TREX1 INHIBITORS AND USES THEREOF CROSS-REFERENCE [0001] This application claims the benefit of U. S. Provisional Application Serial No.63/354,610 filed June 22, 2022 and U. S. Provisional Application Serial No.63/390,199 filed July 18, 2022; which are hereby incorporated by reference in their entirety. BACKGROUND OF THE INVENTION [0002] The presence of tumor infiltrating T cells (“TILs”) is associated with improved clinical outcomes in multiple tumor types and also improves responses to immune checkpoint blockade therapies. Although T-cell responses to some tumors occur spontaneously, the majority of cancers are not naturally recognized by the immune system or have evolved multiple mechanisms of immune evasion. Preclinical and clinical data together have established a central role for type I interferons (“IFNs”) in linking innate and adaptive immune responses to mediate tumor rejection. Non-T cell-inflamed tumors in humans are deficient in type I IFNs. Thus, the development of therapeutic strategies for restoring type I IFN signaling is essential for expanding the number of patients who may be effectively treated with immunotherapy. [0003] Innate immune sensing in the tumor microenvironment (“TME”) is a critical step in promoting spontaneous tumor-initiated T cell priming and subsequent TIL infiltration (Fuertes et al., J. Exp. Med. 2011, 208, 2005-2016). Transcriptional profiling analyses of melanoma patients has revealed that tumors containing infiltrating activated T cells are characterized by a type I IFN transcriptional signature (Harlin et al., Cancer Res.2009, 69, 3077-3085). Studies in mice have demonstrated that type I IFN signaling plays a critical role in tumor-initiated T cell priming (Diamond et al., J. Exp. Med.2011, 208, 1989-2003; and Fuertes et al., J. Exp. Med.2011, 208, 2005-2016). Mice lacking the IFN-α/β receptor in dendritic cells (“DCs”) cannot reject immunogenic tumors and CD8α ⁺ DCs from these mice are defective in antigen cross-presentation to CD8 ⁺ T cells. Furthermore, Baft3 ^-/- mice that lack the CD8α ⁺ DC lineage lose the capacity to spontaneously prime tumor-specific CD8 ⁺ T cells (Fuertes et al., J. Exp. Med.2011, 208, 2005-2016; and Hildner et al., Science 2008, 322, 1097-1100). These findings in humans and in mice indicate that the tumor-resident antigen presenting cell (“APC”) compartment is deficient/absent in non T cell-inflamed tumors. Thus, strategies to induce type I IFN signaling and APC activation in the TME to bridge the innate and adaptive immune responses may have therapeutic utility. [0004] How the innate immune system is engaged by targeted ligands shapes the development of an adaptive response and is central to effective immunotherapy (Dubensky et al., Ther. Adv. Vaccines 2013, 1, 131-143; and Dubensky and Reed, Semin. Immunol.2010, 22, 155-161). The design and development of ligands to activate innate immunity is guided by a fundamental understanding that conserved microbial structures known as Pathogen-Associated Molecular Patterns (“PAMPs”) are sensed by germ-line encoded host cell Pattern Recognition Receptors (“PRRs”), triggering a downstream signaling cascade resulting in the induction of cytokines and chemokines, and initiation of a specific adaptive immune response (Iwasaki and Medzhitov, Science 2010, 327, 291-295). Engagement of the innate immune system by PAMPs presented from an infectious agent or by cellular danger signals known as Danger Associated Molecular Patterns (“DAMPs”) shapes the development of the adaptive antigen-specific response. One objective in the design of innate immune activators is to select defined PAMPs, DAMPS, or synthetic molecules which activate designated PRRs and initiate a desired response. Innate immune ligands (agonists) such as monophosphoryl lipid A (“MPL”) and CpG are microbial-derived PAMPs recognized by Toll-like receptors (“TLRs”), a class of PRRs that signal through MyD88 and TRIF adaptor molecules and mediate induction of NF-kB dependent proinflammatory cytokines (Kawai and Akira, Nat. Immunol.2010, 11, 373-384). While TLRs present on the cell surface (e.g., TLR-4) and endosomes (e.g., TLR-9) sense extracellular and vacuolar pathogens, the productive growth cycle of multiple pathogens including viruses and intracellular bacteria occurs in the cytosol. The compartmentalization of extracellular, vacuolar, and cytosolic PRRs has led to the hypothesis that the innate immune system can sense particular productively replicating pathogenic microbes by monitoring the cytosol (Vance et al., Science 2009, 323, 1208-1211). This provides a rationale for the use of agonists that activate PRRs comprising the cytosolic surveillance pathway and may be an effective strategy for the design of innate immune activators for cancer immunotherapy. [0005] Nucleic acids from bacterial, viral, protozoan, and fungal pathogens are sensed by several distinct cytosolic signaling pathways. When activated, these individual pathways induce a characteristic cytokine profile, which in turn shapes the antigen (“Ag”)-specific immune response. For example, the nucleotide binding oligomerization domain (“NOD”)-like receptor (“NLR”) family, such as “absent in melanoma 2” (“AIM2”), senses cytosolic double-stranded (“ds”) DNA, triggering activation of the inflammasome and caspase-1 dependent production of IL-1β (Strowig et al., Nature 2012, 481, 278-286). The signaling cascade resulting from activation of the inflammasome stimulates priming of Th17-biased CD4 ⁺ T cell immunity, associated with protection against diverse pathogens, such as Streptococcus pneumoniae (Olliver et al., Infect. Immun.2011, 79, 4210-4217). [0006] Type I interferons (IFN-α, IFN-β) are the signature cytokines induced by two distinct TLR- independent cytosolic signaling pathways. In the first pathway, various forms of single-stranded and double-stranded (“ds”) RNA are sensed by RNA helicases, including retinoic acid-inducible gene I (“RIG-I”) and melanoma differentiation-associated gene 5 (“MDA-5”), and through the IFN-β promoter stimulator 1 (“IPS-1”) adaptor protein mediate phosphorylation of the IRF-3 transcription factor, leading to induction of IFN-β (Ireton and Gale, Viruses 2011, 3, 906-919). IPS-1 ^-/- deficient mice have increased susceptibility to infection with RNA viruses. Sensors that signal through the IPS-1 pathway are directly targeted for inactivation by various viral proteins, demonstrating a requirement of this cytosolic host defense pathway to control productive virus infection. Synthetic dsRNA, such as polyinosinic:polycytidylic acid (“poly (I:C)”) and poly ICLC, an analog that is formulated with poly L lysine to resist RNase digestion, is an agonist for both TLR3 and MDA5 pathways, is a powerful inducer of IFN-β, and is currently being evaluated in several diverse clinical settings (Caskey et al., J. Exp. Med. 2011, 208, 2357-2366). [0007] Stimulator of Interferon Genes (“STING”) is the central mediator for the second cytosolic pathway that triggers type I interferon in response to sensing cytosolic double-stranded (“ds”) DNA from infectious pathogens or aberrant host cells (DAMPS) (Motwani, Nat. Rev. Genet.2019, 20, 657-674, and Barber, Curr. Opin. Immunol.2011, 23, 10-20). Alternatively known as TMEM173, MITA, ERIS, and MPYS, STING was discovered by Glen Barber and colleagues using cDNA expression cloning methods as a MyD88-independent host cell defense factor expressed in macrophages, dendritic cells, and fibroblasts, and was found to induce expression of IFN-β and NF-κB dependent pro-inflammatory cytokines in response to sensing cytoplasmic DNA (Ishikawa and Barber, Nature 2008, 455, 674-678). Significantly, and of particular relevance to the therapeutic modulation of STING, activation of this pathway occurs in response to sensing host cell DNA in the cytoplasm, originating from the nucleus or the mitochondria, both in a paracrine and autocrine fashion (Chen et al., Nat. Immunol.2016, 17, 1142- 1149). [0008] Recent work has demonstrated that activation of the STING pathway in tumor-resident host APCs is required for induction of a spontaneous CD8 ⁺ T cell response against tumor-derived antigens in vivo (Woo et al., Immunity 2014, 41, 830-842; and Corrales et al., J. Clin. Invest.2016, 126, 404-411). In addition, activation of this pathway and the subsequent production of IFN-β contributes to the anti-tumor effect of radiation, which can be potentiated with co-administration of a natural STING agonist (Deng et al., Immunity 2014, 41, 843-852). STING is a transmembrane protein localized to the endoplasmic reticulum that undergoes a conformational change in response to direct binding of cyclic dinucleotides (“CDNs”), resulting in a downstream signaling cascade involving TBK1 activation, IRF-3 phosphorylation, and production of IFN-β and other cytokines (Burdette et al., Nature 2011, 478, 515- 518; Burdette and Vance, Nat. Immunol.2013, 14, 19-26; and Ishikawa and Barber, Nature 2008, 455, 674-678). After CDN binding by STING, canonical NF-κB dependent cytokines are also induced (Chen et al., Nat. Immunol.2016, 17, 1142-1149). IFN-β is the signature cytokine induced in response to STING activation, by either exogenous CDNs produced by bacterial infection, or through binding of a structurally distinct endogenous CDN produced by a host cyclic GMP-AMP synthetase (“cGAS”) in response to sensing cytosolic double-stranded DNA (“dsDNA”) (Ablasser et al., Nature 2013, 498, 380- 384; Diner et al., Cell Rep.2013, 3, 1355-1361; McWhirter et al., J. Exp. Med.2009, 206, 1899-1911; Sun et al., Science 2013, 339, 786-791; Woodward et al., Science 2010, 328, 1703-1705; and Zhang et al., Mol. Cell 2013, 51, 226-235). IFNs stimulate expression of interferon-stimulated genes (“ISGs”), a key event that links host innate immunity to the initiation of adaptive immunity. These observations suggested that direct activation of the STING pathway in the TME with specific agonists might be an effective therapeutic strategy to promote broad tumor-initiated T cell priming against an individual’s unique tumor antigen repertoire. [0009] STING is expressed ubiquitously in both immune and somatic cells. Initial clinical approaches to target STING have primarily utilized intratumoral (“IT”) administration of synthetic modified CDNs, to avoid possible toxicity including a cytokine storm or cytokine release syndrome due to expression of high levels of pro-inflammatory cytokines such as IL-6 and TNF-α resulting from broad activation of STING with the systemic administration of potent ligands/agonists. As a single agent, IT injection of CDNs demonstrates potent anti-tumor effects in multiple syngeneic mouse tumor models without significant local or systemic toxicity. Direct IT injection of selected CDNs in established B16 melanoma, CT26 colon, and 4T1 breast carcinomas resulted in rapid and profound tumor regression and promoted lasting systemic antigen-specific T cell immunity (Sivick et al., Cell Rep.2018, 25, 3074-3085; Corrales et al., Cell Rep.2015, 11, 1018-1030; Foote et al., Cancer Immunol. Res.2017, 5, 468-479; and Francica et al., Cancer Immunol. Res.2018, 6, 422-433). In particular, these preclinical investigations demonstrated that tumor-specific CD8 ⁺ T cells primed locally in the draining lymph node serving the injected tumor could traffic to and cause the regression of distal non-injected tumors, supporting the scientific rationale for evaluation of STING agonists to treat patients with advanced metastatic cancers. [0010] Distinct metastatic tumors are genetically diverse and have unique antigenic repertoires. In order to grow, proliferate, and spread, tumors evolve to avoid immune recognition via a process known as immunoediting. Silencing or deletion of genes encoding proteins required for antigen presentation can prevent presentation of particular antigens of major histocompatibility complex (“MHC”) class I and class II molecules, hindering recognition by antigen-specific cytolytic T cells and preventing tumor cell death (Mittal et al., Curr. Opin. Immunol.2014, 27, 16-25). The immunoediting process is constant due to the genetic instability of tumor cells, such that the antigens presented by a given metastatic tumor in an individual with advanced cancer can be distinct from those presented by a distinct metastatic tumor ^{lesion. The genetic heterogeneity in evolving progressing tumors means that a CD8+ T cell with} specificity for a designated antigen expressed on one tumor cell, with said CD8 ⁺ T cell able to kill that tumor cell, may not recognize a separate and distinct tumor because its cognate antigen is not presented on that tumor cell. Implanted mouse tumor models, in comparison, lack genetic heterogeneity because these models are based on homogenous tumor cell lines that grow to lethality before immune selection. Thus, tumor-specific CD8 ⁺ T cells primed locally in the draining lymph node serving an injected tumor can traffic to and eradicate distal non-injected tumors. This observation in mice, which has been referred to as an abscopal effect, is an artificial model of human cancer because the identical tumor cell line, e.g., CT26 colorectal tumor cells, is implanted on opposite flanks of the mouse. [0011] There is a need for broad priming of tumor antigen-specific CD4 ⁺ and CD8 ⁺ T cells in the lymph nodes that serve diverse metastatic tumors that are spread throughout the body of an affected individual with advanced cancer. Efficient systemic delivery of ligands to activate designated innate immune receptors selectively in the tumor microenvironment, but not broadly in extra-tumoral tissues where targeted immune receptors are expressed, is a desired therapeutic outcome. Such selective targeting of designated innate immune receptors in the TME is anticipated to induce desired IRF3- and NF-κB-dependent pro-inflammatory cytokines and chemokines that are required to recruit, activate, and initiate innate and adaptive immune cell populations, resulting in priming of tumor-specific T cell immunity. On the other hand, broad non-selective activation of innate immune receptors upon systemic delivery is not desired as high systemic levels of IRF3- and NF-κB-dependent pro-inflammatory cytokines and chemokines such as IFN-β, TNF-α, IFN-γ, IL-12p70, and IL-6 limits tolerability, can result in toxicity, and limits the effectiveness of priming tumor-specific immunity resulting from innate immune activation selectively in the TME. STING has been shown in mice to be a critical innate immune receptor for development of antigen-specific T cell immunity, and genetic mutations in STING result in a significant inflammatory disease in humans known as STING-associated vasculopathy with onset in infancy (“SAVI”), providing scientific rationale for targeting the STING pathway to initiate tumor- specific immunity (Fuertes et al., J. Exp. Med.2011, 208, 2005-2016). However, because STING is expressed broadly in diverse immune cell and somatic cell populations, an efficient means to target activation of the STING pathway selectively in the TME with a systemically delivered (e.g., orally, or intravenously) agent is highly desirable as a therapeutic approach to initiate tumor-antigen specific priming against diverse metastases and effective tumor eradication. While STING is ubiquitously expressed in both immune and somatic cell populations, three prime repair exonuclease 1 (“TREX1”) is a 3’-5’ DNA exonuclease that maintains immune homeostasis by limiting activation of cGAS-STING in normal cells. TREX1 is induced by cytosolic DNA resulting from inflammation, DNA repair deficiency, chemotherapy, or radiotherapy. Severe human inflammatory diseases including Aicardi-Goutières syndrome (“AGS”) and chilblain lupus are interferonopathies resulting from inactivating genetic mutations in TREX1, lead to increased levels of cytosolic dsDNA and chronic activation of the STING pathway. TREX1 is an upstream regulatory mediator of radiation- induced anti-tumor immunity, and the immunity induced by radiation is STING-dependent (Deng et al., Immunity 2014, 41, 843-852). Radiation dose is reversibly correlated with the induced level of IFN-β, the signature cytokine of activated STING. At high radiation dose levels, TREX1 is significantly induced at levels which substantially degrades cytosolic DNA, leading to lower levels of production of cGAMP by cGAS and correspondingly decreased activation of STING and induction of IFN-β. In contrast, hyperfractionated radiation (lower dose levels of radiation delivered over multiple doses) does not affect TREX1 levels and leads to significantly higher levels of IFN-β and development of effective anti-tumor immunity and tumor regression (Vanpouille-Box et al., Nature Comm.2017, 8, 15618-15632). However, effective anti-tumor immunity and tumor regression can be optimally achieved when delivery of high- dose radiotherapy administered as a single dose and/or hypofractionated in conjunction with SBRT—to maximize tumor killing and dsDNA levels—is combined with an effective TREX-1 inhibitor. Genotoxic stress-mediated induction of TREX1 can also be achieved by DNA-modifying chemotherapeutic agents, including dsDNA crosslinking alkylating agents such as nimustine, carmustine, fotemustine, and topotecan (Tomicic et al., Biochimica et Biophysica Acta 2013, 1835, 11-27). Many advanced cancers exhibit deficient DNA repair, due to mutations in genes encoding proteins involved in various DNA repair pathways, leading to genomic plasticity and, consequently, increased tumor virulence. These mutations also result in increased levels of cytosolic DNA and correspondingly increased levels of TREX1, which in turn sufficiently degrades cytosolic DNA and diminishes the extent of activation of the cGAS-STING pathway. Thus, high levels of TREX1 expression facilitate evasion of immune recognition, and therapeutic intervention with agents that both increase the level of TME cytosolic dsDNA and inhibit TREX1 will result in profound activation of the cGAS-STING pathway and development of effective anti-tumor immunity. BRIEF SUMMARY OF THE INVENTION [0012] Disclosed herein is a compound of Formula (I), or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof: Formula (I) as disclosed herein. [0013] Disclosed herein is a compound of Formula (Ia), or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof: Formula (Ia) as disclosed herein. [0014] Disclosed herein is a compound of Formula (Ia-1), or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof: Formula (Ia-1) as disclosed herein. [0015] Disclosed herein is a compound of Formula (Ic), or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof: Formula (Ic) as disclosed herein. [0016] Also disclosed herein is a pharmaceutical composition comprising a compound disclosed herein, or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, and a pharmaceutically acceptable excipient. [0017] Also disclosed herein is a method of treating cancer in a subject in need thereof, the method comprising administering a compound disclosed herein, or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof. In some embodiments, the cancer is characterized a DNA repair deficiency in one or more DNA repair pathways. In some embodiments, the DNA repair deficiency is a deficiency in the base excision repair (“BER”) pathway, the Fanconi anaemia-mediated repair (“FA”) pathway, the homologous recombination (“HR”) pathway, the nucleotide excision repair (“NER”) pathway, the non-homologous end joining (“NHEJ”) pathway, the mismatch repair (“MMR”) pathway, the RecQ-mediated repair (“RecQ”) pathway, or the double-stranded breaks (“DSB”) pathway. In some embodiments, the DNA repair deficiency is a deficiency in the homologous recombination (“HR”) pathway. In some embodiments, the DNA repair deficiency is a BRCA1 mutation. In some embodiments, the method further comprises administering a DNA repair inhibitor. In some embodiments, the DNA repair inhibitor is a poly ADP ribose polymerase (“PARP”) inhibitor. In some embodiments, the method further comprises administering an alkylating agent. In some embodiments, the alkylating agent is cyclophosphamide, chlormethine, uramustine, melphalan, chlorambucil, ifosfamide, bendamustine, carmustine, lomustine, nimustine, fotemustine, streptozocin, or busulfan. In some embodiments, the method further comprises administering a DNA damaging agent. In some embodiments, the DNA damaging agent is camptothecin, etoposide, oxaliplatin, cisplatin, or doxorubicin. In some embodiments, the compound is administered in conjunction with high-dose radiotherapy. In some embodiments, the high-dose radiotherapy is administered as a single dose and/or hypofractionated. In some embodiments, the compound is administered in conjunction with Stereotactic Body Radiation Therapy (SBRT). INCORPORATION BY REFERENCE [0018] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference for the specific purposes identified herein. DETAILED DESCRIPTION OF THE INVENTION Definitions [0019] 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 “an agent” includes a plurality of such agents, and reference to “the cell” includes reference to one or more cells (or to a plurality of cells) and equivalents thereof known to those skilled in the art, and so forth. When ranges are used herein for physical properties, such as molecular weight, or chemical properties, such as chemical formulae, all combinations and subcombinations of ranges and specific embodiments therein are intended to be included. The term “about” when referring to a number or a numerical range means that the number or numerical range referred to is an approximation within experimental variability (or within statistical experimental error), and thus the number or numerical range, in some instances, will vary between 1% and 15% of the stated number or numerical range. The term “comprising” (and related terms such as “comprise” or “comprises” or “having” or “including”) is not intended to exclude that in other certain embodiments, for example, an embodiment of any composition of matter, composition, method, or process, or the like, described herein, “consist of” or “consist essentially of” the described features. [0020] As used in the specification and appended claims, unless specified to the contrary, the following terms have the meaning indicated below. [0021] “Oxo” refers to =O. [0022] “Amine” refers to -NH ₂ ; [0023] “Hydroxyl” refers to -OH; [0024] “Carboxyl” refers to -COOH. [0025] “Alkyl” refers to a straight-chain or branched-chain saturated hydrocarbon monoradical having from one to about ten carbon atoms, more preferably one to six carbon atoms. Examples include, but are not limited to methyl, ethyl, n-propyl, isopropyl, 2-methyl-1-propyl, 2-methyl-2-propyl, 2- methyl-1-butyl, 3-methyl-1-butyl, 2-methyl-3-butyl, 2,2-dimethyl-1-propyl, 2-methyl-1-pentyl, 3-methyl- 1-pentyl, 4-methyl-1-pentyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 2,2-dimethyl-1- butyl, 3,3-dimethyl-1-butyl, 2-ethyl-1-butyl, n-butyl, isobutyl, sec-butyl, t-butyl, n-pentyl, isopentyl, neopentyl, tert-amyl and hexyl, and longer alkyl groups, such as heptyl, octyl and the like. Whenever it appears herein, a numerical range such as “C ₁ -C ₆ alkyl”, means that the alkyl group may consist of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms or 6 carbon atoms, although the present definition also covers the occurrence of the term “alkyl” where no numerical range is designated. In some embodiments, the alkyl is a C1-C10 alkyl. In some embodiments, the alkyl is a C1- C ₆ alkyl. In some embodiments, the alkyl is a C ₁ -C ₅ alkyl. In some embodiments, the alkyl is a C ₁ -C ₄ alkyl. In some embodiments, the alkyl is a C1-C3 alkyl. Unless stated otherwise specifically in the specification, an alkyl group may be optionally substituted, for example, with one or more oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, or heteroaryl, and the like. In some embodiments, the alkyl is optionally substituted with one or more oxo, halogen, -CN, -COOH, -COOMe, -OH, -OMe, -NH2, or -NO2. In some embodiments, the alkyl is optionally substituted with one or more halogen, -CN, -OH, or -OMe. In some embodiments, the alkyl is optionally substituted with halogen. [0026] “Alkenyl” refers to a straight-chain or branched-chain hydrocarbon monoradical having one or more carbon-carbon double-bonds and having from two to about ten carbon atoms, more preferably two to about six carbon atoms. The group may be in either the cis or trans or Z or E conformation about the double bond(s), and should be understood to include both isomers. Examples include, but are not limited to ethenyl (-CH=CH2), 1-propenyl (-CH2CH=CH2), isopropenyl [-C(CH3)=CH2], butenyl, 1,3- butadienyl and the like. Whenever it appears herein, a numerical range such as “C ₂ -C ₆ alkenyl”, means that the alkenyl group may consist of 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms or 6 carbon atoms, although the present definition also covers the occurrence of the term “alkenyl” where no numerical range is designated. Unless stated otherwise specifically in the specification, an alkenyl group may be optionally substituted, for example, with one or more oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, or heteroaryl, and the like. In some embodiments, the alkenyl is optionally substituted with one or more oxo, halogen, -CN, -COOH, -COOMe, -OH, -OMe, -NH ₂ , or -NO ₂ . In some embodiments, the alkenyl is optionally substituted with one or more halogen, -CN, -OH, or -OMe. In some embodiments, the alkenyl is optionally substituted with halogen. [0027] “Alkynyl” refers to a straight-chain or branched-chain hydrocarbon monoradical having one or more carbon-carbon triple-bonds and having from two to about ten carbon atoms, more preferably from two to about six carbon atoms. Examples include, but are not limited to ethynyl, 2-propynyl, 2- butynyl, 1,3-butadiynyl and the like. Whenever it appears herein, a numerical range such as “C2-C6 alkynyl”, means that the alkynyl group may consist of 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms or 6 carbon atoms, although the present definition also covers the occurrence of the term “alkynyl” where no numerical range is designated. Unless stated otherwise specifically in the specification, an alkynyl group may be optionally substituted, for example, with one or more oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, or heteroaryl, and the like. In some embodiments, the alkynyl is optionally substituted with one or more oxo, halogen, -CN, -COOH, -COOMe, -OH, -OMe, -NH ₂ , or -NO ₂ . In some embodiments, the alkynyl is optionally substituted with one or more halogen, -CN, -OH, or -OMe. In some embodiments, the alkynyl is optionally substituted with halogen. [0028] “Alkylene” refers to a straight or branched divalent hydrocarbon chain. Unless stated otherwise specifically in the specification, an alkylene group may be optionally substituted, for example, with one or more oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, or heteroaryl, and the like. In some embodiments, the alkylene is optionally substituted with one or more oxo, halogen, -CN, -COOH, -COOMe, -OH, -OMe, - NH ₂ , or -NO ₂ . In some embodiments, the alkylene is optionally substituted with one or more halogen, - CN, -OH, or -OMe. In some embodiments, the alkylene is optionally substituted with halogen. [0029] “Alkoxy” refers to a radical of the formula -Oalkyl where alkyl is defined as above. Unless stated otherwise specifically in the specification, an alkoxy group may be optionally substituted, for example, with one or more oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, or heteroaryl, and the like. In some embodiments, the alkoxy is optionally substituted with one or more halogen, -CN, -COOH, -COOMe, - OH, -OMe, -NH2, or -NO2. In some embodiments, the alkoxy is optionally substituted with one or more halogen, -CN, -OH, or -OMe. In some embodiments, the alkoxy is optionally substituted with halogen. [0030] “Aminoalkyl” refers to an alkyl radical, as defined above, that is substituted by one or more amines. In some embodiments, the alkyl is substituted with one amine. In some embodiments, the alkyl is substituted with one, two, or three amines. Aminoalkyl include, for example, aminomethyl, aminoethyl, aminopropyl, aminobutyl, or aminopentyl. In some embodiments, the aminoalkyl is aminomethyl. [0031] “Aryl” refers to a radical derived from a hydrocarbon ring system comprising 6 to 30 carbon atoms and at least one aromatic ring. The aryl radical may be a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may include fused (when fused with a cycloalkyl or heterocycloalkyl ring, the aryl is bonded through an aromatic ring atom) or bridged ring systems. In some embodiments, the aryl is a 6- to 10-membered aryl. In some embodiments, the aryl is a 6-membered aryl (phenyl). Aryl radicals include, but are not limited to anthracenyl, naphthyl, phenanthrenyl, azulenyl, phenyl, chrysenyl, fluoranthenyl, fluorenyl, as-indacenyl, s-indacenyl, indanyl, indenyl, phenalenyl, phenanthrenyl, pleiadenyl, pyrenyl, and triphenylenyl. Unless stated otherwise specifically in the specification, an aryl may be optionally substituted, for example, with one or more halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, or heteroaryl, and the like. In some embodiments, the aryl is optionally substituted with one or more halogen, methyl, ethyl, -CN, -COOH, -COOMe, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, the aryl is optionally substituted with one or more halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, the aryl is optionally substituted with halogen. [0032] “Cycloalkyl” refers to a partially or fully saturated, monocyclic, or polycyclic carbocyclic ring, which may include fused (when fused with an aryl or a heteroaryl ring, the cycloalkyl is bonded through a non-aromatic ring atom), spiro, and/or bridged ring systems. In some embodiments, the cycloalkyl is fully saturated. Representative cycloalkyls include, but are not limited to, cycloalkyls having from three to fifteen carbon atoms (e.g., C3-C15 fully saturated cycloalkyl or C3-C15 cycloalkenyl), from three to ten carbon atoms (e.g., C3-C10 fully saturated cycloalkyl or C3-C10 cycloalkenyl), from three to eight carbon atoms (e.g., C3-C8 fully saturated cycloalkyl or C3-C8 cycloalkenyl), from three to six carbon atoms (e.g., C ₃ -C ₆ fully saturated cycloalkyl or C ₃ -C ₆ cycloalkenyl), from three to five carbon atoms (e.g., C3-C5 fully saturated cycloalkyl or C3-C5 cycloalkenyl), or three to four carbon atoms (e.g., C3-C4 fully saturated cycloalkyl or C3-C4 cycloalkenyl). In some embodiments, the cycloalkyl is a 3- to 10-membered fully saturated cycloalkyl or a 3- to 10-membered cycloalkenyl. In some embodiments, the cycloalkyl is a 3- to 6-membered fully saturated cycloalkyl or a 3- to 6-membered cycloalkenyl. In some embodiments, the cycloalkyl is a 5- to 6-membered fully saturated cycloalkyl or a 5- to 6-membered cycloalkenyl. Monocyclic cycloalkyls include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Polycyclic cycloalkyls include, for example, adamantyl, norbornyl, decalinyl, bicyclo[3.3.0]octyl, bicyclo[4.3.0]nonyl, cis-decalinyl, trans-decalinyl, bicyclo[2.1.1]hexyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl, bicyclo[3.2.1]octyl, bicyclo[3.2.2]nonyl, and bicyclo[3.3.2]decyl, bicyclo[1.1.1]pentyl, bicyclo[3.1.0]hexyl, bicyclo[3.1.1]heptyl, 7,7-dimethyl- bicyclo[2.2.1]heptanyl, Spiro[4.2]heptyl, sprio[4.3]octyl, spiro[5.2]octyl, spiro[3.3]heptyl, and spiro[5.3]nonyl. Partially saturated cycloalkyls include, for example cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl. Unless stated otherwise specifically in the specification, a cycloalkyl is optionally substituted, for example, with one or more oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, or heteroaryl, and the like. In some embodiments, a cycloalkyl is optionally substituted with one or more oxo, halogen, methyl, ethyl, -CN, -COOH, -COOMe, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, a cycloalkyl is optionally substituted with one or more oxo, halogen, methyl, ethyl, -CN, - CF ₃ , -OH, or -OMe. In some embodiments, the cycloalkyl is optionally substituted with halogen. [0033] “Halo” or “halogen” refers to bromo, chloro, fluoro or iodo. In some embodiments, halogen is fluoro or chloro. In some embodiments, halogen is fluoro. [0034] “Haloalkyl” refers to an alkyl radical, as defined above, that is substituted by one or more halo radicals, as defined above, e.g., trifluoromethyl, difluoromethyl, fluoromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 1,2-difluoroethyl, 2-fluoroethyl, 3-bromo-2-fluoropropyl, 1,2-dibromoethyl, and the like. [0035] “Haloalkoxy” refers to -O-haloalkyl, with haloalkyl as defined above. [0036] “Hydroxyalkyl” refers to an alkyl radical, as defined above, that is substituted by one or more hydroxyls. In some embodiments, the alkyl is substituted with one hydroxyl. In some embodiments, the alkyl is substituted with one, two, or three hydroxyls. Hydroxyalkyl includes, for example, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, or hydroxypentyl. In some embodiments, the hydroxyalkyl is hydroxymethyl. [0037] “Aminoalkyl” refers to an alkyl radical, as defined above, that is substituted by one or more amines. In some embodiments, the alkyl is substituted with one amine. In some embodiments, the alkyl is substituted with one, two, or three amines. Aminoalkyl includes, for example, aminomethyl, aminoethyl, aminopropyl, aminobutyl, or aminopentyl. In some embodiments, the aminoalkyl is aminomethyl. [0038] “Deuteroalkyl” refers to an alkyl radical, as defined above, that is substituted by one or more deuteriums. In some embodiments, the alkyl is substituted with one deuterium. In some embodiments, the alkyl is substituted with one, two, or three deuteriums. In some embodiments, the alkyl is substituted with one, two, three, four, five, or six deuteriums. Deuteroalkyl includes, for example, CD3, CH2D, CHD2, CH2CD3, CD2CD3, CHDCD3, CH2CH2D, or CH2CHD2. In some embodiments, the deuteroalkyl is CD3. [0039] “Heteroalkyl” refers to an alkyl group in which one or more skeletal atoms of the alkyl are selected from an atom other than carbon, e.g., oxygen, nitrogen, sulfur, phosphorus, or combinations thereof. A heteroalkyl is attached to the rest of the molecule at a carbon atom of the heteroalkyl. In one aspect, a heteroalkyl is a C ₁ -C ₆ heteroalkyl wherein the heteroalkyl is comprised of 1 to 6 carbon atoms and one or more atoms other than carbon, e.g., oxygen, nitrogen, sulfur, phosphorus, or combinations thereof wherein the heteroalkyl is attached to the rest of the molecule at a carbon atom of the heteroalkyl. In one aspect, a heteroalkyl is a C1-C6 heteroalkyl wherein the heteroalkyl is comprised of 1 to 6 carbon atoms and one or two atoms selected from the group consisting of oxygen, nitrogen, and sulfur wherein the heteroalkyl is attached to the rest of the molecule at a carbon atom of the heteroalkyl. Examples of such heteroalkyl are, for example, - Unless stated otherwise specifically in the specification, a heteroalkyl is optionally substituted for example, with one or more oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, or heteroaryl, and the like. In some embodiments, a heteroalkyl is optionally substituted with one or more oxo, halogen, methyl, ethyl, -CN, -CF ₃ , -OH, -OMe, -NH ₂ , or - NO ₂ . In some embodiments, a heteroalkyl is optionally substituted with one or more oxo, halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, the heteroalkyl is optionally substituted with halogen. [0040] “Heterocycloalkyl” refers to a 3- to 24-membered partially or fully saturated ring radical comprising 2 to 23 carbon atoms and from one to 8 heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorous, silicon, and sulfur. In some embodiments, the heterocycloalkyl is fully saturated. In some embodiments, the heterocycloalkyl is C-linked. In some embodiments, the heterocycloalkyl is N-linked. In some embodiments, the heterocycloalkyl comprises one to three heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur. In some embodiments, the heterocycloalkyl comprises one to three heteroatoms selected from the group consisting of nitrogen and oxygen. In some embodiments, the heterocycloalkyl comprises one to three nitrogens. In some embodiments, the heterocycloalkyl comprises one or two nitrogens. In some embodiments, the heterocycloalkyl comprises one nitrogen. In some embodiments, the heterocycloalkyl comprises one nitrogen and one oxygen. Unless stated otherwise specifically in the specification, the heterocycloalkyl radical may be a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may include fused (when fused with an aryl or a heteroaryl ring, the heterocycloalkyl is bonded through a non-aromatic ring atom), spiro, or bridged ring systems; and the nitrogen, carbon, or sulfur atoms in the heterocycloalkyl radical may be optionally oxidized; the nitrogen atom may be optionally quaternized. Representative heterocycloalkyls include, but are not limited to, heterocycloalkyls having from two to fifteen carbon atoms (e.g., C ₂ -C ₁₅ fully saturated heterocycloalkyl or C ₂ -C ₁₅ heterocycloalkenyl), from two to ten carbon atoms (e.g., C2-C10 fully saturated heterocycloalkyl or C2-C10 heterocycloalkenyl), from two to eight carbon atoms (e.g., C2-C8 fully saturated heterocycloalkyl or C2-C8 heterocycloalkenyl), from two to seven carbon atoms (e.g., C2-C7 fully saturated heterocycloalkyl or C2-C7 heterocycloalkenyl), from two to six carbon atoms (e.g., C2-C6 fully saturated heterocycloalkyl or C2-C7 heterocycloalkenyl), from two to five carbon atoms (e.g., C2-C5 fully saturated heterocycloalkyl or C2-C5 heterocycloalkenyl), or two to four carbon atoms (e.g., C ₂ -C ₄ fully saturated heterocycloalkyl or C ₂ -C ₄ heterocycloalkenyl). Examples of such heterocycloalkyl radicals include, but are not limited to, aziridinyl, azetidinyl, oxetanyl, dioxolanyl, thienyl[1,3]dithianyl, decahydroisoquinolyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, trithianyl, tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpholinyl, 1,1-dioxo-thiomorpholinyl, 1,3-dihydroisobenzofuran-1-yl, 3- oxo-1,3-dihydroisobenzofuran-1-yl, methyl-2-oxo-1,3-dioxol-4-yl, and 2-oxo-1,3-dioxol-4-yl. The term heterocycloalkyl also includes all ring forms of the carbohydrates, including but not limited to the monosaccharides, the disaccharides, and the oligosaccharides. In some embodiments, heterocycloalkyls have from 2 to 10 carbons in the ring. It is understood that when referring to the number of carbon atoms in a heterocycloalkyl, the number of carbon atoms in the heterocycloalkyl is not the same as the total number of atoms (including the heteroatoms) that make up the heterocycloalkyl (i.e. skeletal atoms of the heterocycloalkyl ring). In some embodiments, the heterocycloalkyl is a 3- to 8-membered heterocycloalkyl. In some embodiments, the heterocycloalkyl is a 3- to 7-membered heterocycloalkyl. In some embodiments, the heterocycloalkyl is a 3- to 6-membered heterocycloalkyl. In some embodiments, the heterocycloalkyl is a 4- to 6-membered heterocycloalkyl. In some embodiments, the heterocycloalkyl is a 5- to 6-membered heterocycloalkyl. In some embodiments, the heterocycloalkyl is a 3- to 8- membered heterocycloalkenyl. In some embodiments, the heterocycloalkyl is a 3- to 7-membered heterocycloalkenyl. In some embodiments, the heterocycloalkyl is a 3- to 6-membered heterocycloalkenyl. In some embodiments, the heterocycloalkyl is a 4- to 6-membered heterocycloalkenyl. In some embodiments, the heterocycloalkyl is a 5- to 6-membered heterocycloalkenyl. Unless stated otherwise specifically in the specification, a heterocycloalkyl is optionally substituted, for example, with one or more oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, and the like. In some embodiments, the heterocycloalkyl is optionally substituted with one or more oxo, halogen, methyl, ethyl, -CN, -COOH, -COOMe, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, the heterocycloalkyl is optionally substituted with one or more halogen, methyl, ethyl, - CN, -CF3, -OH, or -OMe. In some embodiments, the heterocycloalkyl is optionally substituted with halogen. [0041] “Heteroaryl” refers to a 5- to 14-membered ring system radical comprising one to thirteen carbon atoms, one to six heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorous, and sulfur, and at least one aromatic ring. In some embodiments, the heteroaryl comprises one to three heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur. In some embodiments, the heteroaryl comprises one to three heteroatoms selected from the group consisting of nitrogen and oxygen. In some embodiments, the heteroaryl comprises one to three nitrogens. In some embodiments, the heteroaryl comprises one or two nitrogens. In some embodiments, the heteroaryl comprises one nitrogen. In some embodiments, the heteroaryl is C-linked. In some embodiments, the heteroaryl is N-linked. The heteroaryl radical may be a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may include fused (when fused with a cycloalkyl or heterocycloalkyl ring, the heteroaryl is bonded through an aromatic ring atom) or bridged ring systems; and the nitrogen, carbon, or sulfur atoms in the heteroaryl radical may be optionally oxidized; the nitrogen atom may be optionally quaternized. In some embodiments, the heteroaryl is a 5- to 10-membered heteroaryl. In some embodiments, the heteroaryl is a 5- to 6-membered heteroaryl. In some embodiments, the heteroaryl is a 6-membered heteroaryl. In some embodiments, the heteroaryl is a 5-membered heteroaryl. In some embodiments, the heteroaryl is a 5- to 6-membered ring comprising 1, 2, or 3 heteroatoms selected from the group consisting of oxygen, nitrogen, or sulfur. Examples include, but are not limited to, azepinyl, acridinyl, benzimidazolyl, benzothiazolyl, benzindolyl, benzodioxolyl, benzofuranyl, benzoxazolyl, benzothiadiazolyl, benzo[b][1,4]dioxepinyl, 1,4-benzodioxanyl, benzonaphthofuranyl, benzodioxinyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, benzothienyl (benzothiophenyl), benzotriazolyl, benzo[4,6]imidazo[1,2-a]pyridinyl, carbazolyl, cinnolinyl, dibenzofuranyl, dibenzothiophenyl, furanyl, isothiazolyl, imidazolyl, indazolyl, indolyl, , isoindolyl, indolinyl, isoindolinyl, isoquinolyl, indolizinyl, isoxazolyl, naphthyridinyl, oxadiazolyl, 2-oxoazepinyl, oxazolyl, 1- oxidopyridinyl, 1-oxidopyrimidinyl, 1-oxidopyrazinyl, 1-oxidopyridazinyl, 1-phenyl-1H-pyrrolyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, quinazolinyl, quinoxalinyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, triazinyl, and thiophenyl (i.e., thienyl). Unless stated otherwise specifically in the specification, a heteroaryl is optionally substituted, for example, with one or more halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, or heteroaryl, and the like. In some embodiments, the heteroaryl is optionally substituted with one or more halogen, methyl, ethyl, -CN, - COOH, -COOMe, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, the heteroaryl is optionally substituted with one or more halogen, methyl, ethyl, -CN, -CF ₃ , -OH, or -OMe. In some embodiments, the heteroaryl is optionally substituted with halogen. [0042] The terms “treat,” “ameliorate,” and “inhibit,” as well as words stemming therefrom, as used herein, do not necessarily imply 100% or complete treatment, amelioration, or inhibition. Rather, there are varying degrees of treatment, amelioration, and inhibition of which one of ordinary skill in the art recognizes as having a potential benefit or therapeutic effect. In this respect, the disclosed methods can provide any amount of any level of treatment, amelioration, or inhibition of the disorder in a mammal. For example, a disorder, including symptoms or conditions thereof, may be reduced by, for example, about 100%, about 90%, about 80%, about 70%, about 60%, about 50%, about 40%, about 30%, about 20%, or about 10%. Furthermore, the treatment, amelioration, or inhibition provided by the methods disclosed herein can include treatment, amelioration, or inhibition of one or more conditions or symptoms of the disorder, e.g., cancer or an inflammatory disease. Also, for purposes herein, “treatment,” “amelioration,” or “inhibition” encompass delaying the onset of the disorder, or a symptom or condition thereof. [0043] The terms “effective amount” or “therapeutically effective amount,” as used herein, refer to a sufficient amount of a compound disclosed herein being administered which will relieve to some extent one or more of the symptoms of the disease or condition being treated, e.g., cancer or an inflammatory disease. In some embodiments, the result is a reduction and/or alleviation of the signs, symptoms, or causes of a disease, or any other desired alteration of a biological system. For example, an “effective amount” for therapeutic uses is the amount of the composition comprising a compound disclosed herein required to provide a clinically significant decrease in disease symptoms. In some embodiments, an appropriate “effective” amount in any individual case is determined using techniques, such as a dose escalation study. [0044] The term “one or more” when referring to an optional substituent means that the subject group is optionally substituted with one, two, three, four, or more substituents. In some embodiments, the subject group is optionally substituted with one, two, three, or four substituents. In some embodiments, the subject group is optionally substituted with one, two, or three substituents. In some embodiments, the subject group is optionally substituted with one or two substituents. In some embodiments, the subject group is optionally substituted with one substituent. In some embodiments, the subject group is optionally substituted with two substituents. Compounds [0045] Described herein are compounds that are useful in treating diseases associated with TREX1 and STING dysfunction. In some embodiments, the compounds disclosed herein are TREX1 inhibitors. In some embodiments, the compounds disclosed herein are reversible TREX1 inhibitors. In some embodiments, the compounds disclosed herein are reversible, non-competitive TREX1 inhibitors. [0046] Disclosed herein is a compound of Formula (I), or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof: Formula (I), wherein: Ring A is cycloalkyl, heterocycloalkyl, phenyl, or a 6-membered heteroaryl; each R ¹ is independently halogen, -CN, -NO2, -OH, -OR ^a , -OC(=O)R ^a , -OC(=O)OR ^b , -OC(=O)NR ^c R ^d , - SF5, -SH, -SR ^a , -S(=O)R ^a , -S(=O)2R ^a , -S(=O)2NR ^c R ^d , -S(=O)(=NR ^b )R ^b , -NR ^c R ^d , -NR ^b C(=O)NR ^c R ^d , - NR ^b C(=O)R ^a , -NR ^b C(=O)OR ^b , -NR ^b S(=O)2R ^a , -N=S(=O)(R ^b )2, -C(=O)R ^a , -C(=O)OR ^b , - C(=O)NR ^c R ^d , -P(=O)(R ^b ) ₂ , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ hydroxyalkyl, C ₁ -C ₆ aminoalkyl, C ₁ - C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; n is 0, 1, 2, 3, or 4; X ¹ is -O-, -S-, or -NR ^X1 -; X ² is -N- or -CR ^X2 -; R ^X1 is hydrogen, -S(=O)R ^a , -S(=O) ₂ R ^a , -S(=O) ₂ NR ^c R ^d , -C(=O)R ^a , -C(=O)OR ^b , -C(=O)NR ^c R ^d , C ₁ -C ₆ alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^X1a ; each R ^X1a is independently halogen, -CN, -NO ₂ , -OH, -OR ^a , -OC(=O)R ^a , -OC(=O)OR ^b , -OC(=O)NR ^c R ^d , - SF5, -SH, -SR ^a , -S(=O)R ^a , -S(=O)2R ^a , -S(=O)2NR ^c R ^d , -S(=O)(=NR ^b )R ^b , -NR ^c R ^d , -NR ^b C(=O)NR ^c R ^d , - NR ^b C(=O)R ^a , -NR ^b C(=O)OR ^b , -NR ^b S(=O)2R ^a , -N=S(=O)(R ^b )2, -C(=O)R ^a , -C(=O)OR ^b , - C(=O)NR ^c R ^d , -P(=O)(R ^b ) ₂ , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ hydroxyalkyl, C ₁ -C ₆ aminoalkyl, C ₁ - C6 ^{heteroalkyl, C} 2 ^-C 6 ^{alkenyl, C} 2 ^-C 6 ^{alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein} each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or two R ^X1a on the same atom are taken together to form an oxo; R ^X2 is hydrogen, halogen, -CN, -NO2, -OH, -OR ^a , -NR ^c R ^d , -C(=O)R ^a , -C(=O)OR ^b , -C(=O)NR ^c R ^d , C1- C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2- C ₆ alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; R ² is hydrogen, -C(=O)R ^a , -C(=O)OR ^b , -C(=O)NR ^c R ^d , -CH2OC(=O)OR ^b , -CH(CH3)OC(=O)OR ^b , - C(CH ₃ ) ₂ OC(=O)OR ^b , -CH ₂ OC(=O)R ^a , -CH(CH ₃ )OC(=O)R ^a , -C(CH ₃ ) ₂ OC(=O)R ^a , - CH2OP(=O)(OR ^b )2, -P(=O)(OR ^b )2, -P(=O)(OR ^b )(NR ^b ), C1-C6alkyl, C1-C6haloalkyl, C1- C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, or heterocycloalkyl; R ³ is hydrogen, -S(=O)R ^a , -S(=O) ₂ R ^a , -S(=O) ₂ NR ^c R ^d , -C(=O)R ^a , -C(=O)OR ^b , -C(=O)NR ^c R ^d , C ₁ -C ₆ alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, or heterocycloalkyl; Ring B is bicyclic ring; each R ⁵ is independently halogen, -CN, -NO2, -OH, -OR ^a , -OC(=O)R ^a , -OC(=O)OR ^b , -OC(=O)NR ^c R ^d , - SF5, -SH, -SR ^a , -S(=O)R ^a , -S(=O)2R ^a , -S(=O)2NR ^c R ^d , -S(=O)(=NR ^b )R ^b , -NR ^c R ^d , -NR ^b C(=O)NR ^c R ^d , - NR ^b C(=O)R ^a , -NR ^b C(=O)OR ^b , -NR ^b S(=O)2R ^a , -N=S(=O)(R ^b )2, -C(=O)R ^a , -C(=O)OR ^b , -C(=O)O-C1- C ₆ alkylene-OR ^b , -C(=O)NR ^c R ^d , -C(=O)NR ^c -C ₁ -C ₆ alkylene-OR ^b , -P(=O)(R ^b ) ₂ , C ₁ -C ₆ alkyl, C ₁ - C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or m ^{ore R5a;} or two R ⁵ on the same atom are taken together to form an oxo; each R ^5a is independently halogen, -CN, -NO2, -OH, -OR ^a , -OC(=O)R ^a , -OC(=O)OR ^b , -OC(=O)NR ^c R ^d , - SF ₅ , -SH, -SR ^a , -S(=O)R ^a , -S(=O) ₂ R ^a , -S(=O) ₂ NR ^c R ^d , -S(=O)(=NR ^b )R ^b , -NR ^c R ^d , -NR ^b C(=O)NR ^c R ^d , - NR ^b C(=O)R ^a , -NR ^b C(=O)OR ^b , -NR ^b S(=O)2R ^a , -N=S(=O)(R ^b )2, -C(=O)R ^a , -C(=O)OR ^b , - C(=O)NR ^c R ^d , -P(=O)(R ^b )2, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1- C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or two R ^5a on the same atom are taken together to form an oxo; m is 0, 1, 2, 3, or 4; ^{R6 is hydrogen, -S(=O)Ra, -S(=O)} 2 ^{Ra, -S(=O)} 2 ^{NRcRd, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C} 1 ^-C 6 ^alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6alkylene(cycloalkyl), C1- C ₆ alkylene(heterocycloalkyl), C ₁ -C ₆ alkylene(aryl), or C ₁ -C ₆ alkylene(heteroaryl); wherein the alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^6a ; each R ^6a is independently halogen, -CN, -NO ₂ , -OH, -OR ^a , -OC(=O)R ^a , -OC(=O)OR ^b , -OC(=O)NR ^c R ^d , - SF ₅ , -SH, -SR ^a , -S(=O)R ^a , -S(=O) ₂ R ^a , -S(=O) ₂ NR ^c R ^d , -S(=O)(=NR ^b )R ^b , -NR ^c R ^d , -NR ^b C(=O)NR ^c R ^d , - NR ^b C(=O)R ^a , -NR ^b C(=O)OR ^b , -NR ^b S(=O)2R ^a , -N=S(=O)(R ^b )2, -C(=O)R ^a , -C(=O)OR ^b , - C(=O)NR ^c R ^d , -P(=O)(R ^b )2, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1- C ₆ heteroalkyl, C ₂ -C ₆ alkenyl, C ₂ -C ₆ alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or two R ^6a on the same atom are taken together to form an oxo; R ⁷ is hydrogen, -S(=O)R ^a , -S(=O) ₂ R ^a , -S(=O) ₂ NR ^c R ^d , -C(=O)R ^a , -C(=O)OR ^b , -C(=O)NR ^c R ^d , C ₁ -C ₆ alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each R ^a is independently C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1- C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1- C6alkylene(cycloalkyl), C1-C6alkylene(heterocycloalkyl), C1-C6alkylene(aryl), or C1- C ₆ alkylene(heteroaryl); wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each R ^b is independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C ₁ -C ₆ heteroalkyl, C ₂ -C ₆ alkenyl, C ₂ -C ₆ alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C ₁ - C6 ^{alkylene(cycloalkyl), C} 1 ^-C 6 ^{alkylene(heterocycloalkyl), C} 1 ^-C 6 ^{alkylene(aryl), or C} 1- C6alkylene(heteroaryl); wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; R ^c and R ^d are each independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ hydroxyalkyl, C ₁ - C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6alkylene(cycloalkyl), C1-C6alkylene(heterocycloalkyl), C1-C6alkylene(aryl), or C1- C6alkylene(heteroaryl); wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or R ^c and R ^d are taken together with the atom to which they are attached to form a heterocycloalkyl independently optionally substituted with one or more R; and each R is independently halogen, -CN, -OH, -SF ₅ , -SH, -S(=O)C ₁ -C ₃ alkyl, -S(=O) ₂ C ₁ -C ₃ alkyl, - S ^(=O) 2 ^NH 2 ^{, -S(=O)} 2 ^NHC 1 ^-C 3 ^{alkyl, -S(=O)} 2 ^N(C 1 ^-C 3 ^alkyl) 2 ^{, -S(=O)(=NC} 1 ^-C 3 ^alkyl)(C 1 ^-C 3 ^{alkyl), -} NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, -N=S(=O)(C1-C3alkyl)2, -C(=O)C1-C3alkyl, -C(=O)OH, - C(=O)OC1-C3alkyl, -C(=O)NH2, -C(=O)NHC1-C3alkyl, -C(=O)N(C1-C3alkyl)2, -P(=O)(C1-C3alkyl)2, C ₁ -C ₃ alkyl, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkyl, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ hydroxyalkyl, C ₁ -C ₃ aminoalkyl, C1-C3heteroalkyl, or C3-C6cycloalkyl; or two R on the same atom form an oxo. [0047] In some embodiments of a compound of Formula (I), the compound is of Formula (Ia): Formula (Ia). [0048] In some embodiments of a compound of Formula (I) or (Ia), Ring B is a bicyclic heteroaryl or bicyclic heterocycloalkyl. [0049] In some embodiments of a compound of Formula (I) or (Ia), Ring B is a 8- to 12-membered bicyclic heteroaryl or a 8- to 12-membered bicyclic heterocycloalkyl; wherein the heteroaryl or heterocycloalkyl comprises one to four heteroatoms selected from the group consisting of O, S, and N. [0050] In some embodiments of a compound of Formula (I) or (Ia), Ring B is a 8- to 12-membered bicyclic heteroaryl or a 8- to 12-membered bicyclic heterocycloalkyl; wherein the heteroaryl or heterocycloalkyl comprises one to three heteroatoms selected from the group consisting of O, S, and N. In some embodiments of a compound of Formula (I) or (Ia), Ring B is a 8- to 12-membered bicyclic heteroaryl or a 8- to 12-membered bicyclic heterocycloalkyl; wherein the heteroaryl or heterocycloalkyl comprises one to two heteroatoms selected from the group consisting of O, S, and N. [0051] In some embodiments of a compound of Formula (I) or (Ia), Ring B is a 8- to 12-membered bicyclic heteroaryl or a 8- to 12-membered bicyclic heterocycloalkyl; wherein the heteroaryl or heterocycloalkyl comprises one to two heteroatoms selected from the group consisting of O and N. [0052] In some embodiments of a compound of Formula (I) or (Ia), Ring B is a bicyclic heteroaryl. [0053] In some embodiments of a compound of Formula (I) or (Ia), Ring B is a 8- to 12-membered bicyclic heteroaryl comprising one to four heteroatoms selected from the group consisting of O, S, and N. [0054] In some embodiments of a compound of Formula (I) or (Ia), Ring B is a 8- to 12-membered bicyclic heteroaryl comprising one to three heteroatoms selected from the group consisting of O, S, and N. [0055] In some embodiments of a compound of Formula (I) or (Ia), Ring B is a 8- to 12-membered bicyclic heteroaryl comprising one to two heteroatoms selected from the group consisting of O and N. [0056] In some embodiments of a compound of Formula (I) or (Ia), Ring B is benzimidazole, benzoxazole, or benzothiazole. In some embodiments of a compound of Formula (I) or (Ia), Ring B is benzimidazole. [0057] In some embodiments of a compound of Formula (I) or (Ia), Ring B is a bicyclic heterocycloalkyl. [0058] In some embodiments of a compound of Formula (I) or (Ia), Ring B is a 8- to 12-membered bicyclic heterocycloalkyl comprising one to four heteroatoms selected from the group consisting of O, S, and N. [0059] In some embodiments of a compound of Formula (I) or (Ia), Ring B is a 8- to 12-membered bicyclic heterocycloalkyl comprising one to three heteroatoms selected from the group consisting of O, S, and N. [0060] In some embodiments of a compound of Formula (I) or (Ia), Ring B is a 8- to 12-membered bicyclic heterocycloalkyl comprising one to two heteroatoms selected from the group consisting of O and N. [0061] In some embodiments of a compound of Formula (I) or (Ia), Ring B is isoindolinyl, tetrahydroisoquinolinyl, or tetrahydrobenzoazepinyl. In some embodiments of a compound of Formula (I) or (Ia), Ring B is tetrahydroisoquinolinyl. [0062] In some embodiments of a compound of Formula (I) or (Ia), each R ⁵ is independently halogen, -CN, -NO ₂ , -OH, -OR ^a , -OC(=O)R ^a , -OC(=O)OR ^b , -OC(=O)NR ^c R ^d , -SF ₅ , -SH, -SR ^a , -S(=O)R ^a , - S(=O) ₂ R ^a , -S(=O) ₂ NR ^c R ^d , -S(=O)(=NR ^b )R ^b , -NR ^c R ^d , -NR ^b C(=O)NR ^c R ^d , -NR ^b C(=O)R ^a , -NR ^b C(=O)OR ^b , -NR ^b S(=O)2R ^a , -N=S(=O)(R ^b )2, -C(=O)R ^a , -C(=O)OR ^b , -C(=O)NR ^c R ^d , -P(=O)(R ^b )2, C1-C6alkyl, C1- C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^5a . _[0063] In some embodiments of a compound of Formula (I) or (Ia), each R ⁵ is independently halogen, -CN, -OH, -OR ^a , -NR ^c R ^d , -NR ^b C(=O)NR ^c R ^d , -NR ^b C(=O)R ^a , -NR ^b C(=O)OR ^b , -C(=O)R ^a , -C(=O)OR ^b , - C(=O)NR ^c R ^d , C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^5a . [0064] In some embodiments of a compound of Formula (I) or (Ia), each R ⁵ is independently halogen, -NR ^c R ^d , -NR ^b C(=O)NR ^c R ^d , -NR ^b C(=O)R ^a , -NR ^b C(=O)OR ^b , -C(=O)R ^a , -C(=O)OR ^b , -C(=O)NR ^c R ^d , C1- C6alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^5a . _[0065] In some embodiments of a compound of Formula (I) or (Ia), each R ⁵ is independently - NR ^b C(=O)NR ^c R ^d , -NR ^b C(=O)R ^a , -NR ^b C(=O)OR ^b , -C(=O)OR ^b , -C(=O)NR ^c R ^d , C1-C6alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^5a . [0066] In some embodiments of a compound of Formula (I) or (Ia), each R ⁵ is independently - ^{C(=O)ORb, -C(=O)NRcRd, C} 1 ^-C 6 ^{alkyl, cycloalkyl, aryl, or heteroaryl; wherein each cycloalkyl, aryl, and} heteroaryl is independently optionally substituted with one or more R ^5a . [0067] In some embodiments of a compound of Formula (I) or (Ia), each R ⁵ is independently - C(=O)OR ^b , -C(=O)NR ^c R ^d , or aryl;wherein each aryl is independently optionally substituted with one or more R ^5a . [0068] In some embodiments of a compound of Formula (I) or (Ia), each R ⁵ is independently halogen, -CN, -OH, -OR ^a , -NR ^c R ^d , -C(=O)R ^a , -C(=O)OR ^b , -C(=O)NR ^c R ^d , C1-C6alkyl, C1-C6haloalkyl, C1- C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^5a . In some embodiments of a compound of Formula (I) or (Ia), each R ⁵ is independently halogen, -OH, -OR ^a , -NR ^c R ^d , C1-C6alkyl, C1-C6haloalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^5a . In some embodiments of a compound of Formula (I) or (Ia), each R ⁵ is independently halogen, C1-C6alkyl, C1-C6haloalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^5a . In some embodiments of a compound of Formula (I) or (Ia), each R ⁵ is independently cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^5a . In some embodiments of a compound of Formula (I) or (Ia), each R ⁵ is independently cycloalkyl, aryl, or heteroaryl; wherein each cycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^5a . In some embodiments of a compound of Formula (I) or (Ia), each R ⁵ is independently cycloalkyl or heterocycloalkyl; wherein each cycloalkyl and heterocycloalkyl is independently optionally substituted with one or more R ^5a . In some embodiments of a compound of Formula (I) or (Ia), each R ⁵ is independently cycloalkyl or heterocycloalkyl. In some embodiments of a compound of Formula (I) or (Ia), each R ⁵ is independently aryl or heteroaryl; wherein each aryl and heteroaryl is independently optionally substituted with one or more R ^5a . In some embodiments of a compound of Formula (I) or (Ia), ^{each R5 is independently aryl or heteroaryl.} [0069] In some embodiments of a compound of Formula (I) or (Ia), each R ^5a is independently halogen, -CN, -OH, -OR ^a , -NR ^c R ^d , -C(=O)R ^a , -C(=O)OR ^b , -C(=O)NR ^c R ^d , C1-C6alkyl, C1-C6haloalkyl, C1- C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, cycloalkyl, or heterocycloalkyl; wherein each alkyl, cycloalkyl, or heterocycloalkyl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (I) or (Ia), each R ^5a is independently halogen, -CN, -OH, -OR ^a , - NR ^c R ^d , C1-C6alkyl, C1-C6haloalkyl, cycloalkyl, or heterocycloalkyl; wherein each alkyl, cycloalkyl, or heterocycloalkyl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (I) or (Ia), each R ^5a is independently halogen, -CN, -OH, -OR ^a , -NR ^c R ^d , C ₁ - C6alkyl, or C1-C6haloalkyl; wherein each alkyl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (I) or (Ia), each R ^5a is independently halogen, -CN, - OH, -OR ^a , -NR ^c R ^d , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, or heterocycloalkyl. In some embodiments of ^{a compound of Formula (I) or (Ia), each R5a is independently halogen, -CN, -OH, -ORa, -NRcRd, C} 1- C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (I) or (Ia), each R ^5a is independently halogen, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (I) or (Ia), each R ^5a is independently halogen or C ₁ -C ₆ alkyl. In some embodiments of a compound of Formula (I) or (Ia), each R ^5a is independently halogen, -CN, -OR ^a , or C1-C6alkyl. In some embodiments of a compound of Formula (I) or (Ia), each R ^5a is independently halogen, -OR ^a , or C1-C6alkyl. In some embodiments of a compound of Formula (I) or (Ia), each R ^5a is independently halogen. [0070] In some embodiments of a compound of Formula (I) or (Ia), each R ⁵ is independently , , [0071] In some embodiments of a compound of Formula (I) or (Ia), m is 0, 1, 2, or 3. In some embodiments of a compound of Formula (I) or (Ia), m is 0, 1, or 2. In some embodiments of a compound of Formula (I) or (Ia), m is 1 or 2. In some embodiments of a compound of Formula (I) or (Ia), m is 0 or 1. In some embodiments of a compound of Formula (I) or (Ia), m is 0. In some embodiments of a compound of Formula (I) or (Ia), m is 1. In some embodiments of a compound of Formula (I) or (Ia), m is 2. In some embodiments of a compound of Formula (I) or (Ia), m is 3. [0072] In some embodiments of a compound of Formula (I) or (Ia), the compound is of Formula (Ia- 1): Formula (Ia-1); wherein: each R ¹⁰ is independently halogen, -CN, -NO2, -OH, -OR ^a , -OC(=O)R ^a , -OC(=O)OR ^b , -OC(=O)NR ^c R ^d , - SF5, -SH, -SR ^a , -S(=O)R ^a , -S(=O)2R ^a , -S(=O)2NR ^c R ^d , -S(=O)(=NR ^b )R ^b , -NR ^c R ^d , -NR ^b C(=O)NR ^c R ^d , - NR ^b C(=O)R ^a , -NR ^b C(=O)OR ^b , -NR ^b S(=O) ₂ R ^a , -N=S(=O)(R ^b ) ₂ , -C(=O)R ^a , -C(=O)OR ^b , - C(=O)NR ^c R ^d , -P(=O)(R ^b )2, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1- C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^10a ; each R ^10a is independently halogen, -CN, -NO2, -OH, -OR ^a , -OC(=O)R ^a , -OC(=O)OR ^b , -OC(=O)NR ^c R ^d , - SF5, -SH, -SR ^a , -S(=O)R ^a , -S(=O)2R ^a , -S(=O)2NR ^c R ^d , -S(=O)(=NR ^b )R ^b , -NR ^c R ^d , -NR ^b C(=O)NR ^c R ^d , - NR ^b C(=O)R ^a , -NR ^b C(=O)OR ^b , -NR ^b S(=O)2R ^a , -N=S(=O)(R ^b )2, -C(=O)R ^a , -C(=O)OR ^b , - C(=O)NR ^c R ^d , -P(=O)(R ^b )2, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1- C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or two R ^10a on the same atom are taken together to form an oxo; s is 0, 1, or 2; each R ¹¹ is independently halogen, -CN, -NO2, -OH, -OR ^a , -OC(=O)R ^a , -OC(=O)OR ^b , -OC(=O)NR ^c R ^d , - SF5, -SH, -SR ^a , -S(=O)R ^a , -S(=O)2R ^a , -S(=O)2NR ^c R ^d , -S(=O)(=NR ^b )R ^b , -NR ^c R ^d , -NR ^b C(=O)NR ^c R ^d , - NR ^b C(=O)R ^a , -NR ^b C(=O)OR ^b , -NR ^b S(=O)2R ^a , -N=S(=O)(R ^b )2, -C(=O)R ^a , -C(=O)OR ^b , -C(=O)O-C1- C ₆ alkylene-OR ^b , -C(=O)NR ^c R ^d , -C(=O)NR ^c -C ₁ -C ₆ alkylene-OR ^b , -P(=O)(R ^b ) ₂ , C ₁ -C ₆ alkyl, C ₁ - C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or m ^{ore R11a;} each R ^11a is independently halogen, -CN, -NO2, -OH, -OR ^a , -OC(=O)R ^a , -OC(=O)OR ^b , -OC(=O)NR ^c R ^d , - C(=O)NR ^c R ^d , -P(=O)(R ^b )2, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1- C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; and t is 0, 1, or 2. [0073] In some embodiments of a compound of Formula (Ia-1), each R ¹⁰ is independently halogen, - CN, -OH, -OR ^a , -NR ^c R ^d , C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1- C ₆ heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, ^{heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R10a.} [0074] In some embodiments of a compound of Formula (Ia-1), each R ¹⁰ is independently halogen, C1-C6alkyl, C1-C6haloalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^10a . _[0075] In some embodiments of a compound of Formula (Ia-1), each R ¹⁰ is independently C ₁ -C ₆ alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^10a . [0076] In some embodiments of a compound of Formula (Ia-1), each R ¹⁰ is independently cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^10a . [0077] In some embodiments of a compound of Formula (Ia-1), each R ¹⁰ is independently aryl or heteroaryl; wherein each aryl and heteroaryl is independently optionally substituted with one or more R ^10a . [0078] In some embodiments of a compound of Formula (Ib), each R ¹⁰ is independently phenyl independently optionally substituted with one or more R ^10a . [0079] In some embodiments of a compound of Formula (Ia-1), each R ^10a is independently halogen, - CN, -OH, -OR ^a , -NR ^c R ^d , -C(=O)R ^a , -C(=O)OR ^b , -C(=O)NR ^c R ^d , C1-C6alkyl, C1-C6haloalkyl, C1- C6hydroxyalkyl, C1-C6aminoalkyl, or C1-C6heteroalkyl. [0080] In some embodiments of a compound of Formula (Ia-1), each R ^10a is independently halogen, - CN, -OH, -OR ^a , -NR ^c R ^d , -C(=O)R ^a , -C(=O)OR ^b , -C(=O)NR ^c R ^d , or C ₁ -C ₆ alkyl. [0081] In some embodiments of a compound of Formula (Ia-1), each R ^10a is independently halogen, - CN, -OH, -OR ^a , -NR ^c R ^d , -C(=O)OR ^b , -C(=O)NR ^c R ^d , or C ₁ -C ₆ alkyl. [0082] ^{In some embodiments of a compound of Formula (Ia-1), each R10a is independently halogen, -} CN, -OR ^a , -C(=O)OR ^b , or C1-C6alkyl. [0083] In some embodiments of a compound of Formula (Ia-1), each R ^10a is independently halogen. [0084] In some embodiments of a compound of Formula (Ia-1), each R ¹⁰ is independently , , , , , . In some embodiments of a compound of Formula (Ia- 1), each R ¹⁰ is independently . In some embodiments of a compound of Formula (Ia-1), each R ¹⁰ is independently , , , . In some embodiments of a compound of Formula (Ia- 1), each R ¹⁰ is independently . In some embodiments of a compound of Formula (Ia-1), each R ¹⁰ is independently . In some embodiments of a compound of Formula (Ia-1), each R ¹⁰ is In some embodiments of a compound of Formula (Ia-1), each R ¹⁰ is [0085] In some embodiments of a compound of Formula (Ia-1), s is 0 or 1. In some embodiments of a compound of Formula (Ia-1), s is 1 or 2. In some embodiments of a compound of Formula (Ia-1), s is 0. In some embodiments of a compound of Formula (Ia-1), s is 1. In some embodiments of a compound of Formula (Ia-1), s is 2. [0086] In some embodiments of a compound of Formula (Ia-1), each R ¹¹ is independently halogen, - CN, -OH, -OR ^a , -NR ^c R ^d , -NR ^b C(=O)NR ^c R ^d , -NR ^b C(=O)R ^a , -NR ^b C(=O)OR ^b , -C(=O)R ^a , -C(=O)OR ^b , - C(=O)NR ^c R ^d , -C(=O)NR ^c -C1-C6alkylene-OR ^b , C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1- C6aminoalkyl, or C1-C6heteroalkyl. [0087] In some embodiments of a compound of Formula (Ia-1), each R ¹¹ is independently halogen, - CN, -OH, -OR ^a , -NR ^c R ^d , -NR ^b C(=O)NR ^c R ^d , -NR ^b C(=O)R ^a , -NR ^b C(=O)OR ^b , -C(=O)R ^a , -C(=O)OR ^b , - C(=O)NR ^c R ^d , C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, or C1-C6heteroalkyl. [0088] In some embodiments of a compound of Formula (Ia-1), each R ¹¹ is independently halogen, - NR ^c R ^d , -NR ^b C(=O)NR ^c R ^d , -NR ^b C(=O)R ^a , -NR ^b C(=O)OR ^b , -C(=O)OR ^b , or -C(=O)NR ^c R ^d . [0089] In some embodiments of a compound of Formula (Ia-1), each R ¹¹ is independently - NR ^b C(=O)NR ^c R ^d , -NR ^b C(=O)R ^a , -NR ^b C(=O)OR ^b , -C(=O)OR ^b , or -C(=O)NR ^c R ^d . [0090] In some embodiments of a compound of Formula (Ia-1), each R ¹¹ is independently -C(=O)OR ^b or -C(=O)NR ^c R ^d . [0091] In some embodiments of a compound of Formula (Ia-1), each R ¹¹ is independently -C(=O)OR ^b . [0092] In some embodiments of a compound of Formula (Ia-1), each R ¹¹ is independently - C(=O)NR ^c R ^d . [0093] In some embodiments of a compound of Formula (Ia-1), t is 0 or 1. In some embodiments of a compound of Formula (Ia-1), t is 1 or 2. In some embodiments of a compound of Formula (Ia-1), t is 0. In some embodiments of a compound of Formula (Ia-1), t is 1. In some embodiments of a compound of Formula (Ia-1), t is 2. [0094] In some embodiments of a compound of Formula (Ia-1), each R ¹¹ is independently , independently . In some embodiments of a compound of Formula (Ia-1), each R ¹¹ is independently . In some embodiments of a compound of Formula (Ia-1), each R ¹¹ is independently . In some embodiments of a compound of Formula (Ia-1), each R ¹¹ is independently . In some embodiments of a compound of Formula (Ia-1), each R ¹¹ is independently . In some embodiments of a compound of Formula (Ia-1), each R ¹¹ is independently In some embodiments of a compound of Formula (Ia-1), each R ¹¹ is independently . In some embodiments of a compound of Formula (Ia-1), each R ¹¹ is independently . In some embodiments of a compound of Formula (Ia-1), each R ¹¹ is independently . In some embodiments of a compound of Formula (Ia-1), each R ¹¹ is independently . In some embodiments of a compound of Formula (Ia-1), each R ¹¹ is independently . In some embodiments of a compound of Formula (Ia-1), each R ¹¹ is independently . [0095] In some embodiments of a compound of Formula (Ia-1), the compound has the following formula: some embodiments of a compound of Formula (Ia-1), some embodiments of a compound of Formula (Ia-1), the compound has the following formula: some embodiments of a compound of Formula (Ia-1), the some embodiments of a compound of Formula (Ia-1), the compound has the following formula:

[0096] In some embodiments of a compound of Formula (I), the compound is of Formula (Ib): Formula (Ib). [0097] In some embodiments of a compound of Formula (I) or (Ib), R ⁶ is cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6alkylene(cycloalkyl), C1-C6alkylene(heterocycloalkyl), C1-C6alkylene(aryl), or C1- C6alkylene(heteroaryl); wherein the alkylene, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^6a . [0098] In some embodiments of a compound of Formula (I) or (Ib), R ⁶ is C1-C6alkylene(cycloalkyl), C ₁ -C ₆ alkylene(heterocycloalkyl), C ₁ -C ₆ alkylene(aryl), or C ₁ -C ₆ alkylene(heteroaryl); wherein the alkylene, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^6a . [0099] In some embodiments of a compound of Formula (I) or (Ib), R ⁶ is C1-C6alkylene(cycloalkyl) or C ₁ -C ₆ alkylene(aryl); wherein the alkylene, cycloalkyl, and aryl is independently optionally substituted with one or more R ^6a . [00100] In some embodiments of a compound of Formula (I) or (Ib), R ⁶ is C1-C6alkylene(aryl); wherein the alkylene and aryl is independently optionally substituted with one or more R ^6a . [00101] In some embodiments of a compound of Formula (I) or (Ib), R ⁶ is C1-C6alkylene(cycloalkyl); wherein the alkylene and cycloalkyl is optionally substituted with one or more R ^6a . [00102] In some embodiments of a compound of Formula (I) or (Ib), each R ^6a is independently halogen, -CN, -OH, -OR ^a , -NR ^c R ^d , -NR ^b S(=O)2R ^a , -C(=O)R ^a , -C(=O)OR ^b , -C(=O)NR ^c R ^d , C1-C6alkyl, C1- C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (I) or (Ib), each R ^6a is independently halogen, -CN, -OH, -OR ^a , -NR ^c R ^d , -NR ^b S(=O)2R ^a , -C(=O)R ^a , -C(=O)OR ^b , - C(=O)NR ^c R ^d , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (I) or (Ib), each R ^6a is independently halogen, -CN, -NR ^b S(=O) ₂ R ^a , -C(=O)OR ^b , -C(=O)NR ^c R ^d , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (I) or (Ib), each R ^6a is independently halogen, -CN, -NR ^b S(=O)2R ^a , -C(=O)OR ^b , - C(=O)NR ^c R ^d , cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (I) or (Ib), each R ^6a is independently halogen, -CN, - NR ^b S(=O)2R ^a , -C(=O)OR ^b , -C(=O)NR ^c R ^d , cycloalkyl, aryl, or heteroaryl; wherein each cycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (I) or (Ib), each R ^6a is independently halogen, -CN, -NR ^b S(=O)2R ^a , -C(=O)OR ^b , - C(=O)NR ^c R ^d , or cycloalkyl; wherein each cycloalkyl is independently optionally substituted with one or more R. [00103] In some embodiments of a compound of Formula (I) or (Ib), the compound is of Formula (Ic): Formula (Ic); wherein: Ring C is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; each R ⁸ is independently halogen, -CN, -OH, -SF5, -SH, -S(=O)C1-C3alkyl, -S(=O)2C1-C3alkyl, - S(=O)2NH2, -S(=O)2NHC1-C3alkyl, -S(=O)2N(C1-C3alkyl)2, -S(=O)(=NC1-C3alkyl)(C1-C3alkyl), - NH ₂ , -NHC ₁ -C ₃ alkyl, -N(C ₁ -C ₃ alkyl) ₂ , -N=S(=O)(C ₁ -C ₃ alkyl) ₂ , -C(=O)C ₁ -C ₃ alkyl, -C(=O)OH, - C(=O)OC1-C3alkyl, -C(=O)NH2, -C(=O)NHC1-C3alkyl, -C(=O)N(C1-C3alkyl)2, -P(=O)(C1-C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3haloalkoxy, C1-C3hydroxyalkyl, C1-C3aminoalkyl, C1-C3heteroalkyl, or C3-C6cycloalkyl; p is 0, 1, 2, 3, or 4; Ring D is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; each R ⁹ is independently halogen, -CN, -NO2, -OH, -OR ^a , -OC(=O)R ^a , -OC(=O)OR ^b , -OC(=O)NR ^c R ^d , - SF5, -SH, -SR ^a , -S(=O)R ^a , -S(=O)2R ^a , -S(=O)2NR ^c R ^d , -S(=O)(=NR ^b )R ^b , -NR ^c R ^d , -NR ^b C(=O)NR ^c R ^d , - NR ^b C(=O)R ^a , -NR ^b C(=O)OR ^b , -NR ^b S(=O)2R ^a , -N=S(=O)(R ^b )2, -C(=O)R ^a , -C(=O)OR ^b , - C(=O)NR ^c R ^d , -P(=O)(R ^b ) ₂ , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ hydroxyalkyl, C ₁ -C ₆ aminoalkyl, C ₁ - C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; ^{or two R9 on the same atom are taken together to form an oxo; and} q is 0, 1, 2, 3, or 4. [00104] In some embodiments of a compound of Formula (Ic), Ring C is cycloalkyl or heterocycloalkyl. In some embodiments of a compound of Formula (Ic), Ring C is aryl or heteroaryl. In some embodiments of a compound of Formula (Ic), Ring C is cycloalkyl or aryl. In some embodiments of a compound of Formula (Ic), Ring C is cycloalkyl. In some embodiments of a compound of Formula (Ic), Ring C is aryl. In some embodiments of a compound of Formula (Ic), Ring C is phenyl. [00105] In some embodiments of a compound of Formula (Ic), each R ⁸ is independently halogen, -CN, -OH, -NH ₂ , -NHC ₁ -C ₃ alkyl, -N(C ₁ -C ₃ alkyl) ₂ , -C(=O)C ₁ -C ₃ alkyl, -C(=O)OH, -C(=O)OC ₁ -C ₃ alkyl, - C(=O)NH ₂ , -C(=O)NHC ₁ -C ₃ alkyl, -C(=O)N(C ₁ -C ₃ alkyl) ₂ , C ₁ -C ₃ alkyl, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkyl, C ₁ - C3haloalkoxy, C1-C3hydroxyalkyl, C1-C3aminoalkyl, C1-C3heteroalkyl, or C3-C6cycloalkyl. In some embodiments of a compound of Formula (Ic), each R ⁸ is independently halogen, -CN, -OH, -NH2, - NHC ₁ -C ₃ alkyl, -N(C ₁ -C ₃ alkyl) ₂ , C ₁ -C ₃ alkyl, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkyl, C ₁ -C ₃ haloalkoxy, C ₁ - C3hydroxyalkyl, C1-C3aminoalkyl, C1-C3heteroalkyl, or C3-C6cycloalkyl. In some embodiments of a compound of Formula (Ic), each R ⁸ is independently halogen, -CN, -OH, -NH2, -NHC1-C3alkyl, -N(C1- C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, or C1-C3haloalkoxy. In some embodiments of a compound of Formula (Ic), each R ⁸ is independently halogen, -CN, -OH, -NH ₂ , C ₁ -C ₃ alkyl, or C ₁ - C3haloalkyl. In some embodiments of a compound of Formula (Ic), each R ⁸ is independently halogen, C1- C3alkyl, or C1-C3haloalkyl. In some embodiments of a compound of Formula (Ic), each R ⁸ is independently halogen or C ₁ -C ₃ alkyl. [00106] In some embodiments of a compound of Formula (Ic), p is 0, 1, or 2. In some embodiments of a compound of Formula (Ic), p is 0 or 1. In some embodiments of a compound of Formula (Ic), p is 1 or 2. In some embodiments of a compound of Formula (Ic), p is 0. In some embodiments of a compound of Formula (Ic), p is 1. In some embodiments of a compound of Formula (Ic), p is 2. In some embodiments of a compound of Formula (Ic), p is 3. [00107] In some embodiments of a compound of Formula (Ic), Ring D is cycloalkyl or heterocycloalkyl. In some embodiments of a compound of Formula (Ic), Ring D is aryl or heteroaryl. In some embodiments of a compound of Formula (Ic), Ring D is cycloalkyl or aryl. In some embodiments of a compound of Formula (Ic), Ring D is cycloalkyl. In some embodiments of a compound of Formula (Ic), Ring D is aryl. In some embodiments of a compound of Formula (Ic), Ring D is phenyl. [00108] In some embodiments of a compound of Formula (Ic), each R ⁹ is independently halogen, -CN, -OH, -OR ^a , -NR ^c R ^d , -NR ^b S(=O)2R ^a , -C(=O)R ^a , -C(=O)OR ^b , -C(=O)NR ^c R ^d , C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (Ic), each R ⁹ is independently halogen, -CN, -OH, -OR ^a , -NR ^c R ^d , -NR ^b S(=O)2R ^a , -C(=O)R ^a , -C(=O)OR ^b , -C(=O)NR ^c R ^d , C1-C6alkyl, C1-C6haloalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (Ic), each R ⁹ is independently halogen, -CN, - OH, -OR ^a , -NR ^c R ^d , -NR ^b S(=O)2R ^a , -C(=O)R ^a , -C(=O)OR ^b , -C(=O)NR ^c R ^d , C1-C6alkyl, or C1-C6haloalkyl; wherein each alkyl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (Ic), each R ⁹ is independently halogen, -CN, -OH, -OR ^a , -NR ^c R ^d , -NR ^b S(=O) ₂ R ^a , -C(=O)R ^a , -C(=O)OR ^b , or -C(=O)NR ^c R ^d . In some embodiments of a compound of Formula (Ic), each R ⁹ is independently halogen, -CN, -NR ^b S(=O)2R ^a , -C(=O)OR ^b , or -C(=O)NR ^c R ^d . [00109] In some embodiments of a compound of Formula (Ic), q is 0, 1, or 2. In some embodiments of a compound of Formula (Ic), q is 0 or 1. In some embodiments of a compound of Formula (Ic), q is 1 or 2. In some embodiments of a compound of Formula (Ic), q is 0. In some embodiments of a compound of Formula (Ic), q is 1. In some embodiments of a compound of Formula (Ic), q is 2. In some embodiments of a compound of Formula (Ic), q is 3. [00110] In some embodiments of a compound of Formula (Ic), the compound has the following formula: . In some embodiments of a compound of Formula (Ic), the [00111] Also disclosed herein is compound of Formula (II), or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof: Formula (II), wherein: Ring A is cycloalkyl, heterocycloalkyl, phenyl, or a 6-membered heteroaryl; ^{each R1 is independently halogen, -CN, -NO} 2 ^{, -OH, -ORa, -OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -} C(=O)NR ^c R ^d , -P(=O)(R ^b ) ₂ , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ hydroxyalkyl, C ₁ -C ₆ aminoalkyl, C ₁ - C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; n is 0, 1, 2, 3, or 4; X ¹ is -O-, -S-, or -NR ^X1 -; X ² is -N- or -CR ^X2 -; R ^X1 is hydrogen, -S(=O)R ^a , -S(=O) ₂ R ^a , -S(=O) ₂ NR ^c R ^d , -C(=O)R ^a , -C(=O)OR ^b , -C(=O)NR ^c R ^d , C ₁ -C ₆ alkyl, C1 ^-C 6 ^{haloalkyl, C} 1 ^-C 6 ^{hydroxyalkyl, C} 1 ^-C 6 ^{aminoalkyl, C} 1 ^-C 6 ^{heteroalkyl, C} 2 ^-C 6 ^{alkenyl, C} 2 ^-C 6 ^alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^X1a ; each R ^X1a is independently halogen, -CN, -NO ₂ , -OH, -OR ^a , -OC(=O)R ^a , -OC(=O)OR ^b , -OC(=O)NR ^c R ^d , - SF5, -SH, -SR ^a , -S(=O)R ^a , -S(=O)2R ^a , -S(=O)2NR ^c R ^d , -S(=O)(=NR ^b )R ^b , -NR ^c R ^d , -NR ^b C(=O)NR ^c R ^d , - NR ^b C(=O)R ^a , -NR ^b C(=O)OR ^b , -NR ^b S(=O)2R ^a , -N=S(=O)(R ^b )2, -C(=O)R ^a , -C(=O)OR ^b , - C(=O)NR ^c R ^d , -P(=O)(R ^b ) ₂ , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ hydroxyalkyl, C ₁ -C ₆ aminoalkyl, C ₁ - C ₆ heteroalkyl, C ₂ -C ₆ alkenyl, C ₂ -C ₆ alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or two R ^X1a on the same atom are taken together to form an oxo; R ^X2 is hydrogen, halogen, -CN, -NO2, -OH, -OR ^a , -NR ^c R ^d , -C(=O)R ^a , -C(=O)OR ^b , -C(=O)NR ^c R ^d , C1- C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2- C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; R ² is hydrogen, -C(=O)R ^a , -C(=O)OR ^b , -C(=O)NR ^c R ^d , -CH2OC(=O)OR ^b , -CH(CH3)OC(=O)OR ^b , - C(CH ₃ ) ₂ OC(=O)OR ^b , -CH ₂ OC(=O)R ^a , -CH(CH ₃ )OC(=O)R ^a , -C(CH ₃ ) ₂ OC(=O)R ^a , - CH ₂ OP(=O)(OR ^b ) ₂ , -P(=O)(OR ^b ) ₂ , -P(=O)(OR ^b )(NR ^b ), C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ - C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, or heterocycloalkyl; R ³ is -S(=O)R ^a , -S(=O)2R ^a , -S(=O)2NR ^c R ^d , -C(=O)R ^a , -C(=O)OR ^b , -C(=O)NR ^c R ^d , C1-C6alkyl, C1- C ₆ haloalkyl, C ₁ -C ₆ hydroxyalkyl, C ₁ -C ₆ aminoalkyl, C ₁ -C ₆ heteroalkyl, C ₂ -C ₆ alkenyl, C ₂ -C ₆ alkynyl, cycloalkyl, or heterocycloalkyl; Ring B is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; each R ⁵ is independently halogen, -CN, -NO ₂ , -OH, -OR ^a , -OC(=O)R ^a , -OC(=O)OR ^b , -OC(=O)NR ^c R ^d , - SF5, -SH, -SR ^a , -S(=O)R ^a , -S(=O)2R ^a , -S(=O)2NR ^c R ^d , -S(=O)(=NR ^b )R ^b , -NR ^c R ^d , -NR ^b C(=O)NR ^c R ^d , - NR ^b C(=O)R ^a , -NR ^b C(=O)OR ^b , -NR ^b S(=O)2R ^a , -N=S(=O)(R ^b )2, -C(=O)R ^a , -C(=O)OR ^b , -C(=O)O-C1- C6alkylene-OR ^b , -C(=O)NR ^c R ^d , -C(=O)NR ^c -C1-C6alkylene-OR ^b , -P(=O)(R ^b )2, C1-C6alkyl, C1- C ₆ haloalkyl, C ₁ -C ₆ hydroxyalkyl, C ₁ -C ₆ aminoalkyl, C ₁ -C ₆ heteroalkyl, C ₂ -C ₆ alkenyl, C ₂ -C ₆ alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^5a ; or two R ⁵ on the same atom are taken together to form an oxo; each R ^5a is independently halogen, -CN, -NO2, -OH, -OR ^a , -OC(=O)R ^a , -OC(=O)OR ^b , -OC(=O)NR ^c R ^d , - SF5, -SH, -SR ^a , -S(=O)R ^a , -S(=O)2R ^a , -S(=O)2NR ^c R ^d , -S(=O)(=NR ^b )R ^b , -NR ^c R ^d , -NR ^b C(=O)NR ^c R ^d , - NR ^b C(=O)R ^a , -NR ^b C(=O)OR ^b , -NR ^b S(=O) ₂ R ^a , -N=S(=O)(R ^b ) ₂ , -C(=O)R ^a , -C(=O)OR ^b , - C(=O)NR ^c R ^d , -P(=O)(R ^b )2, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1- C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or two R ^5a on the same atom are taken together to form an oxo; m is 0, 1, 2, 3, or 4; R ⁶ is hydrogen, -S(=O)R ^a , -S(=O) ₂ R ^a , -S(=O) ₂ NR ^c R ^d , -C(=O)R ^a , -C(=O)OR ^b , -C(=O)NR ^c R ^d , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ hydroxyalkyl, C ₁ -C ₆ aminoalkyl, C ₁ -C ₆ heteroalkyl, C ₂ -C ₆ alkenyl, C ₂ -C ₆ alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6alkylene(cycloalkyl), C1- C6alkylene(heterocycloalkyl), C1-C6alkylene(aryl), or C1-C6alkylene(heteroaryl); wherein the alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^6a ; each R ^6a is independently halogen, -CN, -NO2, -OH, -OR ^a , -OC(=O)R ^a , -OC(=O)OR ^b , -OC(=O)NR ^c R ^d , - SF5, -SH, -SR ^a , -S(=O)R ^a , -S(=O)2R ^a , -S(=O)2NR ^c R ^d , -S(=O)(=NR ^b )R ^b , -NR ^c R ^d , -NR ^b C(=O)NR ^c R ^d , - NR ^b C(=O)R ^a , -NR ^b C(=O)OR ^b , -NR ^b S(=O) ₂ R ^a , -N=S(=O)(R ^b ) ₂ , -C(=O)R ^a , -C(=O)OR ^b , - C(=O)NR ^c R ^d , -P(=O)(R ^b )2, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1- C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or two R ^6a on the same atom are taken together to form an oxo; R ⁷ is hydrogen, -S(=O)R ^a , -S(=O) ₂ R ^a , -S(=O) ₂ NR ^c R ^d , -C(=O)R ^a , -C(=O)OR ^b , -C(=O)NR ^c R ^d , C ₁ -C ₆ alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; ^{each Ra is independently C} 1 ^-C 6 ^{alkyl, C} 1 ^-C 6 ^{haloalkyl, C} 1 ^-C 6 ^{hydroxyalkyl, C} 1 ^-C 6 ^{aminoalkyl, C} 1- C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1- C6alkylene(cycloalkyl), C1-C6alkylene(heterocycloalkyl), C1-C6alkylene(aryl), or C1- C ₆ alkylene(heteroaryl); wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each R ^b is independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1- C ₆ alkylene(cycloalkyl), C ₁ -C ₆ alkylene(heterocycloalkyl), C ₁ -C ₆ alkylene(aryl), or C ₁ - C6alkylene(heteroaryl); wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; R ^c and R ^d are each independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ hydroxyalkyl, C ₁ - C6 ^{aminoalkyl, C} 1 ^-C 6 ^{heteroalkyl, C} 2 ^-C 6 ^{alkenyl, C} 2 ^-C 6 ^{alkynyl, cycloalkyl, heterocycloalkyl, aryl,} heteroaryl, C1-C6alkylene(cycloalkyl), C1-C6alkylene(heterocycloalkyl), C1-C6alkylene(aryl), or C1- C6alkylene(heteroaryl); wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or R ^c and R ^d are taken together with the atom to which they are attached to form a heterocycloalkyl independently optionally substituted with one or more R; and each R is independently halogen, -CN, -OH, -SF ₅ , -SH, -S(=O)C ₁ -C ₃ alkyl, -S(=O) ₂ C ₁ -C ₃ alkyl, - S(=O) ₂ NH ₂ , -S(=O) ₂ NHC ₁ -C ₃ alkyl, -S(=O) ₂ N(C ₁ -C ₃ alkyl) ₂ , -S(=O)(=NC ₁ -C ₃ alkyl)(C ₁ -C ₃ alkyl), - NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, -N=S(=O)(C1-C3alkyl)2, -C(=O)C1-C3alkyl, -C(=O)OH, - C(=O)OC1-C3alkyl, -C(=O)NH2, -C(=O)NHC1-C3alkyl, -C(=O)N(C1-C3alkyl)2, -P(=O)(C1-C3alkyl)2, C ₁ -C ₃ alkyl, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkyl, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ hydroxyalkyl, C ₁ -C ₃ aminoalkyl, C1-C3heteroalkyl, or C3-C6cycloalkyl; or two R on the same atom form an oxo. [00112] In some embodiments of a compound of Formula (II), the compound is of Formula (IIa): Formula (IIa). [00113] In some embodiments of a compound of Formula (II) or (IIa), Ring B is phenyl or heteroaryl. In some embodiments of a compound of Formula (II) or (IIa), Ring B is phenyl. In some embodiments of a compound of Formula (II) or (IIa), Ring B is 5- or 6-membered heteroaryl. In some embodiments of a compound of Formula (II) or (IIa), Ring B is 6-membered heteroaryl. [00114] In some embodiments of a compound of Formula (II) or (IIa), Ring B is cycloalkyl or heterocycloalkyl. [00115] In some embodiments of a compound of Formula (II) or (IIa), Ring B is monocyclic cycloalkyl or monocyclic heterocycloalkyl. In some embodiments of a compound of Formula (II) or (IIa), Ring B is monocyclic heterocycloalkyl. In some embodiments of a compound of Formula (II) or (IIa), Ring B is 4- to 6-membered heterocycloalkyl comprising one or two heteroatoms selected from the group consisting of O, S, and N. [00116] In some embodiments of a compound of Formula (II) or (IIa), Ring B is a bicyclic heteroaryl or bicyclic heterocycloalkyl. [00117] In some embodiments of a compound of Formula (II) or (IIa), Ring B is a 8- to 12-membered bicyclic heteroaryl or a 8- to 12-membered bicyclic heterocycloalkyl; wherein the heteroaryl or heterocycloalkyl comprises one to four heteroatoms selected from the group consisting of O, S, and N. [00118] In some embodiments of a compound of Formula (II) or (IIa), Ring B is a 8- to 12-membered bicyclic heteroaryl or a 8- to 12-membered bicyclic heterocycloalkyl; wherein the heteroaryl or heterocycloalkyl comprises one to three heteroatoms selected from the group consisting of O, S, and N. In some embodiments of a compound of Formula (II) or (IIa), Ring B is a 8- to 12-membered bicyclic heteroaryl or a 8- to 12-membered bicyclic heterocycloalkyl; wherein the heteroaryl or heterocycloalkyl comprises one to two heteroatoms selected from the group consisting of O, S, and N. In some embodiments of a compound of Formula (II) or (IIa), Ring B is a 8- to 12-membered bicyclic heteroaryl or a 8- to 12-membered bicyclic heterocycloalkyl; wherein the heteroaryl or heterocycloalkyl comprises one to two heteroatoms selected from the group consisting of O and N. [00119] In some embodiments of a compound of Formula (II) or (IIa), Ring B is a bicyclic heteroaryl. [00120] In some embodiments of a compound of Formula (II) or (IIa), Ring B is a 8- to 12-membered bicyclic heteroaryl comprising one to four heteroatoms selected from the group consisting of O, S, and N. [00121] In some embodiments of a compound of Formula (II) or (IIa), Ring B is a 8- to 12-membered bicyclic heteroaryl comprising one to three heteroatoms selected from the group consisting of O, S, and N. [00122] In some embodiments of a compound of Formula (II) or (IIa), Ring B is a 8- to 12-membered bicyclic heteroaryl comprising one to two heteroatoms selected from the group consisting of O and N. [00123] In some embodiments of a compound of Formula (II) or (IIa), Ring B is benzimidazole, benzoxazole, or benzothiazole. In some embodiments of a compound of Formula (II) or (IIa), Ring B is benzimidazole. [00124] In some embodiments of a compound of Formula (II) or (IIa), Ring B is a bicyclic heterocycloalkyl. [00125] In some embodiments of a compound of Formula (II) or (IIa), Ring B is a 8- to 12-membered bicyclic heterocycloalkyl comprising one to four heteroatoms selected from the group consisting of O, S, and N. [00126] In some embodiments of a compound of Formula (II) or (IIa), Ring B is a 8- to 12-membered bicyclic heterocycloalkyl comprising one to three heteroatoms selected from the group consisting of O, S, and N. [00127] In some embodiments of a compound of Formula (II) or (IIa), Ring B is a 8- to 12-membered bicyclic heterocycloalkyl comprising one to two heteroatoms selected from the group consisting of O and N. [00128] In some embodiments of a compound of Formula (II) or (IIa), Ring B is isoindolinyl, tetrahydroisoquinolinyl, or tetrahydrobenzoazepinyl. In some embodiments of a compound of Formula (II) or (IIa), Ring B is tetrahydroisoquinolinyl. [00129] In some embodiments of a compound of Formula (II) or (IIa), each R ⁵ is independently halogen, -CN, -NO ₂ , -OH, -OR ^a , -OC(=O)R ^a , -OC(=O)OR ^b , -OC(=O)NR ^c R ^d , -SF ₅ , -SH, -SR ^a , -S(=O)R ^a , -S(=O) ₂ R ^a , -S(=O) ₂ NR ^c R ^d , -S(=O)(=NR ^b )R ^b , -NR ^c R ^d , -NR ^b C(=O)NR ^c R ^d , -NR ^b C(=O)R ^a , -NR ^b C(=O)OR ^b , -NR ^b S(=O)2R ^a , -N=S(=O)(R ^b )2, -C(=O)R ^a , -C(=O)OR ^b , -C(=O)NR ^c R ^d , -P(=O)(R ^b )2, C1-C6alkyl, C1- C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^5a . [00130] In some embodiments of a compound of Formula (II) or (IIa), each R ⁵ is independently halogen, -CN, -OH, -OR ^a , -NR ^c R ^d , -NR ^b C(=O)NR ^c R ^d , -NR ^b C(=O)R ^a , -NR ^b C(=O)OR ^b , -C(=O)R ^a , - C(=O)OR ^b , -C(=O)NR ^c R ^d , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ hydroxyalkyl, C ₁ -C ₆ aminoalkyl, C ₁ - C6heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^5a . [00131] In some embodiments of a compound of Formula (II) or (IIa), each R ⁵ is independently halogen, -NR ^c R ^d , -NR ^b C(=O)NR ^c R ^d , -NR ^b C(=O)R ^a , -NR ^b C(=O)OR ^b , -C(=O)R ^a , -C(=O)OR ^b , - C(=O)NR ^c R ^d , C ₁ -C ₆ alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^5a . [00132] In some embodiments of a compound of Formula (II) or (IIa), each R ⁵ is independently - NR ^b C(=O)NR ^c R ^d , -NR ^b C(=O)R ^a , -NR ^b C(=O)OR ^b , -C(=O)OR ^b , -C(=O)NR ^c R ^d , C1-C6alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^5a . [00133] In some embodiments of a compound of Formula (II) or (IIa), each R ⁵ is independently - C(=O)OR ^b , -C(=O)NR ^c R ^d , C1-C6alkyl, cycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^5a . [00134] In some embodiments of a compound of Formula (II) or (IIa), each R ⁵ is independently - C(=O)OR ^b , -C(=O)NR ^c R ^d , or aryl; wherein each aryl is independently optionally substituted with one or more R ^5a . _[00135] In some embodiments of a compound of Formula (II) or (IIa), each R ⁵ is independently C ₁ - C6alkyl or aryl; wherein each alkyl and aryl is independently optionally substituted with one or more R ^5a . [00136] In some embodiments of a compound of Formula (II) or (IIa), each R ⁵ is independently halogen, -CN, -OH, -OR ^a , -NR ^c R ^d , -C(=O)R ^a , -C(=O)OR ^b , -C(=O)NR ^c R ^d , C1-C6alkyl, C1-C6haloalkyl, C ₁ -C ₆ hydroxyalkyl, C ₁ -C ₆ aminoalkyl, C ₁ -C ₆ heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^5a . In some embodiments of a compound of Formula (II) or (IIa), each R ⁵ is independently halogen, -OH, -OR ^a , -NR ^c R ^d , C1-C6alkyl, C1-C6haloalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^5a . In some embodiments of a compound of Formula (II) or (IIa), each R ⁵ is independently halogen, C1-C6alkyl, C1-C6haloalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently ^{optionally substituted with one or more R5a. In some embodiments of a compound of Formula (II) or} (IIa), each R ⁵ is independently cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^5a . In some embodiments of a compound of Formula (II) or (IIa), each R ⁵ is independently cycloalkyl, aryl, or heteroaryl; wherein each cycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^5a . In some embodiments of a compound of Formula (II) or (IIa), each R ⁵ is independently cycloalkyl or heterocycloalkyl; wherein each cycloalkyl and heterocycloalkyl is independently optionally substituted with one or more R ^5a . In some embodiments of a compound of Formula (II) or (IIa), each R ⁵ is independently cycloalkyl or heterocycloalkyl. In some embodiments of a compound of Formula (II) or (IIa), each R ⁵ is independently aryl or heteroaryl; wherein each aryl and heteroaryl is independently optionally substituted with one or more R ^5a . In some embodiments of a compound of Formula (II) or (IIa), each R ⁵ is independently aryl or heteroaryl. [00137] In some embodiments of a compound of Formula (II) or (IIa), each R ^5a is independently halogen, -CN, -OH, -OR ^a , -NR ^c R ^d , -C(=O)R ^a , -C(=O)OR ^b , -C(=O)NR ^c R ^d , C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, cycloalkyl, or heterocycloalkyl; wherein each alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (II) or (IIa), each R ^5a is independently halogen, -CN, -OH, -OR ^a , -NR ^c R ^d , C1-C6alkyl, C1-C6haloalkyl, cycloalkyl, or heterocycloalkyl; wherein each alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (II) or (IIa), each R ^5a is independently halogen, -CN, -OH, - OR ^a , -NR ^c R ^d , C1-C6alkyl, or C1-C6haloalkyl; wherein each alkyl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (II) or (IIa), each R ^5a is independently halogen, -CN, -OH, -OR ^a , -NR ^c R ^d , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, or heterocycloalkyl. In some embodiments of a compound of Formula (II) or (IIa), each R ^5a is independently halogen, -CN, -OH, -OR ^a , -NR ^c R ^d , C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (II) or (IIa), each R ^5a is independently halogen, C ₁ -C ₆ alkyl, or C ₁ -C ₆ haloalkyl. In some ^{embodiments of a compound of Formula (II) or (IIa), each R5a is independently halogen or C} 1 ^-C 6 ^alkyl. [00138] In some embodiments of a compound of Formula (II) or (IIa), each R ^5a is independently halogen, -CN, -OH, -OR ^a , -NR ^c R ^d , -C(=O)R ^a , -C(=O)OR ^b , -C(=O)NR ^c R ^d , C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, or C1-C6heteroalkyl. [00139] In some embodiments of a compound of Formula (II) or (IIa), each R ^5a is independently halogen, -CN, -OH, -OR ^a , -NR ^c R ^d , -C(=O)OR ^b , -C(=O)NR ^c R ^d , or C ₁ -C ₆ alkyl. _[00140] In some embodiments of a compound of Formula (II) or (IIa), each R ^5a is independently halogen, -CN, -OR ^a , -C(=O)OR ^b , -C(=O)NR ^c R ^d , or C1-C6alkyl. [00141] In some embodiments of a compound of Formula (II) or (IIa), each R ^5a is independently - C(=O)OR ^b or -C(=O)NR ^c R ^d . [00142] In some embodiments of a compound of Formula (II) or (IIa), each R ^5a is independently halogen, -CN, -OR ^a , or C ₁ -C ₆ alkyl. [00143] In some embodiments of a compound of Formula (II) or (IIa), each R ^5a is independently halogen, -OR ^a , or C1-C6alkyl. [00144] In some embodiments of a compound of Formula (II) or (IIa), each R ^5a is independently halogen. [00146] In some embodiments of a compound of Formula (II) or (IIa), m is 0, 1, 2, or 3. In some embodiments of a compound of Formula (II) or (IIa), m is 0, 1, or 2. In some embodiments of a compound of Formula (II) or (IIa), m is 1 or 2. In some embodiments of a compound of Formula (II) or (IIa), m is 0 or 1. In some embodiments of a compound of Formula (II) or (IIa), m is 0. In some embodiments of a compound of Formula (II) or (IIa), m is 1. In some embodiments of a compound of Formula (II) or (IIa), m is 2. In some embodiments of a compound of Formula (II) or (IIa), m is 3. [00147] In some embodiments of a compound of Formula (II) or (IIa), the compound is of Formula (IIa-1): Formula (IIa-1); wherein: each R ¹⁰ is independently halogen, -CN, -NO2, -OH, -OR ^a , -OC(=O)R ^a , -OC(=O)OR ^b , -OC(=O)NR ^c R ^d , - SF5, -SH, -SR ^a , -S(=O)R ^a , -S(=O)2R ^a , -S(=O)2NR ^c R ^d , -S(=O)(=NR ^b )R ^b , -NR ^c R ^d , -NR ^b C(=O)NR ^c R ^d , - NR ^b C(=O)R ^a , -NR ^b C(=O)OR ^b , -NR ^b S(=O) ₂ R ^a , -N=S(=O)(R ^b ) ₂ , -C(=O)R ^a , -C(=O)OR ^b , - C ^{(=O)NRcRd, -P(=O)(Rb)} 2 ^{, C} 1 ^-C 6 ^{alkyl, C} 1 ^-C 6 ^{haloalkyl, C} 1 ^-C 6 ^{hydroxyalkyl, C} 1 ^-C 6 ^{aminoalkyl, C} 1- C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^10a ; each R ^10a is independently halogen, -CN, -NO2, -OH, -OR ^a , -OC(=O)R ^a , -OC(=O)OR ^b , -OC(=O)NR ^c R ^d , - SF5, -SH, -SR ^a , -S(=O)R ^a , -S(=O)2R ^a , -S(=O)2NR ^c R ^d , -S(=O)(=NR ^b )R ^b , -NR ^c R ^d , -NR ^b C(=O)NR ^c R ^d , - NR ^b C(=O)R ^a , -NR ^b C(=O)OR ^b , -NR ^b S(=O) ₂ R ^a , -N=S(=O)(R ^b ) ₂ , -C(=O)R ^a , -C(=O)OR ^b , - C(=O)NR ^c R ^d , -P(=O)(R ^b ) ₂ , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ hydroxyalkyl, C ₁ -C ₆ aminoalkyl, C ₁ - C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or two R ^10a on the same atom are taken together to form an oxo; s is 0, 1, or 2; each R ¹¹ is independently halogen, -CN, -NO2, -OH, -OR ^a , -OC(=O)R ^a , -OC(=O)OR ^b , -OC(=O)NR ^c R ^d , - SF ₅ , -SH, -SR ^a , -S(=O)R ^a , -S(=O) ₂ R ^a , -S(=O) ₂ NR ^c R ^d , -S(=O)(=NR ^b )R ^b , -NR ^c R ^d , -NR ^b C(=O)NR ^c R ^d , - NR ^b C(=O)R ^a , -NR ^b C(=O)OR ^b , -NR ^b S(=O)2R ^a , -N=S(=O)(R ^b )2, -C(=O)R ^a , -C(=O)OR ^b , -C(=O)O-C1- C6alkylene-OR ^b , -C(=O)NR ^c R ^d , -C(=O)NR ^c -C1-C6alkylene-OR ^b , -P(=O)(R ^b )2, C1-C6alkyl, C1- C ₆ haloalkyl, C ₁ -C ₆ hydroxyalkyl, C ₁ -C ₆ aminoalkyl, C ₁ -C ₆ heteroalkyl, C ₂ -C ₆ alkenyl, C ₂ -C ₆ alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^11a ; each R ^11a is independently halogen, -CN, -NO2, -OH, -OR ^a , -OC(=O)R ^a , -OC(=O)OR ^b , -OC(=O)NR ^c R ^d , - SF ₅ , -SH, -SR ^a , -S(=O)R ^a , -S(=O) ₂ R ^a , -S(=O) ₂ NR ^c R ^d , -S(=O)(=NR ^b )R ^b , -NR ^c R ^d , -NR ^b C(=O)NR ^c R ^d , - NR ^b C(=O)R ^a , -NR ^b C(=O)OR ^b , -NR ^b S(=O)2R ^a , -N=S(=O)(R ^b )2, -C(=O)R ^a , -C(=O)OR ^b , - C(=O)NR ^c R ^d , -P(=O)(R ^b )2, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1- C ₆ heteroalkyl, C ₂ -C ₆ alkenyl, C ₂ -C ₆ alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; and t is 0, 1, or 2. [00148] In some embodiments of a compound of Formula (IIa-1), each R ¹⁰ is independently halogen, - CN, -OH, -OR ^a , -NR ^c R ^d , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ hydroxyalkyl, C ₁ -C ₆ aminoalkyl, C ₁ - C6heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^10a . [00149] In some embodiments of a compound of Formula (IIa-1), each R ¹⁰ is independently halogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^10a . [00150] In some embodiments of a compound of Formula (IIa-1), each R ¹⁰ is independently C1-C6alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^10a . [00151] In some embodiments of a compound of Formula (IIa-1), each R ¹⁰ is independently cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^10a . [00152] In some embodiments of a compound of Formula (IIa-1), each R ¹⁰ is independently aryl or heteroaryl; wherein each aryl and heteroaryl is independently optionally substituted with one or more R ^10a . [00153] In some embodiments of a compound of Formula (Ib), each R ¹⁰ is independently phenyl independently optionally substituted with one or more R ^10a . [00154] In some embodiments of a compound of Formula (IIa-1), each R ^10a is independently halogen, - CN, -OH, -OR ^a , -NR ^c R ^d , -C(=O)R ^a , -C(=O)OR ^b , -C(=O)NR ^c R ^d , C1-C6alkyl, C1-C6haloalkyl, C1- C ₆ hydroxyalkyl, C ₁ -C ₆ aminoalkyl, or C ₁ -C ₆ heteroalkyl. [00155] In some embodiments of a compound of Formula (IIa-1), each R ^10a is independently halogen, - CN, -OH, -OR ^a , -NR ^c R ^d , -C(=O)R ^a , -C(=O)OR ^b , -C(=O)NR ^c R ^d , or C1-C6alkyl. [00156] In some embodiments of a compound of Formula (IIa-1), each R ^10a is independently halogen, - CN, -OH, -OR ^a , -NR ^c R ^d , -C(=O)OR ^b , -C(=O)NR ^c R ^d , or C1-C6alkyl. [00157] In some embodiments of a compound of Formula (IIa-1), each R ^10a is independently halogen, - CN, -OR ^a , -C(=O)OR ^b , or C1-C6alkyl. [00158] In some embodiments of a compound of Formula (IIa-1), each R ^10a is independently halogen. _[00159] In some embodiments of a compound of Formula (IIa-1), each R ¹⁰ is independently , , , , . In some embodiments of a compound of Formula (IIa- , , , . In some embodiments of a compound of Formula (IIa- 1), each R ¹⁰ is independently . In some embodiments of a compound of Formula (IIa-1), each R ¹⁰ is independently . In some embodiments of a compound of Formula (IIa-1), each R ¹⁰ is independently . In some embodiments of a compound of Formula (IIa-1), each R ¹⁰ is independently . [00160] In some embodiments of a compound of Formula (IIa-1), s is 0 or 1. In some embodiments of a compound of Formula (IIa-1), s is 1 or 2. In some embodiments of a compound of Formula (IIa-1), s is 0. In some embodiments of a compound of Formula (IIa-1), s is 1. In some embodiments of a compound of Formula (IIa-1), s is 2. [00161] In some embodiments of a compound of Formula (IIa-1), each R ¹¹ is independently halogen, - CN, -OH, -OR ^a , -NR ^c R ^d , -NR ^b C(=O)NR ^c R ^d , -NR ^b C(=O)R ^a , -NR ^b C(=O)OR ^b , -C(=O)R ^a , -C(=O)OR ^b , - C(=O)NR ^c R ^d , -C(=O)NR ^c -C1-C6alkylene-OR ^b , C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1- C ₆ aminoalkyl, or C ₁ -C ₆ heteroalkyl. [00162] In some embodiments of a compound of Formula (IIa-1), each R ¹¹ is independently halogen, - CN, -OH, -OR ^a , -NR ^c R ^d , -NR ^b C(=O)NR ^c R ^d , -NR ^b C(=O)R ^a , -NR ^b C(=O)OR ^b , -C(=O)R ^a , -C(=O)OR ^b , - C(=O)NR ^c R ^d , C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, or C1-C6heteroalkyl. [00163] In some embodiments of a compound of Formula (IIa-1), each R ¹¹ is independently halogen, - NR ^c R ^d , -NR ^b C(=O)NR ^c R ^d , -NR ^b C(=O)R ^a , -NR ^b C(=O)OR ^b , -C(=O)OR ^b , or -C(=O)NR ^c R ^d . [00164] In some embodiments of a compound of Formula (IIa-1), each R ¹¹ is independently - NR ^b C(=O)NR ^c R ^d , -NR ^b C(=O)R ^a , -NR ^b C(=O)OR ^b , -C(=O)OR ^b , or -C(=O)NR ^c R ^d . [00165] ^{In some embodiments of a compound of Formula (IIa-1), each R11 is independently -} C(=O)OR ^b or -C(=O)NR ^c R ^d . [00166] In some embodiments of a compound of Formula (IIa-1), each R ¹¹ is independently - C(=O)OR ^b . [00167] In some embodiments of a compound of Formula (IIa-1), each R ¹¹ is independently - C(=O)NR ^c R ^d . [00168] In some embodiments of a compound of Formula (IIa-1), t is 0 or 1. In some embodiments of a compound of Formula (IIa-1), t is 1 or 2. In some embodiments of a compound of Formula (IIa-1), t is 0. In some embodiments of a compound of Formula (IIa-1), t is 1. In some embodiments of a compound of Formula (IIa-1), t is 2. [00169] In some embodiments of a compound of Formula (IIa-1), each R ¹¹ is independently , , or . In some embodiments of a compound of Formula (IIa-1), each R ¹¹ is . In some embodiments of a compound of Formula (IIa-1), each R ¹¹ is independently . In some embodiments of a compound of Formula (IIa-1), each R ¹¹ is independently . In some embodiments of a compound of Formula (IIa-1), each R ¹¹ is independently . In some embodiments of a compound of Formula (IIa-1), each R ¹¹ is independently . In some embodiments of a compound of Formula (IIa-1), each R ¹¹ is independently of a compound of Formula (IIa-1), each R ¹¹ is independently . In some embodiments of a compound of Formula (IIa-1), each R ¹¹ is independently . In some embodiments of a compound of Formula (IIa-1), each R ¹¹ is independently . In some embodiments of a compound of Formula (IIa-1), each R ¹¹ is independently . In some embodiments of a compound of Formula (IIa-1), each R ¹¹ is independently . In some embodiments of a compound of Formula (IIa-1), each R ¹¹ is independently . [00170] In some embodiments of a compound of Formula (IIa-1), the compound has the following formula: some embodiments of a compound of Formula (IIa-1), some embodiments of a compound of Formula (IIa-1), the compound has the following formula: some embodiments of a compound of Formula (IIa-1), the some embodiments of a compound of Formula (IIa-1), the compound has the following formula:

[00171] In some embodiments of a compound of Formula (II), the compound is of Formula (IIb): Formula (IIb). [00172] In some embodiments of a compound of Formula (II) or (IIb), R ⁶ is cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6alkylene(cycloalkyl), C1-C6alkylene(heterocycloalkyl), C1- C6alkylene(aryl), or C1-C6alkylene(heteroaryl); wherein the alkylene, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^6a . [00173] In some embodiments of a compound of Formula (II) or (IIb), R ⁶ is C1-C6alkylene(cycloalkyl), C1-C6alkylene(heterocycloalkyl), C1-C6alkylene(aryl), or C1-C6alkylene(heteroaryl); wherein the alkylene, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^6a . _[00174] In some embodiments of a compound of Formula (II) or (IIb), R ⁶ is C ₁ -C ₆ alkylene(cycloalkyl) or C1-C6alkylene(aryl); wherein the alkylene, cycloalkyl, and aryl is independently optionally substituted with one or more R ^6a . [00175] In some embodiments of a compound of Formula (II) or (IIb), R ⁶ is C1-C6alkylene(aryl); wherein the alkylene and aryl is independently optionally substituted with one or more R ^6a . [00176] In some embodiments of a compound of Formula (II) or (IIb), R ⁶ is C ₁ -C ₆ alkylene(cycloalkyl); wherein the alkylene and cycloalkyl is independently optionally substituted with one or more R ^6a . [00177] In some embodiments of a compound of Formula (II) or (IIb), each R ^6a is independently halogen, -CN, -OH, -OR ^a , -NR ^c R ^d , -NR ^b S(=O)2R ^a , -C(=O)R ^a , -C(=O)OR ^b , -C(=O)NR ^c R ^d , C1-C6alkyl, C1- C ₆ haloalkyl, C ₁ -C ₆ hydroxyalkyl, C ₁ -C ₆ aminoalkyl, C ₁ -C ₆ heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (II) or (IIb), each R ^6a is independently halogen, -CN, -OH, -OR ^a , -NR ^c R ^d , -NR ^b S(=O)2R ^a , -C(=O)R ^a , -C(=O)OR ^b , - C(=O)NR ^c R ^d , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (II) or (IIb), each R ^6a is independently halogen, -CN, -NR ^b S(=O) ₂ R ^a , -C(=O)OR ^b , -C(=O)NR ^c R ^d , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (II) or (IIb), each R ^6a is independently halogen, -CN, -NR ^b S(=O)2R ^a , -C(=O)OR ^b , - C(=O)NR ^c R ^d , cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (II) or (IIb), each R ^6a is independently halogen, -CN, - NR ^b S(=O)2R ^a , -C(=O)OR ^b , -C(=O)NR ^c R ^d , cycloalkyl, aryl, or heteroaryl; wherein each cycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (II) or (IIb), each R ^6a is independently halogen, -CN, -NR ^b S(=O)2R ^a , -C(=O)OR ^b , - C(=O)NR ^c R ^d , or cycloalkyl; wherein each cycloalkyl is independently optionally substituted with one or more R. [00178] In some embodiments of a compound of Formula (II) or (IIb), the compound is of Formula (IIc): wherein: Ring C is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; each R ⁸ is independently halogen, -CN, -OH, -SF ₅ , -SH, -S(=O)C ₁ -C ₃ alkyl, -S(=O) ₂ C ₁ -C ₃ alkyl, - S(=O)2NH2, -S(=O)2NHC1-C3alkyl, -S(=O)2N(C1-C3alkyl)2, -S(=O)(=NC1-C3alkyl)(C1-C3alkyl), - NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, -N=S(=O)(C1-C3alkyl)2, -C(=O)C1-C3alkyl, -C(=O)OH, - C(=O)OC1-C3alkyl, -C(=O)NH2, -C(=O)NHC1-C3alkyl, -C(=O)N(C1-C3alkyl)2, -P(=O)(C1-C3alkyl)2, C ₁ -C ₃ alkyl, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkyl, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ hydroxyalkyl, C ₁ -C ₃ aminoalkyl, C1-C3heteroalkyl, or C3-C6cycloalkyl; p is 0, 1, 2, 3, or 4; Ring D is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; each R ⁹ is independently halogen, -CN, -NO2, -OH, -OR ^a , -OC(=O)R ^a , -OC(=O)OR ^b , -OC(=O)NR ^c R ^d , - SF5, -SH, -SR ^a , -S(=O)R ^a , -S(=O)2R ^a , -S(=O)2NR ^c R ^d , -S(=O)(=NR ^b )R ^b , -NR ^c R ^d , -NR ^b C(=O)NR ^c R ^d , - NR ^b C(=O)R ^a , -NR ^b C(=O)OR ^b , -NR ^b S(=O)2R ^a , -N=S(=O)(R ^b )2, -C(=O)R ^a , -C(=O)OR ^b , - C(=O)NR ^c R ^d , -P(=O)(R ^b ) ₂ , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ hydroxyalkyl, C ₁ -C ₆ aminoalkyl, C ₁ - C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; ^{or two R9 on the same atom are taken together to form an oxo;} q is 0, 1, 2, 3, or 4. [00179] In some embodiments of a compound of Formula (IIc), Ring C is cycloalkyl or heterocycloalkyl. In some embodiments of a compound of Formula (IIc), Ring C is aryl or heteroaryl. In some embodiments of a compound of Formula (IIc), Ring C is cycloalkyl or aryl. In some embodiments of a compound of Formula (IIc), Ring C is cycloalkyl. In some embodiments of a compound of Formula (IIc), Ring C is aryl. In some embodiments of a compound of Formula (IIc), Ring C is phenyl. [00180] In some embodiments of a compound of Formula (IIc), each R ⁸ is independently halogen, -CN, -OH, -NH ₂ , -NHC ₁ -C ₃ alkyl, -N(C ₁ -C ₃ alkyl) ₂ , -C(=O)C ₁ -C ₃ alkyl, -C(=O)OH, -C(=O)OC ₁ -C ₃ alkyl, - C(=O)NH ₂ , -C(=O)NHC ₁ -C ₃ alkyl, -C(=O)N(C ₁ -C ₃ alkyl) ₂ , C ₁ -C ₃ alkyl, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkyl, C ₁ - C3haloalkoxy, C1-C3hydroxyalkyl, C1-C3aminoalkyl, C1-C3heteroalkyl, or C3-C6cycloalkyl. In some embodiments of a compound of Formula (IIc), each R ⁸ is independently halogen, -CN, -OH, -NH2, - NHC ₁ -C ₃ alkyl, -N(C ₁ -C ₃ alkyl) ₂ , C ₁ -C ₃ alkyl, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkyl, C ₁ -C ₃ haloalkoxy, C ₁ - C3hydroxyalkyl, C1-C3aminoalkyl, C1-C3heteroalkyl, or C3-C6cycloalkyl. In some embodiments of a compound of Formula (IIc), each R ⁸ is independently halogen, -CN, -OH, -NH2, -NHC1-C3alkyl, -N(C1- C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, or C1-C3haloalkoxy. In some embodiments of a compound of Formula (IIc), each R ⁸ is independently halogen, -CN, -OH, -NH ₂ , C ₁ -C ₃ alkyl, or C ₁ - C3haloalkyl. In some embodiments of a compound of Formula (IIc), each R ⁸ is independently halogen, C1-C3alkyl, or C1-C3haloalkyl. In some embodiments of a compound of Formula (IIc), each R ⁸ is independently halogen or C ₁ -C ₃ alkyl. [00181] In some embodiments of a compound of Formula (IIc), p is 0, 1, or 2. In some embodiments of a compound of Formula (IIc), p is 0 or 1. In some embodiments of a compound of Formula (IIc), p is 1 or 2. In some embodiments of a compound of Formula (IIc), p is 0. In some embodiments of a compound of Formula (IIc), p is 1. In some embodiments of a compound of Formula (IIc), p is 2. In some embodiments of a compound of Formula (IIc), p is 3. [00182] In some embodiments of a compound of Formula (IIc), Ring D is cycloalkyl or heterocycloalkyl. In some embodiments of a compound of Formula (IIc), Ring D is aryl or heteroaryl. In some embodiments of a compound of Formula (IIc), Ring D is cycloalkyl or aryl. In some embodiments of a compound of Formula (IIc), Ring D is cycloalkyl. In some embodiments of a compound of Formula (IIc), Ring D is aryl. In some embodiments of a compound of Formula (IIc), Ring D is phenyl. [00183] In some embodiments of a compound of Formula (IIc), each R ⁹ is independently halogen, -CN, -OH, -OR ^a , -NR ^c R ^d , -NR ^b S(=O)2R ^a , -C(=O)R ^a , -C(=O)OR ^b , -C(=O)NR ^c R ^d , C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (IIc), each R ⁹ is independently halogen, -CN, -OH, -OR ^a , -NR ^c R ^d , -NR ^b S(=O)2R ^a , -C(=O)R ^a , -C(=O)OR ^b , -C(=O)NR ^c R ^d , C1-C6alkyl, C1-C6haloalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (IIc), each R ⁹ is independently halogen, -CN, - OH, -OR ^a , -NR ^c R ^d , -NR ^b S(=O)2R ^a , -C(=O)R ^a , -C(=O)OR ^b , -C(=O)NR ^c R ^d , C1-C6alkyl, or C1-C6haloalkyl; wherein each alkyl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (IIc), each R ⁹ is independently halogen, -CN, -OH, -OR ^a , -NR ^c R ^d , - NR ^b S(=O)2R ^a , -C(=O)R ^a , -C(=O)OR ^b , or -C(=O)NR ^c R ^d . In some embodiments of a compound of Formula (IIc), each R ⁹ is independently halogen, -CN, -NR ^b S(=O)2R ^a , -C(=O)OR ^b , or -C(=O)NR ^c R ^d . [00184] In some embodiments of a compound of Formula (IIc), q is 0, 1, or 2. In some embodiments of a compound of Formula (IIc), q is 0 or 1. In some embodiments of a compound of Formula (IIc), q is 1 or 2. In some embodiments of a compound of Formula (IIc), q is 0. In some embodiments of a compound of Formula (IIc), q is 1. In some embodiments of a compound of Formula (IIc), q is 2. In some embodiments of a compound of Formula (IIc), q is 3. [00185] In some embodiments of a compound of Formula (IIc), the compound has the following formula: . In some embodiments of a compound of Formula (IIc), the compound has the following formula: . [00186] In some embodiments of a compound of Formula (I), (Ib), (Ic), (II), (IIb), or (IIc), R ⁷ is hydrogen or C ₁ -C ₆ alkyl. In some embodiments of a compound of Formula (I), (Ib), (Ic), (II), (IIb), or (IIc), R ⁷ is C1-C6alkyl. In some embodiments of a compound of Formula (I), (Ib), (Ic), (II), (IIb), or (IIc), R ⁷ is hydrogen. [00187] In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), Ring A is cycloalkyl or heterocycloalkyl. In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), Ring A is cycloalkyl. In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), Ring A is phenyl or a 6-membered heteroaryl. In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), Ring A is a 6-membered heteroaryl. In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), Ring A is phenyl. [00188] In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc),each R ¹ is independently halogen, -CN, -OH, -OR ^a , -NR ^c R ^d , -C(=O)R ^a , -C(=O)OR ^b , - C(=O)NR ^c R ^d , C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), each R ¹ is independently halogen, -CN, -OH, -OR ^a , -NR ^c R ^d , -C(=O)R ^a , -C(=O)OR ^b , -C(=O)NR ^c R ^d , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, or heterocycloalkyl; wherein each alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (I), (Ia), (Ia- 1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), each R ¹ is independently halogen, -CN, -OH, -OR ^a , - NR ^c R ^d , -C(=O)R ^a , -C(=O)OR ^b , -C(=O)NR ^c R ^d , C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ hydroxyalkyl, C ₁ - C6aminoalkyl, C1-C6heteroalkyl, cycloalkyl, or heterocycloalkyl. In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), each R ¹ is independently halogen, - CN, -OH, -OR ^a , -NR ^c R ^d , C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), each R ¹ is independently halogen, C ₁ - C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), each R ¹ is independently halogen or C1-C6alkyl. [00189] In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), n is 0, 1, or 2. In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), n is 1 or 2. In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), n is 0 or 1. In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), n is 0. In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), n is 1. In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), n is 2. In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic) (II), (IIa), (IIa-1), (IIb), or (IIc), n is 3. [00190] In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic) (II), (IIa), (IIa-1), (IIb), or (IIc), X ¹ is -O-. In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), X ¹ is -S-. In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), X ¹ is -NR ^X1 -. [00191] In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc),R ^X1 is hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ hydroxyalkyl, C ₁ -C ₆ aminoalkyl, C ₁ - C ₆ heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein the alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^X1a . In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), R ^X1 is hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, or heterocycloalkyl; wherein the alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R ^X1a . In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), R ^X1 is hydrogen, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), R ^X1 is hydrogen or C ₁ -C ₆ alkyl. [00192] In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), each R ^X1a is independently halogen, -CN, -OH, -OR ^a , -NR ^c R ^d , -C(=O)R ^a , -C(=O)OR ^b , - C(=O)NR ^c R ^d , C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), each R ^X1a is independently halogen, -CN, -OH, -OR ^a , -NR ^c R ^d , C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1- C ₆ aminoalkyl, C ₁ -C ₆ heteroalkyl, cycloalkyl, or heterocycloalkyl; wherein each alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), each R ^X1a is independently halogen, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), each R ^X1a is independently halogen or C ₁ - C6alkyl. [00193] In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), X ² is -N-. In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), X ² is -CR ^X2 -. [00194] In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), R ^X2 is hydrogen, halogen, -CN, -OH, -OR ^a , -NR ^c R ^d , C1-C6alkyl, C1-C6haloalkyl, C1- C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, cycloalkyl, or heterocycloalkyl; wherein the alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), R ^X2 is hydrogen, halogen, -CN, -OH, -OR ^a , -NR ^c R ^d , C1-C6alkyl, C1-C6haloalkyl, cycloalkyl, or heterocycloalkyl; wherein the alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), R ^X2 is hydrogen, halogen, C ₁ -C ₆ alkyl, or C ₁ -C ₆ haloalkyl. In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), R ^X2 is hydrogen, halogen, or C1-C6alkyl. [00195] In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), X ¹ is -O- and X ² is -N-. [00196] In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), X ¹ is -NR ^X1 - and X ² is -N-. [00197] In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), R ² is hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), R ² is hydrogen. [00198] In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), R ² is -C(=O)R ^a , -C(=O)OR ^b , or -C(=O)NR ^c R ^d . In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), R ² is -C(=O)R ^a . In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), R ² is -C(=O)OR ^b . In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), R ² is -C(=O)NR ^c R ^d . In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), R ² is -CH2OC(=O)R ^a , -CH(CH3)OC(=O)R ^a , or -C(CH3)2OC(=O)R ^a . In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), R ² is - CH ₂ OC(=O)OR ^b , -CH(CH ₃ )OC(=O)OR ^b , or -C(CH ₃ ) ₂ OC(=O)OR ^b . In some embodiments of a compound ^{of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), R2 is -CH(CH} 3 ^{)OC(=O)ORb. In} some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), R ² is -CH2OP(=O)(OR ^b )2, -P(=O)(OR ^b )2, or -P(=O)(OR ^b )(NR ^b ). [00199] In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), R ³ is C ₁ -C ₆ alkyl. In some embodiments of a compound of Formula (I), (Ia), (Ia-1), (Ib), (Ic), (II), (IIa), (IIa-1), (IIb), or (IIc), R ³ is methyl. [00200] In some embodiments of a compound of Formula (I), (Ia), (Ia-1), or (Ib), R ³ is hydrogen or C1- C6alkyl. In some embodiments of a compound of Formula (I), (Ia), (Ia-1), or (Ib), R ³ is hydrogen. [00201] In some embodiments of a compound disclosed herein, each R ^a is independently C1-C6alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ hydroxyalkyl, C ₁ -C ₆ aminoalkyl, C ₁ -C ₆ heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R. In some embodiments of a compound disclosed herein, each R ^a is independently C1-C6alkyl, C1-C6haloalkyl, cycloalkyl, or heterocycloalkyl; wherein each alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more R. In some embodiments of a compound disclosed herein, each R ^a is independently C1-C6alkyl, or C1-C6haloalkyl; wherein each alkyl is independently optionally substituted with one or more R. In some embodiments of a compound disclosed herein, each R ^a is independently C1-C6alkyl, C1-C6haloalkyl, cycloalkyl, or heterocycloalkyl. In some embodiments of a compound disclosed herein, each R ^a is independently C1- C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound disclosed herein, each R ^a is independently C1-C6alkyl. [00202] In some embodiments of a compound disclosed herein, each R ^b is independently hydrogen, C1- C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ hydroxyalkyl, C ₁ -C ₆ aminoalkyl, C ₁ -C ₆ heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R. In some embodiments of a compound disclosed herein, each R ^b is independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, cycloalkyl, or heterocycloalkyl; wherein each alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more R. In some embodiments of a compound disclosed herein, each R ^b is independently hydrogen, C1-C6alkyl, or C1-C6haloalkyl; wherein each alkyl is independently optionally substituted with one or more R. In some embodiments of a compound disclosed herein, each R ^b is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, or heterocycloalkyl. In some embodiments of a compound disclosed herein, each R ^b is independently hydrogen, C1-C6alkyl, or C1- C6haloalkyl. In some embodiments of a compound disclosed herein, each R ^b is independently hydrogen or C ₁ -C ₆ alkyl. In some embodiments of a compound disclosed herein, each R ^b is hydrogen. In some embodiments of a compound disclosed herein, each R ^b is independently C ₁ -C ₆ alkyl. _[00203] In some embodiments of a compound disclosed herein, R ^c and R ^d are each independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R. In some embodiments of a compound disclosed herein, R ^c and R ^d are each independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, cycloalkyl, or heterocycloalkyl; wherein each alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more R. In some embodiments of a compound disclosed herein, R ^c and R ^d are each independently hydrogen, C ₁ -C ₆ alkyl, or C ₁ -C ₆ haloalkyl; wherein each alkyl is independently optionally substituted with one or more R. In some embodiments of a compound disclosed herein, R ^c and R ^d are each independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, cycloalkyl, or heterocycloalkyl. In some embodiments of a compound disclosed herein, R ^c and R ^d are each independently hydrogen, C ₁ - C ₆ alkyl, or C ₁ -C ₆ haloalkyl. In some embodiments of a compound disclosed herein, R ^c and R ^d are each independently hydrogen or C1-C6alkyl. In some embodiments of a compound disclosed herein, R ^c and R ^d are each hydrogen. In some embodiments of a compound disclosed herein, R ^c and R ^d are each independently C ₁ -C ₆ alkyl. [00204] In some embodiments of a compound disclosed herein, R ^c and R ^d are taken together with the atom to which they are attached to form a heterocycloalkyl independently optionally substituted with one or more R. [00205] In some embodiments of a compound disclosed herein, each R is independently halogen, -CN, -OH, -SF ₅ , -SH, -S(=O)C ₁ -C ₃ alkyl, -S(=O) ₂ C ₁ -C ₃ alkyl, -S(=O) ₂ NH ₂ , -S(=O) ₂ NHC ₁ -C ₃ alkyl, - S(=O) ₂ N(C ₁ -C ₃ alkyl) ₂ , -S(=O)(=NC ₁ -C ₃ alkyl)(C ₁ -C ₃ alkyl), -NH ₂ , -NHC ₁ -C ₃ alkyl, -N(C ₁ -C ₃ alkyl) ₂ , - N=S(=O)(C1-C3alkyl)2, -C(=O)C1-C3alkyl, -C(=O)OH, -C(=O)OC1-C3alkyl, -C(=O)NH2, -C(=O)NHC1- C3alkyl, -C(=O)N(C1-C3alkyl)2, -P(=O)(C1-C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1- C3haloalkoxy, C1-C3hydroxyalkyl, C1-C3aminoalkyl, C1-C3heteroalkyl, or C3-C6cycloalkyl; or two R on the same atom form an oxo. In some embodiments of a compound disclosed herein, each R is independently halogen, -CN, -OH, -NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, -C(=O)C1-C3alkyl, - C(=O)OH, -C(=O)OC1-C3alkyl, -C(=O)NH2, -C(=O)NHC1-C3alkyl, -C(=O)N(C1-C3alkyl)2, C1-C3alkyl, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkyl, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ hydroxyalkyl, C ₁ -C ₃ aminoalkyl, C ₁ -C ₃ heteroalkyl, ^{or C} 3 ^-C 6 ^{cycloalkyl; or two R on the same atom form an oxo. In some embodiments of a compound} disclosed herein, each R is independently halogen, -CN, -OH, -NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, C1- C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, or C1-C3haloalkoxy; or two R on the same atom form an oxo. In some embodiments of a compound disclosed herein, each R is independently halogen, -CN, -OH, -NH ₂ , C1-C3alkyl, C1-C3alkoxy, or C1-C3haloalkyl; or two R on the same atom form an oxo. In some embodiments of a compound disclosed herein, each R is independently halogen, -CN, -OH, -NH2, C1- C3alkyl, or C1-C3haloalkyl; or two R on the same atom form an oxo. In some embodiments of a compound disclosed herein, each R is independently halogen, C ₁ -C ₃ alkyl, or C ₁ -C ₃ haloalkyl; or two R on the same atom form an oxo. [00206] In some embodiments of a compound disclosed herein, each R is independently halogen, -CN, -OH, -NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, -C(=O)C1-C3alkyl, -C(=O)OH, -C(=O)OC1-C3alkyl, - C(=O)NH ₂ , -C(=O)NHC ₁ -C ₃ alkyl, -C(=O)N(C ₁ -C ₃ alkyl) ₂ , C ₁ -C ₃ alkyl, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkyl, C ₁ - ^C 3 ^{haloalkoxy, C} 1 ^-C 3 ^{hydroxyalkyl, C} 1 ^-C 3 ^{aminoalkyl, C} 1 ^-C 3 ^{heteroalkyl, or C} 3 ^-C 6 ^{cycloalkyl. In some} embodiments of a compound disclosed herein, each R is independently halogen, -CN, -OH, -NH2, - NHC1-C3alkyl, -N(C1-C3alkyl)2, -C(=O)C1-C3alkyl, -C(=O)OH, -C(=O)OC1-C3alkyl, -C(=O)NH2, - C(=O)NHC ₁ -C ₃ alkyl, -C(=O)N(C ₁ -C ₃ alkyl) ₂ , or C ₁ -C ₃ alkyl. In some embodiments of a compound disclosed herein, each R is independently halogen, -NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, -C(=O)C1- C3alkyl, -C(=O)OH, -C(=O)OC1-C3alkyl, -C(=O)NH2, -C(=O)NHC1-C3alkyl, or -C(=O)N(C1-C3alkyl)2. In some embodiments of a compound disclosed herein, each R is independently halogen, -NH ₂ , -NHC ₁ - C ₃ alkyl, or -N(C ₁ -C ₃ alkyl) ₂ . In some embodiments of a compound disclosed herein, each R is independently halogen, -C(=O)C1-C3alkyl, -C(=O)OH, -C(=O)OC1-C3alkyl, -C(=O)NH2, -C(=O)NHC1- C3alkyl, or -C(=O)N(C1-C3alkyl)2. [00207] In some embodiments, the compound disclosed herein, or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, is selected from a compound found in table 1: Table 1

* stereochemistry arbitrarily assigned. After chiral separation, pure structures are isolated but the absolute configuration of the stereochemical center is unknown. [00208] In some embodiments, the compound disclosed herein, is selected from a racemic compound selected from the group consisting of:

, , pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof. Further Forms of Compounds Disclosed Herein Isomers/Stereoisomers [00209] In some embodiments, the compounds described herein exist as geometric isomers. In some embodiments, the compounds described herein possess one or more double bonds. The compounds presented herein include all cis, trans, syn, anti, entgegen (E), and zusammen (Z) isomers as well as the corresponding mixtures thereof. In some situations, the compounds described herein possess one or more chiral centers and each center exists in the R configuration or S configuration. The compounds described herein include all diastereomeric, enantiomeric, and epimeric forms as well as the corresponding mixtures thereof. In additional embodiments of the compounds and methods provided herein, mixtures of enantiomers and/or diastereoisomers, resulting from a single preparative step, combination, or interconversion are useful for the applications described herein. In some embodiments, the compounds described herein are prepared as their individual stereoisomers by reacting a racemic mixture of the compound with an optically active resolving agent to form a pair of diastereoisomeric compounds, separating the diastereomers, and recovering the optically pure enantiomers. In some embodiments, dissociable complexes are preferred. In some embodiments, the diastereomers have distinct physical properties (e.g., melting points, boiling points, solubilities, reactivity, etc.) and are separated by taking advantage of these dissimilarities. In some embodiments, the diastereomers are separated by chiral chromatography, or preferably, by separation/resolution techniques based upon differences in solubility. In some embodiments, the optically pure enantiomer is then recovered, along with the resolving agent. Labeled compounds [00210] In some embodiments, the compounds described herein exist in their isotopically-labeled forms. In some embodiments, the methods disclosed herein include methods of treating diseases by administering such isotopically-labeled compounds. In some embodiments, the methods disclosed herein include methods of treating diseases by administering such isotopically-labeled compounds as pharmaceutical compositions. Thus, in some embodiments, the compounds disclosed herein include isotopically-labeled compounds, which are identical to those recited herein, but for the fact that one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number usually found in nature. Examples of isotopes that can be incorporated into compounds described herein, or a solvate, or stereoisomer thereof, include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, sulfur, fluorine, and chloride, such as ² H, ³ H, ¹³ C, ¹⁴ C, ^l5 N, ¹⁸ O, ¹⁷ O, ³¹ P, ^{32P, 35S, 18F, and 36Cl, respectively. Compounds described herein, and the pharmaceutically acceptable} salts, solvates, or stereoisomers thereof which contain the aforementioned isotopes and/or other isotopes of other atoms are within the scope of this disclosure. Certain isotopically-labeled compounds, for example those into which radioactive isotopes such as ³ H and ¹⁴ C are incorporated, are useful in drug and/or substrate tissue distribution assays. Tritiated, i.e., ³ H and carbon-14, i.e., ¹⁴ C, isotopes are particularly preferred for their ease of preparation and detectability. Further, substitution with heavy isotopes such as deuterium, i.e., ² H, produces certain therapeutic advantages resulting from greater metabolic stability, for example increased in vivo half-life or reduced dosage requirements. [00211] In some embodiments, the abundance of deuterium in each of the substituents disclosed herein is independently at least 1%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100% of a total number of hydrogen and deuterium. In some embodiments, one or more of the substituents disclosed herein comprise deuterium at a percentage higher than the natural abundance of deuterium. In some embodiments, one or more hydrogens are replaced with one or more deuteriums in one or more of the substituents disclosed herein. [00212] In some embodiments, the isotopically labeled compound or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof is prepared by any suitable method. [00213] In some embodiments, the compounds described herein are labeled by other means, including, but not limited to, the use of chromophores or fluorescent moieties, bioluminescent labels, or chemiluminescent labels. Pharmaceutically acceptable salts [00214] In some embodiments, the compounds described herein exist as their pharmaceutically acceptable salts. In some embodiments, the methods disclosed herein include methods of treating diseases by administering such pharmaceutically acceptable salts. In some embodiments, the methods disclosed herein include methods of treating diseases by administering such pharmaceutically acceptable salts as pharmaceutical compositions. [00215] In some embodiments, the compounds described herein possess acidic or basic groups and therefore react with any of a number of inorganic or organic bases, and inorganic and organic acids, to form a pharmaceutically acceptable salt. In some embodiments, these salts are prepared in situ during the final isolation and purification of the compounds disclosed herein, or a solvate, or stereoisomer thereof, or by separately reacting a purified compound in its free form with a suitable acid or base, and isolating the salt thus formed. [00216] Examples of pharmaceutically acceptable salts include those salts prepared by reaction of the compounds described herein with a mineral, organic acid or inorganic base, such salts including, but not limited to, acetate, acrylate, adipate, alginate, aspartate, benzoate, benzenesulfonate, bisulfate, bisulfite, bromide, butyrate, butyn-1,4-dioate, camphorate, camphorsulfonate, caproate, caprylate, chlorobenzoate, chloride, citrate, cyclopentanepropionate, decanoate, digluconate, gluconate, dihydrogenphosphate, dinitrobenzoate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptanoate, glycerophosphate, glycolate, hemisulfate, heptanoate, hexanoate, hexyne-1,6-dioate, hydroxybenzoate, γ-hydroxybutyrate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonate, iodide, isobutyrate, lactate, maleate, malonate, methanesulfonate, mandelate metaphosphate, methoxybenzoate, methylbenzoate, monohydrogenphosphate, 1-napthalenesulfonate, 2-napthalenesulfonate, nicotinate, nitrate, palmoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, pyrosulfate, pyrophosphate, propiolate, phthalate, phenylacetate, phenylbutyrate, propanesulfonate, salicylate, succinate, sulfate, sulfite, succinate, suberate, sebacate, sulfonate, tartrate, thiocyanate, tosylate, undecanoate, and xylenesulfonate. [00217] Further, the compounds described herein can be prepared as pharmaceutically acceptable salts formed by reacting the free base form of the compound with a pharmaceutically acceptable inorganic or organic acid, including, but not limited to, inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid metaphosphoric acid, and the like; and organic acids such as acetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, p- toluenesulfonic acid, tartaric acid, trifluoroacetic acid, citric acid, benzoic acid, 3-(4- hydroxybenzoyl)benzoic acid, cinnamic acid, mandelic acid, arylsulfonic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 2- naphthalenesulfonic acid, 4-methylbicyclo-[2.2.2]oct-2-ene-1-carboxylic acid, glucoheptonic acid, 4,4’- methylenebis-(3-hydroxy-2-ene-1-carboxylic acid), 3-phenylpropionic acid, trimethylacetic acid, tertiary butylacetic acid, lauryl sulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid and muconic acid. In some embodiments, other acids, such as oxalic, while not in themselves pharmaceutically acceptable, are employed in the preparation of salts useful as intermediates in obtaining the compounds disclosed herein, solvate, or stereoisomer thereof and their pharmaceutically acceptable acid addition salts. [00218] In some embodiments, those compounds described herein which comprise a free acid group react with a suitable base, such as the hydroxide, carbonate, bicarbonate, sulfate, of a pharmaceutically acceptable metal cation, with ammonia, or with a pharmaceutically acceptable organic primary, secondary, tertiary, or quaternary amine. Representative salts include the alkali or alkaline earth salts, like lithium, sodium, potassium, calcium, and magnesium, and aluminum salts and the like. Illustrative examples of bases include sodium hydroxide, potassium hydroxide, choline hydroxide, sodium carbonate, N ⁺ (C1-C4 alkyl)4 hydroxide, and the like. [00219] Representative organic amines useful for the formation of base addition salts include ethylamine, diethylamine, ethylenediamine, ethanolamine, diethanolamine, piperazine and the like. It should be understood that the compounds described herein also include the quaternization of any basic nitrogen-containing groups they contain. In some embodiments, water or oil-soluble or dispersible products are obtained by such quaternization. Solvates [00220] In some embodiments, the compounds described herein exist as solvates. The disclosure provides for methods of treating diseases by administering such solvates. The disclosure further provides for methods of treating diseases by administering such solvates as pharmaceutical compositions. [00221] Solvates contain either stoichiometric or non-stoichiometric amounts of a solvent, and, in some embodiments, are formed with pharmaceutically acceptable solvents such as water, ethanol, and the like. Hydrates are formed when the solvent is water, or alcoholates are formed when the solvent is alcohol. Solvates of the compounds described herein can be conveniently prepared or formed during the processes described herein. In addition, the compounds provided herein can exist in unsolvated as well as solvated forms. In general, the solvated forms are considered equivalent to the unsolvated forms for the purposes of the compounds and methods provided herein. Tautomers [00222] In some situations, compounds exist as tautomers. The compounds described herein include all possible tautomers within the formulas described herein. Tautomers are compounds that are interconvertible by migration of a hydrogen atom, accompanied by a switch of a single bond and adjacent double bond. In bonding arrangements where tautomerization is possible, a chemical equilibrium of the tautomers will exist. All tautomeric forms of the compounds disclosed herein are contemplated. The exact ratio of the tautomers depends on several factors, including temperature, solvent, and pH. Preparation of the Compounds [00223] The compounds used in the reactions described herein are made according to organic synthesis techniques known to those skilled in this art, starting from commercially available chemicals and/or from compounds described in the chemical literature. “Commercially available chemicals” are obtained from standard commercial sources including Acros Organics (Pittsburgh, PA), Aldrich Chemical (Milwaukee, WI, including Sigma Chemical and Fluka), Apin Chemicals Ltd. (Milton Park, UK), Avocado Research (Lancashire, U.K.), BDH, Inc. (Toronto, Canada), Bionet (Cornwall, U.K.), Chem Service Inc. (West Chester, PA), Crescent Chemical Co. (Hauppauge, NY), Eastman Organic Chemicals, Eastman Kodak Company (Rochester, NY), Fisher Scientific Co. (Pittsburgh, PA), Fisons Chemicals (Leicestershire, UK), Frontier Scientific (Logan, UT), ICN Biomedicals, Inc. (Costa Mesa, CA), Key Organics (Cornwall, U.K.), Lancaster Synthesis (Windham, NH), Maybridge Chemical Co. Ltd. (Cornwall, U.K.), Parish Chemical Co. (Orem, UT), Pfaltz & Bauer, Inc. (Waterbury, CN), Polyorganix (Houston, TX), Pierce Chemical Co. (Rockford, IL), Riedel de Haen AG (Hanover, Germany), Spectrum Quality Product, Inc. (New Brunswick, NJ), TCI America (Portland, OR), Trans World Chemicals, Inc. (Rockville, MD), and Wako Chemicals USA, Inc. (Richmond, VA). [00224] Suitable reference books and treatises that detail the synthesis of reactants useful in the preparation of compounds described herein, or provide references to articles that describe the preparation, include for example, “Synthetic Organic Chemistry”, John Wiley & Sons, Inc., New York; S. R. Sandler et al., “Organic Functional Group Preparations,” 2nd Ed., Academic Press, New York, 1983; H. O. House, “Modern Synthetic Reactions”, 2nd Ed., W. A. Benjamin, Inc. Menlo Park, Calif.1972; T. L. Gilchrist, “Heterocyclic Chemistry”, 2nd Ed., John Wiley & Sons, New York, 1992; J. March, “Advanced Organic Chemistry: Reactions, Mechanisms and Structure”, 4th Ed., Wiley-Interscience, New York, 1992. Additional suitable reference books and treatises that detail the synthesis of reactants useful in the preparation of compounds described herein, or provide references to articles that describe the preparation, include for example, Fuhrhop, J. and Penzlin G. “Organic Synthesis: Concepts, Methods, Starting Materials”, Second, Revised and Enlarged Edition (1994) John Wiley & Sons ISBN: 3-527-29074-5; Hoffman, R.V. “Organic Chemistry, An Intermediate Text” (1996) Oxford University Press, ISBN 0-19-509618-5; Larock, R. C. “Comprehensive Organic Transformations: A Guide to Functional Group Preparations” 2nd Edition (1999) Wiley-VCH, ISBN: 0-471-19031-4; March, J. “Advanced Organic Chemistry: Reactions, Mechanisms, and Structure” 4th Edition (1992) John Wiley & Sons, ISBN: 0-471-60180-2; Otera, J. (editor) “Modern Carbonyl Chemistry” (2000) Wiley-VCH, ISBN: 3-527-29871-1; Patai, S. “Patai's 1992 Guide to the Chemistry of Functional Groups” (1992) Interscience ISBN: 0-471-93022-9; Solomons, T. W. G. “Organic Chemistry” 7th Edition (2000) John Wiley & Sons, ISBN: 0-471-19095-0; Stowell, J.C., “Intermediate Organic Chemistry” 2nd Edition (1993) Wiley-Interscience, ISBN: 0-471- 57456-2; “Industrial Organic Chemicals: Starting Materials and Intermediates: An Ullmann's Encyclopedia” (1999) John Wiley & Sons, ISBN: 3-527-29645-X, in 8 volumes; “Organic Reactions” (1942-2000) John Wiley & Sons, in over 55 volumes; and “Chemistry of Functional Groups” John Wiley & Sons, in 73 volumes. [00225] Specific and analogous reactants are optionally identified through the indices of known chemicals prepared by the Chemical Abstract Service of the American Chemical Society, which are available in most public and university libraries, as well as through on-line. Chemicals that are known but not commercially available in catalogs are optionally prepared by custom chemical synthesis houses, where many of the standard chemical supply houses (e.g., those listed above) provide custom synthesis services. A reference for the preparation and selection of pharmaceutical salts of the compounds described herein is P. H. Stahl & C. G. Wermuth “Handbook of Pharmaceutical Salts”, Verlag Helvetica Chimica Acta, Zurich, 2002. Pharmaceutical Compositions [00226] In certain embodiments, the compound described herein is administered as a pure chemical. In some embodiments, the compound described herein is combined with a pharmaceutically suitable or acceptable carrier (also referred to herein as a pharmaceutically suitable (or acceptable) excipient, physiologically suitable (or acceptable) excipient, or physiologically suitable (or acceptable) carrier) selected on the basis of a chosen route of administration and standard pharmaceutical practice as described, for example, in Remington: The Science and Practice of Pharmacy (Gennaro, 21 ^st Ed. Mack Pub. Co., Easton, PA (2005)). [00227] Accordingly, provided herein is a pharmaceutical composition comprising a compound described herein, or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, and a pharmaceutically acceptable excipient. [00228] In certain embodiments, the compound provided herein is substantially pure, in that it contains less than about 5%, or less than about 1%, or less than about 0.1%, of other organic small molecules, such as unreacted intermediates or synthesis by-products that are created, for example, in one or more of the steps of a synthesis method. [00229] Pharmaceutical compositions are administered in a manner appropriate to the disease to be treated. An appropriate dose and a suitable duration and frequency of administration will be determined by such factors as the condition of the patient, the type and severity of the patient's disease, the particular form of the active ingredient, and the method of administration. In general, an appropriate dose and treatment regimen provides the composition(s) in an amount sufficient to provide therapeutic and/or prophylactic benefit (e.g., an improved clinical outcome, such as more frequent complete or partial remissions, or longer disease-free and/or overall survival, or a lessening of symptom severity. Optimal doses are generally determined using experimental models and/or clinical trials. The optimal dose depends upon the body mass, weight, or blood volume of the patient. [00230] In some embodiments, the pharmaceutical composition is formulated for oral, topical (including buccal and sublingual), rectal, vaginal, transdermal, parenteral, intrapulmonary, intradermal, intrathecal, and epidural and intranasal administration. Parenteral administration includes intramuscular, intravenous, intraarterial, intraperitoneal, or subcutaneous administration. In some embodiments, the pharmaceutical composition is formulated for intravenous injection, oral administration, inhalation, nasal administration, topical administration, or ophthalmic administration. In some embodiments, the pharmaceutical composition is formulated for oral administration. In some embodiments, the pharmaceutical composition is formulated for intravenous injection. In some embodiments, the pharmaceutical composition is formulated as a tablet, a pill, a capsule, a liquid, an inhalant, a nasal spray solution, a suppository, a suspension, a gel, a colloid, a dispersion, a suspension, a solution, an emulsion, an ointment, a lotion, an eye drop, or an ear drop. In some embodiments, the pharmaceutical composition is formulated as a tablet. [00231] Suitable doses and dosage regimens are determined by conventional range-finding techniques known to those of ordinary skill in the art. Generally, treatment is initiated with smaller dosages that are less than the optimum dose of the compound disclosed herein. Thereafter, the dosage is increased by small increments until the optimum effect under the circumstances is reached. Methods of Treatment [00232] The compounds disclosed herein, or pharmaceutically acceptable salts, solvates, or stereoisomers thereof, are useful for the inhibition of TREX1. [00233] Provided herein are compounds that are inhibitors of TREX1 and are therefore useful for treating one or more disorders associated with the activity of TREX1 or mutants thereof. [00234] Provided herein is a method of treating cancer in a subject in need thereof, the method comprising administering a compound disclosed herein, or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof. In some embodiments, the cancer is selected from non-Hodgkin lymphoma, Hodgkin lymphoma, squamous cell carcinoma, cancer of the head and neck, cholangiocarcinoma, hepatocellular carcinoma, bladder cancer, sarcoma, colon cancer, gastric cancer, thyroid cancer, lung cancer, leukemia, pancreatic cancer, melanoma, multiple myeloma, brain cancer, CNS cancer, renal cancer, prostate cancer, ovarian cancer, and breast cancer. [00235] In some embodiments, the cancer is a solid tumor malignancy. In some embodiments, the solid tumor malignancy is bone cancer (for example, but not limited to, chondrosarcoma, Ewing's sarcoma, malignant fibrous histiocytoma of bone/osteosarcoma, osteosarcoma, or rhabdomyosarcoma), heart cancer, brain and nervous system cancer (for example, but not limited to, astrocytoma, brainstem glioma, pilocytic astrocytoma, ependymoma, primitive neuroectodermal tumor, cerebellar astrocytoma, cerebral astrocytoma, glioma, medulloblastoma, glioblastoma, neuroblastoma, oligodendroglioma, pineal astrocytoma, pituitary adenoma, or visual pathway and hypothalamic glioma), breast cancer (for example, but not limited to, invasive lobular carcinoma, tubular carcinoma, invasive cribriform carcinoma, medullary carcinoma, male breast cancer, phyllodes tumor, or inflammatory breast cancer), endocrine system cancer (for example, but not limited to, adrenocortical carcinoma, islet cell carcinoma (endocrine pancreas), multiple endocrine neoplasia syndrome, parathyroid cancer, pheochromocytoma, or thyroid cancer), eye cancer (for example, but not limited to, uveal melanoma or retinoblastoma), gastrointestinal cancer (for example, but not limited to, anal cancer, appendix cancer, cholangiocarcinoma, gastrointestinal carcinoid tumor, colon cancer, extrahepatic bile duct cancer, gallbladder cancer, gastric (stomach) cancer, gastrointestinal carcinoid tumor, gastrointestinal stromal tumor (gist), hepatocellular cancer, pancreatic cancer, or rectal cancer), genitourinary and gynecologic cancer (for example, but not limited to, bladder cancer, cervical cancer, endometrial cancer, extragonadal germ cell tumor, ovarian cancer, ovarian epithelial cancer (surface epithelial-stromal tumor), ovarian germ cell tumor, penile cancer, renal cell carcinoma, renal pelvis and ureter, transitional cell cancer, prostate cancer, testicular cancer, gestational trophoblastic tumor, ureter and renal pelvis, transitional cell cancer, urethral cancer, uterus cancer, uterine sarcoma, vaginal cancer, vulvar cancer, or Wilms tumor), head and neck cancer (for example, but not limited to, is esophageal cancer, nasopharyngeal carcinoma, oral cancer, oropharyngeal cancer, paranasal sinus and nasal cavity cancer, pharyngeal cancer, salivary gland cancer, or hypopharyngeal cancer), skin cancer (for example, but not limited to, basal cell carcinoma, squamous cell carcinoma, skin adnexal tumors (e.g. sebaceous carcinoma), melanoma, Merkel cell carcinoma, or sarcomas of primary cutaneous origin (e.g. dermatofibrosarcoma protuberans)), or thoracic and respiratory cancer (bronchial adenomas/carcinoid, small cell lung cancer, mesothelioma, non-small cell lung cancer, pleuropulmonary blastoma, laryngeal cancer, or thymoma and thymic carcinoma). [00236] TREX1 is a component of the cellular DNA repair mechanism. Treatment of patients with cancers having DNA repair deficiencies (such as BRCA1 mutations) with DNA repair inhibitors (such as poly ADP ribose polymerase (“PARP”) inhibitors) is synergistic due to the dramatically reduced probability of developing resistance against two DNA repair insults; this approach is known as synthetic lethality. Hence, TREX1 inhibitors also possess potential utility as effective synthetic lethality partners in patients with cancers characterized by defective DNA repair. [00237] In some embodiments, the DNA repair deficiency is a deficiency in the base excision repair (“BER”) pathway (such as a PolB mutation). In some embodiments, the DNA repair deficiency is a deficiency in the Fanconi anaemia-mediated repair (“FA”) pathway (such as an FANCA mutation). In some embodiments, the DNA repair deficiency is a deficiency in the homologous recombination (“HR”) pathway (such as a BRCA1 mutation). In some embodiments, the DNA repair deficiency is a deficiency in the nucleotide excision repair (“NER”) pathway (such as an XPA mutation). In some embodiments, the DNA repair deficiency is a deficiency in the non-homologous end joining (“NHEJ”) pathway (such as an MRE11 mutation). In some embodiments, the DNA repair deficiency is a deficiency in the mismatch repair (“MMR”) pathway (such as an hMSH2 mutation). In some embodiments, the DNA repair deficiency is a deficiency in the RecQ-mediated repair (“RecQ”) pathway (such as a BLM mutation). In some embodiments, the DNA repair deficiency is a deficiency in the double-stranded breaks (“DSB”) pathway (such as a POLQ mutation). [00238] In some embodiments, the cancer is characterized by a deficiency in one or more DNA repair pathways. In some embodiments, the DNA repair deficiency is a deficiency in the base excision repair (“BER”) pathway, the Fanconi anaemia-mediated repair (“FA”) pathway, the homologous recombination (“HR”) pathway, the nucleotide excision repair (“NER”) pathway, the non-homologous end joining (“NHEJ”) pathway, the mismatch repair (“MMR”) pathway, the RecQ-mediated repair (“RecQ”) pathway, or the double-stranded breaks (“DSB”) pathway. In some embodiments, the DNA repair deficiency is a deficiency in the homologous recombination (“HR”) pathway. In some embodiments, the DNA repair deficiency is a BRCA1 mutation. [00239] Provided herein is a method of treating cancer in a subject in need thereof, the method comprising administering a reversible, non-competitive TREX1 inhibitor. In some embodiments, the cancer is a solid tumor malignancy. In some embodiments, the cancer is selected from non-Hodgkin lymphoma, Hodgkin lymphoma, squamous cell carcinoma, cancer of the head and neck, cholangiocarcinoma, hepatocellular carcinoma, bladder cancer, sarcoma, colon cancer, gastric cancer, thyroid cancer, lung cancer, leukemia, pancreatic cancer, melanoma, multiple myeloma, brain cancer, CNS cancer, renal cancer, prostate cancer, ovarian cancer, and breast cancer. [00240] Provided herein is a method of increasing type I interferon production in a subject in need thereof, the method comprising administering a reversible, non-competitive TREX1 inhibitor. In some embodiments, the increase in type I interferon production occurs in the tumor microenvironment. In some embodiments, the TREX1 inhibitor is administered systemically. In some embodiments, the TREX1 inhibitor comprises a compound disclosed herein, or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof. [00241] Provided herein is a method of treating an HIV infection in a subject in need thereof, the method comprising administering a compound disclosed herein, or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof. [00242] Human immunodeficiency virus (HIV) is a retrovirus and causative agent of acquired immune deficiency syndrome (AIDS). Productive infection of CD4+ T cells requires successful reverse transcription of the single-stranded viral RNA genome. The resulting dsDNA undergoes 3’ processing before stable integration into the host genome. Only a small percentage of infectious particles complete reverse transcription successfully. Abortive reverse transcription from the remaining viral particles results in accumulation of cDNA intermediates, yet chronic HIV infection does not induce an interferon response. The 3’ exonuclease activity of TREX1 prevents the accumulation of reverse transcribed HIV-1 DNA to avoid the interferon response. In addition, TREX1 processing of the 3’end of HIV-1 DNA in the pre integration complex is critical for successful HIV-1 integration. In some embodiments, treatment strategies to reduce or inhibit TREX1 promote both antiviral immunity and have direct antiviral effects by reducing productive integration. Combination Therapy [00243] In certain instances, the compound described herein, or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, is administered in combination with a second therapeutic agent. [00244] In some embodiments, the benefit experienced by a patient is increased by administering one of the compounds described herein with a second therapeutic agent (which also includes a therapeutic regimen) that also has therapeutic benefit. [00245] In one specific embodiment, a compound described herein, or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, is co-administered with a second therapeutic agent, wherein the compound described herein, or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, and the second therapeutic agent modulate different aspects of the disease, disorder or condition being treated, thereby providing a greater overall benefit than administration of either therapeutic agent alone. [00246] In any case, regardless of the disease, disorder or condition being treated, the overall benefit experienced by the patient is simply additive of the two therapeutic agents or the patient experiences a synergistic benefit. [00247] In certain embodiments, different therapeutically effective dosages of the compounds disclosed herein will be utilized in formulating a pharmaceutical composition and/or in treatment regimens when the compounds disclosed herein are administered in combination with a second therapeutic agent. Therapeutically effective dosages of drugs and other agents for use in combination treatment regimens are optionally determined by means similar to those set forth hereinabove for the actives themselves. Furthermore, the methods of treatment described herein encompasses the use of metronomic dosing, i.e., providing more frequent, lower doses in order to minimize toxic side effects. In some embodiments, a combination treatment regimen encompasses treatment regimens in which administration of a compound described herein, or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, is initiated prior to, during, or after treatment with a second agent described herein, and continues until any time during treatment with the second agent or after termination of treatment with the second agent. It also includes treatments in which a compound described herein, or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, and the second agent being used in combination are administered simultaneously or at different times and/or at decreasing or increasing intervals during the treatment period. Combination treatment further includes periodic treatments that start and stop at various times to assist with the clinical management of the patient. [00248] It is understood that the dosage regimen to treat or ameliorate the condition(s) for which relief is sought, is modified in accordance with a variety of factors (e.g. the disease, disorder, or condition from which the subject suffers; the age, weight, sex, diet, and medical condition of the subject). Thus, in some instances, the dosage regimen actually employed varies and, in some embodiments, deviates from the dosage regimens set forth herein. [00249] For combination therapies described herein, dosages of the co-administered compounds vary depending on the type of co-drug employed, on the specific drug employed, on the disease or condition being treated, and so forth. In additional embodiments, when co-administered with a second therapeutic agent, the compound provided herein is administered either simultaneously with the second therapeutic agent, or sequentially. [00250] In combination therapies, the multiple therapeutic agents (one of which is one of the compounds described herein) are administered in any order or even simultaneously. If administration is simultaneous, the multiple therapeutic agents are, by way of example only, provided in a single, unified form, or in multiple forms (e.g., as a single pill or as two separate pills). [00251] The compounds described herein, or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, as well as combination therapies, are administered before, during, or after the occurrence of a disease or condition, and the timing of administering the composition containing a compound varies. In another embodiment, the compounds and compositions are administered to a subject during or as soon as possible after the onset of the symptoms. In specific embodiments, a compound described herein is administered as soon as is practicable after the onset of a disease or condition is detected or suspected, and for a length of time necessary for the treatment of the disease. In some embodiments, the length required for treatment varies, and the treatment length is adjusted to suit the specific needs of each subject. For example, in specific embodiments, a compound described herein or a formulation containing the compound is administered for at least 2 weeks, about 1 month to about 5 years. [00252] In some embodiments, the compound described herein, or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, is administered in combination with an adjuvant. In one embodiment, the therapeutic effectiveness of one of the compounds described herein is enhanced by administration of an adjuvant (i.e., by itself the adjuvant has minimal therapeutic benefit, but in combination with another therapeutic agent, the overall therapeutic benefit to the patient is enhanced). [00253] In some embodiments, the compound described herein, or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, is administered in combination with a DNA repair inhibitor. In some embodiments, the DNA repair inhibitor is a poly ADP ribose polymerase (“PARP”) inhibitor. In some embodiments, the PARP inhibitor is olaparib, rucaparib, niraparib, talazoparib, veliparib, pamiparib, CEP 9722, or E7016. [00254] In some embodiments, the compound described herein, or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, is administered in combination with an alkylating agent. In some embodiments, the alkylating agent is cyclophosphamide, chlormethine, uramustine, melphalan, chlorambucil, ifosfamide, bendamustine, carmustine, lomustine, nimustine, fotemustine, streptozocin, or busulfan. [00255] In some embodiments, the compound described herein, or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, is administered in conjunction with radiation therapy. In some embodiments, the radiation therapy is administered on a standard fractionation, an accelerated fractionation, a hyperfractionation, or a hypofractionation schedule. [00256] In some embodiments, the compound described herein, or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, increases anti-tumor immunity when combined with radiation therapy. [00257] In some embodiments, the compound described herein, or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, modulates intratumoral immune infiltrate in tumors when combined with radiation therapy. [00258] In some embodiments, the compound described herein, or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, improves tumor control when combined with radiation therapy. [00259] In some embodiments, the compound described herein, or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, when combined with tumor-directed radiotherapy enhances systemic anti-tumor immune responses as measured by blood-based immune markers, modulation of intratumoral infiltrate in non-irradiated (abscopal) tumors and tumor control in non-irradiated tumors. [00260] In some embodiments, the radiation therapy is tumor-directed radiation therapy. In some embodiments, the radiation therapy is metastasis-directed radiation therapy. [00261] In some embodiments the radiation therapy is external beam radiation therapy. External beam radiation therapy is a local treatment, which means it treats a specific part of the body. In some embodiments, the external beam radiation therapy is from a photon beam. In some embodiments, the external beam radiation therapy is from a proton beam. In some embodiments, the external beam radiation therapy is from an electron beam. [00262] In some embodiments, the external beam radiation therapy is 3-D conformal radiation therapy. 3-D conformal radiation therapy is a type of external beam radiation therapy. It uses images from CT, MRI, and PET scans to precisely plan the treatment area, a process called simulation. A computer program is used to analyze the images and to design radiation beams that conform to the shape of the tumor. [00263] In some embodiments, the external beam radiation therapy is intensity-modulated radiation therapy (IMRT). In some embodiments, the external beam radiation therapy is image-guided radiation therapy (IGRT). IGRT is a type of IMRT using imaging scans not only for treatment planning before radiation therapy sessions but also during radiation therapy sessions. [00264] In some embodiments, the external beam radiation therapy is tomotherapy®. Tomotherapy® is a type of IMRT that uses a machine that is a combination of a CT scanner and an external-beam radiation machine. [00265] In some embodiments, the external beam radiation therapy is stereotactic radiosurgery: Stereotactic radiosurgery is the use of focused, high-energy beams to treat small tumors with well- defined edges in the brain and central nervous system. GammaKnife is a type of stereotactic radiosurgery. [00266] In some embodiments, the external beam radiation therapy is stereotactic body radiation therapy (SBRT). Stereotactic body radiation therapy is similar to stereotactic radiosurgery, but it is used for small, isolated tumors outside the brain and spinal cord. [00267] In some embodiments the radiation therapy is internal radiation therapy. Internal radiation therapy is a treatment in which a source of radiation is put inside the body. The radiation source can be solid or liquid. Internal radiation therapy with a solid source is called brachytherapy. In this type of treatment, seeds, ribbons, or capsules that contain a radiation source are placed in the body, in or near the tumor. Like external beam radiation therapy, brachytherapy is a local treatment and treats only a specific part of your body. [00268] In some embodiments, the brachytherapy is low-dose rate (LDR) implants. [00269] In some embodiments, the brachytherapy is high-dose rate (HDR) implants. [00270] In some embodiments, the brachytherapy is permanent implants. After the radiation source is put in place, the catheter is removed. The implants remain in the body for the rest of the patient’s life, but the radiation gets weaker each day. As time goes on, almost all the radiation will go away. [00271] In some embodiments, the compound described herein, or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, is administered in conjunction with high-dose radiotherapy administered as a single dose and/or hypofractionated. [00272] In some embodiments, the compound described herein, or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, is administered in conjunction with Stereotactic Body Radiation Therapy (SBRT). EXAMPLES Example 1: 6-(benzo[d]oxazol-2-yl)-2-(1-cyclobutyl-6-(2H-tetrazol-5-yl) -1H-benzo[d]imidazol-2-yl)- 5-hydroxy-3-methylpyrimidin-4(3H)-one [00273] Step 1: To a stirred solution of ethyl 2-(diethoxymethyl)-5-ethoxy-1-methyl-6-oxo-1,6- dihydropyrimidine-4-carboxylate (2 g, 6.09 mmol) in a mixture of THF (26.7 mL, 328 mmol) and water (13.3 mL, 740 mmol) was added lithiumhydroxide monohydrate (307 mg, 1.2 eq., 7.31 mmol). The reaction mixture was stirred at ambient temperature for 30 min at which time the mixture was concentration, diluted with water, and extracted with ether. The aqueous layer was acidified using 0.5 N HCl and extracted with EtOAc (50 mLX3). The combined organic layer washed with the brine and dried over anhydrous sodium sulfate. Concentration provided 2-(diethoxymethyl)-5-ethoxy-1-methyl-6-oxo- 1,6-dihydropyrimidine-4-carboxylic acid (1.8 g, 94% yield). ES MS M/Z = 301.1 [M+H] ⁺ . [00274] Step 2: To a stirred solution of 2-(diethoxymethyl)-5-ethoxy-1-methyl-6-oxo-1,6- dihydropyrimidine-4-carboxylic acid (1.8 g, 5.99 mmol) in DMF (2 mL) was added HATU (3.42 g, 1.5 eq., 8.99 mmol) , DIPEA (4.19 mL, 4 eq., 24 mmol) .The reaction mixture was stirred at ambient temperature for 1 h, the reaction mixture was poured into water and extracted with ethyl acetate. The combined organics were dried over sodium sulfate, filtered, and concentrated to afford crude, The crude was purified by flash column chromatography to afford 2-(diethoxymethyl)-5-ethoxy-N-(2- hydroxyphenyl)-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carbox amide (1.2 g, 44%). ES MS M/Z = 392.2 [M+H] ⁺ . [00275] Step 3: To a stirred solution of 2-(diethoxymethyl)-5-ethoxy-N-(2-hydroxyphenyl)-1-methyl- 6-oxo-1,6-dihydropyrimidine-4-carboxamide (1.2 g, 3.07 mmol) in THF (20 mL, 246 mmol) was added triphenylphosphane (2.01 g, 2.5 eq., 7.66 mmol) and N-{[(propan-2-yloxy)carbonyl]imino}(propan-2- yloxy)formamide (3.87 g, 2.5 eq., 7.66 mmol) . The reaction was stirred at 80 ° C 16 h. Progress of the reaction monitored by TLC and LCMS. The reaction mixture was diluted with water, extracted with EtOAc (20 mL X3).The combined organic layers were washed with the brine and dried over anhydrous sodium sulfate. Concentration provided compound which was purified by flash column chromatography to afford 6-(1,3-benzoxazol-2-yl)-2-(diethoxymethyl)-5-ethoxy-3-methyl -3,4-dihydropyrimidin-4-one (1.3 g, 56% yield ). ES MS M/Z = 374.1 [M+H] ⁺ . [00276] Step 4: A solution of 6-(1,3-benzoxazol-2-yl)-2-(diethoxymethyl)-5-ethoxy-3-methyl -3,4- dihydropyrimidin-4-one (1 g, 2.68 mmol) in formic acid (13.3 mL, 351 mmol) was heated to 85 ° C for 3 h . The reaction mixture was concentrated, washed with NaHCO3, and extracted with EtOAc ( 3 x 10 mL ) , and the combined organic layers were dried over sodium sulfate, and concentrated to yield crude product which was purified by CombiFlash (eluted at 50% EA in Hexane ) to yield 4-(1,3-benzoxazol-2- yl)-5-ethoxy-1-methyl-6-oxo-1,6-dihydropyrimidine-2-carbalde hyde (320 mg, 27% yield ) . ES MS M/Z = 300.0 [M+H] ⁺ . [00277] Step 5: To a stirred solution of N1-cyclobutyl-5-(2H-1,2,3,4-tetrazol-5-yl)benzene-1,2-diamin e (0.1 g, 0.434 mmol) and 4-(1,3-benzoxazol-2-yl)-5-ethoxy-1-methyl-6-oxo-1,6-dihydrop yrimidine-2- carbaldehyde (130 mg, 0.434 mmol) in a mixture of DMF (1 mL) and water (0.3 mL) was added oxone monopersulfate (133 mg, 0.434 mmol). The reaction was stirred for 1 h at ambient temperature. Progress of the reaction monitored by TLC and LCMS. The mixture was diluted with water and extracted with the ethyl acetate (10 mL X2). The combined organic layers were washed with the brine and dried over anhydrous sodium sulfate. Concentration provided crude product , The crude was purified by flash column chromatography to afford 6-(1,3-benzoxazol-2-yl)-2-[1-cyclobutyl-6-(2H-1,2,3,4-tetraz ol-5-yl)- 1H-1,3-benzodiazol-2-yl]-5-ethoxy-3-methyl-3,4-dihydropyrimi din-4-one (110 mg, 49% yield ). ES MS M/Z = 510.2 [M+H] ⁺ . [00278] Step 6: A stirred solution of 6-(1,3-benzoxazol-2-yl)-2-[1-cyclobutyl-6-(2H-1,2,3,4-tetraz ol-5- yl)-1H-1,3-benzodiazol-2-yl]-5-ethoxy-3-methyl-3,4-dihydropy rimidin-4-one (90 mg, 0.177 mmol) in DCM (418 µL, 6.53 mmol) was cooled to -40 °C. Tribromoborane (22.6 µL, 3 eq., 0.132 mmol) was added and the mixture was stirred at ambient temperature for 4 h, The reaction was monitored by TLC and LCMS . The reaction was quenched with MeOH (1 mL), concentrated, and the crude product was purified by reverse phase column chromatography to yield 6-(1,3-benzoxazol-2-yl)-2-[1-cyclobutyl-6- (2H-1,2,3,4-tetrazol-5-yl)-1H-1,3-benzodiazol-2-yl]-5-hydrox y-3-methyl-3,4-dihydropyrimidin-4-one (14 mg, 16% yield ). ES MS M/Z = 482.2 [M+H] ⁺ , UPLC: 99%; ¹ H NMR (400 MHz, DMSO-d6) δ ppm: ¹ H NMR (400 MHz, DMSO-d6) δ ppm: 8.54 (s, 1 H), 8.08-8.00(m, 2 H), 7.91-7.83 (m,2 H), 7.52-7.46 (m, 2 H), 5.35-5.31 (m, 1 H), 3.58 ( s , 3 H ), 2.79-2.74 ( m , 4 H ) , 1.95- 1.83 (m, 2 H). Examples 2, 3, and 4: 6-(1,3-benzoxazol-2-yl)-2-{[cyclobutyl(phenyl)methyl](methyl )amino}-5- hydroxy-3-methyl-3,4-dihydropyrimidin-4-one [00279] Step 1: To a stirred solution of cyclobutanecarbaldehyde (1.7 g, 20.2 mmol) in dry THF (34 mL, 418 mmol), phenyllithium (1.7 g, 20.2 mmol) was added at -50 °C and the mixture was stirred at ambient temperature for 16 h. After completion, the reaction mixture was quenched with ammonium chloride solution and extracted with ethyl acetate, washed with brine, and dried over anhydrous sodium sulfate to provide the crude. The crude compound was purified by CombiFlash chromatography (10 - 20% EtOAc in heptane) to provide cyclobutyl(phenyl)methanol (2.7 g, 74%). [00280] Step 2: To a stirred solution of cyclobutyl(phenyl)methanol (2.7 g, 16.6 mmol) in DCM (67.5 mL, 1.05 mol) and 1,1-bis(acetyloxy)-3-oxo-3H-1λ⁵,2-benziodaoxol-1-yl acetate (9.18 g, 1.3 eq., 21.6 mmol) was added under 0 °C and stirred at ambient temperature for 1 h. After completion, the reaction mixture was quenched with sodium bicarbonate solution and extracted with DCM and combined organic layers were washed with brine and dried over anhydrous sodium sulfate to provide the crude product which was purified by CombiFlash chromatography (10 - 20% EtOAc in heptane) to provide the cyclobutyl(phenyl)methanone (2.4 g, 88%). ES MS M/Z = 161.0 [M+H] ⁺ . [00281] Step 3: To a stirred solution of cyclobutyl(phenyl)methanone (2.4 g, 15 mmol) in formic acid (10 mL) and formamide (2.99 mL, 5 eq., 74.9 mmol) was added at 0 °C and the mixture was stirred at 185 °C for 16 h. The reaction was monitored by TLC & LCMS. After completion, the reaction mixture was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with brine and dried over anhydrous sodium sulfate to provide the crude N- [cyclobutyl(phenyl)methyl]formamide (2.5 g, 71%). ES MS M/Z = 190.2 [M+H] ⁺ . [00282] Step 4: In a sealed tube, N-[cyclobutyl(phenyl)methyl]formamide (2.5 g, 13.2 mmol) and aqueous 30% hydrogen chloride (3 mL) was heated at 110 °C for 2 h. After cooling to ambient temperature, water was added. The reaction mixture was carefully adjusted to pH 10 with aqueous NaOH (33%) and extracted with ethyl acetate, dried over sodium sulfate, and concentrated under reduced pressure to provide cyclobutyl(phenyl)methanamine (1.7 g, crude). ES MS M/Z = 162.0 [M+H] ⁺ . [00283] Step 5: To a stirred solution of methyl 2-chloro-5-methoxy-1-methyl-6-oxo-1,6- dihydropyrimidine-4-carboxylate (2.5 g, 10.7 mmol), 1-cyclobutyl-1-phenylmethanamine (1.73 g, 10.7 mmol) in DMSO (1 mL) and DIPEA (3.75 mL, 2 eq., 21.5 mmol) was added and stirred at 110 °C for 16 h. The reaction mixture was diluted with water, extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude compound was purified by CombiFlash to provide the methyl 2-{[cyclobutyl(phenyl)methyl]amino}-5-methoxy-1-methyl-6-oxo -1,6-dihydropyrimidine-4- carboxylate (3.1 g, 72.63%). ES MS M/Z = 358.5 [M+H] ⁺ . [00284] Step 6: To a stirred solution of methyl 2-{[cyclobutyl(phenyl)methyl]amino}-5-methoxy-1- methyl-6-oxo-1,6-dihydropyrimidine-4-carboxylate (3 g, 8.39 mmol) in DMF (22.5 mL, 291 mmol), cesium carbonate (8.2 g, 3 eq., 25.2 mmol) and iodomethane (1.05 mL, 2 eq., 16.8 mmol) was added and the mixture was stirred at ambient temperature for 1 h. The reaction mixture was diluted with water and extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and concentrated to afford methyl 2-((cyclobutyl(phenyl)methyl)(methyl)amino)-5-methoxy-1-meth yl-6-oxo-1,6- dihydropyrimidine-4-carboxylate (2.8 g, 74.54%). ES MS M/Z = 372.0 [M+H] ⁺ . [00285] Step 7: To a stirred solution of methyl 2-{[cyclobutyl(phenyl)methyl] (methyl)amino}-5- methoxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxylate (2.8 g, 7.54 mmol) in methanol (5mL), THF (32 mL) and water (3 mL) was added lithium hydroxide (1.58 g, 5 eq., 37.7 mmol) at ambient temperature and the mixture was stirred for 3 h. After completion, the reaction mixture was concentrated under reduced pressure. The crude was dissolved in water and acidified with 1N HCl solution to pH~5, extracted with DCM, and dried over anhydrous sodium sulfate to provide the crude 2- {[cyclobutyl(phenyl)methyl](methyl)amino}-5-methoxy-1-methyl -6-oxo-1,6-dihydropyrimidine-4- carboxylic acid (2.5 g, 88.15%). ES MS M/Z = 358.0 [M+H] ⁺ . [00286] Step 8: To a stirred solution of 2-{[cyclobutyl(phenyl)methyl](methyl)amino}-5-methoxy-1- methyl-6-oxo-1,6-dihydropyrimidine-4-carboxylic acid (1.8 g, 5.04 mmol) in DMF (18 mL, 232 mmol), DIPEA (2.79 mL, 3 eq., 15.1 mmol), HATU (2.87 g, 1.5 eq., 7.55 mmol) and 2-iodoaniline (1.21 g, 1.1 eq., 5.54 mmol) was added and the mixture was stirred at ambient temperature for 3 h. After completion of the reaction, it was diluted with ice water and extracted with ethyl acetate , washed with brine, and dried over anhydrous sodium sulfate to provide the crude. The crude compound was purified by CombiFlash provide the 2-{[cyclobutyl(phenyl)methyl](methyl)amino}-N-(2-iodophenyl) -5-methoxy-1- methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide (1.8 g, 47%). ES MS M/Z = 559.0 [M+H] ⁺ . [00287] Step 9: To a stirred solution of 2-{[cyclobutyl(phenyl)methyl](methyl)amino}-N-(2- iodophenyl)-5-methoxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4 -carboxamide (1.8 g, 3.22 mmol) in acetonitrile (51.4 mL, 985 mmol), cesium carbonate (1.58 g, 1.5 eq., 4.84 mmol) was added and the mixture was purged with nitrogen for 5 minutes. Then λ¹-copper (1+) iodide (30.7 mg, 0.05 eq., 161 µmol) and 1,10-phenanthroline (58.1 mg, 0.1 eq., 322 µmol) was added and the mixture was purged again with nitrogen for 5 minutes. The reaction mixture was then stirred at 110 °C for 16 h. After completion of the reaction it was diluted with water, extracted with EtOAc, washed with brine, and dried over anhydrous sodium sulfate to provide the crude which was purified by CombiFlash then chiral preparative HPLC to afford (R)-6-(benzo[d]oxazol-2-yl)-2-((cyclobutyl(phenyl)methyl)(me thyl)amino)- 5-methoxy-3-methylpyrimidin-4(3H)-one (0.1 g) ES MS M/Z = 431.1 [M +1] ⁺ (S)-6-(benzo[d]oxazol-2- yl)-2-((cyclobutyl(phenyl)methyl)(methyl)amino)-5-methoxy-3- methylpyrimidin-4(3H)-one (0.1 g) ES MS M/Z = 431.1 [M+H] ⁺ . [00288] Step 10: To a stirred solution of 6-(1,3-benzoxazol-2-yl)-2- {[cyclobutyl(phenyl)methyl](methyl)amino}-5-methoxy-3-methyl -3,4-dihydropyrimidin-4-one (150 mg, 348 µmol) in DMF (15 mL) was added lithium bromide (242 mg, 8 eq., 2.79 mmol) at ambient temperature. The mixture was heated at 110 °C for 16 h. After completion of the reaction, the mixture was diluted with saturated ammonium chloride, extracted with the DCM, the combined organic layers were washed with brine, dried over anhydrous sodium sulfate, and concentrated to provide the crude product which was purified by CombiFlash to provide the 6-(1,3-benzoxazol-2-yl)-2- {[cyclobutyl(phenyl)methyl] (methyl)amino}-5-hydroxy-3-methyl-3,4-dihydropyrimidin-4-one (12 mg, 8%). ES MS M/Z = 417.3 [M+H] ⁺ , UPLC: 98.01%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.45 (bs, 1 H), 7.91 - 7.88 (m, 2 H), 7.52 - 7.45 (m, 4 H), 7.38 - 7.32 (m, 2 H), 7.26 - 7.23 (m, 1 H), 4.67 - 4.64 (m, 1 H), 3.59 (s, 3 H), 3.2-3.13 (m, 1 H), 2.61 (s, 3 H), 1.98 (s, 1 H), 1.8 - 1.59 (m, 5 H). [00289] Step 11: To a stirred solution of (R)-6-(benzo[d]oxazol-2-yl)-2- ((cyclobutyl(phenyl)methyl)(methyl)amino)-5-methoxy-3-methyl pyrimidin-4(3H)-one (0.1 g, 232 µmol) in DMF (2 mL, 25.8 mmol) was added lithium bromide (202 mg, 10 eq., 2.32 mmol) at ambient temperature. The mixture was heated at 110 °C for 16 h. After completion of the reaction, the reaction mixture was diluted with saturated ammonium chloride and extracted with the DCM, dried over anhydrous sodium sulfate, and concentrated to provide the crude product which washed with pentane to provide 6-(1,3-benzoxazol-2-yl)-2-{[cyclobutyl(phenyl)methyl](methyl )amino}-5-hydroxy-3-methyl- 3,4-dihydropyrimidin-4-one (0.04 g, 41%). ES MS M/Z = 417.3 [M+H] ⁺ , UPLC: 98.01%; ¹ H NMR (400 MHz, DMSO-d6) δ 10.29 (bs, 1 H), 7.87 (m, 2 H), 7.51 - 7.49 (m, 4 H), 7.35 - 7.31 (m, 2 H), 7.26 - 7.22 (m, 1 H), 4.64 (m, 1 H), 3.63 (s, 3 H), 2.91 - 2.89 (m, 1 H), 2.59 (s, 3 H), 1.96 - 1.91 (m, 1 H), 1.79 (m, 2 H), 1.68 - 1.6 (m, 3 H). [00290] Step 12: To a stirred solution of (S)-6-(benzo[d]oxazol-2-yl)-2- ((cyclobutyl(phenyl)methyl)(methyl)amino)-5-methoxy-3-methyl pyrimidin-4(3H)-one (0.1 g, 232 µmol) in DMF (2 mL, 25.8 mmol) was added lithium bromide (202 mg, 10 eq., 2.32 mmol) at ambient temperature. The mixture was heated at 110 °C for 16 h. After completion of the reaction, reaction mixture was diluted with saturated ammonium chloride and extracted with the DCM, washed with brine, and dried over anhydrous sodium sulfate, concentrated. The crude was purified by prep HPLC condition to provide 6-(1,3-benzoxazol-2-yl)-2-{[cyclobutyl(phenyl)methyl](methyl )amino}-5-hydroxy-3-methyl- 3,4-dihydropyrimidin-4-one (0.012 g, 13%). ES MS M/Z = 417.3 [M+H] ⁺ , UPLC: 100%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.44 (bs, 1 H), 7.88 - 7.91 (m, 2 H), 7.45 - 7.52 (m, 4 H), 7.32 - 7.35 (m, 2 H), 7.23 - 7.26 (m, 1 H), 4.64 - 4.67 (m, 1 H), 3.59 (s, 3 H), 3.13 - 3.17 (m, 1 H), 2.61 (s, 3 H), 1.99 (m, 1 H), 1.59 - 1.76 (m, 5 H). Example 5, 6, and 7: Synthesis of 6-(1,3-benzoxazol-2-yl)-2-{[(2-chlorophenyl) (phenyl)methyl] (methyl)amino}-5-hydroxy-3-methyl-3,4-dihydropyrimidin-4-one [00291] Step 1: To a stirred solution of 2-chlorobenzaldehyde (2.5 mL, 21.3 mmol) in DCM (30 mL, 469 mmol) was added cesium carbonate (10.4 g, 1.5 eq., 32 mmol) and 2-methylpropane-2-sulfinamide (3.1 g, 1.2 eq., 25.6 mmol) and the mixture was stirred at 40 °C for 16 h. After completion, the mixture was diluted with water and the compound was extracted with DCM. The organic layer dried over anhydrous sodium sulfate, filtered, and concentrated to provide crude product which was purified by CombiFlash chromatography (0-5% EtOAc in Heptane) to provide N-[(Z)-(2- chlorophenyl)methylidene]-2-methylpropane-2-sulfinamide (3.8 g, 73.05%). LC-MS(ES)m/z: 244.1 [M+H] ⁺ . [00292] Step 2: To a stirred solution of N-[(Z)-(2-chlorophenyl) methylidene]-2-methylpropane-2- sulfinamide (3 g, 12.3 mmol) in THF (35.5 mL, 436 mmol) at -78 °C was added phenyl lithium (1.24 g, 1.2 eq., 14.8 mmol) and the mixture was stirred at ambient temperature for 6 h. After completion, the reaction mixture was quenched with ammonium chloride solution and extracted with EtOAc. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to provide crude compound which was purified by CombiFlash chromatography (15 - 40% EtOAc in Heptane) to provide the N-[(2- chlorophenyl)(phenyl)methyl]-2-methylpropane-2-sulfinamide (3.8 g, 96%). LC-MS(ES)m/z: 322.1 [M+H] ⁺ . [00293] Step 3: To a stirred solution of N-[(2-chlorophenyl)(phenyl)methyl]-2-methylpropane-2- sulfinamide (2 g, 6.21 mmol) in DCM (20 mL), hydrogen chloride (453 mg, 2 eq., 12.4 mmol) was added at 0 °C and the mixture was stirred for 16 h. The solvent was removed under pressure to provide the crude which washed with n-Pentane then dried to afford 1-(2-chlorophenyl)-1-phenylmethanamine hydrochloride (1.4 g, 89%). ¹ H NMR (400 MHz, DMSO-d6) δ ppm: 9.15 (s, 2H), 7.87 (d, J = 8 Hz, 1H), 7.51 (t, J = Hz, 2H), 7.42-7.35 (m, 6H). [00294] Step 4: To a stirred solution of 1-(2-chlorophenyl)-1-phenylmethanamine hydrochloride (1.4 g, 5.51 mmol) and methyl 2-chloro-5-methoxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-ca rboxylate (1.28 g, 5.51 mmol) in DMSO (10 mL) was added ethylbis(propan-2-yl) amine (2.88 mL, 3 eq., 16.5 mmol) and stirred the mixture was stirred at 110 °C for 2 h in the microwave. After completion, the reaction mixture was diluted with water and extracted with EtOAc. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to provide crude. The crude was purified by flash chromatography to afford methyl2-{[(2-chlorophenyl) (phenyl)methyl] amino}-5-methoxy-1-methyl-6- oxo-1,6-dihydropyrimidine-4-carboxylate (1.9 g, 83%). LC-MS(ES)m/z: 414.1 [M+H] ⁺ . [00295] Step 5: To a stirred solution of methyl 2-{[(2-chlorophenyl) (phenyl)methyl] amino}-5- methoxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxylate (1.7 g, 4.11 mmol) in DMF (20 mL), cesium carbonate (2.01 g, 1.5 eq., 6.16 mmol) and iodomethane (0.256 mL, 4.11 mmol) were added and the mixture was stirred at ambient temperature for 2 h. After completion, the reaction mixture was diluted with ice water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product which was purified by flash chromatography to afford methyl 2-{[(2-chlorophenyl) (phenyl)methyl] (methyl)amino}-5-methoxy-1- methyl-6-oxo-1,6-dihydropyrimidine-4-carboxylate (2 g, 97%). LC-MS(ES)m/z: 428.1 [M+H] ⁺ . [00296] Step 6: To a stirred solution of methyl 2-{[(2-chlorophenyl) (phenyl)methyl] (methyl)amino}- 5-methoxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxylate (0.5 g, 1.17 mmol) in methanol (20 mL), THF (12 mL), water (8 mL) was added lithium hydrate hydroxide (981 mg, 5 eq., 23.4 mmol) at ambient temperature and the mixture was stirred for 1 h. After completion, the mixture was concentrated under reduced pressure. The crude was dissolved in water and acidified with 1N HCl solution up to pH~2. The compound was extracted using EtOAc and the combined organic layers were dried over anhydrous sodium sulfate to provide the crude 2-{[(2-chlorophenyl) (phenyl)methyl] (methyl)amino}-5- methoxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxylic acid (1.4 g, 73%) as yellow viscous liquid. LC-MS(ES)m/z: 414.0 [M+H] ⁺ . [00297] Step 7: To a stirred solution of 2-{[(2-chlorophenyl) (phenyl)methyl] (methyl)amino}-5- methoxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxylic acid (0.7 g, 1.69 mmol) and 2-iodoaniline (445 mg, 1.2 eq., 2.03 mmol) in DMF (10 mL) was added DIPEA (0.937 mL, 3 eq., 5.07 mmol) and HATU (965 mg, 1.5 eq., 2.54 mmol). The resultant reaction mixture was allowed to stir at ambient temperature for 3 h. After completion, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to afford crude. Crude compound was purified by CombiFlash (eluted with 0-20% EtOAc-Hexane gradient) to afford 2-{[(2-chlorophenyl) (phenyl)methyl] (methyl)amino}-N-(2-iodophenyl)-5-methoxy-1-methyl- 6-oxo-1,6-dihydropyrimidine-4-carboxamide (950 mg, 91%). LC-MS(ES)m/z: 579.1 [M+H] ⁺ . [00298] Step 8: To a stirred solution of 2-{[(2-chlorophenyl)(phenyl)methyl](methyl)amino}-N-(2- iodophenyl)-5-methoxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4 -carboxamide (850 mg, 1.38 mmol) in acetonitrile (17 mL, 325 mmol), was added cesium carbonate (676 mg, 1.5 eq., 2.07 mmol), 1,10- phenanthroline (24.9 mg, 0.1 eq., 0.138 mmol) and copper iodide (26.3 mg, 0.1 eq., 0.138 mol). The resultant reaction mixture was allowed to stir at 110 °C for 1.5 h. After completion, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to afford the crude product which was purified by Combi-flash (eluted with 0-35% EtOAc-Hexane gradient) to afford 6-(1,3-benzoxazol-2-yl)-2-{[(2-chlorophenyl) (phenyl)methyl] (methyl)amino}-5-methoxy-3-methyl-3,4-dihydropyrimidin-4-one (0.5 g, 74%) as a yellow solid. LC-MS(ES)m/z: 487.0 [M+H] ⁺ . [00299] Step 9: To a solution of 6-(1,3-benzoxazol-2-yl)-2-{[(2-chlorophenyl) (phenyl)methyl](methyl)amino}-5-methoxy-3-methyl-3,4-dihydro pyrimidin-4-one (0.5 g, 1.03 mmol) in DMF (3 mL, 38.7 mmol) was added lithium bromide (446 mg, 5 eq., 5.13 mmol) the mixture was stirred at 100 °C for 16 h.. After completion of the reaction, the mixture was diluted with saturated ammonium chloride and extracted with EtOAc. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, and concentrated to provide the crude. The crude compound was purified by preparative HPLC to afford 6-(1,3-benzoxazol-2-yl)-2-{[(2-chlorophenyl) (phenyl)methyl] (methyl)amino}-5-hydroxy-3-methyl-3,4-dihydropyrimidin-4-one (184 mg, 37.89%). LC-MS(ES)m/z: 473.3 [M+H] ⁺ ; ¹ H NMR (400 MHz, DMSO d ₆ ) δ ppm: 10.51 (s, 1H), 7.84 (d, J = 8Hz, 2H), 7.66 (d, J = 8Hz, 1H), 7.57 (d, J = 8Hz, 2H), 7.52-7.44 (m, 2H), 7.36-7.30 (m, 3H), 7.28-7.22 (m, 2H), 7.16-7.12 (m, H), 3.68 (s, 3H), 2.59 (s, 3H). Chiral separation of Synthesis of 6-(1,3-benzoxazol-2-yl)-2-{[(2-chlorophenyl) (phenyl)methyl] (methyl)amino}-5-hydroxy-3-methyl-3,4-dihydropyrimidin-4-one : Chiral method: [00300] Analytical Conditions: Column : Chiralpak IG ( 250 mm X 20 mm X 5 mic) Mobile phase: n Hexane : Ethanol in 0.1% FA (50:50) Flow rate : 18 mL/min Isomer-1 [00301] LCMS(ESI), m/z: 473.3 [M+H] ⁺ ; ¹ H NMR (400 MHz, DMSO d6) δ ppm: 10.51 ( s, 1H), 7.84 (d, J = 8Hz, 2H), 7.66 (d, J = 8Hz, 1H), 7.57 (d, J = 8Hz, 2H), 7.52-7.44 (m , 2H), 7.36-7.30 (m, 2H), 7.28-7.22 (m, 4H), 7.16-7.12 (m, 1H), 3.68 (s, 3H), 2.58 (s, 3H). Isomer-2 [00302] LCMS(ESI), m/z: 473.3 [M+H] ⁺ ; ¹ H NMR (400 MHz, DMSO d6) δ ppm: 10.52 (s, 1H), 7.84 (d, J= 8Hz, 2H), 7.66 (d, J = 8Hz, 1H), 7.57 (d, J = 8Hz, 2H), 7.52-7.43 (m , 2H), 7.36-7.25 (m, 5H), 7.16-7.12 (m, 1H), 3.68 (s, 3H), 2.58 (s, 3H). Example 8: 4-({[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6-di hydropyrimidin-2- yl](methyl)amino}(phenyl)methyl)benzoic acid [00303] Step 1: To a stirred solution of 4-bromobenzaldehyde (3 g, 16.2 mmol) and 2-methylpropane- 2-sulfinamide (1.97 g, 16.2 mmol) in THF (60 mL) was added titanium tetraethanolate (10.2 mL, 3 eq., 48.6 mmol) and the mixture was stirred at ambient temperature for 16 h. After completion, brine was added into the reaction mixture and it was stirred for 10 minutes, filtered through the celite bed, and washed with ethyl acetate. Then the organic layer washed with ethyl acetate, dried over anhydrous sodium sulfate, and concentrated to provide the crude. The crude compound was purified by CombiFlash (10 - 15% ethyl acetate in heptane) to provide the N-[(Z)-(4-bromophenyl) methylidene]-2- methylpropane-2-sulfinamide (3.2 g, 68%). [00304] Step 2: To a stirred solution of N-[(Z)-(4-bromophenyl) methylidene]-2-methylpropane-2- sulfinamide (2 g, 6.94 mmol) in THF (20 mL) was added phenyllithium (0.583 g, 6.94 mmol) at -78 °C and the mixture was stirred at ambient temperature for 6 h. After completion, the reaction mixture was quenched with ammonium chloride solution and extracted with ethyl acetate. Combined organic layers were washed with brine and dried over anhydrous sodium sulfate to provide the crude. The crude compound was purified by CombiFlash chromatography (15 - 20% ethyl acetate in heptane) to provide the N-[(4-bromophenyl) (phenyl)methyl]-2-methylpropane-2-sulfinamide (1.88 g, 74%) as a colorless solid. ES MS M/Z = 368.1[M+2H] ⁺ . [00305] Step 3: To a stirred solution of N-[(4-bromophenyl) (phenyl)methyl]-2-methylpropane-2- sulfinamide (1.88 g, 5.13 mmol) in DCM (13.8 mL, 215 mmol), hydrogen chloride (0.374 g, 10.3 mmol) was added at 0 °C and stirred for 1 h. After completion, the reaction mixture was evaporated under reduced pressure to provide the crude. The crude compound washed with n-pentane for 3 times and dried to afford 1-(4-bromophenyl)-1-phenylmethanamine hydrochloride (1.8 g, 99%). ¹ H NMR (400 MHz, DMSO-d6) δ ppm: 9.28 (s, 2 H), 7.65 (m, 2 H), 7.55 (m, 4H), 7.4 (m, 2 H), 7.6 (m, 1H), 5.6 (s, 1H). [00306] Step 4: To a stirred solution of 1-(4-bromophenyl)-1-phenylmethanamine hydrochloride (1.88 g, 6.3 mmol) and methyl 2-chloro-5-methoxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-ca rboxylate (1.76 g, 1.2 eq., 7.56 mmol) in DMSO (11.4 mL, 160 mmol) was added DIPEA (1.64 mL, 1.5 eq., 9.44 mmol) and the mixture was stirred at 120 °C for 2 h. After completion, the reaction mixture was quenched with water and extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate to provide the crude. The crude compound was purified by CombiFlash chromatography (40% ethyl acetate in heptane) to provide the methyl 2-{[(4- bromophenyl)(phenyl)methyl]amino}-5-methoxy-1-methyl-6-oxo-1 ,6-dihydropyrimidine-4-carboxylate (1.73 g, 60%). ES MS M/Z=459.9 [M+H] ⁺ . [00307] Step 5: To a stirred solution of methyl 2-{[(4-bromophenyl) (phenyl)methyl] amino}-5- methoxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxylate (1.73 g, 3.77 mmol) in DMF (60 mL), was added cesium carbonate (1.84 g, 5.66 mmol) and iodomethane (0.258 mL, 4.15 mmol) and the mixture was stirred at ambient temperature for 2 h. The reaction mixture was diluted with ice water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude (1.65 g, 92%). ES MS M/Z= 472.1 [M+H] ⁺ . [00308] Step 6: To a stirred solution of methyl 2-{[(4-bromophenyl) (phenyl)methyl] (methyl)amino}- 5-methoxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxylate (1.65 g, 3.49 mmol) in a mixture of methanol (10 mL), THF (4 mL) and water (3 mL) was added lithium hydroxide (0.44 g, 10.5 mmol) at ambient temperature and the mixture was stirred for 1 h. After completion, the reaction mixture was concentrated under reduced pressure. The crude was dissolved in water and acidified with 1N HCl solution to pH~2. The solid precipitate was filtered and dried to provide 2-{[(4-bromophenyl) (phenyl)methyl](methyl)amino}-5-methoxy-1-methyl-6-oxo-1,6-d ihydropyrimidine-4-carboxylic acid (1.3 g, 81%). ES MS M/Z= 458.0 [M+H] ⁺ . [00309] Step 7: To a stirred solution of 2-{[(4-bromophenyl) (phenyl)methyl] (methyl)amino}-5- methoxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxylic acid (1.3 g, 2.84 mmol) and 2-iodoaniline (0.746 g, 3.4 mmol) in DMF (20 mL) was added DIPEA (1.57 mL, 8.51 mmol) and 1- [Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b] pyridinium 3-oxid hexafluorophosphate (1.62 g, 4.25 mmol) and the mixture was stirred at ambient temperature for 3 h. After completion, the reaction mixture was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with brine and dried over anhydrous sodium sulfate to provide the crude. The crude compound was purified by CombiFlash to provide 2-{[(4-bromophenyl)(phenyl)methyl](methyl)amino}-N-(2- iodophenyl)-5-methoxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4 -carboxamide (1.15 g, 58%). ES MS M/Z=661.0 [M+2H] ⁺ . [00310] Step 8: To a stirred solution of 2-{[(4-bromophenyl) (phenyl)methyl] (methyl)amino}-N-(2- iodophenyl)-5-methoxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4 -carboxamide (1.15 g, 1.74 mmol) in acetonitrile (30 mL, 587 mmol) was added cesium carbonate (0.852 g, 2.62 mmol) copper iodide (0.016 g, 872 mmol), and 1,10-phenanthroline (0.031 g, 174 mmol). The mixture was then purged with nitrogen for 10 min and stirred at 110 °C for 16 h. After completion of the reaction, the mixture was diluted with water and extracted into ethyl acetate. The combined organic layers were washed with brine and dried over anhydrous sodium sulfate to provide the crude. The crude compound was purified by CombiFlash to provide the 6-(1,3-benzoxazol-2-yl)-2-{[(4-bromophenyl) (phenyl)methyl] (methyl)amino}-5-methoxy- 3-methyl-3,4-dihydropyrimidin-4-one (0.4 g, 38%). ES MS M/Z=531.0 [M+H] ⁺ . [00311] Step 9: To a stirred solution of 6-(1,3-benzoxazol-2-yl)-2-{[(4-bromophenyl) (phenyl)methyl] (methyl)amino}-5-methoxy-3-methyl-3,4-dihydropyrimidin-4-one (0.2 g, 376 mmol) in 1,2- dimethoxyethane (5 mL) and water (2 mL), sodium carbonate (59.8 mg, 565 mmol) was added to the reaction mixture, followed by the addition of tetrafluoroboranuide, tri-tert-butylphosphanium (10.9 mg, 3.76 mmol) and hexakis(methanidylidyneoxidanium) molybdenum (149 mg, 565 mmol). The mixture was purged with nitrogen gas for 10 min then palladium diacetate (8.45 mg, 3.76 mmol) was added and the mixture was and stirred in the microwave for 1 h at 120 °C. After completion, the solvent was evaporated and the residue was diluted with water and washed with ethyl acetate. The aqueous layer was acidified with 1N H1 solution (pH~2) and extracted with DCM. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure to provide crude compound which was purified by CombiFlash to provide the 4-({[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2-yl] (methyl)amino} (phenyl)methyl) benzoic acid (0.2 g, 89%). ES MS M/Z=497.0 [M+H] ⁺ , [00312] Step 10: To a stirred solution of 4-({[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2-yl] (methyl)amino} (phenyl)methyl) benzoic acid (0.1 g, 0.201 mmol) in DMF (15 mL) was added lithium bromide (105 mg, 1.21 mmol) at ambient temperature and the mixture was stirred at 100 °C for 16 h. After completion of the reaction, the reaction mixture was diluted with saturated ammonium chloride and extracted with the DCM. Combined organic layers were washed with brine, dried over anhydrous sodium sulfate, and concentrated to provide the crude. The crude compound was purified by preparative HPLC to afford 4-({[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2-yl] (methyl)amino} (phenyl)methyl) benzoic acid (8 mg, 8%). ES MS M/Z=483.2 [M+H] ⁺ ; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ ppm: 12.82 (bs, 1H), 10.57 (bs, 1 H), 7.86 (s, 4 H), 7.61 (m, 2 H), 7.5 (m, 4 H), 7.33 (m, 2 H), 7.19 (m, 1 H), 5.81 (s, 1 H), 3.73 (s, 3 H), 2.59 (s, 3 H). [00313] The following compounds were synthesized in a similar manner: Example 10: 3-({[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6-di hydropyrimidin-2- yl](methyl)amino}(phenyl)methyl)benzoic acid ES MS M/Z =483.3 [M+H] ⁺ ; ¹ H NMR (400 MHz, DMSO-d6) δ ppm: 12.93 (bs, 1H), 10.51 (bs, 1 H), 8.03 (s, 1H), 7.85-7.83 (t, J= 8 Hz, 2H), 7.73-7.71 (d, J=8 Hz, 2H), 7.52-7.30 (m, 7H), 7.23-7.19 (m, 1H), 5.83 (s, 1H), 3.68 (s, 3H), 2.67 (s, 3H). Example 49: 6-(1,3-benzoxazol-2-yl)-2-{[(3-fluorophenyl) (phenyl)methyl] (methyl)amino}-5- hydroxy-3-methyl-3,4-dihydropyrimidin-4-one LC-MS(ES)m/z: 457.4 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO d6) δ ppm: 10.55 (s, 1H), 7.86 (d, J = 8.4Hz, 2H), 7.52-7.44 (m, 4H), 7.36-7.28 (m, 5H), 7.20-7.17 (m, 1H), 7.01-6.96 (m, 1H), 5.76 (s, 1H), 3.69 (s, 3H), 2.59 (s, 3H). Example 9: 4-(((4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6-di hydropyrimidin-2- yl)(methyl)amino)(phenyl)methyl)benzamide [00314] Step 1: A solution of 6-(1,3-benzoxazol-2-yl)-2-{[(4-bromophenyl) (phenyl)methyl] (methyl)amino}-5-methoxy-3-methyl-3,4-dihydropyrimidin-4-one (0.1 g, 0.188 mol) in DMF (10 mL) was purged with nitrogen for 5 minutes then zinc cyanide (0.044 mg, 0.376 mmol) was added followed by [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II ), complex with DCM (0.013 mg, 0.0188 mmol) and the mixture was heated at 150 °C for 4 h. After completion, water was added and the mixture was extracted with ethyl acetate, dried over magnesium sulfate, and concentrated under reduced pressure to provide crude product which was purified by CombiFlash to provide the 4-({[4-(1,3-benzoxazol-2-yl)- 5-methoxy-1-methyl-6-oxo-1,6-dihydropyrimidin-2-yl](methyl)a mino}(phenyl)methyl)benzonitrile (0.065 g, 72%). ES MS M/Z=478.0 [M+H] ⁺ . [00315] Step 2: To a stirred solution of 4-({[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2-yl] (methyl)amino} (phenyl)methyl) benzonitrile (0.065 g, 0.136 mmol) in DMSO (2 mL) was added 20% hydrogen peroxide (0.047 mL, 0.204 mmol) and potassium carbonate (0.094 g, 0.681 mmol) at 0 °C and the mixture was stirred at ambient temperature for 16 h. After completion, the reaction mixture was poured in water and a solid precipitate was formed which was filtered to afford 4- ({[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxo-1,6-dihy dropyrimidin-2-yl] (methyl)amino} (phenyl)methyl) benzamide (0.040 g, 59%). ES MS M/Z=496.2 [M+H] ⁺ . [00316] Step 3: To a stirred solution of 4-({[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2-yl] (methyl)amino} (phenyl)methyl) benzamide (0.055 g, 0.111 mmol) in DMF (2 mL) was added lithium bromide (0.096 g, 1.11 mmol) at ambient temperature. The mixture was heated at 110 °C for 16 h. After completion of the reaction, the reaction mixture was diluted with saturated ammonium chloride and extracted with the DCM. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, and concentrated to provide the crude compound which was purified by preparative HPLC using analytical preparative HPLC to afford 4-(((4-(benzo[d]oxazol-2-yl)- 5-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidin-2-yl)(methyl)a mino)(phenyl)methyl)benzamide (0.011 g, 20%). ES MS M/Z=482.3 [M+H] ⁺ ; ¹ H NMR (400 MHz, DMSO-d6) δ ppm: 10.56 (bs, 1 H), 7.86 (s, 3 H), 7.75 (m, 2 H), 7.5 (m, 6 H), 7.30 (m, 3 H), 7.19 (m, 1 H), 5.80 (s, 1 H), 3.69 (s, 3 H), 2.59 (s, 3 H). Example 11: Synthesis of 6-(1,3-benzoxazol-2-yl)-2-(1-cyclobutyl-1H-1,3-benzodiazol-2 -yl)-5- hydroxy-3-methyl-3,4-dihydropyrimidin-4-one [00317] Step 1: To a stirred solution of 1-fluoro-2-nitrobenzene (3.4 mL, 35.4 mmol) in 1- methylpyrrolidin-2-one (5 mL), DIPEA (18.5 mL, 106 mmol) and cyclobutanamine (3.64 mL, 42.5 mmol) was added and the mixture was stirred at 120 ºC for 16 h. After completion of the reaction, the mixture was diluted with ethyl acetate, washed with water and brine, dried over sodium sulfate, filtered, and concentrated. The crude was purified by flash column chromatography to afford N-cyclobutyl-2- nitroaniline (6.8 g, 97.84%). ES MS M/Z = 193.1 [M+H] ⁺ . [00318] Step 2: To a solution of N-cyclobutyl-2-nitroaniline (6.8 g, 35.4 mmol) in methanol (25 mL) 10% Pd/C (0.1 g, 0.940 mmol) was added and the mixture was stirred at ambient temperature under a hydrogen balloon for 3 h. After completion of the reaction, reaction mixture was filtered through celite bed and washed with methanol. The organic layer was filtered and concentrated under reduced pressure to provide the crude product (5.6 g, 98%). ES MS M/Z = 163.3 [M+1] ⁺ . [00319] Step 3: To a stirred solution of N1-cyclobutylbenzene-1,2-diamine (1.6 g, 9.86 mmol) in dry DMF (24 mL), and pyridine (2.38 mL, 29.6 mmol) was added and dichloro-1λ⁴,2,3-dithiazol-1-ylium chloride (2.26 g, 10.8 mmol) and the mixture was stirred at ambient temperature for 16 h. The crude was diluted with ethyl acetate, washed with water and brine, dried over sodium sulfate, filtered, and concentrated. The crude was purified by flash column chromatography to afford 1-cyclobutyl-1H-1,3- benzodiazole-2-carbonitrile (0.570 g, 29% ). ES MS M/Z = 198.1 [M+H] ⁺ . [00320] Step 4 & 5: To a stirred solution of 1-cyclobutyl-1H-1,3-benzodiazole-2-carbonitrile (1.2 g, 6.08 mmol) in methanol (10 mL) and water (6 mL) was added disodium carbonate (0.387 g, 3.65 mmol) and hydrogen N-methylhydroxylamine chloride (0.610 g, 7.3 mmol) and the mixture was stirred at ambient temperature for 2 h. At this time 1,4-dimethyl but-2-ynedioate (0.963 mL, 7.86 mmol) was added and the mixture was stirred at ambient temperature for 5 h. After completion, the reaction mixture was concentrated under reduced pressure to provide the crude product which was diluted with ethyl acetate, washed with water and brine, dried over sodium sulfate, filtered, and concentrated. The crude was purified by flash column chromatography to afford methyl 3-(1-cyclobutyl-1H-1,3-benzodiazol-2- yl)-5-(2-methoxy-2-oxoethyl)-2-methyl-2,5-dihydro-1,2,4-oxad iazole-5-carboxylate (1.4 g, 59%) as a yellow liquid. ES MS M/Z = 387.2 [M+H] ⁺ . [00321] Step 6: To a solution of methyl 3-(1-cyclobutyl-1H-1,3-benzodiazol-2-yl)-5-(2-methoxy-2- oxoethyl)-2-methyl-2,5-dihydro-1,2,4-oxadiazole-5-carboxylat e (1.4 g, 3.62 mmol) in 1,4-xylene (10 mL) was added and the mixture was stirred at 145 °C for 10 h. After completion, the reaction mixture was concentrated to provide the crude product which washed with pentane (5X) and dried under reduced pressure to provide the crude product (0.85 g, 66%). ES MS M/Z = 355.0 [M+H] ⁺ . [00322] Step 7: To a stirred solution of methyl 2-(1-cyclobutyl-1H-1,3-benzodiazol-2-yl)-5-hydroxy-1- methyl-6-oxo-1,6-dihydropyrimidine-4-carboxylate (0.750 g, 2.12 mmol) in THF (5 mL), methanol (5 mL) and sodium hydroxide (0.254 g, 6.35 mmol) in water (5 mL) was added at ambient temperature. The reaction mixture was heated to 50 °C for 3 h. The reaction mixture was concentrated and acidified with 1N HCl (pH ~ 2), then extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to provide crude 2-(1- cyclobutyl-1H-1,3-benzodiazol-2-yl)-5-hydroxy-1-methyl-6-oxo -1,6-dihydropyrimidine-4-carboxylic acid (0.570 g, 79% ) as a solid. ES MS M/Z = 341.0 [M+H] ⁺ . [00323] Step 8: To a stirred solution of 2-(1-cyclobutyl-1H-1,3-benzodiazol-2-yl)-5-hydroxy-1-methyl- 6-oxo-1,6-dihydropyrimidine-4-carboxylic acid (0.150 g, 0.441 mmol) in DMF (1 mL), HATU (0.335 g, 0.881 mmol), DIPEA (0.11 mL, 0.661 mmol) and 2-aminophenol (0.062 g, 0.573 mmol) was added and the mixture was stirred at 100 °C for 24 h. After completion, the reaction mixture was diluted with ethyl acetate, washed with water and brine, dried over sodium sulfate, filtered, and concentrated. The crude was purified by preparative-TLC (70% EtOAc in Hexane) (0.07 g, 36%). ES MS M/Z = 432.1 [M+H] ⁺ . [00324] Step 9: To a solution of 2-(1-cyclobutyl-1H-1,3-benzodiazol-2-yl)-5-hydroxy-N-(2- hydroxyphenyl)-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carbox amide (0.050 g, 0.116 mmol) in 1,4- xylene (1 mL) was added 4-methylbenzene-1-sulfonic acid (0.025 mg, 0.145 mmol) and the mixture was refluxed for 3 h. After completion, the reaction mixture was concentrated under the reduced pressure. The crude was basified with 1N NaOH (pH ~ 9) then reaction mixture was diluted with DCM, washed with water and brine, dried over sodium sulfate, filtered, and concentrated. The crude compound was purified by preparative HPLC to afford 6-(1,3-benzoxazol-2-yl)-2-(1-cyclobutyl-1H-1,3-benzodiazol-2 - yl)-5-hydroxy-3-methyl-3,4-dihydropyrimidin-4-one (0.0025 g, 4%). ES MS M/Z = 414.3 [M+H] ⁺ ; ¹ H NMR (400 MHz, DMSO-d6) δ ppm; 11.49 (bs, 1 H), 7.86 (d, J = 8 Hz, 2 H), 7.77 (d, J = 8 Hz, 2 H), 7.35 - 7.48 (m, 4 H), 6.9 - 7.20 (m, 1 H), 5.16 (m, 1 H), 3.49 (s, 3 H), 2.67 (m, 2 H), 2.33 (m, 2 H), 1.76 - 1.86 (m, 2 H). Example 12: 6-(1,3-Benzoxazol-2-yl)-5-hydroxy-3-methyl-2-[methyl({phenyl [3-(1H-1,2,3,4-tetrazol- 5-yl)phenyl]methyl})amino]-3,4-dihydropyrimidin-4-one

[00325] Step 1: To a stirred solution of methyl 2-chloro-5-methoxy-1-methyl-6-oxo-1,6- dihydropyrimidine-4-carboxylate (2.5 g, 10.7 mmol) in DMSO (15.00 mL), 1-(3-bromophenyl)-1- phenylmethanamine (2.82 g, 10.7 mmol) and DIPEA (1.88 mL, 10.7 mmol) were added and the reaction mixture was stirred at 110°C for 6 h. After completion of the reaction, the mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain crude product which was purified by flash chromatography. The desired fractions were concentrated to provide methyl 2-{[(3-bromophenyl)(phenyl)methyl]amino}-5-methoxy-1-methyl- 6-oxo-1,6-dihydropyrimidine-4-carboxylate (3.0 g, 60%). [00326] Step 2: To a stirred solution of methyl 2-[(diphenylmethyl)amino]-5-methoxy-1-methyl-6-oxo- 1,6-dihydropyrimidine-4-carboxylate (3 g, 6.55 mmol) in THF (15 mL) and water (6 mL), lithium hydroxide (0.78 g, 5 eq., 32.7 mmol) was added at ambient temperature. The reaction mixture was allowed to stir at ambient temperature for 16 h. After completion, the reaction mixture was concentrated. The residue was diluted with water and washed by ethyl acetate. The aqueous layer was acidified with 2 N HCl solution and extracted with 10% methanol in DCM. The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated to provide 2-[(diphenylmethyl)amino]-5-methoxy-1- methyl-6-oxo-1,6-dihydropyrimidine-4-carboxylic acid (2.8 g, 95%). [00327] Step 3: To a solution of 2-{[(3-bromophenyl)(phenyl)methyl]amino}-5-methoxy-1-methyl- 6- oxo-1,6-dihydropyrimidine-4-carboxylic acid (2.8 g, 6.3 mmol) and iodoaniline (1.66 g, 7.56 mmol) in DMF (20 mL), was added DIPEA (3.3 mL, 3 eq., 18.9 mmol) and HATU (3.60 g, 1.5 eq., 9.45 mmol) and the mixture was stirred at ambient temperature for 16 h. After completion, the reaction mixture was quenched with water and extracted with ethyl acetate. The combined organic layers were concentrated under vacuum to obtain crude product which was purified by flash chromatography. The desired fractions were concentrated to afford 2-{[(3-bromophenyl)(phenyl)methyl]amino}-N-(2-iodophenyl)-5- methoxy-1-methyl-6-oxo-1,6 dihydropyrimidine-4-carboxamide (3.5 g, 84%). [00328] Step 4: To a stirred solution of 2-{[(3-bromophenyl)(phenyl)methyl]amino}-N-(2- iodophenyl)-5-methoxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4 -carboxamide (3.5 g, 5.42 mmol) in toluene (15.00 mL), was added potassium carbonate (2.25 g, 3 eq., 16.3 mmol) and then methyl[2- (methylamino)ethyl]amine (584 µL, 5.42 mmol) was added for 20 min. Copper iodide (344 mg, 0.2 eq., 1.08 mmol) was then added and the mixture was stirred at 100°C for 16 h. After completion, the reaction mixture was concentrated under reduced pressure and the residue was diluted with water and extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated to obtain crude product which was purified by flash chromatography. The desired fractions were concentrated to provide 6-(1,3-benzoxazol-2-yl)-2-{[(3-bromophenyl)(phenyl)methyl]am ino}-5- methoxy-3-methyl-3,4-dihydropyrimidin-4-one (1.5 g, 5.42 mmol, 36%). [00329] Step 5: To a stirred solution of 6-(1,3-benzoxazol-2-yl)-2-{[(3- bromophenyl)(phenyl)methyl]amino}-5-methoxy-3-methyl-3,4-dih ydropyrimidin-4-one (1.5 g, 2.9 mmol) in DMF (5 mL) sodium hydride (174 mg, 1.5 eq., 4.35 mmol) and iodomethane (217 µL, 1.2 eq., 3.48 mmol) were added at 0°C. The mixture was stirred at ambient temperature for 2 h. After completion, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and then concentrated to obtain crude product which was purified by flash chromatography. The desired fractions were concentrated to provide 6-(1,3-benzoxazol- 2-yl)-2-{[(3-bromophenyl)(phenyl)methyl](methyl)amino}-5-met hoxy-3-methyl-3,4-dihydropyrimidin- 4-one (0.50 g, 19%). [00330] Step 6: To a stirred solution of 6-(1,3-benzoxazol-2-yl)-2-{[(3- bromophenyl)(phenyl)methyl](methyl)amino}-5-methoxy-3-methyl -3,4-dihydropyrimidin-4-one (0.50 g, 941 µmol) in DMF (5.00 mL), zinc cyanide (0.16 g, 1.5 eq., 1.41 mmol) and the mixture was degassed. After degassing, 1,1′-bis(diphenylphosphino)ferrocene (0.10 mg, 0.1 eq., 188 µmol) and tris(dibenzylideneacetone)dipalladium (0.08 mg, 0.1 eq., 94.1 µmol) was added and then reaction mixture was stirred at 120°C for 16 h. After completion of the reaction, the mixture was diluted with water and extracted with ethyl acetate. The organic layer dried over anhydrous sodium sulfate, filtered, and concentrated to obtain crude product which was purified by flash chromatography. The desired fractions were concentrated under reduce pressure to provide 3-({[4-(1,3-benzoxazol-2-yl)-5-methoxy-1- methyl-6-oxo-1,6-dihydropyrimidin -2-yl](methyl)amino}(phenyl)methyl)benzonitrile (0.40 g, 796 µmol) as brownish solid (0.40 g, 85%). [00331] Step 7: To a stirred solution of 3-({[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2-yl](methyl)amino}(phenyl)methyl)benzonitr ile (0.40 g, 838 µmol) in DMF (5 mL), ammonium chloride (0.22 mg, 5 eq., 4.19 mmol) and sodium azide (0.27 mg, 5 eq., 4.19 mmol) were added and the mixture was stirred at 120 °C for 16 h. After completion, the reaction mixture was cooled to ambient temperature and 1N HCl solution was added. A solid was obtained and which was filtered and dried under reduced pressure to provide 6-(1,3-benzoxazol-2-yl)-5-methoxy-3-methyl-2- [methyl({phenyl[3-(1H-1,2,3,4-tetrazol-5-yl)phenyl]methyl})a mino]-3,4-dihydropyrimidin-4-one (0.30 g, 39%). [00332] Step 8: To a stirred solution of 6-(1,3-benzoxazol-2-yl)-5-methoxy-3-methyl-2- [methyl({phenyl[3-(1H-1,2,3,4-tetrazol-5-yl)phenyl]methyl})a mino]-3,4-dihydropyrimidin-4-one (0.1 g, 192 µmol) in DMF (1 mL), lithium bromide (83.4 mg, 5 eq., 961 µmol) was added and the mixture was stirred at 100 °C for 16 h. After completion, the reaction mixture was concentrated under reduced pressured to provide a residue which was dissolved with water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain crude product which was purified by reverse phase HPLC to obtain 6-(1,3-benzoxazol-2-yl)-5-hydroxy-3-methyl-2- [methyl({phenyl[3-(1H-1,2,3,4-tetrazol-5-yl)phenyl]methyl})a mino]-3,4-dihydropyrimidin-4-one (0.01 g, 10%). ES MS M/Z = 507.30 [M+H] ⁺ ; ¹ H NMR (400 MHz, DMSO-d6) δ 16.87 (bs s, 1H), 10.54 (s, 1H), 8.18 (s, 1H), 7.83-7.71 (m, 3H), 7.66 (d, J = 7.6 Hz, 1H), 7.54 (d, J = 8 Hz, 2H), 7.45 (m, J = 3H), 7.31 (t, J = 12 Hz, 2H), 7.20 (t, J = 12, 1H), 5.83 (s, 1H), 3.69 (s, 3H), 2.60 (s, 3H). Example 13: 6-(benzo[d]oxazol-2-yl)-5-hydroxy-3-methyl-2-(methylamino)py rimidin-4(3H)-one [00333] Step 1: To a stirred solution of 2-chloro-5-methoxy-6-oxo-1,6-dihydropyrimidine-4-carboxylic acid (20 g, 97.8 mmol) in DMF (260.0 mL), dipotassium carbonate (40.5 g, 3 eq., 293 mmol) and iodomethane (12.8 mL, 2.1 eq., 205 mmol) were added and the reaction mixture was stirred at ambient temperature for 16 h . After completion of the reaction, the mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain crude product which was purified by flash chromatography. The desired fractions were concentrated to afford methyl 2-chloro-5-methoxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-ca rboxylate (12.0 g, 52%). [00334] Step 2: To a stirred solution of methyl 5-methoxy-1-methyl-2-(methylamino)-6-oxo-1,6- dihydropyrimidine-4-carboxylate (1 g, 4.4 mmol) and 2-aminophenol (480 mg, 4.4 mmol) in toluene (10 mL) was added triethylamine (675 µL, 1.1 eq., 4.84 mmol) and the mixture was cooled to 0 °C. Trimethylalumane (635 mg, 2 eq., 8.8 mmol) was added and the mixture was stirred at 80 °C for 1 h in the microwave. After completion, the reaction mixture was quenched with a saturated solution of NH ₄ Cl solution and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to afford crude product which was purified by flash chromatography to provide N-(2-hydroxyphenyl)-5-methoxy-1-methyl-2-(methylamino)-6-oxo -1,6-dihydropyrimidine-4- carboxamide (0.20 g, 14%). [00335] Step 3: A stirred solution of N-(2-hydroxyphenyl)-5-methoxy-1-methyl-2-(methylamino)-6- oxo-1,6-dihydropyrimidine-4-carboxamide (0.2 g, 657 µmol) in acetic acid (2.0 mL) was irradiated at 180 °C for 2 h in microwave. After completion, the reaction mixture was quenched with a saturated solution of sodium bicarbonate and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to afford crude product which was purified by flash chromatography. The desired fractions were concentrated to provide 6-(1,3-benzoxazol-2-yl)-5-methoxy- 3-methyl-2-(methylamino)-3,4-dihydropyrimidin-4-one (0.14 g, 58%). [00336] Step 4: To a solution of 6-(1,3-benzoxazol-2-yl)-5-methoxy-3-methyl-2-(methylamino)-3 ,4- dihydropyrimidin-4-one (140 mg, 489 µmol) in DMF (5.0 mL) was added lithium bromide (212 mg, 5 eq., 2.45 mmol) and the mixture was stirred for 16 h at 100 °C. After completion, the reaction was cooled to ambient temperature, concentrated, diluted with water, and extracted with 10% methanol in DCM. The crude was purified by reverse phase HPLC and the desired fractions were lyophilized to afford 6-(1,3- benzoxazol-2-yl)-5-hydroxy-3-methyl-2-(methylamino)-3,4-dihy dropyrimidin-4-one (0.025 g,18.59%). ES MS M/Z = 273.15 [M+H] ⁺ ; ¹ H NMR (400 MHz, DMSO-d6) δ 9.97 (s, 1H), 7.89-7.85 (m, 2H), 7.51- 7.44 (m, 2H), 6.87 (m, 1H), 3.36 (s, 3H), 2.90 (d, J = 4.4 Hz, 3H). Example 14: 2-(benzhydryl(methyl)amino)-6-(benzo[d]thiazol-2-yl)-5-hydro xy-3-methylpyrimidin- 4(3H)-one [00337] Step 1: To a solution of 2-[(diphenylmethyl)(methyl)amino]-5-methoxy-1-methyl-6-oxo-1 ,6- dihydropyrimidine-4-carbaldehyde (0.2 g, 550 µmol) and benzene-1,2-diamine (71.4 mg, 1.2 eq., 660 µmol) was added in DMSO (9.61 mL, 134 mmol), disodium sulfinatosulfonate (126 mg, 1.2 eq., 660 µmol) and the solution was stirred at 110°C for 16 h. After completion, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain crude product which was purified by flash chromatography to afford 6-(1H-1,3-benzodiazol-2-yl)-2-[(diphenylmethyl)(methyl)amino ]-5-methoxy-3-methyl-3,4- dihydropyrimidin-4-one (0.160 g, 49%) [00338] Step 2: To a solution of 6-(1H-1,3-benzodiazol-2-yl)-2-[(diphenylmethyl)(methyl)amino ]-5- methoxy-3-methyl-3,4-dihydropyrimidin-4-one (0.2 g, 443 µmol) in DMF (10 mL, 129 mmol) was added lithium bromide (192 mg, 5 eq., 2.21 mmol) and the mixture was stirred for 16 h at 100 °C. After completion of the reaction, the mixture was concentrated and then ice cold water was added to obtain solid (crude) which was purified by reverse phase HPLC. The desired fractions were lyophilized to afford 6-(1H-1,3-benzodiazol-2-yl)-2-[(diphenylmethyl)(methyl)amino ]-5-hydroxy-3-methyl-3,4- dihydropyrimidin-4-one. (0.009 g, 4%). ES MS M/Z=438.20 [M+H] ⁺ ; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.61 (bs, 1H), 8.18-8.16 (d, J = 8.0 Hz, 1H), 8.08-8.06 (d, J = 8.0 Hz, H), 7.58-7.54 (t, J = 16.0 Hz, 6H), 7.50-7.47 (t, J = 12.0 Hz, 4H), 7.28-7.24 (t, J = 16.0 Hz, 2H), 5.67 (s, 1H), 3.68 (s, 3H), 2.55 (s, 3H).1.14 (s, 1H). Example 15: 6-(1,3-benzoxazol-2-yl)-2-[(diphenylmethyl)(methyl)amino]-5- hydroxy-3-methyl-3,4- dihydropyrimidin-4-one [00339] Step 1: To a solution of 2-[(diphenylmethyl)amino]-5-methoxy-1-methyl-6-oxo-1,6- dihydropyrimidine-4-carboxylic acid (1.0 g, 2.74 mmol) in toluene (10 mL, 84.5 mmol) & 2- aminophenol (0.299 g, 2.74 mmol), DIPEA (956 µL, 2 eq., 5.47 mmol) and tripropyl-1,3,5,2λ⁵,4λ⁵,6λ⁵- trioxatriphosphinane-2,4,6-trione (5.22 g, 3 eq., 8.21 mmol) was added and the solution was heated in the microwave at 190°C for 1 h. Upon completion, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer dried over anhydrous sodium sulfate, filtered, and concentrated to obtain crude product which was purified by flash chromatography and the desired fractions were concentrated to obtain 6-(1,3-benzoxazol-2-yl)-2-[(diphenylmethyl)amino]-5-methoxy- 3-methyl-3,4- dihydropyrimidin-4-one (0.320 g, 13%). [00340] Step 2: To a solution of 6-(1,3-benzoxazol-2-yl)-2-[(diphenylmethyl)amino]-5-methoxy- 3- methyl-3,4-dihydropyrimidin-4-one (190 mg, 433 µmol) in DMF (2 mL) was added lithium bromide (54.4 µL, 5 eq., 2.17 mmol) and the mixture was stirred for 2 days at 100 °C. Upon completion of the reaction, it was concentrated, water was added, and the obtained solid was filtered and dried to provide crude product which was purified by reverse phase HPLC and the desired fractions were lyophilized to provide 6-(1,3-benzoxazol-2-yl)-2-[(diphenylmethyl)amino]-5-hydroxy- 3-methyl-3,4-dihydropyrimidin- 4-one (8 mg, 4%). ES MS M/Z = 425 [M+H] ⁺ , ¹ H NMR (400 MHz, DMSO-d6) δ 9.98 (s, 1H), 7.86 (d, J = 7.6 Hz, 2H), 7.49-7.44 (m, 7H), 7.35 (t, J = 7.6 Hz, 4H), 7.25 (t, J = 7.2 Hz, 2H), 6.55 (d, J = 7.6 Hz, 1H), 3.53 (s, 3H). Example 16: 6-(1,3-benzoxazol-2-yl)-2-[(diphenylmethyl)(methyl)amino]-5- hydroxy-3-methyl-3,4- dihydropyrimidin-4-one

[00341] Step 1: To a stirred solution of methyl 2-chloro-5-methoxy-1-methyl-6-oxo-1,6- dihydropyrimidine-4-carboxylate (5.9 g, 25.3 mmol) in DMSO (15 mL) and (diphenylmethyl)(methyl)amine (5.0 g, 25.3 mmol), DIPEA (4.43 mL, 25.3 mmol) was added and the solution was stirred at 110 °C for 6 h. Upon completion, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer dried over anhydrous sodium sulfate, filtered, and concentrated to obtain crude product which was purified by flash chromatography and the desired fractions were concentrated to provide methyl 2-[(diphenylmethyl)(methyl)amino]-5-methoxy-1-methyl- 6-oxo-1,6-dihydropyrimidine-4-carboxylate (3.8 g, 32%). [00342] Step 2: To a stirred solution of methyl 2-[(diphenylmethyl)(methyl)amino]-5-methoxy-1- methyl-6-oxo-1,6-dihydropyrimidine-4-carboxylate (0.8 g, 2.03 mmol) in THF (2 ml, 24.6 mmol) and water (0.5 mL), lithium hydroxide (0.417 g, 5 eq., 10.2 mmol) was added and the mixture was stirred at ambient temperature for 16 h. Upon completion, the reaction mixture was diluted with aqueous 6 N HCl and extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated to afford 2-[(diphenylmethyl)(methyl)amino]-5-methoxy-1-methyl-6-oxo-1 ,6- dihydropyrimidine-4-carboxylic acid (0.580 g, 1.36 mmol) as sticky brown solid (0.580 g, 66%). [00343] Step 3: To a stirred solution of 2-[(diphenylmethyl)(methyl)amino]-5-methoxy-1-methyl-6- oxo-1,6-dihydropyrimidine-4-carboxylic acid (0.5 g, 1.32 mmol) in DMF (2.59 mL, 33.4 mmol) and 2- iodoaniline (0.346 g, 1.2 eq., 1.58 mmol) was added DIPEA (689 µL, 3 eq., 3.95 mmol) and HATU (0.752 g, 1.5 eq., 1.98 mmol) and the mixture was stirred at ambient temperature for 16 h. Upon completion of the reaction, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain crude product which was purified by flash chromatography and the desired fractions were concentrated to afford 2-[(diphenylmethyl)(methyl)amino]-N-(2-iodophenyl)-5-methoxy -1-methyl-6-oxo-1,6- dihydropyrimidine-4-carboxamide (0.320 mg, 38%). [00344] Step 4: To a solution of 2-[(diphenylmethyl)(methyl)amino]-N-(2-iodophenyl)-5-methoxy -1- methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide (0.320 g, 551 µmol) in acetonitrile (3 mL) was added cesium carbonate (0.269 g, 1.5 eq., 827 µmol) and the mixture was stirred at ambient temperature and the reaction mixture was degassed with nitrogen for 5 min. Iodocopper (5.25 mg, 0.05 eq., 27.6 µmol) and 1,10-phenanthroline (9.9 mg, 0.1 eq., 55.1 µmol) were added and degassing continued for 5 min. The mixture was heated at 110 °C for 16 h. Upon completion of the reaction, water was added and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain crude product which was purified by flash chromatography to afford 6-(1,3-benzoxazol-2-yl)-2-[(diphenylmethyl)(methyl)amino]-5- methoxy-3-methyl-3,4-dihydropyrimidin- 4-one (0.050 g, 17%). [00345] Step 5: To a solution of 6-(1,3-benzoxazol-2-yl)-2-[(diphenylmethyl)(methyl)amino]-5- methoxy-3-methyl-3,4-dihydropyrimidin-4-one (0.050 mg, 110 µmol) in DMF (2 mL) was added lithium bromide (13.9 µL, 5 eq., 552 µmol) and the mixture was stirred for 16 h at 100 °C. Upon completion the reaction mixture was concentrated, water was added, and the obtained solid was filtered and dried to provide crude product which was purified by reverse phase HPLC. The desired fractions were lyophilized to provide 6-(1,3-benzoxazol-2-yl)-2-[(diphenylmethyl)(methyl)amino]-5- hydroxy-3-methyl- 3,4-dihydropyrimidin-4-one (1.5 mg, 3.0%). ES MS M/Z= 440 [M+H] ⁺ ; ¹ H NMR (400 MHz, DMSO-d6) δ 10.54 (s, 1H), 7.85 (d, J = 7.2 Hz, 2H), 7.46 (d, J = 7.6 Hz, 6H), 7.27 (t, J = 7.2 Hz, 4H), 7.15 (t, J = 7.2 Hz, 2H), 5.71 (s, 1H), 3.66 (s, 3H), 2.56 (s, 3H). Example 17: 2-[(diphenylmethyl)(methyl)amino]-5-hydroxy-3-methyl-6-(1-me thyl-1H-1,3- benzodiazol-2-yl)-3,4-dihydropyrimidin-4-one [00346] Step 1: To a solution of methyl 2-chloro-5-methoxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4- carboxylate (5.9 g, 25.3 mmol) in DMSO (15 mL) (diphenylmethyl)(methyl)amine (5.0 g, 25.3 mmol) and DIPEA (4.43 mL, 25.3 mmol) were added and the solution was stirred at 110 °C for 6 h. Upon completion of the reaction, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer dried over anhydrous sodium sulfate, filtered, and concentrated to obtain crude product which was purified by flash chromatography and desired fractions were concentrated to provide methyl 2-[(diphenylmethyl)(methyl)amino]-5-methoxy-1-methyl-6-oxo-1 ,6-dihydropyrimidine-4-carboxylate (3.8 g, 32%). [00347] Step 2: To a stirred solution of methyl 2-[(diphenylmethyl)amino]-5-methoxy-1-methyl-6-oxo- 1,6-dihydropyrimidine-4-carboxylate (2.0 g, 1 eq., 5.27 mmol) in THF (30 mL, 369 mmol), sodium borane (0.936 g, 5 eq., 25.4 mmol) was added and reaction mixture was heated at 65 °C for 15 min then methanol (8 mL, 197 mmol) was added drop-wise and the reaction mixture heated at 65 °C for 4h. Upon completion of the reaction, the reaction mixture was quenched with a saturated solution of ammonium chloride and extracted with ethyl acetate. The combined organic layers were collected, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to provide the crude product which was purified by flash chromatography and desired fractions were concentrated to afford 2- [(diphenylmethyl)amino]-6-(hydroxymethyl)-5-methoxy-3-methyl -3,4-dihydropyrimidin-4-one (1.6g, 70%). [00348] Step 3: To a stirred solution of 2-[(diphenylmethyl)amino]-6-(hydroxymethyl)-5-methoxy-3- methyl-3,4-dihydropyrimidin-4-one (0.7 g, 1.99 mmol) in toluene (7 mL, 59.2 mmol) dioxomanganese (0.866 g, 5 eq., 9.96 mmol) was added and the mixture was heated at 60 °C for 4 h. Upon completion of the reaction, the reaction mixture passed through celite. The filtrate was concentrated and purified by flash chromatography to afford 2-(benzhydrylamino)-5-methoxy-1-methyl-6-oxo-1,6-dihydropyri midine- 4-carbaldehyde (0.700 g, 50%). [00349] Step 4: To a stirred solution of N1-methylbenzene-1,2-diamine (0.087 g, 716 µmol) and 2- [(diphenylmethyl)amino]-5-methoxy-1-methyl-6-oxo-1,6-dihydro pyrimidine-4-carbaldehyde (0.250 g, 716 µmol) in DMSO (5 mL) disodium sulfinatosulfonate (0.204 g, 1.5 eq., 1.07 mmol) was added and the resultant mixture was heated at 90 °C for 13 h. Upon completion of the reaction, the reaction mixture was diluted with water and extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated. The crude was purified by silica gel column chromatography by using 100-200 silica gel and eluting with 70% ethyl acetate in hexane. The desired fractions were concentrated to afford 2-[(diphenylmethyl)amino]-5-methoxy-3-methyl-6-(1-methyl-1H- 1,3-benzodiazol-2-yl)-3,4-dihydropyrimidin-4-one (240 mg, 70%). [00350] Step 5: To a stirred solution of 2-[(diphenylmethyl)amino]-5-methoxy-3-methyl-6-(1-methyl- 1H-1,3-benzodiazol-2-yl)-3,4-dihydropyrimidin-4-one (0.2 g, 443 µmol) in DMF (1 mL) cesium carbonate (0.130 g, 0.9 eq., 399 µmol) & iodomethane (24.8 µL, 0.9 eq., 399 µmol) were added to the solution it was stirred at ambient temperature for 16 h. Upon completion of the reaction, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain crude product which was purified by flash chromatography and desired fractions were concentrated to provide 2-[(diphenylmethyl)(methyl)amino]- 5-methoxy-3-methyl-6-(1-methyl-1H-1,3-benzodiazol-2-yl)-3,4- dihydropyrimidin-4-one (0.150 g, 72%). [00351] Step 6: To a solution of 2-[(diphenylmethyl)(methyl)amino]-5-methoxy-3-methyl-6-(1-me thyl- 1H-1,3-benzodiazol-2-yl)-3,4-dihydropyrimidin-4-one (0.450 g, 967 µmol) in DMF (3 mL) was added lithium bromide (121 µL, 5 eq., 4.83 mmol) and the mixture was stirred for 16 h at 100 °C . Upon completion of the reaction, the reaction mixture was concentrated and water was added. The obtained solid was filtered and dried to provide crude product which was purified by reverse phase HPLC to provide 2-[(diphenylmethyl)(methyl)amino]-5-hydroxy-3-methyl-6-(1-me thyl-1H-1,3-benzodiazol-2-yl)- 3,4-dihydropyrimidin-4-one (106 mg, 24%). ES MS M/Z= 452.3 [M+H] ⁺ , ¹ H NMR (400 MHz, DMSO- d6) δ 13.31 (s, 1H), 7.74-7.69 (m, 2H), 7.43-7.28 (m, 10H), 7.19 (t, J = 7.2 Hz, 2H), 5.71 (s, 1H), 4.13 (s, 3H), 3.69 (s, 3H), 2.53 (s, 3H). Example 18: 6-(1H-1,3-benzodiazol-2-yl)-2-[(diphenylmethyl)(methyl)amino ]-5-hydroxy-3-methyl- 3,4-dihydropyrimidin-4-one [00352] Step 1: To a stirred solution of 2-[(diphenylmethyl)(methyl)amino]-5-methoxy-1-methyl-6- oxo-1,6-dihydropyrimidine-4-carbaldehyde (0.2 g, 550 µmol) and benzene-1,2-diamine (71.4 mg, 1.2 eq., 660 µmol) was added DMSO (9.61 mL, 134 mmol) and disodium sulfinatosulfonate (126 mg, 1.2 eq., 660 µmol) and the solution was stirred at 110°C for 16 h. After completion of the reaction, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain crude product which was purified by flash chromatography. The desired fractions were concentrated to provide 6-(1H-1,3-benzodiazol-2-yl)- 2-[(diphenylmethyl)(methyl)amino]-5-methoxy-3-methyl-3,4-dih ydropyrimidin-4-one (0.160 g, 49%) [00353] Step 2: To a solution of 6-(1H-1,3-benzodiazol-2-yl)-2-[(diphenylmethyl)(methyl)amino ]-5- methoxy-3-methyl-3,4-dihydropyrimidin-4-one (0.2 g, 443 µmol) in DMF (10 mL, 129 mmol) was added lithium bromide (192 mg, 5 eq., 2.21 mmol) and the mixture was stirred for 16 h at 100 °C. After completion, the reaction was cooled to ambient temperature, concentrated, and diluted with water. The obtained solid was filtered, dried, and purified by reverse phase HPLC to afford 6-(1H-1,3-benzodiazol- 2-yl)-2-[(diphenylmethyl)(methyl)amino]-5-hydroxy-3-methyl-3 ,4-dihydropyrimidin-4-one. (0.009 g, 4%). ES MS M/Z=438.20 [M+H]+); ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 12.85 (bs, 1H), 12.17 (bs, 1H), 7.73-7.70 (t, J = 12.0 Hz, 2H), 7.52-7.50 (d, J = 8.0 Hz, 4H), 7.32 (s, 2H), 7.25-7.22 (t, J = 12.0 Hz, 4H), 7.13-7.09 (t, J = 16.0 Hz, 2H), 5.84 (s, 1H), 3.75 (s, 3H), 2.50 (s, 3H). [00354] The following compounds were synthesized in a similar manner: Example 19: Synthesis of 2-(((4-(1H-tetrazol-5-yl)phenyl)(phenyl)methyl)(methyl)amino )-6- (benzo[d]oxazol-2-yl)-5-hydroxy-3-methylpyrimidin-4(3H)-one [00355] ES MS M/Z=507.30 [M+H] ⁺ ; NMR (400 MHz, DMSO-d ₆ ) δ 16.74 (br s, 1H), 10.56 (s, 1H), 7.93 (d, J = 8.00 Hz, 2H), 7.86 (t, J = 7.60 Hz, 2H), 7.71 (d, J = 8.40 Hz, 2H), 7.54-7.43 (m, 4H), 7.31 (t, J = 7.20 Hz, 2H), 7.20 (t, J = 7.60 Hz, 1H), 5.83 (s, 1H), 3.71 (s, 3H), 2.61 (s, 3H). Example 20: 5-hydroxy-3-methyl-6-(oxazolo[5,4-c]pyridin-2-yl)-2-(1-pheny l-3,4- dihydroisoquinolin-2(1H)-yl)pyrimidin-4(3H)-one _[00356] ES MS M/Z=452.2 [M+H] ⁺ ; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.92 (bs, 1H), 9.13 (s, 1H), 8.51 (d, J =5.2 Hz, 1H), 7.84 (d, J =4.8 Hz, 1H), 7.26-7.07 (m, 8H), 6.82 (d, J =8.0 Hz, 1H), 5.97 (s, 1H), 3.53-3.47 (m, 4H), 3.22-3.16 (m, 2H), 2.96-2.92 (m, 2H) Example 21: 6-(1,3-benzoxazol-2-yl)-2-{[(4-chlorophenyl) (phenyl)methyl] (methyl)amino}-5- hydroxy-3-methyl-3,4-dihydropyrimidin-4-one [00357] ES MS M/Z =473.2 [M+H] ⁺ ; ¹ H NMR (400 MHz, DMSO-d6) δ ppm: 10.56 (s, 1 H), 7.87 (m, 2 H), 7.48 (m, 6 H), 7.33 (m, 4 H), 7.19 (m, 1 H), 5.76 (s, 1 H), 3.67 (s, 3 H), 2.57 (s, 3 H). Example 22: 6-(1,3-benzoxazol-2-yl)-2-{[(3-chlorophenyl)(phenyl)methyl]( methyl)amino}-5- hydroxy-3-methyl-3,4-dihydropyrimidin-4-one _[00358] ES MS M/Z = 473.2 [M+H] ⁺ ; UPLC: 99.1%; ¹ H NMR (400 MHz, DMSO-d ₆ ) 10.59 (s , 1 H ) , 7.85 - 7.83(d, J =8 Hz , 2 H), 7.58-7.43 (m, 6 H), 7.33-7.27 (m, 3 H), 7.21-7.20 (m, 2 H), 5.7 (s, 1 H), 3.70 (s, 3 H), 2.58(s, 3 H). Example 23: 3-(((4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6-di hydropyrimidin-2- yl)(methyl)amino)(phenyl)methyl)benzamide [00359] ES MS M/Z =482.3 [M+H] ⁺ ; ¹ H NMR (400 MHz, DMSO-d6) δ ppm: 7.96-8.01(m, 1H), 7.84 (s, 3H), 7.66 (m, 2H), 7.66 (m, 2 H), 7.5 (m, 3H), 7.30 (m, 4H), 7.18 (m, 1H), 5.77 (s, 1H), 3.69 (s, 3H), 2.58 (s, 3H). Example 24: 4-(((4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6-di hydropyrimidin-2- yl)(methyl)amino)(phenyl)methyl)benzonitrile [00360] ES MS M/Z=464.25 [M+H] ⁺ ; ¹ H, NMR (400 MHz, DMSO-d6) δ 10.75 (br s, 1H), 7.84-7.82 (m, 2H), 7.74-7.68 (m, 4H), 7.53 (d, J = 7.20 Hz, 2H), 7.49-7.42 (m, 2H), 7.30 (t, J = 7.60 Hz, 2H), 7.20 (t, J = 7.60 Hz, 2H), 5.81 (s, 1H), 3.68 (s, 3H), 2.57 (s, 3H). Example 25: 3-(((4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6-di hydropyrimidin-2- yl)(methyl)amino)(phenyl)methyl)benzonitrile [00361] ES MS M/Z = 464.25 [M+H] ⁺ ; ¹ H NMR (400 MHz, DMSO-d6) δ 10.51 (bs s, 1H), 8.05 (s, 1H), 7.84 (t, J = 8 Hz, 3H), 7.60-7.44 (m, 6H), 7.31 (t, J = 8 Hz, 2H), 7.20 (t, J = 8 Hz, 16, 1H), 5.80 (s, 1H), 3.69 (s, 3H), 2.59 (s, 3H). Example 26: 6-(benzo[d]oxazol-2-yl)-5-hydroxy-2-(1-phenyl-3,4-dihydroiso quinolin-2(1H)- yl)pyrimidin-4(3H)-one

[00362] Step 1: To stirred solution of methyl 2,6-dichloro-5-methoxypyrimidine-4-carboxylate (5 g, 21.1 mmol) in DMF (5 mL), dipotassium carbonate (3.5 g, 1.2 eq., 25.3 mmol) and phenylmethanol (2.85 mL, 1.3 eq., 27.4 mmol) was added. The resulting mixture was heated to 70 °C for 16 h. After completion, reaction mixture was extracted with ethyl acetate, the organic layer was then dried over anhydrous sodium sulfate and concentrated. The residue was purified by flash chromatography. The desired fractions were concentrated to afford methyl 6-(benzyloxy)-2-chloro-5-methoxypyrimidine-4- carboxylate as liquid (5.0 g, 32%). [00363] Step 2: To a stirred solution of methyl 6-(benzyloxy)-2-chloro-5-methoxypyrimidine-4- carboxylate (0.7 g, 2.27 mmol) in DMSO (5 mL) was added 1-phenyl-1,2,3,4-tetrahydroisoquinoline (475 mg, 2.27 mmol) and DMF (436 µL, 1.1 eq., 2.49 mmol) and the solution was stirred at 110 °C for 16 h. After completion, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulphate, filtered, and concentrated. The residue was purified by flash chromatography. The desired fractions were concentrated to afford methyl 6- (benzyloxy)-5-methoxy-2-(1-phenyl-1,2,3,4-tetrahydroisoquino lin-2-yl) pyrimidine-4-carboxylate as colorless solid (2.5 g, 8.6%). [00364] Step 3: To a stirred solution of methyl 6-(benzyloxy)-5-methoxy-2-(1-phenyl-1,2,3,4- tetrahydroisoquinolin-2-yl) pyrimidine-4-carboxylate (2.5 g, 5.19 mmol) in THF (5.11 mL, 62.7 mmol) and water (0.5 mL), lithium hydroxide (1.06 g, 5 eq., 26 mmol) was added and stirred at ambient temperature for 16 h. After completion, the mixture was diluted with aqueous 6 N HCl and extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulphate, filtered, and concentrated to afford 6-(benzyloxy)-5-methoxy-2-(1-phenyl-1,2,3,4-tetrahydroisoqui nolin-2-yl) pyrimidine-4-carboxylic acid as brown semi-solid. (1.8 g, 22%). [00365] Step 4: To a stirred solution of 6-(benzyloxy)-5-methoxy-2-(1-phenyl-1,2,3,4- tetrahydroisoquinolin-2-yl)pyrimidine-4-carboxylic acid (0.8 g, 1.71 mmol) in THF (6.78 mL) was added 1-(1H-imidazole-1-carbonyl)-1H-imidazole (416 mg, 1.5 eq., 2.57 mmol) and the reaction was stirred at ambient temperature for 30 min. Then 2-aminophenol (205 mg, 1.1 eq., 1.88 mmol) was added and stirred at 60 °C for 16 h. After completion, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated. The crude product was purified by flash chromatography. The desired fractions were concentrated to afford 6- (benzyloxy)-N-(2-hydroxyphenyl)-5-methoxy-2-(1-phenyl-1,2,3, 4-tetrahydroisoquinolin-2- yl)pyrimidine-4-carboxamide (0.7 g, 22%). [00366] Step 5: The solution of 6-(benzyloxy)-N-(2-hydroxyphenyl)-5-methoxy-2-(1-phenyl-1,2, 3,4- tetrahydroisoquinolin-2-yl)pyrimidine-4-carboxamide (350 mg, 627 µmol) in acetic acid (5 mL) was stirred at 140 °C for 4 h. After completion of the reaction, it was concentrated under reduced pressure to afford 6-(1,3-benzoxazol-2-yl)-5-methoxy-2-(1-phenyl-1,2,3,4-tetrah ydroisoquinolin-2-yl)-3,4- dihydropyrimidin-4-one (150 mg, 12%) as an off-colorless solid. [00367] Step 6: To a solution of 2-[4-(1,3-benzoxazol-2-yl)-6-(benzyloxy)-5-methoxy-1,6- dihydropyrimidin-2-yl]-1-phenyl-1,2,3,4-tetrahydroisoquinoli ne (0.2 g, 369 µmol) in DMF (16.9 mL, 219 mmol), lithium bromide (320 mg, 10 eq., 3.69 mmol) was added to the reaction mixture at 0 °C then it was stirred at 80 °C for 16 h. After completion, the reaction mixture was cooled to ambient temperature, concentrated, and diluted with water. The obtained solid was filtered and dried under reduced pressure. The crude was purified by reverse phase HPLC and pure fractions were lyophilized to afford 6-(1,3-benzoxazol-2-yl)-5-hydroxy-2-(1-phenyl-1,2,3,4-tetrah ydroisoquinolin-2-yl)-3,4- dihydropyrimidin-4-one (5 mg, 11.2 µmol) (0.005 g, 3.0%) ES MS M/Z = 437.20 [M+H] ⁺ , NMR (400 MHz, DMSO-d6) δ 12.01 (bs, 1H), 10.18 (bs, 1H ), 7.84 – 7.79 (t, J = 20.0 Hz, 2H), 7.50-7.43 (m, 2H), 7.29 – 7.15 (m, 9H), 6.81 (s, 1H), 4.14 (s, 1H), 3.49 – 3.43 (m, 1H), 3.05-3.03 (m, 1H), 2.82 – 2.77 (m, 1H). [00368] Examples 27, 28, and 29: 6-(benzo[d]oxazol-2-yl)-5-hydroxy-3-methyl-2-(1-phenyl-3,4- dihydroisoquinolin-2(1H)-yl)pyrimidin-4(3H)-one, (R)-6-(benzo[d]oxazol-2-yl)-5-hydroxy-3- methyl-2-(1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl)pyrimidin -4(3H)-one and (S)-6- (benzo[d]oxazol-2-yl)-5-hydroxy-3-methyl-2-(1-phenyl-3,4-dih ydroisoquinolin-2(1H)-yl)pyrimidin- 4(3H)-one

[00369] Step 1: To a stirred solution of methyl 2-chloro-5-methoxy-1-methyl-6-oxo-1,6- dihydropyrimidine-4-carboxylate (2.22 g, 9.56 mmol) in DMSO (20.0 mL) was added 1-phenyl-1,2,3,4- tetrahydroisoquinoline (2 g, 9.56 mmol) and DIPEA (1.84 mL, 1.1 eq., 10.5 mmol) and the solution was stirred at 110°C for 16 h. After completion of the reaction, it was diluted with water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain crude product which was purified by CombiFlash. The desired fractions were concentrated to afford methyl 5-methoxy-1-methyl-6-oxo-2-(1-phenyl-3,4-dihydroisoquinolin- 2(1H)-yl)-1,6- dihydropyrimidine-4-carboxylate (2.5 g, 64%). [00370] Step 2: To a stirred solution of methyl 5-methoxy-1-methyl-6-oxo-2-(1-phenyl-3,4- dihydroisoquinolin-2(1H)-yl)-1,6-dihydropyrimidine-4-carboxy late (2.5 g, 6.17 mmol) in THF (18.0 mL) and water (6.0 mL) was added lithium hydroxide (738 mg, 5 eq., 30.8 mmol) and the mixture was stirred at ambient temperature for 16 h. After completion, the reaction mixture was acidified with HCl and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 5-methoxy-1-methyl-6-oxo-2-(1-phenyl-3,4-dihydroisoquinolin- 2(1H)-yl)-1,6- dihydropyrimidine-4-carboxylic acid (2.2 g, 91%). [00371] Step 3: To a stirred solution of 5-methoxy-1-methyl-6-oxo-2-(1-phenyl-3,4- dihydroisoquinolin-2(1H)-yl)-1,6-dihydropyrimidine-4-carboxy lic acid (2.47 g, 6.31 mmol) in THF (25.0 mL) was added 1-(1H-imidazole-1-carbonyl)-1H-imidazole (1.53 g, 1.5 eq., 9.47 mmol) and the reaction was stirred at ambient temperature for 30 minutes then 2-aminophenol (757 mg, 1.1 eq., 6.94 mmol) was added and reaction was stirred for 16 h at 60 °C. After completion, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated to provide crude product which was purified by CombiFlash. The desired fractions were concentrated to afford N-(2-hydroxyphenyl)-5-methoxy-1-methyl-6-oxo-2-(1-phenyl-3,4 - dihydroisoquinolin-2(1H)-yl)-1,6-dihydropyrimidine-4-carboxa mide (2.3 g, 69%). [00372] Step 4: A solution of N-(2-hydroxyphenyl)-5-methoxy-1-methyl-6-oxo-2-(1-phenyl-3,4 - dihydroisoquinolin-2(1H)-yl)-1,6-dihydropyrimidine-4-carboxa mide (1.2 g, 1.24 mmol) in acetic acid (20.0 mL) was heated at 180 °C for 2 h in microwave. After completion, the reaction mixture was concentrated to obtain crude product which was purified by CombiFlash. The desired fractions were concentrated to afford 5-methoxy-3-methyl-6-(oxazolo[5,4-c]pyridin-2-yl)-2-(1-pheny l-3,4- dihydroisoquinolin-2(1H)-yl)pyrimidin-4(3H)-one (720 mg, 62%). [00373] Step 5: To a stirred solution of 5-methoxy-3-methyl-6-(oxazolo[5,4-c]pyridin-2-yl)-2-(1- phenyl-3,4-dihydroisoquinolin-2(1H)-yl)pyrimidin-4(3H)-one (0.7 g, 1.51 mmol) in DMF (7.0 mL) was added lithium bromide (654 mg, 5 eq., 7.53 mmol) and the solution was stirred at 100 °C for 16 h. After completion of the reaction, the reaction mixture was concentrated and then ice cold water was added in it to obtain a solid which was filtered. The solid obtained washed with acetonitrile and then with methanol to obtain the product (Racemic) which was separated into two enantiomers by chiral HPLC. The desired fractions were concentrated to afford 6-(benzo[d]oxazol-2-yl)-5-hydroxy-3-methyl-2-(1-phenyl-3,4- dihydroisoquinolin-2(1H)-yl)pyrimidin-4(3H)-one (52 mg, 7%) and 6-(benzo[d]oxazol-2-yl)-5-hydroxy- 3-methyl-2-(1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl)pyrimid in-4(3H)-one (42 mg, 6%) as two different enantiomers. [00374] Enantiomer 1: ES MS M/Z=451.20 [M+H] ⁺ ; ¹ H NMR (400 MHz, DMSO-d6) δ 10.53 (s, 1H), 7.91-7.87 (m, 2H), 7.52-7.45 (m, 2H), 7.27-7.09 (m, 8H), 6.84 (d, J = 8.0 Hz, 1H), 6.00 (s, 1H), 3.57- 3.53 (m, 4H), 3.26-3.21 (m, 2H), 2.99-2.92 (m, 1H). [00375] Enantiomer 2: ES MS M/Z=451.20 [M+H] ⁺ , NMR (400 MHz, DMSO-d ₆ ) δ 10.53 (s, 1H), 7.92-7.87 (m, 2H), 7.53-7.45 (m, 2H), 7.27-7.09 (m, 8H), 6.85 (d, J = 7.60 Hz, 1H), 6.00 (s, 1H), 3.57- 3.53 (m, 4H), 3.26-3.24 (m, 2H), 2.99-2.95 (m, 1H). Example 30: Synthesis of 6-(1,3-benzoxazol-2-yl)-5-hydroxy-3-methyl-2-(1-phenyl-2,3-d ihydro-1H- isoindol-2-yl)-3,4-dihydropyrimidin-4-one

[00376] Step 1: To a stirred solution of 2,3-dihydro-1H-isoindole-1,3-dione (5 g, 34 mmol) in THF (0.1 L, 1.23 mol), was added phenyllithium (4.28 g, 1.5 eq., 51 mmol) at -78 °C. The resultant reaction mixture was allowed to stir at -78 °C for 16 h. After completion of the reaction quenched with saturated of ammonium chloride solution (30 mL) and extracted with EtOAc (50 mL). The organic layer was separated, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. Crude compound was purified by using CombiFlash chromatography to afford 3-hydroxy-3-phenyl-2,3- dihydro-1H-isoindol-1-one (5 g, 65%) as. LC-MS(ES)m/z: 208.1 [M-17]-. [00377] Step 2: To a stirred solution of 3-hydroxy-3-phenyl-2,3-dihydro-1H-isoindol-1-one (5 g, 22.2 mmol) in trifluoroacetic acid (10 mL) was added triethylsilane (7.68 g, 3 eq., 66.6 mmol). The resultant reaction mixture was allowed to stir at ambient temperature for 5 min. After completion of the reaction it was concentrated under reduced pressure. The crude obtained was dissolved in water (30 mL) and extracted with EtOAC (50 mL). The organic layer was separated, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude was purified by CombiFlash chromatography to afford 3-phenyl-2,3-dihydro-1H-isoindol-1-one (1 g, 21.53%). LC-MS(ES)m/z: 210.1 [M+H] ⁺ . [00378] Step 3: To a stirred solution of 3-phenyl-2,3-dihydro-1H-isoindol-1-one (350 mg, 1.67 mmol) in THF (5 mL) was added boron dimethyl sulfate (0.952 mL, 6 eq., 10 mmol) at 0 °C and the mixture was stirred at 75 °C for 16 h. Upon completion, the reaction mixture was cooled to 0 °C and was diluted with 1N HCl and extracted with EtOAc. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford crude product which was purified by CombiFlash chromatography to afford 1-phenyl-2,3-dihydro-1H-isoindole (195 mg, 60%) as viscous liquid. LC- MS(ES)m/z: 196.1 [M+H] ⁺ . [00379] Step 4: To a stirred solution of 1-phenyl-2,3-dihydro-1H-isoindole (195 mg, 0.999 mmol) and methyl 2-chloro-5-methoxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-ca rboxylate (279 mg, 1.2 eq., 1.2 mmol) in DMF(6 mL) was added DIPEA (0.330 mL, 2 eq., 2 mmol) and the mixture was stirred at 110 °C for 16 h. After completion, the reaction mixture was diluted with water and the compound was extracted using EtOAc. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford crude product which was purified by CombiFlash chromatography (using gradient elution 40-50% EtOAc-Hexane) to afford methyl 5-methoxy-1-methyl-6-oxo-2-(1-phenyl-2,3- dihydro-1H-isoindol-2-yl)-1,6-dihydropyrimidine-4-carboxylat e (218 mg, 56%). LC-MS(ES)m/z: 392.2 [M+H] ⁺ . [00380] Step 5: To a stirred solution of methyl 5-methoxy-1-methyl-6-oxo-2-(1-phenyl-2,3-dihydro- 1H-isoindol-2-yl)-1,6-dihydropyrimidine-4-carboxylate (218 mg, 0.557 mmol) in THF (5 mL), methanol (3 mL) and water (1 mL) was added lithium hydroxide (40 mg, 3 eq., 1.67 mmol) and the mixture was stirred at ambient temperature for 2 h. After completion, the solvent was evaporated completely. The crude was diluted with water and pH adjusted to ~2 with 1N HCl. The aqueous layer was extracted with EtOAc (50 mL x 3) and washed with water. The organic layer was dried over sodium sulfate and evaporated in vacuo to afford 5-methoxy-1-methyl-6-oxo-2-(1-phenyl-2,3-dihydro-1H-isoindol -2-yl)- 1,6-dihydropyrimidine-4-carboxylic acid (0.2 g, 95%). LCMS(ES)m/z: 378.0 [M+H] ⁺ . [00381] Step 6: To a stirred solution of 5-methoxy-1-methyl-6-oxo-2-(1-phenyl-2,3-dihydro-1H- isoindol-2-yl)-1,6-dihydropyrimidine-4-carboxylic acid (205 mg, 0.543 mmol) in DMF (5 mL), diisopropyl ethylamine (301 µL, 3 eq., 1.63 mmol), HATU (310 mg, 1.5 eq., 0.815 mmol) and 2- iodoaniline (131 mg, 1.1 eq., 0.598 mmol) were added and the mixture was stirred at ambient temperature for 2 h. After completion, the reaction mixture was diluted with ice water, extracted with EtOAc, and combined organic layers were washed with brine and dried over anhydrous sodium sulfate to provide the crude which was purified by CombiFlash chromatography 30-60% EtOAc in Heptane to provide the N-(2-iodophenyl)-5-methoxy-1-methyl-6-oxo-2-(1-phenyl-2,3-di hydro-1H-isoindol-2-yl)- 1,6-dihydropyrimidine-4-carboxamide (180 mg, 57%). LCMS(ES)m/z: 579.1 [M+H] ⁺ . [00382] Step 7: To a stirred solution of N-(2-iodophenyl)-5-methoxy-1-methyl-6-oxo-2-(1-phenyl-2,3- dihydro-1H-isoindol-2-yl)-1,6-dihydropyrimidine-4-carboxamid e (0.1 g, 0.173 mmol) in acetonitrile (5 mL), cesium carbonate (84.5 mg, 1.5 eq., 0.259 mmol) was added and the mixture was purged with nitrogen for 5 min. Then copper iodide (1.65 mg, 0.05 eq., 0.0864 mmol) and 1,10-phenanthroline (3.12 mg, 0.1 eq., 0.017 mmol) was added and the mixture was purged again with nitrogen for 5 min. The reaction mixture was closed and stirred at 110 °C for 16 h. After completion of the reaction, the reaction mixture was diluted with water and extracted with EtOAc. The combined organic layer washed with brine and dried over anhydrous sodium sulfate to provide the crude which was purified by CombiFlash chromatography to provide the 6-(1,3-benzoxazol-2-yl)-5-methoxy-3-methyl-2-(1-phenyl-2,3-d ihydro- 1H-isoindol-2-yl)-3,4-dihydropyrimidin-4-one (40 mg, 52%). LCMS(ES)m/z: 451.1 [M+H] ⁺ . [00383] Step 8: To a stirred solution of 6-(1,3-benzoxazol-2-yl)-5-methoxy-3-methyl-2-(1-phenyl-2,3- dihydro-1H-isoindol-2-yl)-3,4-dihydropyrimidin-4-one (40 mg, 88.8 µmol) in DMF(15 mL) was added lithium bromide (38.6 mg, 5 eq., 0.444 mmol) at ambient temperature. The mixture was heated at 100 °C for 16 h. After completion of the reaction the mixture was diluted with saturated ammonium chloride and extracted with EtOAc, the combined organic layers were washed with brine, dried over anhydrous sodium sulfate, and concentrated to provide the crude. The crude compound was purified by preparative HPLC to afford 6-(1,3-benzoxazol-2-yl)-5-hydroxy-3-methyl-2-(1-phenyl-2,3-d ihydro-1H-isoindol-2- yl)-3,4-dihydropyrimidin-4-one (5.6 mg, 14%). LC-MS(ESI): 437.2 [M+H] ⁺ ; ¹ H NMR (400 MHz, DMSO d6) δ ppm: 10.30 (s, 1H), 7.93-7.88 (m, 2H), 7.54-7.43 (m, 5H), 7.36-7.20 (m, 5H), 7.08 (d, J=8.0Hz, 1H), 6.80 (s, 1H), 5.43 (d, J=12.0Hz, 1H), 4.71 (d, J=12.0Hz, 1H), 3.60 (s, 3H). Example 40 and 41: 6-(1,3-benzoxazol-2-yl)-5-hydroxy-3-methyl-2-(1-phenyl-2,3-d ihydro-1H- isoindol-2-yl)-3,4-dihydropyrimidin-4-one [00384] Intermediate 8 was separated by chiral HPLC and the two isomers were carried forward through Step 8 of example 24 to provide: [00385] Isomer 1: LCMS(ESI)m/z: 437.3 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO d6) δ ppm: 10.29 (s, 1 H), 7.92 - 7.87 (m, 2 H), 7.53 - 7.42 (m, 5 H), 7.35 - 7.27 (m, 4 H), 7.25 - 7.19 ( m , 1 H ), 7.08 (d, J = 8.0 Hz, 1H), 6.79 (s, 1 H), 5.44 (d, J = 13 Hz, 1 H), 4.73 (d, J = 14 Hz, 1 H), 3.59 (s, 3 H). Stereochemistry arbitrarily assigned. [00386] Isomer 2: LCMS(ESI)m/z: 437.3 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO d6) δ ppm: 10.29 (s, 1H), 7.92 - 7.87 (m, 2H), 7.53 - 7.42 (m, 5H), 7.35 - 7.19 (m, 5 H), 7.08 (d, J = 8.0 Hz, 1H), 6.79 (s, 1H), 5.43 (d, J = 12.8 Hz, 1H), 4.71 (d, J = 14 Hz, 1H), 3.59 (s, 3H). Stereochemistry arbitrarily assigned. Example 31: 5-hydroxy-3-methyl-6-{[1,3]oxazolo[4,5-c]pyridin-2-yl}-2-(1- phenyl-1,2,3,4- tetrahydroisoquinolin-2-yl)-3,4-dihydropyrimidin-4-one [00387] Step 1: To a stirred solution of methyl 2-chloro-5-methoxy-1-methyl-6-oxo-1,6- dihydropyrimidine-4-carboxylate (1.11 g, 4.78 mmol) in DMSO (10.0 mL) was added 1-phenyl-1,2,3,4- tetrahydroisoquinoline (1 g, 4.78 mmol) and DIPEA (918 µL, 1.1 eq., 5.26 mmol) and the solution was stirred at 110 °C for 16 h. After completion, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain crude product which was purified by flash chromatography. The desired fractions were concentrated to provide methyl 5-methoxy-1-methyl-6-oxo-2-(1-phenyl-1,2,3,4-tetrahydroisoqu inolin-2- yl)-1,6-dihydropyrimidine-4-carboxylate (1.2 g, 2.9 mmol, 60%). [00388] Step 2: To a stirred solution of methyl 5-methoxy-1-methyl-6-oxo-2-(1-phenyl-1,2,3,4- tetrahydroisoquinolin-2-yl)-1,6-dihydropyrimidine-4-carboxyl ate (0.6 g, 1.48 mmol) in THF (4.5 mL) and water (1.5 mL, 83.3 mmol) was added lithium hydroxide (177 mg, 5 eq., 7.4 mmol) and the mixture was stirred at ambient temperature for 16 h. After completion, the reaction mixture was acidified with HCl and then concentrated under reduced pressure to afford 5-methoxy-1-methyl-6-oxo-2-(1-phenyl- 1,2,3,4-tetrahydroisoquinolin-2-yl)-1,6-dihydropyrimidine-4- carboxylic acid (550 mg, 1.31 mmol, 88%) (crude). [00389] Step 3: To a stirred solution of 5-methoxy-1-methyl-6-oxo-2-(1-phenyl-1,2,3,4- tetrahydroisoquinolin-2-yl)-1,6-dihydropyrimidine-4-carboxyl ic acid (1 g, 2.55 mmol) in toluene (20 mL) was added DIPEA (892 µL, 2 eq., 5.11 mmol) and the solution was cooled to 0 °C and 1- propanephosphonic anhydride (2.44 g, 3 eq., 7.66 mmol) was added and it was irradiated at 190 °C for 1 h in microwave. After completion of the reaction, the mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain crude product which was purified by flash chromatography. The desired fractions were concentrated to provide 5-methoxy-3-methyl-6-{[1,3] oxazolo [4,5-c] pyridin-2-yl}-2-(1-phenyl-1,2,3,4- tetrahydroisoquinolin-2-yl)-3,4-dihydropyrimidin-4-one (570 mg, 43%). [00390] Step 4: To a solution of 5-methoxy-3-methyl-6- {[1,3] oxazolo[4,5-c] pyridin-2-yl}-2-(1- phenyl-1,2,3,4-tetrahydroisoquinolin-2-yl)-3,4-dihydropyrimi din-4-one (570 mg, 1.22 mmol) in DMF (15.0 mL) was added lithium bromide (532 mg, 5 eq., 6.12 mmol) and the mixture was stirred for 3 days at 100 °C. After completion, the reaction was cooled to ambient temperature, concentrated, diluted with water, and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated o get crude product which was purified by reverse phase HPLC and desired fractions were lyophilized to afford 5-hydroxy-3-methyl-6- {[1,3] oxazolo[4,5-c] pyridin-2-yl}-2-(1- phenyl-1,2,3,4-tetrahydroisoquinolin-2-yl)-3,4-dihydropyrimi din-4-one (17 mg, 3%). ES MS M/Z = 452.25 [M+H] ⁺ ; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.54 (brs, 1H), 10.19 (brs, 1H), 9.17 (s, 1H), 8.63 (d, J = 5.6 Hz, 1H), 7.99 (d, J = 5.6 Hz,1H), 7.27 (m, 8H), 6.85 (d, J = 7.6 Hz, 2H), 5.99 (s,1H), 3.56 (s, 4H), 3.25 (s, 3H), 3.23-3.20 (m, 1H), 2.99-2.94 (m, 1H). [00391] The following compound was synthesized in a similar manner: Example 32: 5-hydroxy-3-methyl-6-(oxazolo[4,5-b]pyridin-2-yl)-2-(1-pheny l-3,4- dihydroisoquinolin-2(1H)-yl)pyrimidin-4(3H)-one [00392] ES MS M/Z = 452.3 [M+H] ⁺ , UPLC: 95%; ¹ H NMR (400 MHz, DMSO-d6) δ 8.51 (m, 1 H), 8.20 (s, 1 H), 7.42 (m, 1 H), 7.28-7.25 (m, 4 H), 7.18 - 7.09 (m, 5 H), 6.82 - 6.80 (m, 1 H), 5.98 (s, 1 H), 3.42 (s, 3 H), 3.16 (m, 2 H), 2.94 (m, 2 H). Example 33: Synthesis of 6-(1,3-benzoxazol-2-yl)-2-[(diphenylmethyl)(ethyl)amino]-5-h ydroxy-3- methyl-3,4-dihydropyrimidin-4-one

[00393] Step 1: To a stirred solution of methyl 2-chloro-5-methoxy-1-methyl-6-oxo-1,6- dihydropyrimidine-4-carboxylate (3 g, 12.9 mmol) in DMSO (10 mL), was added 1,1- diphenylmethanamine (2.68 mL, 15.5 mmol) and DIPEA (3.38 mL, 19.3 mmol). The resultant reaction mixture was allowed to stir at 120 °C for 2 h. Reaction mixture was partitioned between ethyl acetate (100 mL) and water (100 mL). The organic layer was separated, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain crude compound. Crude compound was purified by CombiFlash to afford methyl 2-[(diphenylmethyl)amino]-5-methoxy-1-methyl-6-oxo-1,6- dihydropyrimidine-4-carboxylate (4 g, 76%). ES MS M/Z =380.2 [M+H] ⁺ . [00394] Step 2: To a stirred solution of methyl 2-[(diphenylmethyl)amino]-5-methoxy-1-methyl-6-oxo- 1,6-dihydropyrimidine-4-carboxylate (1.8 g, 4.74 mmol) in THF (9 mL), was added methanol (3.6 mL) followed by the addition of lithium hydroxide (0.341 g, 3 eq., 14.2 mmol) in water (3.6 mL). The resultant reaction mixture was allowed to stir at ambient temperature for 30 min. Completion of the reaction was monitored by TLC. The reaction mixture was concentrated under reduced pressure then partitioned between ethyl acetate (30 mL) and water (30 mL). The aqueous layer was acidified using acetic acid (5 mL) and extracted with ethyl acetate (50 mL). The organic layer was separated, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to afford 2- [(diphenylmethyl)amino]-5-methoxy-1-methyl-6-oxo-1,6-dihydro pyrimidine-4-carboxylic acid (1.3 g, 93%). ES MS M/Z =366.1 [M+H] ⁺ . [00395] Step 3: To a stirred solution of 2-[(diphenylmethyl)amino]-5-methoxy-1-methyl-6-oxo-1,6- dihydropyrimidine-4-carboxylic acid (1.3 g, 3.56 mmol) in DMF (12.7 mL), was added DIPEA (1.86 mL, 10.7 mmol) followed by the addition of 2-iodoaniline (1.17 g, 5.34 mmol) and HATU (1.26 g, 5.34 mmol). The resultant reaction mixture was allowed to stir at ambient temperature for 16 h. Completion of the reaction was monitored by TLC. The reaction mixture was partitioned between ethyl acetate (50 mL) and water (50 mL). The organic layer washed with sodium bicarbonate solution and brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain crude compound. Crude compound was purified by CombiFlash to afford 2-[(diphenylmethyl)amino]-N-(2-iodophenyl)-5- methoxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide (1.9 g, 94%) as a pale yellow solid. ES MS M/Z =567.1 [M+H] ⁺ . [00396] Step 4: To a stirred solution of 2-[(diphenylmethyl)amino]-N-(2-iodophenyl)-5-methoxy-1- methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide (0.5 g, 0.0883 mmol) in acetonitrile (2.98 mL), was added cesium carbonate (431 mg, 1.32 mmol) and the reaction mixture was degassed for 10 minutes, then 1,10-phenanthroline (15.9 mg, 0.883 mmol) and copper iodide (16.8 mg, 0.00883 mmol) were added. The resultant reaction mixture was allowed to stir at 110 °C for 16 h. Completion of the reaction was monitored by TLC. Reaction mixture was partitioned between ethyl acetate (50 mL) and water (50 mL). The organic layer was separated, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. Crude compound was purified by combi-flash to afford 6-(1,3-benzoxazol-2-yl)-2- [(diphenylmethyl)amino]-5-methoxy-3-methyl-3,4-dihydropyrimi din-4-one (0.250 g, 52%). ES MS M/Z =439.1 [M+H] ⁺ . [00397] Step 5: To a stirred solution of 6-(1,3-benzoxazol-2-yl)-2-[(diphenylmethyl)(ethyl)amino]-5- methoxy-3-methyl-3,4-dihydropyrimidin-4-one (40 mg, 0.0857 mmol) in DMF (5 mL) was added lithium bromide (44.7 mg, 6 eq., 0.514 mmol) at ambient temperature. The mixture was heated at 100 °C for 16 h. The reaction was monitored by TLC and LCMS. After completion of the reaction, the mixture was diluted with saturated ammonium chloride and extracted with the DCM. The combined organic layer washed with brine and dried over anhydrous sodium sulfate, then concentrated to provide the crude. The crude compound was purified by preparative HPLC to afford 6-(1,3-benzoxazol-2-yl)-2- [(diphenylmethyl)(ethyl)amino]-5-hydroxy-3-methyl-3,4-dihydr opyrimidin-4-one (12 mg, 31%). ES MS M/Z =453.3 [M+H]; ¹ H NMR (400 MHz, DMSO-d6) δ ppm: 10.6 (s, 1H), 7.88 (t, J=8 Hz, 2 H), 7.47- 7.51 (m, 6H), 7.28 (t, J= 7.6 Hz, 4H), 7.16 (t, J=7.6 Hz, 2H), 5.76(s, 1H), 3.67 (s, 3 H), 3.06-3.08 (m, 2H), 0.98 (t, J=12 Hz,3H). Example 34: 5-hydroxy-3-methyl-6-(oxazolo[5,4-b]pyridin-2-yl)-2-(1-pheny l-3,4 dihydroisoquinolin- 2(1H)-yl)pyrimidin-4(3H)-one [00398] Step 1: To a solution of 5-methoxy-1-methyl-6-oxo-2-(1-phenyl-1,2,3,4-tetrahydroisoqu inolin- 2-yl)-1,6-dihydropyrimidine-4-carboxylic acid (1 g, 2.55 mmol) and 2-chloropyridin-3-amine (361 mg, 1.1 eq., 2.81 mmol) in DMF, was added DIPEA (825 mg, 2.5 eq., 1.28 mmol) and HATU (1.45 g, 1.5 eq., 766 mmol) and the mixture was stirred at ambient temperature for 16 h. After completion, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by flash chromatography. The desired fractions were concentrated to afford methyl N-(2-chloropyridin-3-yl)-5- methoxy-1-methyl-6-oxo-2-(1-phenyl-1,2,3,4-tetrahydroisoquin olin-2-yl)-1,6-dihydropyrimidine-4- carboxamide (0.4 g, 797 mmol). (0.4 g, 31%). [00399] Step 2: To a stirred solution of N-(2-chloropyridin-3-yl)-5-methoxy-1-methyl-6-oxo-2-(1- phenyl-1,2,3,4-tetrahydroisoquinolin-2-yl)-1,6-dihydropyrimi dine-4-carboxamide (0.3 g, 598 µmol) in toluene (15 mL) was added potassium carbonate (165 mg, 2 eq., 1.2 mmol), methyl[2- (methylamino)ethyl]amine (10.5 mg, 0.2 eq., 120 µmol). The reaction mixture was purged with nitrogen for 10 minutes and copper iodide (22.8 mg, 0.2 eq., 120 µmol) was added under nitrogen. The resulting mixture was stirred in the microwave at 110 °C for 4 h. The reaction was monitored by TLC. The mixture was concentrated under reduced pressure and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by flash chromatography. The desired fractions were concentrated to afford 5- methoxy-3-methyl-6-{[1,3]oxazolo[5,4-b]pyridin-2-yl}-2-(1-ph enyl-1,2,3,4-tetrahydroisoquinolin-2-yl)- 3,4-dihydropyrimidin-4-one (95 mg, 204 µmol). (95 mg, 34%). [00400] Step 3: To a stirred solution of 3-({[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2-yl](methyl)amino}(phenyl)methyl)benzonitr ile (80 mg, 168 µmol) in DMF (2 mL) was added bromolithium (87 mg, 6 eq., 1.01 mmol) under nitrogen. The reaction mixture was stirred at 100 °C for 16 h. The progress of the reaction was monitored by LC-MS. After completion, the reaction mixture was concentrated under reduced pressure and extracted with ethyl acetate (2 x 15 mL). The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain crude. The crude was prep HPLC purified to obtain 3-({[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2-yl](methyl)amino}(phenyl)methyl)benzonitr ile (20 mg, 26%). ES-MS M/Z = 452.25 [M+H] ⁺ , UPLC: 99.53%; ¹ H NMR (400 MHz, DMSO-d6) δ 10.73 (bs, 1H), 8.44–8.43 (m, 1H), 8.33– 8.31 (m, 1H), 7.54 (dd, J = 5.2 Hz, 1H), 7.26–7.24 (m, 3H), 7.21–7.16 (m, 3H), 7.13–7.08 (m, 2H), 6.85 (d, J = 7.6 Hz, 1H), 6.0 (s, 1H), 3.56–3.55 (m, 4H), 3.25–3.20 (m, 2H), 2.99–2.94 (m, 1H). Example 35 and 36: 6-(benzo[d]oxazol-2-yl)-2-(((3-cyclopropylphenyl) (phenyl)methyl) (methyl)amino)-5-hydroxy-3-methylpyrimidin-4(3H)-one

[00401] Step 1: To a stirred solution of 6-(1,3-benzoxazol-2-yl)-2-{[(3-bromophenyl) (phenyl)methyl](methyl)amino}-5-methoxy-3-methyl-3,4-dihydro pyrimidin-4-one (250 mg, 0.00470 mmol) in toluene (5 mL) and water (1 mL) was added potassium dihydrogen phosphate (128 mg, 2 eq., 0.0941 mmol), cyclopropylboronic acid (48.5 mg, 1.2 eq., 0.0565 mmol), tricyclohexylphosphane (13.2 mg, 0.1 eq., 0.047 mmol) and the mixture was purged with nitrogen for 15 minutes. Palladium diacetate (10.6 mg, 0.1 eq., 0.0047 mmol) was then added and the mixture was stirred at 100 °C for 1 h in a CEM microwave. After completion of the reaction, the mixture was diluted with water and extracted into ethyl acetate. Combined organic layers were washed with brine solution, dried over anhydrous sodium sulfate and concentrated to obtain the crude product which was purified by combi-flash chromatography to obtain 6-(1,3-benzoxazol-2-yl)-2- {[(3-cyclopropyl phenyl) (phenyl) methyl] (methyl) amino}-5- methoxy-3-methyl-3,4-dihydro pyrimidin-4-one (150 mg, 64.74%). ES MS M/Z =493.1 [M+H] ⁺ [00402] Step 2: To a stirred solution of 6-(1,3-benzoxazol-2-yl)-2-{[(3-cyclopropylphenyl) (phenyl)methyl](methyl)amino}-5-methoxy-3-methyl-3,4-dihydro pyrimidin-4-one (150 mg, 0.030 mmol) in DMF (5 mL) was added lithium bromide (212 mg, 8 eq., 2.44 mmol) and the mixture was stirred at 100 °C for 16 h. After completion of the reaction, the reaction mixture was diluted with saturated ammonium chloride and extracted with the dichloromethane. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, and concentrated to obtain the crude product to afford 6-(1,3-benzoxazol-2-yl)-2-{[(3-cyclopropylphenyl) (phenyl)methyl](methyl)amino}-5- hydroxy-3-methyl-3,4-dihydropyrimidin-4-one Isomer-1 (6 mg, 4%) and 6-(1,3-benzoxazol-2-yl)-2- {[(3-cyclopropylphenyl) (phenyl)methyl](methyl)amino}-5-hydroxy-3-methyl-3,4-dihydro pyrimidin-4- one Isomer-2 (8 mg, 5%). [00403] Isomer-1: ES MS M/Z =479.4 [M+H] ⁺ , ¹ H NMR (400 MHz, DMSO d6) δ ppm: 10.55 (s, 1H), 7.86 (d, J = 7.6 Hz, 2H), 7.43-7.51 (m, 4H), 7.28 (t, J = 8Hz, 2H), 7.20-7.10 (m ,4H), 6.84 (d, J = 8Hz, 2H), 5.66 (s, 1H), 3.66 (s, 3H), 2.56 (s, 3H), 1.84-1.80 (m, 1H), 0.86-0.81 (m, 2H), 0.56-0.53 (m, 2H). [00404] Isomer-2: ES MS M/Z =479.4 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO d6) δ ppm: 10.51 (s, 1H), 7.81 (d, J = 7.6 Hz, 2H), 7.49-7.40 (m, 7H), 7.07-7.25 (m, 9H), 6.80 (d, J = 8Hz, 2H), 5.66 (d, J = 24Hz, 1H), 3.64 (s, 3H), 2.55 (s, 3H), 1.79 (m, 1H), 0.81-0.79 (m, 2H), 0.52 (m, 2H). [00405] The following compound was synthesized in a similar manner: Example 42: 6-(benzo[d]oxazol-2-yl)-5-hydroxy-3-methyl-2-(methyl(phenyl( m-tolyl) methyl) amino) pyrimidin-4(3H)-one [00406] ES MS M/Z=453.25 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d6) δ 10.55 (br s, 1H), 7.86 (t, J = 6.00 Hz, 2H), 7.51-7.44 (m, 4H), 7.30-7.25 (m, 4H), 7.16 (t, J = 7.60 Hz, 2H), 6.97 (d, J = 7.60 Hz, 1H), 5.68 (s, 1H), 3.66 (s, 3H), 2.57 (s, 3H), 2.23 (s, 3H). Example 37: 4-({[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6-di hydropyrimidin-2- yl](methyl)amino} (phenyl)methyl)-N, N-dimethylbenzamide [00407] Step 1: To a stirred solution of 4-({[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2-yl] (methyl)amino} (phenyl) methyl) benzoic acid (0.180 g, 0363 mmol) and dimethyl amine HCl (0.059 g, 0.725 mmol) in DMF (2 mL) was added ethylbis(propan-2-yl) amine (0.095 mL, 0.544 mmol), [bis(dimethylamino)methylidene] ({3H-[1,2,3] triazolo[4,5-b]pyridin-3- yl})oxidanium (0.128 g, 0.544 mmol) and the mixture was stirred for 16 h at ambient temperature. After completion, the reaction mixture was diluted with wáter, extractad with ethyl acetate, dried over sodium sulfate, and concentrated. The crude compound was purified by combi-flash chromatography to obtain 4- ({[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxo-1,6-dihy dropyrimidin-2-yl] (methyl) amino} (phenyl)methyl)-N, N-dimethylbenzamide (0.150 g, 77%) as a yellow semi-solid. ES MS M/Z = 524.3 [M+H] ⁺ . [00408] Step 2: To a stirred solution of 4-({[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2-yl] (methyl)amino} (phenyl)methyl)-N, N-dimethylbenzamide (0.150 g, 0.286 mmol) in DMF (5 mL) was added lithium bromide (0.249 g, 2.86 mmol) at ambient temperature and the mixture was stirred at 110 °C for 16 h. After completion it was diluted with saturated ammonium chloride, extracted with the dichloromethane, and the combined organic layers were washed with brine, dried over anhydrous sodium sulfate, concentrated. The crude compound was purified by preparative HPLC to afford 4-({[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6-di hydropyrimidin-2- yl](methyl)amino}(phenyl)methyl)-N,N-dimethylbenzamide (0.017 g, 12%). ES MS M/Z = 510.4 [M+H] ⁺ ; UPLC: 99.15%; ¹ H NMR (400 MHz, DMSO-d6) δ ppm: 10.56 (s, 1 H), 7.85 (m, 2 H), 7.5 (m, 6 H), 7.30 (m, 4 H), 7.18 (m, 1 H), 5.76 (s, 1 H), 3.67 (s, 3 H), 2.89 (s, 3 H), 2.75 (s, 3 H), 2.59 (s, 3 H). Example 43: 3-(((4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6-di hydropyrimidin-2- yl)(methyl)amino)(phenyl)methyl)-N,N-dimethylbenzamide [00409] ES MS M/Z=510.30 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d6) δ 10.54 (br s, 1H), 7.84 (t, J = 6.40 Hz, 2H), 7.55-7.44 (m, 6H), 7.34-7.29 (m, 4H), 7.21 (t, J = 7.20 Hz, 1H), 7.13 (d, J = 7.60 Hz, 1H), 5.76 (s, 1H), 3.68 (s, 3H), 2.85 (s, 3H), 2.59 (s, 6H). Example 44: 3-(((4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6-di hydropyrimidin-2- yl)(methyl)amino)(phenyl)methyl)-N-methylbenzamide [00410] ES MS M/Z=496.35 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d6) δ 10.52 (s, 1H), 8.38 (q, J = 4.00 Hz, 1H), 7.97 (s, 1H), 7.84 (d, J = 8.40 Hz, 2H), 7.61 (dd, J = 1.60, 8.00 Hz, 2H), 7.51-7.43 (m, 4H), 7.37-7.28 (m, 3H), 7.18 (t, J = 7.20 Hz, 1H), 5.78 (s, 1H), 3.68 (s, 3H), 2.73 (d, J = 4.40 Hz, 3H), 2.57 (s, 3H). Example 38: 2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6-dihy dropyrimidin-2-yl]-1- cyclobutyl-1H-1,3-benzodiazole-6-carboxamide [00411] Step 1: To a stirred solution of 4-(1,3-benzoxazol-2-yl)-5-ethoxy-1-methyl-6-oxo-1,6- dihydropyrimidine-2-carbaldehyde (1 g, 3.34 mmol) and 4-amino-3-(cyclobutylamino)benzonitrile (501 mg, 0.8 eq., 2.67 mmol) in DMF (20 mL) and water (4 mL) was added oxone monopersulfate (1.03 g, 3.34 mmol) and stirred at ambient temperature for 16 h. The reaction was monitored by TLC & LCMS. After completion of the reaction, it was quenched with water and extracted with 10% methanol in DCM. The organic layer was dried over sodium sulfate, filtered, and concentrated. The crude was purified by Combi-flash chromatography and desired fractions were concentrated to obtain 2-[4-(1,3-benzoxazol-2- yl)-5-ethoxy-1-methyl-6-oxo-1,6-dihydropyrimidin-2-yl]-1-cyc lobutyl-1H-1,3-benzodiazole-6- carbonitrile (0.9 g, 1.77 mmol) as brownish solid (0.90 g, 53%). [00412] Step 2: To a stirred solution of 2-[4-(1,3-benzoxazol-2-yl)-5-ethoxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2-yl]-1-cyclobutyl-1H-1,3-benzodiazole-6-ca rbonitrile (0.5 g, 1.07 mmol) in DMSO (4 mL), was added peroxol (108 µL, 1.5 eq., 1.61 mmol) followed by dipotassium carbonate (741 mg, 5 eq., 5.36 mmol) at 0 °C, after 5 minutes stirred at ambient temperature for 16 h. The reaction was then poured in water and the solid precipitate was filtered to afford 2-[4-(1,3-benzoxazol-2-yl)-5-ethoxy-1-methyl-6- oxo-1,6-dihydropyrimidin-2-yl]-1-cyclobutyl-1H-1,3-benzodiaz ole-6-carboxamide (0.1 g, 175 µmol) as a colorless solid (0.10 g, 16%). [00413] Step 3: To a stirred solution of 2-[4-(1,3-benzoxazol-2-yl)-5-ethoxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2-yl]-1-cyclobutyl-1H-1,3-benzodiazole-6-ca rboxamide (0.1 g, 206 µmol) in DMF (2 mL), was added lithium bromide (89.6 mg, 5 eq., 1.03 mmol) and stirred at 100 °C for 16 h. After completion of the reaction, the mixture was concentrated under reduced pressure, the residue was diluted with ice cold water, and the resulting mixture was filtered under vacuum. The residue was washed with DCM and dried under vacuum to afford 2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2-yl]-1-cyclobutyl-1H-1,3-benzodiazole-6-ca rboxamide (20 mg, 41.2 µmol) (0.02 g, 20%). ES MS M/Z = 457.25 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.29 (bs s, 1H), 8.14 (bs s, 1H), 7.86 (d, J = 8 Hz, 1H), 7.76 (d, J = 8 Hz, 1H), 7.62 (d, J = 8 Hz, 1H), 7.53 (d, J = 7.8 Hz, 1H), 7.40 (bs s, 1H), 7.32-7.25 (m, 2H), 5.17 (t, J = 8 Hz, 8 Hz, 1H), 3.36 (s, 3H), 2.62-2.50 (m, 4H), 1.96-1.76 (m, 2H). Example 39: 3-(2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6-d ihydropyrimidin-2-yl)- 1,2,3,4-tetrahydroisoquinolin-1-yl) benzoic acid [00414] Step 1: To a stirred solution of methyl 2-phenylacetate (10 g, 66.6 mmol) in THF (100 mL) was added sodium borohydride (6.3 g, 2.5 eq., 166 mmol) at 0 °C. Then iodine (10.1 g, 1.2 eq., 79.9 mmol) in THF (100 mL) was added slowly drop-wise at 0 °C and stirred at 80 °C for 12 h. After completion of the reaction, it was quenched with ice cold water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, and concentrated. The crude was purified by combiflash to afford 2-phenylethan-1-ol (6 g, 73.76%). ¹ H NMR [400 MHz, CDCl3]: δ ppm 7.36 - 7.32 (m, 2H), 7.28 – 7.24 (m, 3H), 3.89 (t, J = 6.4 Hz, 2H), 2.90 (t, J = 6.4 Hz, 2H). [00415] Step 2: To a stirred solution of 2-phenylethan-1-ol (2 g, 16.4 mmol) in 1,2-dichloroethane (60 mL) was added 3-bromobenzonitrile (3.28 g, 1.1 eq., 18 mmol), 2-fluoropyridine (1.59 g, 16.4 mmol) & trifluoromethanesulfonyl (5.53 mL, 2 eq., 32.7 mmol) at 0 °C. The mixture was stirred at ambient temperature for 30 mins and then heated to 80 °C for 16 h. After completion of the reaction the mixture was concentrated then extracted with ethyl acetate. The organic layer was washed with saturated NaHCO ₃ solution, brine, dried over anhydrous sodium sulfate, and concentrated. The crude was purified by combiflash to afford 1-(3-bromophenyl)-3,4-dihydroisoquinoline (1.9 g, 41%) as a yellow liquid. ES MS M/Z = 288.0 [M+H] ⁺ . [00416] Step 3: To a stirred solution of 1-(3-bromophenyl)-3,4-dihydroisoquinoline (1.9 g, 6.64 mmol) in methanol (30 mL, 741 mmol) was added sodium borohydride (754 mg, 3 eq., 19.9 mmol) at 0 °C. The mixture was stirred at ambient temperature for 1 h. After completion of the reaction, the reaction mixture was diluted with saturated ammonium chloride and extracted with ethyl acetate. The organic layer was washed with brine solution, dried over anhydrous sodium sulfate, and concentrated. The crude was purified by combiflash to obtain 1-(3-bromophenyl)-1,2,3,4-tetrahydroisoquinoline (1.8 g, 94%) as a light yellow solid. ES MS M/Z = 290.0 [M+2H] ⁺ . [00417] Step 4: To a stirred solution of 1-(3-bromophenyl)-1,2,3,4-tetrahydroisoquinoline (1.8 g, 6.25 mmol) in DMSO (50 mL) was added DIPEA (1.2 mL, 1.1 eq., 6.87 mmol) and methyl 2-chloro-5- methoxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxylate (1.45 g, 6.25 mmol) at ambient temperature. The mixture was heated at 110°C for 16 h. After completion of the reaction, it was diluted with water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude was purified by combiflash using 5-50% ethyl acetate/heptane to afford methyl 2-[1-(3-bromophenyl)-1,2,3,4-tetrahydroisoquinolin-2-yl]-5-m ethoxy-1-methyl-6-oxo-1,6- dihydropyrimidine-4-carboxylate (0.9 g, 30%). ES MS M/Z = 484.1 [M+H] ⁺ . [00418] Step 5: To a stirred solution of methyl 2-[1-(3-bromophenyl)-1,2,3,4-tetrahydroisoquinolin-2- yl]-5-methoxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxy late (0.9 g, 1.86 mmol) in THF (5 mL), methanol (5 mL,) and water (1 mL) was added lithium hydroxide (156 mg, 2 eq., 3.72 mmol) at ambient temperature. The reaction mixture was stirred at RT for 2 h. after completion solvent was removed under reduced pressure. The crude was dissolved in water and washed with diethyl ether (10 mL). The aqueous layer was acidified with 1N HCl up to PH ~2, extracted with 10% MeOH/DCM, dried over sodium sulfate, and concentrated to afford 2-[1-(3-bromophenyl)-1,2,3,4-tetrahydroisoquinolin-2-yl]-5-m ethoxy- 1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxylic acid (850 mg, crude). ES MS M/Z = 470.1 [M+H] ⁺ . [00419] Step 6: To a stirred solution of 2-[1-(3-bromophenyl)-1,2,3,4-tetrahydroisoquinolin-2-yl]-5- methoxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxylic acid (0.1 g, 0.213 mmol) and 2- aminophenol (25.5 mg, 1.1 eq., 0.234 mmol) in THF (10 mL) was added 1-(1H-imidazole-1-carbonyl)- 1H-imidazole (51.7 mg, 1.5 eq., 0.319 mmol) at 0 °C under N ₂ atmosphere. The mixture was heated at 60 °C for 16 h. After completion of the reaction, it was diluted with wáter, extracted with ethyl acetate, dried over anhydrous sodium sulfate, and concentrated. The crude was purified by combiflash to afford 2-[1- (3-bromophenyl)-1,2,3,4-tetrahydroisoquinolin-2-yl]-N-(2-hyd roxyphenyl)-5-methoxy-1-methyl-6-oxo- 1,6-dihydropyrimidine-4-carboxamide (0.07 g, 58%). ES MS M/Z = 563.1 [M+H] ⁺ . [00420] Step 7: To a stirred solution of 2-[1-(3-bromophenyl)-1,2,3,4-tetrahydroisoquinolin-2-yl]-N- (2-hydroxyphenyl)-5-methoxy-1-methyl-6-oxo-1,6-dihydropyrimi dine-4-carboxamide (70 mg, 0.125 mmol) in acetic acid (2 mL) was irradiated in CEM microwave at 180 °C for 2 h. After completion of the reaction, it was concentrated. The crude was purified by combi-flash chromatography to afford 6-(1,3- benzoxazol-2-yl)-2-[1-(3-bromophenyl)-1,2,3,4-tetrahydroisoq uinolin-2-yl]-5-methoxy-3-methyl-3,4- dihydropyrimidin-4-one (50 mg, 71.58%). ES MS M/Z = 543.1 [M+H] ⁺ . [00421] Step 8: To a stirred solution of 6-(1,3-benzoxazol-2-yl)-2-[1-(3-bromophenyl)-1,2,3,4- tetrahydroisoquinolin-2-yl]-5-methoxy-3-methyl-3,4-dihydropy rimidin-4-one (0.5 g, 0.920 mmol) in a mixture of 1,2-dimethoxyethane (10 mL) and water (8 mL) was added sodium carbonate (146 mg, 1.5 eq., 1.38 mmol). Tetrafluoroborohydride; tri-tert-butylphosphanium (26.7 mg, 0.1 eq., 0.092 mmol), hexakis(methanidylidyneoxidanium) molybdenum (364 mg, 1.5 eq., 1.38 mmol) was then added and the mixture was purged with nitrogen gas for 10 minutes. Then palladium diacetate (20.7 mg, 0.1 eq., 0.092 mmol) was added and the mixture was stirred for 1 h at 120°C in microwave. After completion, the mixture was evaporated and the residue was diluted with water and washed with ethyl acetate. The aqueous layer was acidified with 1N HC1 solution (pH~2), extracted with DCM, dried over magnesium sulfate, and concentrated under reduced pressure to obtain 3-{2-[4-(1,3-benzoxazol-2-yl)-5-methoxy-1- methyl-6-oxo-1,6-dihydropyrimidin-2-yl]-1,2,3,4-tetrahydrois oquinolin-1-yl} benzoic acid (150 mg, crude). ES MS M/Z = 509.2 [M+H] ⁺ . [00422] Step 9: To a stirred solution of 3-{2-[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2-yl]-1,2,3,4-tetrahydroisoquinolin-1-yl} benzoic acid (150 mg, 0.103 mmol) in DMF (5 mL) was added lithium bromide (26.9 mg, 3 eq., 0.310 mmol) at ambient temperature and the mixture was heated at 95 °C for 16 hours. After completion, the reaction mixture poured into wáter, extracted with ethyl acetate, dried over magnesium sulfate, and concentrated. The crude compound was purified by prep HPLC to afford 3-{2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6-d ihydropyrimidin-2- yl]-1,2,3,4-tetrahydroisoquinolin-1-yl} benzoic acid (5 mg, 10%). ES MS M/Z = 495.2 [M+H] ⁺ . NMR (400 MHz, DMSO-d6) δ ppm 12.81 (s, 1H), 10.51 (s, 1H), 7.92- 7.85 (m, 3 =H),7.69 (d, J = 7.6 Hz, 1H),7.52-7.44 (m, 3H), 7.33-7.27 (m, 2H), 7.19 (t, J = 7.2 Hz, 1H),7.11 (t, J = 7.2 Hz, 1H), 6.81 (d, J = 7.6 Hz, 1H), 6.06 (s, 1H), 3.61-3.57 (m, 1H), 3.55 (s, 3H), 3.26-3.2 (m, 2H), 2.99-2.95 (m, 1H). Example 45 and 46: -3-({[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6-d ihydropyrimidin- 2-yl](methyl)amino}(phenyl)methyl)benzoic acid

[00423] Step 1: To a stirred solution of 3-bromobenzaldehyde (10 g, 54 mmol) in dichloromethane (70 mL) were added cesium carbonate (26.4 g, 1.5 eq., 81.1 mmol), 2-methylpropane-2-sulfinamide (7.86 g, 1.2 eq., 64.9 mmol) and stirred at 40 °C for 16 hours. After completion of the starting material, reaction mixture was diluted with water (15 mL) and the compound was extracted with dichloromethane. The combined organic layer dried over anhydrous sodium sulfate and evaporated under reduced pressure to afford N-[(E)-(3-bromophenyl) methylidene]-2-methylpropane-2-sulfinamide (14.5 g, 90.3% yield) as yellow liquid. ES MS M/Z =290 [M+2H] ⁺ . [00424] Step 2: To a stirred solution of N-[(Z)-(3-bromophenyl) methylidene]-2-methylpropane-2- sulfinamide (15 g, 19.1 mmol) in tetrahydrofuran (50 mL), was added phenyllithium (1.92 g, 1.2 eq., 22.9 mmol) at -78 °C. The resultant reaction mixture was allowed to stir at room temperature for 16 hours. After completion of the reaction, the reaction mixture was quenched with saturated ammonium chloride solution (50 mL) and extracted with ethyl acetate (100 mL). Organic layer was separated, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to get crude. The crude was purified by flash column chromatography using 40-50% ethyl acetate in n-heptane as an eluent to afford N-[(3-bromophenyl) (phenyl)methyl]-2-methylpropane-2-sulfinamide (13.1 g, 58.4% ) as yellow gummy liquid. ES MS M/Z =366.1 [M+H] ⁺ . [00425] Step 3: To a stirred solution of N-[(3-bromophenyl) (phenyl)methyl]-2-methylpropane-2- sulfinamide (13.1 g, 35.9 mmol) in dichloromethane (55 mL) was added 4M hydrogen chloride in 1,4- dioxane (2.62 g, 2 eq., 71.7 mmol) at 0 °C. The resultant reaction mixture was allowed to stir at room temperature for 2 hours. After completion of reaction, reaction mixture was evaporated under reduced pressure. Residue obtained was washed with n-pentane and diethyl ether to afford 1-(3-bromophenyl)-1- phenylmethanamine hydrochloride (10.5 g, 35.2 mmol) as colorless solid. ¹ H NMR (400 MHz, DMSO- d6) δ ppm: 9.14 (s, 2H), 7.97 (s, 1H), 7.40-7.76 (m, 3H), 7.01-7.38 (m, 5H), 5.65 (s, 1H). [00426] Step 4: To a stirred solution of 1-(3-bromophenyl)-1-phenylmethanamine hydrochloride (10.4 g, 34.8 mmol) in dimethyl sulfoxide (100 mL) slowly added ethylbis(propan-2-yl) amine (18.2 mL, 3 eq., 104 mmol) after 10 min added methyl 2-chloro-5-methoxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4- carboxylate (8.1 g, 34.8 mmol) at room temperature. The resulting reaction mixture was allowed to stir at 120 °C for 2 hours. After completion of the reaction, the reaction mixture was quenched with water (100 mL) and extracted with ethyl acetate (2 x 100 mL). The combined organic layer was washed with brine, dried with anhydrous sodium sulfate, and evaporated under reduced pressure to afford crude. The crude was purified with flash column chromatography using 40-50% ethyl acetate in n-heptane as eluents to afford methyl 2-{[(3-bromophenyl) (phenyl)methyl] amino}-5-methoxy-1-methyl-6-oxo-1,6- dihydropyrimidine-4-carboxylate (6.5 g, 40%) as colorless solid. ES MS M/Z =459.9 [M+H] ⁺ . [00427] Step 5: To a stirred solution of methyl 2-{[(3-bromophenyl) (phenyl)methyl] amino}-5- methoxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxylate (6.5 g, 14.2 mmol) in dimethylformamide (38 mL) were added cesium carbonate (13.9 g, 3 eq., 42.5 mmol) followed by iodo methane (1.3 mL, 22.3 mmol) and stirred at room temperature for 2 hours. After completion of the reaction, the reaction mixture was diluted with water (100 mL) and extracted with ethyl acetate (2 x 100 mL). The organic layer dried over anhydrous sodium sulfate, filtered, and evaporated under reduced pressure to afford methyl 2-{[(3-bromophenyl) (phenyl)methyl] (methyl)amino}-5-methoxy-1-methyl-6-oxo-1,6- dihydropyrimidine-4-carboxylate (6 g, 87%) as yellow liquid. ES MS M/Z =474.1 [M+2H] ⁺ . [00428] Step 6: To a stirred solution of methyl 2-{[(3-bromophenyl) (phenyl)methyl] (methyl)amino}- 5-methoxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxylate (6.5 g, 13.8 mmol) in mixture of tetrahydrofuran (35 mL), methanol (35 mL) and water (10 mL) was added lithium hydroxide (1.62 g, 5 eq., 67.6 mmol). The resulting reaction mixture was allowed to stir at room temperature for 2 hours. After completion of the reaction concentrated under reduced pressure. Then the crude was acidified to pH=2 using 1N HCl solution and extracted with ethyl acetate (3 x 50 mL). Organic layer was washed with water, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to afford 2-{[(3- bromophenyl) (phenyl)methyl] (methyl)amino}-5-methoxy-1-methyl-6-oxo-1,6-dihydropyrimidin e-4- carboxylic acid (6 g, 88%) as yellow gummy solid. ES MS M/Z =460.1 [M+2H] ⁺ . [00429] Step 7: To a stirred solution of 2-{[(3-bromophenyl) (phenyl)methyl] (methyl)amino}-5- methoxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxylic acid (6 g, 13.1 mmol) and 2-iodoaniline (1.42 g, 1.1 eq., 6.48 mmol) in dimethylformamide (80 mL) were added ethylbis(propan-2-yl)amine (7.25 mL, 3 eq., 39.3 mmol), hexafluoro-λ⁵-phosphanuide 1-[bis(dimethylamino)methylidene]-1H-1λ⁵- [1,2,3]triazolo[4,5-b]pyridin-3-ium-1-ylium-3-olate (7.47 g, 1.5 eq., 19.6 mmol) and stirred at room temperature for 4 h. After completion of the reaction, reaction mixture was diluted with ice water and extracted with ethyl acetate. The combined organic layer was washed with brine solution, dried over anhydrous sodium sulfate, and evaporated to get the crude. The crude compound was purified by combi flash chromatography 40-50% ethyl acetate in heptane to afford 2-{[(3-bromophenyl) (phenyl)methyl] (methyl)amino}-N-(2-iodophenyl)-5-methoxy-1-methyl-6-oxo-1,6 -dihydropyrimidine-4-carboxamide (4.77 g, 42%) as a pale yellow solid. ES MS M/Z =659.0 [M+H] ⁺ . [00430] Step 8: To a stirred solution of 2-{[(3-bromophenyl) (phenyl)methyl] (methyl)amino}-N-(2- iodophenyl)-5-methoxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4 -carboxamide (4.77 g, 7.23 mmol) in acetonitrile (127 mL) were added cesium carbonate (3.54 g, 1.5 eq., 10.9 mmol), copper iodide (68.9 mg, 0.05 eq., 0.362 mmol) and 1,10-phenanthroline (130 mg, 0.1 eq., 0.723 mmol). Then the reaction was purged with nitrogen for 15 minutes and stirred at 110 °C for 16 hours. After completion of the reaction, reaction mixture was diluted with water and extracted into ethyl acetate. Combined organic layer was washed with brine solution, dried over anhydrous sodium sulfate, and concentrated to get the crude. The crude compound was purified by combi flash chromatography 30-40% ethyl acetate in heptane to get the crude compound. The crude was purified by chiral HPLC using analytical conditions: Column: CHIRALPAK IC (100 mm X 4.6mm X 3 µm), Mobile phase: MTBE: IPA in 0.1 DEA (70:30) Flow rate: 1.0 mL/min, to afford Isomer-16-(1,3-benzoxazol-2-yl)-2-{[(3-bromophenyl) (phenyl)methyl] (methyl)amino}-5-methoxy-3-methyl-3,4-dihydropyrimidin-4-one (0.4 g, 10%), RT = 2.971 ES MS M/Z = 531.1 [M+H] ⁺ and Isomer-26-(1,3-benzoxazol-2-yl)-2-{[(3-bromophenyl) (phenyl)methyl] (methyl)amino}-5-methoxy-3-methyl-3,4-dihydropyrimidin-4-one (0.4 g, 10%) as off-colorless solid. RT= 4.787, ES MS M/Z = 531.1 [M+H] ⁺ . [00431] Step 9a: (Isomer-1): To a stirred solution of 6-(1,3-benzoxazol-2-yl)-2-{[(3-bromophenyl) (phenyl)methyl] (methyl)amino}-5-methoxy-3-methyl-3,4-dihydropyrimidin-4-one (0.4 g, 0.753 mmol) in mixture of 1,2-dimethoxyethane (10 mL) and water (6.67 mL) was added sodium carbonate (120 mg, 1.5 eq., 1.13 mmol). Followed by the additions of tetrafluoroboranuide; tri-tert-butylphosphanium (21.8 mg, 0.1 eq., 0.0753 mmol) and hexakis(methanidylidyneoxidanium) molybdenum (298 mg, 1.5 eq., 1.13 mmol) purged with nitrogen gas for 10 minutes. Then was added palladium diacetate (16.9 mg, 0.1 eq., 0.0753 mmol) and stirred for 1h at 120 °C in microwave. Solvent was evaporated, the residue was diluted with water and washed with ethyl acetate. The aqueous layer was acidified by IN HC1 solution (pH ~2), extracted with dichloromethane, dried over magnesium sulfate, and concentrated under reduced pressure to get crude. The crude compound was purified by combi flash chromatography 30-40% EtOAc in Heptane to get the 3-({[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxo-1,6-di hydropyrimidin-2-yl] (methyl)amino} (phenyl)methyl) benzoic acid (0.2 g, 53.51%) as a yellow solid. ES MS M/Z = 497.0 [M+H] ⁺ . [00432] Step 9b: (Isomer-2): To a stirred solution of 6-(1,3-benzoxazol-2-yl)-2-{[(3-bromophenyl) (phenyl)methyl] (methyl)amino}-5-methoxy-3-methyl-3,4-dihydropyrimidin-4-one (370 mg, 0.696 mmol) in mixture of 1,2-dimethoxyethane (10 mL) and water (8 mL) was added sodium carbonate (111 mg, 1.5 eq., 1.04 mmol). Followed by the additions of tetrafluoroboranuide; tri-tert-butylphosphanium (20.2 mg, 0.1 eq., 0.0696 mmol) and hexakis(methanidylidyneoxidanium) molybdenum (276 mg, 1.5 eq., 1.04 mmol) purged with nitrogen gas for 10 minutes. Then was added palladium diacetate (15.6 mg, 0.1 eq., 0.0696 mmol) and stirred for 1 hour at 120°C in microwave. Solvent was evaporated, the residue was diluted with water and washed with ethyl acetate. The aqueous layer was acidified by IN HC1 solution (pH~2), extracted with dichloromethane, dried over magnesium sulfate, and concentrated under reduced pressure to get the crude. The crude compound was purified by combi flash chromatography 30-40% EtOAc in Heptane to get the 3-({[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2-yl] (methyl)amino} (phenyl)methyl) benzoic acid (170 mg, 49%) as a yellow solid. ES MS M/Z = 497.0 [M+H] ⁺ . [00433] Step 10a (Isomer-1): To a stirred solution of 3-({[4-(1,3-benzoxazol-2-yl)-5-methoxy-1- methyl-6-oxo-1,6-dihydropyrimidin-2-yl] (methyl)amino} (phenyl)methyl) benzoic acid (0.2 g, 0.403 mmol) in dimethylformamide (8 mL) was added lithium bromide (350 mg, 10 eq., 4.03 mmol) at room temperature and stirred at 110 °C for 16 hours. After completion of the reaction, reaction mixture was diluted with saturated ammonium chloride and extracted with 10% methanol in DCM. The combined organic layer washed with brine solution, dried over anhydrous sodium sulfate, and concentrated to get the crude. The crude compound was purified by reverse phase HPLC using Conditions: Column: Inertsil ODS C18 (250x20) mm;5mic, Flow: -19ml/min Mobile phase (A):0.1%Formic acid in water, Mobile phase(B): Acetonitrile, to afford 3-({[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2-yl] (methyl)amino} (phenyl)methyl) benzoic acid (60 mg, 30.87%). ES MS M/Z = 483.4 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ ppm: 12.93 (s, 1 H), 10.54 (s, 1 H), 8.03 (s, 1 H), 7.85 (m, 2 H), 7.72 (m, 2 H), 7.50 (m, 5 H), 7.30 (m, 2 H), 7.21 (m, 1 H), 5.82 (s, 1 H), 3.67 (s, 3 H), 2.59 (s, 3 H), Melting Point: 205-210 ° C. [00434] Step 10b: (Isomer-2): To a stirred solution of 3-({[4-(1,3-benzoxazol-2-yl)-5-methoxy-1- methyl-6-oxo-1,6-dihydropyrimidin-2-yl] (methyl)amino} (phenyl)methyl) benzoic acid (170 mg, 0.342 mmol) in dimethylformamide (5 mL) was added lithium bromide (297 mg, 10 eq., 3.42 mmol) at room temperature and stirred at 110 °C for 16 hours. After completion of the reaction, reaction mixture was diluted with saturated ammonium chloride and extracted with the dichloromethane. The combined organic layer washed with brine solution, dried over anhydrous sodium sulfate, and concentrated to get the crude. The crude compound was purified by reverse phase using conditions Column: X-Bridge C- 18(250 mm X 4.6 mm X 5 mic), Mobile phase (A): 0.1% Formic Acid in water, Mobile phase (B): Acetonitrile, Flow rate: 1.0 ml/min, to afford 3-({[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxo- 1,6-dihydropyrimidin-2 yl] (methyl)amino} (phenyl)methyl) benzoic acid (23 mg, 14%). ES MS M/Z = 483.3 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ ppm: 12.94 (s, 1 H), 10.53 (s, 1 H), 8.03 (s, 1 H), 7.85 (m, 2 H), 7.73 (m, 2 H), 7.49 (m, 5 H), 7.30 (m, 2 H), 7.21 (m, 1 H), 5.82 (s, 1 H), 3.67 (s, 3 H), 2.59 (s, 3 H). Melting point: 200 - 203 °C. [00435] Intermediate 12 was separated by chiral HPLC and the two isomers were carried forward through Steps 9 and 10 to provide: [00436] Isomer 1: ES MS M/Z = 483.4 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ ppm: 12.93 (s, 1 H), 10.54 (s, 1 H), 8.03 (s, 1 H), 7.85 (m, 2 H), 7.72 (m, 2 H), 7.50 (m, 5 H), 7.30 (m, 2 H), 7.21 (m, 1 H), 5.82 (s, 1 H), 3.67 (s, 3 H), 2.59 (s, 3 H). [00437] Isomer 2: ES MS M/Z = 483.3 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d6) δ ppm: 12.94 (s, 1 H), 10.53 (s, 1 H), 8.03 (s, 1 H), 7.85 (m, 2 H), 7.73 (m, 2 H), 7.49 (m, 5 H), 7.30 (m, 2 H), 7.21 (m, 1 H), 5.82 (s, 1 H), 3.67 (s, 3 H), 2.59 (s, 3 H). Example 47 and 48: 4-(((4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6-di hydropyrimidin- 2-yl) (methyl)amino) (phenyl)methyl) benzoic acid Intermediate 9 was separated by chiral HPLC and the two isomers were carried forward through Steps 9 and 10 to provide: [00438] ^{Isomer 1: ES MS M/Z = 483.3 [M+H]+. 1H NMR (400 MHz, DMSO-d} 6 ^{) δ ppm: 12.7 (bs, 1H),} 10.49 (bs, 1H), 7.86 (m, 4H), 7.61 (m, 2H), 7.48 (m, 4H), 7.30 (m, 2H), 7.19 (m, 1H), 5.81 (s, 1H), 3.69 (s, 3H), 2.59 (s, 3H). Stereochemistry arbitrarily assigned. [00439] Isomer 2: ES MS M/Z = 483.3 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d6) δ ppm: 12.79 (s, 1H), 10.54 (s, 1H), 7.86 (m, 4H), 7.61 - 7.59 (d, J = 8.4 Hz, 2H), 7.49 (m, 4H), 7.30 (m, 2H), 7.19 (m, 1H), 5.81 (s, 1H), 3.68 (s, 3H), 2.58 (s, 3H). Stereochemistry arbitrarily assigned. Example 50: (1R)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyri midin-2-yl]-N,N-dimethyl- 1-(2-methylphenyl)-3,4-dihydro-1H-isoquinoline-7-carboxamide [00440] A solution of (1R)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyri midin-2-yl]-1-(2- methylphenyl)-3,4-dihydro-1H-isoquinoline-7-carboxylic acid (20 mg, 1 equiv), PyBOP (62 mg, 3 equiv), DIEA (21 mg, 4 equiv) and dimethylamine hydrochloride (5 mg, 1.5 equiv) in DMF (1.5 mL) was stirred for 3 h at 20 °C under N ₂ atmosphere. The crude product was purified by prep-HPLC with the following conditions (Column: XSelect CSH C ₁₈ Column, 19*250 mm, 5 μm; Mobile Phase A: Water (0.1% FA), Mobile Phase B: acetonitrile; Flow rate: 25 mL/min; Gradient: 42% B to 72% B in 7 min; Wave Length: 254 nm; RT(min): 6.33) to afford (1R)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6- oxopyrimidin-2-yl]-N,N-dimethyl-1-(2-methylphenyl)-3,4-dihyd ro-1H-isoquinoline-7-carboxamide (3 mg, 14%) as a yellow solid. ES MS M/Z = 536.3 [M+H] ⁺ , UPLC:99%. (300 MHz, DMSO-d6) δ 7.90-7.81 (m, 2 H), 7.58-7.43 (m, 2 H), 7.35-7.13 (m, 3 H), 7.13-6.90 (m, 3 H), 6.66 (s, 1 H), 6.20 (s, 1 H), 3.69 - 3.55 (m, 4 H), 3.46-3.30 (m, 1 H),3.29-3.15 (m, 1H), 2.97 (s, 1 H), 2.89 (s, 3 H), 2.75(s, 3 H), 2.56 (s, 3 H). Stereochemistry arbitrarily assigned. [00441] The following compounds were synthesized in a similar manner with the appropriate amine and carboxylic acid starting materials: Example 51: 2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6-dihy dropyrimidin-2-yl)-1- (2-methoxyphenyl)-N,N-dimethyl-1,2,3,4-tetrahydroisoquinolin e-7-carboxamide [00442] ES MS M/Z = 552 [M+H] ⁺ , UPLC: 95%; ¹ H NMR (300 MHz, DMSO-d6) 8.39 - 8.21 (m, 6 H), 8.15 - 7.95 (m,1 H), 7.89 - 7.72 (m, 1 H), 7.51 - 7.32 (m, 2 H), 7.31 - 7.02 (m, 4 H), 7.02 - 6.93 (m, 1 H), 6.92 - 6.81 (m, 2 H), 6.80 - 6.71 (m, 1 H), 6.45 - 6.31(m, 1 H), 4.79 - 4.71 (m, 3 H), 3.75 - 3.63 (m, 3 H), 3.39 - 3.23 (m, 2 H), 3.05 - 2.89 (m, 5 H) , 2.83 - 2.78(m, 3 H). Example 52: (S)-2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2-yl)- N,N-dimethyl-1-(o-tolyl)-1,2,3,4-tetrahydroisoquinoline-7-ca rboxamide [00443] ES MS M/Z = 536.2 [M+H] ⁺ , UPLC:99%. ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 7.88 - 7.84 (m, 2H), 7.54 - 7.45 (m, 2H), 7.33 - 7.30 (m, 1H), 7.25 - 7.16 (m, 2H), 7.10 - 6.99 (s, 1H), 6.66 (s, 2H), 6.20 (s, 1H), 3.76 - 3.51 (m, 4H), 3.41 - 3.33 (m, 2H), 3.24 - 3.17 (m, 1H), 2.97 - 2.88 (s, 1H), 2.74 (s, 3H), 2.56 (s, 3H), 2.51 - 2.50 (m, 2H). Stereochemistry arbitrarily assigned. Example 53: (1R)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyri midin-2-yl]-1-(2- methylphenyl)-3,4-dihydro-1H-isoquinoline-7-carboxamide [00444] ES MS M/Z = 508.2 [M+H] ⁺ , UPLC:97%. ¹ H NMR (300 MHz, DMSO-d6) δ 10.95-10.11 (m, 1H), 7.91-7.78 (m, 3H), 7.67 (d, J = 6.9, 1H), 7.56-7.39 (m, 2H), 7.31 (d, J = 8.1, 1H), 7.25 (s, 2H), 7.19- 7.10 (m, 1H), 7.09-7.05 (m, 1H), 7.02 - 6.95 (m, 2H), 6.23 (s, 1H), 3.68 - 3.59 (m, 1H), 3.55 (s, 3H), 3.51-3.39 (m, 1H), 3.25-3.11 (m, 1H), 2.99-2.88(m, 1H), 2.56 (s, 3H). Stereochemistry arbitrarily assigned. Example 54: (S)-2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2-yl)- 1-(o-tolyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide [00445] ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 8.36 - 8.35 (s, 2H), 8.28 - 8.26 (s, 1H), 7.86 (s, 1H), 7.66 - 7.63 (m, 1H), 7.50 - 7.46 (s, 1H), 7.42 - 7.20 (m, 4H), 7.02 - 6.97 (m, 2H), 6.17(s, 1H), 3.45 - 3.36 (s, 4H), 3.42 - 3.66 (m, 2H), 2.51 - 2.49 (m, 3H). Stereochemistry arbitrarily assigned. Example 55: (R)-2-(4-(5,6-dihydro-4H-cyclopenta[d]oxazol-2-yl)-5-hydroxy -1-methyl-6-oxo-1,6- dihydropyrimidin-2-yl)-1-phenyl-1,2,3,4-tetrahydroisoquinoli ne-7-carboxamide [00446] ES MS M/Z = 484.2 [ -d6) δ 8.29 (s, 2H), 7.74 (d, J = 7.9 Hz, 1H), 7.46 (d, J = 1.8 Hz, 1H), 7.37 (d, J = 8.1 Hz, 1H), 7.24 – 7.12 (m, 5H), 5.99 (s, 1H), 3.52 (s, 4H), 3.26 – 3.21 (m, 2H), 3.08 – 3.02 (m, 1H), 2.83 (s, 3H), 2.58 – 2.51 (m, 4H). Stereochemistry arbitrarily assigned. Example 56: 2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6-dihy dropyrimidin-2-yl)-3- phenylisoindoline-5-carboxamide _[00447] ES MS M/Z = 480.15 [M+H] ⁺ . UPLC: 96%, ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.23 (s, 1H), 8.10 - 7.70 (m, 3H), 7.65 - 7.04 (m, 10H), 6.65 (s, 1H), 5.54 - 5.13 (m, 1H), 4.77 - 4.42 (m, 1H), 3.58 (s, 3H). Example 57: 2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6-dihy dropyrimidin-2-yl)-1- (2-methoxyphenyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxami de [00448] ES MS M/Z = 524.15 [M+H] ⁺ , UPLC: 97%; ¹ H NMR (300 MHz, DMSO-d6) 8.43 - 8.13 (m, 2 H), 8.12 - 7.82 (m, 2 H), 7.80 - 7.61 (m, 2 H), 7.62 - 7.23 (m, 6 H), 7.21 - 7.01 (m, 1 H), 7.01 - 6.68 (m, 3 H), 6.42 - 6.22 (m, 1 H), 4.73 - 4.69 (m, 3 H), 3.43 – 3.35 (m, 3 H), 3.21 - 3.12 (m, 3 H), 3.11 - 3.01 (m, 1 H). Example 58: (R)-2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2-yl)- 1-(2-fluorophenyl)-N,N-dimethyl-1,2,3,4-tetrahydroisoquinoli ne-7-carboxamide [00449] ES MS M/Z = 540.15 [M+H] ⁺ , UPLC: 96%; ¹ H NMR (400 MHz, DMSO-d6) δ 7.93 - 7.78 (m, 2 H), 7.63 - 7.43 (m, 2 H), 7.41 - 7.31 (m, 1 H), 7.30 - 7.15 (m, 3 H), 7.12 – 6.98 (m, 2 H), 6.97 - 6.85 (m, 1 H), 6.41 - 6.25 (m, 1 H), 3.45 – 3.40 (m, 4 H), 3.21 - 3.38 (m, 2 H), 3.10 – 2.75 (m, 7 H). Stereochemistry arbitrarily assigned. Example 59: (S)-2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2-yl)- 1-(2-methoxyphenyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxa mide [00450] ES MS M/Z = 512.20 [M+H] ⁺ , UPLC: 97%; δ 8.85 – 8.45 (m, 1 H), 7.99 - 7.79 (m, 1 H), 7.78 - 7.52 (m, 2 H), 7.51 - 7.28 (m, 4 H), 7.25 - 7.11 (m, 3H), 7.11 - 6.96 (m, 2 H), 6.39 - 6.12 (m, 1 H), 3.61 - 3.58 (m, 4 H), 3.41 - 3.21 (m, 1 H), 3.20 - 3.04 (m, 1 H), 3.03 - 2.96 (m, 1 H). Stereochemistry arbitrarily assigned. Example 60: 2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6-dihy dropyrimidin-2-yl)- N,N-dimethyl-3-phenylisoindoline-5-carboxamide [00451] ES MS M/Z = 508.20 [M+H] ⁺ , UPLC: 97%, ¹ H NMR (300 MHz, DMSO-d6) δ 10.33 (s, 1H), 7.91 (t, J = 6.4 Hz, 2H), 7.58 – 7.44 (m, 5H), 7.34 – 7.32 (m, 3H), 7.25 (d, J = 7.3 Hz, 1H), 7.09 (s, 1H), 6.84 (s, 1H), 5.46 (d, J = 14.4 Hz, 1H), 4.76 (d, J = 14.3 Hz, 1H), 3.61 (s, 3H), 2.90 (d, J = 19.8 Hz, 6H). Example 61: (1S)-2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6 -dihydropyrimidin-2- yl)-1-(2-fluorophenyl)-N,N-dimethyl-1,2,3,4-tetrahydroisoqui noline-7-carboxamide [00452] ES MS M/Z = 540.20 [M+H] ⁺ , UPLC: 99%; ¹ H NMR (300 MHz, DMSO-d6) δ 7.99 - 7.71 (m, 2 H), 7.66 - 7.42 (m, 2 H), 7.41 - 7.32 (m, 1 H), 7.31 – 6.98 (m, 5 H), 6.98 – 6.81 (m, 1H), 6.42 - 6.21 (m, 1 H), 3.73 - 3.52 (m, 4 H), 3.35 - 3.21 (m, 2 H), 3.12 – 2.95 (m, 1 H), 3.11 – 2.75 (m, 6 H). Stereochemistry arbitrarily assigned. Example 62: (S)-2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2-yl)- 1-(2-fluorophenyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxam ide [00453] ES MS M/Z = 512.20 [M+H] ⁺ , UPLC: 99.506%; δ 7.95 - 7.81 (m, 2 H), 7.80 - 7.62 (m, 1 H), 7.55 - 7.40 (m, 3 H), 7.39 - 7.31 (m, 1 H), 7.29 - 7.01 (m, 4H), 6.42 - 6.21 (m, 1 H), 6.64 - 6.52 (m, 4 H), 6.38 - 6.21 (m, 2 H), 3.12 – 2.92 (m, 1 H). Stereochemistry arbitrarily assigned. Example 63: (1S)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyri midin-2-yl]-1-(2- chlorophenyl)-N,N-dimethyl-3,4-dihydro-1H-isoquinoline-7-car boxamide [00454] ES MS M/Z = 556.2 [M+H] ⁺ , UPLC: 98%; ¹ H NMR (400 MHz, DMSO-d6) δ 8.21 (s, 1H), 7.67 (d, J = 8.1 Hz, 1H), 7.43 - 7.29 (m, 4H), 7.9 - 7.24 (m, 1H), 7.16 - 7.13 (m, 2H), 6.82 (s, 1H), 6.42 - 6.35 (m, 1H), 3.46 - 3.14 (m, 6H), 2.96 - 2.69 (m, 8H). Stereochemisty arbitrarily assigned. Example 64: (1S)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyri midin-2-yl]-1-(2-chloro phenyl)-N,N-dimethyl-3,4-dihydro-1H-isoquinoline-6-carboxami de [00455] ES MS M/Z = 556.1 [M+H] ⁺ , UPLC: 99%; ¹ H NMR (400 MHz, DMSO-d6) δ 7.82-7.89 (m, 2H), 7.42-7.55 (m, 2H), 7.35-7.42 (m, 1H), 7.30 (d, J = 10.3 Hz, 2H), 7.15-7.22 (m, 3H), 6.90 (d, J = 8.0 Hz, 1H), 6.45 (s, 1H), 3.58 (s, 3H), 3.28 (d, J = 9.8 Hz, 1H), 3.25 - 3.29 (m, 2H), 2.93 – 2.96 (m, 7H). Stereochemistry arbitrarily assigned. Example 65: (1R)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyri midin-2-yl]-1-(2- chlorophenyl)-N,N-dimethyl-3,4-dihydro-1H-isoquinoline-6-car boxamide [00456] ^{ES MS M/Z =556.1 [M+H]+, UPLC: 99%;1H NMR (400 MHz, DMSO-d} 6 ^{) δ 7.89 - 7.82 (m,} 2H), 7.55 - 7.42 (m, 2H), 7.42 - 7.35 (m, 1H), 7.30 (d, J = 10.3 Hz, 2H), 7.22 - 7.15 (m, 3H), 6.90 (d, J = 8.0 Hz, 1H), 6.45 (s, 1H), 3.63 – 3.61 (m, 4H), 3.29 - 3.25 (m, 2H), 2.96 - 2.93 (m, 7H). Stereochemistry arbitrarily assigned. Example 66: (1S)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyri midin-2-yl]-1-(2- chlorophenyl)-3,4-dihydro-1H-isoquinoline-6-carboxamide [00457] ES MS M/Z =528.1 [M+H] ⁺ , UPLC: 96%; ¹ H NMR (400 MHz, DMSO-d6) δ 10.58 (s, 1H), 7.94 (s, 1H), 7.86 (t, J = 7.5, Hz, 2H), 7.79 (d, J = 1.8 Hz, 1H), 7.63 (d, J = 8.2,Hz, 1H), 7.49 – 7.47(m, 2H), 7.32 – 7.32 (m, 2H), 7.25 (d, J = 5.1 Hz, 1H), 7.14 – 7.23 (m, 2H), 6.93 (d, J = 8.2 Hz, 1H), 6.46 (s, 1H), 3.62 (d, J = 8.0 Hz, 1H), 3.57 (s, 4H), 3.34 - 3.29 (m, 2H), 2.91 - 3.00 (m, 1H). Stereochemistry arbitrarily assigned. Example 67: (1S)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyri midin-2-yl]-N-methyl-1- phenyl-3,4-dihydro-1H-isoquinoline-7-carboxamide [00458] ES MS M/Z = 508.2 [M+H] ⁺ , UPLC: 97%; ¹ H NMR (300 MHz, DMSO-d6) δ 10.57 (s, 1H), 7.90 – 7.86 (m, 2H), 7.53 - 7.46 (m, 2H), 7.34 – 7.13 (m, 7H), 6.88 (d, J = 1.7 Hz, 1H), 6.04 (s, 1H), 3.57 (s, 4H), 3.29 - 3.27 (m, 2H), 3.02 - 2.98 (m, 1H), 2.90 (s, 3H), 2.78 (s, 3H). Stereochemistry arbitrarily assigned. Example 68: 2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6-dihy dropyrimidin-2-yl)-1- phenyl-1,2,3,4-tetrahydroisoquinoline-7-carboxamide [00459] ES MS M/Z = 494.1 [M+H] ⁺ , UPLC: 99%; ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 10.53 (s, 1H), 7.90 - 7.88 (m, 3H), 7.71 (d, J = 8.0 Hz, 1H), 7.53 - 7.45 (m, 3H), 7.35 (d, J = 8.1 Hz, 1H), 7.27 - 7.11 (m, 6H), 6.07 (s, 1H), 3.56 (s, 4H), 3.25 - 3.22 (m, 2H), 3.03 (d, J = 16.1 Hz, 1H). Example 69: (S)-2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2-yl)- N,N-dimethyl-1-phenyl-1,2,3,4-tetrahydroisoquinoline-7-carbo xamide _[00460] ES MS M/Z = 522.2 [M+H] ⁺ , UPLC: 97%; ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 10.57 (s, 1H), 7.90 – 7.86 (m, 2H), 7.53 - 7.46 (m, 2H), 7.34 – 7.13 (m, 7H), 6.88 (d, J = 1.7 Hz, 1H), 6.04 (s, 1H), 3.57 (s, 4H), 3.29 - 3.27 (m, 2H), 3.02 - 2.98 (m, 1H), 2.90 (s, 3H), 2.78 (s, 3H). Stereochemistry arbitrarily assigned. Example 70: (1R)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyri midin-2-yl]-N,N- dimethyl-1-phenyl-3,4-dihydro-1H-isoquinoline-7-carboxamide [00461] ES MS M/Z = 522.2 [M+H] ⁺ ; ¹ H NMR (400 MHz, DMSO-d6) δ 10.58 (s, 1H), 7.90 – 7.87 (m, 2H), 7.56 – 7.43 (m, 2H), 7.34 (d, J = 7.9 Hz, 1H), 7.31 – 7.18 (m, 5H), 7.18 – 7.10 (m, 1H), 6.88 (d, J = 1.7 Hz, 1H), 6.04 (s, 1H), 3.57 (s, 3H), 3.63 – 3.52 (m, 1H), 3.28 – 3.39 (m, 2H), 3.05 – 2.94 (m, 1H), 2.90 (s, 3H), 2.78 (s, 3H). Stereochemistry arbitrarily assigned. Example 71: (1R)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyri midin-2-yl]-N-methyl-1- phenyl-3,4-dihydro-1H-isoquinoline-7-carboxamide [00462] ES MS M/Z = 508.2 [M+H] ⁺ , UPLC: 96%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.57 (s, 1H), 8.35 – 8.33 (m, 1H), 7.89 (t, J = 7.5 Hz, 2H), 7.66 (d, J = 7.9 Hz, 1H), 7.44 - 7.57 (m, 2H), 7.42 (d, J = 1.8 Hz, 1H), 7.36 (d, J = 8.0 Hz, 1H), 7.18 - 7.29 (m, 4H), 7.10 - 7.18 (m, 1H), 6.07 (s, 1H), 3.56 (s, 3H), 3.56 (d, J = 17.4 Hz, 1H), 3.21 - 3.31 (m, 2H), 2.98 - 3.08 (m, 1H), 2.71 (d, J = 4.4 Hz, 3H). Stereochemistry arbitrarily assigned. Example 72: (1R)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyri midin-2-yl]-1-phenyl- 3,4-dihydro-1H-isoquinoline-7-carboxamide [00463] ES MS M/Z = 494.2 [M+H] ⁺ , UPLC: 96%; ¹ H NMR (400 MHz, DMSO-d6) δ 10.57 (s, 1H), 7.89 – 7.86 (m, 3H), 7.70 (d, J = 7.9 Hz, 1H), 7.43 - 7.56 (m, 3H), 7.35 (d, J = 8.1 Hz, 1H), 7.18 - 7.32 (m, 5H), 7.10 - 7.18 (m, 1H), 6.07 (s, 1H), 3.56 (s, 3H), 3.56 (d, J = 12.6 Hz, 1H), 3.21 - 3.34 (m, 2H), 2.98 - 3.08 (m, 1H). Stereochemistry arbitrarily assigned. Example 73: (1S)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyri midin-2-yl]-1-phenyl- 3,4-dihydro-1H-isoquinoline-6-carboxamide [00464] ES MS M/Z = 494.1 [M+H] ⁺ , UPLC: 99%; ¹ H NMR (400 MHz, DMSO-d6) δ 7.96 – 7.86 (m, 3H), 7.79 (d, J = 1.8 Hz, 1H), 7.60 (d, J = 8.1Hz, 1H), 7.57 – 7.44 (m, 2H), 7.34 (s, 1H), 7.31 – 7.24 (m, 2H), 7.24 – 7.17 (m, 2H), 7.17 – 7.09 (m, 1H), 6.92 (d, J = 8.3 Hz, 1H), 6.05 (s, 1H), 3.63 – 3.56 (m, 1H), 3.57 (s, 3H), 3.35 (s, 1H), 3.38 – 3.19 (m, 1H), 3.01 (d, J = 16.5 Hz, 1H). Stereochemistry arbitrarily assigned. Example 74: (1R)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyri midin-2-yl]-1-phenyl- 3,4-dihydro-1H-isoquinoline-6-carboxamide [00465] ES MS M/Z = 494.1 [M+H] ⁺ , UPLC: 99%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 7.96 – 7.86 (m, 3H), 7.79 (d, J = 1.8 Hz, 1H), 7.60 (d, J = 8.1Hz, 1H), 7.57 – 7.44 (m, 2H), 7.34 (s, 1H), 7.31 – 7.24 (m, 2H), 7.24 – 7.17 (m, 2H), 7.17 – 7.09 (m, 1H), 6.92 (d, J = 8.3 Hz, 1H), 6.05 (s, 1H), 3.63 – 3.56 (m, 1H), 3.57 (s, 3H), 3.35 (s, 1H), 3.38 – 3.19 (m, 1H), 3.01 (d, J = 16.5 Hz, 1H). Stereochemistry arbitrarily assigned. Example 75: (1S)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyri midin-2-yl]-N, N- dimethyl-1-phenyl-3,4-dihydro-1H-isoquinoline-6-carboxamide [00466] ES MS M/Z = 522.15 [M+H] ⁺ , UPLC: 96%; ¹ H NMR (400 MHz, DMSO-d6) δ: 10.58 (s, 1H), 7.94 - 7.85 (m, 2H), 7.56 - 7.43 (m, 2H), 7.37 - 7.25 (m, 3H), 7.25 - 7.09 (m, 4H), 6.90 (d, J = 8.1 Hz, 1H), 6.03 (s, 1H), 3.57 (s, 4H), 3.35 - 3.1(m, 2H), 2.95 (d, J = 14.8 Hz, 7H). Stereochemistry arbitrarily assigned. Example 76: tert-butyl ((3-(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)ureido)(4-(((R)-2- hydroxypropyl)(methyl)carbamoyl)furan-2-yl)(oxo)-l6-sulfaney lidene)carbamate _[00467] ES MS M/Z = 522.15 [M+H] ⁺ , UPLC: 96%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ: 10.58 (s, 1H), 7.94 - 7.85 (m, 2H), 7.56 - 7.43 (m, 2H), 7.37 - 7.25 (m, 3H), 7.25 - 7.09 (m, 4H), 6.90 (d, J = 8.1 Hz, 1H), 6.03 (s, 1H), 3.57 (s, 4H), 3.35 - 3.1(m, 2H), 2.95 (d, J = 14.8 Hz, 7H). Stereochemistry arbitrarily assigned. Example 77: (1S)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyri midin-2-yl]-N-methyl-1- phenyl-3,4-dihydro-1H-isoquinoline-6-carboxamide [00468] ES MS M/Z = 508.1 [M+H] ⁺ , UPLC: 98%; ¹ H NMR (300 MHz, DMSO-d6) δ 10.56 (s, 1H), 8.40 (d, J = 4.8 Hz, 1H), 7.93 -7.88 (m, 2H), 7.73 (s, 1H), 7.57 - 7.45 (m, 3H), 7.30 - 7.11 (m, 5H), 6.93 (d, J = 8.4 Hz, 1H), 6.05 (s, 1H), 3.56 (s, 4H),3.40 - 3.2 (m, 2H), 3.02 (d, J = 15.5 Hz, 1H), 2.78 (d, J = 4.2 Hz, 3H). Stereochemistry arbitrarily assigned. Example 78: (1R)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyri midin-2-yl]-N-methyl-1- phenyl-3,4-dihydro-1H-isoquinoline-6-carboxamide [00469] ES MS M/Z = 508.1 [M+H] ⁺ , UPLC: 98%; ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 10.56 (s, 1H), 8.40 (d, J = 4.8 Hz, 1H), 7.88 – 7.93 (m, 2H), 7.73 (s, 1H), 7.45 – 7.57 (m, 3H), 7.11 – 7.30 (m, 5H), 6.93 (d, J = 8.4 Hz, 1H), 6.05 (s, 1H), 3.56 (s, 4H), 3.21 – 3.40 (m, 2H), 3.02 (d, J = 15.5 Hz, 1H), 2.78 (d, J = 4.2 Hz, 3H). Stereochemistry arbitrarily assigned. Example 79: 2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyrimidin -2-yl]-3-cyclobutyl- N,N-dimethyl-1,3-benzodiazole-5-carboxamide [00470] ES MS M/Z = 485.1 [M+H] ⁺ , UPLC: 97%; ¹ H NMR (300 MHz, DMSO-d6) δ 7.96-7.70 (m, 4H), 7.48 - 7.39 (m, 3H), 5.31 – 5.19 (m, 1H), 3.55 (s, 3H), 3.02 (s, 6H), 2.68 - 2.55 (m, 2H), 2.40 - 2.30 (m, 2H), 1.90 - 1.70 (m, 2H). Example 152: (R)-2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2- yl)-1-(2-cyanophenyl)-N,N-dimethyl-1,2,3,4-tetrahydroisoquin oline-7-carboxamide [00471] ES MS M/Z = 547.3 [M+H] ⁺ , UPLC: 98%. ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 7.85 – 7.84 (m, 2H), 7.81 – 7.83 (m, 1H), 7.58 – 7.52 (m, 4H), 7.37 – 7.35 (m, 2H), 7.28 – 7.25 (m, 1H), 6.78 (s, 1H), 6.31 (s, 1H), 3.60 (s, 5H), 2.90 – 2.63 (m, 8H). Stereochemistry arbitrarily assigned. Example 153: (S)-2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2- yl)-1-(2-cyanophenyl)-N,N-dimethyl-1,2,3,4-tetrahydroisoquin oline-7-carboxamide _[00472] ES MS M/Z = 547.3 [M+H] ⁺ , UPLC: 98%. ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 7.85 – 7.84 (m, 2H), 7.81 – 7.83 (m, 1H), 7.58 – 7.52 (m, 4H), 7.37 – 7.35 (m, 2H), 7.28 – 7.25 (m, 1H), 6.78 (s, 1H), 6.31 (s, 1H), 3.60 (s, 5H), 2.90 – 2.63 (m, 8H). Stereochemistry arbitrarily assigned. Example 80 and 81: (R)-2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2-yl)-1-(2-methoxyphenyl)-1,2,3,4-tetrahydr oisoquinoline-7-carboxamide and (S)-2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2-yl)-1-(2- methoxyphenyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide [00473] 2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyrimidin -2-yl]-1-(2-methoxyphenyl)- 3,4-dihydro-1H-isoquinoline-7-carboxamide (80 mg, 0.153 mmol, 1 equiv) was submitted to prep-SFC with the following conditions: Column: CHIRALPAKIG3; Mobile Phase A: Hex(0.5%TFA): EtOH=60: 40; Flow rate: 1mL/min mL/min; Gradient: isocratic ; Injection Volume: 10L mL. After concentration was provided the products. (R)-2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2-yl)-1-(2-methoxyphenyl)-1,2,3,4-tetrahydr oisoquinoline-7-carboxamide (15.1 mg, 12.48%) as a dark green solid. ES MS M/Z = 524.20 [M+H] ⁺ , UPLC: 99%; ¹ H NMR (300 MHz, DMSO- d ₆ ) δ 7.93 - 7.82 (m, 3 H), 7.79 - 7.67 (m, 1 H), 7.61 - 7.46 (m, 3 H), 7.36 - 7.26 (m, 1 H), 7.28 - 7.21 (m, 1H), 7.19 - 7.01 (m, 1 H), 6.96 - 6.89 (m, 1 H), 6.88 - 6.73 (m, 1 H), 6.73 - 6.63 (m, 1 H), 6.33 - 6.23 (m, 1 H), 3.71 - 3.62 (m, 3 H), 3.59 - 3.52 (m, 3 H), 3.43 - 3.35 (m, 2 H), 3.13 - 3.03 (m, 1 H) and (S)-2-(4- (benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydropy rimidin-2-yl)-1-(2-methoxyphenyl)- 1,2,3,4-tetrahydroisoquinoline-7-carboxamide ES MS M/Z = 524.25 [M+H] ⁺ , UPLC: 97%; ¹ H NMR (300 MHz, DMSO-d6) δ 7.92 - 7.81 (m, 3 H), 7.79 - 7.75 (m, 1 H), 7.71 - 7.52 (m, 3 H), 7.34 - 7.24 (m, 1 H), 7.23 - 7.13 (m, 1H), 6.96 - 6.73 (m, 1 H), 6.94 - 6.72 (m, 1 H), 6.68 - 6.35 (m, 1 H), 6.39 - 6.32 (m, 1 H), 3.63 - 3.57 (m, 6 H), 3.43 - 3.36 (m, 2 H), 3.28 - 3.13 (m, 1 H), 3.12 - 2.98 (m, 1 H). – Stereochemistry arbitrarily assigned. [00474] The following compounds were synthesized in a similar manner: Example 82: (S)-2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2-yl)- 1-(2-methoxyphenyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxa mide [00475] ES MS M/Z = 552.25 [M+H] ⁺ , UPLC: 99%; ¹ H NMR (300 MHz, DMSO-d6) δ 7.91 - 7.81 (m, 2 H), 7.58 - 7.42 (m, 2 H), 7.40 - 7.32 (m, 1 H), 7.28 - 7.22 (m, 1 H), 7.21 - 7.09 (m, 1 H), 6.98 - 6.89 (m, 2 H), 6.88 - 6.73 (m, 2 H), 6.42 - 6.38 (m, 1 H), 3.72 - 3.68 (m, 3 H), 3.66 - 3.63 (m, 3 H), 3.42 - 3.32 (m, 2 H), 3.30 - 3.12 (m, 2 H), 3.02 - 2.98 (m, 1 H), 2.96 – 2.78 (m, 6 H). Stereochemistry arbitrarily assigned. Example 83: (R)-2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2-yl)- 1-(2-methoxyphenyl)-N,N-dimethyl-1,2,3,4-tetrahydroisoquinol ine-7-carboxamide [00476] ES MS M/Z = 552.25 [M+H] ⁺ , UPLC: 96%; ¹ H NMR (300 MHz, DMSO-d6) δ 7.93 - 7.79 (m, 2 H), 7.58 - 7.43 (m, 2 H), 7.35 - 7.31 (m, 1 H), 7.30 - 7.21 (m, 1 H), 7.21 - 7.09 (m, 1 H), 7.01 - 6.89 (m, 2 H), 6.88 - 6.73 (m, 2 H), 6.42 - 6.38 (m, 1 H), 3.73 - 3.67 (m, 3 H), 3.66 - 3.63 (m, 3 H), 3.48 - 3.40 (m, 1 H), 3.40 - 3.32 (m, 1 H), 3.28 - 3.12 (m, 1 H), 3.05 - 2.99 (m, 1 H), 2.98 – 2.80 (m, 6 H). Stereochemistry arbitrarily assigned. Example 84: N-[(1R)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxop yrimidin-2-yl]-1- phenyl-3,4-dihydro-1H-isoquinolin-7-yl]-N-methylacetamide [00477] ES MS M/Z = 522.25 [M+H] ⁺ .UPLC:97% ¹ H NMR (400 MHz, DMSO-d ₆ ) δ7.88 – 7.86 (m, 2H), 7.53 – 7.45 (m, 2H), 7.34 - 7.32 (m, 1H), 7.27 – 7.26 (m, 2H), 7.23 – 7.21 (m, 2H), 7.19 – 7.11 (m, 2H), 6.76 (d, J=0.8Hz, 1H), 6.02 (s, 1H), 3.88 – 3.79 (m, 4H), 3.29 – 3.25 (m, 2H), 3.02 – 2.95 (m, 4H), 1.17 (t, J=14.4Hz, 3H). Stereochemistry arbitrarily assigned. Example 85: N-[(1S)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxop yrimidin-2-yl]-1- phenyl-3,4-dihydro-1H-isoquinolin-7-yl]-N-methylacetamide [00478] ES MS M/Z = 522.25 [M+H] ⁺ , UPLC:97%; ¹ H NMR (400 MHz, DMSO-d6) δ 10.55 (s, 1H), 7.87 (d, J = 7.5 Hz, 2H), 7.56 – 7.43 (m, 2H), 7.34 (d, J = 8.0 Hz, 1H), 7.27 (d, J = 7.2 Hz, 2H), 7.20 – 7.15 (m, 4H), 6.77 (d, J = 2.2 Hz, 1H), 6.03 (s, 1H), 3.56 (s, 3H), 3.52 (d, J = 12.5 Hz, 1H), 3.26 (d, J = 10.5 Hz, 2H), 3.04 (s, 3H), 2.99 – 2.95 (m, 1H), 1.58 (s, 3H). Stereochemistry arbitrarily assigned. Example 86: (R)-2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2-yl)- 1-(2-methoxyphenyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxy lic acid [00479] ES MS M/Z = 525.1 10.76 - 10.4 (m, 1 H), 7.92 - 7.81 (m, 2 H), 7.83 - 7.73 (m, 1 H), 7.68 - 7.54 (m, 1 H), 7.51 - 7.47 (m, 2 H), 7.45 - 7.37 (m, 1 H), 7.23 - 7.13 (m, 1 H), 6.98 - 6.91 (m, 1 H), 6.79 - 6.75 (m, 2 H), 6.63 - 6.37 (m, 1 H), 3.72 - 3.69 (m, 3 H), 3.68 - 3.63 (m, 3 H), 3.36 - 3.32 (m, 2 H), 3.27 - 3.22 (m, 1 H), 3.13 - 2.98 (m, 1 H). Stereochemistry arbitrarily assigned. Example 87: (S)-2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2-yl)- 1-(2-methoxyphenyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxy lic acid [00480] ES MS M/Z = 525.10 [M+H] ⁺ , UPLC: 95%; ¹ H NMR (300 MHz, DMSO-d6) δ 10.7 - 10.3 (m, 1 H), 7.95 - 7.85 (m, 2 H), 7.82 - 7.73 (m, 1 H), 7.70 - 7.53 (m, 1 H), 7.50 - 7.45 (m, 2 H), 7.43 - 7.38 (m, 1 H), 7.19 - 7.15 (m, 1 H), 6.99 - 6.96 (m, 1 H), 6.99 - 6.96 (m, 1 H), 6.78 - 6.76 (m, 2 H), 6.56 - 6.36 (m, 1 H), 3.71 - 3.68 (m, 3 H), 3.67-3.63 (m, 3 H), 3.36 - 3.31 (m, 2 H), 3.26 - 3.21 (m, 1 H), 3.16 - 3.06 (m, 1 H). Stereochemistry arbitrarily assigned. Example 88: Methyl N-[(1R)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxop yrimidin-2-yl]- 1-phenyl-3,4-dihydro-1H-isoquinolin-7-yl]carbamate [00481] ES MS M/Z = 524.3 [M+H] ⁺ , UPLC: 97%; ¹ H NMR (300 MHz, DMSO-d6) δ 10.55 (s, 1H), 9.48 (s, 1H), 7.94 – 7.87 (m, 2H), 7.53 – 7.44 (m, 2H), 7.27 – 7.05 (m, 8H), 5.95 (s, 1H), 3.58 (s, 3H), 3.54 (s, 4H), 3.20 (d, J = 10.4 Hz, 2H), 2.91 – 2.87 (m, 1H). Stereochemistry arbitrarily assigned. Example 89: Methyl N-[(1S)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxop yrimidin-2-yl]- 1-phenyl-3,4-dihydro-1H-isoquinolin-7-yl]carbamate [00482] ES MS M/Z = 524.3 [M+H] ⁺ , UPLC: 97%; ¹ H NMR (300 MHz, DMSO-d6) δ 10.55 (s, 1H), 9.48 (s, 1H), 7.94 – 7.87 (m, 2H), 7.53 – 7.44 (m, 2H), 7.27 – 7.05 (m, 8H), 5.95 (s, 1H), 3.58 (s, 3H), 3.54 (s, 4H), 3.20 (d, J = 10.4 Hz, 2H), 2.91 – 2.87 (m, 1H). Stereochemistry arbitrarily assigned. Example 90: (3R)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyri midin-2-yl]-3-phenyl- 1,3-dihydroisoindole-5-carboxylic acid [00483] ES MS M/Z = 481.15 [M+H] ⁺ . UPLC: 92%, ¹ H NMR (400 MHz, DMSO-d6) δ 7.91 (q, J = 9.6, 8.7 Hz, 3H), 7.69 - 7.40 (m, 6H), 7.33-7.24 (t, J = 7.4 Hz, 3H), 6.80 (s, 1H), 5.49 (d, J = 14.7 Hz, 1H), 4.77 (d, J = 14.8 Hz, 1H), 3.60 (s, 3H), 1.24 (s, 2H). Stereochemistry arbitrarily assigned. Example 91: (3S)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyri midin-2-yl]-3-phenyl- 1,3-dihydroisoindole-5-carboxylic acid [00484] ES MS M/Z = 481.15 [M+H] ⁺ , UPLC: 92%; ¹ H NMR (400 MHz, DMSO-d6) δ 7.91 (q, J = 9.6, 8.7 Hz, 3H), 7.69 - 7.40 (m, 6H), 7.33-7.24 (t, J = 7.4 Hz, 3H), 6.80 (s, 1H), 5.49 (d, J = 14.7 Hz, 1H), 4.77 (d, J = 14.8 Hz, 1H), 3.60 (s, 3H), 1.24 (s, 2H). Stereochemistry arbitrarily assigned. Example 92: 2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyrimidin -2-yl]-1-(2- cyanophenyl)-3,4-dihydro-1H-isoquinoline-7-carboxylic acid [00485] Step 1: The mixture of methyl 2-[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6- oxopyrimidin-2-yl]-1-(2-chlorophenyl)-3,4-dihydro-1H-isoquin oline-7-carboxylate (300 mg, 0.539 mmol, 1 equiv), Zn (7 mg, 0.102 mmol, 0.19 equiv), Zn(CN)2 (35 mg, 0.302 mmol, 0.56 equiv), Pd(TFA)2 (35 mg, 0.108 mmol, 0.2 equiv), TRIXIEPHOS (85 mg, 0.216 mmol, 0.4 equiv) was added in DMA (8 mL) under a nitrogen atmosphere. The mixture was stirred at 100 °C for 16 h. The mixture was diluted with H2O (30 mL) and extracted with DCM (20 mL x 3). The organic layer was combined, washed by brine, dried over sodium sulfate, filtered, and concentrated. The residue was purified by reversed-phase flash chromatography (column, C18 silica gel; mobile phase, acetonitrile in Water (0.05% TFA), 20% to 80% gradient in 30 min; detector, UV 254 nm) to afford methyl 2-[4-(1,3-benzoxazol-2- yl)-5-methoxy-1-methyl-6-oxopyrimidin-2-yl]-1-(2-cyanophenyl )-3,4-dihydro-1H-isoquinoline-7- ^{carboxylate (200 mg, 67.81%) as colorless solid. ES MS M/Z = 548.4 [M+H]+.} [00486] Step 2: To the mixture of methyl 2-[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6- oxopyrimidin-2-yl]-1-(2-cyanophenyl)-3,4-dihydro-1H-isoquino line-7-carboxylate (200 mg, 0.365 mmol, 1 equiv) in DMF (5 mL) was added LiBr (190 mg, 2.19 mmol, 6 equiv). The mixture was stirred at 100 °C for 16 h. The mixture was diluted with H ₂ O (30 ml) and extracted with DCM/MeOH (10:1) (20 mL x 3). The organic layer was combined, washed with brine, dried over sodium sulfate, filtered, and concentrated to afford methyl (1S)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyri midin-2- yl]-1-(2-cyanophenyl)-3,4-dihydro-1H-isoquinoline-7-carboxyl ate (100 mg, 51.31%). ES MS M/Z = 534.3 [M+H] ⁺ . [00487] Step 3: To the mixture of methyl (1S)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6- oxopyrimidin-2-yl]-1-(2-cyanophenyl)-3,4-dihydro-1H-isoquino line-7-carboxylate (100 mg, 0.187 mmol, 1 equiv) in THF (4 mL) and MeOH (2 mL) was added LiOH (27 mg, 1.122 mmol, 6 equiv) in H ₂ O (2 mL). The mixture was stirred at ambient temperature for 48 h. The mixture was acidified to pH 3 with HCl (2 M). The mixture was concentrated to remove THF and MeOH. The aqueous layer was extracted with DCM/MeOH (10:1). The organic layer was combined, washed by brine, dried over sodium sulfate, filtered, and concentrated. The crude product was purified by reversed-phase flash chromatography (column, C18 silica gel; mobile phase, acetonitrile in water (0.05% FA), 10% to 50% gradient in 30 min; detector, UV 254 nm) to afford 2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6- oxopyrimidin-2-yl]-1-(2-cyanophenyl)-3,4-dihydro-1H-isoquino line-7-carboxylic acid (5.4 mg, 5.47%). ES MS M/Z = 520.2 [M+H] ⁺ . UPLC:98%; ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 12.91 (br, 1H), 10.57 (br, 1H), 7.89 - 7.85 (m, 2H), 7.79 – 7.72 (m, 2H), 7.67 (d, J = 7.9 Hz, 1H), 7.57 - 7.52 (m, 2H), 7.49 – 7.30 (m, 4H), 6.34 (s, 1H), 3.74 (d, J = 12.3 Hz, 1H), 3.62 (s 3H), 3.56 - 3.45 (m, 1H), 3.32 - 3.19 (m, 1H), 3.02 (d, J = 16.7 Hz, 1H). [00488] Purification by chiral HPLC provided the following compounds: Example 162: (R)-2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2- yl)-1-(2-cyanophenyl)-1,2,3,4-tetrahydroisoquinoline-7-carbo xylic acid [00489] ES MS M/Z = 520.2 [M+H] ⁺ , UPLC: 98%; ¹ H NMR (300 MHz, DMSO-d6) δ 12.91 (br, 1H), 10.57 (br, 1H), 7.89 - 7.85 (m, 2H), 7.79 – 7.72 (m, 2H), 7.67 (d, J = 7.9 Hz, 1H), 7.57 - 7.52 (m, 2H), 7.49 – 7.30 (m, 4H), 6.34 (s, 1H), 3.74 (d, J = 12.3 Hz, 1H), 3.62 (s 3H), 3.56 - 3.45 (m, 1H), 3.32 - 3.19 (m, 1H), 3.02 (d, J = 16.7 Hz, 1H). Stereochemistry arbitrarily assigned. Example 163: (S)-2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2- yl)-1-(2-cyanophenyl)-1,2,3,4-tetrahydroisoquinoline-7-carbo xylic acid [00490] ES MS M/Z = 520.2 [M+H] ⁺ , UPLC: 98%; ¹ H NMR (300 MHz, DMSO-d6) δ 12.91 (br, 1H), 10.57 (br, 1H), 7.89 - 7.85 (m, 2H), 7.79 – 7.72 (m, 2H), 7.67 (d, J = 7.9 Hz, 1H), 7.57 - 7.52 (m, 2H), 7.49 – 7.30 (m, 4H), 6.34 (s, 1H), 3.74 (d, J = 12.3 Hz, 1H), 3.62 (s 3H), 3.56 - 3.45 (m, 1H), 3.32 - 3.19 (m, 1H), 3.02 (d, J = 16.7 Hz, 1H). Stereochemistry arbitrarily assigned. Example 93: (S)-2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2-yl)- 1-(o-tolyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxylic acid [00491] Step 1: A solution of 2-(4-bromophenyl)ethanamine (10 g, 49.980 mmol, 1 equiv), 2- methylbenzoyl chloride (7.73 g, 49.980 mmol, 1 equiv) and NaOH (3.20 g, 79.968 mmol, 1.6 equiv) in DCM (150 mL) and H2O (40 mL). The mixture was stirred for 20 min at 0 °C. The mixture was acidified to pH 6 with HCl (1 M). The aqueous layer was extracted with DCM (3 x 50 mL). The crude product was re-crystallized from DCM/Hex (1:2) (200 mL) to afford N-[2-(3-bromophenyl)ethyl]-2-methylbenzamide (14.1 g, 75.4%) as a yellow solid. ES MS M/Z = 319.3 [M+H] ⁺ . [00492] Step 2: A solution of N-[2-(3-bromophenyl)ethyl]-2-methylbenzamide (12 g, 37.710 mmol, 1 equiv) in polyphosphoric acid (200 mL) was stirred for 4 h at 165 °C. The reaction was quenched with H ₂ O at 0 °C. The mixture was basified to pH 8 with NaOH. The resulting mixture was extracted with EA (3 x 150 mL). The combined organic layers and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with EA/PE (1:1) to afford 7-bromo-1-(2-methylphenyl)-3,4- dihydroisoquinoline (3.7 g, 30.9%) as a yellow solid. ES MS M/Z = 301.2 [M+H] ⁺ . [00493] Step 3: A solution of 7-bromo-1-(2-methylphenyl)-3,4-dihydroisoquinoline (5.6 g, 18.654 mmol, 1 equiv) in MeOH (80 mL) was added NaBH4 (3.53 g, 93.270 mmol, 5 equiv) at 0 °C. The mixture was stirred for 2 h at 0 °C. The reaction was quenched by the addition of NH4Cl (100 mL) at 0 °C. The resulting mixture was extracted with EA (3 x 100mL). The combined organic layers dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The product was precipitated by the addition of hydrochloric acid 4.0 M Solution In ethyl acetate (300 mL) to afford 7-bromo-1-(2-methylphenyl)-1,2,3,4-tetrahydroisoquinoline (2.9 g, 47.79%) as a colorless solid. ES MS M/Z = 301.1 [M+H] ⁺ . [00494] Step 4: A solution of 7-bromo-1-(2-methylphenyl)-1,2,3,4-tetrahydroisoquinoline (2.91 g, 9.629 mmol, 1 equiv) in DCM (40 mL) was added Boc ₂ O (3.15 g, 14.4 mmol, 1.5 equiv) and Et ₃ N (4.38 g, 43.3 mmol, 4.5 equiv). The mixture was stirred for 2 h at 20 °C. The resulting mixture was extracted with DCM (3 x 20 mL). The combined organic layers were dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure to afford tert-butyl 7-bromo-1-(2- methylphenyl)-3,4-dihydro-1H-isoquinoline-2-carboxylate (3.5 g, 75%) as a yellow solid. ES MS M/Z = 403.4 [M+H] ⁺ . [00495] Step 5: A solution of tert-butyl 7-bromo-1-(2-methylphenyl)-3,4-dihydro-1H-isoquinoline-2- carboxylate (3.5 g, 8.699 mmol, 1 equiv) in CH3OH (100 mL) was added Pd(dppf)Cl2 (0.95 g, 1.305 mmol, 0.15 equiv) and Et ₃ N (4.40 g, 43.495 mmol, 5 equiv). The mixture was stirred for 16 h at 130 °C under CO (20 atm) atmosphere. The resulting mixture was filtered; the filter cake was washed with CH3OH (3 x 20 mL). The filtrate was concentrated under reduced pressure. The resulting mixture was extracted with EA (3 x 20 mL). The combined organic layers and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with EA/PE (1:1) to afford 2-tert-butyl 7-methyl 1-(2-methylphenyl)- 3,4-dihydro-1H-isoquinoline-2,7-dicarboxylate (1.7 g, 51%) as a yellow solid. ES MS M/Z = 382.2 [M+H] ⁺ . [00496] Step 6: The crude product was purified by PREP_SFC with the following conditions: Column: UnichiralOD-5H 4.6*100mm, 5μm; Mobile Phase B: IPA (0.1%DEA); Flow rate: 4 mL/min; Gradient: isocratic% B. The resulting product was dried with a rotary evaporator, and gradient to afford 2-(tert- butyl) 7-methyl (S)-1-(o-tolyl)-3,4-dihydroisoquinoline-2,7(1H)-dicarboxylat e (400 mg, 24%). ES MS M/Z = 382.5 [M+H] ⁺ . [00497] Step 7: A solution of 2-(tert-butyl) 7-methyl (S)-1-(o-tolyl)-3,4-dihydroisoquinoline-2,7(1H)- dicarboxylate (400 mg, 1.049 mmol, 1 equiv) in 4M HCl in dioxane (10 mL). The mixture was stirred for 2 h at 20 °C. The resulting mixture was concentrated under reduced pressure to afford methyl (S)-1-(o- tolyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxylate (260 mg, 86%) as a yellow solid. ES MS M/Z = 282.4 [M+H] ⁺ . [00498] Step 8: A solution of methyl (S)-1-(o-tolyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxylate (245 mg, 0.871 mmol, 1 equiv), 6-(1,3-benzoxazol-2-yl)-2-chloro-5-methoxy-3-methylpyrimidin -4-one (330 mg, 1.132 mmol, 1.3 equiv) and CsF (145 mg, 0.958 mmol, 1.1 equiv) in DMSO (8 mL) was stirred for 16 h at 80 °C. The resulting mixture was extracted with EA (3 x 10 mL). The combined organic layers were dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with EA/PE (1:1) to afford methyl (S)-2-(4-(benzo[d]oxazol-2-yl)-5-methoxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2-yl)-1- (o-tolyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxylate (140 mg, 29%) as a yellow solid. ES MS M/Z = 537.6 [M+H] ⁺ . [00499] Step 9: A solution of methyl (S)-2-(4-(benzo[d]oxazol-2-yl)-5-methoxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2-yl)-1-(o-tolyl)-1,2,3,4-tetrahydroisoquin oline-7-carboxylate (140 mg, 0.261 mmol, 1 equiv) in DMF (8 mL) was added LiBr (227 mg, 2.610 mmol, 10 equiv). The mixture was stirred for 16 h at 100 °C. The residue was purified by trituration with H2O (10 mL). The precipitated solids were collected by filtration and washed with MeOH (2 x 5 mL) to afford methyl (S)-2-(4-(benzo[d]oxazol-2- yl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidin-2-yl)-1-(o -tolyl)-1,2,3,4-tetrahydroisoquinoline-7- carboxylate (130 mg, 86%) as a yellow solid. ES MS M/Z = 368.2 [M+H] ⁺ . [00500] Step 10: A solution of methyl (S)-2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2-yl)-1-(o-tolyl)-1,2,3,4-tetrahydroisoquin oline-7-carboxylate (130 mg, 0.249 mmol, 1 equiv) in MeOH (0.5 mL), THF (2 mL) and H2O (1.5 mL) was added LiOH (36 mg, 1.494 mmol, 6 equiv). The mixture was stirred for 5 h at 40 °C. The resulting mixture was concentrated under reduced pressure. The resulting mixture was diluted with H ₂ O (5 mL). The residue was acidified to pH 4 with HCl. The precipitated solids were collected by filtration and to afford (S)-2-(4-(benzo[d]oxazol-2-yl)-5- hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidin-2-yl)-1-(o-tolyl )-1,2,3,4-tetrahydroisoquinoline-7- carboxylic acid (12.5 mg, 9.8%). ES MS M/Z = 509.2 [M+H] ⁺ , UPLC: 99%; ¹ H NMR (300 MHz, DMSO-d6) δ 7.86 - 7.85 (m, 2H), 7.73-7.70 (m, 1H), 7.70 - 7.44 (m, 2H), 7.37 - 7.35 (m, 1H), 7.29 - 7.26 (s, 1H), 7.20 - 7.18 (m, 2H), 7.10 - 6.97 (m, 2H), 6.22 (s, 1H), 3.65 - 3.54 (m, 5H), 3.46 – 3.21 (s, 1H), 3.19 – 2.96 (m, 1H), 2.58 - 2.50 (s, 3H). [00501] The following compounds were synthesized in a similar manner: Example 100: (1R)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyri midin-2-yl]-1-(2- methylphenyl)-3,4-dihydro-1H-isoquinoline-7-carboxylic acid [00502] ES MS M/Z = 509.2 [M+H] ⁺ , UPLC: 99%; ¹ H NMR (300 MHz, DMSO-d6) δ 12.78 (s, 1H), 10.56 (s, 1H), 7.86 (d, J = 7.2 Hz, 2H), 7.73 (d, J=7.8 Hz, 1H), 7.59 - 7.43 (m, 2H), 7.38 (d, J=8.1 Hz, 1H), 7.30 (s, 1H), 7.25-7.14 (m, 1H), 7.12 – 7.05 (m, 1H), 7.04 – 6.95 (m, 2H), 6.23(s, 1H), 3.71 - 3.51 (m, 4H), 3.49-3.37 (m, 1H),3.32 (s, 1H), 3.27-3.21 (m, 1H), 2.98(d, J=5.7Hz, 1H), 2.58(s, 3H). Stereochemistry arbitrarily assigned. Example 101: (R)-2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2- yl)-1-(2-fluorophenyl)-1,2,3,4-tetrahydroisoquinoline-7-carb oxylic acid [00503] ES MS M/Z =513.10 [M+H]+, UPLC: 98%; ¹ H NMR (400 MHz, DMSO-d6) δ 8.81 - 8.51 (m, 1 H), 7.89 - 7.69 (m, 2 H), 7.50 - 7.42 (m, 1 H), 7.41 – 7.35 (m, 1 H), 7.31 - 7.21 (m, 3 H), 7.20 - 7.11 (m, 1 H), 7.09 – 6.99 (m, 2 H), 6.32 – 6.15 (m, 1 H), 3.56 - 3.50 (m, 4 H), 3.21 - 3.11 (m, 1 H), 3.19 - 3.03 (m, 1 H), 3.05 - 2.92 (m, 1 H). Stereochemistry arbitrarily assigned. Example 94: N-{2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyrimi din-2-yl]-1-phenyl-3,4- dihydro-1H-isoquinolin-7-yl}acetamide [00504] ES MS M/Z = 508.2 [M+H] ⁺ , UPLC: 98%; ¹ H NMR (300 MHz, DMSO-d6) δ 9.77 (s, 1H), 8.35 – 8.25 (m, 1H), 8.06 – 8.01 (m, 1H), 7.45 - 7.43 (m, 3H), 7.36 – 7.27 (m, 3H), 7.18 – 7.16 (m, 3H), 7.10 – 7.07 (m, 1H), 7.01 (s, 1H), 5.89 (s, 1H), 3.77 (s, 3H), 3.16 – 3.04 (m, 2H), 2.95 - 2.88 (m, 2H), 1.93 (s, 3H). Example 95: (1S)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyri midin-2-yl]-1-(2- chlorophenyl)-3,4-dihydro-1H-isoquinoline-7-carboxamide [00505] ES MS M/Z = 528.1 [M+H] ⁺ , UPLC: 98%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.25 (s, 1H), 7.92 - 7.87 (m, 1H), 7.80 - 7.65 (m, 2H), 7.48 - 7.28 (m, 5H), 7.17 - 7.11 (m, 1H), 6.42 - 6.39 (m, 1H), 3.69 - 63.55 (m, 6H), 3.17 - 2.97 (m, 2H). Stereochemistry arbitrarily assigned. Example 96: (1R)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyri midin-2-yl]-1- cyclopentyl-3,4-dihydro-1H-isoquinoline-6-carboxylic acid _[00506] ES MS M/Z = 487.2 [M+H] ⁺ , UPLC: 99%; ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 7.91 – 7.80 (m, 2H), 7.79 - 7.72 (m, 2H), 7.55 – 7.39 (m, 3H), 4.69 (d, J = 8.8 Hz, 1H), 3.76 - 3.66 (m, 2H), 3.34 (s, 3H), 3.13 – 2.89 (m, 2H), 2.33 - 2.28 (m, 1H), 1.79 - 1.77 (m, 1H), 1.60- 1.31 (m, 6H), 1.28 - 1.17 (m, 1H). Stereochemistry arbitrarily assigned. Example 160: (S)-N-{2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopy rimidin-2-yl]-1- phenyl-3,4-dihydro-1H-isoquinolin-7-yl}acetamide [00507] ES MS M/Z = 508.2 [M+H] ⁺ , UPLC: 98%; ¹ H NMR (300 MHz, DMSO-d6) δ 9.77 (s, 1H), 8.35 – 8.25 (m, 1H), 8.06 – 8.01 (m, 1H), 7.45 - 7.43 (m, 3H), 7.36 – 7.27 (m, 3H), 7.18 – 7.16 (m, 3H), 7.10 – 7.07 (m, 1H), 7.01 (s, 1H), 5.89 (s, 1H), 3.77 (s, 3H), 3.16 – 3.04 (m, 2H), 2.95 - 2.88 (m, 2H), 1.93 (s, 3H). Stereochemistry arbitrarily assigned. Example 161: (S)-N-{2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopy rimidin-2-yl]-1- phenyl-3,4-dihydro-1H-isoquinolin-7-yl}acetamide [00508] ES MS M/Z = 508.2 [M+H] ⁺ , UPLC: 98%; ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 9.77 (s, 1H), 8.35 – 8.25 (m, 1H), 8.06 – 8.01 (m, 1H), 7.45 - 7.43 (m, 3H), 7.36 – 7.27 (m, 3H), 7.18 – 7.16 (m, 3H), 7.10 – 7.07 (m, 1H), 7.01 (s, 1H), 5.89 (s, 1H), 3.77 (s, 3H), 3.16 – 3.04 (m, 2H), 2.95 - 2.88 (m, 2H), 1.93 (s, 3H). Stereochemistry arbitrarily assigned. Example 118: (S)-2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2- yl)-1-cyclopentyl-1,2,3,4-tetrahydroisoquinoline-6-carboxyli c acid [00509] ES MS M/Z = 487.1 [M+H] ⁺ , UPLC: 99%; ¹ H NMR (300 MHz, DMSO-d6) δ 12.84 (s, 1H), 10.44 (s, 1H), 7.91 – 7.82 (m, 2H), 7.87 – 7.71 (m, 2H), 7.54 – 7.38 (m, 3H), 4.69 (d, J = 8.8 Hz, 1H), 3.75 – 3.64 (m, 2H), 3.69 (s, 3H), 3.13 – 2.89 (m, 2H), 2.36 - 2.33 (m, 1H), 1.79 - 1.61 (m, 1H), 1.58 - 1.51 (m, 2H), 1.43 (d, J = 6.4 Hz, 4H), 1.25 - 1.21 (m, 1H). Example 97: Methyl N-{2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyrimi din-2-yl]-1- phenyl-3,4-dihydro-1H-isoquinolin-7-yl}carbamate [00510] Step 1: To a stirred solution of 6-(1,3-benzoxazol-2-yl)-2-(7-bromo-1-phenyl-3,4-dihydro-1H- isoquinolin-2-yl)-5-methoxy-3-methylpyrimidin-4-one (200 mg, 0.368 mmol, 1 equiv) and methyl carbamate (33 mg, 0.442 mmol, 1.2 equiv) in 1,4-dioxane (5 mL) were added Pd2(dba)3 (16 mg, 0.018 mmol, 0.05 equiv), Cs2CO3 (239 mg, 0.736 mmol, 2 equiv) and XantPhos (21 mg, 0.037 mmol, 0.1 equiv) in portions at ambient temperature under nitrogen atmosphere. The resulting mixture was stirred overnight at 100 °C under a nitrogen atmosphere. The reaction was monitored by LCMS. The resulting mixture was filtered; the filter cake was washed with EtOAc (3 x 20 mL). The filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography (column, C18 silica gel; mobile phase, acetonitrile in Water (10mmol/L NH ₄ HCO ₃ ), 10% to 50% gradient in 10 min; detector, UV 254 nm). This resulted in N-{2-[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6- oxopyrimidin-2-yl]-1-phenyl-3,4-dihydro-1H-isoquinolin-7-yl} acetamide (160 mg, 77%) as a colorless solid. ES MS M/Z = 538.25 [M+H] ⁺ . [00511] Step 2: A solution of methyl N-{2-[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6- oxopyrimidin-2-yl]-1-phenyl-3,4-dihydro-1H-isoquinolin-7-yl} carbamate (60 mg, 0.112 mmol, 1 equiv) and LiBr (58 mg, 0.672 mmol, 6 equiv) in DMF (1.00 mL) was stirred overnight at 80 °C under nitrogen atmosphere. The reaction was monitored by LCMS. The residue was purified by reversed-phase flash chromatography (column, C18 silica gel; mobile phase, acetonitrile in Water (0.1% FA), 10% to 50% gradient in 10 min; detector, UV 254 nm). This resulted in formic acid; methyl N-{2-[4-(1,3-benzoxazol- 2-yl)-5-hydroxy-1-methyl-6-oxopyrimidin-2-yl]-1-phenyl-3,4-d ihydro-1H-isoquinolin-7-yl} carbamate (14.2 mg, 22%). ES MS M/Z = 524.20 [M+H] ⁺ , UPLC: 97%; ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 9.47 (s, 1H), 7.95 – 7.80 (m, 1H), 7.51 – 7.36 (m, 2H), 7.36 – 7.25 (m, 4H), 7.17 – 7.14 (m, 1H), 7.00 (s, 1H), 5.89 (s, 1H), 3.58 (s, 3H), 3.38 – 3.21 (m, 4H), 3.12 – 3.08 (m, 2H), 2.89 – 2.72 (m, 1H). [00512] The following compound was synthesized in a similar manner: Example 98: N-{2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyrimi din-2-yl]-1-phenyl-3,4- dihydro-1H-isoquinolin-7-yl}-N-methylacetamide [00513] ES MS M/Z = 522.25 [M+H] ⁺ , UPLC: 99%; ¹ H NMR (300 MHz, DMSO-d ₆ ) δ8.05 – 7.98 (m, 1H), 7.96 – 7.79 (m, 1H), 7.40 - 7.24 (m, 5H), 7.21 – 7.09 (m, 4H), 6.64 (s, 1H), 5.94 (s, 1H), 3.64 – 3.59 (m, 2H), 3.52 (s, 3H), 3.24 – 3.16 (m, 2H), 3.01 (s, 3H), 1.23 (s, 3H). Example 99: (R)-2-(4-(5,6-dihydro-4H-cyclopenta[d]oxazol-2-yl)-5-hydroxy -1-methyl-6-oxo-1,6- dihydropyrimidin-2-yl)-1-phenyl-1,2,3,4-tetrahydroisoquinoli ne-6-carboxylic acid

[00514] Step 1: A solution of tert-butyl N-(2-oxocyclopentyl) carbamate (10 g, 50.188 mmol, 1 equiv) in HCl(gas) in 1,4-dioxane (100 mL) was stirred for 30 min at ambient temperature in an open flask. The reaction was monitored by TLC. The resulting mixture was concentrated under reduced pressure. This resulted in 2-aminocyclopentan-1-one (5 g, 101%) as a colorless solid. The crude product was used in the next step directly without further purification. [00515] Step 2: To a stirred solution of 2-aminocyclopentan-1-one hydrochloride (5 g, 36.9 mmol, 1 equiv) and 2-chloro-5-methoxy-6-oxo-1H-pyrimidine-4-carboxylic acid (9.05 g, 44.3 mmol, 1.2 equiv) in DCM (60 mL) were added DIEA (28.60 g, 221.3 mmol, 6 equiv) and T ₃ P (140.8 g, 221.3 mmol, 6 equiv, 50%) dropwise at ambient temperature under air atmosphere. The reaction was monitored by LCMS. The resulting mixture was diluted with water (50 mL). The resulting mixture was extracted with DCM (2 x 50 mL). The combined organic layers were washed with water (3 x 50 mL) and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure to provide 2-chloro- 5-methoxy-6-oxo-N-(2-oxocyclopentyl)-1H-pyrimidine-4-carboxa mide (5 g, 47.46%) as a brown solid. The crude product was used in the next step directly without further purification. ES MS M/Z = 286.1 [M+H] ⁺ . [00516] Step 3: To a stirred solution 2-chloro-5-methoxy-6-oxo-N-(2-oxocyclopentyl)-1H-pyrimidine- 4-carboxamide (5 g, 17.502 mmol, 1 equiv) and MeI (2.7 mL, 43.755 mmol, 2.5 equiv) in DMF (50 mL, 646.1 mmol, 36.91 equiv) was added Cs2CO3 (17.1 g, 52.5 mmol, 3 equiv) in portions at ambient temperature under air atmosphere. The resulting mixture was stirred for 30 min at ambient temperature under air atmosphere. The resulting mixture was filtered, and the filter cake was washed with EtOAc (2 x 20 mL). The filtrate was concentrated under reduced pressure. The residue was purified by reversed- phase flash chromatography (column, C18 silica gel; mobile phase, acetonitrile in Water (0.1% FA), 10% to 50% gradient in 10 min; detector, UV 254 nm). This provided 2-chloro-5-methoxy-1-methyl-6-oxo-N- (2-oxocyclopentyl) pyrimidine-4-carboxamide (1.5 g, 25%) as a light yellow solid. ES MS M/Z = 300.1 [M+H] ⁺ . [00517] Step 4: To a stirred solution of 2-chloro-5-methoxy-1-methyl-6-oxo-N-(2-oxocyclopentyl) pyrimidine-4-carboxamide (700 mg, 2.34 mmol, 1 equiv) and methyl (1R)-1-phenyl-1,2,3,4- tetrahydroisoquinoline-7-carboxylate (624 mg, 2.336 mmol, 1 equiv) in DMSO (5 mL, 84.39 equiv) was added CsF (390 mg, 2.570 mmol, 1.1 equiv) dropwise at ambient temperature under air atmosphere. The resulting mixture was stirred overnight at 80 °C under nitrogen atmosphere. The reaction was monitored by LCMS. The resulting mixture was filtered, the filter cake was washed with EtOAc (2 x 20 mL). The filtrate was concentrated under reduced pressure. The crude product was re-crystallized from diethyl ether (20 mL) to afford methyl (1R)-2-{5-methoxy-1-methyl-6-oxo-4-[(2-oxocyclopentyl) carbamoyl] pyrimidin-2-yl}-1-phenyl-3,4-dihydro-1H-isoquinoline-7-carbo xylate as a light yellow solid. ES MS M/Z = 531.15 [M+H] ⁺ . [00518] Step 5: To a stirred solution methyl (1R)-2-{5-methoxy-1-methyl-6-oxo-4-[(2-oxocyclopentyl) carbamoyl] pyrimidin-2-yl}-1-phenyl-3,4-dihydro-1H-isoquinoline-7-carbo xylate (300 mg, 0.565 mmol, 1 equiv) and hexachloroethane (334 mg, 1.412 mmol, 2.5 equiv) in DCM (5 mL) was added triethylamine (1.2 mL, 3.39 mmol, 6 equiv) and triphenylphosphine (444 mg, 1.70 mmol, 3 equiv) dropwise at ambient temperature under nitrogen atmosphere. The resulting mixture was stirred overnight at ambient temperature under nitrogen atmosphere. The resulting mixture was concentrated under vacuum. The residue was purified by reversed-phase flash chromatography (column, C18 silica gel; mobile phase, acetonitrile in Water (10mmol/L NH4HCO3), 10% to 50% gradient in 10 min; detector, UV 254 nm). This resulted in methyl (1R)-2-(4-{4H,5H,6H-cyclopenta[d] [1,3] oxazol-2-yl}-5-methoxy- 1-methyl-6-oxopyrimidin-2-yl)-1-phenyl-3,4-dihydro-1H-isoqui noline-7-carboxylate as a colorless solid. ES MS M/Z = 513.2 [M+H] ⁺ . [00519] Step 6: A solution of methyl (1R)-2-(4-{4H,5H,6H-cyclopenta[d] [1,3] oxazol-2-yl}-5- methoxy-1-methyl-6-oxopyrimidin-2-yl)-1-phenyl-3,4-dihydro-1 H-isoquinoline-7-carboxylate (140 mg, 0.273 mmol, 1 equiv) and LiBr (142.3 mg, 1.64 mmol, 6 equiv) in DMF (2 mL) was stirred for overnight at 80 °C under nitrogen atmosphere. The resulting mixture was diluted with water (10 mL). The precipitated solids were collected by filtration and washed with water (2 x 30 mL). The residue was purified by reversed-phase flash chromatography (column, C18 silica gel; mobile phase, acetonitrile in Water (10mmol/L NH4HCO3), 10% to 50% gradient in 10 min; detector, UV 254 nm). This provided methyl (1R)-2-(4-{4H,5H,6H-cyclopenta[d] [1,3] oxazol-2-yl}-5-hydroxy-1-methyl-6-oxopyrimidin-2- yl)-1-phenyl-3,4-dihydro-1H-isoquinoline-7-carboxylate (100 mg, 66.09%) as a colorless solid. ES MS M/Z = 499.2 [M+H] ⁺ . [00520] Step 7: To a stirred mixture of methyl (1R)-2-(4-{4H,5H,6H-cyclopenta[d] [1,3] oxazol-2-yl}- 5-hydroxy-1-methyl-6-oxopyrimidin-2-yl)-1-phenyl-3,4-dihydro -1H-isoquinoline-7-carboxylate (80 mg, 0.16 mmol, 1 equiv) in THF (2 mL) and MeOH (1 mL) was added LiOH (2M aq.) (0.80 mL, 1.60 mmol, 9.97 equiv) dropwise at ambient temperature under air atmosphere. The resulting mixture was stirred for 1 h at 40 °C under air atmosphere. The reaction was monitored by LCMS. The resulting mixture was concentrated under reduced pressure. The mixture was acidified to pH 5 with HCl (aq.). The aqueous layer was extracted with CH3Cl (3 x 30 mL), dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography (column: C18 silica gel; mobile phase, acetonitrile in Water (10mmol/L NH4HCO3), 10% to 50% gradient in 10 min; detector, UV 254 nm). This provided (1R)-2-(4-{4H,5H,6H- cyclopenta[d] [1,3] oxazol-2-yl}-5-hydroxy-1-methyl-6-oxopyrimidin-2-yl)-1-pheny l-3,4-dihydro-1H- isoquinoline-7-carboxylic acid (9.4 mg, 11.9%). ES MS M/Z = 485.2 [M+H] ⁺ , UPLC: 98%; ¹ H NMR (300 MHz, DMSO-d6) δ 7.74 (dd, J = 7.9, 1.7 Hz, 1H), 7.46 (d, J = 1.8 Hz, 1H), 7.37 (d, J = 8.1 Hz, 1H), 7.24 – 7.12 (m, 5H), 5.99 (s, 1H), 3.52 (s, 4H), 3.26 – 3.21 (m, 2H), 3.08 – 3.02 (m, 1H), 2.83 (s, 3H), 2.58 – 2.51 (m, 4H). Example 102: (1R,4S)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxop yrimidin-2-yl]-4- methyl-1-phenyl-3,4-dihydro-1H-isoquinoline-6-carboxylic acid [00521] Step 1: To a solution of methyl isoquinoline-6-carboxylate (10 g, 53.419 mmol), NBS (14.26 g, 80.129 mmol) in AcOH (202 mL) giving a brown suspension, which was stirred at 80 ℃ overnight. After concentration, the obtained residue was extracted with ethyl acetate (10 mL x 3). The combined organic layers were washed with saturated sodium sulfite (5 mL X 3), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography, eluted with PE / EA (10:1) to afford methyl 4-bromoisoquinoline-6-carboxylate as a yellow solid (10 g, 70% yield). ES MS M/Z = 267.95 [M+H] ⁺ . [00522] Step 2: To a solution of methyl 4-bromoisoquinoline-6-carboxylate (8 g, 30.065 mmol), methylboronic acid (3.60 g, 60.1 mmol), Pd(dppf)Cl ₂ (2.20 g, 3.01 mmol), Cs ₂ CO ₃ (19.6 g, 60.1 mmol) in 1,4-dioxane/H2O (80/8 mL) was added giving a red suspension, which stirred at 110 ℃ under N2 for 2 h. After concentration, the resulting mixture was extracted with ethyl acetate (50 mL X 3). The combined organic layers were washed with brine (50 mL X 3), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford methyl 4-methylisoquinoline-6-carboxylate as a brown solid (5 g, 83% yield). ES MS M/Z = 202.10 [M+H] ⁺ . [00523] Step 3: A solution of methyl 4-methylisoquinoline-6-carboxylate (5 g) in DCM (150 mL) was stirred at ambient temperature for 5 min. To this suspension, m-CPBA (8.2 g) was added and stirred at ambient temperature overnight. After addition, the mixture was stirred at 0 °C and quenched with Na ₂ SO ₃ (aq.30 mL). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by trituration with DCM (30mL). The resulting mixture was concentrated under reduced pressure to afford 6-(methoxycarbonyl)-4-methyl-2-oxo-1,2- dihydroisoquinolin-2-ium as a yellow solid (4.8 g). ES MS M/Z = 218.05 [M+H] ⁺ . [00524] Step 4: A solution of the N-oxide (4.5 g, 58.5 mL) in phosphorus(V) oxychloride (5.0 mL, 53.48 mmol) was stirred at 60 °C for 1 h. The excess of phosphorus(V) oxychloride was removed under reduced pressure. The residue was quenched with 2 N aqueous NaOH solution and then it was extracted three times with EA. The combined organic phases were washed with brine, dried over sodium sulfate, filtered, and evaporated to afford methyl 1-chloro-4-methylisoquinoline-6-carboxylate (3.8 g, 69.37% yield) as a yellow oil. ES MS M/Z = 235.95 [M+H] ⁺ . [00525] Step 5: To a solution of methyl 1-chloro-4-methylisoquinoline-6-carboxylate (3.7 g, 15.7mmol), phenyl boronic acid (3.83 g, 31.4mmol), Pd(dppf)Cl ₂ DCM (1.28 g, 1.57mmol), Cs ₂ CO ₃ (10.23 g, 31.4mmol) in 1,4-dioxane/H2O (37/3.7 mL) was added giving a red suspension, which stirred at 110 ℃ under N2 for 2 h. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, acetonitrile in Water (0.05% TFA), 5% to 50% gradient in 20 min; detector, UV 254 nm to afford methyl 4-methyl-1-phenylisoquinoline-6- carboxylate as a colorless solid (3.7 g, 84.98% yield). ES MS M/Z = 278.15 [M+H] ⁺ . [00526] Step 6: To a 100 mL pressure tank reactor was added methyl 4-methyl-1-phenylisoquinoline- 6-carboxylate (3.7 g, 13.342 mmol) in AcOH (66.6 mL). PtO2 (606 mg) was added, and the reaction mixture was stirred under hydrogen (3 atm) for 7 h at 25 ℃. The organic layers were concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (2:1) to afford methyl (1R,4S)-4-methyl-1-phenyl-1,2,3,4-tetrahydroisoquinoline-6-c arboxylate as a colorless solid (1.6 g). The residue was purified by reversed-phase flash chromatography (column, C18 silica gel; mobile phase, acetonitrile in Water (0.05% TFA), 5% to 50% gradient in 20 min; detector, UV 254 nm) to afford methyl 4-methyl-1-phenyl-1,2,3,4-tetrahydroisoquinoline-6-carboxyla te as a colorless solid (1 g, 26.64% yield). ES MS M/Z = 282.10 [M+H] ⁺ . [00527] Step 7: A solution of E-methyl 4-methyl-1-phenyl-1,2,3,4-tetrahydroisoquinoline-6- carboxylate (200 mg, 0.711 mmol), 6-(benzo[d]oxazol-2-yl)-2-chloro-5-methoxy-3-methylpyrimidin - 4(3H)-one (249 mg, 0.853 mmol), CsF (130 mg, 0.853 mmol) in DMSO (3.6 mL) was stirred at 80 ℃ for overnight. The reaction mixture was quenched with water (10 mL), the resulting mixture was extracted with ethyl acetate (3 x 10 mL). The combined organic layers were washed with brine (3 x 20 mL), dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography, eluted with PE / EA (2:1) to afford methyl 2-(4-(benzo[d]oxazol-2-yl)-5-methoxy-1- methyl-6-oxo-1,6-dihydropyrimidin-2-yl)-4-methyl-1-phenyl-1, 2,3,4-tetrahydroisoquinoline-6- carboxylate as a yellow solid (330 mg). ES MS M/Z = 537.35 [M+H] ⁺ . [00528] Step 8: A solution of methyl (1R,4S)-2-[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6- oxopyrimidin-2-yl]-4-methyl-1-phenyl-3,4-dihydro-1H-isoquino line-6-carboxylate (330 mg, 0.615 mmol), LiBr (534 mg, 6.150 mmol) in DMF (6.6 mL) was stirred at 100 °C for overnight. After cooling to ambient temperature, the mixture was added H ₂ O (20 mL). The mixture was extracted by EA (3 x 20 mL). The organic layers were concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (3:1) to afford methyl 2-(4-(benzo[d]oxazol-2-yl)-5- hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidin-2-yl)-4-methyl-1 -phenyl-1,2,3,4-tetrahydroisoquinoline- 6-carboxylate as a yellow solid (240 mg, 74.68% yield). ES MS M/Z = 537.35 [M+H] ⁺ . [00529] Step 9: To a solution of methyl (1R,4S)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6- oxopyrimidin-2-yl]-4-methyl-1-phenyl-3,4-dihydro-1H-isoquino line-6-carboxylate (50 mg, 0.574 mmol) and lithium hydroxide (41 mg, 1.7 mmol) at ambient temperature in water (3 mL) was added giving a brown suspension. To this suspension, THF (3 mL) was added which was stirred giving a yellow solution, which stirred at ambient temperature overnight. After concentration, the pH was adjusted to 5-6 by addition of HCl (aq.2 M). The obtained residue was extracted with ethyl acetate (3 x 10 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated to afford a yellow solid (60 mg). The solid was submitted to prep-HPLC with following conditions: Column: XBridge Prep OBD C18 Column, 30*150 mm, 5 μm; Mobile Phase A: Water(10 mmol/L NH4HCO3+0.1% NH3.H2O), Mobile Phase B: acetonitrile; Flow rate: 60 mL/min; Gradient: 13% B to 31% B in 10 min; Wavelength: 254/220 nm; RT(min): 9.17. Concentration afforded 2-[4-(1,3- benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyrimidin-2-yl]-4-m ethyl-1-phenyl-3,4-dihydro-1H- isoquinoline-6-carboxylic acid (2.7 mg, 0.92% yield). ES MS M/Z = 509.20 [M+H] ⁺ , UPLC: 99%; ¹ H NMR (400 MHz, DMSO-d6) δ 8.79 - 8.41 (s, 1H), 7.99 - 7.71 (m, 3H), 7.68 (s, 1H), 7.51 (s, 1H), 7.41 - 7.02 (m, 6H), 7.01 - 7.71 (m, 1H), 6.21 - 6.79 (m, 1H), 6.21 - 5.85 (m, 1H), 3.65 - 3.07 (m, 6H), 1.81 - 1.49 (m, 3H). Example 103: (S)-2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2- yl)-1-(2-fluorophenyl)-1,2,3,4-tetrahydroisoquinoline-7-carb oxylic acid [00530] Step 1: A solution of 2-(4-bromophenyl)ethanol (5 g, 24.868 mmol, 1 equiv) in DCE (65 mL, 821.1 mmol, 33.02 equiv) was treated with 2-fluorobenzonitrile (4.5 g, 37.3 mmol, 1.5 equiv) and 2- fluoropyridine (2.4 g, 24.87 mmol, 1 equiv) at ambient temperature followed by the addition of Tf ₂ O (14.03 g, 49.74 mmol, 2 equiv) dropwise at 0 ℃. The resulting mixture was concentrated under vacuum. The crude product 7-bromo-1-(2-fluorophenyl)-3,4-dihydroisoquinoline (10 g) was used in the next step directly without further purification. ES MS M/Z = 304.01 [M+H] ⁺ . [00531] Step 2: To a stirred solution of 7-bromo-1-(2-fluorophenyl)-3,4-dihydroisoquinoline (10 g, 32.88 mmol, 1 equiv) in MeOH (100 mL) was added NaBH ₄ (3.7 g, 98.63 mmol, 3 equiv) at 0 ℃. The resulting mixture was stirred for 2 h at ambient temperature. The resulting mixture was concentrated under vacuum. The crude product was re-crystallized from HCl/EA to afford 7-bromo-1-(2- fluorophenyl)-1,2,3,4-tetrahydroisoquinoline hydrochloride (4 g, 34%) as a colorless solid. ES MS M/Z = 306.2 [M+H] ⁺ . [00532] Step 3: A solution of 7-bromo-1-(2-fluorophenyl)-1,2,3,4-tetrahydroisoquinoline (4 g, 13.06 mmol, 1 equiv) in DCM (80 mL, 1258.4 mmol, 96.3 equiv) was treated with Et ₃ N (3.97 g, 39.19 mmol, 3 equiv) for 5 min at 0 ℃ followed by the addition of Boc2O (4.28 g, 19.60 mmol, 1.5 equiv). The resulting mixture was stirred for 2 h at ambient temperature. The resulting mixture was extracted with DCM (2 x 20 ml). The combined organic layers were washed with H ₂ O (3 x 50 ml), dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE:EA (1:1) to afford tert-butyl 7- bromo-1-(2-fluorophenyl)-3,4-dihydro-1H-isoquinoline-2-carbo xylate (3.38 g, 62.83%) as a colorless solid. ES MS M/Z = 406.30 [M+H] ⁺ . [00533] Step 4: A solution of tert-butyl 7-bromo-1-(2-fluorophenyl)-3,4-dihydro-1H-isoquinoline-2- carboxylate (3.38 g, 8.319 mmol, 1 equiv) in MeOH (170 mL) was treated with TEA (2.53 g, 24.96 mmol, 3 equiv) followed by the addition of Pd(dppf)Cl2 (913 mg, 1.248 mmol, 0.15 equiv). The resulting mixture was stirred overnight at 130 ℃ under CO (20atm). The resulting mixture was concentrated under vacuum. The residue was diluted with EA (50 mL) and water (50 mL). The aqueous phase was extracted with EA (30 mL X 2). The combined organic phases were washed with H2O (50 mL X 2), dried with sodium sulfate, filtered, and concentrated. The obtained residue was submitted to silica gel giving 2-tert- butyl 7-methyl 1-(2-fluorophenyl)-3,4-dihydro-1H-isoquinoline-2,7-dicarboxy late (1.9 g, 58%). ES MS M/Z = 386.20 [M+H] ⁺ . [00534] Step 5: A solution of 2-tert-butyl 7-methyl 1-(2-fluorophenyl)-3,4-dihydro-1H-isoquinoline- 2,7-dicarboxylate (1.9 g, 4.93 mmol, 1 equiv) in DCM (20 mL) was treated with 4 M HCl in dioxane (20 mL) for 1 h at ambient temperature. The resulting mixture was concentrated under vacuum. The residue was suspended in CHCl ₃ /i-PrOH (20 mL, v/v, 3/1) and basified to pH ~ 10 with NaOH (aq., 1 M). The mixture was separated, and the aqueous phase was extracted with CHCl3/i-PrOH (10 mL x 2, v/v, 3/1). The combined organic phases were washed with brine (30 mL X 3), dried with sodium sulfate, filtered, and concentrated to afford methyl 1-[(3E)-3-fluoropenta-1,3-dien-2-yl]-1,2,3,4-tetrahydroisoqu inoline-7- carboxylate (1.2 g, 86%) as a colorless oil. ES MS M/Z = 286.12 [M+H] ⁺ . [00535] Step 6: Methyl 1-[(3E)-3-fluoropenta-1,3-dien-2-yl]-1,2,3,4-tetrahydroisoqu inoline-7- carboxylate (1.2 g, 4.36 mmol, 1 equiv) was submitted to Prep-SFC with the following conditions: Column: NB_CHIRALPAK AD, 3*25 cm, 5 μm; Mobile Phase A: CO2, Mobile Phase B: MeOH: acetonitrile=2: 1; Flow rate: 100 mL/min; Gradient: isocratic 18% B; Column Temperature(℃): 35; Back Pressure(bar): 100; Wave Length: 254 nm; RT1(min): 2.52; RT2(min): 4.25; Sample Solvent: MeOH(0.1% 2M NH3-MeOH); Injection Volume: 2.5 mL). After concentration, the first fraction provided (1R)-1-(2-fluorophenyl)-1,2,3,4-tetrahydroisoquinoline-7-car boxylate a light yellow oil. ES MS M/Z = 286.12 [M+H] ⁺ . After concentration, the second fraction provided methyl (1S)-1-(2- fluorophenyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxylate as a light yellow oil. ES MS M/Z = 286.12 [M+H] ⁺ . [00536] Step 7: A yellow solution of methyl (1S)-1-(2-fluorophenyl)-1,2,3,4-tetrahydroisoquinoline-7- carboxylate (250 mg, 0.876 mmol, 1 equiv), 6-(1,3-benzoxazol-2-yl)-2-chloro-5-methoxy-3- methylpyrimidin-4-one (383 mg, 1.31 mmol, 1.5 equiv) and CsF (173 mg, 1.14 mmol, 1.3 equiv) in DMSO (5 mL) was stirred at 100 ℃ for 4 h. After cooling to ambient temperature, EtOAc (20 mL) and H2O (20 mL) were added. The aqueous phase was extracted with EtOAc (20 mL x 2). The combined organic phases were washed with H ₂ O (50 mL x 2), dried with sodium sulfate, filtered, and concentrated to afford methyl (1S)-2-[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxopyri midin-2-yl]-1-(2- fluorophenyl)-3,4-dihydro-1H-isoquinoline-7-carboxylate (330 mg, 68%). ES MS M/Z = 541.20 [M+H] ⁺ . [00537] Step 8: A yellow solution of methyl (1S)-2-[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6- oxopyrimidin-2-yl]-1-(2-fluorophenyl)-3,4-dihydro-1H-isoquin oline-7-carboxylate (330 mg, 0.610 mmol, 1 equiv), LiBr (265 mg, 3.050 mmol, 5 equiv) in DMF (3 mL) was stirred at 100 ℃. After cooling to ambient temperature , EtOAc (20 mL) and H2O (20 mL) were added. The aqueous phase was extracted with EtOAc (20 mL x 2). The combined organic phases were washed with brine (60 mL x 2), dried with sodium sulfate, filtered, and concentrated. The residue was submitted to silica gel column giving methyl (1S)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyri midin-2-yl]-1-(2-fluorophenyl)-3,4- dihydro-1H-isoquinoline-7-carboxylate (300 mg, 84%). ES MS M/Z = 527.20 [M+H] ⁺ . [00538] Step 9: To a solution of methyl (1S)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6- oxopyrimidin-2-yl]-1-(2-fluorophenyl)-3,4-dihydro-1H-isoquin oline-7-carboxylate (300 mg, 0.570 mmol, 1 equiv) in THF (12 mL) and MeOH (4 mL), a solution of LiOH (41 mg, 1.710 mmol, 3 equiv) in H2O (4 mL) was added giving a white suspension, which stirred at ambient temperature for 2 h. After concentration, the residue was acidified to pH ~ 4 with HCl (2 M, aq.). The resulting mixture was extracted with ethyl acetate (50 mL X 3). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated to afford (1S)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl- 6-oxopyrimidin-2-yl]-1-(2-fluorophenyl)-3,4-dihydro-1H-isoqu inoline-7-carboxylic acid (250 mg) as a yellow solid.50 mg of the solid was submitted to Prep-HPLC with the following Column: Column: Xselect CSH C18 OBD Column, 30*150 mm, 5μm; Mobile Phase A: Water (0.1% FA), Mobile Phase B: acetonitrile; Flow rate: 60 mL/min mL/min; Gradient: 43% B to 73% B in 7min; Wave Length: 254nm/220nm nm; RT(min): 6.07 to provide (1S)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6- oxopyrimidin-2-yl]-1-(2-fluorophenyl)-3,4-dihydro-1H-isoquin oline-7-carboxylic acid (20.3 mg, 7%). ES MS M/Z =513.10 [M+H] ⁺ , UPLC: 99.502%; ¹ H NMR (300 MHz, DMSO-d6) δ 8.01 – 7.85 (m, 2 H), 7.83 – 7.65 (m, 1 H), 7.55 - 7.37 (m, 4 H), 7.30 – 6.98 (m, 4 H), 6.45 - 6.21 (m, 1 H), 3.68 – 3.55 (m, 4 H), 3.36 – 3.23 (m, 2 H), 3.12 – 2.98 (m, 1 H). [00539] The following compounds were synthesized in a similar manner: Example 104: (1R)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyri midin-2-yl]-1-(2- chlorophenyl)-3,4-dihydro-1H-isoquinoline-6-carboxylate [00540] ES MS M/Z = 543.1 [M+H] ⁺ , UPLC: 95%; ¹ H NMR (400 MHz, DMSO-d6) δ 10.59 (s, 1H), 7.83 – 7.92 (m, 3H), 7.74 (dd, J = 8.2, 1.8 Hz, 1H), 7.49 (dtd, J = 16.8, 7.4, 1.4 Hz, 2H), 7.35 – 7.42 (m, 1H), 7.27 (d, J = 4.5 Hz, 1H), 7.13 – 7.24 (m, 2H), 7.02 (d, J = 8.2 Hz, 1H), 6.48 (s, 1H), 3.85 (s, 3H), 3.62 (d, J = 13.0 Hz, 1H), 3.57 (s, 3H), 3.17 – 3.24 (d, J = 16.1 Hz, 1H), 3.01 (d, J = 16.1 Hz, 1H). Stereochemistry arbitrarily assigned. Example 105: (1R)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyri midin-2-yl]-1-(2- chlorophenyl)-3,4-dihydro-1H-isoquinoline-6-carboxylic acid [00541] ES MS M/Z = 529.2 [M+H] ⁺ ,UPLC: 95%; ¹ H NMR (300 MHz, DMSO-d6) δ 12.91 (s, 1H), 10.58 (s, 1H), 7.86 (d, J = 7.6 Hz, 1H), 7.86 (s, 2H), 7.71 (d, J = 7.5 Hz, 1H), 7.56 – 7.34 (m, 2H), 7.27 (d, J = 4.3 Hz, 1H), 7.23 – 7.14 (m, 3H), 6.99 (d, J = 8.3 Hz, 1H), 6.47 (s, 1H), 3.64 (s, 1H), 3.57 (s, 3H), 3.30 - 3.26 (m, 2H), 3.06 – 2.99 (m, 1H). Stereochemistry arbitrarily assigned. Example 106: (1S)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyri midin-2-yl]-1-(2- chlorophenyl)-3,4-dihydro-1H-isoquinoline-6-carboxylate [00542] ES MS M/Z = 543.1 [M+H] ⁺ , UPLC: 99%; ¹ H NMR (400 MHz, DMSO-d6) δ 10.59 (s, 1H), 7.92 - 7.83 (m, 3H), 7.74 (d, J = 8.2 Hz, 1H), 7.49 - 7.47 (m, 2H), 7.35 – 7.42 (m, 1H), 7.27 (d, J = 4.5 Hz, 1H), 7.24 - 7.13 (m, 2H), 7.02 (d, J = 8.2 Hz, 1H), 6.48 (s, 1H), 3.85 (s, 3H), 3.62 (d, J = 13.0 Hz, 1H), 3.57 (s, 3H), 3.24 - 3.17 (d, J = 16.1 Hz, 1H), 3.01 (d, J = 16.1 Hz, 1H). Stereochemistry arbitrarily assigned. Example 107: Methyl (R)-2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2-yl)-1-phenyl-1,2,3,4-tetrahydroisoquinoli ne-6-carboxylate [00543] ES MS M/Z = 509.2 [M+H] ⁺ , UPLC: 98%; ¹ H NMR (400 MHz, DMSO-d6) δ 10.28 (s, 1H), 7.95 -7.68 (m, 4H), 7.48 - 7.46 (m, 2H), 7.26 - 7.15 (m, 5H), 7.01 - 6.91 (m, 1H), 6.06 - 5.97(s, 1H), 3.84 (s, 3H), 3.55 (s, 4H), 3.34 - 3.23 (m, 1H), 3.08 - 3.03 (m, 1H), 2.07 (m, 1 H). Stereochemistry arbitrarily assigned. Example 108: (1S)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyri midin-2-yl]-1-(2- chlorophenyl)-3,4-dihydro-1H-isoquinoline-6-carboxylic acid [00544] ES MS M/Z = 529. [M+H] ⁺ , UPLC: 95%; ¹ H NMR (300 MHz, DMSO-d6) δ 12.91 (s, 1H), 10.58 (s, 1H), 7.86 (d, J = 7.6 Hz, 1H), 7.86 (s, 2H), 7.71 (d, J = 7.5 Hz, 1H), 7.56 – 7.34 (m, 2H), 7.27 (d, J = 4.3 Hz, 1H), 7.23 – 7.14 (m, 3H), 6.99 (d, J = 8.3 Hz, 1H), 6.47 (s, 1H), 3.64 (s, 1H), 3.57 (s, 3H), 3.30 - 3.26 (m, 2H), 3.06 – 2.99 (m, 1H). Stereochemistry arbitrarily assigned. Example 109: Methyl 2-[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxopyrimidin -2-yl]-1-(2- chlorophenyl)-3,4-dihydro-1H-isoquinoline-7-carboxylate [00545] ES MS M/Z = 529.2 [M+H] ⁺ , UPLC: 98%; ¹ H NMR (400 MHz, DMSO-d6) δ 12.89 (s, 1H), 10.15 (s, 1H), 7.98 - 7.86 (m, 2H), 7.78 (d, J = 8.1 Hz, 1H), 7.60 - 7.40 (m, 5H), 7.39 - 7.20 (m, 3H), 6.47 (s, 1H), 3.64 - 3.58 (m, 4H), 3.37 – 3.27 (m, 2H), 3.14 - 2.94 (m, 1H). Example 110: (1R)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyri midin-2-yl]-1-(2- chlorophenyl)-3,4-dihydro-1H-isoquinoline-7-carboxylic acid [00546] ES MS M/Z = 528.1 [M+H] ⁺ , UPLC: 99%; ¹ H NMR (400 MHz, DMSO-d6) δ 12.89 (s, 1H), 10.58 (s, 1H), 7.98 - 7.95 (m, 2H), 7.86 (d, J = 1.8 Hz, 1H),7.53 - 7.38 (m, 5H), 7.30 - 7.28 (m, 1H), 7.20 – 7.17 (m, 2H), 6.47 (s, 1H), 3.64 – 3.57 (m, 4H), 3.35 – 3.25 (m, 2H), 3.01 – 2.97(m, 1H). Stereochemistry arbitrarily assigned. Example 111: (1S)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyri midin-2-yl]-1-(2- chlorophenyl)-3,4-dihydro-1H-isoquinoline-7-carboxylic acid [00547] ES MS M/Z = 528.1 [M+H] ⁺ , UPLC: 99%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 12.89 (s, 1H), 10.58 (s, 1H), 7.86 (t, J = 7.5, 1.8 Hz, 2H), 7.78 (d, J = 8.0 Hz, 1H), 7.56 - 7.43 (m, 3H), 7.41 (d, J = 8.8 Hz, 2H), 7.29 (d, J = 6.0 Hz, 1H), 7.14 - 7.25 (m, 2H), 6.47 (s, 1H), 3.63 (d, J = 11.0 Hz, 1H), 3.58 (s, 3H), 3.23 - 3.36 (m, 2H), 3.00 (d, J = 17.0 Hz, 1H). Stereochemistry arbitrarily assigned. Example 112: 2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyrimidin -2-yl]-1-phenyl-3,4- dihydro-1H-isoquinoline-7-carboxylic acid [00548] ES MS M/Z = 495.1 [M+H] ⁺ , UPLC: 99%; ¹ H NMR (400 MHz, DMSO-d6) δ 10.56 (s, 1H), 7.92 – 7.90 (m, 2H), 7.79-7.73 (m, 1H), 7.60 (s, 2H), 7.50 (q, J = 7.8 Hz, 3H), 7.41 (d, J = 8.0 Hz, 1H), 7.30-7.19 (m, 4H), 7.15 (t, J = 7.0 Hz, 1H), 6.07 (s, 1H), 3.58 (s, 3H), 3.11-3.02 (m, 1H), 1.24 (s, 1H). Example 113: (1R)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyri midin-2-yl]-1-phenyl- 3,4-dihydro-1H-isoquinoline-7-carboxylic acid [00549] ES MS M/Z = 495.1 [M+H] ⁺ , UPLC: 92%; ¹ H NMR (300 MHz, DMSO-d6) δ 12.80 (s, 1H), 10.54 (s, 1H), 7.91 - 7.74 (m, 3H), 7.54 - 7.12 (m, 9H), 6.05 (s, 1H), 3.59 - 3.56 (m, 4H), 3.38 - 3.30 (m, 1H), 3.28 - 3.24 (m, 1H), 3.11 – 3.03 (m, 1H). Stereochemistry arbitrarily assigned. Example 114: (1S)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyri midin-2-yl]-1-phenyl- 3,4-dihydro-1H-isoquinoline-7-carboxylic acid [00550] ES MS M/Z = 495.2 [M+H] ⁺ , UPLC: 94%; ¹ H NMR (300 MHz, DMSO-d6) δ 12.81 (s, 1H), 10.55 (s, 1H), 7.93 - 7.72 (m, 3H), 7.55 - 7.40 (m, 4H), 7.25 - 7.05 (m, 5H), 6.07 (s, 1H), 3.62 - 3.50 (m, 4H), 3.63 - 3.45 (m, 1H), 3.21 - 3.00 (m, 2H). Stereochemistry arbitrarily assigned. [00551] Synthesis of 6-(1,3-benzoxazol-2-yl)-2-chloro-5-methoxy-3-methylpyrimidin -4-one: [00552] Step 1: A solution of methyl 2,6-dichloro-5-methoxypyrimidine-4-carboxylate (100 g, 422 mmol, 1 equiv) in H2O (800 mL) and THF (800 mL) was treated with lithium hydroxide (50.5 g, 2109 mmol, 5.00 equiv) in portions at ambient temperature. The resulting mixture was stirred for 12 h at 60 °C. The mixture was allowed to cool down to ambient temperature. The resulting mixture was concentrated under reduced pressure. The resulting mixture was washed with EA (3 x 300 mL). The mixture was acidified to pH 1 with conc. HCl. The resulting mixture was concentrated under vacuum to 200 mL. The precipitated solids were collected by filtration to afford 2-chloro-6-hydroxy-5- methoxypyrimidine-4-carboxylic acid (90 g, 99%) as a colorless solid. ES MS M/Z 204.95 [M+H] ⁺ . [00553] Step 2: To a stirred solution of 2-iodoaniline (50.6 g, 231.217 mmol, 1.1 equiv) and 2-chloro- 6-hydroxy-5-methoxypyrimidine-4-carboxylic acid (43 g, 210.197 mmol, 1.00 equiv) in DCM (1000 mL) was added T3P (334.4 g, 1050.985 mmol, 5.00 equiv) and DIEA (135.8 g, 1050.985 mmol, 5.00 equiv) in portions at ambient temperature. The resulting mixture was stirred for 24 h at ambient temperature. The resulting mixture was diluted with water (1000 mL). The resulting mixture was extracted with DCM (3 x 200 mL). The combined organic layers were washed with brine (3 x 300 mL), dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by trituration with ethyl acetate (1000 mL) to afford 2-chloro-N-(2- iodophenyl)-5-methoxy-6-oxo-1H-pyrimidine-4-carboxamide (70 g, 82%) as a colorless solid. ES MS M/Z 405.90 [M+H] ⁺ . [00554] Step 3: A mixture of 1,10-phenanthroline (8.0 g, 44.381 mmol, 0.2 equiv) and CuCN (3.97 g, 44.381 mmol, 0.2 equiv) in DMF (1000 mL) was stirred for 30 min at ambient temperature under nitrogen atmosphere. To the above mixture was added 2-chloro-N-(2-iodophenyl)-5-methoxy-6-oxo-1H- pyrimidine-4-carboxamide (90 g, 221.904 mmol) and Cs2CO3 (217 g, 665.712 mmol) in portions at ambient temperature. The resulting mixture was stirred for additional 16 h at 100 °C. The crude product was used directly without purification. ES MS M/Z 278.10 [M+H] ⁺ . [00555] Step 4: To the mixture of step 3 was added CH ₃ I (63 g, 443.808 mmol, 2 equiv) dropwise over 10 min at ambient temperature. The resulting mixture was stirred for additional 12 h at ambient temperature. The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE/EA (2:1) to afford 6-(1,3-benzoxazol-2-yl)-2-chloro-5- methoxy-3-methylpyrimidin-4-one (40 g, 62%). ES MS M/Z 292.05 [M+H] ⁺ . Example 115: 2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyrimidin -2-yl]-3-phenyl-1,3- dihydroisoindole-5-carboxylic acid

[00556] Step 1: A solution of 6-bromo-2,3-dihydroisoindol-1-one (15 g, 70.74 mmol, 1 equiv) and Boc ₂ O (18.5 g, 84.9 mmol) in THF (200 mL) was treated with DMAP (0.86 g, 7.07 mmol, 0.1 equiv) ^{followed by the addition of Et} 3 ^{N (17.90 g, 176.85 mmol, 2.5 equiv) dropwise at ambient temperature.} The resulting mixture was stirred overnight at 65 °C. The mixture was allowed to cool down to ambient temperature. The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (10:1) to afford tert-butyl 6-bromo-1-oxo-3H- isoindole-2-carboxylate (18 g, 81.51%) as a colorless solid. ES MS M/Z 212.05 [M-Boc+H] ⁺ . [00557] Step 2: To a stirred solution/mixture of tert-butyl 6-bromo-1-oxo-3H-isoindole-2-carboxylate (14 g, 44.9 mmol, 1 equiv) in THF (150 mL) was added phenyllithium (28.3 mL 1.9 M in hexane, 53.8 mmol) dropwise at -78 °C under nitrogen atmosphere. The resulting mixture was stirred for 1 h at -78 °C under nitrogen atmosphere. Then the resulting mixture was stirred for 30 min at ambient temperature under a nitrogen atmosphere. The reaction was quenched with sat. NH4Cl (aq.) at 0 °C. The resulting mixture was extracted with EA (3 x 300 mL). The combined organic layers were washed with brine (2 x 100 mL) then dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE/EA (5:1) to afford tert-butyl N-[(2-benzoyl-4-bromophenyl)methyl]carbamate (12 g, 69%) as a colorless solid. ES MS M/Z 290.15 [M-Boc+H] ⁺ . [00558] Step 3: To a stirred solution/mixture of tert-butyl N-[(2-benzoyl-4- bromophenyl)methyl]carbamate (10 g, 25.623 mmol, 1 equiv) in MeOH (200 mL) was added NaBH ₄ (2.9 g, 76.869 mmol, 3 equiv) in portions at 0 °C under. The resulting mixture was stirred for 1 h at ambient temperature. The mixture was allowed to cool down to 0 °C. The reaction was quenched by the addition of sat. NH4Cl (aq.) (100 mL) at 0 °C. The resulting mixture was concentrated under reduced pressure. The residue was dissolved in water (100 mL). The resulting mixture was extracted with EA (3 x 100 mL). The combined organic layers were washed with brine (3x30 mL), dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure to afford tert-butyl N-({4- bromo-2-[hydroxy(phenyl)methyl]phenyl}methyl)carbamate (9 g, 89.54%) as a colorless solid. The crude product was used in the next step directly without further purification. ES MS M/Z = 390.00 [M- H]-. [00559] Step 4: To a stirred solution of tert-butyl N-({4-bromo-2- [hydroxy(phenyl)methyl]phenyl}methyl)-carbamate (7 g, 17.844 mmol) in DCM (500 mL) was added TFAA (4 mL) dropwise at 0 °C. The resulting mixture was stirred for 30 min at ambient temperature. The reaction was quenched by the addition of NaHCO3(300 mL) at ambient temperature. The resulting mixture was extracted with DCM (3 x 100 mL). The combined organic layers were washed with brine (1 x 100 mL), dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The crude product mixture was used in the next step directly without further purification. ES MS M/Z 274.05 [M-Boc+H] ⁺ . [00560] Step 5: To a 500 mL pressure tank reactor was added tert-butyl 6-bromo-1-phenyl-1,3- dihydroisoindole-2-carboxylate (6 g, 16.031 mmol) in MeOH (300 mL), TEA (8.11 g, 80.155 mmol) and Pd(dppf)Cl2 (1.74 g, 2.405 mmol) were added, and the reaction mixture was stirred under CO (30 atm) for 16 h at 130 ℃. After addition, the mixture was concentrated and quenched with NH4Cl (aq.100 mL) and extracted with EA (3 x 300 mL). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated to provide 2-tert-butyl 5-methyl 3-phenyl-1,3- dihydroisoindole-2,5-dicarboxylate as a brown oil (4.5 g, 79% yield). ES MS M/Z 254.15 [M-Boc+H] ⁺ . [00561] Step 6: To a stirred solution of 2-tert-butyl 5-methyl 3-phenyl-1,3-dihydroisoindole-2,5- dicarboxylate (3 g, 8.489 mmol, 1 equiv) in 4M HCl in dioxane (20 mL). The resulting mixture was stirred for 2 h at ambient temperature. The resulting mixture was concentrated under reduced pressure. The residue was purified by trituration with diethyl ether (50 mL) to afford methyl 3-phenyl-2,3-dihydro- 1H-isoindole-5-carboxylate (2 g, 93%) as a colorless solid. ES MS M/Z 254.10 [M+H] ⁺ . [00562] Step 7: A mixture of ethyl 3-(3-phenylmorpholin-2-yl)propanoate (1 g, 3.797 mmol, 1 equiv) ,6-(1,3-benzoxazol-2-yl)-2-chloro-5-methoxy-3-methylpyrimidi n-4-one (1.33 g, 4.556 mmol, 1.2 equiv) and cesium fluoride (0.69 g, 4.56 mmol, 1.2 equiv) in DMSO (10 mL) was stirred for 16 h at 80 °C. The mixture was allowed to cool down to ambient temperature, the resulting mixture was diluted with water (50 mL). The precipitated solids were collected by filtration and washed with Et2O (3 x 20 mL) to afford ethyl 3-{4-[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxopyrimi din-2-yl]-3-phenylmorpholin-2- yl}propanoate (1.2 g, 77%) as colorless solid. ES MS M/Z = 519.25 [M+H] ⁺ . [00563] Step 8: A solution of methyl 2-[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxopyrimidin - 2-yl]-3-phenyl-1,3-dihydroisoindole-5-carboxylate (150 mg, 0.295 mmol), LiBr (256 mg, 2.950 mmol) in DMF (3 mL) was stirred overnight at 80 °C. The resulting mixture was diluted with water (30 mL). The precipitated solids were collected by filtration and washed with water (3 x 20 mL). The residue was purified by trituration with diethyl ether (30 mL). The precipitated solids were collected by filtration and washed with diethyl ether (3 x 30 mL) to afford methyl 2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl- 6-oxopyrimidin-2-yl]-3-phenyl-1,3-dihydroisoindole-5-carboxy late (120 mg, 82%) as a colorless solid. [00564] Step 9: A solution/mixture of methyl 2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6- oxopyrimidin-2-yl]-3-phenyl-1,3-dihydroisoindole-5-carboxyla te (150 mg, 0.303 mmol) and LiOH (22 mg, 0.909 mmol) in THF (5 mL) and H2O (5 mL) was stirred for overnight at ambient temperature. The resulting mixture was diluted with water (20 mL). The resulting mixture was washed with 3 x 30 mL of DCM. The water layer was acidified to pH = 2 with HCl (aq.2.0 M). The precipitated solids were collected by filtration and washed with DCM (2 x 20 mL), The solid was submitted to Prep-HPLC with following conditions: Column: Xselect CSH C18 OBD Column, 30*150 mm, 5 μm; Mobile Phase A: Water(0.1% FA), Mobile Phase B: acetonitrile; Flow rate: 60 mL/min; Gradient: 45% B to 75% B in 7 min; Wave Length: 254 nm/220 nm; Rt1 (min): 6.1 to afforded 2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1- methyl-6-oxopyrimidin-2-yl]-3-phenyl-1,3-dihydroisoindole-5- carboxylic (3.5 mg, 2% yield). ES MS M/Z = 481.15 [M+H] ⁺ , UPLC: 98%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 7.91 - 7.89 (m, 4H), 7.69 - 7.40 (m, 8H), 7.33 (t, J = 7.4 Hz, 3H), 7.24 (t, J = 7.2 Hz, 1H), 6.81 (s, 1H), 5.49 (d, J = 14.7 Hz, 1H), 4.77 (d, J = 14.8 Hz, 1H), 3.60 (s, 3H), 1.24 (s, 2H). Example 116 and 117: (1R)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyri midin-2-yl]-1- phenyl-3,4-dihydro-1H-isoquinoline-6-carboxylic acid and (1S)-2-[4-(1,3-benzoxazol-2-yl)-5- hydroxy-1-methyl-6-oxopyrimidin-2-yl]-1-phenyl-3,4-dihydro-1 H-isoquinoline-6-carboxylic acid [00565] To a stirred solution of methyl (1S)-2-[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6- oxopyrimidin-2-yl]-1-phenyl-3,4-dihydro-1H-isoquinoline-6-ca rboxylate (1.6 g, 3.06 mmol, 1 equiv) in THF (4 mL), H2O (1 mL) and MeOH (1 mL) was added LiOH (0.44 g, 18.372 mmol, 6 equiv) in portions at ambient temperature under air atmosphere. The resulting mixture was stirred overnight at ambient temperature then concentrated under reduced pressure. The resulting mixture was diluted with water (20 mL). The mixture was acidified to pH 4 with HCl (1M). The precipitated solids were collected by filtration and washed with water (2 x 30 mL). This resulted in (1S)-2-[4-(1,3-benzoxazol-2-yl)-5- methoxy-1-methyl-6-oxopyrimidin-2-yl]-1-phenyl-3,4-dihydro-1 H-isoquinoline-6-carboxylic acid (1.3 g, 84%) as an off-white solid. ES MS M/Z = 509.10 [M+H] ⁺ . [00566] A solution of (1S)-2-[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxopyri midin-2-yl]-1- phenyl-3,4-dihydro-1H-isoquinoline-6-carboxylic acid (1.3 g, 2.556 mmol, 1 equiv) in DCM (10 mL) was added BBr ₃ (5.11 mL, 5.112 mmol, 2 equiv) dropwise at -20 °C under nitrogen atmosphere. The resulting mixture was stirred for 1 h at -20 °C under nitrogen atmosphere. The reaction was monitored by LCMS. The reaction was quenched with water at ambient temperature. The resulting mixture was concentrated under reduced pressure to afford 2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6- oxopyrimidin-2-yl]-1-phenyl-3,4-dihydro-1H-isoquinoline-6-ca rboxylic acid (650 mg, 46%) as a colorless solid. ES MS M/Z = 495.10 [M+H] ⁺ . [00567] The solid was purified by Prep-SFC (Column: CHIRALPAK IG 3*25 cm, 5 μm; Mobile Phase A: CO2, Mobile Phase B: MeOH: acetonitrile=1: 1; Flow rate: 100 mL/min; Gradient: isocratic 50% B; Column Temperature(℃): 35; Back Pressure(bar): 100; Wave Length: 220 nm; RT(min): 3.87; RT2(min): 5.45; Sample Solvent: MEOH; Injection Volume: 1.5 mL) to afford (1R)-2-[4-(1,3- benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyrimidin-2-yl]-1-p henyl-3,4-dihydro-1H-isoquinoline-6- carboxylic acid (20.7 mg, 21%) as an off-white solid. ES MS M/Z = 495.15 [M+H] ⁺ ; ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 12.79 (s, 1H), 10.59 (s, 1H), 7.92 – 7.86 (m, 3H), 7.68 – 7.65 (m, 1H), 7.52 – 7.46 (m, 2H), 7.29 – 7.13 (m, 5H), 6.98 (d, J = 8.2 Hz, 1H), 6.07 (s, 1H), 3.56 (s, 4H), 3.31 – 3.15 (m, 1H), 3.05 – 2.29 (m, 1H) and (1S)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyri midin-2-yl]-1- phenyl-3,4-dihydro-1H-isoquinoline-6-carboxylic acid (22.8 mg, 15.18%) . ES MS M/Z = 495.1 [M+H] ⁺ , UPLC: 99%; ¹ H NMR (400 MHz, DMSO-d6) δ 12.76 (s, 1H), 10.59 (s, 1H), 7.87 – 7.96 (m, 3H), 7.68 (d, J = 7.6 Hz, 1H), 7.48 – 7.54 (m, 2H), 7.14 – 7.29 (m, 5H), 6.98 (d, J = 8.4 Hz, 1H), 6.07 (s, 1H), 3.57 (s, 4H), 3.24 – 3.27 (m, 2H), 3.05 (d, J = 15.2 Hz, 1H). Example 119: 4-({[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyrimid in-2- yl](methyl)amino}(phenyl)methyl)-N-methylbenzamide [00568] Step 1: To a stirred mixture of 6-(1,3-benzoxazol-2-yl)-2-chloro-5-methoxy-3- methylpyrimidin-4-one (1 g, 3.43 mmol, 1 equiv) and 1-(4-bromophenyl)-1-phenylmethanamine (899 mg, 3.43 mmol, 1 equiv) in EtOH (10 mL) were added DIEA (1.3 g, 10.28 mmol, 3 equiv). The reaction was stirred at 80 °C for 12 h. The resulting mixture was concentrated under vacuum. The residue was purified by trituration with EtOH (10 mL). The precipitated solids were collected by filtration and washed with EtOH (3x4 mL) to afford 6-(1,3-benzoxazol-2-yl)-2-{[(4- bromophenyl)(phenyl)methyl]amino}-5-methoxy-3-methylpyrimidi n-4-one (700 mg, 35.52%) as an off- white solid. ES MS M/Z 517.0 [M+H] ⁺ . [00569] Step 2: To a stirred mixture of 6-(1,3-benzoxazol-2-yl)-2-{[(4- bromophenyl)(phenyl)methyl]amino}-5-methoxy-3-methylpyrimidi n-4-one (700 mg, 1.353 mmol, 1 equiv) in DMF (7 mL) was added MeI (384 mg, 2.71 mmol, 2 equiv) and Cs2CO3 (1.1 g, 3.38 mmol, 2.5 equiv). The reaction was stirred at ambient temperature for 2 h. The residue was purified by trituration with water (5 mL). The precipitated solids were collected by filtration and washed with water (3 x 3 mL) to afford 6-(1,3-benzoxazol-2-yl)-2-{[(4-bromophenyl)(phenyl)methyl](m ethyl)amino}-5-methoxy-3- methylpyrimidin-4-one (700 mg, 88%) as a colorless solid. ES MS M/Z 531.0 [M+H] ⁺ . [00570] Step 3: To a stirred mixture of 6-(1,3-benzoxazol-2-yl)-2-{[(4- bromophenyl)(phenyl)methyl](methyl)amino}-5-methoxy-3-methyl pyrimidin-4-one (200 mg, 0.376 mmol, 1 equiv) and lithium(1+) formate (59 mg, 1.13 mmol, 3 equiv) in DMF (15 mL) was added Ac ₂ O (76.8 mg, 0.752 mmol, 2 equiv) and Pd(OAc)2 (2.11 mg, 0.009 mmol, 0.025 equiv), DPPF (5.20 mg, 0.009 mmol, 0.025 equiv), and DIEA (97.29 mg, 0.752 mmol, 2 equiv). The reaction was stirred at 120 °C under nitrogen for 2.5 h.50% The resulting mixture was added water (20 ml) and extracted with EtOAc (3 x 20 mL). The combined organic layers were washed with brine (15 mL), dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography to afford 4-({[4-(1,3-benzoxazol-2-yl)-5-methoxy-1- methyl-6-oxopyrimidin-2-yl](methyl)amino}(phenyl)methyl)benz oic acid (150 mg, 64.22%) as a yellow oil. ES MS M/Z 497.2 [M+H] ⁺ . [00571] Step 4: To a stirred mixture of 4-({[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6- oxopyrimidin-2-yl](methyl)amino}(phenyl)methyl)benzoic acid (150 mg, 0.302 mmol, 1 equiv) and methylamine hydrochloride (24 mg, 0.362 mmol, 1.2 equiv) in DMF (1.5 mL) was added HATU (229 mg, 0.604 mmol, 2 equiv) and DIEA (117 mg, 0.906 mmol, 3 equiv). The reaction was stirred at ambient temperature for 2 h. The residue was purified by reversed-phase flash chromatography to afford 4-({[4- (1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxopyrimidin-2-yl ](methyl)amino}(phenyl)methyl)-N- methylbenzamide (130 mg, 76%) as a yellow solid. ES MS M/Z 510.2 [M+H] ⁺ . [00572] Step 5: To a stirred mixture of 4-({[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6- oxopyrimidin-2-yl](methyl)amino}(phenyl)methyl)-N-methylbenz amide (50 mg, 0.098 mmol, 1 equiv) in DMF (1 mL) was added dodecane-1-thiol (39 mg, 0.196 mmol, 2 equiv) and NaOMe (11 mg, 0.196 mmol, 2 equiv). The reaction was stirred at 110 °C for 12 h under nitrogen atmosphere. The crude product was purified by Prep-HPLC (Column: XSelect CSH C18, 19*250 mm, 5μm; Mobile Phase A: Water(0.1% FA), Mobile Phase B: acetonitrile; Flow rate: 25 mL/min mL/min; Gradient: 41% B to 71% B in7min; Wave Length: 254nm nm; RT (min): 6.78) to afford 4-({[4-(1,3-benzoxazol-2-yl)-5-hydroxy- 1-methyl-6-oxopyrimidin-2-yl](methyl)amino}(phenyl)methyl)-N -methylbenzamide (6.0 mg, 12%). ES MS M/Z 496.1 [M+H] ⁺ , UPLC 99%; ¹ H NMR (400 MHz, DMSO-d6) δ 10.59 (s, 1H), 8.33 (d, J = 4.5 Hz, 1H), 7.82 – 7.91 (m, 2H), 7.68 – 7.74 (m, 2H), 7.42 – 7.58 (m, 6H), 7.30 (t, J = 7.6 Hz, 2H), 7.15 – 7.24 (m, 1H), 5.79 (s, 1H), 3.69 (s, 3H), 2.71 (d, J = 4.5 Hz, 3H), 2.58 (s, 3H). Example 120: 6-({[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxopyrimid in-2- yl](methyl)amino}(phenyl) methyl)-2-methyl-3H-isoindol-1-one [00573] Step 1: To the mixture of 3-oxo-1,2-dihydroisoindole-5-carbaldehyde (1 g, 6.205 mmol, 1 equiv) in THF (20 mL) was added titanium (IV) ethoxide (4.25 g, 18.62 mmol, 3 equiv) and tert- butanesulfinamide (0.75 g, 6.21 mmol, 1 equiv). The mixture was stirred at ambient temperature for 4 h. The mixture was diluted with brine (20 mL) and filtered. The filtrate was diluted with H2O (30 mL) and extracted by EtOAc (30 mL x 3). The organic layer was combined, washed with brine (100 mL), dried over sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography, eluted with DCM / MeOH (10:1) to afford 2-methyl-N-[(1E)-(3-oxo-1,2- dihydroisoindol-5-yl)methylidene]propane-2-sulfinamide (800 mg, 49%) as a yellow oil. ES MS M/Z = 265.1 [M+H] ⁺ . [00574] Step 2: To the mixture of 2-methyl-N-[(1E)-(3-oxo-1,2-dihydroisoindol-5- yl)methylidene]propane-2-sulfinamide (800 mg, 3.03 mmol, 1 equiv) in THF (20 mL) was added PhLi (1.99 mL, 3.78 mmol, 2 equiv) at -78°C under nitrogen atmosphere. The mixture was stirred for 2 h then warmed to ambient temperature and stirred for an additional 2 h. The mixture was quenched with sat. aq. NH4Cl (30mL) and extracted with EtOAc (20 mL x 3). The organic layer was combined, washed by brine (50 mL), dried over sodium sulfate, filtered, and concentrated. The residue was purified by reversed- phase flash chromatography (column, C18 silica gel; mobile phase, acetonitrile in Water (0.05% TFA), 10% to 50% gradient in 30 min; detector, UV 254 nm) to afford 2-methyl-N-[(3-oxo-1,2- dihydroisoindol-5-yl)(phenyl)methyl]propane-2-sulfinamide (400 mg, 39%) as a light yellow solid. ES MS M/Z = 365.1 [M+Na] ⁺ . [00575] Step 3: A mixture of 2-methyl-N-[(3-oxo-1,2-dihydroisoindol-5-yl)(phenyl)methyl]p ropane-2- sulfinamide (140 mg, 0.409 mmol, 1 equiv) 1,4-dioxane (3 mL) with HCl (gas) was stirred at ambient temperature for 1 h. The mixture was concentrated under reduced pressure to afford 6- [amino(phenyl)methyl]-2,3-dihydroisoindol-1-one (80 mg, 82%) as a yellow solid. ¹ H NMR (300 MHz, DMSO-d6) δ 9.11 (s, 3H), 8.67 (s, 1H), 7.85 (s, 1H), 7.74 – 7.66 (m, 1H), 7.63 (d, J = 7.9 Hz, 1H), 7.56 – 7.33 (m, 4H), 5.82 (d, J = 5.7 Hz, 1H), 4.38 (s, 2H). [00576] Step 4: To the mixture of 6-[amino(phenyl)methyl]-2,3-dihydroisoindol-1-one (60 mg, 0.252 mmol, 1 equiv) and 6-(1,3-benzoxazol-2-yl)-2-chloro-5-methoxy-3-methylpyrimidin -4-one (73 mg, 0.252 mmol, 1 equiv) in DMSO (2 mL) was added DIEA (48 mg, 0.378 mmol, 1.5 equiv). The mixture was stirred at 120 °C for 1 h. The residue was purified by reversed-phase flash chromatography to afford 6-({[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxopyrimid in-2-yl]amino}(phenyl)methyl)-2,3- dihydroisoindol-1-one (40 mg, 32%) as a yellow solid. ES MS M/Z = 494.2 [M+H] ⁺ . [00577] Step 5: To the mixture of 6-({[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxopyrimid in- 2-yl]amino}(phenyl)methyl)-2,3-dihydroisoindol-1-one (30 mg, 0.061 mmol, 1 equiv) in DMF (2 mL) was added CH ₃ I (26 mg, 0.183 mmol, 3 equiv) and Cs ₂ CO ₃ (39 mg, 0.122 mmol, 2 equiv). The mixture was stirred at ambient temperature for 2 h then filtered. The filtrate was purified by prep-HPLC (Column: Xselect CSH C18 OBD 30*150mm; Mobile Phase A: Water (0.1% FA), Mobile Phase B: acetonitrile; Flow rate: 60 mL/min mL/min; Gradient: 17% B to 42% B in 9 min; Wave Length: 254nm/220nm; RT(min): 8.9) to afford 6-({[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxopyrimid in-2- yl](methyl)amino}(phenyl)methyl)-2-methyl-3H-isoindol-1-one (2.8 mg, 9%). ES MS M/Z =522.2 [M+H] ⁺ , UPLC: 97%; ¹ H NMR (400 MHz, DMSO-d6) δ 7.91 – 7.81 (m, 2H), 7.71 – 7.61 (m, 2H), 7.55 – 7.24 (m, 8H), 6.03 (s, 1H), 4.39 (s, 2H), 3.89 (s, 3H), 3.61 (s, 3H), 3.03 (s, 3H), 2.64 (s, 3H) and 6-({[4- (1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxopyrimidin-2-yl ](methyl)amino}(phenyl)methyl)-2,3- dihydroisoindol-1-one (40 mg, 19%) as a yellow solid. ES MS M/Z = 508.2 [M+H] ⁺ . Example 121: 6-({[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyrimid in-2- yl](methyl)amino}(phenyl)methyl)-2,3-dihydroisoindol-1-one [00578] To the mixture of 6-({[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxopyrimid in-2- yl](methyl)amino}(phenyl)methyl)-2,3-dihydroisoindol-1-one (50 mg, 0.10 mmol, 1 equiv) in DMF (2 mL) was added LiCl (63 mg). The mixture was stirred at 100 °C for 16 h. The mixture was purified by prep-HPLC (Column: XSelect CSH C18 Column, 19*250 mm, 5μm; Mobile Phase A: Water(0.1% FA), Mobile Phase B: acetonitrile; Flow rate: 25 mL/min mL/min; Gradient: 38% B to 68% B in7min; Wave Length: 254nm nm; RT(min): 6.58) to afford 6-({[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6- oxopyrimidin-2-yl](methyl)amino}(phenyl)methyl)-2,3-dihydroi soindol-1-one (1.9 mg, 3.50%) as an off- white solid. ES MS M/Z = 494.2 [M+H] ⁺ , UPLC: 89%; ¹ H NMR (300 MHz, DMSO-d6) δ 10.55 (br, 1H), 8.52 (s, 1H), 7.93 – 7.81 (m, 2H), 7.79 – 7.66 (m, 2H), 7.65 - 7.57 (m 1H), 7.54 - 7.44(m, 1H), 7.43 - 7.36 (m, 1H), 7.35 - 7.28(m, 3H), 7.25 - 7.20 (m, 1H), 5.89 (s, 1H), 4.28 (s, 2H), 3.68 (s, 3H), 2.61 (s, 3H). Example 122: [4-({[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyrimi din-2- yl](methyl)amino}(phenyl)methyl)phenyl]acetic acid [00579] Step 1: To a stirred mixture of 6-(1,3-benzoxazol-2-yl)-2-{[(4- bromophenyl)(phenyl)methyl](methyl)amino}-5-methoxy-3-methyl pyrimidin-4-one (200 mg, 0.376 mmol, 1 equiv) in DMF (2 mL) was added tert-butyl[(1-methoxyethenyl)oxy]dimethylsilane (567 mg, 3.01 mmol, 8 equiv) and LiF (20 mg, 0.752 mmol, 2 equiv) and Pd(t-Bu3P)2 (19 mg, 0.038 mmol, 0.1 equiv). The reaction was stirred at 90 C under a nitrogen atmosphere for 1 h. The resulting mixture was diluted with water (15 mL) and extracted with EtOAc (3 x 15 mL). The combined organic layers were washed with brine (8 mL) and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by Prep-TLC (PE/EA=1:1) to afford methyl 2-[4-({[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxopyri midin-2- yl](methyl)amino}(phenyl)methyl)phenyl]acetate (210 mg, 96%) as a light yellow oil. ES MS M/Z = 525.35 [M+H] ⁺ . [00580] Step 2: To a stirred mixture of methyl 2-[4-({[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6- oxopyrimidin-2-yl](methyl)amino}(phenyl)methyl)phenyl]acetat e (160 mg, 0.305 mmol, 1 equiv) in DMF (2 mL) was added 1-dodecanethiol (185 mg, 0.915 mmol, 3 equiv) and NaOMe (49 mg, 0.915 mmol, 3 equiv). The reaction was stirred at 110 C under nitrogen atmosphere for 2 h. The residue was purified by reversed-phase flash chromatography to afford methyl 2-[4-({[4-(1,3-benzoxazol-2-yl)-5- hydroxy-1-methyl-6-oxopyrimidin-2-yl](methyl)amino}(phenyl)m ethyl)phenyl]acetate (70 mg, 40%) as a yellow solid. ES MS M/Z = 511.20 [M+H] ⁺ . [00581] Step 3: To a stirred mixture of methyl 2-[4-({[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6- oxopyrimidin-2-yl](methyl)amino}(phenyl)methyl)phenyl]acetat e (40 mg, 0.078 mmol, 1 equiv) in DCE (1 mL) were added trimethylstannanol (113 mg, 0.624 mmol, 8 equiv). The reaction was stirred at 80 C for 12 h. The resulting mixture was concentrated under vacuum. The residue was dissolved in DMF (1 mL). The crude product was purified by Prep-HPLC (Column: XSelect CSH C ₁₈ Column, 19*250 mm, 5μm; Mobile Phase A: Water (0.1% FA), Mobile Phase B: acetonitrile; Flow rate: 25 mL/min mL/min; Gradient: 47% B to 77% B in7min; Wavelength: 254nm nm; RT(min): 6.89). The fractions were combined and lyophilized to afford [4-({[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyrimi din- 2-yl](methyl)amino}(phenyl)methyl)phenyl]acetic acid (1.2 mg, 3%). ES MS M/Z = 497.15 [M+H] ⁺ ,UPLC: 97%; ¹ H NMR (300 MHz, DMSO-d6) δ 12.24 (s, 1H), 10.56 (s, 1H), 7.82-7.93 (m, 2H), 7.37-7.56 (m, 6H), 7.28 (t, J = 7.5 Hz, 2H), 7.11-7.22 (m, 3H), 5.74 (s, 1H), 3.67 (s, 3H), 3.50 (s, 2H), 2.58 (s, 3H). Example 123 and 124: (S)-6-(benzo[d]oxazol-2-yl)-2-((bicyclo[1.1.1]pentan-1- yl(phenyl)methyl)(methyl)amino)-5-hydroxy-3-methylpyrimidin- 4(3H)-one and (R)-6- (benzo[d]oxazol-2-yl)-2-((bicyclo[1.1.1]pentan-1-yl(phenyl)m ethyl)(methyl)amino)-5-hydroxy-3- methylpyrimidin-4(3H)-one [00582] To a stirred mixture of benzophenone (5 g, 27.439 mmol, 1 equiv) in DCM (50 mL) was added benzylamine (2.94 g, 27.439 mmol, 1 equiv) dropwise at ambient temperature under air atmosphere. The resulting mixture was stirred for additional overnight at ambient temperature. The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (5:1) to afford benzyl(diphenylmethylidene)amine (5 g, 67.15%) as a light yellow oil. ES MS M/Z = 272.2 [M+H] ⁺ . [00583] A solution of benzyl(diphenylmethylidene)amine (5.5 g, 20.268 mmol, 1 equiv) in THF (50 mL) was treated with tricyclo[1.1.1.0^{1,3}]pentane (1.61 g, 24.322 mmol, 1.2 equiv) for 30 min at - 78 C under nitrogen atmosphere followed by the addition of LDA (2.61 g, 24.322 mmol, 1.2 equiv) dropwise at -78 C. The mixture was added with sat. aq. NH4Cl (100 mL) and extracted by EtOAc (80 mL x 3). The organic layer was combined, washed by brine, dried over sodium sulfate, filtered, and concentrated. The crude product was used in the next step directly without further purification. ES MS M/Z = 338.1 [M+H] ⁺ . [00584] A solution of {bicyclo[1.1.1]pentan-1-yl(phenyl)methyl}(diphenylmethyliden e)amine (5.5 g, 16.3 mmol, 1 equiv) in THF (100 mL) was treated with hydrogen chloride (5 mL) for 30 min at ambient temperature. The mixture was diluted by DCM (50 mL) and washed by water (100 mL). The water layer was concentrated under vacuum to afford 1-{bicyclo[1.1.1]pentan-1-yl}-1-phenylmethanamine hydrochloride (2.6 g, 77%) as colorless solid. ES MS M/Z = 174.2 [M+H] ⁺ . [00585] To a stirred mixture of 6-(1,3-benzoxazol-2-yl)-2-chloro-5-methoxy-3-methylpyrimidin -4-one (200 mg, 0.686 mmol, 1 equiv) and 1-{bicyclo[1.1.1]pentan-1-yl}-1-phenylmethanamine (118 mg, 0.686 mmol, 1 equiv) in EtOH (2 mL) were added DIEA (266 mg, 2.058 mmol, 3 equiv). The reaction was stirred at 80 C for 12 h. The resulting mixture was concentrated under vacuum. The residue was dissolved in DMF (2 mL). The residue was purified by reversed-phase flash chromatography with the following conditions to afford 6-(1,3-benzoxazol-2-yl)-2-({bicyclo[1.1.1]pentan-1- yl(phenyl)methyl}amino)-5-methoxy-3-methylpyrimidin-4-one (120 mg, 37%) as a light yellow oil. ES MS M/Z = 429.3 [M+H] ⁺ . [00586] To a stirred mixture of 6-(1,3-benzoxazol-2-yl)-2-{[(4-bromophenyl)(phenyl)methyl]am ino}- 5-methoxy-3-methylpyrimidin-4-one (110 mg, 0.213 mmol, 1 equiv) in DMF (1 mL) were added MeI (60 mg, 0.426 mmol, 2 equiv) and Cs ₂ CO ₃ (173 mg, 0.532 mmol, 2.5 equiv). The reaction was stirred at ambient temperature for 2 h. The resulting mixture was filtered, the filter cake was washed with DMF (1x1 mL). The filtrate was used in the next step directly without further purification. ES MS M/Z = 443.3 [M+H] ⁺ . [00587] To a stirred mixture of 6-(1,3-benzoxazol-2-yl)-2-({bicyclo[1.1.1]pentan-1- yl(phenyl)methyl}(methyl)amino)-5-methoxy-3-methylpyrimidin- 4-one (90 mg, 0.20 mmol, 1 equiv) in DMF (1 mL, 12.92 mmol, 63.5 equiv) was added LiBr (176 mg, 2.03 mmol, 10 equiv). The reaction was stirred at 80 C for 16 h. The mixture was purified by reversed-phase flash chromatography to afford 6- (1,3-benzoxazol-2-yl)-2-({bicyclo[1.1.1]pentan-1-yl(phenyl)m ethyl}(methyl)amino)-5-hydroxy-3- methylpyrimidin-4-one (15.4 mg, 18%) (50 mg). ES MS M/Z = 429.1 [M+H] ⁺ . [00588] The racemates of 6-(1,3-benzoxazol-2-yl)-2-({bicyclo[1.1.1]pentan-1- yl(phenyl)methyl}(methyl)amino)-5-hydroxy-3-methylpyrimidin- 4-one (15.4 mg, 17.6%) was separated Prep-chiral-HPLC (Column: CHIRALPAKIG-34.6*50mm*3um; Mobile Phase A: MTBE (0.1%DEA): IPA=70:30; Flow rate: 1.0mL/min mL/min; Gradient: isocratic) to afford two compounds: 6-(1,3- benzoxazol-2-yl)-2-({bicyclo[1.1.1]pentan-1-yl(phenyl)methyl }(methyl)amino)-5-hydroxy-3- methylpyrimidin-4-one (13.7 mg, 15.71%) as a colorless solid. ES MS M/Z = 429.1 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.68 (s, 1H), 7.96-7.87 (m, 2H), 7.53-7.43 (m, 2H), 7.42-7.33 (m, 4H), 7.32- 7.24 (m, 1H), 4.62 (s, 1H), 3.65 (s, 3H), 2.54 (s, 3H), 2.35 (s, 1H), 1.63-1.49 (m, 6H) and 6-(1,3- benzoxazol-2-yl)-2-({bicyclo[1.1.1]pentan-1-yl(phenyl)methyl }(methyl)amino)-5-hydroxy-3- methylpyrimidin-4-one. ES MS M/Z = 429.1 [M+H] ⁺ ,UPLC: 99%; ¹ H NMR (400 MHz, DMSO-d6) δ 10.69 (s, 1H), 7.87-7.94 (m, 2H), 7.44-7.56 (m, 2H), 7.33-7.48 (m, 4H), 7.24-7.33 (m, 1H), 4.62 (s, 1H), 3.65 (s, 3H), 2.54 (s, 3H), 2.35 (s, 1H), 1.49-1.63 (m, 6H). Example 125: 6-(1,3-benzoxazol-2-yl)-5-hydroxy-3-methyl-2-{methyl[phenyl( pyridin-2- yl)methyl]amino} pyrimidin-4-one [00589] Step 1: To a stirred solution of ethyl 2-chloro-5-methoxy-1-methyl-6-oxopyrimidine-4- carboxylate (1.99 g, 8.088 mmol, 1.49 equiv) and 1-phenyl-1-(pyridin-2-yl)methanamine (1 g, 5.428 mmol, 1 equiv) in DMSO (30 mL) was added DIEA (2836.28 µL, 16.284 mmol, 3 equiv) in portions at ambient temperature under air atmosphere. The resulting mixture was stirred overnight at 110 °C under air atmosphere. The reaction was monitored by TLC. Desired product could be detected by TLC. The resulting mixture was diluted with water (100 mL). The resulting mixture was extracted with EtOAc (3 x 50 mL). The combined organic layers were washed with brine (1 x 200 mL), dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE/EA (5:1) to afford ethyl 5-methoxy-1- methyl-6-oxo-2-{[phenyl(pyridin-2-yl)methyl]amino}pyrimidine -4-carboxylate (1.9 g, 89%) as a colorless solid. ES MS M/Z = 219.1 [M+H] ⁺ . [00590] Step 2: To a stirred solution of methyl 5-methoxy-1-methyl-6-oxo-2-{[phenyl(pyridin-2- yl)methyl]amino}pyrimidine-4-carboxylate (1.8 g, 4.732 mmol, 1 equiv) and cesium carbonate (4.02 g, 7.098 mmol, 1.5 equiv) in DMF (20 mL) was added iodomethane (0.29 mL, 4.732 mmol, 1 equiv) in portions at ambient temperature under air atmosphere. The resulting mixture was stirred for 2 h at ambient temperature under air atmosphere. The reaction was monitored by LCMS. The resulting mixture was diluted with water (50 mL). The resulting mixture was extracted with EtOAc (3 x 50 mL). The combined organic layers were washed with brine (1 x 100 mL), dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE/EA (5:1) to afford methyl 5-methoxy-1-methyl-2- {methyl[phenyl(pyridin-2-yl)methyl]amino}-6-oxopyrimidine-4- carboxylate (1.5 g, 72%) as a colorless solid. ES MS M/Z = 409.3 [M+H] ⁺ . [00591] Step 3: A solution of ethyl 5-methoxy-1-methyl-2-{methyl[phenyl(pyridin-2- yl)methyl]amino}-6-oxopyrimidine-4-carboxylate (2 g, 4.90 mmol, 1 equiv) in THF (25 mL) was treated with LiOH (0.58 g, 24.48 mmol, 5 equiv) in H ₂ O (10 mL) for 2 min at 0 °C under nitrogen atmosphere. The resulting mixture was stirred for 30 min at ambient temperature under air atmosphere. The reaction was monitored by LCMS. The mixture was neutralized to pH 3 with HCl (1M.). The resulting mixture was concentrated under vacuum to afford 5-methoxy-1-methyl-2-{methyl[phenyl(pyridin-2- yl)methyl]amino}-6-oxopyrimidine-4-carboxylic acid (1.5 g, 81%) as a brown oil. The crude product was used in the next step directly without further purification. ES MS M/Z =381.5 [M+H] ⁺ . [00592] Step 4: To a stirred solution of 5-ethoxy-1-methyl-2-{methyl[phenyl(pyridin-2- yl)methyl]amino}-6-oxopyrimidine-4-carboxylic acid (1.40 g, 3.694 mmol, 1 equiv) and 2-iodoaniline (0.89 g, 4.048 mmol, 1.1 equiv) in DMF (20 mL) were added Tcfh (2.07 g, 7.360 mmol, 2 equiv) and NMI (0.91 g, 11.040 mmol, 3 equiv) in portions at ambient temperature under air atmosphere. The resulting mixture was stirred overnight at ambient temperature under air atmosphere. The reaction was monitored by LCMS. The resulting mixture was diluted with water (50 mL). The resulting mixture was extracted with EtOAc (3 x 50 mL). The combined organic layers were washed with brine (2 x 100 mL), dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (2: 1) to afford N-(2-iodophenyl)-5-methoxy-1-methyl-2-{methyl[phenyl(pyridin -2-yl)methyl]amino}-6- oxopyrimidine-4-carboxamide (1.1 g, 36%) as a yellow oil. ES MS M/Z =582.2 [M+H] ⁺ . [00593] Step 5: A solution of N-(2-iodophenyl)-5-methoxy-1-methyl-2-{methyl[phenyl(pyridin -2- yl)methyl]amino}-6-oxopyrimidine-4-carboxamide (100 mg, 0.172 mmol, 1 equiv) in Toluene (2 mL) was treated with DMEDA (15 mg, 0.172 mmol, 1 equiv) for 1 min at ambient temperature under nitrogen atmosphere followed by the addition of CuI (4 mg, 0.017 mmol, 0.1 equiv) in portions at ambient temperature. The resulting mixture was stirred overnight at 110 °C under nitrogen atmosphere. The reaction was monitored by LCMS. The resulting mixture was filtered, the mixture was purified by reversed-phase flash chromatography to afford 6-(1,3-benzoxazol-2-yl)-5-methoxy-3-methyl-2- {methyl[phenyl(pyridin-2-yl)methyl]amino}pyrimidin-4-one (50 mg, 64%) as a colorless solid. ES MS M/Z = 454.1 [M+H] ⁺ . [00594] Step 6: To the mixture of 6-(1,3-benzoxazol-2-yl)-5-methoxy-3-methyl-2- {methyl[phenyl(pyridin-2-yl)methyl]amino}pyrimidin-4-one (30 mg, 0.066 mmol, 1 equiv) in DCM (2 mL) was added BBr ₃ (0.13 mL, 0.132 mmol, 2 equiv) in DCM at -78 °C. The mixture was stirred at ambient temperature for 2 h. The mixture was concentrated under reduced pressure. The crude product was purified by Prep-HPLC (Column: Xselect CSH F-Phenyl OBD, 19*250 mm, 5μm; Mobile Phase A: Water(0.1%FA), Mobile Phase B: acetonitrile; Flow rate: 25 mL/min; Gradient: 32% B to 48% B in 7 min, 48% B; Wave Length: 254 nm; RT(min): 6.23) to afford 6-(1,3-benzoxazol-2-yl)-5-hydroxy-3- methyl-2-{methyl[phenyl(pyridin-2-yl)methyl]amino}pyrimidin- 4-one (2.8 mg, 9.35%). ES MS M/Z = 440.1 [M+H] ⁺ ,UPLC: 97%; ¹ H NMR (400 MHz, DMSO-d6) δ 8.44 – 8.43 (m, 1H), 7.87 – 7.85 (m, 1H), 7.72 – 7.52 (m, 6H), 7.49 – 7.12 (m, 5H), 5.82 (s, 1H), 3.72 (s, 3H), 2.68 (s, 3H), 1.24 (s, 1H). Example 126: Methyl (2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6-dih ydropyrimidin- 2-yl)-1-cyclobutyl-1H-benzo[d]imidazol-6-yl)carbamate [00595] Step 1: To a stirred solution of 2-(6-amino-1-cyclobutyl-1,3-benzodiazol-2-yl)-6-(1,3- benzoxazol-2-yl)-5-methoxy-3-methylpyrimidin-4-one (100 mg, 0.226 mmol, 1 equiv) in DCM (5 mL) was added BBr3 (85 mg, 0.339 mmol, 1.5 equiv) dropwise at -60 °C under nitrogen atmosphere. The resulting mixture was stirred for 16 h at ambient temperature under nitrogen atmosphere. The reaction was quenched by the addition of sat. NaHCO3 (aq.) (10 mL) at ambient temperature. The resulting mixture was extracted with DCM (3 x 10 mL). The combined organic layers were washed with brine (10 mL), dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure to afford 2-(6-amino-1-cyclobutyl-1,3-benzodiazol-2-yl)-6-(1,3-benzoxa zol-2-yl)-5-hydroxy-3- methylpyrimidin-4-one (60 mg, 61.96%) as a yellow oil. ES MS M/Z = 529.10 [M+H] ⁺ . [00596] Step 2: A solution of tert-butyl N-{2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6- oxopyrimidin-2-yl]-3-cyclobutyl-1,3-benzodiazol-5-yl}carbama te (100 mg, 0.189 mmol, 1 equiv) in DCM (2 mL) was added TFA (0.4 mL). The mixture was stirred for 1 h at ambient temperature. The resulting mixture was concentrated under reduced pressure. The mixture was basified to pH 8 with saturated NaHCO3 (aq.). The resulting mixture was extracted with DCM (3 x 10 mL). The combined organic layers were washed with brine (10 mL) and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure to afford 2-(6-amino-1-cyclobutyl-1,3-benzodiazol- 2-yl)-6-(1,3-benzoxazol-2-yl)-5-hydroxy-3-methylpyrimidin-4- one (80 mg, 99%) as a yellow solid. ES MS M/Z = 429.10 [M+H] ⁺ . [00597] Step 3: To a stirred mixture of 2-(6-amino-1-cyclobutyl-1,3-benzodiazol-2-yl)-6-(1,3- benzoxazol-2-yl)-5-hydroxy-3-methylpyrimidin-4-one (50 mg, 0.117 mmol, 1 equiv) and methyl chloroformate (11 mg, 0.117 mmol, 1 equiv) in DCM (2 mL) were added TEA (20 µL, 0.140 mmol, 1.2 equiv) dropwise at 0 °C. The resulting mixture was stirred for 30 min at ambient temperature. The resulting mixture was concentrated under reduced pressure. The resulting mixture was diluted with toluene (1 mL) and water (1mL). The resulting mixture was stirred for 2 days at 80 °C then concentrated under reduced pressure. The crude product (50 mg) was purified by Prep-HPLC (Column: Sunfire prep C ₁₈ column, 30*150 mm, 5μm; Mobile Phase A: Water(0.1%FA), Mobile Phase B: acetonitrile; Flow rate: 60 mL/min; Gradient: 35% B to 65% B in 7 min, 65% B; Wave Length: 254 nm; RT(min): 6.88; Injection Volume: 0.5 mL) to afford methyl N-{2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6- oxopyrimidin-2-yl]-3-cyclobutyl-1,3-benzodiazol-5-yl}carbama te (2.0 mg, 3.5%). ES MS M/Z = 487.10 ^{[M+H]+, UPLC: 99%; 1H NMR (300 MHz, DMSO-d} 6 ^{) δ 9.87 (s, 1H), 8.22 (s, 1H), 7.93-7.78 (m, 2H),} 7.69 (d, J = 8.8 Hz, 1H), 7.55-7.44 (m, 2H), 7.35 (m, J = 8.9, 1.8 Hz, 1H), 5.24 (t, J = 8.7 Hz, 1H), 3.73 (s, 3H), 3.56 (s, 3H), 2.67 (d, J = 9.4 Hz, 2H), 2.41-2.49 (m, 2H), 1.86 – 1.82 (m, 2H). Example 127: 6-(1,3-benzoxazol-2-yl)-2-[1-cyclobutyl-6-(5-oxo-4H-1,2,3,4- tetrazol-1-yl)-1,3- benzodiazol-2-yl]-5-hydroxy-3-methylpyrimidin-4-one [00598] Step 1: To the mixture of 2-(6-amino-1-cyclobutyl-1,3-benzodiazol-2-yl)-6-(1,3-benzoxa zol-2- yl)-5-methoxy-3-methylpyrimidin-4-one (90 mg, 0.203 mmol, 1 equiv) and triphosgene (60 mg, 0.203 mmol, 1 equiv) in DCM (2 mL) was added TEA (24 mg, 0.244 mmol, 1.2 equiv) at 0 °C. The mixture was stirred at ambient temperature for 2 h. The mixture was concentrated. The residue was dissolved by toluene. To the mixture was added azidotrimethylsilane (25 mg, 0.22 mmol, 1.1 equiv). The mixture was stirred at ambient temperature for 16 h then concentrated. The residue was purified by reversed-phase flash chromatography (column, C18 silica gel; mobile phase, acetonitrile in Water (0.05% TFA), 20% to 70% gradient in 20 min; detector, UV 254 nm) to afford 6-(1,3-benzoxazol-2-yl)-2-[1-cyclobutyl-6-(5- oxo-4H-1,2,3,4-tetrazol-1-yl)-1,3-benzodiazol-2-yl]-5-methox y-3-methylpyrimidin-4-one (60 mg, 57.67%) as a yellow solid. ES MS M/Z = 512.3 [M+H] ⁺ . [00599] Step 2: To the mixture of 6-(1,3-benzoxazol-2-yl)-2-[1-cyclobutyl-6-(5-oxo-4H-1,2,3,4- tetrazol-1-yl)-1,3-benzodiazol-2-yl]-5-methoxy-3-methylpyrim idin-4-one (60 mg, 0.117 mmol, 1 equiv) in DCM (2 mL) was added BBr3 in DCM (0.59 mL, 0.585 mmol, 5 equiv) at -78°C. The mixture was stirred at ambient temperature for 1 h then quenched by MeOH (3 mL) at 0°C. The mixture was concentrated under reduced pressure. The crude product was purified by Prep-HPLC with the following conditions (Column: XSelect CSH Prep C18 OBD Column, 19*150 mm, 5μm; Mobile Phase A: Water(0.1%FA), Mobile Phase B: acetonitrile; Flow rate: 25 mL/min; Gradient: 39% B to 69% B in 7 min, 69% B; Wave Length: 254 nm; RT(min): 6.88; Injection Volume: 0.5 mL) to afford 6-(1,3- benzoxazol-2-yl)-2-[1-cyclobutyl-6-(5-oxo-4H-1,2,3,4-tetrazo l-1-yl)-1,3-benzodiazol-2-yl]-5-hydroxy-3- methylpyrimidin-4-one (12.8 mg, 21%). ES MS M/Z = 498.2 [M+H] ⁺ , UPLC: 95%; ¹ H NMR (400 MHz, DMSO-d6) δ 10.49 (s, 1H), 8.29 (d, J = 1.9 Hz, 1H), 7.97 – 7.84 (m, 2H), 7.75 (d, J = 8.8 Hz, 1H), 7.55 – 7.40 (m, 3H), 5.30 - 5.20 (m, 1H), 3.55 (s, 3H), 2.73 - 2.62 (m, 2H), 2.48 - 2.41 (m, 2H), 1.96 – 1.73 (m, 2H). Example 128: 2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyrimidin -2-yl]-3-cyclobutyl- 1,3-benzodiazole-5-carboxylic acid [00600] To the mixture of methyl 2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyrimidin -2- yl]-3-cyclobutyl-1,3-benzodiazole-5-carboxylate (40 mg, 0.085 mmol, 1 equiv) in THF (2.00 mL) was added NaOH (17 mg, 0.425 mmol, 5 equiv) in H2O (0.1 mL). The mixture was stirred at ambient temperature for 16h. The mixture was acidified to pH 4 with HCl (2M). The product was precipitated by the addition of water (10 mL). The precipitated solids were collected by filtration and washed with Et ₂ O (3 x 3 mL) to afford 2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyrimidin -2-yl]-3-cyclobutyl- 1,3-benzodiazole-5-carboxylic acid (8.0 mg, 20%). ES MS M/Z = 458.05 [M+H] ⁺ , UPLC: 97%; ¹ NMR (400 MHz, DMSO-d6) δ 13.08 (s, 1H), 11.62 (s, 1H), 8.41 (d, J = 3.0 Hz, 1H), 8.01 – 7.78 (m, 4H), 7.52 - 7.45 (m, 2H), 5.35 - 5.23 (m, 1H), 3.56 (s, 3H), 2.73 – 2.58 (m, 2H), 2.47 - 2.42 (m, 2H), 1.94 – 1.77 (m, 2H). Example 129: N-{2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyrimi din-2-yl]-3- cyclobutyl-1,3-benzodiazol-5-yl}acetamide

[00601] Step 1: A solution of 3-fluoro-4-nitroaniline (10 g, 64.055 mmol, 1 equiv) and di-tert-butyl dicarbonate (13.98 g, 64.06 mmol, 1.00 equiv) and DMAP (0.78 g, 6.41 mmol, 0.1 equiv) in DCM (150 mL) was stirred for 3 days at ambient temperature under nitrogen atmosphere. The resulting mixture was extracted with DCM (3 x 400 ml). The combined organic layers were washed with brine (200 mL), dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column EA:PE = 1:5 to afford tert-butyl N-(3-fluoro-4-nitrophenyl) carbamate (7 g, 42.65%) as a yellow solid. ES MS M/Z = 257.10 [M+H] ⁺ . [00602] Step 2: A solution of tert-butyl N-(3-fluoro-4-nitrophenyl)carbamate (2 g, 7.805 mmol, 1.5 equiv) and cyclobutylamine (370 mg, 5.203 mmol, 1 equiv) and DIEA (1345.10 mg, 10.407 mmol, 2 equiv) in NMP (20 mL) was stirred for 15 h at 105 °C. To the mixture was added H2O (50 mL), The mixture was extracted with EA (3 x 300ml). The combined organic layers were washed with NaCl (1 x 200ml), dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (10:1) to afford tert-butyl N-[3-(cyclobutylamino)-4-nitrophenyl]carbamate (1.3 g, 82%) as a yellow solid. ES MS M/Z = 308.10 [M+H] ⁺ . [00603] Step 3: A solution of tert-butyl N-[3-(cyclobutylamino)-4-nitrophenyl]carbamate (1.8 g, 5.857 mmol, 1 equiv) in MeOH (20 mL) was added Pd/C (0.19 g, 1.757 mmol, 0.3 equiv) . The mixture was stirred at ambient temperature for 16 h under hydrogen atmosphere. The resulting mixture was filtered, the filter cake was washed with MeOH (3 x 20 mL). The filtrate was concentrated under reduced pressure. This resulted in tert-butyl N-[4-amino-3-(cyclobutylamino)phenyl]carbamate (1.5 g, 92%) as a purple solid. ES MS M/Z = 278.10 [M+H] ⁺ . [00604] Step 4: To the mixture of 4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxopyrimidine-2 - carbaldehyde (300 mg, 1.052 mmol, 1 equiv) in DMF (10 mL) and H2O (5 mL) was added tert-butyl N- [4-amino-3-(cyclobutylamino)phenyl]carbamate (292 mg, 1.052 mmol, 1 equiv) and oxone (177 mg, 1.052 mmol, 1 equiv). The mixture was stirred at ambient temperature for 2h. The resulting mixture was diluted with water (20 mL). The resulting mixture was extracted with EtOAc (3 x 20 mL). The combined organic layers were washed with brine (20 mL), dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by Prep-TLC (PE / EA 1:1) to afford tert-butyl N-{2-[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxopyrimi din-2-yl]-3-cyclobutyl- 1,3-benzodiazol-5-yl}carbamate (110 mg, 19%) as a yellow crystal. ES MS M/Z = 543.10 [M+H] ⁺ . [00605] Step 5: A mixture of tert-butyl N-{2-[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6- oxopyrimidin-2-yl]-3-cyclobutyl-1,3-benzodiazol-5-yl}carbama te (100 mg, 0.184 mmol, 1 equiv) in TFA (0.5 mL) and DCM (2 mL). The mixture was stirred for 1 h at ambient temperature. The mixture was basified to pH 8 with saturated NaHCO3 (aq.). The resulting mixture was extracted with DCM (3 x 30 mL). The combined organic layers were washed with brine (50 mL), dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure to afford the crude product 2-(6-amino-1-cyclobutyl-1,3-benzodiazol-2-yl)-6-(1,3-benzoxa zol-2-yl)-5-methoxy-3-methylpyrimidin- 4-one (70 mg, 86%) as a yellow solid. ES MS M/Z = 443.18 [M+H] ⁺ . [00606] Step 6: A solution of 2-(6-amino-1-cyclobutyl-1,3-benzodiazol-2-yl)-6-(1,3-benzoxa zol-2-yl)- 5-methoxy-3-methylpyrimidin-4-one (50 mg, 0.113 mmol, 1 equiv) in DCM (2 mL) was added AcCl (18 mg, 0.226 mmol, 2 equiv) and TEA (23 mg, 0.226 mmol, 2 equiv) in portions at ambient temperature. The resulting mixture was stirred for 1 h at ambient temperature. The residue was purified by Prep-TLC (PE / EA 1:1) to afford N-{2-[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxopyrimi din-2-yl]-3- cyclobutyl-1,3-benzodiazol-5-yl}acetamide (45 mg, 82.19%) as a yellow solid. ES MS M/Z = 485.10 [M+H] ⁺ . [00607] Step 7: A mixture of N-{2-[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxopyrimi din-2- yl]-3-cyclobutyl-1,3-benzodiazol-5-yl}acetamide (40 mg, 0.083 mmol, 1 equiv) and LiBr (36 mg, 0.415 mmol, 5 equiv) in DMF (1 mL). The mixture was stirred for 16 h at 100 °C. Desired products could be detected by LCMS. The resulting mixture was diluted with water (5 mL). The residue was purified by trituration with water (5 mL). The precipitated solids were collected by filtration and washed with hexane (3 x 5 mL) to afford N-{2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyrimi din-2-yl]-3- cyclobutyl-1,3-benzodiazol-5-yl}acetamide (3.1 mg, 8%) as a brown solid. ES MS M/Z = 471.10 [M+H] ⁺ ; ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 10.10 (s, 1H), 8.33 (s, 1H), 7.63 - 7.54 (m, 3H), 7.37 – 7.28 (m, 3H), 5.15 - 5.10 (m, 1H), 3.45 (s, 3H), 2.62 (t, J = 10.2 Hz, 2H), 2.42 (s, 2H), 2.09 (s, 3H), 1.83 - 1.81 (m, 2H), 1.22 (s, 3H). [00608] The following compounds were synthesized in a similar manner: Example 130: 6-(1,3-benzoxazol-2-yl)-2-(1-{bicyclo[1.1.1] pentan-1-yl}-1,3-benzodiazol-2-yl)-5- hydroxy-3-methylpyrimidin-4-one [00609] ES MS M/Z = 426.00 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d6) δ 7.23 – 7.77 (m, 9H), 3.27 (s, 3H), 2.32 (s, 4H), 1.97 (s, 3H). Example 131: Methyl 2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyrimidin -2-yl]-3- cyclobutyl-1,3-benzodiazole-5-carboxylate [00610] ES MS M/Z = 413.1 [M+H] ⁺ , UPLC: 95%; ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 12.60 - 11.01 (br, 1H), 8.42 (d, J = 3.0 Hz, 1H), 8.01 - 7.79 (m, 4H), 7.57 - 7.42 (m, 2H), 5.36 - 5.22 (m, 1H), 3.94 (s, 3H), 3.58 (s, 3H), 2.74 - 2.54 (m, 2H), 2.42 - 2.40 (m, 2H), 1.90 - 1.71 (m, 2H). Example 132: 6-(benzo[d]oxazol-2-yl)-5-hydroxy-3-methyl-2-(1-(3-methyloxe tan-3-yl)-1H- benzo[d]imidazol-2-yl)pyrimidin-4(3H)-one _[00611] ES MS M/Z 430.05 [M+H] ⁺ , UPLC: 97.0%; ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 7.87 - 7.72 (m, 1H), 7.72 - 7.49 (m, 2H), 7.47 - 7.11 (m, 4H), 4.83 (d, J = 6.0 Hz, 2H), 4.59 (s, 2H), 3.71 (s, 3H), 2.37 (s, 3H), 2.08 - 1.89 (m, 1H), 1.22 (s, 3H). Example 133: 6-(1,3-benzoxazol-2-yl)-2-(1-cyclobutylindol-2-yl)-5-hydroxy -3-methylpyrimidin-4- one [00612] Step 1: Into a 2 L 3-necked round-bottom flask were added EtOH (600 mL), sodium ethanolate (31.68 g, 465.581 mmol, 1.1 equiv) and ethyl oxalate (68.04 g, 465.6 mmol, 1.1 equiv) at ambient temperature. This was followed by addition of ethyl 2-methoxyacetate (50 g, 423.255 mmol, 1 equiv) dropwise with stirring at ambient temperature under nitrogen atmosphere. The resulting mixture was stirred overnight at ambient temperature under nitrogen atmosphere. The reaction was monitored by LCMS. The resulting mixture was concentrated under vacuum to remove most of ethanol. The mixture was acidified to pH 3 with HCl (1M) at 0 °C. The resulting mixture was extracted with EtOAc (3 x 500 mL). The combined organic layers were washed with brine (1 x 500 mL), dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure to afford 1,4-diethyl 2- methoxy-3-oxobutanedioate (80 g, 87%) as a light yellow oil. ES MS M/Z = 219.1 [M+H] ⁺ . [00613] Step 2: Into a 2 L round-bottom flask were added 1,4-diethyl 2-methoxy-3-oxobutanedioate (80 g, 366.628 mmol, 1 equiv), methylurea (27.16 g, 366.628 mmol, 1 equiv), AcOH (900 mL) and HCl(gas)in 1,4-dioxane (300 mL) at ambient temperature. The resulting mixture was stirred for 3 h at 105°C under air atmosphere. The resulting mixture was concentrated under vacuum. The residue was washed with hexane (1 x 500 mL). This resulted in ethyl 2-methoxy-2-[(4E)-1-methyl-2,5- dioxoimidazolidin-4-ylidene]acetate (85 g, 91%) as a brown solid. ES MS M/Z = 229.1 [M+H] ⁺ . [00614] Step 3: Into a 2 L round-bottom flask were added ethyl 2-methoxy-2-[(4E)-1-methyl-2,5- dioxoimidazolidin-4-ylidene]acetate (85 g, 372.474 mmol, 1 equiv) and KOH (1000 mL) at ambient temperature. The resulting mixture was stirred for 3 h at 105 °C under air atmosphere. The mixture was allowed to 0 °C. The mixture was neutralized to pH 3 with conc. HCl. The resulting mixture was extracted with EtOAc (3 x 1000 mL). The combined organic layers were washed with brine (1 x 1000 mL), dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by trituration with diethyl ether (500 mL). This resulted in 2-hydroxy- 5-methoxy-1-methyl-6-oxopyrimidine-4-carboxylic acid (25 g, 34%) as a colorless solid. ES MS M/Z = 201.2 [M+H] ⁺ . [00615] Step 4: Into a 250 mL 3-necked round-bottom flask were added 2-hydroxy-5-methoxy-1- methyl-6-oxopyrimidine-4-carboxylic acid (20 g, 99.925 mmol, 1 equiv) and EtOH (400 mL) at °C. This was followed by the addition of AcCl (106.97 mL, 1498.875 mmol, 15 equiv) dropwise with stirring at 0 °C. The resulting mixture was stirred overnight at 90 °C under argon atmosphere. The mixture was allowed to cool down to 0 °C. The precipitated solids were collected by filtration and washed with EtOH (2 x 200 mL). This resulted in ethyl 2-hydroxy-5-methoxy-1-methyl-6-oxopyrimidine-4-carboxylate (16.3 g, 70%) as a colorless solid. ES MS M/Z = 229.1 [M+H] ⁺ . [00616] Step 5: Into a 500 mL 3-necked round-bottom flask were added ethyl 2-hydroxy-5-methoxy-1- methyl-6-oxopyrimidine-4-carboxylate (16 g, 70.113 mmol, 1 equiv) and POCl3 (320 mL) at ambient temperature. The resulting mixture was stirred overnight at 100 °C under nitrogen atmosphere. The reaction was monitored by LCMS. The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE/EA (4 : 1) to afford ethyl 2- chloro-5-methoxy-1-methyl-6-oxopyrimidine-4-carboxylate (9.5 g, 53%) as a yellow solid. ES MS M/Z = 247.1 [M+H] ⁺ . [00617] Step 6: A solution of indole (5 g, 42.680 mmol, 1 equiv) and KOH (4.79 g, 85.360 mmol, 2 equiv) in DMF (55 mL) was added with KOH (4.79 g, 85.360 mmol, 2 equiv). The mixture was stirred for 5 h at 80 °C under air atmosphere. The reaction was monitored by LCMS. The precipitated solids were collected by filtration and the resulting mixture was diluted with water (100 mL). The resulting mixture was extracted with EtOAc (3 x 100 mL). The combined organic layers were washed with brine (1 x 200 mL), dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford 1-cyclobutylindole (4 g, 49%) as a colorless solid. ES MS M/Z = 172.1 [M+H] ⁺ . [00618] Step 7: To the mixture of 1-cyclobutylindole (3.8 g, 22.191 mmol, 1 equiv) in THF (100 mL) was added sec-BuLi (34.14 mL, 44.38 mmol, 2 equiv) at -78 °C slowly under nitrogen atmosphere. The mixture was stirred at the -40 °C for 1h. To the mixture was added 2-isopropoxy-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane (4.13 g, 22.191 mmol, 1 equiv) at -78°C. The mixture was warmed to ambient temperature and stirred at ambient temperature for 2h. To the mixture was added H ₂ O (100 mL) and extracted by EtOAc (100 mL x 3). The organic layer was combined, washed by brine (200 mL), dried over sodium sulfate, filtered, and concentrated to afford 1-cyclobutyl-2-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)indole (5 g, 76%) as yellow oil. The crude product was used in the next step directly without further purification. ES MS M/Z = 298.2 [M+H] ⁺ . [00619] Step 8: To the mixture of ethyl 2-chloro-5-methoxy-1-methyl-6-oxopyrimidine-4-carboxylate (1.5 g, 6.081 mmol, 1 equiv) and 1-cyclobutyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) indole (4.52 g, 15.203 mmol, 2.5 equiv) in dioxane (60.00 mL) was added Pd2(dba)3 (0.33 g, 0.365 mmol, 0.06 equiv) , tri-tert-butylphosphine tetrafluoroborate (211 mg, 0.730 mmol, 0.12 equiv) and KF (39 mg, 0.670 mmol, 3.3 equiv). The mixture was stirred at 135°C for 16h under nitrogen atmosphere. The mixture was filtered. The filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography (column, C18 silica gel; mobile phase, acetonitrile in Water (0.1% TFA), 30% to 100% gradient in 30 min; detector, UV 254 nm) to afford ethyl 2-(1-cyclobutylindol-2-yl)- 5-methoxy-1-methyl-6-oxopyrimidine-4-carboxylate (300 mg, 13%) as black oil. ES MS M/Z = 382.1 [M+H] ⁺ . [00620] Step 9: To the mixture of ethyl 2-(1-cyclobutylindol-2-yl)-5-methoxy-1-methyl-6- oxopyrimidine-4-carboxylate (280 mg, 0.734 mmol, 1 equiv) in THF (5 mL) was added LiOH (105 mg, 4.404 mmol, 6 equiv) in H ₂ O (0.2 mL). The mixture was stirred at ambient temperature for 4h. The mixture was concentrated to remove THF. The residue was acidified to pH 4 with HCl (2 M). The mixture was extracted by EtOAc (5 mL x 3). The organic layer was washed by brine (10 mL), dried over sodium sulfate, filtered, and concentrated to afford 2-(1-cyclobutylindol-2-yl)-5-methoxy-1-methyl-6- oxopyrimidine-4-carboxylic acid (200 mg, 77%) as brown oil. ES MS M/Z = 354.1 [M+H] ⁺ . [00621] Step 10: The mixture of 2-(1-cyclobutylindol-2-yl)-5-methoxy-1-methyl-6-oxopyrimidin e-4- carboxylic acid (100 mg, 0.283 mmol, 1 equiv) and HATU (215 mg, 0.566 mmol, 2 equiv) in THF (5 mL) was stirred at ambient temperature for 2 min. The mixture was added with DIEA (55 mg, 0.424 mmol, 1.5 equiv) and stirred at ambient temperature for 2 min, and 2-aminophenol (46 mg, 0.42 mmol, 1.5 equiv) was added. The mixture was stirred at 65°C for 16 h. The mixture was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography (column, C18 silica gel; mobile phase, acetonitrile in Water (0.05% TFA), 30% to 100% gradient in 20 min; detector, UV 254 nm) to afford 2-(1-cyclobutylindol-2-yl)-N-(2-hydroxyphenyl)-5-methoxy-1-m ethyl-6- oxopyrimidine-4-carboxamide (40 mg, 32%) as brown oil. ES MS M/Z = 445.1 [M+H] ⁺ . [00622] Step 11: To the mixture of 2-(1-cyclobutylindol-2-yl)-N-(2-hydroxyphenyl)-5-methoxy-1- methyl-6-oxopyrimidine-4-carboxamide (40 mg, 0.090 mmol, 1 equiv) in NMP (3 mL) was added P ₂ O ₅ (51 mg, 0.360 mmol, 4 equiv) and TsOH (62 mg, 0.360 mmol, 4 equiv) at 200°C. Desired products could be detected by LCMS. The mixture was purified by Prep-HPLC (Column: XSelect CSH Prep C18 OBD Column, 19*150 mm, 5μm; Mobile Phase A: Water(0.1%FA), Mobile Phase B: acetonitrile: THF=1:1; Flow rate: 25 mL/min; Gradient: 40% B to 55% B in 10 min, 55% B; Wave Length: 254 nm; RT(min): 7.97/8.8; Injection Volume: 0.46 mL) to afford 6-(1,3-benzoxazol-2-yl)-2-(1-cyclobutylindol-2-yl)-5- hydroxy-3-methylpyrimidin-4-one (4.1 mg, 14.29%). ES MS M/Z = 413.10 [M+H] ⁺ , UPLC: 98%; ¹ H NMR (300 MHz, DMSO-d6) δ 11.25 (br, 1H), 7.90 - 7.65 (m, 4H), 7.52 - 7.40 (m, 2H), 7.30 - 7.10 (m, 2H), 6.83 (s, 1H), 5.08 - 4.92 (m, 1H), 3.42 (s, 3H), 2.70 - 2.60 (m, 2H), 2.40 - 2.30 (m, 2H), 1.89 - 1.69 (m, 2H). [00623] The following compounds were synthesized in a similar manner: Example 134: 6-(5-chloro-1,3-benzoxazol-2-yl)-2-(1-cyclobutyl-1,3-benzodi azol-2-yl)-5-hydroxy-3- methylpyrimidin-4-one [00624] ES MS M/Z = 525.1 [M+H] ⁺ , UPLC: 99%; ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 11.56 (s, 1H), 8.00 (d, J = 1.8 Hz, 1H), 7.87 - 7.91 (m, 1H), 7.82 - 7.84 (m, 1H), 7.77 - 7.80 (m, 1H), 7.50 - 7.53 (m, 1H), 7.32 - 7.43 (m, 2H), 5.16 - 5.28 (m, 1H), 3.54 (s, 3H), 2.61 - 2.71 (m, 2H), 2.42 - 2.45 (m, 2H), 1.73 - 1.93 (m, 2H). Example 135: 6-(6-chloro-1,3-benzoxazol-2-yl)-2-(1-cyclobutyl-1,3-benzodi azol-2-yl)-5-hydroxy-3- methylpyrimidin-4-one [00625] ES MS M/Z = 448.0 [M+H] ⁺ , UPLC: 96%; ¹ H NMR (300 MHz, DMSO-d6) δ 8.04 (d, J = 1.8 Hz, 1H), 7.87 - 7.92 (m, 2H), 7.77 - 7.80 (m, 1H), 7.48 - 7.52 (m, 1H), 7.32 - 7.44 (m, 2H), 5.16 - 5.27 (m, 1H), 3.54 (s, 3H), 2.61 - 2.72 (m, 2H), 2.42 (s, 2H), 1.72 - 1.89 (m, 2H). Example 136: 2-(1-cyclobutyl-1,3-benzodiazol-2-yl)-5-hydroxy-6-(4-methoxy -1,3-benzoxazol-2-yl)- 3-methylpyrimidin-4-one [00626] ES MS M/Z = 444.10 [M+H] ⁺ , UPLC: 99%; ¹ H NMR (300 MHz, DMSO-d6) δ 7.87 (d, J = 7.7 Hz, 1H), 7.77 (d, J = 7.7 Hz, 1H), 7.37 – 7.27 (m, 4H), 6.92 (s, 1H), 5.32 – 5.19 (m, 1H), 3.97 (s, 3H), 3.59 – 3.33 (m, 3H), 2.67 (d, J = 10.3 Hz, 2H), 2.54 (s, 2H), 1.83 (s, 2H). Example 137: 6-(4-chlorobenzo[d]oxazol-2-yl)-2-(1-cyclobutyl-1H-benzo[d]i midazol-2-yl)-5- hydroxy-3-methylpyrimidin-4(3H)-one [00627] ES MS M/Z 448.00 [M+H] ⁺ , UPLC: 97%; ¹ H NMR (300 MHz, DMSO-d6) δ 11.61 (s, 1H), 7.93 (d, J = 8.5 Hz, 1H), 7.82 (t, J = 7.4, 3.7 Hz, 2H), 7.65 - 7.30 (m, 4H), 5.36 - 5.18 (m, 1H), 3.57 (d, J = 3.3 Hz, 3H), 2.70 (q, J = 9.1 Hz, 2H), 2.49 - 2.30 (m, 2H), 1.83 (t, J = 29.0, 9.7 Hz, 2H). Example 138: 2-(1-cyclobutyl-1,3-benzodiazol-2-yl)-5-hydroxy-6-(5-methoxy -1,3-benzoxazol-2-yl)- 3-methylpyrimidin-4-one [00628] ES MS M/Z 444.10 [M+H] ⁺ , UPLC: 99.3%; ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 11.47 (s, 1H), 7.91 (d, J = 8.0 Hz, 1H), 7.80 (dd, J = 7.6, 1.5 Hz, 1H), 7.73 (d, J = 8.9 Hz, 1H), 7.51 - 7.32 (m, 3H), 7.08 (dd, J = 9.0, 2.6 Hz, 1H), 5.24 (p, J = 8.8 Hz, 1H), 3.85 (s, 3H), 3.55 (s, 3H), 2.67 (d, J = 10.3 Hz, 2H), 2.47 - 2.18 (m, 2H), 1.99 - 1.68 (m, 2H). Example 139: 2-(1-cyclobutyl-1,3-benzodiazol-2-yl)-5-hydroxy-3-methyl-6-( 4,5,6,7-tetrahydro-1,3- benzoxazol-2-yl)pyrimidin-4-one [00629] Step 1: A solution of 2-(1-cyclobutyl-1,3-benzodiazol-2-yl)-5-hydroxy-1-methyl-6- oxopyrimidine-4-carboxylic acid (500 mg, 1.469 mmol, 1 equiv) in THF (10 mL) was treated with HATU (1.1 g, 2.938 mmol, 2 equiv) for 2 min at ambient temperature under air atmosphere followed by the addition of 2-aminocyclohexan-1-one (199 mg, 1.763 mmol, 1.2 equiv) and DIEA (283 mg, 2.204 mmol, 1.5 equiv) in portions at ambient temperature. The resulting mixture was stirred for an additional 16 h at 65 °C. The reaction was monitored by LCMS. The resulting mixture was concentrated under reduced pressure. The residue was dissolved in acetonitrile (5 mL). The residue was purified by reversed- phase flash chromatography (column, C18 silica gel; mobile phase, acetonitrile in Water (0.1% TFA), 20% to 60% gradient in 30 min; detector, UV 254 nm). This resulted in 2-(1-cyclobutyl-1,3-benzodiazol- 2-yl)-5-hydroxy-1-methyl-6-oxo-N-(2-oxocyclohexyl)pyrimidine -4-carboxamide (250 mg, 39%) as a brown oil. ES MS M/Z = 436.2 [M+H] ⁺ . [00630] Step 2: To a stirred mixture of 2-(1-cyclobutyl-1,3-benzodiazol-2-yl)-5-hydroxy-1-methyl-6- oxo-N-(2-oxocyclohexyl)pyrimidine-4-carboxamide (300 mg, 0.689 mmol, 1 equiv) in DMF (6 mL) was added K2CO3 (190 mg, 1.378 mmol, 2 equiv) and CH3I (147 mg, 1.033 mmol, 1.5 equiv) in portions at ambient temperature under air atmosphere. The resulting mixture was stirred overnight at ambient temperature. The reaction was monitored by LCMS. The resulting mixture was filtered; the filter cake was washed with EA (2 x 3 mL). The filtrate was concentrated under reduced pressure. The residue was dissolved in DMF (3 mL). The residue was purified by reversed-phase flash chromatography (column, C18 silica gel; mobile phase, acetonitrile in Water (0.1% TFA), 10% to 50% gradient in 30 min; detector, UV 254 nm). This resulted in 2-(1-cyclobutyl-1,3-benzodiazol-2-yl)-5-methoxy-1-methyl-6-o xo-N-(2- oxocyclohexyl)pyrimidine-4-carboxamide (134 mg, 43.27%) as a brown oil. ES MS M/Z = 450.2 [M+H] ⁺ . [00631] Step 3: To a stirred solution of 2-(1-cyclobutyl-1,3-benzodiazol-2-yl)-5-methoxy-1-methyl-6- oxo-N-(2-oxocyclohexyl)pyrimidine-4-carboxamide (80 mg, 0.178 mmol, 1 equiv) in CH3CN (2 mL, 38.048 mmol, 213.79 equiv) was added POCl3 (273 mg, 1.78 mmol, 10 equiv) at ambient temperature under nitrogen atmosphere. The resulting mixture was stirred for 16 h at ambient temperature under nitrogen atmosphere. The resulting mixture was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography (column, C18 silica gel; mobile phase, acetonitrile in Water (0.1% TFA), 20% to 80% gradient in 20 min; detector, UV 254 nm) to afford 2-(1-cyclobutyl-1,3- benzodiazol-2-yl)-5-methoxy-3-methyl-6-(4,5,6,7-tetrahydro-1 ,3-benzoxazol-2-yl)pyrimidin-4-one (30 mg, 39%) as a yellow oil. ES MS M/Z = 432.1 [M+H] ⁺ . [00632] Step 4: To a solution of 2-(1-cyclobutyl-1,3-benzodiazol-2-yl)-5-methoxy-3-methyl-6- (4,5,6,7-tetrahydro-1,3-benzoxazol-2-yl)pyrimidin-4-one (30 mg, 0.070 mmol, 1 equiv) in DMF (2 mL, 25.84 mmol, 371.71 equiv) was added LiBr (60.38 mg, 0.700 mmol, 10 equiv). The mixture was stirred at 100 °C for 16 h. The crude product (30 mg) was purified by Prep-HPLC with the following conditions (Column: XBridge Shield RP18 OBD Column, 30*150 mm, 5μm; Mobile Phase A: Water(0.1%FA), Mobile Phase B: acetonitrile; Flow rate: 60 mL/min; Gradient: 31% B to 61% B in 7 min, 61% B to 61% B in 9 min, 61% B; Wave Length: 254 nm; RT(min): 8.88; Injection Volume: 0.7 mL) to afford 2-(1- cyclobutyl-1,3-benzodiazol-2-yl)-5-hydroxy-3-methyl-6-(4,5,6 ,7-tetrahydro-1,3-benzoxazol-2- yl)pyrimidin-4-one (4.1 mg, 14%) as a dark blue solid. ES MS M/Z = 418.1 [M+H] ⁺ , UPLC: NMR (300 MHz, DMSO-d6) δ 7.88 (d, J = 7.6 Hz, 1H), 7.79 (d, J = 7.6 Hz, 1H), 7.32 - 7.44 (m, 2H), 5.11 - 5.22 (m, 1H), 3.50 (s, 3H), 2.60 - 2.67 (m, 6H), 2.50 - 2.57 (m, 2H), 1.79 - 1.83 (m, 6H). Example 140: 2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyrimidin -2-yl]-3-cyclobutyl-N- methyl-1,3-benzodiazole-5-carboxamide [00633] Step 1: To the mixture of methyl 2-[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6- oxopyrimidin-2-yl]-3-cyclobutyl-1,3-benzodiazole-5-carboxyla te (280 mg, 0.577 mmol, 1 equiv) in CH3CN (5 mL) was added sodium trimethylsilonoate (0.87 mL, 0.87 mmol, 1.5 equiv) in H2O (0.02 mL, 1.110 mmol, 107.8 equiv). The mixture was stirred at ambient temperature for 4 h. The mixture was concentrated to remove CH ₃ CN. To the residue was added EtOAc (10 mL) and HCl (10 mL). The organic layer was washed by brine (10mL), dried over sodium sulfate, filtered, and concentrated to afford 2-[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxopyrimidin -2-yl]-3-cyclobutyl-1,3-benzodiazole-5- carboxylic acid (150 mg, 55.17%) as brown oil. ES MS M/Z = 472.2 [M+H] ⁺ . [00634] Step 2: To the mixture of 2-[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxopyrimidin -2- yl]-3-cyclobutyl-1,3-benzodiazole-5-carboxylic acid (100 mg, 0.212 mmol, 1 equiv) in DMF (5 mL) was added HATU (161 mg, 0.424 mmol, 2 equiv), methylamine (7 mg, 0.212 mmol, 1 equiv), DIEA (7 mg, 0.053 mmol, 2.5 equiv). The mixture was stirred at ambient temperature for 2h. The residue was purified by reversed-phase flash chromatography (column, C18 silica gel; mobile phase, acetonitrile in Water (0.05% TFA), 20% to 70% gradient in 30 min; detector, UV 254 nm) to afford 2-[4-(1,3-benzoxazol-2- yl)-5-methoxy-1-methyl-6-oxopyrimidin-2-yl]-3-cyclobutyl-N-m ethyl-1,3-benzodiazole-5-carboxamide (50 mg, 49%) as a yellow solid. ES MS M/Z = 485.2 [M+H] ⁺ . [00635] Step 3: To the mixture of 2-[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxopyrimidin -2- yl]-3-cyclobutyl-N-methyl-1,3-benzodiazole-5-carboxamide (50 mg, 0.103 mmol, 1 equiv) in DMF (2 mL) was added LiBr (54 mg, 0.618 mmol, 6 equiv). The mixture was stirred at 100 °C for 4h. The mixture was purified by Prep-HPLC with the following conditions (Column: XSelect CSH Prep C18 OBD Column, 19*250 mm, 5μm; Mobile Phase A: Water(0.1%FA), Mobile Phase B: acetonitrile; Flow rate: 25 mL/min; Gradient: 34% B to 64% B in 7 min, 64% B; Wave Length: 254 nm; RT(min): 6.97; Injection Volume: 0.8 mL) to afford 2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyrimidin -2- yl]-3-cyclobutyl-N-methyl-1,3-benzodiazole-5-carboxamide (3.6 mg, 7%). ES MS M/Z = 471.2 [M+H] ⁺ , UPLC: 95%; ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 11.88 - 11.10 (br, 1 H), 8.65 (d, J = 4.8 Hz, 1H), 8.32 (s, 1H), 7.93 – 7.79 (m, 4H), 7.57 – 7.42 (m, 2H), 5.30 - 5.20 (m, 1H), 3.56 (s, 3H), 2.87 (d, J = 4.4 Hz, 3H), 2.84 – 2.64 (m, 2H), 2.54 - 2.50 (m, 2H), 1.91 - 1.72 (m, 2H). Example 141: 1-{2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyrimi din-2-yl]-3-cyclobutyl- 1,3-benzodiazol-5-yl}-3-methylurea [00636] Step 1: To a stirred mixture of 2-(6-amino-1-cyclobutyl-1,3-benzodiazol-2-yl)-6-(1,3- benzoxazol-2-yl)-5-methoxy-3-methylpyrimidin-4-one (70 mg, 0.158 mmol, 1 equiv) and N- methylcarbamoyl chloride (30 mg, 0.316 mmol, 2 equiv) in DCM were added TEA (44 µL, 0.316 mmol, 2 equiv) dropwise at ambient temperature. The mixture was concentrated under reduced pressure. The residue was purified by Prep-TLC (EA) to afford 1-{2-[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6- oxopyrimidin-2-yl]-3-cyclobutyl-1,3-benzodiazol-5-yl}-3-meth ylurea (40 mg, 51%) as a yellow solid. ES MS M/Z = 500.10 [M+H] ⁺ . [00637] Step 2: A mixture of 1-{2-[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxopyrimi din-2- yl]-3-cyclobutyl-1,3-benzodiazol-5-yl}-3-methylurea (35 mg, 0.070 mmol, 1 equiv) in DMF (1 mL) was added LiBr (30 mg, 0.350 mmol, 5 equiv). The mixture was stirred for 16 h at 100 °C. The crude product was purified by Prep-HPLC with the following conditions (Column: XSelect CSH Prep C18 OBD Column, 19*150 mm, 5 μm; Mobile Phase A: Water(0.1%FA), Mobile Phase B: acetonitrile: THF=1:1; Flow rate: 25 mL/min; Gradient: 17% B to 43% B in 10 min, 43% B; Wave Length: 254 nm; RT(min): 8.4; Injection Volume: 0.3 mL) to afford 1-{2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6- oxopyrimidin-2-yl]-3-cyclobutyl-1,3-benzodiazol-5-yl}-3-meth ylurea (2.7 mg, 8%). ES MS M/Z = 486.10 [M+H] ⁺ , UPLC: 95%; ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 8.75 (s, 1H), 8.27 (s, 1H), 7.93-7.78 (m, 2H), 7.62 (d, J = 8.7 Hz, 1H), 7.54 - 7.41 (m, 2H), 7.16 - 7.12 (m, 1H), 6.07 - 6.05 (m, 1H), 5.21 (t, J = 8.5 Hz, 1H), 3.55 (s, 3H), 2.72 - 2.65 (m, 5H), 2.35-2.31 (m, 2H), 1.85 - 1.82 (m, 2H). Example 142: 1-(2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6-d ihydropyrimidin-2-yl)- 1-cyclobutyl-1H-benzo[d]imidazol-6-yl)urea [00638] Step 1: A mixture of 2-(6-amino-1-cyclobutyl-1,3-benzodiazol-2-yl)-6-(1,3-benzoxa zol-2-yl)- 5-methoxy-3-methylpyrimidin-4-one (50 mg, 0.113 mmol, 1 equiv) and sodium cyanate (9 mg, 0.136 mmol, 1.2 equiv) in acetic acid (0.5 mL) and H2O (1 mL, 0.005 mmol, 0.5 equiv) was stirred for 2 h at 50 °C. The precipitated solids were collected by filtration and washed with water (3 x 3 mL) to afford the crude product 2-[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxopyrimidin -2-yl]-3-cyclobutyl-1,3- benzodiazol-5-ylurea (50 mg, 91.14%) as a yellow solid. ES MS M/Z = 486.10 [M+H] ⁺ . [00639] Step 2: A mixture of 2-[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxopyrimidin -2-yl]-3- cyclobutyl-1,3-benzodiazol-5-ylurea (35 mg, 0.072 mmol, 1 equiv) in DMF was added LiBr (31 mg, 0.360 mmol, 5 equiv). The mixture was stirred for 16 h at 100 °C. The crude product was purified by reversed-phase flash chromatography (column, C18 silica gel; mobile phase, acetonitrile in Water (0.05% HCOOH), 10% to 60% gradient in 20 min; detector, UV 254 nm) to afford 2-[4-(1,3-benzoxazol-2-yl)-5- hydroxy-1-methyl-6-oxopyrimidin-2-yl]-3-cyclobutyl-1,3-benzo diazol-5-ylurea (8.6 mg, 25.13%). ES MS M/Z = 472.10 [M+H] ⁺ , UPLC: 99%; ¹ H NMR (300 MHz, DMSO-d6) δ 11.47 (s, 1H), 8.77 (s, 1H), 8.21 (d, J = 1.9 Hz, 1H), 7.90 - 7.80 (m, 2H), 7.63 (d, J = 8.7 Hz, 1H), 7.55 -7.41 (m, 2H), 7.19 (d, J = 8.8 Hz, 1H), 5.90 (s, 2H), 5.26 - 5.14 (m, J = 8.7 Hz, 1H), 3.56 (s, 3H), 2.75-2.58 (m, 2H), 2.49 - 2.42 (m, 2H),1.92-1.73 (m, 2H). Example 143: 6-(1,3-benzoxazol-2-yl)-2-(1-cyclobutyl-4,5,6,7-tetrahydro-1 ,3-benzodiazol-2-yl)-5- hydroxy-3-methylpyrimidin-4-one [00640] Step 1: The mixture of 4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxopyrimidine-2 - carbaldehyde (100 mg, 0.351 mmol, 1 equiv) and cyclobutylamine (49 mg, 0.702 mmol, 2 equiv) in EtOH (5 mL) was stirred at 80°C for 30 min. The reaction worked according to TLC. To the mixture was added 1,2-cyclohexanedione (78.61 mg, 0.702 mmol, 2 equiv) and NH ₄ OAc (272 mg, 0.350 mmol, 5 equiv). The mixture was stirred at 80°C for 2h. The residue was purified by reversed-phase flash chromatography (column, C18 silica gel; mobile phase, acetonitrile in Water (0.05% TFA), 30% to 100% gradient in 30 min; detector, UV 254 nm) to afford 6-(1,3-benzoxazol-2-yl)-2-(1-cyclobutyl-4,5,6,7- tetrahydro-1,3-benzodiazol-2-yl)-5-methoxy-3-methylpyrimidin -4-one (40 mg, 26%) as brown oil. ES MS M/Z = 432.2 [M+H] ⁺ [00641] Step 2: To the mixture of 6-(1,3-benzoxazol-2-yl)-2-(1-cyclobutyl-4,5,6,7-tetrahydro-1 ,3- benzodiazol-2-yl)-5-methoxy-3-methylpyrimidin-4-one (100 mg, 0.232 mmol, 1 equiv) in DMF (3 mL) was added LiBr (120 mg, 1.392 mmol, 6 equiv). The mixture was stirred at 100°C for 4 h. The mixture was purified by reversed-phase flash chromatography (column, C18 silica gel; mobile phase, acetonitrile in water (0.05% FA), 10% to 50% gradient in 20 min; detector, UV 254 nm) The product was purified by trituration with acetonitrile (1 mL) to afford 6-(1,3-benzoxazol-2-yl)-2-(1-cyclobutyl-4,5,6,7-tetrahydro- 1,3-benzodiazol-2-yl)-5-hydroxy-3-methylpyrimidin-4-one (9.5 mg, 9%). ES MS M/Z = 418.1 [M+H] ⁺ , UPLC: 96%; ¹ H NMR (300 MHz, DMSO-d ₆ ) δ8.01 - 7.78 (m, 2H), 7.50 - 7.41 (m, 2H), 4.92 - 4.83 (m, 1H), 3.54 (s, 3H), 2.76 (s, 3H), 2.35 - 2.24 (m, 6H), 1.83 - 1.74 (m, 4H), 1.70 - 1.60 (m, 2H). Example 150: 2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyrimidin -2-yl]-N,N-dimethyl- 1-(1-methylimidazol-2-yl)-3,4-dihydro-1H-isoquinoline-7-carb oxamide [00642] Step 1: To a stirred solution of 7-bromo-3,4-dihydro-2H-isoquinolin-1-one (5 g, 22.117 mmol, 1 equiv) in THF (50 mL) was added TEA (6.71 g, 66.35 mmol, 3 equiv) at ambient temperature. To the mixture was added Boc2O (7.24 g, 33.18 mmol, 1.5 equiv) dropwise at 0 °C followed by DMAP (0.27 g, 2.21 mmol, 0.1 equiv) at ambient temperature. To the suspension, EtOAc (100 mL) and water (100 mL) were added. The aqueous phase was extracted with EtOAc (50 mL x 2). The combined organic phases were washed with brine (100 mL), dried with sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column to afford tert-butyl 7-bromo-1-oxo-3,4-dihydroisoquinoline-2-carboxylate (6.6 g, 86%) as a colorless solid. ES MS M/Z = 348.1 [M+Na] ⁺ . [00643] Step 2: n-BuLi (3.68 mL, 7.357 mmol, 1.2 equiv) was added dropwise into a colorless solution of 2-bromo-1-methylimidazole (0.99 g, 6.131 mmol, 1 equiv) in THF (85 mL) at -78 °C giving a yellow solution, which was stirred at this temperature for 1 h. Then, tert-butyl 7-bromo-1-oxo-3,4- dihydroisoquinoline-2-carboxylate (2 g, 6.131 mmol, 1 equiv) in THF (85 mL) was added dropwise. The obtained red solution was stirred at -78 °C for 2 h. The mixture was quenched by sat. aq. NH ₄ Cl (50 mL) and extracted by EtOAc (100 mL x 3). The organic layer was combined, washed by brine, dried over sodium sulfate, filtered, and concentrated to provide tert-butyl N-{2-[4-bromo-2-(1-methylimidazole-2- carbonyl)phenyl]ethyl}carbamate (2 g, 37%) as a yellow solid. ES MS M/Z = 408.1 [M+H] ⁺ . [00644] Step 3: NaBH ₄ (0.37 g, 9.8 mmol, 2 equiv) was added into a solution of tert-butyl N-{2-[4- bromo-2-(1-methylimidazole-2-carbonyl)phenyl]ethyl}carbamate (2 g, 4.9 mmol, 1 equiv) in MeOH (40 mL) at 0 °C giving a yellow suspension, which was allowed to warm to ambient temperature and stirred overnight. The reaction was quenched with water (50 mL). The mixture was extracted with CH(CH ₃ ) ₂ OH/CHCl ₃ (v/v, 1/3, 50 mL X 3). The combined organic phases were washed with brine (50 mL), dried with sodium sulfate, filtered, and concentrated. The obtained solid was submitted to silica gel column providing tert-butyl N-(2-{4-bromo-2-[hydroxy(1-methylimidazol-2- yl)methyl]phenyl}ethyl)carbamate (1.35 g, 65.7%) as a light yellow solid. ES MS M/Z = 410.0 [M+H] ⁺ . [00645] Step 4: A light brown solution of tert-butyl N-(2-{4-bromo-2-[hydroxy(1-methylimidazol-2- yl)methyl]phenyl}ethyl)carbamate (500 mg, 1.219 mmol, 1 equiv) in DCM (50 mL) and TFAA (0.25 mL) was stirred at ambient temperature for 1 h. The reaction was quenched with NaHCO3 (aq, 30 mL). The mixture was extracted with DCM (50 mL X 3). The combined organic phases were washed with brine (50 mL x 2), dried with sodium sulfate, filtered, and concentrated. The obtained oil was submitted to silica gel column giving tert-butyl 7-bromo-1-(1-methylimidazol-2-yl)-3,4-dihydro-1H-isoquinolin e-2- carboxylate (400 mg, 75.3%) as a light brown oil. ES MS M/Z = 392.1 [M+H] ⁺ . [00646] Step 5: A brown solution of tert-butyl 7-bromo-1-(1-methylimidazol-2-yl)-3,4-dihydro-1H- isoquinoline-2-carboxylate (400 mg, 1.020 mmol, 1 equiv) in DCM (2 mL) and TFA (2 mL) was stirred at ambient temperature for 1 h. The solvents were evaporated under 0 °C. The residue was diluted with CH(CH3)2OH/CHCl3 (v/v, 1/3, 10 mL), then adjusted to pH~8 with NH3.H2O. The mixture was extracted with CH(CH3)2OH/CHCl3 (v/v, 1/3, 10 mL x 3). The combined organic phases were washed with brine (20 mL), dried with sodium sulfate, filtered, and concentrated to provide 7-bromo-1-(1-methylimidazol- 2-yl)-1,2,3,4-tetrahydroisoquinoline (300 mg, 94%) as a light brown oil. ES MS M/Z = 292.1 [M+H] ⁺ . [00647] Step 6: A brown solution of 7-bromo-1-(1-methylimidazol-2-yl)-1,2,3,4- tetrahydroisoquinoline (290 mg, 0.993 mmol, 1 equiv), CsF (196 mg, 1.291 mmol, 1.3 equiv) in DMSO (3 mL) was stirred at 100 °C for 2 h. After cooling to ambient temperature, the reaction was diluted with EtOAc (20 mL) and water (10 mL). After separation of phases, the aqueous phase was extracted with EtOAc (10 mL x 2). The combined organic phases were washed with brine (20 mL), dried with sodium sulfate, filtered, and concentrated. The obtained residue was submitted to silica gel giving 6-(1,3- benzoxazol-2-yl)-2-[7-bromo-1-(1-methylimidazol-2-yl)-3,4-di hydro-1H-isoquinolin-2-yl]-5-methoxy-3- methylpyrimidin-4-one (500 mg, 65%) as a light brown solid. ES MS M/Z = 547.2 [M+H] ⁺ . [00648] Step 7: A dark brown solution of 6-(1,3-benzoxazol-2-yl)-2-[7-bromo-1-(1-methylimidazol-2- yl)-3,4-dihydro-1H-isoquinolin-2-yl]-5-methoxy-3-methylpyrim idin-4-one (300 mg, 0.548 mmol, 1 equiv) , Pd(OAc)2 (6 mg, 0.027 mmol, 0.05 equiv) , DMAP (134 mg, 1.096 mmol, 2 equiv) , dicobalt(2+) ion octakis(methanidylidyneoxidanium) (47 mg, 0.137 mmol, 0.25 equiv) and [5- (diphenylphosphanyl)-9,9-dimethyl-9H-xanthen-4-yl]diphenylph osphane (32 mg, 0.055 mmol, 0.1 equiv) in dimethylamine (2 M in THF) (15 mL) was stirred at 90 °C under N ₂ overnight. After cooled down to rt, EtOAc (50 mL) and water (50 mL) were added. The aqueous phase was extracted with EtOAc (50 mL x 2) and the combined organic phases were washed with brine (50 mL x 2), dried with sodium sulfate, filtered, and concentrated. The residue was submitted to silica gel column giving 2-[4- (1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxopyrimidin-2-yl ]-N,N-dimethyl-1-(1-methylimidazol-2- yl)-3,4-dihydro-1H-isoquinoline-7-carboxamide (140 mg, 42%) as a light brown solid. ES MS M/Z = 540.2 [M+H] ⁺ . [00649] Step 8: BBr3 (181 mg, 0.723 mmol, 3 equiv) was added dropwise into a solution of 2-[4-(1,3- benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxopyrimidin-2-yl]-N,N -dimethyl-1-(1-methylimidazol-2-yl)- 3,4-dihydro-1H-isoquinoline-7-carboxamide (130 mg, 0.241 mmol, 1 equiv) in DCM (2.6 mL) at 0 °C and the obtained solution was stirred at ambient temperature for 2 d. The reaction solution was diluted with ice water (5 mL) and the obtained mixture was extracted with DCM (10 mL x 3). The combined organic phases were washed with brine (15 mL), dried with sodium sulfate, filtered, and concentrated giving light brown solid (120 mg).40 mg of the solid was submitted to prep-HPLC (Column: XSelect CSH C18 Column, 19*250 mm, 5μm; Mobile Phase A: Water(0.1% FA), Mobile Phase B: acetonitrile; Flow rate: 25 mL/min mL/min; Gradient: 15% B to 45% B in7min; Wavelength: 254nm nm; RT(min): 6.33. After lyophilization, 2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyrimidin -2-yl]-N,N- dimethyl-1-(1-methylimidazol-2-yl)-3,4-dihydro-1H-isoquinoli ne-7-carboxamide (15.4 mg, 12%). ES MS M/Z = 526.2 [M+H] ⁺ , UPLC: 99.8%; ¹ H NMR (400 MHz, DMSO-d6) δ 10.59 (s, 1H), 7.89 - 7.81 (m, 2H), 7.53 - 7.42 (m, 2H), 7.31 - 7.20 (m, 2H), 7.07 (s, 1H), 6.82 (s, 1H), 6.68 (s, 1H), 6.13 (s, 1H), 3.89 - 3.78 (m, 4H), 3.56 (s, 3H), 3.42 - 3.36 (m, 1H), 3.19 - 3.06 (m, 1H), 3.03 - 2.96 (m, 1H), 2.95 - 2.80 (m, 6H). Chiral HPLC was used to provide the following compounds: Example 146: (R)-2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2- yl)-N,N-dimethyl-1-(1-methyl-1H-imidazol-2-yl)-1,2,3,4-tetra hydroisoquinoline-7-carboxamide [00650] ES MS M/Z = 526.2 [M+H] ⁺ , UPLC: 99.8%; ¹ H NMR (400 MHz, DMSO-d6) δ 10.59 (s, 1H), 7.89 - 7.81 (m, 2H), 7.53 - 7.42 (m, 2H), 7.31 - 7.20 (m, 2H), 7.07 (s, 1H), 6.82 (s, 1H), 6.68 (s, 1H), 6.13 (s, 1H), 3.89 - 3.78 (m, 4H), 3.56 (s, 3H), 3.42 - 3.36 (m, 1H), 3.19 - 3.06 (m, 1H), 3.03 - 2.96 (m, 1H), 2.95 - 2.80 (m, 6H). Stereochemistry arbitrarily assigned. Example 147: (S)-2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2- yl)-N,N-dimethyl-1-(1-methyl-1H-imidazol-2-yl)-1,2,3,4-tetra hydroisoquinoline-7-carboxamide [00651] ES MS M/Z = 526.2 [M+H] ⁺ , UPLC: 99.8%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.59 (s, 1H), 7.89 - 7.81 (m, 2H), 7.53 - 7.42 (m, 2H), 7.31 - 7.20 (m, 2H), 7.07 (s, 1H), 6.82 (s, 1H), 6.68 (s, 1H), 6.13 (s, 1H), 3.89 - 3.78 (m, 4H), 3.56 (s, 3H), 3.42 - 3.36 (m, 1H), 3.19 - 3.06 (m, 1H), 3.03 - 2.96 (m, 1H), 2.95 - 2.80 (m, 6H). Stereochemistry arbitrarily assigned. Example 148: (S)-2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2- yl)-N-(2-(dimethylamino)ethyl)-1-(2-fluorophenyl)-N-methyl-1 ,2,3,4-tetrahydroisoquinoline-7- carboxamide [00652] Step 1: To a stirred solution of [2-(dimethylamino)ethyl](methyl)amine (27 mg, 0.264 mmol, 1.5 equiv) in DMF (2.5 mL) was added DIEA (2491 mg, 0.704 mmol, 4 equiv), (1S)-2-[4-(1,3- benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyrimidin-2-yl]-1-( 2-fluorophenyl)-3,4-dihydro-1H- isoquinoline-7-carboxylic acid (90 mg, 0.176 mmol, 1 equiv) and HATU (100 mg, 0.264 mmol, 1.5 equiv). The mixture was stirred at ambient temperature for 3 h. The reaction progress was monitored by LCMS. After completion of the reaction, the crude product was purified by reverse-phase flash chromatography (Column: Xselect CSH C ₁₈ OBD Column, 30*150 mm, 5μm; Mobile Phase A: Water(0.05% TFA), Mobile Phase B: acetonitrile; Flow rate: 60 mL/min mL/min; Gradient: 30% B to 60% B in 7min; Wavelength: 254nm/220nm nm; RT(min): 8.1). After lyophilization, (S)-2-(4- (benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydropy rimidin-2-yl)-N-(2- (dimethylamino)ethyl)-1-(2-fluorophenyl)-N-methyl-1,2,3,4-te trahydroisoquinoline-7-carboxamide (21.1 mg, 19%). ES MS M/Z = 597.3 [M+H] ⁺ , UPLC: 96%; ¹ H NMR (400 MHz, DMSO-d6) δ 7.83 - 7.87 (m, 2H), 7.44 - 7.52 (m, 2H), 7.35 - 7.37 (m, 1H), 7.24 - 7.27 (m, 5H), 6.96 - 7.22 (m, 1H), 6.31 (m, 1H), 3.50 - 3.74 (m, 7H), 3.30 - 3.38 (m, 3H), 2.97 - 3.28 (m, 2H), 2.67 - 2.87 (m, 5H), 2.49 - 2.51 (m, 1H), 1.91 - 2.33(m, 2H). [00653] The following compounds were synthesized in a similar manner: Example 155: (R)-2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2- yl)-N-(2-(dimethylamino)ethyl)-1-(2-fluorophenyl)-N-methyl-1 ,2,3,4-tetrahydroisoquinoline-7- carboxamide ES MS M/Z = 597.3 [M+H] ⁺ , UPLC: 96%; ¹ H NMR (400 MHz, DMSO-d6) δ 7.83 - 7.87 (m, 2H), 7.44 - 7.52 (m, 2H), 7.35 - 7.37 (m, 1H), 7.24 - 7.27 (m, 5H), 6.96 - 7.22 (m, 1H), 6.31 (m, 1H), 3.50 - 3.74 (m, 7H), 3.30 - 3.38 (m, 3H), 2.97 - 3.28 (m, 2H), 2.67 - 2.87 (m, 5H), 2.49 - 2.51 (m, 1H), 1.91 - 2.33(m, 2H). Stereochemistry arbitrarily assigned. Example 157: (2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6-dih ydropyrimidin-2-yl)-N- (2-(dimethylamino)ethyl)-1-(2-fluorophenyl)-N-methyl-1,2,3,4 -tetrahydroisoquinoline-7- carboxamide ES MS M/Z = 597.3 [M+H] ⁺ , UPLC: 96%; ¹ H NMR (400 MHz, DMSO-d6) δ 7.83 - 7.87 (m, 2H), 7.44 - 7.52 (m, 2H), 7.35 - 7.37 (m, 1H), 7.24 - 7.27 (m, 5H), 6.96 - 7.22 (m, 1H), 6.31 (m, 1H), 3.50 - 3.74 (m, 7H), 3.30 - 3.38 (m, 3H), 2.97 - 3.28 (m, 2H), 2.67 - 2.87 (m, 5H), 2.49 - 2.51 (m, 1H), 1.91 - 2.33(m, 2H). Example 151: (1S)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyri midin-2-yl]-1-(2- fluorophenyl)-N-(2-hydroxyethyl)-N-methyl-3,4-dihydro-1H-iso quinoline-7-carboxamide [00654] To a stirred solution of methylethanolamine (20 mg, 0.264 mmol, 1.5 equiv) in anhydrous DMF (2.5 mL) was added DIEA (91 mg, 0.704 mmol, 4 equiv) at ambient temperature and stirred for 0.5 h. Then (1S)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyri midin-2-yl]-1-(2-fluorophenyl)- 3,4-dihydro-1H-isoquinoline-7-carboxylic acid (90 mg, 0.176 mmol, 1 equiv) and HATU (100.16 mg, 0.264 mmol, 1.5 equiv) were added to the reaction. The mixture was stirred for 3 h at ambient temperature. The reaction progress was monitored by LCMS. After completion of the reaction, the crude product was purified by reverse-phase flash chromatography (Column: Xselect CSH C ₁₈ OBD Column, 30*150 mm, 5μm; Mobile Phase A: Water (0.05% TFA), Mobile Phase B: acetonitrile; Flow rate: 60 mL/min mL/min; Gradient: 30% B to 60% B in 7min; Wavelength: 254nm/220nm nm; RT(min): 8.1). After lyophilization, (1S)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyri midin-2-yl]-1-(2- fluorophenyl)-N-(2-hydroxyethyl)-N-methyl-3,4-dihydro-1H-iso quinoline-7-carboxamide (16.8 mg, 16%) was afforded as a grey solid. ES MS M/Z = 570.3 [M+H] ⁺ , UPLC: 95%; ¹ H NMR (400 MHz, DMSO-d6) δ 10.59 (s, 1H), 7.86 - 7.87 (s, 2H), 7.45 - 7.52 (m, 2H), 7.03 - 7.27 (s, 6H), 6.09 (m, 1H), 6.31 (m, 1H), 3.51 - 3.75 (m, 4H), 3.18 - 3.43 (m, 6H), 2.91 - 3.01 (m, 4H), 1.23 (m, 1H). [00655] The following compound were synthesized in a similar manner: Example 156: (1R)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyri midin-2-yl]-1-(2- fluorophenyl)-N-(2-hydroxyethyl)-N-methyl-3,4-dihydro-1H-iso quinoline-7-carboxamide [00656] ES MS M/Z = 570.3 [M+H] ⁺ , UPLC: 95%; ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.59 (s, 1H), 7.86 - 7.87 (s, 2H), 7.45 - 7.52 (m, 2H), 7.03 - 7.27 (s, 6H), 6.09 (m, 1H), 6.31 (m, 1H), 3.51 - 3.75 (m, 4H), 3.18 - 3.43 (m, 6H), 2.91 - 3.01 (m, 4H), 1.23 (m, 1H). Stereochemistry arbitrarily assigned. Example 144: (1S)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyri midin-2-yl]-N-(2,3- dihydroxypropyl)-1-(2-fluorophenyl)-N-methyl-3,4-dihydro-1H- isoquinoline-7-carboxamide [00657] Step 1: A yellow solution of methyl (1S)-1-(2-fluorophenyl)-1,2,3,4-tetrahydroisoquinoline-7- carboxylate (500 mg, 1.752 mmol, 1 equiv), 6-(1,3-benzoxazol-2-yl)-2-chloro-5-methoxy-3- methylpyrimidin-4-one (767 mg, 2.628 mmol, 1.5 equiv) and CsF (346 mg, 2.278 mmol, 1.3 equiv) in DMSO (6 mL) was stirred at 100 ℃ for 4 h. After cooling to rt, EtOAc (20 mL) and H2O (20 mL) were added. To the mixture was added H2O (30 mL), the mixture was extracted with EtOAc (20 mL x 2). The combined organic phases were washed with brine (50 mL), dried with sodium sulfate, filtered, and concentrated to afford methyl (1S)-2-[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxopyri midin-2- yl]-1-(2-fluorophenyl)-3,4-dihydro-1H-isoquinoline-7-carboxy late (800 mg, 79%). ES MS M/Z = 541.20 [M+H] ⁺ . [00658] Step 2: A yellow solution of methyl (1R)-2-[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6- oxopyrimidin-2-yl]-1-(2-fluorophenyl)-3,4-dihydro-1H-isoquin oline-7-carboxylate (800 mg, 1.48 mmol, 1 equiv), LiBr (643 mg, 7.40 mmol, 5 equiv) in DMF (9 mL). The mixture was stirred at 100 ℃ for 16 h. To the mixture was added H2O (30 mL), the mixture was extracted was extracted with EtOAc (20 mL x 2). The combined organic phases were washed with brine (20 mL), dried with sodium sulfate, filtered, and concentrated. The residue was submitted to silica gel column giving methyl (1S)-2-[4-(1,3- benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyrimidin-2-yl]-1-( 2-fluorophenyl)-3,4-dihydro-1H- isoquinoline-7-carboxylate (720 mg, 92%). ES MS M/Z = 527.20 [M+H] ⁺ . [00659] Step 3: To a stirred solution of methyl (1R)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6- oxopyrimidin-2-yl]-1-(2-fluorophenyl)-3,4-dihydro-1H-isoquin oline-7-carboxylate (230 mg, 0.437 mmol, 1 equiv) in THF (9 mL) and MeOH (3 mL) were added LiOH (32 mg, 1.311 mmol, 3 equiv) in H2O (3 mL) at ambient temperature. The mixture was stirred for 16 h then acidified to pH 5 with 2M HCl. The solid was collected by filtration which provided (1R)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1- methyl-6-oxopyrimidin-2-yl]-1-(2-fluorophenyl)-3,4-dihydro-1 H-isoquinoline-7-carboxylic acid (170 mg, 76%) as a yellow solid. ES MS M/Z = 513.15 [M+H] ⁺ . [00660] Step 4: To a stirred solution of (1S)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6- oxopyrimidin-2-yl]-1-(2-fluorophenyl)-3,4-dihydro-1H-isoquin oline-7-carboxylic acid (70 mg, 0.137 mmol, 1 equiv), 3-(methylamino)propane-1,1-diol (28.72 mg, 0.274 mmol, 2 equiv) and DIEA (70.61 mg, 0.548 mmol, 4 equiv) in DMF (2 mL) was added HATU (77.90 mg, 0.206 mmol, 1.5 equiv). The resulting mixture was stirred for additional 1 h at ambient temperature. The residue was purified by reversed-phase flash chromatography (column: Xselect CSH C18 OBD Column, 30*150 mm, 5μm; Mobile Phase A: Water(0.1% FA), Mobile Phase B: acetonitrile; Flow rate: 60 mL/min mL/min; Gradient: 27% B to 57% B in 7min; Wavelength: 254nm/220nm nm; RT(min): 5.83 to afford (1S)-2-[4- (1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyrimidin-2-yl ]-N-(2,3-dihydroxypropyl)-1-(2- fluorophenyl)-N-methyl-3,4-dihydro-1H-isoquinoline-7-carboxa mide (22.4 mg, 27%). ES MS M/Z =600.25 [M+H] ⁺ , UPLC: 99.7%; ¹ H NMR (300 MHz, DMSO-d6) δ 7.93 – 7.81 (m, 2 H), 7.62 – 7.41 (m, 2 H), 7.41 – 6.96 (m, 6 H), 6.96 – 6.83 (m, 1 H), 6.38 – 6.19 (m, 1 H), 3.85 – 3.71 (m, 1 H), 3.70 – 3.45 (m, 5 H), 3.36 – 3.02 (m, 6 H), 2.98 – 2.85 (m, 3 H) [00661] The following compounds were synthesized in a similar manner: Example 164: (1R)-2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6 -dihydropyrimidin-2- yl)-N-(2,3-dihydroxypropyl)-1-(2-fluorophenyl)-N-methyl-1,2, 3,4-tetrahydroisoquinoline-7- carboxamide ES MS M/Z = 600.30 [M+H] ⁺ ; UPLC: 99.34%; ¹ H NMR (300 MHz, DMSO-d6) δ 8.01 – 7.81 (m, 2H), 7.63 – 7.42 (m, 2H), 7.40 – 6.96 (m, 6H), 7.03 – 6.03 (m, 1H), 4.85 – 4.55 (m, 6H), 3.39 – 3.21 (m, 4H), 3.23 – 3.09 (m, 1H), 3.02 – 2.98 (m, 1H), 3.09 – 2.98 (m, 3H). Stereochemistry arbitrarily assigned. Example 145: (1S)-2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6 -dihydropyrimidin-2- yl)-1-(2-fluorophenyl)-N-methyl-N-(2-(((2R,5R,6R)-3,4,5-trih ydroxy-6-(hydroxymethyl)tetrahydro- 2H-pyran-2-yl)oxy)ethyl)-1,2,3,4-tetrahydroisoquinoline-7-ca rboxamide [00662] ES MS M/Z = 732.25 [M+H] ⁺ ; ¹ H NMR (300 MHz, DMSO-d6) δ 7.88 – 7.86 (m, 2 H), 7.53 – 6.85 (m, 10 H), 6.32 – 6.30 (m, 1 H), 3.69 – 2.87 (14 H), 3.10 – 2.51 (11 H). Stereochemistry arbitrarily assigned. Example 165: (1S)-2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6 -dihydropyrimidin-2- yl)-1-(2-fluorophenyl)-N-methyl-N-(2-(((2R,5R,6R)-3,4,5-trih ydroxy-6-(hydroxymethyl)tetrahydro- 2H-pyran-2-yl)oxy)ethyl)-1,2,3,4-tetrahydroisoquinoline-7-ca rboxamide [00663] ES MS M/Z = 732.25 [M+H] ⁺ ; ¹ H NMR (300 MHz, DMSO-d6) δ 7.88 – 7.86 (m, 2 H), 7.53 – 6.85 (m, 10 H), 6.32 – 6.30 (m, 1 H), 3.69 – 2.87 (14 H), 3.10 – 2.51 (11 H). Stereochemistry arbitrarily assigned. Example 149: 2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6-dihy dropyrimidin-2-yl)- N,N-dimethyl-1-(pyridin-4-yl)-1,2,3,4-tetrahydroisoquinoline -7-carboxamide

[00664] Step 1: To a solution of tert-butyl 7-bromo-3,4-dihydro-1H-isoquinoline-2-carboxylate (12 g, ^{38.4 mmol, 1 equiv) in MeOH (150 mL) was added Pd(dppf)Cl} 2 ^{(2.81 g, 3.84 mmol, 0.1 equiv) and Et} 3 ^N (15.6 g, 153.7 mmol, 4 equiv) in a pressure tank. The mixture was pressurized to 20 atm with carbon monoxide at 130 °C overnight. The reaction mixture was cooled to ambient temperature and filtered to remove insoluble solids. The resulting mixture was concentrated under reduced pressure then purified by silica gel column chromatography, eluted with PE / EA (5:1) to afford 2-tert-butyl 7-methyl 3,4-dihydro- 1H-isoquinoline-2,7-dicarboxylate (10.22 g, 91%) as a colorless solid. ES MS M/Z = 236.1 [M-tBu+H] ⁺ . [00665] Step 2: A solution of 2-tert-butyl 7-methyl 3,4-dihydro-1H-isoquinoline-2,7-dicarboxylate (2 g, 3.4 mmol, 1 equiv) in DMA (32 mL) was treated with 4-cyanopyridine (0.72 g, 3.43 mmol, 1 equiv), K ₂ HPO ₄ (0.60 g, 3.43 mmol, 1 equiv), triphenylsilanethiol (100 mg, 0.172 mmol, 0.05 equiv) and tris(2- phenylpyridine) iridium (40 mg, 0.034 mmol, 0.01 equiv) for 2 h at room temperature under nitrogen atmosphere under light (LED). The reaction was quenched by the addition of water (50mL) at ambient temperature. The resulting mixture was extracted with EtOAc (3 x 40mL). The combined organic layers were washed with water (2 x 50 mL) and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford 2-tert-butyl 7-methyl 1-(pyridin-4-yl)-3,4-dihydro-1H-isoquinoline- 2,7-dicarboxylate (1.36 g, 54%) as a yellow solid. ES MS M/Z = 369.2 [M-tBu+H] ⁺ . [00666] Step 3: A solution of 2-tert-butyl 7-methyl 1-(pyridin-4-yl)-3,4-dihydro-1H-isoquinoline-2,7- dicarboxylate (1 g, 2.790 mmol, 1 equiv) in THF (15 mL), MeOH (4 mL) and H2O (4 mL) was treated with LiOH (0.40 g, 16.740 mmol, 6 equiv) for 2 h at room temperature. Desired product could be detected by LCMS. The reaction was quenched by the addition of water (10mL) at ambient temperature. The resulting mixture was concentrated under reduced pressure. The mixture was acidified to pH 6 with 2M HCl. The precipitated solids were collected by filtration and dissolved in CHCl3:IPA (3:1). The resulting liquid was dried by MgSO4, filtered, and concentrated under reduced pressure to afford 2-(tert- butoxycarbonyl)-1-(pyridin-4-yl)-3,4-dihydro-1H-isoquinoline -7-carboxylic acid (790 mg, 80%) as a colorless solid. ES MS M/Z = 355.1 [M-tBu+H] ⁺ . [00667] Step 4: A solution of 2-(tert-butoxycarbonyl)-1-(pyridin-4-yl)-3,4-dihydro-1H-isoq uinoline-7- carboxylic acid (790 mg, 2.23 mmol, 1 equiv) in DMF (15 mL) was treated with dimethylamine (120 mg, 2.68 mmol, 1.2 equiv), DIEA (864 mg, 6.69 mmol, 3 equiv) and HATU (1271 mg, 3.344 mmol, 1.5 equiv) for 2 h at ambient temperature. The reaction was quenched with water at ambient temperature. The aqueous layer was extracted with EtOAc (3 x 40mL). The resulting mixture was washed with H2O (2 x 100 mL) and brine (100 mL) then dried with anhydrous sodium sulfate. The resulting mixture was concentrated under reduced pressure and purified by reversed-phase flash chromatography (column, C18 silica gel; mobile phase, acetonitrile in Water (10mmol/L NH4HCO3), 10% to 50% gradient in 10 min; detector, UV 254 nm) to afford tert-butyl 7-(dimethylcarbamoyl)-1-(pyridin-4-yl)-3,4-dihydro-1H- isoquinoline-2-carboxylate) (700 mg, 82%) as a colorless solid. ES MS M/Z = 382.2 [M+H] ⁺ _. [00668] Step 5: A solution of tert-butyl 7-(dimethylcarbamoyl)-1-phenyl-3,4-dihydro-1H-isoquinoline- 2-carboxylate (700 mg, 1.84 mmol, 1 equiv) in DCM (10 mL) was treated with TFA (2 mL) for 30 min at ambient temperature. The resulting mixture was concentrated under reduced pressure then dissolved in DCM (30 mL). The mixture was neutralized to pH 7 with saturated NaHCO3 (aq.). The aqueous layer was extracted with DCM (2 x 30 mL). The resulting mixture was washed with brine (80 mL) then dried with MgSO4, filtered, and concentrated under reduced pressure to afford N,N-dimethyl-1-phenyl-1,2,3,4- tetrahydroisoquinoline-7-carboxamide (300 mg, 58%) as a colorless solid. ES MS M/Z = 382.2 [M+H] ⁺ . [00669] Step 6: To the mixture of N,N-dimethyl-1-(pyridin-4-yl)-1,2,3,4-tetrahydroisoquinoline -7- carboxamide (100 mg, 0.355 mmol, 1 equiv) and 6-(1,3-benzoxazol-2-yl)-2-chloro-5-methoxy-3- methylpyrimidin-4-one (135 mg, 0.461 mmol, 1.3 equiv) in DMSO (3 mL) was added CsF (70 mg, 0.461 mmol, 1.3 equiv) . The mixture was stirred at 80 °C for 4 h under N2 atmosphere. The mixture was purified by reversed-phase flash chromatography (column, C18 silica gel; mobile phase, acetonitrile in water (0.1% FA), 20% to 60% gradient in 30 min; detector, UV 254 nm) to afford 2-[4-(1,3-benzoxazol- 2-yl)-5-methoxy-1-methyl-6-oxopyrimidin-2-yl]-N,N-dimethyl-1 -(pyridin-4-yl)-3,4-dihydro-1H- isoquinoline-7-carboxamide (100 mg, 52%) as yellow solid. ES MS M/Z = 537.3 [M+H] ⁺ . [00670] Step 7: To the mixture of 2-[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxopyrimidin -2- yl]-N,N-dimethyl-1-(pyridin-4-yl)-3,4-dihydro-1H-isoquinolin e-7-carboxamide (80 mg, 0.149 mmol, 1 equiv) in DCM (2 mL) was added BBr ₃ (0.89 mL, 0.894 mmol, 6 equiv) at -78 °C under nitrogen atmosphere. The mixture was stirred at ambient temperature for 2 h. The mixture was quenched with MeOH (3 mL) then concentrated. The residue was purified by reversed-phase flash chromatography (column, C18 silica gel; mobile phase, acetonitrile in water (0.1% FA), 20% to 60% gradient in 10 min; detector, UV 254 nm) to afford 2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyrimidin -2-yl]- N,N-dimethyl-1-(pyridin-4-yl)-3,4-dihydro-1H-isoquinoline-7- carboxamide (6.3 mg, 8%). ES MS M/Z = 523.3 [M+H] ⁺ , UPLC: 97%; ¹ H NMR (400 MHz, DMSO-d6) δ 8.38 (s, 2H), 8.31 (s, 1H), 8.08 (s, 1H), 7.85 (s, 1H), 7.43 – 7.33 (m, 4H), 7.25 (d, J = 7.9 Hz, 1H), 6.83 (s, 1H), 6.01 (s, 1H), 3.61 - 3.56 (m, 4H), 3.17 - 3.00 (m, 2H), 2.98 - 2.89 (m, 1H), 2.92 – 2.87 (m, 3H), 2.77 (d, J = 8.3 Hz, 3H). Example 154: 2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6-dihy dropyrimidin-2-yl)- N,N-dimethyl-1-(pyridin-3-yl)-1,2,3,4-tetrahydroisoquinoline -7-carboxamide [00671] Step 1: To a stirred solution of methyl 1-(methylsulfanyl)-3,4-dihydroisoquinoline-7- carboxylate (500 mg, 2.13 mmol, 1 equiv) in anhydrous THF (10 mL) was added CuTc (486 mg, 2.55 mmol, 1.2 equiv) followed by Pd(PPh3)4 (246 mg, 0.213 mmol, 0.1 equiv) at ambient temperature. The reaction mixture was stirred at 80 °C for 16 h. The reaction mixture was quenched by addition of water (10 mL) then extracted with ethyl acetate (3 x 10 mL). The combined organic phases were washed with brine (20 mL), dried over anhydrous sodium sulfate, and concentrated. The crude product was further purified by column chromatography using 5% to 30% EA in PE gradient to afford methyl 1-(pyridin-3- yl)-3,4-dihydroisoquinoline-7-carboxylate (300 mg, 53%). ES MS M/Z = 267.25 [M+H] ⁺ . [00672] Step 2: A brown solution of methyl 1-(pyridin-3-yl)-3,4-dihydroisoquinoline-7-carboxylate (90 mg, 0.338 mmol, 1 equiv) in MeOH (5 mL) was added NaBH4 (64 mg, 1.69 mmol, 5 equiv). The mixture was stirred at 0 °C for 1 h. The mixture was then quenched with NH4Cl (aq.10 mL) and extracted with EA (3 x 20 mL). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated to provide methyl 1-(pyridin-3-yl)-1,2,3,4- tetrahydroisoquinoline-7-carboxylate (60 mg, 66%) as a yellow solid. ES MS M/Z = 269.15 [M+H] ⁺ . The crude product was used in the next step directly without further purification. [00673] Step 3: A solution of methyl 1-(pyridin-3-yl)-1,2,3,4-tetrahydroisoquinoline-7-carboxylat e (90 mg, 0.335 mmol, 1 equiv), 6-(1,3-benzoxazol-2-yl)-2-chloro-5-methoxy-3-methylpyrimidin -4-one (127 mg, 0.436 mmol, 1.3 equiv), CsF (56 mg, 0.369 mmol, 1.1 equiv) in DMSO (2 mL) was stirred at 80 ℃ overnight. The reaction mixture was quenched with water (10 mL) and extracted with ethyl acetate (3 x 20 mL). The combined organic layers were washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to afford methyl 2-[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6- oxopyrimidin-2-yl]-1-(pyridin-3-yl)-3,4-dihydro-1H-isoquinol ine-7-carboxylate (60 mg, 34%) as a yellow solid. ES MS M/Z = 524.15 [M+H] ⁺ . The crude product was used in the next step directly without further purification. [00674] Step 4: To a solution of methyl 2-[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6- oxopyrimidin-2-yl]-1-(pyridin-3-yl)-3,4-dihydro-1H-isoquinol ine-7-carboxylate (60 mg, 0.11 mmol) and lithium hydroxide (8 mg, 0.34 mmol) in water (1 mL) was added giving a brown suspension. The mixture was stirred overnight at ambient temperature. The resulting mixture was diluted with water (20 mL) washed with DCM (3 x 30 mL). The aqueous layer was acidified to pH = 2 with HCl (aq.2.0 M). The precipitated solids were collected by filtration and washed with DCM (3 x 30 mL) to afford 2-(4- (benzo[d]oxazol-2-yl)-5-methoxy-1-methyl-6-oxo-1,6-dihydropy rimidin-2-yl)-N,N-dimethyl-1-(pyridin- 3-yl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide(50 mg, 86%) as a yellow solid. ES MS M/Z = 510.15 [M+H] ⁺ . [00675] Step 5: A brown solution of 2-(4-(benzo[d]oxazol-2-yl)-5-methoxy-1-methyl-6-oxo-1,6- dihydropyrimidin-2-yl)-1-(pyridin-3-yl)-1,2,3,4-tetrahydrois oquinoline-7-carboxylic acid (50 mg, 0.098 mmol), dimethylamine (9 mg, 0.196mmol), HATU (56 mg, 0.147 mmol) and DIEA (38 mg, 0.294 mmol) in DMF (1 mL) was stirred at ambient temperature for 5 h. The reaction solution was diluted with water (5 mL) and the obtained mixture was extracted with CH(CH3)2OH/CHCl3 (v/v, 1/3, 10 mL X 3). The combined organic phases were washed with brine (10 mL), dried with sodium sulfate, filtered, and concentrated. The residue was purified by reversed-phase flash chromatography (column, C18 silica gel; mobile phase, acetonitrile in Water (0.1% FA), 10% to 50% gradient in 10 min; detector, UV 254 nm) to afford 2-(4-(benzo[d]oxazol-2-yl)-5-methoxy-1-methyl-6-oxo-1,6-dihy dropyrimidin-2-yl)-N,N-dimethyl- 1-(pyridin-3-yl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamid e as a green solid (50 mg). ES MS M/Z = 537.15 [M+H] ⁺ . [00676] Step 6: A solution/mixture of 2-[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6- oxopyrimidin-2-yl]-N,N-dimethyl-1-(pyridin-3-yl)-3,4-dihydro -1H-isoquinoline-7-carboxamide (50 mg, 0.093 mmol, 1 equiv) and lithium bromide (81 mg, 0.930 mmol, 10 equiv) in DMF (1 mL) was stirred for overnight at 100 °C. The mixture was allowed to cool to ambient temperature. The resulting mixture was diluted with water (10 mL) then extracted with EtOAc (3 x 10 mL). The combined organic layers were washed with brine (1 x 20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product (30 mg) was purified by Prep-HPLC (Column: XSelect CSH C ₁₈ Column, 19*250 mm, 5 μm; Mobile Phase A: Water(0.1% FA), Mobile Phase B: acetonitrile; Flow rate: 25 mL/min; Gradient: 15% B to 40% B in10 min; Wave Length: 254nm; RT(min): 9.58) to afford 2-[4-(1,3-benzoxazol-2-yl)- 5-hydroxy-1-methyl-6-oxopyrimidin-2-yl]-N,N-dimethyl-1-(pyri din-3-yl)-3,4-dihydro-1H-isoquinoline- 7-carboxamide; formic acid (2.4 mg, 5%). ES MS M/Z = 523.25 [M+H] ⁺ , UPLC: 96.76%; ¹ H NMR (400 MHz, DMSO-d6) δ 8.57 (s, 1H), 8.31 (s, 1H), 8.18 (s, 1H), 7.87 (s, 2H), 7.67 (s, 1H), 7.49 (s, 3H), 7.35 (s, 1H), 7.24 (s, 2H), 6.82 (s, 1H), 6.09 (s, 1H), 3.55 (s, 3H), 3.36 (s, 2H), 2.88 (s, 3H), 2.74 (d, J = 9.3 Hz, 3H), 1.20 (s, 1H). Example 158: (R)-2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-6-oxo-1,6-dihydropy rimidin-2-yl)-N,N- dimethyl-1-phenyl-1,2,3,4-tetrahydroisoquinoline-7-carboxami de [00677] Steps 1,2: MeONa (5.70 g, 31.65 mmol, 1.5 equiv, 30%w/w in MeOH) was added dropwise into a solution of methyl 2,6-dichloro-5-methoxypyrimidine-4-carboxylate (5 g, 21.09 mmol, 1 equiv) in MeOH (30 mL) at 0 °C and the light yellow solution was stirred at 0 °C for 1 h to provide methyl 2- chloro-5,6-dimethoxypyrimidine-4-carboxylate in MeOH. The solution was used without purification. THF (90 mL) was added, follow by a solution of LiOH (1.52 g, 63.466 mmol, 3.01 equiv) in H2O (30 mL). The resulting reaction was stirred at ambient temperature overnight. The resulting mixture was concentrated under vacuum to remove the majority of solvent. Lypholization provided 2-chloro-5,6- dimethoxypyrimidine-4-carboxylic acid (6 g, 117%, crude) as a colorless solid. ES MS M/Z = 219.0 [M+H] ⁺ . [00678] Step 3: T3P (19.94 g, 62.68 mmol, 5 equiv) was added dropwise into a solution of 2-chloro- 5,6-dimethoxypyrimidine-4-carboxylic acid (2.74 g, 12.54 mmol, 1 equiv), 2-iodoaniline (3.29 g, 15.04 mmol, 1.2 equiv) in DCM (60 mL) at 0 °C. Then, DIEA (8.10 g, 62.68 mmol, 5 equiv) was added slowly at 0 °C. The obtained solution was stirred at ambient temperature for 4 h. The resulting mixture was concentrated under reduced pressure and purified by flash chromatography to provide 2-chloro-N-(2- iodophenyl)-5,6-dimethoxypyrimidine-4-carboxamide (1.5 g, 23%) as a colorless solid. ES MS M/Z = 420.0 [M+H] ⁺ . [00679] Step 4: Into a 40 mL vial 1 of 1,10-phenanthroline (129 mg, 0.715 mmol, 0.2 equiv) and CuCN (64 mg, 0.715 mmol, 0.2 equiv) was added DMF (12 mL) at ambient temperature under N ₂ . The resulting mixture was stirred at ambient temperature for 5 min. Into a 40 mL vial 2 of 2-chloro-N-(2- iodophenyl)-5,6-dimethoxypyrimidine-4-carboxamide (1.5 g, 3.575 mmol, 1 equiv) and Cs2CO3 (2.33 g, 7.150 mmol, 2 equiv) was added DMF (18 mL) at ambient temperature under N2. The resulting mixture was stirred at rt for 3 min. To a stirred solution of 40 ml vial 2 was added a stirred solution of 40 ml vial 1 at rt under N2. The resulting mixture was stirred at 100 °C overnight. The resulting mixture was extracted with DCM (1 x 30mL) and H2O (15 mL). The aqueous layer was extracted with DCM (2 x 30 mL) then submitted to reverse phase HPLC (0.05% TFA) providing 6-(1,3-benzoxazol-2-yl)-2-chloro-5- methoxypyrimidin-4-ol (130 mg, 12%) as a colorless solid. ES MS M/Z = 278.1 [M+H] ⁺ . [00680] Step 5: A brown solution of 6-(1,3-benzoxazol-2-yl)-2-chloro-5-methoxypyrimidin-4-ol (90 mg, 0.32 mmol, 1 equiv), (1R)-N,N-dimethyl-1-phenyl-1,2,3,4-tetrahydroisoquinoline-7- carboxamide (136 mg, 0.486 mmol, 1.5 equiv), Pd-PEPPSI-IHeptCl 3-chloropyridine (32 mg, 0.032 mmol, 0.1 equiv) and sodium trimethylsilanolate (73 mg, 0.65 mmol, 2 equiv) in 1,4-dioxane (1.2 mL) was stirred at 90 °C under N ₂ overnight. After cooling to rt, CHCl ₃ /CH(CH ₃ ) ₂ OH (v/v, 3/1, 10 mL) and water (10 mL) were added. After separation of the biphasic solution, the aqueous phase was extracted with CHCl3/CH(CH3)2OH (v/v, 3/1, 10 mL x 2). The combined organic phases were washed with brine (10 mL x 2), dried with Na ₂ SO ₄ , filtered and concentrated. The residue was purified by flash chromatography providing (1R)-2-[4-(1,3-benzoxazol-2-yl)-6-hydroxy-5-methoxypyrimidin -2-yl]-N,N-dimethyl-1- phenyl-3,4-dihydro-1H-isoquinoline-7-carboxamide (80 mg, 45%) as a yellow solid. ES MS M/Z = 522.3 [M+H] ⁺ . [00681] Step 6: To a stirred solution of (1R)-2-[4-(1,3-benzoxazol-2-yl)-6-hydroxy-5- methoxypyrimidin-2-yl]-N,N-dimethyl-1-phenyl-3,4-dihydro-1H- isoquinoline-7-carboxamide (70 mg, 0.134 mmol, 1 equiv) in DMF (1 mL) was added LiBr (58 mg, 0.67 mmol, 5 equiv) in portions at ambient temperature. The resulting mixture was stirred at 100 °C for overnight. The mixture was purified by HPLC to provide (1R)-2-[4-(1,3-benzoxazol-2-yl)-5-hydroxy-6-oxo-1H-pyrimidin -2-yl]-N,N- dimethyl-1-phenyl-3,4-dihydro-1H-isoquinoline-7-carboxamide (8.3 mg, 12%). ES MS M/Z = 508.2 [M+H] ⁺ , UPLC: 96%; ¹ H NMR (300 MHz, DMSO-d6) δ 12.06 (s, 1H), 10.16 (s, 1H), 7.94 - 7.84 (m, 2H), 7.56 - 7.43 (m, 2H), 7.40 - 7.21 (m, 7H), 7.17 (s, 1H), 6.89 (s, 1H), 4.27 - 4.12 (m, 1H), 3.53 - 3.40 (m, 1H), 3.12 - 3.00 (m, 1H), 2.99 – 2.81 (m, 7H). Example 159: 1-(2-(4-(benzo[d]oxazol-2-yl)-5-hydroxy-1-methyl-6-oxo-1,6-d ihydropyrimidin-2-yl)- 1-phenyl-1,2,3,4-tetrahydroisoquinolin-7-yl)urea

[00682] Step 1: A solution of 6-(1,3-benzoxazol-2-yl)-2-(7-bromo-1-phenyl-3,4-dihydro-1H- isoquinolin-2-yl)-5-methoxy-3-methylpyrimidin-4-one (1.447 g, 2.663 mmol, 1 equiv) in DMSO (10 mL) was treated with L-proline (0.12 g, 1.07 mmol, 0.4 equiv) K ₂ CO ₃ (1.10 g, 7.99 mmol, 3 equiv), NH3 ^. H2O (2.5 mL, 16.1 mmol, 6.03 equiv, 25%). The mixture was stirred for 10 h at 100 °C. The resulting mixture was filtered and the filter cake was washed with ethyl acetate (2 x 10 mL). The filtrate was concentrated under reduced pressure. The resulting mixture was extracted with EtOAc (3 x 10 mL). The combined organic layers were washed with H2O (3 x 10 mL), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by silica gel column chromatography, eluted with PE/EA (1:1) to afford 2-(7-amino-1-phenyl-3,4-dihydro-1H-isoquinolin-2- yl)-6-(1,3-benzoxazol-2-yl)-5-methoxy-3-methylpyrimidin-4-on e (750 mg, 59%) as an off-white solid. ES MS M/Z = 480.2 [M+H] ⁺ . [00683] Step 2: A solution of 2-(7-amino-1-phenyl-3,4-dihydro-1H-isoquinolin-2-yl)-6-(1,3- benzoxazol-2-yl)-5-methoxy-3-methylpyrimidin-4-one (750 mg, 1.56 mmol, 1 equiv) in H2O (5 mL) was treated with CH ₃ COOH (0.32 mL, 1.56 mmol, 1 equiv, 28%). The mixture was stirred for 20 h at 50 °C. The resulting mixture was filtered and the filter cake was washed with EtOAc (3 x 5 mL). The filtrate was concentrated under reduced pressure and the residue was purified by reversed-phase flash chromatography (column, C18 silica gel; mobile phase, acetonitrile in Water (0.05% NH4HCO3), 0% to 50% gradient in 20 min; detector, UV 254 nm) to afford 2-[4-(1,3-benzoxazol-2-yl)-5-methoxy-1- methyl-6-oxopyrimidin-2-yl]-1-phenyl-3,4-dihydro-1H-isoquino lin-7-ylurea (200 mg, 25%) as a brown solid. ES MS M/Z = 523.2 [M+H] ⁺ . [00684] Step 3: A solution of 2-[4-(1,3-benzoxazol-2-yl)-5-methoxy-1-methyl-6-oxopyrimidin -2-yl]-1- phenyl-3,4-dihydro-1H-isoquinolin-7-ylurea (200 mg, 0.383 mmol, 1 equiv) in DMF (5 mL) was added LiBr (400 mg, 4.596 mmol, 12 equiv). The mixture was stirred for 20 h at 100 °C. The residue was purified by reversed-phase flash chromatography (column, C18 silica gel; mobile phase, 0.05% aqueous formic acid in acetonitrile, 0% to 60% gradient in 30 min; detector, UV 254 nm) to afford 2-[4-(1,3- benzoxazol-2-yl)-5-hydroxy-1-methyl-6-oxopyrimidin-2-yl]-1-p henyl-3,4-dihydro-1H-isoquinolin-7- ylurea (15.5 mg, 8%). ES MS M/Z = 509.2 [M+H] ⁺ , UPLC: 97%; ¹ H NMR (400 MHz, DMSO-d6) δ 8.36 (s, 1 H), 7.86 - 7.94 (m, 2 H), 7.46 - 7.50 (m, 2 H), 7.29 - 7.32 (m, 1 H), 7.21 -7.26 (m, 4 H), 7.09 – 7.19 (m, 2 H), 6.81 - 6.82 (d, 1 H), 5.93 (s, 1 H), 5.69 (s, 2H), 3.51 -3.54 (d, 4 H), 3.17 – 3.32 (m, 2 H), 2.88 (s, 1 H). Example A. Human TREX1 Enzymatic Assay with dsDNA Native Oligonucleotide [00685] Human TREX1 enzyme (amino acids 1-242) was diluted in assay buffer (20 mM Tris pH 7.7, 5 mM MgCl ₂ , 0.01% human serum albumin, 0.01% Brij™-35, 2 mM dithiothreitol) to 0.3 nM and 5 µL was added to a 384-well low-binding polypropylene plate (final enzyme concentration in reaction is 0.15 nM) . Test compounds were prepared at 1 mM in DMSO (final DMSO concentration in reaction mixture of 0.3%) and serially diluted 3-fold into 10 stock concentrations.30 nL of each stock concentration was added to the wells with a concentration ranging from 3 µM to 0.15 nM. The reaction mixtures were incubated for 15 minutes at 24 °C and 5 µL of a solution of annealed dsDNA oligonucleotide was added to a final concentration of 50 nM. The reaction mixtures were incubated at 24 °C for 15 minutes and subsequently quenched by transferring part of the assay reaction to a solution of 100 mM ethylenediaminetetraacetic acid and 0.67% v/v Picogreen™ in a black plate with an opaque bottom. The fluorescence (emission wavelength 480 nm / excitation wavelength 520 nm) was measured using a Molecular Devices SpectraMax plate reader. Wells containing oligonucleotide but no TREX1 enzyme were used as negative controls. Wells containing oligonucleotide, TREX1 enzyme, and DMSO were used as positive controls. Example B. Murine TREX1 Enzymatic Assay with dsDNA Native Oligonucleotide [00686] Murine TREX1 enzyme (amino acids 1-242) was diluted in assay buffer (20 mM Tris pH 7.7, 5 mM MgCl ₂ , 0.01% human serum albumin, 0.01% Brij™-35, 2 mM dithiothreitol) to 0.3 nM and 5 µL was added to a 384-well low-binding polypropylene plate (final enzyme concentration in reaction is 0.15 nM) . Test compounds were prepared at 1 mM in DMSO (final DMSO concentration in reaction mixture of 0.3%) and serially diluted 3-fold into 10 stock concentrations.30 nL of each stock concentration was added to the wells with a concentration ranging from 3 µM to 0.15 nM. The reaction mixtures were incubated for 15 minutes at 24 °C and 5 µL of a solution of annealed dsDNA oligonucleotide was added to a final concentration of 50 nM. The reaction mixtures were incubated at 24 °C for 10 minutes and subsequently quenched by transferring part of the assay reaction to a solution of 100 mM ethylenediaminetetraacetic acid and 0.67% v/v Picogreen™ in a black plate with an opaque bottom. The fluorescence (emission wavelength 480 nm / excitation wavelength 520 nm) was measured using a Molecular Devices SpectraMax plate reader. Wells containing oligonucleotide but no TREX1 enzyme were used as negative controls. Wells containing oligonucleotide, TREX1 enzyme, and DMSO were used as positive controls. [00687] The data is shown in Table 2. Table 2 [00688] The examples and embodiments described herein are for illustrative purposes only and in some embodiments, various modifications or changes are to be included within the purview of disclosure and scope of the appended claims.