A method for preparing quinoline derivatives

Abstract

This invention relates to the field of organic synthesis and discloses a method for preparing quinoline derivatives. The method involves reacting an enaminoketone compound with an N-phenylglycine ester compound in a solvent under heating in the presence of an oxidant to generate the quinoline derivative. This invention overcomes the dependence on metal catalysts or complex multi-step transformations found in traditional methods, avoids the additional activation steps for intermediates in traditional methods, significantly reduces costs, eliminates the risk of metal residue, meets the requirements of green chemistry, and solves the problem of limited functional group tolerance.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis, and more specifically to a method for preparing quinoline derivatives. Background Technology

[0002] Quinolines and their derivatives, as important nitrogen-containing heterocyclic compounds, have irreplaceable application value in the design of active drug molecules, the development of functional materials, and the total synthesis of natural products. In recent years, quinoline compounds with multiple carbonyl substitutions have become a key research focus in the development of drug lead compounds due to their unique electronic properties and structural modifiability. Among existing technologies, the synthesis of 2,3-dicarbonylquinoline has made significant progress. Typical methods include: a three-component reaction under an iodine / DMSO catalytic system: utilizing the cyclization reaction of acetophenone, aromatic amines, and enamine ketones under neutral redox conditions, 2,3-benzoylquinoline is constructed via an acylimide-iodine complex intermediate. Although this method has good atom economy, it is limited by specific catalytic systems, has a narrow substrate applicability range, and is difficult to achieve asymmetric dicarbonyl substitution. A photocatalytic activation strategy: activating precursors such as ethyl bromodifluoroacetate through a visible light-induced redox process, leading to a multi-component tandem reaction with enamine ketones to generate 2,3-diesterylquinoline. Although this technology expands the reaction types, it requires noble metal photocatalysts and has the problem of controlling side reactions. It is worth noting that the existing methods all focus on the 2,3-position dicarbonyl substitution mode, while the research on the synthesis of 2,4-dicarbonylquinoline with different substitution modes is still blank. Especially in the field of cross-dehydrogenation coupling (CDC) reaction, the traditional method based on the single electron transfer (SET) mechanism to activate N-phenylglycine ester generally has the following technical bottlenecks: (1) Oxidation control problem: conventional strong oxidation system is prone to over-oxidation of α-amino radicals, generating imine ion intermediates. These intermediates have an electron repulsion effect with electron-deficient enamine ketones, which seriously inhibits effective coupling; (2) Reaction path limitation: the existing mechanism relies on the electrophilic properties of imine ions, but this property produces thermodynamically unfavorable electron mismatch with the electron-deficient properties of enamine ketones, resulting in low reaction efficiency; (3) Intermediate stability defects: the carbon radical intermediates generated by the traditional method have too short a lifetime, making it difficult to achieve an effective radical-radical coupling process. Based on the aforementioned technological status, the core issues that urgently need to be addressed in this field include: how to develop novel oxidation regulation systems to achieve the desired oxidation rate of N-phenylglycine ester C(sp) while avoiding excessive oxidation by α-amino free radicals. 3 )-H bond with enamine ketone C(sp 2 The study focuses on the synergistic activation of H bonds; how to establish an effective radical stabilization mechanism to extend the lifetime of key carbon center radicals and promote their effective collision and coupling with electron-deficient enamine ketone radical species; and how to design a concise and efficient synthetic route to avoid multi-step intermediate transformation processes and achieve one-step construction of 2,4-dicarbonylquinoline. Summary of the Invention

[0003] To address the aforementioned technical problems in the prior art, the present invention provides a method for preparing quinoline derivatives, comprising the following steps: reacting an enaminoketone compound with an N-phenylglycine ester compound in a solvent under heating in the presence of an oxidant to generate a quinoline derivative; wherein,

[0004] The structures of enamine ketone compounds are shown in Formula I:

[0005]

[0006] Where: R 1 Selected from aryl, substituted aryl, heteroaryl, cyclopropyl or halogen;

[0007] The structures of N-phenylglycine ester compounds are shown in Formula II:

[0008]

[0009] Among them, R 2 It is selected from alkyl, aryl, substituted aryl or heteroaryl.

[0010] The oxidant is selected from one or more of the following: tert-butyl hydroperoxide, 2,3-dichloro-5,6-dicyanobenzoquinone, benzoyl peroxide, potassium permanganate, di-tert-butyl peroxide, diacetoxyiodobenzene, o-iodobenzoic acid, Dys-Martin oxidant, N-bromosuccinimide, and potassium persulfate.

[0011] The reaction temperature of the method is 50-100 degrees Celsius.

[0012] The molar ratio of the reaction is enamine ketone compound: N-phenylglycine ester compound: oxidant = 1:1:(1.5-3), and the reaction time is 1-3 hours.

[0013] The molar ratio of the reaction was enamine ketone compound: N-phenylglycine ester compound: oxidant = 1:1:2, and the reaction time was 1.5 hours.

[0014] The solvent is acetone, 1,4-dioxane, ethanol, or 1,2-dichloroethane.

[0015] This invention provides a quinoline derivative prepared by the method described above, the structure of which is shown in formula (III):

[0016]

[0017] In equation (III), R 1 Selected from aryl, substituted aryl, heteroaryl, cyclopropyl, or halogen; R 2 It is selected from alkyl, aryl, substituted aryl or heteroaryl.

[0018] The quinoline derivative is a 2,3-dicarbonylquinoline derivative.

[0019] The quinoline derivative has any one of the following structures:

[0020]

[0021] The present invention provides a pharmaceutical intermediate or functional material comprising the aforementioned quinoline derivative.

[0022] The present invention has the following advantages over the prior art:

[0023] This invention provides a method for generating quinoline derivatives by heating enamine ketone compounds with N-phenylglycine ester compounds in a solvent in the presence of an oxidant. This method eliminates the reliance on metal catalysts or complex multi-step conversions found in traditional methods, achieving C(sp) derivatives in a single step. 2 )-H / C(sp 3 The direct cross-dehydrogenation coupling of H-H avoids the additional activation steps of intermediates in traditional methods, significantly reduces costs and eliminates the risk of metal residues, which meets the requirements of green chemistry. The reaction conditions of this application are mild (90°C, 1.5 hours), the solvent system is simple, the operation is convenient and in line with the concept of green chemistry.

[0024] On the other hand, the method described in this invention effectively inhibits the excessive oxidation of α-amino radicals in N-phenylglycine esters, stabilizes the key carbon-center radicals, and promotes their coupling reaction with electron-deficient enamine ketones. Compared with traditional iodine / DMSO or photocatalytic systems, this system precisely regulates the radical process through a single-electron transfer mechanism, solves the problem of electron incompatibility, and significantly improves the reactivity.

[0025] Furthermore, the method described in this invention successfully synthesized structurally diverse 2,3-dicarbonylquinoline derivatives with strong substrate compatibility, tolerating electron-withdrawing groups, electron-donating groups, heterocyclic substituents, and sterically hindered substituents. Moreover, this invention is the first to achieve direct radical coupling between electron-deficient enamine ketones and N-phenylglycine esters, filling a gap in the synthesis of 2,3-dicarbonylquinoline. Attached Figure Description

[0026] Figure 1 This is the X-ray crystal structure of compound 3a in this invention;

[0027] Figure 2 This is a refinement of the crystal data and structure of compound 3a in this invention;

[0028] Figure 3 It is compound 3a in this invention. 1H-NMR (400MHz, CDCl3) spectrum;

[0029] Figure 4 It is compound 3a in this invention. 13 C-NMR (100MHz, CDCl3) spectrum;

[0030] Figure 5 This is the 1H-NMR (400MHz, CDCl3) spectrum of compound 3b in this invention;

[0031] Figure 6 It is compound 3b in this invention. 13 C-NMR (100MHz, CDCl3) spectrum;

[0032] Figure 7 It is compound 3c in this invention. 1 H-NMR (400MHz, CDCl3) spectrum;

[0033] Figure 8 It is compound 3c in this invention. 13 C-NMR (100MHz, CDCl3) spectrum. Detailed Implementation

[0034] To make the objectives, technical solutions, and advantages of this invention clearer, the invention is described below with reference to specific embodiments shown in the accompanying drawings. However, it should be understood that these descriptions are merely exemplary and not intended to limit the scope of the invention. Furthermore, descriptions of well-known structures and technologies are omitted in the following description to avoid unnecessarily obscuring the concept of the invention.

[0035] Example 1

[0036] Enamino ketone 1a (0.2 mmol, accurately weighed) and N-phenylglycine ethyl ester 2a (0.2 mmol, accurately weighed) were added to a dry reaction flask, followed by acetonitrile (2.0 mL, dehydrated using molecular sieves). Potassium persulfate (3.0 equivalents, 0.6 mmol) was added in portions under stirring. The reaction system was sealed, heated to 90 °C, and stirred continuously for 1.5 hours. After the reaction was complete, the mixture was cooled to room temperature and concentrated under reduced pressure to remove the solvent. The crude product was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate, gradient ratio 10:1 to 5:1) to give the target product 3a as a white solid, with a separation yield of 82% (based on 1a).

[0037] Example 2

[0038] The reaction time was adjusted to 0.5 hours and 2.5 hours respectively, according to the conditions described in Example 1. The results showed that at 0.5 hours, the yield of product 3a was 52% (Comparative Example 4-1), indicating that the reaction was not complete.

[0039] 2.5 hours: The yield of product 3a was 78% (Comparative Example 4-2), which is close to the yield of 1.5 hours (82%), proving that 1.5 hours is the optimal duration.

[0040] Example 3

[0041] Adjust the amount of potassium persulfate according to the conditions described in Example 1:

[0042] 1.0 equivalent: The yield of product 3a was 35% (Comparative Example 5-1), indicating that the reaction was incomplete due to insufficient oxidant.

[0043] 4.0 equivalent: The yield of product 3a was 84% ​​(Comparative Example 5-2), which was not significantly different from the effect of 3.0 equivalent. Therefore, 3.0 equivalent was determined to be the economical and efficient choice.

[0044] Example 4

[0045] The molar ratio of enamine ketone 1a to 2a was adjusted according to the conditions described in Example 1:

[0046] 1:1.5 (1a:2a): The yield of product 3a decreased to 68% (Comparative Example 6-1), and the excess of 2a did not improve efficiency.

[0047] 1:0.8 (1a:2a): The yield of product 3a further decreased to 47% (Comparative Example 6-2), proving that 1:1 is the optimal ratio.

[0048] Example 5

[0049] Under the conditions described in Example 1, replace acetonitrile with other solvents:

[0050] Tetrahydrofuran (THF): Product 3a yield 28% (Comparative Example 7-1).

[0051] N,N-Dimethylformamide (DMF): Product 3a yield 19% (Comparative Example 7-2).

[0052] Toluene: Product 3a yield 12% (Comparative Example 7-3).

[0053] Acetonitrile is irreplaceable for the high efficiency of the reaction.

[0054] Oxidizing agent specificity: Compared with other oxidizing agents (such as TBHP, DDQ, IBX, etc.), potassium persulfate significantly improves the yield (Table 1). Temperature dependence: The yield decreases sharply below 90°C (Table 1), indicating that temperature is crucial for free radical generation. Solvent effect: Acetonitrile stabilizes the transition state better than other solvents (Table 1).

[0055]

[0056] Preparation of substrate enamino ketone 1: Synthetic steps of aryl enamino ketones:

[0057]

[0058] The synthesized aryl enamino ketones are shown in the table below:

[0059]

[0060]

[0061] In a round-bottom flask equipped with a magnetic stirrer, ketone S1 (10.0 mmol, 1.0 equivalence) and 1,1-dimethoxy-N,N-dimethylmethylamine S2 (20.0 mmol, 2 equivalence) were added, using toluene (20 mL) as solvent. The mixture was stirred overnight in an oil bath at 110 °C. After the reaction was complete, the reaction mixture was extracted with ethyl acetate and dried over anhydrous sodium sulfate. Subsequently, the reaction mixture was concentrated under reduced pressure, and the residue was purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate (1:1 v / v) to give the corresponding aryl enaminoketones 1a-1q.

[0062] Synthetic steps of arylalkylenamine ketones:

[0063]

[0064] The synthesized aralkylenamine ketones are shown in the table below:

[0065]

[0066] In a round-bottom flask equipped with a magnetic stirrer, ketone S3 (5.0 mmol, 1.0 equivalence) and 1,1-dimethoxy-N,N-dimethylmethylamine S2 (50.0 mmol, 10.0 equivalence) were added. The mixture was stirred overnight in an oil bath at 110 °C. After the reaction was complete, the solvent was removed under vacuum, and the residue was purified by column chromatography using a mixture of petroleum ether and ethyl acetate (1:1 v / v) to give the corresponding alkylenamine ketones 1f and 1r.

[0067] Preparation of glycine derivatives:

[0068] Preparation of N-glycine ethyl ester:

[0069]

[0070] In a 100 mL round-bottom flask, a suitable amount of aniline S5 (10 mmol, 1.0 equivalence) was dissolved in anhydrous ethanol (50 mL). Then, ethyl bromoacetate S4 (10 mmol, 1.0 equivalence) was added dropwise. The mixture was heated to 70 °C and refluxed for 10 hours. The reaction progress was monitored by thin-layer chromatography. After the reaction was complete, the mixture was extracted with ethyl acetate and the precipitate was filtered. The filtrate was concentrated under vacuum to give products 2a-2i.

[0071] The synthesized glycine derivatives are shown in the table below:

[0072]

[0073] Preparation of α-aminoacetophenone

[0074]

[0075] A mixture of aniline S7 (1 mmol, 1.0 equivalence) and 2-bromoacetophenone compound S6 (1.2 mmol, 1.2 equivalence) was dissolved in 10 mL of methanol. Sodium bicarbonate (1.5 mmol) was then added to the solution, and the mixture was stirred at room temperature. After the reaction was complete (monitored by thin-layer chromatography (TLC), the mixture was extracted with ethyl acetate (15 mL × 2). The organic layer was washed with water (15 mL × 2) and dried over anhydrous sodium sulfate. The organic layer was concentrated using a rotary evaporator, and the crude product was purified by silica gel (200-300 mesh) column chromatography. A yellow solid, 1-phenyl-2-(phenylamino)acetophenone, was obtained.

[0076]

[0077] Preparation methods of compounds 3a-3r and 4a-4l

[0078]

[0079] Enamino ketone derivative 1 (0.2 mmol, 1.0 equivalence), glycine derivative 2 (0.2 mmol, 1.0 equivalence), and potassium persulfate (0.6 mmol, 3.0 equivalence) were added to a 10.0 mL reaction tube containing 2.0 mL (0.1 M) acetonitrile (MeCN). The mixture was stirred in an oil bath maintained at 90 °C for 1.5 h, and the reaction progress was monitored by thin-layer chromatography. Subsequently, the reaction system was cooled to room temperature, the reaction was quenched with 10 mL of saturated sodium chloride solution, and then extracted three times with 20.0 mL of ethyl acetate. The organic layers were combined, dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated under reduced pressure. The residues were purified by silica gel rapid column chromatography to give products 3a-3r and 4a-4l. The products were further identified by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0080] Example 6 (The synthesis conditions for 3b-3o are the same as those for 3a)

[0081] Compound 3b (para-chlorosubstituted): Replacing 1a with para-chlorosubstituted enamine ketone 1b yielded 58% product 3b.

[0082] Compound 3c (p-iodine substitution): Replacing 1a with p-iodine-substituted enamine ketone 1c yielded a 53% product 3c.

[0083] Compound 3d (electron-donating group): Using enamine ketone 1d containing an electron-donating group as a substrate, the yield of product 3d was 71%.

[0084] Compound 3e (electron-donating group): Using enamine ketone 1e, which is substituted with other electron-donating groups, as a substrate, the yield of product 3e is 72%.

[0085] Compound 3i (electron-withdrawing group): Using enamine ketone 1i containing an electron-withdrawing group as a substrate, the yield of product 3i was 46%.

[0086] Compound 3j (electron-withdrawing group): Using enamine ketone 1j, which is substituted with other electron-withdrawing groups, as a substrate, the yield of product 3j was 45% (Table 2).

[0087] Compound 3f (cyclopropane-substituted): Using cyclopropane-substituted enamine ketone 1f as a substrate, the yield of product 3f was 57%, indicating that the reaction is tolerant to ring-strained structures.

[0088] Compound 3o (heterocyclic substitution): Using enamine ketone 1o containing a thiophene ring as a substrate, the yield of product 3o was 53%.

[0089] Example 7 (The synthesis method of 4a-4i is the same as that of 3a)

[0090] Compound 4a (monosubstituted phenyl): Using N-phenylglycine ethyl ester 2a as a substrate, the yield of product 4a was 71%.

[0091] Compound 4b (disubstituted phenyl): Using glycine ester 2b containing disubstituted phenyl as a substrate, the yield of product 4b was 74%.

[0092] Compound 4d (para-chlorosubstituted): Using para-chlorosubstituted N-phenylglycine ester 2d as a substrate, the yield of product 4d was 58%.

[0093] Compound 4f (m-methyl substituted): Using m-methyl substituted glycine ester 2f as a substrate, the yield of product 4f was 73%.

[0094] Compound 4c (β-naphthyl): Using β-naphthyl-substituted glycine ester 2c as a substrate, the yield of product 4c was 60%.

[0095] Compound 4h (methyl ester): The yield of product 4h was 75% when N-phenylglycine methyl ester 2h was substituted for ethyl ester.

[0096] Compound 4i (tert-butyl ester): Using N-phenylglycine tert-butyl ester 2i as a substrate, the yield of product 4i was 41%.

[0097] The above yields are calculated based on the molar amount of the enaminoketone substrate (1a or its derivative).

[0098] This application is compatible with electron-withdrawing groups (Cl, I), electron-donating groups (OCH3, CH3), and heterocyclic substituents on the aromatic ring of enamine ketones; it can efficiently convert benzene ring substituents (monosubstituted, disubstituted, halogenated, alkyl) and naphthyl derivatives of -N-arylglycine esters; it is adaptable to ester types (ethyl ester, methyl ester, tert-butyl ester), but the yield of tert-butyl ester is low (41%).

[0099] Through systematic verification in Examples 6-7, the reaction system of this invention exhibits a broad substrate applicability, enabling the efficient synthesis of 2,3-dicarbonylquinoline derivatives containing various substituents (yields of 36%-84%). This method demonstrates good tolerance to structurally complex substrates (such as cyclopropane and heterocycles) and various ester derivatives, possessing significant potential for industrial applications.

[0100]

[0101] This application further broadens the substrate scope of this reaction. The method was successfully applied to enamine ketones containing ester groups, yielding 2,3-diesterylquinoline (3r) in 54% yield. Furthermore, this conversion reaction can synthesize 2,3-diketoquinoline aryl compounds (4j-4l) with different substituents (m-methyl, m-chloro, m-isopropyl) in moderate to good yields (41%-63%). These experimental results demonstrate the excellent substrate versatility of this reaction system. Under the conditions of this invention, enamine ketone 1a (10.0 mmol) reacted with N-phenylglycine ester 2a to give 3a (1.5 g) in 76% isolated yield. Subsequently, we explored its synthetic applications using 3a as a representative substrate. In ethanol, 3a reacted with hydrazine hydrate to give pyridopyridazine derivative 5, confirming its potential in constructing complex heterocyclic skeletons. Furthermore, under acidic conditions, 3a underwent transesterification with methanol to generate methyl ester derivative 6. These transformation reactions not only highlight the synthetic versatility of 3a but also establish its value as a general synthetic building block. Successful cyclization and transesterification reactions together reveal the enormous potential of 3a in constructing diverse molecular structures, confirming its practical application value in chemical transformations. The reaction conditions for route b were: 3a (0.5 mmol), N₂H₄·H₂O (2 equivalents), ethanol (2 mL), reflux for 12 hours. The reaction conditions for route c were: 3a (0.5 mmol), methanol (2 mL), HCl (1 equivalent), reaction at 70 °C for 12 hours.

[0102]

[0103] This invention proposes a highly efficient potassium persulfate-mediated cross-dehydrogenation coupling strategy specifically designed for constructing 2,3-diketoquinoline skeletons of significant synthetic value. This application eliminates the dependence on metal catalysts or complex multi-step transformations inherent in traditional methods, achieving C(sp) in a single step. 2 )-H / C(sp 3 The direct cross-dehydrogenation coupling of H-H avoids the additional activation steps of intermediates in traditional methods, significantly reduces costs and eliminates the risk of metal residues, which meets the requirements of green chemistry. The reaction conditions of this application are mild, the solvent system is simple, the operation is convenient and conforms to the concept of green chemistry.

[0104] On the other hand, the method described in this invention can effectively suppress the excessive oxidation of α-amino radicals in N-phenylglycine esters, stabilize the key carbon-center radicals, and promote their coupling reaction with electron-deficient enamine ketones. Compared with traditional iodine / DMSO or photocatalytic systems, this invention precisely controls the radical process through a single-electron transfer mechanism, solves the problem of electron incompatibility, and significantly improves the reactivity.

[0105] The method described in this invention successfully synthesized structurally diverse 2,3-dicarbonylquinoline derivatives with strong substrate compatibility, tolerating electron-withdrawing groups, electron-donating groups, heterocyclic substituents, and sterically hindered substituents. Furthermore, this invention achieves, for the first time, the direct radical coupling of electron-deficient enamine ketones with N-phenylglycine esters, filling a gap in the synthesis of 2,3-dicarbonylquinolines. This invention utilizes its high oxidation potential to simultaneously activate both enamine ketones and N-glycine esters in the reaction system. Through kinetic control, it can regulate the radical / radical coupling process between the N-glycine derivative and the electron-deficient enamine ketone, thereby ensuring smooth reaction progress and generating the target product in high yield.

[0106] The data for the compounds involved in this invention are as follows:

[0107]

[0108] Ethyl3-benzoylquinoline-2-carboxylate

[0109] 49.3 mg, 82% yield. Yellow solid, (Flash column chromatography eluent, petroleum ether / ethylacetate=20 / 1, V / V).

[0110] 1 H NMR (400 MHz, Chloroform-d) δ8.35 (d, J = 8.8 Hz, 1H), 8.33 (s, 1H), 7.94-7.86 (m, 2H), 7.82 (d, J = 7.2 Hz, 2H), 7.72 (t, J = 7.0 Hz, 1H), 7.61 (t, J = 7.4 Hz,1H),7.48(t,J=7.6 Hz,2H),4.27(q,J=7.2 Hz,2H),1.20(t,J=7.2 Hz,3H).

[0111] 13 C NMR (100 MHz, CDCl3) δ193.7,164.2,146.8,146.4,136.3,136.0,132.5,132.1,130.6,129.5,128.6,128.3,127.7,127.1,126.5,61.6,12.8.

[0112] HRMS(ESI)m / z:Calcd for C 19 H 16 NO3 + [M+H]+ :306.1125;found:306.1124.

[0113]

[0114] Ethyl 3-(4-chlorobenzoyl)quinoline-2-carboxylate

[0115] 40.4 mg,58%yield.White solid,(Flash column chromatography eluent,petroleumether / ethyl acetate=20 / 1,V / V).

[0116] 1 H NMR(400 MHz,Chloroform-d)δ8.36(d,J=8.6 Hz,1H),8.31(s,1H),7.93(d,J=8.8Hz,1H),7.91-7.88(m,1H),7.82(t,J=1.7 Hz,1H),7.74(t,J=7.0 Hz,1H),7.67-7.65(m,1H),7.58-7.55(m,1H),7.41(t,J=7.8 Hz,1H),4.32(q,J=7.2 Hz,2H),1.25(t,J=7.2 Hz,3H).

[0117] 13 C NMR(100 MHz,CDCl3)δ192.4,164.1,146.5,146.4,137.7,136.2,134.1,132.4,131.6,130.8,129.5,129.0,128.5,128.4,127.1,126.7,61.7,12.9.

[0118] HRMS(ESI)m / z:Calcd for C 19 H 15 ClNO3 + [M+H] + :340.0735;found:340.0733.

[0119]

[0120] Ethyl 3-(4-iodobenzoyl)quinoline-2-carboxylate

[0121] 32.5 mg,51%yield.White solid,(Flash column chromatography eluent,petroleumether / ethyl acetate=15 / 1,V / V).

[0122] 1 H NMR(400 MHz,Chloroform-d)δ8.35(d,J=8.5 Hz,1H),8.30(s,1H),7.94-7.87(m,2H),7.84(d,J=8.5 Hz,2H),7.73(t,J=7.8 Hz,1H),7.53(d,J=8.5 Hz,2H),4.31(q,J=7.2 Hz,2H),1.26(t,J=7.2 Hz,3H).

[0123] 13 C NMR(100 MHz,CDCl3)δ193.0,164.1,146.5,146.4,137.0,136.1,135.4,131.7,130.8,129.8,129.5,128.5,127.1,126.5,61.7,12.9.

[0124] HRMS(ESI)m / z:Calcd for C 19 H 15 INO3 + [M+H] + :432.0091;found:432.0090.

[0125]

[0126] Ethyl 3-(4-methylbenzoyl)quinoline-2-carboxylate

[0127] 45.3 mg,65%yield.Yellow solid,(Flash column chromatography eluent,petroleumether / ethyl acetate=20 / 1,V / V).

[0128] 1H NMR(400 MHz,Chloroform-d)δ8.34(d,J=8.0 Hz,1H),8.31(s,1H),7.91(d,J=8Hz,2H),7.89-7.85(m,1H),7.73(d,J=8.0 Hz,3H),7.28(s,1H),4.28(q,J=7.2 Hz,2H),2.43(s,3H),1.21(t,J=7.2 Hz,3H).

[0129] 13 C NMR(100 MHz,CDCl3)δ193.3,164.2,146.4,143.5,136.1,133.5,132.3,130.5,129.5,128.8,128.4,128.2,127.1,126.6,61.5,20.7,12.8.

[0130] HRMS(ESI)m / z:Calcd for C 20 H 18 NO3 + [M+H] + :320.1281;found:320.1280.

[0131]

[0132] Ethyl 3-([1,1'-biphenyl]-4-carbonyl)quinoline-2-carboxylate

[0133] 44.7 mg,72%yield.Yellow solid,(Flash column chromatography eluent,petroleumether / ethyl acetate=20 / 1,V / V).

[0134] 1 H NMR(400 MHz,Chloroform-d)δ8.37-8.36(m,2H),7.95-7.87(m,4H),7.76-7.72(m,1H),7.70(d,J=8.0 Hz,2H),7.65-7.62(m,2H),δ7.48(t,J=8.0 Hz,2H),7.41(t,J=8.0 Hz,1H).,4.32(q,J=7.2 Hz,2H),1.24(t,J=7.2 Hz,3H).

[0135] 13C NMR(100 MHz,CDCl3)δ193.3,164.3,146.8,146.4,145.2,138.7,136.2,134.7,132.3,130.6,129.5,129.2,128.3,128.0,127.4,127.1,126.33,126.29,61.6,12.8.HRMS(ESI)m / z:Calcd for C 25 H 20 NO3 + [M+H] + :382.1438;found:382.1436.

[0136]

[0137] Ethyl 3-(cyclopropanecarbonyl)quinoline-2-carboxylate

[0138] 42.6 mg,57%yield.Yellow oil,(Flash column chromatography eluent,petroleum ether / ethylacetate=15 / 1,V / V).

[0139] 1 H NMR(400 MHz,Chloroform-d)δ8.57(s,1H),8.25(d,J=8.4 Hz,1H),7.95(d,J=8.2Hz,1H),7.88-7.84(m,1H),7.69(t,J=7.5 Hz,1H),4.51(q,J=7.2 Hz,2H),2.57-2.51(m,1H),1.43(t,J=7.2 Hz,3H),1.38-1.34(m,2H),1.18-1.37(m,2H).

[0140] 13 C NMR(100 MHz,CDCl3)δ200.3,165.6,148.1,146.6,135.8,131.5,130.9,129.1,127.8,127.4,126.2,61.5,19.1,13.1,11.7.

[0141] HRMS(ESI)m / z:Calcd for C 16 H 16 NO3 + [M+H] +:270.1125;found:270.1124.

[0142]

[0143] Ethyl 3-(3-bromobenzoyl)quinoline-2-carboxylate

[0144] 25.6 mg,36%yield.Yellow solid,(Flash column chromatography eluent,petroleumether / ethyl acetate=20 / 1,V / V).

[0145] 1 H NMR(400 MHz,Chloroform-d)δ8.36(d,J=8.6 Hz,1H),8.31(s,1H),7.97(t,J=1.8Hz,1H),7.94(d,J=7.2 Hz,1H),7.91-7.88(m,1H),7.76-7.69(m,3H),7.35(t,J=7.8 Hz,1H),4.33(q,J=7.2 Hz,2H),1.26(t,J=7.2 Hz,3H).

[0146] 13 C NMR(100 MHz,CDCl3)δ193.3,165.1,147.5,147.4,138.9,137.2,136.3,132.6,132.3,131.8,130.6,130.3,129.5,128.2,127.6,123.1,62.8,13.9.

[0147] HRMS(ESI)m / z:Calcd for C 19 H 15 BrNO3 + [M+H] + :384.0230;found:384.0229.

[0148]

[0149] Ethyl 3-(2-naphthoyl)quinoline-2-carboxylate

[0150] 45.9 mg,71%yield.Yellow solid,(Flash column chromatography eluent,petroleumether / ethyl acetate=20 / 1,V / V).

[0151] 1 H NMR(400 MHz,Chloroform-d)δ8.40(s,1H),8.39(d,J=9.0 Hz,1H),8.13(s,1H),8.08-8.06(m,1H),7.97-7.89(m,4H),7.83(d,J=8.1 Hz,1H),7.74(t,J=7.2 Hz,1H),7.62(t,J=8.0 Hz,1H),7.53(t,J=7.2 Hz,1H),4.23(q,J=7.2 Hz,2H),1.14(t,J=7.2 Hz,3H).

[0152] 13 C NMR(100 MHz,CDCl3)δ193.7,164.2,146.9,146.5,136.4,134.7,133.5,132.3,131.3,131.0,130.6,129.5,128.6,128.3,127.84,127.81,127.1,126.8,126.6,126.0,123.5,61.6,12.8.

[0153] HRMS(ESI)m / z:Calcd for C 23 H 18 NO3 + [M+H] + :356.1281;found:356.1280.

[0154]

[0155] Ethyl 3-(4-nitrobenzoyl)quinoline-2-carboxylate

[0156] 27.3 mg,46%yield.Yellow solid,(Flash column chromatography eluent,petroleumether / ethyl acetate=20 / 1,V / V).

[0157] 1H NMR(400 MHz,Chloroform-d)δ8.63-8.62(m,1H),8.47-8.44(m,1H),8.39(d,J=9.0Hz,1H),8.32(s,1H),8.16-8.14(m,1H),7.94(t,J=7.2 Hz,2H),7.77(t,J=6.6 Hz,1H),7.69(t,J=5.8 Hz,1H),4.35(q,J=7.2 Hz,2H),1.28(t,J=7.2 Hz,3H).

[0158] 13 C NMR(100 MHz,CDCl3)δ191.5,164.1,147.4,146.6,145.9,137.7,136.0,133.8,131.3,131.0,129.7,129.0,128.8,127.1,126.6,126.5,123.1,61.9,13.0.

[0159] HRMS(ESI)m / z:Calcd for C 19 H 15 N2O5 + [M+H] + :351.0975;found:351.0974.

[0160]

[0161] Ethyl 3-(4-(methylsulfonyl)benzoyl)quinoline-2-carboxylate

[0162] 23.6 mg,45%yield.Yellow solid,(Flash column chromatography eluent,petroleumether / ethyl acetate=15 / 1,V / V).

[0163] 1 H NMR(400 MHz,Chloroform-d)δ8.23(d,J=9.1 Hz,1H),8.20(s,1H),8.10(d,J=2.0Hz,1H),8.07-8.04(m,3H),7.99-7.97(m,3H),4.33(q,J=7.2 Hz,2H),3.09(s,3H),1.27(t,J=7.2 Hz,3H).

[0164] 13 C NMR(100 MHz,CDCl3)δ192.9,164.9,147.2,146.1,144.5,140.9,135.9,135.7,133.4,132.1,130.2,130.1,129.2,128.6,127.9,124.3,118.3,63.7,44.3,14.0.

[0165] HRMS(ESI)m / z:Calcd for C 20 H 18 NO5S + [M+H] + :384.0900;found:384.0899.

[0166]

[0167] Ethyl 3-(4-(tert-butoxycarbonyl)benzoyl)quinoline-2-carboxylate

[0168] 49.3 mg,63%yield.Yellow solid,(Flash column chromatography eluent,petroleumether / ethyl acetate=20 / 1,V / V).

[0169] 1 H NMR(400 MHz,Chloroform-d)δ8.36(d,J=8.6 Hz,1H),8.32(s,1H),8.07(d,J=8.5Hz,2H),7.94-7.91(m,1H),7.91-7.88(m,1H),7.85(d,J=8.5 Hz,2H),7.74(t,J=7.2 Hz,1H),4.27(q,J=7.2 Hz,2H),1.60(s,9H),1.23(t,J=7.2 Hz,3H).

[0170] 13 C NMR(100 MHz,CDCl3)δ193.1,164.1,163.7,146.5,138.9,136.3,135.0,131.8,130.8,129.5,128.7,128.5,128.3,127.1,126.5,80.9,61.7,27.1,12.8.

[0171] HRMS(ESI)m / z:Calcd for C 24 H 24 NO5[M+H] + :406.1649;found:406.1648.

[0172]

[0173] Ethyl 3-(4-(methoxycarbonyl)benzoyl)quinoline-2-carboxylate

[0174] 32.1 mg,53%yield.Yellow solid,(Flash column chromatography eluent,petroleumether / ethyl acetate=15 / 1,V / V).

[0175] 1 H NMR(400 MHz,Chloroform-d)δ8.37(d,J=8.5 Hz,1H),8.34(s,1H),8.13(d,J=8.2Hz,2H),7.93(t,J=7.2 Hz,2H),7.87(d,J=8.2 Hz,2H),7.75(t,J=7.5 Hz,1H),4.29(q,J=7.2 Hz,2H),3.96(s,3H),1.22(t,J=7.2 Hz,3H).

[0176] 13 C NMR(100 MHz,CDCl3)δ193.1,165.1,164.1,146.5,146.4,139.3,136.3,133.1,131.7,130.8,129.5,128.9,128.5,128.4,127.1,126.5,61.7,51.6,12.8.

[0177] HRMS(ESI)m / z:Calcd for C 21 H 18 NO5 + [M+H] + :364.1179;found:364.1179.

[0178]

[0179] Ethyl 3-(4-methoxybenzoyl)quinoline-2-carboxylate

[0180] 36.2 mg,61%yield.Yellow solid,(Flash column chromatography eluent,petroleumether / ethyl acetate=20 / 1,V / V).

[0181] 1 H NMR(400 MHz,Chloroform-d)δ8.34(d,J=8.5 Hz,1H),8.30(s,1H),7.90(d,J=8.6Hz,1H),7.88-7.84(m,1H),7.81(d,J=8.8 Hz,2H),7.71(t,J=7.2 Hz,1H),6.95(d,J=8.8 Hz,2H),4.30(q,J=7.2 Hz,2H),3.88(s,3H),1.23(t,J=7.2 Hz,3H).

[0182] 13 C NMR(100 MHz,CDCl3)δ192.4,164.3,162.9,146.8,146.3,135.9,132.5,131.0,130.4,129.5,129.0,128.2,127.0,126.6,112.9,61.5,54.6,12.8.

[0183] HRMS(ESI)m / z:Calcd for C 20 H 18 NO4[M+H] + :336.1230;found:336.1228.

[0184]

[0185] Ethyl 3-(3,4-dimethoxybenzoyl)quinoline-2-carboxylate

[0186] 35.9 mg,57%yield.Yellow oil,(Flash column chromatography eluent,petroleum ether / ethylacetate=15 / 1,V / V).

[0187] 1H NMR(400 MHz,Chloroform-d)δ8.35(d,J=8.5 Hz,1H),8.32(s,1H),7.92-7.86(m,2H),7.72(t,J=7.2 Hz,1H),7.62(d,J=1.9 Hz,1H),7.19-7.17(m,1H),6.82(d,J=8.4 Hz,1H),4.30(q,J=7.2 Hz,2H),3.96(s,3H),3.94(s,3H),1.24(t,J=7.2 Hz,3H).

[0188] 13 C NMR(100 MHz,CDCl3)δ192.4,164.3,152.7,148.3,146.8,146.3,136.1,132.3,130.5,129.4,129.2,128.3,127.0,126.6,124.5,123.5,109.6,108.9,61.6,55.1,12.9.

[0189] HRMS(ESI)m / z:Calcd for C 21 H 20 NO5 + [M+H] + :366.1336;found:366.1336.

[0190]

[0191] Ethyl 3-(benzo[d][1,3]dioxole-5-carbonyl)quinoline-2-carboxylate

[0192] 36.1 mg,53%yield.Yellow solid,(Flash column chromatography eluent,petroleumether / ethyl acetate=20 / 1,V / V).

[0193] 1H NMR(400 MHz,Chloroform-d)δ8.33(d,J=8.5 Hz,1H),8.28(s,1H),7.90(d,J=8.7Hz,1H),7.88-7.84(m,1H),7.71(t,J=7 Hz,1H),7.44(d,J=1.7 Hz,1H),7.27-7.23(m,1H),6.81(d,J=8.1 Hz,1H),6.07(s,2H),4.33(q,J=7.2 Hz,2H),1.26(t,J=7.2 Hz,3H).

[0194] 13 C NMR(100 MHz,CDCl3)δ192.0,164.2,151.3,147.4,146.6,146.3,135.9,132.4,130.9,130.5,129.5,128.3,127.0,126.5,125.9,107.8,106.9,101.1,61.6,12.9.

[0195] HRMS(ESI)m / z:Calcd for C 20 H 16 NO5 + [M+H] + :350.1023;found:350.1021.

[0196]

[0197] Ethyl 3-(furan-2-carbonyl)quinoline-2-carboxylate

[0198] 34.2 mg,52%yield.Yellow solid,(Flash column chromatography eluent,petroleumether / ethyl acetate=20 / 1,V / V).

[0199] 1H NMR(400 MHz,Chloroform-d)δ8.47(s,1H),8.33(d,J=8.4 Hz,1H),7.95(d,J=8.1Hz,1H),7.91-7.86(m,1H),7.77-7.69(m,1H),7.66-7.64(m,1H),7.19-7.17(m,1H),6.61-6.59(m,1H),4.36(q,J=7.2 Hz,2H),1.28(t,J=7.2 Hz,3H).

[0200] 13 C NMR(100 MHz,CDCl3)δ180.7,164.3,146.3,136.7,130.9,130.8,129.44,129.38,128.3,128.2,127.3,127.2,126.5,118.5,111.7,61.6,12.9。

[0201] HRMS(ESI)m / z:Calcd for C 17 H 14 NO4 + [M+H] + :296.0917;found:296.0915.

[0202]

[0203] Ethyl 3-(thiophene-2-carbonyl)quinoline-2-carboxylate

[0204] 31.3 mg,67%yield.Yellow solid,(Flash column chromatography eluent,petroleumether / ethyl acetate=20 / 1,V / V).

[0205] 1 H NMR(400 MHz,Chloroform-d)δ8.41(s,1H),8.34(d,J=8.4 Hz,1H),7.93(t,J=8.0Hz,1H),7.90(d,J=8.2 Hz,1H),7.77(d,J=4.9 Hz,1H),7.75(t,J=7.8 Hz,1H),7.42(d,J=3.8 Hz,1H),7.13(t,J=4.7 Hz,1H),4.35(q,J=7.2 Hz,2H),1.28(t,J=7.2Hz,3H).

[0206] 13 C NMR(100 MHz,CDCl3)δ185.7,164.2,146.5,143.2,136.0,134.1,133.8,131.7,130.7,129.5,128.3,127.3,127.1,126.4,61.6,12.8.

[0207] HRMS(ESI)m / z:Calcd for C 17 H 14 NO3S + [M+H] + :312.0689;found:312.0687.

[0208]

[0209]

[0210] Diethyl quinoline-2,3-dicarboxylate

[0211] 29.4 mg,54%yield.Yellow oil,(Flash column chromatography eluent,petroleum ether / ethylacetate=15 / 1,V / V).

[0212] 1 H NMR(400 MHz,Chloroform-d)δ8.79(s,1H),8.21(d,J=8.4 Hz,1H),7.95(d,J=8.2Hz,1H),7.86(t,J=7.6 Hz,1H),7.69-7.66(m,1H),4.53(q,J=7.2 Hz,2H),4.44(q,J=7.2 Hz,2H),1.45(t,J=7.2 Hz,3H),1.42(t,J=6.8 Hz,3H).

[0213] 13 C NMR(100 MHz,CDCl3)δ165.9,164.1,150.0,147.0,138.6,131.3,128.8,127.6,127.6,126.0,121.4,61.4,61.0,13.2,13.1.

[0214] HRMS(ESI)m / z:Calcd for C 15 H16 NO4 + [M+H] + :274.1074;found:274.1076.

[0215]

[0216] Ethyl 3-benzoyl-6-methylquinoline-2-carboxylate

[0217] 45.6 mg,65%yield.Yellow solid,(Flash column chromatography eluent,petroleumether / ethyl acetate=20 / 1,V / V).

[0218] 1 H NMR(400 MHz,Chloroform-d)δ8.24-8.22(m,2H),7.81(d,J=7.2 Hz,2H),7.72-7.69(m,1H),7.67(s,1H),7.61-7.57(m,1H),7.46(t,J=7.9 Hz,2H),4.26(q,J=7.2Hz,2H),2.59(s,3H),1.19(t,J=7.2 Hz,3H).

[0219] 13 C NMR(100 MHz,CDCl3)δ193.9,164.2,145.7,145.0,138.8,136.1,135.4,133.0,132.4,132.3,129.1,128.6,127.7,126.7,125.8,61.5,20.8,12.8.

[0220] HRMS(ESI)m / z:Calcd for C 20 H 18 NO3 + [M+H] + :320.1281;found:320.1280.

[0221]

[0222] Ethyl 3-benzoyl-5,7-dimethylquinoline-2-carboxylate

[0223] 47.1 mg,71%yield.Yellow solid,(Flash column chromatography eluent,petroleumether / ethyl acetate=15 / 1,V / V).

[0224] 1 H NMR(400 MHz,Chloroform-d)δ8.42(s,1H),7.96(s,1H),7.82-7.79(m,2H),7.60-7.56(m,1H),7.46(t,J=7.8 Hz,2H),7.37(s,1H),4.22(q,J=7.2 Hz,2H),2.65(s,3H),2.56(s,3H),1.17(t,J=7.2 Hz,3H).

[0225] 13 C NMR(100 MHz,CDCl3)δ194.1,164.3,147.2,146.1,141.0,136.3,133.8,132.7,132.3,131.1,130.9,128.5,127.6,126.5,124.3,61.4,21.0,17.5,12.8.

[0226] HRMS(ESI)m / z:Calcd for C 21 H 20 NO3 + [M+H] + :334.1438;found:334.1439.

[0227]

[0228] Ethyl 3-benzoylbenzo[g]quinoline-2-carboxylate

[0229] 39.4 mg,60%yield.Yellow solid,(Flash column chromatography eluent,petroleumether / ethyl acetate=30 / 1,V / V).

[0230] 1H NMR(400 MHz,Chloroform-d)δ9.08(s,1H),8.63-8.58(m,1H),8.20(d,J=9.2Hz,1H),8.13(d,J=9.2 Hz,1H),8.01-7.98(m,1H),7.86-7.83(m,2H),7.75-7.72(m,2H),7.64-7.58(m,1H),7.48(t,J=7.9 Hz,2H),4.26(q,J=7.2 Hz,2H),1.20(t,J=7.2 Hz,3H).

[0231] 13 C NMR(100 MHz,CDCl3)δ194.1,164.1,147.0,145.6,136.2,132.7,132.5,132.2,131.6,130.8,128.6,128.0,127.9,127.8,127.7,127.0,126.9,125.0,122.4,61.6,12.8.

[0232] HRMS(ESI)m / z:Calcd for C 23 H 18 NO3 + [M+H] + :356.1281;found:356.1283.

[0233]

[0234] Ethyl 3-benzoyl-6-chloroquinoline-2-carboxylate

[0235] 47.3 mg,58%yield.Yellow solid,(Flash column chromatography eluent,petroleumether / ethyl acetate=20 / 1,V / V).

[0236] 1 H NMR(400 MHz,Chloroform-d)δ8.29(d,J=9.0 Hz,1H),8.23(s,1H),7.90(d,J=2.2Hz,1H),7.82-7.79(m,3H),7.63-7.60(m,1H),7.48(t,J=7.8 Hz,2H),4.27(q,J=7.2 Hz,2H),1.20(t,J=7.2 Hz,3H).

[0237] 13 C NMR(100 MHz,CDCl3)δ193.2,163.9,146.9,144.7,135.1,134.4,133.1,132.6,131.6,131.0,128.6,128.3,127.8,127.2,125.7,61.7,13.1.

[0238] HRMS(ESI)m / z:Calcd for C 19 H 15 ClNO3 + [M+H] + :340.0735;found:340.0732.

[0239]

[0240] Ethyl 3-benzoyl-6-iodoquinoline-2-carboxylate

[0241] 34.5 mg,65%yield.Yellow solid,(Flash column chromatography eluent,petroleumether / ethyl acetate=15 / 1,V / V).

[0242] 1 H NMR(400 MHz,Chloroform-d)δ8.31(d,J=1.9 Hz,1H),8.19(s,1H),8.12-8.09(m,1H),8.05(d,J=8.9 Hz,1H),7.80-7.78(m,2H),7.64-7.59(m,1H),7.47(t,J=8.0Hz,2H),4.27(q,J=7.2 Hz,2H),1.20(t,J=7.2 Hz,3H).

[0243] 13 C NMR(100 MHz,CDCl3):δ193.2,163.9,147.1,145.3,139.4,137.2,135.8,135.7,134.8,132.9,132.6,130.8,128.6,128.0,127.8,61.7,12.8.

[0244] HRMS(ESI)m / z:Calcd for C 19 H 15 INO3+ [M+H] + :432.0091;found:432.0090.

[0245]

[0246] Ethyl 3-benzoyl-7-methylquinoline-2-carboxylate

[0247] 48.5 mg,73%yield.Yellow solid,(Flash column chromatography eluent,petroleumether / ethyl acetate=15 / 1,V / V).

[0248] 1 H NMR(400 MHz,Chloroform-d)δ8.28(s,1H),8.12(s,1H),7.84-7.78(m,2H),7.60(t,J=7.4 Hz,1H),7.54(d,J=7.0 Hz,2H),7.47(t,J=7.8 Hz,2H),4.26(q,J=7.2Hz,2H),2.62(s,3H),1.20(t,J=7.2 Hz,3H).

[0249] 13 C NMR(100 MHz,CDCl3)δ193.8,164.4,146.9,146.7,136.1,136.0,132.4,131.3,130.6,128.6,128.7,128.4,127.68,127.65,126.7,61.5,21.1,12.8.

[0250] HRMS(ESI)m / z:Calcd for C 20 H 18 NO3 + [M+H] + :320.1281;found:320.1280.

[0251]

[0252] Ethyl 3-benzoyl-7-chloroquinoline-2-carboxylate

[0253] 32.1 mg,53%yield.Yellow solid,(Flash column chromatography eluent,petroleumether / ethyl acetate=15 / 1,V / V).

[0254] 1 H NMR(400 MHz,Chloroform-d)δ8.36(s,1H),8.32(s,1H),7.86(d,J=8.7 Hz,1H),7.81(d,J=7.2 Hz,2H),7.69-7.66(m,1H),7.62(t,J=7.4 Hz,1H),7.49(t,J=7.8Hz,2H),4.27(q,J=7.2 Hz,2H),1.21(t,J=7.2 Hz,3H).

[0255] 13 C NMR(100 MHz,CDCl3)δ193.3,163.9,148.0,146.7,136.8,136.1,132.6,132.2,129.4,129.2,128.6,128.4,128.2,127.8,127.5,61.7,12.8.

[0256] HRMS(ESI)m / z:Calcd for C 19 H 15 ClNO3 + [M+H] + :340.0735;found:340.0737.

[0257]

[0258] Methyl 3-benzoylquinoline-2-carboxylate

[0259] 39.8 mg,75%yield.Yellow oil,(Flash column chromatography eluent,petroleum ether / ethylacetate=15 / 1,V / V).

[0260] 1H NMR(600 MHz,Chloroform-d)δ8.22(s,1H),8.21(d,J=9.2 Hz,1H),8.09(d,J=2.0Hz,1H),7.96-7.94(m,1H),7.81-7.79(m,2H),7.62(t,J=7.4 Hz,1H),7.48(t,J=7.8 Hz,3H),3.84(s,3H).

[0261] 13 C NMR(150 MHz,CDCl3)δ193.2,164.3,146.6,144.9,135.7,135.0,134.3,133.2,132.7,130.96,129.1,128.6,127.8,127.7,122.9,52.3.

[0262] HRMS(ESI)m / z:Calcd for C 18 H 14 NO3 + [M+H] + :292.0968;found:292.0967.

[0263]

[0264] Tert-butyl 3-benzoylquinoline-2-carboxylate

[0265] 28.3 mg,41%yield.Yellow solid,(Flash column chromatography eluent,petroleumether / ethyl acetate=15 / 1,V / V).

[0266] 1 H NMR(400 MHz,Chloroform-d)δ8.36(d,J=8.6 Hz,1H),8.30(s,1H),7.90(d,J=8.5Hz,1H),7.87-7.83(m,3H),7.70(t,J=8.0 Hz,1H),7.64-7.59(m,1H),7.48(t,J=7.7 Hz,2H),1.30(s,9H).

[0267] 13C NMR(100 MHz,CDCl3)δ193.6,162.9,147.8,146.5,136.2,136.1,132.5,131.8,130.4,129.5,128.8,128.0,127.7,127.0,126.5,83.0,26.4.

[0268] HRMS(ESI)m / z:Calcd for C 21 H 20 NO3 + [M+H] + :334.1438;found:334.1437.

[0269]

[0270] (3-benzoylquinolin-2-yl)(p-tolyl)methanone

[0271] 34.2 mg,63%yield.Yellow solid,(Flash column chromatography eluent,petroleumether / ethyl acetate=15 / 1,V / V).

[0272] 1 H NMR(400 MHz,Chloroform-d)δ8.40(s,1H),8.23(d,J=8.4 Hz,1H),7.98(d,J=8.2Hz,2H),7.93(d,J=8.2 Hz,1H),7.87(t,J=7.4 Hz,3H),7.72(t,J=7.5 Hz,1H),7.59(t,J=7.4Hz,1H),7.46(t,J=7.8 Hz,2H),7.28(d,J=8.2 Hz,2H),2.43(s,3H).

[0273] 13 C NMR(100 MHz,CDCl3)δ195.1,193.4,156.6,146.8,144.5,137.9,136.8,133.4,133.2,133.0,131.8,131.1,130.2,130.1,129.1,128.9,128.6,128.4,126.6,21.9.

[0274] HRMS(ESI)m / z:Calcd for C 24 H 18 NO2+ [M+H] + :352.1332;found:352.1331.

[0275]

[0276] (3-benzoylquinolin-2-yl)(4-chlorophenyl)methanone

[0277] 25.2 mg,41%yield.White solid,(Flash column chromatography eluent,petroleumether / ethyl acetate=15 / 1,V / V).

[0278] 1 H NMR(400 MHz,Chloroform-d)δ8.41(s,1H),8.22(d,J=8.4 Hz,1H),8.05(d,J=8.6Hz,2H),7.96-7.91(m,1H),7.88(t,J=7.0 Hz,3H),7.81(d,J=8.5 Hz,1H),7.74(t,J=7.5 Hz,1H),7.61(t,J=6.8 Hz,1H),7.50-7.42(m,3H).

[0279] 13 C NMR(100 MHz,CDCl3)δ194.0,191.4,154.9,145.7,139.0,137.1,135.6,133.0,132.6,131.9,131.3,130.9,129.1,129.0,128.11,128.08,128.0,127.68,127.65.

[0280] HRMS(ESI)m / z:Calcd for C 23 H 15 ClNO2 + [M+H] + :372.0786;found:372.0785.

[0281]

[0282] (6-isopropylquinoline-2,3-diyl)bis(phenylmethanone)

[0283] 36.8 mg,61%yield.Yellow oil,(Flash column chromatography eluent,petroleum ether / ethylacetate=20 / 1,V / V).

[0284] 1 H NMR(400 MHz,Chloroform-d)δ8.35(s,1H),8.16(d,J=8.6 Hz,1H),8.10-8.06(m,2H),7.89-7.86(m,2H),7.81-7.78(m,1H),7.72(d,J=1.6 Hz,1H),7.61-7.55(m,2H),7.48-7.43(m,4H),3.19-3.12(m,1H),1.38(d,J=6.9 Hz,6H).

[0285] 13 C NMR(100 MHz,CDCl3)δ194.2,192.7,154.5,149.0,144.7,136.6,135.8,134.7,132.41,132.35,131.9,130.9,129.9,129.0,128.9,127.7,127.6,127.3,123.5,33.2,22.7.

[0286] HRMS(ESI)m / z:Calcd for C 26 H 22 NO2 + [M+H] + :380.1645;found:380.1646.

[0287]

[0288] 1-phenylpyridazino[4,5-b]quinolin-4(3H)-one

[0289] 31.4 mg,58%yield.Yellow solid,(Directly extract).

[0290] 1H NMR(400 MHz,DMSO-d6)δ12.97(s,1H),8.79(s,1H),8.30(t,J=7.2 Hz,2H),8.03(t,J=7.6 Hz,1H),7.80(t,J=7.6 Hz,1H),7.71-7.69(m,2H),7.63-7.57(m,3H).

[0291] 13 C NMR(100 MHz,DMSO)δ158.8,149.4,146.9,143.7,137.0,135.2,133.3,130.1,130.0,129.9,129.7,129.5,129.21,129.16,123.2.

[0292] HRMS(ESI)m / z:Calcd for C 17 H 12 N3O1 + [M+H] + :274.0975;found:274.0974.

Claims

1. A method for preparing quinoline derivatives, characterized in that, The process includes the following steps: reacting an enaminoketone compound with an N-phenylglycine ester compound in a solvent under heating in the presence of an oxidant to generate a quinoline derivative; wherein the oxidant is selected from one or more of tert-butyl hydroperoxide, 2,3-dichloro-5,6-dicyanobenzoquinone, benzoyl peroxide, potassium permanganate, di-tert-butyl peroxide, diacetoxyiodobenzene, o-iodobenzoic acid, Dys-Martin oxidant, and potassium persulfate; the reaction temperature of the method is 50-100 degrees Celsius; wherein, The structures of enamine ketone compounds are shown in Formula I: ; The structures of N-phenylglycine ester compounds are shown in Formula II: ; The resulting quinoline derivative has the structure shown in formula (III): ; The quinoline derivative shown in formula (III) has any of the following structures: 。 2. The method for preparing quinoline derivatives according to claim 1, characterized in that, The molar ratio of the reaction is enamine ketone compound: N-phenylglycine ester compound: oxidant = 1:1:(1.5-3), and the reaction time is 1-3 hours.

3. The method for preparing quinoline derivatives according to claim 2, characterized in that, The molar ratio of the reaction was enamine ketone compound: N-phenylglycine ester compound: oxidant = 1:1:2, and the reaction time was 1.5 hours.

4. The method for preparing quinoline derivatives according to claim 3, characterized in that, The solvent is acetone, 1,4-dioxane, ethanol, or 1,2-dichloroethane.

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