An imidazo[1,2-a]pyrimidine matrine / sophoridine derivative, a preparation method and application thereof

Abstract

The application provides an imidazo[1,2-a]pyrimidine matrine / sophoridine derivative, which has the chemical structural formula as shown in the description. 1 R is alpha-hydrogen or beta-hydrogen; and R 2 is selected from phenyl, substituted phenyl and naphthyl. Compared with the parent matrine and sophoridine, the acaricidal activity of the imidazo[1,2-a]pyrimidine matrine / sophoridine derivative is significantly improved, and the imidazo[1,2-a]pyrimidine matrine / sophoridine derivative can be used for preparing a plant source acaricide which is high in efficiency, environmental protection and low in toxicity.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of organic synthesis and relates to a matrine / sophoridine derivative, in particular to an imidazo[1,2-a]pyrimidine matrine / sophoridine derivative, a preparation method and application thereof. BACKGROUND

[0002] Matrine and sophoridine are quinolinoridine alkaloids extracted from Sophora plants. The structure mainly consists of four rings A, B, C and D, and four chiral centers. Matrine has wide biological activities. In the medical field, it has multiple activities such as anticancer, immunosuppression, anti-fibrosis, neuroprotection and antiviral activity; in the agricultural aspect, it has insecticidal activity. Sophoridine not only has good solubility and biological safety, but also has wide biological activities such as antiviral, anticancer, anti-inflammatory and insecticidal activity. Imidazo[1,2-a]pyrimidine is a kind of aromatic heterocyclic compound, which has diverse biological activities and is widely used in the fields of pesticides and medicines. At present, there is no report on introducing imidazo[1,2-a]pyrimidine into the chemical structure of matrine and sophoridine to improve the insecticidal activity. SUMMARY

[0003] In view of the deficiencies in the prior art, the purpose of the present application is to provide an imidazo[1,2-a]pyrimidine matrine / sophoridine derivative, a preparation method and application thereof, which solves the technical problem that the acaricidal activity of matrine / sophoridine in the prior art needs to be further improved.

[0004] In order to solve the above technical problems, the present application adopts the following technical solutions:

[0005] An imidazo[1,2-a]pyrimidine matrine / sophoridine derivative, the chemical structural formula of which is shown as formula IV:

[0006]

[0007] In the formula, R

[0008] R 1 is alpha-hydrogen or beta-hydrogen; R 1 When R 1 is beta-hydrogen, formula IV represents an imidazo[1,2-a]pyrimidine sophoridine derivative; R 2 is selected from phenyl, substituted phenyl and naphthyl.

[0009] The present application also has the following technical features:

[0010] Preferably and specifically, R 2selected from the group consisting of phenyl, o-methylphenyl, m-methylphenyl, p-methylphenyl, o-methoxyphenyl, m-methoxyphenyl, p-methoxyphenyl, p-phenoxyphenyl, o-fluorophenyl, m-fluorophenyl, p-fluorophenyl, o-chlorophenyl, m-chlorophenyl, p-chlorophenyl, o-bromophenyl, m-bromophenyl, p-bromophenyl, o-trifluoromethylphenyl, m-trifluoromethylphenyl, p-trifluoromethylphenyl, o-nitrophenyl, m-nitrophenyl, p-nitrophenyl, 2,5-difluorophenyl, 3,4-dichlorophenyl, p-trifluoromethoxyphenyl, 1-naphthyl, 2-naphthyl.

[0011] The present application also protects a method for preparing the imidazo[1,2-a]pyrimidine matrine / sophoridine derivative as described above, which comprises: first, using matrine and phosphorus oxychloride as reactants, or using sophoridine and phosphorus oxychloride as reactants, to prepare intermediate II-1 or II-2; then using intermediate II-1 and guanidine hydrochloride as reactants, or using intermediate II-2 and guanidine hydrochloride as reactants, to prepare intermediate III-1 or III-2; finally, using intermediate III-1 and an α-bromo aromatic ketone as reactants, or using intermediate III-2 and an α-bromo aromatic ketone as reactants, to prepare the imidazo[1,2-a]pyrimidine matrine or sophoridine derivative;

[0012] The chemical structural formula of matrine and sophoridine is shown in formula I-1 and formula I-2 respectively:

[0013]

[0014] The chemical structural formula of intermediate II-1 or II-2 is shown in formula II-1 or II-2 respectively:

[0015]

[0016] The chemical structural formula of intermediate III-1 or III-2 is shown in formula III-1 or III-2 respectively:

[0017]

[0018] Preferably and particularly, the α-bromo aromatic ketone is selected from the group consisting of α-bromoacetophenone, o-methyl-α-bromoacetophenone, m-methyl-α-bromoacetophenone, p-methyl-α-bromoacetophenone, o-methoxy-α-bromoacetophenone, m-methoxy-α-bromoacetophenone, p-methoxy-α-bromoacetophenone, p-phenoxy-α-bromoacetophenone, o-fluoro-α-bromoacetophenone, m-fluoro-α-bromoacetophenone, p-fluoro-α-bromoacetophenone, o-chloro-α-bromoacetophenone, m-chloro-α-bromoacetophenone, p-chloro-α-bromoacetophenone, o-bromo-α-bromoacetophenone, m-bromo-α-bromoacetophenone, p-bromo-α-bromoacetophenone, o-trifluoromethyl-α-bromoacetophenone, m-trifluoromethyl-α-bromoacetophenone, p-trifluoromethyl-α-bromoacetophenone, o-nitro-α-bromoacetophenone, m-nitro-α-bromoacetophenone, p-nitro-α-bromoacetophenone, 2,5-difluoro-α-bromoacetophenone, 3,4-dichloro-α-bromoacetophenone, p-trifluoromethoxy-α-bromoacetophenone, α-bromo-1-naphthylacetophenone, α-bromo-2-naphthylacetophenone.

[0019] In particular, the method comprises the following steps:

[0020] Step one: slowly drop phosphorus oxychloride into solvent at -5-5°C, then drop the solution containing matrine or sophoridine into the above system, gradually heat to 15-35°C, react for 4-6h, then remove the solvent in the system under reduced pressure, add ice water and adjust the pH value of the system, then heat to 50-70°C and stir for 1-7h, filter the product, wash the filter cake and purify by column chromatography to obtain intermediate II-1 or II-2.

[0021] Step two: add potassium carbonate and guanidine hydrochloride into the solution containing intermediate II-1 or II-2, heat to reflux for 8-14h, then cool to 15-35°C, remove the solvent under reduced pressure, then extract, combine the organic phase, dry, concentrate and purify by column chromatography to obtain intermediate III-1 or III-2.

[0022] Step three: slowly add α-bromo aromatic ketone into the solution containing intermediate III-1 or III-2, stir at 15-35°C for 5-17h, then add NaCl solution into the reaction system, extract, combine the organic phase, dry, concentrate and purify by thin layer chromatography to obtain imidazo[1,2-a]pyrimidine matrine or sophoridine derivative.

[0023] Preferably and particularly, in step one, the solvent consists of N,N-dimethylformamide and dichloromethane, and the volume ratio of N,N-dimethylformamide to dichloromethane is 3:25.

[0024] Preferably and specifically, in step one, the solution containing matrine or sophoridine is prepared by using dichloromethane as a solvent.

[0025] Preferably and specifically, in step one, the pH value of the system is adjusted to 8-9 by using 40wt% NaOH solution.

[0026] Preferably and specifically, in step one, the molar ratio of the phosphorus oxychloride to matrine is 10:1; the molar ratio of the phosphorus oxychloride to sophoridine is 10:1.

[0027] Preferably and specifically, in step two, the solution containing the intermediate II-1 or II-2 is prepared by using n-butanol as a solvent.

[0028] Preferably and specifically, in step two, the molar ratio of the potassium carbonate, guanidine hydrochloride and the intermediate II-1 is 3:1.5:1; the molar ratio of the potassium carbonate, guanidine hydrochloride and the intermediate II-2 is 3:1.5:1.

[0029] Preferably and specifically, in step three, the solution containing the intermediate III-1 or III-2 is prepared by using N,N-dimethylformamide as a solvent.

[0030] Preferably and specifically, in step three, the molar ratio of the intermediate III-1 and the α-bromo aromatic ketone is 1:1.2; the molar ratio of the intermediate III-2 and the α-bromo aromatic ketone is 1:1.2.

[0031] The application also protects the use of the imidazo[1,2-a]pyrimidine matrine / sophoridine derivative as described above for preparing acaricides; the use includes: using Tetranychus cinnabarinus female adults as test mites, and using 500mg / L of the imidazo[1,2-a]pyrimidine matrine / sophoridine derivative solution as the primary screening solution.

[0032] Compared with the prior art, the application has the following technical effects:

[0033] (I) Compared with the parent matrine and sophoridine, the acaricidal activity of the imidazo[1,2-a]pyrimidine matrine / sophoridine derivative of the application is significantly improved, and the derivative can be used for preparing plant source acaricides with high efficiency, environmental protection and low toxicity.

[0034] (II) The application first proposes the technical idea of introducing imidazo[1,2-a]pyrimidine into the chemical structure of matrine and sophoridine, and the synthesis method has simple steps and does not need the participation of a catalyst in the synthesis process. BRIEF DESCRIPTION OF DRAWINGS

[0035] Figure 1 The nuclear magnetic resonance hydrogen spectrum of the compound IV-6.

[0036] Figure 2The NMR spectrum of compound IV-11.

[0037] Figure 3 The NMR spectrum of compound IV-35.

[0038] Figure 4 The NMR spectrum of compound IV-42.

[0039] The specific content of the present application is further explained in detail in the following combined with examples. DETAILED DESCRIPTION

[0040] The synthetic route of the present application is as follows:

[0041]

[0042] Compound I-1 is matrine (CAS code: 519-02-8), and compound I-2 is sophoridine (CAS code: 6882-68-4), both of which are epimers. Compound II-1 and compound III-1 are intermediates of examples 1 to 28, and compounds IV-1 to IV-28 are target products of examples 1 to 28. Compound II-2 and compound III-2 are intermediates of examples 29 to 56, and compounds IV-29 to IV-56 are target products of examples 29 to 56.

[0043] R 2 Ph, 2-CH3Ph, 3-CH3Ph, 4-CH3Ph, 2-OCH3Ph, 3-OCH3Ph, 4-OCH3Ph, 4-PhOPh, 2-FPh, 3-FPh, 4-FPh, 2-ClPh, 3-ClPh, 4-ClPh, 2-BrPh, 3-BrPh, 4-BrPh, 2-CF3Ph, 3-CF3Ph, 4-CF3Ph, 2-NO2Ph, 3-NO2Ph, 4-NO2Ph, 2,5-di-FPh, 3,4-di-ClPh, 4-OCF3Ph, 1-naphthalene, 2-naphthalene.

[0044] It should be noted that all the raw materials used in the present application are conventional raw materials known in the art, unless otherwise specified.

[0045] The following gives specific examples of the present application, it should be noted that the present application is not limited to the following specific examples, any equivalent transformation made on the basis of the technical solutions of the present application falls within the protection scope of the present application.

[0046] Example 1:

[0047] The embodiment provides a preparation method of an imidazo[1,2-a]pyrimidine matrine derivative, and the method specifically comprises the following steps:

[0048] Step one: 15 mmol of phosphorus oxychloride (CAS code: 10025-87-3) is slowly added into a mixed solvent of N,N-dimethylformamide (DMF) and dichloromethane (the volume ratio of N,N-dimethylformamide and dichloromethane is 3:25) under the condition of ice bath at 0 DEG C, then 1.5 mmol of matrine is added into dichloromethane to form a solution, and the solution is added into the above system; then the system is gradually warmed to room temperature and reacts for 5 h, dichloromethane in the system is removed by concentration under reduced pressure, ice water is added into the system, and the pH value is adjusted to 8-9 by using a 40 wt% NaOH solution; then the system is warmed to 60 DEG C and stirred for 2 h until a large amount of solid is precipitated, the solid is filtered, the filter cake is washed with ice water, and the obtained solid product is separated and purified by silica gel column chromatography, and the obtained solid product is intermediate II-1.

[0049] In the embodiment, the product prepared in step one is subjected to physical and chemical property and characterization analysis, and the results are as follows:

[0050] Physical and chemical property: yellow solid, the melting point is 105-106 DEG C, and the yield is 90%.

[0051] Infrared spectrum: IR cm -1 (KBr): 3467, 3047, 2944, 1639, 873, 611.

[0052] Nuclear magnetic resonance hydrogen spectrum: 1 H NMR (400 MHz, CDCl3) δ: 9.67 (s, 1H), 4.01-4.11 (m, 2H), 3.65 (t, J=12.8 Hz, 1H), 2.78-2.86 (m, 2H), 2.38-2.44 (m, 1H), 2.26-2.34 (m, 1H), 2.18 (s, 1H), 1.95-2.03 (m, 2H), 1.77-1.92 (m, 4H), 1.54-1.71 (m, 5H), 1.31-1.51 (m, 3H).

[0053] Step two: 3 mmol of potassium carbonate and 1.5 mmol of guanidine hydrochloride (CAS code: 50-01-1) are added into a n-butanol solution containing 1.0 mmol of intermediate II-1, heated to reflux for 10 h, cooled to room temperature, the solvent is removed by concentration under reduced pressure, water is added into the residue, extracted with ethyl acetate (20 mL x 3), the organic phases are combined, dried over anhydrous Na2SO4, concentrated, separated and purified by silica gel column chromatography, and the obtained solid product is intermediate III-1.

[0054] In the embodiment, the product prepared in step two is subjected to physical and chemical property and characterization analysis, and the results are as follows:

[0055] Physical and chemical properties: yellow solid, melting point 130-132 °C, yield 82%.

[0056] Infrared spectrum: IR cm -1 (KBr): 3355, 3163, 2925, 1651, 1603, 1545, 1462, 1332.

[0057] Nuclear magnetic resonance hydrogen spectrum: 1 H NMR (400 MHz, CDCI3) δ: 7.51 (s, 1H), 4.49-4.54 (m, 3H), 3.86-3.91 (m, 1H), 3.27 (t, J = 12.4 Hz, 1H), 2.79-2.87 (m, 2H), 2.40-2.53 (m, 2H), 2.13-2.14 (m, 1H), 1.89-2.05 (m, 4H), 1.61-1.83 (m, 5H), 1.51-1.60 (m, 2H), 1.33-1.49 (m, 3H).

[0058] Step three: 1 mmol of intermediate III-1 was dissolved in DMF, 1.2 mmol of α-bromo aromatic ketone was slowly added, stirred at room temperature for 5-17 h, after thin layer tracking detection reaction was completed, NaCl solution was added to the reaction system, then extracted with ethyl acetate (20 mL x 3), the organic phase was combined, dried over anhydrous Na2SO4, concentrated, and then the target compound IV-1 was obtained after separation and purification by thin layer chromatography.

[0059] In this embodiment, the α-bromo aromatic ketone is α-bromoacetophenone.

[0060] In this embodiment, the target compound IV-1 prepared in step three was subjected to physical and chemical property and characterization analysis, and the results were as follows:

[0061] Physical and chemical properties: yellow solid, melting point 130-132 °C, yield 52%.

[0062] Infrared spectrum: IR cm -1 (KBr): 3733, 2926, 2357, 1652, 1487, 1441, 1341, 704.

[0063] Nuclear magnetic resonance hydrogen spectrum: 1H NMR (400 MHz, CDC13) δ: 7.94 (d, J = 7.6 Hz, 2H), 7.63 (s, 1H), 7.33-7.38 (m, 3H), 7.22-7.24 (m, 1H), 4.91 (dd, J = 4.4 Hz, 13.2 Hz, 1H), 4.01-4.05 (m, 1H), 3.40 (t, J = 12.8 Hz, 1H), 2.86-2.94 (m, 2H), 2.55-2.68 (m, 2H), 2.12-2.23 (m, 2H), 2.00-2.08 (m, 2H), 1.69-1.92 (m, 6H), 1.38-1.58 (m, 5H).

[0064] The chemical structural formula is shown as formula IV-1:

[0065] Example 2:

[0066] This example gives a preparation method of imidazo[1,2-a]pyrimidine matrine derivative, which is basically the same as example 1, the difference is that in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is o-methyl-α-bromoacetophenone.

[0067] In this example, the target compound IV-2 prepared in step three is subjected to physical and chemical property and characterization analysis, and the results are as follows:

[0068] Physical and chemical properties: yellow solid, melting point 133-134℃, yield 46%.

[0069] Infrared spectrum: IR cm -1 (KBr): 3715, 2924, 2352, 1655, 1487, 1340, 721.

[0070] Nuclear magnetic resonance hydrogen spectrum: 1 H NMR (400 MHz, CDC13) δ: 7.94 (d, J = 7.6 Hz, 2H), 7.63 (s, 1H), 7.33-7.38 (m, 3H), 7.22-7.24 (m, 1H), 4.91 (dd, J = 4.4 Hz, 13.2 Hz, 1H), 4.01-4.05 (m, 1H), 3.40 (t, J = 12.8 Hz, 1H), 2.86-2.94 (m, 2H), 2.55-2.68 (m, 2H), 2.12-2.23 (m, 2H), 2.00-2.08 (m, 2H), 1.69-1.92 (m, 6H), 1.38-1.58 (m, 5H).

[0071] The chemical structural formula is shown as formula IV-2: The chemical structural formula is shown as formula IV-2:

[0072] Example 3

[0073] This example gives a preparation method of imidazo[1,2-a]pyrimidine matrine derivatives, which is basically the same as example 1, the difference is that: in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is m-methyl-α-bromoacetophenone.

[0074] In this example, the physical and chemical properties and characterization analysis of the target compound IV-3 prepared in step three were carried out, and the results were as follows:

[0075] Physical and chemical properties: yellow solid, melting point 132-134℃, yield 63%.

[0076] Infrared spectrum: IR cm -1 (KBr): 3687, 2927, 1654, 1487, 1342, 721.

[0077] Nuclear magnetic resonance hydrogen spectrum: 1 H NMR (400 MHz, CDCl3) δ: 7.83 (s, 1H), 7.70 (d, J = 8.0 Hz, 1H), 7.63 (s, 1H), 7.32 (s, 1H), 7.26-7.27 (m, 0.3H), 7.23-7.25 (m, 0.7H), 7.07 (d, J = 7.2 Hz, 1H), 4.91 (dd, J = 4.4 Hz, 12.8 Hz, 1H), 3.98-4.03 (m, 1H), 3.37 (t, J = 12.8 Hz, 1H), 2.81-2.89 (m, 2H), 2.53-2.69 (m, 2H), 2.38 (s, 3H), 2.12-2.20 (m, 2H), 1.98-2.04 (m, 2H), 1.70-1.88 (m, 6H), 1.37-1.57 (m, 5H).

[0078] The chemical structure is shown as formula IV-3:

[0079] Example 4

[0080] This example gives a preparation method of imidazo[1,2-a]pyrimidine matrine derivatives, which is basically the same as example 1, the difference is that: in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is p-methyl-α-bromoacetophenone.

[0081] In this example, the physical and chemical properties and characterization analysis of the target compound IV-3 prepared in step three were carried out, and the results were as follows:

[0082] Physical and chemical properties: yellow solid, melting point 139-141℃, yield 46%.

[0083] Infrared spectrum: IR cm -1 (KBr): 3696, 2926, 2353, 1653, 1484, 1341, 821.

[0084] Nuclear magnetic resonance hydrogen spectrum: 1 H NMR (400MHz, CDCI3) δ: 7.84 (d, J=8.4Hz, 2H), 7.62 (s, 1H), 7.29 (s, 1H), 7.19 (d, J=8.0Hz, 2H), 4.91 (dd, J=4.4Hz, 12.8Hz, 1H), 3.98-4.03 (m, 1H), 3.37 (t, J=12.8Hz, 1H), 2.82-2.90 (m, 2H), 2.54-2.68 (m, 2H), 2.35 (s, 3H), 2.12-2.19 (m, 2H), 1.96-2.04 (m, 2H), 1.68-1.92 (m, 6H), 1.38-1.57 (m, 5H).

[0085] The chemical structural formula is shown as formula IV-4:

[0086] Example 5:

[0087] This example gives a preparation method of imidazo[1, 2-a] pyrimidine matrine derivative, which is basically the same as example 1, the difference is that in step three, the α-brominated aromatic ketone is different. In this example, the α-brominated aromatic ketone is o-methoxy-α-bromoacetophenone.

[0088] In this example, the physical and chemical properties and characterization analysis of the target compound IV-5 prepared in step three are carried out, and the results are as follows:

[0089] Physical and chemical properties: yellow solid, melting point 145-146℃, yield 42%.

[0090] Infrared spectrum: IR cm -1 (KBr): 3689, 2926, 2359, 1653, 1488, 1340, 704.

[0091] Nuclear magnetic resonance hydrogen spectrum: 1H NMR (400 MHz, CDC13) δ: 8.50-8.52 (m, 1H), 7.69 (s, 1H), 7.64 (s, 1H), 7.21-7.25 (m, 1H), 7.07 (t, J = 7.2 Hz, 1H), 6.95 (d, J = 8.0 Hz, 1H), 4.93 (dd, J = 4.8 Hz, 13.2 Hz, 1H), 3.98-4.03 (m, 1H), 3.96 (s, 3H), 3.37 (t, J = 12.8 Hz, 1H), 2.82-2.90 (m, 2H), 2.55-2.69 (m, 2H), 2.12-2.20 (m, 2H), 1.96-2.04 (m, 2H), 1.68-1.92 (m, 6H), 1.37-1.58 (m, 5H).

[0092] The chemical structure is shown as formula IV-5.

[0093] Example 6

[0094] This example gives a preparation method of imidazo[1,2-a]pyrimidine matrine derivatives, which is basically the same as example 1, the difference is that in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is m-methoxy-α-bromoacetophenone.

[0095] In this example, the target compound IV-6 prepared in step three was subjected to physical and chemical property and characterization analysis, and the results were as follows:

[0096] Physical and chemical properties: yellow solid, melting point 131-132°C, yield 38%.

[0097] Infrared spectrum: IR cm -1 (KBr): 3740, 2927, 1654, 1486, 1343, 725.

[0098] Nuclear magnetic resonance hydrogen spectrum: 1H NMR (400 MHz, CDC13) δ: 7.63 (s, 1H), 7.60-7.61 (m, 1H), 7.45 (d, J = 8.0 Hz, 1H), 7.33 (s, 1H), 7.28 (s, 0.5H), 7.24 (s, 0.5H), 6.80-6.82 (m, 1H), 4.92 (dd, J = 4.4 Hz, 12.8 Hz, 1H), 3.99-4.04 (m, 1H), 3.86 (s, 3H), 3.38 (t, J = 12.4 Hz, 1H), 2.82-2.90 (m, 2H), 2.55-2.69 (m, 2H), 2.12-2.20 (m, 2H), 1.96-2.04 (m, 2H), 1.68-1.92 (m, 6H), 1.38-1.57 (m, 5H).

[0099] The chemical structure is shown as formula IV-6:

[0100] Example 7:

[0101] This example gives a preparation method of imidazo[1,2-a]pyrimidine matrine derivative, which is basically the same as example 1, the difference is that in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is p-methoxy-α-bromoacetophenone.

[0102] In this example, the target compound IV-7 prepared in step three was analyzed for physical and chemical properties and characterization, and the results are as follows:

[0103] Physical and chemical properties: yellow solid, melting point 123-125°C, yield 48%.

[0104] Infrared spectrum: IR cm -1 (KBr): 3706, 2928, 1654, 1484, 1344, 1241, 835.

[0105] Nuclear magnetic resonance hydrogen spectrum: 1 H NMR (400 MHz, CDC13) δ: 7.63 (s, 1H), 7.60-7.61 (m, 1H), 7.45 (d, J = 8.0 Hz, 1H), 7.33 (s, 1H), 7.28 (s, 0.5H), 7.24 (s, 0.5H), 6.80-6.82 (m, 1H), 4.92 (dd, J = 4.4 Hz, 12.8 Hz, 1H), 3.99-4.04 (m, 1H), 3.86 (s, 3H), 3.38 (t, J = 12.4 Hz, 1H), 2.82-2.90 (m, 2H), 2.55-2.69 (m, 2H), 2.12-2.20 (m, 2H), 1.96-2.04 (m, 2H), 1.68-1.92 (m, 6H), 1.38-1.57 (m, 5H).

[0106] The chemical structural formula is shown as formula IV-7:

[0107] Example 8:

[0108] This example gives a preparation method of imidazo[1,2-a]pyrimidine matrine derivative, which is basically the same as example 1, the difference is that in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is p-phenoxy-α-bromoacetophenone.

[0109] In this example, the target compound IV-8 prepared in step three was subjected to physical and chemical property and characterization analysis, and the results are as follows:

[0110] Physical and chemical properties: yellow solid, melting point 134-135℃, yield 40%.

[0111] Infrared spectrum: IR cm -1 (KBr): 3686, 2926, 1653, 1482, 1342, 1229, 748.

[0112] Nuclear magnetic resonance hydrogen spectrum: 1 H NMR (400 MHz, CDCI3) δ: 7.91 (d, J = 8.8 Hz, 2H), 7.64 (s, 1H), 7.31-7.35 (m, 2H), 7.28 (s, 1H), 7.07-7.11 (m, 1H), 7.00-7.05 (m, 4H), 4.91 (dd, J = 4.4 Hz, 12.8 Hz, 1H), 4.01-4.03 (m, 1H), 3.38 (t, J = 12.8 Hz, 1H), 2.84-2.91 (m, 2H), 2.56-2.69 (m, 2H), 2.13-2.19 (m, 2H), 1.69-2.05 (m, 8H), 1.38-1.59 (m, 5H).

[0113] The chemical structural formula is shown as formula IV-8:

[0114] Example 9:

[0115] This example gives a preparation method of imidazo[1,2-a]pyrimidine matrine derivative, which is basically the same as example 1, the difference is that in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is p-phenoxy-α-bromoacetophenone.

[0116] In this example, the target compound IV-9 prepared in step three was subjected to physical and chemical property and characterization analysis, and the results are as follows:

[0117] Physical and chemical properties: yellow solid, melting point 129-131℃, yield 42%.

[0118] Infrared spectrum: IR cm -1 (KBr): 3737, 2926, 2354, 1653, 1486, 1439, 1341, 751.

[0119] Nuclear magnetic resonance hydrogen spectrum: 1 H NMR (400MHz, CDCI3) δ: 8.42 (s, 1H), 7.66 (s, 1H), 7.54 (s, 1H), 7.20 (s, 2H), 7.06-7.09 (m, 1H), 4.90-4.92 (m, 1H), 4.04 (s, 1H), 3.40 (t, J = 12.0 Hz, 1H), 2.85-2.93 (m, 2H), 2.57-2.69 (m, 2H), 2.17-2.21 (m, 2H), 1.76-2.04 (m, 8H), 1.40-1.57 (m, 5H).

[0120] The chemical structural formula is shown as formula IV-9:

[0121] Example 10:

[0122] This example gives a preparation method of imidazo[1, 2-a] pyrimidine matrine derivative, which is basically the same as example 1, the difference is that in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is m-fluoro-α-bromoacetophenone.

[0123] In this example, the physical and chemical properties and characterization analysis of the target compound IV-10 prepared in step three are carried out, and the results are as follows:

[0124] Physical and chemical properties: yellow solid, melting point 128-129℃, yield 50%.

[0125] Infrared spectrum: IR cm -1 (KBr): 3733, 2926, 2355, 1655, 1488, 1443, 1342, 876.

[0126] Nuclear magnetic resonance hydrogen spectrum: 1H NMR (400 MHz, CDCI3) δ: 7.65-7.69 (m, 3H), 7.34 (s, 1H), 7.28-7.32 (m, 1H), 6.90-6.95 (m, 1H), 4.91 (dd, J = 4.0 Hz, 12.8 Hz, 1H), 4.04 (s, 1H), 3.33-3.39 (m, 1H), 2.84-2.92 (m, 2H), 2.56-2.70 (m, 2H), 2.13-2.20 (m, 2H), 1.98-2.06 (m, 2H), 1.71-1.93 (m, 6H), 1.39-1.58 (m, 5H).

[0127] The chemical structural formula is shown as formula IV-10:

[0128] Example 11:

[0129] This example gives a preparation method of imidazo[1,2-a]pyrimidine matrine derivative, which is basically the same as example 1, the difference is that in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is p-fluoro-α-bromoacetophenone.

[0130] In this example, the target compound IV-11 prepared in step three was subjected to physical and chemical property and characterization analysis, and the results are as follows:

[0131] Physical and chemical properties: yellow solid, melting point 158-159°C, yield 60%.

[0132] Infrared spectrum: IR cm -1 (KBr): 3717, 2929, 2353, 1656, 1552, 1485, 1343, 841.

[0133] Nuclear magnetic resonance hydrogen spectrum: 1 H NMR (400 MHz, CDCI3) δ: 7.65-7.69 (m, 3H), 7.34 (s, 1H), 7.28-7.32 (m, 1H), 6.90-6.95 (m, 1H), 4.91 (dd, J = 4.0 Hz, 12.8 Hz, 1H), 4.04 (s, 1H), 3.33-3.39 (m, 1H), 2.84-2.92 (m, 2H), 2.56-2.70 (m, 2H), 2.13-2.20 (m, 2H), 1.98-2.06 (m, 2H), 1.71-1.93 (m, 6H), 1.39-1.58 (m, 5H).

[0134] The chemical structural formula is shown as formula IV-11: The chemical structural formula is shown as formula IV-11:

[0135] Example 12

[0136] This example gives a preparation method of imidazo[1,2-a]pyrimidine matrine derivatives, which is basically the same as example 1, the difference is that: in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is o-chloro-α-bromoacetophenone.

[0137] In this example, the target compound IV-12 prepared in step three was subjected to physical and chemical property and characterization analysis, and the results were as follows:

[0138] Physical and chemical properties: yellow solid, melting point 201-202℃, yield 65%.

[0139] Infrared spectrum: IR cm -1 (KBr): 3727, 2925, 2353, 1654, 1486, 1342, 740.

[0140] Nuclear magnetic resonance hydrogen spectrum: 1 H NMR (400 MHz, CDCl3) δ: 8.48-8.50 (m, 1H), 7.85 (s, 1H), 7.67 (s, 1H), 7.40 (d, J = 8.0 Hz, 1H), 7.34 (t, J = 7.2 Hz, 1H), 7.15-7.18 (m, 1H), 4.92 (dd, J = 4.4 Hz, 12.8 Hz, 1H), 3.98-4.04 (m, 1H), 3.38 (t, J = 12.8 Hz, 1H), 2.81-2.89 (m, 2H), 2.56-2.70 (m, 2H), 2.13-2.20 (m, 2H), 1.70-2.04 (m, 8H), 1.39-1.58 (m, 5H).

[0141] The chemical structural formula is shown as formula IV-12:

[0142] Example 13

[0143] This example gives a preparation method of imidazo[1,2-a]pyrimidine matrine derivatives, which is basically the same as example 1, the difference is that: in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is m-chloro-α-bromoacetophenone.

[0144] In this example, the target compound IV-13 prepared in step three was subjected to physical and chemical property and characterization analysis, and the results were as follows:

[0145] Physical and chemical properties: yellow solid, melting point 230-232℃, yield 45%.

[0146] Infrared spectrum: IR cm -1 (KBr):3730,2926,2354,1654,1488,1342,748.

[0147] H NMR spectrum: 1 H NMR (400MHz, CDCl3) δ: 7.94-7.95 (m, 1H), 7.82 (d, J = 8.0Hz, 1H), 7.65 (s, 1H) ),7.34(s,1H),7.29-7.31(m,1H),7.19-7.21(m,1H),4.92(dd,J=4.4Hz,13 .2Hz,1H),4.05(s,1H),3.34-3.40(m,1H),2.88(s,2H),2.57-2.70(m,2H), 2.14-2.22(m,2H),2.02-2.06(m,2H),1.71-1.93(m,6H),1.40-1.59(m,5H).

[0148] Its chemical structure is shown in Formula IV-13:

[0149] Example 14:

[0150] This example provides a method for preparing an imidazo[1,2-a]pyrimidine matrine derivative, which is substantially the same as that of Example 1, except that in step 3, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is p-chloro-α-bromoacetophenone.

[0151] In this example, the target compound IV-14 obtained in step 3 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0152] Physical and chemical properties: yellow solid, melting point 177-179°C, yield 55%.

[0153] Infrared spectrum: IR cm -1 (KBr):3721,2926,2353,1653,1484,1341,832.

[0154] H NMR spectrum: 1H NMR (400 MHz, CDC13) δ: 7.87 (d, J = 8.4 Hz, 2H), 7.62 (s, 1H), 7.31-7.33 (m, 3H), 4.90 (dd, J = 4.0 Hz, 12.8 Hz, 1H), 4.03 (s, 1H), 3.33-3.39 (m, 1H), 2.84-2.92 (m, 2H), 2.56-2.68 (m, 2H), 2.14-2.20 (m, 2H), 1.98-2.06 (m, 2H), 1.70-1.93 (m, 6H), 1.39-1.58 (m, 5H).

[0155] The chemical structural formula is shown as formula IV-14:

[0156] Example 15:

[0157] This example gives a preparation method of imidazo[1,2-a]pyrimidine matrine derivative, which is basically the same as example 1, the difference is that in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is o-bromo-α-bromoacetophenone.

[0158] In this example, the target compound IV-15 prepared in step three was subjected to physical and chemical property and characterization analysis, and the results were as follows:

[0159] Physical and chemical properties: yellow solid, melting point 130-131 °C, yield 42%.

[0160] Infrared spectrum: IR cm -1 (KBr): 3730, 2926, 2354, 1653, 1487, 1340, 733.

[0161] Nuclear magnetic resonance hydrogen spectrum: 1 H NMR (400 MHz, CDC13) δ: 7.87 (d, J = 8.4 Hz, 2H), 7.62 (s, 1H), 7.31-7.33 (m, 3H), 4.90 (dd, J = 4.0 Hz, 12.8 Hz, 1H), 4.03 (s, 1H), 3.33-3.39 (m, 1H), 2.84-2.92 (m, 2H), 2.56-2.68 (m, 2H), 2.14-2.20 (m, 2H), 1.98-2.06 (m, 2H), 1.70-1.93 (m, 6H), 1.39-1.58 (m, 5H).

[0162] The chemical structural formula is shown as formula IV-15:

[0163] Example 16:

[0164] The present example gives a preparation method of imidazo[1,2-a]pyrimidine matrine derivatives, which is basically the same as example 1, the difference is that: in step three, the α-bromo aromatic ketone is different. In the present example, the α-bromo aromatic ketone is m-bromo-α-bromoacetophenone.

[0165] In the present example, the target compound IV-16 prepared in step three was subjected to physical and chemical property and characterization analysis, and the results were as follows:

[0166] Physical and chemical properties: yellow solid, melting point 222-224℃, yield 38%.

[0167] Infrared spectrum: IR cm -1 (KBr): 3726, 2924, 2352, 1659, 1490, 1343, 717.

[0168] Nuclear magnetic resonance hydrogen spectrum: 1 H NMR (400 MHz, CDCl3) δ: 8.11-8.12 (m, 1H), 7.83-7.85 (m, 1H), 7.64 (s, 1H), 7.34-7.36 (m, 1H), 7.33 (s, 1H), 7.24 (t, J = 7.6 Hz, 1H), 4.91 (dd, J = 4.4 Hz, 13.2 Hz, 1H), 4.03 (s, 1H), 3.39 (t, J = 12.8 Hz, 1H), 2.84-2.91 (m, 2H), 2.56-2.70 (m, 2H), 2.13-2.19 (m, 2H), 1.97-2.03 (m, 2H), 1.69-1.93 (m, 6H), 1.38-1.58 (m, 5H).

[0169] The chemical structural formula is shown as formula IV-16:

[0170] Example 17:

[0171] The present example gives a preparation method of imidazo[1,2-a]pyrimidine matrine derivatives, which is basically the same as example 1, the difference is that: in step three, the α-bromo aromatic ketone is different. In the present example, the α-bromo aromatic ketone is p-bromo-α-bromoacetophenone.

[0172] In the present example, the target compound IV-17 prepared in step three was subjected to physical and chemical property and characterization analysis, and the results were as follows:

[0173] Physical and chemical properties: yellow solid, melting point 157-158℃, yield 56%.

[0174] Infrared spectrum: IR cm-1 (KBr):3684,2926,2363,1653,1484,1340,727.

[0175] H NMR spectrum: 1 H NMR (400MHz, CDCl3) δ: 7.80 (d, J = 8.8Hz, 2H), 7.62 (s, 1H), 7.48 (d, J = 8.4Hz, 2H), 7.31 (s, 1H), 4.91 (dd, J = 4.4Hz, 13.2Hz, 1H), 4.06 (s, 1H) ,3.42(t,J=12.8Hz,1H),2.88-2.95(m,2H),2.55-2.68(m,2H),2.13- 2.25(m,2H),2.03-2.06(m,2H),1.70-1.93(m,6H),1.40-1.58(m,5H).

[0176] Its chemical structure is shown in Formula IV-17:

[0177] Example 18:

[0178] This example provides a method for preparing an imidazo[1,2-a]pyrimidine matrine derivative, which is substantially the same as that of Example 1, except that in step 3, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is o-trifluoromethyl-α-bromoacetophenone.

[0179] In this example, the target compound IV-18 obtained in step 3 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0180] Physical and chemical properties: yellow solid, melting point 119-120°C, yield 48%.

[0181] Infrared spectrum: IR cm -1 (KBr):3682,2930,1653,1489,1440,1309,767.

[0182] H NMR spectrum: 1H NMR (400 MHz, CDC13) δ: 8.22 (d, J = 8.0 Hz, 1H), 7.67-7.71 (m, 2H), 7.59 (t, J = 7.6 Hz, 1H), 7.35-7.39 (m, 2H), 4.91 (dd, J = 4.4 Hz, 12.8 Hz, 1H), 3.99-4.05 (m, 1H), 3.38 (t, J = 12.8 Hz, 1H), 2.82-2.90 (m, 2H), 2.57-2.71 (m, 2H), 2.13-2.21 (m, 2H), 1.95-2.04 (m, 2H), 1.67-1.93 (m, 6H), 1.39-1.58 (m, 5H).

[0183] The chemical structural formula is shown in formula IV-18.

[0184] Example 19:

[0185] This example gives a preparation method of imidazo[1,2-a]pyrimidine matrine derivative, which is basically the same as example 1, the difference is that in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is m-trifluoromethyl-α-bromoacetophenone.

[0186] In this example, the target compound IV-19 prepared in step three was subjected to physical and chemical property and characterization analysis, and the results were as follows:

[0187] Physical and chemical properties: yellow solid, melting point 127-128°C, yield 35%.

[0188] Infrared spectrum: IR cm -1 (KBr): 3684, 2931, 1657, 1491, 1322, 1119, 699.

[0189] Nuclear magnetic resonance hydrogen spectrum: 1 H NMR (400 MHz, CDC13) δ: 8.22 (s, 1H), 8.08-8.10 (m, 1H), 7.66 (s, 1H), 7.46-7.48 (m, 2H), 7.40 (s, 1H), 4.92 (dd, J = 4.0 Hz, 13.2 Hz, 1H), 4.06 (s, 1H), 3.42 (t, J = 12.4 Hz, 1H), 2.90 (s, 2H), 2.57-2.69 (m, 2H), 1.76-2.24 (m, 10H), 1.41-1.60 (m, 5H).

[0190] The chemical structural formula is shown in formula IV-19.

[0191] Example 20:

[0192] The embodiment provides a preparation method of an imidazo[1,2-a]pyrimidine matrine derivative, and the method is basically same as that in Embodiment 1, and the difference is that in step three, the alpha-bromo aromatic ketone is different. In the embodiment, the alpha-bromo aromatic ketone is p-trifluoromethyl-alpha-bromoacetophenone.

[0193] In the embodiment, physical and chemical properties and characterization analysis are carried out on the target compound IV-20 prepared in step three, and the results are as follows:

[0194] Physical and chemical properties: yellow solid, melting point 187-188 DEG C, and the yield is 55%.

[0195] Infrared spectrum: IR cm -1 (KBr): 3693, 2932, 2354, 1658, 1489, 1323, 848.

[0196] Nuclear magnetic resonance hydrogen spectrum: 1 H NMR (400 MHz, CDCl3) δ: 8.04 (d, J = 8.4 Hz, 2H), 7.65 (s, 1H), 7.62 (d, J = 8.0 Hz, 2H), 7.40 (s, 1H), 4.92 (dd, J = 4.4 Hz, 13.2 Hz, 1H), 4.06 (s, 1H), 3.42 (t, J = 12.4 Hz, 1H), 2.90-2.91 (m, 2H), 2.57-2.70 (m, 2H), 2.14-2.23 (m, 2H), 2.03-2.06 (m, 2H), 1.71-1.93 (m, 6H), 1.41-1.59 (m, 5H).

[0197] The chemical structural formula is as shown in formula IV-20:

[0198] Embodiment 21:

[0199] The embodiment provides a preparation method of an imidazo[1,2-a]pyrimidine matrine derivative, and the method is basically same as that in Embodiment 1, and the difference is that in step three, the alpha-bromo aromatic ketone is different. In the embodiment, the alpha-bromo aromatic ketone is p-trifluoromethyl-alpha-bromoacetophenone.

[0200] In the embodiment, physical and chemical properties and characterization analysis are carried out on the target compound IV-20 prepared in step three, and the results are as follows:

[0201] Physical and chemical properties: yellow solid, melting point 187-188 DEG C, and the yield is 55%.

[0202] Infrared spectrum: IR cm -1(KBr):3715,2928,2355,1655,1489,1346,885.

[0203] H NMR spectrum: 1 H NMR (400MHz, CDCl3) δ: 8.24-8.26 (m, 1H), 7.54-7.61 (m, 3H), 7.33-7.37 (m, 1H), 7.26 (s, 1H), 4.90 (dd, J = 4.4Hz, 13.2Hz, 1H), 4.00-4.05 (m, 1 H),3.38(t,J=12.8Hz,1H),2.82-2.90(m,2H),2.56-2.70(m,2H),2.13 -2.20(m,2H),1.96-2.05(m,2H),1.67-1.92(m,6H),1.38-1.58(m,5H).

[0204] Its chemical structure is shown in Formula IV-21:

[0205] Example 22:

[0206] This example provides a method for preparing an imidazo[1,2-a]pyrimidine matrine derivative, which is substantially the same as that of Example 1, except that in step 3, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is m-nitro-α-bromoacetophenone.

[0207] In this example, the target compound IV-22 obtained in step 3 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0208] Physical and chemical properties: yellow solid, melting point 158-159°C, yield 47%.

[0209] Infrared spectrum: IR cm -1 (KBr):3693,2928,2356,1656,1491,1341,721.

[0210] H NMR spectrum: 1H NMR (400 MHz, CDC13) δ: 8.70-8.71 (m, 1H), 8.30-8.32 (m, 1H), 8.06-8.08 (m, 1H), 7.68 (s, 1H), 7.54 (t, J = 8.0 Hz, 1H), 7.46 (s, 1H), 4.92 (dd, J = 4.4 Hz, 12.8 Hz, 1H), 4.04 (s, 1H), 3.40 (t, J = 12.8 Hz, 1H), 2.83-2.90 (m, 2H), 2.58-2.72 (m, 2H), 2.16-2.22 (m, 2H), 1.97-2.02 (m, 2H), 1.68-1.93 (m, 6H), 1.40-1.59 (m, 5H).

[0211] The chemical structure is shown as formula IV-22:

[0212] Example 23:

[0213] This example gives a preparation method of imidazo[1,2-a]pyrimidine matrine derivative, which is basically the same as example 1, the difference is that in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is p-nitro-α-bromoacetophenone.

[0214] In this example, the target compound IV-23 prepared in step three was analyzed for physical and chemical properties and characterization, and the results are as follows:

[0215] Physical and chemical properties: yellow solid, melting point 222-224°C, yield 45%.

[0216] Infrared spectrum: IR cm -1 (KBr): 3692, 2926, 2356, 1657, 1495, 1332, 854.

[0217] Nuclear magnetic resonance hydrogen spectrum: 1 H NMR (400 MHz, CDC13) δ: 8.70-8.71 (m, 1H), 8.30-8.32 (m, 1H), 8.06-8.08 (m, 1H), 7.68 (s, 1H), 7.54 (t, J = 8.0 Hz, 1H), 7.46 (s, 1H), 4.92 (dd, J = 4.4 Hz, 12.8 Hz, 1H), 4.04 (s, 1H), 3.40 (t, J = 12.8 Hz, 1H), 2.83-2.90 (m, 2H), 2.58-2.72 (m, 2H), 2.16-2.22 (m, 2H), 1.97-2.02 (m, 2H), 1.68-1.93 (m, 6H), 1.40-1.59 (m, 5H).

[0218] The chemical structural formula is shown as formula IV-23.

[0219] Example 24

[0220] This example gives a preparation method of imidazo[1,2-a]pyrimidine matrine derivative, which is basically same as example 1, the difference is that: in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is 2,5-difluoro-α-bromoacetophenone.

[0221] In this example, the physical and chemical properties and characterization analysis of the target compound IV-24 prepared in step three are carried out, and the results are as follows:

[0222] Physical and chemical properties: yellow solid, melting point 135-137℃, yield 43%.

[0223] Infrared spectrum: IR cm -1 (KBr): 3680, 2929, 1656, 1489, 1341, 882.

[0224] Nuclear magnetic resonance hydrogen spectrum: 1 H NMR (400 MHz, CDCl3) δ: 8.11-8.16 (m, 1H), 7.65 (s, 1H), 7.55 (d, J = 4.4 Hz, 1H), 6.98-7.04 (m, 1H), 6.83-6.89 (m, 1H), 4.92 (dd, J = 4.4 Hz, 12.8 Hz, 1H), 4.03 (s, 1H), 3.40 (t, J = 12.8 Hz, 1H), 2.83-2.88 (m, 2H), 2.57-2.71 (m, 2H), 2.14-2.21 (m, 2H), 2.00-2.04 (m, 2H), 1.69-1.93 (m, 6H), 1.39-1.58 (m, 5H).

[0225] The chemical structural formula is shown as formula IV-24:

[0226] Example 25

[0227] This example gives a preparation method of imidazo[1,2-a]pyrimidine matrine derivative, which is basically same as example 1, the difference is that: in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is 3,4-dichloro-α-bromoacetophenone.

[0228] In this example, the physical and chemical properties and characterization analysis of the target compound IV-25 prepared in step three are carried out, and the results are as follows:

[0229] Physical and chemical properties: yellow solid, melting point 150-151 °C, yield 50%.

[0230] Infrared spectrum: IR cm -1 (KBr): 3678, 2926, 2354, 1653, 1487, 1342, 884.

[0231] Nuclear magnetic resonance hydrogen spectrum: 1 H NMR (400 MHz, CDCI3) δ: 8.05 (d, J = 2.0 Hz, 1H), 7.74 (dd, J = 2.0 Hz, 8.4 Hz, 1H), 7.63 (s, 1H), 7.42 (d, J = 8.4 Hz, 1H), 7.31 (s, 1H), 4.90 (dd, J = 4.4 Hz, 12.8 Hz, 1H), 4.02-4.04 (m, 1H), 3.39 (t, J = 12.8 Hz, 1H), 2.83-2.91 (m, 2H), 2.56-2.70 (m, 2H), 2.13-2.20 (m, 2H), 1.97-2.05 (m, 2H), 1.69-1.92 (m, 6H), 1.39-1.58 (m, 5H).

[0232] The chemical structural formula is shown as formula IV-25:

[0233] Example 26:

[0234] This example gives a preparation method of imidazo[1,2-a]pyrimidine matrine derivative, which is basically the same as example 1, the difference is that in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is p-trifluoromethoxy-α-bromoacetophenone.

[0235] In this example, the physical and chemical properties and characterization analysis of the target compound IV-26 prepared in step three were carried out, and the results were as follows:

[0236] Physical and chemical properties: yellow solid, melting point 132-133 °C, yield 36%.

[0237] Infrared spectrum: IR cm -1 (KBr): 3683, 2931, 2354, 1657, 1487, 1346, 851.

[0238] Nuclear magnetic resonance hydrogen spectrum: 1H NMR (400 MHz, CDC13) δ: 7.95 (d, J = 8.4 Hz, 2H), 7.64 (s, 1H), 7.32 (s, 1H), 7.22 (d, J = 8.4 Hz, 2H), 4.91 (dd, J = 4.8 Hz, 13.2 Hz, 1H), 4.00-4.05 (m, 1H), 3.39 (t, J = 12.8 Hz, 1H), 2.83-2.91 (m, 2H), 2.56-2.70 (m, 2H), 2.13-2.19 (m, 2H), 1.97-2.05 (m, 2H), 1.68-1.93 (m, 6H), 1.38-1.58 (m, 5H).

[0239] The chemical structure is shown as formula IV-26:

[0240] Example 27:

[0241] This example gives a preparation method of imidazo[1,2-a]pyrimidine matrine derivative, which is basically the same as example 1, the difference is that in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is α-bromo-1-naphthaldehyde.

[0242] In this example, the physical and chemical properties and characterization analysis of the target compound IV-27 prepared in step three are carried out, and the results are as follows:

[0243] Physical and chemical properties: yellow solid, melting point 154-155°C, yield 40%.

[0244] Infrared spectrum: IR cm -1 (KBr): 3689, 2924, 2364, 1652, 1486, 1339, 776.

[0245] Nuclear magnetic resonance hydrogen spectrum: 1 H NMR (400 MHz, CDC13) δ: 7.95 (d, J = 8.4 Hz, 2H), 7.64 (s, 1H), 7.32 (s, 1H), 7.22 (d, J = 8.4 Hz, 2H), 4.91 (dd, J = 4.8 Hz, 13.2 Hz, 1H), 4.00-4.05 (m, 1H), 3.39 (t, J = 12.8 Hz, 1H), 2.83-2.91 (m, 2H), 2.56-2.70 (m, 2H), 2.13-2.19 (m, 2H), 1.97-2.05 (m, 2H), 1.68-1.93 (m, 6H), 1.38-1.58 (m, 5H).

[0246] The chemical structural formula is shown as formula IV-27:

[0247] Example 28:

[0248] This example gives a preparation method of imidazo[1,2-a]pyrimidine matrine derivatives, which is basically the same as example 1, the difference is that in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is α-bromo-2-naphthaldehyde.

[0249] In this example, the physical and chemical properties and characterization analysis of the target compound IV-28 prepared in step three are carried out, and the results are as follows:

[0250] Physical and chemical properties: yellow solid, melting point 146-148℃, yield 40%.

[0251] Infrared spectrum: IR cm -1 (KBr): 3716, 2625, 2356, 1651, 1485, 1340, 818.

[0252] Nuclear magnetic resonance hydrogen spectrum: 1 H NMR (400 MHz, CDCI3) δ: 8.54 (s, 1H), 7.92-7.95 (m, 1H), 7.85-7.87 (m, 1H), 7.78-7.82 (m, 2H), 7.63 (s, 1H), 7.39-7.46 (m, 3H), 4.93 (dd, J = 4.4 Hz, 12.8 Hz, 1H), 3.99-4.05 (m, 1H), 3.39 (t, J = 12.8 Hz, 1H), 2.83-2.91 (m, 2H), 2.53-2.67 (m, 2H), 2.11-2.18 (m, 2H), 1.96-2.04 (m, 2H), 1.65-1.91 (m, 6H), 1.37-1.57 (m, 5H).

[0253] The chemical structural formula is shown as formula IV-28:

[0254] Example 29:

[0255] This example gives a preparation method of imidazo[1,2-a]pyrimidine matrine derivatives, which is basically the same as example 1, the difference is that in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is α-bromo-2-naphthaldehyde.

[0256] In step one, the temperature is raised to 60℃ and stirred for 5h; the solid product prepared is intermediate II-2.

[0257] The product prepared in step one was subjected to physical and chemical property and characterization analysis in this example, and the results were as follows:

[0258] Physical and chemical property: yellow solid, melting point 98-99°C, yield 70%.

[0259] Infrared spectrum: IR cm -1 (KBr): 3727, 2933, 2354, 1557, 1286, 1207, 663.

[0260] Nuclear magnetic resonance hydrogen spectrum: 1 H NMR (400 MHz, CDCI3) δ: 9.69 (s, 1H), 3.65-3.69 (m, 1H), 3.29-3.34 (m, 1H), 3.16 (t, J = 11.6 Hz, 1H), 2.90-2.94 (m, 1H), 2.80-2.86 (m, 1H), 2.24-2.45 (m, 5H), 2.06-2.17 (m, 1H), 1.84-1.95 (m, 5H), 1.51-1.78 (m, 5H), 1.04-1.15 (m, 1H).

[0261] In step two, heating was carried out under reflux for 12 h; the solid product prepared was intermediate III-2.

[0262] The product prepared in step two was subjected to physical and chemical property and characterization analysis in this example, and the results were as follows:

[0263] Physical and chemical property: yellow solid, melting point 138-140°C, yield 76%.

[0264] Infrared spectrum: IR cm -1 (KBr): 3337, 3200, 2928, 1644, 1602, 1553, 1454, 1328.

[0265] Nuclear magnetic resonance hydrogen spectrum: 1 H NMR (400 MHz, CDCI3) δ: 7.48 (s, 1H), 4.60 (s, 2H), 3.53 (dd, J = 5.2 Hz, 13.2 Hz, 1H), 3.37-3.43 (m, 1H), 3.29-3.34 (m, 1H), 2.85-2.89 (m, 1H), 2.74-2.80 (m, 1H), 2.42-2.54 (m, 2H), 2.13-2.23 (m, 2H), 1.97-2.06 (m, 3H), 1.78-1.95 (m, 3H), 1.65-1.77 (m, 1H), 1.47-1.63 (m, 5H), 1.06-1.17 (m, 1H).

[0266] In step three, the solid product prepared was the target compound IV-29. In this example, the α-bromo aromatic ketone was α-bromoacetophenone.

[0267] In this example, the target compound IV-29 prepared in step three was subjected to physical and chemical property and characterization analysis, and the results were as follows:

[0268] Physical and chemical properties: yellow solid, melting point 125-127 °C, yield 70%.

[0269] Infrared spectrum: IR cm -1 (KBr): 3693, 2926, 2353, 1657, 1476, 1340, 704.

[0270] Nuclear magnetic resonance hydrogen spectrum: 1 H NMR (400 MHz, CDCI3) δ: 7.95 (d, J = 7.6 Hz, 2H), 7.61 (s, 1H), 7.38 (t, J = 7.6 Hz, 2H), 7.32 (s, 1H), 7.22-7.24 (m, 1H), 3.74 (dd, J = 4.8 Hz, 14.0 Hz, 1H), 3.49-3.55 (m, 2H), 2.87-2.90 (m, 1H), 2.77-2.82 (m, 1H), 2.55-2.68 (m, 2H), 2.00-2.22 (m, 6H), 1.88-1.96 (m, 3H), 1.50-1.76 (m, 5H), 1.10-1.19 (m, 1H).

[0271] The chemical structural formula is shown in formula IV-29:

[0272] Example 30:

[0273] This example gives a preparation method of imidazo[1,2-a]pyrimidine sophoridine derivative, which is basically the same as example 28, the difference is that in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is o-methyl-α-bromoacetophenone.

[0274] In this example, the target compound IV-30 prepared in step three was subjected to physical and chemical property and characterization analysis, and the results were as follows:

[0275] Physical and chemical properties: yellow solid, melting point 120-122 °C, yield 60%.

[0276] Infrared spectrum: IR cm -1 (KBr): 3674, 2923, 2353, 1654, 1470, 1340, 728.

[0277] H NMR spectrum: 1 H NMR(400MHz, CDCl3)δ:8.14(d,J=8.8Hz,1H),7.68(s,1H),7.16-7.24(m,4H),3.75(dd,J=5.2Hz,13.6Hz,1H),3.53-3.59(m,2H) ,2.80-2.92(m,2H),2.59-2.72(m,2H),2.54(s,3H),2.09-2.22(m,5H),1.89-1.93(m,3H),1.57-1.75(m,6H),1.10-1.21(m,1H).

[0278] Its chemical structure is shown in Formula IV-30:

[0279] Example 31:

[0280] This example provides a method for preparing an imidazo[1,2-a]pyrimidine sophoridine derivative. This method is essentially the same as that of Example 28, except that in step 3, the α-bromoaromatic ketone is different. In this example, the α-bromoaromatic ketone is m-methyl-α-bromoacetophenone.

[0281] In this example, the target compound IV-31 obtained in step 3 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0282] Physical and chemical properties: yellow solid, melting point 129-130°C, yield 45%.

[0283] Infrared spectrum: IR cm -1 (KBr):2926,2357,1653,1465,1343,764.

[0284] H NMR spectrum: 1H NMR (400 MHz, CDC13) δ: 7.84 (s, 1H), 7.71 (d, J = 7.6 Hz, 1H), 7.63 (s, 1H), 7.33-7.34 (m, 1H), 7.26-7.27 (m, 0.27H), 7.23-7.25 (m, 0.86H), 7.07 (d, J = 7.2 Hz, 1H), 3.74 (dd, J = 5.2 Hz, 14.0 Hz, 1H), 3.51-3.57 (m, 2H), 2.89-2.92 (m, 1H), 2.79-2.83 (m, 1H), 2.57-2.70 (m, 2H), 2.38 (s, 3H), 2.03-2.24 (m, 5H), 1.88-1.91 (m, 3H), 1.55-1.75 (m, 6H), 1.10-1.20 (m, 1H).

[0285] The chemical structure is shown as formula IV-31.

[0286] Example 32

[0287] This example gives a preparation method of imidazo[1,2-a]pyrimidine sophoridine derivative, which is basically the same as example 28, the difference is that in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is p-methyl-α-bromoacetophenone.

[0288] In this example, the target compound IV-32 prepared in step three was subjected to physical and chemical property and characterization analysis, and the results were as follows:

[0289] Physical and chemical properties: yellow solid, melting point 138-140°C, yield 48%.

[0290] Infrared spectrum: IR cm -1 (KBr): 3696, 2924, 2356, 1656, 1469, 1340, 822.

[0291] Nuclear magnetic resonance hydrogen spectrum: 1H NMR (400 MHz, CDCI3) δ: 7.84 (d, J = 8.0 Hz, 2H), 7.61 (s, 1H), 7.29 (s, 1H), 7.19 (d, J = 8.0 Hz, 2H), 3.73 (dd, J = 5.2 Hz, 14.0 Hz, 1H), 3.50-3.56 (m, 2H), 2.89-2.92 (m, 1H), 2.79-2.84 (m, 1H), 2.56-2.69 (m, 2H), 2.35 (s, 3H), 2.00-2.26 (m, 6H), 1.83-1.97 (m, 3H), 1.55-1.79 (m, 5H), 1.09-1.20 (m, 1H).

[0292] The chemical structure is shown as formula IV-32:

[0293] Example 33:

[0294] This example gives a preparation method of imidazo[1,2-a]pyrimidine sophoridine derivative, which is basically the same as example 28, the difference is that in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is o-methoxy-α-bromoacetophenone.

[0295] In this example, the physical and chemical properties and characterization analysis of the target compound IV-33 prepared in step three were carried out, and the results were as follows:

[0296] Physical and chemical properties: yellow solid, melting point 137-139°C, yield 36%.

[0297] Infrared spectrum: IR cm -1 (KBr): 3673, 2928, 2362, 1656, 1481, 1339, 754.

[0298] Nuclear magnetic resonance hydrogen spectrum: 1 H NMR (500 MHz, CDCI3) δ: 8.51-8.53 (m, 1H), 7.69 (s, 1H), 7.64 (s, 1H), 7.21-7.24 (m, 1H), 7.03-7.06 (m, 1H), 6.95 (d, J = 8.0 Hz, 1H), 3.96 (s, 3H), 3.75 (dd, J = 5.0 Hz, 14.0 Hz, 1H), 3.49-3.57 (m, 2H), 2.88-2.90 (m, 1H), 2.78-2.82 (m, 1H), 2.58-2.69 (m, 2H), 2.01-2.23 (m, 5H), 1.89-1.94 (m, 3H), 1.55-1.74 (m, 6H), 1.11-1.19 (m, 1H).

[0299] The chemical structure is shown as formula IV-33:

[0300] Example 34:

[0301] This example gives a preparation method of imidazo[1,2-a]pyrimidine sophoridine derivative, which is basically the same as example 28, the difference is that in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is m-methoxy-α-bromoacetophenone.

[0302] In this example, the physical and chemical properties and characterization analysis of the target compound IV-34 prepared in step three are carried out, and the results are as follows:

[0303] Physical and chemical properties: yellow solid, melting point 139-140℃, yield 35%.

[0304] Infrared spectrum: IR cm -1 (KBr): 3667, 2926, 1655, 1473, 1343, 871.

[0305] Nuclear magnetic resonance hydrogen spectrum: 1 H NMR (500 MHz, CDCl3) δ: 7.62-7.64 (m, 2H), 7.45 (d, J = 7.5 Hz, 1H), 7.34 (s, 1H), 7.27 (s, 0.49H), 7.24 (s, 0.49H), 6.80-6.82 (m, 1H), 3.86 (s, 3H), 3.75 (dd, J = 4.5 Hz, 13.5 Hz, 1H), 3.55 (s, 2H), 2.83-2.93 (m, 2H), 2.59-2.70 (m, 2H), 1.89-2.24 (m, 8H), 1.58-1.76 (m, 6H), 1.11-1.20 (m, 1H).

[0306] The chemical structure is shown as formula IV-34:

[0307] Example 35:

[0308] This example gives a preparation method of imidazo[1,2-a]pyrimidine sophoridine derivative, which is basically the same as example 28, the difference is that in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is p-methoxy-α-bromoacetophenone.

[0309] In this example, the physical and chemical properties and characterization analysis of the target compound IV-35 prepared in step three are carried out, and the results are as follows:

[0310] Physical and chemical properties: yellow solid, melting point 132-134 °C, yield 52%.

[0311] Infrared spectrum: IR cm -1 (KBr): 3671, 2924, 2351, 1654, 1471, 1343, 886.

[0312] Nuclear magnetic resonance hydrogen spectrum: 1 H NMR (400 MHz, CDCI3) δ: 7.88 (d, J = 8.8 Hz, 2H), 7.63 (s, 1H), 7.25 (s, 1H), 6.93 (d, J = 8.8 Hz, 2H), 3.83 (s, 3H), 3.74 (dd, J = 4.8 Hz, 13.6 Hz, 1H), 3.51-3.57 (m, 2H), 2.87-2.90 (m, 1H), 2.77-2.82 (m, 1H), 2.57-2.70 (m, 2H), 2.13-2.22 (m, 2H), 2.00-2.10 (m, 2H), 1.73-1.97 (m, 6H), 1.55-1.68 (m, 4H), 1.09-1.20 (m, 1H).

[0313] The chemical structural formula is shown as formula IV-35:

[0314] Example 36:

[0315] This example gives a preparation method of imidazo[1,2-a]pyrimidine sophoridine derivative, which is basically the same as example 28, the difference is that in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is p-phenoxy-α-bromoacetophenone.

[0316] In this example, the physical and chemical properties and characterization analysis of the target compound IV-36 prepared in step three were carried out, and the results were as follows:

[0317] Physical and chemical properties: yellow solid, melting point 125-126 °C, yield 48%.

[0318] Infrared spectrum: IR cm -1 (KBr): 3677, 2923, 1654, 1472, 1341, 749.

[0319] Nuclear magnetic resonance hydrogen spectrum: 1H NMR (400 MHz, CDC13) δ: 7.92 (d, J = 8.8 Hz, 2H), 7.64 (s, 1H), 7.29-7.35 (m, 3H), 7.11 (t, J = 7.6 Hz, 1H), 7.01-7.04 (m, 4H), 3.75 (dd, J = 5.2 Hz, 14.0 Hz, 1H), 3.51-3.57 (m, 2H), 2.83-2.93 (m, 2H), 2.59-2.70 (m, 2H), 2.11-2.24 (m, 5H), 1.73-1.92 (m, 4H), 1.58-1.70 (m, 5H), 1.11-1.21 (m, 1H).

[0320] The chemical structural formula is shown in formula IV-36.

[0321] Example 37:

[0322] This example gives a preparation method of imidazo[1,2-a]pyrimidine sophoridine derivative, which is basically the same as example 28, the difference is that in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is o-fluoro-α-bromoacetophenone.

[0323] In this example, the target compound IV-37 prepared in step three was subjected to physical and chemical property and characterization analysis, and the results were as follows:

[0324] Physical and chemical properties: yellow solid, melting point 129-131°C, yield 35%.

[0325] Infrared spectrum: IR cm -1 (KBr): 3685, 2928, 1658, 1480, 1343, 756.

[0326] Nuclear magnetic resonance hydrogen spectrum: 1 H NMR (500 MHz, CDC13) δ: 8.43 (s, 1H), 7.66 (s, 1H), 7.54 (s, 1H), 7.20 (s, 2H), 7.05-7.09 (m, 1H), 3.72-3.74 (m, 1H), 3.53-3.58 (m, 2H), 2.83-2.94 (m, 2H), 2.59-2.70 (m, 2H), 1.90-2.24 (m, 9H), 1.56-1.77 (m, 5H), 1.12-1.20 (m, 1H).

[0327] The chemical structural formula is shown in formula IV-37.

[0328] Example 38:

[0329] The example gives a preparation method of imidazo[1,2-a]pyrimidine sophoridine derivative, the method is basically same as example 28, the difference is that: in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is m-fluoro-α-bromoacetophenone.

[0330] In this example, the physical and chemical properties and characterization analysis of the target compound IV-38 prepared in step three are carried out, and the results are as follows:

[0331] Physical and chemical properties: yellow solid, melting point 126-127℃, yield is 48%.

[0332] Infrared spectrum: IR cm -1 (KBr): 3684, 2926, 1658, 1476, 1342, 873.

[0333] Nuclear magnetic resonance hydrogen spectrum: 1 H NMR (500 MHz, CDCl3) δ: 7.65-7.69 (m, 2H), 7.62 (s, 1H), 7.28-7.32 (m, 2H), 6.91-6.94 (m, 1H), 3.73 (dd, J = 4.5 Hz, 13.5 Hz, 1H), 3.50-3.55 (m, 2H), 2.88-2.90 (m, 1H), 2.77-2.81 (m, 1H), 2.58-2.67 (m, 2H), 2.13-2.22 (m, 3H), 1.88-2.08 (m, 6H), 1.54-1.73 (m, 5H), 1.11-1.17 (m, 1H).

[0334] The chemical structural formula is as shown in formula IV-38:

[0335] Example 39:

[0336] The example gives a preparation method of imidazo[1,2-a]pyrimidine sophoridine derivative, the method is basically same as example 28, the difference is that: in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is p-fluoro-α-bromoacetophenone.

[0337] In this example, the physical and chemical properties and characterization analysis of the target compound IV-39 prepared in step three are carried out, and the results are as follows:

[0338] Physical and chemical properties: yellow solid, melting point 127-129℃, yield is 63%.

[0339] Infrared spectrum: IR cm -1(KBr):3668,2928,1656,1474,1343,839.

[0340] H NMR spectrum: 1 H NMR (500MHz, CDCl3) δ: 7.88-7.91 (m, 2H), 7.62 (s, 1H), 7.27 (s, 1H), 7.06 (t, J = 8.5Hz, 2H), 3.73 (dd, J = 5.0Hz, 14.0Hz, 1H), 3.51-3.56 (m, 2H),2.89-2.91(m,1H),2.80-2.84(m,1H),2.58-2.68(m,2H),2.03-2 .24(m,6H),1.89-1.94(m,3H),1.56-1.74(m,5H),1.11-1.19(m,1H).

[0341] Its chemical structure is shown in Formula IV-39:

[0342] Example 40:

[0343] This example provides a method for preparing an imidazo[1,2-a]pyrimidine sophoridine derivative. This method is essentially the same as that of Example 28, except that in step 3, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is o-chloro-α-bromoacetophenone.

[0344] In this example, the target compound IV-40 obtained in step 3 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0345] Physical and chemical properties: yellow solid, melting point 141-142°C, yield 45%.

[0346] Infrared spectrum: IR cm -1 (KBr):3682,2925,1656,1474,1342,750.

[0347] H NMR spectrum: 1H NMR (400 MHz, CDCI3) δ: 8.52 (d, J = 7.2 Hz, 1 H), 7.87 (s, 1 H), 7.68 (s, 1 H), 7.40 (d, J = 8.0 Hz, 1 H), 7.34 (t, J = 7.6 Hz, 1 H), 7.18 (t, J = 7.2 Hz, 1 H), 3.70-3.74 (m, 1 H), 3.55 (s, 2 H), 2.82-2.93 (m, 2 H), 2.60-2.71 (m, 2 H), 2.07-2.24 (m, 5 H), 1.56-1.91 (m, 9 H), 1.13-1.20 (m, 1 H).

[0348] The chemical structural formula is shown in formula IV-40.

[0349] Example 41

[0350] This example gives a preparation method of imidazo[1,2-a]pyrimidine sophoridine derivative, which is basically the same as example 28, the difference is that in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is m-chloro-α-bromoacetophenone.

[0351] In this example, the target compound IV-41 prepared in step three is subjected to physical and chemical property and characterization analysis, and the results are as follows:

[0352] Physical and chemical properties: yellow solid, melting point 137-139°C, yield 60%.

[0353] Infrared spectrum: IR cm -1 (KBr): 3673, 2926, 1656, 1476, 1343, 750.

[0354] Nuclear magnetic resonance hydrogen spectrum: 1 H NMR (400 MHz, CDCI3) δ: 8.52 (d, J = 7.2 Hz, 1 H), 7.87 (s, 1 H), 7.68 (s, 1 H), 7.40 (d, J = 8.0 Hz, 1 H), 7.34 (t, J = 7.6 Hz, 1 H), 7.18 (t, J = 7.2 Hz, 1 H), 3.70-3.74 (m, 1 H), 3.55 (s, 2 H), 2.82-2.93 (m, 2 H), 2.60-2.71 (m, 2 H), 2.07-2.24 (m, 5 H), 1.56-1.91 (m, 9 H), 1.13-1.20 (m, 1 H).

[0355] The chemical structural formula is shown in formula IV-41.

[0356] Example 42

[0357] This example gives a preparation method of imidazo[1,2-a]pyrimidine sophorin base derivative, which is basically same as example 28, the difference is that: in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is p-chloro-α-bromoacetophenone.

[0358] In this example, the target compound IV-42 prepared in step three was subjected to physical and chemical properties and characterization analysis, and the results were as follows:

[0359] Physical and chemical properties: yellow solid, melting point 200-201℃, yield 46%.

[0360] Infrared spectrum: IR cm- 1 (KBr): 3672, 2923, 2349, 1654, 1465, 1340, 831.

[0361] Nuclear magnetic resonance hydrogen spectrum: 1 H NMR (400 MHz, CDCI3) δ: 7.88 (d, J = 8.8 Hz, 2H), 7.62 (s, 1H), 7.33 (d, J = 8.4 Hz, 2H), 7.30 (s, 1H), 3.74 (dd, J = 5.2 Hz, 14.0 Hz, 1H), 3.50-3.56 (m, 2H), 2.89-2.92 (m, 1H), 2.79-2.84 (m, 1H), 2.57-2.70 (m, 2H), 2.07-2.24 (m, 5H), 1.88-1.98 (m, 3H), 1.55-1.75 (m, 6H), 1.09-1.20 (m, 1H).

[0362] The chemical structural formula is shown as formula IV-42:

[0363] Example 43

[0364] This example gives a preparation method of imidazo[1,2-a]pyrimidine sophorin base derivative, which is basically same as example 28, the difference is that: in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is o-bromo-α-bromoacetophenone.

[0365] In this example, the target compound IV-43 prepared in step three was subjected to physical and chemical properties and characterization analysis, and the results were as follows:

[0366] Physical and chemical properties: yellow solid, melting point 218-220℃, yield 53%.

[0367] Infrared spectrum: IR cm- 1 (KBr):3686,2922,1655,1475,1339,770.

[0368] H NMR spectrum: 1 H NMR (400 MHz, CDCl3) δ:8.41-8.44(m,1H),7.94(s,1H),7.68(s,1H),7.59-7.61(m,1H),7.34-7.38(m,1H),7.06-7.11(m,1H),3.75(dd,J=4.8 Hz,14.0Hz,1H),3.52-3.57(m,2H),2.90-2.92(m,1H),2.80-2.84(m,1H),2.58-2.72 (m,2H),2.08-2.24(m,5H),1.89-1.98(m,3H),1.56-1.75(m,6H),1.10-1.20(m,1H).

[0369] Its chemical structure is shown in Formula IV-43:

[0370] Example 44:

[0371] This example provides a method for preparing an imidazo[1,2-a]pyrimidine sophoridine derivative. This method is essentially the same as that of Example 28, except that in step 3, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is m-bromo-α-bromoacetophenone.

[0372] In this example, the target compound IV-44 obtained in step 3 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0373] Physical and chemical properties: yellow solid, melting point 136-138°C, yield 44%.

[0374] Infrared spectrum: IR cm -1 (KBr):3673,2925,1655,1472,1340,722.

[0375] H NMR spectrum: 1H NMR (500 MHz, CDC13) δ: 8.12 (s, 1H), 7.86 (d, J = 8.0 Hz, 1H), 7.64 (s, 1H), 7.33-7.36 (m, 2H), 7.20-7.24 (m, 1H), 3.71-3.74 (m, 1H), 3.54 (s, 2H), 2.84-2.93 (m, 2H), 2.59-2.69 (m, 2H), 2.13-2.24 (m, 5H), 1.89-1.92 (m, 3H), 1.58-1.74 (m, 6H), 1.12-1.19 (m, 1H).

[0376] The chemical structural formula is shown in formula IV-44.

[0377] Example 45

[0378] This example gives a preparation method of imidazo[1,2-a]pyrimidine sophoridine derivative, which is basically the same as example 28, the difference is that in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is p-bromo-α-bromoacetophenone.

[0379] In this example, the target compound IV-45 prepared in step three was subjected to physical and chemical property and characterization analysis, and the results were as follows:

[0380] Physical and chemical properties: yellow solid, melting point 145-147°C, yield 50%.

[0381] Infrared spectrum: IR cm -1 (KBr): 3665, 2925, 1654, 1463, 1341, 829.

[0382] Nuclear magnetic resonance hydrogen spectrum: 1 H NMR (500 MHz, CDC13) δ: 8.12 (s, 1H), 7.86 (d, J = 8.0 Hz, 1H), 7.64 (s, 1H), 7.33-7.36 (m, 2H), 7.20-7.24 (m, 1H), 3.71-3.74 (m, 1H), 3.54 (s, 2H), 2.84-2.93 (m, 2H), 2.59-2.69 (m, 2H), 2.13-2.24 (m, 5H), 1.89-1.92 (m, 3H), 1.58-1.74 (m, 6H), 1.12-1.19 (m, 1H).

[0383] The chemical structural formula is shown in formula IV-45.

[0384] Example 46:

[0385] This example gives a preparation method of imidazo[1,2-a]pyrimidine sparteine derivative, which is basically the same as that of example 28, the difference is that in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is o-trifluoromethyl-α-bromoacetophenone.

[0386] In this example, the target compound IV-46 prepared in step three was subjected to physical and chemical property and characterization analysis, and the results were as follows:

[0387] Physical and chemical properties: yellow solid, melting point 212-214°C, yield 42%.

[0388] Infrared spectrum: IR cm -1 (KBr): 3686, 2930, 1659, 1475, 1309, 772.

[0389] Nuclear magnetic resonance hydrogen spectrum: 1 H NMR (400 MHz, CDCI3) δ: 8.26 (d, J = 7.6 Hz, 1H), 7.67-7.71 (m, 2H), 7.59 (t, J = 7.6 Hz, 1H), 7.35-7.38 (m, 2H), 3.75 (dd, J = 5.2 Hz, 14.0 Hz, 1H), 3.52-3.58 (m, 2H), 2.89-2.92 (m, 1H), 2.78-2.84 (m, 1H), 2.59-2.72 (m, 2H), 1.89-2.24 (m, 9H), 1.51-1.78 (m, 5H), 1.10-1.20 (m, 1H).

[0390] The chemical structural formula is shown as formula IV-46:

[0391] Example 47:

[0392] This example gives a preparation method of imidazo[1,2-a]pyrimidine sparteine derivative, which is basically the same as that of example 28, the difference is that in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is m-trifluoromethyl-α-bromoacetophenone.

[0393] In this example, the target compound IV-47 prepared in step three was subjected to physical and chemical property and characterization analysis, and the results were as follows:

[0394] Physical and chemical properties: yellow solid, melting point 128-129°C, yield 48%.

[0395] Infrared spectrum: IR cm -1(KBr):3676,2928,1657,1481,1322,699.

[0396] H NMR spectrum: 1 H NMR (400MHz, CDCl3) δ: 8.24 (s, 1H), 8.09-8.10 (m, 1H), 7.66 (s, 1H), 7.44-7.48 (m, 2H), 7.40 (s, 1H), 3.76 (dd, J = 5.2Hz, 14.0Hz, 1H), 3.52-3.58(m,2H),2.90-2.93(m,1H),2.81-2.85(m,1H),2.59-2.72(m,2H),1.89-2.25(m,9H),1.56-1.80(m,5H),1.10-1.20(m,1H).

[0397] Its chemical structure is shown in Formula IV-47:

[0398] Example 48:

[0399] This example provides a method for preparing an imidazo[1,2-a]pyrimidine sophoridine derivative. This method is essentially the same as that of Example 28, except that in step 3, the α-bromoaromatic ketone is different. In this example, the α-bromoaromatic ketone is p-trifluoromethyl-α-bromoacetophenone.

[0400] In this example, the target compound IV-48 obtained in step 3 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0401] Physical and chemical properties: yellow solid, melting point 144-146°C, yield 42%.

[0402] Infrared spectrum: IR cm -1 (KBr):3675,2930,1659,1476,1322,847.

[0403] H NMR spectrum: 1H NMR (400 MHz, CDCI3) δ: 8.05 (d, J = 8.4 Hz, 2H), 7.65 (s, 1 H), 7.62 (d, J = 8.4 Hz, 2H), 7.40 (s, 1 H), 3.75 (dd, J = 4.8 Hz, 13.6 Hz, 1 H), 3.49-3.57 (m, 2H), 2.89-2.92 (m, 1 H), 2.79-2.84 (m, 1 H), 2.58-2.72 (m, 2H), 2.12-2.24 (m, 3H), 2.03-2.09 (m, 2H), 1.78-2.00 (m, 4H), 1.52-1.78 (m, 5H), 1.10-1.20 (m, 1 H).

[0404] The chemical structure of the compound is shown as formula IV-48.

[0405] Example 48

[0406] This example gives a method for preparing an imidazo[1,2-a]pyrimidine sophoridine derivative. The method is basically the same as that in Example 28, except that in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is o-nitro-α-bromoacetophenone.

[0407] In this example, the physical and chemical properties and characterization analysis of the target compound IV-49 prepared in step three were carried out, and the results are as follows:

[0408] Physical and chemical properties: yellow solid, melting point 141-143 °C, yield 36%.

[0409] Infrared spectrum: IR cm -1 (KBr): 3677, 2925, 1656, 1478, 1348, 718.

[0410] Nuclear magnetic resonance hydrogen spectrum: 1 H NMR (400 MHz, CDCI3) δ: 8.05 (d, J = 8.4 Hz, 2H), 7.65 (s, 1 H), 7.62 (d, J = 8.4 Hz, 2H), 7.40 (s, 1 H), 3.75 (dd, J = 4.8 Hz, 13.6 Hz, 1 H), 3.49-3.57 (m, 2H), 2.89-2.92 (m, 1 H), 2.79-2.84 (m, 1 H), 2.58-2.72 (m, 2H), 2.12-2.24 (m, 3H), 2.03-2.09 (m, 2H), 1.78-2.00 (m, 4H), 1.52-1.78 (m, 5H), 1.10-1.20 (m, 1 H).

[0411] The chemical structure of the compound is shown as formula IV-49.

[0412] Example 50

[0413] This example gives a preparation method of imidazo[1,2-a]pyrimidine sophorin base derivative, which is basically same as example 28, the difference is that: in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is m-nitro-α-bromoacetophenone.

[0414] In this example, the physicochemical properties and characterization analysis of the target compound IV-50 prepared in step three are carried out, and the results are as follows:

[0415] Physicochemical properties: red solid, melting point 138-139℃, yield 46%.

[0416] Infrared spectrum: IR cm -1 (KBr): 3671, 2926, 1655, 1477, 1341, 727.

[0417] Nuclear magnetic resonance hydrogen spectrum: 1 H NMR (400 MHz, CDCI3) δ: 8.72 (s, 1H), 8.32 (d, J = 7.6 Hz, 1H), 8.08 (d, J = 7.6 Hz, 1H), 7.68 (s, 1H), 7.54 (t, J = 8.0 Hz, 1H), 7.46 (s, 1H), 3.72-3.76 (m, 1H), 3.51-3.56 (m, 2H), 2.78-2.91 (m, 2H), 2.61-2.73 (m, 2H), 1.89-2.19 (m, 6H), 1.57-1.72 (m, 8H), 1.14-1.19 (m, 1H).

[0418] The chemical structural formula is shown as formula IV-50:

[0419] Example 51

[0420] This example gives a preparation method of imidazo[1,2-a]pyrimidine sophorin base derivative, which is basically same as example 28, the difference is that: in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is p-nitro-α-bromoacetophenone.

[0421] In this example, the physicochemical properties and characterization analysis of the target compound IV-51 prepared in step three are carried out, and the results are as follows:

[0422] Physicochemical properties: red solid, melting point 217-219℃, yield 45%.

[0423] Infrared spectrum: IR cm -1 (KBr): 2926, 1656, 1597, 1491, 1330, 717.

[0424] Nuclear magnetic resonance hydrogen spectrum: 1 H NMR (400 MHz, CDCI3) δ: 8.23 (d, J = 8.8 Hz, 2H), 8.08 (d, J = 8.8 Hz, 2H), 7.67 (s, 1H), 7.48 (s, 1H), 3.76 (dd, J = 4.8 Hz, 14.0 Hz, 1H), 3.51-3.59 (m, 2H), 2.77-2.91 (m, 2H), 2.60-2.74 (m, 2H), 1.89-2.24 (m, 6H), 1.55-1.74 (m, 8H), 1.11-1.20 (m, 1H).

[0425] The chemical structural formula is shown as formula IV-51:

[0426] Example 52:

[0427] This example gives a preparation method of imidazo[1,2-a]pyrimidine sophoridine derivative, which is basically the same as example 28, the difference is that in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is 2,5-difluoro-α-bromoacetophenone.

[0428] In this example, the target compound IV-52 prepared in step three is subjected to physical and chemical property and characterization analysis, and the results are as follows:

[0429] Physical and chemical properties: yellow solid, melting point 133-135°C, yield 48%.

[0430] Infrared spectrum: IR cm -1 (KBr): 3708, 2934, 2362, 1660, 1484, 760.

[0431] Nuclear magnetic resonance hydrogen spectrum: 1H NMR (500 MHz, CDC13) δ: 8.13-8.17 (m, 1H), 7.65 (s, 1H), 7.54 (d, J = 4.0 Hz, 1H), 6.99-7.05 (m, 1H), 6.84-6.88 (m, 1H), 3.72-3.76 (m, 1H), 3.54-3.56 (m, 2H), 2.81-2.92 (m, 2H), 2.60-2.70 (m, 2H), 2.07-2.21 (m, 5H), 1.89-1.92 (m, 3H), 1.56-1.75 (m, 6H), 1.12-1.19 (m, 1H).

[0432] The chemical structural formula of the compound is shown as formula IV-52.

[0433] Example 53

[0434] This example gives a preparation method of an imidazo[1,2-a]pyrimidine sophoridine derivative. The method is basically the same as that in Example 28, except that in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is 3,4-dichloro-α-bromoacetophenone.

[0435] In this example, the physical and chemical properties and characterization analysis of the target compound IV-53 prepared in step three were carried out, and the results are as follows:

[0436] Physical and chemical properties: yellow solid, melting point 146-148°C, yield 45%.

[0437] Infrared spectrum: IR cm -1 (KBr): 3694, 2924, 1655, 1459, 1340, 725.

[0438] Nuclear magnetic resonance hydrogen spectrum: 1 H NMR (500 MHz, CDC13) δ: 8.13-8.17 (m, 1H), 7.65 (s, 1H), 7.54 (d, J = 4.0 Hz, 1H), 6.99-7.05 (m, 1H), 6.84-6.88 (m, 1H), 3.72-3.76 (m, 1H), 3.54-3.56 (m, 2H), 2.81-2.92 (m, 2H), 2.60-2.70 (m, 2H), 2.07-2.21 (m, 5H), 1.89-1.92 (m, 3H), 1.56-1.75 (m, 6H), 1.12-1.19 (m, 1H).

[0439] The chemical structural formula of the compound is shown as formula IV-53. The chemical structural formula of the compound is shown as formula IV-53.

[0440] Example 54

[0441] This example gives a preparation method of imidazo[1,2-a]pyrimidine sophoridine derivative, which is basically the same as that of Example 28, the difference is that in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is p-trifluoromethoxy-α-bromoacetophenone.

[0442] In this example, the target compound IV-54 prepared in step three was subjected to physical and chemical property and characterization analysis, and the results were as follows:

[0443] Physical and chemical properties: yellow solid, melting point 127-129°C, yield 40%.

[0444] Infrared spectrum: IR cm -1 (KBr): 3675, 2930, 1659, 1476, 1347, 1260, 851.

[0445] Nuclear magnetic resonance hydrogen spectrum: 1 H NMR (500 MHz, CDCI3) δ: 7.96 (d, J = 9.0 Hz, 2H), 7.64 (s, 1H), 7.32 (s, 1H), 7.21 (d, J = 8.0 Hz, 2H), 3.74 (dd, J = 5.0 Hz, 13.5 Hz, 1H), 3.52-3.56 (m, 2H), 2.81-2.91 (m, 2H), 2.59-2.70 (m, 2H), 2.07-2.21 (m, 5H), 1.89-1.94 (m, 3H), 1.55-1.77 (m, 6H), 1.11-1.19 (m, 1H).

[0446] The chemical structural formula is shown as formula IV-54:

[0447] Example 55

[0448] This example gives a preparation method of imidazo[1,2-a]pyrimidine sophoridine derivative, which is basically the same as that of Example 28, the difference is that in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is α-bromo-1-naphthylacetophenone.

[0449] In this example, the target compound IV-55 prepared in step three was subjected to physical and chemical property and characterization analysis, and the results were as follows:

[0450] Physical and chemical properties: yellow solid, melting point 155-156°C, yield 68%.

[0451] Infrared spectrum: IR cm-1 (KBr): 3693, 2923, 1655, 1476, 1339, 777.

[0452] H NMR (400 MHz, CDC13) δ: 8.77-8.78 (m, 1H), 7.79-7.91 (m, 3H), 7.72 (s, 1H), 7.48-7.52 (m, 3H), 7.34 (s, 1H), 3.72-3.75 (m, 1H), 3.55-3.60 (m, 2H), 2.81-2.91 (m, 2H), 2.67 (s, 2H), 2.09-2.22 (m, 4H), 1.57-1.92 (m, 10H), 1.15-1.17 (m, 1H).

[0453] The chemical structural formula is shown as formula IV-55:

[0454] Example 56

[0455] This example gives a preparation method of imidazo[1,2-a]pyrimidine sophoridine derivative, which is basically the same as example 28, the difference is that in step three, the α-bromo aromatic ketone is different. In this example, the α-bromo aromatic ketone is α-bromo-2-naphthaldehyde.

[0456] In this example, the target compound IV-56 prepared in step three is subjected to physical and chemical property and characterization analysis, and the results are as follows:

[0457] Physical and chemical properties: yellow solid, melting point 150-152°C, yield 38%.

[0458] Infrared spectrum: IR cm -1 (KBr): 3679, 2924, 1652, 1473, 1337, 752.

[0459] H NMR (400 MHz, CDC13) δ: 8.77-8.78 (m, 1H), 7.79-7.91 (m, 3H), 7.72 (s, 1H), 7.48-7.52 (m, 3H), 7.34 (s, 1H), 3.72-3.75 (m, 1H), 3.55-3.60 (m, 2H), 2.81-2.91 (m, 2H), 2.67 (s, 2H), 2.09-2.22 (m, 4H), 1.57-1.92 (m, 10H), 1.15-1.17 (m, 1H).

[0460] H NMR (400 MHz, CDC13) δ: 8.54 (s, 1H), 7.94-7.96 (m, 1H), 7.85-7.87 (m, 1H), 7.79-7.82 (m, 2H), 7.63 (s, 1H), 7.41-7.45 (m, 3H), 3.72-3.76 (m, 1H), 3.52-3.58 (m, 2H), 2.78-2.91 (m, 2H), 2.60-2.63 (m, 2H), 2.05-2.22 (m, 4H), 1.71-1.92 (m, 5H), 1.55-1.63 (m, 5H), 1.14-1.19 (m, 1H).​

[0460] The chemical structural formula is shown as formula IV-56:

[0461] Example 57:

[0462] This example shows the application of imidazo[1,2-a]pyrimidine matrine / sophoridine derivatives as acaricides. Tetranychus cinnabarinus Bois. is used as the test insect (passaged and fed in the laboratory of the inventor). The imidazo[1,2-a]pyrimidine matrine / sophoridine derivatives prepared in Examples 1-56, matrine, sophoridine, intermediate II-1, intermediate II-2, intermediate III-1, and intermediate III-2 are used as the experimental group. 98.32% spirodiclofen technical material (provided by Shaanxi Meibang Pesticide Co., Ltd.) is used as the positive control group.

[0463] This application uses the glass dipping method recommended by FAO, and the specific process is as follows:

[0464] ① 0.1‰ Tween 80 stock solution preparation: weigh 25 mg of Tween 80 into 5 mL of acetone solution, and dilute with distilled water to 250 mL for use.

[0465] ② Preparation of primary screening solution: weigh 3.0 mg of test compound, dissolve in 120 microliters of acetone (2% of the target volume), and then dilute with the prepared 0.1‰ Tween 80 to 6.0 mL to prepare a 500 mg / L solution for primary screening.

[0466] ③ Preparation of test mites: attach a 1 cm wide double-sided tape to one end of a glass slide, and use a No. 0 brush to select healthy and active Tetranychus cinnabarinus female adult mites of consistent age, carefully and neatly sticking their backs to the double-sided tape on the glass slide, with 30-40 mites per slide, arranged in two rows. Place the slide with test mites on an iron plate lined with a wet sponge, and place the iron plate in a light incubator at 26±1°C, 60%-80% relative humidity, and light L:D=14h:10h. After 4 hours, check under a stereomicroscope and remove dead and inactive individuals, and record the number of live mites on each slide.

[0467] ④ Dipping: dip the end of the glass slide with mites in the test solution for 5 seconds, then remove the excess solution with a small filter paper strip (be careful not to touch the mite body), and place it back in the iron plate in the same incubation conditions. One slide is one treatment, with 3 replicates per treatment, and 0.1‰ Tween 80 solution is used as the blank control.

[0468] (5) Result statistics: the slide was taken out after 24 hours of immersion treatment, and the results were checked under a stereomicroscope. When checking, the mite body was gently touched with a brush tip, and those with immobile chelicerae were considered dead, and the number of dead individuals was recorded. The observation and recording were continuously performed for 72 hours. The mortality rate (%) and the corrected mortality rate (%) of the test mites for 48 hours and 72 hours were calculated according to the following formula: The final experimental results are shown in Table 1.

[0469] Table 1, acaricidal activity of imidazo[1,2-a]pyrimidine matrine / sophoridine derivatives, matrine, sophoridine, intermediate II-1, intermediate II-2, intermediate III-1, and intermediate III-2

[0470]

[0471]

[0472] As can be seen from Table 1, the 72h acaricidal activity of some of the above imidazo[1,2-a]pyrimidine matrine / sophoridine derivatives is significantly improved compared with matrine and sophoridine, and the 72h acaricidal activity of some of the derivatives is comparable to that of spirodiclofen, so they are expected to be used for preparing plant-derived acaricides with high efficiency, environmental protection, and low toxicity.

Claims

1. An imidazo[1,2-a]pyrimidine matrine / sophoridine derivative, characterized in that: The chemical structural formula is shown as formula IV: Formula IV; In the formula: R 1 is an α-hydrogen or a β-hydrogen; R 1 When R 1 When R The R 2 Selected from phenyl, o-methylphenyl, m-methylphenyl, p-methylphenyl, o-methoxyphenyl, m-methoxyphenyl, p-methoxyphenyl, p-phenoxyphenyl, o-fluorophenyl, m-fluorophenyl, p-fluorophenyl, o-chlorophenyl, m-chlorophenyl, p-chlorophenyl, o-bromophenyl, m-bromophenyl, p-bromophenyl, o-trifluoromethylphenyl, m-trifluoromethylphenyl, p-trifluoromethylphenyl, o-nitrophenyl, m-nitrophenyl, p-nitrophenyl, 2,5-difluorophenyl, 3,4-dichlorophenyl, p-trifluoromethoxyphenyl, 1-naphthyl, 2-naphthyl.

2. A process for the preparation of an imidazo[1,2-a]pyrimidine matrine / sophoridine derivative according to claim 1, characterized in that, The method comprises the following steps: The chemical structural formula of the matrine and sophoridine is shown as formula I-1 and formula I-2 respectively: Formula I-1; Formula I-2; The chemical structural formula of the intermediate II-1 or II-2 is shown as formula II-1 or II-2 respectively: Formula II-1; Formula II-2; The chemical structural formula of the intermediate III-1 or III-2 is shown as formula III-1 or III-2 respectively: Formula III-1; Formula III-2.

3. The method of claim 2, wherein the imidazo[1,2-a]pyrimidine matrine / oxymatrine derivative is prepared by the reaction of the compound of formula (II) with the compound of formula (III) in the presence of a base. The α-bromo aromatic ketone is selected from α-bromoacetophenone, o-methyl-α-bromoacetophenone, m-methyl-α-bromoacetophenone, p-methyl-α-bromoacetophenone, o-methoxy-α-bromoacetophenone, m-methoxy-α-bromoacetophenone, p-methoxy-α-bromoacetophenone, p-phenoxy-α-bromoacetophenone, o-fluoro-α-bromoacetophenone, m-fluoro-α-bromoacetophenone, p-fluoro-α-bromoacetophenone, o-chloro-α-bromoacetophenone, m-chloro-α-bromoacetophenone, p-chloro-α-bromoacetophenone, o-bromo-α-bromoacetophenone, m-bromo-α-bromoacetophenone, p-bromo-α-bromoacetophenone, o-trifluoromethyl-α-bromoacetophenone, m-trifluoromethyl-α-bromoacetophenone, p-trifluoromethyl-α-bromoacetophenone, o-nitro-α-bromoacetophenone, m-nitro-α-bromoacetophenone, p-nitro-α-bromoacetophenone, 2,5-difluoro-α-bromoacetophenone, 3,4-dichloro-α-bromoacetophenone, p-trifluoromethoxy-α-bromoacetophenone, α-bromo-1-naphthylacetophenone, α-bromo-2-naphthylacetophenone.

4. The method of claim 2, wherein the imidazo[1,2-a]pyrimidine matrine / sophoridine derivative is prepared by the reaction of the compound of formula (II) with the compound of formula (III) in the presence of a base. The method specifically comprises the following steps: Step one: slowly drop phosphorus oxychloride into the solvent at -5-5 ℃, then drop the solution containing matrine or sophoridine into the above system, gradually heat to 15-35 ℃, react for 4-6 h, remove the solvent in the system under reduced pressure, add ice water and adjust the pH value of the system, then heat to 50-70 ℃ and stir for 1-7 h, filter the product, wash the filter cake and purify by column chromatography to obtain the intermediate II-1 or II-2; Step two: add potassium carbonate and guanidine hydrochloride into the solution containing the intermediate II-1 or II-2, heat to reflux for 8-14 h, cool to 15-35 ℃, remove the solvent under reduced pressure, then extract, combine the organic phase, dry, concentrate and purify by column chromatography to obtain the intermediate III-1 or III-2; Step three: slowly add α-brominated aromatic ketone into the solution containing intermediate III-1 or III-2, stir at 15-35℃ for 5-17 h, after TLC tracking detects that the reaction is completed, add NaCl solution into the reaction system, then extract, combine the organic phase, dry, concentrate and separate and purify by TLC to prepare imidazo[1,2-a]pyrimidine matrine or sophoridine derivatives.

5. The method of claim 4, wherein the imidazo[1,2-a]pyrimidine matrine / oxymatrine derivative is prepared by the reaction of the compound of formula (II) with the compound of formula (III) in the presence of a base. In step one, the solvent consists of N,N-dimethylformamide and dichloromethane, and the volume ratio of N,N-dimethylformamide and dichloromethane is 3:

25.

6. The method for preparing imidazo[1,2-a]pyrimidinematrine / sophoridine derivatives according to claim 4, characterized in that: In step one, the solution containing matrine or sophoridine uses dichloromethane as the solvent.

7. The method of claim 4, wherein the imidazo[1,2-a]pyrimidine matrine / oxymatrine derivative is prepared by the reaction of the compound of formula (II) with the compound of formula (III) in the presence of a base. In step two, the solution containing intermediate II-1 or II-2 uses n-butanol as the solvent.

8. The method for preparing imidazo[1,2-a]pyrimidinematrine / sophoridine derivatives according to claim 4, wherein: In step three, the solution containing intermediate III-1 or III-2 uses N,N-dimethylformamide as the solvent.

9. Use of the imidazo[1,2-a]pyrimidine matrine / sophoridine derivative of claim 1 for preparing acaricides.

Images