Synthetic method of indoline and benzotriaza compound

Abstract

The invention discloses a synthesis method of indoline and benzotriaza compounds, and belongs to the field of organic synthesis. According to the invention, alpha-halogenated hydrazone and 2-aminochalcone are used as reactants, a ring closing alkali is added, and a reaction is carried out in an organic solvent at 0-60 DEG C for 2-24 hours to respectively obtain indoline as shown in a formula (I) or a benzotriaza compound as shown in a formula (II). According to the present invention, the alpha-halogenated hydrazone is adopted as the one-carbon synthon to participate in the cyclization reaction, such that the indoline derivative is constructed, and the benzotriaza compound is synthesized; the method is simple to operate and high in yield, and has excellent diastereoselectivity (gt; 19: 1). In addition, the invention also expands the range of the alpha-halogenated hydrazone participating in the [3 + 4] cyclization reaction as a triatomic synthon. # imgabs0 #

Description

Technical Field

[0001] The invention relates to a method for synthesizing indoline and benzotriazepine compounds, and belongs to the field of organic synthesis. Background Art

[0002] Nitrogen-containing heterocyclic compounds are widely present in natural products, such as vitamins, hormones, antibiotics and alkaloids, and play an important role in the physiological activities of organisms. Nitrogen-containing heterocyclic compounds are also widely present in active drug molecules and have been widely used in the pharmaceutical and pesticide industries. Therefore, it is of great significance to develop new synthetic methods for nitrogen-containing heterocyclic compounds.

[0003] α-Halogenated hydrazones are easy-to-prepare intermediates and are widely used in the construction of nitrogen-containing heterocyclic compounds. Usually, α-halogenated hydrazones can generate nitrile imines in situ under the action of bases. Nitrile imines are 1,3-dipoles, and thus participate in cyclization reactions as triatomic synthons to construct nitrogen-containing heterocyclic compounds. However, the current modes of α-halogenated hydrazones participating in cyclization reactions are all as triatomic synthons, mainly [3+2] cyclization reactions, which are used to construct five-membered nitrogen-containing heterocycles, while [3+3] and [3+4] cyclization reactions are rarely reported. In addition, α-halogenated hydrazones participating in cyclization reactions as other types of synthons have not been reported.

[0004] In 2005, Sibi's research group first reported the asymmetric 1,3-dipolar cycloaddition reaction involving α-halogenated hydrazone (Sibi, MP; Stanley, LM; Jasperse, CPAN entry to a chiral dihydropyrazole scaffold: enantioselective [3+2] cycloaddition of nitrile imines. J. Am. Chem. Soc., 2005, 127 (23): 8276-8277.). Under the action of Mg (II) / oxazoline ligand complex, the halogenated hydrazone was treated with DIPEA to generate nitrile imine, which then reacted with oxazolidinone compounds to obtain dihydropyrazole structure compounds with high enantioselectivity. The reaction has high yield and excellent enantioselectivity.

[0005]

[0006] In 2016, the Werz group reported the [3+3] cyclization reaction of α-halohydrazone and DA cyclopropane in the presence of imidazole and TiCl4 to obtain a series of tetrahydropyridazines. The reaction substrates have good applicability and have medium to excellent yields (Werz, DB; Garve, LKB; Petzold, M.; Jones, PG [3+3]-Cycloaddition of donor-acceptor cyclopropanes with nitrile imines generated in situ: access to tetrahydropyridazines. Org. Lett., 2016, 18(3): 564-567.).

[0007]

[0008] In 2018, Guo's group reported a [3+4] annulation reaction of aza-o-quinonemethides with arylcarbohydrazonoyl chlorides for synthesis of 2,3-dihydro-1H-benzo[e][1,2,4]triazepines under mild conditions, which gave rise to biologically active benzotriazepines. The reaction went through three consecutive steps: conjugate addition, intramolecular cyclization, and rearrangement, and the target product was obtained in moderate to excellent yields (Guo, HC; Guo, ZY; Jia, H.; Liu, HL; Wang, QJ; Huang, JXA [4+3] annulation reaction of aza-o-quinonemethides with arylcarbohydrazonoyl chlorides for synthesis of 2,3-dihydro-1H-benzo[e][1,2,4]triazepines. Org. Lett., 2018, 20(10): 2939-2943.).

[0009]

[0010] The construction of nitrogen-containing heterocyclic compounds using α-halohydrazone as raw materials has been widely developed. However, in the currently developed methods, the azomethine carbon atom of α-halohydrazone only exhibits nucleophilicity and participates in the cyclization reaction as a three-atom synthesis, while the electrophilicity of the azomethine carbon atom has never been reported. Therefore, the development of new reaction modes for α-halohydrazone is of great significance for the construction of nitrogen-containing heterocyclic compounds. Summary of the invention

[0011] In view of the above problems existing in the prior art, the object of the present invention is to provide a method for constructing nitrogen-containing heterocyclic compounds starting from α-halogenated hydrazones, which method has simple operation, high yield, and excellent chemical selectivity and diastereoselectivity.

[0012] The present invention uses α-halogenated hydrazone as a raw material, and reacts with 2-aminochalcone under the action of a ring-closing base to generate a hydrazone, at which time the carbon atom of azomethine shows electrophilicity, and then undergoes an intramolecular Michael addition reaction to obtain a nitrogen-containing heterocyclic compound. The intramolecular Michael addition reaction process can be regulated by regulating the nitrogen atom substituent of 2-aminochalcone, thereby realizing the synthesis of indoline and benzotriazepine nitrogen-containing heterocyclic compounds: 1) when a sulfonyl substituent is attached to the nitrogen atom, the carbon atom of azomethine has nucleophilicity, and an intramolecular Michael addition reaction occurs to obtain an indoline derivative; 2) when the nitrogen atom of 2-aminochalcone is -NH2, the sp of the hydrazone is 3 The hybridized nitrogen atom shows nucleophilicity and undergoes intramolecular aza-Michael addition reaction to give benzotriazepine derivatives.

[0013] In order to achieve the above-mentioned object of the invention, the technical solution adopted by the present invention is:

[0014] A method for synthesizing an indoline and a benzotriazepine compound comprises the following steps: using an α-halohydrazone and a 2-aminochalcone as reactants, adding a cyclizing base, and reacting in an organic solvent at 0-60° C. for 2-24 hours to obtain an indoline compound as shown in formula (I) or a benzotriazepine compound as shown in formula (II):

[0015]

[0016] The cyclization base includes but is not limited to triethylamine, diisopropylethylamine, 1,8-diazabicycloundec-7-ene, cesium carbonate, potassium tert-butoxide, sodium bicarbonate, etc.; the organic solvent includes but is not limited to dichloromethane, chloroform, 1,2-dichloroethane, acetonitrile, etc.

[0017] In terms of molar amount, the amount of the cyclizing base is 1-4 times that of 2-aminochalcone; and the amount of the α-halogenated hydrazone is 2 times that of 2-aminochalcone.

[0018] When the product is a compound of formula (I):

[0019] The chemical structural formula of the 2-aminochalcone is Where R 1 is selected from one of hydrogen, 5-methyl, 5-methoxy, 5-fluoro, 5-chloro, 5-bromo, 4-chloro, 4-bromo or 3-fluoro; R 2is selected from phenyl, 4-methylphenyl, 4-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 3-methylphenyl, 3-methoxyphenyl, 3-bromophenyl, 2-methylphenyl, 2-chlorophenyl, 2-furyl, 3-thienyl, 2-naphthyl, methyl, ethyl, n-butyl, cyclopropyl, methoxy or one of the substituents of formula (III),

[0020]

[0021] R 3 Selected from 4-methylphenylsulfonyl, 4-fluorophenylsulfonyl, 4-chlorophenylsulfonyl, 4-bromophenylsulfonyl, 4-nitrophenylsulfonyl, 4-trifluoromethylphenylsulfonyl, phenylsulfonyl, 2-naphthylsulfonyl, 2-thienylsulfonyl, cyclopropylsulfonyl.

[0022] The chemical structural formula of the α-halogenated hydrazone is Where R 4 It is selected from the group consisting of phenyl, 4-chlorophenyl, 4-bromophenyl, 4-methylphenyl, 4-methoxyphenyl, 3-chlorophenyl and 1-naphthyl.

[0023] In a preferred technical solution, the amount of the cyclizing base used is twice that of 2-aminochalcone in terms of molar amount.

[0024] In a preferred technical solution, the amount of the α-halogenated hydrazone is twice that of 2-aminochalcone in terms of molar amount.

[0025] In the preferred technical solution, the reaction temperature is 40°C and the reaction time is 6 hours.

[0026] In the above technical solution, after the reaction is completed, the product can be separated by simple column chromatography (the eluent is preferably petroleum ether: ethyl acetate = 15:1 to 10:1) to obtain the target product.

[0027] The above reaction process is as follows:

[0028]

[0029] When the product is a compound of formula (II):

[0030] The chemical structural formula of the 2-aminochalcone is Where R 1 is selected from the group consisting of hydrogen, 5-methoxy, 5-fluoro, 5-chloro, 4-methoxy, and 4-chloro; R 2is selected from phenyl, 4-methylphenyl, 4-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-trifluoromethylphenyl, 4-biphenyl, 3-chlorophenyl, 3-bromophenyl, 3-methoxyphenyl, 2-methoxyphenyl, 2-chlorophenyl, 3,4-dimethoxyphenyl, 2,4-dichlorophenyl, 1-naphthyl, 2-naphthyl, 2-furyl, 2-thienyl, methyl, tert-butyl, cyclopropyl, methoxy or one of the compounds of formula (IV):

[0031]

[0032] R 3 For hydrogen.

[0033] The chemical structural formula of the α-halogenated hydrazone is Where R 4 It is selected from the group consisting of phenyl, 4-chlorophenyl, 4-bromophenyl, 4-methylphenyl, 4-methoxyphenyl, 4-cyanophenyl, 4-nitrophenyl, 3-chlorophenyl, 2-fluorophenyl and 1-naphthyl.

[0034] In a preferred technical solution, the amount of the base used is twice that of 2-aminochalcone in terms of molar amount.

[0035] In a preferred technical solution, the amount of the α-halogenated hydrazone is twice that of 2-aminochalcone in terms of molar amount.

[0036] In the preferred technical solution, the reaction temperature is 25°C and the reaction time is 8h.

[0037] In the above technical solution, after the reaction is completed, the product can be separated by simple column chromatography (the eluent is preferably petroleum ether: ethyl acetate = 15:1 to 10:1) to obtain the target product.

[0038] The above reaction process is as follows:

[0039]

[0040] Due to the application of the above technical solution, the present invention has the following advantages compared with the prior art:

[0041] 1. The present invention realizes for the first time the use of α-halogenated hydrazone as a one-carbon synthon to participate in the cyclization reaction, constructs indoline derivatives, and synthesizes benzotriazepine compounds. The method is simple to operate, has a high yield, and has excellent diastereoselectivity (>19:1).

[0042] 2. The present invention expands the scope of α-halohydrazone as a three-atom synthon participating in the [3+4] cyclization reaction. DETAILED DESCRIPTION

[0043] The present invention will be further described below in conjunction with specific embodiments.

[0044] Embodiment 1:

[0045]

[0046] 2-aminochalcone 1a (37.7 mg, 0.10 mmol), α-halohydrazone 2a (39 mg, 0.20 mmol) and acetonitrile (1.0 ml) were added to the reaction flask in sequence, and finally triethylamine (20.2 mg, 0.20 mmol) was added, and the mixture was reacted at 40°C for 6 hours. After the reaction, the reaction solvent was dried and the target product 3a (40 mg) was obtained by column chromatography (the eluent is preferably petroleum ether: ethyl acetate = 15:1 to 10:1), with a yield of 75% and dr>19:1. The product 3a was analyzed, and the results are as follows: 1 H NMR (400MHz, CDCl3): δ7.96 (t, J=8.6Hz, 4H), 7.63 (t, J=7.2Hz, 1H), 7.54 (d, J= 8.0Hz,2H),7.48(t,J=7.4Hz,2H),7.38(t,J=6.9Hz,1H),7.30(d,J=8.7Hz,3H) ,7.25-7.23(m,1H),7.10(d,J=3.7Hz,2H),7.02(d,J=7.4Hz,1H),6.93-6.87(m ,1H),4.90(dd,J=9.9,5.9Hz,1H),3.41-3.29(m,2H),2.49(s,3H),2.39(s,3H); 13 C NMR (101MHz, CDCl3): δ206.0,197.8,150.2,144.0,140.7,136.7,136.2,133.5,131.8,129.6,128.9,128.82,128.77,128.6,128.3,128. 1,123.4,123.2,122.6,112.0,101.5,48.9,38.4,30.2,21.6;IR(neat):ν3853,3748,3630,2928,1697,1536,1512,1462,1267,754,672cm -1 ; HRMS (ESI): m / z [MH] - calcd.for C 31 H 26 N3O4S:536.1650; found:536.1645.

[0047] Embodiment 2:

[0048]

[0049] 2-aminochalcone 1b (39.1 mg, 0.10 mmol), α-halohydrazone 2a (39 mg, 0.20 mmol) and acetonitrile (1.0 ml) were added to the reaction flask in sequence, and finally diisopropylethylamine (25.9 mg, 0.20 mmol) was added, and the mixture was reacted at 40°C for 12 hours. After the reaction, the reaction solvent was dried and the target product 3b (40 mg) was obtained by column chromatography (the eluent is preferably petroleum ether: ethyl acetate = 15:1 to 10:1), with a yield of 73% and dr>19:1. The product 3b was analyzed, and the results are as follows: 1 H NMR (400MHz, CDCl3): δ7.96(t,J=7.8Hz,4H),7.64(t,J=7.5Hz,1H),7.54(d, J=8.0Hz,2H),7.49(t,J=7.6Hz,2H),7.39(t,J=6.8Hz,1H),7.30(d,J=7.8Hz ,4H),7.01(d,J=8.2Hz,1H),6.91(d,J=8.2Hz,1H),6.83(s,1H),4.89(dd,J= 10.0,5.7Hz,1H),3.41-3.28(m,2H),2.48(s,3H),2.39(s,3H),2.21(s,3H); 13 C NMR (101MHz, CDCl3): δ205.9,197.9,150.2,143.8,138.4,136.8,136.2,133.5,132.3,131.7,129.6,128.95,128.90,128.8,128.2(2C) ,128.1,123.9,123.4,111.8,101.6,48.8,38.4,30.1,21.5,20.8;IR(neat):ν3856,3745,3623,2929,1653,1541,1262,1031,754,671cm –1 ; HRMS (ESI): m / z [MH] - calcd.forC 32 H 28 N3O4S:550.1806; found:550.1802.

[0050] Embodiment 3:

[0051]

[0052] 2-aminochalcone 1c (40.7 mg, 0.10 mmol), α-halohydrazone 2a (39 mg, 0.20 mmol) and dichloromethane (1.0 ml) were added to the reaction flask in sequence, and finally triethylamine (20.2 mg, 0.20 mmol) was added, and the mixture was reacted at 40°C for 24 hours. After the reaction, the reaction solvent was dried and the target product 3c (30 mg) was obtained by column chromatography (the eluent is preferably petroleum ether: ethyl acetate = 15:1 to 10:1), with a yield of 53% and dr>19:1. The product 3c was analyzed, and the results are as follows: 1 H NMR (400MHz, CDCl3): δ7.95(t,J=9.6Hz,4H),7.64(t,J=6.9Hz,1H),7.54(d,J=7.6Hz,2H),7.48(t,J=7.5Hz,2H),7.39(t,J=6.8Hz,1H),7.30- 7.27(m,4H),7.06(d,J=8.7Hz,1H),6.65-6.60(m,2H),4.89(dd,J=10.6 ,4.6Hz,1H),3.69(s,3H),3.40-3.23(m,2H),2.47(s,3H),2.40(s,3H); 13 C NMR (101MHz, CDCl3): δ205.6,197.7,155.9,150.2,143.8,136.8,136.2,134.3,133.5,131.8,130.6,129.6,128.9,128.8,128.2,128.1 ,123.3,112.9,112.6,110.1,101.6,55.7,48.7,38.4,30.0,21.6;IR(neat):ν3832,3747,3684,2710,1701,1518,1113,1057,957,754cm –1 ; HRMS (ESI): m / z [MH] - calcd.for C 32 H 28 N3O5S:566.1755; found:566.1751.

[0053] Embodiment 4:

[0054]

[0055] 2-aminochalcone 1d (39.5 mg, 0.10 mmol), α-halohydrazone 2a (39 mg, 0.20 mmol) and acetonitrile (1.0 ml) were added to the reaction flask in sequence, and finally triethylamine (20.2 mg, 0.20 mmol) was added, and the mixture was reacted at 0°C for 24 hours. After the reaction, the reaction solvent was dried and the target product 3d (42 mg) was obtained by column chromatography (the eluent is preferably petroleum ether: ethyl acetate = 15:1 to 10:1), with a yield of 75% and dr>19:1. The product 3d was analyzed, and the results are as follows: 1 H NMR (400MHz, CDCl3): δ7.94(d,J=6.4Hz,4H),7.65(t,J=7.5Hz,1H),7.56(d,J=7.6Hz,2H),7.50(t,J=7.7Hz,2H),7.41(t,J=7.5Hz,1H),7. 32-7.27(m,4H),7.06(dd,J=8.8,4.3Hz,1H),6.82-6.74(m,2H),4.89(dd,J=10.9,4.8Hz,1H),3.43-3.24(m,2H),2.49(s,3H),2.40(s,3H); 13 C NMR (101MHz, CDCl3): δ205.5,197.4,160.2(d,J C-F =242.2Hz),150.1,144.1,136.7(d,J C-F =1.9Hz),136.5,136.0,133.6,131.9,130.9(d,J C-F =8.0Hz),129.6,129.0,128.8,128.2,128.1,123.3,115.0(d,J C-F =23.3Hz),112.7(d,J C-F =8.4Hz),111.1(d,J C-F =24.9Hz),101.8,48.6,38.1,30.1,21.5; IR(neat):ν3835,3750,2998,2764,1694,1271,1029,758,712,676cm –1 ; HRMS (ESI): m / z [MH] - calcd.for C 31 H 25 N3O4FS:554.1555; found:554.1545.

[0056] Embodiment 5:

[0057]

[0058] 2-aminochalcone 1e (41.1 mg, 0.10 mmol), α-halohydrazone 2a (39 mg, 0.20 mmol) and acetonitrile (1.0 ml) were added to the reaction flask in sequence, and finally triethylamine (20.2 mg, 0.20 mmol) was added, and the mixture was reacted at 60°C for 2 hours. After the reaction, the reaction solvent was dried and the target product 3e (46 mg) was obtained by column chromatography (the eluent is preferably petroleum ether: ethyl acetate = 15:1 to 10:1), with a yield of 80% and dr>19:1. The product 3e was analyzed, and the results are as follows: 1 H NMR (400MHz, CDCl3): δ7.95-7.92(m,4H),7.65(t,J=7.2Hz,1H),7.56(d,J=7.7Hz,2H),7.50(t,J=7.6Hz,2H),7.41(t,J=7.1Hz,1 H),7.34-7.27(m,4H),7.12(s,1H),6.93-6.87(m,2H),4.83(dd,J=10.1,5.3Hz,1H),3.39-3.26(m,2H),2.49(s,3H),2.41(s,3H); 13 C NMR (101MHz, CDCl3): δ205.5,197.6,150.1,144.4,141.8,136.21,136.19,134.1,133.6,131.9,129.7,129.0,128.8,128.2,128.1,12 7.5,124.0,123.4,122.7,112.5,101.9,48.4,38.1,30.2,21.6;IR(neat):ν3858,3754,3685,2863,1702,1558,1123,1029,749,680cm –1 ; HRMS (ESI): m / z [MH] - calcd.for C 31 H 25 N3O4ClS:570.1260; found:570.1256.

[0059] Embodiment 6:

[0060]

[0061] 2-aminochalcone 1f (41.1 mg, 0.10 mmol), α-halohydrazone 2a (19.5 mg, 0.10 mmol) and acetonitrile (1.0 ml) were added to the reaction flask in sequence, and finally triethylamine (20.2 mg, 0.20 mmol) was added, and the mixture was reacted at 40°C for 6 hours. After the reaction, the reaction solvent was dried and the target product 3f (44 mg) was obtained by column chromatography (the eluent is preferably petroleum ether: ethyl acetate = 15:1-10:1), with a yield of 80% and dr>19:1. The product 3f was analyzed, and the results are as follows: 1 H NMR (400MHz, CDCl3): δ8.02(d,J=7.2Hz,2H),7.95(d,J=7.2Hz,2H),7.65-7.5 8(m,3H),7.50(t,J=7.9Hz,2H),7.41(t,J=7.4Hz,1H),7.31-7.27(m,4H),6.90 -6.80(m,3H),4.94(dd,J=10.7,4.7Hz,1H),3.46-3.29(m,2H),2.52(s,3H),2.41(s,3H); 13 C NMR (101MHz, CDCl3): δ206.1,197.4,150.1,149.1(d,J C-F =249.7Hz),143.7,137.4(d,J C-F =2.7Hz),136.1,133.6,132.6(d,J C-F =3.2Hz),131.9,129.4,129.0(d,J C-F =18.1Hz),128.3,128.2,128.1,123.9,123.8,123.4,118.9,118.9,117.3(d,J C-F =21.5Hz),102.1,49.0,38.3,30.1,21.6; IR(neat):ν3947,3668,3303,2936,2074,1726,1431,1143,1070,941,770cm –1 ; HRMS (ESI): m / z [MH] - calcd.for C 31 H 25 N3O4FS:554.1555; found:554.1545.

[0062] Embodiment 7:

[0063]

[0064] 2-aminochalcone 1g (39.1mg, 0.10mmol) and α-halogenated hydrazone 2a (78mg, 0.40mmol) and acetonitrile (1.0ml) were added to the reaction flask in sequence, and finally triethylamine (20.2mg, 0.20mmol) was added, and the mixture was reacted at 40°C for 6 hours. After the reaction, the reaction solvent was dried and the target product 3g (41mg) was obtained by column chromatography (the eluent is preferably petroleum ether: ethyl acetate = 15:1-10:1), with a yield of 75% and dr>19:1. The product 3g was analyzed, and the results are as follows: 1 H NMR (400MHz, CDCl3): δ7.94(d,J=8.3Hz,2H),7.81(d,J=8.2Hz,2H),7.53(d,J=8.5Hz,2H),7.36(t,J=7.3Hz,1H),7.27-7.24(m,4H),7.22(s,2H),7. 07(d,J=3.9Hz,2H),6.98(d,J=7.3Hz,1H),6.90-6.85(m,1H),4.86(dd,J= 9.9,5.8Hz,1H),3.36-3.24(m,2H),2.46(s,3H),2.41(s,3H),2.36(s,3H); 13 C NMR (101MHz, CDCl3): δ205.9,197.4,150.2,144.4,143.9,140.8,136.7,133.8,131.7,129.6,129.4,128.9(2C),128.5,128.3,128.2,1 23.4,123.2,122.6,112.0,101.6,49.0,38.2,30.2,21.7,21.5;IR(neat):ν3865,3686,3578,3376,2937,1739,1658,1564,1265,767cm -1 ; HRMS (ESI): m / z [MH] - calcd.for C 32 H 28 N3O4S:550.1806; found:550.1802.

[0065] Embodiment 8:

[0066]

[0067] 2-aminochalcone 1h (45.6 mg, 0.10 mmol), α-halogenated hydrazone 2a (39 mg, 0.20 mmol) and acetonitrile (1.0 ml) were added to the reaction flask in sequence, and finally cesium carbonate (65 mg, 0.20 mmol) was added, and the mixture was reacted at 40°C for 6 hours. After the reaction, the reaction solvent was dried and the target product 3h (11 mg) was obtained by column chromatography (the eluent is preferably petroleum ether: ethyl acetate = 15:1-10:1), with a yield of 18% and dr>19:1. The product 3h was analyzed, and the results are as follows: 1 H NMR (400MHz, CDCl3): δ7.96(d,J=7.9Hz,2H),7.80(d,J=8.2Hz,2H),7.61(d,J=8.0Hz,2H),7.53(d,J=8.0Hz,2H),7.42(t,J=7.1Hz,1H),7.32-7 .29(m,4H),7.12(d,J=3.9Hz,2H),7.02(d,J=7.5Hz,1H),6.94-6.88(m, 1H),4.89(t,J=7.7Hz,1H),3.36-3.27(m,2H),2.48(s,3H),2.40(s,3H); 13 C NMR (101MHz, CDCl3): δ205.9,196.8,150.1,144.0,140.7,136.6,134.8,132.1,131.9,129.6(2C),129.0,128.8,128.63,128.57,128 .2,123.3,123.1,122.7,112.0,101.4,48.8,38.3,30.1,21.6;IR(neat):ν3860,3749,3633,2930,1653,1263,1097,1032,753,669cm -1 ; HRMS (ESI): m / z [MH] - calcd.for C 31 H 25 N3O4BrS:614.0755; found:614.0747.

[0068] Embodiment 9:

[0069]

[0070] 2-aminochalcone 1i (40.7 mg, 0.10 mmol), α-halohydrazone 2a (39 mg, 0.20 mmol) and acetonitrile (1.0 ml) were added to the reaction flask in sequence, and finally triethylamine (20.2 mg, 0.20 mmol) was added, and the mixture was reacted at 40°C for 6 hours. After the reaction, the reaction solvent was dried and the target product 3i (40 mg) was obtained by column chromatography (the eluent is preferably petroleum ether: ethyl acetate = 15:1-10:1), with a yield of 70% and dr>19:1. The product 3i was analyzed, and the results are as follows: 1 H NMR (400MHz, CDCl3): δ7.97(d,J=7.8Hz,2H),7.57(d,J=7.7Hz,2H),7.49(d,J=11.9Hz,2H),7.40-7.34(m,2H),7.31(d,J=7.7Hz,4H),7.17(d,J=8.0H z,1H),7.11(s,2H),7.03(d,J=7.2Hz,1H),6.93-6.91(m,1H),4.90(dd,J= 9.9,5.4Hz,1H),3.83(s,3H),3.41-3.29(m,2H),2.50(s,3H),2.39(s,3H); 13 C NMR (101MHz, CDCl3): δ205.9,197.6,160.0,150.2,144.0,140.8,137.5, 136.7,131.8,129.7,129.6,128.9,128.8,128.6,128.3,123.4,123.2,1 22.7,120.7,120.1,112.2,112.0,101.5,55.5,48.9,38.4,30.2,21.5; I R(neat):ν3866,3639,3482,2928,1463,1267,1068,1031,880,769,697cm –1 ; HRMS (ESI): m / z [MH] - calcd.for C 32 H 28 N3O5S:566.1755; found:566.1751.

[0071] Embodiment 10:

[0072]

[0073] 2-aminochalcone 1j (41.1 mg, 0.10 mmol), α-halohydrazone 2a (39 mg, 0.20 mmol) and acetonitrile (1.0 ml) were added to the reaction flask in sequence, and finally triethylamine (20.2 mg, 0.20 mmol) was added, and the mixture was reacted at 40°C for 6 hours. After the reaction, the reaction solvent was dried and the target product 3j (40 mg) was obtained by column chromatography (the eluent is preferably petroleum ether: ethyl acetate = 15:1 to 10:1), with a yield of 70% and dr>19:1. The product 3j was analyzed, and the results are as follows: 1 H NMR (400MHz, CDCl3): δ7.97(d,J=7.9Hz,2H),7.64(d,J=6.6Hz,3H),7.46(d,J=3.4Hz,2H),7.41(d,J=7.4Hz,1H),7.35(dd,J=17.8,7.6Hz,5H),7.11(d ,J=3.3Hz,2H),7.03(d,J=7.4Hz,1H),6.93-6.90(m,1H),4.86(dd,J=10.8, 3.8Hz,1H),3.57-3.51(m,1H),3.35-3.28(m,1H),2.58(s,3H),2.39(s,3H); 13 C NMR (101MHz, CDCl3): δ205.8,199.8,150.3,144.0,140.7,137.6,136.6,132.5,131.8,131.7,131.0,130.0,129.6,129.0,128.6,128.5,128.2 ,127.0,123.3,123.2,122.7,112.0,101.5,48.8,42.7,30.3,21.5;IR( neat):ν3833,3757,3687,2864,2175,1830,1463,1115,1045,813,718cm –1 ; HRMS (ESI): m / z [MH] - calcd.for C 31 H 25 N3O4ClS:570.1260; found:570.1256.

[0074] Embodiment 11:

[0075]

[0076] 2-Aminochalcone 1j (36.7 mg, 0.10 mmol), α-halohydrazone 2a (39 mg, 0.20 mmol) and acetonitrile (1.0 ml) were added to the reaction flask in sequence, and finally triethylamine (20.2 mg, 0.20 mmol) was added, and the mixture was reacted at 40°C for 6 hours. After the reaction, the reaction solvent was dried and the target product 3k (41 mg) was obtained by column chromatography (the eluent is preferably petroleum ether: ethyl acetate = 15:1-10:1), with a yield of 78% and dr>19:1. The product 3k was analyzed, and the results are as follows: 1 H NMR (400MHz, CDCl3): δ7.96 (d, J = 7.7Hz, 2H), 7.60 (d, J = 7.6Hz, 2H), 7.54 (s, 1H), 7.43-7.39 (m, 1H), 7.36 (d, J = 6.9Hz, 2H), 7.30 (d, J = 7.7Hz, 2H), 7.20(s,1H),7.10(s,2H),7.01(d,J=7.4Hz,1H),6.91(s,1H),6.57(s,1H ),4.86(t,J=7.6Hz,1H),3.24(d,J=7.7Hz,2H),2.50(s,3H),2.39(s,3H); 13 C NMR (101MHz, CDCl3): δ205.9,186.8,152.1,150.3,146.6,144.0,140.7,136.7,131.8,129.6,129.0,128.7,128.6,128.2,123.3,123.2 ,122.7,117.4,112.5,111.9,101.5,48.3,38.0,30.2,21.5;IR(neat):ν3748,3686,3621,3533,2863,2173,1506,1114,1068,749,669cm –1 ; HRMS (ESI): m / z [MH] - calcd.for C 29 H 24 N3O5S:526.1442; found:526.1440.

[0077] Embodiment 12:

[0078]

[0079] 2-aminochalcone 1l (31.5 mg, 0.10 mmol), α-halohydrazone 2a (39 mg, 0.20 mmol), and acetonitrile (1.0 ml) were added to the reaction flask in sequence, and finally 1,8-diazabicycloundec-7-ene (30.4 mg, 0.20 mmol) was added, and the mixture was reacted at 40°C for 6 hours. After the reaction, the reaction solvent was dried and the target product 3l (32 mg) was obtained by column chromatography (the eluent is preferably petroleum ether: ethyl acetate = 15:1 to 10:1), with a yield of 68% and dr>19:1. The product 3l was analyzed, and the results are as follows: 1 H NMR (400MHz, CDCl3): δ7.94(d,J=8.3Hz,2H),7.81-7.77(m,2H),7.49-7.48(m,3H),7.29(d,J=8.3Hz,2H),7.09(d,J=3.4Hz,2H),6.92-6.8 6(m,2H),4.65(dd,J=10.9,4.7Hz,1H),2.97(dd,J=18.6,4.7Hz,1H),2.80(dd,J=18.6,11.0Hz,1H),2.51(s,3H),2.38(s,3H),2.23(s,3H); 13 C NMR (101MHz, CDCl3): δ206.1,205.8,150.4,144.0,140.6,136.6,131.9,129.6,129.2,128.51,128.49,128.2,123.2,123.0,1 22.6,111.9,101.6,48.4,42.9,30.3,29.6,21.5;IR(neat):ν3452,3329,3146,2866,2520,1531,1360,1254,1107,806,679cm –1 ; HRMS (ESI): m / z [MH] - calcd.for C 26 H 24 N3O4S:474.1493; found:474.1489.

[0080] Embodiment 13:

[0081]

[0082] 2-aminochalcone 1m (34.1 mg, 0.10 mmol), α-halohydrazone 2a (39 mg, 0.20 mmol) and acetonitrile (1.0 ml) were added to the reaction flask in sequence, and potassium tert-butoxide (22.4 mg, 0.20 mmol) was added at last, and the mixture was reacted at 40°C for 6 hours. After the reaction, the reaction solvent was dried and the target product 3m (7.5 mg) was obtained by column chromatography (the eluent was preferably petroleum ether: ethyl acetate = 15:1-10:1), with a yield of 15% and dr>19:1. The product 3m was analyzed, and the results were as follows: 1 H NMR (400MHz, CDCl3): δ7.96-7.93(m,2H),7.86-7.83(m,2H),7.50-7.46(m,3H),7.29(d, J=8.6Hz,2H),7.09-7.06(m,2H),6.95-6.92(m,1H),6.90-6.86(m,1H),4.69(dd,J=11.0 ,4.7Hz,1H),3.13(dd,J=18.4,4.7Hz,1H),2.93(dd,J=18.7,11.1Hz,1H),2.47(s,3H),2 .38(s,3H),1.98-1.92(m,1H),1.21-1.14(m,2H),1.04-0.94(m,2H),0.90-0.83(m,1H); 13 CNMR (101MHz, CDCl3): δ208.3,205.9,150.4,143.9,140.6,136.6,131.8,129.6,129.1,128.6,128.4,128.2,123.4,123.1,122.6, 111.8,101.5,48.5,42.8,30.3,21.5,20.3,11.4,11.2;IR(neat):ν3949,3806,3620,3380,2932,1728,1142,1047,879,740,657cm –1 ; HRMS (ESI): m / z [MH] - calcd.for C 28 H 26 N3O4S:500.1650; found:500.1642.

[0083] Embodiment 14:

[0084]

[0085] 2-aminochalcone 1n (38.6 mg, 0.10 mmol), α-halohydrazone 2a (39 mg, 0.20 mmol) and acetonitrile (1.0 ml) were added to the reaction flask in sequence, and finally triethylamine (20.2 mg, 0.20 mmol) was added, and the mixture was reacted at 40°C for 6 hours. After the reaction, the reaction solvent was dried and the target product 3n (26 mg) was obtained by column chromatography (the eluent is preferably petroleum ether: ethyl acetate = 15:1-10:1), with a yield of 48% and dr>19:1. The product 3n was analyzed, and the results are as follows: 1 H NMR (400MHz, CDCl3): δ7.95 (d, J = 8.2Hz, 2H), 7.75-7.74 (m, 2H), 7.47-7.46 (m, 3H ),7.30(d,J=8.1Hz,2H),7.11-7.08(m,2H),7.03(d,J=7.5Hz,1H),6.92-6.88(m, 1H),4.73(dd,J=10.4,4.6Hz,1H),4.48-4.37(m,2H),4.09(t,J=8.0Hz,2H),3.49 (dd,J=18.7,10.5Hz,1H),3.34(dd,J=18.7,4.5Hz,1H),2.54(s,3H),2.39(s,3H); 13 C NMR (101MHz, CDCl3): δ205.5,171.4,153.3,150.7,144.0,140.6,136.7,131.9,129.6,129.1,128.6,128.21,128.17,123.6,123. 1,122.8,112.0,101.6,62.2,48.7,42.5,35.0,30.3,21.5;IR(neat):ν3866,3630,1705,1612,1555,1512,1462,1367,754,672cm –1 ; HRMS (ESI): m / z [MH] - calcd.forC 28 H 27 N4O6S:547.1657; found:547.1646.

[0086] Embodiment 15:

[0087]

[0088] 2-aminochalcone 1o (36.3 mg, 0.10 mmol), α-halohydrazone 2a (39 mg, 0.20 mmol) and acetonitrile (1.0 ml) were added to the reaction flask in sequence, and finally triethylamine (20.2 mg, 0.20 mmol) was added, and the mixture was reacted at 40°C for 6 hours. After the reaction, the reaction solvent was dried and the target product 3o (25 mg) was obtained by column chromatography (the eluent is preferably petroleum ether: ethyl acetate = 15:1-10:1), with a yield of 68% and dr>19:1. The product 3o was analyzed, and the results are as follows: 1 H NMR (400MHz, CDCl3): δ8.11(d,J=7.0Hz,2H),7.95(d,J=7.2Hz,2H),7.65(t,J=7.4Hz,1H),7.57-7.46(m,7H),7.40(t,J=7.4Hz,1H),7.30(d ,J=7.9Hz,2H),7.12(d,J=4.0Hz,2H),7.04(d,J=7.4Hz,1H),6.96-6.89(m,1H),4.97(dd,J=9.7,6.2Hz,1H),3.44-3.32(m,2H),2.51(s,3H); 13 C NMR (101MHz, CDCl3): δ205.9,197.8,150.1,140.7,139.7,136.2,133.5,133.1,131.8,128.97,128.95,128.81,128.78,128.6,12 8.2,128.1,123.4,123.2,122.8,112.0,101.6,48.9,38.4,30.2;IR(neat):ν3876,3609,3582,2931,2586,1428,1004,793,706cm –1 ; HRMS (ESI): m / z [MH] - calcd.for C 30 H 24 N3O4S:522.1493; found:522.1484.

[0089] Embodiment 16:

[0090]

[0091] 2-aminochalcone 1p (44.2 mg, 0.10 mmol), α-halohydrazone 2a (39 mg, 0.20 mmol) and acetonitrile (1.0 ml) were added to the reaction flask in sequence, and finally triethylamine (20.2 mg, 0.20 mmol) was added, and the mixture was reacted at 40°C for 6 hours. After the reaction, the reaction solvent was dried and the target product 3p (46 mg) was obtained by column chromatography (the eluent is preferably petroleum ether: ethyl acetate = 15:1 to 10:1), with a yield of 77% and dr>19:1. The product 3p was analyzed, and the results are as follows: 1 H NMR (400MHz, CDCl3): δ7.98-7.94(m,4H),7.67-7.62(m,3H),7.55(d,J=7.2Hz,2H),7.51(t,J=8.1Hz,2H),7.40(t,J=7.4Hz,1H) ,7.30-7.26(m,2H),7.15-7.11(m,1H),7.09-7.04(m,2H),6.97-6.93(m,1H),4.91-4.86(m,1H),3.45-3.35(m,2H),2.49(s,3H); 13 C NMR (101MHz, CDCl3): δ205.9,197.8,150.1,140.3,138.7,136.1,133.6,132.2,131.9,129.8,129.0,128.9,128.8,128.6,128.3,1 28.1,123.4(2C),123.0,111.9,101.7,48.9,38.3,30.2;IR(neat):ν3947,3881,3735,3614,2933,1733,1281,1070,998,773,667cm –1 ; HRMS (ESI): m / z [MH] - calcd.for C 30 H 23 N3O4BrS:600.0598; found:600.0594.

[0092] Embodiment 17:

[0093]

[0094] 2-aminochalcone 1a (37.7 mg, 0.10 mmol), α-halohydrazone 2b (42 mg, 0.20 mmol) and acetonitrile (1.0 ml) were added to the reaction flask in sequence, and finally triethylamine (20.2 mg, 0.20 mmol) was added, and the mixture was reacted at 40°C for 6 hours. After the reaction, the reaction solvent was dried and the target product 3q (42 mg) was obtained by column chromatography (the eluent is preferably petroleum ether: ethyl acetate = 15:1 to 10:1), with a yield of 76% and dr>19:1. The product 3q was analyzed, and the results are as follows: 1 H NMR (400MHz, CDCl3): δ7.97(t,J=8.7Hz,4H),7.65(t,J=7.2Hz,1H),7.50-7.42(m,4H),7.31(d,J=8.0Hz,2H),7.11(d,J=3.8Hz,2H),7.07(d,J =8.0Hz,2H),7.03(d,J=7.4Hz,1H),6.93-6.89(m,1H),4.90(dd,J=10.4 ,5.1Hz,1H),3.42-3.29(m,2H),2.48(s,3H),2.40(s,3H),2.34(s,3H); 13 C NMR (101MHz, CDCl3): δ206.2,197.9,148.4,143.9,142.4,140.8,136.8,136.3,133.5,129.6,129.5,129.0,128.8,128.5,128.3,128.1,12 3.4,123.2,122.6,111.9,101.5,48.9,38.4,30.2,21.5,21.4;IR(neat):ν3940,3811,3754,2929,1700,1662,1541,1456,1070,755,670cm –1 ; HRMS (ESI): m / z [MH] - calcd.for C 32 H 28 N3O4S:550.1806; found:550.1802.

[0095] Embodiment 18:

[0096]

[0097] 2-aminochalcone 1a (37.7 mg, 0.10 mmol), α-halohydrazone 2c (49 mg, 0.20 mmol) and acetonitrile (1.0 ml) were added to the reaction flask in sequence, and finally triethylamine (20.2 mg, 0.20 mmol) was added, and the mixture was reacted at 40°C for 6 hours. After the reaction, the reaction solvent was dried and the target product 3r (32 mg) was obtained by column chromatography (the eluent is preferably petroleum ether: ethyl acetate = 15:1 to 10:1), with a yield of 55% and dr>19:1. The product 3r was analyzed, and the results are as follows: 1 H NMR (400MHz, CDCl3): δ9.14(d,J=8.5Hz,1H),8.03(d,J=8.3Hz,2H),7.96(d,J=8.4Hz,2H),7.90 -7.88(m,1H),7.84(d,J=8.2Hz,1H),7.65(t,J=8.2Hz,2H),7.55(t,J=8.0Hz,1H),7.49(t,J=7. 8Hz,2H),7.32(d,J=8.2Hz,2H),7.27-7.25(m,1H),7.17-7.13(m,3H),7.03(d,J=7.5Hz,1H),6. 94(t,J=7.4Hz,1H),4.98(dd,J=10.6,5.2Hz,1H),3.49-3.35(m,2H),2.57(s,3H),2.39(s,3H); 13 C NMR (101MHz, CDCl3): δ205.9,198.0,145.5,144.0,140.7,136.5,134.3,136.2 ,134.3,133.5,132.3,129.6,128.82,128.77,128.6,128.3,128.2,127.6,127. 4,126.6,124.8,124.5,123.2,122.7,112.1,112.0,101.9,49.4,38.3,30.5,21 .5;IR(neat):ν3844,3754,3658,2924,2651,1653,1262,1071,1028,753,674cm –1 ; HRMS (ESI): m / z [MH] - calcd.for C 35 H 28 N3O4S:586.1806; found:586.1802.

[0098] Embodiment 19:

[0099]

[0100] 2-aminochalcone 4a (22.3 mg, 0.10 mmol), α-halohydrazone 2a (39 mg, 0.20 mmol) and acetonitrile (1.0 ml) were added to the reaction flask in sequence, and finally triethylamine (20.2 mg, 0.20 mmol) was added, and the mixture was reacted at 25°C for 8 hours. After the reaction, the reaction solvent was dried and the target product 5a (35 mg) was obtained by column chromatography (the eluent is preferably petroleum ether: ethyl acetate = 15:1 to 10:1), with a yield of 90%. The product 5a was analyzed, and the results are as follows: 1 H NMR (400MHz, CDCl3): δ7.87(s,1H),7.78(d,J=7.4Hz,2H),7.52-7.46(m,3H),7.37(t,J=15.7Hz,4H),7.32(d,J=7.4Hz,1H),7.16(t,J=7.6Hz,1H ),7.05(t,J=7.2Hz,1H),6.84-6.79(m,2H),5.90(dd,J=9.6,3.0Hz,1H),3.87(dd,J=16.7,9.6Hz,1H),3.39(dd,J=16.7,3.1Hz,1H),2.63(s,3H); 13 CNMR (101MHz, CDCl3): δ196.7,194.3,148.7,140.0,136.4,134.5,133.3,130.0,129.09,129.06,128.8,128.5,128.0,1 22.2,120.8,118.4,117.4,64.6,40.8,23.9;IR(neat):ν3941,3427,3031,2635,2558,1331,1258,1108,1013,748,653cm –1 ; HRMS (ESI): m / z [MH] - calcd.for C 24 H 20 N3O2:382.1559; found:382.1561.

[0101] Embodiment 20:

[0102]

[0103] 2-aminochalcone 4b (25.3 mg, 0.10 mmol), α-halohydrazone 2a (39 mg, 0.20 mmol) and acetonitrile (1.0 ml) were added to the reaction flask in sequence, and finally diisopropylethylamine (25.9 mg, 0.20 mmol) was added, and the mixture was reacted at 25°C for 24 hours. After the reaction, the reaction solvent was dried and the target product 5b (41 mg) was obtained by column chromatography (the eluent was preferably petroleum ether: ethyl acetate = 15:1 to 10:1), with a yield of 99%. The product 5b was analyzed, and the results were as follows: 1 H NMR (400MHz, CDCl3): δ7.79-7.72(m,3H),7.52-7.35(m,7H),7.02(s,1H),6.88(s,1H),6.72-6.69(m,2 H),5.81(s,1H),3.88(dd,J=16.7,9.5Hz,1H),3.76(s,3H),3.40(dd,J=16.7,2.6Hz,1H),2.61(s,3H); 13 C NMR (101MHz, CDCl3): δ196.7,194.4,153.6,148.8,136.5,135.1,133.4,133.3,130.0,129.1,128.5,128.0,122.1,119 .5,117.4,115.0,114.7,64.5,55.6,40.7,23.9;IR(neat):ν3892,3741,3357,2926,1658,1503,1269,1022,757,683cm –1 ; HRMS (ESI): m / z [MH] - calcd.for C 25 H 22 N3O3:412.1667; found:412.1660.

[0104] Embodiment 21:

[0105]

[0106] 2-aminochalcone 4c (30.2 mg, 0.10 mmol), α-halohydrazone 2a (39 mg, 0.20 mmol) and dichloromethane (1.0 ml) were added to the reaction flask in sequence, and finally triethylamine (20.2 mg, 0.20 mmol) was added, and the mixture was reacted at 0°C for 24 hours. After the reaction, the reaction solvent was dried and the target product 5c (37 mg) was obtained by column chromatography (the eluent was preferably petroleum ether: ethyl acetate = 15:1 to 10:1), with a yield of 81%. The product 5c was analyzed, and the results were as follows: 1H NMR (400MHz, CDCl3): δ7.86 (s, 1H), 7.78 (d, J = 8.5Hz, 2H), 7.54 (t, J = 7.4Hz, 1H), 7.44-7.34 (m, 6H), 7.20 (d, J = 8.1Hz, 1H), 7.06 (t, J = 7.2Hz, 1H), 6.97(d,J=1.8Hz,1H), 6.94(d,J=8.0Hz,1H), 5.86(dd,J=9.8,2.9Hz,1H), 3.84(dd,J=17.0,9.8Hz,1H), 3.36(dd,J=17.0,2.9Hz,1H), 2.61(s,3H); 13 C NMR (101MHz, CDCl3): δ196.4,194.0,148.4,141.4,136.3,133.8,133.5,131.6,129.2,128.6,128.0,127.8,123.6,122 .6,122.5,121.1,117.6,64.1,40.6,23.9;IR(neat):ν3761,3453,3328,2963,2737,1329,1286,1162,1008,731,644cm –1 ; HRMS (ESI): m / z [MH] - calcd.for C 24 H 19 N3O2Br:460.0666; found:460.0662.

[0107] Embodiment 22:

[0108]

[0109] 2-aminochalcone 4d (25.7 mg, 0.10 mmol), α-halohydrazone 2a (39 mg, 0.20 mmol) and acetonitrile (1.0 ml) were added to the reaction flask in sequence, and finally triethylamine (20.2 mg, 0.20 mmol) was added, and the mixture was reacted at 40°C for 4 hours. After the reaction, the reaction solvent was dried and the target product 5d (31 mg) was obtained by column chromatography (the eluent was preferably petroleum ether: ethyl acetate = 15:1 to 10:1), with a yield of 72%. The product 5d was analyzed, and the results were as follows: 1H NMR (400MHz, CDCl3): δ7.85(s,1H),7.68-7.65(m,2H),7.44(d,J=7.8Hz,2H),7.36-7.29(m,4H),7.24(s,1H),7.15(t,J=7.6Hz,1H),7.04 (t,J=7.2Hz,1H),6.81-6.77(m,2H),5.82(dd,J=9.6,3.2Hz,1H),3.79(dd,J=16.5,9.6Hz,1H),3.33(dd,J=16.5,3.2Hz,1H),2.60(s,3H); 13 C NMR (101MHz, CDCl3): δ195.7,194.3,148.6,140.0,139.8,134.8,134.5,129.9,129.4,129.2,129.1,128.8,128.7,122 .3,120.9,118.4,117.5,64.8,40.7,23.9;IR(neat):ν3826,3542,3021,2871,2633,1528,1441,1153,1022,733,654cm –1 ; HRMS (ESI): m / z [MH] - calcd.forC 24 H 19 N3O2Cl:416.1171; found:416.1167.

[0110] Embodiment 23:

[0111]

[0112] 2-aminochalcone 4e (30.2 mg, 0.10 mmol), α-halohydrazone 2a (39 mg, 0.20 mmol) and acetonitrile (1.0 ml) were added to the reaction flask in sequence, and finally triethylamine (20.2 mg, 0.20 mmol) was added, and the mixture was reacted at 60°C for 4 hours. After the reaction, the reaction solvent was dried and the target product 5e (23 mg) was obtained by column chromatography (the eluent is preferably petroleum ether: ethyl acetate = 15:1 to 10:1), with a yield of 50%. The product 5e was analyzed, and the results are as follows: 1H NMR (400MHz, CDCl3): δ7.91-7.90 (m, 2H), 7.71 (d, J = 7.8Hz, 1H), 7.67 (d, J = 8. 8Hz,1H),7.49(d,J=7.8Hz,2H),7.42-7.38(m,2H),7.32-7.28(m,2H),7.22(t, J=9.0Hz,1H),7.10(t,J=7.2Hz,1H),6.87-6.84(m,2H),5.87(dd,J=9.5,3.3Hz ,1H),3.83(dd,J=16.6,9.5Hz,1H),3.40(dd,J=16.6,3.3Hz,1H),2.67(s,3H); 13 C NMR (101MHz, CDCl3): δ195.6,194.3,148.6,140.0,138.2,136.1,134.5,131.0,130.1,129.9,129.24,129.15,128.6,126.5,1 22.9,122.4,120.9,118.5,117.5,64.8,40.8,24.0;IR(neat):ν3897,3651,3322,2941,2703,1506,1387,1153,992,733,641cm –1 ; HRMS (ESI): m / z [MH] - calcd.for C 24 H 19 N3O2Br:460.0666; found:460.0662.

[0113] Embodiment 24:

[0114]

[0115] 2-aminochalcone 4f (25.3 mg, 0.10 mmol), α-halohydrazone 2a (78 mg, 0.40 mmol) and acetonitrile (1.0 ml) were added to the reaction flask in sequence, and finally triethylamine (20.2 mg, 0.20 mmol) was added, and the mixture was reacted at 25°C for 8 hours. After the reaction, the reaction solvent was dried and the target product 5f (38 mg) was obtained by column chromatography (the eluent was preferably petroleum ether: ethyl acetate = 15:1 to 10:1), with a yield of 93%. The product 5f was analyzed, and the results were as follows: 1H NMR (400MHz, CDCl3): δ7.82(s,1H),7.44-7.33(m,6H),7.19(d,J=7.5Hz,1H),7.17(t,J=7.8Hz,1H),7.04(t,J=7.2Hz,1H),6.91(t,J=8.1Hz ,1H),6.86-6.77(m,3H),5.79(dd,J=9.6,3.9Hz,1H),3.79(dd,J=16.4,9.6Hz,1H),3.66(s,3H),3.49(dd,J=16.4,3.9Hz,1H),2.58(s,3H); 13 C NMR (101MHz, CDCl3): δ198.9,194.3,158.3,149.0,139.9,134.8,133.6,130.3,129.7,129.1,129.0,128.8,127.7,122.0,120.6 ,120.6,118.2,117.5,111.3,65.3,55.2,45.4,23.9;IR(neat):ν3664,3458,3213,2896,2658,1432,1189,1031,982,720,598cm –1 ; HRMS (ESI): m / z [MH] - calcd.for C 25 H 22 N3O3:412.1667; found:412.1660.

[0116] Embodiment 25:

[0117]

[0118] 2-aminochalcone 4g (28.3mg, 0.10mmol) and α-halogenated hydrazone 2a (19.5mg, 0.10mmol) and acetonitrile (1.0ml) were added to the reaction flask in sequence, and finally triethylamine (20.2mg, 0.20mmol) was added, and the mixture was reacted at 25°C for 8 hours. After the reaction, the reaction solvent was dried and the target product 5g (23mg) was obtained by column chromatography (the eluent was preferably petroleum ether: ethyl acetate = 15:1-10:1), with a yield of 52%. The product 5g was analyzed, and the results were as follows: 1H NMR (400MHz, CDCl3): δ7.85(s,1H),7.46(d,J=7.9Hz,2H),7.37-7.33(m,4H),7.27-7.25(m,1H),7.16(t,J=7.7Hz,1H),7.04(t,J=7.2Hz,1H),6. 82-6.75(m,3H),5.86(dd,J=9.6,3.3Hz,1H),3.90(s,3H),3.85(s,3H),3.80(dd,J=16.2,9.6Hz,1H),3.35(dd,J=16.2,3.4Hz,1H),2.61(s,3H); 13 C NMR (101MHz, CDCl3): δ195.4,194.4,153.4,148.9,148.7,140.0,134.5,130.0,129.8,129.10,129.08,128.9,122.8,122.2,120.9,1 18.4,117.4,110.0,109.7,64.9,56.0,55.9,40.2,23.9;IR(neat):ν3876,3562,3031,2889,2743,1401,1321,1236,1102,821,639cm –1 ; HRMS (ESI): m / z [MH] - calcd.for C 26 H 25 N3O4:442.1770; found:442.1772.

[0119] Embodiment 26:

[0120]

[0121] 2-aminochalcone 4h (22.9 mg, 0.10 mmol), α-halohydrazone 2a (39 mg, 0.20 mmol), and acetonitrile (1.0 ml) were added to the reaction flask in sequence, and finally 1,8-diazabicycloundec-7-ene (30.4 mg, 0.20 mmol) was added, and the reaction was carried out at 25°C for 8 hours. After the reaction was completed, the reaction solvent was dried and the target product 5h (31 mg) was obtained by column chromatography (the eluent was preferably petroleum ether: ethyl acetate = 15:1 to 10:1), with a yield of 80%. The product 5h was analyzed, and the results were as follows: 1HNMR (400MHz, CDCl3): δ7.87(s,1H),7.57(d,J=5.9Hz,1H),7.51(d,J=4.8Hz ,1H),7.46(d,J=7.8Hz,2H),7.38-7.34(m,2H),7.24(d,J=7.6Hz,1H),7.15(t ,J=7.4Hz,1H),7.05-7.00(m,2H),6.81-6.78(m,2H),5.81(dd,J=9.7,3.5Hz, 1H), 3.74 (dd, J=15.8, 9.8Hz, 1H), 3.34 (dd, J=15.8, 3.5Hz, 1H), 2.61 (s, 3H); 13 C NMR (101MHz, CDCl3): δ194.3,189.5,148.7,143.8,140.0,134.5,134.2,132.2,129.9,129.2,129.1,128.5,128.0,122 .4,120.9,118.4,117.5,65.0,41.3,23.9;IR(neat):ν3902,3655,3329,2887,2537,1608,1572,1323,1107,787,627cm –1 ; HRMS (ESI): m / z [MH] - calcd.for C 22 H 18 N3O2S:388.1125; found:388.1119.

[0122] Embodiment 27:

[0123]

[0124] 2-aminochalcone 4i (20.3 mg, 0.10 mmol), α-halohydrazone 2a (39 mg, 0.20 mmol), and acetonitrile (1.0 ml) were added to the reaction flask in sequence, and finally diisopropylethylamine (25.9 mg, 0.20 mmol) was added, and the mixture was reacted at 25°C for 12 hours. After the reaction, the reaction solvent was dried and the target product 5i (34.5 mg) was obtained by column chromatography (the eluent is preferably petroleum ether: ethyl acetate = 15:1 to 10:1), with a yield of 95%. The product 5i was analyzed, and the results are as follows: 1H NMR (400MHz, CDCl3): δ7.83(s,1H),7.45(d,J=7.8Hz,2H),7.38-7.33(m,2H),7.18-7.14(m,2H),7.04(t,J=7.2Hz,1H),6.82(t,J =7.2Hz,2H),5.72(dd,J=10.2,3.2Hz,1H),3.47(dd,J=16.1,10.2Hz,1H),2.72(dd,J=16.1,2.8Hz,1H),2.59(s,3H),0.85(s,9H); 13 C NMR (101MHz, CDCl3): δ212.3,194.3,148.6,140.1,134.0,130.0,129.1(2C),128.3,122.1,120.7,118.1,11 7.3,64.6,44.3,38.6,25.2,23.9;IR(neat):ν3122,3017,2787,2053,2142,1326,1172,1053,907,756,534cm –1 ; HRMS (ESI): m / z [MH] - calcd.for C 22 H 24 N3O2:362.1871; found:362.1874.

[0125] Embodiment 28:

[0126]

[0127] 2-aminochalcone 4j (26.7 mg, 0.10 mmol), α-halohydrazone 2a (39 mg, 0.20 mmol) and acetonitrile (1.0 ml) were added to the reaction flask in sequence, and finally cesium carbonate (65 mg, 0.20 mmol) was added, and the mixture was reacted at 25°C for 8 hours. After the reaction, the reaction solvent was dried and the target product 5j (11 mg) was obtained by column chromatography (the eluent is preferably petroleum ether: ethyl acetate = 15:1 to 10:1), with a yield of 25%. The product 5j was analyzed, and the results are as follows: 1H NMR (400MHz, CDCl3): δ7.86 (s, 1H), 7.46 (d, J = 7.8Hz, 2H), 7.38-7.33 (m, 3H), 7.2 8(d,J=7.6Hz,1H),7.25(d,J=1.6Hz,1H),7.16(t,J=7.7Hz,1H),7.04(t,J=7.2Hz, 1H),6.82(t,J=7.6Hz,2H),6.74(d,J=8.2Hz,1H),5.98(s,2H),5.86(dd,J=9.6,3. 2Hz,1H),3.77(dd,J=16.4,9.7Hz,1H),3.29(dd,J=16.4,3.2Hz,1H),2.62(s,3H); 13 C NMR (101MHz, CDCl3): δ194.8,194.3,151.9,148.7,148.1,140.0,134.4,131.4,130.0,129.1(2C),129.0,128.8,124.4,122.2, 120.8,118.4,117.4,107.7,101.8,64.8,40.5,23.9;IR(neat):ν3911,3742,3085,2879,2803,1392,1266,1195,983,826,638cm –1 ; HRMS (ESI): m / z [MH] - calcd.for C 25 H 20 N3O4:426.1459; found:426.1453.

[0128] Embodiment 29:

[0129]

[0130] 2-aminochalcone 4k (28.7 mg, 0.10 mmol), α-halohydrazone 2a (39 mg, 0.20 mmol) and acetonitrile (1.0 ml) were added to the reaction flask in sequence, and potassium tert-butoxide (22.4 mg, 0.20 mmol) was added at last, and the mixture was reacted at 25°C for 8 hours. After the reaction, the reaction solvent was dried and the target product 5k (13 mg) was obtained by column chromatography (the eluent was preferably petroleum ether: ethyl acetate = 15:1 to 10:1), with a yield of 28%. The product 5k was analyzed, and the results were as follows: 1H NMR (400MHz, CDCl3): δ7.86 (s, 1H), 7.46 (d, J = 7.8Hz, 2H), 7.38-7.33 (m, 3H), 7.2 8(d,J=7.6Hz,1H),7.25(d,J=1.6Hz,1H),7.16(t,J=7.7Hz,1H),7.04(t,J=7.2Hz, 1H),6.82(t,J=7.6Hz,2H),6.74(d,J=8.2Hz,1H),5.98(s,2H),5.86(dd,J=9.6,3. 2Hz,1H),3.77(dd,J=16.4,9.7Hz,1H),3.29(dd,J=16.4,3.2Hz,1H),2.62(s,3H); 13 C NMR (101MHz, CDCl3): δ194.8,194.3,151.9,148.7,148.1,140.0,134.4,131.4,130.0,129.1(2C),129.0,128.8,124.4,122.2, 120.8,118.4,117.4,107.7,101.8,64.8,40.5,23.9;IR(neat):ν3911,3742,3085,2879,2803,1392,1266,1195,983,826,638cm –1 ; HRMS (ESI): m / z [MH] - calcd.for calcd.forC 25 H 20 N3O4:426.1459; found:426.1453.

[0131] Embodiment 30:

[0132]

[0133] 2-aminochalcone 4a (22.3 mg, 0.10 mmol), α-halohydrazone 2b (42 mg, 0.20 mmol) and acetonitrile (1.0 ml) were added to the reaction flask in sequence, and finally triethylamine (20.2 mg, 0.20 mmol) was added, and the mixture was reacted at 25°C for 8 hours. After the reaction, the reaction solvent was dried and the target product 5l (44 mg) was obtained by column chromatography (the eluent was preferably petroleum ether: ethyl acetate = 15:1 to 10:1), with a yield of 95%. The product 5l was analyzed, and the results were as follows: 1H NMR (400MHz, CDCl3): δ7.86 (s, 1H), 7.68 (d, J = 8.2Hz, 2H), 7.47 (d, J = 8.0Hz ,2H),7.38(t,J=7.4Hz,2H),7.31(d,J=7.5Hz,1H),7.17-7.12(m,3H),7.05 (t,J=7.2Hz,1H),6.83-6.78(m,2H),5.90(dd,J=9.6,3.0Hz,1H),3.84(dd, J=16.6,9.7Hz,1H),3.36(dd,J=16.6,3.1Hz,1H),2.62(s,3H),2.36(s,3H); 13 C NMR (101MHz, CDCl3): δ196.3,194.3,148.7,144.1,140.0,134.5,134.0,130.0,129.1,129.1,129.0,128.9,128.1, 122.2,120.8,118.4,117.4,64.6,40.7,23.9,21.6;IR(neat):ν3891,3742,3008,2752,1657,1457,1270,757,691cm –1 ; HRMS (ESI): m / z [MH] - calcd.for C 25 H 22 N3O2:396.1714; found:396.1718.

[0134] Embodiment 31:

[0135]

[0136] 2-aminochalcone 4a (22.3 mg, 0.10 mmol), α-halohydrazone 2b (42 mg, 0.20 mmol) and acetonitrile (1.0 ml) were added to the reaction flask in sequence, and finally triethylamine (20.2 mg, 0.20 mmol) was added, and the mixture was reacted at 25°C for 8 hours. After the reaction, the reaction solvent was dried and the target product 5m (44 mg) was obtained by column chromatography (the eluent was preferably petroleum ether: ethyl acetate = 15:1 to 10:1), with a yield of 95%. The product 5m was analyzed, and the results were as follows: 1H NMR (400MHz, CDCl3): δ7.86 (s, 1H), 7.68 (d, J = 8.2Hz, 2H), 7.47 (d, J = 8.0Hz ,2H),7.38(t,J=7.4Hz,2H),7.31(d,J=7.5Hz,1H),7.17-7.12(m,3H),7.05 (t,J=7.2Hz,1H),6.83-6.78(m,2H),5.90(dd,J=9.6,3.0Hz,1H),3.84(dd, J=16.6,9.7Hz,1H),3.36(dd,J=16.6,3.1Hz,1H),2.62(s,3H),2.36(s,3H); 13 C NMR (101MHz, CDCl3): δ196.3,194.3,148.7,144.1,140.0,134.5,134.0,130.0,129.1,129.1,129.0,128.9,128.1, 122.2,120.8,118.4,117.4,64.6,40.7,23.9,21.6;IR(neat):ν3891,3742,3008,2752,1657,1457,1270,757,691cm –1 ; HRMS (ESI): m / z [MH] - calcd.for C 25 H 22 N3O2:396.1714; found:396.1718.

[0137] Embodiment 32:

[0138]

[0139] 2-aminochalcone 4a (22.3 mg, 0.10 mmol), α-halohydrazone 2d (44 mg, 0.20 mmol) and acetonitrile (1.0 ml) were added to the reaction flask in sequence, and finally triethylamine (20.2 mg, 0.20 mmol) was added, and the mixture was reacted at 25°C for 8 hours. After the reaction, the reaction solvent was dried and the target product 5n (35 mg) was obtained by column chromatography (the eluent was preferably petroleum ether: ethyl acetate = 15:1 to 10:1), with a yield of 85%. The product 5n was analyzed, and the results were as follows: 1H NMR (400MHz, CDCl3): δ7.96 (s, 1H), 7.80 (d, J = 7.2Hz, 2H), 7.60-7.56 (m, 2H), 7.55(t,J=7.4Hz,1H),7.46-7.38(m,4H),7.34(d,J=6.5Hz,1H),7.21(t,J=7. 8Hz,1H),6.90(t,J=7.5Hz,1H),6.85(d,J=7.9Hz,1H),6.03(dd,J=7.9,4.7Hz ,1H),3.70(dd,J=17.1,8.0Hz,1H),3.52(dd,J=17.1,4.7Hz,1H),2.60(s,3H); 13 C NMR (101MHz, CDCl3): δ196.2,194.2,150.8,139.4,136.5,136.2,133.6,133.3,129.4,128.7,128.6,128.0(2C),121. 8,119.6,118.8,115.4,103.1,62.2,41.2,24.1;IR(neat):ν3451,3128,2876,2695,2150,1637,1372,1028,877,594cm –1 ; HRMS (ESI): m / z [MH] - calcd.for C 25 H 19 N4O2:407.1512; found:407.1514.

[0140] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for synthesizing an indoline and benzotriazepine compound, characterized in that: The method comprises the following steps: using α-halohydrazone and 2-aminochalcone as reactants, adding a cyclizing base, reacting in an organic solvent at 0-60° C. for 2-24 hours, and obtaining an indoline compound represented by formula (I) or a benzotriazepine compound represented by formula (II): The ring-closing base is selected from one or more of triethylamine, diisopropylethylamine, 1,8-diazabicycloundec-7-ene, cesium carbonate, potassium tert-butoxide, and sodium bicarbonate.

2. The method for synthesizing indoline and benzotriazepine compounds according to claim 1, characterized in that: The organic solvent is one or more of dichloromethane, chloroform, 1,2-dichloroethane and acetonitrile.

3. The method for synthesizing indoline and benzotriazepine compounds according to claim 1, characterized in that: In terms of molar amount, the amount of the cyclizing base is 1-4 times that of 2-aminochalcone; and the amount of the α-halogenated hydrazone is 2 times that of 2-aminochalcone.

4. The method for synthesizing indoline and benzotriazepine compounds according to claim 1, characterized in that: When the product is a compound of formula (I), the chemical structural formula of the 2-aminochalcone is Where R 1 is selected from one of hydrogen, 5-methyl, 5-methoxy, 5-fluoro, 5-chloro, 5-bromo, 4-chloro, 4-bromo or 3-fluoro; R 2 is selected from phenyl, 4-methylphenyl, 4-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 3-methylphenyl, 3-methoxyphenyl, 3-bromophenyl, 2-methylphenyl, 2-chlorophenyl, 2-furyl, 3-thienyl, 2-naphthyl, methyl, ethyl, n-butyl, cyclopropyl, methoxy or one of the compounds of formula (III), R 3 One selected from 4-methylphenylsulfonyl, 4-fluorophenylsulfonyl, 4-chlorophenylsulfonyl, 4-bromophenylsulfonyl, 4-nitrophenylsulfonyl, 4-trifluoromethylphenylsulfonyl, phenylsulfonyl, 2-naphthylsulfonyl, 2-thienylsulfonyl or cyclopropylsulfonyl.

5. The method for synthesizing indoline and benzotriazepine compounds as claimed in claim 1, characterized in that: When the product is a compound of formula (I), the chemical structural formula of the α-halogenated hydrazone is Where R 4 It is selected from the group consisting of phenyl, 4-chlorophenyl, 4-bromophenyl, 4-methylphenyl, 4-methoxyphenyl, 3-chlorophenyl and 1-naphthyl.

6. The method for synthesizing indoline and benzotriazepine compounds according to claim 1, characterized in that: When the product is a compound of formula (II), the chemical structural formula of the 2-aminochalcone is Where R 1 is selected from the group consisting of hydrogen, 5-methoxy, 5-fluoro, 5-chloro, 4-methoxy, and 4-chloro; R 2 is selected from phenyl, 4-methylphenyl, 4-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-trifluoromethylphenyl, 4-biphenyl, 3-chlorophenyl, 3-bromophenyl, 3-methoxyphenyl, 2-methoxyphenyl, 2-chlorophenyl, 3,4-dimethoxyphenyl, 2,4-dichlorophenyl, 1-naphthyl, 2-naphthyl, 2-furyl, 2-thienyl, methyl, tert-butyl, cyclopropyl, methoxy or one of the compounds of formula (IV): R 3 For hydrogen.

7. The method for synthesizing indoline and benzotriazepine compounds according to claim 1, characterized in that: When the product is a compound of formula (II), the chemical structural formula of the α-halogenated hydrazone is Where R 4 It is selected from the group consisting of phenyl, 4-chlorophenyl, 4-bromophenyl, 4-methylphenyl, 4-methoxyphenyl, 4-cyanophenyl, 4-nitrophenyl, 3-chlorophenyl, 2-fluorophenyl and 1-naphthyl.

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