P0043-WO-PCT/P0043-WO 37JD-350579-WO PROCESSES FOR PREPARING AZOLOPYRIMIDINE COMPOUNDS CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit to United States Provisional Application No. 63/381,986, filed November 2, 2022, which is hereby incorporated by reference in its entirety. FIELD OF THE DISCLOSURE [0002] The present disclosure relates to processes for preparing azolopyrimidine compounds (including etrumadenant), process intermediates useful for the preparation of azolopyrimidine compounds, and pharmaceutical compositions comprising the same. BACKGROUND [0003] Etrumadenant (also known as AB928) is a selective dual antagonist of adenosine A2a and A2b receptors under study in clinical trials for several indications. Its structure is characterized, in part, by a central triazole appended with pyrimidine and pyridine rings. A synthetic route to AB928 featuring a convergent Cu-catalyzed [3+2] cycloaddition of an alkynyl pyrimidine and azidomethyl pyridine has been described (see, for example, Sharif, et al., Development of a scalable synthesis of AB928, a dual A2a/A2b receptor antagonist. Org. Proc. Res. Dev.2020, 24, 1254-1261, and WO2020023846A1). [0004] Despite these advances, there is a continued need to improve synthetic processes for preparing etrumadenant and structurally related compounds, for example, to improve yields, purity, and scaling. The present disclosure addresses these needs and provides related advantages as well. SUMMARY OF THE DISCLOSURE [0005] In a first aspect, the instant disclosure is directed to compositions comprising etrumadenant, or a pharmaceutically acceptable salt thereof. etrumadenant. P0043-WO-PCT/P0043-WO 37JD-350579-WO [0006] The compositions comprising etrumadenant, or a pharmaceutically acceptable salt thereof, contain low levels of process impurities. In certain embodiments, the compositions are substantially free from one or more compounds selected from Compound (d), Compound (f), and Compound (g). [0007] In one embodiment, the composition comprises etrumadenant, or a pharmaceutically acceptable salt thereof, and the composition is substantially free of Compound (d) and Compound (f). In further embodiments, the composition comprises etrumadenant, or a pharmaceutically acceptable salt thereof, and is substantially free of Compound (g). In yet a further embodiment, the composition comprises etrumadenant, or a pharmaceutically acceptable salt thereof, and is substantially free of Compound (d), Compound (f), and Compound (g). [0008] The compositions described herein may be pharmaceutical compositions. The pharmaceutical compositions include etrumadenant, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients. The pharmaceutical composition may, in some embodiments, be substantially free of one or more compounds selected from Compound (d), Compound (f), and Compound (g). In one embodiment, the pharmaceutical composition is substantially free of Compound (d). In another embodiment, the pharmaceutical composition is P0043-WO-PCT/P0043-WO 37JD-350579-WO substantially free of Compound (f). In another embodiment, the pharmaceutical composition is substantially free of Compound (g). In some embodiments, the pharmaceutical composition is substantially free of Compound (d) and Compound (f); and in some embodiments, the pharmaceutical composition is substantially free of Compound (d), Compound (f), and Compound (g). In some embodiments, the pharmaceutical composition comprises etrumadenant, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients, wherein the pharmaceutical composition is substantially free of one or more compounds selected from Compound (d) and Compound (f). [0009] The pharmaceutical compositions may be in a form suitable for oral use, for example, as tablets, capsules, troches, lozenges, aqueous or oily suspensions, dispersible powders or granules, emulsions, hard or soft capsules, or syrups, solutions, microbeads, or elixirs. Tablets, capsules and the like contain etrumadenant, or a pharmaceutically acceptable salt thereof, in admixture with non- toxic pharmaceutically acceptable excipients which are suitable for the manufacture of tablets. These excipients may be, for example, diluents, such as calcium carbonate, sodium carbonate, lactose, calcium phosphate, microcrystalline cellulose, mannitol, or sodium phosphate; granulating and disintegrating agents, for example, corn starch, croscarmellose sodium, or alginic acid; binding agents, for example, starch, gelatin, or acacia; lubricating agents, for example, magnesium stearate, sodium stearyl fumarate, stearic acid, or talc; and glidants, for example, colloidal silica. [0010] In various embodiments, the pharmaceutical composition includes one or more polymers selected from hydroxypropylmethylcellulose acetate succinate (HPMCAS), copovidone (PVP-VA), cellulose acetate phthalate (CAP), hydroxypropyl methylcellulose E3 (HPMC E3), hydroxypropyl methylcellulose phthalate (HPMCP), polyvinylpyrrolidone (PVP), and polyvinyl caprolactam– polyvinyl acetate–polyethylene glycol graft copolymer. [0011] In various embodiments, the pharmaceutical composition includes one or more fillers, one or more disintegrants, optionally one or more glidants, and optionally one or more lubricants. [0012] The instant disclosure further relates to compounds of Formula (IIa-i) and Formula (IIa- ii) and processes for preparing these compounds. P0043-WO-PCT/P0043-WO 37JD-350579-WO X is ii) [0013] Compounds of Formula (IIa-i) and Formula (IIa-ii) are useful in the manufacture of etrumadenant. The compounds of Formula (IIa-i) (and compounds of Formula (IIa-ii)) may be prepared by a process comprising: (a) contacting a compound of Formula (III) with a halogenation reagent to form a compound of Formula (IV): wherein R ¹ is a C1-C6 alkyl, and X is a halo; (b) contacting the compound of Formula (IV) with a methyl magnesium Grignard reagent to form a compound of Formula (II); and (c) contacting the compound of Formula (II) with an acid to form the compound of Formula (IIa-i). [0014] Nonlimiting examples of useful methyl magnesium Grignard reagents include methyl magnesium fluoride, methyl magnesium chloride, methyl magnesium bromide, and methyl magnesium iodide. [0015] Nonlimiting examples of halogenation reagents include pyridinium poly(hydrogen fluoride), thionyl fluoride, carbon tetrachloride, methanesulfonyl chloride, sulfuryl chloride, thionyl chloride, cyanuric chloride, N-chlorosuccinateimide, phosphorus oxychloride (V), phosphorus pentachloride, and phosphorus trichloride, hydrobromic acid, carbon tetrabromide, phosphorus tribromide, potassium bromide, hydroiodic acid, thionyl bromide, carbon tetraiodide, phosphorus P0043-WO-PCT/P0043-WO 37JD-350579-WO triiodide, sodium iodide, potassium iodide, and thionyl iodide. In some embodiments, the halogenation reagent is thionyl chloride (SOCl2). [0016] In one embodiment, the process further comprises contacting a compound of Formula (IIa-i) with a base to form the compound of Formula (II), wherein X is a halo. [0017] In some embodiments, the halo is fluoro, chloro, bromo, or iodo. In one embodiment, the halo is chloro. [0018] The process may further comprise contacting a compound of Formula (II) with an azide salt to form Compound (16): [0019] Nonlimiting examples of azide salts include sodium azide, potassium azide, lithium azide, and cesium azide. In certain embodiments, the azide salt is sodium azide. [0020] As described herein, the compound of Formula (IIa-ii) can exist in a crystalline form. Therefore, the instant disclosure relates to a crystalline form of the compound of Formula (IIa-ii). In one embodiment, the crystalline form of the compound of Formula (IIa-ii) has one or more X-ray powder diffraction signals at 2θ values obtained with CuKα1-radiation of 18.7±0.2, 22.6±0.2, 23.3±0.2, and 28.1±0.2. In another embodiment, the crystalline form of the compound of Formula (IIa-ii) is characterized by two, three, or more X-ray powder diffraction signals at 2θ values obtained with CuKα1-radiation of 18.7±0.2, 22.6±0.2, 23.3±0.2, and 28.1±0.2. The crystalline form may be further characterized by one or more signals at 2θ values obtained with CuKα1-radiation at 9.4±0.2, 14.5±0.2, 15.8±0.2, 18.9±0.2, 21.9±0.2, and 22.1±0.2. P0043-WO-PCT/P0043-WO 37JD-350579-WO [0021] Finally, various processes for preparing etrumadenant are described throughout the instant disclosure. In one embodiment, the instant disclosure relates to a process for preparing etrumadenant comprising: (a) contacting a compound of Formula (II) with an azide salt to form Compound (16): (b) combining Compound (16) and Compound (8) with a copper catalyst to form etrumadenant: [0022] Nonlimiting examples of azide salts include sodium azide, potassium azide, lithium azide, and cesium azide. In some embodiments, the azide salt is sodium azide. [0023] In one embodiment, X is chloro. [0024] Nonlimiting examples of copper catalysts include copper (II) sulfate (CuSO4), copper (I) iodide (CuI), copper (I) bromide (CuBr), tetrakisacetonitrile copper(I) trifluoromethanesulfonate ((CH3CN)4CuOTf), copper (II) acetate (Cu(CH3COO)2), copper(II) trifluoromethanesulfonate (Cu(OTf)2), copper(II) carbonate basic (CuCO3*Cu(OH)2), copper(I) trifluoromethanesulfonate toluene (CuOTf *toluene), tetrakis(acetonitrile)copper(I) hexafluorophosphate ([Cu(CH₃CN)₄]PF₆), tetrakis(acetonitrile)copper(I) tetrafluoroborate ([Cu(CH₃CN)₄]PF₆), and tetrakis(pyridine)copper(II) triflate ([Cu(Otf)2(py)4]). In one embodiment, the copper catalyst is tetrakisacetonitrile copper(I) triflate ((CH ₃ CN) ₄ CuOTf). [0025] In further embodiments, a compound of Formula (II), wherein X is chloro (Compound 13)), may be prepared by contacting the compound of Formula (IIa-ii) with a base to form Compound (13): P0043-WO-PCT/P0043-WO 37JD-350579-WO [0026] Nonlimiting examples of bases include inorganic and organic bases, for example, bases selected from metal hydroxides, carbonates, phosphates, tertiary amines, and aryl amines, such as potassium bicarbonate, sodium bicarbonate, sodium carbonate, potassium carbonate, cesium carbonate, potassium fluoride, potassium phosphate dibasic, potassium phosphate tribasic, sodium hydroxide, potassium hydroxide, dicyclohexylamine, N-methylmorpholine, and triethylamine. In one embodiment, the base is sodium hydroxide, ammonium hydroxide, or a combination thereof. In another embodiment, the base is sodium hydroxide. [0027] The process may further comprise obtaining Compound (8) by contacting a compound of Formula (V) with a desilylation agent in the presence of a buffering agent: NH ₂ NH ₂ CN wherein PG is an alkyne protecting group. [0028] Nonlimiting examples of desilyation agents include ammonia, aqueous sodium hydroxide solution, potassium carbonate, dilute hydrochloric acid, dilute sulfuric acid, dilute trifluoroacetic acid or acetic acid, tetramethylammonium hydroxide, tetrabutylammonium hydroxide, tetrahexylammonium hydroxide, tetraoctylammonium hydroxide, phenyltrimethylammonium hydroxide, (3-trifluoro Methylphenyl) trimethylammonium hydroxide and (2-hydroxyethyl) trimethylammonium hydroxide (so-called “choline”). In one embodiment, the desilylation agent is tetrabutylammonium hydroxide (TBAH). [0029] Nonlimiting examples of buffering agents include K2HPO4, KH2PO4, H3PO4, and a combination thereof. In some embodiments, the buffering agent is selected from K ₂ HPO ₄ , H ₃ PO ₄ , and a combination thereof. In one embodiment, the buffering agent is H ₃ PO ₄ . P0043-WO-PCT/P0043-WO 37JD-350579-WO BRIEF DESCRIPTION OF THE DRAWINGS [0030] FIG. 1 shows the solubility of the compound of Formula (IIa-ii) in various solvents (x- axis) plotted against the supernatant purity on the y-axis. The solubility of critical impurities in each solvent is represented by the size of each circle, (i.e., larger circles indicate higher solubility of impurities); [0031] FIG. 2 shows results of a small-scale manufacture of the compound of Formula (IIa-ii) providing 90% yield and a purity of 98.8% determined by high-performance liquid chromatography (HPLC); [0032] FIG. 3 shows the solubility of the compound of Formula (IIa-ii) in various solvents; [0033] FIG.4 shows results of a large-scale manufacture of etrumadenant providing 90% yield and a purity of 99.5% determined by high-performance liquid chromatography (HPLC); [0034] FIG. 5 shows the X-ray powder diffraction pattern at 2θ values obtained with CuKα1- radiation for a crystalline form of Formula (IIa-ii); [0035] FIG. 6 shows Dynamic Vapor Sorption (DVS) characteristics of a crystalline form of the compound of Formula (IIa-ii); [0036] FIG.7 shows 98.3% conversion with 96.0% purity of Compound (16) measured by high- performance liquid chromatography (HPLC); and [0037] FIG. 8 shows a representative HPLC chromatogram of isolated etrumadenant obtained according to the methods described throughout the instant disclosure. DETAILED DESCRIPTION OF THE DISCLOSURE [0038] Before the present disclosure is further described, it is to be understood that the disclosure is not limited to the embodiments set forth herein, and it should also be understood that the terminology used herein is for purposes of describing various embodiments and not limiting. P0043-WO-PCT/P0043-WO 37JD-350579-WO I. Definitions [0039] The terms “comprising,” “including,” and “having” are intended to be inclusive and mean that there may be additional elements other than the listed elements. [0040] The terms “a,” “an,” and “the” are understood to encompass the plural as well as the singular. Thus, the term “a mixture thereof” (or “combination thereof) also relates to “mixtures thereof” (or “combinations thereof”). Likewise, the term “a salt thereof” also relates to “salts thereof.” [0041] The term “about” as used herein has its original meaning of approximately and is used to provide literal support for the exact number that it precedes, as well as a number that is near to or approximately the number that the term precedes. In general, the term “about” refers to the usual error range for the respective value readily known to the skilled person in this technical field. If the degree of approximation is not otherwise clear from the context, “about” means either within plus or minus 10% of the provided value, or rounded to the nearest significant figure, in all cases inclusive of the provided value. For example, about 50% includes a range of from 45% to 55%, while about 2.0 molar equivalents includes a range of from 1.8 to 2.2 molar equivalents. Accordingly, when referring to a range, “about” refers to each of the stated values +/- 10% of the stated value of each end of the range. For instance, a ratio of from about 1 to about 3 (weight/weight) includes a range of from 0.9 to 3.3. Where ranges are provided, they are inclusive of the boundary values. [0042] “Alkyl” is a linear or branched saturated monovalent hydrocarbon. For example, an alkyl group can have 1 to 6 carbon atoms (i.e., -C ₁ -C ₆ alkyl) or 1 to 4 carbon atoms (i.e., -C ₁ -C ₄ alkyl) or 1 to 3 carbon atoms (i.e., -C1-C3 alkyl). The term “alkyl” encompasses straight and branched-chain hydrocarbon groups. Examples of alkyl groups include, but are not limited to, methyl, ethyl, n- propyl, iso-propyl, n-butyl, iso-butyl, tert-butyl, sec-butyl, n-pentyl, 2,2-dimethylpropyl, 3- methylbutyl, sec-pentyl, 2-methylbutyl, iso-hexyl, sec-hexyl, tert-hexyl, and the like. In some embodiments, the alkyl group is a -C1-C3 alkyl (e.g., methyl, ethyl, n-propyl, or iso-propyl). In one embodiment, the alkyl group is methyl. P0043-WO-PCT/P0043-WO 37JD-350579-WO [0043] “Halo” or “halogen” as used herein refers to fluoro (-F), chloro (-Cl), bromo (-Br) and iodo (-I). In some embodiments, “halo” is chloro (-Cl) and bromo (-Br). In one embodiment, halo is chloro. [0044] “Purity” refers to chemical purity independent of stereochemistry preference unless otherwise indicated. [0045] “Catalyst” refers to a chemical reactant that increases the rate of a reaction without itself being consumed. [0046] As used herein, the term “counter anion” refers to a negatively charged species that is present to balance a positively charged species. Exemplary counter anions include, but are not limited to fluoride, chloride, bromide, iodide, methanesulfonate, benzenesulfonate, DL- camphorsulfonate, ethanesulfonate, naphthalene sulfonate, p-toluenesulfonate, hydrochlorate, phosphate, sulfate, trifluormethanesulfonate, acetate, aspartate, benzoate, bicarbonate, bitartrate, camsylate, carbonate, citrate, deconate, edetate, esylate, fumarate, gluceptate, gluconate, glutamate, glycolate, hexanoate, hydrozxynaphthoate, isethionate, lactate, malate, maleate, mandelate, mesylate, mucate, napsylate, nitrate, octanoate, oleate, pamoate, pantothenate, phosphate, polygalacturonate, propionate, salicylate, stearate, succinate, tartrate, teoclate, tosylate, and the like. [0047] “Protecting group” refers to a moiety of a compound that masks or alters the properties of a functional moiety. The protecting group can be removed so as to restore the functional moiety to its original state. Chemical protecting groups and strategies for protection/deprotection are well known in the art. See also Protective Groups in Organic Chemistry, Peter G. M. Wuts and Theodora W. Greene, 4th Ed., 2006. Protecting groups are often utilized to mask the reactivity of certain functional moieties, to assist in the efficiency of desired chemical reactions, e.g., making and breaking chemical bonds in an ordered and planned fashion. For example, an “alkyne protecting group” refers to a protecting group useful for masking the acetylenic hydrogen, e.g., to render the acetylenic hydrogen unreactive during intermediate steps of a synthetic process. Exemplary alkyne protecting groups include silane protecting groups (e.g., trimethylsilyl (TMS), triethylsilyl (TES), triisopropylsilyl (TIPS), tert-butylmethylsilyl (TBS or TBDMS), and tert-butyldiphenylsilyl (TBDPS)). In some embodiments, the protecting group is triisopropylsilyl (TIPS). P0043-WO-PCT/P0043-WO 37JD-350579-WO [0048] A “desilylation agent” is a chemical reactant that is capable of effecting removal of a silyl protecting group. For example, tetrabutylammonium hydroxide (TBAH) is capable of removing a triisopropylsilyl protecting group. [0049] In some embodiments, as used herein, the phrase “substantially free” means that the designated compound, material, or composition contains 3% (w/w) or less of chemical impurities. According to some embodiments, the designated compound, material, or composition contains 3% (w/w) or less, 2% (w/w) or less, 1% (w/w) or less, 0.5% (w/w) or less, or 0.2% (w/w) or less of chemical impurities. In other embodiments, the designated compound, material, or composition contains from 0.001% (w/w) to 3% (w/w), 0.001% (w/w) to 2% (w/w), 0.001% (w/w) to 1% (w/w), 0.001% (w/w) to 0.5% (w/w), or 0.001% (w/w) to 0.2% (w/w) of chemical impurities. In other embodiments, as used herein, the phrase “substantially free” means that the designated compound, material, or composition contains 3% (a/a) or less of chemical impurities as determined by HPLC. According to some embodiments, the designated compound, material, or composition contains 3% (a/a) or less, 2% (a/a) or less, 1% (a/a) or less, 0.5% (a/a) or less, or 0.2% (a/a) or less, or 0.1% (a/a) or less, or 0.05% (a/a) or less of chemical impurities as determined by HPLC. In further embodiments, the designated compound, material, or composition contains impurities below the limit of detection when analyzed via HPLC. In one or more embodiments, the designated compound, material, or composition contains impurities below the limit of quantitation when analyzed via HPLC. In some embodiments, the limit of quantitation when analyzed via HPLC is 0.05% (a/a). It is to be understood that the term “substantially free” does not exclude “completely” e.g., a composition which is substantially free of a designated compound, material, or composition may be completely free from the designated compound, material, or composition. [0050] As used herein, the terms “weight percent”, “% (w/w)”, and “%-w/w” are used interchangeably and refer to the ratio of a designated compound, material, or composition, divided by the total mass of the total composition, times 100. [0051] As used herein, the terms “area percent”, “%-a/a”, and “% (a/a)” are used interchangeably and refer to the area percent under the peak for a designated compound generated using chromatographic or spectroscopic methods generated during experimentation. Area percent is a measure of the ratio of the area under the peak for a designated compound, divided by the total area under all detectible and/or quantifiable observed peaks, times 100. P0043-WO-PCT/P0043-WO 37JD-350579-WO [0052] As used herein, the term “salt” includes partially or fully ionized salt forms. In some embodiments, the salt is fully ionized. [0053] The term “pharmaceutically acceptable salt” is meant to include salts of the active compounds which are prepared with relatively nontoxic acids or bases, depending on the particular substituents found on the compounds described herein. When compounds of the present disclosure contain relatively acidic functionalities, base addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired base, either neat or in a suitable inert solvent. Examples of salts derived from pharmaceutically acceptable inorganic bases include aluminum, ammonium, calcium, copper, ferric, ferrous, lithium, magnesium, manganic, manganous, potassium, sodium, zinc and the like. Salts derived from pharmaceutically-acceptable organic bases include salts of primary, secondary and tertiary amines, including substituted amines, cyclic amines, naturally-occurring amines and the like, such as arginine, betaine, caffeine, choline, N,N’-dibenzylethylenediamine, diethylamine, 2-diethylaminoethanol, 2-dimethylaminoethanol, ethanolamine, ethylenediamine, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, histidine, hydrabamine, isopropylamine, lysine, methylglucamine, morpholine, piperazine, piperidine, polyamine resins, procaine, purines, theobromine, triethylamine, trimethylamine, tripropylamine, tromethamine and the like. When compounds of the present disclosure contain relatively basic functionalities, acid addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired acid, either neat or in a suitable inert solvent. Examples of pharmaceutically acceptable acid addition salts include those derived from inorganic acids like hydrochloric, hydrobromic, nitric, carbonic, monohydrogencarbonic, phosphoric, monohydrogenphosphoric, dihydrogenphosphoric, sulfuric, monohydrogensulfuric, hydriodic, or phosphorous acids and the like, as well as the salts derived from relatively nontoxic organic acids like acetic, propionic, isobutyric, malonic, benzoic, succinic, suberic, fumaric, mandelic, phthalic, benzenesulfonic, p-tolylsulfonic, citric, tartaric, methanesulfonic, maleic, oxalic, trans-cinnamic, and the like. Also included are salts of amino acids such as arginate and the like, and salts of organic acids like glucuronic or galactunoric acids and the like (see, for example, Berge, S.M., et al., “Pharmaceutical Salts,” Journal of Pharmaceutical Science, 1977, 66, 1-19). Certain specific compounds of the present disclosure contain both basic and acidic functionalities that allow the compounds to be converted into either base or acid addition salts. P0043-WO-PCT/P0043-WO 37JD-350579-WO [0054] As used herein, the phrase “therapeutically effective amount” with reference to etrumadenant means a dose regimen (i.e., amount and interval) of the compound, or pharmaceutically acceptable salt thereof, that provides the specific pharmacological effect for which the compound is administered to a subject in need of such treatment. For prophylactic use, a therapeutically effective amount may be effective to eliminate or reduce the risk, lessen the severity, or delay the onset of the disease, including biochemical, histological and/or behavioral signs or symptoms of the disease. For treatment, a therapeutically effective amount may be effective to reduce, ameliorate, or eliminate one or more signs or symptoms associated with a disease, delay disease progression, prolong survival, decrease the dose of other medication(s) required to treat the disease, or a combination thereof. With respect to cancer specifically, a therapeutically effective amount may, for example, result in the killing of cancer cells, reduce cancer cell counts, reduce tumor burden, eliminate tumors or metastasis, or reduce metastatic spread. A therapeutically effective amount may vary based on, for example, one or more of the following: the age and weight of the subject, the subject’s overall health, the stage of the subject’s disease, the route of administration, and prior or concomitant treatments. [0055] The term “disintegrant” refers to a substance which, upon addition to a solid preparation, facilitates its break-up or disintegration after administration and permits the release of an active ingredient as efficiently as possible to allow for its rapid dissolution. Nonlimiting examples of disintegrants include maize starch, sodium starch glycolate, croscarmellose sodium, crospovidone, microcrystalline cellulose, modified corn starch, sodium carboxymethyl starch, povidone, pregelatinized starch, and alginic acid. [0056] The term “filler” (also known as a diluent) refers to chemical compounds that are used to dilute the compound of interest prior to delivery. Diluents can also serve to stabilize compounds. Non-limiting examples of diluents include starch, saccharides, disaccharides, sucrose, lactose, polysaccharides, cellulose, cellulose ethers, hydroxypropyl cellulose, sugar alcohols, xylitol, sorbitol, maltitol, microcrystalline cellulose, calcium or sodium carbonate, lactose, lactose monohydrate, dicalcium phosphate, cellulose, compressible sugars, dibasic calcium phosphate dehydrate, mannitol, microcrystalline cellulose, and tribasic calcium phosphate. [0057] The term “glidant” as used herein is intended to mean an agent used in tablet and capsule formulations to improve flow-properties during tablet compression and to produce an anti-caking P0043-WO-PCT/P0043-WO 37JD-350579-WO effect. Nonlimiting examples of glidants include colloidal silicon dioxide, talc, fumed silica, starch, starch derivatives, and bentonite. [0058] The term “lubricant” refers to an excipient which is added to a powder blend to prevent the compacted powder mass from sticking to the equipment during the tableting or encapsulation process. It aids the ejection of the tablet form and can improve powder flow. Nonlimiting examples of lubricants include magnesium stearate, stearic acid, silica, fats, or talc; and solubilizers such as fatty acids including lauric acid, oleic acid, and C ₈ /C ₁₀ fatty acid. [0059] As used herein, the term “halogenation reagent” means a reagent that converts an alcohol group into a halide group. The halogenation reagent may be a bromination reagent, an iodination reagent, or a chlorination reagent. The “bromination reagent” is a reagent that converts an alcohol group into a bromide group. The “iodination reagent” is a reagent that converts an alcohol group into an iodide group. The “chlorination reagent” is a reagent that converts an alcohol group into a chloride group. [0060] As used herein, the term “magnesium Grignard reagent” refers to a chemical compound with the general formula R-Mg-X, where X is a halogen, and R is an alkyl group as defined herein. Magnesium Grignard reagents are useful to effect chemical transformations, such as, for example, conversion of esters to tertiary alcohols. As used herein, the term “methyl magnesium Grignard reagent” refers to a Grignard reagent as defined herein, wherein the R group is methyl. Exemplary methyl magnesium Grignard reagents include, but are not limited to, methyl magnesium fluoride, methyl magnesium chloride, methyl magnesium bromide, and methyl magnesium iodide. [0061] As used herein, the term “buffering agent” refers to an agent that results in a solution that resists pH change upon the addition of acidic or basic components. A solution comprising a buffering agent contains either a weak acid and its conjugate base, or a weak base and its conjugate acid. Exemplary buffering agents comprise phosphate, diphosphate, citrate, acetate, lactate, or combinations thereof. In some embodiments, the buffering agent is dipotassium phosphate (K2HPO4), potassium dihydrogen phosphate (KH2PO4), phosphoric acid (H3PO4), or combinations thereof. It is to be understood that if a buffering agent is added in its acidic form (e.g., H ₃ PO ₄ ), its conjugate base (e.g., H2PO4 ^— ) is formed in solution due to the presence of a base that is present, or is subsequently added, in the solution. Similarly, if a buffering agent is added in its basic form (e.g., P0043-WO-PCT/P0043-WO 37JD-350579-WO K ₂ HPO ₄ ), its conjugate acid (H ₂ PO ₄ ^— ) is formed in solution due to the presence of an acid that is present, or is subsequently added, in the solution. [0062] As used herein, an “individual” or a “subject” includes animals, such as human (e.g., human individuals) and non-human animals. In some embodiments, an “individual” or “subject” is a patient under the care of a physician. Thus, the subject can be a human patient or an individual who has, is at risk of having, or is suspected of having a disease of interest (e.g., cancer) and/or one or more symptoms of the disease. The subject can also be an individual who is diagnosed with a risk of the condition of interest at the time of diagnosis or later. The term “non-human animals” includes all vertebrates, e.g., mammals, non-human primates, and other mammals. II. Etrumadenant and Compositions Comprising Etrumadenant [0063] Etrumadenant (also known as AB928) is a selective, dual antagonist of the adenosine 2a receptor (A2aR) and the adenosine 2b receptor (A2bR). Its chemical name is 3-[2-amino-6-(1-{[6-(2- hydroxypropan-2-yl)pyridin-2-yl]methyl}-1H-1,2,3-triazol-4-y l)pyrimidin-4-yl]-2- methylbenzonitrile, and its structural formula is shown below. [0064] Methods for making etrumadenant are known in the art. For example, see WO 2018/136700, WO 2020/018680, and WO 2020/247789, the disclosures of which are incorporated herein by reference in their entirety. [0065] The instant disclosure is drawn to compositions comprising etrumadenant, or a pharmaceutically acceptable salt thereof, wherein the compositions is substantially free from one or more compounds selected from Compound (d), Compound (f), and Compound (g). P0043-WO-PCT/P0043-WO 37JD-350579-WO [0066] Compound (d), Compound (f), and Compound (g) represent various process impurities that can arise during the manufacture of etrumadenant, and thus it is advantageous to limit or exclude them. For example, these impurities may arise when carrying out the processes for manufacturing of etrumadenant, or a pharmaceutically acceptable salt thereof, as set forth throughout the instant disclosure. [0067] The unique processes described herein, however, are particularly useful for minimizing or eliminating impurities during the manufacture of etrumadenant, including Compound (d), Compound (f), and Compound (g). The processes described herein provide for substantially pure etrumadenant, or a pharmaceutically acceptable salt thereof, wherein the etrumadenant, or pharmaceutically acceptable salt thereof, is substantially free of impurities, including Compound (d), Compound (f), and/or Compound (g). Accordingly, compositions, such as pharmaceutical compositions, comprising etrumadenant, or a pharmaceutically acceptable salt thereof, are likewise substantially free of impurities, including Compound (d), Compound (f), and/or Compound (g). P0043-WO-PCT/P0043-WO 37JD-350579-WO III. Pharmaceutical Compositions [0068] Etrumadenant may be provided in a composition suitable for administration to a subject. In general, such compositions are “pharmaceutical compositions” comprising etrumadenant, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable or physiologically acceptable diluents, carriers or excipients. In certain embodiments, etrumadenant, or a pharmaceutically acceptable salt thereof, is present in a therapeutically effective amount. The pharmaceutical compositions may be administered ex vivo or in vivo. Furthermore, the pharmaceutical compositions can be formulated to be compatible with the intended method or route of administration; exemplary routes of administration are set forth herein. Furthermore, the pharmaceutical compositions may be used in combination with other therapeutically active agents or compounds to treat or prevent the diseases, disorders, and conditions as contemplated by the present disclosure (e.g., cancer). [0069] The pharmaceutical compositions include etrumadenant, or a pharmaceutically acceptable salt thereof. The pharmaceutical composition may optionally include one or more compounds selected from Compound (d), Compound (f), and Compound (g), but in some embodiments, is substantially free of one or more compounds selected from Compound (d), Compound (f), and Compound (g). For instance, in one embodiment, the pharmaceutical composition is substantially free of Compound (d). In another embodiment, the pharmaceutical composition is substantially free of Compound (f). In another embodiment, the pharmaceutical composition is substantially free of Compound (g). In some embodiments, the pharmaceutical composition is substantially free of Compound (d) and Compound (f). In some embodiments, the pharmaceutical composition is substantially free of Compound (d) and Compound (g). In some embodiments, the pharmaceutical composition is substantially free of Compound (f) and Compound (g). In other embodiments, the pharmaceutical composition is substantially free of Compound (d), Compound (f), and Compound (g). [0070] The pharmaceutical compositions containing etrumadenant may be in a form suitable for oral use, for example, as tablets, capsules, troches, lozenges, aqueous or oily suspensions, dispersible powders or granules, emulsions, hard or soft capsules, or syrups, solutions, microbeads or elixirs. Pharmaceutical compositions intended for oral use may be prepared according to any method known to the art for the manufacture of pharmaceutical compositions, and such P0043-WO-PCT/P0043-WO 37JD-350579-WO compositions may contain one or more agents, such as, for example, sweetening agents, flavoring agents, coloring agents, and preserving agents in order to provide pharmaceutically elegant and palatable preparations. Tablets, capsules, and the like contain the active ingredient in admixture with non-toxic pharmaceutically acceptable excipients which are suitable for the manufacture of tablets. These excipients may be, for example, diluents, such as calcium carbonate, sodium carbonate, lactose, calcium phosphate, microcrystalline cellulose, mannitol, or sodium phosphate; granulating and disintegrating agents, for example, corn starch, croscarmellose sodium, or alginic acid; binding agents, for example, starch, gelatin, or acacia; lubricating agents, for example, magnesium stearate, sodium stearyl fumarate, stearic acid, or talc; and glidants, for example, colloidal silica. [0071] In various embodiments, the pharmaceutical composition includes one or more polymers. In some embodiments, the one or more polymers are independently selected from hydroxypropylmethylcellulose acetate succinate (HPMCAS), copovidone (PVP-VA), cellulose acetate phthalate (CAP), hydroxypropyl methylcellulose E3 (HPMC E3), hydroxypropyl methylcellulose phthalate (HPMCP), polyvinylpyrrolidone (PVP), and polyvinyl caprolactam– polyvinyl acetate–polyethylene glycol graft copolymer. [0072] In some embodiments, the composition is a tablet. In one or more embodiments, the pharmaceutical composition is a tablet comprising one or more fillers, disintegrants, glidants, lubricants, and polymers. In some embodiments, the fillers are selected from microcrystalline cellulose, mannitol, or combinations thereof. In some embodiments, the disintegrant is croscarmellose sodium. In some embodiments, the glidant is colloidal silica. In some embodiments, the lubricant is sodium stearyl fumarate. In some embodiments, the polymer is hydroxypropylmethylcellulose acetate succinate (HPMCAS). [0073] The tablets, capsules, and the like suitable for oral administration may be uncoated or coated by known techniques to delay disintegration and absorption in the gastrointestinal tract and thereby provide a sustained action. For example, a time-delay material such as glyceryl monostearate or glyceryl distearate may be employed. They may also be coated by techniques known in the art to form osmotic therapeutic tablets for controlled release. Additional agents include biodegradable or biocompatible particles or a polymeric substance such as polyesters, polyamine acids, hydrogel, polyvinyl pyrrolidone, polyanhydrides, polyglycolic acid, ethylene- vinylacetate, methylcellulose, carboxymethylcellulose, protamine sulfate, or lactide/glycolide copolymers, P0043-WO-PCT/P0043-WO 37JD-350579-WO polylactide/glycolide copolymers, or ethylenevinylacetate copolymers in order to control delivery of an administered composition. For example, the oral agent can be entrapped in microcapsules prepared by coacervation techniques or by interfacial polymerization, by the use of hydroxymethylcellulose or gelatin-microcapsules or poly (methylmethacrolate) microcapsules, respectively, or in a colloid drug delivery system. Colloidal dispersion systems include macromolecule complexes, nano-capsules, microspheres, microbeads, and lipid-based systems, including oil-in-water emulsions, micelles, mixed micelles, and liposomes. Methods for the preparation of the above-mentioned formulations will be apparent to those skilled in the art. [0074] Formulations for oral use may also be presented as hard gelatin capsules wherein the active ingredient is mixed with an inert solid diluent, for example, calcium carbonate, calcium phosphate, kaolin or microcrystalline cellulose, or as soft gelatin capsules wherein the active ingredient is mixed with water or an oil medium, for example, peanut oil, liquid paraffin, or olive oil. [0075] The pharmaceutical compositions typically comprise a therapeutically effective amount of etrumadenant and/or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically and physiologically acceptable formulation agents. Suitable pharmaceutically acceptable or physiologically acceptable diluents, carriers, or excipients include, but are not limited to, antioxidants (e.g., ascorbic acid and sodium bisulfate), preservatives (e.g., benzyl alcohol, methyl parabens, ethyl or n-propyl, p-hydroxybenzoate), emulsifying agents, suspending agents, dispersing agents, solvents, fillers, bulking agents, detergents, buffers, vehicles, diluents, lubricants, and/or adjuvants. [0076] The pharmaceutical compositions of the present disclosure may be administered to a subject in an amount that is dependent upon, for example, the goal of administration (e.g., the degree of resolution desired); the age, weight, sex, and health and physical condition of the subject to which the formulation is being administered; the route of administration; and the nature of the disease, disorder, condition, or symptom thereof. The dosing regimen may also take into consideration the existence, nature, and extent of any adverse effects associated with the agent(s) being administered. Effective dosage amounts and dosage regimens can readily be determined from, for example, safety and dose-escalation trials, and in vivo studies (e.g., animal models). P0043-WO-PCT/P0043-WO 37JD-350579-WO [0077] For oral administration of a pharmaceutical composition according to the instant disclosure, the compositions can be provided in the form of tablets, capsules and the like containing from 1 to 1000 milligrams of the etrumadenant, or a pharmaceutically acceptable salt thereof, particularly 1, 3, 5, 10, 15, 20, 25, 50, 75, 100, 150, 200, 250, 300, 400, 500, 600, 750, 800, 900, and 1000 milligrams of the etrumadenant, or pharmaceutically acceptable salt thereof. [0078] In certain embodiments, the dosage of the desired etrumadenant or a pharmaceutically acceptable salt thereof is contained in a “unit dosage form.” The phrase “unit dosage form” refers to physically discrete units, each unit containing a predetermined amount of the etrumadenant, or a pharmaceutically acceptable salt thereof, either alone or in combination with one or more additional agents, sufficient to produce the desired effect. IV. Process for Preparing Compounds of Formula (IIa-i) and (IIa-ii) [0079] As previously noted, the instant disclosure relates to processes for preparing azolopyrimidines, or a pharmaceutically acceptable salt thereof. The compound of Formula (IIa-i) and the compound of Formula (IIa-ii) have been found to be useful in the manufacture of azolopyrimidines and pharmaceutically acceptable salts thereof. Utilization of these compounds during the manufacturing of azolopyrimidines provides greater yields and purity. In particular, methods for preparing etrumadenant, or a pharmaceutically acceptable salt thereof, that employ the compound of Formula (IIa-i) and the compound of Formula (IIa-ii) significantly reduce or eliminate impurities from contaminating etrumadenant, or a pharmaceutically acceptable salt thereof. The structure of the compound of Formula (IIa-i) and the compound of Formula (IIa-ii) are provided below. X is Formula (IIa-i) Formula (IIa-ii) [0080] The instant disclosure is directed to processes for preparing a compound of Formula (IIa-i) and a compound of Formula (IIa-ii). In one embodiment, a process for preparing a compound of Formula (IIa-i) comprises: P0043-WO-PCT/P0043-WO 37JD-350579-WO (a) contacting a compound of Formula (III) with a halogenation reagent to form a compound of Formula (IV): wherein is a C1-C6 alkyl, and X is a halo; (b) contacting the compound of Formula (IV) with a methyl magnesium Grignard reagent to form a compound of Formula (II); and (c) contacting the compound of Formula (II) with an acid to form the compound of Formula (IIa-i). [0081] In various embodiments, R ¹ of Formula (III) and Formula (IV) is a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, or a tert-butyl group. In further embodiments, R ¹ of Formula (III) and Formula (IV) is a methyl group, an ethyl group, a propyl group, or an isopropyl group. In one embodiment, R ¹ of Formula (III) and Formula (IV) is a methyl group. In some embodiments, X is chloro. [0082] Nonlimiting examples of useful methyl magnesium Grignard reagents include methyl magnesium fluoride, methyl magnesium chloride, methyl magnesium bromide, and methyl magnesium iodide. [0083] The halogenation reagent may be a bromination reagent, an iodination reagent, or a chlorination reagent. Nonlimiting examples of bromination reagents include, but are not limited to, bromine, hydrobromic acid, carbon tetrabromide, phosphorus tribromide, and potassium bromide. Nonlimiting examples of iodination reagents include, but are not limited to, hydroiodic acid, iodine, carbon tetraiodide, phosphorus triiodide, sodium iodide, and potassium iodide. Nonlimiting P0043-WO-PCT/P0043-WO 37JD-350579-WO examples of chlorination reagents include, but are not limited to, carbon tetrachloride, methanesulfonyl chloride, sulfuryl chloride, thionyl chloride, cyanuric chloride, N- chlorosuccinateimide, phosphorus oxychloride (V), phosphorus pentachloride, and phosphorus trichloride. In certain embodiments, the chlorination reagent is thionyl chloride. [0084] In some embodiments, the halogenation reagent is selected from pyridinium poly(hydrogen fluoride), thionyl fluoride, carbon tetrachloride, methanesulfonyl chloride, sulfuryl chloride, thionyl chloride, cyanuric chloride, N-chlorosuccinateimide, phosphorus oxychloride (V), phosphorus pentachloride, phosphorus trichloride, hydrobromic acid, carbon tetrabromide, phosphorus tribromide, potassium bromide, hydroiodic acid, thionyl bromide, carbon tetraiodide, phosphorus triiodide, sodium iodide, potassium iodide, and thionyl iodide. In one embodiment, the halogenation reagent is thionyl chloride (SOCl ₂ ). [0085] In some embodiments, the acid is methanesulfonic acid, benzenesulfonic acid, DL- camphorsulfonic acid, ethanesulfonic acid, naphthalene sulfonic acid, p-toluenesulfonic acid, hydrochloric acid, phosphoric acid, or sulfuric acid. In some embodiments, the acid is methanesulfonic acid, benzenesulfonic acid, or DL-camphoric acid. In one embodiment, the acid is methanesulfonic acid. [0086] In various embodiments, the conversion of (a) is carried out in a solvent comprising methyl acetate. In various embodiments, the conversion of (b) is carried out in a solvent comprising THF. [0087] In some embodiments, X is chloro and R ¹ is methyl. [0088] In various embodiments, a process comprises contacting a compound of Formula (IIa-i) with a base to form the compound of Formula (II), wherein X is a halo and A is a counterion. Nonlimiting examples of useful counterions include methanesulfonate, benzenesulfonate, DL- camphorsulfonate, ethanesulfonate, naphthalene sulfonate, p-toluenesulfonate, hydrochlorate, phosphate, and sulfate. In one embodiment, the counterion is selected from methanesulfonate, benzenesulfonate, and DL-camphorsulfonate. In one embodiment, the counterion is methanesulfonate. P0043-WO-PCT/P0043-WO 37JD-350579-WO [0089] for example, bases selected from metal hydroxides, carbonates, phosphates, tertiary amines, and aryl amines, such as potassium bicarbonate, sodium bicarbonate, sodium carbonate, potassium carbonate, cesium carbonate, potassium fluoride, potassium phosphate dibasic, potassium phosphate tribasic, sodium hydroxide, potassium hydroxide, dicyclohexylamine, N-methylmorpholine, and triethylamine. In one embodiment, the base is sodium hydroxide, ammonium hydroxide, or a combination thereof. In one embodiment, the base is sodium hydroxide. [0090] In a further embodiment, the process described above further comprises contacting a compound of Formula (II) with an azide salt to form Compound (16): [0091] Nonlimiting examples of azide salts include sodium azide, potassium azide, lithium azide, and cesium azide. In one embodiment, the azide salt is sodium azide. V. Characterization of Compound (IIa-ii) [0092] In one aspect, the instant disclosure is drawn to a compound of Formula (II-ai): wherein X is halo; and A is a counter anion. P0043-WO-PCT/P0043-WO 37JD-350579-WO [0093] In some embodiments, X is fluoro, chloro, bromo, or iodo. In some embodiments, X is fluoro, chloro, or bromo. In one embodiment, X is chloro. [0094] In some embodiments, A is methanesulfonate, benzenesulfonate, DL-camphorsulfonate, ethanesulfonate, naphthalene sulfonate, p-toluenesulfonate, or chloride. In some embodiments, A (the counter anion) is methanesulfonate, benzenesulfonate, or DL-camphorsulfonate. In one embodiment, the counter anion is methanesulfonate. [0095] In one or more embodiments, the compound of Formula (IIa-i) has a structure according to Formula (IIa-ii) (OMs = mesylate): ii). [0096] In some embodiments, the compound of Formula (IIa-ii) is in a solid form. In some embodiments, the compound of Formula (IIa-ii) is in an amorphous form. In some embodiments, the Compound of Formula (IIa-ii) is in a crystalline form. [0097] In one embodiment, the crystalline form of the compound of Formula (IIa-ii) has one or more X-ray powder diffraction signals at 2θ values obtained with CuKα1-radiation of 18.7±0.2, 22.6±0.2, 23.3±0.2, and 28.1±0.2. In one embodiment, the crystalline form of the compound of Formula (IIa-ii) has one or more X-ray powder diffraction signals at 2θ values obtained with CuKα1- radiation of 18.7±0.1, 22.6±0.1, 23.3±0.1, and 28.1±0.1. [0098] In a further embodiment, the crystalline form of the compound of Formula (IIa-ii) is characterized by one or more X-ray powder diffraction signals at 2θ values obtained with CuKα1- radiation of 18.7±0.2, 22.6±0.2, 23.3±0.2, and 28.1±0.2. In some embodiments, the crystalline form of the compound of Formula (IIa-ii) is characterized by one or more X-ray powder diffraction signals at 2θ values obtained with CuKα1-radiation of 18.7±0.1, 22.6±0.1, 23.3±0.1, and 28.1±0.1. [0099] In another embodiment, the crystalline form of the compound of Formula (IIa-ii) is characterized by two or more X-ray powder diffraction signals at 2θ values obtained with CuKα1- P0043-WO-PCT/P0043-WO 37JD-350579-WO radiation of 18.7±0.2, 22.6±0.2, 23.3±0.2, and 28.0±0.2. In some embodiments, the crystalline form of the compound of Formula (IIa-ii) is characterized by two or more X-ray powder diffraction signals at 2θ values obtained with CuKα1-radiation of 18.7±0.1, 22.6±0.1, 23.3±0.1, and 28.1±0.1. [0100] In another embodiment, the crystalline form of the compound of Formula (IIa-ii) is characterized by three or more X-ray powder diffraction signals at 2θ values obtained with CuKα1- radiation of 18.7±0.2, 22.6±0.2, 23.3±0.2, and 28.1±0.2. In some embodiments, the crystalline form of the compound of Formula (IIa-ii) is characterized by three or more X-ray powder diffraction signals at 2θ values obtained with CuKα1-radiation of 18.7±0.1, 22.6±0.1, 23.3±0.1, and 28.1±0.1. [0101] In another embodiment, the crystalline form of the compound of Formula (IIa-ii) is characterized by X-ray powder diffraction signals at 2θ values obtained with CuKα1-radiation of 18.7±0.2, 22.6±0.2, 23.3±0.2, and 28.0±0.2. In some embodiments, the crystalline form of the compound of Formula (IIa-ii) is characterized by X-ray powder diffraction signals at 2θ values obtained with CuKα1-radiation of 18.7±0.1, 22.6±0.1, 23.3±0.1, and 28.1±0.1. [0102] The crystalline form of the compound of Formula (IIa-ii) may be further characterized by one or more signals at 2θ values obtained with CuKα1-radiation at 9.4±0.2, 14.5±0.2, 15.8±0.2, 18.9±0.2, 21.9±0.2, and 22.1±0.2. In some embodiments, the crystalline form of the compound of Formula (IIa-ii) may be further characterized by one or more signals at 2θ values obtained with CuKα1-radiation at 9.4±0.1, 14.5±0.1, 15.8±0.1, 18.9±0.1, 21.9±0.1, and 22.1±0.1. [0103] In some embodiments, the crystalline compound of Formula (IIa-ii) is characterized by a DVS isotherm characterized by a change in mass of between about 20% to about 30% between about 40% relative humidity (RH) and about 70% RH. In some embodiments, the crystalline compound of Formula (IIa-ii) is characterized by a DVS isotherm characterized by a change in mass of about 25% between about 40% RH and about 70% RH. In some embodiments, the crystalline compound of Formula (IIa-ii) is characterized by a DVS isotherm substantially in accordance with FIG. 6. VI. Process for Preparing Etrumadenant with Improved Impurity Profile [0104] The instant disclosure also describes a useful process for preparing azolopyrimidines, or a pharmaceutically acceptable salt thereof, especially etrumadenant, or a pharmaceutically P0043-WO-PCT/P0043-WO 37JD-350579-WO acceptable salt thereof, or a composition comprising etrumadenant, or a pharmaceutically acceptable salt thereof, having an improved impurity profile. The process comprises: (a) contacting a compound of Formula (II) with an azide salt to form Compound (16): (b) combining Compound (16) and Compound (8) with a copper catalyst to form etrumadenant: [0105] In Formula (II), X is a halo. In some embodiments, X is fluoro, chloro, or bromo. In one embodiment, X is chloro. [0106] Nonlimiting examples of azide salts include sodium azide, potassium azide, lithium azide, and cesium azide. In some embodiments, the azide salt is sodium azide. [0107] Examples of useful copper catalysts include zero-valent, monovalent or divalent copper catalysts and complexes thereof, such as copper, copper (I) chloride, copper (I) bromide, copper (I) iodide, copper (I) trifluoromethanesulfonate, a copper (I) bromide-dimethyl sulfide complex, copper (II) bromide, copper (II) acetate, copper (II) sulfate, and copper (II) acetate. Nonlimiting examples include copper(II) trifluoromethanesulfonate (Cu(OSO₂CF₃)₂), copper(II) carbonate basic (CuCO3*Cu(OH)2), copper(I) trifluoromethanesulfonate toluene complex (CuOTf *toluene), tetrakisacetonitrile copper(I) triflate ((CH3CN)4CuOTf), ammonium tetrachlorocuprate(II), copper benzene- 1,3,5- tricarboxylate, bis(1,3-bis(2,6-diisopropylphenmidazolezol-2-ylidene)copper( I) tetrafluoroborate, bis[1,3-bis(2,4,6-trimethylphenmidazolezol-2-ylidene]copper( I) tetrafluoroborate, bis(ethylenediamine) copper(II)hydroxide, (R,R)-(-)-’,N'-bis(3- hydroxylsalicylidene)-l,2- cyclohexanediaminocopper(II) samarium isopropoxide, P0043-WO-PCT/P0043-WO 37JD-350579-WO bis[(tetrabutylammonium iodide)copper(I) iodide], [bis(trimethylsilyl)acetylene] (hexafluoroacetylacetonato) copper(I), bromotris(triphenylphosphine)copper(I), 5- chlorobenzo[b]phosphindole, chloro[l,3-bis(2,6- diisopropylphenmidazolezol-2-ylidene]copper(I), copper(I) acetate, copper(II) acetate 1,2- bis(diphenylphosphino)ethane, copper(II) acetylacetonate, copper(I) bromide, copper(I) bromide dimethyl sulfide complex, copper(II) tert-butylacetoacetate, copper(II) carbonate, copper(I) chloride, copper(II) chloride, copper(I) chloride-bis(lithium chloride) complex, copper(I) cyanide di(lithium chloride) complex, copper(II) 3,5- diisopropylsalicylate, copper (I) diphenylphosphinate, copper(II) ethylacetoacetate, copper(II) 2- ethylhexanoate, copper formate, copper hydride, copper(I) iodide, copper iodide dimethyl sulfide complex, copper(I) iodide trimethylphosphite complex, copper(I) 3-methylsalicylate, copper(II) nitrate, copper(I) oxide, copper oxychloride, copper(II) sulfate, copper(II) tartrate, copper(II) tetrafluoroborate, copper(I) thiophene-2-carboxylate, copper(I) thiophenolate, di-hydroxo- bis[(N,’,N’,N'- tetramethylethylenediamine)copper(II)] chloride, copper(I) trifluoromethanesulfonate benzene complex, cupric carbonate, {cuprous 2-[(2- diphenylphosphino)benzylideneamino]-3,3- dimethylbutyrate,triflatesodium triflate} complex, (l,4- diazabicyclo[2.2.2]octane)copper(I) chloride complex, dichloro(l,10-phenanthroline)copper(II), dilithium tetrachlorocuprate(II), hydro[(4R)-[’,4'-bi-l,3-benzodioxole]-’,5'-diylbis[bis[3 ,5-bis(l,l- dimethylethyl)-4- methoxyphenyl] phosphine-P] ] copper (I) , (ethylcyclopentadienyl) (triphenylphosphine)copper (I), fluorotris(triphenylphosphine)copper(I), iodo(triethyl phosphite)copper(I), mesitylcopper(I), (l,10-phenanthroline)bis(triphenylphosphine)copper(I) nitrate dichloromethane adduct, phthalocyanine green, tetrakis(acetonitrile)copper(I) hexafluorophosphate, tetrakis(acetonitrile)copper(I) tetrafluoroborate, and tetrakis(pyridine)copper(II) triflate. [0108] In one embodiment, the copper catalyst is selected from copper (II) sulfate (CuSO ₄ ) or hydrates thereof (e.g., CuSO4*nH2O, wherein n is an integer from 1-7), copper (I) iodide (CuI), copper (I) bromide (CuBr), tetrakisacetonitrile copper(I) trifluoromethanesulfonate ((CH ₃ CN) ₄ CuOTf), copper (II) acetate (Cu(CH ₃ COO) ₂ ), copper(II) trifluoromethanesulfonate (Cu(OTf)2), copper(II) carbonate basic (CuCO3*Cu(OH)2), copper(I) trifluoromethanesulfonate toluene (CuOTf *toluene), tetrakis(acetonitrile)copper(I) hexafluorophosphate ([Cu(CH₃CN)₄]PF₆), tetrakis(acetonitrile)copper(I) tetrafluoroborate ([Cu(CH₃CN)₄]PF₆), and tetrakis(pyridine)copper(II) triflate ([Cu(OTf) ₂ (py) ₄ ]). In some embodiments, the copper catalyst is P0043-WO-PCT/P0043-WO 37JD-350579-WO selected from tetrakisacetonitrile copper(I) triflate ((CH ₃ CN) ₄ CuOTf), copper(II) trifluoromethanesulfonate (Cu(OTf)2), copper(II) carbonate basic (CuCO3*Cu(OH)2), copper(I) trifluoromethanesulfonate toluene (CuOTf *toluene), tetrakis(acetonitrile)copper(I) hexafluorophosphate ([Cu(CH₃CN)₄]PF₆), tetrakis(acetonitrile)copper(I) tetrafluoroborate ([Cu(CH₃CN)₄]PF₆), tetrakis(pyridine)copper(II) triflate ([Cu(OTf)2(py)4]), copper (II) acetate (Cu(CH3COO)2), and copper (II) sulfate (CuSO4), or a hydrate thereof. [0109] In one embodiment, the copper catalyst is tetrakisacetonitrile copper(I) trifluoromethanesulfonate ((CH3CN)4CuOTf). In one embodiment, the copper catalyst is copper (II) acetate (Cu(CH3COO)2). In one embodiment, the copper catalyst is copper (II) sulfate (CuSO4) or a hydrate thereof. [0110] In a further embodiment, a compound of Formula (II), wherein X is chloro (Compound (13)), may be prepared by contacting the compound of Formula (IIa-ii) with a base to form Compound (13): . [0111] Nonlimiting or bases, for example, bases selected from metal hydroxides, carbonates, phosphates, tertiary amines, and aryl amines, such as potassium bicarbonate, sodium bicarbonate, sodium carbonate, potassium carbonate, cesium carbonate, potassium fluoride, potassium phosphate dibasic, potassium phosphate tribasic, sodium hydroxide, potassium hydroxide, dicyclohexylamine, N-methylmorpholine, and triethylamine. In some embodiments, the base is sodium hydroxide, ammonium hydroxide, or a combination thereof. In one embodiment, the base is sodium hydroxide. [0112] In a further embodiment, Compound (8) may be obtained by contacting a compound of Formula (V) with a desilylation agent in the presence of a buffering agent: P0043-WO-PCT/P0043-WO 37JD-350579-WO NH ₂ NH ₂ N N Me N N Me CN wherein PG is an [0113] In some embodiments, the alkyne protecting group is a silane, e.g., trimethylsilyl (TMS), triethylsilyl (TES), triisopropylsilyl (TIPS), tert-butylmethylsilyl (TBS or TBDMS), and tert- butyldiphenylsilyl (TBDPS). In some embodiments, the protecting group is triisopropylsilyl (TIPS). [0114] Nonlimiting examples of desilylation agents include ammonia, aqueous sodium hydroxide solution, potassium carbonate, dilute hydrochloric acid, dilute sulfuric acid, dilute trifluoroacetic acid or acetic acid, tetramethylammonium hydroxide, tetrabutylammonium hydroxide, tetrahexylammonium hydroxide, tetraoctylammonium hydroxide, phenyltrimethylammonium hydroxide, (3-trifluoro methylphenyl) trimethylammonium hydroxide and (2-hydroxyethyl) trimethylammonium hydroxide (so-called “choline”). In some embodiments, the desilylation agent is tetrabutylammonium hydroxide (TBAH). [0115] Nonlimiting examples of buffering agents include K2HPO4, KH2PO4, H3PO4, and combinations thereof. In one embodiment, the buffering agent is H3PO4. Nonlimiting examples of solvents include THF, water, and combinations thereof. In some embodiments, the conversion is carried out in a solvent comprising THF, water, or a combination thereof. EXAMPLES [0116] The following examples are put forth to provide those of ordinary skill in the art with a complete disclosure and description of how to make and use what is disclosed in the present disclosure and are not intended to limit the scope of what the inventors regard as their disclosure. Additional compounds within the scope of this disclosure may be made using methods based on those illustrated in these examples, or based on other methods known in the art. Efforts have been made to ensure accuracy with respect to numbers used (e.g., amounts, temperature, etc.), but some experimental errors and deviations should be accounted for. P0043-WO-PCT/P0043-WO 37JD-350579-WO [0117] ¹ H NMR spectra were recorded on a Bruker BioSpin Ascend 400 MHz NMR spectrometer equipped with 54 mm Long Hold Time Magnet, or a Varian 400 MHz NMR spectrometer. Analytical HPLC was performed on an Agilent 1200 series HPLC system with UV detector or equivlent. The HPLC was equipped with a GL Sciences Inertsil ODS-3 (150mm×4.6mm, 3.0 µm) column, XBridge C18, 150 mm x 4.6 mm, 3.5μm column, XBridge BEH C18, 75 mm x 4.6 mm, 2.5 μm column, or ACE Excel 3 C18-PFP, 150 mm x 4.6 mm, 3 μm column. [0118] Unless indicated otherwise, temperature is in degrees Celsius (° C), and pressure is at or near atmospheric. Standard abbreviations are used, including the following: rt or r.t.=room temperature; min=minute(s); h or hr=hour(s); ng=nanogram; μg=microgram; mg=milligram; g=gram; kg=kilogram; μl or μL=microliter; ml or mL=milliliter; l or L=liter; μM=micromolar; mM=millimolar; M=molar; mol=mole; mmol=millimole; aq.=aqueous; calcd=calculated; sat. or satd. = saturated; equiv. = equivalent(s); psi = pounds per square inch; MHz=megahertz; Hz=hertz; ppm=parts per million; ESI MS = electrospray ionization mass spectrometry; NMR=nuclear magnetic resonance; TLC = thin layer chromatography; LCMS = liquid chromatography-mass spectrometry; HPLC = high-performance liquid chromatography; IPC = ion pair chromatography; LCAP = liquid chromatography area percent; %-a/a = area percent; %-w/w = weight percent; MeOH = methanol; EtOH = ethanol; n-BuOH = n-butanol; iPAc = isopropyl acetate; MeOAc = methyl acetate; EDTA = ethylenediaminetetraacetic acid; EtOAc = ethyl acetate; MEK = methylethylketone; THF = tetrahydrofuran; Me-THF = 2-methyltetrahydrofuran; MTBE = methyl tert-butyl ether; MsOH = methanesulfonic acid; TBABr = tetrabutylammonium bromide; K ₄ [Fe(CN) ₆ ]•3H ₂ O = potassium hexacyanoferrate (II) trihydrate; QPhos = pentaphenyl(di-tert- butylphosphino)ferrocene; XPhos = IUPAC: dicyclohexyl[2′,4′,6′-tris(propan-2-yl)[1,1′-bipheny l]- 2-yl]phosphane; tBu-XPhos = IUPAC: bis(2-methyl-2-propanyl)(2',4',6'-triisopropyl-2- biphenylyl)phosphine; sSPhos = IUPAC: sodium 2′-dicyclohexylphosphino-2,6-dimethoxy-1,1′- biphenyl-3-sulfonate hydrate; and Catacxium PtB = n-Phenyl-2-(di-tert-butylphosphino)pyrrole, N- Phenylpyrrol-2-yldi-tert-butylphosphine. P0043-WO-PCT/P0043-WO 37JD-350579-WO Example 1: Cyanation of Aryl Bromide 1) SOCl ₂ B ^r _CO2H 2) NH ₃ OH ^Br _CN iPrMgCl ^HO ₂ ^C _CN [0119] The first-generation route to synthesize etrumadenant employed 3-bromo-2- methylbenzoic acid (Compound (1)) as a key starting material (Scheme 1). Subsequent amidation and dehydration afforded the corresponding nitrile (Compound (2)), which was further functionalized by bromine/magnesium exchange and trapping with carbon dioxide to form the corresponding carboxylic acid (Compound (3)). In an effort to reduce costs, improve efficiency, and reduce the total number of steps to obtain etrumadenant, the palladium catalyzed cyanation of aryl bromide (Compound (1)) was explored (Scheme 2). Scheme 2 [0120] Reactions performed on micromole scale were carried out to identify an air-stable palladium catalyst for the transformation. Briefly, a number of bulky phosphine ligands, including QPhos, XPhos, tBu-XPhos, sSPhos, and Catacxium PtB, were tested with [Pd(C ₃ H ₅ )Cl] ₂ in a micromole scale cyanation of Compound (1) to form Compound (3) using potassium ferrocyanide as a cyanide source (Scheme 2). From these small-scale reactions, it was observed that the use of all ligands resulted in high conversion and good product purity. The results from these reactions are summarized in Table 1 below. P0043-WO-PCT/P0043-WO 37JD-350579-WO Table 1 Excerpt from Micromole Scale Catalytic Cyanation Ligand Screening y [0121] p g . , . os, 1.2 equiv K2CO3, 95°C, n-butanol / water) gave full conversion but a significant increase in the formation of the des-bromo impurity (Compound (a) (Scheme 3). A study of the reaction kinetics and purity profile as a function of temperature allowed for definition of a temperature window (80°C ± 5°C to 85°C ± 5°C) where conversion could be achieved with an acceptable level of des-bromo impurity (Compound (a)). Scheme 3 Table 2 ) [0122] A survey of the production costs in preparation for a larger scale campaign to an advanced intermediate in the etrumadenant synthesis singled out Palladium as the highest material cost contributor, leading to a drive to reduce the catalyst loading further from 0.5%. However, initial attempts to reduce catalyst loading led to a drop in reproducibility below 0.4 mol% [Pd(C3H5)Cl]2 P0043-WO-PCT/P0043-WO 37JD-350579-WO with conversions ranging between 1-100%. Variable conversion at lower catalyst loading was attributed to the initial mix of Palladium pre-catalyst and ligand to form the active catalyst. [0123] Two strategies were identified targeting efficient formation of the active catalyst: 1) addition of trace water; and 2) heating the mixture of the catalyst components in 5 volumes of neat n-butanol (with respect to starting material). Specifically, for the first strategy, when the catalyst pre-mix was run at room temperature in n-butanol spiked with no less than 1000 ppm water, full conversion of the subsequent cyanation reaction was consistently achieved at loadings as low as 0.13 mol% (Table 3). Table 3 Impact of Catalyst Loading on Reaction Conversion with F >1000 ppm prior . B: Catalyst components mixed at 75°C, 30 min and cooled to 23°C prior to combining with starting material. [0124] Further, for the second strategy, it was found that the temperature and duration of heating during the pre-mix had an impact on the cyanation reaction conversion, with a limit of no more than 70 min ≥ 65°C giving full conversion (Table 4).

P0043-WO-PCT/P0043-WO 37JD-350579-WO Table 4 Impact of Catalyst Pre-activation Heating Time on b y chanical agitation. perature of 70-80°C. [0125] Both pre-activation methods enabled lower catalyst loadings, with full conversion achieved at 0.13 mol% [Pd(C3H5)Cl]2 after 18 h at 80°C. [0126] A three-batch scale-up campaign incorporating the process improvements to the cyanation step gave consistently high performance (Table 5). Full conversion was observed with 0.25 mol% [Pd(C3H5)Cl]2 after 24 h elapsed at 80°C by employing the heated catalyst pre-mix. Hydro-debromo impurity (Compound (a)) ranged from 0.12-0.14 area% in process. The process mass intensity of the workup was improved by implementing a quench for residual cyanide species with FeCl3, resulting in the precipitation of the putative Fe4[Fe(CN)6]3. Filtration, aqueous workup, and crystallization from isopropyl alcohol (IPA)/water afforded the product in 91.8% average yield, 99.9% purity with <100 ppm residual Pd. Scheme 4 P0043-WO-PCT/P0043-WO 37JD-350579-WO Table 5 Results from Scale-up of Second Generation Cyanation Process d p g p p [0127] To a 2500 L glass lined vessel was added water (915 kg) and K2CO3 (141 kg), and the contents sparged with N2 for about 0.5-1 h. Starting material (Compound (1)) (183 kg) was added as a solid and the mixture stirred for about 0.5-2 h at about 20-30°C until all the solid dissolved during which off-gassing was observed. To a 5000 L glass lined vessel was added n-butanol (741 kg), which was sparged with N2 for about 1-2 h. [Pd(C3H5)Cl]2 (0.815 kg) and XPhos (2.15 kg) were added to the reactor under N ₂ protection. The reaction mass was warmed to about 75°C over 2 h, stirred for about 0.5 h at about 75°C, and then cooled to about 25°C over 2 h. The starting material solution was charged to the reactor under N2 protection. K4[Fe(CN)6]•3H2O (180 kg, 0.5 equiv) was charged to the reactor under N ₂ protection. The resultant slurry was sparged with N ₂ for about 0.5- 1 h. The reaction mass was warmed to about 80°C over 3 h, then stirred for about 24 h at about 80°C under N2 protection. After IPC by HPLC indicated the reaction was complete, the slurry was cooled to about 30°C, filtered, and rinsed forward with n-butanol (293 kg). The filtrate was distilled in a solvent exchange with portion wise addition of water (3200 kg) over approximately 48 h. To the aqueous product solution was charged FeCl3 (11 kg) to a final pH of 8.5. The solution was stirred at about 15°C for about 0.5-1 h until residual cyanide was found to be ≤ 5 ppm, filtered through diatomaceous earth, and rinsed forward with 366 kg water. Me-THF (1739 kg) was charged to aqueous product solution, and the pH adjusted with 182 kg of 35% HCl to 0-2. The phases were separated and the organic product solution washed with 10% Na2SO4 solution (1098 kg). The organic product solution was concentrated with portion wise addition of IPA (2196 kg) at an internal temperature and pressure below about 50°C and -0.09 MPa during which product spontaneously crystallized. The solution was warmed to about 65 ^°C and water (2562 kg) was charged. The mixture was linearly ramped to about 25°C over 4 h and filtered by centrifuge. The product wetcake was washed with 1:3.5 v/v IPA/water (384 kg) in three portions and dried at about 60°C and -0.09 MPa P0043-WO-PCT/P0043-WO 37JD-350579-WO for about 25 h in a double cone dryer to afford 124 kg Compound (3) (90.4% yield) as an off-white crystalline solid with 99.85%-a/a purity, 100.3 wt% assay, <100 ppm Pd and 105 ppm Fe. Example 3: Synthesis of Compound (16) from Compound (9) [0128] The initial preparation Compound (9) demonstrated certain limitations, including low selectivity and the formation of impurities, including reactive impurities. Removal of the impurities after the reaction had a negative impact on yield and process efficiency. Accordingly, different routes to access Compound (16) were investigated as shown in Scheme 5 below. [0129] To avoid precipitation of magnesium salts, reverse addition of Compound (9) to methyl magnesium chloride (MeMgCl) was investigated. Reverse addition (C), and regular addition (D) were compared in a side-by-side experiment on a 0.5 g scale. The results are shown in Table 6. P0043-WO-PCT/P0043-WO 37JD-350579-WO Table 6 Comparison of Dosage Order of MeMgCl and Compound (9) [0 30] xper ment C s owed an mproved react on pro e over xper ment . eact on C was quenched on ammonium citrate which showed fast and clean separation of layers. Both layers were homogenous. [0131] The reaction according to Experiment C was repeated on a 5 g scale. The product oil (Compound (12)) was dissolved in MTBE and dried over sodium sulfate. Upon removal of the volatiles, pale yellow oil (3.85 g) was obtained. Quantitative NMR carried out by dissolution of product and a suitable internal standard in deuterated solvent and analyzed by 1H NMR revealed 82%-w/w product content, corresponding to 63% theoretical yield. The main observed impurity was the corresponding hydroxymethyl ketone 1-(6-(hydroxymethyl)pyridin-2-yl)ethan-1-one (Compound (b)) (approximately 13%-w/w). [0132] The reaction was further repeated and monitored by IPC after extended stirring at temperatures shown in Table 7. The IPC sample was diluted and analyzed by IPC against reference standards for Compound (9) and Compound (12).

P0043-WO-PCT/P0043-WO 37JD-350579-WO Table 7 Results of IPC After Extended Stirring at Various Temperatures t [0133] By adding Compound (9) to MeMgCl at an internal temperature of 0-5 °C, IPC purity could be further improved. The product could be isolated as a mixture with Compound (b) (approx. 9:1 Compound (12): Compound (b)). [0134] Conversion of Compound (12) to a Compound of Formula (II) was attempted in a screening experiment. [0135] Initially, toluene, tetrahydrofuran (THF), and isopropyl acetate (iPAc) were tested as solvents. Compound (12) was dissolved in the respective solvent and then treated with triethylamine and the respective acid chloride (methanesulfonyl chloride (MsCl) or 4- toluenesulfonyl chloride (TsCl)) at room temperature. After the first IPC, the reaction mixture was warmed to an internal temperature of 50 °C and progression was monitored by IPC.

P0043-WO-PCT/P0043-WO 37JD-350579-WO Table 8 IPC Results for Reaction of MsCl with Compound (12) in Different Solvents IPC Results for Reaction of TsCl with Compound (12) in Different Solvents [0136] Addition of MsCl was strongly exothermic, and the reactions were completed immediately at room temperature. The compound of Formula (II) (X = Cl) was observed as a by- product, and further conversion to the compound of Formula (II) (X = Cl) was observed over time. Addition of TsCl did not show a strong endotherm. Incomplete conversion was observed immediately after addition at room temperature. The compound of Formula (II) (X = OTs) could not be detected. Instead, the compound of Formula (II) (X = Cl) was observed. The Compound of Formula (II) (X = OMs) and the compound of Formula (II) (X = OTs) demonstrated poor stability, and ultimately converted to the compound of Formula (II) (X = Cl). Route B Scheme 8: Step 1 of Route B P0043-WO-PCT/P0043-WO 37JD-350579-WO [0137] Compound (9) (10 g) and triethyl amine (0.2 equiv) were dissolved in methyl acetate (10 relative volumes). At approximately 21 °C thionyl chloride (1.2 equiv) was added over 1 hr. The reaction was monitored by IPC. After 1 hr at 21 °C, IPC revealed 95.8%-a/a product purity, and 98.7%-a/a conversion (1.3%-a/a of Compound (9) remained). The reaction was quenched by the addition of water at approximately 21 °C. The pH of the organic layer was adjusted to pH 7-8 by addition of sodium hydroxide (30%-w/w). The organic layer was separated. Purity of Compound (10) in the organic layer was determined to be 97.1%-a/a by HPLC. The main impurities were the starting material (Compound (9) (1.08%-a/a) and an impurity (1.07%-a/a; 310 Da). Yield of the reaction was approximately 97% of theoretical as determined by HPLC assay of the product solution. [0138] A solution of Compound (10) in THF (10 relative volumes) was added to MeMgCl in THF (2.2 equiv) at 0 °C. After 1 hr at 0 °C, complete conversion to Compound (13) was observed by IPC (<0.05 Compound (10) remaining; 96.0 %-a/a purity; main impurity 1-(6- (chloromethyl)pyridin-2-yl)ethan-1-one (Compound (c)): 2.65%-a/a). The reaction mixture was quenched with ammonium citrate (10 relative volumes) and washed with saturated sodium bisulfite. After quenching with ammonium citrate, HPLC revealed 95.9%-a/a purity, with the Compound (c) being reduced to 2.24%-a/a in the organic layer. [0139] The reaction of Compound (10) with MeMgCl gave a clean reaction profile, with the main impurity being the respective chloromethyl ketone (2.63%-a/a) (Compound (c)). Quenching the reaction mixture with ammonium citrate worked well, with minimal losses of the product to the aqueous layer (<1% of theoretical yield). [0140] Route B features less selectivity challenges, which were reflected in higher HPLC purities. P0043-WO-PCT/P0043-WO 37JD-350579-WO Table 10 Comparison of Route A and Route B - y yl Scheme 10: Preparation incorporating Route B [0141] The conversion of Compound (10) to Compound (13) was identified as a source for impurities that proved difficult to remove in downstream steps of the synthesis of etrumadenant. For example, without wishing to be bound by theory, impurities may be formed during the conversion P0043-WO-PCT/P0043-WO 37JD-350579-WO of Compound (10) to Compound (13) (see Example 3), the downstream chemistries of which result in the formation of compound (d) and/or the formation of compound (f). Thus, a purity control point was desirable. Further, compound (16) is an oil, which makes its purification challenging. A campaign was designed to determine if a purity control point could be added at these points of the synthesis. [0142] A salt screening was initiated for Compound (13), which was prepared in a fashion similar to that described in Route B of Example 3 above, with anhydrously available methanesulfonic acid, benzenesulfonic acid, and DL-camphorsulfonic acid in the solvents methanol (MeOH), isopropyl acetate (iPAc), and methyl tert-butyl ether (MTBE). [0143] In general, Compound was in MeOH, iPAc, and MTBE, 3 relative volumes each. Methanesulfonic acid, benzenesulfonic acid, and DL-camphorsulfonic acid were then dissolved/suspended in 3 relative volumes of MeOH, iPAc, and MTBE, each. The solution of Compound (13) was added to the respective solution/suspension of the sulfonic acid and vigorously shaken. The resulting mixtures were allowed to sit at room temperature overnight. Observations are summarized below. Table 11 [0144] From this experiment, an isolable solid form of Compound (13) (Compound of Formula (IIa-ii)) was identified from treatment with methanesulfonic acid in iPAc and MTBE. MTBE and iPAc are anti-solvents for this material, while MeOH is a pro-solvent. P0043-WO-PCT/P0043-WO 37JD-350579-WO (IIa-ii) [0145] Crystallization of the identified solid form was attempted on larger scale. A solution of Compound (13), which was made in a similar fashion to that described in Route B of Example 3 above, was solvent swapped to MTBE at constant volume until Karl Fischer (KF) moisture analysis indicated a water content of ≤ 0.5%/w/w. A total of 0.9 equiv of MsOH was added in portions. Oiling out was observed during the addition of MsOH, which was reduced by adding methanol to the mixture. After complete addition, and stirring over 3 days, a crystalline solid was obtained (approx. 80% theoretical yield). [0146] Preliminary Solubility Studies for Compound of Formula (IIa-ii) [0147] Solubility investigations were performed on the resulting solid (Compound of Formula (IIa-ii)). In general, the solid material was added to a variety of solvents to determine the solubility of the material in each solvent, as well as the purity of the supernatant. The results are summarized in FIG. 1. Alcohols serve as pro-solvents, with solvent strength decreasing in the order MeOH > EtOH > n-BuOH = 2-propanol. Acetates serve as anti-solvents, with solvent strength decreasing from MeOAc > EtOAc > iPAc. THF and MEK show targeted solubility around 10 g/L at room temperature. MEK and THF are suitable as single solvent for the crystallization of Formula (IIa- ii)). iPAc is an anti-solvent, demonstrating low solubility for the product, and high solubility for impurities. The purity profile of the resulting solutions was measured by HPLC (Table 12); compounds (i), (ii), (iii), (iv), and (v) of Table 12 refer to impurities. Table 12 P0043-WO-PCT/P0043-WO 37JD-350579-WO Methyl 6 57.1 88.1 2.74 1.01 0.83 3.93 0.98 1.15 Acetate E h l 3 771 863 350 165 <005 503 159 197 [0148] Based on the solubility data, the crystallization for the compound of Formula (IIa-ii) from MEK was attempted on an 18 g scale. Crude Compound (13), which was made in a similar fashion to that described in Route B of Example 3 above, was dissolved in 4 relative volumes of MEK. At an internal temperature of 20-30 °C, 0.9 equiv of MsOH were added. Crystallization was observed after about 10% of MsOH addition. The suspension was cooled to an internal temperature of 0-10°C, and the product collected by filtration. The obtained solids were washed with MEK, then dried under vacuum resulting in the product as a crystalline solid (90% of the yield). The purity of the product was determined to be 98.8%-a/a as determined by HPLC, as shown in FIG. 2 (chromatogram) and Table 13. Table 13 [0149] As can be seen above, no impurities were present in an amount greater than approximately 1.0%-a/a. P0043-WO-PCT/P0043-WO 37JD-350579-WO [0150] Advanced Solubility for Compound of Formula (IIa-ii) [0151] Next, the effect of A) the amount of MsOH added, and B) use of iPAc as an anti-solvent in MEK on the solubility of the compound of Formula (IIa-ii) was investigated. Excess compound of Formula (IIa-ii) (1 g) was suspended in 3 mL of MEK. MsOH and iPAc were added according to the table below. The mixture was stirred, and the supernatant was sampled for HPLC purity and assay. The solubility results are summarized in FIG. 3. Table 14 Results of Solubility Studies [0152] From this experiment, it was observed that iPAc helps decrease the solubility of Compound (13) in MEK. Additional MsOH increases the solubility of Compound (13) in MEK/iPAc mixtures. The effect of increased solubility with increasing MsOH is less pronounced when iPAc is present. Example 5: Exemplary Preparation of Compound of Formula (IIa-ii) [0153] A solution of Compound (10) (42.2 g) in THF was slowly added to a solution of methyl magnesium chloride (192 g, 22%) in THF with stirring. Upon reaction completion, the reaction was quenched by the addition of the reaction mixture to aqueous acetic acid. The mixture was warmed, P0043-WO-PCT/P0043-WO 37JD-350579-WO and the layers separated. The lower aqueous layer was discarded, and the organic layer was distilled in a solvent exchange to about 335 mL methylethylketone (MEK). The MEK product solution was clarified by filtration prior to the addition of 10.9 g methane sulfonic acid. The solution is warmed to 50-60 °C and seeded with about 0.2 g Formula (IIa-ii) crystals (which may be obtained according to methods described herein, such as Examples described herein without the use of seeding with Formula (IIa-ii)). After the initiation of crystallization, 9.8 g methane sulfonic acid was added, and the mixture cooled to 0 °C. The solid product was filtered, washed with isopropyl acetate and dried to yield the intermediate Formula (IIa-ii) in approximately 90% yield, 99.5% purity as determined by HPLC, shown in FIG. 4. The resulting solid was characterized by XRPD and DVS, shown in FIG. 5 and FIG. 6, respectively. [0154] XRPD analysis was carried out on a PANalytical XPERT-PRO, scanning the samples between 2 and 40° 2θ. The material was placed on an XRD sample holder and gently flattened with a glass slide. The XRD sample holder was then placed into the diffractometer and analyzed using Cu K radiation (α1 λ = 1.54059 Å; α2 = 1.54426 Å; β = 1.39225 Å; α1:α2 ratio = 0.5) running in reflectance mode (step size 0.0167° 2θ) using 45 kV / 40 mA generator settings. [0155] For DVS analysis, a sample of Formula (IIa-ii) (591 mg) was placed in a tared sample pan in a ProUmid DVS. The instrument was programmed to maintain 25 °C throughout the experiment and to dry the sample at 0% RH for two hours, followed by stepwise increase to 90% RH. Each step raised the RH in 10% increments and was kept so for two hours. The RH was then reduced to 0% in the same fashion. Example 6: Exemplary Preparation of Compound (16) From Compound (13) Scheme 12 [0156] The conversion of Compound (13) to an azide intermediate (Compound (16)) in toluene was attempted. Approximately 0.5 g of Compound (13) was dissolved in 5 mL toluene (10 relative P0043-WO-PCT/P0043-WO 37JD-350579-WO volumes). Water (6 relative volumes) and saturated NaCl solution (6 relative volumes) were added, and the pH adjusted to 11 by addition of NaOH (30%-w/w). The aqueous layer was separated and discarded. The organic layer, sodium azide (2 eq.) in water (1.5 relative volumes) and tetrabutylammonium bromide (TBABr) (10 mol%) was added. The reaction progress was monitored by IPC. After 1 hr of mixing at an internal temperature of 40 °C, the mixture was warmed to an internal temperature of 60 °C and allowed to stir for an additional 3 hrs. The mixture was then cooled to an internal temperature of 25 °C and allowed to stir overnight, at which point IPC showed 98.3 % conversion, and 96.0% Compound (16) purity, as illustrated in FIG. 7 (chromatogram) and Table 15. Table 15 Example 7: xemp ary reparat on o Compound ( 6) rom Compound o Formula (IIa-ii)) Scheme 13 [0157] Formula (IIa-ii) was mixed with toluene and water and then aqueous sodium hydroxide. The mixture was warmed, and the layers allowed to separate. Tetrabutylammonium bromide and water were added to the organic fraction and the mixture was stirred; sodium azide was added and the mixture was stirred under reflux. Upon reaction completion, the mixture was cooled and the P0043-WO-PCT/P0043-WO 37JD-350579-WO bottom aqueous layer was discarded. The organic fraction was then washed repeatedly with aqueous sodium acetate to afford an organic solution containing Compound (16) with 99.5% purity. Preparing Compound (16) from Compound of Formula (IIa-ii) reduced amounts of observed impurities. Example 8: Process for Preparing Etrumadenant P0043-WO-PCT/P0043-WO 37JD-350579-WO [0158] Step 1 [0159] Water, potassium carbonate, and 3-bromo-2-methylbenzoic acid (Compound (1)) were mixed and added to a reactor containing n-butanol, [Pd(C3H5)Cl]2 and XPhos (IUPAC: dicyclohexyl[2′,4′,6′-tris(propan-2-yl)[1,1′-bipheny l]-2-yl]phosphane). K ₄ [Fe(CN) ₆ ]•3H ₂ O was charged to the reactor. The reaction mass was subsequently stirred with warming until IPC by HPLC indicated the reaction was complete. The slurry was cooled, filtered, and solvent swap distilled with addition of water. To the aqueous product solution was charged FeCl ₃ and the solution was stirred at 15°C for 0.5-1 h until residual cyanide was found to be ≤ 5 ppm and then filtered. Me-THF was charged to the aqueous product solution, and the mixture was acidified. The phases were separated, and the organic product solution washed with sodium sulfate. The organic product solution was solvent swap distilled with addition of IPA. The solution was warmed, and water was charged. The mixture was cooled and filtered. The product wet cake was washed with IPA/water and dried to afford Compound (3). [0160] Step 2 [0161] 3-cyano-2-methylbenzoic acid (Compound (3)), toluene, thionyl chloride and dimethylformamide (DMF) were combined, and the mixture was stirred with warming until IPC by HPLC indicated the reaction was complete. The mixture was solvent swap distilled with addition of acetonitrile to form the acid chloride solution. To a separate reactor was added acetonitrile, potassium ethyl malonate, triethylamine (TEA), and anhydrous magnesium chloride with cooling. The acid chloride was added to the above cooled mixture, and the contents mixed with cooling until IPC by HPLC indicated the reaction was complete. HCl solution and MTBE were added, mixed, and separated. The organic layer was washed with aqueous sodium bicarbonate, solvent swap distilled with addition of THF to afford a solution of Compound (4). [0162] Step 3 [0163] A mixture of 2,2,2-trifluoroethanol, Compound (4), and guanidinium carbonate was stirred with heating until IPC by HPLC indicated the reaction was complete. The mixture was concentrated with addition of water and then basified until product dissolved. The aqueous solution was extracted with isopropyl acetate (IPAc) and the aqueous layer was acidified with citric acid to P0043-WO-PCT/P0043-WO 37JD-350579-WO crystallize product. The product was isolated by filtration, washed with water, re-slurried with acetonitrile, and dried to afford Compound (5). [0164] Step 4 [0165] Compound (5), phosphorous oxychloride (POCl ₃ ), and benzyl trimethyl ammonium chloride in acetonitrile (MeCN) are mixed to react until passing IPC, after which, the reaction mixture is quenched with water and the pH adjusted with 25% ammonium hydroxide. The mixture is filtered and the wetcake is re-slurried with water. The wet cake is dissolved with tetrahydrofuran and treated with activated carbon. The resulting solution is concentrated, and isopropyl alcohol is added to crystallize the product (Compound (6)). The filter cake is rinsed with isopropyl alcohol after centrifugation, and then vacuum dried until IPC results pass to obtain Compound (6). [0166] Step 5 [0167] A 2-propanol solution of Compound (6), copper iodide, 1,1′-(bisdiphenylphosphino)- ferrocene (dppf), diisopropylamine (DIPA), and TIPS-acetylene was allowed to stir with warming. Palladium (II) acetate (Pd(OAc) ₂ ) was added, and the reaction mixture was heated until reaction completion. The resultant mixture was seeded with Compound (7) crystals, which were made according to methods known in the art, and combined with Na2EDTA and N-acetyl-L-cysteine. Water was added and the solid product (Compound (7)) was allowed to crystallize with gradual cooling. Compound (7) was filtered, washed with 2-propanol followed by water, and dried. [0168] Step 6 [0169] An aqueous solution of tetrabutylammonium hydroxide (TBAH) and phosphoric acid was added to a solution of Compound (7) in THF. Partial neutralization of TBAH was achieved with H3PO4 to generate buffer (buffer strength range of about 40-80%, or about 55-65%). The mixture was allowed to stir with warming (to a temperature between about 25-35 °C, or about 27- 33 °C). Upon reaction completion, the reaction mixture was quenched with dilute acetic acid. IPA was added and the solution was solvent swapped to IPA. The resultant mixture was cooled, and the solid product (Compound (8)) was collected by filtration. Compound (8) was then washed with IPA, isolated and dried. P0043-WO-PCT/P0043-WO 37JD-350579-WO [0170] Step 7 [0171] Thionyl chloride was added to a solution of Compound (9) and triethylamine in methyl acetate. Upon reaction completion, aqueous sodium hydroxide was added, and the layers were allowed to separate, and the lower aqueous layer was discarded. The organic fraction was washed with sodium chloride solution, heated to reflux and a solvent exchange to THF by distillation was conducted to yield the product, Compound (10) as a solution in THF. [0172] Step 8 [0173] A solution of Compound (10) in THF was combined with a solution of methyl magnesium chloride in THF with stirring. Upon reaction completion, the reaction was quenched by the addition of the reaction mixture to aqueous acetic acid. The mixture was warmed, and the layers allowed to separate. The lower aqueous layer was discarded, and the organic layer was distilled in a solvent exchange to methylethylketone (MEK). The MEK product solution was clarified prior to the addition of methane sulfonic acid. The solution was warmed and seeded with the compound of Formula (IIa-ii), which was made according to methods described herein. After the initiation of crystallization, more methane sulfonic acid was added and the mixture was cooled. The solid product was filtered, washed with isopropyl acetate and dried to yield the Formula (IIa-ii). [0174] Step 9 [0175] The compound of Formula (IIa-ii) was mixed with toluene and water and then aqueous sodium hydroxide. The mixture was warmed, and the layers allowed to separate. Tetrabutylammonium bromide and water were added to the organic fraction and the mixture was stirred; sodium azide was added and the mixture was stirred under reflux. Upon reaction completion, the mixture was cooled, and the bottom aqueous layer was discarded. The organic fraction was then washed repeatedly with aqueous sodium acetate. The organic solution containing Compound (16) was then directly taken forward to Step 10. [0176] Step 10 [0177] The Compound (16) solution was added to a mixture of Compound (8) and THF; tetrakis(acetonitrile)copper(I)triflate in acetonitrile solution was added to the Compound (16) P0043-WO-PCT/P0043-WO 37JD-350579-WO mixture and the reaction mixture was stirred under reflux. Upon reaction completion, the mixture was cooled and washed with ammonium acetate/EDTA solution followed by an ammonium acetate solution. The resultant organic fraction was combined with toluene, seeded with etrumadenant seed crystals, which can be made according to methods known in the art (see, e.g., WO 2020/018680), heated to reflux and a solvent switch to toluene by distillation was conducted. The solution was allowed to cool, and the desired product was isolated by filtration, washed with IPA, water, and then dried to yield etrumadenant (crude). [0178] Step 11 [0179] Etrumadenant (crude) was dissolved in a warm solution of acetone and water. The solution was treated with activated carbon then concentrated by distillation and seed crystals of etrumadenant, which can be made according to methods known in the art (see, e.g., WO 2020/018680), were added to the warm solution. The desired product was allowed to crystallize at which point purified water was added and the slurry was cooled. The solid product was isolated by filtration, washed with a solution of acetone/water, and dried to yield purified etrumadenant. [0180] A representative HPLC chromatogram of etrumadenant as isolated is shown in FIG. 8. [0181] Although the foregoing disclosure has been described in some detail by way of illustration and Example for purposes of clarity of understanding, one of skill in the art will appreciate that certain changes and modifications may be practiced within the scope of the appended claims. In addition, each reference provided herein is incorporated by reference in its entirety to the same extent as if each reference was individually incorporated by reference. Where a conflict exists between the instant application and a reference provided herein, the instant application shall dominate.