Deuterium-containing alkyl reagent as well as synthesis method and application thereof

Abstract

The invention discloses a deuterium-containing alkyl reagent as well as a synthesis method and application thereof. The structural formula of the deuterium-containing alkyl reagent is shown as a formula I or a formula II. Alkyl triphenyl phosphine iodide is used as a raw material, hydrogen-deuterium exchange is carried out in deuterium water through heating, and the deuterium band alkylation reagent is prepared. The method is simple and convenient in process, high in yield and capable of realizing 10-gram-level large-scale preparation, more importantly, the deuterium band alkylation reagent can be used as a free radical reagent to be applied to free radical addition reaction to prepare different types of deuterium band alkylation products, and the deuterium band alkylation reagent has important application value. # imgabs0 #

Description

Technical Field

[0001] The invention belongs to the field of synthesis and application of important organic chemical reagents, and specifically relates to a deuterated alkyl reagent and a synthesis method and application thereof. Background Art

[0002] Deuterium substitution has long been sought in medical science, as replacing hydrogen with deuterium can alter pharmacokinetic properties and metabolic stability, thereby potentially enhancing therapeutic efficacy and reducing toxicity. In addition, deuterated compounds are widely used in reaction mechanism studies, structure determination, drug metabolism analysis, and performance improvement of organic light-emitting diodes. Therefore, the development of effective deuterated alkyl reagents to selectively install different deuterated alkyl groups into compounds will greatly accelerate the discovery and development of deuterium-functionalized molecules in various fields.

[0003] Although various deuteration conversion methods have been developed, achieving high deuterium content and excellent regioselectivity in the alkyl chain remains challenging. Transition metal-catalyzed direct hydrogen isotope exchange (HIE) reactions have been widely used in the deuteration of aromatic C(sp 2 )-H bonds are well established in the deuterium labeling (Angew. Chem. Int. Ed. 2018, 57, 3022-3047). However, direct HIE on aliphatic substrates remains underdeveloped and is generally limited to α-oxy, α-thiol, α-amino, benzyl, and acidic C(sp 3 )-H bonds. Photoredox catalysis has been used to 3 )-H bonds. For example, MacMillan and co-workers demonstrated methods for α-deuteration and tritritation of complex drugs using photocatalysts and hydrogen atom transfer catalysts (Science 2017, 358, 1182-1187.). Despite these advances, these deuteration protocols are generally applicable to hydrogenated or acidic C(sp 3 )-H bonds, but often encounter difficulties in terms of deuterium content and regioselectivity. Radical defunctionalization-deuteration reactions can regioselectively install a deuterium atom (d1), but this approach is limited by the lack of methods to selectively install a leaving group on the alkyl moiety.

[0004] To promote the development of diversified deuterated drugs, considerable efforts have been made to discover stable, cost-effective and readily available deuterated reagents. However, most studies have focused on d3-methylating agents such as CD3I, (CD3)2SO, (CD3)2SO4, CD3OD, 5-(d3-methyl)dibenzothiophene salts, cyclic sulfoxide amines, 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 ((d n -alkyl)-diphenylsulfonate) is used to introduce a deuterium atom at the α position of the heteroatom (Angew. Chem. Int. Ed. 2023, 62, e202311058). However, due to steric hindrance, the S-based N 2-process approaches may have difficulty installing sterically hindered d1-alkylating groups. In addition, the introduction of deuterium into alkyl chains remains challenging due to the lack of readily available carbon nucleophiles. Compared with ionic reactions, free radical reactions have several advantages: they are relatively insensitive to steric hindrance, are highly compatible with a variety of functional groups, and enable the formation of a variety of carbon-carbon bonds through free radical addition to multiple unsaturated bonds. Therefore, an ideal solution to address the limitations of ionic processes is to use free radical deuterated alkyl reagents, but such reagents have been rarely explored. Recently, the research groups of Lu, Shi, etc. developed d1-deuterated alkyl reagents. 2,3 -alkylsulfonates can be used as d 2,3 -alkyl radical precursors for CC bond formation (Angew. Chem. Int. Ed. 2024, e202409862; Nat. Commun. 2024, 15, 5067.). Despite these advances, a significant challenge remains: the difficulty of achieving the introduction of d1 within the alkyl chain, because current strategies do not allow the synthesis of d1-alkylating agents under their conditions. Given the important uses of deuterated alkyl reagents, the development of novel and efficient deuterated alkyl reagents and their application in the synthesis of biologically active compounds is currently a very challenging and meaningful research field. Summary of the invention

[0005] In order to further promote the development of deuterated alkylation reagents and provide more usable reagents and methods for organic synthesis and new drug research and development, the purpose of the present invention is to provide a deuterated alkylation reagent and a synthesis method and application thereof. The synthesis method of the deuterated alkylation reagent is simple and can be applied to the preparation of different types of trifluoromethylation products in free radical deuterated alkylation reactions.

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

[0007]

[0008] In Formula I to Formula II, R 1 , R 2 Each is independently selected from hydrogen, C1-C7 alkyl, phenyl, benzyl, alkenyl, trifluoromethyl substituted alkyl; or, R 1 , R 2 Form a C3-C8 cycloalkyl group with the carbon on the main chain;

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

[0010] In the compound, the C1-C7 alkyl group includes, but is 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 group includes, but is 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 a methyl group and an ethyl group;

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

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

[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 of the following:

[0017]

[0018] In a second aspect, the present invention provides a method for synthesizing a compound of formula I or formula II (i.e., deuterated alkyl triphenylphosphine iodide), comprising the following steps: in the presence of a base, heating the compound of formula III or formula IV in deuterated water to perform a hydrogen-deuterium exchange reaction to obtain a compound of formula I or formula II;

[0019]

[0020] In formula III to formula IV, R 1 , R 2 , R 3 The definitions of are the same as those of Formula I to Formula II.

[0021] In the above-mentioned synthesis method, the feed ratio of the compound represented by Formula III or Formula IV to deuterated water is 1 mmol: 1.0 mL;

[0022] The base is triethylamine or potassium carbonate, and the molar ratio of the compound represented by formula III or formula IV to triethylamine is 1:(0.2-1), specifically 1:0.2; the molar ratio of the compound represented by formula III or formula IV to potassium carbonate is 1:(0.5-2), specifically 1:1;

[0023] The temperature of the hydrogen-deuterium exchange reaction is 60-110° C., and the time is 3-12 hours, such as reacting at 100° C. for 6 hours;

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

[0025] In the above-mentioned synthesis method, the method further comprises the following post-treatment 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 then concentrating, adding ether and filtering and separating.

[0026] In a third aspect, the invention provides an application of a compound represented by protected formula I or formula II as a free radical deuterated alkylation reagent in the preparation of a deuterated alkylation product.

[0027] In a fourth aspect, a method for synthesizing a compound represented by protected formula VIII or formula VIII' (ie, an oxidized indole compound having a deuterated alkyl group) of the present invention comprises the following steps:

[0028] In the presence of a base, the compound represented by formula I or formula II reacts with the compound represented by formula V in an organic solvent under visible light to obtain a compound represented by formula VIII or formula VIII';

[0029]

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

[0031] In Formula VIII', R 3 The definition of is the same as that of formula II;

[0032] In Formula V, Formula VIII and Formula VIII', R 4 It is methyl, ethyl, phenyl or benzyl.

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

[0034]

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

[0036] The molar ratio of the compound represented by formula I or formula II to the base 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), 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 450nm wavelength blue light;

[0040] The reaction temperature is 30-40° C., and the reaction time is 24-48 hours, such as reacting at 35° C. for 36 hours.

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

[0042] In a fifth aspect, a method for synthesizing a compound represented by the protected formula IX or IX' (ie, a quinazolinone compound having a deuterated alkyl group) of the present invention comprises the following steps:

[0043] In the presence of a base, the compound represented by formula I or formula II reacts with the compound represented by formula VI in deuterated water and an organic solvent under visible light to obtain a compound represented by formula IX or formula IX';

[0044]

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

[0046] In Formula IX, R 3 The definition of is the same as that of formula II.

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

[0048] The molar ratio of the compound represented by 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 deuterated water to the compound represented by Formula I or Formula II is (1-6):1, such as 3:1; or the molar ratio of the deuterated water to the compound represented by 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), 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 450nm wavelength blue light;

[0053] The reaction temperature is 30-40° C., and the reaction time is 24-48 hours, such as reacting at 35° C. for 36 hours.

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

[0055] In a sixth aspect, a method for synthesizing a compound represented by a protective formula X or formula X' (i.e., a phenanthridine compound having a deuterated alkyl group) of the present invention comprises the following steps:

[0056] In the presence of a base, the compound represented by formula I or formula II reacts with the compound represented by formula VII in an organic solvent to obtain a compound represented by formula X or formula X';

[0057]

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

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

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

[0061] The molar ratio of the compound represented by formula I or formula II to the base can be 1:(1-3), 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), 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 450nm wavelength blue light;

[0065] The reaction temperature is 30-40° C., and the reaction time is 24-48 hours, such as reacting at 35° C. for 36 hours.

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

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

[0068] The invention uses alkyl triphenylphosphine iodide as a raw material, and in the presence of a base, performs hydrogen-deuterium exchange in deuterated water by heating to prepare a deuterated alkylating agent. The method has a simple process, a high yield, and can be prepared in large quantities at a ten-gram level. More importantly, the deuterated alkylating agent can be used as a free radical reagent in a free radical addition reaction to prepare different types of deuterated alkylated products, and has important application value. BRIEF DESCRIPTION OF THE DRAWINGS

[0069] Figure 1 The compound represented by formula VIII-1 in Example 16 of the present invention 1 H NMR spectrum.

[0070] Figure 2 The compound represented by formula VIII-1 in Example 16 of the present invention 13 C NMR spectrum. DETAILED DESCRIPTION

[0071] The present invention is further described in detail below in conjunction with specific embodiments, and the examples provided are only for illustrating the present invention, rather than for limiting the scope of the present invention. The examples provided below can be used as a guide for further improvements by those of ordinary skill in the art, and do not constitute a limitation of the present invention in any way.

[0072] The methods used in the following examples, unless otherwise specified, are conventional methods, and are carried out according to the techniques or conditions described in the literature in the art or according to the product instructions. The materials, reagents, etc. used in the following examples, unless otherwise specified, can be obtained from commercial sources. Nuclear magnetic resonance is measured by a Bruker nuclear magnetic resonance instrument. The abbreviations known to those skilled in the art represent the following 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, and then isopropyltriphenylphosphine iodide (1 mmol, 1.0 equiv.), potassium carbonate (1 mmol, 1 equiv.) and 1.0 ml of deuterated water were added and stirred at 100°C for 6 hours. The reaction solution was cooled, water was added and extracted three times with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and concentrated. After adding ether, it was filtered and separated to obtain the compound shown in I-1.

[0075]

[0076] The experimental data of the compound represented by formula I-1 are as follows: White solid. Yield: 0.72mmol, 311.8mg, 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] + Calculate for C 21 H 21 DP + :306.1516; found:306.1501. It was verified that the obtained compound was the compound represented by 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, and then isobutyltriphenylphosphine iodide (1 mmol, 1.0 equiv.), potassium carbonate (1 mmol, 1 equiv.) and 1.0 ml of deuterated water were added and stirred at 100°C for 6 hours. The reaction solution was cooled, water was added and extracted three times with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and concentrated. After adding ether, it was filtered and separated to obtain the compound shown in I-2.

[0079]

[0080] The experimental data of the compound represented by formula I-2 are as follows: White solid. Yield: 0.61mmol, 272.7mg, 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] + Calculate for C 22 H23 DP + :320.1673; found:320.1663. It was verified that the obtained compound was the compound represented by 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, and then cyclopentyltriphenylphosphine iodide (1 mmol, 1.0 equiv.), potassium carbonate (1 mmol, 1 equiv.) and 1.0 ml of deuterated water were added and stirred at 100°C for 6 hours. The reaction solution was cooled, water was added and extracted three times with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and concentrated. After adding ether, it was filtered and separated to obtain the compound shown in I-3.

[0083]

[0084] The experimental data of the compound represented by formula I-3 are as follows: White solid. Yield: 0.71mmol, 325.9mg, 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] + Calculate for C 23 H 23 DP + :332.1673; found:332.1664. It was verified that the obtained compound was the compound represented by 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, and then cyclopentyltriphenylphosphine iodide (1 mmol, 1.0 equiv.), potassium carbonate (1 mmol, 1 equiv.) and 1.0 ml of deuterated water were added and stirred at 100°C for 6 hours. The reaction solution was cooled, water was added and extracted three times with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and concentrated. After adding ether, it was filtered and separated to obtain the compound shown in I-4.

[0087]

[0088] The experimental data of the compound represented by formula I-4 are as follows: White solid. Yield: 0.64mmol, 302.7mg, 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] + Calculate for C 24 H 25 DP + :346.1829; found:346.1809. It was verified that the obtained compound was the compound represented by 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, and then isobutyltriphenylphosphine iodide (1 mmol, 1.0 equiv.), triethylamine (0.2 mmol, 0.2 equiv.) and 1.0 ml of deuterated water were added and stirred at 100°C for 6 hours. The reaction solution was cooled, water was added and extracted three times with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and concentrated. After adding ether, it was filtered and separated to obtain the compound shown in Ⅱ-1.

[0091]

[0092] The experimental data of the compound represented by 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] + Calculate for C 22 H 22 D2P + :321.1736; found:321.1721. It was verified that the obtained compound was the compound represented by 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 cooled to room temperature under vacuum, and then n-butyltriphenylphosphine iodide (1 mmol, 1.0 equiv.), potassium carbonate (1 mmol, 1 equiv.) and 1.0 ml of deuterated water were added and stirred at 100°C for 6 hours. The reaction solution was cooled, water was added and extracted three times with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and concentrated. After adding ether, it was filtered and separated to obtain the compound shown in Ⅱ-2.

[0095]

[0096] The experimental data of the compound represented by formula II-2 are as follows: White solid. Yield: 0.83mmol, 371.8mg, 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] + Calculate for C 22 H 22 D2P + :321.1736; found:321.1720. It was verified that the obtained compound was the compound represented by 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, and then isopentyltriphenylphosphine iodide (1 mmol, 1.0 equiv.), potassium carbonate (1 mmol, 1 equiv.) and 1.0 ml of deuterated water were added and stirred at 100°C for 6 hours. The reaction solution was cooled, water was added and extracted three times with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and concentrated. After adding ether, it was filtered and separated to obtain the compound shown in Ⅱ-3.

[0099]

[0100] The experimental data of the compound represented by formula II-3 are as follows: White solid. Yield: 0.66mmol, 304.9mg, 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] + Calculate for C 23 H 24 D2P + :335.1892; found:335.1876. It was verified that the obtained compound was the compound represented by 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 cooled to room temperature under vacuum, and then n-octyltriphenylphosphine iodide (1 mmol, 1.0 equiv.), potassium carbonate (1 mmol, 1 equiv.) and 1.0 ml of deuterated water were added and stirred at 100°C for 6 hours. The reaction solution was cooled, water was added and extracted three times with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and concentrated. After adding ether, it was filtered and separated to obtain the compound shown in Ⅱ-4.

[0103]

[0104] The experimental data of the compound represented by formula II-4 are as follows: white solid. Yield: 0.66mmol, 332.6mg, 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] + Calculate for C 26 H 30 D2P + :377.2362; found:377.2353. It was verified that the obtained compound was the compound represented by 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 cooled to room temperature under vacuum, and then cyclohexylmethyltriphenylphosphine iodide (1 mmol, 1.0 equiv.), potassium carbonate (1 mmol, 1 equiv.) and 1.0 ml of deuterated water were added and stirred at 100°C for 6 hours. The reaction solution was cooled, water was added and extracted three times with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and concentrated. After adding ether, it was filtered and separated to obtain the compound shown in Ⅱ-5.

[0107]

[0108] The experimental data of the compound represented by formula II-5 are as follows: white solid. Yield: 0.65mmol, 317.2mg, 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] + Calculate for C 25 H 26 D2P + :361.2049; found:361.2036. It was verified that the obtained compound was the compound represented by 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, and then cyclopentylmethyltriphenylphosphine iodide (1 mmol, 1.0 equiv.), triethylamine (0.2 mmol, 0.2 equiv.) and 1.0 ml of deuterated water were added and stirred at 100°C for 6 hours. The reaction solution was cooled, water was added and extracted three times with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and concentrated. After adding ether, it was filtered and separated to obtain the compound shown in II-6.

[0111]

[0112] The experimental data of the compound represented by formula II-6 are as follows: White solid. Yield: 0.71mmol, 336.5mg, 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] + Calculate for C 24 H 24 D2P + :347.1892; found:347.1884. It was verified that the obtained compound was the compound represented by 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, and then 3,3,3-trifluoropropyltriphenylphosphine iodide (1 mmol, 1.0 equiv.), triethylamine (0.2 mmol, 0.2 equiv.) and 1.0 ml of deuterated water were added and stirred at 100°C for 6 hours. The reaction solution was cooled, water was added and extracted three times with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and concentrated. After adding ether, it was filtered and separated to obtain the compound shown in Ⅱ-7.

[0115]

[0116] The experimental data of the compound represented by formula II-7 are as follows: White solid. Yield: 0.75mmol, 366.0mg, 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] + Calculate for C 21 H 17 D2F3P+ :361.1297; found:361.1288. It was verified that the obtained compound was the compound represented by 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, and then 3,3,3-trifluorobutyltriphenylphosphine iodide (1 mmol, 1.0 equiv.), triethylamine (0.2 mmol, 0.2 equiv.) and 1.0 ml of deuterated water were added and stirred at 100°C for 6 hours. The reaction solution was cooled, water was added and extracted three times with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and concentrated. After adding ether, it was filtered and separated to obtain the compound shown in II-8.

[0119]

[0120] The experimental data of the compound represented by formula II-8 are as follows: White solid. Yield: 0.71mmol, 356.4mg, 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] + Calculate for C 22 H 19 D2F3P + :375.1453; found:375.1444. It was verified that the obtained compound was the compound represented by 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 cooled to room temperature under vacuum, and then phenylethyltriphenylphosphine iodide (1 mmol, 1.0 equiv.), triethylamine (0.2 mmol, 0.2 equiv.) and 1.0 ml of deuterated water were added and stirred at 100°C for 6 hours. The reaction solution was cooled, water was added and extracted three times with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and concentrated. After adding ether, it was filtered and separated to obtain the compound shown in II-9.

[0123]

[0124] The experimental data of the compound represented by formula II-9 are as follows: White solid. Yield: 0.61mmol, 302.6mg, 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] + Calculate for C 26 H 22 D2P + :369.1736; found:369.1726. It was verified that the obtained compound was the compound represented by 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 cooled to room temperature under vacuum, and then phenylpropyltriphenylphosphine iodide (1 mmol, 1.0 equiv.), potassium carbonate (1 mmol, 1 equiv.) and 1.0 ml of deuterated water were added and stirred at 100°C for 6 hours. The reaction solution was cooled, water was added and extracted three times with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and concentrated. After adding ether, it was filtered and separated to obtain the compound shown in Ⅱ-10.

[0127]

[0128] The experimental data of the compound represented by formula II-10 are as follows: White solid. Yield: 0.73mmol, 372.3mg, 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] + Calculate for C 27 H 24 D2P + :383.1892; found:383.1878. It was verified that the obtained compound was the compound represented by 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, and then 1-butenyltriphenylphosphine iodide (1 mmol, 1.0 equiv.), triethylamine (0.2 mmol, 0.2 equiv.) and 1.0 ml of deuterated water were added and stirred at 100°C for 6 hours. The reaction solution was cooled, water was added and extracted three times with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and concentrated. After adding ether, it was filtered and separated to obtain the compound shown in Ⅱ-11.

[0131]

[0132] The experimental data of the compound represented by formula II-11 are as follows: White solid. Yield: 0.72mmol, 321.1mg, 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] + Calculate for C 22 H 20 D2P + :319.1579; found:319.1567. It was verified that the obtained compound was the compound represented by formula II-11.

[0133] Example 16: Synthesis of the compound represented by formula VIII-1

[0134] The reaction tube dried in advance was cooled to room temperature under vacuum, and a deuterated alkylating agent (the compound of formula I-1 prepared in Example 1) (0.2 mmol, 2.0 equiv.), ene amide of formula Va (0.1 mmol, 1.0 equiv.), tetramethylguanidine (0.2 mmol, 2.0 equiv.), 0.2 ml of anhydrous N, N-dimethylacetamide (DMA) and 0.8 ml of anhydrous toluene were added in a glove box, and the mixture was moved to 450 nm blue light for irradiation and stirred at 35 ° C until the thin layer chromatography control showed that the ene amide disappeared (36 hours), and 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 a compound of formula VIII-1.

[0135]

[0136] The experimental data of the compound represented by formula VIII-1 are as follows: Yellow oil.Yield: 0.082mmol, 17.9mg, 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] + Calculate for C 14 H 19 DNO + :219.1602; found:219.1597. 1 H NMR spectrum see Figure 1 , 13 C NMR spectrum see Figure 2 The structure was verified to be correct. It was verified that the obtained compound was the compound shown in formula VIII-1.

[0137] Example 17: Synthesis of the compound represented by formula VIII-2

[0138] The pre-dried reaction tube was cooled to room temperature under vacuum, and a deuterated alkylating agent (the compound of formula I-2 prepared in Example 2) (0.2 mmol, 2.0 equiv.), ene amide of formula Va (0.1 mmol, 1.0 equiv.), tetramethylguanidine (0.2 mmol, 2.0 equiv.), 0.2 ml of anhydrous N, N-dimethylacetamide (DMA) and 0.8 ml of anhydrous toluene were added in a glove box, and the mixture was moved to 450 nm blue light for irradiation and stirred at 35 ° C until the thin layer chromatography control showed that the ene amide disappeared (36 hours), and 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 a compound of formula VIII-2.

[0139]

[0140] The experimental data of the compound represented by 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] + Calculate for C 15 H 21 DNO + :233.1759; found:233.1748. It was verified that the obtained compound was the compound represented by formula VIII-2.

[0141] Example 18: Synthesis of the compound represented by formula VIII-3

[0142] The pre-dried reaction tube was cooled to room temperature under vacuum, and a deuterated alkylating agent (the compound of formula I-3 prepared in Example 3) (0.2 mmol, 2.0 equiv.), ene amide of formula Va (0.1 mmol, 1.0 equiv.), tetramethylguanidine (0.2 mmol, 2.0 equiv.), 0.2 ml of anhydrous N, N-dimethylacetamide (DMA) and 0.8 ml of anhydrous toluene were added in a glove box, and the mixture was moved to 450 nm blue light for irradiation and stirred at 35 ° C until the thin layer chromatography control showed that the ene amide disappeared (36 hours), and 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 a compound of formula VIII-3.

[0143]

[0144] The experimental data of the compound represented by 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] + Calculate for C 16 H 21 DNO + :245.1759; found:245.1750. It was verified that the obtained compound was the compound represented by 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, and a deuterated alkylating agent (the compound of formula I-4 prepared in Example 4) (0.2 mmol, 2.0 equiv.), ene amide of formula Va (0.1 mmol, 1.0 equiv.), tetramethylguanidine (0.2 mmol, 2.0 equiv.), 0.2 ml of anhydrous N, N-dimethylacetamide (DMA) and 0.8 ml of anhydrous toluene were added in a glove box, and the mixture was moved to 450 nm blue light for irradiation and stirred at 35 ° C until the thin layer chromatography control showed that the ene amide disappeared (36 hours), and 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 a compound of formula VIII-4.

[0147]

[0148] The experimental data of the compound represented by formula VIII-4 are as follows: Light yellow oil. Yield: 0.080mmol, 20.7mg, 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] + Calculate for C 17 H 23 DNO + :259.1915; found:259.1904. It was verified that the obtained compound was the compound represented by formula VIII-4.

[0149] Example 20: Synthesis of the compound represented by formula VIII'-1

[0150] The reaction tube dried in advance was cooled to room temperature under vacuum, and a deuterated alkylating agent (the compound of formula II-2 prepared in Example 6) (0.2 mmol, 2.0 equiv.), ene amide of formula Va (0.1 mmol, 1.0 equiv.), tetramethylguanidine (0.2 mmol, 2.0 equiv.), 0.2 ml of anhydrous N, N-dimethylacetamide (DMA) and 0.8 ml of anhydrous toluene were added in a glove box, and the mixture was moved to 450 nm blue light for irradiation and stirred at 35 ° C until the thin layer chromatography control showed that the ene amide disappeared (36 hours), and 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 a compound of formula VIII'-1.

[0151]

[0152] The experimental data of the compound represented by formula VIII'-1 are as follows: Light yellow oil. Yield: 0.090mmol, 21.0mg, 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] + Calculate for C 15 H 20 D2NO + :234.1821; found:234.1817. It was verified that the obtained compound was the compound represented by formula VIII'-1.

[0153] Example 21: Synthesis of the compound represented by formula VIII'-2

[0154] The reaction tube dried in advance was cooled to room temperature under vacuum, and a deuterated alkylating agent (the compound of formula II-4 prepared in Example 8) (0.2 mmol, 2.0 equiv.), ene amide of formula Va (0.1 mmol, 1.0 equiv.), tetramethylguanidine (0.2 mmol, 2.0 equiv.), 0.2 ml of anhydrous N, N-dimethylacetamide (DMA) and 0.8 ml of anhydrous toluene were added in a glove box, and the mixture was moved to 450 nm blue light for irradiation and stirred at 35 ° C until the thin layer chromatography control showed that the ene amide disappeared (36 hours), and 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 a compound of formula VIII'-2.

[0155]

[0156] The experimental data of the compound represented by formula VIII'-2 are as follows: Light yellow oil. Yield: 0.083mmol, 24.0mg, 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] + Calculate for C 19 H 28 D2NO + :290.2447; found:290.2437. It was verified that the obtained compound was the compound represented by formula VIII'-2.

[0157] Example 22: Synthesis of the compound represented by formula VIII'-3

[0158] The reaction tube dried in advance was cooled to room temperature under vacuum, and a deuterated alkylating agent (the compound of formula I-5 prepared in Example 5) (0.2 mmol, 2.0 equiv.), ene amide of formula Va (0.1 mmol, 1.0 equiv.), tetramethylguanidine (0.2 mmol, 2.0 equiv.), 0.2 ml of anhydrous N,N-dimethylacetamide (DMA) and 0.8 ml of anhydrous toluene were added in a glove box, and the mixture was irradiated under a 450 nm blue light and stirred at 35° C. until the thin layer chromatography control showed that the ene amide disappeared (36 hours), and 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 a compound of formula VIII'-3.

[0159]

[0160] The experimental data of the compound represented by formula VIII'-3 are as follows: Light yellow oil. Yield: 0.068mmol, 15.8mg, 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] + Calculate for C 15 H 20 D2NO + :234.1821; found:234.1817. It was verified that the obtained compound was the compound represented by formula VIII'-3.

[0161] Example 23: Synthesis of the compound represented by formula VIII'-4

[0162] The reaction tube dried in advance was cooled to room temperature under vacuum, and a deuterated alkylating agent (the compound of formula II-3 prepared in Example 7) (0.2 mmol, 2.0 equiv.), ene amide of formula Va (0.1 mmol, 1.0 equiv.), tetramethylguanidine (0.2 mmol, 2.0 equiv.), 0.2 ml of anhydrous N, N-dimethylacetamide (DMA) and 0.8 ml of anhydrous toluene were added in a glove box, and the mixture was moved to 450 nm blue light for irradiation and stirred at 35 ° C until the thin layer chromatography control showed that the ene amide disappeared (36 hours), and 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 a compound of formula VIII'-4.

[0163]

[0164] The experimental data of the compound represented by 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] + Calculate for C 16 H 22 D2NO+ :248.1978; found:248.1973. It was verified that the obtained compound was the compound represented by formula VIII'-4.

[0165] Example 24: Synthesis of the compound represented by formula VIII'-5

[0166] The pre-dried reaction tube was cooled to room temperature under vacuum, and a deuterated alkylating agent (the compound of formula II-6 prepared in Example 10) (0.2 mmol, 2.0 equiv.), ene amide of formula Va (0.1 mmol, 1.0 equiv.), tetramethylguanidine (0.2 mmol, 2.0 equiv.), 0.2 ml of anhydrous N, N-dimethylacetamide (DMA) and 0.8 ml of anhydrous toluene were added in a glove box, and the mixture was moved to 450 nm blue light for irradiation and stirred at 35 ° C until the thin layer chromatography control showed that the ene amide disappeared (36 hours), and 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 a compound of formula VIII'-5.

[0167]

[0168] The experimental data of the compound represented by formula VIII'-5 are as follows: Light yellow oil. Yield: 0.081mmol, 21.0mg, 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] + Calculate for C 17 H 22 D2NO +:260.1978; found:260.1962. It was verified that the obtained compound was the compound represented by formula VIII'-5.

[0169] Example 25: Synthesis of the compound represented by formula VIII'-6

[0170] The pre-dried reaction tube was cooled to room temperature under vacuum, and a deuterated alkylating agent (the compound of formula II-5 prepared in Example 9) (0.2 mmol, 2.0 equiv.), ene amide of formula Va (0.1 mmol, 1.0 equiv.), tetramethylguanidine (0.2 mmol, 2.0 equiv.), 0.2 ml of anhydrous N, N-dimethylacetamide (DMA) and 0.8 ml of anhydrous toluene were added in a glove box, and the mixture was moved to 450 nm blue light for irradiation and stirred at 35 ° C until the thin layer chromatography control showed that the ene amide disappeared (36 hours), and 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 a compound of formula VIII'-6.

[0171]

[0172] The experimental data of the compound represented by formula VIII'-6 are as follows: Light yellow oil. Yield: 0.078mmol, 21.3mg, 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] + Calculate for C 18 H 24 D2NO +:274.2134; found:274.2126. It was verified that the obtained compound was the compound represented by formula VIII'-6.

[0173] Example 26: Synthesis of the compound represented by formula VIII'-7

[0174] The pre-dried reaction tube was cooled to room temperature under vacuum, and a deuterated alkylating agent (the compound of formula II-11 prepared in Example 15) (0.2 mmol, 2.0 equiv.), ene amide of formula Va (0.1 mmol, 1.0 equiv.), tetramethylguanidine (0.2 mmol, 2.0 equiv.), 0.2 ml of anhydrous N,N-dimethylacetamide (DMA) and 0.8 ml of anhydrous toluene were added in a glove box. The reaction tube was moved under 450 nm blue light for irradiation and stirred at 35°C until the thin layer chromatography control showed the disappearance of ene amide (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 a compound of formula V-11.

[0175]

[0176] The experimental data of the compound represented by formula VIII'-7 are as follows: Light yellow oil. Yield: 0.072mmol, 16.6mg, 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] + Calculate for C 15 H 18 D2NO + :232.1665; found:232.1658. It was verified that the obtained compound was the compound represented by formula VIII'-7.

[0177] Example 27: Synthesis of the compound represented by formula VIII'-8

[0178] The pre-dried reaction tube was cooled to room temperature under vacuum, and a deuterated alkylating agent (the compound of formula II-9 prepared in Example 13) (0.2 mmol, 2.0 equiv.), ene amide of formula Va (0.1 mmol, 1.0 equiv.), tetramethylguanidine (0.2 mmol, 2.0 equiv.), 0.2 ml of anhydrous N,N-dimethylacetamide (DMA) and 0.8 ml of anhydrous toluene were added in a glove box. The reaction tube was moved to 450 nm blue light for irradiation and stirred at 35 ° C until the thin layer chromatography control showed that the ene amide disappeared (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 a compound of formula VIII'-8.

[0179]

[0180] The experimental data of the compound represented by formula VIII'-8 are as follows: Light yellow oil. Yield: 0.091mmol, 25.6mg, 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] + Calculate for C 19 H 20 D2NO + :282.1821; found:282.1812. It was verified that the obtained compound was the compound represented by formula VIII'-8.

[0181] Example 28: Synthesis of the compound represented by formula VIII'-9

[0182] The reaction tube dried in advance was cooled to room temperature under vacuum, and a deuterated alkylating agent (the compound of formula II-8 prepared in Example 12) (0.2 mmol, 2.0 equiv.), ene amide of formula Va (0.1 mmol, 1.0 equiv.), tetramethylguanidine (0.2 mmol, 2.0 equiv.), 0.2 ml of anhydrous N, N-dimethylacetamide (DMA) and 0.8 ml of anhydrous toluene were added in a glove box, and the mixture was moved to 450 nm blue light for irradiation and stirred at 35 ° C until the thin layer chromatography control showed that the ene amide disappeared (36 hours), and 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 a compound of formula VIII'-9.

[0183]

[0184] The experimental data of the compound represented by formula VIII'-9 are as follows: Light yellow oil. Yield: 0.076mmol, 21.8mg, 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] + Calculate for C 15 H 17 D2NOF3 + :288.1539; found:288.1525. It was verified that the obtained compound was the compound represented by formula VIII'-9.

[0185] Example 29: Synthesis of the compound represented by formula VIII'-10

[0186] The pre-dried reaction tube was cooled to room temperature under vacuum, and a deuterated alkylating agent (the compound of formula II-7 prepared in Example 11) (0.2 mmol, 2.0 equiv.), ene amide of formula Va (0.1 mmol, 1.0 equiv.), tetramethylguanidine (0.2 mmol, 2.0 equiv.), 0.2 ml of anhydrous N,N-dimethylacetamide (DMA) and 0.8 ml of anhydrous toluene were added in a glove box, and the mixture was irradiated under a 450 nm blue light and stirred at 35° C. until the thin layer chromatography control showed that the ene amide disappeared (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 a compound of formula VIII'-10.

[0187]

[0188] The experimental data of the compound represented by formula VIII'-10 are as follows: Light yellow oil.Yield: 0.070mmol, 19.1mg, 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] + Calculate for C 14 H 15 D2NOF3 + :274.1382; found:274.1375. It was verified that the obtained compound was the compound represented by formula VIII'-10.

[0189] Example 30: Synthesis of the compound represented by formula IX-1

[0190] The pre-dried reaction tube was cooled to room temperature under vacuum, and a deuterated alkylating agent (the compound of formula I-2 prepared in Example 2) (0.1 mmol, 1.0 equiv.), an olefin of formula VI (0.2 mmol, 2.0 equiv.), tetramethylguanidine (0.2 mmol, 2.0 equiv.), deuterated water (0.3 mmol, 3.0 equiv.) and 1.0 ml of anhydrous dimethyl sulfoxide (DMSO) were added in a glove box. The mixture was moved to 450 nm blue light for irradiation and stirred at 35 ° C until the thin layer chromatography control showed the disappearance of the ene amide (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 a compound of formula IX-1.

[0191]

[0192] The experimental data of the compound represented by 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] + Calculate for C 21 H 21 D N2O + :342.1678; found:342.1687. It was verified that the obtained compound was the compound represented by formula IX-1.

[0193] Example 31: Synthesis of the compound represented by formula IX-2

[0194] The reaction tube dried in advance was cooled to room temperature under vacuum, and a deuterated alkylating agent (the compound of formula I-1 prepared in Example 1) (0.1 mmol, 1.0 equiv.), an olefin of formula VI (0.2 mmol, 2.0 equiv.), tetramethylguanidine (0.2 mmol, 2.0 equiv.), deuterated water (0.3 mmol, 3.0 equiv.) and 1.0 ml of anhydrous dimethyl sulfoxide (DMSO) were added in a glove box, and the mixture was moved to 450 nm blue light for irradiation and stirred at 35 ° C until the thin layer chromatography control showed the disappearance of the ene amide (36 hours), and 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 a compound of formula IX-2.

[0195]

[0196] The experimental data of the compound represented by formula IX-2 are as follows: Light yellow oil. Yield: 0.072mmol, 22.0mg, 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] + Calculate for C 20 H 19 D N2O + :328.1521; found:328.1531. It was verified that the obtained compound was the compound represented by formula IX-2.

[0197] Example 32: Synthesis of the compound represented by formula IX-3

[0198] The reaction tube dried in advance was cooled to room temperature under vacuum, and a deuterated alkylating agent (the compound of formula I-3 prepared in Example 3) (0.1 mmol, 1.0 equiv.), an olefin of formula VI (0.2 mmol, 2.0 equiv.), tetramethylguanidine (0.2 mmol, 2.0 equiv.), deuterated water (0.3 mmol, 3.0 equiv.) and 1.0 ml of anhydrous dimethyl sulfoxide (DMSO) were added in a glove box, and the mixture was irradiated under a 450 nm blue light and stirred at 35° C. until the thin layer chromatography control showed the disappearance of the ene amide (36 hours), and 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 a compound of formula IX-3.

[0199]

[0200] The experimental data of the compound represented by formula IX-3 are as follows: Light yellow oil. Yield: 0.073mmol, 24.1mg, 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] + Calculate for C 22 H 21 D N2O + :354.1677; found:354.1687. It was verified that the obtained compound was the compound represented by formula IX-3.

[0201] Example 33: Synthesis of the compound represented by formula IX'-1

[0202] The reaction tube dried in advance was cooled to room temperature under vacuum, and a deuterated alkylating agent (the compound of formula II-2 prepared in Example 6) (0.1 mmol, 1.0 equiv.), an olefin of formula VI (0.2 mmol, 2.0 equiv.), tetramethylguanidine (0.2 mmol, 2.0 equiv.), deuterated water (0.3 mmol, 3.0 equiv.) and 1.0 ml of anhydrous dimethyl sulfoxide (DMSO) were added in a glove box. The mixture was moved to 450 nm blue light for irradiation and stirred at 35 ° C until the thin layer chromatography control showed the disappearance of the ene amide (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 a compound of formula IX'-1.

[0203]

[0204] The experimental data of the compound represented by formula IX'-1 are as follows: Colorless oil.Yield: 0.069mmol, 22.1mg, 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] + Calculate for C 21 H 20 D2N2O + :343.1740; found:343.1750. It was verified that the obtained compound was the compound represented by formula IX'-1.

[0205] Example 34: Synthesis of the compound represented by formula IX'-2

[0206] The reaction tube dried in advance was cooled to room temperature under vacuum, and a deuterated alkylating agent (the compound of formula II-4 prepared in Example 8) (0.1 mmol, 1.0 equiv.), an olefin of formula VI (0.2 mmol, 2.0 equiv.), tetramethylguanidine (0.2 mmol, 2.0 equiv.), deuterated water (0.3 mmol, 3.0 equiv.) and 1.0 ml of anhydrous dimethyl sulfoxide (DMSO) were added in a glove box. The mixture was moved to 450 nm blue light for irradiation and stirred at 35 ° C until the thin layer chromatography control showed the disappearance of the ene amide (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 a compound of formula IX'-2.

[0207]

[0208] The experimental data of the compound represented by formula IX'-2 are as follows: Colorless oil.Yield: 0.058mmol, 21.8mg, 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] + Calculate for C 25 H 28 D2N2O + :399.2365; found:399.2376. It was verified that the obtained compound was the compound represented by formula IX'-2.

[0209] Example 35: Synthesis of the compound represented by formula IX'-3

[0210] The reaction tube dried in advance was cooled to room temperature under vacuum, and a deuterated alkylating agent (the compound of formula II-1 prepared in Example 5) (0.1 mmol, 1.0 equiv.), an olefin of formula VI (0.2 mmol, 2.0 equiv.), tetramethylguanidine (0.2 mmol, 2.0 equiv.), deuterated water (0.3 mmol, 3.0 equiv.) and 1.0 ml of anhydrous dimethyl sulfoxide (DMSO) were added in a glove box, and the mixture was irradiated under a 450 nm blue light and stirred at 35° C. until the thin layer chromatography control showed the disappearance of the ene amide (36 hours), and 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 a compound of formula IX'-3.

[0211]

[0212] The experimental data of the compound represented by formula IX'-3 are as follows: Colorless oil.Yield: 0.050mmol, 16.0mg, 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] + Calculate for C 19 H 16 D2N2O +:343.1739; found:343.1750. It was verified that the obtained compound was the compound represented by formula IX'-3.

[0213] Example 36: Synthesis of the compound represented by formula IX'-4

[0214] The reaction tube dried in advance was cooled to room temperature under vacuum, and a deuterated alkylating agent (the compound of formula II-6 prepared in Example 10) (0.1 mmol, 1.0 equiv.), an olefin of formula VI (0.2 mmol, 2.0 equiv.), tetramethylguanidine (0.2 mmol, 2.0 equiv.), deuterated water (0.3 mmol, 3.0 equiv.) and 1.0 ml of anhydrous dimethyl sulfoxide (DMSO) were added in a glove box. The mixture was moved to 450 nm blue light for irradiation and stirred at 35 ° C until the thin layer chromatography control showed the disappearance of the ene amide (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 a compound of formula IX'-4.

[0215]

[0216] The experimental data of the compound represented by formula IX'-4 are as follows: Colorless oil.Yield: 0.052mmol, 18.0mg, 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] +Calculate for C 23 H 22 D2N2O + :369.1895; found:369.1906. It was verified that the obtained compound was the compound represented by formula IX'-4.

[0217] Example 37: Synthesis of the compound represented by formula IX'-5

[0218] The pre-dried reaction tube was cooled to room temperature under vacuum, and a deuterated alkylating agent (the compound of formula II-5 prepared in Example 9) (0.1 mmol, 1.0 equiv.), an olefin of formula VI (0.2 mmol, 2.0 equiv.), tetramethylguanidine (0.2 mmol, 2.0 equiv.), deuterated water (0.3 mmol, 3.0 equiv.) and 1.0 ml of anhydrous dimethyl sulfoxide (DMSO) were added in a glove box. The mixture was moved to 450 nm blue light for irradiation and stirred at 35 ° C until the thin layer chromatography control showed the disappearance of the ene amide (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 a compound of formula IX'-5.

[0219]

[0220] The experimental data of the compound represented by 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] + Calculate for C 24 H 24 D2N2O + :383.2052; found:383.2063. It was verified that the obtained compound was the compound represented by formula IX'-5.

[0221] Example 38: Synthesis of the compound represented by formula IX'-6

[0222] The reaction tube dried in advance was cooled to room temperature under vacuum, and a deuterated alkylating agent (the compound of formula II-10 prepared in Example 14) (0.1 mmol, 1.0 equiv.), an olefin of formula VI (0.2 mmol, 2.0 equiv.), tetramethylguanidine (0.2 mmol, 2.0 equiv.), deuterated water (0.3 mmol, 3.0 equiv.) and 1.0 ml of anhydrous dimethyl sulfoxide (DMSO) were added in a glove box. The mixture was moved to 450 nm blue light for irradiation and stirred at 35 ° C until the thin layer chromatography control showed the disappearance of the ene amide (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 a compound of formula IX'-6.

[0223]

[0224] The experimental data of the compound represented by formula IX'-6 are as follows: White solid. Yield: 0.055mmol, 21.0mg, 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] + Calculate for C 26 H 22 D2N2O + :405.1895; found:405.1906. It was verified that the obtained compound was the compound represented by formula IX'-6.

[0225] Example 39: Synthesis of the compound represented by formula IX'-7

[0226] The reaction tube dried in advance was cooled to room temperature under vacuum, and a deuterated alkylating agent (the compound of formula II-8 prepared in Example 12) (0.1 mmol, 1.0 equiv.), an olefin of formula VI (0.2 mmol, 2.0 equiv.), tetramethylguanidine (0.2 mmol, 2.0 equiv.), deuterated water (0.3 mmol, 3.0 equiv.) and 1.0 ml of anhydrous dimethyl sulfoxide (DMSO) were added in a glove box. The mixture was moved to 450 nm blue light for irradiation and stirred at 35 ° C until the thin layer chromatography control showed the disappearance of the ene amide (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 a compound of formula IX'-7.

[0227]

[0228] The experimental data of the compound represented by formula IX'-7 are as follows: Colorless oil.Yield: 0.059mmol, 22.1mg, 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] + Calculate for C 21 H 18 D2N2F3O + :375.1648; found:375.1638. It was verified that the obtained compound was the compound represented by formula IX'-7.

[0229] Example 40: Synthesis of the compound represented by formula X-1

[0230] The pre-dried reaction tube was cooled to room temperature under vacuum, and a deuterated alkylating agent (the compound of formula I-1 prepared in Example 1) (0.1 mmol, 1.0 equiv.), 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 in a glove box. The mixture was moved to 450 nm blue light for irradiation and stirred at 35 ° C until the thin layer chromatography control showed the disappearance of the ene amide (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 a compound of formula X-1.

[0231]

[0232] The experimental data of the compound represented by formula X-1 are as follows: Colorless oil. Yield: 0.072mmol, 16.0mg, 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] + Calculate for C 16 H 14 DNa + :245.1160; found:245.1152. It was verified that the obtained compound was the compound represented by formula X-1.

[0233] Example 41: Synthesis of the compound represented by formula X-2

[0234] The reaction tube dried in advance was cooled to room temperature under vacuum, and a deuterated alkylating agent (the compound of formula I-2 prepared in Example 2) (0.1 mmol, 1.0 equiv.), 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 in a glove box, and the mixture was irradiated under a 450 nm blue light and stirred at 35° C. until the thin layer chromatography control showed the disappearance of the ene amide (36 hours), and 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 a compound of formula X-2.

[0235]

[0236] The experimental data of the compound represented by formula X-2 are as follows: Colorless oil. Yield: 0.077mmol, 18.2mg, 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] + Calculate for C 17 H 17 DN + :237.1497; found:237.1487. It was verified that the obtained compound was the compound represented by formula X-2.

[0237] Example 42: Synthesis of the compound represented by formula X'-1

[0238] The pre-dried reaction tube was cooled to room temperature under vacuum, and a deuterated alkylating agent (the compound of formula II-2 prepared in Example 6) (0.1 mmol, 1.0 equiv.), 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 in a glove box. The mixture was moved to 450 nm blue light for irradiation and stirred at 35 ° C until the thin layer chromatography control showed the disappearance of the ene amide (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 a compound of formula X'-1.

[0239]

[0240] The experimental data of the compound represented by formula X'-1 are as follows: Colorless oil.Yield: 0.067mmol, 15.9mg, 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] + Calculate for C 17 H 15 D2N + :260.1379; found:260.1371. It was verified that the obtained compound was the compound represented by formula X'-1.

[0241] Example 43: Synthesis of the compound represented by formula X'-2

[0242] The pre-dried reaction tube was cooled to room temperature under vacuum, and a deuterated alkylating agent (the compound of formula II-6 prepared in Example 10) (0.1 mmol, 1.0 equiv.), 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 in a glove box. The mixture was irradiated under a 450 nm blue light and stirred at 35° C. until the thin layer chromatography control showed the disappearance of the ene amide (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 a compound of formula X'-2.

[0243]

[0244] The experimental data of the compound represented by formula X'-2 are as follows: Colorless oil.Yield: 0.092mmol, 24.2mg, 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] + Calculate for C 19 H 18 D2N + :264.1716; found:264.1707. It was verified that the obtained compound was the compound represented by formula X'-2.

[0245] Example 44: Synthesis of the compound represented by formula X'-3

[0246] The pre-dried reaction tube was cooled to room temperature under vacuum, and a deuterated alkylating agent (the compound of formula II-11 prepared in Example 15) (0.1 mmol, 1.0 equiv.), 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 in a glove box. The tube was moved to 450 nm blue light for irradiation and stirred at 35 ° C until the thin layer chromatography control showed the disappearance of the ene amide (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 a compound of formula VII-5.

[0247]

[0248] The experimental data of the compound represented by formula X'-3 are as follows: Colorless oil.Yield: 0.071mmol, 16.7mg, 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] + Calculate for C 17 H 14 D2N + :236.1403; found:236.1396. It was verified that the obtained compound was the compound represented by formula X'-3.

[0249] Example 45: Synthesis of the compound represented by formula X'-4

[0250] The pre-dried reaction tube was cooled to room temperature under vacuum, and a deuterated alkylating agent (the compound of formula II-9 prepared in Example 13) (0.1 mmol, 1.0 equiv.), 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 in a glove box. The mixture was irradiated under a 450 nm blue light and stirred at 35° C. until the thin layer chromatography control showed the disappearance of the ene amide (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 a compound of formula X'-4.

[0251]

[0252] The experimental data of the compound represented by formula X'-4 are as follows: White solid. Yield: 0.084mmol, 23.9mg, 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] + Calculate for C 21 H 15 D2N + :308.1379; found:308.1366. It was verified that the obtained compound was the compound represented by formula X'-4.

[0253] Example 46: Synthesis of the compound represented by formula X'-5

[0254] The pre-dried reaction tube was cooled to room temperature under vacuum, and a deuterated alkylating agent (the compound of formula II-10 prepared in Example 14) (0.1 mmol, 1.0 equiv.), 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 in a glove box. The tube was moved to 450 nm blue light for irradiation and stirred at 35 ° C until the thin layer chromatography control showed the disappearance of the ene amide (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 a compound of formula X'-5.

[0255]

[0256] The experimental data of the compound represented by formula X'-5 are as follows: White solid. Yield: 0.071mmol, 21.2mg, 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] + Calculate for C 22 H 17 D2N + :322.1535; found:322.1525. It was verified that the obtained compound was the compound represented by formula X'-5.

[0257] Example 47: Synthesis of the compound represented by formula X'-6

[0258] The pre-dried reaction tube was cooled to room temperature under vacuum, and a deuterated alkylating agent (the compound of formula II-8 prepared in Example 12) (0.1 mmol, 1.0 equiv.), 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 in a glove box. The mixture was moved to 450 nm blue light for irradiation and stirred at 35 ° C until the thin layer chromatography control showed the disappearance of the ene amide (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 a compound of formula X'-6.

[0259]

[0260] The experimental data of the compound represented by formula X'-6 are as follows: White solid. Yield: 0.090mmol, 18.1mg, 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) δ160.1, 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] + Calculate for C 17 H 13 D2NF3 + :292.1277; found:292.1267. It was verified that the obtained compound was the compound represented by formula X'-6.

[0261] The present invention has been described in detail above. For those skilled in the art, without departing from the purpose and scope of the present invention, can implement the present invention in a wider range under equivalent parameters, concentrations and conditions. Although the present invention provides specific embodiments, it should be understood that the present invention can be further improved. In a word, according to the principle of the present invention, the application is intended to include any changes, uses or improvements to the present invention, including departing from the disclosed scope in the application and the changes made with conventional techniques known in the art.

Claims

1. A compound represented by formula I or formula II, In Formula I to Formula II, R 1 , R 2 are each independently selected from hydrogen, C1-C7 alkyl, phenyl, benzyl, alkenyl or trifluoromethyl substituted alkyl; or, R 1 , R 2 Form a C3-C8 cycloalkyl group with the carbon on the main chain; R 3 The group selected from C1-C7 alkyl, C3-C8 cycloalkyl, phenyl, phenyl-substituted alkyl, benzyl, alkenyl, alkenyl-substituted alkyl or trifluoromethyl-substituted alkyl.

2. A method for synthesizing a compound of formula I or formula II, comprising the following steps: In the presence of a base, the compound represented by formula III or IV is heated in deuterated water to perform a hydrogen-deuterium exchange reaction to obtain a compound represented by formula I or II; In formula III to formula IV, R 1 , R 2 , R 3 The definitions of are the same as those of Formula I to Formula II.

3. The synthesis method according to claim 2, characterized in that: The feeding ratio of the compound represented by formula III or formula IV to deuterated water is 1 mmol:1.0 mL; The base is triethylamine or potassium carbonate, the molar ratio of the compound represented by formula III or formula IV to triethylamine is 1:(0.2-1), and the molar ratio of the compound represented by formula III or formula IV to potassium carbonate is 1:(0.5-2); The temperature of the hydrogen-deuterium exchange reaction is 60 to 110° C. and the time is 3 to 12 hours; The hydrogen-deuterium exchange reaction is carried out under vacuum conditions.

4. Use of the compound represented by formula I or formula II as a free radical deuterated alkylation reagent in the preparation of deuterated alkylation products.

5. A method for synthesizing a compound represented by formula VIII or formula VIII', comprising the following steps: In the presence of a base, the compound represented by formula I or formula II reacts with the compound represented by formula V in an organic solvent under visible light to obtain a compound represented by formula VIII or formula VIII'; In Formula VIII, R 1 , R 2 The definition of is the same as that of formula I; In Formula VIII', R 3 The definition of is the same as that of formula II; In Formula V, Formula VIII and Formula VIII', R 4 It is methyl, ethyl, phenyl or benzyl.

6. The synthesis method according to claim 5, characterized in that: The molar ratio of the compound represented by formula I or formula II to the compound represented by formula V is (1.5-3):1; The molar ratio of the compound represented by formula I or formula II to the base 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, ether, chloroform, dichloromethane, 1,2-dichloroethane, ethyl acetate, acetone, acetonitrile, N,N-dimethylformamide and N,N-dimethylformamide; The visible light is 450nm wavelength blue light; The reaction temperature is 30-40° C. and the reaction time is 24-48 hours.

7. A method for synthesizing a compound represented by formula IX or formula IX', comprising the following steps: In the presence of a base, the compound represented by formula I or formula II reacts with the compound represented by formula VI in deuterated water and an organic solvent under visible light to obtain a compound represented by formula IX or formula IX'; In the VIX formula, R 1 , R 2 The definition of is the same as that of formula I; In Formula IX, R 3 The definition of is the same as that of formula II.

8. The synthesis method according to claim 7, characterized in that: The molar ratio of the compound represented by formula I or formula II to the compound represented by formula VI is 1:(1-3); The molar ratio of the compound represented by formula I or formula II to the base is 1:(0.5-3); 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 molar ratio of the deuterated water to the compound represented by formula I or formula II is (1-6):1; The organic solvent is selected from at least one of toluene, xylene, chlorobenzene, benzene, dioxane, tetrahydrofuran, ether, chloroform, dichloromethane, dimethyl sulfoxide, 1,2-dichloroethane, ethyl acetate, acetone, acetonitrile, N,N-dimethylformamide and N,N-dimethylformamide; The visible light is 450nm wavelength blue light; The reaction temperature is 30-40° C. and the reaction time is 24-48 hours.

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

10. The synthesis method according to claim 9, characterized in that: The molar ratio of the compound represented by formula I or formula II to the compound represented by formula VII is 1:(1-3); The molar ratio of the compound represented by formula I or formula II to the base 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, ether, chloroform, dichloromethane, 1,2-dichloroethane, dimethyl sulfoxide, ethyl acetate, acetone, acetonitrile, N,N-dimethylformamide and N,N-dimethylformamide; The visible light is 450nm wavelength blue light; The reaction temperature is 30-40° C. and the reaction time is 24-48 hours.

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