Aza-biaryl compound, preparation method thereof and application of aza-biaryl compound in preparation of aza-helicene compound

Abstract

The invention discloses an aza-biaryl compound, a preparation method thereof and an application of the aza-biaryl compound in preparation of an aza-helicene compound, the aza-biaryl compound has the following structural general formula: # imgabs0 #, in which R1 is selected from one of hydrogen, alkyl, alkoxy and substituted or unsubstituted phenyl, or is cyclized with any two adjacent sites of aza-biaryl to form a benzene ring; ar is substituted aryl; and R3 is selected from hydrogen, substituted alkyl and substituted phenyl. The aza-biaryl compound can be prepared by reacting bromine-substituted benzoquinoline, aryl iodide and alkyne in the presence of a palladium catalyst, an organic ligand, an alkali reagent and a solvent through multi-component C-H activation series connection. A series of aza-helicene compounds can be prepared from the compound through one-step catalytic cyclization of a platinum catalyst or an acid catalyst. The preparation method has the advantages of simple steps, mild reaction, easily available raw materials and good substrate universality, and can efficiently construct the aza-biaryl compound and the aza-helicene compound.

Description

Technical Field

[0001] The present invention relates to the fields of organic synthesis, material science, biomedicine, and in particular to an azabiaryl compound and a preparation method thereof and an application thereof in the preparation of an azahelicene compound. Background Art

[0002] Helicene is composed of ortho-fused benzene rings or heteroaromatic rings. Since it was first synthesized in 1903, it has attracted the attention of chemists due to its inherent chirality, unique deformability and structural complexity (Chem. Rev. 2012, 112, 1463). Helicene has been widely studied and applied in the fields of azographene, fluorescent dyes, DNA intercalation reagents and asymmetric catalysis.

[0003]

[0004] However, the synthesis of azaspiricene fused ring structures is extremely challenging, and current methods often require multi-step synthesis, which is cumbersome and has low yields. In addition, most existing methods for synthesizing helicene require highly pre-functionalized substrates, require multi-step reactions, and have cumbersome operation steps, which leads to limitations in product types (Chem. Rev. 2019, 119, 8846).

[0005] Therefore, there is an urgent need for a synthetic method that has readily available raw materials and can simply and efficiently prepare different types of azaspirole compounds. Summary of the invention

[0006] To solve the above problems, the present invention provides an azabiaryl compound and a preparation method thereof and an application thereof in the preparation of an azahelicene compound. Benzoquinoline, aryl iodide and alkyne of 10-bromo-substituted structural units, which are readily available raw materials, are used as substrates. In the presence of an organic ligand and an alkaline reagent, a palladium catalyst and norbornene are used for synergistic catalysis to construct an azabiaryl compound in one step through a multi-component CH activation tandem strategy. The azabiaryl compound can be cyclized in the next step under the catalysis of platinum tetrachloride or trifluoromethanesulfonic acid to prepare an azahelicene compound.

[0007] Specifically, the present invention provides the following technical solutions:

[0008] The first aspect of the present invention provides an azabiaryl compound, wherein the azabiaryl compound has the following general structural formula:

[0009]

[0010] Among them, R 1 The substitution site is any one of 2-9, selected from hydrogen, alkyl, substituted aryl; or R 1 Any two sites adjacent to the azabiaryl group are cyclized to form a benzene ring;

[0011] Ar is R 2 Substituted aryl, the R 2 Selected from hydrogen, halogen, alkyl, alkoxy, ester,

[0012] One or more of, or R 2 Cyclize with any two adjacent sites of the aromatic group in Ar to form a benzene ring; the aromatic group is phenyl, pyridyl or benzothienyl;

[0013] R 3 is selected from one of hydrogen, silyl, substituted or unsubstituted alkyl, and substituted or unsubstituted phenyl; the substituent in the substituted alkyl is selected from one or more of the following groups: hydrogen, benzyloxy, benzoyloxy, phenoxycarbonyl, The substituent in the substituted phenyl group is a C2-C4 alkoxy group.

[0014] Furthermore, R 1 It is selected from one of hydrogen, C1-C4 alkyl, and C6-C7 substituted phenyl, more preferably hydrogen, methyl, phenyl, or methoxy substituted phenyl.

[0015] Furthermore, R 2 It is selected from one of hydrogen, halogen, C1-C3 alkyl, C1-C7 alkoxy, and ester, more preferably one or more of hydrogen, chlorine, methyl, methoxy, methoxymethyl, and methoxycarbonyl, or it is cyclized with any two adjacent sites of the aromatic group in Ar to form a benzene ring.

[0016] Furthermore, R 3 Preferred are hydrogen, trimethylsilyl, C2-C4 alkyl (eg butyl), methoxy-substituted phenyl, benzyloxy-substituted C2-C4 alkyl, benzoyloxy-substituted C2-C4 alkyl or phenoxycarbonyl-substituted C2-C4 alkyl.

[0017] Furthermore, the azabiaryl compound is one of the compounds shown in the following structures:

[0018]

[0019]

[0020] The second aspect of the present invention provides a method for preparing the azabiaryl compound according to the first aspect, comprising the following steps:

[0021] The compound represented by formula I, the compound represented by formula II and the compound represented by formula III are reacted in the presence of norbornene, a palladium catalyst, an organic ligand, an alkaline reagent and a solvent to obtain the azabiaryl compound;

[0022] The structures of the compounds shown in the above formula I to formula III are as follows:

[0023]

[0024] Wherein, M is H or KF3B-.

[0025] Furthermore, the compound represented by formula I is selected from but not limited to one of the compounds represented by the following structures:

[0026]

[0027] Furthermore, the compound represented by formula II is selected from but not limited to one of the compounds represented by the following structures:

[0028]

[0029] Furthermore, the compound represented by formula III is selected from but not limited to one of the following compounds represented by alkyne structures:

[0030]

[0031] Furthermore, the molar ratio of the compound represented by Formula I to the compound represented by Formula II and the compound represented by Formula III is preferably 1:(1-1.5):(1-2), for example 1:1:1.

[0032] Furthermore, the palladium catalyst is selected from one or more of palladium acetate, palladium chloride, palladium iodide, palladium trifluoroacetate, tetrakis(triphenylphosphine)palladium, bis(triphenylphosphine)palladium chloride, palladium(II)chlorobis(acetonitrile), tris(dibenzylideneacetone)dipalladium(0), bis(dibenzylideneacetone)palladium, and bis(acetylacetone)palladium(II).

[0033] Furthermore, the organic ligand is preferably one or more of triphenylphosphine, tri(2-furyl)phosphine, diphenylmethylphosphine, bis(2-diphenylphosphinophenyl)ether, 2-dicyclohexylphosphino-2'-methylbiphenyl, 1,1'-bis(diphenylphosphino)ferrocene, 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl, 4,5-bis(diphenylphosphino)-9,9-dimethyloxanthene, and bis(diphenylphosphino)methane.

[0034] Furthermore, the alkaline reagent is preferably one or more of potassium carbonate, sodium carbonate, cesium carbonate, lithium carbonate, potassium phosphate, potassium hydroxide, and potassium bicarbonate.

[0035] Furthermore, the solvent is preferably one or more of ethylene glycol dimethyl ether, diethyl ether, methyl tert-butyl ether, acetonitrile, 1,4-dioxane, tetrahydrofuran, N,N-dimethylformamide, N,N-dimethylacetamide, toluene, chlorobenzene, and fluorobenzene.

[0036] Furthermore, the norbornene is preferably simple norbornene without any substituent.

[0037] Furthermore, the molar ratio of the compound represented by formula I to the palladium catalyst, norbornene, organic ligand, and alkaline reagent is preferably 1:0.1:(1-2):(0.1-0.2):(2.5-4.5).

[0038] Furthermore, the reaction temperature of the reaction is 90-120° C., and the reaction time is 24-48 hours.

[0039] Furthermore, the preparation method further comprises the following steps: after the reaction is completed, filtering the reaction solution through diatomaceous earth, washing with ethyl acetate, vacuum concentrating, and separating by column chromatography to obtain the azabiaryl compound.

[0040] The third aspect of the present invention provides a use of the azabiaryl compound described in the first aspect in the preparation of an azahelicene compound, wherein the azabiaryl compound is subjected to a ring-closing reaction in the presence of a catalyst and a solvent to obtain the azahelicene compound; the catalyst is platinum tetrachloride or trifluoromethanesulfonic acid;

[0041] The azahelicene compounds have the following general structural formulas IV-1 to IV-4:

[0042]

[0043] Where Z is C or N, R 3 One selected from hydrogen, silyloxy, and substituted or unsubstituted phenyl.

[0044] Further, when R of the azabiaryl compound is 3 When it is hydrogen, platinum tetrachloride is used as a catalyst for the ring-closing reaction.

[0045] Further, when R of the azabiaryl compound is 3 When R is a silyl group, the azabiaryl compound is first subjected to a deprotection treatment, and then a ring-closing reaction is carried out using platinum tetrachloride as a catalyst. In some preferred embodiments, the deprotection treatment specifically comprises: 3 The azabiaryl compound which is a silyl group reacts with tetrabutylammonium fluoride (TBAF) in the presence of a solvent to obtain a deprotected product.

[0046] Furthermore, when the catalyst is platinum tetrachloride, the solvent is preferably 1,2-dichloroethane; the molar ratio of the nitrogen heterobiaryl compound to platinum tetrachloride is 1:(0.1-0.2), the reaction temperature of the ring-closure reaction is preferably 120-130°C, and the reaction time is preferably 16-24h.

[0047] Further, the azahelicene compounds prepared using platinum tetrachloride as a catalyst include but are not limited to the compounds shown in the following structure:

[0048]

[0049] Further, when R of the azabiaryl compound is 3 When it is a substituted or unsubstituted phenyl group, trifluoromethanesulfonic acid is used as a catalyst for the ring-closing reaction; the solvent is preferably dichloromethane; the molar ratio of the nitrogen heterobiaryl compound to trifluoromethanesulfonic acid is preferably 1:(2-4), the reaction temperature of the ring-closing reaction is preferably 20-30°C, and the reaction time is preferably 3-5h.

[0050] Further, the azaspirene compound prepared using trifluoromethanesulfonic acid as a catalyst includes but is not limited to the compound shown in the following structure:

[0051]

[0052] Compared with the prior art, the present invention has the following beneficial effects:

[0053] The present invention uses cheap and readily available industrial raw materials, bromine-substituted benzoquinoline, easily prepared aryl iodine reagents and alkynyl reagents as reaction substrates, and prepares azabiaryl compounds in a one-pot method through a multi-component CH bond activation strategy. The azabiaryl compound can be used as an azahelicene precursor, and can be ring-closed in one step under the action of a specific catalyst to obtain a variety of azahelicene compounds, including substituted aza[4]helicene and aza[5]helicene derivatives. Compared with the current traditional method for synthesizing azahelicene compounds with lengthy reaction steps and complex substrates, the preparation method provided by the present invention is simple and easy to operate, and has high step economy, providing a gentle, efficient and green channel for constructing azahelicene molecules.

[0054] The preparation method provided by the present invention has substrate universality and strong modifiability. Different substituents can be introduced into three reaction substrates to prepare azahelicene compounds with different substituents to meet different application requirements, including but not limited to optoelectronic materials, biosensors, fluorescent probes, organic small molecule catalysis, asymmetric catalysis, etc., in which the currently substituted aza[4]helicene derivatives and substituted aza[5]helicene derivatives have good application prospects. DETAILED DESCRIPTION

[0055] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those generally understood by those skilled in the art to which the present invention belongs. The terms used herein in the specification of the present invention are for the purpose of describing specific embodiments only and are not intended to limit the present invention. The term "and / or" used herein includes any and all combinations of one or more related listed items. The term "includes" or "comprising" described in the present invention means that it may include or contain other components in addition to the components described. The term "includes" or "comprising" described in the present invention may also be replaced by the closed form "for" or "consisting of..."

[0056] The present invention is further described below in conjunction with specific embodiments so that those skilled in the art can better understand the present invention and implement it, but the embodiments are not intended to limit the present invention.

[0057] Example 1

[0058] This example involves the synthesis of azabiaryl compound 35, and the specific operation is as follows:

[0059]

[0060] Under argon protection, a moderate magnetic particle was placed in a dry 35.0 mL pressure-resistant sealed tube, and Pd(OAc)2 (10 mol%), PPh3 (20 mol%), potassium carbonate (2.5 equiv.), ultra-dry ethylene glycol dimethyl ether (0.1 M), 10-bromobenzoquinoline (compound 1, 0.5 mmol, 1.0 equiv.), aryl iodide (compound 6, 1.5 equiv.), alkynyl compound (compound 25, 2.0 equiv.) were added. Then, the tube was tightly sealed, taken out of the glove box, and stirred at 100°C at 650 rpm for 24 hours. After the reaction was completed (monitored by thin layer chromatography), the mixture was cooled to room temperature.

[0061] Removal of the TMS protecting group: A THF solution of TBAF (1.0 M, 1.25 mmol, 2.5 equiv.) was then added, and the resulting reaction mixture was stirred for an additional 3 hours, then filtered through diatomaceous earth, the mixture was eluted with ethyl acetate (30 mL), and concentrated in vacuo. The crude product obtained by concentration was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 15 / 1) to give 106.4 mg of a yellow oily product with a yield of 73%.

[0062] The product was characterized and the results are as follows:

[0063] 1H NMR (400MHz, CDCl3) δ8.31 (d, J = 4.8Hz, 1H), 7.97 (d, J = 8.0Hz 1H),7.86(d,J=8.0Hz,1H),7.76(d,J=8.8Hz,1H),7.60(q,J=8.8,8.4Hz,2H),7.45(d,J=7.2Hz, 1H),7.25–7.18(m,2H),7.15(d,J=7.2Hz,1H),7.05(d,J=7.6Hz,1H),2.59(s,1H),2.44(s,3H).

[0064] 13 C NMR (101MHz, CDCl3) δ150.0,147.1,146.8,140.2,140.1,134.9,134.4,130.7,1 29.5,128.2,128.1,127.7,126.9,126.8,125.8,125.7,120.9,83.1,82.1,21.2.

[0065] HRMS(ESI)m / z:[M+H] + C 22 H 16 N + Calculated value: 294.1277; Test value: 294.1273.

[0066] The effects of different reaction conditions on the yield are studied, as shown in Table 1 below:

[0067] Table 1

[0068]

[0069]

[0070] Example 2

[0071] This example relates to the synthesis of azabiaryl compound 36, the structure of which is as follows:

[0072]

[0073] The preparation process of this compound differs from that of Example 1 only in that the aryl iodide is compound 7, and the other operations are the same, and 76.5 mg of a cyan oily product is obtained with a yield of 49%.

[0074] The product was characterized and the results are as follows:

[0075] 1H NMR (400MHz, CDCl3) δ8.34(dd,J=4.4,1.6Hz,1H),7.95(dd,J=8.0,2.0Hz,1H),7.85(d,J=8.0Hz,1H),7.75(d,J=8.8Hz,1H),7.63–7.5 6(m,2H),7.44(dd,J=7.2,1.2Hz,1H),7.28(t,J=8.0Hz,1H),7.19(dd,J=8.0,4.4Hz,1H),6.86–6.81(m,2H),3.88(s,3H),2.63(s,1H).

[0076] 13 C NMR (101MHz, CDCl3) δ160.5,151.8,147.3,146.7,139.4,135.0,134.4,130.6,129.4,1 28.9,128.2,128.1,126.9,126.8,125.8,121.2,121.0,110.3,107.8,83.2,79.5,55.9.

[0077] HRMS(ESI)m / z:[M+H] + C 22 H 16 NO + Calculated value: 310.1226; tested value: 310.1226.

[0078] Example 3

[0079] This example relates to the synthesis of azabiaryl compound 37, the structure of which is as follows:

[0080]

[0081] The preparation process of the compound differs from that of Example 1 only in that the aryl iodide is compound 8, and the other operations are the same, and 169.8 mg of a yellow solid product is prepared with a yield of 73%.

[0082] The product was characterized and the results are as follows:

[0083] 1H NMR (400MHz, CDCl3) δ8.32(dd,J=4.4,1.6Hz,1H),7.95(dd,J=8.0,2.0Hz,1H),7.86(dd,J=8.0,1.4Hz,1H),7.74(d,J=8.8Hz,1H),7.6 2–7.53(m,2H),7.40(dd,J=7.2,1.2Hz,1H),7.34(dd,J=8.0,1.2Hz,1H),7.24–7.17(m,2H),7.09(dd,J=7.6,1.2Hz,1H),2.65(s,1H).

[0084] 13 C NMR (101MHz, CDCl3) δ151.9,147.2,146.5,138.8,135.8,135.1,134.4,130.4,12 9.2,128.7,128.5,128.1,127.0,126.8,126.7,126.5,125.9,121.1,84.3,79.9.

[0085] HRMS(ESI)m / z:[M+H] + C 21 H 13 ClNO + Calculated value: 314.0731; tested value: 314.0730.

[0086] Example 4

[0087] This example relates to the synthesis of azabiaryl compound 38, the structure of which is as follows:

[0088]

[0089] The preparation process of the compound differs from that of Example 1 only in that the aryl iodide is compound 9, and the other operations are the same, and 137.7 mg of a yellow solid product is prepared with a yield of 85%.

[0090] The product was characterized and the results are as follows:

[0091] 1H NMR (400MHz, CDCl3) δ8.28(dd,J=4.4,2.0Hz,1H),7.95(dd,J=8.0,2.0Hz,1H),7.85(dd,J=8.0,1.6Hz,1H),7.75(d,J=8.8Hz,1H ),7.64–7.54(m,2H),7.45–7.38(m,2H),7.34(t,J=7.6Hz,1H),7.20–7.14(m,2H),4.69–4.54(m,2H),3.39(s,3H),2.59(s,1H).

[0092] 13 C NMR (101MHz, CDCl3) δ150.1,147.0,146.7,140.0,139.8,135.0,134.4,130.7,129.5,128.1 9,128.16,128.0,127.5,127.0,126.8,125.8,124.9,121.0,119.8,83.7,80.7,72.9,58.2.

[0093] HRMS(ESI)m / z:[M+H] + C 23 H 18 NO + Calculated value: 324.1383; tested value: 324.1381.

[0094] Example 5

[0095] This example relates to the synthesis of azabiaryl compound 39, the structure of which is as follows:

[0096]

[0097] The preparation process of this compound differs from that of Example 1 only in that the aryl iodide is compound 13, and the other operations are the same, and 103.3 mg of a yellow oily product is obtained with a yield of 67%.

[0098] The product was characterized and the results are as follows:

[0099] 1H NMR (400MHz, CDCl3) δ8.31(dd,J=4.4,2.0Hz,1H),7.91(dd,J=8.0,2.0Hz,1H),7.81(dd,J=8.0,1.2Hz,1H),7.71(d,J=8.8Hz,1H),7.59–7.51(m ,2H),7.42(dd,J=7.3,1.4Hz,1H),7.15(dd,J=8.0,4.4Hz,1H),7.11–7. 07(m,1H),6.95(d,J=7.6Hz,1H),2.53(s,1H),2.37(s,3H),2.28(s,3H).

[0100] 13 C NMR (101MHz, CDCl3) δ147.9,147.1,147.0,140.5,138.3,134.9,134.4,133.7,131.0,129.6 ,129.4,128.2,127.80,126.9,126.8,125.7,125.5,121.0,120.8,82.72,82.65,20.4,17.7.

[0101] HRMS(ESI)m / z:[M+H] + C 23 H 18 N + Calculated value: 308.1434; tested value: 308.1436.

[0102] Example 6

[0103] This example relates to the synthesis of azabiaryl compound 40, the structure of which is as follows:

[0104]

[0105] The preparation process of this compound differs from that of Example 1 only in that the aryl iodide is compound 10, and the other operations are the same, and 133.1 mg of a yellow oily product is obtained with a yield of 81%.

[0106] The product was characterized and the results are as follows:

[0107] 1H NMR (400MHz, CDCl3) δ8.33(dd,J=4.4,1.6Hz,1H),7.95(dd,J=8.0,1.6Hz,1H),7.84(d,J=8.0Hz,1H),7.73(d,J=8.8Hz,1H),7.62–7. 53(m,2H),7.39(d,J=7.2Hz,1H),7.29(d,J=8.4Hz,1H),7.19(dd,J=8.0,4.4Hz,1H),6.96(d,J=8.4Hz,1H),2.59(s.1H),2.50(s,3H).

[0108] 13 C NMR (101MHz, CDCl3) δ148.8,147.1,146.6,139.3,137.7,135.1,134.5,131.7,130.7,1 29.3,128.6,128.3,128.2,127.0,126.9,126.8,125.8,122.8,121.0,83.8,81.6,18.6.

[0109] HRMS(ESI)m / z:[M+H] + C 22 H 15 C1N + Calculated value: 328.0888; tested value: 328.0890.

[0110] Example 7

[0111] This example relates to the synthesis of azabiaryl compound 41, the structure of which is as follows:

[0112]

[0113] The preparation process of the compound differs from that of Example 1 only in that the aryl iodide is compound 11, and the other operations are the same, and 91.4 mg of a yellow oily product is obtained with a yield of 52%.

[0114] The product was characterized and the results are as follows:

[0115] 1H NMR (400MHz, CDCl3) δ8.27(dd,J=4.4,1.6Hz,1H),7.94(dd,J=8.0,2.0Hz,1H),7.8-7.79(m,2H),7.73(d,J=8.8Hz,1H),7.61 –7.53(m,2H),7.37(d,J=7.2Hz,1H),7.20-7.15(m,1H),7.08(dd,J=8.1,1.5Hz,1H),3.84(s,3H),2.72(s,3H),2.60(s,1H).

[0116] 13 C NMR (101MHz, CDCl3) δ168.3,154.0,147.1,146.4,142.0,139.4,135.1,134.4,130.2,129.9,1 29.2,128.4,128.1,127.7,127.0,126.8,125.8,125.7,123.0,121.1,84.3,81.5,51.9,19.2.

[0117] HRMS(ESI)m / z:[M+H] + C 24 H 18 NO2 + Calculated value: 352.1332; tested value: 352.1334.

[0118] Example 8

[0119] This example relates to the synthesis of azabiaryl compound 42, the structure of which is as follows:

[0120]

[0121] The preparation process of this compound differs from that of Example 1 only in that the aryl iodide is compound 12, and the other operations are the same, and 84.7 mg of a yellow oily product is obtained with a yield of 51%.

[0122] The product was characterized and the results are as follows:

[0123] 1H NMR(400MHz, DMSO-d6)δ8.37(dd,J=4.4,2.0Hz,2H),8.24–8.16(m,2H),8.12–8.05(m,2H),7.99–7.93( m,2H),7.85(t,J=7.6Hz,1H),7.69(t,J=6.8Hz,1H),7.65–7.58(m,2H),7.47–7.38(m,2H),4.06(s,1H).

[0124] 13 C NMR(101MHz,DMSO-d6)δ149.6,148.1,146.7,140.3,136.6,135.4,134.1,132.3,132.1,129.5,129.4 ,129.24,129.19,129.1,128.3,128.2,127.9,127.8,127.0,126.7,126.5,122.4,116.7,88.6,82.2.

[0125] HRMS(ESI)m / z:[M+H] + C 25 H 16 N + Calculated value: 330.1277; tested value: 330.1273.

[0126] Example 9

[0127] This example relates to the synthesis of azabiaryl compound 43, the structure of which is as follows:

[0128]

[0129] The preparation process of the compound differs from that of Example 1 only in that the aryl iodide is compound 14, and the other operations are the same, and 120.4 mg of a yellow oily product is obtained with a yield of 78%.

[0130] The product was characterized and the results are as follows:

[0131] 1H NMR (400MHz, CDCl3) δ8.46-8.41(m,1H),8.07(d,J=8.0Hz,1H),7.95(d,J=8.0Hz,1H),7.86(d,J=8.8Hz,1H),7.73–7.66(m ,2H),7.54(d,J=7.2Hz,1H),7.31(dd,J=8.0,4.4Hz,1H),7.07(s,1H),7.00(s,1H),2.61(s,1H),2.49(s,3H),2.38(s,3H).

[0132] 13 C NMR (101MHz, CDCl3) δ149.9,147.1,146.9,140.4,140.0,137.6,134.9,134.4,130.8,129. 6,128.2,128.0,127.7,126.9,126.8,126.5,125.7,120.9,118.1,82.3,82.2,21.5,21.1.

[0133] HRMS(ESI)m / z:[M+H] + C 23 H 18 N + Calculated value: 308.1434; tested value: 308.1436.

[0134] Example 10

[0135] This example relates to the synthesis of azabiaryl compound 44, the structure of which is as follows:

[0136]

[0137] The preparation process of the compound differs from that of Example 1 only in that the aryl iodide is compound 17, and the other operations are the same, and 40.5 mg of a yellow solid product is prepared with a yield of 27%.

[0138] The product was characterized and the results are as follows:

[0139] 1H NMR (400MHz, CDCl3) δ8.30(dd,J=4.4,1.6Hz,1H),7.93(dd,J=8.0,1.6Hz,1H),7.84(dd,J=8.4Hz,1.6Hz,1H),7.75(d,J=8.8Hz,1H),7.63(t, J=7.6Hz,1H),7.55(d,J=8.8Hz,1H),7.36(d,J=8.0Hz,1H),7.17(dd,J=8.0,4..0Hz,1H),7.05(s,2H),2.62(s,1H),2.39(s,3H),1.70(s,3H).

[0140] 13 C NMR (101MHz, CDCl3) δ149.4,147.5,146.8,139.4,137.7,135.0,134.6,132.8,130.3,129. 4,129.2,128.4,127.9,127.4,126.7,126.6,125.6,120.9,120.2,83.1,82.5,20.9,20.2.

[0141] HRMS(ESI)m / z:[M+H] + C 24 H 18 N + Calculated value: 308.1434; tested value: 308.1432.

[0142] Embodiment 11

[0143] This example relates to the synthesis of azabiaryl compound 45, the structure of which is as follows:

[0144]

[0145] The preparation process of this compound differs from that of Example 1 only in that the alkynyl compound is compound 26, no deprotection operation is required, the eluent for silica gel column chromatography is petroleum ether / ethyl acetate = 20 / 1, and the other operations are the same, and 69.6 mg of an orange solid product is prepared with a yield of 50%.

[0146] The product was characterized and the results are as follows:

[0147] 1H NMR (400MHz, CDCl3) δ8.35-8.30(m,1H),7.99–7.93(m,1H),7.83(dd,J=8.0,3.6Hz,1H),7.76(dd,J=8.8,4.0Hz,1H),7.64–7.55(m,2H ),7.47–7.39(m,1H),7.23–7.16(m,2H),7.15-7.07(m,2H),2.38(s,3H),1.73–1.63(m,2H),0.63–0.50(m,4H),0.45(t,J=4.4Hz,3H).

[0148] 13 C NMR (101MHz, CDCl3) δ149.4,147.1,147.0,140.9,138.9,134.8,134.4,130.9,129.7,128.2,127.8, 126.9,126.70,126.66,126.5,125.6,125.4,122.9,120.8,96.5,79.1,30.3,21.2,21.1,18.8,13.4.

[0149] HRMS(ESI)m / z:[M+H] + C 26 H 24 N + Calculated value: 350.1908; tested value: 350.1903.

[0150] Example 12

[0151] This example relates to the synthesis of azabiaryl compound 46, the structure of which is as follows:

[0152]

[0153] The preparation process of this compound differs from that of Example 1 only in that the alkynyl compound is compound 27, no deprotection operation is required, the eluent for silica gel column chromatography is petroleum ether / ethyl acetate = 30 / 1, and the other operations are the same, and 121.7 mg of a yellow solid product is prepared with a yield of 63%.

[0154] The product was characterized and the results are as follows:

[0155] 1H NMR (400MHz, CDCl3) δ8.30 (dd, J=4.4, 1.6Hz, 1H), 7.89 (dd, J=8.0, 1.6Hz, 1H) ,7.77(dd,J=8.0,1.2Hz,1H),7.69(d,J=8.8Hz,1H),7.56(t,J=7.6Hz,1H),7. 50(d,J=8.8Hz,1H),7.41(dd,J=7.2,1.2Hz,1H),7.25–7.15(m,5H),7.15–7.0 5(m,4H),4..09(s,2H),2.59–2.44(m,2H),2.35(s,3H),1.96(t,J=8.0Hz,2H).

[0156] 13 C NMR (101MHz, CDCl3) δ149.4,147.1,146.9,140.7,139.0,138.1,134.9,134.3,130.9,129.6,128.3,128.1,127.8,12 7.7,127.5,127.4(2C),127.0,126.9,126.7,126.6,125.6,125.4,122.4,120.9,92.4,80.3,72.5,68.1,21.1,20.4.

[0157] HRMS(ESI)m / z:[M+H] + C 31 H 26 NO + Calculated value: 428.2003; tested value: 428.2008.

[0158] Embodiment 13

[0159] This example relates to the synthesis of azabiaryl compound 47, the structure of which is as follows:

[0160]

[0161] The preparation process of this compound differs from that of Example 1 only in that the alkynyl compound is compound 28, and no deprotection operation is required. The other operations are the same, and 95.4 mg of a yellow oily product is prepared with a yield of 43%.

[0162] The product was characterized and the results are as follows:

[0163] 1H NMR(400MHz, CDCl3)δ8.32(dd,J=4.2,1.6Hz,1H),7.95(dd,J=8.0,1.6Hz,1H),7.80-7.75(m,3H),7.73(d,J=8.8Hz,1H),7.58–7.50(m,2H),7 .47–7.41(m,2H),7.29(t,J=7.6Hz,2H),7.22(t,J=7.6Hz,1H),7.18–7.11(m,3H),3.43(t,J=7.0Hz,2H),2.36(s,3H),2.13(t,J=7.2Hz,2H).

[0164] 13 C NMR (101MHz, CDCl3) δ165.0,146.0,145.9,145.7,139.5,138.2,134.1,133.3,131.8,129.9,128.9,128.5,128.4( 2C),127.3,127.2,127.0,126.1,126.0,125.8,125.7,124.60,124.56,121.1,119.9,90.4,79.6,61.6,20.2,18.6.

[0165] HRMS(ESI)m / z:[M+H] + C 31 H 24 NO2 + Calculated value: 442.1802; tested value: 442.1801.

[0166] Embodiment 14

[0167] This example relates to the synthesis of azabiaryl compound 48, the structure of which is as follows:

[0168]

[0169] The preparation process of this compound differs from that of Example 1 only in that the alkynyl compound is compound 29, and no deprotection operation is required. The other operations are the same, and 141.2 mg of a brown oily product is obtained with a yield of 61%.

[0170] The product was characterized and the results are as follows:

[0171] 1H NMR (400MHz, CDCl3) δ8.35 (dd, J=4.4, 2.0Hz, 1H), 7.97 (dd, J=8.0, 1.6Hz, 1H), 7. 85(dd,J=8.0,1.2Hz,1H),7.76(d,J=8.8Hz,1H),7.67–7.55(m,2H),7.46(dd,J=7 .2,1.2Hz,1H),7.34–7.28(m,2H),7.26–7.19(m,2H),7.18–7.11(m,3H),6.94(d, 8.0Hz,2H),2.39(s,3H),1.93–1.82(m,2H),1.74–1.65(m,2H),1.15–1.04(m,2H).

[0172] 13 C NMR (101MHz, CDCl3) δ171.6,150.6,149.4,147.2,146.9,140.8,139.1,135.0,134.4,130.9,129.6,129.4,128.3, 128.0,127.0,126.9,126.8,126.7,125.7,125.4,122.5,121.6,121.5,121.0,94.7,80.2,32.2,23.2,21.2,18.5.

[0173] HRMS(ESI)m / z:[M+H] + C 32 H 26 NO2 + Calculated value: 456.1958; tested value: 456.1957.

[0174] Embodiment 15

[0175] This example relates to the synthesis of azabiaryl compound 49, the structure of which is as follows:

[0176]

[0177] The preparation process of this compound differs from that of Example 1 only in that the alkynyl compound is compound 30, no deprotection operation is required, the eluent for silica gel column chromatography is petroleum ether / ethyl acetate = 15 / 1, no deprotection operation is required, and the other operations are the same, and 125.5 mg of a brown solid product is prepared with a yield of 58%.

[0178] The product was characterized and the results are as follows:

[0179] 1H NMR (400MHz, CDCl3) δ8.32(dd,J=4.4,1.6Hz,1H),7.90(dd,J=8.0,2.0Hz,1H),7.86(dd,J=7.6,1.2Hz,1H),7.78(d,J=8.8Hz,1H),7.64–7.5 5(m,2H),7.48(dd,J=7.2,1.2Hz,1H),7.26–7.17(m,2H),7.17–7.12(m ,2H),6.49–6.41(m,2H),6.40–6.29(m,2H),3.55(s,3H),2.45(s,3H).

[0180] 13 C NMR (101MHz, CDCl3) δ158.8,149.3,147.1,146.9,140.6,138.8,134.9,134.4,132.1,131.0,129.7,129.0,128. 2,128.1,127.9,127.2,127.0,126.8,126.7,125.7,125.5,122.4,121.0,115.8,113.3,95.6,87.8,55.1,21.2.

[0181] HRMS(ESI)m / z:[M+H] + C 29 H 22 NO + Calculated value: 440.1696; tested value: 440.1693.

[0182] Example 16

[0183] This example relates to the synthesis of azabiaryl compound 50, the structure of which is as follows:

[0184]

[0185] The preparation process of this compound is different from that of Example 1 only in that the aryl iodide is compound 10, the alkynyl compound is compound 30, no deprotection operation is required, the eluent for silica gel column chromatography is petroleum ether / ethyl acetate = 5 / 1, no deprotection operation is required, and the other operations are the same, and 103.8 mg of a yellow solid product is prepared with a yield of 48%.

[0186] The product was characterized and the results are as follows:

[0187] 1H NMR (400MHz, CDCl3) δ8.40(s,1H),8.18(s,1H),8.04-7.92(m,2H),7.87–7.79(m,1H),7.71-7.60(m ,2H),7.48(dd,J=7.6,3.6Hz,1H),7.29–7.21(m,1H),6.57–6.33(m,4H),3.63(s,3H),2.54(s,3H).

[0188] 13 C NMR (101MHz, CDCl3) δ159.9,148.8,147.4,146.5,145.4,142.9,135.8,135.2,134.6,133.3,132.8,1 31.2,131.1,129.7,129.0,128.1,127.1,126.9,126.1,121.3,114.1,113.6,100.6,84.8,55.2,18.2.

[0189] HRMS(ESI)m / z:[M+H] + C 28 H 20 ClN2O + Calculated value: 432.1259; tested value: 432.1262.

[0190] Embodiment 17

[0191] This example relates to the synthesis of azabiaryl compound 51, the structure of which is as follows:

[0192]

[0193] The preparation process of this compound differs from that of Example 1 only in that: the aryl iodide is compound 19, the alkynyl compound is compound 30, no deprotection operation is required, the eluent for silica gel column chromatography is petroleum ether / ethyl acetate = 15 / 1, no deprotection operation is required, and the other operations are the same, and 70.6 mg of a yellow oily product is prepared with a yield of 32%.

[0194] The product was characterized and the results are as follows:

[0195] 1H NMR(400MHz, CDCl3)δ8.44-8.34(m,1H),8.00(d,J=8.0Hz,1H),7.96–7.89(m,2H),7.84-7.74(m,3H),7.70–7.61(m ,2H),7.42–7.37(m,1H),7.35–7.30(m,1H),7.26–7.21(m,1H),6.89–6.82(m,2H),6.63–6.55(m,2H),3.64(s,3H).

[0196] 13 C NMR (101MHz, CDCl3) δ159.1,151.4,147.5,146.2,139,138.7,135.1,134.8,132.6,132.5,132.0,130.1,12 9.5,128.0,127.2,127.0,126.1,124.3,124.2,123.0,122.1,121.3,115.6,114.9,113.6,92.9,82.6,55.2.

[0197] HRMS(ESI)m / z:[M+H] + C 30 H 20 NOS + Calculated value: 442.1260; tested value: 442.1259.

[0198] Embodiment 18

[0199] This example relates to the synthesis of azabiaryl compound 52, the structure of which is as follows:

[0200]

[0201] The preparation process of the compound differs from that of Example 1 only in that the aryl iodide is compound 13, the alkynyl compound is compound 31, no deprotection operation is required, the eluent for silica gel column chromatography is petroleum ether / ethyl acetate = 15 / 1, no deprotection operation is required, and the other operations are the same, and 107.4 mg of a yellow oily product is prepared with a yield of 52%.

[0202] The product was characterized and the results are as follows:

[0203] 1H NMR (400MHz, CDCl3) δ8.28(dd,J=4.4,2.0Hz,1H),7.79–7.72(m,2H),7.67(d,J=8.8Hz,1H),7.51(t,J=7.6Hz,1H),7.47–7.40(m,2H),7. 07(s,2H),7.00(dd,J=8.0,4.4Hz,1H),6.38–6.33(d,J=4.0Hz,2H),6.33–6.27(d,J=4.0Hz,2H),3.41(s,3H),2.36(s,3H),2.24(s,3H).

[0204] 13 C NMR (101MHz, CDCl3) δ158.7,147.2,147.0,146.9,140.9,137.0,134.9,134.4,133.7,132.0,131.3,129.7, 128.9,128.1,127.8,126.9,126.7,125.6,125.2,122.5,120.8,115.8,113.3,95.2,87.9,54.9,20.3,17.8.

[0205] HRMS(ESI)m / z:[M+H] + C 30 H 24 NO + Calculated value: 414.1852; tested value: 414.1854.

[0206] Embodiment 19

[0207] This example relates to the synthesis of azabiaryl compound 53, the structure of which is as follows:

[0208]

[0209] The preparation process of this compound differs from that of Example 1 only in that: the alkynyl compound is compound 32, the aryl iodide is compound 14, no deprotection operation is required, the eluent for silica gel column chromatography is petroleum ether / ethyl acetate = 15 / 1, no deprotection operation is required, and the other operations are the same, and 89.4 mg of a cyan oily product is prepared with a yield of 45%.

[0210] The product was characterized and the results are as follows:

[0211] 1H NMR (400MHz, CDCl3) δ8.31(dd,J=4.4,2.0Hz,1H),7.81(m,2H),7.72(d,J=8.8Hz,1H),7.58–7.42(m,3H),7.07(dd,J=8 .0,4.3Hz,1H),7.02(s,1H),6.94(s,1H),6.44–6.35(m,2H),6.34–6.22(m,2H),3.46(s,3H),2.38(s,3H),2.28(s,3H).

[0212] 13 C NMR (101MHz, CDCl3) δ158.6,149.1,147.1,146.9,140.7,138.6,137.0,134.9,134.4,132.0,131.1,129.7, 128.1,127.9,127.8,127.0,126.7,126.3,125.6,120.9,119.6,116.0,113.3,94.8,87.4,55.0,21.6,21.1.

[0213] HRMS(ESI)m / z:[M+H] + C 30 H 24 NO + Calculated value: 414.1852; tested value: 414.1855.

[0214] Embodiment 20

[0215] This example relates to the synthesis of azabiaryl compound 54, the structure of which is as follows:

[0216]

[0217] The preparation process of this compound differs from that of Example 1 only in that the alkynyl compound is compound 33, no deprotection operation is required, the eluent for silica gel column chromatography is petroleum ether / ethyl acetate = 15 / 1, no deprotection operation is required, and the other operations are the same, and 96.7 mg of a yellow oily product is prepared with a yield of 45%.

[0218] The product was characterized and the results are as follows:

[0219] 1H NMR (400MHz, CDCl3) δ8.35 (dd, J=4.4, 1.6Hz, 1H), 7.91 (dd, J=8.0, 1.9Hz, 1H), 7.84 (dd, J=8.0,1.6Hz,1H),7.75(d,J=8.8Hz,1H),7.61(t,J=7.6Hz,1H),7.55(d,J=8.8Hz,1H),7. 49(dd,J=7.2,1.2Hz,1H),7.28–7.18(m,2H),7.18–7.13(m,2H),6.39(d,J=8.4Hz,1H),6 .14(dd,J=8.4,2.0Hz,1H),5.74(d,J=2.0Hz,1H),3.63(s,3H),3.55(s,3H),2.46(s,3H).

[0220] 13 C NMR (101MHz, CDCl3) δ149.3,148.6,148.0,147.1,146.8,140.7,138.7,135.0,134.3,131.1,129.6,128.1,127.8,127 .3,127.1,126.9,126.7,125.7,125.5,123.8,122.3,121.0,115.8,113.5,113.4,110.5,95.7,87.1,55.7,55.6,21.1.

[0221] HRMS(ESI)m / z:[M+H] + C 30 H 24 NO2 + Calculated value: 430.1802; tested value: 430.1806.

[0222] Embodiment 21

[0223] This example relates to the synthesis of azabiaryl compound 55, the structure of which is as follows:

[0224]

[0225] The preparation process of this compound differs from that of Example 1 only in that: the 10-bromobenzoquinoline analogue is compound 2, the added amount is 0.3 mmol (1.0 equiv.), the eluent for silica gel column chromatography is petroleum ether / ethyl acetate = 15 / 1, and the other operations are the same, and 51.8 mg of a cyan oily product is prepared with a yield of 70%.

[0226] The product was characterized and the results are as follows:

[0227] 1 H NMR (400MHz, CDCl3) δ8.60(d,J=2.4Hz,1H),8.05(d,J=2.4Hz,1H),7.85(dd,J=8.0,1.2Hz,1H),7.78(d,J=8.8Hz,1H),7 .63–7.57(m,2H),7.52–7.46(m,3H),7.32–7.27(m,2H),7.26–7.11(m,4H),6.46–6.34(m,4H),3.52(s,3H),2.46(s,3H).

[0228] 13 C NMR (101MHz, CDCl3) δ149.9,146.2,145.9,140.3,140.2,137.9,134.5,133.3,132.4,130.8,129.4,12 8.9,128.7,128.2,127.8,127.7,127.3,126.94,126.87,126.7,125.9,125.8,121.0,83.2,82.1,21.2.

[0229] HRMS(ESI)m / z:[M+H] + C 28 H 20 N + Calculated value: 370.1590; tested value: 370.1588.

[0230] Embodiment 22

[0231] This example relates to the synthesis of azabiaryl compound 56, the structure of which is as follows:

[0232]

[0233] The preparation process of this compound differs from that of Example 1 only in that: the 10-bromobenzoquinoline analog is compound 2, the addition amount is 0.3 mmol (1.0 equiv.), the alkynyl compound is compound 30, no deprotection operation is required, and the other operations are the same, and 90.3 mg of brown oily product is prepared with a yield of 64%.

[0234] The product was characterized and the results are as follows:

[0235] 1H NMR (400MHz, CDCl3) δ8.60(d,J=2.4Hz,1H),8.05(d,J=2.4Hz,1H),7.85(dd,J=8.0,1.2Hz,1H),7.78(d,J=8.8Hz,1H),7 .63–7.57(m,2H),7.52–7.46(m,3H),7.32–7.27(m,2H),7.26–7.11(m,4H),6.46–6.34(m,4H),3.52(s,3H),2.46(s,3H).

[0236] 13 C NMR (101MHz, CDCl3) δ158.8,149.2,146.1,145.9,140.6,138.9,137.8,134.4,133.3,132.4,132.2,131.1,129.6,1 28.9,128.6,128.0,127.7,127.2,127.0,126.9,126.7,125.9,125.6,122.5,115.8,113.4,95.8,87.3,55.0,21.2.

[0237] HRMS(ESI)m / z:[M+H] + C 35 H 26 NO + Calculated value: 476.2002; tested value: 476.2005.

[0238] Embodiment 23

[0239] This example relates to the synthesis of azabiaryl compound 57, the structure of which is as follows:

[0240]

[0241] The preparation process of this compound is different from that of Example 1 only in that: the 10-bromobenzoquinoline analog is compound 3, the added amount is 0.3 mmol (1.0 equiv.), the aryl iodide is compound 12, the eluent for silica gel column chromatography is petroleum ether / ethyl acetate = 30 / 1, and the other operations are the same, and 45.2 mg of a yellow solid product is prepared with a yield of 44%.

[0242] The product was characterized and the results are as follows:

[0243] 1H NMR (400MHz, CDCl3) δ8.34(d,J=8.0Hz,1H),8.01(d,J=4.4Hz,1H),7.91(dd,J=8.0,1.6Hz,1H),7.84(dd,J=9.2,4.8Hz,3H),7.76(d,J=8.4H z,1H),7.66(t,J=7.6Hz,1H),7.58–7.50(m,2H),7.48–7.43(m,1H),7.33(d,J=8.4Hz,1H),7.01(d,J=4.4Hz,1H),2.94(s,1H),2.62(s,3H).

[0244] 13 C NMR (101MHz, CDCl3) δ145.6,139.2,133.4,132.9(2C),130.6,130.3,128.7,127.3,127.2,127.1,126 .8,126.4(2C),125.9,125.6,125.4(2C),125.3,124.5,121.2,120.6,115.08,83.2,80.5,28.7,18.2.

[0245] HRMS(ESI)m / z:[M+H] + C 26 H 18 N + Calculated value: 343.1435; tested value: 343.1434.

[0246] Embodiment 24

[0247] This example relates to the synthesis of azabiaryl compound 58, the structure of which is as follows:

[0248]

[0249] The preparation process of this compound differs from that of Example 1 only in that: the 10-bromobenzoquinoline analog is compound 3, the alkynyl compound is compound 30, the eluent for silica gel column chromatography is petroleum ether / ethyl acetate = 15 / 1, no deprotection operation is required, and the other operations are the same, and 70.2 mg of a yellow oily product is prepared with a yield of 34%.

[0250] The product was characterized and the results are as follows:

[0251] 1H NMR (400MHz, CDCl3) δ8.19(d,J=4.4Hz,1H),7.88(dd,J=8.0,1.2Hz,1H),7.83(s,2H),7.62(t,J=7.6Hz,1H),7.49(dd,J=7.2,1 .2Hz,1H),7.26–7.14(m,3H),7.08–6.97(m,1H),6.53–6.43(m,2H),6.42–6.27(m,2H),3.60(s,3H),2.58(s,3H),2.45(s,3H).

[0252] 13 C NMR (101MHz, CDCl3) δ158.8,149.7,146.6,142.7,140.9,138.8,134.2,132.2(2C),131.1,130.1,127.82,1 27.79,127.2,126.9,126.7,126.2,125.5,122.3,122.2,121.5,115.9,113.4,95.6,87.3,55.1,21.2,19.2.

[0253] HRMS(ESI)m / z:[M+H] + C 30 H 24 NO + Calculated value: 414.1852; tested value: 414.1850.

[0254] Embodiment 25

[0255] This example relates to the synthesis of azabiaryl compound 59, the structure of which is as follows:

[0256]

[0257] The preparation process of this compound differs from that of Example 1 only in that: the 10-bromobenzoquinoline analog is compound 4, the alkynyl compound is compound 30, the eluent for silica gel column chromatography is petroleum ether / ethyl acetate = 15 / 1, no deprotection operation is required, and the other operations are the same, and 106.4 mg of a yellow oily product is prepared with a yield of 42%.

[0258] The product was characterized and the results are as follows:

[0259] 1H NMR (400MHz, CDCl3) δ8.35–8.24(m,1H),7.92–7.83(m,2H),7.56–7.51(m,1H),7.48(d,J=5.6Hz,2H),7.40(d,J=7.2Hz,2H ),7.27–7.22(m,2H),7.18–7.13(m,2H),6.99(d,J=8.8Hz,2H),6.49–6.39(m,4H),3.81(s,3H),3.57(s,3H),2.44(s,3H).

[0260] 13 C NMR (101MHz, CDCl3) δ159.1,158.8,149.7,146.8,146.3,140.8,139.5,138.8,135.0,133.7,133.1,132.2,131.1,130. 9,130.1,127.4,126.8,126.8,126.3,125.5,122.2,121.3,115.9,113.8,113.44,113.36,95.6,87.3,55.4,55.1,21.2.

[0261] HRMS(ESI)m / z:[M+H] + C 36 H 28 NO2 + Calculated value: 506.2115; tested value: 506.2115.

[0262] Embodiment 26

[0263] This example relates to the synthesis of azabiaryl compound 60, the structure of which is as follows:

[0264]

[0265] The preparation process of the compound is different from that of Example 1 only in that the 10-bromobenzoquinoline analog is compound 5, the alkynyl compound is compound 30, the eluent for silica gel column chromatography is petroleum ether / ethyl acetate = 15 / 1, no deprotection operation is required, and the other operations are the same, and 103.3 mg of a yellow oily product is prepared with a yield of 46%.

[0266] The product was characterized and the results are as follows:

[0267] 1H NMR (500MHz, CDCl3) δ8.71–8.57(m,3H),8.41(d,J=8.0Hz,1H),8.25(dd,J=4.4,1.6Hz,1H),7.72–7.54(m,3H),7.51(dd,J=7 .2,1.2Hz,1H),7.28–7.20(m,3H),7.17–7.11(m,1H),6.34(d,J=8.8Hz,2H),6.28(d,J=8.8Hz,2H),3.54(s,3H),2.43(s,3H).

[0268] 13 C NMR (126MHz, CDCl3) δ158.7,149.8,146.9,146.9,141.3,138.9,132.1,132.1,131.8,130.2,130.0,129.6,129.2,127.7 2,127.66,127.4,127.3,126.6,125.4,124.6,123.8,123.0,122.2,121.9,121.4,115.7,113.2,95.7,87.2,55.0,21.2.

[0269] HRMS(ESI)m / z:[M+H] + C 33 H 24 NO + Calculated value: 450.1851; tested value: 450.1852.

[0270] Embodiment 27

[0271] This example relates to the synthesis of azabiaryl compound 61, the structure of which is as follows:

[0272]

[0273] The preparation process of this compound differs from that of Example 1 only in that the aryl bromide is compound 21, the eluent for silica gel column chromatography is petroleum ether / ethyl acetate = 15 / 1, and the other operations are the same, to obtain 131.4 mg of a colorless oily product with a yield of 52%.

[0274] The product was characterized and the results are as follows:

[0275] 1H NMR (400MHz, CDCl3) δ8.30-8.23(m,1H),8.00-7.95(m,1H),7.87(dd,J=8.0,1.4Hz,1H),7.7 6(d,J=8.8Hz,1H),7.64–7.55(m,2H),7.42(d,J=7.2Hz,1H),7.28–7.19(m,2H),7.19–7.13( m,4H),7.02–6.97(m,2H),5.27(d,J=2.4Hz,2H),3.74(q,J=7.2Hz,1H),2.50(d,J=5.4Hz,1H ),2.36(dd,J=7.2Hz,2H),1.79-1.69(m,1H),1.46(dd,J=7.2,2.0Hz,3H),0.82–0.79(m,6H).

[0276] 13 C NMR (101MHz, CDCl3) δ174.5,150.2,147.1,146.7,140.5,139.5,137.8,,137.7,135.0,134.4,130.7,129.5,129.2,128. 3,128.1,127.3,127.2,127.0,126.8,125.8,124.9,124.8,121.0,120.2,84.3,80.2,65.3,45.2,45.0,30.2,22.4,18.5.

[0277] HRMS(ESI)m / z:[M+H] + C 35 H 32 NO2 + Calculated value: 498.2428; tested value: 498.2436.

[0278] Embodiment 28

[0279] This example relates to the synthesis of azabiaryl compound 62, the structure of which is as follows:

[0280]

[0281] The preparation process of this compound differs from that of Example 1 only in that the aryl bromide is compound 22, the eluent for silica gel column chromatography is petroleum ether / ethyl acetate = 2 / 1, and the other operations are the same, to obtain 162.1 mg of a white solid product with a yield of 56%.

[0282] The product was characterized and the results are as follows:

[0283] 1H NMR(400MHz, CDCl3)δ8.45–8.36(m,1H),8.07(dd,J=8.0,1.8Hz,1H),7.98–7.93(m,2H),7.85(d,J=8.8Hz ,1H),7.75–7.66(m,2H),7.48(d,J=8.0Hz,1H),7.35–7.28(m,1H),7.19(dd,J=8.0,2.4Hz,1H),5.61(dd, J=5.2,2.4Hz,1H),4.69(dd,J=8.02.4Hz,1H),4.64–4.55(m,1H),4.54–4.46(m,1H),4.42–4.35(m,2H),4 .30–4.22(m,1H),2.82(s,3H),2.71(d,J=1.6Hz,1H),1.55(s,3H),1.51(s,3H),1.38(s,3H),1.35(s,3H).

[0284] 13 C NMR (101MHz, CDCl3) δ167.8,167.7,154.1,147.2,146.5,142.0,139.5,135.1,(134.4,130.2),130.1,129.2,128.3,128.1,127.7,127.0,12 6.8,125.8,125.7,122.9,121.0,109.7,108.8,96.3,84.2,81.5,71.2 ,70.7,70.5,66.2,63.9,63.8,26.01,25.95,24.9,24.5,19.24,19.19.

[0285] HRMS(ESI)m / z:[M+H] + C 35 H 34 NO7 + Calculated value: 580.2330; tested value: 508.2328.

[0286] Embodiment 29

[0287] This example relates to the synthesis of azabiaryl compound 63, the structure of which is as follows:

[0288]

[0289] The preparation process of this compound differs from that of Example 1 only in that the aryl bromide is compound 22, the alkynyl compound is compound 30, the eluent for silica gel column chromatography is petroleum ether / ethyl acetate = 5 / 1, no deprotection operation is required, and the other operations are the same, and 202.4 mg of a white solid product is prepared with a yield of 61%.

[0290] The product was characterized and the results are as follows:

[0291] 1 H NMR (400MHz, CDCl3) δ8.35 (dd, J=4.4, 1.6Hz, 1H), 8.01–7.86 (m, 3H), 7.79 (d, J=8.8Hz, 1H), 7.71–7.5 4(m,2H),7.42(d,J=7.2Hz,1H),7.22(d,J=8.0Hz,2H),6.51–6.44(m,2H),6.39–6.33(m,2H),5.53(dd ,J=5.2,2.4Hz,1H),4.61(dd,J=7.6,2.4Hz,1H),4.56–4.49(m,1H),4.46–4.38(m,1H),4.35–4.28(m, 2H),4.22–4.16(m,1H),3.61(s,3H),2.75(s,3H),1.49(s,3H),1.44(s,3H),1.31(s,3H),1.28(s,3H).

[0292] 13 C NMR(101MHz, CDCl3)δ(167.9,167.8),159.0,153.4,147.2,146.6,140.6,140.5 ,139.9,135.0,134.3,132.2,130.5,129.6,129.4,128.2,128.0,127.6,127.5,1 27.0,126.7,125.7,125.4,124.4,121.0,115.3,113.3,109.6,108.7,96.7,96.3,86.8,71.2,70.7,70.5,66.2,63.8,55.0,26.02,25.96,24.9,24.5,19.4,19.3.

[0293] HRMS(ESI)m / z:[M+H] + C 42 H 40 NO8 + Calculated value: 686.2748; tested value: 686.2753.

[0294] Embodiment 30

[0295] This example relates to the synthesis of azabiaryl compound 64, the structure of which is as follows:

[0296]

[0297] The preparation process of this compound differs from that of Example 1 only in that the alkynyl compound is compound 34, the eluent for silica gel column chromatography is petroleum ether / ethyl acetate = 4 / 1, and the other operations are the same, to obtain 68.3 mg of a yellow solid product with a yield of 39%.

[0298] The product was characterized and the results are as follows:

[0299] 1 H NMR (400MHz, CDCl3) δ8.43–8.31(m,1H),8.03(d,J=8.0Hz,1H),7.95(d,J=2.4H z,1H),7.86(dd,J=8.0,1.6Hz,1H),7.83–7.75(m,2H),7.67–7.58(m,2H),7.50– 7.37(m,3H),7.30–7.20(m,4H),7.18–7.13(m,2H),6.89(d,J=8.4Hz,1H),5.09 (s,2H),3.33(s,2H),3.24(t,J=7.2Hz,2H),2.35(s,3H),2.00(t,J=7.2Hz,2H).

[0300] 13 C NMR (101MHz, CDCl3) δ190.8,170.8,160.4,146.9,140.5,140.4,139.3,136.3,135.5,134.4,132.8,132.3,131.0,129.4,129.2,128.4 ,128.0,127.8,127.5,127.2,127.1,127.0,126.8,125.7,125.6,125.0,122.0,121.1,121.0,91.2,80.6,73.6,62.5,39.8,21.2,19.4.

[0301] HRMS((ESI))m / z:[M+H] + C 40 H 30 NO4 + Calculated value: 588.2169; Test value: 588.2169.

[0302] Embodiment 31

[0303] This example relates to the synthesis of azaspiricene compound 65, the structure of which is as follows:

[0304]

[0305] The specific operations are as follows:

[0306] Under N2 protection, PtCl4 (6.7 mg, 0.02 mmol, 10 mol%), azabiaryl compound 35 (0.2 mmol, 1.0 equiv.) and ultra-dry DCE (1.0 mL) were added to a dry sealed tube. The test tube was tightly sealed and reacted at 120°C for 16 hours. After the reaction was completed (monitored by thin layer chromatography), the mixture was cooled to room temperature. It was extracted with 2N sodium hydroxide solution and ethyl acetate, the organic phases were combined, and the crude product obtained by concentration in vacuo was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 10 / 1) to obtain 12.9 mg of a brown solid product with a yield of 22%.

[0307] The product was characterized and the results are as follows:

[0308] 1 H NMR (400MHz, CDCl3) δ8.61(dd,J=4.4,1.6Hz,1H),8.20(dd,J=8.0,1.6Hz,1H),8.10(d,J=8.8Hz,1H),7.95–7.88( m,3H),7.86–7.76(m,3H),7.41(dd,J=8.4,4.0Hz,1H),7.30(d,J=6.8Hz,1H),7.07(t,J=8.4Hz,1H),2.75(s,3H).

[0309] 13 C NMR (101MHz, CDCl3) δ146.8,135.6,134.2,133.1,132.2,131.6,131.2,129.0,12 8.7,128.0,127.5,127.3,126.6,126.5,126.1,125.4,124.3,122.7,121.7,20.2

[0310] HRMS((ESI))m / z:[M+H] + C 22 H 16 N + Calculated value: 294.1277; tested value: 294.1276.

[0311] Embodiment 32

[0312] This example relates to the synthesis of azaspiricene compound 66, the structure of which is as follows:

[0313]

[0314] The preparation process of this compound differs from that of Example 31 only in that the azabiaryl compound is compound 40, the eluent for silica gel column chromatography is petroleum ether / ethyl acetate = 10 / 1, and the other operations are the same, to obtain 17.2 mg of a yellow oily product with a yield of 26%.

[0315] The product was characterized and the results are as follows:

[0316] 1 H NMR (400MHz, CDCl3) δ8.59(dd,J=4.0,1.6Hz,1H),8.15(d,J=6.4Hz,1H),8.03(d,J=8.8Hz,1H),7.86(d,J=3.2Hz ,1H),7.84(d,J=2.8Hz,1H),7.82–7.74(m,4H),7.38(dd,J=8.0,4.4Hz,1H),7.10(d,J=9.1Hz,1H),2.75(s,3H).

[0317] 13 C NMR (101MHz, CDCl3) δ146.9,135.8,134.4,132.7,131.9,131.88,130.0,129.81 ,129.75,128.6,127.5,126.8,126.6,126.4,126.3,124.1,124.0,121.8,16.1.

[0318] HRMS((ESI))m / z:[M+H] + C 22 H 15 C1N + Calculated value: 328.0888; tested value: 328.0889.

[0319] Embodiment 33

[0320] This example relates to the synthesis of azaspiricene compound 67, the structure of which is as follows:

[0321]

[0322] The preparation process of this compound differs from that of Example 31 only in that the azabiaryl compound is compound 42, the eluent for silica gel column chromatography is petroleum ether / ethyl acetate = 10 / 1, and the other operations are the same, to obtain 30.2 mg of a yellow solid product with a yield of 46%.

[0323] The product was characterized and the results are as follows:

[0324] 1 H NMR(400MHz, CDCl3)δ8.75–8.68(m,3H),8.25(d,J=7.6Hz,1H),8.07–7.98(m,3H),7.95–7.88(m, 3H),7.85(d,J=9.2Hz,1H),7.70–7.58(m,2H),7.51(d,J=9.2Hz,1H),7.44(dd,J=8.4,3.6Hz,1H).

[0325] 13 C NMR (101MHz, CDCl3) δ147.1,135.9,134.4,132.32,132.27,130.2,129.9,129.3,129.2,128.9,1 28.0,127.6,127.4,126.64,126.55,126.39,126.32,126.0,125.8,123.5,123.0,122.8,121.5.

[0326] HRMS((ESI))m / z:[M+H] + C 25 H 16 N + Calculated value: 330.1277; Test value: 330.1277.

[0327] Embodiment 34

[0328] This example relates to the synthesis of azaspiroene compound 68, the structure of which is as follows:

[0329]

[0330] The preparation process of this compound differs from that of Example 31 only in that the azabiaryl compound is compound 62, the eluent for silica gel column chromatography is petroleum ether / ethyl acetate = 2 / 1, and the other operations are the same, to obtain 35.5 mg of a white solid product with a yield of 26%.

[0331] The product was characterized and the results are as follows:

[0332] 1H NMR (400MHz, CDCl3) δ8.59–8.45(m,1H),8.14–8.09(m,2H),7.82(d,J=8.8Hz,1 H),7.77–7.60(m,5H),7.49(d,J=9.2Hz,1H),7.30(dd,J=8.0,4.0Hz,1H),5.49 (d,J=4.8Hz,1H),4.59–4.45(m,2H),4.39(dd,J=11.6,7.6Hz,1H),4.30–4.22( m,2H),4.18–4.10(m,1H),2.91(s,3H),1.39(s,6H),1.23(s,3H),1.20(s,3H).

[0333] 13 C NMR (101MHz, CDCl3) δ168.7,146.8,135.6,134.2,133.0,132.7,131.8,128.44,128.36,127.9,127.33,127.29,126. 6,126.2,125.9,124.5,123.2,121.7,109.5,108.7,96.2,71.1,70.6,70.4,66.2,64.0,26.0,25.9,24.9,24.3,16.5.

[0334] HRMS(ESI)m / z:[M+H] + C 35 H 34 NO7 + Calculated value: 580.2330; Test value: 508.2329.

[0335] Embodiment 35

[0336] This example involves the synthesis of azaspiricene compound 69 and compound 77, the structures of which are as follows:

[0337]

[0338] The specific operations are as follows:

[0339] In a dry round-bottom flask, azabiaryl compound 49 (0.2 mmol) was added to ultra-dry DCM (4.0 mL), and HOTf (0.40 mmol, 2.0 equiv.) was added at 0°C. The resulting reaction mixture was heated to room temperature and stirred for 3 hours. After quenching with 2N aqueous sodium hydroxide solution, water was added and the aqueous phase was extracted twice with dichloromethane. The combined organic phase was dried (Na2SO4), concentrated in vacuo, and the residue was purified by column chromatography (eluent: petroleum ether / dichloromethane = 2 / 3) to give 33.5 mg of yellow solid compound 69 with a yield of 42% and 34.2 mg of yellow solid compound 77 with a yield of 43%.

[0340] The product compound 69 was characterized, and the characterization results are as follows:

[0341] 1 H NMR (400MHz, CDCl3) δ8.58(dd,J=4.4,1.6Hz,1H),8.11(dd,J=8.0,1.6Hz,1H),7.97(s,1H),7.89(d,J=8.4Hz,1H),7.85–7.78(m,2H),7.73(d,J=8.4H z,1H),7.66(d,J=8.4Hz,1H),7.41(d,J=8.0Hz,2H),7.34(dd,J=8.0,4.0H z,1H),7.26(d,J=6.8Hz,1H),7.05–6.93(m,3H),3.79(s,3H),2.69(s,3H).

[0342] 13 C NMR (101MHz, CDCl3) δ159.0,146.9,136.8,135.7,133.9,133.6,133.2,131.7,131.2,130.8 ,128.8,128.7,127.4,127.2,127.0,126.5,126.2,125.9,124.8,122.7,121.6,55.3,20.1..

[0343] HRMS(ESI)m / z:[M+H] + C 29 H 22 ON + Calculated value: 400.1696; tested value: 400.1695.

[0344] The product compound 77 was characterized, and the characterization results are as follows:

[0345] 1H NMR (400MHz, CDCl3) δ8.86(d,J=8.8Hz,1H),8.56(d,J=8.4Hz,1H),8.30(dd,J=4.4,1.6Hz,1H),8.08(s,1H),7.99(d,J=8.8Hz,1H),7.93(dd,J=8.0, 1.6Hz,1H),7.88(d,J=8.4Hz,1H),7.69(d,J=8.4Hz,1H),7.50(t,J=8.0Hz ,1H),7.42(d,J=7.2Hz,1H),7.09–7.00(m,1H),3.59(s,3H),2.77(s,3H).

[0346] 13 C NMR (101MHz, CDCl3) δ157.4,147.0,145.3,139.4,139.1,134.8,134.3,133.3,132.2,131.4,129.22,128 .53,127.8,127.6,126.9,126.6,126.32,126.30,126.1,126.0,125.9,123.5,121.1,119.8,55.2,19.9.

[0347] Note: C and H atoms in red are not visible in NMR.

[0348] HRMS(ESI)m / z:[M+H] + C 29 H 22 NO + Calculated value: 400.1696; tested value: 400.1693.

[0349] Embodiment 36

[0350] This example involves the synthesis of azaspiricene compound 70 and compound 78, the structures of which are as follows:

[0351]

[0352] The preparation process of this compound differs from that of Example 36 only in that the nitrogen biaryl compound is compound 52, and the other operations are the same, to prepare 25.6 mg of brown solid compound 70 with a yield of 31% and 37.3 mg of brown solid compound 78 with a yield of 45%.

[0353] The product compound 70 was characterized, and the characterization results are as follows:

[0354] 1H NMR (400MHz, CDCl3) δ8.73(dd,J=4.4,1.6Hz,1H),8.30(d,J=8.0Hz,1H),8.13(s,1H),8.01(d,J=8.4Hz,1H),7.96(d,J=8.4Hz,1H),7.88(d,J=8.4Hz,1H ),7.82(d,J=8.4Hz,1H),7.78(d,J=8.4Hz,1H),7.59–7.47(m,3H),7.10(d, J=8.4Hz,1H),7.07(d,J=8.4Hz,1H),3.94(s,3H),2.71(s,3H),2.54(s,3H).

[0355] 13 C NMR (101MHz, CDCl3) δ159.0,146.6,136.7,134.1,134.0,133.8,131.7,131.1,130.7,130.4,129.2 ,128.8,127.9,127.5,127.2,126.6,126.13,126.05,125.6,124.9,121.5,113.7,55.4,20.9,15.2.

[0356] HRMS(ESI)m / z:[M+H] + C 30 H 24 NO + Calculated value: 414.1852; Test value: 414.1852.

[0357] The product compound 78 was characterized, and the characterization results are as follows:

[0358] 1 H NMR (400MHz, CDCl3) δ8.80(d,J=8.8Hz,1H),8.43(d,J=8.4Hz,1H),8.28(m,1H),8.10(d,J=2.0Hz,1H),7.93(d,J=8.8Hz,1H),7.88(dd,J=8.0,1. 6Hz,1H),7.82(d,J=8.8Hz,1H),7.63(d,J=8.8Hz,1H),7.39(d,J=8.8Hz, 1H),7.00(dd,J=8.0,4.0Hz,1H),3.57(s,3H),2.65(s,3H),2.47(s,3H).

[0359] 13C NMR (101MHz, CDCl3) δ157.3,146.9,145.3,139.4,139.3,134.5,134.2,133.1,132.4,132.1,131.6,1 29.0,128.5,127.7,127.6,127.0,126.6,126.2,126.1,125.5,123.4,120.4,119.7,55.2,20.8,15.2.

[0360] Note: C and H atoms in red are not visible in NMR.

[0361] HRMS(ESI)m / z:[M+H] + C 30 H 24 NO + Calculated value: 414.1852; Test value: 414.1854.

[0362] Embodiment 37

[0363] This example involves the synthesis of azaspiricene compound 71 and compound 79, the structures of which are as follows:

[0364]

[0365] The preparation process of this compound differs from that of Example 36 only in that the nitrogen biaryl compound is compound 53, and the other operations are the same, to prepare 42.3 mg of yellow solid compound 71 with a yield of 49% and 30.5 mg of yellow solid compound 79 with a yield of 37%.

[0366] The product compound 71 was characterized, and the characterization results are as follows:

[0367] 1 H NMR (400MHz, CDCl3) δ8.65–8.48 (m, 1H), 8.10 (dd, J = 8.0, 2.0Hz, 1H), 7.92 (s, 1H),7.87(dd,J=8.4,2.4Hz,1H),7.77(dd,J=8.4,2.4Hz,1H),7.69(dd,J=8.4 ,2.4Hz,1H),7.64–7.55(m,2H),7.39(dd,J=8.4,2.4Hz,2H),7.36–7.28(m,1H ),7.11(s,1H),6.94(d,J=8.0Hz,2H),3.77(s,3H),2.65(s,3H),2.16(s,3H).

[0368] 13C NMR (101MHz, CDCl3) δ159.0,146.6,135.9,135.8,133.9,133.7,133.0,132.1,131.7,131.4,130.9,1 29.5,129.0,128.4,128.3,127.3,127.1,126.5,126.1,125.8,124.7,121.5,113.7,55.3,21.7,20.0.

[0369] HRMS(ESI)m / z:[M+H] + C 30 H 24 NO + Calculated value: 414.1852; tested value: 414.1856.

[0370] The product compound 79 was characterized, and the characterization results are as follows:

[0371] 1 HNMR (400MHz, CDCl3) δ8.83(d,J=8.8Hz,1H),8.32(s,1H),8.28(dd,J=4.4,1.6Hz,1H),8.02(s,1H),7.93(d,J=8.8Hz,1H),7.88(dd,J=8.0 ,1.6Hz,1H),7.83(d,J=8.4Hz,1H),7.65(d,J=8.8Hz,1H),7.24(s,1H),7.01(dd,J=8.0,4.4Hz,1H),3.57(s,3H),2.71(s,3H),2.52(s,3H).

[0372] 13 C NMR (101MHz, CDCl3) δ157.3,146.9,145.2,139.21,138.4,135.4,134.6,134.4,133.3,131.9,129.8,129.5 ,129.4,128.5,127.5,127.0,126.6,126.24,126.15,126.1,126.0,123.7,120.7,119.7,55.2,22.2,19.8.

[0373] Note: C and H atoms in red are not visible in NMR.

[0374] HRMS(ESI)m / z:[M+H] + C 30 H 24 NO +Calculated value: 414.1852; tested value: 414.1853.

[0375] Embodiment 38

[0376] This example involves the synthesis of azaspiricene compound 72 and compound 80, the structures of which are as follows:

[0377]

[0378] The preparation process of this compound differs from that of Example 36 only in that the nitrogen biaryl compound is compound 50, the eluent for silica gel column chromatography is dichloromethane / ethyl acetate = 40 / 1, and the other operations are the same, to prepare 21.7 mg of yellow solid compound 72 with a yield of 25% and 26.7 mg of yellow solid compound 80 with a yield of 31%.

[0379] The product compound 72 was characterized, and the characterization results are as follows:

[0380] 1 H NMR(400MHz, CDCl3)δ9.05(s,1H),8.68(dd,J=4.0,1.6Hz,1H),8.19(dd,J=8.0,2.0Hz,1H),7.93–7.85(m,4H),7.79( d,J=8.8Hz,1H),7.43(dd,J=8.0,4.4Hz,1H),7.38(d,J=8.0Hz,2H),6.99(d,J=8.0Hz,2H),3.84(s,3H),2.72(s,3H).

[0381] 13 C NMR (101MHz, CDCl3) δ159.6,150.7,148.0,146.6,145.9,142.5,136.1,136.0,134.4132.4,131.41 ,131.37,127.7,127.4,127.3,127.1,126.9,126.6,124.5,123.7,123.0,122.4,113.9,55.4,15.4.

[0382] HRMS(ESI)m / z:[M+H] + C 28 H 20 ClN2O + Calculated value: 435.1259; tested value: 435.1256.

[0383] The product compound 80 was characterized, and the characterization results are as follows:

[0384] 1HNMR(400MHz, CDCl3)δ9.71(s,1H),8.89(d,J=8.8Hz,1H),8.32(dd,J=4.4,1.6Hz,1H),8.11(d,J=8.8Hz,1H),8.01–7.9 6(m,2H),7.93(d,J=8.4Hz,1H),7.78(d,J=8.4Hz,1H),7.10(dd,J=8.0,4.4Hz,1H),3.61(d,J=1.2Hz,3H),2.80(s,3H).

[0385] 13 C NMR (101MHz, CDCl3) δ158.1,147.6,147.2,145.3,144.7,138.0,137.2,134.7,133.9,131.3 ,128.6,128.2,127.1,127.0,126.9,126.4,125.8,124.0,123.0,122.2,120.3,55.3,15.5.

[0386] Note: C and H atoms in red are not visible in NMR.

[0387] HRMS(ESI)m / z:[M+H] + C 28 H 20 ClN2O + Calculated value: 435.1259; tested value: 435.1256.

[0388] Embodiment 39

[0389] This example involves the synthesis of azaspiricene compound 73 and compound 81, whose structures are as follows:

[0390]

[0391] The preparation process of this compound differs from that of Example 36 only in that the nitrogen biaryl compound is compound 51, and the other operations are the same, to prepare 31.9 mg of yellow solid compound 73 with a yield of 36% and 24.8 mg of yellow solid compound 81 with a yield of 28%.

[0392] The product compound 73 was characterized, and the characterization results are as follows:

[0393] 1H NMR(400MHz, CDCl3)δ9.02(m,1H),8.37(s,1H),8.32(dd,J=8.0,1.8Hz,1H),8.19–8.14(m,1H),8.07(d,J=8.8Hz,1H),7.94–7.87(m,2H) ,7.78–7.73(m,1H),7.68(d,J=8.8Hz,1H),7.63–7.56(m,1H),7.52–7.46(m,2H),7.41–7.34(m,2H),7.04(d,J=8.8Hz,2H),3.87(s,3H).

[0394] 13 C NMR (101MHz, CDCl3) δ159.2,146.6,145.7,139.7,138.8,137.0,135.9,135.1,134.6,134.2,133.8,132.4 ,131.8,128.8,127.6,127.5,127.0,126.6,126.5,125.4,123.7,121.8,121.4,121.3,121.1,113.9,55.4.

[0395] HRMS(ESI)m / z:[M+H] + C 30 H 20 NOS + Calculated value: 442.1260; tested value: 442.1258.

[0396] The product compound 81 was characterized, and the characterization results are as follows:

[0397] 1 HNMR(400MHz, CDCl3)δ8.31(s,1H),8.27(dd,J=4.4,1.8Hz,1H),8.25(d,J=8.4Hz,1H),8.23–8.20(m,1H),7.95(dd,J=8.0,1.8Hz,1H),7.93 –7.91(m,1H),7.91–7.89(m,1H),7.85(d,J=8.4Hz,1H),7.71(d,J=8.4Hz,1H),7.45–7.42(m,2H),7.05(dd,J=8.0,4.4Hz,2H),3.61(s,3H).

[0398] 13C NMR (101MHz, CDCl3) δ157.5,146.8,144.5,139.59,139.57,138.8,136.6,136.2,134.7,133.8,133.7,1 30.1,128.7,127.9,127.2,127.0,126.9,126.5,126.4,125.6,124.7,123.9,122.9,121.9,119.9,55.3.

[0399] Note: C and H atoms in red are not visible in NMR.

[0400] HRMS(ESI)m / z:[M+H] + C 30 H 20 NOS + Calculated value: 442.1260; tested value: 442.1259.

[0401] Embodiment 40

[0402] This example involves the synthesis of azaspiricene compound 74 and compound 82, the structures of which are as follows:

[0403]

[0404] The preparation process of this compound differs from that of Example 36 only in that the azabiaryl compound is compound 54, and the other operations are the same, to prepare 38.3 mg of yellow solid compound 74 with a yield of 45% and 43.6 mg of yellow solid compound 82 with a yield of 52%.

[0405] The product compound 74 was characterized, and the characterization results are as follows:

[0406] 1 H NMR (400MHz, CDCl3) δ8.70–8.60(m,1H),8.23(d,J=8.0Hz,1H),8.03(s,1H),7.94(d,J=8.8Hz,1H),7.90(d,J=8.4Hz,1H),7.86–7.78(m,2H),7.72(d ,J=8.4Hz,1H),7.43(dd,J=8.0,4.0Hz,1H),7.31(d,J=6.8Hz,1H),7.11–7 .01(m,3H),6.97(d,J=8.0Hz,1H),3.92(s,3H),3.82(s,3H),2.74(s,3H).

[0407] 13C NMR (101MHz, CDCl3) δ148.6,148.5,146.7,136.9,134.1,134.0,133.4,131.4,130.9,130.8,128.7,127.6 ,127.5,127.3,126.6,126.2,126.0,124.9,123.0,122.8,121.7,114.0,111.1,56.02,55.98,29.7,20.1.

[0408] HRMS(ESI)m / z:[M+H] + C 30 H 24 NO2 + Calculated value: 430.1802; tested value: 430.1805.

[0409] The product compound 82 was characterized, and the characterization results are as follows:

[0410] 1 H NMR (400MHz, CDCl3) δ8.86(d,J=8.4Hz,1H),8.56(d,J=8.4Hz,1H),8.30(dd,J=4.4,1.6Hz,1H),8.12(s,1H),7.98(d,J=8.4Hz,1H),7.93(dd,J=8.0,1. 6Hz,1H),7.87(d,J=8.4Hz,1H),7.69(d,J=8.4Hz,1H),7.50(dd,J=8.4,7.2 Hz,1H),7.42(m,1H),7.05(dd,J=8.0,4.0Hz,1H),3.68(s,3H),2.78(s,3H).

[0411] 13 C NMR (101MHz, CDCl3) δ146.8,146.8,145.2,139.2,134.8,134.4,133.2,132.3,131.3,129.3,127.9,12 7.3,127.1,126.5,126.3,126.2,126.1,126.0,125.9,123.7,121.1,119.9,119.9,111.4,55.9,19.9.

[0412] Note: C and H atoms in red are not visible in NMR.

[0413] HRMS(ESI)m / z:[M+H] + C 30 H 24 NO2+ Calculated value: 430.1803; tested value: 430.1801.

[0414] Embodiment 41

[0415] This example involves the synthesis of azaspiricene compound 75 and compound 83, the structures of which are as follows:

[0416]

[0417] The preparation process of this compound differs from that of Example 36 only in that the azabiaryl compound is compound 56, and the other operations are the same, to prepare 24.9 mg of yellow solid compound 75 with a yield of 53% and 20.1 mg of yellow solid compound 83 with a yield of 43%.

[0418] The product compound 75 was characterized, and the characterization results are as follows:

[0419] 1 H NMR (400MHz, CDCl3) δ8.94(s,1H),8.41(s,1H),8.03(s,1H),7.97–7.87(m,4H),7.75–7.68(m,3H),7.49–7.43(m,4H),7. 38(d,J=7.6Hz,2H),7.32(d,J=7.2Hz,1H),7.08(dd,J=8.8,6.0Hz,1H),7.01(d,J=8.8Hz,2H),3.85(s,3H),2.74(s,3H).

[0420] 13 C NMR (101MHz, CDCl3) δ159.1,145.6,136.8,134.2,134.1,133.6,133.5,131.7,131.5,131.1,130.7 ,129.2,128.7,128.3,128.0,127.6,127.2,126.6,126.3,126.0,125.1,123.1,113.8,55.4,20.1.

[0421] HRMS(ESI)m / z:[M+H] + C 35 H 26 NO + Calculated value: 476.2009; Test value: 476.2009.

[0422] The product compound 83 was characterized, and the characterization results are as follows:

[0423] 1H NMR (400MHz, CDCl3) δ8.94(d,J=8.0Hz,1H),8.58(d,J=8.4Hz,1H),8.50(s,1H ),8.26(s,1H),8.18(s,1H),8.03(d,J=8.4Hz,1H),7.98(d,J=8.0Hz,1H),7.8 1(d,J=8.0Hz,1H),7.54(d,J=7.4Hz,1H),7.51(d,J=2.0Hz,1H),7.49(d,J=1. 2Hz,1H),7.47–7.42(m,3H),7.37(t,J=8.0Hz,1H),3.55(s,3H),2.79(s,3H).

[0424] 13 C NMR (101MHz, CDCl3) δ157.6,145.9,144.4,139.4,139.1,138.1,134.8,133.3,132.4,132.3,131.5,131.4,129.3 ,129.0,127.89,127.86,127.4,127.3,126.44,126.38,126.3,126.2,126.10,125.98,123.6,121.2,29.7,20.0.

[0425] Note: C and H atoms in red are not visible in NMR.

[0426] HRMS(ESI)m / z:[M+H] + C 35 H 26 NO + Calculated value: 476.2009; tested value: 476.2015.

[0427] Embodiment 42

[0428] This example involves the synthesis of azaspiricene compound 76 and compound 84, the structures of which are as follows:

[0429]

[0430] The preparation process of this compound differs from that of Example 36 only in that the azabiaryl compound is compound 59, and the other operations are the same, to prepare 20.1 mg of yellow solid compound 76 with a yield of 40% and 14.1 mg of yellow solid compound 84 with a yield of 28%.

[0431] The product compound 76 was characterized, and the characterization results are as follows:

[0432] 1H NMR (400MHz, CDCl3) δ8.67(s,1H),8.29(s,1H),8.03(s,1H),7.87(d,J=8.8Hz,1H),7.84–7.74(m,3H),7.49–7. 38(m,5H),7.32(d,J=6.2Hz,1H),7.12–7.05(m,1H),7.02–6.93(m,4H),3.84(s,3H),3.83(s,3H),2.75(s,3H).

[0433] 13 C NMR (101MHz, CDCl3) δ159.2,159.0,146.9,146.5,138.8,136.6,135.5,133.6,133.3,133.0,132.6,131.6,131.5,131.2 ,130.9,130.8,129.1,128.7,128.2,127.3,126.6,126.3,125.9,124.9,124.4,122.8,121.9,113.8,113.7,55.4,20.2.

[0434] HRMS(ESI)m / z:[M+H] + C 36 H 28 NO2 + Calculated value: 506.2115; tested value: 506.2113.

[0435] The product compound 84 was characterized, and the characterization results are as follows:

[0436] 1 H NMR (400MHz, CDCl3) δ8.82(d,J=9.0Hz,1H),8.54(d,J=8.4Hz,1H),8.38(d,J=4.4Hz,1H),8.12(s,1H),8.04(t,J=8.2Hz,2H),7.66(s,1H),7.52(d,J =2.0Hz,1H),7.50(d,J=7.6Hz,2H),7.43(d,J=6.8Hz,1H),7.13(dd,J=8.0 ,4.4Hz,1H),7.05(d,J=8.8Hz,2H),3.88(s,3H),3.63(s,3H),2.79(s,3H).

[0437] 13C NMR (101MHz, CDCl3) δ159.3,157.4,147.1,145.1,139.8,139.2,138.5,134.7,134.1,132.7,132.3,131.9,131.52,131.49 ,129.1,128.6,128.5,127.9,126.5,126.23,126.15,125.94,125.87,124.7,123.1,121.1,120.0,113.9,55.4,55.2,19.9.

[0438] Note: C and H atoms in red are not visible in NMR.

[0439] HRMS(ESI)m / z:[M+H] + C 36 H 28 NO2 + Calculated value: 506.2115; tested value: 506.2113.

[0440] The above-described embodiments are only preferred embodiments for fully illustrating the present invention, and the protection scope of the present invention is not limited thereto. Equivalent substitutions or changes made by those skilled in the art based on the present invention are within the protection scope of the present invention. The protection scope of the present invention shall be subject to the claims.

Claims

1. An azabiaryl compound, characterized in that: The azabiaryl compound has the following general structural formula: Among them, R 1 The substitution site is any one of 2-9, selected from hydrogen, alkyl, substituted aryl; or R 1 Any two sites adjacent to the azabiaryl group are cyclized to form a benzene ring; Ar is R 2 Substituted aryl, the R 2 Selected from hydrogen, halogen, alkyl, alkoxy, ester, One or more of, or R 2 Cyclize with any two adjacent sites of the aromatic group in Ar to form a benzene ring; the aromatic group is phenyl, pyridyl or benzothiophenyl; R 3 is selected from one of hydrogen, silyl, substituted or unsubstituted alkyl, and substituted or unsubstituted phenyl; the substituent in the substituted alkyl is selected from one or more of the following groups: hydrogen, benzyloxy, benzoyloxy, phenoxycarbonyl, The substituent in the substituted phenyl group is an alkoxy group.

2. The azabiaryl compound according to claim 1, characterized in that The azabiaryl compound is one of the compounds shown in the following structure:

3. A method for preparing the azabiaryl compound according to claim 1 or 2, characterized in that: The following steps are involved: The compound represented by formula I, the compound represented by formula II and the compound represented by formula III are reacted in the presence of norbornene, a palladium catalyst, an organic ligand, an alkaline reagent and a solvent to obtain the azabiaryl compound; The structures of the compounds shown in the above formula I to formula III are as follows: Wherein, M is H or KF3B- or a borate group.

4. The preparation method according to claim 3, characterized in that: The compound represented by formula I is selected from one of the compounds represented by the following structures: The compound represented by formula II is selected from one of the compounds represented by the following structures: The compound represented by formula III is selected from one of the compounds represented by the following structures:

5. The preparation method according to claim 3, characterized in that: The palladium catalyst is selected from one or more of palladium acetate, palladium chloride, palladium iodide, palladium trifluoroacetate, tetrakis(triphenylphosphine)palladium, bis(triphenylphosphine)palladium chloride, palladium(II)chlorobis(acetonitrile), tris(dibenzylideneacetone)dipalladium(0), bis(dibenzylideneacetone)palladium, and bis(acetylacetone)palladium(II); The organic ligand is selected from one or more of triphenylphosphine, tri(2-furyl)phosphine, diphenylmethylphosphine, bis(2-diphenylphosphinophenyl)ether, 2-dicyclohexylphosphino-2'-methylbiphenyl, 1,1'-bis(diphenylphosphino)ferrocene, 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl, 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, and bis(diphenylphosphino)methane; The alkaline reagent is selected from one or more of potassium carbonate, cesium carbonate, lithium carbonate, potassium phosphate, potassium hydroxide, and potassium bicarbonate; The solvent is selected from one or more of ethylene glycol dimethyl ether, diethyl ether, methyl tert-butyl ether, acetonitrile, 1,4-dioxane, tetrahydrofuran, N,N-dimethylformamide, N,N-dimethylacetamide, toluene, chlorobenzene, and fluorobenzene.

6. The preparation method according to claim 3, characterized in that: The molar ratio of the compound represented by formula I to the compound represented by formula II and the compound represented by formula III is 1:(1-1.5):(1-2); The molar ratio of the compound represented by formula I to the palladium catalyst, norbornene, organic ligand, and alkaline reagent is 1:0.1:(1-2):(0.1-0.2):(2.5-4.5); The reaction temperature of the reaction is 90-120° C., and the reaction time is 24-48 hours.

7. Use of the azabiaryl compound according to claim 1 or 2 in the preparation of an azahelicene compound, characterized in that: The azabiaryl compound is subjected to a ring-closing reaction in the presence of a catalyst and a solvent to obtain the azahelicene compound; the catalyst is platinum tetrachloride or trifluoromethanesulfonic acid; The azahelicene compounds have the following general structural formulas IV-1 to IV-4: Where Z is C or N, R 3 One selected from hydrogen, silyloxy, and substituted or unsubstituted phenyl.

8. The use according to claim 7, characterized in that: When the R 3 When it is hydrogen, platinum tetrachloride is used as a catalyst for the ring-closing reaction; When the R 3 When the group is silyl, the azabiaryl compound is first subjected to a deprotection treatment, and then a ring-closing reaction is carried out using platinum tetrachloride as a catalyst; When the R 3 When the phenyl group is substituted or unsubstituted, trifluoromethanesulfonic acid is used as a catalyst for the ring-closing reaction.

9. The use according to claim 8, characterized in that: When the R 3 When it is hydrogen or silyl, the molar ratio of the nitrogen heterobiaryl compound to platinum tetrachloride is 1:(0.1-0.2), the reaction temperature of the ring-closure reaction is 120-130°C, and the reaction time is 16-24h; When the R 3 When the phenyl group is substituted or unsubstituted, the molar ratio of the nitrogen biaryl compound to trifluoromethanesulfonic acid is 1:(2-4), the reaction temperature of the ring-closure reaction is 20-30°C, and the reaction time is 3-5h.

10. The use according to claim 7, characterized in that: The azahelicene compound is one of the compounds shown in the following structure:

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