COMPOUNDS FOR MODULATING SYK ACTIVITY AND E3 UBIQUITIN LIGASE ACTIVITY CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims priority to U.S. Prov. Patent App. No.63/383,454, titled “COMPOUNDS FOR MODULATING SYK ACTIVITY AND E3 UBIQUITIN LIGASE ACTIVITY” and filed on November 11, 2022, the disclosure of which is hereby incorporated herein by reference in its entirety. BACKGROUND Field [0002] The present disclosure relates to compounds and to their use in the treatment of various diseases, including cancer and inflammatory conditions. The disclosure also relates to methods for preparation of the compounds and to pharmaceutical compositions comprising such compounds. Background [0003] Protein kinases, the largest family of human enzymes, encompass well over 500 proteins. Spleen Tyrosine Kinase (SYK) is a member of the SYK family of tyrosine kinases and is a regulator of early B-cell development as well as mature B-cell activation, signaling, and survival. [0004] The inhibition of SYK activity can be useful for the treatment of allergic disorders, autoimmune diseases and inflammatory diseases such as: SLE, rheumatoid arthritis, multiple vasculitides, idiopathic thrombocytopenic purpura (ITP), myasthenia gravis, allergic rhinitis, chronic obstructive pulmonary disease (COPD), adult respiratory distress syndrome (ARDs) and asthma. In addition, SYK has been reported to play an important role in ligand- independent tonic signaling through the B-cell receptor, known to be an important survival signal in B-cells. Thus, inhibition of SYK activity may also be useful in treating certain types of cancer, including B-cell lymphoma and leukemia. U.S. Patent Numbers 8,455,493 and 8,440,667 disclose SYK inhibitors, the disclosures of which are hereby incorporated by reference in their entirety. [0005] There is a continued need to provide compounds that are effective for treating diseases mediated by SYK, including compounds having desirable pharmacokinetic properties for use as therapeutics for treating cancers and other diseases. SUMMARY [0006] In some embodiments, provided herein is a compound of formula (I): X – L – Y (I) wherein: X is an E3 ubiquitin ligase binding ligand; L is a linking group covalently bound to both X and Y; and Y is a spleen tyrosine kinase (SYK) binding ligand derived by removal of a hydrogen atom from a compound of formula (II): or a pharmaceutically acceptable salt thereof; wherein R ₁ is phenyl substituted with one or more groups chosen from: halo, hydroxy, carboxy, cyano, C3-C7 cycloalkyl optionally substituted with one or more groups chosen from hydroxy, C ₁ -C ₆ alkoxy, and C ₁ -C ₆ alkyl, C ₂ -C ₇ cycloalkoxy optionally substituted with one or two groups chosen from hydroxy, C ₁ -C ₆ alkoxy, and C ₁ -C ₆ alkyl, 4- to 10- membered heterocycloalkyl optionally substituted with one or two groups chosen from acyl, halo, optionally substituted amino, hydroxy, C ₁ -C ₆ alkoxy, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkyl substituted with hydroxy, C ₁ -C ₆ alkyl substituted with C ₁ -C ₆ alkoxy, C ₁ -C ₆ alkyl substituted with one, two, or three halo groups, optionally substituted amino, optionally substituted 4- to 10- membered heterocycloalkyl, and oxo, 5- to 10- membered heteroaryl, amino optionally substituted with one or two groups chosen from C ₁ -C ₆ alkyl, C1- C ₆ alkyl substituted with halo, C ₁ -C ₆ alkyl substituted with hydroxy, and C ₁ -C ₆ alkyl substituted with C ₁ -C ₆ alkoxy, -C(O)NR ₆ R ₇ , -S(O)2NR ₆ R ₇ , C ₁ -C ₆ alkoxy optionally substituted with one or two groups chosen from hydroxy, C ₁ -C ₆ alkoxy, aminocarbonyl, amino, C-carboxy, O-carboxy, and 4- to 10- membered heterocycloalkyl, (5- to 10- membered heteroaryl)oxy, and C ₁ -C ₆ alkyl optionally substituted with one or two groups chosen from hydroxy, C ₁ -C ₆ alkoxy, halo, trifluoromethyl, optionally substituted amino, and 4- to 10- membered heterocycloalkyl optionally substituted with C ₁ -C ₆ alkyl; or R ₁ is wherein A is chosen from optionally substituted C ₆ -C ₁₀ aryl, optionally substituted 5- to 7-membered cycloalkyl, and optionally substituted 5- to 7-membered heterocycloalkyl; R ₂ is selected from optionally substituted C ₆ -C ₁₀ aryl and optionally substituted 5- to 10- membered heteroaryl; R ₃ is selected from hydrogen, C ₁ -C ₆ alkyl, and halo; R ₄ is selected from hydrogen and C ₁ -C ₆ alkyl; R ₅ is hydrogen; and R ₆ and R ₇ are independently selected from hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkyl substituted with hydroxy, C ₁ -C ₆ alkyl substituted with optionally substituted amino, C ₃ -C ₇ cycloalkyl, C6-C10 aryl, 5- to 10- membered heteroaryl, and 4- to 10- membered heterocycloalkyl, or R ₆ and R ₇ together with the nitrogen to which they are bound form a 3- to 7-membered heterocycloalkyl ring optionally substituted with one or two groups chosen from hydroxy, C ₁ -C ₆ alkyl, and C ₁ -C ₆ alkyl substituted with hydroxy. [0007] In some embodiments, Y is covalently attached to L through R ₁ . [0008] In some embodiments, R1 is phenyl substituted with 4- to 10- membered heterocycloalkyl. In some embodiments, wherein R1 is phenyl substituted with piperazine. In other embodiments, R ₁ is phenyl substituted with amino optionally substituted with C ₁ -C ₆ alkyl. In some embodiments, R ₁ is phenyl substituted with one methylamino group. In some embodiments, R ₁ is selected from the group consisting of: . [0009] In some embodiments, R ₂ is an optionally substituted 5- to 10- membered heteroaryl. In some specific embodiments, R ₂ is an optionally substituted pyrazine. In other specific embodiments, R ₂ is pyrazine substituted with amino. In yet other specific embodiments, R ₂ is In some embodiments, R ₂ . [0010] In some embodiments, R3 is hydrogen. [0011] In some embodiments, R ₄ is hydrogen.

[0012] In some embodiments, Y has a structure selected from the group consisting of:

[0013] In some embodiments, X is a cereblon (CRBN) binding ligand. In some embodiments, X has a structure derived by removal of a hydrogen atom from a structure selected from the group consisting of: and

. In some specific embodiments, X has a structure selected from: [0014] In some embodiments, X is a Von-Hippel-Lindau (VHL) binding ligand. In some specific embodiments, X has a structure selected from: [0015] In some embodiments, L has a structure of formula (III): wherein: R ₈ is single bond or has a structure selected from the group consisting of: R ₉ is single bond or has a structure selected from the group consisting of: a is an integer from 0 to 3; b is an integer from 0 to 4; c is an integer from 0 to 12; d is 0 or 1; and e is an integer from 0 to 3. [0016] In some embodiments, b is 0, d is 0, and c is an integer from 1 to 12. In some such embodiments, c is an integer from 6 to 8. In other such embodiments, c is 7. In yet other embodiments, c is 12. [0017] In some embodiments, a is 0 and c is 0. In some such embodiments, b is 3 or 4. [0018] In some embodiments, d is 1. [0019] In some embodiments, the compound of Formula (I) has a structure provided herein. [0020] In some embodiments, provided herein is a pharmaceutical composition comprising a compound of formula (I) and a pharmaceutically acceptable excipient. [0021] Also provided herein is a method for treating a disease or condition selected from the group consisting of an inflammatory disorder, an allergic disorder, an autoimmune disease, and a cancer in a subject in need thereof, comprising administering a therapeutically effective amount of the compound of formula (I) to the subject. [0022] In some embodiments, the disease or condition is a cancer selected from the group consisting of a hematologic malignancy and a solid tumor. In some embodiments, the disease or condition is a hematologic malignancy selected from the group consisting of lymphoma, multiple myeloma, or leukemia. In some specific embodiments, the disease or condition is selected from the group consisting of small lymphocytic lymphoma, non-Hodgkin’s lymphoma, indolent non-Hodgkin’s lymphoma, refractory iNHL, mantle cell lymphoma, follicular lymphoma, lymphoplasmacytic lymphoma, marginal zone lymphoma, immunoblastic large cell lymphoma, lymphoblastic lymphoma, Splenic marginal zone B-cell lymphoma (+/- villous lymphocytes), Nodal marginal zone lymphoma (+/- monocytoid B-cells), Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type, cutaneous T-cell lymphoma, extranodal T- cell lymphoma, anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, mycosis fungoides, B-cell lymphoma, diffuse large B-cell lymphoma, Mediastinal large B-cell lymphoma, Intravascular large B-cell lymphoma, Primary effusion lymphoma, small non-cleaved cell lymphoma, Burkitt’s lymphoma, multiple myeloma, plasmacytoma, acute lymphocytic leukemia, T-cell acute lymphoblastic leukemia, B-cell acute lymphoblastic leukemia, B-cell prolymphocytic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, juvenile myelomonocytic leukemia, minimal residual disease, hairy cell leukemia, primary myelofibrosis, secondary myelofibrosis, chronic myeloid leukemia, myelodysplastic syndrome, myeloproliferative disease, and Waldestrom’s macroglobulinemia. [0023] In other embodiments, the disease or condition is a solid tumor, wherein the solid tumor is from a cancer selected from the group consisting of pancreatic cancer, urological cancer, bladder cancer, colorectal cancer, colon cancer, breast cancer, prostate cancer, renal cancer, hepatocellular cancer, thyroid cancer, gall bladder cancer, lung cancer (e.g. non-small cell lung cancer, small-cell lung cancer), ovarian cancer, cervical cancer, gastric cancer, endometrial cancer, esophageal cancer, head and neck cancer, melanoma, neuroendocrine cancer, CNS cancer, brain tumors (e.g., glioma, anaplastic oligodendroglioma, adult glioblastoma multiforme, and adult anaplastic astrocytoma), bone cancer, soft tissue sarcoma, retinoblastomas, neuroblastomas, peritoneal effusions, malignant pleural effusions, mesotheliomas, Wilms tumors, trophoblastic neoplasms, hemangiopericytomas, Kaposi’s sarcomas, myxoid carcinoma, round cell carcinoma, squamous cell carcinomas, esophageal squamous cell carcinomas, oral carcinomas, cancers of the adrenal cortex, and ACTH-producing tumors. [0024] In some embodiments, the disease or condition is selected from the group consisting of systemic lupus erythematosus, myestenia gravis, Goodpasture’s syndrome, glomerulonephritis, hemorrhage, pulmonary hemorrhage, atherosclerosis, rheumatoid arthritis, psoriatic arthritis, monoarticular arthritis, osteoarthritis, gouty arthritis, spondylitis, Behçet disease, autoimmune thyroiditis, Reynaud’s syndrome, acute disseminated encephalomyelitis, chronic idiopathic thrombocytopenic purpura, multiple sclerosis, Sjögren’s syndrome, autoimmune hemolytic anemia, tissue graft rejection, hyperacute rejection of transplanted organs, allograft rejection, graft-versus-host disease, diseases involving leukocyte diapedesis, disease states due to leukocyte dyscrasia and metastasis, granulocyte transfusion-associated syndromes, cytokine-induced toxicity, scleroderma, vasculitis, asthma, psoriasis, chronic inflammatory bowel disease, ulcerative colitis, Crohn’s disease, necrotizing enterocolitis, irritable bowel syndrome, dermatomyositis, Addison’s disease, Parkinson’s disease, Alzheimer’s disease, diabetes, type I diabetes mellitus, sepsis, septic shock, endotoxic shock, gram negative sepsis, gram positive sepsis, and toxic shock syndrome, multiple organ injury syndrome secondary to septicemia, trauma, hypovolemic shock, allergic conjunctivitis, vernal conjunctivitis, and thyroid-associated ophthalmopathy, eosinophilic granuloma, eczema, chronic bronchitis, acute respiratory distress syndrome, allergic rhinitis, coryza, hay fever, bronchial asthma, silicosis, pulmonary sarcoidosis, pleurisy, alveolitis, emphysema, pneumonia, bacterial pneumonia, bronchiectasis, and pulmonary oxygen toxicity, reperfusion injury of the myocardium, brain, or extremities, thermal injury, cystic fibrosis, keloid formation or scar tissue formation, fever and myalgias due to infection, and brain or spinal cord injury due to minor trauma, diseases involving leukocyte diapedesis, acute hypersensitivity, delayed hypersensitivity, urticaria, food allergies, skin sunburn, inflammatory pelvic disease, urethritis, uveitis, sinusitis, pneumonitis, encephalitis, meningitis, myocarditis, nephritis, osteomyelitis, myositis, hepatitis, alcoholic hepatitis, gastritis, enteritis, contact dermatitis, atopic dermatitis, gingivitis, appendicitis, pancreatitis, cholocystitis, polycythemia vera, essential thrombocythemia, and polycystic kidney disease. [0025] In some embodiments, the disease or condition is selected from the group consisting of systemic lupus erythematosus, myestenia gravis, rheumatoid arthritis, acute disseminated encephalomyelitis, idiopathic thrombocytopenic purpura, multiple sclerosis, Sjoegren’s syndrome, psoriasis, autoimmune hemolytic anemia, asthma, ulcerative colitis, Crohn’s disease, irritable bowel disease, and chronic obstructive pulmonary disease. systemic lupus erythematosus, myestenia gravis, rheumatoid arthritis, acute disseminated encephalomyelitis, idiopathic thrombocytopenic purpura, multiple sclerosis, Sjoegren’s syndrome, psoriasis, autoimmune hemolytic anemia, asthma, ulcerative colitis, Crohn’s disease, irritable bowel disease, and chronic obstructive pulmonary disease. In some specific embodiments, the disease or condition is selected from the group consisting of asthma, rheumatoid arthritis, multiple sclerosis, chronic obstructive pulmonary disease, and systemic lupus erythematosus. DETAILED DESCRIPTION [0026] Provided are heterobifunctional degrader compounds that bind with spleen tyrosine kinase (SYK) and E3 ubiquitin ligase. Also provided are methods of treating a subject for a SYK-mediated disease by administering a therapeutically effective dose of a pharmaceutical composition including the heterobifunctional degrader. [0027] Before the present invention is described in greater detail, it is to be understood that this invention is not limited to particular embodiments described, as such may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present invention will be limited only by the appended claims. [0028] Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limits of that range is also specifically disclosed. Each smaller range between any stated value or intervening value in a stated range and any other stated or intervening value in that stated range is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included or excluded in the range, and each range where either, neither or both limits are included in the smaller ranges is also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the invention. [0029] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, some potential and exemplary methods and materials may now be described. Any and all publications mentioned herein are incorporated herein by reference to disclose and describe the methods and/or materials in connection with which the publications are cited. It is understood that the present disclosure supersedes any disclosure of an incorporated publication to the extent there is a contradiction. [0030] It must be noted that as used herein and in the appended claims, the singular forms “a”, “an”, and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a droplet” includes a plurality of such droplets and reference to “the discrete entity” includes reference to one or more discrete entities, and so forth. [0031] It is further noted that the claims may be drafted to exclude any element, e.g., any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as “solely”, “only” and the like in connection with the recitation of claim elements, or the use of a “negative” limitation. [0032] The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Further, the dates of publication provided may be different from the actual publication dates which may need to be independently confirmed. To the extent the definition or usage of any term herein conflicts with a definition or usage of a term in an application or reference incorporated by reference herein, the instant application shall control. [0033] As will be apparent to those of skill in the art upon reading this disclosure, each of the individual embodiments described and illustrated herein has discrete components and features which may be readily separated from or combined with the features of any of the other several embodiments without departing from the scope or spirit of the present invention. Any recited method can be carried out in the order of events recited or in any other order which is logically possible. Definitions [0034] “Linker” and “linking group” are used interchangeably to refer to a group that connects to two groups. Exemplary types of connections include covalent bonds. As used herein, the term “radical”, such as in “monoradical” or “diradical”, refers to the number groups that a group can connect with. For instance, a monoradical group can connect to only a single other group, e.g., the methyl (-CH ₃ ) and ethyl (-CH ₂ CH ₃ ) groups are monoradical groups. In contrast, the -CH ₂ - and -CH ₂ CH ₂ - groups are diradical groups since they can each connect to two different groups. Since a linker connects two groups, a linker is a diradical group. Connections between groups can also be described by the term “valent”, such as in “monovalent” or “divalent”, which refers to the bond order of the connection. For instance, the group -CH ₃ is a monovalent group since it can form a single covalent bond with another group, e.g., with -OH to form H ₃ COH. The group =CH ₂ is a divalent group since it can form a double bond with another group, e.g., with an oxygen atom to form formaldehyde (CH ₂ O). [0035] “Alkyl” refers to monovalent saturated aliphatic hydrocarbyl groups having from 1 to 10 carbon atoms and such as 1 to 6 carbon atoms, or 1 to 5, or 1 to 4, or 1 to 3 carbon atoms. This term includes, by way of example, linear and branched hydrocarbyl groups such as methyl (CH ₃ -), ethyl (CH ₃ CH ₂ -), n-propyl (CH ₃ CH ₂ CH ₂ -), isopropyl ((CH ₃ ) ₂ CH-), n-butyl (CH ₃ CH ₂ CH ₂ CH ₂ -), isobutyl ((CH ₃ ) ₂ CHCH ₂ -), sec-butyl ((CH ₃ )(CH ₃ CH ₂ )CH-), t-butyl ((CH ₃ )3C-), n-pentyl (CH ₃ CH ₂ CH ₂ CH ₂ CH ₂ -), and neopentyl ((CH ₃ )3CCH ₂ -). [0036] “Alkylene” refers to divalent aliphatic hydrocarbyl groups preferably having from 1 to 12 and more preferably 1 to 3 carbon atoms that are either straight-chained or branched. This term includes, by way of example, methylene (-CH ₂ -), ethylene (-CH ₂ CH ₂ -), n-propylene (-CH ₂ CH ₂ CH ₂ -), iso-propylene (-CH ₂ CH(CH ₃ )-), (-C(CH ₃ ) ₂ CH ₂ CH ₂ -), (-CH(CH ₃ )CH ₂ -), and the like. [0037] “Substituted alkylene” refers to an alkylene group having from 1 to 3 hydrogens replaced with substituents as described for carbons in the definition of “substituted” below. [0038] “Alkenyl” refers to straight chain or branched hydrocarbyl groups having from 2 to 6 carbon atoms and preferably 2 to 4 carbon atoms and having at least 1 and preferably from 1 to 2 sites of double bond unsaturation. This term includes, by way of example, bi-vinyl, allyl, and but-3-en-1-yl. Included within this term are the cis and trans isomers or mixtures of these isomers. [0039] The term “substituted alkenyl” refers to an alkenyl group as defined herein having from 1 to 5 substituents, or from 1 to 3 substituents, selected from alkoxy, substituted alkoxy, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, acyl, acylamino, acyloxy, amino, substituted amino, aminoacyl, aminoacyloxy, oxyaminoacyl, azido, cyano, halogen, hydroxyl, oxo, thioketo, carboxyl, carboxylalkyl, thioaryloxy, thioheteroaryloxy, thioheterocyclooxy, thiol, thioalkoxy, substituted thioalkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy, heterocyclyl, heterocyclooxy, hydroxyamino, alkoxyamino, nitro, -SO-alkyl, -SO- substituted alkyl, -SO-aryl, -SO-heteroaryl, -SO ₂ -alkyl, -SO ₂ -substituted alkyl, -SO ₂ -aryl and - SO ₂ -heteroaryl. [0040] “Alkynyl” refers to straight or branched monovalent hydrocarbyl groups having from 2 to 6 carbon atoms and preferably 2 to 3 carbon atoms and having at least 1 and preferably from 1 to 2 sites of triple bond unsaturation. Examples of such alkynyl groups include acetylenyl (-C≡CH), and propargyl (-CH ₂ C≡CH). [0041] The term “substituted alkynyl” refers to an alkynyl group as defined herein having from 1 to 5 substituents, or from 1 to 3 substituents, selected from alkoxy, substituted alkoxy, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, acyl, acylamino, acyloxy, amino, substituted amino, aminoacyl, aminoacyloxy, oxyaminoacyl, azido, cyano, halogen, hydroxyl, oxo, thioketo, carboxyl, carboxylalkyl, thioaryloxy, thioheteroaryloxy, thioheterocyclooxy, thiol, thioalkoxy, substituted thioalkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy, heterocyclyl, heterocyclooxy, hydroxyamino, alkoxyamino, nitro, -SO-alkyl, -SO- substituted alkyl, -SO-aryl, -SO-heteroaryl, -SO ₂ -alkyl, -SO ₂ -substituted alkyl, -SO ₂ -aryl, and - SO ₂ -heteroaryl. [0042] “Aryl” or “Ar” refers to a monovalent aromatic carbocyclic group of from 6 to 18 carbon atoms having a single ring (such as is present in a phenyl group) or a ring system having multiple condensed rings (examples of such aromatic ring systems include naphthyl, anthryl and indanyl) which condensed rings may or may not be aromatic, provided that the point of attachment is through an atom of an aromatic ring. This term includes, by way of example, phenyl and naphthyl. Unless otherwise constrained by the definition for the aryl substituent, such aryl groups can optionally be substituted with from 1 to 5 substituents, or from 1 to 3 substituents, selected from acyloxy, hydroxy, thiol, acyl, alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, substituted alkyl, substituted alkoxy, substituted alkenyl, substituted alkynyl, substituted cycloalkyl, substituted cycloalkenyl, amino, substituted amino, aminoacyl, acylamino, alkaryl, aryl, aryloxy, azido, carboxyl, carboxylalkyl, cyano, halogen, nitro, heteroaryl, heteroaryloxy, heterocyclyl, heterocyclooxy, aminoacyloxy, oxyacylamino, thioalkoxy, substituted thioalkoxy, thioaryloxy, thioheteroaryloxy, -SO-alkyl, -SO-substituted alkyl, -SO-aryl, -SO-heteroaryl, -SO ₂ - alkyl, -SO ₂ -substituted alkyl, -SO ₂ -aryl, -SO ₂ -heteroaryl and trihalomethyl. [0043] “Amino” refers to a “-NRARB” group in which RA and RB are each independently selected from hydrogen, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-7 cycloalkyl, C _6-10 aryl, 5-10 membered heteroaryl, and 3-10 membered heterocyclyl, as defined herein. A non- limiting example includes free amino (i.e., -NH2). [0044] “Aminocarbonyl” refers to a “-(C=O)NRARB” group in which RA and RB are as defined above in the “amino” definition. [0045] “O-carboxy” refers to a “-OC(=O)R” group in which R is selected from hydrogen, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-7 carbocyclyl, C _6-10 aryl, 5-10 membered heteroaryl, and 3-10 membered heterocyclyl, as defined herein. [0046] “C-carboxy” refers to a “-C(=O)OR” group in which R is selected from hydrogen, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-7 carbocyclyl, C _6-10 aryl, 5-10 membered heteroaryl, and 3-10 membered heterocyclyl, as defined herein. A non-limiting example includes carboxyl (i.e., -C(=O)OH). [0047] “Cyano” or “nitrile” refers to the group –CN. [0048] “Cycloalkyl” refers to cyclic alkyl groups of from 3 to 10 carbon atoms having single or multiple cyclic rings including fused, bridged, and spiro ring systems. Examples of suitable cycloalkyl groups include, for instance, adamantyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclooctyl and the like. Such cycloalkyl groups include, by way of example, single ring structures such as cyclopropyl, cyclobutyl, cyclopentyl, cyclooctyl, and the like, or multiple ring structures such as adamantanyl, and the like. [0049] The term “substituted cycloalkyl” refers to cycloalkyl groups having from 1 to 5 substituents, or from 1 to 3 substituents, selected from alkyl, substituted alkyl, alkoxy, substituted alkoxy, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, acyl, acylamino, acyloxy, amino, substituted amino, aminoacyl, aminoacyloxy, oxyaminoacyl, azido, cyano, halogen, hydroxyl, oxo, thioketo, carboxyl, carboxylalkyl, thioaryloxy, thioheteroaryloxy, thioheterocyclooxy, thiol, thioalkoxy, substituted thioalkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy, heterocyclyl, heterocyclooxy, hydroxyamino, alkoxyamino, nitro, -SO-alkyl, -SO- substituted alkyl, -SO-aryl, -SO-heteroaryl, -SO ₂ -alkyl, -SO ₂ -substituted alkyl, -SO ₂ -aryl and - SO ₂ -heteroaryl. [0050] “Cycloalkenyl” refers to non-aromatic cyclic alkyl groups of from 3 to 10 carbon atoms having single or multiple rings and having at least one double bond and preferably from 1 to 2 double bonds. [0051] The term “substituted cycloalkenyl” refers to cycloalkenyl groups having from 1 to 5 substituents, or from 1 to 3 substituents, selected from alkoxy, substituted alkoxy, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, acyl, acylamino, acyloxy, amino, substituted amino, aminoacyl, aminoacyloxy, oxyaminoacyl, azido, cyano, halogen, hydroxyl, keto, thioketo, carboxyl, carboxylalkyl, thioaryloxy, thioheteroaryloxy, thioheterocyclooxy, thiol, thioalkoxy, substituted thioalkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy, heterocyclyl, heterocyclooxy, hydroxyamino, alkoxyamino, nitro, -SO-alkyl, -SO-substituted alkyl, -SO-aryl, - SO-heteroaryl, -SO ₂ -alkyl, -SO ₂ -substituted alkyl, -SO ₂ -aryl and -SO ₂ -heteroaryl. [0052] “Cycloalkynyl” refers to non-aromatic cycloalkyl groups having single or multiple rings and having at least one triple bond. [0053] “Halo” or “halogen” refers to fluoro, chloro, bromo, and iodo. [0054] “Heteroaryl” refers to an aromatic group of from 1 to 15 carbon atoms, such as from 1 to 10 carbon atoms and 1 to 10 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur within the ring. Such heteroaryl groups can have a single ring (such as, pyridinyl, imidazolyl or furyl) or multiple condensed rings in a ring system (for example as in groups such as, indolizinyl, quinolinyl, benzofuran, benzimidazolyl or benzothienyl), wherein at least one ring within the ring system is aromatic. To satisfy valence requirements, any heteroatoms in such heteroaryl rings may or may not be bonded to H or a substituent group, e.g., an alkyl group or other substituent as described herein. In certain embodiments, the nitrogen and/or sulfur ring atom(s) of the heteroaryl group are optionally oxidized to provide for the N-oxide (N→O), sulfinyl, or sulfonyl moieties. This term includes, by way of example, pyridinyl, pyrrolyl, indolyl, thiophenyl, and furanyl. Unless otherwise constrained by the definition for the heteroaryl substituent, such heteroaryl groups can be optionally substituted with 1 to 5 substituents, or from 1 to 3 substituents, selected from acyloxy, hydroxy, thiol, acyl, alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, substituted alkyl, substituted alkoxy, substituted alkenyl, substituted alkynyl, substituted cycloalkyl, substituted cycloalkenyl, amino, substituted amino, aminoacyl, acylamino, alkaryl, aryl, aryloxy, azido, carboxyl, carboxylalkyl, cyano, halogen, nitro, heteroaryl, heteroaryloxy, heterocyclyl, heterocyclooxy, aminoacyloxy, oxyacylamino, thioalkoxy, substituted thioalkoxy, thioaryloxy, thioheteroaryloxy, -SO-alkyl, -SO-substituted alkyl, -SO- aryl, -SO-heteroaryl, -SO ₂ -alkyl, -SO ₂ -substituted alkyl, -SO ₂ -aryl and -SO ₂ -heteroaryl, and trihalomethyl. [0055] “Heterocycle,” “heterocyclic,” “heterocycloalkyl,” and “heterocyclyl” refer to a saturated or unsaturated group having a single ring or multiple condensed rings, including fused bridged and spiro ring systems, and having from 3 to 20 ring atoms, including 1 to 10 hetero atoms. These ring atoms are selected from nitrogen, sulfur, or oxygen, where, in fused ring systems, one or more of the rings can be cycloalkyl, aryl, or heteroaryl, provided that the point of attachment is through the non-aromatic ring. In certain embodiments, the nitrogen and/or sulfur atom(s) of the heterocyclic group are optionally oxidized to provide for the N-oxide, -S(O)-, or –SO ₂ - moieties. To satisfy valence requirements, any heteroatoms in such heterocyclic rings may or may not be bonded to one or more H or one or more substituent group(s), e.g., an alkyl group or other substituent as described herein. [0056] Examples of heterocycles and heteroaryls include, but are not limited to, azetidine, pyrrole, imidazole, pyrazole, pyridine, pyrazine, pyrimidine, pyridazine, indolizine, isoindole, indole, dihydroindole, indazole, purine, quinolizine, isoquinoline, quinoline, phthalazine, naphthylpyridine, quinoxaline, quinazoline, cinnoline, pteridine, carbazole, carboline, phenanthridine, acridine, phenanthroline, isothiazole, phenazine, isoxazole, phenoxazine, phenothiazine, imidazolidine, imidazoline, piperidine, piperazine, indoline, phthalimide, 1,2,3,4- tetrahydroisoquinoline, 4,5,6,7-tetrahydrobenzo[b]thiophene, thiazole, thiazolidine, thiophene, benzo[b]thiophene, morpholinyl, thiomorpholinyl (also referred to as thiamorpholinyl), 1,1- dioxothiomorpholinyl, piperidinyl, pyrrolidine, tetrahydrofuranyl, and the like. [0057] Unless otherwise constrained by the definition for the heterocyclic substituent, such heterocyclic groups can be optionally substituted with 1 to 5, or from 1 to 3 substituents, selected from alkoxy, substituted alkoxy, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, acyl, acylamino, acyloxy, amino, substituted amino, aminoacyl, aminoacyloxy, oxyaminoacyl, azido, cyano, halogen, hydroxyl, oxo, thioketo, carboxyl, carboxylalkyl, thioaryloxy, thioheteroaryloxy, thioheterocyclooxy, thiol, thioalkoxy, substituted thioalkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy, heterocyclyl, heterocyclooxy, hydroxyamino, alkoxyamino, nitro, -SO-alkyl, -SO-substituted alkyl, -SO-aryl, -SO-heteroaryl, -SO ₂ -alkyl, -SO ₂ - substituted alkyl, -SO ₂ -aryl, -SO ₂ -heteroaryl, and fused heterocycle. [0058] “Oxo” refers to the atom (=O). [0059] In addition to the disclosure herein, the term “substituted,” when used to modify a specified group or radical, can also mean that one or more hydrogen atoms of the specified group or radical are each, independently of one another, replaced with the same or different substituent groups as defined below. [0060] In addition to the groups disclosed with respect to the individual terms herein, substituent groups for substituting for one or more hydrogens (any two hydrogens on a single carbon can be replaced with =O, =NR ⁷⁰ , =N-OR ⁷⁰ , =N ₂ or =S) on saturated carbon atoms in the specified group or radical are, unless otherwise specified, -R ⁶⁰ , halo, =O, -OR ⁷⁰ , -SR ⁷⁰ , -NR ⁸⁰ R ⁸⁰ , trihalomethyl, -CN, -OCN, -SCN, -NO, -NO2, =N2, -N3, -SO ₂ R ⁷⁰ , -SO ₂ O ^– M ⁺ , -SO ₂ OR ⁷⁰ , -OSO ₂ R ⁷⁰ , -OSO ₂ O ^– M ⁺ , -OSO ₂ OR ⁷⁰ , -P(O)(O ^– ) ₂ (M ⁺ ) ₂ , -P(O)(OR ⁷⁰ )O ^– M ⁺ , -P(O)(OR ⁷⁰ ) 2, -C(O)R ⁷⁰ , -C(S)R ⁷⁰ , -C(NR ⁷⁰ )R ⁷⁰ , -C(O)O ^– M ⁺ , -C(O)OR ⁷⁰ , -C(S)OR ⁷⁰ , -C(O)NR ⁸⁰ R ⁸⁰ , -C(NR ⁷⁰ )NR ⁸⁰ R ⁸⁰ , -OC(O)R ⁷⁰ , -OC(S)R ⁷⁰ , -OC(O)O -M ⁺ , -OC(O)OR ⁷⁰ , -OC(S)OR ⁷⁰ , -NR ⁷⁰ C(O)R ⁷⁰ , -NR ⁷⁰ C(S)R ⁷⁰ , -NR ⁷⁰ CO ₂ ^– M ⁺ , -NR ⁷⁰ CO2R ⁷⁰ , -NR ⁷⁰ C(S)OR ⁷⁰ , -NR ⁷⁰ C(O)NR ⁸⁰ R ⁸⁰ , -NR ⁷⁰ C(NR ⁷⁰ )R ⁷⁰ and -NR ⁷⁰ C(NR ⁷⁰ )NR ⁸⁰ R ⁸⁰ , where R ⁶⁰ is selected from the group consisting of alkyl, cycloalkyl, heteroalkyl, heterocycloalkylalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl and heteroarylalkyl, each optionally substituted with one or more halo, hydroxy, cyano, haloalkyl, or alkoxy, each R ⁷⁰ is independently hydrogen or R ⁶⁰ ; each R ⁸⁰ is independently R ⁷⁰ or alternatively, two R ^80’ s, taken together with the nitrogen atom to which they are bonded, form a 5-, 6- or 7-membered heterocycloalkyl which may optionally include from 1 to 4 of the same or different additional heteroatoms selected from the group consisting of O, N and S, of which N may have -H or C1-C3 alkyl substitution; and each M ⁺ is a counter ion with a net single positive charge. Each M ⁺ may independently be, for example, an alkali ion, such as K ⁺ , Na ⁺ , Li ⁺ ; an ammonium ion, such as ⁺ N(R ⁶⁰ )4; or an alkaline earth ion, such as [Ca ²⁺ ]0.5, [Mg ²⁺ ]0.5, or [Ba ²⁺ ]0.5 (“subscript 0.5 means that one of the counter ions for such divalent alkali earth ions can be an ionized form of a compound of the invention and the other a typical counter ion such as chloride, or two ionized compounds disclosed herein can serve as counter ions for such divalent alkali earth ions, or a doubly ionized compound of the invention can serve as the counter ion for such divalent alkali earth ions). As specific examples, -NR ⁸⁰ R ⁸⁰ is meant to include -NH ₂ , -NH-alkyl, N-pyrrolidinyl, N-piperazinyl, 4N-methyl-piperazin-1-yl and N-morpholinyl. [0061] In addition to the disclosure herein, substituent groups for hydrogens on unsaturated carbon atoms in “substituted” alkene, alkyne, aryl and heteroaryl groups are, unless otherwise specified, -R ⁶⁰ , halo, -O-M ⁺ , -OR ⁷⁰ , -SR ⁷⁰ , -S ^– M ⁺ , -NR ⁸⁰ R ⁸⁰ , trihalomethyl, -CF3, -CN, -OCN, -SCN, -NO, -NO2, -N3, -SO ₂ R ⁷⁰ , -SO3 ^– M ⁺ , -SO3R ⁷⁰ , -OSO ₂ R ⁷⁰ , -OSO3 ^– M ⁺ , -OSO3R ⁷⁰ , -PO3 ^-2 (M ⁺ )2, -P(O)(OR ⁷⁰ )O ^– M ⁺ , -P(O)(OR ⁷⁰ ) ₂ , -C(O)R ⁷⁰ , -C(S)R ⁷⁰ , -C(NR ⁷⁰ )R ⁷⁰ , -CO ₂ ^– M ⁺ , -CO2R ⁷⁰ , -C(S)OR ⁷⁰ , -C(O)NR ⁸⁰ R ⁸⁰ , -C(NR ⁷⁰ )NR ⁸⁰ R ⁸⁰ , -OC(O)R ⁷⁰ , -OC(S)R ⁷⁰ , -OCO2 ^– M ⁺ , -OCO2R ⁷⁰ , -OC(S)OR ⁷⁰ , -NR ⁷⁰ C(O)R ⁷⁰ , -NR ⁷⁰ C(S)R ⁷⁰ , -NR ⁷⁰ CO2 ^– M ⁺ , -NR ⁷⁰ CO ₂ R ⁷⁰ , -NR ⁷⁰ C(S)OR ⁷⁰ , -NR ⁷⁰ C(O)NR ⁸⁰ R ⁸⁰ , -NR ⁷⁰ C(NR ⁷⁰ )R ⁷⁰ and -NR ⁷⁰ C(NR ⁷⁰ )NR ⁸⁰ R ⁸⁰ , where R ⁶⁰ , R ⁷⁰ , R ⁸⁰ and M ⁺ are as previously defined, provided that in case of substituted alkene or alkyne, the substituents are not -O-M ⁺ , -OR ⁷⁰ , -SR ⁷⁰ , or -S ^– M ⁺ . [0062] In addition to the groups disclosed with respect to the individual terms herein, substituent groups for hydrogens on nitrogen atoms in “substituted” heteroalkyl and cycloheteroalkyl groups are, unless otherwise specified, -R ⁶⁰ , -O-M ⁺ , -OR ⁷⁰ , -SR ⁷⁰ , -S-M ⁺ , -NR ⁸⁰ R ⁸⁰ , trihalomethyl, -CF3, -CN, -NO, -NO2, -S(O)2R ⁷⁰ , -S(O)2O-M ⁺ , -S(O)2OR ⁷⁰ , -OS(O)2R ⁷⁰ , -OS(O)2 O-M ⁺ , -OS(O)2OR ⁷⁰ , -P(O)(O-)2(M ⁺ )2, -P(O)(OR ⁷⁰ )O-M ⁺ , -P(O)(OR ⁷⁰ )(OR ⁷⁰ ), -C(O)R ⁷⁰ , -C(S)R ⁷ 0, -C(NR ⁷⁰ )R ⁷⁰ , -C(O)OR ⁷⁰ , -C(S)OR ⁷⁰ , -C(O)NR ⁸⁰ R ⁸⁰ , -C(NR ⁷⁰ )NR ⁸⁰ R ⁸⁰ , -OC(O)R ⁷⁰ , -OC(S)R ⁷ 0, -OC(O)OR ⁷⁰ , -OC(S)OR ⁷⁰ , -NR ⁷⁰ C(O)R ⁷⁰ , -NR ⁷⁰ C(S)R ⁷⁰ , -NR ⁷⁰ C(O)OR ⁷⁰ , -NR ⁷⁰ C(S)OR ⁷⁰ , - NR ⁷⁰ C(O)NR ⁸⁰ R ⁸⁰ , -NR ⁷⁰ C(NR ⁷⁰ )R ⁷⁰ and -NR ⁷⁰ C(NR ⁷⁰ )NR ⁸⁰ R ⁸⁰ , where R ⁶⁰ , R ⁷⁰ , R ⁸⁰ and M ⁺ are as previously defined. [0063] In addition to the disclosure herein, in a certain embodiment, a group that is substituted has 1, 2, 3, or 4 substituents, 1, 2, or 3 substituents, 1 or 2 substituents, or 1 substituent. [0064] It is understood that in all substituted groups defined above, polymers arrived at by defining substituents with further substituents to themselves (e.g., substituted aryl having a substituted aryl group as a substituent which is itself substituted with a substituted aryl group, which is further substituted by a substituted aryl group, etc.) are not intended for inclusion herein. In such cases, the maximum number of such substitutions is three. For example, serial substitutions of substituted aryl groups specifically contemplated herein are limited to substituted aryl- (substituted aryl)-substituted aryl. [0065] Unless indicated otherwise, the nomenclature of substituents that are not explicitly defined herein are arrived at by naming the terminal portion of the functionality followed by the adjacent functionality toward the point of attachment. For example, the substituent “arylalkyloxycarbonyl” refers to the group (aryl)-(alkyl)-O-C(O)-. [0066] As to any of the groups disclosed herein which contain one or more substituents, it is understood, of course, that such groups do not contain any substitution or substitution patterns which are sterically impractical and/or synthetically non-feasible. In addition, the subject compounds include all stereochemical isomers arising from the substitution of these compounds. [0067] The term “pharmaceutically acceptable salt” means a salt which is acceptable for administration to a patient, such as a mammal (salts with counterions having acceptable mammalian safety for a given dosage regime). Such salts can be derived from pharmaceutically acceptable inorganic or organic bases and from pharmaceutically acceptable inorganic or organic acids. “Pharmaceutically acceptable salt” refers to pharmaceutically acceptable salts of a compound, which salts are derived from a variety of organic and inorganic counter ions well known in the art and include, by way of example only, sodium, potassium, calcium, magnesium, ammonium, tetraalkylammonium, and the like; and when the molecule contains a basic functionality, salts of organic or inorganic acids, such as hydrochloride, hydrobromide, formate, tartrate, besylate, mesylate, acetate, maleate, oxalate, and the like. [0068] The term “salt thereof” means a compound formed when a proton of an acid is replaced by a cation, such as a metal cation or an organic cation and the like. Where applicable, the salt is a pharmaceutically acceptable salt, although this is not required for salts of intermediate compounds that are not intended for administration to a patient. By way of example, salts of the present compounds include those wherein the compound is protonated by an inorganic or organic acid to form a cation, with the conjugate base of the inorganic or organic acid as the anionic component of the salt. [0069] Compounds disclosed herein include all stereoisomers thereof. “Stereoisomer” and “stereoisomers” refer to compounds that have same atomic connectivity but different atomic arrangement in space. Stereoisomers include cis-trans isomers, E and Z isomers, enantiomers, and diastereomers. [0070] Compounds disclosed herein include all tautomers thereof. “Tautomer” refers to alternate forms of a molecule that differ only in electronic bonding of atoms and/or in the position of a proton, such as enol-keto and imine-enamine tautomers, or the tautomeric forms of heteroaryl groups containing a -N=C(H)-NH- ring atom arrangement, such as pyrazoles, imidazoles, benzimidazoles, triazoles, and tetrazoles. A person of ordinary skill in the art would recognize that other tautomeric ring atom arrangements are possible. [0071] It will be appreciated that the term “or a salt or solvate or stereoisomer thereof” is intended to include all permutations of salts, solvates and stereoisomers, such as a solvate of a pharmaceutically acceptable salt of a stereoisomer of subject compound. Compounds [0072] Provided are heterobifunctional degrader compounds that bind with spleen tyrosine kinase (SYK) and E3 ubiquitin ligases. In some cases, the compound is of formula (I): X – L – Y (I) [0073] wherein: [0074] X is an E3 ubiquitin ligase binding ligand; [0075] L is a linking group covalently bound to both X and Y; and Y is a spleen tyrosine kinase (SYK) binding ligand derived by removal of a hydrogen atom from a compound of formula (II): [0076] or a pharmaceutically acceptable salt thereof. GROUP Y [0077] Y is a spleen tyrosine kinase (SYK) binding ligand of formula (II). The term “binding ligand” means that a group is capable of binding to another group, e.g. group Y is capable of binding to a SYK. [0078] In some embodiments, R ₁ is In some embodiments, R ₂ is . In some embodiments, R ₃ is hydrogen. In some embodiments, R4 is hydrogen. In some embodiments, R5 is hydrogen. [0079] In some cases, Y has a structure selected from the group consisting of:

. [0080] Additional exemplary Y groups are described in U.S. Patent Application Publications 2010/0222323 and 2015/0175616 (hereinafter the ‘323 and ‘616 publications), which are incorporated herein by reference. [0081] The Y group can connect L at any suitable point. For example, a hydrogen atom at any one of the locations marked with the asterisk (*) in the structures below can be removed, thereby providing a location for a covalent bond to L. As such, in some cases the Y group connects to the L group through an aromatic carbon, through an alkyl carbon, or through a nitrogen atom. Group X [0082] As described above, X is an E3 ubiquitin ligase binding ligand. In other words, it has the ability to bind to an E3 ubiquitin ligase. This binding, and its potential use in treating a patient for a medical condition, can be understood by considering the role of the E3 ubiquitin ligase in the biochemical process known as the Ubiquitin Proteasome System (UPS). [0083] The Ubiquitin Proteasome System (UPS) helps to regulate protein homoeostasis by degrading proteins, e.g. proteins that are damaged or misfolded. The UPS system involves a sequence of enzymatic events that are referred to as E1, E2, and E3. During the E1 step, the protein ubiquitin is activated such that it forms a covalent intermediate with the E1 enzyme. Next, the ubiquitin protein is transferred from the E1 enzyme to the E2 enzyme (i.e., the E2 ubiquitin-conjugating enzyme). In the final step, the E3 enzyme (i.e., the E3 ubiquitin ligase) catalyzes the transfer of the ubiquitin from E2 to the protein that is destined for degradation. Afterwards, the presence of the ubiquitin, or a polyubiquitin chain, on the target protein is recognized by a separate element called proteosomes, which actually degrade the target protein. As such, the term “E3 ubiquitin ligase” refers to an enzyme that catalyze the transfer of a ubiquitin group from another enzyme, e.g. the E2 ubiquitin-conjugating enzyme, to a target protein, e.g. wherein the target protein is degraded by a proteasome upon detection of one or more ubiquitin groups. [0084] As such, since the X group of the present compounds is capable of binding to a part of the E3 ubiquitin ligase, this binding allows the compounds to influence the action Ubiquitin Ligase System in some cases, such as using the UPS to selectively degrade certain proteins, which can be used in medical treatment of a patient. [0085] In some cases, X is a cereblon (CRBN) binding ligand, wherein CRBN is a protein encoded by the CRBN gene. Additional names for CRBN include MRT2 and MRT2A (Mental Retardation, Non-Syndromic, Autosomal Recessive, A2). The role of CRBN in the UPS degradation of proteins occurs when CRBN joins other proteins to form the E3 enzyme complex, i.e. the “E3 ubiquitin ligase complex”. In some cases CRBN joins with Cullins-4A (CUL4A), regulator of cullins 1 (ROC1), and damaged DNA binding protein 1 (DDB1) to form the E3 ubiquitin ligase complex. As such, since the X group of the present compounds has the ability to bind to cereblon (CRBN), this interaction can in some cases bring the compounds into proximity with the E3 ubiquitin ligase complex as a whole. In some cases, X binds to a CRBN protein that is encoded by a human CRBN gene located at band 3p26.2 of chromosome 3. [0086] In some cases, X is a CRBN binding ligand that is a small molecule group, e.g. it has 200 atoms or less. For example, X can have a structure derived by removal of a hydrogen atom from a structure selected from the group consisting of:

. [0087] The X group can connect L at any suitable point. For example, a hydrogen atom at any one of the locations marked with the asterisk (*) in the structure below can be removed, thereby providing a location for a covalent bond to L. As such, in some cases the X group connects to the L group through an aryl carbon, through an alkyl carbon, or through a nitrogen atom. [0088] As another example, the X group can be derived from the molecule shown below, e.g., wherein the connection to L can be through the group shown as -NH2. In other cases, the X group has the structure shown below with the exception that a hydrogen atom corresponding to one of those marked with an asterisk (*) in the above example is removed, providing a location for the bond to L. [0089] As such, the X group can have a structure derived from the four CRBN binding ligands shown above, wherein one hydrogen atom is removed, providing a location for covalent binding to L. In some cases, the X group has the formula

[0090] In addition to cereblon (CRBN), Von Hippel-Lindau (VHL) is another protein involved with E3 ubiquitin ligase. The VHL protein is encoded by the VHL gene, and is sometimes also referred to as the “Von Hippel-Lindau tumor suppressor” since mutation in the VHL gene can cause cancerous tumors. In some cases, X binds to a VHL protein encoded by a human VHL gene located at band 3p25.3 of chromosome 3. In relation to the Ubiquitin Proteasome System (UPS), VHL can join with other proteins to form an E3 ubiquitin ligase, e.g. by joining with elongin B, elongin C, and cullin-2. Additional names for the VHL protein include HRCA1, RCA1, and VHL1. Thus, since the VHL protein is part of an E3 ubiquitin ligase, if X is a VHL binding ligand, this binding can bring the compounds described in the present application into proximity with the E3 ubiquitin ligase, potentially allowing for alteration or use of that ligase, such as for medical treatment. [0091] In some cases, X is a Von Hippel-Lindau (VHL) binding ligand. In some cases, X is a VHL binding ligand that is a small molecule group, e.g. it has 200 atoms or less. For instance, X can have the structure derived by removal of a hydrogen atom from a structure shown below. [0092] X can be covalently bonded to L at any suitable location. For instance, a hydrogen atom at any of the locations marked with an asterisk (*) can be removed, providing a location for binding to L. In some cases, X connects to L through an aryl carbon, an alkyl carbon, a nitrogen atom, or an oxygen atom. [0093] For example, X can have a structure selected from: [0094] In some cases, X specifically binds to the E3 ubiquitin ligase. As used herein, “specific binding” refers to the ability of a first group (or a first member of a specific binding pair) to preferentially bind to a particular analyte (or a second member of a specific binding pair) in a mixture of different analytes. For example, Y might preferentially bind to the E3 ubiquitin ligase over another protein in a cell, e.g. tumor necrosis factor alpha (TNF-α). In some cases, the binding preference is 5-fold or more, such as 10-fold or more or 100-fold or more. GROUP L [0095] As described above, L is a linking group that is covalently bonded to X and Y. As used herein, “linking group” is used interchangeably with “linker” to refer to a group that connects to two or more other groups, e.g. X and Y. In some cases, the backbone of the linking group L is 100 or less atoms, such as 50 or less or 25 or less. The term “backbone” refers the smallest number of atoms that connect each of the terminal atoms to one another through a sequence of covalent bonds, wherein the terminal atoms are atoms that are bonded to other groups, e.g. X and Y. In some embodiments, L is a hydrocarbon group, e.g. alkyl, alkylene, alkenylene, alkynylene, aryl, heteroaryl, cycloalkyl, heterocycle, or a substituted derivative thereof, or combinations thereof. In some cases, the linking group L includes a combination of different groups, e.g., a substituted alkyl connected to a heterocycle. [0096] In some cases, L has a structure of formula (III) wherein: R ₈ may be a single bond or have a structure selected from the group consisting of: R ₉ may be a single bond or have a structure selected from the group consisting of: [0097] In some embodiments, a is an integer from 0 to 3; b is an integer from 0 to 4; c is an integer from 0 to 12; d is 0 or 1; and e is an integer from 0 to 3. [0098] In some embodiments, b is 0, d is 0, and c is an integer from 1 to 12 (for example, 6 to 8, 7, or 12) [0099] In some embodiments, a is 0 and c is 0. In some embodiments, a is 0, c is 0, and b is 3 or 4. [0100] In some embodiments, d is 1. [0101] In some cases, L has a structure selected from the linking groups of the compounds discussed in the Specific Embodiments section below. For example, Compound 101 appears in the Specific Embodiments section and is also shown below. [0102] It can be seen that Compound 101 has an X group and Y group that are discussed above. Hence, it can be shown that the middle L group has the structure shown below.

[0103] This analysis can be repeated with each of the compounds of the Specific Embodiments section below and demonstrates several different identities for the L linker. [0104] Any other suitable linking group, i.e. linker, can be used. In some cases, the linking group includes an alkyl chain, aryl chain, or polyethylene glycol chain that is terminated in its two ends with two coupling group each independently selected from an amine, carbamate, carboxylic acid, carboxylate, maleimide, activated ester, N-hydroxysuccinimidyl, hydrazine, hydrazide, hydrazine, azide, alkyne, aldehyde, or thiol. In some cases, the two coupling groups are different from one another, allowing for selective coupling of the first end of the linker to the X group and the selective coupling of the second end of the linker to the Y group. Specific Embodiments [0105] In some cases, the compound has a structure selected from the group consisting of:

Methods [0106] Also provided are methods of treating a subject for a SYK-mediated disease by administering a therapeutically effective dose of a pharmaceutical composition including a heterobifunctional degrader compound as described above. [0107] In some embodiments, the compounds described herein can be used in a method for treating a disease or condition selected from the group consisting of an inflammatory disorder, an allergic disorder, an autoimmune disease, and a cancer in a subject in need thereof. [0108] In some embodiments, the compounds described herein can be used in a method for treating a cancer selected from the group consisting of a hematologic malignancy and a solid tumor. [0109] In some embodiments, the compounds described herein can be used in a method for treating a hematologic malignancy selected from the group consisting of lymphoma, multiple myeloma, or leukemia. [0110] In some embodiments, the compounds described herein can be used in a method for treating a disease or condition selected from the group consisting of small lymphocytic lymphoma, non-Hodgkin’s lymphoma, indolent non-Hodgkin’s lymphoma, refractory iNHL, mantle cell lymphoma, follicular lymphoma, lymphoplasmacytic lymphoma, marginal zone lymphoma, immunoblastic large cell lymphoma, lymphoblastic lymphoma, Splenic marginal zone B-cell lymphoma (+/- villous lymphocytes), Nodal marginal zone lymphoma (+/- monocytoid B-cells), Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type, cutaneous T-cell lymphoma, extranodal T-cell lymphoma, anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, mycosis fungoides, B-cell lymphoma, diffuse large B-cell lymphoma, Mediastinal large B-cell lymphoma, Intravascular large B-cell lymphoma, Primary effusion lymphoma, small non-cleaved cell lymphoma, Burkitt’s lymphoma, multiple myeloma, plasmacytoma, acute lymphocytic leukemia, T-cell acute lymphoblastic leukemia, B-cell acute lymphoblastic leukemia, B-cell prolymphocytic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, juvenile myelomonocytic leukemia, minimal residual disease, hairy cell leukemia, primary myelofibrosis, secondary myelofibrosis, chronic myeloid leukemia, myelodysplastic syndrome, myeloproliferative disease, and Waldestrom’s macroglobulinemia. [0111] In some embodiments, the compounds described herein can be used in a method for treating a solid tumor, wherein the solid tumor is from a cancer selected from the group consisting of pancreatic cancer, urological cancer, bladder cancer, colorectal cancer, colon cancer, breast cancer, prostate cancer, renal cancer, hepatocellular cancer, thyroid cancer, gall bladder cancer, lung cancer (e.g. non-small cell lung cancer, small-cell lung cancer), ovarian cancer, cervical cancer, gastric cancer, endometrial cancer, esophageal cancer, head and neck cancer, melanoma, neuroendocrine cancer, CNS cancer, brain tumors (e.g., glioma, anaplastic oligodendroglioma, adult glioblastoma multiforme, and adult anaplastic astrocytoma), bone cancer, soft tissue sarcoma, retinoblastomas, neuroblastomas, peritoneal effusions, malignant pleural effusions, mesotheliomas, Wilms tumors, trophoblastic neoplasms, hemangiopericytomas, Kaposi’s sarcomas, myxoid carcinoma, round cell carcinoma, squamous cell carcinomas, esophageal squamous cell carcinomas, oral carcinomas, cancers of the adrenal cortex, and ACTH-producing tumors. [0112] In some embodiments, the compounds described herein can be used in a method for treating a disease or condition selected from the group consisting of systemic lupus erythematosus, myestenia gravis, Goodpasture’s syndrome, glomerulonephritis, hemorrhage, pulmonary hemorrhage, atherosclerosis, rheumatoid arthritis, psoriatic arthritis, monoarticular arthritis, osteoarthritis, gouty arthritis, spondylitis, Behçet disease, autoimmune thyroiditis, Reynaud’s syndrome, acute disseminated encephalomyelitis, chronic idiopathic thrombocytopenic purpura, multiple sclerosis, Sjögren’s syndrome, autoimmune hemolytic anemia, tissue graft rejection, hyperacute rejection of transplanted organs, allograft rejection, graft-versus-host disease, diseases involving leukocyte diapedesis, disease states due to leukocyte dyscrasia and metastasis, granulocyte transfusion-associated syndromes, cytokine-induced toxicity, scleroderma, vasculitis, asthma, psoriasis, chronic inflammatory bowel disease, ulcerative colitis, Crohn’s disease, necrotizing enterocolitis, irritable bowel syndrome, dermatomyositis, Addison’s disease, Parkinson’s disease, Alzheimer’s disease, diabetes, type I diabetes mellitus, sepsis, septic shock, endotoxic shock, gram negative sepsis, gram positive sepsis, and toxic shock syndrome, multiple organ injury syndrome secondary to septicemia, trauma, hypovolemic shock, allergic conjunctivitis, vernal conjunctivitis, and thyroid-associated ophthalmopathy, eosinophilic granuloma, eczema, chronic bronchitis, acute respiratory distress syndrome, allergic rhinitis, coryza, hay fever, bronchial asthma, silicosis, pulmonary sarcoidosis, pleurisy, alveolitis, emphysema, pneumonia, bacterial pneumonia, bronchiectasis, and pulmonary oxygen toxicity, reperfusion injury of the myocardium, brain, or extremities, thermal injury, cystic fibrosis, keloid formation or scar tissue formation, fever and myalgias due to infection, and brain or spinal cord injury due to minor trauma, diseases involving leukocyte diapedesis, acute hypersensitivity, delayed hypersensitivity, urticaria, food allergies, skin sunburn, inflammatory pelvic disease, urethritis, uveitis, sinusitis, pneumonitis, encephalitis, meningitis, myocarditis, nephritis, osteomyelitis, myositis, hepatitis, alcoholic hepatitis, gastritis, enteritis, contact dermatitis, atopic dermatitis, gingivitis, appendicitis, pancreatitis, cholocystitis, polycythemia vera, essential thrombocythemia, and polycystic kidney disease. [0113] In some embodiments, the compounds described herein can be used in a method for treating a disease or condition selected from the group consisting of systemic lupus erythematosus, myestenia gravis, rheumatoid arthritis, acute disseminated encephalomyelitis, idiopathic thrombocytopenic purpura, multiple sclerosis, Sjoegren’s syndrome, psoriasis, autoimmune hemolytic anemia, asthma, ulcerative colitis, Crohn’s disease, irritable bowel disease, and chronic obstructive pulmonary disease. systemic lupus erythematosus, myestenia gravis, rheumatoid arthritis, acute disseminated encephalomyelitis, idiopathic thrombocytopenic purpura, multiple sclerosis, Sjoegren’s syndrome, psoriasis, autoimmune hemolytic anemia, asthma, ulcerative colitis, Crohn’s disease, irritable bowel disease, and chronic obstructive pulmonary disease. [0114] In some embodiments, the compounds described herein can be used in a method for treating a disease or condition selected from the group consisting of asthma, rheumatoid arthritis, multiple sclerosis, chronic obstructive pulmonary disease, and systemic lupus erythematosus. [0115] In some embodiments, the compound is a compound described in the Specific Embodiments section above. [0116] The following example schemes are provided for the guidance of the reader, and collectively represent an example method for making the compounds provided herein. Furthermore, other methods for preparing compounds described herein will be readily apparent to the person of ordinary skill in the art in light of the following reaction schemes and examples. Unless otherwise indicated, all variables are as defined above EXAMPLES General procedures [0117] It will be apparent to the skilled artisan that methods for preparing precursors and functionality related to the compounds claimed herein are generally described in the literature. In these reactions, it is also possible to make use of variants which are themselves known to those of ordinary skill in this art, but are not mentioned in greater detail. The skilled artisan given the literature and this disclosure is well equipped to prepare any of the compounds. [0118] It is recognized that the skilled artisan in the art of organic chemistry can readily carry out manipulations without further direction, that is, it is well within the scope and practice of the skilled artisan to carry out these manipulations. These include reduction of carbonyl compounds to their corresponding alcohols, oxidations, acylations, aromatic substitutions, both electrophilic and nucleophilic, etherifications, esterification and saponification and the like. These manipulations are discussed in standard texts such as March Advanced Organic Chemistry (Wiley), Carey and Sundberg, Advanced Organic Chemistry (incorporated herein by reference in their entirety) and the like. All the intermediate compounds of the present disclosure were used without further purification unless otherwise specified. [0119] The skilled artisan will readily appreciate that certain reactions are best carried out when other functionality is masked or protected in the molecule, thus avoiding any undesirable side reactions and/or increasing the yield of the reaction. Often the skilled artisan utilizes protecting groups to accomplish such increased yields or to avoid the undesired reactions. These reactions are found in the literature and are also well within the scope of the skilled artisan. Examples of many of these manipulations can be found for example in T. Greene and P. Wuts Protecting Groups in Organic Synthesis, 4th Ed., John Wiley & Sons (2007), incorporated herein by reference in its entirety. [0120] The following example schemes are provided for the guidance of the reader, and represent preferred methods for making the compounds exemplified herein. These methods are not limiting, and it will be apparent that other routes may be employed to prepare these compounds. Such methods specifically include solid phase based chemistries, including combinatorial chemistry. The skilled artisan is thoroughly equipped to prepare these compounds by those methods given the literature and this disclosure. The compound numberings used in the synthetic schemes depicted below are meant for those specific schemes only, and should not be construed as or confused with same numberings in other sections of the application. [0121] Trademarks used herein are examples only and reflect illustrative materials used at the time of the present disclosue. The skilled artisan will recognize that variations in lot, manufacturing processes, and the like, are expected. Hence the examples, and the trademarks used in them are non-limiting, and they are not intended to be limiting, but are merely an illustration of how a skilled artisan may choose to perform one or more of the embodiments of the disclosure. [0122] The following abbreviations have the indicated meanings: Aib = aminoisobutyric acid Bn = benzyl Boc = tert-butoxycarbonyl Bu = butyl Dde = 2-Acetyldimedone DIPEA = diisopropylethylamine DMF = dimethylformamide EDC = 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Et = ethyl Fmoc = fluorenylmethoxycarbonyl HATU = hexafluorophosphate azabenzotriazole tetramethyl uranium HBTU = hexafluorophosphate benzotriazole tetramethyl uranium HMDS = hexamethyldisilazane HPLC = high-performance liquid chromatography Me = methyl NaHMDS = sodium hexamethyldisilazide NMR = nuclear magnetic resonance PCC = pyridinium chlorochromate PEG = polyethylene glycol Ph = phenyl RT= room temperature tBu = tert-butyl TFA = trifluoroacetic acid THF = tetrahydrofuran TMS = trimethylsilyl [0123] The following example schemes are provided for the guidance of the reader, and collectively represent an example method for making the compounds provided herein. Furthermore, other methods for preparing compounds described herein will be readily apparent to the person of ordinary skill in the art in light of the following reaction schemes and examples. Unless otherwise indicated, all variables are as defined above. EXAMPLE 1 Synthesis of 4-[2-[2-[4-[[4-[4-[[6-(6-aminopyrazin-2-yl)imidazo[1,2-a]pyr azin-8- yl]amino]phenyl]piperazin-1-yl]methyl]triazol-1-yl]ethoxy]et hylamino]-2-(2,6-dioxo-3- piperidyl)isoindoline-1,3-dione (130) [0124] 4-[2-[2-[4-[[4-[4-[[6-(6-aminopyrazin-2-yl)imidazo[1,2-a]pyr azin-8- yl]amino]phenyl]piperazin-1-yl]methyl]triazol-1-yl]ethoxy]et hylamino]-2-(2,6-dioxo-3- piperidyl)isoindoline-1,3-dione (130) may be prepared via the reaction of alkyne-1 and azide-1 according to Procedure A shown in Scheme A below. S h A [0125] To a solution of 6-(6-aminopyrazin-2-yl)-N-[4-(4-prop-2-ynylpiperazin-1- yl)phenyl]imidazo[1,2-a]pyrazin-8-amine (40 mg, 0.090 mmol) and 4-[2-(2- azidoethoxy)ethylamino]-2-(2,6-dioxo-3-piperidyl)isoindoline -1,3-dione (36.32 mg, 0.090 mmol) in THF (2 mL) and water (0.2 mL), sodium ascorbate (9.31 mg, 0.050 mmol) and CuSO4 (7.5 mg, 0.050 mmol) were added and the reaction mixture was stirred at RT for 24 h. After completion of the reaction, as monitored by LCMS, the reaction mixture was evaporated in vacuo, and the crude was purified by Prep-HPLC followed by lyophilization to give 4-[2-[2-[4-[[4-[4-[[6-(6- aminopyrazin-2-yl)imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]pi perazin-1-yl]methyl]triazol-1- yl]ethoxy]ethylamino]-2-(2,6-dioxo-3-piperidyl)isoindoline-1 ,3-dione (130) (20 mg, 0.0233 mmol, 25% yield) as a yellow solid. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.88 – 10.58 (m, 1H), 8.97 (s, 1H), 8.60 (s, 1H), 8.52 (s, 1H), 8.05 (s, 1H), 7.94 (s, 1H), 7.89 (d, J = 9.2 Hz, 3H), 7.60 (s, 1H), 7.59 – 7.55 (m, 1H), 7.10 (d, J = 8.6 Hz, 1H), 7.04 (d, J = 7.0 Hz, 1H), 6.94 (d, J = 8.9 Hz, 2H), 6.51 (t, J = 6.0 Hz, 1H), 6.10 (d, J = 4.7 Hz, 2H), 5.01 (dd, J = 5.5, 12.4 Hz, 1H), 4.53 (t, J = 5.4 Hz, 2H), 3.90 (t, J = 5.4 Hz, 2H), 3.65 (dd, J = 6.0, 11.4 Hz, 4H), 3.47 (q, J = 5.6 Hz, 2H), 3.12 (t, J = 5.0 Hz, 4H), 2.90 – 2.80 (m, 1H), 2.67 – 2.51 (m, 6H), 2.11 – 2.01 (m, 1H). LCMS-ESI (pos.) m/z: 812.48 (M+H) ⁺ .

EXAMPLE 2 Synthesis of Alkyne-1 [0126] Step-1: Synthesis of benzyl 4-(4-nitrophenyl)piperazine-1-carboxylate: To a stirred solution of 1-(4-nitrophenyl)piperazine [6269-89-2] (1000 mg, 4.83 mmol) in THF (20 mL) at 0 °C, Et3N (1.02 mL, 7.24 mmol) was added and stirred for 10 min. Then benzyl chloroformate (0.83 mL, 5.79 mmol) was added dropwise to the reaction mixture and stirred for 1 h at 0 °C. Then the stirring was continued for another 1 h at RT. After completion of the reaction, as monitored by TLC, the reaction mixture was diluted with DCM and the organic layer was washed with sat. NaHCO3 solution, dried over anhydrous Na ₂ SO ₄ and concentrated in vacuo. The crude was purified by Combiflash column chromatography (silica gel, 230-400 mesh), eluting with 30% ethyl acetate in hexanes to give benzyl 4-(4-nitrophenyl)piperazine-1-carboxylate (1200 mg, 3.515 mmol, 72.85% yield) as a yellow solid. LCMS-ESI (Pos.) m/z: 342.0 (M+H) ⁺ . [0127] Step-2: Synthesis of benzyl 4-(4-aminophenyl)piperazine-1-carboxylate: To a stirred solution of benzyl 4-(4-nitrophenyl)piperazine-1-carboxylate. (2300 mg, 6.74 mmol) in ethanol (50 mL), SnCl2.2H2O (9882.43 mg, 43.8 mmol) was added and the reaction mixture was heated at 70 °C for 12 h. After completion of the reaction, as monitored by TLC, the pH of the reaction mixture was made slightly basic (pH 7-8) by addition of sat. NaHCO ₃ solution. The resulting alkaline solution was transferred to a separation funnel and the aqueous layer was extracted thrice with ethyl acetate. The combined organic layers was dried over anhydrous Na ₂ SO ₄ , and concentrated in vacuo to give the crude. The crude was purified by Combiflash column chromatography (silica gel, 230-400 mesh), eluting with 5% MeOH in DCM to give benzyl 4-(4- aminophenyl)piperazine-1-carboxylate (1700 mg, 5.459 mmol, 81.03% yield) as a brown sticky gum. LCMS-ESI (pos.) m/z: 312.1 (M+H) ⁺ . [0128] Step-3: Synthesis of benzyl 4-[4-[(6-bromoimidazo[1,2-a]pyrazin-8- yl)amino]phenyl]piperazine-1-carboxylate: To a stirred solution of benzyl 4-(4- aminophenyl)piperazine-1-carboxylate (1300 mg, 4.17 mmol), 6,8-dibromoimidazo[1,2- a]pyrazine (1271.74 mg, 4.59 mmol) in DMF (10 mL), DIPEA (1.87 mL, 10.44 mmol) was added and the reaction mixture was heated at 85 °C for 16 h. After completion of the reaction, as monitored by LCMS, the reaction mixture was poured into ice-cold water and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous Na ₂ SO _4, and concentrated in vacuo to give the crude. The crude was purified by Combiflash column chromatography (silica gel, 230-400 mesh), eluting with 80% ethyl acetate in hexanes to give benzyl 4-[4-[(6- bromoimidazo[1,2-a]pyrazin-8-yl)amino]phenyl]piperazine-1-ca rboxylate (1700 mg, 3.351 mmol, 80.25% yield) as a light yellow solid. LCMS-ESI (pos.) m/z: 507.1 (M+H) ⁺ . [0129] Step-4: Synthesis of benzyl 4-[4-[(6-bromoimidazo[1,2-a]pyrazin-8-yl)-tert- butoxycarbonyl-amino]phenyl]piperazine-1-carboxylate: To a stirred solution of benzyl 4-[4-[(6- bromoimidazo[1,2-a]pyrazin-8-yl)amino]phenyl]piperazine-1-ca rboxylate (500 mg, 0.990 mmol) in DCM (15 mL), DMAP (12.04 mg, 0.100 mmol)and boc-anhydride (0.45 mL, 1.97 mmol) was added and the reaction mixture was heated at 65 °C for 3 h. After completion of reaction as monitored by TLC, the solvent was evaporated in vacuo and the crude was purified by Combiflash column chromatography (silica gel, 230-400 mesh), eluting with 80% ethyl acetate in hexanes to give benzyl 4-[4-[(6-bromoimidazo[1,2-a]pyrazin-8-yl)-tert-butoxycarbony l- amino]phenyl]piperazine-1-carboxylate solid (510 mg, 0.839 mmol, 85.19% yield) as a yellow solid. LCMS-ESI (pos.) m/z: 607.5 (M+H) ⁺ . [0130] Step 5A: Synthesis of tert-butyl N-tert-butoxycarbonyl-N-[6-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazin-2-yl]carbamate: To a mixture of 6-bromopyrazin-2- amine (1 g, 5.75 mmol) in DCM (3 mL) was added Boc-anhydride (5.28 mL, 22.99 mmol) at RT followed by DMAP (0.7 g, 5.75 mmol). The reaction was heated to 65 °C for 1 h, cooled to RT, and the reaction was partitioned between water and DCM, and the organic layer was purified by Combiflash (230-400 mesh silica gel), eluting with 3% EtOAc in hexane to give tert-butyl N-(6- bromopyrazin-2-yl)-N-tert-butoxycarbonyl-carbamate (1300 mg, 3.474 mmol, 60.44% yield) as an white solid. LCMS-ESI (pos.) m/z: 373.9 (M+H) ⁺ , 395.9 (M+Na) ⁺ . [0131] In a sealed tube, to a degassed stirred solution of tert-butyl N-(6-bromopyrazin- 2-yl)-N-tert-butoxycarbonyl-carbamate (225 mg, 0.600 mmol), 4,4,4’,4’,5,5,5’,5’-octamethyl- 2,2’-bi(1,3,2-dioxaborolane) (167.95 mg, 0.660 mmol) and KOAc (147.51 mg, 1.5 mmol) in 1,4- dioxane (3 mL), palladium(II) acetate (6.75 mg, 0.030 mmol) and tricyclohexylphosphine (16.86 mg, 0.060 mmol) was added and the mixture was further degassed for few minutes using N2 balloon. Then the reaction mixture was heated at 90 °C for 1 h. The reaction was removed from heat and allowed to cool to RT. The reaction contents were filtered through a celite bed, and the filter cake was washed with EtOAc. The resulting filtrate was concentrated to give the crude. The crude was re-dissolved in ethyl acetate and washed with water and brine, dried over anhydrous Na ₂ SO ₄ and concentrated in vacuo to give crude tert-butyl N-tert-butoxycarbonyl-N-[6-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazin-2-yl]carbamate (180 mg, 0.427 mmol, 71.06% yield), as a sticky gum. The crude product was used for step 5B without further purification. [0132] Step-5B: Synthesis of benzyl 4-[4-[[6-[6-[bis(tert- butoxycarbonyl)amino]pyrazin-2-yl]imidazo[1,2-a]pyrazin-8-yl ]-tert-butoxycarbonyl- amino]phenyl]piperazine-1-carboxylate: In a sealed tube, to a degassed stirred solution of benzyl 4-[4-[(6-bromoimidazo[1,2-a]pyrazin-8-yl)-tert-butoxycarbony l-amino]phenyl]piperazine-1- carboxylate (500 mg, 0.820 mmol) and crude tert-butyl N-tert-butoxycarbonyl-N-[6-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazin-2-yl]carbamate (1213.62 mg, 2.88 mmol) and Na2CO3 (0.26 mL, 2.47 mmol) in dimethoxyethane (10 mL) and water (0.5 mL), and Pd(PPh3)4 (95.11 mg, 0.080 mmol) was added and the mixture was further degassed for few min. using N ₂ . Then the reaction mixture was heated at 90 °C for 12 h. The reaction was removed from heat and allowed to cool to RT. The reaction mixture was filtered through celite and washed with EtOAc. The filtrate was concentrated and re-dissolved in ethyl acetate. The organic layer was washed with water and brine, and dried over anhydrous Na ₂ SO ₄ and concentrated in vacuo to give the crude. The crude was purified by Combiflash column chromatography (silica gel, 230-400 mesh), eluting with 75% ethyl acetate in hexane to give benzyl 4-[4-[[6-[6-[bis(tert- butoxycarbonyl)amino]pyrazin-2-yl]imidazo[1,2-a]pyrazin-8-yl ]-tert-butoxycarbonyl- amino]phenyl]piperazine-1-carboxylate (400 mg, 0.487 mmol, 59.13% yield) as a light yellow sticky solid. LCMS-ESI (pos.) m/z: 822.0 (M+H) ⁺ . [0133] Step-6: Synthesis of tert-butyl N-[6-[6-[bis(tert- butoxycarbonyl)amino]pyrazin-2-yl]imidazo[1,2-a]pyrazin-8-yl ]-N-(4-piperazin-1- ylphenyl)carbamate: To a stirred solution of benzyl 4-[4-[[6-[6-[bis(tert- butoxycarbonyl)amino]pyrazin-2-yl]imidazo[1,2-a]pyrazin-8-yl ]-tert-butoxycarbonyl- amino]phenyl]piperazine-1-carboxylate (1500 mg, 1.82 mmol)) in IPA (50 mL) was added Pd-C (2000 mg, 18.87 mmol). Then the reaction mixture was stirred under hydrogen atmosphere (balloon pressure) for 72 h at RT. After completion of the reaction as monitored by LCMS, the reaction mixture was filtered through a celite bed and washed with ethyl acetate. The filtrate was concentrated in vacuo to give the crude tert-butyl N-[6-[6-[bis(tert- butoxycarbonyl)amino]pyrazin-2-yl]imidazo[1,2-a]pyrazin-8-yl ]-N-(4-piperazin-1- ylphenyl)carbamate (1000 mg, 1.454 mmol, 79.67% yield). LCMS-ESI (pos.) m/z: 688.2 (M+H) ⁺ . [0134] Step-7: Synthesis of tert-butyl N-[6-[6-[bis(tert- butoxycarbonyl)amino]pyrazin-2-yl]imidazo[1,2-a]pyrazin-8-yl ]-N-[4-(4-prop-2-ynylpiperazin- 1-yl)phenyl]carbamate: To a stirred solution of crude tert-butyl N-[6-[6-[bis(tert- butoxycarbonyl)amino]pyrazin-2-yl]imidazo[1,2-a]pyrazin-8-yl ]-N-(4-piperazin-1- ylphenyl)carbamate (1000 mg, 1.45 mmol) in DCM (40 mL), DIPEA (0.39 mL, 2.18 mmol), 3- bromoprop-1-yne (0.18 mL, 1.6 mmol) was added and the reaction mixture was heated at 45 °C for 12 h. The resultant solution was concentrated and the crude purified by Combiflash column chromatography using 70% ethyl acetate in hexane to give tert-butyl N-[6-[6-[bis(tert- butoxycarbonyl)amino]pyrazin-2-yl]imidazo[1,2-a]pyrazin-8-yl ]-N-[4-(4-prop-2-ynylpiperazin- 1-yl)phenyl]carbamate (375 mg, 0.516 mmol, 35.53% yield) and tert-butyl N-[6-[6-(tert- butoxycarbonylamino)pyrazin-2-yl]imidazo[1,2-a]pyrazin-8-yl] -N-[4-(4-prop-2-ynylpiperazin-1- yl)phenyl]carbamate (100 mg, 0.159 mmol, 10.99% yield). LCMS-ESI (pos.) m/z: 725.9 (M+H) ⁺ and 626.3 (M+H) ⁺ for two products respectively. [0135] Step-8: Synthesis of 6-(6-aminopyrazin-2-yl)-N-[4-(4-prop-2-ynylpiperazin-1- yl)phenyl]imidazo[1,2-a]pyrazin-8-amine: To a stirred solution of tert-butyl N-[6-[6-[bis(tert- butoxycarbonyl)amino]pyrazin-2-yl]imidazo[1,2-a]pyrazin-8-yl ]-N-[4-(4-prop-2-ynylpiperazin- 1-yl)phenyl]carbamate (70 mg, 0.100 mmol) in DCM (2 mL) at 0 °C, TFA (0.25 mL, 3.27 mmol) was added and the reaction mixture was stirred for 30 min at 0 °C. Then the reaction mixture was stirred at RT for overnight. After completion of the reaction as monitored by LCMS, the solvent and excess TFA was evaporated in vacuo. The crude was re-dissolved in DCM and neutralized to basic pH using aqueous solution of NaHCO3. Then the organic layer was separated, dried over anhydrous Na ₂ SO ₄ and concentrated in vacuo. The residue was triturated with n-pentane to give crude 6-(6-aminopyrazin-2-yl)-N-[4-(4-prop-2-ynylpiperazin-1-yl)ph enyl]imidazo[1,2- a]pyrazin-8-amine (35 mg, 0.082 mmol, 85.3% yield) as an off-white sticky solid. LCMS-ESI (pos.) m/z: 426.2 (M+H) ⁺ . EXAMPLE 3 Synthesis of Alkyne-1 [0136] Step 1: Synthesis of 4-[2-[2-[4-[[4-[4-[[6-(6-aminopyrazin-2-yl)imidazo[1,2- a]pyrazin-8-yl]amino]phenyl]piperazin-1-yl]methyl]triazol-1- yl]ethoxy]ethylamino]-2-(2,6- dioxo-3-piperidyl)isoindoline-1,3-dione: To a solution of 6-(6-aminopyrazin-2-yl)-N-[4-(4-prop- 2-ynylpiperazin-1-yl)phenyl]imidazo[1,2-a]pyrazin-8-amine (40 mg, 0.090 mmol) and 4-[2-(2- azidoethoxy)ethylamino]-2-(2,6-dioxo-3-piperidyl)isoindoline -1,3-dione (36.32 mg, 0.090 mmol) in THF (2 mL) and water (0.2 mL), sodium ascorbate (9.31 mg, 0.050 mmol) and CuSO ₄ (7.5 mg, 0.050 mmol) were added and the reaction mixture was stirred at RT for 24 h. After completion of the reaction, as monitored by LCMS, the reaction mixture was evaporated in vacuo, and the crude was purified by Prep-HPLC followed by lyophilization to give 4-[2-[2-[4-[[4-[4-[[6-(6- aminopyrazin-2-yl)imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]pi perazin-1-yl]methyl]triazol-1- yl]ethoxy]ethylamino]-2-(2,6-dioxo-3-piperidyl)isoindoline-1 ,3-dione (130) (20 mg, 0.0233 mmol, 25% yield) as a yellow solid. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.88 – 10.58 (m, 1H), 8.97 (s, 1H), 8.60 (s, 1H), 8.52 (s, 1H), 8.05 (s, 1H), 7.94 (s, 1H), 7.89 (d, J = 9.2 Hz, 3H), 7.60 (s, 1H), 7.59 – 7.55 (m, 1H), 7.10 (d, J = 8.6 Hz, 1H), 7.04 (d, J = 7.0 Hz, 1H), 6.94 (d, J = 8.9 Hz, 2H), 6.51 (t, J = 6.0 Hz, 1H), 6.10 (d, J = 4.7 Hz, 2H), 5.01 (dd, J = 5.5, 12.4 Hz, 1H), 4.53 (t, J = 5.4 Hz, 2H), 3.90 (t, J = 5.4 Hz, 2H), 3.65 (dd, J = 6.0, 11.4 Hz, 4H), 3.47 (q, J = 5.6 Hz, 2H), 3.12 (t, J = 5.0 Hz, 4H), 2.90 – 2.80 (m, 1H), 2.67 – 2.51 (m, 6H), 2.11 – 2.01 (m, 1H). LCMS-ESI (pos.) m/z: 812.48 (M+H) ⁺ EXAMPLE 4 Synthesis of azide-2 [0137] Synthesis of 4-[2-[2-(2-azidoethoxy)ethoxy]ethylamino]-2-(2,6-dioxo-3- piperidyl)isoindoline-1,3-dione (azide-2): A stirred solution of 2-(2,6-dioxo-3-piperidyl)-4- fluoro-isoindoline-1,3-dione (100 mg, 0.360 mmol) and 2-[2-(2- azidoethoxy)ethoxy]ethanamine and DIPEA (0.19 mL, 1.09 mmol) in DMA (2 mL) was stirred at room over 16 h. The reaction was concentrated to dryness and the residue was taken up in EtOAc (100 mL) and the organics washed with water (2 x100 mL) then sat. brine solution (1 x 100 mL). The organic layer was dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 50% EtOAc in hexanes to give 4-[2-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]ethylamino]-2-(2,6-d ioxo-3- piperidyl)isoindoline-1,3-dione (azide-2) (100 mg, 0.2108 mmol, 58.22% yield). LCMS-ESI (pos.) m/z: 431.0 (M+H) ⁺ . EXAMPLE 5 Synthesis of azide-3 [0138] Synthesis of 4-(3-azidopropylamino)-2-(2,6-dioxo-3-piperidyl)isoindoline- 1,3- dione (azide-3): To a stirred solution of 2-(2,6-dioxo-3-piperidyl)-4-fluoro-isoindoline-1,3-dione (500 mg, 1.81 mmol), 3-azidopropan-1-amine (199.36 mg, 1.99 mmol) in DMA (5 mL) was added DIPEA (0.94 mL, 5.43 mmol) at 0 °C and stirred at 90 °C for 16 h. The reaction mixture was diluted with EtOAc and washed with water (1 x 30 mL) and sat. brine solution (5 x 30 mL). The organic layer was dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 40-50% EtOAc in hexanes followed by purification by Prep-HPLC to give 4-(3-azidopropylamino)-2-(2,6-dioxo-3- piperidyl)isoindoline-1,3-dione (azide-3) (90 mg, 0.252 mmol, 13.93% yield) as a an yellow solid. LCMS-ESI (pos.) m/z: 357.0 (M+H) ⁺ . EXAMPLE 6 Synthesis of azide-4 [0139] Synthesis of 2-(2,6-dioxo-3-piperidyl)-5-[3-[2-(2-hydroxyethoxy)ethoxy]pr op- 1-ynyl]isoindoline-1,3-dione (azide-4-A): To a stirred solution of 5-bromo-2-(2,6-dioxo-3- piperidyl)isoindoline-1,3-dione (500 mg, 1.48 mmol) in THF (15 mL) were added 2-(2- ethynoxyethoxy)ethanol (386.02 mg, 2.97 mmol) and bis(triphenylphosphine)palladium(II) dichloride (156.15 mg, 0.220 mmol) respectively at 90 °C for 3 h. Progress of the reaction was monitored by TLC and LCMS. After completion of the reaction, the reaction mixture was passed through celite and the filtrate was combined with the reaction another reaction crude (200 mg) and purified by Combiflash column chromatography (230-400 mesh silica gel) eluting with 5% MeOH in DCM to give 2-(2,6-dioxo-3-piperidyl)-5-[3-[2-(2-hydroxyethoxy)ethoxy]pr op-1- ynyl]isoindoline-1,3-dione (azide-4-A) (294 mg, 0.734 mmol, 49.51% yield). LCMS-ESI (pos.) m/z: 401.2 (M+H) ⁺ . [0140] Step-2: Synthesis of 2-(2,6-dioxo-3-piperidyl)-5-[3-[2-(2- hydroxyethoxy)ethoxy]propyl]isoindoline-1,3-dione (azide-4-B): A stirred solution of 2-(2,6- dioxo-3-piperidyl)-5-[3-[2-(2-hydroxyethoxy)ethoxy]prop-1-yn yl]isoindoline-1,3-dione (azide- 4-A) (45 mg, 0.110 mmol) and 10% palladium-carbon (47.84mg, 100% w/w) in ethanol (2 mL) was stirred under hydrogen balloon pressure at RT for 2 h. After completion of the reaction, reaction mass was filtered through celite, washed with DCM and concentrated. The reaction crude was again washed with pentane and then purified by Combiflash column chromatography (230- 400 mesh silica gel), eluting with 5% MeOH in DCM to give 2-(2,6-dioxo-3-piperidyl)-5-[3-[2- (2-hydroxyethoxy)ethoxy]propyl]isoindoline-1,3-dione (azide-4-B) (39 mg, 0.096 mmol, 85.80% yield). LCMS-ESI (pos.) m/z: 405.4 (M+H) ⁺ . [0141] Step-3: Synthesis of 2-[2-[3-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-4- yl]propoxy]ethoxy]ethyl 4-methylbenzenesulfonate (azide-4-B’): To a stirred solution of 2-(2,6- dioxo-3-piperidyl)-4-[3-[2-(2-hydroxyethoxy)ethoxy]propyl]is oindoline-1,3-dione (azide-4-B) (30 mg, 0.070 mmol) in dry DCM (10 mL), triethylamine (31.04 uL, 0.220 mmol) and 4-toluenesulfonyl chloride (28.29 mg, 0.150 mmol) were added and stirred at RT for 16 h. After completion of the reaction, the solvent was evaporated in vacuo. The crude mixture was extracted with EtOAc (2 x 50 mL) and washed with water (2 x 50 mL). The organic layer was dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by prep TLC eluting with 60% EtOAc in hexanes to give 2-[2-[3-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-4- yl]propoxy]ethoxy]ethyl 4-methylbenzenesulfonate (azide-4-B’) (25 mg, 0.045 mmol, 60.33% yield) as a colorless liquid. LCMS-ESI (pos.) m/z: 559.1 (M+H) ⁺ . [0142] Step-4: Synthesis of 5-[3-[2-(2-azidoethoxy)ethoxy]propyl]-2-(2,6-dioxo-3- piperidyl)isoindoline-1,3-dione (azide-4): To a stirred solution of 2-[2-[3-[2-(2,6-dioxo-3- piperidyl)-1,3-dioxo-isoindolin-5-yl]propoxy]ethoxy]ethyl 4-methylbenzenesulfonate (azide-4- B’) (160 mg, 0.290 mmol) in DMF (3 mL), sodium azide (144.65 mg, 1.43 mmol) was added and the reaction mixture was heated at 90 °C or 2 h. The reaction mixture was taken in EtOAc (20 mL) and the organics was washed with water (2 x 20 mL) and sat. brine solution (1 x 20 mL). The organic layer was dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 60% EtOAc in hexane to give 5-[3-[2-(2-azidoethoxy)ethoxy]propyl]-2-(2,6-dioxo-3-piperid yl)isoindoline-1,3- dione (azide-4) (75 mg, 0.175 mmol, 60.98% yield). LCMS-ESI (neg.) m/z: 428.2 (M-H)-. EXAMPLE 7 Synthesis of azide-5 [0143] Step-1: Synthesis of 2-(2,6-dioxo-3-piperidyl)-5-[3-[2-[2-(2- hydroxyethoxy)ethoxy]ethoxy]prop-1-ynyl]isoindoline-1,3-dion e (azide-5-A): To a stirred solution of 2-[2-(2-prop-2-ynoxyethoxy)ethoxy]ethanol (111.66 mg, 0.590 mmol), 5-bromo-2- (2,6-dioxo-3-piperidyl)isoindoline-1,3-dione (100 mg, 0.300 mmol) and DIPEA (0.21 mL, 1.19 mmol) in THF (5 mL) was de-gassed with N2 for 5 min, then added copper(I) iodide (8.47 mg, 0.040 mmol) and PdCl ₂ (PPh ₃ ) ₂ (31.19 mg, 0.040 mmol). The reaction was stirred at 90°C for 16 h. The reaction mass filtered through celite, and the filtrate was evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 5%MeOH in DCM to give 2-(2,6-dioxo-3-piperidyl)-5-[3-[2-[2-(2- hydroxyethoxy)ethoxy]ethoxy]prop-1-ynyl]isoindoline-1,3-dion e (azide-5-A) (70 mg, 0.157 mmol, 53.1% yield). LCMS-ESI (pos.) m/z: 445.4 (M+H) ⁺ . [0144] Step-2: Synthesis of 2-(2,6-dioxo-3-piperidyl)-5-[3-[2-[2-(2- hydroxyethoxy)ethoxy]ethoxy]propyl]isoindoline-1,3-dione (azide-5-B): A stirred solution of 2- (2,6-dioxo-3-piperidyl)-5-[3-[2-[2-(2-hydroxyethoxy)ethoxy]e thoxy]prop-1-ynyl]isoindoline- 1,3-dione (azide-5-A) (76 mg, 0.170 mmol) and 10% Pd/C (70 mg, 100% w/w) in ethanol (2 mL) under hydrogen balloon pressure was stirred at RT for 2 h. The reaction mass filtered through celite, and the filtrate was evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 5% MeOH in DCM to give 2-(2,6-dioxo- 3-piperidyl)-5-[3-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]propy l]isoindoline-1,3-dione (azide-5- B) (35 mg, 0.078 mmol, 45.64% yield). LCMS-ESI (pos.) m/z: 449.5 (M+H) ⁺ . [0145] Step-3: Synthesis of 2-[2-[2-[3-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo- isoindolin-5-yl]propoxy]ethoxy]ethoxy]ethyl 4-methylbenzenesulfonate (azide-5-B’): A stirred solution of 2-(2,6-dioxo-3-piperidyl)-5-[3-[2-[2-(2- hydroxyethoxy)ethoxy]ethoxy]propyl]isoindoline-1,3-dione (azide-5-B) (210 mg, 0.470 mmol), 4-toluenesulfonyl chloride (267.82 mg, 1.4 mmol) and triethylamine (0.26 mL, 1.87 mmol) in DCM (5 mL) at 0 °C, the reaction was allowed to warm to room temperature and stirred at RT for 16 h. The reaction was evaporated in vacuo and the crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 5% MeOH in DCM to give 2-[2- [2-[3-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-5-yl]p ropoxy]ethoxy]ethoxy]ethyl 4- methylbenzenesulfonate (azide-5B’) (240 mg, 0.398 mmol, 85.05% yield). LCMS-ESI (pos.) m/z: 620.0 (M+NH4) ⁺ . [0146] Step-4: Synthesis of 5-[3-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]propyl]-2-(2,6- dioxo-3-piperidyl)isoindoline-1,3-dione (azide-5): A stirred solution of 2-[2-[2-[3-[2-(2,6-dioxo- 3-piperidyl)-1,3-dioxo-isoindolin-5-yl]propoxy]ethoxy]ethoxy ]ethyl 4-methylbenzenesulfonate (azide-5B’) (240 mg, 0.400 mmol) and sodium azide (129.43 mg, 1.99 mmol) in DMF (2 mL) was stirred at 90 °C for 3 h. The reaction mixture was filtered over celite, and the filtrate was evaporated in vacuo. The crude was taken in DCM (50 mL) and washed with water (2 x 20 mL) and sat. brine solution (1 x 20 mL). The organics layer was dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel) eluting with 80% EtOAc in hexanes to give 5-[3-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]propyl]-2- (2,6-dioxo-3-piperidyl)isoindoline-1,3-dione (azide-5) (90 mg, 0.190 mmol, 47.73% yield). LCMS-ESI (pos.) m/z: 491.1 (M+NH ₄ ) ⁺ . EXAMPLE 8 Synthetic scheme for azide-6: [0147] Step-1: Synthesis of 2-(2,6-dioxo-3-piperidyl)-5-[3-(2-hydroxyethoxy)prop-1- ynyl]isoindoline-1,3-dione (azide-6-A): To a stirred solution of 5-bromo-2-(2,6-dioxo-3- piperidyl)isoindoline-1,3-dione (500 mg, 1.48 mmol) in THF (15 mL) were added 2- ethynoxyethanol (255.36 mg, 2.97 mmol) and bis(triphenylphosphine)palladium(II) dichloride (156.15 mg, 0.220 mmol) and stirred at 90°C for 16 h. After the completion of the reaction, the reaction mixture was passed through celite and the filtrate was combined with another reaction crude (200 mg) and the combined crude was purified by Combiflash column chromatography (230-400 mesh silica gel) eluting with 2-(2,6-dioxo-3-piperidyl)-5-[3-(2-hydroxyethoxy)prop-1- ynyl]isoindoline-1,3-dione (azide-6-A) (305 mg, 0.856 mmol, 57.71% yield). LCMS-ESI (neg.) m/z: 355.3 (M-H)-. [0148] Step-2: Synthesis of 2-(2,6-dioxo-3-piperidyl)-5-[3-(2- hydroxyethoxy)propyl]isoindoline-1,3-dione (azide-6-B): A stirred solution of 2-(2,6-dioxo-3- piperidyl)-5-[3-(2-hydroxyethoxy)prop-1-ynyl]isoindoline-1,3 -dione (azide-6-A) (305 mg, 0.860 mmol) and 10% Pd/C (318.82 mg, 100% w/w) in ethanol (5 mL) was stirred under hydrogen balloon pressure at RT for 2 h. After completion of the reaction, the reaction mass was filtered over celite and washed with DCM. The filtrate was evaporated in vacuo and the reaction mass washed with pentane and then purified by Combiflash column chromatography (230-400 mesh silica gel) eluting with 5% MeOH in DCM to give 2-(2,6-dioxo-3-piperidyl)-5-[3-(2- hydroxyethoxy)propyl]isoindoline-1,3-dione (azide-6-B) (220 mg, 0.611 mmol, 71.32% yield). LCMS-ESI (pos.) m/z: 361.1 (M+H) ⁺ . [0149] Step-3: Synthesis of 2-[3-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-4- yl]propoxy]ethyl 4-methylbenzenesulfonate (azide-6-B’): To a stirred solution of 2-(2,6-dioxo-3- piperidyl)-4-[3-(2-hydroxyethoxy)propyl]isoindoline-1,3-dion e (azide-6-B) (220 mg, 0.610 mmol) in dry DCM (10 mL), triethylamine (255.45 uL, 1.83 mmol) and 4-toluenesulfonyl chloride (349.18 mg, 1.83 mmol) was added and stirred at RT for 16 h. After completion of reaction, solvent was removed in vacuo and the crude mixture was extracted with EtOAc (2 x 50 mL) and washed with water (2 x 50 mL). The organic layer was dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude product was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 40% EtOAc in hexanes to give 2-[3-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo- isoindolin-4-yl]propoxy]ethyl 4-methylbenzenesulfonate (azide-6-B’) (190 mg, 0.369 mmol, 60.48% yield) as a colorless liquid. LCMS-ESI (pos.) m/z: 515.2(M+H) ⁺ . [0150] Step-4: Synthesis of 5-[3-(2-azidoethoxy)propyl]-2-(2,6-dioxo-3- piperidyl)isoindoline-1,3-dione (azide-6): 2-[3-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin- 5-yl]propoxy]ethyl 4-methylbenzenesulfonate (azide-6-B’) (190 mg, 0.370 mmol) was taken in DMF (3 mL) and sodium azide (186.47 mg, 1.85 mmol) was added to it. The reaction mixture was heated at 90 °C or 2 h. The reaction mixture was taken up in EtOAc (20 mL) and washed with water (2 x 20 mL) and sat. brine solution (1 x 20 mL). The organic layer was dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 60% EtOAc in hexane and then again purified by prep HPLC to give 5-[3-(2-azidoethoxy)propyl]-2-(2,6-dioxo-3-piperidyl)isoindo line-1,3-dione (azide-6) (55 mg, 0.143 mmol, 38.65% yield). LCMS-ESI (neg.) m/z: 384.2 (M-H)-. EXAMPLE 9 Synthetic scheme for azide-7: [0151] Synthesis of 4-[2-[2-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]ethoxy]ethylamino ]- 2-(2,6-dioxo-3-piperidyl)isoindoline-1,3-dione (azide-7): To a stirred solution of 2-(2,6-dioxo-3- piperidyl)-4-fluoro-isoindoline-1,3-dione (100 mg, 0.360 mmol), 2-[2-[2-[2-(2- azidoethoxy)ethoxy]ethoxy]ethoxy]ethanamine (azide-7-A) (189.93 mg, 0.720 mmol) and DIPEA (0.19 mL, 1.09 mmol) in DMA (2 mL) was stirred at 80 °C for 16 h. The reaction mixture was evaporated in vacuo and the residue was taken up in EtOAc (250 mL) and washed with water (2 x 250 mL) and sat. brine solution (1 x 250 mL). The organic layer was dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 70% EtOAc in hexanes to give 4-[2-[2- [2-[2-(2-azidoethoxy)ethoxy]ethoxy]ethoxy]ethylamino]-2-(2,6 -dioxo-3-piperidyl)isoindoline- 1,3-dione (azide-7) (80 mg, 0.154 mmol, 28.41% yield). LCMS-ESI (pos.) m/z: 518.9 (M+H) ⁺ . EXAMPLE 10 Synthetic scheme for azide-8: [0152] Synthesis of 4-[2-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]ethylamino]-2-(2,6- dioxo-3-piperidyl)isoindoline-1,3-dione (azide-8): A stirred solution of 2-(2,6-dioxo-3-piperidyl)- 4-fluoro-isoindoline-1,3-dione (150 mg, 0.540 mmol), 2-[2-[2-(2- azidoethoxy)ethoxy]ethoxy]ethanamine (azide-8-A) (237.04 mg, 1.09 mmol) and DIPEA (0.29 mL, 1.63 mmol) in DMA (2 mL) was stirred at 90 °C for 16 h, The reaction was concentrated in vacuo and the crude was taken in EtOAc (100 mL) and washed with water (2 x 100 mL) and sat. brine solution (1 x 100 mL). The organic layer was dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 50% EtOAc in hexanes to give 4-[2-[2-[2-(2- azidoethoxy)ethoxy]ethoxy]ethylamino]-2-(2,6-dioxo-3-piperid yl)isoindoline-1,3-dione (azide- 8) (100 mg, 0.211 mmol, 38.81% yield). LCMS-ESI (pos.) m/z: 475.10 (M+H) ⁺ .

EXAMPLE 11 Synthetic scheme for azide-9: [0153] Step 1: Synthesis of 2-(2,6-dioxo-3-piperidyl)-5-(5-hydroxypent-1- ynyl)isoindoline-1,3-dione (azide-9-A): To a stirred solution of 5-bromo-2-(2,6-dioxo-3- piperidyl)isoindoline-1,3-dione (500 mg, 1.48 mmol), pent-4-yn-1-ol (374.28 mg, 4.45 mmol) in THF (3 mL) was added DIPEA (1.06 mL, 5.93 mmol) and degassed for 15 min with argon. Thereafter copper iodide (84.54 mg, 0.440 mmol) and bis(triphenylphosphine)palladium(II) dichloride (156.15 mg, 0.220 mmol) were added to the reaction mixture was purged again for 3-5 min with argon. The reaction mixture was stirred for 16 h at 70 °C. The reaction mixture was filtered through a celite pad and washed with ethyl acetate. The filtrate was evaporated in vacuo and the crude residue was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 4% MeOH in DCM to give 2-(2,6-dioxo-3-piperidyl)-5-(5-hydroxypent-1- ynyl)isoindoline-1,3-dione (azide-9-A) (300 mg, 0.882 mmol, 59.44% yield) as a brown solid. LCMS-ESI (pos.) m/z: 341.2 (M+H) ⁺ . [0154] Step-2: Synthesis of 2-(2,6-dioxo-3-piperidyl)-5-(5- hydroxypentyl)isoindoline-1,3-dione (azide-9-B): To the stirred solution of 2-(2,6-dioxo-3- piperidyl)-5-(5-hydroxypent-1-ynyl)isoindoline-1,3-dione (azide-9-A) (250 mg, 0.730 mmol) in ethanol (3 mL) was added 10% Pd-C (250 mg, 2.36 mmol) and the reaction was stirred at RT for 2 h under H2 atmosphere using a balloon. The reaction mixture was filtered through a celite pad and washed with 5% MeOH in DCM (20 mL) and the solvent was evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 2%- 2.5% MeOH in DCM to give 2-(2,6-dioxo-3-piperidyl)-5-(5-hydroxypentyl)isoindoline-1,3 -dione (azide-9-B) (200 mg, 0.581 mmol, 79.06% yield) as an off white solid. LCMS-ESI (pos.) m/z: 345.1 (M+H) ⁺ . [0155] Step-3: Synthesis of 5-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-5- yl]pentyl 4-methylbenzenesulfonate (azide-9-C): To the stirred solution of 2-(2,6-dioxo-3- piperidyl)-5-(5-hydroxypentyl)isoindoline-1,3-dione (azide-9-B) (200 mg, 0.580 mmol) in DCM (5 mL) under N2 atmosphere at 0 °C was added triethyl amine (321.42 µL, 2.32 mmol) and after 5 min p-toluenesulfonyl chloride (332.18 mg, 1.74 mmol) was added and the reaction was stirred for 16 h at RT. Crude LCMS showed presence of the product and the reaction mixture was diluted with water (5 mL) and extracted with DCM (25 mL). The organic layer was dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 1.2% MeOH in DCM to give 5-[2-(2,6-dioxo-3-piperidyl)- 1,3-dioxo-isoindolin-5-yl]pentyl 4-methylbenzenesulfonate (azide-9-C) (200 mg, 0.401 mmol, 69.07% yield) as an off white solid. LCMS-ESI (pos.) m/z: 499.1 (M+H) ⁺ . [0156] Step-4: Synthesis of 5-(5-azidopentyl)-2-(2,6-dioxo-3-piperidyl)isoindoline- 1,3-dione (azide-9): To a stirred solution of 5-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-5- yl]pentyl 4-methylbenzenesulfonate (azide-9-C) (235 mg, 0.470 mmol) and NaN3 (153.19 mg, 2.36 mmol) in DMF (2 mL) was stirred at 90 °C for 2 h. The reaction was concentrated to dryness and the residue was taken up in DCM (50 mL) and the organic layer was washed with water (2 x 20 mL) and sat. brine solution (1 x 20 mL). The organic layer was dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by Combiflash column chromatography (230- 400 mesh silica gel), eluting with 40% EtOAc in hexanes to give 5-(5-azidopentyl)-2-(2,6-dioxo- 3-piperidyl)isoindoline-1,3-dione (azide-9) (90 mg, 0.244 mmol, 51.69% yield) as a pale brown color solid. LCMS-ESI (pos.) m/z: 370.3 (M+H) ⁺ . EXAMPLE 12 Synthetic scheme for azide-10: [0157] Step-1: Synthesis of 2-(2,6-dioxo-3-piperidyl)-5-[3-[2-[2-[2-(2- hydroxyethoxy)ethoxy]ethoxy]ethoxy]prop-1-ynyl]isoindoline-1 ,3-dione (azide-10-A): To a stirred solution of 2-[2-[2-(2-prop-2-ynoxyethoxy)ethoxy]ethoxy]ethanol (azide-10A1) (344.48 mg, 1.48 mmol), 5-bromo-2-(2,6-dioxo-3-piperidyl)isoindoline-1,3-dione (250 mg, 0.740 mmol) and DIPEA (532.48 uL, 2.97 mmol) in THF (15 mL) was de-gassed using N2, and then copper(I) iodide (21.18 mg, 0.110 mmol) and PdCl2(PPh3)2 (77.97 mg, 0.110 mmol) were added and the reaction was stirred at 80 °C for 16 h. The reaction mass was filtered through celite, and the filtrate was concentrated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 5% MeOH in DCM to give 2-(2,6-dioxo- 3-piperidyl)-5-[3-[2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]et hoxy]prop-1-ynyl]isoindoline-1,3- dione (azide-10-A) (220 mg, 0.450 mmol, 60.73% yield). LCMS-ESI (pos.) m/z: 489.2 (M+H) ⁺ . [0158] Step-2: Synthesis of 2-(2,6-dioxo-3-piperidyl)-5-[3-[2-[2-[2-(2- hydroxyethoxy)ethoxy]ethoxy]ethoxy]propyl]isoindoline-1,3-di one (azide-10-B): To a stirred solution of 2-(2,6-dioxo-3-piperidyl)-5-[3-[2-[2-[2-(2- hydroxyethoxy)ethoxy]ethoxy]ethoxy]prop-1-ynyl]isoindoline-1 ,3-dione (azide-10-A) (400 mg, 0.820 mmol) in ethanol (5 mL) was added 10% Pd/C (400 mg, 100% w/w) and the reaction was stirred at RT for 2 h under hydrogen balloon pressure. The reaction mass was filtered through celite, and the filtrate was concentrated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 5% MeOH in DCM to give 2-(2,6-dioxo- 3-piperidyl)-5-[3-[2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]et hoxy]propyl]isoindoline-1,3-dione (azide-10-B) (250 mg, 0.508 mmol, 61.99% yield). LCMS-ESI (pos.) m/z: 493.6 (M+H) ⁺ . [0159] Step-3: Synthesis of 2-[2-[2-[2-[3-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo- isoindolin-5-yl]propoxy]ethoxy]ethoxy]ethoxy]ethyl 4-methylbenzenesulfonate (azide-10-B’): A stirred solution of 2-(2,6-dioxo-3-piperidyl)-5-[3-[2-[2-[2-(2- hydroxyethoxy)ethoxy]ethoxy]ethoxy]propyl]isoindoline-1,3-di one (azide-10-B) (210 mg, 0.430 mmol), 4-toluenesulfonyl chloride (243.87 mg, 1.28 mmol) and trimethylamine (0.24 mL, 1.71 mmol) in DCM (5 mL) at 0 °C, was stirred at RT for 16h. The reaction mass was evaporated in vacuo, and the crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 80% EtOAc in hexanes to give 2-[2-[2-[2-[3-[2-(2,6-dioxo-3-piperidyl)-1,3- dioxo-isoindolin-5-yl]propoxy]ethoxy]ethoxy]ethoxy]ethyl 4-methylbenzenesulfonate (azide-10- B`) (250 mg, 0.387 mmol, 90.66% yield).LCMS-ESI (pos.) m/z: 663.8 (M+NH4) <sup>+</sup> . [0160] Step-4: Synthesis of 5-[3-[2-[2-[2-(2- azidoethoxy)ethoxy]ethoxy]ethoxy]propyl]-2-(2,6-dioxo-3-pipe ridyl)isoindoline-1,3-dione (azide-10): A stirred mixture of 2-[2-[2-[2-[3-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindoli n-5- yl]propoxy]ethoxy]ethoxy]ethoxy]ethyl 4-methylbenzenesulfonate (azide-10-B`) (250 mg, 0.390 mmol) in DMF (2 mL) was added NaN3 (125.64 mg, 1.93 mmol) at 0 °C, the reaction was allowed to warm to room temperature and stirred at 90 °C for 3 h. The reaction was evaporated in vacuo and the crude was taken in DCM (250 mL) and the organic layer was washed with water (2 x200 mL) and sat. brine solution (1 x 200 mL). The organics layer was dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by Combiflash column chromatography (230- 400 mesh silica gel), eluting with 80% EtOAc in hexanes to give 5-[3-[2-[2-(2- azidoethoxy)ethoxy]ethoxy]propyl]-2-(2,6-dioxo-3-piperidyl)i soindoline-1,3-dione (azide-10) (90 mg, 0.190 mmol, 47.73% yield). LCMS-ESI (pos.) m/z: 518.2 (M+H) ⁺ . EXAMPLE 13 Synthetic scheme for azide-11: [0161] Step-1: Synthesis of 3-azidopropan-1-ol (azide-11-B): To a stirred solution of 3-bromopropan-1-ol (azide-11-A) (2000 mg, 14.39 mmol) in DMF (10 mL), NaN ₃ (3741.28 mg, 57.56 mmol) was added, and the reaction mixture was stirred at RT for 12 h. After completion of the reaction as monitored by TLC, the reaction mixture was poured into ice-cold water and extracted with ethyl acetate (2 x 50 mL) and the combined organic layers were washed with brine. The organic layer was dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 25% ethyl acetate in hexanes to give 3-azidopropan-1-ol (azide-11-B) (880 mg, 8.703 mmol, 60.48% yield) as an yellow liquid. LCMS: Compound was not ionizable. [0162] Step-2: Synthesis of 3-azidopropyl 4-methylbenzenesulfonate (azide-11-C): To a stirred solution of 3-azidopropan-1-ol (azide-11-B) (880 mg, 8.7 mmol) in DCM (20 mL) at 0 °C was added triethyl amine (3.61 mL, 26.11 mmol), and p-toluenesulfonyl chloride (2488.95 mg, 13.06 mmol). The reaction was allowed to warm to RT and stirred at the same temperature for 12 h. The reaction was evaporated in vacuo and the residue was taken in DCM (100 mL) and the organic layer washed with water (2 x 20 mL) and sat. brine solution (1 x 20 mL). The organic layer was dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 40% EtOAc in hexanes to give 3- azidopropyl 4-methylbenzenesulfonate (azide-11-C) (1600 mg, 6.267 mmol, 72.01% yield). LCMS-ESI (pos.) m/z: 273.1 (M+NH4) ⁺ . [0163] Step-3: Synthesis of tert-butyl 4-(3-azidopropyl)piperazine-1-carboxylate (azide-11-D): To a stirred solution of tert-butyl piperazine-1-carboxylate (900 mg, 4.83 mmol), in MeCN (20 mL) at 0 °C were added potassium carbonate (1333.69 mg, 9.66 mmol) and 3-azidopropyl 4-methylbenzenesulfonate (azide-11-C) (1480.34 mg, 5.8 mmol). The reaction was allowed to warm to RT and stirred at 70 °C for 12 h. The reaction mixture was filtered through celite, and the filtrate was evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 20% EtOAc in hexanes to give tert-butyl 4-(3-azidopropyl)piperazine-1-carboxylate (azide-11-D) (920 mg, 3.416 mmol, 70.69% yield) LCMS: Compound was not ionizable. [0164] Step-4: Synthesis of 1-(3-azidopropyl)piperazine 2,2,2-trifluoroacetic acid (azide-11-E): To a stirred solution of tert-butyl 4-(3-azidopropyl)piperazine-1-carboxylate (azide- 11-D) (100 mg, 0.370 mmol) in hexafluoro-2-propanol (62.39 mg, 0.370 mmol) at 0 °C was added trifluoro acetic acid (0.14 mL, 1.86 mmol). The reaction was allowed to warm to RT and stirred at RT for 2 h. The reaction was evaporated in vacuo and the residue was triturated with pentane and dried in vacuo to give 1-(3-azidopropyl)piperazine 2,2,2-trifluoroacetic acid (azide-11-E) (60 mg, 0.212 mmol, 57.05% yield). LCMS: Compound was not ionizable. [0165] Step-5: Synthesis of 4-[4-(3-azidopropyl)piperazin-1-yl]-2-(2,6-dioxo-3- piperidyl)isoindoline-1,3-dione (azide-11):To a stirred solution of 1-(3-azidopropyl)piperazine 2,2,2-trifluoroacetic acid (azide-11-E) (451.2 mg, 1.59 mmol) in DMA (5 mL) was added DIPEA (0.91 mL, 5.07 mmol) followed by 2-(2,6-dioxo-3-piperidyl)-4-fluoro-isoindoline-1,3-dione (400 mg, 1.45 mmol). The reaction was stirred at 70 °C for 6 h. The reaction was poured into ice-water and extracted with EtOAc (2 x 50 mL). The combined organic layers were washed with water (2 x 10 mL) and sat. brine solution (1 x 10 mL). The organic layer was dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by neutral alumina eluting with 80% EtOAc in hexanes to give 4-[4-(3-azidopropyl)piperazin-1-yl]-2-(2,6-dioxo-3-piperidyl )isoindoline-1,3- dione (azide-11) (95 mg, 0.223 mmol, 15.42% yield). LCMS-ESI (pos.) m/z: 426.2 (M+H) ⁺ . EXAMPLE 14 Synthetic scheme for azide-12: [0166] Step-1: Synthesis of 2-(2,6-dioxo-3-piperidyl)-5-(8-hydroxyoct-1- ynyl)isoindoline-1,3-dione (azide-12-A): To a stirred solution of 5-bromo-2-(2,6-dioxo-3- piperidyl)isoindoline-1,3-dione (500 mg, 1.48 mmol) in THF (3 mL) were added oct-7-yn-1-ol (243.32 mg, 1.93 mmol), and DIPEA (1.33 mL, 7.42 mmol) and degassed for 30 min. using N2. Thereafter PdCl ₂ (PPh ₃ ) ₂ (155.95 mg, 0.220 mmol), and CuI (24.96 mg, 0.220 mmol) were added, and the reaction mixture was heated for 16 h at 90 °C. THF was evaporated, and the residue was extracted with EtOAc and water. The organic layer was separated and evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 76 % EtOAc in hexanes to give 2-(2,6-dioxo-3-piperidyl)-5-(8-hydroxyoct-1-ynyl)isoindoline - 1,3-dione (azide-12-A) (230 mg, 0.601 mmol, 40.55% yield). LCMS-ESI (pos.) m/z: 382.8 (M+H) ⁺ . [0167] Step-2: Synthesis of 2-(2,6-dioxo-3-piperidyl)-5-(8-hydroxyoctyl)isoindoline- 1,3-dione (azide-12-B): To a stirred solution of 2-(2,6-dioxo-3-piperidyl)-5-(8-hydroxyoct-1- ynyl)isoindoline-1,3-dione (azide-12-A) (230 mg, 0.600 mmol) in ethanol (3 mL) were added 10% Pd-C (230 mg, 2.17 mmol) (wet) and stirred for 3 h at RT under H2 balloon atmosphere. Reaction mixture was filtered, and the filtrate was evaporated in vacuo. The crude product was triturated with pentane and dried in vacuo to give 2-(2,6-dioxo-3-piperidyl)-5-(8-hydroxyoctyl)isoindoline- 1,3-dione (azide-12-B) (100 mg, 0.259 mmol, 43.03% yield). LCMS-ESI (pos.) m/z: 387.0 (M+H) ⁺ . [0168] Step-3: Synthesis of 8-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-5- yl]octyl 4-methylbenzenesulfonate (azide-12-C): To a stirred solution of 2-(2,6-dioxo-3- piperidyl)-5-(8-hydroxyoctyl)isoindoline-1,3-dione (azide-12-B) (200 mg, 0.520 mmol) in DCM (3 mL) was added TsCl (197.34 mg, 1.04 mmol) and trimethylamine (0.22 mL, 1.55 mmol) and stirred at RT for 16 h. The reaction mixture was diluted with EtOAc and washed with water. The organic layer was evaporated in vacuo and the crude was purified by Combiflash column chromatography (230-400 mesh silica gel) eluting with 30% EtOAc in hexane to give 8-[2-(2,6- dioxo-3-piperidyl)-1,3-dioxo-isoindolin-5-yl]octyl 4-methylbenzenesulfonate (azide-12-C) (86 mg, 0.16 mmol, 30% yield). LCMS-ESI (pos.) m/z: 541.3 (M+H) ⁺ . [0169] Step-4: Synthesis of 5-(8-azidooctyl)-2-(2,6-dioxo-3-piperidyl)isoindoline-1,3- dione (azide-12): To a stirred solution of 8-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-5- yl]octyl 4-methylbenzenesulfonate (azide-12-C) (100 mg, 0.180 mmol) in DMF (2 mL) were added sodium azide (93.41 mg, 0.920 mmol) at 0 °C and stirred at RT for 16 h. The reaction mixture was diluted in EtOAc and washed with cold water. The organic layer was dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel) eluting with 70% EtOAc-hexanes to give 5-(8- azidooctyl)-2-(2,6-dioxo-3-piperidyl)isoindoline-1,3-dione (azide-12) (60 mg, 0.144 mmol, 78% yield). LCMS-ESI (pos.) m/z: 412.0 (M+H) ⁺ . EXAMPLE 15 Synthetic scheme for azide-13: [0170] Step-1: Synthesis of 2-(2,6-dioxo-3-piperidyl)-5-(6-hydroxyhex-1- ynyl)isoindoline-1,3-dione (azide-13-A): To a stirred solution of 5-bromo-2-(2,6-dioxo-3- piperidyl)isoindoline-1,3-dione [26166-92-7] (300 mg, 0.890 mmol) and hex-5-yn-1-ol [928-90- 5] (azide-13-A1) (261.99 mg, 2.67 mmol) in THF (3 mL) was added DIPEA (638.97 uL, 3.56 mmol) and degassed for 15 min with argon. Thereafter were added copper iodide (50.72 mg, 0.270 mmol) and bis(triphenylphosphine)palladium(II) dichloride (93.69 mg, 0.130 mmol) and the reaction mixture was purged again for 3-5 min using argon and then stirred for 16 h at 70°C. The reaction mixture was filtered through a celite pad and washed with ethyl acetate The filtrate was evaporated in vacuo. The crude was purified through Combiflash column chromatography (230- 400 mesh silica gel), eluting with 3.5-4% MeOH in DCM to give 2-(2,6-dioxo-3-piperidyl)-5-(6- hydroxyhex-1-ynyl)isoindoline-1,3-dione (azide-13-A) (170 mg, 0.479 mmol, 53.91% yield) as a brown solid. LCMS-ESI (pos.) m/z: 355.0 (M+H) ⁺ . [0171] Step-2: Synthesis of 2-(2,6-dioxo-3-piperidyl)-5-(6-hydroxyhexyl)isoindoline- 1,3-dione (azide-13-B): To the stirred solution of 2-(2,6-dioxo-3-piperidyl)-5-(6-hydroxyhex-1- ynyl)isoindoline-1,3-dione (azide-13-A) (210 mg, 0.590 mmol) in ethanol (4 mL) was added Pd/C (210 mg, 100% w/w) at RT and the reaction mixture was stirred for 2 h under H2 atmosphere using balloon. The reaction mixture was filtered through a celite pad. The filtrate was evaporated in vacuo and the crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 2.5%-3% MeOH in DCM to give 2-(2,6-dioxo-3-piperidyl)-5-(6- hydroxyhexyl)isoindoline-1,3-dione (azide-13-B) (150 mg, 0.419 mmol, 70.63% yield) as brown color solid. LCMS-ESI (pos.) m/z: 359.2 (M+H) ⁺ . [0172] Step-3: Synthesis of 6-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-5- yl]hexyl 4-methylbenzenesulfonate (azide-13-C): To the stirred solution of 2-(2,6-dioxo-3- piperidyl)-5-(5-hydroxypentyl)isoindoline-1,3-dione (azide-13-B) (50 mg, 0.150 mmol) in DCM (5 mL) under N2 atmosphere at 0 °C was added triethyl amine (80.36 uL, 0.580 mmol) and after 5 min p-toluenesulfonyl chloride (41.52 mg, 0.2200mmol) was added and the reaction mixture was stirred for 16 h at RT. The reaction mixture was diluted with water (5 mL) and extracted with DCM (25 mL). The organic layer was dried with anhydrous Na ₂ SO ₄ and concentrated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel) eluting with at 1.2% MeOH in DCM to give 6-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-5-yl]hexyl 4-methylbenzenesulfonate (azide-13-C) (150 mg, 0.293 mmol, 69.92% yield) as pale brown color solid. LCMS-ESI (pos.) m/z: 513.2 (M+H) ⁺ . [0173] Step-4: Synthesis of 5-(6-azidohexyl)-2-(2,6-dioxo-3-piperidyl)isoindoline- 1,3-dione (azide-13): To a stirred solution of 6-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-5- yl]hexyl 4-methylbenzenesulfonate (azide-13-B) (130 mg, 0.250 mmol) in DMF (2 mL) was added NaN ₃ (82.43 mg, 1.27 mmol) and the reaction mixture was stirred at 90 °C for 2 h, The reaction mixture was evaporated in vacuo and the residue was taken in DCM (50 mL). The organic layer was washed with water (2 x 20 mL) and sat. brine solution (1 x 20 mL). The organic layer was separated and dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel) eluting with 80% EtOAc in hexanes to give 5-(6-azidohexyl)-2-(2,6-dioxo-3-piperidyl)isoindoline-1,3-di one (azide-13) (60 mg, 0.156 mmol, 61.70% yield). LCMS-ESI (neg.) m/z: 382.2 (M-H)-.

EXAMPLE 16 Synthetic scheme for azide-14: [0174] Step-1: Synthesis of 2-(2,6-dioxo-3-piperidyl)-5-(12-hydroxydodec-1- ynyl)isoindoline-1,3-dione (azide-14-A): To a stirred solution of 5-bromo-2-(2,6-dioxo-3- piperidyl)isoindoline-1,3-dione [1418209-88-7] (750 mg, 2.22 mmol) in THF (3 mL) were added dodec-11-yn-1-ol (azide-14-A1) (527.22 mg, 2.89 mmol) and DIPEA (1.6 mL, 8.9 mmol) and degassed for 30 min using N2. Then PdCl2(PPh3)2 (233.92 mg, 0.330 mmol), and CuI (37.44 mg, 0.330 mmol) were added, and the reaction mixture was heated at 90 °C for 16 h. The reaction mixture was evaporated in vacuo and the residue was taken in EtOAc (30 mL) and washed with water (20 mL x 3). The organic layer was dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude residue was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 80% EtOAc in hexanes to give 2-(2,6-dioxo-3-piperidyl)-5-(12-hydroxydodec-1- ynyl)isoindoline-1,3-dione (azide-14-A) (350 mg, 0.798 mmol, 35.88% yield). LCMS-ESI (pos.) m/z: 439.2 (M+H) ⁺ . [0175] Step-2: Synthesis of 2-(2,6-dioxopiperidin-3-yl)-5-(12- hydroxydodecyl)isoindoline-1,3-dione (azide-14-B): To a stirred solution of 2-(2,6-dioxo-3- piperidyl)-5-(8-hydroxyoct-1-ynyl)isoindoline-1,3-dione (azide-14-A) (230 mg, 0.600 mmol) in ethanol (3 mL) were added 10% Pd-C (230 mg, 2.17 mmol) and stirred it for 3 h at RT under H2 balloon atmosphere. Progress of the reaction was monitored by LCMS and TLC (5% MeOH in DCM). Reaction mixture was filtered, and the filtrate was evaporated in vacuo. The crude product was triturated with n-pentane and dried in vacuo to give 2-(2,6-dioxo-3-piperidyl)-5-(8- hydroxyoctyl)isoindoline-1,3-dione (azide-12B) (100 mg, 0.259 mmol, 43.03% yield). LCMS- ESI (pos.) m/z: 387.0 (M+H) ⁺ . [0176] Step-3: Synthesis of 12-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-5- yl]dodecyl 4-methylbenzenesulfonate (azide-14-C): To a stirred solution of 2-(2,6-dioxo-3- piperidyl)-5-(12-hydroxydodecyl)isoindoline-1,3-dione (azide-14-B) (30 mg, 0.070 mmol) in DCM (3 mL) were added TsCl (38.77 mg, 0.200 mmol) and triethylamine (38.04 uL, 0.270 mmol) and stirred at RT for 6 h. Progress of the reaction was monitored by TLC (30% EtOAc in hexanes). After completion of the reaction, the reaction mixture was diluted with water, and extracted by EtOAc. The organic layer was dried over anhydrous Na2SO4 and evaporated in vacuo to give 12- [2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-5-yl]dodecyl 4-methylbenzenesulfonate (azide- 14-C) (50 mg crude). The crude product was directly used for next step, confirmed based on TLC only. [0177] Step-4: Synthesis of 5-(12-azidododecyl)-2-(2,6-dioxo-3- piperidyl)isoindoline-1,3-dione (azide-14): To a stirred solution of 8-[2-(2,6-dioxo-3-piperidyl)- 1,3-dioxo-isoindolin-5-yl]octyl 4-methylbenzenesulfonate (azide-14-C) (50 mg, 0.090 mmol) in DMF (1 mL) was added sodium azide (46.7 mg, 0.460 mmol) at 0 °C and stirred at 70 °C for 16 h. The reaction mixture was diluted in EtOAc and washed with cold water. The organic layer was dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 40% EtOAc in hexane to give 5- (12-azidododecyl)-2-(2,6-dioxo-3-piperidyl)isoindoline-1,3-d ione (azide-14) (10 mg, 0.021 mmol, 25.53% yield). LCMS-ESI (neg.) m/z: 466.3 (M-H)-. EXAMPLE 17 Preparation of Compounds According to Procedure A: [0178] Additional compounds were prepared according to Procedure A starting from alkyne-1 and a variety of azides. Their preparation is summarized in Table 1 below. Table 1: Compounds prepared via alkyne and azide cyclization according to Procedure A EXAMPLE 18 Synthesis of 4-[2-[2-[2-[4-[4-[[6-(6-aminopyrazin-2-yl)imidazo[1,2-a]pyra zin-8- yl]amino]phenyl]piperazin-1-yl]-2-oxo-ethoxy]ethoxy]ethylami no]-2-(2,6-dioxo-3- piperidyl)isoindoline-1,3-dione (126) [0179] 4-[2-[2-[2-[4-[4-[[6-(6-aminopyrazin-2-yl)imidazo[1,2-a]pyra zin-8- yl]amino]phenyl]piperazin-1-yl]-2-oxo-ethoxy]ethoxy]ethylami no]-2-(2,6-dioxo-3- piperidyl)isoindoline-1,3-dione (126) may be prepared via the reaction of amine-1 and carboxylic acid-1 according to Procedure B shown in Scheme B below. Scheme B [0180] To a stirred solution of 2-[2-[2-[[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo- isoindolin-4-yl]amino]ethoxy]ethoxy]acetic acid (carboxylic acid-1) (30 mg, 0.070 mmol) in DMF (1 mL) at 0 °C, HATU (32.64 mg, 0.090 mmol) was added and the reaction mixture was stirred for 15 min. at 0 °C. Then 6-(6-aminopyrazin-2-yl)-N-(4-piperazin-1- ylphenyl)imidazo[1,2-a]pyrazin-8-amine dihydrochloride (amine-1) (42.81 mg, 0.090 mmol) and DIPEA (0.05mL, 0.290 mmol) was added to the reaction mixture and the stirring was continued for overnight at RT. After completion of the reaction, as monitored by LCMS, the reaction mixture was poured into ice-cold water and extracted with ethyl acetate and washed with brine. The organic layer was dried over anhydrous Na ₂ SO ₄ and concentrated in vacuo to give the crude. The crude was purified by prep-HPLC to give 4-[2-[2-[2-[4-[4-[[6-(6-aminopyrazin-2- yl)imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]piperazin-1-yl]-2 -oxo-ethoxy]ethoxy]ethylamino]- 2-(2,6-dioxo-3-piperidyl)isoindoline-1,3-dione (126)(20 mg, 0.025 mmol, 35% yield) as an yellow solid. ¹ H NMR (400 MHz, 100 °C DMSO-d ₆ ) δ 10.71 (s, 1H), 9.01 (s, 1H), 8.61 (s, 1H), 8.53 (s, 1H), 8.06 (s, 1H), 7.97 – 7.88 (m, 3H), 7.64 – 7.53 (m, 2H), 7.13 (d, J = 8.6 Hz, 1H), 7.01 (dd, J = 7.9, 18.6 Hz, 3H), 6.54 (t, J = 5.9 Hz, 1H), 6.11 (s, 2H), 5.00 (dd, J = 5.5, 12.4 Hz, 1H), 4.20 (s, 2H), 3.70 (t, J = 5.4 Hz, 3H), 3.65 (s, 3H), 3.62 (t, J = 5.2 Hz, 4H), 3.50 (q, J = 5.6 Hz, 2H), 3.15 (t, J = 5.2 Hz, 4H), 2.93 – 2.79 (m, 1H), 2.67 – 2.52 (m, 2H), 2.12 – 2.00 (m, 1H). LCMS-ESI (pos.) m/z: 789.40 (M+H) ⁺ . EXAMPLE 19 Synthetic scheme for amine-1: [0181] To a stirred solution of crude tert-butyl N-[6-[6-[bis(tert- butoxycarbonyl)amino]pyrazin-2-yl]imidazo[1,2-a]pyrazin-8-yl ]-N-(4-piperazin-1- ylphenyl)carbamate (amine-1A) (170 mg, 0.220 mmol) in 1,4-dioxane (0.500 mL) at 0 °C, HCl (4M) in dioxane (0.01 mL, 0.220 mmol) was added and the reaction mixture was stirred for 30 min at 0 °C. Then the stirring was continued for overnight at RT. After completion of the reaction, as monitored by LCMS, solvent and excess HCl was removed under reduced pressure and the crude was triturated with n-pentane to give crude 6-(6-aminopyrazin-2-yl)-N-(4-piperazin-1- ylphenyl)imidazo[1,2-a]pyrazin-8-amine dihydrochloride (amine-1) (95 mg, 0.206 mmol, 95.6% yield) as an yellow solid. The crude was almost pure and used in the next step without further purification. LCMS-ESI (pos.) m/z: 387.8 (M+H) ⁺ (Mass of free amine). EXAMPLE 20 Synthetic scheme for carboxylic acid-1: [0182] Step-1: Synthesis of tert-butyl 2-[2-[2-[[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo- isoindolin-4-yl]amino]ethoxy]ethoxy]acetate (carboxylic acid-1A): To a stirred solution of 2- (2,6-dioxo-3-piperidyl)-4-fluoro-isoindoline-1,3-dione (600 mg, 2.17 mmol) in DMA (6 mL), tert- butyl 2-[2-(2-aminoethoxy)ethoxy]acetate [2098500-69-50] (571.58 mg, 2.61 mmol), and DIPEA (1.17 mL, 6.52 mmol) were added and stirred for 16 h at 90 °C. The reaction mixture was quenched with ice cold water and extracted with EtOAc (50 mL x 2). The combined organic layers were washed with sat. brine solution (50 mL x 1). The organic layer was dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by Combiflash column chromatography (230- 400 mesh silica gel), eluting with 50% EtOAc in hexanes to give tert-butyl 2-[2-[2-[[2-(2,6-dioxo- 3-piperidyl)-1,3-dioxo-isoindolin-4-yl]amino]ethoxy]ethoxy]a cetate (carboxylic acid-1A) (450 mg, 0.946 mmol, 43.57% yield) as a bright yellow solid. LCMS-ESI (pos.) m/z: 476.5(M+H) ⁺ . [0183] Step-2: Synthesis of 2-[2-[2-[[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin- 4-yl]amino]ethoxy]ethoxy]acetic acid (carboxylic acid-1): To a stirred solution of tert-butyl 2-[2- [2-[[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-4-yl]ami no]ethoxy]ethoxy]acetate (carboxylic acid-1A) (450 mg, 0.950 mmol) in DCM (2.614 mL) at 0 °C was added TFA (0.85 mL, 4.73 mmol). The reaction was allowed to warm to RT and stirred for 3 h. The solvents was evaporated in vacuo and the crude was triturated with n-pentane to give 2-[2-[2-[[2-(2,6-dioxo-3- piperidyl)-1,3-dioxo-isoindolin-4-yl]amino]ethoxy]ethoxy]ace tic acid (carboxylic acid-1) (230 mg, 0.548 mmol, 57.95% yield) as an off-white solid. LCMS-ESI (pos.) m/z: 420.4(M+H) ⁺ . EXAMPLE 21 Synthetic scheme for amine-2: [0184] Step-1: Synthesis of tert-butyl 4-[4-[4-[[6-[6-[bis(tert- butoxycarbonyl)amino]pyrazin-2-yl]imidazo[1,2-a]pyrazin-8-yl ]-tert-butoxycarbonyl- amino]phenyl]piperazin-1-yl]piperidine-1-carboxylate (amine-2A): To a stirred solution of tert- butyl 4-oxopiperidine-1-carboxylate (199.89 mg, 1 mmol) and AcOH (0.038 mL, 0.670 mmol) in DCE (10 mL), tert-butyl N-[6-[6-[bis(tert-butoxycarbonyl)amino]pyrazin-2-yl]imidazo[ 1,2- a]pyrazin-8-yl]-N-(4-piperazin-1-ylphenyl)carbamate (460 mg, 0.670 mmol) was added and the reaction mixture was stirred for 1 h at RT. Then Sodium triacetoxyborohydride (850.32 mg, 4.01 mmol) was added and the overall reaction mixture was stirred for overnight at RT. After completion of the reaction, as monitored by LCMS, the reaction mixture was diluted with DCM and washed with water, dried over anhydrous Na ₂ SO ₄ , and concentrated in vacuo to give the crude. The crude was purified by Combiflash column chromatography using 5% MeOH in DCM to give tert-butyl 4-[4-[4-[[6-[6-[bis(tert-butoxycarbonyl)amino]pyrazin-2-yl]i midazo[1,2- a]pyrazin-8-yl]-tert-butoxycarbonyl-amino]phenyl]piperazin-1 -yl]piperidine-1-carboxylate (amine-2A) (400 mg, 0.459 mmol, 68.66 % yield) as an yellow sticky solid. LCMS-ESI (pos.) m/z: 871.4 (M+H) ⁺ . [0185] Step-2: Synthesis of 6-(6-aminopyrazin-2-yl)-N-[4-[4-(4-piperidyl)piperazin- 1-yl]phenyl]imidazo[1,2-a]pyrazin-8-amine dihydrochloride (amine-2): To a stirred solution of tert-butyl 4-[4-[4-[[6-[6-[bis(tert-butoxycarbonyl)amino]pyrazin-2-yl]i midazo[1,2-a]pyrazin- 8-yl]-tert-butoxycarbonyl-amino]phenyl]piperazin-1-yl]piperi dine-1-carboxylate (390 mg, 0.450 mmol) in 1,4-dioxane (2 mL) at 0 °C, HCl (4M) in dioxane (0.015 mL, 0.450 mmol) was added and the overall reaction mixture was stirred for 30 min at 0 °C. Then the stirring was continued for overnight at RT. After completion of the reaction, as monitored by LCMS, solvent and excess HCl was removed under reduced pressure and the crude was triturated with n-pentane to give crude 6-(6-aminopyrazin-2-yl)-N-[4-[4-(4-piperidyl)piperazin-1-yl] phenyl]imidazo[1,2-a]pyrazin-8- amine dihydrochloride (amine-2) (230 mg, 0.423 mmol, 94.52% yield) as an yellow solid. The crude was used in the next step without further purification. LCMS-ESI (pos.) m/z: 471.3 (M+H) ⁺ (Mass of free amine). EXAMPLE 22 Synthetic scheme for amine-3: [0186] Step-1: Synthesis of tert-butyl N-[2-(N-methyl-4-nitro-anilino)ethyl]carbamate (amine-3-B): To the stirred solution of 1-fluoro-4-nitro-benzene (amine-3-A) [350-46-9] (500.mg, 3.54mmol) in DMF (4 mL) was added cesium carbonate (896.44 mg, 8.86 mmol) followed by tert-butyl N-[2-(methylamino)ethyl]carbamate [122734-32-1] (617.43 mg, 3.54 mmol) and the reaction was stirred for 16 h at 80 °C. The solvent was removed in vacuo to give the crude which was purified by Combiflash (230-400 mesh silica gel), eluting with 15% EtOAc in hexanes to give tert-butyl N-[2-(N-methyl-4-nitro-anilino)ethyl]carbamate (amine-3-B) (300 mg, 1.016 mmol, 28.67% yield) as an yellow solid. LCMS-ESI (pos.) m/z: 296.3 (M+H) ⁺ . [0187] Step-2: Synthesis of tert-butyl N-[2-(4-amino-N-methyl- anilino)ethyl]carbamate (amine-3-C): To the stirred solution of tert-butyl N-[2-(N-methyl-4-nitro- anilino)ethyl]carbamate (amine-3-B) (200 mg, 0.680 mmol) in methanol (2 mL) was added 10% Pd-C (200 mg, 100% w/w) and the reaction mixture was stirred for 2 h under H2 atmosphere using balloon pressure, Crude LCMS showed presence of the product mass, then the reaction mixture was filtered through celite pad and the celite was washed with (2x30 mL) EtOAc. The filtrate was evaporated in vacuo to give the crude tert-butyl N-[2-(4-amino-N-methyl-anilino)ethyl]carbamate (amine-3-C) (70 mg,0.264 mmol, 38.95% yield) as a black liquid which was used in next step without further purification. LCMS-ESI (pos.) m/z: 266.29 (M+H) ⁺ . [0188] Step-3: Synthesis of tert-butyl N-[2-[4-[(6-bromoimidazo[1,2-a]pyrazin-8- yl)amino]-N-methyl-anilino]ethyl]carbamate (amine-3-D): To a stirred solution of tert-butyl N- [2-(4-amino-N-methyl-anilino)ethyl]carbamate (amine-3-C) (200 mg, 0.750 mmol), 6,8- dibromoimidazo[1,2-a]pyrazine (229.59 mg, 0.830 mmol) in DMF (3 mL), DIPEA (0.34 mL, 1.88 mmol) was added and the reaction mixture was heated at 85 °C for overnight. After completion of the reaction as monitored by LCMS, the reaction mixture was poured into ice-cold water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous Na ₂ SO ₄ and concentrated in vacuo to give the crude which was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with at 70% EtOAc in hexanes to give tert-butyl N-[2-[4-[(6-bromoimidazo[1,2-a]pyrazin-8-yl)amino]-N-methyl- anilino]ethyl]carbamate (amine-3-D) (70 mg, 0.152 mmol, 20.13% yield) as an yellow solid. LCMS-ESI (pos.) m/z: 463.4 (M+H) ⁺ . [0189] Step-4: Synthesis of tert-butyl N-(6-bromoimidazo[1,2-a]pyrazin-8-yl)-N-[4- [2-(tert-butoxycarbonylamino)ethyl-methyl-amino]phenyl]carba mate (amine-3-E): To a stirred solution of tert-butyl N-[2-[4-[(6-bromoimidazo[1,2-a]pyrazin-8-yl)amino]-N-methyl- anilino]ethyl]carbamate (amine-3-D) (3000 mg, 6.5 mmol) in DCM (25 mL), DMAP (79.44 mg, 0.650 mmol) and Boc-anhydride (1.49 mL, 6.5 mmol) were added and the reaction mixture was heated at 65 °C for 3 h. After completion of the reaction as monitored by TLC, solvent was removed in vacuo and the crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 40% ethyl acetate in hexanes to give tert-butyl N-(6- bromoimidazo[1,2-a]pyrazin-8-yl)-N-[4-[2-(tert-butoxycarbony lamino)ethyl-methyl- amino]phenyl]carbamate (amine-3-E) (2800 mg, 4.987 mmol, 76.69% yield) (lower Rf in TLC) as a pale yellow solid and tert-butyl N-[4-[2-[bis(tert-butoxycarbonyl)amino]ethyl-methyl- amino]phenyl]-N-(6-bromoimidazo[1,2-a]pyrazin-8-yl)carbamate (amine-3-E1) (300 mg, 0.4535 mmol, 6.97% yield) (higher Rf in TLC) as a pale yellow solid LCMS-ESI (pos.) m/z: 563.2 (M+H) ⁺ for (amine-3-E), 661.2 (M+H) ⁺ for (amine-3-E1). [0190] Step-5: Synthesis of tert-butyl N-[6-[6-[bis(tert- butoxycarbonyl)amino]pyrazin-2-yl]imidazo[1,2-a]pyrazin-8-yl ]-N-[4-[2-(tert- butoxycarbonylamino)ethyl-methyl-amino]phenyl]carbamate (amine-3-F): In a sealed tube, to a degassed (for 15 min,) stirred solution of tert-butyl N-tert-butoxycarbonyl-N-[6-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazin-2-yl]carbamate (3001.41 mg, 7.12 mmol), Pd(PPh3)4 (205.81 mg, 0.180 mmol) and DME (80 mL, 11.52 mmol) in crude tert-butyl N-(6- bromoimidazo[1,2-a]pyrazin-8-yl)-N-[4-[2-(tert-butoxycarbony lamino)ethyl-methyl- amino]phenyl]carbamate (amine-3-E) (1000 mg, 1.78 mmol) and water (4 mL), was added Na2CO3 (566.37 mg, 5.34 mmol) and the mixture was further degassed for few min. using N2. Then the reaction mixture was heated at 90 °C for 12 h. The reaction was removed from heat and allowed to cool to RT. The reaction contents were filtered through celite and the filter cake was washed with EtOAc (150 mL). The filtrate was concentrated in vacuo to provide the crude which was purified by Combiflash column chromatography (using 230-400 mesh silica gel), eluting with 55% EtOAc in hexanes to give tert-butyl N-[6-[6-[bis(tert-butoxycarbonyl)amino]pyrazin-2- yl]imidazo[1,2-a]pyrazin-8-yl]-N-[4-[2-(tert-butoxycarbonyla mino)ethyl-methyl- amino]phenyl]carbamate amine-3-F (350 mg, 0.4511 mmol, 25.33% yield) as a pale yellow solid. LCMS-ESI (pos.) m/z: 776.1 (M+H) ⁺ . [0191] Step-6: Synthesis of N1-(2-aminoethyl)-N4-[6-(6-aminopyrazin-2- yl)imidazo[1,2-a]pyrazin-8-yl]-N1-methyl-benzene-1,4-diamine hydrochloride (amine-3): To a stirred solution of tert-butyl N-[6-[6-[bis(tert-butoxycarbonyl)amino]pyrazin-2-yl]imidazo[ 1,2- a]pyrazin-8-yl]-N-[4-[2-(tert-butoxycarbonylamino)ethyl-meth yl-amino]phenyl]carbamate (amine-3-F) (300 mg, 0.390 mmol) in 1,4-dioxane (3 mL) at 0 °C, HCl (4M) in dioxane (0.013 mL, 0.390 mmol) was added and the reaction mixture was stirred for 30 min at 0 °C. Then the stirring was continued for overnight at RT. After completion of the reaction as monitored by LCMS, solvent and excess HCl was removed in vacuo and the crude was triturated with n-pentane to give crude N1-(2-aminoethyl)-N4-[6-(6-aminopyrazin-2-yl)imidazo[1,2-a]p yrazin-8-yl]-N1- methyl-benzene-1,4-diamine hydrochloride (amine-3) (150 mg, 0.364 mmol, 94.2%yield) as an yellow solid. LCMS-ESI (pos.) m/z: 376.26 (M+H) ⁺ (Mass of free amine). EXAMPLE 23 Synthetic scheme for carboxylic acid-2: [0192] Step-1: Synthesis of tert-butyl 2-[[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo- isoindolin-4-yl]amino]acetate (carboxylic acid-2A): To a stirred solution of 2-(2,6-dioxo-3- piperidyl)-4-fluoro-isoindoline-1,3-dione [835616-60-9] (750 mg, 2.72 mmol) in DMA (22.5 mL) was added tert-butyl 2-aminoacetate [6456-74-2] (600.05 mg, 4.57 mmol) and DIPEA (11.25 mL, 64.59 mmol). The reaction mixture was stirred at 90 °C for 16 h in a sealed tube. The reaction mixture was poured in cold-water and extracted with EtOAc. The organic layer was washed with brine and dried over anhydrous Na ₂ SO ₄ . The crude was purified by Combiflash column chromatography (230-400 mesh silica gel) eluting with 30% EtOAc-hexanes to give tert-butyl 2- [[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-4-yl]amino] acetate (carboxylic acid-2A)(400 mg, 0.857 mmol, 31.56% yield). LCMS-ESI (pos.) m/z: 388.2 (M+H) ⁺ . [0193] Step-2: Synthesis of 2-[[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-4- yl]amino]acetic acid (carboxylic acid-2): To a stirred solution of tert-butyl 2-[[2-(2,6-dioxo-3- piperidyl)-1,3-dioxo-isoindolin-4-yl]amino]acetate (carboxylic acid-2A) (500 mg, 1.29 mmol) in DCM (10.7 mL) was added TFA (0.9 mL, 11.68 mmol) at 0 °C and stirred at RT for 16 h. The solvents were evaporated in vacuo and the crude was triturated with pentane to give 2-[[2-(2,6- dioxo-3-piperidyl)-1,3-dioxo-isoindolin-4-yl]amino]acetic acid (carboxylic acid-2) (350 mg, 0.771 mmol, 59.76% yield). LCMS-ESI (pos.) m/z: 332.1(M+H) ⁺ . EXAMPLE 24 Synthetic scheme for carboxylic acid-3: [0194] Step-1: Synthesis of tert-butyl 8-[[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo- isoindolin-4-yl]amino]octanoate (carboxylic acid-3A) To a stirred solution of 2-(2,6-dioxo-3- piperidyl)-4-fluoro-isoindoline-1,3-dione [835616-60-9] (750 mg, 2.72 mmol) in DMA (22.5 mL) was added tert-butyl 8-aminooctanoate [102522-32-7] (985.05 mg, 4.57 mmol) and DIPEA (11.25 mL, 64.59 mmol). The reaction mixture was stirred at 90 °C for 48 h in a sealed tube. The reaction mixture was poured in cold-water and extracted with EtOAc. The organic layer was washed with brine and dried over anhydrous Na ₂ SO ₄ . The crude was purified by Combiflash column chromatography (230-400 mesh silica gel) eluting with 30% EtOAc-hexanes to give tert- butyl 8-[[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-4-yl]amin o]octanoate (carboxylic acid- 3A) (700 mg, 1.4548 mmol, 53.58% yield). LCMS-ESI (pos.) m/z: 472.4(M+H) ⁺ . [0195] Step-2: Synthesis of 8-[[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-4- yl]amino]octanoic acid (carboxylic acid-3) To a stirred solution of tert-butyl 8-[[2-(2,6-dioxo-3- piperidyl)-1,3-dioxo-isoindolin-4-yl]amino]octanoate (carboxylic acid-3A)(700 mg, 1.48 mmol) in DCM (2 mL) was added TFA (0.8 mL, 5.05 mmol) at 0 °C and stirred at RT for 3 h. The solvents were evaporated in vacuo and the crude residue was triturated with pentane to give 8-[[2-(2,6- dioxo-3-piperidyl)-1,3-dioxo-isoindolin-4-yl]amino]octanoic acid (carboxylic acid-3) (450 mg,0.953 mmol, 64.21% yield). LCMS-ESI (pos.) m/z: 415.8(M+H) ⁺ .

EXAMPLE 25 Synthetic scheme for carboxylic acid-4: [0196] Step-1: Synthesis of tert-butyl tert-butyl 2-[2-[2-[2-[2-[[2-(2,6-dioxo-3- piperidyl)-1,3-dioxo-isoindolin-4-yl]amino]ethoxy]ethoxy]eth oxy]ethoxy]acetate (carboxylic acid-4A): To a stirred solution of 2-(2,6-dioxo-3-piperidyl)-4-fluoro-isoindoline-1,3-dione [835616-60-9] (600 mg, 2.17 mmol) in DMA (12 mL), tert-butyl 2-[2-[2-[2-(2- aminoethoxy)ethoxy]ethoxy]ethoxy]acetate [864680-64-8] (801.22 mg, 2.61 mmol) and DIPEA (1.13 mL, 6.51 mmol) was added and stirred for 16 h at 90 °C. The reaction mixture was quenched with ice-cold water and extracted with EtOAc (50 mL x 2). The combined organic layers were washed with sat. brine solution (50 mL x 1). The organic layer was dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 70% EtOAc in hexanes to give tert-butyl 2-[2-[2-[2-[2-[[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindol in-4- yl]amino]ethoxy]ethoxy]ethoxy]ethoxy]acetate (carboxylic acid-4A) (480 mg, 0.8517 mmol, 39.21% yield) as a bright yellow solid. LCMS-ESI (pos.) m/z: 564.2 (M+H) ⁺ . [0197] Step-2: Synthesis of 2-[2-[2-[2-[2-[[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo- isoindolin-4-yl]amino]ethoxy]ethoxy]ethoxy]ethoxy]acetic acid (carboxylic acid-4): To a stirred solution of tert-butyl 2-[2-[2-[2-[2-[[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindol in-4- yl]amino]ethoxy]ethoxy]ethoxy]ethoxy]acetate (carboxylic acid-4A) (480 mg, 0.850 mmol) in DCM (4.7 mL) at 0 °C was added TFA (0.33 mL, 4.26 mmol). The reaction mixture was stirred at RT for 3 h. The solvents were evaporated in vacuo and the crude was triturated with n-pentane to give 2-[2-[2-[2-[2-[[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindol in-4- yl]amino]ethoxy]ethoxy]ethoxy]ethoxy]acetic acid (carboxylic acid-4) (270 mg, 0.532 mmol, 62.47% yield) as an yellow solid. LCMS-ESI (pos.) m/z: 508.5 (M+H) ⁺ . EXAMPLE 26 Synthetic scheme for carboxylic acid-5: [0198] Step-1: Synthesis of tert-butyl 2-[2-(p-tolylsulfonyloxy)ethoxy]acetate (carboxylic acid-5B): To a stirred solution of tert-butyl 2-(2-hydroxyethoxy)acetate (carboxylic acid-5A) (300 mg, 1.7 mmol) in DCM (1.5 mL) were added TsCl (649.17 mg, 3.41 mmol), and triethylamine (0.72 mL, 5.11 mmol) at RT and continued stirring for 16 h. The reaction mixture was diluted with DCM and washed with sat. NaHCO ₃ solution followed by water and brine. The organic layer was dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude product was purified by Combiflash column chromatography (230-400 mesh silica gel) eluting with 20% EtOAc in hexanes to give tert-butyl 2-[2-(p-tolylsulfonyloxy)ethoxy]acetate (carboxylic acid-5B) (400 mg,1.211 mmol, 71.11% yield). LCMS-ESI (pos.) m/z: 347.9 (M+NH4) ⁺ . [0199] Step-2: Synthesis of tert-butyl 2-[2-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo- isoindolin-4-yl]oxyethoxy]acetate (carboxylic acid-5C): To a stirred solution of tert-butyl 2-[2- (p-tolylsulfonyloxy)ethoxy]acetate (carboxylic acid-5B) (400 mg, 1.21 mmol) in DMF (2.5 mL) were added NaHCO3 (203.39 mg, 2.42 mmol), KI (40.19 mg, 0.240 mmol), 2-(2,6-dioxo-3- piperidyl)-4-hydroxy-isoindoline-1,3-dione (431.6 mg, 1.57 mmol) and stirred at 90 °C for 16 h.The reaction mixture was poured in cold-water and extracted with EtOAc. The organic layer was washed with water and brine, dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 30% EtOAc-hexanes to give tert-butyl 2-[2-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-4- yl]oxyethoxy]acetate (carboxylic acid-5C) (240 mg, 0.555 mmol, 45.84% yield). LCMS-ESI (pos.) m/z: 450.4(M+NH ₄ ) ⁺ . [0200] Step-3: Synthesis of 2-[2-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-4- yl]oxyethoxy]acetic acid (carboxylic acid-5): To a stirred solution of tert-butyl 2-[2-[2-(2,6- dioxo-3-piperidyl)-1,3-dioxo-isoindolin-4-yl]oxyethoxy]aceta te (carboxylic acid-5C) (240 mg, 0.560 mmol) in DCM (2.5 mL) cooled to 0 °C was added TFA (0.13 mL, 0.830 mmol). The reaction was allowed to warm to RT and stirred for 4 h. The reaction mixture was evaporated in vacuo and triturated with pentane to give 2-[2-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-4- yl]oxyethoxy]acetic acid (carboxylic acid-5) (180 mg, 0.431 mmol, 77.56% yield). LCMS-ESI (pos.) m/z: 377.1 (M+H) ⁺ . EXAMPLE 27 Synthetic scheme for carboxylic acid-6: [0201] Step-1: Synthesis of tert-butyl 2-[2-[2-[2-[[2-(2,6-dioxo-3-piperidyl)-1,3- dioxo-isoindolin-4-yl]amino]ethoxy]ethoxy]ethoxy]acetate (carboxylic acid-6A): To a stirred solution of 2-(2,6-dioxo-3-piperidyl)-4-fluoro-isoindoline-1,3-dione (600 mg, 2.17 mmol) in DMA (10 mL), tert-butyl 2-[2-[2-(2-aminoethoxy)ethoxy]ethoxy]acetate [189808-70-6] (686.4 mg, 2.61mmol) was added and stirred for 16 h at 90 °C. The reaction mixture was quenched with ice-cold water and extracted with EtOAc (50 mL x 2). The combined organic layers were washed with sat. brine solution (50 mL x 1). The organic layer was dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by Combiflash column chromatography (230- 400 mesh silica gel), eluting with 50% EtOAc in hexanes to give tert-butyl 2-[2-[2-[2-[[2-(2,6- dioxo-3-piperidyl)-1,3-dioxo-isoindolin-4-yl]amino]ethoxy]et hoxy]ethoxy]acetate (carboxylic acid-6A) (400 mg, 0.769 mmol, 35.44% yield) as a bright yellow solid. LCMS-ESI (pos.) m/z: 520.1 (M+H) ⁺ . [0202] Step-2: Synthesis of 2-[2-[2-[2-[[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo- isoindolin-4-yl]amino]ethoxy]ethoxy]ethoxy]acetic acid (carboxylic acid-6): To a stirred solution of tert-butyl 2-[2-[2-[2-[[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin- 4- yl]amino]ethoxy]ethoxy]ethoxy]acetate (carboxylic acid-6A) (400 mg, 0.770 mmol) in DCM (3 mL) cooled to 0 °C was added TFA (0.3 mL, 3.85 mmol). The reaction mixture was stirred at RT for 3 h. The solvents were evaporated in vacuo and the crude was triturated with n-pentane to give 2-[2-[2-[2-[[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin- 4- yl]amino]ethoxy]ethoxy]ethoxy]acetic acid (carboxylic acid-6) (250 mg, 0.539 mmol, 70.06% yield) as a yellow solid. LCMS-ESI (pos.) m/z: 464.1 (M+H) ⁺ . EXAMPLE 28 Synthetic scheme for carboxylic acid-7: [0203] Step-1: Synthesis of tert-butyl 5-(p-tolylsulfonyloxy)pentanoate (carboxylic acid-7B): To a stirred solution of 4-toluenesulfonyl chloride (547.09 mg, 2.87 mmol) in dry DCM (5 mL), triethylamine (0.6 mL, 4.3 mmol) and was added and stirred at RT. Then tert-butyl 5- hydroxypentanoate [91420-49-4] (carboxylic acid-7A) (250 mg, 1.43 mmol) was added and the reaction mixture was stirred at RT for 16 h. The solvents were evaporated in vacuo and the crude was extracted with EtOAc (50 mL x 2) and washed with water (50 mL x 2). The organic layer was dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel) eluting with 10% EtOAc in hexanes to give tert-butyl 5-(p-tolylsulfonyloxy)pentanoate (carboxylic acid-7B) (336 mg, 1.023 mmol, 71.31% yield) as a colorless liquid. LCMS-ESI (pos.) m/z: 329.3 (M+H) ⁺ . [0204] Step-2: Synthesis of tert-butyl 5-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo- isoindolin-4-yl]oxypentanoate (carboxylic acid-7C): To a stirred solution of 2-(2,6-dioxo-3- piperidyl)-4-hydroxy-isoindoline-1,3-dione (377.94 mg, 1.38 mmol) in dry DMF (10 mL), KI (16.98 mg, 0.100 mmol) and NaHCO3 (171.91 mg, 2.05 mmol) was added and stirred at RT for 15 min. Then tert-butyl 5-(p-tolylsulfonyloxy)pentanoate (carboxylic acid-7B) (336 mg, 1.02 mmol) was added and the reaction mixture was stirred at 90 °C for 3 h. The solvents were evaporated in vacuo and the crude residue was extracted with EtOAc (50 mL x 2) and washed with water (50 mL x 2). The organic layer was dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel) eluting with 50% EtOAc in hexanes to give tert-butyl 5-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin- 4-yl]oxypentanoate (carboxylic acid-7C) (90 mg, 0.209 mmol, 20.44% yield) as an white solid. LCMS-ESI (pos.) m/z: 431.2 (M+H) ⁺ . [0205] Step-3: Synthesis of 5-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-4- yl]oxypentanoic acid (carboxylic acid-7): To a stirred solution of tert-butyl 5-[2-(2,6-dioxo-3- piperidyl)-1,3-dioxo-isoindolin-4-yl]oxypentanoate (carboxylic acid-7-C) (92 mg, 0.210 mmol) in DCM (2 mL) cooled to 0 °C was added trifluoroacetic acid (0.52 mL, 6.84 mmol). The reaction was allowed to warm to RT and stirred at RT for 4 h. The reaction was evaporated in vacuo and the residue was triturated with n-pentane to give 5-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo- isoindolin-4-yl]oxypentanoic acid (carboxylic acid-7) (80 mg, 0.214 mmol, 99.99% yield). LCMS-ESI (pos.) m/z: 375.1(M+H) ⁺ .

EXAMPLE 29 Synthetic scheme for carboxylic acid-8: [0206] Step-1: Synthesis of tert-butyl 2-[2-[2-[2-(p- tolylsulfonyloxy)ethoxy]ethoxy]ethoxy]acetate (carboxylic acid-8-A): To a stirred solution of tert-butyl 2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]acetate [518044-31-0] (200 mg, 0.760 mmol), and triethylamine (0.32 mL, 2.27 mmol) in DCM (8 mL) at 0 °C was added Tosyl Chloride (288.53 mg, 1.51 mmol). The reaction was allowed to warm to RT and stirred at RT for 16 h. The reaction mixture was evaporated in vacuo and the crude was purified by Combi flash column chromatography (230-400 mesh silica gel) eluting with 20% EtOAc in hexanes to give tert-butyl 2-[2-[2-[2-(p-tolylsulfonyloxy)ethoxy]ethoxy]ethoxy]acetate (carboxylic acid-8-A) (27 7mg, 0.589 mmol, 77.85% yield). LCMS-ESI (pos.) m/z: 436.4 (M+NH4) ⁺ . [0207] Step-1A: Synthesis of 2-(2,6-dioxo-3-piperidyl)-4-hydroxy-isoindoline-1,3- dione (carboxylic acid-8-B): To a stirred solution of 4-hydroxyisobenzofuran-1,3-dione [37418- 88-5] (500 mg, 3.05 mmol) and 3-aminopiperidine-2,6-dione hydrochloride [24666-56-6] (651.9 mg, 3.96 mmol) in dry DMF (5 mL) was added DIPEA (0.58 mL, 3.35 mmol) at RT. Then the reaction mixture was heated at 90 °C for 16 h. After completion of reaction, solvents were evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel) eluting with 5% MeOH in DCM to give 2-(2,6-dioxo-3-piperidyl)-4-hydroxy- isoindoline-1,3-dione (carboxylic acid-8-B) (478 mg, 1.743 mmol, 57.21% yield). LCMS-ESI (pos.) m/z: 275.2 (M+H) ⁺ . [0208] Step-2: Synthesis of tert-butyl 2-[2-[2-[2-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo- isoindolin-4-yl]oxyethoxy]ethoxy]ethoxy]acetate (carboxylic acid-8-C): To a stirred solution of tert-butyl 2-[2-[2-[2-(p-tolylsulfonyloxy)ethoxy]ethoxy]ethoxy]acetate (carboxylic acid-8-A) (280 mg, 0.670 mmol), NaHCO ₃ (168.63 mg, 2.01 mmol), KI (11.11 mg, 0.070 mmol) in DMF (5 mL) at 0 °C was added 2-(2,6-dioxo-3-piperidyl)-4-hydroxy-isoindoline-1,3-dione (carboxylic acid-8-B) (275.21 mg, 1 mmol). The reaction was allowed to warm to room temperature and stirred at 90 °C for 16 h. The reaction was evaporated in vacuo and the resulting residue was taken up in EtOAc (30 mL). The organic layer was washed with water (2 x 10 mL) and sat. brine solution (1 x 10 mL). The organic layer was then separated and dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 5% MeOH in DCM to give tert-butyl 2-[2-[2-[2-[2-(2,6-dioxo-3-piperidyl)-1,3- dioxo-isoindolin-4-yl]oxyethoxy]ethoxy]ethoxy]acetate (carboxylic acid-8-C) (140 mg, 0.269 mmol, 40.2% yield). LCMS-ESI (pos.) m/z: 538.2 (M+NH4) ⁺ . [0209] Step-3: Synthesis of 2-[2-[2-[2-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo- isoindolin-4-yl]oxyethoxy]ethoxy]ethoxy]acetic acid (carboxylic acid-8): To a stirred solution of tert-butyl 2-[2-[2-[2-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-4 - yl]oxyethoxy]ethoxy]ethoxy]acetate (carboxylic acid-8-C) (130 mg, 0.250 mmol) in DCM (3 mL) cooled to 0 °C was added TFA (0.06 mL, 0.750 mmol). The reaction was allowed to warm to RT and stirred at RT for 3 h. The reaction mixture was evaporated in vacuo, and the crude was triturated with n-pentane to give 2-[2-[2-[2-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-4 - yl]oxyethoxy]ethoxy]ethoxy]acetic acid (carboxylic acid-8) (110 mg, 0.227 mmol, 91.05% yield). LCMS-ESI (neg.) m/z: 462.9 (M-H)-. EXAMPLE 30 Synthetic scheme for carboxylic acid-9: [0210] Step-1: Synthesis of methyl 9-(p-tolylsulfonyloxy)nonanoate (carboxylic acid- 9-C): To a stirred solution of methyl 9-hydroxynonanoate [34957-73-8] (400 mg, 2.12 mmol) in DCM (20 mL) at 0 °C, p-toluenesulfonyl chloride (810.16 mg, 4.25 mmol) and Et3N (1.19 mL, 8.5 mmol) was added, and the reaction mixture was stirred at 0 °C for 30 min. Then the reaction mixture was stirred overnight at RT. After completion of the reaction, water (10 mL) was added to the reaction mixture and extracted with DCM (30 mL). The organic layer was washed with brine and dried over anhydrous Na ₂ SO ₄ and concentrated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 10% EtOAc in hexanes to give methyl 9-(p-tolylsulfonyloxy)nonanoate (carboxylic acid-9-C) (560 mg,1.635 mmol, 76.96% yield) as a colorless sticky gum. LCMS-ESI (pos.) m/z: 343.1 (M+H) ⁺ . [0211] Step-2: Synthesis of 9-(p-tolylsulfonyloxy)nonanoic acid (carboxylic acid-9- D): To a stirred solution of methyl 9-(p-tolylsulfonyloxy)nonanoate (carboxylic acid-9-C) (560 mg, 1.64 mmol) in THF (7 mL) and water (1 mL), Lithium hydroxide monohydrate (137.23 mg, 3.27 mmol) was added and the reaction mixture was stirred for 4 h at RT. The THF were removed in vacuo and the reaction mixture was cooled to 0 °C and acidified with dilute HCl. Then the reaction mixture was extracted with DCM (2 x 30 mL). The organic layer was dried over anhydrous Na ₂ SO ₄ and concentrated in vacuo to give crude 9-(p-tolylsulfonyloxy)nonanoic acid (carboxylic acid-9-D) (370 mg, 1.127 mmol, 68.89% yield) as a colorless sticky gum. LCMS-ESI (pos.) m/z: 329.1 (M+H) ⁺ . [0212] Step-3: Synthesis of benzyl 9-(p-tolylsulfonyloxy)nonanoate (carboxylic acid- 9-E): To a stirred solution of 9-(p-tolylsulfonyloxy)nonanoic acid (carboxylic acid-9-D) (370 mg, 1.13 mmol) and K2CO3 (0.3 mL, 2.25 mmol) in acetone (10 mL), benzyl bromide (385.37 mg, 2.25 mmol) was added and the reaction mixture was stirred at RT for 16 h. After that, solvent was removed in vacuo and the residue was re-dissolved in EtOAc (15 mL). The organic layer was washed with brine, dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 30% EtOAc in hexanes to give benzyl 9-(p-tolylsulfonyloxy)nonanoate (carboxylic acid-9-E) (330 mg, 0.788 mmol, 69.98% yield) as a colorless sticky gum. LCMS-ESI (pos.) m/z: 419.0 (M+H) ⁺ . [0213] Step-4: Synthesis of benzyl 9-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin- 4-yl]oxynonanoate (carboxylic acid-9-F): To a stirred solution of benzyl 9-(p- tolylsulfonyloxy)nonanoate (carboxylic acid-9-E) (330 mg, 0.790 mmol) and 2-(2,6-dioxo-3- piperidyl)-4-hydroxy-isoindoline-1,3-dione (281.08 mg, 1.02 mmol) in DMA (5 mL), NaHCO3 (132.48 mg, 1.58 mmol) and KI (26.18 mg, 0.160 mmol) was added and the reaction mixture was heated at 95 °C for 4 h. Then the reaction mixture was cooled to RT and poured into ice-cold water and extracted with ethyl acetate (2 x 15 mL). The combined organic layers were dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 80% EtOAc in hexanes to give benzyl 9- [2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-4-yl]oxynona noate (carboxylic acid-9-F) (260 mg, 0.499 mmol, 63.35% yield) as an white solid. LCMS-ESI (pos.) m/z: 521.3 (M+H) ⁺ . [0214] Step-5: Synthesis of 9-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-4- yl]oxynonanoic acid (carboxylic acid-9): To a stirred solution of benzyl 9-[2-(2,6-dioxo-3- piperidyl)-1,3-dioxo-isoindolin-4-yl]oxynonanoate (carboxylic acid-9-F) (260 mg, 0.500 mmol) in EtOAc (10 mL) was added and 10% Pd-C (5 mg, 0.0500mmol). Then the reaction mixture was stirred under hydrogen atmosphere using a balloon for 4 h at RT. After completion of the reaction, the reaction mixture was filtered through a celite bed and the bed was washed with EtOAc. The filtrate was then concentrated in vacuo and the crude was triturated with n-pentane to give 9-[2- (2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-4-yl]oxynonanoi c acid (carboxylic acid-9) (150 mg, 0.348 mmol, 69.77 % yield) as a white solid. LCMS-ESI (pos.) m/z: 431.4 (M+H) ⁺ . EXAMPLE 31 Synthetic scheme for carboxylic acid-10: [0215] Step-1: Synthesis of tert-butyl 2-[2-[2-[2-[2-(p- tolylsulfonyloxy)ethoxy]ethoxy]ethoxy]ethoxy]acetate (carboxylic acid-10-A): To a stirred solution of tert-butyl 2-[2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethoxy]acetate (200 mg, 0.650 mmol) in DCM (4 mL) were added Et3N (0.27 mL, 1.95 mmol) and p-toluenesulfonyl chloride (136.02 mg, 0.710 mmol) successively. The reaction was allowed to stir at RT for 16 h. The reaction was evaporated in vacuo and the crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 35% EtOAc in hexane to give tert-butyl 2-[2-[2-[2-[2-(p-tolylsulfonyloxy)ethoxy]ethoxy]ethoxy]ethox y]acetate (carboxylic acid-10-A) (282.27 mg, 0.610 mmol, 94.09% yield) as a color less syrup. LCMS-ESI (pos.) m/z: 479.8 (M+NH ₄ ) ⁺ . [0216] Step-2: Synthesis of tert-butyl 2-[2-[2-[2-[2-[2-(2,6-dioxo-3-piperidyl)-1,3- dioxo-isoindolin-4-yl]oxyethoxy]ethoxy]ethoxy]ethoxy]acetate (carboxylic acid-10-B): To a stirred solution of 2-(2,6-dioxo-3-piperidyl)-4-hydroxy-isoindoline-1,3-dione (carboxylic acid-9- B) (200 mg, 0.730 mmol) in DMF (5 mL) were added tert-butyl 2-[2-[2-[2-[2-(p- tolylsulfonyloxy)ethoxy]ethoxy]ethoxy]ethoxy]acetate (carboxylic acid-10-A) (282.27 mg, 0.610 mmol), NaHCO ₃ (183.79 mg, 2.19 mmol), and KI (25.31 mg, 0.150 mmol) at RT in argon atmosphere and the reaction was stirred for 3 h at 90°C. The solvent was evaporated and the residue was diluted with cold water (10 mL) and extracted with EtOAc (2 x10 mL). the combined organic layers were dried over anhydrous Na ₂ SO ₄ , and evaporated in vacuo. The crude was purified by column chromatography (100-200 mesh silica gel) eluting with 70% EtOAc in hexane to give tert- butyl 2-[2-[2-[2-[2-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindoli n-4- yl]oxyethoxy]ethoxy]ethoxy]ethoxy]acetate (carboxylic acid-10-B) (120 mg, 0.212 mmol, 29.14% yield) as a yellow color gummy syrup. LCMS-ESI (pos.) m/z: 565.5 (M+H) ⁺ . [0217] Step-3: Synthesis of 2-[2-[2-[2-[2-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo- isoindolin-4-yl]oxyethoxy]ethoxy]ethoxy]ethoxy]acetic acid (carboxylic acid-10): To a stirred solution of tert-butyl 2-[2-[2-[2-[[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin- 5- yl]amino]ethoxy]ethoxy]ethoxy]acetate (carboxylic acid-10-B) (30 mg, 0.060 mmol) in dry DCM (0.600 mL) was added TFA (0.004 mL, 0.060 mmol) at 0 °C and the reaction mixture was stirred at RT for 3 h. After completion of the reaction, solvent and excess TFA were removed in vacuo. The crude was triturated with n-pentane (2 x 3 mL) and diethyl ether (2 x 3 mL) to give 2-[2-[2-[2-[[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin- 5- yl]amino]ethoxy]ethoxy]ethoxy]acetic acid (carboxylic acid-10) (20 mg, 0.043 mmol, 74.74% yield) as a brown sticky gummy liquid. LCMS-ESI (pos.) m/z: 509.3 (M+H) ⁺ . EXAMPLE 32 Synthetic scheme for carboxylic acid-11: [0218] Step-1: Synthesis of ethyl 8-(p-tolylsulfonyloxy)octanoate (carboxylic acid- 11-B): To a stirred solution of ethyl 8-hydroxyoctanoate [93892-06-9] (carboxylic acid-11-A) (400 mg, 2.12 mmol) in DCM (15 mL) at 0 °C, p-toluenesulfonyl chloride (810.16 mg, 4.25 mmol) and Et ₃ N (1.04 mL, 7.44 mmol) was added and the reaction mixture was stirred at 0 °C for 30 min. Then the reaction mixture was stirred overnight at RT. After completion of the reaction, water (10 mL) was added to the reaction mixture and extracted with DCM (30 mL). The organic layer was washed with brine and dried over anhydrous Na ₂ SO ₄ and concentrated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 10% EtOAc in hexanes to give ethyl 8-(p-tolylsulfonyloxy)octanoate (carboxylic acid-11-B) (410 mg,1.197 mmol, 56.35% yield) as a colorless sticky gum. LCMS-ESI (pos.) m/z: 343.0 (M+H) ⁺ . [0219] Step-2: Synthesis of 8-(p-tolylsulfonyloxy)octanoic acid (carboxylic acid-11- C): To a stirred solution of ethyl 8-(p-tolylsulfonyloxy)octanoate (carboxylic acid-11-B) (410 mg, 1.2 mmol) in THF (5 mL) and water (1 mL), lithium hydroxide monohydrate (100.47 mg, 2.39 mmol) was added and the reaction mixture was stirred for 4 h at RT. After completion of the reaction, THF was removed in vacuo and the aqueous layer was cooled to 0 °C and acidified with dilute HCl. Then the aqueous layer was extracted with DCM (2 x 30 mL). The organic layer was then dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo to give crude 8-(p- tolylsulfonyloxy)octanoic acid (carboxylic acid-11-C) (330 mg, 1.049 mmol, 87.67% yield) as a colorless sticky gum. LCMS-ESI (pos.) m/z: 315.1 (M+H) ⁺ . [0220] Step-3: Synthesis of benzyl 8-(p-tolylsulfonyloxy)octanoate (carboxylic acid- 11-D): To a stirred solution of 8-(p-tolylsulfonyloxy)octanoic acid (carboxylic acid-11-C) (330 mg, 1.05 mmol) and K ₂ CO ₃ (289 mg, 2.1 mmol) in acetone (10 mL), benzyl bromide (359.03 mg, 2.1 mmol) was added and the reaction mixture was stirred at RT for 16 h. The solvent was evaporated in vacuo and the residue was re-dissolved in EtOAc (15 mL). The organic layer was washed with brine, dried over anhydrous Na ₂ SO _4, and evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 30% EtOAc in hexanes to give benzyl 8-(p-tolylsulfonyloxy)octanoate (carboxylic acid-11-D) (300 mg, 0.742 mmol, 70.66% yield) as a colorless sticky gum. LCMS-ESI (pos.) m/z: 405.3 (M+H) ⁺ . [0221] Step-4: Synthesis of benzyl 8-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin- 4-yl]oxyoctanoate (carboxylic acid-11-E): To a stirred solution of benzyl 8-(p- tolylsulfonyloxy)octanoate (carboxylic acid-11-D) (300 mg, 0.740 mmol) and 2-(2,6-dioxo-3- piperidyl)-4-hydroxy-isoindoline-1,3-dione (264.39 mg, 0.960 mmol) in DMA (5 mL), NaHCO ₃ (124.61 mg, 1.48 mmol) and KI (24.62 mg, 0.150 mmol) were added and the reaction mixture was heated at 95 °C for 4 h. Then the reaction mixture was cooled to RT and poured into ice-cold water and extracted with EtOAc (2 x 15 mL). The combined organic layers were dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 60% EtOAc in hexanes to give benzyl 8-[2-(2,6-dioxo-3- piperidyl)-1,3-dioxo-isoindolin-4-yl]oxyoctanoate (carboxylic acid-11-E) (210 mg, 0.415 mmol, 55.90% yield) as an white solid. LCMS-ESI (pos.) m/z: 507.0 (M+H) ⁺ . [0222] Step-5: Synthesis of 8-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-4- yl]oxyoctanoic acid (carboxylic acid-11): To a stirred solution of benzyl 8-[2-(2,6-dioxo-3- piperidyl)-1,3-dioxo-isoindolin-4-yl]oxyoctanoate (carboxylic acid-11-E) (210 mg, 0.410 mmol) in EtOAc (10 mL) was added and 10% Pd-C (5 mg, 0.050 mmol). Then the reaction mixture was stirred under hydrogen atmosphere using a balloon for 4 h at RT. After completion of the reaction, the reaction mixture was filtered through a celite bed and the bed was washed with EtOAc. The filtrate was then evaporated in vacuo and the crude was triturated with n-pentane to give 8-[2-(2,6- dioxo-3-piperidyl)-1,3-dioxo-isoindolin-4-yl]oxyoctanoic acid (carboxylic acid-11) (105 mg, 0.252 mmol, 60.82% yield) as an white solid. LCMS-ESI (pos.) m/z: 417.2 (M+H) ⁺ . EXAMPLE 33 Preparation of Compounds According to Procedure B: [0223] Additional compounds were prepared according to Procedure B starting from amine-1, amine-2, or amine-3 and a variety of carboxylic acids. Carboxylic acids used in synthesizing compounds 101, 103, 107, 110, 115, 117, and 146 were prepared according to methods described in International Patent Publicatin No. 2022/098843, which is incorporated by reference herein in its entirety. The preparation of compounds via coupling of amines and carboxylic acids is summarized in Table 2 below.

Table 2: Compounds prepared via amine and carboxylic acid coupling according to Procedure B EXAMPLE 34 Synthesis of (2S,4R)-N-[[2-[2-[2-[2-[2-[2-[4-[4-[[6-(6-aminopyrazin-2-yl) imidazo[1,2-a]pyrazin- 8-yl]amino]phenyl]piperazin-1-yl]-2-oxo-ethoxy]ethoxy]ethoxy ]ethoxy]ethoxy]-4-(4- methylthiazol-5-yl)phenyl]methyl]-4-hydroxy-1-[(2S)-3-methyl -2-(1-oxoisoindolin-2- yl)butanoyl]pyrrolidine-2-carboxamide (220) [0224] (2S,4R)-N-[[2-[2-[2-[2-[2-[2-[4-[4-[[6-(6-aminopyrazin-2-yl) imidazo[1,2- a]pyrazin-8-yl]amino]phenyl]piperazin-1-yl]-2-oxo-ethoxy]eth oxy]ethoxy]ethoxy]ethoxy]-4-(4- methylthiazol-5-yl)phenyl]methyl]-4-hydroxy-1-[(2S)-3-methyl -2-(1-oxoisoindolin-2- yl)butanoyl]pyrrolidine-2-carboxamide (220) may be prepared via the reaction of amine-1 and carboxylic acid-1 according to Procedure C shown in Scheme C below. Scheme C [0225] To a stirred solution of 2-[2-[2-[2-[2-[5-(4-methylthiazol-5-yl)-2-[[[(2S,4R)-4- hydroxy-1-[(2S)-3-methyl-2-(1-oxoisoindolin-2-yl)butanoyl]py rrolidine-2- carbonyl]amino]methyl]phenoxy]ethoxy]ethoxy]ethoxy]ethoxy]ac etic acid (carboxylic acid-12) (30 mg, 0.040 mmol) in DMF (1 mL) at 0 °C, HATU (17.48 mg, 0.050 mmol) was added and the reaction mixture was stirred for 15 min at 0 °C. Then 6-(6-aminopyrazin-2-yl)-N-(4-piperazin-1- ylphenyl)imidazo[1,2-a]pyrazin-8-amine dihydrochloride (amine-1) (21.17 mg, 0.050 mmol) and DIPEA (0.03 mL, 0.150 mmol) was added to the reaction mixture and the stirring was continued for overnight at RT. After completion of reaction as monitored by LCMS, the reaction mixture was poured into ice-cold water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous Na ₂ SO ₄ and concentrated in vacuo. The crude was purified by prep-HPLC to give (2S,4R)-N-[[2-[2-[2-[2-[2-[2-[4-[4-[[6-(6-aminopyrazin-2- yl)imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]piperazin-1-yl]-2 -oxo- ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]-4-(4-methylthiazol-5-yl) phenyl]methyl]-4-hydroxy-1- [(2S)-3-methyl-2-(1-oxoisoindolin-2-yl)butanoyl]pyrrolidine- 2-carboxamide (EXAMPLE 220) (6 mg, 0.005 mmol, 13.5% yield) as an white solid. ¹ H NMR (400 MHz, 100 °C, DMSO-d6) δ 9.01 (s, 1H), 8.90 (s, 1H), 8.60 (s, 1H), 8.53 (s, 1H), 8.06 (s, 1H), 7.93 (d, J = 7.9 Hz, 4H), 7.71 (d, J = 7.5 Hz, 1H), 7.63 – 7.56 (m, 3H), 7.53 – 7.43 (m, 1H), 7.35 (d, J = 7.9 Hz, 1H), 7.08 – 6.97 (m, 4H), 6.11 (s, 2H), 4.76 (d, J = 11.3 Hz, 2H), 4.57 (d, J = 18.0 Hz, 1H), 4.53 – 4.44 (m, 2H), 4.43 – 4.28 (m, 3H), 4.20 (d, J = 5.7 Hz, 4H), 3.87 – 3.74 (m, 3H), 3.73 – 3.48 (m, 17H), 3.16 (t, J = 5.2 Hz, 4H), 2.47 (s, 3H), 2.43 – 2.33 (m, 1H), 2.03 (d, J = 7.1 Hz, 2H), 0.98 (d, J = 6.4 Hz, 3H), 0.79 (d, J = 6.5 Hz, 3H). LCMS-ESI (pos.) m/z: 1152.6 (M+H) ⁺ . EXAMPLE 35 Preparation of Compounds According to Procedure C: [0226] Additional compounds were prepared according to Procedure C via amine and carboxylic acid amide formation. Their preparation is summarized in Table 3 below. Table3: Compounds prepared according to Procedure C

EXAMPLE 36 Synthetic scheme for carboxylic acid-12: [0227] Step-1: Synthesis of tert-butyl 2-[2-[2-[2-[2-(p- tolylsulfonyloxy)ethoxy]ethoxy]ethoxy]ethoxy]acetate (carboxylic acid-12-B): To a stirred solution of tert-butyl 2-[2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethoxy]acetate [169751-72-8] (400 mg, 1.3 mmol) and Et3N (0.55 mL, 3.89 mmol) and in DCM (5 mL) at 0 °C was added p- toluenesulfonyl chloride (494.6 mg, 2.59 mmol). The reaction was allowed to warm to RT and stirred at RT for 16 h. The reaction was concentrated to dryness and the residue was taken up in EtOAc (100 mL) and the organic layer was washed with water (2 x 50 mL) and sat. brine solution (1 x 50 mL). The organic layer was then separated and dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 50% EtOAc in hexanes to give tert-butyl 2-[2-[2-[2-[2-(p- tolylsulfonyloxy)ethoxy]ethoxy]ethoxy]ethoxy]acetate (carboxylic acid-12-B) (450 mg, 0.973 mmol, 75% yield). LCMS-ESI (pos.) m/z: 480.4 (M+NH4) ⁺ . [0228] Step-2: Synthesis of tert-butyl 2-[2-[2-[2-[2-[5-(4-methylthiazol-5-yl)-2- [[[(2S,4R)-4-hydroxy-1-[rac-(2S)-3-methyl-2-(1-oxoisoindolin -2-yl)butanoyl]pyrrolidine-2- carbonyl]amino]methyl]phenoxy]ethoxy]ethoxy]ethoxy]ethoxy]ac etate (carboxylic acid-12-C): To a stirred solution of (2S,4R)-4-hydroxy-N-[[2-hydroxy-4-(4-methylthiazol-5- yl)phenyl]methyl]-1-[(2S)-3-methyl-2-(1-oxoisoindolin-2-yl)b utanoyl]pyrrolidine-2- carboxamide (prepared using methods described in International Patent Publication No. WO 2018/119441, which is incorporated herein in its entirety) (450 mg, 0.820 mmol) and tert-butyl 2- [2-[2-[2-[2-(p-tolylsulfonyloxy)ethoxy]ethoxy]ethoxy]ethoxy] acetate (carboxylic acid-12-B) (455.26 mg, 0.980 mmol) in DMF (5 mL) was added Cs2CO3 (534.47 mg, 1.64 mmol) and stirred at 90 °C for 3 h. The reaction was evaporated in vacuo and the residue was taken up in EtOAc (50 mL) and the organic layer was washed with water (2 x 30 mL) and sat. brine solution (1 x 30 mL). The organic layer was separated and dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 5%MeOH in DCM to give tert-butyl 2-[2-[2-[2-[2-[5-(4-methylthiazol-5-yl)-2-[[[(2S,4R)-4- hydroxy-1-[rac-(2S)-3-methyl-2-(1-oxoisoindolin-2-yl)butanoy l]pyrrolidine-2- carbonyl]amino]methyl]phenoxy]ethoxy]ethoxy]ethoxy]ethoxy]ac etate (carboxylic acid-12-C) (350 mg, 0.417 mmol, 50.86% yield). LCMS-ESI (pos.) m/z: 839.5 (M+H) ⁺ . [0229] Step-3: Synthesis of 2-[2-[2-[2-[2-[5-(4-methylthiazol-5-yl)-2-[[[(2S,4R)-4- hydroxy-1-[(2S)-3-methyl-2-(1-oxoisoindolin-2-yl)butanoyl]py rrolidine-2- carbonyl]amino]methyl]phenoxy]ethoxy]ethoxy]ethoxy]ethoxy]ac etic acid (carboxylic acid-12): To a stirred solution of tert-butyl 2-[2-[2-[2-[2-[5-(4-methylthiazol-5-yl)-2-[[[(2S,4R)-4-hydro xy- 1-[(2S)-3-methyl-2-(1-oxoisoindolin-2-yl)butanoyl]pyrrolidin e-2- carbonyl]amino]methyl]phenoxy]ethoxy]ethoxy]ethoxy]ethoxy]ac etate (carboxylic acid-12-C) (350 mg, 0.420 mmol) in DCM (5 mL) at 0 °C was added TFA (0.27 mL, 3.1 mmol)). The reaction was allowed to warm to RT and stirred at RT for 3 h. The reaction was evaporated in vacuo, and the crude residue was triturated with n-pentane and dried to give 2-[2-[2-[2-[2-[5-(4- methylthiazol-5-yl)-2-[[[(2S,4R)-4-hydroxy-1-[(2S)-3-methyl- 2-(1-oxoisoindolin-2- yl)butanoyl]pyrrolidine-2-carbonyl]amino]methyl]phenoxy]etho xy]ethoxy]ethoxy]ethoxy]acetic acid (carboxylic acid-12) (270 mg, 0.345 mmol, 82.67% yield). LCMS-ESI (pos.) m/z: 783.4 (M+H) ⁺ .

EXAMPLE 37 Synthetic scheme for carboxylic acid-13 [0230] Step-1: Synthesis of 2-[2-(2-tert-butoxy-2-oxo-ethoxy)ethoxy]acetic acid (carboxylic acid-13-B): To a stirred solution of 2-[2-(carboxymethoxy)ethoxy]acetic acid [23243-68-7] (220 mg, 1.23 mmol), tert-butanol (91.54 mg, 1.23 mmol), DMAP (15.09 mg, 0.120 mmol) in DCM (5 mL) was added EDC-HCl (355.12 mg, 1.85 mmol) at 0 °C and stirred for 15 min. Then the reaction mixture was stirred at RT for 18 h. The reaction mixture was evaporated in vacuo and the residue was dissolved in H2O (10 mL) and extracted with ethyl acetate (2 x 20 mL). The combined organic layers were dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel) eluting with 10% MeOH in DCM to give the 2-[2-(2-tert-butoxy-2-oxo-ethoxy)ethoxy]acetic acid (carboxylic acid-13-B) (70 mg, 0.299 mmol, 24.19% yield) as a sticky gum. [0231] Step-2: Synthesis of tert-butyl 2-[2-[2-[[(1S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4- methylthiazol-5-yl)phenyl]methylcarbamoyl]pyrrolidine-1-carb onyl]-2,2-dimethyl- propyl]amino]-2-oxo-ethoxy]ethoxy]acetate (carboxylic acid-13-C): To a stirred solution of 2-[2- (2-tert-butoxy-2-oxo-ethoxy)ethoxy]acetic acid (carboxylic acid-13-B) (300 mg, 1.28 mmol), (2S,4R)-1-[(2S)-2-amino-3,3-dimethyl-butanoyl]-4-hydroxy-N-[ [4-(4-methylthiazol-5- yl)phenyl]methyl]pyrrolidine-2-carboxamide hydrochloride [1448189-80-7] (598.1 mg, 1.28 mmol), DIPEA (0.67 mL, 3.84 mmol) in DMF (5 mL) was added EDC-HCl (366.92 mg, 1.92 mmol) and HOBt (259.34 mg, 1.92 mmol) at 0 °C and stirred for 15 min. Then the reaction mixture was stirred at RT for 20 h. The reaction mixture was poured into ice-cold water and extracted with ethyl acetate (2 x 25 mL). The combined organic layers were dried under anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel) eluting with 5% MeOH in DCM to give tert-butyl 2-[2-[2-[[(1S)-1-[(2S,4R)-4- hydroxy-2-[[4-(4-methylthiazol-5-yl)phenyl]methylcarbamoyl]p yrrolidine-1-carbonyl]-2,2- dimethyl-propyl]amino]-2-oxo-ethoxy]ethoxy]acetate (carboxylic acid-13-C) (380 mg, 0.499 mmol, 38.99% yield) as an off-white sticky solid. LCMS-ESI (pos.) m/z: 647.3 (M+H) ⁺ . [0232] Step-3: Synthesis of 2-[2-[2-[[(1S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4- methylthiazol-5-yl)phenyl]methylcarbamoyl]pyrrolidine-1-carb onyl]-2,2-dimethyl- propyl]amino]-2-oxo-ethoxy]ethoxy]acetic acid (carboxylic acid-13): To a stirred solution of tert- butyl 2-[2-[2-[[(1S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4-methylthiazol-5 - yl)phenyl]methylcarbamoyl]pyrrolidine-1-carbonyl]-2,2-dimeth yl-propyl]amino]-2-oxo- ethoxy]ethoxy]acetate (carboxylic acid-13-C) (370 mg, 0.570 mmol) in DCM (4.99 mL) at 0 °C, TFA (5.99 mL, 77.78 mmol) was added and the resulting mixture was stirred for another 30 min at 0 °C. Then the reaction mixture was stirred at RT for 2 h. After completion of the reaction, solvent and excess TFA was removed under reduced pressure and the crude was purified by Combiflash column chromatography (230-400 mesh silica gel) eluting with 15% MeOH in DCM to give 2-[2-[2-[[(1S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4-methylthiazol-5 - yl)phenyl]methylcarbamoyl]pyrrolidine-1-carbonyl]-2,2-dimeth yl-propyl]amino]-2-oxo- ethoxy]ethoxy]acetic acid (carboxylic acid-13) (150 mg,0.241 mmol, 42.2% yield) as an off-white sticky solid. LCMS-ESI (pos.) m/z: 591.5 (M+H) ⁺ . EXAMPLE 38 Synthetic scheme for carboxylic acid-15: [0233] Synthesis tert-butyl 11-[[(1S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4-methylthiazol-5- yl)phenyl]methylcarbamoyl]pyrrolidine-1-carbonyl]-2,2-dimeth yl-propyl]amino]-11-oxo- undecanoate (carboxylic acid-15-B): To a solution of [(1S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4- methylthiazol-5-yl)phenyl]methylcarbamoyl]pyrrolidine-1-carb onyl]-2,2-dimethyl- propyl]ammonium chloride [1448189-80-7] (100 mg, 0.210 mmol) in DMF (2 mL), 11-tert- butoxy-11-oxo-undecanoic acid [1789702-17-5] (58.32 mg, 0.210 mmol), EDC-HCl (61.35 mg, 0.320 mmol), HOBt (43.36 mg, 0.320 mmol) and DIPEA (0.15 mL, 0.860 mmol) were added at 0 °C and stirred at RT for 16 h. The reaction mixture was extracted with ethyl acetate, washed with NaHCO3 solution, water, and brine solution and then dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 5% MeOH in DCM to give tert-butyl 11-[[(1S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4- methylthiazol-5-yl)phenyl]methylcarbamoyl]pyrrolidine-1-carb onyl]-2,2-dimethyl- propyl]amino]-11-oxo-undecanoate (carboxylic acid-15-B) (110 mg, 0.155 mmol, 72.59% yield) as a sticky liquid. LCMS-ESI (pos.) m/z: 685.4 (M+H) ⁺ . [0234] Step-2: Synthesis 11-[[(1S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4-methylthiazol-5- yl)phenyl]methylcarbamoyl]pyrrolidine-1-carbonyl]-2,2-dimeth yl-propyl]amino]-11-oxo- undecanoic acid (carboxylic acid-15): To a solution of tert-butyl 11-[[(1S)-1-[(2S,4R)-4-hydroxy- 2-[[4-(4-methylthiazol-5-yl)phenyl]methylcarbamoyl]pyrrolidi ne-1-carbonyl]-2,2-dimethyl- propyl]amino]-11-oxo-undecanoate (carboxylic acid-15-B) (100 mg, 0.150 mmol) in DCM (1 mL), TFA (2 mL, 25.96 mmol), was added at 0 °C and stirred at RT for 4 h. The reaction mixture was concentrated in vacuo, and the residue was triturated with pentane and co-evaporated with toluene to give 11-[[(1S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4-methylthiazol-5- yl)phenyl]methylcarbamoyl]pyrrolidine-1-carbonyl]-2,2-dimeth yl-propyl]amino]-11-oxo- undecanoic acid (carboxylic acid-15) (80 mg, 0.118 mmol, 80.60% yield) as a sticky solid. LCMS-ESI (pos.) m/z: 629.6 (M+H) ⁺ . EXAMPLE 39 Synthetic scheme for carboxylic acid-17: [0235] Step-1: Synthesis of tert-butyl 2-[2-(p-tolylsulfonyloxy)ethoxy]acetate (carboxylic acid-17-B): To a stirred solution of tert-butyl 2-(2-hydroxyethoxy)acetate (500 mg, 2.84 mmol) in DCM (5 mL) was added Et ₃ N (1.19 mL, 8.51 mmol) and p-toluenesulfonyl chloride (595.07 mg, 3.12 mmol) respectively. The reaction was allowed to stir at RT for 16 h. The reaction mixture was evaporated in vacuo and the crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 35% EtOAc in hexane to give tert-butyl 2-[2-(p-tolylsulfonyloxy)ethoxy]acetate (carboxylic acid-17-B) (500 mg, 1.513 mmol, 53.33% yield) as a color less syrup. [0236] Step-2: Synthesis of tert-butyl 2-[2-[5-(4-methylthiazol-5-yl)-2-[[[(2S,4R)-4- hydroxy-1-[(2S)-3-methyl-2-(1-oxoisoindolin-2-yl)butanoyl]py rrolidine-2- carbonyl]amino]methyl]phenoxy]ethoxy]acetate (carboxylic acid-17-D): To a stirred solution of (2S,4R)-4-hydroxy-N-[[2-hydroxy-4-(4-methylthiazol-5-yl)phen yl]methyl]-1-[(2S)-3-methyl- 2-(1-oxoisoindolin-2-yl)butanoyl]pyrrolidine-2-carboxamide (prepared using methods described in International Patent Publication No. WO 2018/119441, which is incorporated herein in its entirety) (carboxylic acid-17-C) (436.27 mg, 0.800 mmol) and tert-butyl 2-[2-(p- tolylsulfonyl)ethoxy]acetate (carboxylic acid-17-B) (250 mg, 0.800 mmol) in DMF (5 mL) was added Cs2CO3 (777.24 mg, 2.39 mmol) at RT and the reaction was heated at 90 °C for 4 h. After completion of the reaction, the reaction mixture was filtered through a cartridge and diluted with cold water (5 mL) and was extracted with EtOAc (10 mL). The organic layer was evaporated in vacuo and the resulting crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 5% MeOH in DCM to give tert-butyl 2-[2-[5-(4-methylthiazol-5-yl)-2- [[[(2S,4R)-4-hydroxy-1-[(2S)-3-methyl-2-(1-oxoisoindolin-2-y l)butanoyl]pyrrolidine-2- carbonyl]amino]methyl]phenoxy]ethoxy]acetate (carboxylic acid-17-D) (180 mg, 0.238 mmol, 29.92% yield) as an off-white solid. LCMS-ESI (pos.) m/z: 707.4 (M+H) ⁺ . [0237] Step-3: Synthesis of 2-[2-[5-(4-methylthiazol-5-yl)-2-[[[(2S,4R)-4-hydroxy-1- [(2S)-3-methyl-2-(1-oxoisoindolin-2-yl)butanoyl]pyrrolidine- 2- carbonyl]amino]methyl]phenoxy]ethoxy]acetic acid (carboxylic acid-17): To a stirred solution of tert-butyl 2-[2-[2-[2-[[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin- 5- yl]amino]ethoxy]ethoxy]ethoxy]acetate (carboxylic acid-17-D) (184 mg, 0.261 mmol) in dry DCM (2 mL), TFA (0.27 mL, 3.65 mmol) was added at 0 °C the reaction mixture was stirred at RT for 3 h. After completion of the reaction, the solvent and excess TFA was evaporated in vacuo. The crude mixture was triturated with n-pentane (2 x 3 mL) followed by diethyl ether (2 x 3 mL) and dried in vacuo to give 2-[2-[2-[2-[[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin- 5- yl]amino]ethoxy]ethoxy]ethoxy]acetic acid (carboxylic acid-17) (135 mg, 0.187 mmol, 71.66% yield) as a brown sticky gummy liquid. LCMS-ESI (pos.) m/z: 651.2 (M+H) ⁺ . EXAMPLE 40 Synthetic scheme for carboxylic acid-18: [0238] Step-1: Synthesis of tert-butyl 2-[2-[2-(p- tolylsulfonyloxy)ethoxy]ethoxy]acetate (carboxylic acid-18-B): To a stirred solution of tert-butyl 2-[2-(2-hydroxyethoxy)ethoxy]acetate [149299-82-1] (400 mg, 1.82 mmol) in DCM (25 mL) at 0 °C, p-toluenesulfonyl chloride (692.45 mg, 3.63 mmol) and Et ₃ N (1.02 mL, 7.26 mmol) were added and the reaction mixture was stirred at 0 °C for another 30 min. Then the reaction mixture was stirred overnight at RT. After completion of the reaction, water (20 mL) was added to the reaction mixture and extracted with DCM (30 mL). The organic layer was washed with brine, dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel) eluting with 30% EtOAc in hexanes to give tert-butyl 2-[2-[2-(p-tolylsulfonyloxy)ethoxy]ethoxy]acetate (carboxylic acid-18-B) (500 mg, 1.335 mmol, 73.53% yield) as a colorless sticky gum. [0239] Step-2: Synthesis of tert-butyl 2-(2-(2-(2-(((2S,4R)-4-hydroxy-1-((S)-3- methyl-2-(1-oxoisoindolin-2-yl)butanoyl)pyrrolidine-2-carbox amido)methyl)-5-(4- methylthiazol-5-yl)phenoxy)ethoxy)ethoxy)acetate (carboxylic acid-18-C): To a stirred solution of tert-butyl 2-[2-[2-(p-tolylsulfonyloxy)ethoxy]ethoxy]acetate (carboxylic acid-18-B) (258.74 mg, 0.690 mmol) in DMF (3 mL) were added (2S,4R)-4-hydroxy-N-[[2-hydroxy-4-(4- methylthiazol-5-yl)phenyl]methyl]-1-[(2S)-3-methyl-2-(1-oxoi soindolin-2- yl)butanoyl]pyrrolidine-2-carboxamide (prepared using methods described in International Patent Publication No. WO 2018/119441, which is incorporated herein in its entirety), carboxylic acid- 17-C (300 mg, 0.550 mmol) and Cs ₂ CO ₃ (356.31 mg, 1.09 mmol) at 90 °C and stirred for 3 h. The reaction mixture was filtered over a celite pad and the filtrate was evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 5% MeOH in DCM to give tert-butyl 2-(2-(2-(2-(((2S,4R)-4-hydroxy-1-((S)-3-methyl-2-(1- oxoisoindolin-2-yl)butanoyl)pyrrolidine-2-carboxamido)methyl )-5-(4-methylthiazol-5- yl)phenoxy)ethoxy)ethoxy)acetate (carboxylic acid-18-C) (150 mg, 0.204 mmol, 37.23% yield). LCMS-ESI (pos.) m/z: 751.4 (M+H) ⁺ . [0240] Step-3: Synthesis of tert-butyl 2-(2-(2-(2-(((2S,4R)-4-hydroxy-1-((S)-3- methyl-2-(1-oxoisoindolin-2-yl)butanoyl)pyrrolidine-2-carbox amido)methyl)-5-(4- methylthiazol-5-yl)phenoxy)ethoxy)ethoxy)acetate (carboxylic acid-18): To a stirred solution of tert-butyl 2-(2-(2-(2-(((2S,4R)-4-hydroxy-1-((S)-3-methyl-2-(1-oxoisoin dolin-2- yl)butanoyl)pyrrolidine-2-carboxamido)methyl)-5-(4-methylthi azol-5- yl)phenoxy)ethoxy)ethoxy)acetate (carboxylic acid-18-C) (146.34 mg, 0.200 mmol) in DCM (3 mL) at 0 °C was added TFA (0.03 mL, 0.300 mmol). The reaction was allowed to warm to room temperature and stirred at RT for 4 h. The reaction was evaporated in vacuo, and the residue was triturated with n-pentane and dried in vacuo to give 2-(2-(2-(2-(((2S,4R)-4-hydroxy-1-((S)-3- methyl-2-(1-oxoisoindolin-2-yl)butanoyl)pyrrolidine-2-carbox amido)methyl)-5-(4- methylthiazol-5-yl)phenoxy)ethoxy)ethoxy)acetic acid (carboxylic acid-18) (110.4 mg,0.162 mmol, 80.10% yield). LCMS-ESI (pos.) m/z: 695.5 (M+H) ⁺ . EXAMPLE 41 Synthetic scheme for carboxylic acid-19: [0241] Step-1: Synthesis of tert-butyl 2-[2-[[(1S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4- methylthiazol-5-yl)phenyl]methylcarbamoyl]pyrrolidine-1-carb onyl]-2,2-dimethyl- propyl]amino]-2-oxo-ethoxy]acetate (carboxylic acid-19-B): To a solution of [(1S)-1-[(2S,4R)- 4-hydroxy-2-[[4-(4-methylthiazol-5-yl)phenyl]methylcarbamoyl ]pyrrolidine-1-carbonyl]-2,2- dimethyl-propyl]ammonium chloride [1448189-80-7] (350 mg, 0.750 mmol) in DMF (5 mL), 2- (2-tert-butoxy-2-oxo-ethoxy)acetic acid [120289-22-7] (142.53 mg, 0.750 mmol), EDC-HCl (214.71 mg, 1.12 mmol), HOBt (151.76 mg, 1.12 mmol) and DIPEA (0.52 mL, 3 mmol) were added at 0 °C and stirred at RT for 16 h. The reaction mixture was extracted with ethyl acetate, and the organic layer was washed with NaHCO3 solution, followed by water and brine solution, and then dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 5% MeOH in DCM to give tert-butyl 2-[2-[[(1S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4-methylthiazol-5- yl)phenyl]methylcarbamoyl]pyrrolidine-1-carbonyl]-2,2-dimeth yl-propyl]amino]-2-oxo- ethoxy]acetate (carboxylic acid-19-B) (375 mg, 0.569 mmol, 75.94% yield) as a sticky liquid. LCMS-ESI (pos.) m/z: 603.4 (M+H) ⁺ . [0242] Step-2: Synthesis of 2-[2-[[(1S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4-methylthiazol- 5-yl)phenyl]methylcarbamoyl]pyrrolidine-1-carbonyl]-2,2-dime thyl-propyl]amino]-2-oxo- ethoxy]acetic acid (carboxylic acid-19): To a solution of tert-butyl 2-[2-[[(1S)-1-[(2S,4R)-4- hydroxy-2-[[4-(4-methylthiazol-5-yl)phenyl]methylcarbamoyl]p yrrolidine-1-carbonyl]-2,2- dimethyl-propyl]amino]-2-oxo-ethoxy]acetate (carboxylic acid-19-B) (375 mg, 0.620 mmol) in DCM (4 mL) at 0 °C, TFA (6 mL, 77.89 mmol) was added and stirred at RT for 4 h. The reaction mixture was evaporated in vacuo, and the resulting residue was triturated with n-pentane and then co-evaporated with toluene to give 2-[2-[[(1S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4-methylthiazol-5- yl)phenyl]methylcarbamoyl]pyrrolidine-1-carbonyl]-2,2-dimeth yl-propyl]amino]-2-oxo- ethoxy]acetic acid (carboxylic acid-19) (290 mg, 0.460 mmol, 73.96% yield) as an off-white sticky solid. LCMS-ESI (pos.) m/z: 547.3 (M+H) ⁺ . EXAMPLE 42 Synthetic scheme for carboxylic acid-20: [0243] Step-1: Synthesis of tert-butyl 5-[[(1S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4- methylthiazol-5-yl)phenyl]methylcarbamoyl]pyrrolidine-1-carb onyl]-2,2-dimethyl- propyl]amino]-5-oxo-pentanoate (carboxylic acid-20-A): To a stirred solution of [(1S)-1- [(2S,4R)-4-hydroxy-2-[[4-(4-methylthiazol-5-yl)phenyl]methyl carbamoyl]pyrrolidine-1- carbonyl]-2,2-dimethyl-propyl]ammonium chloride [1448189-80-7] (350 mg, 0.750 mmol), 5- tert-butoxy-5-oxo-pentanoic acid [63128-51-8] (141.06 mg, 0.750 mmol), EDC-HCl (214.71 mg, 1.12 mmol), HOBt (151.76 mg, 1.12 mmol), in DMF (14 mL), was added DIPEA (0.4 mL, 2.25 mmol) slowly at 0 °C and stirred at RT for 16 h. The reaction was evaporated in vacuo and the residue was taken up in EtOAc (50 mL) and the organic layer was washed with water (1 x 30 mL) and sat. brine solution (5 x 30 mL). The organic layer was then dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel) to give tert-butyl 5-[[(1S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4-methylthiazol-5- yl)phenyl]methylcarbamoyl]pyrrolidine-1-carbonyl]-2,2-dimeth yl-propyl]amino]-5-oxo- pentanoate (carboxylic acid-20-A) (345 mg, 0.574 mmol, 76.63% yield). LCMS-ESI (pos.) m/z: 601.4 (M+H) ⁺ . [0244] Step-2: Synthesis of 5-[[(1S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4-methylthiazol-5- yl)phenyl]methylcarbamoyl]pyrrolidine-1-carbonyl]-2,2-dimeth yl-propyl]amino]-5-oxo- pentanoic acid (carboxylic acid-20): To a stirred solution of tert-butyl 5-[[(1S)-1-[(2S,4R)-4- hydroxy-2-[[4-(4-methylthiazol-5-yl)phenyl]methylcarbamoyl]p yrrolidine-1-carbonyl]-2,2- dimethyl-propyl]amino]-5-oxo-pentanoate (carboxylic acid-20-A) (345 mg, 0.570 mmol) in DCM (8 mL), was added TFA (1 mL, 12.98mmol) slowly at 0 °C. The reaction mixture was stirred at RT for 4 h. The reaction mixture was evaporated and the residue triturated with n-pentane to give 5-[[(1S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4-methylthiazol-5- yl)phenyl]methylcarbamoyl]pyrrolidine-1-carbonyl]-2,2-dimeth yl-propyl]amino]-5-oxo- pentanoic acid (carboxylic acid-20) (295 mg, 0.542 mmol, 94.32% yield). LCMS-ESI (pos.) m/z: 545.3 (M+H) ⁺ . EXAMPLE 43 Synthetic scheme for carboxylic acid-21 [0245] Step-1: Synthesis of tert-butyl 14-[[(1S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4- methylthiazol-5-yl)phenyl]methylcarbamoyl]pyrrolidine-1-carb onyl]-2,2-dimethyl- propyl]amino]-14-oxo-tetradecanoate (carboxylic acid-21-B): To a solution of [(1S)-1-[(2S,4R)- 4-hydroxy-2-[[4-(4-methylthiazol-5-yl)phenyl]methylcarbamoyl ]pyrrolidine-1-carbonyl]-2,2- dimethyl-propyl]ammonium chloride [1448189-80-7] (300 mg, 0.640 mmol) in DMF (5 mL), 14- tert-butoxy-14-oxo-tetradecanoic acid [234082-00-9] (202 mg, 0.640 mmol), EDC-HCl (184.71 mg, 0.960 mmol), HOBt (130.08 mg, 0.960 mmol) and DIPEA (0.45 mL, 2.57 mmol) were added at 0 °C and stirred at RT for 16 h. The reaction mixture was diluted with ethyl acetate, washed with NaHCO3 solution, followed by water and brine solution. The organic layer was dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 5% MeOH in DCM to give tert-butyl 14- [[(1S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4-methylthiazol-5-yl)phen yl]methylcarbamoyl]pyrrolidine- 1-carbonyl]-2,2-dimethyl-propyl]amino]-14-oxo-tetradecanoate (carboxylic acid-21-B) (350 mg, 0.471 mmol, 73.27% yield) as a sticky liquid. LCMS-ESI (pos.) m/z: 727.6 (M+H) ⁺ . [0246] Step-2: Synthesis of 14-[[(1S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4-methylthiazol-5- yl)phenyl]methylcarbamoyl]pyrrolidine-1-carbonyl]-2,2-dimeth yl-propyl]amino]-14-oxo- tetradecanoic acid (carboxylic acid-21): To a solution of tert-butyl 14-[[(1S)-1-[(2S,4R)-4- hydroxy-2-[[4-(4-methylthiazol-5-yl)phenyl]methylcarbamoyl]p yrrolidine-1-carbonyl]-2,2- dimethyl-propyl]amino]-14-oxo-tetradecanoate (carboxylic acid-21-B) (340 mg, 0.470 mmol) in DCM (3 mL), TFA (6 mL, 77.89 mmol) was added at 0 °C and stirred at RT for 4 h. The reaction mixture was evaporated in vacuo, and the residue was triturated with n-pentane and then co-evaporated with toluene to give 14-[[(1S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4-methylthiazol-5- yl)phenyl]methylcarbamoyl]pyrrolidine-1-carbonyl]-2,2-dimeth yl-propyl]amino]-14-oxo- tetradecanoic acid (carboxylic acid-21) (240 mg, 0.317 mmol, 67.80% yield) as a sticky solid. LCMS-ESI (pos.) m/z: 671.6 (M+H) ⁺ . EXAMPLE 44 Synthetic scheme for carboxylic acid-22: [0247] Step-1: Synthesis of 2-[2-[2-[2-[[(1S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4- methylthiazol-5-yl)phenyl]methylcarbamoyl]pyrrolidine-1-carb onyl]-2,2-dimethyl- propyl]amino]-2-oxo-ethoxy]ethoxy]ethoxy]acetic acid (carboxylic acid-22): To a stirred solution of crude 2-[2-[2-(carboxymethoxy)ethoxy]ethoxy]acetic acid [13887-98-4] (350 mg, 1.58 mmol), [(1S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4-methylthiazol-5- yl)phenyl]methylcarbamoyl]pyrrolidine-1-carbonyl]-2,2-dimeth yl-propyl]ammonium chloride [1448189-80-7] (220.7 mg, 0.470 mmol), in DMF (8 mL) were added DIPEA (0.22 mL, 1.26 mmol) and HATU (209.63 mg, 0.550 mmol) at 0 °C and stirred for 15 min. Then the reaction mixture was stirred at RT for 20 h. The reaction mixture was poured into ice-cold water and then extracted with ethyl acetate (2 x 25 mL). The combined organic layers were dried over anhydrous Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by Combiflash chromatography (230- 400 mesh silica gel) eluting with 20% MeOH in DCM to give the 2-[2-[2-[2-[[(1S)-1-[(2S,4R)-4- hydroxy-2-[[4-(4-methylthiazol-5-yl)phenyl]methylcarbamoyl]p yrrolidine-1-carbonyl]-2,2- dimethyl-propyl]amino]-2-oxo-ethoxy]ethoxy]ethoxy]acetic acid (carboxylic acid-22) (85 mg, 0.134 mmol, 8.50% yield) as an off-white sticky solid. LCMS-ESI (pos.) m/z: 635.4 (M+H) ⁺ .

EXAMPLE 45 Synthetic scheme for carboxylic acid-14: [0248] Step-1: Synthesis of tert-butyl 2-[2-[2-[2-(p- tolylsulfonyloxy)ethoxy]ethoxy]ethoxy]acetate (carboxylic acid-14-B): To a stirred solution of tert-butyl 2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]acetate [518044-31-0] (200 mg, 0.760 mmol) and Et3N (0.32 mL, 2.27 mmol) in DCM (3 mL) at 0 °C, was added p-toluenesulfonyl chloride (288.51 mg, 1.51 mmol). The reaction was allowed to warm to RT and stirred at RT for 16 h. The reaction was concentrated to dryness and the residue was taken up in EtOAc (100 mL). The organic layer was washed with water (2 x 50 mL) and sat. brine solution (1 x 50 mL). The organic layer was then separated and dried over anhyd Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 30% EtOAc in hexanes to give tert-butyl 2-[2-[2-[2-(p-tolylsulfonyloxy)ethoxy]ethoxy]ethoxy]acetate (carboxylic acid-14-B) (250 mg, 0.597 mmol, 79% yield). LCMS-ESI (pos.) m/z: 437.2 (M+NH4) ⁺ . [0249] Step-2: Synthesis of tert-butyl 2-[2-[2-[2-[5-(4-methylthiazol-5-yl)-2- [[[(2S,4R)-4-hydroxy-1-[(2R)-3-methyl-2-(1-oxoisoindolin-2-y l)butanoyl]pyrrolidine-2- carbonyl]amino]methyl]phenoxy]ethoxy]ethoxy]ethoxy]acetate (carboxylic acid-14-C): A stirred solution of (2S,4R)-4-hydroxy-N-[[2-hydroxy-4-(4-methylthiazol-5-yl)phen yl]methyl]-1- [(2S)-3-methyl-2-(1-oxoisoindolin-2-yl)butanoyl]pyrrolidine- 2-carboxamide ([1448189-80-7] (300 mg, 0.550 mmol) tert-butyl 2-[2-[2-[2-(p-tolylsulfonyloxy)ethoxy]ethoxy]ethoxy]acetate (carboxylic acid-14-B) (274.6 mg, 0.660 mmol) and Cs2CO3 (356.31 mg, 1.09 mmol) in DMF (2 mL) was heated at 90 °C for 3 h. The reaction was evaporated in vacuo and the residue was taken up in EtOAc (50 mL). The organic layer was washed with water (2 x 30 mL) and sat. brine solution (1 x 30 mL). The organic layer was separated and dried over anhyd Na ₂ SO ₄ and evaporated in vacuo. The crude was purified by Combiflash column chromatography (230-400 mesh silica gel), eluting with 5% MeOH in DCM to yield tert-butyl 2-[2-[2-[2-[5-(4-methylthiazol-5-yl)-2- [[[(2S,4R)-4-hydroxy-1-[(2S)-3-methyl-2-(1-oxoisoindolin-2-y l)butanoyl]pyrrolidine-2- carbonyl]amino]methyl]phenoxy]ethoxy]ethoxy]ethoxy]acetate (carboxylic acid-14-C) (120 mg, 0.151 mmol, 28% yield). LCMS-ESI (pos.) m/z: 795.6 (M+H) ⁺ . [0250] Step-3: Synthesis 2-[2-[2-[2-[5-(4-methylthiazol-5-yl)-2-[[[(2S,4R)-4- hydroxy-1-[(2R)-3-methyl-2-(1-oxoisoindolin-2-yl)butanoyl]py rrolidine-2- carbonyl]amino]methyl]phenoxy]ethoxy]ethoxy]ethoxy]acetic acid (carboxylic acid-14): To a stirred solution of tert-butyl 2-[2-[2-[2-[2-[[[(2S,4R)-4-hydroxy-1-[(2S)-3-methyl-2-(1- oxoisoindolin-2-yl)butanoyl]pyrrolidine-2-carbonyl]amino]met hyl]-5-(4-methylthiazol-5- yl)phenoxy]ethoxy]ethoxy]ethoxy]acetate (carboxylic acid-14-C) (200 mg, 0.250 mmol) in DCM (0.5 mL) at 0 °C was added TFA (0.06 mL, 0.75 mmol) The reaction was allowed to warm to RT and continuously stirred at RT over 3 h. The reaction mixture was evaporated in vacuo, and the residue was triturated with n-pentane and dried to give 2-[2-[2-[2-[2-[[[(2S,4R)-4- hydroxy-1-[(2S)-3-methyl-2-(1-oxoisoindolin-2-yl)butanoyl]py rrolidine-2- carbonyl]amino]methyl]-5-(4-methylthiazol-5-yl)phenoxy]ethox y]ethoxy]ethoxy]acetic acid (carboxylic acid-14) (100 mg, 0.135 mmol, 54% yield). LCMS-ESI (pos.) m/z: 739.4 (M+H) ⁺ . Determination of SYK Degradation [0251] Exemplary compounds were tested for degradation of SYK using a homogenous time resolved fluorescence (HTRF) assay. The HTRF assay was carried out using HTRF TOTAL-SYK DETECTION KITS (PerkinElmer – Part # 64SYKTPEG) using the standard assay protocol provided by PerkinElmer. Two cell lines (OCIAML3 and SUDHL4) were used to test the effect of compounds. Protein degradation (total SYK protein level) measurements were performed with six replicates. The %D _max (the maximum degradation under assay conditions) and DC50 (dose at 50% of the maximum degradation) values were normalized to DMSO and fitted with GraphPad - Prism 9. [0252] Under the assay conditions, the DC ₅₀ ranged from >100 nM to >10 uM. The D _max values observed over the assay concentration range (0.3 nM – 10 uM) for representative compounds are provided below in Table 4. HTRF Dmax Data for Representative Compounds Table 4: SYK degradation for Selected Compounds Determined by HTRF Assay [0253] Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, it is readily apparent to those of ordinary skill in the art in light of the teachings of this invention that certain changes and modifications may be made thereto without departing from the spirit or scope of the appended claims. [0254] Accordingly, the preceding merely illustrates the principles of the invention. It will be appreciated that those skilled in the art will be able to devise various arrangements which, although not explicitly described or shown herein, embody the principles of the invention and are included within its spirit and scope. Furthermore, all examples and conditional language recited herein are principally intended to aid the reader in understanding the principles of the invention and the concepts contributed by the inventors to furthering the art and are to be construed as being without limitation to such specifically recited examples and conditions. Moreover, all statements herein reciting principles, aspects, and embodiments of the invention as well as specific examples thereof, are intended to encompass both structural and functional equivalents thereof. Additionally, it is intended that such equivalents include both currently known equivalents and equivalents developed in the future, i.e., any elements developed that perform the same function, regardless of structure. Moreover, nothing disclosed herein is intended to be dedicated to the public regardless of whether such disclosure is explicitly recited in the claims.