Compounds and their use for treatment of hemoglobinopathies

Abstract

This document discloses compounds and methods for the prevention and / or treatment of heme disorders. It also provides examples of such compounds used in such methods. Furthermore, it discloses pharmaceutical compositions comprising such compounds used in such methods for the prevention or treatment of heme disorders.

Description

Compounds and Their Use in Treating Hemoglobinopathies Compounds and methods for preventing and / or treating hemoglobinopathies are disclosed herein. Compounds for such methods are also provided herein. Pharmaceutical compositions are also disclosed, which comprise such compounds for such methods for preventing or treating hemoglobinopathies. Hemoglobin is an iron-containing metalloprotein present in red blood cells. Hemoglobin transports oxygen to various tissues throughout the body. Fetal hemoglobin (HbF) is present in fetal red blood cells and is involved in the transport of oxygen from the mother to the fetus. After birth, a "fetal switch" occurs, during which erythroid progenitor cells switch from predominantly producing fetal hemoglobin to predominantly producing adult hemoglobin. Adult hemoglobin and fetal hemoglobin are tetramers containing two alpha globin and two beta globin subunits (α2β2) or two alpha globin and two gamma globin subunits (α2γ2), respectively. Fetal hemoglobin binds oxygen more strongly than adult hemoglobin. For example, hemoglobinopathies can occur when adult hemoglobin is expressed abnormally or when the adult hemoglobin protein structure is abnormal. For example, when a person has a point mutation in the beta-globin gene, resulting in the formation of hemoglobin S (HbS), a hemoglobin composed of two normal alpha globin chains and two mutant beta globin chains, sickle cell disease, including sickle cell anemia, occurs. The presence of HbS causes abnormal red blood cell shape, which becomes sickle-shaped when exposed to reduced amounts of oxygen, which impedes blood flow and can lead to hemolysis. Patients with sickle cell disease experience a variety of symptoms, including pain, anemia, bacterial infections, increased risk of stroke, and shortened life expectancy. Another example of a hemoglobinopathy is beta-thalassemia. Beta-thalassemia occurs when the beta chain of hemoglobin is reduced or absent. Without treatment, patients with severe forms of beta-thalassemia can develop many health complications, such as poor growth, skeletal abnormalities, and heart failure. Although beta-thalassemia patients can be treated by blood transfusion, blood transfusion carries the risk of iron overload and leads to complications in the spleen, liver, and heart. Reactivation of functional HbF expression in adult hematopoietic cells has great potential for clinical benefit in patients with hemoglobinopathies such as sickle cell disease and beta-thalassemia. Hydroxyurea is the current standard of care for sickle cell disease, which acts by inducing fetal hemoglobin, but it is limited by different clinical responses, bone marrow toxicity, and carcinogenic risk. Therefore, alternative and more effective treatments for hemoglobinopathies are needed. Compounds of formula (I) are provided herein: (I) and pharmaceutically acceptable salts, tautomers, isotopologues, and stereoisomers thereof, wherein A 1 、A 2 , A 3 , Q and R 3 as defined herein. The present invention also provides compounds of formula (II): (II), and pharmaceutically acceptable salts, tautomers, isotopologues and stereoisomers thereof, wherein Y, Q', R 7 and R 8 as defined herein. The present invention also provides compounds of formula (III): (III), and pharmaceutically acceptable salts, tautomers, isotopologues and stereoisomers thereof, wherein Q'' and R 12 as defined herein. In one aspect, the present invention provides the compounds described in the present invention, such as compounds of formula (I), formula (I'), formula (II), formula (II'), formula (III) or compounds from Table 1. In one aspect, the present invention provides pharmaceutical compositions comprising an effective amount of a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III) described herein or a compound from Table 1 and a pharmaceutically acceptable carrier, excipient or vehicle. In one aspect, the present invention provides a method for treating an individual suffering from a hemoglobinopathy. In another aspect, the present invention provides the use of a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III) or a compound from Table 1 for the treatment or prevention of a hemoglobinopathy, which comprises administering to an individual suffering from a hemoglobinopathy an effective amount of a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III) described herein or a compound from Table 1. In certain embodiments, the methods described herein comprise administering to an individual a therapeutically effective amount of a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III) or a compound from Table 1, or a pharmaceutically acceptable salt, tautomer, isotopologue or stereoisomer thereof. In one aspect, the present disclosure provides the use of a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III) or a compound from Table 1 for treating or preventing a hemoglobinopathy, which comprises administering to an individual suffering from a hemoglobinopathy an effective amount of a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III) or a compound from Table 1 as described herein. In one aspect, the present disclosure provides a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III) or a compound from Table 1 for use as an agent. In a specific embodiment, the present disclosure provides a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III) or a compound from Table 1 for use in a method of treating or preventing a hemoglobinopathy, the method comprising administering to an individual an effective amount of a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III) or a compound from Table 1. In another aspect, the present disclosure provides a method for preparing a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III) or a compound from Table 1 as described herein. The embodiments of the present invention can be more fully understood with reference to the embodiments and examples, which are intended to illustrate non-limiting examples. Cross-reference to Related Applications This application claims the benefit of priority to U.S. Provisional Application No. 63 / 422,847, filed on November 4, 2022, which is incorporated herein by reference in its entirety for any purpose. Definitions As used herein, the terms "comprising" and "including" are used interchangeably. The terms "comprising" and "including" shall be construed as specifying the presence of the stated feature or component mentioned, but not precluding the presence or addition of one or more features or components or groups thereof. Additionally, the terms "comprising" and "including" are intended to include instances covered by the term "consisting of". Thus, the term "consisting of" may be used in place of the terms "comprising" and "including" to provide more specific embodiments of the present invention. The term "consisting of" means that the subject matter has at least 90%, 95%, 97%, 98% or 99% of the stated features or components that make it up. In another embodiment, the term "consisting of" excludes any other features or components from any subsequently recited category, except for features or components that are not essential for the technical effect to be achieved. As used herein, the term "or" shall be construed as an inclusive "or", meaning either or any combination. Thus, "A, B or C" means any of the following: "A; B; C; A and B; A and C; B and C; A, B and C". Exceptions to this definition will occur only when the combination of elements, functions, steps or acts is inherently mutually exclusive in some way. As used herein and unless otherwise specified, "alkyl" is a saturated, partially saturated or unsaturated straight-chain or branched-chain acyclic hydrocarbon having from 1 to 10 carbon atoms, typically from 1 to 8 carbon atoms, or in some embodiments from 1 to 6, from 1 to 4, or from 2 to 6 carbon atoms. Representative alkyl groups include -methyl, -ethyl, -n-propyl, -n-butyl, -n-pentyl and -n-hexyl; and saturated branched-chain alkyl groups include -isopropyl, -sec-butyl, -isobutyl, -tert-butyl, -isopentyl, -neopentyl, tert-pentyl, -2-methylpentyl, -3-methylpentyl, -4-methylpentyl, -2,3-dimethylbutyl and the like. "Alkenyl" is an alkyl group containing one or more carbon-carbon double bonds. "Alkynyl" is an alkyl group containing one or more carbon-carbon triple bonds. Examples of unsaturated alkyl groups include, but are not limited to, vinyl, allyl, -CH=CH(CH 3 )、-CH=C(CH 3 ) 2 、-C(CH 3 )=CH 2 、-C(CH 3 )=CH(CH 3 )、-C(CH 2 CH 3 )=CH 2 、-C≡CH、-C≡C(CH 3 )、-C≡C(CH 2 CH 3 )、-CH 2 C≡CH、-CH 2 C≡C(CH 3 )及-CH 2 C≡C(CH 2 CH 3 )). The alkyl group may be substituted or unsubstituted. When the alkyl group described herein is referred to as "substituted", it may be substituted with any one or more substituents found in the exemplary compounds and examples disclosed herein, as well as halogen; hydroxyl; alkoxy; cycloalkyloxy, aryloxy, heterocyclyloxy, heteroaryloxy, heterocycloalkyloxy, cycloalkylalkyloxy, aralkylalkyloxy, heterocyclylalkyloxy, heteroarylalkyloxy, heterocycloalkylalkyloxy; side oxygen group (=O); amino, alkylamino, cycloalkylamino, arylamino, heterocyclylamino, heteroarylamino, heterocycloalkylamino; imino; imido; formamidine; guanidine; enamine; amide; sulfonylamino; urea, nitrourea; oxime; hydroxylamine; alkoxyamine; aralkylalkoxyamine; hydrazino; hydrazide; hyrazino; azido; nitro; sulfhydryl (-SH), alkylthio; =S; sulfinyl; sulfonyl; aminosulfonyl; phosphonate; phosphinyl; acyl; formyl; carboxyl; ester; carbamate; amide; cyano; isocyanato; isothiocyanato; cyanato; thiocyanato; or -B(OH) 2 . In some embodiments, one or more hydrogens in the alkyl group, such as one, two, three, four, or five hydrogens, may be replaced by halogen. As used herein and unless otherwise specified, "cycloalkyl" is a saturated or partially saturated cyclic alkyl group having 3 to 10 carbon atoms, which may optionally be substituted and has a single cyclic ring or multiple fused or bridged rings. In some embodiments, the cycloalkyl group has 3 to 8 ring members, and in other embodiments, the number of ring carbon atoms ranges from 3 to 5, 3 to 6, or 3 to 7. By way of example, such cycloalkyl groups include monocyclic structures such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 1-methylcyclopropyl, 2-methylcyclopentyl, 2-methylcyclooctyl and the like; or polycyclic or bridged ring structures such as 1-bicyclo[1.1.1]pentyl, bicyclo[2.1.1]hexyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl, adamantyl and the like. Examples of unsaturated cycloalkyl groups particularly include cyclohexenyl, cyclopentenyl, cyclohexadienyl, butadienyl, pentadienyl, hexadienyl. The cycloalkyl group may be substituted or unsubstituted. Such substituted cycloalkyl groups include, for example, cyclohexanol and the like. As used herein and unless otherwise specified, "aryl" is an aromatic carbocyclic group having 6 to 14 carbon atoms, having a single ring (e.g., phenyl) or multiple fused rings (e.g., naphthyl or anthracenyl). In some embodiments, aryl contains 6 to 14 carbon atoms in the ring portion of the group, and in other embodiments contains 6 to 12 or even 6 to 10 carbon atoms. Specific aryl groups include phenyl, biphenyl, naphthyl, and the like. Aryl may be substituted or unsubstituted. The phrase "aryl" also includes groups containing fused rings, such as fused aromatic-aliphatic ring systems (e.g., indanyl, tetrahydronaphthyl, and the like). As used herein and unless otherwise specified, "heteroaryl" is an aromatic ring system having one to four heteroatoms as ring atoms in a heteroaromatic ring system, with the remaining atoms being carbon atoms. In some embodiments, heteroaryl contains 3 to 6 ring atoms in the ring portion of the group, and in other embodiments contains 6 to 9 or even 6 to 10 atoms. Suitable heteroatoms include oxygen, sulfur, and nitrogen. In certain embodiments, the heteroaryl ring system is monocyclic or bicyclic. Non-limiting examples include (but are not limited to) groups such as pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, benzisoxazolyl (e.g., benzo[d]isoxazolyl), thiazolyl, pyrrolyl, pyridyl, pyrimidinyl, pyrazinyl, thienyl, benzothienyl, furyl, benzofuryl, indolyl (e.g., indol-2-one), isoindolin-1-one, azaindolyl, pyrrolopyridyl (e.g., 1H-pyrrolo[2,3-b]pyridyl), indazolyl, benzimidazolyl (e.g., 1H-benzo[d]imidazolyl), azabenzimidazolyl, imidazopyridyl (e.g., 1H-imidazo[4,5-b]pyridyl), pyrazolopyridyl, triazolopyridyl, benzotriazolyl (e.g., 1H-benzo[d][1,2,3]triazolyl), benzoxazolyl (e.g., benzo[d]oxazolyl), benzothiazolyl, benzothiadiazolyl, isoxazolopyridyl, thianaphthyl, purinyl, xanthinyl, adeninyl, guaninyl, quinolinyl, isoquinolinyl, 3,4-dihydroisoquinolin-1(2H)-one, tetrahydroquinolinyl, quinoxalinyl, and quinazolinyl. Heteroaryl may be substituted or unsubstituted. As used herein and unless otherwise specified, "heterocyclic group" is an aromatic ring system (also known as heteroaryl) or a non-aromatic cycloalkyl (also known as heterocycloalkyl) in which one to four ring carbon atoms are independently replaced by heteroatoms. Suitable heteroatoms include oxygen, sulfur, and nitrogen. In some embodiments, the heterocyclic group includes 3 to 10 ring members, while other such groups have 3 to 5, 3 to 6, or 3 to 8 ring members. The heterocyclic group can also be bonded to other groups at any ring atom (i.e., at any carbon atom or heteroatom of the heterocycle). The heterocyclic group can be substituted or unsubstituted. The heterocyclic group encompasses unsaturated, partially saturated, and saturated ring systems, such as imidazolyl, imidazolinyl, and imidazolidinyl (e.g., imidazolidin-4-one or imidazolidine-2,4-dione). The phrase heterocyclic group includes fused ring species, including those heterocyclic groups containing fused aromatic and non-aromatic groups, such as 1-aminotetralin and 2-aminotetralin, benzotriazolyl (e.g., 1H-benzo[d][1,2,3]triazolyl), benzimidazolyl (e.g., 1H-benzo[d]imidazolyl), 2,3-dihydrobenzo[1,4]dioxinyl, and benzo[1,3]dioxolyl. The phrase also includes bridged polycyclic systems containing heteroatoms, such as (but not limited to) quinuclidinyl. Representative examples of the heterocyclic group include (but are not limited to) aziridinyl, azetidinyl, azepanyl, oxetanyl, pyrrolidinyl, imidazolidinyl (e.g., imidazolidin-4-one or imidazolidine-2,4-dione), pyrazolidinyl, thiazolidinyl, tetrahydrothienyl, tetrahydrofuryl, dioxolyl, furyl, thienyl, pyrrolyl, pyrrolinyl, imidazolyl, imidazolinyl, pyrazolyl, pyrazolinyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, benzisoxazolyl (e.g., benzo[d]isoxazolyl), thiazolyl, thiazolinyl, isothiazolyl, thiadiazolyl, oxadiazolyl, piperidinyl, piperazinyl (e.g., piperazin-2-one), morpholinyl, thiomorpholinyl, tetrahydropyranyl (e.g., tetrahydro-2H-pyranyl), tetrahydrothiopyranyl, oxathianyl, dioxyl, dithianyl, pyranyl, pyridyl, pyrimidinyl, piperazinyl, pyrazinyl, triazinyl, dihydropyridyl, dihydrodithiazinyl, dihydrodithionyl, 1,4-dioxaspiro[4.5]decyl, homopiperazinyl, quinuclidinyl, indolyl (e.g., indol-2-one), isoindolin-1-one, indolinyl, isoindolyl, isoindolinyl, azaindolyl, pyrrolo-pyridyl (e.g., 1H-pyrrolo[2,3-b]pyridyl), indazolyl, ind yl, benzotriazolyl (e.g., 1H-benzo[d][1,2,3]triazolyl), benzimidazolyl (e.g., 1H-benzo[d]imidazolyl or 1H-benzo[d]imidazol-2(3H)-onyl), benzofuranyl, benzothiophenyl, benzothiazolyl, benzodiazolyl, benzothiazolyl, benzodithiazolyl, benzo ... 1H-pyrazolo[3,4-b]pyridinyl, 1H-pyrazolo[4,3-b]pyridinyl, ...3,4-b]pyridinyl, 1H-pyrazolo[3,4-b]pyridinyl, 1H-pyrazolo[3,4-b]pyridinyl, 1H-pyrazolo[3,4-b]pyridinyl, 1H-pyrazolo[3,4-b]pyridinyl, 1H-pyrazolo[3,4-b]pyridin For example, 1H-imidazo[4,5-b]pyridinyl), triazolopyridinyl, isoazolopyridinyl, purinyl, xanthinyl, adeninyl, guaninyl, quinolyl, isoquinolyl, 3,4-dihydroisoquinolin-1(2H)-one, quininyl, quinoxaline, quinazolinyl, ox ... dihydrobenzothiazinyl, dihydrobenzofuranyl, dihydroindolyl, dihydrobenzodioxadienyl, tetrahydroindolyl, tetrahydroindazolyl, tetrahydrobenzimidazolyl, tetrahydrobenzotriazolyl, tetrahydropyrrolopyridinyl, tetrahydropyrazolopyridinyl, tetrahydroimidazopyridinyl, tetrahydrotriazolopyridinyl, tetrahydropyrimidin-2(1H)-one and tetrahydroquinolinyl. Representative non-aromatic heterocyclic groups do not include fused ring species including fused aromatic groups. Examples of non-aromatic heterocyclic groups include aziridinyl, azetidinyl, azetidinyl, pyrrolidinyl, imidazolidinyl (e.g., imidazolidin-4-one or imidazolidin-2,4-dione), pyrazolidinyl, thiazolidinyl, tetrahydrothienyl, tetrahydrofuranyl, piperidinyl, piperonyl (e.g., piperonyl-2-one), oxazolidinyl, thioxazolidinyl, tetrahydropyranyl (e.g., tetrahydro-2H-pyranyl), tetrahydrothiopyranyl, oxathiohexanyl, dithianyl, 1,4-dioxaspiro[4.5]decyl, homopiperidinyl, quininyl, or tetrahydropyrimidin-2(1H)-one. Representative substituted heterocyclic groups may be monosubstituted or substituted more than once, such as, but not limited to, pyridyl or oxazolidinyl, which are 2-substituted, 3-substituted, 4-substituted, 5-substituted, or 6-substituted or disubstituted with various substituents such as those listed below. As used herein and unless otherwise specified, "cycloalkylalkyl" is a radical having the formula -alkyl-cycloalkyl, where alkyl and cycloalkyl are defined above. Substituted cycloalkylalkyl may be substituted on the alkyl, cycloalkyl, or both the alkyl and cycloalkyl portions of the radical. Representative cycloalkylalkyl radicals include, but are not limited to, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cyclopropylethyl, cyclobutylethyl, cyclopentylethyl, cyclohexylethyl, cyclopentylpropyl, cyclohexylpropyl, and the like. As used herein and unless otherwise specified, "aralkyl" is a group of the formula -alkyl-aryl, where alkyl and aryl are defined above. Substituted aralkyl can be substituted on the alkyl, aryl, or both the alkyl and aryl moieties of the group. Representative aralkyls include, but are not limited to, benzyl and phenethyl, and aralkyls in which the aryl is fused to a cycloalkyl, such as indan-4-ylethyl. As used herein and unless otherwise specified, "heterocyclylalkyl" is a group of the formula -alkyl-heterocyclyl, where alkyl and heterocyclyl are defined above. "Heteroarylalkyl" is a group of the formula -alkyl-heteroaryl, where alkyl and heteroaryl are defined above. "Heterocycloalkylalkyl" is a group of the formula -alkyl-heterocycloalkyl, where alkyl and heterocycloalkyl are defined above. Substituted heterocyclylalkyl can be substituted on the alkyl, heterocyclyl, or both the alkyl and heterocyclyl moieties of the group. Representative heterocyclylalkyls include, but are not limited to, quinolin-4-ylethyl, quinolin-4-ylpropyl, furan-2-ylmethyl, furan-3-ylmethyl, pyridin-3-ylmethyl, tetrahydrofuran-2-ylethyl, and indol-2-ylpropyl. As used herein and unless otherwise specified, "halogen" is fluorine, chlorine, bromine, or iodine. As used herein and unless otherwise specified, "hydroxyalkyl" is an alkyl as described above substituted with one or more hydroxyl groups. As used herein and unless otherwise specified, "alkoxy" is -O-(alkyl), where alkyl is defined above. "Alkylthio" is -S-(alkyl), where alkyl is defined above. As used herein and unless otherwise specified, "alkoxyalkyl" is -(alkyl)-O-(alkyl), where alkyl is defined above. As used herein and unless otherwise specified, "cycloalkyloxy" is -O-(cycloalkyl), where cycloalkyl is defined above. As used herein and unless otherwise specified, "aryloxy" is -O-(aryl), where aryl is defined above. As used herein and unless otherwise specified, "heterocyclyloxy" is -O-(heterocyclyl), where heterocyclyl is defined above. "Heteroaryloxy" is -O-(heteroaryl), where heteroaryl is defined above. "Heterocycloalkyloxy" is -O-(heterocycloalkyl), where heterocycloalkyl is defined above. As used herein and unless otherwise specified, "amino" is a group of the formula: -NH 2 、-NH(R # ) or -N(R # ) 2 , wherein each R # is independently alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclic group (e.g., heteroaryl or heterocycloalkyl), or heterocyclic group alkyl (e.g., heteroarylalkyl or heterocycloalkylalkyl) as defined above, each of which is independently substituted or unsubstituted. In one embodiment, "amino" is "alkylamino", which is a group having the formula: -NH-alkyl or -N(alkyl) 2 , wherein each alkyl is independently defined above. The terms "cycloalkylamino", "arylamino", "heterocyclic amino", "heteroarylamino", "heterocycloalkylamino" or similar groups are analogous to the description of "alkylamino" above, wherein the term "alkyl" is replaced by "cycloalkyl", "aryl", "heterocyclic group", "heteroaryl", "heterocycloalkyl" or similar groups, respectively. As used herein and unless otherwise specified, "carboxyl" is a group having the formula -C(O)OH. As used herein and unless otherwise specified, "acyl" is a group having the formula: -C(O)(R # ) or -C(O)H, wherein R # is defined above. "Formyl" is a group having the formula -C(O)H. As used herein and unless otherwise specified, "amide group" is a group having the formula: -C(O)-NH 2 , -C(O)-NH(R # ), -C(O)-N(R # ), 2 , -NH-C(O)H, -NH-C(O)-(R # ), -N(R # )-C(O)H or -N(R # )-C(O)-(R # ), wherein each R # is independently defined above. In one embodiment, "amide group" is "aminocarbonyl", which is a group having the formula: -C(O)-NH 2 , -C(O)-NH(R # ), -C(O)-N(R # ), 2 , wherein each R # is independently defined above. In one embodiment, "amido" is "acylamino", which is a group having the formula: -NH-C(O)H, -NH-C(O)-(R # ), -N(R # )-C(O)H or -N(R # )-C(O)-(R # ), wherein each R # is independently defined above. As used herein and unless otherwise specified, "sulfonamido" is a group having the formula: -NHSO 2 (R # ) or -N(R # )SO 2 (R # ), wherein each R # is defined above. As used herein and unless otherwise specified, "ester group" is a group having the formula: -C(O)-O-(R # ) or -O-C(O)-(R # ), wherein R # is defined above. In one embodiment, "ester group" is "alkoxycarbonyl", which is a group having the formula -C(O)-O-(alkyl), where alkyl is defined above. The terms "cycloalkyloxycarbonyl", "aryloxycarbonyl", "heterocyclyloxycarbonyl", "heteroaryloxycarbonyl", "heterocycloalkyloxycarbonyl" or similar groups are modeled after the description of "alkoxycarbonyl" above, where the term "alkoxy" is replaced by "cycloalkyloxy", "aryloxy", "heterocyclyloxy", "heteroaryloxy", "heterocycloalkyloxy" or similar groups, respectively. As used herein and unless otherwise specified, "carbamate group" is a group having the formula: -O-C(O)-NH 2 、-O-C(O)-NH(R # )、-O-C(O)-N(R # ) 2 、-NH-C(O)-O-(R # ) or -N(R # )-C(O)-O-(R # ),where each R # is independently defined above. As used herein and unless otherwise specified, "urea group" is a group having the formula: -NH(CO)NH 2 、-NHC(O)NH(R # )、-NHC(O)N(R # ) 2 、-N(R # )C(O)NH 2 、-N(R # )C(O)NH(R # ) or -N(R # )C(O)N(R # ) 2 ,where each R #Independently defined above. As used herein and unless otherwise specified, "sulfinyl" is a group having the formula -S(O)R # wherein R # is defined above. As used herein and unless otherwise specified, "sulfonyl" is a group having the formula -S(O) 2 R # wherein R # is defined above. As used herein and unless otherwise specified, "aminosulfonyl" is a group having the following formula: -SO 2 NH 2 -SO 2 NH(R # ) or -SO 2 N(R # ) 2 wherein each R # is independently defined above. When a group described herein other than an alkyl group is referred to as "substituted", it may be substituted with any one or more suitable substituents. Illustrative examples of substituents are: those substituents found in the exemplary compounds and examples disclosed herein, and halogen; alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclic, heteroaryl, heterocycloalkyl, cycloalkylalkyl, aralkyl, heterocycloalkylalkyl, heteroarylalkyl, heterocycloalkylalkyl which are further substituted as appropriate; hydroxy; alkoxy; cycloalkyloxy, aryloxy, heterocyclooxy, heteroaryloxy, heterocycloalkyloxy, cycloalkylalkoxy, aralkyloxy, heterocycloalkyloxy, heteroarylalkyloxy, heterocycloalkylalkyloxy; oxo(=O); oxide (for example, a nitrogen atom substituted with an oxide is referred to as an N-oxide); amino, alkylamino, cycloalkylamino, arylamino, heterocycloamino, heteroarylamino, heterocycloalkylamino; imino; imido; formamidine; guanidine; enamine; amide; sulfonamido; urea, nitrourea; oxime; hydroxylamine; alkoxyamine; aralkyloxyamine; hydrazino; hydrazide; hydrazo; azido; nitro; thio(-SH), alkylthio; =S; sulfinyl; sulfonyl; aminosulfonyl; phosphonate; phosphinyl; acyl; formyl; carboxyl; ester; carbamate; amide; cyano; isocyanato; isothiocyanato; cyanato; thiocyanato; or -B(OH) 2 In some embodiments, one or more hydrogens in the substituent, such as one, two, three, four or five hydrogens, may be replaced by halogen. In some embodiments, the hydrogen atom is replaced with an alkyl, alkoxy, aryloxy, halogen or haloalkyl for substitution. As used herein, the term "hemoglobinopathy" or "hemoglobinopathies" means any disease or disorder that affects red blood cells. Hemoglobinopathies include (but are not limited to) sickle cell disease and anemia. As used herein, the term "HbF" means fetal hemoglobin. As used herein, the term "gene therapy" means treating a disease or disorder by transferring genetic material into cells or bringing genetic material into contact with cells. As used herein, the term "CRISPR" means clustered regularly interspaced short palindromic repeats. As used herein, the term "pharmaceutically acceptable salt" refers to salts prepared from pharmaceutically acceptable non-toxic acids or bases (including inorganic and organic acids and bases). Suitable pharmaceutically acceptable base addition salts of the compounds of formula (I), formula (I'), formula (II), formula (II'), formula (III) and Table 1 include, but are not limited to: metal salts prepared from aluminum, calcium, lithium, magnesium, potassium, sodium and zinc; or organic salts prepared from lysine, N,N'-dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, ethylenediamine, glucosamine (N-methyl-glucosamine) and procaine. Suitable non-toxic acids include, but are not limited to, inorganic and organic acids such as acetic acid, alginic acid, anthranilic acid, benzenesulfonic acid, benzoic acid, camphorsulfonic acid, citric acid, ethanesulfonic acid, formic acid, fumaric acid, furoic acid, galacturonic acid, gluconic acid, glucuronic acid, glutamic acid, glycolic acid, hydrobromic acid, hydrochloric acid, hydroxyethanesulfonic acid, lactic acid, maleic acid, malic acid, mandelic acid, methanesulfonic acid, mucic acid, nitric acid, pamoic acid, pantothenic acid, phenylacetic acid, phosphoric acid, propionic acid, salicylic acid, stearic acid, succinic acid, sulfanilic acid, sulfuric acid, tartaric acid and p-toluenesulfonic acid. Specific non-toxic acids include hydrochloric acid, hydrobromic acid, maleic acid, phosphoric acid, sulfuric acid and methanesulfonic acid. Thus, examples of specific salts include hydrochloride and mesylate. Others are well known in the art, see, for example Remington's Pharmaceutical Sciences, 18th Edition, Mack Publishing, Easton PA (1990) or Remington: The Science and Practice of Pharmacy, 19th Edition, Mack Publishing, Easton PA (1995). As used herein and unless otherwise indicated, the term "stereoisomer" or "stereoisomerically pure" means a stereoisomer of a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III) or Table 1, which substantially does not contain other stereoisomers of the compound. For example, a stereoisomerically pure compound having one chiral center substantially does not contain the opposite enantiomer of the compound. A stereoisomerically pure compound having two chiral centers will substantially not contain other diastereomers of the compound. Typical stereoisomerically pure compounds comprise more than about 80% by weight of one stereoisomer of the compound and less than about 20% by weight of other stereoisomers of the compound, more than about 90% by weight of one stereoisomer of the compound and less than about 10% by weight of other stereoisomers of the compound, more than about 95% by weight of one stereoisomer of the compound and less than about 5% by weight of other stereoisomers of the compound, or more than about 97% by weight of one stereoisomer of the compound and less than about 3% by weight of other stereoisomers of the compound. The compounds of formula (I), formula (I'), formula (II), formula (II'), formula (III) or Table 1 may have chiral centers and may exist in the form of racemates, individual enantiomers or diastereomers and mixtures thereof. All such isomeric forms are included in the embodiments disclosed herein, including mixtures thereof. The embodiments disclosed herein encompass the use of stereoisomerically pure forms of the compounds of formula (I), formula (I'), formula (II), formula (II'), formula (III) and those included in Table 1 and the use of mixtures of those forms. For example, mixtures comprising equal or unequal amounts of enantiomers of a particular compound of formula (I), formula (I'), formula (II), formula (II'), formula (III) or Table 1 can be used in the methods and compositions disclosed herein. These isomers can be resolved by asymmetric synthesis or using standard techniques such as chiral columns or chiral resolving agents. See, e.g., Jacques, J. et al., Enantiomers, Racemates and Resolutions (Wiley-Interscience, New York, 1981); Wilen, S. H. et al., Tetrahedron 33:2725 (1977); Eliel, E. L., Stereochemistry of Carbon Compounds (McGraw-Hill, NY, 1962); and Wilen, S. H., Tables of Resolving Agents and Optical Resolutions, page 268 (edited by E.L. Eliel, Univ. of Notre Dame Press, Notre Dame, IN, 1972). It should also be noted that the compounds of formula (I), formula (I'), formula (II), formula (II'), formula (III) or in Table 1 may include E and Z isomers or mixtures thereof, as well as cis and trans isomers or mixtures thereof. In certain embodiments, the compounds of formula (I), formula (I'), formula (II), formula (II'), formula (III) or in Table 1 are separated in the form of E or Z isomers. In other embodiments, the compounds of formula (I), formula (I'), formula (II), formula (II'), formula (III) or in Table 1 are mixtures of E and Z isomers. "Tautomers" refer to isomeric forms of a compound that are in equilibrium with each other via proton migration. The concentrations of the isomeric forms will depend on the environment in which the compound is present and can vary, for example, depending on whether the compound is a solid or in an organic or aqueous solution. For example, in an aqueous solution, pyrazole can exist in the following isomeric forms, which are referred to as tautomers of each other: As will be readily understood by those skilled in the art, a wide variety of functional groups and other structures can exhibit tautomerism, and all tautomers of the compounds of formula (I), formula (I'), formula (II), formula (II'), formula (III) or in Table 1 are within the scope of the present invention. It should also be noted that the compounds of formula (I), formula (I'), formula (II), formula (II'), formula (III) or in Table 1 may contain an unnatural proportion of atomic isotopes of at least one atom. For example, the compound can be radiolabeled with a radioactive isotope such as tritium ( 3 H), iodine-125 ( 125 I), sulfur-35 ( 35 S) or carbon-14 ( 14 C), or can be isotope-enriched, such as with carbon-13 ( 13 C) or nitrogen-15 ( 15N) Enrichment. As used herein, an "isotopologue" is a compound that has been isotopically enriched. The term "isotopically enriched" means that an atom has an isotopic composition that is different from the natural isotopic composition of that atom. "Isotopically enriched" can also mean that a compound contains at least one atom having an isotopic composition that is different from the natural isotopic composition of that atom. The term "isotopic composition" means the amounts of the various isotopes present for a given atom. Radioactively labeled and isotopically enriched compounds are suitable as therapeutic agents (e.g., cancer and inflammation therapeutic agents), research reagents (e.g., binding assay reagents), and diagnostic agents (e.g., in vivo imaging agents). All isotopic variants of the compounds of formula (I), formula (I'), formula (II), formula (II'), formula (III), or Table 1 described herein, whether radioactive or not, are intended to be encompassed within the scope of the examples provided herein. In some embodiments, isotopologues of the compounds of formula (I), formula (I'), formula (II), formula (II'), formula (III), or Table 1 are provided, such as those isotopologues being carbon-13 or nitrogen-15 enriched compounds of formula (I), formula (I'), formula (II), formula (II'), formula (III), or Table 1. As used herein, "deuterated" means a compound in which at least one hydrogen (H) has been replaced by deuterium (represented by D or 2 H), i.e., the compound is enriched in deuterium at at least one position. It should be noted that if there is an inconsistency between the depicted structure and the name of that structure, more consideration is given to the depicted structure. As used herein, "treatment" means the complete or partial alleviation of a disorder, disease, or condition, or one or more symptoms associated with a disorder, disease, or condition, or the slowing or prevention of the further progression or worsening of such symptoms, or the alleviation or eradication of one or more causes of the disorder, disease, or condition itself. In one embodiment, the disorder, condition, or disease is a hemoglobinopathy. As used herein, "prevention" means a method of delaying and / or preventing the full or partial onset, recurrence, or spread of a disorder, disease, or condition; preventing an individual from contracting a disorder, disease, or condition; or reducing the risk of an individual contracting a disorder, disease, or condition. In one embodiment, the disorder, condition, or disease is a hemoglobinopathy. The term "effective amount" in connection with a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III), or Table 1 means an amount that is capable of treating or preventing a disorder, disease, or condition, or its symptoms, as disclosed herein. In one embodiment, the disorder, condition, or disease is a hemoglobinopathy. The term "individual" or "patient" includes humans. The term "combination" or "administered in combination" includes administration in the form of a mixture, simultaneous administration using separate formulations, and sequential administration in any order. Unless otherwise defined, the technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art to which this application pertains. Compound The present invention provides a compound having the following formula (I): Wherein: is a single bond or a double bond; A 1 is NR 1 , O, CH(R 2 ) or C(R 2 ) 2 ; A 2 is NR 1 , C=O, CH(R 2 ) or C(R 2 ) 2 ; A 3 is NR 1 , O, CH(R 2 ) or C(R 2 ) 2 ; Each R 1 is independently absent, H, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclic group, or substituted or unsubstituted heterocyclic alkyl; Each R 2 is independently absent, H, amine, or substituted or unsubstituted alkyl; Each R 3 is independently H, substituted or unsubstituted cycloalkyl, -O-R 4 , CH 2 -R', substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclic group, or substituted 3,4-dihydro-2(1H)-quinolinone; R 4is a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl; R' is a cycloalkyl; and Q is H or CH 3 。 The present invention provides a compound of formula (I) having the following formula (I'): (I') and its pharmaceutically acceptable salts, tautomers, isotopologues and stereoisomers, wherein: is a single bond or a double bond; A 1' is NR 1' 、O or CH(R 2' ); A 2' is NR 1' 、C=O、CR 2' or CH(R 2' ); A 3' is NR 1' 、O、CR 2' or CH(R 2' ); Each R 1' is independently absent, H, a substituted or unsubstituted alkyl, a substituted or unsubstituted cycloalkyl, or a substituted or unsubstituted heterocyclic alkyl; Each R 2' is independently H, an amine, or a substituted or unsubstituted alkyl; Each R 3' is independently H, a substituted or unsubstituted cycloalkyl, -O-R 4' 、CH 2 -R*, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, or a substituted 3,4-dihydro-2(1H)-quinolinone; R 4' is a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl; R* is a cycloalkyl; and Q* is H or CH 3 。 In certain embodiments, is a single bond. In some embodiments, is a double bond. In some embodiments, A 1' is NR 1 . In some embodiments, A 1 is NR 1 . In some embodiments, A 2' is NR 1 . In some embodiments, A 2 is NR 1 . In some embodiments, A 3' is NR 1 . In some embodiments, A 3 is NR 1 . In some embodiments, R 1' is CH 3 . In some embodiments, R 1 is CH 3 . In some embodiments, A 2' is CR 2' . In some embodiments, A 2 is CR 2' . In some embodiments, R 2' is H. In some embodiments, R 2 is H. In some embodiments, R 2' is CH 3 . In some embodiments, R 2 is CH 3 。 In certain embodiments, R 3' is CH 2 -R*, and R* is a substituted or unsubstituted C 1 -C 6 alkyl, or a substituted or unsubstituted C 3 -C 6 cycloalkyl. In certain embodiments, R 3 is CH 2 -R', and R' is a substituted or unsubstituted C 1 -C 6 alkyl, or a substituted or unsubstituted C 3 -C 6 cycloalkyl. In certain embodiments, R 3 is , , , , , , , , , , , , , , , , , or 。 In certain embodiments, R* is cyclopropyl. In certain embodiments, R' is cyclopropyl. In certain embodiments, R 3' is: , wherein: R 5'is H, a substituted or unsubstituted alkyl group, or an alkoxy group; and R 6' is H, a halogen, or a substituted or unsubstituted alkyl group. In certain embodiments, R 3 is: , where: R 5 is H, a substituted or unsubstituted alkyl group, or an alkoxy group; and R 6 is H, a halogen, or a substituted or unsubstituted alkyl group. In certain embodiments, R 5' is CH 3 . In certain embodiments, R 5 is CH 3 . In certain embodiments, R 6' is a haloalkyl group. In certain embodiments, R 6 is a haloalkyl group. In certain embodiments, is , , , , , , , or . Provided herein are compounds of formula (I) selected from: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , or a pharmaceutically acceptable salt, tautomer, isotopologue or stereoisomer thereof. The present invention provides a compound having the following formula (II): (II) and pharmaceutically acceptable salts, tautomers, isotopologues and stereoisomers thereof, wherein: Q' is H or CH 3 ; Y is CR 13 , CH or N; R 7 is H, O-R 9 , substituted or unsubstituted aryl, or substituted or unsubstituted alkyl, R 8 is H, O-R 10 , or substituted or unsubstituted aryl; R 9 is substituted or unsubstituted alkyl, aryl, CH 2 CH 2 N(CH 3 ) 2 or CH 2 CH 2 -R 11 ; R 10 is substituted or unsubstituted alkyl, or substituted or unsubstituted aryl; R 11 is piperidinyl; and R 13 is substituted or unsubstituted alkyl. The present invention provides a compound of formula (II) having the following formula (II'): (II') and its pharmaceutically acceptable salts, tautomers, isotopologues and stereoisomers, wherein: Q** is H or CH 3 ; Y' is CH or N; R 7' is H, O-R 9' , substituted or unsubstituted aryl, or substituted or unsubstituted alkyl, R 8' is H, O-R 10' , or substituted or unsubstituted aryl; R 9' is substituted or unsubstituted alkyl, aryl, CH 2 CH 2 N(CH 3 ) 2 or CH 2 CH 2 -R 11' ; R 10' is substituted or unsubstituted alkyl, or substituted or unsubstituted aryl; and R 11' is piperidinyl. In certain embodiments, Y is CH. In certain embodiments, Y' is CH. In certain embodiments, Y is N. In certain embodiments, Y' is N. In certain embodiments, R 7 is CH 3 . In certain embodiments, R 7' is CH 3 . In certain embodiments, R 10 is CH 3 . In certain embodiments, R 10' is CH 3 . In certain embodiments, R 10 is an aryl. In certain embodiments, R 10' is an aryl. In certain embodiments, R 10 is a phenyl. In certain embodiments, R 10' is a phenyl. In certain embodiments, R 10 is a substituted phenyl. In certain embodiments, R 10' is a substituted phenyl. In certain embodiments, R 13 is a C 1 -C 6 alkyl substituted with an aryloxy. Provided herein are compounds of formula (II) selected from: , , , , , or a pharmaceutically acceptable salt, tautomer, isotopologue or stereoisomer thereof. Provided herein are compounds having the following formula (III): (III) and pharmaceutically acceptable salts, tautomers, isotopologues and stereoisomers thereof, wherein: Q'' is H or CH 3 ; R 12 is a substituted or unsubstituted pyridyl, substituted or unsubstituted alkyl, substituted or unsubstituted heterocyclic group, or substituted or unsubstituted C 3 -C 6 cycloalkyl. In certain embodiments, Q'' is H. In certain embodiments, Q'' is CH 3 . In certain embodiments, R 12 is CH 3 . In certain embodiments, R 12 is cyclopropyl. In certain embodiments, R 12 is selected from substituted or unsubstituted thiazole, or substituted or unsubstituted pyrazole. In certain embodiments, R 12 is: , where Q 3 is selected from H, Cl, or F; Q 4 is selected from H, CH 3 or CH(F) 2 ; Q 5 is selected from H, CH 3 or OCH 3 ; and Q 6 is selected from H or F. In certain embodiments, Q 3 is F. In certain embodiments, Q 5 is OCH 3 . In certain embodiments, Q 5 is CH 3 . In certain embodiments, Q 3 is H, Q 4 is H, Q 5 is CH 3 , and Q 6 is H. In certain embodiments, Q 3 is H, Q 4 is CH(F) 2 , Q 5 is H, and Q 6 is H. In certain embodiments, Q 3 is F, Q 4 is CH 3 , Q 5 is H, and Q 6 is H. In certain embodiments, Q 3 is F, Q 4 is H, Q 5 is CH 3 , and Q 6 is H. In certain embodiments, Q 3 is Cl, Q 4 is CH 3 , Q 5 is H, and Q 6 is H. In certain embodiments, Q 3 is H, Q 4 is CH 3 , Q 5 is CH 3 , and Q 6 is H. In certain embodiments, Q 3 is H, Q 4 is CH 3 , Q 5 is OCH 3 , and Q 6is H. In certain embodiments, Q 3 is F, Q 4 is H, Q 5 is OCH 3 , and Q 6 is H. In certain embodiments, Q 3 is F, Q 4 is OCH3 3 , Q 5 is H, and Q 6 is H. Provided herein are compounds of formula (III) selected from: , , , , , , , , , , , , , , , , , or a pharmaceutically acceptable salt, tautomer, isotopologue or stereoisomer thereof. In some embodiments, the compound is selected from: 4-((1,2-dimethyl-5-(2-methylpyridin-4-yl)-1H-benzo[d]imidazol-6-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-((1-cyclopropyl-5-(2-methylpyridin-4-yl)-1H-benzo[d]imidazol-6-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-((1,3-dimethyl-6-(2-methylpyridin-4-yl)-1H-indazol-5-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((6-(2-methylpyridin-4-yl)-1-(tetrahydro-2H-pyran-4-yl)-1H-indazol-5-yl)amino)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((5-(3-fluoro-4-methoxyphenyl)-1-methyl-1H-benzo[d]imidazol-6-yl)amino)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((5-(2-fluoro-6-methylphenoxy)-1-methyl-1H-indazol-4-yl)amino)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((1-methyl-5-(2-methylpyridin-4-yl)-1H-indazol-6-yl)amino)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((3-methyl-6-(2-methylpyridin-4-yl)benzo[d]isoxazol-5-yl)amino)isoindoline-1,3-dione; 4-((6-(2-(dimethylamino)ethoxy)-4-phenoxypyridin-3-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-((6-cyclopropyl-1-(tetrahydro-2H-pyran-4-yl)-1H-indazol-5-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-((6-(2-(difluoromethyl)pyridin-4-yl)-1-(tetrahydro-2H-pyran-4-yl)-1H-indazol-5-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((2-methoxy-4-(2-(piperidin-1-yl)ethoxy)phenyl)amino)isoindoline-1,3-dione;4-((5-(2-chlorophenoxy)-1-(tetrahydro-2H-pyran-4-yl)-1H-indazol-4-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((6-(3-fluoro-4-methoxyphenyl)-1-methyl-1H-indazol-5-yl)amino)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((1-methyl-6-phenoxy-1H-indazol-5-yl)amino)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((6-(3-fluorophenoxy)-1-(tetrahydro-2H-pyran-4-yl)-1H-indazol-5-yl)amino)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((6-(4-fluorophenoxy)-1-methyl-1H-indazol-5-yl)amino)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((6-methoxy-1-(tetrahydro-2H-pyran-4-yl)-1H-indazol-5-yl)amino)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((1-methyl-6-(2-methylpyridin-4-yl)-1H-indazol-5-yl)amino)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((4-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-indazol-5-yl)amino)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((6-methyl-4-phenoxypyridin-3-yl)amino)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((1-methyl-6-(tetrahydro-2H-pyran-4-yl)-1H-indazol-5-yl)amino)isoindoline-1,3-dione; 4-((1,2-dimethyl-6-(2-methylpyridin-4-yl)-1H-benzo[d]imidazol-5-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((1-methyl-6-(6-methylpyridin-4-yl)-1H-indazol-5-yl)amino)isoindoline-1,3-dione; 4-((6-(3-chlorophenoxy)-1-methyl-1H-indazol-5-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((1-methyl-5-((4-methylpyrimidin-5-yl)oxy)-1H-indazol-4-yl)amino)isoindoline-1,3-dione;2-(2,6-Dioxopiperidin-3-yl)-4-((1-methyl-5-phenoxy-1H-indazol-6-yl)amino)isoindoline-1,3-dione; 2-(2,6-Dioxopiperidin-3-yl)-4-((1-methyl-6-(3-(trifluoromethyl)phenyl)-1H-indazol-5-yl)amino)isoindoline-1,3-dione; 4-((6-(2,3-Dimethylpyridin-4-yl)-1-methyl-1H-indazol-5-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-Dioxopiperidin-3-yl)-4-((6-methoxy-4-phenylpyridin-3-yl)amino)isoindoline-1,3-dione; 4-((3-(Dimethylamino)-2,3-dihydro-1H-inden-5-yl)amino)-2-((S)-3-methyl-2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; (S)-2-(2,6-Dioxopiperidin-3-yl)-4-((1-methyl-6-(2-methylpyridin-4-yl)-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)isoindoline-1,3-dione; 4-((1,6-Dimethyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-((6-Cyclopropyl-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; (S)-4-((6-(1,5-Dimethyl-6-oxo-1,6-dihydropyridin-3-yl)-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-Dioxopiperidin-3-yl)-4-((1-methyl-6-(1-methyl-1H-pyrazol-4-yl)-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)isoindoline-1,3-dione; (S)-4-((6-(1-Cyclopropyl-1H-pyrazol-4-yl)-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; (S)-4-((6-(1,3-Dimethyl-1H-pyrazol-4-yl)-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;2-(2,6-Dioxopiperidin-3-yl)-4-((1-methyl-6-(4-methylthiazol-2-yl)-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)isoindoline-1,3-dione; (S)-4-((6-(2,6-dimethylpyridin-4-yl)-1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; (S)-4-((1,3-dimethyl-6-(2-methylpyridin-4-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; (S)-2-(2,6-dioxopiperidin-3-yl)-4-((1-methyl-6-(2-methylpyridin-4-yl)-1H-indazol-5-yl)amino)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((1-methyl-6-(2-methylpyridin-4-yl)-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)isoindoline-1,3-dione; 2-((S)-2,6-dioxopiperidin-3-yl)-4-((6-(2-methylpyridin-4-yl)-1-((R)-tetrahydrofuran-3-yl)-1H-indazol-5-yl)amino)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((6-(3-fluoro-2-methylpyridin-4-yl)-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((6-(5-fluoro-2-methylpyridin-4-yl)-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)isoindoline-1,3-dione; 4-((6-(3-chloro-2-methylpyridin-4-yl)-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-((6-(2,6-dimethylpyridin-4-yl)-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; (S)-2-(2,6-dioxopiperidin-3-yl)-4-((6-(2-methoxy-6-methylpyridin-4-yl)-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)isoindoline-1,3-dione;2-(2,6-Dioxopiperidin-3-yl)-4-((6-(3-fluoro-2-methoxypyridin-4-yl)-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)isoindoline-1,3-dione; 2-(2,6-Dioxopiperidin-3-yl)-4-((6-(5-fluoro-2-methoxypyridin-4-yl)-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)isoindoline-1,3-dione; 2-((R)-2,6-Dioxopiperidin-3-yl)-4-((6-(2-methylpyridin-4-yl)-1-((R)-tetrahydrofuran-3-yl)-1H-indazol-5-yl)amino)isoindoline-1,3-dione; (R)-2-(3-Methyl-2,6-dioxopiperidin-3-yl)-4-((1-methyl-6-(2-methylpyridin-4-yl)-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)isoindoline-1,3-dione; 2-(3-Methyl-2,6-dioxopiperidin-3-yl)-4-((3-(phenoxymethyl)phenyl)amino)isoindoline-1,3-dione, or a pharmaceutically acceptable salt, tautomer, isotopologue, and / or stereoisomer thereof. In certain embodiments, the compound is 4-((1,2-Dimethyl-5-(2-methylpyridin-4-yl)-1H-benzo[d]imidazol-6-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione, or a pharmaceutically acceptable salt, tautomer, isotopologue, and / or stereoisomer thereof. In certain embodiments, the compound is 4-((1-Cyclopropyl-5-(2-methylpyridin-4-yl)-1H-benzo[d]imidazol-6-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione, or a pharmaceutically acceptable salt, tautomer, isotopologue, and / or stereoisomer thereof. In certain embodiments, the compound is 4-((1,3-Dimethyl-6-(2-methylpyridin-4-yl)-1H-indazol-5-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione, or a pharmaceutically acceptable salt, tautomer, isotopologue, and / or stereoisomer thereof. In certain embodiments, the compound is 2-(2,6-Dioxopiperidin-3-yl)-4-((6-(2-methylpyridin-4-yl)-1-(tetrahydro-2H-pyran-4-yl)-1H-indazol-5-yl)amino)isoindoline-1,3-dione, or a pharmaceutically acceptable salt, tautomer, isotopologue, and / or stereoisomer thereof. In certain embodiments, the compound is 2-(2,6-dioxopiperidin-3-yl)-4-((5-(3-fluoro-4-methoxyphenyl)-1-methyl-1H-benzo[d]imidazol-6-yl)amino)isoindoline-1,3-dione, or a pharmaceutically acceptable salt, tautomer, isotopologue, and / or stereoisomer thereof. In certain embodiments, the compound is 2-(2,6-dioxopiperidin-3-yl)-4-((5-(2-fluoro-6-methylphenoxy)-1-methyl-1H-indazol-4-yl)amino)isoindoline-1,3-dione. In certain embodiments, the compound is 2-(2,6-dioxopiperidin-3-yl)-4-((1-methyl-5-(2-methylpyridin-4-yl)-1H-indazol-6-yl)amino)isoindoline-1,3-dione, or a pharmaceutically acceptable salt, tautomer, isotopologue, and / or stereoisomer thereof. In certain embodiments, the compound is 2-(2,6-dioxopiperidin-3-yl)-4-((3-methyl-6-(2-methylpyridin-4-yl)benzo[d]isoxazol-5-yl)amino)isoindoline-1,3-dione. In certain embodiments, the compound is 4-((6-(2-(dimethylamino)ethoxy)-4-phenoxypyridin-3-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione, or a pharmaceutically acceptable salt, tautomer, isotopologue, and / or stereoisomer thereof. In certain embodiments, the compound is 4-((6-cyclopropyl-1-(tetrahydro-2H-pyran-4-yl)-1H-indazol-5-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione, or a pharmaceutically acceptable salt, tautomer, isotopologue, and / or stereoisomer thereof. In certain embodiments, the compound is 4-((6-(2-(difluoromethyl)pyridin-4-yl)-1-(tetrahydro-2H-pyran-4-yl)-1H-indazol-5-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione, or a pharmaceutically acceptable salt, tautomer, isotopologue, and / or stereoisomer thereof. In certain embodiments, the compound is 2-(2,6-dioxopiperidin-3-yl)-4-((2-methoxy-4-(2-(piperidin-1-yl)ethoxy)phenyl)amino)isoindoline-1,3-dione, or a pharmaceutically acceptable salt, tautomer, isotopologue, and / or stereoisomer thereof. In certain embodiments, the compound is 4-((5-(2-chlorophenoxy)-1-(tetrahydro-2H-pyran-4-yl)-1H-indazol-4-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione, or a pharmaceutically acceptable salt, tautomer, isotopologue, and / or stereoisomer thereof. In certain embodiments, the compound is 4-((5-(2-chlorophenoxy)-1-(tetrahydro-2H-pyran-4-yl)-1H-indazol-4-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione, or a pharmaceutically acceptable salt, tautomer, isotopologue, and / or stereoisomer thereof. In certain embodiments, the compound is (S)-2-(2,6-dioxopiperidin-3-yl)-4-((1-methyl-6-(2-methylpyridin-4-yl)-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)isoindoline-1,3-dione. In certain embodiments, the compound is 2-(2,6-dioxopiperidin-3-yl)-4-((6-(3-fluoro-4-methoxyphenyl)-1-methyl-1H-indazol-5-yl)amino)isoindoline-1,3-dione, or a pharmaceutically acceptable salt, tautomer, isotopologue, and / or stereoisomer thereof. In certain embodiments, the compound is 2-(2,6-dioxopiperidin-3-yl)-4-((1-methyl-6-(2-methylpyridin-4-yl)-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)isoindoline-1,3-dione. In some embodiments, the present invention provides a pharmaceutical composition comprising an effective amount of a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III), a compound of Table 1, or a pharmaceutically acceptable salt, tautomer, isotopologue, or stereoisomer thereof, and a pharmaceutically acceptable carrier, excipient, or vehicle. Representative compounds of formula (I), formula (I'), formula (II), formula (II'), and formula (III) are set forth in Table 1. Method of Use In some embodiments, the present invention provides a method of inducing HbF expression in a cell, comprising contacting the cell with a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III), a compound of Table 1, or a pharmaceutically acceptable salt, tautomer, isotopologue, or stereoisomer thereof. In some embodiments, the present invention provides a method for reducing the expression of WIZ in a cell, which comprises contacting the cell with a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III), the compounds of Table 1 or a pharmaceutically acceptable salt, tautomer, isotopologue or stereoisomer thereof. In some embodiments, the present invention provides a method for reducing the expression of ZBTB7A in a cell, which comprises contacting the cell with a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III), the compounds of Table 1 or a pharmaceutically acceptable salt, tautomer, isotopologue or stereoisomer thereof. In some embodiments, the present invention provides a method for inducing the expression of HbF in a cell, and / or reducing the expression of ZBTB7A in a cell, and / or reducing the expression of WIZ in a cell, which comprises contacting the cell with a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III), the compounds of Table 1 or a pharmaceutically acceptable salt, tautomer, isotopologue or stereoisomer thereof. In some embodiments, the present invention provides a method for treating hemoglobinopathies, which comprises administering to an individual in need thereof a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III), the compounds of Table 1 or a pharmaceutically acceptable salt, tautomer, isotopologue or stereoisomer thereof. In some embodiments, the present invention provides the use of a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III), the compounds of Table 1 or a pharmaceutically acceptable salt, tautomer, isotopologue or stereoisomer thereof for treating hemoglobinopathies. In certain embodiments, the hemoglobinopathy is anemia. In certain embodiments, the hemoglobinopathy is sickle cell disease. In certain embodiments, the hemoglobinopathy is thalassemia. In certain embodiments, the hemoglobinopathy is α-thalassemia. In certain embodiments, the hemoglobinopathy is β-thalassemia. In certain embodiments, the present invention provides a pharmaceutical composition comprising an effective amount of a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III) or the compounds of Table 1 or a pharmaceutically acceptable salt, tautomer, isotopologue or stereoisomer thereof and a pharmaceutically acceptable carrier, excipient or vehicle. In certain embodiments, the present invention provides a method for inducing the expression of HbF in a cell, which comprises contacting the cell with a compound of formula (I), formula (I'), formula (II), formula (III) or the compounds of Table 1. In certain embodiments, provided herein are methods of reducing the expression of WIZ (i.e., a regulator of the G9a / GLP histone methyltransferase) in a cell, which comprise contacting the cell with a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III), or Table 1. In certain embodiments, provided herein are methods of reducing the expression of ZBTB7A in a cell, which comprise contacting the cell with a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III), or Table 1. In certain embodiments, provided herein are methods of treating a hemoglobinopathy, wherein the method comprises administering to an individual in need thereof a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III), or Table 1, or a pharmaceutical composition of a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III), or Table 1. In certain embodiments, the hemoglobinopathy is anemia. In certain embodiments, the hemoglobinopathy is sickle cell disease. In certain embodiments, the hemoglobinopathy is sickle cell anemia. In certain embodiments, the hemoglobinopathy is thalassemia. In certain embodiments, the hemoglobinopathy is α-thalassemia. In certain embodiments, the hemoglobinopathy is β-thalassemia. In certain embodiments, provided herein are methods for treating hemoglobinopathies, which comprise administering to an individual in need thereof a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III), or Table 1, or a pharmaceutical composition of a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III), or Table 1, in combination with a second active agent and / or therapy. In certain embodiments, the second active agent is luspatercept. In certain embodiments, the second active agent is voxelotor. In certain embodiments, the second active agent is crizanlizumab-tmca. In certain embodiments, the second active agent is hydroxyurea. In certain embodiments, the second active agent is L-glutamine. In certain embodiments, the second active agent is etavopivat. In certain embodiments, the second active agent is mitapivat. In certain embodiments, the second active agent is osivelotor. In certain embodiments, the second active agent is inclacumab. In certain embodiments, the second therapy is blood transfusion. In certain embodiments, the second therapy is stem cell transplantation. In certain embodiments, the second therapy is bone marrow transplantation. In certain embodiments, the second therapy is gene therapy. In certain embodiments, the gene therapy is CRISPR therapy. In certain embodiments, the hemoglobinopathy is anemia. In certain embodiments, the hemoglobinopathy is sickle cell disease. In certain embodiments, the hemoglobinopathy is thalassemia. In certain embodiments, the hemoglobinopathy is α-thalassemia. In certain embodiments, the hemoglobinopathy is β-thalassemia. The compounds of formula (I), formula (I'), formula (II), formula (II'), formula (III), or Table 1 are useful as drugs for treating, preventing, or ameliorating hemoglobinopathies. The compounds provided herein are useful for treating or preventing all diseases, disorders, or conditions disclosed herein. In one aspect, provided herein is a method for treating a disease caused by a hemoglobinopathy. In certain embodiments, the compounds described herein are for use in human medical therapy, particularly for treating hemoglobinopathies. In one aspect, provided herein is a method for treating a disease caused by a hemoglobinopathy. In certain embodiments, the compounds described herein are for use in human medical therapy, particularly for treating hemoglobinopathies. In certain embodiments, the method comprises administering to an individual suffering from a disease caused by a hemoglobinopathy a therapeutically effective amount of the described compound. In one embodiment, provided herein is a method for treating or preventing a hemoglobinopathy, the method comprising administering to an individual an effective amount of a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III), or Table 1, or a pharmaceutically acceptable salt, tautomer, isotopologue, or stereoisomer thereof. In certain embodiments, the hemoglobinopathy is anemia. In certain embodiments, the hemoglobinopathy is sickle cell disease. In certain embodiments, the hemoglobinopathy is sickle cell anemia. In another aspect, provided is also a method for preventing a disease caused by a hemoglobinopathy. In certain embodiments, the compound of formula (I), formula (I'), formula (II), formula (II'), formula (III), or Table 1, or a pharmaceutically acceptable salt, tautomer, isotopologue, or stereoisomer thereof is used in human medical therapy, particularly for preventing a hemoglobinopathy. In certain embodiments, the method comprises administering to an individual a therapeutically effective amount of the compound of formula (I), formula (I'), formula (II), formula (II'), formula (III), or Table 1, or a pharmaceutically acceptable salt, tautomer, isotopologue, or stereoisomer thereof to prevent a disease caused by a hemoglobinopathy. Second active agents and therapies In one embodiment, the second active agent for use in the methods provided herein is selected from the group consisting of luspatercept, voxelotor, crisaborole, hydroxyurea, L-glutamine, itaprevir, mitaprevir, osilutor, and inotuzumab. In one embodiment, the second therapy for use in the methods provided herein is selected from the group consisting of blood transfusion, stem cell and / or bone marrow transplantation, and / or gene therapy. In certain embodiments, the gene therapy is CRISPR therapy. Treatment and / or prevention methods In one embodiment, provided herein is a method for treating a hemoglobinopathy, which comprises administering to a patient a therapeutically effective amount of a combination of a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III), or Table 1, or an enantiomer, enantiomer mixture, tautomer, isotopologue, or pharmaceutically acceptable salt thereof with a second active agent, wherein the second active agent is selected from the group consisting of luspatercept, voxelotor, crisaborole, hydroxyurea, L-glutamine, itaprevir, mitaprevir, osilutor, and inotuzumab. In one embodiment, provided herein is a method for treating hemoglobinopathies, which comprises administering to a patient a therapeutically effective amount of a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III) or Table 1, or a mirror image isomer, a mixture of mirror image isomers, a tautomer, an isotopologue or a pharmaceutically acceptable salt thereof in combination with a second therapy, wherein the second therapy is selected from the group consisting of blood transfusion, stem cell and / or bone marrow transplantation, and / or gene therapy. In certain embodiments, the gene therapy is CRISPR therapy. Pharmaceutical compositions and routes of administration Provided herein are pharmaceutical compositions, which comprise an effective amount of a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III) or Table 1 described herein and a pharmaceutically acceptable carrier, excipient or vehicle. The compound of formula (I), formula (I'), formula (II), formula (II'), formula (III) or Table 1 can be administered to an individual enterally (e.g., orally, rectally), topically or parenterally (e.g., intravenously, intramuscularly, subcutaneously) in a conventional dosage form, such as capsules, microcapsules, tablets, granules, powders, dragees, pills, suppositories, injections, suspensions, syrups, patches, creams, lotions, ointments, gels, aerosols, solutions and emulsions. Suitable formulations can be prepared by conventional methods using conventional organic or inorganic additives, such as excipients (e.g., sucrose, starch, mannitol, sorbitol, lactose, glucose, cellulose, talc, calcium phosphate or calcium carbonate), binders (e.g., cellulose, methylcellulose, hydroxymethylcellulose, polypropylpyrrolidone, polyvinylpyrrolidone, gelatin, gum arabic, polyethylene glycol, sucrose or starch), disintegrants (e.g., starch, carboxymethylcellulose, hydroxypropyl starch, low-substituted hydroxypropyl cellulose, sodium bicarbonate, calcium phosphate or calcium citrate), lubricants (e.g., magnesium stearate, light anhydrous silicic acid, talc or sodium lauryl sulfate), flavoring agents (e.g., citric acid, menthol, glycine or orange powder), preservatives (e.g., sodium benzoate, sodium bisulfite, methyl p-hydroxybenzoate or propyl p-hydroxybenzoate), stabilizers (e.g., citric acid, sodium citrate or acetic acid), suspending agents (e.g., methylcellulose, polyvinylpyrrolidone or aluminum stearate), dispersing agents (e.g., hydroxypropylmethylcellulose), diluents (e.g., water), cosolvents (e.g., propylene glycol / tetrahydrofuran polyethylene glycol ether), buffers, copolymers (e.g., poly(lactic-co-glycolic acid), i.e., PLGA) and matrix waxes (e.g., cocoa butter, white petrolatum or polyethylene glycol). The effective amount of the compound of formula (I), formula (I'), formula (II), formula (II'), formula (III) or Table 1 in the pharmaceutical composition can be at a level that will achieve the desired effect; for example, the unit dose for oral and parenteral administration is about 0.005 mg to about 20 mg per kilogram of the individual's body weight. The dosage of the compounds of formula (I), formula (I'), formula (II), formula (II'), formula (III) or Table 1 to be administered to an individual will vary quite widely and is subject to the judgment of a healthcare practitioner. Generally, the compounds of formula (I), formula (I'), formula (II), formula (II'), formula (III) or Table 1 can be administered to an individual one to four times a day at a dosage of about 0.5 mg to about 20 mg per kg of the individual's body weight, but the above dosage can be appropriately changed according to the age, weight and medical condition of the individual as well as the type of administration. In one embodiment, the dosage is about 0.1 mg to about 3 mg per kg of the individual's body weight, about 0.5 mg to about 2 mg per kg of the individual's body weight, about 1 mg to about 2 mg per kg of the individual's body weight, or about 1.5 mg to about 2 mg per kg of the individual's body weight. In one embodiment, the dosage is about 1 mg to about 3 mg per kg of the individual's body weight. In one embodiment, the dosage is about 0.5 mg to about 1 mg per kg of the individual's body weight. In one embodiment, the dosage is about 1 mg to about 2 mg per kg of the individual's body weight. In one embodiment, the dosage is about 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0 mg per kg of the individual's body weight. In one embodiment, a dosage is given once a day. In any given case, the amount of the compound of formula (I), formula (I'), formula (II), formula (II'), formula (III) or Table 1 administered will depend on factors such as the solubility of the active ingredient, the formulation used and the route of administration. In one embodiment, the administration of the local concentration provides an intracellular exposure or concentration of about 0.01 to 10 µM. In another embodiment, provided herein are methods for treating or preventing a disease or disorder, which comprise administering to an individual having a hemoglobinopathy a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III), or Table 1 at about 1 mg / day to about 1200 mg / day. In another embodiment, provided herein are methods for treating or preventing a disease or disorder, which comprise administering to an individual having a hemoglobinopathy a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III), or Table 1 at about 0.375 mg / day to about 750 mg / day, about 0.75 mg / day to about 375 mg / day, about 3.75 mg / day to about 75 mg / day, about 7.5 mg / day to about 55 mg / day, or about 18 mg / day to about 37 mg / day. In one embodiment, the method for treating a disease or disorder comprises administering to an individual having a hemoglobinopathy a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III), or Table 1 at about 0.375 mg / day to about 750 mg / day. In one embodiment, the method for treating a disease or disorder comprises administering to an individual having a hemoglobinopathy a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III), or Table 1 at about 3.75 mg / day to about 75 mg / day. In another embodiment, provided herein are unit dosage formulations which comprise a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III), or Table 1 between about 1 mg and 200 mg, between about 35 mg and about 1400 mg, between about 125 mg and about 1000 mg, between about 250 mg and about 1000 mg, or between about 500 mg and about 1000 mg. In one embodiment, the unit dosage formulation comprises a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III), or Table 1 between about 1 mg and 200 mg. In one embodiment, the unit dosage formulation comprises a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III), or Table 1 between about 35 mg and about 1400 mg. In one embodiment, the unit dosage formulation comprises a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III), or Table 1 between about 125 mg and about 1000 mg. In one embodiment, the unit dosage formulation comprises a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III), or Table 1 between about 250 mg and about 1000 mg. In one embodiment, the unit dosage formulation comprises a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III), or Table 1 between about 500 mg and about 1000 mg. In one particular embodiment, provided herein is a unit dose formulation comprising about 100 mg or 400 mg of a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III), or Table 1. In another embodiment, the present disclosure provides unit dose formulations comprising a compound of Formula (I), Formula (I'), Formula (II), Formula (II'), Formula (III) or Table 1 in an amount of 1 mg, 5 mg, 10 mg, 15 mg, 20 mg, 30 mg, 35 mg, 40 mg, 50 mg, 70 mg, 100 mg, 125 mg, 130 mg, 140 mg, 175 mg, 200 mg, 250 mg, 280 mg, 350 mg, 500 mg, 560 mg, 700 mg, 750 mg, 1000 mg or 1400 mg. In one embodiment, the unit dose formulation comprises 1 mg of a compound of Formula (I), Formula (I'), Formula (II), Formula (II'), Formula (III) or Table 1. In one embodiment, the unit dose formulation comprises 5 mg of a compound of Formula (I), Formula (I'), Formula (II), Formula (II'), Formula (III) or Table 1. In one embodiment, the unit dose formulation comprises 10 mg of a compound of Formula (I), Formula (I'), Formula (II), Formula (II'), Formula (III) or Table 1. In one embodiment, the unit dose formulation comprises 15 mg of a compound of Formula (I), Formula (I'), Formula (II), Formula (II'), Formula (III) or Table 1. In one embodiment, the unit dose formulation comprises 20 mg of a compound of Formula (I), Formula (I'), Formula (II), Formula (II'), Formula (III) or Table 1. In one embodiment, the unit dose formulation comprises 25 mg of a compound of Formula (I), Formula (I'), Formula (II), Formula (II'), Formula (III) or Table 1. In one embodiment, the unit dose formulation comprises 30 mg of a compound of Formula (I), Formula (I'), Formula (II), Formula (II'), Formula (III) or Table 1. In one embodiment, the unit dose formulation comprises 35 mg of a compound of Formula (I), Formula (I'), Formula (II), Formula (II'), Formula (III) or Table 1. In one embodiment, the unit dose formulation comprises 40 mg of a compound of Formula (I), Formula (I'), Formula (II), Formula (II'), Formula (III) or Table 1. In one embodiment, the unit dose formulation comprises 50 mg of a compound of Formula (I), Formula (I'), Formula (II), Formula (II'), Formula (III) or Table 1. In one embodiment, the unit dose formulation comprises 70 mg of a compound of Formula (I), Formula (I'), Formula (II), Formula (II'), Formula (III) or Table 1. In one embodiment, the unit dose formulation comprises 100 mg of a compound of Formula (I), Formula (I'), Formula (II), Formula (II'), Formula (III) or Table 1.In one embodiment, the unit dose formulation comprises 125 mg of a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III) or Table 1. In one embodiment, the unit dose formulation comprises 130 mg of a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III) or Table 1. In one embodiment, the unit dose formulation comprises 140 mg of a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III) or Table 1. In one embodiment, the unit dose formulation comprises 175 mg of a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III) or Table 1. In one embodiment, the unit dose formulation comprises 200 mg of a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III) or Table 1. In one embodiment, the unit dose formulation comprises 250 mg of a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III) or Table 1. In one embodiment, the unit dose formulation comprises 280 mg of a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III) or Table 1. In one embodiment, the unit dose formulation comprises 350 mg of a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III) or Table 1. In one embodiment, the unit dose formulation comprises 500 mg of a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III) or Table 1. In one embodiment, the unit dose formulation comprises 560 mg of a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III) or Table 1. In one embodiment, the unit dose formulation comprises 700 mg of a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III) or Table 1. In one embodiment, the unit dose formulation comprises 750 mg of a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III) or Table 1. In one embodiment, the unit dose formulation comprises 1000 mg of a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III) or Table 1. In one embodiment, the unit dose formulation comprises 1400 mg of a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III) or Table 1. The compounds of formula (I), formula (I'), formula (II), formula (II'), formula (III) or Table 1 can be administered once, twice, three times, four times or more times daily. In a particular embodiment, a dose of 600 mg or less is administered as a single daily dose, and a dose greater than 600 mg is administered twice daily in an amount equal to one half of the total daily dose. For convenience, the compounds of formula (I), formula (I'), formula (II), formula (II'), formula (III) or Table 1 can be administered orally. In one embodiment, when administered orally, the compounds of formula (I), formula (I'), formula (II), formula (II'), formula (III) or Table 1 are administered with food and water. In another embodiment, the compounds of formula (I), formula (I'), formula (II), formula (II'), formula (III) or Table 1 are dispersed in water or fruit juice (such as apple juice or orange juice) and administered orally as a suspension. The compounds of formula (I), formula (I'), formula (II), formula (II'), formula (III) or Table 1 can also be administered intradermally, intramuscularly, intraperitoneally, transdermally, intravenously, subcutaneously, intranasally, epidurally, sublingually, intracerebrally, intravaginally, percutaneously, rectally, transmucosally, by inhalation, topically to the ear, nose, eye or skin, or by ocular topical (i.e., subconjunctival, intravitreal, retrobulbar, intracameral) administration. The mode of administration is determined by the judgment of a health care practitioner and may in part depend on the location of the medical condition. In one embodiment, capsules are provided herein that contain a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III) or Table 1 and do not contain additional carriers, excipients or vehicles. In another embodiment, compositions are provided herein that comprise an effective amount of a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III) or Table 1 and a pharmaceutically acceptable carrier or vehicle, wherein the pharmaceutically acceptable carrier or vehicle can comprise excipients, diluents or mixtures thereof. In one embodiment, the composition is a pharmaceutical composition. The composition can be in the form of tablets, chewable tablets, capsules, solutions, parenteral solutions, troches, suppositories, suspensions, gels, rumen devices (e.g., for extended prophylaxis or controlled release), implants, topical pour-ons, transdermal delivery gels, drops, implants (including devices, gels, liquids (e.g., PLGA)), and the like. The composition can be formulated to contain the daily dose or a suitable fraction of the daily dose in a dosage unit, which can be a single tablet or capsule or a suitable volume of liquid. In one embodiment, the solution is prepared from a water-soluble salt, such as a hydrochloride. Generally, all compositions are prepared according to known methods in medicinal chemistry. Capsules can be prepared by mixing a compound of formula (I), formula (I'), formula (II), formula (II'), formula (III), or of Table 1 with a suitable carrier or diluent; and filling a suitable amount of the mixture into capsules. Common carriers and diluents include (but are not limited to) inert powdery substances, such as many different kinds of starches; powdered cellulose, especially crystalline and microcrystalline cellulose; sugars, such as fructose, mannitol, and sucrose; cereal flours, and similar edible powders. Tablets can be prepared by direct compression, wet granulation, or dry granulation. Their formulations usually incorporate a diluent, a binder, a lubricant, a disintegrant, and the compound. Typical diluents include, for example, various types of starches, lactose, mannitol, kaolin, calcium phosphate or calcium sulfate, inorganic salts (such as sodium chloride), and powdered sugar. Powdered cellulose derivatives are also suitable. Typical tablet binders are substances such as starches, gelatin, and sugars, such as lactose, fructose, glucose, and their analogs. Natural and synthetic gums are also suitable, including gum arabic, alginates, methyl cellulose, polyvinyl pyrrolidone, and the like. Polyethylene glycol, ethyl cellulose, and waxes can also serve as binders. Lubricants may be necessary for tablet formulations to prevent the tablets and punches from sticking in the die. Lubricants can be selected from smooth solids (such as talc, magnesium stearate, and calcium stearate), stearic acid, and hydrogenated vegetable oils. Tablet disintegrants are substances that swell when wetted to break the tablet and release the compound. They include starches, clays, celluloses, algins, and gums. More specifically, for example, corn starch and potato starch, methyl cellulose, agar, bentonite, wood cellulose, powdered natural sponge, cation exchange resins, alginic acid, guar gum, citrus pulp, and carboxymethyl cellulose, as well as sodium lauryl sulfate can be used. Tablets can be coated with sugar as a flavoring and sealing agent or coated with a film-forming protective agent to alter the dissolution characteristics of the tablet. The composition can also be formulated as chewable tablets, for example, by using a substance such as mannitol in the formulation. The effects of the compounds of formula (I), formula (I'), formula (II), formula (II'), formula (III) or Table 1 can be delayed or prolonged by appropriate formulations. For example, slow-dissolving pellets of the compounds of formula (I), formula (I'), formula (II), formula (II'), formula (III) or Table 1 can be prepared and incorporated into tablets or capsules, or prepared as a slow-release implantable device. The technique also includes manufacturing pellets with several different dissolution rates and filling capsules with a mixture of the pellets. The tablets or capsules can be coated with a membrane that resists dissolution for a predictable period of time. By dissolving or suspending the compounds of formula (I), formula (I'), formula (II), formula (II'), formula (III) or Table 1 in an oily or emulsified vehicle, or adding a certain amount of PLGA that slowly disperses the compound in serum, even parenteral formulations can be made into long-acting formulations. Examples of the embodiments of the present invention include: 1. A compound of formula (I): (I) and its pharmaceutically acceptable salts, tautomers, isotopologues and stereoisomers, wherein: is a single bond or a double bond; A 1 is NR 1 、O or CR 2 ; A 2 is NR 1 、C=O or CR 2 ; A 3 is NR 1 、O or CR 2 ; Each R 1 is independently absent, H, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, or substituted or unsubstituted heterocyclic alkyl; Each R 2 is independently H, amine, or substituted or unsubstituted alkyl; Each R 3 is independently H, substituted or unsubstituted alkyl, cycloalkyl, -O-R 4 、CH 2 -R', substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or substituted 3,4-dihydro-2(1H)-quinolinone; R 4 is a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl; R' is a cycloalkyl; and Q is H or CH 3 . 2. The compound according to Example 1, wherein is a single bond. 3. The compound according to Example 1, wherein is a double bond. 4. The compound according to any one of Examples 1 to 3, wherein A 1 is NR 1 . 5. The compound according to any one of Examples 1 to 4, wherein A 2 is NR 1 . 6. The compound according to any one of Examples 1 to 5, wherein A 3 is NR 1 . 7. The compound according to any one of Examples 1 to 6, wherein R 1 is CH 3 . 8. The compound according to any one of Examples 1 to 6, wherein A 2 is CR 2 . 9. The compound according to any one of Examples 1 to 8, R 2 is H. 10. The compound according to any one of Examples 1 to 8, R 2 is CH 3 . 11. The compound according to any one of Examples 1 to 10, wherein R 3 is CH 2 -R', and R' is a substituted or unsubstituted C 1 -C 6 alkyl, or a substituted or unsubstituted C 3 -C 6 cycloalkyl. 12. The compound according to Example 11, wherein R' is cyclopropyl. 13. The compound according to any one of Examples 1 to 12, wherein R 3 is: , wherein: R 5 is H, substituted or unsubstituted alkyl, or alkoxy; and R 6 is H, halogen, or substituted or unsubstituted alkyl. 14. The compound of Example 13, wherein R 5 is CH 3 . 15. The compound of any one of Examples 13 to 14, wherein R 6 is haloalkyl. 16. A compound of formula (II): (II) and its pharmaceutically acceptable salts, tautomers, isotopologues and stereoisomers, wherein: Q' is H or CH 3 ; Y is CH or N; R 7 is H, O-R 9 , substituted or unsubstituted aryl, or substituted or unsubstituted alkyl, R 8 is H, O-R 10 , or substituted or unsubstituted aryl; R 9 is substituted or unsubstituted alkyl, aryl, CH 2 CH 2 N(CH 3 ) 2 or CH 2 CH 2 -R 11 ; R 10 is substituted or unsubstituted alkyl, or substituted or unsubstituted aryl; and R 11 is piperidinyl. 17. The compound of Example 16, wherein Y is CH. 18. The compound of Example 16, wherein Y is N. 19. The compound of any one of Examples 16 to 18, wherein R 7 is CH 3 。 20. A compound according to any one of Examples 16 to 18, wherein R 10 is CH 3 。 21. A compound according to any one of Examples 16 to 18, wherein R 10 is aryl. 22. A compound according to any one of Examples 16 to 18, wherein R 10 is phenyl. 23. A compound according to any one of Examples 16 to 18, wherein R 10 is substituted phenyl. 24. A compound of formula (III): (III) and its pharmaceutically acceptable salts, tautomers, isotopologues and stereoisomers, wherein: Q'' is H or CH 3 ; R 12 is substituted or unsubstituted pyridyl, substituted or unsubstituted alkyl, substituted or unsubstituted heterocyclic group, or substituted or unsubstituted C 3 -C 6 cycloalkyl. 25. The compound according to Example 24, wherein Q'' is H. 26. The compound according to Example 24, wherein Q'' is CH 3 。 27. The compound according to any one of Examples 24 to 26, wherein R 12 is CH 3 。 28. The compound according to any one of Examples 24 to 26, wherein R 12 is cyclopropyl. 29. The compound according to any one of Examples 24 to 26, wherein R 12 is selected from substituted or unsubstituted thiazole, or substituted or unsubstituted pyrazole. 30. The compound according to any one of Examples 24 to 26, wherein R 12 is: , wherein Q 3 is selected from H, Cl or F; Q 4 is selected from H, CH 3 or CH(F) 2 ; Q 5 is selected from H, CH 3 or OCH 3 ; and Q 6 is selected from H or F. 31. The compound of Example 30, wherein Q 3 is F. 32. The compound of any one of Examples 30 to 31, wherein Q 5 is OCH 3 . 33. The compound of any one of Examples 30 to 31, wherein Q 5 is CH 3 . 34. The compound of Example 30, wherein Q 3 is H, Q 4 is H, Q 5 is CH 3 , and Q 6 is H. 35. The compound of Example 30, wherein Q 3 is H, Q 4 is CH(F) 2 , Q 5 is H, and Q 6 is H. 36. The compound of Example 30, wherein Q 3 is F, Q 4 is CH 3 , Q 5 is H, and Q 6 is H. 37. The compound of Example 30, wherein Q 3 is F, Q 4 is H, Q 5 is CH 3 , and Q 6 is H. 38. The compound of Example 30, wherein Q 3 is Cl, Q 4 is CH 3 , Q 5 is H, and Q 6 is H. 39. The compound of Example 30, wherein Q 3 is H, Q 4 is CH 3 , Q 5 is CH 3 , and Q 6 is H. 40. The compound of Example 30, wherein Q 3 is H, Q 4 is CH 3 , Q 5 is OCH 3 , and Q 6 is H. 41. The compound of Example 30, wherein Q 3 is F, Q 4 is H, Q 5 is OCH 3 , and Q 6 is H. 42. The compound of Example 30, wherein Q 3 is F, Q 4is OCH 3 , Q 5 is H, and Q 6 is H. 43. A pharmaceutical composition comprising an effective amount of a compound as described in any one of Examples 1 to 42 or a pharmaceutically acceptable salt, tautomer, isotopologue or stereoisomer thereof and a pharmaceutically acceptable carrier, excipient or vehicle. 44. A method of inducing HbF expression in a cell comprising contacting the cell with a compound or pharmaceutical composition as described in any one of Examples 1 to 43. 45. A method of reducing WIZ expression in a cell comprising contacting the cell with a compound or pharmaceutical composition as described in any one of Examples 1 to 43. 46. A method of reducing ZBTB7A expression in a cell comprising contacting the cell with a compound or pharmaceutical composition as described in any one of Examples 1 to 43. 47. A method of inducing HbF expression in a cell and / or reducing ZBTB7A expression in a cell and / or reducing WIZ expression in a cell comprising contacting the cell with a compound or pharmaceutical composition as described in any one of Examples 1 to 43. 48. A method of treating a hemoglobinopathy comprising administering to an individual in need thereof a compound or pharmaceutical composition as described in any one of Examples 1 to 43. 49. The method of Example 48, wherein the hemoglobinopathy is anemia. 50. The method of Example 48, wherein the hemoglobinopathy is sickle cell disease. 51. The method of Example 48, wherein the hemoglobinopathy is thalassemia. 52. The method of Example 48, wherein the hemoglobinopathy is α-thalassemia. 53. The method of Example 48, wherein the hemoglobinopathy is β-thalassemia. 54. Use of a compound or pharmaceutical composition as described in any one of Examples 1 to 43 for treating a hemoglobinopathy. 55. The use of Example 54, wherein the hemoglobinopathy is anemia. 56. The use of Example 54, wherein the hemoglobinopathy is sickle cell disease. 57. The use of Example 54, wherein the hemoglobinopathy is thalassemia. 58. The use of Example 54, wherein the hemoglobinopathy is α-thalassemia. 59. The use of Example 54, wherein the hemoglobinopathy is β-thalassemia. Example The following examples are presented by way of illustration and not limitation. Compounds are named using the automatic naming tool provided by Chemdraw Ultra 20.1 (Cambridgesoft), which generates systematic names for chemical structures with the support of the Cahn-Ingold-Prelog rules for stereochemistry. Those skilled in the art can modify the procedures described in the illustrative examples to obtain the desired products. This document provides the compounds of formula (I), formula (II) and formula (III) described in the following table: Table 1 The compounds disclosed herein can be prepared using conventional organic synthesis and commercially available starting materials. Certain compounds of formula (I), formula (I'), formula (II), formula (II') and formula (III) are prepared as described in the examples below: Examples 1 : 2-(2,6- bis(oxo)piperidine -3- yl )-4-((1- methyl -6- phenoxy -1H- indazole -5- yl ) amino ) isoindoline -1,3- dione 6- bromo -1- methyl -5- nitro -1H- indazole. To a solution of 4-bromo-2-fluoro-5-nitrobenzaldehyde (0.500 g, 2.02 mmol) in propan-2-ol (2 mL) / water (1 mL) was added potassium carbonate (0.420 g, 3.04 mmol). The mixture was stirred at 41 °C for 1 hour and methylhydrazine (0.350 g, 3.04 mmol) (40% purity) was added dropwise. The resulting mixture was heated to 77 °C and stirred for 6 hours. The mixture was cooled to 20 °C and water (8 mL) was added. The mixture was stirred for 1 hour and filtered. The separated solid was washed with water (2 mL) and filtered. The separated solid was mixed with water (20 mL) and lyophilized to give 6-bromo-1-methyl-5-nitro-1H-indazole (0.470 g, 1.84 mmol, 91.045% yield). 1 H NMR (400 MHz, DMSO- d 6 ) δ 8.61 (s, 1H), 8.32 (d, J= 1.2 Hz, 2H), 4.11 (s, 3H). 1- methyl -5- nitro -6- phenoxy -1H- indazole. To a solution of 6-bromo-1-methyl-5-nitro-1H-indazole (0.470 g, 1.84 mmol) in N,N-dimethylformamide (5 mL) was added phenol (0.180 g, 1.91 mmol) and cesium carbonate (1.492 g, 4.59 mmol). The resulting mixture was stirred at 100 °C for 36 hours. The mixture was diluted with water (30 mL) and extracted with ethyl acetate (30 mL × 3). The combined organic layers were washed with brine (20 mL × 3), dried over sodium sulfate and filtered. The filtrate was concentrated under reduced pressure. The resulting crude residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate) to give 1-methyl-5-nitro-6-phenoxy-1H-indazole (0.330 g, 1.22 mmol, 66% yield). 1 H NMR (400 MHz, DMSO- d 6) δ 8.59 (s, 1H), 8.33 (s, 1H), 7.55 (s, 1H), 7.42 - 7.38 (m, 2H), 7.18 - 7.14 (m, 1H), 7.04 (dd, J = 0.8 Hz, 7.6 Hz, 2H), 4.02 (s, 3H); MS (ESI) m / z: 270.0 [M+1] + 。 1- methyl -6- phenoxy -1H- indazole -5- amine. To a solution of 1-methyl-5-nitro-6-phenoxy-1H-indazole (0.260 g, 0.97 mmol) in methanol (50 mL) was added anhydrous Pd / C (0.070 g, 0.66 mmol). The resulting mixture was stirred at 20 °C under 15 psi of hydrogen for 3 hours. The mixture was diluted with methanol (50 mL) and filtered. The filtrate was concentrated under reduced pressure with a water pump. The residue was purified by silica gel column chromatography (ethyl acetate / petroleum ether) to give 1-methyl-6-phenoxy-1H-indazol-5-amine (0.200 g, 0.84 mmol, 86% yield). 1 H NMR (400 MHz, DMSO- d 6 ) δ 7.75 (d, J = 0.8 Hz, 1H), 7.37 - 7.35 (m, 2H), 7.11 (d, J = 7.2 Hz, 1H), 7.07 (s, 1H), 7.00 (d, J = 0.8 Hz, 1H), 6.98 (d, J = 7.6 Hz, 2H), 4.69 (s, 2H), 3.85 (s, 3H); MS (ESI) m / z: 240.1 [M+1] + 。 2-(2,6- bis(oxypiperidine) -3- group )-4-((1- methyl -6- phenoxy -1H- indazole -5- group ) amino ) isoindoline -1,3- dione. To a solution of 1-methyl-6-phenoxy-1H-indazole-5-amine (0.120 g, 0.50 mmol) in 1,4-dioxane (5 mL) was added 4-bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (0.205 g, 0.61 mmol), XPhos-Pd-G2 (0.040 g, 0.05 mmol), and potassium carbonate (0.208 g, 1.51 mmol). The resulting mixture was stirred under nitrogen at 110 °C for 12 hours. The mixture was diluted with dichloromethane and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by preparative TLC (petroleum ether:ethyl acetate) to give the crude product (0.100 g). The crude material was dissolved in N,N-dimethylformamide (2 mL) and filtered. The mixture was purified by preparative HPLC (ACN / water) to give 2-(2,6-dioxopiperidin-3-yl)-4-((1-methyl-6-phenoxy-1H-indazol-5-yl)amino)isoindoline-1,3-dione (44.6 mg, 0.090 mmol, 17% yield). 11H NMR (400 MHz, DMSO-d6) δ 11.11 (s, 1H), 8.19 (s, 1H), 8.05 (s, 1H), 7.94 (s, 1H), 7.60 (dd, J = 7.2 Hz, 8.4 Hz, 1H), 7.35 - 7.31 (m, 3H), 7.29 (d, J = 8.4 Hz, 1H), 7.20 (d, J = 6.8 Hz, 1H), 7.12 - 7.08 (m, 1H), 6.98 - 6.96 (m, 2H), 5.08 (dd, J = 5.2 Hz, 12.8 Hz, 1H), 3.97 (s, 3H), 2.88 - 2.85 (m, 1H), 2.62 - 2.57 (m, 1H), 2.47 - 2.46 (m, 1H), 2.05 - 2.02 (m, 1H); MS (ESI) m / z: 496.2 [M+1] + 。 Example 2 : 2-(2,6- bis(oxo)piperidin-3-yl -3- -yl )-4-((6-(4- fluorophenoxy )-1- methyl -1H- indazole-5- -yl ) amine ) isoindoline-1,3- dione 6-(4- fluorophenoxy )-1- methyl -1H- indazole-5- -yl nitro -1H- indazole. To a solution of 4-fluorophenol (0.219 g, 1.95 mmol) in N,N-dimethylformamide (10 mL) was added sodium hydride (0.047 g, 1.95 mmol). The mixture was stirred at 25 °C for 0.5 h. 6-Bromo-1-methyl-5-nitro-1H-indazole (0.250 g, 0.98 mmol), 2-(dimethylamino)acetic acid (0.010 g, 0.10 mmol), and copper(I) iodide (0.0371 g, 0.20 mmol) were added, and the mixture was purged with nitrogen for 2 min and stirred in a sealed tube at 120 °C for 12 h. The mixture was filtered and concentrated. The residue was purified by preparative TLC (petroleum ether:ethyl acetate) to give 6-(4-fluorophenoxy)-1-methyl-5-nitro-1 H-indazole (0.150 g, 0.52 mmol, 53% yield). MS (ESI) m / z: 288.3 [M+1] + 6-(4- fluorophenoxy )-1- methyl -1 H- indazole -5- amine. To a solution of 6-(4-fluorophenoxy)-1-methyl-5-nitro-1 H-indazole (0.150 g, 0.52 mmol) in acetic acid (1 mL) and water (1 mL) was added iron (0.117 g, 2.09 mmol). The mixture was stirred at 40 °C for 12 h. The mixture was filtered and concentrated. The residue was purified by silica gel preparative TLC (petroleum ether:ethyl acetate) to give 6-(4-fluorophenoxy)-1-methyl-1 H-indazole-5-amine (0.080 g, 0.31 mmol, 59% yield). 1 H NMR (400 MHz, CDCl 3 ) δ 7.77 (s, 1H), 7.06 (m, 7.08 - 7.05, 5H), 6.70 (s, 1H), 3.90 (s, 3H); MS (ESI) m / z: 258.1 [M+1] + 。 2-(2,6- bis(oxo)piperidine -3- yl )-4-((6-(4- fluorophenoxy )-1- methyl -1H- indazole -5- yl ) amino ) isoindoline -1,3- dione. To a solution of 4-bromo-2-(2,6-bis(oxo)piperidin-3-yl)isoindoline-1,3-dione (0.060 g, 0.18 mmol) and 6-(4-fluorophenoxy)-1-methyl-1 H-indazol-5-amine (0.046 g, 0.18 mmol) in 1,4-dioxane (1 mL) was added potassium carbonate (0.074 g, 0.53 mmol) and chloro(2-dicyclohexylphosphino-2,4,6-triisopropyl-1,1-biphenyl)[2-(2-amino-1,1-biphenyl)]palladium(II) (0.014 g, 0.02 mmol). The mixture was stirred under nitrogen at 110 °C for 12 hours. The mixture was filtered and concentrated. The residue was purified by preparative HPLC. The organic solvent was removed and the preparative liquid was lyophilized to give 2-(2,6-bis(oxo)piperidin-3-yl)-4-((6-(4-fluorophenoxy)-1-methyl-1 H-indazol-5-yl)amino)isoindoline-1,3-dione (0.050 g, 0.10 mmol, 54% yield). The crude residue was dissolved in dichloromethane (5 mL) and purified by preparative TLC (petroleum ether:ethyl acetate). The mixture was filtered and concentrated. The solid was dissolved in acetonitrile (10 mL) and water (15 mL). The preparative liquid was lyophilized to give 2-(2,6-bis(oxo)piperidin-3-yl)-4-((6-(4-fluorophenoxy)-1-methyl-1 H-indazol-5-yl)amino)isoindoline-1,3-dione (28 mg, 0.054 mmol, 55% yield) and 2-(2,6-bis(oxo)piperidin-3-yl)-4-((6-(4-fluorophenoxy)-1-methyl-1 (H-indazol-5-yl)amino)isoindoline-1,3-dione (2.4 mg, 0.004 mmol, 4% yield). 1 H NMR (400 MHz, DMSO- d 6 ) δ 11.11 (s, 1H), 8.20 (s, 1H), 8.04 (d, J= 0.8 Hz, 1H), 7.91 (s, 1H), 7.58 (dd, J= 7.6 Hz, 8.8 Hz, 1H), 7.27 - 7.23 (m, 2H), 7.20 - 7.14 (m, 3H), 7.03 - 7.00 (m, 2H), 5.11 - 5.06 (m, 1H), 3.96 (s, 3H), 2.93 - 2.84 (m, 1H), 2.61 - 2.54 (m, 2H), 2.07 - 1.99 (m, 1H); MS (ESI) m / z: 514.2 [M+1] + 。 Example 3 : 2-(2,6- bis(oxypiperidine) -3- yl )-4-((6- methoxy -4- phenylpyridine -3- yl ) amino ) isoindoline -1,3- dione 2- chloro -5- nitro -4- phenyl - pyridine. To a degassed solution of 2,4-dichloro-5-nitro-pyridine (0.40 g, 2.07 mmol) in 1,4-dioxane (10 mL) and water (2 mL) was added phenylboronic acid (0.252 g, 2.07 mmol), potassium carbonate (0.858 g, 6.22 mmol) and dichloro(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) (0.169 g, 0.2100 mmol). The resulting mixture was heated at 60 °C for 18 h under nitrogen. The mixture was cooled and partitioned between water (50 mL) and ethyl acetate (30 mL × 3). The combined organic layers were dried over sodium sulfate and concentrated, and the residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate) to give 2-chloro-5-nitro-4-phenyl-pyridine (350 mg, 1.49 mmol, 71% yield). 1 H NMR (400 MHz, CDCl 3 ) δ 8.92 (s, 1H), 7.53 - 7.51 (m, 3H), 7.47 (s, 1H), 7.37 - 7.35 (m, 2H); MS (ESI) m / z: 235.4 [M+1] + 。 2- methoxy -5- nitro -4- phenylpyridine. To a solution of 2-chloro-5-nitro-4-phenyl-pyridine (0.20 g, 0.8500 mmol) in methanol (10 mL) was added sodium methoxide (0.13 g, 2.56 mmol). The solution was stirred at 25 °C for 12 h. The reaction liquid was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate from 8:1 to 4:1) to afford 2-methoxy-5-nitro-4-phenyl-pyridine (150 mg, 0.651 mmol, 76% yield). 1 H NMR (400 MHz, CDCl 3) δ 8.85 (s, 1H), 7.80 - 7.45 (m, 3H), 7.32 - 7.31 (m, 2H), 6.74 (s, 1H), 4.06 (s, 3H); MS (ESI) m / z: 231.0 [M+1] + 。 6- Methoxy -4- Phenylpyridine -3- Amine. To a solution of 2-methoxy-5-nitro-4-phenyl-pyridine (0.150 g, 0.6500 mmol) in methanol (10 mL) was added wet Pd / activated carbonate (0.03 g). The suspension was degassed under nitrogen. The solution was stirred at 25 °C under hydrogen (15 psi) for 12 hours. The suspension was filtered and the filtrate was concentrated to give 6-methoxy-4-phenyl-pyridin-3-amine (130 mg, 0.64 mmol, 99% yield). MS (ESI) m / z: 269.5 [M+1] + 2-(2,6- Dioxopiperidine -3- yl )-4-((6- Methoxy -4- Phenylpyridine -3- yl ) Amino ) Isoindoline -1,3- Dione. Under nitrogen, to a solution of 6-methoxy-4-phenyl-pyridin-3-amine (0.10 g, 0.50 mmol) and 4-bromo-2-(2,6-dioxo-3-piperidinyl)isoindoline-1,3-dione (0.168 g, 0.500 mmol) in 1,4-dioxane (5 mL) was added chloro(2-dicyclohexylphosphino-2,4,6-triisopropyl-1,1-biphenyl)[2-(2-amino-1,1-biphenyl)]palladium(II) (0.019 g, 0.020 mmol) and potassium carbonate (0.206 g, 1.500 mmol). The suspension was degassed under vacuum and purged with nitrogen several times. The reaction mixture was stirred at 110 °C for 12 h. The suspension was filtered and the filtrate was concentrated, and the residue was purified by preparative HPLC. Subsequently, the resulting solution was lyophilized, and the crude product was purified by preparative TLC to give 2-(2,6-dioxo-3-piperidinyl)-4-[(6-methoxy-4-phenyl-3-pyridinyl)amino]isoindoline-1,3-dione (150 mg, 0.330 mmol, 66% yield). 1H NMR (400 MHz, DMSO-d6) δ 11.10 (s, 1 H), 8.23 (s, 1 H), 8.19 (s, 1 H), 7.53 -7.52 (m, 1 H), 7.51 - 7.34(m, 4 H), 7.04 (d, J = 6.8 Hz, 1 H), 6.91 (s, 1 H), 6.67 (d, J = 6.8 Hz, 1 H), 5.08 - 5.04 (m, 1 H), 3.93 (s, 3 H), 2.91 - 2.90 (m, 1 H), 2.60 - 2.58 (m, 2 H), 2.08 - 2.04 (m, 1 H); MS (ESI) m / z: 457.2 [M+1] + 。 Example 4 : 2-(2,6- Dioxopiperidine -3- yl )-4-((6- Methyl -4- Phenoxypyridine -3- yl ) Amino ) Isoindoline -1,3- Dione 5- Bromo -2- Methyl -4- Phenoxy - Pyridine. To a solution of phenol (0.040 g, 0.43 mmol) in N-methylpyrrolidone (1.5 mL) was added cesium carbonate (0.345 g, 1.06 mmol) and 5-bromo-4-chloro-2-methyl-pyridine (0.105 g, 0.51 mmol). The mixture was stirred at 90 °C for 4 hours. The reaction mixture was diluted with water (10 mL) and extracted with ethyl acetate (12 mL × 3). The combined organic layers were washed with brine (10 mL × 2), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo, and the resulting residue was purified by silica gel preparative TLC (petroleum ether:ethyl acetate) to give 5-bromo-2-methyl-4-phenoxypyridine (0.080 g, 0.30 mmol, 71% yield). 1 H NMR (400 MHz, CDCl 3 ) δ 8.62 (s, 1H), 7.52 - 7.48 (m, 2H), 7.35 (t, J = 7.2 Hz, 1H), 7.14 (d, J = 7.6 Hz, 2H), 6.53 (s, 1H), 2.53 (s, 3H); MS (ESI) m / z: 264.0 [M+1] + . 2-(2,6- Dioxido -3- Piperidinyl )-4-[(6- Methyl -4- Phenoxy -3- Pyridinyl ) Amino ] Isoindoline -1,3- Dione. To a solution of 5-bromo-2-methyl-4-phenoxypyridine (0.060 g, 0.23 mmol) and 4-amino-2-(2,6-dioxo-3-piperidinyl)isoindoline-1,3-dione (0.062 g, 0.23 mmol) in 1,4-dioxane (1 mL) was added chloro(2-dicyclohexylphosphino-2,4,6-triisopropyl-1,1-biphenyl)[2-(2-amino-1,1-biphenyl)]palladium(II) (0.018 g, 0.02 mmol) and potassium carbonate (0.031 g, 0.23 mmol). The mixture was stirred under nitrogen at 110 °C for 12 hours. The mixture was filtered and concentrated. The residue was purified by silica gel preparative TLC (petroleum ether:ethyl acetate) to give 2-(2,6-dioxo-3-piperidinyl)-4-[(6-methyl-4-phenoxy-3-pyridinyl)amino]isoindoline-1,3-dione (29 mg, 0.06 mmol, 27% yield). 1 H NMR (400 MHz, DMSO- d 6 ) δ 11.13 (s, 1H), 8.78 (s, 1H), 8.73 (s, 1H), 7.71 (t, J= 7.8 Hz, 1H), 7.56 - 7.52 (m, 2H), 7.40 - 7.36 (m, 3H), 7.27 (d, J= 8.4 Hz, 2H), 6.98 (s, 1H), 5.12 (dd, J= 5.2, 12.8 Hz, 1H), 2.94 - 2.85 (m, 1H), 2.62 - 2.56 (m, 2H), 2.55 (s, 3H), 2.07 - 2.03 (m, 1H); MS (ESI) m / z: 456.9 [M+1] + 。 Example 5 : 4-((6-(2-( Dimethylamino ) Ethoxy )-4- Phenoxypyridine -3- yl ) Amino )-2-(2,6- Dioxopiperidine -3- yl ) Isoindoline -1,3- Dione 2-((4- Chloro -5- Nitropyridine -2- yl ) Oxy )-N,N- Dimethylethylamine. To a solution of 4-chloro-5-nitro-pyridin-2-ol (1.50 g, 8.59 mmol) in tetrahydrofuran (30 mL) was added 2-chloro-N,N-dimethylethylamine hydrochloride (1.857 g, 12.89 mmol) and silver carbonate (7.11 g, 25.78 mmol). The mixture was stirred at 15 °C for 12 h. The mixture was concentrated under reduced pressure. The residue was diluted with water (20 mL) and dichloromethane (50 mL) and the mixture was filtered. The organic layer of the filtrate was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give 2-((4-chloro-5-nitropyridin-2-yl)oxy)-N,N-dimethylethylamine (0.10 g, 0.41 mmol, 5% yield). 1 H NMR (400 MHz, CDCl 3 ) δ 8.67 (s, 1H), 6.67 (s, 1H), 4.09 - 4.02 (m, 2H), 2.69 - 2.60 (m, 2H), 2.29 (s, 6H); MS (ESI) m / z 246.1 [M+1] + . N,N- Dimethyl -2-((5- nitro -4- phenoxypyridine -2- yl ) oxy ) ethylamine. At 0 °C, a solution of sodium phenoxide (0.064 g, 0.55 mmol) in N,N-dimethylformamide (1 mL) was added dropwise to a solution of 2-((4-chloro-5-nitropyridin-2-yl)oxy)-N,N-dimethylethylamine (0.090 g, 0.37 mmol) in N,N-dimethylformamide (1 mL). The mixture was stirred at 15 °C for 2 hours. The mixture was filtered and the filtrate was purified by preparative HPLC. The mixture was evaporated to remove the organic phase and the aqueous phase was lyophilized to give N,N-dimethyl-2-[(5-nitro-4-phenoxy-2-pyridinyl)oxy]ethylamine (0.013 g, 0.04 mmol, 12% yield). 1 H NMR (400 MHz, CDCl 3 ) δ 8.87 (s, 1H), 7.50 - 7.45 (m, 2H), 7.36 - 7.31 (m, 1H), 7.17 - 7.13 (m, 2H), 6.11 (s, 1H), 4.72 - 4.34 (m, 2H), 3.10 - 2.59 (m, 2H), 2.57 - 2.18 (m, 6H); MS (ESI) m / z 304.1[M+1] + . 6-(2-( dimethylamino ) ethoxy )-4- phenoxypyridine -3- amine. Under nitrogen, palladium / carbon catalyst (0.010 g, 0.05 mmol) was added to a solution of N,N-dimethyl-2-[(5-nitro-4-phenoxy-2-pyridyl)oxy]ethylamine (0.013 g, 0.04 mmol) in methanol (5 mL). The suspension was degassed under vacuum and purged with nitrogen several times. The mixture was stirred at 15 °C under hydrogen (15 Psi) for 12 hours. The mixture was filtered and the filtrate was concentrated under reduced pressure. The crude product was used directly in the next step without purification. 6-[2-(Dimethylamino)ethoxy]-4-phenoxypyridin-3-amine (0.01 g, 0.04 mmol, 85% yield). MS (ESI) m / z 274.1 [M+1] + 4-((6-(2-( Dimethylamino ) Ethoxy )-4- Phenoxypyridine -3- yl ) Amino )-2-(2,6- Dioxopiperidine -3- yl ) Isoindoline -1,3- Dione. To a solution of 6-[2-(dimethylamino)ethoxy]-4-phenoxypyridin-3-amine (0.010 g, 0.04 mmol) in 1,4-dioxane (3 mL) was added 4-bromo-2-(2,6-dioxo-3-piperidyl)isoindoline-1,3-dione (15 mg, 0.04 mmol), potassium carbonate (15 mg, 0.11 mmol) and chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)(2'-amino-1,1'-biphenyl-2-yl)palladium(II) (3 mg). The suspension was degassed under vacuum and purged with nitrogen several times. The mixture was stirred at 110 °C for 12 hours. The mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by preparative HPLC to give 4-((6-(2-(dimethylamino)ethoxy)-4-phenoxypyridin-3-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (3.41 mg, 0.006 mmol, 17% yield). 1 H NMR (400 MHz, DMSO-d 6 ) δ 11.12 (s, 1H), 10.08 - 9.87 (m, 1H), 8.23 ​​(s, 2H), 7.61 (dd, J= 7.4, 8.4 Hz, 1H), 7.52 - 7.44 (m, 2H), 7.33 - 7.27 (m, 1H), 7.24 - 7.19 (m, 1H), 7.19 - 7.13 (m, 2H), 7.05 (d, J= 8.4 Hz, 1H), 6.04 (s, 1H), 5.10 (dd, J= 5.4, 12.8 Hz, 1H), 4.61 - 4.50 (m, 2H), 3.48 - 3.44 (m, 2H), 2.95 - 2.86 (m, 1H), 2.79 (s, 6H), 2.64 - 2.57 (m, 2H), 2.09 - 2.01 (m, 1H); MS (ESI) m / z 530.3 [M+1] + . Examples 6 : 2-(2,6- Dihydroxypiperidine -3- base )-4-((6-(3- Fluorophenoxy )-1-( Tetrahydrogen -2H- Pyran -4- base )-1H- Indazole -5- base ) Amine ) Isoindoline -1,3- Diketone 6- Fluorine -5- Nitro -1H- Indazole. At 0 °C, potassium nitrate (7.4 g, 7.35 mmol) was added to a solution of 6-fluoro-1H-indazole (10.000 g, 73.50 mmol) in concentrated sulfuric acid (220 mL). The resulting mixture was stirred at 25 °C for 12 hours. The mixture was added dropwise to ice water (1000 mL) and extracted with ethyl acetate (200 mL × 2). The combined organic phases were washed with brine (200 mL × 2), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Purification by silica gel column chromatography (40 - 50% ethyl acetate / petroleum ether) gave 6-fluoro-5-nitro-1H-indazole (3.0 g, 16.56 mmol, 22% yield). NMR (400 MHz, DMSO- d 6 ) δ 8.79 (d, J = 7.2 Hz, 1H), 8.38 (s, 1H), 7.68 (d, J = 12.0 Hz, 1H). 6- Fluorine -5- Nitro -1-((2-( Trimethylsilyl ) Ethoxy ) Methyl )-1H- Indazole. To a solution of 6-fluoro-5-nitro-1H-indazole (3.00 g, 16.56 mmol) in N,N-dimethylformamide (30 mL) at 0 °C was added sodium hydride (6.34 g, 26.50 mmol). The mixture was stirred for 0.5 h and then (2-(chloromethoxy)ethyl)trimethylsilane (4.3 mL, 24.29 mmol) was added to the mixture. The mixture was extracted with ethyl acetate (200 mL × 2). The combined organic phases were washed with brine (100 mL × 2), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The resulting crude material was purified by silica gel column chromatography (20 - 25% ethyl acetate / petroleum ether) to give 6-fluoro-5-nitro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole (1.00 g, 3.21 mmol, 14% yield). 1 H NMR (400 MHz, DMSO- d 6 ) δ 8.81 (d, J= 7.2 Hz, 1H), 8.45 (s, 1H), 8.04 (d, J= 12.0 Hz, 1H), 5.80 (s, 2H), 3.55 (t, J= 8.0 Hz, 2H), 3.32 (s, 3H), 0.05 (s, 2H), 0.09 (s, 1H), 0.10 (s, 6H). 6-(3- fluorophenoxy )-5- nitro -1-((2-( trimethylsilyl ) ethoxy ) methyl )-1H- indazole. To a solution of 6-fluoro-5-nitro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole (1.00 g, 3.20 mmol) in N,N-dimethylformamide (10 mL) was added 3-fluorophenol (0.432 g, 0.39 mmol) and potassium carbonate (0.668 g, 0.48 mmol). The resulting mixture was stirred at 110 °C for 12 h. The mixture was extracted with ethyl acetate (100 mL × 2). The combined organic phases were washed with brine (50 mL × 2), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The resulting crude material was purified by silica gel column chromatography (20-25% ethyl acetate / petroleum ether) to give 6-(3-fluorophenoxy)-5-nitro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole (0.70 g, 1.73 mmol, 54% yield). 1 HNMR (400 MHz, DMSO- d 6 ) δ 9.85 (s, 1H), 8.75 (s, 1H), 8.43 (s, 1H), 7.73 (s, 1H), 7.43 (d, J= 1.6, 6.8 Hz, 1H), 7.17 (s, 1H), 7.01 - 6.95 (m, 1H), 6.93 (m, 1H), 6.88 (t, J= 2.0 Hz, 1H), 6.55 (m, 2H), 5.76 (s, 2H), 3.51 (t, J= 8.0, 2H ), 0.14 (s, 9H). 6-(3- fluorophenoxy )-5- nitro -1H- indazole. To a solution of 6-(3-fluorophenoxy)-5-nitro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole (0.700 g, 1.70 mmol) in dichloromethane (2 mL) was added trifluoroacetic acid (0.5 mL, 0.10 mmol), and the mixture was stirred at 25 °C for 12 hours. The mixture was extracted with ethyl acetate (100 mL × 2). The combined organic phases were washed with brine (100 mL × 2), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo, and purified by silica gel column chromatography (10 - 20% ethyl acetate / petroleum ether) to give 6-(3-fluorophenoxy)-5-nitro-1H-indazole (0.50 g, 1.83 mmol, 61% yield). 1 H NMR (400 MHz, DMSO- d 6 ) δ 8.72 (s, 1H), 7.68 (s, 1H), 7.33 (s, 1H), 7.02 - 6.99 (m, 2H), 6.98 - 6.88 (m, 2H). 6-(3- fluorophenoxy )-5- nitro -1-( tetrahydro -2H- pyran -4- yl )-1H- indazole. To a solution of 6-(3-fluorophenoxy)-5-nitro-1H-indazole (0.10 g, 0.37 mmol) in dimethylformamide (2 mL) was added 4-iodotetrahydro-2H-pyran (0.093 g, 0.44 mmol) and potassium carbonate (0.151 g, 1.10 mmol). The mixture was stirred at 110 °C for 12 hours. The mixture was filtered. The filtrate was purified by preparative HPLC to give 6-(3-fluorophenoxy)-5-nitro-1-(tetrahydro-2H-pyran-4-yl)-1H-indazole (0.02 g, 0.042 mmol, 11% yield). MS (ESI) m / z: 538.2[M+1]+ 6-(3- fluorophenoxy )-1-( tetrahydro -2H- Pyran -4- yl )-1H- Indazole -5- amine. To a solution of 6-(3-fluorophenoxy)-5-nitro-1-(tetrahydro-2H-pyran-4-yl)-1H-indazole (0.015 g, 0.04 mmol) in ethanol (1.5 mL) and water (0.50 mL) was added iron powder (0.007 g, 0.13 mmol) and ammonium chloride (0.022 g, 0.42 mmol). The mixture was stirred at 80 °C for 2 hours. The reaction mixture was filtered and the filtrate was concentrated to give 6-(3-fluorophenoxy)-1-(tetrahydro-2H-pyran-4-yl)-1H-indazol-5-amine (0.008 g, 0.024 mmol, 58% yield). MS (ESI) m / z: 328.1 [M+1] + 2-(2,6- bis(oxypiperidine) -3- yl )-4-((6-(3- fluorophenoxy )-1-( tetrahydro -2H- pyran -4- yl )-1H- indazole -5- yl ) amino ) isoindoline -1,3- dione. To a solution of 6-(3-fluorophenoxy)-1-(tetrahydro-2H-pyran-4-yl)-1H-indazol-5-amine (0.008 g, 0.03 mmol) in 1,4-dioxane (2 mL) was added 4-bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (0.018 g, 0.05 mmol), chloro(2-dicyclohexylphosphino-2,4,6-triisopropyl-1,1-biphenyl)[2-(2-amino-1,1-biphenyl)]palladium(II) (0.036 g, 0.01 mmol), and potassium carbonate (0.006 g, 0.05 mmol). The mixture was stirred under nitrogen at 110 °C for 12 hours. The solution was filtered and concentrated, and purified by preparative HPLC to give 2-(2,6-dioxopiperidin-3-yl)-4-((6-(3-fluorophenoxy)-1-(tetrahydro-2H-pyran-4-yl)-1H-indazol-5-yl)amino)isoindoline-1,3-dione (7.82 mg, 0.013 mmol, 28% yield). 1 H NMR (400 MHz, DMSO- d 6 ) δ 11.12-11.04 (m, 1H), 8.11 (d, J= 7.2 Hz, 2H), 7.95 (s, 1H), 7.67 (s, 1H), 7.56-7.32 (m, 1H), 7.30 (m, 1H), 7.24-7.22 (m, 2H), 7.19 - 7.17 (m, 1H), 6.78-6.74 (m, 2H), 5.07 (dd, J= 4.8, 12.4, 1H), 4.86 (s, 1H), 4.00 - 3.96 (m, 2H), 3.53 (t, J= 12.8 Hz, 2H), 2.61 (m, 1H), 2.60 (m, 2H), 2.12 - 2.04 (m, 2H), 1.90 - 1.86 (m, 2H), 1.24 (s, 1H); MS (ESI) m / z: 584.2 [M+1] + 。 Example 7 : 2-(2,6- dioxopiperidine -3- base )-4-((1- methyl -6-(2- methylpyridine -4- group )-1H- indazole -5- group ) amino ) isoindoline -1,3- dione 1- methyl -6-(2- methylpyridine -4- group )-5- nitro -1H- indazole. To a solution of 6-bromo-1-methyl-5-nitro-1H-indazole (0.300 g, 1.17 mmol) and 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.282 g, 1.29 mmol) in 1,4-dioxane (3 mL) was added cesium carbonate (1.14 g, 3.51 mmol) and dichloro(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) (0.096 g, 0.120 mmol). The resulting mixture was stirred under nitrogen at 110 °C for 12 hours. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by preparative HPLC to give 1-methyl-6-(2-methylpyridin-4-yl)-5-nitro-1H-indazole (0.250 mg, 0.931 mmol, 79% yield). 1 H NMR (400 MHz, CDCl3) δ 8.80 (d, J = 5.6 Hz, 1H), 8.67 (s, 1H), 8.23 (s, 1H), 7.52 (d, J = 5.6 Hz, 1H), 7.46 (s, 1H), 7.19 (s, 1H), 4.12 (s, 3H), 2.83 (s, 3H); MS (ESI) m / z: 268.8[M-100] + 。 1- methyl -6-(2- methylpyridine -4- yl )-1H- indazole -5- amine. To a solution of 1-methyl-6-(2-methylpyridin-4-yl)-5-nitro-1H-indazole (0.250 g, 0.930 mmol) in ethanol (3 mL) and water (1 mL) was added ammonium chloride (0.503 g, 9.32 mmol) and iron powder (0.520 g, 9.32 mmol). The resulting mixture was stirred at 70 °C for 2 h. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by preparative TLC (petroleum ether: ethyl acetate) to give 1-methyl-6-(2-methylpyridin-4-yl)-1H-indazol-5-amine (0.145 g, 0.638 mmol, 96% yield). MS (ESI) m / z: 239.1[M+1] + 。 2-(2,6- bis(oxo)piperidine -3- yl )-4-((1- methyl -6-(2- methylpyridine -4- yl )-1H- indazole -5- yl ) amino ) isoindoline -1,3- dione. To a solution of 1-methyl-6-(2-methylpyridin-4-yl)-1H-indazol-5-amine (0.070 g, 0.290 mmol) and 4-bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (0.099 g, 0.290 mmol) in 1,4-dioxane (2 mL) was added chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) (0.024 g, 0.030 mmol) and potassium carbonate (0.122 g, 0.880 mmol). The resulting mixture was stirred at 110 °C under nitrogen for 12 h. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure by a water pump. The residue was purified by preparative HPLC to give 2-(2,6-dioxopiperidin-3-yl)-4-((1-methyl-6-(2-methylpyridin-4-yl)-1H-indazol-5-yl)amino)isoindoline-1,3-dione (93 mg, 0.188 mmol, 64% yield). 1 H NMR (400 MHz, DMSO-d6) δ 11.14 (s, 1H), 8.73 (d, J = 6.4 Hz, 1H), 8.51 (s, 1H), 8.19 (s, 1H), 8.12 (s, 1H), 8.05 (s, 1H), 7.99 (d, J = 5.2 Hz, 1H), 7.94 (s, 1H), 7.40 (dd, J = 7.2, 8.4 Hz, 1H), 7.09 (d, J = 7.2 Hz, 1H), 6.66 (d, J = 8.4 Hz, 1H), 5.10 (dd, J = 5.6, 12.8 Hz, 1H), 4.16 (s, 3H), 2.91 - 2.88 (m, 1H), 2.67 (s, 3H), 2.58 (d, J = 12.8 Hz, 2H), 2.08 - 2.05 (m, 1H); MS (ESI) m / z: 495.1 [M+1] + 。 Example 8 : 4-((5-(2- chlorophenoxy )-1-( tetrahydro -2H- Pyran -4- yl )-1H- Indazole -4- yl ) Amino )-2-(2,6- Bis(oxypiperidine) -3- yl ) Isoindoline -1,3- Dione 5- Fluoro -4- Nitro -1H- Indazole. A solution of 5-fluoro-1H-indazole (10 g, 73.46 mmol) in concentrated sulfuric acid (200 mL, 73.46 mmol) was cooled to 0 °C. Fuming nitric acid (10.00 mL, 224.29 mmol) was added dropwise, and the reaction mixture was stirred at 0 °C for 1 hour. The reaction mixture was poured onto ice water (1000 mL), and the precipitate was collected by filtration, washed with water (300 mL), and dried under reduced pressure to give the crude product 5-fluoro-4-nitro-1H-indazole (8 g, yield: 60%). 1 H NMR (400 MHz, DMSO- d 6 ) δ 11.29 - 11.20 (m, 1H), 8.33 (d, J = 0.8 Hz, 1H), 7.95 (dd, J = 0.8, 8.8 Hz, 1H), 7.21 (d, J = 8.8 Hz, 1H). 2-[(5- Fluoro -4- Nitro - Indazole -1- yl ) Methoxy ] ethyl - trimethyl - silane. To a solution of 5-fluoro-4-nitro-1H-indazole (8.0 g, 44.1 mmol) in dimethylformamide (80 mL) was added sodium hydride (1.9 g, 48.59 mmol) at 0 °C, and the mixture was stirred for 0.5 h. (2-(Chloromethoxy)ethyl)trimethylsilane (8.8 g, 53.0 mmol) was added. The mixture was stirred at 25 °C for 12 h. The mixture was quenched with water (50 mL) and extracted with ethyl acetate (100 mL × 2). The combined organic layers were washed with lithium chloride solution (30 mL × 2), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by preparative HPLC to give the product 2-[(5-fluoro-4-nitro-indazol-1-yl)methoxy]ethyl-trimethyl-silane (3.0 g, yield: 21%). 1 H NMR (400 MHz, DMSO- d 6 ) δ 8.26 (s, 1H), 8.16 (d, J= 9.2 Hz, 1H), 7.63 (d, J= 9.2 Hz, 1H), 5.46 (s, 2H), 3.55 - 3.49 (m, 2H), 0.82 - 0.79 (m, 2H), -0.12 (s, 9H). 2-[[5-(2- chlorophenoxy )-4- nitro - indazole -1- yl ] methoxy ] ethyl - trimethyl - silane. To a solution of 2-chlorophenol (0.136 g, 1.06 mmol) in dimethylformamide (4 mL) was added cesium carbonate (0.626 g, 1.93 mmol) and 2-[(5-fluoro-4-nitro-indazol-1-yl)methoxy]ethyl-trimethyl-silane (0.300 g, 0.96 mmol). The mixture was stirred at 25 °C for 12 h. The mixture was diluted with 20 mL of water and extracted with ethyl acetate (20 mL × 2). The combined organic layers were washed with lithium chloride solution (10 mL × 2), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give a residue. The residue was purified by preparative TLC (ethyl acetate) to give the product 2-[[5-(2-chlorophenoxy)-4-nitro-indazol-1-yl]methoxy]ethyl-trimethyl-silane (0.370 g, yield: 91%). MS (ESI) m / z: 421.2 [M+1] + 5-(2- chlorophenoxy )-4- nitro -1H- indazole. To a solution of 2-[[5-(2-chlorophenoxy)-4-nitro-indazol-1-yl]methoxy]ethyl-trimethyl-silane (0.370 g, 0.88 mmol) in dichloromethane (2 mL) was added trifluoroacetic acid (2 mL, 26.12 mmol). The mixture was stirred at 25 °C for 3 h. The mixture was evaporated and the resulting residue was purified by preparative TLC (ethyl acetate) to give 5-(2-chlorophenoxy)-4-nitro-1H-indazole (0.110 g, yield: 43%). 1 H NMR (400 MHz, CDCl 3 ) δ 8.57 (s, 1H), 7.81 - 7.78 (m, 1H), 7.51 (d, J= 1.2 Hz, 1H), 7.30 - 7.29 (m, 1H), 7.19 - 7.17 (m, 1H), 7.12 - 7.11 (m, 1H), 6.99 - 6.97 (m, 1H); MS (ESI) m / z: 290.2 [M+1] + . 5-(2- chlorophenoxy )-4- nitro -1- tetrahydropyran -4- yl - indazole. To a solution of 5-(2-chlorophenoxy)-4-nitro-1H-indazole (0.050 g, 0.17 mmol) and 4-iodotetrahydropyran (0.044 g, 0.21 mmol) in dimethylformamide (1 mL) was added potassium carbonate (0.048 g, 0.35 mmol). The mixture was stirred at 85 °C for 12 h. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure with a water pump to give a residue. The residue was purified by preparative HPLC to give the product 5-(2-chlorophenoxy)-4-nitro-1-tetrahydropyran-4-yl-indazole (0.010 g, yield: 15%). 1 H NMR (400 MHz, CDCl 3 ) δ 8.45 (s, 1H), 7.67 (d, J= 9.2 Hz, 1H), 7.51 (dd, J= 1.6, 8.0 Hz, 1H), 7.26 - 7.22 (m, 1H), 7.16 - 7.12 (m, 1H), 7.06 (d, J= 8.8 Hz, 1H), 6.93 (dd, J= 1.2, 8.0 Hz, 1H), 4.71 - 4.63 (m, 1H), 4.23 - 4.19 (m, 2H), 3.67 - 3.61 (m, 2H), 2.50 - 2.39 (m, 2H), 2.04 - 2.00 (m, 2H); MS (ESI) m / z: 374.1 [M+1] + . 5-(2- chlorophenoxy )-1- tetrahydropyran -4- yl - indazole -4- Amine. To a solution of 5-(2-chlorophenoxy)-4-nitro-1-tetrahydropyran-4-yl-indazole (0.023 g, 0.06 mmol) in ethanol (1 mL) and water (0.30 mL) was added ammonium chloride (0.033 g, 0.62 mmol) and iron powder (0.017 g, 0.31 mmol). The mixture was stirred at 80 °C for 2 hours. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by preparative TLC (100% ethyl acetate) to give the product 5-(2-chlorophenoxy)-1-tetrahydropyran-4-yl-indazole-4-amine (0.013 g, yield: 61%). 1 H NMR (400 MHz, CDCl3) δ 7.99 (s, 1H), 7.45 (dd, J = 1.6, 8.0 Hz, 1H), 7.13 - 7.08 (m, 1H), 7.04 (d, J = 8.8 Hz, 1H), 6.99 - 6.95 (m, 1H), 6.82 (d, J = 9.2 Hz, 1H), 6.74 (dd, J = 1.2, 8.4 Hz, 1H), 4.62 - 4.54 (m, 1H), 4.20 - 4.16 (m, 2H), 3.65 - 3.59 (m, 2H), 2.46 -2.35(m, 2H), 2.03 - 1.99 (m, 2H); MS (ESI) m / z: 344.1 [M+1] + . 3-[[5-(2- Chlorophenoxy )-1- Tetrahydropyran -4- -yl - Indazole -4- -yl ] Amino ] Benzene -1,2- Dimethyl phthalate. Under nitrogen, potassium carbonate (0.016 g, 0.11 mmol) and chloro(2-dicyclohexylphosphino-2,4,6-triisopropyl-1,1-biphenyl)[2-(2-amino-1,1-biphenyl)]palladium(II) (0.003 g) were added to a solution of 5-(2-chlorophenoxy)-1-tetrahydropyran-4-yl-indazole-4-amine (0.013 g, 0.04 mmol) and dimethyl 3-bromobenzene-1,2-dicarboxylate (0.011 g, 0.04 mmol) in 1,4-dioxane (1 mL). The suspension was degassed under vacuum and purged with nitrogen several times. The reaction mixture was stirred at 90 °C for 12 hours. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by preparative TLC (ethyl acetate) to give the product dimethyl 3-[[5-(2-chlorophenoxy)-1-tetrahydropyran-4-yl-indazole-4-yl]amino]benzene-1,2-dicarboxylate (0.020 g, 98%). MS (ESI) m / z: 536.1 [M+1] + 。 4-[[5-(2- chlorophenoxy )-1- tetrahydropyran -4- yl - indazole -4- yl ] amino ]-2-(2,6- dioxido -3- piperidinyl ) isoindoline -1,3- dione. To a solution of dimethyl 3-[[5-(2-chlorophenoxy)-1-tetrahydropyran-4-yl-indazol-4-yl]amino]benzene-1,2-dicarboxylate (0.020 g, 0.04 mmol) and 3-aminopiperidine-2,6-dione hydrochloride (0.007 g, 0.04 mmol) in pyridine (1 mL) was added lithium iodide (0.01 mL, 0.11 mmol). The suspension was degassed under vacuum and purged with nitrogen several times. The reaction mixture was stirred at 120 °C for 12 h. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by preparative HPLC to give the product 4-[[5-(2-chlorophenoxy)-1-tetrahydropyran-4-yl-indazol-4-yl]amino]-2-(2,6-dioxo-3-piperidyl)isoindoline-1,3-dione (10 mg, 40%). 1 H NMR (400 MHz, DMSO- d 6 ) δ 11.11 (s, 1H), 8.29 (s, 1H), 7.97 (s, 1H), 7.72 (d, J= 9.2 Hz, 1H), 7.57 - 7.53 (m, 1H), 7.44 (dd, J= 1.6, 8.0 Hz, 1H), 7.24 (d, J= 7.2 Hz, 1H), 7.20 - 7.15 (m, 2H), 7.05 - 6.97 (m, 2H), 6.83 (dd, J= 1.2, 8.4 Hz, 1H), 5.10 - 5.06 (m, 1H), 4.99 - 4.91 (m, 1H), 4.04 - 3.97 (m, 2H), 3.61 - 3.55 (m, 2H), 2.93 - 2.83 (m, 1H), 2.62 - 2.54 (m, 2H), 2.18 - 2.12 (m, 2H), 2.04 - 2.00 (m, 1H), 1.96 - 1.92 (m, 2H); MS (ESI) m / z: 600.2 [M+1] + 。 Example 9 : 2-(2,6- dioxopiperidine -3- base )-4-((6-(3- fluoro -4- methoxyphenyl )-1- methyl -1H- indazole -5- group ) amino ) isoindoline -1,3- dione 6- bromo -1- methyl -5- nitro -1H- indazole. Add 4-bromo-2-fluoro-5-nitrobenzaldehyde (15 g, 60.48 mmol), potassium carbonate (12.6 g, 91.3 mmol), isopropanol (120 mL) and water (60 mL) to a 250 mL three-necked flask. Stir the mixture at 41 °C for 1 hour. Then add methylhydrazine (10.5 g, 91.17 mmol) dropwise. Stir the resulting mixture at 77 °C for 6 hours. Cool the mixture to 20 °C and add water (240 mL). Stir the mixture for 1 hour and filter. Wash the separated solid with water (20 mL × 3) and filter. Dry the solid under reduced pressure to obtain 6-bromo-1-methyl-5-nitro-1H-indazole (7.0 g, 27.3 mmol, 45% yield). 1 H NMR (400 MHz, CDCl 3 ) δ 8.30 (s, 1H), 8.06 (s, 1H), 7.69 (s, 1H), 4.04 (s, 3H). 6-(3- fluoro -4- methoxyphenyl )-1- methyl -5- Nitro -1H- Indazole. To a solution of 6-bromo-1-methyl-5-nitro-1H-indazole (0.300 g, 1.17 mmol) and (3-fluoro-4-methoxyphenyl)boronic acid (0.209 g, 1.23 mmol) in dioxane (3 mL) was added cesium carbonate (1.146 g, 3.52 mmol) and dichloro(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloromethane adduct (0.096 g, 0.120 mmol). The resulting mixture was stirred under nitrogen at 110 °C for 12 hours. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure using a water pump. The residue was purified by preparative HPLC to give 6-(3-fluoro-4-methoxyphenyl)-1-methyl-5-nitro-1H-indazole (0.100 g, 0.332 mmol, 28% yield). 1 1H NMR (400 MHz, CDCl3) δ 8.32 (s, 1H), 8.10 (s, 1H), 7.25 (s, 1H), 7.07 (dd, J = 2.0, 11.6 Hz, 1H), 7.01 - 6.92 (m, 2H), 4.06 (s, 3H), 3.88 (s, 3H); MS (ESI) m / z: 301.8[M+1] + . 6-(3- Fluoro -4- Methoxyphenyl )-1- Methyl -1H- Indazole -5- Amine. To a solution of 6-(3-fluoro-4-methoxyphenyl)-1-methyl-5-nitro-1H-indazole (0.080 g, 0.270 mmol) in ethanol (0.6 mL) and water (0.2 mL) was added ammonium chloride (0.143 g, 2.66 mmol) and ferrous powder (0.148 g, 2.66 mmol). The resulting mixture was stirred at 70 °C for 12 h. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure to give 6-(3-fluoro-4-methoxyphenyl)-1-methyl-1H-indazol-5-amine (0.070 g, 0.258 mmol, 97% yield). 1 H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 0.8 Hz, 1H), 7.21 (d, J = 2.0 Hz, 1H), 7.18 - 7.15 (m, 1H), 7.06 (s, 1H), 7.01 (d, J = 8.4 Hz, 1H), 6.94 (s, 1H), 3.94 (s, 3H), 3.89 (s, 3H); MS (ESI) m / z: 272.4[M+1] + 。 2-(2,6- bis(oxo)piperidine -3- yl )-4-((6-(3- fluoro -4- methoxyphenyl )-1- methyl -1H- indazole -5- yl ) amino ) isoindoline -1,3- dione. To a solution of 6-(3-fluoro-4-methoxyphenyl)-1-methyl-1H-indazol-5-amine (0.070 g, 0.260 mmol) and 4-bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (0.091 g, 0.270 mmol) in dioxane (2 mL) was added potassium carbonate (0.107 mg, 0.770 mmol) and chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) (0.020 g, 0.030 mmol). The resulting mixture was stirred under nitrogen at 110 °C for 12 hours. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by preparative HPLC and preparative TLC (petroleum ether:ethyl acetate 1:1) to give 2-(2,6-dioxopiperidin-3-yl)-4-((6-(3-fluoro-4-methoxyphenyl)-1-methyl-1H-indazol-5-yl)amino)isoindoline-1,3-dione (53 mg, 0.098 mmol, 38% yield). 1 H NMR (400 MHz, DMSO-d 6 ) δ 11.17 (s, 1H), 8.29 (s, 1H), 8.13 (s, 1H), 7.88 (s, 1H), 7.79 (s, 1H), 7.49 (s, 1H), 7.46 (dd, J = 2.4, 4.8 Hz, 1H), 7.34 (d, J = 8.0 Hz, 1H), 7.23 - 7.18 (m, 1H), 7.12 (d, J = 7.2 Hz, 1H), 6.85 (d, J = 8.8 Hz, 1H), 5.14 (dd, J = 5.2, 12.8 Hz, 1H), 4.16 (s, 3H), 3.87 (s, 3H), 2.99 - 2.90 (m, 1H), 2.69 - 2.63 (m, 2H), 2.10 (dd, J = 5.2, 10.8 Hz, 1H); MS (ESI) m / z: 528.1 [M+1] + . Example 10 : 2-(2,6- dioxopiperidine -3- base )-4-((5-(2- fluoro -6- methylphenoxy )-1- methyl -1H- indazole -4- group ) amino ) isoindoline -1,3- dione 5-(2- fluoro -6- methylphenoxy )-1- methyl -4- nitro -1H- indazole. To a solution of 2-fluoro-6-methyl-phenol (0.1 g, 0.79 mmol) in N, N-dimethylformamide (3 mL) was added 5-fluoro-1-methyl-4-nitro-indazole (0.154 g, 0.79 mmol), cesium carbonate (0.515 g, 1.59 mmol), and the mixture was stirred at 90 °C for 12 hours. The mixture was diluted with water, extracted with ethyl acetate (10 ml × 3), and the separated organic layer was washed with brine (30 ml) and dried over anhydrous sodium sulfate. The organic layer was filtered and the filtrate was concentrated to give the crude product 5-(2-fluoro-6-methyl-phenoxy)-1-methyl-4-nitro-indazole (190 mg, 0.630 mmol, 79% yield). MS (ESI) m / z: 301.8 [M+1] + 5-(2- fluoro -6- methylphenoxy )-1- methyl -1H- indazole -4- Amine. To a solution of 5-(2-fluoro-6-methyl-phenoxy)-1-methyl-4-nitro-indazole (0.19 g, 0.63 mmol) in ethanol (3 mL) and water (1 mL) was added iron (0.176 g, 3.15 mmol) and ammonium chloride (0.34 g, 6.31 mmol). The mixture was stirred at 80 °C for 2 hours. The mixture was filtered and the filtrate was concentrated. The residue was purified by preparative TLC (40% ethyl acetate / petroleum ether) to give 5-(2-fluoro-6-methyl-phenoxy)-1-methyl-indazol-4-amine (50 mg, 0.184 mmol, 29% yield). 2-(2,6- bis(oxypiperidine) -3- yl )-4-((5-(2- fluoro -6- methylphenoxy )-1- methyl -1H- indazole -4- yl ) amino ) isoindoline -1,3- dione. To a solution of 5-(2-fluoro-6-methylphenoxy)-1-methyl-1H-indazol-4-amine (0.05 g, 0.18 mmol) in 1,4-dioxane (3 mL) was added 4-bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (0.062 g, 0.18 mmol), potassium carbonate (0.05 g, 0.37 mmol), and chloro(2-dicyclohexylphosphino-2,4,6-triisopropyl-1,1-biphenyl)[2-(2-amino-1,1-biphenyl)]palladium(II) (0.014 g, 0.02 mmol). The mixture was stirred under nitrogen at 110 °C for 12 h. The mixture was filtered and the filtrate was concentrated. The residue was purified by preparative HPLC to give 2-(2,6-dioxopiperidin-3-yl)-4-[[5-(2-fluoro-6-methylphenoxy)-1-methyl-1H-indazol-4-yl]amino]isoindoline-1,3-dione (13 mg, 0.025 mmol, 13% yield) and 2-(2,6-dioxopiperidin-3-yl)-4-[[5-(2-fluoro-6-methylphenoxy)-1-methyl-1H-indazol-4-yl]amino]isoindoline-1,3-dione (3 mg, 0.005 mmol, 3% yield). 1 H NMR (400 MHz, DMSO- d 6 ) δ 11.12 (s, 1H), 8.38 (s, 1H), 7.83 (s, 1H), 7.60 - 7.46 (m, 2H), 7.30 - 7.27 (m, 1H), 7.15 - 7.13 (m, 3H), 6.96 - 6.86 (m, 2H), 5.16 - 5.11 (m, 1H), 4.05 (s, 3H), 2.90 - 2.80 (m, 1H), 2.63 - 2.58 (m, 2H), 2.18 (s, 3H), 2.08 - 2.00 (m, 1H); MS (ESI) m / z: 528.2 [M+ 1] + 。 Example 11 : 2-(2,6- Dioxopiperidine -3- yl )-4-((4- Methyl -1-( Tetrahydro -2H- Pyran -4- yl )-1H- Indazole -5- yl ) Amino ) Isoindoline -1,3- Dione 5- Bromo -4- Methyl -1-( Tetrahydro -2H- Pyran -4- yl )-1H- Indazole. To a solution of 5-bromo-4-methyl-1H-indazole (0.2 g, 0.95 mmol) in N, N-dimethylformamide (5 mL) was added cesium carbonate (0.924 g, 2.84 mmol), 4-iodotetrahydropyran (0.6 g, 2.84 mmol), and the mixture was stirred at 135 °C for 24 h. The mixture was diluted with 20 ml of water and extracted with ethyl acetate (20 ml × 3). The combined organic layers were washed with saturated brine (50 ml), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated, and the residue was purified by silica gel preparative TLC (50% ethyl acetate / petroleum ether) to give 5-bromo-4-methyl-1-tetrahydropyran-4-yl-indazole (100 mg, 0.338 mmol, 35% yield). 1 H NMR (400 MHz, CDCl 3) δ 7.95 (s, 1H), 7.44 - 7.37 (m, 2H), 4.68 - 4.64 (m, 1H), 4.19 - 4.16 (m, 2H), 3.64 - 3.58 (m, 2H), 2.57 (s, 3H), 2.27 - 2.23 (m, 4H); MS (ESI) m / z: 295.1 [M+1] + 。 2-(2,6- bis(oxypiperidine) -3- yl )-4-((4- methyl -1-( tetrahydro -2H- pyran -4- yl )-1H- indazole -5- yl ) amino ) isoindoline -1,3- dione. To a solution of 5-bromo-4-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-indazole (0.1 g, 0.34 mmol) in 1,4-dioxane (3 mL) was added 4-amino-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (0.101 g, 0.37 mmol), potassium carbonate (0.09 g, 0.68 mmol), and chloro(2-dicyclohexylphosphino-2,4,6-triisopropyl-1,1'-biphenyl)[2-(2-aminobiphenyl-1-yl)]palladium(II) (0.026 g, 0.03 mmol). The mixture was stirred under nitrogen at 110 °C for 12 hours. The mixture was filtered and the filtrate was concentrated. The residue was purified by preparative HPLC to give 2-(2,6-dioxopiperidin-3-yl)-4-[(4-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-indazol-5-yl)amino]isoindoline-1,3-dione (65 mg, 0.134 mmol, 39% yield) and 2-(2,6-dioxopiperidin-3-yl)-4-[(4-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-indazol-5-yl)amino]isoindoline-1,3-dione (3 mg, 0.006 mmol, 2% yield). 1 H NMR (400 MHz, DMSO- d 6 ) δ 11.13 (s, 1H), 8.20 - 8.19 (m, 2H), 7.66 - 7.64 (m, 1H), 7.50 - 7.46 (m, 1H), 7.30 - 7.28 (m, 1H), 7.14 - 7.12 (m, 1H), 6.64 - 6.62 (m, 1H), 5.15 - 5.10 (m, 1H), 4.92 - 4.88 (m, 1H), 4.04 - 4.00 (m, 2H), 3.60 - 3.55 (m, 2H), 2.90 - 2.85 (m, 1H), 2.60 - 2.55 (m, 2H), 2.40 (s, 3H), 2.20 - 2.12 (m, 3H), 1.92 - 1.88 (m, 2H); MS (ESI) m / z: 488.3 [M+1] + 。 Example 12 : 2-(2,6- dioxopiperidinyl -3- group )-4-((6- methoxy -1-( tetrahydro -2H- pyran -4- group )-1H- indazole -5- group ) amino ) isoindoline -1,3- dione 5- bromo -6- methoxy -1- tetrahydropyran -4- group - indazole. To a solution of 5-bromo-6-methoxy-1H-indazole (0.3 g, 1.32 mmol) in dimethylformamide (4 mL) was added 4-iodotetrahydropyran (0.56 g, 2.64 mmol) and cesium carbonate (1.2 g, 3.96 mmol). The mixture was stirred at 135 °C for 24 hours. The mixture was extracted with ethyl acetate (30 mL × 3), and the combined organic layers were washed with saturated brine (60 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated. The crude product was purified by preparative TLC (petroleum ether:ethyl acetate 3:1) to give 5-bromo-6-methoxy-1-tetrahydropyran-4-yl-indazole (60 mg, 0.192 mmol, 15% yield). 1 H NMR (400 MHz, DMSO- d 6) δ 7.98 (s, 1H), 7.94 (s, 1H), 7.38 (s, 1H), 4.91 - 4.85 (m, 1H), 4.05 - 3.99 (m, 2H), 3.94 (s, 3H), 3.59 - 3.52 (m, 2H), 2.14 - 2.04 (m, 2H), 1.88 - 1.84 (m, 2H); MS (ESI) m / z: 313.3 [M+1] + 。 2-(2,6- bis(oxo) -3- piperidinyl )-4-[(6- methoxy -1- tetrahydropyranyl -4- -yl - indazolyl -5- -yl ) amino ] isoindoline -1,3- dione. To a solution of 5-bromo-6-methoxy-1-tetrahydropyran-4-yl-indazole (0.06 g, 0.19 mmol) in 1,4-dioxane (2 mL) was added potassium carbonate (0.09 g, 0.57 mmol) and chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)(2'-amino-1,1'-biphenyl-2-yl)palladium(II) (0.02 g, 0.02 mmol) and 4-amino-2-(2,6-bis(oxo)-3-piperidinyl)isoindoline-1,3-dione (0.08 g, 0.29 mmol). The mixture was stirred at 110 °C for 12 h. The mixture was concentrated under reduced pressure. The residue was purified by preparative HPLC to give 2-(2,6-bis(oxo)-3-piperidinyl)-4-[(6-methoxy-1-tetrahydropyran-4-yl-indazol-5-yl)amino]isoindoline-1,3-dione (52 mg, 0.103 mmol, 53% yield). 1 HNMR (400 MHz, DMSO- d 6 ) δ 11.13 (s, 1H), 8.24 (s, 1H), 7.96 (s, 1H), 7.76 (s, 1H), 7.59 (t, J = 8.4 Hz, 1H), 7.42 (s, 1H), 7.3 (d, J = 8.4 Hz, 1H), 7.2 (d, J = 8 Hz, 1H), 5.15 - 5.10 (m, 1H), 4.92 - 4.87 (m, 1H), 4.04 - 4.01 (m, 2H), 3.94 (s, 3H), 3.61 - 3.55 (m, 2H), 2.95 - 2.86 (m, 1H), 2.66 - 2.55 (m, 2H), 2.18 - 2.05 (m, 3H), 1.90 - 1.87 (m, 2H); MS (ESI) m / z: 504.3 [M+1] + 。 Example 13 : 2-(2,6- bis(oxo) -3- piperidinyl )-4-[[1- methyl -5-(2- methyl -4- pyridinyl ) indazole -6- yl ] amino ] isoindoline -1,3- dione 5- bromo -1- methyl -6- nitro - Indazole At 0 °C, sodium hydride (0.363 g, 9.09 mmol) was added to a solution of 5-bromo-6-nitro-1 H-indazole (2.0 g, 8.26 mmol) in DMF (20 mL). The mixture was stirred at 0 °C for 0.5 h. Methyl iodide (1.17 g, 8.26 mmol) was added to the mixture. The mixture was stirred at 25 °C for 12 h. Water (50 mL) was added to the mixture and it was extracted with ethyl acetate (50 mL × 3). The combined organic layers were washed with brine (50 mL × 1), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The resulting residue was purified by semi-preparative reversed-phase HPLC to give 5-bromo-1-methyl-6-nitro-indazole (1.20 g, 4.69 mmol, 57% yield). 1 H NMR (400 MHz, DMSO- d 6 ) δ 8.56 (s, 1H), 8.32 (s, 1H), 8.21 (d, J = 0.8 Hz, 1H), 4.12 (s, 3H); MS (ESI) m / z: 256.1[M+1] + . 1- Methyl -5-(2- Methyl -4- Pyridyl )-6- Nitro - Indazole To a solution of 5-bromo-1-methyl-6-nitro-indazole (0.300 g, 1.17 mmol) in 1,4-dioxane (3 mL) and water (0.6 mL) was added 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.385 g, 1.76 mmol), potassium carbonate (0.485 g, 3.51 mmol), and dichloro(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) (0.096 g, 0.12 mmol). The mixture was stirred under nitrogen at 100 °C for 12 h. The mixture was filtered and concentrated. The residue was purified by preparative TLC (50% ethyl acetate / petroleum ether) to give 1-methyl-5-(2-methyl-4-pyridyl)-6-nitro-indazole (0.290 g, 1.08 mmol, 92% yield). MS (ESI) m / z: 269.1[M+1] + 1- methyl -5-(2- methyl -4- pyridyl ) indazole -6- amine. To a solution of 1-methyl-5-(2-methyl-4-pyridyl)-6-nitro-indazole (0.290 g, 1.08 mmol) in ethanol (3 mL) and water (1.5 mL) was added iron powder (0.182 g, 3.24 mmol) and ammonium chloride (0.286 g, 5.41 mmol). The mixture was stirred at 80 °C for 2 h. The mixture was filtered and concentrated in vacuo. The resulting residue was purified by preparative TLC (100% ethyl acetate) to give 1-methyl-5-(2-methyl-4-pyridyl)indazol-6-amine (0.130 g, 0.54 mmol, 50% yield). 1 HNMR (400MHz, DMSO- d 6 ) δ 8.46 (d, J= 5.2 Hz, 1H), 7.78 (s, 1H), 7.39 (s, 1H), 7.32 (s, 1H), 7.25 (d, J = 5.2 Hz, 1H), 6.70 (s, 1H), 5.09 (s, 2H), 3.85 (s, 3H), 2.50 (s, 3H); MS (ESI) m / z: 239.2[M+1] + 。 3-[[1- methyl -5-(2- methyl -4- pyridinyl ) indazole -6- yl ] amino ] benzene -1,2- dimethyl phthalate. To a solution of 1-methyl-5-(2-methyl-4-pyridinyl)indazol-6-amine (0.120 g, 0.50 mmol) in 1,4-dioxane (2 mL) was added dimethyl 3-bromobenzene-1,2-dicarboxylate (0.165 g, 0.60 mmol), potassium carbonate (0.208 g, 1.51 mmol), and chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)(2′-amino-1,1′-biphenyl-2-yl)palladium(II) (0.043 g, 0.05 mmol). The mixture was stirred under nitrogen at 110 °C for 12 h. The mixture was filtered and concentrated. The residue was purified by semi-preparative reverse-phase HPLC to afford dimethyl 3-[[1-methyl-5-(2-methyl-4-pyridinyl)indazol-6-yl]amino]benzene-1,2-dicarboxylate (0.200 g, 0.46 mmol, 92% yield). MS (ESI) m / z: 431.2[M+1] + 。 2-(2,6- dioxy -3- piperidinyl )-4-[[1- methyl -5-(2- methyl -4- Pyridyl ) Indazole -6- yl ] Amino ] Isoindoline -1,3- dione. To a solution of dimethyl 3-[[1-methyl-5-(2-methyl-4-pyridyl)indazol-6-yl]amino]benzene-1,2-dicarboxylate (0.100 g, 0.23 mmol) in pyridine (1 mL) was added 3-aminopiperidine-2,6-dione hydrochloride (0.042 g, 0.26 mmol) and lithium iodide (0.091 g, 0.70 mmol). The mixture was stirred at 120 °C for 12 hours. The mixture was concentrated in vacuo. The resulting residue was purified by semi-preparative reverse-phase HPLC to give the product 2-(2,6-dioxido-3-piperidyl)-4-[[1-methyl-5-(2-methyl-4-pyridyl)indazol-6-yl]amino]isoindoline-1,3-dione (52 mg, 0.104 mmol, 45% yield). 1 H NMR (400MHz, DMSO- d 6 ) δ 11.11 (s, 1H), 8.41 - 8.35 (m, 2H), 8.12 (s, 1H), 7.86 (s, 1H), 7.78 (s, 1H), 7.52 - 7.45 (m, 1H), 7.39 (s, 1H), 7.29 (d, J= 5.2 Hz, 1H), 7.17 - 7.09 (m, 2H), 5.10 - 5.03 (m, 1H), 4.06 (s, 3H), 2.90 - 2.82 (m, 1H), 2.61 - 2.57 (m, 2H), 2.43 (s, 3H), 2.07 - 1.99 (m, 1H); MS (ESI) m / z: 495.1[M+1] + 。 Example 14 : 2-(2,6- 2,2,6,6 - Tetramethylpiperidine - 3 - yl -3- yl )-4-((5-(3- fluoro -4- methoxyphenyl )-1- methyl -1H- benzo [d] imidazole -6- yl ) amino ) isoindoline -1,3- dione 5-(3- fluoro -4- methoxyphenyl )-1- methyl -6- nitro -1H- benzo [d] imidazole . To a solution of 5 - bromo - 1 - methyl - 6 - nitro - 1H - benzo[d]imidazole (0.060 g, 0.23 mmol) and (3 - fluoro - 4 - methoxyphenyl)boronic acid (0.048 g, 0.28 mmol) in dioxane (0.5000 mL) was added potassium carbonate (0.096 g, 0.70 mmol) and dichloro(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) (0.018 g, 0.03 mmol). The resulting mixture was stirred under nitrogen at 110 °C for 12 hours. The mixture was filtered and the filtrate was concentrated in vacuo. The residue was purified by preparative TLC (petroleum ether:ethyl acetate, 1:2) to give 5 - (3 - fluoro - 4 - methoxyphenyl)-1 - methyl - 6 - nitro - 1H - benzo[d]imidazole (0.054 g, 0.18 mmol, 76% yield). MS (ESI) m / z: 302.1[M+1] + 5-(3- fluoro -4- 4-Methoxyphenyl )-1- Methyl -1H- Benzo [d] Imidazole -6- Amine. To a solution of 5-(3-fluoro-4-methoxyphenyl)-1-methyl-6-nitro-1H-benzo[d]imidazole (0.050 g, 0.17 mmol) in ethanol (0.3 mL) and water (0.1 mL) was added iron powder (0.050 g, 0.90 mmol) and ammonium chloride (0.090 g, 1.67 mmol). The resulting mixture was stirred at 70 °C for 12 hours. The mixture was filtered and the filtrate was concentrated in vacuo. The crude product was purified by preparative HPLC to give 5-(3-fluoro-4-methoxyphenyl)-1-methyl-1H-benzo[d]imidazole-6-amine (0.051 g, 0.188 mmol, 100% yield). 1 H NMR (400 MHz, CDCl 3 ) δ 7.56 (s, 1 H), 7.19 (s, 1 H), 7.14 - 7.01 (m, 3 H), 6.74 (s, 1 H), 5.00 - 5.52 (m, 2 H), 3.92 (s, 3 H), 3.89 (s, 3H); MS (ESI) m / z: 272.1[M+1] + 。 3-((5-(3- Fluoro -4- 4-Methoxyphenyl )-1- Methyl -1H- Benzo [d] Imidazole -6- yl ) Amino ) Dimethyl phthalate. To a solution of 5-(3-fluoro-4-methoxyphenyl)-1-methyl-1H-benzo[d]imidazol-6-amine (0.041 g, 0.15 mmol) and dimethyl 3-bromophthalate (0.045 g, 0.16 mmol) in dioxane (2 mL) was added methanesulfonato(2-dicyclohexylphosphino-2,6-diisopropoxy-1,1-biphenyl)(2-amino-1,1'-biphenyl-2-yl)palladium(II) (0.012 g, 0.01 mmol) and cesium carbonate (0.148 g, 0.46 mmol). The resulting mixture was stirred under nitrogen at 110 °C for 12 h. The mixture was filtered and the filtrate was concentrated in vacuo. The residue was purified by preparative TLC (petroleum ether:ethyl acetate 1:1) to give dimethyl 3-((5-(3-fluoro-4-methoxyphenyl)-1-methyl-1H-benzo[d]imidazol-6-yl)amino)phthalate (0.041 g, 0.088 mmol, 58% yield). MS (ESI) m / z: 464.2 [M+1] + 2-(2,6- bisoxopiperidine -3- yl )-4-((5-(3- fluoro -4- methoxyphenyl )-1- methyl -1H- benzo [d] imidazole -6- yl ) amino ) isoindoline -1,3- dione. To a solution of dimethyl 3-((5-(3-fluoro-4-methoxyphenyl)-1-methyl-1H-benzo[d]imidazol-6-yl)amino)phthalate (0.035 g, 0.08 mmol) and 3-aminopiperidine-2,6-dione hydrochloride (0.035 g, 0.21 mmol) in pyridine (1.5 mL) was added lithium iodide (0.049 mg, 0.38 mmol). The resulting mixture was stirred at 130 °C for 12 h. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The crude product was purified by preparative HPLC to give 2-(2,6-dioxopiperidin-3-yl)-4-((5-(3-fluoro-4-methoxyphenyl)-1-methyl-1H-benzo[d]imidazol-6-yl)amino)isoindoline-1,3-dione (33 mg, 0.063 mmol, 84% yield). 1 H NMR (400 MHz, DMSO- d 6 ) δ 11.11 (s, 1H), 8.94 - 8.90 (m, 1H), 8.32 (s, 1H), 7.90 (s, 1H), 7.75 (s, 1H), 7.49 - 7.40 (m, 1H), 7.39 - 7.37 (m, 1H), 7.28 (d, J= 1.6 Hz, 1H), 7.18 - 7.14 (m, 2H), 7.28 (d, J= 2.4 Hz, 1H), 5.08 (dd, J= 5.6, 13.2 Hz, 1H), 3.96 (s, 3H), 3.82 (s, 3H), 2.92 - 2.89 (m, 1H), 2.86 - 2.84 (m, 2H), 2.10 - 2.01 (m, 1H); MS (ESI) m / z: 528.0 [M+1] + 。 Example 15 : 2-(2,6- dioxopiperidine -3- yl )-4-((6-(2- methylpyridine -4- Base )-1-( Tetrahydro -2H- Pyran -4- yl )-1H- Indazole -5- yl ) Amino ) Isoindoline -1,3- Dione 6- Bromo -5- Nitro -1-( Tetrahydro -2H- Pyran -4- yl )-1H- Indazole. To a solution of 6-bromo-5-nitro-1H-indazole (1.0 g, 4.13 mmol) in N,N-dimethylacetamide (10 mL) was added potassium carbonate (1.7 g, 12.4 mmol), 4-iodotetrahydropyran (1.05 g, 4.96 mmol). The solution was stirred at 135 °C for 1 hour. The suspension was filtered and the filtrate was concentrated. The residue was purified by preparative TLC (petroleum ether:ethyl acetate, 2:1) to give 6-bromo-5-nitro-1-tetrahydropyran-4-yl-indazole (200 mg, 0.613 mmol, 14% yield). 1 H NMR (400 MHz,CDCl 3 ) δ 8.41 (s, 1H), 8.09 (s, 1H), 7.59 (s, 1H), 4.56 - 4.53 (m, 1H), 4.14 - 4.10 (m, 2H), 3.60 - 3.53 (m, 2H), 2.36 - 2.32 (m, 2H), 1.94 - 1.90 (m, 2H); MS (ESI) m / z 326.2 [M+1] + . 6-(2- methylpyridine -4- yl )-5- nitro -1-( tetrahydro -2H- pyran -4- yl )-1H- indazole. To a solution of 6-bromo-5-nitro-1-tetrahydropyran-4-yl-indazole (0.220 g, 0.670 mmol) in 1,4-dioxane (10 mL) was added 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.177 g, 0.810 mmol), potassium carbonate (0.279 g, 2.02 mmol), and dichloromethane complex of [1,1-bis(diphenylphosphino)ferrocene]palladium(II) chloride (0.055 g, 0.070 mmol). The mixture was stirred under nitrogen at 110 °C for 12 hours. The mixture was concentrated in vacuo. The residue was purified by preparative TLC (petroleum ether:ethyl acetate 3:1) to give 6-(2-methyl-4-pyridyl)-5-nitro-1-tetrahydropyran-4-yl-indazole (160 mg, 0.472 mmol, 70% yield). 1 H NMR (400 MHz,CDCl 3 ) δ 8.79 (d, J= 6.0 Hz, 1H), 8.70 (s, 1H), 8.27 (s, 1H), 7.58 (d, J= 5.2 Hz, 1H), 7.50 (s, 1H), 7.36 (s, 1H), 4.65 - 4.63 (m, 1H), 4.14 - 4.10 (m, 2H), 3.58 - 3.52 (m, 2H), 2.58 (s, 3H), 2.40 - 2.36 (m, 2H), 1.95 - 1.92 (m, 2H); MS (ESI) m / z 339.2 [M+1] + . 6-(2- Methylpyridine -4- yl )-1-( tetrahydro -2H- pyran -4- yl )-1H- indazole -5- amine. To a solution of 6-(2-methyl-4-pyridyl)-5-nitro-1-tetrahydropyran-4-yl-indazole (0.160 g, 0.4700 mmol) in ethanol (10 mL) was added a solution of iron powder (0.265 g, 4.73 mmol) and ammonium chloride (0.255 g, 4.73 mmol) in water (2 mL). The solution was stirred at 90 °C for 2 hours. The suspension was filtered and the filtrate was extracted with dichloromethane (100 ml × 2). The combined organic phases were washed with brine (50 ml), dried over sodium sulfate and filtered. The filtrate was concentrated to give 6-(2-methyl-4-pyridyl)-1-tetrahydropyran-4-yl-indazol-5-amine (100 mg, 0.324 mmol, 68% yield). MS (ESI) m / z 309.4 [M+1] + dimethyl -3-((6-(2- methylpyridine -4- yl )-1-( tetrahydro -2H- pyran -4- yl )-1H- indazole -5- yl ) amino ) phthalate. To a solution of 6-(2-methyl-4-pyridinyl)-1-tetrahydropyran-4-yl-1H-indazol-5-amine (0.10 g, 0.320 mmol) in 1,4-dioxane (5 mL) was added dimethyl 3-bromobenzene-1,2-dicarboxylate (0.106 g, 0.390 mmol), potassium carbonate (0.134 g, 0.970 mmol), and chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)(2′-amino-1,1′-biphenyl-2-yl)palladium(II) (0.027 g, 0.030 mmol). The mixture was stirred under nitrogen at 110 °C for 12 h. The solution was concentrated and the residue was purified by preparative HPLC to give dimethyl 3-[[6-(2-methyl-4-pyridinyl)-1-tetrahydropyran-4-yl-1H-indazol-5-yl]amino]benzene-1,2-dicarboxylate (100 mg, 0.199 mmol, 61% yield). 1 H NMR (400 MHz, CDCl 3 ) δ 8.73 (s, 1H), 8.15 (s, 1H), 8.10 (s, 1H), 7.81 (s, 1H), 7.71 (brs, 2H), 7.58 (brs, 1H),7.24 - 7.20 (m, 1H), 7.01 - 6.99 (m,1H), 6.83 (d, J= 8.4 Hz, 1H), 4.75 - 4.72 (m, 2H), 4.22 - 4.20 (m, 2H), 3.92 (s, 3H), 3.90 (s, 3H), 3.70 - 3.65 (m, 2H), 2.65 (s, 3H), 2.49 - 2.47 (m, 2H), 2.07 - 2.04 (m, 2H); MS (ESI) m / z 501.3 [M+1] + 。 2-(2,6- bis(oxypiperidine) -3- yl )-4-((6-(2- methylpyridine -4- yl )-1-( tetrahydro -2H- Pyran -4- yl )-1H- Indazole -5- yl ) Amino ) Isoindoline -1,3- Dione. To a solution of dimethyl 3-[[6-(2-methyl-4-pyridyl)-1-tetrahydropyran-4-yl-indazol-5-yl]amino]benzene-1,2-dicarboxylate (0.10 g, 0.200 mmol) in pyridine (2 mL) was added 3-aminopiperidine-2,6-dione hydrochloride (0.036 g, 0.220 mmol) and lithium iodide (0.053 g, 0.400 mmol). The mixture was stirred at 120 °C for 12 h. The mixture was concentrated in vacuo and the residue was purified by semi-preparative reverse-phase HPLC to give 2-(2,6-dioxido-3-piperidyl)-4-[[6-(2-methyl-4-pyridyl)-1-tetrahydropyran-4-yl-indazol-5-yl]amino]isoindoline-1,3-dione (45 mg, 0.073 mmol, 36% yield). 1 H NMR (400 MHz, DMSO- d 6 ) δ 11.11 (s, 1H), 8.60 (d, J= 5.6 Hz, 1H), 8.42 (s, 1H), 8.21 (s, 1H), 8.07 (s, 1H), 7.92 (s, 1H), 7.85 (brs, 1H), 7.76 - 7.74 (m, 1H), 7.41 (d, J= 8.0 Hz, 1H), 7.08 (d, J= 7.8 Hz, 1H), 6.72 (d, J = 8.4 Hz, 1H), 5.10 - 5.03 (m, 2H), 4.06 - 4.02 (m, 2H), 3.60 - 3.55 (m, 2H), 2.91 - 2.88 (m, 1H), 2.67 - 2.66 (m, 2H), 2.51 (s, 3H), 2.20 - 2.15 (m, 2H), 2.09 - 2.00 (m, 1H), 1.95 - 1.92 (m, 2H); MS (ESI) m / z 565.3 [M+1] + 。 Example 16 : 4-((1- cyclopropyl -5-(2- methylpyridine -4- yl )-1H- benzo [d] imidazole -6- yl ) amino )-2-(2,6- bis(oxo)piperidine -3- yl ) isoindoline -1,3- dione 6- bromo -5- nitro -1H- benzimidazole. Potassium nitrate (5.18 g, 60.90 mmol) was added portionwise to a solution of 5-bromo-1H-benzimidazole (10.0 g, 50.75 mmol) in sulfuric acid (50 mL, 2967.60 mmol) at 0 °C. The mixture was stirred at 25 °C for 1 h. The reaction mixture was poured into 500 mL of ice water, and the pH of the combined aqueous layer was adjusted to pH 7 by adding 6 N aqueous sodium hydroxide solution. The resulting precipitated solid was collected by filtration and purified by preparative HPLC to give 5-bromo-6-nitro-1H-benzimidazole (5.10 g, 21.07 mmol, 41% yield). 1 H NMR (400 MHz, DMSO- d 6 ) δ 8.54 (s, 1H), 8.36 (s, 1H), 8.08 (s, 1H); MS (ESI) m / z: 244.0 [M] + 。 5- bromo -1- cyclopropyl -6- nitro -1H- benzimidazole. To a solution of 6-bromo-5-nitro-1H-benzimidazole (0.600 g, 2.48 mmol) in dichloroethane (20 mL) was added cyclopropylboronic acid (0.430 g, 4.96 mmol), 2-(2-pyridyl)pyridine (0.388 g, 2.48 mmol), copper(II) diacetate (0.394 g, 2.48 mmol), and sodium carbonate (0.525 g, 4.96 mmol). The mixture was stirred at 70 °C for 12 h under air. The mixture was filtered and the filtrate was concentrated. The residue was purified by silica gel preparative TLC (50% ethyl acetate / petroleum ether) to give 6-bromo-1-cyclopropyl-5-nitrobenzimidazole (0.290 g, 1.02 mmol, 41% yield). MS (ESI) m / z: 283.3 [M+1] + 1- cyclopropyl -5-(2- methylpyridine -4- group )-6- nitro -1H- -benzimidazole. To a solution of 6-bromo-1-cyclopropyl-5-nitro-1H-benzimidazole (0.280 g, 0.99 mmol) in 1,4-dioxane (4 mL) and water (1 mL) was added 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.217 g, 0.99 mmol), dichloro(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) (0.080 g, 0.10 mmol), and potassium carbonate (0.274 g, 1.99 mmol). The mixture was stirred under nitrogen at 100 °C for 12 h. The mixture was filtered and the filtrate was concentrated. The residue was purified by silica gel preparative TLC (80% ethyl acetate / petroleum ether) to give 1-cyclopropyl-6-(2-methyl-4-pyridyl)-5-nitro-1H-benzimidazole (0.200 g, 0.679 mmol, 68% yield). MS (ESI) m / z: 295.1 [M+1] + 1- cyclopropyl -5-(2- methylpyridine -4- group )-1H- -benzimidazole -6- -amine. To a solution of 1-cyclopropyl-5-(2-methyl-4-pyridyl)-6-nitro-1H-benzimidazole (0.200 g, 0.68 mmol) in ethanol (6 mL) and water (2 mL) was added iron (0.189 g, 3.40 mmol) and ammonium chloride (0.367 g, 6.80 mmol). The mixture was stirred at 80 °C for 1 h. The mixture was filtered and the filtrate was concentrated. The resulting residue was purified by preparative HPLC to give 3-cyclopropyl-6-(2-methyl-4-pyridyl)benzimidazole-5-amine (0.070 g, 0.264 mmol, 38% yield). MS (ESI) m / z: 265.1 [M+1] + 3-((1- cyclopropyl -5-(2- Methylpyridine -4- yl )-1H- Benzo [d] Imidazole -6- yl ) Amino ) Dimethyl phthalate. To a solution of 3-cyclopropyl-6-(2-methyl-4-pyridinyl)-1H-benzo[d]imidazol-5-amine (0.050 g, 0.19 mmol) in 1,4-dioxane (4 mL) was added dimethyl 3-bromobenzene-1,2-dicarboxylate (0.057 g, 0.21 mmol), potassium carbonate (0.078 g, 0.57 mmol), and chloro(2-dicyclohexylphosphino-2,4,6-triisopropyl-1,1-biphenyl)[2-(2-amino-1,1-biphenyl)]palladium(II) (0.015 g, 0.02 mmol). The mixture was stirred under nitrogen at 110 °C for 12 h. The mixture was filtered and the filtrate was concentrated. The residue was purified by preparative HPLC to give dimethyl 3-[[3-cyclopropyl-6-(2-methyl-4-pyridinyl)-1H-benzo[d]imidazol-5-yl]amino]benzene-1,2-dicarboxylate (0.030 g, 0.065 mmol, 34% yield). 1 H NMR (400 MHz, MeOD- d 4 ) δ 9.12 (brs, 1H), 8.59 - 8.58 (m, 1H), 8.08 - 8.01 (m, 1H), 8.00 - 7.98 (m, 2H), 7.82 (s, 1H), 7.28 - 7.20 (m, 2H), 6.94 - 6.93 (m, 1H), 3.85 - 3.82 (m, 6H), 3.70 (s, 1H), 3.32 - 3.30 (m, 1H), 2.74 (s, 3H), 1.31 - 1.23 (m, 4H). MS (ESI) m / z: 457.2 [M+1] + 4-((1- Cyclopropyl -5-(2- Methylpyridine -4- yl )-1H- Benzo [d] Imidazole -6- yl ) Amino )-2-(2,6- Dioxopiperidine -3- yl ) Isoindoline -1,3- Dione. To a solution of dimethyl 3-[[3-cyclopropyl-6-(2-methyl-4-pyridinyl)-1H-benzo[d]imidazol-5-yl]amino]benzene-1,2-dicarboxylate (0.030 g, 0.07 mmol) in pyridine (2 mL) was added 3-aminopiperidine-2,6-dione hydrochloride (0.016 g, 0.10 mmol) and lithium iodide (0.044 g, 0.33 mmol). The solution was stirred at 120 °C for 12 hours. The mixture was concentrated under reduced pressure. The residue was purified by preparative HPLC to give 4-[[3-cyclopropyl-6-(2-methyl-4-pyridinyl)-1H-benzo[d]imidazol-5-yl]amino]-2-(2,6-dioxo-3-piperidinyl)isoindoline-1,3-dione (9.96 mg, 0.018 mmol, 28% yield). 1 H NMR (400 MHz, DMSO- d 6) δ 11.11 (s, 1H), 8.37 - 8.33 (m, 4H), 7.75 - 7.72 (m, 2H), 7.42 - 7.40 (m, 1H), 7.36 (s, 1H), 7.26 - 7.25 (m, 1H), 7.09 - 7.08 (m, 1H), 6.90 - 6.87 (m, 1H), 5.10 - 5.06 (m, 1H), 3.56 - 3.52 (m, 1H), 2.95 - 2.85 (m, 1H), 2.58 - 2.52 (m, 2H), 2.33 (s, 3H), 2.04 - 2.02 (m, 1H), 1.11 - 1.06 (m, 4H); MS (ESI) m / z: 521.3 [M+1] + 。 Example 17 : 2-(2,6- Dioxo -3- Piperidinyl )-4-[[3- Methyl -6-(2- Methyl -4- Pyridinyl )-1,2- Benzoxazole -5- yl ] Amino ] Isoindoline -1,3- Dione 6- Bromo -3- Methyl -5- Nitro -1,2- Benzoxazole. To a solution of 6-bromo-3-methyl-1,2-benzoxazole (2.00 g, 9.43 mmol) in concentrated sulfuric acid (30 mL, 9.43 mmol) was added dropwise concentrated nitric acid (1.26 mL, 28.30 mmol) at 0 °C. The mixture was stirred at 25 °C for 2 h. The mixture was slowly poured into ice water (100 mL). The aqueous phase was extracted with ethyl acetate (60 mL × 2). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (20 - 25% ethyl acetate / petroleum ether) to give 6-bromo-3-methyl-5-nitro-1,2-benzoxazole (0.40 g, 1.56 mmol, 16% yield). 1 H NMR (400 MHz, DMSO- d 6 ) δ 8.73 (s, 1H), 8.43 (s, 1H), 2.60 (s, 3H). 3- methyl -6-(2- methyl -4- pyridinyl )-5- nitro -1,2- benzoxazole. To a solution of 6-bromo-3-methyl-5-nitro-1,2-benzoxazole (0.360 g, 1.40 mmol) in 1,4-dioxane (5 mL) was added 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.368 g, 1.68 mmol), sodium carbonate (1.4 mL, 2 M, 2.80 mmol) and dichloro(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloromethane adduct (0.098 g, 0.14 mmol). The suspension was degassed under vacuum and purged with nitrogen several times. The mixture was stirred at 80 °C for 12 h. The mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by preparative HPLC to give 3-methyl-6-(2-methyl-4-pyridinyl)-5-nitro-1,2-benzoxazole (0.260 g, 0.97 mmol, 68% yield). 1H NMR (400 MHz, CDCl3) δ 8.61 (d, J = 5.2 Hz, 1H), 8.37 (s, 1H), 7.55 (s, 1H), 7.16 (s, 1H), 7.10 (dd, J = 1.2, 5.2 Hz, 1H), 2.70 (s, 3H), 2.65 (s, 3H); MS (ESI) m / z 270.1 [M+1] + . 3- methyl -6-(2- methyl -4- Pyridyl )-1,2- Benzoxazole -5- amine. To a solution of 3-methyl-6-(2-methyl-4-pyridinyl)-5-nitro-1,2-benzoxazol-5-amine (0.060 g, 0.25 mmol, 37% yield) was added stannous chloride (0.302 g, 1.34 mmol) in hydrochloric acid (0.67 mL, 1 M, 0.67 mmol) to a solution of 3-methyl-6-(2-methyl-4-pyridinyl)-5-nitro-1,2-benzoxazol-5-amine (0.060 g, 0.25 mmol, 37% yield). The mixture was stirred at 100 °C for 1 hour. The mixture was concentrated under reduced pressure. The mixture was alkalized to pH 7-8 with ammonium hydroxide. The residue was purified by preparative TLC (ethyl acetate) to give 3-methyl-6-(2-methyl-4-pyridinyl)-1,2-benzoxazol-5-amine (0.060 g, 0.25 mmol, 37% yield). MS (ESI) m / z 240.0 [M+1]+ 2-(2,6- Dioxy -3- Piperidinyl )-4-[[3- methyl -6-(2- methyl -4- Pyridyl )-1,2- Benzoxazole -5- base ] Amine ] Isoindoline -1,3- dione. To a solution of 3-methyl-6-(2-methyl-4-pyridyl)-1,2-benzoxazol-5-amine (0.060 g, 0.25 mmol) in 1,4-dioxane (5 mL) was added 4-bromo-2-(2,6-dioxo-3-piperidyl)isoindoline-1,3-dione (0.101 g, 0.30 mmol), sodium carbonate (0.080 g, 0.75 mmol), and chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)(2'-amino-1,1'-biphenyl-2-yl)palladium(II) (0.020 g, 0.03 mmol). The suspension was degassed under vacuum and purged with nitrogen several times. The mixture was stirred at 80 °C for 12 h. The mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by preparative HPLC and preparative TLC (9% methanol / dichloromethane) to give 2-(2,6-dioxo-3-piperidyl)-4-[[3-methyl-6-(2-methyl-4-pyridyl)-1,2-benzoxazol-5-yl]amino]isoindoline-1,3-dione (4.01 mg, 0.007 mmol, 3% yield). 1 H NMR (400 MHz, DMSO- d 6 ) δ 11.11 (s, 1H), 8.46 (s, 1H), 8.39 (d, J= 5.2 Hz, 1H), 8.36 (s, 1H), 7.99 (s, 1H), 7.85 (s, 1H), 7.47 - 7.40 (m, 2H), 7.30 (d, J= 5.6 Hz, 1H), 7.10 (d, J = 7.2 Hz, 1H), 6.84 (d, J= 8.8 Hz, 1H), 5.07 (dd, J= 5.6, 12.8 Hz, 1H), 2.90 - 2.86 (m, 1H), 2.62 - 2.60 (m, 1H), 2.59 (s, 3H), 2.58 - 2.56 (m, 1H), 2.41 (s, 3H), 2.06 - 2.01 (m, 1H); MS (ESI) m / z 496.1 [M+1] + . Example 18 : 4-((1,2- Dimethyl -5-(2- Methylpyridine -4- yl )-1H- Benzo [d] Imidazole -6- yl ) Amino )-2-(2,6- Dioxopiperidine -3- yl ) Isoindoline -1,3- Dione 6- Bromo -2- Methyl -5- Nitro -1H- Benzimidazole. To a solution of 6-bromo-2-methyl-1H-benzimidazole (2.0 g, 9.48 mmol) in sulfuric acid (20 mL, 373.47 mmol) at 0 °C was added dropwise nitric acid (1.27 mL, 28.43 mmol). The mixture was stirred at 0 °C for 2 hours. The mixture was filtered and the filtrate was concentrated in vacuo. The residue was purified by preparative HPLC to give 6-bromo-2-methyl-5-nitro-1H-benzimidazole and 6-bromo-2-methyl-7-nitro-1H-benzo[d]imidazole (1.40 g, 5.47 mmol, 58% yield). 1 H NMR (400MHz, DMSO-d 6 ) δ 8.21 (s, 1H), 8.13 (s, 1H), 7.92 (s, 1H), 2.49 (s, 3H); MS (ESI) m / z: 257.8 [M+1] + . 6- bromo -1,2- dimethyl -5- nitro - benzimidazole. At 0 °C, sodium hydride (0.117 g, 2.93 mmol) was added to a solution of 6-bromo-2-methyl-5-nitro-1H-benzimidazole (0.500 g, 1.95 mmol) in tetrahydrofuran (10 mL). The mixture was stirred for 30 minutes. Iodomethane (0.25 mL, 3.91 mmol) was added and the mixture was stirred at 20 °C for 12 hours. The mixture was filtered and the filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate 1:1) to give a mixture of 6-bromo-1,2-dimethyl-5-nitro-benzimidazole and 5-bromo-1,2-dimethyl-6-nitro-benzimidazole (0.45 g, 1.67 mmol, 85% yield). MS (ESI) m / z: 270.3 [M+1] + 1,2- dimethyl -5-(2- methyl -4- pyridyl )-6- nitro - benzimidazole. To a solution of a mixture of 6-bromo-1,2-dimethyl-5-nitro-benzoimidazole and 5-bromo-1,2-dimethyl-6-nitro-benzoimidazole (0.40 g, 1.30 mmol) in 1,4-dioxane (5 mL) and water (0.50 mL) was added 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.48 g, 2.22 mmol), cesium carbonate (0.96 g, 2.96 mmol), and dichloro(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) (0.12 g, 0.15 mmol). The suspension was degassed and purged with nitrogen several times. The mixture was stirred at 110 °C for 12 h. The mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (1:1 petroleum ether / ethyl acetate) to give a mixture of 1,2-dimethyl-5-(2-methyl-4-pyridyl)-6-nitro-benzoimidazole and 1,2-dimethyl-6-(2-methyl-4-pyridyl)-5-nitro-benzoimidazole (0.40 g, 1.42 mmol, 96% yield). MS (ESI) m / z: 283.1 [M+1]+ 2,3- dimethyl -6-(2- methyl -4- pyridyl ) benzoimidazole -5- amine. To a solution of a mixture of 1,2-dimethyl-5-(2-methyl-4-pyridyl)-6-nitro-benzoimidazole and 1,2-dimethyl-6-(2-methyl-4-pyridyl)-5-nitro-benzoimidazole (0.40 g, 1.42 mmol) in water (2 mL) and ethanol (5 mL) was added iron powder (0.395 g, 7.08 mmol) and ammonium chloride (0.765 g, 14.17 mmol). The mixture was stirred at 80 °C for 2 h. The mixture was filtered and the filtrate was concentrated in vacuo. The residue was purified by preparative HPLC to give a mixture of 2,3-dimethyl-6-(2-methyl-4-pyridyl)benzoimidazole-5-amine and 2,3-dimethyl-5-(2-methyl-4-pyridyl)benzoimidazole-6-amine (0.20 g, 0.79 mmol, 56% yield). MS (ESI) m / z: 253.2 [M+1] + 3-((1,2- Dimethyl -5-(2- Pyridine -4- base )-1H- Benzo [d] Imidazole -6- base ) Amine ) dimethyl phthalate. To a solution of a mixture of 2,3-dimethyl-6-(2-methyl-4-pyridyl)benzimidazol-5-amine and 2,3-dimethyl-5-(2-methyl-4-pyridyl)benzimidazol-6-amine (0.200 g, 0.79 mmol) in 1,4-dioxane (2 mL) were added potassium carbonate (0.328 g, 2.38 mmol) and mesylate (2-dicyclohexylphosphino-2,6-diisopropoxy-1,1-biphenyl)(2-amino-1,1-biphenyl-2-yl)palladium (II) (0.066 g, 0.08 mmol) and dimethyl 3-bromobenzene-1,2-dicarboxylate (0.303 g, 1.11 mmol). The mixture was stirred at 110° C. under nitrogen for 12 hours. The mixture was filtered and the filtrate was concentrated in vacuo. The residue was purified by preparative HPLC to give dimethyl 3-[[2,3-dimethyl-6-(2-methyl-4-pyridyl)benzimidazol-5-yl]amino]benzene-1,2-dicarboxylate (0.080 g, 0.18 mmol, 22% yield). 1 H NMR (400MHz, DMSO- d 6 ) δ 8.66 (d, J= 6.0 Hz, 1H), 8.05 (s, 1H), 7.89 (s, 1H), 7.86 (s, 1H), 7.81 (d, J= 6.0 Hz, 1H), 7.73 (s, 1H), 7.28 - 7.24 (m, 1H), 7.11 (d, J = 7.2 Hz, 1H), 6.81 (d, J = 8.0 Hz, 1H), 3.84 (s, 3H), 3.78 (s, 3H), 3.69 (s, 3H), 2.75 (s, 3H), 2.61 (s, 3H); MS (ESI) m / z: 445.3 [M+1] + Dimethyl 3 - ((1,2 - dimethyl - 6 - (2 - methylpyridin - 4 - yl) - 1H - benzo[d]imidazol - 5 - yl)amino)phthalate (0.060 g, 0.13 mmol, 16.4% yield). 1 H NMR (400MHz, DMSO - d 6 ) δ 8.67 (d, J = 6.4 Hz, 1H), 8.07 (s, 1H), 8.06 (s, 1H), 7.87 (s, 1H), 7.80 (d, J = 6.0 Hz, 1H), 7.57 (s, 1H), 7.26 (t, J = 8.0 Hz, 1H), 7.15 (d, J = 6.8 Hz, 1H), 6.81 (d, J = 8.4 Hz, 1H), 3.93 (s, 3H), 3.78 (s, 3H), 3.71 (s, 3H), 2.78 (s, 3H), 2.61 (s, 3H). 4 - ((1,2 - dimethyl - 5 - (2 - methylpyridine - 4 - yl ) - 1H - benzo [d] imidazole - 6 - yl ) amino ) - 2 - (2,6 - bis(oxo)piperidine - 3 - yl ) Isoindoline -1,3- dione. To a solution of dimethyl 3-[[2,3-dimethyl-6-(2-methylpyridin-4-yl)-1H-benzo[d]imidazol-5-yl]amino]benzene-1,2-dicarboxylate (0.100 g, 0.220 mmol) in pyridine (2 mL) was added 3-aminopiperidine-2,6-dione (0.057 g, 0.450 mmol) and lithium iodide (50 mg). The suspension was stirred at 135 °C for 12 h. The solution was filtered and the filtrate was concentrated. The residue was purified by preparative HPLC to give 4-[[2,3-dimethyl-6-(2-methylpyridin-4-yl)-1H-benzo[d]imidazol-5-yl]amino]-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (66 mg, 0.120 mmol, 53% yield). 1 H NMR (400MHz, DMSO- d 6 ) δ 11.12 (s, 1H), 8.59 (d, J= 6.4 Hz, 1H), 8.54 (s, 1H), 7.92 (s, 1H), 7.88 (s, 1H), 7.83 (s, 1H), 7.77 (s, 1H), 7.49 - 7.45 (m, 1H),7.15 (d, J= 6.4 Hz, 1H), 6.82 (d, J= 8.4 Hz, 1H), 5.12 - 5.07(m,1H), 3.93 (s, 3H), 2.90 - 2.89 (m, 1H), 2.58 (s, 3H), 2.54 - 2.53 (m, 1H), 2.51 (s, 3H), 2.49 - 2.48 (m, 1H), 2.05 - 2.04 (m, 1H); MS (ESI) m / z: 509.2 [M+1] + 。 Example 19 : 4-((6- cyclopropyl -1-( tetrahydro -2H- Pyran -4- yl )-1H- Indazole -5- yl ) Amino )-2-(2,6- Dioxopiperidine -3- yl ) Isoindoline -1,3- Dione 6- Cyclopropyl -5- Nitro -1-( Tetrahydro -2H- Pyran -4- yl )-1H- Indazole. To a solution of 6-bromo-5-nitro-1-(tetrahydro-2H-pyran-4-yl)-1H-indazole (0.300 g, 0.92 mmol) in tert-amyl alcohol (4 mL) was added cyclopropylboronic acid (0.095 g, 1.11 mmol), cesium carbonate (0.900 g, 2.77 mmol) and bis(di-tert-butyl(2-amino-1,1'-biphenyl-2-yl)phosphino) palladium(II) dichloromethane adduct (0.034 g, 0.05 mmol). The suspension was degassed and purged with nitrogen. The mixture was stirred at 90 °C for 12 hours. The mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by preparative TLC (petroleum ether:ethyl acetate 3:1) to give 6-cyclopropyl-5-nitro-1-(tetrahydro-2H-pyran-4-yl)-1H-indazole (0.070 g, 0.24 mmol, 26% yield). MS (ESI) m / z: 287.8 [M+1] + 6- Cyclopropyl -1-( Tetrahydro -2H- Pyran -4- radical )-1H- indazole -5- amine. To a solution of 6-cyclopropyl-5-nitro-1-(tetrahydro-2H-pyran-4-yl)-1H-indazole (0.070 g, 0.24 mmol) in ethanol (3 mL) and water (1 mL) was added iron powder (0.136 g, 2.44 mmol) and ammonium chloride (0.132 g, 2.44 mmol). The resulting mixture was stirred at 70 °C for 12 h. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by preparative TLC (petroleum ether:ethyl acetate 1:1) to give 6-cyclopropyl-1-(tetrahydro-2H-pyran-4-yl)-1H-indazol-5-amine (0.060 g, 0.233 mmol, 95% yield). MS (ESI) m / z: 258.1 [M+1] + 4-((6- cyclopropyl -1-( tetrahydro -2H- pyran -4- yl )-1H- indazole -5- yl ) amino )-2-(2,6- bis(oxypiperidine) -3- yl ) isoindoline -1,3- dione. To a solution of 6-cyclopropyl-1-(tetrahydro-2H-pyran-4-yl)-1H-indazol-5-amine (0.060 g, 0.23 mmol) and 4-bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (0.083 g, 0.24 mmol) in dioxane (2 mL) was added chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) (0.018 g, 0.02 mmol) and potassium carbonate (0.097 mg, 0.70 mmol). The resulting mixture was stirred under nitrogen at 110 °C for 12 h. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by preparative HPLC to give 4-((6-cyclopropyl-1-(tetrahydro-2H-pyran-4-yl)-1H-indazol-5-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (26 mg, 0.051 mmol, 22% yield). 1 H NMR (400 MHz, DMSO-d6) δ 11.13 (s, 1H), 8.40 (s, 1H), 8.02 (s, 1H), 7.73 (s, 1H), 7.56 (dd, J = 7.2, 8.4 Hz, 1H), 7.51 (s, 1H), 7.18 (d, J = 7.2 Hz, 1H), 7.09 (d, J = 8.4 Hz, 1H), 5.14 (dd, J = 5.6, 12.8 Hz, 1H), 4.98 - 4.91 (m, 1H), 4.01 (dd, J = 3.6, 11.2 Hz, 2H), 3.58 (t, J = 11.6 Hz, 2H), 2.96 - 2.86 (m, 1H), 2.64 - 2.55 (m, 2H), 2.13 - 2.06 (m, 3H), 2.01 - 1.96 (m, 1H), 1.87 (dd, J = 2.0, 12.8 Hz, 2H), 0.95 - 0.92 (m, 2H), 0.82 - 0.79 (m, 2H); MS (ESI) m / z: 514.3 [M+1] + 。 Example 20 : 4-((1,3- Dimethyl -6-(2- methylpyridine -4- yl )-1H- indazole -5- yl ) amino )-2-(2,6- bis(oxo)piperidine -3- yl ) isoindoline -1,3- dione 6- bromo -1,3- dimethyl -5- nitro -1H- indazole. To a solution of 6-bromo-3-methyl-5-nitro-1H-indazole (1.30 g, 5.08 mmol) in tetrahydrofuran (15 mL) and N,N-dimethylformamide (15 mL) at 0 °C was added sodium hydride (0.146 g, 6.09 mmol). The mixture was stirred at 0 °C for 0.5 h. Iodomethane (1.08 g, 7.62 mmol) was added and the resulting mixture was stirred at 25 °C for 12 h. The reaction mixture was quenched with 60 mL of saturated aqueous ammonium chloride. The resulting solution was extracted with ethyl acetate (30 mL × 3). The combined organic phases were washed with brine (50 mL × 2), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The resulting residue was purified by preparative HPLC to give 6-bromo-1,3-dimethyl-5-nitro-1H-indazole (0.300 g, 1.11 mmol, 22% yield). MS (ESI) m / z: 271.9[M+1]+ 1,3- dimethyl -6-(2- methyl -4- pyridyl )-5- nitro - indazole. To a solution of 6-bromo-1,3-dimethyl-5-nitro-1H-indazole (0.190 g, 0.80 mmol) in dichloromethane (3 mL) was added 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.295 g, 1.10 mmol). The reaction mixture was stirred at 110 °C for 12 h. The reaction mixture was filtered and concentrated in vacuo. The resulting material was purified by silica gel column chromatography (5-15% ethyl acetate / petroleum ether) to give 1,3-dimethyl-6-(2-methyl-4-pyridyl)-5-nitro-indazole (0.080 g, 0.28 mmol, 32% yield). MS (ESI) m / z: 283.1 [M+1] + 1,3- dimethyl -6-(2- methylpyridine -4- yl )-1H- indazole -5- amine. To a solution of 1,3-dimethyl-6-(2-methyl-4-pyridyl)-5-nitro-indazole (0.080 g, 0.28 mmol) in ethanol (0.6 mL) was added ammonium chloride (0.153 g, 2.83 mmol) and iron powder (0.079 g, 1.42 mmol). The reaction mixture was stirred at 80 °C for 12 h. The reaction mixture was filtered and the filtrate was concentrated to give 1,3-dimethyl-6-(2-methylpyridin-4-yl)-1H-indazol-5-amine (0.050 g, 0.20 mmol, 69% yield). MS (ESI) m / z: 253.1 [M+1] + 3-((1,3- dimethyl -6-(2- methylpyridine -4- yl )-1H- indazole -5- yl ) amino ) Dimethyl phthalate. To a solution of 1,3-dimethyl-6-(2-methylpyridin-4-yl)-1H-indazol-5-amine (0.040 g, 0.16 mmol) in 1,4-dioxane (0.60 mL) was added dimethyl 3-bromophthalate (0.043 g, 0.16 mmol), potassium carbonate (0.061 g, 0.44 mmol), and bis(2-dicyclohexylphosphino-2,6-diisopropoxybiphenyl)(2-amino-1,1'-biphenyl-2-yl)palladium(II) (0.013 g, 0.02 mmol). The reaction mixture was stirred at 110 °C for 12 hours. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by preparative HPLC to give dimethyl 3-((1,3-dimethyl-6-(2-methylpyridin-4-yl)-1H-indazol-5-yl)amino)phthalate (0.05 g, 0.11 mmol, 70% yield). 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.66 (d, J = 6.0 Hz, 1H), 7.97 - 7.91 (m, 2H), 7.89 - 7.84 (m, 2H), 7.75 - 7.70 (m, 1H), 7.15 (t, J= 8.0 Hz, 1H), 6.94 (d, J= 7.2 Hz, 1H), 6.55 (d, J= 8.4 Hz, 1H), 4.03 (s, 3H), 3.76 (s, 3H), 3.74 (s, 3H), 2.61 (s, 3H), 2.52 - 2.51 (m, 3H); MS (ESI) m / z: 445.2[M+1] + 。 4-((1,3- dimethyl -6-(2- methylpyridine -4- yl )-1H- indazole -5- yl ) amino )-2-(2,6- 2,6-dioxopiperidin-3-yl -3- yl ) isoindoline -1,3- dione. To a solution of dimethyl 3-((1,3-dimethyl-6-(2-methylpyridin-4-yl)-1H-indazol-5-yl)amino)phthalate (0.05 g, 0.11 mmol) in pyridine (1 mL) was added 3-aminopiperidine-2,6-dione (0.021 g, 0.17 mmol) and lithium iodide (0.030 g, 0.22 mmol). The reaction mixture was stirred at 130 °C for 12 h. The reaction mixture was filtered and the filtrate was concentrated. The residue was purified by preparative HPLC to give 4-((1,3-dimethyl-6-(2-methylpyridin-4-yl)-1H-indazol-5-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (21 mg, 0.04 mmol, 37% yield). 1 H NMR (400 MHz, DMSO-d 6 ) δ 11.13 (s, 1H), 8.60 (d, J = 5.6 Hz, 1H), 8.43 (s, 1H), 7.88 (d, J = 1.6 Hz, 3H), 7.76 (d, J = 3.6 Hz, 1H), 7.39 (dd, J = 7.2, 8.4 Hz, 1H), 7.06 (d, J = 7.2 Hz, 1H), 6.64 (d, J = 8.4 Hz, 1H), 5.09 (dd, J = 5.6, 12.8 Hz, 1H), 4.05 (s, 3H), 2.96 - 2.84 (m, 1H), 2.63 (d, J = 2.4 Hz, 1H), 2.57 (s, 3H), 2.52 (s, 3H), 2.47 - 2.44 (m, 1H), 2.08 - 2.01 (m, 1H); MS (ESI) m / z: 509.2[M+1] + . Example 21 : 4 - ((6 - (2 - difluoromethyl ) pyridine - 4 - - yl ) - 1 - ( tetrahydro - 2H - pyran - 4 - - yl ) - 1H - indazole - 5 - - yl ) amino ) - 2 - (2,6 - bis(oxo)piperidine - 3 - - yl ) isoindoline - 1,3 - dione 2 - ( difluoromethyl ) - 4 - (4,4,5,5 - tetramethyl - 1,3,2 - dioxaborolane - 2 - - yl ) pyridine. To a solution of 4-bromo-2-(difluoromethyl)pyridine (0.530 g, 2.55 mmol) in 1,4-dioxane (5 mL) was added 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane) (0.776 g, 3.06 mmol), potassium acetate (0.749 g, 7.64 mmol), and dichloro(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) (0.208 g, 0.25 mmol). The suspension was degassed under vacuum and purged with nitrogen several times. The mixture was stirred at 100 °C for 12 h. The reaction was diluted with water (60 mL) and extracted with ethyl acetate (30 mL × 3). The combined organic phases were washed with brine (50 mL × 2), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The resulting crude material was purified by silica gel column chromatography (5-15% ethyl acetate / petroleum ether) to give 2-(difluoromethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.600 g, 2.3 mmol, 92% yield). 1 1H NMR (400 MHz, DMSO- δ 6 ) δ 8.75 (d, J = 4.8 Hz, 1H), 7.94 (s, 1H), 7.82 (s, 1H), 7.78 - 7.73 (m, 1H), 1.34 (s, 12H). 6-(2-( difluoromethyl ) pyridinyl -4- yl )-5- nitro -1-( tetrahydro -2H- pyran -4- yl )-1H- indazole. To a solution of 2-(difluoromethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.120 g, 0.47 mmol) in 1,4-dioxane (5 mL) and water (0.50 mL) was added 6-bromo-5-nitro-1-(tetrahydro-2H-pyran-4-yl)-1H-indazole (0.122 g, 0.38 mmol), potassium carbonate (0.129 g, 0.94 mmol), and dichloro(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) (0.038 g, 0.05 mmol). The suspension was degassed and purged with nitrogen several times. The mixture was stirred at 110 °C for 12 hours. The reaction mixture was filtered and the filtrate was concentrated and purified by preparative HPLC to give 6-(2-(difluoromethyl)pyridin-4-yl)-5-nitro-1-(tetrahydro-2H-pyran-4-yl)-1H-indazole (0.140 g, 0.37 mmol, 79% yield). 1 H NMR (400 MHz, DMSO- d 6 ) δ 8.79 (s, 1H), 8.77 (d, J= 5.2 Hz, 1H), 8.47 (s, 1H), 8.07 (s, 1H), 7.80 (s, 1H), 7.65 (d, J= 4.4 Hz, 1H), 5.17 - 5.04 (m, 1H), 4.01 (dd, J= 3.2, 11.6 Hz, 2H), 3.58 - 3.54 (m, 2H), 2.17 - 2.09 (m, 2H), 1.92 ( dd, J= 2.4, 12.0 Hz, 2H); MS (ESI) m / z: 375.1[M] + 。 6-(2-( difluoromethyl ) pyridine -4- yl )-1-( tetrahydro -2H- pyran -4- yl )-1H- Indazole -5- -amine. To a solution of 6-(2-(difluoromethyl)pyridin-4-yl)-5-nitro-1-(tetrahydro-2H-pyran-4-yl)-1H-indazole (0.140 g, 0.37 mmol) in ethanol (6 mL) was added ammonium chloride (0.202 g, 3.74 mmol) and iron powder (0.104 g, 1.87 mmol). The reaction mixture was stirred at 80 °C for 12 h. The reaction mixture was filtered and the filtrate was concentrated to give 6-(2-(difluoromethyl)pyridin-4-yl)-1-(tetrahydro-2H-pyran-4-yl)-1H-indazol-5-amine (0.110 g, 0.32 mmol, 85% yield). 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.75 (d, J= 5.2 Hz, 1H), 7.85 (s, 1H), 7.84 (s, 1H), 7.76 (d, J= 5.2 Hz, 1H), 7.57 (s, 1H), 7.04 (s, 1H), 5.76 (s, 1H), 4.86 - 4.78 (m, 1H), 3.98 (dd, J= 3.6, 11.2 Hz, 2H), 3.57 - 3.48 (m, 2H), 2.12 -2.02 (m, 2H), 1.86 (dd, J= 2.4, 12.4 Hz, 2H); MS (ESI) m / z: 345.1[M+1] + . 4-((6-(2-( difluoromethyl ) pyridine -4- -yl )-1-( tetrahydro -2H- pyran -4- -yl )-1H- indazole -5- [radical] 基 [radical] ) [radical] 胺基 [radical] )-2-(2,6- [radical] 二側氧基哌啶 [radical] -3- [radical] 基 [radical] ) [radical] 異吲哚啉 [radical] -1,3- [radical] 二酮。 [radical] To a solution of 6-(2-(difluoromethyl)pyridin-4-yl)-1-(tetrahydro-2H-pyran-4-yl)-1H-indazole-5-amine (0.080 g, 0.23 mmol) and 4-bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (0.082 g, 0.24 mmol) in 1,4-dioxane (3.5 mL) was added chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) (0.018 g, 0.02 mmol) and potassium carbonate (0.096 g, 0.70 mmol). The resulting mixture was stirred under nitrogen at 110 °C for 12 hours. The reaction mixture was filtered and the filtrate was concentrated and purified by preparative HPLC to give 4-((6-(2-(difluoromethyl)pyridin-4-yl)-1-(tetrahydro-2H-pyran-4-yl)-1H-indazol-5-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (46 mg, 0.07 mmol, 32% yield). [radical] 1 [radical] 1 HNMR (400 MHz, DMSO- [radical] d 6 [radical] 6 ) δ 11.12 (s, 1H), 8.63 (d, [radical] J= 5.2 Hz, 1H), 8.40 (s, 1H), 8.20 (s, 1H), 8.05 (s, 1H), 7.90 (s, 1H), 7.84 (s, 1H), 7.73 (d, [radical] J= 5.2 Hz, 1H), 7.41 - 7.34 (m, 1H), 7.07 - 6.75 (m, 2H), 6.71 (d, [radical] J = 8.4 Hz, 1H), 5.12 - 5.01 (m, 2H), 4.07 - 4.00 (m, 2H), 3.60 - 3.54 (m, 2H), 2.96 - 2.84 (m, 1H), 2.65 - 2.55 (m, 2H), 2.20 - 2.12 (m, 2H), 2.06 - 1.99 (m, 1H), 2.02 - 1.95 (m, 2H); MS (ESI) m / z: 601.2[M+1] + 。 Example 22 : 4-((3-( dimethylamino )-2,3- dihydro -1H- indene -5- yl ) amino )-2-((S)-3- methyl -2,6- bis(oxo)piperidine -3- yl ) isoindoline -1,3- dione (E)-6- bromo -2,3- dihydro -1H- indene -1- ketoxime 。 To a solution of 6-bromoindan-1-one (5.0 g, 23.6 mmol) in ethanol (50 mL) was added hydroxylamine hydrochloride (3.2 g, 47.3 mmol) and pyridine (4.9 g, 61.9 mmol, 5 mL). The reaction mixture was stirred at 80 °C for 12 h. The reaction mixture was quenched with water (50 mL), and the aqueous layer was extracted with dichloromethane (3 × 50 mL). The combined organic extracts were washed with brine (50 mL), dried over sodium sulfate and filtered. The solvent was removed under reduced pressure to give 6-bromoindan-1-one oxime (4.5 g, 19.9 mmol, 84% yield). 1 H NMR (400MHz DMSO-d 6 ) δ 11.09 (s, 1H), 7.63 (brs, 1H), 7.49 (d, J= 8.0 Hz, 1H), 7.32 (d, J= 8.0 Hz, 1H), 2.95 - 2.80 (m, 2H), 2.79 - 2.77 (m, 2H); MS (ESI) m / z224.0 [M+1] + 6- bromo -2,3- dihydro -1H- indene -1- amine. To a solution of 6-bromoindan-1-one oxime (4.6 g, 20.35 mmol) in methanol (100 mL) was added trimethoxymolybdenum (3.51 g, 24.42 mmol) and sodium borohydride (3.85 g, 101.74 mmol). The reaction mixture was stirred at 25 °C for 12 h. The reaction mixture was quenched with 1N aqueous hydrochloric acid (200 ml) and ethyl acetate (200 ml). The aqueous solution was made basic and then extracted with dichloromethane (3 × 200 ML). The combined organic extracts were dried over sodium sulfate, filtered and concentrated under reduced pressure to give 6-bromoindan-1-amine (2.3 g, 10.8 mmol, 53%). MS (ESI) m / z195.0 [M-16] + 6- Bromine -N,N- Dimethyl -2,3- Dihydro -1H- Indene -1- Amine. To a solution of 6-bromoindan-1-amine (2.3 g, 10.8 mmol) in formic acid (4 mL) was added water containing formaldehyde (45.5 g, 500.9 mmol, 41.8 mL). The reaction mixture was stirred at 100 °C for 12 h. The aqueous solution was made alkaline and then extracted with dichloromethane (3 × 100 mL) and dried over sodium sulfate. The extract was then filtered and concentrated under reduced pressure to give 6-bromo-N,N-dimethyl-indan-1-amine (1.1 g, 4.58 mmol, 42%). 1 H NMR (400MHz CDCl 3 ) δ 7.49 (s, 1H), 7.32 (d, J= 8.0 Hz, 1H), 7.08 (d, J= 8.0 Hz, 1H), 4.30 (t, J= 6.8 Hz, 1H), 2.90 - 2.86 (m, 1H), 2.80 - 2.76 (m, 1H), 2.25 (s, 6H), 2.08 - 2.04 (m, 2H); MS (ESI) m / z240.0, 242.0 [M+1] + 4-((3-( Dimethylamino )-2,3- Dihydro -1H- Indene -5- yl ) Amino )-2-((S)-3- Methyl -2,6- bis(oxypiperidine) -3- radical ) isoindoline -1,3- dione. To a solution of (S)-4-amino-2-(3-methyl-2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (0.100 g, 0.35 mmol) in 1,4-dioxane (3 mL) was added potassium carbonate (0.120 g, 0.87 mmol), [2-(2-aminophenyl)phenyl]-chloro-palladium; dicyclohexyl-[3-(2,4,6-triisopropylphenyl)phenyl]phosphane (0.030 g, 0.04 mmol) and 6-bromo-N,N-dimethyl-2,3-dihydro-1H-inden-1-amine (0.100 g, 0.42 mmol). The resulting mixture was stirred at 100 °C for 12 h under nitrogen. The mixture was diluted with dichloromethane (20 mL) and acetonitrile (20 mL) and filtered. The filtrate was concentrated under reduced pressure. The resulting residue was dissolved in N,N-dimethylformamide (4 mL) and filtered. The filtrate was purified by preparative HPLC to give 4-((3-(dimethylamino)-2,3-dihydro-1H-inden-5-yl)amino)-2-((S)-3-methyl-2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (40 mg, 0.802 mmol, 23% yield). 1 H NMR (400MHz DMSO-d 6 ) δ 11.02 (s, 2H), 8.52 (s, 1H), 7.72 (s, 1H), 7.61 (d, J= 7.2 Hz, 1H), 7.59 (d, J= 7.2 Hz, 1H), 7.49 - 7.35 (m, 2H), 7.19 (d, J= 6.8 Hz, 1H), 4.95 - 4.94 (m, 1H), 3.11 - 3.02 (m, 1H), 2.92 - 2.85 (m, 1H), 2.73 (d, J= 4.8 Hz, 3H), 2.69 - 2.56 (m, 3H), 2.54 (d, J = 5.2 Hz, 3H), 2.42 - 2.33 (m, 2H), 2.09 - 2.03 (m, 1H), 1.91 (s, 3H); MS (ESI) m / z447.1 [M+1] + 。 Example 23 : (S)-2-(2,6- bis(oxo)piperidine -3- yl )-4-((1- methyl -6-(2- methylpyridine -4- yl )-1H- indazole -5- yl ) amino ) isoindoline -1,3- dione and (R)-2-(2,6- bis(oxo)piperidine -3- yl )-4-((1- methyl -6-(2- methylpyridine -4- yl )-1H- indazole -5- yl ) amino ) isoindoline -1,3- dione 6- bromo -1- methyl -5- nitro -1H- indazole. To a 500 mL three-necked flask was added 4-bromo-2-fluoro-5-nitrobenzaldehyde (10.00 g, 40.32 mmol), potassium carbonate (8.400 g, 60.87 mmol), isopropanol (80 mL), and water (40 mL). The mixture was stirred at 41 °C for 1 hour, and methylhydrazine (11.730 g, 101.85 mmol) was added dropwise. The resulting mixture was heated to 77 °C and stirred for 6 hours. The mixture was cooled to 20 °C and water (150 mL) was added. The mixture was stirred for 1 hour and filtered. The separated solid was washed with water (20 mL × 3) and dried under reduced pressure to give 6-bromo-1-methyl-5-nitro-1H-indazole (7.00 g, 27.34 mmol, 67.8% yield). 1 1H NMR (400 MHz, CDCl3) δ 8.38 (s, 1H), 8.13 (s, 1H), 7.77 (s, 1H), 4.12 (s, 3H). 1- methyl -6-(2- methylpyridine -4- yl )-5- nitro -1H- indazole. To a solution of 6-bromo-1-methyl-5-nitro-1H-indazole (2.0 g, 7.81 mmol) and 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (1.80 g, 8.22 mmol) in dioxane (30 mL) was added cesium carbonate (7.62 g, 23.43 mmol) and dichloro(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) (0.319 g, 0.39 mmol). The resulting mixture was stirred under nitrogen at 110 °C for 12 hours. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give 1-methyl-6-(2-methylpyridin-4-yl)-5-nitro-1H-indazole (1.500 g, 5.59 mmol, 71.6% yield). 11H NMR (400 MHz, CDCl3) δ 8.57 (d, J = 5.2 Hz, 1H), 8.53 (s, 1H), 8.22 (s, 1H), 7.33 (s, 1H), 7.18 (s, 1H), 7.12 (d, J = 4.8 Hz, 1H), 4.15 (s, 3H), 2.64 (s, 3H); MS (ESI) m / z: 269.3[M+1] + 。 1- methyl -6-(2- methylpyridinyl -4- yl )-1H- indazole -5- amine. To a solution of 1-methyl-6-(2-methylpyridin-4-yl)-5-nitro-1H-indazole (1.50 g, 5.59 mmol) in ethanol (15 mL) and water (5 mL) was added ammonium chloride (1.51 g, 27.96 mmol) and iron powder (1.56 g, 27.96 mmol). The resulting mixture was stirred at 70 °C for 12 h. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The resulting residue was extracted with water (50 mL) and ethyl acetate (3 × 60 mL). The combined organic phases were dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to give 1-methyl-6-(2-methylpyridin-4-yl)-1H-indazol-5-amine (1.3 g, 5.46 mmol, 97.6% yield). MS (ESI) m / z: 239.1[M+1]+ 1 1H NMR (400 MHz, CDCl3) δ 8.60 (d, J = 4.8 Hz, 1H), 7.81 (s, 1H), 7.35 (s, 1H), 7.30 (d, J = 5.2 Hz, 1H), 7.16 (s, 1H), 7.04 (s, 1H), 4.03 (s, 3H), 2.65 (s, 3H). 2-(2,6- bis(oxo)piperidinyl -3- yl )-4-((1- methyl -6-(2- methylpyridine -4- yl )-1H- indazole -5- yl ) amino ) isoindoline -1,3- dione. To a solution of 1-methyl-6-(2-methylpyridin-4-yl)-1H-indazole-5-amine (1.300 g, 5.46 mmol) and 4-bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (1.931 g, 5.73 mmol) in dioxane (30 mL) was added potassium carbonate (2.258 g, 16.36 mmol) and chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) (0.215 g, 0.27 mmol). The resulting mixture was stirred under nitrogen at 110 °C for 12 hours. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by reverse-phase preparative HPLC (5-35% acetonitrile / water, 0.1% 2,2,2-trifluoroacetic acid modifier). The isolated material was lyophilized to give the crude 2-(2,6-dioxopiperidin-3-yl)-4-((1-methyl-6-(2-methylpyridin-4-yl)-1H-indazol-5-yl)amino)isoindoline-1,3-dione (1.80 g, 3.64 mmol, 66.7% yield). MS (ESI) m / z: 495.2 [M+1]+ ( S)-2-(2,6- dioxopiperidine -3- yl )-4-((1- methyl -6-(2- methylpyridine -4- yl )-1H- indazole -5- yl ) Amino ) Isoindoline -1,3- Dione. 2-(2,6-Dioxopiperidin-3-yl)-4-((1-methyl-6-(2-methylpyridin-4-yl)-1H-indazol-5-yl)amino)isoindoline-1,3-dione (0.600 g, 1.21 mmol) was purified by chiral preparative SFC (70% ethanol / acetonitrile). The separated material was concentrated under reduced pressure to give ( (S)-2-(2,6-Dioxopiperidin-3-yl)-4-((1-methyl-6-(2-methylpyridin-4-yl)-1H-indazol-5-yl)amino)isoindoline-1,3-dione (210 mg, 0.421 mmol, 34.7% yield). 1 H NMR (400 MHz, DMSO-d6) δ 11.14 (s, 1H), 8.38 (d, J = 5.2 Hz, 1H), 8.34 (s, 1H), 8.13 (d, J = 0.8 Hz, 1H), 7.87 (s, 1H), 7.84 (s, 1H), 7.43 (s, 1H), 7.40 (dd, J = 7.2, 8.4 Hz, 1H), 7.33 (d, J = 4.4 Hz, 1H), 7.06 (d, J = 6.8 Hz, 1H), 6.75 (d, J = 8.8 Hz, 1H), 5.08 (dd, J = 5.6, 12.8 Hz, 1H), 4.12 (s, 3H), 2.94 - 2.85 (m, 1H), 2.63 - 2.58 (m, 2H), 2.43 (s, 3H), 2.06 - 2.01 (m, 1H); MS (ESI) m / z: 495.3 [M+1]+ (R)-2-(2,6- Dioxopiperidine -3- yl )-4-((1- methyl -6-(2- methylpyridine -4- yl )-1H- Indazole -5- radical ) amino group ) isoindoline -1,3- dione. 2-(2,6-Dioxopiperidin-3-yl)-4-((1-methyl-6-(2-methylpyridin-4-yl)-1H-indazol-5-yl)amino)isoindoline-1,3-dione (0.600 g, 1.21 mmol) was purified by chiral preparative SFC (70% ethanol / acetonitrile). The separated material was concentrated under reduced pressure to give ( (R)-2-(2,6-Dioxopiperidin-3-yl)-4-((1-methyl-6-(2-methylpyridin-4-yl)-1H-indazol-5-yl)amino)isoindoline-1,3-dione (220 mg, 0.441 mmol, 36.3% yield). 1 H NMR (400 MHz, DMSO-d6) δ 11.12 (s, 1H), 8.38 (d, J = 4.8 Hz, 1H), 8.32 (s, 1H), 8.13 (d, J = 0.8 Hz, 1H), 7.88 (s, 1H), 7.84 (s, 1H), 7.42 - 7.39 (m, 2H), 7.32 (dd, J = 1.6, 5.2 Hz, 1H), 7.06 (d, J = 7.2 Hz, 1H), 6.77 (d, J = 8.8 Hz, 1H), 5.08 (dd, J = 5.2, 12.8 Hz, 1H), 4.12 (s, 3H), 2.95 - 2.86 (m, 1H), 2.63 - 2.55 (m, 2H), 2.43 (s, 3H), 2.07 - 2.02 (m, 1H); MS (ESI) m / z: 495.1 [M+1]+. Example 24 : (R)-4-((1,3- dimethyl -6-(2- methylpyridine -4- radical )-2- Side oxy group -2,3- Dihydro -1H- Benzo [d] Imidazole -5- Group ) Amino group )-2-(2,6- Dioxide piperidine -3- Group ) Isoindoline -1,3- Dione and (S)-4-((1,3- Dimethyl -6-(2- Methylpyridine -4- Group )-2- Side oxy group -2,3- Dihydro -1H- Benzo [d] Imidazole -5- Group ) Amino group )-2-(2,6- Dioxide piperidine -3- Group ) Isoindoline -1,3- Dione 5- Bromine -1,3- Dimethyl - Benzimidazole -2- Ketone. At 0 °C, sodium hydride (1.590 g, 66.06 mmol) was added to a solution of 6-bromo-1-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one (5.00 g, 22.02 mmol) in N,N-dimethylformamide (100 mL), and the mixture was stirred at 0 °C for 0.5 h. Iodomethane (15.63 g, 110.10 mmol) was added. The resulting mixture was stirred at 25 °C for 12 h. The reaction mixture was quenched with 60 mL of saturated aqueous ammonium chloride and extracted with ethyl acetate (100 mL × 3). The combined organic phases were washed with brine (150 mL × 2), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give 5-bromo-1,3-dimethyl-benzoimidazol-2-one (5.00 g, 20.74 mmol, 94.2% yield). MS (ESI) m / z: 241.1 [M] 5- bromo -1,3- dimethyl -6- nitro -1,3- dihydro -2H- benzo [d] imidazole -2- one Under nitrogen, fuming nitric acid (1.85 mL, 41.48 mmol) was slowly added to a solution of 5-bromo-1,3-dimethyl-1,3-dihydro-2H-benzo[d]imidazol-2-one (5.00 g, 20.74 mmol) in acetic anhydride (83 mL) at -30 °C, ensuring that the temperature remained below -25 °C. The mixture was slowly warmed to 0 °C and stirred for 1 h. The reaction mixture was quenched with water (300 mL). The resulting solution was extracted with ethyl acetate (300 mL × 3). The combined organic phases were washed with brine (300 mL × 2), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give 5-bromo-1,3-dimethyl-6-nitro-1,3-dihydro-2H-benzo[d]imidazol-2-one (4.50 g, 15.73 mmol, 75.8% yield). 1H NMR (400 MHz, DMSO-d6) δ 7.97 (s, 1H), 7.70 (s, 1H), 3.37 (s, 6H); MS (ESI) m / z: 287.9 [M+2]+. 1,3- Dimethyl -5-(2- Methylpyridine -4- yl )-6- Nitro -1,3- Dihydro -2H- Benzene并 [d] Imidazole -2- Ketone. To a solution of 5-bromo-1,3-dimethyl-6-nitro-1,3-dihydro-2H-benzo[d]imidazol-2-one (4.00 g, 13.98 mmol) in 1,4-dioxane (40 mL) was added 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (4.60 g, 20.97 mmol), cesium carbonate (13.63 g, 41.95 mmol) and dichloro(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) (1.140 g, 1.39 mmol). The suspension was degassed and purged with nitrogen. The mixture was stirred at 110 °C for 12 h. The reaction mixture was quenched with water (300 mL) and extracted with ethyl acetate (300 mL × 3). The combined organic phases were washed with brine (300 mL × 2), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The resulting residue was purified by silica gel column chromatography (5-15% methanol / dichloromethane) to give 1,3-dimethyl-5-(2-methylpyridin-4-yl)-6-nitro-1,3-dihydro-2H-benzo[d]imidazol-2-one (4.00 g, 13.41 mmol, 95.9% yield). 1H NMR (400 MHz, DMSO-d6) δ 8.48 (d, J = 4.8 Hz, 1H), 8.01 (s, 1H), 7.32 (s, 1H), 7.26 (s, 1H), 7.14 (dd, J = 1.2, 4.8 Hz, 1H), 3.43 (s, 3H), 3.39 (s, 3H), 2.52 (s, 3H); MS (ESI) m / z: 299.1[M+1]+. 5- Amino -1,3- Dimethyl -6-(2- Methylpyridine -4- yl )-1,3- dihydro -2H- benzo [d] imidazole -2- one. To a solution of 1,3-dimethyl-5-(2-methylpyridin-4-yl)-6-nitro-1,3-dihydro-2H-benzo[d]imidazol-2-one (4.00 g, 13 mmol) in ethanol (60 mL) and water (20 mL) was added ammonium chloride (7.24 g, 134 mmol) and iron powder (3.74 g, 67 mmol). The reaction mixture was stirred at 80 °C for 12 h. The reaction mixture was filtered and the filtrate was concentrated in vacuo to give 5-amino-1,3-dimethyl-6-(2-methylpyridin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (2.600 g, 9.69 mmol, 72.3% yield). MS (ESI) m / z: 269.0 [M+1]+. 4-((1,3- dimethyl -6-(2- methylpyridine -4- yl )-2- cyano -2,3- dihydro -1H- benzo [d] imidazole -5- yl ) amino )-2-(2,6- dicyanopiperidine -3- yl ) isoindoline -1,3- dione. To a solution of 5-amino-1,3-dimethyl-6-(2-methylpyridin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (2.60 g, 9.69 mmol) in 1,4-dioxane (50 mL) was added 4-bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (3.43 g, 10.17 mmol), potassium carbonate (4.01 g, 29.07 mmol), and chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) (0.380 g, 0.48 mmol). The resulting suspension was degassed and purged with nitrogen. The mixture was stirred at 115 °C for 12 h. The reaction was filtered and the filtrate was concentrated under reduced pressure. The resulting material was purified by semi-preparative reverse-phase HPLC (15-45% acetonitrile / water, 0.1% trifluoroacetic acid modifier). The relevant eluate was lyophilized to give 4-((1,3-dimethyl-6-(2-methylpyridin-4-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (2.1 g, 3.82 mmol, 39% yield). 1H NMR (400 MHz, DMSO-d6) δ 11.12 (s, 1H), 8.65 (d, J = 6.0 Hz, 1H), 8.48 (s, 1H), 7.98 (s, 1H), 7.88 (d, J = 5.4 Hz, 1H), 7.49 (s, 1H), 7.43 (t, J = 8.0 Hz, 1H), 7.38 (s, 1H), 7.11 (d, J = 7.2 Hz, 1H), 6.74 - 6.69 (m, 1H), 5.09 (dd, J = 5.4, 12.8 Hz, 1H), 3.42 (s, 3H), 3.37 (s, 3H), 2.96 - 2.84 (m, 1H), 2.62 (s, 3H), 2.60 - 2.54 (m, 1H), 2.53 - 2.51 (m, 1H), 2.09 - 2.01 (m, 1H); MS (ESI) m / z: 525.2[M+1]+。 (S)-4-((1,3- dimethyl -6-(2- methylpyridine -4- yl )-2- Side oxy group -2,3- Dihydro -1H- Benzo [d] Imidazole -5- Group ) Amino group )-2-(2,6- Di-side oxy piperidine -3- Group ) Isoindoline -1,3- Dione. 4-((1,3-Dimethyl-6-(2-methylpyridin-4-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (1.00 g, 1.91 mmol) was separated by chiral preparative SFC (70 - 70% isopropanol / acetonitrile). The peak 1 was concentrated under reduced pressure and extracted with sodium bicarbonate (50 mL × 2) and dichloromethane (60 mL × 3). The combined organic layers were washed with water (50 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure. The resulting residue was treated with acetonitrile (6 mL) and water (60 mL) and lyophilized to obtain (S)-4-((1,3-dimethyl-6-(2-methylpyridin-4-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (359 mg, 0.684 mmol, 35% yield). 1H NMR (400 MHz, DMSO-d6) δ 11.12 (s, 1H), 8.34 (d, J = 5.2 Hz, 1H), 8.27 (s, 1H), 7.45 - 7.39 (m, 1H), 7.35 (s, 1H), 7.32 (d, J = 1.2 Hz, 2H), 7.25 (d, J = 5.2 Hz, 1H), 7.07 (d, J = 7.2 Hz, 1H), 6.78 (d, J = 8.4 Hz, 1H), 5.08 (dd, J = 5.2, 12.8 Hz, 1H), 3.39 (s, 3H), 3.36 (s, 3H), 2.95 - 2.83 (m, 1H), 2.62 - 2.53 (m, 1H), 2.52 - 2.50 (m, 1H), 2.40 (s, 3H), 2.09 - 2.00 (m, 1H); MS (ESI) m / z: 525.3[M+1]+. (R)-4-((1,3- Dimethyl -6-(2- Methylpyridine -4- yl )-2- Oxo -2,3- Dihydro -1H- Benzo [d] Imidazole -5- yl ) Amino )-2-(2,6- Bis(oxo)piperidine -3- yl ) Isoindoline -1,3- Dione. 4-((1,3-Dimethyl-6-(2-methylpyridin-4-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (1.00 g, 1.91 mmol) was separated by chiral preparative SFC (70 - 70% isopropanol / acetonitrile). The peak 2 was concentrated under reduced pressure and extracted with sodium bicarbonate (50 mL × 2) and dichloromethane (60 mL × 3). The combined organic layers were washed with water (50 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure. The resulting residue was treated with acetonitrile (6 mL) and water (60 mL) and lyophilized to give (R)-4-((1,3-dimethyl-6-(2-methylpyridin-4-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (359 mg, 0.684 mmol, 35% yield). 1H NMR (400 MHz, DMSO-d6) δ 11.11 (s, 1H), 8.35 (d, J = 5.2 Hz, 1H), 8.27 (s, 1H), 7.42 (dd, J = 7.2, 8.4 Hz, 1H), 7.36 (s, 1H), 7.32 (s, 1H), 7.31 (s, 1H), 7.28 - 7.25 (m, 1H), 7.07 (d, J = 7.2 Hz, 1H), 6.78 (d, J = 8.4 Hz, 1H), 5.08 (dd, J = 5.2, 12.8 Hz, 1H), 3.39 (s, 3H), 3.36 (s, 3H), 2.95 - 2.83 (m, 1H), 2.64 - 2.56 (m, 1H), 2.56 - 2.52 (m, 1H), 2.41 (s, 3H), 2.08 - 2.01 (m, 1H); MS (ESI) m / z: 525.3[M+1]+。 Example 25 : (R)-4-((6-(2,6- Dimethylpyridine -4- yl )-1,3- Dimethyl -2- Oxo -2,3- dihydro -1H- benzo [d] imidazole -5- yl ) amino )-2-(2,6- bis(oxypiperidine) -3- yl ) isoindoline -1,3- dione and (S)-4-((6-(2,6- dimethylpyridine -4- yl )-1,3- dimethyl -2- oxo -2,3- dihydro -1H- benzo [d] imidazole -5- yl ) amino )-2-(2,6- bis(oxypiperidine) -3- yl ) isoindoline -1,3- dione 5-(2,6- dimethylpyridine -4- yl )-1,3- dimethyl -6- nitro -1,3- dihydro -2H- Benzo [d] Imidazole -2- One. To a solution of 5-bromo-1,3-dimethyl-6-nitro-1,3-dihydro-2H-benzo [d] imidazol-2-one (0.230 g, 0.80 mmol) in 1,4-dioxane (0.5 mL) was added 2,6-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine (0.281 g, 1.21 mmol), cesium carbonate (0.784 g, 2.41 mmol) and dichloro (1,1'-bis (diphenylphosphino) ferrocene) palladium (II) (0.066 g, 0.08 mmol). The suspension was degassed and purged with nitrogen. The mixture was stirred at 110 °C for 12 hours. The reaction mixture was concentrated in vacuo and the resulting residue was purified by silica gel column chromatography (5-15% methanol / dichloromethane) to give 5-(2,6-dimethylpyridin-4-yl)-1,3-dimethyl-6-nitro-1,3-dihydro-2H-benzo [d] imidazol-2-one (0.180 g, 0.58 mmol, 71% yield). 1 H NMR (400 MHz, DMSO- d 6 ) δ 7.99 (s, 1H), 7.30 (s, 1H), 7.02 (s, 2H), 3.43 (s, 3H), 3.39 (s, 3H), 2.46 (s, 6H); MS (ESI) m / z: 313.2 [M]. 5- Amino -6-(2,6- Dimethylpyridine -4- Group )-1,3- Dimethyl -1,3- Dihydro -2H- Benzo [d] Imidazole -2- One. To a solution of 5-(2,6-dimethylpyridin-4-yl)-1,3-dimethyl-6-nitro-1,3-dihydro-2H-benzo[d]imidazol-2-one (0.180 g, 0.58 mmol) in ethanol (3 mL) and water (1 mL) was added ammonium chloride (0.156 g, 2.88 mmol) and iron powder (0.322 g, 5.76 mmol). The reaction mixture was stirred at 80 °C for 12 h. The reaction mixture was filtered and the filtrate was concentrated to give 5-amino-6-(2,6-dimethylpyridin-4-yl)-1,3-dimethyl-1,3-dihydro-2H-benzo[d]imidazol-2-one (0.130 g, 0.46 mmol, 79% yield). MS (ESI) m / z: 283.1 [M+1] + 。 4-((6-(2,6- dimethylpyridine -4- yl )-1,3- dimethyl -2- side oxy -2,3- dihydro -1H- benzo [d] imidazole -5- yl ) amino )-2-(2,6- di side oxy piperidine -3- yl ) isoindoline -1,3- dione. To a solution of 5-amino-6-(2,6-dimethylpyridin-4-yl)-1,3-dimethyl-1,3-dihydro-2H-benzo[d]imidazol-2-one (0.130 g, 0.42 mmol) in 1,4-dioxane (3 mL) was added 4-bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (0.168 g, 0.500 mmol), potassium carbonate (0.172 g, 1.25 mmol), and chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) (0.033 g, 0.04 mmol). The suspension was degassed and purged with nitrogen. The mixture was stirred at 110 °C for 12 h. The reaction mixture was filtered and the filtrate was concentrated. The resulting residue was purified by semi-preparative reverse-phase HPLC (13-43% acetonitrile / water, 0.1% trifluoroacetic acid modifier). The collected eluent fractions were lyophilized to give 4-((6-(2,6-dimethylpyridin-4-yl)-1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (153 mg, 0.284 mmol, 68% yield). 1 H NMR (400 MHz, DMSO- d 6 ) δ 11.14 (s, 1H), 8.53 (s, 1H), 7.82 (s, 2H), 7.48 (s, 1H), 7.45 - 7.40 (m, 1H), 7.39 (s, 1H), 7.10 (d, J= 7.2 Hz, 1H), 6.71 - 6.67 (m, 1H), 5.10 (dd, J= 5.4, 12.8 Hz, 1H), 3.42 (s, 3H), 3.38 (s, 3H), 2.96 - 2.85 (m, 1H), 2.65 - 2.62 (m, 1H), 2.60-2.57 (m, 1H), 2.57 (s, 6H), 2.09 - 2.02 (m, 1H); MS (ESI) m / z: 539.2[M+1] + (R)-4-((6-(2,6- dimethylpyridine -4- group )-1,3- dimethyl -2- side oxy group -2,3- dihydro -1H- benzo [d] imidazole -5- group ) amino group )-2-(2,6- bis(side oxy)piperidine -3- group ) isoindoline -1,3- dione. 4-((6-(2,6-Dimethylpyridin-4-yl)-1,3-dimethyl-2-side oxy-2,3-dihydro-1H-benzo[d]imidazol-5-yl)amino)-2-(2,6-bis(side oxy)piperidin-3-yl)isoindoline-1,3-dione (0.120 g, 0.22 mmol) was separated by chiral preparative SFC (70 - 70% isopropanol / acetonitrile). After separation, one of the two separated peaks was concentrated under reduced pressure to give (R)-4-((6-(2,6-Dimethylpyridin-4-yl)-1,3-dimethyl-2-side oxy-2,3-dihydro-1H-benzo[d]imidazol-5-yl)amino)-2-(2,6-bis(side oxy)piperidin-3-yl)isoindoline-1,3-dione (42.74 mg, 0.079 mmol, 35.6% yield). 1 H NMR (400 MHz, DMSO- d 6 ) δ 11.11 (s, 1H), 8.28 (s, 1H), 7.47 - 7.39 (m, 1H), 7.31 (d, J = 1.6 Hz, 2H), 7.14 (s, 2H), 7.08 (d, J = 7.2 Hz, 1H), 6.81 (d, J = 8.4 Hz, 1H), 5.08 (dd, J = 5.4, 12.8 Hz, 1H), 3.39 (s, 3H), 3.37 (s, 3H), 2.96 - 2.84 (m, 1H), 2.65 - 2.60 (m, 1H), 2.58 - 2.53 (m, 1H), 2.35 (s, 6H), 2.07 - 1.99 (m, 1H); MS (ESI) m / z: 539.3[M+1] + 。 (S)-4-((6-(2,6- Dimethylpyridine -4- yl )-1,3- Dimethyl -2- Lateral oxy group -2,3- Dihydro -1H- Benzo [d] Imidazole -5- yl ) Amino )-2-(2,6- Dilateral oxy piperidine -3- yl ) Isoindoline -1,3- Dione. 4 - ((6 - (2,6 - Dimethylpyridin - 4 - yl)-1,3 - dimethyl - 2 - lateral oxy - 2,3 - dihydro - 1H - benzo[d]imidazol - 5 - yl)amino)-2-(2,6 - dilateral oxy piperidin - 3 - yl)isoindoline - 1,3 - dione (0.120 g, 0.22 mmol) was separated by chiral preparative SFC (70 - 70% isopropanol / acetonitrile). After separation, one of the two separated peaks was concentrated under reduced pressure to give (S)-4 - ((6 - (2,6 - Dimethylpyridin - 4 - yl)-1,3 - dimethyl - 2 - lateral oxy - 2,3 - dihydro - 1H - benzo[d]imidazol - 5 - yl)amino)-2-(2,6 - dilateral oxy piperidin - 3 - yl)isoindoline - 1,3 - dione (58 mg, 0.108 mmol, 48% yield). 1 H NMR (400 MHz, DMSO- d 6 ) δ 11.13 (s, 1H), 8.48 (s, 1H), 7.79 - 7.64 (m, 2H), 7.48 - 7.39 (m, 2H), 7.38 (s, 1H), 7.10 (d, J= 7.2 Hz, 1H), 6.75 - 6.69 (m, 1H), 5.13 - 5.07 (m, 1H), 3.41 (s, 3H), 3.38 (s, 3H), 2.98 - 2.84 (m, 1H), 2.65 - 2.61 (m, 1H), 2.60-2.56 (m, 1H), 2.54 (s, 6H), 2.09 - 2.00 (m, 1H); MS (ESI) m / z: 539.3[M+1] + 。 Example 26 : 2-((R)-2,6- bis(oxo)piperidine -3- yl )-4-((6-(2- methylpyridine -4- yl )-1-((R)- tetrahydrofuran -3- yl )-1H- indazole -5- yl ) amino ) isoindoline -1,3- dione and 2-((S)-2,6- bis(oxo)piperidine -3- yl )-4-((6-(2- methylpyridine -4- group )-1-((R)- tetrahydrofuran -3- group )-1H- indazole -5- group ) amino group ) isoindoline -1,3- dione (R)-6- bromo -5- nitro -1-( tetrahydrofuran -3- group )-1H- indazole. A mixture of 6-bromo-5-nitro-1H-indazole (5.00 g, 20.66 mmol), (S)-tetrahydrofuran-3-ol (2.18 g, 24.79 mmol) and triphenylphosphine (6.50 g, 24.78 mmol) was dried under vacuum for 30 minutes, and then tetrahydrofuran (30 mL) was added. A solution of (E)-di-tert-butyl diazene-1,2-dicarboxylate (5.70 g, 24.78 mmol) in tetrahydrofuran (20 mL) was added, and the mixture was stirred at 25 °C for 12 hours. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by reverse-phase preparative HPLC. The separated desired substance was lyophilized to give (R)-6-bromo-5-nitro-1-(tetrahydrofuran-3-yl)-1H-indazole (3.50 g, 11.21 mmol, 54% yield). 1 H NMR (400 MHz, CDCl 3) δ 8.38 (s, 1H), 8.16 (s, 1H), 7.89 (s, 1H), 5.31 - 5.25 (m, 1H), 4.31 - 4.26 (m, 1H), 4.20 - 4.19 (m, 2H), 4.05 - 3.99 (m, 1H), 2.60 - 2.52 (m, 1H), 2.50 - 2.42 (m, 1H); MS (ESI) m / z: 313.9 [M+1] + 。 (R)-6-(2- methylpyridine -4- -yl )-5- nitro -1-( tetrahydrofuran -3- -yl )-1H- indazole. To a solution of (R)-6-bromo-5-nitro-1-(tetrahydrofuran-3-yl)-1H-indazole (3.00 g, 9.61 mmol) and 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (2.53 g, 11.53 mmol) in dioxane (40 mL) was added potassium carbonate (3.90 g, 28.26 mmol) and dichloro(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloromethane adduct (0.393 g, 0.48 mmol). The resulting mixture was stirred under nitrogen at 110 °C for 12 h. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give (R)-6-(2-methylpyridin-4-yl)-5-nitro-1-(tetrahydrofuran-3-yl)-1H-indazole (3.00 g, 9.25 mmol, 96% yield). 1 H NMR (400 MHz, CDCl3) δ 8.57 (d, J= 5.2 Hz, 1H), 8.52 (s, 1H), 8.25 (s, 1H), 7.44 (s, 1H), 7.27 (s, 1H), 7.16 (s, 1H), 7.10 (dd, J = 5.2, 1.2 Hz, 1H), 5.35 - 5.30 (m, 1H), 4.31 - 4.25 (m, 1H), 4.20 (d, J = 5.2 Hz, 2H), 4.05 - 3.99 (m, 1H), 2.63 (s, 3H), 2.59 - 2.49 (m, 2H); MS (ESI) m / z: 325.1 [M+1] + 。 (R)-6-(2- methylpyridine -4- yl )-1-( tetrahydrofuran -3- yl )-1H- indazole -5- amine. To a solution of (R)-6-(2-methylpyridin-4-yl)-5-nitro-1-(tetrahydrofuran-3-yl)-1H-indazole (3.00 g, 9.25 mmol) in ethanol (30 mL) and water (10 mL) was added iron powder (2.58 g, 46.25 mmol) and ammonium chloride (4.99 g, 92.5 mmol). The resulting mixture was stirred at 70 °C for 2 h. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure to give the crude (R)-6-(2-methylpyridin-4-yl)-1-(tetrahydrofuran-3-yl)-1H-indazol-5-amine (2.73 g, 9.27 mmol, 100% yield). 1 H NMR (400 MHz, CDCl3) δ 8.61 (d, J = 5.2 Hz, 1H), 7.85 (s, 1H), 7.34 (s, 1H), 7.29 (d, J = 5.2 Hz, 1H), 7.25 (s, 1H), 7.05 (s, 1H), 5.25 - 5.19 (m, 1H), 4.26 - 4.20 (m, 1H), 4.19 - 4.16 (m, 2H), 4.01 - 3.96 (m, 1H), 2.65 (s, 3H), 2.52 - 2.45 (m, 2H); MS (ESI) m / z: 295.1 [M+1] + 。 2-(2,6- bis(oxo)piperidine -3- yl )-4-((6-(2- methylpyridine -4- yl )-1-((R)- tetrahydrofuran -3- yl )-1H- indazole -5- yl ) amino ) isoindoline -1,3- dione. To a solution of (R)-6-(2-methylpyridin-4-yl)-1-(tetrahydrofuran-3-yl)-1H-indazol-5-amine (2.730 g, 9.27 mmol) and 4-bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (3.130 g, 9.27 mmol) in dioxane (40 mL) was added potassium carbonate (3.840 g, 27.81 mmol) and chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) (0.365 g, 0.46 mmol). The mixture was degassed and purged with nitrogen. The resulting mixture was stirred at 110 °C for 12 h. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by reverse-phase preparative HPLC. The isolated material was lyophilized to give 2-(2,6-dioxopiperidin-3-yl)-4-((6-(2-methylpyridin-4-yl)-1-((R)-tetrahydrofuran-3-yl)-1H-indazol-5-yl)amino)isoindoline-1,3-dione trifluoroacetate (1026 mg, 1.86 mmol). 1 H NMR (400 MHz, DMSO-d 6 ) δ 11.13 (s, 1H), 8.65 (d, J= 6.0 Hz, 1H), 8.46 (s, 1H), 8.23 (s, 1H), 8.07 (s, 1H), 7.94 (s, 2H), 7.81 (d, J= 3.2 Hz, 1H), 7.42 - 7.38 (m, 1H), 7.08 (d, J= 7.2 Hz, 1H), 6.73 - 6.69 (m, 1H), 5.65 - 5.59 (m, 1H), 5.09 (dd, J= 5.2, 12.8 Hz, 1H), 4.17 - 4.10 (m, 2H), 3.98 - 3.92 (m, 2H), 2.95 - 2.86 (m, 1H), 2.64 - 2.63 (m, 1H), 2.60 (s, 3H), 2.48 - 2.46 (m, 1H), 2.44 - 2.37 (m, 2H), 2.08 - 2.03 (m, 1H); MS (ESI) m / z: 551.2 [M+1] + 2-((R)-2,6- bis(oxo)piperidine -3- yl )-4-((6-(2- methylpyridine -4- yl )-1-((R)- tetrahydrofuran -3- yl )-1H- indazole -5- yl ) amino ) isoindoline -1,3- dione. 2-(2,6-Bis(oxo)piperidin-3-yl)-4-((6-(2-methylpyridin-4-yl)-1-((R)-tetrahydrofuran-3-yl)-1H-indazol-5-yl)amino)isoindoline-1,3-dione (0.75 g, 1.36 mmol) was separated by chiral preparative SFC (70 - 70% isopropanol / acetonitrile). One of the two separated peaks was concentrated under reduced pressure to give 2-((R)-2,6-bis(oxo)piperidin-3-yl)-4-((6-(2-methylpyridin-4-yl)-1-((R)-tetrahydrofuran-3-yl)-1H-indazol-5-yl)amino)isoindoline-1,3-dione (0.33 g, 0.60 mmol, 44% yield). 1 H NMR (400 MHz, DMSO-d 6 ) δ 11.12 (s, 1H), 8.39 (d, J = 5.2 Hz, 1H), 8.32 (s, 1H), 8.18 (s, 1H), 7.93 (s, 1H), 7.89 (s, 1H), 7.43 - 7.42 (m, 1H), 7.42 - 7.39 (m, 1H), 7.33 (d, J = 4.8 Hz, 1H), 7.06 (d, J = 7.2 Hz, 1H), 6.78 (d, J = 8.8 Hz, 1H), 5.64 - 5.58 (m, 1H), 5.08 (dd, J = 12.8, 5.2 Hz, 1H), 4.14 - 4.09 (m, 2H), 3.95 - 3.90 (m, 2H), 2.94 - 2.85 (m, 1H), 2.63 - 2.58 (m, 2H), 2.47 - 2.46 (m, 1H), 2.43 (s, 3H), 2.40 - 2.36 (m, 1H), 2.07 - 2.02 (m, 1H); MS (ESI) m / z: 551.3 [M+1] + 。 2-((S)-2,6- bis(oxo)piperidine -3- yl )-4-((6-(2- methylpyridine -4- yl )-1-((R)- tetrahydrofuran -3- yl )-1H- indazole -5- yl ) amino ) isoindoline -1,3- dione. 2-(2,6-Dioxopiperidin-3-yl)-4-((6-(2-methylpyridin-4-yl)-1-((R)-tetrahydrofuran-3-yl)-1H-indazol-5-yl)amino)isoindoline-1,3-dione (0.75 g, 1.36 mmol) was separated by chiral preparative SFC (70 - 70% isopropanol / acetonitrile). One of the two separated peaks was concentrated under reduced pressure to give 2-((S)-2,6-dioxopiperidin-3-yl)-4-((6-(2-methylpyridin-4-yl)-1-((R)-tetrahydrofuran-3-yl)-1H-indazol-5-yl)amino)isoindoline-1,3-dione (0.40 g, 0.73 mmol, 53% yield). 1 H NMR (400 MHz, DMSO-d 6 ) δ 11.12 (s, 1H), 8.38 (d, J = 5.2 Hz, 1H), 8.32 (s, 1H), 8.18 (s, 1H), 7.92 (s, 1H), 7.89 (s, 1H), 7.42 (s, 1H), 7.41 - 7.39 (m, 1H), 7.32 - 7.31 (m, 1H), 7.07 (d, J = 6.8 Hz, 1H), 6.82 - 6.78 (m, 1H), 5.64 - 5.58 (m, 1H), 5.08 (dd, J = 12.8, 5.6 Hz, 1H), 4.16 - 4.07 (m, 2H), 3.96 - 3.88 (m, 2H), 2.94 - 2.85 (m, 1H), 2.63 - 2.58 (m, 2H), 2.43 (s, 3H), 2.40 - 2.36 (m, 2H), 2.07 - 2.02 (m, 1H); MS (ESI) m / z: 551.3 [M+1] + 。 Example 27 : (S)-2-(2,6- Dioxopiperidine -3- yl )-4-((1- Methyl -6-(2- methylpyridine -4- yl )-2- side oxy group -1,2,3,4- tetrahydroquinoline -7- yl ) amino ) isoindoline -1,3- dione 7- amino -6- bromo -3,4- dihydroquinoline -2(1H)- one. To a suspension of 7-amino-3,4-dihydroquinolin-2(1H)-one (5.00 g, 30.83 mmol) in a mixture of dichloromethane (100 mL) and methanol (25 mL) was added tetra-n-butylammonium tribromide (6.00 g, 13.87 mmol). The reaction mixture was stirred at 0 °C for two hours. The reaction mixture was partitioned between dichloromethane and a 10% aqueous solution of sodium thiosulfate. The organic layer was dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting crude residue was purified by column chromatography to give 7-amino-6-bromo-3,4-dihydroquinolin-2(1H)-one (1.00 g, 4.15 mmol, 13% yield). MS (ESI) m / z: 242.4[M+1] + 7- amino -6- bromo -1- methyl -3,4- dihydroquinoline -2(1H)- one. 7-Amino-6-bromo-3,4-dihydroquinolin-2(1H)-one (1.00 g, 4.15 mmol) was dissolved in tetrahydrofuran (15 mL) and cooled to 0 °C. Subsequently, potassium bis(trimethylsilyl)amide (1 M) (4.6 mL, 4.56 mmol) was added dropwise, followed by the dropwise addition of methyl iodide (0.65 g, 4.56 mmol). The mixture was stirred at 25 °C for 12 h. The reaction was quenched with saturated ammonium chloride solution (10 mL) and then partitioned between ethyl acetate and brine. The organic layer was dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting crude residue was purified by column chromatography to give 7-amino-6-bromo-1-methyl-3,4-dihydroquinolin-2(1H)-one as a yellow solid (0.80 g, 3.14 mmol, 75% yield). 1 H NMR (400 MHz, DMSO- d 6 ) δ 7.17 (s, 1H), 6.56 (s, 1H), 5.26 - 5.19 (m, 2H), 3.17 (s, 3H), 2.72 - 2.68 (m, 2H), 2.49 - 2.45 (m, 2H); MS (ESI) m / z: 255.1[M]. 7- amino -1- methyl -6-(2- methylpyridine -4- yl )-3,4- dihydroquinoline -2(1H)- one. To a mixture solution of 7-amino-6-bromo-1-methyl-3,4-dihydroquinolin-2(1H)-one (0.80 g, 3.14 mmol) in 1,4-dioxane (10 mL) and water (1 mL) was added 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.81 g, 3.70 mmol), dichloro(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) (0.25 g, 0.31 mmol), and potassium carbonate (1.29 g, 9.41 mmol). The suspension was degassed and purged with nitrogen. The mixture was stirred at 110 °C for 12 h. The reaction mixture was concentrated in vacuo and purified by silica gel column chromatography to give 7-amino-1-methyl-6-(2-methylpyridin-4-yl)-3,4-dihydroquinolin-2(1H)-one (0.60 g, 2.24 mmol, 71% yield). MS (ESI) m / z: 268.0[M+1] + 2-(2,6- bis(oxypiperidine) -3- yl )-4-((1- methyl -6-(2- methylpyridine -4- yl )-2- oxo -1,2,3,4- tetrahydroquinoline -7- yl ) amino ) isoindoline -1,3- dione. To a solution of 7-amino-1-methyl-6-(2-methylpyridin-4-yl)-3,4-dihydroquinolin-2(1H)-one (0.60 g, 2.24 mmol) in 1,4-dioxane (10 mL) was added 4-bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (0.83 g, 2.47 mmol), potassium carbonate (0.92 g, 6.73 mmol), and chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) (0.17 g, 0.22 mmol). The suspension was degassed and purged with nitrogen. The mixture was stirred at 115 °C for 12 h. The reaction mixture was filtered and the filtrate was concentrated, and purified by semi-preparative reverse phase HPLC. The collected eluent fractions were lyophilized to give 2-(2,6-dioxopiperidin-3-yl)-4-((1-methyl-6-(2-methylpyridin-4-yl)-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)isoindoline-1,3-dione (0.60 g, 1.15 mmol, 51% yield). MS (ESI) m / z: 524.2 [M+1] + (S)-2-(2,6- dioxopiperidin -3- yl )-4-((1- methyl -6-(2- methylpyridin -4- yl )-2- oxo -1,2,3,4- tetrahydroquinolin -7- yl ) amino ) isoindolin -1,3- dione. 2-(2,6-Dioxopiperidin-3-yl)-4-((1-methyl-6-(2-methylpyridin-4-yl)-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)isoindoline-1,3-dione (0.60 g, 1.15 mmol) was separated by chiral preparative SFC (40 - 40% isopropanol / acetonitrile). After separation, the peak (S)-2-(2,6-dioxopiperidin-3-yl)-4-((1-methyl-6-(2-methylpyridin-4-yl)-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)isoindoline-1,3-dione (261 mg, 0.49 mmol, 43% yield) was obtained. 1 H NMR (400 MHz, DMSO- d 6 ) δ 11.11 (s, 1H), 8.35 (d, J= 5.2 Hz, 1H), 8.33 (s, 1H), 7.49 - 7.43 (m, 1H), 7.38 (s, 1H), 7.32 (s, 1H), 7.23 (d, J= 5.2 Hz, 1H), 7.20 (s, 1H), 7.15 - 7.11 (m, 1H), 6.99 (d, J= 8.4 Hz, 1H), 5.08 (dd, J= 5.2, 12.8 Hz, 1H), 3.27 (s, 3H), 2.99 - 2.93 (m, 2H), 2.92 - 2.83 (m, 1H), 2.64(t, J= 7.2Hz, 2H), 2.60 - 2.55 (m, 1H), 2.54 (s, 1H), 2.41 (s, 3H), 2.07 - 1.99 (m, 1H); MS (ESI) m / z: 524.3[M+1] + Example 28 : 2-(2,6- Dioxopiperidine -3- yl )-4-((1- Methyl -6-(4- Methylthiazole -2- yl )-2- Side oxy group -1,2,3,4- Tetrahydroquinoline -7- yl ) Amino ) Isoindoline -1,3- Dione 7- Amino -1- Methyl -6-(4,4,5,5- Tetramethyl -1,3,2- Dioxaborolane -2- yl )-3,4- Dihydroquinoline -2(1H)- one. To a solution of 7-amino-6-bromo-1-methyl-3,4-dihydroquinolin-2(1H)-one (0.50 g, 1.96 mmol) and 4,4,4',4',5,5,5',5'-octamethyl-2,2'-di(1,3,2-dioxaborolane) (0.59 g, 2.35 mmol) in 1,4-dioxane (8 mL) was added potassium acetate (0.57 g, 5.88 mmol). The mixture was degassed and purged with nitrogen. To the mixture was added dichloro(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) (0.16 g, 0.20 mmol), and the mixture was stirred at 110 °C for 12 hours. The reaction mixture was filtered and the filtrate was concentrated. The resulting residue was purified by silica gel column chromatography to give 7-amino-1-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroquinolin-2(1H)-one (0.28 g, 0.93 mmol, 47% yield). MS (ESI) m / z: 303.4[M+1] + 7- Amino -1- Methyl -6-(4- Methylthiazole -2- yl )-3,4- Dihydroquinoline -2(1H)- one. To a solution of 7-amino-1-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroquinolin-2(1H)-one (0.20 g, 0.66 mmol) and 2-bromo-4-methylthiazole (0.14 g, 0.79 mmol) in 1,4-dioxane (1 mL) and water (0.2 mL) was added sodium carbonate (0.21 mg, 1.99 mmol). The mixture was degassed and purged with nitrogen. To the mixture was added dichloro(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) (0.06 mg, 0.07 mmol), and the reaction was stirred at 110 °C for 12 hours. The reaction mixture was filtered and the filtrate was concentrated. The resulting crude residue was purified by preparative TLC to give 7-amino-1-methyl-6-(4-methylthiazol-2-yl)-3,4-dihydroquinolin-2(1H)-one (0.06 g, 0.22 mmol, 33% yield). 1 H NMR (400 MHz, CDCl 3 ) δ 7.37 (s, 1H), 6.73 (s, 1H), 6.35 (s, 1H), 3.34 (s, 3H), 2.88 - 2.82 (m, 2H), 2.69 - 2.63 (m, 2H), 2.47 (s, 3H). 2-(2,6- Dioxopiperidinyl -3- yl )-4-((1- Methyl -6-(4- Methylthiazole -2- yl )-2- Dioxo -1,2,3,4- Tetrahydroquinoline -7- yl ) amino ) Isoindoline -1,3- dione. To a solution of 7-amino-1-methyl-6-(4-methylthiazol-2-yl)-3,4-dihydroquinolin-2(1H)-one (0.05 g, 0.18 mmol) in 1,4-dioxane (2 mL) was added 4-bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (0.068 g, 0.20 mmol), potassium carbonate (0.076 g, 0.55 mmol), and chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) (0.014 g, 0.02 mmol). The suspension was degassed and purged with nitrogen. The mixture was stirred at 115 °C for 12 h. The reaction mixture was filtered and the filtrate was concentrated. The resulting crude residue was purified by semi-preparative reverse-phase HPLC, and the collected eluate fractions were lyophilized to give 2-(2,6-dioxopiperidin-3-yl)-4-((1-methyl-6-(4-methylthiazol-2-yl)-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)isoindoline-1,3-dione (12 mg, 0.023 mmol, 12% yield). 1 H NMR (400 MHz, DMSO- d 6 ) δ 11.14 (s, 1H), 11.11 - 11.06 (m, 1H), 7.75 - 7.70 (m, 2H), 7.67 - 7.62 (m, 1H), 7.30 (d, J= 7.2 Hz, 1H), 7.28 (d, J= 0.8 Hz, 1H), 7.28 (s, 1H), 5.14 (dd, J= 5.4, 12.4 Hz, 1H), 3.27 (s, 3H), 2.96 (t, J = 7.2 Hz, 2H), 2.93 - 2.87 (m, 1H), 2.65 - 2.60 (m, 2H), 2.58 - 2.56 (m, 1H), 2.55 - 2.54 (m, 1H), 2.42 (s, 3H), 2.13 - 2.06 (m, 1H); MS (ESI) m / z: 530.0[M+1] + Example 29 : (S)-4-((6-(1- cyclopropyl -1H- pyrazol -4- yl )-1- methyl -2- side oxy -1,2,3,4- tetrahydroquinoline -7- yl ) amino )-2-(2,6- di side oxy piperidine -3- yl ) isoindoline -1,3- dione 7- amino -6-(1- cyclopropyl -1H- pyrazol -4- yl )-1- methyl -3,4- dihydroquinoline -2(1H)- one. To a mixture solution of 7-amino-6-bromo-1-methyl-3,4-dihydroquinolin-2(1H)-one (0.20 g, 0.78 mmol) in 1,4-dioxane (4 mL) and water (1 mL) was added 1-cyclopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole (0.20 g, 0.86 mmol), dichloro(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) (0.10 g, 0.12 mmol), and potassium carbonate (0.76 g, 2.35 mmol). The suspension was degassed and purged with nitrogen. The mixture was stirred at 110 °C for 12 h. The reaction mixture was dried over anhydrous sodium sulfate and then filtered. The filtrate was concentrated under reduced pressure and purified by silica gel column chromatography (5-15% methanol / dichloromethane) to give 7-amino-6-(1-cyclopropyl-1H-pyrazol-4-yl)-1-methyl-3,4-dihydroquinolin-2(1H)-one (0.25 g, 0.91 mmol, 100% yield). MS (ESI) m / z: 283.0 [M+1] + 。 3-((6-(1- cyclopropyl -1H- pyrazole -4- yl )-1- methyl -2- side oxy -1,2,3,4- tetrahydroquinoline -7- yl ) amino ) dimethyl phthalate. To a solution of 7-amino-6-(1-cyclopropylpyrazol-4-yl)-1-methyl-3,4-dihydroquinolin-2-one (0.197 g, 0.70 mmol) and dimethyl 3-bromophthalate (0.226 g, 0.83 mmol) in 1,4-dioxane (5 mL) was added cesium carbonate (0.680 g, 2.09 mmol) and (2-dicyclohexylphosphino-2',6'-diisopropoxybiphenyl)(2-amino-1,1'-biphenyl-2-yl)palladium(II) methanesulfonate (0.029 g, 0.04 mmol). The mixture was degassed and purged with nitrogen. The reaction mixture was stirred at 110 °C for 12 h. The reaction mixture was filtered and concentrated under reduced pressure. The resulting crude product was purified by preparative TLC to give dimethyl 3-((6-(1-cyclopropyl-1H-pyrazol-4-yl)-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)phthalate (0.127 g, 0.25 mmol, 38.4% yield). 1 H NMR (400 MHz, CDCl3) δ 7.26 (s, 2H), 7.24 (s, 1H), 7.07 (s, 1H), 7.05 (s, 1H), 7.03 (s, 1H), 7.01 (s, 1H), 6.93 (s, 1H), 3.90 (s, 3H); MS (ESI) m / z: 475.2 [M+1] + 3-((6-(1- cyclopropyl -1H- pyrazole -4- yl )-1- methyl -2- oxo -1,2,3,4- tetrahydroquinoline -7- yl ) amino ) phthalic acid. To a solution of dimethyl 3-((6-(1-cyclopropyl-1H-pyrazol-4-yl)-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)phthalate (0.170 g, 0.36 mmol) in water (1 mL) and methanol (3 mL) was added sodium hydroxide (0.043 g, 1.07 mmol). The mixture was stirred at 80 °C for 12 h. The mixture was adjusted to pH 3 with dilute hydrochloric acid and filtered. The filtrate was concentrated under reduced pressure to give the crude 3-((6-(1-cyclopropyl-1H-pyrazol-4-yl)-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)phthalic acid (0.088 g, 0.20 mmol, 55.0% yield). MS (ESI) m / z: 447.2 [M+1] + racemic -(4S)-5- amino -4-[4-[[6-(1- cyclopropylpyrazole -4- yl )-1- methyl -2- oxo -3,4- dihydroquinoline -7- yl ] amino ]-1,3- dioxo - isoindoline -2- yl ]-5- oxo - tert-butyl pentanoate. To a solution of 3-((6-(1-cyclopropyl-1H-pyrazol-4-yl)-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)phthalic acid (0.088 g, 0.20 mmol) in toluene (1.5 mL) and triethylamine (0.34 mL, 1.97 mmol) was added racemic-(4S)-4,5-diamino-5-oxo-valeric acid tert-butyl ester (0.040 g, 0.20 mmol). The mixture was stirred at 130 °C for 12 hours. The reaction mixture was concentrated under reduced pressure. The resulting residue was purified by preparative TLC to give racemic-(4S)-5-amino-4-[4-[[6-(1-cyclopropylpyrazol-4-yl)-1-methyl-2-oxo-3,4-dihydroquinolin-7-yl]amino]-1,3-dioxoisoindolin-2-yl]-5-oxo-valeric acid tert-butyl ester (0.069 g, 0.11 mmol, 57.1% yield). (S)-4-((6-(1- cyclopropyl -1H- pyrazole -4- yl )-1- methyl -2- oxo -1,2,3,4- tetrahydroquinoline -7- yl ) amino )-2-(2,6- dioxopiperidine -3- yl ) isoindoline -1,3- dione. A solution of tert-butyl (4S)-5-amino-4-[4-[[6-(1-cyclopropylpyrazol-4-yl)-1-methyl-2-oxo-3,4-dihydroquinolin-7-yl]amino]-1,3-dioxoisoindolin-2-yl]-5-oxopentanoate (0.069 g, 0.11 mmol) in acetonitrile (1 mL) was added with benzenesulfonic acid (0.018 g, 0.11 mmol). The mixture was stirred at 60 °C for 12 hours. The reaction mixture was extracted with dichloromethane (30 mL × 3) and saturated sodium bicarbonate solution (30 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by reverse-phase preparative HPLC to give (S)-4-((6-(1-cyclopropyl-1H-pyrazol-4-yl)-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (12 mg, 0.023 mmol, 20% yield). 1 H NMR (400 MHz, DMSO-d 6 ) δ 11.14 (s, 1H), 8.29 (s, 1H), 7.65 (s, 1H), 7.53 - 7.49 (m, 1H), 7.18 (d, J = 8.0 Hz, 1H), 7.12(s, 1H ), 7.0 (m, J = 8.0 Hz, 1H), 5.16 (dd, J = 4.0,12.0 Hz 12, 1H), 3.71 - 3.62 (m, 2H), 3.24 (s, 1H), 2.95 - 2.88 (m, 3H), 2.65 (s, 1H), 2.62 - 2.60 (m, 2H), 2.10 - 2.08 (m, 1H), 1.24 (s, 3H); MS (ESI) m / z: 539.2 [M+1] + Example 30 : (S)-4-((6-(1,3- dimethyl -1H- pyrazole -4- yl )-1- methyl -2- side oxy group -1,2,3,4- tetrahydroquinoline -7- group ) amino group )-2-(2,6- bis(side oxy)piperidine -3- group ) isoindoline -1,3- dione 7- amino group -6-(1,3- dimethylpyrazole -4- group )-1- methyl -3,4- dihydroquinoline -2- ketone. To a solution of 7-amino-6-bromo-1-methyl-3,4-dihydroquinolin-2-one (0.17 g, 0.67 mmol) and 1,3-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole (0.16 g, 0.73 mmol) in 1,4-dioxane (3 mL) and water (0.5 mL) was added potassium carbonate (0.27 g, 2.00 mmol). The mixture was degassed and purged with nitrogen. Dichloro(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) (0.05 g, 0.07 mmol) was added, and the mixture was stirred at 110 °C for 12 hours. The reaction mixture was filtered and the filtrate was concentrated. The resulting residue was purified by preparative TLC to give 7-amino-6-(1,3-dimethylpyrazol-4-yl)-1-methyl-3,4-dihydroquinolin-2-one (0.12 g, 0.44 mmol, 66% yield). MS (ESI) m / z: 271.2 [M+1] 3-((6-(1,3- dimethyl -1H- Pyrazole -4- -yl )-1- Methyl -2- Oxo -1,2,3,4- Tetrahydroquinoline -7- -yl ) Amino ) Dimethyl phthalate To a solution of 7-amino-6-(1,3-dimethyl-1H-pyrazol-4-yl)-1-methyl-3,4-dihydroquinolin-2-one (0.12 g, 0.44 mmol) and dimethyl 3-bromobenzene-1,2-dicarboxylate (0.13 g, 0.49 mmol) in 1,4-dioxane (3 mL) was added potassium carbonate (0.18 g, 1.33 mmol) and chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) (0.03 g, 0.04 mmol). The mixture was stirred at 110 °C for 12 h. The suspension was filtered and the filtrate was concentrated. The residue was purified by preparative TLC to give dimethyl 3-((6-(1,3-dimethyl-1H-pyrazol-4-yl)-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)phthalate (0.15 g, 0.32 mmol, 73% yield). MS (ESI) m / z: 463.1 [M+1] 3-((6-(1,3- Dimethyl -1H- Pyrazole -4- -yl )-1- Methyl -2- Oxo -1,2,3,4- Tetrahydroquinoline -7- -yl ) Amino ) Phthalic acid To a solution of dimethyl 3-((6-(1,3-dimethyl-1H-pyrazol-4-yl)-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)phthalate (0.15 g, 0.32 mmol) in methanol (3 mL) was added water (1.5 mL) containing sodium hydroxide (0.06 g, 1.63 mmol). The mixture was stirred at 80 °C for 12 h. The pH of the mixture was adjusted to 6 by addition of 1 M HCl. The resulting precipitated solid was collected by filtration, washed with water (20 ml) and dried in vacuo to give 3-((6-(1,3-dimethyl-1H-pyrazol-4-yl)-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)phthalic acid (0.11 g, 0.25 mmol, 78% yield). 1 H NMR (400 MHz, DMSO-d 6 ) δ 13.60 - 12.78 (m, 2H), 7.93 - 7.83 (m, 1H), 7.60 (s, 1H), 7.36 - 7.31 (m, 2H), 7.10 - 7.07 (m, 1H), 7.05 - 6.99 (m, 2H), 3.78 - 3.74 (m, 3H), 3.22 - 3.20 (m, 3H), 2.87 - 2.82 (m, 2H), 2.59 - 2.55 (m, 2H), 2.04 - 2.00 (m, 3H) (S)-5- amino -4-(4-((6-(1,3- dimethyl -1H- pyrazol -4- yl )-1- methyl -2- oxo -1,2,3,4- tetrahydroquinolin -7- yl ) amino )-1,3- bisoxoisoindoline -2- group )-5- tert-butyl 5-oxopentanoate To a solution of racemic-(4S)-4,5-diamino-5-oxopentanoic acid tert-butyl ester (0.052 g, 0.26 mmol) and 3-((6-(1,3-dimethyl-1H-pyrazol-4-yl)-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)phthalic acid (0.110 g, 0.25 mmol) in toluene (2.5 mL) was added triethylamine (0.44 mL, 2.53 mmol). The resulting mixture was stirred at 130 °C for 12 hours. The reaction mixture was concentrated under reduced pressure. The resulting residue was purified by preparative TLC to give tert-butyl (S)-5-amino-4-(4-((6-(1,3-dimethyl-1H-pyrazol-4-yl)-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)-1,3-dioxoisoindolin-2-yl)-5-oxopentanoate (0.090 g, 0.15 mmol, 59.2% yield). MS (ESI) m / z: 601.3 [M+1] (S)-4-((6-(1,3- dimethyl -1H- pyrazole -4- group )-1- methyl -2- oxo -1,2,3,4- tetrahydroquinoline -7- group ) amino )-2-(2,6- dioxopiperidine -3- group ) isoindoline -1,3- dione. To a solution of tert-butyl (S)-5-amino-4-(4-((6-(1,3-dimethyl-1H-pyrazol-4-yl)-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)-1,3-dioxoisoindolin-2-yl)-5-oxopentanoate (0.09 g, 0.15 mmol) in acetonitrile (1.5 mL) was added benzenesulfonic acid (0.047 g, 0.30 mmol). The mixture was stirred at 60 °C for 12 hours. The reaction mixture was quenched with dichloromethane (20 ml) and sodium bicarbonate (saturated aqueous solution, 10 mL), and then extracted with dichloromethane (50 mL × 3). The combined organic layers were dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure. The separated product was lyophilized to give (S)-4-((6-(1,3-dimethyl-1H-pyrazol-4-yl)-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (0.07 g, 0.13 mmol, 88% yield). 1 H NMR (400 MHz, DMSO-d 6 ) δ 11.13 - 11.10 (m, 1H), 8.06 - 8.00 (m, 1H), 7.65 - 7.61 (m, 1H), 7.58 - 7.52 (m, 1H), 7.30 - 7.27 (m, 1H), 7.20 - 7.16 (m, 3H), 5.12 - 5.06 (m, 1H), 3.74 - 3.70 (m, 3H), 3.27 (s, 3H), 2.93 - 2.86 (m, 3H), 2.60 (br s, 4H), 2.09 - 2.05 (m, 1H), 2.04 (s, 3H). MS (ESI) m / z: 527.2[M+1]. Example 31 : (S)-4-((6-(1,5- dimethyl -6- oxo -1,6- dihydropyridine -3- yl )-1- methyl -2- Side oxy group -1,2,3,4- Tetrahydroquinoline -7- Group ) Amino group )-2-(2,6- Dioxide piperidine -3- Group ) Isoindoline -1,3- Dione 7- Amino group -6-(1,5- Dimethyl -6- Side oxy group -1,6- Dihydropyridine -3- Group )-1- Methyl -3,4- Dihydroquinoline -2(1H)- Ketone. To a solution of potassium carbonate (0.48 g, 3.5 mmol) in 1,4-dioxane (3 mL) and water (0.3 mL) was added dichloro(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) (0.048 g, 0.06 mmol), 7-amino-6-bromo-1-methyl-3,4-dihydroquinolin-2(1H)-one (0.300 g, 1.18 mmol), and 1,3-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one (0.293 g, 1.18 mmol). The suspension was degassed and purged with nitrogen. The mixture was stirred at 110 °C for 12 hours. The reaction mixture was concentrated in vacuo and purified by silica gel column chromatography (5-15% methanol / dichloromethane) to give 7-amino-6-(1,5-dimethyl-6-side oxy-1,6-dihydropyridin-3-yl)-1-methyl-3,4-dihydroquinolin-2(1H)-one (0.15 g, 0.50 mmol, 42% yield). MS (ESI) m / z: 298.1[M+1] + 3-((6-(1,5- dimethyl -6- side oxy group -1,6- dihydropyridine -3- group )-1- methyl -2- side oxy group -1,2,3,4- tetrahydroquinoline -7- group ) amino group ) Dimethyl phthalate. To a solution of 7-amino-6-(1,5-dimethyl-6-side oxy group-1,6-dihydropyridine-3-yl)-1-methyl-3,4-dihydroquinolin-2(1H)-one (0.150 g, 0.50 mmol) and dimethyl 3-bromophthalate (0.165 g, 0.61 mmol) in 1,4-dioxane (1 mL) was added cesium carbonate (0.492 g, 1.51 mmol) and (2-dicyclohexylphosphino-2,6-diisopropoxy-1,1-biphenyl)(2-amino-1,1-biphenyl-2-yl)palladium(II) (0.042 g, 0.05 mmol). The mixture was degassed and purged with nitrogen. The resulting mixture was stirred under nitrogen at 110 °C for 12 hours. The reaction mixture was filtered and the filtrate was concentrated, and purified by semi-preparative reverse-phase HPLC (45 - 65% acetonitrile / water, 0.1% trifluoroacetic acid modifier). The isolated eluate was lyophilized to give dimethyl 3-((6-(1,5-dimethyl-6-side oxy group-1,6-dihydropyridine-3-yl)-1-methyl-2-side oxy group-1,2,3,4-tetrahydroquinolin-7-yl)amino)phthalate (0.05 g, 0.10 mmol, 20% yield). MS (ESI) m / z: 490.2[M+1] + 3-((6-(1,5- dimethyl -6- side oxy group -1,6- Dihydropyridine -3- yl )-1- methyl -2- side oxy -1,2,3,4- tetrahydroquinoline -7- yl ) amino ) phthalic acid. To a solution of dimethyl 3-((6-(1,5-dimethyl-6-side oxy-1,6-dihydropyridin-3-yl)-1-methyl-2-side oxy-1,2,3,4-tetrahydroquinolin-7-yl)amino)phthalate (0.050 g, 0.10 mmol) in methanol (1 mL) was added a solution of sodium hydroxide (0.041 g, 1.02 mmol) in water (1 mL). The mixture was stirred at 80 °C for 12 hours. The reaction mixture was added to water (10 mL) and the pH was adjusted to 6. The resulting suspension was filtered and the solid obtained was dried under reduced pressure. The filtrate was extracted with dichloromethane (20 mL × 3) and water (20 mL), and the combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure to give 3-((6-(1,5-dimethyl-6-side oxy-1,6-dihydropyridin-3-yl)-1-methyl-2-side oxy-1,2,3,4-tetrahydroquinolin-7-yl)amino)phthalic acid (0.04 g, 0.087 mmol, 85% yield). MS (ESI) m / z: 462.1[M+1] + . (S)-5- amino -4-(4-((6-(1,5- dimethyl -6- side oxy -1,6- dihydropyridine -3- yl )-1- methyl -2- side oxy -1,2,3,4- tetrahydroquinoline -7- radical ) amino )-1,3- bis(oxo)isoindoline -2- radical )-5- tert-butyl 5-(oxo)valerate. To a solution of 3-((6-(1,5-dimethyl-6-(oxo)-1,6-dihydropyridin-3-yl)-1-methyl-2-(oxo)-1,2,3,4-tetrahydroquinolin-7-yl)amino)phthalic acid (0.040 g, 0.09 mmol) and (S)-tert-butyl 4,5-diamino-5-(oxo)valerate (0.018 g, 0.09 mmol) in toluene (0.5 mL) was added triethylamine (0.15 mL, 0.87 mmol). The resulting mixture was stirred at 130 °C for 12 h. The reaction mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give (S)-tert-butyl 5-amino-4-(4-((6-(1,5-dimethyl-6-(oxo)-1,6-dihydropyridin-3-yl)-1-methyl-2-(oxo)-1,2,3,4-tetrahydroquinolin-7-yl)amino)-1,3-bis(oxo)isoindolin-2-yl)-5-(oxo)valerate (0.040 g, 0.06 mmol, 73.5% yield). MS (ESI) m / z: 628.3[M+1] + (S)-4-((6-(1,5- dimethyl -6- (oxo) -1,6- dihydropyridine -3- radical )-1- methyl -2- (oxo) -1,2,3,4- tetrahydroquinoline -7- radical ) amino )-2-(2,6- bis(oxo)piperidine -3- base ) isoindoline -1,3- dione. To a solution of (S)-5-amino-4-(4-((6-(1,5-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)-1,3-dioxoisoindolin-2-yl)-5-oxopentanoic acid tert-butyl ester (0.040 g, 0.06 mmol) in acetonitrile (2 mL) was added benzenesulfonic acid (0.023 g, 0.14 mmol). The resulting mixture was stirred at 60 °C under nitrogen for 12 hours. The reaction mixture was quenched with dichloromethane (20 ml) and sodium bicarbonate (saturated aqueous solution, 10 mL), and then extracted with dichloromethane (30 mL × 3). The combined organic layers were dried over anhydrous sodium sulfate, then filtered, and the filtrate was concentrated under reduced pressure. The crude product was further purified by chiral preparative SFC (40 - 40% isopropanol / acetonitrile). After separation, the main peak was lyophilized to give (S)-4-((6-(1,5-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (28.59 mg, 0.0516 mmol, 72.0% yield). 1 H NMR (400 MHz, DMSO-d 6 ) δ 11.11 (s, 1H), 8.30 (s, 1H), 7.69 (d, J = 2.4 Hz, 1H), 7.53 - 7.47 (m, 1H), 7.37 (d, J = 1.2 Hz, 1H), 7.29 (s, 1H), 7.18 - 7.13 (m, 2H), 7.02 (t, J = 8.4 Hz, 1H), 5.10 (dd, J = 5.6, 12.8 Hz, 1H), 3.39 (s, 3H), 3.26 (s, 3H), 2.95 - 2.90 (m, 2H), 2.90 - 2.83 (m, 1H), 2.64 - 2.56 (m, 4H), 2.07 - 2.00 (m, 1H), 1.90 (s, 3H); MS (ESI) m / z: 554.2[M+1] + 。 Example 32 : (S)-2-(2,6- bis(oxo)piperidine -3- yl )-4-((1- methyl -6-(2- methylpyridine -4- yl )-1H- indazole -5- yl ) amino ) isoindoline -1,3- dione 6- bromo -1- methyl -5- nitro -1H- indazole. To a 500 mL three-necked flask, 4-bromo-2-fluoro-5-nitrobenzaldehyde (10.0 g, 40.3 mmol), potassium carbonate (8.4 g, 60.8 mmol), isopropanol (80 mL), and water (40 mL) were added. The mixture was stirred at 41 °C for 1 hour, and methylhydrazine (11.7 g, 101.8 mmol) was added dropwise. The resulting mixture was heated to 77 °C and stirred for 6 hours. The mixture was cooled to 20 °C and water (150 mL) was added. The mixture was stirred for 1 hour and filtered. The separated solid was washed with water (20 mL × 3) and dried under reduced pressure to give 6-bromo-1-methyl-5-nitro-1H-indazole (6.7 g, 26.2 mmol, 64% yield). 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.61 (s, 1H), 8.33 (d, J= 2.4 Hz, 2H), 4.11 (s, 3H). 1- methyl -6-(2- methylpyridine -4- yl )-5- nitro -1H- indazole. To a solution of 6-bromo-1-methyl-5-nitro-1H-indazole (10.0 g, 39.0 mmol) and 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (8.7 g, 39.8 mmol) in dioxane (100 mL) and water (10 mL), potassium carbonate (16.0 g, 115.9 mmol) and dichloro(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloromethane adduct (0.16 g, 0.20 mmol) were added. The resulting mixture was stirred under nitrogen at 110 °C for 12 hours. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give 1-methyl-6-(2-methylpyridin-4-yl)-5-nitro-1H-indazole (9 g, 33.5 mmol, 85% yield). 11H NMR (400 MHz, CDCl3) δ 8.57 (d, J = 5.2 Hz, 1H), 8.53 (s, 1H), 8.22 (s, 1H), 7.33 (s, 1H), 7.18 (s, 1H), 7.12 (d, J = 4.8 Hz, 1H), 4.15 (s, 3H), 2.64 (s, 3H); MS (ESI) m / z: 269.3[M+1] + 。 1- methyl -6-(2- methylpyridine -4- yl )-1H- indazole -5- amine. To a solution of 1-methyl-6-(2-methylpyridin-4-yl)-5-nitro-1H-indazole (9.0 g, 33.5 mmol) in ethanol (90 mL) and water (30 mL) were added ammonium chloride (9.0 g, 168.2 mmol) and iron powder (6.0 g, 107.1 mmol). The resulting mixture was stirred at 70 °C for 12 h. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The resulting residue was extracted with water (200 mL) and ethyl acetate (3 × 200 mL). The combined organic phases were dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to give 1-methyl-6-(2-methylpyridin-4-yl)-1H-indazol-5-amine (6.3 g, 26.4 mmol, 78% yield). 1 1H NMR (400 MHz, CDCl3) δ 8.60 (d, J = 4.8 Hz, 1H), 7.81 (s, 1H), 7.35 (s, 1H), 7.30 (d, J = 5.2 Hz, 1H), 7.16 (s, 1H), 7.04 (s, 1H), 4.03 (s, 3H), 2.65 (s, 3H); MS (ESI) m / z: 239.1[M+1]+. 3-((1- methyl -6-(2- methylpyridine -4- yl )-1H- Indazole -5- yl ) Amino ) Dimethyl phthalate. To a solution of 1-methyl-6-(2-methylpyridin-4-yl)-1H-indazole-5-amine (5.3 g, 22.2 mmol) and dimethyl 3-bromophthalate (6.2 g, 22.7 mmol) in dioxane (60 mL) was added cesium carbonate (21.6 g, 66.7 mmol) and (2-dicyclohexylphosphino-2,6-diisopropoxybiphenyl)(2-amino-1,1'-biphenyl-2-yl)palladium(II) (0.93 g, 1.11 mmol). The resulting mixture was stirred under nitrogen at 110 °C for 12 hours. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give dimethyl 3-((1-methyl-6-(2-methylpyridin-4-yl)-1H-indazol-5-yl)amino)phthalate (8.0 g, 18.5 mmol, 83% yield). 1 H NMR (400 MHz, CDCl3) δ 8.49 (d, J= 5.2 Hz, 1H), 8.06 (s, 1H), 7.97 (s, 1H), 7.70 (s, 1H), 7.40 (s, 1H), 7.27 (s, 1H), 7.23 - 7.18 (m, 2H), 7.13 (d, J= 5.2 Hz, 1H), 7.00 (d, J= 8.4 Hz, 1H), 6.94 (d, J= 7.2 Hz, 1H), 4.12 (s, 3H), 3.86 (s, 3H), 3.78 (s, 3H), 2.56 (s, 3H); MS (ESI) m / z: 431.2 [M+1] + 。 3-((1- Methyl -6-(2- Methylpyridine -4- yl )-1H- Indazole -5- yl ) Amino ) Phthalic acid. To a solution of dimethyl 3-((1-methyl-6-(2-methylpyridin-4-yl)-1H-indazol-5-yl)amino)phthalate (8.0 g, 18.58 mmol) in methanol (90 mL) was added a solution of sodium hydroxide (7.43 g, 185.85 mmol) in water (30 mL). The resulting mixture was stirred at 80 °C for 12 h. The reaction mixture was added to water (300 mL) and the resulting suspension was filtered. The solid thus obtained was dissolved in methanol (800 mL), and then adjusted to pH = 4 with aqueous HCl solution (6 M). The solution was concentrated under reduced pressure. The filtrate was adjusted to pH = 4 with aqueous HCl solution (6 M). The resulting precipitate was separated by suction filtration and dried under reduced pressure. The separated substances were combined to give 3-((1-methyl-6-(2-methylpyridin-4-yl)-1H-indazol-5-yl)amino)phthalic acid (4.0 g, 9.94 mmol, 53% yield). 1 H NMR (400 MHz, DMSO-d 6 ) δ 13.51 - 12.72 (m, 2H), 8.41 (d, J= 5.2 Hz, 1H), 8.21 (s, 1H), 8.05 (s, 1H), 7.76 (s, 1H), 7.73 (s, 1H), 7.38 (s, 1H), 7.28 (d, J= 5.2 Hz, 1H), 7.18 (t, J= 8.0 Hz, 1H), 6.85 (d, J= 7.2 Hz, 1H), 6.79 (d, J= 8.4 Hz, 1H), 4.09 (s, 3H), 2.47 (s, 3H); MS (ESI) m / z: 403.2 [M+1] + (S)-5- Amino -4-(4-((1- Methyl -6-(2- Methylpyridine -4- yl )-1H- Indazole -5- yl ) Amino )-1,3- Dioxoisoindoline -2- yl )-5- Oxypentanoic acid tert-butyl ester. To a solution of 3-((1-methyl-6-(2-methylpyridin-4-yl)-1H-indazol-5-yl)amino)phthalic acid (4.0 g, 9.94 mmol) in toluene (60 mL) was added (S)-4,5-diamino-5-oxypentanoic acid tert-butyl ester (2.01 g, 9.94 mmol) and triethylamine (17 mL, 99.4 mmol). The resulting mixture was stirred at 130 °C for 12 hours. The reaction mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give (S)-5-amino-4-(4-((1-methyl-6-(2-methylpyridin-4-yl)-1H-indazol-5-yl)amino)-1,3-dioxoisoindolin-2-yl)-5-oxypentanoic acid tert-butyl ester (2.83 g, 4.97 mmol, 50% yield). 1 H NMR (400 MHz, CDCl3) δ 8.49 (d, J = 4.8 Hz, 1H), 8.03 (s, 1H), 7.86 (s, 1H), 7.81 (s, 1H), 7.44 (s, 1H), 7.39 (t, J = 7.6 Hz, 1H), 7.23 (s, 1H), 7.15 (d, J = 7.2 Hz, 2H), 7.01 (d, J = 8.8 Hz, 1H), 6.37 - 6.12 (m, 1H), 5.54 - 5.33 (m, 1H), 4.78 (t, J = 7.2 Hz, 1H), 4.14 (s, 3H), 2.57 (s, 3H), 2.52 - 2.44 (m, 2H), 2.36 - 2.26 (m, 2H), 1.43 (s, 9H); MS (ESI) m / z: 569.3 [M+1] + (S)-2-(2,6- bis(oxo)piperidin- 3- yl )-4-((1- methyl -6-(2- methylpyridin- 4- yl )-1H- indazole -5- yl ) amino ) isoindoline -1,3- dione. To a solution of tert-butyl (S)-5-amino-4-(4-((1-methyl-6-(2-methylpyridin-4-yl)-1H-indazol-5-yl)amino)-1,3-bis(oxo)isoindolin-2-yl)-5-oxopentanoate (2.83 g, 4.98 mmol) in acetonitrile (30 mL) was added benzenesulfonic acid (2.36 g, 14.93 mmol). The resulting mixture was stirred at 60 °C for 12 h. The reaction mixture was concentrated under reduced pressure. The residue was extracted with dichloromethane (200 mL × 3) and sodium bicarbonate (200 mL). The combined organic layers were dried over anhydrous sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The crude product was purified by preparative HPLC and lyophilized to give (S)-2-(2,6-bis(oxo)piperidin-3-yl)-4-((1-methyl-6-(2-methylpyridin-4-yl)-1H-indazol-5-yl)amino)isoindoline-1,3-dione (1.80 g, 3.64 mmol, 73% yield) as a yellow solid. 1 H NMR (400 MHz, DMSO-d 6) δ 11.13 (s, 1H), 8.68 - 8.64 (m, 1H), 8.46 (s, 1H), 8.17 (s, 1H), 8.00 - 7.94 (m, 2H), 7.93 (s, 1H), 7.84 (s, 1H), 7.42 - 7.38 (m, 1H), 7.08 (d, J= 7.2 Hz, 1H), 6.70 - 6.66 (m, 1H), 5.09 (dd, J= 5.2, 12.8 Hz, 1H), 4.15 (s, 3H), 2.94 - 2.87 (m, 1H), 2.64 (s, 1H), 2.60 (d, J= 2.0 Hz, 3H), 2.60 - 2.58 (m, 1H), 2.08 - 2.01 (m, 1H); MS (ESI) m / z: 495.2 [M+1] + 。 In vitro analysis HbF Induction analysis Expansion, differentiation, and maturation of GCSF-mobilized human CD34 + (STEMCELL Technologies Inc.) cells into erythroid lineage cells (Moutouh-de Parseval LA et al., Pomalidomide and lenalidomide regulate erythropoiesis and fetal hemoglobin production in human CD34+ cells. J Clin Invest. January 2008;118(1):248-58). In the first stage, GCSF-mobilized human CD34 + cells were cultured using StemSpan™-XF (STEMCELL Technologies Inc.) medium supplemented with 1X BIT 9500, penicillin-streptomycin (50 U / mL), 100 ng / mL recombinant human (rh) SCF, 100 ng / mL rh Flt3-L, 20 ng / mL rh IL-3, and 10 ng / mL rh EPO, and the cells were incubated at 37 °C, 5% CO 2 Maintain the exponential growth phase for 7 days to support amplification and progenitor cell differentiation prior to the second stage and compound treatment. In the second stage, change the culture medium to StemSpan™-XF medium supplemented with 1X BIT 9500, penicillin-streptomycin (50 U / mL), 50 ng / mL rh SCF, and 40 ng / mL rh EPO to promote further differentiation and maturation of erythrocytes and initiate compound treatment. The compounds are aliquoted at a final concentration of 1 µM and a final DMSO amount of 0.1%. Fresh compounds are re-applied and the cell density is kept constant every 2 days. After 7 days, flow cytometry is used to evaluate cell viability and fetal hemoglobin expression. For viability analysis, the eBioscience™ Fixable Viability Dye eFluor™ 780 (1:1000, eBioscience; catalog number 65-0865-14) is added to the cells and kept in the dark for 10 minutes. For fetal hemoglobin (HbF) analysis, following the manufacturer's instructions, the cells are fixed and permeabilized using the Fixation Buffer (BioLegend; catalog number 420801) and the Intracellular Staining Permeabilization Buffer (BioLegend, catalog number 420201). During the permeabilization step, the cells are stained with PE-labeled mouse anti-human fetal hemoglobin (1:10, clone 2D12; BD Biosciences, catalog number BDB560041) and incubated in the dark at room temperature for 20 minutes. PE-labeled mouse anti-IgG k (1:10 clone MOPC-21; BD Biosciences, catalog number BDB551436) is used as an isotype control. The Attune NXT flow cytometer (Thermofisher) was used to measure viability, cell count, and fetal hemoglobin (HbF) content, and the FCS express software (De Novo Software) was used to analyze the data. In Table 1 below, the effects of the compounds of formula (I), formula (I'), formula (II), formula (II'), and formula (III) on % live cells, live cell count, % HbF-positive cells, and median fluorescence intensity (MFI) of the HbF-positive cell population can be seen compared to the DMSO control. All gates were set using isotype negative controls. The baseline % HbF-positive cells of the DMSO-treated control cells was 15%. Compounds of formula (I), formula (I'), formula (II), formula (II'), and formula (III) with HbF induction between 66% and 100% were level A. Compounds of formula (I), formula (I'), formula (II), formula (II'), and formula (III) with HbF induction between 33% and 66% were level B. Compounds of formula (I), formula (I'), formula (II), formula (II'), and formula (III) with HbF induction % less than 33% were level C. Some compounds of formula (I), formula (I'), formula (II), formula (II'), and formula (III) with HbF induction % values of 0 - 33% (activity level C), between 33% and 66% (activity level B), and between 67% and 100% (activity level A) are shown in Table 2 below. WIZ analysis and ZBTB7A EC 50 analysis The HiBiT degradation assay of WIZ and ZBTB7A in HUDEP-2 cells was performed as described below. HUDEP-2 cells engineered to express the HiBiT tag in the WIZ (Widely interspaced zinc finger) or ZBTB7A (Zinc Finger And BTB Domain Containing 7A) protein were maintained in StemSpan SFEM II medium supplemented with penicillin-streptomycin (50 U / mL), rhSCF (50 ng / mL), rhEPO (3 IU / mL), dexamethasone (0.4 µg / mL), and doxycycline (1 µg / mL) in low-attachment flasks. Before starting the assay, cell count and viability were measured by trypan blue exclusion using a Vi-cell XR cell viability analyzer. For the HUDEP-2 WIZ HiBiT assay, the cells were transferred to a 50 mL conical flask and centrifuged at 500 g for five minutes. The cells were resuspended at a density of 1.0 × 10 6 cells / mL in fresh StemSpan SFEM II medium supplemented with penicillin-streptomycin (50 U / mL), rhSCF (50 ng / mL), rhEPO (3 IU / mL), dexamethasone (0.4 µg / mL), and doxycycline (1 µg / mL). Forty microliters of the cell suspension was dispensed into a 384-well low-profile white flat-bottom polystyrene TC-treated microplate containing pre-dispensed compounds using a VIAFLO 384 liquid handler and placed in a 37 °C incubator containing 5% CO 2 . Each compound was dispensed in duplicate and had a final DMSO concentration of 0.1%. After 24 hours of treatment, 40 µL of the Nano-Glo HiBiT Lysis Detection System reagent was dispensed into each well using a VIAFLO 384 liquid handler. The plate was incubated at room temperature for 25 minutes, and luminescence was read as relative light units using an EnVision plate reader. After normalizing against 10 different concentrations of DMSO controls at 10, 3.33, 1.11, 0.37, 0.12, 0.04, 0.0137, 0.0046, 0.0015, and 0.0005 µM respectively, curves calculated using dotmatics software were used to calculate the EC 50 and Y-min values. For HUDEP-2 ZBTB7A HiBiT analysis, cell count and viability were measured by trypan blue exclusion using a Vi-cell XR cell viability analyzer, and the cells were transferred to a 50 mL conical flask and centrifuged at 500 g for five minutes. The cells were resuspended in fresh IMDM medium supplemented with L-glutamine (1×), penicillin-streptomycin (50 U / mL), holo-transferrin (330 μg / mL), heparin (2 IU / mL), recombinant human insulin (10 μg / mL), rhEPO (3 IU / mL), rhSCF (100 ng / mL) + Dox (1 μg / mL), and 5% human plasma in a low-attachment flask, and the flasks were placed in a 37 °C incubator containing 5% CO 2 2. After 48 hours, cell count and viability were measured by trypan blue exclusion using a Vi-cell XR cell viability analyzer. The HUDEP-2 ZBTB7A cells were transferred to a 50 mL conical flask, centrifuged at 500 g for five minutes, and resuspended at a density of 1.0 × 10 6 cells / mL in IMDM medium supplemented with L-glutamine (1×), penicillin-streptomycin (50 U / mL), holo-transferrin (330 μg / mL), heparin (2 IU / mL), recombinant human insulin (10 μg / mL), rhEPO (3 IU / mL), rhSCF (100 ng / mL) + Dox (1 μg / mL), and 5% human plasma. Forty microliters of cell suspension was dispensed into a 384-well low-profile white flat-bottom polystyrene TC-treated microplate containing pre-dispensed compounds using a VIAFLO 384 liquid handler, and placed in a 37 °C incubator containing 5% CO 2 2. Each compound was dispensed in duplicate and had a final DMSO concentration of 0.1%. After 24 hours of treatment, 40 μL of Nano-Glo HiBiT lysis detection system reagent was dispensed into each well using a VIAFLO 384 liquid handler. The plate was incubated at room temperature for 25 minutes, and luminescence was read as relative light units using an EnVision plate reader. After normalizing against 10 different concentrations of DMSO controls at 10, 3.33, 1.11, 0.37, 0.12, 0.04, 0.0137, 0.0046, 0.0015, and 0.0005 μM respectively, curves calculated using dotmatics software were used to calculate EC 50 and Y-min values. WIZ EC 50 Compounds of formula (I), formula (I'), formula (II), formula (II') and formula (III) with < 0.01 μM are level D. WIZ EC 50 Compounds of formula (I), formula (I'), formula (II), formula (II') and formula (III) with > 0.01 μM to 0.1 μM are level E. WIZ EC 50 Compounds of formula (I), formula (I'), formula (II), formula (II') and formula (III) with > 0.1 μM are level F. WIZ EC 50 Values < 0.01 μM (activity level D), WIZ EC 50 Certain compounds of formula (I), formula (I'), formula (II), formula (II') and formula (III) with > 0.01 μM to 0.1 (activity level E) and < 0.01 μM (activity level F) are shown in Table 2 below. ZBTB7A EC 50 Compounds of formula (I), formula (I'), formula (II), formula (II') and formula (III) with < 0.03 μM are level G. ZBTB7A EC 50 Compounds of formula (I), formula (I'), formula (II), formula (II') and formula (III) with > 0.03 μM to 0.1 μM are level H. ZBTB7A EC 50 Compounds of formula (I), formula (I'), formula (II), formula (II') and formula (III) with > 0.1 μM are level I. ZBTB7A EC 50 Values < 0.01 μM (activity level G), ZBTB7A EC 50 Certain compounds of formula (I), formula (I'), formula (II), formula (II') and formula (III) with > 0.01 μM to 0.1 (activity level H) and < 0.01 μM (activity level I) are shown in Table 2 below. Table 2 Numerous references have been cited, the disclosures of which are incorporated herein by reference in their entirety.

Claims

1. A compound of formula (III) or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein: (III) Q'' is H or CH3; R12 is: , where Q3 is selected from H, Cl or F; Q4 is selected from H, CH3 or CH(F)2; Q5 is selected from H, CH3 or OCH3; and Q6 is selected from H or F.

2. The compound of claim 1 or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein Q'' is H.

3. The compound of claim 1 or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein Q3 is F.

4. The compound of claim 1 or its pharmaceutically acceptable salt, tautomer or stereoisomer, wherein Q5 is OCH3 or CH3.

5. A compound of claim 1 or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof, wherein Q3 is H, Q4 is H, Q5 is CH3, and Q6 is H; Q3 is H, Q4 is CH(F)2, Q5 is H, and Q6 is H; Q3 is F, Q4 is CH3, Q5 is H, and Q6 is H; Q3 is F, Q4 is H, Q5 is CH3, and Q6 is H; Q3 is Cl, Q4 is CH3, Q5 is H, and Q6 is H; Q3 is H, Q4 is CH3, Q5 is CH3, and Q6 is H; Q3 is H, Q4 is CH3, Q5 is CH3, and Q6 is H; Q3 is H, Q4 is CH3, Q5 is OCH3, and Q6 is H; Q3 is F, Q4 is H, Q5 is OCH3, and Q6 is H; or Q3 is H, Q4 is H, Q5 is OCH3, and Q6 is F.

6. A compound or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein the compound is selected from: , , , , , , , , and.

7. The compound of claim 6 or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein the compound is: .

8. The compound of claim 6 or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein the compound is: .

9. The compound of claim 6 or its pharmaceutically acceptable salt, tautomer or stereoisomer is: or its pharmaceutically acceptable salt.

10. The compound of claim 6 or its pharmaceutically acceptable salt, tautomer or stereoisomer is: or its pharmaceutically acceptable salt.

11. A compound having the following structure, .

12. A compound having the following structure, .

13. A pharmaceutically acceptable salt of a compound having the following structure, .

14. A pharmaceutically acceptable salt of a compound having the following structure.

15. A pharmaceutical composition comprising an effective amount of a compound of any one of claims 1 to 10 or a pharmaceutically acceptable salt thereof, a tautomer or stereoisomer thereof, a pharmaceutically acceptable salt thereof of a compound of claim 11 or 12 or a compound of claim 13 or 14, and a pharmaceutically acceptable carrier, excipient or mediator.

16. Use of a compound of any one of claims 1 to 10 or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, a compound of claim 11 or 12, a pharmaceutically acceptable salt of a compound of claim 13 or 14, or a pharmaceutical composition of claim 15 for the preparation of a pharmaceutical product, wherein the pharmaceutical product is used to induce HbF expression in cells and / or reduce ZBTB7A expression in cells and / or reduce WIZ expression in cells.

17. Use of a compound of any one of claims 1 to 10 or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, a compound of claim 11 or 12, a pharmaceutically acceptable salt of a compound of claim 13 or 14 or a pharmaceutical composition of claim 15 for the preparation of a pharmaceutical product, wherein the pharmaceutical product is for the treatment of heme disorders.

18. As claimed in claim 17, wherein the pharmaceutical product is used in combination with a second active agent and / or therapy.

19. As claimed in claim 18, wherein the second active agent and / or therapy is luspatercept, voxelotor, crizanlizumab-tmca, hydroxyurea, L-glutamic acid, etavipivat, mitapivat, osivelotor, inclacumab, blood transfusion, stem cell transplantation, bone marrow transplantation, or gene therapy.

20. As claimed in claim 19, wherein the second therapy is gene therapy, and the gene therapy is CRISPR therapy.

21. As requested in claim 17, wherein the heme disorder is anemia, sickle cell disease or thalassemia.

22. As requested in claim 21, wherein the heme disorder is α-thalassemia or β-thalassemia.

23. As requested in claim 21, wherein the heme lesion is sickle cell disease.