Deuterated methyl heteroaryl sulfone compound as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of organic synthesis, and provides a deuterated methyl heteroaryl sulfone compound as well as a preparation method and application thereof. Specifically, the deuterated methyl heteroaryl sulfone compound disclosed by the invention has a structure as shown in a formula I in the specification. Moreover, the preparation method overcomes the adverse conditions that the reaction conditions are harsh, a large number of deuterium sources need to be used and the like in the prior art, and is more efficient, green and convenient. Besides, the deuterated methyl heteroaryl sulfone compound can be applied to introduction of a CD3SO2 group into various substrates, only one equivalent amount of the deuterated methyl heteroaryl sulfone compound can be used, and the deuterated methyl heteroaryl sulfone compound is wide in application prospect. # imgabs0 #

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis and relates to a deuterated methyl heteroaryl sulfone compound and a preparation method and application thereof. Background Art

[0002] Deuterium, an isotope of hydrogen, 2 H or D) plays a very important role in many fields. Since the bond length of CD is shorter than that of CH and the resonance frequency is lower, deuterated compounds have important applications in the mechanism verification of organic synthesis and the analysis and detection of compounds (for example, various deuterated solvents in nuclear magnetic resonance testing, or deuterated markers for in vivo drug testing). In addition, deuterium also has the characteristics of smaller molar volume, lower lipophilicity and larger atomic mass, which can improve the absorption, distribution, metabolism and excretion of some drug molecules in the human body, thereby improving the efficacy, tolerability and safety of these drugs.

[0003] In the past few decades, a variety of deuterated drug candidates have entered the clinical trial stage. In 2017, the FDA approved the first deuterated drug, Antetanin (deuterated tetrabenazine), for the treatment of Huntington's disease and tardive dyskinesia. The active metabolites of tetrabenazine are metabolized quickly in the body, resulting in an increased frequency of medication, while the half-life of the drug after deuteration is prolonged, overcoming the problem of frequent medication.

[0004]

[0005] The methyl sulfone structure is commonly found in natural products and drugs. As a polar group, it can not only improve the physical and chemical properties of the compound, but also participate in the pharmacokinetic process of the drug in the body, playing a vital role in biological activity. For example, firocoxib is an important non-steroidal anti-inflammatory drug, and vismodegib is a drug for the treatment of basal cell carcinoma. They both have a methyl sulfone structure, which plays an important role in the binding of the drug to the target, and making it into a corresponding deuterated compound may further improve the performance of the drug.

[0006]

[0007] Deuterated methylsulfonyl is a group with certain drug-making potential, but in the prior art, the traditional method of constructing deuterated methyl sulfone fragments in drug structures is mainly through direct synthesis from sulfinates and halogenated hydrocarbons. The disadvantage of this method is that the source of sulfinates is limited, and it is not practical for the synthesis of complex sulfone compounds.

[0008] CN107827688A discloses a method of using deuterated DMSO as a deuterium source, introducing deuterated methylthio groups, and then obtaining deuterated methyl sulfone by oxidation. However, this method requires the use of a large amount of deuterated reagents as substrates or solvents, and is synthesized through multiple steps, which is costly and limits its application on an industrial scale.

[0009]

[0010] Reference 1 [1] The invention discloses a method of preparing a deuterated methyl sulfide compound by using thiourea, aliphatic halogenated hydrocarbon and CD3I, and then oxidizing the compound with hydrogen peroxide to obtain a deuterated methyl sulfone compound.

[0011]

[0012] Reference 2 [2] The invention discloses using deuterated methanol as a deuterium source, preparing TsSCD3 through a two-step reaction, and using it as a deuterated methylthio source to realize a direct deuterated methylthioation reaction of a nucleophilic / electrophilic reagent, and then oxidizing it to prepare a deuterated methyl sulfone compound. The method has many steps and uses a nickel catalyst, a metal reagent such as Zn, and has a high cost.

[0013]

[0014] In view of the importance of deuterated compounds, it is necessary to develop a practical and versatile deuterated methyl sulfone reagent and a preparation method thereof. In addition, it is particularly important to explore a method for introducing a deuterated methyl sulfone group into a suitable substrate using the deuterated methyl sulfone reagent (especially a method for synthesizing a target product from 1 equivalent of the deuterated methyl sulfone reagent).

[0015] [1]Reisenauer HP,Schreiner PR,Romański J.,Mlostoń,G.Gas-PhaseGeneration and Matrix Isolation of the Methylsulfonyl Radical CH3SO2·fromAllylmethylsulfone[J].The Journal of Physical Chemistry A, 2015,119(11):2211-2216.

[0016] [2] Yan Z, Wen L, Yuenian Summary of the invention

[0017] Problem that the invention aims to solve

[0018] The present invention provides a deuterated methyl heteroaryl sulfone compound and a preparation method and use thereof, so as to solve the technical problems existing in the prior art such as harsh reaction conditions, the need to use a large amount of deuterium source, complex operation process, and unsuitability for industrial production.

[0019] Solutions for solving problems

[0020] In a first aspect, the present invention provides a compound having formula I,

[0021]

[0022] in:

[0023] R1, R2, R3 and R4 are each independently hydrogen, C1-C6 alkyl, deuterated C1-C6 alkyl, C1-C6 alkanoyl, C1-C6 alkanoyloxy, C1-C6 alkoxycarbonyl or C6-C 12 Aryl; preferably, R1, R2, R3 and R4 are each independently hydrogen, C1-C3 alkyl, deuterated C1-C3 alkyl, C1-C3 alkanoyl, C1-C3 alkanoyloxy, C1-C3 alkoxycarbonyl or phenyl; more preferably, R1, R2, R3 and R4 are each independently hydrogen or C1-C3 alkyl; further preferably, R1, R2, R3 and R4 are each independently hydrogen or methyl;

[0024] A is S or O; preferably, A is S.

[0025] Preferably, the compound is selected from the following compounds:

[0026]

[0027] More preferably, the compound is selected from the following compounds:

[0028]

[0029] In a second aspect, the present invention provides a method for preparing the above compound, comprising the following steps:

[0030] (1) Under the protection of an inert gas, compound II reacts with a deuterated methylation reagent to obtain compound III.

[0031]

[0032] (2) Compound III reacts with an oxidant to obtain Compound I,

[0033]

[0034] wherein A, R1, R2, R3 and R4 are as defined in Formula I.

[0035] Preferably, in step (1), the deuterated methylation agent is at least one of deuterated iodomethane (iodomethane-D3), deuterated dimethyl sulfate (dimethyl sulfate-D6) and deuterated methyl trifluoromethanesulfonate (methyl trifluoromethanesulfonate-D3), preferably deuterated iodomethane.

[0036] Preferably, in step (1), the molar ratio of the compound II to the deuterated methylation agent is 1:1 to 1:3, preferably 1:1.2.

[0037] Preferably, in step (1), the reaction is carried out in the presence of a base.

[0038] More preferably, the base is an inorganic base, preferably at least one of potassium carbonate, sodium carbonate, potassium hydroxide and sodium hydroxide, more preferably potassium carbonate.

[0039] Preferably, in step (1), the molar ratio of the compound II to the base is 1:1.2 to 1:5, preferably 1:1.2.

[0040] Preferably, in step (1), the inert gas is nitrogen.

[0041] Preferably, in step (1), the reaction is carried out in a polar aprotic solvent.

[0042] More preferably, the polar aprotic solvent is at least one of N,N-dimethylformamide, 1,4-dioxane, tetrahydrofuran and acetonitrile, preferably N,N-dimethylformamide.

[0043] Preferably, the usage ratio of the compound II to the polar aprotic solvent is 1 g:10 mL to 1 g:40 mL, preferably 1 g:20 mL.

[0044] Preferably, in step (1), the reaction temperature is 0°C to 25°C, preferably 25°C.

[0045] Preferably, in step (1), the reaction time is 4 h to 12 h, preferably 12 h.

[0046] Preferably, in step (2), the oxidant is at least one of hydrogen peroxide or its aqueous solution and m-chloroperbenzoic acid, preferably an aqueous hydrogen peroxide solution, and more preferably an aqueous hydrogen peroxide solution with a mass fraction of 30%.

[0047] Preferably, the molar ratio of the compound III to the oxidant is 1:3 to 1:20, preferably 1:10, calculated as hydrogen peroxide or meta-chloroperbenzoic acid.

[0048] Preferably, in step (2), the reaction is carried out in the presence of a catalyst.

[0049] More preferably, the catalyst is at least one of ammonium molybdate tetrahydrate, sodium tungstate dihydrate and ethylenediaminetetraacetic acid, preferably ammonium molybdate tetrahydrate.

[0050] Preferably, in step (2), the molar ratio of the compound III to the catalyst is 1:0.01 to 1:0.8, preferably 1:0.1.

[0051] Preferably, in step (2), the reaction is carried out in a polar organic solvent.

[0052] More preferably, the polar organic solvent is at least one of alcohols and nitriles, preferably alcohols, more preferably at least one of methanol and ethanol, further preferably ethanol.

[0053] Preferably, in step (2), the usage ratio of the compound III to the polar organic solvent is 1 g:10 mL to 1 g:40 mL, preferably 1 g:20 mL.

[0054] Preferably, in step (2), the reaction temperature is 0°C to 25°C, preferably 25°C.

[0055] Preferably, in step (2), the reaction time is 8 h to 16 h, preferably 12 h.

[0056] In a third aspect, the present invention provides a use of the above-mentioned compound (especially the compound described in the first aspect of the present invention) in the deuterated mesylation reaction of a substrate.

[0057] Preferably, in the deuterated mesylation reaction, the compound is used as a deuterated mesylate donor reagent.

[0058] Preferably, the substrate contains a leaving group.

[0059] More preferably, the leaving group is halogen, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy, preferably halogen, more preferably bromine.

[0060] In a fourth aspect, the present invention provides a method for introducing a deuterated methylsulfonyl group into a substrate, comprising the following steps:

[0061] (1) The compound described in the first aspect of the present invention and p-toluene thiophenol react in a polar aprotic solvent under the action of a base to obtain a reaction solution;

[0062] (2) adding the substrate to the reaction solution of step (1) to carry out a reaction to obtain a deuterated methylsulfonyl-substituted substrate.

[0063] Preferably, in step (1), the base is at least one of potassium carbonate, sodium carbonate, potassium hydroxide and sodium hydroxide, preferably potassium carbonate.

[0064] Preferably, in step (1), the polar aprotic solvent is at least one of N,N-dimethylformamide, 1,4-dioxane, tetrahydrofuran and acetonitrile, preferably N,N-dimethylformamide.

[0065] Preferably, in step (1), the reaction time is 2 h to 10 h, preferably 5 h.

[0066] Preferably, in step (1), the reaction temperature is room temperature.

[0067] Preferably, in step (2), the reaction time is 6 h to 18 h, preferably 12 h.

[0068] Preferably, in step (2), the reaction temperature is room temperature.

[0069] Preferably, the substrate contains a leaving group.

[0070] More preferably, the leaving group is halogen, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy, preferably halogen, more preferably bromine.

[0071] Preferably, the substrate in the third aspect and the fourth aspect of the present invention is selected from the following compounds:

[0072]

[0073] Effects of the Invention

[0074] 1. The present invention uses heteroarylthiophenol as a raw material, uses about 1 equivalent of deuterated iodomethane as a deuterium source, activates the heteroarylthiophenol with an alkali to generate a deuterated methyl sulfide intermediate, and finally generates a deuterated methyl heteroaryl sulfone compound under the action of a catalyst and an oxidant. The reaction is carried out at 0° C. to 25° C., which overcomes the unfavorable conditions of the prior art such as harsh reaction conditions and the need to use a large amount of deuterium source, and is more efficient, green and convenient.

[0075] 2. The preparation of the deuterated methyl heteroaryl sulfone compounds of the present invention realizes a gram-scale reaction, is practical, and is suitable for industrial-scale production.

[0076] 3. The reaction of the present invention is efficient, has a high yield, and the preparation method is simple and stable, has no irritating odor, and has mild reaction conditions.

[0077] 4. The deuterated methyl heteroaryl sulfone compounds of the present invention can be used to introduce CD3SO2 groups into various substrates, and only one equivalent amount can be used, so the application prospects are broad. DETAILED DESCRIPTION

[0078] In this specification, the word "may" means both performing a certain process and not performing a certain process.

[0079] In this specification, "comprising", "having", "including" or "containing" may mean inclusive or open-ended, not excluding additional, uncited elements or method steps. At the same time, "comprising", "having", "including" or "containing" may also mean closed, excluding additional, uncited elements or method steps.

[0080] In this specification, the numerical range expressed using "a numerical value A to a numerical value B" means a range including the endpoints numerical values ​​A and B.

[0081] In this specification, unless otherwise specified, the "normal temperature" or "room temperature" used generally refers to the temperature of 25±2°C.

[0082] In this specification, the unit names used are all international standard unit names, and unless otherwise stated, the "%" used indicates weight or mass percentage.

[0083] In this specification, the references to "some specific / preferred embodiments", "other specific / preferred embodiments", "embodiments", etc., mean that the specific elements (e.g., features, structures, properties and / or characteristics) described in connection with the embodiments are included in at least one embodiment described herein, and may or may not exist in other embodiments. In addition, it should be understood that the elements may be combined in various embodiments in any suitable manner.

[0084] Definition of terms

[0085] Unless otherwise specified, the term "each independently" means that at least two groups (or ring systems) with the same or similar value ranges in the structure may have the same or different meanings under certain circumstances. For example, X and Y are each independently hydrogen, halogen, hydroxyl, cyano, alkyl or aryl, then when X is hydrogen, Y can be either hydrogen, or halogen, hydroxyl, cyano, alkyl or aryl; similarly, when Y is hydrogen, X can be either hydrogen, or halogen, hydroxyl, cyano, alkyl or aryl.

[0086] Unless otherwise specified, the term "C1-C6 alkyl" refers to a saturated straight or branched chain alkyl group containing 1 to 6 carbon atoms, either alone or in combination, including but not limited to methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, 2-pentyl, 3-pentyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 3-methyl-1-butyl, 2-methyl-1-butyl, n-hexyl, 2-hexyl, 3-hexyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 3-methyl-3-pentyl, 2-methyl-3-pentyl, 2,3-dimethyl-2-butyl and 3,3-dimethyl-2-butyl. Similarly, the term "C1-C3 alkyl" alone or in combination means a saturated straight or branched chain alkyl group containing 1 to 3 carbon atoms, including methyl, ethyl, propyl, isopropyl, and the like.

[0087] Unless otherwise specified, the term "C1-C6 alkanoyl" refers to a monovalent straight or branched group consisting of carbon atoms (1 to 6), hydrogen atoms and oxygen atoms, containing no unsaturation except for the carbonyl group in its own structure, and connected to the parent nucleus via a single bond to the carbonyl group; common C1-C6 alkanoyl groups include (but are not limited to) formyl (-C(=O)H), acetyl (-C(=O)CH3), n-propionyl (-C(=O)CH2CH3), n-butyryl (-C(=O)CH2CH2CH3), isobutyryl (-C(=O)CH(CH3)2), n-valeryl (-C(=O)CH2CH2CH2CH3), pivaloyl (-C(=O)C(CH3)3), etc.

[0088] Unless otherwise specified, the term "C1-C6 alkanoyloxy" refers to a monovalent straight or branched group consisting solely of carbon atoms (1 to 6), hydrogen atoms, and oxygen atoms, containing no unsaturation except for the carbonyl group in its own structure, and connected to the parent nucleus via a single bond to the oxygen atom; common C1-C6 alkanoyloxy groups include, but are not limited to, formyloxy (-OC(=O)H), acetyloxy (-OC(=O)CH3), n-propionyloxy (-OC(=O)CH2CH3), n-butyryloxy (-OC(=O)CH2CH2CH3), isobutyryloxy (-OC(=O)CH(CH3)2), n-valeryloxy (-OC(=O)CH2CH2CH2CH3), pivaloyloxy (-OC(=O)C(CH3)3), and the like.

[0089] Unless otherwise specified, the term "C1-C6 alkoxycarbonyl" refers to a monovalent straight or branched group consisting solely of carbon atoms (1 to 6), hydrogen atoms and oxygen atoms, containing no unsaturation except for the carbonyl group in its own structure, and connected to the parent nucleus via a single bond to the carbonyl group; common C1-C6 alkoxycarbonyl groups include, but are not limited to, methoxycarbonyl (-C(=O)OCH3), ethoxycarbonyl (-C(=O)OCH2CH3), n-propoxycarbonyl (-C(=O)OCH2CH2CH3), isopropoxycarbonyl (-C(=O)OCH(CH3)2), n-butoxycarbonyl (-C(=O)OCH2CH2CH2CH3), tert-butoxycarbonyl (-C(=O)OC(CH3)3), and the like.

[0090] Unless otherwise specified, the term “C6-C 12 "Aryl" refers to a monovalent monocyclic or polycyclic (including fused forms) aromatic ring system, which consists of only carbon atoms and hydrogen atoms and is connected to the parent nucleus by a single bond; the common C6-C 12 Aryl groups include, but are not limited to, phenyl, naphthyl, and the like.

[0091] Unless otherwise specified, the term "halogen" refers to fluorine (F), chlorine (Cl), bromine (Br) and iodine (I) located in Group VII of the Periodic Table of the Elements.

[0092] Example

[0093] Various exemplary embodiments, features and aspects of the present invention will be described in detail below. The word "exemplary" used here means "used as an example, embodiment or illustrative". Any embodiment described here as "exemplary" is not necessarily interpreted as being superior or better than other embodiments.

[0094] In addition, in order to better illustrate the present invention, numerous specific details are provided in the following specific embodiments. It should be understood by those skilled in the art that the present invention can be implemented without certain specific details. In other examples, methods, means, equipment and steps well known to those skilled in the art are not described in detail in order to highlight the subject matter of the present invention.

[0095] Unless otherwise stated, the units used in this specification are all international standard units, and the numerical values ​​and numerical ranges appearing in the present invention should be understood to include the inevitable systematic errors in industrial production.

[0096] The embodiments of the present invention will be described in detail below in conjunction with the examples, but those skilled in the art will appreciate that the following examples are only used to illustrate the present invention and should not be considered to limit the scope of the present invention. If no specific conditions are specified in the examples, they are carried out according to normal conditions or the conditions recommended by the manufacturer. If the manufacturer is not specified for the reagents or instruments used, they are all conventional products that can be obtained commercially.

[0097] [Preparation of deuterated methyl sulfone reagent]

[0098] Embodiment 1:

[0099]

[0100] Step 1: Under nitrogen protection, add benzo[d]thiazole-2-thiophenol (compound 1a, 10 g, 59.79 mmol, 1 equiv), potassium carbonate (9.9 g, 71.748 mmol, 1.2 equiv) and N,N-dimethylformamide (200 mL) to a round-bottom flask, control the temperature to 0-5 ° C, and then add deuterated iodomethane (10.18 g, 71.748 mmol, 1.2 equiv). After the addition is completed, the reaction is stirred at room temperature overnight. After the reaction is completed, the solution is extracted three times with ethyl acetate and water, the organic phases are combined, and dried over anhydrous sodium sulfate. Let stand for 10 minutes, filter out the organic phase, and remove the organic solvent by vacuum rotary evaporation to obtain a crude compound 2a, which can be used in the next step without purification.

[0101] Step 2: Add crude compound 2a, (NH4)6Mo7O 244H2O (7.4 g, 5.98 mmol, 0.1 equiv) and ethanol (200 mL) were cooled to 0-5°C, and then a hydrogen peroxide solution (30%, based on H2O2, 20.34 g, 598 mmol, 10 equiv) was slowly added under stirring. After the addition was completed, the mixture was warmed to room temperature and stirred for 12 h. After the reaction was completed by TLC detection, the solution was extracted three times with ethyl acetate and water, the organic phases were combined, and dried over anhydrous sodium sulfate. After standing for 10 min, the organic phase was filtered out, the organic solvent was removed by vacuum rotary evaporation, and finally purified by column chromatography (petroleum ether: ethyl acetate = 10: 1, v / v) to obtain compound 3a (9.1 g, yield: 71.25%, deuteration rate> 99%).

[0102] 1 H NMR (400MHz, CDCl3): δ8.16-8.09(m,1H),7.97-7.90(m,1H),7.60-7.47(m,2H).

[0103] MS-ESI: m / z 217 [M+H] + , the measured value is 217.

[0104] Embodiment 2:

[0105]

[0106] Step 1: Under nitrogen protection, add benzo[d]oxazole-2-thiophenol (compound 1b, 10g, 66.15mmol, 1equiv), potassium carbonate (10.97g, 79.37mmol, 1.2equiv) and N,N-dimethylformamide (200mL) to a round-bottom flask, control the temperature to 0-5°C, then add deuterated iodomethane (11.51g, 79.37mmol, 1.2equiv), and after the addition is complete, stir the reaction at room temperature overnight. After the reaction is complete, extract the solution three times with ethyl acetate and water, combine the organic phases, and dry over anhydrous sodium sulfate. Let stand for 10min, filter out the organic phase, and remove the organic solvent by vacuum rotary evaporation to obtain a crude compound 2b, which can be used in the next step without purification.

[0107] Step 2: Add crude compound 2b, (NH4)6Mo7O 244H2O (8.03 g, 6.5 mmol, 0.1 equiv) and ethanol (200 mL) were cooled to 0-5°C, and then, under stirring, a hydrogen peroxide solution (30%, based on H2O2, 22.10 g, 649.71 mmol, 10 equiv) was slowly added. After the addition was complete, the mixture was warmed to room temperature and stirred for 12 h. After the reaction was completed by TLC, the solution was extracted three times with ethyl acetate and water, the organic phases were combined, and dried over anhydrous sodium sulfate. After standing for 10 min, the organic phase was filtered out, the organic solvent was removed by vacuum rotary evaporation, and finally purified by column chromatography (petroleum ether: ethyl acetate = 10: 1, v / v) to obtain compound 3b (10 g, yield: 76.87%, deuteration rate> 99%).

[0108] 1 H NMR (400MHz, CDCl3): δ7.90-7.63(m,2H),7.51-7.23(m,2H).

[0109] MS-ESI: m / z theoretical value 201 [M+H] + , measured value is 201.

[0110] Embodiment 3:

[0111]

[0112] Step 1: Under nitrogen protection, add 6-methylbenzo[d]thiazole-2-thiophenol (compound 1c, 11 g, 60.53 mmol, 1 equiv), potassium carbonate (10.04 g, 72.63 mmol, 1.2 equiv) and N,N-dimethylformamide (200 mL) to a round-bottom flask, control the temperature to 0-5°C, then add deuterated iodomethane (10.53 g, 72.63 mmol, 1.2 equiv), and after the addition is complete, stir the reaction at room temperature overnight. After the reaction is complete, extract the solution three times with ethyl acetate and water, combine the organic phases, and dry over anhydrous sodium sulfate. Let stand for 10 min, filter out the organic phase, and remove the organic solvent by vacuum rotary evaporation to obtain a crude compound 2c, which can be used in the next step without purification.

[0113] Step 2: Add crude compound 2c, (NH4)6Mo7O 244H2O (7.48 g, 6.05 mmol, 0.1 equiv) and ethanol (200 mL) were cooled to 0-5°C, and then, under stirring, a hydrogen peroxide solution (30%, based on H2O2, 20.59 g, 605.2 mmol, 10 equiv) was slowly added. After the addition was complete, the mixture was warmed to room temperature and stirred for 12 h. After the reaction was completed by TLC detection, the solution was extracted three times with ethyl acetate and water, the organic phases were combined, and dried over anhydrous sodium sulfate. After standing for 10 min, the organic phase was filtered out, the organic solvent was removed by vacuum rotary evaporation, and finally purified by column chromatography (petroleum ether: ethyl acetate = 10: 1, v / v) to obtain compound 3c (9 g, yield: 64.64%, deuteration rate> 99%).

[0114] 1 H NMR (500MHz, CDCl3): δ7.90-7.75(m,1H),7.72-7.65(m,1H),7.36-7.30(m,1H),2.44(s,3H).

[0115] MS-ESI: m / z 231[M+H] + , measured value is 231.

[0116] [Application of deuterated methyl sulfone reagent]

[0117] Embodiment 4:

[0118]

[0119] Under nitrogen protection, at room temperature, compound 3a (2 g, 9.25 mmol, 1 equiv) prepared according to the method in Example 1, p-toluene thiophenol (1.38 g, 11.10 mmol, 1.2 equiv) and potassium carbonate (1.53 g, 11.10 mmol, 1.2 equiv) were added to the reaction tube, and N, N-dimethylformamide (20 mL) was added to the above system by syringe. After the addition was completed, the reactants were placed at room temperature for 5 h. After the reaction was completed, compound 5a (3.08 g, 11.10 mmol, 1.2 equiv) was added to the reaction solution, and then placed at room temperature for 12 h. After the reaction was completed, the solution was extracted three times with ethyl acetate and water, and the organic phases were combined and dried over anhydrous sodium sulfate. After standing for 10 min, the organic phase was filtered out, and the organic solvent was removed by rotary evaporation under reduced pressure. Finally, the product was purified by column chromatography (petroleum ether:ethyl acetate=2:1, v / v) to obtain the target product 6a (2.1 g, yield: 81.28%).

[0120] 1H NMR (400MHz, CDCl3): δ4.79(td,J=10.9,4.5Hz,1H),3.95(s,2H),2.02(dtd,J=11.9,4.1,1.8Hz,1H),1.90(pd,J=7.0,2.7Hz,1H),1.69( dt,J=15.0,4.2Hz,2H),1.56-1.37(m,2H),1.13-0.98(m,2H),0.90(t,J=6.6Hz,6H),0.84(dd,J=12.5,3.5Hz,1H),0.75(d,J=7.0Hz,3H).

[0121] IR(neat):2953,2366,2633,1725,1647,1388,1279cm -1 .

[0122] HR-MS (ESI-TOF) m / z: theoretical value 302.1476 [M+Na] + , the measured value is 302.1462.

[0123] Embodiment 5:

[0124]

[0125] Under nitrogen protection, at room temperature, compound 3a (2 g, 9.25 mmol, 1 equiv) prepared according to the method in Example 1, p-toluene thiophenol (1.38 g, 11.10 mmol, 1.2 equiv) and potassium carbonate (1.53 g, 11.10 mmol, 1.2 equiv) were added to the reaction tube, and N,N-dimethylformamide (20 mL) was added to the above system by syringe. After the addition was completed, the reactants were placed at room temperature for 5 h. After the reaction was completed, compound 5b (2.2 g, 11.10 mmol, 1.2 equiv) was added to the reaction solution, and then placed at room temperature for 12 h. After the reaction was completed, the solution was extracted three times with ethyl acetate and water, and the organic phases were combined and dried over anhydrous sodium sulfate. After standing for 10 min, the organic phase was filtered out, and the organic solvent was removed by rotary evaporation under reduced pressure. Finally, the product was purified by column chromatography (petroleum ether:ethyl acetate=2:1, v / v) to obtain the target product 6b (1.67 g, yield: 91%).

[0126] 1 H NMR (400MHz, CDCl3): δ8.03-7.93(m,2H),7.69-7.61(m,1H),7.55-7.47(m,2H),4.61(s,2H).

[0127] IR(neat):3743,2370,2371,1835,1741,1725,1693,1646,1547,1426cm -1 .

[0128] HR-MS (ESI-TOF) m / z: theoretical value 224.0431 [M+Na] + , the measured value is 224.0439.

[0129] Embodiment 6:

[0130]

[0131] Under nitrogen protection, at room temperature, compound 3a (2 g, 9.25 mmol, 1 equiv) prepared according to the method in Example 1, p-toluene thiophenol (1.38 g, 11.10 mmol, 1.2 equiv) and potassium carbonate (1.53 g, 11.10 mmol, 1.2 equiv) were added to the reaction tube, and N,N-dimethylformamide (20 mL) was added to the above system using a syringe. After the addition was completed, the reactants were placed at room temperature for 5 h. After the reaction was completed, compound 5g (2.8 g, 11.10 mmol, 1.2 equiv) was added to the reaction solution, and then placed at room temperature for 12 h. After the reaction was completed, the solution was extracted three times with ethyl acetate and water, and the organic phases were combined and dried over anhydrous sodium sulfate. After standing for 10 min, the organic phase was filtered out, and the organic solvent was removed by rotary evaporation under reduced pressure. Finally, the product was purified by column chromatography (petroleum ether:ethyl acetate=2:1, v / v) to obtain 6 g (1.72 g, yield: 75%) of the target product.

[0132] 1 H NMR (400MHz, CDCl3): δ8.55-8.48(m,1H),8.06-7.96(m,2H),7.95-7.86(m,2H),7.68-7.61(m,1H),7.61-7.53(m,1H),4.73(s,2H).

[0133] IR(neat):3427,2262,2129,1674,1621,1464cm -1 .

[0134] HR-MS (ESI-TOF) m / z: theoretical value 252.0768 [M+H] + , the measured value is 252.0766.

[0135] Embodiment 7:

[0136]

[0137] Under nitrogen protection, at room temperature, compound 3a (2 g, 9.25 mmol, 1 equiv) prepared according to the method in Example 1, p-toluene thiophenol (1.38 g, 11.10 mmol, 1.2 equiv) and potassium carbonate (1.53 g, 11.10 mmol, 1.2 equiv) were added to the reaction tube, and N, N-dimethylformamide (20 mL) was added to the above system by syringe. After the addition was completed, the reactants were placed at room temperature for 5 h. After the reaction was completed, compound 5i (3.04 g, 11.10 mmol, 1.2 equiv) was added to the reaction solution, and then placed at room temperature for 12 h. After the reaction was completed, the solution was extracted three times with ethyl acetate and water, and the organic phases were combined and dried over anhydrous sodium sulfate. After standing for 10 min, the organic phase was filtered out, and the organic solvent was removed by rotary evaporation under reduced pressure. Finally, the product was purified by column chromatography (petroleum ether:ethyl acetate=2:1, v / v) to obtain the target product 6i (1.56 g, yield: 61%).

[0138] 1 H NMR (400MHz, CDCl3): δ7.84 (dt, J=8.1, 0.9Hz, 1H), 7.75 (dt, J=8.0, 0.9Hz, 1H), 7.41 (ddd, J=8. 3,7.3,1.3Hz,1H),7.30(ddd,J=8.3,7.3,1.2Hz,1H),3.53(t,J=6.9Hz,2H),3.27-3.18(m,2H).

[0139] IR(neat):3743,2369,2319,1770,1741,1725,1693,1515cm -1 .

[0140] HR-MS (ESI-TOF) m / z: theoretical value 299.0369 [M+Na] + , the measured value is 299.0377.

[0141] Embodiment 8:

[0142]

[0143] Under nitrogen protection, at room temperature, compound 3a (2 g, 9.25 mmol, 1 equiv) prepared according to the method in Example 1, p-toluene thiophenol (1.38 g, 11.10 mmol, 1.2 equiv) and potassium carbonate (1.53 g, 11.10 mmol, 1.2 equiv) were added to the reaction tube, and N,N-dimethylformamide (20 mL) was added to the above system using a syringe. After the addition was completed, the reactants were placed at room temperature for 5 h. After the reaction was completed, compound 5j (3.20 g, 11.10 mmol, 1.2 equiv) was added to the reaction solution, and then placed at room temperature for 12 h. After the reaction was completed, the solution was extracted three times with ethyl acetate and water, and the organic phases were combined and dried over anhydrous sodium sulfate. After standing for 10 min, the organic phase was filtered out, and the organic solvent was removed by rotary evaporation under reduced pressure. Finally, the product was purified by column chromatography (petroleum ether:ethyl acetate=2:1, v / v) to obtain the target product 6j (2.44 g, yield: 91%).

[0144] 1 H NMR (400MHz, CDCl3): δ7.84 (dt, J=8.1, 0.9Hz, 1H), 7.75 (dt, J=8.0, 0.9Hz, 1H), 7.41 (ddd, J=8.3, 7.3, 1. 3Hz, 1H), 7.30 (ddd, J=8.3, 7.3, 1.2Hz, 1H), 3.53 (t, J=6.9Hz, 2H), 3.27-3.18 (m, 2H), 2.48-2.38 (m, 2H).

[0145] IR(neat):3743,2369,2319,1770,1741,1725,1693,1515cm -1 .

[0146] HR-MS (ESI-TOF) m / z: theoretical value 291.0369 [M+H] + , the measured value is 291.0377.

[0147] Embodiment 9:

[0148]

[0149] Under nitrogen protection, at room temperature, compound 3a (2 g, 9.25 mmol, 1 equiv) prepared according to the method in Example 1, p-toluene thiophenol (1.38 g, 11.10 mmol, 1.2 equiv) and potassium carbonate (1.53 g, 11.10 mmol, 1.2 equiv) were added to the reaction tube, and N,N-dimethylformamide (20 mL) was added to the above system by syringe. After the addition was completed, the reactants were placed at room temperature for 5 h. After the reaction was completed, compound 5n (1.65 g, 11.10 mmol, 1.2 equiv) was added to the reaction solution, and then placed at room temperature for 12 h. After the reaction was completed, the solution was extracted three times with ethyl acetate and water, and the organic phases were combined and dried over anhydrous sodium sulfate. After standing for 10 min, the organic phase was filtered out, and the organic solvent was removed by rotary evaporation under reduced pressure. Finally, the product was purified by column chromatography (petroleum ether:ethyl acetate=2:1, v / v) to obtain the target product 6n (1.3 g, yield: 93%).

[0150] 1 H NMR (400MHz, CDCl3): δ5.83-5.66(m,1H),5.13-5.01(m,2H),3.06-2.94(m,2H),2.22(qt,J=7.1,1.4Hz,2H),2.05-1.88(m,2H).

[0151] IR(neat):2945,2267,2133,1641,1456,1417,1288cm -1 .

[0152] HR-MS (ESI-TOF) m / z: theoretical value 174.0639 [M+Na] + , the measured value is 174.0627.

[0153] Embodiment 10:

[0154]

[0155] Under nitrogen protection, at room temperature, compound 3a (2 g, 9.25 mmol, 1 equiv) prepared according to the method in Example 1, p-toluene thiophenol (1.38 g, 11.10 mmol, 1.2 equiv) and potassium carbonate (1.53 g, 11.10 mmol, 1.2 equiv) were added to the reaction tube, and N,N-dimethylformamide (20 mL) was added to the above system using a syringe. After the addition was completed, the reactants were placed at room temperature for 5 h. After the reaction was completed, compound 5s (2.39 g, 11.10 mmol, 1.2 equiv) was added to the reaction solution, and then placed at room temperature for 12 h. After the reaction was completed, the solution was extracted three times with ethyl acetate and water, and the organic phases were combined and dried over anhydrous sodium sulfate. After standing for 10 min, the organic phase was filtered out, and the organic solvent was removed by rotary evaporation under reduced pressure. Finally, the product was purified by column chromatography (petroleum ether:ethyl acetate=2:1, v / v) to obtain the target product 6s (1.87 g, yield: 93%).

[0156] 1 H NMR (400MHz, CDCl3): δ7.38-7.26 (m, 5H), 4.56 (s, 2H), 3.92 (dd, J = 5.8, 4.8Hz, 2H), 3.27-3.18 (m, 2H).

[0157] IR(neat):2869,2260,2132,1469,1454,1363,1331,1287cm -1 .

[0158] HR-MS (ESI-TOF) m / z: theoretical value 240.0744 [M+Na] + , the measured value is 240.0745.

[0159] Embodiment 11:

[0160]

[0161] Under nitrogen protection, at room temperature, compound 3a (2 g, 9.25 mmol, 1 equiv) prepared according to the method in Example 1, p-toluene thiophenol (1.38 g, 11.10 mmol, 1.2 equiv) and potassium carbonate (1.53 g, 11.10 mmol, 1.2 equiv) were added to the reaction tube, and N,N-dimethylformamide (20 mL) was added to the above system by syringe. After the addition was completed, the reactants were placed at room temperature for 5 h. After the reaction was completed, compound 5t (2.49 g, 11.10 mmol, 1.2 equiv) was added to the reaction solution, and then placed at room temperature for 12 h. After the reaction was completed, the solution was extracted three times with ethyl acetate and water, and the organic phases were combined and dried over anhydrous sodium sulfate. After standing for 10 min, the organic phase was filtered out, and the organic solvent was removed by rotary evaporation under reduced pressure. Finally, the product was purified by column chromatography (petroleum ether:ethyl acetate=2:1, v / v) to obtain the target product 6t (1.4 g, yield: 67%).

[0162] 1 H NMR (400MHz, CDCl3): δ8.16(s,1H),7.62-7.57(m,1H),7.42-7.37(m,1H),7 .26-7.21(m,1H),7.19-7.12(m,1H),7.10-7.06(m,1H),3.40-3.32(m,4H).

[0163] IR(neat):3743,2368,2318,2085,1741,1724,1706,1646cm -1 .

[0164] HR-MS (ESI-TOF) m / z: theoretical value 249.0748 [M+Na] + , the measured value is 249.0752.

[0165] Embodiment 12:

[0166]

[0167] Under nitrogen protection, at room temperature, compound 3a (2 g, 9.25 mmol, 1 equiv) prepared according to the method in Example 1, p-toluene thiophenol (1.38 g, 11.10 mmol, 1.2 equiv) and potassium carbonate (1.53 g, 11.10 mmol, 1.2 equiv) were added to the reaction tube, and N,N-dimethylformamide (20 mL) was added to the above system by syringe. After the addition was completed, the reactants were placed at room temperature for 5 h. After the reaction was completed, compound 5u (1.83 g, 11.10 mmol, 1.2 equiv) was added to the reaction solution, and then placed at room temperature for 12 h. After the reaction was completed, the solution was extracted three times with ethyl acetate and water, and the organic phases were combined and dried over anhydrous sodium sulfate. After standing for 10 min, the organic phase was filtered out, and the organic solvent was removed by rotary evaporation under reduced pressure. Finally, the product was purified by column chromatography (petroleum ether:ethyl acetate=2:1, v / v) to obtain the target product 6u (773.01 mg, yield: 50%).

[0168] 1 H NMR (400MHz, CDCl3): δ4.56 (dddd, J=9.1, 8.3, 7.4, 0.9Hz, 1H), 4.44 (tdd, J=8.8, 4.8, 0.9Hz, 1 H), 4.00 (ddd, J=10.1, 5.3, 0.9Hz, 1H), 2.98 (ddt, J=14.4, 8.2, 5.0Hz, 1H), 2.78-2.63 (m, 1H).

[0169] IR(neat):3743,2367,2319,1752,1706,1694,1646cm -1 .

[0170] HR-MS (ESI-TOF) m / z: theoretical value 190.0224 [M+Na] + , the measured value is 190.0226.

[0171] Embodiment 13:

[0172]

[0173] Under nitrogen protection, at room temperature, compound 3a (2 g, 9.25 mmol, 1 equiv) prepared according to the method in Example 1, p-toluene thiophenol (1.38 g, 11.10 mmol, 1.2 equiv) and potassium carbonate (1.53 g, 11.10 mmol, 1.2 equiv) were added to the reaction tube, and N, N-dimethylformamide (20 mL) was added to the above system using a syringe. After the addition was completed, the reactants were placed at room temperature for 5 h. After the reaction was completed, compound 5y (3.79 g, 11.10 mmol, 1.2 equiv) was added to the reaction solution, and then placed at room temperature for 12 h. After the reaction was completed, the solution was extracted three times with ethyl acetate and water, the organic phases were combined, and dried over anhydrous sodium sulfate. After standing for 10 min, the organic phase was filtered out, and the organic solvent was removed by rotary evaporation under reduced pressure. Finally, the product was purified by column chromatography (petroleum ether:ethyl acetate=2:1, v / v) to obtain the target product 6y (2.06 g, yield: 65%).

[0174] 1 H NMR (400MHz, CDCl3): δ7.22-7.14(m,2H),7.12-7.04(m,2H),4.16-4.06(m,2H),3.68(q,J=7.2Hz,1H),2.96-2.87 (m,2H),2.43(d,J=7.2Hz,2H),1.86-1.81(m,1H),1.81-1.71(m,4H),1.48(d,J=7.1Hz,3H),0.89(d,J=6.6Hz,6H).

[0175] IR(neat):2954,2869,2266,2132,1727,1510,1457,1294cm -1 .

[0176] HR-MS (ESI-TOF) m / z: theoretical value 366.1789 [M+Na] + , the measured value is 366.1774.

[0177] Embodiment 14:

[0178]

[0179] Under nitrogen protection, at room temperature, compound 3a (2 g, 9.25 mmol, 1 equiv) prepared according to the method in Example 1, p-toluene thiophenol (1.38 g, 11.10 mmol, 1.2 equiv) and potassium carbonate (1.53 g, 11.10 mmol, 1.2 equiv) were added to the reaction tube, and N, N-dimethylformamide (20 mL) was added to the above system by syringe. After the addition was completed, the reactants were placed at room temperature for 5 h. After the reaction was completed, compound 5z (3.9 g, 11.10 mmol, 1.2 equiv) was added to the reaction solution, and then placed at room temperature for 12 h. After the reaction was completed, the solution was extracted three times with ethyl acetate and water, the organic phases were combined, and dried over anhydrous sodium sulfate. After standing for 10 min, the organic phase was filtered out, the organic solvent was removed by vacuum rotary evaporation, and finally purified by column chromatography (petroleum ether: ethyl acetate = 2:1, v / v) to obtain the target product 6z (1.7 g, yield: 52%).

[0180] 1 H NMR (400MHz, CDCl3): δ7.57-7.48(m,2H),7.48-7.34(m,4H),7.17-7.06(m,2H),4.54(qdd,J=12.4 ,6.4,5.0Hz,2H),3.78(q,J=7.2Hz,1H),3.26(ddd,J=6.7,5.1,1.7Hz,2H),1.56(d,J=7.2Hz,3H).

[0181] IR(neat):2962,2920,2261,2133,1733,1644,1683,1483cm -1 .

[0182] HR-MS (ESI-TOF) m / z: theoretical value 354.1249 [M+H] + , the measured value is 354.1238.

[0183] Embodiment 15:

[0184]

[0185] Under nitrogen protection, at room temperature, compound 3a (2 g, 9.25 mmol, 1 equiv) prepared according to the method in Example 1, p-toluene thiophenol (1.38 g, 11.10 mmol, 1.2 equiv) and potassium carbonate (1.53 g, 11.10 mmol, 1.2 equiv) were added to the reaction tube, and N,N-dimethylformamide (20 mL) was added to the above system by syringe. After the addition was completed, the reactants were placed at room temperature for 5 h. After the reaction was completed, compound 5aa (3.96 g, 11.10 mmol, 1.2 equiv) was added to the reaction solution, and then placed at room temperature for 12 h. After the reaction was completed, the solution was extracted three times with ethyl acetate and water, and the organic phases were combined and dried over anhydrous sodium sulfate. After standing for 10 min, the organic phase was filtered out, and the organic solvent was removed by rotary evaporation under reduced pressure. Finally, the product was purified by column chromatography (petroleum ether:ethyl acetate=2:1, v / v) to obtain the target product 6aa (1.73 g, yield: 52%).

[0186] 1 H NMR (400MHz, CDCl3): δ7.01(d,J=7.4Hz,1H),6.67(d,J=7.5Hz,1H),6.61(d,J=1.6Hz,1H),4.50(t,J=5.9Hz,2 H), 3.93 (p, J = 2.7Hz, 2H), 3.29 (t, J = 5.9Hz, 2H), 2.31 (s, 3H), 2.17 (s, 3H), 1.74 (d, J = 3.0Hz, 4H), 1.24 (s, 6H).

[0187] IR(neat):2968,2924,2246,2132,1729,1614,1584,1508cm -1 .

[0188] HR-MS (ESI-TOF) m / z: theoretical value 382.1738 [M+Na] + , the measured value is 382.1725.

[0189] Embodiment 16:

[0190]

[0191] Under nitrogen protection, at room temperature, compound 3a (2 g, 9.25 mmol, 1 equiv) prepared according to the method in Example 1, p-toluene thiophenol (1.38 g, 11.10 mmol, 1.2 equiv) and potassium carbonate (1.53 g, 11.10 mmol, 1.2 equiv) were added to the reaction tube, and N,N-dimethylformamide (20 mL) was added to the above system by syringe. After the addition was completed, the reactants were placed at room temperature for 5 h. After the reaction was completed, compound 5ab (5.18 g, 11.10 mmol, 1.2 equiv) was added to the reaction solution, and then placed at room temperature for 12 h. After the reaction was completed, the solution was extracted three times with ethyl acetate and water, and the organic phases were combined and dried over anhydrous sodium sulfate. After standing for 10 min, the organic phase was filtered out, and the organic solvent was removed by rotary evaporation under reduced pressure. Finally, the product was purified by column chromatography (petroleum ether:ethyl acetate=2:1, v / v) to obtain the target product 6ab (2.25 g, yield: 52%).

[0192] 1 H NMR (400MHz, CDCl3): δ7.71-7.60(m,2H),7.51-7.43(m,2H),6.92(d,J=2.5Hz,1H),6.85(d,J=9.0Hz,1H),6 .67(dd,J=9.0,2.5Hz,1H),4.54(t,J=5.7Hz,2H),3.83(s,3H),3.72(s,2H),3.29-3.22(m,2H),2.37(s,3H).

[0193] IR(neat):2999,2942,2920,2260,2131,1717,1667,1603,1467cm -1 .

[0194] HR-MS (ESI-TOF) m / z: theoretical value 489.0937 [M+Na] + , the measured value is 489.0941.

[0195] As described above, the present invention not only provides an efficient, green and convenient method for preparing deuterated methyl heteroaryl sulfone compounds, but also studies have found that deuterated methyl heteroaryl sulfone compounds can be used to introduce deuterated methyl sulfone groups into a variety of complex compounds.

[0196] It should be noted that, although the technical solution of the present invention is introduced with specific examples, those skilled in the art will appreciate that the present invention should not be limited thereto.

[0197] The embodiments of the present invention have been described above, and the above description is exemplary, not exhaustive, and is not limited to the disclosed embodiments. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the described embodiments. The selection of terms used herein is intended to best explain the principles of the embodiments, practical applications, or technical improvements in the market, or to enable other persons of ordinary skill in the art to understand the embodiments disclosed herein.

Claims

1. A compound of formula I, in: R1, R2, R3 and R4 are each independently hydrogen, C1-C6 alkyl, deuterated C1-C6 alkyl, C1-C6 alkanoyl, C1-C6 alkanoyloxy, C1-C6 alkoxycarbonyl or C6-C 12 Aryl; preferably, R1, R2, R3 and R4 are each independently hydrogen, C1-C3 alkyl, deuterated C1-C3 alkyl, C1-C3 alkanoyl, C1-C3 alkanoyloxy, C1-C3 alkoxycarbonyl or phenyl; more preferably, R1, R2, R3 and R4 are each independently hydrogen or C1-C3 alkyl; further preferably, R1, R2, R3 and R4 are each independently hydrogen or methyl; A is S or O; preferably, A is S.

2. The compound according to claim 1, which is selected from the following compounds: Preferably, the compound is selected from the following compounds:

3. A method for preparing the compound according to claim 1, comprising the following steps: (1) Under the protection of an inert gas, compound II reacts with a deuterated methylation reagent to obtain compound III. (2) Compound III reacts with an oxidant to obtain Compound I, in, A, R1, R2, R3 and R4 are as defined in claim 1.

4. The preparation method according to claim 3, characterized in that: In step (1), The deuterated methylation agent is at least one of deuterated iodomethane, deuterated dimethyl sulfate and deuterated methyl trifluoromethanesulfonate, preferably deuterated iodomethane; and / or, The molar ratio of the compound II to the deuterated methylation agent is 1:1 to 1:3, preferably 1:1.2; and / or, The reaction is carried out in the presence of a base; Preferably, the base is an inorganic base, preferably at least one of potassium carbonate, sodium carbonate, potassium hydroxide and sodium hydroxide, more preferably potassium carbonate; and / or, The molar ratio of the compound II to the base is 1:1.2 to 1:5, preferably 1:1.

2.

5. The preparation method according to claim 3 or 4, characterized in that: In step (1), The inert gas is nitrogen; and / or, The reaction is carried out in a polar aprotic solvent; Preferably, the polar aprotic solvent is at least one of N,N-dimethylformamide, 1,4-dioxane, tetrahydrofuran and acetonitrile, preferably N,N-dimethylformamide; and / or, The usage ratio of the compound II to the polar aprotic solvent is 1 g:10 mL to 1 g:40 mL, preferably 1 g:20 mL.

6. The preparation method according to any one of claims 3 to 5, characterized in that: In step (1), The reaction temperature is 0°C to 25°C, preferably 25°C; and / or, The reaction time is 4 h to 12 h, preferably 12 h.

7. The preparation method according to any one of claims 3 to 6, characterized in that: In step (2), The oxidant is at least one of hydrogen peroxide or its aqueous solution and m-chloroperbenzoic acid, preferably an aqueous hydrogen peroxide solution, more preferably a 30% by mass aqueous hydrogen peroxide solution; and / or, Calculated on the basis of hydrogen peroxide or meta-chloroperbenzoic acid, the molar ratio of the compound III to the oxidant is 1:3 to 1:20, preferably 1:10; and / or, The reaction is carried out in the presence of a catalyst; Preferably, the catalyst is at least one of ammonium molybdate tetrahydrate, sodium tungstate dihydrate and ethylenediaminetetraacetic acid, preferably ammonium molybdate tetrahydrate; and / or, The molar ratio of the compound III to the catalyst is 1:0.01 to 1:0.8, preferably 1:0.

1.

8. The preparation method according to any one of claims 3 to 7, characterized in that: In step (2), The reaction is carried out in a polar organic solvent; Preferably, the polar organic solvent is at least one of alcohols and nitriles, preferably alcohols, more preferably at least one of methanol and ethanol, further preferably ethanol; and / or, the dosage ratio of the compound III to the polar organic solvent is 1g:10mL to 1g:40mL, preferably 1g:20mL.

9. The preparation method according to any one of claims 3 to 8, characterized in that: In step (2), The reaction temperature is 0°C to 25°C, preferably 25°C; and / or, The reaction time is 8 h to 16 h, preferably 12 h.

10. Use of the compound according to claim 1 or 2 in a deuterated mesylation reaction of a substrate, Preferably, in the deuterated mesylation reaction, the compound is used as a deuterated mesylate donor reagent; and / or, Preferably, the substrate contains a leaving group; More preferably, the leaving group is halogen, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy, preferably halogen, more preferably bromine.

11. A method for introducing a deuterated methylsulfonyl group into a substrate, comprising the steps of: (1) reacting the compound according to claim 1 or 2 and p-toluene thiophenol in a polar aprotic solvent under the action of a base to obtain a reaction solution; (2) adding the substrate to the reaction solution of step (1) to carry out a reaction to obtain a deuterated methylsulfonyl-substituted substrate; Preferably, the substrate contains a leaving group; More preferably, the leaving group is halogen, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy, preferably halogen, more preferably bromine.

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