute hydrochloric acid solution was added and the pH of the mixture was adjusted to about 7. The mixture was then extracted with a large amount of water and ethyl acetate, concentrated under reduced pressure, dried and subjected to column chromatography to obtain intermediate 3. (4) Preparation of intermediate 4a-4h: Intermediate 3 was stirred and mixed at room temperature for 30 minutes under the conditions of Cs2CO3 and DMF as catalyst and solvent, and then a haloalkane or methanesulfonic anhydride was added and the temperature was raised to 80℃ for 7-8 h. After the reaction was completed, dilute hydrochloric acid solution was added to adjust the pH, and then the mixture was extracted, concentrated under reduced pressure and dried. Intermediate 4a-4h was obtained by column chromatography eluting with petroleum ether and ethyl acetate. (5) Preparation of intermediates 5a-5i: Intermediate 4a-4h, lithium hydroxide, and 80% methanol solution were mixed and stirred. The mixture was stirred continuously at room temperature for 6 hours. After the reaction was complete, the reaction solution was poured into ice water. Then, dilute hydrochloric acid solution was added while stirring. When the pH of the mixture was adjusted to 2-3, a solid precipitated out. The solid was obtained by filtration and dried in vacuum to obtain intermediate 5a-5i. (6) Preparation of intermediates 6a-6i: Dissolve 5a-5i in dry dichloromethane, then add triethylamine and 2-chloro-1-methylpyridine iodide (CMPI), and stir continuously until homogeneous. Then add 1,3-dimethyl-5-pyrazolone and triethylamine at room temperature, allowing the reaction system to react for 10-12 hours at room temperature. After the reaction is complete, wash with saturated sodium bicarbonate solution, dry with anhydrous sodium sulfate, and recrystallize to obtain 1,3-dimethyl-1 H -Pyrazole-5-dimethyl-substituted benzothiazide ketone carbamate, namely intermediate 6a-6i; (7) Preparation of benzothiazinone pyrazole derivatives of the target compound: Intermediate 6a-6i was dissolved in acetonitrile, and then triethylamine and acetone cyanohydrin were added. The reaction was carried out at room temperature for 12-14 h, and the extent of the reaction was monitored by TLC. After the reaction was completed, the solvent was evaporated under vacuum, the pH was adjusted with dilute hydrochloric acid solution, and the product was extracted with ethyl acetate and washed with saturated NaCl. Finally, the crude product was subjected to column chromatography on silica gel using a dichloromethane / methanol gradient system to obtain benzoylpyrazole derivatives. (8) Preparation of the target compound containing benzothiazinone pyrazole derivatives: A portion of the target compound obtained above was mixed with potassium carbonate in acetonitrile solution. Various substituted halides were added at room temperature, and the reaction system was heated to 85°C for reflux reaction. After the reaction was complete, the system was concentrated under reduced pressure, extracted and purified by column chromatography to obtain another portion of pyrazole derivatives containing thiamethoxamone.

4. The method for preparing the benzothiazinone pyrazole derivative as described in claim 3, characterized in that, In step (1), the molar ratio of dimethyl terephthalate, triethylamine, and methanesulfonic anhydride is: dimethyl terephthalate: triethylamine: methanesulfonic anhydride = 1:1.5:1.2; the amount of DCM is controlled by adding 1 mL of DCM per millimol of dimethyl terephthalate; in step (2), the molar ratio of intermediate 1, cesium carbonate, and iodomethane is: intermediate 1: cesium carbonate: iodomethane = 1:1.5:1.2; the amount of DMF is controlled by adding 1 mL of DMF per millimol of intermediate 1; in step (3), the molar ratio of intermediate 2 and NaH is: intermediate 2: NaH = 1:1.5; the amount of DMF is controlled by adding 1 mL of DMF per millimol of intermediate 2. The dosage is controlled by mL; in step (4), the dosage of intermediate 3, cesium carbonate and haloalkanes is in the molar ratio of: intermediate 3: cesium carbonate: haloalkanes = 1:1.5:1.5; the dosage of DMF is controlled by adding 1 mL of dichloromethane per millimol of intermediate 3; in step (5), the dosage of intermediate 4a-4h and lithium hydroxide is in the molar ratio of: intermediate 4a-4h: lithium hydroxide = 1:2; the dosage of 80% methanol is controlled by adding 1 mL of 80% methanol per millimol of intermediate 4a-4h; In step (6), the amounts of intermediate 5a-5i, 1,3-dimethyl-5-pyrazolone, triethylamine, and CMPI are calculated in the following molar ratio: intermediate 5a-5i: 1,3-dimethyl-5-pyrazolone: ​​triethylamine: CMPI = 1:1.25:2:1.25; the amount of dichloromethane is controlled by adding 1 mL of dichloromethane per millimol of intermediate 5a-5i.

5. The method for preparing the benzothiazinone pyrazole derivative as described in claim 3, characterized in that, In step (7), the amounts of intermediate 6a-6i, triethylamine, and acetone cyanohydrin are calculated in the following molar ratio: intermediate 6a-6i: triethylamine: acetone cyanohydrin = 1:1.5:0.1; the amount of acetonitrile is controlled by adding 1 mL of acetonitrile per millimol of intermediate 6a-6i. In step (8), the amounts of the target compound, potassium carbonate, and halogenated hydrocarbons are calculated in the following molar ratio: target compound: potassium carbonate: multiple substituted halides = 1:1.5:1.2; the amount of acetonitrile is controlled by adding 1 mL of acetonitrile per millimol of the target compound.

6. The use of the benzothiazide pyrazole derivative as described in claim 1 in the preparation of herbicides or weed growth enzyme inhibitors.

7. The application as described in claim 6, characterized in that, The weeds mentioned are goosegrass, barnyard grass, velvetleaf, amaranth, purslane, and foxtail grass.

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