Quinoxaline containing RNA-targeting ligands, compositions thereof, and methods of making and using the same

Abstract

The disclosure is directed to quinoxaline containing compounds of Formula: (I) that bind to a target RNA molecule, such as a TPP riboswitch, compositions comprising the compounds, and methods of making and using the same.

Description

[0001] Attorney Docket No.: 393976-00101 QUINOXALINE CONTAINING RNA-TARGETING LIGANDS, COMPOSITIONS THEREOF, AND METHODS OF MAKING AND USING THE SAME FIELD OF INVENTION The disclosure is directed to compounds that binds to a target RNA molecule, such as a TPP riboswitch, compositions comprising the compounds, and methods of making and using the same. The compounds contain two structurally different fragments that allow for binding with the target RNA at two different binding sites, thereby producing a higher affinity binding ligand compared to compounds that only bind to a single RNA binding site. BACKGROUND The vast majority of small-molecule ligands are primarily developed to manipulate biological systems by targeting proteins. Proteins have very complex three-dimensional structures, which are critical for them to function properly, and which include clefts and pockets into which small-molecule ligands are able to bind1,2. The transcriptome – the set of all RNA molecules produced in an organism – also includes promising targets for studying and manipulating biological systems. For example, not only do RNA transcriptomes play an important role in mammalian systems, but they are also present in both bacteria and viruses and thus represent targets for small molecules to modulate gene expression. RNA can adopt three-dimensional structures of complexity rivaling that of proteins3, a key feature needed for the development of highly selective ligands4, and RNAs play pervasive roles in governing the behavior of biological systems5. Originally viewed as merely being a carrier of genetic information that exists solely to transmit a message for protein coding and guiding the process of protein biosynthesis, the modern view of RNA has evolved to encompass an expanded role, where a diverse range of RNA molecules are now understood to have broad and far-reaching roles in modulating gene expression and other biological processes by various mechanisms. Even a large number of newly discovered noncoding RNAs have been found to be associated with disease such as cancer and nontumorigenic diseases. Thus, the realization that RNAs contribute to disease states apart from coding for pathogenic proteins provides a wealth of previously unrecognized therapeutic targets. Attorney Docket No.: 393976-00101 However, even though it has been shown that small-molecule ligands can bind to mRNAs and have the potential to up- or down-regulate translation efficiency, thus tuning protein expression in cells6,7, there are challenges involved in the identification of small-molecule RNA ligands that are not faced when targeting proteins4,11,12. That also includes the development of small-molecules directed to non-coding RNAs, which also represent a rich pool of targets8–10. Unfortunately, despite the development of various techniques for the analysis of RNA structure and discovery of new function, the ability to efficiently and rapidly identify or design inhibitors that bind to and perturb the function of RNA lags far behind. Thus, there is a great need in the art to develop new methods and technologies that allow for rapid and efficient identification of small-molecule ligands that target RNA molecules. SUMMARY As already mentioned above, the transcriptome represents an attractive but underutilized set of targets for small-molecule ligands. Small-molecule ligands (and ultimately drugs) targeted to messenger RNAs and to non-coding RNAs have the potential to modulate cell state and disease. In the current disclosure, small-molecule fragments that bind a target RNA structure, such as a TPP riboswitch, with millimolar to micromolar affinities were identified. As such, one aspect of the presently disclosed subject matter is a compound of Formula (I): wherein L1 is selected ; wherein R1 and R2 are selected from the group consisting of an amine containing at least one nitrogen, and -NHR3; wherein R3is selected from the group consisting of a heterocycloalkyl containing at least one nitrogen, ethylamine, and propylamine; and any pharmaceutically acceptable salt thereof. Attorney Docket No.: 393976-00101 In some embodiments, R1 and R2 are selected from the group . below. BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 shows modification of various portions of the compounds disclosed herein, including: a) the pyridine core; b) the quinoxalin-6-ylmethanamine arm; and c) the piperazine head group. Fig. 2 shows modification of various portions of the compounds disclosed herein. DETAILED DESCRIPTION The presently disclosed subject matter will now be described more fully hereinafter. However, many modifications and other embodiments of the presently disclosed subject matter set forth herein will come to mind to one skilled in the art to which the presently disclosed subject matter pertains, having the benefit of the teachings presented in the foregoing descriptions. Therefore, it is to be understood that the presently disclosed subject matter is not to be limited to the specific embodiments disclosed and that modifications and other embodiments are intended to be included within the scope of the appended claims. In other words, the subject matter described herein covers all alternatives, modifications, and equivalents. In the event that one or more of the incorporated literature, patents, and similar materials differs from or contradicts this application, including but not limited to defined terms, term usage, described techniques, or the like, this application controls. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in this field. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. Definitions Attorney Docket No.: 393976-00101 As used herein, the term “alkyl group” refers to a saturated hydrocarbon radical containing 1 to 8, 1 to 6, 1 to 4, or 5 to 8 carbons. In some embodiments, the saturated radical contains more than 8 carbons. An alkyl group is structurally similar to a noncyclic alkane compound modified by the removal of one hydrogen from the noncyclic alkane and the substitution therefore of a non- hydrogen group or radical. Alkyl group radicals can be branched or unbranched. Lower alkyl group radicals have 1 to 4 carbon atoms. Higher alkyl group radicals have 5 to 8 carbon atoms. Examples of alkyl, lower alkyl, and higher alkyl group radicals include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec butyl, t butyl, amyl, t amyl, n-pentyl, n-hexyl, i- octyl and like radicals. As used herein, the designations “C(=O)”, “CO” and “C(O)” are used to indicate a carbonyl moiety. Examples of suitable carbonyl moieties include, but are not limited to, those found in ketones and aldehydes. The term “cycloalkyl” refers to a hydrocarbon with 3-8 members or 3-7 members or 3-6 members or 3-5 members or 3-4 members and can be monocyclic or bicyclic. The ring may be saturated or may have some degree of unsaturation. Cycloalkyl groups may be optionally substituted with one or more substituents. In one embodiment, 0, 1, 2, 3, or 4 atoms of each ring of a cycloalkyl group may be substituted by a substituent. Representative examples of cycloalkyl group include cyclopropyl, cyclopentyl, cyclohexyl, cyclobutyl, cycloheptyl, cyclopentenyl, cyclopentadienyl, cyclohexenyl, cyclohexadienyl, and the like. The term “aryl” refers to a hydrocarbon monocyclic, bicyclic or tricyclic aromatic ring system. Aryl groups may be optionally substituted with one or more substituents. In one embodiment, 0, 1, 2, 3, 4, 5 or 6 atoms of each ring of an aryl group may be substituted by a substituent. Examples of aryl groups include phenyl, naphthyl, anthracenyl, fluorenyl, indenyl, azulenyl, and the like. The term “heteroaryl” refers to an aromatic 5-10 membered ring systems where the heteroatoms are selected from O, N, or S, and the remainder ring atoms being carbon (with appropriate hydrogen atoms unless otherwise indicated). Heteroaryl groups may be optionally substituted with one or more substituents. In one embodiment, 0, 1, 2, 3, or 4 atoms of each ring of a heteroaryl group may be substituted by a substituent. Examples of heteroaryl groups include pyridyl, furanyl, thienyl, pyrrolyl, oxazolyl, oxadiazolyl, imidazolyl, thiazolyl, isoxazolyl, Attorney Docket No.: 393976-00101 quinolinyl, pyrazolyl, isothiazolyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, isoquinolinyl, indazolyl, and the like. As used herein, the term “heterocycloalkyl” refers to a nonaromatic 3-9 membered monocyclic, 7-12 membered bicyclic, or 10-14 membered tricyclic ring system comprising 1-3 heteroatoms if monocyclic, 1-6 heteroatoms if bicyclic, or 1-9 heteroatoms if tricyclic, said heteroatoms selected from O, N, S, B, P or Si, wherein the nonaromatic ring system is completely saturated. Heterocycloalkyl groups may be optionally substituted with one or more substituents. In one embodiment, 0, 1, 2, 3, or 4 atoms of each ring of a heterocycloalkyl group may be substituted by a substituent. Representative heterocycloalkyl groups include azetidine, pyrrolidine, piperidinyl, piperazinyl, 1,4-diazepane, 3,8-diazabicyclo[3.2.1]octane, tetrahydropyranyl, morpholinyl, thiomorpholinyl, 1,3-dioxolanyl, tetrahydrofuryl, tetrahydrothienyl, thienyl, and the like. As used herein, the term “substituted” refers to a moiety (such as heteroaryl, aryl, cycloalkyl, alkyl, and / or alkenyl) wherein the moiety is bonded to one or more additional organic or inorganic substituent radicals. In some embodiments, the substituted moiety comprises 1, 2, 3, 4, or 5 additional substituent groups or radicals. Suitable organic and inorganic substituent radicals include, but are not limited to, halogen, hydroxyl, alkyl, cycloalkyl, aryl, substituted aryl, heteroaryl, heterocyclic ring, substituted heterocyclic ring, amino, mono-substituted amino, di- substituted amino, acyloxy, nitro, cyano, carboxy, carboalkoxy, alkyl carboxamide, substituted alkyl carboxamide, dialkyl carboxamide, substituted dialkyl carboxamide, alkylsulfonyl, alkylsulfinyl, thioalkyl, alkoxy, substituted alkoxy or haloalkoxy radicals, wherein the terms are defined herein. Unless otherwise indicated herein, the organic substituents can comprise from 1 to 4 or from 5 to 8 carbon atoms. When a substituted moiety is bonded thereon with more than one substituent radical, then the substituent radicals may be the same or different. As used herein, the term “unsubstituted” refers to a moiety (such as heteroaryl, aryl, alkenyl, and / or alkyl) that is not bonded to one or more additional organic or inorganic substituent radical as described above, meaning that such a moiety is only substituted with hydrogens. It will be understood that the structures provided herein and any recitation of “substitution” or “substituted with” includes the implicit proviso that such structures and substitution are in accordance with permitted valence of the substituted atom and the substituent, and that the Attorney Docket No.: 393976-00101 substitution results in a stable compound, e.g., which does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, etc. As used herein, the term “RNA” refers to a ribonucleic acid which is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and DNA are nucleic acids, and, along with lipids, proteins and carbohydrates, constitute the four major macromolecules essential for all known forms of life. Like DNA, RNA is assembled as a chain of nucleotides, but unlike DNA, RNA is found in nature as a single strand folded onto itself, rather than a paired double strand. Cellular organisms use messenger RNA (mRNA) to convey genetic information (using the nitrogenous bases of guanine, uracil, adenine, and cytosine, denoted by the letters G, U, A, and C) that directs synthesis of specific proteins. Many viruses encode their genetic information using an RNA genome. Some RNA molecules play an active role within cells by catalyzing biological reactions, controlling gene expression, or sensing and communicating responses to cellular signals. One of these active processes is protein synthesis, a universal function in which RNA molecules direct the synthesis of proteins on ribosomes. This process uses transfer RNA (tRNA) molecules to deliver amino acids to the ribosome, where ribosomal RNA (rRNA) then links amino acids together to form coded proteins. As used herein, the term “non-coding RNA (ncRNA)” refers to an RNA molecule that is not translated into a protein. The DNA sequence from which a functional non-coding RNA is transcribed is often called an RNA gene. Abundant and functionally important types of non-coding RNAs include transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs), as well as small RNAs such as microRNAs, siRNAs, piRNAs, snoRNAs, snRNAs, exRNAs, scaRNAs and the long ncRNAs such as Xist and HOTAIR. As used herein, the term “coding RNA” refers to an RNA that codes for a protein, i.e., messenger RNS (mRNA). Such RNAs comprise a transcriptome. As used herein, the term “riboswitch” refers to a regulatory segment of a messenger RNA molecule that binds a small molecule, resulting in a change in production of the protein encoded by the mRNA. Thus, an mRNA that contains a riboswitch is directly involved in regulating its own activity, in response to the concentrations of its effector molecule. As used herein, the term “TPP riboswitch” also known as the THI element and Thi-box riboswitch, refers to a highly conserved RNA secondary structure. It serves as a riboswitch that binds directly to thiamine pyrophosphate (TPP) to regulate gene expression through a variety of Attorney Docket No.: 393976-00101 mechanisms in archaea, bacteria and eukaryotes. TPP is the active form of thiamine (vitamin B1), an essential coenzyme synthesized by coupling of pyrimidine and thiazole moieties in bacteria. The phrase “pharmaceutically acceptable” indicates that the substance or composition is compatible chemically and / or toxicologically, with the other ingredients comprising a formulation, and / or the subject being treated therewith. The phrase “pharmaceutically acceptable salt” as used herein, refers to pharmaceutically acceptable organic or inorganic salts of a compound of this disclosure. Exemplary salts include, but are not limited, to sulfate, citrate, acetate, oxalate, chloride, bromide, iodide, nitrate, bisulfate, phosphate, acid phosphate, isonicotinate, lactate, salicylate, acid citrate, tartrate, oleate, tannate, pantothenate, bitartrate, ascorbate, succinate, maleate, gentisinate, fumarate, gluconate, glucuronate, saccharate, formate, benzoate, glutamate, methanesulfonate “mesylate”, ethanesulfonate, benzenesulfonate, p-toluenesulfonate, pamoate (i.e., 1,1′-methylene-bis-(2- hydroxy-3-naphthoate)) salts, alkali metal (e.g., sodium and potassium) salts, alkaline earth metal (e.g., magnesium) salts, and ammonium salts. A pharmaceutically acceptable salt may involve the inclusion of another molecule such as an acetate ion, a succinate ion or other counter ion. The counter ion may be any organic or inorganic moiety that stabilizes the charge on the parent compound. Furthermore, a pharmaceutically acceptable salt may have more than one charged atom in its structure. Instances where multiple charged atoms are part of the pharmaceutically acceptable salt, the salt can have multiple counter ions. Hence, a pharmaceutically acceptable salt can have one or more charged atoms and / or one or more counter ion. “Carriers” as used herein include pharmaceutically acceptable carriers, excipients, or stabilizers that are nontoxic to the cell or mammal being exposed thereto at the dosages and concentrations employed. Often the physiologically acceptable carrier is an aqueous pH buffered solution. Non-limiting examples of physiologically acceptable carriers include buffers such as phosphate, citrate, and other organic acids; antioxidants including ascorbic acid; low molecular weight (less than about 10 residues) polypeptide; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, arginine or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextrins; chelating agents such as EDTA; sugar alcohols such as mannitol or sorbitol; salt-forming counterions such as sodium; and / or nonionic surfactants such as TWEEN™, polyethylene glycol (PEG), and PLURONICS™. In certain Attorney Docket No.: 393976-00101 embodiments, the pharmaceutically acceptable carrier is a non-naturally occurring pharmaceutically acceptable carrier. The terms “treat” and “treatment” refer to both therapeutic treatment and prophylactic or preventative measures, wherein the object is to prevent or slow down (lessen) an undesired physiological change or disorder, such as the development or spread of cancer. For purposes of this disclosure, beneficial or desired clinical results include, but are not limited to, alleviation of symptoms, diminishment of extent of disease, stabilized (i.e., not worsening) state of disease, delay or slowing of disease progression, amelioration or palliation of the disease state, and remission (whether partial or total), whether detectable or undetectable. “Treatment” can also mean prolonging survival as compared to expected survival if not receiving treatment. Those in need of treatment include those already with the condition or disorder as well as those prone to have the condition or disorder or those in which the condition or disorder is to be prevented The term “administration” or “administering” includes routes of introducing the compound(s) to a subject to perform their intended function. Examples of routes of administration which can be used include injection (including, but not limited to, subcutaneous, intravenous, parenterally, intraperitoneally, intrathecal), topical, oral, inhalation, rectal and transdermal. The term “effective amount” includes an amount effective, at dosages and for periods of time necessary, to achieve the desired result. An effective amount of compound may vary according to factors such as the disease state, age, and weight of the subject, and the ability of the compound to elicit a desired response in the subject. Dosage regimens may be adjusted to provide the optimum therapeutic response. The phrases “systemic administration,” “administered systemically”, “peripheral administration” and “administered peripherally” as used herein mean the administration of a compound(s), drug or other material, such that it enters the patient's system and, thus, is subject to metabolism and other like processes. The phrase “therapeutically effective amount” means an amount of a compound of the present disclosure that (i) treats or prevents the particular disease, condition, or disorder, (ii) attenuates, ameliorates, or eliminates one or more symptoms of the particular disease, condition, or disorder, or (iii) prevents or delays the onset of one or more symptoms of the particular disease, condition, or disorder described herein. In the case of cancer, the therapeutically effective amount of the drug may reduce the number of cancer cells; reduce the tumor size; inhibit (i.e., slow to Attorney Docket No.: 393976-00101 some extent and preferably stop) cancer cell infiltration into peripheral organs; inhibit (i.e., slow to some extent and preferably stop) tumor metastasis; inhibit, to some extent, tumor growth; and / or relieve to some extent one or more of the symptoms associated with the cancer. To the extent the drug may prevent growth and / or kill existing cancer cells, it may be cytostatic and / or cytotoxic. For cancer therapy, efficacy can be measured, for example, by assessing the time to disease progression (TTP) and / or determining the response rate (RR). The term “subject” refers to animals such as mammals, including, but not limited to, primates (e.g., humans), cows, sheep, goats, horses, dogs, cats, rabbits, rats, mice and the like. In certain embodiments, the subject is a human. The current disclosure is directed to a fragment-based ligand discovery strategy suited for the identification of small molecules that bind to specific RNA regions with high affinity. Previously, U.S. Patent Application Nos. 17 / 632,685 and 18 / 563,675, which are incorporated herein by reference in their entirety, described such a fragment-based ligand discovery strategy employed in the identification of various small molecules that specifically targeted certain RNA binding regions and is hereby incorporated by reference in its entirety. In general, fragment-based ligand discovery allows for the identification of one or more small-molecule “fragments” of low to moderate affinity that bind a target of interest. These fragments are then either elaborated or linked to create more potent ligands13,14. Typically, these fragments exhibit molecular masses of less than 300 Da and, in order to bind detectably, make substantial high-quality contacts with the target of interest. Fragment-based ligand discovery has only so far been successfully employed to identify initial hit compounds that are single fragment hits binding for a given RNA15–19. Identification of multiple fragments that bind the same RNA would make it possible to take advantage of potential additive and cooperative interactions between fragments within the binding pocket20,21. However, it has recently been shown that many RNAs bind their ligands via multiple “sub-sites”, which are regions of a binding pocket that contact a ligand in an independent or cooperative manner22. Further, it has been shown that high-affinity RNA binding can occur even when sub-site binding shows only modest cooperative effects. These features bode well for the effectiveness of fragment- based ligand discovery as applied to RNA targets. Thus, based on the above, the current disclosure is directed to methods of identifying fragments that bind to an RNA of interest, such as for example the TPP riboswitch. Second, the Attorney Docket No.: 393976-00101 disclosed methods are directed to establishing the positioning of fragment binding in the RNA at roughly nucleotide resolution. Third, the disclosed methods are directed to identifying second-site fragments that bound near the site of an initial fragment hit. The disclosed method melds the fragment-based ligand discovery approach with SHAPE-MaP RNA structure probing23,24, which was used both to identify RNA-binding fragments and to establish the individual sites of fragment binding. The ligand ultimately created by linking two fragments has no resemblance to the native riboswitch ligand, and it binds the structurally complex TPP riboswitch RNA with high affinity. The disclosed methods and the identification of ligands will be described in more detail below. A. Compounds As such, one aspect of the presently disclosed subject matter is a compound of Formula (I): wherein L1 is selected ; wherein R1 and R2 are selected from the group consisting of an amine containing at least one nitrogen, and -NHR3; wherein R3is selected from the group consisting of a heterocycloalkyl containing at least one nitrogen, ethylamine, and propylamine; and any pharmaceutically acceptable salt thereof. As in any above embodiment, a compound . Attorney Docket No.: 393976-00101 As in any above embodiment, a compound . As in any above embodiment, a compound . As in any above embodiment, a compound .As in any above embodiment, a compound optionally substituted heterocycloalkyl amine containing at least one nitrogen. As in any above embodiment, a compound wherein R1and R2are selected from the group consisting of azetidine, pyrrolidine, piperidinyl, piperazinyl, 1,4-diazepane, 3,8- diazabicyclo[3.2.1]octane, morpholinyl, and thiomorpholinyl. As in any above embodiment, a compound where the optionally substituted heterocycloalkyl amine is substituted with an ethylamine. As in any above embodiment, a compound wherein R1 and R2 are -NHR3, wherein R3 is selected from the group consisting of a heterocycloalkyl containing at least one nitrogen, ethylamine, and propylamine; and any pharmaceutically acceptable salt thereof. As in any above embodiment, a compound wherein R3 is selected from the group consisting of azetidine, pyrrolidine, piperidinyl, piperazinyl, 1,4-diazepane, 3,8-diazabicyclo[3.2.1]octane, morpholinyl, and thiomorpholinyl. As in any above embodiment, a compound wherein R3 is selected from the group consisting of azetidine and pyrrolidine. Attorney Docket No.: 393976-00101 As in any above embodiment, a compound wherein R1 and R2 are selected from the groupconsisting , any pharmaceutically acceptable salt thereof. embodiment, a compound wherein R1 and R2 are selected from the group consisting .which has a structure selected from the group consisting of , , Attorney Docket No.: 393976-00101 , , A small molecule ligand for the TPP riboswitch, compound Z1, was identified via a fragment-based screening approach coupled with SHAPE-MaP structure probing as previously described in U.S. Patent Application Nos. 17 / 632,685 and 18 / 563,675.25Although a co-crystal structures of individual fragments was obtained as well as two, less potent linked compounds bound to the TPP riboswitch, no co-crystal structure of Z1 was obtained. Z1 was dissected into three distinct units – the pyridine core, the quinoxalin-6- ylmethanamine arm, and the piperazine head group. Evaluation of a benzene core in place of the pyridine showed a loss in binding activity (Fig. 1, Table 1). Replacing the quinoxalin-6- ylmethanamine with other heterocyclic amines such as quinazoline and pyrazine hindered ligand potency (Fig.1, Table 2). Quinoxaline-6-amine maintained the quinoxaline heterocycle but deleted a single methylene in the linker, which led to reduction in binding affinity (Fig. 1, Table 3). Next was modifications of the substitution on the pyridine core. Despite maintaining both the piperazine and quinoxaline component, the two 2,4-isomer analogs had diminished binding affinity compared to Z1. Furthermore, maintenance of the original 3,4-substiution pattern but Attorney Docket No.: 393976-00101 swapping of the quinoxaline and piperazine moieties led to a significant reduction in binding (Fig. 1). The use of more potent head groups, as described further herein, in the alternative 2,4- substiution pattern was similarly less optimal than the analogous 3,4-substituted compounds (see compounds 12, 1314 in Table 4). Derivatization of the head group is described in Fig.2. Affinity for the TPP riboswitch was propelled by the presence of a basic nitrogen atom in the head group. Steric variations were also tried. Replacing the piperazine head group with 4-aminopiperidine reduced binding affinity. Furthermore, several other analogs that extended the distance between the two nitrogen atoms in the head group demonstrated an inverse relationship between the distance between the two nitrogen atoms and binding affinity, suggesting steric limitations at that position (see compounds 26, 27, 28 in Table 6). Even the appendage of an additional amine on the piperazine that introduced another basic moiety but increased the head group size also reduced ligand potency (Fig. 2). Alternative strategies to increase the basicity of the piperazine nitrogen, such as using 1- methylpiperazine, also exhibited lower binding affinity (Fig.2). This strategy to increase basicity, which came with the cost of increasing steric bulk at the nitrogen atom, led to less potent compounds when applied to the 2-aminopiperidine analog as well (see compound 31 in Table 6). Without being bound by theory, it is believed there are steric limitations at that site, even in instances when basicity is enhanced. Alternative conformational analogs of the piperazine head group were tried. More structurally rigid piperazines such as (S)-2-methylpiperazine and 3,8-diazbicyclo[3.2.1]octane provided less potent analogs (Fig.2). On the other hand, complete elimination of conformational constraints by using acyclic amines also did not improve binding (see compounds 38 and 39 in Table 8). Replacement of the piperazine group with 2,6-diazaspiro[3.3]heptane provided similar binding affinity to the parent compound, Z1, while the use of a homopiperazine head group slightly improved the binding affinity (Fig.2). Next, azetidines and pyrrolidines bearing exocyclic amines (Fig. 2) were prepared.26These analogs proved promising as they also had binding affinities similar to Z1. Smaller heterocycles bearing exocyclic amines allowed synthesis of analogs with an inverted connection (Fig. 2 and Table 9). Inverting the head group connectivity of the azetidine led to significant reduction in the binding affinity. Furthermore, an ether linkage could be used as Attorney Docket No.: 393976-00101 well, albeit with slight reduction in binding affinity. This modification was particularly intriguing considering that oxygen atoms are less prevalent in small molecules that bind to RNA.27C. Compositions Compounds as disclosed herein can be formulated in accordance with standard pharmaceutical practice as a pharmaceutical composition. According to this aspect, there is provided a pharmaceutical composition comprising a compound as disclosed herein in association with a pharmaceutically acceptable diluent or carrier. A typical formulation is prepared by mixing a compound as disclosed herein and a carrier, diluent, or excipient. Suitable carriers, diluents and excipients are well known to those skilled in the art and include materials such as carbohydrates, waxes, water soluble and / or swellable polymers, hydrophilic or hydrophobic materials, gelatin, oils, solvents, water and the like. The particular carrier, diluent or excipient used will depend upon the means and purpose for which the compound is being applied. Solvents are generally selected based on solvents recognized by persons skilled in the art as safe (GRAS) to be administered to a mammal. In general, safe solvents are non-toxic aqueous solvents such as water and other non-toxic solvents that are soluble or miscible in water. Suitable aqueous solvents include water, ethanol, propylene glycol, polyethylene glycols (e.g., PEG 400, PEG 300), etc. and mixtures thereof. The formulations may also include one or more buffers, stabilizing agents, surfactants, wetting agents, lubricating agents, emulsifiers, suspending agents, preservatives, antioxidants, opaquing agents, glidants, processing aids, colorants, sweeteners, perfuming agents, flavoring agents and other known additives to provide an elegant presentation of the drug (i.e., a compound as disclosed herein or pharmaceutical composition thereof) or aid in the manufacturing of the pharmaceutical product (i.e., medicament). The formulations may be prepared using conventional dissolution and mixing procedures. For example, the bulk drug substance (i.e., compound as disclosed herein or stabilized form of the compound (e.g., complex with a cyclodextrin derivative or other known complexation agent) is dissolved in a suitable solvent in the presence of one or more of the excipients described above. The compound is typically formulated into pharmaceutical dosage forms to provide an easily controllable dosage of the drug and to enable patient compliance with the prescribed regimen. The pharmaceutical composition (or formulation) for application may be packaged in a variety of ways depending upon the method used for administering the drug. Generally, an article for distribution includes a container having deposited therein the pharmaceutical formulation in an Attorney Docket No.: 393976-00101 appropriate form. Suitable containers are well known to those skilled in the art and include materials such as bottles (plastic and glass), sachets, ampoules, plastic bags, metal cylinders, and the like. The container may also include a tamper-proof assemblage to prevent indiscreet access to the contents of the package. In addition, the container has deposited thereon a label that describes the contents of the container. The label may also include appropriate warnings. Pharmaceutical formulations may be prepared for various routes and types of administration. For example, a compound as disclosed herein having the desired degree of purity may optionally be mixed with pharmaceutically acceptable diluents, carriers, excipients or stabilizers (Remington's Pharmaceutical Sciences (1980) 16th edition, Osol, A. Ed.), in the form of a lyophilized formulation, milled powder, or an aqueous solution. Formulation may be conducted by mixing at ambient temperature at the appropriate pH, and at the desired degree of purity, with physiologically acceptable carriers, i.e., carriers that are non-toxic to recipients at the dosages and concentrations employed. The pH of the formulation depends mainly on the particular use and the concentration of compound but may range from about 3 to about 8. Formulation in an acetate buffer at pH 5 is a suitable embodiment. The compounds can be sterile. In particular, formulations to be used for in vivo administration should be sterile. Such sterilization is readily accomplished by filtration through sterile filtration membranes. The compound ordinarily can be stored as a solid composition, a lyophilized formulation or as an aqueous solution. The pharmaceutical compositions comprising a compound as disclosed herein can be formulated, dosed and administered in a fashion, i.e., amounts, concentrations, schedules, course, vehicles and route of administration, consistent with good medical practice. Factors for consideration in this context include the particular disorder being treated, the particular mammal being treated, the clinical condition of the individual patient, the cause of the disorder, the site of delivery of the agent, the method of administration, the scheduling of administration, and other factors known to medical practitioners. The “therapeutically effective amount” of the compound to be administered will be governed by such considerations, and is the minimum amount necessary to prevent, ameliorate, or treat the coagulation factor mediated disorder. Such amount is preferably below the amount that is toxic to the host or renders the host significantly more susceptible to bleeding. Attorney Docket No.: 393976-00101 Acceptable diluents, carriers, excipients and stabilizers are nontoxic to recipients at the dosages and concentrations employed, and include buffers such as phosphate, citrate and other organic acids; antioxidants including ascorbic acid and methionine; preservatives (such as octadecyldimethylbenzyl ammonium chloride; hexamethonium chloride; benzalkonium chloride, benzethonium chloride; phenol, butyl or benzyl alcohol; alkyl parabens such as methyl or propyl paraben; catechol; resorcinol; cyclohexanol; 3-pentanol; and m-cresol); low molecular weight (less than about 10 residues) polypeptides; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, histidine, arginine, or lysine; monosaccharides, disaccharides and other carbohydrates including glucose, mannose, or dextrins; chelating agents such as EDTA; sugars such as sucrose, mannitol, trehalose or sorbitol; salt-forming counter-ions such as sodium; metal complexes (e.g., Zn-protein complexes); and / or non-ionic surfactants such as TWEEN™, PLURONICS™ or polyethylene glycol (PEG). The active pharmaceutical ingredients may also be entrapped in microcapsules prepared, for example, by coacervation techniques or by interfacial polymerization, for example, hydroxymethylcellulose or gelatin-microcapsules and poly- (methylmethacylate) microcapsules, respectively, in colloidal drug delivery systems (for example, liposomes, albumin microspheres, microemulsions, nano-particles and nanocapsules) or in macroemulsions. Such techniques are disclosed in Remington's Pharmaceutical Sciences 16th edition, Osol, A. Ed. (1980). Sustained-release preparations of compounds may be prepared. Suitable examples of sustained-release preparations include semipermeable matrices of solid hydrophobic polymers containing a compound as disclosed herein, which matrices are in the form of shaped articles, e.g., films, or microcapsules. Examples of sustained-release matrices include polyesters, hydrogels (for example, poly(2-hydroxyethyl-methacrylate), or poly(vinyl alcohol)), polylactides (U.S. Pat. No. 3,773,919), copolymers of L-glutamic acid and gamma-ethyl-L-glutamate, non-degradable ethylene-vinyl acetate, degradable lactic acid-glycolic acid copolymers such as the LUPRON DEPOT™ (injectable microspheres composed of lactic acid-glycolic acid copolymer and leuprolide acetate) and poly-D-(−)-3-hydroxybutyric acid. The formulations include those suitable for the administration routes detailed herein. The formulations may conveniently be presented in unit dosage form and may be prepared by any of the methods well known in the art of pharmacy. Techniques and formulations generally are found Attorney Docket No.: 393976-00101 in Remington's Pharmaceutical Sciences (Mack Publishing Co., Easton, Pa.). Such methods include the step of bringing into association the active ingredient with the carrier which constitutes one or more accessory ingredients. In general, the formulations are prepared by uniformly and intimately bringing into association the active ingredient with liquid carriers or finely divided solid carriers or both, and then, if necessary, shaping the product. Formulations of a compound as disclosed herein suitable for oral administration may be prepared as discrete units such as pills, capsules, cachets or tablets each containing a predetermined amount of a compound. Compressed tablets may be prepared by compressing in a suitable machine the active ingredient in a free-flowing form such as a powder or granules, optionally mixed with a binder, lubricant, inert diluent, preservative, surface active or dispersing agent. Molded tablets may be made by molding in a suitable machine a mixture of the powdered active ingredient moistened with an inert liquid diluent. The tablets may optionally be coated or scored and optionally are formulated so as to provide slow or controlled release of the active ingredient therefrom. Tablets, troches, lozenges, aqueous or oil suspensions, dispersible powders or granules, emulsions, hard or soft capsules, e.g., gelatin capsules, syrups or elixirs may be prepared for oral use. Formulations of compounds as disclosed herein intended for oral use may be prepared according to any method known to the art for the manufacture of pharmaceutical compositions and such compositions may contain one or more agents including sweetening agents, flavoring agents, coloring agents and preserving agents, in order to provide a palatable preparation. Tablets containing the active ingredient in admixture with non-toxic pharmaceutically acceptable excipient which are suitable for manufacture of tablets are acceptable. These excipients may be, for example, inert diluents, such as calcium or sodium carbonate, lactose, calcium or sodium phosphate; granulating and disintegrating agents, such as maize starch, or alginic acid; binding agents, such as starch, gelatin or acacia; and lubricating agents, such as magnesium stearate, stearic acid or talc. Tablets may be uncoated or may be coated by known techniques including microencapsulation to delay disintegration and adsorption in the gastrointestinal tract and thereby provide a sustained action over a longer period. For example, a time delay material such as glyceryl monostearate or glyceryl distearate alone or with a wax may be employed. For treatment of the eye or other external tissues, e.g., mouth and skin, the formulations may be applied as a topical ointment or cream containing the active ingredient(s) in an amount of, Attorney Docket No.: 393976-00101 for example, 0.075 to 20% w / w. When formulated in an ointment, the active ingredients may be employed with either a paraffinic or a water-miscible ointment base. Alternatively, the active ingredients may be formulated in a cream with an oil-in-water cream base. If desired, the aqueous phase of the cream base may include a polyhydric alcohol, i.e., an alcohol having two or more hydroxyl groups such as propylene glycol, butane 1,3-diol, mannitol, sorbitol, glycerol and polyethylene glycol (including PEG 400), and mixtures thereof. The topical formulations may desirably include a compound which enhances absorption or penetration of the active ingredient through the skin or other affected areas. Examples of such dermal penetration enhancers include dimethyl sulfoxide and related analogs. The oily phase of the emulsions may be constituted from known ingredients in a known manner. While the phase may comprise solely an emulsifier, it may also comprise a mixture of at least one emulsifier and a fat or oil, or both a fat and an oil. A hydrophilic emulsifier included together with a lipophilic emulsifier may act as a stabilizer. Together, the emulsifier(s) with or without stabilizer(s) make up the so-called emulsifying wax, and the wax together with the oil and fat make up the so-called emulsifying ointment base which forms the oily dispersed phase of the cream formulations. Emulsifiers and emulsion stabilizers suitable for use in the formulation include Tween® 60, Span® 80, cetostearyl alcohol, benzyl alcohol, myristyl alcohol, glyceryl mono-stearate and sodium lauryl sulfate. Aqueous suspensions of compounds contain the active materials in admixture with excipients suitable for the manufacture of aqueous suspensions. Such excipients include a suspending agent, such as sodium carboxymethylcellulose, croscarmellose, povidone, methylcellulose, hydroxypropyl methylcellulose, sodium alginate, polyvinylpyrrolidone, gum tragacanth and gum acacia, and dispersing or wetting agents such as a naturally occurring phosphatide (e.g., lecithin), a condensation product of an alkylene oxide with a fatty acid (e.g., polyoxyethylene stearate), a condensation product of ethylene oxide with a long chain aliphatic alcohol (e.g., heptadecaethyleneoxycetanol), a condensation product of ethylene oxide with a partial ester derived from a fatty acid and a hexitol anhydride (e.g., polyoxyethylene sorbitan monooleate). The aqueous suspension may also contain one or more preservatives such as ethyl or n-propyl p-hydroxybenzoate, one or more coloring agents, one or more flavoring agents and one or more sweetening agents, such as sucrose or saccharin. Attorney Docket No.: 393976-00101 The pharmaceutical compositions of compounds may be in the form of a sterile injectable preparation, such as a sterile injectable aqueous or oleaginous suspension. This suspension may be formulated according to the known art using those suitable dispersing or wetting agents and suspending agents which have been mentioned above. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally acceptable diluent or solvent, such 1,3-butanediol. The sterile injectable preparation may also be prepared as a lyophilized powder. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution and isotonic sodium chloride solution. In addition, sterile fixed oils may conventionally be employed as a solvent or suspending medium. For this purpose, any bland fixed oil may be employed including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid may likewise be used in the preparation of injectables. The amount of active ingredient that may be combined with the carrier material to produce a single dosage form will vary depending upon the host treated and the particular mode of administration. For example, a time-release formulation intended for oral administration to humans may contain approximately 1 to 1000 mg of active material compounded with an appropriate and convenient amount of carrier material which may vary from about 5 to about 95% of the total compositions (weight:weight). The pharmaceutical composition can be prepared to provide easily measurable amounts for administration. For example, an aqueous solution intended for intravenous infusion may contain from about 1 to 500 μg of the active ingredient per milliliter of solution in order that infusion of a suitable volume at a rate of about 10 mL / hr to about 50 mL / hr can occur. Formulations suitable for parenteral administration include aqueous and non-aqueous sterile injection solutions which may contain anti-oxidants, buffers, bacteriostats and solutes which render the formulation isotonic with the blood of the intended recipient; and aqueous and non- aqueous sterile suspensions which may include suspending agents and thickening agents. Formulations suitable for topical administration to the eye also include eye drops wherein the active ingredient is dissolved or suspended in a suitable carrier, especially an aqueous solvent for the active ingredient. The active ingredient is preferably present in such formulations in a concentration of about 0.5 to 20% w / w, for example about 0.5 to 10% w / w, for example about 1.5% w / w. Formulations suitable for topical administration in the mouth include lozenges comprising the active ingredient in a flavored basis, usually sucrose and acacia or tragacanth; pastilles Attorney Docket No.: 393976-00101 comprising the active ingredient in an inert basis such as gelatin and glycerin, or sucrose and acacia; and mouthwashes comprising the active ingredient in a suitable liquid carrier. Formulations for rectal administration may be presented as a suppository with a suitable base comprising for example cocoa butter or a salicylate. Formulations suitable for intrapulmonary or nasal administration have a particle size for example in the range of 0.1 to 500 microns (including particle sizes in a range between 0.1 and 500 microns in increments microns such as 0.5, 1, 30 microns, 35 microns, etc.), which is administered by rapid inhalation through the nasal passage or by inhalation through the mouth so as to reach the alveolar sacs. Suitable formulations include aqueous or oily solutions of the active ingredient. Formulations suitable for aerosol or dry powder administration may be prepared according to conventional methods and may be delivered with other therapeutic agents such as compounds heretofore used in the treatment or prophylaxis disorders as described below. Formulations suitable for vaginal administration may be presented as pessaries, tampons, creams, gels, pastes, foams or spray formulations containing in addition to the active ingredient such carriers as are known in the art to be appropriate. The formulations may be packaged in unit-dose or multi-dose containers, for example sealed ampoules and vials, and may be stored in a freeze-dried (lyophilized) condition requiring only the addition of the sterile liquid carrier, for example water, for injection immediately prior to use. Extemporaneous injection solutions and suspensions are prepared from sterile powders, granules and tablets of the kind previously described. Preferred unit dosage formulations are those containing a daily dose or unit daily sub-dose, as herein above recited, or an appropriate fraction thereof, of the active ingredient. The subject matter further provides veterinary compositions comprising at least one active ingredient as above defined together with a veterinary carrier therefore. Veterinary carriers are materials useful for the purpose of administering the composition and may be solid, liquid or gaseous materials which are otherwise inert or acceptable in the veterinary art and are compatible with the active ingredient. These veterinary compositions may be administered parenterally, orally or by any other desired route. In particular embodiments, the pharmaceutical composition comprising the presently disclosed compounds further comprise a chemotherapeutic agent. In some of these embodiments, the chemotherapeutic agent is an immunotherapeutic agent. Attorney Docket No.: 393976-00101 D. Methods of Treating The compounds and compositions disclosed herein can also be used in methods for treating various diseases and / or disorders that have been identified as being associated with a dysfunction in RNA expression and / or function, or with the expression and / or function of the protein that is produced from an mRNA, or with a useful role of switching the conformation of an RNA using a small molecule, or with changing the native function of a riboswitch as a way inhibiting growth of an infectious organism. As such, the methods of the current disclosure are directed to treating a disease or disorder that is associated with a dysfunction in RNA expression and / or function or creating a new switchable therapeutic. See, for example, US. Patent Application Publication No. 2018 / 010146, which is hereby incorporated by reference it its entirety. As such, in some embodiments, methods for treating a disease or disorder as disclosed herein (e.g., that is associated with a dysfunction in RNA expression and / or function) comprises administering to a subject in need thereof a dose of a therapeutically effective amount of a compound and / or composition as disclosed herein. A dysfunction in RNA expression is characterized by an overexpression or underexpression of one or more RNA molecule(s). In some embodiments, the one or more RNA molecule(s) are related to promoting the disease and / or disorder to be treated. In some embodiments, the RNA molecule(s) are characterized as being part of the machinery of healthy cells and thus would prevent and / or ameliorate the disease and / or disorder to be treated. In some embodiments, the disease or disorder to be treated is associated with a dysfunction in RNA function related to transcription, processing, and / or translation. In some embodiments, the disease or disorder to be treated is associated with an inaccurate expression of proteins as a result of dysfunctional RNA molecule function. In some embodiments, the disease or disorder to be treated is associated with a dysfunction of the RNA function related to gene expression. In some embodiments, the disease or disorder is a disease or disorder where it is desired to lower protein expression by binding a molecule to the mRNA. In some embodiments, the disease is advantageously treated by a therapy that can be switched on or off using a small molecule. For example, in some embodiments, the disease or disorder is a genetic disease, where it is desired to have the ability to switch expression of a therapeutic gene on or off. Attorney Docket No.: 393976-00101 The diseases and disorders to be treated include, but are not limited to, degenerative disorders, cancer, diabetes, autoimmune disorders, cardiovascular disorders, clotting disorders, diseases of the eye, infectious disease, and diseases caused by mutations in one or more genes. Exemplary degenerative diseases include, but are not limited to, Alzheimer's disease (AD), Amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease), Cancers, Charcot–Marie–Tooth disease (CMT), Chronic traumatic encephalopathy, Cystic fibrosis, Some cytochrome c oxidase deficiencies (often the cause of degenerative Leigh syndrome), Ehlers–Danlos syndrome, Fibrodysplasia ossificans progressive, Friedreich's ataxia, Frontotemporal dementia (FTD), Some cardiovascular diseases (e.g. atherosclerotic ones like coronary artery disease, aortic stenosis etc.), Huntington's disease, Infantile neuroaxonal dystrophy, Keratoconus (KC), Keratoglobus, Leukodystrophies, Macular degeneration (AMD), Marfan's syndrome (MFS), Some mitochondrial myopathies, Mitochondrial DNA depletion syndrome, Multiple sclerosis (MS), Multiple system atrophy, Muscular dystrophies (MD), Neuronal ceroid lipofuscinosis, Niemann–Pick diseases, Osteoarthritis, Osteoporosis, Parkinson's disease, Pulmonary arterial hypertension, All prion diseases (Creutzfeldt-Jakob disease, fatal familial insomnia etc.), Progressive supranuclear palsy, Retinitis pigmentosa (RP), Rheumatoid arthritis, Sandhoff Disease, Spinal muscular atrophy (SMA, motor neuron disease), Subacute sclerosing panencephalitis, Tay–Sachs disease, and Vascular dementia (might not itself be neurodegenerative, but often appears alongside other forms of degenerative dementia). Exemplary cancers include, but are not limited to, all forms of carcinomas, melanomas, blastomas, sarcomas, lymphomas and leukemias, including without limitation, bladder cancer, bladder carcinoma, brain tumors, breast cancer, cervical cancer, colorectal cancer, esophageal cancer, endometrial cancer, hepatocellular carcinoma, laryngeal cancer, lung cancer, osteosarcoma, ovarian cancer, pancreatic cancer, prostate cancer, renal carcinoma and thyroid cancer, acute lymphocytic leukemia, acute myeloid leukemia, ependymoma, Ewing's sarcoma, glioblastoma, medulloblastoma, neuroblastoma, osteosarcoma, rhabdomyosarcoma, rhabdoid cancer, and nephroblastoma (Wilm's tumor). Exemplary autoimmune disorder include, but are not limited to, Adult Still's disease, Agammaglobulinemia, Alopecia areata, Amyloidosis, Ankylosing spondylitis, Anti-GBM / Anti- TBM nephritis, Antiphospholipid syndrome, Autoimmune angioedema, Autoimmune dysautonomia, Autoimmune encephalomyelitis, Autoimmune hepatitis, Autoimmune inner ear Attorney Docket No.: 393976-00101 disease (AIED), Autoimmune myocarditis, Autoimmune oophoritis, Autoimmune orchitis, Autoimmune pancreatitis, Autoimmune retinopathy, Autoimmune urticarial, Axonal & neuronal neuropathy (AMAN), Baló disease, Behcet’s disease, Benign mucosal pemphigoid, Bullous pemphigoid, Castleman disease (CD), Celiac disease, Chagas disease, Chronic inflammatory demyelinating polyneuropathy (CIDP), Chronic recurrent multifocal osteomyelitis (CRMO), Churg-Strauss Syndrome (CSS) or Eosinophilic Granulomatosis (EGPA), Cicatricial pemphigoid, Cogan’s syndrome, Cold agglutinin disease, Congenital heart block, Coxsackie myocarditis, CREST syndrome, Crohn’s disease, Dermatitis herpetiformis, Dermatomyositis, Devic’s disease (neuromyelitis optica), Discoid lupus, Dressler’s syndrome, Endometriosis, Eosinophilic esophagitis (EoE), Eosinophilic fasciitis, Erythema nodosum, Essential mixed cryoglobulinemia, Evans syndrome, Fibromyalgia, Fibrosing alveolitis, Giant cell arteritis (temporal arteritis), Giant cell myocarditis, Glomerulonephritis, Goodpasture’s syndrome, Granulomatosis with Polyangiitis, Graves’ disease, Guillain-Barre syndrome, Hashimoto’s thyroiditis, Hemolytic anemia, Henoch- Schonlein purpura (HSP), Herpes gestationis or pemphigoid gestationis (PG), Hidradenitis Suppurativa (HS) (Acne Inversa), Hypogammalglobulinemia, IgA Nephropathy, IgG4-related sclerosing disease, Immune thrombocytopenic purpura (ITP), Inclusion body myositis (IBM), Interstitial cystitis (IC), Juvenile arthritis, Juvenile diabetes (Type 1 diabetes), Juvenile myositis (JM), Kawasaki disease, Lambert-Eaton syndrome, Leukocytoclastic vasculitis, Lichen planus, Lichen sclerosus, Ligneous conjunctivitis, Linear IgA disease (LAD), Lupus, Lyme disease chronic, Meniere’s disease, Microscopic polyangiitis (MPA), Mixed connective tissue disease (MCTD), Mooren’s ulcer, Mucha-Habermann disease, Multifocal Motor Neuropathy (MMN) or MMNCB, Multiple sclerosis, Myasthenia gravis, Myositis, Narcolepsy, Neonatal Lupus, Neuromyelitis optica, Neutropenia, Ocular cicatricial pemphigoid, Optic neuritis, Palindromic rheumatism (PR), PANDAS, Paraneoplastic cerebellar degeneration (PCD), Paroxysmal nocturnal hemoglobinuria (PNH), Parry Romberg syndrome, Pars planitis (peripheral uveitis), Parsonage- Turner syndrome, Pemphigus, Peripheral neuropathy, Perivenous encephalomyelitis, Pernicious anemia (PA), POEMS syndrome, Polyarteritis nodosa, Polyglandular syndromes type I, II, III, Polymyalgia rheumatic, Polymyositis, Postmyocardial infarction syndrome, Postpericardiotomy syndrome, Primary biliary cirrhosis, Primary sclerosing cholangitis, Progesterone dermatitis, Psoriasis, Psoriatic arthritis, Pure red cell aplasia (PRCA), Pyoderma gangrenosum, Raynaud’s phenomenon, Reactive Arthritis, Reflex sympathetic dystrophy, Relapsing polychondritis, Attorney Docket No.: 393976-00101 Restless legs syndrome (RLS), Retroperitoneal fibrosis, Rheumatic fever, Rheumatoid arthritis, Sarcoidosis, Schmidt syndrome, Scleroderma, Sjögren’s syndrome, Sperm & testicular autoimmunity, Stiff person syndrome (SPS), Subacute bacterial endocarditis (SBE), Susac’s syndrome, Sympathetic ophthalmia (SO), Takayasu’s arteritis, Temporal arteritis / Giant cell arteritis, Thrombocytopenic purpura (TTP), Tolosa-Hunt syndrome (THS), Transverse myelitis, Type 1 diabetes, Ulcerative colitis (UC), Undifferentiated connective tissue disease (UCTD), Uveitis, Vasculitis, Vitiligo, and Vogt-Koyanagi-Harada Disease. Exemplary cardiovascular disorders include, but are not limited to, coronary artery disease (CAD), angina, myocardial infarction, stroke, heart attack, heart failure, hypertensive heart disease, theumatic heart disease, cardiomyopathy, abnormal heart rythyms, congenital heart disease, valvular heart disease, carditis, aortic aneurysms, peripheral artery disease, thromboembolic disease, and venous thrombosis. Exemplary clotting disorders include, but are not limited to, hemophilia, von Willebrand diseases, disseminated intravascular coagulation, liver disease, overdevelopment of circulating anticoagulants, vitamin K deficiency, platelet disfunction, and other clotting deficiencies. Exemplary eye diseases include, but are not limited to, macular degeneration, bulging eye, cataract, CMV retinitis, diabetic macular edema, glaucoma, keratoconus, ocular hypertension, ocular migraine, retinoblastoma, subconjunctival hemorrhage, pterygium, keratitis, dry eye, and corneal abrasion. Exemplary infectious diseases include, but are not limited to, Acute Flaccid Myelitis (AFM),Anaplasmosis, Anthrax, Babesiosis, Botulism, Brucellosis, Campylobacteriosis, Carbapenem-resistant Infection (CRE / CRPA), Chancroid, Chikungunya Virus Infection (Chikungunya), Chlamydia, Ciguatera (Harmful Algae Blooms (HABs)), Clostridium Difficile Infection, Clostridium Perfringens (Epsilon Toxin), Coccidioidomycosis fungal infection (Valley fever), COVID-19 (Coronavirus Disease 2019), Creutzfeldt-Jacob Disease, transmissible spongiform encephalopathy (CJD), Cryptosporidiosis (Crypto), Cyclosporiasis, Dengue, 1,2,3,4 (Dengue Fever), Diphtheria, E. coli infection, Shiga toxin-producing (STEC), Eastern Equine Encephalitis (EEE) , Ebola Hemorrhagic Fever (Ebola), Ehrlichiosis, Encephalitis, Arboviral or parainfectious, Enterovirus Infection , Non-Polio (Non-Polio Enterovirus), Enterovirus Infection , D68 (EV-D68), Giardiasis (Giardia), Glanders, Gonococcal Infection (Gonorrhea), Granuloma inguinale, Haemophilus Influenza disease, Type B (Hib or H-flu), Hantavirus Pulmonary Attorney Docket No.: 393976-00101 Syndrome (HPS), Hemolytic Uremic Syndrome (HUS), Hepatitis A (Hep A), Hepatitis B (Hep B), Hepatitis C (Hep C), Hepatitis D (Hep D), Hepatitis E (Hep E), Herpes, Herpes Zoster, zoster VZV (Shingles), Histoplasmosis infection (Histoplasmosis), Human Immunodeficiency Virus / AIDS (HIV / AIDS), Human Papillomavirus (HPV), Influenza (Flu), Lead Poisoning, Legionellosis (Legionnaires Disease), Leprosy (Hansens Disease), Leptospirosis, Listeriosis (Listeria), Lyme Disease, Lymphogranuloma venereum infection (LGV), Malaria, Measles, Melioidosis, Meningitis, Viral (Meningitis, viral), Meningococcal Disease , Bacterial (Meningitis, bacterial), Middle East Respiratory Syndrome Coronavirus (MERS-CoV), Mumps, Norovirus, Paralytic Shellfish Poisoning (Paralytic Shellfish Poisoning, Ciguatera), Pediculosis (Lice, Head and Body Lice), Pelvic Inflammatory Disease (PID), Pertussis (Whooping Cough), Plague; Bubonic, Septicemic, Pneumonic (Plague), Pneumococcal Disease (Pneumonia), Poliomyelitis (Polio), Powassan, Psittacosis (Parrot Fever), Pthiriasis (Crabs; Pubic Lice Infestation), Pustular Rash diseases (Small pox, monkeypox, cowpox), Q-Fever, Rabies, Ricin Poisoning, Rickettsiosis (Rocky Mountain Spotted Fever), Rubella, Including congenital (German Measles), Salmonellosis gastroenteritis (Salmonella), Scabies Infestation (Scabies), Scombroid, Septic Shock (Sepsis), Severe Acute Respiratory Syndrome (SARS), Shigellosis gastroenteritis (Shigella), Smallpox, Staphyloccal Infection, Methicillin-resistant (MRSA), Staphylococcal Food Poisoning, Enterotoxin - B Poisoning (Staph Food Poisoning), Staphylococcal Infection, Vancomycin Intermediate (VISA), Staphylococcal Infection, Vancomycin Resistant (VRSA), Streptococcal Disease , Group A (invasive) (Strep A (invasive)), Streptococcal Disease, Group B (Strep-B), Streptococcal Toxic-Shock Syndrome, STSS, Toxic Shock (STSS, TSS), Syphilis (primary, secondary, early latent, late latent, congenital), Tetanus Infection, tetani (Lock Jaw), Trichomoniasis (Trichomonas infection), Trichonosis Infection (Trichinosis), Tuberculosis (TB), Tuberculosis (Latent) (LTBI), Tularemia (Rabbit fever), Typhoid Fever (Group D), Typhus, Vaginosis , bacterial (Yeast Infection), Vaping-Associated Lung Injury (e-Cigarette Associated Lung Injury), Varicella (Chickenpox), Vibrio cholerae (Cholera), Vibriosis (Vibrio), Viral Hemorrhagic Fever (Ebola, Lassa, Marburg), West Nile Virus, Yellow Fever, Yersenia (Yersinia), and Zika Virus Infection (Zika). EXAMPLES Attorney Docket No.: 393976-00101 Reactions were carried out in either round bottom flasks, microwave vials, or glass sample vials. All reagents, starting materials, and solvents (including dry solvents) were obtained from commercial suppliers and used without further purification. Thin-layer chromatography (TLC) was performed using commercial silica gel 60 F254 coated aluminum-backed sheets. Visualization was accomplished with UV light. Purification was carried out by an automated flash chromatography / medium-pressure liquid chromatography (MPLC) system using normal phase (NP) or reversed phase (RP) C-18 columns. All NMR (1H and13C) spectra were recorded on either a 400 MHz with a dual carbon / proton probe, 500 MHz spectrometer with a dual carbon / proton cryoprobe, or a 600 MHz spectrometer with a dual carbon / proton cryoprobe. NMR samples were recorded in CDCl3, CD3OD, or DMSO-d6). Chemical shifts are reported in parts per million (ppm) and referenced to the center line of residual solvent (for CDCl3, δ 7.26 ppm for1H NMR and 77.16 for13C NMR; for CD3OD, δ 3.31 for1H NMR and 49.0 ppm for13C NMR; for DMSO-d6, δ 2.50 ppm for1H NMR and 39.52 ppm for13C NMR; for CD2Cl2, δ 5.32 ppm for1H NMR and 54.00 for13C NMR; for CD3CN, δ 1.94 ppm for1H NMR and 118.26 for13C NMR ). Coupling constants are reported in Hertz (Hz). HRMS data were collected with a Q Exactive HF-X mass spectrometer and an electrospray ion source (ESI). Purity data were measured with a UPLC H-Class System coupled to a FT-ICR mass spectrometer mass with the ESI source. Compound purity was measured on the basis of peak integration (area under the curve) from UV–vis absorbance (214 or 254 nm). If not listed, the salt count for final compounds was determined by1H NMR in DMSO-d6.Example 1: Screening of small-molecule fragments The compounds disclosed herein were screened for RNA binding activity according to the assays described in U.S. Patent Application Nos. 17 / 632,685 and 18 / 563,675, and the results are shown in Tables 1-10 below. Table 1 Compound Structure Kd (μM) Attorney Docket No.: 393976-00101 Table 2 R2 IDKd (μM) a e Attorney Docket No.: 393976-00101 Compound Structure Compound IDKd (μM) Attorney Docket No.: 393976-00101 Head Group Kd (μM) Attorney Docket No.: 393976-00101 Head Kd (μM) Attorney Docket No.: 393976-00101 Head Group (R) Kd (μM) Attorney Docket No.: 393976-00101 Compound Kd (μM) a e

[0002] Attorney Docket No.: 393976-00101 Head Group CompoundKd (μM) Head Group Kd (μM) Example 2: General Synthetic Procedures Attorney Docket No.: 393976-00101 (a) General Procedure 1: Buchwald-Hartwig Route via 3,4-dibromopyridine (1.0 equiv), amine (2.5 equiv) and acetonitrile (0.8 M). The vial was heated in microwave at 180 °C for 30 min. Once cooled, the reaction was diluted with saturated NaHCO3 and extracted three times using EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated. The crude material was purified using MPLC. General Procedure 1.2. A flame-dried microwave vial was charged with the product from step 1.1, NaOtBu (1.5-3.0 equiv), Pd2dba3 (2-4 mol%), BINAP (4-8 mol%), and toluene (0.1 M). The reaction was sparged with argon for 30 minutes and then sealed. The reaction was heated at 100 °C for 16 hours. Once cooled, the reaction was diluted with saturated NaHCO3and extracted three times using EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated. The crude material was purified using MPLC. General Procedure 1.3. To a flask containing the product from step 1.2 was added DCM (0.05 M) followed by 2 M HCl in Et2O or TFA (5-25 equiv). The reaction was left to stir for 0.5- 16 hour at room temperature. The stir bar was removed and the reaction was concentrated under nitrogen to provide the desired salt. In some cases, the salt was neutralized by using MPLC. (b) General Procedure 2: Reductive Amination Route via 4-chloro-3-nitropyridine

[0003] Attorney Docket No.: 393976-00101 (1.0 equiv), amine (2.0 equiv), triethylamine (3.0 equiv), and acetonitrile (1.0 M). The reaction was refluxed for 12 hours. Once cooled, the stir bar was removed, and the contents of the flask were concentrated. The crude material was purified using MPLC. General Procedure 2.2. A round bottom flask was charged with the product from step 2.1 followed by 10 wt.% Pd / C (0.1 equiv). The flask was placed under an atmosphere of argon and MeOH (0.1 M) was added. The flask was evacuated and refilled with hydrogen three times, and the reaction was left to stir for 12 h. The reaction was filtered over celite, and the filtrate was then concentrated. The material was either directly used in the next step crude or purified using MPLC. General Procedure 2.3. To a round bottom flask containing the product from step 2.2 was added quinoxaline-6-carbaldehyde (1.1 equiv) followed by MeOH or EtOH (0.1 M). The reaction was refluxed for 16 h or until UPLC or TLC indicated complete imine formation. The flask was cooled to 0 °C, and NaBH4 (2.0 - 5.0 equiv) was added portion-wise. After stirring for 2-6 hours, the reaction was diluted with sat. NaHCO3solution and extracted three times with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated. The crude material was purified using MPLC. General Procedure 2.4. To a flask containing the product from step 2.3 was added DCM (0.05 M) followed by 2 M HCl in Et2O or TFA (5-25 equiv). The reaction was left to stir for 0.5- 16 hour at room temperature. The stir bar was removed and the reaction was concentrated under nitrogen to provide the desired salt. In some cases, the salt was neutralized by using RP MPLC (MeOH / 0.1% NH3in H2O; 10-100%). Attorney Docket No.: 393976-00101 Example 3: Synthesis of tert-butyl 4-(3- 4-yl)piperazine-1-carboxylate Prepared using the general procedure 1.1 using 3,4-dibromopyridine (2.0 g, 8.4 mmol), tert-butyl piperazine-1-carboxylate (3.9 g, 21.1 mmol), and acetonitrile (10.6 mL). The crude material was purified using NP MPLC (EtOAc / Hex; 0-100%) to provide tert-butyl 4-(3- bromopyridin-4-yl)piperazine-1-carboxylate as a white solid (1.6 g, 4.7 mmol, 57% yield).1H NMR (400 MHz, CD3OD) δ 8.51 (s, 1H), 8.31 (d, J = 5.5 Hz, 1H), 7.08 (d, J = 5.6 Hz, 1H), 3.69 – 3.53 (m, 4H), 3.25 – 3.13 (m, 4H), 1.49 (s, 9H).13C NMR (101 MHz, CD3OD) δ 158.7, 156.4, 153.5, 150.0, 117.0, 116.3, 51.2, 44.8, 28.6. HRMS (ESI, m / z): calculated for C14H21N3O2Br [M+H]+: 342.08118; found 342.08109. Example 4: Synthesis of 6-ylmethyl)amino)pyridin-4- yl)piperazine-1-carboxylate Prepared using general procedure 1.2 using tert-butyl 4-(3-bromopyridin-4-yl)piperazine- 1-carboxylate (300 mg, 0.9 mmol), quinoxalin-6-ylmethanamine (349 mg, 2.2 mmol), Pd2dba3(16 mg, 0.02 mmol) BINAP (22 mg, 0.04 mmol), NaOtBu (168 mg, 1.8 mmol), and toluene (8.0 mL). The crude product was purified using RP MPLC (MeOH / 0.1% NH3in H2O; 10-100%) then NP MPLC (MeOH / DCM; 0-10%) to provide tert-butyl 4-(3-((quinoxalin-6-ylmethyl)amino)pyridin- 4-yl)piperazine-1-carboxylate as a yellow residue (251 mg, 0.6 mmol, 68% yield).1H NMR (400 MHz, CD3OD) δ 8.85 (ABq, ∆υAB= 2.4 Hz, JAB= 2.0 Hz, 2H), 8.10 (d, J = 8.5 Hz, 1H), 8.06 – 8.01 (m, 1H), 7.91 (dd, J = 8.8, 1.9 Hz, 1H), 7.80 (d, J = 5.3 Hz, 1H), 7.68 (s, 1H), 7.00 (d, J = 5.3 Hz, 1H), 4.75 (s, 2H), 3.74 – 3.63 (m, 4H), 3.09 – 3.00 (m, 4H).13C NMR (101 MHz, CD3OD) δ 156.4, 147.8, 146.6, 146.2, 144.2, 143.9, 143.3, 140.2, 139.5, 133.0, 131.0, 130.4, 127.0, 115.2, Attorney Docket No.: 393976-00101 81.4, 50.9, 47.9, 44.9 (broad), 28.7.HRMS (ESI, m / z): calculated for C23H29N6O2 [M+H]+: 421.23468; found 421.23401. Example 5: Synthesis of 6-ylmethyl)pyridin-3-amine hydrochloride salt Prepared using general procedure 1.3 using tert-butyl 4-(3-((quinoxalin-6- ylmethyl)amino)pyridin-4-yl)piperazine-1-carboxylate (150 mg, 0.36 mmol) in DCM (18 mL) and 2 M HCl in Et2O (1.8 mL, 3.6 mmol). Concentrated under nitrogen to obtain 4-(piperazin-1-yl)- N-(quinoxalin-6-ylmethyl)pyridin-3-amine hydrochloride salt as a light brown solid (134 mg, 0.4 mmol, 96% yield).1H NMR: (400 MHz, DMSO-d6) δ 14.83 (br s, 1H), 9.57 (br s, 2H), 8.93 (s, 2H), 8.16 – 8.01 (m, 3H), 7.92 (dd, J = 8.7, 1.8 Hz, 1H), 7.78 (s, 1H), 7.40 (d, J = 6.3 Hz, 1H), 6.84 (t, J = 5.5 Hz, 1H), 4.77 (d, J = 5.5 Hz, 2H), 3.56 – 3.45 (m, 4H), 3.45 – 3.34 (m, 4H).13C NMR: (100 MHz, CD3OD) δ 153.3, 146.1, 146.1, 143.0, 142.9, 142.9, 141.2, 132.9, 131.7, 130.3, 126.7, 123.1, 116.3, 47.6, 47.0, 44.3. HRMS (ESI, m / z): calculated for C18H21N6[M+H]+: 321.18218; found 321.18213. Purity (LC): >99% Example 6: Synthesis of 3-bromo-4- pyridine Prepared using the general procedure 1.1 using 3,4-dibromopyridine (2.0 g, 8.4 mmol), piperidine (2.1 mL, 21 mmol), and acetonitrile (10.6 mL). The crude material was purified using NP MPLC (EtOAc / Hex; 0-100%) to provide 3-bromo-4-(piperidin-1-yl)pyridine as a yellow oil (1.6 g, 6.5 mmol, 77% yield).1H NMR (400 MHz, DMSO-d6) δ 8.50 (s, 1H), 8.32 (d, J = 5.4 Hz, 1H), 7.04 (d, J = 5.4 Hz, 1H), 3.23 – 2.97 (m, 4H), 1.70 – 1.62 (m, 4H), 1.60 – 1.52 (m, 2H).13C NMR (101 MHz, DMSO-d6) δ 157.0, 152.4, 149.5, 115.8, 114.7, 51.1, 25.4, 23.5. HRMS (ESI, m / z): calculated for C10H14N2Br [M+H]+: 241.03348; found 241.03294. Attorney Docket No.: 393976-00101 Example 7: Synthesis of 4- 6-ylmethyl)pyridin-3-amine Prepared using general 4-(piperidin-1-yl)pyridine (200 mg, 0.8 mmol), quinoxalin-6-ylmethanamine (264 mg, 1.7 mmol), Pd2dba3 (15 mg, 0.02 mmol) BINAP (52 mg, 0.04 mmol), NaOtBu (239 mg, 2.5 mmol), and toluene (7.5 mL). The crude product was purified using RP MPLC (MeOH / 0.1% NH3in H2O; 10-100%) then RP MPLC (MeCN / 0.1% NH3in H2O; 10-100%) to provide 4-(piperidin-1-yl)-N-(quinoxalin-6-ylmethyl)pyridin-3-amine as a yellow solid (139 mg, 0.4 mmol, 53% yield).1H NMR (400 MHz, CD3OD) δ 8.85 (ABq, ∆υAB= 2.5 Hz, JAB= 2.0 Hz, 2H), 8.10 (d, J = 8.7 Hz, 1H), 8.04 (s, 1H), 7.90 (dd, J = 8.7, 1.9 Hz, 1H), 7.79 (d, J = 5.2 Hz, 1H), 7.65 (s, 1H), 6.97 (d, J = 5.3 Hz, 1H), 4.73 (s, 2H), 3.08 – 2.98 (m, 4H), 1.87 – 1.77 (m, 4H), 1.72 – 1.60 (m, 2H).13C NMR (101 MHz, CD3OD) δ 149.6, 146.6, 146.2, 144.3, 144.0, 143.3, 140.1, 139.7, 132.4, 131.0, 130.4, 127.0, 115.0, 52.5, 48.1, 27.3, 25.4. HRMS (ESI, m / z): calculated for C19H22N5[M+H]+: 320.18698; found 320.18634. Purity (LC): 96% Example 8: Synthesis of 4-(3- Prepared using the general procedure 1.1 using 3,4-dibromopyridine (2.2 g, 8.4 mmol), morpholine (1.9 mL, 21.1 mmol) and acetonitrile (10.6 mL). The crude material was purified using RP MPLC (MeOH / 0.1% NH3 in H2O; 10-100%) to provide 4-(3-bromopyridin-4-yl)morpholine as brown oil (1.6 g, 6.6 mmol, 78 % yield).1H NMR (400 MHz, DMSO-d6) δ 8.37 (d, J = 5.4 Hz, 1H), 7.08 (d, J = 5.4 Hz, 1H), 3.90 – 3.64 (m, 4H), 3.23 – 3.06 (m, 4H).13C NMR(101 MHz, DMSO-d6) δ 155.9, 152.5, 149.6, 115.6, 114.4, 65.9, 50.1. HRMS (ESI, m / z): calculated for C9H12BrN2O [M+H]+: 243.01278; found 243.01226. Attorney Docket No.: 393976-00101 Example 9: Synthesis of 4- ylmethyl)pyridin-3-amine Prepared using general 4-yl)morpholine (360 mg, 1.5 mmol), quinoxalin-6-ylmethanamine (248 mg, 1.6 mmol), Pd2dba3(54 mg, 0.06 mmol) BINAP (92 mg, 0.12 mmol), NaOtBu (427 mg, 4.5 mmol), and toluene (13.5 mL). The crude product was purified using RP MPLC (MeCN / 0.1% NH3 in H2O; 10-100%) then NP MPLC (MeOH / DCM; 0- 10%) to provide 4-morpholino-N-(quinoxalin-6-ylmethyl)pyridin-3-amine as an amorphous yellow solid (126 mg, 0.4 mmol, 27% yield).1H NMR (400 MHz, DMSO-d6) δ 8.90 (s, 2H), 8.08 (d, J = 8.6 Hz, 1H), 8.00 (s, 1H), 7.89 (dd, J = 8.7, 1.8 Hz, 1H), 7.78 (d, J = 5.1 Hz, 1H), 7.70 (s, 1H), 6.88 (d, J = 5.1 Hz, 1H), 5.85 (t, J = 6.0 Hz, 1H), 4.69 (d, J = 6.0 Hz, 1H), 3.88 – 3.82 (m, 4H), 3.02 – 2.92 (m, 4H).13C NMR (101 MHz, DMSO-d6) δ 145.7, 145.2, 144.7, 142.8, 142.2, 141.5, 139.2, 137.0, 132.7, 129.6, 129.2, 126.0, 113.2, 66.2, 49.8, 46.1. HRMS (ESI, m / z): calculated for C18H20N5O [M+H]+: 322.16628; found 322.16583. Purity (LC): >99% Example 10: Synthesis of 1-(3- piperidine-4-carbonitrile Prepared using general procedure 1.1 using 3,4-dibromopyridine (500 mg, 2.1 mmol), piperidine-4-carbonitrile (581 mg, 5.3 mmol), and acetonitrile (2.6 mL). The crude material was purified using NP MPLC (EtOAc / Hex; 0-100%) to provide 1-(3-bromopyridin-4-yl)piperidine-4- carbonitrile as a white solid (381 mg, 1.5 mmol, 68% yield).1H NMR (400 MHz, CD2Cl2) δ 8.55 (s, 1H), 8.34 (d, J = 5.4 Hz, 1H), 6.88 (d, J = 5.4 Hz, 1H), 3.35 (ddd, J = 11.4, 7.1, 3.5 Hz, 2H), 3.08 (ddd, J = 11.9, 7.7, 3.4 Hz, 2H), 2.88 (tt, J = 8.0, 4.4 Hz, 1H), 2.16 – 1.96 (m, 4H).13C NMR (100 MHz, CD2Cl2) δ 156.6, 153.1, 149.5, 121.3, 115.6, 115.4, 48.7, 28.6, 25.9. Attorney Docket No.: 393976-00101 Example 11: Synthesis of amino)pyridin-4-yl)piperidine-4- carbonitrile Prepared using general procedure 1.2 using 1-(3-bromopyridin-4-yl)piperidine-4- carbonitrile (168 mg, 0.6 mmol, 1.0 equiv), quinoxalin-6-ylmethanamine (201 mg, 1.3 mmol, 2.0 equiv), sodium tert-butoxide (182 mg, 1.9 mmol, 3.0 equiv), BINAP (15.7 mg, 4.0 mol%), Pd2dba3 (11.6 mg, 2.0 mol%), and toluene (5.7 mL). The crude product was purified on RP MPLC (MeOH / 0.1% NH3 in H2O; 10-100%) to yield 1-(3-((quinoxalin-6-ylmethyl)amino)pyridin-4- yl)piperidine-4-carbonitrile (210 mg, 1.1 mmol, 85% yield).1H NMR (400 MHz, DMSO-d6) δ 8.90 (d, J = 1.2 Hz, 2H), 8.16 (s, 2H), 8.08 (d, J = 8.6 Hz, 1H), 8.00 (d, J = 2.0 Hz, 1H), 7.89 (dd, J = 8.6, 2.0 Hz, 1H), 7.77 (d, J = 5.0 Hz, 1H), 7.70 (s, 1H), 6.88 (d, J = 5.1 Hz, 1H), 5.82 (t, J = 6.2 Hz, 1H), 4.68 (d, J = 5.9 Hz, 2H), 3.10 (m, 3H), 2.87 (m, 2H), 2.17 – 1.95 (m, 4H).13C NMR (101 MHz, DMSO-d6) δ 163.7, 146.2, 145.7, 145.6, 143.2, 142.7, 142.0, 139.5, 137.7, 132.9, 130.1, 129.7, 126.5, 122.9, 118.5, 114.0, 48.6, 46.6, 28.8, 25.5. Example 12: Synthesis of (1-(3- piperidin-4-yl)methanol Prepared using the general procedure 1.1 using 3,4-dibromopyridine (500 mg, 2.1 mmol) and piperidin-4-ylmethanol (608 mg, 5.3 mmol) and acetonitrile (2.6 mL). The crude material was purified using RP MPLC (MeOH / 0.1% NH3 in H2O; 10-100%) to provide (1-(3-bromopyridin-4- yl)piperidin-4-yl)methanol as a white solid (455 mg, 1.7 mmol, 80% yield).1H NMR (400 MHz, DMSO-d6) δ 8.49 (s, 1H), 8.32 (d, J = 5.4 Hz, 1H), 7.04 (d, J = 5.4 Hz, 1H), 4.51 (t, J = 5.2 Hz, 1H), 3.52 (d, J = 12.1 Hz, 2H), 3.33 – 3.29 (m, 2H), 2.70 (td, J = 11.9, 1.8 Hz, 2H), 1.77 (d, J = Attorney Docket No.: 393976-00101 10.8 Hz, 2H), 1.62 – 1.48 (m, 1H), 1.30 (qd, J = 12.3, 3.8 Hz, 2H). Multiplet at 3.33 – 3.29 ppm overlaps with residual water peak.13C NMR (101 MHz, DMSO-d6) δ 156.8, 152.3, 149.4, 115.8, 114.7, 65.7, 50.2, 37.8, 28.5.HRMS (ESI, m / z): calculated for C11H16N2OBr [M+H]+: 271.04408; found 271.04395. Example 13: Synthesis of amino)pyridin-4-yl)piperidin-4- yl)methanol Prepared using general procedure 1.2 using (1-(3-bromopyridin-4-yl)piperidin-4- yl)methanol (150 mg, 0.6 mmol), quinoxalin-6-ylmethanamine (176 mg, 1.1 mmol), Pd2dba3(10 mg, 0.01 mmol) BINAP (14 mg, 0.02 mmol), NaOtBu (159 mg, 1.7 mmol), and toluene (5 mL). The crude product was purified using RP MPLC (MeOH / 0.1% NH3 in H2O; 10-100%) to yield (1- (3-((quinoxalin-6-ylmethyl)amino)pyridin-4-yl)piperidin-4-yl)methanol as a pale yellow solid (49 mg, 0.2 mmol, 25% yield).1H NMR (400 MHz, DMSO-d6) δ 8.90 (ABq, ∆υAB = 1.8 Hz, JAB = 1.9 Hz, 2H), 8.08 (d, J = 8.6 Hz, 1H), 8.00 (s, 1H), 7.88 (dd, J = 8.6, 1.7 Hz, 1H), 7.77 (d, J = 5.1 Hz, 1H), 7.69 (s, 1H), 6.86 (d, J = 5.1 Hz, 1H), 5.62 (t, J = 6.1 Hz, 1H), 4.68 (d, J = 6.0 Hz, 2H), 4.52 (t, J = 5.1 Hz, 1H), 3.38 – 3.27 (m, 4H), 2.57 (t, J = 10.9 Hz, 2H), 1.80 (d, J = 10.7 Hz, 2H), 1.60 – 1.39 (m, 3H).13C NMR (101 MHz, DMSO-d6) δ 145.9, 145.7, 145.2, 142.8, 142.2, 141.5, 139.2, 137.2, 132.5, 129.6, 129.2, 126.0, 113.4, 65.94, 49.9, 46.2, 38.3, 28.9. HRMS (ESI, m / z): calculated for C20H24N5O [M+H]+: 350.19758; found 350.19739. Purity (LC): 99% Example 14: Synthesis of 1-(3- -4-phenylpiperazine Attorney Docket No.: 393976-00101 Prepared using the general procedure 1.1 using 3,4-dibromopyridine (500 mg, 2.1 mmol), 1-phenylpiperazine (856 mg, 5.2 mmol), and acetonitrile (2.6 mL), 0.8 molar, 1 Eq, 2.1 mmol). The crude material was purified using NP MPLC (MeOH / DCM; 0-10%) to provide 1-(3- bromopyridin-4-yl)-4-phenylpiperazine as an off-white solid (502 mg, 1.6 mmol, 75% yield).1H NMR (400 MHz, CDCl3) δ 8.59 (s, 1H), 8.37 (d, J = 5.5 Hz, 1H), 7.34 – 7.28 (m, 2H), 7.02 – 6.97 (m, 2H), 6.92 – 6.88 (m, 2H), 3.38 (s, 8H).13C NMR (101 MHz, CDCl3) δ 156.7, 153.0, 151.1, 149.1, 129.3, 120.5, 116.5, 115.2, 115.1, 50.3, 49.3. HRMS: calculated for C19H22N5[M+H]+: 318.06008; found 318.05997. Example 15: Synthesis of 4- -N-(quinoxalin-6-ylmethyl)pyridin-3- amine Prepared using general procedure 1.2 using 1-(3-bromopyridin-4-yl)-4-phenylpiperazine (124 mg, 0.4 mmol), quinoxalin-6-ylmethanamine (124 mg, 0.8 mmol), Pd2dba3 (7 mg, 0.008 mmol) BINAP (24 mg, 0.04 mmol), NaOtBu (112 mg, 1.2 mmol), and toluene (3.5 mL). The crude product was purified using RP MPLC (MeOH / 0.1% NH3in H2O; 10-100%) to provide 4-(4- phenylpiperazin-1-yl)-N-(quinoxalin-6-ylmethyl)pyridin-3-amine as an orange solid (75 mg, 0.2 mmol, 49% yield).1H NMR (400 MHz, DMSO-d6) δ 8.91 (ABq, ∆υAB = 2.4 Hz, JAB = 1.9 Hz, 2H), 8.09 (d, J = 8.6 Hz, 1H), 8.02 (d, J = 1.1 Hz, 1H), 7.91 (dd, J = 8.6, 1.9 Hz, 1H), 7.80 (d, J = 5.1 Hz, 1H), 7.73 (s, 1H), 7.25 (dd, J = 8.7, 7.3 Hz, 1H), 7.02 (dd, J = 8.8, 0.8 Hz, 1H), 6.93 (d, J = 5.1 Hz, 1H), 6.81 (dd, J = 10.5, 4.1 Hz, 1H), 5.84 (t, J = 5.9 Hz, 1H), 4.71 (d, J = 5.9 Hz, 2H), 3.44 – 3.38 (m, 4H), 3.17 – 3.11 (m, 4H).13C NMR(101 MHz, CD3OD) δ 152.9, 148.2, 146.6, 146.2, 144.3, 144.0, 143.3, 140.2, 139.6, 132.8, 131.0, 130.4, 130.1, 127.0, 121.3, 117.7, 115.0, 51.0, 50.8, 48.0. HRMS (ESI, m / z): calculated for C24H25N6[M+H]+: 397.21348; found 397.21283. Purity (LC): 98% Attorney Docket No.: 393976-00101 Example 16: Synthesis of amino)pyridin-4-yl)piperidine-4- carboxamide Prepared from 1-(3-((quinoxalin-6-ylmethyl)amino)pyridin-4-yl)piperidine-4-carbonitrile (61.1 mg, 0.2 mmol, 1.0 equiv) by dissolving in MeOH (0.2 mL), THF (0.4 mL) and DI water (0.1 mL). Finally, the flask was charged with a stir bar and treated with LiOH (127 mg, 5.3 mmol, 30 equiv) and heated at reflux for 8 hours. Upon reaction completion, the crude mixture was treated with 10 mL of sat. ammonium chloride and extracted into ethyl acetate. Crude product was purified with RP MPLC (MeOH / 0.1% NH3 in H2O; 10-100%) to reveal 1-(3-((quinoxalin-6- ylmethyl)amino)pyridin-4-yl)piperidine-4-carboxamide as a colorless residue (38.1 mg, 0.1 mmol, 59% yield).1H NMR (400 MHz, DMSO-d6) δ 8.90 (q, J = 1.9 Hz, 2H), 8.08 (d, J = 8.6 Hz, 1H), 8.00 (d, J = 1.8 Hz, 1H), 7.88 (dd, J = 8.7, 1.9 Hz, 1H), 7.75 (d, J = 5.1 Hz, 1H), 7.67 (s, 1H), 6.83 (d, J = 5.1 Hz, 1H), 5.59 (t, J = 6.2 Hz, 1H), 4.68 (d, J = 6.1 Hz, 2H), 3.23 (d, J = 11.4 Hz, 2H), 2.57 (t, J = 10.8 Hz, 2H), 2.00 – 1.90 (m, 1H), 1.90 – 1.73 (m, 4H).13C NMR (101 MHz, DMSO- d6) δ 178.2, 146.7, 146.2, 145.7, 143.3, 142.7, 141.9, 139.70, 137.68, 132.8, 130.1, 129.6, 126.4, 1-yl)pyridine Prepared using the general procedure 1.1 using 3,4-dibromopyridine (500 mg, 2.1 mmol) and 4-phenylpiperidine (851 mg, 5.3 mmol) and acetonitrile (2.6 mL). The crude material was purified using NP MPLC (EtOAc / Hex; 0-100%) to obtain 3-bromo-4-(4-phenylpiperidin-1- Attorney Docket No.: 393976-00101 yl)pyridine as a white solid (410 mg, 1.3 mmol, 61% yield).1H NMR (400 MHz, DMSO-d6) δ 8.53 (s, 1H), 8.35 (d, J = 5.4 Hz, 1H), 7.37 – 7.27 (m, 4H), 7.26 – 7.18 (m, 1H), 7.11 (d, J = 5.4 Hz, 1H), 3.65 (d, J = 12.2 Hz, 2H), 2.87 (td, J = 11.9, 2.1 , 2.74 (tt, J = 11.9, 3.7 Hz, 1H), 1.91 (dd, J = 12.4, 2.2 Hz, 2H), 1.81 (qd, J = 12.2, 3.6 Hz, 2H).13C NMR (101 MHz, DMSO-d6) δ 156.7, 152.4, 149.5, 145.7, 128.4, 126.7, 126.2, 115.9, 114.7, 50.7, 41.2, 32.8. HRMS (ESI, m / z): calculated for C16H18N2Br [M+H]+: 317.06478; found 317.06421. Example 18: Synthesis of 4- -N-(quinoxalin-6-ylmethyl)pyridin-3- amine Prepared using general procedure 1.2 using 3-bromo-4-(4-phenylpiperidin-1-yl)pyridine (150 mg, 0.5 mmol), quinoxalin-6-ylmethanamine (151 mg, 1.0 mmol), Pd2dba3 (9 mg, 0.01 mmol) BINAP (12 mg, 0.02 mmol), NaOtBu (136 mg, 1.4 mmol), and toluene (4.3 mL). The crude product was purified using RP MPLC (MeOH / 0.1% NH3 in H2O; 10-100%) to yield 4-(4- phenylpiperidin-1-yl)-N-(quinoxalin-6-ylmethyl)pyridin-3-amine as a pale yellow solid (58 mg, 0.2 mmol, 31% yield).1H NMR (400 MHz, DMSO-d6) δ 8.90 (s, 2H), 8.09 (d, J = 8.6 Hz, 1H), 8.02 (s, 1H), 7.91 (d, J = 8.7 Hz, 1H), 7.79 (d, J = 5.0 Hz, 1H), 7.71 (s, 1H), 7.38 – 7.29 (m, 4H), 7.25 – 7.17 (m, 1H), 6.91 (d, J = 5.1 Hz, 1H), 5.79 (t, J = 6.0 Hz, 1H), 4.71 (d, J = 6.0 Hz, 2H), 3.43 (d, J = 11.6 Hz, 2H), 2.84 – 2.65 (m, 3H), 2.12 – 1.95 (m, 2H), 1.95 – 1.79 (m, 2H).13C NMR (101 MHz, DMSO-d6) δ 146.2, 145.70, 145.69, 145.2, 142.8, 142.2, 141.5, 139.2, 137.3, 132.5, 129.6, 129.2, 128.4, 126.7, 126.1, 126.0, 113.4, 50.5, 46.2, 41.6, 33.1. HRMS (ESI, m / z): calculated for C25H26N5[M+H]+: 396.21828; found 396.21744. Purity (LC): 97% Attorney Docket No.: 393976-00101 Example 19: Synthesis of 3-bromo-4- 1-yl)pyridine Prepared using the general procedure 1.1 using 3,4-dibromopyridine (500 mg, 2.1 mmol) and 4-benzylpiperidine (925 mg, 5.3 mmol) and acetonitrile (2.6 mL) The crude material was purified using NP MPLC (EtOAc / Hex; 0-100%) to provide 3-bromo-4-(4-benzylpiperidin-1- yl)pyridine as a white solid (446 mg, 1.4 mmol, 64% yield).1H NMR (400 MHz, DMSO-d6) δ 8.49 (s, 1H), 8.31 (d, J = 5.4 Hz, 1H), 7.35 – 7.26 (m, 2H), 7.25 – 7.15 (m, 3H), 7.02 (d, J = 5.5 Hz, 1H), 3.50 (d, J = 12.1 Hz, 2H), 2.71 – 2.62 (m, 2H), 2.58 (d, J = 6.7 Hz, 2H), 1.74 – 1.62 (m, 3H), 1.44 – 1.28 (m, 2H).13C NMR (101 MHz, DMSO-d6) δ 156.7, 152.3, 149.4, 140.1, 129.0, 128.1, 125.8, 115.87, 114.7, 50.26, 42.2, 36.9, 31.5. HRMS (ESI, m / z): calculated for C17H20N2Br [M+H]+: 331.08048; found 331.07959. Example 20: Synthesis of -N-(quinoxalin-6-ylmethyl)pyridin-3- amine Prepared using general procedure 1.2 using 4-(4-benzylpiperidin-1-yl)-3-bromopyridine (150 mg, 0.5 mmol), quinoxalin-6-ylmethanamine (144 mg, 1.0 mmol), Pd2dba3 (8 mg, 0.01 mmol) BINAP (11 mg, 0.02 mmol), NaOtBu (131 mg, 1.4 mmol), and toluene (4.1 mL). The crude product was purified using RP MPLC (MeOH / 0.1% NH3in H2O; 10-100%) to yield 4-(4- benzylpiperidin-1-yl)-N-(quinoxalin-6-ylmethyl)pyridin-3-amine as a yellow residue (27 mg, 0.08 mmol, 15% yield).1H NMR (400 MHz, DMSO-d6) δ 8.90(ABq, ∆υAB= 1.7 Hz, JAB= 1.9 Hz, Attorney Docket No.: 393976-00101 2H), 8.08 (d, J = 8.6 Hz, 1H), 8.00 (mc, 1H), 7.88 (dd, J = 8.7, 1.9 Hz, 1H), 7.75 (d, J = 5.1 Hz, 1H), 7.68 (s, J = 8.2 Hz, 1H), 7.36 – 7.25 (m, 2H), 7.25 – 7.15 (m, 3H), 6.84 (d, J = 5.1 Hz, 1H), 5.63 (t, J = 6.2 Hz, 1H), 4.68 (d, J = 6.1 Hz, 2H), 3.28 (m, 2H), 2.62 – 2.52 (m, 4H), 1.77 – 1.64 (m, 3H), 1.59 – 1.44 (m, 2H).13C NMR (101 MHz, DMSO-d6) δ 145.72, 145.70, 145.2, 142.8, 142.2, 141.5, 140.2, 139.2, 137.2, 132.4, 129.6, 129.2, 129.0, 128.2, 126.0, 125.8, 113.4, 50.0, 46.2, 42.5, 37.3, 31.8. HRMS (ESI, m / z): calculated for C26H28N5[M+H]+: 410.23388; found 410.23367. Purity (LC): 95% Example 21: Synthesis of tert- amino)pyridin-4-yl)piperazine- 1-carboxylate Prepared using general procedure 1.2 using tert-butyl 4-(3-bromopyridin-4-yl)piperazine- 1-carboxylate (200 mg, 0.6 mmol), quinolin-6-ylmethanamine (231 mg, 1.5 mmol), Pd2dba3(11 mg, 0.01 mmol) BINAP (15 mg, 0.02 mmol), NaOtBu (112 mg, 1.2 mmol), and toluene (5.3 mL). The crude product was purified NP MPLC (MeOH / DCM; 0-15%) to yield tert-butyl 4-(3- ((quinolin-7-ylmethyl)amino)pyridin-4-yl)piperazine-1-carboxylate as a yellow residue (231 mg, 0.6 mmol, 94% yield).1H NMR (400 MHz, DMSO-d6) δ 8.85 (dd, J = 4.2, 1.7 Hz, 1H), 8.33 (dd, J = 8.4, 1.2 Hz, 1H), 8.00 (d, J = 8.6 Hz, 1H), 7.91 (s, 1H), 7.82 – 7.75 (m, 2H), 7.71 (s, 1H), 7.50 (dd, J = 8.3, 4.2 Hz, 1H), 5.73 (t, J = 5.9 Hz, 1H), 4.61 (d, J = 5.9 Hz, 1H), 3.67 – 3.49 (m, 4H), 3.00 – 2.84 (m, 4H).13C NMR (101 MHz, CDCl3) δ 154.7, 150.4, 147.9, 145.8, 140.2, 138.1, 137.2, 136.0, 132.6, 130.2, 128.9, 128.3, 125.7, 121.5, 113.6, 80.2, 50.0, 48.2, 43.9 (broad), 28.5. HRMS (ESI, m / z): calculated for C24H30N5O2[M+H]+: 420.23938; found 420.23873.Rt = 1.74 (BASIC) Attorney Docket No.: 393976-00101 Example 22: Synthesis of 4-(piperazin-1-yl)-N-(quinolin-7-ylmethyl)pyridin-3-amine Prepared using general procedure 1.3 using tert-butyl 4-(3-((quinolin-7- ylmethyl)amino)pyridin-4-yl)piperazine-1-carboxylate (50 mg, 0.1 mmol) in DCM (2.4 mL) and TFA (0.2 mL, 3.0 mmol). The reaction was diluted with saturated NaHCO3 and extracted three times using EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated to yield 4-(piperazin-1-yl)-N-(quinolin-7-ylmethyl)pyridin-3-amine as a yellow residue (25 mg, 0.07 mmol, 66% yield).1H NMR (400 MHz, CD3OD) δ 8.77 (dd, J = 4.3, 1.7 Hz, 1H), 8.28 (dd, J = 8.4, 0.8 Hz, 1H), 7.99 (d, J = 8.7 Hz, 1H), 7.87 (d, J = 0.9 Hz, 1H), 7.81 – 7.76 (m, 2H), 7.68 (s, 1H), 7.48 (dd, J = 8.3, 4.3 Hz, 1H), 6.93 (d, J = 5.3 Hz, 1H), 4.63 (s, 2H), 3.03 (s, 8H).13C NMR (101 MHz, CD3OD) δ 150.9, 148.3, 148.2, 140.2, 140.0, 139.8, 138.2, 132.9, 130.5, 129.9, 129.5, 126.6, 122.8, 114.9, 51.6, 48.2, 46.5. HRMS (ESI, m / z): calculated for C19H22N5 [M+H]+: 320.18698; found 320.18685. Purity (LC): 98% Example 23: Synthesis of tert-butyl amino)pyridin-4-yl)piperazine-1- carboxylate Prepared using general procedure 1.2 using tert-butyl 4-(3-bromopyridin-4-yl)piperazine- 1-carboxylate (300 mg, 0.9 mmol), pyridin-2-ylmethanamine (237 mg, 2.2 mmol), Pd2dba3 (16 mg, 0.02 mmol) BINAP (22 mg, 0.04 mmol), NaOtBu (168 mg, 1.8 mmol), and toluene (8.0 mL). The crude product was purified NP MPLC (MeOH / DCM; 0-15%) followed by RP MPLC (MeOH / 0.1% NH3 in H2O; 10-100%) to yield tert-butyl 4-(3-((pyridin-2-ylmethyl)amino)pyridin- 4-yl)piperazine-1-carboxylate as a yellow residue (24 mg, 0.07 mmol, 8% yield).1H NMR (400 MHz, CD3OD) δ 8.55 – 8.52 (m, 1H), 7.82 (d, J = 5.2 Hz, 1H), 7.78 (td, J = 7.8, 1.9 Hz, 1H), 7.68 (s, 1H), 7.44 (d, J = 7.9 Hz, 1H), 7.30 (dd, J = 7.0, 5.5 Hz, 1H), 6.96 (d, J = 5.3 Hz, 1H), 4.53 (s, 2H), 3.70 – 3.60 (m, 4H), 3.04 – 2.95 (m, 4H), 1.49 (s, 9H).13C NMR (101 MHz, CD3OD) δ 159.9, 156.4, 145.0, 147.7, 140.2, 139.7, 138.8, 132.7, 123.8, 123.0, 115.1, 81.4, 50.8, 45.5 (broad), 28.7. HRMS (ESI, m / z): calculated for C20H28N5O2 [M+H]+: 370.22378; found 370.22348. Attorney Docket No.: 393976-00101 Example 24: Synthesis of -N-(pyridin-2-ylmethyl)pyridin-3-amine hydrochloride salt Prepared using general procedure 1.3 using tert-butyl 4-(3-((pyridin-2- ylmethyl)amino)pyridin-4-yl)piperazine-1-carboxylate (25 mg, 0.07 mmol) in DCM (0.7 mL) and 2 M HCl in Et2O (0.7 mL, 1.4 mmol) to yield 4-(piperazin-1-yl)-N-(pyridin-2-ylmethyl)pyridin- 3-amine hydrochloride as a light brown solid (17 mg, 0.06 mmol, 82% yield).1H NMR (400 MHz, CD3OD) δ 8.85 (d, J = 5.1 Hz, 1H), 8.58 (td, J = 7.9, 1.5 Hz, 1H), 8.18 (d, J = 6.3 Hz, 1H), 8.12 (d, J = 8.1 Hz, 1H), 8.04 – 7.98 (m, 2H), 7.53 (d, J = 6.4 Hz, 1H), 5.00 (s, 2H), 3.68 – 3.58 (m, 8H).13C NMR (101 MHz, CD3OD) δ 154.9, 153.8, 147.8, 143.6, 140.8, 134.2, 127.1, 126.9, 123.4, 116.6, 47.2, 46.1 44.3. HRMS (ESI, m / z): calculated for C15H20N5 [M+H]+: 270.17128; found 270.17098. Purity (LC): >99% Example 25: Synthesis of tert-butyl amino)pyridin-4-yl)piperazine-1- carboxylate Prepared using general procedure 1.2 using tert-butyl 4-(3-bromopyridin-4-yl)piperazine- 1-carboxylate (300 mg, 0.9 mmol), pyridin-3-ylmethanamine (237 mg, 2.2 mmol), Pd2dba3(16 mg, 0.02 mmol) BINAP (22 mg, 0.04 mmol), NaOtBu (168 mg, 1.8 mmol), and toluene (8.0 mL). The crude product was purified RP MPLC (MeOH / 0.1% NH3 in H2O; 10-100%) followed by NP MPLC (MeOH / DCM; 0-15%) to yield tert-butyl 4-(3-((pyridin-3-ylmethyl)amino)pyridin-4- yl)piperazine-1-carboxylate as a pale yellow residue (244 mg, 0.7 mmol, 75% yield).1H NMR (400 MHz, CD3OD) δ 8.56 (dd, J = 2.1, 0.7 Hz, 1H), 8.43 (dd, J = 4.9, 1.6 Hz, 1H), 7.87 – 7.84 (m, 1H), 7.82 (d, J = 5.3 Hz, 1H), 7.69 (s, 1H), 7.45 – 7.38 (m, 1H), 6.97 (d, J = 5.3 Hz, 1H), 4.54 Attorney Docket No.: 393976-00101 (s, 1H), 3.68 – 3.61 (m, 1H), 3.02 – 2.97 (m, 1H).13C NMR (101 MHz, CD3OD) δ 155.0, 147.6, 147.3, 146.5, 138.9, 138.0, 135.9, 135.6, 131.5, 123.9, 113.7, 80.0, 49.4, 44.2, 27.2. Piperazine C2 carbon was not observed. HRMS (ESI, m / z): calculated for C20H28N5O2[M+H]+: 370.22378; found 370.22374. Example 26: Synthesis of -N-(pyridin-3-ylmethyl)pyridin-3-amine hydrochloride salt Prepared using general procedure 1.3 using tert-butyl 4-(3-((pyridin-3- ylmethyl)amino)pyridin-4-yl)piperazine-1-carboxylate (30 mg, 0.08 mmol) in DCM (0.8 mL) and 2 M HCl in Et2O (0.8 mL, 1.6 mmol) to yield 4-(piperazin-1-yl)-N-(pyridin-3-ylmethyl)pyridin-3- amine hydrochloride as a brown residue (21 mg, 0.07 mmol, 85% yield).1H NMR (400 MHz, CD3OD) δ 8.99 (s, 1H), 8.82 (d, J = 5.5 Hz, 1H), 8.74 (d, J = 8.0 Hz, 1H), 8.16 – 8.07 (m, 2H), 7.92 (s, 1H), 7.50 (d, J = 6.3 Hz, 1H), 4.83 (s, 2H), 3.61 (app s, 8H).13C NMR (101 MHz, CD3OD) δ 153.6, 147.0, 141.9, 141.8, 140.7, 140.5, 133.7, 128.6, 123.2, 116.5, 47.0, 45.0, 44.3, 40.5. HRMS (ESI, m / z): calculated for C15H20N5[M+H]+: 270.17128; found 270.17096. Purity (LC): >99% Example 27: Synthesis of tert-butyl 4- 4-yl)piperazine-1-carboxylate Prepared using general procedure 2.1 using 4-chloro-3-nitropyridine (1.0 g, 6.3 mmol) and tert-butyl piperazine-1-carboxylate (2.4 g, 12.6 mmol) and acetonitrile (25.2 mL). The crude material was purified using NP MPLC (EtOAc / Hex; 0-100%) to provide tert-butyl 4-(3- nitropyridin-4-yl)piperazine-1-carboxylate (1.0 g, 3.3 mmol, 53% yield) as a yellow solid.1H NMR (400 MHz, DMSO-d6) δ 8.78 (s, 1H), 8.38 (d, J = 6.1 Hz, 1H), 7.92 (br s, 2H), 7.17 (d, J = Attorney Docket No.: 393976-00101 6.1 Hz, 1H), 3.53 – 3.41 (m, 4H), 3.24 (dd, J = 6.3, 4.2 Hz, 4H), 1.41 (s, 9H).13C NMR (101 MHz, DMSO-d6) δ 153.8, 152.4, 148.9, 147.6, 135.5, 113.1, 79.2, 48.5, 42.3 (broad), 28.0.HRMS (ESI, m / z): calculated for C14H21N4O4[M+H]+: 309.15578; found 309.15518. Example 28: Synthesis of tert-butyl 4- 4-yl)piperazine-1-carboxylate Prepared using general procedure 2.2 using tert-butyl 4-(3-nitropyridin-4-yl)piperazine-1- carboxylate (300 mg, 0.97 mmol) and 10 wt. % palladium on carbon (104 mg, 0.1 mmol) in methanol (9.7 mL) to provide tert-butyl 4-(3-aminopyridin-4-yl)piperazine-1-carboxylate (252 mg, 0.9 mmol, 93% yield) as a light yellow oil. The crude material was used in the next step without further purification.1H NMR (400 MHz, DMSO-d6) δ 7.89 (s, 1H), 7.69 (d, J = 5.2 Hz, 1H), 6.73 (d, J = 5.2 Hz, 1H), 4.79 (br s, 2H), 3.49 – 3.40 (m, 4H), 2.84 – 2.75 (m, 4H).13C NMR (101 MHz, DMSO-d6) δ 153.9, 143.5, 138.9, 137.9, 136.7, 113.3, 78.9, 48.6, 28.1. Piperazine C2 carbon was not observed. HRMS (ESI, m / z): calculated for C14H23N4O2[M+H]+: 279.18158; found 279.18069. Example 29: Synthesis of tert-butyl amino)pyridin-4-yl)piperazine- 1-carboxylate Prepared using general procedure 2.3 using tert-butyl 4-(3-aminopyridin-4-yl)piperazine- 1-carboxylate (157 mg, 0.56 mmol), pyrazine-2-carbaldehyde (73 mg, 0.68 mmol) and ethanol (5.6 mL) followed by addition of NaBH4 (64 mg, 1.7 mmol) and stirring for 3 hours. The crude material was purified using NP MPLC (0-10% MeOH / DCM) to provide tert-butyl 4-(3-((pyrazin- 2-ylmethyl)amino)pyridin-4-yl)piperazine-1-carboxylate (8.8 mg, 0.02 mmol, 4% yield) as a white solid. Physical state: off-white residue.1H NMR (400 MHz, CD3OD) δ 8.65 (d, J = 1.4 Hz, Attorney Docket No.: 393976-00101 1H), 8.61 (dd, J = 2.6, 1.6 Hz, 1H), 8.49 (d, J = 2.6 Hz, 1H), 7.84 (d, J = 5.2 Hz, 1H), 7.78 (s, 1H), 6.97 (d, J = 5.3 Hz, 1H), 4.62 (s, 2H), 3.65 (m, 5H), 3.02 – 2.97 (m, 5H), 1.49 (s, 9H).13C NMR (101 MHz, CD3OD) δ 155.0, 154.6, 146.5, 144.0, 143.3, 142.8, 139.1, 138.1, 131.3, 113.7, 80.0, 49.4, 46.0, 43.8, 27.2. Example 30: Synthesis of 4- 6-ylmethyl)pyridin-3-amine hydrochloride salt Prepared using general procedure 1.3 using tert-butyl 4-(3-((quinoxalin-6- ylmethyl)amino)pyridin-4-yl)piperazine-1-carboxylate (8.8 mg, 0.02 mmol) in DCM (0.42 mL) and 2 M HCl in Et2O (0.21 mL, 0.42 mmol). Concentrated under nitrogen to obtain 4-(piperazin- 1-yl)-N-(quinoxalin-6-ylmethyl)pyridin-3-amine (8.0 mg, 0.02 mmol, 97%) as a brown residue.1H NMR (400 MHz, CD3OD) δ 8.83 (s, 1H), 8.75 - 8.72 (m, 1H), 8.62 (d, J = 2.1 Hz, 1H), 8.10 (dd, J = 6.3, 1.0 Hz, 1H), 8.02 (d, J = 0.9 Hz, 1H), 7.48 (d, J = 6.3 Hz, 1H), 4.78 (s, 2H), 3.60 - 3.57 (m, 8H).13C NMR (101 MHz, CD3OD) δ 155.5, 153.1, 146.2, 143.8, 143.3, 141.2, 132.9, 123.2, 116.2, 116.0, 47.0, 46.9, 44.3. Purity (LC): 91% Example 31: Synthesis of tert- 6-ylamino)pyridin-4-yl)piperazine-1- carboxylate Prepared using general procedure 1.2 using tert-butyl 4-(3-bromopyridin-4-yl)piperazine- 1-carboxylate (500 mg, 1.5 mmol), quinoxalin-6-ylmethanamine (233 mg, 1.6 mmol), Pd2dba3(53 mg, 0.3 mmol) BINAP (91 mg, 0.6 mmol), NaOtBu (421 mg, 4.4 mmol), and toluene (13 mL). The crude product was purified using NP MPLC (MeOH / DCM; 0-10%) then RP MPLC Attorney Docket No.: 393976-00101 (MeOH / 0.1% NH3 in H2O; 10-100%) to provide tert-butyl 4-(3-(quinoxalin-6-ylamino)pyridin-4- yl)piperazine-1-carboxylate as a yellow-brown solid (284 mg, 0.7 mmol, 48% yield).1H NMR (400 MHz, DMSO-d6) δ 8.69 (d, J = 1.9 Hz, 1H), 8.59 (d, J = 1.9 Hz, 1H), 8.55 (s, 1H), 8.34 (s, 1H), 8.23 (d, J = 5.5 Hz, 1H), 7.89 (d, J = 9.1 Hz, 1H), 7.47 (dd, J = 9.1, 2.6 Hz, 1H), 7.00 (d, J = 5.5 Hz, 1H), 6.93 (d, J = 2.5 Hz, 1H), 3.13 – 3.03 (m, 8H), 1.33 (s, 9H).13C NMR (101 MHz, CD3OD) δ 156.1, 153.4, 147.3, 147.2, 146.7, 146.3, 145.4, 142.4, 139.5, 130.4, 124.5, 114.8, 108.9, 81.4, 49.2, 44.4. HRMS (ESI, m / z): calculated for C22H27N6O2[M+H]+: 407.21898; found 407.21832. Example 32: Synthesis of 6-ylmethyl)pyridin-3-amine hydrochloride salt Prepared using general procedure 1.3 using tert-butyl 4-(3-(quinoxalin-6-ylamino)pyridin- 4-yl)piperazine-1-carboxylate (100 mg, 0.3 mmol) in DCM (12 mL) and 2 M HCl in Et2O (1.2 mL, 2.5 mmol). Concentrated under nitrogen to obtain 4-(piperazin-1-yl)-N-(quinoxalin-6- ylmethyl)pyridin-3-amine hydrochloride salt as an orange solid (94 mg, 0.03 mmol, 100% yield).1H NMR (400 MHz, DMSO-d6) δ 9.39 ( br s, 1H), 9.32 (s, 1H), 8.79 (d, J = 2.0 Hz, 1H), 8.70 (d, J = 2.0 Hz, 1H), 8.53 (s, 1H), 8.42 (d, J = 6.9 Hz, 1H), 8.00 (d, J = 9.1 Hz, 1H), 7.60 (dd, J = 9.1, 2.6 Hz, 1H), 7.50 (d, J = 6.9 Hz, 1H), 7.07 (d, J = 2.5 Hz, 1H), 3.82 – 3.67 (m, 4H), 2.95 (s, 4H).13C NMR (101 MHz, DMSO-d6) δ 155.6, 145.0, 144.6, 142.7, 142.5, 138.9, 137.3, 137.1, 130.5, 128.1, 123.8, 114.6, 107.6, 44.63, 42.3. HRMS (ESI, m / z): calculated for C17H19N6[M+H]+: 307.16658; found 307.16608. Purity (LC): >99% Example 33: Synthesis of N-(4- quinoxalin-6-amine Attorney Docket No.: 393976-00101 Prepared using general procedure 1.2 using 4-(3-bromopyridin-4-yl)morpholine (370 mg, 1.5 mmol), quinoxalin-6-ylmethanamine (243 mg, 1.7 mmol), Pd2dba3 (56 mg, 0.06 mmol) BINAP (95 mg, 0.15 mmol), NaOtBu (439 mg, 4.6 mmol), and toluene (13.8 mL). The crude product was purified using NP MPLC (MeOH / DCM; 0-10%) then RP MPLC (MeOH / 0.1% NH3 in H2O; 10- 100%) to provide N-(4-morpholinopyridin-3-yl)quinoxalin-6-amine as a yellow solid (328 mg, 1.1 mmol, 70% yield).1H NMR (400 MHz, DMSO-d6) δ 8.68 (d, J = 1.9 Hz, 1H), 8.57 (d, J = 1.9 Hz, 1H), 8.55 (s, 1H), 8.30 (s, 1H), 8.21 (d, J = 5.5 Hz, 1H), 7.87 (d, J = 9.1 Hz, 1H), 7.44 (dd, J = 9.1, 2.6 Hz, 1H), 6.97 (d, J = 5.5 Hz, 1H), 6.89 (d, J = 2.5 Hz, 1H), 3.34 – 3.32 (m, 4H), 3.11 – 3.05 (m, 4H).13C NMR (101 MHz, DMSO-d6) δ 150.7, 146.9, 146.5, 145.4, 145.1, 144.1, 141.23, 137.6, 129.4, 127.9, 122.7, 112.9, 107.4, 65.7, 48.2. HRMS (ESI, m / z): calculated for C17H18N5O [M+H]+: 308.15058; found 308.14990. Purity: >99% (LC) Example 34: Synthesis of tert-butyl (1- 4-yl)piperidin-4-yl)carbamate Prepared using general procedure 1.1 using 3,4-dibromopyridine (200 mg, 0.8 mmol), tert- butyl piperidin-4-ylcarbamate (338 mg, 2 Eq, 1.7 mmol), in acetonitrile (0.8 mL,). The crude material was purified using NP MPLC (EtOAc / Hex; 0-100%) to provide tert-butyl (1-(3- bromopyridin-4-yl)piperidin-4-yl)carbamate as a white residue (170 mg, 0.4 mmol, 55% yield).1H NMR (400 MHz, CDCl3) δ 8.55 (s, 1H), 8.33 (d, J = 5.4 Hz, 1H), 6.84 (d, J = 5.4 Hz, 1H), 4.54 – 4.46 (m, 1H), 3.70 – 3.61 (m, 1H), 3.57 – 3.50 (m, 2H), 2.89 – 2.79 (m, 2H), 2.12 – 2.04 (m, 2H), 1.67 – 1.56 (m, 2H), 1.46 (s, 9H).13C NMR (101 MHz, CD3OD) δ 157.8, 156.4, 151.9, 151.9, 148.4, 115.4, 114.7, 78.6, 49.2, 47.3, 31.68, 27.37. HRMS (ESI, m / z): calculated for C15H23N3O2Br [M+H]+: 356.09682; found 356.09753. Attorney Docket No.: 393976-00101 Example 35: Synthesis of tert-butyl (1-(3-((quinoxalin-6-ylmethyl)amino)pyridin-4- yl)piperidin-4-yl)carbamate Prepared using general procedure 1.2 using tert-butyl (1-(3-bromopyridin-4-yl)piperidin- 4-yl)carbamate (137 mg, 0.4 mmol), quinoxalin-6-ylmethanamine (122 mg, 0.8 mmol), Pd2dba3 (352 mg, 0.4 mmol), BINAP (23.9 mg, 0.04 mmol), NaOtBu (111 mg, 1.2 mmol), and toluene (0.07 mL). The crude material was purified using RP MPLC (MeOH / 0.1% NH3in H2O; 10-100%) to provide tert-butyl (1-(3-((quinoxalin-6-ylmethyl)amino)pyridin-4-yl)piperidin-4-yl)carbamate as a yellow amorphous solid (74.0 mg, 0.2 mmol, 44% yield).1H NMR (400 MHz, CD3OD) δ 8.45 (s, 1H), 8.26 (d, J = 5.6 Hz, 1H), 7.05 (d, J = 5.6 Hz, 1H), 3.64 – 3.56 (m, 2H), 3.53 (dd, J = 10.1, 4.3 Hz, 1H), 2.94 – 2.82 (m, 2H), 1.98 (ddd, J = 16.2, 5.9, 2.7 Hz, 2H), 1.65 (ddd, J = 12.8, 11.1, 3.8 Hz, 2H), 1.45 (s, 9H).13C NMR (100 MHz, CD3OD) δ 156.7, 147.3, 144.8, 142.9, 142.6, 141.9, 138.9, 138.2, 131.3, 129.6, 129.0, 125.6, 113.7, 108.0, 49.0, 46.6, 32.2, 27.4. HRMS (ESI, m / z): calculated for C25H32N5O2 [M+H]+: 435.25030; found 434.25513. Example 36: Synthesis of 4- -N-(quinoxalin-6-ylmethyl)pyridin-3- amine Prepared using general procedure 1.3 using tert-butyl (1-(3-((quinoxalin-6- ylmethyl)amino)pyridin-4-yl)piperidin-4-yl)carbamate (73.9 mg, 0.2 mmol), 2 M HCl in Et2O (0.9 mL, 1.7 mmol), and dichloromethane (8.5 mL) overnight. The crude material was purified using RP MPLC (MeOH / 0.1% NH3 in H2O; 10-100%) to provide 4-(4-aminopiperidin-1-yl)-N- (quinoxalin-6-ylmethyl)pyridin-3-amine as a yellow residue (23 mg, 0.08 mmol, 40% yield).1H NMR (400 MHz, CD3OD) δ 8.85 (ABq, ∆^^^^= 2.98 Hz, JAB = 2.0 Hz, 2H), 8.10 (d, J = 8.7 Hz, 1H), 8.04 (br s, 1H), 7.91 (dd, J = 8.8, 1.9 Hz, 1H), 7.79 (d, J = 5.2 Hz, 1H), 7.66 (s, 1H), 6.98 (d, J = 5.3 Hz, 1H), 4.73 (s, 2H), 3.47 – 3.39 (m, 2H), 2.93 – 2.83 (m, 1H), 2.80 – 2.70 (m, 2H), 2.04 – 1.97 (m, 2H), 1.73 – 1.60 (m, 2H).13C NMR (101 MHz, CD3OD) δ 147.3, 145.2, 144.8, 142.9, Attorney Docket No.: 393976-00101 142.6, 141.9, 138.9, 138.2, 131.3, 129.6, 129.0, 125.7, 113.7, 48.9, 46.7, 34.3. HRMS (ESI, m / z): calculated for C19H23N6 [M+H]+: 335.19787; found 335.19776. Purity (LC): 96% Example 37: Synthesis of tert-butyl ((1- 4-yl)piperidin-4-yl)methyl)carbamate Prepared using the general procedure 1.1 using 3,4-dibromopyridine (500 mg, 2.1 mmol) and tert-butyl (piperidin-4-ylmethyl)carbamate (905 mg, 4.2 mmol) and acetonitrile (2.6 mL) The crude material was purified using RP MPLC (MeOH / 0.1% NH3in H2O; 10-100%) and then NP MPLC (EtOAc / Hex; 0-100%) to provide tert-butyl ((1-(3-bromopyridin-4-yl)piperidin-4- yl)methyl)carbamate as a white solid (503 mg, 1.4 mmol, 65% yield).1H NMR (400 MHz, DMSO- d6) δ 8.50 (s, 1H), 8.32 (d, J = 5.4 Hz, 1H), 7.04 (d, J = 5.5 Hz, 1H), 6.90 (t, J = 5.6 Hz, 1H), 3.50 (d, J = 12.0 Hz, 2H), 2.88 (t, J = 6.3 Hz, 2H), 2.68 (app t, J = 11.2 Hz, 2H), 1.73 (app d, J = 11.5 Hz, 2H), 1.62 – 1.46 (m, 1H), 1.38 (s, 9H), 1.33 – 1.17 (m, 2H).13C NMR (101 MHz, DMSO-d6) δ 156.7, 155.7, 152.3, 149.4, 115.8, 114.7, 77.4, 50.1, 45.3, 35.7, 29.4, 28.3.HRMS (ESI, m / z): calculated for C16H25N3O2Br [M+H]+: 370.11248; found 370.11221. Example 38: Synthesis 6-ylmethyl)amino)pyridin-4- yl)piperidin-4-yl)methyl)carbamate Prepared using general procedure 1.2 using (tert-butyl ((1-(3-bromopyridin-4-yl)piperidin- 4-yl)methyl)carbamate (125 mg, 0.3 mmol), quinoxalin-6-ylmethanamine (107 mg, 0.7 mmol), Pd2dba3 (6 mg, 0.07 mmol) BINAP (8 mg, 0.14 mmol), NaOtBu (65 mg, 0.7 mmol), and toluene (3 mL). The crude product was purified using NP MPLC (MeOH / DCM; 0-10%) followed by RP MPLC (MeOH / 0.1% NH3in H2O; 10-100%) to yield tert-butyl ((1-(3-((quinoxalin-6- Attorney Docket No.: 393976-00101 ylmethyl)amino)pyridin-4-yl)piperidin-4-yl)methyl)carbamate as a yellow residue (35 mg, 0.007 mmol, 23% yield).1H NMR (400 MHz, CD3OD) δ 8.86 – 8.83 (m, 2H), 8.09 (d, J = 8.7 Hz, 1H), 8.04 (s, 1H), 7.90 (dd, J = 8.7, 1.7 Hz, 1H), 7.79 (d, J = 5.1 Hz, 1H), 7.65 (s, 1H), 6.97 (d, J = 5.3 Hz, 1H), 4.72 (s, 2H), 3.45 (d, J = 11.8 Hz, 2H), 2.67 (t, J = 11.1 Hz, 2H), 1.86 (d, J = 11.4 Hz, 2H), 1.72 – 1.60 (m, 1H), 1.56 – 1.46 (m, 2H), 1.44 (s, 9H).13C NMR (101 MHz, CD3OD) δ 158.7, 149.1, 146.6, 146.2, 144.3, 144.0, 143.3, 140.3, 139.7, 132.6, 131.1, 130.3, 127.1, 115.1, 79.9, 51.5, 48.1, 47.0, 37.9, 31.2, 28.8. HRMS (ESI, m / z): calculated for C25H33N6O2[M+H]+: 449.26598; found 449.26525. Example 39: Synthesis piperidin-1-yl)-N-(quinoxalin-6- ylmethyl)pyridin-3-amine hydrochloride salt Prepared using general procedure 1.3 using tert-butyl 4-(3-(quinoxalin-6-ylamino)pyridin- 4-yl)piperazine-1-carboxylate (10 mg, 0.02 mmol) in DCM (0.5 mL) and 2 M HCl in Et2O (0.2 mL, 0.5 mmol). Concentrated under nitrogen to obtain 4-(4-(aminomethyl)piperidin-1-yl)-N- (quinoxalin-6-ylmethyl)pyridin-3-amine hydrochloride salt as a gray solid (8.8 mg, 0.02 mmol, 100% yield).1H NMR (400 MHz, DMSO-d6) δ 14.61 (br s, 1H), 8.93 (s, 1H), 8.18 (br s, 2H), 8.11 (d, J = 8.7 Hz, 1H), 8.05 – 8.01 (m, 2H), 7.90 (dd, J = 8.6, 1.8 Hz, 1H), 7.72 (s, 1H), 7.29 (d, J = 6.4 Hz, 1H), 6.46 (t, J = 5.5 Hz, 1H), 4.74 (d, J = 5.6 Hz, 2H), 3.74 (d, J = 12.5 Hz, 2H), 2.87 (t, J = 11.5 Hz, 2H), 2.82 – 2.70 (m, 2H), 1.90 (dd, J = 23.2, 12.2 Hz, 3H), 1.58 – 1.49 (m, 2H).13C NMR (101 MHz, CD3OD) δ 149.1, 146.6, 146.2, 144.4, 144.0, 143.3, 140.3, 139.7, 132.7, 131.1, 130.4, 127.0, 115.1, 51.6, 48.3, 48.1, 39.5, 31.3. HRMS (ESI, m / z): calculated for C20H25N6 [M+H]+: 349.21348 ; found 349.21274. Purity (LC): 96% Attorney Docket No.: 393976-00101 Example 40: Synthesis of tert-butyl -1-carboxylate Prepared using general procedure 1.1 using 3,4-dibromopyridine (500 mg, 2.1 mmol), tert- butyl [4,4'-bipiperidine]-1-carboxylate (1.0 g, 3.7 mmol), and acetonitrile (2.6 mL). The crude material was purified using NP MPLC (EtOAc / Hex; 5-100%) to provide tert-butyl [4,4'- bipiperidine]-1-carboxylate as a white solid (443 mg, 1.0 mmol, 47% yield).1H NMR (400 MHz, DMSO-d6) δ 8.47 (app s, 2H), 8.30 (d, J = 5.4 Hz, 1H), 7.01 (d, J = 5.5 Hz, 1H), 3.95 (d, J = 12.7 Hz, 2H), 3.53 (d, J = 12.0 Hz, 2H), 2.64 (t, J = 11.4 Hz, 4H), 1.75 (d, J = 10.8 Hz, 2H), 1.66 (d, J = 12.3 Hz, 2H), 1.34 – 1.16 (m, 4H), 1.10 – 0.93 (m, 2H).13C NMR (101 MHz, DMSO-d6) δ 156.6, 153.8, 152.3, 149.4, 115.7, 114.6, 78.4, 50.5, 43.6 (broad), 40.2, 39.7, 28.82, 28.77, 28.1. Example 41: Synthesis of tert- 6-ylmethyl)amino)pyridin-4-yl)-[4,4'- bipiperidine]-1-carboxylate Prepared using general procedure 1.2 tert-butyl 1'-(3-bromopyridin-4-yl)-[4,4'- bipiperidine]-1-carboxylate (422 mg, 1.0 mmol), quinoxalin-6-ylmethanamine (421 mg, 2.6 mmol), Pd2dba3 (18 mg, 0.02 mmol) BINAP (25 mg, 0.04 mmol), NaOtBu (191 mg, 2.0 mmol), and toluene (9 mL). The crude product was purified by NP MPLC (MeOH / DCM; 0-10%) to yield tert-butyl 1'-(3-((quinoxalin-6-ylmethyl)amino)pyridin-4-yl)-[4,4'-bipiperidine]-1-carboxylate as a dark orange residue (107 mg, 0.2 mmol, 21% yield).1H NMR (400 MHz, CDCl3) δ 8.84 (ABq, Attorney Docket No.: 393976-00101 ∆υAB = 3.2 Hz, JAB = 1.9 Hz, 2H), 8.13 (d, J = 8.6 Hz, 1H), 8.04 (d, J = 1.1 Hz, 1H), 7.97 (d, J = 5.5 Hz, 1H), 7.80 (s, J = 4.7 Hz, 1H), 7.77 (dd, J = 8.7, 1.9 Hz, 1H), 6.91 (d, J = 5.5 Hz, 1H), 4.74 (t, J = 5.7 Hz, 1H), 4.65 (d, J = 5.5 Hz, 2H), 4.19 – 4.05 (m, 2H), 3.53 – 3.43 (m, 2H), 2.73 – 2.55 (m, 4H), 1.87 (d, J = 12.1 Hz, 2H), 1.69 (d, J = 12.4 Hz, 2H), 1.44 (s, 9H), 1.42 – 1.10 (m, 6H).13C NMR (100 MHz, CDCl3) δ 155.0, 148.8, 145.4, 145.1, 143.3, 142.7, 140.8, 138.3, 137.9, 130.4, 129.4, 129.1, 126.9, 113.7, 79.5, 50.9, 48.1, 44.2, 41.1, 40.8, 29.5, 29.4, 28.6. Example 42: Synthesis of 4-([4,4'- 6-ylmethyl)pyridin-3-amine Prepared using general procedure 1.3 tert-butyl 1'-(3-((quinoxalin-6- ylmethyl)amino)pyridin-4-yl)-[4,4'-bipiperidine]-1-carboxylate (20 mg, 0.04 mmol) in DCM (2. mL) and 2M HCl in Et2O (0.4 mL, 0.8 mmol). The crude product was purified RP MPLC (MeOH / 0.1% NH3 in H2O; 10-100%) to yield 4-([4,4'-bipiperidin]-1-yl)-N-(quinoxalin-6- ylmethyl)pyridin-3-amine as a yellow residue (7 mg, 0.02 mmol, 41% yield).1H NMR (400 MHz, CD3OD) δ 8.85 (ABq, ∆υAB = 2.5 Hz, JAB = 1.9 Hz, 2H), 8.09 (d, J = 8.7 Hz, 1H), 8.04 (d, J = 1.0 Hz, 1H), 7.90 (dd, J = 8.7, 1.8 Hz, 1H), 7.78 (d, J = 5.3 Hz, 1H), 7.65 (s, 1H), 6.96 (d, J = 5.3 Hz, 1H), 4.73 (s, 2H), 3.48 (app d, J = 11.8 Hz, 2H), 3.11 (app d, J = 12.5 Hz, 2H), 2.63 (app q, J = 12.0 Hz, 4H), 1.90 (app d, J = 12.4 Hz, 2H), 1.81 (app d, J = 12.0 Hz, 2H), 1.61 – 1.47 (m, 2H), 1.38 – 1.21 (m, 4H).13C NMR (101 MHz, DMSO-d6) δ 155.3, 155.2, 154.7, 152.3, 151.7, 151.0, 148.7, 146.6, 141.9, 139.1, 138.7, 135.5, 122.8, 59.9, 56.0, 55.7, 50.7, 50.3, 38.48, 38.45. Purity (LC): 95% Attorney Docket No.: 393976-00101 Example 43: Synthesis of 1-(3-bromopyridin-4-yl)-4-methylpiperazine Prepared using the general procedure 1.1 using 3,4-dibromopyridine (2.0 g, 8.4 mmol), 1- methylpiperazine (2.34 mL, 21.1 mmol), and acetonitrile (10.6 mL). The crude material was purified using RP MPLC (MeOH / 0.1% NH3 in H2O; 10-100%) to provide 1-(3-bromopyridin-4- yl)-4-methylpiperazine as a brown oil (955 mg, 3.7 mmol, 44% yield).1H NMR (400 MHz, CDCl3) δ 8.55 (s, 1H), 8.34 (d, J = 5.4 Hz, 1H), 6.85 (d, J = 5.4 Hz, 1H), 3.28 – 3.20 (m, 4H), 2.67 – 2.58 (m, 5H), 2.38 (s, 3H).13C NMR (101 MHz, CDCl3) δ 156.7, 153.4, 149.5, 115.4, 115.3, 54.9, 50.1, 46.1. HRMS (ESI, m / z): calculated for C10H15N3Br [M+H]+: 256.04438; found 256.04388. Example 44: Synthesis of 4- -N-(quinoxalin-6-ylmethyl)pyridin-3- amine Prepared using general procedure 1.2 using 1-(3-bromopyridin-4-yl)-4-methylpiperazine (200 mg, 0.8 mmol), quinoxalin-6-ylmethanamine (249 mg, 1.6 mmol), Pd2dba3 (14 mg, 0.02 mmol) BINAP (48 mg, 0.08 mmol), NaOtBu (225 mg, 2.4 mmol), and toluene (7.1 mL). The crude product was purified using RP MPLC (MeOH / 0.1% NH3in H2O; 10-100%) followed by RP MPLC (MeCN / 0.1% NH3 in H2O; 10-100%) to yield 4-(4-methylpiperazin-1-yl)-N-(quinoxalin- 6-ylmethyl)pyridin-3-amine as an orange residue (156 mg, 1.0 mmol, 60% yield).1H NMR (400 MHz, CD3OD) δ 8.83 (s, 2H), 8.07 (d, J = 8.7 Hz, 1H), 8.01 (s, 1H), 7.88 (d, J = 8.8 Hz, 1H), 7.80 (d, J = 5.3 Hz, 1H), 7.68 (s, 1H), 6.98 (d, J = 5.3 Hz, 1H), 4.72 (s, 2H), 3.13 (br s, 4H), 2.71 (br s, 4H), 2.37 (s, 3H).13C NMR (101 MHz, CD3OD) δ 147.9, 146.6, 146.2, 144.2, 143.9, 143.3, 140.4, 139.5, 133.0, 131.0, 130.4, 127.0, 115.0, 56.0, 50.4, 48.0, 46.1. HRMS (ESI, m / z): calculated for C19H23N6 [M+H]+: 335.19788; found 335.19708. Purity (LC): 99% Attorney Docket No.: 393976-00101 Example 45: Synthesis of tert-butyl 9- 4-yl)-3,9-diazaspiro[5.5]undecane-3- carboxylate Prepared using general procedure 1.1 using tert-butyl 3,9-diazaspiro[5.5]undecane-3- carboxylate (300 mg, 1.2 mmol), 3,4-dibromopyridine (140 mg, 0.6 mmol), and acetonitrile (0.6 mL). The crude material was purified using NP MPLC (EtOAc / Hex; 0-100%) to yield tert-butyl 9-(3-bromopyridin-4-yl)-3,9-diazaspiro[5.5]undecane-3-carboxylate as a white amorphous solid (133 mg, 0.7 mmol, 55% yield).1H NMR (400 MHz, CD3OD) δ 8.44 (s, 1H), 8.25 (d, J = 5.6 Hz, 1H), 7.06 (d, J = 5.6 Hz, 1H), 3.48 – 3.40 (m, 4H), 3.26 – 3.19 (m, 4H), 1.75 – 1.68 (m, 4H), 1.57 – 1.50 (m, 4H), 1.45 (s, 9H).13C NMR (101 MHz, CD3OD) δ 158.0, 151.9, 148.3, 115.2, 79.5, 45.7, 34.9, 29.3, 27.3. HRMS (ESI, m / z): calculated for C19H29N3O2Br [M+H]+: 410.14377; found 410.14388. Example 46: Synthesis of 6-ylmethyl)amino)pyridin-4-yl)-3,9- diazaspiro[5.5]undecane-3-carboxylate Prepared using general procedure 1.2 using tert-butyl 9-(3-bromopyridin-4-yl)-3,9- diazaspiro[5.5]undecane-3-carboxylate (133 mg, 0.3 mmol), quinoxalin-6-ylmethanamine (103 mg, 0.6 mmol), Pd2dba3(11.9 mg, 0.01 mmol), BINAP (20.2 mg, 0.03 mmol), NaOtBu (93.4 mg, 1.0 mmol), and toluene (3.0 mL). The crude material was purified with RP MPLC (MeOH / 0.1% NH3 in H2O; 10-100%) to yield tert-butyl 9-(3-((quinoxalin-6-ylmethyl)amino)pyridin-4-yl)-3,9- diazaspiro[5.5]undecane-3-carboxylate as a yellow residue (50 mg, 0.1 mmol, 32% yield).1H Attorney Docket No.: 393976-00101 NMR (400 MHz, CD3OD) δ 8.87 – 8.80 (m, 2H), 8.08 (d, J = 8.7 Hz, 1H), 8.05 – 8.00 (m, 1H), 7.89 (dd, J = 8.8, 2.0 Hz, 1H), 7.81 – 7.77 (m, 1H), 7.67 – 7.63 (m, 1H), 7.00 (d, J = 5.2 Hz, 1H), 4.72 (s, 2H), 3.48 – 3.42 (m, 4H), 3.34 (s, 49H), 3.10 – 3.03 (m, 4H), 1.80 – 1.73 (m, 4H), 1.58 – 1.51 (m, 4H), 1.46 (s, 10H).13C NMR (101 MHz, CD3OD) δ 155.3, 147.7, 145.2, 144.8, 142.9, 142.6, 141.9, 138.8, 131.1, 129.6, 128.9, 125.6, 113.6, 79.5, 48.4, 46.6, 45.5, 35.2, 29.5, 27.3. HRMS (ESI, m / z): calculated for C28H37N6O2[M+H]+: 489.29724; found 489.29741. Example 47: Synthesis of -4-(3,9-diazaspiro[5.5]undecan-3- yl)pyridin-3-amine Prepared using general procedure 1.3 using 9-(3-((quinoxalin-6-ylmethyl)amino)pyridin- 4-yl)-3,9-diazaspiro[5.5]undecane-3-carboxylate (25 mg, 0.05 mmol) and 2 M HCl in Et2O (0.26 mL, 0.5 mmol). The crude material was purified using RP MPLC (MeOH / 0.1% NH3 in H2O; 10- 100%) to yield the product N-(quinoxalin-6-ylmethyl)-4-(3,9-diazaspiro[5.5]undecan-3- yl)pyridin-3-amine as a yellow residue (20 mg, 0.05 mmol, quant.).1H NMR (400 MHz, CD3OD) δ 8.82 (ABq, ∆^^^^= 2.40 Hz, JAB= 2.08 Hz, 2H), 8.07 (d, J = 8.7 Hz, 1H), 8.01 (s, 1H), 7.88 (dd, J = 8.8, 1.9 Hz, 1H), 7.76 (d, J = 5.3 Hz, 1H), 7.63 (s, 1H), 6.97 (d, J = 5.4 Hz, 1H), 4.70 (s, 2H), 3.08 – 2.98 (m, 4H), 2.87 – 2.77 (m, 4H), 1.81 – 1.70 (m, 4H), 1.64 – 1.50 (m, 4H).13C NMR (101 MHz, CDCl3) δ 146.2, 145.2, 144.8, 143.2, 142.5, 141.6, 140.7, 137.7, 132.9, 130.0, 129.4, 126.8, 113.4, 47.9, 45.9, 40.6, 36.04, 36.04, 29.5. HRMS (ESI, m / z): calculated for C23H29N6[M+H]+: 389.244816; found 389.24495. Purity (LC): >99% Attorney Docket No.: 393976-00101 Example 48: Synthesis of tert-butyl (2-(4-(3-((quinoxalin-6-ylmethyl)amino)pyridin-4- yl)piperazin-1-yl)ethyl)carbamate To a round bottom flask containing 4-(piperazin-1-yl)-N-(quinoxalin-6-ylmethyl)pyridin- 3-amine (60 mg, 0.2 mmol) was added a stir bar, acetone (1.0 mL) and potassium carbonate (52 mg, 0.4 mmol) followed by tert-butyl (2-bromoethyl)carbamate (84 mg, 0.4 mmol). Let stir at 30 °C for 16 hours. The stir bar was removed and contents were dried under nitrogen and purified using RP MPLC (MeOH / 0.1% NH3in H2O; 10-100%) to yield tert-butyl (2-(4-(3-((quinoxalin-6- ylmethyl)amino)pyridin-4-yl)piperazin-1-yl)ethyl)carbamate as a yellow residue (5.7 mg, 0.01 mmol, 7% yield).1H NMR (400 MHz, CD3OD) δ 8.85 (ABq, ∆υAB= 2.3 Hz, JAB= 2.0 Hz, 2H), 8.09 (d, J = 8.7 Hz, 1H), 8.03 (s, 1H), 7.90 (dd, J = 8.7, 1.9 Hz, 1H), 7.81 (d, J = 5.3 Hz, 1H), 7.67 (s, 1H), 6.99 (d, J = 5.3 Hz, 1H), 4.73 (s, 2H), 3.26 (t, J = 6.7 Hz, 2H), 3.14 (s, 4H), 2.77 (s, 4H), 2.57 (t, J = 6.8 Hz, 2H), 1.45 (s, 9H).13C NMR (101 MHz, CD3OD) δ 158.4, 148.1, 146.6, 146.2, 144.3, 144.0, 143.3, 140.4, 139.5, 132.9, 131.0, 130.4, 127.1, 114.9, 80.1, 58.8, 54.3, 50.58, 38.4, 28.8. HRMS (ESI, m / z): calculated for C25H34N7O2[M+H]+: 464.27688; found 464.27666. Example 49: Synthesis piperazin-1-yl)-N-(quinoxalin-6- ylmethyl)pyridin-3-amine hydrochloride salt Prepared using general procedure 1.3 using tert-butyl (2-(4-(3-((quinoxalin-6- ylmethyl)amino)pyridin-4-yl)piperazin-1-yl)ethyl)carbamate (6.0 mg, 0.01 mmol) in DCM (0.03 mL) and 2 M HCl in Et2O (0.03 mL, 0.5 mmol) to provide 4-(4-(2-aminoethyl)piperazin-1-yl)- N-(quinoxalin-6-ylmethyl)pyridin-3-amine hydrochloride salt as a brown residue (6 mg, 0.01 mmol, quant.).1H NMR (400 MHz, CD3OD) δ 8.89 (m, 2H), 8.14 (d, J = 8.7 Hz, 1H), 8.08 (d, J = 1.2 Hz, 1H), 8.06 (dd, J = 6.3, 1.1 Hz, 1H), 7.97 (dd, J = 8.7, 1.9 Hz, 1H), 7.80 (d, J = 1.1 Hz, 1H), 7.49 (d, J = 6.3 Hz, 1H), 3.82 (br s, 4H), 3.66 – 3.62 (m, 2H), 3.60 – 3.55 (m, 2H). Benzylic 2H below water peak at 4.87.13C NMR (101 MHz, CD3OD) δ 152.8, 146.7, 146.5, 143.8, 143.4, Attorney Docket No.: 393976-00101 142.0, 141.2, 132.8, 131.1, 130.7, 127.3, 123.2, 116.4, 54.7, 53.1, 47.6, 46.9, 35.1. HRMS (ESI, m / z): calculated for C20H26N7 [M+H]+: 364.22438; found 364.22413. Purity (LC): 97% Example 50: Synthesis of 1-(3- -N,N-dimethylpiperidin-4-amine To a vial was added 1-(3- piperidin-4-amine (63 mg, 0.3 mmol), 38% Wt., formaldehyde (43 mg, 0.04 mL, 0.5 mmol), and formic acid (0.05 mL, 1.2 mmol). The reaction was stirred at 85 °C for 6 h. Once cooled, 1M HCl was added until pH = 2 and then contents of the flask were removed in vacuo. The crude mixture was dissolved in water and 1M NaOH was added until pH = 10. The aqueous layer was extracted with DCM and concentrated. The crude material was purified using RP MPLC (MeOH / 0.1% NH3in H2O; 10-100%) to yield 1- (3-bromopyridin-4-yl)-N,N-dimethylpiperidin-4-amine as a clear residue (28 mg, 0.1 mmol, 40% yield).1H NMR (400 MHz, CDCl3) δ 8.53 (s, 1H), 8.30 (d, J = 5.4 Hz, 1H), 6.82 (d, J = 5.4 Hz, 1H), 3.69 – 3.59 (m, 2H), 2.72 (td, J = 12.1, 2.3 Hz, 2H), 2.33 (s, 6H), 1.97 – 1.89 (m, 2H), 1.71 (qd, J = 11.9, 3.8 Hz, 2H).13C NMR (100 MHz, CD3OD) δ 157.63, 151.93, 148.38, 115.37, 114.61, 61.72, 49.49, 40.37, 27.84. HRMS (ESI, m / z): calculated for C12H19N3Br [M+H]+: 284.075686; found 284.07586. Example 51: Synthesis of 4-(4- 1-yl)-N-(quinoxalin-6- ylmethyl)pyridin-3-amine Prepared using general procedure 1.2 using 1-(3-bromopyridin-4-yl)-N,N- dimethylpiperidin-4-amine (28 mg, 0.1 mmol), quinoxalin-6-ylmethanamine (31 mg, 0.2 mmol), Pd2dba3 (3.6 mg, 0.004 mmol), BINAP (6.1 mg, 0.01 mmol), NaOtBu (28 mg, 0.30 mmol), and toluene (0.90 mL). The crude material was purified using RP MPLC (MeOH / 0.1% NH3 in H2O; Attorney Docket No.: 393976-00101 10-100%) then NP MPLC (0.1% NH4OH in MeOH / DCM; 0-10%) to yield 4-(4- (dimethylamino)piperidin-1-yl)-N-(quinoxalin-6-ylmethyl)pyridin-3-amine as a yellow residue (13.1 mg, 0.04 mmol, 37% yield).1H NMR (400 MHz, CD3OD) δ 8.84 (ABq, ∆^^^^= 3.4 Hz, JAB= 1.96 Hz, 2H), 8.09 (d, J = 8.6 Hz, 1H), 8.03 (d, J = 1.8 Hz, 1H), 7.91 (dd, J = 8.7, 1.9 Hz, 1H), 7.80 (d, J = 5.3 Hz, 1H), 7.67 (s, 1H), 6.99 (d, J = 5.3 Hz, 1H), 4.75 (s, 2H), 3.58 (app d, J = 12.0 Hz, 2H), 2.98 – 2.90 (m, 1H), 2.75 (td, J = 12.2, 2.2 Hz, 2H), 2.66 (s, 6H), 2.14 (app d, J = 12.3 Hz, 2H), 2.00 – 1.89 (m, 2H).13C NMR (101 MHz, CD3OD) δ 145.2, 144.8, 138.7, 131.2, 129.6, 129.0, 125.6, 113.8, 62.8, 48.8, 47.6, 47.4, 47.2, 46.9, 46.5, 39.7, 27.1. HRMS (ESI, m / z): calculated for C21H27N6 [M+H]+: 362.22, found 363.22931. Example 52: Synthesis of 4-(1H- Prepared using general procedure 2.1 using 4-chloro-3-nitropyridine (205 mg, 1.3 mmol), 1H-imidazole (176 mg, 2.6 mmol), triethylamine (0.5 mL, 3.9 mmol), and acetonitrile (1.3 mL). The crude product was purified with NP MPLC (EtOAc / Hex; 0-100%) to afford 4-(1H-imidazol- 1-yl)-3-nitropyridine as a yellow solid (180 mg, 1.0 mmol, 73% yield).1H NMR (400 MHz, CDCl3) δ 9.19 (d, J = 0.5 Hz, 1H), 8.91 (d, J = 5.3 Hz, 1H), 7.75 – 7.70 (m, 1H), 7.42 (dd, J = 5.3, 0.4 Hz, 1H), 7.26 (dd, J = 1.5, 0.8 Hz, 1H), 7.12 – 7.06 (m, 1H).13C NMR (101 MHz, CDCl3) δ 154.7, 146.9, 137.5, 136.5, 134.9, 131.6, 120.8, 119.1. HRMS (ESI, m / z): calculated for C21H27N6[M+H]+: 191.04908, found 191.05675. Example 53: Synthesis of 4-(1H- 3-amine Prepared using general procedure 2.2 using 4-(1H-imidazol-1-yl)-3-nitropyridine (245 mg, 1.3 mmol), 10 wt.% Pd / C (13.7 mg, 0.001 mmol) and MeOH (12.9 mL). The crude material was used in subsequent steps without further purification (130 mg, 0.8 mmol, 63% yield). Attorney Docket No.: 393976-00101 Example 54: Synthesis of 4-(1H- 6-ylmethyl)pyridin-3-amine Prepared using general procedure 2.3 using 4-(1H-imidazol-1-yl)-3-nitropyridine (129 mg, 0.8 mmol) and quinoxaline-6-carbaldehyde (140 mg, 0.9 mmol), EtOH (1.6 mL), and NaBH4(152 mg, 4.0 mmol, 5.0 equiv. Crude product was purified with NP MPLC (EtOAc / Hex; 0-100%) to afford 4-(1H-imidazol-1-yl)-N-(quinoxalin-6-ylmethyl)pyridin-3-amine as a white solid (81mg, 0.3 mmol, 33% yield).1H NMR (400 MHz, CD3OD) δ 8.83 (s, 2H), 8.10 – 7.99 (m, 3H), 7.92 (d, J = 5.1 Hz, 1H), 7.86 (dd, J = 8.7, 2.0 Hz, 1H), 7.50 (t, J = 1.4 Hz, 1H), 7.27 (dt, J = 1.5, 0.8 Hz, 1H), 7.22 (d, J = 5.1 Hz, 1H), 4.72 – 4.68 (m, 2H).13C NMR (101 MHz, CD3OD) δ 145.2, 144.9, 142.5, 141.9, 141.9, 139.1, 137.9, 137.3, 134.5, 130.2, 130.2, 129.5, 129.1, 129.1, 129.0, 125.7, 121.3, 121.3, 119.9, 119.9, 45.8. HRMS (ESI, m / z): calculated for C21H27N6[M+H]+: 303.12799, found 303.13562. Example 55: Synthesis of tert-Butyl (1- 4-yl)azetidin-3-yl)carbamate Prepared using general procedure 2.1 using 4-chloro-3-nitropyridine (168 mg, 1.1 mmol), tert-Butyl azetidin-3-ylcarbamate (365 mg, 2.1 mmol), and triethylamine (322 mg, 3.2 mmol), in acetonitrile (1.1 mL). The crude product was purified with NP MPLC (EtOAc / Hex; 0-100%) to afford tert-Butyl (1-(3-nitropyridin-4-yl)azetidin-3-yl)carbamate as a yellow solid (250 mg, 1.1 mmol, 80% yield).1H NMR (400 MHz, CDCl3) δ 8.87 (s, 1H), 8.26 (d, J = 6.0 Hz, 1H), 6.39 (d, J = 6.0 Hz, 1H), 5.04 (s, 1H), 4.56 (s, 1H), 4.39 (t, J = 8.8 Hz, 3H), 4.03 – 3.94 (m, 2H), 1.45 (s, 9H).13C NMR (101 MHz, CDCl3) δ 151.46, 148.04, 147.50, 109.23, 60.56, 28.28.*** HRMS (ESI, m / z): calculated for C21H27N6 [M+H]+: 295.13281, found 295.14047. Attorney Docket No.: 393976-00101 Example 56: Synthesis of tert-butyl (1- 4-yl)azetidin-3-yl)carbamate Prepared using general procedure 2.2 using tert-butyl (1-(3-nitropyridin-4-yl)azetidin-3- yl)carbamate (535.6 mg, 1.8 mmol) and 10 wt.% Pd / C (11.4 mg, 0.002 mmol) and MeOH (36.4 mL). The crude product was purified on RP MPLC (MeOH / 0.1% NH3 in H2O; 10-100%) to afford tert-butyl (1-(3-aminopyridin-4-yl)azetidin-3-yl)carbamate as a white solid (164 mg, 0.6 mmol, 34% yield).1H NMR (400 MHz, DMSO-d6) δ 7.71 (s, 1H), 7.62 (d, J = 5.2 Hz, 1H), 7.43 (d, J = 7.4 Hz, 1H), 6.25 (d, J = 5.2 Hz, 1H), 4.39 – 4.25 (m, 3H), 4.16 (t, J = 7.4 Hz, 2H), 3.56 (dd, J = 7.6, 6.2 Hz, 2H), 1.37 (s, 9H).13C NMR (101 MHz, DMSO-d6) δ 156.1144.8, 139.9, 136.8, 133.9, 108.5, 78.7, 59.5, 41.2, 28.6. HRMS (ESI, m / z): calculated for C21H27N6[M+H]+: 265.15863, found 265.16605. Example 57: Synthesis of tert- ylmethyl)amino)pyridin-4- yl)azetidin-3-yl)carbamate Prepared using general procedure 2.3 using tert-butyl (1-(3-aminopyridin-4-yl)azetidin-3- yl)carbamate (164 mg, 0.6 mmol), quinoxaline-6-carbaldehyde (108 mg, 0.7 mmol), EtOH (6.2 mL) and NaBH4(69.6 mg, 1.9 mmol). The crude product was purified with RP MPLC (MeOH / 0.1% NH3in H2O; 10-100%) to afford tert-butyl (1-(3-((quinoxalin-6- ylmethyl)amino)pyridin-4-yl)azetidin-3-yl)carbamate as a yellow solid (80 mg, 0.2 mmol, 32% yield).1H NMR (400 MHz, CD3OD) δ 8.84 (s, 1H), 8.11 – 8.03 (m, 2H), 7.90 (dd, J = 8.7, 2.0 Hz, 1H), 7.72 (d, J = 5.4 Hz, 1H), 7.51 (s, 1H), 6.50 (d, J = 5.4 Hz, 1H), 4.63 (br s, 2H), 4.52 (m, 1H), 4.40 (t, J = 7.5 Hz, 2H), 3.79 (t, J = 7.0 Hz, 2H), 1.45 (s, 9H).13C NMR (101 MHz, CD3OD) δ 168.9, 147.3, 145.1, 144.7, 142.9, 142.5, 141.9, 139.6, 134.0, 131.8, 129.9, 128.8, 125.9, 107.9, Attorney Docket No.: 393976-00101 59.6, 41.2, 27.3. HRMS (ESI, m / z): calculated for C21H27N6 [M+H]+: 407.21172, found 407.21948. Example 58: Synthesis of 4-(3- 6-ylmethyl)pyridin-3-amine Prepared using general procedure 2.4 using tert-butyl (1-(3-((quinoxalin-6- ylmethyl)amino)pyridin-4-yl)azetidin-3-yl)carbamate (79.7 mg, 0.2 mmol), TFA (0.4 mL) and DCM (2.0 mL). The crude product was purified on RP MPLC (MeOH / 0.1% NH3in H2O; 10- 100%) to afford 4-(3-aminoazetidin-1-yl)-N-(quinoxalin-6-ylmethyl)pyridin-3-amine as a yellow solid (25 mg, 0.1 mmol, 45% yield).1H NMR (400 MHz, CD3OD) δ 9.72 (q, J = 1.9 Hz, 2H), 9.66 – 9.61 (m, 3H), 9.06 (s, 1H), 8.91 (dd, J = 13.8, 7.7 Hz, 2H), 8.78 – 8.65 (m, 2H), 8.25 (d, J = 6.0 Hz, 1H), 7.82 (d, J = 6.5 Hz, 1H), 6.55 (s, 1H), 5.49 (s, 2H), 4.95 – 4.82 (m, 2H), 4.67 (s, 1H), 4.53 (tt, J = 14.9, 8.2 Hz, 2H).13C NMR (101 MHz, CD3OD) δ 164.3, 148.5, 147.1, 146.8, 143.4, 142.9, 141.9, 133.8, 133.1, 131.2, 130.6, 128.0, 118.4, 104.3, 66.3, 51.1, 46.8. HRMS (ESI, m / z): calculated for C21H27N6[M+H]+: 305.15929, found 305.15118. Example 59: Synthesis of tert-butyl (1- 4-yl)pyrrolidin-3-yl)carbamate Prepared using general procedure 1.1 using 3,4-dibromopyridine (800 mg, 3.4 mmol), DL- 3-(BOC-Amino)pyrrolidine (1.1 g, 6.1 mmol), and acetonitrile (4.2 mL). The crude material was purified using NP MPLC (EtOAc / Hex; 0-50%) to provide tert-butyl (1-(3-bromopyridin-4- yl)pyrrolidin-3-yl)carbamate as a brown residue (443 mg, 1.3 mmol, 38% yield).1H NMR (400 MHz, DMSO-d6) δ 8.28 (s, 1H), 8.06 (d, J = 5.7 Hz, 1H), 7.20 (d, J = 5.5 Hz, 1H), 6.63 (d, J = 5.8 Hz, 1H), 4.11 – 3.99 (m, 1H), 3.75 (dd, J = 10.2, 6.2 Hz, 1H), 3.66 – 3.58 (m, 1H), 3.55 – 3.47 (m, 1H), 3.42 (dd, J = 10.2, 4.7 Hz, 1H), 2.05 (m,, 1H), 1.86 (m, 1H).13C NMR (101 MHz, DMSO- Attorney Docket No.: 393976-00101 d6) δ 155.2, 152.9, 150.9, 148.0, 111.1, 104.4, 77.9, 55.7, 49.8, 48.3, 30.3, 28.2. HRMS (ESI, m / z): calculated for C14H21N3O2Br [M+H]+: 342.08118; found 342.08060. Example 60: Synthesis of 6-ylmethyl)amino)pyridin-4- yl)pyrrolidin-3-yl)carbamate Prepared using general procedure 1.2 tert-butyl (1-(3-bromopyridin-4-yl)pyrrolidin-3- yl)carbamate (200 mg, 0.6 mmol), quinoxalin-6-ylmethanamine (186 mg, 1.2 mmol), Pd2dba3(21 mg, 0.02 mmol) BINAP (29 mg, 0.05 mmol), NaOtBu (112 mg, 1.2 mmol), and toluene (5.3 mL). The crude product was purified RP MPLC (MeOH / 0.1% NH3 in H2O; 10-100%) followed by RP MPLC (MeCN / 0.1% CHCO2H in H2O; 10-100%) to yield tert-butyl (1-(3-((quinoxalin-6- ylmethyl)amino)pyridin-4-yl)pyrrolidin-3-yl)carbamate as a yellow residue (7 mg, 0.02 mmol, 3% yield).1H NMR (400 MHz, CD3OD) δ 8.86 (br s, 2H), 8.12 – 8.08 (m, 2H), 7.92 (dd, J = 8.6, 2.0 Hz, 1H), 7.79 (dd, J = 6.7, 1.0 Hz, 1H), 7.46 (s, 1H), 6.85 (d, J = 6.8 Hz, 1H), 4.61 (s, 2H), 4.29 – 4.20 (m, 1H), 4.03 (dd, J = 10.8, 6.1 Hz, 1H), 3.94 – 3.83 (m, 1H), 3.83 – 3.72 (m, 1H), 3.66 (dd, J = 10.9, 4.7 Hz, 1H), 2.32 – 2.19 (m, 1H), 2.10 – 1.98 (m, 1H).13C NMR (151 MHz, CD3OD) δ 158.0, 152.4, 146.8, 146.5, 144.0, 143.4, 142.5, 136.1, 134.0, 131.3, 130.6, 127.8, 123.2, 109.3, 80.6, 57.1, 51.5, 50.2, 40.4, 31.8, 28.7. HRMS (ESI, m / z): calculated for C23H29N6O2 [M+H]+: 421.23468; found 421.23349. Example 61: Synthesis of 4- -N-(quinoxalin-6-ylmethyl)pyridin-3- amine hydrochloride salt Prepared using general procedure 1.3 using tert-butyl (1-(3-((quinoxalin-6- ylmethyl)amino)pyridin-4-yl)pyrrolidin-3-yl)carbamate (3 mg, 0.007 mmol) in DCM (0.7 mL) and 2 M HCl in Et2O (0.07 mL, 0.1 mmol) to provide 4-(3-aminopyrrolidin-1-yl)-N-(quinoxalin- Attorney Docket No.: 393976-00101 6-ylmethyl)pyridin-3-amine hydrochloride salt as a brown residue (3 mg, 0.007 mmol, 100% yield).1H NMR (400 MHz, CD3OD) δ 8.94 (ABq, ∆υAB= 2.2 Hz, JAB= 2.0 Hz, 2H), 8.16 (d, J = 8.7 Hz, 1H), 8.02 (dd, J = 8.7, 1.9 Hz, 1H), 7.93 (dd, J = 6.7, 1.1 Hz, 1H), 7.63 (d, J = 1.0 Hz, 1H), 7.05 (d, J = 6.7 Hz, 1H), 4.70 (s, 1H), 4.20 – 4.09 (m, 3H), 3.98 – 3.92 (m, 1H), 3.80 – 3.72 (m, 1H), 2.60 – 2.49 (m, 1H), 2.34 – 2.24 (m, 1H).13C NMR (151 MHz, CD3OD) δ 152.4, 145.8, 145.6, 143.8, 142.6, 142.4, 137.0, 133.7, 132.6, 129.9, 126.7, 123.3, 111.0, 54.8, 51.4, 49.5, 30.1. HRMS (ESI, m / z): calculated for C18H21N6[M+H]+: 321.18218; found 321.18143. Purity (LC): 93% Example 62: Synthesis of tert-butyl 4- 4-yl)-1,4-diazepane-1-carboxylate Prepared using the general procedure 1.1 using 3,4-dibromopyridine (800 mg, 3.4 mmol) tert-butyl 1,4-diazepane-1-carboxylate (1.4 g, 6.8 mmol) and acetonitrile (4.2 mL). The crude material was purified using NP MPLC (EtOAc / Hex; 0-100%) to provide tert-butyl 4-(3- bromopyridin-4-yl)-1,4-diazepane-1-carboxylate as a yellow oil (650 mg, 1.8 mmol, 54% yield).1H NMR (400 MHz, DMSO-d6) mixture of rotamers: δ 8.42 (s, 1H), 8.18 (m, 1H), 7.01 (m, 1H), 3.56 – 3.49 (m, 3H), 3.48 – 3.43 and 3.43 – 3.38 (m, 4H), 1.95 – 1.86 (m, 2H), 1.37 and 1.28 (two s, rotamers, 9H).13C NMR (101 MHz, DMSO-d6) mixture of rotamers, observed resonances for minor rotamer are enclosed in parentheses: δ 155.0, (154.5), 154.4, (154.1), 153.1, (153.0), 148.6, (148.5), 114.8, (114.3), 110.4, (109.5), 78.6, (78.5), 51.8, 51.5, 46.1, (45.8), 45.3, (44.5), 28.0, (27.9), 27.5, (26.7). HRMS (ESI, m / z): calculated for C15H23N3O2Br [M+H]+: 356.09678; found 356.09641. Example 63: Synthesis of 6-ylmethyl)amino)pyridin-4-yl)-1,4- diazepane-1-carboxylate Attorney Docket No.: 393976-00101 Prepared using general procedure 1.2 using tert-butyl 4-(3-bromopyridin-4-yl)-1,4- diazepane-1-carboxylate (250 mg, 0.7 mmol), quinoxalin-6-ylmethanamine (223 mg, 1.4 mmol), Pd2dba3(13 mg, 0.01 mmol) BINAP (22 mg, 0.03 mmol), NaOtBu (135 mg, 1.4 mmol), and toluene (6.4 mL). The crude product was purified by NP MPLC (MeOH / DCM; 0-10%) followed by RP MPLC (MeOH / 0.1% NH3 in H2O; 10-100%)to yield tert-butyl 4-(3-((quinoxalin-6- ylmethyl)amino)pyridin-4-yl)-1,4-diazepane-1-carboxylate as a yellow residue (35 mg, 0.08 mmol, 11% yield).1H NMR (400 MHz, CD3OD) mixture of rotamers: δ 8.86 ( s, 2H), 8.10 (d, J = 8.7 Hz, 1H), 8.05 (br s, 1H), 7.91 (dd, J = 8.7, 1.9 Hz, 1H), 7.82 – 7.76 (m, 1H), 7.71 (d, J = 8.4 Hz, 1H), 7.03 (d, J = 5.3 Hz, 1H), 4.73 and 4.72 (two s, rotamers, 2H), 3.71 – 3.65 (m, 2H), 3.63 – 3.57 (m, 2H), 3.36 – 3.21 (m, 4H), 2.12 – 1.93 (m, 2H), 1.46 and 1.44 (two s, rotamers, 9H).13C NMR (101 MHz, CD3OD) mixture of rotamers, resonances for minor rotamer are enclosed in parentheses δ 157.7, (157.2), 149.9, (149.6), 146.6, 146.2, 144.1, 144.0, 143.3, 140.4, (140.2), 139.4, (139.3), 133.4, (133.1), 131.1, 130.4, 127.2, 116.3, (116.1), 81.2, (81.1), 54.8, (54.6), 54.4, (54.2), 48.7, (48.2), 48.0, (47.9), 47.5, (46.3), 30.0, (29.5), 28.7. HRMS (ESI, m / z): calculated for C24H31N6O2 [M+H]+: 435.25028; found 435.25004. Example 64: Synthesis of 4- 6-ylmethyl)pyridin-3-amine hydrochloride salt Prepared using general procedure 1.3 using tert-butyl 4-(3-((pyridin-3- ylmethyl)amino)pyridin-4-yl)piperazine-1-carboxylate (30 mg, 0.08 mmol) in DCM (0.8 mL) and 2 M HCl in Et2O (0.8 mL, 1.6 mmol) to yield 4-(1,4-diazepan-1-yl)-N-(quinoxalin-6- ylmethyl)pyridin-3-amine hydrochloride salt as an orange residue (15 mg, 0.07 mmol, 86% yield).1H NMR (400 MHz, CD3OD) δ 8.95 – 8.90 (m, 2H), δ 8.95 – 8.90 (m, 2H), 8.15 (d, J = 8.7 Hz, , 8.12 (d, J = 1.2 Hz, 1H), 8.02 (dd, J = 6.5, 1.2 Hz, 1H), 7.99 (dd, J = 8.8, 1.9 Hz, 1H), 7.77 (d, J = 1.1 Hz, 1H), 7.43 (d, J = 6.5 Hz, 1H), 4.77 (s, 2H), 4.01 – 3.93 (m, 2H), 3.79 – 3.67 (m, 2H), 3.61 – 3.55 (m, 2H), 3.52 – 3.46 (m, 2H), 2.42 – 2.26 (m, 2H).13C NMR (101 MHz, CD3OD) δ 155.4, 146.6, 146.4, 143.6, 143.3, 142.4, 140.6, 133.1, 131.4, 130.6, 127.4, 123.5, 52.8, 49.3, Attorney Docket No.: 393976-00101 48.2, 46.8, 46.6, 26.4. Peak at 49.3 ppm identified via HSQC. HRMS (ESI, m / z): calculated for C19H23N6 [M+H]+: 335.19788; found 335.19753.Purity (LC): 98% Example 65: Synthesis of tert- 4-yl)amino)azetidine-1-carboxylate Prepared according to general procedure 2.1 using 4-chloro-3-nitropyridine (338 mg, 2.1 mmol), tert-butyl 3-aminoazetidine-1-carboxylate (734 mg, 4.3 mmol), and triethylamine (642 mg, 6.4 mmol), and acetonitrile (2.1 mL). The crude product was purified on NP MPLC (EtOAc / Hex; 0-100%) to afford tert-butyl 3-((3-nitropyridin-4-yl)amino)azetidine-1-carboxylate as a yellow solid (314 mg, 2.1 mmol, 50% yield).1H NMR (401 MHz, CDCl3) δ 9.25 (s, 1H), 8.35 (dd, J = 6.1, 0.7 Hz, 1H), 6.43 (d, J = 6.0 Hz, 1H), 4.38 (m, 3H), 3.91 (m, 2H), 1.64 (br s, 1H), 1.45 (s, 9H).13C NMR (101 MHz, CDCl3) δ 155.8, 149.1, 147.2, 130.3, 107.6, 80.4, 56.2, 42.1, 28.3. HRMS (ESI, m / z): calculated for C19H23N6 [M+H]+: 295.13281; found 295.14047. Example 66: Synthesis of tert-butyl 4-yl)amino)azetidine-1-carboxylate Prepared according to general procedure 2.1 using 4-chloro-3-nitropyridine (338 mg, 2.1 mmol), tert-Butyl 3-aminoazetidine-1-carboxylate (734 mg, 4.3 mmol), and triethylamine (642 mg, 6.4 mmol), and acetonitrile (2.1 mL). The crude product was purified on NP MPLC (EtOAc / Hex; 0-100%) to afford tert-butyl 3-((3-nitropyridin-4-yl)amino)azetidine-1-carboxylate as a yellow solid (314.1 mg, 2.1 mmol, 50% yield).1H NMR (401 MHz, MeCN-d3) δ 7.82 (s, 1H), 7.77 (dd, J = 0.66, 5.30 Hz, 1H), 6.26 (d, J = 5.28 Hz, 1H), 4.75 (br s, 1H), 4.27 (m, 3H), 3.76 (m, 2H), 3.69 (br s, 2H), 1.45 (s, 9H).13C NMR (101 MHz, MeCN-d3) δ 141.7, 141.1, 136.4, 130.8, 105.1, 78.9, 48.9, 42.4, 27.5. HRMS (ESI, m / z): calculated for C19H23N6 [M+H]+: 265.15863; found 265.16653 Attorney Docket No.: 393976-00101 Example 67: Synthesis 6-ylmethyl)amino)pyridin-4- yl)amino)azetidine-1-carboxylate Prepared according to general procedure 2.3 using tert-butyl 3-((3-aminopyridin-4- yl)amino)azetidine-1-carboxylate (163 mg, 0.6 mmol), quinoxaline-6-carbaldehyde (107 mg, 0.7 mmol), NaBH4 (70 mg, 1.8 mmol) and EtOH (6.2 mL). The crude product was purified with RP MPLC (MeOH / 0.1% NH3in H2O; 10-100%) to afford tert-butyl 3-((3-((quinoxalin-6- ylmethyl)amino)pyridin-4-yl)amino)azetidine-1-carboxylate as a yellow solid (40 mg, 0.1 mmol, 16% yield).1H NMR (400 MHz, CD3OD) δ 8.83 (s, 2H), 8.14 – 8.04 (m, 2H), 7.90 (dd, J = 8.7, 2.0 Hz, 1H), 7.67 (d, J = 5.5 Hz, 1H), 7.50 (s, 1H), 6.35 (d, J = 5.6 Hz, 1H), 4.67 (s, 2H), 4.35 (d, J = 4.4 Hz, 3H), 3.85 (d, J = 4.7 Hz, 2H), 1.43 (s, 9H).13C NMR (101 MHz, CD3OD) δ 156.7, 145.2, 144.8, 142.5, 142.4, 142.3, 141.9, 139.0, 131.7, 130.0, 129.0, 128.9, 126.1, 104.2, 79.8, 46.8, 42.3, 27.2. HRMS (ESI, m / z): calculated for C19H23N6[M+H]+: 407.21172; found 407.21948. Example 68: Synthesis of 6-ylmethyl)pyridine-3,4-diamine hydrochloride salt Prepared according to general procedure 2.4 using tert-butyl 3-((3-((quinoxalin-6- ylmethyl)amino)pyridin-4-yl)amino)azetidine-1-carboxylate (40 mg, 0.1 mmol), DCM (1.0 mL), and 2 M HCl in ether (1.2 mL) to yield N4-(azetidin-3-yl)-N3-(quinoxalin-6-ylmethyl)pyridine- 3,4-diamine hydrochloride salt (30.4 mg, quant.).1H NMR (400 MHz, DMSO-d6) δ 13.71 (s, 1H), 9.49 (s, 1H), 9.30 (s, 1H), 9.07 (d, J = 5.5 Hz, 1H), 8.92 (t, J = 1.4 Hz, 2H), 8.14 – 8.07 (m, 2H), 7.94 (dd, J = 8.7, 1.9 Hz, 1H), 7.83 (t, J = 5.8 Hz, 1H), 7.64 (s, 1H), 7.47 (d, J = 4.5 Hz, 1H), 6.67 (d, J = 6.6 Hz, 1H), 4.72 (s, 2H), 4.43 – 4.24 (m, 4H).13C NMR (101 MHz, DMSO-d6) δ 146.3, Attorney Docket No.: 393976-00101 145.9, 145.9, 142.6, 142.1, 141.1, 132.9, 131.89, 130.4, 129.8, 127.2, 117.5, 103.8, 51.6, 45.7, 44.8, 34.6. HRMS (ESI, m / z): calculated for C19H23N6 [M+H]+: 307.15929; found 307.16669. Example 69: Synthesis of tert-butyl 4-yl)oxy)azetidine-1-carboxylate a Prepared using general procedure 2.1 using 4-chloro-3-nitropyridine (340 mg, 2.1 mmol), tert-butyl 3-hydroxyazetidine-1-carboxylate (743 mg, 4.3 mmol), and triethylamine (651 mg, 6.4 mmol), and acetonitrile (2.1 mL). The crude product was purified using NP MPLC (EtOAc / Hex; 0-100%) to afford tert-butyl 3-((3-nitropyridin-4-yl)oxy)azetidine-1-carboxylate as a yellow solid (500 mg, 1.7 mmol, 79% yield).1H NMR (400 MHz, CDCl3) δ 9.02 (s, 1H), 8.60 (d, J = 5.8 Hz, 1H), 6.64 (d, J = 5.8 Hz, 1H), 5.04 (tt, J = 6.4, 4.0 Hz, 1H), 4.35 (ddd, J = 10.0, 6.4, 1.2 Hz, 2H), 4.15 – 4.03 (m, 2H), 1.42 (s, 9H).13C NMR (101 MHz, CDCl3) δ 156.1, 155.7, 154.8, 147.5, 136.7, 109.0, 80.4, 67.8, 30.9, 28.3. HRMS (ESI, m / z): calculated for C19H23N6 [M+H]+: 295.11682 Example 70: Synthesis of tert- 4-yl)oxy)azetidine-1-carboxylate Prepared according to general procedure 2.2 using tert-butyl 3-((3-nitropyridin-4- yl)oxy)azetidine-1-carboxylate (500 mg, 1.7 mmol) and 10 wt.% Pd / C (18 mg, 0.02 mmol) and MeOH (117 mL) to afford tert-butyl 3-((3-aminopyridin-4-yl)oxy)azetidine-1-carboxylate a red oil (194 mg, 0.7 mmol, 43% yield). This material was used in subsequent steps without further purification. Attorney Docket No.: 393976-00101 Example 71: Synthesis of tert-butyl 3-((3-((quinoxalin-6-ylmethyl)amino)pyridin-4- yl)oxy)azetidine-1-carboxylate Prepared according to general procedure 2.3 using tert-butyl 3-((3-aminopyridin-4- yl)oxy)azetidine-1-carboxylate (185 mg, 0.7 mmol), quinoxaline-6-carbaldehyde (121 mg, 0.8 mmol), NaBH4 (79 mg, 2.1 mmol), and EtOH (7.0 mL). The crude product was purified using RP MPLC (MeOH / 0.1% NH3in H2O; 10-100%) to afford tert-butyl 3-((3-((quinoxalin-6- ylmethyl)amino)pyridin-4-yl)oxy)azetidine-1-carboxylate as a yellow solid (34.0 mg, 0.1 mmol, 12% yield).1H NMR (400 MHz, CD3OD) δ 8.79 (s, 2H), 8.06 – 7.97 (m, 2H), 7.85 (dd, J = 8.7, 2.0 Hz, 1H), 7.70 (d, J = 5.4 Hz, 1H), 7.62 (s, 1H), 6.59 (d, J = 5.4 Hz, 1H), 5.11 (tt, J = 6.3, 3.8 Hz, 1H), 4.69 (d, J = 1.2 Hz, 2H), 4.43 – 4.35 (m, 2H), 4.08 – 4.00 (m, 2H), 1.43 (s, 9H).13C NMR (101 MHz, CD3OD) δ 156.6, 150.3, 145.1, 144.7, 142.6, 142.5, 141.8, 138.4, 134.7, 130.6, 129.6, 128.9, 125.7, 106.0, 80.0, 66.4, 56.1, 46.0, 27.2. Example 72: Synthesis 6-ylmethyl)pyridin-3-amine hydrochloride salt Prepared according to general procedure 2.4 using tert-butyl 3-((3-((quinoxalin-6- ylmethyl)amino)pyridin-4-yl)oxy)azetidine-1-carboxylate (34.0 mg, 0.08 mmol), DCM (0.9 mL) and 2 M HCl in ether (1.1 mL). The crude material was purified with RP MPLC (MeOH / 0.1% NH3in H2O; 10-100%)) to afford 4-(azetidin-3-yloxy)-N-(quinoxalin-6-ylmethyl)pyridin-3-amine as a yellow solid (26 mg, 0.09 mmol, 98% yield).1H NMR (400 MHz, DMSO-d6) δ 15.28 (s, 1H), 9.94 (s, 1H), 9.78 (s, 1H), 8.92 (s, 2H), 8.14 – 8.05 (m, 3H), 7.97 – 7.87 (m, 2H), 7.58 (s, 1H), 7.29 (d, J = 6.4 Hz, 1H), 5.48 (qd, J = 6.5, 4.6 Hz, 1H), 4.79 (d, J = 4.6 Hz, 2H), 4.52 (p, J = 5.9 Hz, 2H), 4.27 (dd, J = 11.0, 6.1 Hz, 2H).13C NMR (101 MHz, DMSO-d6) δ 154.7, 146.2, 145.9, 142.5, 142.0, 141.0, 137.4, 131.6, 130.3, 129.8, 126.9, 120.1, 108.5, 69.8, 51.6, 45.3. HRMS (ESI, m / z): calculated for C19H23N6[M+H]+: 308.15929; found 308.15097. Attorney Docket No.: 393976-00101 Example 73: Synthesis of tert-butyl 4-yl)amino)pyrrolidine-1-carboxylate Prepared using general 3-nitropyridine (700 mg, 4.4 mmol), tert-butyl 3-aminopyrrolidine-1-carboxylate (1.6 g, 8.8 mmol), triethylamine (2 mL, 13.2 mmol), and acetonitrile (5.5 mL). The crude material was purified using NP MPLC (EtOAc / Hex; 0-100%) to yield tert-butyl 3-((3-nitropyridin-4-yl)amino)pyrrolidine-1-carboxylate as a yellow amorphous solid (1.1 g, 3.5 mmol, 79% yield).1H NMR (400 MHz, CDCl3) δ 9.20 (d, J = 2.9 Hz, 1H), 8.40 – 8.26 (m, 1H), 8.24 – 8.14 (m, 1H), 6.70 (d, J = 6.2 Hz, 1H), 4.25 – 4.13 (m, 1H), 3.81 – 3.72 (m, 1H), 3.62 – 3.44 (m, 2H), 3.42 – 3.27 (m, 1H), 2.31 (dtd, J = 13.6, 7.9, 5.9 Hz, 1H), 2.06 – 1.95 (m, 1H), 1.44 (s, 9H).13C NMR (101 MHz, CD3OD) δ 154.9, 152.0, 148.2, 147.8, 130.1, 108.8, 79.9, 52.0, 51.3, 50.9, 50.5, 43.9, 43.5, 30.9, 30.1, 27.3. (Rotamers) HRMS (ESI, m / z): calculated for C14H21N4O4 [M+H]+: 309.155736; found 309.15568. Example 74: Synthesis of tert-butyl 4-yl)amino)pyrrolidine-1-carboxylate Prepared using general procedure 2.2 using tert-butyl 3-((3-nitropyridin-4- yl)amino)pyrrolidine-1-carboxylate (515 mg, 1.7 mmol), Pd / C (17.8 mg, 0.2 mmol), and methanol (16.7 mL). The crude material was purified using RP MPLC (MeOH / 0.1% NH3in H2O; 10-100%) to yield tert-butyl 3-((3-aminopyridin-4-yl)amino)pyrrolidine-1-carboxylate as a fluffy white solid (300 mg, 1.1 mmol, 65% yield).1H NMR (400 MHz, DMSO-d6) δ 7.61 (s, 1H), 7.55 (d, J = 5.3 Hz, 1H), 6.35 (d, J = 5.3 Hz, 1H), 5.27 (d, J = 6.2 Hz, 1H), 4.60 (s, 2H), 4.03 – 3.98 (m, 1H), 3.57 – 3.50 (m, 1H), 3.42 – 3.31 (m, 1H), 3.16 – 3.05 (m, 2H), 2.16 – 2.06 (m, 1H), 1.81 – 1.77 (m, 1H), 1.36 (s, 9H).13C NMR (101 MHz, DMSO-d6) δ 154.0, 140.4, 134.0, 134.9, 131.5, 105.1, 78.8, 31.7, 29.5, 29.4, 28.6, 14.4. HRMS (ESI, m / z): calculated for C14H23N4O2 [M+H]+: 279.18156; found 279.18240. Attorney Docket No.: 393976-00101 Example 75: Synthesis 6-ylmethyl)amino)pyridin-4- yl)amino)pyrrolidine-1- To round bottom flask containing tert-butyl 3-((3-aminopyridin-4-yl)amino)pyrrolidine-1- carboxylate (200 mg, 0.7 mmol), quinoxaline-6-carbaldehyde (125 mg, 0.9 mmol) was added followed by ethanol (3.35 mL). The reaction was refluxed for 16 h. The crude material was purified using RP MPLC (MeOH / 0.1% NH3in H2O; 10-100%) to yield tert-butyl 3-((3-((quinoxalin-6- ylmethyl)amino)pyridin-4-yl)amino)pyrrolidine-1-carboxylate as a yellow amorphous solid (51 mg, 0.3 mmol, 36% yield).1H NMR (400 MHz, CD3OD) δ 8.91 – 8.83 (m, 3H), 8.53 – 8.42 (m, 2H), 8.12 – 8.01 (m, 3H), 6.74 (d, J = 5.8 Hz, 1H), 4.27 – 4.22 (m, 1H), 3.78 – 3.69 (m, 1H), 3.57 – 3.49 (m, 1H), 3.46 – 3.41 (m, 1H), 3.36 – 3.30 (overlapping with methanol) (m, 2H), 2.29 (dq, J = 13.4, 6.7 Hz, 1H), 2.09 – 1.97 (m, 1H), 1.42 (s, 9H).13C NMR (101 MHz, CD3OD) δ 158.2, 147.7, 146.1, 146.0, 144.3, 142.7, 138.0, 135.8, 131.4, 129.3, 128.3, 105.2, 48.1, 41.4, 31.6, 29.3, 29.0, 27.3, 22.3. HRMS (ESI, m / z): calculated for C23H27N6O2[M+H]+: 419.21900; found 419.21907. Example 76: Synthesis 6-ylmethyl)amino)pyridin-4- yl)amino)pyrrolidine-1-carboxylate A round bottom flask containing tert-butyl (E)-3-((3-((quinoxalin-6- ylmethylene)amino)pyridin-4-yl)amino)pyrrolidine-1-carboxylate (140 mg, 0.3 mmol) and EtOH (3.4 mL) was cooled to 0 °C and then NaBH4(64 mg, 1.7 mmol) was added portion-wise while stirring over 4 hours. Upon completion, the reaction was diluted with sat. NaHCO3 solution and extracted three times with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated. The crude material was purified using RP MPLC (MeOH / 0.1% NH3 in H2O; 10-100%) to yield tert-butyl 3-((3-((quinoxalin-6- Attorney Docket No.: 393976-00101 ylmethyl)amino)pyridin-4-yl)amino)pyrrolidine-1-carboxylate as a yellow residue (51 mg, 0.1 mmol, 36% yield).1H NMR (400 MHz, CD3OD) δ 8.85 (s, 2H), 8.13 – 8.04 (m, 2H), 7.89 (dd, J = 8.7, 2.0 Hz, 1H), 7.81 (dd, J = 6.7, 1.1 Hz, 1H), 7.44 (d, J = 1.1 Hz, 1H), 6.93 (d, J = 6.7 Hz, 1H), 4.70 (s, 2H), 4.43 – 4.38 (m, 1H), 3.83 – 3.74 (m, 1H), 3.55 – 3.49 (m, 2H), 3.41 (dd, J = 11.3, 4.0 Hz, 1H), 2.39 – 2.31 (m, 1H), 2.13 – 2.06 (m, 1H), 1.45 (s, 9H).13C NMR (101 MHz, CD3OD) δ 154.8, 147.1, 145.4, 145.1, 142.5, 142.1, 140.5, 132.5, 132.0, 129.9, 129.2, 126.5, 117.7, 103.2, 79.9, 52.1, 50.6, 50.2, 46.5, 43.5, 30.4, 29.7, 27.3. HRMS (ESI, m / z): calculated for C23H29N6O2 [M+H]+: 421.234646; found 421.23469. Example 77: Synthesis 6-ylmethyl)pyridine-3,4- diamine hydrochloride salt Prepared using general procedure 2.4 using tert-butyl 3-((3-((quinoxalin-6- ylmethyl)amino)pyridin-4-yl)amino)pyrrolidine-1-carboxylate (25 mg, 0.06 mmol), 2 M HCl in Et2O (0.30 mL, 0.6 mmol), and DCM (0.004 mL) to provide N4-(pyrrolidin-3-yl)-N3-(quinoxalin- 6-ylmethyl)pyridine-3,4-diamine hydrochloride salt as a black solid (20 mg, 0.05 mmol, 86% yield).1H NMR (400 MHz, CD3OD) δ 9.17 (ABq, ∆^^^^= 6.96 Hz, JAB= 2.32 Hz, 2H), 8.30 – 8.25 (m, 2H), 8.18 (dd, J = 8.8, 1.9 Hz, 1H), 7.86 (dd, J = 6.7, 1.1 Hz, 1H), 7.48 (s, 1H), 6.99 (d, J = 6.7 Hz, 1H), 4.82 (s, 2H), 4.70 – 4.64 (m, 1H), 3.75 – 3.64 (m, 2H), 3.59 (dd, J = 12.4, 3.4 Hz, 1H), 3.54 – 3.50 (m, 1H), 2.59 – 2.45 (m, 1H), 2.40 – 2.31 (m, 1H).13C NMR (101 MHz, CD3OD) δ 147.0, 144.2, 144.1, 142.3, 140.9, 140.8, 132.9, 132.0, 131.3, 128.2, 125.3, 117.8, 103.5, 49.5, 44.2, 33.3, 29.9. HRMS (ESI, m / z): 320.17. Purity (LC): 97% Example 78: Synthesis of tert-butyl yl)amino)piperidine-1-carboxylate Prepared according to general procedure 2.1 using 4-chloro-3-nitropyridine (539 mg, 3.4 mmol), tert-butyl 4-aminopiperidine-1-carboxylate (1.0 g, 5.1 mmol), triethylamine (1.0 g, 10.2 Attorney Docket No.: 393976-00101 mmol), and acetonitrile (3.4 mL). The crude product was purified on NP MPLC (EtOAc / Hex; 0- 100%) to afford tert-butyl 4-((3-nitropyridin-4-yl)amino)piperidine-1-carboxylate as a yellow solid (978 mg, 3.0 mmol, 89% yield).1H NMR (400 MHz, CDCl3) δ 9.21 (s, 1H), 8.28 (dd, J = 6.2, 0.8 Hz, 1H), 8.16 (d, J = 7.5 Hz, 1H), 6.71 (d, J = 6.2 Hz, 1H), 4.04 (d, J = 13.7 Hz, 2H), 3.68 (ddt, J = 13.9, 10.3, 5.4 Hz, 1H), 3.02 (t, J = 12.3 Hz, 2H), 2.04 (d, J = 13.0 Hz, 2H), 1.63 – 1.49 (m, 4H), 1.46 (s, 9H).13C NMR (101 MHz, CDCl3) δ 154.5, 153.2, 149.4, 147.5, 129.8, 107.7, 80.1, 49.5, 42.6, 31.4, 28.4. HRMS (ESI, m / z): calculated for C19H23N6[M+H]+: 323.16411; found 323.17163. Example 79: Synthesis of tert-butyl 4-yl)amino)piperidine-1-carboxylate Prepared according to general procedure 2.2 using tert-butyl 4-((3-nitropyridin-4- yl)amino)piperidine-1-carboxylate (317 mg, 1.0 mmol), 10 wt.% Pd / C (11 mg, 0.01 mmol) and MeOH (9.8 mL) to afford tert-butyl 4-((3-aminopyridin-4-yl)amino)piperidine-1-carboxylate as a red oil (260 mg, 0.9 mmol, 90% yield) that was used in subsequent steps without further purification. Example 80: Synthesis 6-ylmethyl)amino)pyridin-4- yl)amino)piperidine-1-carboxylate Prepared according to general procedure 2.3 using tert-butyl 4-((3-aminopyridin-4- yl)amino)piperidine-1-carboxylate (260 mg, 0.9 mmol) and quinoxaline-6-carbaldehyde (157 mg, 1.0 mmol), EtOH (8.9 mL), and NaBH4 (100 mg, 2.7 mmol). The crude product was purified on RP MPLC (MeOH / 0.1% NH3 in H2O; 10-100%) to afford tert-butyl 4-((3-((quinoxalin-6- ylmethyl)amino)pyridin-4-yl)amino)piperidine-1-carboxylate as a yellow solid (48 mg, 0.1 mmol, 12% yield).1H NMR (400 MHz, CD3OD) δ 8.82 (s, 2H), 8.09 – 8.00 (m, 2H), 7.88 (dd, J = 8.7, Attorney Docket No.: 393976-00101 2.0 Hz, 1H), 7.65 (d, J = 5.6 Hz, 1H), 7.46 (s, 1H), 6.59 (d, J = 5.6 Hz, 1H), 4.62 (s, 2H), 4.06 (d, J = 13.9 Hz, 2H), 3.63 (tq, J = 7.8, 3.9 Hz, 1H), 2.98 (s, 2H), 2.05 (dd, J = 13.1, 3.3 Hz, 2H), 1.44 (m, 12H).13C NMR (101 MHz, CD3OD) δ 155.1, 145.1, 144.7, 142.7, 142.6, 142.5, 141.9, 130.8, 130.6, 130.0, 128.8, 126.1, 104.0, 79.7, 49.0, 44.7, 31.4, 27.2. HRMS (ESI, m / z): calculated for C19H23N6 [M+H]+: 435.24302; found 435.25079. Example 81: Synthesis of ylmethyl)pyridine-3,4-diamine hydrochloride salt Prepared according to general procedure 2.4 using tert-butyl 4-((3-((quinoxalin-6- ylmethyl)amino)pyridin-4-yl)amino)piperidine-1-carboxylate (48 mg, 0.1 mmol), DCM (1.1 mL), and 2 M HCl in ether (1.4 mL). Upon reaction completion, the reaction mixture was concentrated under a stream of nitrogen gas to afford N4-(piperidin-4-yl)-N3-(quinoxalin-6-ylmethyl)pyridine- 3,4-diamine hydrochloride salt as a yellow solid (36 mg, 0.1 mmol, quant.).1H NMR (400 MHz, DMSO-d6) δ 13.74 (s, 1H), 9.48 (d, J = 10.3 Hz, 1H), 9.11 (d, J = 10.3 Hz, 1H), 8.88 (t, J = 1.7 Hz, 2H), 8.11 (s, 1H), 8.08 – 8.01 (m, 4H), 7.89 (dd, J = 8.6, 1.9 Hz, 2H), 7.76 (t, J = 6.4 Hz, 1H), 7.31 (d, J = 6.0 Hz, 1H), 6.90 (d, J = 6.6 Hz, 1H), 4.63 (s, 2H), 3.96 (s, 1H), 3.31 (s, 2H), 2.99 (q, J = 11.4 Hz, 2H), 2.11 – 2.02 (m, 2H), 2.01 – 1.85 (m, 2H).13C NMR (101 MHz, DMSO-d6) δ 146.0, 145.9, 145.5, 145.5, 142.1, 141.6, 140.9, 132.1, 130.0, 129.4, 126.7, 116.7, 102.7, 47.4, 45.4, 41.9, 27.6. HRMS (ESI, m / z): calculated for C19H23N6 [M+H]+: 335.19059; found 335.19800. Example 82: Synthesis of tert- bromopyridin-4-yl)-2-methylpiperazine-1- carboxylate Attorney Docket No.: 393976-00101 Prepared using general procedure 1.1 using 3,4-dibromopyridine (193 mg, 0.8 mol), tert- butyl (S)-2-methylpiperazine-1-carboxylate (326 mg, 1.6 mmol), and acetonitrile (1.0 mL). The crude material was purified using NP MPLC (EtOAc / Hex; 0-100%) to yield tert-butyl (S)-4-(3- bromopyridin-4-yl)-2-methylpiperazine-1-carboxylate as a yellow residue (159 mg, 0.4 mmol, 55% yield).1H NMR (400 MHz, CD3OD) δ 8.49 (s, 1H), 8.30 (d, J = 5.5 Hz, 1H), 7.05 (d, J = 5.6 Hz, 1H), 4.35 (dtt, J = 10.3, 6.5, 2.2 Hz, 1H), 3.95 (dddd, J = 13.4, 3.2, 2.1, 0.9 Hz, 1H), 3.58 – 3.52 (m, 1H), 3.50 (dt, J = 11.9, 2.1 Hz, 1H), 3.36 – 3.28 (m, 2H), 2.93 (dd, J = 11.9, 3.7 Hz, 1H), 2.76 (td, J = 12.0, 3.3 Hz, 1H), 1.48 (s, 9H), 1.36 (d, J = 6.7 Hz, 3H).13C NMR (101 MHz, CD3OD) δ 157.7, 154.9, 152.1, 148.7, 115.7, 114.9, 80.0, 53.9, 50.1, 38.5, 27.3, 14.5. HRMS (ESI, m / z): 356.096816. Example 83: Synthesis of tert- 6-ylmethyl)amino)pyridin- 4-yl)piperazine-1-carboxylate Prepared using general procedure 1.2 using tert-butyl (S)-4-(3-bromopyridin-4-yl)-2- methylpiperazine-1-carboxylate (159 mg, 0.4 mmol), quinoxalin-6-ylmethanamine (120 mg, 0.8 mmol), Pd2dba3 (16.3 mg, 0.02 mmol), BINAP (28 mg, 0.4 mmol), NaOtBu (129 mg, 1.3 mmol), and toluene (4.1 mL). The crude material was purified using RP MPLC (MeOH / 0.1% NH3in H2O; 10-100%) to yield tert-butyl (S)-2-methyl-4-(3-((quinoxalin-6-ylmethyl)amino)pyridin-4- yl)piperazine-1-carboxylate as a yellow residue (96 mg, 0.2 mmol, 50% yield).1H NMR (400 MHz, CD3OD) δ 8.82 (s, 2H), 8.11 – 8.01 (m, 2H), 7.89 (dd, J = 8.6, 2.0 Hz, 1H), 7.82 (d, J = 5.3 Hz, 1H), 7.74 (s, 1H), 6.95 (d, J = 5.3 Hz, 1H), 4.76 (dd, J = 16.2, 1.1 Hz, 1H), 4.66 (dd, J = 16.1, 1.1 Hz, 1H), 4.42 – 4.34 (m, 1H), 3.96 (dt, J = 11.4, 2.2 Hz, 1H), 3.46 – 3.35 (m, 2H), 3.20 (dt, J = 11.7, 1.9 Hz, 1H), 2.88 (dd, J = 11.7, 3.8 Hz, 1H), 2.67 – 2.55 (m, 1H), 1.47 (s, 9H), 1.35 (d, J = 6.8 Hz, 3H).13C NMR (101 MHz, CD3OD) δ 154.9, 146.7, 145.2, 144.9, 142.6, 142.5, 139.1, 138.3, 131.6, 129.7, 129.0, 125.9, 113.8, 79.9, 54.1, 49.9, 46.7, 38.9, 29.6, 27.3, 14.4. HRMS (ESI, m / z): calculated for C24H31N6O2[M+H]+: 435.250296; found 435.25053. Attorney Docket No.: 393976-00101 Example 84: Synthesis of (S)-4- -N-(quinoxalin-6-ylmethyl)pyridin-3- amine Prepared using general procedure 1.3 using tert-butyl (S)-2-methyl-4-(3-((quinoxalin-6- ylmethyl)amino)pyridin-4-yl)piperazine-1-carboxylate (30 mg, 0.07 mmol) and 2 M HCl in Et2O (0.35 mL, 0.7 mmol). The crude material was purified using RP MPLC (MeOH / 0.1% NH3 in H2O; 10-100%) to provide (S)-4-(3-methylpiperazin-1-yl)-N-(quinoxalin-6-ylmethyl)pyridin-3-amine(19 mg, 0.06 mmol, 82% yield) as a yellow residue. 1H NMR (400 MHz, CD3OD) δ 8.83 (ABq,∆^^^^ = 2.4 Hz, JAB = 1.96 Hz, 2H), 8.05 – 7.99 (m, 1H), 7.89 (dd, J = 8.7, 1.9 Hz, 1H), 7.80 (d, J= 5.3 Hz, 1H), 7.67 (s, 1H), 6.96 (d, J = 5.3 Hz, 1H), 4.73 (s, 2H), 3.38 – 3.32 (m, 2H), 3.18 – 3.08 (m, 3H), 2.72 (ddd, J = 11.8, 10.0, 4.5 Hz, 1H), 2.46 – 2.36 (m, 1H), 1.16 (d, J = 6.5 Hz, 3H).13C NMR (101 MHz, CD3OD) δ 146.7, 145.2, 144.8, 142.9, 142.6, 141.9, 138.9, 138.1, 131.6, 129.6, 128.9, 125.6, 113.6, 56.5, 50.3, 49.3, 46.5, 45.0, 17.7. HRMS (ESI, m / z): calculated for C19H23N6 [M+H]+: 335.197866; found 335.19802. Purity (LC): >99% Example 85: Synthesis of tert- bromopyridin-4-yl)-2-methylpiperazine-1- carboxylate Prepared using general procedure 1.1 using 3,4-dibromopyridine (253 mg, 1.1 mmol), tert- butyl (R)-2-methylpiperazine-1-carboxylate (427 mg, 2.1 mmol), and acetonitrile (1.1 mL). The crude material was purified using NP MPLC (EtOAc / Hex; 0-100%) to provide tert-butyl (R)-4- (3-bromopyridin-4-yl)-2-methylpiperazine-1-carboxylate as a white solid (150 mg, 0.4 mmol, 40% yield).1H NMR (400 MHz, CD3OD) δ 8.48 (s, 1H), 8.29 (d, J = 5.5 Hz, 1H), 7.04 (d, J = 5.6 Hz, 1H), 4.35 (s, 1H), 3.94 (d, J = 13.3 Hz, 1H), 3.59 – 3.42 (m, 2H), 3.30 (td, J = 13.2, 2.8 Hz, Attorney Docket No.: 393976-00101 1H), 2.92 (dd, J = 11.8, 3.6 Hz, 1H), 2.75 (td, J = 11.9, 3.3 Hz, 1H), 1.47 (s, 9H), 1.35 (d, J = 6.8 Hz, 3H).13C NMR (101 MHz, CD3OD) δ 157.7, 154.9, 152.1, 148.6, 115.7, 114.9, 80.0, 53.8, 50.1, 38.5, 27.2, 14.5. HRMS (ESI, m / z): calculated for C15H23N3O2Br [M+H]+: 356.096816; found 356.09700. Example 86: Synthesis of tert- 6-ylmethyl)amino)pyridin- 4-yl)piperazine-1-carboxylate Prepared using general procedure 1.2 using tert-butyl (R)-4-(3-bromopyridin-4-yl)-2- methylpiperazine-1-carboxylate (150 mg, 0.4 mmol), quinoxalin-6-ylmethanamine (101 mg, 0.6 mmol), Pd2dba3(15.4 mg, 0.02 mmol), BINAP (26.2 mg, 0.04 mmol), NaOtBu (121 mg, 1.3 mmol), and toluene (3.8 mL). The crude material was purified using RP MPLC (MeOH / 0.1% NH3in H2O; 10-100%) then NP MPLC (MeOH / DCM; 0-10%) to provide tert-butyl (R)-2-methyl-4- (3-((quinoxalin-6-ylmethyl)amino)pyridin-4-yl)piperazine-1-carboxylate as a yellow residue (103 mg, 0.2 mmol, 56% yield).1H NMR (400 MHz, CD3OD) δ 8.84 (q, 2H), 8.09 (d, J = 8.7 Hz, 1H), 8.05 (s, 1H), 7.90 (dd, J = 8.7, 1.9 Hz, 1H), 7.82 (d, J = 5.2 Hz, 1H), 7.73 (s, 1H), 6.98 (d, J = 5.3 Hz, 1H), 4.85 (s, 3H), 4.42 – 4.35 (m, 1H), 4.02 – 3.93 (m, 1H), 3.48 – 3.36 (m, 2H), 3.23 (d, J = 11.7 Hz, 1H), 2.94 – 2.86 (m, 1H), 2.64 (dd, J = 12.5, 3.8 Hz, 1H), 1.48 (s, 9H), 1.36 (d, J = 6.8 Hz, 3H).13C NMR (101 MHz, CD3OD) δ 154.9, 147.0, 145.2, 144.9, 142.6, 142.5, 141.9, 138.9, 131.2, 129.7, 129.0, 125.9, 113.8, 80.0, 49.8, 46.7, 38.8, 29.4, 27.3, 14.4. HRMS (ESI, m / z): calculated for C24H31N6O2[M+H]+: 435.250296; found 435.35042. Example 87: Synthesis of (R)-4- -N-(quinoxalin-6-ylmethyl)pyridin-3- amine Attorney Docket No.: 393976-00101 Prepared using general procedure 1.3 using tert-butyl (R)-2-methyl-4-(3-((quinoxalin-6- ylmethyl)amino)pyridin-4-yl)piperazine-1-carboxylate (50 mg, 0.1 mmol), 2 M HCl in Et2O (0.6 mL, 1.2 mmol), and dichloromethane (0.007 mL). The crude material was purified using RP MPLC (MeOH / 0.1% NH3 in H2O; 10-100%) to provide (R)-4-(3-methylpiperazin-1-yl)-N- (quinoxalin-6-ylmethyl)pyridin-3-amine as a yellow residue (21 mg, 0.05 mmol, 51% yield).1H NMR (400 MHz, DMSO-d6) δ 8.88 (q, J = 1.9 Hz, 2H), 8.06 (d, J = 8.6 Hz, 1H), 7.98 (d, J = 1.8 Hz, 1H), 7.86 (dd, J = 8.6, 1.9 Hz, 1H), 7.76 (d, J = 5.1 Hz, 1H), 7.69 (s, 1H), 6.81 (d, J = 5.1 Hz, 1H), 5.62 (t, J = 6.2 Hz, 1H), 4.66 (d, J = 6.1 Hz, 2H), 3.20 – 3.10 (m, 2H), 3.02 – 2.89 (m, 3H), 2.57 – 2.50 (m, 1H), 2.20 (dd, J = 11.2, 9.8 Hz, 1H), 0.99 (d, J = 6.3 Hz, 3H).13C NMR (101 MHz, DMSO-d6) δ 146.2, 145.8, 145.7, 143.2, 142.7, 142.0, 139.8, 137.5, 133.1, 130.1, 129.6, 126.5, 113.7, 57.6, 50.6, 50.4, 46.6, 45.8, 19.9. HRMS (ESI, m / z): calculated for C19H23N6 [M+H]+: 334.19059; found 335.19780. Purity (LC): 94% Example 88: Synthesis of tert-butyl 3- 4-yl)-3,8-diazabicyclo[3.2.1]octane-8- carboxylate Prepared using general procedure 1.1 using 3,4-dibromopyridine (500 mg, 2.1 mmol), tert- butyl 3,8-diazabicyclo[3.2.1]octane-8-carboxylate (896 mg, 4.2 mmol), and acetonitrile (2.6 mL).The crude material was purified using NP MPLC (EtOAc / Hex; 0-100%) to provide tert-butyl 3-(3-bromopyridin-4-yl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate as a low-melting white solid (184 mg, 0.5 mmol, 24% yield).1H NMR (400 MHz, DMSO-d6) δ 8.52 (s, 1H), 8.34 (d, J = 5.4 Hz, 1H), 7.08 (d, J = 5.5 Hz, 1H), 4.21 (s, 2H), 3.40 (d, J = 10.0 Hz, 2H), 2.89 (d, J = 11.3 Hz, 2H), 2.03 (d, J = 7.1 Hz, 2H), 1.87 – 1.76 (m, 2H), 1.42 (s, 9H).13C NMR (101 MHz, DMSO-d6) δ 155.8, 152.8, 152.6, 149.6, 116.5, 114.2, 79.0, 53.9 (broad, 2C), 28.1, 26.8 (broad). HRMS (ESI, m / z): calculated for C16H23N3O2Br [M+H]+: 368.09678; found 368.09653. Attorney Docket No.: 393976-00101 Example 89: Synthesis of 6-ylmethyl)amino)pyridin-4-yl)-3,8- diazabicyclo[3.2.1]octane-8-carboxylate Prepared using general procedure 1.2 using tert-butyl 3-(3-bromopyridin-4-yl)-3,8- diazabicyclo[3.2.1]octane-8-carboxylate (80 mg, 0.2 mmol), quinoxalin-6-ylmethanamine (86 mg, 0.5 mmol), Pd2dba3(4 mg, 0.004 mmol) BINAP (5 mg, 0.008 mmol), NaOtBu (42 mg, 0.4 mmol), and toluene (2 mL). The crude product was purified using RP MPLC (MeOH / 0.1% NH3 in H2O; 10-100%) followed by NP MPLC (MeOH / DCM; 0-15%) to yield tert-butyl (1R,5S)-3-(3- ((quinoxalin-6-ylmethyl)amino)pyridin-4-yl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate as a yellow residue (62 mg, 0.1 mmol, 64% yield).1H NMR (400 MHz, CD3OD) δ 8.83 (s, 2H), 8.08 (d, J = 8.7 Hz, 1H), 8.04 (d, J = 1.2 Hz, 1H), 7.89 (dd, J = 8.7, 1.9 Hz, 1H), 7.83 (d, J = 5.0 Hz, 1H), 7.77 (s, 1H), 4.71 (s, 1H), 4.34 (br s, 2H), 3.28 – 3.18 (m, 2H), 2.98 – 2.85 (m, 2H), 2.10 – 2.02 (m, 2H), 1.98 – 1.89 (m, 2H), 1.49 (s, 9H).13C NMR (101 MHz, CD3OD) δ 153.8, 146.2, 145.2, 144.9, 142.5, 142.5, 141.9, 139.4, 138.3, 132.1, 129.7, 129.1, 125.9, 114.5, 79.9, 54.2 (broad), 53.5 (broad), 47.0, 27.3, 27.0 (broad). HRMS (ESI, m / z): calculated for C25H31N6O2[M+H]+: 447.25028; found 447.25008. Example 90: Synthesis of [3.2.1]octan-3-yl)-N-(quinoxalin-6- ylmethyl)pyridin-3-amine Prepared using general procedure 1.3 tert-butyl (1R,5S)-3-(3-((quinoxalin-6- ylmethyl)amino)pyridin-4-yl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (34 mg, 0.08 mmol) in DCM (0.2 mL) and 2 M HCl in Et2O (0.2 mL, 0.08 mmol). The crude product was purified using RP MPLC (MeOH / 0.1% NH3 in H2O; 10-100%) to yield 4-((1R,5S)-3,8-diazabicyclo[3.2.1]octan- Attorney Docket No.: 393976-00101 3-yl)-N-(quinoxalin-6-ylmethyl)pyridin-3-amine as a yellow residue (4 mg, 0.11 mmol, 14% yield).1H NMR (400 MHz, CD3OD) δ 8.86 – 8.84 (m, 1H), 8.10 (d, J = 8.7 Hz, 1H), 8.06 (d, J = 1.2 Hz, 1H), 7.91 (dd, J = 8.7, 1.9 Hz, 1H), 7.84 (d, J = 5.3 Hz, 1H), 7.76 (s, 1H), 7.01 (d, J = 5.3 Hz, 1H), 4.73 (s, 2H), 3.61 (d, J = 1.6 Hz, 2H), 3.23 (dd, J = 11.8, 2.9 Hz, 2H), 2.94 (d, J = 10.7 Hz, 2H), 2.11 – 2.01 (m, 2H), 1.93 – 1.83 (m, 2H).13C NMR (101 MHz, CD3OD) δ 148.0, 146.7, 146.3, 143.97, 143.95, 143.3, 140.8, 139.7, 133.4, 131.2, 130.5, 127.3, 115.8, 56.3, 55.7, 48.42, 29.3. HRMS (ESI, m / z): calculated for C20H23N6[M+H]+: 347.19788; found 347.19751. Purity (LC): >99% Example 91: Synthesis of tert- 4-yl)-2,6-diazaspiro[3.3]heptane-2- carboxylate Prepared according to general procedure 2.1 using 4-chloro-3-nitropyridine (868 mg, 5.5 mmol), 2,6-diazaspiro[3.3]heptane-2-carboxylic acid, 1,1-dimethylethyl ester, ethanedioate (2:1) (4.0 g, 8.2 mmol), and triethylamine (3.3 g, 32.8 mmol), in THF (5.5 mL). The crude product was purified on NP MPLC (EtOAc / Hex; 0-100%) to afford tert-butyl 6-(3-nitropyridin-4-yl)-2,6- diazaspiro[3.3]heptane-2-carboxylate as a yellow solid (1.6 g, 5.0 mmol, 92% yield).1H NMR (400 MHz, DMSO-d6) δ 8.72 (s, 1H), 8.22 (d, J = 6.1 Hz, 1H), 6.62 (d, J = 6.1 Hz, 1H), 4.20 (s, 4H), 4.08 – 3.98 (br s, 4H), 1.37 (s, 9H).13C NMR (101 MHz, DMSO-d6) δ 155.3, 151.0, 147.4, 147.1, 132.2, 110.0, 78.6, 62.8, 32.1, 28.0, 20.7. Example 92: Synthesis of 6-(3- 2,6-diazaspiro[3.3]heptane-2-carboxylate Attorney Docket No.: 393976-00101 Prepared according to general procedure 2.2 using tert-butyl 6-(3-nitropyridin-4-yl)-2,6- diazaspiro[3.3]heptane-2-carboxylate (801 mg, 2.5 mmol), 10 wt.% Pd / C (27 mg, .03 mmol) and MeOH (25.0 mL). The crude product was purified on RP MPLC (MeOH / 0.1% NH3in H2O; 10- 100%) to afford tert-butyl 6-(3-aminopyridin-4-yl)-2,6-diazaspiro[3.3]heptane-2-carboxylate as a white solid (90 mg, 0.3 mmol, 12% yield). Example 93: Synthesis of 6-ylmethyl)amino)pyridin-4-yl)-2,6- diazaspiro[3.3]heptane-2-carboxylate Prepared according to general procedure 2.3 using tert-butyl 6-(3-aminopyridin-4-yl)-2,6- diazaspiro[3.3]heptane-2-carboxylate (172 mg, 0.6 mmol), quinoxaline-6-carbaldehyde (103 mg, 0.7 mmol), EtOH (5.9 mL), and NaBH4(67 mg, 1.8 mmol). Crude product was purified with RP MPLC (MeOH / 0.1% NH3 in H2O; 10-100%) to afford tert-butyl 6-(3-((quinoxalin-6- ylmethyl)amino)pyridin-4-yl)-2,6-diazaspiro[3.3]heptane-2-carboxylate as a yellow solid (101 mg, 0.2 mmol, 26% yield).1H NMR (400 MHz, DMSO-d6) δ 8.90 (q, J = 1.9 Hz, 2H), 8.10 – 8.01 (m, 2H), 7.89 (dd, J = 8.6, 1.9 Hz, 1H), 7.69 (d, J = 5.1 Hz, 1H), 7.55 (s, 1H), 6.37 (d, J = 5.2 Hz, 1H), 5.33 (t, J = 5.9 Hz, 1H), 4.58 (d, J = 5.8 Hz, 2H), 4.13 (s, 4H), 4.04 (s, 4H), 1.39 (s, 9H).13C NMR (101 MHz, DMSO-d6) δ 155.9, 146.1, 145.7, 143.1, 142.7, 141.9, 140.1, 133.7, 132.8, 130.3, 129.5, 126.8, 108.3, 79.1, 62.4, 49.1, 46.8, 33.3, 28.5. Example 94: Synthesis of -4-(2,6-diazaspiro[3.3]heptan-2- yl)pyridin-3-amine trifluoracetic acid salt Attorney Docket No.: 393976-00101 Prepared according to general procedure 2.4 using tert-butyl 6-(3-((quinoxalin-6- ylmethyl)amino)pyridin-4-yl)-2,6-diazaspiro[3.3]heptane-2-carboxylate (23 mg, 0.1 mmol), DCM (0.5 mL), and TFA (0.4 mL). The crude material was purified using RP MPLC (MeOH / 0.1% TFA in H2O; 10-100%) afforded N-(quinoxalin-6-ylmethyl)-4-(2,6-diazaspiro[3.3]heptan-2- yl)pyridin-3-amine trifluoroacetic acid salt as a red solid (18 mg, 0.1 mmol, quant.).1H NMR (400 MHz, DMSO-d6) δ 13.59 (s, 1H), 8.93 (d, J = 1.1 Hz, 2H), 8.14 – 8.04 (m, 2H), 7.95 – 7.87 (m, 2H), 7.50 (s, 1H), 6.59 (d, J = 6.6 Hz, 1H), 6.01 (s, 1H), 4.63 (s, 4H), 4.58 (s, 2H), 4.22 (t, J = 6.1 Hz, 4H).13C NMR (101 MHz, DMSO-d6) δ 159.0 (q, J = 33.7 Hz), 150.6, 146.3, 145.9, 142.6, 142.1, 141.2, 133.6, 133.1, 130.4, 129.7, 127.2, 120.8, 106.4, 63.1, 55.0, 46.8, 36.2. Example 95: Synthesis of 4- tetrahydropyrido[3,4-b]pyrazine 1,2,3,4-Tetrahydropyrido[3,4-b]pyrazine (250 mg, 1.9 mmol, 1.0 equiv) was added to an oven-dried 100 mL round bottom flask. Next, the flask was charged with DMF (7.4 mL) and triethylamine (281 mg, 2.8 mmol, 1.5 equiv). Then, 6-(bromomethyl)quinoxaline (413 mg, 1.9 mmol, 1.0 equiv) was added, and the solution was left to stir for 6 hours. 10 mL of ethyl acetate was added upon reaction completion, causing the reaction mixture to become turbid as solids crashed out. These solids were captured via vacuum filtration and washed with ethyl acetate. These solids were scratched off the filter paper, revealing 4-(quinoxalin-6-ylmethyl)-1,2,3,4- tetrahydropyrido[3,4-b]pyrazine (223 mg, 44% yield).1H NMR (400 MHz, DMSO-d6) δ 8.99 (s, 2H), 8.63 (s, 1H), 8.16 (d, J = 8.7 Hz, 1H), 8.08 (d, J = 2.0 Hz, 1H), 8.03 (dd, J = 6.8, 1.8 Hz, 1H), 7.82 (dd, J = 8.7, 2.0 Hz, 1H), 7.69 – 7.62 (m, 1H), 6.71 (d, J = 6.8 Hz, 1H), 6.46 (s, 1H), 5.61 (s, 2H), 3.43 (dd, J = 4.9, 2.8 Hz, 2H), 3.19 (td, J = 4.9, 2.0 Hz, 2H).13C NMR (101 MHz, DMSO- d6) δ 146.8, 146.8, 146.1, 142.4, 142.4, 138.4, 135.3, 131.7, 130.5, 130.1, 128.7, 122.7, 106.1, 59.9, 37.1, 36.2. HRMS (ESI, m / z): calculated for C14H21N3O2Br [M+H]+: 278.13275; found 278.14048. Attorney Docket No.: 393976-00101 Example 96: Synthesis of tert-Butyl 4-yl)amino)ethyl)carbamate Prepared according to 4-chloro-3-nitropyridine (321 mg, 2.0 mmol), tert-butyl (2-aminoethyl)carbamate (648 mg, 4.0 mmol), and triethylamine (614 mg, 6.1 mmol), in acetonitrile (4.0 mL). The crude product was purified with NP MPLC (EtOAc / Hex; 0- 100%) to afford tert-Butyl (2-((3-nitropyridin-4-yl)amino)ethyl)carbamate as a yellow solid (530 mg, 1.9 mmol, 93% yield).1H NMR (400 MHz, DMSO-d6) δ 9.01 (s, 1H), 8.47 (s, 1H), 8.26 (dd, J = 6.3, 0.8 Hz, 1H), 7.03 (d, J = 6.3 Hz, 1H), 3.44 (q, J = 6.1 Hz, 2H), 3.17 (q, J = 6.0 Hz, 2H), 1.35 (s, 9H). HRMS (ESI, m / z): calculated for C14H21N3O2Br [M+H]+: 283.13281; found 283.14032. Example 97: Synthesis of tert-butyl 4-yl)amino)ethyl)carbamate Prepared according to general procedure 2.2 using tert-butyl (2-((3-nitropyridin-4- yl)amino)ethyl)carbamate (530 mg, 1.9 mmol), 10 wt.% Pd / C (20 mg, .002 mmol) and MeOH (18.8 mL) to afford tert-butyl (2-((3-aminopyridin-4-yl)amino)ethyl)carbamate as a pale red oil (444 mg, 1.8 mmol, 94% yield) that was used in subsequent steps without further purification Example 98: Synthesis of 6-ylmethyl)amino)pyridin-4- yl)amino)ethyl)carbamate Prepared according to general procedure 2.3 using tert-butyl (2-((3-aminopyridin-4- yl)amino)ethyl)carbamate (58 mg, 0.2 mmol), quinoxaline-6-carbaldehyde (40 mg, 0.3 mmol), Attorney Docket No.: 393976-00101 EtOH (2.3 mL) and NaBH4 (26 mg, 0.7 mmol). The crude product was purified with RP MPLC (MeOH / 0.1% NH3 in H2O; 10-100%) to afford tert-butyl (2-((3-((quinoxalin-6- ylmethyl)amino)pyridin-4-yl)amino)ethyl)carbamate as a yellow solid (23 mg, 0.2 mmol, 26% yield).1H NMR (400 MHz, DMSO-d6) δ 8.93 – 8.87 (m, 2H), 8.08 (d, J = 8.7 Hz, 2H), 7.89 (dd, J = 8.6, 2.0 Hz, 1H), 7.64 (d, J = 5.3 Hz, 1H), 7.50 (s, 1H), 6.92 (s, 1H), 6.47 (d, J = 5.3 Hz, 1H), 4.59 (s, 2H), 3.38 (s, 1H), 3.23 – 3.09 (m, 6H), 1.38 (s, 9H).13C NMR (101 MHz, DMSO-d6) δ 171.5, 146.1, 145.6, 142.8, 142.7, 142.0, 140.8, 131.5, 130.9, 130.5, 129.5, 127.0, 126.6 103.8, 78.2, 48.4, 46.9, 42.5, 28.6. HRMS (ESI, m / z): calculated for C14H21N3O2Br [M+H]+: 395.21172; found 395.22018. Example 99: Synthesis of 6-ylmethyl)pyridine-3,4- diamine hydrochloride salt Prepared according to general procedure 2.4 using tert-butyl (2-((3-((quinoxalin-6- ylmethyl)amino)pyridin-4-yl)amino)ethyl)carbamate (23.4 mg, 0.01 mmol), 2 M HCl (0.8 mL) and DCM (0.6 mL) to afford N4-(2-aminoethyl)-N3-(quinoxalin-6-ylmethyl)pyridine-3,4-diamine hydrochloride salt as a yellow solid (19 mg, quant.).1H NMR (400 MHz, DMSO-d6) δ 13.86 (t, J = 6.1 Hz, 1H), 8.89 (q, J = 1.9 Hz, 2H), 8.55 (br s, 3H), 8.27 (d, J = 6.0 Hz, 1H), 8.10 – 8.02 (m, 2H), 7.91 (dd, J = 8.7, 1.9 Hz, 1H), 7.85 – 7.78 (m, 1H), 7.40 – 7.35 (m, 1H), 6.85 (dd, J = 6.7, 1.3 Hz, 1H), 4.66 (s, 2H), 3.66 (q, J = 5.5 Hz, 2H), 3.15 (q, J = 6.0 Hz, 2H).13C NMR (101 MHz, DMSO-d6) δ 147.6, 146.2, 145.8, 142.4, 141.9, 141.3, 132.8, 132.1, 130.5, 129.6, 127.0, 117.1, 103.0, 45.8, 40.7, 37.7. HRMS (ESI, m / z): calculated for C14H21N3O2Br [M+H]+: 295.15929; found 295.16710. Example 100: Synthesis of tert-butyl 4-yl)amino)propyl)carbamate Attorney Docket No.: 393976-00101 Prepared according to general procedure 2.1 using 4-chloro-3-nitropyridine (323 mg, 2.0 mmol), tert-butyl (3-aminopropyl)carbamate (533 mg, 3.1 mmol), triethylamine (0.4 mL, 3.0 mmol), and THF (2.7 mL). The crude product was purified on NP MPLC (EtOAc / Hex; 0-100%) to afford tert-butyl (3-((3-nitropyridin-4-yl)amino)propyl)carbamate as a yellow solid (451 mg, 1.5 mmol, 75% yield).1H NMR (400 MHz, DMSO-d6) δ 9.02 (s, 1H), 8.48 (s, 1H), 8.25 (dd, J = 6.3, 0.8 Hz, 1H), 6.99 (d, J = 6.3 Hz, 1H), 6.92 (s, 0H), 3.40 (q, J = 6.6 Hz, 2H), 3.00 (q, J = 6.3 Hz, 2H), 1.68 (p, J = 6.7 Hz, 2H), 1.37 (s, 9H).13C NMR (101 MHz, DMSO-d6) δ 156.2, 153.1, 148.8, 148.5, 129.8, 108.9, 78.0, 39.3, 37.6, 28.7, 28.7. HRMS (ESI, m / z): calculated for C14H21N3O2Br [M+H]+: 297.14846; found 297.15613. Example 101: Synthesis of tert-butyl 4-yl)amino)propyl)carbamate Prepared according to general procedure 2.2 using tert-butyl (3-((3-nitropyridin-4- yl)amino)propyl)carbamate (451 mg, 1.5 mmol), 10 wt.% Pd / C (16 mg, 0.002 mmol) and MeOH (15.2 mL) to afford tert-butyl (3-((3-aminopyridin-4-yl)amino)propyl)carbamate as a pale red oil (308 mg, 1.2 mmol, 76% yield) that was used in subsequent steps without further purification. Example 102: Synthesis 6-ylmethyl)amino)pyridin-4- yl)amino)propyl)carbamate Prepared according to general procedure 2.3 using tert-butyl (3-((3-aminopyridin-4- yl)amino)propyl)carbamate (308 mg, 1.2 mmol), quinoxaline-6-carbaldehyde (201 mg, 1.3 mmol), EtOH (11.6 mL) and NaBH4 (218 mg, 5.8 mmol). The crude product was purified on RP MPLC (MeOH / 0.1% NH3in H2O; 10-100%) to afford tert-butyl (3-((3-((quinoxalin-6- ylmethyl)amino)pyridin-4-yl)amino)propyl)carbamate as a dark yellow solid (60 mg, 0.2 mmol, Attorney Docket No.: 393976-00101 13% yield).1H NMR (400 MHz, CD3OD) δ 8.84 (s, 2H), 8.07 (d, J = 8.4 Hz, 2H), 7.96 – 7.89 (m, 1H), 7.68 (d, J = 5.6 Hz, 1H), 7.48 (s, 1H), 6.54 (d, J = 5.5 Hz, 1H), 4.65 (s, 2H), 3.27 (m, overlaps with solvent, 2H), 3.19 (t, J = 6.7 Hz, 2H), 1.86 (q, J = 6.8 Hz, 2H), 1.44 – 1.40 (m, 9H).13C NMR (101 MHz, CD3OD) δ 145.1, 144.7, 144.3, 142.7, 142.5, 141.9, 140.2, 140.1, 130.9, 130.3, 130.1, 128.8, 126.2, 103.5, 78.6, 39.8, 37.5, 28.7, 27.3. Example 103: Synthesis of 6-ylmethyl)pyridine-3,4- diamine hydrochloride Prepared according to general procedure 2.4 using tert-butyl (3-((3-((quinoxalin-6- ylmethyl)amino)pyridin-4-yl)amino)propyl)carbamate (60 mg, 0.2 mmol), 2 M HCl in ether (1.8 mL) and DCM (1.5 mL) to afforded N4-(3-aminopropyl)-N3-(quinoxalin-6-ylmethyl)pyridine- 3,4-diamine as a dark orange solid (40 mg, 0.2 mmol, quant.).1H NMR (400 MHz, CD3OD) δ 8.87 (s, 2H), 8.15 – 8.06 (m, 2H), 7.94 (dd, J = 8.7, 2.0 Hz, 1H), 7.82 (dd, J = 6.7, 1.2 Hz, 1H), 7.43 (d, J = 1.2 Hz, 1H), 6.91 (d, J = 6.7 Hz, 1H), 4.74 (s, 2H), 3.58 (t, J = 7.0 Hz, 2H), 3.18 – 3.10 (m, 2H), 2.20 – 2.08 (m, 2H).13C NMR (101 MHz, DMSO-d6) δ 146.7, 146.3, 145.9, 142.6, 142.0, 141.6, 133.3, 132.2, 130.4, 129.7, 127.1, 119.0, 102.9, 46.0, 40.2, 37.2, 26.1. HRMS (ESI, m / z): calculated for C14H21N3O2Br [M+H]+: 309.17494; found 309.18250. Example 104: Synthesis of tert-butyl 4- 4-yl)piperazine-1-carboxylate Prepared using the general procedure 1.1 using 2,4-dibromopyridine (1.0 g, 4.2 mmol), tert-butyl piperazine-1-carboxylate (2.0 g, 10.6 mmol), and acetonitrile (5.3 mL). The crude material was purified using NP MPLC (EtOAc / Hex; 0-100%) to provide tert-butyl 4-(2- bromopyridin-4-yl)piperazine-1-carboxylate as a low-melting white solid (290 mg, 0.8 mmol, Attorney Docket No.: 393976-00101 20% yield).1H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 6.3 Hz, 1H), 6.84 (d, J = 2.4 Hz, 1H), 6.66 (dd, J = 6.3, 2.4 Hz, 1H), 3.62 – 3.55 (m, 4H), 3.45 – 3.37 (m, 4H), 1.48 (s, 9H).13C NMR (101 MHz, CDCl3) δ 156.2, 154.5, 150.0, 143.6, 111.3, 107.9, 80.4, 47.9, 45.8, 42.8 (broad), 28.4. HRMS (ESI, m / z): calculated for C14H21N3O2Br [M+H]+: 342.08118; found 342.08047. Example 105: Synthesis of 6-ylmethyl)amino)pyridin-4- yl)piperazine-1-carboxylate Prepared using general procedure 1.2 using tert-butyl 4-(2-bromopyridin-4-yl)piperazine- 1-carboxylate (150 mg, 0.4 mmol), quinoxalin-6-ylmethanamine (174 mg, 1.1 mmol), Pd2dba3(8 mg, 0.09 mmol) BINAP (11 mg, 0.18 mmol), NaOtBu (84 mg, 0.9 mmol), and toluene (4 mL). The crude product was purified using RP MPLC (MeOH / 0.1% NH3 in H2O; 10-100%) followed by NP MPLC (MeOH / DCM; 0-15%) to yield tert-butyl 4-(2-((quinoxalin-6- ylmethyl)amino)pyridin-4-yl)piperazine-1-carboxylate as a yellow residue (12 mg, 0.007 mmol, 7% yield).1H NMR (400 MHz, CD3OD) δ 8.83 (s, 2H), 8.09 – 8.00 (m, 2H), 7.86 (dd, J = 8.7, 1.9 Hz, 1H), 7.64 (d, J = 6.3 Hz, 1H), 6.26 (dd, J = 6.4, 2.3 Hz, 1H), 5.96 (d, J = 2.2 Hz, 1H), 4.75 (s, 2H), 3.54 – 3.46 (m, 4H), 3.29 – 3.23 (m, 4H), 1.47 (s, 9H).13C NMR (101 MHz, CD3OD) δ 159.4, 156.9, 154.9, 146.2, 145.0, 144.6, 143.5, 142.5, 141.8, 130.0, 128.6, 125.7, 100.8, 90.4, 80.1, 45.7, 44.7, 42.8 (broad), 27.2. HRMS (ESI, m / z): calculated for C23H29N6O2[M+H]+]+: 421.23468; found 421.23476. Example 106: Synthesis of 4- 6-ylmethyl)pyridin-2-amine Attorney Docket No.: 393976-00101 Prepared using general procedure 1.3 using tert-butyl 4-(2-((quinoxalin-6- ylmethyl)amino)pyridin-4-yl)piperazine-1-carboxylate (12 mg, 0.03 mmol) in DCM (0.6 mL) and 2 M HCl in Et2O (0.07 mL, 2.9 mmol). The crude product was purified using RP MPLC (MeOH / 0.1% NH3 in H2O; 10-100%) to yield 4-(piperazin-1-yl)-N-(quinoxalin-6- ylmethyl)pyridin-2-amine as a pale yellow residue (1 mg, 0.03 mmol, 10% yield).1H NMR (400 MHz, CD3OD) δ 8.83 (s, 2H), 8.06 (d, J = 8.8 Hz, 1H), 8.03 (d, J = 1.2 Hz, 1H), 7.87 (dd, J = 8.7, 1.9 Hz, 1H), 7.64 (d, J = 6.3 Hz, 1H), 6.25 (dd, J = 6.4, 2.3 Hz, 1H), 5.95 (d, J = 2.2 Hz, 1H), 4.74 (s, 2H), 3.27 – 3.19 (m, 4H), 2.91 – 2.84 (m, 4H).13C NMR (101 MHz, CD3OD) δ 161.2, 158.8, 148.1, 146.4, 146.0, 145.2, 143.9, 143.2, 131.5, 130.0, 127.1, 102.1, 91.8, 47.9, 46.11, 46.08. HRMS (ESI, m / z): calculated for C18H21N6[M+H]+: 321.18218; found 321.18199. Purity (LC): >99% Example 107: Synthesis of tert-butyl 4- 2-yl)piperazine-1-carboxylate Prepared using the general procedure 1.1 using 2,4-dibromopyridine (1.0 g, 4.2 mmol), tert-butyl piperazine-1-carboxylate (2.0 g, 10.6 mmol), and acetonitrile (5.3 mL). The crude material was purified using NP MPLC (EtOAc / Hex; 0-100%) to provide tert-butyl 4-(4- bromopyridin-2-yl)piperazine-1-carboxylate as a white solid (272 mg, 19% yield).1H NMR (400 MHz, CDCl3) δ 7.98 (dd, J = 5.2, 0.4 Hz, 1H), 6.81 – 6.72 (m, 2H), 3.52 (s, 8H), 1.47 (s, J = 7.6 Hz, 9H).13C NMR (101 MHz, CDCl3) δ 159.7, 154.9, 148.5, 134.2, 116.7, 110.1, 80.2, 45.0, 43.3 (broad), 28.5. HRMS (ESI, m / z): calculated for C14H21N3O2Br [M+H]+: 342.08118; found 342.08060. Attorney Docket No.: 393976-00101 Example 108: Synthesis of tert-butyl 4-(2-((quinoxalin-6-ylmethyl)amino)pyridin-4- yl)piperazine-1-carboxylate Prepared using general procedure 1.2 using tert-butyl 4-(4-bromopyridin-2-yl)piperazine- 1-carboxylate (150 mg, 0.4 mmol), quinoxalin-6-ylmethanamine (105 mg, 0.7 mmol), Pd2dba3 (8 mg, 0.09 mmol) BINAP (11 mg, 0.18 mmol), NaOtBu (84 mg, 0.9 mmol), and toluene (4 mL). The crude product was purified using RP MPLC (MeOH / 0.1% NH3in H2O; 10-100%) followed by NP MPLC (MeOH / DCM; 0-15%) to yield tert-butyl 4-(2-((quinoxalin-6- ylmethyl)amino)pyridin-4-yl)piperazine-1-carboxylate as a yellow residue (111 mg, 0.2 mmol, 60% yield).1H NMR (400 MHz, CDCl3) δ 8.84 (s, 2H), 8.11 (d, J = 8.7 Hz, 1H), 8.04 (d, J = 1.2 Hz, 1H), 7.85 (d, J = 5.8 Hz, 1H), 7.75 (dd, J = 8.7, 1.9 Hz, 1H), 6.05 (dd, J = 5.8, 1.9 Hz, 1H), 5.80 (d, J = 1.8 Hz, 1H), 4.87 (br s, 1H), 4.63 (d, J = 5.8 Hz, 2H), 3.53 – 3.45 (m, 4H), 3.45 – 3.35 (m, 4H), 1.46 (s, 9H).13C NMR (101 MHz, CD3OD) δ 161.8, 157.4, 156.3, 147.7, 146.6, 146.2, 143.8, 143.7, 143.2, 131.1, 130.3, 127.3, 102.5, 91.2, 81.3, 47.1, 46.8, 44.5 (broad), 28.6. HRMS (ESI, m / z): calculated for C23H29N6O2 [M+H]+: 421.23468; found 421.23449. Example 109: Synthesis of 6-ylmethyl)amino)pyridin-2- yl)piperazine-1-carboxylate Prepared using general procedure 1.3 using tert-butyl 4-(4-((quinoxalin-6- ylmethyl)amino)pyridin-2-yl)piperazine-1-carboxylate (90 mg, 0.2 mmol) in DCM (4.3 mL) and 2 M HCl in Et2O (0.1 mL, 4.3 mmol). The crude product was purified using RP MPLC (MeOH / 0.1% NH3in H2O; 10-100%) to yield 2-(piperazin-1-yl)-N-(quinoxalin-6- ylmethyl)pyridin-4-amine as a pale yellow residue (33 mg, 0.1 mmol, 48% yield).1H NMR (400 MHz, CD3OD) δ 8.85 (s, 2H), 8.08 (d, J = 8.7 Hz, 1H), 8.03 (d, J = 1.2 Hz, 1H), 7.86 (dd, J = 8.7, 1.9 Hz, 1H), 7.66 (d, J = 6.0 Hz, 1H), 6.13 (dd, J = 6.0, 2.0 Hz, 1H), 5.92 (d, J = 1.9 Hz, 1H), 4.66 (s, 2H), 3.31 – 3.26 (m, 4H), 2.89 – 2.83 (m, 4H).13C NMR (101 MHz, CD3OD) δ 162.6, 157.4, Attorney Docket No.: 393976-00101 148.1, 146.6, 146.2, 144.0, 143.9, 143.3, 131.2, 130.3, 127.3, 102.4, 91.1, 47.8, 46.8, 46.2. HRMS (ESI, m / z): calculated for C18H21N6 [M+H]+: 321.18218; found 321.18192. Purity (LC): 96% Example 110: Synthesis of tert- 3-yl)piperazine-1-carboxylate Prepared according to general 3-bromo-4-nitropyridine (600 mg, 3.0 mmol), triethylamine (1.2 mL, 8.9 mmol), and acetonitrile (3.0 mL). The crude product was purified with NP MPLC (EtOAc / Hex; 0-100%) to afford tert-butyl 4-(4-nitropyridin-3- yl)piperazine-1-carboxylate as a red solid (410 mg, 1.3 mmol, 45% yield).1H NMR (400 MHz, CDCl3) δ 8.57 (s, 1H), 8.38 (d, J = 5.2 Hz, 1H), 7.54 (d, J = 5.2 Hz, 1H), 3.61 – 3.54 (m, 4H), 3.10 (m, 4H), 1.46 (s, 9H).13C NMR (101 MHz, CDCl3) δ 154.6, 147.5, 145.1, 143.8, 139.3, 117.6, 80.2, 51.2, 43.6 (br s), 28.4. HRMS (ESI, m / z): calculated for C18H21N6 [M+H]+: 309.14846; found 309.15599. Example 111: Synthesis of tert-butyl 3-yl)piperazine-1-carboxylate Prepared according to general procedure 2.2 using tert-butyl 4-(4-nitropyridin-3- yl)piperazine-1-carboxylate (350 mg, 1.1 mmol), 10wt% Pd / C (12 mg, 0.01 mmol) and MeOH (11.4 mL). The crude product was purified with (RP MPLC MeOH / 0.1% NH3in H2O; 10-100%) to afford tert-butyl 4-(4-aminopyridin-3-yl)piperazine-1-carboxylate as a deep orange solid (110 mg, 0.4 mmol, 35%).1H NMR (400 MHz, DMSO-d6) δ 7.89 (s, 1H), 7.81 (d, J = 5.3 Hz, 1H), 6.55 (d, J = 5.4 Hz, 1H), 5.66 (s, 2H), 3.47 (br s, 4H), 2.77 (t, J = 5.0 Hz, 4H), 1.42 (s, 9H).13C NMR (101 MHz, DMSO-d6) δ 154.3, 148.8, 145.8, 141.2, 134.1, 109.1, 79.3, 50.8, 44.5 (br s), 28.5. HRMS (ESI, m / z): calculated for C18H21N6 [M+H]+: 279.17428; found 279.18198. Attorney Docket No.: 393976-00101 Example 112: Synthesis of tert- 3-yl)piperazine-1-carboxylate tert-Butyl 4-(4-aminopyridin-3-yl)piperazine-1-carboxylate (24.8 mg, 89.1 umol, 1.0 equiv) was added to a flame dried 25 mL round bottom flask with a stir bar. The flask was capped with a septum, and a Schlenk line was used to replace the atmosphere with argon. The reaction was then charged with dry THF (840 uL) and cooled to -78 °C with a dry ice / acetone bath. After allowing the reaction mixture to cool, a solution of nBuLi in THF (78 uL, 1.07M) was added dropwise. After allowing the reaction to stir for a few minutes, 6-(bromomethyl)quinoxaline (18.6 mg, 83.4 umol, 1.0 equiv) in THF (167 uL) was added dropwise. The reaction was left to stir for 30 minutes and quenched with 50 mL of a sat. ammonium chloride solution. The organic material was extracted into ethyl acetate, loaded onto celite, and purified via NP MPLC (MeOH / DCM; 0- 20%) to afford tert-butyl 4-(4-aminopyridin-3-yl)piperazine-1-carboxylate (29.8 mg, 70.9 umol, 85% yield).1H NMR (400 MHz, DMSO-d6) δ 8.99 (s, 2H), 8.45 (d, J = 1.7 Hz, 1H), 8.30 (dd, J = 7.1, 1.6 Hz, 1H), 8.18 – 8.08 (m, 2H), 7.90 (dd, J = 8.7, 2.0 Hz, 1H), 7.42 (s, 1H), 6.95 (d, J = 7.0 Hz, 1H), 5.66 (s, 2H), 3.53 (br s, 4H), 2.80 (t, J = 5.0 Hz, 4H), 1.42 (s, 9H).13C NMR (101 MHz, DMSO-d6) δ 154.6, 154.1, 146.8, 146.8, 142.5, 142.4, 140.4, 138.2, 135.5, 134.8, 130.5, 130.2, 128.8, 109.6, 79.5, 59.9, 50.6, 28.5. HRMS (ESI, m / z): calculated for C18H21N6 [M+H]+: 279.17428; found 279.18198. Attorney Docket No.: 393976-00101 Example 113: Synthesis of 3-(piperazin-1-yl)-N-(quinoxalin-6-ylmethyl)pyridin-4-amine hydrochloride salt Prepared according to general procedure 2.4 using tert-butyl 4-(4-aminopyridin-3- yl)piperazine-1-carboxylate (20.0 mg, 0.05 mmol), 2 M HCl in ether (0.3 mL), and DCM (0.5 mL). Upon reaction completion, the reaction mixture was concentrated under a stream of nitrogen gas to afford 3-(piperazin-1-yl)-N-(quinoxalin-6-ylmethyl)pyridin-4-amine hydrochloride salt as a yellow solid (14 mg, 0.04 mmol, 94% yield).1H NMR (401 MHz, DMSO-d6) δ 9.49 (s, 2H), 8.95 (s, 2H), 8.60 (s, 1H), 8.50 (d, J = 1.6 Hz, 1H), 8.28 (dd, J = 7.1, 1.6 Hz, 1H), 8.16 – 8.04 (m, 2H), 7.87 (dd, J = 8.7, 2.0 Hz, 1H), 7.56 (s, 1H), 6.96 (d, J = 7.0 Hz, 1H), 5.67 (s, 2H), 3.25 (m, 4H), 3.05 (m, 4H).13C NMR (101 MHz, DMSO-d6) δ 154.6, 146.8, 146.8, 142.4, 142.4, 140.6, 138.4, 135.3, 133.9, 130.4, 130.2, 128.7, 109.8, 59.8, 47.5, 43.0. HRMS (ESI, m / z): calculated for C24H31N6O2 [M+H]+: 421.22737; found 421.23490. Example 114: Synthesis of tert-butyl 4- 4-yl)-1,4-diazepane-1-carboxylate Prepared using general procedure 1.1 using 3,4-dibromopyridine (800 mg, 3.4 mmol), tert- butyl 1,4-diazepane-1-carboxylate (812 mg, 4.1 mmol), and acetonitrile (4.2 mL). The crude material was purified using NP MPLC (EtOAc / Hex; 0-50%) to provide tert-butyl 4-(2- bromopyridin-4-yl)-1,4-diazepane-1-carboxylate as a white residue (129 mg, 0.3 mmol, 11% yield).1H NMR (400 MHz, CDCl3) mixture of rotamers: δ 7.98 (d, J = 6.3 Hz, 1H), 6.74 – 6.68 (m, 1H), 6.59 – 6.46 (m, 1H), 3.64 – 3.53 (m, 6H), 3.37 and 3.29 (two t, rotamers, J = 5.7 Hz, J = 5.9 Hz, 2H), 1.99 – 1.87 (m, 2H), 1.41 and 1.38 (two s, rotamers, 9H).13C NMR (101 MHz, CDCl3) mixture of rotamers, observed resonances for minor rotamer are enclosed in parentheses (): δ 155.0, (154.6), 153.9, 149.6, 143.2, 109.3, (109.1), 106.1, 80.0, (79.9), 49.8, (49.6), 48.6, (47.8), 46.13, (46.11), 45.7, 28.3, (28.2), 24.5, (24.2). HRMS (ESI, m / z): calculated for C15H23N3O2Br [M+H]+: 356.09678; found 356.09607. Attorney Docket No.: 393976-00101 Example 115: Synthesis of 6-ylmethyl)amino)pyridin-4-yl)-1,4- diazepane-1-carboxylate Prepared using general procedure 1.2 using tert-butyl 4-(2-bromopyridin-4-yl)-1,4- diazepane-1-carboxylate (150 mg, 0.4 mmol), quinoxalin-6-ylmethanamine (134 mg, 0.8 mmol), Pd2dba3(16 mg, 0.02 mmol) BINAP (22 mg, 0.04 mmol), NaOtBu (81 mg, 0.8 mmol), and toluene (3.8 mL). The crude product was purified RP MPLC (MeCN / 0.1% NH3 in H2O; 10-100%) followed by RP MPLC (MeCN / 0.1% CHCO2H in H2O; 10-100%) to yield tert-butyl 4-(2- ((quinoxalin-6-ylmethyl)amino)pyridin-4-yl)-1,4-diazepane-1-carboxylate as a brown residue (47 mg, 0.1 mmol, 26% yield).1H NMR (400 MHz, CD3OD) mixture of rotamers: δ 8.88 and 8.87 (two s, rotamers, 2H), 8.35 (br s, 2H), 8.14 – 8.06 (m, 2H), 7.94 – 7.85 (m, 1H) 7.57 and 7.53 (d, J = 7.5 Hz, J = 7.5 Hz, 1H)), 6.53 – 6.41 (m, 1H), 5.87 – 5.80 (m, 1H), 4.79 (s, 2H), 1.66 (br s, 2H), 1.25 and 1.22 (two s, rotamers, 9H).13C NMR (101 MHz, CD3OD) mixture of rotamers, resonances for minor rotamer are enclosed in parentheses ():δ 158.00, (157.92), 156.53, (156.29), 154.37, (154.26), 146.92, 146.58, 143.93, (143.91), 143.42, 141.85, (141.64), 137.22, (137.14), 130.96, (130.88), 130.82, 127.88, (127.73), 101.64, 87.45, 81.27, (81.11), 50.65, (50.48), 50.32, (50.20), 47.41, 46.45, 46.15, 40.44, 28.45, (28.39), 25.30 (broad). HRMS (ESI, m / z): calculated for C24H31N6O2[M+H]+: 435.25028; found 435.24911. Example 116: Synthesis of 4- 6-ylmethyl)pyridin-2-amine Prepared using general procedure 1.3 using tert-butyl 4-(2-((quinoxalin-6- ylmethyl)amino)pyridin-4-yl)-1,4-diazepane-1-carboxylate (47 mg, 0.11 mmol). in DCM (11 mL) Attorney Docket No.: 393976-00101 and 2 M HCl in Et2O (0.54 mL, 1.6 mmol). The crude product was purified using RP MPLC (MeCN / 0.1% NH3 in H2O; 10-100%) to provide 4-(1,4-diazepan-1-yl)-N-(quinoxalin-6- ylmethyl)pyridin-2-amine as an orange residue (17 mg, 0.05 mmol, 47% yield).1H NMR (400 MHz, CD3OD) δ 8.98 (app s, 1H), 8.19 (d, J = 8.7 Hz, 1H), 8.15 (s, 1H), 7.97 (dd, J = 8.7, 1.9 Hz, 1H), 7.64 (d, J = 7.6 Hz, 1H), 6.61 (d, J = 7.6 Hz, 1H), 3.97 – 3.91 (m, 1H), 3.71 (t, J = 5.9 Hz, 1H), 3.41 – 3.36 (m, 1H), 3.28 (s, 1H), 2.20 – 2.13 (m, 1H).13C NMR (101 MHz, CD3OD) δ 158.6, 154.1, 145.5, 145.5, 143.7, 141.9, 141.8, 137.3, 132.8, 129.6, 126.2, 102.2, 88.5, 48.8, 46.5, 46.4, 46.2, 46.1, 25.7. Peak at 48.8 ppm identified via HSQC. HRMS (ESI, m / z): calculated for C19H23N6[M+H]+: 335.19788; found 335.19699. Purity (LC): 95% Example 117: Synthesis of tert-butyl 4-yl)amino)ethyl)carbamate Prepared using general procedure 1.1 using 2,4-dibromopyridine (1 g, 4.0 mmol), tert-butyl (2-aminoethyl)carbamate (1 g, 8.0 mmol), and acetonitrile (10.0 mL). The crude material was purified using NP MPLC (EtOAc / Hex; 0-50%) to yield tert-butyl (2-((2-bromopyridin-4- yl)amino)ethyl)carbamate as a white residue (154 mg, 0.1 mmol, 10 % yield).1H NMR (400 MHz, CD3OD) δ 7.72 (d, J = 6.0 Hz, 1H), 6.70 (d, J = 2.2 Hz, 1H), 6.52 (dd, J = 6.0, 2.2 Hz, 1H), 3.26 – 3.14 (m, 4H), 1.39 (s, 9H).13C NMR (101 MHz, CDCl3) δ 157.2, 155.0, 149.5, 143.0, 109.6, 107.5, 80.2, 44.3, 39.6, 28.3. HRMS (ESI, m / z): calculated for C12H19N3O2Br [M+H]+: 315.06; found 316.06552; found 316.06573. Example 118: Synthesis of 6-ylmethyl)amino)pyridin-4- yl)amino)ethyl)carbamate Prepared using general procedure 1.2 using (2-((2-bromopyridin-4- yl)amino)ethyl)carbamate (154 mg, 0.5 mmol), quinoxalin-6-ylmethanamine (155 mg, 1.0 mmol), Pd2dba3(18 mg, 0.02 mmol), and BINAP (30 mg, 0.05 mmol μmol), NaOtBu (140 mg, 1.5 mmol), Attorney Docket No.: 393976-00101 and toluene (4.4 mL). The crude material was purified using RP MPLC (MeOH / 0.1% NH3 in H2O; 10-100%) to yield tert-butyl (2-((2-((quinoxalin-6-ylmethyl)amino)pyridin-4- yl)amino)ethyl)carbamate as a yellow residue (12 mg, 0.03 mmol, 6% yield).1H NMR (400 MHz, CD3OD) δ 8.85 – 8.78 (m, 2H), 8.03 (d, J = 8.8 Hz, 2H), 7.85 (dd, J = 8.6, 2.0 Hz, 1H), 7.51 – 7.45 (m, 1H), 5.95 (dd, J = 6.1, 2.1 Hz, 1H), 5.73 – 5.69 (m, 1H), 4.69 (s, 2H), 3.12 (d, J = 2.5 Hz, 4H), 1.42 – 1.35 (m, 9H).13C NMR (101 MHz, CD3OD) δ 159.4, 155.8, 145.90, 145.0, 144.5, 143.7, 142.5, 141.8, 130.0, 128.5, 125.7, 100.5, 87.4, 78.7, 44.8, 41.8, 39.0, 27.3. HRMS (ESI, m / z): calculated for C21H27N6O2 [M+H]+: 395.21899; found 395.21892. Example 119: Synthesis of (quinoxalin-6-ylmethyl)pyridine-2,4- diamine Prepared using general procedure 1.3 using tert-butyl (2-((2-((quinoxalin-6- ylmethyl)amino)pyridin-4-yl)amino)ethyl)carbamate (10 mg, 0.03 mmol) and 2 M HCl in Et2O (0.13 mL). A few drops of DCM were added when the solvent evaporated off. The crude material was purified using RP MPLC (MeOH / 0.1% NH3 in H2O; 10-100%). Fractions containing the desired product were combined and triturated with hexanes then water and blown down under a stream of nitrogen to yield N4-(2-aminoethyl)-N2-(quinoxalin-6-ylmethyl)pyridine-2,4-diamine as a yellow residue (2 mg, 0.009 mmol, 29% yield).1H NMR (400 MHz, CD3OD) δ 8.81 (s, 2H), 8.07 – 7.99 (m, 2H), 7.85 (dd, J = 8.7, 2.0 Hz, 1H), 7.49 (d, J = 6.1 Hz, 1H), 5.96 (dt, J = 6.1, 1.1 Hz, 1H), 5.73 – 5.63 (m, 1H), 4.69 (s, 2H), 3.11 (t, 2H), 2.73 (t, J = 6.2 Hz, 2H).13C NMR (100 MHz, CD3OD) δ 159.0, 156.0, 145.3, 145.1, 144.6, 143.5, 142.5, 141.8, 129.9, 128.6, 125.7, 100.7, 53.4, 44.8, 43.9, 39.8. HRMS (ESI, m / z): calculated for C16H19N6 [M+H]+: 295.16657; found 295.16665. Purity (LC): 95% Attorney Docket No.: 393976-00101 Example 120: Synthesis of tert-butyl 4- piperazine-1-carboxylate Prepared using general procedure dibromobenzene (0.08 mL, 0.6 mmol), tert- butyl piperazine-1-carboxylate (178 mg, 1.0 mmol), Pd2dba3(29 mg, 0.03 mmol), BINAP (30 mg, 0.05 mmol), NaOtBu (122 mg, 1.3 mmol), and toluene (1.6 mL). The crude material was purified using NP MPLC (EtOAc / Hex; 0-100%) to yield tert-butyl 4-(2-bromophenyl)piperazine-1- carboxylate as a white amorphous solid (120 mg, 0.3 mmol, 55% yield).1H NMR (400 MHz, CD3OD) δ 7.56 (dd, J = 7.9, 1.5 Hz, 1H), 7.33 – 7.27 (m, 1H), 7.12 (dd, J = 8.0, 1.6 Hz, 1H), 6.95 (ddd, J = 7.9, 7.3, 1.6 Hz, 1H), 3.58 (t, J = 5.1 Hz, 4H), 2.99 – 2.92 (m, 4H), 1.48 (s, 9H).13C NMR (100 MHz, CD3OD) δ 155.1, 150.4, 133.4, 128.2, 124.6, 121.1, 119.6, 79.9, 51.4, 44.2, 43.3, 27.3. HRMS (ESI, m / z): calculated for C15H22N2O2Br [M+H]+: 341.08592; found 341.08595. Example 121: Synthesis of tert- amino)phenyl)piperazine-1- carboxylate Prepared using general procedure 1.2 using tert-butyl 4-(2-bromophenyl)piperazine-1- carboxylate (120 mg, 0.4 mmol), quinoxalin-6-ylmethanamine (112 mg, 0.7 mmol), Pd2dba3 (13 mg, 0.01 mmol), BINAP (22 mg, 0.04 mmol), NaOtBu (101 mg, 1.1 mmol), and toluene (3.2 mL). The crude material was purified using RP MPLC (MeOH / 0.1% NH3in H2O; 10-100%) to yield tert-butyl 4-(2-((quinoxalin-6-ylmethyl)amino)phenyl)piperazine-1-carboxylate as a yellow residue (35 mg, 0.1 mmol, 24% yield).1H NMR (400 MHz, CD3OD) δ 8.88 – 8.67 (m, 2H), 8.08 – 7.93 (m, 2H), 7.89 – 7.79 (m, 1H), 7.03 – 6.95 (m, 1H), 6.87 – 6.78 (m, 1H), 6.61 – 6.54 (m, 1H), 6.54 – 6.42 (m, 1H), 4.63 (s, 2H), 3.73 – 3.38 (m, 4H), 2.96 – 2.69 (m, 4H), 1.46 (s, 9H).13C NMR (101 MHz, CD3OD) δ 145.0, 144.6, 129.8, 128.6, 125.5, 124.9, 119.5, 116.9, 110.5, 79.9, Attorney Docket No.: 393976-00101 51.3, 48.4, 46.8, 29.3, 27.3. HRMS (ESI, m / z): calculated for C24H30N5O2 [M+H]+: 420.23941; found 420.23920. Example 122: Synthesis of 2- 6-ylmethyl)aniline Prepared using 1.3 using 4-(2-((quinoxalin-6- ylmethyl)amino)phenyl)piperazine-1-carboxylate (35 mg, 0.08 mmol) and 2 M HCl in Et2O (0.4 mL). The crude material was purified using RP MPLC (MeOH / 0.1% NH3in H2O; 10-100%) to yield 2-(piperazin-1-yl)-N-(quinoxalin-6-ylmethyl)aniline (4 mg, 0.01 mmol, 13% yield).1H NMR (400 MHz, DMSO-d6) δ 8.86 (s, 2H), 8.04 (d, J = 8.6 Hz, 1H), 7.93 (d, J = 1.8 Hz, 1H), 7.83 (dd, J = 8.7, 1.9 Hz, 1H), 6.93 (dd, J = 7.7, 1.5 Hz, 1H), 6.75 (td, J = 7.6, 1.5 Hz, 1H), 6.52 (td, J = 7.6, 1.5 Hz, 1H), 6.40 (dd, J = 8.0, 1.4 Hz, 1H), 5.80 (t, J = 6.2 Hz, 1H), 4.60 (d, J = 6.0 Hz, 2H), 2.91 – 2.84 (m, 4H), 2.80 – 2.69 (m, 4H).13C NMR (101 MHz, DMSO-d6) δ 146.1, 145.6, 143.8, 142.7, 142.6, 141.9, 139.8, 130.1, 129.5, 126.3, 124.7, 119.7, 116.8, 110.5, 53.0, 46.9, 46.6, 29.4. HRMS (ESI, m / z): calculated for C19H22N5[M+H]+: 320.186976; found 320.18694. Purity (LC): 97% Example 123: Synthesis of tert-butyl (1- piperidin-4-yl)carbamate Prepared using general procedure 1.2 using 1,2-dibromobenzene (299 mg, 1.3 mmol), tert- butyl piperidin-4-ylcarbamate (381 mg, 1.9 mmol), Pd2dba3 (58 mg, 0.06 mmol), BINAP (59 mg, 0.1 mmol), NaOtBu (146 mg, 1.5 mmol), and toluene (3.2 mL). The crude material was purified with NP MPLC (EtOAc / Hex; 0-100%) to yield tert-butyl (1-(2-bromophenyl)piperidin-4- yl)carbamate as a white amorphous solid (150 mg, 0.6 mmol, 33% yield).1H NMR (400 MHz, CD3OD) δ 7.51 (dd, J = 7.9, 1.5 Hz, 1H), 7.25 (ddd, J = 8.0, 7.3, 1.5 Hz, 1H), 7.10 (dd, J = 8.0, 1.6 Hz, 1H), 6.88 (ddd, J = 8.0, 7.3, 1.6 Hz, 1H), 3.48 – 3.43 (m, 1H), 3.30 – 3.20 (m, 2H), 2.70 Attorney Docket No.: 393976-00101 (td, J = 11.6, 2.4 Hz, 2H), 1.96 – 1.87 (m, 2H), 1.65 (dtd, J = 12.5, 11.1, 3.8 Hz, 2H), 1.43 (s, 9H).13C NMR (100 MHz, CDCl3) δ 155.2, 151.0, 133.7, 128.2, 124.2, 121.0, 120.1, 79.3, 51.1, 47.6, 32.9, 28.4. HRMS (ESI, m / z): calculated for C16H24N2O2Br [M+H]+: 355.10157; found 355.10239. Example 124: butyl (4-(2-((quinoxalin-6- ylmethyl)amino)phenyl)cyclohexyl)carbamate Prepared using general method 1.2 using tert-butyl (4-(2- bromophenyl)cyclohexyl)carbamate (150 mg, 0.4 mmol), quinoxalin-6-ylmethanamine (102 mg, 0.6 mmol), Pd2dba3(16 mg, 0.02 mmol), BINAP (26 mg, 0.04 mmol), NaOtBu (122 mg, 1.3 mmol), and toluene (3.9 mL). The crude material was purified using RP MPLC (MeOH / 0.1% NH3in H2O; 10-100%) then NP MPLC (EtOAc / Hex; 0-100%) to yield tert-butyl (4-(2-((quinoxalin-6- ylmethyl)amino)phenyl)cyclohexyl)carbamate as a yellow residue (31 mg, 0.1 mmol, 17 % yield).1H NMR (400 MHz, CDCl3) δ 8.83 – 8.76 (m, 2H), 8.11 – 8.03 (m, 2H), 7.78 (dd, J = 8.7, 2.0 Hz, 1H), 7.02 (dd, J = 7.8, 1.4 Hz, 1H), 6.92 (td, J = 7.6, 1.4 Hz, 1H), 6.68 (td, J = 7.6, 1.4 Hz, 1H), 6.53 (dd, J = 8.0, 1.4 Hz, 1H), 5.31 (s, 1H), 4.59 (s, 2H), 4.50 (s, 1H), 3.63 – 3.59 (m, 1H), 3.14 – 3.10 (m, 2H), 2.78 – 2.74 (m, 2H), 2.10 – 2.03 (m, 2H), 1.53 (s, 2H), 1.44 (s, 9H).13C NMR (100 MHz, CD3OD) δ 145.0, 144.6, 143.9, 129.94, 128.7, 125.6, 124.5, 119.4, 117.0, 110.4, 27.4. HRMS (ESI, m / z): calculated for C25H32N5O2 [M+H]+: 434.25506; found 434.25595. Example 125: Synthesis of 1-(2-( amino)phenyl)piperidin-4-amine Prepared using general procedure 1.3 using tert-butyl (1-(2-((quinoxalin-6- ylmethyl)amino)phenyl)piperidin-4-yl)carbamate (31 mg, 0.07 mmol) and 2 M HCl in Et2O (0.4 Attorney Docket No.: 393976-00101 mL). The crude material was purified using RP MPLC (MeOH / 0.1% NH3 in H2O; 10-100%) then NP MPLC (0.1% NH4OH in MeOH / DCM; 0-10%) to yield 1-(2-((quinoxalin-6- ylmethyl)amino)phenyl)piperidin-4-amine (11 mg, 0.03 mmol, 45 % yield).1H NMR (400 MHz, CD3OD) δ 8.82 (s, 2H), 8.06 (d, J = 8.6 Hz, 1H), 8.04 – 8.00 (m, 1H), 7.87 (dd, J = 8.6, 1.9 Hz, 1H), 7.03 (dd, J = 7.8, 1.4 Hz, 1H), 6.84 (td, J = 7.7, 1.5 Hz, 1H), 6.61 (td, J = 7.6, 1.4 Hz, 1H), 6.52 (d, J = 7.9 Hz, 1H), 4.65 (s, 2H), 3.20 – 3.11 (m, 2H), 2.97 – 2.86 (m, 1H), 2.73 (td, J = 11.9, 2.4 Hz, 2H), 1.99 (br d, J = 12.1 Hz, 2H), 1.66 (qd, J = 11.7, 4.0 Hz, 2H).13C NMR (101 MHz, CD3OD) δ 145.0, 144.6, 143.9, 142.6, 142.5, 141.8, 139.4, 129.9, 128.7, 125.6, 124.6, 119.4, 117.0, 110.4, 50.6, 47.0, 34.2. Purity (LC): 99% Example 126: Synthesis of tert-butyl 4-yl)amino)azetidine-1-carboxylate Prepared using general procedure 1.1 using 3,4-dibromopyridine (800 mg, 3.4 mmol), tert- butyl 3-aminoazetidine-1-carboxylate (1.2 g, 7.1 mmol), and acetonitrile (4.2 mL). The crude material was purified using NP MPLC (EtOAc / Hex; 0-100%) to provide tert-butyl 3-((2- bromopyridin-4-yl)amino)azetidine-1-carboxylate as a white residue (43 mg, 0.1 mmol, 4% yield).1H NMR (400 MHz, CDCl3) (400 MHz, cdcl3) δ 7.90 (d, J = 5.8 Hz, 1H), 6.53 (d, J = 2.1 Hz, 1H), 6.36 (dd, J = 5.8, 2.2 Hz, 1H), 5.66 (d, J = 5.9 Hz, 1H), 4.29 (dd, J = 8.7, 7.3 Hz, 2H), 4.22 – 4.13 (m, 1H), 3.78 (dd, J = 9.3, 4.6 Hz, 2H), 1.42 (s, 9H).13C NMR (101 MHz, CDCl3) δ 156.1, 154.0, 149.5, 142.6, 110.4, 107.9, 80.2, 77.5, 56.4 (broad), 42.2, 28.4. HRMS (ESI, m / z): calculated for C13H19N3O2Br [M+H]+: 328.06548; found 328.06476. Example 127: Synthesis of 6-ylmethyl)amino)pyridin-4- yl)amino)azetidine-1-carboxylate Attorney Docket No.: 393976-00101 Prepared using general procedure 1.2 tert-butyl 3-((2-bromopyridin-4-yl)amino)azetidine- 1-carboxylate (65 mg, 0.2 mmol), quinoxalin-6-ylmethanamine (63 mg, 0.4 mmol), Pd2dba3 (7 mg, 0.008 mmol), BINAP (10 mg, 0.02 mmol), NaOtBu (38 mg, 0.4 mmol), and toluene (1.8 mL). The crude product was purified RP MPLC (MeCN / 0.1% NH3 in H2O; 10-100%) followed by RP MPLC (MeCN / 0.1% CHCO2H in H2O; 10-100%) to yield tert-butyl 3-((2-((quinoxalin-6- ylmethyl)amino)pyridin-4-yl)amino)azetidine-1-carboxylate as a yellow residue (6 mg, 0.03 mmol, 7% yield).1H NMR (400 MHz, CD3OD) δ 8.90 (br s, 2H), 8.15 (d, J = 8.7 Hz, 1H), 8.07 (d, J = 1.1 Hz, 7.88 (dd, J = 8.7, 1.9 Hz, 1H), 7.51 (d, J = 7.2 Hz, 1H), 6.24 (dd, J = 7.2, 2.2 Hz, 1H), 5.62 (s, 1H), 4.79 (s, 2H), 4.32 – 4.25 (m, 1H), 4.18 (app t, J = 8.0 Hz, 2H), 3.69 (dd, J = 9.1, 4.6 Hz, 2H).13C NMR (151 MHz, CD3OD) δ 169.0 (broad), 159.7 (broad), 159.2, 156.0 (broad), 148.3, 148.0, 145.2, 144.8, 142.7, 138.1 (broad), 132.12 128.8, 105.6 (broad), 87.9 (broad), 82.7, 57.9 (broad), 47.4, 44.4, 29.8. HRMS (ESI, m / z): calculated for C22H27N6O2 [M+H]+: 407.21898; found 407.21872. Example 128: Synthesis of (quinoxalin-6-ylmethyl)pyridine-2,4- diamine hydrochloride salt Prepared using general procedure 1.3 using tert-butyl 3-((2-((quinoxalin-6- ylmethyl)amino)pyridin-4-yl)amino)azetidine-1-carboxylate (5 mg, 0.01 mmol) in DCM (1 mL) and 2 M HCl in Et2O (0.1 mL, 0.2 mmol) to provide N4-(azetidin-3-yl)-N2-(quinoxalin-6- ylmethyl)pyridine-2,4-diamine hydrochloride as brown residue (5 mg, 0.01 mmol, 100% yield).1H NMR (400 MHz, CD3OD) δ 8.89 (app s, 2H), 8.14 (d, J = 8.7 Hz, 1H), 8.06 (d, J = 1.1 Hz, 1H), 7.89 (dd, J = 8.7, 2.0 Hz, 1H), 7.59 – 7.53 (m, 1H), 6.36 – 6.30 (m, 1H), 5.81 (br s, 1H), 4.71 – 4.63 (m, 1H), 4.42 – 4.32 (m, 2H), 4.09 – 3.98 (m, 2H).13C NMR (151 MHz, CD3OD) δ 146.4, 146.2, 143.0, 142.8, 142.2, 131.8, 130.3, 127.0, 53.9, 46.2, 45.3. The pyridine carbon resonances were not observed. HRMS (ESI, m / z): calculated for C17H19N6 [M+H]+: 307.16658; found 307.16589. Purity (LC): 98%. Attorney Docket No.: 393976-00101 References 1. Hajduk, P. J., Huth, J. R. & Tse, C. Predicting protein druggability. Drug Discov. Today 10, 1675–1682 (2005). 2. Vukovic, S. & Huggins, D. J. Quantitative metrics for drug–target ligandability. Drug Discov. Today 23, 1258–1266 (2018). 3. Batey, R. T., Rambo, R. P. & Doudna, J. A. Tertiary Motifs in RNA Structure and Folding. Angew. Chem. Int. Ed.38, 2326–2343 (1999). 4. Warner, K. D., Hajdin, C. E. & Weeks, K. M. Principles for targeting RNA with drug-like small molecules. Nat. Rev. Drug Discov.17, 547–558 (2018). 5. Sharp, P. A. The Centrality of RNA. Cell 136, 577–580 (2009). 6. Kozak, M. Regulation of translation via mRNA structure in prokaryotes and eukaryotes. Gene 361, 13–37 (2005). 7. Corbino, K. A., Sherlock, M. E., McCown, P. J., Breaker, R. R. & Stav, S. Riboswitch diversity and distribution. RNA 23, 995–1011 (2017). 8. Cech, T. R. & Steitz, J. A. The noncoding RNA revolution - Trashing old rules to forge new ones. Cell 157, 77–94 (2014). 9. Parsons, C., Slack, F. J., Zhang, W. C., Adams, B. D. & Walker, L. Targeting noncoding RNAs in disease. J. Clin. Invest.127, 761–771 (2017). 10. Matsui, M. & Corey, D. R. Non-coding RNAs as drug targets. Nat. Rev. Drug Discov.16, 167–179 (2017). 11. Guan, L. & Disney, M. D. Recent advances in developing small molecules targeting RNA. ACS Chem. Biol.7, 73–86 (2012). 12. Connelly, C. M., Moon, M. H. & Schneekloth, J. S. The Emerging Role of RNA as a Therapeutic Target for Small Molecules. Cell Chem. Biol.23, 1077–1090 (2016). 13. Murray, C. W. & Rees, D. C. The rise of fragment-based drug discovery. Nat. Chem. 1, 187–92 (2009). 14. Doak, B. C., Norton, R. S. & Scanlon, M. J. The ways and means of fragment-based drug design. Pharmacol. Ther.167, 28–37 (2016). 15. Cressina, E., Chen, L., Abell, C., Leeper, F. J. & Smith, A. G. Fragment screening against the thiamine pyrophosphate riboswitch thiM. Chem. Sci.2, 157–165 (2011). Attorney Docket No.: 393976-00101 16. Moumné, R., Catala, M., Larue, V., Micouin, L. & Tisné, C. Fragment-based design of small RNA binders: Promising developments and contribution of NMR. Biochimie 94, 1607–1619 (2012). 17. Warner, K. D. et al. Validating fragment-based drug discovery for biological RNAs: Lead fragments bind and remodel the TPP riboswitch specifically. Chem. Biol. 21, 591–595 (2014). 18. Zeiger, M. et al. Fragment based search for small molecule inhibitors of HIV-1 Tat-TAR. Bioorganic Med. Chem. Lett.24, 5576–5580 (2014). 19. Bottini, A. et al. Targeting Influenza A Virus RNA Promoter. Chem. Biol. Drug Des.86, 663–673 (2015). 20. Hunter, C. A. & Anderson, H. L. What is cooperativity? Angew. Chemie - Int. Ed. 48, 7488–7499 (2009). 21. Ichihara, O., Barker, J., Law, R. J. & Whittaker, M. Compound design by fragment-linking. Mol. Inform.30, 298–306 (2011). 22. Zeller, M. J., Li, K., Aubé, J. & Weeks, K. M. Multisite ligand recognition and cooperativity in the TPP riboswitch RNA. Prep. (2019). 23. Siegfried, N. A., Busan, S., Rice, G. M., Nelson, J. A. E. & Weeks, K. M. RNA motif discovery by SHAPE and mutational profiling (SHAPE-MaP). Nat. Methods 11, 959–65 (2014). 24. Smola, M. J., Rice, G. M., Busan, S., Siegfried, N. A. & Weeks, K. M. Selective 2’- hydroxyl acylation analyzed by primer extension and mutational profiling (SHAPE-MaP) for direct, versatile and accurate RNA structure analysis. Nat. Protoc. 10, 1643–1669 (2015). 25. Zeller, M. J.; Nuthanakanti, A.; Li, K.; Aubé, J.; Serganov, A.; Weeks, K. M., Subsite Ligand Recognition and Cooperativity in the TPP Riboswitch: Implications for Fragment- Linking in RNA Ligand Discovery. ACS Chem Biol 2022, 17 (2), 438-448. 26. Meanwell, N. A.; Loiseleur, O., Applications of Isosteres of Piperazine in the Design of Biologically Active Compounds: Part 1. Journal of Agricultural and Food Chemistry 2022, 70 (36), 10942-10971. 27. Umuhire Juru, A.; Hargrove, A. E., Frameworks for targeting RNA with small molecules. Journal of Biological Chemistry 2021, 296.

Claims

Attorney Docket No.: 393976-00101 That which is claimed:

1. A compound of Formula (I):wherein L1is selected ;R1 and R2 are selected from the group;and any pharmaceutically acceptable salt thereof.

2. The compound of claim 1, .110Attorney Docket No.: 393976-00101 3. The compound of claim 2, .

4. The compound of claim 2, .

5. The compound of claim 1, .

6. The compound of any one of claims 3-5, wherein R1and R2are selected from the group consisting .

7. The compound of claim 1, wherein the compound has the structure selected from the group consisting of 111Attorney Docket No.: 393976-00101 , , , ,8. The compound of claim 1, wherein the compound binds to a region of an RNA molecule. 112Attorney Docket No.: 393976-00101 9. The compound of claim 8, wherein the RNA molecule is a non-coding RNA molecule selected from rRNA, microRNAs, siRNAs, piRNAs, snoRNAs, snRNAs, exRNAs, and scaRNAs.

10. A composition comprising a therapeutically effective amount of the compound of claim 1 in a pharmaceutically acceptable carrier, diluent, or excipient.

11. A method of treating a disease or disorder associated with a dysfunction in RNA expression, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1.

12. The method of claim 11, wherein said disease or disorder is selected from genetic diseases, degenerative disorders, cancer, diabetes, autoimmune disorders, cardiovascular disorders, clotting disorders, diseases of the eye, infectious disease, and diseases caused by mutations in one or more gene. 113

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