1,3-dithiane-substituted pyrazole derivatives, processes for their preparation and use

Abstract

The application belongs to the field of organic chemistry and provides a 1,3-dithiane-substituted pyrazole derivative as well as a preparation method and application thereof. 1 The alkyl or aryl group, and the aryl group. 2 The application provides a method using a cheap base as a promoter, avoids using a noble metal catalyst, has mild reaction conditions, simple operation, wide substrate applicability, high regioselectivity, efficiently functionalizes the C-3 position which is usually not reactive for a pyrazole framework, and has strong practicability and industrial application prospects. The method provided by the application can be used for synthesis and later modification of natural products, drug molecules and functional material molecules.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of organic synthetic chemistry, and specifically relates to a 1,3-dithiane-substituted pyrazole derivative and a preparation method and application thereof. BACKGROUND

[0002] Pyrazole derivatives have various pharmacological properties, including antithrombotic, anticancer and analgesic effects (Nature. 2024, 630(8016), 429-436. J. Med. Chem. 2024, 67(11), 8988-9027. Bioorg Chem. 2020, 97.), and are the core structure of several drugs approved by the US Food and Drug Administration (FDA) (such as Celebrex, Lonazolac, Acomplia, etc.) (Chem. Rev. 2021, 121(3), 1670-1715.). The [3+2] cycloaddition reaction of sydnone with alkyne has become one of the most effective methods for constructing pyrazole rings.

[0003] Therefore, the synthesis of pyrazole compounds from sydnone and alkyne shows important application value in many fields such as medicine, biology, materials, etc. However, so far, the synthesis of such skeletons mainly has the following shortcomings, including harsh reaction conditions, poor regioselectivity and limited substrate range (Chem. Commun. 2017, 53(84), 11515-11527. Beilstein J. Org. Chem. 2018, 14, 1317-1348. Chem. Rev. 2021, 121(12), 6718-6743.). Therefore, it is very valuable to develop a method for synthesizing regioselective pyrazole compounds with non-noble metal catalysis, mild conditions and simple operation.

[0004] 1,3-dithiane, as an aldehyde ketone protecting group and a polarity conversion reagent, can couple acyl carbon with electrophiles and form carbon-carbon (C-C) bonds, and plays an important role in organic synthesis and total synthesis of natural products (J. Am. Chem. Soc. 2019, 141, 8088-8092. Sci. Adv. 2024, 10, eadp9375. J. Am. Chem. Soc. 2023, 145, 18240-18246.). 1,3-dithiane-substituted drug molecules can consume ROS (reactive oxygen species) in vivo, reduce oxidative stress (ACS Nano. 2022, 16, 21225-21239). At the same time, the introduced sulfur atom can change the liposolubility, metabolic stability and bioavailability of the drug molecule, thereby optimizing the pharmacokinetic properties of the drug. SUMMARY

[0005] The application aims to provide a 1,3-dithiane-substituted pyrazole derivative, a preparation method and application thereof, namely, 2-ethynyl-1,3-dithiane derivative, sydney ketone compound, suitable solvent and base are sequentially added in a reactor, and reaction is carried out at room temperature to obtain a pyrazole compound.

[0006] The application relates to a 1,3-dithiane-substituted pyrazole derivative, a preparation method and application thereof.

[0007]

[0008] R in structure (I) is an aliphatic substituent (the substituent is selected from hydrogen, methyl, ethyl and the like), a substituted phenyl (the substituent is selected from one or more of hydrogen, methoxy, fluorine, chlorine, trifluoromethoxy), a naphthyl group, a benzofuranyl group, a thiophenyl group and the like; R 1 is a substituted phenyl (the substituent is selected from one or more of hydrogen, methoxy, fluorine, chlorine, bromine, trifluoromethoxy), a benzodioxolyl group. 2

[0009] The application relates to a preparation method of a 1,3-dithiane-substituted pyrazole derivative.

[0010]

[0011] In the technical solution, the organic solvent is one of dimethyl sulfoxide (DMSO) and N,N-dimethylformamide (DMF).

[0012] The base is one of potassium tert-butoxide, sodium tert-butoxide and sodium methoxide.

[0013] In the technical solution, the molar ratio of the base, 2-ethynyl-1,3-dithiane derivative (II) and sydney ketone compound (III) is 2:1:1.

[0014] ​The reaction steps include: adding 2-ethynyl-1,3-dithiane derivative, sylvanone compound, suitable solvent and base into the reaction bottle in sequence, stirring the reaction at room temperature for 15 minutes, monitoring the reaction by thin layer chromatography, adding saturated brine into the reaction system slowly to quench the reaction after the raw material is completely consumed, extracting with ethyl acetate (15 ml) for three times, washing the combined organic phase with saturated brine (40 ml) for three times, drying with anhydrous sodium sulfate, filtering, removing volatile matter under vacuum, and obtaining the product by column chromatography. DETAILED DESCRIPTION

[0015] The following examples can make the professional technical personnel more fully understand the present application, but do not limit the present application in any way. The raw materials used in the present application are known compounds, which can be purchased on the market or synthesized by known methods in the art.

[0016] Example 1: Preparation of compound 3-(1,3-dithiane-2-yl)-1,4-diphenyl-1H-pyrazole:

[0017] In a dry dimethyl sulfoxide (2 ml) solution, 2-(phenylethynyl)-1,3-dithiane (22 mg, 0.1 mmol), phenyl sylvanone (16.3 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) were added in sequence. The resulting mixture was stirred vigorously at room temperature for 15 minutes. The mixture was quenched with water (5 ml) and extracted with ethyl acetate (10 ml x 3). The combined organic layer was washed with saturated brine (10 ml x 3) and dried with anhydrous sodium sulfate, filtered, and the filtrate was concentrated in vacuum. The product was obtained by column chromatography with a yield of 72%.

[0018] The structure and nuclear magnetic resonance data of the product obtained in Example 1, 3-(1,3-dithiane-2-yl)-1,4-diphenyl-1H-pyrazole, are as follows:

[0019]

[0020] 3-(1,3-dithiane-2-yl)-1,4-diphenyl-1H-pyrazole 1 H NMR (400 MHz, CDCl3) δ 7.92 (s, 1H), 7.79-7.72 (m, 2H), 7.59-7.53 (m, 2H), 7.48-7.41 (m, 4H), 7.39-7.33 (m, 1H), 7.31-7.27 (m, 1H), 5.31 (s, 1H), 3.13-3.06 (m, 2H), 3.04-2.96 (m, 2H), 2.22-2.08 (m, 2H). 13C NMR (101 MHz, CDC13) δ 149.4, 139.9, 132.2, 129.4, 129.0, 128.6, 127.4, 126.7, 125.4, 122.7, 119.4, 42.4, 31.5, 25.5.

[0021] Example 2: Preparation of compound 3-(l,3-dithian-2-yl)-l-(4-fluorophenyl)-4- phenyl-lH-pyrazole:

[0022] To a solution of dry dimethylsulfoxide (2 mL) was added 2-(phenylethynyl)-l,3- dithiane (22 mg, 0.1 mmol), the corresponding sylvanone (18 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) successively. The resulting mixture was stirred vigorously at room temperature for 15 min. The mixture was quenched with water (5 mL) and extracted with ethyl acetate (10 mL x 3). The combined organic layers were washed with saturated brine (10 mL x 3) and dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated in vacuo. The product was obtained in 70% yield by column chromatography.

[0023] The structure and NMR data of the product obtained in Example 2, 3-(l,3-dithian-2-yl)-l- (4-fluorophenyl)-4-phenyl-lH-pyrazole, are as follows:

[0024]

[0025] 3-(l,3-dithian-2-yl)-l-(4-fluorophenyl)-4-phenyl-lH-pyrazole 1 H NMR (400 MHz, CDC13) δ 7.86 (s, 1H), 7.74 - 7.69 (m, 2H), 7.58 - 7.53 (m, 2H), 7.49 - 7.43 (m, 2H), 7.39 - 7.34 (m, 1H), 7.17 - 7.10 (m, 2H), 5.31 (s, 1H), 3.09 - 2.98 (m, 4H), 2.20 - 2.09 (m, 2H). 13 C NMR (101 MHz, CDC13) δ 161.38 (d, J = 247.4 Hz), 149.4, 136.2, 132.1, 129.0, 128.6, 127.4, 125.5, 122.8, 121.2 (d, J = 8.3 Hz), 116.2 (d, J = 22.9 Hz), 42.5, 31.7, 25.5. 19 F NMR (377 MHz, CDC13) δ -115.7.

[0026] Preparation of the product 3-(1,3-dithian-2-yl)-1 -(4-chlorophenyl)-4-phenyl- 1 H-pyrazole obtained in Example 3:

[0027] To a solution of dry dimethylsulfoxide (2 mL) was added 2-(phenylethynyl)-1,3-dithiane (22 mg, 0.1 mmol), the corresponding sylvanone (19.6 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) successively. The resulting mixture was stirred vigorously at room temperature for 15 min. The mixture was quenched with water (5 mL) and extracted with ethyl acetate (10 mL x 3). The combined organic layers were washed with saturated brine (10 mL x 3) and dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated in vacuo. The product was obtained in 75% yield by column chromatography.

[0028] The structure and NMR data of the product 3-(1,3-dithian-2-yl)-1 -(4-chlorophenyl)-4- phenyl-1 H-pyrazole obtained in Example 3 are as follows:

[0029]

[0030] 3-(1,3-dithian-2-yl)-1 -(4-chlorophenyl)-4-phenyl-1 H-pyrazole 1 H NMR (400 MHz, CDCI3) δ 7.88 (s, 1 H), 7.70 (d, J = 8.9 Hz, 2H), 7.57 - 7.52 (m, 2H), 7.49 - 7.43 (m, 2H), 7.43 - 7.39 (m, 1 H), 5.29 (s, 1 H), 3.11 - 2.96 (m, 4H), 2.21 - 2.06 (m, 2H). 13 C NMR (101 MHz, CDCI3) δ 149.7, 138.4, 132.2, 131.9, 129.5, 129.0, 128.6, 127.5, 125.3, 123.1, 120.5, 42.5, 31.6, 25.5.

[0031] Preparation of the product 3-(1,3-dithian-2-yl)-1 -(4-chlorophenyl)-4-phenyl- 1 H-pyrazole obtained in Example 3:

[0032] To a solution of 2-(phenylethynyl)-1,3-dithiane (22 mg, 0.1 mmol) in dry dimethylsulfoxide (2 mL) was added the corresponding sydnone compound (23.9 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) successively. The resulting mixture was stirred vigorously at room temperature for 15 min. The mixture was quenched with water (5 mL) and extracted with ethyl acetate (10 mL x 3). The combined organic layers were washed with saturated brine (10 mL x 3) and dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated in vacuo. The product was obtained in 73% yield by column chromatography.

[0033] The structure and NMR data of the product obtained in Example 4, 3-(1,3-dithian-2-yl)-1-(4-bromophenyl)-4-phenyl-1H-pyrazole, are as follows:

[0034]

[0035] 3-(1,3-dithian-2-yl)-1-(4-bromophenyl)-4-phenyl-1H-pyrazole 1 H NMR (400 MHz, CDC13) δ 7.88 (s, 1H), 7.64 (d, J = 8.8 Hz, 2H), 7.58 - 7.55 (m, 2H), 7.53 (d, J = 2.5 Hz, 2H), 7.45 (t, J = 7.6 Hz, 2H), 7.39 - 7.33 (m, 1H), 5.29 (s, 1H), 3.11 - 2.95 (m, 4H), 2.21 - 2.08 (m, 2H). 13 C NMR (101 MHz, CDC13) δ 149.7, 138.8, 132.5, 131.9, 129.0, 128.6, 127.5, 125.2, 123.1, 120.7, 120.0, 42.4, 31.6, 25.4.

[0036] Preparation of the product obtained in Example 5, 4-(3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazol-1-yl)benzonitrile:

[0037] To a solution of 2-(phenylethynyl)-1,3-dithiane (22 mg, 0.1 mmol) in dry dimethylsulfoxide (2 mL) was added the corresponding sydnone compound (18.7 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) successively. The resulting mixture was stirred vigorously at room temperature for 15 min. The mixture was quenched with water (5 mL) and extracted with ethyl acetate (10 mL x 3). The combined organic layers were washed with saturated brine (10 mL x 3) and dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated in vacuo. The product was obtained in 75% yield by column chromatography.

[0038] The structure and NMR data of the product 4-(3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazol-1-yl)benzonitrile obtained in Example 5 are as follows:

[0039]

[0040] 4-(3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazol-1-yl)benzonitrile 1 H NMR (400MHz, CDCl3) δ7.98(s,1H),7.89(d,J=8.8Hz,2H),7.74(d,J=8.8Hz,2H),7.58–7.51(m, 2H),7.51–7.43(m,2H),7.43–7.34(m,1H),5.28(s,1H),3.14–2.95(m,4H),2.25–2.04(m,2H). 13 C NMR (101MHz, CDCl3) δ151.0,142.6,133.7,131.4,129.1,128.6,127.9,125.3,124.1,119.1,118.5,109.9,42.2,31.5,25.4.

[0041] Preparation of the product obtained in Example 6: 3-(1,3-dithian-2-yl)-4-phenyl-1-(4-(trifluoromethoxy)phenyl)-1H-pyrazole:

[0042] 2-(Phenylacetyl)-1,3-dithiane (22 mg, 0.1 mmol), the corresponding Sydney ketone compound (24.6 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) were added sequentially to a solution of dry dimethyl sulfoxide (2 ml). The resulting mixture was vigorously stirred at room temperature for 15 minutes. The mixture was quenched with water (5 ml) and extracted with ethyl acetate (10 ml × 3). The combined organic layers were washed with saturated brine (10 ml × 3), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated in vacuo. The product was obtained by column chromatography with a yield of 67%.

[0043] The structure and NMR data of the product obtained in Example 6, 3-(1,3-dithian-2-yl)-4-phenyl-1-(4-(trifluoromethoxy)phenyl)-1H-pyrazole, are as follows:

[0044]

[0045] 3-(1,3-Dithian-2-yl)-4-phenyl-1-(4-(trifluoromethoxy)phenyl)-1H-pyrazole 1H NMR (400 MHz, CDC13) δ 7.89 (s, 1H), 7.81 - 7.74 (m, 2H), 7.58 - 7.52 (m, 2H), 7.49 - 7.42 (m, 2H), 7.39 - 7.34 (m, 1H), 7.29 (d, J = 8.7 Hz, 2H), 5.29 (s, 1H), 3.11 - 2.95 (m, 4H), 2.21 - 2.07 (m, 2H). 13 C NMR (101 MHz, CDC13) δ 149.9, 147.5, 138.3, 131.9, 129.0, 128.6, 127.6, 125.4, 123.2, 122.1, 120.6 (q, J = 257.2 Hz), 120.5, 42.4, 31.6, 25.5. 19 F NMR (377 MHz, CDC13) δ -58.0.

[0046] Preparation of the product 3-(1,3-dithian-2-yl)-4-phenyl-1-(4-(trifluoromethyl)phenyl)-1H- pyrazole from Example 7:

[0047] To a solution of dimethyl sulfoxide (2 mL) was added 2-(phenylethynyl)-1,3-dithiane (22 mg, 0.1 mmol), the corresponding sylvanone (23 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) sequentially. The resulting mixture was stirred vigorously at room temperature for 15 min. The mixture was quenched with water (5 mL) and extracted with ethyl acetate (10 mL x 3). The combined organic layers were washed with saturated brine (10 mL x 3) and dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated in vacuo. The product was obtained by column chromatography in 69% yield.

[0048] The structure and NMR data of the product 3-(1,3-dithian-2-yl)-4-phenyl-1-(4-(trifluoromethyl)phenyl)-1H-pyrazole from Example 7 are as follows:

[0049]

[0050] 3-(1,3-dithian-2-yl)-4-phenyl-1-(4-(trifluoromethyl)phenyl)-1H-pyrazole 1 H NMR (400 MHz, CDC13) δ 7.97 (s, 1H), 7.88 (d, J = 8.5 Hz, 2H), 7.69 (d, J = 8.5 Hz, 2H), 7.59 - 7.51 (m, 2H), 7.51 - 7.42 (m, 2H), 7.42 - 7.33 (m, 1H), 5.29 (s, 1H), 3.13 - 2.96 (m, 4H), 2.23 - 2.06 (m, 2H).13 CNMR (101 MHz, CDC13) δ 150.4, 142.1, 131.7, 128.9, 128.6, 128.5 (q, J = 32.8 Hz) 127.7, 126.8 (q, J = 3.7 Hz), 125.3, 124.1 (q, J = 271.9 Hz), 123.6, 118.9, 42.3, 31.5, 25.4. 19 F NMR (377 MHz, CDC13) δ -62.2.

[0051] Preparation of the product 3-(1,3-dithian-2-yl)-4-phenyl-1-(4-(methyloxy)phenyl)-1H- pyrazole from Example 8:

[0052] To a solution of dry dimethylsulfoxide (2 mL) was added 2-(phenylethynyl)-1,3-dithiane (22 mg, 0.1 mmol), the corresponding sylvanone (19.2 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) sequentially. The resulting mixture was stirred vigorously at room temperature for 15 min. The mixture was quenched with water (5 mL) and extracted with ethyl acetate (10 mL x 3). The combined organic layers were washed with saturated brine (10 mL x 3) and dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated in vacuo and the product was obtained by column chromatography in 65% yield.

[0053] The structure and NMR data of the product 3-(1,3-dithian-2-yl)-4-phenyl-1-(4- (methyloxy)phenyl)-1H-pyrazole from Example 8 are as follows:

[0054]

[0055] 3-(1,3-dithian-2-yl)-4-phenyl-1-(4-(methyloxy)phenyl)-1H-pyrazole 1 H NMR (400 MHz, CDC13) δ 7.82 (s, 1H), 7.65 (d, J = 9.0 Hz, 2H), 7.59 - 7.51 (m, 2H), 7.49 - 7.41 (m, 2H), 7.39 - 7.31 (m, 1H), 7.00 - 6.91 (m, 2H), 5.31 (s, 1H), 3.84 (s, 3H), 3.12 - 2.94 (m, 4H), 2.22 - 2.07 (m, 2H). 13 C NMR (101 MHz, CDC13) δ 158.5, 148.8, 133.7, 132.4, 129.0, 128.6, 127.3, 125.4, 122.3, 121.1, 114.5, 55.7, 42.6, 31.7, 25.5.

[0056] Preparation of the product 1-(3,5-dichlorophenyl)-3-(1,3-dithian-2-yl)-4- phenyl-1H-pyrazole from Example 9:

[0057] To a solution of dimethylsulfoxide (2 mL) was added 2-(phenylethynyl)-1,3- dithiane (22 mg, 0.1 mmol), the corresponding sylvanone (23 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) successively. The resulting mixture was stirred vigorously at room temperature for 15 min. The mixture was quenched with water (5 mL) and extracted with ethyl acetate (10 mL x 3). The combined organic layers were washed with saturated brine (10 mL x 3) and dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated in vacuo. The product was obtained in 72% yield by column chromatography.

[0058] The structure and NMR data of the product 1-(3,5-dichlorophenyl)-3-(1,3-dithian-2- yl)-4-phenyl-1H-pyrazole from Example 9 are as follows:

[0059]

[0060] 1-(3,5-dichlorophenyl)-3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazole 1 H NMR (400 MHz, CDC13) δ 7.88 (s, 1H), 7.70 - 7.67 (m, 2H), 7.56 - 7.51 (m, 2H), 7.48 - 7.42 (m, 2H), 7.40 - 7.34 (m, 1H), 5.28 (s, 1H), 3.08 - 2.98 (m, 4H), 2.21 - 2.09 (m, 2H). 13 CNMR (101 MHz, CDC13) δ 150.4, 141.1, 135.9, 131.5, 129.1, 128.6, 127.7, 126.5, 125.3, 123.7, 117.6, 42.4, 31.6, 25.4.

[0061] Preparation of the product 1-(3,5-dichlorophenyl)-3-(1,3-dithian-2-yl)-4- phenyl-1H-pyrazole from Example 9:

[0062] To a solution of 2-(phenylethynyl)-1,3-dithiane (22 mg, 0.1 mmol) in dry dimethylsulfoxide (2 mL) was added the corresponding sylvanone compound (19.6 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) successively. The resulting mixture was stirred vigorously at room temperature for 15 min. The mixture was quenched with water (5 mL) and extracted with ethyl acetate (10 mL x 3). The combined organic layers were washed with saturated brine (10 mL x 3) and dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated in vacuo. The product was obtained in 71% yield by column chromatography.

[0063] The structure and NMR data of the product obtained in Example 10, 1-(3- chlorophenyl)-3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazole, are as follows:

[0064]

[0065] 1-(3- chlorophenyl)-3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazole 1 H NMR (400 MHz, CDC13) δ 7.90 (s, 1H), 7.82 (t, J = 2.1 Hz, 1H), 7.64 - 7.59 (m, 1H), 7.57 - 7.52 (m, 2H), 7.49 - 7.42 (m, 2H), 7.40 - 7.33 (m, 2H), 7.27 - 7.23 (m, 1H), 5.29 (s, 1H), 3.11 - 2.96 (m, 4H), 2.22 - 2.06 (m, 2H). 13 C NMR (101 MHz, CDC13) δ 149.9, 140.7, 135.3, 131.8, 130.4, 129.0, 128.6, 127.6, 126.7, 125.3, 123.2, 119.6, 117.1, 42.4, 31.6, 25.5.

[0066] Preparation of the product obtained in Example 11, 1-(3-bromophenyl)-3-(1,3- dithian-2-yl)-4-phenyl-1H-pyrazole:

[0067] To a solution of 2-(phenylethynyl)-1,3-dithiane (22 mg, 0.1 mmol) in dry dimethylsulfoxide (2 mL) was added the corresponding sylvanone compound (19.6 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) successively. The resulting mixture was stirred vigorously at room temperature for 15 min. The mixture was quenched with water (5 mL) and extracted with ethyl acetate (10 mL x 3). The combined organic layers were washed with saturated brine (10 mL x 3) and dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated in vacuo. The product was obtained in 71% yield by column chromatography.

[0068] The structure and NMR data of the product obtained in Example 11, 1-(3-bromophenyl)-3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazole, are as follows:

[0069]

[0070] 1-(3-bromophenyl)-3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazole 1 H NMR (400 MHz, CDC13) δ 8.00 - 7.95 (m, 1H), 7.90 (s, 1H), 7.70 - 7.63 (m, 1H), 7.57 - 7.52 (m, 2H), 7.49 - 7.43 (m, 2H), 7.42 - 7.34 (m, 2H), 7.33 - 7.27 (m, 1H), 5.29 (s, 1H), 3.12 - 2.94 (m, 4H), 2.24 - 2.04 (m, 2H). 13 CNMR (101 MHz, CDC13) δ 149.9, 140.8, 131.8, 130.7, 129.7, 129.0, 128.6, 127.6, 125.4, 123.2, 123.2, 122.4, 117.6, 42.5, 31.6, 25.5.

[0071] Preparation of the product obtained in Example 12, 1-(3-methoxyphenyl)-3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazole:

[0072] To a solution of dry dimethyl sulfoxide (2 mL) was added 2-(phenylethynyl)-1,3-dithiane (22 mg, 0.1 mmol), the corresponding sylvanone compound (19.2 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) successively. The resulting mixture was stirred vigorously at room temperature for 15 min. The mixture was quenched with water (5 mL) and extracted with ethyl acetate (10 mL x 3). The combined organic layers were washed with saturated brine (10 mL x 3) and dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated in vacuo. The product was obtained by column chromatography in 68% yield.

[0073] The structure and NMR data of the product obtained in Example 12, 1-(3-methoxyphenyl)-3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazole, are as follows:

[0074]

[0075] 1-(3-methoxyphenyl)-3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazole. 1H NMR (400 MHz, CDC13) δ 7.90 (s, 1H), 7.58 - 7.54 (m, 2H), 7.45 (t, J = 7.6 Hz, 2H), 7.37 - 7.28 (m, 4H), 6.85 - 6.81 (m, 1H), 5.30 (s, 1H), 3.88 (s, 3H), 3.14 - 3.07 (m, 2H), 3.03 - 2.96 (m, 2H), 2.19 - 2.11 (m, 2H). 13 C NMR (101 MHz, CDC13) δ 160.6, 149.4, 141.1, 132.2, 130.2, 129.0, 128.6, 127.4, 125.6, 122.7, 112.5, 111.6, 105.6, 55.7, 42.4, 31.5, 25.5.

[0076] Preparation of the product from Example 13, 1-(4-bromo-3-chlorophenyl)-3-(1,3- dithian-2-yl)-4-phenyl-1H-pyrazole:

[0077] To a solution of dimethyl sulfoxide (2 mL) was added 2-(phenylethynyl)-1,3-dithiane (22 mg, 0.1 mmol), the corresponding sylvanone (27.3 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) successively. The resulting mixture was stirred vigorously at room temperature for 15 min. The mixture was quenched with water (5 mL) and extracted with ethyl acetate (10 mL x 3). The combined organic layers were washed with saturated brine (10 mL x 3) and dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated in vacuo. The product was obtained by column chromatography in 70% yield.

[0078] The structure and NMR data of the product from Example 13, 1-(4-bromo-3-chlorophenyl)-3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazole, are as follows:

[0079]

[0080] 1-(4-bromo-3-chlorophenyl)-3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazole 1 H NMR (400 MHz, CDC13) δ 7.94 - 7.91 (m, 1H), 7.88 (s, 1H), 7.68 - 7.62 (m, 1H), 7.56 - 7.52 (m, 2H), 7.52 - 7.48 (m, 1H), 7.48 - 7.42 (m, 2H), 7.39 - 7.34 (m, 1H), 5.28 (s, 1H), 3.12 - 2.94 (m, 4H), 2.24 - 2.03 (m, 2H). 13C NMR (101 MHz, CDC13) δ 150.2, 139.6, 135.6, 134.3, 131.6, 129.0, 128.6, 127.7, 125.2, 123.6, 120.9, 119.9, 118.2, 42.4, 31.6, 25.4.

[0081] Preparation of the product 1 -(4-chlorophenyl)-3-(1,3-dithian-2-yl)-1 H-pyrazole from Example 14:

[0082] To a solution of dry dimethylsulfoxide (2 mL) was added 2-ethynyl-1,3-dithiane (14.4 mg, 0.1 mmol), the corresponding sylvanone (19.6 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) sequentially. The resulting mixture was stirred vigorously at room temperature for 15 min. The mixture was quenched with water (5 mL) and extracted with ethyl acetate (10 mL x 3). The combined organic layers were washed with saturated brine (10 mL x 3) and dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated in vacuo. The product was obtained in 68% yield by column chromatography.

[0083] The structure and NMR data of the product 1 -(4-chlorophenyl)-3-(1,3-dithian-2-yl)-1 H-pyrazole from Example 14 are as follows:

[0084]

[0085] 1 -(4-chlorophenyl)-3-(1,3-dithian-2-yl)-1 H-pyrazole 1 H NMR (600 MHz, CDC13) δ 7.83 (d, J = 2.5 Hz, 1 H), 7.58 - 7.54 (m, 4H), 6.57 (d, J = 2.5 Hz, 1 H), 5.41 (s, 1 H), 3.08 - 3.04 (m, 2H), 3.00 - 2.96 (m, 2H), 2.20 - 2.17 (m, 1 H), 2.03 - 1.99 (m, 1 H). 13 C NMR (151 MHz, CDC13) δ 152.4, 139.1, 132.5, 127.8, 120.8, 119.9, 107.0, 44.3, 31.4, 25.4.

[0086] Preparation of the product 1 -(4-chlorophenyl)-3-(1,3-dithian-2-yl)-1 H-pyrazole from Example 14:

[0087] To a solution of 2-ethynyl-1,3-dithiane (14.4 mg, 0.1 mmol) in dry dimethylsulfoxide (2 mL) was added the corresponding sylvanone compound (23.9 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) successively. The resulting mixture was stirred vigorously at room temperature for 15 min. The mixture was quenched with water (5 mL) and extracted with ethyl acetate (10 mL x 3). The combined organic layers were washed with saturated brine (10 mL x 3) and dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated in vacuo. The product was obtained in 70% yield by column chromatography.

[0088] The structure and NMR data of the product obtained in Example 15, 1-(4- bromophenyl)-3-(1,3-dithian-2-yl)-1H-pyrazole, are as follows:

[0089]

[0090] 1-(4-bromophenyl)-3-(1,3-dithian-2-yl)-1H-pyrazole 1 H NMR (600 MHz, CDC13) δ 7.82 (d, J = 2.4 Hz, 1H), 7.64 - 7.61 (m, 2H), 7.41 - 7.38 (m, 2H), 6.57 (d, J = 2.5 Hz, 1H), 5.42 (s, 1H), 3.08 - 3.03 (m, 2H), 3.00 - 2.95 (m, 2H), 2.21 - 2.16 (m, 1H), 2.04 - 1.98 (m, 1H). 13 C NMR (151 MHz, CDC13) δ 152.4, 138.6, 132.2, 129.6, 127.9, 120.5, 106.9, 44.3, 31.4, 25.4.

[0091] Preparation of the product obtained in Example 16, 1-(benzo[d][1,3]dioxol-5-yl)-3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazole:

[0092] To a solution of 2-(phenylethynyl)-1,3-dithiane (22 mg, 0.1 mmol) in dry dimethylsulfoxide (2 mL) was added the corresponding sylvanone compound (20.6 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) successively. The resulting mixture was stirred vigorously at room temperature for 15 min. The mixture was quenched with water (5 mL) and extracted with ethyl acetate (10 mL x 3). The combined organic layers were washed with saturated brine (10 mL x 3) and dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated in vacuo. The product was obtained in 57% yield by column chromatography.

[0093] The structure and NMR data of the product obtained in Example 16, 1-(benzo[d][1,3]dioxol-5-yl)-3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazole, are as follows:

[0094]

[0095] 1-(benzo[d][1,3]dioxol-5-yl)-3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazole 1 HNMR (400 MHz, CDC13) δ 7.80 (s, 1H), 7.58 - 7.50 (m, 2H), 7.45 (t, J = 7.6 Hz, 2H), 7.39 - 7.28 (m, 2H), 7.15 (dd, J = 8.4, 2.2 Hz, 1H), 6.83 (d, J = 8.3 Hz, 1H), 6.02 (s, 2H), 5.29 (s, 1H), 3.13 - 3.04 (m, 2H), 3.04 - 2.94 (m, 2H), 2.20 - 2.08 (m, 2H). 13 CNMR (101 MHz, CDC13) δ 149.0, 148.5, 146.5, 134.9, 132.2, 129.0, 128.6, 127.3, 125.6, 122.4, 112.7, 108.3, 102.1, 101.9, 42.5, 31.6, 25.5.

[0096] Preparation of the product obtained in Example 17, 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazole:

[0097] To a solution of dimethyl sulfoxide (2 mL) was added 2-(phenylethynyl)-1,3-dithiane (22 mg, 0.1 mmol), the corresponding sylvanone (24.2 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) successively. The resulting mixture was stirred vigorously at room temperature for 15 min. The mixture was quenched with water (5 mL) and extracted with ethyl acetate (10 mL x 3). The combined organic layers were washed with saturated brine (10 mL x 3) and dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated in vacuo. The product was obtained by column chromatography in 62% yield.

[0098] The structure and NMR data of the product obtained in Example 17, 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazole, are as follows:

[0099]

[0100] 1 -(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-3-(1,3-dithian-2-yl)-4-phenyl-1 H- pyrazole 1 H NMR (400 MHz, CDC13) δ 7.84 (s, 1H), 7.58 (d, J = 2.2 Hz, 1H), 7.57 - 7.50 (m, 2H), 7.49 - 7.43 (m, 2H), 7.43 - 7.33 (m, 2H), 7.10 (d, J = 8.7 Hz, 1H), 5.29 (s, 1H), 3.12 - 2.94 (m, 4H), 2.24 - 2.02 (m, 2H). 13 C NMR (101 MHz, CDC13) δ 149.8, 144.4, 142.3, 136.3, 131.8, 131.6 (t, J = 254.8 Hz), 129.0, 128.6, 127.6, 125.5, 123.2, 114.2, 109.7, 102.6, 77.5, 77.2, 76.8, 42.4, 31.6, 25.5. 19 F NMR (377 MHz, CDC13) δ -49.8

[0101] Preparation of the product 1 -(4-bromobiphenyl)-3-(1,3-dithian-2-yl)-4-(6- methoxynaphthalen-2-yl)-1 H-pyrazole from Example 18:

[0102] To a solution of dimethyl sulfoxide (2 mL) was added 2-((6-methoxynaphthalen-2- yl)ethynyl)-1,3-dithiane (30 mg, 0.1 mmol), the corresponding sylvanone compound (23.9 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) sequentially. The resulting mixture was stirred vigorously at room temperature for 15 min. The mixture was quenched with water (5 mL) and extracted with ethyl acetate (10 mL x 3). The combined organic layers were washed with saturated brine (10 mL x 3) and dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated in vacuo. The product was obtained by column chromatography in 71 % yield.

[0103] The structure and NMR data of the product 1 -(4-bromobiphenyl)-3-(1,3-dithian-2-yl)-4-(6- methoxynaphthalen-2-yl)-1 H-pyrazole from Example 18 are as follows:

[0104]

[0105] 1 -(4-bromobiphenyl)-3-(1,3-dithian-2-yl)-4-(6-methoxynaphthalen-2-yl)-1 H-pyrazole 1HNMR (400 MHz, CDC13) δ 7.93 (m, 2H), 7.80-7.75 (m, 2H), 7.65-7.58 (m, 3H), 7.55-7.52 (m, 2H), 7.20-7.15 (m, 2H), 5.35 (s, 1H), 3.93 (s, 3H), 3.10-3.04 (m, 2H), 3.02-2.95 (m, 2H), 2.19-2.08 (m, 2H). 13 C NMR (101 MHz, CDC13) δ 158.0, 149.9, 138.8, 133.8, 132.4, 129.6, 129.1, 127.4, 127.3, 127.1, 127.0, 125.3, 123.2, 120.7, 119.9, 119.4, 105.8, 55.5, 42.6, 31.6, 25.5.

[0106] Preparation of the product 3-(l,3-dithian-2-yl)-4-(4-fluorophenyl)-l-phenyl-lH- pyrazole from Example 19:

[0107] To a solution of dimethyl sulfoxide (2 mL) was added 2-((4-fluorophenyl)ethynyl)- 1,3-dithiane (23.8 mg, 0.1 mmol), phenyl sydnone compound (16.3 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) sequentially. The resulting mixture was stirred vigorously at room temperature for 15 min. The mixture was quenched with water (5 mL) and extracted with ethyl acetate (10 mL x 3). The combined organic layers were washed with saturated brine (10 mL x 3) and dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated in vacuo. The product was obtained by column chromatography in 71% yield.

[0108] The structure and NMR data of the product 3-(l,3-dithian-2-yl)-4-(4-fluorophenyl)-l- phenyl-lH-pyrazole from Example 19 are as follows:

[0109]

[0110] 3-(l,3-dithian-2-yl)-4-(4-fluorophenyl)-l-phenyl-lH-pyrazole 1 HNMR (400 MHz, CDC13) δ 7.89 (s, 1H), 7.77-7.72 (m, 2H), 7.56-7.48 (m, 2H), 7.48-7.39 (m, 2H), 7.32-7.27 (m, 1H), 7.18-7.10 (m, 2H), 5.25 (s, 1H), 3.12-3.05 (m, 2H), 3.04-2.95 (m, 2H), 2.22-2.05 (m, 2H).13 C NMR (101 MHz, CDC13) δ 162.3 (d, J = 246.7 Hz), 149.3, 139.8, 130.3 (d, J = 8.0 Hz), 129.5, 128.2 (d, J = 3.4 Hz), 126.8, 125.4, 121.8, 119.4, 115.9 (d, J = 21.4 Hz), 42.5, 31.6, 25.5. 19 F NMR (377 MHz, CDC13) δ -114.9.

[0111] Preparation of the product 3-(l,3-dithian-2-yl)-4-(4-chlorophenyl)-l-phenyl-lH- pyrazole from Example 20:

[0112] To a solution of dimethyl sulfoxide (2 mL) was added 2-((4-chlorophenyl)ethynyl)- 1,3-dithiane (25.3 mg, 0.1 mmol), phenyl sydnone compound (16.3 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) sequentially. The resulting mixture was stirred vigorously at room temperature for 15 min. The mixture was quenched with water (5 mL) and extracted with ethyl acetate (10 mL x 3). The combined organic layers were washed with saturated brine (10 mL x 3) and dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated in vacuo. The product was obtained by column chromatography in 73% yield.

[0113] The structure and NMR data of the product 3-(l,3-dithian-2-yl)-4-(4-chlorophenyl)-l- phenyl-lH-pyrazole from Example 20 are as follows:

[0114]

[0115] 3-(l,3-dithian-2-yl)-4-(4-chlorophenyl)-l-phenyl-lH-pyrazole 1 H NMR (400 MHz, CDC13) δ 7.91 (s, 1H), 7.78 - 7.71 (m, 2H), 7.53 - 7.48 (m, 2H), 7.47 - 7.40 (m, 4H), 7.34 - 7.27 (m, 1H), 5.25 (s, 1H), 3.12 - 3.05 (m, 2H), 3.04 - 2.96 (m, 2H), 2.22 - 2.06 (m, 2H). 13 C NMR (101 MHz, CDC13) δ 149.2, 139.7, 133.4, 130.7, 129.9, 129.5, 129.2, 126.9, 125.5, 121.6, 119.4, 42.6, 31.6, 25.5.

[0116] Preparation of the product 3-(l,3-dithian-2-yl)-4-(4-trifluoromethoxyphenyl)-l- phenyl-lH-pyrazole from Example 21:

[0117] To a solution of dry dimethylsulfoxide (2 mL) was added 2-((4- trifluoromethoxyphenyl)ethynyl)-l,3-dithiane (30.4 mg, 0.1 mmol), phenyl sydnone (16.3 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) sequentially. The resulting mixture was stirred vigorously at room temperature for 15 min. The mixture was quenched with water (5 mL) and extracted with ethyl acetate (10 mL x 3). The combined organic layers were washed with saturated brine (10 mL x 3) and dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated in vacuo. The product was obtained in 69% yield by column chromatography.

[0118] The structure and NMR data of the product 3-(l,3-dithian-2-yl)-4-(4- trifluoromethoxyphenyl)-l-phenyl-lH-pyrazole from Example 21 are as follows:

[0119]

[0120] 3-(l,3-dithian-2-yl)-4-(4-trifluoromethoxyphenyl)-l-phenyl-lH-pyrazole 1 H NMR (400 MHz, CDC13) δ 7.92 (s, 1H), 7.78 - 7.72 (m, 2H), 7.63 - 7.56 (m, 2H), 7.48 - 7.41 (m, 2H), 7.33 - 7.27 (m, 3H), 5.26 (s, 1H), 3.13 - 3.06 (m, 2H), 3.05 - 2.97 (m, 2H), 2.25 - 2.04 (m, 2H). 13 C NMR (101 MHz, CDC13) δ 149.2, 148.6, 139.7, 131.0, 130.0, 129.5, 127.0, 125.6, 121.5, 121.4, 120.66 (d, J = 257.1 Hz), 119.4, 42.5, 31.6, 25.4. 19 F NMR (377 MHz, CDC13) δ -57.8.

[0121] Preparation of the product 3-(l,3-dithian-2-yl)-4-(4-methoxyphenyl)-l-phenyl-lH- pyrazole from Example 22:

[0122] To a solution of dimethylsulfoxide (2 mL) was added 2-((4-methoxyphenyl)ethynyl)-1,3-dithiane (25 mg, 0.1 mmol), phenyl sydnone compound (16.3 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) successively. The resulting mixture was stirred vigorously at room temperature for 15 min. The mixture was quenched with water (5 mL) and extracted with ethyl acetate (10 mL x 3). The combined organic layer was washed with saturated brine (10 mL x 3) and dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated in vacuo. The product was obtained by column chromatography in 64% yield.

[0123] The structure and NMR data of the product obtained in Example 22, 3-(1,3-dithian-2-yl)-4-(4-methoxyphenyl)-1-phenyl-1H-pyrazole, are as follows:

[0124]

[0125] 3-(1,3-dithian-2-yl)-4-(4-methoxyphenyl)-1-phenyl-1H-pyrazole 1 H NMR (400 MHz, CDC13) δ 7.87 (s, 1H), 7.77 - 7.71 (m, 2H), 7.51 - 7.46 (m, 2H), 7.46 - 7.40 (m, 2H), 7.31 - 7.26 (m, 1H), 7.02 - 6.96 (m, 2H), 5.28 (s, 1H), 3.86 (s, 3H), 3.13 - 3.05 (m, 2H), 3.04 - 2.95 (m, 2H), 2.21 - 2.09 (m, 2H). 13 C NMR (101 MHz, CDC13) δ 159.0, 149.3, 139.9, 129.8, 129.4, 126.6, 125.0, 124.5, 122.3, 119.3, 114.4, 55.4, 42.5, 31.5, 25.5.

[0126] Preparation of the product obtained in Example 23, 3-(1,3-dithian-2-yl)-4-(3-methoxyphenyl)-1-phenyl-1H-pyrazole:

[0127] To a solution of dimethylsulfoxide (2 mL) was added 2-((3-methoxyphenyl)ethynyl)-1,3-dithiane (25 mg, 0.1 mmol), phenyl sydnone compound (16.3 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) successively. The resulting mixture was stirred vigorously at room temperature for 15 min. The mixture was quenched with water (5 mL) and extracted with ethyl acetate (10 mL x 3). The combined organic layer was washed with saturated brine (10 mL x 3) and dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated in vacuo. The product was obtained by column chromatography in 64% yield.

[0128] The structure and NMR data of the product obtained in Example 23, 3-(1,3-dithian-2-yl)-4-(3-methoxyphenyl)-1-phenyl-1H-pyrazole, are as follows:

[0129]

[0130] 3-(1,3-dithian-2-yl)-4-(3-methoxyphenyl)-1-phenyl-1H-pyrazole 1 H NMR (400 MHz, CDC13) δ 7.93 (s, 1H), 7.79 - 7.72 (m, 2H), 7.47 - 7.41 (m, 2H), 7.39 - 7.33 (m, 1H), 7.31 - 7.27 (m, 1H), 7.20 - 7.16 (m, 1H), 7.15 - 7.11 (m, 1H), 6.93 - 6.88 (m, 1H), 5.33 (s, 1H), 3.86 (s, 3H), 3.13 - 3.06 (m, 2H), 3.05 - 2.96 (m, 2H), 2.22 - 2.09 (m, 2H). 13 C NMR (101 MHz, CDC13) δ 160.0, 149.3, 139.8, 133.5, 130.0, 129.4, 126.8, 125.4, 122.6, 120.9, 119.4, 113.9, 113.2, 55.4, 42.6, 31.6, 25.5.

[0131] Preparation of the product obtained in Example 24, 4-(4-(benzyloxy)-3-methoxyphenyl)-3-(1,3-dithian-2-yl)-1-phenyl-1H-pyrazole:

[0132] To a solution of dimethylsulfoxide (2 mL) was added 2-((4-(benzyloxy)-3- methoxyphenyl)ethynyl)-1,3-dithiane (35.6 mg, 0.1 mmol), phenyl sydnone compound (16.3 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) successively. The resulting mixture was stirred vigorously at room temperature for 15 min. The mixture was quenched with water (5 mL) and extracted with ethyl acetate (10 mL x 3). The combined organic layer was washed with saturated brine (10 mL x 3) and dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated in vacuo. The product was obtained in 70% yield by column chromatography.

[0133] The structure and NMR data of the product obtained in Example 24, 4-(4-(benzyloxy)-3- methoxyphenyl)-3-(1,3-dithian-2-yl)-1-phenyl-1H-pyrazole, are as follows:

[0134]

[0135] 4-(4-(benzyloxy)-3-methoxyphenyl)-3-(1,3-dithian-2-yl)-1-phenyl-1H-pyrazole 1 H NMR (400 MHz, CDC13) δ 7.87 (s, 1H), 7.77 - 7.71 (m, 2H), 7.47 (d, J = 7.0 Hz, 2H), 7.40 (dd, J = 16.2, 7.8 Hz, 4H), 7.34 - 7.29 (m, 1H), 7.28 - 7.22 (m, 2H), 7.02 - 6.92 (m, 2H), 5.29 (s, 1H), 5.20 (s, 2H), 3.94 (s, 3H), 3.13 - 3.04 (m, 2H), 3.03 - 2.94 (m, 2H), 2.19 - 2.08 (m, 2H). 13 C NMR (101 MHz, CDC13) δ 149.9, 149.3, 147.6, 139.9, 137.2, 129.4, 128.7, 128.0, 127.4, 126.6, 125.4, 125.0, 122.6, 120.8, 119.3, 114.4, 112.6, 71.2, 56.2, 42.7, 31.6, 25.5.

[0136] Preparation of the product obtained in Example 25, 3-(1,3-dithian-2-yl)-1-phenyl-4-(2,4,5- trimethoxyphenyl)-1H-pyrazole:

[0137] To a solution of dimethylsulfoxide (2 mL) was added 2-((2,4,5- trimethoxyphenyl)ethynyl)-1,3-dithiane (31 mg, 0.1 mmol), phenyl Sydney ketone compound (16.3 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) successively. The resulting mixture was stirred vigorously at room temperature for 15 min. The mixture was quenched with water (5 mL) and extracted with ethyl acetate (10 mL x 3). The combined organic layer was washed with saturated brine (10 mL x 3) and dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated in vacuo. The product was obtained in 72% yield by column chromatography.

[0138] The structure and NMR data of the product obtained in Example 25, 3-(1,3- dithian-2-yl)-1-phenyl-4-(2,4,5-trimethoxyphenyl)-1H-pyrazole, are as follows:

[0139]

[0140] 3-(1,3- dithian-2-yl)-1-phenyl-4-(2,4,5-trimethoxyphenyl)-1H-pyrazole 1 H NMR (400 MHz, CDC13) δ 8.00 (s, 1H), 7.78 - 7.73 (m, 2H), 7.47 - 7.40 (m, 2H), 7.29 - 7.24 (m, 1H), 7.22 (s, 1H), 6.64 (s, 1H), 5.21 (s, 1H), 3.95 (s, 3H), 3.89 (s, 3H), 3.80 (s, 3H), 3.20 - 3.10 (m, 2H), 2.99 - 2.88 (m, 2H), 2.19 - 2.09 (m, 2H). 13 C NMR (101 MHz, CDC13) δ 151.1, 150.4, 149.0, 143.3, 140.0, 129.3, 126.9, 126.5, 119.3, 117.4, 114.5, 112.4, 98.3, 56.7, 56.6, 56.3, 42.6, 31.3, 25.6.

[0141] Preparation of the product obtained in Example 26, 4-(benzofuran-5-yl)-3-(1,3- dithian-2-yl)-1-phenyl-1H-pyrazole:

[0142] To a solution of dimethylsulfoxide (2 mL) was added 5-((1,3-dithia-2-yl)ethynyl)benzofuran (26 mg, 0.1 mmol), phenyl sydnone compound (16.3 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) successively. The resulting mixture was stirred vigorously at room temperature for 15 min. The mixture was quenched with water (5 mL) and extracted with ethyl acetate (10 mL x 3). The combined organic layer was washed with saturated brine (10 mL x 3) and dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated in vacuo. The product was obtained by column chromatography in 61% yield.

[0143] The structure and NMR data of the product obtained in Example 26, 4-(benzofuran-5-yl)-3-(1,3-dithian-2-yl)-1-phenyl-1H-pyrazole, are as follows:

[0144]

[0145] 4-(benzofuran-5-yl)-3-(1,3-dithian-2-yl)-1-phenyl-1H-pyrazole 1 H NMR (400 MHz, CDC13) δ 7.93 (s, 1H), 7.80 - 7.74 (m, 3H), 7.68 (d, J = 2.2 Hz, 1H), 7.58 (d, J = 8.5 Hz, 1H), 7.50 - 7.41 (m, 3H), 7.32 - 7.27 (m, 1H), 6.83 (dd, J = 2.2, 0.9 Hz, 1H), 5.32 (s, 1H), 3.13 - 3.05 (m, 2H), 3.04 - 2.94 (m, 2H), 2.20 - 2.10 (m, 2H). 13 C NMR (101 MHz, CDC13) δ 154.5, 149.5, 145.8, 139.9, 129.4, 128.1, 126.9, 126.7, 125.5, 125.3, 122.9, 121.3, 119.3, 111.8, 106.9, 77.5, 77.2, 76.8, 42.3, 31.5, 25.5.

[0146] Preparation of the product obtained in Example 27, 3-(1,3-dithian-2-yl)-1-phenyl-4-(thiophen-2-yl)-1H-pyrazole:

[0147] To a solution of dimethylsulfoxide (2 mL) was added 2-(thiophen-2-ylethynyl)-1,3-dithiane (22.5 mg, 0.1 mmol), phenyl Sydney ketone compound (16.3 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) successively. The resulting mixture was stirred vigorously at room temperature for 15 min. The mixture was quenched with water (5 mL) and extracted with ethyl acetate (10 mL x 3). The combined organic layer was washed with saturated brine (10 mL x 3) and dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated in vacuo. The product was obtained by column chromatography in 70% yield.

[0148] The structure and NMR data of the product obtained in Example 27, 3-(1,3-dithian-2-yl)-1-phenyl-4-(thiophen-2-yl)-1H-pyrazole, are as follows:

[0149]

[0150] 3-(1,3-dithian-2-yl)-1-phenyl-4-(thiophen-2-yl)-1H-pyrazole 1 H NMR (400 MHz, CDC13) δ 7.98 (s, 1H), 7.74 (dd, J = 7.7, 1.6 Hz, 2H), 7.44 (t, J = 7.9 Hz, 2H), 7.33 - 7.26 (m, 3H), 7.12 (dd, J = 5.1, 3.5 Hz, 1H), 5.42 (s, 1H), 3.16 - 3.09 (m, 2H), 3.07 - 2.98 (m, 2H), 2.22 - 2.09 (m, 2H). 13 C NMR (101 MHz, CDC13) δ 149.3, 139.6, 133.1, 129.5, 128.0, 126.9, 125.7, 125.6, 125.0, 119.4, 115.8, 42.4, 31.3, 25.6.

[0151] Preparation of the product obtained in Example 28, 3-(1,3-dithian-2-yl)-4-(6-methoxynaphthalen-2-yl)-1-phenyl-1H-pyrazole:

[0152] To a solution of dimethylsulfoxide (2 mL) was added 2-((6-methoxynaphthalen-2-yl)ethynyl)-1,3-dithiane (30 mg, 0.1 mmol), phenyl sydnone compound (16.3 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) successively. The resulting mixture was stirred vigorously at room temperature for 15 min. The mixture was quenched with water (5 mL) and extracted with ethyl acetate (10 mL x 3). The combined organic layer was washed with saturated brine (10 mL x 3) and dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated in vacuo. The product was obtained by column chromatography in 68% yield.

[0153] The structure and NMR data of the product obtained in Example 28, 3-(1,3-dithian-2-yl)-4-(6-methoxynaphthalen-2-yl)-1-phenyl-1H-pyrazole, are as follows:

[0154]

[0155] 3-(1,3-dithian-2-yl)-4-(6-methoxynaphthalen-2-yl)-1-phenyl-1H-pyrazole 1 H NMR (400 MHz, CDC13) δ 8.00 (s, 1H), 7.96 (d, J = 1.7 Hz, 1H), 7.84 - 7.80 (m, 2H), 7.80 - 7.77 (m, 2H), 7.64 (dd, J = 8.3, 1.8 Hz, 1H), 7.48 - 7.43 (m, 2H), 7.32 - 7.28 (m, 1H), 7.22 - 7.16 (m, 2H), 5.37 (s, 1H), 3.95 (s, 3H), 3.14 - 3.07 (m, 2H), 3.04 - 2.96 (m, 2H), 2.20 - 2.11 (m, 2H). 13 C NMR (101 MHz, CDC13) δ 158.0, 149.6, 139.9, 133.8, 129.7, 129.4, 129.2, 127.5, 127.4, 127.4, 127.2, 126.7, 125.4, 122.8, 119.4, 119.4, 105.8, 55.5, 42.6, 31.6, 25.5.

[0156] Preparation of the product obtained in Example 29, 3-(1,3-dithian-2-yl)-1-phenyl-1H-pyrazole:

[0157] 2-Ethynyl-1,3-dithiane (14.4 mg, 0.1 mmol), phenyl sydney ketone compound (16.3 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) were added sequentially to a dry dimethyl sulfoxide (2 ml) solution. The resulting mixture was vigorously stirred at room temperature for 15 minutes. The mixture was quenched with water (5 ml) and extracted with ethyl acetate (10 ml × 3). The combined organic layer was washed with saturated brine (10 ml × 3), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated in vacuo. The product was obtained by column chromatography with a yield of 68%.

[0158] The structure and NMR data of the product 3-(1,3-dithian-2-yl)-1-phenyl-1H-pyrazole obtained in Example 29 are as follows:

[0159]

[0160] 3-(1,3-Dithian-2-yl)-1-phenyl-1H-pyrazole 1 H NMR(400MHz, CDCl3)δ7.86(d,J=2.5Hz,1H),7.70–7.65(m,2H),7.43(dd,J=8.6,7.3Hz,2H),7.30–7.26(m,1H), 6.56(d,J=2.5Hz,1H),5.44(s,1H),3.10–3.02(m,2H),3.01–2.94(m,2H),2.21–2.15(m,1H),2.06–1.95(m,1H). 13 C NMR (101MHz, CDCl3) δ152.0,140.0,129.5,127.9,126.7,119.4,106.5,44.4,31.4,25.5.

[0161] Preparation of the product 3-(1,3-dithian-2-yl)-4-methyl-1-phenyl-1H-pyrazole obtained in Example 30:

[0162] 2-(Propan-1-yn-1-yl)-1,3-dithiane (15.8 mg, 0.1 mmol), phenyl syringone (16.3 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) were added sequentially to a solution of dry dimethyl sulfoxide (2 ml). The resulting mixture was vigorously stirred at room temperature for 15 minutes. The mixture was quenched with water (5 ml) and extracted with ethyl acetate (10 ml × 3). The combined organic layers were washed with saturated brine (10 ml × 3), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated in vacuo. The product was obtained by column chromatography with a yield of 71%.

[0163] The structure and NMR data of the product obtained in Example 30, 3-(1,3-dithian-2-yl)-4-methyl-1-phenyl-1H-pyrazole, are as follows:

[0164]

[0165] 3-(1,3-dithian-2-yl)-4-methyl-1-phenyl-1H-pyrazole 1 H NMR (400 MHz, CDC13) δ 7.67 - 7.62 (m, 3H), 7.42 - 7.37 (m, 2H), 7.25 - 7.19 (m, 1H), 5.37 (s, 1H), 3.06 - 3.00 (m, 4H), 2.23 (s, 3H), 2.21 - 2.13 (m, 1H), 2.11 - 1.98 (m, 1H). 13 C NMR (101 MHz, CDC13) δ 150.1, 140.0, 129.3, 126.6, 126.1, 118.9, 116.5, 43.5, 31.4, 25.6, 8.9.

[0166] Preparation of the product obtained in Example 31, 1-(4-chlorophenyl)-3-(1,3-dithian-2-yl)-4-methyl-1H-pyrazole:

[0167] To a solution of dry dimethyl sulfoxide (2 mL) was added 2-(prop-1-yn-1-yl)-1,3-dithiane (15.8 mg, 0.1 mmol), the corresponding sylvanone compound (19.6 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) successively. The resulting mixture was stirred vigorously at room temperature for 15 min. The mixture was quenched with water (5 mL) and extracted with ethyl acetate (10 mL x 3). The combined organic layers were washed with saturated brine (10 mL x 3) and dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated in vacuo. The product was obtained by column chromatography in 73% yield.

[0168] The structure and NMR data of the product obtained in Example 31, 1-(4-chlorophenyl)-3-(1,3-dithian-2-yl)-4-methyl-1H-pyrazole, are as follows:

[0169]

[0170] 1-(4-chlorophenyl)-3-(1,3-dithian-2-yl)-4-methyl-1H-pyrazole 1H NMR (400 MHz, CDC13) δ 7.63 - 7.55 (m, 3H), 7.40 - 7.32 (m, 2H), 5.34 (s, 1H), 3.08 - 3.00 (m, 4H), 2.21 (s, 3H), 2.20 - 2.13 (m, 1H), 2.12 - 1.96 (m, 1H). 13 C NMR (101 MHz, CDC13) δ 150.5, 138.6, 131.5, 129.4, 126.5, 120.0, 116.9, 43.4, 31.4, 25.5, 8.8

[0171] Preparation of the product 1 -(4-bromophenyl)-3-(1,3-dithian-2-yl)-4-methyl- 1 H-pyrazole from Example 32:

[0172] To a solution of dry dimethylsulfoxide (2 mL) was added 2-(prop-1 -yn-1 -yl)-1,3-dithiane (15.8 mg, 0.1 mmol), the corresponding sylvanoid compound (23.9 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) sequentially. The resulting mixture was stirred vigorously at room temperature for 15 min. The mixture was quenched with water (5 mL) and extracted with ethyl acetate (10 mL x 3). The combined organic layers were washed with saturated brine (10 mL x 3) and dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated in vacuo. The product was obtained in 70% yield by column chromatography.

[0173] The structure and NMR data of the product 1 -(4-bromophenyl)-3-(1,3-dithian-2-yl)-4-methyl- 1 H-pyrazole from Example 32 are as follows:

[0174]

[0175] 1 -(4-bromophenyl)-3-(1,3-dithian-2-yl)-4-methyl- 1 H-pyrazole 1 H NMR (400 MHz, CDC13) δ 7.63 - 7.55 (m, 3H), 7.40 - 7.32 (m, 2H), 5.34 (s, 1H), 3.08 - 3.00 (m, 4H), 2.21 (s, 3H), 2.20 - 2.13 (m, 1H), 2.12 - 1.96 (m, 1H). 13 C NMR (101 MHz, CDC13) δ 150.5, 138.6, 131.5, 129.4, 126.5, 120.0, 116.9, 43.4, 31.4, 25.5, 8.8

[0176] Preparation of the product 3-(1,3-dithian-2-yl)-4-ethyl-1 -phenyl-1 H-pyrazole from Example 33:

[0177] To a solution of dry dimethylsulfoxide (2 mL) was added 2-(but-1-yn-1-yl)-1,3-dithiane (17.2 mg, 0.1 mmol), phenyl sydnone compound (16.3 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) successively. The resulting mixture was stirred vigorously at room temperature for 15 min. The mixture was quenched with water (5 mL) and extracted with ethyl acetate (10 mL x 3). The combined organic layers were washed with saturated brine (10 mL x 3) and dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated in vacuo. The product was obtained in 67% yield by column chromatography.

[0178] The structure and NMR data of the product 3-(1,3-dithian-2-yl)-4-ethyl-1 -phenyl-1 H-pyrazole from Example 33 are as follows:

[0179]

[0180] 3-(1,3-dithian-2-yl)-4-ethyl-1 -phenyl-1 H-pyrazole 1 H NMR (400 MHz, CDCI3) δ 7.69 - 7.63 (m, 3H), 7.43 - 7.36 (m, 2H), 7.25 - 7.19 (m, 1 H), 5.35 (s, 1 H), 3.05 - 3.00 (m, 4H), 2.69 - 2.62 (m, 2H), 2.20 - 2.13 (m, 1 H), 2.10 - 1.99 (m, 1 H), 1.30 - 1.24 (m, 3H). 13 C NMR (101 MHz, CDCI3) δ 149.5, 140.0, 129.3, 126.1, 125.4, 123.5, 118.9, 43.5, 31.5, 25.5, 17.1, 14.8.

[0181] Preparation of the product 3-(1,3-dithian-2-yl)-4-pentyl-1 -phenyl-1 H-pyrazole from Example 34:

[0182] To a solution of dimethylsulfoxide (2 mL) was added 2-(hept-1-yn-1-yl)-1,3-dithiane (21.4 mg, 0.1 mmol), phenyl sydnone compound (16.3 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) successively. The resulting mixture was stirred vigorously at room temperature for 15 min. The mixture was quenched with water (5 mL) and extracted with ethyl acetate (10 mL x 3). The combined organic layers were washed with saturated brine (10 mL x 3) and dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated in vacuo. The product was obtained by column chromatography in 68% yield.

[0183] The structure and NMR data of the product obtained in Example 34, 3-(1,3-dithian-2-yl)-4-pentyl-1-phenyl-1H-pyrazole, are as follows:

[0184]

[0185] 3-(1,3-dithian-2-yl)-4-pentyl-1-phenyl-1H-pyrazole 1 H NMR (400 MHz, CDC13) δ 7.70 - 7.62 (m, 3H), 7.39 (t, J = 7.9 Hz, 2H), 7.22 (t, J = 7.4 Hz, 1H), 5.33 (s, 1H), 3.03 (dd, J = 7.3, 4.0 Hz, 4H), 2.63 - 2.57 (m, 2H), 2.21 - 2.13 (m, 1H), 2.11 - 1.98 (m, 1H), 1.68 - 1.63 (m, 2H), 1.42 - 1.35 (m, 4H), 0.95 - 0.90 (m, 3H). 13 C NMR (101 MHz, CDC13) δ 149.8, 140.1, 129.3, 126.1, 125.7, 121.9, 118.9, 43.4, 31.7, 31.5, 30.1, 25.6, 23.7, 22.6, 14.2

[0186] Preparation of the product obtained in Example 35, 3-(bis(ethylthio)methyl)-1,4-diphenyl-1H-pyrazole:

[0187] To a solution of dimethylsulfoxide (2 mL) was added (3-phenylprop-2-yn-1,1-diyl)bis(ethylsulfane) (23.6 mg, 0.1 mmol), phenyl sydnone compound (16.3 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) successively. The resulting mixture was stirred vigorously at room temperature for 15 min. The mixture was quenched with water (5 mL) and extracted with ethyl acetate (10 mL x 3). The combined organic layers were washed with saturated brine (10 mL x 3) and dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated in vacuo. The product was obtained in 69% yield after column chromatography.

[0188] The structure and NMR data of the product obtained in Example 35, 3-(bis(ethylthio)methyl)-1,4-diphenyl-1H-pyrazole, are as follows:

[0189]

[0190] 3-(bis(ethylthio)methyl)-1,4-diphenyl-1H-pyrazole 1 H NMR (400 MHz, CDC13) δ 7.92 (s, 1H), 7.76 - 7.68 (m, 2H), 7.59 - 7.52 (m, 2H), 7.48 - 7.41 (m, 4H), 7.37 - 7.27 (m, 2H), 5.20 (s, 1H), 2.91 - 2.68 (m, 4H), 1.23 (t, J = 7.4 Hz, 6H). 13 C NMR (101 MHz, CDC13) δ 150.4, 140.0, 132.4, 129.5, 129.0, 128.8, 127.3, 126.6, 125.6, 122.4, 119.2, 45.3, 25.4, 14.3.

[0191] Preparation of the product obtained in Example 36, 1-(4-bromo-3-chlorophenyl)-4- phenyl-1H-pyrazole-3-carbaldehyde:

[0192] To a solution of dimethylsulfoxide (2 mL) was added (3-phenylprop-2-yn-1,1-diyl)bis(ethylsulfane) (23.6 mg, 0.1 mmol), phenyl sydnone compound (16.3 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) successively. The resulting mixture was stirred vigorously at room temperature for 15 min. The mixture was quenched with water (5 mL) and extracted with ethyl acetate (10 mL x 3). The combined organic layers were washed with saturated brine (10 mL x 3) and dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated in vacuo. The product was obtained in 69% yield after column chromatography.

[0188] The structure and NMR data of the product obtained in Example 35, 3-(bis(ethylthio)methyl)-1,4-diphenyl-1H-pyrazole, are as follows:

[0189]

[0190] 3-(bis(ethylthio)methyl)-1,4-diphenyl-1H-pyrazole 1 H NMR (400 MHz, CDC13) δ 7.92 (s, 1H), 7.76 - 7.68 (m, 2H), 7.59 - 7.52 (m, 2H), 7.48 - 7.41 (m, 4H), 7.37 - 7.27 (m, 2H), 5.20 (s, 1H), 2.91 - 2.68 (m, 4H), 1.23 (t, J = 7.4 Hz, 6H). 13 C NMR (101 MHz, CDC13) δ 150.4, 140.0, 132.4, 129.5, 129.0, 128.8, 127.3, 126.6, 125.6, 122.4, 119.2, 45.3, 25.4, 14.3.

[0191] Preparation of the product obtained in Example 36, 1-(4-bromo-3-chlorophenyl)-4- phenyl-1H-pyrazole-3-carbaldehyde:

[0192] To a solution of dimethylsulfoxide (2 mL) was added (3-phenylprop-2-yn-1,1-diyl)bis(ethylsulfane) (23.6 mg, 0.1 mmol), phenyl sydnone compound (16.3 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) successively. The resulting mixture was stirred vigorously at room temperature for 15 min. The mixture was quenched with water (5 mL) and extracted with ethyl acetate (10 mL x 3). The combined organic layers were washed with saturated brine (10 mL x 3) and dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated in vacuo. The product was obtained in 69% yield after column chromatography.

[0193] The structure and NMR data of the product 1-(4-bromo-3-chlorophenyl)-4-phenyl-1H-pyrazole-3-carbaldehyde obtained in Example 36 are as follows:

[0194]

[0195] 1-(4-Bromo-3-chlorophenyl)-4-phenyl-1H-pyrazole-3-carbaldehyde 1 H NMR (400MHz, CDCl3) δ10.16(s,1H),8.04(s,1H),7.97(d,J=2.5Hz,1H),7.75(dd,J=8.8,1.7Hz,1H),7.64–7.56(m,3H),7.46–7.37(m,3H). 13 C NMR (101MHz, CDCl3) δ186.5,148.3,139.1,136.1,134.8,129.9,129.0,128.7,128.4,127.5,127.4,121.7,121.4,118.8

[0196] Preparation of the product 3-methyl-1,4-diphenyl-1H-pyrazole obtained in Example 37:

[0197] 3-(1,3-dithian-2-yl)-1,4-diphenyl-1H-pyrazole (34 mg, 0.1 mmol) was dissolved in dry tetrahydrofuran (5 ml). An excess of Raney nickel was added to this solution. The resulting mixture was vigorously stirred at room temperature until 3-(1,3-dithian-2-yl)-1,4-diphenyl-1H-pyrazole disappeared as determined by TLC analysis. The reaction mixture was filtered, washed with dichloromethane, and extracted with dichloromethane (15 mL × 3). The organic layers were combined and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated in vacuo and purified by column chromatography to obtain the product in a yield of 70%.

[0198] The structure and NMR data of the product 3-methyl-1,4-diphenyl-1H-pyrazole obtained in Example 37 are as follows:

[0199]

[0200] 3-Methyl-1,4-diphenyl-1H-pyrazole 1 H NMR (400MHz, CDCl3) δ7.96(s,1H),7.73–7.65(m,2H),7.50–7.38(m,6H),7.33–7.23(m,2H),2.50(s,3H). 13C NMR (101 MHz, CDC13) δ 148.1, 140.1, 133.2, 129.6, 128.8, 127.8, 126.7, 126.2, 125.3, 123.5, 118.9, 13.5

[0201] Preparation of the product 3-(difluoromethyl)-l,4-diphenyl-lH-pyrazole from Example 38:

[0202] In a 15 ml centrifuge tube, a suspension of N-iodosuccinimide (NIS) (2 aliquots) in 0.5 ml of dichloromethane was cooled to -78 °C and stirred for 10 minutes. To the mixture was added pyridine hydrofluoride (4 aliquots) dropwise and stirred for 5 minutes at -78 °C. Then, a solution of 3-(l,3-dithian-2-yl)-l,4-diphenyl-lH-pyrazole in 0.5 ml of dichloromethane was added dropwise. After the reaction was determined to be complete by TLC, the mixture was warmed to ambient temperature, quenched by dropwise addition of saturated sodium bicarbonate solution (5 ml), and the mixture was stirred for 10 minutes until no gas bubbles were observed. The mixture was extracted with dichloromethane (5 ml x 3), washed with saturated brine (5 ml), and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated in vacuo and purified by column chromatography to give the product in 50% yield.

[0203] The structure and NMR data of the product 3-(difluoromethyl)-l,4-diphenyl-lH-pyrazole from Example 38 are as follows:

[0204]

[0205] 3-(difluoromethyl)-l,4-diphenyl-lH-pyrazole 1 H NMR (400 MHz, CDC13) δ 8.05 (s, 1H), 7.77 - 7.70 (m, 2H), 7.60 - 7.55 (m, 2H), 7.50 (t, J = 8.0 Hz, 2H), 7.47 - 7.41 (m, 2H), 7.40 - 7.33 (m, 2H), 6.86 (t, J = 54.0 Hz, 1H). 13 C NMR (101 MHz, CDC13) δ 144.3 (t, J = 27.8 Hz), 139.5, 130.9, 129.8, 128.9, 128.5 (d, J = 3.9 Hz), 127.8, 127.6, 126.9, 123.9, 119.6, 112.0 (t, J = 234.5 Hz). 19 F NMR (377 MHz, CDC13) δ -110.22, -110.36.

[0206] Preparation of the product 3-((1-(3,5-dichlorophenyl)-4-phenyl-1H-pyrazol-3-yl)methyl)-1H- indole from Example 39:

[0207] To a magnetically stirred solution of 1-(3,5-dichlorophenyl)-3-(1,3-dithiol-2-yl)-4-phenyl- 1H-pyrazole (40 mg, 0.1 mmol) and indole (12 mg, 0.1 mmol) in dichloromethane (10 mL) was added iodine (30 mg, 0.12 mmol) and dimethylsilane (28 mg, 0.3 mmol). The resulting mixture was stirred vigorously at room temperature for 12 h, and the completion of the reaction was monitored by TLC. The mixture was quenched with saturated sodium bisulfite solution (10 mL) and extracted with dichloromethane (15 mL). The organic layer was separated and the aqueous phase was re-extracted with dichloromethane (15 mL x 3). The combined organic extracts were washed with brine (15 mL x 3) and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated in vacuo and purified by column chromatography to give the pure desired product in 58% yield.

[0208] The structure and NMR data of the product 3-((1-(3,5-dichlorophenyl)-4-phenyl-1H- pyrazol-3-yl)methyl)-1H-indole from Example 39 are as follows:

[0209]

[0210] 3-((1-(3,5-dichlorophenyl)-4-phenyl-1H-pyrazol-3-yl)methyl)-1H-indole 1 H NMR (400 MHz, CDC13) δ 8.38 (bis, 1H), 8.12 - 8.03 (m, 2H), 7.76 (dd, J = 8.1, 1.4 Hz, 1H), 7.73 - 7.64 (m, 1H), 7.54 - 7.48 (m, 2H), 7.45 (d, J = 8.0 Hz, 1H), 7.33 - 7.27 (m, 1H), 7.20 - 7.14 (m, 1H), 7.13 (d, J = 2.5 Hz, 1H), 6.92 - 6.85 (m, 1H), 6.57 (dd, J = 8.0, 1.3 Hz, 1H), 6.42 - 6.33 (m, 1H), 6.19 (dd, J = 7.6, 1.6 Hz, 1H), 4.27 (s, 2H). 13 C NMR (101 MHz, CDC13) δ 160.9, 146.6, 146.6, 138.7, 136.1, 130.7, 129.3, 128.7, 127.5, 126.3, 124.4, 124.0, 122.8, 120.7, 119.7, 117.7, 116.0, 115.3, 111.6, 40.0.

[0211] Preparation of the product from Example 40, 2-(l-(3,5-dichlorophenyl)-4-phenyl-lH- pyrazol-3-yl)-l,3-dithiane 1,1,3,3-tetraoxide:

[0212] l-(3,5-dichlorophenyl)-3-(l,3-dithiolan-2-yl)-4-phenyl-lH-pyrazole (40 mg, 0.1 mmol) was dissolved in dichloroethane (4 mL), m-CPBA (103 mg, 0.6 mmol) was dissolved in dichloroethane (4 mL), then the m-CPBA solution was added to l-(3,5-dichlorophenyl)-3-(l,3-dithiolan-2-yl)-4-phenyl-lH-pyrazole in an ice bath and stirred at room temperature for 48 hours. The two phases were separated and the aqueous phase was extracted into dichloromethane (15 mL x 3). The combined organic phases were dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated in vacuo and purified by column chromatography to give the pure desired product in 67% yield.

[0213] The structure and NMR data of the product from Example 40, 2-(l-(3,5-dichlorophenyl)-4-phenyl-lH-pyrazol-3-yl)-l,3-dithiane 1,1,3,3-tetraoxide, are as follows:

[0214]

[0215] 2-(l-(3,5-dichlorophenyl)-4-phenyl-lH-pyrazol-3-yl)-l,3-dithiane 1,1,3,3-tetraoxide 1 HNMR (400 MHz, DMSO) δ 9.07 (s, 1H), 8.14 (d, J = 1.8 Hz, 2H), 7.68 (s, 1H), 7.65 - 7.53 (m, 4H), 7.53 - 7.44 (m, 1H), 6.15 (s, 1H), 3.93 - 3.74 (m, 4H), 2.56 - 2.48 (m, 2H). 13 C NMR (101 MHz, DMSO) δ 141.0, 135.7, 130.4, 129.6, 129.2, 129.0, 128.6, 128.5, 127.1, 117.8, 78.3, 50.0, 18.1.

Claims

1. A 1,3-dithiane-substituted pyrazole derivative, characterized in that The 1,3-dithiane-substituted pyrazole derivative has the following structure (I): R in structure (Ⅰ) 1 is hydrogen, methyl, ethyl, substituted phenyl, naphthyl, benzofuranyl, or thienyl, wherein the substituent in the substituted phenyl is selected from one or more of hydrogen, methoxy, fluorine, chlorine, and trifluoromethoxy; R 2 The substituted phenyl group or benzodioxolane group is selected from one or more of hydrogen, methoxy, fluorine, chlorine, bromine and trifluoromethoxy.

2. The method for preparing a 1,3-dithiane-substituted pyrazole derivative according to claim 1, characterized in that: The method comprises the following steps: reacting a 2-ethynyl-1,3-dithiane derivative (II) and a Sydney ketone compound (III) in a suitable organic solvent under the action of a base to generate a pyrazole compound (I). The chemical reaction equation is as follows:

3. The preparation method according to claim 2, characterized in that The organic solvent is one of dimethyl sulfoxide (DMSO) and N,N-dimethylformamide (DMF); the base is one of potassium tert-butoxide, sodium tert-butoxide and sodium methoxide.

4. The preparation method according to claim 2, characterized in that The molar ratio of the base, the 2-ethynyl-1,3-dithiane derivative (II) and the Sydney ketone compound (III) is 2:1:

1.

5. Use of a 1,3-dithiane-substituted pyrazole derivative in the synthesis of an aldehyde-substituted pyrazole compound according to claim 1, characterized in that: The method comprises the following steps: adding a 1,3-dithiane-substituted pyrazole derivative (I), acetonitrile and water into a reaction vessel, adding [bis(trifluoroacetoxy)iodo]benzene (PIFA) at 0°C, and reacting at room temperature to obtain the target product IV. The chemical reaction equation is as follows:

6. Use of a 1,3-dithiane-substituted pyrazole derivative in the synthesis of a methyl-substituted pyrazole compound according to claim 1, characterized in that: The method comprises the following steps: adding dry tetrahydrofuran and a 1,3-dithiane-substituted pyrazole derivative (I) into a reaction vessel, adding Raney nickel (Raney-Ni) in batches, and reacting at room temperature to obtain the target product V. The chemical reaction equation is as follows:

7. Use of a 1,3-dithiane-substituted pyrazole derivative in the synthesis of a fluorine-substituted pyrazole compound according to claim 1, characterized in that: The method comprises the following steps: adding N-iodosuccinimide (NIS), pyridine hydrofluoride, and a 1,3-dithiane-substituted pyrazole derivative (I) into a reaction vessel, and reacting at -78°C to obtain the target product VI. The chemical reaction equation is as follows:

8. Use of a 1,3-dithiane-substituted pyrazole derivative in the synthesis of an indole-substituted pyrazole compound according to claim 1, characterized in that: The method comprises the following steps: adding indole, iodine, dimethyl monochlorosilane and a 1,3-dithiane-substituted pyrazole derivative (I) into a reaction vessel, and reacting at room temperature to obtain the target product VI. The chemical reaction equation is as follows:

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