A method for preparing 1-azafluorene and 1-azafluorene containing axial chirality

Abstract

The present invention discloses a method for synthesizing a 1-azafluorene compound and a 1-azafluorene compound containing a chiral axis at position 4. The specific method used in the present invention is to add a nickel catalyst, a ligand, an acetylenic nitrile compound and a Lewis acid additive to a solvent and stir, then add another acetylenic compound to the mixture, and after the reaction is completed, separate and purify to obtain a 1-azafluorene compound or a 1-azafluorene compound containing a chiral axis at position 4. The method realizes a one-step synthesis from an acetylenic nitrile compound and an alkyne to a 1-azafluorene skeleton, has the advantages of simple and safe operation, easy availability of raw materials, mild reaction conditions, high reaction efficiency and high enantioselectivity, and the prepared series of 1-azafluorene compounds can be widely used in the fields of organic chemical synthesis and medicinal chemistry.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic synthesis, and in particular relates to a 1-azafluorene compound and a preparation method of the 1-azafluorene containing axial chirality. Background Art

[0002] 1-Azafluorene ring is a bioisostere of fluorene. Due to its intramolecular pyridine structure, it is widely present in many bioactive molecules, which can bring good water solubility and biocompatibility [(a): Dininno F, Guthikonda R. Preparation of 2-(aza-9-flluorenonyl)carbapenem Antibacterial Agents: US5294610A[P]. 1994-03-15. (b): Hammblett C, Kattar S, Mampreian D, et al. Preparation of 6-(piperidin-1-yl)-Nicotinamide Derivatives for Treatment of Cancer: WO2007136605A2[P]. 2007-11-29. (c) Stamler J. Compositions Comprising Enzyme Inhibitors for Treating Tissue Injury:WO2020005938A1[P].2020-01-02.(d):Goel A,Sharma A,Umar S,et al.A new type of biocompatible fluorescent probeAFN for fixed and live cell imaging of intracellular lipid droplets[J].Analyst,2016,141(1):137-143.].With the development of synthetic chemistry, there are now many synthetic methods for 1-azafluorene compounds. However, these methods all have some shortcomings, such as the need to use precious metal catalysts or toxic oxidants, harsh reaction conditions, and low reaction efficiency. In addition, there is no report on the synthesis of chiral 1-azafluorene compounds [(a): Khan KM, Kianmehr E, Faghih N. Palladium-catalyzed regioselective benzylation-annulation of pyridine N-oxides with toluenederivatives via multiple CH bond activations: benzylation versus arylation [J]. Org. Lett., 2015, 17(3): 414-417. (b): Desrosiers JN, Wei X, Gutierrez O, et al. Nickel-Catalyzed C-3 Direct Arylation of Pyridinium Ions for the Synthesis of 1-Azafluorenes[J].Chem.Sci.,2016,7(8):5581-5586.(c):Scheerer JR,Angello NH,Wiley RE,et al.Synthesis and Spectrophotometric Analysis of 1-Azafluorenone Derivatives[J].Molecules,2020,25(15):3358-3366.(d):Scheerer JR,Angello NH,Wiley RE,et al.Domino Reaction Sequence for the Synthesis of[2.2.2]Diazabicycloalkenes and Base-Promoted Cycloreversion to 2-PyridoneAlkaloids[J].Org.Lett.,2018,20(17):5203-5207.].

[0003] Transition metal-catalyzed [2+2+2] cycloaddition reactions are an effective method for rapidly constructing 1-azafluorene rings from acetylene nitrile compounds and alkyne compounds. At present, there are only two reports on the synthesis of 1-azafluorene skeleton using this method, one by Louie's group using an iron catalytic system and the other by Liu Yuanhong's group using a nickel catalytic system [(a): Louie J, D'souza BR, Lane T K. Iron-catalyzed cycloaddition of alkynenitriles and alkynes[J]. Org.Lett., 2011, 13(11): 2936-2939. (b): Liu Y, You X, Xie X, et al. Nickel-Catalyzed[2+2+2]Cycloaddition ofAlkyne-Nitriles with Alkynes Assisted by Lewis Acids: Efficient Synthesis of Fused Pyridines[J]. Chem. Eur. J., 2016, 22(47): 16765-16769.]. However, the synthesis examples achieved in these studies are limited. Only three structures of 1-azafluorene compounds have been successfully synthesized, and the reaction yields are moderate, the regioselectivity is insufficient, and there are no examples of synthesizing 1-azafluorene structures containing axial chirality. Therefore, it is necessary to develop a method for synthesizing 1-azafluorene with high efficiency, high regioselectivity, and high enantioselectivity. Summary of the Invention

[0004] In response to the technical problems existing in the prior art, the purpose of the present invention is to provide a new method for synthesizing 1-azafluorene and 1-azafluorene compounds containing axial chirality using a transition metal-catalyzed [2+2+2] cycloaddition reaction under mild reaction conditions with high efficiency, high regioselectivity and high enantioselectivity.

[0005] A method for preparing 1-azafluorene comprises the following steps: stirring a nickel catalyst, a ligand, a Lewis acid, an acetylene nitrile compound and an acetylene compound in a solvent, and separating and purifying the mixture after the reaction to obtain the 1-azafluorene compound.

[0006] Preferably, the prepared 1-azafluorene compound III is prepared from an acetylene nitrile compound I and an acetylene compound II as raw materials, and can be represented by the following formula:

[0007]

[0008] The nickel catalyst is Ni(COD)2; the ligand is a phosphine ligand or a dinitrogen ligand, which is any one of PPh3, PCy3, dppe, dppp, dppb, BINAP, and dipy; the Lewis acid is ZnBr2; the solvent is any one of tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane, toluene, 1,2-dichloroethane, and acetonitrile; the reaction temperature during stirring in the solvent is 40 degrees Celsius, and the reaction time is 12 hours.

[0009] Preferably, the substituent R in the acetylene nitrile compound I, the acetylene compound II and the 1-azafluorene product III is 1 、R 2 、R 3 are all independent substituents, among which R 1 R is selected from alkyl, alkenyl or aryl; 2 Optionally selected from alkylaryl; R 3 Optionally selected from hydrogen, alkyl or aryl.

[0010] Preferably, the separation and purification includes suction filtration, column chromatography, and recrystallization.

[0011] Preferably, the column chromatography is based on 200-300 mesh silica gel, and the eluent is a mixture of two or more of petroleum ether, ethyl acetate, dichloromethane, toluene, and triethylamine.

[0012] A method for preparing 1-azafluorene containing axial chirality comprises the following steps: stirring a nickel catalyst, a chiral ligand, a Lewis acid, an acetylene nitrile compound and an acetylene compound in a solvent, and separating and purifying the mixture after the reaction to obtain the 1-azafluorene compound containing axial chirality.

[0013] Preferably, the prepared axial chirality-containing 1-azafluorene compound VI is prepared from an acetylene nitrile compound IV and an acetylene compound V as raw materials, and can be represented by the following equation:

[0014]

[0015] The nickel catalyst is Ni(COD)2; the chiral ligand is a chiral phosphine ligand, which is any one of BINAP, tol-BINAP, xyl-BINAP, 8H-BINAP, SegPhos, SynPhos, MeO-BIPHEP, BDPP, and DM-SegPhos; the Lewis acid is ZnBr2; the solvent is any one of tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane, toluene, 1,2-dichloroethane, and acetonitrile; and the reaction temperature during stirring in the solvent is 40 to 60 degrees Celsius.

[0016] Preferably, the substituent R in the acetylene nitrile compound IV, the acetylene compound V, and the product VI containing axial chirality 1-azafluorene is 4 、R 5 、R 6 are all independent substituents, among which R 4 Selected from alkyl, alkoxy and fluorine; R 5 、R 6 Optionally selected from alkyl groups.

[0017] Preferably, the separation and purification methods used include suction filtration, column chromatography, and recrystallization.

[0018] Preferably, the column chromatography is based on 200-300 mesh silica gel, and the eluent is a mixture of two or more of petroleum ether, ethyl acetate, dichloromethane, toluene, and triethylamine.

[0019] Compared with the prior art, the present invention has the following beneficial effects:

[0020] (1) The present invention provides a method for efficiently synthesizing 1-azafluorene and 1-azafluorene structures containing axial chirality

[0021] (2) The method of the present invention is simple and safe to operate, has mild reaction conditions, high reaction activity, high reaction efficiency, high atom economy, and good regioselectivity and enantioselectivity of the reaction.

[0022] (3) The use of non-precious metal catalysts is low-cost and can effectively avoid heavy metal residues in the synthetic products and the pollution of the reaction itself to the environment. DETAILED DESCRIPTION

[0023] The technical solution of the present invention is further described below by way of specific embodiments. It should be understood by those skilled in the art that the embodiments are merely to help understand the present invention and should not be regarded as specific limitations of the present invention.

[0024] The technical solutions provided by the present invention are as follows:

[0025] The present invention provides a method for constructing a 1-azafluorene structure by utilizing a nickel-catalyzed [2+2+2] cycloaddition reaction, comprising the following steps: (1) reacting raw materials I and II in a specific solvent under the action of a nickel catalyst, a ligand, and a Lewis acid; (2) adding a base after the reaction, stirring, and removing the Lewis acid by suction filtration; and (3) concentrating the solvent, separating and purifying by column chromatography, and obtaining a 1-azafluorene product III. The reaction equation is as follows:

[0026]

[0027] where R 1 、R 2 、R 3are all independent substituents, among which R 1 R is selected from alkyl, alkenyl or aryl; 2 Optionally selected from alkylaryl; R 3 Optionally selected from hydrogen, alkyl or aryl.

[0028] In step (1) of the preparation method, the nickel catalyst is Ni(COD)2, the ligand is a ligand having a structure represented by the following formulas A to G, the Lewis acid is ZnBr2, and the solvent is one of tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane, toluene, 1,2-dichloroethane, and acetonitrile. The reaction temperature is 40 degrees Celsius, and the reaction time is 12 hours.

[0029]

[0030] Preferably, the ligand is a structure shown in Formula E;

[0031] Preferably, the solvent is 1,4-dioxane.

[0032] The base used in step (2) of the preparation method is a mixture of ethyl acetate and triethylamine in a volume ratio of 1:1. The column chromatography used in step (3) of the preparation method is based on 200-300 mesh silica gel, and the eluent is a mixture of two or more of petroleum ether, ethyl acetate, dichloromethane, toluene, and triethylamine.

[0033] The present invention further provides a method for constructing an axially chiral 1-azafluorene structure by utilizing a nickel-catalyzed asymmetric [2+2+2] cycloaddition reaction, comprising the following steps: (1) reacting raw materials IV and V in a specific solvent under the action of a nickel catalyst, a chiral ligand, and a Lewis acid; (2) adding a base after the reaction, stirring, and removing the Lewis acid by suction filtration; and (3) concentrating the solvent, separating and purifying by column chromatography, and obtaining an axially chiral 1-azafluorene product VI. The reaction equation is as follows:

[0034]

[0035] where R 4 、R 5 、R 6 are all independent substituents, among which R 4 Selected from alkyl, alkoxy and fluorine; R 5 、R 6Optional from alkyl; the nickel catalyst in step (1) of the preparation method is Ni(COD)2, wherein the ligand is a ligand having a structure shown in the following formula H to formula P, wherein the Lewis acid is ZnBr2, and the solvent is one of tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane, toluene, 1,2-dichloroethane and acetonitrile. The reaction temperature is 40 to 60 degrees Celsius, and the reaction time is 12 hours.

[0036]

[0037] Preferably, the ligand is a structure represented by formula L;

[0038] Preferably, the solvent is tetrahydrofuran.

[0039] The base used in step (2) of the preparation method is a mixture of ethyl acetate and triethylamine in a volume ratio of 1:1. The column chromatography used in step (3) of the preparation method is based on 200-300 mesh silica gel, and the eluent is a mixture of two or more of petroleum ether, ethyl acetate, dichloromethane, toluene, and triethylamine.

[0040] The present invention is further explained and illustrated below with reference to the embodiments.

[0041] Example 1

[0042] Using 2-(2-(phenylethynyl)phenyl)acetonitrile 1a as the standard substrate, the reaction conditions for the synthesis of 1-azafluorene were studied:

[0043]

[0044]

[0045]

[0046] The values ​​in brackets are the separation yields, and condition 7 is the optimal reaction condition.

[0047] Example 2

[0048] Using 2-(2-(phenylethynyl)phenyl)acetonitrile 1a as a standard substrate, the ligands used in the synthesis of 1-azafluorene compounds involving terminal alkynes were studied:

[0049]

[0050]

[0051] Where rr is the product regioselectivity, and condition 5 is the optimal.

[0052] Example 3

[0053] Using 2-(2-(phenylethynyl)phenyl)acetonitrile 1a as the standard substrate, the substrate ratios and additives used in the synthesis of 1-azafluorene compounds involving terminal alkynes were studied:

[0054]

[0055]

[0056]

[0057] In both conditions 3 and 4, 1 mg / μmol MS was used as an additive, where rr is the product regioselectivity and the values ​​in brackets are the separation yields, with condition 4 being the optimal.

[0058] Example 4

[0059] Using 2-(2-(2-methoxyphenyl)ethynyl)phenyl)acetonitrile 1aa as a standard substrate, the solvents used in the synthesis of axially chiral 1-azafluorene compounds were studied:

[0060]

[0061]

[0062] Where er is the product enantioselectivity ratio, and condition 2 is the optimal.

[0063] Example 5

[0064] Using 2-(2-(2-methoxyphenyl)ethynyl)phenyl)acetonitrile 1aa as a standard substrate, the chiral ligands used in the synthesis of axially chiral 1-azafluorene compounds were studied:

[0065]

[0066]

[0067]

[0068] Where er is the product enantioselectivity ratio, and the separation yield is in brackets, with condition 5 being the optimal.

[0069] Example 6

[0070] The preparation method involves the following steps: In an argon-filled glove box, a dry, sealed 4 mL reaction vial containing a magnetic stirrer was charged with reactant I (0.2 mmol, 1.0 equiv), Ni(COD)2 (0.02 mmol, 10 mol%), dppp (0.03 mmol, 15 mol%), and ZnBr2 (0.2 mmol, 1.0 equiv). 1,4-dioxane (2000 μL, 0.1 M) was then added via pipette. After stirring at room temperature for 2 minutes, the acetylene compound II (0.3 mmol, 1.5 equiv) was added via pipette. The reaction was sealed and placed on a metal heating block at 40°C for 12 hours. After complete reaction by TLC, 0.4 mL of ethyl acetate and 0.4 mL of triethylamine were added. After stirring for 5 minutes, a solid precipitated. The insoluble material was removed by filtration through a celite-silica gel layer and washed with ethyl acetate (5 mL x 5). The solvent was removed under reduced pressure, and column chromatography was performed using 200-300 mesh silica gel with one or a mixture of petroleum ether, ethyl acetate, dichloromethane, toluene, and triethylamine as the mobile phase to obtain 1-azafluorene product III.

[0071] Example 7

[0072] In an argon atmosphere glove box, reactants I (0.2 mmol, 1.0 equiv), Ni(COD)2 (0.02 mmol, 10 mol%), BINAP (0.03 mmol, 15 mol%), ZnBr2 (0.2 mmol, 1.0 equiv), MS (200 mg, 1 mg / μmol) was added with 1,4-dioxane (2000 μL, 0.1 M) using a pipette. After the addition was completed, the acetylene compound II (0.6 mmol, 3.0 equiv) was added using a pipette and the mixture was sealed and placed in a metal heating block at 40°C for 12 h. After the reaction of the raw materials by TLC was complete, 0.4 mL of ethyl acetate and 0.4 mL of triethylamine were added and stirred for 5 min to precipitate a solid. The insoluble matter was removed by filtration using a diatomaceous earth-silica gel layer and washed with ethyl acetate (5 mL x 5). The solvent was removed under reduced pressure and a mixture of petroleum ether, ethyl acetate, dichloromethane, toluene and triethylamine was used as the mobile phase and column chromatography was performed using 200-300 mesh silica gel to obtain the 1-azafluorene product III. The rr value of the product was determined by the separation yield combined with the crude 1 Confirmed by HNMR.

[0073] Example 8

[0074] The preparation method involves the following steps: In an argon-filled glove box, reactants IV (0.1 mmol, 1.0 equiv), Ni(COD)2 (0.01 mmol, 10 mol%), (R)-SegPhos (0.015 mmol, 15 mol%), and ZnBr2 (0.1 mmol, 1.0 equiv) were added to a dry, sealed 4 mL reaction vial with a magnetic stirrer. THF (1000 μL, 0.1 M) was then added via pipette. After stirring at room temperature for 2 minutes, the acetylene compound V (0.15 mmol, 1.5 equiv) was added via pipette. The reaction was sealed and placed on a metal heating block at 40°C for 12 hours. After complete reaction of the starting materials by TLC, 0.2 mL of ethyl acetate and 0.2 mL of triethylamine were added. After stirring for 5 minutes, a solid precipitated. The insoluble material was removed by filtration through a celite-silica gel layer and washed with ethyl acetate (5 mL x 3). The solvent was removed under reduced pressure, and column chromatography was performed using 200-300 mesh silica gel with one or a mixture of petroleum ether, ethyl acetate, dichloromethane, toluene, and triethylamine as the mobile phase to obtain 1-azafluorene product VI. The er value of the product was determined by high performance liquid chromatography equipped with a chiral separation column.

[0075] Example 9

[0076] In this example, 2,3-dipentyl-4-phenyl-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0077]

[0078] Colorless oil (75.7 mg, 99% yield) 1 H NMR(400MHz, CDCl3)δ=7.58–7.44(m,4H),7.34–7.22(m,2H),7.22–7.14(m,1H),7.08–6.90(m,1H),6.22(d,J=7.8,1H),4.00(s,2H),2 .96–2.88(m,2H),2.49–2.42(m,2H),1.86–1.75(m,2H),1.49–1.35(m,6H),1.20–1.11(m,4H),0.93(t,J=7.0,3H),0.81–0.76(m,3H). 13C NMR (101MHz, CDCl3) δ = 161.2, 159.0, 144.5, 141.7, 140.2, 138.3, 131.9, 130.9, 129.0, 128.5, 128.0, 126. 63,126.60,125.0,122.6,38.6,35.9,32.5,32.2,30.9,30.6,29.0,22.8,22.2,14.3,14.0.HRMS(ESI)m / z calc'dfor C 28 H 34 N(M+H) + :384.2686,found:384.2682.

[0079] Example 10

[0080] In this example, 2,3-diethyl-4-phenyl-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0081]

[0082] White solid (62.0 mg, 98% yield) 1 H NMR(400MHz, CDCl3)δ=7.58–7.47(m,4H),7.31–7.27(m,2H),7.21–7.15(m,1H),7.01–6.94(m,1H),6.20(d ,J=7.8,1H),3.99(s,2H),2.97(q,J=7.5,2H),2.54(q,J=7.5,2H),1.40(t,J=7.5,3H),1.03(t,J=7.5,3H). 13 C NMR(101MHz, CDCl3)δ=161.3,159.8,144.5,141.7,140.1,138.3,132.9,131.1,129 .1,128.5,128.0,126.7,125.0,122.6,38.6,28.7,22.1,15.7,14.9.HRMS(ESI)m / z calc'd forC 22 H 22 N(M+H) + :300.1747,found:300.1745.

[0083] Example 11

[0084] In this example, 2,3-diethyl-4-phenyl-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0085]

[0086] White solid (52.8 mg, 96% yield) 1 H NMR(400MHz, CDCl3)δ=7.58–7.48(m,4H),7.29–7.24(m,2H),7.24–7.17(m,1H) ,7.03–6.97(m,1H),6.36(d,J=7.8,1H),3.98(s,2H),2.65(s,3H),2.07(s,3H). 13 C NMR(101MHz, CDCl3)δ=161.0,155.2,144.3,141.7,140.1,138.4,130.9,129.2,1 28.4,128.0,127.6,126.6,125.0,122.6,38.6,23.7,15.9.HRMS(ESI)m / zcalc'd for C 20 H 18 N(M+H) + :272.1434,found:272.1435.

[0087] Example 12

[0088] In this example, 2,3,4-triphenyl-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0089]

[0090] White solid (83.3 mg, 99% yield) 1 H NMR(400MHz, CDCl3)δ=7.58(d,J=7.6,1H),7.38–7.34(m,2H),7.33–7.28(m,3H),7.28–7.23(m, 1H),7.22–7.12(m,5H),7.09–6.97(m,4H),6.95–6.88(m,2H),6.54(d,J=7.8,1H),4.18(s,2H). 13C NMR (101MHz, CDCl3) δ = 163.6, 155.9, 144.6, 142.2, 141.1, 139.6, 138.0, 137.6, 134.0, 131.8, 131.6, 13 0.1,129.3,128.5,127.8,127.7,127.5,127.4,127.3,126.9,126.4,125.1,123.3,39.1.HRMS(ESI)m / z calc'd for C 30 H 22 N(M+H) + :396.1747,found:396.1754.

[0091] Example 13

[0092] In this example, 2,3-diethyl-4-(p-tolyl)-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0093]

[0094] White solid (69.6 mg, 98% yield) 1 H NMR(400MHz, CDCl3)δ=7.50(d,J=7.5,1H),7.34(d,J=7.7,2H),7.21–7.14(m,3H),7.04–6.96(m,1H),6.28(d,J=7 .8,1H),3.98(s,2H),2.96(q,J=7.5,2H),2.58–2.47(m,2H),2.51(s,3H),1.40(t,J=7.5,3H),1.03(t,J=7.5,3H). 13 C NMR (101MHz, CDCl3) δ=161.3,159.7,144.6,141.7,140.3,137.6,135.2,133.1,131.2,129 .7,128.3,126.61,126.55,124.9,122.7,38.6,28.7,22.0,21.6,15.7,14.8.HRMS(ESI)m / z calc'd for C 23 H 24 N(M+H) + :314.1903,found:314.1905.

[0095] Example 14

[0096] In this example, 2,3-diethyl-4-(4-methoxyphenyl)-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0097]

[0098] Yellow solid (75.7 mg, 98% yield) 1 H NMR (400MHz, CDCl3) δ=7.55–7.46(m,1H),7.23–7.15(m,3H),7.12–7.05(m,2H),7.04–6.98(m,1H),6.33(d,J=7.8 ,1H),3.98(s,2H),3.94(s,3H),2.97(q,J=7.5,2H),2.55(q,J=7.5,2H),1.40(t,J=7.5,3H),1.03(t,J=7.5,3H). 13 C NMR (101MHz, CDCl3) δ=161.2,159.6,159.2,144.1,141.6,140.2,133.3,131.3,130.3,129 .5,126.54,126.47,124.8,122.6,114.3,55.3,38.5,28.6,21.9,15.5,14.7.HRMS(ESI)m / z calc'd for C 23 H 24 NO(M+H) + :330.1852,found:330.1843.

[0099] Example 15

[0100] In this example, 2,3-diethyl-4-(4-fluorophenyl)-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0101]

[0102] White solid (70.3 mg, 98% yield) 1H NMR(400MHz, CDCl3)δ=7.50(d,J=7.5,1H),7.29–7.22(m,4H),7.22–7.15(m,1H),7.06–6.96(m,1H),6.25(d ,J=7.8,1H),3.97(s,2H),2.96(q,J=7.5,2H),2.52(q,J=7.5,2H),1.40(t,J=7.6,3H),1.02(t,J=7.5,3H). 13 CNMR(101MHz, CDCl3)δ=162.6(d,J=247.0),161.4,159.9,143.2,141.7,139.9,134.2(d,J=3.6),133.0, 131.1,130.2(d,J=7.9),126.75,126.68,125.1,122.5,116.2(d,J=21.4),38.6,28.7,22.0,15.6,14.8. 19 F NMR(376MHz, CDCl3)δ=-112.0–-116.0(m).HRMS(ESI)m / z calc'd for C 22 H 21 FN(M+H) + :318.1653,found:318.1679.

[0103] Example 16

[0104] In this example, 4-(4-chlorophenyl)-2,3-diethyl-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0105]

[0106] Colorless oil (40.5 mg, 61% yield) 1 H NMR (400MHz, CDCl3) δ=7.65–7.46(m,3H),7.34–7.13(m,3H),7.09–6.97(m,1H),6.29(d,J=7.8,1 H),3.98(s,2H),2.96(q,J=7.5,2H),2.51(q,J=7.5,2H),1.39(t,J=7.5,3H),1.02(t,J=7.5,3H). 13C NMR(101MHz, CDCl3)δ=161.5,159.9,143.0,141.7,139.8,136.7,134.1,132.8,130.8, 130.0,129.4,126.8,126.7,125.1,122.5,38.6,28.7,22.0,15.6,14.8.HRMS(ESI)m / z calc'd for C 22 H 21 ClN(M+H) + :334.1357,found:334.1357.

[0107] Example 17

[0108] In this example, 2,3-diethyl-4-(4-trifluoromethyl)phenyl)-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0109]

[0110] White solid (70.6 mg, 93% yield) 1 H NMR(400MHz, CDCl3)δ=7.82(d,J=8.0,2H),7.52(d,J=7.5,1H),7.45(d,J=7.9,2H),7.25–7.13(m,1H),7.06–6.91(m,1 H), 6.17 (d, J = 7.8, 1H), 3.99 (s, 2H), 2.98 (q, J = 7.5, 2H), 2.50 (q, J = 7.5, 2H), 1.41 (t, J = 7.5, 3H), 1.02 (t, J = 7.5, 3H). 13 CNMR(101MHz, CDCl3)δ=161.6,160.0,142.6,142.2,141.8,139.6,132.4,130.5,130.4(q,J=32.5),1 29.1,126.9,126.8,126.1(q,J=3.8),125.2,124.3(q,J=272.2),122.3,38.6,28.6,22.0,15.6,14.7. 19 FNMR(376MHz, CDCl3)δ=-62.3.HRMS(ESI)m / z calc'd for C 23 H 21 F3N(M+H) +:368.1621,found:368.1620.

[0111] Example 18

[0112] In this example, 1-(4-(2,3-diethyl-9H-indeno[2,1-b]pyridin-4-yl)phenyl)ethan-1-one was prepared, and its structural formula is as follows:

[0113]

[0114] White solid (64.8 mg, 96% yield) 1 H NMR (400MHz, CDCl3) δ = 8.15 (d, J = 8.2, 2H), 7.52 (d, J = 7.5, 1H), 7.43 (d, J = 8.0, 2H), 7.24–7.15 (m, 1H), 7.05–6.95 (m, 1H), 6. 20(d,J=7.8,1H),3.99(s,2H),2.97(q,J=7.5,2H),2.73(s,3H),2.50(q,J=7.5,2H),1.40(t,J=7.5,3H),1.02(t,J=7.5,3H). 13 C NMR(101MHz, CDCl3)δ=197.9,161.5,159.9,143.5,143.1,141.8,139.6,136.8,132.4,130.5,12 9.1,129.0,126.9,126.8,125.1,122.4,38.6,28.6,26.9,22.1,15.6,14.8.HRMS(ESI)m / zcalc'd for C 24 H 24 NO(M+H) + :342.1852,found:342.1851.

[0115] Example 19

[0116] In this example, methyl 4-(2,3-diethyl-9H-indeno[2,1-b]pyridin-4-yl)benzoate was prepared, and its structural formula is as follows:

[0117]

[0118] White solid (76.4 mg, 99% yield) 1 H NMR (400MHz, CDCl3) δ = 8.23 ​​(d, J = 8.2, 2H), 7.51 (d, J = 7.5, 1H), 7.40 (d, J = 8.2, 2H), 7.23–7.17 (m, 1H), 7.02–6.93 (m, 1H), 6. 19(d,J=7.8,1H),4.01(s,3H),3.99(s,2H),2.97(q,J=7.5,2H),2.50(q,J=7.5,2H),1.40(t,J=7.5,3H),1.01(t,J=7.5,3H). 13 C NMR(101MHz, CDCl3)δ=167.0,161.5,159.9,143.3,143.2,141.8,139.7,132.4,130.5,130.4,13 0.0,128.8,126.9,126.8,125.1,122.5,52.5,38.6,28.6,22.1,15.6,14.8.HRMS(ESI)m / zcalc'd for C 24 H 24 NO2(M+H) + :358.1802,found:358.1798.

[0119] Example 20

[0120] In this example, 2,3-diethyl-4-naphthalen-2-yl-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0121]

[0122] Colorless oil (66.9 mg, 94% yield) 1H NMR (400MHz, CDCl3) δ = 8.02 (dd, J = 15.9, 8.0, 2H), 7.93–7.85 (m, 1H), 7.80 (s, 1 H),7.65–7.55(m,2H),7.51(d,J=7.5,1H),7.43(d,J=8.3,1H),7.16(t,J=7.5, 1H),6.87(t,J=7.6,1H),6.20(d,J=7.8,1H),4.03(s,2H),3.01(q,J=7.2,2H), 2.66–2.57(m,1H),2.57–2.47(m,1H),1.44(t,J=7.5,2H),1.04(t,J=7.4,5H). 13 C NMR(101MHz, CDCl3)δ=161.4,159.9,144.2,141.7,140.1,135.7,133.6,133.0,132.9,131.0,128.9,128.3,1 28.1,127.2,126.8,126.7,126.63,126.61,126.5,125.0,122.7,38.6,28.7,22.1,15.7,14.8.HRMS(ESI)m / z calc'd for C 26 H 24 N(M+H) + :350.1903,found:350.1905.

[0123] Example 21

[0124] In this example, 4-(dibenzo[b,d]furan-2-yl)-2,3-diethyl-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0125]

[0126] White solid (67.6 mg, 87% yield) 1H NMR (400MHz, CDCl3) δ=7.98–7.88(m,2H),7.76(d,J=8.4,1H),7.67(d,J=8.3,1H),7.57–7.47(m,2H),7.44–7.33(m,2H),7.20–7.09(m,1 H),6.98–6.85(m,1H),6.20(d,J=7.8,1H),4.04(s,2H),3.02(q,J=7.5,2H),2.66–2.54(m,2H),1.45(t,J=7.5,3H),1.06(t,J=7.5,3H). 13 C NMR (101MHz, CDCl3)δ=161.4,159.9,156.8,155.8,144.2,141.7,140.1,133.3,132.8,131.4,127.7,127.6,126.68,1 26.65,125.03,124.99,124.1,123.0,122.6,121.0,120.5,112.4,112.0,38.6,28.7,22.1,15.7,14.8.HRMS(ESI)m / z calc'd for C 28 H 24 NO(M+H) + :390.1852,found:390.1854.

[0127] Example 22

[0128] In this example, 2,3-diethyl-4-(6-methoxypyridin-2-yl)-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0129]

[0130] Green solid (58.8 mg, 83% yield) 1H NMR (400MHz, CDCl3) δ=7.77–7.69(m,1H),7.51(d,J=7.5,1H),7.24–7.15(m,1H),7.08–6.99(m,1H),6.94(d,J=7.2,1H),6.89(d,J=8.3,1H),6. 28(d,J=7.8,1H),3.99(s,2H),3.90(s,3H),2.97(q,J=7.5,2H),2.65–2 .55(m,1H),2.55–2.45(m,1H),1.40(t,J=7.5,3H),1.12(t,J=7.5,3H). 13 C NMR(101MHz, CDCl3)δ=164.4,161.7,160.0,154.7,142.5,141.8,139.6,139.2,132.6,130.7,12 6.8,126.7,125.0,122.4,116.9,110.2,53.8,38.7,28.5,22.3,15.8,14.8.HRMS(ESI)m / zcalc'd for C 22 H 23 N2O(M+H) + :331.1805,found:331.1801.

[0131] Example 23

[0132] In this example, 2,3-diethyl-4-thiophen-2-yl-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0133]

[0134] White solid (64.3 mg, 98% yield) 1 H NMR (400MHz, CDCl3) δ = 7.55 (dd, J = 5.1, 1.2, 1H), 7.52 (d, J = 7.5, 1H), 7.29–7.22 (m, 2H), 7.13–7.06 (m, 1H), 7.05–6.98 ( m,1H),6.38(d,J=7.8,1H),4.01(s,2H),2.99(q,J=7.6,2H),2.77–2.56(m,2H),1.41(t,J=7.6,3H),1.14(t,J=7.5,3H). 13C NMR(101MHz, CDCl3)δ=161.1,159.5,141.7,139.6,137.9,137.0,135.2,133.0,127.8,1 27.1,126.90,126.88,126.5,125.0,122.6,38.5,28.5,22.3,16.3,14.8.HRMS(ESI)m / z calc'd for C 20 H 20 NS(M+H) + :306.1311,found:306.1311.

[0135] Example 24

[0136] In this example, 2,3-diethyl-4-(2-methylprop-1-yl)-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0137]

[0138] Colorless oil (58.1 mg, 97% yield) 1 H NMR(400MHz, CDCl3)δ=7.81–7.76(m,1H),7.55–7.51(m,1H),7.33–7.24(m,2H),6.39–6.35(m,1H),4.07–3.82(m,2H),2 .92(q,J=7.5,2H),2.77–2.61(m,2H),2.05(d,J=1.5,3H),1.45(d,J=1.2,3H),1.35(t,J=7.6,3H),1.10(t,J=7.5,3H). 13 C NMR(101MHz, CDCl3)δ=161.4,159.2,141.7,141.0,140.8,137.7,133.5,131.0,126.8 ,126.5,124.9,122.7,120.6,38.6,28.7,25.4,22.1,19.5,14.8,14.7.HRMS(ESI)m / z calc'd for C 20 H 24 N(M+H) + :278.1903,found:278.1903.

[0139] Example 25

[0140] In this example, 2,3-diethyl-4-hexyl-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0141]

[0142] Colorless oil (52.2 mg, 86% yield) 1 H NMR(400MHz, CDCl3)δ=7.77(d,J=7.8,1H),7.57(d,J=7.4,1H),7.43–7.35(m,1H),7.34–7.28(m,1H),3.93(s,2H),3.05–2.98(m,2H),2 .91(q,J=7.6,2H),2.78(q,J=7.5,2H),1.72–1.62(m,2H),1.62–1.53(m,2H),1.45–1.29(m,7H),1.23(t,J=7.5,3H),0.96–0.90(m,3H). 13 C NMR (101MHz, CDCl3) δ = 161.6, 159.6, 145.0, 141.9, 140.5, 132.7, 131.1, 127.0, 126.4, 125. 2,122.9,38.8,31.8,30.1,29.45,29.43,29.0,22.7,21.1,15.8,14.9,14.2.HRMS(ESI)m / z calc'd for C 22 H 30 N(M+H) + :308.2373,found:308.2373.

[0143] Example 26

[0144] In this example, 2,3-diethyl-6,7-dimethoxy-4-phenyl-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0145]

[0146] White solid (63.9 mg, 89% yield) 1H NMR(400MHz, CDCl3)δ=7.58–7.50(m,2H),7.50–7.42(m,1H),7.33–7.29(m,2H),7.03(s,1H),5.69(s,1H),3.88(s ,2H),3.86(s,3H),3.38(s,3H),2.94(q,J=7.5,2H),2.55(q,J=7.5,2H),1.38(t,J=7.5,3H),1.03(t,J=7.5,3H). 13 C NMR(101MHz, CDCl3)δ=161.4,158.2,148.4,147.9,142.8,138.3,134.2,132.5,132.4,13 1.4,128.9,127.8,108.0,105.6,56.1,55.3,38.4,28.5,22.0,15.7,14.9.HRMS(ESI)m / z calc'd for C 24 H 26 NO2(M+H) + :360.1958,found:360.1959.

[0147] Example 27

[0148] In this example, 4-(2,3-diethyl-9H-indeno[2,1-b]pyridin-4-yl)-N,N-diphenylaniline was prepared, and its structural formula is as follows:

[0149]

[0150] Yellow solid (78.2 mg, 85% yield) 1 H NMR (400MHz, CDCl3) δ = 7.53 (d, J = 7.4, 1H), 7.37–7.30 (m, 4H), 7.28–7.21 (m, 7H), 7.19–7.12 (m, 2H), 7.12–7.06 (m, 3H) ), 6.51 (d, J = 7.8, 1H), 4.00 (s, 2H), 2.99 (q, J = 7.5, 2H), 2.65 (q, J = 7.4, 2H), 1.42 (t, J = 7.5, 3H), 1.10 (t, J = 7.4, 3H). 13CNMR(101MHz, CDCl3)δ=161.3,159.8,147.8,147.5,144.3,141.8,140.3,133.2,132.0,131.4,129.5 ,129.4,126.6,126.5,125.0,124.7,123.8,123.3,122.7,38.6,28.7,22.1,15.8,14.9.HRMS(ESI)m / z calc'd for C 34 H 31 N2(M+H) + :467.2482,found:467.2478.

[0151] Example 28

[0152] In this example, 4-(4-(9H-carbazol-9-yl)phenyl)-2,3-diethyl-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0153]

[0154] Yellow solid (82.9 mg, 88% yield) 1 H NMR(400MHz, CDCl3)δ=8.21(d,J=7.7,2H),7.78(d,J=8.0,2H),7.64–7.46(m,6H),7.40–7.32(m,2H),7.29–7.22(m,2H),7.14– 7.07(m,1H),6.42(d,J=7.8,1H),4.05(s,2H),3.04(q,J=7.5,2H),2.70(q,J=7.5,2H),1.46(t,J=7.5,3H),1.16(t,J=7.5,3H). 13 C NMR (101MHz, CDCl3)δ=161.5,160.0,143.5,141.9,140.9,140.0,137.5,132.8,131.2,130.2,127.6,126 .9,126.8,126.2,125.2,123.7,122.4,120.6,120.3,109.8,38.7,28.7,22.3,15.8,14.9.HRMS(ESI)m / z calc'd forC 34 H 29 N2(M+H) +:465.2325,found:465.2330.

[0155] Example 29

[0156] In this example, 2,3-diethyl-4-(9-phenyl-9H-carbazol-3-yl)-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0157]

[0158] Yellow solid (75.4 mg, 81% yield) 1 H NMR(400MHz, CDCl3)δ=8.11(d,J=7.7,1H),8.07(d,J=1.6,1H),7.77–7.6 3(m,4H),7.60(d,J=8.4,1H),7.57–7.40(m,4H),7.36–7.28(m,2H),7.24 –7.08(m,1H),6.96–6.80(m,1H),6.27(d,J=7.8,1H),4.03(s,2H),3.02( q,J=7.5,2H),2.71–2.55(m,2H),1.45(t,J=7.5,3H),1.07(t,J=7.4,3H). 13 C NMR(101MHz, CDCl3)δ=161.28,159.79,145.16,141.69,141.39,140.47,1 40.41,137.72,133.69,131.64,130.11,129.80,127.76,127.23,126.70,1 26.54,126.48,126.44,124.91,123.88,123.40,122.88,120.63,120.30, 120.10,110.39,110.20,38.69,28.79,22.10,15.78,14.91.HRMS(ESI)m / z calc'd for C 34 H 29 N2(M+H) + :465.2325,found:465.2322.

[0159] Example 30

[0160] In this example, 2-methyl-3,4-diphenyl-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0161]

[0162] White solid (32.7 mg, 47% yield) 1 H NMR(400MHz, CDCl3)δ=7.55(d,J=7.5,1H),7.30–7.24(m,3H),7.24–7.18(m,3H),7.18–7.14 (m,1H),7.11–7.07(m,2H),7.07–6.98(m,3H),6.47(d,J=7.8,1H),4.08(s,2H),2.45(s,3H). 13 C NMR (101MHz, CDCl3) δ = 162.8, 154.3, 144.1, 141.6, 139.7, 138.3, 137.4, 134.8, 130.8, 130. 2,129.0,128.4,128.0,127.6,127.0,126.9,126.8,125.1,122.9,38.8,24.1.HRMS(ESI)m / z calc'd for C 25 H 20 N(M+H) + :334.1590,found:334.1586.

[0163] Example 31

[0164] In this example, 3-methyl-2,4-diphenyl-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0165]

[0166] White solid (35.0 mg, 51% yield) 1H NMR (400MHz, CDCl3) δ=7.65–7.55(m,5H),7.55–7.52(m,1H),7.51–7.46(m,2H),7.45–7.39(m,1H),7.37– 7.32(m,2H),7.29–7.18(m,1H),7.04(td,J=7.6,1.1,1H),6.43(d,J=7.8,1H),4.11(s,2H),2.11(s,3H). 13 C NMR (101MHz, CDCl3) δ=161.5,156.8,145.5,142.2,141.2,139.6,138.3,131.9,129.4,12 9.43,128.42,128.3,128.0,127.5,127.2,126.8,125.1,123.1,38.7,17.5.HRMS(ESI)m / z calc'd forC 25 H 20 N(M+H) + :334.1590,found:334.1589.

[0167] Example 32

[0168] In this example, 3-hexyl-4-phenyl-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0169]

[0170] Colorless oil (65.0 mg, 98% yield) 1 H NMR(400MHz, CDCl3)δ=8.41(s,1H),7.59–7.48(m,4H),7.34–7.27(m,2H),7.24–7.19(m,1H),7.05–6.98(m,1H) ,6.39(d,J=7.8,1H),4.00(s,2H),2.51–2.44(m,2H),1.51–1.38(m,2H),1.28–1.09(m,6H),0.82(t,J=6.8,3H). 13C NMR(101MHz, CDCl3)δ=162.2,148.3,143.8,142.0,139.8,137.4,134.5,132.8,129.1,128.5, 128.2,127.1,126.7,125.1,123.2,38.5,31.52,31.49,30.2,29.1,22.6,14.1.HRMS(ESI)m / z calc'd for C 24 H 26 N(M+H) + :328.2060,found:328.2059.

[0171] Example 33

[0172] In this example, 3-cyclopropyl-4-phenyl-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0173]

[0174] Colorless oil (44.7 mg, 79% yield) 1 H NMR(400MHz, CDCl3)δ=8.15(s,1H),7.61–7.46(m,4H),7.40–7.32(m,2H),7.28–7.19(m,1H) ,7.10–6.96(m,1H),6.48(d,J=7.8,1H),4.00(s,2H),1.75–1.58(m,1H),0.83–0.71(m,4H). 13 C NMR(101MHz, CDCl3)δ=162.1,144.9,144.3,142.1,139.6,137.5,134.9,132.3, 129.1,128.7,128.1,127.2,126.7,125.1,123.3,38.4,11.6,8.5.HRMS(ESI)m / z calc'd for C 21 H 18 N(M+H) + :284.1434,found:284.1429.

[0175] Example 34

[0176] In this example, 4-phenyl-3-(trimethylsilyl)-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0177]

[0178] Colorless oil (47.0 mg, 75% yield) 1 H NMR (400MHz, CDCl3) δ = 8.63 (s, 1H), 7.56–7.50 (m, 4H), 7.33–7.27 (m, 2H), 7.25 –7.19(m,1H),7.05–6.96(m,1H),6.32(d,J=7.8,1H),4.04(s,2H),0.05(s,9H). 13 C NMR(101MHz, CDCl3)δ=165.4,152.3,150.5,141.4,139.7,139.6,132.6,131.4,1 28.9,128.7,128.4,127.2,126.8,125.0,123.5,38.8,0.6..HRMS(ESI)m / zcalc'd for C 21 H 22 NSi(M+H) + :316.1516,found:316.1516.

[0179] Example 35

[0180] In this example, 3,4-diphenyl-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0181]

[0182] White solid (43.7 mg, 68% yield) 1 H NMR (400MHz, CDCl3) δ = 8.52 (s, 1H), 7.54 (d, J = 7.5, 1H), 7.39–7.31 (m, 3H), 7.23 (t, J = 3.8, 1H), 7.19 (d q,J=4.9,2.7,2.2,5H),7.12(dd,J=7.2,2.6,2H),7.03(t,J=7.6,1H),6.61(d,J=7.9,1H),4.07(s,2H). 13C NMR(101MHz, CDCl3)δ=163.9,148.2,142.9,142.1,139.6,137.8,137.0,135.4,132.8,130 .2,129.4,128.7,128.04,127.97,127.4,127.0,126.8,125.1,123.6,38.7.HRMS(ESI)m / z calc'dfor C 24 H 18 N(M+H) + :320.1434,found:320.1432.

[0183] Example 36

[0184] In this example, 3-(2-(benzyloxy)ethyl)-4-phenyl-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0185]

[0186] Colorless oil (38.7 mg, 50% yield) 1 H NMR(400MHz, CDCl3)δ=8.52(s,1H),7.63–7.50(m,4H),7.36–7.30(m,2H),7.30–7.23(m,6H),7.12– 6.97(m,1H),6.40(d,J=7.8,1H),4.44(s,2H),4.05(s,2H),3.56(t,J=7.1,2H),2.86(t,J=7.1,2H). 13 C NMR (101MHz, CDCl3) δ=162.7,148.6,144.3,142.0,139.6,138.3,137.0,132.9,130.6,129.2,1 28.5,128.3,127.68,127.66,127.2,126.8,125.1,123.2,72.9,70.4,38.5,30.7.HRMS(ESI)m / z calc'dfor C 27 H 24 NO(M+H) + :378.1849,found:378.1852.

[0187] Example 37

[0188] In this example, (R)-2,3-diethyl-4-(2-methoxyphenyl)-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0189]

[0190] Colorless oil (33.9 mg, 97% yield) 98.5:1.5er. 1 H NMR (400MHz, CDCl3) δ=7.54–7.45(m,2H),7.21–7.07(m,4H),7.05–6.94(m,1H),6.30(d,J=7.8,1H),3.98(s,2H) ,3.67(s,3H),2.98(q,J=7.5,2H),2.64–2.53(m,1H),2.53–2.41(m,1H),1.41(t,J=7.5,3H),1.01(t,J=7.5,3H). 13 CNMR(101MHz, CDCl3)δ=161.3,159.6,156.6,141.7,141.1,140.4,133.4,131.3,130.2,129. 7,126.8,126.7,126.4,124.9,122.1,121.2,111.3,55.6,38.6,28.7,22.3,15.0,14.8.HPLC conditions: [Daicel CHIRALPAC AD-H (4.6mmΦ×250mm L, Particle Size: 5μm); hexane / 2-propanol=93 / 7; flow rate=1.0mL / min; detectionwavelength=270nm; t R =6.52(major),5.79(minor)min.[α] D 27 ℃=-58.42(c 0.93,CHCl3).HRMS(ESI)m / z calc'd for C 23 H 24 NO(M+H) + :330.1852,found:330.1865.

[0191] Example 38

[0192] In this example, (R)-4-(2-ethoxyphenyl)-2,3-diethyl-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0193]

[0194] Colorless oil (32.3 mg, 94% yield) 98.5:1.5er. 1 H NMR (400MHz, CDCl3) δ=7.58–7.43(m,2H),7.21–7.03(m,4H),7.04–6.94(m,1H),6.33(d,J=7.8,1H),3.98(s,1H),4.04–3.89( m,3H),2.97(q,J=7.5,2H),2.64–2.53(m,1H),2.53–2.42(m,1H),1.40(t,J=7.5,3H),1.07(t,J=7.0,3H),1.01(t,J=7.5,3H). 13 C NMR(101MHz, CDCl3)δ=161.2,159.5,155.9,141.7,141.4,140.5,133.5,131.4,130.3,129.6,1 27.1,126.6,126.4,124.8,122.2,121.0,112.4,63.8,38.6,28.7,22.3,15.0,14.8,14.7.HPLC conditions: [DaicelCHIRALPAKAD-H (4.6mmΦ×250mm L, Particle Size: 5μm); hexane / 2-propanol=95 / 5; flow rate=1.0mL / min; detection wavelength=277nm; t R =5.11(major),6.10(minor)min.[α] D 27 ℃=-91.74(c 0.71,CHCl3).HRMS(ESI)m / z calc'd for C 24 H 26 NO(M+H) + :344.2009,found:344.2017.

[0195] Example 39

[0196] In this example, (R)-2,3-diethyl-4-(2-isopropylphenyl)-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0197]

[0198] Colorless oil (25.1 mg, 70% yield) 98.5:1.5er. 1 H NMR (400MHz, CDCl3) δ = 7.49 (d, J = 7.6, 1H), 7.17 (t, J = 7.5, 1H), 7.13 (dd, J = 7 .6,1.9,1H),7.09–7.04(m,2H),6.99(t,J=7.6,1H),6.34(d,J=7.8,1H),4.4 2(hept,J=6.0,1H),3.98(s,2H),2.98(q,J=7.5,2H),2.64–2.44(m,2H),1.4 0(t,J=7.5,3H),1.13(d,J=6.0,3H),1.01(t,J=7.5,3H),0.92(d,J=6.0,3H). 13 C NMR(101MHz, CDCl3)δ=161.1,159.4,155.1,141.8,141.6,140.5,133.6,131.4,130.5,129.5,127 .9,126.6,126.4,124.8,122.3,120.9,113.9,70.3,38.6,28.7,22.3,22.2,21.9,15.1,14.9.HPLC conditions: [Daicel CHIRALPAKAD-H (4.6mmΦ×250mmL, Particle Size: 5μm); hexane / 2-propanol=97 / 3; flow rate=1.0mL / min; detectionwavelength=270nm; t R =4.82(major),5.72(minor)min.[α] D 27 ℃=-78.20(c 0.85,CHCl3).HRMS(ESI)m / z calc'd for C 25 H 28 NO(M+H) + :358.2165,found:358.2177.

[0199] Example 40

[0200] In this example, (R)-4-(2-benzyloxy)phenyl)-2,3-diethyl-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0201]

[0202] Colorless oil (35.9 mg, 88% yield) 99.5:0.5er. 1 H NMR(400MHz, CDCl3)δ=7.51(d,J=7.5,1H),7.49–7.43(m,1H),7.23–7.17( m,2H),7.17–7.08(m,5H),7.03–6.96(m,3H),6.32(d,J=7.9,1H),5.03(AB ,J=12.6,1H),4.95(BA,J=12.6,1H),4.01(s,2H),3.07–2.94(m,2H),2.69 –2.58(m,1H),2.57–2.46(m,1H),1.42(t,J=7.6,3H),1.02(t,J=7.6,3H). 13 CNMR(101MHz, CDCl3)δ=161.4,159.6,155.6,141.7,141.2,140.4,137.1,133.5,131.5,130.4,129.7,128. 4,127.6,127.5,126.7,126.6,126.5,124.9,122.3,121.6,113.3,70.0,38.6,28.8,22.4,15.2,14.9.HPLC conditions: [Daicel CHIRALPAK AD-H (4.6mmΦ×250mm L, Particle Size: 5μm); hexane / 2-propanol=99 / 1; flow rate=1.0mL / min; detection wavelength=310nm; t R =11.46(major),12.21(minor)min.[α] D 27 ℃=-87.61(c 1.1,CHCl3).HRMS(ESI)m / z calc'd for C 29 H28 NO(M+H) + :406.2165,found:406.2171

[0203] Example 41

[0204] In this example, (R)-4-(2-methoxyphenyl)-2,3-dimethyl-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0205]

[0206] Colorless oil (31.0 mg, 98% yield) 96.5:3.5er. 1 H NMR(400MHz, CDCl3)δ=7.53–7.47(m,2H),7.22–7.16(m,1H),7.14–7.07(m,3H),7.06– 6.98(m,1H),6.45(d,J=7.8,1H),3.97(s,2H),3.69(s,3H),2.65(s,3H),2.06(s,3H). 13 C NMR(101MHz, CDCl3)δ=160.9,156.5,154.9,141.7,141.0,140.4,131.3,130.1,129.8 ,128.5,126.8,126.7,126.5,124.9,122.2,121.4,111.4,55.8,38.6,23.6,15.7.HPLC conditions: [Daicel CHIRALCEL OJ-H (4.6mmΦ×250mm L, Particle Size: 5μm); hexane / 2-propanol=95 / 5; flow rate=1.0mL / min; detection wavelength=280nm; t R =6.14(major),11.84(minor)min.[α] D 27 ℃=-37.66(c 0.57,CHCl3).HRMS(ESI)m / z calc'd for C 21 H 20 NO(M+H) + :302.1539,found:302.1537.

[0207] Example 42

[0208] In this example, (R)-4-(2-methoxyphenyl)-2,3-dipentyl-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0209]

[0210] Colorless oil (33.5 mg, 81% yield) 98.5:1.5er. 1 H NMR(400MHz, CDCl3)δ=7.54–7.43(m,2H),7.23–7.15(m,1H),7.14–7.05(m, 3H),7.03–6.97(m,1H),6.33(d,J=7.8,1H),3.98(s,2H),3.67(s,3H),3.00 –2.82(m,2H),2.55–2.46(m,1H),2.44–2.36(m,1H),1.90–1.76(m,2H),1.5 3–1.34(m,6H),1.20–1.11(m,4H),0.94(t,J=7.0,3H),0.78(t,J=6.8,3H). 13 CNMR(101MHz, CDCl3)δ=161.2,158.7,156.6,141.7,141.3,140.4,132.6,131.4,130.3,129.7,126.9,126.7,1 26.5,124.9,122.1,121.2,111.3,55.6,38.6,36.0,32.5,32.2,30.6,30.3,29.3,22.8,22.2,14.3,14.0.HPLC conditions: [Daicel CHIRALPAKAD-H (4.6mmΦ×250mm L, Particle Size: 5μm); hexane / 2-propanol=97 / 3; flow rate=1.0mL / min; detection wavelength = 290nm; t R =6.49(major),5.70(minor)min.[α] D 27 ℃=-39.89(c 0.93,CHCl3).HRMS(ESI)m / z calc'd for C 29 H 36 NO(M+H)+ :414.2791,found:414.2798.

[0211] Example 43

[0212] In this example, (R)-2,3-diethyl-4-(2-(4-methoxybenzyl)oxy)phenyl)-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0213] Colorless oil (43.2 mg, 99% yield) 99:1er. 1 H NMR(400MHz, CDCl3)δ=7.51(d,J=7.5,1H),7.49–7.43(m,1H),7.24–7.16(m,2H),7.16– 7.09(m,2H),6.99(t,J=7.6,1H),6.88(d,J=8.3,2H),6.64(d,J=8.6,2H),6.30(d,J=7.8 ,1H),4.94(AB,J=12.0,1H),4.87(BA,J=12.0,1H),4.06(s,2H),3.72(s,3H),3.03(q,J= 7.5,2H),2.69–2.57(m,1H),2.57–2.45(m,1H),1.43(t,J=7.5,3H),1.02(t,J=7.5,3H). 13 C NMR(101MHz, CDCl3)δ=160.5,159.1,158.6,155.5,142.4,141.6,139.9,134.3,132.2,130.1,129.9,129.0,1 28.3,127.1,126.9,126.8,124.9,122.4,121.6,113.7,113.5,70.0,55.3,38.2,28.2,22.3,15.2,14.9.HPLC conditions: [Daicel CHIRALPAKAD-H (4.6mmΦ×250mm L, ParticleSize: 5μm); hexane / 2-propanol=93 / 7; flow rate=1.0mL / min; detection wavelength=310nm; t R =6.54(major),7.23(minor)min.[α] D27 ℃=-101.3(c 1.15,CHCl3).HRMS(ESI)m / z calc'd for C 30 H 30 NO2(M+H) + :436.2271,found:436.2286.

[0214] Example 44

[0215] In this example, (R)-2,3-diethyl-4-(2-methoxymethoxy)phenyl)-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0216] White solid (35.6 mg, 97% yield) 1 H NMR(400MHz, CDCl3)δ=7.52–7.44(m,2H),7.33(d,J=8.4,1H),7.22–7.12(m,3H),7.05–6.96(m,1H),6.31(d,J=7.8,1H),5.02(d,J=6.9,1H),4. 97(d,J=6.9,1H),3.98(s,2H),3.13(s,3H),2.98(q,J=7.6,2H),2.68–2 .54(m,1H),2.57–2.43(m,1H),1.41(t,J=7.5,3H),1.03(t,J=7.5,3H). 13 C NMR (101MHz, CDCl3) δ = 161.3, 159.6, 154.2, 141.7, 141.2, 140.3, 133.5, 131.4, 130.3, 129.7, 127.6, 126. 7,126.6,124.9,122.4,122.1,114.9,94.2,56.0,38.6,28.7,22.4,15.1,14.8.HPLCconditions:[Daicel CHIRALPAKAD-H (4.6mmΦ×250mm L, Particle Size: 5μm); hexane / 2-propanol=97 / 3; flow rate=1.0mL / min; detection wavelength=290nm; t R =7.10(major),10.11(minor)min.[α] D27 ℃=-90.61(c 0.87,CHCl3).HRMS(ESI)m / z calc'd forC 24 H 26 NO2(M+H) + :360.1958,found:360.1978.

[0217] Example 45

[0218] In this example, (R)-4-benzofuran-7-yl-2,3-diethyl-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0219]

[0220] White solid (34.0 mg, 96% yield) 88.5:11.5er. 1 H NMR (400MHz, CDCl3) δ = 7.78 (dd, J = 7.8, 1.3, 1H), 7.53 (d, J = 2.2, 1H), 7.49 (d, J=7.5,1H),7.45–7.39(m,1H),7.22(dd,J=7.3,1.3,1H),7.15(td,J=7.4,1.1, 1H),6.92–6.84(m,2H),5.97(d,J=7.8,1H),4.02(s,2H),3.01(q,J=7.5,2H), 2.67–2.55(m,1H),2.51–2.39(m,1H),1.44(t,J=7.5,3H),0.97(t,J=7.5,3H). 13 C NMR (101MHz, CDCl3) δ = 161.6, 159.9, 152.2, 145.7, 141.8, 139.9, 138.7, 133.8, 131.5, 128.1, 12 6.8,126.7,125.0,124.7,123.5,122.0,121.9,121.5,106.8,38.6,28.7,22.5,15.4,14.8.HPLC conditions: [Daicel CHIRALPAK AD-H (4.6mmΦ×250mm L, Particle Size: 5μm); hexane / 2-propanol=90 / 10; flow rate=1.0mL / min; detection wavelength=230nm; tR =11.20(major),6.11(minor)min.[α] D 27 ℃=-52.68(c1.3,CHCl3).HRMS(ESI)m / z calc'd for C 24 H 22 NO(M+H) + :340.1696,found:340.1705.

[0221] Example 46

[0222] In this example, (R)-4-benzo[d][1,3]dioxol-4-yl)-2,3-diethyl-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0223] White solid (33.9 mg, 98% yield) 83.5:16.5er. 1 H NMR(400MHz, CDCl3)δ=7.52(d,J=7.5,1H),7.25–7.20(m,1H),7.10–7.05( m,1H),7.05–6.98(m,2H),6.76(dd,J=6.7,2.3,1H),6.53(d,J=7.8,1H),5. 93(d,J=1.3,1H),5.87(d,J=1.3,1H),3.99(s,2H),2.98(q,J=7.6,2H),2.7 1–2.61(m,1H),2.61–2.51(m,1H),1.40(t,J=7.5,3H),1.07(t,J=7.5,3H). 13C NMR(101MHz, CDCl3)δ=161.5,159.7,147.9,144.6,141.8,139.8,138.1,133.7,131.3,12 6.9,125.1,122.6,122.5,122.2,119.3,108.7,101.1,38.5,28.6,22.4,15.3,14.8.HPLC conditions: [Daicel CHIRALPAK AD-H (4.6mmΦ×250mm L, Particle Size: 5μm); hexane / 2-propanol=97 / 3; flow rate=1.0mL / min; detection wavelength=270nm; t R =9.89(major),11.01(minor)min.[α] D 27 ℃=-48.44(c1.1,CHCl3).HRMS(ESI)m / z calc'd for C 23 H 22 NO2(M+H) + :344.1645,found:344.1651.

[0224] Example 47

[0225] In this example, (R)-2,3-dihydrobenzo[1,4]dioxin-5-yl)-2,3-diethyl-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0226]

[0227] White solid (34.2 mg, 96% yield) 97:3er. 1H NMR(400MHz, CDCl3)δ=7.52–7.48(m,1H),7.23–7.17(m,1H),7.09–6.97(m ,3H),6.73(dd,J=7.3,1.8,1H),6.43(d,J=7.8,1H),4.29–4.18(m,2H),4. 16–4.09(m,1H),4.09–4.02(m,1H),3.98(s,2H),2.98(q,J=7.5,2H),2.69 –2.58(m,1H),2.57–2.47(m,1H),1.41(t,J=7.5,3H),1.05(t,J=7.5,3H). 13 C NMR (101MHz, CDCl3) δ=161.3,159.6,144.2,141.7,140.8,140.2,140.1,133.5,131.4,126.9,126.8,1 26.6,125.0,122.1,122.0,121.8,117.4,64.5,38.6,28.6,22.4,15.2,14.8.HPLCconditions:[Daicel CHIRALPAKAD-H (4.6mmΦ×250mm L, Particle Size: 5μm); hexane / 2-propanol=93 / 7; flow rate=1.0mL / min; detection wavelength=250nm; t R =7.45(major),9.65(minor)min.[α] D 27 ℃=-138.0(c 0.93,CHCl3).HRMS(ESI)m / z calc'd forC 24 H 24 NO2(M+H) + :358.1802,found:358.1810.

[0228] Example 48

[0229] In this example, (R)-2,3-diethyl-4-(2-(3-methylbut-2-en-1-yl)oxy)phenyl)-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0230]

[0231] Colorless oil (32.4 mg, 85% yield) 98:2er. 1 H NMR(400MHz, CDCl3)δ=7.53–7.41(m,2H),7.19–7.15(m,1H),7.15–7.05(m ,3H),7.02–6.96(m,1H),6.31(d,J=7.8,1H),5.15–5.08(m,1H),4.42(d,J =6.4,2H),3.98(s,2H),2.98(q,J=7.5,2H),2.65–2.54(m,1H),2.53–2.40 (m,1H),1.58(s,3H),1.47(s,3H),1.40(t,J=7.5,3H),1.01(t,J=7.5,3H). 13 C NMR(101MHz, CDCl3)δ=161.2,159.4,155.8,141.7,141.6,140.5,137.2,133.7,131.5,130.3,129.5,127 .4,126.7,126.4,124.8,122.3,121.1,120.2,113.2,65.3,38.6,28.7,25.7,22.4,18.1,15.1,14.9.HPLC conditions: [Daicel CHIRALPAK AD-H (4.6mmΦ×250mm L, Particle Size: 5μm); hexane / 2-propanol=97 / 3; flow rate=1.0mL / min; detectionwavelength=270nm; t R =4.68(major),5.56(minor)min.[α] D 27 ℃=-89.26(c 0.85,CHCl3).HRMS(ESI)m / z calc'd for C 27 H 30 NO(M+H) + :384.2322,found:384.2343

[0232] Example 49

[0233] In this example, (R)-2,3-diethyl-4-o-tolyl-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0234]

[0235] Colorless oil (30.3 mg, 80% yield) 76:24er. 1 H NMR (400MHz, CDCl3) δ = 7.50 (d, J = 7.5, 1H), 7.46–7.31 (m, 3H), 7.22–7.12 (m, 2H), 7.03–6.96 (m, 1H), 6.17 (d, J = 7.8, 1H), 3. 99(s,2H),2.98(q,J=7.5,2H),2.66–2.54(m,1H),2.46–2.32(m,1H),1.98(s,3H),1.41(t,J=7.5,3H),1.01(t,J=7.5,3H). 13 C NMR (101MHz, CDCl3) δ = 161.6, 160.1, 143.6, 141.7, 140.2, 137.5, 135.6, 132.6, 130.8, 130. 5,128.6,128.3,126.9,126.6,126.5,124.9,122.0,38.7,28.7,22.0,19.8,15.1,14.8.HPLC conditions: [Daicel CHIRALPAK AD-H (4.6mmΦ×250mm L, Particle Size: 5μm); hexane / 2-propanol=93 / 7; flow rate=1.0mL / min; detection wavelength=310nm; t R =7.66(major),4.75(minor)min.[α] D 27 ℃=-26.95(c 1.1,CHCl3).HRMS(ESI)m / z calc'd for C 23 H 24 N(M+H) + :314.1903,found:314.1904.

[0236] Example 50

[0237] In this example, (R)-2,3-diethyl-4-naphthalen-1-yl-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0238]

[0239] White solid (29.6 mg, 84% yield) 77:23er. 1 H NMR (400MHz, CDCl3) δ = 8.03 (d, J = 8.3, 1H), 7.98 (d, J = 8.2, 1H), 7.68–7.59 (m, 1H),7.53–7.44(m,2H),7.44–7.35(m,2H),7.34–7.28(m,1H),7.16–7.05(m,1 H),6.87–6.71(m,1H),5.81(d,J=7.8,1H),4.05(s,2H),3.03(q,J=7.5,2H),2 .70–2.45(m,1H),2.40–2.21(m,1H),1.47(t,J=7.5,3H),0.95(t,J=7.5,3H). 13 C NMR(101MHz, CDCl3)δ=161.6,160.1,142.4,141.7,139.8,135.7,133.8,133.7,131.8,131.4,12 8.5,126.7,126.5,126.4,126.3,125.8,125.6,124.9,122.5,38.7,28.7,22.4,15.8,14.9.HPLC conditions: [Daicel CHIRALPAK AD-H (4.6mmΦ×250mm L, Particle Size: 5μm); hexane / 2-propanol=93 / 7; flow rate=1.0mL / min; detectionwavelength=270nm; t R =7.88(major),6.13(minor)min.[α] D 27 ℃=-40.03(c 1.2,CHCl3).HRMS(ESI)m / z calc'd for C 26 H 24 N(M+H) + :350.1903,found:350.1909.

[0240] Example 51

[0241] In this example, (R)-2,3-diethyl-6,7-dimethoxy-4-(2-methoxyphenyl)-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0242] White solid (37.6 mg, 97% yield) 97.5:2.5er. 1 H NMR (400MHz, CDCl3) δ=7.52–7.42(m,1H),7.19–7.16(m,1H),7.13(d,J=7.3,1H),7.09(d,J=8.7,1H),7.03(s,1H),5.79(s,1H),3.89(s,2H) ,3.87(s,3H),3.68(s,3H),3.42(s,3H),2.96(q,J=7.5,2H),2.65–2. 54(m,1H),2.54–2.43(m,1H),1.40(t,J=7.5,3H),1.02(t,J=7.5,3H). 13 C NMR (101MHz, CDCl3) δ=161.3,157.9,156.9,148.4,148.1,139.8,134.3,133.3,132.7,131.8,130 .7,129.6,126.8,121.2,111.2,108.0,105.1,56.1,55.7,55.3,38.3,28.5,22.4,15.1,14.9.HPLC conditions: [Daicel CHIRALCEL OD-H (4.6mmΦ×250mm L, Particle Size: 5μm); hexane / 2-propanol=90 / 10; flow rate=1.0mL / min; detection wavelength=330nm; t R =7.77(major),9.02(minor)min.[α] D 27 ℃=-75.59(c0.93,CHCl3).HRMS(ESI)m / z calc'd for C 25 H 28 NO3(M+H) + :390.2064,found:390.2074.

[0243] Example 52

[0244] In this example, (R)-2,3-diethyl-4-(2-fluorophenyl)-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0245]

[0246] Colorless oil (31.4 mg, 98% yield) 93:7er. 1 H NMR (400MHz, CDCl3) δ=7.59–7.49(m,2H),7.37–7.24(m,3H),7.24–7.18(m,1H),7.09–6.98(m,1H),6.31(d,J=7.8,1 H),4.04(s,2H),3.01(q,J=7.5,2H),2.67–2.56(m,1H),2.56–2.45(m,1H),1.42(t,J=7.5,3H),1.04(t,J=7.5,3H). 13 C NMR (101MHz, CDCl3) δ=161.16,159.39,159.37(d,J=246.0),141.75,139.56,138.28,133.82,131.80,130.82(d,J=3.3),130.50(d,J= 7.7),127.07,126.94,125.35(d,J=17.7),125.13,124.91(d,J=3.6),121.96,116.42(d,J=21.8),38.42,28.39,22.39,15.08,14.81. 19 F NMR (376MHz, CDCl3)δ=-113.6–-113.6(m).HPLCconditions: [Daicel CHIRALPAKAD-H (4.6mmΦ×250mm L, Particle Size: 5μm); hexane / 2-propanol=93 / 7; flow rate=1.0mL / min; detection wavelength=300nm; t R =9.58(major),5.53(minor)min.[α] D 27 ℃=5.30(c 1.4,CHCl3).HRMS(ESI)m / z calc'd forC 22 H21 FN(M+H) + :318.1653,found:318.1655.

[0247] Example 53

[0248] In this example, (R)-2,3-diethyl-4-(2-fluoro-4-methylphenyl)-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0249]

[0250] Colorless oil (31.2 mg, 94% yield) 93:7er. 1 H NMR (400MHz, CDCl3) δ = 7.51 (d, J = 7.5, 1H), 7.24–7.17 (m, 1H), 7.16–7.08 (m, 3H), 7.08–7.01 (m, 1H), 6.39 (d, J = 7. 8,1H),3.99(s,2H),2.98(q,J=7.6,2H),2.65–2.44(m,2H),2.51(s,3H),1.40(t,J=7.5,3H),1.03(t,J=7.5,3H). 13 C NMR (101MHz, CDCl3) δ = 161.50, 159.79, 159.24 (d, J = 245.3), 141.79, 140.89 ( d, J = 7.6), 139.95, 137.93, 133.69, 131.54, 130.47 ( d, J = 3.8), 12 6.83,126.79,125.59(d,J=3.1),125.05,122.33(d,J=17.8),121.99,1 16.86(d,J=21.7),38.61,28.70,22.37,21.49(d,J=1.6),15.13,14.78. 19 F NMR (376MHz, CDCl3) δ = -114.7–-114.8 (m). HPLC conditions: [Daicel CHIRALPAK AD-H (4.6mmΦ×250mm L, Particle Size: 5μm); hexane / 2-propanol = 97 / 3; flow rate = 1.0mL / min; detection wavelength = 310nm; t R=10.72(major),6.00(minor)min.[α] D 27 ℃=-1.45(c 1.2,CHCl3).HRMS(ESI)m / z calc'dfor C 23 H 23 FN(M+H) + :332.1809,found:332.1822.

[0251] Example 54

[0252] In this example, (R)-2,3-diethyl-4-(2-fluoro-4-methoxyphenyl)-9H-indeno[2,1-b]pyridine was prepared, and its structural formula is as follows:

[0253]

[0254] Colorless oil (31.6 mg, 91% yield) 91:9er. 1 H NMR (400MHz, CDCl3) δ=7.51(d,J=7.6,1H),7.24–7.19(m,1H),7.18–7.11(m,1H),7.09–7.03(m,1H),6.91–6.82(m,2H),6.44(d,J=7. 8,1H),3.99(s,2H),3.93(s,3H),2.97(q,J=7.6,2H),2.67–2.56(m,1H),2.56–2.43(m,1H),1.40(t,J=7.5,3H),1.03(t,J=7.5,3H). 13 C NMR (101MHz, CDCl3) δ=161.48,161.22(d,J=3.4),159.95(d,J=238.2),159.77,141.80,139.98,137.76,134.06,131.91,131.15(d,J=5.3 ),126.89,126.84,125.08,122.02,117.41(d,J=18.1),110.76(d,J=3.1),102.31(d,J=25.6),55.81,38.62,28.71,22.37,15.14,14.81. 19F NMR (376MHz, CDCl3) δ = -111.5 (t, J = 9.6). HPLC conditions: [Daicel CHIRALPAK AD-H (4.6mmΦ×250mm L, Particle Size: 5μm); hexane / 2-propanol = 93 / 7; flow rate = 1.0mL / min; detection wavelength = 270nm; t R =7.25(major),5.08(minor)min.[α] D 27 ℃=-4.60(c 1.0,CHCl3).HRMS(ESI)m / z calc'd for C 23 H 23 FNO(M+H) + :348.1758,found:348.1763.

[0255] Example 55

[0256] In this example, (R)-methyl-4-(2,3-diethyl-9H-indeno[2,1-b]pyridin-4-yl)-3-fluorobenzoate was prepared, and its structural formula is as follows:

[0257] Colorless oil (34.9 mg, 93% yield) 95.5:4.5er. 1 H NMR(400MHz, CDCl3)δ=8.03(d,J=7.8,1H),7.96(d,J=9.4,1H),7.52(d,J=7.5,1H),7.44–7.34(m,1H),7.26–7.16(m,1H),7.06–6.96(m,1H) ,6.29(d,J=7.8,1H),4.03–3.99(m,5H),2.98(q,J=7.5,2H),2.63–2. 51(m,1H),2.51–2.39(m,1H),1.40(t,J=7.5,3H),1.01(t,J=7.6,3H). 13C NMR (101MHz, CDCl3) δ = 165.90 (d, J = 2.8), 161.73, 159.97, 159.28 (d, J = 24 7.4),141.85,139.40,136.63,132.96,132.61(d,J=7.3),131.20(d,J=3. 3),130.90,130.59(d,J=18.2),127.09,126.97,126.02(d,J=3.4),125.2 3,121.75,117.56(d,J=23.8),52.73,38.58,28.63,22.44,15.06,14.70. 19 F NMR (376MHz, CDCl3) δ = -112.4 (t, J = 8.4). HPLC conditions: [Daicel CHIRALPAK AD-H (4.6mmΦ×250mm L, Particle Size: 5μm); hexane / 2-propanol = 97 / 3; flow rate = 1.0mL / min; detection wavelength = 250nm; t R =6.94(major),6.11(minor)min.[α] D 27 ℃=-1.14(c 0.88,CHCl3).HRMS(ESI)m / z calc'dforC 24 H 23 FNO2(M+H) + :376.1707,found:376.1724.

[0258] The present invention illustrates the detailed methods and specific products of the present invention through the above-mentioned embodiments, but the present invention is not limited to the above-mentioned detailed methods and specific products. That is, it does not mean that the present invention must rely on the above-mentioned detailed methods to be implemented or is limited to the reported products. It should be understood by those skilled in the art that any improvements to the present invention, equivalent replacement of various raw materials of the products of the present invention, addition of auxiliary components, selection of specific methods, etc., as well as modification and transformation based on the skeleton of the reported products in the present invention, all fall within the scope of protection and disclosure of the present invention.

[0259] The embodiments of the present invention are described as examples, but are not limited to the contents described in the present invention. Modifications made within the scope of the present invention or equivalent contents added in the claims are also possible.

Claims

1. A method for preparing 1-azafluorene containing axial chirality, characterized in that: The method comprises the following steps: stirring a nickel catalyst, a chiral ligand, a Lewis acid, an acetylene nitrile compound IV and an acetylene compound V in a solvent, and separating and purifying the mixture after the reaction to obtain an axial chiral 1-azafluorene compound VI; where R 4 is selected from alkyl, alkoxy and fluorine; R 5 、R 6 is selected from an alkyl group; the nickel catalyst is Ni(COD)2; the chiral ligand is any one of (R)-tol-BINAP, (R)-xyl-BINAP, (R)-8H-BINAP, (R)-SegPhos, (R)-SynPhos, (R)-MeO-BIPHEP, and (R)-DM-SegPhos, and the specific structure is shown in the following formula; The Lewis acid is ZnBr2; the solvent is any one of tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane, toluene, 1,2-dichloroethane and acetonitrile; and the reaction temperature during stirring in the solvent is 40-60 degrees Celsius.

2. The method for preparing 1-azafluorene containing axial chirality according to claim 1, characterized in that: The separation and purification methods used include suction filtration, column chromatography and recrystallization.

3. The method for preparing 1-azafluorene containing axial chirality according to claim 2, characterized in that: Column chromatography is performed on 200-300 mesh silica gel, and the eluent is a mixture of two or more of petroleum ether, ethyl acetate, dichloromethane, toluene, and triethylamine.

Images