A novel 4-(1H-pyrrol-3-yl)pyrimidine anti-breast cancer compound and a preparation method thereof

Abstract

The application belongs to the technical field of medicines, and relates to a novel 4-(1 H pyrrole-3-yl) pyrimidine anti-breast cancer compound and a preparation method thereof. The heterocyclic system of the application is different from the common known inhibitor parent nucleus, the pyrimidine ring of the application can interact with the catalytic domain as a key pharmacophore, and the introduction of the pyrrole ring provides a flexible modification site for exploring allosteric regulation or fine regulation of molecular physical and chemical properties. The application aims to efficiently optimize the structure-activity relationship of the skeleton, and the target is to significantly improve the selectivity of the application to the enzymes of the same family while maintaining the high-efficiency inhibitory activity to USP7, and to systematically improve the pharmacokinetic properties of the compound.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology and relates to a novel 4-(1 H -pyrrole-3-yl)pyrimidine anti-breast cancer compounds and their preparation methods. Background Technology

[0002] Ubiquitin-specific protease 7 (USP7) is a key regulator of the intracellular ubiquitin-proteasome system. By deubiquitinizing and stabilizing important substrates such as MDM2 and DNMT1, it drives tumorigenesis and development at multiple levels, including p53 pathway dysregulation, epigenetic abnormalities, and immune surveillance escape. It has become a well-validated anti-tumor drug target.

[0003] Despite its enormous therapeutic potential, drug development in this field still faces significant challenges. On the one hand, the high conservation of the catalytic domains of the deubiquitinase family makes it difficult for most existing inhibitors targeting the USP7 active site to avoid off-target effects on other family members (such as USP5 and USP8), resulting in potential toxicity risks due to poor selectivity. On the other hand, many reported lead compounds have significant defects in drug-likeness, such as poor metabolic stability and low oral bioavailability, which seriously hinder their translation into clinical research.

[0004] Therefore, developing novel inhibitor skeletons that combine high selectivity and excellent pharmacokinetic properties is key to advancing this field. Summary of the Invention

[0005] In view of the above-mentioned technical problems, the present invention provides a novel 4-(1 H (-pyrrolo-3-yl)pyrimidine anti-breast cancer compounds and their preparation methods. The prepared compounds showed good results in in vitro antitumor activity tests.

[0006] To achieve the above objectives, the present invention adopts the following technical solution.

[0007] A novel 4-(1 H -pyrrolo-3-yl)pyrimidine anti-breast cancer compounds, as shown in general formulas I and II: in: Each R1 is independently dimethylamino, diethylamino, pyrrolyl, N,N,N-trimethylethane-1,2-diamino, morpholinyl, thiomorpholinyl, N-methylpiperazinyl, 4-methylpiperidinyl, N,N,-dimethylpiperidin-4-amino, N-isopropylpiperazinyl, N-ethylpiperazinyl, 4-methoxypiperidinyl, N-methanesulfonylpiperazinyl, 4-trifluoromethylpiperidinyl, 4,4-difluoropiperidinyl, 4-cyclopropylpiperazinyl, N-(oxecyclobutane-3-yl)piperazinyl, 4-(4-piperidinyl)morpholinyl, 2-oxa-6-aza-spiro[3,3]heptyl, 3,9-diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester, 1-tert-butoxycarbonylpiperazinyl, 1-Boc-hexahydro-1,4-diazacycloheptyl 4-Methyl-1,4-diazacycloheptyl, 3,9-diazaspiro[5.5]undecane-3-yl, piperazinyl, homopiperazinyl; Each R2 is independently benzyloxy, hydroxy, diethylamino, N,N,N-trimethylethane-1,2-diamino, N-methylpiperazinyl, 4-methylpiperidinyl, N,N,-dimethylpiperidin-4-amino, 4-methoxypiperidinyl, N-methanesulfonylpiperazinyl, 4-trifluoromethylpiperidinyl, 4,4-difluoropiperidinyl, N-(oxetane-3-yl)piperazinyl, 4-(4- Piperidinyl)morpholinyl, 4-methyl-1,4-diazacycloheptyl, 2-oxa-6-aza-spiro[3,3]heptyl, 1-tert-butoxycarbonylpiperazinyl, 1-Boc-hexahydro-1,4-diazacycloheptyl, 3,9-diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester, piperazinyl, high-piperazinyl, 3,9-diazaspiro[5.5]undecane-3-yl.

[0008] Furthermore, the new compounds represented by general formulas I and II include 4-(1 H 3-pyrrolo-3-yl)pyrimidine compounds and their derivatives, tautomers, and pharmaceutically acceptable salts, hydrates, or solvates.

[0009] Furthermore, compounds of general formula I and general formula II, or their pharmaceutically acceptable salts, hydrates, or solvates, are: (1) 4-(2-((6-(dimethylamino)pyridin-3-yl)amino)pyrimidin-4-yl)- N,N, 1-Trimethyl-1 H -Pyrrole-2-carboxamide; (2) 4-(2-((6-(diethylamino)pyridin-3-yl)amino)pyrimidin-4-yl)- N,N, 1-Trimethyl-1 H -Pyrrole-2-carboxamide; (3) N,N 1-Trimethyl-4-(2-((6-(pyrrolidin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)-1 H -Pyrrole-2-carboxamide; (4) 4-(2-((6-((2-(dimethylamino)ethyl)(methyl)amino)pyridin-3-yl)amino)pyrimidin-4-yl)- N,N, 1-Trimethyl-1 H -Pyrrole-2-carboxamide; (5) N,N 1-Trimethyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1 H -Pyrrole-2-carboxamide; (6) N,N 1-Trimethyl-4-(2-((6-thiomorpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1 H -Pyrrole-2-carboxamide; (7) N,N 1-Trimethyl-4-(2-((6-(4-methylpiperazin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)-1 H -Pyrrole-2-carboxamide; (8) N,N 1-Trimethyl-4-(2-((6-(4-methylpiperidin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)-1 H -pyrrole-2-carboxamide (9) 4-(2-((6-(4-(dimethylamino)piperidin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)- N,N, 1-Trimethyl-1 H -Pyrrole-2-carboxamide; (10) 4-(2-((6-(4-isopropylpiperazin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)- N,N, 1-Trimethyl-1 H -Pyrrole-2-carboxamide; (11) 4-(2-((6-(4-ethylpiperazin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)- N,N, 1-Trimethyl-1 H -Pyrrole-2-carboxamide; (12) 4-(2-((6-(4-methoxypiperidin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)- N,N, 1-Trimethyl-1 H -Pyrrole-2-carboxamide; (13) N,N 1-Trimethyl-4-(2-((6-(4-(methanesulfonyl)piperazin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)-1 H -Pyrrole-2-carboxamide; (14) N,N 1-Trimethyl-4-(2-((6-(4-(trifluoromethyl)piperidin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)-1 H -Pyrrole-2-carboxamide; (15) 4-(2-((6-(4,4-difluoropiperidin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)- N,N, 1-Trimethyl-1 H -Pyrrole-2-carboxamide; (16) 4-(2-((6-(4-cyclopropylpiperazin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)- N,N, 1-Trimethyl-1 H -Pyrrole-2-carboxamide; (17) N,N 1-Trimethyl-4-(2-((6-(4-(oxecyclobutane-3-yl)piperazin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)-1 H -Pyrrole-2-carboxamide; (18) N,N 1-Trimethyl-4-(2-((6-(4-morpholinopiperidin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)-1 H -Pyrrole-2-carboxamide; (19) 4-(2-((6-(2-oxa-6-azaspiro[3.3]heptane-6-yl)pyridin-3-yl)amino)pyrimidin-4-yl)- N,N, 1-Trimethyl-1 H -Pyrrole-2-carboxamide; (20) 9-(5-((4-(5-(dimethylcarbamoyl)-1-methyl-1H-pyrrolo-3-yl)pyrimidin-2-yl)amino)pyridin-2-yl)-3,9-diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester; (21) 4-(5-((4-(5-dimethylcarbamoyl)-1-methyl-1H-pyrrolo-3-yl)pyrimidin-2-yl)amino)pyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (22) 4-(5-((4-(5-dimethylcarbamoyl)-1-methyl-1H-pyrrolo-3-yl)pyrimidin-2-yl)amino)pyridin-2-yl)-1,4-diaza-1-carboxylic acid tert-butyl ester; (23) N,N,1-Trimethyl-4-(2-((6-(4-methyl-1,4-diazacycloheptane-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carboxamide (24) 4-(2-((6-(3,9-diazaspiro[5.5]undecane-3-yl)pyridin-3-yl)amino)pyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrole-2-carboxamide (25) N,N 1-Trimethyl-4-(2-((6-(piperazin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)-1 H -Pyrrole-2-carboxamide; (26) 4-(2-((6-(1,4-diaza-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)- N,N, 1-Trimethyl-1 H -Pyrrole-2-carboxamide; (27) N,N -Diethyl-1-methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1 H -Pyrrole-2-carboxamide; (28) (1-Methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1 H -pyrrolo-2-yl)(4-methylpiperazin-1-yl) methyl ketone; (29) N -(2-(dimethylamino)ethyl)- N 1-Dimethyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1 H -Pyrrole-2-carboxamide; (30)(1-Methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1 H -pyrrolo-2-yl)(pyrrolidin-1-yl)methyl ketone; (31)(1-methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1 H -pyrrolo-2-yl)(4-methylpiperidin-1-yl)methyl ketone; (32) (4-(dimethylamino)piperidin-1-yl) (1-methyl-4-(2-((6-morpholinpyridin-3-yl)amino)pyrimidin-4-yl)-1 H -pyrrolo-2-yl)methyl ketone; (33) (4-methoxypiperidin-1-yl) (1-methyl-4-(2-((6-morpholinpyridin-3-yl)amino)pyrimidin-4-yl)-1H -pyrrolo-2-yl)methyl ketone; (34)(1-Methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1 H -pyrrolo-2-yl)(4-(methylsulfonyl)piperazin-1-yl)methyl ketone; (35)(1-Methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1 H -pyrrolo-2-yl)(4-(trifluoromethyl)piperidin-1-yl) methyl ketone; (36) (4,4-difluoropiperidin-1-yl) (1-methyl-4-(2-((6-morpholinpyridin-3-yl)amino)pyrimidin-4-yl)-1 H -pyrrolo-2-yl)methyl ketone; (37)(1-Methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1 H -pyrrolo-2-yl)(4-(oxetane-3-yl)piperazin-1-yl)methyl ketone; (38)(1-Methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1 H -pyrrolo-2-yl)(4-morpholinopiperidin-1-yl) methyl ketone; (39) (4-Methyl-1,4-diazacycloheptane-1-yl) (1-Methyl-4-(2-((6-morpholinpyridin-3-yl)amino)pyrimidin-4-yl)-1 H -pyrrolo-2-yl)methyl ketone; (40)(1-Methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1 H -pyrrolo-2-yl)(2-oxa-6-azaspiro[3.3]heptane-6-yl) methyl ketone; (41) 4-(1-methyl-4-(2-((6-morpholinpyridin-3-yl)amino)pyrimidin-4-yl)-1 H tert-butyl pyrrole-2-carbonyl)piperazine-1-carboxylate; (42) 4-(1-methyl-4-(2-((6-morpholinpyridin-3-yl)amino)pyrimidin-4-yl)-1 H tert-butyl 1,4-diaza-1-carboxylic acid (-pyrrole-2-carbonyl)-1,4-diaza-1-carboxylic acid; (43) 9-(1-methyl-4-(2-(((6-morpholinpyridin-3-yl)amino)pyrimidin-4-yl)-1 H -pyrrole-2-carbonyl)-3,9-diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester; (44)(1-Methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1 H -pyrrolo-2-yl)(piperazin-1-yl)methyl ketone; (45) (1,4-diaza-1-yl) (1-methyl-4-(2-((6-morpholinpyridin-3-yl)amino)pyrimidin-4-yl)-1 H -pyrrolo-2-yl)methyl ketone; (46)(1-Methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1 H -pyrrolo-2-yl)(3,9-diazaspiro[5.5]undecane-3-yl) methyl ketone.

[0010] The method for preparing the compounds represented by general formula I and general formula II of the present invention specifically includes the following steps: using methyl 4-bromo-1H-pyrrole-2-carboxylate as the starting material, the compounds are subjected to substitution reaction, hydrolysis reaction, amidation reaction, palladium-catalyzed CC coupling, Suzuki-Miyaura coupling, Buchwald-Hartwig coupling, and deprotection reaction to obtain the target compounds represented by general formula I and general formula II.

[0011] The above 4-(1) H 3-pyrrole-3-yl)pyrimidine compounds for breast cancer prevention can be used in the preparation of antitumor drugs.

[0012] Compared with the prior art, the beneficial effects of the present invention are as follows.

[0013] This research focuses on the design, synthesis, and evaluation of a series of novel 4-(1) compounds. H (-pyrrole-3-yl)pyrimidine compounds. This scaffold was chosen for in-depth exploration primarily due to its unique structural advantages and optimization potential. Unlike common known inhibitor nuclei, this heterocyclic system's pyrimidine ring acts as a key pharmacophore interacting with the catalytic domain, while the introduction of the pyrrole ring provides flexible modification sites for exploring allosteric regulation or fine-tuning of molecular physicochemical properties (such as solubility and membrane permeability). This invention aims to efficiently optimize the structure-activity relationship of this scaffold, significantly improving its selectivity for family enzymes while maintaining high inhibitory activity against USP7, and systematically improving the compound's pharmacokinetic properties (such as metabolic stability and blood-brain barrier penetration). Research on these compounds is expected to yield high-quality lead molecules with independent intellectual property rights, accumulate new knowledge for understanding the selective mechanisms and structure-activity relationships of USP7 inhibitors, and lay a solid chemical and biological foundation for the eventual development of USP7-targeted anti-tumor drugs suitable for clinical trials.

[0014] The preparation methods of the 4-(1H-pyrrolo-3-yl)pyrimidine compounds shown in Formula I and Formula II provided by this invention are simple, feasible, and have good yields. Detailed Implementation

[0015] The present invention will be explained in detail through the following embodiments. These embodiments are merely illustrative and do not limit the scope of the present invention in any way.

[0016] Example 1.

[0017] Preparation of intermediates 2a-2w: 2-bromo-5-nitropyridine (1 g, 4.93 mmol) was placed in a round-bottom flask with an amine derivative (7.39 mmol) and triethylamine (1.5 g, 14.78 mmol), and 20 mL of acetonitrile was added. The mixture was stirred at 65 °C for 8 h. After the reaction was completed, the mixture was quenched with water, extracted with ethyl acetate, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give a yellow solid with a yield of 75.67-95.58%.

[0018] Example 2.

[0019] Preparation of intermediate 3a-3w: Intermediate 2a-2w (0.5g) and Pd / C (0.05g) were placed in a round-bottom flask, and 20mL of tetrahydrofuran was added. The mixture was stirred at room temperature under hydrogen atmosphere for 16h. After the reaction was completed, palladium on carbon was removed by filtration, the filtrate was concentrated under reduced pressure and dried to obtain a solid with a yield of 62.32-85.56%.

[0020] Example 3.

[0021] Preparation of methyl 4-bromo-1-methyl-1H-pyrrole-2-carboxylate (5): methyl 4-bromo-1H-pyrrole-2-carboxylate (4) (5 g, 24.51 mmol) was placed in a 250 mL round-bottom flask with dimethyl sulfate (4.02 g, 31.86 mmol) and K2CO3 (6.77 g, 49.01 mmol). 100 mL of acetonitrile was added, and the mixture was stirred at 50 °C for 8 h. After the reaction was completed, the mixture was allowed to stand and then filtered. The filtrate was concentrated and dried to obtain 4.9 g of brown solid, which is methyl 4-bromo-1-methyl-1H-pyrrole-2-carboxylate, with a yield of 91.76%.

[0022] Example 4.

[0023] Preparation of 4-bromo-1-methyl-1H-pyrrole-2-carboxylic acid (6): Methyl 4-bromo-1-methyl-1H-pyrrole-2-carboxylic acid (5) (1.5 g, 6.88 mmol) and NaOH (1.1 g, 27.52 mmol) were placed in a 100 mL round-bottom flask, and 20 mL of H2O:methanol = 1:1 was added. The mixture was reacted at 65 °C for 4 h. After the reaction was completed, the mixture was cooled to room temperature, and methanol was removed by vacuum. At the same time, 50 mL of H2O was added, and the pH was adjusted to 5 with 1 mol / L dilute hydrochloric acid. A large amount of white solid precipitated out. After standing, the solid was filtered and dried to obtain 0.76 g of white solid, which is 4-bromo-1-methyl-1H-pyrrole-2-carboxylic acid, with a yield of 54.29%.

[0024] Example 5.

[0025] Preparation of 4-bromo-N,N,1-trimethyl-1H-pyrrole-2-carboxamide (7): 4-bromo-1-methyl-1H-pyrrole-2-carboxylic acid (6) (1 g, 4.90 mmol) was placed in a round-bottom flask with HATU (2.05 g, 5.39 mmol) and triethylamine (1.49 g, 14.7 mmol) in acetonitrile as solvent and activated at 0 °C for 1 h. After activation, dimethylamine (30% methanol solution) (0.81 g, 5.39 mmol) was added and reacted at room temperature for 16 h. After the reaction was completed, the solvent was removed under reduced pressure, dried, and purified by acidic silica gel column chromatography. The mobile phase system was petroleum ether (PE): ethyl acetate (EA) = 5:1, yielding 0.65 g of yellow solid, namely 4-bromo-N,N,1-trimethyl-1H-pyrrole-2-carboxamide, with a yield of 57.52%.

[0026] Example 6.

[0027] Preparation of N,N,1-trimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)-1H-pyrrole-2-carboxamide (8): 4-bromo-N,N,1-trimethyl-1H-pyrrole-2-carboxamide (7) (0.5 g, 2.16 mmol) was mixed with bis(pinacolyl)diboron (1.65 g, 6.49 mmol), CH3COOK (0.64 g, 6.49 mmol), and bis(tricyclohexylphosphine)palladium dichloride (0.22 g, 2.16 mmol). (302.91 μmol) was placed in a round-bottom flask, and about 20 ml of DMSO solvent was added. The mixture was heated to 90 °C under nitrogen protection and stirred for 9 h. After the reaction was completed, the palladium catalyst was removed by filtration with diatomaceous earth, water was added and allowed to stand, and the mixture was extracted with ethyl acetate, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give 0.21 g of crude product, namely N,N,1-trimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)-1H-pyrrole-2-carboxamide, with a yield of 44.12%.

[0028] Example 7.

[0029] Preparation of 4-(2-chloropyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrole-2-carboxamide (9): N,N,1-trimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)-1H-pyrrole-2-carboxamide (8) (1 g, 3.60 mmol) was placed in a 100 ml flask with 2,4-dichloropyrimidin (0.8 g, 5.39 mmol), Na2CO3 (0.76 g, 7.19 mmol), and [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (0.21 g, 287.61 μmol), and 30 ml of [aluminum chloride] was added. The reaction mixture of 1,4-dioxane and H₂O in a 5:1 ratio was heated to 80°C and stirred for 16 h under nitrogen protection. After the reaction was complete, the palladium catalyst was removed by filtration with diatomaceous earth. The filtrate was extracted with ethyl acetate, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by acidic silica gel column chromatography with a mobile phase of petroleum ether (PE):ethyl acetate (EA) in a 1:1 ratio. 0.65 g of a brown solid, 4-(2-chloropyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrole-2-carboxamide, was obtained, with a yield of 68.42%. 1 H NMR (400 MHz, DMSO- d 6) δ8.55 (d, J = 5.3 Hz, 1H), 7.86 (d, J = 1.8 Hz, 1H), 7.68 (d, J = 5.3 Hz, 1H), 7.05(d, J = 1.8 Hz, 1H), 3.72 (s, 3H), 3.06 (s, 6H). 13 C NMR (101 MHz, DMSO- D 6) δ163.99, 162.63, 160.92, 160.24, 129.01,128.24, 119.36, 114.85, 111.40, 36.38,25.48. LC-MS: m / z: calculated for C 12 H 13 ClN4O ([M+H) + ):265.0778, find:265.0807.

[0030] Example 8.

[0031] Preparation of 4-bromo-1-methyl-1H-pyrrole-2-carboxylic acid benzyl ester (12): 4-bromo-1-methyl-1H-pyrrole-2-carboxylic acid (6) (0.5 g, 2.45 mmol) was placed in a round-bottom flask with (bromomethyl)benzene (0.42 g, 2.45 mmol) and K2CO3 (0.34 g, 2.45 mmol). About 25 mL of DMF solvent was added, and the mixture was stirred at room temperature for 2 h. After the reaction was completed, the reaction was quenched with water, extracted with ethyl acetate, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give 0.55 g of gray solid, with a yield of 76.39%.

[0032] Example 9.

[0033] Preparation of 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborin-2-yl)-1H-pyrrole-2-carboxylate (13): 4-bromo-1-methyl-1H-pyrrole-2-carboxylate (12) (1 g, 3.40 mmol) was placed in a round-bottom flask with bis(pinacol)diboron (2.59 g, 10.20 mmol), CH3COOK (1 g, 10.20 mmol), and bis(tricyclohexylphosphine)palladium dichloride (0.16 g, 237.98 μmol). About 20 ml of DMSO solvent was added, and the mixture was heated to 90 °C under nitrogen protection and stirred for 9 h. After the reaction was completed, the palladium catalyst was removed by filtration with diatomaceous earth, water was added and allowed to stand, and the mixture was extracted with ethyl acetate, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 0.62 g of crude product, with a yield of 53.44%.

[0034] Example 10.

[0035] Preparation of 4-(2-chloropyrimidin-4-yl)-1-methyl-1H-pyrrole-2-carboxylic acid benzyl ester (14): 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)-1H-pyrrole-2-carboxylic acid benzyl ester (13) (0.5 g, 1.47 mmol) was placed in a round-bottom flask with 2,4-dichloropyrimidin (0.33 g, 2.20 mmol), Na2CO3 (0.31 g, 2.93 mmol), and [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (0.11 g, 146.54 μmol), and 30 ml of [dichloropyrimidin-4-yl)-1-methyl-1H-pyrrole-2-carboxylic acid benzyl ester (13) (0.5 g, 1.47 mmol), 2,4-dichloropyrimidin (0.33 g, 2.20 mmol), Na2CO3 (0.31 g, 2.93 mmol), and [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (0.11 g, 146.54 μmol). 1,4-Dioxane:H₂O = 5:1 was reacted at 80°C under nitrogen protection with stirring for 16 h. After the reaction was complete, the palladium catalyst was removed by diatomaceous earth filtration. The filtrate was extracted with ethyl acetate, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by acidic silica gel column chromatography with a mobile phase of petroleum ether (PE):ethyl acetate (EA) = 10:1, yielding 0.33 g of a white solid, with a yield of 68.75%. 1 H NMR (400MHz, DMSO- d6) δ 8.57 (d, J = 5.3 Hz, 1H), 8.04 (d, J = 2.0 Hz, 1H), 7.79 (d, J =5.3 Hz, 1H), 7.55 (d, J = 2.0 Hz, 1H), 7.47 – 7.43 (m, 2H), 7.42 – 7.32 (m, 3H), 5.28 (s, 2H), 3.92 (s, 3H). 13 C NMR (101 MHz, DMSO- D 6) δ 163.29, 160.90,160.59, 160.34, 136.75, 132.53, 129.06, 128.62, 128.50, 124.22, 120.22,116.76, 115.14, 65.91, 37.65.LC-MS: m / z:calculated for C 17 H 14 ClN3O2([M+H) + ):328.0775, found: 328.1115.

[0036] Example 11.

[0037] Preparation of 1-methyl-4-(2-(((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid benzyl ester (15): 4-(2-chloropyrimidin-4-yl)-1-methyl-1H-pyrrole-2-carboxylic acid benzyl ester (14) (1 g, 3.05 mmol) was mixed with 6-morpholinopyridin-3-amine (3e) (0.66 g, 3.66 mmol), Cs2CO3 (1.99 g, 6.10 mmol), and 4,5-bisdiphenylphosphine-9,9-dimethyloxanthracene (0.5 g, 0.5 mmol). 3 g (915.28 μmol) and tris(dibenzylacetone)palladium (0.42 g (457.64 μmol)) were placed in a round-bottom flask, and about 30 mL of 1,4-dioxane solvent was added. The mixture was heated to 100 °C and stirred for 16 h under nitrogen protection. After the reaction was completed, the palladium catalyst was removed by filtration with diatomaceous earth. The filtrate was concentrated under reduced pressure and purified by acidic silica gel column chromatography with a mobile phase of petroleum ether (PE):ethyl acetate (EA) = 2:1. 0.7 g of grayish-white solid was obtained, with a yield of 48.61%. 1 H NMR (400 MHz, DMSO-) d 6) δ 9.23 (s, 1H), 8.49 (d, J= 2.7 Hz, 1H), 8.29 (d, J = 5.2 Hz,1H), 7.99 – 7.94 (m, 1H), 7.86 (d, J = 2.1 Hz, 1H), 7.48 – 7.36 (m, 6H), 7.04(d, J = 5.2 Hz, 1H), 6.80 (d, J = 9.1 Hz, 1H), 5.28 (s, 2H), 3.94 (s, 3H), 3.69 (s, 4H), 3.34 (s, 4H). 13 C NMR (101 MHz, DMSO- D 6) δ 160.78, 160.50, 160.45,158.60, 155.44, 139.47, 136.84, 131.28, 130.34, 129.58, 129.06, 128.61,128.54, 123.49, 122.25, 116.41, 107.33, 107.04, 66.52, 65.82, 46.44,37.54.LC-MS: m / z: calculated forC 26 H 26 N6O3([M+H)) + ): 471.2066, found: 471.2169.

[0038] Example 12.

[0039] Preparation of 1-methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (16): 1-methyl-4-(2-(((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid benzyl ester (15) (0.5 g) and Pd / C (0.05 g) were placed in a round-bottom flask, and about 20 mL of tetrahydrofuran (THF) solvent was added. The mixture was stirred at room temperature under hydrogen atmosphere for 12 h. After the reaction was completed, palladium on carbon was removed by filtration, the filtrate was concentrated under reduced pressure and dried to obtain 0.2 g of green solid, with a yield of 50.00%. 1 HNMR (400 MHz, DMSO- d 6) δ 9.21 (s, 1H), 8.50 (d, J = 2.7 Hz, 1H), 8.28 (d, J = 5.2Hz, 1H), 7.97 (dd, J= 9.1, 2.7 Hz, 1H), 7.76 (d, J = 1.9 Hz, 1H), 7.35 (d, J = 2.0Hz, 1H), 7.00 (d, J = 5.2 Hz, 1H), 6.83 (d, J = 9.1 Hz, 1H), 3.90 (s, 3H), 3.71 –3.68 (m, 4H), 3.34 (s, 4H). 13 C NMR (101 MHz, DMSO- D 6) δ 162.56, 162.47, 160.77,158.57, 155.43, 139.38, 130.55, 130.30, 129.63, 124.95, 121.82, 115.89,107.42, 106.96, 66.53, 46.45, 37.51. LC-MS: m / z: calculated forC 19 H 20 N6O3([M+H)) + ): 381.1597, found: 381.2890.

[0040] Example 13.

[0041] The compounds represented by general formulas I and II were synthesized by the following method.

[0042] (1) Preparation of 4-(2-((6-(dimethylamino)pyridin-3-yl)amino)pyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrole-2-carboxamide (10a): 4-(2-chloropyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrole-2-carboxamide (9) (0.2 g, 755.54 μmol) was reacted with N 2 N 2Dimethylpyridine-2,5-diamine (3a) (0.12 g, 906.64 μmol), Cs₂CO₃ (0.49 g, 1.51 mmol), 4,5-bis(diphenylphosphine-9,9-dimethyloxanthracene) (0.13 g, 226.66 μmol), and tris(dibenzylacetone)dipalladium (0.10 g, 113.33 μmol) were placed in a round-bottom flask, and about 30 mL of 1,4-dioxane solvent was added. The mixture was heated to 100 °C under nitrogen protection and stirred for 16 h. After the reaction was completed, the palladium catalyst was removed by filtration with diatomaceous earth. The filtrate was concentrated under reduced pressure and purified by acidic silica gel column chromatography with dichloromethane (DCM):methanol (MeOH) = 60:1 as the mobile phase, yielding 0.07 g of a pink solid, with a yield of 25.36%. 1 H NMR (400 MHz, DMSO-d6) δ 9.05 (s, 1H), 8.38 (s,1H), 8.24 (s, 1H), 7.92 (d, J = 8.9 Hz, 1H), 7.63 (s, 1H), 6.94 (s, 2H), 6.64(d, J = 9.8 Hz, 1H), 3.72 (s, 3H), 3.06 (s, 6H), 2.97 (s, 6H). 13 C NMR (101 MHz, DMSO-D6) δ 162.94, 161.10, 160.89, 158.26, 155.53,139.62, 130.87, 127.69,127.40, 127.35, 121.33, 111.12, 106.70, 105.98, 38.65, 36.25. LC-MS: m / z:calculated for C 19 H 23 N7O ([M+H)) + ):366.1964, find: 366.2577.

[0043] (2) Preparation of 4-(2-((6-(diethylamino)pyridin-3-yl)amino)pyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrole-2-carboxamide (10b): using 4-(2-chloropyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrole-2-carboxamide (9) and N 2 N 2 Using diethylpyridine-2,5-diamine (3b) as the raw material, the preparation method was the same as in 10a, yielding 0.12 g of red solid with a yield of 40.40%. 1H NMR (400 MHz, DMSO-d6) δ 8.98 (s, 1H), 8.31 (d, J = 2.7 Hz, 1H), 8.23 ​​(d, J = 5.2 Hz, 1H), 7.85 (dd, J = 9.0, 2.6 Hz,1H), 7.63 (d, J = 1.9 Hz,1H), 6.96 – 6.92 (m, 2H), 6.56 (d, J = 9.1 Hz, 1H), 3.73 (s, 3H), 3.45 (q, J= 7.0 Hz, 4H), 3.06(s, 6H), 1.09 (t, J = 7.0 Hz, 6H). 13 C NMR (101 MHz, DMSO-D6) δ 162.96, 161.13, 161.07, 158.24, 153.59,140.52, 131.34, 127.38, 127.34,121.41, 111.18, 106.58, 105.22, 42.37, 36.28, 13.47. LC-MS: m / z: calculatedfor C 21 H 27 N7O ([M+H)) + ):394.2277, find: 394.2666.

[0044] (3) Preparation of N,N,1-trimethyl-4-(2-((6-(pyrrolidin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carboxamide (10c): Using 4-(2-chloropyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrole-2-carboxamide (9) and 6-(pyrrolidin-1-yl)pyridin-3-amine (3c) as raw materials, the preparation method is the same as in 10a, and 0.10 g of brownish-red solid is obtained with a yield of 33.89%. 1 H NMR (400 MHz, DMSO-d6) δ 8.99 (s, 1H), 8.34 (s, 1H), 8.23 ​​(d, J =5.2 Hz, 1H), 7.88 (d, J = 7.5 Hz, 1H), 7.62 (s, 1H), 6.94 (s, 2H), 6.43 (d, J = 8.7 Hz, 1H), 3.72 (s, 3H), 3.39 – 3.34 (m, 4H), 3.06 (s, 6H), 1.93 (d, J =6.5 Hz, 4H). 13C NMR (101 MHz, DMSO-D6) δ 162.99, 161.11, 160.99, 158.27,153.75,140.44, 131.03, 127.40, 127.32, 127.16, 121.38, 111.13, 106.58,106.10, 47.10, 36.26, 25.57. LC-MS: m / z: calculated for C 21 H 25 N7O ([M+H)) + ):392.2121, find: 392.2301.

[0045] (4) Preparation of 4-(2-((6-((2-(dimethylamino)ethyl)(methyl)amino)pyridin-3-yl)amino)pyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrole-2-carboxamide (10d): with 4-(2-chloropyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrole-2-carboxamide (9) and N 2 -(2-(dimethylamino)ethyl)-N 2 Using 2,5-methylpyridine-2,5-diamine (3d) as the raw material, the preparation method was the same as in 10a, yielding 0.12 g of red solid with a yield of 37.62%. 1 H NMR (400 MHz, DMSO-d6) δ 9.01 (s,1H), 8.34 (d, J = 2.7 Hz, 1H), 8.24 (d, J = 5.2 Hz, 1H), 7.88 (dd, J = 9.1,2.8 Hz, 1H), 7.63 (d, J = 1.8 Hz, 1H), 6.94 (dd, J= 3.6, 1.7 Hz, 2H), 6.58(d, J = 9.1 Hz, 1H), 3.72 (s, 3H), 3.57 (t, J = 7.0 Hz, 2H), 3.06 (s, 6H), 2.96 (s, 3H), 2.37 (t, J = 7.0 Hz, 2H), 2.17 (s, 6H). 13C NMR (101 MHz, DMSO-D6) δ 162.96, 161.13, 160.99, 158.26, 154.63, 140.18, 131.08, 127.39, 127.35,127.28,121.38, 111.17, 106.65, 105.34, 56.79, 47.99, 46.07, 36.92, 36.29. LC-MS: m / z: calculated for C 22 H 30 N8O ([M+H)) + ):423.2543, find: 423.2960.

[0046] (5) Preparation of N,N,1-trimethyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carboxamide (10e): Using 4-(2-chloropyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrole-2-carboxamide (9) and 6-morpholinopyridin-3-amine (3e) as raw materials, the preparation method is the same as in 10a, and 0.20 g of pale yellow solid is obtained with a yield of 64.94%. 1 H NMR(400 MHz, DMSO-d6) δ 9.16 (s, 1H), 8.45 (d, J = 2.3 Hz, 1H), 8.24 (d, J = 5.2Hz, 1H), 7.98 (dd, J = 9.1, 2.7 Hz, 1H), 7.61 (d, J = 1.8 Hz, 1H), 6.96 –6.91 (m, 2H), 6.80 (d, J = 9.0 Hz, 1H), 3.70 (s, 3H), 3.68 – 3.65 (m, 4H), 3.31 (d, J = 4.8 Hz, 4H), 3.03 (s, 6H). 13 C NMR (101 MHz, DMSO-D6) δ 162.95,161.18, 160.76, 158.30, 155.40, 139.38, 130.23, 129.74, 127.48, 127.39,121.32, 111.13, 107.38, 106.97, 66.53, 46.47, 36.29.LC-MS: m / z: calculatedfor C 21 H 25 N7O2([M+H) +):408.2070, find: 408.2180.

[0047] (6) Preparation of N,N,1-trimethyl-4-(2-((6-thiomorpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carboxamide (10f): Using 4-(2-chloropyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrole-2-carboxamide (9) and 6-thiomorpholinopyridin-3-amine (3f) as raw materials, the preparation method is the same as in 10a, and 0.11 g of wine-red solid is obtained with a yield of 34.38%. 1 HNMR (400 MHz, DMSO-d6) δ 9.15 (s, 1H), 8.44 (d, J = 2.7 Hz, 1H), 8.26 (d, J =5.2 Hz, 1H), 7.97 (d, J = 11.6 Hz, 1H), 7.64 (s, 1H), 6.99 – 6.93 (m, 2H),6.83 (d, J = 9.0 Hz, 1H), 3.84 – 3.79 (m, 4H), 3.73 (s, 3H), 3.06 (s, 6H),2.61 – 2.57 (m, 4H). 13 C NMR (101 MHz, DMSO-D6) δ 162.95, 161.17, 160.80,158.30, 154.21,139.66, 130.70, 128.83, 127.45, 127.40, 121.32, 111.14,107.74, 106.91, 48.28, 36.30, 25.57. LC-MS: m / z: calculated for C 21 H 25 N7OS ([M+H)) + ):424.1841, find: 424.2043.

[0048] (7) Preparation of N,N,1-trimethyl-4-(2-((6-(4-methylpiperazin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carboxamide (10 g): Using 4-(2-chloropyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrole-2-carboxamide (9) and 6-(4-methylpiperazin-1-yl)pyridin-3-amine (3 g) as raw materials, the preparation method is the same as in 10a, and 0.13 g of yellow solid is obtained, with a yield of 41.01%. 1H NMR (400 MHz, DMSO-d6) δ 9.15 (s, 1H), 8.44 (d, J = 2.7Hz, 1H), 8.26 (d, J = 5.2 Hz, 1H), 7.96 (dd, J = 9.2, 2.7 Hz, 1H), 7.63 (d, J= 1.8 Hz, 1H), 6.98 – 6.93 (m, 2H), 6.81 (d, J = 8.9 Hz, 1H), 3.72 (s, 3H), 3.39 – 3.35 (m, 4H), 3.05 (s, 6H), 2.38 (t, J = 5.1 Hz, 4H), 2.19 (s, 3H). 13 CNMR (101 MHz, DMSO-D6) δ 162.95, 161.17, 160.79, 158.29, 155.39, 139.45,130.30, 129.25, 127.47, 127.37, 121.33, 111.12, 107.42, 106.91, 54.99, 46.41,45.91,36.29. LC-MS: m / z: calculated for C 22 H 28 N8O ([M+H)) + ):421.2386, find:421.2481.

[0049] (8) Preparation of N,N,1-trimethyl-4-(2-((6-(4-methylpiperidin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carboxamide (10h): Using 4-(2-chloropyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrole-2-carboxamide (9) and 6-(4-methylpiperidin-1-yl)pyridin-3-amine (3h) as raw materials, the preparation method is the same as in 10a, and 0.16 g of yellow solid is obtained, with a yield of 50.63%. 1H NMR (400 MHz, DMSO-d6) δ 9.11 (s, 1H), 8.41 (d, J = 2.8Hz, 1H), 8.26 (d, J = 5.2 Hz, 1H), 7.93 (dd, J = 9.1, 2.8Hz, 1H), 7.64 (d, J= 1.8 Hz, 1H), 6.95 (dd, J = 6.3, 3.5 Hz, 2H), 6.80 (d, J = 9.1 Hz, 1H), 4.15(d, J = 13.1 Hz, 2H), 3.73 (s,3H), 3.06 (s, 6H), 2.69 (t, J = 12.5 Hz, 2H),1.64 (d, J = 9.7 Hz, 2H), 1.54 (dq, J = 7.3, 3.7, 3.3 Hz, 1H), 1.15 – 1.07(m,2H), 0.91 (d, J = 6.5 Hz, 3H). 13 C NMR (101 MHz, DMSO-D6) δ 162.95, 161.15,160.84, 158.27, 155.43,139.63, 130.52, 128.56, 127.44, 127.36, 121.34,111.13, 107.34, 106.81, 46.25, 36.28, 33.79, 31.15, 22.44. LC-MS: m / z:calculated for C 23 H 29 N7O ([M+H)) + ):420.2434, find: 420.2519.

[0050] (9) Preparation of 4-(2-((6-(4-(dimethylamino)piperidin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrole-2-carboxamide (10i): Using 4-(2-chloropyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrole-2-carboxamide (9) and 6-(4-(dimethylamino)piperidin-1-yl)pyridin-3-amine (3i) as raw materials, the preparation method is the same as in 10a, and 0.12 g of yellow solid is obtained, with a yield of 35.50%. 1H NMR (400 MHz, DMSO-d6) δ 9.12 (s, 1H), 8.42 (d, J= 2.7 Hz, 1H), 8.26 (d, J = 5.2 Hz, 1H), 7.95 (dd, J = 9.0, 2.7 Hz,1H), 7.64(d, J = 1.8 Hz, 1H), 6.95 (dd, J = 7.9, 3.5 Hz, 2H), 6.83 (d, J = 9.1 Hz,1H), 4.18 (d, J = 12.1 Hz, 2H), 3.73 (s, 3H), 3.06 (s, 6H), 2.72 (t, J =11.7Hz, 2H), 2.29 – 2.20 (m, 1H), 2.17 (s, 6H), 1.79 (d, J = 11.9 Hz, 2H), 1.35 (qd, J = 11.8, 3.8 Hz, 2H). 13 C NMR (101 MHz, DMSO-D6) δ 162.99, 161.16,160.80, 158.31, 155.13, 139.58, 130.55, 128.80, 127.45, 127.38,121.31,111.13, 107.52, 106.87, 62.41, 45.31, 41.57, 36.27, 27.68. LC-MS: m / z:calculated for C 24 H 32 N8O ([M+H)) + ):449.2699, find: 449.2990.

[0051] (10) Preparation of 4-(2-((6-(4-isopropylpiperazin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrole-2-carboxamide (10j): Using 4-(2-chloropyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrole-2-carboxamide (9) and 6-(4-isopropylpiperazin-1-yl)pyridin-3-amine (3j) as raw materials, the preparation method is the same as in 10a, and 0.14 g of yellow solid is obtained, with a yield of 41.42%. 1H NMR (400 MHz, DMSO-d6) δ 9.15 (s, 1H), 8.44 (d, J = 2.7Hz, 1H), 8.27 (d, J = 5.2 Hz, 1H), 7.97 (dd, J = 9.1, 2.8 Hz,1H), 7.65 (d, J= 1.8 Hz, 1H), 6.99 – 6.94 (m, 2H), 6.81 (d, J = 9.1 Hz, 1H), 3.73 (s, 3H), 3.37 (d, J = 5.6 Hz, 4H), 3.07(s, 6H), 2.66 (p, J = 6.5 Hz, 1H), 2.52 (t, J =5.1 Hz, 4H), 0.99 (d, J = 6.5 Hz, 6H). 13 C NMR (101 MHz, DMSO-D6) δ 162.95,161.17, 160.81, 158.29, 155.49, 139.52, 130.34, 129.17, 127.47, 127.37,121.34, 111.13, 107.32, 106.89, 54.27, 48.46, 46.41,36.39, 36.29, 18.75. LC-MS: m / z: calculated for C 24 H 32 N8O ([M+H)) + ):449.2699, find: 449.2523.

[0052] (11) Preparation of 4-(2-((6-(4-ethylpiperazin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrole-2-carboxamide (10k): Using 4-(2-chloropyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrole-2-carboxamide (9) and 6-(4-ethylpiperazin-1-yl)pyridin-3-amine (3k) as raw materials, the preparation method is the same as in 10a, and 0.15 g of yellow solid is obtained, with a yield of 45.73%. 1H NMR (400 MHz, DMSO-d6) δ 9.15 (s, 1H), 8.44 (d, J = 2.7Hz, 1H), 8.26 (d, J = 5.2 Hz, 1H), 7.97 (dd, J = 9.1, 2.7 Hz,1H), 7.64 (d, J= 1.8 Hz, 1H), 6.98 – 6.93 (m, 2H), 6.82 (d, J = 9.1 Hz, 1H), 3.72 (s, 3H), 3.38 (d, J = 5.2 Hz, 4H), 3.06(s, 6H), 2.46 (t, J = 4.9 Hz, 4H), 2.36 (q, J =7.2 Hz, 2H), 1.02 (t, J = 7.2 Hz, 3H). 13 C NMR (101 MHz, DMSO-D6) δ 162.95,161.17, 160.79, 158.30, 155.40, 139.46, 130.32, 129.27, 127.47, 127.38,121.33, 111.13, 107.41, 106.91, 52.70, 52.23, 45.96,36.29, 12.47. LC-MS: m / z:calculated for C 23 H 30 N8O ([M+H)) + ):435.2543, find: 435.2686.

[0053] (12) Preparation of 4-(2-((6-(4-methoxypiperidin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrole-2-carboxamide (10l): Using 4-(2-chloropyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrole-2-carboxamide (9) and 6-(4-methoxypiperidin-1-yl)pyridin-3-amine (3l) as raw materials, the preparation method is the same as in 10a, and 0.12 g of red solid is obtained, with a yield of 36.47%. 1H NMR (400 MHz, DMSO-d6) δ 9.13 (s, 1H), 8.42 (s, 1H), 8.26 (d, J = 5.2 Hz, 1H), 7.95 (d, J = 10.1 Hz, 1H), 7.64 (s,1H), 7.00 – 6.93(m, 2H), 6.83 (d, J = 8.9 Hz, 1H), 3.91 – 3.82 (m, 2H), 3.73 (s, 3H), 3.39 –3.35 (m, 1H), 3.25 (s, 3H), 3.05 (d, J = 11.1 Hz, 8H),1.88 (d, J = 8.5 Hz,2H), 1.42 (d, J = 7.6 Hz, 2H). 13 C NMR (101 MHz, DMSO-D6) δ 162.95, 161.16,160.82, 158.27, 155.11, 139.59, 130.50, 128.79, 127.45, 127.36, 121.34,111.13,107.42, 106.85, 76.41, 55.36, 43.71, 36.28, 30.48. LC-MS: m / z:calculated for C 23 H 29 N7O2([M+H) + ):436.2383, find: 436.2816.

[0054] (13) Preparation of N,N,1-trimethyl-4-(2-((6-(4-(methanesulfonyl)piperazin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carboxamide (10m): Using 4-(2-chloropyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrole-2-carboxamide (9) and 6-(4-(methanesulfonyl)piperazin-1-yl)pyridin-3-amine (3m) as raw materials, the preparation method is the same as in 10a, and 0.18 g of yellow solid was obtained, with a yield of 49.18%. 1H NMR (400 MHz, DMSO-d6) δ 9.22 (s, 1H), 8.50 (d, J = 2.7 Hz, 1H), 8.29 (d, J = 5.2 Hz, 1H), 8.04 (dd, J = 9.1, 2.7Hz, 1H), 7.66 (d, J = 1.8 Hz, 1H), 7.00 (d, J =5.2 Hz, 1H), 6.96 (d, J = 1.8Hz, 1H), 6.91 (d, J = 9.1 Hz, 1H), 3.74 (s, 3H), 3.56 – 3.51 (m, 4H), 3.21(t, J = 5.1 Hz, 4H),3.08 (s, 6H), 2.91 (s, 3H). 13 C NMR (101 MHz, DMSO-D6) δ162.95, 161.19, 160.74, 158.31, 154.61, 139.35, 130.35, 129.83, 127.50,127.39, 121.30, 111.12, 107.92, 107.02, 45.64, 36.30, 34.27.LC-MS: m / z:calculated for C 22 H 28 N8O3S ([M+H) + ):485.2005, find: 485.2079.

[0055] (14) Preparation of N,N,1-trimethyl-4-(2-((6-(4-(trifluoromethyl)piperidin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carboxamide (10n): Using 4-(2-chloropyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrole-2-carboxamide (9) and 6-(4-(trifluoromethyl)piperidin-1-yl)pyridin-3-amine (3n) as raw materials, the preparation method is the same as in 10a, and 0.14 g of brownish-yellow solid is obtained, with a yield of 39.22%. 1H NMR (400 MHz, DMSO-d6) δ 9.16 (s, 1H), 8.45 (d,J = 2.8 Hz, 1H), 8.27 (d, J = 5.2 Hz, 1H), 7.98 (dd, J = 9.1, 2.7 Hz, 1H), 7.64 (d, J = 1.8 Hz, 1H), 6.97 (d, J =5.2 Hz, 1H), 6.95 (d, J = 1.8 Hz, 1H), 6.87 (d, J = 9.2 Hz, 1H), 4.29 (d, J = 12.7 Hz, 2H), 3.73 (s, 3H), 3.06 (s,6H), 2.76 (td, J = 12.8, 2.5 Hz, 2H), 2.59– 2.52 (m, 1H), 1.84 (d, J = 10.2Hz, 2H), 1.44 (tt, J = 12.5, 6.2 Hz, 2H). 13 C NMR (101 MHz, DMSO-D6) δ 162.95,161.18, 160.80, 158.29, 154.84,139.54, 130.49, 129.70, 129.19, 127.47,127.38, 126.93, 121.33, 111.13, 107.71, 106.92, 44.82, 36.28, 23.96. LC-MS:m / z: calculated for C 23 H 26 F3N7O ([M+H) + ):474.2151, find: 474.2698.

[0056] (15) Preparation of 4-(2-((6-(4,4-difluoropiperidin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrole-2-carboxamide (10o): Using 4-(2-chloropyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrole-2-carboxamide (9) and 6-(4,4-difluoropiperidin-1-yl)pyridin-3-amine (3o) as raw materials, the preparation method is the same as in 10a, and 0.13 g of brownish-yellow solid is obtained, with a yield of 36.42%. 1H NMR (400 MHz, DMSO-d6) δ 9.20 (s, 1H), 8.48 (d, J = 2.7Hz, 1H), 8.27 (d, J = 5.2 Hz, 1H), 8.01 (dd, J = 9.1, 2.7 Hz,1H), 7.65 (d, J= 1.8 Hz, 1H), 6.98 (d, J = 5.2 Hz, 1H), 6.97 – 6.93 (m, 2H), 3.73 (s, 3H), 3.63 – 3.59 (m, 4H), 3.07 (s, 6H), 2.02 – 1.93 (m, 4H). 13 C NMR (101 MHz, DMSO-D6) δ 162.94, 161.19, 160.75, 158.30, 153.92,139.43, 130.53, 129.55, 127.48,127.40, 123.74, 121.30, 111.13, 107.90, 107.00, 43.22, 43.17, 43.12, 36.30,33.42, 33.20, 32.98. LC-MS: m / z: calculated for C 22 H 25 F2N7O ([M+H) + ):442.2089,find: 442.2188.

[0057] (16) Preparation of 4-(2-((6-(4-cyclopropylpiperazin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrole-2-carboxamide (10p): Using 4-(2-chloropyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrole-2-carboxamide (9) and 6-(4-cyclopropylpiperazin-1-yl)pyridin-3-amine (3p) as raw materials, the preparation method is the same as in 10a, and 0.14 g of yellow solid is obtained, with a yield of 41.54%. 1H NMR (400 MHz, DMSO-d6) δ 9.12 (s, 1H), 8.41 (d, J = 2.7Hz, 1H), 8.23 ​​(d, J = 5.2 Hz, 1H), 7.94 (dd, J = 9.0, 2.8 Hz,1H), 7.61 (d, J= 1.9 Hz, 1H), 6.94 – 6.91 (m, 2H), 6.78 (d, J = 9.2 Hz, 1H), 3.69 (s, 3H), 3.31 (s, 4H), 3.03 (s, 6H), 2.58 (t, J = 5.0 Hz, 4H), 1.59 (dt, J = 6.5, 3.0Hz, 1H), 0.41 – 0.36 (m, 2H), 0.31 (d, J = 3.3 Hz, 2H). 13 C NMR (101 MHz, DMSO-D6) δ 162.95, 161.17, 160.80, 158.29, 155.37, 139.48, 130.34, 129.22, 127.46,127.37,121.34, 111.13, 107.38, 106.90, 53.14, 45.97, 38.70, 36.29, 6.15. LC-MS: m / z: calculated for C 24 H 30 N8O ([M+H)) + ):447.2543, find: 447.2991.

[0058] (17) Preparation of N,N,1-trimethyl-4-(2-((6-(4-(oxecyclobutan-3-yl)piperazin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carboxamide (10q): Using 4-(2-chloropyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrole-2-carboxamide (9) and 6-(4-(oxecyclobutan-3-yl)piperazin-1-yl)pyridin-3-amine (3q) as raw materials, the preparation method was the same as in 10a, yielding 0.11 g of a yellow solid. Yield: 31.52%. 1H NMR (400 MHz, DMSO-d6) δ 9.17 (s,1H), 8.46 (d, J = 2.7 Hz, 1H), 8.27 (d, J = 5.2 Hz, 1H), 7.99 (dd, J = 9.1,2.7 Hz, 1H), 7.64 (d, J = 1.7 Hz, 1H), 6.99 – 6.94 (m, 2H), 6.83 (d, J = 9.1Hz, 1H), 4.55 (t, J = 6.5Hz, 2H), 4.46 (t, J = 6.0 Hz, 2H), 3.73 (s, 3H), 3.41 (t, J = 5.0 Hz, 5H), 3.07 (s, 6H), 2.34 (t, J = 5.0 Hz, 4H). 13 C NMR (101MHz, DMSO-D6) δ 162.95, 161.18, 160.79, 158.30, 155.29,139.45, 130.32,129.35, 127.48, 127.37, 121.33, 111.13, 107.43, 106.92, 74.94, 59.06, 49.42,45.71, 36.29. LC-MS: m / z: calculated for C 24 H 30 N8O2([M+H)) + ):463.2492, find:463.2949.

[0059] (18) Preparation of N,N,1-trimethyl-4-(2-((6-(4-morpholinopiperidin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carboxamide (10r): Using 4-(2-chloropyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrole-2-carboxamide (9) and 6-(4-morpholinopiperidin-1-yl)pyridin-3-amine (3r) as raw materials, the preparation method is the same as in 10a, and 0.09 g of red solid is obtained, with a yield of 24.32%. 1H NMR (400 MHz, DMSO-d6) δ 9.13 (s, 1H), 8.42 (d, J = 2.7Hz, 1H), 8.26 (d, J = 5.2 Hz, 1H), 7.95 (dd, J = 9.0, 2.8 Hz, 1H), 7.64 (d, J= 1.8 Hz, 1H), 6.97 – 6.94 (m, 2H), 6.82 (d, J = 9.1 Hz, 1H), 4.19 (d, J =13.0 Hz, 2H), 3.73 (s, 3H), 3.55 (t, J = 4.5 Hz, 4H), 3.06 (s, 6H), 2.71 (td,J = 12.5, 2.4 Hz, 2H), 2.46 (d, J = 4.6 Hz, 4H), 2.36 – 2.28 (m, 1H), 1.85 –1.79(m, 2H), 1.41 – 1.32 (m, 2H). 13 C NMR (101 MHz, DMSO-D6) δ 162.95, 161.17,160.82, 158.28, 155.20, 139.58, 130.45, 128.81, 127.45, 127.37, 121.34,111.14,107.44, 106.85, 67.07, 62.00, 49.96, 45.43, 36.29, 27.88. LC-MS: m / z:calculated for C 26 H 34 N8O2([M+H)) + ):491.2805, find: 491.3403.

[0060] (19) Preparation of 4-(2-((6-(2-oxa-6-azaspiro[3.3]heptane-6-yl)pyridin-3-yl)amino)pyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrole-2-carboxamide (10s): Using 4-(2-chloropyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrole-2-carboxamide (9) and 6-(2-oxa-6-azaspiro[3.3]heptane-6-yl)pyridin-3-amine (3s) as raw materials, the preparation method is the same as in 10a, and 0.08 g of red solid is obtained, with a yield of 25.81%. 1H NMR (400 MHz, DMSO-d6) δ 9.13(s, 1H), 8.40 (d, J = 3.0 Hz, 1H), 8.26 (d, J = 5.2 Hz, 1H), 7.95 (dd, J =8.9, 2.6 Hz,1H), 7.64 (d, J = 1.8 Hz, 1H), 6.98 – 6.94 (m, 2H), 6.41 (d, J =8.7 Hz, 1H), 4.71 (s, 4H), 4.03 (s, 4H), 3.73 (s, 3H), 3.06 (s, 6H). 13 C NMR(101 MHz, DMSO-D6) δ 162.96, 161.15, 160.82, 158.30, 156.89, 139.79, 130.45,129.29, 127.47, 127.36, 121.33, 111.13, 106.88, 106.32, 80.55, 60.68, 46.06,38.89, 36.27. LC-MS: m / z: calculated for C 22 H 25 N7O2([M+H) + ):420.2070, find:420.2484.

[0061] (20) Preparation of 9-(5-((4-(5-(dimethylcarbamoyl)-1-methyl-1H-pyrrolo-3-yl)pyrimidin-2-yl)amino)pyridin-2-yl)-3,9-diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester (10t): Using 4-(2-chloropyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrolo-2-carboxamide (9) and 9-(5-aminopyridin-2-yl)-3,9-diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester (3t) as raw materials, the preparation method is the same as in 10a, and 0.22 g of yellow solid is obtained, with a yield of 50.69%. 1HNMR (400 MHz, DMSO-d6) δ 9.12 (s, 1H), 8.42 (d, J = 2.7 Hz, 1H), 8.26 (d, J =5.2 Hz, 1H), 7.94 (dd, J = 9.1, 2.7 Hz,1H), 7.64 (d, J = 1.8 Hz, 1H), 6.97 –6.94 (m, 2H), 6.81 (d, J = 9.1 Hz, 1H), 3.73 (s, 3H), 3.43 – 3.39 (m, 4H),3.31 (d, J = 5.7 Hz, 4H), 3.06 (s, 6H),1.49 (t, J = 5.8 Hz, 4H), 1.38 (s,13H). 13 C NMR (101 MHz, DMSO-D6) δ 162.86, 161.09, 160.75, 158.20, 155.40,154.43, 139.54, 130.39, 128.60, 127.34, 121.27, 111.07, 107.19, 106.75,78.87, 41.44, 36.28, 36.20, 35.32, 34.74, 30.17, 28.58. LC-MS: m / z:calculated for C 31 H 42 N8O3([M+H)) + ):575.3380, find:575.3926.

[0062] (21) Preparation of tert-butyl piperazine-1-carboxylate (10u): Using 4-(2-chloropyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrolo-2-carboxamide (9) and 4-(5-aminopyridin-2-yl)piperazine-1-carboxylate (3u) as raw materials, the preparation method is the same as in 10a, and 0.21 g of yellow solid is obtained, with a yield of 54.83%. 1H NMR (400 MHz, DMSO-d6) δ 9.17 (s, 1H), 8.45 (d, J = 2.8 Hz, 1H), 8.24 (d, J = 5.2 Hz, 1H), 7.98 (dd, J = 9.1, 2.7 Hz,1H), 7.61 (d, J = 1.8 Hz, 1H), 6.99 – 6.90 (m, 2H), 6.81 (d, J = 9.1 Hz, 1H), 3.70 (s, 3H), 3.42 – 3.32 (m, 8H), 3.03 (s, 6H), 1.38 (s, 9H). 13 C NMR (101 MHz, DMSO-D6) δ 162.95, 161.18, 160.76, 158.29, 155.02, 154.49, 139.38, 130.29,129.65, 127.48,127.38, 121.33, 111.13, 107.73, 106.97, 79.48, 45.87, 43.14,36.29, 33.81, 28.59. LC-MS: m / z: calculated for C 26 H 34 N8O3([M+H)) + ):507.2754,find:507.2872.

[0063] (22) Preparation of 4-(5-((4-(5-dimethylcarbamoyl)-1-methyl-1H-pyrrolo-3-yl)pyrimidin-2-yl)amino)pyridin-2-yl)-1,4-diaza-1-carboxylic acid tert-butyl ester (10v): Using 4-(2-chloropyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrolo-2-carboxamide (9) and 4-(5-aminopyridin-2-yl)-1,4-diaza-1-carboxylic acid tert-butyl ester (3v) as raw materials, the preparation method is the same as in 10a, and 0.20 g of brown solid is obtained, with a yield of 50.89%. 1H NMR (400 MHz, DMSO-d6) δ 9.03(s, 1H), 8.35 (d, J = 9.8 Hz, 1H), 8.24 (d, J = 5.1 Hz, 1H), 7.90 (d, J = 9.4Hz, 1H), 7.63 (s, 1H), 6.94 (dd, J = 3.5, 1.7 Hz, 2H), 6.65 (d, J = 7.9 Hz, 1H), 3.72 (s, 3H), 3.70 – 3.64 (m, 2H), 3.57 (d, J = 6.3 Hz, 2H), 3.51 (d, J =5.6 Hz, 1H), 3.46 (d, J = 5.4 Hz, 1H), 3.23 (t, J = 5.8 Hz, 1H), 3.18 – 3.15 (m, 1H), 3.06 (s, 6H), 1.80 (dt, J = 29.8, 6.0 Hz, 2H), 1.29 (d, J = 33.0 Hz, 9H). 13 C NMR (101 MHz, DMSO-D6) δ 162.96, 161.12, 160.92, 158.25, 154.97,154.75, 153.19, 140.22, 131.17, 127.59, 127.40, 121.37,111.15, 106.67,105.54, 78.88, 48.49, 48.13, 47.30, 46.93, 46.66, 46.32, 46.15, 45.67, 36.29,28.55, 28.41. LC-MS: m / z: calculated for C 27 H 36 N8O3([M+H)) + ):521.2910, find:521.3495.

[0064] (23) Preparation of N,N,1-trimethyl-4-(2-((6-(4-methyl-1,4-diazacycloheptane-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carboxamide (10w): Using 4-(2-chloropyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrole-2-carboxamide (9) and 6-(4-methyl-1,4-diazacycloheptane-1-yl)pyridin-3-amine (3w) as raw materials, the preparation method is the same as in 10a, and 0.12 g of yellow solid is obtained, with a yield of 36.58%. 1H NMR (400 MHz, DMSO-d6) δ 9.01 (s,1H), 8.32 (d, J = 2.7 Hz, 1H), 8.23 ​​(d, J = 5.2 Hz, 1H), 7.87 (dd, J = 9.1,2.7 Hz, 1H), 7.63 (d, J = 1.8 Hz, 1H), 6.95 – 6.92 (m, 2H), 6.58 (d, J = 9.1Hz, 1H), 3.72 (s, 3H), 3.71 – 3.68 (m, 2H), 3.54 (t, J = 6.2 Hz, 2H), 3.06 (s,6H), 2.59 – 2.56 (m, 2H),2.46 – 2.42 (m, 2H), 2.24 (s, 3H), 1.89 – 1.85 (m, 2H). 13 C NMR (101 MHz, DMSO-D6) δ 162.96, 161.13, 161.02, 158.25, 154.29,140.21, 131.28, 127.39, 127.34, 127.13, 121.39, 111.16, 106.63, 105.10,58.18, 57.27, 46.85, 46.63, 46.35, 36.28, 27.57. LC-MS: m / z: calculated forC 23 H 30 N8O ([M+H)) + ):435.2543, find:435.2597.

[0065] (24) Preparation of 4-(2-((6-(3,9-diazaspiro[5.5]undecane-3-yl)pyridin-3-yl)amino)pyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrole-2-carboxamide (11t): 9-(5-((4-(5-(dimethylcarbamoyl)-1-methyl-1H-pyrrole-3-yl)pyrimidin-2-yl)amino)pyridin-2-yl)-3,9-diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester (10t) (0.2g) was added to a round-bottom flask, and 20ml of dichloromethane:trifluoroacetic acid (TFA) = 3:1 was added. The mixture was stirred at room temperature for 2h. After the reaction was completed, saturated sodium bicarbonate solution was added for neutralization, followed by extraction with dichloromethane, drying with anhydrous sodium sulfate, and concentration under reduced pressure to obtain 0.10g of yellow solid, with a yield of 60.61%. 1H NMR (400 MHz, DMSO-d6) δ 9.12 (s, 1H), 8.42 (d, J= 2.7 Hz, 1H), 8.25 (d, J = 5.2 Hz, 1H), 7.94 (dd, J = 9.0, 2.7 Hz,1H), 7.63(d, J = 1.8 Hz, 1H), 6.97 – 6.94 (m, 2H), 6.79 (d, J = 9.1 Hz, 1H), 3.73 (s,3H), 3.42 – 3.37 (m, 4H), 3.06 (s, 6H), 2.70 (s, 4H), 1.50 – 1.44 (m, 4H),1.39 (t, J = 5.7 Hz, 4H). 13 C NMR (101 MHz, DMSO-D6) δ 162.96, 161.16, 160.85,158.27, 155.52, 139.64, 130.48, 128.60, 127.44, 127.36,121.36, 111.14,107.21, 106.81, 41.43, 41.14, 36.28, 35.85, 35.48, 30.20. LC-MS: m / z:calculated for C 26 H 34 N8O ([M+H)) + ):475.2856, find:475.3326.

[0066] (25) Preparation of N,N,1-trimethyl-4-(2-((6-(piperazin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carboxamide (11u): Using 4-(5-((4-(5-dimethylcarbamoyl)-1-methyl-1H-pyrrole-3-yl)pyrimidin-2-yl)amino)pyridin-2-yl)piperazin-1-carboxylic acid tert-butyl ester (10u) (0.2g) as raw material, the preparation method is the same as 11t, and 0.06g of yellow solid is obtained, with a yield of 37.50%. 1H NMR (400 MHz, DMSO-d6) δ 9.27 (s, 1H), 9.10 (s,1H), 8.52 (d, J = 2.7 Hz, 1H), 8.28 (d, J = 5.3 Hz, 1H), 8.06 (dd, J =9.1,2.7 Hz, 1H), 7.65 (d, J = 1.8 Hz, 1H), 6.99 (d, J = 5.2 Hz, 1H), 6.95 – 6.92(m, 2H), 3.72 (s, 3H), 3.64 – 3.60 (m, 4H), 3.19 (t, J = 5.3 Hz, 4H), 3.11 –2.98 (m, 6H). 13 C NMR (101 MHz, DMSO-D6) δ 162.95, 161.24, 160.62, 158.25,154.07,139.09, 130.38, 130.31, 127.53, 127.44, 121.27, 111.78, 108.20,107.12, 43.19, 42.93, 36.28. LC-MS: m / z: calculated for C 21 H 26 N8O ([M+H)) + ):407.2230, find:407.2378.

[0067] (26) Preparation of 4-(2-((6-(1,4-diaza-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrole-2-carboxamide (11v): 0.2 g of 4-(5-((4-(5-dimethylcarbamoyl)-1-methyl-1H-pyrrole-3-yl)pyrimidin-2-yl)amino)pyridin-2-yl)-1,4-diaza-1-carboxylic acid tert-butyl ester (10v) was used as the starting material. The preparation method was the same as in 11t, yielding 0.09 g of a yellowish-brown solid, with a yield of 56.25%. 1H NMR (400 MHz, DMSO-d6) δ 9.00 (s,1H), 8.32 (d, J = 2.7 Hz, 1H), 8.24 (d, J = 5.2 Hz, 1H), 7.87 (dd, J = 9.1,2.7 Hz, 1H), 7.63 (d, J = 1.8 Hz, 1H), 6.95 – 6.93 (m, 2H), 6.61 (d, J = 9.1Hz, 1H), 3.73 (s, 3H),3.66 – 3.61 (m, 4H), 3.06 (s, 6H), 2.89 – 2.85 (m, 2H),2.71 – 2.67 (m, 2H), 1.78 (dd, J = 11.5, 5.7 Hz, 2H), 1.27 – 0.78(m, 1H). 13 CNMR (101 MHz, DMSO-D6) δ 162.96, 161.14, 161.02, 158.26, 154.07, 140.36,131.32, 127.40, 127.34, 127.13, 121.38, 111.16, 106.63, 105.25, 49.98, 48.78,47.84,46.38, 36.29, 29.33. LC-MS: m / z: calculated for C 22 H 28 N8O ([M+H] + ):421.2386, find:421.2727。

[0068] (27) Preparation of N,N-diethyl-1-methyl-4-(2-(((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carboxamide (17a): 1-methyl-4-(2-(((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (16) (0.15 g, 394.31 μmol) was placed in a round-bottom flask with O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethylurea hexafluorophosphate (HATU) (0.16 g, 433.74 μmol) and triethylamine (0.12 g, 1.18 mmol). Acetonitrile was used as solvent and the reaction was activated at 0 °C for 1 h. After activation, diethylamine (0.03 g, 433.74 μmol) was added and the reaction was carried out at room temperature for 16 h. After the reaction was complete, the solvent was removed under reduced pressure, the mixture was dried, and purified by acidic silica gel column chromatography. The mobile phase was dichloromethane (DCM):methanol (MeOH) = 50:1, yielding 0.08 g of red solid, with a yield of 47.06%. 1 H NMR (400 MHz, DMSO-d6) δ9.20 (s, 1H), 8.52 (d, J = 2.7 Hz, 1H), 8.27 (d, J = 5.2 Hz, 1H), 7.99 (dd, J= 9.1, 2.7 Hz, 1H), 7.65 (d, J = 1.7 Hz, 1H), 6.98 (d, J =5.2 Hz, 1H), 6.87 –6.81 (m, 2H), 3.69 (d, J = 5.9 Hz, 7H), 3.44 (d, J = 7.1 Hz, 4H), 3.34 (d, J= 4.9 Hz, 4H),1.15 (d, J = 6.7 Hz, 6H). 13 C NMR (101 MHz, DMSO-D6) δ 162.70,161.13, 160.68, 158.44, 155.17, 139.15, 129.69, 128.23, 127.17, 127.01,121.34, 109.01, 107.48, 106.85, 66.50, 46.44, 41.91,36.02, 11.57. LC-MS: m / z:calculated for C 23 H 29 N7O2([M+H) + ):436.2383, find:436.2444.

[0069] (28) Preparation of (1-methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrolo-2-yl)(pyrrolidine-1-yl) methyl ketone (17b): Using 1-methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrolo-2-carboxylic acid (16) (0.15 g, 394.31 μmol) and pyrrolidine (0.03 g, 433.74 μmol) as raw materials, the preparation method was the same as in 17a, and 0.09 g of yellow solid was obtained, with a yield of 52.94%. 1 H NMR (400 MHz, DMSO-d6) δ 9.18 (s, 1H), 8.48 (d, J = 2.7 Hz, 1H), 8.28 (d, J = 5.2 Hz, 1H), 8.00 (dd, J = 9.1, 2.8Hz,1H), 7.65 (d, J = 1.7 Hz, 1H), 7.11 (d, J = 1.8 Hz, 1H), 7.00 (d, J = 5.2Hz, 1H), 6.83 (d, J = 9.1 Hz, 1H), 3.80 (s, 3H), 3.71 – 3.68 (m, 4H), 3.46(s, 4H), 3.34 (d, J = 4.9 Hz, 4H),1.88 – 1.83 (m, 4H). 13 C NMR (101 MHz, DMSO-D6) δ 161.13, 161.00, 160.75, 158.47, 158.17, 155.40, 139.62, 139.34, 130.35,129.70, 128.14, 121.27,111.81, 107.11, 66.53, 49.45, 46.46, 36.26, 26.65. LC-MS: m / z: calculated for C 23 H 27 N7O2([M+H) + ):434.2666, find:434.3347.

[0070] (29) Preparation of N-(2-(dimethylamino)ethyl)-N,1-dimethyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carboxamide (17c): Using 1-methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (16) (0.15 g, 394.31 μmol) and N,N,N-trimethylethylenediamine (0.04 g, 433.74 μmol) as raw materials, the preparation method is the same as in 17a, and 0.09 g of pale yellow solid (50.00%) is obtained. 1 H NMR (400 MHz, DMSO-d6) δ 9.18 (s, 1H), 8.50 (d, J = 2.7 Hz, 1H), 8.27 (d, J = 5.2 Hz, 1H), 8.00 (dd, J = 9.1, 2.8 Hz, 1H), 7.64 (d, J = 1.8 Hz, 1H), 6.97 (d, J =5.2 Hz,1H), 6.90 (s, 1H), 6.83 (d, J = 9.1 Hz, 1H), 3.72 – 3.69 (m, 7H), 3.58 (t, J= 6.4 Hz, 2H), 3.35 (s, 2H), 3.04 (s, 3H), 2.44 (s, 2H), 2.09 (s, 6H), 1.22 (s, 2H). 13 C NMR (101 MHz, DMSO-D6) δ 163.37, 161.15, 160.76, 158.49, 158.20,155.40, 139.55, 139.28, 130.29, 129.71, 127.50, 121.32,107.45, 107.33,107.06, 66.53, 46.96, 46.47, 44.73, 44.42, 36.27, 36.22. LC-MS: m / z:calculated for C 24 H 32 N8O2([M+H)) + ):465.2648, find:465.2540.

[0071] (30) Preparation of (1-methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrolo-2-yl)(4-methylpiperazin-1-yl) methyl ketone (17d): Using 1-methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrolo-2-carboxylic acid (16) (0.15 g, 394.31 μmol) and 1-methylpiperazine (0.04 g, 433.74 μmol) as raw materials, the preparation method was the same as in 17a, and 0.06 g of yellow solid was obtained, with a yield of 33.33%. 1 H NMR (400 MHz, DMSO-d6) δ 9.20(s, 1H), 8.50 (d, J = 2.7 Hz, 1H), 8.28 (d, J = 5.2 Hz, 1H), 8.00 (dd, J =9.1, 2.7 Hz,1H), 7.68 (d, J = 1.8 Hz, 1H), 6.99 (d, J = 5.2 Hz, 1H), 6.89 (d,J = 1.8 Hz, 1H), 6.83 (d, J = 9.1 Hz, 1H), 3.73 (s, 3H), 3.70 (t, J = 4.8 Hz,4H), 3.35 (d,J = 4.9 Hz, 4H), 2.87 (d, J = 13.9 Hz, 4H), 2.45 (s, 4H), 2.28 (s, 3H). 13 C NMR (101 MHz, DMSO-D6) δ 161.91, 161.00, 160.74, 158.20, 155.40,139.24, 130.36, 129.71, 127.88, 126.77,121.52, 110.95, 107.44, 107.28, 66.52,54.36, 51.73, 46.46, 43.42, 36.32. LC-MS: m / z: calculated for C 24 H 30 N8O2([M+H)) + ):463.2492, find:463.7493.

[0072] (31) Preparation of (1-methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrolo-2-yl)(4-methylpiperidin-1-yl)methyl ketone (17e): Using 1-methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrolo-2-carboxylic acid (16) (0.15 g, 394.31 μmol) and 4-methylpiperidine (0.04 g, 433.74 μmol) as raw materials, the preparation method is the same as in 17a, and 0.08 g of yellow solid is obtained, with a yield of 44.44%. 1 H NMR (400 MHz, DMSO-d6) δ 9.20(s, 1H), 8.50 (d, J = 2.7 Hz, 1H), 8.27 (d, J = 5.2 Hz, 1H), 8.00 (dd, J =9.1, 2.7 Hz,1H), 7.66 (d, J = 1.8 Hz, 1H), 6.98 (d, J = 5.2 Hz, 1H), 6.85 –6.81 (m, 2H), 3.69 (d, J = 6.6 Hz, 7H), 3.35 (s, 4H), 1.68 (d, J = 12.2 Hz,4H), 1.25 – 1.04(m, 5H), 0.94 (d, J = 6.0 Hz, 3H). 13 C NMR (101 MHz, DMSO-D6) δ161.69, 161.06, 160.73, 158.33, 155.37,139.38, 130.24, 129.74, 127.65,127.32, 121.40, 110.05, 107.33, 106.93, 66.52, 46.47, 36.07, 34.54, 31.15,22.16. LC-MS: m / z: calculated for C 25 H 31 N7O2([M+H) + ):462.2539, find:462.3140.

[0073] (32) Preparation of (4-(dimethylamino)piperidin-1-yl)(1-methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-yl)methyl ketone (17f): Using 1-methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (16) (0.15 g, 394.31 μmol) and 4-dimethylaminopiperidine (0.06 g, 433.74 μmol) as raw materials, the preparation method was the same as in 17a, and 0.07 g of red solid was obtained, with a yield of 31.58%. 1 H NMR (400 MHz, DMSO-d6) δ 9.21 (s, 1H), 8.49 (d, J = 2.7 Hz, 1H), 8.29 (d, J = 5.2 Hz, 1H), 8.03 (dd, J = 9.1, 2.7 Hz,1H), 7.68 (d, J = 1.8 Hz, 1H), 7.00 (d, J = 5.2 Hz, 1H), 6.90 (d, J = 1.8 Hz, 1H), 6.84 (d, J = 9.1 Hz, 1H), 3.73 – 3.69(m, 7H), 3.36 (s, 4H), 2.95 (s, 2H), 2.91 – 2.84 (m, 1H), 2.43 (s, 6H), 1.99 – 1.93 (m, 2H), 1.56 – 1.46 (m, 2H), 1.23 (s, 2H). 13 C NMR (101 MHz, DMSO-D6) δ 161.80,161.07, 160.74, 158.34, 155.39, 139.34, 130.21, 129.74, 127.55, 127.27,121.43, 110.38, 107.38, 106.99, 66.53, 62.16, 46.48, 36.13, 29.57, 27.78. LC-MS: m / z: calculated for C 26 H 34 N8O2([M+H)) + ):491.2805, find:491.3436.

[0074] (33) Preparation of (4-methoxypiperidin-1-yl)(1-methyl-4-(2-((6-morpholinylpyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-yl)methyl ketone (17 g): Using 1-methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (16) (0.15 g, 394.31 μmol) and 4-methoxypiperidine (0.05 g, 433.74 μmol) as raw materials, the preparation method is the same as in 17a, and 0.08 g of yellow solid is obtained, with a yield of 42.55%. 1 H NMR (400 MHz, DMSO-d6) δ9.20 (s, 1H), 8.50 (d, J = 2.7 Hz, 1H), 8.27 (d, J = 5.2 Hz, 1H), 8.00 (dd, J= 9.1, 2.7 Hz, 1H), 7.67 (d, J = 1.7 Hz, 1H), 6.98 (d, J =5.2 Hz, 1H), 6.88(d, J = 1.8 Hz, 1H), 6.82 (d, J = 9.1 Hz, 1H), 3.93 – 3.88 (m, 2H), 3.70 (d,J = 3.2 Hz, 9H), 3.45 (dt, J = 8.1, 4.3 Hz, 1H), 3.34 (d, J = 5.0 Hz, 4H), 3.27 (s, 3H), 1.89 (d, J = 14.8 Hz, 2H), 1.50 – 1.43 (m, 2H). 13 C NMR (101 MHz, DMSO-D6) δ 161.81, 161.03, 160.73, 158.36, 155.39, 139.44, 130.30, 129.71,127.43, 127.39, 121.43, 110.31,107.32, 106.94, 75.72, 66.53, 55.63, 46.46,36.08, 31.28. LC-MS: m / z: calculated for C 25 H 31 N7O3([M+H)) + ):478.2488, find:478.3109.

[0075] (34) Preparation of (1-methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-yl)(4-(methanesulfonyl)piperazin-1-yl)methyl ketone (17h): Using 1-methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (16) (0.15 g, 394.31 μmol) and 1-(methanesulfonyl)piperazine (0.07 g, 433.74 μmol) as raw materials, the preparation method is the same as in 17a, and 0.10 g of grayish-white solid is obtained, with a yield of 48.31%. 1 H NMR (400MHz, DMSO-d6) δ 9.22 (s, 1H), 8.49 (d, J = 2.7 Hz, 1H), 8.29 (d, J = 5.2 Hz,1H), 8.03 (dd, J = 9.1, 2.7 Hz,1H), 7.70 (d, J = 1.8 Hz, 1H), 6.99 (d, J =5.2 Hz, 1H), 6.94 (d, J = 1.8 Hz, 1H), 6.84 (d, J = 9.1 Hz, 1H), 3.75 (s,7H), 3.70 (d, J = 5.1 Hz, 4H), 3.35 (d,J = 2.8 Hz, 4H), 3.21 (t, J = 5.0 Hz, 4H), 2.92 (s, 3H). 13 C NMR (101 MHz, DMSO-D6) δ 162.03, 160.99, 160.75, 158.41,155.43, 139.36, 130.28, 129.72, 127.92, 126.70, 121.55, 111.26,107.38,107.00, 66.53, 46.47, 46.01, 36.22, 34.68. LC-MS: m / z: calculated forC 24 H 30 N8O4S ([M+H) + ):527.2111, find:527.2784.

[0076] (35) Preparation of (1-methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-yl)(4-(trifluoromethyl)piperidin-1-yl)methyl ketone (17i): Using 1-methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (16) (0.15 g, 394.31 μmol) and 4-(trifluoromethyl)piperidine (0.06 g, 433.74 μmol) as raw materials, the preparation method is the same as in 17a, and 0.11 g of yellow solid is obtained, with a yield of 54.19%. 1 H NMR (400 MHz, DMSO-d6) δ 7.86 (s, 1H), 7.30 (d, J = 2.1 Hz, 1H), 7.12 (d, J = 4.2 Hz, 1H), 6.91 (dd, J = 7.3, 2.2 Hz, 1H), 6.64 (d, J = 1.4 Hz, 1H), 6.10 (d, J = 4.2 Hz, 1H), 6.02 (d, J = 1.4 Hz, 1H), 5.95 (d, J = 7.3 Hz, 1H), 3.48 (s, 3H), 3.47 –3.44(m, 4H), 3.17 (d, J = 4.1 Hz, 4H), 2.88 (s, 1H), 2.87 – 2.74 (m, 4H), 2.02 (d, J = 9.2 Hz, 2H), 1.71 – 1.64 (m, 2H). 13 C NMR (101 MHz, DMSO-D6) δ161.98, 161.04, 160.73, 158.46, 155.38,139.48, 130.22, 129.75, 127.68,127.12, 121.47, 110.62, 107.31, 107.08, 66.53, 47.09, 46.45, 46.43, 36.18,36.13, 24.97. LC-MS: m / z: calculated for C 25 H 28 F3N7O2([M+H) + ):516.2257, find:516.2356.

[0077] (36) Preparation of (4,4-difluoropiperidin-1-yl)(1-methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-yl) methyl ketone (17j): Using 1-methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (16) (0.15 g, 394.31 μmol) and 4,4-difluoropiperidin (0.05 g, 433.74 μmol) as raw materials, the preparation method was the same as in 17a, and 0.09 g of yellow solid was obtained, with a yield of 47.12%. 1 H NMR (400 MHz, DMSO-d6) δ9.20 (s, 1H), 8.51 (d, J = 2.7 Hz, 1H), 8.28 (d, J = 5.2 Hz, 1H), 7.99 (dd, J= 9.1, 2.7 Hz,1H), 7.69 (d, J = 1.8 Hz, 1H), 7.01 – 6.97 (m, 2H), 6.83 (d, J= 8.8 Hz, 1H), 3.74 (s, 7H), 3.71 – 3.68 (m, 4H), 3.34 (d, J = 4.8 Hz, 4H), 2.06 (d, J =14.6 Hz, 4H). 13 C NMR (101 MHz, DMSO-D6) δ 162.11, 160.96, 160.74,158.54, 155.40, 139.60, 139.35, 130.37, 129.68, 127.82, 126.72, 121.50,111.16, 107.37, 66.52, 46.45, 38.76,36.21, 34.10. LC-MS: m / z: calculated forC 24 H 27 F2N7O2([M+H) + ):484.2194, find:484.1311.

[0078] (37) Preparation of (1-methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-yl)(4-(oxecyclobutane-3-yl)piperazin-1-yl) methyl ketone (17k): Using 1-methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (16) (0.15 g, 394.31 μmol) and 1-(oxecyclobutane-3-yl)piperazine (0.06 g, 433.74 μmol) as raw materials, the preparation method is the same as in 17a, and 0.08 g of yellow solid is obtained, with a yield of 40.41%. 1 H NMR(400 MHz, DMSO-d6) δ 9.20 (s, 1H), 8.49 (d, J = 2.6 Hz, 1H), 8.28 (d, J = 5.2Hz, 1H), 8.01 (dd, J = 9.1, 2.7 Hz, 1H), 7.68 (d, J = 1.8 Hz, 1H), 6.99 (d, J=5.2 Hz, 1H), 6.89 – 6.82 (m, 2H), 4.55 (t, J = 6.5 Hz, 2H), 4.46 (t, J = 6.0Hz, 2H), 3.72 (d, J = 4.9 Hz, 7H), 3.65 (d, J = 5.7 Hz, 4H), 3.44 (q, J = 6.3Hz, 1H), 3.35 (d, J = 4.9 Hz, 4H), 2.32 (t, J = 4.9 Hz, 4H). 13 C NMR (101 MHz, DMSO-D6) δ 162.31, 161.87, 161.04, 160.73, 158.35, 155.40, 139.35, 130.29,129.72, 127.61, 127.11, 121.47, 110.77, 107.40, 106.98, 74.78, 66.53,58.79,58.59, 49.65, 48.70, 48.05, 46.47, 36.12. LC-MS: m / z: calculated for C 26 H 32 N8O3([M+H)) + ):505.2597, find:505.3590.

[0079] (38) Preparation of (1-methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-yl)(4-morpholinopiperidin-1-yl) methyl ketone (17l): Using 1-methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (16) (0.15 g, 394.31 μmol) and 4-(4-piperidinyl)morpholine (0.07 g, 433.74 μmol) as raw materials, the preparation method is the same as in 17a, and 0.12 g of yellow solid is obtained, with a yield of 57.14%. 1 H NMR (400 MHz, Chloroform-d) δ 8.36 (s, 1H), 8.24 (d, J = 5.3 Hz, 1H), 7.90 (dd, J = 9.0,2.8 Hz, 1H), 7.37 (s, 1H), 7.16 (s, 1H), 6.80 – 6.73 (m, 2H), 6.67 (d, J =9.0 Hz, 1H), 3.83 (t, J = 4.9Hz, 4H), 3.79 (s, 3H), 3.72 (t, J = 4.6 Hz, 4H), 3.44 (t, J = 4.8 Hz, 4H), 2.57 (d, J = 4.6 Hz, 4H), 2.51 – 2.41 (m, 1H), 1.94 (d, J = 11.7 Hz, 2H), 1.51 (t, J = 12.0 Hz, 2H), 1.24 (s, 4H). 13 C NMR (101MHz, CHLOROFORM-D) δ 162.20, 161.37,160.61, 157.80, 156.23, 140.39, 131.14,128.27, 126.97, 126.86, 121.52, 110.68, 107.12, 107.07, 67.24, 66.88, 62.06,49.93, 46.47, 36.26, 29.78, 28.81, 1.09.LC-MS: m / z: calculated for C 28 H 36 N8O3([M+H)) + ):533.2910, find:533.3961.

[0080] (39) Preparation of (4-methyl-1,4-diazacycloheptane-1-yl)(1-methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-yl) methyl ketone (17m): Using 1-methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (16) (0.15 g, 394.31 μmol) and N-methylperiprazine (0.05 g, 433.74 μmol) as raw materials, the preparation method was the same as in 17a, and 0.11 g of yellow solid was obtained, with a yield of 58.51%. 1 H NMR (400MHz, DMSO-d6) δ 9.19 (s, 1H), 8.51 (d, J = 2.7 Hz, 1H), 8.27 (d, J = 5.2 Hz, 1H), 7.99 (dd, J = 9.1, 2.6 Hz, 1H), 7.66 (d, J = 1.7 Hz, 1H), 6.97 (d, J =5.2 Hz, 1H), 6.89 (s, 1H), 6.82 (d, J = 9.1 Hz, 1H), 3.74 – 3.68 (m, 9H), 3.61 (s, 2H), 3.34 (d, J = 4.9 Hz, 4H), 2.69 – 2.63 (m, 2H), 2.59 – 2.53 (m,2H), 2.30 (s, 3H), 1.87 (s, 2H). 13 C NMR (101 MHz, DMSO-D6) δ 163.05, 161.09,160.74, 158.34, 155.37, 139.40, 130.26, 129.73, 127.88, 127.34,121.36,110.36, 107.34, 106.94, 66.53, 46.47, 46.28, 36.27. LC-MS: m / z: calculatedfor C 25 H 32 N8O2([M+H)) + ):477.2648, find:477.3736.

[0081] (40) Preparation of (1-methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-yl)(2-oxa-6-azaspiro[3.3]heptane-6-yl) methyl ketone (17n): Using 1-methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (16) (0.15 g, 394.31 μmol) and 2-oxa-6-azaspiro[3.3]heptane (0.04 g, 433.74 μmol) as raw materials, the preparation method is the same as in 17a, and 0.10 g of yellow solid (54.95%) is obtained. 1 H NMR(400 MHz, DMSO-d6) δ 9.22 (s, 1H), 8.52 (d, J = 2.7 Hz, 1H), 8.30 (d, J = 5.2Hz, 1H), 7.99 (dd, J = 9.1, 2.8 Hz,1H), 7.70 (d, J = 1.8 Hz, 1H), 7.08 (d, J= 1.8 Hz, 1H), 7.02 (d, J = 5.2 Hz, 1H), 6.86 (d, J = 9.1 Hz, 1H), 4.70 (s,4H), 3.86 (s, 3H), 3.71 (t, J = 4.8 Hz,4H), 3.36 (d, J = 4.8 Hz, 4H), 1.22 (s, 4H). 13 C NMR (101 MHz, DMSO-D6) δ 162.34, 160.82, 160.73, 158.51, 155.43,139.54, 130.43, 129.67, 128.92, 125.12, 121.70, 112.65,107.36, 106.96, 80.25,66.52, 46.45,38.41,38.28, 37.36. LC-MS: m / z: calculated for C 24 H 27 N7O3([M+H)) + ):462.2175, find:462.3056.

[0082] (41) Preparation of tert-butyl 4-(1-methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carbonyl)piperazine-1-carboxylate (17o): Using 1-methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (16) (0.15 g, 394.31 μmol) and 1-(tert-butyloxycarbonyl)piperazine (0.09 g, 433.74 μmol) as raw materials, the preparation method is the same as in 17a, and 0.15 g of gray solid is obtained, with a yield of 69.44%. 1 H NMR (400 MHz, Chloroform-d) δ 8.38 (d, J = 2.6 Hz, 1H), 8.25 (d, J = 5.2 Hz, 1H), 7.91 (dd,J = 9.0, 2.7 Hz, 1H), 7.39 (d, J = 1.8 Hz, 1H), 7.06 (s, 1H), 6.81 (d, J =1.8Hz, 1H), 6.76 (d, J = 5.3 Hz, 1H), 6.68 (d, J = 9.0 Hz, 1H), 3.86 – 3.82 (m,7H), 3.74 (t, J = 5.2 Hz, 4H), 3.52 – 3.48 (m, 4H), 3.47 – 3.43 (m, 4H), 1.48 (s, 9H). 13 C NMR (101 MHz, CHLOROFORM-D) δ 162.54, 161.14, 160.63, 157.93,156.27, 154.68, 140.45, 131.17, 128.20, 127.21, 126.37, 121.68, 111.36,107.08, 80.51, 66.89, 46.45,36.39, 29.78, 28.47, 1.10. LC-MS: m / z: calculated for C 28 H 36 N8O4([M+H)) + ):549.2860, find:549.3227.

[0083] (42) Preparation of tert-butyl 4-(1-methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carbonyl)-1,4-diaza-1-carboxylic acid (17p): Using 1-methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (16) (0.15 g, 394.31 μmol) and tert-butyl 1,4-diazacycloheptane-1-carboxylic acid (0.09 g, 433.74 μmol) as raw materials, the preparation method was the same as in 17a, and 0.15 g of yellow solid was obtained, with a yield of 67.57%. 1 H NMR(400 MHz, DMSO-d6) δ 9.19 (s, 1H), 8.49 (d, J = 11.0 Hz, 1H), 8.27 (d, J =2.9 Hz, 1H), 7.99 (d, J = 9.6 Hz, 1H), 7.66 (d, J = 9.8 Hz, 1H), 6.99 – 6.89(m, 2H), 6.81 (d, J = 9.1 Hz, 1H), 3.70 (d, J = 4.5 Hz, 4H), 3.67 (s, 3H), 3.60 (s, 2H), 3.48 (d, J = 6.5 Hz, 2H), 3.38 (s, 2H), 3.33 (s, 4H), 2.86 (s,2H), 1.74 (s, 2H), 1.38 (d, J = 10.2 Hz, 9H). 13 C NMR (101 MHz, DMSO-D6) δ163.75, 163.11, 161.05, 160.74, 158.40,155.38, 154.88, 139.38, 130.24,129.73, 127.55, 127.45, 121.39, 107.36, 106.91, 79.57, 79.26, 66.53, 46.46,36.10, 28.56, 28.39. LC-MS: m / z: calculated for C 29 H 38 N8O4([M+H)) + ):563.3016,find:563.5487.

[0084] (43) Preparation of tert-butyl 9-(1-methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carbonyl)-3,9-diazaspiro[5.5]undecane-3-carboxylic acid (17q): Using 1-methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carboxylic acid (16) (0.15 g, 394.31 μmol) and tert-butyl 3,9-diazaspiro[5.5]undecane-3-carboxylic acid (0.11 g, 433.74 μmol) as raw materials, the preparation method was the same as in 17a, and 0.16 g of yellow solid was obtained, with a yield of 65.84%. 1 H NMR (400 MHz, DMSO-d6) δ 9.20 (s, 1H), 8.51 (d, J = 2.7Hz, 1H), 8.27 (d, J = 5.2 Hz, 1H), 8.01 (dd, J = 9.1, 2.7 Hz,1H), 7.67 (d, J= 1.8 Hz, 1H), 6.98 (d, J = 5.2 Hz, 1H), 6.87 (d, J = 1.8 Hz, 1H), 6.82 (d, J= 9.1 Hz, 1H), 3.72 – 3.69(m, 7H), 3.59 (d, J = 6.6 Hz, 4H), 3.34 (d, J = 5.2Hz, 4H), 3.31 (s, 4H), 1.50 (d, J = 5.5 Hz, 4H), 1.44 (d, J = 5.7 Hz, 4H), 1.38 (s, 9H). 13 C NMR (101 MHz, DMSO-D6) δ 161.67, 161.04, 160.71, 158.37,155.36, 154.48, 139.29, 130.25, 129.76, 127.48, 127.42, 121.39,110.20,107.37, 106.88, 79.01, 66.52, 46.49, 36.11, 35.52, 35.46, 35.41, 30.81,28.62. LC-MS: m / z: calculated for C 33 H 44 N8O4([M+H)) + ):617.3486, find:617.4830.

[0085] (44) Preparation of (1-methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-yl)piperazin-1-yl)methyl ketone (18o): 0.15 g of 4-(1-methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carbonyl)piperazin-1-carboxylic acid tert-butyl ester (17o) was added to a round-bottom flask, and 20 mL of dichloromethane:trifluoroacetic acid (TFA) = 3:1 was added. The mixture was stirred at room temperature for 2 h. After the reaction was completed, saturated sodium bicarbonate solution was added for neutralization, followed by extraction with dichloromethane, drying with anhydrous sodium sulfate, and concentration under reduced pressure to obtain 0.09 g of yellow solid, with a yield of 73.77%. 1 H NMR (400 MHz, DMSO-d6) δ 9.19 (s, 1H), 8.48 (dd, J = 5.7, 2.7 Hz, 1H), 8.27 (d, J = 5.2 Hz, 1H), 8.00 (t, J = 9.9 Hz,1H), 7.66 (s, 1H), 7.00 – 6.96 (m, 1H), 6.87 – 6.81 (m,2H), 3.72 – 3.68 (m, 7H), 3.56 – 3.47(m, 4H), 3.35 (s, 6H), 2.71 (t, J = 5.0Hz, 2H). 13 C NMR (101 MHz, DMSO-D6) δ 161.83, 161.47, 161.10, 160.74, 158.31,157.99, 155.40, 139.43, 130.28, 130.16, 129.71, 127.34,121.76, 110.40,107.34, 106.99, 66.54, 46.47, 36.57. LC-MS: m / z: calculated for C 23 H 28 N8O2([M+H)) + ):449.2335, find:449.2467.

[0086] (45) Preparation of (1,4-diaza-1-yl)(1-methyl-4-(2-((6-morpholinpyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-yl)methyl ketone (18p): Using 0.15 g of 4-(1-methyl-4-(2-((6-morpholinpyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrole-2-carbonyl)-1,4-diaza-1-carboxylic acid tert-butyl ester (17p) as the starting material, the preparation method was the same as that of 18o, and 0.08 g of yellow solid was obtained, with a yield of 65.04%. 1 H NMR (400 MHz, DMSO-d6) δ 9.19 (s, 1H), 8.51 – 8.46 (m, 1H), 8.27 – 8.24 (m, 1H), 7.99 (td, J = 8.8, 2.7Hz, 1H), 7.65 (s, 1H), 6.96 (d, J = 5.2 Hz, 1H), 6.92 – 6.79 (m, 2H), 3.69 (d, J = 3.0 Hz, 4H), 3.67 (d, J = 1.9 Hz, 3H), 3.65 – 3.52 (m, 4H), 3.45 (s, 2H), 3.34 (d, J=1.7 Hz, 6H), 1.75 – 1.65 (m, 2H), 1.21 (s, 1H). 13 C NMR (101 MHz, DMSO-D6) δ163.16, 161.12, 160.72, 158.33, 155.37, 154.82, 139.37, 138.81, 130.28,129.73, 127.11, 121.31, 107.36, 106.94, 66.53, 47.74, 47.07,36.14, 26.05,14.49. LC-MS: m / z: calculated for C 24 H 30 N8O2([M+H)) + ):463.2492, find:463.2596.

[0087] (46) Preparation of (1-methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrolo-2-yl)(3,9-diazaspiro[5.5]undecane-3-yl)methyl ketone (18q): Using 0.15 g of 9-(1-methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrolo-2-carbonyl)-3,9-diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester (17q) as raw material, the preparation method was the same as that in 18o, and 0.10 g of yellow solid was obtained, with a yield of 79.36%. 1 H NMR (400 MHz, DMSO-d6) δ 9.21 (s, 1H), 8.51 (d, J = 2.7 Hz, 1H), 8.27 (d, J = 5.2 Hz, 1H), 8.01 (dd, J = 9.0, 2.8 Hz, 1H), 7.67 (d, J = 1.8 Hz, 1H), 6.98 (d, J =5.2 Hz,1H), 6.87 – 6.81 (m, 2H), 3.70 (q, J = 5.6, 3.9 Hz, 7H), 3.62 – 3.57(m, 4H), 3.35 (s, 4H), 3.29 (s, 2H), 2.66 (d, J = 5.5 Hz, 2H), 1.47 (t, J = 5.8 Hz, 4H), 1.40 (t, J = 4.6 Hz, 4H), 1.22 (s, 1H). 13 C NMR (101 MHz, DMSO-D6) δ161.68, 161.06, 160.71, 158.33, 155.36, 139.35, 130.22, 129.76, 127.56,127.37, 121.38, 110.13,107.34, 106.93, 66.52, 46.48, 41.52, 36.09, 30.87. LC-MS: m / z: calculated for C 28 H 36 N8O2([M+H)) + ):517.2961, find:517.3099.

[0088] Example 14 Cytotoxicity evaluation of the target compound.

[0089] CCK8 assay for MDA-MB-231 cell viability: Remove T25 culture dishes from the incubator, wash 1-2 times with PBS, digest with 2 mL of trypsin for 2.5 min, and add 4 mL of complete culture medium to stop digestion; transfer the above liquid to 10 mL centrifuge tubes and seal with sealing film; centrifuge at 1000 rpm for 5 min and discard the supernatant. Add 1 mL of complete culture medium to the centrifuge tubes and mix well to form a cell suspension; count the cells and adjust the cell count to 1 × 10⁻⁶. 4 / well (96-well plate, 100µl cell suspension per well), incubate for 24 hours to allow cell adhesion; discard the culture medium, add drug (96-well plate, 100µl per well), incubate for 24 hours; discard the culture medium, add prepared CCK8 solution (CCK8: serum-free medium = 1:10), 100µl per well, incubate for 3 hours in the dark; use a microplate reader at 450nm wavelength, read the values; cell viability = (experimental group OD - blank group OD) / (control group OD - blank group OD) × 100%; calculate IC50 using Prism software. 50 The results are summarized in Table 1.

[0090] Table 1. Cytotoxicity results of the compounds Note: "--" indicates that no activity was detected.

[0091] MCF-10A cell CCK8 activity assay: Remove the T25 culture dish from the incubator, wash 1-2 times with PBS, digest with 2 mL of trypsin for 2.5 min, add 4 mL of complete culture medium to stop digestion, transfer the liquid to a 10 mL centrifuge tube, seal with sealing film, centrifuge at 1000 rpm for 5 min, and discard the supernatant. Add 1 mL of complete culture medium to the centrifuge tube and mix well to form a cell suspension. Count the cells and adjust the cell count to 1 × 10⁻⁶. 4 / well (96-well plate, 100 μL cell suspension per well), incubate for 24 h to allow cell adhesion, discard the suspension, add drug (96-well plate, 100 μL per well), incubate for 24 h, discard the suspension, add prepared CCK8 solution (CCK8: serum-free medium = 1:10), 100 μL per well, incubate for 3 h in the dark, use a microplate reader at 450 nm wavelength, read the cell viability = (experimental group OD - blank group OD) / (control group OD - blank group OD) × 100%, calculate IC50 using Prism software.

[0092] Calculation and determination of the selectivity index (SI): Judgment criteria: SI > 2 indicates that the compound has low toxicity to normal cells and good selectivity; SI < 2 indicates significant toxicity to normal cells and poor selectivity. The results are summarized in Table 2.

[0093] Table 2 Selectivity index of preferred compounds for MCF-10A cells Note: "SI≥2" indicates that the compound has low toxicity to normal cells and good selectivity.

Claims

1. A novel 4-(1 H (-pyrrole-3-yl)pyrimidine anti-breast cancer compounds, characterized in that... As shown in general formulas I and II: in: Each R1 is independently dimethylamino, diethylamino, pyrrolyl, N,N,N-trimethylethane-1,2-diamino, morpholino, thiomorpholino, N-methylpiperazinyl, 4-methylpiperidinyl, N,N,-dimethylpiperidin-4-amino, N-isopropylpiperazinyl, N-ethylpiperazinyl, 4-methoxypiperidinyl, N-methanesulfonylpiperazinyl, 4-trifluoromethylpiperidinyl, 4,4-difluoropiperidinyl, 4-cyclopropylpiperazinyl, N-( oxacyclobutane-3-yl)piperazinyl, 4-(4-piperidinyl)morpholinyl, 2-oxa-6-aza-spiro[3,3]heptyl, 3,9-diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester, 1-tert-butoxycarbonylpiperazinyl, 1-Boc-hexahydro-1,4-diazacycloheptyl, 4-methyl-1,4-diazacycloheptyl, 3,9-diazaspiro[5.5]undecane-3-yl, piperazinyl, high-piperazinyl; Each R2 is independently benzyloxy, hydroxy, diethylamino, N,N,N-trimethylethane-1,2-diamino, N-methylpiperazinyl, 4-methylpiperidinyl, N,N,-dimethylpiperidin-4-amino, 4-methoxypiperidinyl, N-methanesulfonylpiperazinyl, 4-trifluoromethylpiperidinyl, 4,4-difluoropiperidinyl, N-(oxetane-3-yl)piperazinyl, 4-(4- Piperidinyl)morpholinyl, 4-methyl-1,4-diazacycloheptyl, 2-oxa-6-aza-spiro[3,3]heptyl, 1-tert-butoxycarbonylpiperazinyl, 1-Boc-hexahydro-1,4-diazacycloheptyl, 3,9-diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester, piperazinyl, high-piperazinyl, 3,9-diazaspiro[5.5]undecane-3-yl.

2. The 4-(1) according to claim 1 H (-pyrrole-3-yl)pyrimidine anti-breast cancer compounds, characterized in that... The novel compounds represented by general formulas I and II include 4-(1 H 3-pyrrolo-3-yl)pyrimidine compounds and their derivatives, tautomers, and pharmaceutically acceptable salts, hydrates, or solvates.

3. The 4-(1) according to claim 2 H (-pyrrole-3-yl)pyrimidine anti-breast cancer compounds, characterized in that... The compound of general formula I or its pharmaceutically acceptable salt, hydrate or solvate is specifically: 4-(2-((6-(dimethylamino)pyridin-3-yl)amino)pyrimidin-4-yl)- N,N, 1-Trimethyl-1 H -Pyrrole-2-carboxamide; 4-(2-((6-(diethylamino)pyridin-3-yl)amino)pyrimidin-4-yl)- N,N, 1-Trimethyl-1 H -Pyrrole-2-carboxamide; N,N 1-Trimethyl-4-(2-((6-(pyrrolidin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)-1 H -Pyrrole-2-carboxamide; 4-(2-((6-((2-(dimethylamino)ethyl)(methyl)amino)pyridin-3-yl)amino)pyrimidin-4-yl)- N,N, 1-Trimethyl-1 H -Pyrrole-2-carboxamide; N,N 1-Trimethyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1 H -Pyrrole-2-carboxamide; N,N 1-Trimethyl-4-(2-((6-thiomorpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1 H -Pyrrole-2-carboxamide; N,N 1-Trimethyl-4-(2-((6-(4-methylpiperazin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)-1 H -Pyrrole-2-carboxamide; N,N 1-Trimethyl-4-(2-((6-(4-methylpiperidin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)-1 H -pyrrole-2-carboxamide 4-(2-((6-(4-(dimethylamino)piperidin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)- N,N, 1-Trimethyl-1 H -Pyrrole-2-carboxamide; 4-(2-((6-(4-isopropylpiperazin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)- N,N, 1-Trimethyl-1 H -Pyrrole-2-carboxamide; 4-(2-((6-(4-ethylpiperazin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)- N,N, 1-Trimethyl-1 H -Pyrrole-2-carboxamide; 4-(2-((6-(4-methoxypiperidin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)- N,N, 1-Trimethyl-1 H -Pyrrole-2-carboxamide; N,N 1-Trimethyl-4-(2-((6-(4-(methanesulfonyl)piperazin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)-1 H -Pyrrole-2-carboxamide; N,N 1-Trimethyl-4-(2-((6-(4-(trifluoromethyl)piperidin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)-1 H -Pyrrole-2-carboxamide; 4-(2-((6-(4,4-difluoropiperidin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)- N,N, 1-Trimethyl-1 H -Pyrrole-2-carboxamide; 4-(2-((6-(4-cyclopropylpiperazin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)- N,N, 1-Trimethyl-1 H -Pyrrole-2-carboxamide; N,N 1-Trimethyl-4-(2-((6-(4-(oxecyclobutane-3-yl)piperazin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)-1 H -Pyrrole-2-carboxamide; N,N 1-Trimethyl-4-(2-((6-(4-morpholinopiperidin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)-1 H -Pyrrole-2-carboxamide; 4-(2-((6-(2-oxa-6-azaspiro[3.3]heptane-6-yl)pyridin-3-yl)amino)pyrimidin-4-yl)- N,N, 1-Trimethyl-1 H -Pyrrole-2-carboxamide; 9-(5-((4-(5-(dimethylcarbamoyl)-1-methyl-1H-pyrrolo-3-yl)pyrimidin-2-yl)amino)pyridin-2-yl)-3,9-diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester; 4-(5-((4-(5-dimethylcarbamoyl)-1-methyl-1H-pyrrolo-3-yl)pyrimidin-2-yl)amino)pyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester 4-(5-((4-(5-dimethylcarbamoyl)-1-methyl-1H-pyrrolo-3-yl)pyrimidin-2-yl)amino)pyridin-2-yl)-1,4-diaza-1-carboxylic acid tert-butyl ester; N,N, 1-Trimethyl-4-(2-((6-(4-methyl-1,4-diazacycloheptane-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)-1H-pyrrolo-2-carboxamide 4-(2-((6-(3,9-diazaspiro[5.5]undecane-3-yl)pyridin-3-yl)amino)pyrimidin-4-yl)-N,N,1-trimethyl-1H-pyrrole-2-carboxamide) N,N 1-Trimethyl-4-(2-((6-(piperazin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)-1 H -Pyrrole-2-carboxamide; 4-(2-((6-(1,4-diaza-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)- N,N, 1-Trimethyl-1 H -Pyrrole-2-carboxamide.

4. The 4-(1) according to claim 2 H (-pyrrole-3-yl)pyrimidine anti-breast cancer compounds, characterized in that... The compound of general formula II or its pharmaceutically acceptable salt, hydrate or solvate, specifically: N,N -Diethyl-1-methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1 H -Pyrrole-2-carboxamide; (1-Methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1 H -pyrrolo-2-yl)(4-methylpiperazin-1-yl) methyl ketone; N -(2-(dimethylamino)ethyl)- N 1-Dimethyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1 H -Pyrrole-2-carboxamide; (1-Methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1 H -pyrrolo-2-yl)(pyrrolidin-1-yl)methyl ketone; (1-Methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1 H -pyrrolo-2-yl)(4-methylpiperidin-1-yl)methyl ketone; (4-(dimethylamino)piperidin-1-yl)(1-methyl-4-(2-((6-morpholinpyridin-3-yl)amino)pyrimidin-4-yl)-1 H -pyrrolo-2-yl)methyl ketone; (4-Methoxypiperidin-1-yl)(1-Methyl-4-(2-((6-morpholinpyridin-3-yl)amino)pyrimidin-4-yl)-1 H -pyrrolo-2-yl)methyl ketone; (1-Methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1 H -pyrrolo-2-yl)(4-(methylsulfonyl)piperazin-1-yl)methyl ketone; (1-Methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1 H -pyrrolo-2-yl)(4-(trifluoromethyl)piperidin-1-yl) methyl ketone; (4,4-Difluoropiperidin-1-yl)(1-methyl-4-(2-((6-morpholinpyridin-3-yl)amino)pyrimidin-4-yl)-1 H -pyrrolo-2-yl)methyl ketone; (1-Methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1 H -pyrrolo-2-yl)(4-(oxetane-3-yl)piperazin-1-yl)methyl ketone; (1-Methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1 H -pyrrolo-2-yl)(4-morpholinopiperidin-1-yl) methyl ketone; (4-Methyl-1,4-diazacycloheptane-1-yl)(1-Methyl-4-(2-((6-morpholinpyridin-3-yl)amino)pyrimidin-4-yl)-1 H -pyrrolo-2-yl)methyl ketone; (1-Methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1 H -pyrrolo-2-yl)(2-oxa-6-azaspiro[3.3]heptane-6-yl) methyl ketone; 4-(1-Methyl-4-(2-(((6-morpholinpyridin-3-yl)amino)pyrimidin-4-yl)-1 H tert-butyl pyrrole-2-carbonyl)piperazine-1-carboxylate; 4-(1-Methyl-4-(2-(((6-morpholinpyridin-3-yl)amino)pyrimidin-4-yl)-1 H tert-butyl 1,4-diaza-1-carboxylic acid (-pyrrole-2-carbonyl)-1,4-diaza-1-carboxylic acid; 9-(1-methyl-4-(2-(((6-morpholinpyridin-3-yl)amino)pyrimidin-4-yl)-1 H -pyrrole-2-carbonyl)-3,9-diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester; (1-Methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1 H -pyrrolo-2-yl)(piperazin-1-yl)methyl ketone; (1,4-diaza-1-yl)(1-methyl-4-(2-((6-morpholinpyridin-3-yl)amino)pyrimidin-4-yl)-1 H -pyrrolo-2-yl)methyl ketone; (1-Methyl-4-(2-((6-morpholinopyridin-3-yl)amino)pyrimidin-4-yl)-1 H -pyrrolo-2-yl)(3,9-diazaspiro[5.5]undecane-3-yl) methyl ketone.

5. The 4-(1) according to claim 1 H (-pyrrole-3-yl)pyrimidine anti-breast cancer compounds, characterized in that... The preparation method of the compounds of general formula I and general formula II specifically includes the following steps: using 4-bromo-1 H Starting with methyl pyrrole-2-carboxylate, the target compounds were obtained through substitution, hydrolysis, amidation, palladium-catalyzed CC coupling, Suzuki-Miyaura coupling, Buchwald-Hartwig coupling, and deprotection reactions, yielding the target compounds represented by general formulas I and II.

6. The 4-(1) as described in any one of claims 1-5 H (-pyrrole-3-yl)pyrimidine anti-breast cancer compounds, characterized in that... The compound can be used in the preparation of antitumor drugs.

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