PYRAZOLOPYRIMIDINE COMPOUND, METHOD OF PREPARATION FOR THE SAME AND ITS APPLICATIONS.
Patent Information
- Authority / Receiving Office
- MX · MX
- Patent Type
- Patents
- Current Assignee / Owner
- SHANGHAI PHARMACEUTICALS HOLDING CO LTD
- Filing Date
- 2021-12-14
- Publication Date
- 2026-05-19
Abstract
Description
PYRAZOLOPYRIMONE COMPOUND, PREPARATION METHOD FOR THE SAME AND ITS APPLICATIONS The present application claims priority of Chinese Patent Application 201910579671.0 filed on June 28, 2019. The content of the Chinese Patent Application is incorporated herein by reference in its entirety. TECHNICAL FIELD OF THE INVENTION The present disclosure relates to a pyrazolopyrimidine compound, a method of preparation thereof and an application thereof. BACKGROUND OF THE INVENTION The cell cycle is closely related to the DNA damage repair process. The cell cycle refers to the entire cell division process, which is divided into two stages: interphase and mitotic (M) phase. The cell cycle checkpoint is a key point for regulating the cell cycle. Its main function is to ensure that each cycle event can be completed in a timely and orderly manner, and to adjust the state of the cell to adapt to the external environment. The main control points of cells are the following: 1) G1 / S control point, which is called R (restriction) point in mammals and controls cells from the static G1 phase to the DNA synthesis phase; 2) S phase checkpoint: whether DNA replication was completed; 3) G2 / M checkpoint: it is the checkpoint that regulates the cell to enter the division stage; 4) mid-late checkpoint: Also called meiotic spindle assembly checkpoint, if the centromere is not properly connected to the meiotic spindle, it will cause cell cycle arrest. If there is an abnormality in some processes of the cell division cycle, such as DNA damage, the checkpoint will detect it in time and start repair. P53 protein is an important protein that regulates the G1 checkpoint, when DNA is damaged, P53 protein prevents cells from entering S phase and activates the DNA repair mechanism, which is very important for maintaining integrity. of the cellular genome. However, since the P53 mutation often exists in tumor cells, making the G1 checkpoint defective, regulation of the cell division cycle in P53-mutated cells depends on the G2 / M checkpoint. . WEE1 kinase is a cell cycle regulatory protein, which can regulate the phosphorylation status of cyclin-dependent kinase 1 (CDK1), thereby regulating the activity of CDK1 and cyclin B complex, realizing cell cycle regulation and playing an important role in regulating DNA damage checkpoints. WEE1 is a key gene in blocking the G2 / M phase, it plays an important role in monitoring and is overexpressed in some cancers, inhibition or underexpression of the WEE1 kinase can trigger a mitotic catastrophe, so inhibitors of the WEE1 kinase have a key role in cancer therapy and have become a focal point for the development of anticancer drugs. International patent applications WO2019037678, WO2019028008, WO2018133829. WO2010098367, WO2010067886, WO2008115742, WO2008115738, WO2007126122, WO2007126128 WO2004007499 and others have disclosed some small molecule WEE1 kinase inhibitors, but there are no WEE kinase inhibitors yet 1 small molecule on the market and there is still a need in the state of the art of developing new WEE1 kinase inhibitors with good anticancer activity and high safety. Content of the Present Invention The technical problem to be solved by the present disclosure is that the existing compounds with inhibitory activity against WEE1 kinase have a unique structure, therefore, the present disclosure provides a pyrazolopyrimidine compound, a method of preparation thereof and an application of the same, and the compound has better inhibitory activity against WEE1 kinase. The present disclosure provides a pyrazolopyrimidine compound represented by formula II, a pharmaceutically acceptable salt thereof, a solvate thereof, a solvate of the pharmaceutically acceptable salt thereof, a metabolite thereof, or a prodrug thereof: ΜΛ / t / ZUZZ / U I0400 where, A is C3-C2o cycloalkyl substituted with one or two R1; X is CH or N; R1is independently halogen, -O1'1, -SR1'2, -CN, -NR1'3R1'4, -C (= O) R1'5, -C (= NR1-S) R1'7, = ÑOR1-9 (where ' refers to the substitution of two hydrogens on the methylene of the cycloalkyl) or C2-C7 alkenyl, C2-C8 aikinyl, C3-C14 cycloalkyl, C3-C!4heterocycloalkyl, CeCw arite or C1-C7 heteroaryl “optionally substituted with one, two or three R1'8; R11 is independently C1-C7 alkyl, C2-C7 alkenyl, C2-C7 aikinyl, C3-Ci4cycloalkyl, C3-C14 heterocycloalkyl, Ce-Cio aryte or C1-C7 heteroaryl' optionally substituted with one, two or three R1'1'1; R1'1'1is independently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl , C6-CiQadio, C1-C7 heteroaryl or ''amino substituted with one or two RMiR1^-1is independently Ci-C? alkyl or C3-C14 cycloalkyl; R1'2 is independently hydrogen, C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Ce-Cio aryl or C1-C7 heteroaryl optionally substituted with one, two or three R1' 2'1; R1·2·' is independently hydrogen, halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, Ci-C? alkoxy, CrC7 alkylthio, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C5-C10 aryl, C1-C7 heteroaryl or amino substituted with one or two R1'2' 1-1»; Ri-2-1-1 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1'3and RV4are independently hydrogen, -S (= O)2R1'3“1, -C (= O) R1'3'2, -C (= NR1' 3-3) NRi-3-5Ri-3-6 _s (= O)2nri-3-?R'-3-8, .Q (= Q)NRi-3-9Ri-3-io0..Cl_C7 a|qu¡|Ojc2.c7alkenyl, C2-C7 alkynyl, C3 -C14 cycloalkyl, C3-C14 heterocycloalkyl, C6-Cio aryl or C1-C7 heteroaryl optionally substituted with one, two or three R1'3'11; or, R1'3 and R1'4 together with the nitrogen atom join to form a C3-C14 heterocycloalkyl optionally substituted with one, two or three r1-3-12; one or more methylenes in the C3-C14 heterocycloalkyl are optionally and independently substituted with an oxygen atom, a sulfur atom, sulfinyl, sulfonyl, carbonyl, vinylidene or -N (R'3R1-3-i3esindependently C1-C7 alkyl or C3 -C14 cycloalkyl; Ri-3-i and Ri-3-2 are independently C1-C7 alkyl, C2-C7 alkenyl, C2-C7alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl or C6-Cio aryl optionally substituted with one or two R1-3-1- '; Ri-3-1-1 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1'3'3 is independently hydrogen, -CN, C1-C7 alkyl, C2-C7alkenyl, C2-C7alkynyl or C3-C14 cycloalkyl; Ri-3-5, ri-3-6<ri-3-7, Ri-3-8)Ri-3-9 and Ri-3-iosonindependently hydrogen, C1-C7 alkyl, C2-C7alkenyl, C2-C7alkynyl or C3-C14 cycloalkyl; or, R1'3'5and R1'3'® together with the nitrogen atom join together to form a C3-C14 heterocycloalkyl optionally substituted with one, two or three R1-3-5-1; one or more methylenes in the C3-C14 heterocycloalkyl are optionally and independently substituted with an oxygen atom, a sulfur atom, sulfinyl, sulfonyl, carbonyl, vinylidene or -N(R13'5'2)-; R1-3-5-1 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1'3'5'2 is independently C1-C7 alkyl or C3-C14 cycloalkyl; or, ΡΛ3'7 and R1-3'8 together with the nitrogen atom join together to form a C3-C14 heterocycloalkyl optionally substituted with one, two or three R13 7-1; one or more methylenes in IVIA / t / ZUZZ / U I0400 the C3-C14 heterocycloalkyl are optionally and independently substituted with an oxygen atom, a sulfur atom, sulfinite, sulfonium, carbonyl, vinylidene or -N (RV3·7·2)-; R1-3-7-1 is independently C1-C7 alkyl or C3-C14 cicioalkyl; R1-3-7-2 is independently C1-C7 alkyl or C3-C14 cicioalkyl; or, R1'3'3 and r-s-io together with the nitrogen atom join together to form a C3-C14 heterocycloalkyl optionally substituted with one, two or three r1-3®-1; one or more methienes in the C3-C14 heterocycloalkyl are optionally and independently substituted with an oxygen atom, a sulfur atom, sulfinite, sulfonium, carbonyl, vinylidene or -N (R1'3'92)-; R1-3-®-1 is independently C1-C7 alkyl or C3-C14 cicioalkyl; R1··3·®·2is independently C1-C7 alkyl or C3-C14 cicioalkyl; R1-3-" is independently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cicioalkyl, C3-C14 heterocycloalkyl, C6-Cio arite, C1-C7 heteroaryl or amino substituted with one or two γ?·-3-τμ”· ri3-n-1is independently C1-C7 alkyl or C3-C14 cicioalkyl; ri-s- izesindependently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cicioalkyl, C3-C14 heterocycloalkyl, Cs-Cio aryl, C1-C7 heteroaryl or amino substituted with one or two R1-312-1; R13-12·' is independently C1-C7 alkyl or C3-C14 cicioalkyl; R1'5is independently hydrogen, -NR^R1·5·2, -01-5-3o C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cicioalkyl, C3-C14 heterocycloalkyl, C6-CYQaryl or C1-C7 heteroaryl optionally substituted with one, two or three R*54; rvs-i and R1-5-2 are independently hydrogen, C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl or C3-C14 cicioalkyl; or, R1'5'1 and R1'5'2 together with the nitrogen atom join together to form a C3-C14 heterocycloalkyl optionally substituted with one, two or three R1-51-1; one or more methylenes in the C3-C14 heterocycloalkyl are optionally and independently substituted with an oxygen atom, a sulfur atom, sulfinite, sulfonium, carbonyl, vinylidene or -N(R1-5-1-2)-; R1-5-1-1 is independently C1-C7 alkyl or C3-C14 cicioalkyl; R1·5'1'2is independently C1-C7 alkyl or C3-C14 cicioalkyl; R1'5'3 is independently hydrogen, C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cicioalkyl, C3-C14 heterocycloalkyl, Ca-Cw arite or C1-C7 heteroaryl; R1'5·4is independently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cicioalkyl, C3-C14 heterocycloalkyl , C6-Ci0aryl, C1-C7 heteroaryl or amino substituted with one or two R1'5'4·1; r1·5'4·1is independently C1-C7 alkyl or C3-C14 cicioalkyl; Rrses independently hydrogen, -CN, -OH or C1-C7 alkyl, C2-C7 alkenium, C2 IVIA / t / ZUZZ / U I0400 C7alkynyl, C3-C14 cycioalkyl, C3-C14 heterocycloalkyl, C6-Ci0arite or C1-C7 heteroaryl optionally substituted with one, two or three R1'6'1; R1'84isindependently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C2-C7alkenite, C2-C7alkynyl, C3-C14 cicioalkyl, C3-C14 heterocycloalkyl, C6-Cio arite , C1-C7 heteroaryl or amino substituted with one to two R1'644; R1-614 is independently C1-C7 alkyl or C3-C14 cicioalkyl; R1'7is independently hydrogen, -OR1'74, -NR1'7'ZR1·7'3o C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycioalkyl, C3-C14 heterocycloalkyl, Cs-Cw arite or C1-C7 heteroaryl” optionally substituted with one, two or three R! 7 4; Is R1·74 independently hydrogen, C1-C7 alkyl, C2-C7alkenite, C2-C7 alkynyl, C3-C14 cicyoalkyl, C3-C14 heterocycloalkyl, C5-Cy0arite or CrC? heteroaryl; R17'2 and R1·7'3 are independently C1-C7 alkyl, C2-C7alkenyl, C2-C7 alkynyl or C3-C14 cictoalkyl; or, R1'7'2 and R'-7'3 together with the nitrogen atom join together to form a C3-C14 heterocycloalkyte optionally substituted with one, two or three R1'·7'24; one or more mephylenes in the C3-C14 heterocycloalkyl are optionally and independently substituted with an oxygen atom, a sulfur atom, suifiniium, sulfoniium, carbonyl, vinylidene or -N (R1'7·2'2)-; R1-7-24is independently Ci-C? alkyl or C3-C14 cycloalkyl; r1-7-2-2is independently C1-C7 alkyl or C3-C14 cictoalkyl; R1·7'4is independently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C2-C7alkenyl, C2-C7alkynyl, C3-Cm cictoalkyl, C3-C14 heterocycloalkyl, C6 -Cy0arite, C1-C7 heteroaryl or amino substituted with one or two R1'7'44”; R17'44 is independently C1-C7 alkyl or C3-C14 cicioalkyl; R1'8is independently oxo, halogen, -OH, amino, mercapto, cyano, Ci-C7alkyl, Ci-C7alkoxy, Ci-C7alkylthio, C2-C7alkenite, C2-C7alkynyl, C3-C14 cictoalkyl, C3-C14 heterocycloalkyl, C6-Ci0aryte , Ci-C7heteroaryl or amino substituted with one or two R1·8·1 is independently C1-C7 alkyl or C3-C14 cictoalkyl; R1'3 is independently hydrogen or C1-C7 alkyl; R2es -O24, cyano, carboxite; or C2-C7 alkyl, C3-C14 cicioalkyl or C3-C14 heterocycloalkyl optionally substituted with one, two or three R2'2; R24 is Ci-C7alkyl, C2-C7alkenyl, C2-C7alkynyl, C3-C14 cicyoalkyl, C3-C14 heterocycloalkyl, Ce-Cw arite or C1-C7 heteroaryl; R24 is independently halogen, hydroxyl, amino, C1-C7 alkyl, C:-C7alkoxy, C3Cu cictoalkyl or C3-C14 heterocycloalkyl; In any of the above cases, the heteroatoms in the C3-Cm heterocycloalkyl, Ci-C7heteroaryl are independently selected from one or more of boron, silicon, oxygen, IVIA / t / ZUZZ / U I0400 s sulfur, setenium, nitrogen and phosphorus; the number of heteroatoms is independently 1,2,3 or 4. In a certain scheme, some substituents in the pyrazolopyrimidine compound represented by formula II, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof or the prodrug thereof may further have the following definitions, and the definitions of substituents not involved below are those described in any of the above schemes (hereinafter referred to in a given scheme): When A is C3-C20 cidoalkyl substituted with one or two R1, the C3-C20 cycloalkyl is, for example, C3-C20 monocyclic cycloalkyl, C3-C20 spiro cycloalkyl, C3-C20 fused cycloalkyl or bridged C3-C20 cycloalkyl. C3-C20 monocycyic cidoalkyl is, for example, C3-C3 monocytic cidoalkyl, for example ciciopropyl, dclobutyl, cidopentyl or cyclohexiium, for example cyclohexiium. C3-C20 bridged cycloalkyl is, for example, C5-C8 bridged cycloalkyl, e.g. In a certain scheme: When A is C3-C20 cycloalkyl substituted with one or two R1, the C3-C20 cycloalkyl is, for example, C3-C20 saturated cycloalkyl. In a certain scheme: When A is C3-C20 cycloalkyl substituted by a R1, the A is for example R! or R1. and R' is 1:1. In a certain scheme: When R1 is independently Cs-Cu heterocycloalkyl, the C3-C14 heterocycloalkyl is, for example, C3-C14 monocyclic heterocycloalkyl, C3-C14 spiro heterocycloalkyl, C3-C14 fused heterocycloalkyl or C3-C14 bridged heterocycloalkyl. C3-C14 monocyclic heterocycloalkyl is, for example, C3-C9 monocyclic heterocycloalkyl having one or two heteroatoms selected from one or two of N, O and S, for example, C3-C5 monocyclic heterocycloalkyl having one or two heteroatoms selected from one or two of N, O and S”, for example, “C3-C5 monocyclic heterocycloalkyl that has one or two heteroatoms selected from one or two of N, O and S and that is connected to a benzene ring by an atom of nitrogen, for example, azetidinyl, morpholinyl, piperidinyl or piperazinyl. ww I □ - hL C > Azetidinyl is for example. The morpholinium is for example u. piperidinyl is for example or H. Piperazinyl is for example H In a certain scheme: When R1 is independently C3-C14 heterocycloalkyl, the heteroatom of the C3-C14 heterocycloalkyl cannot be substituted. In a certain scheme: When R1 is independently C3-C14 heterocycloalkyl, the methylene in the C3-C14 heterocycloalkyl cannot be substituted. In a certain scheme: When R! is independently C3-Cu heterocycloalkyl substituted by a R1'8, the C3-C14 heterocycloalkyl is, for example, C3-C14 monocyclic heterocycloalkyl, C3-Cuspiro heterocycloalkyl, C3-C14 fused heterocycloalkyl or bridged C3-C14 heterocycloalkyl. C3-C14 monocyclic heterocycloalkyl is, for example, C3-C9 monocyclic heterocycloalkyl having one or two heteroatoms selected from one or two of N, O and S, for example, “C3-C5 monocyclic heterocycloalkyl having one or two heteroatoms selected of one or two of N, O and S”, for example, C3-C5 monocyclic heterocycloalkyl having one or > π N C N two heteroatoms selected from one or two of N, O and S and connected to a benzene ring by a nitrogen atom, for example, azetidinyl, morpholinyl, piperidinyl or piperazinyl. □ IXJ Q Azetidinyl is for example. Morpholinyl is for example or . The piperidinüo I »AAÍV I v*VWI LKi A ÓO i J NN is for example Ή0h . Piperazinyl is for example H. In a certain scheme: When R1 is independently C3-C14 heterocycloalkyl substituted by a Rvs, the heteroatom of the C3-C14 heterocycloalkyl cannot be substituted except R1'8. In a certain scheme: When R1 is independently C3-C14 heterocycloalkyl substituted by a R1-8, the methylene in the C3-C14 heterocycloalkyl cannot be substituted. In a certain scheme: When R1 is independently C3-C14 heterocycloalkyl substituted by a R1'8, the ΓA Cs-Cíí heterocycloalkyl may perhaps be substituted by an R·-8 In a certain scheme: When R1'3and RMare independently C1-C7 alkyl, the C-C? alkyl is, for example, C<-C3alkyl, for example methyl, ethyl, n-propyl or isopropyl. In a certain scheme: When R13'1 is independently C1-C7 alkyl, the C1-C7 alkyl is, for example, C1C3alkyl, for example methyl, ethyl, n-propyl or isopropyl. In a certain scheme: When R1'32 is C3-C14 cycloalkyl, the C3-C14 cycloalkyl is, for example, C3-C14 monocyclic cycloalkyl, for example C3-C6 monocyclic cycloalkyl, for example cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, for example cyclopropyl. In a certain scheme: When R1'3-2 is C3-C14 cycloalkyl, the C3-C14 cycloalkyl is, for example, C3-C14 > π N c N saturated cycloalkyl. In a nutshell: When RV5 is independently C3-C14 heterocycloalkyl, C3-C14 heterocycloalkyl is, for example, C3-C14 monocyclic heterocycloalkyl, C3-C14 spiro heterocycloalkyl, C3-C14 fused heterocycloalkyl or C3-C:4 bridged heterocycloalkyl. C3-C14 monocyclic heterocycloalkyl is, for example, “C3-C9 monocyclic heterocycloalkyl having one or two heteroatoms selected from one or two of N, O and S, for example, C-j-Cs monocyclic heterodcloalkyl having one or two heteroatoms selected of one or two of N, O and S”, for example, C3-C5 monocyclic heterocycloalkyl which has one or two heteroatoms selected from one or two of N, O and S” and which is connected to a benzene anyl by one atom of nitrogen, for example, azetidinylc. Z] •v Azetidinyl is for example Λ In a certain scheme: When Ri Ses independently C3-C14 heterocycloalkyl, the heteroatom of the C3Cu heterocycloalkyl cannot be substituted. In a certain scheme: When R15 is independently C3-C14 heterocycloalkyl, the methylene in the C3-C14 heterocycloalkyl cannot be substituted. In a certain scheme: When R151 and R15'2 are independently C1-C7 alkyl, the C1-C7 alkyl is, for example, C1-C3 alkyl, for example methyl, ethyl, n-propyl or isopropyl. In a certain scheme: When R1'5'1 and R1'5'2 are independently C3-C14 cycloalkyl, the C3-Cm cycloalkyl is, for example, C3-C14 monocyclic cycloalkyl, C3-C14 spiro cicioalkyl, C3-C14 fused cycloalkyl or bridged C3-C14 cycloalkyl . C3-C14 monocyclic cycloalkyl is, for example, C3-C6 monocyclic cycloalkyl, for example cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, for example cyclobutyl, cyclopentyl or cyclohexyl. The C3-C14 bridged cycloalkyl is. for example, C5-C3 bridged cycloalkyl. by In a certain scheme: When R1'5-1 and R1-5-2 are independently C3-C14 cycloalkyl, the C3-C14 cycloalkyl is, for example, C3-Cn saturated cycloalkyl. In a certain scheme: When R1-5'3 is independently C1-C7 alkyl, CrC7alkyl is, for example, C1C3alkyl, for example methyl, ethyl, n-propyl or isopropyl. In a certain scheme: When R1'9 is independently Ci-C7alkyl, the C1-C7 alkyl is, for example, Cr C3alkyl, for example methyl, ethyl, n-propyl or isopropyl. In a certain scheme: When R2 is C2-C7 alkyl optionally substituted with one, two or three R2 2, the C2-C7 alkyl is, for example, C2-C4 alkyl, for example ethyl, n-propyl, isopropyl, π-butyl, i sobutyl, sec -butyl or tert-butyl, for example isopropyl. In a certain scheme: When R2 is C2-C7 alkyl substituted by a R22, R22 is hydroxyl; the C2-C7alkyl OH ΜΛ / t / ZUZZ / U I0400 replaced by an R:·· is for example 1. In a certain scheme: When R2 is C3-C14 heterocycloalkyl optionally substituted with one, two or three R2'2, the C3-C14 heterocycloalkyl is, for example, C3-C14 monocyclic heterocycloalkyl, C3-C14 spiro heterocycloalkyl, C3-C14 fused heterocycioalkyl or C3-C14 heterocycloalkyl bridged. C3-Ci4 monocyclic heterocycloalkyl is, for example, C3-C9 monocyclic heterocycloalkyl having one or two heteroatoms selected from one or two of N, O and S, for example, C3-C5 monocyclic heterocycloalkyl having one or two heteroatoms selected from one or two of N, O and S, for example, C3-C5 monocyclic heterocycloalkyl having one or two heteroatoms selected from one or two of N, O and S” and which is connected to a benzene ring by a nitrogen atom , for example, oxetanil. Morphoylinyl oxetanyl is, for example, oxetan-3-yl. In a certain scheme: When R2 is C3-C14 heterocycloalkyl optionally substituted with one, two or three R2 2, the heteroatom of the C3-C14 heterocycloalkyl cannot be substituted except R22. In a certain scheme: When R2 is C3-C14 heterocycloalkyl optionally substituted with one, two or three R2 2, the methylene in the C3-C14 heterocycloalkyl cannot be substituted. In a certain scheme: When R2 is C3-C14 heterocycloalkyl substituted by an R22. R2'2is halogen or _____ ι Γ ι $ Γ~ ι π π hydroxyl; the C3-C14 heterocycloalkyl substituted by a R2'2 is for example oh or f In a certain scheme: The proportion of each isomer in the pyrazolopyrimidine compound represented by formula II may be the same, for example, racemate. In a certain scheme: The atoms of the pyrazolopyrimidine compound represented by formula II, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof or the prodrug thereof may all exist in their natural abundance . In a certain scheme: A is C3-C20 cycloalkyl substituted by an R1. In a certain scheme: A is* v , 7— / , * v or 7— / replaced by one or two R1”. In a certain scheme: JVVV j 1* .ΛΛΛ / Ψ A is R1 or R1. In a certain scheme: R1 is independently halogen, -CN, -NR'^R1'4, -C (= O) R15, -C (= NR1-6) R17, = ÑOR1'8o C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Cs-Cw adio or C1-C7 heteroaryl optionally substituted with one, two or three R1'8. R13and R14are independently hydrogen, -S (= O)2R1'3'1, -C (= O) R1'3'2, -C (= NR13'3) NR13SR1-36, -S (= O^RW'3 ·8, -C (= O) NR^^R1310o C1-C7 alkyl, C3-Ci4cycloalkyl, C3-C14 heterocycloalkyl, Cs-Cw aryl or C1-C7 heteroaryl optionally substituted with one, two or three R1'3'11; ^1-3-1 and pi-3-2 are independently C1-C7 alkyl, C3-C14 cycloalkyl, C3-Ci4heterocycloalkyl or Cs-Cw aryl optionally substituted with one or two R1-3-11"; ri-3-μesindependently C1-C7 alkyl; R1'3'3is independently hydrogen; R1'3'5, R1'3'6, R137, R1'3'8, R1'3'9 and R1·313 are independently hydrogen, C1-C7 alkyl or C3-Cu cycloalkyl; R1'3'11is independently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Cs-Cio aryl, C1-C7 heteroaryl or amino substituted with one or two ri-3-h-i»;Ri-3-n-iesindependently C1-C7 alkyl or C3-C14 cycloalkyl; R1·5is independently hydrogen, -NR1'5'1R1·5·2, -O1·5·3or C1-C7 alkyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C6-Cy0adium or C1-C7 heteroaryl optionally substituted with one , two or three R1-5-4; ^1-5-1 and Ri-s-2 are independently hydrogen, C1-C7 alkyl or C3-C14 cycloalkyl; R1'5'3 is independently hydrogen, C1-C7 alkyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Ce-Cio aryl or C1-C7 heteroaryl; R1'5·4is independently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Cs-Ci0 aryl, C1-C7 heteroaryl or “amino substituted with one or two R1-5-4-1”; ri 3·4·ι is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1 is independently hydrogen, -CN, -OH; R1'7is independently hydrogen, -NR1·7·^1·7·3; Ri-7-2 and ^1-7-3 are independently C1-C7 alkyl or C3-C14 cycloalkyl; or, R1'7'2 and R1'7'3 together with the nitrogen atom join together to form a C3-C14 heterocycloalkyl optionally substituted with one, two or three r1-7·2-1; one or more methylenes in the C3-C14 heterocycloalkyl are optionally and independently substituted with an oxygen atom, a sulfur atom; R17·2·1 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1-8is independently oxo, halogen, -OH, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Cs-Ci0aryl, C1-C7 heteroaryl or amino substituted with one or two R1-8·1; R131 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1'9 is independently hydrogen or C1-C7 alkyl. In a certain scheme: R1 is independently halogen, -CN, -ΝΡ^Ρύ4, -C (= O) R1-5, -C (= NR1'6) R1'7 or C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C6-Ci0aryl or C1-C7 heteroaryl optionally substituted with one, two or three R18; R1'3and R1-4are independently hydrogen, -S (= O)2R1'3'1, -C (= O) R1'3'2, -C (= ΝΡΛ 3-3) NR1-3-5R1-3- 6 _S 0)aNR1-3-7R1-3-8 _CQ)NR1-3-9R1-3-W q CrC7a^Ui|OiC3-C14 C! Cl03 lq UI i O, C3-C14 heterocycloalkyl, Ce-Cío aryl or C1-C7 heteroaryl optionally substituted with one, two or three R1'3'11; Ri-3-i and Ri-3-2sor (independently C1-C7 alkyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl or Ce-Cio aryl optionally substituted with one or two R1-3-1-1; R1-3-1 -1 is independently C1-C7 alkyl; R1'3'3is independently hydrogen; R1-3-5,Ri-3-e R1-3-7, ri-3-8, ri-3-9and Ri-3-iones are independently C1-C7 alkyl or C3-Ci4cycloalkyte; Rl 3 iies independently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C3-C14 cycloalkyl, C3-Cu heterocycloalkyl, Cs-Ci0arite·, C1-C7 heteroaryl or amino substituted with one or two ri-j-h-:esindependently C1-C7 alkyl or C3-C14 cycloalkyl; R1'5is independently hydrogen, -NR1·5^1-5 2, -O15 3o C1-C7 alkyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Cs-Cw arite or C1-C7 heteroaryl 'optionally substituted with one, two or three R1'5'4; R1-5-1 and Ri-5-2 are independently hydrogen, C1-C7 alkyl or C3-C!4cycloalkyl; R15'3 is independently hydrogen, C1-C7 alkyl, C3-Ci4cycloalkyl, C3-Ci4heterocycloalkyl, C6-Cio aryte or C1-C7 heteroaryl; r-i-5-4esindependently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C3-Ci4cycloalkyl, C3-Ci4heterocycloalkyl, Cs-Cio arite, C1-C7 heteroaryl or substituted amino with one or two R1'5'4'1”; R1-5-4-1 is independently C1-C7 alkyl or C3-Ci4cycloalkyl; R1-5is independently hydrogen, -CN, -OH; R1'7is independently hydrogen, -NR^'^R1'7'3; R1-7-2 and ri-7-3 are independently C1-C7 alkyl or C3-C14 cycloalkyl; or, R1·7'2 and R77'3 together with the nitrogen atom join together to form a C3-C14 heterocycloalkyte optionally substituted with one, two or three R1-7 2-1; one or more methylenes in the C3-Ci4heterocycloalkyte are optionally and independently substituted with an oxygen atom, a sulfur atom; R1-7-2-1 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1's independently halogen, -OH, amino, mercapto, cyano, C1-C7 alkyl, C1C7 alkoxy, C1-C7 alkylthio, C3-Ci4 cycloalkyl, C3-Ci4 heterocycloalkyl, Cs-Cio arite, C1-C7 heteroaryl or substituted amino with one or two R1'8'1”; R1-8-1 is independently C1-C7 alkyl or C3-Ci4 cycloalkyl. In a certain scheme: R1 is independently cyano, halogen, -NR1'3R1'4, -C (= O) R1'5, -C (= NR1'6) R1'7, = ÑOR1'3, C1-C7 heteroaryl or optionally substituted C3-Ci4heterocycloalkyl with an R1'8”. In a certain scheme: R1 is independently cyano, halogen, -NR1'3R1'4, -C (= O) R15, -C (= NR1'e) R1'7, C1-C7 heteroaryl or C3-Ci4heterocycloalkyl. In a certain scheme: R1 is -CN, -NR!3RM, -C (= O) R'f - ÑOR1'9, or C3-C14 heterocycloalkyte optionally substituted with an R18”. In a certain scheme: R1is independent -NR^R1'4, -C (= O) R1'5o C3-C14 heterocidoalkyl. In a certain scheme: R1-3and r1-4are independently hydrogen, -S (= O^R1'3'1, -C (= O) R1'3'2, -C (= NRV3-3)NR1-3-5R1-3-6 !qa|qUn0;Ri-3-i and Ri-3-2 are independently C1-C7 alkyl, or C3-C14 cycloalkyl; R1'3'3is hydrogen; R1·35yRi-3-sonhydrogen. In a certain scheme: R1-3 and Ri-4 are independently hydrogen, -S (= O^R1'3'1o Ci-C? alkyl; R1-3-1 is independently C1-C7 alkyl. In a certain scheme: R1'5is independent -NR^R1'5'2, -O'·5·3o C3-C14 heterocidoalkyl; R1'5'1 and R1'5'2 are independently hydrogen, C1-C7 alkyl or C3-C14 cycloalkyl; R1'5'3 is independently hydrogen or C1-C7 alkyl. In a certain scheme: R1-5is independent -NR1·5·^1·5'2, -O1'5'3o C3-C14 heterocidoalkyl; R1'5'1 and R1'5'2 are independently hydrogen, C1-C7 alkyl or C3-C14 dcloalkyl; R1'5'3is hydrogen. In a certain scheme: R'-3is independently oxo. In a certain scheme: R1'9 is independently hydrogen or C1-C7 alkyl. In a certain scheme: R2 is “C2-C7 alkyl, C3-C14 cycloalkyl or C3-C14 heterocidoalkyl optionally substituted with one, two or three R2'2; R2-2is independently halogen or hydroxyl. In a certain scheme: R2 is C2-C7 alkyl or C3-Cm heterocidoalkyl substituted by a R2'2”; R2'2is halogen or hydroxyl. In a certain scheme: R2 is C2-C7 alkyl or C3-C14 heterocidoalkyl substituted by a R2'2”; R2 2is hydroxyl. In a certain scheme: ΜΛ / t / ZUZZ / U I0400 > π N C N In a certain scheme: X is Ν. In a certain scheme: R1es = NORi S; R13 is independently hydrogen or C1-C7 alkyl. In a certain scheme: R1'3'6, R1'3, R1·'8, R·'-'9, and R1-3-10 are hydrogen. In a certain scheme: '—' replaced by one or two R1'; X is CH or N; R1 is independently halogen, -CN, -NR^R1·4, -C (= O) R1'5, -C (= NR·-6) R1'7, = ÑOR1'9o C3-C14 cycloalkyl, C3-C14 heterocycloalkyl , Cs-Cw aryl or C1-C7 heteroaryl optionally substituted with one, two or three R! 8. Rr3and Ri-4 are independently hydrogen, -S (= O)2R1'3'1, -C (= O) R1·3'2, -C (= NRr3-3) NR1 -3-5R1-3-6 _S (=0)^1-3-7^-3-8, _Cz=Q)NR1-3-9R1-3-10 θa|quj|0 C3.Cl4 CiC|0a!quÍl0, C3-C14 heterocycloalkyl, Ce-Cw aryl or C1-C7 heteroaryl optionally substituted with one, two or three R1'3·11; Ri-3-i and Ri-3-2 are independently C1-C7 alkyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl or C5-Ci0aryl optionally substituted with one or two r1-3-i-vri-3-me, independently C1-C7 alkyl. ; R1'3'3is independently hydrogen; R1'3'5, RV3'S, R1'3'7, R1'3'8, R1'3'9 and R1-3-10 are independently hydrogen, C1-C7 alkyl or C3-C14 cycloalkyl; R1'3 iies independently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, CS-C1Uaryl, C1-C7 heteroaryl or amino replaced with one or two ri-3-^-·”; Ri-3-11-1 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1'5is independently hydrogen, -MR^R1·5-2, -OV5“3o C1-C7 alkyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C6-Ci0aryl or C1-C7 heteroaryl optionally substituted with one, two or three R1'5'4; r-i-5-i and ri-s-2are independently hydrogen, CrC? alkyl or C3-C14 cycloalkyl; R1'5'3 is independently hydrogen, C1-C7 alkyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Ce-Cio aryl or C1-C7 heteroaryl; R1'5'4is independently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Cs-Cio aryl, C1-C7 heteroaryl or amino substituted with one or two r1-5-4-1”; ri-5-4-i is independently C1-C7 alkyl or Cs-Cu cycloalkyl; R1's independently hydrogen, -CN, -OH; R1'7is independently hydrogen, -NR1·7·^1·7·3; R1·72and R··7·3are independently C1-C7 alkyl or C3-C14 cycloalkyl; or, R1'7'2 and R1'7'3 together with the nitrogen atom join together to form a C3-C14 heterocycloalkyl optionally substituted with one, two or three r1-'^1; one or more methienes in the C3-C14 heterocycloalkyl are optionally and independently substituted with an oxygen atom, a sulfur atom; R1-7 21 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1Ses independently oxo, halogen, -OH, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C3-Ci4 cycloalkyl, C3-C14 heterocycloalkyl, Cs-Cw aryl, C1-C7 heteroaryl or amino substituted with one or two R1-®-1”; R1-®-1 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1'3 is independently hydrogen or C1-C7 alkyl; R2 is C2-C7 alkyl, C3-C14 cycloalkyl or C3-C14 heterocycloalkyl optionally substituted with one, two or three R2'2; R2'2is independently halogen or hydroxyl; In any of the above cases, the heteroatoms in the C3-C14 heterocycloalkyl, Ci-C? heteroaryls are independently selected from one or more of boron, silicon, oxygen, sulfur, setenium, nitrogen and phosphorus; the number of heteroatoms is independently 1,2,3 or 4. In a certain scheme: A is C3-C20 cycloalkyl substituted with one or two R1; Xes CHoN; R1 is independently cyano, halogen, -NR^R1'4, -C (= O) R15, -C (= NR1'6) R1'7, = ÑOR1'8, C1-C7 heteroaryl or C3-C14 heterocycloalkyl optionally substituted with an R·'8; ri-3 and 4are independently hydrogen, -S (= O^R1'31, -C (= O) R1·32, -C (= NR!3-3)NRi-3-5Ri-3-5ocrC7 a|quHo; R1-3-1 and Ri-3-2 are independently C1-C7 alkyl, or C3-C14 cycloalkyl; R1'3'3is hydrogen; Ri-3-5 and Ri-3-5 are hydrogen; R1'5is independent -NR1'5·^'5·2, -Ob5'3o C3-C14 heterocycloalkyl; R1-5'1and R1'5'2are independently hydrogen, C.-C? alkyl or C3-C14 cycloalkyl; R1'5'3 is independently hydrogen or C1-C7 alkyl; R13is independently oxo; R1'3is independently hydrogen □ C1-C7 alkyl; R2 is C2-C7 alkyl or C3-C14 heterocycloalkyl substituted by a R2'2”; R22 is halogen or hydroxyl. In a certain scheme: A is C3-C20 cycloalkyl substituted by an R1; X is CH or N; R1es O) R1'5, ÑOR1'3, or heterocycloalkyl 'Optionally substituted with an R1'8; R1'3and Ri-4 are independently hydrogen, -S (= O)2R1'3“1, -C (= O) R1'3'2, -C (= NR1'3-3) NRi-3-5Ri- 3-e0 Cre7alkyl; R1·31 and ri-3-2 are independently C1-C7 alkyl, or C3-C14 cycloalkyl; R1-3'3is hydrogen; r!-3-5 andRi-3-3arehydrogen; R1Ses -NR1'5'^1·5·2, -O1·53o C3-Cu heterocidoaikyl; Ri-5-i and Ri-5-2 are independently hydrogen, C1-C7 alkyl or C3-C14 cycloalkyl; R1'5'3 is independently hydrogen or C1-C7 alkyl; R18is independently oxo; R1'3 is independently hydrogen or C1-C7 alkyl; R2 is C2-C7 alkyl or C3-C14 heterocycloalkyl substituted by a R2'2”; R2'2is hydroxyl. In a certain scheme: A is C3-C20 cycloalkyl substituted by an R1; X is CH or N; R1 is -CN, -ΝΡ'Μ, -C (= O) R!í = ÑOR'-9, or C3-C14 heterocycloalkyl optionally substituted with a R1'8; R13and Ri-4 are independently hydrogen, -S (= O^R1'31, -C (= O) R1'3'2, -C (= NR1' 3-3) NR1-3-5R1-3-6 qCrC ?alquÜO; R1-3- and Ri-3-2 are independently C1-C7 alkyl, or C3-C14 cycloalkyl; R1-3-3hydrogen; R1-3-5 andRi-3-sonhydrogen; R1'5is -NR1'5'1R1·5·2, -O1'5'3o C3-Cu heterocycloalkyl; Ri-5-i and ri-5-2 are independently hydrogen, C1-C7 alkyl or C3-C14 cycloalkyl; R1'5'3 is hydrogen; R1'3is independently oxo; R1'3 is independently hydrogen or C1-C7 alkyl; R2 is C2-C7 alkyl or C3-C14 heterocycloalkyl substituted by a R2'2”; R2'2 is hydroxyl. In a certain scheme: ! A is R1 or R1; X is CH or N; R1 is -CN, -NR13R1·4, -C (= O) R1'5, = ÑOR13, or C3-C14 heterocycloalkyl 'Optionally substituted with a R1'8; R1-3and RV4are independently hydrogen, -S (= O^R1'3'1, -C (= O) R1'3'2, -C (= NR1' 3-3)NR1-3-5R1-3-Bi or CrC?alkyl; R13'1yri-3-2are independently C1-C7 alkyl, or C3-C14 cycloalkyl; R13'3 is hydrogen; R1*35andRi-3-6arehydrogen; R1'5is -NR1-5-^'-5-2, -O1'5'3o C3-C14 heterocycloalkyl; R1'5'1 and R1'5'2 are independently hydrogen, C1-C7 alkyl or C3-C14 cycloalkyl; R1'5'3 is hydrogen or C1-C7 alkyl; R18is independently oxo; R1'3is independently hydrogen or C1-C7 alkyl: R2 is C2-C7 alkyl or C3-C14 heterocycloalkyl substituted by a R2'2”; R2'2 is hydroxyl. In a certain scheme: Yo A is R1 or R1; X is CH or N; R1 is independently -CN, -NR^R1'4, -C (= O) R1'5, = ÑOR1'9, or C3-C14 heterocycloalkyl optionally substituted with a R1-8; ri-3 and Ri-4 are independently hydrogen, -S (= O^R1'3'1, -C (= O) R1'3'2, -O (= NR1' 3-3) NR1'3'5R1'3' b, or C1-C7 alkyl; R1'3'1 and R1'3'2 are independently C1-C7 alkyl, or C3-C14 cycloalkyl; R1·3'3is hydrogen; Ri-3-5 and Rt-3-6 are hydrogen; R1'5 is independent -NR1'5'^1'5·2, -O1'5-3, or C3-C14 heterocycloalkyl; Ri-5-i and Ri-s-2 are independently hydrogen, C1-C7 alkyl, or C3-C14 cycloalkyl: R1'5'3 is independently hydrogen or C1-C7 alkyl; RI Ses independently oxo; R1'9 is independently hydrogen or C1-C7 alkyl; OH ।—O ।—o . m14~p R2es i , OH or F . In a certain scheme, the pyrazolopyrimidine compound represented by the formula QQfrQ I 0 / 7707 / 3 / ΥΙΛ II may be a pyrazolopyrimidine compound represented by formula I: where, A is C3-C20 cycloalkyl substituted with one or two R1; R1is independently halogen, -O'-1, -SR1'2, -CN, -NR^R1*·, -C (= O) R1'5, -C (= NR13) R1'7o C2-C7 alkenyl, C2 -C8alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Cs15 Cw aryl or C1-C7 heteroaryl optionally substituted with one, two or three R1-8; R1'1 is independently C1-C7 alkyl, C2-C7 alkenyl, C2-C7alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C6-Cio aryl or C1-C7 heteroaryl optionally substituted with one, two or three R1'1'1 : R1'1'1is independently halogen, hydroxyl, amino, mercapium, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Ce-Cw aryl, C1-C7 heteroaryl or amino substituted with one or two Ri-i-i-i;ri1“1'1is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1'2 is independently C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Ce-Cio aryl or C1-C7 heteroaryl optionally substituted with one, two or three R12'1 ; R1'2·1is independently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C2-C7alkenyl, C2-C7alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Ce -Cío aryl, C1-C7 heteroaryl or “amino substituted with one or two ri-2-ι-ι”; ri2'11 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1'3and R1'4are independently hydrogen, -S (= OjzR1'3'1, -C (- O) R1'3'2, -C (= NR1'3-3) NR^^R1'3'6, -S (= O)2NR1'3-7R1-3-8, -C (= O) NR1'3^1'3·10o C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl , C3-C14 heterocycloalkyl, Ce-Cw aryl or C1-C7 heteroaryl optionally substituted with one, two or three R'-3-11; or, R1'3 and R1'4 together with the nitrogen atom join to form a C3-C14 heterocycloalkyl optionally substituted with one, two or three R1-3'12; one or more methylenes in the C3-C14 heterocycloalkyl are optionally and independently substituted with an oxygen atom, a sulfur atom, sulfinyl, sulfonium, carbonite, vinylidene or -N(R1'3'13)-; R1-3-i3 is independently a CpCz alkyl or Cs-Cr cycloalkyl; R1'3-' and Ri-3-2 are independently C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl or C5-Ci0 aryte optionally substituted with one or two R' -3-1-1; Ri-3-1-1 is independently Ci-C? alkyl or C3-Cr cycloalkyl; R1'3'3is independently hydrogen, -CN, C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl or C3-C14 cycloalkyl; ri-3-5, ri-3-6)ri-3-7¡ri-3-8<ri-3-9 and Ri-3-w are independently C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl or C3-C14 cycloalkyl; or, R1'3'5and R'-3-s together with the nitrogen atom join together to form a C3-Cr heterocycloalkyl optionally substituted with one, two or three R1'3'5·1; urt0 0 m¿smetienes in the C3-C14 heterocyctoalkyl are optionally and independently substituted with an oxygen atom, a sulfur atom, sulfinyl, sulfonium, carbonite, vinylidene or -N (R73'5'2)-; R1'3-5-1 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1'3'5'2 is independently C1-C7 alkyl or C3-C14 cycloalkyl; or, R1'3'7 and R1-3'8 together with the nitrogen atom join to form a C3-C14 heterocycloalkyl optionally substituted with one, two or three R1-3-7-i;υηο 0 m^s methylenes in the C3-C14 heterocyctoalkyl are optionally and independently substituted with an oxygen atom, a sulfur atom, sulfinyl, sulfonium, carbonite, vinylidene or -N(R1·3·7'2)-; R1'3'7'1 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1-3·7-2 is independently C1-C7 alkyl or C3-C14 cycloalkyl; or, R1'3'9 and R'-3'10 together with the nitrogen atom join to form a C3-C14 heterocycloalkyl optionally substituted with one, two or three R1·3·91; one or more methylenes in the C3-C14 heterocyctoalkyte are optionally and independently substituted with an oxygen atom, a sulfur atom, sulfinyl, sulfonium, carbonyl, vinylidene or -N(R'-3-9-2)-; R'-3-®-1 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R13·9·2is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1-3-nesindependently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C2-C7 alkenyl, C2-C? alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Cs-Cw aryl, C1-C7 heteroaryl or amino substituted with one or two R1-3--!”; ri3-11-1 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R73'2is independently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocyctoalkyte, C6 -Ci0arite, C1-C7 heteroaryl or amino substituted with one or two r / ·3·^·!”; ri3·12-1is independently C1-C7 alkyl or C3-C14 cycloalkyl; R75is independently hydrogen, -NR'^R1'52, -O15'3o C1-C7 alkyl, C2-C7 IVIA / t / ZUZZ / U I0400 alkenyl, C2-C7alkynyl, C3-C14 cicioalkyl, C3-C14 heterocycloalkyl, Cs-Cw arite or C1-C7 heteroaryl optionally substituted with one, two or three RV5'4; R1'5-' and R1-5'2 are independently hydrogen, C1-C7 alkyl, C2-C7alkenyl, C2-C7 alkynyl or C3-C14 cycloalkyl; or, R1'5'1 and R1'5'2 together with the nitrogen atom join together to form a C3-C14 heterocycloalkyl optionally substituted with one, two or three Ri-5--i; one or more methylenes in the C3-C14 heterocycloalkyl are optionally and independently substituted with an oxygen atom, a sulfur atom, sulfinyl, sulfonyl, carbonyl, vinylidene or -N(R1'5'12)-; R1'5'11 is independently C1-C7 alkyl or C3-C14 cycloalkyl: R1-5·1-2 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1'5'3 is independently hydrogen, C1-C7 alkyl, C2-C7 alkenyl, C2-C7alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C5-Cy0aryte or C1-C7 heteroaryl; R1'5'4 is independently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C2-C7 alkenyl, C2-C7alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C6-Cy0aryte, C1-C7 heteroaryl or “amino substituted with one or two R1'5'4'1”; ri5·4'1is independently Ci-C? alkyl or C3-C14 cycloalkyl; R1'3 is independently hydrogen, -CN, -OH or Ci-C7alkyl, C2-C7alkenyl, C2C7alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Ce-Cio aryte or C1-C7 heteroaryl optionally substituted with one, two or three R1 '6'1; R1'54 is independently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C2-C7 alkenyl, C2-C7alkynyl, C3-Ci4cycloalkyl, C3-C14 heterocycloalkyl, C6-Cy0aryte , C1-C7 heteroaryl or amino substituted with one or two R1'6'1'1”; ri6'1·1is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1'7is independently hydrogen, -OR1'7'1, -NR^^R1'7'3o C1-C7 alkyl, C2-C7alkenyl, C2-C7alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C5-C10 aryte or C<-C7heteroaryl optionally substituted with one, two or three R774; R17'1 is independently hydrogen, C1-C7 alkyl, C2-C7alkenyl, C2-C7alkynyl, C3-C14 cycloalkyl, C3-Ci4heterocycloalkyl, C5-C10 aryte or C1-C7 heteroaryl; R1'7-2 and R1-7'3 are independently C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl or C3-C14 cycloalkyl; or, R1'7-2 and R!·7'3 together with the nitrogen atom join together to form a C3-C14 heterocycloalkyl optionally substituted with one, two or three R1-7·2-1; one or more methylenes in the C3-C14 heterocycloalkyl are optionally and independently substituted with an oxygen atom, a sulfur atom, sulfinyl, sulfonyl, carbonyl, vinylidene or -N(R17'2·2)-; R1·7·2·1 is independently Ci-C7alkyl or C3-C14 cycloalkyl; r1-7-2-2is independently C1-C7 alkyl or C3-C14 cycloalkyl; IVIA / t / ZUZZ / U I0400 R17'4eshalogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C2-C7 alkenium, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Ce-Cio arite, C1-C7 heteroaryl or amino substituted with one or two RT7-4- 1».Ri7 Φ1is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1'8is independently halogen, -OH, amino, mercapto, cyano, C1-C7 alkyl, C1C7alkoxy, C1-C7 alkylthio, C2-C7alkenium, C2-C7alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Ce-Cio arite, C1-C7 heteroaryl or amino substituted with one or two R1-®-1”; R1-81 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R2 is -O2'1, cyano, carboxyl or C2-C7alkyl, C3-C14 cycloalkyl or C3-C14 heterocycloalkyl optionally substituted with one, two or three R2“2; R2'1is Ci-C7alkyl, C2-C? alkeniium, C2-C7alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Cs-Ci0aryl or C1-C7 heteroaryl; R22 is independently halogen, hydroxyl, amino, CrC7alkyl, C1-C7 alkoxy, C3Cu cycloalkyl or C3-C14 heterocycloalkyl; In any of the above cases, the heteroatoms in the C3-C14 heterocycloalkyl, C1-C7 heteroaryls are independently selected from one or more of boron, silicon, oxygen, sulfur, setenium, nitrogen and phosphorus; the number of heteroatoms is independently 1,2,3 or 4. IVIA / t / ZUZZ / U I0400 In a certain scheme, some substituents in the pyrazolopyrimidine compound represented by formula I, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof or the prodrug thereof may further have the following definitions, and the definitions of substituents not involved below are those described in any of the above schemes (hereinafter, in a given scheme): When A is C3-C20 cycloalkyl substituted with one or two R1, the C3-C20 cycloalkyl is, for example, C3-C20 monocyclic cycloalkyl, C3-C20 spiro cycloalkyl, C3-C20 fused cycloalkyl or C3-C20 bridged cycloalkyl. C3-C20 monocyclic cycloalkyl is, for example, C3-C6 monocyclic cycloalkyl, for example cyclopropyl, cyclobutyl, cyclopentyl or cyclohexite, for example cyclohexyl. C3-C20 bridged cycloalkyl is, for example, C5-C8 bridged cycloalkyl, for example5- / or In a certain scheme: When A is C3-C20 cycloalkyl substituted with one or two R1, the C3-C20 cycloalkyl is, for example, C3-C20 saturated cycloalkyl. In a certain scheme: ¡ When A is C3C2o cycloalkyl substituted by a R1, the A is for example R1o R In a certain scheme: When R1 is independently C3-C14 heterocycloalkyl, the C3-C14 heterocycloalkyl is, for example, C3-C14 monocyclic heterocycloalkyl, C3-C14 coiled heterocycloalkyl, C3-C14 fused heterocycloalkyl or C3-Cm bridged heterocycloalkyl. C3-C14 monocyclic heterocycloalkyl is, for example, C3-C9 monocyclic heterocycloalkyl having one or two heteroatoms selected from one or two of N, O and S, for example, C3-C5 monocyclic heterocycloalkyl having one or two heteroatoms selected from one or two of N, O and S”, for example, C3-C5 monocyclic heterocycloalkyl that has one or two heteroatoms selected from one or two of N, O and S” and that is connected to a benzene ring by an atom of nitrogen, for example, azetidinyl, morpholinyl, piperidinyl or piperazinyl. Yo Yo Azetidinyl is for example. Morpholinyl is for example u. Piperidinyl is for example either H. Piperazinyl is for example H QQbQ Ln / ZZnZ / 3 / ΥΙΛ In a certain scheme: When R1 is independently C3-C14 heterocycloalkyl, the heteroatom of the C3-C14 heterocycloalkyl cannot be substituted. In a certain scheme: When R1 is independently C3-C14 heterocycloalkyl, the methylene in the C3-C14 heterocycloalkyl cannot be substituted. In a certain scheme: When R1-3 and R1-4 are independently C1-C7 alkyl, the C1-C7 alkyl is, for example, C1-C3 alkyl, for example methyl, ethyl, n-propyl or isopropyl. In a certain scheme: When R1'3'1 is independently C1-C7 alkyl, the C1-C7 alkyl is, for example, C1C3alkyl, for example methyl, ethyl, n-propyl or isopropyl. In a certain scheme: When R1'5 is independently C3-Cu heterocycloalkyl, the C3-Ci4heterocycloalkyl is, for example, C3-C14 monocyclic heterocycloalkyl, C3-C14 spiro heterocycloalkyl, C3-C14 fused heterocycloalkyl or C3-C14 ported heterocycloalkyl. C3-C14 monocyclic heterocycloalkyl is, for example, C3-C9 monocyclic heterocycloalkyl having one or two heteroatoms selected from one or two of N, O and S, for example,"C3-CMonocyclic heterocycloalkyl having one or two heteroatoms selected from one or two of N, O and S, for example, “C3-C5monocyclic heterocycloalkyl having one or two heteroatoms selected from one or two of N, O and S” and which is connected to a benzene ring by a nitrogen atom , for example, azetidinyl. Azetidinyl is for example Λ In a certain scheme: When RiSes independently C3-Cu heterocycloalkyl, the heteroatom of the C3Cu heterocycloalkyl cannot be substituted. In a certain scheme: When R1'5 is independently C3-C14 heterocycloalkyl, the methylene in the C3-C14 heterocycloalkyl cannot be substituted. In a certain scheme: When R151 and R15 2 are independently C1-C7 alkyl, the C1-C7 alkyl is, for example, C1-C3 alkyl, for example methyl, ethyl, n-propyl or isopropyl. In a certain scheme: When Ri 5“1 and R1'5'2 are independently C3-C14 cycloalkyl, the C3-C14 cycloalkyl is, for example, C3-C14 monocyclic cycloalkyl, C3-Cu spiro cycloalkyl, fused C3-C14 cycloalkyl or bridged C3-C14 cycloalkyl. C3-C14 monocyclic cycloalkyl is, for example, C3-C3 monocyclic cycloalkyl, for example cyclopropyl, cyclobutyl, cyclopentyl or cyclohexium, for example cyclobutyl, cyclopenthiium or cyclohexium. ΜΛ / t / ZUZZ / U I0400 C3-C14 bridged cycloalkyl is, for example, Cs-Cg bridged cycloalkyl, e.g. In a certain scheme: When R! s 1 and R152 are independently C3-C14 cycloalkyl, C3-C14 cycloalkyl is, for example, saturated C3-Cucycloalkyl. In a certain scheme: When R15 3 is independently C1-C7 alkyl, the C1-C7 alkyl is, for example, C1C3 alkyl, for example methyl, ethyl, n-propyl or isopropyl. In a certain scheme: When R2 is C2-C7alkyl optionally substituted with one, two or three R2'2, the C2-C7 alkyl is, for example, C2-C4 alkyl, for example ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec -butyl or tert-butyl, for example isopropyl. In a certain scheme: When R2 is C2-C7 alkyl substituted by a R2'2, R2'2 is hydroxyl; the C2-C7 alkyl OH _ WV replaced by an R2 is it for example ¡ In a certain scheme: When R2 is C3-C14 heterocycloalkyl optionally substituted with one, two or three R2'2, the C3-C14 heterocycloalkyl is, for example, C3-C14 monocyclic heterocycloalkyl, C3-C14 spiro heterocycloalkyl, C3-C14 fused heterocycloalkyl or C3-C14 heterocycloalkyl bridged. C3-C14 monocyclic heterocycloalkyl is, for example, C3-C9 monocyclic heterocycloalkyl having one or two heteroatoms selected from one or two of N, O and S, for example, C3-C5 monocyclic heterocycloalkyl having one or two heteroatoms selected from one or two of N, O and S”, for example, “C3-C5 monocyclic heterocycloalkyl having one or two heteroatoms selected from one or two of N, O and S” and which is connected to a benzene ring by one atom of nitrogen, for example, oxetanyl. Morpholinyl oxetanyl is, for example, oxetan-3-yl. In a certain scheme: When R2 is C3-C14 heterocidoalkyl optionally substituted with one, two or three R2'2, the heteroatom of the C3-C14 heterocidoalkyl cannot be substituted except R2'2. In a nutshell: When R2 is C3-C14 heterocidoalkyl optionally substituted with one, two or three R2'2, the methylene in the C3-C14 heterocidoalkyl cannot be substituted. In a certain scheme: When R2 is C3-Ch heterocidoalkyl substituted by a R2-2, R2-2 is halogen or ΊΛ / t / ZUZZ / U I0400 hydroxyl; C3-C14 heterocidoalkyl substituted by a R2*2 is for example OH or F In a certain scheme: The proportion of each isomer in the pyrazolopyrimidine compound represented by formula I may be the same, for example, racemate. In a certain scheme: The atoms of the pyrazolopyrimidine compound represented by formula I, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof or the prodrug thereof may all exist in their natural abundance . In a certain scheme: 4-0 4-0 -i-áv) A is * \< \z0\— / replaced by one or two R1”. In a certain scheme: A is C3-C20 cycloalkyl substituted by an R1. In a certain scheme: A is R1 or R1. In a certain scheme: R1 is independently halogen, -CN, -NR1'3RM, -C (= O) R1-5, -C (= NR1-6) R1'7o O-Ch cycloalkyl, C3-C14 heterocidoalkyl, C6-Cw arite or C1- C7 heteroaryl optionally substituted with one, two or three R1'8; R1-3and ri-4 are independently hydrogen, -S (= O)zR1'3'1, -C (= O) R1'3'2, -C (= NR1' 3-3)NR1 -3-sRi-3-6 _sο^ΝΗ1-3·^-3·3, _cQjNRi3-9Ri-3-wQd-Cz alkyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Ce-Cw ariio or C1-C7 heteroaryl” optionally substituted with one, two or three R1-3·'1; RI-3-! and R1-3-2 is independently alkyl, C3-C14 or Cl03 lq U í IO, C3-C14 heterocycloalkyl or Cg-Cw aryl” optionally substituted with one or two R1'3·1·1”; Ri-3-1-1 is independently C1-C7 alkyl; R1'3'3is independently hydrogen; R^~3 3, ri-3-s, ri-3-7, Ri-3-8, R1-3-9 and Ri-3-ions are independently C1-C7 alkyl or C3-C14 cycloalkyl; R1'3'1is independently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, Ci-C-¿ alkoxy, C1-C7 alkylthio, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Cs-Ci0 aryl, C1- C7 heteroaryl or amino substituted with one or two ri·3·'^; ri-3-11-1 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1'5 is independently hydrogen, -NR1'5·^1·5·2, -O1·5·3o C1-C7 alkyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C6-Cy0aryl or C1-C7 heteroaryl optionally substituted with one, two or three R1'5'4; R15· and R-5-2are independently hydrogen, C1-C7 alkyl or C3-C14 cycloalkyl; R1'5'3 is independently hydrogen, C1-C7 alkyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C6-Ci0aryl or C1-C7 heteroaryl; R1'5'4is independently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Ce-Cio aryl, C1-C7 heteroaryl or amino substituted with one or two R15-4-1; ri-s-4-ιesindependently C1-C7 alkyl or C3-C14 cycloalkyl; R1's independently hydrogen, -CN, -OH; R1'7is independently hydrogen, -NR^R1·7·3; R1·72and ri-7-3 are independently C1-C7 alkyl or C3-C14 cycloalkyl; or, R1-7'2 and R1'7'3 together with the nitrogen atom join to form a C3-C14 heterocycloalkyl optionally substituted with one, two or three Ri-7-2-1. one or more methylenes at the C3-C14 heterocycloalkyl are optionally and independently substituted with an oxygen atom, a sulfur atom; R1'7'2'1 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1'3is independently halogen, -OH, amino, mercapto, cyano, C1-C7 alkyl, C1C7 alkoxy, C1-C7 alkylthio, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Cg-Cio aryl, C1-C7 heteroaryl or substituted amino with one or two r1-®-1; r1-®-1 is independently C1-C7 alkyl or C3-C14 cycloalkyl. In a certain scheme: R1is independently cyano, halogen, -NRV3R1'4, -C (= O) R1Λ -C (= NR^6) R1'7, IVIA / t / ZUZZ / U 10400 C1-C7 heteroaryium or C3-C14 heterocycloalkyl. In a certain scheme: R1 is independent -NR1'3R1'4, -C (= O) R1'5o C3-C14 heterocycloalkyl. In a certain scheme: R1-3 and ri-4 are independently hydrogen, -S(-O)2R1'3'1o C1-C7 alkyl; R1'3'1 is independently C1-C7 alkyl. In a certain scheme: R1'5is independent -NR1'5'1R1'5'2, -O1-5'3o C3-C14 heterocycloalkyl; R1-5'1 and R1-5'2 are independently hydrogen, C1-C7 alkyl or C3-C14 cycloalkyl; Is R1'5'3 independently hydrogen or CrC? I rent. In a certain scheme: Independent R1Ses -NR1·5'·^1·5·2, -O1'5'3o C3-C14 heterocycloalkyl; R1'5'1 and R15'2 are independently hydrogen, C1-C7 alkyl or C3-Ci4cycloalkyl; R1-5'3is hydrogen. In a certain scheme: R2 is C2-C7 alkyl, C3-Ci4cycloalkyl or C3-C14 heterocycloalkyl optionally substituted with one, two or three R2'2; R2'2is independently halogen or hydroxyl. In a certain scheme: R2 is C2-C7 alkyl or C3-Ci4heterocycloalkyl substituted by a R2'2”; R2'2is halogen or hydroxyl. IVIA / t / ZUZZ / U I0400 In a certain scheme: R2 is C2-C7 alkyl or C3-C14 heterocycloalkyl substituted by a R2'2”; R2'2is hydroxyl. In a certain scheme: R1 is independently halogen, -CN, -N^R1'4, -C (= O) R15, -C (= NR16) R17 or C3-Cu cycloalkyl, C3-Cu heterocycloalkyl, C5-Cw aryl or optionally substituted C1-C7 heteroarylium with one, two or three R18; R1'3and R1'4are independently hydrogen, -S (= O)2R1·3'1, -C (= O) R1'3'2, -C (= NR13-3) NR1 -3-5Ri-3-6 _so^NR^R1-3-8, -C (= O) NR^^R1'3'10o Ci-c7alkyl, C3-C14 cycloalkyl, C3-Ci4heterocycloalkyl, Ce-C™ aryl or C1-C7 heteroarylium optionally substituted with one, two or three R1'3·11; ri-3-i and Ri-3-2sor (independently C1-C7 alkyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl or Cs-Cw aryl” optionally substituted with one or two Ri-3-i-i;Ri-3-1- 1isindependently C1-C7 alkyl; R1·3'3is independently hydrogen; R1'3'5, R1'3'6, R1'3'7, R1'3'3, R1-3'9 and r-3-13 are independently C1-C7 alkyl or C3-C14 cycloalkyl; R1'3'11 is independently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Cs-Cw aryl, C1-C7 heteroaryl or amino substituted with one or two Ri-3-u-i· ^1-3-11-1esindependently C1-C7 θ alkyl or C3-C14 cycloalkyl; R1'5is independently hydrogen, -IMR^R1'5'2, -O1'5'3o “C1-C7 alkyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Cs-Cw aryl or C1-C7 heteroaryl optionally substituted with one , two or three R1'5“j R-i-5-ι and R1-5-2 are independently hydrogen, C1-C7 alkyl or C3-C14 cycloalkyl; R1·5·3is independently hydrogen, C1-C7 alkyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Cs-Cw aryl or C1-C7 heteroaryl; R1-5-4is independently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, Ci-C? alkoxy, C1-C7 alkylthio, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Cs-Cw aryl, C1-C7 heteroaryl or amino substituted with one or two R15-4-1”; R1-5-4-1 is independently C1-C7® alkyl or C3-C14 cycloalkyl; R1·® is independently hydrogen, -CN, -OH; R1'7is independently hydrogen, -NR17'2R1·7'3; ri-7-2 and R! 7 3 are independently C1-C7 alkyl or C3-C14 cycloalkyl; or, R1'7'2 and R1-7'3 together with the nitrogen atom join to form a C3-C14;5heterocycloalkyl optionally substituted with one, two or three Ri-7-2-1;One or more methylenes at C3 -C14 heterocycloalkyl are optionally and independently substituted with one oxygen atom, one sulfur atom; R1-7-2-1 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1'3is independently halogen, -OH, amino, mercapto, cyano, C1-C7 alkyl, C1C7alkoxy, C1-C7 alkylthio, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Cs-Cw aryl, C1-C710heteroaryl or amino substituted with one or two R1-3-1”; R1-®-1 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R2 is C2-C7 alkyl, C3-C14 cycloalkyl or C3-C14 heterocycloalkyl” optionally substituted with one, two or three R2-2; R2'2 is independently halogen or hydroxyl; 15In any of the above cases, the heteroatoms in the C3-C14 heterocycloalkyl, C1-C7 heteroaryls are independently selected from one or more of boron, silicon, oxygen, ΊΛ / t / ZUZZ / U I0400 sulfur, selenium, nitrogen and phosphorus; the number of heteroatoms is independently 1,2,3 or 4. In a certain scheme: A is C3-C20 cycloalkyl substituted with one or two R1; R1 is independently cyano, halogen, -NR^R1'4, -C (= O) R15, -C (- NR1'6) R1'7, C1-C7 heteroanyl or C3-C14 heterocycloalkyl; R1'3 and Ri-4 are independently hydrogen, -S (= O^R1'3'1o C1-C7 alkyl; R73'1 is independently C1-C7 alkyl; R1·5is independent -NR1·5'^1·5·2, -O15·3o C3-C14 heterocycloalkyl; R1-5-1and R1-5'2are independently hydrogen, CrC? alkyl or C3-C14 cycloalkyl; Is R1-5'3 independently hydrogen or CrC? I rent; R2 is C2-C7 alkyl or C3-C14 heterocycloalkyl substituted by a R2 2"; R2 2is halogen or hydroxyl. In a certain scheme: A is C3-C20 cycloalkyl substituted by an R1; R1 is -NR1'3R1'4, -C (= O) R1-5o C3-C14 heterocycloalkyl; R1'3 and Ri-4 are independently hydrogen, -S (= O)2R13'! or C1-C7 alkyl; Rb3“!is independently C1-C7 alkyl; R1'5is -NR1·5-^1·5'2, -O1-5'3o C3-C14 heterocycloalkyl; R·'5'1 and R1-5'2 are independently hydrogen, C1-C7 alkyl or C3-C14 cycloalkyl; R1'5'3 is hydrogen or C1-C7 alkyl; R2 is C2-C7 alkyl or C3-C14 heterocydokyl substituted by a R2~2; R2'2is hydroxyl. In a certain scheme: A is C3-C20 cycloalkyl substituted by an R1; R1 is -NR1'3R1'4, -C (= O) R1'5o C3-C14 heterocycloalkyl; R13 and R14 are independently hydrogen, -S (= ObR1'31o C1-C7 alkyl; R1'3'1 is independently C1-C7 alkyl; R1'5is -NR^R1·5'2, -O1'5'3o C3-C14 heterocycloalkyl; R151 and R1'5'2 are independently hydrogen, C1-C7 alkyl or C3-C14 cycloalkyl; R1'5'3 is hydrogen; R2 is C2-C7 alkyl or C3-C14 heterocycloalkyl substituted by a R2'2”: R2'2 is hydroxyl. In a certain scheme: Yo JWV | or <> A is R1 or R1; R1is -NR^R1·4, -C (= O) R1So C3-C14 heterocycloalkyl; Ri-3 and Ri-4 are jncjepenc{ien|emenphehydrogen, -S (= O)2R1'3'io C1-C7 alkyl; R1'3'1 is independently C1-C7 alkyl; R1'5is -O1'5'3o C3-C14 heterocycloalkyl; R1'5'1 and RV5'2 are independently hydrogen, C1-C7 alkyl or C3-C14 cycloalkyl; R1'5'3 is hydrogen or C1-C7 alkyl; R2 is C2-C7 alkyl or C3-C14 heterocycloalkyl substituted by a R2'2”; R2'2is hydroxyl. In a certain scheme: Yo A is R1 or R1; ΊΛ / t / ZUZZ / U I0400 R1 is -NR1'3R1í -C (= O) R1-5o C3-C14 heterocycloalkyl; R1'3and ri-4 are independently hydrogen, -S (= O^R1'3'1o C1-C7 alkyl; R1'3'1is independently C1-C7 alkyl; R1'5is -NR1'5'1R1·5'2, -O1-5'3o C3-C14 heterocycloalkyl; R1'5'1 and R1-5-2 are independently hydrogen, C1-C7 alkyl or C3-Cu cycloalkyl; R1-5'3 is hydrogen or C1-C7 alkyl; R2es 4W.Í I OH In certain scheme, in the pyrazolopyrimidine compound represented by formula II, the pharmaceutically acceptable salt thereof, the soivate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metaboiite thereof or the prodrug thereof, the compound pyrazolopyrimidine represented by formula II is any of the following compounds: ΜΛ / t / ZUZZ / U I0400 QQfrQ Ln / ZZnZ / q / ΥΙΛ In certain scheme, in the pyrazoiopyrimidine compound represented by formula II, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof or the prodrug thereof, the pyrazoiopyrimidine compound represented by formula II is any of the following compounds: OR EITHER U™, su1H NMR(400 MHz, MeOD) is δ 8.85 (s, 1 H), 8.00 (t, J = 7.9 Hz, 1 H), 7.80 (d, J = 8.1 Hz, 1 H), 7.68 (d, J = 7.7 Hz, 1 H), 7.62 (d, J = 8.6 Hz. 2 H), 7.28 (d, J = 8.6 Hz, 2 H), 5.78 - 5.68 (m, 1 H), 5.06 (d, J = 10.3 Hz, 1 H), 4.95 (s, 1 H), 4.82 (s, 2 H), 3.82 - 3.76 (m, 25 H), 2.81 (s, 1 H), 2.71 (s, 3 H), 2.49 (s, 1 H), 2.08 (d, J = 10.9 Hz, 3 H), 1.94 (d, J = 15.0 Hz , 3 H), 1.72 (s, 4 Η), 1.59 (d, J = 7.0 Hz, 6 H); rzzz Jx J-N Gj; Γ ~ OHOZO^ « ,SLi Ή NMR (400 MHz,CDCyes 6 8 87 (dJ = 2.1 Hz, 1 H), 7.91 (td, J = 7.9, 1.5 Hz, 1 H), 7.78 (d, J = 8.0 Hz, 1 H), 7.54 (t, J = 7.9 Hz, 2 H), 7.39 (d, J = 7.7 Hz, 1 H), 7.21 (d, J = 8.5 Hz, 2 H), 5.72 (ddt, J= 16.4, 10.2, 6.2 Hz, 1 H), 5.07 (dd, J- 10.2, 1.1 Hz, 1 H), 35 4.96 (dd,J- 17 ,1, 1.2 Hz, 1 H), 4.77 (d, J = 6.2 Hz, 2H), 4.25 - 4.10 (m, 2H), 3.95 (s, 1H),2.73 (s, 1H), 2.56 (dt , J = 15.5, 10.8 Hz, 1 H), 2.28 (el, J = 7.9 Hz, 1 H), 2.14 (d, 10.6 Hz, 1 H), 2.05 - 1.97 (m, 1 Η), 1.78 (dd, J = 19.0, 8.5 Hz, 1 H), 1.67 (dt, J = 10.1,6.1 Hz, 3 H), 1.61 (s, 6 H), 1.59- 1.44 (m, 1 H), 1.34 - 1.26 (m, 3 H); ^4 / HN N * Ó CU γ oh oXh15, su1H NMR(400 MHz, MeOD) is δ 8.84 (d, 7= 1.4 Hz, 1 H), 8.00 (Id, J = 7.9, 4.0 Hz, 1 H), 7.83 - 7.76 ( m, 1H), 7.67 (dd, J = 7.7, 0.7 Hz, 1H), 7.60 (dd, J = 8.4, 5.7 Hz, 2H), 7.19 (dd, 7 = 13.2, 8.6 Hz, 2H) , 5.73 (ddd, 7= 17.0, 6,1,4.1 Hz, 1 H), 5.08-5.03 (m, 1 H), 4.95 (day, 7 = 1.3 Hz, 1 H), 4.86 - 4.79 (m, 2 H), 2.72 (s, 1 H), 2.58 (s, 1 H), 2.27 (d, 7 = 6.7 Hz, 1 H), 2.13 (d, = 10.0 Hz, 1H), 1.96 (d, 7 = 10.2 Hz, 1H), 1.80 - 1.66 (m, 4H), 1.64- 1.52 (m, 7H); , su1H NMR (400 MHz, CDCh) is δ 8.86 (d, 7 = 4.2 Hz, 1 H), 7.97 - 7.88 (m, 1 H), 7.79 (d, 7= 8.0 Hz, 1 H), 7 .53 (dd, 7 = 12.3, 8.5 Hz, 2H), 7.39 (d, 7=7.6 Hz, 1 H), 7.28 - 7.15 (m, 2 H), 5.80- 5.65 ( m, 1 H), 5.06 (d, J= 10.0 Hz, 1 H), 4.95 (d, 7 = 17.1 Hz, 1 H), 4.77 (d, 7 = 6.0 Hz, 2H), 3.10 ( d, 7 = 12.1 Hz, 3 H), 2.98 (s, 3 H), 2.67 - 2.57 (m, 1 H), 2.14 (dd, J = 20.9, 10.3 Hz, 1 H), 2.06 - 1.97 (m, 2 H), 1.92 (d, 7 = 14.0 Hz, 1 Η), 1.78 - 1.66 (m, 4 H), 1.61 (s, 6H), 1.49 (dd, 7 = 22.8, 12.2 Hz, 1 H); EITHER , its'HRMN (400 MHz, CDCb) is δ 8.85 (d,7=4.7Hz, 1 H), 7.91 (dt, 7 = 10.7, 7.9 Hz, 1 H), 7.78 (d, 7 = 7.8 Hz, 1 H), 7.53 (dd, 7 = 12.0, 8.5 Hz, 2H), 7.39 (dd, 7 = 7.6, 2.4 Hz, 1 H), 7.22 (dd,J=19.5, 8.5 Hz, 2H), 5.71 (ddt, 7=16.4, 10.2,6.2 Hz, 1 H), 5.06 (d, 7 = 10.2 Hz, 1 H), 4.95 (d, 7= 17.1 Hz, 1 H), 4.77 (d, 7 = 6.1 Hz, 2 H), 4.21 (dd, 7= 16.4 , 8.6 Hz, 2H), 4.10 - 4.02 (m, 2H), 2.63 - 2.52 (m, 2H), 2.35 - 2.20 (m, 2H), 2.15 - 2.07 (m, 1H), 2.00 (dd, 7 = 13.4 , 3.0 Hz, 2 H), 1.92 - 1.83 (m, 1 H), 1.79 - 1.63 (m, 4 H), 1.60 (s, 6 H), 1.48 (ddd, 7 = 24.7, 12.5,2.5Hz, 1H); , its Ή NMR (400 MHz, CDC!3) is δ 8.86 (s, 1 H), 7.93 - 7.85 (m, 1 H), QQfrQ Ln / ZZnZ / 3 / ΥΙΛ 7.78 (d, J = 7.8 Hz, 1 H), 7.52 (d, J = 8.5 Hz, 2 H), 7.39 (dd, J = 7.6, 0.7 Hz, 1 H), 7.19 (d, J = 8.5 Hz, 2 H), 5.71 (ddt, J = 16.4, 10.2, 6.2 Hz, 1 H), 5.05 (dd, J- 10.2, 1.1 Hz, 1 H), 4.94 (dd, J = 17.1, 1.3 Hz, 1 H), 4.77 (d, J = 6.2 Hz, 2 H), 4.11 (d, J=8.9 Hz, 1 H), 3.24 (t, 7.0Hz, 4H), 2.52-2.43 (m, 1H), 2.14-2.00 (m, 3H), 1.92 (d, J = 11.2 Hz, 4H), 1.60 (s,6H), 1, 45 (dt, J = 14.9, 7.5 Hz, 2 H), 1.23- 1.08 (m, 2 H); either , su1H NMR (400 MHz, CDCI3) is δ 8.84 (d, J = 3.7 Hz, 1 H), 7.94 (dd, J = 14.8, 6.9 Hz, 1 H), 7.76 (d, J = 7.9 Hz, 1 H), 7.58 - 7.50 (m, 2 H), 7.42 (dd, J = 7.5, 4.1 Hz , 1H), 7.22 (dd, J = 15.8, 8.5 Hz, 2H), 5.71 (dd, J = 11.5, 5.4 Hz, 2H), 5.07 (d, J = 10.2 Hz, 1H), 4.95 (d, J = 17.1 Hz, 1 H), 4.77 (d, J = 6.1 Hz, 2 H), 2.82 - 2.72 (m, 1 H), 2.60 (s, 1 H), 2.12 2.01 (m, 3H ) ,1.92 (d, J = 12.5 Hz, 1 H), 1.81 -1.67 (m,3H), 1.62 (s, 6 H), 1.54- 1.43 (m, 1 H), 0.93 - 0.78 (m, 3H), 0.52 (s, 2H); or _U__ Λ / J Laza J OH p -9 Ά0, SU1H NMR (400 MHz, CDCh) is δ 8.88 (s, 1 H), 7.91 (t, J = 7.9 Hz, 1 H), 7.77 (d, J = 7.9 Hz, 1 H), 7.56 ( d, J = 8.5 Hz, 2 H), 7.40 (d, J = 7.4 Hz, 1 H), 7.19 (d, J = 8.5 Hz, 2 H), 5.78-5.66 (m, 1 H), 5.07 (dd, J = 10.2, 1.0 Hz, 1 H), 4.96 (dd, J = 17.1, 1.2 Hz, 1 H), 4.77 (d, J = 6.2 Hz, 2 H), 4.42 (d, J = 7.6 Hz, 1 H), 3.49 - 3.35 (m, 1 H), 3.04 (s, 3 H), 2.57 - 2.46 (m, 1H), 2.29 - 2.17 (m, 2H), 2.05 - 1.96 (m, 8H), 1.56-1.65 (m, 2H), 1.41-1.50 (m, 2H) ); ΗΝ ^ΝΗ , su1Η NMR (400 ΜΗζ, MeOD) is δ 8.84 (s, 1 Η), 8.02 (m, 1 Η), 7.80 (m, Η), 7.72-7.58 (m, 3 Η), 7.25 (m, 2 Η), 5.73 (ddt, J = 16.5, 10.3, 6.1 Ηζ, 1 Η), 5.05 (dd, J = 10.2, 1.0 Ηζ, 1 Η), 4.95 (d, 1 Η), 4.83 (d, J = 6.1 Ηζ, 2 Η), 3.54-3.42 (m, 1 Η), 2.59 (m, 1Η), 2.14 (m, Η), 1.98 (m, 2 Η), 1.83 (m, 1 Η), 1.68 (m, 2 Η), 1.60 (s, 6 Η), 1.50 (m , 2H); , su1Η NMR (400 ΜΗζ, DMSO) is δ 10.28 (s, 1 Η), 8.88 (d, J = 1.8 Ηζ, 1 Η), 8.09 - 7.97 (m, 1 Η), 7.75 (d, J = 8.4 Ηζ, 1 Η), 7.66 (dd, J = 20.6, 8.5 Ηζ, 3 Η), 7.19 (dd , J = 11.1, 8.7 Ηζ, 2 Η), 5.74 - 5.61 (m, 1 Η), 5.00 (d, J - 10.2 Ηζ, 1 Η), 4.82 (re, J - 17.1 Ηζ, 1 Η), 4.69 (re, J = 5.5 Ηζ, 2 Η), 3.23 (s, 1 Η). 2.74 (t, J - 12.1 Ηζ, 1 Η), 2.53 (s, 1 Η), 2.12 (re, J - 10.1 Ηζ, 1 Η), 1.98 (re, J - 13, 2 Ηζ, 1 Η), 1.82 (re, J = 13.2 Ηζ, 2 Η), 1.77-1.57 (m, 3 Η), 1.49 (re, J = 18.2 Ηζ, 6 H) ; Μ!, su1Η NMR (400 ΜΗζ, DMSO) is δ 10.27 (s, 1 Η), 8.89 (s, 1 Η), 8.12 (s, 1 Η), 7.74 (dd, J = 22.6, 8 ,3 Ηζ, 3 Η), 7.64 (d, J = 7.3 Ηζ, 1Η), 7.37 (d, J = 8.5 Ηζ, 2Η), 5.76-5.61 (m, 1Η), 5.34 (s, 1Η), 5.01 ( dd, J = 10.3, 1.2Hz, 1H), 4.84 (d, J = 17.1 Hz, 1 H), 4.70 (d, J = 5.7 Hz, 2 H), 3.62 (s, 1 H), 3, 12 (s, 1 H), 2.71-2.58 (m, 8 H), 2.38 (d, J = 9.2 Hz, 2 H), 30 1.47 (s, 6 H), 1, 32-1.24 (m, 1H); , its Ή NMR (400 MHz, DMSO) is δ 10.26 (s, 1 H), 8.88 (s, 1 H), 8.07 (t, J = 7.8 Hz, 1 H), 7.76 (d, J = 8.0 Hz, 1 H), 7.65 ( dd, J = 14.5, 7.9 Hz, 2 H), 7.22 (d, J = 8.5 Hz, 2 H), 5.74 - 5.60 (m, 1 H), 5, 35 (s, 1 H), 5.00 (d, J = 10.3 Hz, 1 H), 4.83 (d, J = 17.1 Hz, 1 H), 4.69 (d, J = 5.6 Hz, 2 H) , 3.74 (s, 3 H), 3.24 - 3.15 (m, 1 H), 2.77 (t, J = 12.0 Hz, 1 H), 2.37 (d, J = 14.0 Hz, 1 H) , 2.25 (td, J = 13.4, 4.6 Hz, 1 H), 1.99- 1.84 (m, 3 H), 1.67- 1.50 (m, 2 H), 1.49 í d, J = 14.0 Hz , 6H); A. , its NMR(400 MHz, MeOD) is δ 8.86 (s, 0 H), 8.11-8.01 (m, 1 H), 7.94 (d, J = 7.9 Hz, 2H), 7.67 (d, J = 7.6 Hz, 2H), 7.62 (d, J = 8.6 Hz, 2H), 7.28 (d, J - 8.5 Hz, 2H), 5.83-5.74 (m, 1H), 5.09 (dd, J = 7.9, 4.4 Hz, 3H), 4.98 (dd, J = 17.1, 1.3 Hz, 2H), 4.85 (d, J = 6.7 Hz, 2H), 2.87 (s, 1 H), 2.64 (s, 1 H), 2.47 (s, 3 H), 1.97 - 1.67 (m, 8 H); «xiK Ó d-J OH zM-i-34 Ó, its Ή NMR(400 MHz, MeOD) is δ 8.87 (d, J = 6.6 Hz, 1 H), 8.06 (t, J = 7.9 Hz, 1 H), 7.95 (d, J = 7.9 Hz, 1 H), 7.68 (dd, J = 7.8, 5.4 Hz, 2 H), 7.61 (d, J = 8.6 Hz, 1 H), 7.41 (d, J = 8.4 Hz, 1 H), 7.24 (t, J = 8.7 Hz, 1 H), 5.84 - 5.72 (m, 1 H), 5.09 (d, J = 6, 2 Hz, 2 H), 5.07 (d, J = 1.3 Hz, 1 H), 5.02 - 4.94 (m, 2 H), 4.90 (s, 2 H), 4.84 (d, J = 6.7 Hz, 2 H), 3.15 (d, J = 2.6 Hz, 1 H), 3.08 (s, 1 H), 2.95 (s, 1 H), 2.71 (s, 1 H), 2.43 (s, 1 H ), 1.93-2.03 (ni, 3 H), 1.76 (s, 2 H), 1.51 (s, 1 H), 1.31 (d, J = 4.3 Hz, 3 H), 0.89 (dd , J = 20,1,9.0 Hz, 4H); p H.N. I-35 VJ, its Ή NMR (400 MHz, CDCI3) is δ 8.87-8.79 (m, 1H), 8.14-8.07 (m, 1H), 8.04-7.96 (m, 1H), 7.89-7.80 (m, 1H), 7.61-7.50 (m, 2H), 7.38-7.32 ( m, 1H), 7.25 - 7.19 (m, 1H), 7.01 ( t, J = 3.4 Hz, 1H), 5.72 (ddd, J = 16.6, 11.1,8.6 Hz, 1H), 5.17 - 5.09 (m, 2H), 5.04 4.98 (m, 1H), 4.98 - 4.92 (m, 1H) ), 4.87 - 4.77 (m, 2H), 4.73 - 4.64 (m, 2H), 4.20 - 4.06 (m, 1H), 3.47 - 3.38 (m, 1H), 3.38 - 3.29 (m, 1H), 3.05-2.98 (m, 1H\ 2.49-2.35 (m, 2H), 2.27-2.17 (m, 1H), 2.07-1.86 (m, 4H), 1.75-1.60 (m, 3H); A QQfrQ Ln / ZZnZ / q / ΥΙΛ , its NMR (400 MHz, CDCh) is δ 8.77 (s, 1H), 8.16-8.07 (m, 1H), 8.03 (d, J = 7.6 Hz, 1H), 7.83-7.75 (m, 1H), 7.56 (dd, J = 12.6,6.1 Hz, 2H), 7.33 (d, J = 8.5 Hz, 1H), 7.21 (d, J = 8.5 Hz, 1H), 5.72 (dd, J = 17.0, 10.3 Hz, 1H), 5.13 (dd, J = 9.1,6.1 Hz, 2H), 4.96 (d, J = 17.0 Hz, 2H), 4.81 (d, J = 7.2 Hz, 2H), 4.69 (d, J = 6.2 Hz, 2H), 4.41 - 4.28 (m, 2H), 3.86 (s, 1 H), 3.77 (t, J = 6.6 Hz, 1 H), 3.63-3.50 (m, 2 H), 2.98 (m, 1 H), 2.15 (m, 1 H), 1.97 (dd, J = 18.9, 9.6 Hz, 2H), 1.78 (d, J = 5.0 Hz, 2H), 1.65 (d, J = 8.7Hz, 2H); , its Ή NMR (400 MHz, CDCh) is δ 8.69 (s, 1 H), 8.18 (d, J = 8.0 Hz, 1 H), 8.10 (dd, J = 17.9, 7.6 Hz, 1 H), 7.81- 7.72 (m, 1 H), 7.63-7.49 (m, 2 H)), 7.25 (d, J = 8.4 Hz, 1 H), 7.19 (d, J = 8.3 Hz, 1 H), 5.70 (d, J = 6.8 Hz. 1 H), 5.15 (d, J = 10, 1 Hz, 1 H), 5.14 - 5.07 (m, 1H), 4.95 (d, J = 16.6 Hz, 1H), 4.83 (t, J = 6.7 Hz, 2H), 4.71 (s, 2H), 2.54 (dd , J = 24.9, 12.6 Hz, 2H), 2.30 (d, J = 11.2 Hz, 1H), 2.18 (d, J = 13.5 Hz, 1H), 2.02 (d, J = 12.9 Hz, 1H), 1.961.80 (m, 2H), 1.78 (d, J = 16.1 Hz, 1 H), 1.49 (dd, J - 26.4, 11.2 Hz, 2 H); , su1H NMR (400 MHz, methanoi-D4) is δ 8.85 (d, J = 1.1 Hz, 1 H), 8.05 (id, J = 7.9, 4.8 Hz, 1 H), 7.96 - 7.86 (m, 1 H), 7.67 (d, J = 7.6 Hz, 1H), 7.59 (ddd, J = 9.2, 4.6, 2.3 Hz, 2H), 7.25-7.19 (m, 1H), 7.19 - 7.11 (m, 1H ), 5.78 (ddt, J = 16.5, 10,1,6.1 Hz, 1 H),5.12 - 5.07 (m, 2 H), 5.06 (t, J - 1.3 Hz, 1 H), 4.98 (dd, J - 17.0, 1.4 Hz, 1 H), 4.90 (d, J = 1.4 Hz, 2 H), 4.25-4.19 (m, 1H), 4.14 (dd, 14.1.7.1 Hz, 1H), 2.34 - 2.12 (m, 2H), 2.07 (dd, J = 17.0, 4.1 Hz, 1H), 1.99- 1.82 (m, 1H), 1.74- 1.65 (m, 2H), 1.65- 1.53 (m, 2H), 1.31 (d, 4.2 Hz, 3 H), 1.29- 1.25 (m,2H); έοοΗ , su1Η NMR (400 ΜΗζ, methanol-dD is δ 8.84 (s, 1 Η), 8.05 (t, J = 7.9 Ηζ, 1 Η), 7.92 (d, J = 8.1 Ηζ, 1 Η), 7.66 (dd, J = 7.6, 0.9 Ηζ, 1 Η), 7.63 - 7.53 ( m, 2Η), 7.22 7.14 ( m, 2Η), 5.84 - 5.74 (m, 1H), 5.10 - 5.07 (m, 2H), 5.06 (q, J = 1.3 Ηζ, 1H), 4.98 (dq, J = 17.0, 1.4 Hz, 1 H ), 4.89 (dt, J = 6.1, 1.4 Hz, 2 H), 2.71 (d, J = 6.9 Hz, 1 H), 2.59 (s, 1 H), 2.24 (dd, J = 16.4, 7.8 Hz, 2 H), 2.04 (d, J = 8.5 Hz, 1 Η), 1.73 (td, J = 10.9, 6.8 Hz, 6 H). In a certain scheme, in the pyrazolopyrimidine compound represented by formula I, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof or the prodrug thereof, the pyrazolopyrimidine compound represented by formula II is any of the following compounds: In a certain scheme, in the pyrazolopyrimidine compound represented by the formula IL the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof or the prodrug thereof, the compound of Pyrazolopyrimidine represented by formula II is any of the following compounds: QQfrQ Ln / ZZnZ / q / ΥΙΛ QQfrQ Ln / ZZnZ / 3 / ΥΙΛ (i-1-1), su1H NMR(400 MHz, MeOD) is δ 8.85 (s, 1 H), 8.46 (s, 2 H), 7.99 (t, J = 7.9 Hz, 1 H), 7.79 (d, J = 8.0 Hz, 1 H), 7.65 (dd, J = 16.6, 8.1 Hz, 3H), 7.22 (d, J = 8.6 Hz, 2 H) , 5.73 (ddt, J = 16.3, 10.2, 6.1 Hz, 1 H), 5.05 (dd, J = 10.3, 1.1 Hz, 1 H), 4.93 (dd, J = 17.1, 1.3 Hz. 1 H), 4.82 (d, J = 6.1 Hz. 2 H), 2.90 (s, 6 H), 2.60 (d, J = 8.4 Hz, 1 H), 2.21 (s, 2 H), 2.10 (d, J = 10.6 Hz, 2H), 1.70 (d, J = 11.4 Hz, 4 H), 1.59 (s, 6 H); (1-1-2), its 'H NMR (400 MHz, CDCh) is δ 8.86 (s, 1 H), 8.54 (s, 1 H), 7.95 (t, J = 7.9 Hz, 1 H) , 7.75 (d, J = 8.0 Hz, 1 H), 7.59 (d, J = 8.5 Hz, 2H), 7.43 (d, J= 7.6 Hz, 1 H), 7.32 (d , J = 8.5 Hz, 2 H), 5.72 (ddt. J = 16.5, 10.3, 6.2 Hz, 1 H). 5.06 (d, J = 10.2 Hz, 1 H), 4.95 (dd, J = 17.1, 1.0 Hz, 1 H), 4.75 (d, J = 6.1 Hz, 2 H), 3.05 (m , 1 H), 2.93 (m, 1 H), 2.68 (s, 6 H), 2.32 (m, 2 H), 1.84 (m, 6 H), 1.60 (s, 6 H); VJ (I-3-1), its ’H NMR (400 MHz, CDCh) is δ 8.87 (s, 1H), 7.90 (t, J = 7.9 Hz, 1H), 7.78 (d, J = 8.0 Hz, 1H), 7.53 (d, J = 8.5 Hz, 2H), 7.39 (dd, J = 7.6, 0.5 Hz, 1 H), 7.20 ( d, J = 8.5 Hz, 2 H), 5.72 (ddt, J = 16.4, 10.2, 6.2 Hz, 1 H), 5.06 (dd, J = 10.2, 1.0 Hz, 1 H), 4.95 (dd , J = 17.1. 1.2 Hz, 1 H), 4.76 (d, J = 6.2 Hz, 2 H), 4.04 (s, 1 H), 2.66 (m, 4 H), 2.58 - 2.47 (m, 1 H), 2.16 (ΠΊ, 4 H), 1.96 (m, 2 H), 1.87- 1.78 (m, 4 H), 1.60 (s, 6 H), 1.58 - 1.39 (m, 4 H); (I-3-2), its ’H NMR (400 MHz, CDCh) is δ 8.87 (s, 1H), 7.92 (t, J = 7.9 Ηζ, 1 Η), 7.80 (d, J = 8.0 Ηζ, 1 Η), 7.52 (d, J = 8.5 Ηζ, 2Η), 7.38 (d, J = 7.6 Hz, 1 H), 7.29 (t, J = 4.2 Hz, 2 H), 5.79 - 5.66 (m, 1 H), 5.06 (dd, J = 10.2, 1.0 Hz, 1 H), 4.96 (dd, J = 17.1, 1.2 Hz, 1 H), 4.77 (d, J = 6.2 Hz, 2 H), 4.02 (s, 1 H), 2.70 - 2.50 (m, 5 H), 2.26 (s, 1 H), 1.98 ( m, 4 H), 1.82 (s,4H), 1.69- 1.56 (m, 10 H); either Ñ V (1-8-1), its Ή NMR (400 MHz, CDCb) is δ 8.86 (s, 1 H), 7.93 - 7.85 (m, H), 7.78 (d, J = 7.8 Hz, 1 H), 7.52 (d, J = 8.5 Hz, 2 H), 7.39 (dd, J = 7.6, 0.7 Hz, 1 H), 7.19 (d, J = 8.5 Hz, 2 H), 5.71 (ddt, J = 16.4, 10.2, 6.2 Hz, 1 H), 5.05 (dd, J = 10.2, 1.1 Hz, 1 H), 4.94 (dd , J = 17.1, 1.3 Hz, 1 H), 4.77 (d, J = 6.2 Hz, 2 H), 4.11 (re, J = 8.9 Hz, 1 H ), 3.24 (t, J = 7.0 Hz, 4 H), 2.52 - 2.43 (m, 1 H), 2.14 - 2.00 (m, 3 Η), 1.92 (d, J = 11 ,2 Hz, 4 H), 1.60 (s, 6 H), 1.45 (dt, J = 14.9, 7.5 Hz, 2 H), 1.23 - 1.08 (m, 2 H); Ñ (I-8-2), su1H NMR (400 MHz, CDCb) is 68.87 (s, 1 H). 7.92 (d, J = 7.8 Hz, 1H). 7.80 (d, J = 8.0 Hz, 1 H). 7.52 (d, J = 8.4 Hz. 2 H), 7.39 (d, J = 7.6 Hz. 1 H), 7.29 - 7.25 (m, 2 H), 5.82-5.63 ( m, 1 H), 5.12-4.91 (m, 2 H), 4.78 (d, J = 6.2 Hz, 2 H), 4.01 (s, 1 H), 3.17 (S, 4 H) , 2.53 (s, 1 H),2.33 (s, 1 H), 2.06 (d, J = 4.4 Hz, 2 H), 1.89 (d, J = 11.6 Hz, 2 H), 1.75 (re, J = 14.1 Hz, 2 H), 1.59 (re, J = 17.2 Hz, 8 H), 1.46 (t, J = 13.1 Hz, 2 H); (1-15-1), its Ή NMR (400 MHz, MeOD) is δ 8.84 (s, 1 H), 8.04 (t, J .9 Hz, 1 H), 7.92 (d, J = 8.1 Hz , 1 H), 7.67 (d, J = 7.6 Hz, 1 H), 7.60 (d, J = 8.6 Hz, 2 H), 7.21 (d, J = 8.6 Hz, 2 H), 5.78 (ddt, J = 16.3, 10.3, 6.1 Hz, 1 H), 5.12 - 5.05 (m, 3 H), 4.98 (dd, J = 17.1, 1.3 Hz, 1 H), 4.89 (d, J= 6.1 Hz, 2 H), 4.84 (s, 2 H), 3.68 (s, 2 H), 2.97 - 2.86 (m, 1 H), 2.66 (s, 6 H), 2.60-2.50 (m, 1 H), 2.15 (d, J = 8.6 Hz, 2 H), 2.04 (d, J = 9.0 Hz, 2 H), 1.66-1.54 (m, 4 H); HW 'N' MA / t / ZUZZ / UI0400 (1-15-2), its ’H NMR (400 MHz, MeOD) is δ 8.83 (s, 1 H), 8.04 (t, J = 7.9 Hz, 1 H), 7.92 (d, J = 8.0 Hz, 1 H), 7.67 - 7.62 (m, 1 H), 7.59 (d, J = 8.6 Hz, 2 H), 7.29 (d, J = 8.5 Hz, 2 H), 5.76 (ddt, J = 16.3, 10.2, 6.1 Hz, 1 H), 5.10-5.02 (m, 3 H), 4.96 (dd, J = 17, 1, 1.3 Hz, 1 H), 4.87 (d, J = 6.8 Hz, 2 H), 4.82 (d, J = 6.8 Hz, 2 H), 2.73 (d, J = 4.2 Hz, 1 H ), 2.29 (d, J = 21.9 Hz, 7 H), 2.04 - 1.90 (m, 4 H), 1.66 (dd, J = 15.6, 6.1 Hz, 4 H); (1-36-1), su1H NMR (400 MHz, CDCI3) is δ 8.88 (d, J = 2.6 Hz, 1 H), 8.09 (dd, J = 15.0, 7.8 Hz, 1 H), 7.99-7.83 (m, 2 H), 7.54 (t, J = 9.5 Hz, 2 H), 7.39 (d, J = 8.7 Hz, 1 H), 7.21 (d, J = 8.5 Hz, 1 H), 5.74 (dq, J = 10.5, 5.9 Hz, 1 H), 5.12 (t, J = 8.8 Hz, 3 H), 4.99 (d, J = 17.1 Hz, 1 H), 4.80 (d, J = 6.3 Hz, 2 H), 4.67 (d, J = 6.0 Hz, 2 H), 3.39 -3.24 (m, 4 H), 2,602.34 (m, 3 H), 2.14 (dt, J = 14.0, 6.8 Hz, 3 H), 1.96 (d, J = 10.8 Hz, 4 H) , 1.55-1.37 (m, 2 H), 1.27-1.12 (m, 2 H); (I-36-2), su1H NMR(400 MHz, MeOD) is δ 8.86 (s, 1 H), 8.02 (dt, J = .0, 7.9 Hz, 3 H), 7.64 (dd, J = 27, 1, 8.1 Hz, 3 H), 7.27 (t, J = 8.6 Hz, 2 H), 7.01- 6.91 (m, 3 H), 6.72-6.64 (m, 3 H), 5.79 (ddd, J = 16.3, 11.2, 6.1 Hz, 1H), 5.10-5.05 (m, 2H), 4.85 (d, J = 6.8 Hz, 2H), 2.57 (d, J = 10.7 Hz, 1H) , 2.48-2.28 (m, 3H), 2.23-2.06 (m, 3H), 1.98-1.71 (m, 6H), 1.58 (dd, J = 23.2, 12.9 Hz, 3 H), 1.44 (ddd, J = 16.1, 13.2, 3.5 Hz, 2H), 1.19-1.00 (m,2H); (1-41 -1), su1H NMR(400 MHz, chloroform-d) is δ 9.00 (s, 1 H), 8.30 (d, J = 8.6 Hz, 1 H), 8.22 (d, J = 2.4 Hz, 1 H), 7.96 (t, J = 7.9 Hz, 1 H), 7.73 (dd, J = 8.1,0.8 Hz, 1 H), 7.55 (dd, J = 8.7, 2.4 Hz, 1 H), 7.44 (dd, J = 7.7, 0.8 Hz, 1 H), 5.77 - 5.66 (m, 1 H) ), 5.12 5.05 (m , 1H), 4.97 (dq, J = 17.0, 1.4 Hz, 1H), 4.76 (dt, J = 6.3, 1.3 Hz, 2H), 2.70 (s, 1H), 2.56 (s , 6H), 2.23 (q, J = 9.5 Hz, 4 H), 2.11 -2.01 (m,4H), 1.58(1, J= 10.3 Hz, 6 H); (1-41-2), su1H NMR (400 MHz, chloroform-d) is 58.99 (s, 1 H), 8.54 (s, H), 8.32 (d, J = 8.7 Hz, 1 H), 8.26 (d, J = 2.4 Hz, 1 H), 8.10 (t, J = 7.7 Hz, 1 H), 7.92 (s, 1 H), 7.78 (dd, J = 8.1,0.8 Hz, 1 H), 7.47-7.41 (m, 1 H), 5.79-5.71 (m, 1 H), 5.08 (dq, J = 10.1, 1.2 Hz, 1 H), 4.97 (dq, J = 17.0, 1.3 Hz, 1 H), 4.77 (dt, J = 6.2, 1.4 Hz, 2 H), 3.99 (s, 1 H), 2.75 (d, J= 11.0 Hz, 1 H), 2.52 (S, 6 H), 2.32 - 2.18 (m, 1 H), 2.09 ( d, J = 14.4 Hz, 4H), 1.31 (d, J = 22.8 Hz, 4H); where, / means that the ds-trans conformation is uncertain. In certain scheme, in the pyrazolopyrimidine compound represented by formula II, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof or the prodrug thereof, the compound pyrazolopyrimidine represented by formula II is any of the following compounds: 8-1), su1H NMR (400 MHz, CDCH) has a peak of 1.23-1.08; where, / means that the cis-trans conformation is uncertain. In a certain scheme, in the pyrazolopyrimidine compound represented by formula II, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof or the prodrug thereof, the compound pyrazolopyrimidine represented by formula II is any of the following compounds: either Η Ν’^'Ί'Γ'Ν OH IVIA / t / ZUZZ / U I0400 (1-1-1) with a retention time of 10.55 min under the following conditions: Agilent 1260 high-performance liquid chromatograph; mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; column time; 15 minutes; column type: Waters' Xseiect, 5 pm, 4.6x250 mm; gradient elution, 5% mobile phase B 50% mobile phase B; HN' OH (M-2) with a retention time of 10.78 min under the following conditions: Agilent 1260 high-performance liquid chromatograph; mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; column time: 15 minutes; column type: Waters' Xseiect, 5 pm, 4.6x250 mm; gradient elution, 5% mobile phase B -> 50% mobile phase B; p / = II J HN N N OH ,N ''—I (1-3-1) with a retention time of 11.01 min under the following conditions: Agilent 1260 high-performance liquid chromatograph; mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; column time: 15 minutes; column type: Waters' Xseiect, 5 pm, 4.6x250 mm; gradient elution, 5% mobile phase B > 50% mobile phase B; V-7 (Ι-3-2) with a retention time of 11.20 min under the following conditions: Agilent 1260 High Performance Liquid Chromatograph; mobile phase A; water (0.1% ai formic acid), mobile phase B: acetonitrile; column time: 15 minutes; column type: Waters' Xselect, 5 pm, 4.6x250 mm; gradient elution, 5% mobile phase B —> 50% mobile phase B; TO V (1-8-1) with a retention time of 10.78 min under the following conditions: Agilent 1260 high-performance liquid chromatograph; mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; column time: 15 minutes: column type: Waters' Xselect, 5 pm, 4.6x250 mm; gradient elution, 5% mobile phase B -> 50% mobile phase B; either (1-8-2) with a retention time of 11.00 min under the following conditions: Agilent 1260 high-performance liquid chromatograph; mobile phase A: water (0.1% ai formic acid), mobile phase B: acetonitrile; column time: 15 minutes; column type: Waters' Xselect, 5 pm, 4.6x250 mm; gradient elution, 5% mobile phase B -> 50% mobile phase B; (1-15-1) with a retention time of 7.02 min under the following conditions: High performance liquid chromatograph Agüen! 1260; mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; column time: 15 minutes; column type: Waters' Xselect, 5 pm, 4.6x250 mm; gradient elution, 5% mobile phase B 95% mobile phase B; EITHER ΗΝ^Ν' N A A re TO ΜΛ / Ε / ΖυΖΖ / υΊ 0400 w (1-15-2) with a retention time of 7.16 min under the following conditions: Agilent 1260 high-performance liquid chromatograph; mobile phase A: water (0.1% ai formic acid), mobile phase B: acetonitrile; column time: 15 minutes; column tie type: Waters' Xselect, 5 pm, 4.6x250 mm; gradient elution, 5% mobile phase B > 95% mobile phase B; (1-36-1) with a retention time of 7.14 min under the following conditions: Agilent 1260 high-performance liquid chromatograph; mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; column time: 15 minutes; column type: Waters' Xselect, 5 pm, 4.6x250 mm; gradient elution, 5% mobile phase B -> 95% mobile phase B; (1-36-2) with a retention time of 7.15 min under the following conditions: Agilent 1260 high-performance liquid chromatograph; mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; column time: 15 minutes; column type: Waters' Xselect, 5 pm, 4.6x250 mm; gradient elution, 5% mobile phase B > 95% mobile phase B; ^-Ν·ν (1-41-1) with a retention time of 6.17 min under the following conditions: Agüent 1260 high-performance liquid chromatograph; mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; column time: 15 minutes; column type: Waters' Xseiect, 5 μm, 4.6x250 mm; gradient elution, 5% mobile phase B —> 95% mobile phase B; (1-41-2) with a retention time of 6.28 min under the following conditions: Agilent 1260 high-performance liquid chromatograph; mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; column time: 15 minutes; column type: Waters' Xseiect, 5 pm, 4.6x250 mm; gradient elution, 5% mobile phase B -> 95% mobile phase B; where, 'Zmeans that the cis-trans conformation is uncertain. In certain scheme, in the pyrazolopyrimidine compound represented by formula II, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof or the prodrug thereof, the compound pyrazolopyrimidine represented by formula II is any of the following compounds: EITHER QQfrQ I Π / 77Π7 / 3 / ΥΙΛ The present disclosure also provides a method of preparing the compound. II, the method is any of the following methods: method 1, comprising the following steps: step I, oxidizing compound 11-1A by an oxidant in an organic solvent to obtain compound II-1B; step II, reaction compound 11-1B with compound 11-1C in an organic solvent and under alkaline conditions to obtain compound II; method 2, comprising the following steps: step I, hydrolyzed compound II-2A (R1es -(C = O)-OC2H5) to obtain compound II-2B (R1es -(C = O)-OH); Step II, a condensation reaction is carried out between compound II-2B and an amino compound in an organic solvent to obtain compound II (R1es -(C = Oj-NR1·5^1'5'2). The reaction conditions and steps described in method 1 may be conventional conditions and steps in the art. The following reaction conditions are particularly preferred in the present disclosure: Step 1, the organic solvent is preferably one or more of methane, dichloromethane, acetonitrile, toluene and DMF, more preferably dichloromethane or toluene; the oxidant may be an oxidant commonly used in the art to oxidize the thioether to sulfoxide, preferably m-cyoroperoxybenzoic acid (m-CPBA); the molar ratio of compound 11-1A to m-CPBA is preferably 1: (1-1.2), the reaction time is preferably 1 to 12 hours, and the reaction temperature is preferably 0 ° C to 35 ° C . Step 2, the organic solvent is preferably dichloromethane or toluene; the alkaline condition is preferably an organic base such as N, / V-diisopropylethylamine (DIPEA) or triethylamine, more preferably N, / V-diisopropylethylamine (DIPEA); the molar ratio of compound II-1B, compound II-1C and DIPEA is preferably 1:1:2, the reaction time is preferably 0 to 12 hours, and the reaction temperature is preferably 0 ° C to 35 ° C . The reaction conditions and steps described in method 2 may be conventional conditions and steps in the art. The following reaction conditions are particularly preferred in the present disclosure; Step I, hydrolysis reaction conditions are any suitable reaction conditions commonly used in the art, such as alkaline hydrolysis or acid hydrolysis, and alkaline hydrolysis is, for example, sodium hydroxide hydrolysis or lithium hydroxide hydrolysis. Step II, the amino compound can be a primary or secondary amine; the organic solvent is preferably dichloromethane or DMF; The condensation reaction is carried out under any suitable reaction conditions commonly used in the art, such as EDCI / HOBT / DIPEA or HATU / DIPEA. The present disclosure also provides a compound represented by formula II-1C: TO 8-8C where, X is CH or N, A is defined as above. In some scheme, the compound represented by formula 11-1C may be any of the following compounds: In one scheme, the compound represented by formula 11-1C may be any of the following compounds: , su1H NMR (400 MHz, CDCI3) is δ 7.08 - 6.96 (m, 2H), 6.70 - 6.60 (m, 2H), 3.57 (s, 2H), 3.22 (t, J = 7.0 Hz, 4H), 2.38 (tt, J = 12.1, 3.2 Hz, 1H), 2.15 1.95 (m, 5H ), 1.95 - 1.81 (m, 4H), 1.51 - 1.30 (m, 2H), 1.21 - 1.04 (m, 2H); H2N, su1H NMR (400 MHz, MeOD) is δ 7.10 - 6.97 (m, 2 H), 6.74 - 6.63 (m, 2 H), 4.22 - 4.08 (t, J = 8.0 Hz, 4 H), 3.47 - 3.38 (m, 1 H), 2.61 - 2.52 ( m, 1H), 2.52 - 2.28 (m, 2H), 1.92 - 1.62 (m, 8H). The present disclosure also provides a method of preparing the compound represented by formula 11-1C, the method being any of the following methods: method A: step I, protection of the amino N of compound 11-1C1 in an organic solvent under alkaline conditions to obtain compound 11-1C2; step II, a Suzuki reaction is carried out between compound 11-1C2 and compound 11-1C3 to obtain compound ¡1-1C4; step III, eliminate the ketal from compound IÍ-1C4 to obtain compound II1C5; step IV, a reductive amination reaction is carried out with compound 11-1C5 to obtain compound 11-1C6; step V, removing the amino protecting group PG with a reducing agent and reducing the double bond simultaneously to obtain the compound lí1C; Wherein PG is an amino protecting group, R1 is -NR1'3R1! and R1'3 and R14 are defined as above; method B, which comprises the following steps: step I, a Suzuki reaction is carried out between the compound Π-1C and the compound 11-1C2' to obtain the compound 11-1C3'; step II, a reduction reaction is carried out with compound II-1C3' to obtain compound 11-1C; IMCT S-1C31 Step ii where, R1 is -C (= O) R15, R1'5 is defined as above; method C, which comprises the following steps: step I, a reductive amination reaction is carried out with the compound II-1C1 (ring A is οχο-Ο4-Ο6cycioalkyl) to obtain the compound II-1C2 (R1es -NR^ R1'4); step II, a Buchwald reaction is carried out between the compound 11-1C2” and benzophenone imine to obtain the compound H-1 C3 (R1es-NR13R14); step III, remove diphenyl from compound 11-1C3 to obtain compound II-1C; where, A, R1'3 and R1'4 are defined as above. The reaction conditions and steps described in method A may be conventional conditions and steps in the art. The following reaction conditions are particularly preferred in the present disclosure: Step I, the PG amino protecting group may be any suitable amino protecting group commonly used in the art, preferably Cbz, which is intended to protect compound 11-1C1 from certain reactive groups (e.g., amino groups) when involved. in the reaction. The compound 11-1C1 is preferably a bromide or an iodide. Step II, Suzuki reaction conditions are any suitable reaction conditions commonly used in the art. The Suzuki reaction conditions are preferably Pd(Ph3PAGS)4 or Pd(dppf)Cb, potassium carbonate, 1,2-dimethoxyethane or dioxane. Step III, the ketal removal conditions are any suitable reaction conditions commonly used in the art, the removal is preferably carried out using hydrochloric acid and the reaction temperature is preferably 50°C-100°C. Step IV, the reductive amination reaction conditions are any suitable reaction conditions commonly used in the art, and the reducing agent is preferably sodium triacetoxyborohydride. Step V, the conditions for removing the PG amino protecting group with the reducing agent and simultaneously reducing the double bond may be the conventional method conditions in the art. The amino protecting group PG, such as benzyl or Cbz, preferably Cbz. The reducing agent is preferably palladium on carbon / hydrogen. The reaction conditions and steps described in method B may be conventional conditions and steps in the art. The following reaction conditions are particularly preferred in the present disclosure: Step I, Suzuki reaction conditions are any suitable reaction conditions commonly used in the art. The Suzuki reaction conditions are preferably Pd(Ph3PAGS)4 or Pd(dppf)Cl2, potassium carbonate, 1,2-dimethoxyethane or dioxane. Step II, reduction reaction conditions are any suitable reaction conditions commonly used in the art to reduce both nitro and double bonds, such as palladium carbon / hydrogen, palladium carbon / ammonium formate, palladium carbon / hydrazine hydrate . The reaction conditions and steps described in method C may be conventional conditions and steps in the art. The following reaction conditions are particularly preferred in the present disclosure: Step I, the reductive amination reaction conditions are any suitable reaction conditions commonly used in the art, and the reducing agent preferably sodium triacetoxyborohydride. In step II, the Buchwald reaction conditions are any suitable reaction conditions commonly used in the art. The Buchwald reaction conditions are preferably Pd2(dba)3 / sodium ferf-butoxide / Binap. Step III, the reaction conditions for removing diphenyl are any suitable reaction conditions commonly used in the art, and the reaction conditions are preferably sodium acetate / hydroxylamine hydrochloride. The present disclosure also provides a method of preparing the compound, i, which is any of the following methods: method 1, comprising the following steps: step I, the oxidizing compound 1A with an oxidant in an organic solvent to obtain compound IB; step II, react compound 1B with compound 1C in an organic solvent and under alkaline conditions to obtain compound I; method 2, which comprises the following steps: step I, hydrolyzed compound 2A (R1es -(C = O)-OC2H5) to obtain compound 2B (R1es -(C = O)-OH); step II, a condensation reaction is carried out between compound 2B and an amino compound in an organic solvent to obtain compound I (R1es -(C = Oj-NR1·5^1·5'2); The reaction conditions and steps described in method 1 may be conventional conditions and steps in the art. The following reaction conditions are particularly preferred in the present disclosure: Step 1, the organic solvent is preferably one or more of methanol, dichloromethane, acetonitrile, toluene and DMF, more preferably dichloromethane or toluene; the oxidant may be an oxidant commonly used in the art to oxidize the thioether to sulfoxide, preferably m-chloroperoxybenzoic acid (m-CPBA); the molar ratio of compound 1A to m-CPBA is preferably 1: (1-1.2), the reaction time is preferably 1 to 12 hours, and the reaction temperature is preferably 0 ° C to 35 ° C. Step 2, the organic solvent is preferably dichloromethane or toluene; the alkaline condition is preferably an organic base such as / V, / V-diisopropylethylamine (DIPEA) or triethylamine, more preferably N, / V-diisopropylethylamine (DIPEA); the molar ratio of compound 1B, compound 1C and DIPEA is preferably 1:1:2, the reaction time is preferably 0 to 12 hours, and the reaction temperature is preferably 0 ° C to 35 ° C. The reaction conditions and steps described in method 2 may be conventional conditions and steps in the art. The following reaction conditions are particularly preferred in the present disclosure: Step 1, hydrolysis reaction conditions are any suitable reaction conditions commonly used in the art, such as alkaline hydrolysis or acid hydrolysis, and alkaline hydrolysis is, for example, sodium hydroxide hydrolysis or lithium hydroxide hydrolysis. Step 2, the amino compound can be a primary or secondary amine; the organic solvent is preferably dichloromethane or DMF; The condensation reaction is carried out under any suitable reaction conditions commonly used in the art, such as EDCI / HOBT / DIPEA or HATU / DIPEA. The present disclosure also provides a compound represented by formula 1C: ΝΗ2 QQfrQ I 0 / 7707 / 3 / ΥΙΛ where, A is C3-C20 cycloalkyl substituted by a R1, R' is -NR1'3R1'4o -C (= O) R1'5y the R1'3, ri-4 and R1 -5sec as above. In some scheme, the compound represented by formula 1C may be any of the following compounds: In some scheme, the compound represented by formula 1C may be any of the following compounds: , its ’H NMR (400 MHz, CDCh) is δ 7.08 - 6.96 (m, 2H), 6.70 - 6.60 (m, 2H), 3.57 (s, 2H), 3.22 (t, J = 7.0 Hz, 4H), 2.38 (tt, J = 12.1, 3.2 Hz, 1H), 2.15 1.95 (m, 5H ), 1.95 - 1.81 (m, 4H), 1.51 - 1.30 (m, 2H), 1.21 - 1.04 (m, 2H); H2N— / and, its ’H NMR (400 MHz, MeOD) is δ 7.10 - 6.97 (m, 2H), 6.74 - 6.63 (m, 2H), 4.22 - 4.08 (t, J = 8.0 Hz,, 4H), 3.47 - 3.38 (m, 1H), 2.61 - 2.52 (m, 1H)), 2.52 - 2.28 (m, 2H), 1.92-1.62 (m, 8H). The present disclosure also provides a method of preparing the compound represented by formula 1C, which is any of the following methods: method A: step I, protection of the amino N of compound 1C1 in an organic solvent under alkaline conditions to obtain compound 1C2; step II, a Suzuki reaction is carried out between compound 1C2 and compound 1C3 to obtain compound 1C4; step III, remove the ketal from compound 1C4 to obtain compound 1C5; step IV. a reductive amination reaction is carried out with compound 1C5 to obtain compound 1C6; Step V, remove the PG amino protecting group from compound 1C6 with a reducing agent and reducing the double bond simultaneously to obtain compound 1C; FORM ÍEACCSJR 1 wherein PG is an amino protecting group, R1 is -NR1'3R1'4 and R1'3 and R1* are defined as above; method B, which comprises the following steps: step I, a Suzuki reaction is carried out between compound 1C and compound 102' to obtain compound 103'; step II, a reduction reaction is carried out with compound 103' to obtain compound 1C; 1CT 103'ic Resection Form 2 where, R1 is -C (= O) R1'5, R15 is defined as above; method C, which comprises the following steps: step I, a reductive amination reaction is carried out with compound 1C1 (ring A is oxo-C4-Cs cycloalkyl) to 3Q obtain compound 1C2 (R1es-NR^R1' ); step II, a Buchwald reaction is carried out between compound 1C2 and benzophenone mine to obtain compound 1C3 (R1es -NR! 3R; 4); step ΙΠ, remove diphenyl from compound 1C3” to obtain compound 1C; QQbQ I η / 77Π7 / =1 / ΥΙΛ where, A, R1'3and R·'4are defined as above. The conditions and steps of the reaction described in method A may be 10 conventional conditions and steps in the art. The following reaction conditions are particularly preferred in the present disclosure: Step I, the PG amino protecting group may be any suitable omino protecting group commonly used in the art, preferably Cbz, which is intended to protect compound 1C1 from certain reactive groups (e.g., amino groups) when involved in the reaction. Compound 1C1 is preferably a bromide or an iodide. Step II, Suzuki reaction conditions are any suitable reaction conditions commonly used in the art. The Suzuki reaction conditions are preferably Pd(PhsPAGS)4 or Pd(dppf)Cb, potassium carbonate, 1,2-dimethoxyethane or dioxane. Step III, the ketal removal conditions are any suitable reaction conditions commonly used in the art, the removal is preferably carried out using hydrochloric acid and the reaction temperature is preferably 50°C-100°C. Step IV, the reductive amination reaction conditions are any suitable reaction conditions commonly used in the art, and the reducing agent is preferably sodium triacetoxyborohydride. Step V, the conditions for removing the PG amino protecting group with the reducing agent and simultaneously reducing the double bond may be the conventional method conditions in the art. The amino protecting group PG, such as benzyl or Cbz, preferably Cbz. The reducing agent is preferably palladium on carbon / hydrogen. The reaction conditions and steps described in method B may be conventional conditions and steps in the art. The following reaction conditions are particularly preferred in the present disclosure: Step I, Suzuki reaction conditions are any suitable reaction conditions commonly used in the art. The Suzuki reaction conditions are preferably Pd(Ph3PAGS)4 or Pd(dppf)Cl2, potassium carbonate, 1,2-dimethoxyethane or dioxane. Step II, reduction reaction conditions are any suitable reaction conditions commonly used in the art to reduce both nitro and double bonds, such as palladium carbon / hydrogen, palladium carbon / ammonium formate, palladium carbon / hydrazine hydrate . The reaction conditions and steps described in method C may be conventional conditions and steps in the art. The following reaction conditions are particularly preferred in the present disclosure: Step I, the reductive amination reaction conditions are any suitable reaction conditions commonly used in the art, and the reducing agent is preferably sodium triacetoxyborohydride. Step II, Buchwald reaction conditions are any suitable reaction conditions commonly used in the art. The Buchwald reaction conditions are preferably Pd2(dba)3 / sodium ferf-butoxide / Binap. Step III, the reaction conditions for removing diphenyl are any suitable reaction conditions commonly used in the art, and the reaction conditions are preferably sodium acetate / hydroxylamine hydrochloride. The present disclosure also provides an application of a substance X in the preparation of kinase inhibitors (such as WEE1 kinase); Substance The present disclosure also provides an application of substance X in the manufacture of a medicament; Substance The present disclosure also provides an application of substance X in the manufacture of a medicament; the drug is used to treat and / or prevent diseases related to WEE1 kinase; Substance Diseases related to WEE1 kinase such as cancer. Cancers are, for example, brain cancer, head and neck cancer, esophageal cancer, thyroid cancer, small cell cancer, non-small cell cancer, breast cancer, lung cancer, stomach cancer, cholangiocarcinoma. gallbladder, liver cancer, cancer ΊΛ / t / ZUZZ / U I0400 pancreatic cancer, colon cancer, rectal cancer, ovarian cancer, choriocarcinoma, endometrial carcinoma, cervical cancer, renal peivis-ureteral cancer, bladder cancer, prostate cancer, kidney cancer penis, testicular cancer, embryonal carcinoma, nephroblastoma, skin cancer, malignant melanoma, neuroblastoma, osteosarcoma, Ewing's tumor, soft tissue tumor, acute leukemia, chronic lymphatic leukemia, chronic myeloid leukemia or Hodgkin's lymphoma, for example, cancer breast, lung cancer, pancreatic cancer, colon cancer, ovarian cancer, acute leukemia, chronic lymphatic leukemia, chronic myeloid leukemia, Hodgkin lymphoma, for example, colon or ovarian cancer. The present disclosure also provides an application of substance X in the manufacture of a medicament; the drug is used to treat and / or prevent cancer; Substance Cancers are, for example, brain cancer, head and neck cancer, esophageal cancer, thyroid cancer, small cell cancer, non-small cell cancer, breast cancer, lung cancer, stomach cancer, cholangiocarcinoma. gallbladder, liver cancer, pancreatic cancer, colon cancer, rectal cancer, ovarian cancer, choriocarcinoma, endometrial carcinoma, cervical cancer, renal peivis-ureteral cancer, bladder cancer, prostate cancer, cancer of the penis, testicular cancer, embryonal carcinoma, nephroblastoma, skin cancer, malignant melanoma, neuroblastoma, osteosarcoma, Ewing's tumor, soft tissue tumor, acute leukemia, chronic lymphatic leukemia, chronic myeloid leukemia or Hodgkin's lymphoma, for example, breast cancer, lung cancer, pancreatic cancer, colon cancer, ovarian cancer, acute leukemia, chronic lymphatic leukemia, chronic myeloid leukemia, Hodgkin lymphoma, for example, colon or ovarian cancer. The present disclosure also provides a method of treating and / or preventing WEE1 kinase-related diseases comprising administering a therapeutically effective amount of substance X to a patient; Substance Diseases related to WEE1 kinase such as cancer. Cancers are, for example, brain cancer, head and neck cancer, esophageal cancer, thyroid cancer, small cell cancer, non-small cell cancer, breast cancer, lung cancer, stomach cancer, cholangiocarcinoma. gallbladder, liver cancer, pancreatic cancer, colon cancer, rectal cancer, ovarian cancer, choriocarcinoma, endometrial carcinoma, cervical cancer, renal peivis-ureteral cancer, bladder cancer, prostate cancer, kidney cancer penis, testicular cancer, embryonal carcinoma, nephroblastoma, skin cancer, malignant melanoma, neuroblastoma, osteosarcoma, Ewing's tumor, soft tissue tumor, acute leukemia, chronic lymphatic leukemia, chronic myeloid leukemia or Hodgkin's lymphoma, for example, cancer breast, lung cancer, pancreatic cancer, colon cancer, ovarian cancer, acute leukemia, chronic lymphatic leukemia, chronic myeloid leukemia, Hodgkin lymphoma, for example, colon or ovarian cancer. The present disclosure also provides a method of treating and / or preventing cancer comprising administering a therapeutically effective amount of the substance. X to a patient; Substance Cancers are, for example, brain cancer, head and neck cancer, esophageal cancer, thyroid cancer, small cell cancer, non-small cell cancer, breast cancer, lung cancer, stomach cancer, cholangiocarcinoma. gallbladder, liver cancer, pancreatic cancer, colon cancer, rectal cancer, ovarian cancer, choriocarcinoma, endometrial carcinoma, cervical cancer, renal pelvis-ureteral cancer, bladder cancer, prostate cancer, cancer of the penis, testicular cancer, embryonal carcinoma, nephroblastoma, skin cancer, malignant melanoma, neuroblastoma, osteosarcoma, Ewing's tumor, soft tissue tumor, acute leukemia, chronic lymphatic leukemia, chronic myeloid leukemia or Hodgkin's lymphoma, for example, breast cancer, lung cancer, pancreatic cancer, colon cancer, ovarian cancer, acute leukemia, chronic lymphatic leukemia, chronic myeloid leukemia, Hodgkin lymphoma, for example, colon or ovarian cancer. The present disclosure also provides a pharmaceutical composition comprising substance X and (one or more) pharmaceutical excipients; Substance The present disclosure also provides a combination comprising substance pharmaceutically acceptable thereof, the metaboiite thereof or the prodrug thereof. The anticancer drugs may be an anticancer drug conventional in the art (but not a substance , plant-derived anticancer drugs, anticancer platinum ligand compounds, anticancer camptothecin derivatives, anticancer tyrosine kinase inhibitors, monoclonal antibodies, interferons, biological response modifiers, mitoxantrone, L-asparaginase , procarbazine, dacarbazine, hydroxyurea, peniostatin, retinoic acid, alefacept, darbepoetin alfa, anastrozole, exemestane, bicalutamide, leupralide, flutamide, fulvestrant, pegaptanib sodium, denieukin 2, difotleukin, arsenic trioxide, bortezomib, capecitabine and goserelin, for example, metabolic antagonists against cancer. The anticancer alkylating agent may be an anticancer alkylating agent conventional in the art, such as one or more of mechlorethanmine n-oxide, cyclophosphamide, ifosfamide, melphalan, busulfan, dibromomannitol, carboquone, thiotepa, ranimustine, nimustine, temozolomide and carmustine. The anticancer metabolic antagonist may be a conventional anticancer metabolic antagonist in the art, such as one or more of methotrexate, 6-mercaptopurine nucleoside, mercaptopurine, 5-fluorouracil, tegafur, doxyfluridine, carmofur, cytarabine, cytarabine octadecylite sodium phosphate, enocitabine , S-1, gemcitabine, fludarabine, and pemetrexed disodium, such as 5-fluorouracil. The anticancer antibiotic may be a conventional anticancer antibiotic in the art, such as one or more of actinomycin D, doxorubicin, daunorubicin, neocarzinostatin, bleomycin, peplomycin, mitomycin C, aclarubicin, pirarubicin, epirubicin, zinostatin stimalamer, sirrolustatin, idarrobicin. The plant-derived anticancer drug may be a conventional plant-derived anticancer drug in the art, such as one or more of vincristine, vinblastine, vindesine, etoposide, sobuzoxane, docetaxel, paclitaxel and vinorelbine. The anti-cancer platinum coordination compound may be a conventional anti-cancer platinum coordination compound in the art, such as one or more of cisplatin, carboplatin, nedaplatin and oxaliplatin. The anticancer camptothecin derivative may be an anticancer camptothecin derivative conventional in the art, such as one or more of irinotecan, topotecan and camptothecin. The anticancer tyrosine kinase inhibitor may be a conventional anticancer tyrosine kinase inhibitor in the art, such as one or more of gefitinib, imatinib and erlotinib. The monoclonal antibody may be a monoclonal antibody conventional in the art, such as one or more of cetuximab, bevacizumab, rituximab, alemtuzumab and trastuzumab. The interferon may be a conventional interferon in the art, such as one or more of the interferons. a, interferon a-2a, interferon a-2b, interferon β, interferon y-1a and interferon γ-η1. ΊΛ / t / ZUZZ / U I0400 The biological response regulator may be a conventional biological response regulator in the art, such as one or more polysaccharides of coriolus versicolor, lentinan, sizofiran, sapylin and ubenimex. The components of the combination can be used simultaneously or separately (for example, sequentially); when the components of the combination are used simultaneously, the components of the combination can be mixed uniformly (for example, mixing the components). The components of the combination can be prepared as a single pharmaceutical composition for simultaneous use, or the components can be prepared individually as a single independent pharmaceutical composition (e.g., in kit form), which can be used simultaneously or separately. (e.g., sequentially). . The present disclosure also provides an application of the above combination in the preparation of a medicament for preventing and / or treating cancer. Cancers are, for example, brain cancer, head and neck cancer, esophageal cancer, thyroid cancer, small cell cancer, non-small cell cancer, breast cancer, lung cancer, stomach cancer, cholangiocarcinoma. gallbladder, liver cancer, pancreatic cancer, colon cancer, rectal cancer, ovarian cancer, choriocarcinoma, endometrial carcinoma, cervical cancer, renal pelvic-ureteral cancer, bladder cancer, prostate cancer, cancer of the penis, testicular cancer, embryonal carcinoma, nephroblastoma, skin cancer, malignant melanoma, neuroblastoma, osteosarcoma, Ewing's tumor, soft tissue tumor, acute leukemia, chronic lymphatic leukemia, chronic myeloid leukemia or Hodgkin's lymphoma, for example, breast cancer, lung cancer, pancreatic cancer, colon cancer, ovarian cancer, acute leukemia, chronic lymphatic leukemia, chronic myeloid leukemia, Hodgkin lymphoma, for example, colon or ovarian cancer. In the application of the present disclosure, the above substance X and the above anticancer drugs may be administered simultaneously or separately (e.g., sequentially). The present disclosure also provides a method of treating and / or preventing cancer comprising administering a therapeutically effective amount of the above combination to a patient. The anticancer drug may be as described above. Cancers are, for example, brain cancer, head and neck cancer, esophageal cancer, thyroid cancer, small cell cancer, non-small cell cancer, breast cancer, lung cancer, stomach cancer, cholangiocarcinoma. gallbladder, liver cancer, pancreatic cancer, colon cancer, rectal cancer, ovarian cancer, choriocarcinoma, endometrial carcinoma, cervical cancer, pelvic-ureteral cancer IVIA / t / ZUZZ / U I0400 renal, bladder cancer, prostate cancer, penile cancer, testicular cancer, embryonal carcinoma, nephroblastoma, skin cancer, malignant melanoma, neuroblastoma, osteosarcoma, Ewing tumor, soft tissue tumor , acute leukemia, chronic lymphatic leukemia, chronic myeloid leukemia or Hodgkin lymphoma, for example, breast cancer, lung cancer, pancreatic cancer, colon cancer, ovarian cancer, acute leukemia, chronic lymphatic leukemia, chronic myeloid leukemia, Hodgkin lymphoma, for example colon or ovarian cancer. The present disclosure also provides an application of the above substance. X in the preparation of a medicine, the medicine in combination with an anti-cancer drug is used to prevent and / or treat cancer. The anticancer drug may be as described above. Cancers are, for example, brain cancer, head and neck cancer, esophageal cancer, thyroid cancer, small cell cancer, non-small cell cancer, breast cancer, lung cancer, stomach cancer, cholangiocarcinoma. gallbladder, liver cancer, pancreatic cancer, colon cancer, rectal cancer, ovarian cancer, choriocarcinoma, endometrial carcinoma, cervical cancer, renal pelvic-ureteral cancer, bladder cancer, prostate cancer, cancer of the penis, testicular cancer, embryonal carcinoma, nephroblastoma, skin cancer, malignant melanoma, neuroblastoma, osteosarcoma, Ewing's tumor, soft tissue tumor, acute leukemia, chronic lymphatic leukemia, chronic myeloid leukemia or Hodgkin's lymphoma, for example, breast cancer, lung cancer, pancreatic cancer, colon cancer, ovarian cancer, acute leukemia, chronic lymphatic leukemia, chronic myeloid leukemia, Hodgkin lymphoma, for example, colon or ovarian cancer. In the application of the present disclosure, the above substance X and the above anticancer drugs may be administered simultaneously or separately (e.g., sequentially). The present disclosure also provides an anticancer drug in the preparation of a medicament, the medicament in combination with substance X used to prevent and / or treat cancer. The anticancer drug may be as described above. Cancers are, for example, brain cancer, head and neck cancer, esophageal cancer, thyroid cancer, small cell cancer, non-small cell cancer, breast cancer, lung cancer, stomach cancer, cholangiocarcinoma. gallbladder, liver cancer, pancreatic cancer, colon cancer, rectal cancer, ovarian cancer, choriocarcinoma, endometrial carcinoma, cervical cancer, renal pelvic-ureteral cancer, bladder cancer, prostate cancer, cancer of penis, testicular cancer, embryonal carcinoma, nephroblastoma, skin cancer, malignant melanoma, neuroblastoma, osteosarcoma, ewing tumor, soft tissue tumor, acute leukemia, chronic lymphatic leukemia, leukemia ΊΛ / t / ZUZZ / U I0400 chronic myeloid or Hodgkin lymphoma, for example, breast cancer, lung cancer, pancreatic cancer, colon cancer, ovarian cancer, acute leukemia, chronic lymphatic leukemia, chronic myeloid leukemia, lymphoma Hodgkin's disease, for example, colon or ovarian cancer. In the application of the present disclosure, the above substance X and the above anticancer drugs may be administered simultaneously or separately (e.g., sequentially). The present disclosure also provides a pharmaceutical composition comprising the above combination and (one or more) pharmaceutical excipients. The pharmaceutical composition may be composed of the combination and the pharmaceutical excipients. The present disclosure also provides a drug combination kit comprising a pharmaceutical composition A and a pharmaceutical composition B; The pharmaceutical composition A comprises the above substance X, and (one or more) pharmaceutical excipients; Pharmaceutical composition B comprises the anticancer drugs and one or more pharmaceutical excipients. The anticancer drug may be as described above. The drug combination kit may be composed of pharmaceutical composition A and pharmaceutical composition B. Pharmaceutical composition A may be composed of substance X, and (one or more) pharmaceutical excipients; pharmaceutical composition B may be composed of drugs against e! cancer and one or more pharmaceutical excipients. Each pharmaceutical composition of the drug combination kit can be used simultaneously or separately (for example, sequentially). Unless otherwise specified, the following terms appearing in this specification and in the claims have the following meanings: The term pharmaceutically acceptable means that the salts, solvents, excipients, etc., are generally non-toxic, safe and suitable for patient use. The patient is preferably a mammal, more preferably a human. The term "pharmaceutically acceptable salt" refers to the salt prepared by the compound of the present disclosure and a relatively non-toxic and pharmaceutically acceptable acid or base. When the compound of the present disclosure contains a relatively acidic functional group, a base addition salt can be obtained by contacting the neutral form of the compound with a sufficient amount of a pharmaceutically acceptable base in a pure solution or a suitable inert solvent. The salts IVIA / t / ZUZZ / U I0400 Pharmaceutically acceptable base additions include, but are not limited to, lithium salts, sodium salts, potassium salts, calcium salts, aluminum salts, magnesium salts, zinc salts , bismuth salts, ammonium salts and diethanolamine salts. When the compound of the present disclosure contains a relatively basic functional group, an acid addition sai can be obtained by contacting the neutral form of the compound with a sufficient amount of a pharmaceutically acceptable acid in a pure solution or a suitable inert solvent. Pharmaceutically acceptable acids include inorganic acids, inorganic acids include, but are not limited to, hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, carbonic acid, phosphoric acid, phosphorous acid, sulfuric acid, etc. Pharmaceutically acceptable acids include organic acids, organic acids include, but are not limited to: acetic acid, propionic acid, oxalic acid, isobutyric acid, maleic acid, malonic acid, benzoic acid, succinic acid, octanedioic acid, frans-butenedioic acid, lactic, mandelic acid, italic acid, benzenesulfonic acid, p-toluenesulfonic acid, citric acid, salicylic acid, tartaric acid, methanesulfonic acid, isonicotinic acid, citric acid acid, oleic acid, tannic acid, pantothenic acid, hydrogen tartrate, ascorbic acid, acid gentianic acid, fumaric acid, gluconic acid, saccharic acid, formic acid, ethanesulfonic acid, pamoic acid (i.e. 4,4'-methylene-bis(3-hydroxy-2-naphtho¡ic acid)), amino acid (e.g. ., glutamic acid, arginine), etc. The disclosure contains relatively acidic and basic functional groups, they can be converted into base addition salts or acid addition salts. See Berge et al., Pharmaceutical Salts, Journal of Pharmaceutical Science 66: 1-19 (1977) or Handbook of Pharmaceutical Salts: Properties, Selection and Use (P. Heinrich Stahl and Camille G. Wermuth, ed„ Wiley-VCH, 2002 ). The term solvate refers to a substance formed together with a compound of the present disclosure with a stoichiometric or non-stoichiometric solvent. Solvent molecules in solvates can exist in an ordered or disordered arrangement. Solvents include but are not limited to: water, methanol, ethanol, etc. The terms pharmaceutically acceptable salts and solvates in the terms solvates of pharmaceutically acceptable salts, as described above, refer to the compound of the present disclosure, 1. prepared with a relatively non-toxic, pharmaceutically acceptable acid or base, and 2. formed in combination with a stoichiometric or non-stoichiometric solvent. Solvates of pharmaceutically acceptable salts include, but are not limited to, hydrochloric acid monohydrate or the compound of the present disclosure. The terms compound, pharmaceutically acceptable salt, solvate and pharmaceutically acceptable salt solvate may exist in crystalline or amorphous form. The term crystalline means that the ions or molecules in it are arranged in a defined manner in three-dimensional space in a strictly periodic manner, and have a regular pattern of periodic recurrence at a certain distance; Due to the above periodic arrangement, there may be a variety of crystal forms, that is, the phenomenon of polycrystalline forms. The term amorphous refers to the disordered distribution of ions or molecules, that is, there is no periodic arrangement between ions and molecules. The terms compound, pharmaceutically acceptable salt, solvate and pharmaceutically acceptable sai solvate may exist in the form of a single stereoisomer or a mixture thereof (e.g., racemate), if stereoisomers exist. The term stereoisomer refers to cis-trans isomer or optical isomer. These stereoisomers can be separated, purified and enriched by asymmetric synthesis or chirai separation methods (including but not limited to thin layer chromatography, rotational chromatography, column chromatography, gas chromatography, high pressure liquid chromatography, etc.), and can also be obtained by chiral resolution by bonding (chemical bonding, etc.) or salting (physical bonding, etc.) with other chiral compounds. The term single stereoisomer means that one stereoisomer of a compound of the present disclosure is not less than 95% by mass with respect to all stereoisomers of the compound. The terms compound, pharmaceutically acceptable salt, solvate and pharmaceutically acceptable salt solvate may exist in the form of a single tautomer or a mixture thereof, preferably in the form in which the more stable tautomer predominates. The terms compound, pharmaceutically acceptable salt, solvate and pharmaceutically acceptable salt solvate may exist in their natural abundance or unnatural abundance. Taking the hydrogen atom as an example, its naturally abundant form means that about 99.985% is protium and about 0.015% is deuterium; in the form of unnatural abundance, for example, about 95% of which is deuterium. That is, one or more atoms in the terms compound, pharmaceutically acceptable salt, solvate and pharmaceutically acceptable salt solvate may be atoms that exist in unnatural abundance. When an arbitrary variable (for example, R1-1-1) occurs many times in the definition of a compound, the definition of each position of the variable is independent of the definition of the rest, and their meanings are independent of each other and are not they affect each other. Therefore, if a given group is replaced by one, two or three R1'1'1groups, that is, the group can be replaced by up to three R''Mgroups, the definition of R1'Men this position is independent of that of R1-1'1. Furthermore, the combination of substituents and / or variables is only allowed when the combination produces a stable compound. The term optionally substituted means that it may or may not be substituted. The term halogen refers to fluorine, chlorine, bromine or iodine. The term alkyl refers to a saturated linear or branched monovalent hydrocarbon group having from one to twelve carbon atoms (e.g., Ci-Cs alkyl, e.g., C1-C4 alkyl). Examples of alkyl include, but are not limited to, methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 2-methyl-1-butyl, 2-butyl, 2-methyl-2-propyl, 1-penthiol, 2-pentyl, 3-pentyl, 25-methyl-2-butyl, 3-methyl-2-butyl, 3-methyl-l-butyl, 2-methyl-1-butyl, 1-hexyl, 2-hexyl, 3-hexyl , 2methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 3-methyl-3-pentyl, 2-methyl-3-pentyl, 2,3dimethyl-2-butyl, S.S-dimethyl ^-butyl, 1-heptyl and 1-octyl. The term "alkenyl" refers to a linear or branched monovalent hydrocarbon group having two to twelve carbon atoms with at least one unsaturated position, i.e., a θ sp2carbon-carbon double bond (e.g., C2-C8alkenyl, e.g. , C2-C4alkenyl), and includes groups with cis and iran orientations or E' and Z orientations. Examples include, but are not limited to, vinyl, allyl. The term alkynyl refers to a linear or branched monovalent hydrocarbon group having two to twelve carbon atoms with at least one unsaturated position, i.e., a carbon-carbon sp triple bond (e.g., C2-C6alkynyl, e.g. , C2-C4 alkynyl). Examples include, but are not limited to, ethinyl and propynyl. The term cycloalkyl refers to a saturated or partially unsaturated (containing one or two double bonds) non-aromatic cyclic hydrocarbon group (e.g., C3Cscycloalkyl) with three to twenty carbon atoms, including monocyclic cycloalkyl and ® polycyclic cycloalkyl. The cycloalkyl group contains 3 to 20 carbon atoms, preferably 3 to 12 carbon atoms, more preferably 3 to 6 carbon atoms. Examples of monocyclic cycloalkyl include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cycloundecyl, cyclododecyl, 1-cyclopent-1-en!-2-cyclopentyl, 1-cyclopentyl cyclopent-3-enyl, 5-hexenyl, 1;5cyclohex-1-enyl, 1-cyclohex-2-enyl and 1-cyclohex-3-enyl. Polycyclic cycloalkyl are polycyclic (e.g., bicyclic and tricyclic) cycloalkyl structures, including spiro cycloalkyl, fused cycloalkyl, and bridged cycloalkyl. Where, spiro cycloalkyl refers to a polycyclic group that shares a carbon atom (called a spiro atom) between 5- to 20-membered single rings, which may contain one or more double bonds, but none of the rings have a π electron system. completely conjugated. Preferably 6 to 14 members, more preferably 7 to 10 members. According to the number of cycloalkyl spiro shared between rings, the cycloalkyl spiro is divided into cycloalkyl monospiro, cycloalkyl bispiro or cycloalkyl polyspiro, preferably cycloalkyl monospiro and cycloalkyl bispiro. More preferably 4-membered / 4-membered, 4-membered / 5-membered, 4-membered / 6-membered, 5-membered / 5-membered or 5-membered / 6-membered cycloalkyl15monospiro. Examples of spiro cycloalkyl include, but are not limited to: . Where, fused cycloalkyl refers to 5- to 20-membered polycarbon groups, each ring in the system shares an adjacent pair of carbon atoms with other rings in the system, which may contain one or more double bonds, but none of the Rings have a completely conjugated π electron system. Preferably 6 to 14 members, more preferably 7 to 10 members. According to the number of constituent rings, it can be divided into bicyclic, tricyclic, tetracyclic or poiicyclic fused cycloalkyl, preferably bicyclic or tricyclic, more preferably 5-membered / 5-membered or 5-membered / 6-membered bicyclic cycloalkyl. Examples of fused cycloalkyl include, but are not limited to: . Bridged cycloalkyl refers to a 5- to 20-membered polycyclic group of carbon, any two rings sharing two carbon atoms not directly connected, which may contain one or more double bonds, but none of which have a fully conjugated π electron system. . Preferably 6 to 14 members, more preferably 7 to 10 members. According to the number of constituent rings, it can be divided into bicyclic, tricyclic, tetracyclic or poiicyclic bridged cycloalkyl, preferably bicyclic, tricyclic or tetracyclic, more preferably bicyclic or tricyclic. Examples of bridged cycloalkyl include, but are not limited to: The term heterocycloalkyl refers to a saturated carbocyclic group having 3 to 20 ring atoms, wherein at least one ring atom is a heteroatom independently selected from boron, silicon, oxygen, sulfur, setenium, nitrogen and phosphorus, and the remaining ring atoms are C. The group can be a carbon group or a heteroatom group (i.e., it can be C-linked or N-linked, whenever possible). Examples of heterocyclic groups include, but are not limited to, pyrrolidinyl, tetrahydrofuran, tetrahydrothiophene, tetrahydropyranyl, tetrahydrothiopyranite, piperidinyl, morpholinyl, 4-ttomorpholinyl, thioalkyl and piperazinyl. The fused ring portion, the spiro ring portion, and the bridging ring portion are also included in the scope of this definition. For example, the group derived from tetrahydropyrrole may be tetrahydropyrrole-1-llo (N-linked) or tetrahydropyrrole-3-yl (C-linked). For example, a 3-7 membered monocyclic ring (1-6 carbon atoms and 1-3 heteroatoms selected from N, O, P, B, Si, S and Se, where N, B, P or Se are optionally substituted with one or more oxygen atoms to obtain groups such as NO, ΒΟΗ, PO, PO2, SeO; N may optionally be quaternized; the S atoms may be optionally substituted with one or more oxygen or nitrogen atoms to obtain a group such as SO , SO2, S (= O) (= NRa), S (= NRB) or S (= NRC)2, while Ra, RB and Rc are independently cyano, C1-C7 alkyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl which has 1-4 heteroatoms and one or more heteroatoms of boron, silicon, oxygen, sulfur, selenium, nitrogen and phosphorus, C1-C7 heteroaryl having 1-4 heteroatoms and one or more heteroatoms of boron, silicon, oxygen, sulfur, setenium , nitrogen and phosphorus”, Cs-Cw arite or C1-C7 alkoxy; meanwhile, the -CH2- group can be optionally substituted by -C (= O)-, -C (= S)- or C (= NRD) -, RDes independently cyano, C1-C7 alkyl, C3-CMcycloalkyl, C3-C14 heterocycloalkyl having 1-4 heteroatoms and one or more heteroatoms of boron, silicon, oxygen, sulfur, setenium, nitrogen and phosphorus, C1-C7 heteroaryl which has 1-4 heteroatoms and one or more heteroatoms of boron, silicon, oxygen, sulfur, setenium, nitrogen and phosphorus, Ce-Ci0aryl or C1-C7 alkoxy; when the ring is a 3-membered ring, there is only one heteroatom present in the ring, or a bicyclic ring consisting of 7 to 10 atoms (4 to 9 carbon atoms and 1-3 heteroatoms selected from N, O, P, B, Si, S, where N, S, B or P is optionally substituted with one or more oxygen atoms to obtain groups such as NO, BOH, SO, SO2, PO, PO2, SeO, while -CH2- group can be optionally substituted with -C (= O)-). Depending on the structure, the heterocyclyl can be a monovalent group or a divalent group, that is, a subheterocyclyl. The term aryl refers to any stable monocyclic or bicyclic carbon ring with up to 10 atoms in each ring, in which at least one of the atoms is an aromatic ring. Examples of the above aryl units include phenyl, naphthyl, tetrahydronaphthyl, 2,3dihydroindenite, biphenyl, phenanthrenyl, anthryl or acenaphthite. It will be understood that in the event that the aryl substituent is a bicyclic substituent and one of the rings is a non-aromatic ring, the connection is made through the aromatic ring. The term heteroaryl refers to a stable monocyclic or bicyclic ring with up to 7 atoms in each ring, where at least one ring is an aromatic ring and contains 1-4 heteroatoms selected from boron, silicon, oxygen, sulfur, selenium, nitrogen, and match. Heteroaryl within this definition includes, but is not limited to: acridinyl, carbazolyte, cinolinyl, quinoxalinyl, pyrazolyl, indolyl, benzofriazolyl, furanyl, thienyl, benzothienite, benzofuranyl, quinolyl, isoquinolite, oxazolyl, isoxazolyl, indolyl, pyrazinyl, pyrazinyl pyrimidinyl, pyrimidinyl, pyrrolyl, tetrahydroquinolite. It should also be understood that heteroaryl includes any IVIA / t / ZUZZ / U I0400 derived from N-oxide of a nitrogen-containing heteroaryl. In the case where the heteroaryl substituent is a bicyclic substituent and a ring is a non-aromatic ring or does not contain heteroatoms, it can be understood that the connections are made through aromatic rings respectively. Heteroaromatic ring-fused aromatic ring systems and bicyclic heteroaromatic ring systems can fuse to form rings. Where, N, S, B, P or Se are optionally substituted with one or more oxygen atoms to obtain groups such as NO, SO, SO2, BOH, PO, PO2, SeO and the N atom can be quaternized. Heteroaryl can join the backbone at any heteroatom or carbon atom to form stable compounds. Depending on the structure, heteroaryl can be a monovalent group or a divalent group, i.e. heteroarylene. The term alkoxy refers to an alkyl linked by an oxygen bridge; alkyl is defined as before. The term alkylthiol refers to an alkyl linked by a sulfur bridge; The alkyl is defined as before. The term cis-trans indeterminate conformation refers to oís or trans. The term component refers to each component of the combination of the present disclosure, that is, the compound represented by formula I (or the compound represented by formula II), the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof or the prodrug thereof, or the anticancer drug. The term pharmaceutical excipients refers to excipients and additives used in the production of drugs and prescription formulation, and refers to all substances contained in pharmaceutical preparations except the active ingredients. See Pharmacopoeia of the People's Republic of China (2015 Edition), Part IV or Manual of Pharmaceutical Excipients (Raymond C Rowe, 6th Edition 2009). The term treatment refers to therapeutic therapy. When referring to a specific condition, treatment means (1) alleviating one or more biological manifestations of the disease or condition, (2) interfering with (a) one or more points in the biological cascade that causes or contributes to the condition, or ( b) one or more biological manifestations of the condition, (3) improve one or more symptoms, effects or side effects associated with the condition or its treatment, or one or more symptoms, effects or side effects, or (4) slow the development of the condition or one or more biological manifestations of the condition. The term prevention refers to a reduction in the risk of acquiring or developing diseases or disorders. The term "therapeutically effective amount" refers to the amount of a compound that is sufficient to effectively treat the diseases or disorders described herein. IVIA / t / ZUZZ / U I0400 document when administered to a patient. The therapeutically effective amount will vary depending on the compound, the condition and its severity, and the age of the patient being treated, but can be adjusted as necessary by those skilled in the art. The term patient refers to any animal, preferably a mammal, preferably a human, to which the compound or composition is to be administered or has been administered according to an embodiment of the present disclosure. The term mammal includes any mammal. Examples of mammals include, but are not limited to, cattle, horses, sheep, pigs, cats, dogs, mice, rats, rabbits, guinea pigs, monkeys, humans, etc., with humans being the most preferred. The term active ingredient refers to the active ingredient in the pharmaceutical composition or combination kit of the present disclosure, that is, the compound represented by formula I (or the compound represented by formula II), the pharmaceutically acceptable state thereof , the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof or the prodrug thereof, the anticancer drug or a combination thereof. On the basis of not violating common sense in the field, the above preferred conditions can be arbitrarily combined to obtain the preferred embodiments of the present disclosure. The reagents and raw materials used in the present disclosure are commercially available. The positive progressive effect of the present disclosure is that: the compounds of the present disclosure have better inhibitory activity against WEE1 kinase and have better bioavailability. DETAILED DESCRIPTION OF THE IMPLEMENTATION. The present disclosure will be further illustrated below by means of embodiments, but is not limited to the scope of the embodiments. Experimental methods not specified in the specific conditions in the following embodiments are selected according to conventional methods and conditions, or according to product specifications. The structures of all compounds of the present disclosure can be identified by nuclear magnetic resonance (1H NMR) and / or mass spectrometry (MS). ΈΙ chemical shift of Ή NMR(ó) was recorded in PPM (10'H. NMR was performed using a Bruker AVANCE-400 spectrometer. LC-MS was determined using an Agilení 1200HPLC / 6120 mass spectrometer. HPLC was determined using Agilent 1260 high-performance liquid chromatograph. Specific HPLC conditions: mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; column time: 15 minutes; column type: Waters' Xseiect, 5 μm, 4.6x250 mm. The thin film silica gel plate was Liangchen HSGF254 silica source or Qingdao GF254 silica gel plate. Column chromatography generally uses 200-300 mesh silica gel Yanta! Huanghai as a carrier. Realization 1 ΊΛ / t / ZUZZ / U I0400 Step 1: 4-Bromoaniline (I-I-a) (58.1 mmoi) was dissolved in toluene (250 ml); Potassium carbonate (87.2 mmol) and benzyl chloroformate (87.2 mmol) were added to the reaction mixture and the reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was filtered, the filtrate was evaporated to dryness to obtain a crude product, and the crude product was washed with ethyl acetate to obtain the target compound (4-bromophenyl)benzyl carbamate (l-1-b) (15 .2 g, 85.4%) as a gray solid. LC-MS: m / z: (MH)= 307.0. Step 2: Benzyl (4-bromophenyl) carbamate (16.0 mmol) (l-1-b) was dissolved in 1,2dimethoxyethane (50 ml); and 4.4.5,546ίΓ3ΠΊθϋΙ-2-(1,4^ίοχ3θ3ρίΓθ [4.5] dec-7-en-8-yl)-1.3,2dioxaborolane (represented by formula 1-1 -c) (16.0 mmol), carbonate were added of sodium (42.0 mmol) and tetrakis(triphenylphosphine)palladium (1.6 mmol) to the reaction mixture, the reaction mixture was heated to 80 °C and stirred for 16 hours. The reaction mixture was filtered, the filtrate was evaporated to dryness to obtain a crude product, and the crude product was purified by column chromatography (dichloromethane / methanol = 100 / 0-95 / 5) to obtain the target compound benzyl (4- (1,4-dioxaspiro[4.5]dec-7-en-8-yl)phenyl)carbamate (l-1-d) (5.6 g, 94%) as a white solid. LC-MS: m / z: (MH)= 366.2. Step 3: Benzyl (4-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)phenyl)carbamate (1-1-d) (15 mmol) was dissolved in tetrahydrofuran (15 ml). Hydrochloric acid (30.0 ml, 4 N) was added to the reaction mixture and the reaction mixture was stirred at 50 °C for 16 hours. The pH value of the reaction mixture was adjusted to 9 with potassium carbonate, then the mixture was extracted with dichloromethane, the organic phase was washed with saturated saline solution, dried over anhydrous sodium sulfate, filtered and evaporated until dried to obtain the crude target compound benzyl (4'-oxo2 3',4 5'-tetrahydro-[1,1'-biphenii]-4-yl)carbamate (l-1-e) (4.0 g, 81% ) as a yellow solid. LC-MS: m / z: (MH)= 322.1. Stage 4: Benzyl (4'-oxo-2 3',4 5'4etrahydro-[1,Γ-biphenyl]-4-yl)carbamate (l-1-e) (12.0 mmol) was dissolved in dichloromethane (25 mL). , dimethylamine hydrochloride (25.0 mmol) and diisopropylethylamine (25.0 mmol) were added to the reaction mixture, and the reaction mixture was stirred at room temperature for 2 hours, and sodium triacetoxyborohydride (37.0 mmol) was added to the mixture. reaction, then the reaction mixture was stirred at room temperature for 16 hours. The pH value of the mixture was adjusted to 9 by adding saturated aqueous potassium carbonate solution and the mixture was extracted with dichloromethane; then the organic phase was washed with saturated saline, dried over anhydrous sodium sulfate, filtered and evaporated to dryness to obtain a crude product, and the crude product was purified by column chromatography (dichloromethane / methanol = 100 / 0 -95 / 5) to obtain the target compound (4!-(dimethylamino)-2',34',5'-tetrahydro-[1,1'-biphenyl]-4-yl)benzyl carbamate (l-1- f) (3.5 g, 80%) as a yellow solid. LC-MS: m / z: (MH)- 351.2. Step 5: Benzyl (4'-(dimethylamino)-2',34',5!-tetrahydro-[1,Γ-biphenyl]-4-yl)carbamate (1-1-f) (10.0 mmol) was dissolved in methanol (20 mL), palladium on carbon (0.35 g) was added and the reaction mixture was stirred under hydrogen at room temperature for 16 hours. The reaction mixture was filtered and the filtrate was evaporated to dryness to obtain a crude product, the crude product was washed with ethyl acetate and filtered, and the filter cake was the target compound 4-(4-(dimethylamino)cyclohexyl ) aniline (l-1-g) (1.20 g, 55%) as a white solid. LC-MS: m / z: (MH)= 219.2. Step 6: 2-(1,1-Difluoroallyl)-1-(6-(2-hydroxypropan-2-yl)pyridín-2-yl)-6-((4-(4-methylpiperazin-1-yl)phenyl ) amino)-1,2-dihydro-3H-pyrazolo[3,4-D]pyrimidin-3-one (represented by the formula M-h) (150 mg, 0.42 mmol) was dissolved in toluene (20 mL), 3-ctorophenoxyformic acid (105 mg, 0.47 mmol) was added and the reaction mixture was stirred at room temperature for 0.5 hour, then the reaction mixture was evaporated to dryness, the obtained sulfoxide intermediate was dissolved in dimethyl sulfoxide (10 mL); 4-(4-methylpiperazin-1-yl)aniline (120 mg, 0.55 mmol) and trifluoroacetic acid (0.2 mL) were added and the reaction mixture was heated to 60 °C and stirred for 24 hours. . The pH value of the reaction mixture was adjusted to 9 with a saturated solution of sodium carbonate, water (50 mL) and dichloromethane (50 ml) were added, the phases were separated and the organic phase was washed with saline solution. saturated, dried over anhydrous sodium sulfate, filtered, evaporated to dryness, prepared and purified in liquid phase to obtain compound 1-1-1 and compound 1-1-2. Compound 1-1-1: HPLC retention time (RT) = 10.55 min (HPLC conditions: gradient elution, 5% mobile phase B —> 50% mobile phase B), the yield of the compound was 56% (110 mg) as a white solid.: 'H NMR (400 MHz, MeOD) δ 8.85 (s, 1 H), 8.46 (s, 2 H), 7.99 (t, J = 7.9 Hz, 1 H), 7.79 (d, J = 8.0 Hz, 1 H), 7.65 (dd, J = 16.6, 8.1 Hz, 3 H), 7.22 (d, J = 8.6 Hz, 2 H), 5.73 (ddt, J = 16.3, 10.2, 6.1 Hz, 1 H), 5.05 (dd, J = 10.3, 1.1 Hz, 1 H), 4.93 (dd, J = 17.1, 1.3 Hz, 1 H), 4.82 (d, J = 6.1 Hz, 2 H), 2.90 (s, 6 H), 2.60 (d, J = 8.4 Hz, 1 H), 2.21 (s, 2 H), 2.10 (d, J = 10.6 Hz, 2 H), 1.70 (d, J = 11.4 Hz, 4 H), 1.59 (s, 6 H).LC-MS : m / z: (MH)= 528.3. Compound 1-1-2: HPLC retention time (RT) = 10.78 min (HPLC conditions: gradient elution, 5% mobile phase B > 50% mobile phase B), the yield of the compound was 72% (160 mg) as a white solid: 'H NMR (400 MHz, CDCh) δ 8.86 (s, 1 H), 8.54 (s, 1 H), 7.95 (t, J = 7.9 Hz, 1 H), 7.75 (d, J = 8.0 Hz, 1 H), 7.59 (d, J = 8.5 Hz, 2 H), 7.43 (d, J = 7.6 Hz, 1 H), 7.32 (d ,J = 8.5 Hz, 2 H), 5.72 (ddt, J = 16.5, 10.3, 6.2 Hz, 1 H), 5.06 (d, J = 10.2 Hz, 1 H), 4.95 (dd, J=17.1, 1.0 Hz, 1 H), 4.75 (d, J = 6.1 Hz, 2 H), 3.05 (m, 1 H), 2.93 (m, 1 H), 2.68 (s, 6 H ), 2.32 (m. 2 H), 1.84 (m. 6 H), 1.60 (s, 6 H). LC-MS: m / z: (MH) - 528.3. Implementation 3: i-3-2 Compound (1-3-1) and compound (I-3-2) can be synthesized by the same method as in embodiment 1 using cyclopentane as raw material. The details were as follows: QQfrQ I η / 77Π7 / =1 / ΥΙΛ Sodium borohydride acetate (0.85 g, 4 mmol) was added to a mixture of tert (4'oxo-2',3',4',5'-tetrahydro-[1,T-biphenyl]-4-yl) butyl carbamate (0.46 g, 1.6 mmol) (l-8-c) and tetrahydropyrrole (0.28 g, 3.9 mmol) in 20 mL of dichloromethane and the mixture was stirred overnight at room temperature; The reaction mixture was washed with saturated aqueous sodium carbonate solution (20 mL), water (2x10 mL) and saturated saline solution sequentially; the organic phase was dried over anhydrous sodium sulfate and the residue was mixed with silica gel and passed through a column {7M ammoniacal methanol: (dichloromethane: ethyl acetate = 12: 2) = 0-15%} to obtain compound l-3-a, 200 mg of white solid. The yield was 40%. LC-MS: m / z: (Μ H) = 343. Step 2: Fert-butyl (4'-(pyrrolidin-1-yl)-2', 34', S'-tethiahydro-jlJ'-biphenii]-4-yl) carbamate (300 mg, 0.87 mmol) (l-3- a) and 10% palladium on carbon (100 mg) were added to 30 ml of methanol, the reaction flask was vented three times with a hydrogen balloon and the reaction mixture was stirred overnight at room temperature in an atmosphere of hydrogen. The reaction mixture was filtered and evaporated to dryness to obtain a crude product, which was separated by thin layer chromatography on a silica gel plate {methane! 7M ammoniacal: (dichloromethane: ethyl acetate = 9: 3) = 1:12} to obtain compound 1-3-2-b, 70 mg of white solid (Rf = 0.7) and compound 1-3-1-b , 90 mg of white solid (Rf = 0.5). Total performance! It was 52%. LC-MS: m / z: (MH) = 345. Step 3: Tert (4-(4-(pyrrolidin-1-ii)cyclohexyl)phenyl)butyl carbamate (l-3-2-b) (Rf = 0.7) (70 mg, 0.2 mmol) was added to 2 mL of dichloromethane, then 2 ml of trifluoroacetic acid were added and the mixture was stirred at room temperature for 2 hours. After the reaction mixture was concentrated, a brown oil (1-3-2-c) was obtained, which was directly used for the next step. LC-MS: m / z: (MH) = 245. Tert (4-(4-(pyrrolidin-1-ii)cyclohexyl)phenyl)butyl carbamate (1-3-1-b) (Rf = 0.5) (70 mg, 0.2 mmol) was added to 2 ml of dichloromethane, then 2 ml of tdfluoroacetic acid were added and the mixture was stirred at room temperature for 2 hours. After the reaction mixture was concentrated, a brown oil (1-3-1-c) was obtained, which was used directly for the next step. LC-MS: m / z: (MH) = 245. Stage 4: m-Chloroperoxybenzoic acid (66 mg, 0.326 mmol) was added to a solution of 2-allyl1-(6-(2-hydroxypropan-2-ii)pyridin-2-yl)-6-(methylthio)-1,2 -dihydro-3H-pyrazolo[3,4-D]pyrimidin-3-one (l-1-h) (90 mg, 0.25 mmol) in 10 mL of toluene and the mixture obtained was stirred at room temperature for 1 hour. The above reaction mixture was concentrated and then 4-(4-(azetidin-1-yl)cyclohexyl)aniline trifluoroacetate (1-3-1-c) (0.26 mmol), 0.15 mL of acid were added. trifluoroacetic acid and 3 ml of dimethyl sulfoxide and the mixture was stirred at 60 °C overnight. 2 mL of saturated aqueous sodium carbonate solution and 10 mL of water were added to the above reaction mixture, and the mixture was extracted three times with dichloromethane (3 x 10 mL); then, the organic phase was combined, washed with 5 mL of water and 5 mL of saturated sodium chloride solution, respectively, dried over anhydrous sodium sulfate, and concentrated to obtain a crude product; the crude product was separated by thin layer chromatography plate {7M ammoniacal methanol: (dichloromethane:ethyl acetate = 5:1) = 1:12} to obtain compound 1-3-1, 40 mg white solid ( Rf = 0.4), the yield was 28%. Compound 13-1: HPLC retention time (RT) = 11.01 min (HPLC conditions: mobile phase A was water (containing 0.1% HCOOH), mobile phase B was acetonitrile; gradient elution: 5 % mobile phase B 50% mobile phase B), Ή NMR (400 MHz, CDCh) δ 8.87 (s, 1 H), 7.90 (t, J = 7.9 Hz, 1 H), 7.78 (d, J = 8.0 Hz, 1 H), 7.53 (d, J = 8.5 Hz, 2 H), 7.39 (dd, J = 7.6, 0.5 Hz, 1 H), 7.20 (d, J = 8, 5 Hz, 2 H), 5.72 (ddt, J = 16.4, 10.2, 6.2 Hz, 1 H), 5.06 (dd, J = 10.2, 1.0 Hz, 1 H), 4.95 (dd, J = 17.1 , 1.2 Hz, 1 H), 4.76 (d, J = 6.2 Hz, 2 H), 4.04 (s, 1 H), 2.66 (m, 4 H), 2.58 - 2.47 (m , 1 H), 2.16 (m, 4 H), 1.96 (m, 2 H), 1.87- 1.78 (m, 4 H), 1.60 (s, 6 H), 1.58- 1.39 (m , 4H). CLEM: m / z: (MH) = 554. m-chloroperoxybenzoic acid (60 mg, 0.296 mmol) was added to a solution of 2-allyl-1(6-(2-hydroxypropan-2-yl)pyridin-2-íl)-6-(methylthio )-l ,2 -dihydro-3H-pyrazolo[3,4-D]pyrimidin-3-one (i-1-h) (80 mg, 0.22 mmol) in 10 mL of toluene and the mixture obtained was stirred at room temperature for 1 hour. The above reaction mixture was concentrated and then 4-(4-(azetidine-1-II)cyclohexyl)aniline trifluoroacetate (1-3-2-c) (0.2 mmol), 0.15 ml of acid were added. trifluoroacetic acid and 3 ml of dimethylsulfoxide and the mixture was stirred at 60 °C overnight. 2 mL of saturated aqueous sodium carbonate solution and 10 mL of water were added to the above reaction mixture, and the mixture was extracted three times with dichloromethane (3x10 mL); then the organic phase was combined, washed with 5 mL of water and 5 mL of saturated sodium chloride solution, respectively, dried over anhydrous sodium sulfate and concentrated to obtain a crude product; The crude product was separated by thin layer chromatography plate {7M ammoniacal methanol: (dichloromethane: ethyl acetate = 5: 1) = 1:12} to obtain compound 1-3-2, 50 mg white solid ( Rf = 0.6), the yield was 40%. Compound 13-2: HPLC retention time (RT) = 11.20 min (HPLC conditions: mobile phase A was water (containing 0.1% HCOOH), mobile phase B was acetonitrile; gradient elution : 5% mobile phase B 50% mobile phase B),1H NMR (400 MHz, CDCI3) δ 8.87 (s, 1 H), 7.92 (t, J - 7.9 Hz, 1 H), 7.80 (d, J = 8.0 Hz, 1 H), 7.52 (d, J = 8.5 Hz, 2 H), 7.38 (d, J = 7.6 Hz, 1 H), 7.29 (t, J = 4.2 Hz , 2H). 5.79-5.66 (m, 1 H), 5.06 (dd, J = 10.2, 1.0 Hz, 1 H), 4.96 (dd, J = 17.1, 1.2 Hz, H), 4.77 (d, J - 6.2 Hz, 2 H), 4.02 (s, 1 H), 2.70 - 2.50 (m, 5 H), 2.26 (s, 1 H), 1.98 ( m, 4H), 1.82 s, 4H), 1.69- 1.56 (m, 10H). LC-MS: m / z: (MH) = 554. Embodiment 4: 0. Λ ° ÍMO2 A. ¡I Ί Ύ Sr J-J-a ' ' .yA i Λ-H HN N N °'r 0 PdíPPM. L । L ¡i \ A A-n , γ.......T..............ay “·* o Ux0H ¡' ; Oiownc AQ 1)m-cpba Ύ' '''A ÍOWSSh l J ί J 2)O!P£A 1 Y T í Ί 0 0 ' <Y 0 A -0 ' Y M-b M-c M-d M Step 1: l-bromine ^-nitrobenzene (l-4-a) (692 mg, 3.43 mmol), 444.4.5>54ethΓamethyl·1.3i2” ethyl dioxaborolan-2-yl)cyclohex-3-ene-1-carboxylate (l-4-b) (800 mg, 2.85 mmol), tetrakis(triphenylphosphine)palladium (330 mg, 0.286 mmol), triphenylphosphine (75 mg, 0.286 mmol) and potassium carbonate (789 mg, 5.71 mmol) were dissolved in 1,4-dioxane (20 mL), the mixture was heated to 90 °C under the protection of argon and stirred for approximately 16 hours. Then, the reaction mixture was concentrated and purified by column chromatography (silica gel, petroleum ether / ethyl acetate = 100% to 90%) to obtain 450 mg of the compound represented by the formula, l-4-c like a white solid. Performance: 47%.1H NMR (400 MHz, CDCh) δ 8.23 - 8.16 (m, 2H), 7.57 - 7.49 (m, 2H), 6.33 (dd, J = 5.1, 2.8 Hz, 1H), 4.26 - 4.15 ( m, 2H), 2.72 - 2.61 (m, 1H), 2.59 - 2.51 (m, 4H), 2.24 (ddd, J = 9.3, 8.0, 3.9 Hz, 1H), 1.90 (dddd, 13.1, 11.0, 8.8 , 6.7 Hz, 1 H), 1.31 (dd, J - 9.2, 5.1 Hz, 3 H). Step 2: Ethyl 4-(4-nitrophenyl) cyclohex-3-ene-1-carboxylate (l-4-c) (450 mg, 1.63 mmol) was dissolved in methanol (10 mL), palladium / carbon catalyst was added ( 45 mg, 10%) and the mixture was stirred at room temperature for about 2 days under hydrogen atmosphere, filtered, the filtrate was concentrated and purified by column chromatography (silica gel, petroleum ether / ethyl acetate = 100% to 90%) to obtain 280 mg of the compound represented by the formula l-4-d as a white solid. Performance: 69%. LC-MS: m / z: (MH)=5248.4. Step 3: 2-aHk1 -[6-(1 -hydroxy-1 -methyl-ethyl)-2pyridyl]-6-methylthiopyrazolo[3,4-0]pyrimidin-3-one (I1-h) (428 mg, 1.20 mmol) was dissolved in toluene (20 mL), m-chloroperoxybenzoic acid (259 mg, 1.5 mmol) was added, the mixture was stirred at room temperature for about 1 hour, then 4-(4-aminophenyl)cyclohexane was added ethyl carboxylate (247 mg, 1.0 mmol) and DIPEA (258 mg, 2.0 mmol) and the mixture was heated to 90 °C and stirred for approximately 16 hours. The reaction mixture was concentrated and purified by column chromatography (silica gel, dichloromethane / methanol = 100% to 90%), high-performance preparative liquid phase and thin layer chromatography (DCM / CH3OH / NH3 CH3OH = 10 / 1 / 0.15) to obtain ^5 440 mg of the compound represented by formula I-4 as a white solid, yield: 79%. 1H NMR (400 MHz, CDCb) 5 8.87 (d, J = 2.1 Hz, 1 H), 7.91 (td, J = 7.9, 1.5 Hz, 1 H), 7.78 (d. J = 8.0 Hz, 1H), 7.54 (t, J = 7.9 Hz, 2H). 7.39 (d, J = 7.7 Hz, 1 H), 7.21 (d, J = 8.5 Hz, 2 H), 5.72 (ddt, J= 16.4, 10.2, 6.2 Hz, 1 H) , 5.07 (dd, J = 10.2, 1.1 Hz, 1 H), 4.96 (dd, J = 17.1, 1.2 Hz, 1 H), 4.77 (d, J= 6.2 Hz, 2H), 4.25 4.10 (m, 2H), 3.95 (s, 1H), 2.73 (s, 1H), 2.56 (dt, J = 15.5,2010.8 Hz, 1 H), 2.28 (d, J = 7.9 Hz, 1 H) , 2.14 (d, 10.6 Hz, 1 H), 2.05 -1.97 (m, 1 H), 1.78 (dd, J = 19.0, 8.5 Hz, 1 H), 1.67 (dt, J = 10,1,6.1 Hz, 3 H), 1.61 (s, 6 H), 1.59- 1.44 (m, 1 H), 1.34 1.26 (m, 3 H).LC-MS: m / z: (MH)= 557.4. Embodiment 5: 4-[4-[[2-Allyl-1-[6-(1-hydroxy-1-methyl-ethyl)-2pyridyl]-3-oxo-pyrazolo[3,4-D]pyrimidin-6-ethyl[ amino]phenyl]cyclohexane carboxylate (I-4) (420 mg, 0.75 mmol) was dissolved in methane! (20 mL), 2 N aqueous sodium hydroxide solution (10 mL) was added, the mixture was stirred at room temperature for about 3 days, concentrated to remove methanol, extracted with dichloromethane, then the layer was discarded. organic and the pH value was adjusted to 4 by adding 1 N aqueous hydrochloric acid solution to the aqueous layer, then the aqueous layer was extracted with dichloromethane; and the organic layer was dried over anhydrous sodium sulfate, concentrated, purified by column chromatography (silica gel, dichloromethane i methanol = 100% to 95%) to obtain 256 mg of the compound represented by formula I-5 as un5white solid, yield: 64%. NMR (400 MHz, MeOD) δ 8.84 (d, J- 1.4 Hz, 1 H), 8.00 (td, J = 7.9, 4.0 Hz, 1 H), 7.83 - 7.76 (m, 1 H), 7.67 (dd, J = 7.7, 0.7 Hz, 1 H), 7.60 (dd, J = 8.4, 5.7 Hz, 2H), 7.19 (dd, J = 13.2, 8.6 Hz, 2H), 5.73 (ddd, J = 17.0, 6.1,4.1 Hz, 1 H), 5.08-5.03 (m, 1 H), 4.95 (day, J = 1.3 Hz, 1 H), 4.86 - 4.79 (m, 2 H), 2.72 (s, 1 H), 2.58 (s, 1 H), 2.27 ( d, J = 6.7 Hz, 1 H), 2.13(d, J= 10.0 Hz, 1 H), 1.96 (d, J = 10.2 Hz, 1 H), 1.80- 1.66 (m, 4 H), 1.64- 1, 5210(m, 7 H).LC-MS: m / z: (MH)= 529.3. Embodiment 6 40 mg (0.076 mmol) of 4-(4-((2-allyl-1-(6-(2-hydroxypropan-2-¡l)pyridin-2-yl)3-oxo-2,3-d) were dissolved hydro-1H-pyrazolo [3,4-D] pyrimidin-6-yl) amino) phenyl) cyclohexane-1-carboxylic acid (1-5) in 5 mL of dichloromethane and 9 mg (0.11 mol ) of dimethylamine hydrochloride, 17 mg (0.11 mmol) of EDCI, 15 mg (0.11 mmol) of HOBt and 19 mg (0.15 mmol) of DIPEA, and the mixture was stirred at room temperature for approximately 16 hours, and then purified by thin layer chromatography (DCM / CH3OH ~ 100 / 10) to obtain 15 mg of a light yellow solid (I-δ), the yield was 35%.1H NMR (400 MHz, CDCI3) δ 8.86 (d, J = 4.2 Hz, 1 H), 7.97 - 7.88 (m, 1 H), 7.79 (d, J = 8.0 Hz, 1 H), 7.53 (dd, J = 12.3, 8 .5 Hz, 2H), 7.39 (d, J = 7.6 Hz, 1 H), 7.28 - 7.15 (m, 2 H), 5.80 - 5.65 (m, 1 H), 5.06 (d, J = 10.0 Hz, 1 H), 4.95 (d, J = 17.1 Hz, 1 H), 4.77 (d,J = 6.0 Hz, 2H), 3.10 (d, J = 12.1 Hz, 3 H), 2.98 (s, 3 H), 2.67 - 2.57 (m, 1 H), 2.14 (dd, J = 20.9, 10.3 Hz, 1 H), 2.06 - 1.97 (m, 2 H ), 1.92 (d, J = 14.0 Hz, 1 H), 1.78 1.66 (m,4H), 1.61 (s, 6 H), 1.49 (dd, J = 22.8, 12.2 Hz. 1H).LC-MS : m / z: (MH)= 556.3. Embodiment 7 Μ QQfrQ Ln / ZZnZ / q / YIA 40 mg (0.076 mmol) of 4-(4-((2-allyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)3-oxo-2,3-dihi) were dissolved dro-1H-pyrazolo [3,4-D] pyrimidin-6-yl) amino) phenyl) cidohexane-1-carboxylic acid (I-5) in 5 mL of dichloromethane and 9 mg (0.11 mol) of hydrochloride azetidine (l-7-a), 17 mg (0.11 mmol) of EDCI, 15 mg (0.11 mmol) of HOBt and 19 mg (0.15 mmol) of DIPEA were added, and the mixture was stirred at room temperature for about 16 hours and then purified by thin layer chromatography (DCM / CH3OH = 100 / 10) to obtain 15 mg of light yellow solid (1-7), the yield was 35%. Ή NMR (400 MHz, CDCh) δ 8.85 (d, J4.7 Hz, 1 H), 7.91 (dt, 10.7,7.9 Hz, 1 H), 7.78 (d, J=7.8 Hz, 1 H), 7, 53 (dd,J= 12.0, 8.5 Hz, 2H). 7.39 (dd, J = 7 6. 2.4 Hz, 1 H), 7.22 (dd, 19.5,8.5 Hz, 2H), 5.71 (ddt,J= 16.4, 10.2,6.2 Hz, 1 H), 5.06 (d, 10.2 Hz, 1 H), 4.95 (d, J = 17.1 Hz, 1 H), 4.77 (d, J = 6.1 Hz, 2 H), 4.21 ( dd, J = 16.4, 8.6 Hz, 2H), 4.10 - 4.02 (m, 2H), 2.63 - 2.52 (m, 2H), 2.35 - 2.20 (m, 2H), 2.15 2.07 (m, 1H), 2.00 (dd , 13.4, 3.0 Hz, 2 H), 1.92- 1.83 (m, 1 H), 1.79- 1.63 (m, 4 H), 1.60 (s, 6 H), 1.48 (ddd, J = 24.7, 12.5, 2.5 Hz, 1H).LC-MS: m / z: (MH)= 568.4. Embodiment 8 Step 1; QQfrQ Ln / 77n7 / q / YIA 4.4.5,5-tetramethyl-2-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-1,3,2-dioxaborolane (1-1-c) (19 g, 71.4 mmol ), tert-butyl (4-bromophenyl) carbamate (l-8-a) (18.4 g, 67.6 mmol), aqueous sodium carbonate solution 2 mo! / L (75 mL) and Pd(dppf)Ch ( 3.3 g, 4.5 mmo!) was added to 250 ml of 1,4-dioxane and the reaction flask was vented with a nitrogen balloon three times and the mixture was stirred at 98°C overnight. The reaction mixture was filtered and concentrated, and the aqueous phase was extracted with ethyl acetate (2 x 100 mL), the combined organic phase was washed with saturated saline, dried over anhydrous sodium sulfate and concentrated to obtain a crude product, which was purified by column (ethyl acetate: petroleum ether = 0-40%) to obtain 19 g of a brown solid (l-8-b). The performance was 84.8%. LC-MS: m / z: (Μ-56+Hf = 276. Step 2: 1.38 mol / l hydrochloric acid (160 ml) was added to a solution of phero-butyl (4-(1,4dioxaspira[4.5]dec-7-en-8-yl)phenyl)carbamate (l-8-b ) (16 g, 48 mmol) in 100 ml of tetrahydrofuran and the mixture was stirred at room temperature overnight. Then, the mixture was extracted with ethyl acetate (2 x 150 mL), the combined organic phase was washed three times with saturated saline, and the organic phase was dried over anhydrous sodium sulfate and concentrated to obtain 13.5 g of a yellow-brown solid (l-8-c), which was used directly for the next step. The performance was 97%. LC-MS: m / z: (M-56+H)+= 232. Step 3: Λ / ,Λ / '-diisopropylethylamine (12 mL, 69 mmol) and sodium borohydride acetate (14 g, 71 mmol) were added to a mixture of ten-butyl (4'-oxo-2\3',4\ 5'-tetrahydro-[1,r-biphenyl]-4yl)carbamate (i-8-c) (10 g, 34.8 mmol) and azetidine hydrochloride (3 g, 32 mmol) in 100 ml of dichloromethane and the mixture was stirred at room temperature overnight; then the solvent was evaporated and 100 ml of dichloromethane was added and the mixture was washed with saturated aqueous sodium carbonate solution (20 ml), water sequentially; then the organic phase was dried, mixed with silica gel and passed through (2 ammoniacal 7M: (dichloromethane: ethyl acetate ~ 15:1) = 0-15%} to obtain 7.3 g of white solid (l-8-d). The performance was 64%. LC-MS: m / z; (M+H)+= 329. Step 4: Terf-butyl (4'-(azetidin-1-yl)-2,,3',4',5'-tetrahydro-[1,T-biphenyl]-4-¡l)carbamate (l-8-d) (7.3 g, 22 mmol) and 10% palladium on carbon (200 mg) to 150 ml of methanol, the reaction flask was vented three times with a hydrogen balloon and the reaction mixture was stirred overnight at room temperature in an atmosphere. The reaction mixture was filtered and evaporated to dryness to obtain a crude product, the crude product was washed with ethyl acetate and filtered, and the filter cake was 4.1 g of compound, l-8-e (Rf = 0.4) as a white solid. The total yield was 85%. LC-MS: m / z: (M+H)+= 331. Step 5: Tero-butyl (4-(4-(azetidin-1-yl)cyclohexyl)phenyl)carbamate (3 g, 9 mmol) (represented by the formula ί-8-e) to 20 ml of dichloromethane, then 20 were added ml of trifluoraacetic acid and the mixture was stirred at room temperature for 2 hours. After concentrating the reaction mixture, 10 ml of water and 20 ml of saturated sodium carbonate solution were added, and the solid formed was filtered, washed with water and drained to obtain 1.8 g of compound. I8-f as a brown solid, which was used directly in the next step. The yield was 86%.1H NMR (400 MHz, CDCI3) δ 7.08 - 6.96 (m, 2H), 6.70 - 6.60 (m, 2H), 3.57 (s, 2H), 3.22 (t, J = 7.0 Hz, 4H), 2.38 (ti, J = 12.1,3.2 Hz, 1H), 2.15 - 1.95 (m, 5H), 1.95-1.81 (m, 4H), 1.51 1.30 (m, 2H), 1.21 - 1.04 (m, 2H).LC- MS: m / z: (M+H)+= 231. Step 6: m-chloroperaxybenzoic acid (1.33 g, 6.57 mmol) was added to a solution of 2-alll-l (6-(2-hydroxypropan-2-yl)pyridin-2-íl)-6-(methylthio )-1,2-dihydro-3H-pyrazolo[3,4-D]pyrimidin-3-one (1.86 g, 5.2 mmol) (represented by l-1-h) in 60 mL of toluene, and The mixture obtained was stirred at room temperature for 1 hour. The above reaction mixture was concentrated and then 4-(4-(azetidin-1-yl) cyclohexyl)aniline (1.2 g, 5.2 mmol) (represented by l-8-f), 0.8 ml was added. of trifluoroacetic acid and 20 ml of dimethyl sulfoxide and the mixture was stirred at 60°C overnight. 20 ml of saturated aqueous sodium carbonate solution and 50 ml of water were added to the above reaction mixture, and the mixture was extracted three times with dichloromethane (3 x 150 ml); then the organic phase was combined, washed with 50 mL of water and 30 mL of saturated sodium chloride solution, respectively, dried over anhydrous sodium sulfate and concentrated to obtain a crude product; The crude product was separated by a thin layer chromatography plate {7M ammoniacal methanol: (dichloromethane: ethyl acetate = 5:1) = 1:12} to obtain compound I-8, 1.88 g of a white solid, the performance was 67%.1H NMR (400 MHz, CDCI3) δ 8.86 (s, 1 H), 7.93 - 7.85 (m, 1 H), 7.78 (d, J = 7.8 Hz, 1 H), 7.52 ( d, J = 8.5 Hz, 2 H), 7.39 (dd, J = 7.6, 0.7 Hz, 1 H), 7.19 (d, J = 8.5 Hz, 2 H), 5.71 (ddt , J = 16.4, 10.2, 56.2 Hz, 1 H), 5.05 (dd, J = 10.2, 1.1 Hz, 1 H), 4.94 ( dd, J - 17.1, 1.3 Hz, 1 H ), 4.77 (d, J = 6.2 Hz, 2 H), 4.11 (d, J = 8.9 Hz, 1 H), 3.24 (t, J = 7.0 Hz, 4 H), 2.52 - 2.43 (m, 1 H), 2.14 - 2.00 (m, 3H), 1.92 (d,J = 11.2 Hz,4H), 1.60 (s, 6 H), 1.45(dt, J = 14.9, 7.5 Hz, 2 H ), 1.23- 1.08 (m, 2 H). LC-MS: m / z: (Μ+Η)+= 540.4. Embodiment 8-1 θ The product of embodiment 8 (compound I-8) was detected by HPLC (conditions: mobile phase A was water (containing 0.1% HCOOH), mobile phase B was acetonitrile; gradient elution: 5% mobile phase B —► 50% mobile phase B) with the only retention time: HPLC retention time (RT) = 10.78 min. Therefore, its cyclohexyl part was cis or trans, that is 0 / — 10 hn'S- N Á J~N □ ; OH N (-8-1 i.e. was V , J refers to cis 0 trans. 20 The reaction route was as follows: θΩθ I V” χ Λ 0 ó ó τ I JL i—i HCI : soo-·!H ,,χ ------------*- ιίη 1 b -a : k zj o' '0 ---------» γ.^-1 χγ ----- -----*· y j 25 H-C Bqcz^í l-8-b Bo / H 1-8-C J !-8d 'Boc 0 0 n Z\ y- ^ΥΛ· / jj 1 -N ll zL X- 'Xr'x riz Realization 8-2 2-al¡l-1-(6-(2-hydroxypropan)pyridin-2-¡l)-6-((4-(4-oxocyclohexyl)pheny¡)amino)-1,2-dihydro3H-pyrazolo[3 ,4-D]pyrimidin-3-one (1-19-d) (19.0 mmol) was dissolved in dichloromethane (500 ml) and azetidine hydrochloride (21.0 mmol), / V-ethyl-A / -isopropyl- was added 2-amine (38.0 mmol) and sodium triacetoxyborohydride (57 mmol) to the reaction mixture and the reaction mixture was stirred at 30°C for 16 hours. Water (300 ml) and potassium carbonate were added to the reaction mixture, the pH value was adjusted to 9 and the mixture was extracted with dichloromethane; The organic phase was washed with saturated saline, dried over anhydrous magnesium sulfate, filtered, and the filtrate was evaporated to dryness to obtain a crude product, and the crude product was purified by column chromatography (dichloromethane / methanol = 0 / 100-5 / 95) to obtain Ί5 target compound 1-8-1 (1.8 g, 24.7%) and target compound I-8-2 (4.7 g, 65.3%), both being white solids. Compound 1-8-1: HPLC: retention time (RT) = 10.78 min (HPLC conditions: mobile phase A was water (containing 0.1% HCOOH), mobile phase B was acetonitrile; gradient elution: 5% mobile phase B — 50% mobile phase B),1H NMR (400 MHz, CDCh) δ 8.86 (s, 1 H), 20 7.93 - 7.85 (m, 1 H), 7.78 (d, J = 7.8 Hz, 1H), 7.52 (d, J = 8.5 Hz, 2H), 7.39 (dd, J = 7.6, 0.7 Hz, H), 7.19 (d, J = 8.5 Hz, 2 H), 5.71 (ddt, J = 16.4, 10.2,6.2 Hz, 1 H), 5.05 (dd, J = 10.2, 1.1 Hz, 1H), 4.94 (dd, J = 17.1, 1.3 Hz, 1H), 4.77 (d, J = 6.2 Hz,2H), 4.11 (d, J = 8.9 Hz, 1 H), 3.24 (t, J = 7.0 Hz, 4 H), 2.52-2.43 (m, 1 H), 2.14-2.00 (m, 3 H), 1.92 (d, J = 11.2 Hz, 4 H), 1.60 (s, 6 H), 1.45 (dt, J = 14.9, 7.5 Hz, 2 H), 1.23- 1.08 (m, 2 H). LC-MS: m / z: (M+H)+= 540.4. Compound I-8-2: HPLC: retention time (RT) = 11.00 min (HPLC conditions: mobile phase A was water (containing 0.1% HCOOH), mobile phase B was acetonitrile; gradient elution: 5% mobile phase B 50% mobile phase B),1H NMR (400 MHz, CDCI3) δ8.87 (s, 1 H), 7.92 (d, J = 7.8 Hz, 1 H), 7.80 (d , J = 8.0 Hz, 1 H), 7.52 (d, J = 8.4 Hz, 2 H), 7.39 (d, J = 7.6 Hz, 1 H), 7.29 - 7.25 ( m, 2 H), 5.82-5.63 (m, 1 H), 5.12-4.91 (m, 2 H), 4.78 (d, J = 6.2 Hz, 2 H), 4.01 (S, 1 H) , 3.17 (s, 4 H), 2.53 (s, 1 H), 2.33 (s, 1 H), 2.06 (d, J = 4.4 Hz, 2 H), 1.89 (d, J = 11.6 Hz, 2 H), 1.75 (d, J = 14.1 Hz, 2 H), 1.59 (d, J = 17.2 Hz, 8 H), 1.46 (t, J = 13 ,1Hz, 2H). LC-MS: 540.0 [M+1f. It can be seen that there was a large difference between the c / s- and freos-configuration hydrogen spectrum data, which was enough to distinguish them. QQfrQ Ln / 77n7 / q / YIA Realization 8-3 Step 1: Terf-butyl (4'-(a2etidin-1-yl)-2',3',4',5'-tetrahydro-[1,T-biphenyl]-4-yl)carbamate (l-8-d) ( 7.3 g, 22 mmol) and 10% palladium on carbon (200 mg) were added to 150 ml of methane, the reaction flask was vented three times with a hydrogen balloon, and the reaction mixture was stirred during the reaction. overnight at room temperature in a hydrogen atmosphere. The reaction mixture was filtered and evaporated to dryness to obtain a crude product, which was mixed with silica gel and passed through the column {7 M ammonia methane!: (dichloromethane: ethyl acetate = 12:3) = 0-15%} to obtain 2.1 g of compound l-8-e (Rf = 0.6) as a white solid and 4.1 g of compound !-8-e' as a white solid (Rf = 0.4) . Total performance! it was of! 85%. LC-MS: m / z: (M+H)+= 331. Step 2: Te / f-butyl (4-(4-(azetidin-1-yl)cyclohexyl)phenyl)carbamate (2 g, 9 mmoi) (represented by the formula !-8-e'j was added to 20 ml of dichloromethane, then 20 ml of trifluoroacetic acid were added and the mixture was stirred at room temperature for 2 hours. After concentrating the reaction mixture, 10 ml of water and 20 ml of saturated sodium carbonate solution were added, and The formed solid was filtered, washed with water and drained to obtain 1.2 g of compound, l-8-f" as a brown solid, which was used directly in the next step. The yield was 86%.1H NMR (400 MHz, MeOD) δ 7.10 - 6.97 (m, 2H), 6.74 - 6.63 (m, 2H), 4.22 - 4.08 (t, J = 8.0 Hz, 4H), 3.47 - 3, 38 (m, 1H), 2.61 - 2.52 (m, 1H), 2.52 - 2.28 (m, 2H), 1.92 - 1.62 (m, 8H). : (M+H)* = 231. Step 3: m-Chloroperoxybenzoic acid (1.33 g, 6.57 mmol) was added to a solution of 2-allyl-1(6-(2-hydroxyprapan-2-yl)pyridin-2-yl)-6-(methylthio) -1,2-dihydro-3H-pyrazolo[3,4-D]pyrimidin-3-one (1.86 g, 5.2 mmol) (represented by 1-1 -h) in 60 ml of toluene and the mixture obtained was stirred at room temperature for 1 hour. The above reaction mixture was concentrated and then 4-(4-(azetidin-1 -i!) cyclohexyl)aniline (1.2 g, 5.2 mmol) (represented by l-8-f j) was added. 0.8 ml of trifluoroacetic acid and 20 ml of dimethylsulphoxide and the mixture was stirred at 60° C. overnight. 20 ml of saturated aqueous sodium carbonate solution and 50 ml of water were added to the above reaction mixture, and The mixture was extracted three times with dichloromethane (3 x 150 ml); then the organic phase was combined, washed with 50 mL of water and 30 mL of saturated sodium chloride solution, respectively, dried over anhydrous sodium sulfate and concentrated to obtain a crude product; the crude product was separated by thin layer chromatography plate {7M ammoniacal methanol: (dichloromethane: ethyl acetate = 5: 1) = 1:12} to obtain compound 1-8 -2, 1.88 g of a white solid, the yield was 67%. Ή NMR (400 MHz, CDCI3) 68.87 (s, 1 H), 7.92 (d, J = 7.8 Hz, 1 H), 7.80 (d, J = 8.0 Hz, 1 H),107.52 (d, J = 8.4 Hz, 2 H), 7.39 (d, J = 7.6 Hz, 1 H), 7.29 - 7.25 (m , 2H), 5.82 - 5.63 (m, 1H), 5.12 - 4.91 (m, 2 H), 4.78 (d, J = 6.2 Hz, 2 H), 4.01 (s, 1 H), 3.17 (s, 4 H), 2.53 (s, 1 H ), 2.33 (s, 1 H), 2.06 (d, J = 4.4 Hz, 2 H), 1.89 (d, J = 11.6 Hz, 2 H), 1.75 (d, J = 14.1 Hz , 2 H), 1.59 (d,J= 17.2 Hz, 8 H), 1.46 (t, J = 13.1 Hz, 2 H). LC-MS: m / z: (M+Hf = 540. Step 1: g (4.22 mmol) of 2.6-dibramopyridine (1-15-a) was dissolved in 30 ml of dichloromethane, the mixture was cooled to -780 C and 1.86 ml (4.64 mmol, 2 M dioxane solution) was added slowly dropwise. drop of a solution of n-butyllithium, after stirring the mixture for about 15 min, and 0.3 g (4.22 mmol) of oxetan-3-one (represented by formula I15-b) was added At the same time, stirring was continued for approximately 1 hour; and the mixture was quenched with saturated aqueous ammonium chloride solution and then extracted with dichloromethane, the organic layer was dried over anhydrous sodium sulfate, concentrated and purified by column chromatography (petroleum ether / ethyl acetate = 100% to 50%) to obtain 660 mg of 3-(6-bromo-2-pyridyl) oxetan-3-ol (1-15-c) as a white solid, the yield was 68%. LC-MS: m / z: (M+H)+= 230.1. Step 2: 106 mg (0.48 mmol) of 2-allyl-6-methylthiO-1H-pyrazolo[3,4-D]pyrimidin-3-one (l-15-d) and 100 mg (0.43 mmol) of 3 -(6-bromo-2-pyridyl)oxetan-3-ol (1-15-c) were dissolved in 10 ml of 1,4dioxane and then 90 mg (0.65 mmol) of potassium carbonate, 83 mg (0.43 mmol) of cuprous iodide and 77 mg (0.87 mmol) of ΝΊ,Ν 2-dimethylethyl-1,2-diamine was added and the mixture was heated to 100°C under the protection of argon and stirred overnight. . The residue was concentrated and purified by silica gel column chromatography (UV, dichloromethane / methanol = 100% to 10%) to obtain 140 mg of 2-ai¡l-1-[6-(3-hydroxyoxetan-3 -í!)-2-pyr¡d¡nyl]-6methylthiopyrazolo[3,4-D] pyrimidin-3-one (1-15-e) as a brown oil, the yield was 1086%. LC-MS: m / z: (M+H)+= 372.1. Step 3: 549 mg (1.478 mmol) 2-a!H-1 -[6-(3-hydraxioxetan-3-yl)-2-pyridinyl]-6-methylthiopyrazoium[3,4-d]pyrimidin-3-one (represented by 1-15-e) was dissolved in 30 ml of toluene, 397 mg (1.7714 mmol) of 3-chloroperoxybenzoic acid was added and the mixture was stirred at room temperature ^5 for approximately 1 hour, then 354 mg (1.622 mmol ) of 4-(4-(dimethylamino) cidohexH)aniline (1-1-f) and 381 mg (2.9480 mmol) of DIPEA were added and the reaction mixture was concentrated and purified by thin layer chromatography (dichloromethane / methanol / methanolic ammonia solution = 25 / 1 / 0.15) to obtain compound 1-15-1 and compound 1-15-2. Compound 1-15-1: HPLC retention time (RT) =207.02 min (HPLC conditions: gradient elution, 5% mobile phase B -> 95% mobile phase B), the yield of the compound was 10% (80 mg) as a white solid; 1H NMR (400 MHz, MeOD) δ 8.84 (s, 1 H), 8.04 (t, J = 7.9 Hz, 1 H), 7.92 (d, J = 8.1 Hz, 1 H). 7.67 (d, J = 7.6 Hz, 1 H), 7.60 (d, J = 8.6 Hz, 2 H), 7.21 (d, J = 8.6 Hz, 2 H), 5.78 (ddt, 16.3, 10.3, 6 ,1 Hz, 1 H), 5.12-5.05 (m, 3 H), 4.98 (dd, J = 17.1, 1.3 Hz, 1 H), 4.89 (d, 0=6.1 Hz, 2 H), 4.84 (s, 2 H),253.68 (s, 2 H), 2.97 - 2.86 (m, 1 H), 2.66 (s, 6 H), 2.60 - 2.50 (m, 1 H), 2.15 (d. J = 8.6 Hz, 2 H), .04 (d, 0 = 9.0 Hz, 2 H), 1.66 - 1.54 (m, 4 H).LC-MS: m / z: ( M+H)-= 542.4. Compound 1-15-2: HPLC retention time (RT) = 7.16 min (HPLC conditions: gradient elution, 5% mobile phase B -> 95% mobile phase B), the yield of the compound was 20% (160 mg) as a white solid: 1H NMR (400 MHz, MeOD) δ 8.83 (s, 1 H), 8.04 (t, J = 7.9 Hz, 1 H), 7.9230(d, J = 8.0 Hz , 1 H), 7.67 - 7.62 (m, 1 H), 7.59 (d, J = 8.6 Hz, 2 H), 7.29 (d, J = 8.5 Hz, 2 H), 5.76 (ddt , J = 16.3, 10.2, 6.1 Hz, 1 H), 5.10-5.02 (m, 3 H), 4.96 (dd, J = 17.1, 1.3 Hz, 1 H), 4.87 (d , J = 6.8 Hz, 2 H), 4.82 (d, J = 6.8 Hz, 2 H), 2.73 (d, J = 4.2 Hz, 1 H), 2.29 (d, J = 21.9 Hz, 7 H), 2.04 - 1.90 (m, 4 H), 1.66 (dd, J = 15.6, 6.1 Hz, 4 H). LC-MS: m / z: (M+H)+= 542.3. QQfrQ I 0 / 7707 / 3 / ΥΙΛ Realization 19 EITHER Step 1: 4.4.5,5-tetramethyl-2-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-1,3,2-dioxaborolane (0.8 g, 3 mmol) (represented by formula 1 -1-c), 1-bromo-4-nitrobenzene (0.606 g, 3 mmol) (l-4-a), 1 mol / L aqueous sodium carbonate solution (6 mL) and Pd (PPhs^Ck (106 mg, 0.15 mmol) were added to 30 ml of 1,4-dioxane and the reaction flask was vented three times with a nitrogen balloon and the mixture was stirred at 95° C. overnight. filtered and concentrated, and the aqueous phase was extracted with ethyl acetate (2 x 30 mL), the combined organic phase was washed with saturated saline, dried over anhydrous sodium sulfate and concentrated to obtain a crude product, which was purified by column (ethyl acetate: petroleum ether = 0-30%) to obtain 0.73 g of 8-(4-nitrophenyl)-1,4-dioxaspiro[4.5]dec-7-ene (1-19-a) as a brown solid, the yield was 90%.1H NMR (400 MHz, CDCI3) δ 8.24 - 8.14 (m, 2 H), 7.60 - 7.50 (m, 2 H), 6.21 (td, J = 4.0, 2.0 Hz, 1 H), 4.06 (s, 4 H), 2.71 ( ddd, J = 6.5, 4.2, 1.7 Hz. 2 H), 2.59 - 2.49 (m, 2 H), 1.97 (t, J = 6.5 Hz, 2 H). LC-MS: m / z: (M+H)+= 262.3. Step 2: 8-(4-nitrophenyl)-1,4-dioxaspira[4.5jdec-7-ene (l-19-a) and 10% palladium on carbon (100 mg) to 50 ml of dichloromephane, the reaction flask was vented three times with a hydrogen balloon and the reaction mixture was stirred at room temperature for 4 hours in a hydrogen atmosphere. The reaction mixture was filtered and evaporated to dryness to obtain 560 mg of 4-(1,4-dioxaspiro[4.5]decan-8-yl)aniline (l-19-b) as a brown solid, which was used directly In the next step, the performance was 96%. LC-MS: m / z: (M+H)+= 234.3. Step 3: m-chloroperoxybenzoic acid (55 mg, 0.246 mmol) was added to a solution of 2-aliM (6-(2-hydroxypropan-2-yl)pyridin-2-yl)-6-(methylthio)-1,2 -dihydro-3H-pyrazolo [3,4-0] pyrimidin-3-one (72 mg, 0.2 mmol) (l-1-h) in 15 mL of toluene, and the mixture obtained was stirred at room temperature for 1 hour. The above reaction mixture was concentrated, and then 4(1,4-dioxaspiro[4.5]decan-8-yl)aniline (l-19-b) was concentrated, 0.15 ml of trifluoroacetic acid and 3 ml were added. of dimethyl sulfoxide and the mixture was stirred at 60°C overnight. 10 ml of saturated aqueous sodium carbonate solution and 25 ml of water were added to the above reaction mixture and the mixture was extracted three times with dichloromethane (3 x 20 ml); then the organic phase was combined, washed with 10 mL of water and 10 mL of saturated sodium chloride solution, respectively, dried over anhydrous sodium sulfate and concentrated to obtain a crude product; The crude product was separated by thin layer chromatography plate {7M ammoniacal mephanol: (dichloromethane: ethyl acetate = 5: 1) = 1:12} to obtain 60 mg of 6-((4-(1,4- dioxaspiro [4.5]decan-8-yl)phenyl)amino)-2-allyl-1-(6-(2-hydroxylpropan-2-yl)pyridin-2-yl)1,2-dihydro-3H-pyrazolo [3 ,4-0] pyrimidin-3-one (represented by l-19-c) as a white solid, the yield was 54%. LC-MS: m / z: (M+H)+= 543.3. Step 4: -((4-(1,4-dioxaspiro[4.5]decan-8-yl)phenyl)amino)-2-allyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)- 1,2-dihydro-3H-pyrazoium[3,4-D]pyrimidin-3-one (represented by 1-19-c) to a mixed solution consisting of 3 ml of tetrahydrofuran and 3 ml of hydrochloric acid 2 mol / L, and the mixture was stirred at room temperature overnight. The pH of the reaction mixture was adjusted to approximately 10 with sodium bicarbonate, extracted with dichloromethane (2 x 20 ml) and the crude product was concentrated after drying the organic phase over anhydrous sodium sulfate. The crude product obtained was separated by thin layer chromatography plate with methanol: (dichloromethane: ethyl acetate = 9: 3) = 1:12 to obtain 50 mg of 2-allyl-1 (6-(2-h¡ droxypropan-2-yl))pyridin-2-yl)-6-((4-(4-oxoc¡clohexyl)phenyl)am¡no)-1,2-dih!dro-3H-pyrazolo [3,4- d]pyrimidin-3-one (i-19-d) as a white solid, the yield was 90%. LC-MS: m / z: (M+H)1· = 499.3. Step 5: 2-ali!-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-6-((4-(4-oxoc¡clohexí)phenyl)amino)-1,2dihydro- 3H-pyrazolo[3,4-d]pyrimidin-3-one (50 mg, 0.1 mmol) (1-19-d) and ammonium acetate (77 mg, 1 mmol) to 10 ml of methanol, the mixture It was stirred at room temperature for 10 min, then sodium cyanoborohydride (30 mg, 0.5 mmol) was added and the mixture was stirred overnight at room temperature. After concentrating the reaction mixture, 1 ml of dichloromethane was added and the mixture was washed with 10 ml of 1 mol / L sodium carbonate solution and 5 ml of water sequentially. The organic phase was dried over anhydrous sodium sulfate and the crude product obtained was concentrated and used directly in the next step. 40 mg of white solid (1-19-e), the yield was 80%. LC-MS: m / z: (M+H)+= 500.3. Step 6: 2-ahi-6-((4-(4-aminocyclohexyl)phenyl)ammo)-1-(6-(2-hydroxy!prapan-2-yl)pindm-2-ii)-1,2dihydro-3H-pyrazolo [3,4-cfl pyrimidin-3-one (35 mg, 0.07 mmoi) (1-19-e) and N,Ndiisopropylethylamine (0.02 ml) was added to 10 ml of dichloromethane, then methanesulfonyl chloride (9 mg was added , 0.078 mmol) and the mixture was stirred overnight at room temperature. The reaction mixture was concentrated and then prepared by high-performance liquid phase to obtain 9 mg of Λ / -(4-(4 -((2-allyl-1-(6-(2-hydroxypropan-2-yl) pyridin-2-yl)-3-oxo2,3-dihydro-1H-p!razo¡o[3,4-d]pyrimidin-6-yl)amino)phenyl)cyc¡ohexyl)methanesulfonamide (1-19) as a white solid, the yield was 22%. 'H NMR (400 MHz, CDCh) δ 8.88 (s, 1 H), 7.91 (t, J = 7.9 Hz, 1 H), 7.77 (d, J = 7.9 Hz, 1 H), 7.56 (d, J = 8.5 Hz, 2 H), 7.40 (d, J = 7.4 Hz, 1 H), 7.19 (d, J = 8.5 Hz, 2 H), 5.78 - 5.66 (m , 1 H), 5.07 (dd, J = 10.2, 1.0 Hz, 1 H), 4.96 (dd, J = 17.1, 1.2 Hz, 1 H), 4.77 (d, J = 6.2 Hz, 2 H), 4.42 (d. J = 7.6 Hz, 1 H), 3.49-3.35 (m, 1 H), 3.04 (s, 3 H), 2.57 -2.46 (m, 1H), 2.29-2.17 (m, 2H), 2.05- 1.96 (m, 8H), 1.56-1.65 (m, 2H), 1,411.50 (m, 2H). LC-MS: m / z: (M+H)*= 578.3. Realization 20 nh2 2-al¡l·6-((4-(4-aminocyclohexyl)phenyl)amino)-1-(6-(2-hydroxyproρan-2-yl)pyridin-2-yl)-1,2dihydro-3H-pyrazolo [3,4-D]pyrimidin-3-one (120 mg, 0.24 mmol) (compound represented by I19-c), pyrazole-carboximidamide 1H-hydrochloride (45 mg, 0.31 mmol) and M , / V-diisopropylethylamine (0.2 ml) to 5 ml of N,^dimethylformamide, the mixture was stirred at 65°C overnight. The reaction mixture was concentrated and separated by thin layer chromatography plate (7 M ammoniacal methane: dichloromethane = 1:8) to obtain 30 mg of a white solid (compound represented by I-20), the yield was of 23%. LC-MS: m / z: (M+H)+= 542. 'H NMR (400 MHz, MeOD) δ 8.84 (s, 1 H), 8.02 (m, 1 H), 7.80 (m, 1 H) , 7.72-7.58 (m, 3 H), 7.25 (m, 2 H), 5.73 (ddt, J = 16.5, 10.3, 6.1 Hz, 1 H), 5.05 (dd, J = 10.2, 1.0 Hz, 1 H), 4.95 (d, 1 H), 4.83 (d, J = 6.1 Hz, 2 H), 3.54-3.42 (m , 1 H), 2.59 (m, 1 H), 2.14 (m, 1 H), 1.98 (m, 2 H), 1.83 (m, 1 Η), 1.68 (m, 2 Η), 1.60 (s, 6 Η), 1.50 ( m, 2H). Realization 23 ΊΛ / t / ZUZZ / U I0400 Potassium fert-butoxide (2 equiv, 0.2006 mmol) was dissolved in dry dimethyl sulfoxide (1 ml, 100% by mass), and then a solution of tosylmethyl isocyanide (1.5 equiv., 0.1504 mmol) in dry dimethyl sulfoxide (1 ml) was added thereto at room temperature. Compound (I-I9-d) (50 mg, 0.1003 mmol) was dissolved in dry methanol (0.5 ml), the solution was added to the above reaction mixture and then the reaction was stirred at room temperature for 12 hours. The reaction was quenched with water and extracted with ethyl acetate (2 x 20 ml), the organic phase was washed with saline solution (1 x 20 ml), dried over Na2SO4, filtered and concentrated to obtain a crude product. The crude product was refined by a normal phase silica gel column (elution conditions: dichloromethane / methanol system, methanol concentration 0% to 10%, 12 column volumes) to obtain compound (1-23): (15 mg, 0.02943 mmol), yield was 29.35%, yellow solid.1H NMR (400 MHz, DIVISO) δ 10.28 (s, 1 H), 8.88 (d, J = 1.8 Hz, 1 H ), 8.09 - 7.97 (m, 1 H), 7.75 (d, J = 8.4 Hz, 1 H), 7.66 (dd, J = 20.6, 8.5 Hz, 3 H), 7.19 (dd, J = 11,1,8.7 Hz, 2 H), 5.74-5.61 (m, 1 H), 5.00 (d, J = 10.2 Hz, 1 H), 4.82 (d, J = 17.1 Hz, 1 H), 4.69 (d, J = 5.5 Hz, 2 H), 3.23 (s, 1 H), 2.74 (t, J = 12.1 Hz, 1 H), 2.53 (s, 1 H), 2.12 (re, J= 10.1 Hz, 1 H), 1.98 (re, J = 13.2 Hz, 1 H), 1.82 (re, J = 13.2 Hz, 2 H), 1.77-1.57 (m, 3H), 1.49 (d, J = 18.2 Hz, 6H). LC-MS: m / z: (M+Hf= 510.2. Realization 31 QQfrQ I η / 77Π7 / =1 / ΥΙΛ Step 1: 3-(4-bromophenyl) cyclobutanone (!-31-a) (4.40 mmol) was dissolved in dichloromethane (10 ml); Triethylamine (8.9 mmol), dimethylamine hydrochloride (8.9 mmol) and sodium triacetoxyborohydride (8.9 mmol) were added to the reaction mixture and the reaction mixture was stirred at room temperature for 16 hours. The pH value of the reaction mixture was adjusted to 9 with aqueous potassium carbonate solution, the mixture was extracted with dichloromethane, the organic phase was washed with saturated saline solution, dried over anhydrous sodium sulfate, filtered and The filtrate was evaporated to dryness to obtain 1.1 g of the crude target compound 3(4-bromophenyl)- / V, / V-dimethylcyclobutylamine (represented by 1-31-b) as a colorless oil, the yield was 97%. LC-MS: m / z: (Μ+Ηρ~ 255.4. Step 2: 3-(4-bromophenyl)- / V, / V-dimethylcyclobutylamine (1-31-b) (4.30 mmol) was dissolved in toluene (20 ml); and diphenylmethylamine (l-31-c) (4.8 mmol), sodium te / f-butoxide (6.9 mmol), 1,1'-binaphthyl-2,2'bis (diphenylphosphine) (0.43 mmol) and tris(d !benzylideneacetone)dipalladium (0.13 mmol) to the reaction mixture, then the reaction was heated to 90 ° C and stirred for 16 hours under the protection of nitrogen. The reaction mixture was cooled to room temperature and concentrated to obtain a crude product, and the crude product was purified by column chromatography (dichloromethane / methanei = 100 / 0-95 / 5) to obtain 1.5 g of the compound. target 3-(4((dipheniimethylenejamino)phenyl)- / V. / V-dimethylcyclobutanamine (1-31 -d) as a colorless oil, the yield was 98%. LC-MS: m / z: (M+H )^ 355.3. Step 3: 4-(3-dimethylamino)cyclobutii)aniline (1-31-d) (4.2 mmol) was dissolved in methane! (20 ml), sodium acetate (13.0 mmol) and hydroxylamine hydrochloride (8.5 mmol) were added to the reaction mixture and the reaction mixture was stirred at 50°C for 16 hours. The reaction mixture was evaporated to dryness to obtain a crude product and the crude product was purified by column chromatography (dichloromethane / methanol = 100 / 0-95 / 5) to obtain 0.75 g of the target compound 4-(3-dimethylamino). cyclobutyl) aniline (1-31 -e), the yield was 93%.5LC-MS: m / z: (M+HM 191.3. Step 4: 2-allyl·1-(7-hydroxy-7-methyl-6.7-d!hydro-5H-c¡clopenta[b]pyrid¡n-2-¡l)-6-(methylthio)-1,2-d Hydro3H-pyrazolo[3,4-D]pyrimidin-3-one (1-1-h) (0.65 mmol) was dissolved in toluene (20 ml), 3-chloroperoxybenzoic acid (0.62 mmol) was added and the mixture reaction was stirred for 0.5 hours at room temperature. 4-(3-dimethylamino)cyclobutii)aniline (1-31-e) (0.67 mmol) to the reaction mixture and the reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was evaporated to dryness to obtain a crude product, the crude product was suspended with ethyl acetate and dichloromethane to obtain 92 mg of the target compound 2allyl-6-((4-(3-(dimethylam) no)cyclobutyl)phenyl)amino)-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-1,25 dihydro-3H-pyrazolo[3,4-D]pyrimidin-3 -one (1-31) as a white solid, the yield was 32.9%.1H NMR (400 MHz, DMSO) δ 10.27 (s, 1 H), 8.89 (s. 1 H), 8.12 ( s, 1 H), 7.74 (dd, J = 22.6, 8.3 Hz, 3 H), 7.64 (d, J = 7.3 Hz, 1 H), 7.37 (d, J = 8.5 Hz , 2 H), 5.76-5.61 (m, 1 H), 5.34 (s, 1 H), 5.01 (dd, J = 10.3, 1.2 Hz, 1 H), 4.84 (re, J = 17, 1 Hz, 1 H), 4.70 (re, J = 5.7 Hz, 2 H), 3.62 (s, 1 H), 3.12 (s, 1 H), 2.71-2.58 (m, 8 H), 2.38 (d, J = 9.2 Hz, 2H), 1.47 (s,6H), 1.32-1.24 ΊΛ / t / ZUZZ / U I0400 (m, 1 H). LC-MS: m / z: (M+H)+= 500.3. Realization 32 Yo Compound (1-19-d) (80 mg, 0.1604 mmol, 100% by mass) was dissolved in ethanol (4 ml, 100% by mass), then water (2 ml, 100% by mass) and hydrochloride Hydroxylamine (3 equiv., 0.4813 mmol, 100% by mass) were added at room temperature and the reaction was stirred at 70°C for 12 hours. The reaction was quenched with an aqueous solution of NaHCO3 and extracted with ethyl acetate (2x20 mL), the organic phase was washed with saline solution (1 x20 mL), dried over NazSCU, filtered and concentrated to obtain a bud product. The crude product was washed with 2 mL of methanol and filtered to obtain the compound (I-32) (60 mg, 0.1137 mmol), the yield was 70.88%, white solid. Ή NMR (400 MHz, DMSO) δ 10.26 (s, 1 H), 8.88 (s, 1 Η), 8.07 (t, J = 7.8 Hz, 1 H), 7.76 (d, J = 8.0 Hz, 1 H), 7.65 (dd , J = 14.5, 7.9 Hz, 2 H), 7.22 (d, J = 8.5 Hz, 2 H), 5.74 - 5.60 (m, 1 H), 5.35 (s, 1 H), 5.00 (d, J = 10.3 Hz, 1 H), 4.83 (d, J = 17.1 Hz, 1H), 4.69 (d, J = 5.6 Hz, 2H), 3.74 (s, 3H), 3.24-3.15 (m, 1H), 2.77 (t, J = 12.0 Hz , 1H), 2.37 (d, J = 14.0 Hz, 1H), 2.25 (td, J = 13.4, 4.6 Hz, 1H), 1.99 - 1.84 (m, 3H), 1.67 - 1.50 (m .52H), 1.49 (d , J = 14.0 Hz, 6H).LC-MS: m / z: (M+H)r= 528. Realization 33 o o QQfrQ I η / 77Π7 / =1 / ΥΙΛ Step 1: Compound (S-15-c) (400 mg, 1.077 mmol) was dissolved in toluene (20 ml), then m-CPBA (1.2 equiv., 1.292 mmol, 77% by mass) was added at room temperature and The reaction was stirred for 2 hours at room temperature. Compound (l-33-a) (1.2 equiv., 1.292 mmol) and DIPEA (2 equiv., 2.154 mmol) were sequentially added to the above reaction mixture and the reaction continued with stirring at room temperature for 12 hours. The reaction was quenched with water and extracted with ethyl acetate (2 x 20 ml), the organic phase was washed with saline (1 x 20 ml), dried over Na2SO4, filtered and concentrated to obtain a crude product. The crude product was refined by a normal phase silica gel column (elution conditions: ethyl acetate / dichloromethane system, ethyl acetate concentration 0% to 10%, 24 column volumes) to obtain the compound (l -33-b): (120 mg, 0.2341 mmol), yield was 21.74%, yellow solid.1H NMR (400 MHz, DMSO) δ 8.91 (d, J = 2.4 Hz, 1 H), 8.11 (t, J = 7.9 Hz, 1 H), 7.89 (d, J = 8.3 Hz, 1 H), 7.68 (d, J = 8.2 Hz, 2 H), 7.57 (d, J = 7.7 Hz, 1 H), 7.28 (d, J = 8.6 Hz, 2 H), 5.72 (ddd, J = 23.0, 10.3, 5.9 Hz, 1 H), 5.02 (dd , J = 10.3, 1.3 Hz, 1 H), 4.95 - 4.89 (m, 2 H), 4.87 (d, J = 1.4 Hz, 1 H), 4.75 (d, J = 5.8 Hz, 1 H ), 4.70 (t, J = 6.2 Hz, 2H), 3.04 (t, J = 11.9 Hz, 1H), 2.67-2.53 (m, 2H), 2.30 (t, J = 15.0 Hz, 2H), 2.08 (d, J = 10.0 Hz, 2H), 1.96 - 1.81 (m, 2H). Step 2: Compound (i-33-b) (100 mg, 0.1951 mmol) was dissolved in meianol (3 ml); and DIPEA (5 equiv., 0.9754 mmol) was added and the reaction was stirred for 5 min at room temperature. Then, Na(OAc)3BH was added (3 equiv., 0.5853 mmol) and the reaction was continued with stirring at room temperature for 12 hours. The reaction was quenched with an aqueous NaHCO3 solution and extracted with ethyl acetate (2 x 20 mL), the organic phase was washed with saline solution (1 x 20 mL), dried over Na2SO4, filtered and concentrated to obtain a product. rough. The crude product was refined by a normal phase silica gel column (elution conditions: dichloromethane / methanol system (1% ammoniacal methanol), 0% to 10% methanol concentration, 12 column volumes) to obtain the Compound (I-33): (80 mg, 0.15 mmol), yield was 77.3%, white solid. Ή NMR (400 MHz, MeOD)50 8.86 (s, 0 H), 8.11-8.01 (m, 1 H), 7.94 (d, J = 7.9 Hz, 2 H), 7.67 (d, J = 7.6 Hz , 2 H), 7.62 (d, J = 8.6 Hz, 2 H), 7.28 (d, J = 8.5 Hz, 2 H), 5.83-5.74 (m, 1 H), 5.09 (dd, J = 7.9, 4.4 Hz, 3 H), 4.98 (dd, J = 17.1, 1.3 Hz, 2 H), 4.85 (d, J = 6.7 Hz, 2 H), 2.87 (s, 1 H ), 2.64 (s, 1 H), 2.47 (s, 3 H), 1.97 - 1.67 (m, 8 H LC-MS: m / z: (M+H)+= 529.2. Realization 34 Compound (I-33) (40 mg, 0.07582 mmol), cyclopropiacetic acid (1.1 eq., 73 mg) were dissolved in dichloromethane (2 mL), then DIPEA (2 equiv., 0.1516 mmol) and HATU ( 1 equiv., 0.07582 mmol) sequentially, and the reaction was stirred for 6 hours at room temperature. The reaction was quenched with water and extracted with dichloromethane (2 x 20 ml), the organic phase was washed with saline (1 x 20 ml), dried over Na2SO4, filtered and concentrated to obtain a crude product. The crude product was refined by a normal phase silica gel column (elution conditions: dichloromethane / methanol system, methanol concentration 0% to 10%, 12 column volumes) to obtain the compound (I-34): (10 mg, 0.01679 mmol), the yield was! 22.14%, yellow solid.1H NMR (400 MHz, MeOD) δ 8.87 (d, J = 6.6 Hz, 1 H), 8.06 (t, J = 7.9 Hz, 1 H), 7.95 (d, J = 7.9 Hz, 1 H), 7.68 (dd, J = 7.8, 5.4 Hz, 2 H), 7.61 (d, J = 8.6 Hz, 1 H), 7.41 (d, J = 8.4 Hz, 1 H), 7.24 (t, J = 8.7 Hz, 1 H), 5.84 - 5.72 (m , 1 Η), 5.09 (d, J = 6.2 Hz, 2H), 5.07 (d, J = 1, 3 Hz, 1H), 5.02 - 4.94 (m, 2H), 4.90 (s, 2H), 4.84 (d, J = 6.7 Hz, 2 H), 3.15 (d, J = 2.6 Hz, 1 H), 3.08 (s, 1 H), 2.95 (s, 1 H), 2.71 (s, 1 H), 2.43 (s, 1 H), 1.93-2.03 (m, 3 H), 1.76 (s, 2 H) ), 1.51 (s, 1 H), 1.31 (d, J = 4.3 Hz, 3 H), 0.89 (dd, J = 20.1, 9.0 Hz, 4 H). LC-MS: m / z; (M H)+ = 596.2. Realization 35 QQfrQ Ln / 77n7 / q / YIA Step 1: Compound (l-35-a) (100 mg, 0.3444 mmol) was dissolved in tetrahydrofuran (5 ml) and TEA (5 equiv., 1.722 mmol) and compound (!-35-b) (2 equiv., 0.6887 mmol) and the reaction was stirred for 8 hours at room temperature. The reaction was quenched with water and extracted with ethyl acetate (2 x 20 ml), the organic phase was washed with saline (1 x 20 ml), dried over Na2SO4, filtered and concentrated to obtain a crude product. The crude product was refined by a normal phase silica gel column (elution conditions: petroleum ether / ethyl acetate system, ethyl acetate concentration 10% to 60%, 12 column volumes) to obtain the Compound (i-35-c): (100 mg, 0.2532 mmol), yield was 73.54%, white solid. LC-MS: m / z: (M+H-tBu)= 339.1. Step 2: Compound (l-35-c) (200 mg, 0.5065 mmol) was dissolved in tetrahydrofuran (5 ml), then sodium hydride (2 equiv., 1.013 mmol, 60% by mass) was added and the reaction was stirred for 2 hours at 50°C. The reaction was quenched with water and extracted with ethyl acetate (2 x 20 ml), the organic phase was washed with saline solution (1 x 20 ml), dried over Na2SO4, filtered and concentrated to obtain the compound (l- 35-d): (180 mg, 0.502 mmol), yield was 99.14%, white solid.1H NMR (400 MHz, MeOD) 67.31 (dt, J = 11.6, 8.5 Hz, 3 H) , 7.15 (d, J = 8.5 Hz, 1 H), 4.07-3.92 (m, 1 H), 3.47 (dt, J = 29.5, 7.2 Hz, 2 H), 2.39 (dt, J = 16.3, 8.1 Hz, 2 H), 2.22 (d, J = 10.1 Hz, 1 H), 2.03 (s, 4 H), 1.84-1.57 (m, 6 H), 1.53 (d. J = 2.8 Hz, 9 H). LC-MS: m / z: (M+H)+= 359.1. Step 3: Compound (l-35-d) (180 mg, 0.669 mmol) was dissolved in dichloromethane (4 ml), then trifluoroacetic acid (1 ml) was added and the reaction was stirred for 12 hours at room temperature. After the reaction mixture was concentrated, an aqueous NaHCO3 solution was added and the mixture was extracted with ethyl acetate (2 x 20 ml); The organic phase was washed with saline solution (1 x 20 mL), dried over Na2SO4, filtered and concentrated to obtain the compound (l-35-e): (120 mg, 0.464 mmol), the yield was 100%, yellow solid. LC-MS: m / z: (M+H)+= 259.1. Step 4: Compound (1-15-c) (100 mg, 0.2693 mmol) was dissolved in toluene (2 ml), then m-CP8A (1.2 equiv., 0.3231 mmol, 77% by mass) was added. at room temperature and the reaction was stirred for 2 hours at room temperature. Compound (l-35-e) (1.2 equiv., 0.3231 mmol) and DIPEA (2 equiv., 0.5385 mmol) were added sequentially to the above reaction mixture ^5 at room temperature and the reaction continued with stirring at room temperature for 12 hours. The reaction was quenched with water and extracted with ethyl acetate (2 x 20 ml), the organic phase was washed with saline (1 x 20 ml), dried over Na2SO4, filtered and concentrated to obtain a crude product. The crude product was refined by a normal phase silica gel column (elution conditions: dichloromethane / tetrahydrofuran system, 0% to 30% tetrahydrofuran concentration, 12 column volumes) to obtain the compound (I-35): (40 mg, 0.06876 mmol), yield was 25.54%, white solid.1H NMR (400 MHz, CDCI3) 5 8.87-8.79 (m, 1H), 8.14-8.07 (m, 1H), 8.04 -7.96 (m, 1H), 7.89-7.80 (m, 1H), 7.61-7.50 (m, 2H), 7.38-7.32 (m, 1H), 7.25 - 7.19 (m , 1H), 7.01 (t, J = 3.4 Hz, 1H), 5.72 (ddd, J = 16.6, 11.1, 8.6 Hz, 1H), 5.17-5.09 (m, 2H)), 5.04- 4.98 (m, 1H), 4.98 - 4.92 (m, 1H), 4.87 -254.77 (m, 2H), 4.73 - 4.64 (m, 2H), 4.20 - 4.06 (m, 1H), 3.47 - 3 .38 (m, 1H), 3.38 - 3.29 (m, 1H), 3.05-2.98 (m, 1H), 2.49-2.35 (m, 2H), 2.27-2.17 (m, 1H), 2.07-1.86 (m, 4H), 1.75-1.60 (m, 3H). LC-MS: m / z: (M+H)- 582.2. Realization 36 QQfrQ Ln / 77n7 / q / YIA 2-Allyl-1-(6-(3-hydroxyoxetan-3-yl)pyridin-2-yl)-6-(methylthio)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3 -one (represented by formula 1-15-c) (200 mg, 0.538 mmol) was dissolved in 5 ml of toluene and 3-doroperoxybenzoic acid (140 mg, 0.69 mmol) was added and the reaction mixture was stirred at 20 °C for 2 hours. The reaction mixture was concentrated to dryness under reduced pressure. The solid obtained was dissolved in 5 mL of DMSO and trifluoroacetic acid (20 mg, 0.2 mmol) and 4-(4-(azetidin-1 -yl) cyclohexyl)aniline (represented by the formula l-36-a) ( 140 mg, 0.64 5 mmol) and the reaction mixture was stirred at 65°C for 16 hours. The reaction was quenched with water and then extracted with dichloromethane (30 ml x 3), the organic layer was dried over anhydrous sodium sulfate, concentrated and purified by column chromatography (methanol / dicioromethane / ethyl acetate = 0. 5: 10:4 to 1:10:4) to obtain a yellow solid (I36-2) (22 mg, 7.4%) and a yellow solid (1-36-1) (64 mg, 21.4% ). Compound 1-36-1: HPLC retention time (RT) = 7.14 min (HPLC conditions: mobile phase A was water (containing 0.1% HCOOH), mobile phase B was acetonitrile; elution in gradient: 5% mobile phase B 95% mobile phase B),1H NMR (400 MHz, CDCI3) S8.88 (d, J = 2.6 Hz, 1 H),8.09 (dd, J = 15.0, 7.8 Hz, 1 H), 7.99-7.83 (m, 2 H), 7.54 (t, J = 9.5 Hz, 2 H), 7.39 (d, J = 8.7 Hz, 1 H), 7.21 (d , J = 8.5 Hz, 1 H), 5.74 (dq, J = 10.5, 5.9 Hz, 1 H), 5.12 (t, J = 8.8 Hz, 3 H), 4.99 (d, J = 17, 1 Hz, 1 H), 15 4.80 (d, J = 6.3 Hz, 2 H), 4.67 (d, J = 6.0 Hz, 2 H), 3.39-3.24 (m, 4 H), 2.60-2.34 (m, 3H), 2.14 (dt, J = 14.0,6.8 Hz, 3H), 1.96 (d, J = 10.8 Hz, 4H), 1.55-1.37 (m , 2 H), 1.27-1.12 (m, 2 H); LCMS: m / z: (M+H)+= 554.1. Compound I-36-2: HPLC retention time (RT) = 7.15 min (HPLC conditions: mobile phase A was water (containing 0.1% HCOOH), mobile phase B was acetonitrile; elution in gradient: 5% mobile phase B 95% mobile phase B),1H NMR (40020MHz, MeOD) 68.86 (s, 1 H), 8.02 (dt, J = 24.0, 7.9 Hz, 3 H), 7.64 (dd, J = 27.1, 8.1 Hz, 3 H), 7.27 (t, J = 8.6 Hz, 2 H), 7.01-6.91 (m, 3 H), 6.72-6.64 (m, 3 H), 5.79 (ddd, J = 16.3, 11.2, 6.1 Hz, 1 H), 5.10-5.05 (m, 2 H), 4.85 (d, J = 6.8 Hz, 2H), 2.57 (d, J = 10.7 Hz, 1H), 2.48-2.28 (m, 3H), 2.23-2.06 (m, 3H), 1.98-1.71 (m, 6H), 1.58 (dd, J = 23.2, 12.9 Hz, 3H), 1.44 (ddd, J = 16.1, 13.2, 3.5 Hz, 2H), 1.19-1.00 (m, 2H); LO- MS: m / z: (M+H)+= 554.1. 25Realization 37 100 Step 1: Compound (l-35-a) (150 mg, 0.5165 mmol) was dissolved in tetrahydrofuran (6 ml) and DIPEA (5 equiv., 2.583 mmol) and compound (l-35-a) (3 equiv., 1,550 mmol) and the reaction was stirred for 12 hours at room temperature. The reaction was quenched with water and extracted with ethyl acetate (2 x 20 ml), the organic phase was washed with saline solution (1 x 20 ml), dried over Na2SO4, filtered and concentrated to obtain a crude product. The crude product was refined by a column of ge! of normal phase silica (elution conditions: petroleum ether / ethyl acetate system, ethyl acetate concentration 0% to 40%, 12 column volumes) to obtain compound (l-37-b): ( 120 mg, 0.3023 mmol), yield was 58.53%, white solid.1H NMR (400 MHz, MeOD) δ 7.38-7.27 (m, 2 H), 7.24 -7, 18 (m, 1 H), 7.18-7.09 (m, 1 H), 4.38-4.23 (m, 2 H), 3.83-3.67 (m, 2H). 2.63 (td, J = 14.1.6.0 Hz, 1H), 2.522.37 (m, 1H), 2.31 (S, 1H), 2.25-2.13 (m, 1H), 2.00-1.84 (m, 3H)), 1.82- 1.63 (m,3H), 1.53 (s. 9 H). Step 2: Compound (l-37-b) (120 mg, 0.30 mmol) was dissolved in tetrahydrofuran (5 ml), then sodium hydride (2 equiv., 0.607 mmol, 60% by mass) was added and the reaction was stirred. for 2 hours at 50°C. The reaction was quenched with water and extracted with ethyl acetate (2 x 20 ml), the organic phase was washed with saline solution (1 x 20 ml), dried over Na2SO4, filtered and concentrated to obtain the compound (l- 37-c): (80 mg, 0.22 mmol), the yield was 73.4%, white solid. Ή NMR (400 MHz, MeOD) 57.31 (dt, J = 18.7, 8.6 Hz, 3 H), 7.15 (d, J = 8.5 Hz, 1 H), 4.42-4.26 ( m, 2 H), 3.66 (ddd, J = 16.1, 12.2, 5.9 Hz, 2 H), 2.50 (s, 1 H), 2.15 (dd, J= 17.3, 6.4 Hz, 2H), 1.99-1.79 (m, 4 H), 1.77-1.61 (m, 3 H), 1.53 (d, J = 1.7 Hz, 9 H). LC-MS: m / z: (M+Hi= 305.1. Step 3: 101 Compound (l-37-c) (80 mg, 0.22 mmol) was dissolved in dichloromethane (2 ml), then trifluoroacetic acid (1 ml) was added and the reaction was stirred for 12 hours at room temperature. The reaction mixture was concentrated and then aqueous NaHCO3 was added and the mixture was extracted with ethyl acetate (2 x2Q mL), the organic phase was washed with saline solution (1 x 20 5 mL), dried over Na2SO¿, filtered and concentrated to obtain a crude product. The crude product was refined by a normal phase silica gel column (elution conditions: petroleum ether / ethyl acetate system, 0% to 50% ethyl acetate concentration, 12 column volumes) to obtain the compound (l-37-d): (60 mg, 0.2305 mmol), yield was 100%, yellow solid. Ή NMR (400 MHz, MeOD) δ 7.11 (d, J - 8.1 Hz, 1 H),107.00 (d, J = 8.3 Hz, 1 H), 6.78-6.66 (m, 2 H) , 4.40-4.29 (m, 2 H), 3.70-3.57 (m, 4 H), 2.10 (d, J = 17.5 Hz, 1 H), 1.97-1.81 (m, 4 H), 1.72-1.57 (m, 3 H). LC-MS: m / z: (M+H)+= 261.1. Step 4: Compound (1-15-c) (60 mg, 0.1616 mmol) was dissolved in toluene (2 ml), then m-CPBA (1.2 equiv., 0.1939 mmol, 77% by mass) was added. at room temperature and the reaction ^5 was stirred for 2 hours at room temperature. Compound (l-37-d) (1.4 equiv., 0.2262 mmol) and DIPEA (2 equiv., 0.3231 mmol) were sequentially added to the above reaction mixture at room temperature and the reaction continued with stirring. at room temperature for 12 hours. The reaction was quenched with water and extracted with ethyl acetate (2 x 20 ml), the organic phase was washed with saline solution (1 x 20 ml), dried over Na2SO4, filtered and concentrated20 to obtain a crude product. The crude product was refined by a normal phase silica gel column (elution conditions: dichloromethane / tetrahydrofuran system, tetrahydrofuran concentration 0% to 50%, 12 column volumes) to obtain the compound (I-37): (15 mg, 0.02570 mmol), the yield was 15.91%, yellow solid. Ή NMR (400 MHz, CDCh) S8.77 (s, 1H), 8.16-8.07 (m, 1H), 8.03 (d, J = 7.6 Hz, 1H), 7.83-7.75 (m, 1H),257 .56 (dd, J = 12.6, 6.1 Hz, 2H), 7.33 (d, J = 8.5 Hz, 1H), 7.21 (d, J = 8.5 Hz, 1H), 5.72 (dd, J = 17.0, 10.3 Hz, 1H), 5.13 (dd, J = 9.1,6.1 Hz, 2 H), 4.96 (d, J = 17.0 Hz, 2 H), 4.81 (d, J = 7.2 Hz, 2 H), 4.69 (d, J = 6.2 Hz, 2 H), 4.41 - 4.28 (m, 2 H), 3.86 (s, 1 H), 3.77 (t, J = 6.6 Hz, 1 H), 3,633.50 (m, 2H), 2.98 (m, 1 H), 2.15 (m, 1 H), 1.97 (dd, J = 18.9,9.6 Hz, 2 H) , 1.78 (d, J = 5.0 Hz, 2 H), 1.65 (d, J = 8.7 Hz, 2 H). LC-MS: m / z: (M+H)*= 584.1. Realization 38 102 IVIA / t / ZUZZ / U I0400 Compound (l-33-a) (150 mg, 0.79260 mmol) was dissolved in dichloromethane (2 ml) and then (Boc)2O (1.2 equiv., 0.95112 mmol) and DIPEA (2 equiv., 1 .5852 mmol) and the reaction was stirred at room temperature for 12 hours. The reaction was quenched with water and extracted with dichloromethane (2 x 20 ml), the organic phase was washed with saline solution (1 x 20 ml), dried over Na2SO4, filtered and concentrated to obtain the compound (l-38 -a): (250 mg, 0.8639 mmol), yield was 100.0%, yellow solid.1H NMR (400 MHz, DMSO) δ 9.25 (s, 1 H), 7.37 (d, J = 8, 4 Hz, 2 H), 7.17 (d, J = 8.6 Hz, 2 H), 2.98 (ddd, J = 12.0, 8.7, 3.3 Hz, 1 H), 2.65 - 2.52 (m, 2 H), 2.25 (dd, J = 12.5, 2.0 Hz, 2 H), 2.11 - 1.97 (m, 2 H), 1.83 (ddd, J = 25.9, 20 13.2, 4.0 Hz, 2 H), 1.47 (s, 9H). Step 2: Potassium ferf-butoxide (3 equiv., 1.866 mmol) was dissolved in dry tetrahydrofuran (1 ml), and then a solution of tosylmethyl isocyanide (1.5 equiv., 0.933 mmol) in dry tetrahydrofuran (1 ml) was added. at room temperature. Compound (l-38-a) (180 mg, 0.6220 mmol) was dissolved in dry methanol (0.5 ml), the solution was added to the above reaction mixture and then the reaction was stirred at room temperature for 12 hours . The reaction was quenched with water and extracted with ethyl acetate (2 x 20 ml), the organic phase was washed with saline solution (1 x 20 ml), dried over Na2SO4, filtered and concentrated to obtain a crude product. The crude product was refined by a normal phase silica gel column (elution conditions: dichloromethane system, methanol, methanol concentration from 0% to 10%, 12 column volumes) to obtain the compound (l- 38-b): (60 mg, 0.1997 mmol), the yield was 32.11%, yellow solid. LC-MS: m / z: (M+H)+= 244.7. Step 3: Compound (l-38-b) (50 mg, 0.16 mmol) was dissolved in dichloromethane (2 ml), then trifluoroacetic acid (1 ml) was added and the reaction was stirred for 12 hours at room temperature. After the reaction mixture was concentrated, a solution was added 103 watery. NaHCO3 was added and the mixture was extracted with ethyl acetate (2 x 20 ml); The organic phase was washed with saline solution (1 x 20 mL), dried over Na2SO4, filtered and concentrated to obtain the compound (l-38-c): (50 mg, 0.159 mmol), the yield was 96%, yellow solid. LC-MS: m / z: (M+H)+= 201.1. Step 4: Compound (l-15-c) (50 mg, 0.1346 mmol) was dissolved in toluene (2 ml), then m-CPBA (1.2 equiv., 0.1616 mmol, 77% by mass) was added. at room temperature and the reaction was stirred for 2 hours at room temperature. Compound (l-38-c) (50 mg, 0.1346 mmol) and DIPEA (2 equiv., 0.2693 mmol) to the above reaction mixture at room temperature sequentially, and the reaction continued with stirring at room temperature for 12 hours. The reaction was quenched with water and extracted with ethyl acetate (2 x 20 ml), the organic phase was washed with saline (1 x 20 ml), dried over Na2SO4, filtered and concentrated to obtain a crude product. The crude product was refined by a normal phase silica gel column (elution conditions: dichloromethane / tetrahydrofuran system, tetrahydrofuran concentration 0% to 30%, 12 column volumes) to obtain the compound (I-38): (10 mg, 0.01910 mmol), yield was 14.19%, white solid.1H NMR (400 MHz, CDCI3) δ 8.69 (s, 1H), 8.18 (d, J = 8.0 Hz, 1H), 8 .10 (dd, J = 17.9, 7.6 Hz, 1H), 7.81- 7.72 (m, 1H), 7.63-7.49 (m, 2H), 7.25 (d, J = 8.4 Hz, 1H) , 7.19 (d, J = 8.3 Hz, 1H), 5.70 (d, J = 6.8 Hz, 1H), 5.15 (d, J = 10.1 Hz, 1H) , 5.14 - 5.07 (m, 1H), 4.95 (d, J = 16.6 Hz, 1H), 4.83 (t, J = 6.7 Hz, 2H), 4.71 (s, 2H), 2.54 (dd, J = 24.9, 12.6 Hz, 2H), 2.30 (d, J = 11.2 Hz, 1H), 2.18 (d, J = 13.5 Hz, 1H), 2.02 (d, J = 12.9Hz, 1H), 1.96-1.80 (m, 2H), 1.78 (d, J = 16.1 Hz, 1 H), 1.49 (dd, J = 26.4, 11.2 Hz, 2 H). LC-MS: m / z: (M+H)+= 524.1. Realization 40 Compound (1-39) (70 mg, 0.12 mmol) was dissolved in a mixture of ethanol (2 ml), tetrahydrofuran (2 ml) and water (2 ml), then lithium hydroxide monohydrate (15 mg, 0.36 mmol) and the reaction mixture was concentrated after stirring at room temperature for 16 hours; The reaction mixture was purified by thin layer chromatography (dichloromethane: ammonia methanol (7 M): ethyl acetate = 7:1:1) to obtain a white solid (I-40) (40 mg, 60%). Ή NMR (400 MHz, methanol-d4) δ 8.84 (s, 1 H), 8.05 (t, J = 7.9 Hz, 1 H), 7.92 (d, J = 8.1 104 Ηζ, 1 Η), 7.66 (dd, J = 7.6, 0.9 Ηζ, 1 Η), 7.63 - 7.53 (m, 2Η), 7.22 - 7.14 (m, 2Η), 5.84 - 5.74 (m , 1H), 5.10-5.07 (m, 2H), 5.06 (q, J = 1.3 Ηζ, 1H), 4.98 (dq, J = 17.0, 1.4 Hz, 1 H), 4.89 (di, J = 6.1, 1.4 Hz, 2 H), 2.71 (d, J = 6.9 Hz, 1 H), 2.59 (s, 1 H), 2.24 (dd, J = 16.4, 7.8 Hz , 2 H), 2.04 (d, J = 8.5 Hz, 1 H), 1.73 (td, J = 10.9, 6.8 Hz, 6 H). LC-MS: m / z: [M+lf = 543.0. Realization 41 IVIA / t / ZUZZ / U I0400 Compound (1-41-1) and compound (1-41-2) can be synthesized by the same method as in embodiment 1 using 5-bromo-2-nitropyridine as raw material. Compound 1-41-1: HPLC retention time (RT) = 6.17 min (HPLC conditions: mobile phase A was water (containing 0.1% HCOOH), mobile phase B was acetonitrile; elution in gradient: 5% mobile phase B 95% mobile phase B),1H NMR (400 MHz, chloroform-d) δ 9.00 (s, 1 H), 8.30 (d, J = 8.6 Hz, 1 H), 8 .22 (d, J = 2.4 Hz, 1 H), 7.96 (t, J = 7.9 Hz, 1 H), 7.73 (dd, J = 8.1, 0.8 Hz, 1 H), 7.55 ( dd, J = 8.7, 2.4 Hz, 1 H), 7.44 (dd, J = 7.7, 0.8 Hz, 1 H), 5.77 - 5.66 ( m, 1H), 5.12 - 5.05 (m, 1H ), 4.97 (dq, J = 17.0, 1.4 Hz, 1H), 4.76 (dt, J = 6.3, 1.3 Hz, 2H), 2.70 (s, 1H), 2.56 (s, 6 H) , 20 2.23 (q, J = 9.5 Hz, 4 H), 2.11 - 2.01 (m, 4 H), 1.58 (t, J = 10.3 Hz, 6 H). LC-MS: m / z: [Μ+1Γ = 529.1. Compound 1-41-2: HPLC retention time (RT) = 6.28 min (HPLC conditions: mobile phase A was water (containing 0.1% HCOOH), mobile phase B was acetonitrile; elution in gradient: 5% mobile phase B > 95% mobile phase B),1H NMR (400 MHz, chloroform-d) S8.99 (s, 1 H), 8.54 (s, 1 H), 8.32 (d , J = 8.7 Hz, 1 H), 8.26 (d, J = 2.4 Hz, 1 H), 8.10 (t, J = 7.7 Hz, 1 H), 25 7.92 (s, 1 H) , 7.78 (dd, J = 8,1,0.8 Hz, 1 H), 7.47 - 7.41 (m, 1 H), 5.79 - 5.71 (m, 1 H) , 5.08 (dq, J = 10.1, 1.2 Hz, 1H),4.97 (dq, J = 17.0, 1.3 Hz, 1H),4.77 (dt, J = 6.2, 1.4 Hz, 2H), 3.99 (s, 1H), 2.75 (d, J = 11.0 Hz, 1 H), 2.52 (s, 6 H), 2.32-2.18 (m, 1 H), 2.09 (d, J = 14.4 Hz, 4 H), 1.31 (d, J = 22.8 Hz, 4 H). LC-MS: m / z: [M+1 ]+= 529.1. With reference to the above embodiments, the compounds shown in Table 1 were prepared, and their structural characteristics were as follows: 105 Table 1 Lysia of compounds Compound Structure Characterization data Method I-2 0 ?! I N—z v % 0 0 !H NMR (400 MHz, MeOD) δ 8.85 (s, 1 H), 8.00 (t, J = 7.9 Hz, 1 H), 7.80 (d, J = 8.1 Hz, 1 H ), 7.68 (d, J = 7.7 Hz, 1 H)), 7.62 (d, J = 8.6 Hz. 2 H). 7.28 (d, J = 8.6 Hz. 2 H). 5.78 5.68 (m, 1 H). 5.06 (d, J = 10.3 Hz. 1 H), 4.95 (s , 1H), 4.82 (s. 2H), 3.82 - 3.76 (m, 1H). 2.81 (s, 1H). 2.71 is, 3H). 2.49 is, 1H). 2.08 (d. J = 10.9 Hz, 3 H), 1.94 (d, J = 15.0 Hz. 3 H), 1.72 (s, 4 H), 1.59 (d. J = 7.0 Hz, 6 H). LC-MS: m / z: (M+H)+ = 570.3. 1-1 I-8 0 N -^r-X / “ H I N~y A ^-N y N 18 1H NMR (400 MHz. CDC!3) δ 8.86 ís, 1 H). 7.93 - 7.85 (m, 1 H), 7.78 (d, J = 7.8 Hz, 1 H), 7.52 (d. J = 8.5 Hz. 2 H). 7.39 (dd, J = 7.6, 0.7 Hz, 1 H), 7.19 (d, J = 8.5 Hz, 2 H), 5.71 (ddt, J = 16.4, 10.2, 6.2 Hz, 1 H) , 5.05 (dd, J= 10.2, 1.1 Hz, 1 H),4.94 (dd, J= 17.1, 1.3 Hz, 1 H), 4.77 (d, J= 6.2 Hz, 2 H ), 4.11 (d, J = 8.9 Hz, 1 H), 3.24 (t, J = 7.0 Hz, 4 H). 2.52 - 2.43 (m, 1H). 2.14 - 2.00 (m, 3 H), 1.92 (d, 11.2 Hz, 4H), 1.60 (s, 6 H), 1.45 (dt. J = 14.9, 7.5 Hz, 2 H), 1.23 - 1.08 (m, 2 H). LC-MS: m / z: (M+H)” = 540.4. I-I See embodiment 8 for more details. 1-8-1 0 N'^-X / = ¿ x1 -N HN^ 0 oí Y OH 0 / > ί8-' NMR (400 MHz, CDCI3) δ 8.86 (s, 1 H), 7.93 - 7.85 (m , 1 H), 7.78 (d, J = 7.8 Hz. 1 H), 7.52 (d. J = 8.5 Hz, 2 H), 7.39 (dd, J = 7.6, 0.7 Hz, 1 H), 7.19 (d. J - 8.5 Hz, 2 H). 5.71 íddt, J = 16.4. 10.2, 6.2Hz, 1H). 5.05 (dd. J= 10.2, 1.1 Hz. 1 H), 4.94 idd, J= 17.1, 1.3 Hz. 1 H), 4.77 (d, J= 6.2 Hz, 2 H), 4.11 ( d. J = 8.9 Hz. 1 H), 3.24 (t, J = 7.0 Hz, 4 H), 2.52 - 2.43 (m, 1 H), 2.14 - 2.00 (m, 3 H ), 1.92 (d, 11.2 Hz, 4H), 1.60 (s, 6H). 1.45 (dt. J = 14.9, 7.5 Hz, 2 Η), 1.23 - 1.08 (m, 2 H). LC-MS: m / z: (M+H)+ = 540.4. After testing, its retention time was unique: HPLC retention time (RT) = 10.78 min (HPLC conditions: mobile phase A was water (containing 0.1% HCOOH), mobile phase B was acetonitrile; gradient elution: 5% mobile phase B -> 50% mobile phase B). Therefore, its cyclohexyl moiety was cis 0 trans. This can be further corroborated by joint realization 8-2. 1-1 See embodiment 8-1 for details. 106 I-8-2 0 «Ύ / — J .J. .N HN Ν' 'N, 6 Cu 0 Ñ 1-8-2 4H NMR (400 MHz, CDCI3) 68.87 (s, 1 H), 7.92 (d, J = 7.8 Hz, 1 H), 7.80 (d, J = 8.0 Hz, 1 H), 7.52 (d, J = 8.4 Hz, 2 H), 7.39 id, J = 7.6 Hz, 1 H), 7.29 - 7.25 (m, 2 H) ), 5.82-5.63 (m, 1 H), 5.12-4.91 (m, 2 H), 4.78 (d, J - 6.2 Hz, 2 H), 4.01 (s , 1 H), 3.17 (s, 4 H), 2.53 (s, 1 H), 2.33 (s, 1 H), 2.06 (d, J = 4.4 Hz, 2 H), 1.89 (d, J = 11.6 Hz, 2 H), 1.75 (d, J = 14.1 Hz. 2 H), 1.59 (d, J = 17.2 Hz, 8 H), 1.46 (t, J = 13.1 Hz, 2 H ). LC-MS: 540.0 [M 1], HPLC retention time (RT) = 10.997 min (HPLC conditions: mobile phase A was water (containing 0.1% HCOOH), mobile phase B was acetonitrile; gradient elution: 5% mobile phase B 50% mobile phase B). See embodiment 8-2 0 embodiment 8-3 1-17 0 / = A A 0 0 Á Λ 1-17 H 1H NMR (400 MHz. CDCI3) δ 8.84 (d. J = 3.7 Hz, 1 H), 7.94 (dd , J = 14.8, 6.9 Hz, 1 H). 7.76 (d, J = 7.9 Hz, 1H), 7.58 - 7.50 (m, 2H). 7.42 id. J = 7.5, 4.1 Hz, 1H). 7.22 (dd. J = 15.8, 8.5 Hz, 2H), 5.71 (dd, J = 11.5, 5.4 Hz, 2H), 5.07 (d, J = 10.2 Hz, 1 H), 4.95 (d, J = 17.1 Hz, 1 H), 4.77 (d, J = 6.1 Hz, 2 H), 2.82 - 2.72 (m, 1 H), 2.60 (s, 1 H). 2.12 - 2.01 (m, 3 H), 1.92 (d, J = 12.5 Hz, 1 H), 1.81 - 1.67 (m. 3 H), 1.62 (s, 6 H). 1.54 - 1.43 (m, 1 H), 0.93 - 0.78 (m, 3 H). 0.52 (s, 2H). LC-MS: m / z: (M+H)' = 568.4. I-7 I-39 p A'A-A |i J N-7 ηνλΥ or OH Q Ί Í-3S COOEt 1H NMR (400 MHz, methanol·^) δ 8.85 (d, J = 1.1 Hz, 1 H) , 8.05 (td, J= 7.9, 4.8 Hz, 1 H), 7.96 - 7.86 (m, 1 H), 7.67 (d, J = 7.6 Hz. 1 H), 7.59 (ddd, J = 9.2. 4.6 , 2.3 Hz, 2H), 7.25 -7.19(m, 1H). 7.19-7.11 (m. 1H),5.78 (ddt. J = 16.5, 10.1, 6.1 Hz. 1 H). 5.12 - 5.07 (m. 2 H), 5.06 (t. J = 1.3 Hz. 1 H), 4.98 (dd, J = 17.0, 1.4 Hz. 1 H), 4.90 (d. J= 1.4 Hz, 2 H), 4.25 - 4.19 (m, 1 H), 4.14 (dd, J= 14.1, 7.1 Hz, 1 H), 2.34 - 2, 12 (m, 2H), 2.07 (dd, J = 17.0, 4.1 Hz, 1H), 1.99 - 1.82 (m, 1H), 1,741.65 (m. 2H), 1.65 - 1.53 (m, 2H) ), 1.31 (d, J = 4.2 Hz. 3 H). 1.29 - 1.25 (m, 2H). LC-MS: m / z: [M+1]+= 571.1. I-4 IVIA / t / ZUZZ / U 10400 Effect Realization 1 / . Inhibitory effect of the compound on WEE1 kinase in vitro Testing method: The tested compounds were screened on WEE1 kinase with ATP concentration by Kmby ELISA. Compounds were screened on WEE1 kinase to evaluate the kinase inhibitory activity of the tested compounds. In the detection process, the initial concentration of the tested compounds was selected as 100 nM, and each 107 compound was selected with 6 gradient dilution concentrations, the gradient dilution ratio was 4 times higher and two replicate wells were detected for each concentration, MK1775 was used as a standard control. WEE1, acquired from CarnaBiosciences, Inc., item #05-177; dimethyl sulfoxide, purchased from Sigma-Aldrich, item #D8418; ATP, purchased from Sigma-Aldrich, item #A7699; DTT solution, purchased from Sigma-Aldrich, item #43816; protein tyrosine kinase (PTK) substrate (poly-Glu-Tyr), purchased from Sigma-Aldrich, item #P4476; P-Tyr (PY99), purchased from Santa Cruz, item # sc-7020; Mouse anti-lgG HRP-linked antibody, purchased from Santa Cruz, item #7076S; TMB Liquid Substrate System, purchased from Sigma-Aldrich, item number T0440; Costar Stripweli microplate without lid 1 χ 8 piano bottom, certified high union, purchased from Sigma-Aldrich, item # 42592; 96-well composite plate, purchased from Thermo Scientific, item no. #267245, Test steps: 1. Coating substrate: 1) An appropriate volume of protein tyrosine kinase (PTK) substrate storage solution (poly-Glu-Tyr) substrate was taken, diluted 10 times with PBS, and the concentration was diluted to 250 mg / ml to 25 mg / ml. The mixture was added to a high adsorption 96-well plate at 125 pL per well. The plate was placed in a 37 °C incubator to cover overnight. 2) After 24 hours, the 96-well plate was taken out, the liquid was poured out of the 96-well plate, cleaned with wash buffer 3 times, and the incubator was inverted to 37°C and dried for 2 hours. 2. Preparation and transfer of compounds: 1) compound dilution: 10 mM of the test compound stock solution was taken, the compound in a 96-well compound plate was diluted with DMSO in multiple steps to obtain the initial concentration of 100x compound as the first concentration, and then DMSO was used for a 4-fold dilution gradient, for a total of 6 concentrations; after that, 2 μ of the gradient dilution solution was added to 48 pL of 1 χ reaction buffer respectively to prepare 4x compound; 2) 4 x compounds were transferred: 10 pL of 4 χ compounds from the 96-well compound plate configured in the previous step were transferred to the dry high adsorption 96-well plate; 10 pL of the following liquids were added to the control wells without compound and to the ATP control wells: 2 pL of DMSO was added to 48 pL of 1x reaction buffer. 3. Enzymatic reaction step: 1) WEE1 kinase and ATP were prepared in 2x enzyme solution and 4x ATP solution respectively with 1x reaction buffer. In this selection, the final concentration of WEE1 kinase was: 0.15 ng / pL and the final concentration of ATP was: 12 pM; 2) 20 pL of enzyme solution 2 was added to the 96-well plate of 108 adsorption; 3) 10 μ of 4*ATP solution was added to the 96-well adsorption plate and 10 pL 1x of reaction buffer was added to the ATP control group; 4) The plate was placed in a HERAEUS Multifuge X1R centrifuge at 2000 rpm for 20 s and then placed at room temperature and reacted for 60 min. 4. Reaction determination step: 1) the reaction mixture was poured into the plate. 200 pL of wash buffer was added to each well and washed 5 times; the primary antibody PTyr (PY99) (dilution ratio 1:2000), 100 pL per well, at room temperature for 30 min. 2) The primary antibody was poured into the plate. 200 pL was added to each L well of wash buffer and washed 5 times; The second antibody Anti-ray IgG HRP-linked antibody was added (dilution ratio 1:2000), 100 pL per well, at room temperature for 30 min. 3) The secondary antibody was poured into the plate, washed 5 times with washing buffer and TMB was added, 10 OpL per well and colored for 10-30 min, depending on the depth of color. The reaction was terminated with 1 N sulfuric acid before reading. 5. Data detection and processing: 1) Light absorption at 450 nM was read on ThermoScieníific MultiScan GO and background was read at 650 nM at the same time. 2) Graphpad Prism 5.0 was used to fit the Log (inhibitor) vs. curves. Response-variable slope (four parameters) to the data, and the corresponding IC5o (half the maximal inhibitory concentration) was calculated. II. The test result data. The structure of the control samples used in the tests is shown in Table 2. Table 2 Structure of the control sample Control Sample Number Chemical Structure Control 1 (AZD1775 / MK1775) 0 NM / = ji Λ HN' 'N ’N U O-Y r oh Q I The test results were detailed in Table 3. Table 3 Test results for WEEE 1 enzyme inhibitory activity and cellular inhibitory activity Composite number WEE1 IC50, nM Composite number WEE1 ICso, nM Control 1 2.57 Control 2 1.98 1-1-1 1.90 1-1-2 2.08 I-2 2.57 1-3-1 0.35 I-3- 2 0.66 I-5 7.15 I-6 6.76 I-7 6.53 I-8 1.52 1-8-1 1.52 I-8-2 3.52 1-15-1 1.52 1- 15-2 1.68 1-17 4.05 1-19 3.89 I-20 3.45 I-23 0.71 1-31 2.05 I-32 7.39 I-33 4.22 I-34 3.30 I-36-2 2.92 I-37 1.99 i-38 1.68 I-39 2.08 I-40 4.58 1-41-1 2.11 1-41-2 2.74 IVIA / t / ZUZZ / U I0400 116 Conclusion: As shown in Table 3, the compounds of the present disclosure have a good inhibitory effect on Wee1 kinase. Effect Embodiment 2 Live btodispomMity test in mice / . Experimental animals and test products 1. Experimental animal Species Strain Certificate number Weight (grams) Number (pcs) Mice ICR 20180006002806 20 60 All of the above were provided by Shanghai Sino-British SIPPR Lab. Animal Ltd. 2. Preparation of test products 2.1 Preparation of mother liquor 404.6 uL of DMSO was added to the powder of the compound of the present disclosure until the compound was completely dissolved and 50 mg / mL of mother liquor was prepared in a clarified state. 2.2 Preparation of the administration solution The compound of the present disclosure: 24 uL of mother liquor was accurately measured, diluted to 4 ml according to the ratio of 0.9% normal saline: PEG400 = 8: 2, the concentration of the preparation was 0. 3 mg / mL, the solution was in a clarified state and was used as an intravenous administration solution. Furthermore, 80 pL of the mother liquor was accurately measured and 0.5% CIMC-Na was added to 8 ml to grind it into a uniform suspension with a concentration of 0.5 mg / mL, which was used as an intragastric administration solution. . / / . Animal experiments Intravenous group: To 24 ICR mice, 20 ± 2 g, the intravenous administration solution of the compound of the present disclosure was administered by intravenous injection, with the volume of 10 mL / kg, with the dose of 3 mg / kg. Blood was drawn from the fundus venous plexus of mice, 2, 5, 15, 30, 60, 90, 120, 240, 360, 480, 600 and 1440 minutes before and after administration. Intragastric group: 24 ICR mice, 20 ± 2 g, were administered the intragastric administration solution of the compound of the present disclosure by intragastric injection, with the volume of 20mL / kg, with the dose of 10 mg / kg, blood was extracted from! fundus venous plexus of mice, 5, 15, 30, 60, 90,120, 240, 360, 480, 600 and 1440 minutes before and after administration. The blood sample was centrifuged at 8000 rpm for 5 min and the plasma was stored in a centrifuge tube at -20” C for later use. III. Treatment of plasma samples 111 1. Standard curve preparation The concentration range of the standard working solution was 60, 20, 6, 2, 0.6, 0.2, 0.1, 0.04, pg / mL. 47.5 pL of blank mouse plasma was taken and 2.5 μΐ of standard curve working solution was added to prepare samples with a series of concentrations of 3, 1, 0.3, 0.1, 0.03, 0.01 , 0.005, 0.002 and 0.001 g / mL; The samples were vortexed evenly, and 300 pL of acetonitrile containing internal standard (propranolol, 25 ng / mL) to precipitate the protein, the samples were vortexed for 10 min, 6000 g, 40C, centrifuged for 10 min and the supernatant was injected into a 96-well plate. 2. Treatment of quality control sample The concentration range of the quality control working solution: Low: 0.06 pg / mL; Medium: 1.6 pg / mL; High: 48 .ng / mL. 47.5 pL of blank mouse plasma was taken and 2.5 pL of working solution QC was added to prepare samples with a series of concentrations of 2.4, 0.08, 0.003 pg / mL; The samples were vortexed evenly, and 300 pL of acetonitrile containing internal standard (propranolol, 25 ng / mL) to precipitate the protein, the samples were vortexed for 10 min, 6000 g, 4 “C, centrifuged for 10 min and the supernatant was injected into a 96-well plate. 3. Treatment of plasma samples 300 pL of acetonitrile containing internal standard (propranolol, 25 ng / ml) was added to 50 pL of plasma samples to precipitate proteins, shaken for 10 min, 6000 g, 4 °C, centrifuged for 10 min; The supernatant was taken before intravenous injection for 1 hour, diluted 10 times with acetonitrile containing internal standard, the rest of the supernatant was kept undiluted, centrifuged again for 10 min at 6000 g, 40C, and the supernatant was taken and then injected into a 96-well plate. / V. Experimental bioavailability results in mice 1. Test parameters Dose; maximum concentration: Cmax; Peak hour: Tmax; area under the drug-time curve of AUCuítinw 0 at time t; half-life: Ti / 2; mean retention time: MRT; clarification: Cl; apparent volume of distribution: Vz; volume distributed in steady state: Vss; absolute bioavailability: F. 2. Pharmacokinetic data from mice The pharmacokinetic parameters of the compound in mice after intravenous injection or intragastric administration are shown in Table 4 and Table 5 below. 112 MA / t / ZUZZ / UI0400 Table 4 Pharmacokinetic parameters of compounds in mice 5 Control 1 (MK1775) Control 2 1-1-1 I-8 iv po iv po iv po iv PO Dose mg / kg 3 10 3 10 3 10 3 10 Cmax ng / mL 773.8 ± 53.79 205.2 ± 124.5 646.40 ± 76.85 27.79 ± 4.76 700.8 ± 142.5 245.2 + 220.3 644.0 ± 132.2 58.08 ±7.09 10 Tmax h 0.05 ± 0.03 0.33 ± 0.14 0.03 1.67 ± 2.02 0 .03 2.50 ± 1.32 0.03 1.67 ± 0.29 AUCuitime (h) * (ng / mL) 273.1 ± 21.34 151.7 + 62.14 261.52 ± 26.93 80.15 ±9.62 372.5 ± 24.38 528.6 ± 331.1 317.5 ± 34.41 637.9 ± 302.3 Ti / 2 h 0.65 ± 0.03 3.10 ± 0.22 1.37 ± 0.33 2.51 ± 1.85 4.31 ± 1.51 3. 10 ± 9.02 1.22 ± 0.10 1.57 ± 0.39 15 MRT h 0.42 + 0.02 4.33 ± 0.28 0.86 ± 0.16 3.78 ± 1.56 1.75 ± 0.46 4.33 ± 9.02 1.11 ± 0.08 3.47 ± 1.22 Cl L / kg * h 10.99 ±0.87 / 11.3 ± 1.20 ! 7.74 ± 0.36 / 9.29 ± 0.85 i 20 Vz L / kg 10.31 ±1.12 i 22.2 ± 3.29 i 48.52 ± 18.38 / 16.33 ±2.48 / Vss L / kg 4.58 ± 0.44 / 9.69 ± 0.96 ! 13.61 ±3.95 / 10.32 ±0.86 ! F % 16.67 9.19 42.57 60.27 Table 5 Pharmacokinetic parameters of compounds in iv po mice Dose mg / kg 3 10 30 Cmax ng / mL 644.0 ± 132.2 58.08 ± 7.09 T max h 0.03 1.67 ±0.29 AUCultimate (h) * (ng / mL) 317.5 + 34.41 637.9 + 302.3 35 T1 / 2 h 1.22 + 0.10 1.57 + 0.39 113 MRT h 1.11 ±0.08 3.47 ± 1.22 Ci L / kg * h 9.29 ± 0.85 / Vz L / kg 16.33 ±2.48 / Vss L / kg 10.32 ±0.86 / F % 60.27 Conclusion: The compound of the present disclosure can significantly improve the pharmacokinetics of mice. Effect Embodiment 3 Live bioavailability test in cynomolgus monkey / . Animals and experimental subjects Twelve non-naïve male cynomolgus monkeys were acquired from GuangxiGuidong Primate Development Experiment Co. LTD. Grouping Subjects Number Dose Administration concentration Administration volume Administration mode Sample collection Male (mg / kg) (mg / mL) (ml / kg) 1 I-8-1 3 3 1.5 2 IV Plasma 2 3 20 4 5 PO * Plasma 3 AZD1 3 3 1.5 2 IV Plasma 4 775 3 20 4 5 PO * Plasma Note: * indicates oral fasting, with food removed from 16:00-17:00 p.m. the day before administration, and food was added approximately 4 hours after administration on the morning of administration. II. Subject Preparation The test product was prepared with a free alkali concentration and the purity was not converted. / / / . Preparation of the administration solution. I. Preparation of 1-8-1: 54.31 mg of 1-8-1 was accurately weighed and 1.08 ml of DIVISO was added, then the mixture was vertexed for 1 minute, sonicated for 15 minutes and then diluted to 36 ml according to the proportion of 10% ΗΡ-β cyclodextrin (prepared with normal saline): PEG = 8:2, vertex shaken for 1 min. A colorless clarified administration solution (pH value was about 7) was prepared at a concentration of 1.5 mg / ml for intravenous administration a! Group 1. 300.9 mg of 1-8-1 were accurately weighed and 75 ml of 0.5% CMC-Na were added, 114 the mixture was completely crushed and stirred for 5 min. A white suspension (pH value was about 7) was prepared at a concentration of 4 mg / ml for oral administration to Group 2. 2. Preparation of AZD1775: 54.05 mg of AZD1775 was accurately weighed and 1.08 mL of DMSO was added, then the mixture was vortexed for 1 min, sonicated for 15 min, and then diluted to 36 mL according to the ratio of β-cyclodextrin ai 10 % (prepared by normal saline): PEG = 8:2, vortexed for 1 min. A clarified yellow administration solution (pH value was about 7) was prepared at a concentration of 1.5 mg / ml for intravenous administration to Group 3. 300.7 mg of AZD1775 was accurately weighed and 75 ml of 0.5% CMC-Na was added, the mixture was completely ground and stirred for 5 min. A yellow suspension (pH value was about 7) was prepared at a concentration of 4 mg / ml for oral administration to Group 4. IV. Animal experiments 1. Dosage and method of administration. Prior to administration, all animals were fasted overnight (approximately 12 hours) and fed as needed and administered according to the table below. Grouping Gender Subjects Weight (kilogram) Subject dose 0 (mg / kg) Subject solution concentration * (mg / ml) Administration volume (ml / kg) Two is (mi) Administration route 1 M I -8-1 2.30 3 1.5 2 4.6 IV 1 M 1-8-1 2.30 3 1.5 2 4.6 IV 1 M I-8-1 2.45 3 1.5 2 5.0 IV 2 M 1- 8-1 2.50 20 4 5 13 PO 2 M 1-8-1 2.85 20 4 5 14 PO 2 M 1-8-1 2.45 20 4 5 12 PO 3 M AZD17 75 2.35 3 1.5 2 4.8 IV 3 M AZD17 75 2.55 3 1.5 2 5.2 IV 3 M AZD17 75 2.35 3 1.5 2 4.8 IV 4 M AZD17 75 2.20 20 4 5 11 PO 4 M AZD17 75 2 .30 20 4 5 12 PO 4 M AZD17 75 2.50 20 4 5 13 PO 115 * Drug concentration was calculated based on free base. “All animals were fasted overnight before administration (removed at approximately 16:00-17:00 pm the day before administration) and fed 4 hours after administration in the morning of the day. of the administration. 2. Collection and treatment of plasma samples Intravenous group: before administration (0 hr), 0.033 hr, 0.083 hr, 0.25 hr, 0.5 hr, 1 hr, 1.5 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr , 24 h after administration. Oral group: before administration (0 h), 0.083 h, 0.25 h, 0.5 h, 1.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h after administration. Blood samples were collected by puncture through lower extremity vein or other appropriate blood vessels at 1 ml / time point (3 ml of blood samples were collected from each animal before administration), anticoagulated with sodium heparin and placed on ice after collection. Plasma was separated at 2200 g / min, 10 min, 2-8°C, plasma samples were stored in a refrigerator at -80°C before being transferred to the client. Plasma samples are stored on dry ice and transferred to the client. The final treatment of the sample will be recorded in the experimental record. V. Treatment of plasma samples I. Preparation of the standard curve The concentration range of the standard working solution was 60, 20, 6, 2, 0.6, 0.2, 0.1, 0.04, 0.02 pg / mL, 47.5 pL of blank cynomolgus monkey plasma was taken and 2.5 pL of standard curve working solution was added to prepare samples with a series of concentrations of 3, 1, 0.3, 0.1, 0.03, 0.01, 0.005, 0.002 and 0.001 g / mL; The samples were vortexed evenly, and 300 pL of acetonitrile containing internal standard (Prapranolol, 25 ng / mL) was added to precipitate the protein, the samples were vortexed at 6000 g, centrifuged for 10 min. 80 pL of supernatant was injected into a 96-well plate. 2. Treatment of quality control sample The concentration range of quality control working fluid: Low: 0.06 pg / mL; Medium: 1.6 pg / mL; High: 48pg / mL. 47.5 pL of blank cynomolgus monkey plasma was taken and 2.5 pL of standard curve working solution was added to prepare samples with a series of concentrations of 2.4, 0.08, and 0.003 pg / mL; The samples were vortexed evenly, and 300 μL of acetonitrile containing internal standard (Prapranolol, 25 ng / mL) was added, the samples were vortexed at 6000 g, centrifuged for 10 min. 80 pL of supernatant was injected into IVIA / t / ZUZZ / U I0400 116 a 96-well plate. 3. Treatment of plasma samples 300 llL of acetonitrile was added to 50 μί of plasma samples containing internal standard (PropranoIoL 25 ng / mL) to precipitate proteins, vortexed for 10 min, centrifuged at 6000 g for 10 min, after the injection group intravenous I-81&AZD1775 was diluted 10 times with internal standard acetonitrile (Propranolo!, 25 ng / ml) at the time point before 1 hour, the remaining supernatant was not diluted, centrifuged again at 6000 g at 4oC for 10 min, and The supernatant was taken and injected into a 96-well plate, SAW. Experimental results of bioavailability in cynomolgus monkeys 1. Test parameters Dose; maximum concentration: Cmax; Peak hour: Tmax; area under the drug-time curve of AUCuiaro 0 at time t; half-life: Ti / 2; mean retention time: MRT; clarification: Cl; apparent volume of distribution: Vz; volume distributed in steady state: Vss; absolute bioavailability: F. 2. Pharmacokinetic data The pharmacokinetic parameters of the compound in cynomolgus monkeys after intravenous injection or intragastric administration are shown in Table 6 below. IVIA / t / ZUZZ / U I0400 Table 6 Pharmacokinetic parameters of compounds in cynomolgus monkeys Parameters AZD1775-ÍV AZD1775- 1-8-1-iv 1-8-1 -po Dose mg / kg 3 20 3 20 Gmax ng / mL 1202 ± 134 2 1627. ± 943 7 838.4 + 190.0 720.8 ± 260, 4 25 T max h 2.69 + 4.60 2.00 0.03 4.50 ± 2.60 AUCultima (h) * (ng / mL) 4494 ± 1719 8155 ± R1R 2 957.6 ± 126.3 6548 ± 3043 AUCextra (h) * (ng / mL) 47.62 ± 58 1R 8.46 ± 1.91 16.11 ±9.34 187.03 ± 166 00 AUCtot (h) * (ng / mL) 4542 ± 1777 8163 + R19 7 973.8 ±131.4 6735 ± 3201 Tmean h 2.78 + 0 .26 2.03 ±1.22 2.05 ± 1.24 3.71 + 0.72 30 MRT h 6.53 ± 2.51 3.58 ±0.07 3.17 + 0.82 7.91 + 2.00 Rinse L / h / kg 0.72 ± 0.23 / 3.12 + 0.43 / i Vz L / kg 2.84 + 0.76 / 8.78 + 4.22 / Vss L / kg 4.33 + 0.74 / 9.67 ± 1.32 í ! 35 BA % 27.22 102.56 Conclusion: The compound of the present disclosure can significantly improve 117 the pharmacokinetics of cynomolgus monkeys. Although specific embodiments of the present disclosure have been described above, those skilled in the art should understand that these are only examples, various changes or modifications can be made to these embodiments without departing from them! principle and essence of the present invention. Therefore, the scope of protection of the present disclosure is defined by the appended claims.
Claims
1. A pyrazolopyrimidine compound represented by formula II, a pharmaceutically acceptable salt thereof, a solvate thereof, a solvate of the pharmaceutically acceptable salt thereof, a metabolite thereof, or a prodrug thereof: HN N characterized in that, A is C3-C20 cycloalkyl substituted with one or two R1s; X is CH or N; R1 is independently halogen, -O1'1, -SR1'2, -CN, -NR^R14, -C(= O)R15, C^NR^R1-7, = NO-R13 or “C2-C7 alkenyl, C2-C8 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Cs-C10 aryl or C1-C7 heteroaryl” optionally substituted with one, two, or three R18s;RM is independently C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Cs-C1 arito or C1-C7 heteroaryl; R1'1'1 is independently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Ce-Cw arito, C1-C7 heteroaryl or amino substituted with one or two Ri-iii”; ries independently C1-C7 alkyl or C3-C14 cycloalkyl; R1'2 is independently hydrogen or C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Ce-Cw aryl or C1-C7 heteroaryl” optionally substituted with one, two or three R1'2·1;R1'2'1 is independently hydrogen, halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, CrC7 alkoxy, CrC7 alkylthio, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Cg-Cw aryl, C1-C7 heteroaryl or amino substituted with one or two R1'2' 1·1; Ri-2-1-1 is independently C1-C7 alkyl or C3-C14 cycloalkyl; ri-3 and ri-4 are independently hydrogen, -3(= O)2R1·3'1, -C^OJR1'3·2, -C(=NR1'3·3) 119 NR1-3-5R1-3·®, -S(=O)2NR1-3-7R1·3 8, -C(=O) NR'^R1·3·10 or C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Cs-Cw aryl or Ci-C7 heteroaryl” optionally substituted with one, two or three R1'8'11; or, R1'3 and R14 together with the nitrogen atom join to form a C3-C14 heterocycloalkyl optionally substituted with one, two or three R1'3'12;one or more methylenes in the C3-C14 heterocycloalkyl are optionally and independently substituted with an oxygen atom, a sulfur atom, sulfinyl, suifoniium, carbonyl, vinylidene or -N (R1·3'13)-; R1-3^3 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1·3'1 and ri-3-2 are independently C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl or C6-C14 aryl optionally substituted with one or two rl3-ii; Ri-3-ii is independently C1-C7 alkyl or C3-C14 cycloalkyl; R133 is independently hydrogen, -CN, C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl or C3-C14 cycloalkyl; R1·3·5, R1'3'6, R1'3·7, R1'3·8, R1'3'9 and R1'3'10 are independently hydrogen, C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl or C3-C14 cycloalkyl: or, R1'3'5 and R1-3·6 together with the nitrogen atom join to form a C3-C14 heterocycloalkyl optionally substituted with one, two or three R1-3 5-1;one or more methylene groups in the C3-C14 heterocycloalkyl are optionally and independently substituted with an oxygen atom, a sulfur atom, sulfinyl, suifoniium, carbonyl, vinylidene or -NIR1'3'5·2)-; R1-3-5-1 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1-3·5-2 is independently C1-C7 alkyl or C3-C14 cycloalkyl; or, R1'3'7 and R1'3'8 together with the nitrogen atom join to form a C3-C14 heterocycloalkyl optionally substituted with one, two or three Ri-3-7-i; one or more methylenes in the C3-C14 heterocycloalkyl are optionally and independently substituted with an oxygen atom, a sulfur atom, sulfinyl, suifoniium, carbonyl, vinylidene or -N (R'-3-7-2)-; R'-3-?-1 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R13·?·' is independently C1-C7 alkyl or C3-C14 cycloalkyl; or, R1'3'9 and R'-3'10 together with the nitrogen atom join to form a C3-C14 heterocycloalkyl optionally substituted with one, two or three R1-3 9-1;one or more methylenes in the C3-C14 heterocycloalkyl are optionally and independently substituted with an oxygen atom, a sulfur atom, sulfinyl, suifoniium, carbonyl, vinylidene or -N (R1·3'9'2)-; R1'3'®·1 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1·3 -1-2 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1'3'11 is independently halogen, hydroxy, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylithium, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Ce-Cio aryl, C1-C7 heteroaryl or amino substituted with one or two r1-3 ”-1”; r1IVIA / t / ZUZZ / U I0400 120 3-114 is independently C1-C7 alkyl or C3-C14 cycloalkyl;R1'3'12 is independently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Cg-Cw aryl, C1-C7 heteroaryl or amino substituted with one or two R1· 3-12-1 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1'5 is independently hydrogen, -NR'-'-'R1'5^, -O'-5'3 or C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Cg-Cw aryl or C1-C7 heteroaryl” optionally substituted with one, two or three R1'5'4; ρΐ·5-ι and Ri-5-2 are independently hydrogen, C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl or C3-C14 cycloalkyl; or, R1'5'1 and R1'5'2 together with the nitrogen atom join to form a C3-C14 heterocycloalkyl optionally substituted with one, two or three Ri-s ^i;one or more methienes in the C3-C14 heterocycloalkyl are optionally and independently substituted with an oxygen atom, a sulfur atom, sulfinyl, sulfonyl, carbonyl, vinylidene or -N (R1-5-1·2)-; R1'5'1'1 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R15·1·2 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1'5'3 is independently hydrogen, C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Cg-Cw aryl or C1-C7 heteroaryl; R1'54 is independently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Cg-Cw aryl, C1-C7 heteroaryl or amino substituted with one or two R1'5·4'1”; R15·4'1 is independently C1-C7 alkyl or C3-C14 cycloalkyl;R1S is independently hydrogen, -CN, -OH or C1-C7 alkyl, C2-C7 alkenyl, C2C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Cg-Cw aryl or C1-C7 heteroaryl” optionally substituted with one, two or three R1'®'1; R1·®·4 is independently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C6-C10 aryl, C1-C7 heteroaryl or ''amino substituted with one or two r1-®-'-1”; R16'1·1 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1'7 is independently hydrogen, -OR1'7'1, -NR1'7'2R1'7'3 or C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Cg-Cw aryl or C1-C7 heteroaryl” optionally substituted with one, two or three R77 R R1'7'1 is independently hydrogen, C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Cg-Cw aryl or C1-C7 heteroaryl;and ri-7-3 are independently C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl or C3-C14 cycloalkyl; 121 or, R1'7'2 and R1'7'3 together with the nitrogen atom join to form a C3-C14 heterocycloalkyl optionally substituted with one, two or three R1-7 2-1; one or more methylenes in the C3-Cu heterocycloalkyl are optionally and independently substituted with an oxygen atom, a sulfur atom, sulfinyl, sulfoniium, carbonyl, vinylidene or -N (R17·2·2)-; R1·7·2·1 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1'7·2'2 is independently C1-C7 alkyl or C3-C14 cidoalkyl; R1-7-4 is independently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Ce-Cio arito, C1-C7 heteroaryl or amino substituted with one or two Ri-7-4-i”; R1· 10 7-4-1 is independently CrC? alkyl or C3-C14 cycloalkyl;R1'8 is independently oxo, halogen, -OH, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C6-C1 aryl, C1-C7 heteroaryl, or amino substituted with one or two R1'8·1”; R1S' 1 is independently C1-C7 alkyl or C3-C14 cidoalkyl; R19 is independently hydrogen or C1-C7 alkyl; R2 is -O2-1, cyano, carboxyl; or C2-C7 alkyl, C3-C14 cycloalkyl, or C3-C14 heterocycloalkyl optionally substituted with one, two, or three R2'2; R2'1 is C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 alkyl acido, C3-C14 heterocycloalkyl, C6-C10 aryl or C1-C7 heteroaryl; 20 R2'2 is independently halogen, hydroxyl, amino, C1-C7 alkyl, C1-C16 alkoxy, C3-C14 cycloalkyl or C3-C14 heterocycloalkyl;In any of the above cases, the heteroatoms in the C3-C14 heterocycloalkyl, C1-C7 heteroaryls are independently selected from one or more of boron, silicon, oxygen, sulfur, selenium, nitrogen, and phosphorus; the number of heteroatoms is independently 1, 2, 3, 25, or 4.
2. The pyrazolopyrimidine compound represented by formula II according to claim 1, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof or the prodrug thereof, characterized in that the compound is a pyrazolopyrimidine compound represented by formula I: ΊΛ / t / ZUZZ / U I0400 122 where, A is a C3-C20 cycloalkyl substituted with one or two R1; R1 is independently halogen, -O1-1, -SR12, -CN, -NR'^R1'4, -C^OjR1-5, -C(=NR1' 6) R1'7 or C2-C7 alkenyl, C2-Cs alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C6-C10 aryl or C1-C7 heteroaryl” optionally substituted with one, two or three R18; R1'1 is independently “C1-C7 alkyl, C2-C7 akenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C6-C10 aryl or C1-C7 heteroaryl optionally substituted with one, two or three R1'1'1;R1'1'1 is independently halogen, hydroxy, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C2-C7 alkenyl, C2-C1 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C6-C1w aryl, C1-C7 heteroaryl or amino substituted with one or two Ri-iii”; R1^-1 is independently C1-C7 alkyl or C3-C1 “cycloalkyl”; R1'2 is independently hydrogen, or C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C6-C1w aryl or C1-C7 heteroaryl” optionally substituted with one, two or three R1'2'1; R1·21 is independently hydrogen, halogen, hydroxy, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Cs-C10 aryl, C1-C7 heteroaryl or amino substituted with one or two R1'2' 1-1»; it is independently C1-C7 alkyl or C3-C14 cycloalkyl;Ri-s and Ri-4 are independently hydrogen, -S(=O)2R1·3'1, -C (=O)R1'3'2, -C(=NR1'3· ^NR^^R1'3'8, -S(= O)2NR1'3'7R'·3·8, -C^OJNR1-^^-3·10 or C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, Cs-Cm heterocycloalkyl, Ce-Cio aryl or C1-C7 heteroaryl” optionally substituted with one, two or three RV3-11; or, R13 and R1'4 together with the nitrogen atom join to form a C3-C14 heterocycloalkyl optionally substituted with one, two or three R1'3'12; one or more methylenes in the C3-C14 heterocycloalkyl are optionally and independently substituted with an oxygen atom, a sulfur atom, sulfinyl, sulfonyl, carbonyl, vinylidene or -N (R: 813)-, R13 ·3 is independently C1-C7 alkyl or C3-C14 cycloalkyl; Ri-3-1 and Ri-3-2 are independently C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl or Ce-Cio aryl optionally substituted with one or two R1-3-1^;r'-3-ii is independently C1-C7 alkyl or C3-C14 cycioalkyl; R1'3'3 is independently hydrogen, -CN, C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl or C3-C14 cycioalkyl; R138, R1-3-6, R1-3'7, R1-3'8, R1'3'9 and R1-'3'10 are independently C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl or C3-C14 cycioalkyl; or, R1-3'5 and R1-3'® together with the nitrogen atom join to form a C3-C14 heterocycloalkyl optionally substituted with one, two or three R13 5 one or more methylenes in 123 the C3-C14 heterocycloalkyl are optionally and independently substituted with an oxygen atom, a sulfur atom, sulfinite, sulfonyl, carbonite, vinylidene or -N(R1'3·5·2)-; R1-3'5-1 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1-3-5-2 is independently C1-C7 alkyl or C3-C14 cycloalkyl; or, Rá3'7 and R1-3-8 together with the nitrogen atom join to form a C3-C14 alkyl heteroacid optionally substituted with one, two or three r1-3 7-1;one or more methiene groups in the C3-C14 alkyl heteroacid are optionally and independently substituted with an oxygen atom, a sulfur atom, sulfinyl, sulfonyl, carbonite, vinylidene or -NCR1'3'7'2)-; R1-3-71 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1-3·7-2 is independently C1-C7 alkyl or C3-C14 cycloalkyl; or, R1479 and R1-3-13 together with the nitrogen atom join to form a C3-C14 alkyl heteroacid optionally substituted with one, two or three Ri-39-i; One or more methiene groups in the C3-C14 alkyl heteroside are optionally and independently substituted with an oxygen atom, a sulfur atom, sulfinyl, sulfonyl, carbonite, vinylidene or -N / R1'3'9'2)-; R'-3-9-1 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R13·9·2 is independently C1-C7 alkyl or C3-C14 cycloalkyl;R^-n is independently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C2-C7 alkenite, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C2-C10 anta, C1-C7 heteroaryl or amino substituted with one or two ri-3-”-’”; r1 is independently C1-C7 alkyl or C3-C14 cycloalkyl; Rf-3-12 is independently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C2-C7 alkenite, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heteroalkyl, C6-C10 aryl, C1-C7 heteroaryl or amino substituted with one or two RJ·3^2 '”; ri3'12'1 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1'5 is independently hydrogen, -NR^R'·5·2, -O1'5'3 or “C1-C7 alkyl, C2-C7 alkenite, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heteroalkyl, C6-C <o arilo o C1-C7 heteroarilo opcionalmente sustituido con uno, dos o tres R1’5'4;Ri-5-1 and Ri-5-2 are independently hydrogen, C1-C7 alkyl, C2-C7 alkenite, C2-C7 alkynyl, or C3-C14 cycloalkyl; or, R1'51 and R1'5'2 together with the nitrogen atom join to form a C3-C14 alkyl heteroacid optionally substituted with one, two, or three R1-51-1; one or more methienes in the C3-C14 alkyl heteroacid are optionally and independently substituted with an oxygen atom, a sulfur atom, sulfinyl, sulfonyl, carbonite, vinylidene, or -NCR1·5'1'2)-; R1'5'1'1 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1·5·1·2 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R15 3 is independently hydrogen, C1-C7 alkyl, C2-C7 alkenite, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Cs-C™ aryl or C1-C7 heteroaryl;ri-5-4 is independently halogen, hydroxyl, amino, mercapto, cyanide, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C2-C7 alkenium, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C6-C1Q aryl, C1-C7 heteroaryl or amino substituted with one or two Ri 5 41”; R1· 544 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1’8 is independently hydrogen, -CN, -OH or C1-C7 alkyl, C2-C7 alkenium, C2C7 alkynyl, C3-C1 cycloalkyl, C3-C14 heterocycloalkyl, Ce-C1 aryl or C1-C7 heteroaryl” optionally substituted with one, two or three R1-64; R1-34 is independently halogen, hydroxy, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C2-C7 alkenium, C2-Cr alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C2-C10 aryl, C1-C7 heteroaryl or amino substituted with one or two R1-644”; R1-644 is independently C1-C7 alkyl or C3-C14 cycloalkyl;R1'7 is independently hydrogen, -OR1 7'1, -NR^^R1'7'3 or C1-C7 alkyl, C2-C7 alkenium, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C5-C10 aryl or C1-C7 heteroaryl” optionally substituted with one, two or three R'-7'4; R1'74 is independently hydrogen, C1-C7 alkyl, C2-C7 alkenium, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C5-C10 aryl or C1-C7 heteroaryl; Ri-7-2 and Ri-7-3 are independently C1-C7 alkyl, C2-C7 alkenium, C2-C7 alkynyl or C3-C14 cycloalkyl; or, R17'2 and R'73 together with the nitrogen atom join to form a C3-Ci4 heterocycloalkyl optionally substituted with one, two or three R1-7·24; one or more methylenes in the C3-Ci4 heterocycloalkyl are optionally and independently substituted with an oxygen atom, a sulfur atom, sulfinite, sulfoniium, carbonyl, vinylidene or -N(R1'7'2 2)-; R1·72·1 is independently C1-C7 alkyl or C3-Ci4 cycloalkyl;R1-7-2-2 is independently C1-C7 alkyl or C3-C14 cytoalkyl; R1·74 is independently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C2-C7 alkenium, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C6-C10 aryl, C1-C7 heteroaryl or amino substituted with one or two R1'744”; R17'4·1 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1'8 is independently halogen, -OH, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C2-C7 alkenium, C2-C1 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Ce-C1 aryl, C1-C7 heteroaryl or amino substituted with one or two R1-84”; R1-81 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R2 is -O24, cyano, carboxyl; or C2-C7 alkyl, C3-C14 cycloalkyl or C3-C14 heterocycloalkyl” optionally substituted with one, two or three PL2;R24 is C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C6-C10 aryl or C1-C7 heteroaryl; R2'2 is independently halogen, hydroxyl, amino, C3-C17 alkyl, C1-C17 alkoxy, C3-C14 cycloalkyl or C3-C14 heterocycloalkyl; in any of the above cases, the heteroatoms in the C3-C14 heterocycloalkyl, the C3-C14 heteroatoms, are independently selected from one or more of boron, silicon, oxygen, sulfur, selenium, nitrogen and phosphorus; the number of heteroatoms is independently 1, 2, 3 or 4.
3. The pyrazolopyrimidine compound represented by formula II according to claim 1 or 2, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof, or the prodrug thereof, characterized in that, when A is C3-C20 cycloalkyl substituted with one or two R1s, the C3-C20 cycloalkyl is C3-C20 monocyclic cycloalkyl, C3-C20 spiro cycloalkyl, C3-C20 condensed cycloalkyl, or C3-C20 bridged cycloalkyl; and / or, when A is C3-C20 cycloalkyl substituted with one or two R1s, the C3-C20 cycloalkyl is C3-C20 saturated cycloalkyl; and / or, when R1 is independently C3-C14 heterocycloalkyl, the C3-C14 heterocycloalkyl is C3-Cu monocyclic heterocycloalkyl, C3-Ci4 spiro heterocycloalkyl, C3Cu condensed heterocycloalkyl or C3-C14 bridged heterocycloalkyl;and / or, when R1 is independently C3-C14 heterocycloalkyl, the heteroatom of the C3-C14 heterocycloalkyl is not substituted; and / or, when R· is independently C3-C14 heterocycloalkyl, the methylene in the C3Cu heterocycloalkyl is not substituted; and / or, when R1 is independently C3-C14 heterocycloalkyl substituted by an R1'8, the C3-C14 heterocycloalkyl is a monocyclic C3-C14 heterocycloalkyl, a C3-C14 spiro heterocycloalkyl, a condensed C3-Cu heterocycloalkyl, or a bridged C3-C14 heterocycloalkyl; and / or, when R1 is independently C3-C14 heterocycloalkyl substituted by an R1'8, the heteroatom of the C3-C14 heterocycloalkyl is not substituted except for R1-8; and / or, when R1 is independently C3-C14 heterocycloalkyl substituted by an Rb8, the methylene in the C3-C14 heterocycloalkyl is unsubstituted; and / or, when R1'3 and R1' are independently Ci-C7 alkyl, the C1-C7 alkyl is C1C3 alkyl;and / or, when R1'3'1 is independently Ci-C? alkyl, the C1-C7 alkyl is CrC3 alkyl; and / or, when R1'3'2 is independently C3-C14 cycloalkyl, the C3-C14 cycloalkyl is C3-C14 monocyclic cycloalkyl, C3-C14 spiro cycloalkyl, C3-C14 condensed cycloalkyl or C3C14 bridged cycloalkyl; 126 and / or, when R1'3'2 is C3-C14 cycloalkyl, the C3-Cu cycloalkyl is C3-C14 saturated cycloalkyl; and / or, when R1'5 is independently C3-C14 heterocycloalkyl, the C3-C14 heterocycloalkyl is a monocyclic C3-C14 heterocycloalkyl, a C3-C14 spiro heterocycloalkyl, a condensed C3CM heterocycloalkyl, or a bridged C3-C14 heterocycloalkyl; and / or, when R15 is independently C3-C14 heterocycloalkyl, the heteroatom of the C3-C14 heterocycloalkyl is unsubstituted; and / or, when R15 is independently C3-C14 heterocycloalkyl, the methylene group in the C3Cu heterocycloalkyl is unsubstituted;and / or, when R1'5'1 and R1-5-2 are independently CrC? alkyl, the C1-C7 alkyl is C1-C3 alkyl; and / or, when R15'1 and R1'52 are independently C3-Ci4 cycloalkyl, the C3-Ci4 cycloalkyl is C3-Ci4 monocyclic cycloalkyl, C3-C14 spiro cycloalkyl, C3-C14 condensed cycloalkyl or C3-C14 bridged cycloalkyl; and / or, when R1'5'1 and R13'2 are independently C3-C14 cycloalkyl, the C3-C14 cycloalkyl is C3-C14 saturated cycloalkyl; and / or, when R>5“3 is independently C1-C7 alkyl, the C1-C7 alkyl is C1-C3 alkyl; and / or, when R1-3 is independently C1-C7 alkyl, the C1-C7 alkyl is C1-C3 alkyl; and / or, when R2 is C2-C7 alkyl optionally substituted with one, two or three R2 2, the C2C7 alkyl is C2-C4 alkyl;and / or, when R2 is C3-C14 heterocycloalkyl optionally substituted with one, two, or three R2'2, the C3-C14 heterocycloalkyl is a C3-C14 monocyclic heterocycloalkyl, C3-C14 spiro heterocycloalkyl, condensed heterocycloalkyl, or bridged C3-C14 heterocycloalkyl; and / or, when R2 is C3-C14 heterocycloalkyl optionally substituted with one, two, or three R22, the heteroatom of the C3-C14 heterocycloalkyl is unsubstituted except for R2 2; and / or, when R2 is C3-C14 heterocycloalkyl optionally substituted with one, two, or three R2'2, the methylene in the C3-C14 heterocycloalkyl is unsubstituted; and / or, the proportion of each isomer in the pyrazolopyrimidine compound represented by formula II is equal;and / or, the atoms in the pyrazolopyrimidine compound represented by formula II, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof, or the prodrug thereof all exist in their natural abundance; 4. The pyrazolopyrimidine compound represented by formula II according to claim 3, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof, or the prodrug thereof, characterized in that, when A is C3-C20 cycloalkyl substituted with one or two R1s, the C3-C20 cycloalkyl is C3-C20 monocyclic cycloalkyl, C3-C20 monocyclic cycloalkyl is C3-C6 monocyclic cycloalkyl; and / or, when A is C3-C20 cycloalkyl substituted with one or two R1s, the C3-C20 cycloalkyl is C3-C20 bridged cycloalkyl; the C3-C20 bridged cycloalkyl is C5-C8 bridged cycloalkyl; and / or, when R1 is independently C3-C14 heterocycloalkyl, the C3-C,4 heterocycloalkyl is a C3-C14 monocyclic heterocycloalkyl; the C3-C14 monocyclic heterocycloalkyl is a C3-Cg monocyclic heterocycloalkyl having one or two heteroatoms selected from one or two of N, O and S;and / or, when R1 is independently C3-C14 heterocycloalkyl substituted by an R1-B, the C3-C14 heterocycloalkyl is a monocyclic C3-C14 heterocycloalkyl; the monocyclic C3-C14 heterocycloalkyl is the monocyclic C3-C9 heterocycloalkyl having one or two heteroatoms selected from one or two of N, O, and S; and / or, when R1'3 and R1-4 are independently C1-C7 alkyl, the C1-C7 alkyl is methyl, ethyl, n-propyl, or isopropyl; and / or, when R1'3'1 is independently C1-C7 alkyl, the C1-C7 alkyl is methyl, ethyl, n-propyl, or isopropyl; and / or, when R1'3-2 is independently C3-Ci4 cycloalkyl, the C3-Cu cycloalkyl is C3-C14 monocyclic cycloalkyl; the C3-C14 monocyclic cycloalkyl is C3-Cs monocyclic cycloalkyl; and / or, when R1'5 is independently C3-Ci4 heterocycloalkyl, the C3-C14 heterocycloalkyl is C3-C14 monocyclic heterocycloalkyl;The C3-C14 monocyclic heterocycloalkyl is a C3-C8 monocyclic heterocycloalkyl having one or two heteroatoms selected from one or two of N, O, and S; and / or, when R1'5·1 and R1'52 are independently C1-C7 alkyl, the C1-C7 alkyl is methyl, ethyl, n-propyl, or isopropyl; and / or, when RV5'1 and R1'5'2 are independently C3-Ci4 cycloalkyl, the C3-Ci4 cycloalkyl is a C3-C14 monocyclic cycloalkyl; the C3-Ci4 monocyclic cycloalkyl is a C3-C6 monocyclic cycloalkyl; and / or, when R1S'3 is independently C1-C7 alkyl, the C1-C7 alkyl is methyl, ethyl, n-propyl, or isopropyl. and / or, when R2 is C2-C7 alkyl optionally substituted with one, two or three R2-2, the C2C7 alkyl is ethyl, n-propyl, isopropyl, n-butyl, isobutyl, n-butyl or 7-butyl; and / or, when R2 is independently C3-C14 heterocycloalkyl substituted with one, two or three R22, the C3-C14 heterocycloalkyl is a C3-C14 monocyclic heterocycloalkyl;The C3-C9 monocyclic heterocycloalkyl is a C3-C9 monocyclic heterocycloalkyl having one or two heteroatoms selected from one or two of N, O, and S and / or, the proportion of each isomer in the pyrazolopyrimidine compound represented by formula I is equal; and / or, the atoms in the pyrazolopyrimidine compound represented by formula I, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof, or the prodrug thereof all exist in their natural abundance.
5. The pyrazolopyrimidine compound represented by formula II according to claim 4, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof, or the prodrug thereof, characterized in that, when A is C3-C2o cycloalkyl substituted with one or two R1s, the C3-C2o cycloalkyl is a monocyclic C3-C2o cycloalkyl, the monocyclic C3-C2o cycloalkyl is cyclopropyte, cyclobutyl, cyclopentyl, or cyclohexyl; and / or, when A is C3-C2o cycloalkyl substituted with one or two R1s, the C3-C2o cycloalkyl is a bridged C3-C2o cycloalkyl; the bridged C3-C2a cycloalkyl is δεικ ... is independently C3-C14 heterocycloalkyl, the C3-C14 heterocycloalkyl is C3-C14 monocyclic heterocycloalkyl; the C3-C14 heterocycloalkyl and / or, when R1 is independently C3-Cu heterocycloalkyl substituted by an Rb6, Γ )=O the C3-C14 heterocycloalkyl substituted by an R1'8 is ;and / or, when R1'3'2 is C3-C14 cycloalkyl, the C3-C14 cycloalkyl is a C3-C14 monocyclic cycloalkyl; the C3-C14 monocyclic cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; and / or, when R15 is independently C3-C14 heterocycloalkyl, the C3-C14 heterocycloalkyl is a C3-C14 monocyclic heterocycloalkyl; the C3-C14 monocyclic heterocycloalkyl is ; and / or, when R1'5' and R, ü'2 are independently C3-C14 cycloalkyl, the C3-C14 cycloalkyl is a C3-C14 monocyclic cycloalkyl; the C3-C14 monocyclic cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; and / or, when R2 is a C3-C14 heterocycloalkyl optionally substituted with one, two or three R22, the C3-C14 heterocycloalkyl is a C3-C14 monocyclic heterocycloalkyl; the C3-C14 monocyclic heterocycloalkyl is oxethan-3-yl.; 6. The pyrazolopyrimidine compound represented by formula II according to claim 1 or 2, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof, or the prodrug thereof, characterized in that, when A is a C3-C20 cycloalkyl substituted by an R1, A is R1 or R1; and / or, when R1 is independently a C3-C14 heterocycloalkyl, the C3-C14 heterocycloalkyl is a monocyclic C3-C14 heterocycloalkyl; the C3-C14 heterocycloalkyl and / or, when R1 is independently a C3-C14 heterocycloalkyl, the C3-C14 heterocycloalkyl is a monocyclic C3-C14 heterocycloalkyl; the monocyclic C3-C14 heterocycloalkyl is λ; and / or, when R2 is a C2-C7 alkyl substituted by an R2'2, R2'2 is hydroxyl; the C2-C7 alkyl OH substituted by an R2'2 is i; and / or, when R2 is a C3-Cu heterocycloalkyl substituted by an R2-2, R2'2 is a halogen or I—O hydroxyl;The C3-C14 heterocycloalkyl substituted by an R2'2 is OH or F; 7. The pyrazolopyrimidine compound represented by formula II according to claim 6, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof, or the prodrug thereof, characterized in that, where A is C3-C2o cycloalkyl substituted by an R1; A is R1 8. The pyrazolopyrimidine compound represented by formula II according to claim 1 or 2, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof or the prodrug thereof, characterized in that A is a C3-C20 cycloalkyl substituted by an R1; and / or X is N; and / or, R1 is independently cyano, halogen, -NR1'3R1'4, -C(=O)R1'5, -C(=NR1'6)R1'7, 15 = NO-R1'9, C1-C7 heteroalkyl or C3O14 heterocycloalkyl” optionally substituted with an R1“8; and / or, R^ and R1'4 are independently hydrogen, -S(=O)2R1·3·1, -C(=O) R1'3'2, -CÁNR1' ^NR1·3·^1·3·6, or C1-C7 alkyl; R1'3'1 and R! 3 2 are independently C1-C7 alkyl or C3-C14 cycloalkyl; R1'3'3 is hydrogen; R1'3'5 and R1-3 6 are hydrogen; and / or, R15 is independently -^1-54^2.-O1'5'3 or C3-C14 heterocycloalkyl; R1·5'1 and R1'5'2 20 are independently hydrogen, C1-C7 alkyl or C3-C14 cycloalkyl; R15'3 is independently hydrogen or C1-C7 alkyl; and / or, R1'8 is independently oxo; and / or, Rz is C2-C7 alkyl, C3-C14 cycloalkyl or C3-C14 heterocycloalkyl optionally substituted with one, two or three R2'2; R2'2 is independently halogen or hydroxyl.
25.
9. The pyrazolopyrimidine compound represented by formula II according to claim 1 or 2, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof, or the prodrug thereof, characterized in that A is a C3-C20 cycloalkyl substituted by an R1; and / or, R1 is independently cyano, halogen, -NR^R1'4, -C(=O)R1'5, -C(=NR1'S)R1'7, C3-C7 heteroalkyl, or C3-C14 heterocycloalkyl; and / or, R1'3 and R1'4 are independently hydrogen, -S^O^R1'34, or C1-C7 alkyl; R1'34 is independently C1-C7 alkyl; and / or, R1S is independently -nr^s-'R'-5-2, -O1-5'3 or C3-C14 heterocycloalkyl; R1'5'1 and R1'5'2 are independently hydrogen, C1-C7 alkyl or C3-C14 cycloalkyl; R1-5-3 is independently hydrogen or CrC? alkyl; and / or, R2 is C2-C7 alkyl, C3-C14 cycloalkyl or C3-C14 heterocycloalkyl optionally > π NC 131 substituted with one, two or three R2 2;R2 2 is independently halogen or hydroxyl.; 10. The pyrazolopyrimidine compound represented by formula II according to claim 9, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof, or the prodrug thereof, characterized in that, R1 is independently -NR1'3R1'4, -C (= O) R1'5 or C3-C14 heterocycloalkyl; and / or, R1'5 is independently -NR1·5'^1'5'2, -O1-5'3 or C3-C14 heterocycloalkyl; R1'5'1 and R1'5'2 are independently hydrogen, C1-C7 alkyl or C3-C14 cycloalkyl; R15'3 is hydrogen; and / or, R2 is C2-C7 alkyl or C3-C14 heterocycloalkyl substituted by an R22”; R2'2 is halogen or hydroxyl.
11. The pyrazolopyrimidine compound represented by formula II according to claim 1 or 2, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof or the prodrug thereof, characterized in that the pyrazolopyrimidine compound represented by formula II is any of the following schemes: Scheme 1): A is substituted by one or two R1; R1 is independently halogen, -CN, -NR^R14, -C(=O)R1'5, -C^NR^R1'7 or C3Cu cycloalkyl, C3-C14 heterocycloalkyl, Cs-Cyc aryl or C1-C7 heteroaryl” optionally substituted with one, two or three R18; R1-3 and ri-4 are independently hydrogen, -S(=O)2R1“3'1, -C(=O)R1·3'2, -C^NR1·3'3) NR1-3-sR1-3-6, -S(=O)2NR'3'7R1·38, -C(=O) NR^^R1'3'10 or C1-C7 alkyl, C3-CM cycloalkyl, C3Cu heterocycloalkyl, Ce-Cio aryl or C1-C7 heteroaryl” optionally substituted with one, two or three R1'3'11;Ri-3-1 and Ri-3-2 (or) independently “C1-C7 alkyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl or Ce-Cio aryl optionally substituted with one or two R1-· ' '· R: 2 ! í is independently C1-C7 alkyl; R1'3'3 is independently hydrogen; R1'3S, R13·6, R13'7, R1'3'8, R1'3'9 and R1'3'10 are independently C1-C7 alkyl or C3-C14 cycloalkyl; R1'3'11 is independently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Cs-C10 aryl, C1-C7 heteroaryl or amino substituted with one or two R'-snv; ^1-3-11-1 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1'5 is independently hydrogen, -NR^R1'5'2, -O1's'3 or C1-C7 alkyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C1-C10 aryl or C1-C7 heteroaryl optionally substituted with one, two or three R15'4; R1·5'1 and Ri-5-2 are independently hydrogen, C1-C7 alkyl or C3-C14 cycloalkyl;R1'5·3 is independently hydrogen, C1-C7 alkyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Cs-C10 aryl or C1-C7 heteroaryl; R154 is independently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C3-Cu cycloalkyl, C3-C14 heterocycloalkyl, C3-C10 aryl, C1-C7 heteroaryl or amino substituted with one or two Ri-s-+i'; Ri-5-4-1 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1's is independently hydrogen, -CN, -OH; R1-7 is independently hydrogen, -NR^R1-7-3; Ri-7-2 and pi-7-3 are independently C3-C14 alkyl or cycloalkyl; or, R1'7'2 and R1·7'3 together with the nitrogen atom join to form a C3-C14 heterocycloalkyl optionally substituted with one, two or three Ri-+2-i; one or more methylenes in the C3-C14 heterocycloalkyl are optionally and independently substituted with an oxygen atom, a sulfur atom; R1-7-21 is independently C1-C7 alkyl or C3-C14 cycloalkyl;R1'8 is independently halogen, -OH, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C1-C10 aryl, C1-C7 heteroaryl, or amino substituted with one or two R1'8"; R1·®·1 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R2 is C2-C7 alkyl, C3-C14 cycloalkyl, or C3-C14 heterocycloalkyl optionally substituted with one, two, or three R2'2; R2'2 is independently halogen or hydroxyl; in any of the above cases, the heteroatoms in the C3-C14 heterocycloalkyl, C3-C14 heteroaryls are independently selected from one or more of boron, silicon, oxygen, sulfur, sethenium, nitrogen and phosphorus; the number of heteroatoms is independently 1, 2, 3 or 4; scheme (2): 133 A is C3-C20 cycloalkyl substituted with one or two R1; R1 is independently cyano, halogen, -NR1'3R1'4, -C(=O)R1'5, -C1NR1'5) R1'7, C1C7 heteroaryl or C3-C14 heterocycloalkyl;Ri-3 and Ri-4 then met <j¡en|emer(^e hidrógeno, -S^O^R1’3’1 o C1-C7 alquilo; R1·3'1 es independientemente C1-C7 alquilo; R1'5 es independiente -NR^R1'5·2, -O'·5·3 o C3-C14 heterocicloalquilo; R1'5'1 y R1'5'2 son independientemente hidrógeno, C1-C7 alquilo o C3-C14 cicloalquilo; R1’5 3 es independientemente hidrógeno o C1-C7 alquilo; R2 es C2-C7 alquilo o C3-C14 heterocicloaiquilo sustituido por un R2 2; R2'2 es halógeno o hidroxilo; esquema (3): A es C3-C20 cicloalquilo sustituido por un R1; R1 es -NR^R1·4, -C^COR1'5 o C3-C14 heterocicloalquilo; R1-3 y ri-4 son independientemente hidrógeno, -S(”O)2R1·3'1 o Cr-C? alquilo; R1-3'1 es independientemente C1-C7 alquilo; R1-5 es -NR^-R1·52, -O1-5-3 o C3-C14 heterocicloalquilo; R·'5’1 y R1-5-2 son independientemente hidrógeno, C1-C7 alquilo o C3-C14 cicloalquilo; R1’5’3 es hidrógeno o C1-C7 alquilo; R2 es C2-C7 alquilo o C3-C14 heterocicloalquilo sustituido por un R2 2”; R2'2 es hidroxilo;Scheme (4): 134 A is C3-C20 cycloalkyl substituted by an R1; R1 is -NR^R1·4, -C(= O)R1-5 or C3-C14 heterocycloalkyl; R1-3 and ri-4 are independently hydrogen, -S^O^R1'3'1 or C1-C7 alkyl; R1'3'1 is independently C1-C7 alkyl; R1'5 is -NR1'5'^1'5'2, -O1-5'3 or C3-C14 heterocycloalkyl; R1'5'1 and Ru22 are independently hydrogen, C1-C7 alkyl or C3-C14 cycloalkyl; R1'5 3 is hydrogen; R2 is C2-C7 alkyl or C3-C14 heterocycloalkyl substituted by an R2 2”; R2’2 is hydroxyl; scheme (5): R1 is -NR^R1’4, -C^OjR1’5 or C3-O14 heterocycloalkyl; R1-3 and R1’4 are independently hydrogen. -S(=O)2R13·1 or C1-C7 alkyl; R1’3’1 is independently C1-C7 alkyl; R1’5 is -NR’^’R1·5·2, -O1’5’3 or C3-C14 heterocycloalkyl; R1’3’1 and R25’2 are independently hydrogen, C1-C7 alkyl or C3-C14 cycloalkyl; R1’5’3 is hydrogen or C1-C7 alkyl; R2 is C2-C7 alkyl or C3-C14 heterocycloalkyl substituted by an R2'2”; R2'2 is hydroxyl; scheme (6);A is R1 is -ΝΗ'^Η1'4, -C(=O) R75 or C3-C14 heterocycloalkyl; R1'3 and ri-4 are independently hydrogen, -S(=O)2R1“3'1 or C1-C7 alkyl; R1'3'1 is independently C1-C7 alkyl; R1'5 is -NR'^R1-5·2, -O1-5·3 or C3-C14 heterocycloalkyl; R1-51 and R15·2 are independently hydrogen, C1-C7 alkyl or C3-C14 cycloalkyl; R1'5-3 is hydrogen or C1-C7 alkyl; X is OH or N; R1 is independently halogen, -CN, -NR'-'R1'4, -C (= O) R1'5, -C (= NR! 6) R1'7, = NO-Ri eo C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Ce-Cw aryl or C1-C7 heteroaryl” optionally substituted with one, two or three R1-8; R1-3 and Ri-4 are independently hydrogen, -S(=O)2R1'3'1, -C(=O) R1'3'2, -C(=NR'·3'3) NRI-3-5RI-3-6, -S(=O)2NR1-3-7R1-3-8, -C(=O) NR^^R1'3'10 or C1-C7 alkyl, C3-C14 cycloalkyl, C3C14 heterocycloalkyl, Cr-Cio aryl or C1-C7 heteroaryl optionally substituted with one, two or three R '·3· '1;R1-3-1 and ri-3-2 are independently C1-C7 alkyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl or Ce-Cio aryl optionally substituted by one or two Ri-3-1-1; r>-3-ii is independently C1-C7 alkyl; R1-3'3 is independently hydrogen; R1'3'5, R1-3'8, R1'3'7, R1-3'8, R1-3'9 and R1-3-10 are independently hydrogen, C1-C7 alkyl or C3-C14 cycloalkyl; 136 R1'3'11 is independently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C3-Cu cycloalkyl, C3-C14 heterocycloalkyl, Ca-Cw ariio, C1-C7 heteroaryl or amino substituted with one or two R1-3-11-1 is independently C1-C7 alkyl or C3-C14 cycloalkyl; 5 R1-5 is independently hydrogen, -IMR^R1'5'2, -O1'5'3 or C1-C7 alkyl, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, C6-Ci0 ariio or C1-C7 heteroaryl optionally substituted with one, two or three R1'5'4; ρΐ-5-ι and Ri-5-2 are independently hydrogen, C1-C7 alkyl or C3-Ci4 cycloalkyl;R1·5'3 is independently hydrogen, C1-C7 alkyl, C3-C14 cycloalkyl, C3-C14 θ heterocycloalkyl, C6-Cw arylium or C1-C7 heteroaryl; R1'5'4 is independently halogen, hydroxyl, amino, mercapto, cyano, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 alkylthio, C3-C14 cycloalkyl, C3-C14 heterocycloalkyl, Cs-C10 arylium, C-C7 heteroaryl, or amino substituted with one or two rts-4-1”- R1-5-4-1 is independently C1-C7 alkyl or C3-C14 cycloalkyl; 5 R1^ is independently hydrogen, -CN, -OH; R1'7 is independently hydrogen, -NR1'7'2R1'7'3; ri-?-2 and pi-7-3 are independently C1-C7 alkyl or C3-C14 cycloalkyl; or, R1'7'2 and R1'7'3 together with the nitrogen atom join to form a C3-C14 heterocycloalkyl optionally substituted with one, two or three R1'7'2'1; one or more methylenes at ® the C3-C14 heterocycloalkyl are optionally and independently substituted with an oxygen atom, a sulfur atom;R1-7-2·1 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1'3 is independently oxo, halogen, -OH, amino, mercapto, cyano, C1-C7 alkyl, CrC? alkoxy, C1-C7 alkylthio, C3-Cu cycloalkyl, C3-C14 heterocycloalkyl, Ca-Ci3 aryium, C1-C7; 5 heteroaryl or amino substituted with one or two R1-®-1”; R1-8-1 is independently C1-C7 alkyl or C3-C14 cycloalkyl; R1-9 is independently hydrogen or C1-C7 alkyl; R2 is C2-C7 alkyl, C3-C14 cycloalkyl or C3-C14 heterocycloalkyl optionally substituted with one, two or three R22; 10 R2'2 is independently halogen or hydroxyl; in any of the above cases, the heteroatoms in the C3-Ci4 heterocycloalkyl, C1-C7 heteroaryls are independently selected from one or more of boron, silicon, oxygen, sulfur, selenium, nitrogen and phosphorus; the number of heteroatoms is independently 1,2,3 or 4; 15 scheme (8): A is C3-C20 cycloalkyl substituted with one or two R!; 137 Xes CHoN;R1 is independently cyano, halogen, -NRV3R1·4, -C(=O) R15, -C(=NR1··6) R17, =NO-R1'9, C1-C7 heteroaryl or C3-C14 heterocycloalkyl optionally substituted with a R1'8; R1·3 and R1'4 are independently hydrogen, -S(=O)2R1·3·1, -C(=O) R1'3'2, -C(=NR: 3 8) 5 NR^^R1'3'6, or C1-C7 alkyl; Ri-3-i and Ri-3-2 are independently C1-C7 alkyl, or C3-C14 cycloalkyl; R1'3'3 is hydrogen; pi-3-s and Ri-3-e are hydrogen; R1·5 is independently -NR1·5-^152, -O153 or C3-C14 heterocycloalkyl; R1-5-1 and R1-5'2 are independently hydrogen, CrC? alkyl or C3-C14 cycloalkyl; R1'5'3 is independently hydrogen or CrC? alkyl; R1'3 is independently oxo; R1'3 is independently hydrogen or C1-C7 alkyl; R2 is C2-C7 alkyl or C3-C14 heterocycloalkyl substituted by an R2'2”; R2'2 is halogen 5 or hydroxyl; scheme (9): A is C3-C2.3 cycloalkyl substituted by an R1; X is CH or N;R1 is -CN, -NR^R1-4, -C(=O) R1'5, = NO-R1'9 or ”C3-C14 ® heterocycloalkyl optionally substituted with an R18; R73 and RV4 are independently hydrogen, -S(=O)2R1·3'1, -C(=O) R1·3'2, -C(=NR1·3' or c1.c7 alkyl; Ri-3-i and 3-2 are independently C1-C7 alkyl, or C3-C14 cycloalkyl; R1'3'3 is hydrogen; !5 Ri-3-s and pi-3-6 are hydrogen; R18 is -NR78 'R: 8 2. -O15'3 or C3-C14 heterocycloalkyl; R1-5-1 and Ri-5-2 are independently hydrogen, C1-C7 alkyl or C3-C14 cycloalkyl; R1'5'3 is independently hydrogen or C1-C7 alkyl; R1'8 is independently oxo; 10 R1'9 is independently hydrogen or C1-C7 alkyl; R2 is C2-C7 alkyl or C3-C14 alkyl heteroacid substituted by an R2'2”; R2'2 is hydroxyl; scheme (10): A is C3-C20 cycloalkyl substituted by an R1; X is CHoN; 15 R1 is -CN, -NR1'3R1-4, -C(=O)R73, ^NO-R1'3, or C3-C14 cycloalkyl heteroacid” optionally substituted with an RV8;IVIA / 10400 138 R1'3 and R1'4 are independently hydrogen, -S^O^R'·3'1, -C(=O)R13·2, -C(=NR1·3· 3)NRl-3-5R1-3-6 or C).C7 alkyl; R1'3-' and ri-3-2 are independently C1-C7 alkyl, or C3-C14 cycloalkyl; R1·3'3 is hydrogen; R1'3'5 and R1-3'9 are hydrogen; R1'5 is -NR1'5·^1·5'2, -O1'5'3 or C3-C14 heterocycloalkyl; ^1-5-1 and Ri-5-2 are independently hydrogen, C1-C7 alkyl or C3-C14 cycloalkyl; R1'5'3 is hydrogen; R1S is independently oxo; R1'9 is independently hydrogen or C1-C7 alkyl; R2 is C2-C7 alkyl or C3-C14 heterocycloalkyl substituted by an R2'2”; R2'2 is hydroxyl; scheme (11): i JWV ¡ A is R1 or ; X is CH or N; R1 is -CN, -NR1^-4, -C(=O)R1'5, = NOR-9, or C3-C14 heterocycloalkyl optionally substituted with an R18; R1-3 and R1-4 are independently hydrogen, -S^O^R1'3'1, -C(=O) R3^2, -C^NR1·3'3) NRVs-SRi-ae, or crc7 alkyl; Ri-3-1 and R1-3-2 are independently C1-C7 alkyl, or C3-C14 cycloalkyl; R1'3'3 is hydrogen; R1'35 and raj-s are hydrogen;R15 is -MR1-5·1^-5'2, -O15-3 or C3-C14 heterocycloalkyl; and RV5'2 are independently hydrogen, C1-C7 alkyl or C3-C14 cycloalkyl; R1·5'3 is hydrogen or C1-C7 alkyl; R1'3 is independently oxo; R1'9 is independently hydrogen or C1-C7 alkyl; R2 is C2-C7 alkyl or C3-Cp. heterocycloalkyl substituted by an R2 2”; R2’2 is hydroxyl; scheme (12): A is X is CH or N; 139 R1 is independently -CN, -NR1’3R1’4, -CAOIR17 =NO-R19, or C3-C14 heterocycloalkyl optionally substituted with an R1’8; R1’3 and R1’4 are independently hydrogen, -S(=O)2R1’3·1, -C(=O)R1·3’2, -C(=NR1’3’ ^NR / ’^R1·3·5, or C1-C7 alkyl; Ri-3-1 and Ri-3-2 are independently C1-C7 alkyl, or C3-C14 cycloalkyl; R1’3’3 is hydrogen; ^1-3-5 and Ri-ss are hydrogen; R1’5 is independent -NR1'5·^1·5-2, -O1'5'3, or C3-C14 heterocycloalkyl; R1·5'1 and Ri-5-2 are independently hydrogen, C1-C7 alkyl, or C3-Cu cycloalkyl; R1'5·3 is independently hydrogen or CrCr alkyl;R1'8 is independently oxo; R13 is independently hydrogen or C1-C7 alkyl; IVIA / t / ZUZZ / U I0400 R2 is । , OH or F .; 12. The pyrazolopyrimidine compound represented by formula II according to claim 1 or 2, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof, or the prodrug thereof, characterized in that the pyrazolopyrimidine compound represented by formula II is any of the compounds described in any of the following schemes: scheme A: O 140 0400 141 scheme B: o^ >su1HRMN(400MHz, MeOD)esS8.85(s, 1 H),8.00(t,J = 7.9Hz, 1 H), 7.80 (d, J - 8.1 Hz, 1 H), 7.68 (d, J - 7.7 Hz, 1 H), 7.62 (d, J - 8.6 Hz, 2 H), 7.28 (d, J - 8.6 Hz, 2 H), 5.78 - 5.68 (m, 1 H), 5.06 (d, J = 10.3 Hz, 1 H), 4.95 (s, 1 H), 4.82 (s, 2 H), 3.82 - 3.76 (m, 1 H), 2.81 (s, 1 H), 2.71 (s, 3 H), 2.49 (s, 1 H), 2.08 (d, J = 10.9 Hz, 3 H), 1.94 (d, J = 15.0 Hz, 3 H), 1.72 (s, 4 H), 1.59 (d, J - 7.0 Hz, 6 H); O or YX M, its 1H NMR (400 MHz, CDCh) is δ 8.87 (d, J = 2.1 Hz, 1 H), 7.91 (id, J = 7.9, 1,5 Hz, 1 H), 7.78 (d, J = 8.0 Hz, 1 H), 7,54 (t, J = 7.9 Hz, 2 H), 7,39 (d, J = 7.7 Hz, 1 H), 7,21 (d, J= 8,5 Hz, 2 H), 5.72 (ddt, J=16.4, 10.2,6,2 Hz, 1 H), 5.07 (dd, J=10.2, 1,1 Hz, 1 H), 4.96 (dd, J = 17,1, 1,2 Hz, 1 H), 4.77 (d, J = 6,2 Hz, 2H), 4,25 - 4,10 (m, 2H), 3.95 (s, 1H),2.73 (s, 1H), 2,56 (dt, J = 15.5, 10.8 Hz, 1 H), 2,28 (d, J = 7.9 Hz, 1 H), 2,14 (d, J = 10.6 Hz, 1 H), 2.05 - 1.97 (m, 1 H), 1.78 (dd, 7= 19.0, 8,5 Hz, 1 H), 1.67 (dt, J = 10,1,6,1 Hz, 3 H), 1.61 (s, 6 H), 1,59 - 1,44 (m, 1 H), 1,34 - 1,26 (m, 3 H); o Jl J ,N hn''^n'~n ο Y oSh , SU 1H NMR (400 MHz, MeOD) es δ 8.84 (d, J= 1,4 Hz, 1 H), 8.00 (td, J = 7.9, 4.0 Hz, 1 H), 7.83 - 7.76 (m, 1 H), 7.67 (dd, J = 7.7, 0.7 Hz, 1 H), 7.60 (dd, J = 8.4, 5.7 Hz, 2H), 7,19 (dd, J= 13.2, 8.6 Hz, 2H), 5.73 (ddd, 17.0, 6,1,4,1 Hz, 1 H), 5.08 -5.03 (m, 1 H), 4.95 (día, J = 1,3 Hz, 1 H), 4.86 - 4.79 (m, 2 H), 2.72 (s, 1 H), 2,58 (s, 1 H), 2,27 (d, J = 6.7 Hz, 142 1 Η), 2,13 (d, J = 10.0 Hz, 1 H), 1.96 (d, J= 10,2 Hz, 1 H), 1.80 - 1.66 (m, 4H), 1.64- 1,52 (m, 7H); O I ' , su 1H RMN (400 MHz, CDCI3) es δ 8.86 (d, J = 4,2 Hz, 1 H), 7.97 - 7.88 (m, 1 H), 7.79 (d,J= 8.0 Hz, 1 H), 7,53 (dd, J = 12.3, 8,5 Hz, 2H), 7.39 (d, J=7.6 Hz, 1 H), 7,28 - 7,15 (m, 2 H), 5.80- 5.65 (m, 1 H), 5.06 (d, J = 10.0 Hz, 1 H), 4.95 (d, J= 17,1 Hz, 1 H), 4.77 (d, J = 6.0 Hz, 2H), 3,10 (d, J = 12,1 Hz, 3 H), 2.98 (s, 3 H), 2.67 - 2,57 (m, 1 H), 2,14 (dd, J = 20.9, 10,3 Hz, 1 H), 2.06 - 1.97 (m, 2 H), 1.92 (d, J = 14.0 Hz, 1 H), 1.78 - 1.66 (m, 4 H), 1.61 (s, 6H), 1,49 (dd, J = 22.8, 12,2 Hz, 1 H); λ O V OH Φ , su 1H RMN (400 MHz, CDCI3) es δ 8.85 (d, J - 4.7 Hz, 1 H), 7.91 (dt, J 20 10.7, 7.9 Hz, 1 H), 7.78 (d, J = 7.8 Hz, 1 H), 7,53 (dd, J = 12.0, 8,5 Hz, 2H), 7,39 (dd, J = 7.6, 2,4 Hz, 1 H), 7,22 (dd, J = 19.5, 8,5 Hz, 2H), 5.71 (ddt, J = 16.4, 10.2, 6,2 Hz, 1 H), 5.06 (d, J = 10,2 Hz, 1 H), 4.95 (d, J = 17,1 Hz, 1 H), 4.77 (d, J = 6,1 Hz, 2 H), 4,21 (dd, J = 16.4, 8.6 Hz, 2H), 4,10 - 4.02 (m, 2H), 2.63 - 2,52 (m, 2H), 2,35 - 2,20 (m, 2H), 2,15 - 2.07 (m, 1H), 2.00 (dd, J = 13.4, 3.0 Hz, 2 H), 1.92 - 1.83 (m, 1 H), 1.79 - 1.63 (m, 4 H), 1.60 (s, 6 H), 1,48 (ddd, J = 24.7, 12.5,2,5 Hz, 1 H); , su 1H RMN (400 MHz, CDCb) es δ 8.86 (s, 1 H), 7.93 - 7.85 (m, 1 H), 7.78 (d, 7.8 Hz, 1 H), 7,52 (d, J = 8,5 Hz, 2 H), 7,39 (dd. 7.6, 0.7 Hz, 1 H), 7,19 (d, 8,5 Hz, 2 H), 5.71 (ddt, = 16.4, 10.2, 6,2 Hz, 1 H), 5.05 (dd, J= 10.2, 1,1 Hz, 1 H), 4.94 (dd, J = 17,1, 1,3 Hz, 1 H), 4.77 (d, J = 6,2 Hz, 2H), 4,11 (d, J=8.9Hz, 1 H), 3,24 (t,J=7.0 Hz, 4 H), 2,52-2,43 (m, 1 H), 2,14-2.00 (m, 3 H), 1.92 (d, 11,2 Hz, 4 H), 1.60 (s, 6 H), 1,45 (dt, J = 14.9, 7,5 Hz, 2 H), 1,23- 1.08 (m, 2 H); 143 , su 1H RMN (400 MHz, CDCb) es δ 8.84 (d, J = 3.7 Hz, 1 H), 7.94 (dd, J = 14.8, 6.9 Hz, 1 H), 7.76 (d, J = 7.9 Hz, 1 H), 7,58 - 7,50 (m, 2 H), 7,42 ( dd, J = 7.5, 4,1 Hz, 1H), 7,22 (dd, J = 15.8, 8,5 Hz, 2H), 5.71 (dd, J = 11.5, 5,4 Hz, 2H), 5.07 (d, J = 10,2 Hz, 1H ), 4.95 (d, J = 17,1 Hz, 1 H), 4.77 (d, J = 6,1 Hz, 2 H), 2.82 - 2.72 (m, 1 H), 2.60 (s, 1 H), 2,12 2.01 (m, 3H) , 1.92 (d, J = 12,5 Hz, 1 H), 1.81 - 1.67 (m, 3 H), 1.62 (s, 6 H), 1,54 - 1,43 (m, 1 H), 0.93 - 0.78 (m, 3 H), 0,52 (s , 2H); , su 1H RMN (400 MHz, CDCh) es δ 8.88 (s, 1 H), 7.91 (t, J = 7.9 Hz, 1 H), 7.77 (d, J = 7.9 Hz, 1 H), 7,56 (d, J = 8,5 Hz, 2 H), 7,40 (d, J = 7,4 Hz, 1 H), 7,19 (d, J = 8,5 Hz, 2 H), 5.78-5.66 (m, 1 H), 5.07 (dd, J = 10.2, 1.0 Hz, 1 H), 4.96 (dd, J = 17,1 , 1,2 Hz, 1 H),4.77 (d, J = 6,2 Hz, 2 H), 4,42 (d, J = 7.6 Hz, 1 H), 3,49 - 3,35 (m, 1 H), 3.04 (s, 3 H), 2,57 - 2,46 (m, 1H), 2,29-2,17 (m, 2H), 2.05- 1.96 (m, 8H), 1,56-1.65 (m, 2H), 1,41-1,50 (m, 2H); o '-2C , su 1H RMN (400 MHz, MeOD) es δ 8.84 (s, 1 H), 8.02 (m, 1 H), 7.80 (m, 1 H), 7.72-7,58 (m, 3 H), 7,25 (m, 2 H), 5.73 (ddt, J = 16.5, 10.3, 6,1 Hz, 1 H), 5.05 (dd, J = 10.2, 1.0 Hz, 1 H), 4.95 (d, 1 H), 4.83 (d, J = 6,1 Hz, 2 H), 3,54-3,42 ( m, 1 H), 2,59 (m, 1 H), 2,14 (m, 1 H), 1.98 (m, 2 H), 1.83 (m, 1 H), 1.68 (m, 2 H), 1.60 (s, 6 H), 1,50 (m , 2H); , su Ή RMN (400 MHz, DMSO) es δ 10,28 (s, 1 H), 8.88 (d, J = 1.8 Hz, 1 H), 8.09 - 7.97 (m, 1 H), 7.75 (d, J = 8,4 Hz, 1 H), 7.66 (dd, J = 20.6, 8,5 Hz, 3 H), 7,19 (dd, J = 144 11,1,8.7 Hz, 2 Η), 5.74 - 5.61 (m, 1 Η), 5.00 (d, J = 10,2 Hz, 1 H), 4.82 (re, J = 17,1 Hz, 1 H), 4.69 (re, J = 5,5 Hz, 2 H), 3,23 (s, 1 H), 2.74 (t, J = 12,1 Hz, 1 H), 2,53 (s, 1 H), 2,12 (re, J = 10,1 Hz, 1 H), 1.98 (re, J = 13,2 Hz, 1 H), 1.82 (re, J = 13,2 Hz, 2 H), 1.77-1,57 (m, 3 H), 1,49 (re, J = 18,2 Hz, 6H); 5 o i! , su ’H RMN (400 MHz, DMSO) es δ 10,27 (s, 1 H). 8.89 (s, 1 H), 8,12 (s, 1 H), 7.74 (dd, J = 22.6, 8,3 Hz, 3 H), 7.64 (d, J = 7,3 Hz, 1H), 7,37 (d, J = 8,5 Hz, 2H), 5.76-5.61 (m, 1H), 5,34 (s, 1H), 5.01 (dd, J = 10.3, 1,2Hz, 1H), 4.84 (d, J = 17,1 Hz, 1 H), 4.70 (d, J = 5.7 Hz, 2 H), 3.62 (s, 1 H), 3,12 (s, 1 H), 2.71-2,58 (m, 8 H), 2,38 (d, J = 9,2 Hz, 2 H), 1,47 (s, 6H), 1,32-1,24 (m, 1 H); , su ’H RMN (400 MHz, DMSO) es δ 10,26 (s, 1 H), 8.88 (s, 1 H), 8.07 (t, J = 7.8 Hz, 1 H), 7.76 (d, J = 8.0 Hz, 1 H), 7.65 (dd, J = 14.5, 7.9 Hz, 2 H), 7,22 (d, J = 8,5 Hz, 2 H), 5.74 - 5.60 (m, 1 H), 5,35 (s, 1 H), 5.00 (d, J = 10,3 Hz, 1 H ), 4.83 (d, J = 17,1 Hz, 1 H), 4.69 (d, J = 5.6 Hz, 2 H), 3.74 (s, 3 H), 3,24 - 3,15 (m, 1 H), 2.77 (t, J = 12.0 Hz , 1 H), 2,37 (d, J = 14.0 Hz, 1 H), 2,25 (td, J = 13.4,4.6 Hz, 1 H), 1.99- 1.84 (m, 3 H), 1.67- 1,50 (m, 2 H), 1,49 (d, J= 14.0 Hz, 6 H); ΐ í-33 , su ’H NMR (400 MHz, MeOD) es δ 8.86 (s, 0 H), 8,11-8.01 (m, 1 H), 7.94 (d, J = 7.9 Hz, 2 H), 7.67 (d, J = 7.6 Hz, 2 H), 7.62 (d, J = 8.6 Hz, 2H), 7,28 (d, J = 8,5 Hz, 2H), 5.83-5.74 (m, 1H), 5.09 (dd, J = 7.9, 4,4 Hz, 3H), 4.98 (dd, J = 17,1, 1,3 Hz, 2H ), 4.85 (d, 35 J = 6.7 Hz, 2 H), 2.87 (s, 1 H), 2.64 (s, 1 H), 2,47 (s, 3 Η), 1.97 - 1.67 (m, 8 H); 145 , su 1H NMR (400 MHz, MeOD) es δ 8.87 (d, J = 6.6 Hz, 1 H), 8.06 (t, J = 7.9 Hz, 1 H), 7.95 (d, J = 7.9 Hz, 1 H), 7.68 (dd, J = 7.8, 5,4 Hz, 2 H) , 7.61 (d, J = 8.6 Hz, 1 H), 7,41 (d, J - 8,4 Hz, 1 H), 7,24 (t, J = 8.7 Hz, 1 H), 5.84 - 5.72 (m, 1 H), 5.09 (d, J = 6,2 Hz, 2 H), 5.07 (d, J - 1,3 Hz, 1 H), 5.02-4.94 (m, 2 H), 4.90 (s, 2 H), 4.84 (d, J - 6.7 Hz, 2 H), 3,15 (d, J = 2.6 Hz, 1 H), 3.08 (s, 1 H), 2.95 (s, 1 H), 2.71 (s, 1 H), 2,43 (s, 1 H), 1.93-2.03 (m, 3 H), 1.76 (s , 2 H), 1,51 (s, 1 H), 1,31 (d, J = 4,3 Hz, 3 H), 0.89 (dd, J = 20,1,9.0 Hz, 4 H); o , su Ή RMN (400 MHz, CDCI3) es δ 8.87-8.79 (m, 1H), 8,14-8.07 (m, 1H), 8.04-7.96 (m, 1H), 7.89-7.80 (m, 1H), 7.61-7,50 (m, 2H), 7,38-7,32 ( m, 1H), 7,25 - 7,19 (m, 1H), 7.01 (t, J = 3,4 Hz, 1H), 5.72 (ddd, J = 16.6, 11,1,8.6 Hz, 1H), 5,17-5.09 (m, 2H) , 5.04 4.98 (m, 1H), 4.98 - 4.92 (m, 1H), 4.87 - 4.77 (m, 2H), 4.73 - 4.64 (m, 2H), 4,20 - 4.06 (m, 1H), 3,47 - 3,38 ( m, 1H), 3,38 - 3,29 (m, 1H), 3.05-2.98 (m, 1H), 2,49-2,35 (m, 2H), 2,27-2,17 (m, 1H), 2.07-1.86 (m, 4H), 1.75-1.60 (m, 3H); O UN -O OH 1-37 sO , SU Ή RMN (400 MHz, CDCh) es δ 8.77 (s, 1H), 8,16-8.07 (m, 1H), 8.03 (d, J = 7.6 Hz, 1H), 7.83-7.75 (m, 1H), 7,56 (dd, J = 12.6,6,1 Hz, 2H ), 7,33 (d, J = 8,5 Hz, 1H), 7,21 (d, J = 8,5 Hz, 1H), 5.72 (dd, J = 17.0, 10,3 Hz, 1H), 5,13 (dd, J = 9,1,6,1 Hz , 2H), 4.96 (d, J = 17.0 Hz, 2H), 4.81 (d, J = 7,2 Hz, 2H), 4.69 (d, J = 6,2 Hz, 2H), 4,41 - 4,28 (m, 2H), 3.86 (s, 1 H), 3.77 (t, J = 6.6 Hz, 1 H), 3.63-3,50 (m, 2 H), 2.98 (m, 1 H),2,15(m, 1 H), 1.97 (dd, J = 18.9, 9.6 Hz, 2H), 1.78 (d, J = 5.0 Hz, 2H), 1.65 (d, J = 8.7 Hz, 2H); 146 Ν , su 1Η RMN (400 MHz, CDCh) es δ 8.69 (s, 1 Η), 8,18 (d, J = 8.0 Hz, 1 Η), 8,10 (dd, J = 17.9, 7.6 Hz, 1 H), 7.81- 7.72 (m, 1 H), 7.63-7,49 (m, 2 H)), 7,25 (d, J = 8,4 Hz, 1 H), 7,19 (d, J = 8,3 Hz, 1 H), 5.70 (d, J = 6.8 Hz, 1 H), 5,15 (d, J = 10,1 Hz, 1 H), 5,14 - 5.07 (m, 1H), 4.95 (d, J = 16.6 Hz, 1H), 4.83 (t, J = 6.7 Hz, 2H), 4.71 (s, 2H), 2,54 (dd, J = 24.9, 12.6 Hz , 2H), 2,30 (d, J = 11,2 Hz, 1H), 2,18 (d, J = 13,5 Hz, 1H), 2.02 (d, J = 12.9 Hz, 1H), 1.961.80 (m, 2H), 1.78 (d, J= 16,1 Hz, 1 H), 1,49 (dd, J = 26.4, 11,2 Hz, 2 H); , su Ή RMN (400 MHz, metano!-D4) es δ 8.85 (d, J= 1,1 Hz, 1 H), 8.05 (id, J = 7.9, 4.8 Hz, 1 H), 7.96 - 7.86 (m, 1 H), 7.67 (d, J = 7.6 Hz, 1 H), 7,59 (ddd, J = 9.2, 4.6, 2,3 Hz, 2H), 7,25 - 7,19 (m, 1H), 7,19 - 7,11 (m, 1H), 5.78 (ddt, J = 16.5, 10,1,6,1 Hz, 1 H),5,12 - 5.07 (m, 2 H), 5.06 (t, J = 1,3 Hz, 1 H), 4.98 (dd, J = 17.0, 1,4 Hz, 1 H), 4.90 (d, J = 1,4 Hz, 2 H), 4,25-4,19 (m, 1 H), 4,14 (dd, J = 14,1,7,1 Hz, 1 H), 2,34 - 2,12 (m, 2H), 2.07 (dd, J= 17.0, 4,1 Hz, 1H), 1.99- 1.82 (m, 1H), 1.74- 1.65 (m, 2H), 1.65- 1,53 (m, 2H), 1,31 (d, J = 4,2 Hz, 3 H), 1,29- 1,25 (m,2H); cooh , su 3H RMN (400 MHz, metanol-d4) es δ 8.84 (s, 1 H), 8.05 (t, J = 7.9 Hz, 1 H), 7.92 (d, J = 8,1 Hz, 1 H), 7.66 (dd, J = 7.6, 0.9 Hz, 1 H). 7.63 - 7,53 (m, 2H), 7,22 7,14 (m, 2H), 5.84 - 5.74 (m, 1H), 5,10 - 5.07 (m, 2H), 5.06 (q, J = 1,3 Hz, 1H), 4.98 (dq, J = 17.0, 1,4 Hz. 1 H), 4.89 (dt, J = 6,1, 1.4 Hz, 2 H), 2.71 (d, J = 6.9 Hz. 1 H), 2,59 (s, 1 H), 2.24 (dd, J = 16.4 , 7.8 Hz, 2 H), 2.04 (d, J = 8.5 Hz, 1 Η), 1.73 (id, J = 10.9, 6.8 Hz, 6 H); scheme C: 147 ΜΛ / t / ZUZZ / U I0400 scheme D: (1-1-1), its NMR Ή (400 MHz, MeOD) is ¿5 8.85 (s, 1 H), 8.46 (s, 2 H), 7.99 (t, J 7. = 7), 8.0 Hz, 1 H), 7.65 (dd, J = 16.6, 8.1 Hz, 3 H ), 7.22 (d, J = 8.6 Hz, 2 H), 5.73 (ddt, J = 16.3, 10.2, 6.1 Hz, 1 1 H (dd 3 = J), 5.
5. H), 4.93 (dd, J = 17.1, 1.3 Hz, 1 H), 4.82 (d, J = 6.1 Hz, 2 H), 2.90 (s, 6 H), 2.60 (d, J = 8.4 Hz, 1 H), 2,21 (H, J = 10 Hz (d.2), 2,6 1.70 (d, J = 11.4 Hz, 4 H), 1.59 (s, 6 H); on / = il J HN NN ή tu Y OH V (1-1-2), on !H NMR (400 MHz, CDCI3) is δ 8.86 (s, 1H), 8.54 (s, 1H), 7.95 (t, J = 7.9 Hz, 1 H), H 7.7 (8.75) (1 H (d, J = 8.5 Hz, 2H), 7.43 (d, J = 7.6 Hz, 1 H), 7.32 (d, J = 8.5 Hz. 2 H). 5.72 (ddt. J = 16.5, 10.3,6.2 Hz. 1 H), 5.06 (d, J = 10.2 Hz, 1 H), 4.95 (dd, J = 17.1, 1.0 Hz, 1H), 4.75 (d, J3, 02,1(), 2.93 (m, 1H), 2.68 (s, 6H), 2.32 (m, 2H), 1.84 (m, 6H), 1.60 (s, 6H); 149 > π N c N N A X ·Ν~' OH ,N (1-3-1), su ΊΗ RMN (400 MHz, CDC!3) es δ 8.87 (s, 1H), 7.90 (i, J = 7.9 Hz, 1H), 7.78 (d, J = 8.0 Hz, 1H), 7,53 (d, J = 8,5 Hz, 2H), 7,39 (dd, J = 7.6, 0,5 Hz, 1 H), 7,20 (d, J = 8,5 Hz, 2 H), 5.72 (ddt, J = 16.4, 10.2, 6,2 Hz, 1 H), 5.06 (dd, J = 10.2, 1.0 Hz, 1 H), 4.95 (dd, J = 17,1, 1,2 Hz, 1 H), 4.76 (d, J = 6,2 Hz, 2 H), 4.04 (s, 1 H), 2.66 (m, 4 H), 2,58 - 2,47 (m, 1 H) , 2,16 (m, 4 H), 1.96 (m, 2 H), 1.87- 1.78 (m, 4 H), 1.60 (s, 6 H), 1,58- 1,39 (m, 4 H); o j| i N--- / HN^A 'N OH ó A \J (I-3-2), su 1H RMN (400 MHz, CDCi3) es δ 8.87 (s, 1H), 7.92 (t, J = 7.9 Hz, 1H), 7.80 (d, J = 8.0 Hz, 1H), 7,52 (d, J = 8,5 Hz, 2H), 7,38 (d, J = 7.6 Hz, 1 H), 7,29 (t, J = 4,2 Hz, 2H), 5.79-5.66 (m, 1 H), 5.06 (05,3-10.2, 1.0 Hz, 1 H), 4.96 (dd, J = 17,1, 1,2 Hz, 1 H), 4.77 (d, J = 6,2 Hz, 2 H), 4.02 (s, 1 H), 2.70 - 2,50 (m, 5 H), 2,26 (s, 1 H), 1.98 (m, 4 Η), 1.82 (s, 4H), 1.69- 1,56 (m, 10 H); O / = ¡i J nhínA ^ A.An o Y OH N V (1-8-1), su A RMN (400 MHz, CDCI3) es δ 8.86 (s, 1 H), 7.93 - 7.85 (m, 1 H), 7.78 (d, J = 7.8 Hz, 1 H), 7,52 (d, J = 8,5 Hz, 2 H), 7,39 (dd, J = 7.6, 0.7 Hz, 1 H), 7,19 (d, J = 8,5 Hz, 2 H), 5.71 (ddt, J = 16.4, 10.2, 6,2 Hz, 1 H), 5.05 (dd, J = 10.2, 1,1 Hz, 1 H), 4.94 (dd , J = 17,1, 1,3 Hz, 1 H), 4.77 (re, J = 6,2 Hz, 2 H), 4,11 (re, J = 8.9 Hz, 1 H), 3,24 (t, J = 7.0 Hz, 4 H), 2,52-2,43 (m, 1 H), 2,14-2.00 (m, 3H), 1.92 (d, J = 11,2 Hz, 4 H), 1.60 (s, 6 H), 1,45 (dt, J = 14.9, 7,5 Hz, 2 H), 1,23 - 1.08 (m, 2 H); 150 QQfrQ Ln / ZZnZ / 3 / ΥΙΛ (1-8-2), su Ή RMN (400 MHz, CDCh) es 58.87 (s, 1 H), 7.92 (d, J = 7.8 Hz, 1 H), 7.80 (d, J = 8.0 Hz, 1 H), 7,52 (d, J = 8,4 Hz, 2 H), 7,39 (d, J = 7.6 Hz, 1 H), 7,29 - 7,25 (m, 2 H), 5.82-5.63 (m, 1 H), 5,12-4.91 (m, 2 H), 4.78 (d, J = 6,2 Hz, 2 H), 4.01 (s, 1 H), 3,17 (s, 4 H), 2,53 (s, 1 H), 2,33 (s, 1 H), 2.06 (d, J - 4,4 Hz, 2 H), 1.89 (d, J = 11.6 Hz, 2 H), 1.75 (re, J = 14.1 Hz, 2 H), 1.59 (re, J = 17.2 Hz, 8 H), 1.46 (t, J = 13.1 Hz, 2 H); 'Ν·- (1-15-1), su Η NMR (400 MHz, MeOD) δ 8.84 (s, 1 H), 8.04 (t, J = 7.9 Hz, 1 H), 7.92 (d, J = 8.1 Hz, 1 H), 7.67 (d, J = 7.6 Hz, 1 H), 7.60 (d, J = 8.6 Hz, 2 H), 7.21 (d, J = 8.6 Hz, 2 H). 5.78 (ddt, J = 16.3, 10.3, 6.1 Hz, 1 H), 5.12 - 5.05 (m, 3 H), 4.98 (dd, J = 17.1, 1.3 Hz, 1 H), 4.89 (d, J = 6.1 Hz, 2 H), 4.84 (s, 2 H), 3.68 (s, 2 H), 2.97 - 2.86 (m, 1 H), 2.66 (s, 6 H), 2.60-2.50 (m, 1 H), 2.15 (d, J=8.6 Hz, 2 H), 2.04 (d, J= 9.0 Hz, 2 H), 1.66- 1.54 (m, 4 H); x'h (1-15-2), su Ή NMR (400 MHz, MeOD) δ 8.83 (s, 1 H), 8.04 (t, J = 7.9 Hz, 1 H), 7.92 (d, J = 8.0 Hz, 1 H), 7.67 - 7.62 (m, 1 H), 7.59 (d, J = 8.6 Hz, 2 H), 7.29 (d, J = 8.5 Hz, 2 H), 5.76 (ddt, J = 16.3, 10.2, 6.1 Hz, 1 H), 5.10-5.02 (m, 3 H), 4.96 (dd, J = 17.1, 1.3 Hz, 1 H), 4.87 (d, J = 6.8 Hz, 2 H), 4.82 (d, J = 6.8 Hz, 2 H), 2.73 (d, J = 4.2 Hz, 1 H), 2.29 (d, J = 21.9 Hz, 7H), 2.04- 1.90 (m, 4 H), 1.66 (dd, J = 15.6, 6,1 Hz, 4 H); 151 (1-36-1), su 1H RMN (400 MHz, CDCh) es δ 8.88 (d, J = 2.6 Hz, 1 H), 8.09 (dd, J = 15.0, 7.8 Hz, 1 H), 7.99-7.83 (m, 2 H), 7,54 (t, J = 9,5 Hz, 2 H), 7,39 (d, J = 8.7 Hz, 1 H), 7,21 (d, J = 8,5 Hz, 1 H), 5.74 (dq, J = 10.5, 5.9 Hz, 1 H), 5,12 (1, J = 8.8 Hz, 3 H), 4.99 (d, J = 17,1 Hz, 1 H), 4.80 (d, J = 6,3 Hz, 2 H), 4.67 (d, J = 6.0 Hz, 2 H), 3,39-3,24 (m, 4 H), 2.602,34 (m, 3 H ), 2,14 (dt, J = 14.0, 6.8 Hz, 3 H), 1.96 (d, J = 10.8 Hz, 4 H), 1,55-1,37 (m, 2 H), 1,27-1,12 (m, 2 H); (I-36-2), su Ή NMR (400 MHz, MeOD) es 6 8.86 (s, 1 H), 8.02 (dt, J = 24.0, 7.9 Hz, 3 H), 7.64 (dd, J = 27,1, 8,1 Hz, 3 H), 7,27 (t, J = 8.6 Hz, 2 H), 7.01- 6.91 (m, 3 H), 6.72-6.64 (m, 3 H), 5.79 (ddd, J = 16.3, 11.2, 6,1 Hz, 1 H), 5,10-5.05 (m, 2 H), 4.85 (d, J = 6.8 Hz, 2H), 2,57 (d, J = 10.7 Hz, 1H), 2,48-2,28 (m, 3H), 2,23-2.06 (m, 3H), 1.98-1.71 (m, 6H), 1,58 (dd, J-23.2, 12.9 Hz, 3 H), 1,44 (ddd. J= 16,1, 13.2, 3,5 Hz, 2 H), 1,19-1.00 (m,2H); (1-41-1), su 1H NMR (400 MHz, cioroformo-d) es δ 9.00 (s, 1 H), 8,30 (d,J = 8.6 Hz, 1 H), 8,22 (d, J = 2,4 Hz, 1 H), 7.96 (t, J = 7.9 Hz, 1 H), 7.73 (dd, J = 8,1, 0.8 Hz, 1 H), 7,55 (dd, J = 8.7, 2,4 Hz, 1 H), 7.44 (dd, J = 7.7, 0.8 Hz, 1 H), 5.77 - 5.66 (m, 1 H), 5,12 5.05 (m , 1H), 4.97 (dq, J = 17.0, 1,4 Hz, 1H), 4.76 (dt, J = 6.3, 1,3 Hz, 2H), 2.70 (s, 1H), 2,56 (s. 6H), 2,23 (q, J = 9,5 Hz, 4 H), 2,11 -2.01 (m, 4 H), 1,58 (t, J = 10,3 Hz, 6 H); 152 QQfrQ I η / 77Π7 / =1 / ΥΙΛ (1-41-2), su ’Η RMN (400 MHz, cloroformo-d) es Ó8.99 (s, 1 H), 8,54 (s, 1 H), 8,32 (d, J = 8.7 Hz, 1 H), 8,26 (d, J = 2,4 Hz, 1 H) , 8,10 (t, J = 7.7 Hz, 1 H), 7.92 (s, 1 H), 7.78 (dd, J = 8,1,0.8 Hz, 1 H), 7,47-7,41 (m, 1 H), 5.79-5.71 (m, 1 H) ),5.08 (dq, J = 10,1, 1,2 Hz, 1 H), 4.97 (dq, J = 17.0, 1,3 Hz, 1 H), 4.77 (dt, J = 6.2, 1,4 Hz, 2 H), 3.99 (s, 1 H) , 2.75 (d, J = 11.0 Hz, 1 H), 2,52 (s, 6 H), 2,32 - 2,18 (m, 1 H), 2.09 (d, J = 14,4 Hz, 4 H), 1,31 (d, J = 22.8 Hz, 4H); where, / means that the cis-trans conformation is uncertain; scheme E: oi¡ ή V (1-8-1), its Ή NMR (400 MHz, CDCIs) has a peak of 1.23-1.08; where, / means that the cis-trans conformation is uncertain; scheme F: (1-1-1) with a retention time of 10.55 min under the following conditions: Agilent 1260 high-performance liquid chromatograph; mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; column time: 15 mins; column type: Waters' Xselect, 5 pm, 4.6 × 250 mm; gradient elution, 5% mobile phase B -> 50% mobile phase B; 153 (1-1-2) with a retention time of 10.78 min under the following conditions: Agilent 1260 high performance liquid chromatograph; mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; column time: 15 minutes; column type: Waters'Xselect, 5 pm, 4.6 x 250 mm; gradient elution, 5% mobile phase B --> 50% mobile phase B; VJ (1-3-1) with a retention time of 11.01 min under the following conditions: Agilent 1260 high-performance liquid chromatograph; mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; column time: 15 minutes; column type: Waters'Xselect, 5 pm, 4.6 x 250 mm; gradient elution, 5% mobile phase B -> 50% mobile phase B; (I-3-2) with a retention time of 11.20 min under the following conditions: Agilent 1260 high-performance liquid chromatograph; mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; column time: 15 minutes; column type: Waters'Xselect, 5 pm, 4.6 x 250 mm; gradient elution, 5% mobile phase B -> 50% mobile phase B; 154 η IVIA / I0400 xZ (1-8-1) with a retention time of 10.78 min under the following conditions: Agilent 1260 high-performance liquid chromatograph; mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; column time: 15 minutes; column type: Waters' Xselect, 5 μm, 4.6 x 250 mm; gradient elution, 5% mobile phase B -> 50% mobile phase B; or V (1-8-2) with a retention time of 11.00 min under the following conditions: Agilent 1260 high-performance liquid chromatograph; mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; column time: 15 minutes; column type: Waters' Xselect, 5 μm, 4.6 x 250 mm; gradient elution, 5% mobile phase B -> 50% mobile phase B; or χNχ (1-15-1) with a retention time of 7.02 min under the following conditions: Agilent 1260 high performance liquid chromatograph; mobile phase A: water 30 (0.1% formic acid), mobile phase B: acetonitrile; column time: 15 minutes; column type: Waters'Xselect, 5 μm, 4.6 x 250 mm; gradient elution, 5% mobile phase B -> 95% mobile phase B; 155 HN' Ή' r-0 OH conditions: (1-15-2) with a retention time of 7.16 min under the following conditions: Agilent 1260 high-performance liquid chromatograph; mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; column time: 15 minutes; column type: Waters'Xselect, 5 pm, 4.6 x 250 mm; gradient elution. 5% mobile phase B -> 95% mobile phase B; or V (1-36-1) with a retention time of 7.14 min under the following conditions: Agilent 1260 high-performance liquid chromatograph; Mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; column time: 15 minutes; column type: Waters'Xselect, 5 pm, 4.6 x 250 mm; gradient elution, 5% mobile phase B -> 95% mobile phase B; ov (I-36-2) with a retention time of 7.15 min under the following conditions: Agilent 1260 high-performance liquid chromatograph; mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; column time: 15 minutes; column type: Waters' Xselect, 5 pm, 4.6 x 250 mm; gradient elution, 5% mobile phase B -> 95% mobile phase B; or HN' OH (1-41-1) with a retention time of 6.17 min under the following 156 conditions: Agilent 1260 high-performance liquid chromatograph; mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; Column time: 15 minutes; column type: Waters'Xselect, 5 pm, 4.6 x 250 mm; gradient elution, 5% mobile phase B --> 95% mobile phase B; ΊL / t / ZUZZ / UI 0400 (1-41-2) with a retention time of 6.28 min under the following conditions: Agilent 1260 high-performance liquid chromatograph; mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; column time: 15 minutes; column type: Waters'Xselect, 5 pm, 4.6 x 250 mm; gradient elution, 5% mobile phase B --> 95% mobile phase B; where, / means that the cis-trans conformation is uncertain; scheme G: ii 157.
13. A method for preparing the pyrazolopyrimidine compound represented by formula II according to at least one of claims 1 to 12, the method being characterized in that it is any of the following methods: method 1, comprising the following steps: step I, oxidizing compound II-1A by an oxidant in an organic solvent to obtain compound B; step II, reacting compound II-1B with compound II-1C in an organic solvent and under alkaline conditions to obtain compound II; MA / t / ZUZZ / UI0400 method 2, comprising the following steps: step I, hydrolyzing compound II-2A (R' is -(C = O)-OC2H5) to obtain compound II-2B (R' is -(C = O)-OH); In step II, a condensation reaction is carried out between compound II-2B and an amino compound in an organic solvent to obtain compound II (R1 is -(O = Oj-NR1·5·^1·5'2); 14. A compound represented by the formula 11-1C: Á ÍMC characterized in that, X is CH or N, A is as defined in at least one of claims 1-12.
15. The compound represented by formula II-1C according to claim 14, characterized in that the compound is a compound represented by formula II-1C: 158 A 1C QQfrQ Ln / 77n7 / q / YIA where, A is a C3-C20 cycloalkyl substituted by an R1, R1 is -NR14R14 or -C (= O) RV5 and R1' 3, R14 and RM are as defined in at least one of claims 1-12.
16. The compound represented by the formula IMG according to claim 14, characterized in that the compound is any of the compounds described in any of the following schemes: scheme a: scheme b: H,N— / V- / \= / \...... / < its H NMR (400 MHz, CDCh) is δ 7.08 - 6.96 (m. 2H), 6.70 - 6.60 (m, 2H), 3.57 (s, 2H), 3.22 (t, J = 7.0 Hz. 4H), 2.38 (tt, J = 12,1,3,2 Hz, 1H ), 2.15 1.95 (m, 5H), 1.95 - 1.81 (m, 4H), 1.51 - 1.30 (m, 2H), 1.21 - 1.04 (m, 2H); h2n—# y— / Yn^ o, ' λ— / , its 1H NMR (400 MHz, MeOD) is δ 7.10 - 6.97 (m, 2 H), 6.74 - 6.63 (m, 2 H), 4.22 - 4.08 (t, J = 8.0 Hz, 4 H), 3.47 - 3.38 (m, 1H), 2.61 - 2.52 (m, 1H), 2.52 - 2.28 (m, 2H), 1.92 - 1.62 (m, 8H).
17. An application of substance X in the preparation of kinase inhibitors or medicaments; characterized in that the medicament can be used to treat and / or prevent diseases or cancers related to the WEE1 kinase; substance X is the pyrazolopyrimidine compound represented by formula II according to at least one of claims 1 to 12, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof, or the prodrug thereof.
18. A pharmaceutical composition comprising substance X and a pharmaceutical excipient; characterized in that substance X is the pyrazolopyrimidine compound represented by formula II according to at least one of claims 1 to 12, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof, or the prodrug thereof.
19. A combination comprising substance X and a cancer drug, characterized in that substance X is the pyrazolopyrimidine compound represented by formula II according to at least one of claims 1 to 12, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof, or the prodrug thereof.
20. Application of the combination according to claim 19 characterized in that it is for the preparation of a medicament to prevent and / or treat cancer.
21. An application of substance X in the preparation of a medicament, the medicament in combination with an anticancer drug used to prevent and / or treat cancer; characterized in that substance X is the pyrazolopyrimidine compound represented by formula I! according to at least one of claims 1 to 12, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof, or the prodrug thereof.
22. An application of an anticancer drug in the preparation of a medicament, the medicament in combination with substance X used to prevent and / or treat cancer; characterized in that substance X is the pyrazolopyrimidine compound represented by formula II according to at least one of claims 1 to 12, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof, or the prodrug thereof.
23. A pharmaceutical composition characterized in that it comprises the combination according to claim 19 and a pharmaceutical excipient.
24. A drug combination kit characterized in that it comprises pharmaceutical composition A and pharmaceutical composition B; pharmaceutical composition A comprises substance X and pharmaceutical excipients; pharmaceutical composition B comprises anticancer drugs and pharmaceutical excipients; substance X is the pyrazolopyrimidine compound represented by formula II according to at least one of claims 1 to 12, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof, or the prodrug thereof.
25. A method for treating and / or preventing WEE1 kinase-related diseases or cancers, characterized in that it comprises administering a therapeutically effective amount of substance X to a patient; substance X being the pyrazolopyrimidine compound represented by formula II according to at least one of claims 1 to 12, the pharmaceutically acceptable salt thereof, the solvate thereof, the solvate of the pharmaceutically acceptable salt thereof, the metabolite thereof, or the prodrug thereof, 26. A method for treating and / or preventing cancer characterized in that it comprises administering a therapeutically effective amount of the combination according to claim 19 to a patient.