Method for selectively and quantitatively reducing deuterated quinoline through nickel catalysis sites

Abstract

The invention provides a method for selectively and quantitatively reducing deuterated quinoline through nickel catalysis sites, and belongs to the technical field of organic synthesis. The deuterated quinoline heterocyclic compound is obtained by mixing materials including a quinoline heterocyclic compound, a nickel catalyst, a ligand, a boron deuteride / hydroboron and a deuterium source / hydrogen source in an organic solvent and reacting under an illumination condition. According to the present invention, the chemical synthesis of the quinoline heterocyclic compound 2-, 3-and 4-site mono-, di-or trideuterated hydroquinoline is achieved through the nickel catalysis and the simple deuterated reagent, the reaction condition is simple, the used raw material reagent is less, the regioselectivity, the multiple controllability, the step economy and the atom economy are provided, the substrate functional group compatibility is good, and the preparation method is suitable for the industrial production of the quinoline heterocyclic compound 2-, 3-and 4-site mono-, di-or trideuterated hydroquinoline. The product can be further converted into complex functional molecules; the deuterium-doped quinoline heterocyclic compound product with an excellent position can be obtained with high yield, and the method can be widely applied to synthesis of drug molecules of selective deuterated quinoline analogues.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, specifically to a method for the selective quantitative reduction of deuterated quinoline at a nickel catalytic site. Background Technology

[0002] The selective deuteration reduction of quinolines to generate deuterated 1,2,3,4-tetrahydroquinoline skeletons offers a powerful strategy for drug development, mechanism studies, and the synthesis of isotope-labeled standards. While numerous deuteration reduction methods exist, they primarily produce fully deuterated quinolines, lacking control over regioselectivity and deuterium content.

[0003] Based on this, the present invention provides a method for synthesizing mono-, di-, or tri-deuterated tetrahydroquinoline using simple deuterating reagents. Summary of the Invention

[0004] To address the shortcomings of existing technologies, this invention provides a nickel-catalyzed method for the selective quantitative reduction of deuterated quinolines. This invention employs nickel catalysis and strategically combines it with nucleophilic and / or electrophilic deuterium sources to achieve the chemical synthesis of mono-, di-, or tri-deuterated tetrahydroquinolines at the 2-, 3-, and 4- positions of quinoline heterocyclic compounds using simple deuterating reagents. This method exhibits regioselectivity and multiple controllability, while also possessing broad functional group compatibility. This method yields deuterated quinoline heterocyclic compound products with excellent positions in high yields and can be widely applied to the synthesis of drug molecules containing selectively deuterated quinoline analogs.

[0005] To achieve the above objectives, the specific technical solution of the present invention is as follows:

[0006] A method for selective quantitative reduction of deuterated quinoline by a nickel catalyst includes the following steps: mixing materials comprising a quinoline heterocyclic compound, a nickel catalyst, a ligand, a borodeuteride / borohydride, and a deuterium source / hydrogen source in an organic solvent, and reacting under light irradiation to obtain a deuterated quinoline heterocyclic compound, as shown in one of the following reaction equations:

[0007] (1) ;

[0008] (2) ;

[0009] (3) ;

[0010] (4) ;

[0011] In the formula, R and R' are each independently selected from at least one of hydrogen, halogen, cyano, hydroxyl, trifluoromethyl, alkyl, alkoxy, aryloxy, acyloxy, ester, acyl, thiophene, oxazolyl, substituted or unsubstituted phenyl, amide, and substituted or unsubstituted benzophenyl. The substituents of the phenyl or benzophenyl are each independently selected from at least one of halogen, cyano, hydroxyl, trifluoromethyl, alkyl, alkoxy, aryloxy, acyloxy, ester, acyl, thiophene, oxazolyl, and amide. The halogen includes fluorine, chlorine, bromine, or iodine.

[0012] Furthermore, the molar ratio of the quinoline heterocyclic compound, nickel catalyst, ligand, borodeuteride / borohydride, and deuterium source / hydrogen source is 1:(0.05~1):(0.05~1):(0.8~3):(0.5~3).

[0013] Furthermore, the nickel catalyst is selected from at least one of [1,1′-bis(diphenylphosphine)ferrocene] nickel dichloride (Ni(dppf)Cl2), nickel iodide (NiI2), nickel chloride (NiCl2), nickel bromide (NiBr2), nickel carbonate (NiCO3), bis-(1,5-cyclooctadiene) nickel (Ni(cod)2), and nickel trifluoromethanesulfonate (Ni(OTf)2).

[0014] Further, the borodeuteride is selected from at least one of sodium borodeuteride (NaBD4), lithium borodeuteride (LiBD4), sodium cyanoborodeuteride (NaBD3CN), and sodium triethylborodeuteride (NaBDEt3). In one example of the present invention, the borodeuteride is sodium borodeuteride.

[0015] Further, the borohydride is selected from at least one of sodium borohydride (NaBH4), lithium borohydride (LiBH4), sodium cyanoborohydride (NaBH3CN), and sodium triethylborohydride (NaBHEt3). In one example of the present invention, the borohydride is sodium borohydride.

[0016] Furthermore, the ligand is selected from at least one of the following structures:

[0017] .

[0018] Furthermore, the deuterium source is selected from deuterated hydrochloric acid (DCl), deuterated ethanol (EtOD), and deuterated tert-butanol (D&D). t At least one of BuOD, deuterated phosphoric acid (D3PO4), and deuterated boric acid (B(OD)3).

[0019] Furthermore, the hydrogen source is 2,2,3,3,4,4,5,5-octafluoropentanol.

[0020] Furthermore, the quinoline heterocyclic compound is selected from one of the following structures:

[0021] .

[0022] Furthermore, the organic solvent is selected from acetonitrile and / or tetrahydrofuran.

[0023] Furthermore, the wavelength of the illumination is 365~450 nm.

[0024] Furthermore, the reaction temperature is 10~75 °C.

[0025] More preferably, the reaction temperature is 20~35 °C.

[0026] Furthermore, materials including quinoline heterocyclic compounds, nickel catalysts, ligands, borodeuterides, and deuterium sources are mixed in an organic solvent and reacted under light irradiation to obtain deuterated quinoline heterocyclic compounds -d3. The reaction equation is as follows:

[0027] ,or .

[0028] Furthermore, the deuterated quinoline heterocyclic compound -d3 is selected from one of the following structures:

[0029] .

[0030] Furthermore, materials including quinoline heterocyclic compounds, nickel catalysts, ligands, borodeuterides, and hydrogen sources are mixed in an organic solvent and reacted under light irradiation to obtain deuterated quinoline heterocyclic compounds -d2. One of the reaction equations is shown below:

[0031] (1) ;

[0032] (2) ;

[0033] (3) ;

[0034] (4) .

[0035] Furthermore, the deuterated quinoline heterocyclic compound -d2 is selected from one of the following structures:

[0036] .

[0037] Furthermore, materials including quinoline heterocyclic compounds, nickel catalysts, ligands, borohydrides, and deuterium sources are mixed in an organic solvent and reacted under light irradiation to obtain deuterated quinoline heterocyclic compounds -d1. The reaction equation is as follows:

[0038] ,or .

[0039] Furthermore, the deuterated quinoline heterocyclic compound -d1 is selected from one of the following structures:

[0040] .

[0041] Furthermore, the material also includes potassium persulfate (K2S2O8), with a molar amount 1 to 3 times that of quinoline heterocyclic compounds.

[0042] The present invention also provides the application of the method in the deuteration modification of drug molecules.

[0043] Compared with the prior art, the advantages of the present invention are:

[0044] This invention uses quinoline heterocyclic compounds and borohydrides / boron deuterides as main raw materials to achieve site-selective quantitative deuteration of quinoline heterocyclic compounds via nickel catalysis. The reaction conditions of this invention are mild, and the raw materials and reagents used are few, exhibiting both step economy and atom economy. Furthermore, the substrate functional groups have good compatibility, which is beneficial for further converting the products into complex functional molecules, laying the foundation for the synthesis of drug molecules of selectively deuterated quinoline analogs. Detailed Implementation

[0045] The technical solution of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0046] This invention provides a method for the selective quantitative reduction of deuterated quinoline by a nickel catalyst. The method involves mixing materials including a quinoline heterocyclic compound, a nickel catalyst, a ligand, a borodeuteride / borohydride, and a deuterium / hydrogen source in an organic solvent, and reacting under light irradiation to obtain the deuterated quinoline heterocyclic compound. One of the reaction equations is shown below:

[0047] (1) ;

[0048] (2) ;

[0049] (3) ;

[0050] (4) ;

[0051] In the formula, R and R' are each independently selected from at least one of hydrogen, halogen, cyano, hydroxyl, trifluoromethyl, alkyl, alkoxy, aryloxy, acyloxy, ester, acyl, thiophene, oxazolyl, substituted or unsubstituted phenyl, amide, and substituted or unsubstituted benzophenyl. The substituents of the phenyl or benzophenyl are each independently selected from at least one of halogen, cyano, hydroxyl, trifluoromethyl, alkyl, alkoxy, aryloxy, acyloxy, ester, acyl, thiophene, oxazolyl, and amide. The halogen includes fluorine, chlorine, bromine, or iodine.

[0052] In some examples, the molar ratio of the quinoline heterocyclic compound, nickel catalyst, ligand, borodeuteride / borohydride, and deuterium source / hydrogen source is 1:(0.05~1):(0.05~1):(0.8~3):(0.5~3).

[0053] In some examples, the nickel catalyst is selected from at least one of [1,1′-bis(diphenylphosphine)ferrocene]nickel dichloride (Ni(dppf)Cl2), nickel iodide (NiI2), nickel chloride (NiCl2), nickel bromide (NiBr2), nickel carbonate (NiCO3), bis-(1,5-cyclooctadiene)nickel (Ni(cod)2), and nickel trifluoromethanesulfonate (Ni(OTf)2); the borodeuteride is selected from at least one of sodium borodeuteride (NaBD4), lithium borodeuteride (LiBD4), sodium cyanoborodeuteride (NaBD3CN), and sodium triethylborodeuteride (NaBDEt3); the borohydride is selected from at least one of sodium borohydride (NaBH4), lithium borohydride (LiBH4), sodium cyanoborodeuteride (NaBH3CN), and sodium triethylborohydride (NaBHEt3); and the ligand is selected from at least one of the following structures:

[0054] .

[0055] In some examples, the deuterium source is selected from deuterated hydrochloric acid (DCl), deuterated ethanol (EtOD), and deuterated tert-butanol (D&D). t At least one of BuOD, deuterated phosphoric acid (D3PO4), and deuterated boric acid (B(OD)3); the hydrogen source is 2,2,3,3,4,4,5,5-octafluoropentanol; the organic solvent is selected from acetonitrile and / or tetrahydrofuran.

[0056] In some examples, the wavelength of the illumination is 365~450 nm.

[0057] In some examples, the reaction temperature is 10–75 °C.

[0058] In some examples, the material also includes potassium persulfate (K2S2O8), in molar amounts 1 to 3 times that of quinoline heterocyclic compounds.

[0059] Example 1: Preparation of 1,2,3,4-tetrahydroquinoline-2,3,4-d3

[0060]

[0061] Under an argon atmosphere, Ni(dppf)Cl2 (0.020 mmol), 4,4'-dtbbpy (5.4 mg, 0.020 mmol), NaBD4 (8.4 mg, 0.20 mmol), and 0.50 mL of acetonitrile were added to a reaction flask, followed by quinoline (12.9 mg, 0.10 mmol) and DCl 20 wt.% in D2O (16.0 μL, 0.10 mmol). The reaction mixture was placed under 390 nm LED irradiation and stirred at 20 °C for 12 hours. The mixture was then purified by silica gel rapid column chromatography, eluting with a hexane / ethyl acetate mixture to give a yellow liquid 1,2,3,4-tetrahydroquinoline-2,3,4-d3 (12.4 mg, 91% yield). The R of the product was measured on a silica gel thin-layer plate using n-hexane-ethyl acetate as the developing solvent (n-hexane to ethyl acetate volume ratio of 10:1). f = 0.3.

[0062] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 7.15 - 6.92(m, 2H), 6.64 (t, J = 7.3, 1H), 6.51 (d, J = 7.9 Hz, 1H), 3.31 - 3.29 (m, 2H), 2.80 - 2.76 (m, 1H), 1.97 - 1.92 (m, 1H) ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3, 23℃, δ ): 144.86, 129.64, 126.85, 121.55, 117.09, 114.33, 41.65 (t, J = 20.8 Hz), 26.58 (t, J = 19.6 Hz), 21.71 (t, J = 19.6 Hz) ppm. 2 H{ 1 H} NMR (61 MHz, CH2Cl2, 23 ℃, δ): 3.27, 2.73, 1.88 ppm. HRMS-ESI (m / z) calc'd for C9H9D3N [M+H] + 137.1152; found, 137.1150.

[0063] Example 2: Preparation of 6-fluoro-1,2,3,4-tetrahydroquinoline-2,3,4-d3

[0064]

[0065] Following the method of Example 1, 6-fluoroquinoline (14.7 mg, 0.10 mmol) was reacted as a starting material to obtain a yellow liquid 6-fluoro-1,2,3,4-tetrahydroquinoline-2,3,4-d3 (15.1 mg, 98% yield). The product's R was measured on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 10:1). f = 0.3.

[0066] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 6.84 - 6.59(m, 2H), 6.44 (dd, J = 9.4, 4.9 Hz, 1H), 3.28 - 3.26 (m, 1H), 2.75 - 2.73 (m,1H), 1.95 - 1.92 (m, 1H) ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3, 23 ℃, δ ): 155.68 (d, J = 233.3 Hz), 140.89, 122.98, 115.77 (d, J = 21.5 Hz), 115.17 (d, J = 7.6 Hz), 113.35 (d, J = 22.4 Hz), 41.77 (t, J = 20.6 Hz), 26.64 (t, J = 20.0 Hz), 21.52(t, J = 19.6 Hz) ppm. 19 F NMR (376 MHz, CDCl3, 23 ℃, δ): - 128.18 ppm.2 H{ 1 H} NMR (61 MHz, CH2Cl2, 23 ℃, δ ): 3.24, 2.70, 1.88 ppm. HRMS-ESI (m / z) calc'd forC9H8D3FN [M+H] + 155.1058; found, 155.1054.

[0067] Example 3: Preparation of 8-fluoro-1,2,3,4-tetrahydroquinoline-2,3,4-d3

[0068]

[0069] Following the method of Example 1, 8-fluoroquinoline (14.7 mg, 0.10 mmol) was reacted as a starting material to obtain a yellow liquid 8-fluoro-1,2,3,4-tetrahydroquinoline-2,3,4-d3 (11.3 mg, yield 73%). The product's R was measured on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 10:1). f = 0.3.

[0070] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 6.84 - 6.59(m, 2H), 6.44 (dd, J = 9.4, 4.9 Hz, 1H), 3.28 - 3.26 (m, 1H), 2.75 - 2.73 (m,1H), 1.95 - 1.92 (m, 1H) ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3, 23 ℃, δ ): 155.68 (d, J = 233.3 Hz), 140.89, 122.98, 115.77 (d, J = 21.5 Hz), 115.17 (d, J = 7.6 Hz), 113.35 (d, J = 22.4 Hz), 41.77 (t, J = 20.6 Hz), 26.64 (t, J = 20.0 Hz), 21.52(t, J= 19.6 Hz) ppm. 19 F NMR (376 MHz, CDCl3, 23 ℃, δ): - 128.18 ppm. 2 H{ 1 H} NMR (61 MHz, CH2Cl2, 23 ℃, δ ): 3.24, 2.70, 1.88 ppm. HRMS-ESI (m / z) calc'd forC9H8D3FN [M+H] + 155.1058; found, 155.1054.

[0071] Example 4: Preparation of 6-chloro-1,2,3,4-tetrahydroquinoline-2,3,4-d3

[0072]

[0073] Following the method of Example 1, 6-chloroquinoline (16.3 mg, 0.10 mmol) was reacted as a starting material to obtain a yellow liquid 6-chloro-1,2,3,4-tetrahydroquinoline-2,3,4-d3 (16.0 mg, 94% yield). The product's R was measured on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 10:1). f = 0.3.

[0074] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 6.94 - 6.91(m, 2H), 6.42 (d, J = 8.0 Hz, 1H), 3.29 – 3.27 (m, 1H), 2.73 – 2.72 (m, 1H), 1.92 – 1.90 (m, 1H) ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3, 23 ℃, δ ): 143.29, 129.18,126.65, 123.04, 121.44, 115.30, 21.54 (t, J = 21.0 Hz), 26.48 (t, J = 19.6 Hz), 21.28 (t, J = 19.7 Hz) ppm. 2 H{ 1H} NMR (61 MHz, CH2Cl2, 23 ℃, δ ): 3.26, 2.71,1.87 ppm. HRMS-ESI (m / z) calc'd for C9H8D3ClN [M+H] + 171.0762; found, 171.0760.

[0075] Example 5: Preparation of tert-butyl-(tert-butoxycarbonyl)-(1,2,3,4-tetrahydroquinoline-6-yl-2,3,4-d3)carbamate

[0076]

[0077] Following the method of Example 1, tert-butyl(tert-butoxycarbonyl)(quinoline-6-yl)carbamate (34.4 mg, 0.10 mmol) was used as a starting material to obtain a colorless solid tert-butyl-(tert-butoxycarbonyl)-(1,2,3,4-tetrahydroquinoline-6-yl-2,3,4-d3)carbamate (26.3 mg, yield 75%). The product's R was measured on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 10:1). f = 0.3.

[0078] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 6.75 - 6.72(m, 2H), 6.44 (d, J = 8.8 Hz, 1H), 3.29 - 3.27 (m, 1H), 2.73 - 2.72 (m, 1H), 1.92 - 1.89 (m, 1H), 1.47 (s, 18H) ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3, 23 ℃, δ ):153.06, 143.87, 128.80, 128.78, 126.29, 121.57, 114.29, 82.35, 41.60 (t, J =20.9 Hz), 28.12, 26.45 (t, J = 19.6 Hz), 21.19 (t, J = 19.7 Hz) ppm. 2 H{ 1H} NMR (61 MHz, CH2Cl2, 23 ℃, δ ): 3.32, 2.80, 1.92 ppm. HRMS-ESI (m / z) calc'd forC 19 H 26 D3NO4[M+H] + 352.2310; found, 352.2305.

[0079] Example 6: Preparation of 5-methyl-1,2,3,4-tetrahydroquinoline-2,3,4-d3

[0080]

[0081] Following the method of Example 1, 5-methylquinoline (14.3 mg, 0.10 mmol) was reacted as a starting material to obtain a yellow liquid 5-methyl-1,2,3,4-tetrahydroquinoline-2,3,4-d3 (13.4 mg, yield 89%). The product's R was measured on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 10:1). f = 0.3.

[0082] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 6.91 (t, J =7.7 Hz, 1H), 6.54 (d, J = 7.4 Hz, 1H), 6.39 (d, J = 8.0 Hz, 1H), 3.26 - 3.24 (m,1H), 2.64 - 2.62(m, 1H), 2.20 (s, 3H), 1.99 - 1.98 (m, 1H) ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3, 23 ℃, δ ): 145.11, 137.37, 126.31, 120.29, 119.03, 112.56,41.26 (t, J = 20.9 Hz), 23.7 (t, J = 19.5 Hz), 22.1 ( J = 19.4 Hz), 19.5 ppm. 2 H{ 1H} NMR (61 MHz, CH2Cl2, 23 ℃, δ ): 3.22, 2.61, 1.93 ppm. HRMS-ESI (m / z) calc'd for C 10 H 11 D3N [M+H] + 151.1309; found, 151.1306.

[0083] Example 7: Preparation of 6-methyl-1,2,3,4-tetrahydroquinoline-2,3,4-d3

[0084]

[0085] Following the method of Example 1, 6-methylquinoline (14.3 mg, 0.10 mmol) was reacted as a starting material to obtain a yellow liquid 6-methyl-1,2,3,4-tetrahydroquinoline-2,3,4-d3 (12.9 mg, yield 86%). The product's R was measured on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 10:1). f = 0.3.

[0086] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 6.82 - 6.81(m, 2H), 6.46 (d, J = 8.6 Hz, 1H), 3.28 -3.26 (m, 1H), 2.75 - 2.74 (m, 1H), 2.23 (s, 3H), 1.94 - 1.93 (m, 1H) ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3, 23 ℃, δ ):142.30, 130.22, 127.39, 126.60, 121.84, 114.74, 41.86 (t, J = 20.6 Hz), 26.50(t, J = 19.2 Hz), 21.94 (t, J = 19.6 Hz), 20.54 ppm. 2 H{ 1 H} NMR (61 MHz, CH2Cl2, 23℃, δ): 3.24, 2.71, 1.88 ppm. HRMS-ESI (m / z) calc'd for C 10 H 11 D3N [M+H] + 151.1309; found, 151.1304.

[0087] Example 8: Preparation of 7-methyl-1,2,3,4-tetrahydroquinoline-2,3,4-d3

[0088]

[0089] Following the method of Example 1, 7-methylquinoline (14.3 mg, 0.10 mmol) was reacted as a starting material to obtain a yellow liquid 7-methyl-1,2,3,4-tetrahydroquinoline-2,3,4-d3 (14.7 mg, 98% yield). The product's R was measured on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 10:1). f = 0.3.

[0090] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 6.88 (d, J =7.2 Hz, 1H), 6.47 (d, J = 7.6 Hz, 1H), 6.35 (s, 1H), 3.29 - 3.28 (m, 2H), 2.74- 2.72 (m, 1H), 2.25 (s, 3H), 1.95 - 1.93 (m, 1H) ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3, 23 ℃, δ ): 144.61, 136.50, 129.52, 118.71, 118.14, 114.97, 41.69 (t, J =21.0 Hz), 26.19 (t, J = 19.7 Hz), 21.92 (t, J = 19.6 Hz), 21.24 ppm. 2 H{ 1 H} NMR (61 MHz, CH2Cl2, 23 ℃, δ): 3.25, 2.67, 1.87 ppm. HRMS-ESI (m / z) calc'd forC 10 H 11 D3N [M+H] + 151.1309; found, 151.1304.

[0091] Example 9: Preparation of 8-methyl-1,2,3,4-tetrahydroquinoline-2,3,4-d3

[0092]

[0093] Following the method of Example 1, 8-methylquinoline (14.3 mg, 0.10 mmol) was reacted as a starting material to obtain a yellow liquid 8-methyl-1,2,3,4-tetrahydroquinoline-2,3,4-d3 (14.3 mg, 95% yield). The product's R was measured on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 10:1). f = 0.3.

[0094] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 6.92 - 6.89(m, 2H), 6.62 (t, J = 7.2 Hz, 1H), 3.39 -3.37 (m, 1H), 2.80 - 2.79(m, 1H), 2.12(s, 1H), 1.98 - 1.95 (m, 1H) ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3, 23 ℃, δ ):142.68, 127.99, 127.51, 121.45, 121.07, 116.66, 42.03 (t, J = 20.7 Hz), 26.89(t, J = 19.6 Hz), 21.67 (t, J = 19.7 Hz), 17.30 ppm. 2 H{ 1 H} NMR (61 MHz, CH2Cl2, 23 ℃, δ ): 3.36, 2.67, 1.89 ppm. HRMS-ESI (m / z) calc'd for C 10H 11 D3N [M+H] + 151.1309; found, 151.1304.

[0095] Example 10: Preparation of 6-phenyl-1,2,3,4-tetrahydroquinoline-2,3,4-d3

[0096]

[0097] Following the method of Example 1, 6-phenylquinoline (20.5 mg, 0.10 mmol) was reacted as a starting material to obtain a yellow liquid 6-phenyl-1,2,3,4-tetrahydroquinoline-2,3,4-d3 (18.2 mg, yield 86%). The product's R was measured on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 10:1). f = 0.2.

[0098] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 7.63 - 7.52(m, 2H), 7.43 - 7.40 (m, 2H), 7.36 - 7.24 (m, 3H), 6.58 (d, J = 7.9 Hz, 1H), 3.35 - 3.33 (m, 1H), 2.85 - 2.83 (m, 1H), 2.01 - 1.96 (m, 1H) ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3, 23 ℃, δ ): 144.34, 141.61, 130.07, 128.70, 128.31, 126.39,126.02, 125.64, 121.68, 114.58, 41.69 (t, J = 20.9 Hz), 26.74 (t, J = 19.6 Hz), 21.70 (t, J = 19.4 Hz) ppm. 2 H{ 1 H} NMR (61 MHz, CH2Cl2, 23 ℃, δ ): 3.32, 2.81,1.94 ppm. HRMS-ESI (m / z) calc'd for C 15 H13 D3N [M+H] + 213.1466; found, 213.1460.

[0099] Example 11: Preparation of 6-(3,5-difluorophenyl)-1,2,3,4-tetrahydroquinoline-2,3,4-d3

[0100]

[0101] Following the method of Example 1, 6-(3,5-difluorophenyl)quinoline (24.1 mg, 0.10 mmol) was reacted as a starting material to obtain a colorless solid 6-(3,5-difluorophenyl)-1,2,3,4-tetrahydroquinoline-2,3,4-d3 (23.1 mg, 93% yield). The product's R was measured on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 10:1). f = 0.2.

[0102] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 7.25 - 7.17(m, 2H), 7.13 - 6.99 (m, 2H), 6.69 (t, J = 8.9, 2.3 Hz, 1H), 6.60 - 6.52 (m,1H), 3.35 - 3.34 (m, 1H), 2.82 - 2.81 (m, 1H), 1.98 - 1.95 (m, 1H) ppm. 13 C{ 1 H}NMR (100 MHz, CDCl3, 23 ℃, δ ): 163.52 (d, J = 245.0 Hz), 163.18 (d, J = 245.0Hz), 145.31, 144.95 (t, J = 9.7 Hz), 128.10, 127.25 (t, J = 2.6 Hz), 125.51,121.60, 114.37, 108.66 (d, J = 11.8 Hz), 108.66 (d, J = 25.3 Hz), 100.96 (t, J =25.6 Hz), 41.56 (t,J = 20.8 Hz), 26.72 (t, J = 19.7 Hz), 21.46 (t, J = 19.9 Hz)ppm. 19 F NMR (376 MHz, CDCl3, 23 ℃, δ): - 110.61 (m) ppm. 2 H{ 1 H} NMR (61 MHz, CH2Cl2, 23 ℃, δ ): 3.32, 2.78, 1.92 ppm. HRMS-ESI (m / z) calc'd for C 15 H 11 D3F2N [M+H] + 249.1277; found, 249.1271.

[0103] Example 12: Preparation of 6-(4-trifluoromethylphenyl)-1,2,3,4-tetrahydroquinoline-2,3,4-d3

[0104]

[0105] Following the method of Example 1, 6-(4-trifluoromethylphenyl)quinoline (24.1 mg, 0.10 mmol) was reacted as a starting material to obtain a colorless solid 6-(4-trifluoromethylphenyl)-1,2,3,4-tetrahydroquinoline-2,3,4-d3 (24.6 mg, yield 88%). The product's R was measured on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 10:1). f = 0.3.

[0106] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 7.64 - 7.63(m, 4H), 7.29 - 7.26 (m, 2H), 6.59 - 6.58 (m, 1H), 3.38 - 3.45 (m, 1H), 2.84- 2.82 (m, 1H), 1.99 - 1.98 (m, 1H) ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3, 23 ℃, δ ): 145.14, 145.04, 128.40, 128.12, 127.85(q,J = 32.1 Hz), 126.28, 125.81,125.65 (q, J = 3.9 Hz), 124.68 (q, J = 269.9 Hz), 121.72, 114.51, 41.59 (t, J = 20.9 Hz), 26.75(t, J = 19.4 Hz), 21.51(t, J = 19.6 Hz) ppm. 19 F NMR (376MHz, CDCl3, 23 ℃, δ): -62.13 ppm. 2 H{ 1 H} NMR (61 MHz, CH2Cl2, 23 ℃, δ ): 3.33,2.81, 1.93 ppm. HRMS-ESI (m / z) calc'd for C 16 H 12 D3F3N [M+H] + 281.1339; found, 281.1332.

[0107] Example 13: Preparation of 6-(4-trifluoromethoxyphenyl)-1,2,3,4-tetrahydroquinoline-2,3,4-d3

[0108]

[0109] Following the method of Example 1, 6-(4-trifluoromethoxyphenyl)quinoline (28.9 mg, 0.10 mmol) was reacted as a starting material to obtain a colorless solid 6-(4-trifluoromethoxyphenyl)-1,2,3,4-tetrahydroquinoline-2,3,4-d3 (26.9 mg, 91% yield). The product's Rf was measured to be 0.3 on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 10:1).

[0110] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 7.43 (d, J =8.7 Hz, 2H), 7.15 - 7.07 (m, 4H), 6.46 (d, J= 8.0 Hz, 1H), 3.39 - 3.15 (m,1H), 2.72 - 2.71 (m, 1H), 1.89 - 1.85 (m, 1H) ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3,23 ℃, δ ): 147.71 (q, J = 1.9 Hz), 144.66, 140.45, 128.50, 128.28, 127.47,125.62,121.72, 121.27,120.71 (q, J = 255.3 Hz), 114.54, 41.63 (t, J = 20.9 Hz), 26.74 (t, J = 19.4 Hz), 21.60 (t, J = 19.7 Hz) ppm. 19 F NMR (376 MHz, CDCl3, 23 ℃, δ): - 57.84 ppm. 2 H{ 1 H} NMR (61 MHz, CH2Cl2, 23 ℃, δ ): 3.32, 2.79, 1.93 ppm.HRMS-ESI (m / z) calc'd for C 16 H 12 D3F3NO [M+H] + 297.1288; found, 297.1281.

[0111] Example 14: Preparation of 6-(4-methoxyphenyl)-1,2,3,4-tetrahydroquinoline-2,3,4-d3

[0112]

[0113] Following the method of Example 1, 6-(4-methoxyphenyl)quinoline (23.5 mg, 0.10 mmol) was reacted as a starting material to obtain a colorless solid 6-(4-methoxyphenyl)-1,2,3,4-tetrahydroquinoline-2,3,4-d3 (23.8 mg, 98% yield). The product's R was measured on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 10:1). f = 0.3.

[0114] The structural characterization data of the product are as follows:1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 7.43 (d, J =8.7 Hz, 2H), 7.15 - 7.07 (m, 4H), 6.46 (d, J = 8.0 Hz, 1H), 3.39 - 3.15 (m,1H), 2.72 - 2.71 (m, 1H), 1.89 - 1.85 (m, 1H) ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3,23 ℃, δ ): 147.71 (q, J = 1.9 Hz), 144.66, 140.45, 128.50, 128.28, 127.47,125.62,121.72, 121.27,120.71 (q, J = 255.3 Hz), 114.54, 41.63 (t, J = 20.9 Hz), 26.74 (t, J = 19.4 Hz), 21.60 (t, J = 19.7 Hz) ppm. 19 F NMR (376 MHz, CDCl3, 23 ℃, δ): - 57.84 ppm. 2 H{ 1 H} NMR (61 MHz, CH2Cl2, 23 ℃, δ ): 3.32, 2.79, 1.93 ppm.HRMS-ESI (m / z) calc'd for C 16 H 12 D3F3NO [M+H] + 297.1288; found, 297.1281.

[0115] Example 15: Preparation of 6-(furan-3-yl)-1,2,3,4-tetrahydroquinoline-2,3,4-d3

[0116]

[0117] Following the method of Example 1, 6-(furan-3-yl)quinoline (19.5 mg, 0.10 mmol) was reacted as a starting material to obtain a colorless solid 6-(furan-3-yl)-1,2,3,4-tetrahydroquinoline-2,3,4-d3 (18.2 mg, 90% yield). The product's R was measured on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 10:1). f = 0.3.

[0118] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 7.62 (d, J =1.4 Hz, 1H), 7.45 (d, J = 1.7 Hz, 1H), 7.14 - 7.12 (m, 2H), 6.68 - 6.62 (m,1H), 6.52 (d, J = 7.9 Hz, 1H), 3.32 - 3.30 (m, 1H), 2.80 - 2.78 (m, 1H), 1.97 -1.94 (m, 1H) ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3, 23 ℃, δ ): 143.98, 143.32,137.07, 127.23, 126.80, 124.65, 121.76, 121.35, 114.60, 108.97, 41.69 (t, J =20.7 Hz), 26.63 (t, J = 19.5 Hz), 21.69 (t, J = 19.7 Hz) ppm. 2 H{ 1 H} NMR (61 MHz, CH2Cl2, 23 ℃, δ ): 3.29, 2.75, 1.91 ppm. HRMS-ESI (m / z) calc'd for C 13 H 11 D3NO [M+H] + 203.1258; found, 203.1254.

[0119] Example 16: Preparation of 1,2,3,4-tetrahydro-1,5-naphthidine-2,3,4-d3

[0120]

[0121] Following the method of Example 1, a colorless solid (1,2,3,4-tetrahydro-1,5-naphthidine-2,3,4-d39.6 mg, yield 70%) was obtained from 1,5-naphthidine (13.0 mg, 0.10 mmol) as the starting material. The product's R0 was measured on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 10:1). f = 0.3.

[0122] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 8.06 (d, J =5.6 Hz, 1H), 7.02 - 6.89 (m, 2H), 4.19 (s, 1H), 3.29 (s, 1H), 3.23 - 3.19 (m,1H), 2.04 - 2.00 (m, 1H) ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3, 23 ℃, δ ): 143.09,141.48, 137.53, 122.60, 122.49, 40.31 (t, J = 21.0 Hz), 26.51 (t, J = 20.4 Hz), 20.33 (t, J = 19.9 Hz) ppm. 2 H{ 1 H} NMR (61 MHz, CH2Cl2, 23 ℃, δ ): 3.27, 3.18,1.98 ppm. HRMS-ESI (m / z) calc'd for C8H8D3N2[M+H] + 138.1105; found, 138.1102.

[0123] Example 17: Preparation of 1,2,3,4-tetrahydroquinoline-2,4-d2

[0124]

[0125] Under an argon atmosphere, NiI₂ (6.3 mg, 0.020 mmol), sarcosine (8.9 mg, 0.10 mmol), NaBD₄ (8.4 mg, 0.20 mmol), and 0.50 mL of acetonitrile were added to a reaction flask, followed by the addition of quinoline (12.9 mg, 0.10 mmol) and FOH (46.4 mg, 0.20 mmol) to obtain a reaction mixture. The reaction mixture was placed under 390 nm LED irradiation and stirred at 20 °C for 12 hours. Purification was then performed by rapid silica gel column chromatography, eluting with a hexane / ethyl acetate mixture to give a yellow liquid 1,2,3,4-tetrahydroquinoline-2,4-d₂ (12.1 mg, 89% yield). The product's R₂ was measured on a silica gel thin-layer plate using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 10:1). f = 0.3.

[0126] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 7.00 - 6.96(m, 2H), 6.62 (td, J = 7.4, 1.1 Hz, 1H), 6.49 (d, J = 7.9 Hz, 1H), 3.82 (s,1H), 3.34 - 3.29 (m, 1H), 2.80 - 2.77 (m, 1H), 1.95 (t, J = 6.1 Hz, 2H) ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3, 23 ℃, δ ): 144.89, 129.62, 126.83, 121.50,117.03, 114.29, 41.71 (t, J = 21.3 Hz), 26.67(t, J = 19.6 Hz), 22.06 ppm. 2 H{ 1 H} NMR (61 MHz, CH2Cl2, 23 ℃, δ ): 3.27, 2.71 ppm. HRMS-ESI (m / z) calc'd forC9H 10 D2N [M+H] + 136.1090; found, 136.1087.

[0127] Example 18: Preparation of 6-chloro-1,2,3,4-tetrahydroquinoline-2,4-d2

[0128]

[0129] Following the method of Example 17, 6-chloroquinoline (16.3 mg, 0.10 mmol) was reacted as a starting material to obtain a colorless solid, 6-chloro-1,2,3,4-tetrahydroquinoline-2,4-d2 (11.2 mg, yield 66%). The product's R was measured on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 10:1). f = 0.3.

[0130] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 6.92 (d, J =8.7 Hz, 2H), 6.41 (d, J = 8.3 Hz, 1H), 3.30 - 3.27 (m, 1H), 2.74 - 2.73 (m,1H), 1.92 (t, J = 6.3 Hz, 2H) ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3, 23 ℃, δ ): 143.35,129.17, 126.65, 123.00, 121.37, 115.26, 41.61 (t, J = 21.0 Hz), 26.60 (t, J =19.9 Hz), 21.65 ppm. 2 H{ 1 H} NMR (61 MHz, CH2Cl2, 23 ℃, δ ): 3.23, 2.66 ppm.HRMS-ESI (m / z) calc'd for C9H9D2ClN [M+H] + 170.0700; found, 170.0697.

[0131] Example 19: Preparation of 6-fluoro-1,2,3,4-tetrahydroquinoline-2,4-d2

[0132]

[0133] Following the method of Example 17, 6-fluoroquinoline (14.7 mg, 0.10 mmol) was reacted as a starting material to obtain a yellow liquid 6-fluoro-1,2,3,4-tetrahydroquinoline-2,4-d2 (12.4 mg, yield 81%). The product's R was measured on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 10:1). f = 0.3.

[0134] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 6.72 - 6.68(m, 2H), 6.45 - 6.41 (m, 1H), 3.30 - 3.25 (m, 1H), 2.78 - 2.73(m, 1H), 1.93(t, J = 6.2 Hz, 2H) ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3, 23 ℃, δ ): 155.65 (d, J =234.7 Hz), 140.93, 122.96 (d, J = 6.5 Hz), 115.75 (d, J = 21.5 Hz), 115.13 (d, J =7.6 Hz), 113.34 (d, J = 22.4 Hz), 41.84 (t, J = 20.5 Hz), 26.74 (t, J = 19.5 Hz), 21.88 ppm. 19 F NMR (376 MHz, CDCl3, 23 ℃, δ): - 128.22 ppm. 2 H{ 1 H} NMR (61 MHz, CH2Cl2, 23 ℃, δ ): 3.25, 2.72 ppm. HRMS-ESI (m / z) calc'd for C9H9D2FN [M+H] + 154.0996; found, 154.0992.

[0135] Example 20: Preparation of tert-butyl-(tert-butoxycarbonyl)-(1,2,3,4-tetrahydroquinoline-6-yl-2,3,4-d2)carbamate

[0136]

[0137] Following the method of Example 17, tert-butyl-(tert-butoxycarbonyl)-(quinoline-6-yl)carbamate (34.4 mg, 0.10 mmol) was used as a starting material to obtain a colorless solid tert-butyl-(tert-butoxycarbonyl)-(1,2,3,4-tetrahydroquinoline-6-yl-2,3,4-d2)carbamate (18.9 mg, yield 54%). The product's R was measured on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 10:1). f = 0.2.

[0138] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 6.73 (d, J =3.7 Hz, 2H), 6.42 (d, J = 8.8 Hz, 1H), 3.87 (s, 1H), 3.29 - 3.26 (m, 1H), 2.77- 2.71 (m, 1H), 1.91 (t, J = 6.2 Hz, 1H), 1.47 (s, 18H) ppm. 13 C{ 1 H} NMR (100MHz, CDCl3, 23 ℃, δ ): 153.06, 144.07, 128.75, 128.58, 126.25, 121.39, 114.12,82.31, 41.64 (t, J = 21.0 Hz), 28.11, 26.76 (t J = 19.1 Hz), 21.76 ppm. 2 H{ 1 H}NMR (61 MHz, CH2Cl2, 23 ℃, δ ): 3.28, 2.72 ppm. HRMS-ESI (m / z) calc'd forC 19 H 27 D2N2O4[M+H] + 351.2247; found, 351.2238.

[0139] Example 21: Preparation of 5-methyl-1,2,3,4-tetrahydroquinoline-2,4-d2

[0140]

[0141] Following the method of Example 17, 5-methylquinoline (14.3 mg, 0.10 mmol) was reacted as a starting material to obtain a yellow liquid 5-methyl-1,2,3,4-tetrahydroquinoline-2,4-d2 (11.2 mg, 75% yield). The product's R was measured on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 10:1). f = 0.3.

[0142] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 6.91 (t, J =7.7 Hz, 1H), 6.54 (d, J = 7.4 Hz, 1H), 6.39 (d, J = 8.0 Hz, 1H), 3.30 - 3.25 (m,1H), 2.68 - 2.62 (m, 1H), 2.20 (s, 3H), 2.00 (t, J = 6.2 Hz, 2H) ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3, 23 ℃, δ ): 145.11, 137.37, 126.32, 120.29, 119.03, 112.57,41.34 (t, J = 21.0 Hz), 23.80 (t, J = 19.3 Hz), 22.46, 19.51 ppm. 2 H{ 1 H} NMR (61MHz, CH2Cl2, 23 ℃, δ ): 3.22, 2.59 ppm. HRMS-ESI (m / z) calc'd for C 10 H 12 D2N [M+H] + 150.1246; found, 150.1242.

[0143] Example 22: Preparation of 7-methyl-1,2,3,4-tetrahydroquinoline-2,4-d2

[0144]

[0145] Following the method of Example 17, 7-methylquinoline (14.3 mg, 0.10 mmol) was reacted as a starting material to obtain a yellow liquid 7-methyl-1,2,3,4-tetrahydroquinoline-2,4-d2 (12.7 mg, yield 85%). The product's R was measured on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 10:1). f = 0.3.

[0146] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 6.87 (d, J =7.5 Hz, 1H), 6.46 (d, J = 7.5 Hz, 1H), 6.34 (s, 1H), 3.30 - 3.27 (m, 1H), 2.77- 2.72 (m, 1H), 2.25 (s, 3H), 1.94 (t, J = 6.1 Hz, 2H) ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3, 23 ℃, δ ): 144.75, 136.50, 129.51, 118.63, 118.03, 114.89, 41.77 (t, J =20.7 Hz), 26.33 (t, J = 19.3 Hz), 22.31, 21.25 ppm. 2 H{ 1 H} NMR (61 MHz, CH2Cl2, 23 ℃, δ ): 3.24, 2.66 ppm. HRMS-ESI (m / z) calc'd for C 10 H 12 D2N [M+H] + 150.1246;found, 150.1242.

[0147] Example 23: Preparation of 6-phenyl-1,2,3,4-tetrahydroquinoline-2,4-d2

[0148]

[0149] Following the method of Example 17, 6-phenylquinoline (14.3 mg, 0.10 mmol) was reacted as a starting material to obtain a yellow liquid 6-phenyl-1,2,3,4-tetrahydroquinoline-2,4-d2 (14.3 mg, yield 68%). The product's R was measured on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 10:1). f = 0.3.

[0150] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 7.60 - 7.52(m, 2H), 7.41 (t, J = 7.8 Hz, 2H), 7.32 - 7.23 (m, 3H), 6.58 (d, J = 8.0 Hz, 1H),3.38 - 3.33 (m, 1H), 2.88 - 2.83 (m, 1H), 2.00 (t, J = 6.1 Hz, 2H) ppm. 13 C{ 1 H}NMR (100 MHz, CDCl3, 23 ℃, δ ): 144.27, 141.59, 130.09, 128.70, 128.30,126.38, 126.02, 125.64, 121.71, 114.62, 41.76 (t, J = 20.9 Hz), 26.83 (t, J =19.4 Hz), 22.04 ppm. 2 H{ 1 H} NMR (61 MHz, CH2Cl2, 23 ℃, δ ): 3.32, 2.81 ppm.HRMS-ESI (m / z) calc'd for C 15 H 14 D2N [M+H] + 212.1403; found, 212.1397.

[0151] Example 24: Preparation of 6-(4-methoxyphenyl)-1,2,3,4-tetrahydroquinoline-2,4-d2

[0152]

[0153] Following the method of Example 17, 6-(4-methoxyphenyl)quinoline (23.5 mg, 0.10 mmol) was reacted as a starting material to obtain a colorless solid 6-(4-methoxyphenyl)-1,2,3,4-tetrahydroquinoline-2,4-d2 (17.4 mg, yield 72%). The product's R was measured on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 10:1). f = 0.3.

[0154] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 7.51 - 7. 48(m, 2H), 7.23 (d, J = 8.9 Hz, 2H), 6.99 -6.96 (m, 2H), 6.58 (d, J = 8.1 Hz, 1H),3.87 (s, 3H), 3.68 (s, 1H), 3.38 - 3.33 (m, 1H), 2.86 (m, 1H), 2.00 (t, J = 6.3Hz, 1H) ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3, 23 ℃, δ ): 158.27, 143.82, 134.35,129.86, 127.90, 127.36, 125.25, 121.71, 114.65, 114.14, 55.42, 41.77(t, J =20.9 Hz), 26.83 (t, J = 19.5 Hz), 22.10 ppm. 2 H{ 1 H} NMR (61 MHz, CH2Cl2, 23 ℃, δ ): 3.30, 2.79 ppm. HRMS-ESI (m / z) calc'd for C 16 H 16 D2NO [M+H] + 242.1508; found, 242.1501.

[0155] Example 25: Preparation of 6-(furan-3-yl)-1,2,3,4-tetrahydroquinoline-2,4-d2

[0156]

[0157] Following the method of Example 17, 6-(furan-3-yl)quinoline (19.5 mg, 0.10 mmol) was reacted as a starting material to obtain a yellow liquid 6-(furan-3-yl)-1,2,3,4-tetrahydroquinoline-2,4-d2 (17.3 mg, yield 86%). The product's Rf was measured to be 0.3 using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 10:1) on silica gel thin-layer chromatography.

[0158] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 7.71 - 7.59(m, 1H), 7.47 (d, J = 1.7 Hz, 1H), 7.14 (d, J = 7.7 Hz, 2H), 6.66 (s, 1H), 6.52(d, J = 7.9 Hz, 1H), 3.55 (s, 1H), 3.36 - 3.31 (m, 1H), 2.84 - 2.79 (m, 1H), 1.98 (t, J = 6.1 Hz, 2H) ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3, 23 ℃, δ ): 144.05,143.29, 137.02, 127.17, 126.78, 124.61, 121.66, 121.21, 114.51, 108.94, 41.72(t, J = 21.0 Hz), 26.72 (t, J = 19.6 Hz), 22.03 ppm. 2 H{ 1 H} NMR (61 MHz, CH2Cl2, 23 ℃, δ ): 3.30, 2.77 ppm. HRMS-ESI (m / z) calc'd for C 13 H 12 D2NO [M+H] +202.1195;found, 202.1190.

[0159] Example 26: Preparation of 1,2,3,4-tetrahydroquinoxaline-2,3-d2

[0160]

[0161] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 7.00 - 6.96(m, 2H), 6.64 - 6.60 (m, 1H), 6.49 (d, J = 7.9 Hz, 1H), 3.82 (s, 1H), 3.34 -3.29(m, 1H), 2.80 - 2.77 (m, 1H), 1.95 (t, J = 6.1 Hz, 1H) ppm. 13 C{ 1 H} NMR (100MHz, CDCl3, 23 ℃, δ ): 133.81, 118.88, 114.83, 41.70 - 40.74 (m) ppm. 2 H{ 1 H} NMR (61 MHz, CH2Cl2, 23 ℃, δ ): 3.36 ppm. HRMS-ESI (m / z) calc'd for C8H9D2N2[M+H] + 137.1042; found, 137.1040.

[0162] Example 27: Preparation of 5-fluoro-1,2,3,4-tetrahydroquinoxaline-2,3-d2

[0163]

[0164] Following the method of Example 17, 5-fluoroquinoxaline (13.0 mg, 0.10 mmol) was reacted as a starting material to obtain a colorless solid of 5-fluoro-1,2,3,4-tetrahydroquinoxaline-2,3-d2 (11.1 mg, yield 72%). The product's R was measured on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 3:1). f = 0.2.

[0165] The structural characterization data of the product are as follows: 1H NMR (400 MHz, CDCl3, 23 ℃, δ ): 6.53 - 6.42(m, 2H), 6.31 (d, J = 7.8 Hz, 1H), 3.60 (s, 2H), 3.43 (s, 2H) ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3, 23 ℃, δ ): 151.65 (d, J = 235.4 Hz), 135.18 (d, J = 6.6 Hz), 121.98 (d, J = 15.7 Hz), 117.51 ​​(d, J = 9.2 Hz), 110.06 (d, J = 2.3 Hz), 105.09(d, J = 18.9 Hz), 47.06 - 36.35 (m) ppm. 19 F NMR (376 MHz, CDCl3, 23 ℃, δ): -137.93 ppm. 2 H{ 1 H} NMR (61 MHz, CH2Cl2, 23 ℃, δ ): 3.39 ppm. HRMS-ESI (m / z)calc'd for C8H8D2FN2[M+H] + 155.0948; found, 155.0945.

[0166] Example 28: Preparation of 6-trifluoromethyl-1,2,3,4-tetrahydroquinoxaline-2,3-d2

[0167]

[0168] Following the method of Example 17, 6-trifluoromethylquinoxaline (13.0 mg, 0.10 mmol) was used as a starting material to obtain a colorless solid, 6-trifluoromethyl-1,2,3,4-tetrahydroquinoxaline-2,3-d2 (9.8 mg, yield 48%). The product's R was measured on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 3:1). f =0.2.

[0169] The structural characterization data of the product are as follows: 1H NMR (400 MHz, CDCl3, 23 ℃, δ ): 6.84 (dd, J =8.2, 2.0 Hz, 1H), 6.70 (s, 1H), 6.48 (d, J = 8.1 Hz, 1H), 3.90 (s, 2H), 3.64 -3.28 (m, 2H) ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3, 23 ℃, δ ): 136.65, 133.13, 125.03(q, J = 269.0 Hz), 120.10 (q, J = 32.2 Hz), 116.04 (q, J = 4.1 Hz), 113.26, 110.97 (q, J = 3.9 Hz), 41.90 – 39.11 (m) ppm. 19 F NMR (376 MHz, CDCl3, 23 ℃, δ): - 61.21 ppm. 2 H{ 1 H} NMR (61 MHz, CH2Cl2, 23 ℃, δ ): 3.39 ppm. HRMS-ESI (m / z)calc'd for C9H8D2F3N2[M+H] + 205.0916; found, 205.0913.

[0170] Example 29: Preparation of methyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylate-2,3-d2

[0171]

[0172] Following the method of Example 17, methyl quinoxaline-6-carboxylate (18.8 mg, 0.10 mmol) was used as a starting material to obtain a colorless solid, methyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylate-2,3-d2 (10.1 mg, yield 52%). The product's R was measured on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 3:1). f = 0.2.

[0173] The structural characterization data of the product are as follows: 1H NMR (400 MHz, CDCl3, 23 ℃, δ ): 7.34 (dd, J =8.2, 1.9 Hz, 1H), 7.19 (d, J = 1.9 Hz, 1H), 6.44 (d, J = 8.2 Hz, 1H), 3.85 (s,3H), 3.52 - 3.45 (m, 1H), 3.40 - 3.37 (m, 1H) ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3,23 ℃, δ ): 167.64, 138.55, 132.47, 121.86, 119.23, 115.55, 112.77, 51.65,40.94 (t, J = 21.0 Hz), 40.19 (t, J = 21.1 Hz) ppm. 2 H{ 1 H} NMR (61 MHz, CH2Cl2, 23 ℃, δ ): 3.31, 3.23 ppm. HRMS-ESI (m / z) calc'd for C 10 H 11 D2N2O2[M+H] + 195.1097; found, 195.1094.

[0174] Example 30: Preparation of 1,2,3,4-tetrahydroquinoxaloline-6-nitrile-2,3-d2

[0175]

[0176] Following the method of Example 17, 1,2,3,4-tetrahydroquinoxaloline-6-onitrile (15.5 mg, 0.10 mmol) was reacted as a starting material to obtain a colorless solid, 1,2,3,4-tetrahydroquinoxaloline-6-onitrile-2,3-d2 (9.3 mg, yield 58%). The product's R0 was measured on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 3:1). f = 0.2.

[0177] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 6.88 (d,J =8.0 Hz, 1H), 6.69 (s, 1H), 6.42 (d, J = 8.1 Hz, 1H), 4.21 (s, 1H), 3.87 (s,1H), 3.48 - 3.46 (m, 1H), 3.40 - 3.37 (m, 1H) ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3,23 ℃, δ ): 138.08, 133.14, 123.98, 120.92, 116.60, 113.19, 99.38, 40.59 (t, J =21.3 Hz), 39.82 (t, J = 21.3 Hz) ppm. 2 H{ 1 H} NMR (61 MHz, CH2Cl2, 23 ℃, δ ): 3.43,3,35 ppm. HRMS-ESI (m / z) calc'd for C9H8D2N3[M+H] + 162.0995; found, 162.0991.

[0178] Example 31: Preparation of 6-methyl-1,2,3,4-tetrahydroquinoxaline-2,3-d2

[0179]

[0180] Following the method of Example 17, 6-methylquinoxaline (14.4 mg, 0.10 mmol) was used as a starting material to obtain a colorless solid, 6-methyl-1,2,3,4-tetrahydroquinoxaline-2,3-d2 (12.3 mg, yield 82%). The product's R was measured on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 3:1). f = 0.2.

[0181] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 6.45 - 6.40(m, 2H), 6.35 (s, 1H), 3.40 (s, 2H), 2.19 (s, 3H) ppm. 13 C{ 1H} NMR (100 MHz, CDCl3, 23 ℃, δ ): 133.89, 131.27, 128.54, 119.26, 115.58, 115.14, 41.30 (t, J =20.6 Hz), 20.79 ppm. 2 H{ 1 H} NMR (61 MHz, CH2Cl2, 23 ℃, δ ): 3.34 ppm. HRMS-ESI(m / z) calc'd for C9H 11 D2N2[M+H] + 151.1199; found, 151.1196.

[0182] Example 32: Preparation of 6-phenyl-1,2,3,4-tetrahydroquinoxaline-2,3-d2

[0183]

[0184] Following the method of Example 17, 6-phenylquinoxaline (20.6 mg, 0.10 mmol) was used as a starting material to react and yield a colorless solid of 6-phenyl-1,2,3,4-tetrahydroquinoxaline-2,3-d2 (17.2 mg, yield 81%). The product's R was measured on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 3:1). f = 0.2.

[0185] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 7.54 (d, J =7.5 Hz, 2H), 7.40 (t, J = 7.7 Hz, 2H), 7.33 - 7.23 (m, 1H), 6.97 - 6.86 (m,1H), 6.78 (d, J = 2.0 Hz, 1H), 6.59 (d, J = 8.0 Hz, 1H), 3.45 (s, 4H) ppm. 13 C{ 1 H}NMR (100 MHz, CDCl3, 23 ℃, δ): 141.70, 133.88, 133.41, 131.94, 128.65,126.53, 126.18, 117.77, 114.92, 113.36, 41.22 - 40.82 (m) ppm. 2 H{ 1 H} NMR (61MHz, CH2Cl2, 23 ℃, δ ): 3.39 ppm. HRMS-ESI (m / z) calc'd for C 14 H 13 D2N2[M+H] + 213.1355; found, 213.1354.

[0186] Example 33: Preparation of 1,2,3,4-tetrahydrobenzoquinoxaline-2,3-d2

[0187]

[0188] Following the method of Example 17, benzoquinoxaline (18.0 mg, 0.10 mmol) was used as a starting material to react and yield a colorless solid, 1,2,3,4-tetrahydrobenzoquinoxaline-2,3-d2 (16.2 mg, yield 87%). The product's R0 was measured on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 3:1). f = 0.2.

[0189] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 7.49 - 7.46(m, 2H), 7.15 - 7.13 (m, 2H), 6.79 (s, 2H), 4.08 (s, 2H), 3.51 - 3.47 (s, 2H)ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3, 23 ℃, δ ): 135.38, 129.09, 125.20, 122.56,107.81, 40.85(t, J = 21.0 Hz) ppm. 2 H{ 1 H} NMR (61 MHz, CH2Cl2, 23 ℃, δ): 3.44ppm. HRMS-ESI (m / z) calc'd for C 12 H 11 D2N2[M+H] + 187.1199; found, 187.1195.

[0190] Example 34: Preparation of 9,10-dihydroacridine-9-deuterium

[0191]

[0192] Following the method of Example 17, acridine (17.9 mg, 0.10 mmol) was reacted as a starting material to obtain a colorless solid of 9,10-dihydroacrylidine-9-deuterium (16.2 mg, yield 89%). The product's R0 was measured on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 3:1). f = 0.2.

[0193] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 7.16 - 6.99(m, 4H), 6.86 - 6.82 (m, 2H), 6.64 (d, J = 7.9 Hz, 2H), 5.92 (s, 1H), 4.04 -4.01 (m, 1H) ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3, 23 ℃, δ ): 140.25, 128.73,127.12, 120.75, 120.10, 113.56, 31.14 (t, J = 19.8 Hz) ppm. 2 H{ 1 H} NMR (61 MHz, CH2Cl2, 23 ℃, δ ): 4.06 ppm. HRMS-ESI (m / z) calc'd for C 13 H 11 DN [M+H] + 183.1027;found, 183.1024.

[0194] Example 35: Preparation of 1,2,3,4-tetrahydroquinoline-3-d

[0195]

[0196] Under an argon atmosphere, Ni(dppf)Cl2 (13.6 mg, 0.020 mmol), L (4.5 mg, 0.020 mmol), NaBH4 (7.6 mg, 0.20 mmol), and 0.50 mL of acetonitrile were added to a reaction flask. Quinoline (12.9 mg, 0.10 mmol) and DCl 20 wt.% in D2O (16.0 μL, 0.10 mmol) were then added to obtain the reaction mixture. The reaction mixture was placed under 390 nm LED irradiation and stirred at 20 °C for 12 hours. Purification was then performed by silica gel rapid column chromatography, eluting with a hexane / ethyl acetate mixture to give a yellow liquid 1,2,3,4-tetrahydroquinoline-3-d (12.3 mg, 92% yield). The product's R... f = 0.3.

[0197] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 6.99 (t, J =8.0 Hz, 2H), 6.65 – 6.62 (m, 1H), 6.50 (d, J = 7.9 Hz, 1H), 3.32 (t, J = 5.5 Hz, 3H), 2.79 (t, J = 6.4 Hz, 2H), 2.12 - 1.86 (m, 1H) ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3, 23 ℃, δ ): 144.89, 129.65, 126.84, 121.59, 117.09, 114.32, 42.04,26.99, 21.95 (t, J = 19.7 Hz) ppm. 2 H{ 1 H} NMR (61 MHz, CH2Cl2, 23 ℃, δ ): 1.89ppm. HRMS-ESI (m / z) calc'd for C9H 11 DN [M+H] +135.1027; found, 135.1025.

[0198] Example 36: Preparation of 8-methyl-1,2,3,4-tetrahydroquinoline-3-d

[0199]

[0200] Following the method of Example 35, 8-methylquinoline (14.3 mg, 0.10 mmol) was reacted as a starting material to obtain a yellow liquid 8-methyl-1,2,3,4-tetrahydroquinoline-3-d (12.1 mg, yield 82%). The product's R was measured on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 10:1). f = 0.3.

[0201] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 6.90 (dd, J =10.6, 7.5 Hz, 2H), 6.59 (t, J = 7.4 Hz, 1H), 3.40 (t, J = 5.5 Hz, 2H), 2.86 -2.81 (m, 2H), 2.11 (s, 3H), 1.99 - 1.95 (m, 1H) ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3, 23 ℃, δ ): 142.83, 127.96, 127.50, 121.29, 121.00, 116.52, 42.40,27.32, 21.93(t, J = 19.8 Hz), 17.26 ppm. 2 H{ 1 H} NMR (61 MHz, CH2Cl2, 23 ℃, δ ):1.90 ppm. HRMS-ESI (m / z) calc'd for C 10 H 13 DN [M+H] + 149.1184; found, 149.1181.

[0202] Example 37: Preparation of 6-methyl-1,2,3,4-tetrahydroquinoline-3-d

[0203]

[0204] Following the method of Example 35, 6-methylquinoline (14.3 mg, 0.10 mmol) was reacted as a starting material to obtain a yellow liquid 6-methyl-1,2,3,4-tetrahydroquinoline-3-d (12.4 mg, yield 84%). The product's R was measured on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 10:1). f = 0.3.

[0205] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 6.87 - 6.76(m, 2H), 6.44 (d, J = 8.5 Hz, 1H), 3.29 (t, J = 5.5 Hz, 2H), 2.76 (t, J = 6.5 Hz, 2H), 2.23 (s, 3H), 1.97 - 1.93 (m, 1H) ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3, 23 ℃, δ ): 142.49, 130.21, 127.37, 126.43, 121.77, 114.62, 42.24, 26.93,22,20 (t, J =19.5 Hz), 20.52 ppm. 2 H{ 1 H} NMR (61 MHz, CH2Cl2, 23 ℃, δ ): 1.88 ppm. HRMS-ESI(m / z) calc'd for C 10 H 13 DN [M+H] + 149.1184; found, 149.1180.

[0206] Example 38: Preparation of 7-methyl-1,2,3,4-tetrahydroquinoline-3-d

[0207]

[0208] Following the method of Example 35, 7-methylquinoline (14.3 mg, 0.10 mmol) was reacted as a starting material to obtain a yellow liquid 7-methyl-1,2,3,4-tetrahydroquinoline-3-d (10.7 mg, 72% yield). The product's R was measured on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 10:1). f = 0.3.

[0209] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 6.87 (d, J =7.5 Hz, 1H), 6.52 - 6.42 (m, 1H), 6.33 (s, 1H), 3.32 - 3.29 (m, 2H), 2.77 -2.74 (m, 2H), 2.24 (s, 3H), 1.98 - 1.92 (m, 1H) ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3, 23 ℃, δ ): 144.66, 136.50, 129.53, 118.73, 118.11, 114.94, 42.07,26.60, 22.15 (t, J = 19.9 Hz), 21.25 ppm. 2 H{ 1 H} NMR (61 MHz, CH2Cl2, 23 ℃, δ ):1.87 ppm. HRMS-ESI (m / z) calc'd for C 10 H 13 DN [M+H] + 149.1184; found, 149.1180.

[0210] Example 39: Preparation of 6-phenyl-1,2,3,4-tetrahydroquinoline-3-d

[0211]

[0212] Following the method of Example 35, 6-phenylquinoline (20.5 mg, 0.10 mmol) was reacted as a starting material to obtain a yellow liquid 6-phenyl-1,2,3,4-tetrahydroquinoline-3-d (12.6 mg, 60% yield). The product's R was measured on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 10:1). f = 0.3.

[0213] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 7.61 - 7.52(m, 2H), 7.41 (dd, J = 8.5, 7.0 Hz, 2H), 7.31 - 7.23 (m, 3H), 6.57 (d, J = 7.9Hz, 1H), 3.38 - 3.33 (m, 2H), 2.88 - 2.85 (m, 2H), 2.04 - 1.98 (m, 1H) ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3, 23 ℃, δ ): 144.38, 141.63, 130.04, 128.70, 128.31,126.38, 126.01, 125.64, 121.70, 114.56, 42.07, 27.15, 21.94 (t, J = 19.7 Hz)ppm. 2 H{ 1 H} NMR (61 MHz, CH2Cl2, 23 ℃, δ ): 1.94 ppm. HRMS-ESI (m / z) calc'd forC 15 H 15 DN [M+H] + 211.1340; found, 211.1335.

[0214] Example 40: Preparation of 6-(4-trifluoromethylphenyl)-1,2,3,4-tetrahydroquinoline-3-d

[0215]

[0216] Following the method of Example 35, 6-(4-trifluoromethylphenyl)quinoline (27.3 mg, 0.10 mmol) was reacted as a starting material to obtain a yellow liquid 6-(4-trifluoromethylphenyl)-1,2,3,4-tetrahydroquinoline-3-d (26.1 mg, 94% yield). The product was measured on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 10:1). f = 0.3.

[0217] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 7.65 - 6.63(m, 4H), 7.29 - 7.27 (m, 2H), 6.57 (d, J = 8.0 Hz, 1H), 3.40 - 3.37 (m, 2H), 2.88 - 2.85 (m, 2H), 2.02 - 1.98 (m, 1H) ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3, 23℃, δ ): 145.16, 145.05, 128.41, 128.10, 127.85 (q, J = 32.1 Hz), 126.29, 125.81,125.66 (q, J = 3.8 Hz), 124.68 (q, J = 270.0Hz), 121.74, 114.48, 41.97, 27.16,21.73 (t, J = 19.9 Hz) ppm. 19 F NMR (376 MHz, CDCl3, 23 ℃, δ): - 62.14 ppm. 2 H{ 1 H}NMR (61 MHz, CH2Cl2, 23 ℃, δ ): 1.96 ppm. HRMS-ESI (m / z) calc'd for C 16 H 14 DF3N[M+H] + 279.1214; found, 279.1206.

[0218] Example 41: Preparation of 6-(4-trifluoromethoxyphenyl)-1,2,3,4-tetrahydroquinoline-3-d

[0219]

[0220] Following the method of Example 35, 6-(4-trifluoromethoxyphenyl)quinoline (28.9 mg, 0.10 mmol) was reacted as a starting material to obtain a colorless solid 6-(4-trifluoromethoxyphenyl)-1,2,3,4-tetrahydroquinoline-3-d (24.7 mg, yield 84%). The product's R was measured on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 10:1). f = 0.3.

[0221] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 7.54 (d, J =8.7 Hz, 2H), 7.29 - 7.17 (m, 4H), 6.56 (d, J = 8.1 Hz, 1H), 3.39 - 3.36 (d, J =5.5 Hz, 2H), 2.87 - 2.82 (m, 2H), 2.02 - 1.98 (m, 1H) ppm. 13 C{ 1 H} NMR (100MHz, CDCl3, 23 ℃, δ ): 147.71 (q, J = 2.0 Hz), 144.69, 140.45, 128.46, 128.26,127.46, 125.60, 121.73, 121.26, 120.71 (q, J = 255.1 Hz), 114.51, 41.99, 27.13,21.80 (t, J = 19.7 Hz) ppm. 19 F NMR (376 MHz, CDCl3, 23 ℃, δ): - 57.84 ppm. 2 H{ 1 H} NMR (61 MHz, CH2Cl2, 23 ℃, δ ): 1.93 ppm. HRMS-ESI (m / z) calc'd forC 16 H 14 DF3NO [M+H] +295.1163; found, 295.1156.

[0222] Example 42: Preparation of 6-(furan-3-yl)-1,2,3,4-tetrahydroquinoline-3-d

[0223]

[0224] Following the method of Example 35, 6-(furan-3-yl)quinoline (19.5 mg, 0.10 mmol) was reacted as a starting material to yield a colorless solid (19.2 mg, 96% yield). The product's R was measured on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 10:1). f = 0.3.

[0225] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 7.62 (t, J =1.2 Hz, 1H), 7.45 (t, J = 1.7 Hz, 1H), 7.14 - 7.12 (m, 2H), 6.65 - 6.64 (m,1H), 6.52 - 6.50 (m, 1H), 3.36 - 3.31 (m, 2H), 2.83 - 2.80 (m, 2H), 2.01 -1.95 (m, 1H) ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3, 23 ℃, δ ): 144.03, 143.31,137.06, 127.22, 126.81, 124.64, 121.77, 121.30, 114.55, 108.96, 42.06, 27.04,21.91 (t, J = 19.7 Hz) ppm. 2 H{ 1 H} NMR (61 MHz, CH2Cl2, 23 ℃, δ ): 1.92 ppm.HRMS-ESI (m / z) calc'd for C 13 H 13 DNO [M+H] + 201.1133; found, 201.1129.

[0226] Example 43: Preparation of methyl-1,2,3,4-tetrahydroquinoline 6-carboxylate-3-d

[0227]

[0228] Following the method of Example 35, methylquinoline 6-carboxylate (18.7 mg, 0.10 mmol) was used as a starting material to obtain a colorless solid, methyl-1,2,3,4-tetrahydroquinoline 6-carboxylate-3-d (13.0 mg, yield 68%). The product's R was measured on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 10:1). f =0.3.

[0229] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 7.67 - 7.65(m, 2H), 6.41 (d, J = 8.9 Hz, 1H), 3.85 (s, 3H), 3.38 - 3.36 (m, 2H), 2.80 -2.77 (m, 2H), 1.96 - 1.91 (m, 1H) ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3, 23 ℃, δ ):167.66, 148.91, 131.44, 129.24, 120.02, 117.57, 112.74, 51.56, 41.76, 26.91,21.18 (t, J = 19.9 Hz) ppm. 2 H{ 1 H} NMR (61 MHz, CH2Cl2, 23 ℃, δ ): 1.89 ppm. HRMS-ESI (m / z) calc'd for C 11 H 13 DNO2[M+H] + 193.1082; found, 193.1080.

[0230] Example 44: Preparation of 1,2,3,4-tetrahydroquinoline 6-nitrile-3-d

[0231]

[0232] Following the method of Example 35, quinoline-6-onitrile (15.4 mg, 0.10 mmol) was used as a starting material to obtain a colorless solid, 1,2,3,4-tetrahydroquinoline-6-onitrile-3-d (11.9 mg, 75% yield). The product's R was measured on silica gel thin-layer chromatography using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 10:1). f = 0.3.

[0233] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 7.23 - 7.19(m, 2H), 6.41 (d, J = 8.2 Hz, 1H), 4.40 (s, 1H), 3.39 - 3.35 (m, 2H), 2.76 -2.71 (m, 2H), 1.97 - 1.91 (m, 1H) ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3, 23 ℃, δ ):148.36, 133.32, 131.37, 121.04, 120.96, 113.34, 97.77, 41.60, 26.73, 20.71(t, J = 19.8 Hz) ppm. 2 H{ 1 H} NMR (61 MHz, CH2Cl2, 23 ℃, δ ): 1.88 ppm. HRMS-ESI(m / z) calc'd for C 10 H 10 DN2[M+H] + 160.0980; found, 160.0976.

[0234] Example 45: Preparation of 1,2,3,4-tetrahydroquinoline-2,3,4-d3

[0235] The difference between this embodiment and Example 1 is that the nickel catalyst used and the yield data are as follows:

[0236]

[0237] Example 46: Preparation of 1,2,3,4-tetrahydroquinoline-2,3,4-d3

[0238] The difference between this embodiment and Embodiment 1 is that the deuterium source or ligand used is as follows:

[0239]

[0240] Example 47: Preparation of 1,2,3,4-tetrahydroquinoline-2,3,4-d3

[0241] The difference between this embodiment and Embodiment 1 is that the ligands used and the yield data are as follows:

[0242]

[0243] Example 48: Preparation of 1,2,3,4-tetrahydroquinoline-2,4-d2

[0244] The difference between this embodiment and Embodiment 17 is that the conditions used and the yield data are as follows:

[0245]

[0246] Example 49: Preparation of 1,2,3,4-tetrahydroquinoline-3-d

[0247] The difference between this embodiment and Embodiment 35 is that the conditions used and the yield data are as follows:

[0248]

[0249] Application of the method of this invention in the deuteration modification of quinfamit:

[0250] Application Example 1: Preparation of deuterated quinacrine famit-d3(5q)

[0251]

[0252] Following the method of Example 1, tert-butylquinoline-6-yl carbonate (122.5 mg, 0.50 mmol) was used as a starting material to yield a colorless solid product 2q (103.5 mg, 82% yield). The product's R was measured on a silica gel thin-layer plate using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 10:1). f = 0.2.

[0253] Add 2q (252.3 mg, 1.0 mmol) to a dry Schlenk tube, followed by chloroacetyl chloride (ClCH2COCl, 115.4 μL, 1.20 mmol), triethylamine (Et3N, 417.0 μL, 3.0 mmol) and dichloromethane (DCM, 3 mL) in sequence, and stir the solution overnight at room temperature. After the reaction was complete, the reaction mixture was extracted with DCM (3 times), the organic phases were combined, dried over anhydrous sodium sulfate (Na2SO4), and concentrated by vacuum filtration (3q). Trifluoroacetic acid (TFA, 0.50 mL) and DCM (3 mL) were then added, and the mixture was stirred at room temperature for 3 hours. The pH was then adjusted to 14 with aqueous sodium hydroxide solution, and the mixture was extracted with DCM (3 times). The organic phases were combined and concentrated to 3 mL (4q). 2-Furfuryl chloride (197.2 mg, 2.0 mmol) and triethylamine (417.0 μL, 3.0 mmol) were then added, and the mixture was stirred overnight at room temperature. After concentration by vacuum filtration, the final product 5q was purified by silica gel column chromatography. The R of the product was measured on a silica gel thin-layer plate using hexane-ethyl acetate as the developing solvent (hexane to ethyl acetate volume ratio 5:1). f = 0.2.

[0254] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 7.71 (d, J =1.7 Hz, 1H), 7.41 (d, J = 3.6 Hz, 1H), 7.28 (s, 1H), 7.14 (s, 2H), 6.63 (dd, J =3.6, 1.7 Hz, 1H), 6.49 (s, 1H), 3.87 (d, J = 7.6 Hz, 1H), 2.76 (s, 1H), 2.04(s, 1H) ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3, 23 ℃, δ ): 164.12, 156.84, 148.63,147.57, 143.70, 136.28, 135.48, 124.00, 122.32, 120.34, 120.01, 112.43,64.01, 44.07, 26.50 - 26.17 (m), 23.16 -22.92 (m) ppm. 2 H{ 1H} NMR (61 MHz, CH2Cl2, 23 ℃, δ ): 3.86, 2.78, 2.02 ppm. HRMS-ESI (m / z) calc'd for C 16 H 11 D3Cl2NO4[M+H] + 357.0482; found, 357.0475.

[0255] Application Example 2: Preparation of deuterated quinacrine famit-d2 (9q)

[0256]

[0257] Under an argon atmosphere, NiI₂ (62.5 mg, 0.1 mmol), sarcosine (17.8 mg, 0.2 mmol), NaBD₄ (83.7 mg, 2.0 mmol), and acetonitrile (2.50 mL) were added sequentially to a reaction flask equipped with a magnetic stirrer. Then, tert-butylquinoline-6-yl carbonate (122.5 mg, 0.50 mmol) and 2,2,3,3,4,4,5,5-octafluoro-1-pentanol (232.0 mg, 1.0 mmol) were added. The reaction mixture was stirred at 20 °C for 12 hours under 390 nm LEDs (10 W). After the reaction was complete, 5.0 mL of methanol was added to quench the reaction. The reaction mixture was transferred to a flask containing ethyl acetate, and volatile solvents were removed by vacuum distillation. The residue was purified by silica gel column chromatography to give a white solid 6q (100.3 mg, 80%). Using hexane-ethyl acetate as the developing solvent (volume ratio of hexane to ethyl acetate 10:1) on silica gel thin-layer plates, the Rf of the product was measured to be 0.2.

[0258] Following the method in Application Example 1, compound 6q was reacted as a starting material to obtain the final product 9q. The R0 of the product was measured on a silica gel thin-layer plate using n-hexane-ethyl acetate as the developing solvent (n-hexane to ethyl acetate volume ratio of 5:1). f = 0.2.

[0259] The structural characterization data of the product are as follows: 1 H NMR (400 MHz, CDCl3, 23 ℃, δ ): 7.62 (d, J =1.7 Hz, 1H), 7.32 (d, J = 3.5 Hz, 1H), 7.17 (s, 1H), 7.05 (s, 2H), 6.54 (dd, J= 3.5, 1.8 Hz, 1H), 6.40 (s, 1H), 3.77 (d, J = 7.1 Hz, 1H), 2.67 (s, 1H), 2.08- 1.83 (m, 2H) ppm. 13 C{ 1 H} NMR (100 MHz, CDCl3, 23 ℃, δ ): 164.00, 156.74,148.54, 147.51, 143.57, 136.25, 135.34, 123.91, 122.22, 120.24, 119.93,112.36, 63.97,44.18 - 43.17(m), 26.34 - 25.94(m), 23.06 ppm. 2 H{ 1 H} NMR (61MHz, CH2Cl2, 23 ℃, δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ ): 3.85, 2.79 ppm. HRMS-ESI (m / z) calc'd for C 16 H 12 D₂Cl₂NO₄[M+H] + 356.0420; found, 356.0418.

[0260] The above detailed embodiments describe the implementation of the present invention; however, the present invention is not limited to the specific details described in the above embodiments. Within the scope of the claims and technical concept of the present invention, various simple modifications and changes can be made to the technical solution of the present invention, and these simple modifications all fall within the protection scope of the present invention.

Claims

1. A method for selective quantitative reduction of deuterated quinoline at a nickel catalytic site, characterized in that, Materials including quinoline heterocyclic compounds, nickel catalysts, ligands, borodeuterides / boronhydrides, and deuterium / hydrogen sources are mixed in an organic solvent and reacted under light irradiation to obtain deuterated quinoline heterocyclic compounds. One of the reaction equations is shown below: （1） ； （2） ； （3） ； （4） ； In the formula, R and R' are each independently selected from at least one of hydrogen, halogen, cyano, hydroxyl, trifluoromethyl, alkyl, alkoxy, aryloxy, acyloxy, ester, acyl, thiophene, oxazolyl, substituted or unsubstituted phenyl, amide, substituted or unsubstituted phenyl group.

2. The method for selective quantitative reduction of deuterated quinoline at nickel catalytic sites according to claim 1, characterized in that, The molar ratio of the quinoline heterocyclic compound, nickel catalyst, ligand, borodeuteride / boronhydride, and deuterium source / hydrogen source is 1:(0.05~1):(0.05~1):(0.8~3):(0.5~3).

3. The method for selective quantitative reduction of deuterated quinoline at nickel catalytic sites according to claim 2, characterized in that, The borodeuteride is selected from at least one of sodium borodeuteride, lithium borodeuteride, sodium cyanoborodeuteride, and sodium triethylborodeuteride; the borohydride is selected from at least one of sodium borohydride, lithium borohydride, sodium cyanoborodeuteride, and sodium triethylborohydride.

4. The method for selective quantitative reduction of deuterated quinoline at nickel catalytic sites according to claim 2, characterized in that, The ligand is selected from at least one of the following structures: 。 5. The method for selective quantitative reduction of deuterated quinoline at nickel catalytic sites according to claim 2, characterized in that, The deuterium source is selected from at least one of deuterated hydrochloric acid, deuterated ethanol, deuterated tert-butanol, deuterated phosphoric acid, and deuterated boric acid; the hydrogen source is 2,2,3,3,4,4,5,5-octafluoropentanol.

6. The method for selective quantitative reduction of deuterated quinoline at nickel catalytic sites according to any one of claims 1, characterized in that, Materials including quinoline heterocyclic compounds, nickel catalysts, ligands, borodeuterides, and deuterium sources were mixed in an organic solvent and reacted under light irradiation to obtain deuterated quinoline heterocyclic compounds -d3. The reaction equation is as follows: ,or .

7. The method for selective quantitative reduction of deuterated quinoline at nickel catalytic sites according to any one of claims 1, characterized in that, Materials including quinoline heterocyclic compounds, nickel catalysts, ligands, borodeuterides, and hydrogen sources are mixed in an organic solvent and reacted under light irradiation to yield deuterated quinoline heterocyclic compounds -d2. One of the reaction equations is shown below: （1） ； （2） ； （3） ； （4） 。 8. The method for selective quantitative reduction of deuterated quinoline at nickel catalytic sites according to any one of claims 1, characterized in that, Materials including quinoline heterocyclic compounds, nickel catalysts, ligands, borohydrides, and deuterium sources were mixed in an organic solvent and reacted under light irradiation to obtain deuterated quinoline heterocyclic compounds -d1. The reaction equation is as follows: ,or .

9. The method for selective quantitative reduction of deuterated quinoline at the nickel catalytic site according to any one of claims 1-8, characterized in that, The materials also include potassium persulfate, with a molar amount 1 to 3 times that of quinoline heterocyclic compounds.

10. The use of the method according to any one of claims 1-8 in the deuteration modification of drug molecules.

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