Synthetic method of pyrazolo [1, 5-a] pyrimidine-7-amine compound

Abstract

The invention discloses a synthesis method of a pyrazolo [1, 5-a] pyrimidine-7-amine compound, which comprises the following steps: adding 5-substituent-7-(trifluoromethyl) pyrazolo [1, 5-a] pyrimidine as shown in a formula (II) and substituted amine as shown in a formula (III) into a solvent, adding an inorganic base catalyst into the solvent, reacting at a set temperature, and after the reaction is finished, separating and purifying to obtain the pyrazolo [1, 5-a] pyrimidine-7-amine compound. And further performing post-treatment to obtain the pyrazolo [1, 5-a] pyrimidine-7-amine compound. The invention provides a new method for synthesizing the pyrazolo [1, 5-a] pyrimidine-7-amine compound, and the method is characterized in that 5-substituent-7-(trifluoromethyl) pyrazolo [1, 5-a] pyrimidine and substituted amine are used as raw materials to synthesize the pyrazolo [1, 5-a] pyrimidine-7-amine compound in one step in an organic solvent under the action of an inorganic base catalyst. The novel method is novel in reaction, high in synthesis yield, simple to operate and suitable for industrial production. The pyrazolo [1, 5-a] pyrimidine-7-amine compound provided by the invention has good anticancer activity, and has a very good application prospect in the fields of medicines, pesticide chemistry and the like.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and specifically relates to a method for synthesizing a pyrazolo[1,5-a]pyrimidine-7-amine compound. Background Art

[0002] Pyrazolo[1,5-a]pyrimidine compounds are fused heterocyclic compounds composed of a pyrazole ring and a pyrimidine ring, and their structure is similar to purine. A large number of studies have shown that pyrazolo[1,5-a]pyrimidine compounds have good biological activities, such as anti-anxiety drugs, antihypertensive drugs, anti-epileptic drugs, analgesics, muscle relaxants, can treat mammalian neurological diseases, can be used as adrenocorticotropic hormone receptor antibodies and cyclooxygenase-2 inhibitors, and as estrogen receptor ligands. In addition, many pyrazolo[1,5-a]pyrimidine compounds also exhibit herbicidal, insecticidal, plant growth regulating functions. Therefore, pyrazolo[1,5-a]pyrimidine compounds have become a research hotspot in pharmaceutical and pesticide chemistry.

[0003] As an important derivative of pyrazolo[1,5-a]pyrimidine, pyrazolo[1,5-a]pyrimidine-7-amines also have good biological activity. A large number of studies have shown that these compounds can be used as inhibitors of cyclin-dependent kinases (CDKs), mitogen-activated protein kinases (MAPK / ERK), glycogen synthase kinase 3β (GSK3beta), etc., and play a pivotal role in the field of anti-tumor. Therefore, the development of simple, efficient and convenient methods to synthesize pyrazolo[1,5-a]pyrimidine-7-amine compounds is of great research value and significance.

[0004] The currently reported methods for synthesizing pyrazolo[1,5-a]pyrimidine-7-amines mainly use 7-hydroxy-pyrazolo[1,5-a]pyrimidine compounds as raw materials, carry out chlorination reaction under phosphorus oxychloride conditions to obtain 7-chloro-pyrazolo[1,5-a]pyrimidine compounds, and then the 7-chloro-pyrazolo[1,5-a]pyrimidine compounds react with substituted amines under alkaline conditions to obtain pyrazolo[1,5-a]pyrimidine-7-amine compounds. For example, the following synthesis route is disclosed in the publication number CN101120000A "Pyrazolopyrimidine":

[0005] From the above synthesis method, we can see that this method has two-step reactions, low comprehensive yield, and uses highly toxic substances such as POCl3, which is not suitable for large-scale industrial production. Therefore, developing a simple, efficient and fast method to synthesize pyrazolo[1,5-a]pyrimidine-7-amine derivatives is of great significance to promote the development and utilization of such compounds. Summary of the invention

[0006] In view of the defects of the prior art, the purpose of the present invention is to provide a method for synthesizing pyrazolo[1,5-a]pyrimidine-7-amine compounds. The method of the present invention uses 5-substituted-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine and substituted amine as raw materials, and uses an inorganic base as a catalyst to prepare pyrazolo[1,5-a]pyrimidine-7-amine compounds. In the method, the reaction conditions are mild, the operation is simple, the yield is high, and the pyrazolo[1,5-a]pyrimidine-7-amine compounds can be synthesized in one step.

[0007] The present application provides a method for synthesizing pyrazolo[1,5-a]pyrimidine-7-amine compounds, using the following technical scheme: A method for synthesizing a pyrazolo[1,5-a]pyrimidine-7-amine compound comprises the following steps: The 5-R1-substituted-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine of formula (II) and the substituted amine of formula (III) are added to a solvent, an inorganic base catalyst is added thereto, and the reaction is carried out at a set temperature. After the reaction is completed, further post-treatment is carried out to obtain a pyrazolo[1,5-a]pyrimidine-7-amine compound of formula (I); The specific synthetic route is as follows:

[0008] Wherein: R1 is selected from: substituted or unsubstituted C6~C10 aryl, substituted or unsubstituted C5~C10 heteroaryl; R2 is selected from: H, substituted aryl-2-ylmethyl; R3 is selected from: substituted or unsubstituted C1~C6 alkyl, substituted or unsubstituted C3~C7 cycloalkyl.

[0009] Preferably, R1 is selected from: a substituted or unsubstituted benzene ring, a naphthalene ring, furan, thiophene, pyridine, oxazole, isoxazole, thiazole, isothiophene, pyrrole, imidazole, pyrazole, pyrimidine, pyrazine, pyridazine; wherein the substitution refers to substitution by one or more groups selected from the following group, and the substituents include but are not limited to: halogen, hydroxyl, amino, carboxyl, cyano, nitro, methanesulfonyl, sulfamoyl, trifluoromethyl, substituted or unsubstituted C1~C6 alkyl, substituted or unsubstituted C3~C7 cycloalkyl, substituted or unsubstituted C1~C6 alkoxy, (C1~C4 alkyl)NH-, di(C1~C4 alkyl)amino; R2 is selected from the group consisting of: H, substituted benzyl, substituted thien-2-ylmethyl, substituted furan-2-ylmethyl.

[0010] Preferably, the molar ratio of the 5-substituted-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine of formula (II) to the substituted amine of formula (III) is 1:1-1:3, preferably 1:2.

[0011] Preferably, the molar ratio of 5-substituted-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine represented by formula (II) to the inorganic base is 1:0.5-1:8.

[0012] Preferably, the inorganic base is selected from one or more of K2CO3, Cs2CO3, NaH, CaH2, NaOH, and KOH; further preferably, it is a combination of Cs2CO3 and CaH2, wherein the molar ratio of Cs2CO3 to CaH2 is 1:0.5-1:3.

[0013] Preferably, the solvent is selected from dimethyl sulfoxide, N,N -dimethylformamide, N,N -Dimethylacetamide, N -Methyl pyrrolidone, 1,4-dioxane, toluene or one or more mixtures; more preferably N,N -Dimethylformamide.

[0014] Preferably, the reaction temperature is 80-130°C, and the reaction time is 6-10h; further preferably, the reaction temperature is 120°C, and the reaction time is 8h.

[0015] Preferably, the post-treatment specifically includes extraction, drying, vacuum distillation, elution, and column chromatography separation steps; further preferably, the elution uses eluents of water and acetonitrile in a volume ratio of (1-2):(1-3).

[0016] Preferably, the method for preparing the 5-R1-substituted-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine represented by formula (II) comprises the following steps: Dissolve 4,4,4-trifluoro-1-substituted butane-1,3-dione and 3-aminopyrazole in a solvent, raise the temperature to the reaction temperature, and after the reaction is completed, pour into water, precipitate solid, filter, and slurry with ethanol to obtain 5-substituted-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine shown in formula (II); The synthetic route is as follows: .

[0017] Preferably, the solvent is acetic acid, the molar ratio of 4,4,4-trifluoro-1-substituted butane-1,3-dione represented by formula (IV) and 3-aminopyrazole is 1:1-1:1.3; the reaction temperature is 90-110°C, and the reaction time is 1.5-3h.

[0018] The pyrazolo[1,5-a]pyrimidine-7-amine compound represented by formula (I) prepared according to the above synthesis method is used in the field of medicine or pesticide.

[0019] Beneficial effects of the present invention: (1) The present invention provides a new method for synthesizing pyrazolo[1,5-a]pyrimidine-7-amine compounds, which uses 5-substituted-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine and substituted amine as raw materials, in an organic solvent, under the action of an inorganic base catalyst, to synthesize pyrazolo[1,5-a]pyrimidine-7-amine compounds in one step; the new method has novel reaction, high synthesis yield, simple operation, and is suitable for industrial production.

[0020] (2) The pyrazolo[1,5-a]pyrimidine-7-amine compounds provided in the present application have good anticancer activity and have very good application prospects in the fields of medicine and pesticide chemistry. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 This is the NMR spectrum of the product I-1 in Example 1.

[0022] Figure 2 This is the NMR spectrum of product I-2 in Example 2.

[0023] Figure 3 This is the NMR spectrum of product I-3 in Example 3.

[0024] Figure 4 This is the NMR spectrum of product I-4 in Example 4.

[0025] Figure 5 This is the NMR spectrum of product I-5 in Example 5.

[0026] Figure 6 This is the NMR spectrum of product I-6 in Example 6.

[0027] Figure 7 This is the NMR spectrum of product I-10 in Example 10.

[0028] Figure 8 This is the NMR spectrum of product I-15 in Example 15.

[0029] Fig. 9 This is the NMR spectrum of product I-22 in Example 22.

[0030] Fig.10 This is the NMR spectrum of product I-25 in Example 25. DETAILED DESCRIPTION

[0031] The following is a detailed description of the specific embodiments of the present invention, but it should be understood that the protection scope of the present invention is not limited by the specific embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work belong to the protection scope of the present invention. The experimental methods described in the embodiments of the present invention are conventional methods unless otherwise specified.

[0032] The following test methods and detection methods, unless otherwise specified, are conventional methods; the following reagents and raw materials, unless otherwise specified, are commercially available. Preparation Example 1

[0033] The synthetic route of this preparation example is as follows:

[0034] The specific steps include: 4,4,4-trifluoro-1-phenylbutane-1,3-dione (10 mmol, 1.86 g) and 3-aminopyrazole (11 mmol, 0.91 g) shown in formula (Ⅳ-1) were dissolved in 20 mL of acetic acid, heated to 100°C for reaction for 2 h. After the reaction was completed, the mixture was poured into water, the solid was precipitated, filtered, and slurried with ethanol to obtain 5-(phenyl)-7-(trifluoromethyl)pyrazole[1,5-a]pyrimidine shown in formula (Ⅱ-1). Example 1

[0035] The synthetic route of the present embodiment is as follows:

[0036] N -Synthesis of cyclohexyl-5-phenylpyrazolo[1,5-a]pyrimidin-7-amine: 5-(Phenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (0.20 g, 0.76 mmol) of formula (II-1) prepared in Preparation Example 1, cyclohexylamine (0.15 g, 1.52 mmol), Cs2CO3 (0.49 g, 1.52 mmol), CaH2 (0.13 g, 3.04 mmol) and DMF (4 ml) were placed in a 10 ml single-necked bottle and reacted at 120°C for 8 h. The system was poured into 20 ml of water and extracted with ethyl acetate. The organic phases were combined, dried, filtered, and the solvent was evaporated under reduced pressure. The target compound N-cyclohexyl-5-phenylpyrazolo[1,5-a]pyrimidine-7-amine was obtained as a beige solid of formula (I-1) in a yield of 89%.

[0037] The target compound prepared in this example was characterized, and its NMR spectrum was as follows: Figure 1 The specific characterization data are as follows: Characterization data: 1 H NMR (400 MHz, DMSO- d 6) δ 8.21 – 8.18 (m, 2H), 8.09 (d, J = 2.4 Hz, 1H), 7.56 – 7.49 (m, 4H), 6.75 (s, 1H), 6.47 (d, J = 2.4 Hz, 1H),3.87 – 3.85 (m, 1H), 1.98 – 1.95 (m, 2H), 1.78 – 1.74 (m, 2H), 1.67 – 1.63(m, 1H), 1.59 – 1.40 (m, 4H), 1.21 – 1.15 (m, 1H). 13 C NMR (101 MHz, DMSO- d 6) δ 156.42, 149.38, 146.56, 144.10, 138.84,130.04, 128.95, 127.63, 95.34, 82.11, 50.66, 32.48, 25.52, 25.13. LC-MS: [M+H]+=293.2.

[0038] Preparation Example 2 The synthetic route of this preparation example is as follows:

[0039] The specific steps include: 4,4,4-trifluoro-1-(furan)butane-1,3-dione (10 mmol, 1.76 g) and 3-aminopyrazole (12 mmol, 0.99 g) shown in formula (Ⅳ-2) were dissolved in 20 mL of acetic acid, heated to 95°C and reacted for 2.5 hours. After the reaction was completed, the mixture was poured into water, the solid was precipitated, filtered, and slurried with ethanol to obtain 5-(furan-2-yl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine shown in formula (Ⅱ-2). Example 2

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

[0041] Synthesis of N-cyclohexyl-5-(furan-2-yl)pyrazolo[1,5-a]pyrimidin-7-amine: 5-(furan-2-yl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (0.20 g, 0.79 mmol) of formula (II-2) prepared in Preparation Example 2, cyclohexylamine (0.15 g, 1.58 mmol), Cs2CO3 (0.51 g, 1.58 mmol), CaH2 (0.13 g, 3 .16mmol), DMF (4ml), placed in a 10ml single-mouth bottle, reacted at 120℃ for 8h, poured into 20ml of water, extracted with ethyl acetate, combined the organic phases, dried, filtered, and the solvent was evaporated under reduced pressure. After separation by column chromatography (water / acetonitrile = 2:3), a beige solid was obtained, which was the target compound N-cyclohexyl-5-(furan-2-yl)pyrazolo[1,5-a]pyrimidin-7-amine represented by formula (Ⅰ-2), with a yield of 94%.

[0042] The target compound prepared in this example was characterized, and its NMR spectrum was as follows: Figure 2 The specific characterization data are as follows: Characterization data: 1 H NMR (400 MHz, DMSO- d 6) δ 8.07 (d, J = 2.0 Hz, 1H), 7.89(s, 1H), 7.63 (d, J = 8.8 Hz, 1H), 7.24 (d, J = 3.6 Hz, 1H), 6.69 (dd, J =3.2, 1.6 Hz, 1H), 6.52 (s, 1H), 6.42 (d, J = 2.2 Hz, 1H), 3.71 – 3.69 (m,1H), 1.96 – 1.93 (m, 2H), 1.78 – 1.74 (m, 2H), 1.65 – 1.62 (m, 1H), 1.55 –1.41 (m, 4H), 1.17 – 1.14 (m, 1H). 13 C NMR (101 MHz, DMSO- d 6) δ 153.14, 149.22, 148.34, 146.44, 145.01,144.17, 112.88, 110.82, 95.08, 80.30, 51.03, 32.37, 25.50, 25.11. LC-MS: [M+H]+=283.2.

[0043] Preparation Example 3 The synthetic route of this preparation example is as follows:

[0044] The specific steps include: 4,4,4-trifluoro-1-(thiophene)butane-1,3-dione (10 mmol, 1.92 g) and 3-aminopyrazole (11 mmol, 0.91 g) shown in formula (Ⅳ-3) were dissolved in 20 mL of acetic acid, heated to 110°C and reacted for 1.5 hours. After the reaction was completed, the mixture was poured into water, the solid was precipitated, filtered, and slurried with ethanol to obtain 5-(thiophene-2-yl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine shown in formula (Ⅱ-3). Example 3

[0045] The synthetic route of the present embodiment is as follows:

[0046] Synthesis of N-cyclohexyl-5-(thiophen-2-yl)pyrazolo[1,5-a]pyrimidin-7-amine: 5-(thiophen-2-yl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (0.20 g, 0.74 mmol) of formula (II-3) prepared in Preparation Example 3, cyclohexylamine (0.14 g, 1.48 mmol), Cs2CO3 (0.48 g, 1.48 mmol), CaH2 (0.13 g, 2.96 mmol), DMF (4 ml) were placed in a 10 ml single-necked bottle, reacted at 120 °C for 8 h, poured into 20 ml of water, extracted with ethyl acetate, combined the organic phases, dried, filtered, and the solvent was evaporated under reduced pressure. After separation by column chromatography (water / acetonitrile = 2:3), a beige solid was obtained, which is the target compound of formula (I-3). N -cyclohexyl-5-(thiophen-2-yl)pyrazolo[1,5-a]pyrimidin-7-amine, yield 95%.

[0047] The target compound prepared in this example was characterized, and its NMR spectrum was as follows: Figure 3 The specific characterization data are as follows: Characterization data: 1 H NMR (400 MHz, DMSO- d 6) δ 8.06 – 8.03 (m, 2H), 7.69 (dd, J = 4.8, 1.0 Hz, 1H), 7.55 (d, J = 9.2 Hz, 1H), 7.19 (dd, J= 4.8, 3.6 Hz, 1H), 6.76 (s, 1H), 6.41 (d, J = 2.4 Hz, 1H), 3.88 – 3.74 (m, 1H), 2.00 – 1.91 (m,2H), 1.81 – 1.74 (m, 2H), 1.68 – 1.63 (m, 1H), 1.54 – 1.42 (m, 4H), 1.07 –0.98 (m, 1H). 13 C NMR (101 MHz, DMSO- d 6) δ 157.06, 151.95, 148.95, 146.35, 144.89,144.04, 129.75, 128.58, 127.68, 94.97, 80.73, 50.74, 32.46, 25.50, 25.15. LC-MS: [M+H]+=299.1.

[0048] Preparation Example 4 The synthetic route of this preparation example is as follows:

[0049] The specific steps include: 4,4,4-trifluoro-1-(pyridine)butane-1,3-dione (10 mmol, 1.87 g) and 3-aminopyrazole (11 mmol, 0.91 g) shown in formula (Ⅳ-4) were dissolved in 20 mL of acetic acid, heated to 100°C for reaction for 2 hours. After the reaction was completed, the mixture was poured into water, the solid was precipitated, filtered, and slurried with ethanol to obtain 5-(pyridin-2-yl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine shown in formula (Ⅱ-4). Example 4

[0050] The synthetic route of the present embodiment is as follows:

[0051] N -Synthesis of cyclohexyl-5-(pyridin-2-yl)pyrazolo[1,5-a]pyrimidin-7-amine: 5-(Pyridin-2-yl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (0.20 g, 0.75 mmol) of formula (II-4) prepared in Preparation Example 4, cyclohexylamine (0.15 g, 1.50 mmol), Cs2CO3 (0.49 g, 1.50 mmol), CaH2 (0.13 g, 3.00 mmol) and DMF (4 ml) were placed in a 10 ml single-necked bottle and reacted at 120 °C for 8 h. The system was poured into 20 ml of water and extracted with ethyl acetate. The organic phases were combined, dried, filtered, and the solvent was evaporated under reduced pressure. The mixture was separated by column chromatography (water / acetonitrile = 2:3) to obtain a beige solid, which was the target compound N-cyclohexyl-5-(pyridin-2-yl)pyrazolo[1,5-a]pyrimidin-7-amine of formula (I-4) in a yield of 93%.

[0052] The target compound prepared in this example was characterized, and its NMR spectrum was as follows: Figure 4 The specific characterization data are as follows: Characterization data: 1 H NMR (400 MHz, DMSO- d 6) δ 8.73 (d, J = 4.4 Hz, 1H), 8.44(d, J = 8.0 Hz, 1H), 8.14 (d, J = 2.0 Hz, 1H), 7.98 – 7.94 (m, 1H), 7.71 (d, J = 8.8 Hz, 1H), 7.50 (dd, J = 7.2, 5.2 Hz, 1H), 7.18 (s, 1H), 6.55 (d, J =2.4 Hz, 1H), 3.70 – 3.68 (m, 1H), 1.99 – 1.97 (m, 2H), 1.79 – 1.76 (m, 2H), 1.67 – 1.62 (m, 1H), 1.59 – 1.52 (m, 2H), 1.48 – 1.42 (m, 2H), 1.22 – 1.16(m, 1H). 13 C NMR (101 MHz, DMSO- d6) δ 155.36, 155.15, 149.52, 149.25, 146.63,144.33, 137.66, 125.16, 121.41, 95.82, 81.60, 51.32, 32.37, 25.52, 25.15. LC-MS: [M+H]+=294.2.

[0053] Preparation Example 5 The synthetic route of this preparation example is as follows:

[0054] The specific steps include: 4,4,4-trifluoro-1-(4-(methylthio)phenyl)butane-1,3-dione (10mmol, 2.33g) and 3-aminopyrazole (13mmol, 1.08g) shown in formula (IV-5) were dissolved in 20mL of acetic acid, heated to 100°C for reaction for 2h. After the reaction was completed, the mixture was poured into water, the solid was precipitated, filtered, and slurried with ethanol to obtain 5-(4-(methylthio)phenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine shown in formula (II-5). Example 5

[0055] The synthetic route of the present embodiment is as follows:

[0056] N Synthesis of cyclohexyl-5-(4-(methylthio)phenyl)pyrazolo[1,5-a]pyrimidin-7-amine: 5-(4-(methylthio)phenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (0.20 g, 0.65 mmol) of formula (II-5) prepared in Preparation Example 5, cyclohexylamine (0.13 g, 1.30 mmol), Cs2CO3 (0.42 g, 1.30 mmol), CaH2 (0.11 g, 2.60 mmol), DMF (4 ml) were placed in a 10 ml single-necked bottle, reacted at 120 °C for 8 h, poured into 20 ml of water, extracted with ethyl acetate, combined the organic phases, dried, filtered, and the solvent was evaporated under reduced pressure. After separation by column chromatography (water / acetonitrile = 2:3), a beige solid was obtained, which was the target compound of formula (I-5). N -cyclohexyl-5-(4-(methylthio)phenyl)pyrazolo[1,5-a]pyrimidin-7-amine, yield 88%.

[0057] The target compound prepared in this example was characterized, and its NMR spectrum was as follows: Figure 5 The specific characterization data are as follows: Characterization data: 1 H NMR (400 MHz, DMSO- d 6) δ 8.16 (d, J = 8.4 Hz, 2H), 8.07(d, J = 2.0 Hz, 1H), 7.51 (d, J = 9.2 Hz, 1H), 7.36 (d, J = 8.4 Hz, 2H), 6.73(s, 1H), 6.45 (d, J = 2.4 Hz, 1H), 3.87 – 3.84 (m, 1H), 2.54 (s, 3H), 1.97 –1.95 (m, 2H), 1.78 – 1.75 (m, 2H), 1.67 – 1.64 (m, 1H), 1.58 – 1.44 (m, 4H),1.22 – 1.15 (m, 1H). 13 C NMR (101 MHz, DMSO- d 6) δ 155.80, 149.35, 146.52, 144.07, 140.77,135.14, 128.04, 125.86, 95.21, 81.66, 50.63, 32.48, 25.52, 25.13, 14.82. LC-MS: [M+H]+=339.1.

[0058] Preparation Example 6 The synthetic route of this preparation example is as follows:

[0059] The specific steps include: 4,4,4-trifluoro-1-(4-(methylsulfonyl)phenyl)butane-1,3-dione (5mmol, 0.78g) and 3-aminopyrazole (6.2mmol, 0.51g) shown in formula (IV-6) were dissolved in 15mL of acetic acid, heated to 105°C for reaction for 3h. After the reaction was completed, the mixture was poured into water, the solid was precipitated, filtered, and slurried with ethanol to obtain 5-(4-(methylsulfonyl)phenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine shown in formula (II-6).

[0060] Example 6 The synthetic route of the present embodiment is as follows:

[0061] N -Synthesis of cyclohexyl-5-(4-(methylsulfonyl)phenyl)pyrazolo[1,5-a]pyrimidin-7-amine: 5-(4-(methylsulfonyl)phenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (0.20 g, 0.59 mmol) of formula (II-6) prepared in Preparation Example 6, cyclohexylamine (0.12 g, 1.18 mmol), Cs2CO3 (0.38 g, 1.18 mmol), CaH2 (0.99 g, 2.36 mmol), DMF (4 ml) were placed in a 10 ml single-mouth bottle, reacted at 120 ° C for 8 h, poured into 20 ml of water, extracted with ethyl acetate, combined the organic phases, dried, filtered, and the solvent was evaporated under reduced pressure. After separation by column chromatography (water / acetonitrile = 2:3), a beige solid was obtained, which is the target compound of formula (I-6). N -cyclohexyl-5-(4-(methylsulfonyl)phenyl)pyrazolo[1,5-a]pyrimidin-7-amine, yield 78%.

[0062] The target compound prepared in this example was characterized, and its NMR spectrum was as follows: Figure 6 The specific characterization data are as follows: Characterization data: 1 H NMR (400 MHz, DMSO- d 6) δ 8.46 (d, J = 8.4 Hz, 2H), 8.14(d, J = 2.0 Hz, 1H), 8.05 (d, J = 8.4 Hz, 2H), 7.73 (d, J = 9.2 Hz, 1H), 6.87(s, 1H), 6.54 (d, J = 2.0 Hz, 1H), 3.91 – 3.88 (m, 1H), 3.29 (s, 3H), 1.99 –1.95 (m, 2H), 1.79 – 1.76 (m, 2H), 1.68 – 1.65 (m, 1H), 1.58 – 1.45 (m, 4H),1.22 - 1.16 (m, 1H). 13 C NMR (101 MHz, DMSO- d6) δ 154.55, 149.26, 146.73 144.41, 143.56,141.75, 128.51, 127.65, 95.87, 82.70, 50.77, 44.00, 32.43, 25.49, 25.16. LC-MS: [M+H]+=371.2.

[0063] Preparation Example 7 The synthetic route of this preparation example is as follows:

[0064] The specific steps include: 4,4,4-trifluoro-1-(4-methoxyphenyl)butane-1,3-dione (10 mmol, 2.17 g) and 3-aminopyrazole (11 mmol, 0.91 g) shown in formula (Ⅳ-7) were dissolved in 25 mL of acetic acid, heated to 100°C for reaction for 2 hours. After the reaction was completed, the mixture was poured into water, the solid was precipitated, filtered, and slurried with ethanol to obtain 5-(4-methoxyphenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine shown in formula (Ⅱ-7).

[0065] Example 7 The synthetic route of the present embodiment is as follows:

[0066] N -Synthesis of Cyclohexyl-5-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-7-amine 5-(4-methoxyphenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (0.20 g, 0.68 mmol) of formula (II-7) prepared in Preparation Example 7, cyclohexylamine (0.14 g, 1.36 mmol), Cs2CO3 (0.44 g, 1.36 mmol), CaH2 (0.11 g, 2.72 mmol), DMF (4 ml) were placed in a 10 ml single-necked bottle, reacted at 120 ° C for 8 h, poured into 20 ml of water, extracted with ethyl acetate, combined the organic phases, dried, filtered, and the solvent was evaporated under reduced pressure. After separation by column chromatography (water / acetonitrile = 2:3), a beige solid was obtained, which is the target compound of formula (I-7). N -cyclohexyl-5-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-7-amine, yield 89%.

[0067] Characterization data: LC-MS: [M+H]+=395.0.

[0068] Preparation Example 8 The synthetic route of this preparation example is as follows:

[0069] The specific steps include: 4,4,4-trifluoro-1-(6-methoxypyridin-3-yl)butane-1,3-dione (10 mmol, 2.17 g) and 3-aminopyrazole (11 mmol, 0.91 g) shown in formula (Ⅳ-8) were dissolved in 22 mL of acetic acid, heated to 100°C and reacted for 2 hours. After the reaction was completed, the mixture was poured into water, the solid was precipitated, filtered, and slurried with ethanol to obtain 5-(6-methoxypyridin-3-yl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine shown in formula (Ⅱ-8).

[0070] Example 8 The synthetic route of the present embodiment is as follows:

[0071] N -Synthesis of cyclohexyl-5-(6-methoxypyridin-3-yl)pyrazolo[1,5-a]pyrimidin-7-amine: 5-(6-methoxypyridin-3-yl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (0.20 g, 0.68 mmol) of formula (II-8) prepared in Preparation Example 8, cyclohexylamine (0.14 g, 1.36 mmol), Cs2CO3 (0.44 g, 1.36 mmol), CaH2 (0.11 g, 2.72 mmol), DMF (4 ml) were placed in a 10 ml single-necked bottle, reacted at 120 ° C for 8 h, poured into 20 ml of water, extracted with ethyl acetate, combined the organic phases, dried, filtered, and the solvent was evaporated under reduced pressure. After separation by column chromatography (water / acetonitrile = 2:3), a beige solid was obtained, which is the target compound of formula (I-8). N -cyclohexyl-5-(6-methoxypyridin-3-yl)pyrazolo[1,5-a]pyrimidin-7-amine, yield 89%.

[0072] The target compound prepared in this example was characterized, and the characterization data are as follows: Characterization data: 1 H NMR (400 MHz, DMSO- d 6) δ 9.02 (d, J = 2.0 Hz, 1H), 8.48(dd, J = 8.6, 2.6 Hz, 1H), 8.08 (d, J = 2.4 Hz, 1H), 7.56 (d, J= 9.2 Hz,1H), 6.94 (d, J = 8.4 Hz, 1H), 6.77 (s, 1H), 6.45 (d, J = 2.0 Hz, 1H), 3.94(s, 3H), 3.86 – 3.84 (m, 1H), 1.97 – 1.94 (m, 2H), 1.78 – 1.75 (m, 2H), 1.67– 1.64 (m, 1H), 1.55 – 1.44 (m, 4H), 1.21 – 1.15 (m, 1H). 13 C NMR (101 MHz, DMSO- d 6) δ 164.83, 154.22, 149.35, 146.71, 146.58,144.07, 138.30, 128.13, 110.67, 95.22, 81.54, 53.90, 50.67, 32.46, 25.51,25.15. LC-MS: [M+H]+=324.3.

[0073] Preparation Example 9 The synthetic route of this preparation example is as follows:

[0074] The specific steps include: 4,4,4-trifluoro-1-(2-methoxyphenyl)butane-1,3-dione (10 mmol, 2.16 g) and 3-aminopyrazole (11 mmol, 0.91 g) shown in formula (Ⅳ-9) were dissolved in 20 mL of acetic acid, heated to 100°C for reaction for 2 hours. After the reaction was completed, the mixture was poured into water, the solid was precipitated, filtered, and slurried with ethanol to obtain 5-(2-methoxyphenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine shown in formula (Ⅱ-9).

[0075] Example 9 The synthetic route of the present embodiment is as follows:

[0076] Synthesis of N-cyclohexyl-5-(2-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-7-amine: 5-(2-methoxyphenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (0.20 g, 0.68 mmol) of formula (II-9) prepared in Preparation Example 9, cyclohexylamine (0.14 g, 1.36 mmol), Cs2CO3 (0.44 g, 1.36 mmol), CaH2 (0.11 g, 2.72 mmol), DMF (4 ml) were placed in a 10 ml single-mouth bottle, reacted at 120 ° C for 8 h, poured into 20 ml of water, extracted with ethyl acetate, combined the organic phases, dried, filtered, and the solvent was evaporated under reduced pressure. After separation by column chromatography (water / acetonitrile = 2:3), a beige solid was obtained, which is the target compound of formula (I-9). N -cyclohexyl-5-(2-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-7-amine, yield 78%.

[0077] The target compound prepared in this example was characterized, and the characterization data are as follows: Characterization data: 1 H NMR (400 MHz, DMSO- d 6) δ 8.09 (d, J = 2.4 Hz, 1H), 7.76(d, J = 8.0 Hz, 1H), 7.75 – 7.73 (m, 1H), 7.53 (d, J = 8.8 Hz, 1H), 7.42 (t, J = 8.0 Hz, 1H), 7.06 (dd, J = 7.8, 2.2 Hz, 1H), 6.73 (s, 1H), 6.48 (d, J =2.0 Hz, 1H), 3.90 – 3.85 (m, 4H), 1.96 – 1.95 (m, 2H), 1.78 – 1.74 (m, 2H), 1.67 – 1.63 (m, 1H), 1.59 – 1.45 (m, 4H), 1.19 – 1.16 (m, 1H). 13 C NMR (101 MHz, DMSO- d 6) δ 159.95, 156.22, 149.28, 146.52, 144.11,140.38, 130.01, 120.09, 115.56, 112.97, 95.39, 82.31, 55.68, 50.61, 32.49,25.52,25.09. LC-MS: [M+H]+=323.3

[0078] Preparation Example 10 The synthetic route of this preparation example is as follows:

[0079] The specific steps include: 4,4,4-trifluoro-1-(3,4-dimethoxyphenyl)butane-1,3-dione (10 mmol, 2.47 g) and 3-aminopyrazole (12 mmol, 1.00 g) shown in formula (Ⅳ-10) were dissolved in 28 mL of acetic acid, heated to 105°C and reacted for 2.5 hours. After the reaction was completed, poured into water, the solid precipitated, filtered, and slurried with ethanol to obtain 5-(3,4-dimethoxyphenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine shown in formula (Ⅱ-10).

[0080] Example 10

[0081]

[0082] N -cyclohexyl-5-(3,4-dimethoxyphenyl)pyrazolo[1,5-a]pyrimidin-7-amine 5-(3,4-dimethoxyphenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (0.20 g, 0.62 mmol) of formula (II-10) prepared in Preparation Example 10, cyclohexylamine (0.13 g, 1.24 mmol), Cs2CO3 (0.40 g, 1.24 mmol), CaH2 (0.10 g, 2.48 mmol) and DMF (4 ml) were placed in a 10 ml single-necked bottle and reacted at 120 °C for 8 h. The system was poured into 20 ml of water and extracted with ethyl acetate. The organic phases were combined, dried, filtered, and the solvent was evaporated under reduced pressure. The mixture was separated by column chromatography (water / acetonitrile = 2:3) to obtain a beige solid, which was the target compound N-cyclohexyl-5-phenylpyrazolo[1,5-a]pyrimidine-7-amine represented by formula (I-10) with a yield of 84%.

[0083] The target compound prepared in this example was characterized, and its NMR spectrum was as follows: Figure 7 The specific characterization data are as follows: Characterization data: 1 H NMR (400 MHz, DMSO- d 6) δ 8.06 (d, J = 2.0 Hz, 1H), 7.77 –7.75 (m, 2H), 7.45 (d, J= 9.2 Hz, 1H), 7.06 (d, J = 8.8 Hz, 1H), 6.68 (s,1H), 6.44 (d, J = 2.4 Hz, 1H), 3.87 – 3.84 (m, 7H), 1.98 – 1.95 (m, 2H), 1.78 – 1.75 (m, 2H), 1.66 – 1.64 (m, 1H), 1.55 – 1.45 (m, 4H), 1.27 – 1.16 (m,1H). 13 C NMR (101 MHz, DMSO- d 6) δ 156.23, 150.79, 149.30, 149.12, 146.37,143.98, 131.44, 120.70, 111.74, 110.74, 95.07, 81.63, 56.09, 56.04, 50.57,32.48, 25.53, 25.09. LC-MS: [M+H]+=353.2.

[0084] Preparation Example 11 The synthetic route of this preparation example is as follows:

[0085] The specific steps include: 4,4,4-trifluoro-1-(4-bromophenyl)butane-1,3-dione (10 mmol, 2.20 g) and 3-aminopyrazole (11 mmol, 0.91 g) shown in formula (Ⅳ-11) were dissolved in 20 mL of acetic acid, heated to 100°C for reaction for 2 hours. After the reaction was completed, the mixture was poured into water, the solid was precipitated, filtered, and slurried with ethanol to obtain 5-(4-bromophenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine shown in formula (Ⅱ-11).

[0086] Embodiment 11 The synthetic route of the present embodiment is as follows:

[0087] N -Synthesis of cyclohexyl-5-(4-bromophenyl)pyrazolo[1,5-a]pyrimidin-7-amine: 5-(4-bromophenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (0.20 g, 0.59 mmol) of formula (II-11) prepared in Preparation Example 11, cyclohexylamine (0.12 g, 1.18 mmol), Cs2CO3 (0.38 g, 1.18 mmol), CaH2 (0.99 g, 2.36 mmol), DMF (4 ml) were placed in a 10 ml single-mouth bottle, reacted at 120 ° C for 8 h, poured into 20 ml of water, extracted with ethyl acetate, combined the organic phases, dried, filtered, and the solvent was evaporated under reduced pressure. After separation by column chromatography (water / acetonitrile = 2:3), a beige solid was obtained, which is the target compound of formula (I-11). N -cyclohexyl-5-(4-bromophenyl)pyrazolo[1,5-a]pyrimidin-7-amine, yield 91%.

[0088] The target compound prepared in this example was characterized, and the characterization data are as follows: Characterization data: 1 H NMR (400 MHz, DMSO- d 6) δ 8.17 (d, J = 8.4 Hz, 2H), 8.10(s, 1H), 7.69 (d, J = 8.4 Hz, 2H), 7.60 (d, J = 8.8 Hz, 1H), 6.77 (s, 1H), 6.47 (d, J = 2.3 Hz, 1H), 3.86 – 3.85 (m, 1H), 1.96 – 1.91 (m, 2H), 1.77 –1.74 (m, 2H), 1.67 – 1.63 (m, 1H), 1.58 – 1.44 (m, 4H), 1.21 – 1.15 (m, 1H). 13 C NMR (101 MHz, DMSO- d 6) δ 155.14, 149.26, 146.63, 144.20, 137.99,131.86, 129.69, 123.68, 95.47, 81.92, 50.68, 32.46, 25.50, 25.14. LC-MS: [M+H]+=371.1.

[0089] Preparation Example 12 The synthetic route of this preparation example is as follows:

[0090] The specific steps include: 4,4,4-Trifluoro-1-(4-trifluoromethylphenyl)butane-1,3-dione (10 mmol, 2.24 g) and 3-aminopyrazole (11 mmol, 0.91 g) shown in formula (Ⅳ-12) were dissolved in 23 mL of acetic acid, heated to 100°C for reaction for 2 hours. After the reaction was completed, the mixture was poured into water, the solid precipitated, filtered, and slurried with ethanol to obtain 5-(4-trifluoromethylphenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine shown in formula (Ⅱ-12). Example 12

[0091] The synthetic route of the present embodiment is as follows:

[0092] N Synthesis of cyclohexyl-5-(4-trifluoromethylphenyl)pyrazolo[1,5-a]pyrimidin-7-amine 5-(4-trifluoromethylphenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (0.20 g, 0.60 mmol) of formula (II-12) prepared in Preparation Example 12, cyclohexylamine (0.12 g, 1.20 mmol), Cs2CO3 (0.39 g, 1.20 mmol), CaH2 (0.10 g, 2.40 mmol), DMF (4 ml) were placed in a 10 ml single-necked bottle, reacted at 120 °C for 8 h, poured into 20 ml of water, extracted with ethyl acetate, combined the organic phases, dried, filtered, and the solvent was evaporated under reduced pressure. After separation by column chromatography (water / acetonitrile = 2:3), a beige solid was obtained, which was the target compound of formula (I-12). N -cyclohexyl-5-(4-trifluoromethylphenyl)pyrazolo[1,5-a]pyrimidin-7-amine, yield 64%.

[0093] The target compound prepared in this example was characterized, and the characterization data are as follows: Characterization data: 1 H NMR (400 MHz, DMSO- d 6) δ 8.42 (d, J = 8.0 Hz, 2H), 8.13(d, J = 2.0 Hz, 1H), 7.86 (d, J = 8.4 Hz, 2H), 7.69 (d, J = 8.8 Hz, 1H), 6.85(s, 1H), 6.52 (d, J= 2.0 Hz, 1H), 3.89 – 3.87 (m, 1H), 1.97 – 1.95 (m, 2H), 1.78 – 1.75 (m, 2H), 1.67 – 1.64 (m, 1H), 1.57 – 1.44 (m, 4H), 1.18 – 1.15(m, 1H). 13 C NMR (101 MHz, DMSO- d 6) δ 154.74, 149.27, 146.72, 144.34, 142.74,130.17, 129.85, 128.41, 125.82, 125.79, 123.39, 95.76, 82.52, 50.76, 32.44,25.49, 25.15. LC-MS: [M+H]+=361.2.

[0094] Example 13 The synthetic route of the present embodiment is as follows:

[0095] N -Synthesis of cyclopentyl-5-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-7-amine: 5-(4-methoxyphenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (0.20 g, 0.68 mmol) of formula (II-7) prepared in Preparation Example 7, cyclopentylamine (0.12 g, 1.36 mmol), Cs2CO3 (0.44 g, 1.36 mmol), CaH2 (0.11 g, 2.72 mmol), DMF (4 ml) were placed in a 10 ml single-necked bottle, reacted at 120 ° C for 8 h, poured into 20 ml of water, extracted with ethyl acetate, combined the organic phases, dried, filtered, and the solvent was evaporated under reduced pressure. After separation by column chromatography (water / acetonitrile = 2:3), a beige solid was obtained, which is the target compound of formula (I-13). N -cyclopentyl-5-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-7-amine, yield 78%.

[0096] The target compound prepared in this example was characterized, and the characterization data are as follows: Characterization data: 1 H NMR (400 MHz, DMSO- d 6) δ 8.16 (d, J = 8.8 Hz, 2H), 8.06(d,J = 2.4 Hz, 1H), 7.58 (d, J = 7.6 Hz, 1H), 7.05 (d, J = 8.8 Hz, 2H), 6.65(s, 1H), 6.42 (d, J = 2.4 Hz, 1H), 4.30 – 4.25 (m, 1H), 3.83 (s, 3H), 2.09 –2.07 (m, 2H), 1.77 – 1.73 (m, 4H), 1.62 – 1.60 (m, 2H). 13 C NMR (101 MHz, DMSO- d 6) δ 161.05, 156.02, 149.33, 147.05, 143.98,131.15, 129.06, 114.29, 95.01, 82.00, 55.73, 53.44, 32.39, 24.11. LC-MS: [M+H]+=309.2. Embodiment 14

[0097] The synthetic route of the present embodiment is as follows:

[0098] Synthesis of 5-(4-methoxyphenyl)-7-(pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine: 5-(4-methoxyphenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (0.20 g, 0.68 mmol) of formula (II-7) prepared in Preparation Example 7, pyrrolidine (0.10 g, 1.36 mmol), Cs2CO3 (0.44 g, 1.36 mmol), CaH2 (0.11 g, 2 .72mmol), DMF (4ml), placed in a 10ml single-mouth bottle, reacted at 120℃ for 8h, poured into 20ml of water, extracted with ethyl acetate, combined the organic phases, dried, filtered, and the solvent was evaporated under reduced pressure. After separation by column chromatography (water / acetonitrile = 2:3), a beige solid was obtained, which was the target compound 5-(4-methoxyphenyl)-7-(pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine represented by formula (Ⅰ-14), with a yield of 88%.

[0099] The target compound prepared in this example was characterized, and the characterization data are as follows: Characterization data: 1 H NMR (400 MHz, DMSO- d6) δ 8.09 (d, J = 8.8 Hz, 2H), 7.98(d, J = 2.0 Hz, 1H), 7.03 (d, J = 8.8 Hz, 2H), 6.35 (d, J = 2.0 Hz, 1H), 6.32(s, 1H), 4.01 – 3.93 (m, 4H), 3.82 (s, 3H), 1.98 – 1.95 (m, 4H). 13 C NMR (101 MHz, DMSO- d 6) δ 161.02, 155.85, 151.54, 147.91, 143.95,130.93, 128.87, 114.27, 94.09, 85.28, 55.71, 51.04, 25.40. LC-MS: [M+H]+=295.2. Embodiment 15

[0100] The synthetic route of the present embodiment is as follows:

[0101] N Synthesis of butyl-5-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-7-amine: 5-(Pyridin-2-yl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (0.20 g, 0.68 mmol) of formula (II-7) prepared in Preparation Example 7, n-butylamine (0.10 g, 1.36 mmol), Cs2CO3 (0.44 g, 1.36 mmol), CaH2 (0.11 g, 2.72 mmol), DMF (4 ml) were placed in a 10 ml single-necked bottle, reacted at 120 ° C for 8 h, poured into 20 ml of water, extracted with ethyl acetate, combined the organic phases, dried, filtered, and the solvent was evaporated under reduced pressure. After separation by column chromatography (water / acetonitrile = 2:3), a beige solid was obtained, which is the target compound of formula (I-15). N -Butyl-5-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-7-amine, yield 94%.

[0102] The target compound prepared in this example was characterized, and its NMR spectrum was as follows: Figure 8 The specific characterization data are as follows: Characterization data: 1H NMR (400 MHz, DMSO- d 6) δ 8.15 (d, J = 8.8 Hz, 2H), 8.06(d, J = 2.0 Hz, 1H), 7.88 (t, J = 6.0 Hz, 1H), 7.04 (d, J = 9.2 Hz, 2H), 6.61(s, 1H), 6.41 (d, J = 2.4 Hz, 1H), 3.83 (s, 3H), 3.50 (q, J = 6.8 Hz, 2H),1.68 – 1.65 (m, 2H), 1.43 – 1.37 (m, 2H), 0.93 (t, J = 7.4 Hz, 3H). 13 C NMR (101 MHz, DMSO- d 6) δ 161.03, 156.03, 149.33, 147.42, 144.04,131.19, 129.02, 114.29, 94.93, 81.26, 55.71, 41.42, 31.08, 20.03, 14.21. LC-MS: [M+H]+=297.2. Example 16

[0103] The synthetic route of the present embodiment is as follows:

[0104] Synthesis of 4-((5-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-7-yl)amino)-2-methylpropan-2-ol: 5-(4-methoxyphenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (0.20 g, 0.68 mmol) of formula (II-7) prepared in Preparation Example 7, 4-amino-2-methylpropan-2-ol (0.14 g, 1.36 mmol), Cs2CO3 (0.44 g, 1.36 mmol), CaH2 (0. 11g, 2.72mmol), DMF (4ml), placed in a 10ml single-mouth bottle, reacted at 120℃ for 8h, poured into 20ml of water, extracted with ethyl acetate, combined the organic phases, dried, filtered, and the solvent was evaporated under reduced pressure. The mixture was separated by column chromatography (water / acetonitrile = 2:3) to obtain a beige solid, which is the target compound 4-((5-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-7-yl)amino)-2-methylpropan-2-ol represented by formula (Ⅰ-16), with a yield of 52%.

[0105] The target compound prepared in this example was characterized, and the characterization data are as follows: Characterization data: 1 H NMR (400 MHz, DMSO- d 6) δ 8.15 (d, J = 8.8 Hz, 2H), 8.08(d, J = 2.0 Hz, 1H), 7.29 (t, J = 6.2 Hz, 1H), 7.05 (d, J = 8.8 Hz, 2H), 6.78(s, 1H), 6.44 (d, J = 2.0 Hz, 1H), 4.87 (s, 1H), 3.84 (s, 3H), 3.47 (d, J =6.4 Hz, 2H), 1.23 (s, 6H). 13 C NMR (101 MHz, DMSO- d 6) δ 161.07, 156.09, 149.12, 147.81, 144.16,131.15, 129.03, 114.29, 95.06, 82.03, 69.99, 55.73, 52.46, 27.73. LC-MS: [M+H]+=313.1. Embodiment 17

[0106] The synthetic route of the present embodiment is as follows:

[0107] 5-(4-methoxyphenyl)- N Synthesis of -(1-phenylethyl)pyrazolo[1,5-a]pyrimidin-7-amine: 5-(4-methoxyphenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (0.20 g, 0.68 mmol) of formula (II-7) prepared in Preparation Example 7, phenethylamine (0.16 g, 1.36 mmol), Cs2CO3 (0.44 g, 1.36 mmol), CaH2 (0.11 g, 2.72 mmol), and DMF (4 ml) were placed in a 10 ml single-necked bottle and reacted at 120 °C for 8 h. The system was poured into 20 ml of water and extracted with ethyl acetate. The organic phases were combined, dried, filtered, and the solvent was evaporated under reduced pressure. The mixture was separated by column chromatography (water / acetonitrile = 2:3) to obtain a beige solid, which is the target compound 5-(4-methoxyphenyl)- N -(1-phenylethyl)pyrazolo[1,5-a]pyrimidin-7-amine, yield 92%.

[0108] The target compound prepared in this example was characterized, and the characterization data are as follows: Characterization data: 1 H NMR (400 MHz, DMSO- d 6) δ 8.25 (d, J = 8.4 Hz, 1H), 8.11(d, J = 2.0 Hz, 1H), 8.01 (d, J = 8.8 Hz, 2H), 7.58 (d, J = 7.6 Hz, 2H), 7.34(t, J = 7.6 Hz, 2H), 7.23 (t, J = 7.6 Hz, 1H), 7.02 (d, J = 8.8 Hz, 2H), 6.52(s, 1H), 6.44 (d, J = 2.0 Hz, 1H), 5.18 (t, J = 7.4 Hz, 1H), 3.81 (s, 3H), 1.67 (d, J = 6.8 Hz, 3H). 13 C NMR (101 MHz, DMSO- d6) δ 161.08, 155.80, 149.33, 146.61, 144.41,144.12, 130.94, 128.99, 128.83, 127.60, 126.57, 114.38, 95.14, 82.62, 55.72,51.58, 23.41. LC-MS: [M+H]+=345.1. Embodiment 18

[0109] The synthetic route of the present embodiment is as follows:

[0110] N -Synthesis of benzyl-5-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-7-amine 5-(4-methoxyphenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (0.20 g, 0.68 mmol) of formula (II-7) prepared in Preparation Example 7, benzylamine (0.15 g, 1.36 mmol), Cs2CO3 (0.44 g, 1.36 mmol), CaH2 (0.11 g, 2.72 mmol), DMF (4 ml) were placed in a 10 ml single-necked bottle, reacted at 120 ° C for 8 h, poured into 20 ml of water, extracted with ethyl acetate, combined the organic phases, dried, filtered, and the solvent was evaporated under reduced pressure. After separation by column chromatography (water / acetonitrile = 2:3), a beige solid was obtained, which is the target compound of formula (I-18). N -Benzyl-5-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-7-amine, yield 94%.

[0111] The target compound prepared in this example was characterized, and the characterization data are as follows: Characterization data: 1 H NMR (400 MHz, DMSO- d 6) δ 8.63 (t, J = 6.6 Hz, 1H), 8.10(d, J = 2.0 Hz, 1H), 8.05 (d, J = 8.8 Hz, 2H), 7.48 (d, J = 7.6 Hz, 2H), 7.34(t, J = 7.6 Hz, 2H), 7.23 (t, J = 7.4 Hz, 1H), 7.03 (d, J= 9.2 Hz, 2H), 6.58(s, 1H), 6.44 (d, J = 2.4 Hz, 1H), 4.76 (d, J = 6.4 Hz, 2H), 3.81 (s, 3H). 13 C NMR (101 MHz, DMSO- d 6) δ 161.07, 155.85, 149.32, 147.38, 144.26,138.98, 130.97, 128.94, 128.88, 127.65, 127.60, 114.36, 95.08, 81.96, 55.72,44.82. LC-MS: [M+H]+=331.1. Embodiment 19

[0112] The synthetic route of the present embodiment is as follows:

[0113] Synthesis of 5-(4-methoxyphenyl)-N-(thiophen-2-ylmethyl)pyrazolo[1,5-a]pyrimidin-7-amine: 5-(4-methoxyphenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (0.20 g, 0.68 mmol) of formula (II-7) prepared in Preparation Example 7, 2-thiophenemethylamine (0.15 g, 1.36 mmol), Cs2CO3 (0.44 g, 1.36 mmol), CaH2 (0.11 g, 2.72 mmol), and DMF (4 ml) were placed in a 10 ml single-necked bottle and reacted at 120 °C for 8 h. The system was poured into 20 ml of water and extracted with ethyl acetate. The organic phases were combined, dried, filtered, and the solvent was evaporated under reduced pressure. The mixture was separated by column chromatography (water / acetonitrile = 2:3) to obtain a beige solid, which was the target compound 5-(4-methoxyphenyl)-N-(thiophen-2-ylmethyl)pyrazolo[1,5-a]pyrimidine-7-amine of formula (I-19) in a yield of 67%.

[0114] The target compound prepared in this example was characterized, and the characterization data are as follows: Characterization data: 1 H NMR (400 MHz, DMSO- d 6) δ 8.59 (t, J = 6.4 Hz, 1H), 8.12 –8.09 (m, 3H), 7.41 (d, J= 4.4, 1H), 7.24 (d, J = 2.8 Hz, 1H), 7.s06 (d, J =8.8 Hz, 2H), 6.99 (dd, J = 5.2, 3.6 Hz, 1H), 6.75 (s, 1H), 6.44 (d, J = 2.4Hz, 1H), 4.95 (d, J = 6.4 Hz, 2H), 3.83 (s, 3H). LC-MS: [M+H]+=337.1.

[0115] Embodiment 20 The synthetic route of the present embodiment is as follows:

[0116] Synthesis of 5-(4-methoxyphenyl)-N-(furan-2-ylmethyl)pyrazolo[1,5-a]pyrimidin-7-amine: 5-(4-methoxyphenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (0.20 g, 0.68 mmol) of formula (II-7) prepared in Preparation Example 7, 2-furanmethylamine (0.14 g, 1.36 mmol), Cs2CO3 (0.44 g, 1.36 mmol), CaH2 (0.11 g, 2.72mmol), DMF (4ml), placed in a 10ml single-mouth bottle, reacted at 120℃ for 8h, poured into 20ml of water, extracted with ethyl acetate, combined the organic phases, dried, filtered, and the solvent was evaporated under reduced pressure. The mixture was separated by column chromatography (water / acetonitrile = 2:3) to obtain a beige solid, which is the target compound 5-(4-methoxyphenyl)-N-(furan-2-ylmethyl)pyrazolo[1,5-a]pyrimidin-7-amine represented by formula (Ⅰ-20), with a yield of 45%.

[0117] The target compound prepared in this example was characterized, and the characterization data are as follows: Characterization data: 1 H NMR (400 MHz, DMSO- d 6) δ 8.39 (t, J = 6.2 Hz, 1H), 8.12(d, J = 8.8 Hz, 2H), 8.08 (d, J = 2.0 Hz, 1H), 7.61 (dd, J = 1.8, 0.8 Hz,1H), 7.06 (d, J= 9.2 Hz, 2H), 6.77 (s, 1H), 6.48 (d, J = 2.8 Hz, 1H), 6.44(d, J = 2.0 Hz, 1H), 6.41 (dd, J = 3.2, 2.0 Hz, 1H), 4.76 (d, J = 6.4 Hz,2H), 3.84 (s, 3H). LC-MS: [M+H]+=321.1. Preparation Example 13

[0118] The synthetic route of this preparation example is as follows:

[0119] The specific steps include: The compound represented by formula (Ⅳ-13) (10 mmol, 2.43 g) and 3-aminopyrazole (13 mmol, 1.08 g) were dissolved in 28 mL of acetic acid, and the temperature was raised to 90°C for reaction for 3 h. After the reaction was completed, the mixture was poured into water, the precipitated solid was filtered, and slurried with ethanol to obtain N-(4-(7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-5-yl)phenyl)acetamide represented by formula (Ⅱ-13). Embodiment 21

[0120] The synthetic route of the present embodiment is as follows:

[0121] Synthesis of N-(4-(7-(cyclohexylamino)pyrazolo[1,5-a]pyrimidin-5-yl)phenyl)acetamide: N-(4-(7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-5-yl)phenyl)acetamide (0.20 g, 0.63 mmol) of formula (II-13) prepared in Preparation Example 13, cyclohexylamine (0.13 g, 1.26 mmol), Cs2CO3 (0.41 g, 1.26 mmol), CaH2 (0.10 g, 2.52mmol), DMF (4ml), placed in a 10ml single-mouth bottle, reacted at 120℃ for 8h, poured into 20ml of water, extracted with ethyl acetate, combined the organic phases, dried, filtered, and the solvent was evaporated under reduced pressure. After separation by column chromatography (water / acetonitrile = 2:3), a beige solid was obtained, which was the target compound N-(4-(7-(cyclohexylamino)pyrazolo[1,5-a]pyrimidin-5-yl)phenyl)acetamide represented by formula (Ⅰ-21), with a yield of 83%.

[0122] The target compound prepared in this example was characterized, and the characterization data are as follows: Characterization data: 1 H NMR (400 MHz, DMSO- d 6) δ 10.15 (s, 1H), 8.16 (d, J = 8.8Hz, 2H), 8.06 (d, J = 2.0 Hz, 1H), 7.72 (d, J = 8.8 Hz, 2H), 7.48 (d, J = 9.2Hz, 1H), 6.71 (s, 1H), 6.43 (d, J = 2.4 Hz, 1H), 3.85 – 3.83 (m, 1H), 2.09(s, 3H), 1.99 – 1.95 (m, 2H), 1.78 – 1.75 (m, 2H), 1.67 – 1.64 (m, 1H), 1.52– 1.48 (m, 4H), 1.19 – 1.18 (m, 1H). LC-MS: [M+H]+=350.2.

[0123] Preparation Example 14

[0124] The synthetic route of this preparation example is as follows:

[0125] The specific steps include: 4,4,4-trifluoro-1-(3-methoxyphenyl)butane-1,3-dione (10 mmol, 2.15 g) and 3-aminopyrazole (11 mmol, 0.99 g) shown in formula (Ⅳ-14) were dissolved in 20 mL of acetic acid, heated to 100°C for reaction for 2 hours. After the reaction was completed, poured into water, the solid precipitated, filtered, and slurried with ethanol to obtain 5-(3-methoxyphenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine shown in formula (Ⅱ-14).

[0126] Embodiment 22 The synthetic route of the present embodiment is as follows:

[0127] Synthesis of N-cyclohexyl-5-(3-methoxyphenyl)pyrazolo[1,5-a]pyrimidine-7-amine: 5-(3-methoxyphenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (0.20 g, 0.68 mmol) of formula (II-14) prepared in Preparation Example 14, cyclohexylamine (0.13 g, 1.36 mmol), Cs2CO3 (0.44 g, 1.36 mmol), CaH2 (0.11 g, 2 .72mmol), DMF (4ml), placed in a 10ml single-mouth bottle, reacted at 120℃ for 8h, poured into 20ml of water, extracted with ethyl acetate, combined the organic phases, dried, filtered, and the solvent was evaporated under reduced pressure. After separation by column chromatography (water / acetonitrile = 2:3), a beige solid was obtained, which is the target compound N-cyclohexyl-5-(3-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-7-amine represented by formula (Ⅰ-22), with a yield of 88%.

[0128] The target compound prepared in this example was characterized, and its NMR spectrum was as follows: Fig. 9 The specific characterization data are as follows: Characterization data: 1 H NMR (400 MHz, DMSO- d 6) δ 8.09 (d, J = 2.4 Hz, 1H), 7.72(dd, J = 7.8, 1.8 Hz, 1H), 7.50 (d, J = 8.4 Hz, 1H), 7.43 (ddd, J = 9.2, 7.6,1.6 Hz, 1H), 7.16 (d, J = 8.0 Hz, 1H), 7.06 (t, J = 7.5 Hz, 1H), 6.58 (s,1H), 6.44 (d, J = 2.0 Hz, 1H), 3.84 (s, 3H), 3.57 – 3.55 (m, 1H), 2.00 – 1.98(m, 2H), 1.78 – 1.75 (m, 2H), 1.65 – 1.62(m, 1H), 1.54 – 1.48 (m, 2H), 1.44 –1.38 (m, 2H), 1.23 – 1.146 (m, 1H). 13 C NMR (101 MHz, DMSO- d6) δ 157.36, 156.06, 149.34, 145.53, 143.81,130.87, 130.81, 128.94, 120.95, 112.54, 95.10, 87.04, 56.12, 51.19, 32.22,25.55, 25.07. LC-MS: [M+H]+=323.2. Embodiment 23

[0129] The synthetic route of the present embodiment is as follows:

[0130] Synthesis of N-(4-methoxybenzyl)-5-(4-methylphenyl)pyrazolo[1,5-a]pyrimidin-7-amine: 5-(4-methylphenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (0.20 g, 0.68 mmol) of formula (II-7) prepared in Preparation Example 7, p-methoxybenzylamine (0.16 g, 1.36 mmol), Cs2CO3 (0.44 g, 1.36 mmol), CaH2 (0.11 g, 2 .72mmol), DMF (4ml), placed in a 10ml single-mouth bottle, reacted at 120℃ for 8h, poured into 20ml of water, extracted with ethyl acetate, combined the organic phases, dried, filtered, and the solvent was evaporated under reduced pressure. After separation by column chromatography (water / acetonitrile = 2:3), a beige solid was obtained, which is the target compound N-(4-methoxybenzyl)-5-(4-methylphenyl)pyrazolo[1,5-a]pyrimidin-7-amine represented by formula (Ⅰ-23), with a yield of 95%.

[0131] The target compound prepared in this example was characterized, and the characterization data are as follows: Characterization data: 1 H NMR (400 MHz, DMSO- d 6) δ 8.54 (t, J = 6.6 Hz, 1H), 8.09(d, J = 2.4 Hz, 1H), 8.06 (d, J = 8.8 Hz, 2H), 7.42 (d, J = 8.8 Hz, 2H), 7.04(d, J = 8.8 Hz, 2H), 6.90 (d, J = 8.4 Hz, 2H), 6.60 (s, 1H), 6.43 (d, J = 2.0Hz, 1H), 4.67 (d,J = 6.8 Hz, 2H), 3.82 (s, 3H), 3.70 (s, 3H). 13 C NMR (101 MHz, DMSO- d 6) δ 161.07, 158.86, 155.82, 149.31, 147.28,144.20, 131.01, 130.80, 129.07, 128.89, 114.37, 114.30, 95.04, 81.99, 55.72,55.45, 44.27. LC-MS: [M+H]+=361.2. Embodiment 24

[0132] The synthetic route of the present embodiment is as follows:

[0133] N Synthesis of -(4-bromobenzyl)-5-(4-methylphenyl)pyrazolo[1,5-a]pyrimidin-7-amine: 5-(4-methylphenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (0.20 g, 0.68 mmol) of formula (II-7) prepared in Preparation Example 7, p-bromobenzylamine (0.17 g, 1.36 mmol), Cs2CO3 (0.44 g, 1.36 mmol), CaH2 (0.11 g, 2.72 mmol), DMF (4 ml) were placed in a 10 ml single-mouth bottle, reacted at 120 ° C for 8 h, poured into 20 ml of water, extracted with ethyl acetate, combined the organic phases, dried, filtered, and the solvent was evaporated under reduced pressure. After separation by column chromatography (water / acetonitrile = 2:3), a beige solid was obtained, which is the target compound of formula (I-24). N -(4-bromobenzyl)-5-(4-methylphenyl)pyrazolo[1,5-a]pyrimidin-7-amine, yield 35%.

[0134] The target compound prepared in this example was characterized, and the characterization data are as follows: Characterization data: 1 H NMR (400 MHz, DMSO- d 6) δ 8.64 (t, J = 6.6 Hz, 1H), 8.10(d, J = 2.0 Hz, 1H), 8.06 (d, J = 8.8 Hz, 2H), 7.54 (d, J= 8.4 Hz, 2H), 7.44(d, J = 8.0 Hz, 2H), 7.03 (d, J = 9.2 Hz, 2H), 6.58 (s, 1H), 6.45 (d, J = 2.0Hz, 1H), 4.74 (d, J = 6.8 Hz, 2H), 3.82 (s, 3H). 13 C NMR (101 MHz, DMSO- d 6) δ 161.10, 155.90, 149.31, 147.29, 144.29,138.50, 131.81, 130.92, 129.89, 128.92, 120.64, 114.36, 95.12, 81.88, 55.72,44.14. LC-MS: [M+H]+=395.0. Embodiment 25

[0135] The synthetic route of the present embodiment is as follows:

[0136] N Synthesis of -(2-bromobenzyl)-5-(4-methylphenyl)pyrazolo[1,5-a]pyrimidin-7-amine: 5-(4-methylphenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (0.20 g, 0.68 mmol) of formula (II-7) prepared in Preparation Example 7, o-bromobenzylamine (0.17 g, 1.36 mmol), Cs2CO3 (0.44 g, 1.36 mmol), CaH2 (0.11 g, 2.72 mmol), DMF (4 ml) were placed in a 10 ml single-mouth bottle, reacted at 120 ° C for 8 h, poured into 20 ml of water, extracted with ethyl acetate, combined the organic phases, dried, filtered, and the solvent was evaporated under reduced pressure. After separation by column chromatography (water / acetonitrile = 2:3), a beige solid was obtained, which is the target compound of formula (I-25). N -(2-Bromobenzyl)-5-(4-methylphenyl)pyrazolo[1,5-a]pyrimidin-7-amine, yield 45%.

[0137] The target compound prepared in this example was characterized, and its NMR spectrum was as follows: Fig.10 The specific characterization data are as follows: Characterization data: 1H NMR (400 MHz, DMSO- d 6) δ 8.65 (t, J = 6.6 Hz, 1H), 8.11(d, J = 2.4 Hz, 1H), 8.08 (d, J = 8.8 Hz, 2H), 7.71 (s, 1H), 7.49 (d, J = 7.6Hz, 1H), 7.45 (d, J = 8.8 Hz, 1H), 7.31 (t, J = 7.8 Hz, 1H), 7.03 (d, J = 8.8Hz, 2H), 6.63 (s, 1H), 6.45 (d, J = 2.4 Hz, 1H), 4.76 (d, J = 6.8 Hz, 2H),3.82 (s, 3H). 13 C NMR (101 MHz, DMSO- d 6) δ 161.12, 155.93, 149.31, 147.26, 144.33,141.95, 131.13, 130.91, 130.53, 130.47, 128.94, 126.74, 122.22, 114.35,95.16, 81.87, 55.73, 44.12. LC-MS: [M+H]+=395.0. Embodiment 26

[0138] The product and the synthesis method are basically the same as those in Example 1, and the specific difference can be seen in the preparation method: The synthetic route is the same as that of Example 1.

[0139] N -Synthesis of cyclohexyl-5-phenylpyrazolo[1,5-a]pyrimidin-7-amine: 5-(Phenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (0.20 g, 0.76 mmol) of formula (II-1) prepared in Preparation Example 1, cyclohexylamine (0.11 g, 1.14 mmol), K2CO3 (0.21 g, 1.52 mmol), NaH (0.04 g, 1.52 mmol), DMAC (5 ml) were placed in a 10 ml single-necked bottle, reacted at 100 °C for 9 h, poured into 20 ml of water, extracted with ethyl acetate, the organic phases were combined, dried, filtered, the solvent was evaporated under reduced pressure, and separated by column chromatography (water / acetonitrile = 2:3) to obtain the target compound of formula (I-1) as a beige solid. N -cyclohexyl-5-phenylpyrazolo[1,5-a]pyrimidin-7-amine, yield 65%. Embodiment 27

[0140] The product and the synthesis method are basically the same as those in Example 1, and the specific difference can be seen in the preparation method: The synthetic route is the same as that of Example 1.

[0141] N -Synthesis of cyclohexyl-5-phenylpyrazolo[1,5-a]pyrimidin-7-amine: 5-(Phenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (0.20 g, 0.76 mmol) of formula (II-1) prepared in Preparation Example 1, cyclohexylamine (0.23 g, 2.28 mmol), NaOH (0.03 g, 0.76 mmol), CaH2 (0.03 g, 0.76 mmol), DMF (4 ml) were placed in a 10 ml single-necked bottle, reacted at 130 °C for 8 h, poured into 20 ml of water, extracted with ethyl acetate, the organic phases were combined, dried, filtered, the solvent was evaporated under reduced pressure, and separated by column chromatography (water / acetonitrile = 2:3) to obtain the target compound of formula (I-1) as a beige solid. N -cyclohexyl-5-phenylpyrazolo[1,5-a]pyrimidin-7-amine, yield 61%. Embodiment 28

[0142] The product and the synthesis method are basically the same as those in Example 6, and the specific difference can be seen in the preparation method: The synthetic route is the same as that of Example 6.

[0143] N -Synthesis of cyclohexyl-5-(4-(methylsulfonyl)phenyl)pyrazolo[1,5-a]pyrimidin-7-amine: 5-(4-(methylsulfonyl)phenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (0.20 g, 0.59 mmol) of formula (II-6) prepared in Preparation Example 6, cyclohexylamine (0.15 g, 1.48 mmol), Cs2CO3 (1.537 g, 4.72 mmol), toluene (4 ml) were placed in a 15 ml single-necked bottle, reacted at 90 °C for 10 h, poured into 20 ml of water, extracted with ethyl acetate, combined the organic phases, dried, filtered, and the solvent was evaporated under reduced pressure. After separation by column chromatography (water / acetonitrile = 2:3), a beige solid was obtained, which was the target compound of formula (I-6). N -cyclohexyl-5-(4-(methylsulfonyl)phenyl)pyrazolo[1,5-a]pyrimidin-7-amine, yield 51%. Embodiment 29

[0144] The product and the synthesis method are basically the same as those in Example 6, and the specific difference can be seen in the preparation method: The synthetic route is the same as that of Example 6.

[0145] N -Synthesis of cyclohexyl-5-(4-(methylsulfonyl)phenyl)pyrazolo[1,5-a]pyrimidin-7-amine: 5-(4-(methylsulfonyl)phenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine (0.20 g, 0.59 mmol) of formula (II-6) prepared in Preparation Example 6, cyclohexylamine (0.12 g, 1.18 mmol), CaH2 (0.15 g, 3.54 mmol), DMF (4 ml) were placed in a 10 ml single-mouth bottle, reacted at 120 ° C for 8 hours, poured into 20 ml of water, extracted with ethyl acetate, combined organic phases, dried, filtered, and the solvent was evaporated under reduced pressure. After separation by column chromatography (water / acetonitrile = 2:3), a beige solid was obtained, which is the target compound of formula (I-6). N -cyclohexyl-5-(4-(methylsulfonyl)phenyl)pyrazolo[1,5-a]pyrimidin-7-amine, yield 47%.

Claims

1. A method for synthesizing a pyrazolo[1,5-a]pyrimidine-7-amine compound, characterized in that: The following steps are involved: The 5-substituted-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine of formula II and the substituted amine of formula III are added to a solvent, an inorganic base catalyst is added thereto, and the reaction is carried out at a set temperature. After the reaction is completed, further post-treatment is carried out to obtain the pyrazolo[1,5-a]pyrimidine-7-amine compound of formula I; The specific synthetic route is as follows: ； Wherein: R1 is selected from: substituted or unsubstituted C6~C10 aryl, substituted or unsubstituted C5~C10 heteroaryl; R2 is selected from: H, substituted aryl-2-ylmethyl; R3 is selected from: substituted or unsubstituted C1~C6 alkyl, substituted or unsubstituted C3~C7 cycloalkyl.

2. The synthesis method according to claim 1, characterized in that The R1 is selected from: a substituted or unsubstituted benzene ring, a naphthalene ring, furan, thiophene, pyridine, oxazole, isoxazole, thiazole, isothiophene, pyrrole, imidazole, pyrazole, pyrimidine, pyrazine, pyridazine; wherein the substitution refers to substitution by one or more groups selected from the following group, and the substituents include but are not limited to: halogen, hydroxyl, amino, carboxyl, cyano, nitro, methanesulfonyl, sulfamoyl, trifluoromethyl, substituted or unsubstituted C1~C6 alkyl, substituted or unsubstituted C3~C7 cycloalkyl, substituted or unsubstituted C1~C6 alkoxy, (C1~C4 alkyl)NH-, di(C1~C4 alkyl)amino; R2 is selected from the group consisting of: H, substituted benzyl, substituted thien-2-ylmethyl, substituted furan-2-ylmethyl.

3. The synthesis method according to claim 1, characterized in that The molar ratio of the 5-substituted-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine shown in formula II to the substituted amine shown in formula III is 1:1-1:3; the molar ratio of the 5-substituted-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine shown in formula II to the inorganic base is 1:0.5-8.

4. The synthesis method according to claim 1 or 3, characterized in that The inorganic base is selected from one or more of K2CO3, Cs2CO3, NaH, CaH2, NaOH, KOH; the solvent is selected from dimethyl sulfoxide, N,N -dimethylformamide, N,N -Dimethylacetamide, N -Methyl pyrrolidone, 1,4-dioxane, toluene or one or more mixtures thereof.

5. The synthesis method according to claim 4, characterized in that The inorganic base is a combination of Cs2CO3 and CaH2, wherein the molar ratio of Cs2CO3 to CaH2 is 1:0.5-1:3; the solvent is N,N -Dimethylformamide.

6. The synthesis method according to claim 1, characterized in that The reaction temperature is 80-130°C and the reaction time is 6-10h.

7. The synthesis method according to claim 1, characterized in that The post-treatment specifically includes extraction, drying, reduced pressure distillation, elution, and column chromatography separation steps; the elution adopts eluents of water and acetonitrile, and the volume ratio of the two is (1-2): (1-3).

8. The synthesis method according to claim 1, characterized in that The preparation method of the 5-R1 substituent-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine shown in formula II comprises the following steps: Dissolve 4,4,4-trifluoro-1-substituted butane-1,3-dione and 3-aminopyrazole in a solvent, raise the temperature to the reaction temperature, and after the reaction is completed, pour into water, precipitate solid, filter, and slurry with ethanol to obtain 5-substituted-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine shown in formula II; The synthetic route is as follows: 。 9. The synthesis method according to claim 8, characterized in that The solvent is acetic acid, the molar ratio of 4,4,4-trifluoro-1-substituted butane-1,3-dione shown in formula IV and 3-aminopyrazole is 1:1-1.3; the reaction temperature is 90-110° C., and the reaction time is 1.5-3 hours.

10. Use of the pyrazolo[1,5-a]pyrimidine-7-amine compound of formula I prepared by the synthesis method according to any one of claims 1 to 9 in the field of medicines or pesticides.

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