A deuterated methyl enamine ketone compound and a preparation method thereof

Abstract

The present application belongs to the field of chemical synthesis, and relates to a kind of deuterated methyl-containing enamine ketone compound and preparation method thereof. 3-azido high allyl alcohol derivative is mixed with 5-(deuterated methyl) 5H-thianthrene-5-triflate, photocatalyst, base and solvent to obtain a homogeneous solution; the homogeneous solution is placed in a reaction tube provided with a light source to carry out reaction, and a deuterated methyl-containing enamine ketone compound is obtained. In the preparation method provided by the present application, the reagent used has small pollution, high safety and simple experimental operation, which improves the apparent reaction rate and the selectivity of the product, and is beneficial to large-scale continuous production. In the preparation method of the present application, no expensive transition metal catalyst is used, which greatly reduces the reaction cost and solves the environmental pollution problem caused by post-processing. The method provided by the present application can not only realize the deuterated methylation of 3-azido high allyl alcohol derivative, but also can be further derived to the double functionalization of unsaturated bond.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of chemical synthesis, and relates to a deuterated methyl enaminone compound and a preparation method thereof. BACKGROUND

[0002] Nitrogen-containing compounds, as the basic structural unit of many natural products and the advantage skeleton of active drug molecules, are one of the important research focuses in organic synthesis and innovative drug research. Enaminone compounds, as a unique nitrogen-containing compound, have great application prospects in the artificial synthesis of natural organic compounds and the construction of drug intermediates.

[0003] Methyl exists in various structural units and commercial drugs, representing one of the simplest organic substituents in drug research and development. The addition of methyl in candidate drugs can significantly improve the biological activity, pharmacokinetic properties and physical properties of drugs by adjusting the solubility, hydrophilicity and conformation of drugs. This change has been proved to increase the efficacy of lead compounds by more than 2000 times. Therefore, the importance of methods for realizing selective methyl substitution at specific positions is increasing.

[0004] Deuterium, as the most accessible stable non-radioactive isotope of hydrogen, is widely used in drug discovery and development. Since the C-D bond is more stable than the C-H bond, deuterium substitution of hydrogen can change the properties of candidate drugs, including absorption, distribution, metabolism and excretion. Various deuterium-labeled candidate drugs have been developed and submitted for clinical trials. The introduction of deuterated methyl functional groups first requires the identification of a viable "CD" source. Komarapuri, S et al. reported in 2008 that C-19 was introduced before the A-ring closure of a steroid by using deuterated iodomethane (99.5% d(3)), which produced 19,19,19-trideuterated steroids without increasing the number of steps involved in the total synthesis of ent-androgens (J. Labelled Compd. Radiopharm. 2008, 51, 430-434). Jiang, X. et al. reported in 2014 a general method for N-deuteromethylation of amines and nitro compounds using deuterated dimethyl sulfoxide (Chem.-A Eur. J. 2014, 20, 58-63). However, deuterated methylation reagents are a major obstacle to the evolution of deuterated methylation reactions. Deuterated iodomethane, deuterated reducing agents and d6-DMSO solutions have been widely used as deuterated methylation reagents, but they have great disadvantages in volatility, corrosiveness, toxicity and carcinogenicity. In order to solve these limitations, it is crucial to develop deuterated methylation reagents that can complete direct, scalable and selective deuterated methylation under mild conditions. SUMMARY

[0005] The technical problem solved by the present application is to provide a deuterated methylation reagent and a method for preparing a deuterated methyl-containing enamine ketone compound based on visible light catalysis.

[0006] To solve the above technical problems, the technical scheme adopted by the present application is as follows:

[0007] To solve the above technical problems, the present application discloses a deuterated methylation reagent, and the structure of the deuterated methylation reagent is as follows:

[0008]

[0009] In some embodiments, formic acid and deuterated methanol are subjected to a first reaction under the action of an acid, and then subjected to a second reaction with thianthrene and trifluoromethanesulfonic acid, and the deuterated methyl-containing enamine ketone compound is obtained.

[0010] In some embodiments, the acid is concentrated sulfuric acid, concentrated hydrochloric acid or concentrated phosphoric acid; the molar ratio of formic acid, deuterated methanol, acid, thianthrene and trifluoromethanesulfonic acid is 3-5:8-10:3-5:1-3:4-9; the reaction temperature of the first reaction is 50-80 DEG C, and the reaction time is 3-5 h; the reaction temperature of the second reaction is 20-40 DEG C.

[0011] In some embodiments, preferably, the acid is concentrated sulfuric acid; the molar ratio of formic acid, deuterated methanol, acid, thianthrene and trifluoromethanesulfonic acid is 3-4:8-9:3-4:1-2:5-7, and further preferably 3.5:8.2:3.1:1:6; the reaction temperature of the first reaction is 50-70 DEG C, and further preferably 60 DEG C, and the reaction time is 4 h; the reaction temperature of the second reaction is 30 DEG C.

[0012] The application of the above-mentioned deuterated methylation reagent in a deuterated methylation reaction is also within the protection scope of the present application.

[0013] Further, the present application discloses a deuterated methyl-containing enamine ketone compound, and the structural formula of the deuterated methyl-containing enamine ketone compound is as follows:

[0014]

[0015] Among them,

[0016] R 1 is selected from substituted or unsubstituted aryl, or substituted or unsubstituted aromatic heterocyclic group; wherein the substitution is substituted by one or more same or different groups; the substitution is selected from any one or several groups of halogen, aryl, cyano and C1-C4 alkoxy;

[0017] R 2substituted or unsubstituted aromatic heterocyclic group; wherein said substitution is substituted with one or more of the same or different groups; and said substitution is selected from the group consisting of oxo C1-C4 alkoxy substituted with C1-C4 alkyl, or aliphatic heterocyclic group.

[0018] In some embodiments, preferably,

[0019] R 1 substituted or unsubstituted phenyl, unsubstituted naphthyl, or substituted pyridyl; wherein said substitution is substituted with one or more of the same or different groups; and said substitution is selected from the group consisting of any one or several of chloro, bromo, phenyl, cyano, and C1-C2 alkoxy;

[0020] R 2 substituted or unsubstituted benzothiazolyl, substituted thiazolyl, or benzoxazolyl; wherein said substitution is substituted with one or more of the same or different groups; and said substitution is selected from the group consisting of oxo C1-C2 alkoxy substituted with C1-C2 alkyl, or morpholinyl.

[0021] In some embodiments, further preferably,

[0022] R 1 substituted or unsubstituted phenyl, unsubstituted naphthyl, or substituted pyridyl; wherein said substitution is substituted with one or more of the same or different groups; and said substitution is selected from the group consisting of any one or several of chloro, bromo, phenyl, cyano, and C1-C2 alkoxy;

[0023] R 2 substituted or unsubstituted benzothiazolyl, substituted thiazolyl, or benzoxazolyl; wherein said substitution is substituted with one or more of the same or different groups; and said substitution is selected from the group consisting of oxo C1-C2 alkoxy substituted with C1-C2 alkyl, or morpholinyl.

[0024] Further, the present application discloses a preparation method of the above-mentioned deuterated methyl-containing enaminone compound, which comprises the following steps: mixing 3-azido homoallyl derivative 1, 5-(deuterated methyl) 5H-thianthrene-5-triflate 2, a photocatalyst, a base and a solvent to obtain a homogeneous solution; and reacting the homogeneous solution in a reaction tube provided with a light source to obtain the deuterated methyl-containing enaminone compound 3.

[0025] wherein the structure of the 3-azido homoallyl derivative 1 is shown as formula 1, the structure of the 5-(deuterated methyl) 5H-thianthrene-5-triflate 2 is shown as formula 2, and the structure of the deuterated methyl-containing enaminone compound 3 is shown as formula 3.

[0026]

[0027] wherein R is selected from the group consisting of substituted or unsubstituted aryl, or substituted or unsubstituted heteroaromatic group; wherein said substitution is by one or more of the same or different groups; and wherein said substitution is selected from any one or more of halogen, aryl, cyano, and C1-C4 alkoxy groups; 1 wherein R is selected from the group consisting of substituted or unsubstituted aryl, or substituted or unsubstituted heteroaromatic group; wherein said substitution is by one or more of the same or different groups; and wherein said substitution is selected from any one or more of halogen, aryl, cyano, and C1-C4 alkoxy groups;

[0028] wherein R is selected from the group consisting of substituted or unsubstituted aryl, or substituted or unsubstituted heteroaromatic group; wherein said substitution is by one or more of the same or different groups; and wherein said substitution is selected from any one or more of halogen, aryl, cyano, and C1-C4 alkoxy groups; 2 wherein R is selected from the group consisting of substituted or unsubstituted aryl, or substituted or unsubstituted heteroaromatic group; wherein said substitution is by one or more of the same or different groups; and wherein said substitution is selected from any one or more of halogen, aryl, cyano, and C1-C4 alkoxy groups;

[0029] wherein R is selected from the group consisting of substituted or unsubstituted aryl, or substituted or unsubstituted heteroaromatic group; wherein said substitution is by one or more of the same or different groups; and wherein said substitution is selected from any one or more of halogen, aryl, cyano, and C1-C4 alkoxy groups;

[0030] wherein R is selected from the group consisting of substituted or unsubstituted aryl, or substituted or unsubstituted heteroaromatic group; wherein said substitution is by one or more of the same or different groups; and wherein said substitution is selected from any one or more of halogen, aryl, cyano, and C1-C4 alkoxy groups; 1 wherein R is selected from the group consisting of substituted or unsubstituted aryl, or substituted or unsubstituted heteroaromatic group; wherein said substitution is by one or more of the same or different groups; and wherein said substitution is selected from any one or more of halogen, aryl, cyano, and C1-C4 alkoxy groups;

[0031] wherein R is selected from the group consisting of substituted or unsubstituted aryl, or substituted or unsubstituted heteroaromatic group; wherein said substitution is by one or more of the same or different groups; and wherein said substitution is selected from any one or more of halogen, aryl, cyano, and C1-C4 alkoxy groups; 2 wherein R is selected from the group consisting of substituted or unsubstituted aryl, or substituted or unsubstituted heteroaromatic group; wherein said substitution is by one or more of the same or different groups; and wherein said substitution is selected from any one or more of halogen, aryl, cyano, and C1-C4 alkoxy groups;

[0032] wherein R is selected from the group consisting of substituted or unsubstituted aryl, or substituted or unsubstituted heteroaromatic group; wherein said substitution is by one or more of the same or different groups; and wherein said substitution is selected from any one or more of halogen, aryl, cyano, and C1-C4 alkoxy groups;

[0033] wherein R is selected from the group consisting of substituted or unsubstituted aryl, or substituted or unsubstituted heteroaromatic group; wherein said substitution is by one or more of the same or different groups; and wherein said substitution is selected from any one or more of halogen, aryl, cyano, and C1-C4 alkoxy groups; 1 wherein R is selected from the group consisting of substituted or unsubstituted aryl, or substituted or unsubstituted heteroaromatic group; wherein said substitution is by one or more of the same or different groups; and wherein said substitution is selected from any one or more of halogen, aryl, cyano, and C1-C4 alkoxy groups;

[0034] wherein R is selected from the group consisting of substituted or unsubstituted aryl, or substituted or unsubstituted heteroaromatic group; wherein said substitution is by one or more of the same or different groups; and wherein said substitution is selected from any one or more of halogen, aryl, cyano, and C1-C4 alkoxy groups; 2 wherein R is selected from the group consisting of substituted or unsubstituted aryl, or substituted or unsubstituted heteroaromatic group; wherein said substitution is by one or more of the same or different groups; and wherein said substitution is selected from any one or more of halogen, aryl, cyano, and C1-C4 alkoxy groups;

[0035] wherein R is selected from the group consisting of substituted or unsubstituted aryl, or substituted or unsubstituted heteroaromatic group; wherein said substitution is by one or more of the same or different groups; and wherein said substitution is selected from any one or more of halogen, aryl, cyano, and C1-C4 alkoxy groups;

[0036]

[0037] wherein R is selected from the group consisting of substituted or unsubstituted aryl, or substituted or unsubstituted heteroaromatic group; wherein said substitution is by one or more of the same or different groups; and wherein said substitution is selected from any one or more of halogen, aryl, cyano, and C1-C4 alkoxy groups;

[0038]

[0039] In some embodiments, the photocatalyst is any one or a combination of several of tris(2-(4-fluorophenyl)pyridine)iridium, (4,4'-di-tert-butyl-2,2'-bipyridine)bis[(2-pyridyl)phenyl]iridium(III) hexafluorophosphate, graphitic nitrogen, 10-methyl-9-mesityl acridinium perchlorate, tris(2,2'-bipyridyl)dichlororuthenium, tris(2,2'-bipyridyl)ruthenium bis(hexafluorophosphate), tris[2-(2,4-difluorophenyl)pyridine]iridium(III), and tris(2-phenylpyridyl)iridium; the base is any one or a combination of several of sodium carbonate, dipotassium hydrogen phosphate, sodium bicarbonate, cesium carbonate, cesium acetate, and potassium methoxide; and the solvent is any one or a combination of several of deuterated methanol, toluene, ethyl acetate, dichloroethane, tetrahydrofuran, 1,4-dioxane, dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, diethyl ether, and acetone.

[0040] In some embodiments, preferably, the photocatalyst is tris[2-(2,4-difluorophenyl)pyridine]iridium(III) or tris(2-phenylpyridyl)iridium, further preferably tris(2-phenylpyridyl)iridium.

[0041] In some embodiments, preferably, the base is sodium carbonate or dipotassium hydrogen phosphate, further preferably sodium carbonate.

[0042] In some embodiments, preferably, the solvent is deuterated methanol or acetone, further preferably acetone.

[0043] In some embodiments, the molar ratio of the 3-azido homoallyl derivative 1 to 5-(deuterated methyl)5H-thianthrene-5-triflate 2, photocatalyst, base is 1:1~5:0.01~0.03:1~2; and the concentration of the 3-azido homoallyl derivative 1 in the homogeneous solution is 0.05~1.00 mmol / mL.

[0044] In some embodiments, preferably, the molar ratio of the 3-azido homoallyl derivative 1 to 5-(deuterated methyl)5H-thianthrene-5-triflate 2, photocatalyst, base is 1:1~3:0.01~0.03:1~2.

[0045] In some embodiments, further preferably, the molar ratio of the 3-azido homoallyl derivative 1 to 5-(deuterated methyl)5H-thianthrene-5-triflate 2, photocatalyst, base is 1:2:0.02:2.

[0046] In some embodiments, preferably, the concentration of the 3-azido homoallyl derivative 1 in the homogeneous solution is 0.1-0.5 mmol / mL, and more preferably 0.1 mmol / mL.

[0047] In some embodiments, the homogeneous solution is placed in a reaction tube provided with a blue LED light source for reaction, and the light source is a lamp strip or a bulb, the power of the light source is 5-60 W, and the wavelength of the light source is 400-760 nm.

[0048] In some embodiments, preferably, the homogeneous solution is placed in a reaction tube provided with a blue LED light source for reaction, and the light source is a lamp strip or a bulb, the power of the light source is 40-60 W, and the wavelength of the light source is 450-470 nm.

[0049] In some embodiments, more preferably, the homogeneous solution is placed in a reaction tube provided with a blue LED light source for reaction, and the light source is a lamp strip or a bulb, the power of the light source is 50 W, and the wavelength of the light source is 455 nm.

[0050] In some embodiments, the reaction is carried out under the protection of an inert gas.

[0051] Preferably, the inert gas is argon.

[0052] In some embodiments, the reaction is carried out at a temperature of 20-30 DEG C for 10-14 h.

[0053] In some embodiments, preferably, the reaction is carried out at a temperature of 25 DEG C for 12 h.

[0054] In summary, the present application provides a method for preparing a deuterated methyl enamine ketone compound based on visible light catalysis, and the method comprises the following steps: dissolving 3-azido homoallyl derivative and 5-(deuterated methyl) 5H-thianthrene-5-triflate in a suitable solvent, adding a photocatalyst and a base, and carrying out deuterated methyl reaction of the 3-azido homoallyl derivative under the irradiation of visible light.

[0055] Advantages:

[0056] (1) The reagent used in the preparation method provided by the present application has small pollution, high safety and simple experimental operation, which improves the apparent reaction rate and the selectivity of the product, and is beneficial to large-scale continuous production.

[0057] (2) The preparation method provided by the present application does not need to use expensive transition metal catalysts, greatly reduces the reaction cost, and solves the environmental pollution problem caused by post-processing.

[0058] (3) The light source used in the index method of the present application is visible light, which is a sustainable energy source and meets the development concept of green chemistry.

[0059] (4) The method provided by the present application can not only realize deuterated methylation of 3-azido homoallyl derivatives, but also can further derive to the bifunctionalization of unsaturated bonds.

[0060] (5) The deuterated methylation reagent used in the present application can be synthesized by cheap and readily available raw materials through simple steps, avoiding the use of deuterated methylation reagents with strong pollution in the original method.

[0061] (6) The yield of the deuterated methyl-containing oleamine ketone compound obtained by the preparation method of the present application can reach 55% to 78%. BRIEF DESCRIPTION OF DRAWINGS

[0062] The above and / or other aspects of the present application will become more apparent by describing in detail the preferred embodiments thereof with reference to the attached drawings, in which:

[0063] Figure 1 The hydrogen spectrum of the compound (Z)-3-(benzothiazol-2-ylamino)-1-phenyl-2-penten-1-one-5,5,5-d3 prepared for Example 2.

[0064] Figure 2 The carbon spectrum of the compound (Z)-3-(benzothiazol-2-ylamino)-1-phenyl-2-penten-1-one-5,5,5-d3 prepared for Example 2.

[0065] Figure 3 The hydrogen spectrum of the compound (Z)-3-(benzothiazol-2-ylamino)-1-(4-bromophenyl)pent-2-en-1-one-5,5,5-d3 prepared for Example 3.

[0066] Figure 4 The carbon spectrum of the compound (Z)-3-(benzothiazol-2-ylamino)-1-(4-bromophenyl)pent-2-en-1-one-5,5,5-d3 prepared for Example 3.

[0067] Figure 5 The hydrogen spectrum of the compound (Z)-1-([1,1'-biphenyl]-4-yl)-3-(benzothiazol-2-ylamino)pent-2-en-1-one-5,5,5-d3 prepared for Example 4.

[0068] Figure 6 The carbon spectrum of the compound (Z)-1-([1,1'-biphenyl]-4-yl)-3-(benzothiazol-2-ylamino)pent-2-en-1-one-5,5,5-d3 prepared for Example 4.

[0069] Figure 7 The hydrogen spectrum of the compound (Z)-4-(3-(benzothiazol-2-ylamino)pent-2- enoyl-5,5,5-d3)benzonitrile prepared for Example 5.

[0070] Figure 8 The carbon spectrum of the compound (Z)-4-(3-(benzothiazol-2-ylamino)pent-2- enoyl-5,5,5-d3)benzonitrile prepared for Example 5.

[0071] Figure 9 The hydrogen spectrum of the compound (Z)-3-(benzothiazol-2-ylamino)-1-(3,4,5- trimethoxyphenyl)pent-2-en-1-one-5,5,5-d3 prepared for Example 6.

[0072] Figure 10 The carbon spectrum of the compound (Z)-3-(benzothiazol-2-ylamino)-1-(3,4,5- trimethoxyphenyl)pent-2-en-1-one-5,5,5-d3 prepared for Example 6.

[0073] Figure 11 The hydrogen spectrum of the compound (Z)-3-(benzothiazol-2-ylamino)-1-(2,5- dichlorophenyl)pent-2-en-1-one-5,5,5-d3 prepared for Example 7.

[0074] Figure 12 The carbon spectrum of the compound (Z)-3-(benzothiazol-2-ylamino)-1-(2,5- dichlorophenyl)pent-2-en-1-one-5,5,5-d3 prepared for Example 7.

[0075] Figure 13 The hydrogen spectrum of the compound (Z)-3-(benzothiazol-2-ylamino)-1-(naphthalen- 2-yl)pent-2-en-1-one-5,5,5-d3 prepared for Example 8.

[0076] Figure 14 The carbon spectrum of the compound (Z)-3-(benzothiazol-2-ylamino)-1-(naphthalen- 2-yl)pent-2-en-1-one-5,5,5-d3 prepared for Example 8.

[0077] Figure 15 The hydrogen spectrum of the compound (Z)-3-(benzothiazol-2-ylamino)-1-(6- chloropyridin-3-yl)pent-2-en-1-one-5,5,5-d3 prepared for Example 9.

[0078] Figure 16Carbon spectrum of the compound (Z)-3-(benzothiazol-2-ylamino)-1-(6- chloropyridin-3-yl)pent-2-en-1-one-5,5,5-d3 prepared for Example 9.

[0079] Figure 17 Hydrogen spectrum of the compound (Z)-3-((4-methylbenzothiazol-2-yl)amino)-1- phenyl-2-penten-1-one-5,5,5-d3 prepared for Example 10.

[0080] Figure 18 Carbon spectrum of the compound (Z)-3-((4-methylbenzothiazol-2-yl)amino)-1- phenyl-2-penten-1-one-5,5,5-d3 prepared for Example 10.

[0081] Figure 19 Hydrogen spectrum of the compound (Z)-3-((4,5-dimethylthiazol-2-yl)amino)-1- phenyl-2-penten-1-one-5,5,5-d3 prepared for Example 11.

[0082] Figure 20 Carbon spectrum of the compound (Z)-3-((4,5-dimethylthiazol-2-yl)amino)-1- phenyl-2-penten-1-one-5,5,5-d3 prepared for Example 11.

[0083] Figure 21 Hydrogen spectrum of the compound (Z)-3-((6-(2-morpholino-2-oxoethoxy)benzothiazol- 2-yl)amino)-1-phenyl-2-penten-1-one-5,5,5-d3 prepared for Example 12.

[0084] Figure 22 Carbon spectrum of the compound (Z)-3-((6-(2-morpholino-2-oxoethoxy)benzothiazol- 2-yl)amino)-1-phenyl-2-penten-1-one-5,5,5-d3 prepared for Example 12.

[0085] Figure 23 Hydrogen spectrum of the compound (Z)-3-(benzoxazol-2-ylamino)-1-phenyl-2- penten-1-one-5,5,5-d3 prepared for Example 13.

[0086] Figure 24 Carbon spectrum of the compound (Z)-3-(benzoxazol-2-ylamino)-1-phenyl-2- penten-1-one-5,5,5-d3 prepared for Example 13.

[0087] Figure 25 Hydrogen spectrum of 5-(deuterated methyl)5H-thianthrene-5-triflate prepared for Example 1

[0088] Figure 26 Carbon spectrum of 5-(deuterated methyl) 5H-thianthrene-5-triflate prepared for Example 1.

[0089] Figure 27 Experimental apparatus diagram used in the examples of the present application. DETAILED DESCRIPTION

[0090] The experimental methods described in the following examples are all conventional methods unless otherwise specified; the reagents and materials described are all commercially available unless otherwise specified.

[0091] The 3-azido-containing homoallyl derivative used in the examples of the present application is prepared according to the prior art (Green Chem., 2021, 23, 8916-8921).

[0092] The experimental apparatus diagram used in the examples of the present application is shown in Figure 27 .

[0093] Example 1

[0094]

[0095] Into a 50 mL round flask, formic acid (4.0 mL, 106 mmol) and CD3OD (10.0 mL, 247 mmol, 99% D) were added. Then, sulfuric acid (5.0 mL, 94 mmol, 98%) was added dropwise to the above solution while stirring. The mixture was heated at 60°C and continued for 4 hours. After the reaction was completed, the formic acid-d3 formate containing a small amount of deuterated methanol was directly distilled at normal pressure (33-38°C). Formic acid-d3 was obtained without further purification.

[0096] Into a 100 mL round flask, thianthrene (TT, 30 mmol, 1.0 equivalent) and the above distilled formic acid-d3 formate were added. The mixture was stirred at 0°C, and TfOH (16.0 mL, 180 mmol, 6.0 equivalents) was added dropwise while stirring. Next, the reaction was heated to 30°C and stirred overnight. After the reaction was completed, the reaction was poured into water (50 mL), extracted with CH2Cl2 (50 mL x 3), dried over anhydrous Na2SO4, and concentrated in vacuo. The obtained crude product was washed with Et2O (25 mL x 3) and dried under vacuum to obtain the trideuteromethyl reagent TT-CD3 + OTf - (10.6 g, 92%, 99% D).

[0097] 5-(Deuterated methyl) 5H-thianthrene-5-triflate TT-CD3 + OTf -The characterization data are as follows (e.g.) Figure 25 , Figure 26 As shown): 1 H NMR (400MHz, CDCl3) δ8.37(dd,J=7.8,1.3Hz,2H),7.84(dd,J=7.9,1.2Hz,2H),7.75(td,J=7.7,1.4Hz,2H),7.68(td,J=7.7,1.4Hz,2H). 13 C NMR (100MHz, CDCl3) δ135.6,134.4,134.2,130.2,130.0,118.8. 19 F NMR(376MHz,CDCl3)δ78.25.HRMS(ESI)m / z:calcd for C 13 H8D3S2 + [M–OTf] + :234.0484,found:234.0487.

[0098] Example 2

[0099]

[0100] 64.5 mg (0.2 mmol, 1.0 equiv) of 3-azido-1-(benzothiazol-2-yl)-1-phenyl-3-buten-1-ol, 153.4 mg (0.4 mmol, 2.0 equiv) of 5-(deuterated methyl) 5H-thiaanthracene-5-trifluoromethanesulfonate, 42.3 mg (0.4 mmol, 2.0 equiv) of sodium carbonate, and 2.62 mg (0.004 mmol, 2.0 mmol%) of tris(2-phenylpyridinyl)iridium were weighed and added to a dry Schlenk reaction tube, which was then purged with argon gas three times. 2 mL of deuterated methanol was injected into the Schlenk reaction tube using a syringe. The reaction was carried out at 25 °C for 12 h under blue LED illumination (50 W, 455 nm). After the reaction was completed, TLC was performed. The reaction solution was extracted with ethyl acetate and saturated brine (3 × 25 mL). The organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by vacuum distillation. The final product (Z)-3-(benzothiazol-2-ylamino)-1-phenyl-2-penten-1-one-5,5,5-d3 39.8 mg was obtained by silica gel column chromatography (petroleum ether: ethyl acetate = 10:1), with a yield of 64%.

[0101] The characterization data of product (Z)-3-(benzothiazol-2-ylamino)-1-phenyl-2-penten-1-one-5,5,5-d3 are as follows ( Figure 1 , Figure 2 As shown):1 H NMR (400 MHz, CDC13) δ 13.96 (s, 1H), 8.04 - 7.95 (m, 2H), 7.85 - 7.71 (m, 2H), 7.59 - 7.53 (m, 1H), 7.53 - 7.46 (m, 2H), 7.43 (t, J = 7.4 Hz, 1H), 7.29 (t, J = 7.4 Hz, 1H), 6.18 (s, 1H), 3.17 (s, 2H). 13 C NMR (100 MHz, CDC13) δ 190.9, 164.6, 159.4, 152.0, 139.1, 132.0, 128.6, 127.5, 126.2, 124.0, 121.5, 121.1, 96.9, 27.6. HRMS (ESI) m / z: calcd for C 18 H 13 D3N2OSNa [M+Na] + : 334.1064, found: 334.1059.

[0102] Example 3

[0103]

[0104] Example 3

[0105] The product (Z)-3-(benzothiazol-2-ylamino)-1-(4-bromophenyl)pent-2-en-1-one-5,5,5-d3 was characterized by the following data (1H NMR (400 MHz, CDC13) δ 7.97 (d, J = 8.0 Hz, 2H), 7.86 (d, J = 8.0 Hz, 2H), 7.62 (d, J = 7.9 Hz, 1H), 7.53 (d, J = 7.9 Hz, 1H), 7.48 (t, J = 7.9 Hz, 1H), 7.44 (t, J = 7.9 Hz, 1H), 6.19 (s, 1H), 3.17 (s, 2H).13C NMR (100 MHz, CDC13) δ 190.9, 164.6, 159.4, 152.0, 139.1, 132.0, 128.6, 127.5, 126.2, 124.0, 121.5, 121.1, 96.9, 27.6. HRMS (ESI) m / z: calcd for C Figure 3, Figure 4 As shown): 1 H NMR (400MHz, CDCl3) δ13.82(s,1H),7.77–7.65(m,4H),7.53(d,J=8.4Hz,2H),7.34(t,J=7.6Hz,1H),7.23–7.19(m,1H),6.01(s,1H),3.07(s,2H). 13 C NMR (100MHz, CDCl3) δ189.5,165.2,159.2,151.9,137.9,132.0,131.8,129.1,126.9,126.3,124.1,121.6,121.1,96.4,27.6.HRMS(ESI)m / z:calcd for C 18 H 13 D3BrN2OS[M+H] + :390.0350,found:390.0345.

[0106] Example 4

[0107]

[0108] 79.7 mg (0.2 mmol, 1.0 equiv) of 1-([1,1'-biphenyl]-4-yl)-3-azido-1-(benzothiazol-2-yl)but-3-en-1-ol, 153.4 mg (0.4 mmol, 2.0 equiv) of 5-(deuterated methyl)5H-thiaanthracene-5-trifluoromethanesulfonate, 42.3 mg (0.4 mmol, 2.0 equiv) of sodium carbonate, and 2.62 mg (0.004 mmol, 2.0 mmol%) of tris(2-phenylpyridinyl)iridium were weighed and added to a dry Schlenk reaction tube, and the tube was purged with argon gas three times. 2 mL of deuterated methanol was then injected into the Schlenk reaction tube using a syringe. The reaction was carried out at 25 °C for 12 h under blue LED illumination (50 W, 455 nm). After the reaction was completed, TLC was performed. The reaction solution was extracted with ethyl acetate and saturated brine (3 × 25 mL). The organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by vacuum distillation. The final product (Z)-1-([1,1'-biphenyl]-4-yl)-3-(benzothiazol-2-ylamino)pent-2-en-1-one-5,5,5-d3 60.2 mg was obtained by silica gel column chromatography (petroleum ether: ethyl acetate = 10:1), with a yield of 78%.

[0109] Characterization data for the product (Z)-1-([1,1'-biphenyl]-4-yl)-3-(benzothiazol-2-ylamino)pent-2-en-1-one-5,5,5-d3is as follows: Figure 5 、 Figure 6 1 H NMR (400 MHz, CDC13) δ 13.90 (s, 1H), 7.96 (d, J = 8.4 Hz, 2H), 7.72 - 7.55 (m, 6H), 7.43 - 7.29 (m, 4H), 7.21 - 7.17 (m, 1H), 6.12 (s, 1H), 3.09 (s, 2H). 13 C NMR (100 MHz, CDC13) δ 190.4, 164.6, 159.4, 152.0, 144.7, 140.1, 137.8, 132.0, 129.0, 128.1(1), 128.0(8), 127.3, 127.2, 126.2, 124.0, 121.5, 121.1, 96.9, 27.6. HRMS (ESI) m / z: calcd for C 24 H 17 D3N2OSNa[M+Na] + : 410.1377, found: 410.1374.

[0110] Example 5

[0111]

[0112] ​A mixture of 4-(3-azido-1-(benzothiazol-2-yl)-1-hydroxybut-3-en-1-yl)benzonitrile 69.5 mg (0.2 mmol, 1.0 equiv), 5-(deuteriomethyl)5H-thianaphthalene-5-trifluoromethanesulfonate 153.4 mg (0.4 mmol, 2.0 equiv), sodium carbonate 42.3 mg (0.4 mmol, 2.0 equiv), tris(2-phenylpyridyl)iridium 2.62 mg (0.004 mmol, 2.0 mmol%) was placed in a dry Schlenk tube and purged with argon three times. 2 mL of deuteriomethanol was injected into the Schlenk tube with a syringe. The reaction was carried out at 25 °C under irradiation with a blue LED light source (50 W, 455 nm) for 12 h. After the reaction was completed, TLC detection was performed, and the reaction solution was extracted with ethyl acetate and saturated brine (3 x 25 mL), and the organic layer was combined, dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The final product (Z)-4-(3-(benzothiazol-2-ylamino)pent-2-enoyl-5,5,5-d3)benzonitrile 48.2 mg was obtained by silica gel column chromatography (petroleum ether: ethyl acetate = 10:1) with a yield of 67%. The characterization data are as follows Figure 7 、 Figure 8 1 H NMR (400 MHz, CDCl3) δ 13.90 (s, 1H), 8.03 (d, J = 8.4 Hz, 2H), 7.82-7.74 (m, 4H), 7.46-7.41 (m, 1H), 7.33-7.28 (m, 1H), 6.10 (s, 1H), 3.16 (s, 2H). 13 C NMR (100 MHz, CDCl3) δ 188.5, 166.4, 158.9, 151.8, 142.7, 132.4, 132.1, 127.9, 126.4, 124.3, 121.7, 121.1, 118.3, 115.1, 96.5, 27.6. HRMS (ESI) m / z: calcd for C 19 H 12 D3N3OSNa[M+Na] + : 359.1016, found: 359.1289.

[0113] Example 6

[0114]

[0115] ​A mixture of 1-(3,4,5-trimethoxyphenyl)-3-azido-1-(benzothiazol-2-yl)but-3- en-1-ol 82.5 mg (0.2 mmol, 1.0 equiv), 5-(deuteriomethyl)5H-thianthrene-5- triflate 153.4 mg (0.4 mmol, 2.0 equiv), sodium carbonate 42.3 mg (0.4 mmol, 2.0 equiv), tris(2-phenylpyridyl)iridium 2.62 mg (0.004 mmol, 2.0 mmol%) was placed in a dry Schlenk tube and purged with argon three times. 2 mL of deuteriomethanol was injected into the Schlenk tube with a syringe. The reaction was carried out at 25 °C under irradiation with a blue LED light source (50 W, 455 nm) for 12 h. After the reaction was completed, TLC detection was performed, and the reaction solution was extracted with ethyl acetate and saturated brine (3 x 25 mL), and the organic layer was combined, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The final product (Z)-3-(benzothiazol-2-ylamino)-1-(3,4,5-trimethoxyphenyl)pent-2-en-1-one-5,5,5-d3 47.7 mg was obtained by silica gel column chromatography (petroleum ether: ethyl acetate = 10:1) with a yield of 59%. The characterization data are as follows Figure 9 、 Figure 10 1 H NMR (400 MHz, CDC13) δ 13.90 (s, 1H), 7.79 - 7.71 (m, 2H), 7.40 (t, J = 7.6 Hz, 1H), 7.28 - 7.21 (m, 3H), 6.07 (s, 1H), 3.97 - 3.92 (m, 9H), 3.15 (s, 2H). 13 C NMR (100 MHz, CDC13) δ 189.9, 164.5, 159.3, 153.1, 152.0, 141.8, 134.4, 132.0, 126.2, 124.0, 121.5, 121.0, 105.0, 96.7, 61.0, 56.3, 27.6. HRMS (ESI) m / z: calcd for C 21 H 20 D3N2O4S [M+H] + : 402.1561, found: 402.1612.

[0116] Example 7

[0117]

[0118] ​A mixture of 3-azido-1-(benzothiazol-2-yl)-1-(2,5-dichlorophenyl)but-3-en-1-ol 78.3 mg (0.2 mmol, 1.0 equiv), 5-(deuteriomethyl)5H-thianthrene-5-triflate 153.4 mg (0.4 mmol, 2.0 equiv), sodium carbonate 42.3 mg (0.4 mmol, 2.0 equiv), tris(2-phenylpyridyl)iridium 2.62 mg (0.004 mmol, 2.0 mmol%) was placed in a dry Schlenk tube and purged with argon three times. 2 mL of deuteriomethanol was injected into the Schlenk tube with a syringe. The reaction was carried out at 25 °C under irradiation with a blue LED light source (50 W, 455 nm) for 12 h. After the reaction was completed, TLC detection was performed, and the reaction solution was extracted with ethyl acetate and saturated brine (3 x 25 mL), and the organic layer was combined, dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The final product (Z)-3-(benzothiazol-2-ylamino)-1-(2,5-dichlorophenyl)pent-2-en-1-one-5,5,5-d3 37.7 mg was obtained by silica gel column chromatography (petroleum ether: ethyl acetate = 10:1) with a yield of 50%. The characterization data are as follows Figure 11 、 Figure 12 1 H NMR (400 MHz, CDCl3) δ 13.50 (s, 1H), 7.81-7.72 (m, 2H), 7.51 (d, J = 2.0 Hz, 1H), 7.42 (t, J = 7.6 Hz, 1H), 7.36-7.26 (m, 3H), 5.81 (s, 1H), 3.12 (s, 2H). 13 C NMR (100 MHz, CDCl3) δ 190.5, 165.5, 159.0, 151.8, 141.4, 132.9, 132.1, 131.6, 130.9, 129.4, 129.3, 126.4, 124.3, 121.7, 121.1, 100.5, 27.4. HRMS (ESI) m / z: calcd for C 18 H 11 D3Cl2N2OSNa[M+Na] + :402.0284, found:402.0280.

[0119] Example 8

[0120]

[0121] ​Take 3-azido-1-(benzothiazol-2-yl)-1-(naphthalen-2-yl)but-3-en-1-ol 54.6 mg (0.2 mmol, 1.0 equiv), 5-(deuteriomethyl)5H-thianthrene-5-trifluoromethanesulfonate 153.4 mg (0.4 mmol, 2.0 equiv), sodium carbonate 42.3 mg (0.4 mmol, 2.0 equiv), tris(2-phenylpyridyl)iridium 2.62 mg (0.004 mmol, 2.0 mmol%) into a dry Schlenk reaction tube, replace argon three times; inject 2 mL of deuteriomethanol into the Schlenk reaction tube with a syringe. Irradiate with a blue LED light source (50 W, 455 nm), and carry out the reaction at 25 °C, reaction time 12 h. After the reaction is completed, carry out TLC detection, extract the reaction solution with ethyl acetate and saturated brine (3 x 25 mL), combine the organic layers, dry with anhydrous sodium sulfate, remove the solvent by distillation under reduced pressure, and then purify by silica gel column chromatography (petroleum ether: ethyl acetate = 10:1) to obtain the final product (Z)-3-(benzothiazol-2-ylamino)-1-(naphthalen-2-yl)pent-2-en-1-one-5,5,5-d3 40.2 mg, yield 55%. The characterization data are as follows Figure 13 、 Figure 14 , 1 H NMR (400 MHz, CDCl3) δ 13.94 (s, 1H), 8.38 (s, 1H), 7.98-7.94 (m, 1H), 7.89 (d, J = 7.5 Hz, 1H), 7.85-7.78 (m, 2H), 7.71-7.63 (m, 2H), 7.51-7.44 (m, 2H), 7.34-7.30 (m, 1H), 7.21-7.17 (m, 1H), 6.22 (s, 1H), 3.10 (s, 2H). 13 C NMR (100 MHz, CDCl3) δ 190.7, 164.6, 159.4, 152.0, 136.4, 135.2, 132.8, 132.0, 129.5, 128.5, 128.4, 128.0, 127.8, 126.6, 126.2, 124.0, 123.9, 121.5, 121.1, 97.1, 27.6. HRMS (ESI) m / z: calcd for C 22 H 15 D3N2OSNa[M+Na] + : 384.1220, found: 384.1211.

[0122] Example 9

[0123]

[0124] A mixture of 3-azido-1-(benzothiazol-2-yl)-1-(6-chloropyridin-3-yl)but-3-en-1-ol 71.6 mg (0.2 mmol, 1.0 equiv), 5-(deuteriomethyl)5H-thianthrene-5-trifluoromethanesulfonate 153.4 mg (0.4 mmol, 2.0 equiv), sodium carbonate 42.3 mg (0.4 mmol, 2.0 equiv), tris(2-phenylpyridyl)iridium 2.62 mg (0.004 mmol, 2.0 mmol%) was added into a dry Schlenk tube, which was purged with argon for three times; 2 mL of deuteriomethanol was injected into the Schlenk tube by a syringe. The reaction was carried out at 25 °C under irradiation with a blue LED light source (50 W, 455 nm) for 12 h. After the reaction was completed, TLC detection was carried out, and the reaction solution was extracted with ethyl acetate and saturated brine (3 x 25 mL), and the organic layer was combined and dried over anhydrous sodium sulfate. After the solvent was removed by distillation under reduced pressure, the final product (Z)-3-(benzothiazol-2-ylamino)-1-(6-chloropyridin-3-yl)pent-2-en-1-one-5,5,5-d3 41.7 mg was obtained by silica gel column chromatography (petroleum ether: ethyl acetate = 10:1) with a yield of 60%. The characterization data are as follows: Figure 15 、 Figure 16 , 1 H NMR (400 MHz, CDCl3) δ 13.75 (s, 1H), 8.83 (d, J = 2.1 Hz, 1H), 8.15-8.06 (m, 1H), 7.74-7.61 (m, 2H), 7.39-7.30 (m, 2H), 7.23-7.18 (m, 1H), 5.95 (s, 1H), 3.06 (s, 2H). 13 C NMR (100 MHz, CDCl3) δ 187.2, 166.4, 158.8, 154.4, 151.8, 149.0, 137.7, 133.2, 132.1, 126.4, 124.3, 121.8, 121.1, 96.2, 27.6. HRMS (ESI) m / z: calcd for C 17 H 11 D3ClN3OSNa[M+Na] + : 369.0627, found: 369.0623.

[0125] Example 10

[0126]

[0127] A mixture of 3-azido-1-(4-methylbenzo[d]thiazol-2-yl)-1-phenyl-3-buten-1-ol 67.3 mg (0.2 mmol, 1.0 equiv), 5-(deuteriomethyl)5H-thianthrene-5-trifluoromethanesulfonate 153.4 mg (0.4 mmol, 2.0 equiv), sodium carbonate 42.3 mg (0.4 mmol, 2.0 equiv), tris(2-phenylpyridyl)iridium 2.62 mg (0.004 mmol, 2.0 mmol%) was placed in a dry Schlenk tube and purged with argon three times. 2 mL of deuteriomethanol was injected into the Schlenk tube with a syringe. The reaction was carried out at 25 °C under irradiation with a blue LED light source (50 W, 455 nm) for 12 h. After the reaction was completed, TLC detection was performed, and the reaction solution was extracted with ethyl acetate and saturated brine (3 x 25 mL). The combined organic layers were dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The final product (Z)-3-((4-methylbenzo[d]thiazol-2-yl)amino)-1-phenyl-2-penten-1-one-5,5,5-d3 46.1 mg was obtained by silica gel column chromatography (petroleum ether: ethyl acetate = 10:1) with a yield of 70%. The characterization data are as follows Figure 17 , Figure 18 : 1 H NMR (400 MHz, CDCl3) δ 13.83 (s, 1H), 7.88-7.83 (m, 2H), 7.46-7.34 (m, 4H), 7.12-7.03 (m, 2H), 6.03 (s, 1H), 3.03 (s, 2H), 2.53 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 190.8, 164.7, 158.1, 151.2, 139.1, 132.0, 131.8, 131.4, 128.6, 127.5, 126.9, 123.9, 118.4, 96.9, 27.8, 18.3. HRMS (ESI) m / z: calcd for C 19 H 15 D3N2OSNa[M+Na] + : 348.1220, found: 348.1221.

[0128] Example 11

[0129]

[0130] Successively take 3-azido-1-(4,5-dimethylthiazol-2-yl)-1-phenyl-3-buten-1-ol 60.1 mg (0.2 mmol, 1.0 equiv), 5-(deuterated methyl)5H-thianthrene-5-triflate 153.4 mg (0.4 mmol, 2.0 equiv), sodium carbonate 42.3 mg (0.4 mmol, 2.0 equiv), tris(2-phenylpyridyl)iridium 2.62 mg (0.004 mmol, 2.0 mmol%) into a dry Schlenk reaction tube, replace argon for three times; inject 2 mL of deuterated methanol into the Schlenk reaction tube with a syringe. Irradiate with a blue LED light source (50 W, 455 nm), and carry out the reaction at 25 °C, the reaction time is 12 h. After the reaction is completed, carry out TLC detection, extract the reaction solution with ethyl acetate and saturated brine (3 × 25 mL), dry the combined organic layer with anhydrous sodium sulfate, remove the solvent by distillation under reduced pressure, and then purify by silica gel column chromatography (petroleum ether: ethyl acetate = 10:1) to obtain the final product (Z)-3-((4,5-dimethylthiazol-2-yl)amino)-1-phenyl-2-penten-1-one-5,5,5-d3 37.4 mg, the yield is 64%. The characterization data are as follows Figure 19 、 Figure 20 1 H NMR (400 MHz, CDCl3) δ 13.60 (s, 1H), 7.84 (d, J = 7.0 Hz, 2H), 7.44-7.33 (m, 3H), 5.93 (s, 1H), 2.81 (s, 2H), 2.21 (s, 3H), 2.16 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 190.0, 165.0, 155.9, 145.2, 139.5, 131.5, 128.4, 127.3, 120.9, 94.8, 26.8, 14.8, 11.1. HRMS (ESI) m / z: calcd for C 16 H 15 D3N2OSNa[M+Na] + : 312.1220, found: 312.1225.

[0131] Example 12

[0132]

[0133] ​Successively take 3-azido-1-(6-(2-morpholino-2-oxoethoxy)benzothiazol-2-yl)-1- phenyl-3-buten-1-ol 93.1 mg (0.2 mmol, 1.0 equiv), 5-(deuteriomethyl)5H-thianthrene-5- triflate 153.4 mg (0.4 mmol, 2.0 equiv), sodium carbonate 42.3 mg (0.4 mmol, 2.0 equiv), tris(2-phenylpyridyl)iridium 2.62 mg (0.004 mmol, 2.0 mmol%) into a dry Schlenk reaction tube, replace argon three times; inject 2 mL of deuteriomethanol into the Schlenk reaction tube with a syringe. Irradiate with a blue LED light source (50 W, 455 nm), and carry out the reaction at 25 °C, reaction time 12 h. After the reaction is completed, carry out TLC detection, extract the reaction solution with ethyl acetate and saturated brine (3 x 25 mL), combine the organic layers, dry with anhydrous sodium sulfate, remove the solvent by distillation under reduced pressure, and then purify by silica gel column chromatography (petroleum ether: ethyl acetate = 10:1) to obtain the final product (Z)-3-((6-(2-morpholino-2-oxoethoxy)benzothiazol-2-yl)amino)-1-phenyl-2-penten-1-one-5,5,5-d3 57.4 mg, yield 63%. Characterization data are as follows Figure 21 、 Figure 22 indicated): 1 H NMR (400 MHz, CDCl3) δ 13.90 (s, 1H), 7.98-7.92 (m, 2H), 7.67 (d, J = 8.9 Hz, 1H), 7.55-7.45 (m, 3H), 7.30 (d, J = 2.6 Hz, 1H), 7.07-7.01 (m, 1H), 6.13 (s, 1H), 4.74 (s, 2H), 3.69-3.61 (m, 8H), 3.11 (s, 2H). 13 C NMR (100 MHz, CDCl3) δ 190.8, 166.5, 164.6, 157.9, 154.9, 147.0, 139.1, 133.3, 132.0, 128.5, 127.5, 122.2, 115.0, 105.8, 96.6, 68.3, 66.8, 46.0, 42.5, 27.5. HRMS (ESI) m / z: calcd for C 24 H 22 D3N3O4SNa [M+Na] + : 477.1646, found: 477.1641.

[0134] Example 13

[0135]

[0136] A solution of 3-azido-1-(benzoxazol-2-yl)-1-phenyl-3-buten-1-ol 61.3 mg (0.2 mmol, 1.0 equiv), 5-(deuteriomethyl)5H-thianthrene-5-trifluoromethanesulfonate 153.4 mg (0.4 mmol, 2.0 equiv), sodium carbonate 42.3 mg (0.4 mmol, 2.0 equiv), tris(2-phenylpyridyl)iridium 2.62 mg (0.004 mmol, 2.0 mmol%) was taken into a dry Schlenk reaction tube, which was replaced with argon three times; 2 mL of deuteriomethanol was injected into the Schlenk reaction tube with a syringe. The reaction was carried out at 25 °C under irradiation with a blue LED light source (50 W, 455 nm) for 12 h. After the reaction was completed, TLC detection was performed, and the reaction solution was extracted with ethyl acetate and saturated brine (3 x 25 mL), and the organic layer was combined, dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The final product (Z)-3-(benzoxazol-2-ylamino)-1-phenyl-2-penten-1-one-5,5,5-d3 34.1 mg was obtained by silica gel column chromatography (petroleum ether: ethyl acetate = 10:1) with a yield of 58%. The characterization data are as follows (Fig. 1): Figure 23 、 Figure 24 1 H NMR (400 MHz, CDCl3) δ 13.73 (s, 1H), 7.89 (d, J = 7.3 Hz, 2H), 7.49-7.44 (m, 2H), 7.42-7.37 (m, 2H), 7.32 (d, J = 7.9 Hz, 1H), 7.20-7.16 (m, 1H), 7.15-7.11 (m, 1H), 6.14 (s, 1H), 3.05 (s, 2H). 13 C NMR (100 MHz, CDCl3) δ 191.2, 162.7, 155.7, 147.9, 142.3, 138.9, 132.2, 128.6, 127.6, 124.4, 123.3, 118.3, 109.6, 97.6, 27.1. HRMS (ESI) m / z: calcd for C 18 H 14 D3N2O2[M+H] + : 296.1473, found: 296.1485.

[0137] Example 14

[0138]

[0139] ​Successively take 3-azido-1-(benzothiazol-2-yl)-1-phenyl-3-buten-1-ol 64.5 mg (0.2 mmol, 1.0 equiv), 5-(deuterated methyl)5H-thianthrene-5-triflate 153.4 mg (0.4 mmol, 2.0 equiv), potassium phosphate dibasic 69.7 mg (0.4 mmol, 2.0 equiv), tris[2-(2,4-difluorophenyl)pyridine]iridium(III) 3.05 mg (0.004 mmol, 2.0 mmol%) into a dry Schlenk reaction tube, replace argon for three times; inject 2 mL of acetone into the Schlenk reaction tube with a syringe. Irradiate with a blue LED light source (50 W, 455 nm), and carry out the reaction at 25°C, and the reaction time is 12 h. After the reaction is completed, carry out TLC detection, extract the reaction solution with ethyl acetate and saturated brine (3×25 mL), dry the combined organic layer with anhydrous sodium sulfate, remove the solvent by distillation under reduced pressure, and then carry out column chromatography on silica gel (petroleum ether: ethyl acetate = 10:1) to obtain the final product (Z)-3-(benzothiazol-2-ylamino)-1-phenyl-2-penten-1-one-5,5,5-d3 31.1 mg, the yield is 50%.

[0140] The present application provides a kind of methylene amine ketone compound containing deuterium and its preparation method, and method and approach of many specific implementation of the technical scheme, above-mentioned only preferred embodiment of the present application, it should be pointed out, for the ordinary skilled person in the art, without departing from the principles of the present application, can also make several improvements and refinements, these improvements and refinements also should be considered as the protection scope of the present application. Each component not explicitly described in the embodiment can be realized by prior art.

Claims

1. A method for preparing a deuterated methylenamine ketone compound, characterized in that, A homogeneous solution was prepared by mixing a 3-azido-modified allyl alcohol derivative 1 with 5-(deuterated methyl)5H-thiaanthracene-5-trifluoromethanesulfonate 2, a photocatalyst, a base, and a solvent. The homogeneous solution was then placed in a reaction tube equipped with a light source to carry out the reaction, thereby obtaining a deuterated methyl enamine ketone compound 3. The structural formula of the 3-azido-homallyl alcohol derivative 1 is shown in Formula 1, the structural formula of 5-(deuterated methyl)5H-thiaanthracene-5-trifluoromethanesulfonate 2 is shown in Formula 2, and the structural formula of the deuterated methyl enamino ketone compound 3 is shown in Formula 3. Among them, R 1 The substituted or unsubstituted phenyl, unsubstituted naphthyl, or substituted pyridyl; wherein the substituted substituted substituted substituted by one or more of the same or different groups; the substituted substituted substituted substituted substituted by any one or more of chlorine, bromine, phenyl, cyano, and C1-C2 alkoxy groups; R 2 Selected from substituted or unsubstituted benzothiazolyl, substituted thiazolyl, or benzoxazolyl; wherein the substitution is performed by one or more identical or different groups; the substitution is selected from oxoC1-C2 alkoxy groups substituted with C1-C2 alkyl or morpholinoyl groups; The photocatalyst is tris[2-(2,4-difluorophenyl)pyridine]iridium(III) or tris(2-phenylpyridinyl)iridium; The alkali is sodium carbonate or dipotassium hydrogen phosphate; The solvent is deuterated methanol or acetone.

2. The preparation method according to claim 1, characterized in that, R 1 The substituted group is selected from substituted phenyl, phenyl, naphthyl, or substituted pyridyl; wherein the substituted group is substituted by one or more of the same or different groups; the substituted group is selected from any one or more of chlorine, bromine, phenyl, cyano, and methoxy groups; R 2 The group is selected from substituted or unsubstituted benzothiazolyl, substituted thiazolyl, or benzoxazolyl; wherein the substitution is performed by one or more identical or different groups; and the substitution is selected from oxoethoxy groups substituted with methyl or morpholinoyl.

3. The preparation method according to claim 1, characterized in that, The 3-azido-containing homoallylic alcohol derivative 1 is selected from one of the following structures:

4. The preparation method according to claim 1, characterized in that, The molar ratio of the 3-azido-homallyl alcohol derivative 1, 5-(deuterated methyl)5H-thiaanthracene-5-trifluoromethanesulfonate 2, photocatalyst, and base is 1:1-5:0.01-0.03:1-2; the concentration of the 3-azido-homallyl alcohol derivative 1 in the homogeneous solution is 0.05-1.00 mmol / mL.

5. The preparation method according to claim 1, characterized in that, The homogeneous solution is placed in a reaction tube equipped with a blue LED light source, which is a light strip or bulb with a power of 5-60W and a wavelength of 400-760nm.

6. The preparation method according to claim 1, characterized in that, The reaction is carried out under the protection of an inert gas.

7. The preparation method according to claim 1, characterized in that, The reaction is carried out at a temperature of 20–30°C for 10–14 hours.

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