Methods of preparing a PRMT5 inhibitor

Abstract

This disclosure relates to methods of making a PRMT5 inhibitor of Formula X.

Description

Attorney Docket No.: TGO-027WO METHODS OF PREPARING A PRMT5 INHIBITOR

[0001] The present application claims priority from U.S. Prov. Application Serial No.63 / 659,824, filed June 13, 2024, and U.S. Prov. Application Serial No.63 / 686,133 filed August 22, 2024, the disclosures of which are incorporated herein by reference in their entirety. BACKGROUND

[0002] Homozygous deletion of the CDKN2A region including methylthioadenosinephosphorylase (MTAP) is frequently observed in cancer, as it is an efficient mechanism for cancer cells to remove multiple tumor suppressor transcripts, including CDKN2A and CDKN2B. Protein arginine methyltransferase 5 (PRMT5) is a methyltransferase that utilizes the universal methyl donor S-adenosyl methionine (SAM) to add symmetric dimethylarginine (SDMA) posttranslational modifications to target proteins involved in a variety of essential cellular functions including RNA splicing, transcription, and translation. PRMT5 has been identified as a synthetic lethal target for cancers harboring homozygous deletion of the MTAP gene.

[0003] MTAP catalyzes the phosphorolysis of 5’-deoxy-5’-methylthioadenosine (MTA) toadenine and 5-methylthio-D-ribose-1-phosphate and is required for the methionine and adenosine salvage pathways. MTAP loss leads to the accumulation of MTA, which competes with SAM for binding to PRMT5, and is a moderately potent and selective inhibitor of PRMT5- dependent deposition of SDMA on key protein substrates. This renders cancer cells harboring MTAP deletions particularly vulnerable to further inhibition of PRMT5. Accordingly, there is a need in the art for safe and effective inhibitors of PRMT5.

[0004] The compound of the formula:,Attorney Docket No.: TGO-027WO is disclosed (together with a process for its preparation) in PCT publication WO2022 / 026892 as a PRMT5 inhibitor which may be useful, inter alia, for treating proliferating disorders (e.g., cancers) associated with MTAP deficiencies and / or MTA accumulation. A synthesis of N-(6- amino-5-ethylpyridin-3-yl)-2-((2R,5S)-5-methyl-2-(2-(1-methylpiperidin-4- yl)benzo[d]thiazol-5-yl)piperidin-1-yl)-2-oxoacetamide, is disclosed in WO 2022 / 026892, which is incorporated herein in its entirety by reference. While the synthetic procedures disclosed therein are suitable for preparing working quantities of the compounds described therein, alternative synthetic procedures which are more amenable to scale-up at high levels of purity are desirable. The present invention meets these and other needs. SUMMARY

[0005] Disclosed herein is a process for preparing the compound of Formula X:Formula X, which is also identified as N-(6-amino-5-ethylpyridin-3-yl)-2-((2R,5S)-5-methyl-2-(2-(1- methylpiperidin-4-yl)benzo[d]thiazol-5-yl)piperidin-1-yl)-2-oxoacetamide, and as TNG462.

[0006] Also disclosed herein are compounds of Formula B, Formula C, Formula D,Formula E, Formula F, Formula G, Formula H, Formula J, Formula K, Formula L,Formula M, Formula N, Formula O, Formula P and Formula R, and salts thereof, and saltsof Formula I, as described below. Further disclosed here in are processes for preparing compounds of Formula B, Formula C, Formula D, Formula E, Formula F, Formula G, Formula H, Formula J, Formula K, Formula L, Formula M, Formula N, Formula O,Formula P and Formula R, and salts thereof; and salts of Formula I, which are useful asintermediates for preparing the compound of Formula X. Applicants have found, surprisingly, that the processes described herein provide several advantages over prior methods, including (but not limited to) acceptable purity at scale.

[0007] In some embodiments, methods disclosed herein include a flow hydrogenation step.Attorney Docket No.: TGO-027WO

[0008] In some embodiments, methods disclosed herein result in a solid product, which has certain advantages over non-solid (e.g., oil) products. BRIEF DESCRIPTION OF THE DRAWINGS

[0009] FIG. 1 is an exemplary X-ray powder diffraction pattern of crystalline Form A of Compound A.

[0010] FIG. 2 is an exemplary X-ray powder diffraction pattern of crystalline Form B of Compound B.

[0011] FIG.3 is a scheme of the reactor used in Part 9, Step 2 of the Examples section.

[0012] FIG.4 is a scheme of the reactor used in Part 9, Step 3 of the Examples section.

[0013] FIG.5 is a scheme of the reactor used in Part 9, Step 4 of the Examples section. DEFINITIONS

[0014] As used in the present disclosure, the following words and phrases are generally intended to have the meanings as set forth below unless expressly indicated otherwise or the context in which they are used indicates otherwise.

[0015] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The abbreviations used herein have their conventional meaning within the chemical and biological arts. The chemical structures and formulae set forth herein are constructed according to the standard rules of chemical valency known in the chemical arts.

[0016] Throughout the description, where compositions and kits are described as having, including, or comprising specific components, or where processes and methods are described as having, including, or comprising specific steps, it is contemplated that, additionally, there are compositions and kits of the present invention that consist essentially of, or consist of, the recited components, and that there are processes and methods according to the present invention that consist essentially of, or consist of, the recited processing steps.

[0017] In the application, where an element or component is said to be included in and / or selected from a list of recited elements or components, it should be understood that the element or component can be any one of the recited elements or components, or the element or component can be selected from a group consisting of two or more of the recited elements or components.

[0018] Further, it should be understood that elements and / or features of a composition or a method described herein can be combined in a variety of ways without departing from the spiritAttorney Docket No.: TGO-027WO and scope of the present invention, whether explicit or implicit herein. For example, where reference is made to a particular compound, that compound can be used in various embodiments of compositions of the present invention and / or in methods of the present invention, unless otherwise understood from the context. Where elements are presented as lists, e.g., in Markush group format, each subgroup of the elements is also disclosed, and any element(s) can be removed from the group. In other words, within this application, embodiments have been described and depicted in a way that enables a clear and concise application to be written and drawn, but it is intended and will be appreciated that embodiments may be variously combined or separated without parting from the present teachings and invention(s). For example, it will be appreciated that all features described and depicted herein can be applicable to all aspects of the invention(s) described and depicted herein.

[0019] The articles “a” and “an” are used in this disclosure to refer to one or more than one (i.e., to at least one) of the grammatical object of the article, unless the context is inappropriate. By way of example, in certain contexts, “an element” means one element and / or in certain contexts more than one element. By way of another example, in certain contexts “a filler” means one filler and / or in certain contexts more than one filler (e.g., a mixture of two or more fillers).

[0020] The term “and / or” is used in this disclosure to mean either “and” or “or” unless indicated otherwise.

[0021] It should be understood that the expression “at least one of” includes individually each of the recited objects after the expression and the various combinations of two or more of the recited objects unless otherwise understood from the context and use. The expression “and / or” in connection with three or more recited objects should be understood to have the same meaning unless otherwise understood from the context.

[0022] Where the use of the term “about” is before a quantitative value, the present invention also includes the specific quantitative value itself, unless specifically stated otherwise. As used herein, the term “about” refers to a ±10% variation from the nominal value unless otherwise indicated or inferred from the context.

[0023] At various places in the present specification, variables or parameters are disclosed in groups or in ranges. It is specifically intended that the description include each and every individual subcombination of the members of such groups and ranges. For example, an integer in the range of 0 to 40 is specifically intended to individually disclose 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34,Attorney Docket No.: TGO-027WO 35, 36, 37, 38, 39, and 40, and an integer in the range of 1 to 20 is specifically intended to individually disclose 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, and 20. As a general matter, compositions specifying a percentage are by weight unless otherwise specified. Further, if a variable is not accompanied by a definition, then the previous definition of the variable controls.

[0024] The terms “disease,” “disorder,” and “condition” are used interchangeably herein.

[0025] The use of the term “include,” “includes,” “including,” “have,” “has,” “having,” “contain,” “contains,” or “containing,” including grammatical equivalents thereof, should be understood generally as open-ended and non-limiting, for example, not excluding additional unrecited elements or steps, unless otherwise specifically stated or understood from the context.

[0026] The use of any and all examples, or exemplary language herein, for example, “such as” or “including,” is intended merely to illustrate better the present invention and does not pose a limitation on the scope of the invention unless claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the present invention.

[0027] “Pharmaceutically acceptable” refers to compounds, molecular entities, compositions, materials and / or dosage forms that do not produce an adverse, allergic or other untoward reaction when administered to an animal, or human, as appropriate; or means approved or approvable by a regulatory agency of the federal or a state government or the corresponding agency in countries other than the United States, or that is listed in the U.S. Pharmacopoeia or other generally recognized pharmacopoeia for use in animals, and more particularly, in humans.

[0028] As is known to those of skill in the art, “salts” of compounds may be derived from inorganic or organic acids and bases. Examples of acids include, but are not limited to, hydrochloric, hydrobromic, sulfuric, nitric, perchloric, fumaric, maleic, phosphoric, glycolic, lactic, salicylic, succinic, toluene-p-sulfonic, tartaric, acetic, citric, methanesulfonic, ethanesulfonic, formic, benzoic, malonic, naphthalene-2-sulfonic and benzenesulfonic acid. Other acids, such as oxalic, while not in themselves pharmaceutically acceptable, may be employed in the preparation of salts useful as intermediates in obtaining the compounds described herein and their pharmaceutically acceptable acid addition salts.

[0029] Examples of bases include, but are not limited to, alkali metal (e.g., sodium and potassium) hydroxides, alkaline earth metal (e.g., magnesium and calcium) hydroxides, ammonia, and compounds of formula NW4+, wherein W is C1-4alkyl, and the like.Attorney Docket No.: TGO-027WO

[0030] Examples of salts include, but are not limited, to acetate, adipate, alginate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, citrate, camphorate, camphorsulfonate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, fumarate, flucoheptanoate, glycerophosphate, hemisulfate, heptanoate, hexanoate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonate, lactate, maleate, methanesulfonate, 2- naphthalenesulfonate, nicotinate, oxalate, palmoate, pectinate, persulfate, phenylpropionate, picrate, pivalate, propionate, succinate, tartrate, thiocyanate, tosylate, undecanoate, and the like. Other examples of salts include anions of the compounds of the present disclosure compounded with a suitable cation such as Na+, K+, Ca2+, NH4+, and NW4+(where W can be a C1-4alkyl group), and the like.

[0031] For therapeutic use, salts of the compounds of the present disclosure are contemplated as being pharmaceutically acceptable. However, salts of acids and bases that are non- pharmaceutically acceptable may also find use, for example, in the preparation or purification of a pharmaceutically acceptable compound.

[0032] As used herein, “pharmaceutical composition” or “pharmaceutical formulation” refer to the combination of a therapeutically active agent with a pharmaceutically acceptable excipient, inert or active, making the composition especially suitable for diagnostic or therapeutic use in vivo or ex vivo.

[0033] As used herein, “pharmaceutically acceptable excipient” refers to a substance that aids the administration of an active agent to and / or absorption by a subject and can be included in the compositions of the present disclosure without causing a significant adverse toxicological effect on the patient. Non-limiting examples of pharmaceutically acceptable excipients include binders, diluents, carriers, adjuvants, fillers (e.g., brittle diluents or fillers and ductile diluents or fillers), disintegrants, lubricants, coatings, sweeteners, flavors, gelatins, carbohydrates such as lactose, amylose or starch, fatty acid esters, hydroxypropylmethylcellulose, polyvinyl pyrrolidine, and colors, and the like. For examples of excipients, see Gennaro, Remington’s Pharmaceutical Sciences, 18thEd., Mack Publ. Co., Easton, PA (1990) or Shesky, Hancock, Moss and Goldfarb, Handbook of Pharmaceutical Excipients, 9thEd. Pharmaceutical Press, London, UK (2020).

[0034] A “subject” to which administration is contemplated includes, but is not limited to, humans (i.e., a male or female of any age group, e.g., a pediatric subject (e.g., infant, child, adolescent) or adult subject (e.g., young adult, middle–aged adult or senior adult)) and / or a non-human animal, e.g., a mammal such as primates (e.g., cynomolgus monkeys, rhesusAttorney Docket No.: TGO-027WO monkeys), cattle, pigs, horses, sheep, goats, rodents, cats, and / or dogs. In certain embodiments, the subject is a human. In certain embodiments, the subject is a non-human animal.

[0035] As used herein, and unless otherwise specified, the terms “treat,” “treating” and “treatment” contemplate an action that occurs while a subject is suffering from the specified disease, disorder or condition, which reduces the severity of the disease, disorder or condition, or retards or slows the progression of the disease, disorder or condition (“therapeutic treatment”), and also contemplates an action that occurs before a subject begins to suffer from the specified disease, disorder or condition (“prophylactic treatment”). In one embodiment, the compounds provided herein are contemplated to be used in methods of therapeutic treatment wherein the action occurs while a subject is suffering from the specified disease, disorder or condition and results in a reduction in the severity of the disease, disorder or condition, or retardation or slowing of the progression of the disease, disorder or condition. In an alternate embodiment, the compounds provided herein are contemplated to be used in methods of prophylactic treatment wherein the action occurs before a subject begins to suffer from the specified disease, disorder or condition and results in preventing a disease, disorder or condition, or one or more symptoms associated with the disease, disorder or condition, or preventing the recurrence of the disease, disorder or condition.

[0036] Definitions of specific functional groups and chemical terms are described in more detail below. The chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75th Ed., inside cover, and specific functional groups are generally defined as described therein. Additionally, general principles of organic chemistry, as well as specific functional moieties and reactivity, are described in Thomas Sorrell, Organic Chemistry, University Science Books, Sausalito, 1999; Smith and March, March’s Advanced Organic Chemistry, 5th Edition, John Wiley & Sons, Inc., New York, 2001; Larock, Comprehensive Organic Transformations, VCH Publishers, Inc., New York, 1989; and Carruthers, Some Modern Methods of Organic Synthesis, 3rd Edition, Cambridge University Press, Cambridge, 1987.

[0037] Compounds described herein can comprise one or more asymmetric centers, and thus can exist in various isomeric forms, e.g., enantiomers and / or diastereomers. For example, the compounds described herein can be in the form of an individual enantiomer, diastereomer or geometric isomer, or can be in the form of a mixture of stereoisomers, including racemic mixtures and mixtures enriched in one or more stereoisomer. Isomers can be isolated from mixtures by methods known to those skilled in the art, including chiral high-pressure liquidAttorney Docket No.: TGO-027WO chromatography (HPLC) and the formation and crystallization of chiral salts; or preferred isomers can be prepared by asymmetric syntheses. See, for example, Jacques et al., Enantiomers, Racemates and Resolutions (Wiley Interscience, New York, 1981); Wilen et al., Tetrahedron 33:2725 (1977); Eliel, Stereochemistry of Carbon Compounds (McGraw–Hill, NY, 1962); and Wilen, Tables of Resolving Agents and Optical Resolutions p.268 (E.L. Eliel, Ed., Univ. of Notre Dame Press, Notre Dame, IN 1972). Additionally encompassed are compounds described herein as individual isomers substantially free of other isomers, and alternatively, as mixtures of various isomers.

[0038] The “enantiomeric excess” (“e.e.” or “ee”) or “% enantiomeric excess” (“%e.e.” or “%ee”) of a composition as used herein refers to an excess of one enantiomer relative to the other enantiomer present in the composition. For example, a composition can contain 90% of one enantiomer, e.g., the S enantiomer, and 10% of the other enantiomer, i.e., the R enantiomer. e.e. = (90-10) / 100 = 80%.

[0039] Thus, a composition containing 90% of one enantiomer and 10% of the other enantiomer is said to have an enantiomeric excess of 80%.

[0040] The “diastereomeric excess” (“d.e.”) or “% diastereomeric excess” (“%d.e.”) of a composition as used herein refers to an excess of one diastereomer relative to one or more different diastereomers present in the composition. For example, a composition can contain 90% of one diastereomer, and 10% of one or more different diastereomers. d.e. = (90-10) / 100 = 80%.

[0041] Thus, a composition containing 90% of one diastereomers and 10% of one or more different diastereomers is said to have a diastereomeric excess of 80%.

[0042] As used herein, the term “tautomers” refers to isomers of a compound that differ from each other in the position of a proton or in electronic distribution. Compounds described herein also include all tautomers (e.g., proton migration tautomers and valence tautomers). It is understood that more than two tautomers may exist for a given compound. In some embodiments, tautomers exist in equilibrium and are readily converted from one isomeric form to another. In some embodiments, this conversion results in the formal migration of a hydrogen atom accompanied by a switch of adjacent conjugated double bonds. In some embodiments, tautomers exist as a mixture of a tautomeric set in solution. In solutions where tautomerization is possible, a chemical equilibrium of the tautomers will be reached. The exact ratio of the tautomers depends on several factors, including temperature, solvent and pH. The concept of tautomers that are interconvertible by tautomerizations is called tautomerism. An example of aAttorney Docket No.: TGO-027WO moiety existing in several tautomeric forms is 1,2,4-triazole, which exists in tautomeric forms known as 1H-1,2,4-triazole, 4H-1,2,4-triazole and 3H-1,2,4-triazole which interconvert rapidly.

[0043] Common tautomeric forms include, but are not limited to, ketone-enol, amide-nitrile,lactam-lactim, amide-imidic acid tautomerism in heterocyclic rings (e.g., in nucleobases such as guanine, thymine and cytosine), imine-enamine, and enamine-enamine. Compounds described herein which exist in multiple tautomeric forms include all such forms encompassed by a given tautomeric formula.

[0044] When a range of values is listed, it is intended to encompass each value and sub–rangewithin the range. For example, “C1–6alkyl” or “C1-C6alkyl” is intended to encompass, C1, C2, C3, C4, C5, C6, C1–6, C1–5, C1–4, C1–3, C1–2, C2–6, C2–5, C2–4, C2–3, C3–6, C3–5, C3–4, C4–6, C4–5, and C5–6 alkyl. It should also be understood that when described herein any of the moieties defined forth below may be substituted with a variety of substituents, and that the respective definitions are intended to include such substituted moieties within their scope as set out below. Unless otherwise stated, the term “substituted” is to be defined as set out below. It should be further understood that the terms “groups” and “radicals” can be considered interchangeable when used herein. The articles “a” and “an” may be used herein to refer to one or to more than one (i.e. at least one) of the grammatical objects of the article. By way of example “an analogue” means one analogue or more than one analogue.

[0045] “Alkyl” refers to a radical of a straight–chain or branched saturated hydrocarbon grouphaving from 1 to 20 carbon atoms (“C1–20alkyl” or “C1-C20alkyl”). In some embodiments, an alkyl group has 1 to 12 carbon atoms (“C1–12alkyl”). In some embodiments, an alkyl group has 1 to 10 carbon atoms (“C1–10alkyl”). In some embodiments, an alkyl group has 1 to 9 carbon atoms (“C1–9alkyl”). In some embodiments, an alkyl group has 1 to 8 carbon atoms (“C1–8alkyl”). In some embodiments, an alkyl group has 1 to 7 carbon atoms (“C1–7alkyl”). In some embodiments, an alkyl group has 1 to 6 carbon atoms (“C1–6alkyl”, also referred to herein as “lower alkyl”). In some embodiments, an alkyl group has 1 to 5 carbon atoms (“C1–5alkyl”). In some embodiments, an alkyl group has 1 to 4 carbon atoms (“C1–4alkyl”). In some embodiments, an alkyl group has 1 to 3 carbon atoms (“C1–3alkyl”). In some embodiments, an alkyl group has 1 to 2 carbon atoms (“C1–2alkyl”). In some embodiments, an alkyl group has 1 carbon atom (“C1alkyl”). In some embodiments, an alkyl group has 2 to 6 carbon atomsAttorney Docket No.: TGO-027WO (“C2–6 alkyl”). Examples of C1–6 alkyl groups include methyl (C1), ethyl (C2), n–propyl (C3), isopropyl (C3), n–butyl (C4), tert–butyl (C4), sec–butyl (C4), iso–butyl (C4), n–pentyl (C5), 3– pentanyl (C5), amyl (C5), neopentyl (C5), 3–methyl–2–butanyl (C5), tertiary amyl (C5), and n– hexyl (C6). Additional examples of alkyl groups include n–heptyl (C7), n–octyl (C8) and the like. Unless otherwise specified, each instance of an alkyl group is independently optionally substituted, i.e., unsubstituted (an “unsubstituted alkyl”) or substituted (a “substituted alkyl”) with one or more substituents; e.g., for instance from 1 to 5 substituents, 1 to 3 substituents, or 1 substituent. In certain embodiments, the alkyl group is unsubstituted C1–10alkyl (e.g., –CH3). In certain embodiments, the alkyl group is substituted C1–10alkyl. Common alkyl abbreviations include –Me (–CH3), –Et (–CH2CH3), –iPr (–CH(CH3)2), –nPr (–CH2CH2CH3), –nBu (–CH2C CH2CH2CH3), –iBu (–CH2CH(CH3)2), or –tBu (–C(CH3)3).

[0046] “Amino” refers to the radical –NH2.

[0047] A “nitrogen protecting group” or an “amino protecting group” is a substituent present on the nitrogen of an amino group. Exemplary nitrogen protecting groups include, but are not limited to, −OH, −ORaa, −N(Rcc)2, −C(=O)Raa, −C(=O)N(Rcc)2, −CO2Raa, −SO2Raa, −C(=NRcc)Raa, −C(=NRcc)ORaa, −C(=NRcc)N(Rcc)2, −SO2N(Rcc)2, −SO2Rcc, −SO2ORcc, −SORaa, −C(=S)N(Rcc)2, −C(=O)SRcc, −C(=S)SRcc, −C1-10alkyl (e.g., aralkyl, heteroaralkyl), −C2-10alkenyl, −C2-10alkynyl, heteroC1-10alkyl, heteroC2-10alkenyl, heteroC2-10alkynyl, C3-10carbocyclyl, 3-14 membered heterocyclyl, C6-14aryl, and 5-14 membered heteroaryl groups, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aralkyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 Rddgroups, and wherein Raa, Rbb, Rccand Rddare as defined herein. Nitrogen protecting groups are well known in the art and include those described in detail in Protecting Groups in Organic Synthesis, T. W. Greene and P. G. M. Wuts, 3rd edition, John Wiley & Sons, 1999, incorporated herein by reference.

[0048] Each instance of Raais, independently, selected from −C1-10alkyl, −C1-10perhaloalkyl, −C2-10alkenyl, −C2-10alkynyl, heteroC1-10alkyl, heteroC2-10alkenyl, heteroC2-10alkynyl, C3-10carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl, or two Raagroups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 Rddgroups;

[0049] each instance of Raais, independently, selected from hydrogen, −OH, −ORaa, −N(Rcc)2,Attorney Docket No.: TGO-027WO−SO2N(Rcc)2,−SO2Rcc,−SO2ORcc,−SORaa,−C(=S)N(Rcc)2,−C(=O)SRcc,−C(=S)SRcc,−P(=O)(Raa)2, −P(=O)(ORcc)2, −P(=O)(N(Rcc)2)2, −C1-10alkyl, −C1-10perhaloalkyl, −C2-10alkenyl, −C2-10alkynyl, heteroC1-10alkyl, heteroC2-10alkenyl, heteroC2-10alkynyl, C3-10carbocyclyl, 3-14 membered heterocyclyl, C6-14aryl, and 5-14 membered heteroaryl, or two Raagroups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 Rddgroups; wherein X− is a counterion;

[0050] each instance of Rccis, independently, selected from hydrogen, −C1-10alkyl, −C1-10perhaloalkyl, −C2-10alkenyl, −C2-10alkynyl, heteroC1-10alkyl, heteroC2-10alkenyl, heteroC2-10alkynyl, C3-10carbocyclyl, 3-14 membered heterocyclyl, C6-14aryl, and 5-14 membered heteroaryl, or two Rccgroups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 Rddgroups;

[0051] each instance of Rddis, independently, selected from halogen, −CN, −NO2, −N3,6alkynyl, C3-10carbocyclyl, 3-10 membered heterocyclyl, C6-10aryl, 5-10 membered heteroaryl, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 Rgggroups, or two geminal Rddsubstituents can be joined to form =O or =S; wherein X− is a counterion;

[0052] each instance of Reeis, independently, selected from −C1-6alkyl, −C1-6perhaloalkyl, −C2-6alkenyl, −C2-6alkynyl, heteroC1-6alkyl, heteroC2-6alkenyl, heteroC2-6alkynyl, C3-10carbocyclyl, C6-10aryl, 3-10 membered heterocyclyl, and 3-10 membered heteroaryl, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 Rgggroups;Attorney Docket No.: TGO-027WO

[0053] each instance of Rffis, independently, selected from hydrogen,−C1-6 alkyl,perhaloalkyl, −C2-6alkenyl, −C2-6alkynyl, heteroC1-6alkyl, heteroC2-6alkenyl, heteroC2-6alkynyl, C3-10carbocyclyl, 3-10 membered heterocyclyl, C6-10aryl and 5-10 membered heteroaryl, or two Rffgroups are joined to form a 3-10 membered heterocyclyl or 5-10 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 Rgggroups; and

[0054] each instance of Rggis, independently, halogen, −CN, −NO2, −N3, −SO2H, −SO3H, −OH, −OC1-6alkyl, −ON(C1-6alkyl)2, −N(C1-6alkyl)2, −N(C1-6alkyl)3+X−, −NH(C1-6alkyl)2+X−, −NH2(C1-6alkyl)+X−, −NH3+X−, −N(OC1-6alkyl)(C1-6alkyl), −N(OH)(C1-6alkyl), −NH(OH), −SH, −SC1-6alkyl, −SS(C1-6alkyl), −C(=O)(C1-6alkyl), −CO2H, −CO2(C1-6alkyl),−OC(=O)(C1-6 alkyl),−OCO2(C1-6 alkyl),−C(=O)NH2,−C(=O)N(C1-6 alkyl)2,−OC(=O)NH(C1-6 alkyl),−NHC(=O)(C1-6 alkyl),−N(C1-6 alkyl)C(=O)(C1-6 alkyl),−NHCO2(C1-6alkyl), −NHC(=O)N(C1-6 alkyl)2, −NHC(=O)NH(C1-6 alkyl), −NHC(=O)NH2, −C(=NH)O(C1-6 alkyl), −OC(=NH)(C1-6alkyl), −OC(=NH)OC1-6alkyl, −C(=NH)N(C1-6alkyl)2, −C(=NH)NH(C1-6alkyl), −C(=NH)NH2, −OC(=NH)N(C1-6alkyl)2, −OC(NH)NH(C1-6alkyl), −OC(NH)NH2, −NHC(NH)N(C1-6alkyl)2, −NHC(=NH)NH2, −NHSO2(C1-6alkyl), −SO2N(C1-6alkyl)2, −SO2NH(C1-6alkyl), −SO2NH2, −SO2C1-6alkyl, −SO2OC1-6alkyl, −OSO2C1-6alkyl, −SOC1-6alkyl, −Si(C1-6alkyl)3, −OSi(C1-6alkyl)3 −C(=S)N(C1-6alkyl)2, −C(=S)NH(C1-6alkyl), −C(=S)NH2, −C(=O)S(C1-6alkyl), −C(=S)SC1-6alkyl, −SC(=S)SC1-6alkyl, −P(=O)(OC1-6alkyl)2, −P(=O)(C1-6alkyl)2, −OP(=O)(C1-6alkyl)2, −OP(=O)(OC1-6alkyl)2, −C1-6alkyl, −C1-6perhaloalkyl, −C2-6alkenyl, −C2-6alkynyl, heteroC1-6alkyl, heteroC2-6alkenyl, heteroC2-6alkynyl, C3-10carbocyclyl, C6-10 aryl, 3-10 membered heterocyclyl, 5-10 membered heteroaryl; or two geminal Rggsubstituents can be joined to form =O or =S; wherein X− is a counterion.

[0055] For example, nitrogen protecting groups such as amide groups (e.g., −C(=O)Raa) include, but are not limited to, formamide, acetamide, chloroacetamide, trichloroacetamide, trifluoroacetamide, phenylacetamide, 3-phenylpropanamide, picolinamide, 3- pyridylcarboxamide, N-benzoylphenylalanyl derivative, benzamide, p-phenylbenzamide, o- nitrophenylacetamide, o-nitrophenoxyacetamide, acetoacetamide, (N’- dithiobenzyloxyacylamino)acetamide, 3-(p-hydroxyphenyl)propanamide, 3-(o- nitrophenyl)propanamide, 2-methyl-2-(o-nitrophenoxy)propanamide, 2-methyl-2-(o- phenylazophenoxy)propanamide, 4-chlorobutanamide, 3-methyl-3-nitrobutanamide, o-Attorney Docket No.: TGO-027WO nitrocinnamide, N-acetylmethionine derivative, o-nitrobenzamide and o- (benzoyloxymethyl)benzamide.

[0056] Nitrogen protecting groups such as carbamate groups (e.g., −C(=O)ORaa) include, butare not limited to, methyl carbamate, ethyl carbamate, 9-fluorenylmethyl carbamate (Fmoc), 9-(2-sulfo)fluorenylmethyl carbamate, 9-(2,7-dibromo)fluorenylmethyl carbamate, 2,7-di-t- butyl-[9-(10,10-dioxo-10,10,10,10-tetrahydrothioxanthyl)]methyl carbamate (DBD-Tmoc), 4- methoxyphenacyl carbamate (Phenoc), 2,2,2-trichloroethyl carbamate (Troc), 2- trimethylsilylethyl carbamate (Teoc), 2-phenylethyl carbamate (hZ), 1-(1-adamantyl)-1- methylethyl carbamate (Adpoc), 1,1-dimethyl-2-haloethyl carbamate, 1,1-dimethyl-2,2- dibromoethyl carbamate (DB-t-BOC), 1,1-dimethyl-2,2,2-trichloroethyl carbamate (TCBOC), 1-methyl-1-(4-biphenylyl)ethyl carbamate (Bpoc), 1-(3,5-di-t-butylphenyl)-1-methylethyl carbamate (t-Bumeoc), 2-(2’– and 4’-pyridyl)ethyl carbamate (Pyoc), 2-(N,N- dicyclohexylcarboxamido)ethyl carbamate, t-butyl carbamate (BOC or Boc, which has the structure), 1-adamantyl carbamate (Adoc), vinyl carbamate (Voc), allyl carbamate (Alloc), 1-isopropylallyl carbamate (Ipaoc), cinnamyl carbamate (Coc), 4- nitrocinnamyl carbamate (Noc), 8-quinolyl carbamate, N-hydroxypiperidinyl carbamate, alkyldithio carbamate, benzyl carbamate (Cbz), p-methoxybenzyl carbamate (Moz), p- nitobenzyl carbamate, p-bromobenzyl carbamate, p-chlorobenzyl carbamate, 2,4- dichlorobenzyl carbamate, 4-methylsulfinylbenzyl carbamate (Msz), 9-anthrylmethyl carbamate, diphenylmethyl carbamate, 2-methylthioethyl carbamate, 2-methylsulfonylethyl carbamate, 2-(p-toluenesulfonyl)ethyl carbamate, [2-(1,3-dithianyl)]methyl carbamate (Dmoc), 4-methylthiophenyl carbamate (Mtpc), 2,4-dimethylthiophenyl carbamate (Bmpc), 2- phosphonioethyl carbamate (Peoc), 2-triphenylphosphonioisopropyl carbamate (Ppoc), 1,1- dimethyl-2-cyanoethyl carbamate, m-chloro-p-acyloxybenzyl carbamate, p- (dihydroxyboryl)benzyl carbamate, 5-benzisoxazolylmethyl carbamate, 2-(trifluoromethyl)-6- chromonylmethyl carbamate (Tcroc), m-nitrophenyl carbamate, 3,5-dimethoxybenzyl carbamate, o-nitrobenzyl carbamate, 3,4-dimethoxy-6-nitrobenzyl carbamate, phenyl (o- nitrophenyl)methyl carbamate, t-amyl carbamate, S-benzyl thiocarbamate, p-cyanobenzyl carbamate, cyclobutyl carbamate, cyclohexyl carbamate, cyclopentyl carbamate, cyclopropylmethyl carbamate, p-decyloxybenzyl carbamate, 2,2-dimethoxyacylvinyl carbamate, o-(N,N-dimethylcarboxamido)benzyl carbamate, 1,1-dimethyl-3-(N,N- dimethylcarboxamido)propyl carbamate, 1,1-dimethylpropynyl carbamate, di(2-Attorney Docket No.: TGO-027WO pyridyl)methyl carbamate, 2-furanylmethyl carbamate, 2-iodoethyl carbamate, isobornyl carbamate, isobutyl carbamate, isonicotinyl carbamate, p-(p’-methoxyphenylazo)benzyl carbamate, 1-methylcyclobutyl carbamate, 1-methylcyclohexyl carbamate, 1-methyl-1- cyclopropylmethyl carbamate, 1-methyl-1-(3,5-dimethoxyphenyl)ethyl carbamate, 1-methyl- 1-(p-phenylazophenyl)ethyl carbamate, 1-methyl-1-phenylethyl carbamate, 1-methyl-1-(4- pyridyl)ethyl carbamate, phenyl carbamate, p-(phenylazo)benzyl carbamate, 2,4,6-tri-t- butylphenyl carbamate, 4-(trimethylammonium)benzyl carbamate, and 2,4,6-trimethylbenzyl carbamate.

[0057] Nitrogen protecting groups such as sulfonamide groups (e.g., −S(=O)2Raa) include, but are not limited to, p-toluenesulfonamide (Ts), benzenesulfonamide, 2,3,6-trimethyl-4- methoxybenzenesulfonamide (Mtr), 2,4,6-trimethoxybenzenesulfonamide (Mtb), 2,6- dimethyl-4-methoxybenzenesulfonamide (Pme), 2,3,5,6-tetramethyl-4- methoxybenzenesulfonamide (Mte), 4-methoxybenzenesulfonamide (Mbs), 2,4,6- trimethylbenzenesulfonamide (Mts), 2,6-dimethoxy-4-methylbenzenesulfonamide (iMds), 2,2,5,7,8-pentamethylchroman-6-sulfonamide (Pmc), methanesulfonamide (Ms), β- trimethylsilylethanesulfonamide (SES), 9-anthracenesulfonamide, 4-(4’,8’- dimethoxynaphthylmethyl)benzenesulfonamide (DNMBS), benzylsulfonamide, trifluoromethylsulfonamide, and phenacylsulfonamide.

[0058] Other nitrogen protecting groups include, but are not limited to, phenothiazinyl-(10)- acyl derivative, N’-p-toluenesulfonylaminoacyl derivative, N’-phenylaminothioacyl derivative, N-benzoylphenylalanyl derivative, N-acetylmethionine derivative, 4,5-diphenyl-3-oxazolin-2- one, N-phthalimide, N-dithiasuccinimide (Dts), N-2,3-diphenylmaleimide, N-2,5- dimethylpyrrole, N-1,1,4,4-tetramethyldisilylazacyclopentane adduct (STABASE), 5- substituted 1,3-dimethyl-1,3,5-triazacyclohexan-2-one, 5-substituted 1,3-dibenzyl-1,3,5- triazacyclohexan-2-one, 1-substituted 3,5-dinitro-4-pyridone, N-methylamine, N-allylamine, N-[2-(trimethylsilyl)ethoxy]methylamine (SEM), N-3-acetoxypropylamine, N-(1-isopropyl-4- nitro-2-oxo-3-pyroolin-3-yl)amine, quaternary ammonium salts, N-benzylamine, N-di(4- methoxyphenyl)methylamine, N-5-dibenzosuberylamine, N-triphenylmethylamine (Tr), N- [(4-methoxyphenyl)diphenylmethyl]amine (MMTr), N-9-phenylfluorenylamine (PhF), N-2,7- dichloro-9-fluorenylmethyleneamine, N-ferrocenylmethylamino (Fcm), N-2-picolylamino N’- oxide, N-1,1-dimethylthiomethyleneamine, N-benzylideneamine, N-p- methoxybenzylideneamine, N-diphenylmethyleneamine, N-[(2- pyridyl)mesityl]methyleneamine, N-(N’,N’-dimethylaminomethylene)amine, N,N’-Attorney Docket No.: TGO-027WO isopropylidenediamine, N-p-nitrobenzylideneamine, N-salicylideneamine, N-5- chlorosalicylideneamine, N-(5-chloro-2-hydroxyphenyl)phenylmethyleneamine, N- cyclohexylideneamine, N-(5,5-dimethyl-3-oxo-1-cyclohexenyl)amine, N-borane derivative, N-diphenylborinic acid derivative, N-[phenyl(pentaacylchromium– or tungsten)acyl]amine, N-copper chelate, N-zinc chelate, N-nitroamine, N-nitrosoamine, amine N-oxide, diphenylphosphinamide (Dpp), dimethylthiophosphinamide (Mpt), diphenylthiophosphinamide (Ppt), dialkyl phosphoramidates, dibenzyl phosphoramidate, diphenyl phosphoramidate, benzenesulfenamide, o-nitrobenzenesulfenamide (Nps), 2,4- dinitrobenzenesulfenamide, pentachlorobenzenesulfenamide, 2-nitro-4- methoxybenzenesulfenamide, triphenylmethylsulfenamide, and 3-nitropyridinesulfenamide (Npys).

[0059] “Carboxy” refers to the radical –C(=O)OH.

[0060] “Halo” or “halogen” refers to fluoro (F), chloro (Cl), bromo (Br), and iodo (I).

[0061] “Hydroxy” refers to the radical –OH.

[0062] “Nitro” refers to the radical –NO2.

[0063] A “counterion” or “anionic counterion” is a negatively charged group associated with a cationic quaternary amino group in order to maintain electronic neutrality. Exemplary counterions include halide ions (e.g., F–, Cl–, Br–, I–), NO3–, ClO4–, OH–, H2PO4–, HSO4–, SO4-2sulfonate ions (e.g., methansulfonate, trifluoromethanesulfonate, p–toluenesulfonate, benzenesulfonate, 10–camphor sulfonate, naphthalene–2–sulfonate, naphthalene–1–sulfonic acid–5–sulfonate, ethan–1–sulfonic acid–2–sulfonate, and the like), and carboxylate ions (e.g., acetate, ethanoate, propanoate, benzoate, glycerate, lactate, tartrate, glycolate, and the like).

[0064] Nitrogen atoms can be substituted or unsubstituted as valency permits, and include primary, secondary, tertiary, and quarternary nitrogen atoms. Exemplary nitrogen atom substitutents include, but are not limited to, hydrogen, –OH, –ORaa, –N(Rcc)2, –CN, –C(=O)Raa, –C(=O)N(Rcc)2, –CO2Raa, –SO2Raa, –C(=NRaa)Raa, –C(=NRcc)ORaa, –C(=NRcc)N(Rcc)2, – SO2N(Rcc)2, –SO2Rcc, –SO2ORcc, –SORaa, –C(=S)N(Rcc)2, –C(=O)SRcc, –C(=S)SRcc, – P(=O)2Raa, –P(=O)(Raa)2, –P(=O)2N(Rcc)2, –P(=O)(NRcc)2, C1–10 alkyl, C1–10 haloalkyl, C2– 10 alkenyl, C2–10 alkynyl, C3–10 carbocyclyl, 3–14 membered heterocyclyl, C6–14 aryl, and 5–14 membered heteroaryl, or two Rccgroups attached to a nitrogen atom are joined to form a 3–14 membered heterocyclyl or 5–14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 Rddgroups, and wherein Raa, Raa, Rccand Rddare as defined above.Attorney Docket No.: TGO-027WO

[0065] These and other exemplary substituents are described in more detail in the DetailedDescription, Examples, and Claims. The invention is not intended to be limited in any manner by the above exemplary listing of substituents. DETAILED DESCRIPTION

[0066] In some embodiments, there is provided an improved process for the preparation of N-(6-amino-5-ethylpyridin-3-yl)-2-((2R,5S)-5-methyl-2-(2-(1-methylpiperidin-4- yl)benzo[d]thiazol-5-yl)piperidin-1-yl)-2-oxoacetamide, having Formula X:also identified as TNG462.

[0067] In some embodiments, provided herein are compounds of Formula B, Formula C,Formula D, Formula E, Formula F, Formula G, Formula H, Formula J, Formula K,Formula L, Formula M, Formula N, Formula O, Formula P and Formula R, and saltsthereof, and salts of Formula I, and processes for their preparation, which are useful asbuilding blocks / intermediates in the synthesis of the compound of Formula X. Compounds – Intermediates

[0068] Disclosed herein is a compound of Formula A1:Formula A1, or a salt thereof, wherein R1is a chiral auxiliary.

[0069] In any of the embodiments herein, R1 is an optionally substituted oxazolidinone. In anyof the embodiments herein,, wherein R10is C1-C6alkyl, benzyl (Bn), or phenyl (Ph).Attorney Docket No.: TGO-027WO

[0070] In any of the embodiments herein, R10 is C1-C6 alkyl. In any of the embodiments herein,R10is benzyl (Bn). In any of the embodiments herein, R10is phenyl (Ph).

[0071] In any of the embodiments herein,any of the embodiments herein,the compound of Formula A1 has the structure INT-0:, or a salt thereof.

[0072] In some embodiments, provided herein is a compound of Formula A2:or a salt thereof, wherein R11is C1-C6alkyl.

[0073] In any of the embodiments herein, R11 is –Me, –Et, –nPr, –iPr, –nBu, or –tBu. In anyof the embodiments herein, R11is –Me. In any of the embodiments herein, R11is –Et. In any of the embodiments herein, R11is –nPr. In any of the embodiments herein, R11is –iPr. In any of the embodiments herein, R11is –nBu. In any of the embodiments herein, R11is –tBu.

[0074] In any of the embodiments herein, the compound of Formula A2 is INT-1:, or a salt thereof.

[0075] Disclosed herein is a compound of Formula B:Formula B, or a salt thereof.

[0076] In some embodiments described herein, the compound of Formula B is alternativelyidentified as INT-2.Attorney Docket No.: TGO-027WO

[0077] Disclosed herein is a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group.

[0078] In any of the embodiments herein, the compound of Formula C is INT-3:INT-3, or a salt thereof.

[0079] Disclosed herein is a compound of Formula C-1:Formula C-1, or a salt thereof, wherein R2is a nitrogen protecting group, and R4is alkyl sulfonate, haloalkyl sulfonate, or aryl sulfonate.

[0080] In any of the embodiments herein, R2 is a carbamate. In any of the embodiments herein,.

[0081] In any of the embodiments herein, R4 is alkyl sulfonate. In any of the embodimentsherein, R4is haloalkyl sulfonate. In any of the embodiments herein, R4is aryl sulfonate (e.g., methanesulfonate (–OS(=O)2CH3, trifluoromethanesulfonate (–OS(=O)2CF3), phenyl sulfonate (–OS(=O)2Ph), toluenesulfonate (–OS(=O)2C6H4-CH3)). In any of the embodiments herein, R4is trifluoromethanesulfonate (–OS(=O)2CF3).

[0082] In any of the embodiments herein, the compound of Formula C-1 is INT-8:INT-8,Attorney Docket No.: TGO-027WO or a salt thereof.

[0083] In some embodiments, provided herein is a compound of Formula D:Formula D, or a salt thereof, wherein R3is a boronic acid or a boronic ester.

[0084] In any of the embodiments herein, R3 is a boronic ester.

[0085] In any of the embodiments herein, R3 is,wherein each of R3aand R3bis, independently, H or C1-6 alkyl, or wherein R3aand R3bare joined together with their intervening atoms to form a 5-10 membered ring that is optionally substituted with 0, 1, 2, 3, 4, 5, or 6 instances of R3c, wherein each R3cis, independently, C1-6alkyl.

[0086] In any of the embodiments herein, each of R3a and R3b is, independently, C1-6 alkyl. Inany of the embodiments herein, R3aand R3bare joined together with their intervening atoms to form a 5-10 membered ring that is optionally substituted with 0, 1, 2, 3, 4, 5, or 6 instances of R3c, wherein each R3cis, independently, C1-6alkyl. In any of the embodiments herein, R3aand R3bare joined together with their intervening atoms to form a 5-6 membered ring that is optionally substituted with 0, 1, 2, 3, 4, 5, or 6 instances of R3c, wherein each R3cis –Me. In any of the embodiments herein, R3is.

[0087] In any of the embodiments herein, the compound of Formula D is INT-7:or a salt thereof.

[0088] In some embodiments, provided herein is a compound of Formula E:Attorney Docket No.: TGO-027WOor a salt thereof, wherein R2is a nitrogen protecting group.

[0089] In any of the embodiments herein, the compound depicted by Formula E is INT-9:INT-9, or a salt thereof.

[0090] In some embodiments, provided herein is a compound of Formula F:or a salt thereof.

[0091] In some embodiments, provided herein is a compound of Formula F:or a salt thereof.Attorney Docket No.: TGO-027WO

[0092] It is understood that the compound of Formula F is capable of imine-enaminetautomerism. Thus, one of ordinary skill in the art will readily appreciate that the compound of Formula F may be depicted as the imine form:or as the enamine form:and that a sample may comprise the imine form or the enamine form, or mixtures thereof, with the relative proportions of each depending on the conditions present. In some embodiments, the imine form is the predominant form. In some embodiments, the ratio of the imine:enamine forms is about 10:1.

[0093] In any of the embodiments herein, the compound of Formula F may be alternativelyidentified as INT-10 and tautomers thereof.

[0094] In some embodiments, provided herein is a compound of Formula G:Formula G,or a salt thereof.

[0095] In any of the embodiments herein, the compound of Formula G may be alternativelyidentified as INT-11.Attorney Docket No.: TGO-027WO

[0096] In some embodiments, the weights are based upon total weight of all isomers of thecompound depicted by Formula G. In some embodiments, the weights are based upon total weight of four diastereomers of the compound depicted by Formula G.

[0097] Disclosed herein is a compound of Formula H, or a salt thereof:Formula H, wherein each of R6and R7is an independently selected nitrogen protecting group.

[0098] In any of the embodiments herein, R6 is a carbamate. In any of the embodiments herein,

[0099] In any of the embodiments herein, R7 is a carbamate. In any of the embodiments herein,

[0100] In any of the embodiments herein, the compound of Formula H is INT-17:INT-17, or a salt thereof.

[0101] In some embodiments, there is provided a salt of the compound of Formula I:Formula I, wherein each of R8and R9is, independently, H or a nitrogen protecting group.Attorney Docket No.: TGO-027WO

[0102] In any of the embodiments herein, the salt of the compound of Formula I is apharmaceutically acceptable salt. In any of the embodiments herein, the salt of the compound of Formula I is selected from a formic acid salt of the compound of Formula I, a phosphoric acid salt of the compound of Formula I, the sulfuric acid salt of the compound of Formula I, and the benzoic acid salt of the compound of Formula I.

[0103] In any of the embodiments herein, the salt of the compound of Formula I is a crystallineform of the salt of the compound of Formula I.

[0104] Disclosed herein is a compound of Formula J:Formula J, or a salt thereof.

[0105] In some embodiments described herein, the compound of Formula J is alternativelyidentified as INT-18.

[0106] Disclosed herein is a compound of Formula K:or a salt thereof.

[0107] In some embodiments described herein, the compound of Formula K is alternativelyidentified as INT-19.

[0108] Disclosed herein is a compound of Formula L:Formula L, or a salt thereof.

[0109] In some embodiments described herein, the compound of Formula L is alternativelyidentified as INT-20.

[0110] Disclosed herein is a compound of Formula M:Formula M, or a salt thereof.Attorney Docket No.: TGO-027WO

[0111] In some embodiments described herein, the compound of Formula M is alternativelyidentified as INT-21.

[0112] Disclosed herein is a compound of Formula N:Formula N, or a salt thereof.

[0113] In some embodiments described herein, the compound of Formula N is alternativelyidentified as INT-22.

[0114] Disclosed herein is a compound of Formula O, or a salt thereof:Formula O, wherein each of R6and R7is an independently selected nitrogen protecting group.

[0115] In any of the embodiments herein, R6 is a carbamate. In any of the embodiments herein,.

[0116] In any of the embodiments herein, R7 is a carbamate. In any of the embodiments herein,

[0117] In any of the embodiments herein, the compound of Formula O is INT-23:INT-23, or a salt thereof.

[0118] Disclosed herein is a compound of Formula P, or a salt thereof:Formula P, wherein each of R6and R7is an independently selected nitrogen protecting group.Attorney Docket No.: TGO-027WO

[0119] In any of the embodiments herein, R6 is a carbamate. In any of the embodiments herein,.

[0120] In any of the embodiments herein, R7 is a carbamate. In any of the embodiments herein,.

[0121] In any of the embodiments herein, the compound of Formula P is INT-15:INT-15, or a salt thereof.

[0122] Disclosed herein is a compound of Formula R, or a salt thereof:Formula R, wherein each of R6and R7is an independently selected nitrogen protecting group and R12is C1-C6alkyl. .

[0123] In any of the embodiments herein, R6 is a carbamate. In any of the embodiments herein,.

[0124] In any of the embodiments herein, R7 is a carbamate. In any of the embodiments herein,

[0125] In any of the embodiments herein, R12 is –Me, –Et, –nPr, –iPr, –nBu, or –tBu. In anyof the embodiments herein, R12is –Me. In any of the embodiments herein, R12is –Et. In any of the embodiments herein, R12is –nPr. In any of the embodiments herein, R12is –iPr. In any of the embodiments herein, R12is –nBu. In any of the embodiments herein, R12is –tBu.

[0126] In any of the embodiments herein, the compound of Formula R is INT-16:Attorney Docket No.: TGO-027WOINT-16, or a salt thereof.

[0127] In any of the embodiments herein, R8 is a nitrogen protecting group and R9 is a nitrogenprotecting group. In any of the embodiments herein, R8is a nitrogen protecting group and R9is H.

[0128] In any of the embodiments herein, R8 is a carbamate group and R9 is a carbamate group.In any of the embodiments herein, R8is a carbamate group and R9is a H. In any of the embodiments herein, R8is. In any of the embodiments herein, R8isand R9is H. In any of the embodiments herein, R8is R6and R9is R7.

[0129] In any of the embodiments herein, R8 is H and R9 isand the compound ofFormula I is:.

[0130] In any of the embodiments herein, R8 isand thecompound of Formula I is:Attorney Docket No.: TGO-027WO.

[0131] In any of the embodiments herein, R8 and R9 are each an independently selectednitrogen protecting group and the salt of the compound of Formula I is a formic acid salt of the compound of Formula I.

[0132] In any of the embodiments herein, R8 and R9 are each Boc, the salt is the formic acid,and the salt of the compound of Formula I is Compound A:Crystalline Form A of Compound A

[0133] In some embodiments, provided herein is a crystalline Form A of Compound A.References to “Form A” without additional modifiers refer to the crystalline Form A of Compound A.

[0134] Applicant has found, surprisingly, that the formic acid salt of the compound of FormulaI, particularly the Crystalline Form A of Compound A, is advantageous over other pharmaceutically acceptable salts in purifying a penultimate intermediate in the synthesis ofAttorney Docket No.: TGO-027WO the compound of Formula X. Form A of Compound A has crystallinity as evidenced by its X-ray Powder Diffraction pattern (XRPD) (FIG. 1).

[0135] In some embodiments, Form A has an X-ray powder diffraction pattern (obtained using CuKa radiation) comprising at least one (e.g., one, two, three, or four) characteristic peaks at values of 2θ in degrees selected from 11.6±0.2, 11.7±0.2, 14.5±0.2, 16.6±0.2, 17.2±0.2, 17.5±0.2, 17.6±0.2, 19±0.2, and 24.9±0.2. In some embodiments, Form A has an X-ray powder diffraction pattern comprising at least one characteristic peak at values of 2θ in degrees selected from 11.6±0.2, 11.7±0.2, 14.5±0.2, 16.6±0.2, 17.2±0.2, 17.5±0.2, 17.6±0.2, 19±0.2, and 24.9±0.2. In some embodiments, Form A has an X-ray powder diffraction pattern comprising at least two characteristic peaks at values of 2θ in degrees selected from 11.6±0.2, 11.7±0.2, 14.5±0.2, 16.6±0.2, 17.2±0.2, 17.5±0.2, 17.6±0.2, 19±0.2, and 24.9±0.2. In some embodiments, Form A has an X-ray powder diffraction pattern comprising at least three characteristic peaks at values of 2θ in degrees selected from 11.6±0.2, 11.7±0.2, 14.5±0.2, 16.6±0.2, 17.2±0.2, 17.5±0.2, 17.6±0.2, 19±0.2, and 24.9±0.2. In some embodiments, Form A has an X-ray powder diffraction pattern comprising characteristic peaks at values of 2θ in degrees of 11.6±0.2, 11.7±0.2, 14.5±0.2, 16.6±0.2, 17.2±0.2, 17.5±0.2, 17.6±0.2, 19±0.2, and 24.9±0.2.

[0136] In some embodiments, Form A has an XRPD pattern (obtained using CuKa radiation) substantially corresponding to the XRPD diffraction pattern shown in FIG.1.

[0137] In some embodiments, Form A has an XRPD pattern (obtained using CuKa radiation) with characteristic peaks comprising one, two, three, four, five, six, seven, eight, nine, or ten characteristic peaks, in terms of 2θ values in degrees shown in Table 1 (±0.2 degrees).

[0138] In some embodiments, Form A has an XRPD pattern (obtained using CuKa radiation) comprising at least 50% of the peaks at 2θ values in degrees and with relative intensities shown in Table 1 allowing for variation due to experimental conditions. Table 1Attorney Docket No.: TGO-027WO

[0139] In any of the embodiments herein, R8is H and R9is H.

[0140] In any of the embodiments herein, R8is H and R9is H, and the salt of the compound of Formula I is:Attorney Docket No.: TGO-027WO.

[0141] In any of the embodiments herein, R8 is H and R9 is H and the salt of the compound ofFormula I is selected from the phosphoric acid salt, the sulfuric acid salt, and the benzoic acid salt. In a preferred embodiment, R8is H and R9is H and the salt of the compound of Formula I is a phosphoric acid salt.

[0142] In any of the embodiments herein, R8 is H and R9 is H and the phosphoric acid salt ofthe compound of Formula I is Compound B:. Crystalline Form B of Compound B

[0143] In some embodiments, provided herein is a crystalline Form B of Compound B.References to “Form B” without additional modifiers refer to the crystalline Form B.

[0144] Applicant has found, surprisingly, that Crystalline Form B of Compound B isadvantageous over other pharmaceutically acceptable salts in purifying a penultimate intermediate in the synthesis of the compound of Formula X.

[0145] Form B of Compound B has crystallinity exhibited by its X-ray Powder Diffractionpattern (XRPD) (FIG.2).Attorney Docket No.: TGO-027WO

[0146] In some embodiments, Form B has an X-ray powder diffraction pattern (obtained using CuKa radiation) comprising at least one (e.g., one, two, three, or four) characteristic peaks at values of 2θ in degrees selected from 4.3±0.2, 8.6±0.2, 12.5±0.2, 15.5±0.2, 17±0.2, 17.6±0.2, 19.3±0.2, 21.4±0.2, 21.4±0.2, 23±0.2, 23.3±0.2, 24.5±0.2, and 27.3±0.2. In some embodiments, Form B has an X-ray powder diffraction pattern comprising at least one characteristic peak at values of 2θ in degrees selected from 4.3±0.2, 8.6±0.2, 12.5±0.2, 15.5±0.2, 17±0.2, 17.6±0.2, 19.3±0.2, 21.4±0.2, 21.4±0.2, 23±0.2, 23.3±0.2, 24.5±0.2, and 27.3±0.2. In some embodiments, Form B has an X-ray powder diffraction pattern comprising at least two characteristic peaks at values of 2θ in degrees selected from 4.3±0.2, 8.6±0.2, 12.5±0.2, 15.5±0.2, 17±0.2, 17.6±0.2, 19.3±0.2, 21.4±0.2, 21.4±0.2, 23±0.2, 23.3±0.2, 24.5±0.2, and 27.3±0.2. In some embodiments, Form B has an X-ray powder diffraction pattern comprising at least three characteristic peaks at values of 2θ in degrees selected from 4.3±0.2, 8.6±0.2, 12.5±0.2, 15.5±0.2, 17±0.2, 17.6±0.2, 19.3±0.2, 21.4±0.2, 21.4±0.2, 23±0.2, 23.3±0.2, 24.5±0.2, and 27.3±0.2. In some embodiments, Form B has an X-ray powder diffraction pattern comprising characteristic peaks at values of 2θ in degrees of 4.3±0.2, 8.6±0.2, 12.5±0.2, 15.5±0.2, 17±0.2, 17.6±0.2, 19.3±0.2, 21.4±0.2, 21.4±0.2, 23±0.2, 23.3±0.2, 24.5±0.2, and 27.3±0.2.

[0147] In some embodiments, Form B has an XRPD pattern (obtained using CuKa radiation) substantially corresponding to the XRPD diffraction pattern shown in FIG.2.

[0148] In some embodiments, Form B has an XRPD pattern (obtained using CuKa radiation) with characteristic peaks comprising one, two, three, four, five, six, seven, eight, nine, or ten characteristic peaks, in terms of 2θ values in degrees shown in Table 2 (±0.2 degrees).

[0149] In some embodiments, Form B has an XRPD pattern (obtained using CuKa radiation) comprising at least 50% of the peaks at 2θ values in degrees and with relative intensities shown in Table 2 allowing for variation due to experimental conditions. Table 2Attorney Docket No.: TGO-027WOAttorney Docket No.: TGO-027WOMethods of Preparing Compound

[0150] Provided herein are processes for preparing the compound of Formula X.

[0151] Also provided herein are processes for preparing the compounds of Formula B, Formula C, Formula D, Formula E, Formula F, Formula G, Formula H, Formula J, Formula K, Formula L, Formula M, Formula N, Formula O, Formula P, Formula R and salts thereof, which are useful as building blocks / intermediates in the synthesis of the compound of Formula X. Further provided herein are processes for preparing salts of the compounds of Formula I, which are useful as building blocks / intermediates in the synthesis of the compound of Formula X.

[0152] In some embodiments, the processes for preparing the compound of Formula X comprise one or more of the following synthetic steps: hydrogenation (e.g., hydrogenation mediated by chiral auxiliary) or amidation (e.g., enzymatic amidation); carbamate protection (e.g., Boc protection); cross-coupling; removal of carbamate protecting group (e.g., removing Boc group); reduction (e.g., hydride reduction or enzymatic reduction); coupling; and removal of one or more carbamate protecting groups (e.g., removing one or more Boc groups).

[0153] In some embodiments, the processes comprise one or more of the following synthetic steps: hydrogenation (e.g., hydrogenation mediated by chiral auxiliary); carbamate protection (e.g., Boc protection); cross-coupling; removal of carbamate protecting group (e.g., removing Boc group); reduction (e.g., hydride reduction); coupling; and removal of one or more carbamate protecting groups (e.g., removing one or more Boc groups).

[0154] In some embodiments, the processes comprise one or more of the following synthetic steps: hydrogenation (e.g., hydrogenation mediated by chiral auxiliary); carbamate protection (e.g., Boc protection); cross-coupling; removal of carbamate protecting group (e.g., removing Boc group); reduction (e.g., enzymatic reduction); coupling; and removal of one or more carbamate protecting groups (e.g., removing one or more Boc groups).

[0155] In some embodiments, the processes comprise one or more of the following synthetic steps: amidation (e.g., enzymatic amidation); carbamate protection (e.g., Boc protection); cross-coupling; removal of carbamate protecting group (e.g., removing Boc group); reductionAttorney Docket No.: TGO-027WO (e.g., hydride reduction); coupling; and removal of one or more carbamate protecting groups (e.g., removing one or more Boc groups).

[0156] In some embodiments, the processes comprise one or more of the following syntheticsteps: amidation (e.g., enzymatic amidation); carbamate protection (e.g., Boc protection); cross-coupling; removal of carbamate protecting group (e.g., removing Boc group); reduction (e.g., enzymatic reduction); coupling; and removal of one or more carbamate protecting groups (e.g., removing one or more Boc groups).

[0157] In some embodiments, the processes comprise hydrogenation (e.g., hydrogenationmediated by chiral auxiliary). In some embodiments, the processes comprise amidation (e.g., enzymatic amidation). In some embodiments, the processes comprise hydride reduction. In some embodiments, the processes comprise enzymatic reduction.

[0158] In any of the embodiments herein, the processes comprise one or more of the followingsynthetic steps: pivalamide protection, acetyl installation, carbonyl reduction, pivalamide deprotection, nitration, carbamate protection (e.g., Boc protection), nitro group reduction, oxalylamide installation, saponification.

[0159] In some embodiments, provided herein is a process for preparing the compound ofFormula X:Formula X, comprising: hydrogenating a compound of Formula A1:Formula A1, or a salt thereof, wherein R1is a chiral auxiliary, thereby producing a compound of Formula B:Attorney Docket No.: TGO-027WOFormula B, or a salt thereof; protecting the nitrogen of a compound of Formula B:Formula B, or a salt thereof, thereby producing a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group; cross-coupling a compound of Formula C:Formula C, or a salt thereof, with a compound of Formula D:or a salt thereof, wherein R3is a boronic acid or a boronic ester, thereby producing a compound of Formula E:or a salt thereof; removing nitrogen protecting group from a compound of Formula E:Attorney Docket No.: TGO-027WOor a salt thereof, thereby producing a compound of Formula F:Formula F, or a salt thereof; reducing a compound of Formula F:Formula F, or a salt thereof, thereby producing a compound of Formula G:Formula G, or a salt thereof; coupling a compound of Formula G:Attorney Docket No.: TGO-027WOor a salt thereof, with a compound of Formula H:or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, thereby producing a first salt of a compound of Formula I:wherein R8is R6and R9is R7; removing the nitrogen protecting groups from the first salt of a compound of Formula I:Attorney Docket No.: TGO-027WOwith a pharmaceutically acceptable acid, thereby producing a second salt of a compound of Formula I:Formula I, wherein each of R8and R9is H; and free-basing a second salt of a compound of Formula I:thereby producing the compound of Formula X.

[0160] In some embodiments, provided herein is a process for preparing the compound ofFormula X:Attorney Docket No.: TGO-027WOFormula X, comprising: hydrogenating a compound of Formula A1:Formula A1, or a salt thereof, wherein R1is a chiral auxiliary, thereby producing a compound of Formula B:Formula B, or a salt thereof; protecting the nitrogen of a compound of Formula B:Formula B, or a salt thereof, thereby producing a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group; cross-coupling a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group, with a compound of Formula D:Attorney Docket No.: TGO-027WOor a salt thereof, R3is a boronic acid or a boronic ester, thereby producing a compound of Formula E:or a salt thereof, wherein R2is a nitrogen protecting group; removing nitrogen protecting group from a compound of Formula E:or a salt thereof, wherein R2is a nitrogen protecting group, thereby producing a compound of Formula F:Formula F, or a salt thereof; enzymatically reducing a compound of Formula F:Attorney Docket No.: TGO-027WOor a salt thereof, thereby producing a compound of Formula G:Formula G, or a salt thereof; coupling a compound of Formula G:Formula G, or a salt thereof, with a compound of Formula H:Formula H, or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, thereby producing a first salt of a compound of Formula I:Attorney Docket No.: TGO-027WO wherein eachremoving the nitrogen protecting groups from a first salt of a compound of Formulawith a pharmaceutically acceptable acid, thereby producing a second salt of a compound of Formula I:Formula I, wherein each of R8and R9are each H; and free-basing a second salt of a compound of Formula I:Attorney Docket No.: TGO-027WOthereby producing the compound of Formula X.

[0161] In some embodiments, provided herein is a process for preparing the compound ofFormula X:or a salt thereof, comprising: enzymatically amidating a compound of Formula A2:Formula A2, or a salt thereof, wherein R11is C1-C6alkyl, thereby producing a compound of Formula B:Formula B, or a salt thereof; protecting the nitrogen of a compound of Formula B:Formula B,Attorney Docket No.: TGO-027WO or a salt thereof, thereby producing a compound of Formula C:or a salt thereof, wherein R2is a nitrogen protecting group; cross-coupling a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group, with a compound of Formula D:Formula D, or a salt thereof, wherein R3is a boronic acid or a boronic ester, thereby producing a compound of Formula E:or a salt thereof, wherein R2is a nitrogen protecting group; removing nitrogen protecting group from a compound of Formula E:or a salt thereof, wherein R2is a nitrogen protecting group, thereby producing a compound of Formula F:Attorney Docket No.: TGO-027WOFormula F, or a salt thereof; reducing a compound of Formula F:Formula F, or a salt thereof, thereby producing a compound of Formula G:Formula G, or a salt thereof; coupling a compound of Formula G:Formula G, or a salt thereof, with a compound of Formula H:Attorney Docket No.: TGO-027WOFormula H, or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, thereby producing a first salt of a compound of Formula I:wherein each of R8is R6and R9is R7; removing the nitrogen protecting groups from the first salt of a compound of Formula I:Formula I, with a pharmaceutically acceptable acid, thereby producing a second salt of a compound of Formula I:Attorney Docket No.: TGO-027WO wherein eachfree-basing a second salt of a compound of Formula I:thereby producing the compound of Formula X.

[0162] In some embodiments, provided herein is a process for preparing the compound ofFormula X:Formula X, comprising: enzymatically amidating a compound of Formula A2:Attorney Docket No.: TGO-027WOFormula A2, or a salt thereof, wherein R11isalkyl, thereby producing a compound of Formula B:Formula B, or a salt thereof; protecting the nitrogen of a compound of Formula B:Formula B, or a salt thereof, thereby producing a compound of Formula C:Formula C, or a salt thereof; cross-coupling a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group, with a compound of Formula D:or a salt thereof, wherein R3is a boronic acid or a boronic ester, thereby producing a compound of Formula E:Attorney Docket No.: TGO-027WOor a salt thereof, wherein R2is a nitrogen protecting group; removing nitrogen protecting group from a compound of Formula E:or a salt thereof, wherein R2is a nitrogen protecting group, thereby producing a compound of Formula F:or a salt thereof; enzymatically reducing a compound of Formula F:Formula F, or a salt thereof, thereby producing a compound of Formula G:Attorney Docket No.: TGO-027WOor a salt thereof; coupling a compound of Formula G:Formula G, or a salt thereof, with a compound of Formula H:or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, thereby producing a first salt of a compound of Formula I:Attorney Docket No.: TGO-027WO removing the nitrogen protecting groups from a first salt of a compound of Formulawherein each of R8and R9is H; and free-basing a second salt of a compound of Formula I:Formula I, thereby producing the compound of Formula X.

[0163] In some embodiments, the process further comprises:pivalamide protecting a compound of Formula J:Attorney Docket No.: TGO-027WOFormula J, or a salt thereof, thereby producing a compound of Formula K:or a salt thereof; installing an acetyl group on a compound of Formula K:Formula K, or a salt thereof, thereby producing a compound of Formula L:Formula L, or a salt thereof; reducing the carbonyl and pivalamide deprotecting of a compound of Formula L:Formula L, or a salt thereof, thereby producing a compound of Formula M:Formula M, or a salt thereof; nitrating a compound of Formula M:Attorney Docket No.: TGO-027WOor a salt thereof, thereby producing a compound of Formula N:Formula N, or a salt thereof; nitrogen protecting a compound of Formula N:Formula N, or a salt thereof, thereby producing a compound of Formula O:Formula O, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, nitro reducing a compound of Formula O:Formula O, or a salt thereof, thereby producing a compound of Formula P:Formula P, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, installing an oxalylamide on a compound of Formula P:Attorney Docket No.: TGO-027WOFormula P, or a salt thereof, thereby producing a compound of Formula R:Formula R, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group and R12is C1-C6 alkyl, saponifying a compound of Formula R:or a salt thereof, thereby producing a compound of Formula H:Formula H,

[0164] or a salt thereof; wherein R6 and R7 are each an independently selected nitrogenprotecting group.

[0165] In some embodiments, provided herein is a process for preparing the compound ofFormula X:Attorney Docket No.: TGO-027WOFormula X, comprising: hydrogenating a compound of Formula A1:Formula A1, or a salt thereof, wherein R1is a chiral auxiliary, thereby producing a compound of Formula B:Formula B, or a salt thereof; protecting the nitrogen of a compound of Formula B:Formula B, or a salt thereof, thereby producing a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group; cross-coupling a compound of Formula C:Formula C, or a salt thereof, with a compound of Formula D:Formula D, or a salt thereof, wherein R3is a boronic acid or a boronic ester,Attorney Docket No.: TGO-027WO thereby producing a compound of Formula E:or a salt thereof; removing nitrogen protecting group from a compound of Formula E:or a salt thereof, thereby producing a compound of Formula F:or a salt thereof; reducing a compound of Formula F:or a salt thereof, thereby producing a compound of Formula G:Attorney Docket No.: TGO-027WOFormula G, or a salt thereof; pivalamide protecting a compound of Formula J:Formula J, or a salt thereof, thereby producing a compound of Formula K:Formula K, or a salt thereof; installing an acetyl group on a compound of Formula K:Formula K, or a salt thereof, thereby producing a compound of Formula L:Formula L, or a salt thereof; reducing the carbonyl and pivalamide deprotecting of a compound of Formula L:Attorney Docket No.: TGO-027WO or a salt thereof, thereby producing a compound of Formula M:or a salt thereof; nitrating a compound of Formula M:or a salt thereof, thereby producing a compound of Formula N:Formula N, or a salt thereof; nitrogen protecting a compound of Formula N:Formula N, or a salt thereof, thereby producing a compound of Formula O:Formula O, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, nitro reducing a compound of Formula O:Formula O, or a salt thereof, thereby producing a compound of Formula P:Attorney Docket No.: TGO-027WOFormula P, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, installing an oxalylamide on a compound of Formula P:Formula P, or a salt thereof, thereby producing a compound of Formula R:Formula R, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group and R12is C1-C6alkyl, saponifying a compound of Formula R:thereby producing a compound of Formula H:or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, coupling a compound of Formula G:Attorney Docket No.: TGO-027WOFormula G, or a salt thereof, with a compound of Formula H:Formula H, or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, thereby producing a first salt of a compound of Formula I:Formula I, wherein R8is R6and R9is R7; removing the nitrogen protecting groups from the first salt of a compound of Formula I:Attorney Docket No.: TGO-027WOwith a pharmaceutically acceptable acid, thereby producing a second salt of a compound of Formula I:free-basing a second salt of a compound of Formula I:thereby producing the compound of Formula X.

[0166] In some embodiments, provided herein is a process for preparing the compound ofFormula X:Attorney Docket No.: TGO-027WOFormula X, comprising: hydrogenating a compound of Formula A1:Formula A1, or a salt thereof, wherein R1is a chiral auxiliary, thereby producing a compound of Formula B:Formula B, or a salt thereof; protecting the nitrogen of a compound of Formula B:Formula B, or a salt thereof, thereby producing a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group; cross-coupling a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group, with a compound of Formula D:Attorney Docket No.: TGO-027WOFormula D, or a salt thereof, R3is a boronic acid or a boronic ester, thereby producing a compound of Formula E:or a salt thereof, wherein R2is a nitrogen protecting group; removing nitrogen protecting group from a compound of Formula E:or a salt thereof, wherein R2is a nitrogen protecting group, thereby producing a compound of Formula F:or a salt thereof; enzymatically reducing a compound of Formula F:Attorney Docket No.: TGO-027WOFormula F, or a salt thereof, thereby producing a compound of Formula G:Formula G, or a salt thereof; pivalamide protecting a compound of Formula J:or a salt thereof, thereby producing a compound of Formula K:or a salt thereof; installing an acetyl group on a compound of Formula K:or a salt thereof, thereby producing a compound of Formula L:Attorney Docket No.: TGO-027WOFormula L, or a salt thereof; reducing the carbonyl and pivalamide deprotecting of a compound of Formula L:Formula L, or a salt thereof, thereby producing a compound of Formula M:or a salt thereof; nitrating a compound of Formula M:or a salt thereof, thereby producing a compound of Formula N:Formula N, or a salt thereof; nitrogen protecting a compound of Formula N:Formula N, or a salt thereof, thereby producing a compound of Formula O:Attorney Docket No.: TGO-027WOor a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, nitro reducing a compound of Formula O:Formula O, or a salt thereof, thereby producing a compound of Formula P:Formula P, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, installing an oxalylamide on a compound of Formula P:Formula P, or a salt thereof, thereby producing a compound of Formula R:Formula R, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group and R12is C1-C6alkyl, saponifying a compound of Formula R:Attorney Docket No.: TGO-027WO or a salt thereof, thereby producing a compound of Formula H:Formula H, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, : coupling a compound of Formula G:Formula G, or a salt thereof, with a compound of Formula H:Formula H, or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, thereby producing a first salt of a compound of Formula I:Attorney Docket No.: TGO-027WO removing the nitrogen protecting groups from a first salt of a compound of Formula I:Formula I, with a pharmaceutically acceptable acid, thereby producing a second salt of a compound of Formula I:Formula I, wherein each of R8and R9are each H; and free-basing a second salt of a compound of Formula I:Formula I, thereby producing the compound of Formula X.

[0167] In some embodiments, provided herein is a process for preparing the compound ofFormula X:Attorney Docket No.: TGO-027WOFormula X, or a salt thereof, comprising: enzymatically amidating a compound of Formula A2:Formula A2, or a salt thereof, wherein R11is C1-C6 alkyl, thereby producing a compound of Formula B:Formula B, or a salt thereof; protecting the nitrogen of a compound of Formula B:Formula B, or a salt thereof, thereby producing a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group; cross-coupling a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group,Attorney Docket No.: TGO-027WO with a compound of Formula D:Formula D, or a salt thereof, wherein R3is a boronic acid or a boronic ester, thereby producing a compound of Formula E:Formula E, or a salt thereof, wherein R2is a nitrogen protecting group; removing nitrogen protecting group from a compound of Formula E:Formula E, or a salt thereof, wherein R2is a nitrogen protecting group, thereby producing a compound of Formula F:Formula F, or a salt thereof; reducing a compound of Formula F:Attorney Docket No.: TGO-027WOFormula F, or a salt thereof, thereby producing a compound of Formula G:Formula G, or a salt thereof; pivalamide protecting a compound of Formula J:or a salt thereof, thereby producing a compound of Formula K:or a salt thereof; installing an acetyl group on a compound of Formula K:or a salt thereof, thereby producing a compound of Formula L:Attorney Docket No.: TGO-027WOFormula L, or a salt thereof; reducing the carbonyl and pivalamide deprotecting of a compound of Formula L:Formula L, or a salt thereof, thereby producing a compound of Formula M:or a salt thereof; nitrating a compound of Formula M:or a salt thereof, thereby producing a compound of Formula N:Formula N, or a salt thereof; nitrogen protecting a compound of Formula N:Formula N, or a salt thereof, thereby producing a compound of Formula O:Attorney Docket No.: TGO-027WOor a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, nitro reducing a compound of Formula O:Formula O, or a salt thereof, thereby producing a compound of Formula P:Formula P, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, installing an oxalylamide on a compound of Formula P:Formula P, or a salt thereof, thereby producing a compound of Formula R:Formula R, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group and R12is C1-C6alkyl, saponifying a compound of Formula R:Attorney Docket No.: TGO-027WO or a salt thereof, thereby producing a compound of Formula H:Formula H, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, coupling a compound of Formula G:or a salt thereof, with a compound of Formula H:Formula H, or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, thereby producing a first salt of a compound of Formula I:Attorney Docket No.: TGO-027WO removing the nitrogen protecting groups from the first salt of a compound of Formula I:Formula I, with a pharmaceutically acceptable acid, thereby producing a second salt of a compound of Formula I:free-basing a second salt of a compound of Formula I:Formula I, thereby producing the compound of Formula X.

[0168] In some embodiments, provided herein is a process for preparing the compound ofFormula X:Attorney Docket No.: TGO-027WOFormula X, comprising: enzymatically amidating a compound of Formula A2:Formula A2, or a salt thereof, wherein R11is C1-C6 alkyl, thereby producing a compound of Formula B:Formula B, or a salt thereof; protecting the nitrogen of a compound of Formula B:Formula B, or a salt thereof, thereby producing a compound of Formula C:Formula C, or a salt thereof; cross-coupling a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group,Attorney Docket No.: TGO-027WO with a compound of Formula D:Formula D, or a salt thereof, wherein R3is a boronic acid or a boronic ester, thereby producing a compound of Formula E:Formula E, or a salt thereof, wherein R2is a nitrogen protecting group; removing nitrogen protecting group from a compound of Formula E:Formula E, or a salt thereof, wherein R2is a nitrogen protecting group, thereby producing a compound of Formula F:Formula F, or a salt thereof; enzymatically reducing a compound of Formula F:Attorney Docket No.: TGO-027WOFormula F, or a salt thereof, thereby producing a compound of Formula G:Formula G, or a salt thereof; pivalamide protecting a compound of Formula J:or a salt thereof, thereby producing a compound of Formula K:or a salt thereof; installing an acetyl group on a compound of Formula K:or a salt thereof, thereby producing a compound of Formula L:Attorney Docket No.: TGO-027WOFormula L, or a salt thereof; reducing the carbonyl and pivalamide deprotecting of a compound of Formula L:Formula L, or a salt thereof, thereby producing a compound of Formula M:or a salt thereof; nitrating a compound of Formula M:or a salt thereof, thereby producing a compound of Formula N:Formula N, or a salt thereof; nitrogen protecting a compound of Formula N:Formula N, or a salt thereof, thereby producing a compound of Formula O:Attorney Docket No.: TGO-027WOor a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, nitro reducing a compound of Formula O:Formula O, or a salt thereof, thereby producing a compound of Formula P:Formula P, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, installing an oxalylamide on a compound of Formula P:Formula P, or a salt thereof, thereby producing a compound of Formula R:or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group and R12is C1-C6alkyl, saponifying a compound of Formula R:Attorney Docket No.: TGO-027WO or a salt thereof, thereby producing a compound of Formula H:Formula H, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, coupling a compound of Formula G:or a salt thereof, with a compound of Formula H:Formula H, or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, thereby producing a first salt of a compound of Formula I:Attorney Docket No.: TGO-027WO removing the nitrogen protecting groups from a first salt of a compound of FormulaFormula I, thereby producing a second salt of a compound of Formula I:Formula I, wherein each of R8and R9is H; and free-basing a second salt of a compound of Formula I:thereby producing the compound of Formula X. Enzyme Evolution

[0169] Enzymes are powerful protein catalysts that effect a wide range of chemicaltransformations with unrivaled efficiencies and selectivity. They are made from renewableAttorney Docket No.: TGO-027WO feedstocks, are biodegradable and can operate under ambient temperatures. The pharmaceutical industry, driven by the pressing need to deliver new and cost-effective medicines to patients, is quickly adopting the utilization of engineered enzymes for both synthesis of active compounds for lead generation, and manufacturing APIs.

[0170] Enzyme evolution is the process of recruitment and optimization of a preexisting activity in a protein scaffold, in order to achieve high catalytic efficiency and selectivity of a desired chemical transformation. Major developments in the biocatalysis field in the past 20 years have resulted in a rapid diversification of the enzymes that are available to the synthetic chemist, and these enzymes could serve as starting points of enzyme evolution. Combined with the increasingly lower cost of DNA sequencing and artificial gene synthesis, synthesizing genes is now a rapid and cost-effective way of generating novel enzymes for screening. Computational design and advanced protein engineering are the two major approaches to make new enzymes with diverse activities. Devine, P.N., et al., Extending the application of biocatalysis to meet the challenges of drug development. See, for example, Devine et al,. Extending the application of biocatalysis to meet the challenges of drug development. Nat. Rev. Chem. 2, 409–421 (2018); Turner et al., Directed evolution drives the next generation of biocatalysts. Nat Chem Biol., 2009, 5(8):567-73; Bornscheuer et al., Engineering the third wave of biocatalysis, Nature, 485, 185–194 (2012); and Hossack et al., Building Enzymes through Design and Evolution, ACS Catal.2023, 13, 19, 12436–12444.

[0171] For example, enzymes (e.g., ATA-22403 from STA Pharmaceutical Hong Kong Limited) can be used to catalyze the asymmetric amidation of esters (e.g., the compound of Formula A2, or a salt thereof) to amides (e.g., the compound of Formula B, or a salt thereof) and enzymes (e.g., IRED-23182 from STA Pharmaceutical Hong Kong Limited) can be used to catalyze the asymmetric hydrogenation of imines / enamines (e.g., the compound of Formula F, or a salt thereof) to amines (e.g., the compound of Formula G, or a salt thereof). In some embodiments, the processes described herein are performed with other naturally occurring or engineered enzymes capable of catalyzing certain reaction processes described herein (e.g., asymmetric amidation of esters to amides, asymmetric hydrogenation of imines / enamines to amines). Coupling

[0172] In some embodiments, provided herein is a process for preparing the compound of Formula X:Attorney Docket No.: TGO-027WOFormula X, comprising: coupling a compound of Formula G, or a salt thereof:Formula G,with a compound of Formula H, or a salt thereof:Formula H, wherein R6and R7are each an independently selected nitrogen protecting group according to any of the embodiments described herein, thereby producing a first salt of a compound of Formula I:Attorney Docket No.: TGO-027WO wherein R8is R6and R9is R7, followed by deprotecting the first salt of the compound of Formula I in the presence of a pharmaceutically acceptable acid to produce a second salt of the compound of Formula I:Formula I, wherein R8and R9are H, then free-basing the second salt of the compound of Formula I, thereby producing the compound of Formula X.

[0173] In any of the embodiments herein, coupling a compound of Formula G, or a salt thereof,with a compound of Formula H, or a salt thereof, comprises contacting the compound ofFormula G, or a salt thereof, with a compound of Formula H, or a salt thereof.

[0174] In any of the embodiments herein, coupling a compound of Formula G, or a salt thereof,with a compound of Formula H, or a salt thereof, comprises contacting the compound ofFormula G, or a salt thereof, with a compound of Formula H, or a salt thereof, having a molarratio of about 1:1 to about 1:1.2. In any of the embodiments herein, coupling a compound ofFormula G, or a salt thereof, with a compound of Formula H, or a salt thereof, comprisescontacting the compound of Formula G, or a salt thereof, with a compound of Formula H, ora salt thereof, having a molar ratio of about 1:1.1.

[0175] In any of the embodiments herein, coupling a compound of Formula G, or a salt thereof,with a compound of Formula H, or a salt thereof, comprises contacting the compound ofFormula G, or a salt thereof, with a compound of Formula H, or a salt thereof, in the presenceof a coupling reagent.

[0176] In any of the embodiments herein, the coupling reagent is an anhydride couplingreagent; a triazole-based coupling reagent; a carbodiimide coupling reagent; an imidazolium coupling reagent; a phosphonium salt coupling reagent; or a pyridinium salt coupling reagent. In any of the embodiments herein, the coupling reagent is a triazole-based coupling reagent. InAttorney Docket No.: TGO-027WO any of the embodiments herein, the coupling reagent is 1-[bis(dimethylamino)methylene]-1H- 1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU); N,N,N',N'- tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate (HBTU); O-(1H-6- chlorobenzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HCTU); or 2- (1H-benzotriazole-1-yl)-1,1,3,3-tetramethylaminium tetrafluoroborate (TBTU). In any of the embodiments herein, the coupling reagent is 1-[bis(dimethylamino)methylene]-1H-1,2,3- triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU) or 2-(1H-benzotriazole-1- yl)-1,1,3,3-tetramethylaminium tetrafluoroborate (TBTU). In any of the embodiments herein, the coupling reagent is 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethylaminium tetrafluoroborate (TBTU).

[0177] In any of the embodiments herein, the compound of Formula G, or a salt thereof, and the coupling reagent have a molar ratio of about 1:1 to about 1:2. In any of the embodiments herein, the compound of Formula G, or a salt thereof, and the coupling reagent have a molar ratio of about 1:1.5.

[0178] In any of the embodiments herein, coupling a compound of Formula G, or a salt thereof, with a compound of Formula H, or a salt thereof, comprises contacting the compound of Formula G, or a salt thereof, with a compound of Formula H, or a salt thereof, in the presence of a fifth base. In any of the embodiments herein, the fifth base is an organic base. In any of the embodiments herein, the fifth base is N-methylmorpholine (NMM).

[0179] In any of the embodiments herein, coupling a compound of Formula G, or a salt thereof, with a compound of Formula H, or a salt thereof, comprises contacting the compound of Formula G, or a salt thereof, with a compound of Formula H, or a salt thereof, in the presence of a ninth solvent. In any of the embodiments herein, the ninth solvent is a protic solvent. In any of the embodiments herein, the ninth solvent is acetonitrile.

[0180] In any of the embodiments herein, coupling a compound of Formula G, or a salt thereof, with a compound of Formula H, or a salt thereof, comprises contacting the compound of Formula G, or a salt thereof, with a compound of Formula H, or a salt thereof, in the presence of a tenth solvent. In any of the embodiments herein, the tenth solvent is a polar solvent. In any of the embodiments herein, the tenth solvent is an ether solvent. In any of the embodiments herein, the tenth solvent is methyl tert-butyl ether.

[0181] In any of the embodiments herein, coupling a compound of Formula G, or a salt thereof, with a compound of Formula H, or a salt thereof, comprises contacting the compound ofAttorney Docket No.: TGO-027WO Formula G with a compound of Formula H, or a salt thereof, in the presence of a third acid. In any of the embodiments herein, the third acid is formic acid.

[0182] In any of the embodiments herein, coupling a compound of Formula G, or a salt thereof,with a compound of Formula H, or a salt thereof, results in a first salt of a compound of Formula I. In some embodiments, the first salt of the compound of Formula I is a crystalline salt of the first salt of the compound of Formula I.

[0183] In any of the embodiments herein, the first salt of the compound of Formula I isCompound A:Compound A.

[0184] In any of the embodiments herein, Compound A is a crystalline form (Form A) ofCompound A as made according to the example below.

[0185] In any of the embodiments herein, Form A of Compound A has crystallinity asevidenced by its X-ray Powder Diffraction pattern (XRPD) (FIG.1).

[0186] In any of the embodiments herein, Form A has an X-ray powder diffraction pattern(obtained using CuKa radiation) comprising at least one (e.g., one, two, three, or four) characteristic peaks at values of 2θ in degrees selected from 11.6±0.2, 11.7±0.2, 14.5±0.2, 16.6±0.2, 17.2±0.2, 17.5±0.2, 17.6±0.2, 19±0.2, and 24.9±0.2. In any of the embodiments herein, Form A has an X-ray powder diffraction pattern comprising at least one characteristic peak at values of 2θ in degrees selected from 11.6±0.2, 11.7±0.2, 14.5±0.2, 16.6±0.2, 17.2±0.2, 17.5±0.2, 17.6±0.2, 19±0.2, and 24.9±0.2. In any of the embodiments herein, Form A has an X-ray powder diffraction pattern comprising at least two characteristic peaks at values of 2θ in degrees selected from 11.6±0.2, 11.7±0.2, 14.5±0.2, 16.6±0.2, 17.2±0.2, 17.5±0.2, 17.6±0.2, 19±0.2, and 24.9±0.2. In any of the embodiments herein, Form A has an X-ray powder diffraction pattern comprising at least three characteristic peaks at values of 2θ in degrees selected from 11.6±0.2, 11.7±0.2, 14.5±0.2, 16.6±0.2, 17.2±0.2, 17.5±0.2, 17.6±0.2, 19±0.2,Attorney Docket No.: TGO-027WO and 24.9±0.2. In any of the embodiments herein, Form A has an X-ray powder diffraction pattern comprising characteristic peaks at values of 2θ in degrees of 11.6±0.2, 11.7±0.2, 14.5±0.2, 16.6±0.2, 17.2±0.2, 17.5±0.2, 17.6±0.2, 19±0.2, and 24.9±0.2.

[0187] In any of the embodiments herein, Form A has an XRPD pattern (obtained using CuKa radiation) with characteristic peaks comprising one, two, three, four, five, six, seven, eight, nine, or ten characteristic peaks, in terms of 2θ values in degrees shown in Table 1 (±0.2 degrees).

[0188] In any of the embodiments herein, Form A has an XRPD pattern (obtained using CuKa radiation) comprising at least 50% of the peaks at 2θ values in degrees and with relative intensities shown in Table 1 allowing for variation due to experimental conditions. Table 1Attorney Docket No.: TGO-027WO

[0189] In an alternative of any of these embodiments, the compound of Formula G, or a saltthereof, is present in more than about 80% by weight or by mole fraction, more than about 85% by weight or by mole fraction, more than about 90% by weight or by mole fraction, more than about 91% by weight or by mole fraction, more than about 92% by weight or by mole fraction, more than about 93% by weight or by mole fraction, more than about 94% by weight or by mole fraction, more than about 95% by weight or by mole fraction, more than about 96% by weight or by mole fraction, more than about 97% by weight or by mole fraction, more than about 98% by weight or by mole fraction, more than about 98.5% by weight or by mole fraction, more than about 99% by weight or by mole fraction, more than about 99.1% by weight or by mole fraction, more than about 99.2% by weight or by mole fraction, more than about 99.3% by weight or by mole fraction, more than about 99.4% by weight or by mole fraction, more than about 99.5% by weight or by mole fraction, more than about 99.6% by weight or by mole fraction, more than about 99.7% by weight or by mole fraction, more than about 99.8% by weight or by mole fraction, more than about 99.9% by weight or by mole fraction, of the diastereomer: .Attorney Docket No.: TGO-027WO Second Nitrogen Deprotection

[0190] In some embodiments, provided herein is a process for preparing the compound ofFormula X:comprising: removing one or more nitrogen protecting groups from a first salt of a compound of Formula I:Formula I, wherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group, thereby producing a second salt of a compound of Formula I:Attorney Docket No.: TGO-027WO wherein eachconverting the second salt of the compound of Formula I to the compound of Formula X.

[0191] In any of the embodiments herein, the process further comprises removing one or morenitrogen protecting groups from a first salt of a compound of Formula I:wherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group, thereby producing a second salt of a compound of Formula I:Attorney Docket No.: TGO-027WO wherein each of R8and R9is H; and converting the second salt of the compound of Formula I to the compound of Formula X.

[0192] In any of the embodiments herein, removing one or more nitrogen protecting groupsfrom a first salt of a compound of Formula I comprises contacting the first salt of the compound of Formula I, with a fourth acid. In any of the embodiments herein, the fourth acid is an inorganic acid. In any of the embodiments herein, the fourth acid is hydrochloric acid (HCl), sulfuric acid (H2SO4), benzoic acid, or phosphoric acid (H3PO4). In any of the embodiments herein, the fourth acid is phosphoric acid (H3PO4).

[0193] In any of the embodiments herein, removing one or more nitrogen protecting groupsfrom a first salt of a compound of Formula I comprises contacting the first salt of the compound of Formula I with an eleventh solvent. In any of the embodiments herein, the eleventh solvent is a polar solvent. In any of the embodiments herein, the eleventh solvent is acetone.

[0194] In any of the embodiments herein, removing one or more nitrogen protecting groupsfrom a first salt of a compound of Formula I results in a second salt of a compound of Formula I. In some embodiments, the second salt of the compound of Formula I is a crystalline salt of the second salt of the compound of Formula I.

[0195] In any of the embodiments herein, the second salt of the compound of Formula I,wherein each of R8and R9is H, is a crystalline form of a phosphoric acid salt of the compound of Formula I.

[0196] In any of the embodiments herein, the second salt of the compound of Formula I isCompound B:Compound B.

[0197] In any of the embodiments herein, Compound B is a crystalline form (Form B) ofCompound B as made according to the example below.

[0198] Form B of Compound B has crystallinity exhibited by its X-ray Powder Diffractionpattern (XRPD) (FIG.2).Attorney Docket No.: TGO-027WO

[0199] In any of the embodiments herein, Form B has an X-ray powder diffraction pattern (obtained using CuKa radiation) comprising at least one (e.g., one, two, three, or four) characteristic peaks at values of 2θ in degrees selected from 4.3±0.2, 8.6±0.2, 12.5±0.2, 15.5±0.2, 17±0.2, 17.6±0.2, 19.3±0.2, 21.4±0.2, 21.4±0.2, 23±0.2, 23.3±0.2, 24.5±0.2, and 27.3±0.2. In any of the embodiments herein, Form B has an X-ray powder diffraction pattern comprising at least one characteristic peak at values of 2θ in degrees selected from 4.3±0.2, 8.6±0.2, 12.5±0.2, 15.5±0.2, 17±0.2, 17.6±0.2, 19.3±0.2, 21.4±0.2, 21.4±0.2, 23±0.2, 23.3±0.2, 24.5±0.2, and 27.3±0.2. In any of the embodiments herein, Form B has an X-ray powder diffraction pattern comprising at least two characteristic peaks at values of 2θ in degrees selected from 4.3±0.2, 8.6±0.2, 12.5±0.2, 15.5±0.2, 17±0.2, 17.6±0.2, 19.3±0.2, 21.4±0.2, 21.4±0.2, 23±0.2, 23.3±0.2, 24.5±0.2, and 27.3±0.2. In any of the embodiments herein, Form B has an X-ray powder diffraction pattern comprising at least three characteristic peaks at values of 2θ in degrees selected from 4.3±0.2, 8.6±0.2, 12.5±0.2, 15.5±0.2, 17±0.2, 17.6±0.2, 19.3±0.2, 21.4±0.2, 21.4±0.2, 23±0.2, 23.3±0.2, 24.5±0.2, and 27.3±0.2. In any of the embodiments herein, Form B has an X-ray powder diffraction pattern comprising characteristic peaks at values of 2θ in degrees of 4.3±0.2, 8.6±0.2, 12.5±0.2, 15.5±0.2, 17±0.2, 17.6±0.2, 19.3±0.2, 21.4±0.2, 21.4±0.2, 23±0.2, 23.3±0.2, 24.5±0.2, and 27.3±0.2.

[0200] In any of the embodiments herein, Form B has an XRPD pattern (obtained using CuKa radiation) with characteristic peaks comprising one, two, three, four, five, six, seven, eight, nine, or ten characteristic peaks, in terms of 2θ values in degrees shown in Table 2 (±0.2 degrees).

[0201] In any of the embodiments herein, Form B has an XRPD pattern (obtained using CuKa radiation) comprising at least 50% of the peaks at 2θ values in degrees and with relative intensities shown in Table 2 allowing for variation due to experimental conditions. Table 2Attorney Docket No.: TGO-027WOAttorney Docket No.: TGO-027WOFree-Basing

[0202] In some embodiments, provided herein is a process for preparing the compound ofFormula X:Formula X, comprising: free-basing a second salt of a compound of Formula I:Formula I, wherein each of R8and R9is H, thereby producing the compound of Formula X:Attorney Docket No.: TGO-027WOFormula X.

[0203] In any of the embodiments herein, the process further comprises free-basing a secondsalt of a compound of Formula I:Formula I, wherein each of R8and R9is H, thereby producing the compound of Formula X:

[0204] In some embodiments, the second salt of the compound of Formula I is neutralizedwith Na2CO3aqueous solution, and the crude compound of Formula X is extracted out with a solvent mixture of 2-methyl tetrahydrofuran (2-MeTHF) / tetrahydrofuran (THF). In some embodiments, a solvent switch to methyl ethyl ketone (MEK) is used to crystallize theAttorney Docket No.: TGO-027WO compound of Formula X from MEK and n-Heptane, followed by wet-milling. The compound of Formula X is isolated via filtration and dried to meet the ICH Q3C Guidance for residual solvents.

[0205] In any of the embodiments herein, the second salt of the compound of Formula I iscontacted with a twelfth solvent. In any of the embodiments herein, the twelfth solvent is an apolar solvent. In any of the embodiments herein, the twelfth solvent is n-heptane.

[0206] In any of the embodiments herein, the second salt of the compound of Formula I iscontacted with a sixth base. In any of the embodiments herein, the sixth base is a carbonate base. In any of the embodiments herein, the sixth base is Na2CO3.

[0207] In any of the embodiments herein, the second salt of the compound of Formula I iscontacted with a thirteenth solvent. In any of the embodiments herein, the thirteenth solvent is a polar solvent. In any of the embodiments herein, the thirteenth solvent is a ketone solvent. In any of the embodiments herein, the thirteenth solvent is methyl ethyl ketone (MEK). Non-enzymatic Reduction

[0208] In any of the embodiments herein, the compound of Formula G, or a salt thereof, maybe prepared by non-enzymatic reduction. As used herein, the term “reducing” without any additional qualifiers refers to a non-enzymatic reduction. Thus, in any of the embodiments herein, a compound of Formula G:Formula G,or a salt thereof, is prepared by a process comprising: reducing a compound of Formula F:Formula F,or a salt thereof, thereby producing a compound of Formula G, or a salt thereof.Attorney Docket No.: TGO-027WO

[0209] In any of the embodiments herein, reducing a compound of Formula F comprisescontacting the compound of Formula F with a reducing agent. In any of the embodiments herein, the reducing agent is a hydride reducing agent. In any of the embodiments herein, the reducing agent is a borohydride reducing agent. In any of the embodiments herein, the reducing agent is sodium borohydride (NaBH4).

[0210] In any of the embodiments herein, reducing a compound of Formula F comprisescontacting the compound of Formula F with an eighth solvent. In any of the embodiments herein, the eighth solvent is a protic solvent. In any of the embodiments herein, the eighth solvent is methanol (MeOH).

[0211] In any of the embodiments herein, the compound depicted by Formula G, or a saltthereof, is prepared as more than about 80% by weight or by mole fraction, more than about 85% by weight or by mole fraction, more than about 90% by weight or by mole fraction, more than about 91% by weight or by mole fraction, more than about 92% by weight or by mole fraction, more than about 93% by weight or by mole fraction, more than about 94% by weight or by mole fraction, more than about 95% by weight or by mole fraction, more than about 96% by weight or by mole fraction, more than about 97% by weight or by mole fraction, more than about 98% by weight or by mole fraction, more than about 98.5% by weight or by mole fraction, more than about 99% by weight or by mole fraction, more than about 99.1% by weight or by mole fraction, more than about 99.2% by weight or by mole fraction, more than about 99.3% by weight or by mole fraction, more than about 99.4% by weight or by mole fraction, more than about 99.5% by weight or by mole fraction, more than about 99.6% by weight or by mole fraction, more than about 99.7% by weight or by mole fraction, more than about 99.8% by weight or by mole fraction, more than about 99.9% by weight or by mole fraction, of the diastereomer:or a salt thereof, compared to any of the other diastereomers of Formula G, or salts thereof.Attorney Docket No.: TGO-027WO Enzymatic Reduction

[0212] In any of the embodiments herein, the compound of Formula G, or a salt thereof, mayalternatively be prepared by enzymatic reduction. Thus, in any of the embodiments herein, the compound of Formula G is prepared by enzymatically reducing a compound of Formula F:Formula F, or a salt thereof, thereby producing a compound of Formula G:Formula G,or a salt thereof.

[0213] In any of the embodiments herein, enzymatically reducing a compound of Formula Fcomprises contacting the compound of Formula F with a third enzyme. In any of the embodiments herein, the third enzyme is an imine reductase. In any of the embodiments herein, the third enzyme is a naturally occurring (wild-type) imine reductase. In any of the embodiments herein, the third enzyme is an engineered imine reductase capable of catalyzing the reducing of a compound of Formula F to a compound of Formula G. In any of the embodiments herein, the third enzyme is IRED-23182.

[0214] In any of the embodiments herein, enzymatically reducing a compound of Formula Fcomprises contacting the compound of Formula F with a fourth enzyme. In any of the embodiments herein, the fourth enzyme is a glutamate dehydrogenase.

[0215] In any of the embodiments herein, enzymatically reducing a compound of Formula Fcomprises contacting the compound of Formula F with nicotinamide adenine dinucleotide phosphate (NADP).Attorney Docket No.: TGO-027WO

[0216] In any of the embodiments herein, enzymatically reducing a compound of Formula Fcomprises contacting the compound of Formula F comprises contacting the compound of Formula F with a sugar. In any of the embodiments herein, the sugar is glucose.

[0217] In any of the embodiments herein, enzymatically reducing a compound of Formula Fcomprises contacting the compound of Formula F comprises contacting the compound of Formula F with a buffer. In any of the embodiments herein, the buffer comprises K2HPO4. In any of the embodiments herein, the buffer comprises KH2PO4. In any of the embodiments herein, the buffer comprises K2HPO4and KH2PO4.

[0218] In any of the embodiments herein, the compound depicted by Formula G, or a saltthereof, is prepared as more than about 80% by weight or by mole fraction, more than about 85% by weight or by mole fraction, more than about 90% by weight or by mole fraction, more than about 91% by weight or by mole fraction, more than about 92% by weight or by mole fraction, more than about 93% by weight or by mole fraction, more than about 94% by weight or by mole fraction, more than about 95% by weight or by mole fraction, more than about 96% by weight or by mole fraction, more than about 97% by weight or by mole fraction, more than about 98% by weight or by mole fraction, more than about 98.5% by weight or by mole fraction, more than about 99% by weight or by mole fraction, more than about 99.1% by weight or by mole fraction, more than about 99.2% by weight or by mole fraction, more than about 99.3% by weight or by mole fraction, more than about 99.4% by weight or by mole fraction, more than about 99.5% by weight or by mole fraction, more than about 99.6% by weight or by mole fraction, more than about 99.7% by weight or by mole fraction, more than about 99.8% by weight or by mole fraction, more than about 99.9% by weight or by mole fraction, of the diastereomer:or a salt thereof, compared to any of the other diastereomers of Formula G, or salts thereof. First Nitrogen Deprotection

[0219] In any of the embodiments herein, a compound of Formula F:Attorney Docket No.: TGO-027WOor a salt thereof, is prepared by removing the nitrogen protecting group R2from a compound of Formula E:Formula E, or a salt thereof, wherein R2is a nitrogen protecting group according to any of the embodiments described herein, thereby producing a compound of Formula F, or a salt thereof.

[0220] In any of the embodiments herein, removing nitrogen protecting group from acompound of Formula E comprises contacting the compound of Formula E with a first acid. In any of the embodiments herein, the first acid is an inorganic acid. In any of the embodiments herein, the first acid is hydrochloric acid.

[0221] In any of the embodiments herein, removing nitrogen protecting group from acompound of Formula E comprises contacting the compound of Formula E with a seventh solvent. In any of the embodiments herein, the seventh solvent is a protic solvent. In any of the embodiments herein, the seventh solvent is an alcohol. In any of the embodiments herein, the seventh solvent is methanol (MeOH).

[0222] In any of the embodiments herein, the compound depicted by Formula F, or a saltthereof, is produced as a mixture comprising more than about 80% by weight or by mole fraction, more than about 85% by weight or by mole fraction, more than about 90% by weight or by mole fraction, more than about 91% by weight or by mole fraction, more than about 92% by weight or by mole fraction, more than about 93% by weight or by mole fraction, more than about 94% by weight or by mole fraction, more than about 95% by weight or by mole fraction, more than about 96% by weight or by mole fraction, more than about 97% by weight or byAttorney Docket No.: TGO-027WO mole fraction, more than about 98% by weight or by mole fraction, more than about 98.5% by weight or by mole fraction, more than about 99% by weight or by mole fraction, more than about 99.1% by weight or by mole fraction, more than about 99.2% by weight or by mole fraction, more than about 99.3% by weight or by mole fraction, more than about 99.4% by weight or by mole fraction, more than about 99.5% by weight or by mole fraction, more than about 99.6% by weight or by mole fraction, more than about 99.7% by weight or by mole fraction, more than about 99.8% by weight or by mole fraction, more than about 99.9% by weight or by mole fraction, of the enantiomer:,or a salt thereof, compared to the enantiomer:,or a salt thereof. Cross-Coupling

[0223] In any of the embodiments herein, a compound of Formula E, or a salt thereof, may beprepared by cross-coupling a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group according to any of the embodiments described herein, with a compound of Formula D:Attorney Docket No.: TGO-027WOFormula D, or a salt thereof, wherein R3is a boronic acid or a boronic ester according to any of the embodiments described herein, thereby producing a compound of Formula E, or a salt thereof.

[0224] In any of the embodiments herein, the compound depicted by Formula E, or a saltthereof, is produced as a mixture comprising more than about 80% by weight or by mole fraction, more than about 85% by weight or by mole fraction, more than about 90% by weight or by mole fraction, more than about 91% by weight or by mole fraction, more than about 92% by weight or by mole fraction, more than about 93% by weight or by mole fraction, more than about 94% by weight or by mole fraction, more than about 95% by weight or by mole fraction, more than about 96% by weight or by mole fraction, more than about 97% by weight or by mole fraction, more than about 98% by weight or by mole fraction, more than about 98.5% by weight or by mole fraction, more than about 99% by weight or by mole fraction, more than about 99.1% by weight or by mole fraction, more than about 99.2% by weight or by mole fraction, more than about 99.3% by weight or by mole fraction, more than about 99.4% by weight or by mole fraction, more than about 99.5% by weight or by mole fraction, more than about 99.6% by weight or by mole fraction, more than about 99.7% by weight or by mole fraction, more than about 99.8% by weight or by mole fraction, more than about 99.9% by weight or by mole fraction, in the mixture of the enantiomer:or a salt thereof, compared to the enantiomer:Attorney Docket No.: TGO-027WOor a salt thereof.

[0225] In any of the embodiments herein, cross-coupling a compound of Formula C, or a saltthereof with a compound of Formula D, or a salt thereof, comprises converting the compoundof Formula C, or the salt thereof, to a compound of Formula C-1:Formula C-1, or a salt thereof, wherein R2is a nitrogen protecting group according to any of the embodiments described herein, and R4is an alkyl sulfonate, a haloalkyl sulfonate, or an aryl sulfonate.

[0226] In any of the embodiments herein, the conversion of the compound of Formula C, ora salt thereof, to a compound of Formula C-1, or a salt thereof, comprises contacting thecompound of Formula C, or the salt thereof, with a dehydrating agent. In any of theembodiments herein, the dehydrating agent is a sulfonimide. In any of the embodiments herein, the dehydrating agent is 1,1,1-trifluoro-N-phenyl-N-(trifluoromethanesulfonyl) methanesulfonamide (PhNTf2).

[0227] In any of the embodiments herein, converting the compound of Formula C, or a saltthereof, to a compound of Formula C-1, or a salt thereof, comprises contacting the compoundof Formula C, or a salt thereof, with a third base. In any of the embodiments herein, the thirdbase is an inorganic base. In any of the embodiments herein, the third base is an organic base. In any of the embodiments herein, the third base is a lithium base. In any of the embodiments herein, the third base is an amine base. In any of the embodiments herein, the third base is lithium bis(trimethylsilyl)amide (LiHMDS).

[0228] In any of the embodiments herein, converting the compound of Formula C, or a saltthereof, to a compound of Formula C-1, or a salt thereof, comprises contacting the compoundof Formula C, or the salt thereof, with a fourth solvent. In any of the embodiments herein, theAttorney Docket No.: TGO-027WO fourth solvent is a polar solvent. In any of the embodiments herein, the fourth solvent is tetrahydrofuran (THF).

[0229] In any of the embodiments herein, converting the compound of Formula C, or a salt thereof, to a compound of Formula C-1, or a salt thereof, comprises lowering reaction temperature to below about 0 ºC. In any of the embodiments herein, converting the compound of Formula C, or a salt thereof, to a compound of Formula C-1, or a salt thereof, comprises lowering reaction temperature to about -20 ºC to about -10 °C.

[0230] In any of the embodiments herein, cross-coupling a compound of Formula C, or a salt thereof, with a compound of Formula D, or a salt thereof, comprises contacting a compound of Formula C-1, or a salt thereof, with a compound of Formula D, or a salt thereof.

[0231] In any of the embodiments herein, cross-coupling a compound of Formula C, or a salt thereof, with a compound of Formula D, or a salt thereof, comprises contacting a compound of Formula C-1, or a salt thereof, with the compound of Formula D, or a salt thereof.

[0232] In any of the embodiments herein, cross-coupling a compound of Formula C, or a salt thereof, with a compound of Formula D, or a salt thereof, comprises contacting a compound of Formula C-1, or a salt thereof, with the compound of Formula D, or a salt thereof, in the presence of a second catalyst.

[0233] In any of the embodiments herein, cross-coupling a compound of Formula C, or a salt thereof, with a compound of Formula D, or a salt thereof, comprises contacting a compound of Formula C-1, or a salt thereof, with the compound of Formula D, or a salt thereof, in the presence of less than about 10 mol% of the second catalyst. In any of the embodiments herein, cross-coupling a compound of Formula C, or a salt thereof, with a compound of Formula D, or a salt thereof, comprises contacting a compound of Formula C-1, or a salt thereof, with the compound of Formula D, or a salt thereof, in the presence of less than about 5 mol% of the second catalyst. In any of the embodiments herein, cross-coupling a compound of Formula C, or a salt thereof, with a compound of Formula D, or a salt thereof, comprises contacting a compound of Formula C-1, or a salt thereof, with the compound of Formula D, or a salt thereof, in the presence of about 5 mol% of the second catalyst. In any of the embodiments herein, cross-coupling a compound of Formula C, or a salt thereof, with a compound of Formula D, or a salt thereof, comprises contacting a compound of Formula C-1, or a salt thereof, with the compound of Formula D, or a salt thereof, in the presence of about 4.5 mol% of the second catalyst. In any of the embodiments herein, cross-coupling a compound of Formula C, or a salt thereof, with a compound of Formula D, or a salt thereof, comprisesAttorney Docket No.: TGO-027WO contacting a compound of Formula C-1, or a salt thereof, with the compound of Formula D, or a salt thereof, in the presence of about 4 mol% of the second catalyst. In any of the embodiments herein, cross-coupling a compound of Formula C, or a salt thereof, with a compound of Formula D, or a salt thereof, comprises contacting a compound of Formula C- 1, or a salt thereof, with the compound of Formula D, or a salt thereof, in the presence of about 3.5 mol% of the second catalyst. In any of the embodiments herein, cross-coupling a compound of Formula C, or a salt thereof, with a compound of Formula D, or a salt thereof, comprises contacting a compound of Formula C-1, or a salt thereof, with the compound of Formula D, or a salt thereof, in the presence of about 3 mol% of the second catalyst. In any of the embodiments herein, cross-coupling a compound of Formula C, or a salt thereof, with a compound of Formula D, or a salt thereof, comprises contacting a compound of Formula C- 1, or a salt thereof, with the compound of Formula D, or a salt thereof, in the presence of about 2.5 mol% of the second catalyst.

[0234] In any of the embodiments herein, the second catalyst is a palladium catalyst. In any of the embodiments herein, the second catalyst is a palladium (II) catalyst. In any of the embodiments herein, the second catalyst is [1,1'- bis(diphenylphosphino)ferrocene]dichloropalladium(II).

[0235] In any of the embodiments herein, cross-coupling a compound of Formula C, or a salt thereof, with a compound of Formula D, or a salt thereof, comprises contacting a compound of Formula C-1, or a salt thereof, with the compound of Formula D, or a salt thereof, in the presence of a fourth base. In any of the embodiments herein, the fourth base is an inorganic base. In any of the embodiments herein, the fourth base is a carbonate base. In any of the embodiments herein, the fourth base is Na2CO3.

[0236] In any of the embodiments herein, cross-coupling a compound of Formula C, or a salt thereof, with a compound of Formula D, or a salt thereof, comprises contacting a compound of Formula C-1, or a salt thereof, with the compound of Formula D, or a salt thereof, in the presence of a fifth solvent. In any of the embodiments herein, the fifth solvent is a polar solvent. In any of the embodiments herein, the fifth solvent is tetrahydrofuran (THF).

[0237] In any of the embodiments herein, cross-coupling a compound of Formula C, or a salt thereof, with a compound of Formula D, or a salt thereof, comprises contacting a compound of Formula C-1, or a salt thereof, with the compound of Formula D, or a salt thereof, in the presence of a sixth solvent. In any of the embodiments herein, the sixth solvent is water.Attorney Docket No.: TGO-027WO

[0238] In any of the embodiments herein, the compound depicted by Formula C-1, or a saltthereof, is produced as a mixture comprising more than about 80% by weight or by mole fraction, more than about 85% by weight or by mole fraction, more than about 90% by weight or by mole fraction, more than about 91% by weight or by mole fraction, more than about 92% by weight or by mole fraction, more than about 93% by weight or by mole fraction, more than about 94% by weight or by mole fraction, more than about 95% by weight or by mole fraction, more than about 96% by weight or by mole fraction, more than about 97% by weight or by mole fraction, more than about 98% by weight or by mole fraction, more than about 98.5% by weight or by mole fraction, more than about 99% by weight or by mole fraction, more than about 99.1% by weight or by mole fraction, more than about 99.2% by weight or by mole fraction, more than about 99.3% by weight or by mole fraction, more than about 99.4% by weight or by mole fraction, more than about 99.5% by weight or by mole fraction, more than about 99.6% by weight or by mole fraction, more than about 99.7% by weight or by mole fraction, more than about 99.8% by weight or by mole fraction, more than about 99.9% by weight or by mole fraction, of the enantiomer:, or a salt thereof, over the other enantiomer, or a salt thereof. Nitrogen Protection

[0239] In any of the embodiments herein, a compound of Formula C, or a salt thereof, is beprepared by protecting the nitrogen of a compound of Formula B:Formula B, or a salt thereof, thereby producing a compound of Formula C:Attorney Docket No.: TGO-027WOFormula C, or a salt thereof, wherein R2is a nitrogen protecting group according to any of the embodiments described herein.

[0240] In any of the embodiments herein, nitrogen protection of a compound of Formula B, or a salt thereof, comprises contacting the compound of Formula B with a first nitrogen protecting group reagent. In any of the embodiments herein, the first nitrogen protecting group reagent comprises a carbamate. In any of the embodiments herein, the first nitrogen protecting group reagent comprises . In any of the embodiments herein, the first nitrogen protecting group reagent is .In any of the embodiments herein, protectingthe nitrogen of a compound of Formula B, or a salt thereof, comprises contacting the compound of Formula B, or the salt thereof, with a first base. In any of the embodiments herein, the first base is a pyridine base. In any of the embodiments herein, the first base is dimethylaminopyridine (DMAP).

[0241] In any of the embodiments herein, protecting the nitrogen of a compound of Formula B, or a salt thereof, comprises contacting the compound of Formula B, or the salt thereof, with a second base. In any of the embodiments herein, the second base is an amine base. In any of the embodiments herein, the second base is triethylamine (TEA).

[0242] In any of the embodiments herein, protecting the nitrogen of a compound of Formula B, or a salt thereof, comprises contacting the compound of Formula B, or the salt thereof, with a third solvent. In any of the embodiments herein, the third solvent is a polar solvent. In any of the embodiments herein, the third solvent is acetonitrile. In any of the embodiments herein, the third solvent is a halogenated solvent. In any of the embodiments herein, the third solvent is dichloromethane (DCM).

[0243] In any of the embodiments herein, protecting the nitrogen of a compound of Formula B, or a salt thereof, comprises elevating reaction temperature to about 40 °C to about 50 °C. In any of the embodiments herein, protecting the nitrogen of a compound of Formula B, or a salt thereof, comprises elevating reaction temperature to about 45 °C. In any of the embodiments herein, protecting the nitrogen of a compound of Formula B, or a salt thereof, comprises elevating reaction temperature to about 20 °C to 30 °C. In any of the embodiments herein,Attorney Docket No.: TGO-027WO protecting the nitrogen of a compound of Formula B, or a salt thereof, comprises elevating reaction temperature to about 25 °C to about 30 °C.

[0244] In any of the embodiments herein, the compound depicted by Formula C, or a saltthereof, is produced as a mixture comprising more than about 80% by weight or by mole fraction, more than about 85% by weight or by mole fraction, more than about 90% by weight or by mole fraction, more than about 91% by weight or by mole fraction, more than about 92% by weight or by mole fraction, more than about 93% by weight or by mole fraction, more than about 94% by weight or by mole fraction, more than about 95% by weight or by mole fraction, more than about 96% by weight or by mole fraction, more than about 97% by weight or by mole fraction, more than about 98% by weight or by mole fraction, more than about 98.5% by weight or by mole fraction, more than about 99% by weight or by mole fraction, more than about 99.1% by weight or by mole fraction, more than about 99.2% by weight or by mole fraction, more than about 99.3% by weight or by mole fraction, more than about 99.4% by weight or by mole fraction, more than about 99.5% by weight or by mole fraction, more than about 99.6% by weight or by mole fraction, more than about 99.7% by weight or by mole fraction, more than about 99.8% by weight or by mole fraction, more than about 99.9% by weight or by mole fraction, of the enantiomer:, or a salt thereof, compared to the enantiomer:, or a salt thereof. Asymmetric Hydrogenation

[0245] In any of the embodiments herein, a compound of Formula B, or a salt thereof, is beprepared by hydrogenating a compound of Formula A1:Formula A1, or a salt thereof, wherein R1is a chiral auxiliary,Attorney Docket No.: TGO-027WO thereby producing a compound of Formula B:Formula B, or a salt thereof.

[0246] In any of the embodiments herein, hydrogenating a compound of Formula A1, or a saltthereof, comprises contacting the compound of Formula A1, or a salt thereof, with a first catalyst.

[0247] In any of the embodiments herein, hydrogenating the compound of Formula A1, or asalt thereof, comprises contacting the compound of Formula A1 with less than about 10 mol% of a first catalyst. In any of the embodiments herein, hydrogenating the compound of Formula A1, or a salt thereof, comprises contacting the compound of Formula A1 with less than about 5 mol% of a first catalyst. In any of the embodiments herein, hydrogenating the compound of Formula A1, or a salt thereof, comprises contacting the compound of Formula A1 with less than about 4 mol% of a first catalyst. In any of the embodiments herein, hydrogenating the compound of Formula A1, or a salt thereof, comprises contacting the compound of Formula A1 with less than about 3 mol% of a first catalyst. In any of the embodiments herein, hydrogenating the compound of Formula A1, or a salt thereof, comprises contacting the compound of Formula A1, or a salt thereof, with less than about 2 mol% of a first catalyst. In any of the embodiments herein, hydrogenating the compound of Formula A1, or a salt thereof, comprises contacting the compound of Formula A1, or a salt thereof, with less than about 1.75 mol% of a first catalyst.

[0248] In any of the embodiments herein, hydrogenating the compound of Formula A1, or asalt thereof, comprises contacting the compound of Formula A1, or a salt thereof, with about 1 mol% to about 2 mol% of a first catalyst. In any of the embodiments herein, hydrogenating the compound of Formula A1, or a salt thereof, comprises contacting the compound of Formula A1, or a salt thereof, with about 1.5 mol% to about 2 mol% of a first catalyst.

[0249] In any of the embodiments herein, hydrogenating the compound of Formula A1, or asalt thereof, comprises contacting the compound of Formula A1, or a salt thereof, with about 1.7 mol% of a first catalyst.

[0250] In any of the embodiments herein, the first catalyst is a palladium catalyst. In any of theembodiments herein, the first catalyst is a palladium (0) catalyst. In any of the embodiments herein, the first catalyst is palladium on carbon. In any of the embodiments herein, the firstAttorney Docket No.: TGO-027WO catalyst is about 5% by weight palladium on carbon. In any of the embodiments herein, the first catalyst is about 10% by weight palladium on carbon.

[0251] In any of the embodiments herein, the compound depicted by Formula B, or a saltthereof, is produced as a mixture comprising more than about 80% by weight or by mole fraction, more than about 85% by weight or by mole fraction, more than about 90% by weight or by mole fraction, more than about 91% by weight or by mole fraction, more than about 92% by weight or by mole fraction, more than about 93% by weight or by mole fraction, more than about 94% by weight or by mole fraction, more than about 95% by weight or by mole fraction, more than about 96% by weight or by mole fraction, more than about 97% by weight or by mole fraction, more than about 98% by weight or by mole fraction, more than about 98.5% by weight or by mole fraction, more than about 99% by weight or by mole fraction, more than about 99.1% by weight or by mole fraction, more than about 99.2% by weight or by mole fraction, more than about 99.3% by weight or by mole fraction, more than about 99.4% by weight or by mole fraction, more than about 99.5% by weight or by mole fraction, more than about 99.6% by weight or by mole fraction, more than about 99.7% by weight or by mole fraction, more than about 99.8% by weight or by mole fraction, more than about 99.9% by weight or by mole fraction, of the enantiomer:, or a salt thereof, compared to the enantiomer:, or a salt thereof. Flow

[0252] In any of the embodiments herein, hydrogenating a compound of Formula A1, or a saltthereof, to produce a compound of Formula B, or a salt thereof, comprises the use of a flow system. Applicants have found, surprisingly and advantageously, that flow hydrogenation allows for a lower catalyst loading as compared to results published in Angew. Chem. Int. Ed., 2021, 60, 6425-6429, which is incorporated by reference. In some embodiments, the flow system is a continuous flow system.Attorney Docket No.: TGO-027WO

[0253] In any of the embodiments herein, the flow system comprises the use of a micropacked bed reactor. In any of the embodiments herein, hydrogenating the compound of Formula A1, or a salt thereof, is performed under flow hydrogenation conditions. In any of the embodiments herein, hydrogenating a compound of Formula A1, or a salt thereof, is performed under continuous flow hydrogenation conditions. In some embodiments, the flow system comprises the use of a micropacked bed reactor and hydrogenating a compound of Formula A1, or a salt thereof, to form a compound of Formula B, or a salt thereof, is performed under flow hydrogenation conditions.

[0254] In any of the embodiments herein, hydrogenating a compound of Formula A1, or a salt thereof, comprises contacting the compound of Formula A1, or the salt thereof, with hydrogen gas at a pressure of at least about 1.0 megapascal (MPa). In any of the embodiments herein, hydrogenating a compound of Formula A1, or a salt thereof, comprises contacting the compound of Formula A1, or the salt thereof, with hydrogen gas at a pressure of at least about 2.0 megapascal (MPa). In any of the embodiments herein, hydrogenating a compound of Formula A1, or a salt thereof, comprises contacting the compound of Formula A1, or the salt thereof, with hydrogen gas at a pressure of at least about 2.5 megapascal (MPa). In any of the embodiments herein, hydrogenating a compound of Formula A1, or the salt thereof, comprises contacting the compound of Formula A1, the salt thereof, with hydrogen gas at a pressure of between about 2.0 megapascal (MPa) and 3.0 megapascal (MPa). In any of the embodiments herein, hydrogenating a compound of Formula A1, or a salt thereof, comprises contacting the compound of Formula A1, the salt thereof, with hydrogen gas at a pressure of about 2.5 megapascal (MPa). Batch

[0255] In any of the embodiments herein, hydrogenating a compound of Formula A1, or a salt thereof, to produce the compound of Formula B, or a salt thereof, comprises the use of a batch system. In some embodiments, the batch system comprises the use of a parr hydrogenator.

[0256] In any of the embodiments herein, hydrogenating a compound of Formula A1, or a salt thereof, comprises contacting the compound of Formula A1, or the salt thereof, with hydrogen gas. In any of the embodiments herein, hydrogenating a compound of Formula A1, or a salt thereof, comprises contacting the compound of Formula A1, or the salt thereof, with hydrogen gas. In any of the embodiments herein, hydrogenating a compound of Formula A1, or a salt thereof, comprises contacting the compound of Formula A1, or the salt thereof, with hydrogen gas at a pressure of at least about 1.0 megapascal (MPa). In any of the embodiments herein,Attorney Docket No.: TGO-027WO hydrogenating a compound of Formula A1, or a salt thereof, comprises contacting the compound of Formula A1, or the salt thereof, with hydrogen gas at a pressure of at least about 2.0 megapascal (MPa). In any of the embodiments herein, hydrogenating a compound of Formula A1, or a salt thereof, comprises contacting the compound of Formula A1, or the salt thereof, with hydrogen gas at a pressure of at least about 2.5 megapascal (MPa). In any of the embodiments herein, hydrogenating a compound of Formula A1, or a salt thereof, comprises contacting the compound of Formula A1, or the salt thereof, with hydrogen gas at a pressure of between about 2.0 megapascal (MPa) and 3.0 megapascal (MPa). In any of the embodiments herein, hydrogenating a compound of Formula A1, or a salt thereof, comprises contacting the compound of Formula A1, or the salt thereof, with hydrogen gas at a pressure of about 2.5 megapascal (MPa).

[0257] In any of the embodiments herein, hydrogenating a compound of Formula A1, or a salt thereof, is conducted at a reaction temperature of from about 55 °C to about 75 °C; alternatively, the reaction temperature is about 60 °C to about 70 °C; alternatively, the reaction temperature is about 65 °C.

[0258] In any of the embodiments herein, hydrogenating a compound of Formula A1, or a salt thereof, is conducted in the presence of a second acid. In any of the embodiments herein, the second acid is an inorganic acid. In any of the embodiments herein, the second acid is sulfuric acid. In any of the embodiments herein, the second acid is an organic acid. In any of the embodiments herein, the second acid is an organosulfuric acid. In any of the embodiments herein, the second acid is methanesulfonic acid (MSA).

[0259] In any of the embodiments herein, hydrogenating a compound of Formula A1, or a salt thereof, is conducted in the presence of a first solvent. In any of the embodiments herein, the first solvent is a polar solvent. In any of the embodiments herein, the first solvent is tetrahydrofuran (THF).

[0260] In any of the embodiments herein, hydrogenating a compound of Formula A1, or a salt thereof, is conducted in the presence of a second solvent. In any of the embodiments herein, the second solvent is water.

[0261] In any of the embodiments herein, hydrogenating a compound of Formula A1, or a salt thereof, gives the compound of Formula B as a solid. Asymmetric Amidation

[0262] In some embodiments, provided herein is a process for preparing a compound of Formula B:Attorney Docket No.: TGO-027WOFormula B, or a salt thereof, comprising: enzymatically amidating a compound of Formula A2:Formula A2, or a salt thereof, wherein R11is C1-C6alkyl, thereby producing a compound of Formula B:Formula B, or a salt thereof.

[0263] In some embodiments, provided herein is a process for preparing the compound ofFormula X:Formula X, or a salt thereof, comprising: enzymatically amidating a compound of Formula A2:Formula A2, or a salt thereof, wherein R11is C1-C6alkyl, thereby producing a compound of Formula B:Formula B, or a salt thereof; andAttorney Docket No.: TGO-027WO converting the compound of Formula B, or a salt thereof, to the compound of Formula X.

[0264] In some embodiments, the process further comprises enzymatically amidating acompound of Formula A2:Formula A2, or a salt thereof, thereby producing a compound of Formula B:Formula B, or a salt thereof; and converting the compound of Formula B, or a salt thereof, to a compound of FormulaC, Formula E, Formula F, or Formula G, or a salt thereof, or a first salt of a compound ofFormula I, a second salt of a compound of Formula I, or the compound of Formula X.

[0265] In any of the embodiments herein, a compound of Formula B, or a salt thereof, isprepared by enzymatically amidating a compound of Formula A2:Formula A2, or a salt thereof, wherein R11is C1-C6 alkyl, thereby producing a compound of Formula B:Formula B, or a salt thereof.

[0266] In any of the embodiments herein, enzymatically amidating a compound of FormulaA2 comprises contacting the compound of Formula A2 with a first enzyme.

[0267] In any of the embodiments herein, enzymatically amidating a compound of FormulaA2 comprises contacting the compound of Formula A2 with about 1% to about 5% by weight of the first enzyme. In any of the embodiments herein, enzymatically amidating a compound of Formula A2 comprises contacting the compound of Formula A2 with about 1% to about 3% by weight of the first enzyme. In any of the embodiments herein, enzymatically amidating a compound of Formula A2 comprises contacting the compound of Formula A2 with aboutAttorney Docket No.: TGO-027WO 1.5% to about 2.5% by weight of the first enzyme. In any of the embodiments herein, enzymatically amidating a compound of Formula A2 comprises contacting the compound of Formula A2 with about 2% by weight of the first enzyme.

[0268] In any of the embodiments herein, the first enzyme is pyridoxal phosphate. In any ofthe embodiments herein, the first enzyme is an enzyme capable of catalyzing the enzymatic amidation of a compound of Formula A2 to a compound of Formula B.

[0269] In any of the embodiments herein, enzymatically amidating a compound of FormulaA2 comprises contacting the compound of Formula A2 with a second enzyme.

[0270] In any of the embodiments herein, enzymatically amidating a compound of FormulaA2 comprises contacting the compound of Formula A2 with about 1% to about 5% by weight of the second enzyme. In any of the embodiments herein, enzymatically amidating a compound of Formula A2 comprises contacting the compound of Formula A2 with about 1% to about 3% by weight of the second enzyme. In any of the embodiments herein, enzymatically amidating a compound of Formula A2 comprises contacting the compound of Formula A2 with about 1.5% to about 2.5% by weight of the second enzyme. In any of the embodiments herein, enzymatically amidating a compound of Formula A2 comprises contacting the compound of Formula A2 with about 2% by weight of the second enzyme.

[0271] In any of the embodiments herein, the second enzyme is an amine transaminase. In anyof the embodiments herein, the second enzyme is a naturally occurring (wild-type) amine transaminase. In any of the embodiments herein, the second enzyme is an engineered amine transaminase capable of catalyzing the enzymatic amidation of a compound of Formula A2 to a compound of Formula B. In any of the embodiments herein, the second enzyme is ATA- 22403. Pivalamide protection

[0272] In any of the embodiments herein, a compound of Formula K, or a salt thereof, isprepared by pivalamide protecting a compound of Formula J:Formula J, thereby producing a compound of Formula K:Formula K, or a salt thereof.Attorney Docket No.: TGO-027WO

[0273] In any of the embodiments herein, pivalamide protecting a compound of Formula J,or a salt thereof, comprises contacting the compound of Formula J, or a salt thereof, with pivaloyl chloride (trimethylacetyl chloride). In any of the embodiments herein, pivalamide protecting a compound of Formula J, or a salt thereof, comprises contacting the compound of Formula J, or a salt thereof, with a seventh base. In any of the embodiments herein, the seventh base is an inorganic base. In any of the embodiments herein, the seventh base is an organic base. In any of the embodiments herein, the seventh base is an amine base (e.g., triethylamine (TEA), diisopropylethylamine (DIPEA), 4-dimethylamino pyridine (DMAP). In any of the embodiments herein, the seventh base is triethylamine (TEA). In any of the embodiments herein, pivalamide protecting a compound of Formula J, or a salt thereof, comprises lowering the reaction temperature to between about -10 °C and about 10 °C. In any of the embodiments herein, pivalamide protecting a compound of Formula J, or a salt thereof, comprises lowering the reaction temperature to about 0 °C. Acetyl installation

[0274] In any of the embodiments herein, a compound of Formula L, or a salt thereof, isprepared by installing an acetyl group on a compound of Formula K:Formula K, thereby producing a compound of Formula L:Formula L, or a salt thereof.

[0275] In any of the embodiments herein, converting the compound of Formula K, or a saltthereof, to a compound of Formula L, or a salt thereof, comprises contacting the compound of Formula K, or a salt thereof with a fourteenth solvent. In any of the embodiments herein, the fourteenth solvent is an organic solvent. In any of the embodiments herein, the fourteenth solvent is a polar solvent. In any of the embodiments herein, the fourteenth solvent is tetrahydrofuran (THF). In any of the embodiments herein, converting the compound ofFormula K, or a salt thereof, to a compound of Formula L, or a salt thereof, comprisesAttorney Docket No.: TGO-027WOcontacting the compound of Formula K, or a salt thereof, with an eighth base. In any of theembodiments herein, the eighth base is an inorganic base. In any of the embodiments herein, the eighth base is an organic base. In any of the embodiments herein, the eighth base is an amine base. In any of the embodiments herein, the eighth base is a lithium base. In any of the embodiments herein, the eighth base is n-butyllithium. In any of the embodiments therein, contacting the compound of Formula K with the eighth base comprises lowering reaction temperature to below 0° C. In any of the embodiments therein, contacting the compound of Formula K with the eighth base comprises lowering reaction temperature to between about - 10 ºC to about 0 °C. In any of the embodiments therein, contacting the compound of Formula K with the eighth base comprises lowering reaction temperature to about -5 ºC.

[0276] In any of the embodiments herein, converting the compound of Formula K, or a saltthereof, to a compound of Formula L, or a salt thereof, comprises contacting the compound of Formula K, or a salt thereof with N-Methoxy-N-methylacetamide.

[0277] In any of the embodiments herein, contacting the compound of Formula K, or a saltthereof with N-Methoxy-N-methylacetamide comprises lowering reaction temperature to below about -40 ºC. In any of the embodiments herein, contacting the compound of Formula K, or a salt thereof with N-Methoxy-N-methylacetamide comprises lowering reaction temperature to between about -60 ºC to about -40 °C. In any of the embodiments herein, contacting the compound of Formula K, or a salt thereof with N-Methoxy-N-methylacetamide comprises lowering reaction temperature to about -50 ºC.

[0278] In any of the embodiments herein, converting the compound of Formula K, or a saltthereof, to a compound of Formula L, or a salt thereof is performed in a continuous stirred tank reactor or a series of continuous stirred tank reactors. Carbonyl reduction and pivalamide deprotection

[0279] In any of the embodiments herein, a compound of Formula M, or a salt thereof, isprepared by reducing the carbonyl group and deprotecting the pivalamide of a compound of Formula L:Formula L, thereby producing a compound of Formula M:Attorney Docket No.: TGO-027WOFormula M, or a salt thereof.

[0280] In any of the embodiments herein, reducing the carbonyl group and deprotecting thepivalamide of a compound of Formula L or a salt thereof, comprises contacting the compound of Formula L with hydrazine hydrate. In any of the embodiments herein, reducing the carbonyl group and deprotecting the pivalamide of a compound of Formula L or a salt thereof, comprises contacting the compound of Formula L with a ninth base. In any of the embodiments herein, the ninth base is an inorganic base. In any of the embodiments herein, the ninth base is a hydroxide base. In any of the embodiments herein, the ninth base is LiOH, NaOH, KOH, or CsOH. In any of the embodiments herein, the ninth base is KOH. In any of the embodiments herein, reducing the carbonyl group and deprotecting the pivalamide of a compound of Formula L or a salt thereof, comprises contacting the compound of Formula L with a fifteenth solvent. In any of the embodiments herein, the fifteenth solvent is an organic solvent. In any of the embodiments herein, the fifteenth solvent is a polar solvent. In any of the embodiments herein, the fifteenth solvent is a high-boiling point solvent. In any of the embodiments herein, the fifteenth solvent is triethylene glycol. In any of the embodiments herein, reducing the carbonyl group and deprotecting the pivalamide of a compound of Formula L or a salt thereof, comprises elevating reaction temperature to higher than 180 °C. In any of the embodiments herein, reducing the carbonyl group and deprotecting the pivalamide of a compound of Formula L or a salt thereof, comprises elevating reaction temperature to between about 180 °C to about 220 °C. In any of the embodiments herein, reducing the carbonyl group and deprotecting the pivalamide of a compound of Formula L or a salt thereof, comprises elevating reaction temperature to between about 190 °C to about 210 °C. In any of the embodiments herein, reducing the carbonyl group and deprotecting the pivalamide of a compound of Formula L or a salt thereof, comprises elevating reaction temperature to about 200 °C. In any of the embodiments herein, reducing the carbonyl group and deprotecting the pivalamide of a compound of Formula L or a salt thereof is performed in a plug flow reactor (PFR). Nitration

[0281] In any of the embodiments herein, a compound of Formula N, or a salt thereof, isprepared by nitration of a compound of Formula M:Attorney Docket No.: TGO-027WOFormula M, thereby producing a compound of Formula N:Formula N, or a salt thereof.

[0282] In any of the embodiments herein, nitration of a compound of Formula M, or a salt thereof, comprises contacting the compound of Formula M with a mixture of sulfuric acid (H2SO4) and nitric acid (HNO3). In any of the embodiments herein, nitration of a compound of Formula M, or a salt thereof, is performed in a plug flow reactor (PFR). Nitrogen protection

[0283] In any of the embodiments herein, a compound of Formula O, or a salt thereof, is prepared by nitrogen protection of a compound of Formula N:Formula N, thereby producing a compound of Formula O:Formula O, or a salt thereof wherein R6and R7are each an independently selected nitrogen protecting group.

[0284] In any of the embodiments herein, nitrogen protection of a compound of Formula N, or a salt thereof, comprises contacting the compound of Formula N with a second nitrogen protecting group reagent. In any of the embodiments herein, the second nitrogen protecting group reagent comprises a carbamate. In any of the embodiments herein, the second nitrogen protecting group reagent comprises . In any of the embodiments herein, the secondnitrogen protecting group reagent is . In any of the embodiments herein,nitrogen protection of a compound of Formula N, or a salt thereof, comprises contacting the compound of Formula N with an eighth base. In any of the embodiments herein, the eighth base is an inorganic base. In any of the embodiments herein, the eighth base is an organic base.Attorney Docket No.: TGO-027WO In any of the embodiments herein, the eighth base is an amine base (e.g., triethylamine (TEA), diisopropylethylamine (DIPEA), 4-dimethylamino pyridine (DMAP). In any of the embodiments herein, the eighth base is dimethylamino pyridine (DMAP). In any of the embodiments herein, nitrogen protection of a compound of Formula N, or a salt thereof, comprises contacting the compound of Formula N with a sixteenth solvent. In any of the embodiments herein, the sixteenth solvent is an organic solvent. In any of the embodiments herein, the sixteenth solvent is a polar solvent. In any of the embodiments herein, the sixteenth solvent is tetrahydrofuran (THF). In any of the embodiments herein, nitrogen protection of a compound of Formula N, or a salt thereof, comprises lowering the reaction temperature to below about 20 °C. In any of the embodiments herein, nitrogen protection of a compound of Formula N, or a salt thereof, comprises lowering the reaction temperature to between about 8 °C and about 18 °C. In any of the embodiments herein, nitrogen protection of a compound of Formula N, or a salt thereof, comprises lowering the reaction temperature to about 13 °C. Nitro reduction

[0285] In any of the embodiments herein, a compound of Formula P, or a salt thereof, isprepared by nitro reduction of a compound of Formula O:Formula O, thereby producing a compound of Formula P:Formula P, or a salt thereof wherein R6and R7are each an independently selected nitrogen protecting group.

[0286] In any of the embodiments herein, nitro reduction of a compound of Formula P, or asalt thereof, comprises In any of the embodiments herein, hydrogenating a compound of Formula P, or a salt thereof, comprises contacting the compound of Formula P, or a salt thereof, with a third catalyst.

[0287] In any of the embodiments herein, hydrogenating the compound of Formula P, or asalt thereof, comprises contacting the compound of Formula P with less than about 40 % w / w of a third catalyst. In any of the embodiments herein, hydrogenating the compound of FormulaAttorney Docket No.: TGO-027WO P, or a salt thereof, comprises contacting the compound of Formula P with less than about 30 % w / w of a third catalyst.

[0288] In any of the embodiments herein, hydrogenating the compound of Formula P, or a salt thereof, comprises contacting the compound of Formula P, or a salt thereof, with about 10 % w / w to about 40 % w / w of a third catalyst. In any of the embodiments herein, hydrogenating the compound of Formula P, or a salt thereof, comprises contacting the compound of Formula P, or a salt thereof, with about 20 % w / w to about 35 % w / w of a third catalyst.

[0289] In any of the embodiments herein, hydrogenating the compound of Formula P, or a salt thereof, comprises contacting the compound of Formula P, or a salt thereof, with about 30 % w / w of a third catalyst.

[0290] In any of the embodiments herein, the third catalyst is a nickel catalyst. In any of the embodiments herein, the third catalyst is a nickel (0) catalyst. In any of the embodiments herein, the third catalyst is nickel on carbon. In any of the embodiments herein, hydrogenating the compound of Formula P, or a salt thereof, comprises contacting the compound of Formula P, or a salt thereof, with hydrogen. In any of the embodiments herein, hydrogenating the compound of Formula P, or a salt thereof, comprises contacting the compound of Formula P, or a salt thereof, with hydrogen at a pressure of at least about 2 MPa (e.g., between about 2 MPa and about 3 MPa). In any of the embodiments herein, hydrogenating the compound of Formula P, or a salt thereof, comprises contacting the compound of Formula P, or a salt thereof, with hydrogen at a pressure of about 2.5 MPa.

[0291] In any of the embodiments herein, hydrogenating the compound of Formula P, or a salt thereof, comprises contacting the compound of Formula P, or a salt thereof, with a seventeenth solvent. In any of the embodiments herein, the seventeenth solvent is a protic solvent. In any of the embodiments herein, the seventeenth solvent is an alcohol. In any of the embodiments herein, the seventeenth solvent is methanol (MeOH). In any of the embodiments herein, hydrogenating the compound of Formula P, or a salt thereof, comprises elevating reaction temperature to higher than 40 °C. In any of the embodiments herein, hydrogenating the compound of Formula P, or a salt thereof, comprises elevating reaction temperature to about 40 °C to about 60 °C. In any of the embodiments herein, hydrogenating the compound of Formula P, or a salt thereof, comprises elevating reaction temperature to about 50 °C. Oxalylamide installationAttorney Docket No.: TGO-027WO

[0292] In any of the embodiments herein, a compound of Formula R, or a salt thereof, isprepared by oxalylamide installation on a compound of Formula P:Formula P, thereby producing a compound of Formula R:Formula R, or a salt thereof R6and R7are each an independently selected nitrogen protecting group and R12is C1-C6alkyl.

[0293] In any of the embodiments herein, oxalylamide installation on a compound of FormulaP, or a salt thereof, comprises contacting the compound of Formula P with wherein R12is C1-C6alkyl. In any of the embodiments herein, oxalylamide installation on a compound of Formula P, or a salt thereof, comprises contacting the compound of Formula Pwith .In any of the embodiments herein, oxalylamide installation on a compound of Formula P, or a salt thereof, comprises contacting the compound of Formula P with a tenth base. In any of the embodiments herein, the tenth base is an inorganic base. In any of the embodiments herein, the tenth base is an inorganic base. In any of the embodiments herein, the tenth base is an organic base. In any of the embodiments herein, the tenth base is an amine base (e.g., triethylamine (TEA), diisopropylethylamine (DIPEA), 4-dimethylamino pyridine (DMAP). In any of the embodiments herein, the tenth base is triethylamine (TEA). In any of the embodiments herein, oxalylamide installation on a compound of Formula P, or a salt thereof, comprises contacting the compound of Formula P with an eighteenth solvent. In any of the embodiments herein, the eighteenth solvent is an organic solvent. In any of the embodiments herein, the eighteenth solvent is a polar solvent. In any of the embodiments herein, the nineteenth solvent is ethyl acetate (EtOAc).

[0294] In any of the embodiments herein, oxalylamide installation on a compound of FormulaP, or a salt thereof comprises lowering the reaction temperature to between about 0 °C andAttorney Docket No.: TGO-027WO about 10 °C. In any of the embodiments herein, oxalylamide installation on a compound of Formula P, or a salt thereof, comprises lowering the reaction temperature to about 5 °C. Saponification

[0295] In any of the embodiments herein, a compound of Formula H, or a salt thereof, isprepared by saponification of a compound of Formula R:Formula R, thereby producing a compound of Formula H:Formula H, or a salt thereof R6and R7are each an independently selected nitrogen protecting group and R12is C1-C6alkyl.

[0296] In any of the embodiments herein, saponification of a compound of Formula R, or asalt thereof, comprises contacting the compound of Formula R with an eleventh base. In any of the embodiments herein, the eleventh base is an inorganic base. In any of the embodiments herein, the ninth base is a hydroxide base. In any of the embodiments herein, the eleventh base is LiOH, NaOH, KOH, or CsOH. In any of the embodiments herein, the eleventh base is LiOH. In any of the embodiments herein, saponification of a compound of Formula R, or a salt thereof, comprises contacting the compound of Formula R with a nineteenth solvent. In any of the embodiments herein, the nineteenth solvent is a protic solvent. In any of the embodiments herein, the nineteenth solvent is an alcohol. In any of the embodiments herein, the nineteenth solvent is ethanol (EtOH).

[0297] In any of the embodiments herein, saponification of a compound of Formula R, or asalt thereof comprises lowering the reaction temperature to between about -10 °C and about 10 °C. In any of the embodiments herein, saponification of a compound of Formula R, or a salt thereof, comprises lowering the reaction temperature to about 0 °C. SELECTED EMBODIMENTS Embodiment 1. A process for preparing a compound of Formula X:Attorney Docket No.: TGO-027WOFormula X, or a salt thereof, comprising: enzymatically amidating a compound of Formula A2:Formula A2, or a salt thereof, wherein R11is C1-C6 alkyl, thereby producing a compound of Formula B:Formula B, or a salt thereof; and converting the compound of Formula B, or a salt thereof, to the compound of Formula X. Embodiment 2. The process of embodiment 1, wherein the process further comprises protecting the nitrogen of a compound of Formula B:Formula B, or a salt thereof, thereby producing a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group; and converting the compound of Formula C, or a salt thereof, to the compound of Formula X.Attorney Docket No.: TGO-027WO Embodiment 3. The process of embodiment 1 or 2, wherein the process further comprises cross-coupling a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group, with a compound of Formula D:Formula D, or a salt thereof, wherein R3is a boronic acid or a boronic ester, thereby producing a compound of Formula E:Formula E, or a salt thereof, wherein R2is a nitrogen protecting group; and converting the compound of Formula E, or a salt thereof, to the compound of Formula X. Embodiment 4. The process of any one of embodiments 1 to 3, wherein the process further comprises removing nitrogen protecting group from a compound of Formula E:Formula E, or a salt thereof, wherein R2is a nitrogen protecting group, thereby producing a compound of Formula F:Attorney Docket No.: TGO-027WOor a salt thereof; and converting the compound of Formula F, or a salt thereof, to the compound of Formula X. Embodiment 5. The process of any one of embodiments 1 to 4, wherein the process further comprises reducing a compound of Formula F:Formula F, or a salt thereof, thereby producing a compound of Formula G:Formula G,or a salt thereof; and converting the compound of Formula G, or a salt thereof, to the compound of Formula X. Embodiment 6. The process of any one of embodiments 1 to 4, wherein the process further comprises enzymatically reducing a compound of Formula F:Attorney Docket No.: TGO-027WOor a salt thereof, thereby producing a compound of Formula G:Formula G,or a salt thereof; and converting the compound of Formula G, or a salt thereof, to the compound of Formula X. Embodiment 7. The process of any one of embodiments 1 to 6, wherein the process further comprises coupling a compound of Formula G:Formula G,or a salt thereof, with a compound of Formula H:Formula H, or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group,Attorney Docket No.: TGO-027WO thereby producing a first salt of a compound of Formula I:wherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group; and converting the first salt of the compound of Formula I to the compound of Formula X. Embodiment 8. The process of any one of embodiments 1 to 7, wherein the process further comprises removing one or more nitrogen protecting groups from a first salt of a compound of Formula I:wherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group, thereby producing a second salt of a compound of Formula I:Attorney Docket No.: TGO-027WO wherein eachconverting the second salt of the compound of Formula I to the compound of Formula X. Embodiment 9. The process of any one of embodiments 1 to 8, wherein the process further comprises free-basing a second salt of a compound of Formula I:wherein each of R8and R9is H, thereby producing the compound of Formula X. Embodiment 10. A process for preparing a compound of Formula X:Attorney Docket No.: TGO-027WO comprising: reducing a compound of Formula F:or a salt thereof, thereby producing a compound of Formula G:Formula G,or a salt thereof; and converting the compound of Formula G, or a salt thereof, to the compound of Formula X. Embodiment 11. A process for preparing a compound of Formula X:Formula X, or a salt thereof, comprising: enzymatically reducing a compound of Formula F:Attorney Docket No.: TGO-027WOFormula F, or a salt thereof, thereby producing a compound of Formula G:Formula G,or a salt thereof; and converting the compound of Formula G, or a salt thereof, to the compound of Formula X. Embodiment 12. The process of embodiment 10 or 11, wherein the process further comprises coupling a compound of Formula G:Formula G,or a salt thereof, with a compound of Formula H:Formula H, or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group,Attorney Docket No.: TGO-027WO thereby producing a first salt of a compound of Formula I:wherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group; and converting the first salt of the compound of Formula I to the compound of Formula X. Embodiment 13. The process of any one of embodiments 10 to 12, wherein the process further comprises removing one or more nitrogen protecting groups from a first salt of a compound of Formula I:wherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group, thereby producing a second salt of a compound of Formula I:Attorney Docket No.: TGO-027WO wherein eachconverting the second salt of the compound of Formula I to the compound of Formula X. Embodiment 14. The process of any one of embodiments 10 to 13, wherein the process further comprises free-basing a second salt of a compound of Formula I:wherein each of R8and R9is H, thereby producing the compound of Formula X. Embodiment 15. The process of any one of embodiments 10 to 14, wherein the process further comprises hydrogenating a compound of Formula A1:Formula A1, or a salt thereof, wherein R1is a chiral auxiliary, thereby producing a compound of Formula B:Formula B, or a salt thereof; andAttorney Docket No.: TGO-027WO converting the compound of Formula B, or a salt thereof, to the compound of Formula F, or a salt thereof. Embodiment 16. The process of any one of embodiments 10 to 14, wherein the process further comprises enzymatically amidating a compound of Formula A2:Formula A2, or a salt thereof, wherein R11is C1-C6 alkyl, thereby producing a compound of Formula B:Formula B, or a salt thereof; and converting the compound of Formula B, or a salt thereof, to the compound of Formula F, or a salt thereof. Embodiment 17. The process of any one of embodiments 10 to 16, wherein the process further comprises protecting the nitrogen of a compound of Formula B:Formula B, or a salt thereof, thereby producing a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group; and converting the compound of Formula C, or a salt thereof, to the compound of Formula F, or a salt thereof. Embodiment 18. The process of any one of embodiments 10 to 17, wherein the process further comprises cross-coupling a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group,Attorney Docket No.: TGO-027WO with a compound of Formula D:or a salt thereof, wherein R3is a boronic acid or a boronic ester, thereby producing a compound of Formula E:Formula E, or a salt thereof, wherein R2is a nitrogen protecting group; and converting the compound of Formula E, or a salt thereof, to the compound of Formula F, or a salt thereof. Embodiment 19. The process of any one of embodiments 10 to 17, wherein the process further comprises removing nitrogen protecting group from a compound of Formula E:or a salt thereof, wherein R2is a nitrogen protecting group, thereby producing a compound of Formula F:Formula F, or a salt thereof. Embodiment 20. A process for preparing a compound of Formula X:Attorney Docket No.: TGO-027WOFormula X, comprising: coupling a compound of Formula G:Formula G,or a salt thereof, with a compound of Formula H:Formula H, or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, thereby producing a first salt of a compound of Formula I:Attorney Docket No.: TGO-027WOFormula I, or a salt thereof, wherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group; and converting the first salt of the compound of Formula I to the compound of Formula X. Embodiment 21. The process of embodiment 20, wherein the process further comprises removing one or more nitrogen protecting groups from a first salt of a compound of Formula I:Formula I, or a salt thereof, wherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group, thereby producing a second salt of a compound of Formula I:Attorney Docket No.: TGO-027WO wherein eachconverting the second salt of the compound of Formula I to the compound ofFormula X. Embodiment 22. The process of embodiment 20 or 21, wherein the process further comprises free-basing a second salt of a compound of Formula I:wherein each of R8and R9is H, thereby producing the compound of Formula X. Embodiment 23. The process of any one of embodiments 20 to 22, wherein the process further comprises hydrogenating a compound of Formula A1:Formula A1, or a salt thereof, wherein R1is a chiral auxiliary, thereby producing a compound of Formula B:Formula B, or a salt thereof; andAttorney Docket No.: TGO-027WO converting the compound of Formula B, or a salt thereof, to the compound of Formula G, or a salt thereof. Embodiment 24. The process of any one of embodiments 20 to 22, wherein the process further comprises enzymatically amidating a compound of Formula A2:Formula A2, or a salt thereof, wherein R11is C1-C6 alkyl, thereby producing a compound of Formula B:Formula B, or a salt thereof; and converting the compound of Formula B, or a salt thereof, to the compound of Formula G, or a salt thereof. Embodiment 25. The process of any one of embodiments 20 to 24, wherein the process further comprises protecting the nitrogen of a compound of Formula B:Formula B, or a salt thereof, thereby producing a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group; and converting the compound of Formula C, or a salt thereof, to the compound of Formula G, or a salt thereof. Embodiment 26. The process of any one of embodiments 20 to 25, wherein the process further comprises cross-coupling a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group,Attorney Docket No.: TGO-027WO with a compound of Formula D:or a salt thereof, thereby producing a compound of Formula E:Formula E, or a salt thereof, wherein R2is a nitrogen protecting group; and converting the compound of Formula E, or a salt thereof, to the compound of Formula G, or a salt thereof. Embodiment 27. The process of any one of embodiments 20 to 26, wherein the process further comprises removing nitrogen protecting group from a compound of Formula E:or a salt thereof, wherein R2is a nitrogen protecting group, thereby producing a compound of Formula F:or a salt thereof; and converting the compound of Formula F, or a salt thereof, to the compound of Formula G, or a salt thereof.Attorney Docket No.: TGO-027WO Embodiment 28. The process of any one of embodiments 20 to 27, wherein the process further comprises reducing a compound of Formula F:or a salt thereof, thereby producing a compound of Formula G:or a salt thereof. Embodiment 29. The process of any one of embodiments 20 to 27, wherein the process further comprises enzymatically reducing a compound of Formula F:Formula F, or a salt thereof, thereby producing a compound of Formula G: Formula G,Attorney Docket No.: TGO-027WO or a salt thereof. Embodiment 30. A process for preparing a compound of Formula X:Formula X, comprising: free-basing a second salt of a compound of Formula I:Formula I, wherein each of R8and R9is H, thereby producing the compound of Formula X. Embodiment 31. The process embodiment 30, wherein the process further comprises hydrogenating a compound of Formula A1:Formula A1, or a salt thereof, wherein R1is a chiral auxiliary, thereby producing a compound of Formula B:Formula B, or a salt thereof; andAttorney Docket No.: TGO-027WO converting the compound of Formula B, or a salt thereof, to the second salt of the compound of Formula I. Embodiment 32. The process embodiment 30, wherein the process further comprises enzymatically amidating a compound of Formula A2:Formula A2, or a salt thereof, wherein R11is C1-C6 alkyl, thereby producing a compound of Formula B: Formula B, or a salt thereof; and converting the compound of Formula B, or a salt thereof, to the second salt of the compound of Formula I. Embodiment 33. The process of any one of embodiments 30 to 32, wherein the process further comprises protecting the nitrogen of a compound of Formula B:Formula B, or a salt thereof, thereby producing a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group; and converting the compound of Formula C, or a salt thereof, to the second salt of the compound of Formula I. Embodiment 34. The process of any one of embodiments 30 to 33, wherein the process further comprises cross-coupling a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group,Attorney Docket No.: TGO-027WO with a compound of Formula D:or a salt thereof, wherein R3is a boronic acid or a boronic ester, thereby producing a compound of Formula E:Formula E, or a salt thereof, wherein R2is a nitrogen protecting group; and converting the compound of Formula E, or a salt thereof, to the second salt of the compound of Formula I. Embodiment 35. The process of any one of embodiments 30 to 34, wherein the process further comprises removing nitrogen protecting group from a compound of Formula E:or a salt thereof, wherein R2is a nitrogen protecting group, thereby producing a compound of Formula F:or a salt thereof; and converting the compound of Formula F, or a salt thereof, to the second salt of the compound of Formula I.Attorney Docket No.: TGO-027WO Embodiment 36. The process of any one of embodiments 30 to 35, wherein the process further comprises reducing a compound of Formula F:or a salt thereof, thereby producing a compound of Formula G:or a salt thereof; and converting the compound of Formula G, or a salt thereof, to the second salt of the compound of Formula I. Embodiment 37. The process of any one of embodiments 30 to 35, wherein the process further comprises enzymatically reducing a compound of Formula F:Formula F, or a salt thereof, thereby producing a compound of Formula G:Attorney Docket No.: TGO-027WOFormula G,or a salt thereof; and converting the compound of Formula G, or a salt thereof, to the second salt of the compound of Formula I. Embodiment 38. The process of any one of embodiments 30 to 37, wherein the process further comprises coupling a compound of Formula G:Formula G,or a salt thereof, with a compound of Formula H:Formula H, or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, thereby producing a first salt of a compound of Formula I:Attorney Docket No.: TGO-027WOwherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group; and converting the first salt of the compound of Formula I to the second salt of the compound of Formula I. Embodiment 39. The process of any one of embodiments 30 to 38, wherein the process further comprises removing one or more nitrogen protecting groups from a first salt of a compound of Formula I:Formula I, wherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group, thereby producing a second salt of a compound of Formula I:Attorney Docket No.: TGO-027WO wherein eachEmbodiment 40. The process of any one of embodiments 1 to 39, wherein the process further comprises: pivalamide protecting a compound of Formula J:Formula J, or a salt thereof, thereby producing a compound of Formula K:Formula K, or a salt thereof; installing an acetyl group on a compound of Formula K:Formula K, or a salt thereof, thereby producing a compound of Formula L:Formula L, or a salt thereof; reducing the carbonyl and pivalamide deprotecting of a compound of Formula L:Attorney Docket No.: TGO-027WOFormula L, or a salt thereof, thereby producing a compound of Formula M:Formula M, or a salt thereof; nitrating a compound of Formula M:Formula M, or a salt thereof, thereby producing a compound of Formula N:Formula N, or a salt thereof; nitrogen protecting a compound of Formula N:Formula N, or a salt thereof, thereby producing a compound of Formula O:Formula O, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, nitro reducing a compound of Formula O:Attorney Docket No.: TGO-027WO or a salt thereof, thereby producing a compound of Formula P:Formula P, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, installing an oxalylamide on a compound of Formula P:Formula P, or a salt thereof, thereby producing a compound of Formula R:Formula R, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group and R12is C1-C6alkyl, saponifying a compound of Formula R:Formula R, or a salt thereof, thereby producing a compound of Formula H:Formula H, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group; andAttorney Docket No.: TGO-027WO converting the compound of Formula H, or a salt thereof, to the compound of Formula X. Embodiment 41. A process for preparing a compound of Formula X:Formula X, comprising: pivalamide protecting a compound of Formula J:Formula J, or a salt thereof, thereby producing a compound of Formula K:Formula K, or a salt thereof; installing an acetyl group on a compound of Formula K:Formula K, or a salt thereof, thereby producing a compound of Formula L:Formula L, or a salt thereof; reducing the carbonyl and pivalamide deprotecting of a compound of Formula L:Attorney Docket No.: TGO-027WOFormula L, or a salt thereof, thereby producing a compound of Formula M:Formula M, or a salt thereof; nitrating a compound of Formula M:Formula M, or a salt thereof, thereby producing a compound of Formula N:Formula N, or a salt thereof; nitrogen protecting a compound of Formula N:Formula N, or a salt thereof, thereby producing a compound of Formula O:Formula O, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, nitro reducing a compound of Formula O:Attorney Docket No.: TGO-027WO or a salt thereof, thereby producing a compound of Formula P:Formula P, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, installing an oxalylamide on a compound of Formula P:Formula P, or a salt thereof, thereby producing a compound of Formula R:Formula R, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group and R12is C1-C6alkyl, saponifying a compound of Formula RFormula R, or a salt thereof, thereby producing a compound of Formula H:Formula H, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group; andAttorney Docket No.: TGO-027WO converting the compound of Formula H, or a salt thereof, to the compound of Formula X. Embodiment 42. The process of embodiment 41, wherein the process further comprises: enzymatically amidating a compound of Formula A2:Formula A2, or a salt thereof, wherein R11is C1-C6alkyl, thereby producing a compound of Formula B:Formula B, or a salt thereof; and converting the compound of Formula B, or a salt thereof, to the compound of Formula X. Embodiment 43. The process of embodiment 41, wherein the process further comprises hydrogenating a compound of Formula A1:Formula A1, or a salt thereof, wherein R1is a chiral auxiliary, thereby producing a compound of Formula B:Formula B, or a salt thereof; and converting the compound of Formula B, or a salt thereof, to the compound of Formula X.. Embodiment 44. The process of any one of embodiments 41 to 43, wherein the process further comprises protecting the nitrogen of a compound of Formula B:Formula B,or a salt thereof, thereby producing a compound of Formula C:Formula C,Attorney Docket No.: TGO-027WO or a salt thereof, wherein R2is a nitrogen protecting group; and converting the compound of Formula C, or a salt thereof, to the compound of Formula X. Embodiment 45. The process of any one of embodiments 41 to 44, wherein the process further comprises cross-coupling a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group, with a compound of Formula D:Formula D, or a salt thereof, wherein R3is a boronic acid or a boronic ester, thereby producing a compound of Formula E:Formula E, or a salt thereof, wherein R2is a nitrogen protecting group; and converting the compound of Formula E, or a salt thereof, to the compound of Formula X. Embodiment 46. The process of any one of embodiments 41 to 45, wherein the process further comprises removing nitrogen protecting group from a compound of Formula E:Formula E, or a salt thereof, wherein R2is a nitrogen protecting group, thereby producing a compound of Formula F:Attorney Docket No.: TGO-027WOFormula F, or a salt thereof; and converting the compound of Formula F, or a salt thereof, to the compound of Formula X. Embodiment 47. The process of any one of embodiments 41 to 46, wherein the process further comprises reducing a compound of Formula F:Formula F, or a salt thereof, thereby producing a compound of Formula G:or a salt thereof; and converting the compound of Formula G, or a salt thereof, to the compound of Formula X. Embodiment 48. The process of any one of embodiments 41 to 46, wherein the process further comprises enzymatically reducing a compound of Formula F:Attorney Docket No.: TGO-027WOFormula F, or a salt thereof, thereby producing a compound of Formula G:Formula G,or a salt thereof; and converting the compound of Formula G, or a salt thereof, to the compound of Formula X. Embodiment 49. The process of any one of embodiments 41 to 48, wherein the process further comprises coupling a compound of Formula G:Formula G,or a salt thereof, with a compound of Formula H:Formula H, or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group,Attorney Docket No.: TGO-027WO thereby producing a first salt of a compound of Formula I:wherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group; and converting the first salt of the compound of Formula I to the compound of Formula X. Embodiment 50. The process of any one of embodiments 41 to 49, wherein the process further comprises removing one or more nitrogen protecting groups from a first salt of a compound of Formula I:wherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group, thereby producing a second salt of a compound of Formula I:Attorney Docket No.: TGO-027WO wherein eachconverting the second salt of the compound of Formula I to the compound of Formula X. Embodiment 51. The process of any one of embodiments 41 to 50, wherein the process further comprises free-basing a second salt of a compound of Formula I:wherein each of R8and R9is H, thereby producing the compound of Formula X. Embodiment 52. A process for preparing a compound of Formula X:Attorney Docket No.: TGO-027WOFormula X, or a salt thereof, comprising: hydrogenating a compound of Formula A1:Formula A1, or a salt thereof, wherein R1is a chiral auxiliary; thereby producing a compound of Formula B:Formula B, or a salt thereof; protecting the nitrogen of a compound of Formula B:Formula B, or a salt thereof, thereby producing a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group; cross-coupling a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group, with a compound of Formula D:Attorney Docket No.: TGO-027WOor a salt thereof, wherein R3is a boronic acid or a boronic ester, thereby producing a compound of Formula E:or a salt thereof, wherein R2is a nitrogen protecting group; removing nitrogen protecting group from a compound of Formula E:or a salt thereof, wherein R2is a nitrogen protecting group, thereby producing a compound of Formula F:Formula F, or a salt thereof; reducing a compound of Formula F:Attorney Docket No.: TGO-027WOor a salt thereof, thereby producing a compound of Formula G:Formula G, or a salt thereof; coupling a compound of Formula G:Formula G, or a salt thereof, with a compound of Formula H:or a salt thereof, thereby producing a first salt of a compound of Formula I:Attorney Docket No.: TGO-027WOwherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group; and removing one or more nitrogen protecting groups from a first salt of a compound of Formula I:Formula I, wherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group, thereby producing a second salt of a compound of Formula I:Formula I, wherein each of R8and R9is H; andAttorney Docket No.: TGO-027WO free-basing a second salt of a compound of Formula I:Embodiment 53. A process for preparing a compound of Formula X:Formula X, or a salt thereof, comprising: hydrogenating a compound of Formula A1:Formula A1,Attorney Docket No.: TGO-027WO or a salt thereof, thereby producing a compound of Formula B:Formula B, or a salt thereof; protecting the nitrogen of a compound of Formula B:Formula B, or a salt thereof, thereby producing a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group; cross-coupling a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group, with a compound of Formula D:Formula D, or a salt thereof, wherein R3is a boronic acid or a boronic ester, thereby producing a compound of Formula E:or a salt thereof, wherein R2is a nitrogen protecting group; removing nitrogen protecting group from a compound of Formula E:Attorney Docket No.: TGO-027WOor a salt thereof, wherein R2is a nitrogen protecting group, thereby producing a compound of Formula F:Formula F, or a salt thereof; enzymatically reducing a compound of Formula F:or a salt thereof, thereby producing a compound of Formula G:Formula G, or a salt thereof; coupling a compound of Formula G:Attorney Docket No.: TGO-027WOor a salt thereof, with a compound of Formula H:Formula H, or a salt thereof, thereby producing a first salt of a compound of Formula I:Formula I, wherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group; and removing one or more nitrogen protecting groups from a first salt of a compound of Formula I:Attorney Docket No.: TGO-027WOwherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group, thereby producing a second salt of a compound of Formula I:wherein each of R8and R9is H; and free-basing a second salt of a compound of Formula I:Formula I, wherein each of R8and R9is H, thereby producing the compound of Formula X:Attorney Docket No.: TGO-027WOFormula X. Embodiment 54. A process for preparing a compound of Formula X:or a salt thereof, comprising: enzymatically amidating a compound of Formula A2:Formula A2, or a salt thereof, wherein R11is C1-C6alkyl, thereby producing a compound of Formula B:Formula B, or a salt thereof; protecting the nitrogen of a compound of Formula B:Formula B, or a salt thereof, thereby producing a compound of Formula C:Attorney Docket No.: TGO-027WOFormula C, or a salt thereof, wherein R2is a nitrogen protecting group; cross-coupling a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group, with a compound of Formula D:Formula D, or a salt thereof, wherein R3is a boronic acid or a boronic ester, thereby producing a compound of Formula E:Formula E, or a salt thereof, wherein R2is a nitrogen protecting group; removing nitrogen protecting group from a compound of Formula E:Formula E, or a salt thereof, wherein R2is a nitrogen protecting group, thereby producing a compound of Formula F:Attorney Docket No.: TGO-027WOFormula F, or a salt thereof; reducing a compound of Formula F:Formula F, or a salt thereof, thereby producing a compound of Formula G:Formula G, or a salt thereof; coupling a compound of Formula G:Formula G, or a salt thereof, with a compound of Formula H:Attorney Docket No.: TGO-027WOFormula H, or a salt thereof, thereby producing a first salt of a compound of Formula I:wherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group; and removing one or more nitrogen protecting groups from a first salt of a compound of Formula I:wherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group, thereby producing a second salt of a compound of Formula I:Attorney Docket No.: TGO-027WO wherein eachfree-basing a second salt of a compound of Formula I:wherein each of R8and R9is H, thereby producing the compound of Formula X:Embodiment 55. A process for preparing a compound of Formula X:Attorney Docket No.: TGO-027WOFormula X, or a salt thereof, comprising: enzymatically amidating a compound of Formula A2:Formula A2, or a salt thereof, thereby producing a compound of Formula B:Formula B, or a salt thereof; protecting the nitrogen of a compound of Formula B:Formula B, or a salt thereof, thereby producing a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group; cross-coupling a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group,Attorney Docket No.: TGO-027WO with a compound of Formula D:or a salt thereof, wherein R3is a boronic acid or a boronic ester, thereby producing a compound of Formula E:Formula E, or a salt thereof, wherein R2is a nitrogen protecting group; removing nitrogen protecting group from a compound of Formula E:or a salt thereof, wherein R2is a nitrogen protecting group, thereby producing a compound of Formula F:or a salt thereof; enzymatically reducing a compound of Formula F:Attorney Docket No.: TGO-027WOor a salt thereof, thereby producing a compound of Formula G:Formula G, or a salt thereof; coupling a compound of Formula G:Formula G, or a salt thereof, with a compound of Formula H:or a salt thereof, thereby producing a first salt of a compound of Formula I:Attorney Docket No.: TGO-027WOwherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group; and removing one or more nitrogen protecting groups from a first salt of a compound of Formula I:Formula I, wherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group, thereby producing a second salt of a compound of Formula I:Formula I, wherein each of R8and R9is H; andAttorney Docket No.: TGO-027WO free-basing a second salt of a compound of Formula I:Formula I, wherein each of R8and R9is H, thereby producing the compound of Formula X:Formula X. Embodiment 56. A process for preparing a compound of Formula X:Formula X, comprising: hydrogenating a compound of Formula A1:Formula A1, or a salt thereof, wherein R1is a chiral auxiliary,Attorney Docket No.: TGO-027WO thereby producing a compound of Formula B:Formula B, or a salt thereof; protecting the nitrogen of a compound of Formula B:Formula B, or a salt thereof, thereby producing a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group; cross-coupling a compound of Formula C:Formula C, or a salt thereof, with a compound of Formula D:or a salt thereof, wherein R3is a boronic acid or a boronic ester, thereby producing a compound of Formula E:or a salt thereof; removing nitrogen protecting group from a compound of Formula E:Attorney Docket No.: TGO-027WOor a salt thereof, thereby producing a compound of Formula F:Formula F, or a salt thereof; reducing a compound of Formula F:Formula F, or a salt thereof, thereby producing a compound of Formula G:Formula G, or a salt thereof; pivalamide protecting a compound of Formula J:Attorney Docket No.: TGO-027WOFormula J, or a salt thereof, thereby producing a compound of Formula K:or a salt thereof; installing an acetyl group on a compound of Formula K:Formula K, or a salt thereof, thereby producing a compound of Formula L:Formula L, or a salt thereof; reducing the carbonyl and pivalamide deprotecting of a compound of Formula L:Formula L, or a salt thereof, thereby producing a compound of Formula M:Formula M, or a salt thereof; nitrating a compound of Formula M:Attorney Docket No.: TGO-027WOor a salt thereof, thereby producing a compound of Formula N:Formula N, or a salt thereof; nitrogen protecting a compound of Formula N:Formula N, or a salt thereof, thereby producing a compound of Formula O:Formula O, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, nitro reducing a compound of Formula O:Formula O, or a salt thereof, thereby producing a compound of Formula P:Formula P, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, installing an oxalylamide on a compound of Formula P:Attorney Docket No.: TGO-027WOFormula P, or a salt thereof, thereby producing a compound of Formula R:Formula R, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group and R12is C1-C6 alkyl, saponifying a compound of Formula R:or a salt thereof, thereby producing a compound of Formula H:Formula H, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, coupling a compound of Formula G:Formula G, or a salt thereof, with a compound of Formula H:Attorney Docket No.: TGO-027WOFormula H, or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, thereby producing a first salt of a compound of Formula I:Formula I, wherein R8is R6and R9is R7; removing the nitrogen protecting groups from the first salt of a compound of Formula I:Formula I, with a pharmaceutically acceptable acid, thereby producing a second salt of a compound of Formula I:Attorney Docket No.: TGO-027WOFormula I, wherein each of R8and R9is H; and free-basing a second salt of a compound of Formula I:thereby producing the compound of Formula X. Embodiment 57. A process for preparing a compound of Formula X:Formula X, comprising: hydrogenating a compound of Formula A1:Formula A1, or a salt thereof, wherein R1is a chiral auxiliary,Attorney Docket No.: TGO-027WO thereby producing a compound of Formula B:Formula B, or a salt thereof; protecting the nitrogen of a compound of Formula B:Formula B, or a salt thereof, thereby producing a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group; cross-coupling a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group, with a compound of Formula D:Formula D, or a salt thereof, R3is a boronic acid or a boronic ester, thereby producing a compound of Formula E:Formula E, or a salt thereof, wherein R2is a nitrogen protecting group; removing nitrogen protecting group from a compound of Formula E:Attorney Docket No.: TGO-027WOFormula E, or a salt thereof, wherein R2is a nitrogen protecting group, thereby producing a compound of Formula F:Formula F, or a salt thereof; enzymatically reducing a compound of Formula F:Formula F, or a salt thereof, thereby producing a compound of Formula G:Formula G, or a salt thereof; pivalamide protecting a compound of Formula J:Attorney Docket No.: TGO-027WOFormula J, or a salt thereof, thereby producing a compound of Formula K:or a salt thereof; installing an acetyl group on a compound of Formula K:Formula K, or a salt thereof, thereby producing a compound of Formula L:Formula L, or a salt thereof; reducing the carbonyl and pivalamide deprotecting of a compound of Formula L:Formula L, or a salt thereof, thereby producing a compound of Formula M:Formula M, or a salt thereof; nitrating a compound of Formula M:Attorney Docket No.: TGO-027WOor a salt thereof, thereby producing a compound of Formula N:Formula N, or a salt thereof; nitrogen protecting a compound of Formula N:Formula N, or a salt thereof, thereby producing a compound of Formula O:Formula O, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, nitro reducing a compound of Formula O:Formula O, or a salt thereof, thereby producing a compound of Formula P:Formula P, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, installing an oxalylamide on a compound of Formula P:Attorney Docket No.: TGO-027WOFormula P, or a salt thereof, thereby producing a compound of Formula R:Formula R, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group and R12is C1-C6 alkyl, saponifying a compound of Formula R:or a salt thereof, thereby producing a compound of Formula H:Formula H, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, coupling a compound of Formula G:Formula G, or a salt thereof, with a compound of Formula H:Attorney Docket No.: TGO-027WOFormula H, or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, thereby producing a first salt of a compound of Formula I:Formula I, wherein each of R8is R6and R9is R7; removing the nitrogen protecting groups from a first salt of a compound of FormulaFormula I, with a pharmaceutically acceptable acid, thereby producing a second salt of a compound of Formula I:Attorney Docket No.: TGO-027WOFormula I, wherein each of R8and R9are each H; and free-basing a second salt of a compound of Formula I:thereby producing the compound of Formula X. Embodiment 58. A process for preparing a compound of Formula X:Formula X, or a salt thereof, comprising: enzymatically amidating a compound of Formula A2:Formula A2, or a salt thereof, wherein R11is C1-C6alkyl,Attorney Docket No.: TGO-027WO thereby producing a compound of Formula B:Formula B, or a salt thereof; protecting the nitrogen of a compound of Formula B:Formula B, or a salt thereof, thereby producing a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group; cross-coupling a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group, with a compound of Formula D:Formula D, or a salt thereof, wherein R3is a boronic acid or a boronic ester, thereby producing a compound of Formula E:Formula E, or a salt thereof, wherein R2is a nitrogen protecting group; removing nitrogen protecting group from a compound of Formula E:Attorney Docket No.: TGO-027WOor a salt thereof, wherein R2is a nitrogen protecting group, thereby producing a compound of Formula F:Formula F, or a salt thereof; reducing a compound of Formula F:Formula F, or a salt thereof, thereby producing a compound of Formula G:Formula G, or a salt thereof; pivalamide protecting a compound of Formula J:Attorney Docket No.: TGO-027WOFormula J, or a salt thereof, thereby producing a compound of Formula K:or a salt thereof; installing an acetyl group on a compound of Formula K:Formula K, or a salt thereof, thereby producing a compound of Formula L:Formula L, or a salt thereof; reducing the carbonyl and pivalamide deprotecting of a compound of Formula L:Formula L, or a salt thereof, thereby producing a compound of Formula M:Formula M, or a salt thereof; nitrating a compound of Formula M:Attorney Docket No.: TGO-027WOor a salt thereof, thereby producing a compound of Formula N:Formula N, or a salt thereof; nitrogen protecting a compound of Formula N:Formula N, or a salt thereof, thereby producing a compound of Formula O:Formula O, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, nitro reducing a compound of Formula O:Formula O, or a salt thereof, thereby producing a compound of Formula P:Formula P, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, installing an oxalylamide on a compound of Formula P:Attorney Docket No.: TGO-027WOFormula P, or a salt thereof, thereby producing a compound of Formula R:Formula R, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group and R12is C1-C6 alkyl, saponifying a compound of Formula R:or a salt thereof, thereby producing a compound of Formula H:Formula H, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, coupling a compound of Formula G:Formula G, or a salt thereof, with a compound of Formula H:Attorney Docket No.: TGO-027WOFormula H, or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, thereby producing a first salt of a compound of Formula I:removing the nitrogen protecting groups from the first salt of a compound of Formula I:Formula I, with a pharmaceutically acceptable acid, thereby producing a second salt of a compound of Formula I:Attorney Docket No.: TGO-027WOFormula I, wherein each of R8and R9is H; and free-basing a second salt of a compound of Formula I:thereby producing the compound of Formula X. Embodiment 59. A process for preparing a compound of Formula X:Formula X, comprising: enzymatically amidating a compound of Formula A2:Formula A2, or a salt thereof, wherein R11is C1-C6alkyl,Attorney Docket No.: TGO-027WO thereby producing a compound of Formula B:Formula B, or a salt thereof; protecting the nitrogen of a compound of Formula B:Formula B, or a salt thereof, thereby producing a compound of Formula C:Formula C, or a salt thereof; cross-coupling a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group, with a compound of Formula D:Formula D, or a salt thereof, wherein R3is a boronic acid or a boronic ester, thereby producing a compound of Formula E:Formula E, or a salt thereof, wherein R2is a nitrogen protecting group; removing nitrogen protecting group from a compound of Formula E:Attorney Docket No.: TGO-027WOFormula E, or a salt thereof, wherein R2is a nitrogen protecting group, thereby producing a compound of Formula F:Formula F, or a salt thereof; enzymatically reducing a compound of Formula F:Formula F, or a salt thereof, thereby producing a compound of Formula G:Formula G, or a salt thereof; pivalamide protecting a compound of Formula J:Attorney Docket No.: TGO-027WOFormula J, or a salt thereof, thereby producing a compound of Formula K:or a salt thereof; installing an acetyl group on a compound of Formula K:Formula K, or a salt thereof, thereby producing a compound of Formula L:Formula L, or a salt thereof; reducing the carbonyl and pivalamide deprotecting of a compound of Formula L:Formula L, or a salt thereof, thereby producing a compound of Formula M:Formula M, or a salt thereof; nitrating a compound of Formula M:Attorney Docket No.: TGO-027WOor a salt thereof, thereby producing a compound of Formula N:Formula N, or a salt thereof; nitrogen protecting a compound of Formula N:Formula N, or a salt thereof, thereby producing a compound of Formula O:Formula O, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, nitro reducing a compound of Formula O:Formula O, or a salt thereof, thereby producing a compound of Formula P:Formula P, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, installing an oxalylamide on a compound of Formula P:Attorney Docket No.: TGO-027WOFormula P, or a salt thereof, thereby producing a compound of Formula R:Formula R, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group and R12is C1-C6 alkyl, saponifying a compound of Formula R:or a salt thereof, thereby producing a compound of Formula H:Formula H, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, coupling a compound of Formula G:Formula G, or a salt thereof, with a compound of Formula H:Attorney Docket No.: TGO-027WOFormula H, or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, thereby producing a first salt of a compound of Formula I:removing the nitrogen protecting groups from a first salt of a compound of Formulathereby producing a second salt of a compound of Formula I:Attorney Docket No.: TGO-027WOFormula I, wherein each of R8and R9is H; and free-basing a second salt of a compound of Formula I:thereby producing the compound of Formula X. Embodiment 60. A process for preparing a compound of Formula X:Formula X, or a salt thereof, comprising: free-basing a second salt of a compound of Formula I:Attorney Docket No.: TGO-027WO wherein eachwherein the second salt of the compound of Formula I is prepared by removing one or more nitrogen protecting groups from a first salt of a compound of Formula I:wherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group, wherein the first salt of the compound of Formula I is prepared by coupling a compound of Formula G:Formula G, or a salt thereof, with a compound of Formula H:Attorney Docket No.: TGO-027WOFormula H, or a salt thereof, wherein the compound of Formula G, or a salt thereof, is prepared by reducing a compound of Formula F:Formula F, or a salt thereof, wherein the compound of Formula F, or a salt thereof, is prepared by removing nitrogen protecting group from a compound of Formula E:Formula E, or a salt thereof, wherein R2is a nitrogen protecting group, wherein the compound of Formula E, or a salt thereof, is prepared by cross-coupling a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group, with a compound of Formula D:Formula D, or a salt thereof, wherein R3is a boronic acid or a boronic ester,Attorney Docket No.: TGO-027WO wherein the compound of Formula C, or a salt thereof, is prepared by protecting the nitrogen of a compound of Formula B:Formula B, or a salt thereof, wherein the compound of Formula B, or a salt thereof, is prepared by hydrogenating a compound of Formula A1:Formula A1, or a salt thereof, wherein R1is a chiral auxiliary. Embodiment 61. A process for preparing a compound of Formula X:Formula X, or a salt thereof, comprising: free-basing a second salt of a compound of Formula I:Formula I, wherein each of R8and R9is H, wherein the second salt of the compound of Formula I is prepared by removing one or more nitrogen protecting groups from a first salt of a compound of Formula I:Attorney Docket No.: TGO-027WOwherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group, wherein the first salt of the compound of Formula I is prepared by coupling a compound of Formula G:Formula G, or a salt thereof, with a compound of Formula H:Formula H, or a salt thereof, wherein the compound of Formula G, or a salt thereof, is prepared by enzymatically reducing a compound of Formula F:Attorney Docket No.: TGO-027WO or a salt thereof, wherein the compound of Formula F, or a salt thereof, is prepared by removing nitrogen protecting group from a compound of Formula E:Formula E, or a salt thereof, wherein R2is a nitrogen protecting group, wherein the compound of Formula E, or a salt thereof, is prepared by cross-coupling a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group, with a compound of Formula D:or a salt thereof, wherein R3is a boronic acid or a boronic ester, wherein the compound of Formula C, or a salt thereof, is prepared by protecting the nitrogen of a compound of Formula B:Formula B, or a salt thereof, wherein the compound of Formula B, or a salt thereof, is prepared by hydrogenating a compound of Formula A1:Formula A1, or a salt thereof, wherein R1is a chiral auxiliary. Embodiment 62. A process for preparing a compound of Formula X:Attorney Docket No.: TGO-027WOFormula X, or a salt thereof, comprising: free-basing a second salt of a compound of Formula I:wherein each of R8and R9is H, wherein the second salt of the compound of Formula I is prepared by removing one or more nitrogen protecting groups from a first salt of a compound of Formula I:Formula I, wherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group,Attorney Docket No.: TGO-027WO wherein the first salt of the compound of Formula I is prepared by coupling a compound of Formula G:or a salt thereof, with a compound of Formula H:Formula H, or a salt thereof, wherein the compound of Formula G, or a salt thereof, is prepared by reducing a compound of Formula F:Formula F, or a salt thereof, wherein the compound of Formula F, or a salt thereof, is prepared by removing nitrogen protecting group from a compound of Formula E:Formula E, or a salt thereof, wherein R2is a nitrogen protecting group,Attorney Docket No.: TGO-027WO wherein the compound of Formula E, or a salt thereof, is prepared by cross-coupling a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group, with a compound of Formula D:or a salt thereof, wherein R3is a boronic acid or a boronic ester, wherein the compound of Formula C, or a salt thereof, is prepared by protecting the nitrogen of a compound of Formula B:Formula B, or a salt thereof, wherein the compound of Formula B, or a salt thereof, is prepared by enzymatically amidating a compound of Formula A2:Formula A2, or a salt thereof, wherein R11is C1-C6alkyl. Embodiment 63. A process for preparing a compound of Formula X:Formula X, or a salt thereof, comprising: free-basing a second salt of a compound of Formula I:Attorney Docket No.: TGO-027WO wherein eachwherein the second salt of the compound of Formula I is prepared by removing one or more nitrogen protecting groups from a first salt of a compound of Formula I:wherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group, wherein the first salt of the compound of Formula I is prepared by coupling a compound of Formula G:Formula G, or a salt thereof, with a compound of Formula H:Attorney Docket No.: TGO-027WOFormula H, or a salt thereof, wherein the compound of Formula G, or a salt thereof, is prepared by enzymatically reducing a compound of Formula F:Formula F, or a salt thereof, wherein the compound of Formula F, or a salt thereof, is prepared by removing nitrogen protecting group from a compound of Formula E:Formula E, or a salt thereof, wherein R2is a nitrogen protecting group, wherein the compound of Formula E, or a salt thereof, is prepared by cross-coupling a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group, with a compound of Formula D:Formula D, or a salt thereof, wherein R3is a boronic acid or a boronic ester,Attorney Docket No.: TGO-027WO wherein the compound of Formula C, or a salt thereof, is prepared by protecting the nitrogen of a compound of Formula B:Formula B, or a salt thereof, wherein the compound of Formula B, or a salt thereof, is prepared by enzymatically amidating a compound of Formula A2:Formula A2, or a salt thereof, wherein R11is C1-C6alkyl. Embodiment 64. The process of any one of embodiments 60 to 63 wherein the compound of Formula H:or a salt thereof, is prepared by saponifying a compound of Formula R:Formula R, or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group,wherein the compound of Formula R, or a salt thereof, is prepared by installing anoxalylamide on a compound of Formula P:Formula P, or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group and R12is C1-C6alkyl,wherein the compound of Formula P, or a salt thereof, is prepared by nitro reducing acompound of Formula O:Attorney Docket No.: TGO-027WOFormula O, or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, wherein the compound of Formula O, or a salt thereof, is prepared by nitrogen protecting a compound of Formula N,Formula N, or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, wherein the compound of Formula N, or a salt thereof, is prepared by nitrating a compound of Formula M:or a salt thereof,wherein the compound of Formula M, or a salt thereof is prepared by reducing the carbonyland pivalamide deprotecting of a compound of Formula L:Formula L, or a salt thereof, wherein the compound of Formula L, or a salt thereof is prepared by installing an acetyl group on a compound of Formula K:or a salt thereof, wherein the compound of Formula K, or a salt thereof is prepared by pivalamide protecting a compound of Formula J:Attorney Docket No.: TGO-027WOFormula J, or a salt thereof. Embodiment 65. A process for preparing a compound of Formula X:or a salt thereof, comprising: free-basing a second salt of a compound of Formula I:Formula I, wherein each of R8and R9is H, wherein the second salt of the compound of Formula I is prepared by removing one or more nitrogen protecting groups from a first salt of a compound of Formula I:Attorney Docket No.: TGO-027WOwherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group, wherein the first salt of the compound of Formula I is prepared by coupling a compound of Formula G:Formula G, or a salt thereof, with a compound of Formula H:Formula H, or a salt thereof, wherein the compound of Formula G, or a salt thereof, is prepared by reducing a compound of Formula F: Formula F,Attorney Docket No.: TGO-027WO or a salt thereof, wherein the compound of Formula F, or a salt thereof, is prepared by removing nitrogen protecting group from a compound of Formula E:Formula E, or a salt thereof, wherein R2is a nitrogen protecting group, wherein the compound of Formula E, or a salt thereof, is prepared by cross-coupling a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group, with a compound of Formula D:or a salt thereof, wherein R3is a boronic acid or a boronic ester, wherein the compound of Formula C, or a salt thereof, is prepared by protecting the nitrogen of a compound of Formula B:Formula B, or a salt thereof, wherein the compound of Formula B, or a salt thereof, is prepared by hydrogenating a compound of Formula A1:Formula A1, or a salt thereof, wherein R1is a chiral auxiliary, wherein the compound of Formula H:Attorney Docket No.: TGO-027WOFormula H, or a salt thereof, is prepared by saponifying a compound of Formula R:or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, wherein the compound of Formula R, or a salt thereof, is prepared by installing anoxalylamide on a compound of Formula P:Formula P, or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group and R12is C1-C6alkyl, wherein the compound of Formula P, or a salt thereof, is prepared by nitro reducing acompound of Formula O:Formula O, or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, wherein the compound of Formula O, or a salt thereof, is prepared by nitrogen protecting a compound of Formula N,Formula N, or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group,Attorney Docket No.: TGO-027WO wherein the compound of Formula N, or a salt thereof, is prepared by nitrating a compound of Formula M:or a salt thereof, wherein the compound of Formula M, or a salt thereof is prepared by reducing thecarbonyl and pivalamide deprotecting of a compound of Formula L:Formula L, or a salt thereof, wherein the compound of Formula L, or a salt thereof is prepared by installing an acetyl group on a compound of Formula K:or a salt thereof, wherein the compound of Formula K, or a salt thereof is prepared by pivalamide protecting a compound of Formula J:Formula J, or a salt thereof. Embodiment 66. A process for preparing a compound of Formula X: Formula X,Attorney Docket No.: TGO-027WO or a salt thereof, comprising: free-basing a second salt of a compound of Formula I:Formula I, wherein each of R8and R9is H, wherein the second salt of the compound of Formula I is prepared by removing one or more nitrogen protecting groups from a first salt of a compound of Formula I:wherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group, wherein the first salt of the compound of Formula I is prepared by coupling a compound of Formula G:Formula G, or a salt thereof, with a compound of Formula H:Attorney Docket No.: TGO-027WOFormula H, or a salt thereof, wherein the compound of Formula G, or a salt thereof, is prepared by enzymatically reducing a compound of Formula F:Formula F, or a salt thereof, wherein the compound of Formula F, or a salt thereof, is prepared by removing nitrogen protecting group from a compound of Formula E:Formula E, or a salt thereof, wherein R2is a nitrogen protecting group, wherein the compound of Formula E, or a salt thereof, is prepared by cross-coupling a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group, with a compound of Formula D:Formula D, or a salt thereof, wherein R3is a boronic acid or a boronic ester,Attorney Docket No.: TGO-027WO wherein the compound of Formula C, or a salt thereof, is prepared by protecting the nitrogen of a compound of Formula B:Formula B, or a salt thereof, wherein the compound of Formula B, or a salt thereof, is prepared by hydrogenating a compound of Formula A1:Formula A1, or a salt thereof, wherein R1is a chiral auxiliary, wherein the compound of Formula H:or a salt thereof, is prepared by saponifying a compound of Formula R:Formula R, or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, wherein the compound of Formula R, or a salt thereof, is prepared by installing anoxalylamide on a compound of Formula P:Formula P, or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group and R12is C1-C6alkyl, wherein the compound of Formula P, or a salt thereof, is prepared by nitro reducing acompound of Formula O:Attorney Docket No.: TGO-027WOFormula O, or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, wherein the compound of Formula O, or a salt thereof, is prepared by nitrogen protecting a compound of Formula N,Formula N, or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, wherein the compound of Formula N, or a salt thereof, is prepared by nitrating a compound of Formula M:or a salt thereof, wherein the compound of Formula M, or a salt thereof is prepared by reducing thecarbonyl and pivalamide deprotecting of a compound of Formula L:Formula L, or a salt thereof, wherein the compound of Formula L, or a salt thereof is prepared by installing an acetyl group on a compound of Formula K:or a salt thereof, wherein the compound of Formula K, or a salt thereof is prepared by pivalamide protecting a compound of Formula J:Attorney Docket No.: TGO-027WOFormula J, or a salt thereof. Embodiment 67. A process for preparing a compound of Formula X:or a salt thereof, comprising: free-basing a second salt of a compound of Formula I:Formula I, wherein each of R8and R9is H, wherein the second salt of the compound of Formula I is prepared by removing one or more nitrogen protecting groups from a first salt of a compound of Formula I:Attorney Docket No.: TGO-027WOwherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group, wherein the first salt of the compound of Formula I is prepared by coupling a compound of Formula G:Formula G, or a salt thereof, with a compound of Formula H:Formula H, or a salt thereof, wherein the compound of Formula G, or a salt thereof, is prepared by reducing a compound of Formula F: Formula F,Attorney Docket No.: TGO-027WO or a salt thereof, wherein the compound of Formula F, or a salt thereof, is prepared by removing nitrogen protecting group from a compound of Formula E:Formula E, or a salt thereof, wherein R2is a nitrogen protecting group, wherein the compound of Formula E, or a salt thereof, is prepared by cross-coupling a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group, with a compound of Formula D:or a salt thereof, wherein R3is a boronic acid or a boronic ester, wherein the compound of Formula C, or a salt thereof, is prepared by protecting the nitrogen of a compound of Formula B:Formula B, or a salt thereof, wherein the compound of Formula B, or a salt thereof, is prepared by enzymatically amidating a compound of Formula A2:Formula A2, or a salt thereof, wherein R11is C1-C6alkyl, wherein the compound of Formula H:Attorney Docket No.: TGO-027WOFormula H, or a salt thereof, is prepared by saponifying a compound of Formula R:or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, wherein the compound of Formula R, or a salt thereof, is prepared by installing anoxalylamide on a compound of Formula P:Formula P, or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group and R12is C1-C6alkyl, wherein the compound of Formula P, or a salt thereof, is prepared by nitro reducing acompound of Formula O:Formula O, or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, wherein the compound of Formula O, or a salt thereof, is prepared by nitrogen protecting a compound of Formula N,Formula N, or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group,Attorney Docket No.: TGO-027WO wherein the compound of Formula N, or a salt thereof, is prepared by nitrating a compound of Formula M:or a salt thereof, wherein the compound of Formula M, or a salt thereof is prepared by reducing thecarbonyl and pivalamide deprotecting of a compound of Formula L:Formula L, or a salt thereof, wherein the compound of Formula L, or a salt thereof is prepared by installing an acetyl group on a compound of Formula K:or a salt thereof, wherein the compound of Formula K, or a salt thereof is prepared by pivalamide protecting a compound of Formula J:Formula J, or a salt thereof. Embodiment 68. A process for preparing a compound of Formula X: Formula X,Attorney Docket No.: TGO-027WO or a salt thereof, comprising: free-basing a second salt of a compound of Formula I:Formula I, wherein each of R8and R9is H, wherein the second salt of the compound of Formula I is prepared by removing one or more nitrogen protecting groups from a first salt of a compound of Formula I:wherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group, wherein the first salt of the compound of Formula I is prepared by coupling a compound of Formula G:Formula G, or a salt thereof, with a compound of Formula H:Attorney Docket No.: TGO-027WOFormula H, or a salt thereof, wherein the compound of Formula G, or a salt thereof, is prepared by enzymatically reducing a compound of Formula F:Formula F, or a salt thereof, wherein the compound of Formula F, or a salt thereof, is prepared by removing nitrogen protecting group from a compound of Formula E:Formula E, or a salt thereof, wherein R2is a nitrogen protecting group, wherein the compound of Formula E, or a salt thereof, is prepared by cross-coupling a compound of Formula C:Formula C, or a salt thereof, wherein R2is a nitrogen protecting group, with a compound of Formula D:Formula D, or a salt thereof, wherein R3is a boronic acid or a boronic ester,Attorney Docket No.: TGO-027WO wherein the compound of Formula C, or a salt thereof, is prepared by protecting the nitrogen of a compound of Formula B:Formula B, or a salt thereof, wherein the compound of Formula B, or a salt thereof, is prepared by enzymatically amidating a compound of Formula A2:Formula A2, or a salt thereof, wherein R11is C1-C6alkyl, wherein the compound of Formula H:or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, wherein the compound of Formula R, or a salt thereof, is prepared by installing anoxalylamide on a compound of Formula P:Formula P, or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group and R12is C1-C6alkyl, wherein the compound of Formula P, or a salt thereof, is prepared by nitro reducing acompound of Formula O:Attorney Docket No.: TGO-027WOFormula O, or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, wherein the compound of Formula O, or a salt thereof, is prepared by nitrogen protecting a compound of Formula N,Formula N, or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, wherein the compound of Formula N, or a salt thereof, is prepared by nitrating a compound of Formula M:or a salt thereof, wherein the compound of Formula M, or a salt thereof is prepared by reducing thecarbonyl and pivalamide deprotecting of a compound of Formula L:Formula L, or a salt thereof, wherein the compound of Formula L, or a salt thereof is prepared by installing an acetyl group on a compound of Formula K:or a salt thereof, wherein the compound of Formula K, or a salt thereof is prepared by pivalamide protecting a compound of Formula J:Attorney Docket No.: TGO-027WOor a salt thereof. Embodiment 69. A process for preparing a compound of Formula H:or a salt thereof, comprising: pivalamide protecting a compound of Formula J:Formula J, or a salt thereof, thereby producing a compound of Formula K:Formula K, or a salt thereof; installing an acetyl group on a compound of Formula K:Formula K, or a salt thereof, thereby producing a compound of Formula L:Formula L, or a salt thereof; reducing the carbonyl and pivalamide deprotecting of a compound of Formula L:Attorney Docket No.: TGO-027WOFormula L, or a salt thereof, thereby producing a compound of Formula M:Formula M, or a salt thereof; nitrating a compound of Formula M:Formula M, or a salt thereof, thereby producing a compound of Formula N:Formula N, or a salt thereof; nitrogen protecting a compound of Formula N:Formula N, or a salt thereof, thereby producing a compound of Formula O:Formula O, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, nitro reducing a compound of Formula O:Attorney Docket No.: TGO-027WO or a salt thereof, thereby producing a compound of Formula P:Formula P, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, installing an oxalylamide on a compound of Formula P:Formula P, or a salt thereof, thereby producing a compound of Formula R:R, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group and R12is C1-C6alkyl, saponifying a compound of Formula R:Formula R, or a salt thereof, thereby producing a compound of Formula H:or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, Embodiment 70. A process for preparing a compound of Formula H:Attorney Docket No.: TGO-027WOFormula H, or a salt thereof, comprising: saponifying a compound of Formula R:or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, wherein the compound of Formula R, or a salt thereof, is prepared by installing anoxalylamide on a compound of Formula P:Formula P, or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group and R12is C1-C6alkyl, wherein the compound of Formula P, or a salt thereof, is prepared by nitro reducing acompound of Formula O:Formula O, or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, wherein the compound of Formula O, or a salt thereof, is prepared by nitrogen protecting a compound of Formula N,Formula N, or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group,Attorney Docket No.: TGO-027WO wherein the compound of Formula N, or a salt thereof, is prepared by nitrating a compound of Formula M:or a salt thereof, wherein the compound of Formula M, or a salt thereof is prepared by reducing thecarbonyl and pivalamide deprotecting of a compound of Formula L:Formula L, or a salt thereof, wherein the compound of Formula L, or a salt thereof is prepared by installing an acetyl group on a compound of Formula K:or a salt thereof, wherein the compound of Formula K, or a salt thereof is prepared by pivalamide protecting a compound of Formula J:Formula J, or a salt thereof. Embodiment 71. A process for preparing a compound of Formula P:Formula P, or a salt thereof, comprising: pivalamide protecting a compound of Formula J:Attorney Docket No.: TGO-027WO thereby producing a compound of Formula K:or a salt thereof; installing an acetyl group on a compound of Formula K:Formula K, or a salt thereof, thereby producing a compound of Formula L:or a salt thereof; reducing the carbonyl and pivalamide deprotecting of a compound of Formula L:or a salt thereof, thereby producing a compound of Formula M:Formula M, or a salt thereof; nitrating a compound of Formula M:Formula M, or a salt thereof, thereby producing a compound of Formula N:Attorney Docket No.: TGO-027WOFormula N, or a salt thereof; nitrogen protecting a compound of Formula N:Formula N, or a salt thereof, thereby producing a compound of Formula O:Formula O, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, nitro reducing a compound of Formula O:Formula O, or a salt thereof, thereby producing a compound of Formula P:Formula P, or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group. Embodiment 72. A process for preparing a compound of Formula P:Formula P, or a salt thereof, comprising: nitro reducing a compound of Formula O:Attorney Docket No.: TGO-027WOFormula O, or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, wherein the compound of Formula O, or a salt thereof, is prepared by nitrogen protecting a compound of Formula N,Formula N, or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, wherein the compound of Formula N, or a salt thereof, is prepared by nitrating a compound of Formula M:or a salt thereof, wherein the compound of Formula M, or a salt thereof is prepared by reducing thecarbonyl and pivalamide deprotecting of a compound of Formula L:Formula L, or a salt thereof, wherein the compound of Formula L, or a salt thereof is prepared by installing an acetyl group on a compound of Formula K:or a salt thereof, wherein the compound of Formula K, or a salt thereof is prepared by pivalamide protecting a compound of Formula J:Attorney Docket No.: TGO-027WOFormula J, or a salt thereof. Embodiment 73. A process for preparing a compound of Formula B:Formula B, or a salt thereof, comprising: enzymatically amidating a compound of Formula A2:Formula A2, or a salt thereof, wherein R11is C1-C6alkyl, thereby producing a compound of Formula B, or a salt thereof. Embodiment 74. A process for preparing a compound of Formula G:Formula G,or a salt thereof, comprising: reducing a compound of Formula F:Formula F, or a salt thereof, thereby producing a compound of Formula G, or a salt thereof. Embodiment 75. A process for preparing a compound of Formula G:Attorney Docket No.: TGO-027WOor a salt thereof, comprising: enzymatically reducing a compound of Formula F:Formula F, or a salt thereof, thereby producing a compound of Formula G, or a salt thereof. Embodiment 76. A process for preparing a first salt of a compound of Formula I:Formula I, wherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group, comprising: coupling a compound of Formula G:Attorney Docket No.: TGO-027WOFormula G,or a salt thereof, with a compound of Formula H:Formula H, or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group. Embodiment 77. A process for preparing a second salt of a compound of Formula I:Formula I, wherein each of R8and R9is H, comprising removing one or more nitrogen protecting groups from a first salt of a compound of Formula I:Attorney Docket No.: TGO-027WOwherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group. Embodiment 78. The process of embodiment 76, wherein coupling of the compound of Formula G, or a salt thereof, with the compound of Formula H, or a salt thereof, produces a first salt of the compound of Formula I. Embodiment 79. The process of embodiment 77, wherein the first salt of the compound of Formula I is:. Embodiment 80. A process for preparing a compound of Formula X:Formula X, comprising: removing one or more nitrogen protecting groups from a first salt of a compound of Formula I:Attorney Docket No.: TGO-027WOwherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group, thereby producing a second salt of a compound of Formula I,wherein each of R8and R9is H. Embodiment 81. The process of any one of embodiments 1 to 80, wherein the first salt of the compound of Formula I is a crystalline form of the first salt of the compound of Formula I. Embodiment 82. The process of embodiment 81, wherein the first salt of the compound of Formula I is a formic acid salt of the compound of Formula I. Embodiment 83. The process of embodiment 81 or 82, wherein the first salt of the compound of Formula I is Compound A: .Attorney Docket No.: TGO-027WO Embodiment 84. The process of embodiment 83, wherein Compound A is a crystalline Form A of Compound A. Embodiment 85. The process of embodiment 84, wherein Form A has an X-ray powder diffraction (XRPD) pattern comprising one or more peaks at 2θ angles selected from 11.6±0.2, 11.7±0.2, 14.5±0.2, 16.6±0.2, 17.2±0.2, 17.5±0.2, 17.6±0.2, 19±0.2, and 24.9±0.2. Embodiment 86. The process of embodiment 84 or 85, wherein Form A has an X-ray powder diffraction (XRPD) pattern comprising 2θ angles of 11.6±0.2, 11.7±0.2, 14.5±0.2, 16.6±0.2, 17.2±0.2, 17.5±0.2, 17.6±0.2, 19±0.2, and 24.9±0.2. Embodiment 87. The process of any one of embodiments 1 to 86, wherein the second salt of the compound of Formula I is a crystalline form of the second salt of the compound of Formula I. Embodiment 88. The process of embodiment 87, wherein the second salt of the compound of Formula I is selected from a phosphoric acid salt of the compound of Formula I, a sulfuric acid salt of the compound of Formula I, and a benzoic acid salt of the compound of Formula I. Embodiment 89. The process of embodiment 87 or 88, wherein the second salt of the compound of Formula I is a formic acid salt of the compound of Formula I. Embodiment 90. The process of any one of embodiment 87 to 89, wherein the second salt of the compound of Formula I is Compound B:. Embodiment 91. The process of embodiment 90, wherein Compound B is a crystalline Form B of Compound B. Embodiment 92. The process of embodiment 91, wherein Form B has an X-ray powder diffraction (XRPD) pattern comprising one or more peaks at 2θ angles selected from 4.3±0.2,17.6±0.2, 19.3±0.2, 21.4±0.2, 21.4±0.2, 23±0.2, 23.3±0.2, 24.5±0.2, and 27.3±0.2. Embodiment 93. The process of embodiment 66 or 67, wherein Form B has an X-ray powder diffraction (XRPD) pattern comprising 2θ angles of 4.3±0.2, 8.6±0.2, 12.5±0.2,Attorney Docket No.: TGO-027WO 15.5±0.2, 17±0.2, 17.6±0.2, 19.3±0.2, 21.4±0.2, 21.4±0.2, 23±0.2, 23.3±0.2, 24.5±0.2, and 27.3±0.2. Embodiment 94. The process of any one of embodiments 1 to 93, wherein hydrogenating a compound of Formula A1 comprises contacting the compound of Formula A1 with a first catalyst. Embodiment 95. The process of embodiment 94, wherein hydrogenating the compound of Formula A1 comprises contacting the compound of Formula A1 with less than about 10 mol% of a first catalyst. Embodiment 96. The process of embodiment 94, wherein hydrogenating the compound of Formula A1 comprises contacting the compound of Formula A1 with less than about 5 mol% of a first catalyst. Embodiment 97. The process of embodiment 94, wherein hydrogenating the compound of Formula A1 comprises contacting the compound of Formula A1 with less than about 4 mol% of a first catalyst. Embodiment 98. The process of embodiment 94, wherein hydrogenating the compound of Formula A1 comprises contacting the compound of Formula A1 with less than about 3 mol% of a first catalyst. Embodiment 99. The process of embodiment 94, wherein hydrogenating the compound of Formula A1 comprises contacting the compound of Formula A1 with less than about 3 mol% of a first catalyst. Embodiment 100. The process of embodiment 94, wherein hydrogenating the compound of Formula A1 comprises contacting the compound of Formula A1 with about 2 mol% to about 3 mol% of a first catalyst. Embodiment 101. The process of embodiment 94, wherein hydrogenating the compound of Formula A1 comprises contacting the compound of Formula A1 with about 2.5 mol% of a first catalyst. Embodiment 102. The process of embodiment 94, wherein hydrogenating the compound of Formula A1 comprises contacting the compound of Formula A1 with less than about 2 mol% of a first catalyst. Embodiment 103. The process of embodiment 94, wherein hydrogenating the compound of Formula A1 comprises contacting the compound of Formula A1 with less than about 1.75 mol% of a first catalyst.Attorney Docket No.: TGO-027WO Embodiment 104. The process of embodiment 94, wherein hydrogenating the compound of Formula A1 comprises contacting the compound of Formula A1 with about 1 mol% to about 2 mol% of a first catalyst. Embodiment 105. The process of embodiment 94, wherein hydrogenating the compound of Formula A1 comprises contacting the compound of Formula A1 with about 1.5 mol% to about 2 mol% of a first catalyst. Embodiment 106. The process of embodiment 94, wherein hydrogenating the compound of Formula A1 comprises contacting the compound of Formula A1 with about 1.7 mol% of a first catalyst. Embodiment 107. The process of any one of embodiments 94 to 106, wherein the first catalyst is a palladium catalyst. Embodiment 108. The process of embodiment 107, wherein the first catalyst is a palladium (0) catalyst. Embodiment 109. The process of embodiment 107, wherein the first catalyst is palladium on carbon. Embodiment 110. The process of embodiment 107, wherein the first catalyst is about 5% by weight palladium on carbon. Embodiment 111. The process of embodiment 107, wherein the first catalyst is about 10% by weight palladium on carbon. Embodiment 112. The process of any one of embodiments 1 to 111, wherein hydrogenating the compound of Formula A1 comprises the use of a flow system. Embodiment 113. The process of embodiment 112, wherein hydrogenating the compound of Formula A1 comprises the use of a continuous flow system. Embodiment 114. The process of embodiment 112 or 113, wherein hydrogenating the compound of Formula A1 comprises the use of a micropacked bed reactor. Embodiment 115. The process of any one of embodiments 112 to 114, wherein hydrogenating the compound of Formula A1 is performed under flow hydrogenation conditions. Embodiment 116. The process of any one of embodiments 112 to 114, wherein hydrogenating the compound of Formula A1 is performed under continuous flow hydrogenation conditions.Attorney Docket No.: TGO-027WO Embodiment 117. The process of any one of embodiments 112 to 116, wherein hydrogenating the compound of Formula A1 comprises contacting the compound of Formula A1 with hydrogen gas. Embodiment 118. The process of any one of embodiments 112 to 116, wherein hydrogenating the compound of Formula A1 comprises contacting the compound of Formula A1 with hydrogen gas at a pressure of at least about 1.0 megapascal (MPa). Embodiment 119. The process of any one of embodiments 112 to 116, wherein hydrogenating the compound of Formula A1 comprises contacting the compound of Formula A1 with hydrogen gas at a pressure of at least about 2.0 megapascal (MPa). Embodiment 120. The process of any one of embodiments 112 to 116, wherein hydrogenating the compound of Formula A1 comprises contacting the compound of Formula A1 with hydrogen gas at a pressure of at least about 3.0 megapascal (MPa). Embodiment 121. The process of any one of embodiments 112 to 116, wherein hydrogenating the compound of Formula A1 comprises contacting the compound of Formula A1 with hydrogen gas at a pressure of between about 2.0 megapascal (MPa) and 4.0 megapascal (MPa). Embodiment 122. The process of any one of embodiments 112 to 116, wherein hydrogenating the compound of Formula A1 comprises contacting the compound of Formula A1 with hydrogen gas at a pressure of about 3.0 megapascal (MPa). Embodiment 123. The process of any one of embodiments 112 to 122, wherein hydrogenating a compound of Formula A1 comprises contacting the compound of Formula A1 with a second acid. Embodiment 124. The process of embodiment 123, wherein the second acid is an inorganic acid. Embodiment 125. The process of embodiment 123, wherein the second acid is hydrochloric acid. Embodiment 126. The process of any one of embodiments 1 to 111, wherein hydrogenating the compound of Formula A1 comprises the use of a batch system. Embodiment 127. The process of embodiment 126, wherein the batch system comprises the use of a parr hydrogenator. Embodiment 128. The process of embodiment 126 or 127, wherein hydrogenating a compound of Formula A1 comprises contacting the compound of Formula A1 with a second acid.Attorney Docket No.: TGO-027WO Embodiment 129. The process of embodiment 128, wherein the second acid is an inorganic acid. Embodiment 130. The process of embodiment 128, wherein the second acid is sulfuric acid. Embodiment 131. The process of embodiment 128, wherein the second acid is an organic acid. Embodiment 132. The process of embodiment 128, wherein the second acid is an organosulfuric acid. Embodiment 133. The process of embodiment 128, wherein the second acid is methanesulfonic acid (MSA). Embodiment 134. The process of any one of embodiments 1 to 133, wherein hydrogenating the compound of Formula A1 comprises contacting the compound of Formula A1 with hydrogen gas. Embodiment 135. The process of any one of embodiments 1 to 133, wherein hydrogenating the compound of Formula A1 comprises contacting the compound of Formula A1 with hydrogen gas at a pressure of at least about 1.0 megapascal (MPa). Embodiment 136. The process of any one of embodiments 1 to 133, wherein hydrogenating the compound of Formula A1 comprises contacting the compound of Formula A1 with hydrogen gas at a pressure of at least about 2.0 megapascal (MPa). Embodiment 137. The process of any one of embodiments 1 to 133, wherein hydrogenating the compound of Formula A1 comprises contacting the compound of Formula A1 with hydrogen gas at a pressure of at least about 2.5 megapascal (MPa). Embodiment 138. The process of any one of embodiments 1 to 133, wherein hydrogenating the compound of Formula A1 comprises contacting the compound of Formula A1 with hydrogen gas at a pressure of between about 2.0 megapascal (MPa) and 3.0 megapascal (MPa). Embodiment 139. The process of any one of embodiments 1 to 133, wherein hydrogenating the compound of Formula A1 comprises contacting the compound of Formula A1 with hydrogen gas at a pressure of about 2.5 megapascal (MPa). Embodiment 140. The process of any one of embodiments 1 to 139, wherein hydrogenating the compound of Formula A1 comprises elevating reaction temperature to about 55 °C to about 75 °C.Attorney Docket No.: TGO-027WO Embodiment 141. The process of any one of embodiments 1 to 139, wherein hydrogenating the compound of Formula A1 comprises elevating reaction temperature to about 60 °C to about 70 °C. Embodiment 142. The process of any one of embodiments 1 to 139, wherein hydrogenating the compound of Formula A1 comprises elevating reaction temperature to about 65 °C. Embodiment 143. The process of any one of embodiments 1 to 142, wherein hydrogenating the compound of Formula A1 comprises contacting the compound of Formula A1 with a first solvent. Embodiment 144. The process of embodiment 143, wherein the first solvent is a polar solvent. Embodiment 145. The process of embodiment 143, wherein the first solvent is tetrahydrofuran (THF). Embodiment 146. The process of embodiment any one of embodiments 1 to 145, wherein hydrogenating the compound of Formula A1 comprises contacting the compound of Formula A1 with a second solvent. Embodiment 147. The process of embodiment 146, wherein the second solvent is water. Embodiment 148. The process of any one of embodiments 1 to 147, wherein enzymatically amidating a compound of Formula A2 comprises contacting the compound of Formula A2 with a first enzyme. Embodiment 149. The process of embodiment 148, wherein enzymatically amidating a compound of Formula A2 comprises contacting the compound of Formula A2 with about 1% to about 5% by weight of the first enzyme. Embodiment 150. The process of embodiment 148, wherein enzymatically amidating a compound of Formula A2 comprises contacting the compound of Formula A2 with about 1% to about 3% by weight of the first enzyme. Embodiment 151. The process of embodiment 148, wherein enzymatically amidating a compound of Formula A2 comprises contacting the compound of Formula A2 with about 1.5% to about 2.5% by weight of the first enzyme. Embodiment 152. The process of embodiment 148, wherein enzymatically amidating a compound of Formula A2 comprises contacting the compound of Formula A2 with about 2% by weight of the first enzyme.Attorney Docket No.: TGO-027WO Embodiment 153. The process of any one of embodiments 148 to 152, wherein the first enzyme is an enzyme capable of catalyzing the enzymatic amidation of a compound of Formula A2 to a compound of Formula B. Embodiment 154. The process of any one of embodiments 148 to 152, wherein the first enzyme is pyridoxal phosphate. Embodiment 155. The process of any one of embodiments 148 to 154, wherein enzymatically amidating a compound of Formula A2 comprises contacting the compound of Formula A2 with a second enzyme. Embodiment 156. The process of embodiment 155, wherein enzymatically amidating a compound of Formula A2 comprises contacting the compound of Formula A2 with about 1% to about 5% by weight of the second enzyme. Embodiment 157. The process of embodiment 155, wherein enzymatically amidating a compound of Formula A2 comprises contacting the compound of Formula A2 with about 1% to about 3% by weight of the second enzyme. Embodiment 158. The process of embodiment 155, wherein enzymatically amidating a compound of Formula A2 comprises contacting the compound of Formula A2 with about 1.5% to about 2.5% by weight of the second enzyme. Embodiment 159. The process of embodiment 155, wherein enzymatically amidating a compound of Formula A2 comprises contacting the compound of Formula A2 with about 2% by weight of the second enzyme. Embodiment 160. The process of any one of embodiments 155 to 159, wherein the second enzyme is an amine transaminase. Embodiment 161. The process of embodiment 160, wherein the second enzyme is a naturally occurring (wild-type) amine transaminase. Embodiment 162. The process of embodiment 160, wherein the second enzyme is an engineered amine transaminase capable of catalyzing the enzymatic amidation of a compound of Formula A2 to a compound of Formula B. Embodiment 163. The process of embodiment 160, wherein the second enzyme is ATA- 22403. Embodiment 164. The process of any one of embodiments 1 to 163, wherein protecting the nitrogen of a compound of Formula B comprises contacting the compound of Formula B with a first base.Attorney Docket No.: TGO-027WO Embodiment 165. The process of embodiment 164, wherein the first base is a pyridine base. Embodiment 166. The process of embodiment 164, wherein the first base is dimethylaminopyridine (DMAP). Embodiment 167. The process of any one of embodiments 1 to 166, wherein protecting the nitrogen of a compound of Formula B comprises contacting the compound of Formula B with a second base. Embodiment 168. The process of embodiment 167, wherein the second base is an amine base. Embodiment 169. The process of embodiment 167, wherein the second base is triethylamine (TEA). Embodiment 170. The process of any one of embodiments 1 to 169, wherein protecting the nitrogen of a compound of Formula B comprises contacting the compound of Formula B with a third solvent. Embodiment 171. The process of embodiment 170, wherein the third solvent is a polar solvent. Embodiment 172. The process of embodiment 170, wherein the third solvent is acetonitrile. Embodiment 173. The process of embodiment 170, wherein the third solvent is a halogenated solvent. Embodiment 174. The process of embodiment 170, wherein the third solvent is dichloromethane (DCM). Embodiment 175. The process of any one of embodiments 1 to 174, wherein protecting the nitrogen of a compound of Formula B comprises elevating reaction temperature to about 40 °C to about 50 °C. Embodiment 176. The process of any one of embodiments 1 to 174, wherein protecting the nitrogen of a compound of Formula B comprises elevating reaction temperature to about 45 °C. Embodiment 177. The process of any one of embodiments 1 to 174, wherein protecting the nitrogen of a compound of Formula B comprises elevating reaction temperature to about 20 °C to 30 °C.Attorney Docket No.: TGO-027WO Embodiment 178. The process of any one of embodiments 1 to 174, wherein protecting the nitrogen of a compound of Formula B comprises elevating reaction temperature to about 25 °C to about 30 °C. Embodiment 179. The process of any one of embodiments 1 to 178, wherein cross- coupling a compound of Formula C with a compound of Formula D comprises converting the compound of Formula C to a compound of Formula C-1:Formula C-1, or a salt thereof, wherein: R2is a nitrogen protecting group; and R4is alkyl sulfonate, haloalkyl sulfonate, or aryl sulfonate. Embodiment 180. The process of embodiment 179, wherein converting the compound of Formula C to a compound of Formula C-1, or a salt thereof, comprises contacting the compound of Formula C with a dehydrating agent. Embodiment 181. The process of embodiment 180, wherein the dehydrating agent is a sulfonimide. Embodiment 182. The process of embodiment 180, wherein the dehydrating agent is 1,1,1-trifluoro-N-phenyl-N-(trifluoromethanesulfonyl)methanesulfonamide (PhNTf2). Embodiment 183. The process of any one of embodiments 1-182, wherein converting the compound of Formula C to a compound of Formula C-1, or a salt thereof, comprises contacting the compound of Formula C with a third base. Embodiment 184. The process of embodiment 183, wherein the third base is an inorganic Embodiment 185. The process of embodiment 183, wherein the third base is an organic base. Embodiment 186. The process of embodiment 183, wherein the third base is a lithium base. Embodiment 187. The process of embodiment 183, wherein the third base is an amine base. Embodiment 188. The process of embodiment 183, wherein the third base is lithium bis(trimethylsilyl)amide (LiHMDS).Attorney Docket No.: TGO-027WO Embodiment 189. The process of any one of embodiments 1-188, wherein converting the compound of Formula C to a compound of Formula C-1, or a salt thereof, comprises contacting the compound of Formula C with a fourth solvent. Embodiment 190. The process of embodiment 189, wherein the fourth solvent is a polar solvent. Embodiment 191. The process of embodiment 189, wherein the fourth solvent is tetrahydrofuran (THF). Embodiment 192. The process of any one of embodiments 1 to 191, wherein converting the compound of Formula C to a compound of Formula C-1, or a salt thereof, comprises lowering reaction temperature to below about 0º C. Embodiment 193. The process of any one of embodiments 1-191, wherein converting the compound of Formula C to a compound of Formula C-1, or a salt thereof, comprises lowering reaction temperature to about -20º C to about -10 °C. Embodiment 194. The process of any one of embodiments 1 to 193, wherein cross- coupling a compound of Formula C with a compound of Formula D comprises contacting a compound of Formula C-1, or a salt thereof, with a compound of Formula D, or a salt thereof. Embodiment 195. The process of any one of embodiments 1 to 194, wherein cross- coupling a compound of Formula C with a compound of Formula D comprises contacting a compound of Formula C-1, or a salt thereof, with the compound of Formula D, or a salt thereof, in the presence of a second catalyst. Embodiment 196. The process of embodiment 195, wherein cross-coupling a compound of Formula C with a compound of Formula D comprises contacting a compound of Formula C-1, or a salt thereof, with the compound of Formula D, or a salt thereof, in the presence of less than about 10 mol% of the second catalyst. Embodiment 197. The process of embodiment 195, wherein cross-coupling a compound of Formula C with a compound of Formula D comprises contacting a compound of Formula C-1, or a salt thereof, with the compound of Formula D, or a salt thereof, in the presence of less than about 5 mol% of the second catalyst. Embodiment 198. The process of embodiment 195, wherein cross-coupling a compound of Formula C with a compound of Formula D comprises contacting a compound of Formula C-1, or a salt thereof, with the compound of Formula D, or a salt thereof, in the presence of about 5 mol% of the second catalyst.Attorney Docket No.: TGO-027WO Embodiment 199. The process of embodiment 195, wherein cross-coupling a compound of Formula C with a compound of Formula D comprises contacting a compound of Formula C-1, or a salt thereof, with the compound of Formula D, or a salt thereof, in the presence of about 4.5 mol% of the second catalyst. Embodiment 200. The process of embodiment 195, wherein cross-coupling a compound of Formula C with a compound of Formula D comprises contacting a compound of Formula C-1, or a salt thereof, with the compound of Formula D, or a salt thereof, in the presence of about 4 mol% of the second catalyst. Embodiment 201. The process of embodiment 195, wherein cross-coupling a compound of Formula C with a compound of Formula D comprises contacting a compound of Formula C-1, or a salt thereof, with the compound of Formula D, or a salt thereof, in the presence of about 3.5 mol% of the second catalyst. Embodiment 202. The process of embodiment 195, wherein cross-coupling a compound of Formula C with a compound of Formula D comprises contacting a compound of Formula C-1, or a salt thereof, with the compound of Formula D, or a salt thereof, in the presence of about 3 mol% of the second catalyst. Embodiment 203. The process of embodiment 195, wherein cross-coupling a compound of Formula C with a compound of Formula D comprises contacting a compound of Formula C-1, or a salt thereof, with the compound of Formula D, or a salt thereof, in the presence of about 2.5 mol% of the second catalyst. Embodiment 204. The process of any one of embodiments 195 to 203, wherein the second catalyst is a palladium catalyst. Embodiment 205. The process of embodiment 204, wherein the second catalyst is a palladium (II) catalyst.Embodiment 206. The process of embodiment 204, wherein the second catalyst is [1,1 -bis(diphenylphosphino)ferrocene]dichloropalladium(II). Embodiment 207. The process of any one of embodiments 1 to 206, wherein cross- coupling a compound of Formula C with a compound of Formula D comprises contacting a compound of Formula C-1, or a salt thereof, with the compound of Formula D, or a salt thereof, in the presence of a fourth base. Embodiment 208. The process of embodiment 207, wherein the fourth base is an inorganic base.Attorney Docket No.: TGO-027WO Embodiment 209. The process of embodiment 207, wherein the fourth base is a carbonate base. Embodiment 210. The process of embodiment 207, wherein the fourth base is Na2CO3. Embodiment 211. The process of any one of embodiments 1 to 210, wherein cross- coupling a compound of Formula C with a compound of Formula D comprises contacting a compound of Formula C-1, or a salt thereof, with the compound of Formula D, or a salt thereof, in the presence of a fifth solvent. Embodiment 212. The process of embodiment 211, wherein the fifth solvent is a polar solvent. Embodiment 213. The process of embodiment 211, wherein the fifth solvent is tetrahydrofuran (THF). Embodiment 214. The process of any one of embodiments 1 to 213, wherein cross- coupling a compound of Formula C with a compound of Formula D comprises contacting a compound of Formula C-1, or a salt thereof, with the compound of Formula D, or a salt thereof, in the presence of a sixth solvent. Embodiment 215. The process of embodiment 214, wherein the sixth solvent is water. Embodiment 216. The process of any one of embodiments 1 to 215, wherein removing nitrogen protecting group from a compound of Formula E comprises contacting the compound of Formula E with a first acid. Embodiment 217. The process of embodiment 216, wherein the first acid is an inorganic acid. Embodiment 218. The process of embodiment 216, wherein the first acid is hydrochloric acid. Embodiment 219. The process of any one of embodiments 1 to 218, wherein removing nitrogen protecting group from a compound of Formula E comprises contacting the compound of Formula E with a seventh solvent. Embodiment 220. The process of embodiment 219, wherein the seventh solvent is a protic solvent. Embodiment 221. The process of embodiment 219, wherein the seventh solvent is an alcohol. Embodiment 222. The process of embodiment 219, wherein the seventh solvent is methanol (MeOH).Attorney Docket No.: TGO-027WO Embodiment 223. The process of any one of embodiments 1 to 222, wherein reducing a compound of Formula F comprises contacting the compound of Formula F with a reducing agent. Embodiment 224. The process of embodiment 223, wherein the reducing agent is a hydride reducing agent. Embodiment 225. The process of embodiment 223, wherein the reducing agent is a borohydride reducing agent. Embodiment 226. The process of embodiment 223, wherein the reducing agent is sodium borohydride (NaBH4). Embodiment 227. The process of any one of embodiments 1 to 226, wherein reducing a compound of Formula F comprises contacting the compound of Formula F with an eighth solvent. Embodiment 228. The process of embodiment 227, wherein the eighth solvent is a protic solvent. Embodiment 229. The process of embodiment 228, wherein the eighth solvent is methanol (MeOH). Embodiment 230. The process of any one of embodiments 1 to 229, wherein enzymatically reducing a compound of Formula F comprises contacting the compound of Formula F with a third enzyme. Embodiment 231. The process of embodiment 230, wherein the third enzyme is an imine reductase. Embodiment 232. The process of embodiment 231, wherein the third enzyme is a naturally occurring (wild-type) imine reductase. Embodiment 233. The process of embodiment 231, wherein the third enzyme is an engineered imine reductase capable of catalyzing the reducing of a compound of Formula F to a compound of Formula G. Embodiment 234. The process of embodiment 231, wherein the third enzyme is IRED- 23182. Embodiment 235. The process of any one of embodiments 1 to 234, wherein enzymatically reducing a compound of Formula F comprises contacting the compound of Formula F with a fourth enzyme. Embodiment 236. The process of embodiment 235, wherein the fourth enzyme is a glutamate dehydrogenase.Attorney Docket No.: TGO-027WO Embodiment 237. The process of any one of embodiments 1 to 236, wherein enzymatically reducing a compound of Formula F comprises contacting the compound of Formula F with nicotinamide adenine dinucleotide phosphate (NADP). Embodiment 238. The process of any one of embodiments 1 to 237, wherein enzymatically reducing a compound of Formula F comprises contacting the compound of Formula F comprises contacting the compound of Formula F with a sugar. Embodiment 239. The process of embodiment 238, wherein the sugar is glucose. Embodiment 240. The process of any one of embodiments 1 to 239, wherein enzymatically reducing a compound of Formula F comprises contacting the compound of Formula F comprises contacting the compound of Formula F with a buffer. Embodiment 241. The process of embodiment 240, wherein the buffer comprises K2HPO4. Embodiment 242. The process of embodiment 240, wherein the buffer comprises KH2PO4. Embodiment 243. The process of embodiment 240, wherein the buffer comprises K2HPO4and KH2PO4. Embodiment 244. The process of any one of embodiments 1 to 243, wherein coupling a compound of Formula G with a compound of Formula H comprises contacting the compound of Formula G, or a salt thereof, with a compound of Formula H, or a salt thereof. Embodiment 245. The process of embodiment 244, wherein coupling a compound of Formula G with a compound of Formula H comprises contacting the compound of Formula G, or a salt thereof, with a compound of Formula H, or a salt thereof, having a molar ratio of about 1:1 to about 1:1.2. Embodiment 246. The process of embodiment 244, wherein coupling a compound of Formula G with a compound of Formula H comprises contacting the compound of Formula G, or a salt thereof, with a compound of Formula H, or a salt thereof, having a molar ratio of about 1:1.1. Embodiment 247. The process of any one of embodiments 1 to 246, wherein coupling a compound of Formula G with a compound of Formula H comprises contacting the compound of Formula G, or a salt thereof, with a compound of Formula H, or a salt thereof, in the presence of a coupling reagent. Embodiment 248. The process of embodiment 247, wherein the coupling reagent is an anhydride coupling reagent; a triazole-based coupling reagent; a carbodiimide couplingAttorney Docket No.: TGO-027WO reagent; an imidazolium coupling reagent; a phosphonium salt coupling reagent; or a pyridinium salt coupling reagent. Embodiment 249. The process of embodiment 247, wherein the coupling reagent is a triazole-based coupling reagent. Embodiment 250. The process of embodiment 247, wherein the coupling reagent is 1- [bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU); N,N,N',N'-tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate (HBTU); O-(1H-6-chlorobenzotriazole-1-yl)-1,1,3,3- tetramethyluronium hexafluorophosphate (HCTU); or 2-(1H-benzotriazole-1-yl)-1,1,3,3- tetramethylaminium tetrafluoroborate (TBTU). Embodiment 251. The process of embodiment 247, wherein the coupling reagent is 1- [bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU) or 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethylaminium tetrafluoroborate (TBTU). Embodiment 252. The process of embodiment 247, wherein the coupling reagent is 2- (1H-benzotriazole-1-yl)-1,1,3,3-tetramethylaminium tetrafluoroborate (TBTU). Embodiment 253. The process of any one of embodiments 247 to 252, wherein the compound of Formula G and the coupling reagent have a molar ratio of about 1:1 to about 1:2. Embodiment 254. The process of any one of embodiments 247 to 252, wherein the compound of Formula G and the coupling reagent have a molar ratio of about 1:1.5. Embodiment 255. The process of any one of embodiments 1 to 254, wherein coupling a compound of Formula G with a compound of Formula H comprises contacting the compound of Formula G, or a salt thereof, with a compound of Formula H, or a salt thereof, in the presence of a fifth base. Embodiment 256. The process of embodiment 255, wherein the fifth base is an organic base. Embodiment 257. The process of embodiment 255, wherein the fifth base is an organic Embodiment 258. The process of embodiment 255, wherein the fifth base is N- methylmorpholine (NMM). Embodiment 259. The process of any one of embodiments 1 to 258, wherein coupling a compound of Formula G with a compound of Formula H comprises contacting theAttorney Docket No.: TGO-027WOcompound of Formula G, or a salt thereof, with a compound of Formula H, or a salt thereof,in the presence of a ninth solvent. Embodiment 260. The process of embodiment 259, wherein the ninth solvent is a protic solvent. Embodiment 261. The process of embodiment 259, wherein the ninth solvent is acetonitrile. Embodiment 262. The process of any one of embodiments 1 to 260, wherein coupling a compound of Formula G with a compound of Formula H comprises contacting thecompound of Formula G, or a salt thereof, with a compound of Formula H, or a salt thereof,in the presence of a tenth solvent. Embodiment 263. The process of embodiment 262, wherein the tenth solvent is a polar solvent. Embodiment 264. The process of embodiment 262, wherein the tenth solvent is an ether solvent. Embodiment 265. The process of embodiment 262, wherein the tenth solvent is methyl tert-butyl ether. Embodiment 266. The process of any one of embodiments 1 to 265, wherein coupling a compound of Formula G with a compound of Formula H comprises contacting the compound of Formula G with a compound of Formula H, or a salt thereof, in the presence of a third acid. Embodiment 267. The process of embodiment 266, wherein the third acid is formic acid. Embodiment 268. The process of any one of embodiments 1 to 267, wherein coupling a compound of Formula G with a compound of Formula H results in a first salt of Formula I. Embodiment 269. The process of embodiment 268, wherein the first salt of Formula I is:Attorney Docket No.: TGO-027WO Embodiment 270. The process of any one of embodiments 1 to 269, wherein removing one or more nitrogen protecting groups from a first salt of a compound of Formula I comprises contacting the first salt of the compound of Formula I with a fourth acid. Embodiment 271. The process of embodiment 270, wherein the fourth acid is an inorganic acid. Embodiment 272. The process of embodiment 270, wherein the fourth acid is phosphoric acid (H3PO4), sulfuric acid (H2SO4) or benzoic acid. Embodiment 273. The process of embodiment 270, wherein the fourth acid is phosphoric acid (H3PO4). Embodiment 274. The process of any one of embodiments 1 to 273, wherein removing one or more nitrogen protecting groups from a first salt of a compound of Formula I comprises contacting the first salt of the compound of Formula I with an eleventh solvent. Embodiment 275. The process of embodiment 274, wherein the eleventh solvent is a polar solvent. Embodiment 276. The process of embodiment 274, wherein the eleventh solvent is acetone. Embodiment 277. The process of any one of embodiments 1 to 276, wherein removing one or more nitrogen protecting groups from a first salt of a compound of Formula I results in a second salt of a compound of Formula I. Embodiment 278. The process of embodiment 277, wherein the second salt of a. Embodiment 279. The process of any one of embodiments 1 to 278, wherein free-basing a second salt of a compound of Formula I comprises contacting the second salt of the compound of Formula I with a twelfth solvent. Embodiment 280. The process of embodiment 279, wherein the twelfth solvent is an apolar solvent. Embodiment 281. The process of embodiment 280, wherein the twelfth solvent is n- heptane.Attorney Docket No.: TGO-027WO Embodiment 282. The process of any one of embodiments 1 to 281, wherein free-basing a second salt of a compound of Formula I comprises contacting the second salt of the compound of Formula I with a sixth base. Embodiment 283. The process of embodiment 282, wherein the sixth base is an inorganic base. Embodiment 284. The process of embodiment 282, wherein the sixth base is a carbonate base. Embodiment 285. The process of embodiment 282, wherein the sixth base is sodium carbonate. Embodiment 286. The process of any one of embodiments 1 to 285, wherein free-basing a second salt of a compound of Formula I comprises contacting the second salt of the compound of Formula I with a thirteenth solvent. Embodiment 287. The process of embodiment 286, wherein the thirteenth solvent is a polar solvent. Embodiment 288. The process of embodiment 286, wherein the thirteenth solvent is a ketone solvent. Embodiment 289. The process of embodiment 286, wherein the thirteenth solvent is methyl ethyl ketone (MEK). Embodiment 290. The process of any one of embodiments 40 to 289, wherein pivalamide protecting a compound of Formula J, or a salt thereof, comprises contacting the compound of Formula J, or a salt thereof, with pivaloyl chloride (trimethylacetyl chloride). Embodiment 291. The process of any one of embodiments 40 to 290, wherein pivalamide protecting a compound of Formula J, or a salt thereof, comprises contacting the compound of Formula J, or a salt thereof, with a seventh base. Embodiment 292. The process of embodiment 291, wherein the seventh base is an amine base. Embodiment 293. The process of embodiment 291, wherein the seventh base is triethylamine (TEA). Embodiment 294. The process of any one of embodiments 40 to 293, wherein pivalamide protecting a compound of Formula J, or a salt thereof, comprises lowering the reaction temperature to between about -10 °C and about 10 °C. Embodiment 295. The process of any one of embodiments 40 to 294, wherein converting the compound of Formula K, or a salt thereof, to a compound of Formula L, or a saltAttorney Docket No.: TGO-027WO thereof, comprises contacting the compound of Formula K, or a salt thereof with a fourteenth solvent. Embodiment 296. The process of embodiment 295, wherein the fourteenth solvent is an organic solvent. Embodiment 297. The process of embodiment 296, wherein the fourteenth solvent is a polar solvent. Embodiment 298. The process of embodiment 296, wherein the fourteenth solvent is tetrahydrofuran (THF). Embodiment 299. The process of any one of embodiments 40 to 298, wherein converting the compound of Formula K, or a salt thereof, to a compound of Formula L, or a salt thereof, comprises contacting the compound of Formula K, or a salt thereof, with an eighth base. Embodiment 300. The process of embodiment 299, wherein the eighth base is a lithium base. Embodiment 301. The process of embodiment 299, wherein the eighth base is n- butyllithium. Embodiment 302. The process of any one of embodiments 40 to 301, wherein contacting the compound of Formula K with the eighth base comprises lowering reaction temperature to below 0° C. Embodiment 303. The process of any one of embodiments 40 to 301, wherein contacting the compound of Formula K with the eighth base comprises lowering reaction temperature to between about -10 ºC to about 0 °C. Embodiment 304. The process of any one of embodiments 40 to 303, wherein converting the compound of Formula K, or a salt thereof, to a compound of Formula L, or a salt thereof, comprises contacting the compound of Formula K, or a salt thereof with N- Methoxy-N-methylacetamide. Embodiment 305. The process of embodiment 304, wherein contacting the compound of Formula K, or a salt thereof with N-Methoxy-N-methylacetamide comprises lowering reaction temperature to below about -40 ºC. Embodiment 306. The process of embodiment 304, wherein contacting the compound of Formula K, or a salt thereof with N-Methoxy-N-methylacetamide comprises lowering reaction temperature to between about -60 ºC to about -40 °C.Attorney Docket No.: TGO-027WO Embodiment 307. The process of any one of embodiments 40 to 306, wherein converting the compound of Formula K, or a salt thereof, to a compound of Formula L, or a salt thereof is performed in a continuous stirred tank reactor or a series of continuous stirred tank reactors. Embodiment 308. The process of any one of embodiments 40 to 307, wherein reducing the carbonyl group and deprotecting the pivalamide of a compound of Formula L or a salt thereof, comprises contacting the compound of Formula L with hydrazine hydrate. Embodiment 309. The process of any one of embodiments 40 to 308, wherein reducing the carbonyl group and deprotecting the pivalamide of a compound of Formula L or a salt thereof, comprises contacting the compound of Formula L with a ninth base. Embodiment 310. The process of embodiment 309, wherein the ninth base is an inorganic base. Embodiment 311. The process of embodiment 309, wherein the ninth base is a hydroxide base. Embodiment 312. The process of embodiment 309, wherein the ninth base is KOH. Embodiment 313. The process of any one of embodiments 40 to 312, wherein reducing the carbonyl group and deprotecting the pivalamide of a compound of Formula L or a salt thereof, comprises contacting the compound of Formula L with a fifteenth solvent. Embodiment 314. The process of embodiment 313, wherein the fifteenth solvent is an organic solvent. Embodiment 315. The process of embodiment 314, wherein the fifteenth solvent is a polar solvent. Embodiment 316. The process of any one of embodiments 313 to 315, wherein the fifteenth solvent is a high-boiling point solvent. Embodiment 317. The process of any one of embodiments 313 to 316, wherein the fifteenth solvent is triethylene glycol. Embodiment 318. The process of any one of embodiments 40 to 317, wherein reducing the carbonyl group and deprotecting the pivalamide of a compound of Formula L or a salt thereof, comprises elevating reaction temperature to higher than 180 °C. Embodiment 319. The process of any one of embodiments 40 to 318, wherein reducing the carbonyl group and deprotecting the pivalamide of a compound of Formula L or a salt thereof, comprises elevating reaction temperature to between about 180 °C to about 220 °C.Attorney Docket No.: TGO-027WO Embodiment 320. The process of any one of embodiments 40 to 318, wherein reducing the carbonyl group and deprotecting the pivalamide of a compound of Formula L or a salt thereof, comprises elevating reaction temperature to between about 190 °C to about 210 °C. Embodiment 321. The process of any one of embodiments 40 to 320, wherein reducing the carbonyl group and deprotecting the pivalamide of a compound of Formula L or a salt thereof is performed in a plug flow reactor (PFR). Embodiment 322. The process of any one of embodiments 40 to 321, wherein nitration of a compound of Formula M, or a salt thereof, comprises contacting the compound of Formula M with a mixture of sulfuric acid (H2SO4) and nitric acid (HNO3). Embodiment 323. The process of any one of embodiments 40 to 322, wherein nitration of a compound of Formula M, or a salt thereof, is performed in a plug flow reactor (PFR). Embodiment 324. The process of any one of embodiments 40 to 323, wherein nitrogen protection of a compound of Formula N, or a salt thereof, comprises contacting the compound of Formula N with a second nitrogen protecting group reagent. Embodiment 325. The process of embodiment 324, wherein the second nitrogen protecting group reagent comprises a carbamate. Embodiment 326. The process embodiment 324, wherein the second nitrogen protecting group reagent comprises .Embodiment 327. The process of embodiment 324, wherein the second nitrogen protecting group reagent is .Embodiment 328. The process of any one of embodiments 40 to 327, wherein nitrogen protection of a compound of Formula N, or a salt thereof, comprises contacting the compound of Formula N with an eighth base. Embodiment 329. The process of embodiment 328, wherein the eighth base is an amine base (e.g., triethylamine (TEA), diisopropylethylamine (DIPEA), 4-dimethylamino pyridine (DMAP). Embodiment 330. The process of embodiment 328, wherein the eighth base is dimethylamino pyridine (DMAP). Embodiment 331. The process of any one of embodiments 40 to 330, wherein nitrogen protection of a compound of Formula N, or a salt thereof, comprises contacting the compound of Formula N with a sixteenth solvent.Attorney Docket No.: TGO-027WO Embodiment 332. The process of embodiment 331, wherein the sixteenth solvent is an organic solvent. Embodiment 333. The process of embodiment 331, wherein the sixteenth solvent is tetrahydrofuran (THF). Embodiment 334. The process of any one of embodiments 40 to 333, wherein nitrogen protection of a compound of Formula N, or a salt thereof, comprises lowering the reaction temperature to below about 20 °C. Embodiment 335. The process of any one of embodiments 40 to 333, wherein nitrogen protection of a compound of Formula N, or a salt thereof, comprises lowering the reaction temperature to between about 8 °C and about 18 °C. Embodiment 336. The process of any one of embodiments 40 to 335, wherein nitro reduction of a compound of Formula P, or a salt thereof, comprises contacting the compound of Formula P, or a salt thereof, with a third catalyst. Embodiment 337. The process of any one of embodiments 40 to 335, wherein hydrogenating the compound of Formula P, or a salt thereof, comprises contacting the compound of Formula P with less than about 40 % w / w of a third catalyst. Embodiment 338. The process of any one of embodiments 40 to 335, wherein hydrogenating the compound of Formula P, or a salt thereof, comprises contacting the compound of Formula P, or a salt thereof, with about 20 % w / w to about 35 % w / w of a third catalyst. Embodiment 339. The process of any one of embodiments 40 to 335, wherein hydrogenating the compound of Formula P, or a salt thereof, comprises contacting the compound of Formula P, or a salt thereof, with about 30 % w / w of a third catalyst. Embodiment 340. The process of any one of embodiments 40 to 339, wherein the third catalyst is a nickel catalyst. Embodiment 341. The process of any one of embodiments 40 to 339, wherein the third catalyst is a nickel (0) catalyst. Embodiment 342. The process of any one of embodiments 40 to 339, wherein the third catalyst is nickel on carbon. Embodiment 343. The process of any one of embodiments 40 to 342, wherein hydrogenating the compound of Formula P, or a salt thereof, comprises contacting the compound of Formula P, or a salt thereof, with hydrogen.Attorney Docket No.: TGO-027WO Embodiment 344. The process of any one of embodiments 40 to 342, wherein hydrogenating the compound of Formula P, or a salt thereof, comprises contacting the compound of Formula P, or a salt thereof, with hydrogen at a pressure of at least about 2 MPa (e.g., between about 2 MPa and about 3 MPa). Embodiment 345. The process of any one of embodiments 40 to 344, wherein hydrogenating the compound of Formula P, or a salt thereof, comprises contacting the compound of Formula P, or a salt thereof, with a seventeenth solvent. Embodiment 346. The process of embodiment 345, wherein the seventeenth solvent is a protic solvent. Embodiment 347. The process of embodiment 345, wherein the seventeenth solvent is methanol (MeOH). Embodiment 348. The process of any one of embodiments 40 to 347, wherein hydrogenating the compound of Formula P, or a salt thereof, comprises elevating reaction temperature to higher than 40 °C. Embodiment 349. The process of any one of embodiments 40 to 347, wherein hydrogenating the compound of Formula P, or a salt thereof, comprises elevating reaction temperature to about 40 °C to about 60 °C. Embodiment 350. The process of any one of embodiments 40 to 347, wherein hydrogenating the compound of Formula P, or a salt thereof, comprises elevating reaction temperature to about 50 °C. Embodiment 351. The process of any one of embodiments 40 to 350, wherein oxalylamide installation on a compound of Formula P, or a salt thereof, comprisescontacting the compound of Formula P with wherein R12is C1-C6alkyl. Embodiment 352. The process of any one of embodiments 40 to 351, wherein oxalylamide installation on a compound of Formula P, or a salt thereof, comprisescontacting the compound of Formula P with . Embodiment 353. The process of any one of embodiments 40 to 352, wherein oxalylamide installation on a compound of Formula P, or a salt thereof, comprises contacting the compound of Formula P with a tenth base.Attorney Docket No.: TGO-027WO Embodiment 354. The process of embodiment 353, wherein the tenth base is an organic base. Embodiment 355. The process of embodiment 353, wherein the tenth base is an amine base (e.g., triethylamine (TEA), diisopropylethylamine (DIPEA), 4-dimethylamino pyridine (DMAP). Embodiment 356. The process of embodiment 353, wherein the tenth base is triethylamine (TEA). Embodiment 357. The process of any one of embodiments 40 to 356, wherein oxalylamide installation on a compound of Formula P, or a salt thereof, comprises contacting the compound of Formula P with an eighteenth solvent. Embodiment 358. The process of embodiment 357, wherein the eighteenth solvent is an organic solvent. Embodiment 359. The process of embodiment 357, wherein the nineteenth solvent is ethyl acetate (EtOAc). Embodiment 360. The process of any one of embodiments 40 to 359, wherein oxalylamide installation on a compound of Formula P, or a salt thereof comprises lowering the reaction temperature to between about 0 °C and about 10 °C. Embodiment 361. The process of any one of embodiments 40 to 360, wherein saponification of a compound of Formula R, or a salt thereof, comprises contacting the compound of Formula R with an eleventh base. Embodiment 362. The process of embodiment 361, wherein the eleventh base is an inorganic base. Embodiment 363. The process embodiment 361, wherein the eleventh base is a hydroxide base. Embodiment 364. The process of embodiment 361, wherein the eleventh base is LiOH. Embodiment 365. The process of any one of embodiments 40 to 364, wherein saponification of a compound of Formula R, or a salt thereof, comprises contacting the compound of Formula R with a nineteenth solvent. Embodiment 366. The process of embodiment 365, wherein the nineteenth solvent is a protic solvent. Embodiment 367. The process of embodiment 365, wherein the nineteenth solvent is ethanol (EtOH).Attorney Docket No.: TGO-027WO Embodiment 368. The process of any one of embodiments 40 to 367, wherein saponification of a compound of Formula R, or a salt thereof comprises lowering the reaction temperature to between about -10 °C and about 10 °C. Embodiment 369. The process of any one of embodiments 1 to 368, wherein R1is an optionally substituted oxazolidinone. Embodiment 370. The process of any one of embodiments 1 to 368, wherein R1is, wherein R10is C1-6alkyl, benzyl (Bn), or phenyl (Ph). Embodiment 371. The process of any one of embodiments 1 to 370, wherein R1is. Embodiment 372. The process of any one of embodiments 1 to 371, wherein R2is a carbamate group. Embodiment 373. The process of any one of embodiments 1 to 371, wherein R2is. Embodiment 374. The process of any one of embodiments 1 to 373, wherein R3is a boronic ester. Embodiment 375. The process of embodiment 374, wherein R3is , wherein each of R3aand R3bis, independently, H or C1-6alkyl, wherein R3aand R3bare optionally joined together with their intervening atoms to form a 5-10 membered ring that is optionally substituted with 0, 1, 2, 3, 4, 5, or 6 instances of wherein each R3cis, independently, C1-6alkyl. Embodiment 376. The process of embodiment 375, wherein each of R3aand R3bis, independently, C1-6 alkyl, wherein R3aand R3bare joined together with their intervening atoms to form a 5-10 membered ring that is optionally substituted with 0, 1, 2, 3, 4, 5, or 6 instances of R3c, wherein each R3cis, independently, C1-6alkyl.Attorney Docket No.: TGO-027WO Embodiment 377. The process of embodiment 375, wherein each of R3aand R3bis, independently, C1-6alkyl, wherein R3aand R3bare joined together r with their intervening atoms to form a 5-6 membered ring that is optionally substituted with 0, 1, 2, 3, 4, 5, or 6 instances of R3c, wherein each R3cis –Me. Embodiment 378. The process of embodiment 375, wherein R3is. Embodiment 379. The process of any one of embodiments 1 to 378, wherein R6is a carbamate. Embodiment 380. The process of embodiment 379, wherein R6is. Embodiment 381. The process of any one of embodiments 1 to 380, wherein R7is a carbamate. Embodiment 382. The process of any one of embodiments 1 to 381, wherein R7is. Embodiment 383. The process of any one of embodiments 1 to 382, wherein R8is a nitrogen protecting group and R9is a nitrogen protecting group. Embodiment 384. The process of any one of embodiments 1 to 382, wherein R8is a nitrogen protecting group and R9is H. Embodiment 385. The process of any one of embodiments 1 to 382, wherein R8is a carbamate group and R9is a carbamate group. Embodiment 386. The process of any one of embodiments 1 to 382, wherein R8is a carbamate group and R9is a H. Embodiment 387. The process of any one of embodiments 1 to 382, wherein R8isEmbodiment 389. The process of any one of embodiments 40 to 388, wherein R12is –Me, –Et, –nPr, –iPr, –nBu, or –tBu.Attorney Docket No.: TGO-027WO Embodiment 390. The process of any one of embodiments 40 to 388, wherein R12is –Et. Embodiment 391. A crystalline Form A of Compound A:. wherein Form A has an X-ray powder diffraction (XRPD) pattern comprising one or more peaks at 2θ angles selected from 11.6±0.2, 11.7±0.2, 14.5±0.2, 16.6±0.2, 17.2±0.2, 17.5±0.2, 17.6±0.2, 19±0.2, and 24.9±0.2. Embodiment 392. The crystalline Form A of Compound A of embodiment 391, wherein Form A has an X-ray powder diffraction (XRPD) pattern comprising 2θ angles of 11.6±0.2, 11.7±0.2, 14.5±0.2, 16.6±0.2, 17.2±0.2, 17.5±0.2, 17.6±0.2, 19±0.2, and 24.9±0.2. Embodiment 393. A crystalline Form B of Compound B:. wherein Form B has an X-ray powder diffraction (XRPD) pattern comprising one or more peaks at 2θ angles selected from 4.3±0.2, 8.6±0.2, 12.5±0.2, 15.5±0.2, 17±0.2, 17.6±0.2, 19.3±0.2, 21.4±0.2, 21.4±0.2, 23±0.2, 23.3±0.2, 24.5±0.2, and 27.3±0.2. Embodiment 394. The crystalline Form B of Compound B of embodiment 393, wherein Form B has an X-ray powder diffraction (XRPD) pattern comprising 2θ angles of 4.3±0.2, 8.6±0.2, 12.5±0.2, 15.5±0.2, 17±0.2, 17.6±0.2, 19.3±0.2, 21.4±0.2, 21.4±0.2, 23±0.2, 23.3±0.2, 24.5±0.2, and 27.3±0.2. EXAMPLE

[0298] In order that the invention described herein may be more fully understood, thefollowing example is set forth, which is not to be construed in any way as limiting the scope of the invention. AbbreviationsAttorney Docket No.: TGO-027WO AcOH Acetic acid API active pharmaceutical ingredient CSTR Continuous stirred tank reactor DCE dichloroethane DCM dichloromethane DMA N,N-dimethylacetamide DMAP dimethylaminopyridine EA ethyl acetate ee enantiomeric excess HPLC high performance liquid chromatography IPC In-process control IPA isopropyl alcohol MeCN acetonitrile n-BuLi n-Butyllithium NA not applicable NADP nicotinamide adenine dinucleotide phosphate NMP N-methyl-2-pyrrolidone PIV-Cl Pivaloyl chloride PFR Plug flow reactor RT room temperature or real time SD Standard Deviation TEA triethylamine TEOA-HCl triethanolamine hydrochloric acid TFA Trifluoroacetic acid THF tetrahydrofuran w / w weight-to-weight XRPD X-ray powder diffraction Part 1. Synthesis of tert-butyl (S)-5-methyl-2-oxopiperidine-1-carboxylate (INT- 3) using Hydrogenation with a Chiral AuxiliaryAttorney Docket No.: TGO-027WO 1,10 phenanthroline (246.2 g, 1.37 mol, 0.05 eq) were charged to a 50 L reactor then degassed with N2three times. CuI (259.8 g, 1.37 mol, 0.05 eq) was then charged to the reactor, then degassed with N2three times. The mixture was then heated to 140 °C and stirred for 5 h to completion as shown by HPLC. The mixture was then cooled to 20-30 °C, then filtered through diatomite and washed with NMP (9.4 L, 2 v). The filtrate was combined and then added gradually to water (47 liters, 10 volumes) while maintaining the temperature between 15-25 °C, followed by stirring for a duration of 1-2 h. The cake was then dissolved with EA (6 v) and washed with 5% NH3•H2O (14.1 L, 3 v), then washed again with H2O (14.1 L, 3 v). The organic layer was reduced in volume to approximately 2 volumes (9.8 liters) at a temperature of 40- 50 °C. Then, n-heptane (37.6 liters, 8 volumes) was added to the reduced concentrate, and the mixture was further concentrated to 5 volumes (23.5 liters) while maintaining the temperature at 40-50 °C. The mixture was then stirred for 2 h at a temperature range of 15-25 °C. After stirring, the mixture was filtered, and the resulting cake was washed with n-heptane (4.7 liters, 1 volume). The cake was then dried at a temperature of 40-50 °C for a period of 12-24 h, producing (S)-4-benzyl-3-(5-methylpyridin-2-yl)oxazolidin-2-one (INT-0) (6731 g, 87% yield).

[0300] 1H NMR (400 MHz, Chloroform-d) δ 8.25-8.24 (q, 1H), 8.12-8.10 (d, J = 8.56 Hz 1H), 7.59-7.56 (m, 1H), 7.37-7.23 (m, 5H), 5.13-5.08 (m, 1H), 4.34-4.23 (m, 2H), 3.44-3.40 (m, 1H), 2.87-2.82 (m, 1H), 2.35 (s, 3H).

[0301] MS =269.0 [M+H]+. Step 2: Synthesis of (S)-5-methylpiperidin-2-one (INT-2) – Method A

[0302] A 20 L reactor was charged with (S)-4-benzyl-3-(5-methylpyridin-2-yl)oxazolidin-2- one (5900 g), THF (50 L), water (14.75L) and 37% hydrochloric acid (810 g). The mixture was stirred until dissolved, then filtered through a pad of the Celite™ to afford a clear solution. A 1.25 L micropacked bed reactor was confirmed to be clean and dry, then charged with PDC1051 (5 wt% Pd / C, 810.00 g, 1.7 mol%). The jacket temperature and preheater were set to 65 °C and the hydrogen pressure was set as 3.0 MPa the hydrogen flow rate was set to 1000 mL / min. Once the hydrogen flow stabilized, the charging pump was initiated, and the solution flow rate was set to 30.0 mL / minute to commence the reaction. Throughout the reaction, in- process controls (IPC) were conducted every 2-4 h to monitor for the presence of (S)-4-benzyl- 3-(5-methylpyridin-2-yl)oxazolidin-2-one. The reaction solution was subjected to additionalAttorney Docket No.: TGO-027WO hydrogenation until substantially no (S)-4-benzyl-3-(5-methylpyridin-2-yl)oxazolidin-2-one remained.

[0303] For the workup, 40% NaOH (2.6 kg) aq. was added to the reaction mixture at 5-15 °C and the pH was adjusted to 10. The mixture was then concentrated at a temperature of 40-50 °C to remove THF. The mixture was then stirred for 2 h at a temperature of 5-10 °C, filtered, and the filtrate was collected (weight: 18.1 kg). A 1 kg sample of the filtrate was reserved, and the remaining filtrate was further processed. The filtrate was extracted with 2-MeTHF (7.5 L, 1.35 v), and after separation, the bottom of aqueous phase was concentrated at a temperature of 50- 55 °C until no fraction remained. MeCN (9.7 L, 1.6 v) was then charged to the concentrate and stirred for 1 h at 15-25 °C. The mixture was then filtered, and the cake was washed with MeCN (1 L, 0.2 v). The filtrate was concentrated at a temperature of 40-50 °C until no fraction remained, yielding 1622 g (S)-5-methylpiperidin-2-one (yellow oil with 70% yield).

[0304] 1H NMR: (400 MHz, Chloroform-d) 7.42 (s, 1H), 3.20-3.17 (m, 1H), 2.93-2.76 (m, 1H), 2.31-2.22 (m, 2H), 1.82-1.70 (m, 2H), 1.39-1.33 (m, 1H), 0.91-0.89 (d, J = 6.6 Hz, 3H).

[0305] MS =114.1 [M+H]+. Step 2: Synthesis of (S)-5-methylpiperidin-2-one (INT-2) – Method B

[0306] To a Parr hydrogenation apparatus was charged (S)-4-benzyl-3-(5-methylpyridin-2- yl)oxazolidin-2-one (4.5 kg, 16.77 mol), 5% Pd / C (900 g, 0.42 mol), methylsulfonyl acid (1.98 kg, 20.12 mol), water (11.25 kg), and THF (40.05 kg). The apparatus was degassed and refilled with H2three times. then the H2pressure was then set to 2.5 MPa and the temperature was set to 65 °C then stirred for 15 h. The mixture was then cooled until HPLC showed reaction completion. The mixture was then filtered through Celite™ (0.9 kg), the cake was washed with THF (1 kg), and the filtrate pH was adjusted to 10 by adding a 40% NaOH aqueous solution. This solution was concentrated to about 11 L and cooled to 0 °C. The mixture was then filtered and washed three times with 2-methyltetrahydrofuran (2-MeTHF) (3.87 kg). The combined 2- MeTHF layers were washed with water (4.5 kg), and the two aqueous layers were combined and the 2-MeTHF layers were discarded. The combined aqueous layers were then washed with 2-MeTHF (3.87 kg) and separated. NaCl (4.5 kg) was added to the aqueous layer, stirred until dissolved, then washed three times with dichloromethane (DCM) (17.96 kg). The combined DCM layers were concentrated to 3.5 L and MeCN (3.56 kg) was added. The resulting mixture was then charged with n-heptane (3.06 kg), concentrated to 3.5 L, heated to 55 °C, then cooled to 0 °C. After stirring for 3 h, the suspension was filtered, and the cake was washed with n-Attorney Docket No.: TGO-027WO heptane (3.06 kg). The cake was then dried under N2 flow at 10 °C for 20 h to obtain (S)-5- methylpiperidin-2-one (Formula B) as an off white solid (1.37 kg, 72% yield, 95% ee). Step 3: Synthesis of tert-butyl (S)-5-methyl-2-oxopiperidine-1-carboxylate (INT-3)

[0307] (S)-5-methylpiperidin-2-one (1600 g, 14.14 mol, 1.0 equivalent, with a QNMR purityof 86.3%), DMAP (172.7 g, 1.41 mol, 0.1 equivalent) and acetonitrile (MeCN) (8 liters, 5 volumes) were charged to a reactor and heated to a temperature range of 40-50 °C. (Boc)2O (3703 g, 16.97 mol, 1.2 eq) was then introduced dropwise to the reactor. The mixture was stirred at the same temperature range for 2 h until the reaction was completed as confirmed using HPLC. The mixture was then concentrated at 40-50 °C until no fraction remained. Methyl tert-butyl ether (MTBE) (8 L, 5 v) was added to the concentrated mixture and stirred for 1 h. The mixture was then washed twice with 10% citric acid aq. (4800 g X2, 3 v) and once with 10% NaCl aq. (4800 g, 3 v). The organic phase was concentrated at 40-50 °C until no fraction remained, yielding 2560 g of a crude yellow oil. The oil was charged with methyl tert-butyl ether (MTBE) (7 L) and silica (2300 g, 200-300 mesh) in the reactor and stirred for 2 h, then filtered. The wet cake was washed with MTBE (2.3 L). The combined filtrate was then concentrated at a temperature of 40-50 °C until no solvent remained, yielding 2388 g crude as a light-yellow oil. The oil was then charged with n-heptane (7.2 L, 3 v) and stirred for 4 h at a temperature of -15 to -13 ºC, then filtered. The cake was dried under N2at 15-25 °C, giving 1791 g of tert-butyl (S)-5-methyl-2-oxopiperidine-1-carboxylate (INT-3) as an off-white solid (59.4% yield, purity by HPLC of 99.0%; and an enantiomeric excess (e.e.) of 98.6%, as determined using a Daicel CHIRALPAK AD-RH column (150 mm X 4.6 mm, 5 μm) at a wavelength of 220 nm.

[0308] 1H NMR: (400 MHz, Chloroform-d) δ 3.82-3.77 (m, 1H), 3.15-3.09 (m, 1H), 2.60-2.43(m, 2H), 2.00-1.85 (m, 2H), 1.51-1.43 (m, 10H), 1.05-1.04 (d, J = 6.6 Hz, 3H).

[0309] MS = 449.2 [2M+Na]+.Part 2. Synthesis of tert-butyl (S)-5-methyl-2-oxopiperidine-1-carboxylate (INT- 3) using Enzymatic AmidationAttorney Docket No.: TGO-027WO

[0310] A reaction vessel was charged with sodium tetraborate decahydrate (Na2B4O7·10H2O)(26.3 kg) and purified water (1147 kg). Isopropylamine (i-PrNH2) (93.8 kg) was then added, followed by 35% HCl (123 kg) over 4-6 h to achieve a pH of 10.2 at a temperature of 20-30 °C. Subsequently, pyridoxal phosphate (PLP 0.98 kg) and INT-1 (45.8 kg) were added to the mixture, which was stirred for 1 h at 20-30 °C. The enzymatic catalyst ATA-22403 (obtained from STA Pharmaceutical Hong Kong Limited) (0.95 kg) was then added, and the temperature of the reaction mixture was adjusted to 40-50 °C and maintained with stirring for 20 h. The progress of the reaction was monitored. Upon completion, the temperature of the reaction mixture was adjusted to 20-30 °C, and zinc chloride (ZnCl2) (9.2 kg) was added. The mixture was then stirred for 1 h at 20-30 °C. The solution was then filtered with diatomite (30 kg), and the wet cake was rinsed twice with purified water (90 kg). The solution was then concentrated to 15-20 V under vacuum at a temperature below 45-55 °C. Sodium sulfate (Na2SO4) (50 kg) was then added, and the mixture was stirred for 1 h at a temperature of 20-30 °C. Dichloromethane (DCM) (601 kg) was then added. The solution was filtered through diatomite (25 kg), and the wet cake was rinsed with DCM (113 kg). After allowing the solution to stand for 1 h, the bottom layer was separated, and the upper layer was discarded. The upper layer was then washed four times with DCM (approximately 640 kg). The combined organic layers were then concentrated under vacuum to a volume of 180 L at a temperature below 50-60 °C. The resulting (S)-5-methylpiperidin-2-one (INT-2) (238.2 kg; after correcting for assay, 25.0 kg) was used in the following step. Step 2: Synthesis of tert-butyl (S)-5-methyl-2-oxopiperidine-1-carboxylate (INT-3)

[0311] (S)-5-methylpiperidin-2-one (INT-2) (25.0 kg) from the previous step was reduced to avolume of 50 L under vacuum at 45 °C. Dichloromethane (DCM) (136 kg) was then added, followed by n-heptane (135 kg), and the temperature of the reaction mixture was adjusted toAttorney Docket No.: TGO-027WO 20-30 °C. Subsequently, dimethylaminopyridine (DMAP) (5.4 kg) and triethylamine (TEA) (22.4 kg) were added. Di-tert-butyl decarbonate (Boc2O) (96.5 kg) was added dropwise over 4 h, and the resulting reaction mixture was stirred for 16 h at 20-30 °C. An additional amount of Boc2O (7.4 kg) was added dropwise over 2 h, and the mixture was stirred for another 5 h at 20- 30 °C. The reaction progress was monitored. Upon completion, 10% citric acid (130 kg) was added at a temperature of 15-25 °C, and the resulting mixture was stirred for 0.5-1 h. The mixture was then allowed to stand for 0.5-1 h. The following steps were performed twice: After separating the organic and aqueous layers, 10% citric acid (128 kg) was added to the aqueous layer at a temperature of 15-25 °C, and the resulting mixture was stirred for 0.5-1 h at the same temperature range, then allowed to stand for another 0.5-1 h. The organic layers were then combined and 7% NaHCO3(129 kg) was added at a temperature of 15-25 °C. The resulting mixture was stirred for 0.5-1 h at the same temperature range. The mixture was then allowed to stand for 0.5-1 h. The organic layer was then washed with 5% Na2SO4 (126 kg) at 15-25 °C and stirred at 15-25 °C for 0.5-1 h. After allowing the mixture to stand for 0.5-1 h, the layers were separated. The aqueous phase was then extracted with dichloromethane (DCM) (171 kg) at 15-25 °C, stirred for 0.5-1 h then allowed to stand for another 0.5-1 h at 15-25 °C. The organic layers were combined to obtain a solution of tert-butyl (S)-5-methyl-2-oxopiperidine- 1-carboxylate (INT-3; 420.6, kg). Step 3: Purification of tert-butyl (S)-5-methyl-2-oxopiperidine-1-carboxylate (INT-3)

[0312] 38.0 kg of the product from the previous step (INT-3) was charged to a reaction vessel.The organic layer was filtered using a CUNO™ filter at a temperature range of 20-30 °C for 2-4 h. The CUNO™ filter was then washed twice with DCM (183 kg). The solution was then concentrated to 2-3 vol. under vacuum at a temperature below 50 °C, then charged with n- heptane (100 kg). This step was repeated with another 100 kg of n-heptane, then again with 70 kg n-heptane. The temperature was then adjusted to 5-10 °C and the mixture was seeded with INT-3 (70 g). The temperature was then adjusted to -55 to -45 °C and stirred for 3 h. The product was filtered, and the cake was washed with 25 kg n-heptane. The wet cake was then dried at 20-30 °C for 20 h, resulting in INT-3 (97.8% enantiomeric excess, 99.9% purity, and 98.9%, containing less than 200 ppm DCM, 580 ppm n-heptane, and 0.1% KF).Attorney Docket No.: TGO-027WO Part 3. Synthesis of 2-(1-methylpiperidin-4-yl)-5-(4,4,5,5-tetramethyl-1,3,2-Step 1: Synthesis of 5-chloro-2-(1-methylpiperidin-4-yl)benzo[d]thiazole (INT-6)

[0313] A reactor was charged with polyphosphoric acid (PPA; 166 kg, 1.48 kmol, 166 L, 85%purity, 2.85 eq) and sulfolane (166 L). The mixture was heated to 105 ℃.1-methylpiperidine- 4-carboxylic acid (INT-5; 81.8 kg, 571 mol, 1.10 eq) was then added to the mixture, followed by the addition of 2-amino-4-chlorobenzenethiol (INT-4; 83.0 kg, 519 mol, 1.00 eq). The mixture was then stirred under N2for 12 h at 105 °C and monitored. After completion, the mixture was poured into H2O (200 L), and the pH adjusted to 9-10 with NaOH (20 wt % solution). The crude product was dissolved with MTBE (3.00 V) and washed with H2O (3.00 V). The organic phase was filtered, then gradient cooled to about -10 to -15 °C. The suspended solid was centrifuged and washed with MTBE (1.00 V). The product was then dried using a double cone dryer at 45-55oC to afford 5-chloro-2-(1-methylpiperidin-4-yl)benzo[d]thiazole (INT-6; 103 kg, 386 mol, 74.2% yield, 100% purity).

[0314] 1H NMR: 400 MHz, DMSO-d6 δ ppm 8.10 (d, J = 8.51 Hz, 1H) 8.03 (d, J = 2.00 Hz,1H) 7.46 (dd, J = 8.50, 2.00 Hz, 1H) 3.06 (ddt, J = 11.4, 7.72, 3.75, 3.75 Hz, 1H) 2.79 - 2.88 (m, 2H) 2.18 (s, 3H) 1.96 - 2.10 (m, 4H) 1.72 - 1.86 (m, 2H).Attorney Docket No.: TGO-027WO Step 2: Synthesis of 2-(1-methylpiperidin-4-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-

[0315] Tetrahydrofuran (THF) (800 g, 9V) was added to a reaction vessel, then subjected threetimes to an atmospheric swap with nitrogen (N2) under a vacuum pressure ranging from -0.1 to -0.06 Pascal (Pa). The vessel was subsequently bubbled with N2for 60 to 90 minutes. The temperature was adjusted to 20-30 °C and 5-chloro-2-(1-methylpiperidin-4- yl)benzo[d]thiazole (INT-6; 100 g, 1.0 equiv.; KF = 0.2%) was then introduced. Potassium acetate (KOAc) (110 g, 3.0 equiv.) was then added, and the mixture was concentrated at 40- 50 °C under vacuum until the volume was reduced to 3-4 V. THF (6V) and bis(pinacolato)diboron (Pin2B2) (114 g, 1.2 equiv.) were then added and the mixture was again bubbled with N2for 60 to 90 minutes. The mixture was charged with palladium(II) acetate (Pd(OAc)2) (0.85 g, 0.01 equiv.), XPhos (3.6 g, 0.02 equiv.), and THF (100 g, 1V) and then bubbled with N2 for an additional 2 to 4 h. The temperature was then adjusted to 65-75 °C and the mixture was stirred for 10 to 16 h. The reaction mixture was filtered through Celatom™ (diatomaceous earth) (0.5X) and the wet cake was rinsed twice with THF (360 g, 4V). The organic layers were combined, and the organic layers decolored using a CUNO™ (5 wt%) filter at 20-30 °C for 2 to 4 h. The CUNO™ filter was rinsed twice with THF (400 g) for 2 to 3 h and the organic layers combined and concentrated at 40-50 °C under vacuum until the volume was reduced to 3-4 V. The mixture was seeded with INT-7 (0.2 g) and stirred for 1 to 3 h at 40-50 °C. Acetonitrile (ACN) (315 g) was then added and the mixture was stirred for 4 to 6 h. The mixture was concentrated at 40-50 °C under vacuum to a volume of 3-4 V. ACN (235 g) was added and the mixture was stirred for another 4 to 6 h, then concentrated at 40- 50 °C under vacuum to a volume of 3-4 V. ACN (235 g) was charged to the vessel and the temperature was adjusted to 15-25 °C for 2 to 3 h. The vessel was then charged with triethylamine (TEA) (70 g) over 2 h at 15-25 °C, and the pH adjusted to 9.12. The mixture was stirred for 1 to 3 h at 15-25 °C. The temperature was then adjusted to -5 to 5 °C over 2 h and the mixture stirred for 8 to 12 h in this temperature range. The mixture was filtered ...

Claims

Attorney Docket No.: TGO-027WO CLAIMS 1. A process for preparing a compound of Formula X:or a salt thereof, comprising: enzymatically amidating a compound of Formula A2: Formula A2,or a salt thereof, wherein R11is C1-C6alkyl, thereby producing a compound of Formula B:or a salt thereof; and converting the compound of Formula B, or a salt thereof, to the compound of Formula X.

2. A process for preparing a compound of Formula X:Attorney Docket No.: TGO-027WO comprising: reducing a compound of Formula F:or a salt thereof, thereby producing a compound of Formula G:or a salt thereof; and converting the compound of Formula G, or a salt thereof, to the compound of Formula X.

3. A process for preparing a compound of Formula X:or a salt thereof, comprising: enzymatically reducing a compound of Formula F:Attorney Docket No.: TGO-027WOor a salt thereof, thereby producing a compound of Formula G: Formula G,or a salt thereof; and converting the compound of Formula G, or a salt thereof, to the compound of Formula X.

4. A process for preparing a compound of Formula X:comprising: coupling a compound of Formula G:Attorney Docket No.: TGO-027WO Formula G,or a salt thereof, with a compound of Formula H: Formula H,or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, thereby producing a first salt of a compound of Formula I:or a salt thereof, wherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group; and converting the first salt of the compound of Formula I to the compound of Formula X.

5. A process for preparing a compound of Formula X:Attorney Docket No.: TGO-027WOcomprising: free-basing a second salt of a compound of Formula I:wherein each of R8and R9is H, thereby producing the compound of Formula X.

6. The process of any one of claims 1 to 5, wherein the process further comprises: pivalamide protecting a compound of Formula J: Formula J,or a salt thereof, thereby producing a compound of Formula K: Formula K,or a salt thereof; installing an acetyl group on a compound of Formula K:Attorney Docket No.: TGO-027WO Formula K,or a salt thereof, thereby producing a compound of Formula L:or a salt thereof; reducing the carbonyl and pivalamide deprotecting of a compound of Formula L: L,or a salt thereof, thereby producing a compound of Formula M: Formula M,or a salt thereof; nitrating a compound of Formula M: Formula M,or a salt thereof, thereby producing a compound of Formula N: Formula N,or a salt thereof; nitrogen protecting a compound of Formula N:Attorney Docket No.: TGO-027WO or a salt thereof, thereby producing a compound of Formula O: Formula O,or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, nitro reducing a compound of Formula O: Formula O,or a salt thereof, thereby producing a compound of Formula P: Formula P,or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, installing an oxalylamide on a compound of Formula P: Formula P,or a salt thereof, thereby producing a compound of Formula R:or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group and R12is C1-C6alkyl, saponifying a compound of Formula R:Attorney Docket No.: TGO-027WOor a salt thereof, thereby producing a compound of Formula H: Formula H,or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group; and converting the compound of Formula H, or a salt thereof, to the compound of Formula X.

7. A process for preparing a compound of Formula X:comprising: pivalamide protecting a compound of Formula J: Formula J,or a salt thereof, thereby producing a compound of Formula K:Attorney Docket No.: TGO-027WO Formula K,or a salt thereof; installing an acetyl group on a compound of Formula K: Formula K,or a salt thereof, thereby producing a compound of Formula L: Formula L,or a salt thereof; reducing the carbonyl and pivalamide deprotecting of a compound of Formula L: Formula L,or a salt thereof, thereby producing a compound of Formula M: Formula M,or a salt thereof; nitrating a compound of Formula M: Formula M,or a salt thereof, thereby producing a compound of Formula N:Attorney Docket No.: TGO-027WO or a salt thereof; nitrogen protecting a compound of Formula N: Formula N,or a salt thereof, thereby producing a compound of Formula O: Formula O,or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, nitro reducing a compound of Formula O: Formula O,or a salt thereof, thereby producing a compound of Formula P: Formula P,or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, installing an oxalylamide on a compound of Formula P: Formula P,or a salt thereof, thereby producing a compound of Formula R:Attorney Docket No.: TGO-027WO or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group and R12is C1-C6alkyl, saponifying a compound of Formula Ror a salt thereof, thereby producing a compound of Formula H: Formula H,or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group; and converting the compound of Formula H, or a salt thereof, to the compound of Formula X.

8. A process for preparing a compound of Formula X: Formula X,or a salt thereof, comprising: hydrogenating a compound of Formula A1: Formula A1,or a salt thereof, wherein R1is a chiral auxiliary;Attorney Docket No.: TGO-027WO thereby producing a compound of Formula B: Formula B,or a salt thereof; protecting the nitrogen of a compound of Formula B: Formula B,or a salt thereof, thereby producing a compound of Formula C: Formula C,or a salt thereof, wherein R2is a nitrogen protecting group; cross-coupling a compound of Formula C: Formula C,or a salt thereof, wherein R2is a nitrogen protecting group, with a compound of Formula D: Formula D,or a salt thereof, wherein R3is a boronic acid or a boronic ester, thereby producing a compound of Formula E: Formula E,or a salt thereof, wherein R2is a nitrogen protecting group; removing nitrogen protecting group from a compound of Formula E:Attorney Docket No.: TGO-027WO Formula E,or a salt thereof, wherein R2is a nitrogen protecting group, thereby producing a compound of Formula F:or a salt thereof; reducing a compound of Formula F: Formula F,or a salt thereof, thereby producing a compound of Formula G: Formula G,or a salt thereof; coupling a compound of Formula G:Attorney Docket No.: TGO-027WO Formula G,or a salt thereof, with a compound of Formula H: Formula H,or a salt thereof, thereby producing a first salt of a compound of Formula I:wherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group; and removing one or more nitrogen protecting groups from a first salt of a compound of Formula I:Attorney Docket No.: TGO-027WOwherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group, thereby producing a second salt of a compound of Formula I:wherein each of R8and R9is H; and free-basing a second salt of a compound of Formula I:wherein each of R8and R9is H, thereby producing the compound of Formula X:Attorney Docket No.: TGO-027WO9. A process for preparing a compound of Formula X: Formula X,or a salt thereof, comprising: hydrogenating a compound of Formula A1: Formula A1,or a salt thereof, thereby producing a compound of Formula B: Formula B,or a salt thereof; protecting the nitrogen of a compound of Formula B: Formula B,or a salt thereof, thereby producing a compound of Formula C:Attorney Docket No.: TGO-027WO Formula C,or a salt thereof, wherein R2is a nitrogen protecting group; cross-coupling a compound of Formula C: Formula C,or a salt thereof, wherein R2is a nitrogen protecting group, with a compound of Formula D: Formula D,or a salt thereof, wherein R3is a boronic acid or a boronic ester, thereby producing a compound of Formula E: Formula E,or a salt thereof, wherein R2is a nitrogen protecting group; removing nitrogen protecting group from a compound of Formula E: Formula E,or a salt thereof, wherein R2is a nitrogen protecting group, thereby producing a compound of Formula F:Attorney Docket No.: TGO-027WOor a salt thereof; enzymatically reducing a compound of Formula F:or a salt thereof, thereby producing a compound of Formula G: Formula G,or a salt thereof; coupling a compound of Formula G: Formula G,or a salt thereof, with a compound of Formula H:Attorney Docket No.: TGO-027WO Formula H,or a salt thereof, thereby producing a first salt of a compound of Formula I:wherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group; and removing one or more nitrogen protecting groups from a first salt of a compound of Formula I:wherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group, thereby producing a second salt of a compound of Formula I:Attorney Docket No.: TGO-027WOwherein each of R8and R9is H; and free-basing a second salt of a compound of Formula I:wherein each of R8and R9is H, thereby producing the compound of Formula X:

10. A process for preparing a compound of Formula X:Attorney Docket No.: TGO-027WOor a salt thereof, comprising: enzymatically amidating a compound of Formula A2: Formula A2,or a salt thereof, wherein R11is C1-C6alkyl, thereby producing a compound of Formula B: Formula B,or a salt thereof; protecting the nitrogen of a compound of Formula B: Formula B,or a salt thereof, thereby producing a compound of Formula C: Formula C,or a salt thereof, wherein R2is a nitrogen protecting group; cross-coupling a compound of Formula C: Formula C, or a salt thereof, wherein R2is a nitrogen protecting group,Attorney Docket No.: TGO-027WO with a compound of Formula D: Formula D,or a salt thereof, wherein R3is a boronic acid or a boronic ester, thereby producing a compound of Formula E: Formula E,or a salt thereof, wherein R2is a nitrogen protecting group; removing nitrogen protecting group from a compound of Formula E:or a salt thereof, wherein R2is a nitrogen protecting group, thereby producing a compound of Formula F:or a salt thereof; reducing a compound of Formula F:Attorney Docket No.: TGO-027WOor a salt thereof, thereby producing a compound of Formula G:or a salt thereof; coupling a compound of Formula G: Formula G,or a salt thereof, with a compound of Formula H: Formula H,or a salt thereof, thereby producing a first salt of a compound of Formula I:Attorney Docket No.: TGO-027WOwherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group; and removing one or more nitrogen protecting groups from a first salt of a compound of Formula I:wherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group, thereby producing a second salt of a compound of Formula I:wherein each of R8and R9is H; andAttorney Docket No.: TGO-027WO free-basing a second salt of a compound of Formula I:wherein each of R8and R9is H, thereby producing the compound of Formula X:

11. A process for preparing a compound of Formula X:or a salt thereof, comprising: enzymatically amidating a compound of Formula A2:Attorney Docket No.: TGO-027WO Formula A2,or a salt thereof, thereby producing a compound of Formula B: Formula B,or a salt thereof; protecting the nitrogen of a compound of Formula B: Formula B,or a salt thereof, thereby producing a compound of Formula C: Formula C,or a salt thereof, wherein R2is a nitrogen protecting group; cross-coupling a compound of Formula C: Formula C,or a salt thereof, wherein R2is a nitrogen protecting group, with a compound of Formula D: Formula D,or a salt thereof, wherein R3is a boronic acid or a boronic ester, thereby producing a compound of Formula E:Attorney Docket No.: TGO-027WO Formula E,or a salt thereof, wherein R2is a nitrogen protecting group; removing nitrogen protecting group from a compound of Formula E:or a salt thereof, wherein R2is a nitrogen protecting group, thereby producing a compound of Formula F: Formula F,or a salt thereof; enzymatically reducing a compound of Formula F: Formula F,or a salt thereof, thereby producing a compound of Formula G:Attorney Docket No.: TGO-027WO Formula G,or a salt thereof; coupling a compound of Formula G: Formula G,or a salt thereof, with a compound of Formula H: Formula H,or a salt thereof, thereby producing a first salt of a compound of Formula I:wherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group; andAttorney Docket No.: TGO-027WO removing one or more nitrogen protecting groups from a first salt of a compound of Formula I:wherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group, thereby producing a second salt of a compound of Formula I:wherein each of R8and R9is H; and free-basing a second salt of a compound of Formula I:Attorney Docket No.: TGO-027WO thereby producing the compound of Formula X:

12. A process for preparing a compound of Formula X:comprising: hydrogenating a compound of Formula A1: Formula A1, or a salt thereof, wherein R1is a chiral auxiliary,thereby producing a compound of Formula B: Formula B, or a salt thereof;protecting the nitrogen of a compound of Formula B: Formula B, or a salt thereof,thereby producing a compound of Formula C:Attorney Docket No.: TGO-027WO Formula C, or a salt thereof2, wherein R is a nitrogen protecting group; cross-coupling a compound of Formula C: Formula C, or a salt thereof, with a compound of Formula D: Formula D,or a salt thereof, wherein R3is a boronic acid or a boronic ester, thereby producing a compound of Formula E: Formula E,or a salt thereof; removing nitrogen protecting group from a compound of Formula E: Formula E,or a salt thereof, thereby producing a compound of Formula F:Attorney Docket No.: TGO-027WO Formula F,or a salt thereof; reducing a compound of Formula F: Formula F,or a salt thereof, thereby producing a compound of Formula G:or a salt thereof; pivalamide protecting a compound of Formula J: Formula J,or a salt thereof, thereby producing a compound of Formula K: Formula K,or a salt thereof; installing an acetyl group on a compound of Formula K:Attorney Docket No.: TGO-027WO Formula K,or a salt thereof, thereby producing a compound of Formula L:or a salt thereof; reducing the carbonyl and pivalamide deprotecting of a compound of Formula L: L,or a salt thereof, thereby producing a compound of Formula M: Formula M,or a salt thereof; nitrating a compound of Formula M: Formula M,or a salt thereof, thereby producing a compound of Formula N: Formula N,or a salt thereof; nitrogen protecting a compound of Formula N:Attorney Docket No.: TGO-027WO or a salt thereof, thereby producing a compound of Formula O: Formula O,or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, nitro reducing a compound of Formula O: Formula O,or a salt thereof, thereby producing a compound of Formula P: Formula P,or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, installing an oxalylamide on a compound of Formula P: Formula P,or a salt thereof, thereby producing a compound of Formula R:or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group and R12is C1-C6alkyl, saponifying a compound of Formula R:Attorney Docket No.: TGO-027WOor a salt thereof, thereby producing a compound of Formula H: Formula H,or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, coupling a compound of Formula G: Formula G,or a salt thereof, with a compound of Formula H: Formula H,or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, thereby producing a first salt of a compound of Formula I:Attorney Docket No.: TGO-027WOremoving the nitrogen protecting groups from the first salt of a compound of Formula I:with a pharmaceutically acceptable acid, thereby producing a second salt of a compound of Formula I:and free-basing a second salt of a compound of Formula I:Attorney Docket No.: TGO-027WOthereby producing the compound of Formula X.

13. A process for preparing a compound of Formula X:comprising: hydrogenating a compound of Formula A1: Formula A1,or a salt thereof, wherein R1is a chiral auxiliary, thereby producing a compound of Formula B: Formula B,or a salt thereof; protecting the nitrogen of a compound of Formula B:Attorney Docket No.: TGO-027WO thereby producing a compound of Formula C: Formula C,or a salt thereof, wherein R2is a nitrogen protecting group; cross-coupling a compound of Formula C: Formula C,or a salt thereof, wherein R2is a nitrogen protecting group, with a compound of Formula D: Formula D,or a salt thereof, R3is a boronic acid or a boronic ester, thereby producing a compound of Formula E: Formula E,or a salt thereof, wherein R2is a nitrogen protecting group; removing nitrogen protecting group from a compound of Formula E:or a salt thereof, wherein R2is a nitrogen protecting group, thereby producing a compound of Formula F:Attorney Docket No.: TGO-027WO Formula F,or a salt thereof; enzymatically reducing a compound of Formula F: Formula F,or a salt thereof, thereby producing a compound of Formula G:or a salt thereof; pivalamide protecting a compound of Formula J: Formula J,or a salt thereof, thereby producing a compound of Formula K: Formula K,or a salt thereof; installing an acetyl group on a compound of Formula K:Attorney Docket No.: TGO-027WO Formula K,or a salt thereof, thereby producing a compound of Formula L:or a salt thereof; reducing the carbonyl and pivalamide deprotecting of a compound of Formula L: L,or a salt thereof, thereby producing a compound of Formula M: Formula M,or a salt thereof; nitrating a compound of Formula M: Formula M,or a salt thereof, thereby producing a compound of Formula N: Formula N,or a salt thereof; nitrogen protecting a compound of Formula N:Attorney Docket No.: TGO-027WO or a salt thereof, thereby producing a compound of Formula O: Formula O,or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, nitro reducing a compound of Formula O: Formula O,or a salt thereof, thereby producing a compound of Formula P: Formula P,or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, installing an oxalylamide on a compound of Formula P: Formula P,or a salt thereof, thereby producing a compound of Formula R:or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group and R12is C1-C6alkyl, saponifying a compound of Formula R:Attorney Docket No.: TGO-027WOor a salt thereof, thereby producing a compound of Formula H:or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, coupling a compound of Formula G: Formula G,or a salt thereof, with a compound of Formula H: Formula H,or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, thereby producing a first salt of a compound of Formula I:Attorney Docket No.: TGO-027WOR7; removing the nitrogen protecting groups from a first salt of a compound of Formulawith a pharmaceutically acceptable acid, thereby producing a second salt of a compound of Formula I:H; and free-basing a second salt of a compound of Formula I:Attorney Docket No.: TGO-027WOthereby producing the compound of Formula X.

14. A process for preparing a compound of Formula X:or a salt thereof, comprising: enzymatically amidating a compound of Formula A2: Formula A2,or a salt thereof, wherein R11is C1-C6alkyl, thereby producing a compound of Formula B: Formula B,or a salt thereof; protecting the nitrogen of a compound of Formula B:Attorney Docket No.: TGO-027WO or a salt thereof, thereby producing a compound of Formula C: Formula C, or a salt thereof, wherein R2is a nitrogen protecting group; cross-coupling a compound of Formula C: Formula C,or a salt thereof, wherein R2is a nitrogen protecting group, with a compound of Formula D: Formula D,or a salt thereof, wherein R3is a boronic acid or a boronic ester, thereby producing a compound of Formula E: Formula E,or a salt thereof, wherein R2is a nitrogen protecting group; removing nitrogen protecting group from a compound of Formula E: Formula E,or a salt thereof, wherein R2is a nitrogen protecting group, thereby producing a compound of Formula F:Attorney Docket No.: TGO-027WO Formula F,or a salt thereof; reducing a compound of Formula F: Formula F,or a salt thereof, thereby producing a compound of Formula G:or a salt thereof; pivalamide protecting a compound of Formula J: Formula J,or a salt thereof, thereby producing a compound of Formula K: Formula K,or a salt thereof; installing an acetyl group on a compound of Formula K:Attorney Docket No.: TGO-027WO Formula K,or a salt thereof, thereby producing a compound of Formula L:or a salt thereof; reducing the carbonyl and pivalamide deprotecting of a compound of Formula L: L,or a salt thereof, thereby producing a compound of Formula M: Formula M,or a salt thereof; nitrating a compound of Formula M: Formula M,or a salt thereof, thereby producing a compound of Formula N: Formula N,or a salt thereof; nitrogen protecting a compound of Formula N:Attorney Docket No.: TGO-027WO or a salt thereof, thereby producing a compound of Formula O: Formula O,or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, nitro reducing a compound of Formula O: Formula O,or a salt thereof, thereby producing a compound of Formula P: Formula P,or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, installing an oxalylamide on a compound of Formula P: Formula P,or a salt thereof, thereby producing a compound of Formula R:or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group and R12is C1-C6alkyl, saponifying a compound of Formula R:Attorney Docket No.: TGO-027WOor a salt thereof, thereby producing a compound of Formula H:or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, coupling a compound of Formula G: Formula G,or a salt thereof, with a compound of Formula H: Formula H,or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, thereby producing a first salt of a compound of Formula I:Attorney Docket No.: TGO-027WOremoving the nitrogen protecting groups from the first salt of a compound of Formula I:with a pharmaceutically acceptable acid, thereby producing a second salt of a compound of Formula I:and free-basing a second salt of a compound of Formula I:Attorney Docket No.: TGO-027WOthereby producing the compound of Formula X.

15. A process for preparing a compound of Formula X:comprising: enzymatically amidating a compound of Formula A2: Formula A2,or a salt thereof, wherein R11is C1-C6alkyl, thereby producing a compound of Formula B: Formula B,or a salt thereof; protecting the nitrogen of a compound of Formula B:Attorney Docket No.: TGO-027WO or a salt thereof, thereby producing a compound of Formula C: Formula C, or a salt thereof; cross-coupling a compound of Formula C: Formula C,or a salt thereof, wherein R2is a nitrogen protecting group, with a compound of Formula D: Formula D,or a salt thereof, wherein R3is a boronic acid or a boronic ester, thereby producing a compound of Formula E: Formula E,or a salt thereof, wherein R2is a nitrogen protecting group; removing nitrogen protecting group from a compound of Formula E: Formula E,or a salt thereof, wherein R2is a nitrogen protecting group, thereby producing a compound of Formula F:Attorney Docket No.: TGO-027WO Formula F,or a salt thereof; enzymatically reducing a compound of Formula F: Formula F,or a salt thereof, thereby producing a compound of Formula G:or a salt thereof; pivalamide protecting a compound of Formula J: Formula J,or a salt thereof, thereby producing a compound of Formula K: Formula K,or a salt thereof; installing an acetyl group on a compound of Formula K:Attorney Docket No.: TGO-027WO Formula K,or a salt thereof, thereby producing a compound of Formula L:or a salt thereof; reducing the carbonyl and pivalamide deprotecting of a compound of Formula L: L,or a salt thereof, thereby producing a compound of Formula M: Formula M,or a salt thereof; nitrating a compound of Formula M: Formula M,or a salt thereof, thereby producing a compound of Formula N: Formula N,or a salt thereof; nitrogen protecting a compound of Formula N:Attorney Docket No.: TGO-027WO or a salt thereof, thereby producing a compound of Formula O: Formula O,or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, nitro reducing a compound of Formula O: Formula O,or a salt thereof, thereby producing a compound of Formula P: Formula P,or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, installing an oxalylamide on a compound of Formula P: Formula P,or a salt thereof, thereby producing a compound of Formula R:or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group and R12is C1-C6alkyl, saponifying a compound of Formula R:Attorney Docket No.: TGO-027WOor a salt thereof, thereby producing a compound of Formula H:or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, coupling a compound of Formula G: Formula G,or a salt thereof, with a compound of Formula H: Formula H,or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, thereby producing a first salt of a compound of Formula I:Attorney Docket No.: TGO-027WOR7; removing the nitrogen protecting groups from a first salt of a compound of Formulathereby producing a second salt of a compound of Formula I:and free-basing a second salt of a compound of Formula I:Attorney Docket No.: TGO-027WOthereby producing the compound of Formula X.

16. A process for preparing a compound of Formula X:or a salt thereof, comprising: free-basing a second salt of a compound of Formula I:wherein each of R8and R9is H, wherein the second salt of the compound of Formula I is prepared by removing one or more nitrogen protecting groups from a first salt of a compound of Formula I:Attorney Docket No.: TGO-027WOwherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group, wherein the first salt of the compound of Formula I is prepared by coupling a compound of Formula G: Formula G,or a salt thereof, with a compound of Formula H: Formula H,or a salt thereof, wherein the compound of Formula G, or a salt thereof, is prepared by reducing a compound of Formula F:Attorney Docket No.: TGO-027WO or a salt thereof, wherein the compound of Formula F, or a salt thereof, is prepared by removing nitrogen protecting group from a compound of Formula E: Formula E,or a salt thereof, wherein R2is a nitrogen protecting group, wherein the compound of Formula E, or a salt thereof, is prepared by cross-coupling a compound of Formula C: Formula C,or a salt thereof, wherein R2is a nitrogen protecting group, with a compound of Formula D: Formula D,or a salt thereof, wherein R3is a boronic acid or a boronic ester, wherein the compound of Formula C, or a salt thereof, is prepared by protecting the nitrogen of a compound of Formula B: Formula B,or a salt thereof, wherein the compound of Formula B, or a salt thereof, is prepared by hydrogenating a compound of Formula A1: Formula A1,or a salt thereof, wherein R1is a chiral auxiliary.

17. A process for preparing a compound of Formula X:Attorney Docket No.: TGO-027WOor a salt thereof, comprising: free-basing a second salt of a compound of Formula I:wherein each of R8and R9is H, wherein the second salt of the compound of Formula I is prepared by removing one or more nitrogen protecting groups from a first salt of a compound of Formula I:wherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group,Attorney Docket No.: TGO-027WO wherein the first salt of the compound of Formula I is prepared by coupling a compound of Formula G: Formula G,or a salt thereof, with a compound of Formula H: Formula H,or a salt thereof, wherein the compound of Formula G, or a salt thereof, is prepared by enzymatically reducing a compound of Formula F: Formula F,or a salt thereof, wherein the compound of Formula F, or a salt thereof, is prepared by removing nitrogen protecting group from a compound of Formula E: Formula E,or a salt thereof, wherein R2is a nitrogen protecting group,Attorney Docket No.: TGO-027WO wherein the compound of Formula E, or a salt thereof, is prepared by cross-coupling a compound of Formula C: Formula C, or a salt thereof, wherein R2is a nitrogen protecting group, with a compound of Formula D: Formula D,or a salt thereof, wherein R3is a boronic acid or a boronic ester, wherein the compound of Formula C, or a salt thereof, is prepared by protecting the nitrogen of a compound of Formula B: Formula B,or a salt thereof, wherein the compound of Formula B, or a salt thereof, is prepared by hydrogenating a compound of Formula A1: Formula A1,or a salt thereof, wherein R1is a chiral auxiliary.

18. A process for preparing a compound of Formula X: Formula X,or a salt thereof, comprising: free-basing a second salt of a compound of Formula I:Attorney Docket No.: TGO-027WOwherein each of R8and R9is H, wherein the second salt of the compound of Formula I is prepared by removing one or more nitrogen protecting groups from a first salt of a compound of Formula I:wherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group, wherein the first salt of the compound of Formula I is prepared by coupling a compound of Formula G:or a salt thereof, with a compound of Formula H:Attorney Docket No.: TGO-027WO Formula H,or a salt thereof, wherein the compound of Formula G, or a salt thereof, is prepared by reducing a compound of Formula F:or a salt thereof, wherein the compound of Formula F, or a salt thereof, is prepared by removing nitrogen protecting group from a compound of Formula E: Formula E,or a salt thereof, wherein R2is a nitrogen protecting group, wherein the compound of Formula E, or a salt thereof, is prepared by cross-coupling a compound of Formula C: Formula C,or a salt thereof, wherein R2is a nitrogen protecting group, with a compound of Formula D: Formula D,or a salt thereof, wherein R3is a boronic acid or a boronic ester,Attorney Docket No.: TGO-027WO wherein the compound of Formula C, or a salt thereof, is prepared by protecting the nitrogen of a compound of Formula B: Formula B,or a salt thereof, wherein the compound of Formula B, or a salt thereof, is prepared by enzymatically amidating a compound of Formula A2: Formula A2,or a salt thereof, wherein R11is C1-C6alkyl.

19. A process for preparing a compound of Formula X: Formula X,or a salt thereof, comprising: free-basing a second salt of a compound of Formula I:Attorney Docket No.: TGO-027WO wherein the second salt of the compound of Formula I is prepared by removing one or more nitrogen protecting groups from a first salt of a compound of Formula I:wherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group, wherein the first salt of the compound of Formula I is prepared by coupling a compound of Formula G: Formula G,or a salt thereof, with a compound of Formula H:or a salt thereof, wherein the compound of Formula G, or a salt thereof, is prepared by enzymatically reducing a compound of Formula F:Attorney Docket No.: TGO-027WO Formula F,or a salt thereof, wherein the compound of Formula F, or a salt thereof, is prepared by removing nitrogen protecting group from a compound of Formula E: Formula E,or a salt thereof, wherein R2is a nitrogen protecting group, wherein the compound of Formula E, or a salt thereof, is prepared by cross-coupling a compound of Formula C: Formula C,or a salt thereof, wherein R2is a nitrogen protecting group, with a compound of Formula D: Formula D,or a salt thereof, wherein R3is a boronic acid or a boronic ester, wherein the compound of Formula C, or a salt thereof, is prepared by protecting the nitrogen of a compound of Formula B: Formula B,or a salt thereof, wherein the compound of Formula B, or a salt thereof, is prepared by enzymatically amidating a compound of Formula A2:Attorney Docket No.: TGO-027WO Formula A2,or a salt thereof, wherein R11is C1-C6alkyl.

20. The process of any one of claims 16 to 19 wherein the compound of Formula H: Formula H,or a salt thereof, is prepared by saponifying a compound of Formula R:or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, wherein the compound of Formula R, or a salt thereof, is prepared by installing an oxalylamide on a compound of Formula P: Formula P,or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group and R12is C1-C6 alkyl, wherein the compound of Formula P, or a salt thereof, is prepared by nitro reducing a compound of Formula O: Formula O,or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, wherein the compound of Formula O, or a salt thereof, is prepared by nitrogen protecting a compound of Formula N,Attorney Docket No.: TGO-027WO Formula N,or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, wherein the compound of Formula N, or a salt thereof, is prepared by nitrating a compound of Formula M: Formula M,or a salt thereof, wherein the compound of Formula M, or a salt thereof is prepared by reducing the carbonyl and pivalamide deprotecting of a compound of Formula L: Formula L,or a salt thereof, wherein the compound of Formula L, or a salt thereof is prepared by installing an acetyl group on a compound of Formula K: Formula K,or a salt thereof, wherein the compound of Formula K, or a salt thereof is prepared by pivalamide protecting a compound of Formula J: Formula J,or a salt thereof.

21. A process for preparing a compound of Formula X:Attorney Docket No.: TGO-027WOor a salt thereof, comprising: free-basing a second salt of a compound of Formula I:wherein each of R8and R9is H, wherein the second salt of the compound of Formula I is prepared by removing one or more nitrogen protecting groups from a first salt of a compound of Formula I:wherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group,Attorney Docket No.: TGO-027WO wherein the first salt of the compound of Formula I is prepared by coupling a compound of Formula G: Formula G,or a salt thereof, with a compound of Formula H: Formula H,or a salt thereof, wherein the compound of Formula G, or a salt thereof, is prepared by reducing a compound of Formula F: Formula F,or a salt thereof, wherein the compound of Formula F, or a salt thereof, is prepared by removing nitrogen protecting group from a compound of Formula E: Formula E,or a salt thereof, wherein R2is a nitrogen protecting group,Attorney Docket No.: TGO-027WO wherein the compound of Formula E, or a salt thereof, is prepared by cross-coupling a compound of Formula C: Formula C,or a salt thereof, wherein R2is a nitrogen protecting group, with a compound of Formula D: Formula D,or a salt thereof, wherein R3is a boronic acid or a boronic ester, wherein the compound of Formula C, or a salt thereof, is prepared by protecting the nitrogen of a compound of Formula B: Formula B,or a salt thereof, wherein the compound of Formula B, or a salt thereof, is prepared by hydrogenating a compound of Formula A1: Formula A1,or a salt thereof, wherein R1is a chiral auxiliary, wherein the compound of Formula H: Formula H,or a salt thereof, is prepared by saponifying a compound of Formula R:or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group,Attorney Docket No.: TGO-027WO wherein the compound of Formula R, or a salt thereof, is prepared by installing an oxalylamide on a compound of Formula P: Formula P,or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group and R12is C1-C6alkyl, wherein the compound of Formula P, or a salt thereof, is prepared by nitro reducing a compound of Formula O: Formula O,or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, wherein the compound of Formula O, or a salt thereof, is prepared by nitrogen protecting a compound of Formula N, Formula N,or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, wherein the compound of Formula N, or a salt thereof, is prepared by nitrating a compound of Formula M: Formula M,or a salt thereof, wherein the compound of Formula M, or a salt thereof is prepared by reducing the carbonyl and pivalamide deprotecting of a compound of Formula L:Attorney Docket No.: TGO-027WO wherein the compound of Formula L, or a salt thereof is prepared by installing an acetyl group on a compound of Formula K: Formula K, or a salt thereof, wherein the compound of Formula K, or a salt thereof is prepared by pivalamide protecting a compound of Formula J: Formula J,or a salt thereof.

22. A process for preparing a compound of Formula X:or a salt thereof, comprising: free-basing a second salt of a compound of Formula I:Attorney Docket No.: TGO-027WO wherein the second salt of the compound of Formula I is prepared by removing one or more nitrogen protecting groups from a first salt of a compound of Formula I:wherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group, wherein the first salt of the compound of Formula I is prepared by coupling a compound of Formula G: Formula G,or a salt thereof, with a compound of Formula H:or a salt thereof, wherein the compound of Formula G, or a salt thereof, is prepared by enzymatically reducing a compound of Formula F:Attorney Docket No.: TGO-027WO Formula F,or a salt thereof, wherein the compound of Formula F, or a salt thereof, is prepared by removing nitrogen protecting group from a compound of Formula E: Formula E,or a salt thereof, wherein R2is a nitrogen protecting group, wherein the compound of Formula E, or a salt thereof, is prepared by cross-coupling a compound of Formula C: Formula C,or a salt thereof, wherein R2is a nitrogen protecting group, with a compound of Formula D: Formula D,or a salt thereof, wherein R3is a boronic acid or a boronic ester, wherein the compound of Formula C, or a salt thereof, is prepared by protecting the nitrogen of a compound of Formula B: Formula B,or a salt thereof, wherein the compound of Formula B, or a salt thereof, is prepared by hydrogenating a compound of Formula A1:Attorney Docket No.: TGO-027WO Formula A1,or a salt thereof, wherein R1is a chiral auxiliary, wherein the compound of Formula H: Formula H,or a salt thereof, is prepared by saponifying a compound of Formula R:or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, wherein the compound of Formula R, or a salt thereof, is prepared by installing an oxalylamide on a compound of Formula P: Formula P,or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group and R12is C1-C6alkyl, wherein the compound of Formula P, or a salt thereof, is prepared by nitro reducing a compound of Formula O: Formula O,or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, wherein the compound of Formula O, or a salt thereof, is prepared by nitrogen protecting a compound of Formula N,Attorney Docket No.: TGO-027WO or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, wherein the compound of Formula N, or a salt thereof, is prepared by nitrating a compound of Formula M: Formula M,or a salt thereof, wherein the compound of Formula M, or a salt thereof is prepared by reducing the carbonyl and pivalamide deprotecting of a compound of Formula L: Formula L,or a salt thereof, wherein the compound of Formula L, or a salt thereof is prepared by installing an acetyl group on a compound of Formula K: Formula K,or a salt thereof, wherein the compound of Formula K, or a salt thereof is prepared by pivalamide protecting a compound of Formula J: Formula J,or a salt thereof.

23. A process for preparing a compound of Formula X:Attorney Docket No.: TGO-027WOor a salt thereof, comprising: free-basing a second salt of a compound of Formula I:wherein each of R8and R9is H, wherein the second salt of the compound of Formula I is prepared by removing one or more nitrogen protecting groups from a first salt of a compound of Formula I:wherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group,Attorney Docket No.: TGO-027WO wherein the first salt of the compound of Formula I is prepared by coupling a compound of Formula G: Formula G,or a salt thereof, with a compound of Formula H: Formula H,or a salt thereof, wherein the compound of Formula G, or a salt thereof, is prepared by reducing a compound of Formula F: Formula F,or a salt thereof, wherein the compound of Formula F, or a salt thereof, is prepared by removing nitrogen protecting group from a compound of Formula E: Formula E,or a salt thereof, wherein R2is a nitrogen protecting group,Attorney Docket No.: TGO-027WO wherein the compound of Formula E, or a salt thereof, is prepared by cross-coupling a compound of Formula C: Formula C, or a salt thereof, wherein R2is a nitrogen protecting group, with a compound of Formula D: Formula D,or a salt thereof, wherein R3is a boronic acid or a boronic ester, wherein the compound of Formula C, or a salt thereof, is prepared by protecting the nitrogen of a compound of Formula B: Formula B,or a salt thereof, wherein the compound of Formula B, or a salt thereof, is prepared by enzymatically amidating a compound of Formula A2: Formula A2,or a salt thereof, wherein R11is C1-C6alkyl, wherein the compound of Formula H: Formula H,or a salt thereof, is prepared by saponifying a compound of Formula R:or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group,Attorney Docket No.: TGO-027WO wherein the compound of Formula R, or a salt thereof, is prepared by installing an oxalylamide on a compound of Formula P: Formula P,or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group and R12is C1-C6alkyl, wherein the compound of Formula P, or a salt thereof, is prepared by nitro reducing a compound of Formula O: Formula O,or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, wherein the compound of Formula O, or a salt thereof, is prepared by nitrogen protecting a compound of Formula N, Formula N,or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, wherein the compound of Formula N, or a salt thereof, is prepared by nitrating a compound of Formula M: Formula M,or a salt thereof, wherein the compound of Formula M, or a salt thereof is prepared by reducing the carbonyl and pivalamide deprotecting of a compound of Formula L:Attorney Docket No.: TGO-027WO wherein the compound of Formula L, or a salt thereof is prepared by installing an acetyl group on a compound of Formula K: Formula K, or a salt thereof, wherein the compound of Formula K, or a salt thereof is prepared by pivalamide protecting a compound of Formula J:or a salt thereof.

24. A process for preparing a compound of Formula X:or a salt thereof, comprising: free-basing a second salt of a compound of Formula I:Attorney Docket No.: TGO-027WO wherein the second salt of the compound of Formula I is prepared by removing one or more nitrogen protecting groups from a first salt of a compound of Formula I:wherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group, wherein the first salt of the compound of Formula I is prepared by coupling a compound of Formula G: Formula G,or a salt thereof, with a compound of Formula H:or a salt thereof, wherein the compound of Formula G, or a salt thereof, is prepared by enzymatically reducing a compound of Formula F:Attorney Docket No.: TGO-027WO Formula F,or a salt thereof, wherein the compound of Formula F, or a salt thereof, is prepared by removing nitrogen protecting group from a compound of Formula E: Formula E,or a salt thereof, wherein R2is a nitrogen protecting group, wherein the compound of Formula E, or a salt thereof, is prepared by cross-coupling a compound of Formula C: Formula C,or a salt thereof, wherein R2is a nitrogen protecting group, with a compound of Formula D: Formula D,or a salt thereof, wherein R3is a boronic acid or a boronic ester, wherein the compound of Formula C, or a salt thereof, is prepared by protecting the nitrogen of a compound of Formula B: Formula B,or a salt thereof, wherein the compound of Formula B, or a salt thereof, is prepared by enzymatically amidating a compound of Formula A2:Attorney Docket No.: TGO-027WO Formula A2,or a salt thereof, wherein R11is C1-C6alkyl, wherein the compound of Formula H: Formula H,or a salt thereof, is prepared by saponifying a compound of Formula R:or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, wherein the compound of Formula R, or a salt thereof, is prepared by installing an oxalylamide on a compound of Formula P: Formula P,or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group and R12is C1-C6 alkyl, wherein the compound of Formula P, or a salt thereof, is prepared by nitro reducing a compound of Formula O: Formula O,or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, wherein the compound of Formula O, or a salt thereof, is prepared by nitrogen protecting a compound of Formula N,Attorney Docket No.: TGO-027WO Formula N,or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, wherein the compound of Formula N, or a salt thereof, is prepared by nitrating a compound of Formula M: Formula M,or a salt thereof, wherein the compound of Formula M, or a salt thereof is prepared by reducing the carbonyl and pivalamide deprotecting of a compound of Formula L: Formula L,or a salt thereof, wherein the compound of Formula L, or a salt thereof is prepared by installing an acetyl group on a compound of Formula K: Formula K,or a salt thereof, wherein the compound of Formula K, or a salt thereof is prepared by pivalamide protecting a compound of Formula J: Formula J,or a salt thereof.

25. A process for preparing a compound of Formula P:Attorney Docket No.: TGO-027WO or a salt thereof, comprising: pivalamide protecting a compound of Formula J: Formula J,or a salt thereof, thereby producing a compound of Formula K: Formula K,or a salt thereof; installing an acetyl group on a compound of Formula K: Formula K,or a salt thereof, thereby producing a compound of Formula L: L,or a salt thereof; reducing the carbonyl and pivalamide deprotecting of a compound of Formula L: Formula L,or a salt thereof, thereby producing a compound of Formula M: Formula M,or a salt thereof; nitrating a compound of Formula M:Attorney Docket No.: TGO-027WO Formula M,or a salt thereof, thereby producing a compound of Formula N: Formula N,or a salt thereof; nitrogen protecting a compound of Formula N: Formula N,or a salt thereof, thereby producing a compound of Formula O: Formula O,or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group, nitro reducing a compound of Formula O: Formula O,or a salt thereof, thereby producing a compound of Formula P: Formula P,or a salt thereof; wherein R6and R7are each an independently selected nitrogen protecting group.

26. A process for preparing a compound of Formula P:Attorney Docket No.: TGO-027WO or a salt thereof, comprising: nitro reducing a compound of Formula O: Formula O,or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, wherein the compound of Formula O, or a salt thereof, is prepared by nitrogen protecting a compound of Formula N, Formula N,or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group, wherein the compound of Formula N, or a salt thereof, is prepared by nitrating a compound of Formula M: Formula M,or a salt thereof, wherein the compound of Formula M, or a salt thereof is prepared by reducing the carbonyl and pivalamide deprotecting of a compound of Formula L: L,or a salt thereof, wherein the compound of Formula L, or a salt thereof is prepared by installing an acetyl group on a compound of Formula K:Attorney Docket No.: TGO-027WO wherein the compound of Formula K, or a salt thereof is prepared by pivalamide protecting a compound of Formula J: Formula J,or a salt thereof.

27. A process for preparing a compound of Formula B: Formula B,or a salt thereof, comprising: enzymatically amidating a compound of Formula A2: Formula A2,or a salt thereof, wherein R11is C1-C6alkyl, thereby producing a compound of Formula B, or a salt thereof.

28. A process for preparing a compound of Formula G: Formula G,or a salt thereof, comprising: reducing a compound of Formula F:or a salt thereof, thereby producing a compound of Formula G, or a salt thereof.Attorney Docket No.: TGO-027WO 29. A process for preparing a compound of Formula G: Formula G,or a salt thereof, comprising: enzymatically reducing a compound of Formula F:or a salt thereof, thereby producing a compound of Formula G, or a salt thereof.

30. A process for preparing a first salt of a compound of Formula I:wherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group, comprising: coupling a compound of Formula G:Attorney Docket No.: TGO-027WO Formula G,or a salt thereof, with a compound of Formula H: Formula H,or a salt thereof, wherein R6and R7are each an independently selected nitrogen protecting group.

31. A process for preparing a second salt of a compound of Formula I:wherein each of R8and R9is H, comprising removing one or more nitrogen protecting groups from a first salt of a compound of Formula I:Attorney Docket No.: TGO-027WOwherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group.

32. The process of claim 30, wherein coupling of the compound of Formula G, or a salt thereof, with the compound of Formula H, or a salt thereof, produces a first salt of the compound of Formula I.

33. The process of claim 31, wherein the first salt of the compound of Formula I is: .

34. A process for preparing a compound of Formula X:comprising: removing one or more nitrogen protecting groups from a first salt of a compound of Formula I:Attorney Docket No.: TGO-027WOwherein each of R8and R9is, independently, H or a nitrogen protecting group and at least one of R8and R9is a nitrogen protecting group, thereby producing a second salt of a compound of Formula I,wherein each of R8and R9is H.

35. The process of any one of claims 1 to 34, wherein the first salt of the compound of Formula I is a crystalline form of the first salt of the compound of Formula I.

36. The process of claim 35, wherein the first salt of the compound of Formula I is a formic acid salt of the compound of Formula I.

37. The process of claim 35 or 36, wherein the first salt of the compound of Formula I is Compound A: .Attorney Docket No.: TGO-027WO 38. The process of claim 37, wherein Compound A is a crystalline Form A of Compound A.

39. The process of claim 38, wherein Form A has an X-ray powder diffraction (XRPD) pattern comprising one or more peaks at 2θ angles selected from 11.6±0.2, 11.7±0.2, 14.5±0.2, 16.6±0.2, 17.2±0.2, 17.5±0.2, 17.6±0.2, 19±0.2, and 24.9±0.

2.

40. The process of claim 38 or 39, wherein Form A has an X-ray powder diffraction (XRPD) pattern comprising 2θ angles of 11.6±0.2, 11.7±0.2, 14.5±0.2, 16.6±0.2, 17.2±0.2, 17.5±0.2, 17.6±0.2, 19±0.2, and 24.9±0.

2.

41. The process of any one of claims 1 to 40, wherein the second salt of the compound of Formula I is a crystalline form of the second salt of the compound of Formula I.

42. The process of claim 41, wherein the second salt of the compound of Formula I is selected from a phosphoric acid salt of the compound of Formula I, a sulfuric acid salt of the compound of Formula I, and a benzoic acid salt of the compound of Formula I.

43. The process of claim 41 or 42, wherein the second salt of the compound of Formula I is a formic acid salt of the compound of Formula I.

44. The process of any one of claims 41 to 43, wherein the second salt of the compound of Formula I is Compound B: .

45. The process of claim 44, wherein Compound B is a crystalline Form B of Compound B.

46. The process of claim 45, wherein Form B has an X-ray powder diffraction (XRPD) pattern comprising one or more peaks at 2θ angles selected from 4.3±0.2, 8.6±0.2, 12.5±0.2, 15.5±0.2, 17±0.2, 17.6±0.2, 19.3±0.2, 21.4±0.2, 21.4±0.2, 23±0.2, 23.3±0.2, 24.5±0.2, and 27.3±0.2.Attorney Docket No.: TGO-027WO 47. The process of claim 22 or 23, wherein Form B has an X-ray powder diffraction (XRPD) pattern comprising 2θ angles of 4.3±0.2, 8.6±0.2, 12.5±0.2, 15.5±0.2, 17±0.2, 17.6±0.2, 19.3±0.2, 21.4±0.2, 21.4±0.2, 23±0.2, 23.3±0.2, 24.5±0.2, and 27.3±0.

2.

48. The process of any one of claims 1 to 47, wherein hydrogenating a compound of Formula A1 comprises contacting the compound of Formula A1 with a first catalyst.

49. The process of claim 48, wherein hydrogenating the compound of Formula A1 comprises contacting the compound of Formula A1 with about 1 mol% to about 2 mol% of a first catalyst.

50. The process of claim 48 or 49, wherein the first catalyst is a palladium catalyst.

51. The process of claim 50, wherein the first catalyst is a palladium (0) catalyst.

52. The process of claim 50, wherein the first catalyst is palladium on carbon.

53. The process of any one of claims 1 to 52, wherein hydrogenating the compound of Formula A1 comprises the use of a flow system.

54. The process of claim 53, wherein hydrogenating a compound of Formula A1 comprises contacting the compound of Formula A1 with a second acid.

55. The process of any one of claims 1 to 52, wherein hydrogenating the compound of Formula A1 comprises the use of a batch system.

56. The process of any one of claims 1 to 55, wherein hydrogenating the compound of Formula A1 comprises contacting the compound of Formula A1 with hydrogen gas at a pressure of between about 2.0 megapascal (MPa) and 3.0 megapascal (MPa).

57. The process of any one of claims 1 to 56, wherein hydrogenating the compound of Formula A1 comprises elevating reaction temperature to about 55 °C to about 75 °C.

58. The process of any one of claims 1 to 57, wherein enzymatically amidating a compound of Formula A2 comprises contacting the compound of Formula A2 with a first enzyme.Attorney Docket No.: TGO-027WO 59. The process of claim 58, wherein enzymatically amidating a compound of Formula A2 comprises contacting the compound of Formula A2 with about 1% to about 3% by weight of the first enzyme.

60. The process of claim 58 or 59, wherein the first enzyme is an enzyme capable of catalyzing the enzymatic amidation of a compound of Formula A2 to a compound of Formula B.

61. The process of claim 58 or 59, wherein the first enzyme is pyridoxal phosphate.

62. The process of any one of claims 58 to 61, wherein enzymatically amidating a compound of Formula A2 comprises contacting the compound of Formula A2 with a second enzyme.

63. The process of claim 62, wherein enzymatically amidating a compound of Formula A2 comprises contacting the compound of Formula A2 with about 1% to about 3% by weight of the second enzyme.

64. The process of claim 62 or 63, wherein the second enzyme is an amine transaminase.

65. The process of claim 64, wherein the second enzyme is an engineered amine transaminase capable of catalyzing the enzymatic amidation of a compound of Formula A2 to a compound of Formula B.

66. The process of claim 64, wherein the second enzyme is ATA-22403.

67. The process of any one of claims 1 to 66, wherein cross-coupling a compound of Formula C with a compound of Formula D comprises converting the compound of Formula C to a compound of Formula C-1: Formula C-1,or a salt thereof, wherein: R2is a nitrogen protecting group; and R4is alkyl sulfonate, haloalkyl sulfonate, or aryl sulfonate.Attorney Docket No.: TGO-027WO 68. The process of claim 67, wherein converting the compound of Formula C to a compound of Formula C-1, or a salt thereof, comprises contacting the compound of Formula C with a dehydrating agent.

69. The process of claim 68, wherein the dehydrating agent is 1,1,1-trifluoro-N-phenyl-N- (trifluoromethanesulfonyl)methanesulfonamide (PhNTf2).

70. The process of any one of claims 1 to 69, wherein converting the compound of Formula C to a compound of Formula C-1, or a salt thereof, comprises contacting the compound of Formula C with a third base.

71. The process of claim 70, wherein the third base is a lithium base.

72. The process of claim 70, wherein the third base is lithium bis(trimethylsilyl)amide (LiHMDS).

73. The process of any one of claims 1 to 72, wherein converting the compound of Formula C to a compound of Formula C-1, or a salt thereof, comprises lowering reaction temperature to about -20º C to about -10 °C.

74. The process of any one of claims 1 to 73, wherein cross-coupling a compound of Formula C with a compound of Formula D comprises contacting a compound of Formula C-1, or a salt thereof, with the compound of Formula D, or a salt thereof, in the presence of a second catalyst.

75. The process of claim 74, wherein cross-coupling a compound of Formula C with a compound of Formula D comprises contacting a compound of Formula C-1, or a salt thereof, with the compound of Formula D, or a salt thereof, in the presence of less than about 5 mol% of the second catalyst.

76. The process of claim 74, wherein cross-coupling a compound of Formula C with a compound of Formula D comprises contacting a compound of Formula C-1, or a salt thereof, with the compound of Formula D, or a salt thereof, in the presence of about 3 mol% of the second catalyst.

77. The process of any one of claims 74 to 76, wherein the second catalyst is a palladium catalyst.Attorney Docket No.: TGO-027WO 78. The process of claim 77, wherein the second catalyst is [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II).

79. The process of any one of claims 1 to 78, wherein cross-coupling a compound of Formula C with a compound of Formula D comprises contacting a compound of Formula C-1, or a salt thereof, with the compound of Formula D, or a salt thereof, in the presence of a fourth base.

80. The process of claim 79, wherein the fourth base is Na2CO3.

81. The process of any one of claims 1 to 80, wherein removing nitrogen protecting group from a compound of Formula E comprises contacting the compound of Formula E with a first acid.

82. The process of claim 81, wherein the first acid is hydrochloric acid.

83. The process of any one of claims 1 to 82, wherein reducing a compound of Formula F comprises contacting the compound of Formula F with a reducing agent.

84. The process of claim 83, wherein the reducing agent is sodium borohydride (NaBH4).

85. The process of any one of claims 1 to 84, wherein enzymatically reducing a compound of Formula F comprises contacting the compound of Formula F with a third enzyme.

86. The process of claim 85, wherein the third enzyme is an imine reductase.

87. The process of claim 86, wherein the third enzyme is a naturally occurring (wild-type) imine reductase.

88. The process of claim 86, wherein the third enzyme is an engineered imine reductase capable of catalyzing the reducing of a compound of Formula F to a compound of Formula G.

89. The process of claim 86, wherein the third enzyme is IRED-23182.

90. The process of any one of claims 1 to 89, wherein enzymatically reducing a compound of Formula F comprises contacting the compound of Formula F with a fourth enzyme.

91. The process of claim 90, wherein the fourth enzyme is a glutamate dehydrogenase.Attorney Docket No.: TGO-027WO 92. The process of any one of claims 1 to 91, wherein enzymatically reducing a compound of Formula F comprises contacting the compound of Formula F with nicotinamide adenine dinucleotide phosphate (NADP).

93. The process of any one of claims 1 to 92, wherein enzymatically reducing a compound of Formula F comprises contacting the compound of Formula F comprises contacting the compound of Formula F with a sugar.

94. The process of claim 93, wherein the sugar is glucose.

95. The process of any one of claims 1 to 94, wherein enzymatically reducing a compound of Formula F comprises contacting the compound of Formula F comprises contacting the compound of Formula F with a buffer.

96. The process of claim 95, wherein the buffer comprises K2HPO4 and KH2PO4.

97. The process of any one of claims 1 to 96, wherein coupling a compound of Formula G with a compound of Formula H comprises contacting the compound of Formula G, or a salt thereof, with a compound of Formula H, or a salt thereof.

98. The process of any one of claims 1 to 97, wherein coupling a compound of Formula G with a compound of Formula H comprises contacting the compound of Formula G, or a salt thereof, with a compound of Formula H, or a salt thereof, in the presence of a coupling reagent.

99. The process of claim 98, wherein the coupling reagent is an anhydride coupling reagent; a triazole-based coupling reagent; a carbodiimide coupling reagent; an imidazolium coupling reagent; a phosphonium salt coupling reagent; or a pyridinium salt coupling reagent.

100. The process of claim 98, wherein the coupling reagent is 2-(1H-benzotriazole-1-yl)- 1,1,3,3-tetramethylaminium tetrafluoroborate (TBTU).

101. The process of any one of claims 1 to 100, wherein coupling a compound of Formula G with a compound of Formula H comprises contacting the compound of Formula G, or a salt thereof, with a compound of Formula H, or a salt thereof, in the presence of a fifth base.

102. The process of claim 101, wherein the fifth base is N-methylmorpholine (NMM).Attorney Docket No.: TGO-027WO 103. The process of any one of claims 1 to 102, wherein coupling a compound of Formula G with a compound of Formula H comprises contacting the compound of Formula G with a compound of Formula H, or a salt thereof, in the presence of a third acid.

104. The process of claim 103, wherein the third acid is formic acid.

105. The process of any one of claims 1 to 104, wherein coupling a compound of Formula G with a compound of Formula H results in a first salt of Formula I.

106. The process of claim 105, wherein the first salt of Formula I is: .

107. The process of any one of claims 1 to 106, wherein removing one or more nitrogen protecting groups from a first salt of a compound of Formula I comprises contacting the first salt of the compound of Formula I with a fourth acid.

108. The process of claim 107, wherein the fourth acid is phosphoric acid (H3PO4).

109. The process of any one of claims 1 to 108, wherein removing one or more nitrogen protecting groups from a first salt of a compound of Formula I results in a second salt of a compound of Formula I.

110. The process of claim 109, wherein the second salt of a compound of Formula I isAttorney Docket No.: TGO-027WO 111. The process of any one of claims 1 to 110, wherein free-basing a second salt of a compound of Formula I comprises contacting the second salt of the compound of Formula I with a sixth base.

112. The process of claim 111, wherein the sixth base is sodium carbonate.

113. The process of any one of claims 6 to 112, wherein pivalamide protecting a compound of Formula J, or a salt thereof, comprises contacting the compound of Formula J, or a salt thereof, with pivaloyl chloride (trimethylacetyl chloride).

114. The process of any one of claims 6 to 113, wherein pivalamide protecting a compound of Formula J, or a salt thereof, comprises contacting the compound of Formula J, or a salt thereof, with a seventh base.

115. The process of claim 114, wherein the seventh base is triethylamine (TEA).

116. The process of any one of claims 6 to 115, wherein pivalamide protecting a compound of Formula J, or a salt thereof, comprises lowering the reaction temperature to between about -10 °C and about 10 °C.

117. The process of any one of claims 6 to 116, wherein converting the compound of Formula K, or a salt thereof, to a compound of Formula L, or a salt thereof, comprises contacting the compound of Formula K, or a salt thereof, with an eighth base.

118. The process of claim 117, wherein the eighth base is a lithium base.

119. The process of claim 117, wherein the eighth base is n-butyllithium.

120. The process of any one of claims 6 to 119, wherein contacting the compound of Formula K with the eighth base comprises lowering reaction temperature to below 0° C.

121. The process of any one of claims 6 to 119, wherein contacting the compound of Formula K with the eighth base comprises lowering reaction temperature to between about - 10 ºC to about 0 °C.

122. The process of any one of claims 6 to 121, wherein converting the compound of Formula K, or a salt thereof, to a compound of Formula L, or a salt thereof, comprisesAttorney Docket No.: TGO-027WO contacting the compound of Formula K, or a salt thereof with N-Methoxy-N- methylacetamide.

123. The process of claim 122, wherein contacting the compound of Formula K, or a salt thereof with N-Methoxy-N-methylacetamide comprises lowering reaction temperature to between about -60 ºC to about -40 °C.

124. The process of any one of claims 6 to 123, wherein converting the compound of Formula K, or a salt thereof, to a compound of Formula L, or a salt thereof is performed in a continuous stirred tank reactor or a series of continuous stirred tank reactors.

125. The process of any one of claims 6 to 124, wherein reducing the carbonyl group and deprotecting the pivalamide of a compound of Formula L or a salt thereof, comprises contacting the compound of Formula L with hydrazine hydrate.

126. The process of any one of claims 6 to 125, wherein reducing the carbonyl group and deprotecting the pivalamide of a compound of Formula L or a salt thereof, comprises contacting the compound of Formula L with a ninth base.

127. The process of claim 126, wherein the ninth base is KOH.

128. The process of any one of claims 6 to 127, wherein reducing the carbonyl group and deprotecting the pivalamide of a compound of Formula L or a salt thereof, comprises contacting the compound of Formula L with a fifteenth solvent.

129. The process of claim 128, wherein the fifteenth solvent is a high-boiling point solvent.

130. The process of claim 128 or 129, wherein the fifteenth solvent is triethylene glycol.

131. The process of any one of claims 6 to 130, wherein reducing the carbonyl group and deprotecting the pivalamide of a compound of Formula L or a salt thereof, comprises elevating reaction temperature to between about 180 °C to about 220 °C.

132. The process of any one of claims 6 to 130, wherein reducing the carbonyl group and deprotecting the pivalamide of a compound of Formula L or a salt thereof, comprises elevating reaction temperature to between about 190 °C to about 210 °C.Attorney Docket No.: TGO-027WO 133. The process of any one of claims 6 to 132, wherein reducing the carbonyl group and deprotecting the pivalamide of a compound of Formula L or a salt thereof is performed in a plug flow reactor (PFR).

134. The process of any one of claims 6 to 133, wherein nitration of a compound of Formula M, or a salt thereof, comprises contacting the compound of Formula M with a mixture of sulfuric acid (H2SO4) and nitric acid (HNO3).

135. The process of any one of claims 6 to 134, wherein nitration of a compound of Formula M, or a salt thereof, is performed in a plug flow reactor (PFR).

136. The process of any one of claims 6 to 135, wherein nitrogen protection of a compound of Formula N, or a salt thereof, comprises contacting the compound of Formula N with a second nitrogen protecting group reagent.

137. The process of any one of claims 6 to 136, wherein nitrogen protection of a compound of Formula N, or a salt thereof, comprises contacting the compound of Formula N with an eighth base.

138. The process of claim 137, wherein the eighth base is dimethylamino pyridine (DMAP).

139. The process of any one of claims 6 to 138, wherein nitrogen protection of a compound of Formula N, or a salt thereof, comprises lowering the reaction temperature to below about 20 °C.

140. The process of any one of claims 6 to 138, wherein nitrogen protection of a compound of Formula N, or a salt thereof, comprises lowering the reaction temperature to between about 8 °C and about 18 °C.

141. The process of any one of claims 6 to 140, wherein nitro reduction of a compound of Formula P, or a salt thereof, comprises contacting the compound of Formula P, or a salt thereof, with a third catalyst.

142. The process of any one of claims 6 to 140, wherein hydrogenating the compound of Formula P, or a salt thereof, comprises contacting the compound of Formula P with less than about 40 % w / w of a third catalyst.Attorney Docket No.: TGO-027WO 143. The process of any one of claims 6 to 140, wherein hydrogenating the compound of Formula P, or a salt thereof, comprises contacting the compound of Formula P, or a salt thereof, with about 20 % w / w to about 35 % w / w of a third catalyst.

144. The process of any one of claims 6 to 143, wherein the third catalyst is nickel on carbon.

145. The process of any one of claims 6 to 144, wherein hydrogenating the compound of Formula P, or a salt thereof, comprises contacting the compound of Formula P, or a salt thereof, with hydrogen.

146. The process of any one of claims 6 to 144, wherein hydrogenating the compound of Formula P, or a salt thereof, comprises contacting the compound of Formula P, or a salt thereof, with hydrogen at a pressure of at least about 2 MPa (e.g., between about 2 MPa and about 3 MPa).

147. The process of any one of claims 6 to 146, wherein hydrogenating the compound of Formula P, or a salt thereof, comprises elevating reaction temperature to about 40 °C to about 60 °C.

148. The process of any one of claims 6 to 147, wherein oxalylamide installation on a compound of Formula P, or a salt thereof, comprises contacting the compound of Formula P with wherein R12is C1-C6alkyl.

149. The process of any one of claims 6 to 148, wherein oxalylamide installation on a compound of Formula P, or a salt thereof, comprises contacting the compound of Formula P with a tenth base.

150. The process of claim 149, wherein the tenth base is triethylamine (TEA).

151. The process of any one of claims 6 to 150, wherein saponification of a compound of Formula R, or a salt thereof, comprises contacting the compound of Formula R with an eleventh base.

152. The process of claim 151, wherein the eleventh base is LiOH.Attorney Docket No.: TGO-027WO 153. The process of any one of claims 1 to 152, wherein R1is an optionally substituted oxazolidinone.

154. The process of any one of claims 1 to 152, wherein R1is , wherein R10isalkyl, benzyl (Bn), or phenyl (Ph).

155. The process of any one of claims 1 to 154, wherein R1is .

156. The process of any one of claims 1 to 155, wherein R2is a carbamate group. The process of any one of claims 1 to 155, wherein R2is .

158. The process of any one of claims 1 to 157, wherein R3is a boronic ester. 3159. The process of claim 158, wherein R is , wherein each of R3aand R3bis, independently, H or C1-6alkyl, wherein R3aand R3bare optionally joined together with their intervening atoms to form a 5-10 membered ring that is optionally substituted with 0, 1, 2, 3, 4, 5, or 6 instances of R3c, wherein each R3cis, independently, C1-6alkyl.

160. The process of claim 159, wherein R3is .

161. The process of any one of claims 1 to 160, wherein R6is a carbamate.

162. The process of claim 161, wherein R6is .

163. The process of any one of claims 1 to 162, wherein R7is a carbamate.Attorney Docket No.: TGO-027WO 164. The process of any one of claims 1 to 163, wherein R7is .

165. The process of any one of claims 1 to 164, wherein R8is a nitrogen protecting group and R9is a nitrogen protecting group.

166. The process of any one of claims 1 to 164, wherein R8is a nitrogen protecting group and R9is H.

167. The process of any one of claims 1 to 164, wherein R8is and R9is.

168. The process of any one of claims 1 to 164, wherein R8is and R9is H.

169. The process of any one of claims 6 to 168, wherein R12is –Me, –Et, –nPr, –iPr, –nBu, or –tBu.

170. The process of any one of claims 6 to 168, wherein R12is –Et.

171. A crystalline Form A of Compound A: .wherein Form A has an X-ray powder diffraction (XRPD) pattern comprising one or more peaks at 2θ angles selected from 11.6±0.2, 11.7±0.2, 14.5±0.2, 16.6±0.2, 17.2±0.2, 17.5±0.2, 17.6±0.2, 19±0.2, and 24.9±0.

2.

172. The crystalline Form A of Compound A of claim 171, wherein Form A has an X-ray powder diffraction (XRPD) pattern comprising 2θ angles of 11.6±0.2, 11.7±0.2, 14.5±0.2, 16.6±0.2, 17.2±0.2, 17.5±0.2, 17.6±0.2, 19±0.2, and 24.9±0.2.Attorney Docket No.: TGO-027WO 173. A crystalline Form B of Compound B: .wherein Form B has an X-ray powder diffraction (XRPD) pattern comprising one or more peaks at 2θ angles selected from 4.3±0.2, 8.6±0.2, 12.5±0.2, 15.5±0.2, 17±0.2, 17.6±0.2, 19.3±0.2, 21.4±0.2, 21.4±0.2, 23±0.2, 23.3±0.2, 24.5±0.2, and 27.3±0.

2.

174. The crystalline Form B of Compound B of claim 173, wherein Form B has an X-ray powder diffraction (XRPD) pattern comprising 2θ angles of 4.3±0.2, 8.6±0.2, 12.5±0.2, 15.5±0.2, 17±0.2, 17.6±0.2, 19.3±0.2, 21.4±0.2, 21.4±0.2, 23±0.2, 23.3±0.2, 24.5±0.2, and 27.3±0.2.

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