Deuterium-labeled alkylating agents, methods of synthesis and use thereof

Abstract

The application discloses a deuterium-carrying alkyl reagent and a synthesis method and application thereof. A structural formula of the deuterium-carrying alkyl reagent is shown in formula I or formula II. The deuterium-carrying alkyl reagent is prepared by using alkyl triphenyl phosphonium iodide as a raw material and carrying out hydrogen-deuterium exchange in deuterium water through heating. The method is simple in process, high in yield and capable of preparing the deuterium-carrying alkyl reagent in a large amount of ten grams. More importantly, the deuterium-carrying alkyl reagent can be applied to a free radical addition reaction as a free radical reagent, and different kinds of deuterium-carrying alkylated products can be prepared, so that the deuterium-carrying alkyl reagent has important application value.

Description

Technical Field

[0001] This invention belongs to the field of important organic chemical reagent synthesis and application, specifically involving deuterated alkyl reagents and their synthesis methods and applications. Background Technology

[0002] Deuterium substitution has long been a sought-after area in medical science because replacing hydrogen with deuterium can alter pharmacokinetic properties and metabolic stability, potentially enhancing therapeutic efficacy and reducing toxicity. Furthermore, deuterium compounds are widely used in reaction mechanism studies, structural determination, drug metabolism analysis, and the improvement of organic light-emitting diode (OLED) performance. Therefore, developing effective deuterated alkyl reagents and selectively attaching different deuterated alkyl groups into compounds will greatly accelerate the discovery and development of deuterium functional molecules across various fields.

[0003] Despite the development of various deuteration conversion methods, achieving high deuterium content and excellent regioselectivity in alkyl chains remains challenging. Transition metal-catalyzed direct hydrogen isotope exchange (HIE) reactions have been developed in aromatic C(sp...) groups. 2 The HIE (H-H bond) is well established in deuterium-labeled structures (Angew. Chem. Int. Ed. 2018, 57, 3022-3047). However, direct HIE on aliphatic substrates remains underdeveloped and is generally limited to α-oxygen, α-thio, α-amino, benzyl, and acidic C(sp) groups. 3 )-H bonds. Photoredox catalysis has been used in these C(sp) bonds. 3 Direct HIE is performed on the α-H bond. For example, MacMillan and his collaborators demonstrated methods for the α-deuteration and tritritation of complex drugs using photocatalysts and hydrogen atom transfer catalysts (Science 2017, 358, 1182-1187). Despite these advances, these deuteration schemes are generally applicable to hydrogenated or acidic C(sp) bonds. 3 The α-H bond is difficult to address in terms of deuterium content and regioselectivity. Radical defunctionalization-deuteration can regioselectively install a deuterium atom (d1), but this method is limited by the lack of methods to selectively install a leaving group onto the alkyl moiety.

[0004] Significant efforts have been made to promote the development of diverse deuterium drugs by discovering stable, cost-effective, and readily available deuterated reagents. However, most research has focused on d3-methylating agents, such as CD3I, (CD3)2SO, (CD3)2SO4, CD3OD, 5-(d3-methyl)dibenzothiophene salts, cyclic sulfoxides, etc. (Chem. Eur. J. 2021, 27, 11751-11772; Chem. Soc. Rev. 2021, 50, 10806-10835). Recently, Sawama and colleagues developed an electrophilic deuterated alkylating agent ((d3-methyl)dibenzothiophene salts, 5- ... n (-alkyl)-diphenyl sulfide), used to introduce a deuterium atom at the α-position of a heteroatom (Angew. Chem. Int. Ed. 2023, 62, e202311058). However, due to steric hindrance, based on S N The two-step process may struggle to mount sterically hindered d1-alkylating groups. Furthermore, the introduction of deuterium into the alkyl chain remains challenging due to the lack of readily available carbon nucleophiles. Compared to ionic reactions, radical reactions offer several advantages: they are relatively insensitive to steric hindrance, highly compatible with a wide range of functional groups, and achieve various carbon-carbon bond formation through radical addition with multiple unsaturated bonds. Therefore, an ideal solution to overcome the limitations of ionic processes is to use radical deuterated alkylating agents, but such agents have been rarely explored. Recently, the research group of Lu, Shi, et al., developed d1-alkylating agents... 2,3 alkyl sulfides can be used as d-alkyl sulfides in transition metals, photocatalysts, or under metal-free conditions. 2,3 -Alkyl radical precursors are used for C-C bond formation (Angew. Chem. Int. Ed. 2024, e202409862; Nat. Commun. 2024, 15, 5067.). Despite these advances, a significant challenge remains: the difficulty in achieving the introduction of d1 within the alkyl chain, as current strategies do not allow for the synthesis of d1-alkylating agents under their conditions. Given the important applications of deuterated alkyl reagents, the development of novel and efficient deuterated alkyl reagents and their application in the synthesis of bioactive compounds is a highly challenging and significant research area. Summary of the Invention

[0005] To further promote the development of deuterated alkylating agents and provide more usable reagents and methods for organic synthesis and new drug development, the present invention aims to provide a deuterated alkylating agent and its synthesis method and application. The synthesis method of the deuterated alkylating agent is simple and can be applied to the preparation of different types of trifluoromethylated products in free radical deuterated alkylation reactions.

[0006] In a first aspect, the present invention provides a compound represented by Formula I or Formula II (i.e., deuterated alkyltriphenylphosphine iodide).

[0007]

[0008] In Equations I-II, R 1 R 2 Each is independently selected from hydrogen, C1-C7 alkyl, phenyl, benzyl, alkenyl, or trifluoromethyl-substituted alkyl; or, R 1 R 2 It forms C3-C8 cycloalkyl groups with carbons in the main chain;

[0009] R 3 It is selected from C1-C7 alkyl, C3-C8 cycloalkyl, phenyl, phenyl-substituted alkyl, benzyl, alkenyl, alkenyl-substituted alkyl or trifluoromethyl-substituted alkyl.

[0010] In the compounds, the C1-C7 alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, sec-pentyl, n-hexyl, and n-heptyl; the C3-C8 cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl.

[0011] The alkyl group in the phenyl-substituted alkyl group is preferably a C1-C3 alkyl group, including but not limited to methyl and ethyl;

[0012] The alkyl group in the alkenyl-substituted alkyl group is preferably a C1-C3 alkyl group, including but not limited to methyl and ethyl;

[0013] The alkyl group in the trifluoromethyl-substituted alkyl group is preferably a C1-C3 alkyl group, including but not limited to methyl and ethyl.

[0014] As an example, the compound represented by Formula I is any of the following:

[0015]

[0016] As an example, the compound represented by Formula II is any one of the following:

[0017]

[0018] In a second aspect, the present invention protects the method for synthesizing the compound shown in Formula I or Formula II (i.e., deuterated alkyl triphenylphosphine iodide), comprising the following steps: under the presence of a base, the compound shown in Formula III or Formula IV is heated in deuterated water to carry out a hydrogen-deuterium exchange reaction to obtain the compound shown in Formula I or Formula II.

[0019]

[0020] In Equations III-IV, R 1 R 2 R 3 The definitions are the same as those in Equations I and II.

[0021] In the above synthesis method, the ratio of the compound shown in Formula III or Formula IV to deuterium water is 1 mmol: 1.0 mL;

[0022] The alkali is triethylamine or potassium carbonate, and the molar ratio of the compound shown in Formula III or Formula IV to triethylamine is 1:(0.2-1), specifically 1:0.2; the molar ratio of the compound shown in Formula III or Formula IV to potassium carbonate is 1:(0.5-2), specifically 1:1;

[0023] The hydrogen-deuterium exchange reaction is carried out at a temperature of 60–110°C for 3–12 hours, such as at 100°C for 6 hours.

[0024] The hydrogen-deuterium exchange reaction is carried out under vacuum conditions.

[0025] The above-described synthesis method further includes the following post-processing steps after the synthesis is completed: cooling the reaction solution, adding water and extracting three times with dichloromethane, drying the organic phase with anhydrous sodium sulfate and concentrating it, adding diethyl ether and filtering to separate it.

[0026] Thirdly, the present invention protects the use of the compounds shown in Formula I or Formula II in the preparation of deuterated alkylated products as free radical deuterated alkylating agents.

[0027] Fourthly, the method for synthesizing the compound of formula VIII or VIII' (i.e., an indole oxide compound having a deuterated alkyl group) according to the present invention includes the following steps:

[0028] Under alkaline conditions, the compound shown in Formula I or Formula II reacts with the compound shown in Formula V in an organic solvent under visible light to give the compound shown in Formula VIII or Formula VIII'.

[0029]

[0030] In equation VIII, R 1 R 2 The definition is the same as formula I;

[0031] In equation VIII', R 3 The definition is the same as in formula II;

[0032] In equations V, VIII, and VIII', R 4 It can be methyl, ethyl, phenyl, or benzyl.

[0033] Specifically, the compound represented by formula V can be the compound represented by formula Va:

[0034]

[0035] In the above synthesis method, the molar ratio of the compound shown in Formula I or Formula II to the compound shown in Formula V can be (1.5 to 3):1, specifically 2:1;

[0036] The molar ratio of the compound shown in Formula I or Formula II to the alkali can be (0.5-3):1, specifically 1:1;

[0037] The base is selected from at least one of tetramethylguanidine (TMG), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,4-diazabicyclo[2.2.2]octane (DABCO), triethylamine (TEA), diethylamine, N,N-diisopropylethylamine (DIPEA), potassium carbonate, cesium carbonate, potassium phosphate, and sodium bicarbonate;

[0038] The organic solvent is selected from at least one of toluene, xylene, chlorobenzene, benzene, dioxane, tetrahydrofuran (THF), diethyl ether, chloroform, dichloromethane (DCM), 1,2-dichloroethane, ethyl acetate (EtOAc), acetone, acetonitrile, N,N-dimethylformamide (DMF), and N,N-dimethylformamide (DMA), such as anhydrous N,N-dimethylacetamide (DMA) and anhydrous toluene in a volume ratio of 1:4;

[0039] The visible light is blue light with a wavelength of 450nm;

[0040] The reaction is carried out at a temperature of 30–40°C for 24–48 hours, or for 36 hours at 35°C.

[0041] In the above synthesis method, after the reaction is complete, the method further includes the following post-processing steps: concentrating the reaction solution and performing column chromatography separation using a silica gel column with ethyl acetate and petroleum ether as eluents.

[0042] Fifthly, the present invention provides a method for synthesizing compounds of formula IX or IX' (i.e., quinazolinone compounds having a deuterated alkyl group), comprising the following steps:

[0043] Under alkaline conditions, the compound shown in Formula I or Formula II reacts with the compound shown in Formula VI in deuterated water and an organic solvent under visible light to obtain the compound shown in Formula IX or Formula IX'.

[0044]

[0045] In the formula VIX, R 1 R 2 The definition is the same as formula I;

[0046] In equation IX, R 3 The definition is the same as in Formula II.

[0047] In the above synthesis method, the molar ratio of the compound shown in Formula I or Formula II to the compound shown in Formula VI can be 1:(1 to 3), specifically 1:2;

[0048] The molar ratio of the compound shown in Formula I or Formula II to the base can be 1:(0.5-3), specifically 1:2;

[0049] The base is selected from at least one of tetramethylguanidine (TMG), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,4-diazabicyclo[2.2.2]octane (DABCO), triethylamine (TEA), diethylamine, N,N-diisopropylethylamine (DIPEA), potassium carbonate, cesium carbonate, potassium phosphate, and sodium bicarbonate;

[0050] The molar ratio of the deuterium water to the compound shown in Formula I or Formula II is (1-6):1, such as 3:1; or, the molar ratio of the deuterium water to the compound shown in Formula VI is (1-6):1, specifically 3:2;

[0051] The organic solvent is selected from at least one of toluene, xylene, chlorobenzene, benzene, dioxane, tetrahydrofuran (THF), diethyl ether, chloroform, dichloromethane (DCM), 1,2-dichloroethane, dimethyl sulfoxide (DMSO), ethyl acetate (EtOAc), acetone, acetonitrile, N,N-dimethylformamide (DMF), and N,N-dimethylformamide (DMA);

[0052] The visible light is blue light with a wavelength of 450nm;

[0053] The reaction is carried out at a temperature of 30–40°C for 24–48 hours, or for 36 hours at 35°C.

[0054] In the above synthesis method, after the reaction is complete, the method further includes the following post-processing steps: concentrating the reaction solution and performing column chromatography separation using a silica gel column with ethyl acetate and petroleum ether as eluents.

[0055] Sixthly, the method for synthesizing the compound represented by formula X or X' (i.e., a phenanthridine compound having a deuterated alkyl group) according to the present invention includes the following steps:

[0056] In the presence of a base, the compound shown in Formula I or Formula II reacts with the compound shown in Formula VII in an organic solvent to give the compound shown in Formula X or Formula X'.

[0057]

[0058] In formula X, R 1 R 2 The definition is the same as formula I;

[0059] In formula X', R 3 The definition is the same as in Formula II.

[0060] In the above synthesis method, the molar ratio of the compound shown in Formula I or Formula II to the compound shown in Formula VII can be 1:(1 to 3), specifically 1:2;

[0061] The molar ratio of the compound shown in Formula I or Formula II to the base can be 1:(1 to 3), specifically 1:2;

[0062] The base is selected from at least one of tetramethylguanidine (TMG), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,4-diazabicyclo[2.2.2]octane (DABCO), triethylamine (TEA), diethylamine, N,N-diisopropylethylamine (DIPEA), potassium carbonate, cesium carbonate, potassium phosphate, and sodium bicarbonate;

[0063] The organic solvent is selected from at least one of toluene, xylene, chlorobenzene, benzene, dioxane, tetrahydrofuran (THF), diethyl ether, chloroform, dichloromethane (DCM), 1,2-dichloroethane, dimethyl sulfoxide (DMSO), ethyl acetate (EtOAc), acetone, acetonitrile, N,N-dimethylformamide (DMF), and N,N-dimethylformamide (DMA);

[0064] The visible light is blue light with a wavelength of 450nm;

[0065] The reaction is carried out at a temperature of 30–40°C for 24–48 hours, or for 36 hours at 35°C.

[0066] In the above synthesis method, after the reaction is complete, the method further includes the following post-processing steps: concentrating the reaction solution and performing column chromatography separation using a silica gel column with ethyl acetate and petroleum ether as eluents.

[0067] The present invention has the following beneficial effects:

[0068] This invention uses alkyltriphenylphosphine iodide as a raw material and prepares a deuterated alkylating agent by hydrogen-deuterium exchange in deuterated water under the presence of a base and heating. This method is simple, has a high yield, and can be prepared in large quantities at the 10-gram level. More importantly, this deuterated alkylating agent can be used as a free radical reagent in free radical addition reactions to prepare different types of deuterated alkylated products, thus possessing significant application value. Attached Figure Description

[0069] Figure 1 The compound shown in Formula VIII-1 in Example 16 of this invention. 1 H NMR spectrum.

[0070] Figure 2 The compound shown in Formula VIII-1 in Example 16 of this invention. 13 C NMR spectrum. Detailed Implementation

[0071] The present invention will now be described in further detail with reference to specific embodiments. The given embodiments are merely illustrative of the invention and not intended to limit its scope. The embodiments provided below can serve as a guide for further improvements by those skilled in the art and do not constitute a limitation on the invention in any way.

[0072] Unless otherwise specified, the methods used in the following examples are conventional methods, performed according to the techniques or conditions described in the literature in this field or according to the product instructions. Unless otherwise specified, the materials and reagents used in the following examples are commercially available. Nuclear magnetic resonance (NMR) measurements were performed using a Bruker NMR spectrometer. The abbreviations are well-known to those skilled in the art as representing the following functional groups: Me-methyl; Ph-phenyl; CF3-trifluoromethyl.

[0073] Example 1: Synthesis of the compound shown in I-1

[0074] A pre-dried 10 mL pressure-resistant reaction tube was cooled to room temperature under vacuum. Isopropyltriphenylphosphine iodide (1 mmol, 1.0 equiv.), potassium carbonate (1 mmol, 1 equiv.), and 1.0 mL of deuterium water were then added. The mixture was stirred at 100 °C for 6 hours. The reaction solution was cooled, water was added, and the mixture was extracted three times with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and concentrated. After adding diethyl ether, the mixture was filtered to obtain the compound shown in I-1.

[0075]

[0076] The experimental data for the compound shown in Formula I-1 are as follows: White solid. Yield: 0.72 mmol, 311.8 mg, 72%. 1 H NMR (400MHz, Chloroform-d) δ8.02-7.92(m,6H),7.81-7.75(m,3H),7.74-7.67(m,6H),1.36(s,3H),1.31(s,3H). 13 C NMR (151MHz, Chloroform-d) δ 134.9 (d, J = 2.9Hz), 134.1 (d, J = 9.3Hz), 130.6 (d, J = 12.1Hz), 117.8 (d, J = 83.3Hz), 16.3. 31P NMR(162MHz,Chloroform-d)δ32.59.IR(ATR):2987,2901,2154,2009,1393,1250,1066,737,690cm - 1 .HRMS(ESI):m / z[M] + calcd for C 21 H 21 DP + :306.1516; found:306.1501. It has been verified that the obtained compound is the compound shown in Formula I-1.

[0077] Example 2: Synthesis of the compound shown in I-2

[0078] A pre-dried 10 mL pressure-resistant reaction tube was cooled to room temperature under vacuum. Isobutyltriphenylphosphine iodide (1 mmol, 1.0 equiv.), potassium carbonate (1 mmol, 1 equiv.), and 1.0 mL of deuterium water were then added. The mixture was stirred at 100 °C for 6 hours. The reaction solution was cooled, water was added, and the mixture was extracted three times with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and concentrated. After adding diethyl ether, the mixture was filtered to obtain the compound shown in I-2.

[0079]

[0080] The experimental data for the compound shown in Formula I-2 are as follows: White solid. Yield: 0.61 mmol, 272.7 mg, 61%. 1 H NMR (400MHz, Chloroform-d) δ8.01-7.92(m,6H),7.81-7.68(m,9H),2.07-1.99(m,1H),1.42-1.25(m,6H),1.22-1.11(m,1H). 13 C NMR (151MHz, Chloroform-d) δ 134.9 (d, J = 3.1Hz), 134.1 (d, J = 9.3Hz), 130.7 (d, J = 12.1Hz), 117.8 (d, J = 83.1Hz), 23.7, 12.8, 11.7 (d, J = 15.3Hz). 31 P NMR(162MHz,Chloroform-d)δ31.76.IR(ATR):2973,2902,2177,2048,1434,1066,752,691cm -1 .HRMS(ESI):m / z[M] + calcd for C 22 H23 DP + 320.1673; found: 320.1663. Upon verification, the obtained compound is the compound shown in Formula I-2.

[0081] Example 3: Synthesis of the compound shown in I-3

[0082] A pre-dried 10 mL pressure-resistant reaction tube was cooled to room temperature under vacuum. Cyclopentyltriphenylphosphine iodide (1 mmol, 1.0 equiv.), potassium carbonate (1 mmol, 1 equiv.), and 1.0 mL of deuterium water were then added. The mixture was stirred at 100 °C for 6 hours. The reaction solution was cooled, water was added, and the mixture was extracted three times with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and concentrated. After adding diethyl ether, the mixture was filtered to obtain the compound shown in I-3.

[0083]

[0084] The experimental data for the compound shown in Formula I-3 are as follows: White solid. Yield: 0.71 mmol, 325.9 mg, 71%. 1 H NMR(400MHz,Chloroform-d)δ7.91-7.86(m,6H),7.81-7.76(m,3H),7.72-7.61(m ,6H),2.59-2.50(m,2H),1.94-1.80(m,2H),1.72-1.58(m,2H),1.38-1.25(m,2H). 13 C NMR (151MHz, Chloroform-d) δ 135.0 (d, J = 3.0Hz), 134.1 (d, J = 9.5Hz), 130.6 (d, J = 12.1Hz), 118.9 (d, J = 84.6Hz), 28.2, 26.7 (d, J = 8.8Hz). 31 P NMR(162MHz,Chloroform-d)δ31.87.IR(ATR):2972,2902,2031,1433,1108,723,687cm -1 .HRMS(ESI):m / z[M] + calcd for C 23 H 23 DP + :332.1673; found:332.1664. Upon verification, the obtained compound is the compound shown in Formula I-3.

[0085] Example 4: Synthesis of the compound shown in I-4

[0086] A pre-dried 10 mL pressure-resistant reaction tube was cooled to room temperature under vacuum. Cyclopentyltriphenylphosphine iodide (1 mmol, 1.0 equiv.), potassium carbonate (1 mmol, 1 equiv.), and 1.0 mL of deuterium water were then added. The mixture was stirred at 100 °C for 6 hours. The reaction solution was cooled, water was added, and the mixture was extracted three times with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and concentrated. After adding diethyl ether, the mixture was filtered to obtain the compound shown in I-4.

[0087]

[0088] The experimental data for the compound shown in Formula I-4 are as follows: White solid. Yield: 0.64 mmol, 302.7 mg, 64%. 1 H NMR (600MHz, Chloroform-d) δ8.02-7.96(m,6H),7.79-7.70(m,9H),2.22-2.06(m,4H),1.86-1.74(m,3H),1.12-1.04(m,3H). 13 C NMR (151MHz, Chloroform-d) δ 134.8 (d, J = 3.0Hz), 134.1 (d, J = 9.4Hz), 130.6 (d, J = 12.1Hz), 117.5 (d, J = 83.2Hz), 26.6, 26.5, 25.7, 25.2, 25.1. 31 P NMR(162MHz,Chloroform-d)δ28.56.IR(ATR):2990,1436,1276,1261,1110,750cm -1 .HRMS(ESI):m / z[M] + calcd for C 24 H 25 DP + :346.1829; found:346.1809. Upon verification, the obtained compound is the compound shown in Formula I-4.

[0089] Example 5: Synthesis of the compound shown in II-1

[0090] A pre-dried 10 mL pressure-resistant reaction tube was cooled to room temperature under vacuum. Isobutyltriphenylphosphine iodide (1 mmol, 1.0 equiv.), triethylamine (0.2 mmol, 0.2 equiv.), and 1.0 mL of deuterium water were then added. The mixture was stirred at 100 °C for 6 hours. The reaction solution was cooled, water was added, and the mixture was extracted three times with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and concentrated. After adding diethyl ether, the mixture was filtered to obtain the compound shown in II-1.

[0091]

[0092] The experimental data for the compound shown in Formula II-1 are as follows: White solid. Yield: 0.78 mmol, 349.4 mg, 78%. 1 H NMR (400MHz, Chloroform-d) δ7.91-7.79(m,9H),7.75-7.70(m,6H),2.17-2.07(m,1H),1.08(d,J=6.6Hz,6H). 13 C NMR (151MHz, Chloroform-d) δ 135.2 (d, J = 3.0Hz), 133.8 (d, J = 9.9Hz), 130.7 (d, J = 12.5Hz), 118.7 (d, J = 85.4Hz), 24.6, 24.5, 24.5. 31 P NMR(162MHz,Chloroform-d)δ23.21.IR(ATR):2974,2902,2156,2011,1435,1108,1044,730cm -1 .HRMS(ESI):m / z[M] + calcd for C 22 H 22 D2P + :321.1736; found:321.1721. Upon verification, the obtained compound is the compound shown in Formula II-1.

[0093] Example 6: Synthesis of the compound shown in II-2

[0094] A pre-dried 10 mL pressure-resistant reaction tube was lowered to room temperature under vacuum. Then, n-butyltriphenylphosphine iodide (1 mmol, 1.0 equiv.), potassium carbonate (1 mmol, 1 equiv.), and 1.0 mL of deuterium water were added, and the mixture was stirred at 100 °C for 6 hours. The reaction solution was cooled, water was added, and the mixture was extracted three times with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and concentrated. After adding diethyl ether, the mixture was filtered to obtain the compound shown in II-2.

[0095]

[0096] The experimental data for the compound shown in Formula II-2 are as follows: White solid. Yield: 0.83 mmol, 371.8 mg, 83%. 1H NMR (400MHz, Chloroform-d) δ7.87-7.78(m,9H),7.74-7.70(m,6H),1.73-1.58(m,4H),0.92(t,J=7.2Hz,3H). 13 C NMR(151MHz,Chloroform-d)δ135.2(d,J=3.0Hz),133.9(d,J=10.0Hz),130.7(d ,J=12.5Hz),118.3(d,J=85.8Hz),24.6(d,J=4.6Hz),23.9(d,J=16.3Hz),13.9. 31 P NMR(162MHz,Chloroform-d)δ23.34.IR(ATR):2973,2901,2158,1434,1108,736cm -1 .HRMS(ESI):m / z[M] + calcd for C 22 H 22 D2P + :321.1736; found:321.1720. It has been verified that the obtained compound is the compound shown in Formula II-2.

[0097] Example 7: Synthesis of the compound shown in II-3

[0098] A pre-dried 10 mL pressure-resistant reaction tube was cooled to room temperature under vacuum. Then, isopentyltriphenylphosphine iodide (1 mmol, 1.0 equiv.), potassium carbonate (1 mmol, 1 equiv.), and 1.0 mL of deuterium water were added, and the mixture was stirred at 100 °C for 6 hours. The reaction solution was cooled, water was added, and the mixture was extracted three times with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and concentrated. After adding diethyl ether, the mixture was filtered to obtain the compound shown in II-3.

[0099]

[0100] The experimental data for the compound shown in Formula II-3 are as follows: White solid. Yield: 0.66 mmol, 304.9 mg, 66%. 1 H NMR (400MHz, Chloroform-d) δ7.89-7.80(m,9H),7.76-7.70(m,6H),1.93-1.77(m,1H),1.55-1.41(m,2H),0.98(d,J=6.7Hz,3H),0.82(t,J=7.4Hz,3H). 13C NMR(151MHz,Chloroform-d)δ135.2(d,J=3.2Hz),133.8(d,J=9.8Hz),130.7(d,J= 12.6Hz), 118.8 (d, J = 85.4Hz), 31.1 (d, J = 10.4Hz), 30.4, 20.6 (d, J = 6.8Hz), 11.4. 31 P NMR(162MHz,Chloroform-d)δ23.69.IR(ATR):3006,1435,1276,1261,1110,750cm -1 .HRMS(ESI):m / z[M] + calcd for C 23 H 24 D2P + :335.1892; found:335.1876. Upon verification, the obtained compound is the compound shown in Formula II-3.

[0101] Example 8: Synthesis of the compound shown in II-4

[0102] A pre-dried 10 mL pressure-resistant reaction tube was lowered to room temperature under vacuum. Then, 1 mmol of n-octyltriphenylphosphine iodide (1 mmol, 1.0 equiv.), potassium carbonate (1 mmol, 1 equiv.), and 1.0 mL of deuterium water were added, and the mixture was stirred at 100 °C for 6 hours. The reaction solution was cooled, water was added, and the mixture was extracted three times with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and concentrated. After adding diethyl ether, the mixture was filtered to obtain the compound shown in II-4.

[0103]

[0104] The experimental data for the compound shown in Formula II-4 are as follows: white solid. Yield: 0.66 mmol, 332.6 mg, 66%. 1 H NMR (400MHz, Chloroform-d) δ7.85-7.80(m,8H),7.76-7.70(m,6H),7.54-7.45(m,1H),1.65-1.59(m,4H),1.28-1.16(m,8H),0.84(t,J=7.2Hz,3H). 13C NMR(151MHz,Chloroform-d)δ135.2(d,J=3.0Hz),133.8(d,J=10.0Hz),130.7(d,J=12.5Hz) ,118.2(d,J=86.0Hz),31.8,30.5(d,J=15.5Hz),29.2,28.9,22.6,22.5(d,J=4.6Hz),14.1. 31 PNMR(162MHz,Chloroform-d)δ24.73.IR(ATR):2923,1435,1276,1261,1180,1111,750cm - 1 .HRMS(ESI):m / z[M] + calcd for C 26 H 30 D2P + :377.2362; found:377.2353. Upon verification, the obtained compound is the compound shown in Formula II-4.

[0105] Example 9: Synthesis of the compound shown in II-5

[0106] A pre-dried 10 mL pressure-resistant reaction tube was lowered to room temperature under vacuum. Then, cyclohexylmethyltriphenylphosphine iodide (1 mmol, 1.0 equiv.), potassium carbonate (1 mmol, 1 equiv.), and 1.0 mL of deuterium water were added, and the mixture was stirred at 100 °C for 6 hours. The reaction solution was cooled, water was added, and the mixture was extracted three times with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and concentrated. After adding diethyl ether, the mixture was filtered to obtain the compound shown in II-5.

[0107]

[0108] The experimental data for the compound shown in Formula II-5 are as follows: white solid. Yield: 0.65 mmol, 317.2 mg, 65%. 1 H NMR (400MHz, Chloroform-d) δ7.89-7.78(m,9H),7.74-7.69(m,6H),1.73-1.50(m,6H),1.46-1.33(m,2H),1.21-0.97(m,3H). 13C NMR (151MHz, Chloroform-d) δ 135.2 (d, J = 3.1Hz), 133.7 (d, J = 10.0Hz), 130.6 (d, J = 12.5Hz), 118.9 (d, J = 85.1Hz), 34.7 (d, J = 8.4Hz), 33.5, 26.1, 25.3. 31 P NMR(162MHz,Chloroform-d)δ23.34.IR(ATR):2975,2162,2008,1436,1259,1136,1109,738cm -1 .HRMS(ESI):m / z[M] + calcd for C 25 H 26 D2P + :361.2049; found:361.2036. Upon verification, the obtained compound is the compound shown in Formula II-5.

[0109] Example 10: Synthesis of the compound shown in II-6

[0110] A pre-dried 10 mL pressure-resistant reaction tube was cooled to room temperature under vacuum. Cyclopentylmethyltriphenylphosphine iodide (1 mmol, 1.0 equiv.), triethylamine (0.2 mmol, 0.2 equiv.), and 1.0 mL of deuterium water were then added. The mixture was stirred at 100 °C for 6 hours. The reaction solution was cooled, water was added, and the mixture was extracted three times with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and concentrated. After adding diethyl ether, the mixture was filtered to obtain the compound shown in II-6.

[0111]

[0112] The experimental data for the compound shown in Formula II-6 are as follows: White solid. Yield: 0.71 mmol, 336.5 mg, 71%. 1 H NMR (400MHz, Chloroform-d) δ7.94-7.78(m,9H),7.75-7.1(m,6H),2.16-2.09(m,1H),1.75-1.57(m,4H),1.50-1.34(m,4H). 13 C NMR (151MHz, Chloroform-d) δ 135.2 (d, J = 3.2Hz), 133.9 (d, J = 10.1Hz), 130.6 (d, J = 12.4Hz), 118.7 (d, J = 85.2Hz), 34.6 (d, J = 4.7Hz), 34.4 (d, J = 8.5Hz), 24.7. 31P NMR(162MHz,Chloroform-d)δ23.44.IR(ATR):3006,1434,1275,1261,1107,750cm -1 .HRMS(ESI):m / z[M] + calcd for C 24 H 24 D2P + :347.1892; found:347.1884. Upon verification, the obtained compound is the compound shown in Formula II-6.

[0113] Example 11: Synthesis of the compound shown in II-7

[0114] A pre-dried 10 mL pressure-resistant reaction tube was cooled to room temperature under vacuum. Then, 3,3,3-trifluoropropyltriphenylphosphine iodide (1 mmol, 1.0 equiv.), triethylamine (0.2 mmol, 0.2 equiv.), and 1.0 mL of deuterium water were added, and the mixture was stirred at 100 °C for 6 hours. The reaction solution was cooled, water was added, and the mixture was extracted three times with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and concentrated. After adding diethyl ether, the mixture was filtered to obtain the compound shown in II-7.

[0115]

[0116] The experimental data for the compound shown in Formula II-7 are as follows: White solid. Yield: 0.75 mmol, 366.0 mg, 75%. 1 H NMR (400MHz, Chloroform-d) δ7.92-7.81(m,9H),7.80-7.70(m,6H),2.72-2.55(m,2H). 13 C NMR(151MHz,Chloroform-d)δ135.9(d,J=3.0Hz),133.9(d,J=10.3Hz),131.0(d,J =12.8Hz), 125.5(dd,J=277.7,16.4Hz), 116.7(d,J=87.4Hz), 27.56(q,J=31.7Hz). 31 PNMR(162MHz,Chloroform-d)δ25.09.IR(ATR):2975,2903,2162,2008,1436,1259,1136,1109,738cm -1 .HRMS(ESI):m / z[M] + calcd for C 21 H 17 D2F3P+ :361.1297; found:361.1288. Upon verification, the obtained compound is the compound shown in Formula II-7.

[0117] Example 12: Synthesis of the compound shown in II-8

[0118] A pre-dried 10 mL pressure-resistant reaction tube was cooled to room temperature under vacuum. Then, 3,3,3-trifluorobutyltriphenylphosphine iodide (1 mmol, 1.0 equiv.), triethylamine (0.2 mmol, 0.2 equiv.), and 1.0 mL of deuterium water were added, and the mixture was stirred at 100 °C for 6 hours. The reaction solution was cooled, water was added, and the mixture was extracted three times with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and concentrated. After adding diethyl ether, the mixture was filtered to obtain the compound shown in II-8.

[0119]

[0120] The experimental data for the compound shown in Formula II-8 are as follows: White solid. Yield: 0.71 mmol, 356.4 mg, 71%. 1 H NMR (400MHz, Chloroform-d) δ7.91-7.79(m,9H),7.77-7.68(m,6H),2.76-2.64(m,2H),1.90(q,J=7.6Hz,2H). 13 C NMR (151MHz, Chloroform-d) δ 135.5 (d, J = 3.0Hz), 133.9 (d, J = 10.2Hz), 130.8 (d, J = 12.6Hz), 126.61 (q, J = 276.5Hz), 117.7 (d, J = 86.4Hz), 33.8 (m), 15.9. 31 P NMR(162MHz,Chloroform-d)δ24.73.IR(ATR):2987,2901,2158,1976,1392,1251,1066,740cm -1 .HRMS(ESI):m / z[M] + calcd for C 22 H 19 D2F3P + :375.1453; found:375.1444. Upon verification, the obtained compound is the compound shown in Formula II-8.

[0121] Example 13: Synthesis of the compound shown in II-9

[0122] A pre-dried 10 mL pressure-resistant reaction tube was lowered to room temperature under vacuum. Then, phenylethyltriphenylphosphine iodide (1 mmol, 1.0 equiv.), triethylamine (0.2 mmol, 0.2 equiv.), and 1.0 mL of deuterium water were added, and the mixture was stirred at 100 °C for 6 hours. The reaction solution was cooled, water was added, and the mixture was extracted three times with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and concentrated. After adding diethyl ether, the mixture was filtered to obtain the compound shown in II-9.

[0123]

[0124] The experimental data for the compound shown in Formula II-9 are as follows: White solid. Yield: 0.61 mmol, 302.6 mg, 61%. 1 H NMR (400MHz, Chloroform-d) δ7.86-7.79 (m, 9H), 7.73-7.69 (m, 6H), 7.33-7.14 (m, 5H), 3.05 (d, J = 12.3Hz, 2H). 13 C NMR (151MHz, Chloroform-d) δ 138.1, 135.3 (d, J = 3.0Hz), 133.9 (d, J = 10.1Hz), 130.7 (d, J = 12.6Hz), 129.1, 128.8, 118.0 (d, J = 86.0Hz), 28.2. 31 PNMR(162MHz,Chloroform-d)δ24.51.IR(ATR):2986,2902,2163,2009,1435,1111,734cm - 1 .HRMS(ESI):m / z[M] + calcd for C 26 H 22 D2P + :369.1736; found:369.1726. Upon verification, the obtained compound is the compound shown in Formula II-9.

[0125] Example 14: Synthesis of the compound shown in II-10

[0126] A pre-dried 10 mL pressure-resistant reaction tube was lowered to room temperature under vacuum. Then, phenylpropyltriphenylphosphine iodide (1 mmol, 1.0 equiv.), potassium carbonate (1 mmol, 1 equiv.), and 1.0 mL of deuterium water were added, and the mixture was stirred at 100 °C for 6 hours. The reaction solution was cooled, water was added, and the mixture was extracted three times with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and concentrated. After adding diethyl ether, the mixture was filtered to obtain the compound shown in II-10.

[0127]

[0128] The experimental data for the compound shown in Formula II-10 are as follows: White solid. Yield: 0.73 mmol, 372.3 mg, 73%. 1 H NMR (400MHz, Chloroform-d) δ7.79-7.62(m,15H),7.26-7.16(m,5H),3.01(t,J=7.2Hz,2H),1.98-1.90(m,2H). 13 C NMR (151MHz, Chloroform-d) δ 135.0 (d, J = 3.2Hz), 133.6 (d, J = 10.1Hz), 130.4 (d, J = 12.4Hz), 128.9, 128.5, 126.4, 117.9 (d, J = 84.1Hz), 35.5, 24.3. 31 P NMR(162MHz,Chloroform-d)δ24.84.IR(ATR):3006,1469,1275,1260,1110,750cm -1 .cm -1 .HRMS(ESI):m / z[M] + calcd for C 27 H 24 D2P + :383.1892; found:383.1878. It has been verified that the obtained compound is the compound shown in Formula I-14.

[0129] Example 15: Synthesis of the compound shown in II-11

[0130] A pre-dried 10 mL pressure-resistant reaction tube was cooled to room temperature under vacuum. Then, 1-butenyltriphenylphosphine iodide (1 mmol, 1.0 equiv.), triethylamine (0.2 mmol, 0.2 equiv.), and 1.0 mL of deuterium water were added, and the mixture was stirred at 100 °C for 6 hours. The reaction solution was cooled, water was added, and the mixture was extracted three times with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and concentrated. After adding diethyl ether, the mixture was filtered to obtain the compound shown in II-11.

[0131]

[0132] The experimental data for the compound shown in Formula II-11 are as follows: White solid. Yield: 0.72 mmol, 321.1 mg, 72%. 1H NMR (400MHz, Chloroform-d) δ7.89-7.79(m,9H),7.76-7.71(m,6H),6.07-5.96(m,1H),5.14-4.99(m,2H),2.47-2.43(m,2H). 13 C NMR(151MHz,Chloroform-d)δ135.4(d,J=3.1Hz),134.7(d,J=14.9Hz),133.8(d ,J=9.9Hz),130.7(d,J=12.6Hz),118.0(d,J=85.9Hz),117.8,26.5(d,J=3.6Hz). 31 P NMR(162MHz,Chloroform-d)δ24.62.IR(ATR):2974,2902,2162,2008,1394,1066,738,690cm -1 .HRMS(ESI):m / z[M] + calcd for C 22 H 20 D2P + :319.1579; found:319.1567. It has been verified that the obtained compound is the compound shown in formula II-11.

[0133] Example 16, Synthesis of the compound shown in Formula VIII-1

[0134] The pre-dried reaction tube was cooled to room temperature under vacuum. In a glove box, 0.2 mmol (2.0 equiv.) of deuterium-containing alkylating reagent (the compound of formula I-1 prepared in Example 1), 0.1 mmol (1.0 equiv.) of enamide of formula Va, 0.2 mmol (2.0 equiv.) of tetramethylguanidine, 0.2 mL of anhydrous N,N-dimethylacetamide (DMA) and 0.8 mL of anhydrous toluene were added. The mixture was irradiated under a 450 nm blue lamp and stirred at 35 °C until the enamide disappeared as indicated by thin-layer chromatography (36 hours). The reaction solution was concentrated and separated by column chromatography using a silica gel column with ethyl acetate and petroleum ether as eluents to obtain the compound of formula VIII-1.

[0135]

[0136] The experimental data for the compound shown in Formula VIII-1 are as follows: Yellow oil. Yield: 0.082 mmol, 17.9 mg, 82%. 1H NMR(400MHz,Chloroform-d)δ7.30-7.24(m,1H),7.17(d,J=7.3Hz,1H),7.08-7.05(m,1H),6.85(d,J=7.7 Hz,1H),3.22(s,3H),1.94(d,J=14.0Hz,1H),1.76(d,J=14.0Hz,1H),1.33(s,3H),0.62(d,J=16.7Hz,6H). 13 C NMR(151MHz,Chloroform-d)δ181.2,143.3,134.4,127.7,122.9,122.5,108.1,48.2,46.8,26.3 ,26.3,25.4-25.1(m),24.1,22.8.IR(ATR):2957,1706,1612,1469,1375,1260,1122,1026,751cm -1 .HRMS(ESI):m / z[M+H] + calcd for C 14 H 19 DNO + :219.1602; found:219.1597. 1 The H NMR spectrum can be seen Figure 1 , 13 The C NMR spectrum is shown in Figure 2 The structure was verified to be correct. The obtained compound was verified to be the compound shown in Formula VIII-1.

[0137] Example 17, Synthesis of the compound shown in Formula VIII-2

[0138] The pre-dried reaction tube was cooled to room temperature under vacuum. In a glove box, 0.2 mmol (2.0 equiv.) of deuterium-containing alkylating reagent (the compound of formula I-2 prepared in Example 2), 0.1 mmol (1.0 equiv.) of enamide of formula Va, 0.2 mmol (2.0 equiv.) of tetramethylguanidine, 0.2 mL of anhydrous N,N-dimethylacetamide (DMA) and 0.8 mL of anhydrous toluene were added. The mixture was irradiated under a 450 nm blue lamp and stirred at 35 °C until the enamide disappeared as indicated by thin-layer chromatography (36 hours). The reaction solution was concentrated and separated by column chromatography using a silica gel column with ethyl acetate and petroleum ether as eluents to obtain the compound of formula VIII-2.

[0139]

[0140] The experimental data for the compound shown in Formula VIII-2 are as follows: Yellow oil. Yield: 0.078 mmol, 18.1 mg, 78%, dr = 1:1. 1 H NMR(400MHz,Chloroform-d)(mixture of diastereomers)δ7.30-7.22(m,2H),7.19-7.14(m,2H),7.10-7.03(m,2H),6.86-6.83(m,2H),3.22(s,6H),2.02(d,J=13.9Hz,1H ),1.87-1.84(m,2H),1.65(d,J=13.9Hz,1H),1.40-1.28(m,6H),1.19-0.89(m,4H),0.77-0.66(m,6H),0.59(s,3H),0.48(s,3H). 13 C NMR(151MHz,Chloroform-d)(mixtureof diastereomers)δ181.5,181.1,143.4,143.3,134.8,134.2,127.7,123.0,122.9,122.5,122.4,108.1,108.1,48.3,48.0,45.1,44.5 ,31.4-31.2(m),30.8,30.1,26.3,26.3,25.9,20.3,19.3,11.2,11.0.IR(ATR):2962,1706,1612,1469,1374,1259,1122,1028,750cm -1 .HRMS(ESI):m / z[M+H] + calcd for C 15 H 21 DNO + :233.1759; found:233.1748. It has been verified that the obtained compound is the compound shown in formula VIII-2.

[0141] Example 18, Synthesis of the compound shown in formula VIII-3

[0142] The pre-dried reaction tube was cooled to room temperature under vacuum. In a glove box, 0.2 mmol (2.0 equiv.) of deuterium-containing alkylating reagent (the compound of formula I-3 prepared in Example 3), 0.1 mmol (1.0 equiv.) of enamide of formula Va, 0.2 mmol (2.0 equiv.) of tetramethylguanidine, 0.2 mL of anhydrous N,N-dimethylacetamide (DMA) and 0.8 mL of anhydrous toluene were added. The mixture was irradiated under a 450 nm blue lamp and stirred at 35 °C until the enamide disappeared as indicated by thin-layer chromatography (36 hours). The reaction solution was concentrated and separated by column chromatography using a silica gel column with ethyl acetate and petroleum ether as eluents to obtain the compound of formula VIII-3.

[0143]

[0144] The experimental data for the compound shown in Formula VIII-3 are as follows: Light yellow oil. Yield: 0.078 mmol, 19.0 mg, 78%. 1 H NMR(400MHz,Chloroform-d)δ7.30-7.24(m,1H),7.17(d,J=7.3Hz,1H),7.08-7.04(m,1H),6.84(d,J=7.7Hz,1H),3.22(s,3H),2.06 (d,J=13.7Hz,1H),1.89(d,J=13.7Hz,1H),1.52-1.36(m,3H),1.34(s,3H),1.31-1.18(m,3H),1.06-0.94(m,1H),0.88-0.76(m,1H). 13 C NMR(151MHz,Chloroform-d)δ181.3,143.4,134.6,127.7,123.0,122.4,108.0,48.6,44.5,37.0-36.8 (m),33.8,32.8,26.3,25.4,25.1,25.0.IR(ATR):2947,1706,1612,1469,1375,1254,1121,1027,750cm -1 .HRMS(ESI):m / z[M+H] + calcd for C 16 H 21 DNO + :245.1759; found:245.1750. It has been verified that the obtained compound is the compound shown in formula VIII-3.

[0145] Example 19: Synthesis of the compound shown in VIII-4

[0146] The pre-dried reaction tube was cooled to room temperature under vacuum. In a glove box, 0.2 mmol (2.0 equiv.) of deuterium-containing alkylating reagent (the compound of formula I-4 prepared in Example 4), 0.1 mmol (1.0 equiv.) of enamide of formula Va, 0.2 mmol (2.0 equiv.) of tetramethylguanidine, 0.2 mL of anhydrous N,N-dimethylacetamide (DMA) and 0.8 mL of anhydrous toluene were added. The mixture was irradiated under a 450 nm blue lamp and stirred at 35 °C until the enamide disappeared as indicated by thin-layer chromatography (36 hours). The reaction solution was concentrated and separated by column chromatography using a silica gel column with ethyl acetate and petroleum ether as eluents to obtain the compound of formula VIII-4.

[0147]

[0148] The experimental data for the compound shown in Formula VIII-4 are as follows: Light yellow oil. Yield: 0.080 mmol, 20.7 mg, 80%. 1 H NMR(400MHz,Chloroform-d)δ7.29-7.24(m,1H),7.17-7.15(m,1H),7.08-7.04(m,1H),6.84(d,J=7.7Hz,1H),3.22(s,3H),1.93(dd,J=1 4.0,6.7Hz,1H),1.73(dd,J=14.0,5.3Hz,1H),1.56-1.42(m,3H),1.37-1.33(m,1H),1.31(s,3H),1.24-1.17(m,1H),1.00-0.77(m,5H). 13 C NMR(101MHz,Chloroform-d)δ181.3,143.3,134.6,127.7,122.9,122.5,108.1,48.0,45.6,34.9,34.6,3 4.0(d,J=94.2Hz)33.7,26.4,26.3,26.2,26.2.IR(ATR):2919,1707,1612,1450,1375,1251,1123,741cm -1 .HRMS(ESI):m / z[M+H] + calcd forC 17 H 23 DNO + :259.1915; found:259.1904. It has been verified that the obtained compound is the compound shown in formula VIII-4.

[0149] Example 20: Synthesis of the compound shown in formula VIII'-1

[0150] The pre-dried reaction tube was cooled to room temperature under vacuum. In a glove box, 0.2 mmol (2.0 equiv.) of deuterium-containing alkylating reagent (the compound of formula II-2 prepared in Example 6), 0.1 mmol (1.0 equiv.) of enamide of formula Va, 0.2 mmol (2.0 equiv.) of tetramethylguanidine, 0.2 mL of anhydrous N,N-dimethylacetamide (DMA) and 0.8 mL of anhydrous toluene were added. The mixture was irradiated under a 450 nm blue lamp and stirred at 35 °C until the enamide disappeared as indicated by thin-layer chromatography (36 hours). The reaction solution was concentrated and separated by column chromatography using a silica gel column with ethyl acetate and petroleum ether as eluents to obtain the compound of formula VIII'-1.

[0151]

[0152] The experimental data for the compound shown in Formula VIII'-1 are as follows: Light yellow oil. Yield: 0.090 mmol, 21.0 mg, 90%. 1 H NMR(400MHz,Chloroform-d)δ7.33-7.26(m,1H),7.20(dd,J=7.3,1.6Hz,1H),7.13-7.06(m,1H),6.87(d,J=7.4Hz,1H ),3.24(s,3H),1.89(d,J=12.4Hz,1H),1.73(d,J=12.4Hz,1H),1.37(s,3H),1.23-1.11(m,4H),0.80(t,J=6.8Hz,3H). 13 C NMR(151MHz,Chloroform-d)δ181.1,143.5,134.5,127.7,122.6,122.5,108.0,48.6,38.4, 31.8,26.2,23.9,22.4,14.1.IR(ATR):2924,1704,1612,1469,1375,1276,1123,1031,751cm -1 .HRMS(ESI):m / z[M+H] + calcd for C 15 H 20 D2NO + :234.1821; found:234.1817. It has been verified that the obtained compound is the compound shown in formula VIII'-1.

[0153] Example 21: Synthesis of the compound shown in formula VIII'-2

[0154] The pre-dried reaction tube was cooled to room temperature under vacuum. In a glove box, 0.2 mmol (2.0 equiv.) of deuterium-containing alkylating reagent (the compound of formula II-4 prepared in Example 8), 0.1 mmol (1.0 equiv.) of enamide of formula Va, 0.2 mmol (2.0 equiv.) of tetramethylguanidine, 0.2 mL of anhydrous N,N-dimethylacetamide (DMA) and 0.8 mL of anhydrous toluene were added. The mixture was irradiated under a 450 nm blue lamp and stirred at 35 °C until the enamide disappeared as indicated by thin-layer chromatography (36 hours). The reaction solution was concentrated and separated by column chromatography using a silica gel column with ethyl acetate and petroleum ether as eluents to obtain the compound of formula VIII'-2.

[0155]

[0156] The experimental data for the compound shown in Formula VIII'-2 are as follows: Light yellow oil. Yield: 0.083 mmol, 24.0 mg, 83%. 1 H NMR(400MHz,Chloroform-d)δ7.30-7.23(m,1H),7.17(d,J=7.3Hz,1H),7.09-7.04(m,1H),6.84(d,J=7.7Hz,1H),3 .21(s,3H),1.86(d,J=13.3Hz,1H),1.70(d,J=13.3Hz,1H),1.34(s,3H),1.26-1.09(m,12H),0.85(t,J=7.0Hz,3H). 13 C NMR(151MHz,Chloroform-d)δ181.1,143.5,134.5,127.7,122.6,122.5,108.0,48.6,38.5,31.9,29.7, 29.6,29.4,29.4,26.2,23.9,22.8,14.2.IR(ATR):2921,1710,1613,1469,1375,1276,1123,1032,751cm -1 .HRMS(ESI):m / z[M+H] + calcd for C 19 H 28 D2NO + :290.2447; found:290.2437. It has been verified that the obtained compound is the compound shown in formula VIII'-2.

[0157] Example 22, Synthesis of the compound shown in formula VIII'-3

[0158] The pre-dried reaction tube was cooled to room temperature under vacuum. In a glove box, 0.2 mmol (2.0 equiv.) of deuterium-containing alkylating reagent (the compound shown in Formula I-5 prepared in Example 5), 0.1 mmol (1.0 equiv.) of enamide shown in Formula Va, 0.2 mmol (2.0 equiv.) of tetramethylguanidine, 0.2 mL of anhydrous N,N-dimethylacetamide (DMA) and 0.8 mL of anhydrous toluene were added. The mixture was irradiated under a 450 nm blue lamp and stirred at 35 °C until the enamide disappeared as indicated by thin-layer chromatography (36 hours). The reaction solution was concentrated and separated by column chromatography using a silica gel column with ethyl acetate and petroleum ether as eluents to obtain the compound shown in Formula VIII'-3.

[0159]

[0160] The experimental data for the compound shown in Formula VIII'-3 are as follows: Light yellow oil. Yield: 0.068 mmol, 15.8 mg, 68%. 1 H NMR(600MHz,Chloroform-d)δ7.28-7.25(m,2H),7.17-7.16(m,1H),7.08-7.08(m,1H),6.84(d,J=7.8Hz,1H),3.22(s,3H),1 .87(d,J=13.3Hz,1H),1.72(d,J=13.3Hz,1H),1.41-1.37(m,1H),1.35(s,3H),0.78(d,J=6.6Hz,3H),0.76(d,J=6.6Hz,3H). 13 C NMR(151MHz,Chloroform-d)δ181.0,143.5,134.5,127.7,122.6,122.6,108.0,48.5,36.3, 28.1,26.2,24.0,22.6,22.4.IR(ATR):2955,1706,1612,1468,1376,1275,1124,1031,751cm -1 .HRMS(ESI):m / z[M+H] + calcd for C 15 H 20 D2NO + :234.1821; found:234.1817. It has been verified that the obtained compound is the compound shown in formula VIII'-3.

[0161] Example 23, Synthesis of the compound shown in formula VIII'-4

[0162] The pre-dried reaction tube was cooled to room temperature under vacuum. In a glove box, 0.2 mmol (2.0 equiv.) of deuterium-containing alkylating reagent (the compound of formula II-3 prepared in Example 7), 0.1 mmol (1.0 equiv.) of enamide of formula Va, 0.2 mmol (2.0 equiv.) of tetramethylguanidine, 0.2 mL of anhydrous N,N-dimethylacetamide (DMA) and 0.8 mL of anhydrous toluene were added. The mixture was irradiated under a 450 nm blue lamp and stirred at 35 °C until the enamide disappeared as indicated by thin-layer chromatography (36 hours). The reaction solution was concentrated and separated by column chromatography using a silica gel column with ethyl acetate and petroleum ether as eluents to obtain the compound of formula VIII'-4.

[0163]

[0164] The experimental data for the compound shown in Formula VIII'-4 are as follows: Light yellow oil. Yield: 0.072 mmol, 17.8 mg, 72%, dr = 1:1. 1 H NMR(400MHz,Chloroform-d)(mixture of diastereomers)δ7.29-7.25(m,1H),7.19-7.13(m,1H),7.09-7.05(m,1H),6.84(d,J=7.7Hz,1H),3.22(s,3H) ,1.91-1.82(m,1H),1.77-1.63(m,1H),1.35(s,3H),1.27-1.10(m,2H),1.07-0.94(m,1H),0.81-0.69(m,6H). 13 C NMR(151MHz,Chloroform-d)(mixture of diastereomers)δ181.0,181.0,143.5,134.5,127.7,122.6,122.5,108.0,48.5,35.9,35.8,34.4,34.4,29.2, 28.9,26.2,24.0,24.0,19.1,19.0,11.5,11.3.IR(ATR):2960,1707,1612,1470,1374,1276,1124,1031,751cm -1 .HRMS(ESI):m / z[M+H] + calcd for C 16 H 22 D2NO+ :248.1978; found:248.1973. It has been verified that the obtained compound is the compound shown in formula VIII'-4.

[0165] Example 24: Synthesis of the compound shown in formula VIII'-5

[0166] The pre-dried reaction tube was cooled to room temperature under vacuum. In a glove box, 0.2 mmol (2.0 equiv.) of deuterium-containing alkylating reagent (the compound of formula II-6 prepared in Example 10), 0.1 mmol (1.0 equiv.) of enamide of formula Va, 0.2 mmol (2.0 equiv.) of tetramethylguanidine, 0.2 mL of anhydrous N,N-dimethylacetamide (DMA) and 0.8 mL of anhydrous toluene were added. The mixture was irradiated under a 450 nm blue lamp and stirred at 35 °C until the enamide disappeared as indicated by thin-layer chromatography (36 hours). The reaction solution was concentrated and separated by column chromatography using a silica gel column with ethyl acetate and petroleum ether as eluents to obtain the compound of formula VIII'-5.

[0167]

[0168] The experimental data for the compound shown in Formula VIII'-5 are as follows: Light yellow oil. Yield: 0.081 mmol, 21.0 mg, 81%. 1 H NMR(400MHz,Chloroform-d)δ7.29-7.25(m,1H),7.18-7.15(m,1H),7.09-7.05(m,1H),6.84(d,J=7.7Hz,1H),3 .22(s,3H),1.88(d,J=13.3Hz,1H),1.72(d,J=13.3Hz,1H),1.68-1.40(m,7H),1.35(s,3H),1.31-1.21(m,2H). 13 C NMR(101MHz,Chloroform-d)δ181.0,143.5,134.5,127.7,122.6,108.0,48.6,40.1,37.7,3 2.6,31.7,26.3,25.3,24.8,22.8.IR(ATR):2945,1709,1612,1469,1376,1251,1124,754cm -1 .HRMS(ESI):m / z[M+H] + calcd for C 17 H 22 D2NO +:260.1978; found:260.1962. It has been verified that the obtained compound is the compound shown in formula VIII'-5.

[0169] Example 25: Synthesis of the compound shown in formula VIII'-6

[0170] The pre-dried reaction tube was cooled to room temperature under vacuum. In a glove box, 0.2 mmol (2.0 equiv.) of deuterium-containing alkylating reagent (the compound of formula II-5 prepared in Example 9), 0.1 mmol (1.0 equiv.) of enamide of formula Va, 0.2 mmol (2.0 equiv.) of tetramethylguanidine, 0.2 mL of anhydrous N,N-dimethylacetamide (DMA) and 0.8 mL of anhydrous toluene were added. The mixture was irradiated under a 450 nm blue lamp and stirred at 35 °C until the enamide disappeared as indicated by thin-layer chromatography (36 hours). The reaction solution was concentrated and separated by column chromatography using a silica gel column with ethyl acetate and petroleum ether as eluents to obtain the compound of formula VIII'-6.

[0171]

[0172] The experimental data for the compound shown in Formula VIII'-6 are as follows: Light yellow oil. Yield: 0.078 mmol, 21.3 mg, 78%. 1 H NMR(400MHz,Chloroform-d)δ7.29-7.23(m,1H),7.16-7.14(m,1H),7.08-7.04(m,1H),6.84(d,J=7.8Hz,1H),3.21(s, 3H),1.88(d,J=13.0Hz,1H),1.77-1.69(m,1H),1.62-1.55(m,5H),1.34(s,3H),1.18-1.00(m,4H),0.80-0.66(m,2H). 13 C NMR(101MHz,Chloroform-d)δ181.0,143.5,134.5,127.7,122.6,122.5,108.0,48.5,37.8,35. 9,33.3,26.7,26.4,26.2,24.0.IR(ATR):2919,1707,1612,1450,1376,1246,1121,1020,751cm - 1 .HRMS(ESI):m / z[M+H] + calcd for C 18 H 24 D2NO +:274.2134; found:274.2126. It has been verified that the obtained compound is the compound shown in formula VIII'-6.

[0173] Example 26: Synthesis of the compound shown in formula VIII'-7

[0174] The pre-dried reaction tube was cooled to room temperature under vacuum. In a glove box, 0.2 mmol (2.0 equiv.) of deuterium-containing alkylating reagent (the compound of formula II-11 prepared in Example 15), 0.1 mmol (1.0 equiv.) of enamide of formula Va, 0.2 mmol (2.0 equiv.) of tetramethylguanidine, 0.2 mL of anhydrous N,N-dimethylacetamide (DMA) and 0.8 mL of anhydrous toluene were added. The mixture was irradiated under a 450 nm blue lamp and stirred at 35 °C until the enamide disappeared as indicated by thin-layer chromatography (36 hours). The reaction solution was concentrated and separated by column chromatography using a silica gel column with ethyl acetate and petroleum ether as eluents to obtain the compound of formula V-11.

[0175]

[0176] The experimental data for the compound shown in Formula VIII'-7 are as follows: Light yellow oil. Yield: 0.072 mmol, 16.6 mg, 72%. 1 H NMR(400MHz,Chloroform-d)δ7.30-7.23(m,1H),7.16(d,J=7.4Hz,1H),7.11-7.03(m,1H),6.84(d ,J=7.9Hz,1H),5.71-5.57(m,1H),4.95-4.83(m,2H),3.21(s,3H),2.00-1.61(m,4H),1.35(s,3H). 13 C NMR(151MHz,Chloroform-d)δ180.8,143.4,138.3,134.2,127.7,122.6,122.6,114.8,108.0,48.4,38.0, 33.6,26.2,23.8.IR(ATR):2925,1707,1611,1469,1346,1250,1122,1018,910,752.HRMS(ESI):m / z[M+H] + calcd forC 15 H 18 D2NO + :232.1665; found:232.1658. It has been verified that the obtained compound is the compound shown in formula VIII'-7.

[0177] Example 27: Synthesis of the compound shown in formula VIII'-8

[0178] The pre-dried reaction tube was cooled to room temperature under vacuum. In a glove box, 0.2 mmol (2.0 equiv.) of deuterium-containing alkylating reagent (the compound of formula II-9 prepared in Example 13), 0.1 mmol (1.0 equiv.) of enamide of formula Va, 0.2 mmol (2.0 equiv.) of tetramethylguanidine, 0.2 mL of anhydrous N,N-dimethylacetamide (DMA) and 0.8 mL of anhydrous toluene were added. The mixture was irradiated under a 450 nm blue lamp and stirred at 35 °C until the enamide disappeared as indicated by thin-layer chromatography (36 hours). The reaction solution was concentrated and separated by column chromatography using a silica gel column with ethyl acetate and petroleum ether as eluents to obtain the compound of formula VIII'-8.

[0179]

[0180] The experimental data for the compound shown in Formula VIII'-8 are as follows: Light yellow oil. Yield: 0.091 mmol, 25.6 mg, 91%. 1 H NMR(400MHz,Chloroform-d)δ7.29-7.18(m,3H),7.18-7.10(m,2H),7.09-7.00(m,3H),6.83(dd,J=7.8, 3.2Hz,1H),3.20(s,3H),2.53-2.42(m,2H),1.96(d,J=13.4Hz,1H),1.78(d,J=13.4Hz,1H),1.35(s,3H). 13 C NMR(151MHz,Chloroform-d)δ180.8,143.4,142.1,134.2,128.5,128.4,127.8,125.9,122.6,10 8.1,48.5,38.2,36.0,26.3,24.0.IR(ATR):2923,1705,1611,1492,1375,1251,1123,1031,742cm -1 .HRMS(ESI):m / z[M+H] + calcd for C 19 H 20 D2NO + :282.1821; found:282.1812. It has been verified that the obtained compound is the compound shown in formula VIII'-8.

[0181] Example 28: Synthesis of the compound shown in formula VIII'-9

[0182] The pre-dried reaction tube was cooled to room temperature under vacuum. In a glove box, 0.2 mmol (2.0 equiv.) of deuterium-containing alkylating reagent (the compound of formula II-8 prepared in Example 12), 0.1 mmol (1.0 equiv.) of enamide of formula Va, 0.2 mmol (2.0 equiv.) of tetramethylguanidine, 0.2 mL of anhydrous N,N-dimethylacetamide (DMA) and 0.8 mL of anhydrous toluene were added. The mixture was irradiated under a 450 nm blue lamp and stirred at 35 °C until the enamide disappeared as indicated by thin-layer chromatography (36 hours). The reaction solution was concentrated and separated by column chromatography using a silica gel column with ethyl acetate and petroleum ether as eluents to obtain the compound of formula VIII'-9.

[0183]

[0184] The experimental data for the compound shown in Formula VIII'-9 are as follows: Light yellow oil. Yield: 0.076 mmol, 21.8 mg, 76%. 1 H NMR(400MHz,Chloroform-d)δ7.33-7.24(m,1H),7.17(d,J=7.3Hz,1H),7.12-7.04(m,1H),6 .86(d,J=8.6Hz,1H),3.22(s,3H),1.98-1.86(m,3H),1.78-1.69(m,1H),1.46-1.36(m,5H). 13 C NMR(151MHz,Chloroform-d)δ180.6,143.4,133.9,128.0,127.4(q,J=276.3Hz),122.7,122.5,108.2,48.3,38 .0(t,J=15.1Hz),33.6(m),26.3,23.9,21.9(m).IR(ATR):2933,1708,1613,1470,1377,1256,1136,1017,750cm -1 .HRMS(ESI):m / z[M+H] + calcd for C 15 H 17 D2NOF3 + :288.1539; found:288.1525. It has been verified that the obtained compound is the compound shown in formula VIII'-9.

[0185] Example 29: Synthesis of the compound shown in formula VIII'-10

[0186] The pre-dried reaction tube was cooled to room temperature under vacuum. In a glove box, 0.2 mmol (2.0 equiv.) of deuterium-containing alkylating reagent (the compound of formula II-7 prepared in Example 11), 0.1 mmol (1.0 equiv.) of enamide of formula Va, 0.2 mmol (2.0 equiv.) of tetramethylguanidine, 0.2 mL of anhydrous N,N-dimethylacetamide (DMA) and 0.8 mL of anhydrous toluene were added. The mixture was irradiated under a 450 nm blue lamp and stirred at 35 °C until the enamide disappeared as indicated by thin-layer chromatography (36 hours). The reaction solution was concentrated and separated by column chromatography using a silica gel column with ethyl acetate and petroleum ether as eluents to obtain the compound of formula VIII'-10.

[0187]

[0188] The experimental data for the compound shown in Formula VIII'-10 are as follows: Light yellow oil. Yield: 0.070 mmol, 19.1 mg, 70%. 1 H NMR(400MHz,Chloroform-d)δ7.33-7.27(m,1H),7.19-7.16(m,1H),7.11-7.07(m,1H), 6.87(d,J=7.8Hz,1H),3.23(s,3H),2.05-1.89(m,3H),1.85-1.74(m,1H),1.37(s,3H). 13 C NMR(151MHz,Chloroform-d)δ180.3,143.3,133.4,128.1,126.9(q,J=276.3Hz),122.8,122.5,108.3,48.2,37.2(t,J=14 .0Hz),33.7(q,J=28.8Hz),26.3,23.9.IR(ATR):2972,1702,1612,1469,1378,1257,1128,1054,752.HRMS(ESI):m / z[M+H] + calcd for C 14 H 15 D2NOF3 + :274.1382; found:274.1375. It has been verified that the obtained compound is the compound shown in formula VIII'-10.

[0189] Example 30: Synthesis of the compound shown in Formula IX-1

[0190] The pre-dried reaction tube was cooled to room temperature under vacuum. In a glove box, 0.1 mmol (1.0 equiv.) of deuterium-containing alkylating reagent (the compound of formula I-2 prepared in Example 2), 0.2 mmol (2.0 equiv.) of olefin of formula VI, 0.2 mmol (2.0 equiv.) of tetramethylguanidine, 0.3 mmol (3.0 equiv.) of deuterium water, and 1.0 mL of anhydrous dimethyl sulfoxide (DMSO) were added. The mixture was then irradiated under a 450 nm blue lamp and stirred at 35 °C until the amide disappeared as indicated by thin-layer chromatography (36 hours). The reaction solution was concentrated and separated by column chromatography using a silica gel column with ethyl acetate and petroleum ether as eluents to obtain the compound of formula IX-1.

[0191]

[0192] The experimental data for the compound shown in Formula IX-1 are as follows: Light yellow oil. Yield: 0.069 mmol, 22.0 mg, 69%, dr = 1:1. 1 H NMR(400MHz,Chloroform-d)(mixture of diastereomers)δ8.63(dd,J=8.0,4.0Hz,2H),8.47-8.41(m,2H),7.79(d,J=3.8Hz, 4H),7.56-7.49(m,2H),7.49-7.31(m,4H),2.38(d,J=14.0Hz,1H),2.24-2.08(m,2H ),1.90(d,J=14.0Hz,1H),1.60(s,6H),1.10-1.02(m,1H),1.00-0.93(m,2H),0.88- 0.80(m,1H),0.68(t,J=7.4Hz,2H),0.61(t,J=7.3Hz,3H),0.44(s,3H),0.37(s,3H). 13C NMR(151MHz,Chloroform-d)(mixture of diastereomers)δ164.4,164.1,160.4,147.74,147.68,139.19,139.15,136.7,1 36.3,134.4,128.5,127.5,126.97,126.95,126.7,126.6,126.5,123.2,123.0,1 21.5,117.4,49.2,49.0,46.8,46.5,31.4-31.1(m),30.7,30.0,28.4,28.2,20.4 ,19.6,11.1,10.7.IR(ATR):2968,1678,1600,1463,1354,1283,1117,1066,754cm -1 HRMS(ESI):m / z[M+Na] + calcd for C 21 H 21 DN2ONa + :342.1678; found:342.1687. Upon verification, the obtained compound is the compound shown in Formula IX-1.

[0193] Example 31: Synthesis of the compound shown in Formula IX-2

[0194] The pre-dried reaction tube was cooled to room temperature under vacuum. In a glove box, 0.1 mmol (1.0 equiv.) of deuterium-containing alkylating reagent (the compound of formula I-1 prepared in Example 1), 0.2 mmol (2.0 equiv.) of olefin of formula VI, 0.2 mmol (2.0 equiv.) of tetramethylguanidine, 0.3 mmol (3.0 equiv.) of deuterium water, and 1.0 mL of anhydrous dimethyl sulfoxide (DMSO) were added. The mixture was then irradiated under a 450 nm blue lamp and stirred at 35 °C until the amide disappeared as indicated by thin-layer chromatography (36 hours). The reaction solution was concentrated and separated by column chromatography using a silica gel column with ethyl acetate and petroleum ether as eluents to obtain the compound of formula IX-2.

[0195]

[0196] The experimental data for the compound shown in Formula IX-2 are as follows: Light yellow oil. Yield: 0.072 mmol, 22.0 mg, 72%. 1H NMR(400MHz,Chloroform-d)δ8.63(d,J=8.0Hz,1H),8.44(d,J=7.2Hz,1H),7.79(dd,J=4.7,2.2Hz,1H),7.56-7.49(m,1H),7 .48-7.41(m,1H),7.41-7.33(m,2H),2.28(d,J=13.9Hz,1H),2.02(d,J=14.0Hz,1H),1.60(s,3H),0.57(s,3H),0.46(s,3H). 13 CNMR(101MHz,Chloroform-d)δ164.3,160.4,147.7,139.2,136.5,134.4,128.5,127.5,127.0,126.8,126.6,123.0,12 1.5,117.4,49.1,48.7,28.5,25.4-25.1(m),24.1,23.1.IR(ATR):2971,1677,1599,1463,1354,1261,1192,1056,754cm -1 HRMS(ESI):m / z[M+Na] + calcd for C 20 H 19 DN2ONa + :328.1521; found:328.1531. It has been verified that the obtained compound is the compound shown in formula IX-2.

[0197] Example 32, Synthesis of the compound shown in Formula IX-3

[0198] The pre-dried reaction tube was cooled to room temperature under vacuum. In a glove box, 0.1 mmol (1.0 equiv.) of deuterium-containing alkylating reagent (the compound of formula I-3 prepared in Example 3), 0.2 mmol (2.0 equiv.) of olefin of formula VI, 0.2 mmol (2.0 equiv.) of tetramethylguanidine, 0.3 mmol (3.0 equiv.) of deuterium water, and 1.0 mL of anhydrous dimethyl sulfoxide (DMSO) were added. The mixture was then irradiated under a 450 nm blue lamp and stirred at 35 °C until the amide disappeared as indicated by thin-layer chromatography (36 hours). The reaction solution was concentrated and separated by column chromatography using a silica gel column with ethyl acetate and petroleum ether as eluents to obtain the compound of formula IX-3.

[0199]

[0200] The experimental data for the compound shown in Formula IX-3 are as follows: Light yellow oil. Yield: 0.073 mmol, 24.1 mg, 73%. 1 H NMR(400MHz,Chloroform-d)δ8.61(d,J=7.9Hz,1H),8.43(d,J=7.9Hz,1H),7.82-7.75(m,2H),7.54-7.48(m,1H),7.46-7.40(m,1H),7. 39-7.31(m,2H),2.37(d,J=13.8Hz,1H),2.15(d,J=13.7Hz,1H),1.60(s,3H),1.39-1.28(m,2H),1.21-1.06(m,4H),0.83-0.74(m,2H). 13 C NMR(151MHz,Chloroform-d)δ164.3,160.4,147.7,139.2,136.6,134.4,128.5,127.5,127.0,126.7,126.6,123.1,121.5 ,117.3,49.5,46.6,37.4-36.8(m),33.7,32.8,27.6,25.0,24.8.IR(ATR):2971,1681,1600,1464,1382,1250,1066,755cm - 1 HRMS(ESI):m / z[M+Na] + calcd for C 22 H 21 DN2ONa + 354.1677; found: 354.1687. Upon verification, the obtained compound is the compound shown in Formula IX-3.

[0201] Example 33, Synthesis of the compound shown in formula IX'-1

[0202] The pre-dried reaction tube was cooled to room temperature under vacuum. In a glove box, 0.1 mmol (1.0 equiv.) of deuterium-containing alkylating reagent (the compound of formula II-2 prepared in Example 6), 0.2 mmol (2.0 equiv.) of olefin of formula VI, 0.2 mmol (2.0 equiv.) of tetramethylguanidine, 0.3 mmol (3.0 equiv.) of deuterium water, and 1.0 mL of anhydrous dimethyl sulfoxide (DMSO) were added. The mixture was then irradiated under a 450 nm blue lamp and stirred at 35 °C until the amide disappeared as indicated by thin-layer chromatography (36 hours). The reaction solution was concentrated and separated by column chromatography using a silica gel column with ethyl acetate and petroleum ether as eluents to obtain the compound of formula IX'-1.

[0203]

[0204] The experimental data for the compound shown in Formula IX'-1 are as follows: Colorless oil. Yield: 0.069 mmol, 22.1 mg, 69%. 1 H NMR(400MHz,Chloroform-d)δ8.00(d,J=8.2Hz,2H),7.59-7.55(m,1H),7.49-7.40(m,2H ), 4.95 (d, J = 9.2Hz, 1H), 3.18-3.00 (m, 1H), 2.94-2.74 (m, 1H), 1.84 (s, 3H), 1.80 (s, 3H). 13 C NMR(151MHz,Chloroform-d)δ164.2,160.3,147.8,139.3,136.5,134.4,128.5,127.5,127.0,126.74,126.67,122. 7,121.5,117.3,49.4,40.6,31.7,26.3,22.3,14.0.IR(ATR):2922,1680,1600,1464,1317,1186,1117,1066,754cm -1 HRMS(ESI):m / z[M+Na] + calcd for C 21 H 20 D2N2ONa + 343.1740; found: 343.1750. It has been verified that the obtained compound is the compound shown in formula IX'-1.

[0205] Example 34, Synthesis of the compound shown in formula IX'-2

[0206] The pre-dried reaction tube was cooled to room temperature under vacuum. In a glove box, 0.1 mmol (1.0 equiv.) of deuterium-containing alkylating reagent (the compound of formula II-4 prepared in Example 8), 0.2 mmol (2.0 equiv.) of olefin of formula VI, 0.2 mmol (2.0 equiv.) of tetramethylguanidine, 0.3 mmol (3.0 equiv.) of deuterium water, and 1.0 mL of anhydrous dimethyl sulfoxide (DMSO) were added. The mixture was then irradiated under a 450 nm blue lamp and stirred at 35 °C until the amide disappeared as indicated by thin-layer chromatography (36 hours). The reaction solution was concentrated and separated by column chromatography using a silica gel column with ethyl acetate and petroleum ether as eluents to obtain the compound of formula IX'-2.

[0207]

[0208] The experimental data for the compound shown in Formula IX'-2 are as follows: Colorless oil. Yield: 0.058 mmol, 21.8 mg, 58%. 1 H NMR(400MHz,Chloroform-d)δ8.62(d,J=7.9Hz,1H),8.44(d,J=7.4Hz,1H),7.82-7.76(m,2H),7.58-7.49(m,1H),7.47-7.41(m, 1H),7.40-7.32(m,2H),2.19(d,J=13.3Hz,1H),1.96(d,J=13.3Hz,1H),1.62(s,3H),1.24-1.02(m,12H),0.82(t,J=7.0Hz,3H). 13 C NMR(151MHz,Chloroform-d)δ164.2,160.3,147.8,139.3,136.5,134.4,128.5,127.5,126.9,126.7,126.7,122.7,121.5,117.3, 49.4,40.6,31.9,29.51,29.47,29.3,29.2,26.3,22.7,14.2.IR(ATR):2921,1681,1600,1464,1354,1303,1186,1118,1021,754cm -1 HRMS(ESI):m / z[M+Na] + calcd for C 25 H 28 D2N2ONa + :399.2365; found:399.2376. It has been verified that the obtained compound is the compound shown in formula IX'-2.

[0209] Example 35: Synthesis of the compound shown in formula IX'-3

[0210] The pre-dried reaction tube was cooled to room temperature under vacuum. In a glove box, 0.1 mmol (1.0 equiv.) of deuterium-containing alkylating reagent (the compound of formula II-1 prepared in Example 5), 0.2 mmol (2.0 equiv.) of olefin of formula VI, 0.2 mmol (2.0 equiv.) of tetramethylguanidine, 0.3 mmol (3.0 equiv.) of deuterium water, and 1.0 mL of anhydrous dimethyl sulfoxide (DMSO) were added. The mixture was then irradiated under a 450 nm blue lamp and stirred at 35 °C until the amide disappeared as indicated by thin-layer chromatography (36 hours). The reaction solution was concentrated and separated by column chromatography using a silica gel column with ethyl acetate and petroleum ether as eluents to obtain the compound of formula IX'-3.

[0211]

[0212] The experimental data for the compound shown in Formula IX'-3 are as follows: Colorless oil. Yield: 0.050 mmol, 16.0 mg, 50%. 1 H NMR(400MHz,Chloroform-d)δ8.62(d,J=8.0Hz,1H),8.44(d,J=8.0Hz,1H),7.84-7.75(m,2H),7.56-7.49(m,1H),7.48-7.41(m,1H ),7.40-7.32(m,2H),2.20(d,J=13.2Hz,1H),1.98(d,J=13.2Hz,1H),1.63(s,3H),1.35(q,J=6.6Hz,1H),0.73(s,3H),0.71(s,3H). 13 C NMR(151MHz,Chloroform-d)δ164.1,160.4,147.8,139.3,136.5,134.4,128.5,127.6,127.0,126.74,126.70,122. 6,121.5,117.3,49.3,38.5,28.0,26.4,22.5,22.3.IR(ATR):2970,1680,1600,1463,1354,1253,1186,1056,754cm -1 HRMS(ESI):m / z[M+Na] + calcd for C 19 H 16 D2N2ONa +343.1739; found: 343.1750. It has been verified that the obtained compound is the compound shown in formula IX'-3.

[0213] Example 36, Synthesis of the compound shown in formula IX'-4

[0214] The pre-dried reaction tube was cooled to room temperature under vacuum. In a glove box, 0.1 mmol (1.0 equiv.) of deuterium-containing alkylating reagent (the compound of formula II-6 prepared in Example 10), 0.2 mmol (2.0 equiv.) of olefin of formula VI, 0.2 mmol (2.0 equiv.) of tetramethylguanidine, 0.3 mmol (3.0 equiv.) of deuterium water, and 1.0 mL of anhydrous dimethyl sulfoxide (DMSO) were added. The mixture was then irradiated under a 450 nm blue lamp and stirred at 35 °C until the amide disappeared as indicated by thin-layer chromatography (36 hours). The reaction solution was concentrated and separated by column chromatography using a silica gel column with ethyl acetate and petroleum ether as eluents to obtain the compound of formula IX'-4.

[0215]

[0216] The experimental data for the compound shown in Formula IX'-4 are as follows: Colorless oil. Yield: 0.052 mmol, 18.0 mg, 52%. 1 H NMR(400MHz,Chloroform-d)δ8.62(d,J=8.0Hz,1H),8.44(d,J=8.7Hz,1H),7.84-7.75(m,2H),7.56-7.49(m,1H),7.47-7.42(m, 1H),7.40-7.34(m,2H),2.22(d,J=13.3Hz,1H),1.98(d,J=13.3Hz,1H),1.67-1.49(m,6H),1.46-1.34(m,4H),0.89-0.79(m,2H). 13 C NMR(151MHz,Chloroform-d)δ164.2,160.4,147.8,139.3,136.5,134.4,128.4,127.6,126.9,126.73,126.70,122.6,121 .5,117.3,49.4,40.0,39.8,32.6,32.4,26.3,25.2.IR(ATR):2944,1680,1601,1464,1355,1283,1303,1186,1066,754cm -1 HRMS(ESI):m / z[M+Na] +calcd for C 23 H 22 D2N2ONa + 369.1895; found: 369.1906. It has been verified that the obtained compound is the compound shown in formula IX'-4.

[0217] Example 37: Synthesis of the compound shown in formula IX'-5

[0218] The pre-dried reaction tube was cooled to room temperature under vacuum. In a glove box, 0.1 mmol (1.0 equiv.) of deuterium-containing alkylating reagent (the compound of formula II-5 prepared in Example 9), 0.2 mmol (2.0 equiv.) of olefin of formula VI, 0.2 mmol (2.0 equiv.) of tetramethylguanidine, 0.3 mmol (3.0 equiv.) of deuterium water, and 1.0 mL of anhydrous dimethyl sulfoxide (DMSO) were added. The mixture was then irradiated under a 450 nm blue lamp and stirred at 35 °C until the amide disappeared as indicated by thin-layer chromatography (36 hours). The reaction solution was concentrated and separated by column chromatography using a silica gel column with ethyl acetate and petroleum ether as eluents to obtain the compound of formula IX'-5.

[0219]

[0220] The experimental data for the compound shown in Formula IX'-5 are as follows: Colorless oil (124 mg, 0.166 mmol, 83%). Yield: 0.050 mmol, 18.0 mg, 50%. 1 H NMR(400MHz,Chloroform-d)δ8.60(d,J=7.9Hz,1H),8.45-8.39(d,J=7.9Hz,1H),7.82-7.72(m,2H),7.53-7.48(m,1H),7.45-7.40(m,1H) ,7.39-7.30(m,2H),2.19(d,J=13.2Hz,1H),1.97(d,J=13.2Hz,1H),1.60(s,3H),1.59-1.47(m,5H),1.13-0.95(m,4H),0.72-0.57(m,2H). 13C NMR(151MHz,Chloroform-d)δ164.2,160.4,147.8,139.3,136.5,134.4,128.4,127.5,126.9,126.72,126.68,122. 6,121.5,117.3,49.4,38.0,37.6,33.2,33.0,26.6,26.3.IR(ATR):2972,1682,1601,1464,1356,1230,1056,755cm -1 HRMS(ESI):m / z[M+Na] + calcd for C 24 H 24 D2N2ONa + :383.2052; found:383.2063. Upon verification, the obtained compound is the compound shown in formula IX'-5.

[0221] Example 38, Synthesis of the compound shown in formula IX'-6

[0222] The pre-dried reaction tube was cooled to room temperature under vacuum. In a glove box, 0.1 mmol (1.0 equiv.) of deuterium-containing alkylating reagent (the compound of formula II-10 prepared in Example 14), 0.2 mmol (2.0 equiv.) of olefin of formula VI, 0.2 mmol (2.0 equiv.) of tetramethylguanidine, 0.3 mmol (3.0 equiv.) of deuterium water, and 1.0 mL of anhydrous dimethyl sulfoxide (DMSO) were added. The mixture was then irradiated under a 450 nm blue lamp and stirred at 35 °C until the amide disappeared as indicated by thin-layer chromatography (36 hours). The reaction solution was concentrated and separated by column chromatography using a silica gel column with ethyl acetate and petroleum ether as eluents to obtain the compound of formula IX'-6.

[0223]

[0224] The experimental data for the compound shown in Formula IX'-6 are as follows: White solid. Yield: 0.055 mmol, 21.0 mg, 55%. 1H NMR(400MHz,Chloroform-d)δ8.62(d,J=8.0Hz,1H),8.44(d,J=7.8Hz,1H),7.8 5-7.77(m,2H),7.57-7.48(m,1H),7.47-7.41(m,1H),7.40-7.33(m,2H),7.18- 7.11(m,2H),7.11-7.05(m,1H),7.00(d,J=7.8Hz,2H),2.40(t,J=7.9Hz,2H),2 .26(d,J=13.3Hz,1H),2.00(d,J=13.3Hz,1H),1.63(s,3H),1.47-1.41(m,2H). 13 C NMR(101MHz,Chloroform-d)δ164.1,160.3,147.8,142.4,139.3,136.4,134.4,128.5,128.4,128.3,127.6,127.0,126.8, 126.7,125.7,122.7,121.5,117.3,49.4,40.3,35.4,31.3,26.2.IR(ATR):2972,1678,1601,1464,1382,1229,1066,755cm -1 HRMS(ESI):m / z[M+Na] + calcd forC 26 H 22 D2N2ONa + :405.1895; found:405.1906. It has been verified that the obtained compound is the compound shown in formula IX'-6.

[0225] Example 39: Synthesis of the compound shown in formula IX'-7

[0226] The pre-dried reaction tube was cooled to room temperature under vacuum. In a glove box, 0.1 mmol (1.0 equiv.) of deuterium-containing alkylating reagent (the compound of formula II-8 prepared in Example 12), 0.2 mmol (2.0 equiv.) of olefin of formula VI, 0.2 mmol (2.0 equiv.) of tetramethylguanidine, 0.3 mmol (3.0 equiv.) of deuterium water, and 1.0 mL of anhydrous dimethyl sulfoxide (DMSO) were added. The mixture was then irradiated under a 450 nm blue lamp and stirred at 35 °C until the amide disappeared as indicated by thin-layer chromatography (36 hours). The reaction solution was concentrated and separated by column chromatography using a silica gel column with ethyl acetate and petroleum ether as eluents to obtain the compound of formula IX'-7.

[0227]

[0228] The experimental data for the compound shown in Formula IX'-7 are as follows: Colorless oil. Yield: 0.059 mmol, 22.1 mg, 59%. 1 H NMR(400MHz,Chloroform-d)δ8.61(d,J=8.0Hz,1H),8.42(d,J=7.9Hz,1H),7.78(d,J=3.4Hz,2H),7.52(m,1H),7.47-7.42(m ,1H),7.41-7.33(m,2H),2.23(d,J=13.2Hz,1H),1.97(d,J=13.3Hz,1H),1.94-1.76(m,2H),1.62(s,3H),1.45-1.36(m,2H). 13 C NMR(151MHz,Chloroform-d)δ163.7,160.2,147.7,139.3,136.0,134.5,128.7,127.5,127.0,127.03(d,J=276.3Hz),126.9,12 6.8,122.6,121.5,117.4,49.2,40.0,33.4(q,J=28.5Hz),26.3,21.7.IR(ATR):2972,1680,1600,1453,1355,1242,1056,755cm -1 .HRMS(ESI):m / z[M+H] + calcd for C 21 H 18 D2N2F3O + 375.1648; found: 375.1638. Upon verification, the obtained compound is the compound shown in formula IX'-7.

[0229] Example 40: Synthesis of the compound shown in Formula X-1

[0230] The pre-dried reaction tube was cooled to room temperature under vacuum. In a glove box, 0.1 mmol (1.0 equiv.) of deuterium-containing alkylating reagent (the compound of formula I-1 prepared in Example 1), 0.2 mmol (2.0 equiv.) of isonitrile of formula VII, 0.2 mmol (2.0 equiv.) of diisopropylethylamine, and 1.0 mL of anhydrous dimethyl sulfoxide (DMSO) were added. The mixture was then irradiated under a 450 nm blue lamp and stirred at 35 °C until the amide disappeared as indicated by thin-layer chromatography (36 hours). The reaction solution was concentrated and separated by column chromatography using a silica gel column with ethyl acetate and petroleum ether as eluents to obtain the compound of formula X-1.

[0231]

[0232] The experimental data for the compound shown in Formula X-1 are as follows: Colorless oil. Yield: 0.072 mmol, 16.0 mg, 72%. 1 H NMR(400MHz,Chloroform-d)δ8.64(d,J=8.5Hz,1H),8.53(d,J=8.1Hz,1H),8.31(d,J=8.3Hz,1H ),8.14(d,J=8.2Hz,1H),7.85-7.76(m,1H),7.74-7.63(m,2H),7.63-7.56(m,1H),1.51(s,6H). 13 C NMR(151MHz,Chloroform-d)δ166.0,144.0,133.2,130.1,128.5,127.3,126.3,125.8,124.9,123.6 ,122.7,122.0,31.4-31.0(m),22.0.IR(ATR):2962,1610,1571,1456,1349,1236,1152,1010,755cm -1 HRMS(ESI):m / z[M+Na] + calcd forC 16 H 14 DNNa + :245.1160; found:245.1152. It has been verified that the obtained compound is the compound shown in formula X-1.

[0233] Example 41: Synthesis of the compound shown in formula X-2

[0234] The pre-dried reaction tube was cooled to room temperature under vacuum. In a glove box, 0.1 mmol (1.0 equiv.) of deuterium-containing alkylating reagent (the compound of formula I-2 prepared in Example 2), 0.2 mmol (2.0 equiv.) of isonitrile of formula VII, 0.2 mmol (2.0 equiv.) of diisopropylethylamine, and 1.0 mL of anhydrous dimethyl sulfoxide (DMSO) were added. The mixture was then irradiated under a 450 nm blue lamp and stirred at 35 °C until the amide disappeared as indicated by thin-layer chromatography (36 hours). The reaction solution was concentrated and separated by column chromatography using a silica gel column with ethyl acetate and petroleum ether as eluents to obtain the compound of formula X-2.

[0235]

[0236] The experimental data for the compound shown in formula X-2 are as follows: Colorless oil. Yield: 0.077 mmol, 18.2 mg, 77%. 1 H NMR(400MHz,Chloroform-d)δ8.65(d,J=8.2Hz,1H),8.54(d,J=8.1Hz,1H),8.31(d,J=8.3Hz,1H),8.13(d,J=8.1Hz,1H),7.85 -7.76(m,1H),7.74-7.64(m,2H),7.63-7.56(m,1H),2.21-2.09(m,1H),1.87-1.74(m,1H),1.47(s,3H),0.97(t,J=7.4Hz,3H). 13 C NMR(151MHz,Chloroform-d)δ165.6,144.0,133.1,130.08,130.06,128.5,127.2,126.3,125.8,125.4,123 .4,122.7,122.0,38.4-37.9(m),29.2,19.8,12.6.IR(ATR):2959,1609,1570,1454,1351,1149,1004,755cm -1 .HRMS(ESI):m / z[M+H] + calcd for C 17 H 17 DN + :237.1497; found:237.1487. It has been verified that the obtained compound is the compound shown in formula X-2.

[0237] Example 42, Synthesis of the compound shown in formula X'-1

[0238] The pre-dried reaction tube was cooled to room temperature under vacuum. In a glove box, 0.1 mmol (1.0 equiv.) of deuterium-containing alkylating reagent (the compound shown in Formula II-2 prepared in Example 6), 0.2 mmol (2.0 equiv.) of isonitrile shown in Formula VII, 0.2 mmol (2.0 equiv.) of diisopropylethylamine, and 1.0 mL of anhydrous dimethyl sulfoxide (DMSO) were added. The mixture was then irradiated under a 450 nm blue lamp and stirred at 35 °C until the amide disappeared as indicated by thin-layer chromatography (36 hours). The reaction solution was concentrated and separated by column chromatography using a silica gel column with ethyl acetate and petroleum ether as eluents to obtain the compound shown in Formula X'-1.

[0239]

[0240] The experimental data for the compound represented by formula X'-1 are as follows: Colorless oil. Yield: 0.067 mmol, 15.9 mg, 67%. 1 H NMR(400MHz,Chloroform-d)δ8.65(d,J=8.8Hz,1H),8.55(d,J=8.2Hz,1H),8.26(d,J=8.3Hz,1H),8.12(d,J=8.2Hz,1H), 7.86-7.79(m,1H),7.74-7.66(m,2H),7.68-7.57(m,1H),1.89(t,J=7.6Hz,2H),1.61-1.49(m,2H),1.01(t,J=7.4Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ162.7,143.9,133.1,130.4,129.7,128.7,127.3,1 26.5,126.4,125.4,123.8,122.6,122.0,31.8,23.2,14.2.HRMS(ESI):m / z[M+Na] + calcd for C 17 H 15 D2NNa + :260.1379; found:260.1371. It has been verified that the obtained compound is the compound shown in formula X'-1.

[0241] Example 43, Synthesis of the compound shown in formula X'-2

[0242] The pre-dried reaction tube was cooled to room temperature under vacuum. In a glove box, 0.1 mmol (1.0 equiv.) of deuterium-containing alkylating reagent (the compound shown in Formula II-6 prepared in Example 10), 0.2 mmol (2.0 equiv.) of isonitrile shown in Formula VII, 0.2 mmol (2.0 equiv.) of diisopropylethylamine, and 1.0 mL of anhydrous dimethyl sulfoxide (DMSO) were added. The mixture was then irradiated under a 450 nm blue lamp and stirred at 35 °C until the amide disappeared as indicated by thin-layer chromatography (36 hours). The reaction solution was concentrated and separated by column chromatography using a silica gel column with ethyl acetate and petroleum ether as eluents to obtain the compound shown in Formula X'-2.

[0243]

[0244] The experimental data for the compound shown in formula X'-2 are as follows: Colorless oil. Yield: 0.092 mmol, 24.2 mg, 92%. 1H NMR(400MHz,Chloroform-d)δ8.63(d,J=8.3Hz,1H),8.53(d,J=8.2Hz,1H),8.28(d,J=8.2Hz,1H),8.13(d,J=8.2Hz,1H) ,7.87-7.77(m,1H),7.74-7.64(m,2H),7.63-7.56(m,1H),2.50(t,J=7.8Hz,1H),1.80-1.63(m,4H),1.59-1.36(m,4H). 13 C NMR(151MHz,Chloroform-d)δ162.1,143.9,133.1,130.4,129.8,128.7,127.3,126.7,126.4,1 25.6,123.8,122.6,122.0,40.4,32.8,25.2.IR(ATR):2942,1610,1483,1353,1223,1066,757cm -1 .HRMS(ESI):m / z[M+H] + calcd for C 19 H 18 D2N + :264.1716; found:264.1707. It has been verified that the obtained compound is the compound shown in formula X'-2.

[0245] Example 44, Synthesis of the compound shown in formula X'-3

[0246] The pre-dried reaction tube was cooled to room temperature under vacuum. In a glove box, 0.1 mmol (1.0 equiv.) of deuterium-containing alkylating reagent (the compound of formula II-11 prepared in Example 15), 0.2 mmol (2.0 equiv.) of isonitrile of formula VII, 0.2 mmol (2.0 equiv.), diisopropylethylamine (0.2 mmol (2.0 equiv.)) and 1.0 mL of anhydrous dimethyl sulfoxide (DMSO) were added. The mixture was then irradiated under a 450 nm blue lamp and stirred at 35 °C until the amide disappeared as indicated by thin-layer chromatography (36 hours). The reaction solution was concentrated and separated by column chromatography using a silica gel column with ethyl acetate and petroleum ether as eluents to obtain the compound of formula VII-5.

[0247]

[0248] The experimental data for the compound shown in formula X'-3 are as follows: Colorless oil. Yield: 0.071 mmol, 16.7 mg, 71%. 1H NMR(400MHz,Chloroform-d)δ8.65(d,J=8.4Hz,1H),8.54(d,J=8.2Hz,1H),8.25(d,J=8.3Hz,1H),8.12(d,J=8.2Hz,1H),7.88-7.79(m,1H),7 .77-7.66(m,2H),7.66-7.58(m,1H),6.12-5.98(m,1H),5.17(d,J=17.1Hz,1H),5.04(d,J=10.2Hz,1H).,3.45(s,1H),2.70(d,J=7.7Hz,1H). 13 C NMR(151MHz,Chloroform-d)δ161.4,143.9,138.2,133.1,130.5,129.8,128.8,127.4,126.5,126.3,125.4,1 23.8,122.7,122.1,115.2,35.4,33.2(t,J=7.4Hz).IR(ATR):2926,1687,1612,1418,1365,1246,1155,753cm -1 .HRMS(ESI):m / z[M+H] + calcd for C 17 H 14 D2N + :236.1403; found:236.1396. It has been verified that the obtained compound is the compound shown in formula X'-3.

[0249] Example 45, Synthesis of the compound shown in formula X'-4

[0250] The pre-dried reaction tube was cooled to room temperature under vacuum. In a glove box, 0.1 mmol (1.0 equiv.) of deuterium-containing alkylating reagent (the compound shown in Formula II-9 prepared in Example 13), 0.2 mmol (2.0 equiv.) of isonitrile shown in Formula VII, 0.2 mmol (2.0 equiv.) of diisopropylethylamine, and 1.0 mL of anhydrous dimethyl sulfoxide (DMSO) were added. The mixture was then irradiated under a 450 nm blue lamp and stirred at 35 °C until the amide disappeared as indicated by thin-layer chromatography (36 hours). The reaction solution was concentrated and separated by column chromatography using a silica gel column with ethyl acetate and petroleum ether as eluents to obtain the compound shown in Formula X'-4.

[0251]

[0252] The experimental data for the compound shown in formula X'-4 are as follows: White solid. Yield: 0.084 mmol, 23.9 mg, 84%. 1 H NMR (400MHz, CDCl3) δ8.64(d,J=8.2Hz,1H),8.55(d,J=6.9Hz,1H),8.25(d,J=8.2Hz,1H),8.15(d, J=8.2Hz,1H),7.87-7.78(m,1H),7.77-7.57(m,3H),7.35(m,4H),7.27-7.21(m,1H),3.27(s,2H). 13 C NMR(151MHz,Chloroform-d)δ161.1,143.9,142.1,133.1,130.5,129.8,128.8,128.6,127.5,126.6,12 6.2,126.1,125.3,123.8,122.7,122.1,35.0.IR(ATR):2988,2157,1958,1535,1464,1394,1066,757cm -1 HRMS(ESI):m / z[M+Na] + calcd for C 21 H 15 D2NNa + :308.1379; found:308.1366. Upon verification, the obtained compound is the compound shown in formula X'-4.

[0253] Example 46, Synthesis of the compound shown in formula X'-5

[0254] The pre-dried reaction tube was cooled to room temperature under vacuum. In a glove box, 0.1 mmol (1.0 equiv.) of deuterium-containing alkylating reagent (the compound shown in Formula II-10 prepared in Example 14), 0.2 mmol (2.0 equiv.) of isonitrile shown in Formula VII, 0.2 mmol (2.0 equiv.) of diisopropylethylamine, and 1.0 mL of anhydrous dimethyl sulfoxide (DMSO) were added. The mixture was then irradiated under a 450 nm blue lamp and stirred at 35 °C until the amide disappeared as indicated by thin-layer chromatography (36 hours). The reaction solution was concentrated and separated by column chromatography using a silica gel column with ethyl acetate and petroleum ether as eluents to obtain the compound shown in Formula X'-5.

[0255]

[0256] The experimental data for the compound shown in formula X'-5 are as follows: White solid. Yield: 0.071 mmol, 21.2 mg, 71%.1 H NMR(400MHz,Chloroform-d)δ8.63(d,J=8.3Hz,1H),8.54(d,J=8.2Hz,1H),8.16-8.08(m,2H),7.85-7.76(m,1H),7.75- 7.68(m,1H),7.67-7.59(m,2H),7.33-7.26(m,4H),7.21(d,J=7.0Hz,1H),2.86(t,J=7.7Hz,2H),2.26(t,J=7.7Hz,2H). 13 C NMR(151MHz,Chloroform-d)δ162.0,143.9,142.3,133.1,130.4,129.7,128.74,128.72,128.5,127.4,126.5,126 .3,126.0,125.3,123.8,122.6,122.1,36.1,30.9.IR(ATR):2930,1608,1582,1453,1319,1233,1136,1081,720cm -1 HRMS(ESI):m / z[M+Na] + calcd forC 22 H 17 D2NNa + :322.1535; found:322.1525. It has been verified that the obtained compound is the compound shown in formula X'-5.

[0257] Example 47: Synthesis of the compound shown in formula X'-6

[0258] The pre-dried reaction tube was cooled to room temperature under vacuum. In a glove box, 0.1 mmol (1.0 equiv.) of deuterium-containing alkylating reagent (the compound shown in Formula II-8 prepared in Example 12), 0.2 mmol (2.0 equiv.) of isonitrile shown in Formula VII, 0.2 mmol (2.0 equiv.) of diisopropylethylamine, and 1.0 mL of anhydrous dimethyl sulfoxide (DMSO) were added. The mixture was then irradiated under a 450 nm blue lamp and stirred at 35 °C until the amide disappeared as indicated by thin-layer chromatography (36 hours). The reaction solution was concentrated and separated by column chromatography using a silica gel column with ethyl acetate and petroleum ether as eluents to obtain the compound shown in Formula X'-6.

[0259]

[0260] The experimental data for the compound shown in formula X'-6 are as follows: White solid. Yield: 0.090 mmol, 18.1 mg, 90%.1 H NMR(400MHz,Chloroform-d)δ8.67(d,J=8.2Hz,1H),8.57(d,J=8.2Hz,1H),8.22(d,J=7.9Hz,1H), 8.13(d,J=8.2Hz,1H),7.91-7.81(m,1H),7.77-7.69(m,2H),7.69-7.62(m,1H),2.44-2.22(m,4H). 13 C NMR (151MHz, Chloroform-d) δ 160.1, 143.7, 133.1, 130.7, 129.8, 128.9, 127.62 (q, J = 272.6Hz), 127.6, 126.8, 125. 8,125.3,123.8,122.8,122.1,33.6(q,28.7Hz),20.8.IR(ATR):2941,1584,1528,1444,1309,1251,1133,998,752cm - 1 .HRMS(ESI):m / z[M+H] + calcd for C 17 H 13 D2NF3 + :292.1277; found:292.1267. Upon verification, the obtained compound is the compound shown in formula X'-6.

[0261] The present invention has been described in detail above. Those skilled in the art will recognize that the invention can be practiced in a wide range of ways with equivalent parameters, concentrations, and conditions without departing from its spirit and scope. While specific embodiments have been provided, it should be understood that further modifications can be made to the invention. In summary, according to the principles of the invention, this application is intended to include any changes, uses, or improvements to the invention, including modifications made using conventional techniques known in the art that depart from the scope disclosed herein.

Claims

1. A method for synthesizing the compound shown in Formula I or Formula II, comprising the following steps: In Equations I-II, R 1 R 2 Each is independently selected from hydrogen, C1-C7 alkyl, phenyl or benzyl or alkenyl or trifluoromethyl-substituted alkyl; or, R 1 R 2 It forms C3-C8 cycloalkyl groups with carbons in the main chain; R 3 Selected from C1-C7 alkyl groups, C3-C8 cycloalkyl groups, phenyl groups, phenyl-substituted alkyl groups, benzyl or alkenyl-substituted alkyl groups, or trifluoromethyl-substituted alkyl groups; Under alkaline conditions, the compound shown in Formula III or Formula IV undergoes a hydrogen-deuterium exchange reaction when heated in deuterium water to obtain the compound shown in Formula I or Formula II. In Equations III-IV, R 1 R 2 R 3 The definitions are the same as those in Equation I and Equation II; The temperature for the hydrogen-deuterium exchange reaction is 60~110℃; The hydrogen-deuterium exchange reaction is carried out under vacuum conditions.

2. The synthesis method according to claim 1, characterized in that: The ratio of the compound shown in Formula III or Formula IV to deuterium water is 1 mmol: 1.0 mL; The alkali is triethylamine or potassium carbonate, and the molar ratio of the compound shown in Formula III or Formula IV to triethylamine is 1:(0.2~1), and the molar ratio of the compound shown in Formula III or Formula IV to potassium carbonate is 1:(0.5~2). The hydrogen-deuterium exchange reaction takes 3 to 12 hours.

3. A method for synthesizing the compound shown in formula VIII or VIII', comprising the following steps: Under the presence of a base, the compound of formula I or formula II shown in claim 1 is reacted with the compound of formula V in an organic solvent under visible light to obtain the compound of formula VIII or formula VIII'. In equation VIII, R 1 R 2 The definition is the same as formula I; In equation VIII', R 3 The definition is the same as in formula II; In equations V, VIII, and VIII', R 4 It can be methyl, ethyl, phenyl, or benzyl.

4. The synthesis method according to claim 3, characterized in that: The molar ratio of the compound shown in Formula I or Formula II to the compound shown in Formula V is (1.5~3):1; The molar ratio of the compound shown in Formula I or Formula II to the alkali is (0.5~3):1; The base is selected from at least one of tetramethylguanidine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,4-diazabicyclo[2.2.2]octane, triethylamine, diethylamine, N,N-diisopropylethylamine, potassium carbonate, cesium carbonate, potassium phosphate, and sodium bicarbonate; The organic solvent is selected from at least one of toluene, xylene, chlorobenzene, benzene, dioxane, tetrahydrofuran, diethyl ether, chloroform, dichloromethane, 1,2-dichloroethane, ethyl acetate, acetone, acetonitrile, N,N-dimethylformamide, and N,N-dimethylformamide. The visible light is blue light with a wavelength of 450nm; The reaction temperature is 30~40℃. o C, the time is 24~48 hours.

5. A method for synthesizing the compound shown in formula X or formula X', comprising the following steps: In the presence of a base, the compound of formula I or formula II shown in claim 1 is reacted with the compound of formula VII in an organic solvent to obtain the compound of formula X or formula X'. In formula X, R 1 R 2 The definition is the same as formula I; In formula X', R 3 The definition is the same as in Formula II.

6. The synthesis method according to claim 5, characterized in that: The molar ratio of the compound shown in Formula I or Formula II to the compound shown in Formula VII is 1:(1~3); The molar ratio of the compound shown in Formula I or Formula II to the alkali is 1:(1~3); The base is selected from at least one of tetramethylguanidine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,4-diazabicyclo[2.2.2]octane, triethylamine, diethylamine, N,N-diisopropylethylamine, potassium carbonate, cesium carbonate, potassium phosphate, and sodium bicarbonate; The organic solvent is selected from at least one of toluene, xylene, chlorobenzene, benzene, dioxane, tetrahydrofuran, diethyl ether, chloroform, dichloromethane, 1,2-dichloroethane, dimethyl sulfoxide, ethyl acetate, acetone, acetonitrile, N,N-dimethylformamide, and N,N-dimethylformamide. The visible light is blue light with a wavelength of 450nm; The reaction temperature is 30~40℃. o C, the time is 24~48 hours.

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