Preparation method of a pyrido[1,2-a]indole compound

Abstract

A method for preparing pyrido[1,2-a]indole compounds. The present invention belongs to the technical field of photocatalytic synthesis, and specifically relates to a method for synthesizing pyrido[1,2,a]indole compounds. The present invention aims to solve the technical problem that the existing methods for synthesizing pyrido[1,2,a]indole compounds require the introduction of photocatalysts or metal catalysts, resulting in complex substrates and difficult separation. Method: An N-substituted indole compound and a Umemoto reagent are added to a solvent to obtain a mixed solution, and the mixed solution is irradiated with visible light at room temperature under an inert gas atmosphere to obtain a pyrido[1,2-a]indole compound. The present invention adopts a simple, efficient and green photocatalytic synthesis strategy to achieve the synthesis of pyrido[1,2-a]indole compounds without the addition of external photocatalysts and oxidants. The reaction operation is simple, the conditions are mild, and the functional group compatibility is good. The method of the present invention is used for synthesizing pyrido[1,2-a]indole compounds.

Description

Technical Field

[0001] The present invention belongs to the technical field of photocatalytic synthesis, and specifically relates to a method for synthesizing pyrido[1,2,a]indole compounds. Background Art

[0002] Nitrogen-containing heterocyclic skeletons widely exist in bioactive natural products and drug molecules. Among them, the exploration of the synthesis method of the pyrido[1,2-a]indole structure has important research value. At present, most of the synthesis methods for pyrido[1,2-a]indole derivatives require polycyclic compounds such as indole and indolizine as starting materials. Pyrido[1,2-a]indole compounds have received extensive attention due to their excellent pharmacological activities. How to construct pyrido[1,2-a]indole compounds is one of the hot research contents in the field of organic synthetic chemistry. At present, pyrido[1,2-a]indole compounds can be successfully synthesized through trifluoromethyl. However, the introduction of trifluoromethyl has a great impact on the molecular properties, such as increasing metabolic stability, polarity, solubility, etc. In addition, photocatalytic trifluoromethylation reactions often require the additional addition of photocatalysts or transition metal catalysts, resulting in adverse consequences such as increased production costs, metal ion residues, and separation difficulties. Summary of the Invention

[0003] The present invention aims to solve the technical problem that the existing methods for synthesizing pyrido[1,2,a]indole compounds require the introduction of photocatalysts or metal catalysts, resulting in complex substrates and difficult separation, and provides a method for preparing pyrido[1,2-a]indole compounds.

[0004] A method for preparing pyrido[1,2-a]indole compounds is specifically prepared according to the following steps:

[0005] I. Add N-substituted indole compounds and Umemoto reagents into a quartz reaction tube filled with a solvent;

[0006] II. Under a nitrogen atmosphere and at room temperature, place the reaction tube in step I under a blue light lamp for a photocatalytic reaction;

[0007] III. Rotavaporize the mixed solution obtained from the reaction in step II to obtain a crude product;

[0008] IV. Subject the crude product obtained in step III to column chromatography separation to obtain the pyrido[1,2-a]indole compound, and complete the preparation.

[0009] Further, the structural formula of the N-substituted indole compound in step I is as follows:

[0010]

[0011] In the formula, R 1 , R 2 , R 3 , R 4 and R 5 are all H;

[0012] Or one of R 1 , R 3 and R 5 is CH 3 , and the rest are all H;

[0013] Or one of R 1 and R 4 is COOCH 3 , and the rest are all H;

[0014] Or R 2 is CN, and the rest are all H.

[0015] Furthermore, the Umemoto reagent described in Step 1 is a trifluoromethyl reagent, and its structural formula is as follows:

[0016]

[0017] Furthermore, the solvent described in Step 1 is dichloromethane.

[0018] The preparation reaction formula of the N-substituted indole compound is as follows:

[0019]

[0020] wherein R includes R 1 , R 2 , R 3 , R 4 and R 5 ;

[0021] R 1 , R 2 , R 3 , R 4 and R 5 are all H;

[0022] Or one of R 1 , R 3 and R 5 is CH 3 , and the rest are all H;

[0023] Or one of R 1 and R 4 is COOCH 3 , and the rest are all H;

[0024] Or R 2It is CN, and the rest are all H.

[0025] The reaction formula of the present invention is as follows:

[0026]

[0027] The present invention does not require a photocatalyst and a metal catalyst, and the reaction can occur directly under light irradiation. The operation is simple and the substrate applicability is good.

[0028] The present invention takes N-substituted indole 1a (R 1 , R 2 , R 3 , R 4 and R 5 are all H) as an example, and the reaction mechanism is as follows:

[0029]

[0030] N-substituted indole 1a polymerizes under light irradiation to become oligomer poly-1a, which can absorb light to initiate the reaction. The homolytic cleavage of the S-CF 3 bond in trifluoromethyl reagent 2a under light irradiation is possible, but it is not the main pathway (the bond energy of S-CF3 is relatively large). It is more likely to obtain electrons from the oligomer to generate trifluoromethyl radical and dibenzothiophene 4. The trifluoromethyl radical is intercepted by the double bond in substrate 1a, and the radical transfer occurs, followed by an intramolecular cyclization reaction of 6-exo-trig; the radical 6 in the ring is oxidized by trifluoromethyl reagent 2a or by the electron-losing oligomer to become a C + ion 7, and a proton is removed to restore aromaticity, obtaining the target product 3a.

[0031] Advantages of the present invention:

[0032] The present invention synthesizes this type of compound for the first time, and uses a radical cascade cyclization strategy to form two bonds in one step to construct a new six-membered ring. The present invention adopts a simple, efficient and green photocatalytic synthesis strategy to realize the synthesis of pyrido[1,2-a]indole compounds under the condition of no external photocatalyst and oxidant. The reaction operation is simple, the conditions are mild, and the functional group compatibility is good. Compared with the prior art, it has the following advantages:

[0033] (1), A radical cascade cyclization reaction occurs without a photocatalyst and a metal catalyst to construct an indole-fused ring product with a trifluoromethyl group, reducing costs, avoiding possible metal residues, and simplifying the method

[0034] (2), The reaction substrates are all cheap and easy to synthesize, the substrate range is wide, the obtained products are easy to separate, and the reaction is efficient.

[0035] The method of the present invention is used to synthesize pyrido[1,2-a]indole compounds. Description of the Drawings

[0036] Figure 1 The spectral diagram of pyrido[1,2-a]indole compound 3c prepared in Example 3;

[0037] Figure 2 The carbon spectral diagram of pyrido[1,2-a]indole compound 3c prepared in Example 3;

[0038] Figure 3 The fluorine spectral diagram of pyrido[1,2-a]indole compound 3c prepared in Example 3;

[0039] Figure 4 The hydrogen spectral diagram of pyrido[1,2-a]indole compound 3f prepared in Example 6;

[0040] Figure 5 The carbon spectral diagram of pyrido[1,2-a]indole compound 3f prepared in Example 6;

[0041] Figure 6 The fluorine spectral diagram of pyrido[1,2-a]indole compound 3f prepared in Example 6. Detailed Description of the Invention

[0042] Detailed Description of the Invention 1: The preparation method of a pyrido[1,2-a]indole compound in this embodiment is specifically prepared according to the following steps:

[0043] 1. Add the N-substituted indole compound and the Umemoto reagent into a quartz reaction tube filled with a solvent;

[0044] 2. Under the nitrogen atmosphere and at room temperature, place the reaction tube in step 1 under a blue light for a photochemical reaction;

[0045] 3. Rotavaporize the mixed solution obtained from the reaction in step 2 to obtain a crude product;

[0046] 4. Subject the crude product obtained in step 3 to column chromatography separation to obtain the pyrido[1,2-a]indole compound, and the preparation is completed.

[0047] Detailed Description of the Invention 2: The difference between this embodiment and Detailed Description of the Invention 1 is that the structural formula of the N-substituted indole compound in step 1 is as follows:

[0048]

[0049] In the formula, R 1 , R 2 , R 3 , R 4 and R 5 are all H;

[0050] or R 1 、R 3 and R 5 One of them is CH 3 , and the rest are all H;

[0051] or R 1 and R 4 One of them is COOCH 3 , and the rest are all H;

[0052] or R 2 is CN, and the rest are all H. Others are the same as in the first specific implementation manner.

[0053] Specific implementation manner three: The difference between this implementation manner and the first or second specific implementation manner is that: The Umemoto reagent described in step one is a trifluoromethyl reagent, and its structural formula is as follows:

[0054] Others are the same as in the first or second specific implementation manner.

[0055] Specific implementation manner four: The difference between this implementation manner and any one of the first to third specific implementation manners is that: The solvent described in step one is dichloromethane. Others are the same as any one of the first to third specific implementation manners.

[0056] Specific implementation manner five: The difference between this implementation manner and any one of the first to fourth specific implementation manners is that: In step one, the dosage ratio of the N-substituted indole compound to the solvent is 0.28 - 0.32 mmol: 1 - 1.5 mL;

[0057] The dosage ratio of the Umemoto reagent to the solvent is 0.08 - 0.12 mmol: 1 - 1.5 mL. Others are the same as any one of the first to fourth specific implementation manners.

[0058] Specific implementation manner six: The difference between this implementation manner and any one of the first to fifth specific implementation manners is that: In step one, the dosage ratio of the N-substituted indole compound to the solvent is 0.3 mmol: 1.5 mL;

[0059] The dosage ratio of the Umemoto reagent to the solvent is 0.1 mmol: 1.5 mL. Others are the same as any one of the first to fifth specific implementation manners.

[0060] Specific implementation manner seven: The difference between this implementation manner and any one of the first to sixth specific implementation manners is that: During the light reaction in step two, the wavelength of the blue light lamp is 440 - 460 nm, and the irradiation time is 12 - 14 h. Others are the same as any one of the first to sixth specific implementation manners.

[0061] Embodiment VIII: The difference between this embodiment and any one of Embodiments I - VII is that in Step 3, rotary evaporation treatment is carried out using a rotary evaporator. Others are the same as any one of Embodiments I - VII.

[0062] Embodiment IX: The difference between this embodiment and any one of Embodiments I - VIII is that for the column chromatography separation treatment in Step 4, silica gel and a mobile phase are used, where the mobile phase is a mixture of petroleum ether and ethyl acetate. Others are the same as any one of Embodiments I - VIII.

[0063] Embodiment X: The difference between this embodiment and any one of Embodiments I - IX is that petroleum ether and ethyl acetate are mixed at a volume ratio of 20:1. Others are the same as any one of Embodiments I - IX.

[0064] The content of the present invention is not limited to the content of the above embodiments. The combination of one or several of the specific embodiments can also achieve the purpose of the invention.

[0065] Example 1:

[0066] A method for preparing a pyrido[1,2 - a]indole compound in this example is specifically prepared according to the following steps:

[0067] I. Add 0.3 mmol of N - substituted indole compound and 0.1 mmol of Umemoto reagent into a quartz reaction tube containing 1.5 mL of anhydrous DCM (dichloromethane) as the solvent;

[0068] The structural formula of the N - substituted indole compound is as follows:

[0069]

[0070] In the formula, R 1 , R 2 , R 3 , R 4 and R 5 are all H;

[0071] II. After degassing, place the reaction tube in Step I under a blue - light lamp in a nitrogen atmosphere at room temperature for a photo - reaction; the wavelength of the blue - light lamp is 450 nm, and the irradiation time is 12 h;

[0072] III. Carry out rotary evaporation treatment on the mixed solution obtained from the reaction in Step II using a rotary evaporator to obtain a crude product;

[0073] IV. Determine the polarity of the eluent for column chromatography by spotting on a plate, and carry out column chromatography separation treatment on the crude product obtained in Step III, where the mobile phase is a mixture of petroleum ether and ethyl acetate at a volume ratio of 20:1 to obtain the pyrido[1,2 - a]indole compound, thus completing the preparation.

[0074] In this reaction, the by-product diphenyl sulfide has the lowest polarity, followed by the remaining substrate, and the polarity of the trifluoromethylated product increases compared to the raw material. The reaction yield is 72%, and the product is a white solid.

[0075] The NMR data of the pyrido[1,2-a]indole compound 3a obtained in this example are as follows: 1 H NMR(400MHz,CDCl 3 )δ8.49–8.44(m,1H),7.53–7.46(m,1H),7.36–7.27(m,2H),6.40(d,J=1.6Hz,1H),3.37(tt,J=10.3,4.8Hz,1H),2.98–2.75(m,3H),2.52–2.32(m,2H),1.95(dtd,J=13.2,10.8,4.6Hz,1H). 13 C NMR(101MHz,CDCl 3 )δ168.57,139.31,135.22,129.18,124.96,124.29,120.17,116.56,105.18,37.52,37.23,32.96,29.44,29.41,26.95. 19 F NMR(376MHz,CDCl 3 )δ-63.27.

[0076] Example 2:

[0077] A preparation method of a pyrido[1,2-a]indole compound in this example is specifically prepared according to the following steps:

[0078] 1. Add 0.3 mmol of N-substituted indole compound and 0.1 mmol of Umemoto reagent to a quartz reaction tube containing 1.5 mL of anhydrous DCM (dichloromethane) as the solvent;

[0079] The structural formula of the N-substituted indole compound is as follows:

[0080]

[0081] In the formula, R 1 is CH 3 , R 2 , R 3 , R 4 and R 5 are all H;

[0082] II. After degassing, place the reaction tube in Step I under a nitrogen atmosphere at room temperature under a blue light for a photochemical reaction; the wavelength of the blue light is 450 nm and the irradiation time is 12 h.

[0083] III. Subject the mixture obtained from the reaction in Step II to rotary evaporation using a rotary evaporator to obtain a crude product.

[0084] IV. Determine the polarity of the eluent for column chromatography by TLC, and subject the crude product obtained in Step III to column chromatography separation, wherein the mobile phase is a mixture of petroleum ether and ethyl acetate at a volume ratio of 20:1, to obtain the said pyrido[1,2-a]indole compound, thus completing the preparation.

[0085] In this reaction, the by-product diphenyl sulfide has the lowest polarity, the remaining substrate has the second lowest polarity, and the polarity of the trifluoromethylated product is increased compared to the starting material. The reaction yield is 70%, and the product is a white solid.

[0086] The NMR data of the pyrido[1,2-a]indole compound 3b obtained in this example are as follows: 1 H NMR(400MHz,CDCl 3 )δ8.45(d,J=8.2Hz,1H),7.46(d,J=7.5Hz,1H),7.32(p,J=7.3Hz,2H),3.68(d,J=4.4Hz,1H),2.95–2.74(m,2H),2.58–2.27(m,2H),2.24(d,J=6.7Hz,5H). 13 C NMR(101MHz,CDCl 3 )δ168.09,134.62,133.96,130.74,127.59,125.10,124.84,124.10,118.31,116.61,113.64,77.41,77.09,76.78,36.75,36.47,36.20,35.92,29.76,29.36,25.42,25.39,24.63,8.45. 19 F NMR(376MHz,CDCl 3 )δ-64.18.

[0087] Example III:

[0088] The preparation method of a pyrido[1,2-a]indole compound in this example is specifically carried out according to the following steps:

[0089] I. Add 0.3 mmol of N-substituted indole compound and 0.1 mmol of Umemoto reagent to a quartz reaction tube containing 1.5 mL of anhydrous DCM (dichloromethane) as the solvent.

[0090] The structural formula of the N-substituted indole compound is as follows:

[0091]

[0092] In the formula, R 1 is CO 2 Me, R 2 , R 3 , R 4 and R 5 are all H;

[0093] II. After degassing, under a nitrogen atmosphere and at room temperature, place the reaction tube in Step I under a blue light for a photoirradiation reaction; the wavelength of the blue light is 450 nm, and the irradiation time is 12 h;

[0094] III. Perform rotary evaporation on the mixed solution obtained from the reaction in Step II to obtain a crude product;

[0095] IV. Determine the polarity of the column chromatography eluent by thin-layer chromatography, and perform column chromatography separation on the crude product obtained in Step III, wherein the mobile phase is a mixture of petroleum ether and ethyl acetate with a volume ratio of 20:1, to obtain the pyrido[1,2-a]indole compound, thus completing the preparation.

[0096] In this reaction, the by-product diphenyl sulfide has the lowest polarity, the remaining substrate has the second lowest polarity, and the polarity of the trifluoromethylated product increases compared to the raw material. The reaction yield is 51%, and the product is a white solid.

[0097] The NMR data of the pyrido[1,2-a]indole compound 3c obtained in this example are as follows: 1 H NMR(400MHz,CDCl 3 )δ8.53–8.47(m,1H),8.15–8.09(m,1H),7.42–7.36(m,2H),4.45(d,J=11.1Hz,1H),3.99(s,3H),2.99–2.86(m,2H),2.75–2.61(m,1H),2.56–2.43(m,1H),2.37(d,J=14.3Hz,1H),2.27(d,J=13.4Hz,1H). 13 C NMR(101MHz,CDCl 3) δ 168.65, 164.74, 146.64, 134.64, 127.42, 126.77, 125.92, 125.31, 124.65, 121.56, 116.54, 109.21, 77.40, 77.08, 76.77, 51.71, 35.30, 35.02, 34.74, 34.46, 29.33, 27.15, 27.12, 22.73. 19 F NMR (376 MHz, CDCl 3 ) δ -63.62.

[0098] Example 4:

[0099] In this example, a method for preparing a pyrido[1,2-a]indole compound is specifically prepared according to the following steps:

[0100] I. Add 0.3 mmol of N-substituted indole compound and 0.1 mmol of Umemoto reagent into a quartz reaction tube containing 1.5 mL of anhydrous DCM (dichloromethane) as the solvent;

[0101] The structural formula of the N-substituted indole compound is as follows:

[0102]

[0103] In the formula, R 1 is CN, and R 2 , R 3 , R 4 and R 5 are all H;

[0104] II. After degassing, place the reaction tube in step I under a blue light at room temperature in a nitrogen atmosphere for a photoirradiation reaction; the wavelength of the blue light is 450 nm, and the irradiation time is 12 h;

[0105] III. Rotate and evaporate the mixed solution obtained from the reaction in step II using a rotary evaporator to obtain a crude product;

[0106] IV. Determine the polarity of the column chromatography eluent by TLC, and subject the crude product obtained in step III to column chromatography separation, wherein the mobile phase is a mixture of petroleum ether and ethyl acetate with a volume ratio of 20:1 to obtain the pyrido[1,2-a]indole compound, and the preparation is completed.

[0107] In this reaction, the by-product diphenyl sulfide has the lowest polarity, the remaining substrate has the second lowest polarity, and the polarity of the trifluoromethylated product increases compared to the raw material. The reaction yield is 42%, and the product is a white solid.

[0108] The 3D NMR data of the pyrido[1,2-a]indole compound obtained in this example:1 1H NMR (400 MHz, CDCl 3 ) δ 8.68 (d, J = 8.6 Hz, 1H), 7.59 (d, J = 7.6 Hz, 1H), 7.38 (t, J = 8.0 Hz, 1H), 6.65 (s, 1H), 3.44 (dt, J = 10.0, 5.2 Hz, 1H), 3.01–2.81 (m, 3H), 2.58–2.39 (m, 2H), 2.01 (dtd, J = 13.6, 11.1, 4.5 Hz, 1H). 13 13C NMR (101 MHz, CDCl 3 ) δ 168.55, 142.48, 135.02, 131.29, 128.46, 124.91, 124.79, 124.05, 121.01, 117.68, 103.35, 37.62, 37.33, 37.04, 36.76, 32.93, 31.50, 30.25, 29.61, 26.71. 19 19F NMR (376 MHz, CDCl 3 ) δ -63.23.

[0109] Example 5:

[0110] A preparation method of a pyrido[1,2-a]indole compound in this example is specifically prepared according to the following steps:

[0111] I. Add 0.3 mmol of N-substituted indole compound and 0.1 mmol of Umemoto reagent to a quartz reaction tube containing 1.5 mL of anhydrous DCM (dichloromethane) as the solvent;

[0112] The structural formula of the N-substituted indole compound is as follows:

[0113]

[0114] In the formula, R 3 is CH 3 , R 1 , R 2 , R 4 and R 5 are all H;

[0115] II. After degassing, place the reaction tube in step I under a blue light at room temperature in a nitrogen atmosphere for a photoirradiation reaction; the wavelength of the blue light is 450 nm, and the irradiation time is 12 h;

[0116] III. Perform rotary evaporation on the mixed solution obtained from the reaction in step II to obtain a crude product;

[0117] IV. Determine the polarity of the eluent for column chromatography by TLC, and subject the crude product obtained in Step III to column chromatography separation, wherein the mobile phase is a mixture of petroleum ether and ethyl acetate with a volume ratio of 20:1, to obtain the said pyrido[1,2-a]indole compound, thus completing the preparation.

[0118] In this reaction, the by-product diphenyl sulfide has the lowest polarity, the remaining substrate has the second lowest polarity, and the polarity of the trifluoromethylated product increases compared to the raw material. The reaction yield is 79%, and the product is a white solid.

[0119] The NMR data of the pyrido[1,2-a]indole compound 3e obtained in this example are as follows: 1 H NMR(400MHz,CDCl 3 )δ8.32(d,J=8.4Hz,1H),7.28(s,1H),7.14(d,J=8.3Hz,1H),6.31(s,1H),3.33(dt,J=9.7,5.2Hz,1H),2.92–2.72(m,3H),2.44(s,3H),2.43–2.31(m,2H),1.93(td,J=13.4,12.1,4.5Hz,1H). 13 C NMR(101MHz,CDCl 3 )δ168.39,139.34,133.89,133.37,129.42,127.81,126.16,125.05,120.16,116.15,104.94,77.41,77.10,76.78,37.75,37.47,37.19,36.91,32.87,31.56,30.20,29.76,29.41,29.38,26.96,21.48. 19 F NMR(376MHz,CDCl 3 )δ-63.26.

[0120] Example VI:

[0121] The preparation method of a pyrido[1,2-a]indole compound in this example is specifically carried out according to the following steps:

[0122] I. Add 0.3 mmol of N-substituted indole compound and 0.1 mmol of Umemoto reagent to a quartz reaction tube containing 1.5 mL of anhydrous DCM (dichloromethane) as the solvent;

[0123] The structural formula of the said N-substituted indole compound is as follows:

[0124]

[0125] Wherein, R 4 is CO 2 Me, R 1 , R 2 , R 3 and R 5 are all H;

[0126] II. After degassing, under a nitrogen atmosphere and at room temperature, place the reaction tube in step I under a blue light lamp for a photoreaction; the wavelength of the blue light lamp is 450 nm, and the irradiation time is 12 h;

[0127] III. Perform rotary evaporation on the mixed solution obtained from the reaction in step II to obtain a crude product;

[0128] IV. Determine the polarity of the column chromatography eluent by thin-layer chromatography, and perform column chromatography separation on the crude product obtained in step III, wherein the mobile phase is a mixture of petroleum ether and ethyl acetate with a volume ratio of 20:1, to obtain the pyrido[1,2-a]indole compound, and the preparation is completed.

[0129] In this reaction, the by-product diphenyl sulfide has the lowest polarity, the remaining substrate is the second, and the polarity of the trifluoromethylated product increases compared to the raw material. The reaction yield is 66%, and the product is a white solid.

[0130] The NMR data of the pyrido[1,2-a]indole compound 3f obtained in this example: 1 H NMR (400 MHz, CDCl 3 ) δ 9.10 (s, 1H), 7.97 (d, J = 8.2 Hz, 1H), 7.51 (d, J = 8.2 Hz, 1H), 6.43 (s, 1H), 3.94 (s, 3H), 3.39 (dt, J = 9.9, 5.2 Hz, 1H), 2.98–2.80 (m, 3H), 2.50–2.35 (m, 2H), 1.98 (qd, J = 12.0, 5.2 Hz, 1H). 13 C NMR (101 MHz, CDCl 3 ) δ 168.29, 167.49, 142.48, 134.58, 132.88, 130.39, 127.63, 126.58, 125.56, 124.87, 122.11, 119.78, 118.05, 104.97, 77.37, 77.05, 76.73, 52.12, 37.62, 37.34, 37.05, 36.77, 32.83, 29.49, 26.72. 19 F NMR (376 MHz, CDCl 3 ) δ -63.28.

[0131] Example VII:

[0132] In this example, a method for preparing pyrido[1,2-a]indole compounds is specifically carried out according to the following steps:

[0133] I. Add 0.3 mmol of N-substituted indole compound and 0.1 mmol of Umemoto reagent into a quartz reaction tube containing 1.5 mL of anhydrous DCM (dichloromethane) as the solvent;

[0134] The structural formula of the N-substituted indole compound is as follows:

[0135]

[0136] In the formula, R 5 is CH 3 , and R 1 , R 2 , R 3 and R 4 are all H;

[0137] II. After degassing, place the reaction tube in step I under a blue light lamp in a nitrogen atmosphere at room temperature for a photoirradiation reaction; the wavelength of the blue light lamp is 450 nm, and the irradiation time is 12 h;

[0138] III. Perform rotary evaporation on the mixed solution obtained from the reaction in step II to obtain a crude product;

[0139] IV. Determine the polarity of the column chromatography eluent by TLC, and perform column chromatography separation on the crude product obtained in step III. The mobile phase is a mixture of petroleum ether and ethyl acetate with a volume ratio of 20:1 to obtain the pyrido[1,2-a]indole compound, thus completing the preparation.

[0140] In this reaction, the by-product diphenyl sulfide has the lowest polarity, the remaining substrate has the second lowest polarity, and the polarity of the trifluoromethylated product increases compared to the raw material. The reaction yield is 30%, and the product is a white solid.

[0141] The NMR data of 3 g of the pyrido[1,2-a]indole compound obtained in this example are as follows: 1 H NMR(400MHz,CDCl 3)δ 7.32 (d, J = 7.6 Hz, 1H), 7.20 (t, J = 7.5 Hz, 1H), 7.13 (d, J = 7.4 Hz, 1H), 6.40 (s, 1H), 3.36 (dt, J = 9.7, 5.2 Hz, 1H), 2.93 (dt, J = 17.4, 4.9 Hz, 1H), 2.86–2.75 (m, 2H), 2.62 (s, 3H), 2.41 (ddd, J = 17.8, 14.0, 7.7 Hz, 2H), 2.05–1.90 (m, 1H). 13 C NMR (101 MHz, CDCl 3 )δ 167.95, 140.98, 135.11, 131.00, 130.56, 128.27, 127.81, 127.08, 125.05, 124.78, 122.29, 117.85, 106.01, 77.42, 77.10, 76.78, 37.99, 37.70, 37.42, 37.14, 33.55, 29.93, 26.94, 23.05. 19 FNMR (376 MHz, CDCl 3 )δ -63.27。

Claims

1. A method for preparing a pyrido[1,2-a]indole compound, characterized in that the method is specifically prepared according to the following steps: I. Add an N-substituted indole compound and Umemoto reagent into a quartz reaction tube containing a solvent; II. Under a nitrogen atmosphere and at room temperature, place the reaction tube in step I under a blue light lamp for a photoirradiation reaction; III. Rotavaporize the mixed solution obtained from the reaction in step II to obtain a crude product; IV. Subject the crude product obtained in step III to column chromatography separation to obtain the pyrido[1,2-a]indole compound, and complete the preparation; The structural formula of the N-substituted indole compound in step I is as follows: In the formula, R 1 , R 2 , R 3 , R 4 , and R 5 are all H; Or R 1 , R 3 and R 5 one of which is CH 3 , and the rest are all H; or R 1 and R 4 one of them is COOCH 3 , and the rest are all H; Or R 2 is CN and the rest are all H; The Umemoto reagent in step I is a trifluoromethyl reagent, and the structural formula is as follows: During the photoirradiation reaction in step II, the wavelength of the blue light lamp is 440 - 460 nm; The structural formula of the pyrido[1,2-a]indole compound obtained in step IV is: wherein, R 1 , R 2 , R 3 , R 4 , and R 5 are all H; Or R 1 、R 3 and R 5 One of them is CH 3 , and the rest are all H; or R 1 and R 4 one of them is COOCH 3 , and the rest are all H; Or R 2 is CN, and the rest are all H.

2. The method for preparing a pyrido[1,2-a]indole compound according to claim 1, characterized in that the solvent in step I is dichloromethane.

3. The method for preparing a pyrido[1,2-a]indole compound according to claim 1, characterized in that the dosage ratio of the N-substituted indole compound to the solvent in step I is 0.28 - 0.32 mmol: 1 - 1.5 mL; the dosage ratio of the Umemoto reagent to the solvent is 0.08 - 0.12 mmol: 1 - 1.5 mL.

4. The method for preparing a pyrido[1,2-a]indole compound according to claim 3, characterized in that the dosage ratio of the N-substituted indole compound to the solvent in step I is 0.3 mmol: 1.5 mL; the dosage ratio of the Umemoto reagent to the solvent is 0.1 mmol: 1.5 mL.

5. The method for preparing a pyrido[1,2-a]indole compound according to claim 1, characterized in that during the photoirradiation reaction in step II, the irradiation time is 12 - 14 h.

6. The method for preparing a pyrido[1,2-a]indole compound according to claim 1, characterized in that step III uses a rotary evaporator for rotavaporization treatment.

7. The method for preparing a pyrido[1,2-a]indole compound according to claim 1, characterized in that for the column chromatography separation treatment in step IV, silica gel and a mobile phase are used, and the mobile phase is a mixture of petroleum ether and ethyl acetate.

8. The method for preparing a pyrido[1,2-a]indole compound according to claim 7, characterized in that petroleum ether and ethyl acetate are mixed in a volume ratio of 20:1.

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