1, 3-dithiane substituted pyrazole derivative as well as preparation method and application thereof

Abstract

The invention 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. Alkynyl thiane compounds and sydnone compounds are used as raw materials, and intermolecular cycloaddition is carried out under the promotion of alkali to obtain the compound. The compound is structurally characterized in that the compound has a structure shown in a formula (I), R1 is alkyl or aryl, and R2 is aryl. According to the method provided by the invention, cheap alkali is used as an accelerant, a noble metal catalyst is not used, the reaction condition is mild, the operation is simple, the substrate applicability is wide, the regioselectivity is high, meanwhile, efficient functionalization is carried out on C-3 sites, which do not have reaction activity, of a pyrazol framework, and the method has very strong practicability and industrial application prospects. The method provided by the invention can be used for synthesis and later modification of natural products, drug molecules and functional material molecules.

Description

Technical Field

[0001] The invention 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. Technical Background

[0002] Pyrazole derivatives have a variety of 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 structures of several drugs approved by the U.S. Food and Drug Administration (FDA) (such as Celebrex, Lonazolac, Acomplia, etc.) (Chem.Rev.2021,121(3),1670-1715.). The [3+2] cycloaddition reaction of Sydney ketone with alkyne compounds has become one of the most effective methods for constructing pyrazole rings.

[0003] Therefore, the synthesis of pyrazole compounds by Sydney ketone and alkyne shows important application value in many fields such as medicine, biology, and materials. However, so far, the synthesis of this type of skeleton mainly has the following disadvantages, 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-precious metal catalysis, mild conditions, and simple operation.

[0004] As an aldehyde and ketone protecting group and polar conversion reagent, 1,3-dithiane can couple acyl carbon with electrophiles and form carbon-carbon (CC) bonds, playing 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.). Drug molecules substituted with 1,3-dithiane can consume ROS (reactive oxygen species) and reduce oxidative stress in vivo (ACSNano.2022,16,21225-21239). At the same time, the introduced sulfur atom can change the lipid solubility, metabolic stability and bioavailability of drug molecules, thereby optimizing the pharmacokinetic properties of drugs. Summary of the invention

[0005] The purpose of the present invention is to provide a 1,3-dithiane substituted pyrazole derivative and a preparation method and application thereof, that is, 2-ethynyl-1,3-dithiane derivative, Sydney ketone compound, suitable solvent and base are added in sequence in a reactor, and reacted at room temperature to obtain a class of pyrazole compounds. The method does not require precious metal catalysis, does not require anhydrous and oxygen-free operation, has mild conditions, wide substrate applicability, high regional selectivity and high yield.

[0006] The present invention relates to a 1,3-dithiane-substituted pyrazole derivative and a preparation method and application thereof, wherein the 1,3-dithiane-substituted pyrazole derivative has the following structure (I):

[0007] In structure (Ⅰ), R 1 is an aliphatic substituent (the substituent is selected from hydrogen, methyl, ethyl, etc.), a substituted phenyl (the substituent is selected from one or more of hydrogen, methoxy, fluorine, chlorine, trifluoromethoxy), naphthyl, benzofuranyl, thienyl, etc.; R 2 It is a substituted phenyl group (the substituent is selected from one or more of hydrogen, methoxy, fluorine, chlorine, bromine and trifluoromethoxy), or a benzodioxolane group.

[0008] The present invention relates to a method for preparing a 1,3-dithiane-substituted pyrazole derivative, which is characterized by comprising 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), wherein the chemical reaction equation is as follows:

[0009] In the above technical solution, the organic solvent is one of dimethyl sulfoxide (DMSO) and N,N-dimethylformamide (DMF).

[0010] The base is one of potassium tert-butoxide, sodium tert-butoxide and sodium methoxide.

[0011] In the above technical solution, the molar ratio of the base, the 2-ethynyl-1,3-dithiane derivative (II) and the Sydney ketone compound (III) is 2:1:1.

[0012] In the above technical scheme, the specific reaction steps include: adding 2-ethynyl-1,3-dithiane derivatives, Sydney ketone compounds, suitable solvents and bases to the reaction flask in sequence, stirring the reaction at room temperature for 15 minutes, monitoring the reaction by thin layer chromatography, and slowly adding saturated brine to the reaction system to quench the reaction after the raw materials are completely consumed, and extracting three times with ethyl acetate (15 ml), combining the organic phases, washing the organic phases three times with saturated brine (40 ml), drying over anhydrous sodium sulfate, filtering, removing volatiles under vacuum, and obtaining the product by column chromatography. DETAILED DESCRIPTION

[0013] The following examples can help those skilled in the art to more fully understand the present invention, but they do not limit the present invention in any way. The raw materials used in the present invention are all known compounds, which can be purchased from the market or synthesized using methods known in the art.

[0014] Example 1: Preparation of compound 3-(1,3-dithiane-2-yl)-1,4-diphenyl-1H-pyrazole:

[0015] 2-(Phenylethynyl)-1,3-dithiane (22 mg, 0.1 mmol), phenyl sydney ketone (16.3 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) were added to a dry dimethyl sulfoxide (2 ml) solution. 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 × 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 72%.

[0016] The structure and NMR data of the product 3-(1,3-dithiane-2-yl)-1,4-diphenyl-1H-pyrazole obtained in Example 1 are as follows:

[0017]

[0018] 3-(1,3-Dithian-2-yl)-1,4-diphenyl-1H-pyrazole 1 H NMR (400MHz, CDCl3) δ7.92(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 (101MHz, CDCl3) δ149.4,139.9,132.2,129.4,129.0,128.6,127.4,126.7,125.4,122.7,119.4,42.4,31.5,25.5.

[0019] Example 2: Preparation of compound 3-(1,3-dithian-2-yl)-1-(4-fluorophenyl)-4-phenyl-1H-pyrazole:

[0020] 2-(Phenylethynyl)-1,3-dithiane (22 mg, 0.1 mmol), the corresponding Sydney ketone compound (18 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) were added 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 70%.

[0021] The structure and NMR data of the product 3-(1,3-dithian-2-yl)-1-(4-fluorophenyl)-4-phenyl-1H-pyrazole obtained in Example 2 are as follows:

[0022]

[0023] 3-(1,3-Dithian-2-yl)-1-(4-fluorophenyl)-4-phenyl-1H-pyrazole 1 H NMR(400MHz, CDCl3)δ7.86(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 (101MHz, CDCl3) δ161.38 (d, J = 247.4Hz), 149.4, 136.2, 132.1, 129.0, 128.6, 127.4, 125.5, 122.8, 121.2 (d, J = 8.3Hz), 116.2 (d, J = 22.9Hz), 42.5, 31.7, 25.5. 19 F NMR (377MHz,CDCl3)δ-115.7.

[0024] Preparation of the product obtained in Example 3: 3-(1,3-dithiane-2-yl)-1-(4-chlorophenyl)-4-phenyl-1H-pyrazole:

[0025] 2-(Phenylethynyl)-1,3-dithiane (22 mg, 0.1 mmol), the corresponding Sydney ketone compound (19.6 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) were added 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 75%.

[0026] The structure and NMR data of the product 3-(1,3-dithian-2-yl)-1-(4-chlorophenyl)-4-phenyl-1H-pyrazole obtained in Example 3 are as follows:

[0027]

[0028] 3-(1,3-Dithian-2-yl)-1-(4-chlorophenyl)-4-phenyl-1H-pyrazole 1 H NMR(400MHz, CDCl3)δ7.88(s,1H),7.70(d,J=8.9Hz,2H),7.57–7.52(m,2H),7.49–7.43(m,2 H),7.43–7.39(m,2H),7.39–7.33(m,1H),5.29(s,1H),3.11–2.96(m,4H),2.21–2.06(m,2H). 13 C NMR (101MHz, CDCl3) δ149.7,138.4,132.2,131.9,129.5,129.0,128.6,127.5,125.3,123.1,120.5,42.5,31.6,25.5.

[0029] Example 4 Preparation of the product 3-(1,3-dithian-2-yl)-1-(4-bromophenyl)-4-phenyl-1H-pyrazole:

[0030] 2-(Phenylethynyl)-1,3-dithiane (22 mg, 0.1 mmol), the corresponding Sydney ketone compound (23.9 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) were added 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 73%.

[0031] The structure and NMR data of the product 3-(1,3-dithian-2-yl)-1-(4-bromophenyl)-4-phenyl-1H-pyrazole obtained in Example 4 are as follows:

[0032]

[0033] 3-(1,3-Dithian-2-yl)-1-(4-bromophenyl)-4-phenyl-1H-pyrazole 1 H NMR (400MHz, CDCl3) δ7.88(s,1H),7.64(d,J=8.8Hz,2H),7.58–7.55(m,2H),7.53(d,J=2.5Hz,2 H),7.45(t,J=7.6Hz,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 (101MHz, CDCl3) δ149.7,138.8,132.5,131.9,129.0,128.6,127.5,125.2,123.1,120.7,120.0,42.4,31.6,25.4.

[0034] Example 5 Preparation of the product 4-(3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazol-1-yl)benzonitrile:

[0035] 2-(Phenylethynyl)-1,3-dithiane (22 mg, 0.1 mmol), the corresponding Sydney ketone compound (18.7 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) were added 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 75%.

[0036] 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:

[0037]

[0038] 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.

[0039] Example 6 Preparation of the product 3-(1,3-dithian-2-yl)-4-phenyl-1-(4-(trifluoromethoxy)phenyl)-1H-pyrazole:

[0040] 2-(Phenylethynyl)-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 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 67%.

[0041] The structure and NMR data of the product 3-(1,3-dithian-2-yl)-4-phenyl-1-(4-(trifluoromethoxy)phenyl)-1H-pyrazole obtained in Example 6 are as follows:

[0042]

[0043] 3-(1,3-Dithian-2-yl)-4-phenyl-1-(4-(trifluoromethoxy)phenyl)-1H-pyrazole 1HNMR(400MHz, CDCl3)δ7.89(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=8.7Hz,2H),5.29(s,1H),3.11–2.95(m,4H),2.21–2.07(m,2H). 13 C NMR (101MHz, CDCl3) δ149.9, 147.5, 138.3, 131.9, 129.0, 128.6, 127.6, 125.4, 123.2, 122.1, 120.6 (q, J = 257.2Hz), 120.5, 42.4, 31.6, 25.5. 19 F NMR (377 MHz, CDCl3) δ-58.0.

[0044] Example 7 Preparation of the product 3-(1,3-dithian-2-yl)-4-phenyl-1-(4-(trifluoromethyl)phenyl)-1H-pyrazole:

[0045] 2-(Phenylethynyl)-1,3-dithiane (22 mg, 0.1 mmol), the corresponding Sydney ketone compound (23 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) were added 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 69%.

[0046] The structure and NMR data of the product 3-(1,3-dithian-2-yl)-4-phenyl-1-(4-(trifluoromethyl)phenyl)-1H-pyrazole obtained in Example 7 are as follows:

[0047]

[0048] 3-(1,3-Dithian-2-yl)-4-phenyl-1-(4-(trifluoromethyl)phenyl)-1H-pyrazole 1 H NMR(400MHz, CDCl3)δ7.97(s,1H),7.88(d,J=8.5Hz,2H),7.69(d,J=8.5Hz,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(101MHz, CDCl3)δ150.4,142.1,131.7,128.9,128.6,128.5(q,J=32.8Hz)127. 7,126.8(q,J=3.7Hz),125.3,124.1(q,J=271.9Hz),123.6,118.9,42.3,31.5,25.4. 19 F NMR (377 MHz, CDCl3) δ-62.2.

[0049] Preparation of the product obtained in Example 8: 3-(1,3-dithian-2-yl)-4-phenyl-1-(4-(methyloxy)phenyl)-1H-pyrazole:

[0050] 2-(Phenylethynyl)-1,3-dithiane (22 mg, 0.1 mmol), the corresponding Sydney ketone compound (19.2 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) were added 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 65%.

[0051] The structure and NMR data of the product 3-(1,3-dithian-2-yl)-4-phenyl-1-(4-(methoxy)phenyl)-1H-pyrazole obtained in Example 8 are as follows:

[0052]

[0053] 3-(1,3-Dithian-2-yl)-4-phenyl-1-(4-(methyloxy)phenyl)-1H-pyrazole 1 H NMR (400MHz, CDCl3) δ7.82 (s, 1H), 7.65 (d, J = 9.0Hz, 2H), 7.59–7.51 (m, 2H), 7.49–7.41 (m, 2H), 7.3 9–7.31(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 (101MHz, CDCl3) δ158.5,148.8,133.7,132.4,129.0,128.6,127.3,125.4,122.3,121.1,114.5,55.7,42.6,31.7,25.5.

[0054] Preparation of the product obtained in Example 9: 1-(3,5-dichlorophenyl)-3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazole:

[0055] 2-(Phenylethynyl)-1,3-dithiane (22 mg, 0.1 mmol), the corresponding Sydney ketone compound (23 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) were added 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 72%.

[0056] The structure and NMR data of the product 1-(3,5-dichlorophenyl)-3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazole obtained in Example 9 are as follows:

[0057]

[0058] 1-(3,5-dichlorophenyl)-3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazole 1 H NMR(400MHz, CDCl3)δ7.88(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(101MHz, CDCl3)δ150.4,141.1,135.9,131.5,129.1,128.6,127.7,126.5,125.3,123.7,117.6,42.4,31.6,25.4.

[0059] Preparation of the product 1-(3-chlorophenyl)-3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazole obtained in Example 10:

[0060] 2-(Phenylethynyl)-1,3-dithiane (22 mg, 0.1 mmol), the corresponding Sydney ketone compound (19.6 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) were added 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 71%.

[0061] The structure and NMR data of the product 1-(3-chlorophenyl)-3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazole obtained in Example 10 are as follows:

[0062]

[0063] 1-(3-Chlorophenyl)-3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazole 1 H NMR (400MHz, CDCl3) δ7.90 (s, 1H), 7.82 (t, J = 2.1Hz, 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 (101MHz, CDCl3) δ149.9,140.7,135.3,131.8,130.4,129.0,128.6,127.6,126.7,125.3,123.2,119.6,117.1,42.4,31.6,25.5.

[0064] Preparation of the product 1-(3-bromophenyl)-3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazole obtained in Example 11:

[0065] 2-(Phenylethynyl)-1,3-dithiane (22 mg, 0.1 mmol), the corresponding Sydney ketone compound (24 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) were added 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 71%.

[0066] The structure and NMR data of the product 1-(3-bromophenyl)-3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazole obtained in Example 11 are as follows:

[0067]

[0068] 1-(3-Bromophenyl)-3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazole 1 H NMR (400MHz, CDCl3) δ8.00–7.95(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(101MHz, CDCl3)δ149.9,140.8,131.8,130.7,129.7,129.0,128.6,127.6,125.4,123.2,123.2,122.4,117.6,42.5,31.6,25.5.

[0069] Preparation of the product 1-(3-methoxyphenyl)-3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazole obtained in Example 12:

[0070] 2-(Phenylethynyl)-1,3-dithiane (22 mg, 0.1 mmol), the corresponding Sydney ketone compound (19.2 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) were added 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%.

[0071] The structure and NMR data of the product 1-(3-methoxyphenyl)-3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazole obtained in Example 12 are as follows:

[0072]

[0073] 1-(3-Methoxyphenyl)-3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazole. 1H NMR (400MHz, CDCl3) δ7.90 (s, 1H), 7.58–7.54 (m, 2H), 7.45 (t, J = 7.6Hz, 2H), 7.37–7.28 (m, 4H), 6.8 5–6.81(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 (101MHz, CDCl3) δ160.6,149.4,141.1,132.2,130.2,129.0,128.6,127.4,125.6,122.7,112.5,111.6,105.6,55.7,42.4,31.5,25.5.

[0074] Preparation of the product obtained in Example 13: 1-(4-bromo-3-chlorophenyl)-3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazole:

[0075] 2-(Phenylethynyl)-1,3-dithiane (22 mg, 0.1 mmol), the corresponding Sydney ketone compound (27.3 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) were added 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 70%.

[0076] The structure and NMR data of the product 1-(4-bromo-3-chlorophenyl)-3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazole obtained in Example 13 are as follows:

[0077]

[0078] 1-(4-Bromo-3-chlorophenyl)-3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazole 1 H NMR (400MHz, CDCl3) δ7.94–7.91(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 (101MHz, CDCl3) δ150.2,139.6,135.6,134.3,131.6,129.0,128.6,127.7,125.2,123.6,120.9,119.9,118.2,42.4,31.6,25.4.

[0079] Preparation of the product 1-(4-chlorophenyl)-3-(1,3-dithian-2-yl)-1H-pyrazole obtained in Example 14:

[0080] 2-Ethynyl-1,3-dithiane (14.4 mg, 0.1 mmol), the corresponding Sydney ketone compound (19.6 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) were added 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%.

[0081] The structure and NMR data of the product 1-(4-chlorophenyl)-3-(1,3-dithian-2-yl)-1H-pyrazole obtained in Example 14 are as follows:

[0082]

[0083] 1-(4-Chlorophenyl)-3-(1,3-dithian-2-yl)-1H-pyrazole 1 H NMR(600MHz, CDCl3)δ7.83(d,J=2.5Hz,1H),7.58–7.54(m,4H),6.57(d,J=2.5Hz,1H),5 .41(s,1H),3.08–3.04(m,2H),3.00–2.96(m,2H),2.20–2.17(m,1H),2.03–1.99(m,1H). 13 CNMR (151MHz, CDCl3) δ152.4,139.1,132.5,127.8,120.8,119.9,107.0,44.3,31.4,25.4.

[0084] Preparation of the product 1-(4-bromophenyl)-3-(1,3-dithian-2-yl)-1H-pyrazole obtained in Example 15:

[0085] 2-Ethynyl-1,3-dithiane (14.4 mg, 0.1 mmol), the corresponding Sydney ketone compound (23.9 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) were added 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 70%.

[0086] The structure and NMR data of the product 1-(4-bromophenyl)-3-(1,3-dithian-2-yl)-1H-pyrazole obtained in Example 15 are as follows:

[0087]

[0088] 1-(4-Bromophenyl)-3-(1,3-dithian-2-yl)-1H-pyrazole 1 H NMR (600MHz, CDCl3) δ7.82(d,J=2.4Hz,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 (151MHz, CDCl3) δ152.4,138.6,132.2,129.6,127.9,120.5,106.9,44.3,31.4,25.4.

[0089] Example 16 Preparation of the product 1-(benzo[d][1,3]dioxol-5-yl)-3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazole:

[0090] 2-(Phenylethynyl)-1,3-dithiane (22 mg, 0.1 mmol), the corresponding Sydney ketone compound (20.6 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) were added 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 57%.

[0091] The structure and NMR data of the product 1-(benzo[d][1,3]dioxol-5-yl)-3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazole obtained in Example 16 are as follows:

[0092]

[0093] 1-(Benzo[d][1,3]dioxol-5-yl)-3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazole 1 HNMR (400MHz, CDCl3) δ7.80 (s, 1H), 7.58–7.50 (m, 2H), 7.45 (t, J = 7.6Hz, 2H), 7.39–7.28 (m, 2H), 7.15 (dd, J = 8.4, 2. 2Hz,1H),6.83(d,J=8.3Hz,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(101MHz, CDCl3)δ149.0,148.5,146.5,134.9,132.2,129.0,128.6,127.3,125.6,122.4,112.7,108.3,102.1,101.9,42.5,31.6,25.5.

[0094] 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:

[0095] 2-(Phenylethynyl)-1,3-dithiane (22 mg, 0.1 mmol), the corresponding Sydney ketone compound (24.2 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) were added 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 62%.

[0096] The structure and NMR data of the product 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazole obtained in Example 17 are as follows:

[0097]

[0098] 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazole 1 H NMR(400MHz, CDCl3)δ7.84(s,1H),7.58(d,J=2.2Hz,1H),7.57–7.50(m,2H),7.49–7.43(m,2H) ,7.43–7.33(m,2H),7.10(d,J=8.7Hz,1H),5.29(s,1H),3.12–2.94(m,4H),2.24–2.02(m,2H). 13 C NMR (101MHz, CDCl3) δ149.8, 144.4, 142.3, 136.3, 131.8, 131.6 (t, J = 254.8Hz), 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 (377MHz, CDCl3) δ-49.8

[0099] Preparation of the product obtained in Example 18: 1-(4-bromobiphenyl)-3-(1,3-dithian-2-yl)-4-(6-methoxynaphthalen-2-yl)-1H-pyrazole:

[0100] 2-((6-methoxynaphthalen-2-yl)ethynyl)-1,3-dithiane (30 mg, 0.1 mmol), the corresponding Sydney ketone compound (23.9 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) were added 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 71%.

[0101] The structure and NMR data of the product 1-(4-bromobiphenyl)-3-(1,3-dithian-2-yl)-4-(6-methoxynaphthalen-2-yl)-1H-pyrazole obtained in Example 18 are as follows:

[0102]

[0103] 1-(4-bromobiphenyl)-3-(1,3-dithian-2-yl)-4-(6-methoxynaphthalen-2-yl)-1H-pyrazole 1HNMR(400MHz, CDCl3)δ7.93(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 (101MHz, CDCl3) δ158.0,149.9,138.8,133.8,132.4,129.6,129.1,127.4,127. 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.

[0104] Preparation of the product obtained in Example 19: 3-(1,3-dithian-2-yl)-4-(4-fluorophenyl)-1-phenyl-1H-pyrazole:

[0105] 2-((4-fluorophenyl)ethynyl)-1,3-dithiane (23.8 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 to a dry dimethyl sulfoxide (2 ml) solution. 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 × 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 71%.

[0106] The structure and NMR data of the product 3-(1,3-dithian-2-yl)-4-(4-fluorophenyl)-1-phenyl-1H-pyrazole obtained in Example 19 are as follows:

[0107]

[0108] 3-(1,3-Dithian-2-yl)-4-(4-fluorophenyl)-1-phenyl-1H-pyrazole 1 H NMR(400MHz, CDCl3)δ7.89(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 CNMR(101MHz, CDCl3)δ162.3(d,J=246.7Hz),149.3,139.8,130.3(d,J=8.0Hz),129.5, 128.2(d,J=3.4Hz),126.8,125.4,121.8,119.4,115.9(d,J=21.4Hz),42.5,31.6,25.5. 19 F NMR (377MHz,CDCl3)δ-114.9.

[0109] Preparation of the product obtained in Example 20: 3-(1,3-dithiane-2-yl)-4-(4-chlorophenyl)-1-phenyl-1H-pyrazole:

[0110] 2-((4-chlorophenyl)ethynyl)-1,3-dithiane (25.3 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 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 73%.

[0111] The structure and NMR data of the product 3-(1,3-dithian-2-yl)-4-(4-chlorophenyl)-1-phenyl-1H-pyrazole obtained in Example 20 are as follows:

[0112]

[0113] 3-(1,3-Dithian-2-yl)-4-(4-chlorophenyl)-1-phenyl-1H-pyrazole 1 H NMR(400MHz, CDCl3)δ7.91(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 (101MHz, CDCl3) δ149.2,139.7,133.4,130.7,129.9,129.5,129.2,126.9,125.5,121.6,119.4,42.6,31.6,25.5.

[0114] Preparation of the product obtained in Example 21: 3-(1,3-dithian-2-yl)-4-(4-trifluoromethoxyphenyl)-1-phenyl-1H-pyrazole:

[0115] 2-((4-trifluoromethoxyphenyl)ethynyl)-1,3-dithiane (30.4 mg, 0.1 mmol), phenyl syringone (16.3 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) were added to a dry dimethyl sulfoxide (2 ml) solution. 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 × 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 69%.

[0116] The structure and NMR data of the product 3-(1,3-dithian-2-yl)-4-(4-trifluoromethoxyphenyl)-1-phenyl-1H-pyrazole obtained in Example 21 are as follows:

[0117]

[0118] 3-(1,3-Dithian-2-yl)-4-(4-trifluoromethoxyphenyl)-1-phenyl-1H-pyrazole 1 H NMR(400MHz, CDCl3)δ7.92(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 (101MHz, CDCl3) δ149.2, 148.6, 139.7, 131.0, 130.0, 129.5, 127.0, 125.6, 121.5, 121.4, 120.66 (d, J = 257.1Hz), 119.4, 42.5, 31.6, 25.4. 19 FNMR (377MHz,CDCl3)δ-57.8.

[0119] Preparation of the product obtained in Example 22: 3-(1,3-dithian-2-yl)-4-(4-methoxyphenyl)-1-phenyl-1H-pyrazole:

[0120] 2-((4-methoxyphenyl)ethynyl)-1,3-dithiane (25 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 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 64%.

[0121] The structure and NMR data of the product 3-(1,3-dithian-2-yl)-4-(4-methoxyphenyl)-1-phenyl-1H-pyrazole obtained in Example 22 are as follows:

[0122]

[0123] 3-(1,3-Dithian-2-yl)-4-(4-methoxyphenyl)-1-phenyl-1H-pyrazole 1 H NMR(400MHz, CDCl3)δ7.87(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 (101MHz, CDCl3) δ159.0,149.3,139.9,129.8,129.4,126.6,125.0,124.5,122.3,119.3,114.4,55.4,42.5,31.5,25.5.

[0124] Preparation of the product obtained in Example 23: 3-(1,3-dithian-2-yl)-4-(3-methoxyphenyl)-1-phenyl-1H-pyrazole:

[0125] 2-((3-methoxyphenyl)ethynyl)-1,3-dithiane (25 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 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 64%.

[0126] The structure and NMR data of the product 3-(1,3-dithian-2-yl)-4-(3-methoxyphenyl)-1-phenyl-1H-pyrazole obtained in Example 23 are as follows:

[0127]

[0128] 3-(1,3-Dithian-2-yl)-4-(3-methoxyphenyl)-1-phenyl-1H-pyrazole 1 H NMR(400MHz, CDCl3)δ7.93(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 (101MHz, CDCl3) δ160.0,149.3,139.8,133.5,130.0,129.4,126.8,125.4,122.6,120.9,119.4,113.9,113.2,55.4,42.6,31.6,25.5.

[0129] Preparation of the product obtained in Example 24: 4-(4-(benzyloxy)-3-methoxyphenyl)-3-(1,3-dithian-2-yl)-1-phenyl-1H-pyrazole:

[0130] 2-((4-(Benzyloxy)-3-methoxyphenyl)ethynyl)-1,3-dithiane (35.6 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 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 70%.

[0131] The structure and NMR data of the product 4-(4-(benzyloxy)-3-methoxyphenyl)-3-(1,3-dithian-2-yl)-1-phenyl-1H-pyrazole obtained in Example 24 are as follows:

[0132]

[0133] 4-(4-(Benzyloxy)-3-methoxyphenyl)-3-(1,3-dithian-2-yl)-1-phenyl-1H-pyrazole 1 H NMR (400MHz, CDCl3) δ7.87(s,1H),7.77–7.71(m,2H),7.47(d,J=7.0Hz,2H),7.40(dd,J=16.2,7.8Hz,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 (101MHz, CDCl3) δ149.9,149.3,147.6,139.9,137.2,129.4,128.7,128.0,127.4, 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.

[0134] Preparation of the product obtained in Example 25: 3-(1,3-dithian-2-yl)-1-phenyl-4-(2,4,5-trimethoxyphenyl)-1H-pyrazole:

[0135] 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) were added 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 72%.

[0136] The structure and NMR data of the product 3-(1,3-dithian-2-yl)-1-phenyl-4-(2,4,5-trimethoxyphenyl)-1H-pyrazole obtained in Example 25 are as follows:

[0137]

[0138] 3-(1,3-Dithian-2-yl)-1-phenyl-4-(2,4,5-trimethoxyphenyl)-1H-pyrazole 1 H NMR(400MHz, CDCl3)δ8.00(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 (101MHz, CDCl3) δ151.1,150.4,149.0,143.3,140.0,129.3,126.9,12 6.5,119.3,117.4,114.5,112.4,98.3,56.7,56.6,56.3,42.6,31.3,25.6.

[0139] Preparation of the product obtained in Example 26: 4-(benzofuran-5-yl)-3-(1,3-dithian-2-yl)-1-phenyl-1H-pyrazole:

[0140] 5-((1,3-dithio-2-yl)ethynyl)benzofuran (26 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 to a dry dimethyl sulfoxide (2 ml) solution. 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 × 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 61%.

[0141] The structure and NMR data of the product 4-(benzofuran-5-yl)-3-(1,3-dithian-2-yl)-1-phenyl-1H-pyrazole obtained in Example 26 are as follows:

[0142]

[0143] 4-(Benzofuran-5-yl)-3-(1,3-dithian-2-yl)-1-phenyl-1H-pyrazole 1 H NMR(400MHz, CDCl3)δ7.93(s,1H),7.80–7.74(m,3H),7.68(d,J=2.2Hz,1H),7.58(d,J=8.5Hz,1H),7.50–7.41(m,3H), 7.32–7.27(m,1H),6.83(dd,J=2.2,0.9Hz,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 (101MHz, CDCl3) δ154.5,149.5,145.8,139.9,129.4,128.1,126.9,126.7,125 .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.

[0144] Preparation of the product obtained in Example 27: 3-(1,3-dithian-2-yl)-1-phenyl-4-(thiophen-2-yl)-1H-pyrazole:

[0145] 2-(Thiophene-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) were added 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 70%.

[0146] The structure and NMR data of the product 3-(1,3-dithian-2-yl)-1-phenyl-4-(thiophen-2-yl)-1H-pyrazole obtained in Example 27 are as follows:

[0147]

[0148] 3-(1,3-dithian-2-yl)-1-phenyl-4-(thiophen-2-yl)-1H-pyrazole 1 H NMR(400MHz, CDCl3)δ7.98(s,1H),7.74(dd,J=7.7,1.6Hz,2H),7.44(t,J=7.9Hz,2H),7.33–7.26(m,3 H),7.12(dd,J=5.1,3.5Hz,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 (101MHz, CDCl3) δ149.3,139.6,133.1,129.5,128.0,126.9,125.7,125.6,125.0,119.4,115.8,42.4,31.3,25.6.

[0149] Preparation of the product obtained in Example 28: 3-(1,3-dithiane-2-yl)-4-(6-methoxynaphthalen-2-yl)-1-phenyl-1H-pyrazole:

[0150] 2-((6-methoxynaphthalen-2-yl)ethynyl)-1,3-dithiane (30 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 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%.

[0151] The structure and NMR data of the product 3-(1,3-dithiane-2-yl)-4-(6-methoxynaphthalen-2-yl)-1-phenyl-1H-pyrazole obtained in Example 28 are as follows:

[0152]

[0153] 3-(1,3-dithian-2-yl)-4-(6-methoxynaphthalen-2-yl)-1-phenyl-1H-pyrazole 1 H NMR (400MHz, CDCl3) δ8.00(s,1H),7.96(d,J=1.7Hz,1H),7.84–7.80(m,2H),7.80–7.77(m,2H),7.64(dd,J=8.3,1.8Hz,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 (101MHz, CDCl3) δ158.0,149.6,139.9,133.8,129.7,129.4,129.2,127.5,127. 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.

[0154] Preparation of the product 3-(1,3-dithian-2-yl)-1-phenyl-1H-pyrazole obtained in Example 29:

[0155] 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 to a dry dimethyl sulfoxide (2 ml) solution. 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 × 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%.

[0156] 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:

[0157]

[0158] 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.

[0159] Preparation of the product 3-(1,3-dithian-2-yl)-4-methyl-1-phenyl-1H-pyrazole obtained in Example 30:

[0160] 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 to a dry dimethyl sulfoxide (2 ml) solution. 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 × 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 71%.

[0161] The structure and NMR data of the product 3-(1,3-dithian-2-yl)-4-methyl-1-phenyl-1H-pyrazole obtained in Example 30 are as follows:

[0162]

[0163] 3-(1,3-Dithian-2-yl)-4-methyl-1-phenyl-1H-pyrazole 1 H NMR (400MHz, CDCl3) δ7.67–7.62(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 (101MHz, CDCl3) δ150.1,140.0,129.3,126.6,126.1,118.9,116.5,43.5,31.4,25.6,8.9.

[0164] Preparation of the product 1-(4-chlorophenyl)-3-(1,3-dithian-2-yl)-4-methyl-1H-pyrazole obtained in Example 31:

[0165] 2-(Propan-1-yn-1-yl)-1,3-dithiane (15.8 mg, 0.1 mmol), the corresponding Sydney ketone compound (19.6 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) were added 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 73%.

[0166] The structure and NMR data of the product 1-(4-chlorophenyl)-3-(1,3-dithian-2-yl)-4-methyl-1H-pyrazole obtained in Example 31 are as follows:

[0167]

[0168] 1-(4-Chlorophenyl)-3-(1,3-dithian-2-yl)-4-methyl-1H-pyrazole 1H NMR (400MHz, CDCl3) δ7.63–7.55(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 (101MHz, CDCl3) δ150.5,138.6,131.5,129.4,126.5,120.0,116.9,43.4,31.4,25.5,8.8

[0169] Preparation of the product obtained in Example 32: 1-(4-bromophenyl)-3-(1,3-dithian-2-yl)-4-methyl-1H-pyrazole:

[0170] 2-(Propan-1-yn-1-yl)-1,3-dithiane (15.8 mg, 0.1 mmol), the corresponding Sydney ketone compound (23.9 mg, 0.1 mmol) and potassium tert-butoxide (22.4 mg, 0.2 mmol) were added 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 70%.

[0171] The structure and NMR data of the product 1-(4-bromophenyl)-3-(1,3-dithian-2-yl)-4-methyl-1H-pyrazole obtained in Example 32 are as follows:

[0172]

[0173] 1-(4-Bromophenyl)-3-(1,3-dithian-2-yl)-4-methyl-1H-pyrazole 1 H NMR(400MHz, CDCl3)δ7.61(d,J=1.0Hz,1H),7.56–7.52(m,2H),7.52–7.49(m,2H), 5.34(s,1H),3.06–3.00(m,4H),2.21(s,3H),2.20–2.14(m,1H),2.09–1.99(m,1H). 13 CNMR (101MHz, CDCl3) δ150.6,139.0,132.4,126.5,120.3,119.3,117.0,43.4,31.4,25.5,8.8.

[0174] Preparation of the product obtained in Example 33: 3-(1,3-dithian-2-yl)-4-ethyl-1-phenyl-1H-pyrazole:

[0175] 2-(But-1-yn-1-yl)-1,3-dithiane (17.2 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 to a dry dimethyl sulfoxide (2 ml) solution. 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 × 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 67%.

[0176] The structure and NMR data of the product 3-(1,3-dithian-2-yl)-4-ethyl-1-phenyl-1H-pyrazole obtained in Example 33 are as follows:

[0177]

[0178] 3-(1,3-Dithian-2-yl)-4-ethyl-1-phenyl-1H-pyrazole 1 H NMR (400MHz, CDCl3) δ7.69–7.63(m,3H),7.43–7.36(m,2H),7.25–7.19(m,1H),5.35(s,1H),3 .05–3.00(m,4H),2.69–2.62(m,2H),2.20–2.13(m,1H),2.10–1.99(m,1H),1.30–1.24(m,3H). 13 C NMR (101MHz, CDCl3) δ149.5,140.0,129.3,126.1,125.4,123.5,118.9,43.5,31.5,25.5,17.1,14.8.

[0179] Preparation of the product obtained in Example 34: 3-(1,3-dithian-2-yl)-4-pentyl-1-phenyl-1H-pyrazole:

[0180] 2-(Hept-1-yn-1-yl)-1,3-dithiane (21.4 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 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%.

[0181] The structure and NMR data of the product 3-(1,3-dithian-2-yl)-4-pentyl-1-phenyl-1H-pyrazole obtained in Example 34 are as follows:

[0182]

[0183] 3-(1,3-Dithian-2-yl)-4-pentyl-1-phenyl-1H-pyrazole 1 H NMR (400MHz, CDCl3) δ7.70–7.62(m,3H),7.39(t,J=7.9Hz,2H),7.22(t,J=7.4Hz,1H),5.33(s,1H),3.03(dd,J=7.3,4.0H z,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 (101MHz, CDCl3) δ149.8,140.1,129.3,126.1,125.7,121.9,118.9,43.4,31.7,31.5,30.1,25.6,23.7,22.6,14.2

[0184] Preparation of the product obtained in Example 35: 3-(bis(ethylthio)methyl)-1,4-diphenyl-1H-pyrazole:

[0185] (3-phenylprop-2-yn-1,1-diyl)bis(ethylsulfane) (23.6 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 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 69%.

[0186] The structure and NMR data of the product 3-(bis(ethylthio)methyl)-1,4-diphenyl-1H-pyrazole obtained in Example 35 are as follows:

[0187]

[0188] 3-(Bis(ethylthio)methyl)-1,4-diphenyl-1H-pyrazole 1 H NMR(400MHz, CDCl3)δ7.92(s,1H),7.76–7.68(m,2H),7.59–7.52(m,2H),7.48–7.4 1(m,4H),7.37–7.27(m,2H),5.20(s,1H),2.91–2.68(m,4H),1.23(t,J=7.4Hz,6H). 13 C NMR (101MHz, CDCl3) δ150.4,140.0,132.4,129.5,129.0,128.8,127.3,126.6,125.6,122.4,119.2,45.3,25.4,14.3.

[0189] Preparation of the product 1-(4-bromo-3-chlorophenyl)-4-phenyl-1H-pyrazole-3-carbaldehyde obtained in Example 36:

[0190] 1-(4-bromo-3-chlorophenyl)-3-(1,3-dithian-2-yl)-4-phenyl-1H-pyrazole (45 mg, 0.1 mmol) was dissolved in acetonitrile / water = 5:1 (6 ml). [Bis(trifluoroacetyloxy)iodo]benzene (86 mg, 0.2 mmol) was added to this solution. The resulting mixture was vigorously stirred at 0°C (using an ice bath) until TLC analysis confirmed the disappearance of 1-(4-bromo-3-chlorophenyl)-3-(1,3-disulfanyl-2-yl)-4-phenyl-1H-pyrazole. The mixture was quenched with 1M sodium bicarbonate solution (5 ml), then extracted with dichloromethane (15 ml x 3), and 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 65%.

[0191] 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:

[0192]

[0193] 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

[0194] Preparation of the product 3-methyl-1,4-diphenyl-1H-pyrazole obtained in Example 37:

[0195] 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, extracted with dichloromethane (15 mL×3), and 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%.

[0196] The structure and NMR data of the product 3-methyl-1,4-diphenyl-1H-pyrazole obtained in Example 37 are as follows:

[0197]

[0198] 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 (101MHz, CDCl3) δ148.1,140.1,133.2,129.6,128.8,127.8,126.7,126.2,125.3,123.5,118.9,13.5

[0199] Preparation of the product 3-(difluoromethyl)-1,4-diphenyl-1H-pyrazole obtained in Example 38:

[0200] In a 15 ml centrifuge tube, a suspension of N-iodosuccinimide (NIS) (2 equal parts) in 0.5 ml of dichloromethane was cooled to -78°C and stirred for 10 minutes. Pyridine hydrofluoride (4 equal parts) was added dropwise to the mixture and stirred at -78°C for 5 minutes. Then, a solution of 3-(1,3-dithian-2-yl)-1,4-diphenyl-1H-pyrazole in 0.5 ml of dichloromethane was added dropwise. After the reaction was determined to be complete by TLC, the mixture was heated to ambient temperature, quenched by adding saturated sodium bicarbonate solution (5 ml), and the mixture was stirred for 10 minutes until no 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 obtain the product in a yield of 50%.

[0201] The structure and NMR data of the product 3-(difluoromethyl)-1,4-diphenyl-1H-pyrazole obtained in Example 38 are as follows:

[0202]

[0203] 3-(Difluoromethyl)-1,4-diphenyl-1H-pyrazole 1 H NMR(400MHz, CDCl3)δ8.05(s,1H),7.77–7.70(m,2H),7.60–7.55(m,2H),7.50( t,J=8.0Hz,2H),7.47–7.41(m,2H),7.40–7.33(m,2H),6.86(t,J=54.0Hz,1H). 13 C NMR (101MHz, CDCl3) δ144.3 (t, J = 27.8Hz), 139.5, 130.9, 129.8, 128.9, 128.5 (d, J = 3.9Hz), 127.8, 127.6, 126.9, 123.9, 119.6, 112.0 (t, J = 234.5Hz). 19 F NMR (377MHz, CDCl3) δ-110.22,-110.36.

[0204] Preparation of the product obtained in Example 39: 3-((1-(3,5-dichlorophenyl)-4-phenyl-1H-pyrazol-3-yl)methyl)-1H-indole:

[0205] To a magnetically stirred solution of 1-(3,5-dichlorophenyl)-3-(1,3-dithio-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 vigorously stirred at room temperature for 12 hours and the reaction was complete by TLC detection. 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 obtain the pure desired product in a yield of 58%.

[0206] The structure and NMR data of the product 3-((1-(3,5-dichlorophenyl)-4-phenyl-1H-pyrazol-3-yl)methyl)-1H-indole obtained in Example 39 are as follows:

[0207]

[0208] 3-((1-(3,5-dichlorophenyl)-4-phenyl-1H-pyrazol-3-yl)methyl)-1H-indole 1 H NMR(400MHz, CDCl3)δ8.38(bis,1H),8.12–8.03(m,2H),7.76(dd,J=8.1,1.4Hz ,1H),7.73–7.64(m,1H),7.54–7.48(m,2H),7.45(d,J=8.0Hz,1H),7.33–7.27( m,1H),7.20–7.14(m,1H),7.13(d,J=2.5Hz,1H),6.92–6.85(m,1H),6.57(dd,J =8.0,1.3Hz,1H),6.42–6.33(m,1H),6.19(dd,J=7.6,1.6Hz,1H),4.27(s,2H). 13 C NMR (101MHz, CDCl3) δ160.9,146.6,146.6,138.7,136.1,130.7,129.3,128.7,12 7.5,126.3,124.4,124.0,122.8,120.7,119.7,117.7,116.0,115.3,111.6,40.0.

[0209] Preparation of the product 2-(1-(3,5-dichlorophenyl)-4-phenyl-1H-pyrazol-3-yl)-1,3-dithiane 1,1,3,3-tetraoxide obtained in Example 40:

[0210] 1-(3,5-dichlorophenyl)-3-(1,3-dithio-2-yl)-4-phenyl-1H-pyrazole (40 mg, 0.1 mmol) was dissolved in dichloroethane (4 ml), m-chloroperbenzoic acid (m-CPBA) (103 mg, 0.6 mmol) was dissolved in dichloroethane (4 ml), and then the m-CPBA solution was added to 1-(3,5-dichlorophenyl)-3-(1,3-dithio-2-yl)-4-phenyl-1H-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 obtain the pure desired product in a yield of 67%.

[0211] The structure and NMR data of the product 2-(1-(3,5-dichlorophenyl)-4-phenyl-1H-pyrazol-3-yl)-1,3-dithiane 1,1,3,3-tetraoxide obtained in Example 40 are as follows:

[0212]

[0213] 2-(1-(3,5-dichlorophenyl)-4-phenyl-1H-pyrazol-3-yl)-1,3-dithiane 1,1,3,3-tetraoxide 1 HNMR(400MHz,DMSO)δ9.07(s,1H),8.14(d,J=1.8Hz,2H),7.68(s,1H),7.65–7.5 3(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 (101MHz, DMSO) δ141.0,135.7,130.4,129.6,129.2,129.0,128.6,128.5,127.1,117.8,78.3,50.0,18.1.

Claims

1. The present invention relates to a 1,3-dithiane-substituted pyrazole derivative and a preparation method and application thereof, characterized in that: The 1,3-dithiane-substituted pyrazole derivative has the following structure (I): In structure (Ⅰ), R 1 is an aliphatic substituent (the substituent is selected from hydrogen, methyl, ethyl, etc.), a substituted phenyl (the substituent is selected from one or more of hydrogen, methoxy, fluorine, chlorine, trifluoromethoxy), naphthyl, benzofuranyl, thienyl, etc.; R 2 It is a substituted phenyl group (the substituent is selected from one or more of hydrogen, methoxy, fluorine, chlorine, bromine and trifluoromethoxy), or a benzodioxolane group.

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

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

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 1,3-dithiane-substituted pyrazole derivative (I) into a reaction container, and reacting at -78°C to obtain the target product VI.

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

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