Methods of Synthesizing EGFR Inhibitors CROSS REFERENCE TO RELATED APPLICATIONS This application claims the benefit of United States Provisional Application Nos. 63/323,249, filed on March 24, 2022, 63/422,645, filed on November 4, 2022 and 63/435,108, filed on December 23, 2022, which are incorporated herein by reference in their entirety. TECHNICAL FIELD This disclosure features methods for preparing tetrahydro-4H-pyrrolo[3,2- c]pyridin-4-one-containing chemical entities (e.g., a compound or a pharmaceutically acceptable salt thereof) that inhibit epidermal growth factor receptor (EGFR, ERBB1) and/or Human epidermal growth factor receptor 2 (HER2, ERBB2) as well as synthetic intermediates useful for the preparation of said chemical entities. The methods include, for example, improved methods for synthesizing compounds of formula (I) as described herein. BACKGROUND Epidermal growth factor receptor (EGFR, ERBB1) and Human epidermal growth factor receptor 2 (HER2, ERBB2) are members of a family of proteins which regulate cellular processes implicated in tumor growth, including proliferation and differentiation. Several investigators have demonstrated the role of EGFR and HER2 in development and cancer (Reviewed in Salomon, et al., Crit. Rev. Oncol. Hematol. (1995) 19:183-232, Klapper, et al., Adv. Cancer Res. (2000) 77, 25-79 and Hynes and Stern, Biochim. Biophys. Acta (1994) 1198:165-184). EGFR overexpression is present in at least 70% of human cancers, such as non-small cell lung carcinoma (NSCLC), breast cancer, glioma, and prostate cancer. HER2 overexpression occurs in approximately 30% of all breast cancer. It has also been implicated in other human cancers including colon, ovary, bladder, stomach, esophagus, lung, uterus and prostate. HER2 overexpression has also been correlated with poor prognosis in human cancer, including metastasis, and early relapse. Tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one-containing chemical entities that inhibit epidermal growth factor receptor and/or Human epidermal growth factor receptor 2 are described in, e.g., PCT/US2021/051504, filed on September 22, 2021; PCT/US2021/054191, filed on October 8, 2021; and PCT/US2021/057348, filed on October 8, 2021, each of which is incorporated by reference in its entirety. SUMMARY This disclosure features methods for preparing tetrahydro-4H-pyrrolo[3,2- c]pyridin-4-one-containing chemical entities (e.g., a compound or a pharmaceutically acceptable salt thereof) that inhibit epidermal growth factor receptor (EGFR, ERBB1) and/or Human epidermal growth factor receptor 2 (HER2, ERBB2) as well as synthetic intermediates useful for the preparation of said chemical entities. The methods include, for example, improved methods for synthesizing compounds of formula (I) as described herein. In one aspect, this disclosure features methods of preparing a compound of Formula (I), or a pharmaceutically acceptable salt thereof, which include contacting a compound of formula (II) with a compound of formula (III), Formula (III), in which Y, Z, R ^1c , R ^2a , R ^2b , R ^3a , R ^3b ,R ⁴ , ring A and ring C can be as defined anywhere herein. In one aspect, this disclosure features compound of Formula (I), or a pharmaceutically acceptable salt thereof, , in which R ^1c , R ^2a , R ^2b , R ^3a , R ^3b , R ⁴ , ring A and ring C can be as defined anywhere herein. In another aspect, this disclosure features compound of Formula (I), or a pharmaceutically acceptable salt thereof, which is prepared by a process as described anywhere herein, and in which R ^1c , R ^2a , R ^2b , R ^3a , R ^3b ,R ⁴ , ring A and ring C can be as defined anywhere herein. Procedures used heretofore to prepare the compounds described herein utilized oxidizing agents (e.g., peroxy acids, e.g., m-CPBA) in certain bond forming (e.g., cyclization) steps. Additionally, the oxidizing agents (e.g., peroxy acids, e.g., m-CPBA) were employed in at least stoichiometric amounts, and typically in excess. Advantageously, the inventors have surprisingly found that these bond forming (e.g., cyclization) steps can be carried out in the absence of oxidizing agents (e.g., peroxy acids, e.g., m-CPBA), thereby rendering the desired transformation more amenable to safer and more cost effective scale-up. The disclosure may be more fully appreciated by reference to the following description, including the following glossary of terms and the concluding examples. It is to be appreciated that certain features of the disclosed compositions and methods which are, for clarity, described herein in the context of separate aspects, may also be provided in combination in a single aspect. Conversely, various features of the disclosed compositions and methods that are, for brevity, described in the context of a single aspect, may also be provided separately or in any sub-combination. The term "halo" refers to fluoro (F), chloro (Cl), bromo (Br), or iodo (I). The term “oxo” refers to a divalent doubly bonded oxygen atom (i.e., “=O”). As used herein, oxo groups are attached to carbon atoms to form carbonyls. The term "alkyl" refers to a saturated acyclic hydrocarbon radical that may be a straight chain or branched chain, containing the indicated number of carbon atoms. For example, C1-10 indicates that the group may have from 1 to 10 (inclusive) carbon atoms in it. Alkyl groups can either be unsubstituted or substituted with one or more substituents. Non-limiting examples include methyl, ethyl, iso-propyl, tert-butyl, n-hexyl. The term “saturated” as used in this context means only single bonds present between constituent carbon atoms and other available valences occupied by hydrogen and/or other substituents as defined herein. The term "alkoxy" refers to an -O-alkyl radical (e.g., -OCH3). The term "alkylene" refers to a divalent alkyl (e.g., -CH2-). The term "alkenyl" refers to an acyclic hydrocarbon chain that may be a straight chain or branched chain having one or more carbon-carbon double bonds. The alkenyl moiety contains the indicated number of carbon atoms. For example, C2-6 indicates that the group may have from 2 to 6 (inclusive) carbon atoms in it. Alkenyl groups can either be unsubstituted or substituted with one or more substituents. The term "alkynyl" refers to an acyclic hydrocarbon chain that may be a straight chain or branched chain having one or more carbon-carbon triple bonds. The alkynyl moiety contains the indicated number of carbon atoms. For example, C2-6 indicates that the group may have from 2 to 6 (inclusive) carbon atoms in it. Alkynyl groups can either be unsubstituted or substituted with one or more substituents. The term "aryl" refers to a 6-20 carbon mono-, bi-, tri- or polycyclic group wherein at least one ring in the system is aromatic (e.g., 6-carbon monocyclic, 10-carbon bicyclic, or 14-carbon tricyclic aromatic ring system); and wherein 0, 1, 2, 3, or 4 atoms of each ring may be substituted by a substituent. Examples of aryl groups include phenyl, naphthyl, tetrahydronaphthyl, and the like. The term "cycloalkyl" as used herein refers to cyclic saturated hydrocarbon groups having, e.g., 3 to 20 ring carbons, preferably 3 to 16 ring carbons, and more preferably 3 to 12 ring carbons or 3-10 ring carbons or 3-6 ring carbons, wherein the cycloalkyl group may be optionally substituted. Examples of cycloalkyl groups include, without limitation, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Cycloalkyl may include multiple fused and/or bridged rings. Non-limiting examples of fused/bridged cycloalkyl includes: bicyclo[1.1.0]butane, bicyclo[2.1.0]pentane, bicyclo[1.1.1]pentane, bicyclo[3.1.0]hexane, bicyclo[2.1.1]hexane, bicyclo[3.2.0]heptane, bicyclo[4.1.0]heptane, bicyclo[2.2.1]heptane, bicyclo[3.1.1]heptane, bicyclo[4.2.0]octane, bicyclo[3.2.1]octane, bicyclo[2.2.2]octane, and the like. Cycloalkyl also includes spirocyclic rings (e.g., spirocyclic bicycle wherein two rings are connected through just one atom). Non-limiting examples of spirocyclic cycloalkyls include spiro[2.2]pentane, spiro[2.5]octane, spiro[3.5]nonane, spiro[3.5]nonane, spiro[3.5]nonane, spiro[4.4]nonane, spiro[2.6]nonane, spiro[4.5]decane, spiro[3.6]decane, spiro[5.5]undecane, and the like. The term “saturated” as used in this context means only single bonds present between constituent carbon atoms. The term "cycloalkenyl" as used herein means partially unsaturated cyclic hydrocarbon groups having 3 to 20 ring carbons, preferably 3 to 16 ring carbons, and more preferably 3 to 12 ring carbons or 3-10 ring carbons or 3-6 ring carbons, wherein the cycloalkenyl group may be optionally substituted. Examples of cycloalkenyl groups include, without limitation, cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl. As partially unsaturated cyclic hydrocarbon groups, cycloalkenyl groups may have any degree of unsaturation provided that one or more double bonds is present in the ring, none of the rings in the ring system are aromatic, and the cycloalkenyl group is not fully saturated overall. Cycloalkenyl may include multiple fused and/or bridged and/or spirocyclic rings. The term “heteroaryl”, as used herein, means a mono-, bi-, tri- or polycyclic group having 5 to 20 ring atoms, alternatively 5, 6, 9, 10, or 14 ring atoms; wherein at least one ring in the system contains one or more heteroatoms independently selected from the group consisting of N, O, and S and at least one ring in the system is aromatic (but does not have to be a ring which contains a heteroatom, e.g. tetrahydroisoquinolinyl, e.g., tetrahydroquinolinyl). Heteroaryl groups can either be unsubstituted or substituted with one or more substituents. Examples of heteroaryl include thienyl, pyridinyl, furyl, oxazolyl, oxadiazolyl, pyrrolyl, imidazolyl, triazolyl, thiodiazolyl, pyrazolyl, isoxazolyl, thiadiazolyl, pyranyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, thiazolyl benzothienyl, benzoxadiazolyl, benzofuranyl, benzimidazolyl, benzotriazolyl, cinnolinyl, indazolyl, indolyl, isoquinolinyl, isothiazolyl, naphthyridinyl, purinyl, thienopyridinyl, pyrido[2,3- d]pyrimidinyl, pyrrolo[2,3-b]pyridinyl, quinazolinyl, quinolinyl, thieno[2,3-c]pyridinyl, pyrazolo[3,4-b]pyridinyl, pyrazolo[3,4-c]pyridinyl, pyrazolo[4,3-c]pyridine, pyrazolo[4,3-b]pyridinyl, tetrazolyl, chromane, 2,3-dihydrobenzo[b][1,4]dioxine, benzo[d][1,3]dioxole, 2,3-dihydrobenzofuran, tetrahydroquinoline, 2,3- dihydrobenzo[b][1,4]oxathiine, isoindoline, and others. In some embodiments, the heteroaryl is selected from thienyl, pyridinyl, furyl, pyrazolyl, imidazolyl, isoindolinyl, pyranyl, pyrazinyl, and pyrimidinyl. For purposes of clarification, heteroaryl also includes aromatic lactams, aromatic cyclic ureas, or vinylogous analogs thereof, in which each ring nitrogen adjacent to a carbonyl is tertiary (i.e., all three valences are occupied by non- hydrogen substituents), such as one or more of pyridone (e.g., , , or ), pyrimidone (e.g., or ), pyridazinone (e.g., or ), pyrazinone (e.g., or ), and imidazolone (e.g., ), wherein each ring nitrogen adjacent to a carbonyl is tertiary (i.e., the oxo group (i.e., “=O”) herein is a constituent part of the heteroaryl ring). The term "heterocyclyl" refers to a mono-, bi-, tri-, or polycyclic saturated ring system with 3-16 ring atoms (e.g., 5-8 membered monocyclic, 8-12 membered bicyclic, or 11-14 membered tricyclic ring system) having 1-3 heteroatoms if monocyclic, 1-6 heteroatoms if bicyclic, or 1-9 heteroatoms if tricyclic or polycyclic, said heteroatoms selected from O, N, or S (e.g., carbon atoms and 1-3, 1-6, or 1-9 heteroatoms of N, O, or S if monocyclic, bicyclic, or tricyclic, respectively), wherein 0, 1, 2 or 3 atoms of each ring may be substituted by a substituent. Examples of heterocyclyl groups include piperazinyl, pyrrolidinyl, dioxanyl, morpholinyl, tetrahydrofuranyl, and the like. Heterocyclyl may include multiple fused and bridged rings. Non-limiting examples of fused/bridged heteorocyclyl includes: 2-azabicyclo[1.1.0]butane, 2-azabicyclo[2.1.0]pentane, 2- azabicyclo[1.1.1]pentane, 3-azabicyclo[3.1.0]hexane, 5-azabicyclo[2.1.1]hexane, 3- azabicyclo[3.2.0]heptane, octahydrocyclopenta[c]pyrrole, 3-azabicyclo[4.1.0]heptane, 7- azabicyclo[2.2.1]heptane, 6-azabicyclo[3.1.1]heptane, 7-azabicyclo[4.2.0]octane, 2- azabicyclo[2.2.2]octane, 3-azabicyclo[3.2.1]octane, 2-oxabicyclo[1.1.0]butane, 2- oxabicyclo[2.1.0]pentane, 2-oxabicyclo[1.1.1]pentane, 3-oxabicyclo[3.1.0]hexane, 5- oxabicyclo[2.1.1]hexane, 3-oxabicyclo[3.2.0]heptane, 3-oxabicyclo[4.1.0]heptane, 7- oxabicyclo[2.2.1]heptane, 6-oxabicyclo[3.1.1]heptane, 7-oxabicyclo[4.2.0]octane, 2- oxabicyclo[2.2.2]octane, 3-oxabicyclo[3.2.1]octane, and the like. Heterocyclyl also includes spirocyclic rings (e.g., spirocyclic bicycle wherein two rings are connected through just one atom). Non-limiting examples of spirocyclic heterocyclyls include 2- azaspiro[2.2]pentane, 4-azaspiro[2.5]octane, 1-azaspiro[3.5]nonane, 2- azaspiro[3.5]nonane, 7-azaspiro[3.5]nonane, 2-azaspiro[4.4]nonane, 6- azaspiro[2.6]nonane, 1,7-diazaspiro[4.5]decane, 7-azaspiro[4.5]decane 2,5- diazaspiro[3.6]decane, 3-azaspiro[5.5]undecane, 2-oxaspiro[2.2]pentane, 4- oxaspiro[2.5]octane, 1-oxaspiro[3.5]nonane, 2-oxaspiro[3.5]nonane, 7- oxaspiro[3.5]nonane, 2-oxaspiro[4.4]nonane, 6-oxaspiro[2.6]nonane, 1,7- dioxaspiro[4.5]decane, 2,5-dioxaspiro[3.6]decane, 1-oxaspiro[5.5]undecane, 3- oxaspiro[5.5]undecane, 3-oxa-9-azaspiro[5.5]undecane and the like. The term “saturated” as used in this context means only single bonds present between constituent ring atoms and other available valences occupied by hydrogen and/or other substituents as defined herein. The term "heterocycloalkenyl" as used herein means partially unsaturated cyclic ring system with 3-16 ring atoms (e.g., 5-8 membered monocyclic, 8-12 membered bicyclic, or 11-14 membered tricyclic ring system) having 1-3 heteroatoms if monocyclic, 1-6 heteroatoms if bicyclic, or 1-9 heteroatoms if tricyclic or polycyclic, said heteroatoms selected from O, N, or S (e.g., carbon atoms and 1-3, 1-6, or 1-9 heteroatoms of N, O, or S if monocyclic, bicyclic, or tricyclic, respectively), wherein 0, 1, 2 or 3 atoms of each ring may be substituted by a substituent. Examples of heterocycloalkenyl groups include, without limitation, tetrahydropyridyl, dihydropyrazinyl, dihydropyridyl, dihydropyrrolyl, dihydrofuranyl, dihydrothiophenyl. As partially unsaturated cyclic groups, heterocycloalkenyl groups may have any degree of unsaturation provided that one or more double bonds is present in the ring, none of the rings in the ring system are aromatic, and the heterocycloalkenyl group is not fully saturated overall. Heterocycloalkenyl may include multiple fused and/or bridged and/or spirocyclic rings. As used herein, examples of aromatic rings include: benzene, pyridine, pyrimidine, pyrazine, pyridazine, pyridone, pyrrole, pyrazole, oxazole, thioazole, isoxazole, isothiazole, and the like. As used herein, when a ring is described as being “partially unsaturated”, it means said ring has one or more additional degrees of unsaturation (in addition to the degree of unsaturation attributed to the ring itself; e.g., one or more double or tirple bonds between constituent ring atoms), provided that the ring is not aromatic. Examples of such rings include: cyclopentene, cyclohexene, cycloheptene, dihydropyridine, tetrahydropyridine, dihydropyrrole, dihydrofuran, dihydrothiophene, and the like. For the avoidance of doubt, and unless otherwise specified, for rings and cyclic groups (e.g., aryl, heteroaryl, heterocyclyl, heterocycloalkenyl, cycloalkenyl, cycloalkyl, and the like described herein) containing a sufficient number of ring atoms to form bicyclic or higher order ring systems (e.g., tricyclic, polycyclic ring systems), it is understood that such rings and cyclic groups encompass those having fused rings, including those in which the points of fusion are located (i) on adjacent ring atoms (e.g., [x.x.0] ring systems, in g y g g y of ring atoms (bridged ring systems having all bridge lengths > 0) (e.g., , , The term “pharmaceutically acceptable salt” refers to a formulation of a compound that does not cause significant irritation to an organism to which it is administered and does not abrogate the biological activity and properties of the compound. In certain instances, pharmaceutically acceptable salts are obtained by reacting a compound described herein, with acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid and the like. In some instances, pharmaceutically acceptable salts are obtained by reacting a compound having acidic group described herein with a base to form a salt such as an ammonium salt, an alkali metal salt, such as a sodium or a potassium salt, an alkaline earth metal salt, such as a calcium or a magnesium salt, a salt of organic bases such as dicyclohexylamine, N-methyl-D-glucamine, tris(hydroxymethyl)methylamine, and salts with amino acids such as arginine, lysine, and the like, or by other methods previously determined. The pharmacologically acceptable salt s not specifically limited as far as it can be used in medicaments. Examples of a salt that the compounds described hereinform with a base include the following: salts thereof with inorganic bases such as sodium, potassium, magnesium, calcium, and aluminum; salts thereof with organic bases such as methylamine, ethylamine and ethanolamine; salts thereof with basic amino acids such as lysine and ornithine; and ammonium salt. The salts may be acid addition salts, which are specifically exemplified by acid addition salts with the following: mineral acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, and phosphoric acid:organic acids such as formic acid, acetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid, methanesulfonic acid, and ethanesulfonic acid; acidic amino acids such as aspartic acid and glutamic acid. According to the disclosure, the compounds prepared by the methods described herein can be obtained as a single stereoisomer or a mixture of stereoisomers. Compounds prepared by the methods described herein may also contain unnatural proportions of one, two, three, or more atomic isotopes at one or more of the atoms that constitute such compounds. Unnatural proportions of an isotope may be defined as ranging from the amount found in nature to an amount consisting of 100% of the atom in question. For example, the compounds may incorporate radioactive isotopes, such as, for example, tritium ( ³ H), iodine-125 ( ¹²⁵ I), fluorine-18 ( ¹⁸ F), and/or carbon-14 (14C), or non- radioactive isotopes, such as deuterium ( ² H), carbon-13 ( ¹³ C), and/or nitrogen-15 ( ¹⁵ N). Such isotopic variations can provide additional utilities to those described elsewhere within this application. For instance, isotopic variants of the compounds of the invention may find additional utility, including but not limited to, as diagnostic and/or imaging reagents, or as cytotoxic/radiotoxic therapeutic agents. Additionally, isotopic variants of the compounds of the invention can have altered pharmacokinetic and pharmacodynamic characteristics which can contribute to enhanced safety, tolerability or efficacy during treatment. All isotopic variations of the compounds of the present invention, whether radioactive or not, are intended to be encompassed within the scope of the present invention. The details of one or more embodiments of the subject matter claimed are set forth in the accompanying drawings and the description below. Other features, and advantages of the invention will be apparent from the description and drawings, and from the claims. DESCRIPTION OF DRAWINGS FIGS.1A-1C show the ¹ HNMR and LCMS spectra of control experiments investigating compatibility of 5a and 6a with NH4OAc. FIG.2 shows the ¹ H NMR spectrum of compound 101. FIG.3 shows the ¹ H NMR spectrum of compound 102. FIG.4A. shows the LC-MS spectrum of compound 102. FIG.4B shows the powder of compound 102 FIGS 5A-5CC show the ¹ H NMR, ¹³ C NMR, 19F NMR, and NOESY NMR of the compounds synthesized in examples 7-45. DETAILED DESCRIPTION This disclosure features methods for preparing tetrahydro-4H-pyrrolo[3,2- c]pyridin-4-one-containing chemical entities (e.g., a compound or a pharmaceutically acceptable salt thereof) that inhibit epidermal growth factor receptor (EGFR, ERBB1) and/or Human epidermal growth factor receptor 2 (HER2, ERBB2) as well as synthetic intermediates useful for the preparation of said chemical entities. The methods include, for example, improved methods for synthesizing compounds of formula (I) as described herein. Preparation of Compounds of Formula (I) In one aspect, this disclosure features methods of preparing a compound of Formula (I), or a pharmaceutically acceptable salt thereof, which include contacting a compound of formula (II) with a compound of formula (III), in which Y, Z, R ^1c , R ^2a , R ^2b , R ^3a , R ^3b ,R ⁴ , ring A and ring C can be as defined anywhere herein. By way of example: Y is selected from –OH or –NH2; Z is selected from • –C(=O)H; or • –CH(R)2 wherein each R independently selected from halo, alkoxy, OH or SO3M (M = Li, Na, K or NH4 ⁺ ), provided that when one R is OH, the other R cannot be halo, alkoxy or OH; R ^1c is selected from H, and R ^d ; each of R ^2a , R ^2b , R ^3a , and R ^3b is independently selected from the group consisting of: H; halo; -OH; -C(O)OH or –C(O)NH2; -CN; -R ^b ; -L ^b -R ^b ; -C1-6 alkoxy or -C1-6 thioalkoxy, each optionally substituted with from 1-6 R ^a ; -NR ^e R ^f ; -R ^g ; and -(L ^g )g-R ^g ; two of variables R ^2a , R ^2b , R ^3a , and R ^3b , together with the Ring B ring atoms to which each is attached, form a fused saturated or unsaturated ring of 3-12 ring atoms; • wherein from 0-2 of the ring atoms are each an independently selected heteroatom (in addition to –N(R ^1c )- when –N(R ^1c )- forms part of the fused saturated or unsaturated ring), wherein each of the independently selected heteroatoms is selected from the group consisting of N, NH, N(R ^d ), O, and S(O)0-2; and • wherein the fused saturated or unsaturated ring of 3-12 ring atoms is optionally substituted with from 1-4 substituents independently selected from the group consisting of oxo, R ^c , and R ^W ; Ring A is R ^g ; R ⁴ is selected from the group consisting of: H and R ^d ; Ring C is selected from the group consisting of: • • wherein: o each X ^b is independently X, R ^c , or H; and o each X ^a is independently selected from the group consisting of: H, halo; cyano; C1-10 alkyl which is optionally substituted with from 1-6 independently selected R ^a ; C2-6 alkenyl; -S(O)1-2(C1-4 alkyl); -S(O)(=NH)(C1-4 alkyl); -NR ^e R ^f ; –OH; - S(O)1-2NR’R’’; -C1-4 thioalkoxy; -NO2; -C(=O)(C1-10 alkyl); -C(=O)O(C1-4 alkyl); -C(=O)OH; -C(=O)NR’R’’; and –SF5; • 2-pyridyl or 3-pyridyl, each optionally substituted with X and further optionally substituted with from 1-4 R ^c ; • 2-pyridonyl or 4-pyridonyl, each optionally substituted with X and further optionally substituted with from 1-4 R ^c , wherein the ring nitrogen atom is optionally substituted with R ^d ; • heteroaryl including 6 ring atoms, wherein from 2-4 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), and N(R ^d ), and wherein the heteroaryl is optionally substituted with X and further optionally substituted with from 1-4 R ^c ; • heteroaryl including 5 ring atoms, wherein from 1-4 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R ^d ), O, and S(O) ^0-2 , and wherein the heteroaryl is optionally substituted with X and further optionally substituted with from 1-4 R ^c ; • bicyclic heteroaryl including 7-10 ring atoms, wherein from 1-4 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R ^d ), O, and S(O)0-2, and wherein the heteroaryl is substituted with X and optionally substituted with from 1-4 substituents independently selected from the group consisting of oxo and R ⁷ ; • bicyclic C5-10 cycloalkyl or C5-10 cycloalkenyl, each of which is substituted with X and is optionally substituted with from 1-4 substituents independently selected from the group consisting of oxo and R ⁷ ; • heterocyclyl or heterocycloalkenyl including from 5-10 ring atoms, wherein from 1-3 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R ^d ), O, and S(O)0-2, and wherein the heterocyclyl or heterocycloalkenyl is substituted with X and optionally substituted with from 1-4 substituents independently selected from the group consisting of oxo and R ⁷ ; and • C10 or C14 aryl substituted with X and optionally substituted with from 1-4 R ⁷ ; X is X*, wherein X* is selected from halo, triflate, tosylate, or mesylate; or X is X ¹ ; each R ⁷ is an independently selected R ^c ; n is 0, 1, 2, or 3; X ¹ is selected from the group consisting of: (a) –O-L ¹ -R ⁵ ; and (b) ; L ¹ and L ² are independently selected from the group consisting of: a bond and C1-10 alkylene optionally substituted with from 1-6 R ^a ; R ⁵ is selected from the group consisting of: • heteroaryl including from 5-10 ring atoms, wherein from 1-4 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R ^d ), O, and S(O)0-2, and wherein the heteroaryl is optionally substituted with from 1-4 R ^c ; • C6-10 aryl optionally substituted with from 1-4 R ^c ; • C3-10 cycloalkyl or C3-10 cycloalkenyl, each optionally substituted with from 1-4 substituents each independently selected from the group consisting of: oxo and R ^c ; • wherein Ring D is heterocyclylene or heterocycloalkenylene including from 3-10 ring atoms, wherein from 0-2 ring atoms (in addition to the ring nitrogen atom bonded to R ^X ) are heteroatoms, each independently selected from the group consisting of N, N(H), N(R ^d ), O, and S(O)0-2, and wherein the heterocyclylene or heterocycloalkenylene is optionally substituted with from 1-4 substituents each independently selected from the group consisting of: oxo and –R ^c ; • -S(O)0-2(C1-6 alkyl) which is optionally substituted with from 1-6 R ^a ; • -R ^W • -R ^g2 -R ^W or -R ^g2 -R ^Y ; • -L ⁵ -R ^g ; and • -L ⁵ -R ^g2 -R ^W or –L ⁵ -R ^g2 -R ^Y ; provided that when L ¹ is a bond, then R ⁵ is other than -S(O)0-2(C1-6 alkyl) which is optionally substituted with from 1-6 R ^a ; -L ⁵ -R ^g ; -L ⁵ -R ^g2 -R ^W ; or –L ⁵ -R ^g2 -R ^Y ; R ⁶ is selected from the group consisting of: • H; • halo; • -OH; • -NR ^e R ^f ; • -R ^g ; • -R ^w • -L ⁶ -R ^g ; • -R ^g2 -R ^W or -R ^g2 -R ^Y ; • -L ⁶ -R ^g2 -R ^W or -L ⁶ -R ^g2 -R ^Y ; and • -C1-6 alkoxy or -S(O)0-2(C1-6 alkyl), each optionally substituted with from 1-6 R ^a ; L ⁵ and L ⁶ are independently –O-, -S(O)0-2, -NH, or -N(R ^d )-; and R ^W is –L ^W -W, wherein L ^W is C(=O), S(O)1-2, OC(=O)*, NHC(=O)*, NR ^d C(=O)*, NHS(O)1-2*, or NR ^d S(O)1-2*, wherein the asterisk represents point of attachment to W, and W is C2-6 alkenyl; C2-6 alkynyl; or C3-10 allenyl, each of which is optionally substituted with from 1-3 R ^a and further optionally substituted with R ^g , wherein W is attached to L ^W via an sp ² or sp hybridized carbon atom, thereby providing an α, β-unsaturated system; and R ^X is C(=O)(C1-6 alkyl) or S(O)2(C1-6 alkyl), each of which is optionally substituted with from 1-6 R ^a ; and R ^Y is selected from the group consisting of: -R ^g and -(L ^g )g-R ^g . each occurrence of R ^a is independently selected from the group consisting of: –OH; - halo; –NR ^e R ^f ; C1-4 alkoxy; C1-4 haloalkoxy; -C(=O)O(C1-4 alkyl); -C(=O)(C1-4 alkyl); - C(=O)OH; -CONR’R’’; -S(O)1-2NR’R’’; -S(O)1-2(C1-4 alkyl); and cyano; each occurrence of R ^b is independently C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl, each of which is optionally substituted with from 1-6 R ^a ; each occurrence of L ^b is independently C(=O); C(=O)O; S(O)1-2; C(=O)NH*; C(=O)NR ^d *; S(O) ^1-2 NH*; or S(O) ^1-2 N(R ^d )*, wherein the asterisk represents point of attachment to R ^b ; each occurrence of R ^c is independently selected from the group consisting of: halo; cyano; C1-10 alkyl which is optionally substituted with from 1-6 independently selected R ^a ; C3-5 cycloalkyl; C2-6 alkenyl; C2-6 alkynyl; C1-4 alkoxy optionally substituted with C1-4 alkoxy or C1-4 haloalkoxy; C1-4 haloalkoxy; -S(O)1-2(C1-4 alkyl); -S(O)(=NH)(C1-4 alkyl); -NR ^e R ^f ; –OH; -S(O)1-2NR’R’’; -C1-4 thioalkoxy; -NO2; -C(=O)(C1-10 alkyl); -C(=O)O(C1- 4 alkyl); -C(=O)OH; -C(=O)NR’R’’; and –SF5; each occurrence of R ^d is independently selected from the group consisting of: C1-6 alkyl optionally substituted with from 1-3 independently selected R ^a or R ^g ; -C(O)(C1-4 alkyl); - C(O)O(C1-4 alkyl); -CONR’R’’; -S(O)1-2NR’R’’; - S(O)1-2(C1-4 alkyl); -OH; and C1-4 alkoxy; each occurrence of R ^e and R ^f is independently selected from the group consisting of: H; C3-5 cycloalkyl optionally substituted with from 1-3 C1-3 alkyl group; heterocyclyl including from 3-6 ring atoms, wherein from 1-3 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R ^d ), O, and S(O)0-2 optionally substituted with from 1-4 substituents independently selected from the group consisting of oxo and R ^c ; C1-6 alkyl optionally substituted with from 1-3 substituents each independently selected from the group consisting of NR’R’’, -OH, C1-6 alkoxy, C1-6 haloalkoxy, and halo; -C(O)(C1-4 alkyl); -C(O)O(C1-4 alkyl); -CONR’R’’; -S(O)1- 2NR’R’’; - S(O)1-2(C1-4 alkyl); -OH; and C1-4 alkoxy; each occurrence of R ^g is independently selected from the group consisting of: • C3-10 cycloalkyl or C3-10 cycloalkenyl, each of which is optionally substituted with from 1-4 substituents independently selected from the group consisting of oxo and R ^c ; • heterocyclyl or heterocycloalkenyl including from 3-10 ring atoms, wherein from 1-3 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R ^d ), O, and S(O)0-2, and wherein the heterocyclyl or heterocycloalkenyl is optionally substituted with from 1-4 substituents independently selected from the group consisting of oxo and R ^c ; • heteroaryl including from 5-10 ring atoms, wherein from 1-4 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R ^d ), O, and S(O)0-2, and wherein the heteroaryl is optionally substituted with from 1-4 R ^c ; and • C6-10 aryl optionally substituted with from 1-4 R ^c ; each occurrence of L ^g is independently selected from the group consisting of: -O-, -NH-, -NR ^d , -S(O)0-2, C(O), and C1-3 alkylene optionally substituted with from 1-3 R ^a ; each g is independently 1, 2, or 3; each R ^g2 is a divalent R ^g group; and each occurrence of R’ and R’’ is independently selected from the group consisting of: H; -OH; and C1-4 alkyl. In another aspect, this disclosure features methods of preparing a compound of Formula (I), or a pharmaceutically acceptable salt thereof, the method comprising contacting a compound of formula (II) with a compound of formula (III), wherein Y is selected from –OH or –NH2; Z is selected from • –C(=O)H; or • –CH(R)2 wherein each R independently selected from halo, alkoxy, OH or SO3M (M = Li, Na, K or NH4 ⁺ ), provided that when one R is OH, the other R cannot be halo, alkoxy or OH; R ^1c is selected from H, and R ^d ; each of R ^2a , R ^2b , R ^3a , and R ^3b is independently selected from the group consisting of: H; halo; -OH; -C(O)OH or –C(O)NH2; -CN; -R ^b ; -L ^b -R ^b ; -C1-6 alkoxy or -C1-6 thioalkoxy, each optionally substituted with from 1-6 R ^a ; -NR ^e R ^f ; -R ^g ; and -(L ^g )g-R ^g ; two of variables R ^2a , R ^2b , R ^3a , and R ^3b , together with the Ring B ring atoms to which each is attached, form a fused saturated or unsaturated ring of 3-12 ring atoms; • wherein from 0-2 of the ring atoms are each an independently selected heteroatom (in addition to –N(R ^1c )- when –N(R ^1c )- forms part of the fused saturated or unsaturated ring), wherein each of the independently selected heteroatoms is selected from the group consisting of N, NH, N(R ^d ), O, and S(O)0-2; and • wherein the fused saturated or unsaturated ring of 3-12 ring atoms is optionally substituted with from 1-4 substituents independently selected from the group consisting of oxo, R ^c , and R ^W ; Ring A is R ^g ; R ⁴ is selected from the group consisting of: H and R ^d ; Ring C is selected from the group consisting of: • • wherein: o each X ^b is independently X, R ^c , or H; and o each X ^a is independently selected from the group consisting of: H, halo; cyano; C1-10 alkyl which is optionally substituted with from 1-6 independently selected R ^a ; C2-6 alkenyl; -S(O)1-2(C1-4 alkyl); -S(O)(=NH)(C1-4 alkyl); -NR ^e R ^f ; –OH; - S(O)1-2NR’R’’; -C1-4 thioalkoxy; -NO2; -C(=O)(C1-10 alkyl); -C(=O)O(C1-4 alkyl); -C(=O)OH; -C(=O)NR’R’’; and –SF5; • 2-pyridyl or 3-pyridyl, each optionally substituted with X and further optionally substituted with from 1-4 R ^c ; • 2-pyridonyl or 4-pyridonyl, each optionally substituted with X and further optionally substituted with from 1-4 R ^c , wherein the ring nitrogen atom is optionally substituted with R ^d ; • heteroaryl including 6 ring atoms, wherein from 2-4 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), and N(R ^d ), and wherein the heteroaryl is optionally substituted with X and further optionally substituted with from 1-4 R ^c ; • heteroaryl including 5 ring atoms, wherein from 1-4 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R ^d ), O, and S(O)0-2, and wherein the heteroaryl is optionally substituted with X and further optionally substituted with from 1-4 R ^c ; • bicyclic heteroaryl including 7-10 ring atoms, wherein from 1-4 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R ^d ), O, and S(O)0-2, and wherein the heteroaryl is optionally substituted with X and optionally substituted with from 1-4 substituents independently selected from the group consisting of oxo and R ⁷ ; • bicyclic C5-10 cycloalkyl or C5-10 cycloalkenyl, each of which is optionally substituted with X and is optionally substituted with from 1-4 substituents independently selected from the group consisting of oxo and R ⁷ ; • heterocyclyl or heterocycloalkenyl including from 5-10 ring atoms, wherein from 1-3 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R ^d ), O, and S(O)0-2, and wherein the heterocyclyl or heterocycloalkenyl is optionally substituted with X and optionally substituted with from 1-4 substituents independently selected from the group consisting of oxo and R ⁷ ; and • C10 or C14 aryl optionally substituted with X and optionally substituted with from 1-4 R ⁷ ; • wherein o ma is 0, 1, 2, or 3; o R ^8A is independently selected from halogen, hydroxy, nitro, cyano, C1-4 alkyl, C1-4 haloalkyl, C1-6 alkoxy, C3-6 cycloalkyl, C3-6 halocycloalkyl, R ^9A R ^10A N-, R ^11A -C(O)-NH-, R ^11A O-C(O)-NH-or R ^9A R ^10A N-C(O)-NH-, wherein said C1-6 alkoxy is optionally substituted one, two or three times, independently of each other, with halogen and is optionally substituted one time with hydroxy, C1-4 alkoxy, R ^9A R ^10A N-, C3-6 cycloalkyl, 4-to-7-membered heterocycloalkyl or phenyl, which is optionally substituted one or more R ^5A ; o R ^5A is selected from hydroxy, halogen, cyano, C1-4-alkyl, C1-4-alkoxy, C1-4 haloalkyl or C1-4 haloalkoxy; o R ^9A and R ^10A are each independently selected from hydrogen, C ^1-4 alkyl, C ^3-6 cycloalkyl, C1-4 haloalkyl, C3-6 halocycloalkyl or phenyl, wherein said phenyl group is optionally substituted, one or more times, independently of each other, with R ^5A ; or R ^9A and R ^10A together with the nitrogen atom to which they are attached form a 3- to 6-membered nitrogen containing heterocyclic ring, optionally containing one additional heteroatom or heteroatom containing group selected from O, NH or S, and which may be optionally substituted, one or more times, independently of each other, with R ^5A ; o R ^11A is independently selected from C1-4 alkyl, C3-6 cycloalkyl, C1-4 haloalkyl or C3-6 halocycloalkyl; • wherein o R ^5B is C2-5 alkyl optionally substituted with hydroxy, C1-4 alkoxy, R ^7B R ^8B N-, or phenyl, wherein the phenyl group is optionally substituted with one or more times with R ^5A ; or o R ^5B is R ^6B -CH2-; o R ^6B is selected from , or o R ^7B and R ^8B is independently selected from C1-3 alkyl, C1-3 haloalkyl; or o R ^7B and R ^8B together with the nitrogen atom to which they are attached form a 5- to 6-membered nitrogen containing heterocyclic ring, optionally containing one additional heteroatom or heteroatom containing group selected from O and –NH-, NH(C1-3 alkyl); o R ^9B is selected from hydrogen, C1-4 alkyl, or C1-3 haloalkyl; o R ^5A is selected from hydroxy, halogen, cyano, C1-4-alkyl, C1-4-alkoxy, C1-4 haloalkyl or C ^1-4 haloalkoxy; • wherein o R ^4C is selected from hydrogen or methyl; o R ^6C is selected from hydrogen, C1-3 alkyl, C1-3 haloalkyl; o nc is 0 or 1; o X ^C is NR ^7C or O; o Y ^C is NR ^8C or O; o R ^7C is methyl; o R ^8C is selected from methyl, 2,2,2-trifloethyl, or 2,2-difluoroethyl; o R ^5C is selected from hydrogen or methyl, wherein R ^5C being attached to any carbon atom of the ring comprising X ^C and Y ^C ; o mc is 0, 1, 2, or 3; • wherein o R ^4D is selected from hydrogen or methyl; o R ^5D is selected from the group consisting of (R/S)-2-oxetanyl, (S)-2-oxetanyl, 3-oxetanyl, (R/S)-2-azetidinyl, (S)-2-azetidinyl, 3-azetidinyl, each of which is optionally substituted one, two or three times with R ^6D and wherein each azetidinyl is substituted at the nitrogen with R ^8D ; OR o R ^5D is selected from the group consisting of and is selected from fluoro or C alkyl; o R ^6D 1-3 o md is selected from 0, 1, 2, or 3; o R ^7D is selected from hydrogen, C1-3 alkyl, or C1-3 haloalkyl; o X ^D is NR ^8D of O; o R ^8D is selected from C1-3 alkyl or C2-3 haloalkyl; X is X*, wherein X* is selected from halo, triflate, tosylate, or mesylate; or X is X ¹ ; each R ⁷ is an independently selected R ^c ; n is 0, 1, 2, or 3; X ¹ is selected from the group consisting of: (a) –O-L ¹ -R ⁵ ; and (b) ; L ¹ and L ² are independently selected from the group consisting of: a bond and C1-10 alkylene optionally substituted with from 1-6 R ^a ; R ⁵ is selected from the group consisting of: • heteroaryl including from 5-10 ring atoms, wherein from 1-4 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R ^d ), O, and S(O)0-2, and wherein the heteroaryl is optionally substituted with from 1-4 R ^c ; • C6-10 aryl optionally substituted with from 1-4 R ^c ; • C3-10 cycloalkyl or C3-10 cycloalkenyl, each optionally substituted with from 1-4 substituents each independently selected from the group consisting of: oxo and R ^c ; • , wherein Ring D is heterocyclylene or heterocycloalkenylene including from 3-10 ring atoms, wherein from 0-2 ring atoms (in addition to the ring nitrogen atom bonded to R ^X ) are heteroatoms, each independently selected from the group consisting of N, N(H), N(R ^d ), O, and S(O)0-2, and wherein the heterocyclylene or heterocycloalkenylene is optionally substituted with from 1-4 substituents each independently selected from the group consisting of: oxo and –R ^c ; • -S(O)0-2(C1-6 alkyl) which is optionally substituted with from 1-6 R ^a ; • -R ^W • -R ^g2 -R ^W or -R ^g2 -R ^Y ; • -L ⁵ -R ^g ; and • -L ⁵ -R ^g2 -R ^W or –L ⁵ -R ^g2 -R ^Y ; provided that when L ¹ is a bond, then R ⁵ is other than -S(O)0-2(C1-6 alkyl) which is optionally substituted with from 1-6 R ^a ; -L ⁵ -R ^g ; -L ⁵ -R ^g2 -R ^W ; or –L ⁵ -R ^g2 -R ^Y ; R ⁶ is selected from the group consisting of: • H; • halo; • -OH; • -NR ^e R ^f ; • -R ^g ; • -R ^w • -L ⁶ -R ^g ; • -R ^g2 -R ^W or -R ^g2 -R ^Y ; • -L ⁶ -R ^g2 -R ^W or -L ⁶ -R ^g2 -R ^Y ; and • -C1-6 alkoxy or -S(O)0-2(C1-6 alkyl), each optionally substituted with from 1-6 R ^a ; L ⁵ and L ⁶ are independently –O-, -S(O)0-2, -NH, or -N(R ^d )-; and R ^W is –L ^W -W, wherein L ^W is C(=O), S(O)1-2, OC(=O)*, NHC(=O)*, NR ^d C(=O)*, NHS(O)1-2*, or NR ^d S(O)1-2*, wherein the asterisk represents point of attachment to W, and W is C2-6 alkenyl; C2-6 alkynyl; or C3-10 allenyl, each of which is optionally substituted with from 1-3 R ^a and further optionally substituted with R ^g , wherein W is attached to L ^W via an sp ² or sp hybridized carbon atom, thereby providing an α, β-unsaturated system; and R ^X is C(=O)(C1-6 alkyl) or S(O)2(C1-6 alkyl), each of which is optionally substituted with from 1-6 R ^a ; and R ^Y is selected from the group consisting of: -R ^g and -(L ^g )g-R ^g . each occurrence of R ^a is independently selected from the group consisting of: –OH; - halo; –NR ^e R ^f ; C1-4 alkoxy; C1-4 haloalkoxy; -C(=O)O(C1-4 alkyl); -C(=O)(C1-4 alkyl); - C(=O)OH; -CONR’R’’; -S(O)1-2NR’R’’; -S(O)1-2(C1-4 alkyl); and cyano; each occurrence of R ^b is independently C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl, each of which is optionally substituted with from 1-6 R ^a ; each occurrence of L ^b is independently C(=O); C(=O)O; S(O)1-2; C(=O)NH*; C(=O)NR ^d *; S(O)1-2NH*; or S(O)1-2N(R ^d )*, wherein the asterisk represents point of attachment to R ^b ; each occurrence of R ^c is independently selected from the group consisting of: halo; cyano; C1-10 alkyl which is optionally substituted with from 1-6 independently selected R ^a ; C3-5 cycloalkyl; C2-6 alkenyl; C2-6 alkynyl; C1-4 alkoxy optionally substituted with C1-4 alkoxy or C1-4 haloalkoxy; C1-4 haloalkoxy; -S(O)1-2(C1-4 alkyl); -S(O)(=NH)(C1-4 alkyl); -NR ^e R ^f ; –OH; -S(O)1-2NR’R’’; -C1-4 thioalkoxy; -NO2; -C(=O)(C1-10 alkyl); -C(=O)O(C1- 4 alkyl); -C(=O)OH; -C(=O)NR’R’’; and –SF5; each occurrence of R ^d is independently selected from the group consisting of: C1-6 alkyl optionally substituted with from 1-3 independently selected R ^a or R ^g ; -C(O)(C1-4 alkyl); - C(O)O(C1-4 alkyl); -CONR’R’’; -S(O)1-2NR’R’’; - S(O)1-2(C1-4 alkyl); -OH; and C1-4 alkoxy; each occurrence of R ^e and R ^f is independently selected from the group consisting of: H; C3-5 cycloalkyl optionally substituted with from 1-3 C1-3 alkyl group; heterocyclyl including from 3-6 ring atoms, wherein from 1-3 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R ^d ), O, and S(O)0-2 optionally substituted with from 1-4 substituents independently selected from the group consisting of oxo and R ^c ; C1-6 alkyl optionally substituted with from 1-3 substituents each independently selected from the group consisting of NR’R’’, -OH, C1-6 alkoxy, C1-6 haloalkoxy, and halo; -C(O)(C1-4 alkyl); -C(O)O(C1-4 alkyl); -CONR’R’’; -S(O)1- 2NR’R’’; - S(O)1-2(C1-4 alkyl); -OH; and C1-4 alkoxy; each occurrence of R ^g is independently selected from the group consisting of: • C3-10 cycloalkyl or C3-10 cycloalkenyl, each of which is optionally substituted with from 1-4 substituents independently selected from the group consisting of oxo and R ^c ; • heterocyclyl or heterocycloalkenyl including from 3-10 ring atoms, wherein from 1-3 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R ^d ), O, and S(O)0-2, and wherein the heterocyclyl or heterocycloalkenyl is optionally substituted with from 1-4 substituents independently selected from the group consisting of oxo and R ^c ; • heteroaryl including from 5-10 ring atoms, wherein from 1-4 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R ^d ), O, and S(O)0-2, and wherein the heteroaryl is optionally substituted with from 1-4 R ^c ; and • C6-10 aryl optionally substituted with from 1-4 R ^c ; each occurrence of L ^g is independently selected from the group consisting of: -O-, -NH-, -NR ^d _, -S(O)0-2, C(O), and C1-3 alkylene optionally substituted with from 1-3 R ^a ; each g is independently 1, 2, or 3; each R ^g2 is a divalent R ^g group; and each occurrence of R’ and R’’ is independently selected from the group consisting of: H; -OH; and C1-4 alkyl. In another aspect, this disclosure features methods of preparing a compound of Formula (I), or a pharmaceutically acceptable salt thereof, the method comprising contacting a compound of formula (II) with a compound of formula (III), wherein Y is selected from –OH or –NH2; Z is selected from • –C(=O)H; or • –CH(R)2 wherein each R independently selected from halo, alkoxy, OH or SO3M (M = Li, Na, K or NH4 ⁺ ), provided that when one R is OH, the other R cannot be halo, alkoxy or OH; R ^1c is selected from H, and R ^d ; each of R ^2a , R ^2b , R ^3a , and R ^3b is independently selected from the group consisting of: H; halo; -OH; -C(O)OH or –C(O)NH2; -CN; -R ^b ; -L ^b -R ^b ; -C1-6 alkoxy or -C1-6 thioalkoxy, each optionally substituted with from 1-6 R ^a ; -NR ^e R ^f ; -R ^g ; and -(L ^g )g-R ^g ; two of variables R ^2a , R ^2b , R ^3a , and R ^3b , together with the Ring B ring atoms to which each is attached, form a fused saturated or unsaturated ring of 3-12 ring atoms; • wherein from 0-2 of the ring atoms are each an independently selected heteroatom (in addition to –N(R ^1c )- when –N(R ^1c )- forms part of the fused saturated or unsaturated ring), wherein each of the independently selected heteroatoms is selected from the group consisting of N, NH, N(R ^d ), O, and S(O)0-2; and • wherein the fused saturated or unsaturated ring of 3-12 ring atoms is optionally substituted with from 1-4 substituents independently selected from the group consisting of oxo, R ^c , and R ^W ; Ring A is R ^g ; R ⁴ is selected from the group consisting of: H and R ^d ; Ring C is selected from the group consisting of: • • wherein: o each X ^b is independently X, R ^c , or H; and o each X ^a is independently selected from the group consisting of: H, halo; cyano; C1-10 alkyl which is optionally substituted with from 1-6 independently selected R ^a ; C2-6 alkenyl; -S(O)1-2(C1-4 alkyl); -S(O)(=NH)(C1-4 alkyl); -NR ^e R ^f ; –OH; - S(O) ^1-2 NR’R’’; -C ^1-4 thioalkoxy; -NO ² ; -C(=O)(C ^1-10 alkyl); -C(=O)O(C ^1-4 alkyl); -C(=O)OH; -C(=O)NR’R’’; and –SF5; • 2-pyridyl or 3-pyridyl, each optionally substituted with X and further optionally substituted with from 1-4 R ^c ; • 2-pyridonyl or 4-pyridonyl, each optionally substituted with X and further optionally substituted with from 1-4 R ^c , wherein the ring nitrogen atom is optionally substituted with R ^d ; • heteroaryl including 6 ring atoms, wherein from 2-4 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), and N(R ^d ), and wherein the heteroaryl is optionally substituted with X and further optionally substituted with from 1-4 R ^c ; • heteroaryl including 5 ring atoms, wherein from 1-4 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R ^d ), O, and S(O)0-2, and wherein the heteroaryl is optionally substituted with X and further optionally substituted with from 1-4 R ^c ; • bicyclic heteroaryl including 7-10 ring atoms, wherein from 1-4 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R ^d ), O, and S(O)0-2, and wherein the heteroaryl is optionally substituted with X and optionally substituted with from 1-4 substituents independently selected from the group consisting of oxo and R ⁷ ; • bicyclic C5-10 cycloalkyl or C5-10 cycloalkenyl, each of which is optionally substituted with X and is optionally substituted with from 1-4 substituents independently selected from the group consisting of oxo and R ⁷ ; • heterocyclyl or heterocycloalkenyl including from 5-10 ring atoms, wherein from 1-3 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R ^d ), O, and S(O)0-2, and wherein the heterocyclyl or heterocycloalkenyl is optionally substituted with X and optionally substituted with from 1-4 substituents independently selected from the group consisting of oxo and R ⁷ ; and • C10 or C14 aryl optionally substituted with X and optionally substituted with from 1-4 R ⁷ ; X is X*, wherein X* is selected from halo, triflate, tosylate, or mesylate; or X is X ¹ ; each R ⁷ is an independently selected R ^c ; n is 0, 1, 2, or 3; X ¹ is selected from the group consisting of: (a) –O-L ¹ -R ⁵ ; and (b) ; L ¹ and L ² are independently selected from the group consisting of: a bond and C1-10 alkylene optionally substituted with from 1-6 R ^a ; R ⁵ is selected from the group consisting of: • heteroaryl including from 5-10 ring atoms, wherein from 1-4 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R ^d ), O, and S(O)0-2, and wherein the heteroaryl is optionally substituted with from 1-4 R ^c ; • C6-10 aryl optionally substituted with from 1-4 R ^c ; • C3-10 cycloalkyl or C3-10 cycloalkenyl, each optionally substituted with from 1-4 substituents each independently selected from the group consisting of: oxo and R ^c ; • , wherein Ring D is heterocyclylene or heterocycloalkenylene including from 3-10 ring atoms, wherein from 0-2 ring atoms (in addition to the ring nitrogen atom bonded to R ^X ) are heteroatoms, each independently selected from the group consisting of N, N(H), N(R ^d ), O, and S(O)0-2, and wherein the heterocyclylene or heterocycloalkenylene is optionally substituted with from 1-4 substituents each independently selected from the group consisting of: oxo and –R ^c ; • -S(O)0-2(C1-6 alkyl) which is optionally substituted with from 1-6 R ^a ; • -R ^W • -R ^g2 -R ^W or -R ^g2 -R ^Y ; • -L ⁵ -R ^g ; and • -L ⁵ -R ^g2 -R ^W or –L ⁵ -R ^g2 -R ^Y ; provided that when L ¹ is a bond, then R ⁵ is other than -S(O)0-2(C1-6 alkyl) which is optionally substituted with from 1-6 R ^a ; -L ⁵ -R ^g ; -L ⁵ -R ^g2 -R ^W ; or –L ⁵ -R ^g2 -R ^Y ; R ⁶ is selected from the group consisting of: • H; • halo; • -OH; • -NR ^e R ^f ; • -R ^g ; • -R ^w • -L ⁶ -R ^g ; • -R ^g2 -R ^W or -R ^g2 -R ^Y ; • -L ⁶ -R ^g2 -R ^W or -L ⁶ -R ^g2 -R ^Y ; and • -C1-6 alkoxy or -S(O)0-2(C1-6 alkyl), each optionally substituted with from 1-6 R ^a ; L ⁵ and L ⁶ are independently –O-, -S(O)0-2, -NH, or -N(R ^d )-; and R ^W is –L ^W -W, wherein L ^W is C(=O), S(O)1-2, OC(=O)*, NHC(=O)*, NR ^d C(=O)*, NHS(O)1-2*, or NR ^d S(O)1-2*, wherein the asterisk represents point of attachment to W, and W is C2-6 alkenyl; C2-6 alkynyl; or C3-10 allenyl, each of which is optionally substituted with from 1-3 R ^a and further optionally substituted with R ^g , wherein W is attached to L ^W via an sp ² or sp hybridized carbon atom, thereby providing an α, β-unsaturated system; and R ^X is C(=O)(C1-6 alkyl) or S(O)2(C1-6 alkyl), each of which is optionally substituted with from 1-6 R ^a ; and R ^Y is selected from the group consisting of: -R ^g and -(L ^g )g-R ^g . each occurrence of R ^a is independently selected from the group consisting of: –OH; - halo; –NR ^e R ^f ; C1-4 alkoxy; C1-4 haloalkoxy; -C(=O)O(C1-4 alkyl); -C(=O)(C1-4 alkyl); - C(=O)OH; -CONR’R’’; -S(O)1-2NR’R’’; -S(O)1-2(C1-4 alkyl); and cyano; each occurrence of R ^b is independently C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl, each of which is optionally substituted with from 1-6 R ^a ; each occurrence of L ^b is independently C(=O); C(=O)O; S(O)1-2; C(=O)NH*; C(=O)NR ^d *; S(O)1-2NH*; or S(O)1-2N(R ^d )*, wherein the asterisk represents point of attachment to R ^b ; each occurrence of R ^c is independently selected from the group consisting of: halo; cyano; C1-10 alkyl which is optionally substituted with from 1-6 independently selected R ^a ; C3-5 cycloalkyl; C2-6 alkenyl; C2-6 alkynyl; C1-4 alkoxy optionally substituted with C1-4 alkoxy or C1-4 haloalkoxy; C1-4 haloalkoxy; -S(O)1-2(C1-4 alkyl); -S(O)(=NH)(C1-4 alkyl); -NR ^e R ^f ; –OH; -S(O)1-2NR’R’’; -C1-4 thioalkoxy; -NO2; -C(=O)(C1-10 alkyl); -C(=O)O(C1- 4 alkyl); -C(=O)OH; -C(=O)NR’R’’; and –SF5; each occurrence of R ^d is independently selected from the group consisting of: C1-6 alkyl optionally substituted with from 1-3 independently selected R ^a or R ^g ; -C(O)(C1-4 alkyl); - C(O)O(C1-4 alkyl); -CONR’R’’; -S(O)1-2NR’R’’; - S(O)1-2(C1-4 alkyl); -OH; and C1-4 alkoxy; each occurrence of R ^e and R ^f is independently selected from the group consisting of: H; C3-5 cycloalkyl optionally substituted with from 1-3 C1-3 alkyl group; heterocyclyl including from 3-6 ring atoms, wherein from 1-3 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R ^d ), O, and S(O)0-2 optionally substituted with from 1-4 substituents independently selected from the group consisting of oxo and R ^c ; C1-6 alkyl optionally substituted with from 1-3 substituents each independently selected from the group consisting of NR’R’’, -OH, C1-6 alkoxy, C1-6 haloalkoxy, and halo; -C(O)(C1-4 alkyl); -C(O)O(C1-4 alkyl); -CONR’R’’; -S(O)1- 2NR’R’’; - S(O)1-2(C1-4 alkyl); -OH; and C1-4 alkoxy; each occurrence of R ^g is independently selected from the group consisting of: • C3-10 cycloalkyl or C3-10 cycloalkenyl, each of which is optionally substituted with from 1-4 substituents independently selected from the group consisting of oxo and R ^c ; • heterocyclyl or heterocycloalkenyl including from 3-10 ring atoms, wherein from 1-3 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R ^d ), O, and S(O)0-2, and wherein the heterocyclyl or heterocycloalkenyl is optionally substituted with from 1-4 substituents independently selected from the group consisting of oxo and R ^c ; • heteroaryl including from 5-10 ring atoms, wherein from 1-4 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R ^d ), O, and S(O)0-2, and wherein the heteroaryl is optionally substituted with from 1-4 R ^c ; and • C6-10 aryl optionally substituted with from 1-4 R ^c ; each occurrence of L ^g is independently selected from the group consisting of: -O-, -NH-, -NR ^d _, -S(O)0-2, C(O), and C1-3 alkylene optionally substituted with from 1-3 R ^a ; each g is independently 1, 2, or 3; each R ^g2 is a divalent R ^g group; and each occurrence of R’ and R’’ is independently selected from the group consisting of: H; -OH; and C1-4 alkyl. In another aspect, this disclosure features methods of preparing a compound of Formula (I), or a pharmaceutically acceptable salt thereof, the method comprising contacting a compound of formula (II) with a compound of formula (III), wherein Y is selected from –OH or –NH2; Z is selected from • –C(=O)H; or • –CH(R)2 wherein each R independently selected from halo, alkoxy, OH or SO3M (M = Li, Na, K or NH4 ⁺ ), provided that when one R is OH, the other R cannot be halo, alkoxy or OH; R ^1c is selected from H, and R ^d ; each of R ^2a , R ^2b , R ^3a , and R ^3b is independently selected from the group consisting of: H; halo; -OH; -C(O)OH or –C(O)NH2; -CN; -R ^b ; -L ^b -R ^b ; -C1-6 alkoxy or -C1-6 thioalkoxy, each optionally substituted with from 1-6 R ^a ; -NR ^e R ^f ; -R ^g ; and -(L ^g )g-R ^g ; two of variables R ^2a , R ^2b , R ^3a , and R ^3b , together with the Ring B ring atoms to which each is attached, form a fused saturated or unsaturated ring of 3-12 ring atoms; • wherein from 0-2 of the ring atoms are each an independently selected heteroatom (in addition to –N(R ^1c )- when –N(R ^1c )- forms part of the fused saturated or unsaturated ring), wherein each of the independently selected heteroatoms is selected from the group consisting of N, NH, N(R ^d ), O, and S(O)0-2; and • wherein the fused saturated or unsaturated ring of 3-12 ring atoms is optionally substituted with from 1-4 substituents independently selected from the group consisting of oxo, R ^c , and R ^W ; Ring A is R ^g ; R ⁴ is selected from the group consisting of: H and R ^d ; Ring C is selected from the group consisting of: • wherein o ma is 0, 1, 2, or 3; o R ^8A is independently selected from halogen, hydroxy, nitro, cyano, C1-4 alkyl, C1-4 haloalkyl, C1-6 alkoxy, C3-6 cycloalkyl, C3-6 halocycloalkyl, R ^9A R ^10A N-, R ^11A -C(O)-NH-, R ^11A O-C(O)-NH-or R ^9A R ^10A N-C(O)-NH-, wherein said C ^1-6 alkoxy is optionally substituted one, two or three times, independently of each other, with halogen and is optionally substituted one time with hydroxy, C1-4 alkoxy, R ^9A R ^10A N-, C3-6 cycloalkyl, 4-to-7-membered heterocycloalkyl or phenyl, which is optionally substituted one or more R ^5A ; o R ^5A is selected from hydroxy, halogen, cyano, C1-4-alkyl, C1-4-alkoxy, C1-4 haloalkyl or C1-4 haloalkoxy; o R ^9A and R ^10A are each independently selected from hydrogen, C1-4 alkyl, C3-6 cycloalkyl, C1-4 haloalkyl, C3-6 halocycloalkyl or phenyl, wherein said phenyl group is optionally substituted, one or more times, independently of each other, with R ^5A ; or R ^9A and R ^10A together with the nitrogen atom to which they are attached form a 3- to 6-membered nitrogen containing heterocyclic ring, optionally containing one additional heteroatom or heteroatom containing group selected from O, NH or S, and which may be optionally substituted, one or more times, independently of each other, with R ^5A ; o R ^11A is independently selected from C1-4 alkyl, C3-6 cycloalkyl, C1-4 haloalkyl or C3-6 halocycloalkyl; • , wherein o R ^5B is C2-5 alkyl optionally substituted with hydroxy, C1-4 alkoxy, R ^7B R ^8B N-, or phenyl, wherein the phenyl group is optionally substituted with one or more times with R ^5A ; or o R ^5B is R ^6B -CH2-; o R ^6B is selected from , or ; o R ^7B and R ^8B is independently selected from C1-3 alkyl, C1-3 haloalkyl; or o R ^7B and R ^8B together with the nitrogen atom to which they are attached form a 5- to 6-membered nitrogen containing heterocyclic ring, optionally containing one additional heteroatom or heteroatom containing group selected from O and –NH-, NH(C1-3 alkyl); o R ^9B is selected from hydrogen, C1-4 alkyl, or C1-3 haloalkyl; o R ^5A is selected from hydroxy, halogen, cyano, C1-4-alkyl, C1-4-alkoxy, C1-4 haloalkyl or C1-4 haloalkoxy; • wherein o R ^4C is selected from hydrogen or methyl; o R ^6C is selected from hydrogen, C1-3 alkyl, C1-3 haloalkyl; o nc is 0 or 1; o X ^C is NR ^7C or O; o Y ^C is NR ^8C or O; o R ^7C is methyl; o R ^8C is selected from methyl, 2,2,2-trifloethyl, or 2,2-difluoroethyl; o R ^5C is selected from hydrogen or methyl, wherein R ^5C being attached to any carbon atom of the ring comprising X ^C and Y ^C ; o mc is 0, 1, 2, or 3; • wherein o R ^4D is selected from hydrogen or methyl; o R ^5D is selected from the group consisting of (R/S)-2-oxetanyl, (S)-2-oxetanyl, 3-oxetanyl, (R/S)-2-azetidinyl, (S)-2-azetidinyl, 3-azetidinyl, each of which is optionally substituted one, two or three times with R ^6D and wherein each azetidinyl is substituted at the nitrogen with R ^8D ; OR o R ^5D is selected from the group consisting of and ; 6 ^D o R is selected from fluoro or C ^1-3 alkyl; o md is selected from 0, 1, 2, or 3; o R ^7D is selected from hydrogen, C1-3 alkyl, or C1-3 haloalkyl; o X ^D is NR ^8D of O; o R ^8D is selected from C1-3 alkyl or C2-3 haloalkyl; X is X*, wherein X* is selected from halo, triflate, tosylate, or mesylate; or X is X ¹ ; each R ⁷ is an independently selected R ^c ; n is 0, 1, 2, or 3; X ¹ is selected from the group consisting of: (a) –O-L ¹ -R ⁵ ; and (b) L ¹ and L ² are independently selected from the group consisting of: a bond and C1-10 alkylene optionally substituted with from 1-6 R ^a ; R ⁵ is selected from the group consisting of: • heteroaryl including from 5-10 ring atoms, wherein from 1-4 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R ^d ), O, and S(O)0-2, and wherein the heteroaryl is optionally substituted with from 1-4 R ^c ; • C6-10 aryl optionally substituted with from 1-4 R ^c ; • C3-10 cycloalkyl or C3-10 cycloalkenyl, each optionally substituted with from 1-4 substituents each independently selected from the group consisting of: oxo and R ^c ; • wherein Ring D is heterocyclylene or heterocycloalkenylene including from 3-10 ring atoms, wherein from 0-2 ring atoms (in addition to the ring nitrogen atom bonded to R ^X ) are heteroatoms, each independently selected from the group consisting of N, N(H), N(R ^d ), O, and S(O)0-2, and wherein the heterocyclylene or heterocycloalkenylene is optionally substituted with from 1-4 substituents each independently selected from the group consisting of: oxo and –R ^c ; • -S(O)0-2(C1-6 alkyl) which is optionally substituted with from 1-6 R ^a ; • -R ^W • -R ^g2 -R ^W or -R ^g2 -R ^Y ; • -L ⁵ -R ^g ; and • -L ⁵ -R ^g2 -R ^W or –L ⁵ -R ^g2 -R ^Y ; provided that when L ¹ is a bond, then R ⁵ is other than -S(O)0-2(C1-6 alkyl) which is optionally substituted with from 1-6 R ^a ; -L ⁵ -R ^g ; -L ⁵ -R ^g2 -R ^W ; or –L ⁵ -R ^g2 -R ^Y ; R ⁶ is selected from the group consisting of: • H; • halo; • -OH; • -NR ^e R ^f ; • -R ^g ; • -R ^w • -L ⁶ -R ^g ; • -R ^g2 -R ^W or -R ^g2 -R ^Y ; • -L ⁶ -R ^g2 -R ^W or -L ⁶ -R ^g2 -R ^Y ; and • -C1-6 alkoxy or -S(O)0-2(C1-6 alkyl), each optionally substituted with from 1-6 R ^a ; L ⁵ and L ⁶ are independently –O-, -S(O)0-2, -NH, or -N(R ^d )-; and R ^W is –L ^W -W, wherein L ^W is C(=O), S(O)1-2, OC(=O)*, NHC(=O)*, NR ^d C(=O)*, NHS(O)1-2*, or NR ^d S(O)1-2*, wherein the asterisk represents point of attachment to W, and W is C2-6 alkenyl; C2-6 alkynyl; or C3-10 allenyl, each of which is optionally substituted with from 1-3 R ^a and further optionally substituted with R ^g , wherein W is attached to L ^W via an sp ² or sp hybridized carbon atom, thereby providing an α, β-unsaturated system; and R ^X is C(=O)(C1-6 alkyl) or S(O)2(C1-6 alkyl), each of which is optionally substituted with from 1-6 R ^a ; and R ^Y is selected from the group consisting of: -R ^g and -(L ^g )g-R ^g . each occurrence of R ^a is independently selected from the group consisting of: –OH; - halo; –NR ^e R ^f ; C1-4 alkoxy; C1-4 haloalkoxy; -C(=O)O(C1-4 alkyl); -C(=O)(C1-4 alkyl); - C(=O)OH; -CONR’R’’; -S(O)1-2NR’R’’; -S(O)1-2(C1-4 alkyl); and cyano; each occurrence of R ^b is independently C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl, each of which is optionally substituted with from 1-6 R ^a ; each occurrence of L ^b is independently C(=O); C(=O)O; S(O)1-2; C(=O)NH*; C(=O)NR ^d *; S(O)1-2NH*; or S(O)1-2N(R ^d )*, wherein the asterisk represents point of attachment to R ^b ; each occurrence of R ^c is independently selected from the group consisting of: halo; cyano; C1-10 alkyl which is optionally substituted with from 1-6 independently selected R ^a ; C ^3-5 cycloalkyl; C ^2-6 alkenyl; C ^2-6 alkynyl; C ^1-4 alkoxy optionally substituted with C ^1-4 alkoxy or C1-4 haloalkoxy; C1-4 haloalkoxy; -S(O)1-2(C1-4 alkyl); -S(O)(=NH)(C1-4 alkyl); -NR ^e R ^f ; –OH; -S(O)1-2NR’R’’; -C1-4 thioalkoxy; -NO2; -C(=O)(C1-10 alkyl); -C(=O)O(C1- 4 alkyl); -C(=O)OH; -C(=O)NR’R’’; and –SF5; each occurrence of R ^d is independently selected from the group consisting of: C1-6 alkyl optionally substituted with from 1-3 independently selected R ^a or R ^g ; -C(O)(C1-4 alkyl); - C(O)O(C1-4 alkyl); -CONR’R’’; -S(O)1-2NR’R’’; - S(O)1-2(C1-4 alkyl); -OH; and C1-4 alkoxy; each occurrence of R ^e and R ^f is independently selected from the group consisting of: H; C3-5 cycloalkyl optionally substituted with from 1-3 C1-3 alkyl group; heterocyclyl including from 3-6 ring atoms, wherein from 1-3 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R ^d ), O, and S(O)0-2 optionally substituted with from 1-4 substituents independently selected from the group consisting of oxo and R ^c ; C1-6 alkyl optionally substituted with from 1-3 substituents each independently selected from the group consisting of NR’R’’, -OH, C1-6 alkoxy, C1-6 haloalkoxy, and halo; -C(O)(C1-4 alkyl); -C(O)O(C1-4 alkyl); -CONR’R’’; -S(O)1- 2NR’R’’; - S(O)1-2(C1-4 alkyl); -OH; and C1-4 alkoxy; each occurrence of R ^g is independently selected from the group consisting of: • C3-10 cycloalkyl or C3-10 cycloalkenyl, each of which is optionally substituted with from 1-4 substituents independently selected from the group consisting of oxo and R ^c ; • heterocyclyl or heterocycloalkenyl including from 3-10 ring atoms, wherein from 1-3 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R ^d ), O, and S(O)0-2, and wherein the heterocyclyl or heterocycloalkenyl is optionally substituted with from 1-4 substituents independently selected from the group consisting of oxo and R ^c ; • heteroaryl including from 5-10 ring atoms, wherein from 1-4 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R ^d ), O, and S(O)0-2, and wherein the heteroaryl is optionally substituted with from 1-4 R ^c ; and • C6-10 aryl optionally substituted with from 1-4 R ^c ; each occurrence of L ^g is independently selected from the group consisting of: -O-, -NH-, -NR ^d _, -S(O)0-2, C(O), and C1-3 alkylene optionally substituted with from 1-3 R ^a ; each g is independently 1, 2, or 3; each R ^g2 is a divalent R ^g group; and each occurrence of R’ and R’’ is independently selected from the group consisting of: H; -OH; and C1-4 alkyl. Ring A in formula (I) can be as defined anywhere herein. Variables R ^1c , R ^2a , R ^2b , R ^3a , and R ^3b in formula (I) can be as defined anywhere herein. Ring C in formula (I) can be as defined anywhere herein. In some embodiments, the contacting the compound of formula (II) with the compound of formula (III) is carried out in the presence of a nitrogen source. In certain embodiments, the nitrogen source is ammonia or derivative thereof. In certain embodiments, the nitrogen source is in the form of a salt. In certain embodiments, the nitrogen source is an ammonium salt. Non-limiting examples of the nitrogen sources include NH4OAc, NH3•H2O, NH4CO2H, NH4OBz, NH4Cl, (NH4)2SO4, (NH4)2HPO4, NH4H2PO4, NH4OTf, NH4HCO3, (NH4)2CO3, NH4CO2CF3, NH4BF4, ammonium citrate dibasic, NH4Br, ammonium carbamate, or any combination thereof. Other examples include primary alkyl and cycloalkyl amines, e.g., (C1-C6 alkyl)-NH2 and (C3-C6 cycloalkyl)-NH2. For example, the nitrogen source can be NH4OAc. In some embodiments, the molar ratio of the nitrogen source to the compound of formula (III) is from about 2:1 to about 8:1. In certain embodiments, the molar ratio of the nitrogen source to the compound of formula (III) is from about 4:1 to about 6:1. In certain embodiments, the molar ratio of the nitrogen source to the compound of formula (III) is about 4.5:1; 4.6:1; 4.7:1; 4.8:1; 4.9:1; 5:1; 5.1:1; 5.2:1; 5.3:1; 5.4:1; or 5.5:1, For example, the molar ratio of the nitrogen source to the compound of formula (III) can be about 5:1. In some embodiments an equivalent amount or an excess amount of the compound of formula (III) relative to the compound of formula (II) is employed. In certain embodiments, the molar ratio of the compound of formula (III) relative to the compound of formula (II) is from about 1:1 to about 3:1, e.g., about 1:1, 1.1:1, 1.2:1, 1.3:1, 1.4:1, 1.5:1, 1.6:1, 1.7:1, 1.8:1, 1.9:1, 2:1, 2.1:1, 2.2:1, 2.3:1, 2.4:1, 2.5:1, 2.6:1, 2.7:1, 2.8:1, 2.9:1, or about 3:1. In certain embodiments, the molar ratio of the compound of formula (III) relative to the compound of formula (II) is about 1.3:1 or about 1.5:1 or about 2:1. In certain embodiments, the compound of formula (III) is added portion-wise, e.g., over a period of from about 2 hours to about 4 hours. In some embodiments, contacting the compound of formula (II) with the compound of formula (III) is carried out in the presence of a suitable solvent (e.g., a suitable organic solvent). Mixtures of solvents (e.g., organic solvents) can also be employed. In some embodiments, the solvent is an aprotic solvent. In some embodiments, the aprotic solvent is a non-polar aprotic solvent. In certain embodiments, the non-polar aprotic solvent is an aromatic hydrocarbon solvent. Aromatic hydrocarbon solvents include, without limitation, toluene, anisole, xylenes (e.g., mixed xylenes (BTEX)), trifluorotoluene, benzene, chlorobenzene, 1, 2- dichlorobenzene, 1, 2-difluorobenzene, hexafluorobenzene, ethylbenzene, and high flash aromatic naphthas. For example, the aromatic hydrocarbon solvent can be toluene. In certain embodiments, the non-polar aprotic solvent is a non-aromatic hydrocarbon solvent. Non-aromatic hydrocarbon solvents include, without limitation, heptane, hexane, cyclohexane, methylcyclohexane, heptane, and isooctane. In some embodiments, the aprotic solvent is a polar aprotic solvent. Polar aprotic solvents include, without limitation, acetone, dichloromethane, cyclopentanone, methylisobutylketone, methylethylketone, EtOAc, isopropyl acetate, isobutyl acetate, glycerol diacetate, isoamyl acetate, tetrahydrofuran, dimethoxyethane, dioxane, N-methyl- 2-pyrrolidone, CPME, 1,4-dioxane, THF, acetonitrile, DMSO, 2-MeTHF, Methyl tert- butyl ether (MTBE), 2,5-dimethylisosorbide, and chloroform. In certain embodiments, the aprotic solvent is an ethereal solvent, e.g., tetrahydrofuran, dimethoxyethane, dioxane, CPME, 1,4-dioxane, or THF. In certain embodiments, the aprotic solvent is acetonitrile or DMSO. In some embodiments, the solvent is a protic solvent, e.g., a polar protic solvent, e.g., acetic acid. Other suitable protic (polar) solvents include t-amyl alcohol, t-Butanol, n-propanol, ethanol, methanol, water, i-propanol, n-BuOH, t-Butanol, ethylene glycol, 1-Butanol, i- Amyl alcohol, 1-heptanol, 1-octanol, and 1-propanol. In some embodiments, contacting the compound of formula (II) with the compound of formula (III) is carried out in the presence of a suitable mixture of two or more solvents, e.g., mixture of two solvents, e.g., a mixture of one or more (e.g., one) aromatic hydrocarbon solvents and one or more (e.g., one) ethereal solvents. For example, a mixture of toluene and dioxane (e.g., a 1:1 mixture of toluene and dioxane). In some embodiments, contacting the compound of formula (II) with the compound of formula (III) is carried out at a temperature sufficient to produce the compound of formula (I). Those of skill in the art will readily be able to ascertain an appropriate temperature, using the methods described herein in combination with the knowledge in the art. Preferably, the reaction temperatures are above ambient temperature, that is, above 25ºC., or above 35ºC, or above. For example, suitable temperatures for conversion to a compound of formula (I) are temperatures that are at or below the reflux temperature of the reaction solvent. In other embodiments, a suitable temperature for preparing a compound of formula (I) is a temperature that is below the reflux temperature of the reaction solvent. In certain embodiments, contacting the compound of formula (II) with the compound of formula (III) is carried out at a temperature of from about 80 ºC to 110 ºC; or from about 80 ºC to 100 ºC. (e.g., 90 ºC or 95 ºC); or from about 90 ºC to 110 ºC. (e.g., 100 ºC). In certain embodiments, contacting the compound of formula (II) with the compound of formula (III) is carried out at a temperature of from about 90 ºC to 100 ºC (e.g., 95 ºC). In certain embodiments, contacting the compound of formula (II) with the compound of formula (III) is carried out at a temperature of from about 80 ºC to 100 ºC (e.g., 85 ºC to 95 ºC; e.g., 90 ºC). In certain embodiments, contacting the compound of formula (II) with the compound of formula (III) is carried out at a temperature of from about 90 ºC to 110 ºC (e.g., 85 ºC to 95 ºC; e.g., 100 ºC). In certain embodiments, contacting the compound of formula (II) with the compound of formula (III) is carried out at a temperature of from about 20 ºC to about 80 ºC. (e.g., 20 ºC). Those of ordinary skill in the art, using the methods described herein in combination with the knowledge in the art, will be readily able to ascertain an appropriate amount of time for the conversion of the compounds of formula (II) and formula (III) to the compounds of formula (I). For example, the conversion can be conducted until the conversion is substantially complete, as determined by HPLC. In some embodiments, the amount of time for substantial conversion to compounds of formula III is about 24 hours or less. In certain embodiments, the amount of time for substantial conversion is less than 24 hours, for example, about 20, 18, 16, 14, 12, 10, or about 8 hours. In some embodiments, contacting the compound of formula (II) with the compound of formula (III) is carried out in the presence of one or more additives. Additives include, without limitation, Na2SO4, H2O, H2SO4, acetic acid, formic acid, Bi(OTf)3, PPh3, NH4OH, NH4OAc, PPTS, PTSA, pyridine or any combination thereof. In some embodiments, the contacting the compound of formula (II) with the compound of formula (III) is carried out in a sealed container filled with air. In some embodiments, the contacting the compound of formula (II) with the compound of formula (III) is carried out in a sealed container filled with inert gas (e.g., nitrogen). In some embodiments, the contacting the compound of formula (II) with the compound of formula (III) is carried out in an open container. In some embodiments, the contacting the compound of formula (II) with the compound of formula (III) is carried out in an open container connected to an inert gas (e.g., nitrogen) manifold. The method of any one of claims 1-48, wherein contacting the compound of formula (II) with the compound of formula (III) is carried out in the absence of an oxidizing agent; e.g., a peroxy acid, e.g., m-CPBA. Examples of formula (I) compounds that can be prepared by the methods described herein include, but are not limited to, those described generically and specifically in PCT/US2021/051504, filed on September 22, 2021; PCT/US2021/054191, filed on October 8, 2021; and PCT/US2021/057348, filed on October 8, 2021 Compounds of Formula (II) and Preparation Thereof In some embodiments, the methods further include contacting a compound of formula (IIa) with a compound of formula (IIb) to provide the compound of formula (II): In some embodiments, the compound of formula (IIb) is prepared by contacting a chlorinating agent with a compound of formula (IId): Formula (IId). Chlorinating agents include, without limitation, thionyl chloride, methanesulfonyl Chloride, trichloromethanesulfonyl chloride, tert-butyl hypochlorite, dichloromethyl methyl ether, methoxyacetyl chloride, oxalyl chloride, cyanuric chloride, N- chlorosuccinimide, 1,3-Dichloro5,5-dimethylhydantoin, sodium dichloroisocyanurate, trichloroisocyanuric acid, chloramine T trihydrate, PCl5, and POCl3. By way of example the compound of formula (IIb) can be prepared by contacting a compound of formula (IIc) with a compound of formula (IId): Formula (IIc) Formula (IId). In some embodiments, Y in formula (II) is OH. In some embodiments, Y in formula (II) is NH2. Ring A can be as defined anywhere herein. Variables R ^1c , R ^2a , R ^2b , R ^3a , and R ^3b can be as defined anywhere herein. An exemplary formula (II) compound is: . Compounds of Formula (III) and Preparation Thereof In some embodiments, Z in formula (III) is –C(=O)H. In some embodiments, Z in formula (III) is -CH(R)2-. In certain embodiments, each R is halo (e.g., bromo). For example, Z can be –CH(Br)2. In other embodiments, each R is alkoxy (e.g., OCH3). For example, Z can be –CH(OCH3)2. In still other embodiments, one of R is OH, and the other R is SO3-M ⁺ (M+ = Li, Na, K or NH4 ⁺ ). For example, Z can be –CH(OCH3)(SO3-Na ⁺ ). In some embodiments of formula (III), X is X*. In certain embodiments, formula (III) is further substituted with a substituent reactive in Sonogashira coupling reactions, e.g., I, Br, Cl, F, triflate, tosylate, -C(O)Cl, and arylsulfonium triflate salts such as triarylsulfonium triflate salts, alkyl(diaryl)sulfonium triflate salts, and aryl(dialkyl)sulfonium triflate salts. In certain embodiments, the X* is halo, e.g., bromo. In some embodiments of formula (III), X is X ¹ . In certain embodiments, X ¹ is In certain embodiments, when formula (III) is substituted with is a bond. In certain embodiments, when formula (III) is substituted with ⁶ R is –R ^g2 -R ^W . In certain of the foregoing embodiments, –R ⁶ is , wherein Ring D is heterocyclylene including from 3-10 ring atoms, wherein from 0-2 ring atoms (in addition to the ring nitrogen atom bonded to R ^W ) are heteroatoms, each independently selected from the group consisting of N, N(H), N(R ^d ), O, and S(O)0-2, and wherein the heterocyclylene is optionally substituted with from 1-3 substituents each independently selected from the group consisting of: oxo and –R ^c ; optionally wherein -R ⁶ is a monocyclic heterocyclylene ring including from 3-10 ring atoms as defined above with a nitrogen atom bonded to R ^W (e.g., , such as or , such as or ); optionall ⁶ y wherein -R is a bicyclic heterocyclylene ring including from 3-10 ring atoms as defined above with a nitrogen atom bonded to R ^W (e.g. ; or , such as or ; or , such as or ; or , such as , or ). In certain of these embodiments, –R ⁶ is optionally substituted with from 1-2 R ^c , wherein x1 and x2 are each independently 0, 1, or 2. In certain embodiments, x1 = 0, and x2 = 0; or x1 = 0, and x2 = 1; or x1 = 0, and x2 = 2. As non-limiting examples when R ⁶ is ⁶ can be selected from the group consisting of: , such as or ; , such as or ; , such as or ; , such as or , and , such as or . Ring C in formula (III) can be as defined anywhere herein. Compounds of formula (III) can be prepared by conventional methods known to those of skill in the art and/or can be obtained commercially. An exemplary formula (III) compound is: . As the skilled person will appreciate, performing the methods described herein with formula (III) compounds, in which X is X* is expected to also produce formula (I) compounds, in which X is X*. Accordingly, the methods described herein further include converting the resultant formula (I) compounds, in which X is X* to formula (I) compounds, in which X is X ¹ . Reagents and conditions for converting the resultant formula (I) compounds, in which X is X* to formula (I) compounds, in which X is X ¹ will be apparent to the skilled artisan and representative syntheses are provided in the Examples section. Variables R ^1c , R ^2a , R ^2b , R ^3a , and R ^3b In some embodiments, Y is –OH. In some embodiments, R ^1c is a protecting group. Protecting groups include, without limitation, t-Butyloxycarbonyl(Boc), Benzyloxycarbonyl (Z), 9-Fluorenylmethoxycarbonyl (Fmoc), Allyloxycarbonyl (Alloc), Trityl (Trt), acetyl, benzyl, and p-Nitrobenzyloxycarbonyl (pNZ). In certain embodiments, R ^1c together with the nitrogen atom to which it is attached forms a carbamate. For example, R ^1c can be a Boc group. In certain of these embodiments, the methods further include removing the protecting group from the compound of formula (I), e.g., using conventional deprotection conditions know to those of skill in the art or by conducting the reaction to form the compound of formula (I) at an elevated temperature (e.g., 120ºC). In some embodiments, R ^1c is H. In some embodiments, each of R ^2a , R ^2b , R ^3a , and R ^3b is independently selected from the group consisting of: H; halo; -OH; -C(O)OH or –C(O)NH2; -CN; -R ^b ; -L ^b -R ^b ; - C1-6 alkoxy or -C1-6 thioalkoxy, each optionally substituted with from 1-6 R ^a ; -NR ^e R ^f ; - R ^g ; and -(L ^g )g-R ^g . In certain of these embodiments, one of R ^2a , R ^2b , R ^3a , and R ^3b is independently selected from the group consisting of: halo; -OH; -C(O)OH or –C(O)NH2; -CN; -R ^b ; -L ^b - R ^b ; -C1-6 alkoxy or -C1-6 thioalkoxy, each optionally substituted with from 1-6 R ^a ; -NR ^e R ^f ; -R ^g ; and -(L ^g )g-R ^g ; and the other of R ^2a , R ^2b , R ^3a , and R ^3b is H. In some embodiments, two of variables R ^2a , R ^2b , R ^3a , and R ^3b , together with the Ring B ring atoms to which each is attached, form a fused saturated or unsaturated ring of 3-12 ring atoms. In some embodiments, each of R ^2a , R ^2b , R ^3a , and R ^3b is H. In some embodiments, each of the foregoing definitions of R ^1c , R ^2a , R ^2b , R ^3a , and R ^3b apply to compounds of formula (II). In some embodiments, each of the foregoing definitions of R ^1c , R ^2a , R ^2b , R ^3a , and R ^3b apply to compounds of formula (I). Ring A In some embodiments, ring A is C6-10 aryl optionally substituted with from 1-4 R ^c . In certain embodiments, ring A is phenyl optionally substituted with from 1-4 R ^c . For example, ring A can be phenyl substituted with from 1-2 R ^c . In certain embodiments, Ring A is ), wherein each R ^cB is an independently selected R ^c . In certain embodiments, each R ^cB is independently selected from the group consisting of: -halo, such as -Cl and -F; -CN; C1-4 alkoxy; C1-4 haloalkoxy; C1-3 alkyl; and C1-3 alkyl substituted with from 1-6 independently selected halo. In certain embodiments, Ring A is , wherein R ^cB1 is R ^c ; and R ^cB2 is H or R ^c . In certain of these embodiments, R ^cB1 is halo (e.g., –F or –Cl (e.g., –F)). In certain embodiments, R ^cB2 is C1-4 alkoxy or C1-4 haloalkoxy (e.g., C1-4 alkoxy (e.g., methoxy)). As non-limiting examples of the foregoing embodiments, Ring A can be or . In some embodiments, each of the foregoing definitions of ring A apply to compounds of formula (II). In some embodiments, each of the foregoing definitions of ring A apply to compounds of formula (I). Ring C In some embodiments, Ring C is In some embodiments, Ring C is , wherein: o each X ^b is independently X, R ^c , or H; and o each X ^a is independently selected from the group consisting of: H, halo; cyano; C1-10 alkyl which is optionally substituted with from 1-6 independently selected R ^a ; C2-6 alkenyl; -S(O)1-2(C1-4 alkyl); -S(O)(=NH)(C1-4 alkyl); -NR ^e R ^f ; –OH; - S(O)1-2NR’R’’; -C1-4 thioalkoxy; -NO2; -C(=O)(C1-10 alkyl); -C(=O)O(C1-4 alkyl); -C(=O)OH; -C(=O)NR’R’’; and –SF5. In some embodiments, Ring C is 2-pyridyl or 3-pyridyl, each optionally substituted with X and further optionally substituted with from 1-4 R ^c . In some embodiments, Ring C is 2-pyridonyl or 4-pyridonyl, each optionally substituted with X and further optionally substituted with from 1-4 R ^c , wherein the ring nitrogen atom is optionally substituted with R ^d . In some embodiments, Ring C is heteroaryl including 6 ring atoms, wherein from 2-4 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), and N(R ^d ), and wherein the heteroaryl is optionally substituted with X and further optionally substituted with from 1-4 R ^c . In certain embodiments, Ring C is further optionally substituted with X, wherein each R ^cA is an independently selected R ^c ; and n is 0, 1, or 2. As a non-limiting example of the foregoing embodiments, Ring C can be , such as (e.g., ). In certain foregoing embodiments, n is 0 and R ^cA is C1-10 alkyl optionally substituted with from 1-6 independently selected R ^a , e.g., C1-3 alkyl optionally substituted with from 1-3 independently selected halo. As a non-limiting example, Ring C can be . In some embodiments, Ring C is heteroaryl including 5 ring atoms, wherein from 1-4 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R ^d ), O, and S(O)0-2, and wherein the heteroaryl is optionally substituted with X and further optionally substituted with from 1-4 R ^c . In some embodiments, Ring C is bicyclic heteroaryl including 7-10 ring atoms, wherein from 1-4 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R ^d ), O, and S(O)0-2, and wherein the heteroaryl is substituted with X and optionally substituted with from 1-4 substituents independently selected from the group consisting of oxo and R ⁷ . In some embodiments, Ring C is bicyclic heteroaryl including 7-10 ring atoms, wherein from 1-4 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R ^d ), O, and S(O)0-2, and wherein the heteroaryl is optionally substituted with X and optionally substituted with from 1-4 substituents independently selected from the group consisting of oxo and R ⁷ . In some embodiments, Ring C is bicyclic C5-10 cycloalkyl or C5-10 cycloalkenyl, each of which is substituted with X and is optionally substituted with from 1-4 substituents independently selected from the group consisting of oxo and R ⁷ . In some embodiments, Ring C is bicyclic C5-10 cycloalkyl or C5-10 cycloalkenyl, each of which is optionally substituted with X and is optionally substituted with from 1-4 substituents independently selected from the group consisting of oxo and R ⁷ . In some embodiments, Ring C is heterocyclyl or heterocycloalkenyl including from 5-10 ring atoms, wherein from 1-3 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R ^d ), O, and S(O)0-2, and wherein the heterocyclyl or heterocycloalkenyl is substituted with X and optionally substituted with from 1-4 substituents independently selected from the group consisting of oxo and R ⁷ . In some embodiments, Ring C is heterocyclyl or heterocycloalkenyl including from 5-10 ring atoms, wherein from 1-3 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R ^d ), O, and S(O)0-2, and wherein the heterocyclyl or heterocycloalkenyl is optionally substituted with X and optionally substituted with from 1-4 substituents independently selected from the group consisting of oxo and R ⁷ . In some embodiments, Ring C is selected from the group consisting of: • wherein o ma is 0, 1, 2, or 3; o R ^8A is independently selected from halogen, hydroxy, nitro, cyano, C1-4 alkyl, C1-4 haloalkyl, C1-6 alkoxy, C3-6 cycloalkyl, C3-6 halocycloalkyl, R ^9A R ^10A N-, R ^11A -C(O)-NH-, R ^11A O-C(O)-NH-or R ^9A R ^10A N-C(O)-NH-, wherein said C1-6 alkoxy is optionally substituted one, two or three times, independently of each other, with halogen and is optionally substituted one time with hydroxy, C1-4 alkoxy, R ^9A R ^10A N-, C3-6 cycloalkyl, 4-to-7-membered heterocycloalkyl or phenyl, which is optionally substituted one or more R ^5A ; o R ^5A is selected from hydroxy, halogen, cyano, C1-4-alkyl, C1-4-alkoxy, C1-4 haloalkyl or C1-4 haloalkoxy; o R ^9A and R ^10A are each independently selected from hydrogen, C1-4 alkyl, C3-6 cycloalkyl, C1-4 haloalkyl, C3-6 halocycloalkyl or phenyl, wherein said phenyl group is optionally substituted, one or more times, independently of each other, with R ^5A ; or R ^9A and R ^10A together with the nitrogen atom to which they are attached form a 3- to 6-membered nitrogen containing heterocyclic ring, optionally containing one additional heteroatom or heteroatom containing group selected from O, NH or S, and which may be optionally substituted, one or more times, independently of each other, with R ^5A ; o R ^11A is independently selected from C1-4 alkyl, C3-6 cycloalkyl, C1-4 haloalkyl or C ^3-6 halocycloalkyl; • , wherein o R ^5B is C2-5 alkyl optionally substituted with hydroxy, C1-4 alkoxy, R ^7B R ^8B N-, or phenyl, wherein the phenyl group is optionally substituted with one or more times with R ^5A ; or o R ^5B is R ^6B -CH2-; o R ^6B is selected from , or o R ^7B and R ^8B is independently selected from C1-3 alkyl, C1-3 haloalkyl; or o R ^7B and R ^8B together with the nitrogen atom to which they are attached form a 5- to 6-membered nitrogen containing heterocyclic ring, optionally containing one additional heteroatom or heteroatom containing group selected from O and –NH-, NH(C1-3 alkyl); o R ^9B is selected from hydrogen, C1-4 alkyl, or C1-3 haloalkyl; o R ^5A is selected from hydroxy, halogen, cyano, C1-4-alkyl, C1-4-alkoxy, C1-4 haloalkyl or C1-4 haloalkoxy; • , wherein o R ^4C is selected from hydrogen or methyl; o R ^6C is selected from hydrogen, C1-3 alkyl, C1-3 haloalkyl; o nc is 0 or 1; o X ^C is NR ^7C or O; o Y ^C is NR ^8C or O; o R ^7C is methyl; o R ^8C is selected from methyl, 2,2,2-trifloethyl, or 2,2-difluoroethyl; o R ^5C is selected from hydrogen or methyl, wherein R ^5C being attached to any carbon atom of the ring comprising X ^C and Y ^C ; o mc is 0, 1, 2, or 3; • wherein o R ^4D is selected from hydrogen or methyl; o R ^5D is selected from the group consisting of (R/S)-2-oxetanyl, (S)-2-oxetanyl, 3-oxetanyl, (R/S)-2-azetidinyl, (S)-2-azetidinyl, 3-azetidinyl, each of which is optionally substituted one, two or three times with R ^6D and wherein each azetidinyl is substituted at the nitrogen with R ^8D ; OR o R ^5D is selected from the group consisting of and o R ^6D is selected from fluoro or C1-3 alkyl; o md is selected from 0, 1, 2, or 3; o R ^7D is selected from hydrogen, C1-3 alkyl, or C1-3 haloalkyl; o X ^D is NR ^8D of O; o R ^8D is selected from C1-3 alkyl or C2-3 haloalkyl; In some embodiments, Ring C is C10 or C14 aryl substituted with X and optionally substituted with from 1-4 R ⁷ . In some embodiments, each of the foregoing definitions of ring A apply to compounds of formula (III). In some embodiments, each of the foregoing definitions of ring A apply to compounds of formula (II). In some embodiments, each of the foregoing definitions of ring A apply to compounds of formula (I). The compounds, intermediates, and reagents disclosed herein can be prepared in a variety of ways in addition to those described herein, using, e.g., commercially available starting materials, compounds known in the literature, or from readily prepared intermediates, by employing standard synthetic methods and procedures either known to those skilled in the art, or in light of the teachings herein. The synthesis of the compounds disclosed herein can be achieved by generally following the schemes and Examples provided below, with modification for specific desired substituents. Standard synthetic methods and procedures for the preparation of organic molecules and functional group transformations and manipulations can be obtained from the relevant scientific literature or from standard textbooks in the field. Although not limited to any one or several sources, classic texts such as R. Larock, Comprehensive Organic Transformations, VCH Publishers (1989); L. Fieser and M. Fieser, Fieser and Fieser's Reagents for Organic Synthesis, John Wiley and Sons (1994); Smith, M. B., March, J., March' s Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 5th edition, John Wiley & Sons: New York, 2001 ; and Greene, T.W., Wuts, P.G. M., Protective Groups in Organic Synthesis, 3rd edition, John Wiley & Sons: New York, 1999, are useful and recognized reference textbooks of organic synthesis known to those in the art. The following descriptions of synthetic methods are designed to illustrate, but not to limit, general procedures for the preparation of compounds of the present disclosure. The synthetic processes disclosed herein can tolerate a wide variety of functional groups; therefore, various substituted starting materials can be used. The processes generally provide the desired final compound at or near the end of the overall process, although it may be desirable in certain instances to further convert the compound to a pharmaceutically acceptable salt thereof. Compounds described herein can be isolated/purified using conventional methods know to those skilled in the art, e.g., column chromatography, crystallization, HPLC (e.g., chiral HPLC). Examples A number of embodiments of the invention have been described. Nevertheless, it will be understood that various modifications may be made without departing from the spirit and scope of the invention. Accordingly, other embodiments are within the scope of the following claims. Example 1. Synthesis of tert-butyl 2-(3-bromopyridin-4-yl)-3-((3-chloro-2- methoxyphenyl)amino)-4-oxo-1,4,6,7-tetrahydro-5H-pyrrolo[3,2 -c]pyridine-5- carboxylate A suspension of 3-bromopyridine-4-carbaldehyde (3.38 g, 18.2 mmol, 1.5 equiv) in dioxane (37.5 mL)/dioxane (37.5 mL) was stirred under heating (in a 80 °C mantle) until the aldehyde had dissolved. The resulting solution was then added dropwise by syringe pump over 3.0 hours to a 250 mL round-bottom flask containing a 95 °C mixture of tert- butyl 3-[(3-chloro-2-methoxyphenyl)carbamothioyl]-2,4-dioxopiperid ine-1-carboxylate (5.00 mg, 12.1 mmol, 1.0 equiv) and NH4OAc (4.67 g, 60.6 mmol, 5.0 equiv) in toluene (50.0 mL) under an atmosphere of nitrogen. The mixture was then stirred for 21 hours at that temperature (total reaction time 24 h). The reaction mixture was quenched with saturated aqueous NaHCO3 (100 mL) and diluted with MTBE (50 mL). The phases were separated and the aqueous layer extracted with MTBE (50 mL). The combined organic extracts were washed with saturated aqueous NaHCO3 (50 mL) and brine (50 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with n-heptane / EtOAc (3:1 to 0:1) to afford tert-butyl 2-(3-bromopyridin-4-yl)-3-((3-chloro-2-methoxyphenyl)amino)- 4-oxo-1,4,6,7- tetrahydro-5H-pyrrolo[3,2-c]pyridine-5-carboxylate (3.03 g, 45.6% yield) as a yellow solid. LCMS (ES, m/z): [M+H] ⁺ : 547/549; ¹ H NMR (400 MHz, CDCl3) δ 9.39 (s, 1H), 8.64 (s, 1H), 8.17 (d, J = 5.4 Hz, 1H), 7.84 (s, 1H), 7.28 (d, J = 5.3 Hz, 1H), 6.70 (dd, J = 8.1, 1.4 Hz, 1H), 6.54 (t, J = 8.1 Hz, 1H), 6.15 (dd, J = 8.2, 1.5 Hz, 1H), 4.14 (t, J = 6.3 Hz, 2H), 4.00 (s, 3H), 3.01 (t, J = 6.4 Hz, 2H), 1.56 (s, 9H). Example 2. Synthesis of tert-butyl 5-((3-chloro-2-methoxyphenyl)carbamothioyl)-4- hydroxy-6-oxo-3,6-dihydropyridine-1(2H)-carboxylate thiophosgene (6.08 mL, 79.3 mmol, 1.0 equiv) was added dropwise to a mixture of 3- chloro-2-methoxyaniline (12.5 g, 79.3 mmol, 1.0 equiv) in DCM (125 mL)/saturated aqueous NaHCO3 (125 mL) at 0 °C and the mixture stirred at that temperature for 3 hours. The layers were separated and the organic layer washed with saturated aqueous NaHCO3 and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to afford 1- chloro-3-isothiocyanato-2-methoxybenzene (16.2 g, quant. yield) as a brown oil. DBU (17.2 mL, 115 mmol, 1.5 equiv) was added dropwise to a stirred suspension of tert- butyl 2,4-dioxopiperidine-1-carboxylate (16.4 g, 76.9 mmol, 1.0 equiv) and 1-chloro-3- isothiocyanato-2-methoxybenzene (16.2 g, 76.9 mmol, 1.0 equiv) in MeCN (375 mL) at room temperature and the reaction mixture stirred for 20 hours. The reaction mixture was diluted with ice water (100 mL) and HCl (1 M, 115 mL, 115 mmol, 1.5 equiv) was added to reach pH 6. The mixture was stirred for 15 minutes and then filtered to give 24 g of filter cake (86% purity).1 g (x 2) of the filter cake was taken and slurried in MeCN (4 mL) or EtOAc (2 mL) at room temperature overnight and then filtered to give material with >99% purity, with more material recovered from the MeCN slurry than EtOAc (0.70 g vs 0.45 g). The remaining cake (22 g) was slurried in 4 volumes (88 mL) of MeCN for 4 hours, filtered, and dried overnight in a vacuum oven at 50 °C to afford tert-butyl 3-[(3-chloro-2- methoxyphenyl)carbamothioyl]-2,4-dioxopiperidine-1-carboxyla te (19.0 g, 59.8%) as a white solid. All of the filtrates were combined and purified by silica gel column chromatography, eluted with n-heptane / EtOAc (4:1 to 0:1) to afford tert-butyl 3-[(3- chloro-2-methoxyphenyl)carbamothioyl]-2,4-dioxopiperidine-1- carboxylate (4.54 g, 14.0%) as an off-white solid. LCMS (ES, m/z): [M-H]-: 411, [M+H] ⁺ : 313 (des-Boc); ¹ H NMR (400 MHz, CDCl3) δ 13.67 (s, 1H), 7.78 (d, J = 8.2 Hz, 1H), 7.32 (d, J = 8.2 Hz, 1H), 7.09 (td, J = 8.0, 2.5 Hz, 1H), 3.86 (m, 5H), 2.82 (t, J = 6.9 Hz, 2H). Example 3. Synthesis of sodium (3-bromopyridin-4-yl)(hydroxy)methanesulfonate A solution of NaHSO3 (565 mg, 5.43 mmol, 1.01 equiv) in water (1.8 mL) was added dropwise to a mixture of 3-bromopyridine-4-carbaldehyde (1.00 g, 5.38 mmol, 1 equiv) in EtOH (10 mL). The reaction mixture was stirred at room temperature for 2 hours and a solid had formed. EtOH (5 mL) was added and the mixture stirred for another 5 minutes and then filtered. The filter cake was washed with EtOH (2 × 2.5 mL) and dried in a vacuum oven overnight to afford sodium (3-bromopyridin-4-yl)(hydroxy)methanesulfonate (1.43 g, 91.7% yield) as a white solid.. LCMS (ESI, m/z): [M-Na] ^– 266/268; ¹ H NMR (400 MHz, DMSO-d6) δ 8.59 (s, 1H), 8.44 (d, J = 5.0 Hz, 1H), 7.64 (d, J = 5.0 Hz, 1H), 6.38 (d, J = 6.0 Hz, 1H), 5.29 (d, J = 6.0 Hz, 1H). Example 4. Synthesis of tert-butyl 2-(3-bromopyridin-4-yl)-3-[(3-chloro-2- methoxyphenyl)amino]-4-oxo-1H,6H,7H-pyrrolo[3,2-c]pyridine-5 -carboxylate An oven-dried vial was charged with tert-butyl 3-[(3-chloro-2- methoxyphenyl)carbamothioyl]-4-hydroxy-2-oxo-5,6-dihydropyri dine-1-carboxylate Boc-3 (50 mg, 0.121 mmol, 1 equiv) and ammonium acetate (46.7 mg, 0.61 mmol, 5 equiv.). Toluene (1 mL) was added and the formed suspension was heated at 95 °C. Sodium (3-bromopyridin-4-yl)(hydroxy)methanesulfonate 18 (52.7 mg, 0.18 mmol, 1.5 equiv.) was added in five portions in a period of 2.5 h (0.3 equiv. every 30 minutes) and the reaction mixture was then stirred overnight (16-18 h) at 95 °C. An aliquot was then taken and analyzed by LCMS and HPLC to give the following results: LCMS: 44% Boc-8, 22% Boc-3 HPLC (toluene peak deleted): 60% Boc-8, 31% Boc-3 Example 5. Representative Procedure 1 (GP1) for the synthesis of compounds of formula (II) DBU (1.50 eq) was added to a stirred suspension of β-ketoamide (formula (IIa)) (1.00 eq) and isothiocyanate (formula (IIb)) (1.00 eq) in anhydrous acetonitirile (0.470 m) under N ² atmosphere and the resulting mixture was stirred at ambient temperature for 20 h. The reaction was quenched with HCl (1.00 m) to pH 6, diluted with water and then extracted with EtOAc or DCM (3 × 50 mL). The combined organic extracts were washed with saturated aqueous NaHCO3 and brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The crude residue was purified by silica gel chromatography to provide the compound (formula (II)). Example 6. Representative Procedure 2 (GP2) for the synthesis of compounds of formula (I) An oven-dried vial was charged with the compound of formula (II) (1.00 eq) and NH4OAc (5.00 eq), and was evacuated and backfilled with N2 three times. Anhydrous toluene (10.0 vol) was added, and the reaction was heated to 90 °C. A premade solution of compound of formula (III) (1.50 eq) in anhydrous 1,4-dioxane (10.0 vol) was then added dropwise over 2.5 h with a syringe pump and the resulting mixture was stirred for 18 h at 90 °C. The reaction was cooled to ambient temperature and directly concentrated under reduced pressure. The crude residue was purified by silica gel chromatography to provide the compound of formula (I). Example 7. GP2 Reaction conditions

A. Starting Material: enamine 8 ^{a a} Reaction conditions: 8 (0.144 mmol), 6a (0.144 mmol), NH4OAc (0.720 mmol), Solvent (1.0 mL), Temperature, 20 h. B. Starting Material: enol 5a ^{b b} Reaction conditions: 5a (0.144 mmol), 6a (0.144 mmol), NH4OAc (0.720 mmol), Solvent (1.0 mL), Temperature, 20 h. C. Variation of aldehyde equivalents ^{c c} Reaction conditions: 5a (0.144 mmol), 6a, NH4OAc (0.720 mmol), 1,4-dioxane (1.0 mL), 70 °C, 20 h. ^b Isolated yield in brackets. D. Variation of concentration, temperature, ammonium source, and additives ^{d d} Reaction conditions: 5a (0.144 mmol), 6a (0.216 mmol), NH3 source, Solvent, Temperature, 20 h. ^b Isolated yield in brackets. E. Variation of aldehyde addition and solvent mixtures ^{e e} Reaction conditions: 5a (0.144 mmol), 6a, NH4OAc (0.720 mmol), Solvent, Temperature, 20 h. ^b Isolated yield Example 8. Reaction condition optimization Reactions of enol 5a, NH4OAc, and 4-pyridinecarboxaldehyde (6a) under various conditions were investigated (Table 1). When heated together in EtOH at 70 °C overnight, the starting material was consumed and 37% of the desired product 7a was detected by HPLC analysis (entry 1). Enamine 8 was identified as a major side-product (27%). To investigate whether this enamine is productive, 8 was independently synthesized and subjected to the reaction conditions with no conversion to 7a observed. ¹¹ While not wishing to be bound by theory, it is believed that the reaction mechanism proceeds through initial condensation of ammonia with the aldehyde. Utilization of 1,4-dioxane resulted in increased conversion to the desired product 7a (60%) and reduction of enamine 8 (4%); however, when the reaction was performed in toluene 74% of the starting material was left unconsumed (entries 2 and 3). Other ethereal solvents, such as THF, CPME, and TBME were also productive. ¹¹ Increasing the equivalents of aldehyde from 1.0 to 1.5 was beneficial (entry 4) and gave 70% of pyrrole 7a (isolated in 58% yield); however, increasing the equivalents further provided no apparentl advantage (entry 5).. Use of (NH4)2CO3 resulted in a significant reduction in conversion, whereas NH4Cl provided no detectable levels of product (entries 6 and 7). ¹ The reaction was relatively insensitive to the equivalents of NH4OAc but adding >5 equivalents did not appear to be beneficial (entries 8 and 9).. Conducting the reaction at 90 °C resulted in complete conversion of the starting material and 64% of pyrrole 7a was detected (entry 11), whereas decreasing the temperature to 50 °C led to a significant reduction in product formation (entry 11). It was still observed that when the reaction was performed in toluene (entry 3), formation of enamine 8 was also suppressed. In a mixed solvent system 69% of the product 7a was observed (entry 12), matching the conversion observed in 1,4-dioxane. Additionally, full consumption of the starting material was observed and formation of enamine 8 was minimized. Table 1. ^a

a5a (0.144 mmol), 6a, NH ₃ source, Solvent (20 vol), T °C, 20 h. ^b Isolated yield in brackets. ^c 6a was added as a solution in 1,4-dioxane (10 vol) over 2.5 h to 5a and NH ₄ OAc in Solvent (10 vol). Example 9. Synthesis of Compounds 9 and 10 tert-Butyl 5-oxo-2-phenyl-4-(phenylamino)-7,8-dihydro-2H-pyrido[4,3-d][ 1,3]thiazine- 6(5H)-carboxylate, 9 A stirred solution of 5a (500 mg, 1.44 mmol, 1.00 equiv), benzaldehyde (220 µL, 2.15 mmol, 1.50 eq), and NH4OAc (553 mg, 7.18 mmol, 5.00 eq) in 1,4-dioxane (10.0 mL) was heated to 70 °C overnight. The reaction mixture was diluted with water (50 mL) and filtered. The precipitate was purified by silica gel chromatography using a 40 g SiO2 cartridge and a linear gradient of 0-50% EtOAc in heptane over 18 CV, to afford 9 (140 mg, 19%, 85% purity) as a yellow solid. 1H NMR (400 MHz, Chloroform-d) δ 13.33 (s, 1H), 7.49 – 7.42 (m, 2H), 7.28 (dd, J = 8.2, 6.5 Hz, 4H), 7.25 – 7.16 (m, 2H), 7.15 – 7.05 (m, 2H), 5.55 (d, J = 1.8 Hz, 1H), 3.97 (dt, J = 12.9, 5.3 Hz, 1H), 3.62 (ddd, J = 12.9, 10.9, 3.8 Hz, 1H), 2.85 (dddd, J = 15.9, 11.0, 4.9, 1.9 Hz, 1H), 2.73 (ddd, J = 15.0, 5.7, 3.8 Hz, 1H), 1.50 (s, 9H); 1 ³ C NMR (101 MHz, Chloroform-d) δ 167.8, 166.8, 165.4, 152.0, 138.9, 136.8, 129.0, 128.8, 128.8, 127.9, 127.5, 125.4, 94.8, 83.1, 64.1, 42.8, 33.7, 28.1; HRMS (ESI) calculated for C21H25N3O3S ⁺ [M+H] ⁺ 436.1695; found m/z 436.1697. Example 10. Conversion of 9 to Pyrrole 7ac Example 11. Synthesis of tert-Butyl 4-hydroxy-6-oxo-5-(phenylcarbamothioyl)-3,6- dihydropyridine-1(2H)-carboxylate, 5a ¹ Synthesised according to GP1 using tert-butyl 2,4-dioxopiperidine-1-carboxylate (2.00 g, 9.38 mmol) and isothiocyanatobenzene (1.12 mL, 9.38 mmol). Purified by silica gel chromatography using a 40 g SiO2 cartridge and a linear gradient of 0-50% EtOAc in heptane over 15 CV to give 5a (3.13 g, 96%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 15.31 (s, 1H), 12.84 (s, 1H), 7.57 (d, J = 7.9 Hz, 2H), 7.44 (t, J = 7.7 Hz, 2H), 7.31 (t, J = 7.4 Hz, 1H), 3.77 (t, J = 6.5 Hz, 2H), 2.81 (t, J = 6.4 Hz, 2H), 1.47 (s, 9H); 1 ³ C NMR (400 MHz, DMSO-d6) δ 189.5, 181.7, 166.1, 152.4, 138.4, 129.3, 127.4, 125.2, 105.7, 82.8, 41.0, 30.8, 28.1; HRMS (ESI) calculated for C17H21N2O4S ⁺ [M+H] ⁺ 349.1222; found m/z 349.1223. The ¹ H NMR data matched that of the literature. ¹ Example 12. Synthesis of tert-Butyl 4-amino-6-oxo-5-(phenylcarbamothioyl)-3,6- dihydropyridine-1(2H)-carboxylate, 8 A mixture of 5a (1.00 g, 2.87 mmol, 1.00 eq) and NH4OAc (2.21 g, 28.7 mmol, 10.0 eq) in EtOH (12 mL) was heated to 70 °C overnight. The reaction mixture was concentrated to ~4 mL and then quenched with saturated aqueous NaHCO3. The mixture was extracted with DCM (3 × 20 mL) and the combined organic extracts were dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography, using a 40 g SiO2 cartridge and a linear gradient of 5-100% EtOAc in heptane over 15 CV, to afford 8 (576 mg, 58%) as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 13.18 (s, 1H), 11.30 (s, 1H), 8.74 (s, 1H), 7.51 (d, J = 7.9 Hz, 2H), 7.38 (t, J = 7.8 Hz, 2H), 7.22 (t, J = 7.4 Hz, 1H), 3.67 (t, J = 6.3 Hz, 2H), 2.76 (t, J = 6.2 Hz, 2H), 1.46 (s, 9H); 1 ³ C NMR (101 MHz, DMSO-d6) δ 190.8, 168.0, 166.8, 152.8, 139.7, 128.9, 126., 125.6, 98.7, 82.1, 41.0, 31.3, 28.2; HRMS (ESI) calculated for C17H20N3O3S ^– [M-H] ^– 346.1225; found m/z 346.1227. Example 13. Synthesis of tert-Butyl 5-((2-chlorophenyl)carbamothioyl)-4-hydroxy-6- oxo-3,6-dihydropyridine-1(2H)-carboxylate, 5r Synthesised according to GP1 using tert-butyl 2,4-dioxopiperidine-1-carboxylate (300 mg, 1.41 mmol) and 1-chloro-2-isothiocyanatobenzene (239 mg, 1.41 mmol). Purified by silica gel chromatography using a 40 g SiO2 cartridge and a linear gradient of 0-25% EtOAc in heptane over 15 CV to give 5r (379 mg, 70%) as a white solid. 1H NMR (400 MHz, Chloroform-d) δ 13.50 (s, 1H), 7.53 (d, J = 7.7 Hz, 1H), 7.49 (d, J = 7.7 Hz, 1H), 7.35 – 7.27 (m, 2H), 3.87 (t, J = 6.6 Hz, 2H), 2.83 (t, J = 6.6 Hz, 2H), 1.56 (s, 9H); 1 ³ C NMR (101 MHz, Chloroform-d) δ 191.1, 186.7, 167.9, 152.4, 135.6, 131.3, 130.6, 129.3, 129.3, 127.5, 102.5, 84.3, 40.8, 32.2, 28.5; HRMS (ESI) calculated for C17H19ClN2O3SNa ⁺ [M+Na] ⁺ 405.0652; found m/z 405.0651. Example 14. Synthesis of tert-Butyl 5-((3-chlorophenyl)carbamothioyl)-4-hydroxy-6- oxo-3,6-dihydropyridine-1(2H)-carboxylate, 5s Synthesised according to GP1 using tert-butyl 2,4-dioxopiperidine-1-carboxylate (300 mg, 1.41 mmol) and 1-chloro-3-isothiocyanatobenzene (239 mg, 1.41 mmol). Purified by silica gel chromatography using a 40 g SiO2 cartridge and a linear gradient of 0-30% EtOAc in heptane over 15 CV to give 5s (360 mg, 67%) as an off-white solid. 1H NMR (400 MHz, Chloroform-d) δ 13.57 (s, 1H), 7.43 (s, 1H), 7.32 – 7.24 (m, 1H), 7.22 – 7.19 (m, 2H), 3.78 (t, J = 6.6 Hz, 2H), 2.75 (t, J = 6.6 Hz, 2H), 1.49 (s, 9H); 1 ³ C NMR (101 MHz, Chloroform-d) δ 189.7, 186.4, 167.8, 152.0, 138.8, 134.6, 130.0, 127.6, 126.1, 124.1, 102.1, 84.1, 40.5, 31.9, 28.2. HRMS (ESI) calculated for C17H20ClN2O3S ⁺ [M+H] ⁺ 383.0832; found m/z 383.0829. Example 15. Synthesis of tert-Butyl 5-((4-chlorophenyl)carbamothioyl)-4-hydroxy-6- oxo-3,6-dihydropyridine-1(2H)-carboxylate, 5t Synthesised according to GP1 using tert-butyl 2,4-dioxopiperidine-1-carboxylate (300 mg, 1.41 mmol) and 1-chloro-4-isothiocyanatobenzene (239 mg, 1.41 mmol). Purified by silica gel chromatography using a 40 g SiO2 cartridge and a linear gradient of 0-35% EtOAc in heptane over 15 CV to give 5t (343 mg, 64%) as a white solid. 1H NMR (400 MHz, Chloroform-d) δ 13.60 (s, 1H), 7.38 (s, 4H), 3.85 (t, J = 6.6 Hz, 2H), 2.81 (t, J = 6.6 Hz, 2H), 1.56 (s, 9H); ¹³ C NMR (101 MHz, Chloroform-d) δ 189.9, 186.6, 168.1, 152.2, 136.5, 133.3, 129.6, 127.6, 102.4, 84.4, 40.8, 32.2, 28.5; HRMS (ESI) calculated for C17H20ClN2O3S ⁺ [M+H] ⁺ 383.0832; found m/z 383.0826. Example 16. Synthesis of tert-Butyl 4-hydroxy-5-((2-methoxyphenyl)carbamothioyl)- 6-oxo-3,6-dihydropyridine-1(2H)-carboxylate, 5u ² Synthesised according to GP1 using tert-butyl 2,4-dioxopiperidine-1-carboxylate (300 mg, 1.41 mmol) and 1-isothiocyanato-2-methoxybenzene (190 µL, 1.41 mmol). Purified by silica gel chromatography using a 40 g SiO2 cartridge and a linear gradient of 0-35% EtOAc in heptane over 15 CV to give 5u (396 mg, 74%) as a white solid. 1H NMR (400 MHz, Chloroform-d) δ 13.33 (s, 1H), 7.66 (d, 1H), 7.18 (t, J = 7.8, 1.6 Hz, 1H), 6.91 – 6.86 (m, 2H), 3.78 – 3.71 (m, 5H), 2.69 (t, J = 6.6 Hz, 2H), 1.47 (s, 9H); 1 ³ C NMR (101 MHz, Chloroform-d) δ 188.9, 185.7, 167.5, 153.4, 152.2, 128.5, 127.0, 126.6, 120.2, 111.6, 102.4, 83.7, 56.1, 40.5, 31.9, 28.3; HRMS (ESI) calculated for C18H21N2O5S ^– [M-H] ^– 377.1171; found m/z 377.1169. Example 17. Synthesis of tert-Butyl 5-((4-(ethoxycarbonyl)phenyl)carbamothioyl)-4- hydroxy-6-oxo-3,6-dihydropyridine-1(2H)-carboxylate, 5v Synthesised according to GP1 using tert-butyl 2,4-dioxopiperidine-1-carboxylate (300 mg, 1.41 mmol) and ethyl 4-isothiocyanatobenzoate (292 mg, 1.41 mmol). Purified by silica gel chromatography using a 40 g SiO2 cartridge and a linear gradient of 0-45% EtOAc in heptane over 14 CV to give 5v (319 mg, 54%) as a white solid. 1H NMR (400 MHz, Chloroform-d) δ 13.81 (s, 1H), 8.09 (d, 2H), 7.59 (d, 2H), 4.38 (q, J = 7.1 Hz, 2H), 3.85 (t, J = 6.6 Hz, 2H), 2.83 (t, J = 6.6 Hz, 2H), 1.56 (s, 9H), 1.39 (t, J = 7.1 Hz, 3H); 1 ³ C NMR (101 MHz, Chloroform-d) δ 189.8, 186.8, 168.1, 166.3, 152.2, 142.0, 130.8, 129.4, 125.7, 102.6, 84.5, 61.5, 40.8, 32.2, 28.5, 14.8; HRMS (ESI) calculated for C20H25N2O6S ⁺ [M+H] ⁺ 421.1433; found m/z 421.1429. Example 18. Synthesis of tert-Butyl 4-hydroxy-3-methyl-6-oxo-5- (phenylcarbamothioyl)-3,6-dihydropyridine-1(2H)-carboxylate, 5y Synthesised according to GP1 using tert-butyl 5-methyl-2,4-dioxopiperidine-1- carboxylate (500 mg, 2.20 mmol) and isothiocyanatobenzene (263 µL, 2.20 mmol). Purified by silica gel chromatography using a 40 g SiO2 cartridge and a linear gradient of 0-40% EtOAc in heptane over 15 CV to give 5y (585 mg, 73%) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ 13.61 (s, 1H), 7.42 (d, J = 4.3 Hz, 4H), 7.35 – 7.27 (m, 1H), 3.86 (dd, J = 13.0, 4.6 Hz, 1H), 3.63 (dd, J = 13.0, 7.1 Hz, 1H), 2.86 (td, J = 7.1, 4.8 Hz, 1H), 1.56 (s, 9H), 1.34 (d, J = 7.0 Hz, 3H); 1 ³ C NMR (101 MHz, CDCl3) δ 189.7, 189.3, 167.5, 152.1, 137.6, 129.0, 127.4, 125.9, 100.9, 83.8, 46.6, 35.9, 28.1, 14.4; HRMS (ESI) calculated for C18H23N2O4S ⁺ [M+H] ⁺ 363.1378; found m/z 363.1379.

Example 19. Synthesis of Sodium hydroxy(pyridin-4-yl)methanesulfonate, 11 To a solution of 4-formylpyridine (600 uL, 6.37 mmol, 1.00 eq) in EtOH (12.7 mL) was added aq. 3 m NaHSO3 (2.14 mL, 6.43 mmol, 1.01 eq) and the mixture stirred at room temperature for 3 hours. Toluene (10 mL) was added to the reaction mixture for azeotropic removal of water, and the solvent was evaporated to dryness. Additional toluene (10 mL) was added and the solvent was evaporated again to dryness to afford sodium hydroxy(pyridin-4-yl)methanesulfonate 11 (1.10 g, 82%) as a white solid which was used without further purification. 1H NMR (400 MHz, DMSO-d6) δ 8.55 – 8.34 (m, 2H), 7.52 – 7.25 (m, 2H), 6.25 (s, 1H), 5.01 (s, 1H). Example 20. Synthesis of tert-Butyl 4-oxo-3-(phenylamino)-2-(pyridin-4-yl)-1,4,6,7- tetrahydro-5H-pyrrolo[3,2-c]pyridine-5-carboxylate, 7a Small-scale: Synthesised according to GP2 using 5a (100 mg, 0.287 mmol) and isonicotinaldehyde (40.6 µL, 0.431 mmol). Purified by silica gel chromatography using a 24 g SiO2 cartridge and a linear gradient of 20-100% EtOAc in heptane over 10 CV, followed by a linear gradient of 0-10% MeOH in DCM over 20 CV to give 7a (81 mg, 70%) as an off-white solid. 1g scale: The reaction was carried out according to GP2 using 5a (1.00 g, 2.87 mmol) and isonicotinaldehyde (406 µL, 4.31 mmol) to give 7a (739 mg, 64%) as an off-white solid. 1H NMR (400 MHz, Chloroform-d) 11.25 (s, 1H), 8.34 – 8.24 (m, 2H), 7.39 – 7.28 (m, 2H), 7.23 (s, 1H), 7.12 – 6.99 (m, 2H), 6.75 (tt, J = 7.4, 1.1 Hz, 1H), 6.70 – 6.58 (m, 2H), 4.04 (t, J = 6.3 Hz, 2H), 2.85 (t, J = 6.3 Hz, 2H), 1.52 (s, 9H). ¹³ C NMR (101 MHz, Chloroform-d) δ 164.0, 152.8, 148.9, 143.3, 139.3, 138.8, 129.2, 128.8, 120.1, 119.0, 118.6, 116.1, 108.8, 83.0, 45.3, 28.2, 22.8. HRMS (ESI) calculated for C23H25N4O3 ⁺ [M+H] ⁺ 405.1927; found m/z 405.1929. Example 21. Synthesis of tert-Butyl-4-oxo-3-(phenylamino)-2-(pyridin-2-yl)-1,4,6,7- tetrahydro-5H-pyrrolo[3,2-c]pyridine-5-carboxylate, 7b Synthesised according to GP2 using tert-butyl 5a (100 mg, 0.287 mmol) and 3- bromoisonicotinaldehyde (80.1 mg, 0.431 mmol). Purified by silica gel chromatography using a 24 g SiO2 cartridge and a linear gradient of 20-100% EtOAc in heptane over 10 CV, followed by a linear gradient of 0-10% MeOH in DCM over 20 CV to give 7b (75 mg, 54%) as a yellow solid. 1H NMR (400 MHz, Chloroform-d) δ 9.29 (s, 1H), 8.60 (s, 1H), 8.08 (d, J = 5.1 Hz, 1H), 7.18 (d, J = 5.1 Hz, 1H), 6.98 (t, J = 7.7 Hz, 2H), 6.69 (t, J = 7.3 Hz, 1H), 6.61 (d, J = 8.0 Hz, 2H), 4.12 (t, J = 6.2 Hz, 2H), 2.96 (t, J = 6.3 Hz, 2H), 1.55 (s, 9H); 1 ³ C NMR (101 MHz, Chloroform-d) δ 164.0, 152.9, 152.2, 147.5, 142.0, 139.4, 137.3, 130.4, 128.6, 124.1, 120.5, 116.7, 112.9, 107.1, 83.0, 45.1, 28.2, 23.1; HRMS (ESI) calculated for C23H24BrN4O3 ⁺ [M+H] ⁺ 485.1014; found m/z 485.1012. Example 22.Syntheis of tert-Butyl 2-(3-methylpyridin-4-yl)-4-oxo-3-(phenylamino)- 1,4,6,7-tetrahydro-5H-pyrrolo[3,2-c]pyridine-5-carboxylate, 7c Synthesised according to GP2 using 5a (100 mg, 0.287 mmol) and 3- methylisonicotinaldehyde (52.2 mg, 0.431 mmol). Purified by silica gel chromatography using a 24 g SiO2 cartridge and a linear gradient of 20-100% EtOAc in heptane over 10 CV, followed by a linear gradient of 0-10% MeOH in DCM over 20 CV to give 7c (50 mg, 42%) as a yellow solid. 1H NMR (400 MHz, Chloroform-d) δ 9.31 (s, 1H), 8.11 (s, 2H), 7.40 (s, 1H), 7.10 (d, J = 5.2 Hz, 1H), 6.83 (t, J = 7.7 Hz, 2H), 6.56 (t, J = 7.3 Hz, 1H), 6.45 (d, J = 8.0 Hz, 2H), 4.04 (t, J = 6.3 Hz, 2H), 2.86 (t, J = 6.3 Hz, 2H), 2.10 (s, 3H), 1.49 (s, 9H); 1 ³ C NMR (101 MHz, Chloroform-d) δ 164.2, 153.1, 150.5, 145.9, 142.9, 141.2, 137.3, 131.5, 128.4, 128.4, 122.0, 119.8, 116.0, 115.1, 107.6, 82.69, 45.2, 28.2, 23.0, 17.4. HRMS (ESI) calculated for C24H27rN4O3 ⁺ [M+H] ⁺ 419.2083; found m/z 419.2083. Example 23. Synthesis of tert-Butyl-2-(2-bromopyridin-4-yl)-4-oxo-3-(phenylamino)- 1,4,6,7-tetrahydro-5H-pyrrolo[3,2-c]pyridine-5-carboxylate, 7d Synthesised according to GP2 using 5a (100 mg, 0.287 mmol) and 2- bromoisonicotinaldehyde (80.1 mg, 0.431 mmol). Purified by silica gel chromatography using a 24 g SiO2 cartridge and a linear gradient of 20-100% EtOAc in heptane over 10 CV, followed by a linear gradient of 0-10% MeOH in DCM over 20 CV to give 7d (56 mg, 40%) as a yellow solid. 1H NMR (400 MHz, Chloroform-d) δ 9.52 (s, 1H), 8.01 (d, J = 5.4 Hz, 1H), 7.36 (s, 1H), 7.15 – 7.03 (m, 3H), 6.79 (t, J = 7.2 Hz, 1H), 6.62 (d, J = 7.9 Hz, 2H), 4.11 (t, J = 6.4 Hz, 2H), 2.95 (d, J = 6.4 Hz, 2H), 1.53 (s, 9 H); 1 ³ C NMR (101 MHz, Chloroform-d) δ 164.0, 152.7, 150.3, 149.5, 142.5, 142.1, 140.9, 139.0, 130.2, 129.0, 121.8, 120.7, 118.1, 116.6, 116.4, 108.9, 83.4, 45.2, 28.1, 22.9; HRMS (ESI) calculated for C23H24BrN4O3 ⁺ [M+H] ⁺ 483.1032; found m/z 483.1028. Example 24. Synthesis of tert-Butyl-2-(2-methoxypyridin-4-yl)-4-oxo-3- (phenylamino)-1,4,6,7-tetrahydro-5H-pyrrolo[3,2-c]pyridine-5 -carboxylate, 7e Synthesised according to GP2 using 5a (100 mg, 0.287 mmol) and 2- methoxyisonicotinaldehyde (40.9 µL, 0.431 mmol). Purified by silica gel chromatography using a 24 g SiO2 cartridge and a linear gradient of 20-100% EtOAc in heptane over 10 CV, followed by a linear gradient of 0-10% MeOH in DCM over 20 CV to give 7e (100 mg, 80%) as an off-white solid. 1H NMR (400 MHz, Chloroform-d) δ 10.00 (s, 1H), 7.90 (d, J = 5.6 Hz, 1H), 7.10 – 7.01 (m, 3H), 6.95 (d, J = 5.6 Hz, 1H), 6.77 – 6.69 (m, 2H), 6.62 (d, J = 8.0 Hz, 2H), 4.03 (t, J = 6.3 Hz, 2H), 2.85 (t, J = 6.3 Hz, 2H), 1.51 (s, 9H); 1 ³ C NMR (101 MHz, Chloroform-d) δ 164.6, 164.1, 152.8, 146.7, 143.5, 141.3, 138.2, 128.8, 128.4, 119.9, 119.0, 115.9, 112.87, 108.9, 104.2, 83.0, 53.6, 45.3, 28.1, 22.8; HRMS (ESI) calculated for C24H27N4O4 ⁺ [M+H] ⁺ 435.2032; found m/z 435.2035. Example 25. Synthesis of tert-Butyl-2-(2-fluoropyridin-4-yl)-4-oxo-3-(phenylamino)- 1,4,6,7-tetrahydro-5H-pyrrolo[3,2-c]pyridine-5-carboxylate, 7f Synthesised according to GP2 using 5a (100 mg, 0.287 mmol) and 2- fluoroisonicotinaldehyde (53.9 mg, 0.431 mmol). Purified by silica gel chromatography using a 24 g SiO2 cartridge and a linear gradient of 20-100% EtOAc in heptane over 10 CV, followed by a linear gradient of 0-10% MeOH in DCM over 20 CV to give 7f (72 mg, 59%) as a yellow solid. ¹ H NMR (400 MHz, Chloroform-d) δ 10.02 (s, 1H), 7.89 (d, J = 5.5 Hz, 1H), 7.21 – 7.11 (m, 2H), 7.07 (t, J = 7.7 Hz, 2H), 6.88 (d, J = 1.4 Hz, 1H), 6.77 (t, J = 7.3 Hz, 1H), 6.63 (d, J = 7.9 Hz, 2H), 4.06 (t, J = 6.3 Hz, 2H), 2.90 (t, J = 6.3 Hz, 2H), 1.52 (s, 9H); ¹³ C NMR (101 MHz, Chloroform-d) δ 164.2, 152.8, 147.1 (d, J = 15.1 Hz), 143.8 (d, J = 9.2 Hz), 143.0, 139.15, 130.0, 129.1, 120.6, 117.9, 116.9, 116.3, 109.0, 103.5 (d, J = 39.2 Hz), 83.4, 45.4, 28.2, 22.8; ¹⁹ F NMR (376 MHz, Chloroform-d) δ –69.1; HRMS (ESI) calculated for C23H24FN4O3 ⁺ [M+H] ⁺ 423.1833; found m/z 428.1830. Example 26. Synthesis of tert-Butyl 4-oxo-3-(phenylamino)-2-(pyridin-2-yl)-1,4,6,7- tetrahydro-5H-pyrrolo[3,2-c]pyridine-5-carboxylate, 7g Synthesised according to GP2 using 5a (100 mg, 0.287 mmol) and picolinaldehyde (40.9 µL, 0.431 mmol). Purified by silica gel chromatography using a 24 g SiO ² cartridge and a linear gradient of 20-100% EtOAc in heptane over 10 CV, followed by a linear gradient of 0-10% MeOH in DCM over 20 CV to give 7g (57 mg, 49%) as an off-white solid. ¹ H NMR (400 MHz, Chloroform-d) δ 10.01 (br s, 1H), 8.43 (d, J = 5.0 Hz, 1H), 7.46 (td, J = 7.7, 1.8 Hz, 1H), 7.23 (s, 1H), 7.18 (d, J = 8.2 Hz, 1H), 7.11 (t, J = 8.5, 7.2 Hz, 2H), 6.99 (ddd, J = 7.6, 4.9, 1.1 Hz, 1H), 6.78 (t, J = 7.3 Hz, 1H), 6.73 (d, J = 7.6 Hz, 2H), 4.10 (t, J = 6.3 Hz, 2H), 2.91 (t, J = 6.3 Hz, 2H), 1.55 (s, 9H); ¹³ C NMR (101 MHz, Chloroform-d 3) δ 163.8, 153.0, 148.6, 148.0, 143.9, 136.1, 136.7, 128.9, 127.3, 121.8, 121.0, 120.4, 119.8, 116.0, 109.3, 82.7, 45.2, 28.2, 22.9; HRMS (ESI) calculated for C23H25N4O3 ⁺ [M+H] ⁺ 405.1927; found m/z 405.1928. Example 27. Synthesis of tert-Butyl-2-(5-bromopyridin-2-yl)-4-oxo-3-(phenylamino)- 1,4,6,7-tetrahydro-5H-pyrrolo[3,2-c]pyridine-5-carboxylate, 7h Synthesised according to GP2 using 5a (100 mg, 0.287 mmol) and 5- bromopicolinaldehyde (40.9 µL, 0.431 mmol). Purified by silica gel chromatography using a 24 g SiO2 cartridge and a linear gradient of 20-100% EtOAc in heptane over 10 CV, followed by a linear gradient of 0-10% MeOH in DCM over 20 CV to give 7h (72 mg, 52%) as a yellow solid. ¹ H NMR (400 MHz, Chloroform-d) δ 9.59 (s, 1H), 8.48 (d, J = 2.3 Hz, 1H), 7.54 (dd, J = 8.6, 2.4 Hz, 1H), 7.18 – 7.08 (m, 2H), 7.00 (d, J = 8.6 Hz, 1H), 6.85 – 6.76 (m, 1H), 6.75 – 6.68 (m, 2H), 4.11 (t, J = 6.3 Hz, 2H), 2.94 (t, J = 6.3 Hz, 2H), 1.56 (s, 9H); ¹³ C NMR (101 MHz, Chloroform-d) δ 163.7, 153.0, 149.0, 146.8, 143.5, 139.0, 137.0, 129.0, 127.9, 121.9, 120.9, 120.1, 116.4, 116.0, 109.4, 82.9, 45.1, 28.2, 22.9; HRMS (ESI) calculated for C23H24BrN4O3 ⁺ [M+H] ⁺ 483.1032; found m/z 483.1026. Example 28. Synthesis of tert-Butyl 2-(5-methylpyridin-2-yl)-4-oxo-3-(phenylamino)- 1,4,6,7-tetrahydro-5H-pyrrolo[3,2-c]pyridine-5-carboxylate, 7i Synthesised according to GP2 using 5a (100 mg, 0.287 mmol) and 5- methylpicolinaldehyde (52.2 µL, 0.431 mmol). Purified by silica gel chromatography using a 24 g SiO2 cartridge and a linear gradient of 20-100% EtOAc in heptane over 10 CV, followed by a linear gradient of 0-10% MeOH in DCM over 20 CV to give 7i (76 mg, 63%) as an off-white solid. ¹ H NMR (400 MHz, Chloroform-d) δ 10.60 (s, 1H), 8.36 (d, J = 2.2 Hz, 1H), 7.42 – 7.35 (m, 1H), 7.30 – 7.15 (m, 3H), 6.85 (dd, J = 20.3, 7.6 Hz, 3H), 4.17 (t, J = 6.3 Hz, 2H), 2.92 (t, J = 6.3 Hz, 2H), 2.35 (s, 3H), 1.64 (s, 9H); ¹³ C NMR (101 MHz, Chloroform-d) δ 163.9, 153.1, 148.1, 146.3, 144.2, 137.4, 136.6, 130.0, 128.8, 126.6, 122.2, 120.6, 119.62, 115.9, 109.3, 82.7, 45.2, 28.2, 22.8, 18.2; HRMS (ESI) calculated for C24H27N4O3 ⁺ [M+H] ⁺ 419.2083; found m/z 419.2086. Example 29. Synthesis of tert-Butyl 4-oxo-3-(phenylamino)-2-(quinolin-2-yl)-1,4,6,7- tetrahydro-5H-pyrrolo[3,2-c]pyridine-5-carboxylate, 7j Synthesised according to GP2 using 5a (100 mg, 0.287 mmol) and quinoline-2- carbaldehyde (67.6 mg, 0.431 mmol). Purified by silica gel chromatography using a 24 g SiO2 cartridge and a linear gradient of 20-100% EtOAc in heptane over 10 CV, followed by a linear gradient of 0-10% MeOH in DCM over 20 CV to give 7j (70 mg, 53%) as an orange solid. ¹ H NMR (400 MHz, Chloroform-d 3) δ 7.96 (d, J = 8.5 Hz, 1H), 7.90 (d, J = 8.8 Hz, 1H), 7.73 – 7.61 (m, 2H), 7.48 (d, J = 8.7 Hz, 1H), 7.43 (t, J = 7.5 Hz, 1H), 7.34 (s, 1H), 7.13 – 7.05 (m, 2H), 6.85 – 6.74 (m, 3H), 4.09 (t, J = 6.3 Hz, 2H), 2.84 (t, J = 6.3 Hz, 2H), 1.55 (s, 9H); ¹³ C NMR (101 MHz, Chloroform-d) δ 163.2, 152.4, 143.9, 137.5, 135.8, 129.2, 128.3, 127.4, 127.1, 126.0, 124.9, 119.4, 119.0, 115.4, 108.8, 82.1, 44.5, 27.6, 22.2; HRMS (ESI) calculated for C27H27N4O3 ⁺ [M+H] ⁺ 455.2083; found m/z 455.2086.

Example 30. Synthesis of tert-Butyl 4-oxo-3-(phenylamino)-2-(pyridin-3-yl)-1,4,6,7- tetrahydro-5H-pyrrolo[3,2-c]pyridine-5-carboxylate, 7k Synthesised according to GP2 using 5a (100 mg, 0.287 mmol) and 3-formylpyridine (40.4 µL, 0.431 mmol). Purified by silica gel chromatography using a 24 g SiO2 cartridge and a linear gradient of 20-100% EtOAc in heptane over 10 CV, followed by a linear gradient of 0-10% MeOH in DCM over 20 CV to give 7k (22 mg, 19% yield) as a yellow solid. ¹ H NMR (400 MHz, Chloroform-d) δ 11.23 (s, 1H), 9.00 (s, 1H), 8.20 (d, J = 4.9 Hz, 1H), 7.79 (dd, J = 8.1, 2.0 Hz, 1H), 7.19 – 6.97 (m, 4H), 6.71 (t, J = 7.3 Hz, 1H), 6.62 (d, J = 7.9 Hz, 2H), 4.03 (t, J = 6.3 Hz, 2H), 2.88 (t, J = 6.3 Hz, 2H), 1.53 (s, 9H). ¹³ C NMR (101 MHz, Chloroform-d) δ 164.0, 152.92, 143.7, 143.4, 138.4, 134.1, 129.2, 128.9, 127.5, 124.1, 119.8, 117.5, 115.9, 108.6, 82.8, 45.4, 28.2, 22.7. HRMS (ESI) calculated for C23H25N4O3 ⁺ [M+H] ⁺ 405.1927; found m/z 405.1927. Example 31. Synthesis of tert-Butyl 4-oxo-3-(phenylamino)-2-(thiazol-2-yl)-1,4,6,7- tetrahydro-5H-pyrrolo[3,2-c]pyridine-5-carboxylate, 7l Synthesised according to GP2 using 5a (100 mg, 0.287 mmol) and thiazole-2-carbaldehyde (37.8 µL, 0.431 mmol). Purified by silica gel chromatography using a 24 g SiO2 cartridge and a linear gradient of 20-100% EtOAc in heptane over 10 CV, followed by a linear gradient of 0-10% MeOH in DCM over 20 CV to give 7l (40 mg, 34%) as a yellow solid. ¹ H NMR (400 MHz, Chloroform-d) δ 10.57 (s, 1H), 7.64 (d, J = 3.3 Hz, 1H), 7.21 – 7.12 (m, 3H), 7.10 (s, 1H), 6.86 (t, J = 7.3 Hz, 1H), 6.79 (d, J = 8.0 Hz, 2H), 4.10 (t, J = 6.3 Hz, 2H), 2.91 (t, J = 6.3 Hz, 2H), 1.55 (s, 9H); ¹³ C NMR (101 MHz, Chloroform-d 3) δ 163.2, 157.0, 153.0, 143.0, 139.1, 138.7, 129.0, 120.8, 118.4, 118.2, 116.9, 109.2, 83.0, 45.0, 28.2, 22.9; HRMS (ESI) calculated for C21H22N4O3SNa ⁺ [M+Na] ⁺ 433.1310; found m/z 433.1308. Example 32. Synthesis of tert-Butyl 2-(1-methyl-1H-imidazol-2-yl)-4-oxo-3- (phenylamino)-1,4,6,7-tetrahydro-5H-pyrrolo[3,2-c]pyridine-5 -carboxylate, 7m Synthesised according to GP2 using 5a (100 mg, 0.287 mmol) and 1-methyl-1H- imidazole-2-carbaldehyde (47.4 mg, 0.431 mmol). Purified by silica gel chromatography using a 24 g SiO2 cartridge and a linear gradient of 20-100% EtOAc in heptane over 10 CV, followed by a linear gradient of 0-10% MeOH in DCM over 20 CV to give 7m (40 mg, 34%) as a yellow solid. ¹ H NMR (400 MHz, Chloroform-d) δ 12.75 (br s, 1H), 7.04 – 6.94 (m, 3H), 6.73 (t, J = 7.3 Hz, 1H), 6.69 – 6.63 (m, 3H), 4.10 (t, J = 6.3 Hz, 2H), 3.34 (s, 3H), 2.94 (t, J = 6.3 Hz, 2H), 1.56 (s, 9H); ¹³ C NMR (101 MHz, Chloroform-d) δ 164.5, 153.1, 143.3, 141.8, 138.1, 128.8, 128.6, 126.4, 121.0, 120.0, 115.2,106.8, 106.5, 82.7, 45.4, 33.6, 28.2, 22.6; HRMS (ESI) calculated for C22H26N5O3 ⁺ [M+H] ⁺ 408.2036; found m/z 408.2035. Example 33. Synthesis of tert-Butyl 4-oxo-3-(phenylamino)-2-(4- (trifluoromethyl)phenyl)-1,4,6,7-tetrahydro-5H-pyrrolo[3,2-c ]pyridine-5- carboxylate, 7n Synthesised according to GP2 using 5a (100 mg, 0.287 mmol) and 4- (trifluoromethyl)benzaldehyde (60.0 µL, 0.431 mmol). Purified by silica gel chromatography using a 24 g SiO2 cartridge and a linear gradient of 0-55% EtOAc in heptane over 13 CV to give 7n (93 mg, 69%) as a yellow solid. ¹ H NMR (400 MHz, DMSO-d6) δ 11.96 (s, 1H), 7.77 (d, J = 8.1 Hz, 2H), 7.64 (d, J = 8.1 Hz, 2H), 7.35 (s, 1H), 7.02 (t, J = 7.6 Hz, 1H), 6.63 – 6.55 (m, 3H), 3.96 (t, J = 6.0 Hz, 2H), 2.95 (t, J = 6.0 Hz, 2H), 1.44 (s, 9H); ¹³ C NMR (101 MHz, DMSO-d6) δ 161.7, 153.1, 146.1, 139.0, 135.3, 128.7, 125.4, 124.7, 124.6, 122.6, 117.6, 114.0, 109.4, 81.3, 45.1, 27.8, 22.3; ¹⁹ F NMR (376 MHz, DMSO-d6) δ -60.7; HRMS (ESI) calculated for C25H25F3N3O3 ⁺ [M+H] ⁺ 472.1848; found m/z 472.1845. Example 34. Synthesis of tert-Butyl 2-(4-nitrophenyl)-4-oxo-3-(phenylamino)-1,4,6,7- tetrahydro-5H-pyrrolo[3,2-c]pyridine-5-carboxylate, 7o Synthesised according to GP2 using 5a (100 mg, 0.287 mmol) and 4-nitrobenzaldehyde (65.1 mg, 0.431 mmol). Purified by silica gel chromatography using a 24 g SiO2 cartridge and a linear gradient of 0-90% EtOAc in heptane over 10 CV to give 7o (95 mg, 74%) as a red solid. ¹ H NMR (400 MHz, DMSO-d6) δ 12.10 (s, 1H), 8.14 (d, J = 8.6 Hz, 2H), 7.77 (d, J = 8.6 Hz, 2H), 7.51 (s, 1H), 7.04 (t, J = 7.6 Hz, 2H), 6.71 – 6.54 (m, 3H), 3.97 (t, J = 6.2 Hz, 2H), 2.98 (t, J = 6.3 Hz, 2H), 1.45 (s, 9H); ¹³ C NMR (101 MHz, DMSO-d6) δ 162.2, 153.5, 145.8, 144.6, 140.7, 138.2, 129.2, 127.2, 124.9, 124., 122.2, 118.6, 114.8, 109.84, 81.9, 45.5, 28.3, 22.8; HRMS (ESI) calculated for C24H25N4O5 ⁺ [M+H] ⁺ 449.1823; found m/z 449.1823. Example 35. Synthesis of tert-Butyl 2-(4-cyanophenyl)-4-oxo-3-(phenylamino)- 1,4,6,7-tetrahydro-5H-pyrrolo[3,2-c]pyridine-5-carboxylate, 7p Synthesised according to GP2 using 5a (100 mg, 0.287 mmol) and 4-formylbenzonitrile (56.5 mg, 0.431 mmol). Purified by silica gel chromatography using a 24 g SiO2 cartridge and a linear gradient of 10-100% EtOAc in heptane over 20 CV to give 7p (76 mg, 62%) as a yellow solid. ¹ H NMR (400 MHz, Chloroform-d) δ 9.83 (s, 1H), 7.49 (d, J = 8.7 Hz, 2H), 7.40 (d, J = 8.6 Hz, 2H), 7.06 – 6.95 (m, 3H), 6.78 – 6.67 (m, 1H), 6.67 – 6.50 (m, 2H), 4.03 (t, J = 6.3 Hz, 2H), 2.89 (t, J = 6.3 Hz, 2H), 1.50 (s, 9H); ¹³ C NMR (101 MHz, Chloroform-d) δ 164.3, 152.6, 143.4, 138.3, 135.8, 132.2, 128.8, 127.6, 124.8, 120.0, 119.8, 119.3, 115.8, 108.8, 108.0, 83.1, 45.4, 28.1, 22.8; HRMS (ESI) calculated for C25H23N4O3 ^– [M-H] ^– 427.1770; found m/z 427.1773. Example 36. Synthesis of tert-Butyl 2-(3,5-difluorophenyl)-4-oxo-3-(phenylamino)- 1,4,6,7-tetrahydro-5H-pyrrolo[3,2-c]pyridine-5-carboxylate, 7q Synthesised according to GP2 using 5a (100 mg, 0.287 mmol) and 3,5- difluorobenzaldehyde (40.0 µL, 0.431 mmol). Purified by silica gel chromatography using a 24 g SiO2 cartridge and a linear gradient of 0-55% EtOAc in heptane over 10 CV to give 7q (82 mg, 65%) as a yellow solid. ¹ H NMR (400 MHz, DMSO-d6) δ 11.90 (br s, 1H), 7.34 (s, 1H), 7.30 – 7.23 (m, 2H), 7.10 – 7.00 (m, 2H), 6.97 (t, J = 9.0 Hz, 1H), 6.65 – 6.56 (m, 3H), 3.95 (t, J = 6.2 Hz, 2H), 2.94 (t, J = 6.2 Hz, 2H), 1.44 (s, 9H); ¹³ C NMR (101 MHz, DMSO-d6) δ 164.3, 162.0, 146.4, 139.4, 134.8, 129.2, 125.2, 122.5, 118.2, 114.4, 110.0, 107.7, 107.4, 81.8, 45.5, 28.3, 22.7; ¹⁹ F NMR (376 MHz, DMSO-d6) δ -110.0; HRMS (ESI) calculated for C24H24F2N3O3 ⁺ [M+H] ⁺ 440.1786; found m/z 440.1786. Example 37. Synthesis of tert-Butyl 4-oxo-3-(phenylamino)-2-(pyridin-3-yl)-1,4,6,7- tetrahydro-5H-pyrrolo[3,2-c]pyridine-5-carboxylate, 7a Due to solubility issues with bisulfite adduct 11, the reaction was carried out in a one-pot manner with 1,4-dioxane as the solvent, rather than following GP2. A mixture of 5a (100 mg, 0.287 mmol), 11 (90.9 mg, 0.431 mmol), and NH4OAc (111 mg, 1.44 mmol) in 1,4-dioxane (2.00 mL) was heated to 70 °C for 18 hours. Additional 11 (90.9 mg, 0.431 mmol) was added and the mixture stirred at 70 °C for a further 24 hours. The reaction mixture was quenched with saturated aqueous NaHCO3 (10 mL) and extracted with EtOAc (3 × 10 mL). The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. Purification was carried out by silica gel chromatography, eluting with n-heptane/EtOAc (80:20 to 0:100) and then DCM/MeOH (100:0 to 90:10) to afford 7a (35 mg, 30% yield) as a white solid. ¹ H NMR (400 MHz, Chloroform-d) δ 10.20 (s, 1H), 8.37 – 8.27 (m, 2H), 7.32 – 7.22 (m, 3H), 7.11 – 7.00 (m, 2H), 6.76 (tt, J = 7.3, 1.1 Hz, 1H), 6.70 – 6.61 (m, 2H), 4.08 (t, J = 6.3 Hz, 2H), 2.91 (t, J = 6.3 Hz, 2H), 1.54 (s, 9H); LCMS (ESI) calculated for C23H25N4O3 ⁺ [M+H] ⁺ 405.2; found m/z 405.3. The NMR/MS spectra matched that obtained previously. Example 38. Synthesis of tert-Butyl 3-((2-chlorophenyl)amino)-4-oxo-2-(pyridin-4- yl)-1,4,6,7-tetrahydro-5H-pyrrolo[3,2-c]pyridine-5-carboxyla te, 7r Synthesised according to GP2 using 5b (50.0 mg, 0.131 mmol) and 6a (18.5 µL, 0.197 mmol). Purified by silica gel chromatography using a 12 g SiO ² cartridge and a linear gradient of 0-100% EtOAc in heptane over 45 CV to give 7r (39.0 mg, 68%) as a yellow solid. ¹ H NMR (400 MHz, Chloroform-d) δ 11.27 (s, 1H), 8.31 (d, J = 5.4 Hz, 2H), 7.33 (d, J = 5.4 Hz, 2H), 7.27 (d, J = 4.7 Hz, 3H), 6.84 (t, J = 7.7 Hz, 1H), 6.66 (t, J = 7.6 Hz, 1H), 6.41 (d, J = 8.1 Hz, 1H), 4.06 (t, J = 6.4 Hz, 2H), 2.90 (t, J = 6.3 Hz, 2H), 1.51 (s, 9H); ¹³ C NMR (101 MHz, Chloroform-d) δ 163.8, 152.2, 144.0, 141.9, 141.7, 139.4, 129.5, 127.2, 121.6, 120.6, 119.7, 119.2, 114.4, 109.0, 83.5, 45.3, 28.2, 27.9, 22.5; HRMS (ESI) calculated for C23H24ClN4O3 ⁺ [M+H] ⁺ 439.1541; found m/z 439.1541. Example 39. Synthesis of tert-Butyl 3-((3-chlorophenyl)amino)-4-oxo-2-(pyridin-4- yl)-1,4,6,7-tetrahydro-5H-pyrrolo[3,2-c]pyridine-5-carboxyla te, 7s Synthesised according to GP2 using 5s (50.0 mg, 0.131 mmol) and 6a (18.5 µL, 0.197 mmol). Purified by silica gel chromatography using a 12 g SiO2 cartridge and a linear gradient of 0-100% EtOAc in heptane over 45 CV to give 7s (35 mg, 61%) as a yellow solid. ¹ H NMR (400 MHz, Chloroform-d) δ 11.10 (s, 1H), 8.32 (d, J = 6.3 Hz, 2H), 7.34 (d, J = 6.3 Hz, 2H), 7.19 (s, 1H), 6.98 (t, J = 8.0 Hz, 1H), 6.71 (d, J = 7.9 Hz, 1H), 6.59 – 6.53 (m, 2H), 4.07 (t, J = 6.3 Hz, 2H), 2.91 (t, J = 6.3 Hz, 2H), 1.54 (s, 9H); ¹³ C NMR (101 MHz, Chloroform-d) δ 164.3, 153.2, 148.1, 145.2, 140.3, 140.2, 135.1, 130.4, 129.3, 120.5, 119.5, 116.2, 114.7, 109.6, 83.7, 45.7, 28.8, 28.6, 23.2; HRMS (ESI) calculated for C23H24ClN4O3 ⁺ [M+H] ⁺ 439.1541; found m/z 439.1533. Example 40. Synthesis of tert-Butyl 3-((4-chlorophenyl)amino)-4-oxo-2-(pyridin-4- yl)-1,4,6,7-tetrahydro-5H-pyrrolo[3,2-c]pyridine-5-carboxyla te, 7t Synthesised according to GP2 using 5t (50.0 mg, 0.131 mmol) and 6a (18.5 µL, 0.197 mmol). Purified by silica gel chromatography using a 12 g SiO2 cartridge and a linear gradient of 0-100% EtOAc in heptane over 10 CV, followed by a linear gradient of 0-10% MeOH in DCM over 20 CV to give 7t (35 mg, 61%) as a yellow solid. ¹ H NMR (400 MHz, Chloroform-d) δ 10.94 (s, 1H), 8.31 (d, J = 6.1 Hz, 2H), 7.28 (d, J = 6.1 Hz, 2H), 7.25 (s, 1H), 7.00 (d, J = 8.8 Hz, 2H), 6.57 (d, J = 8.8 Hz, 2H), 4.08 (t, J = 6.3 Hz, 2H), 2.91 (t, J = 6.3 Hz, 2H), 1.54 (s, 9H); ¹³ C NMR (101 MHz, Chloroform-d) δ 163.9, 152.4, 143.9, 141.7, 141.6, 141.4, 131.5, 128.8, 125.1, 119.0, 118.1, 117.1, 108.6, 83.3, 45.1, 28.2, 27.9; HRMS (ESI) calculated for C23H24ClN4O3 ⁺ [M+H] ⁺ 439.1541; found m/z 439.1539. Example 41. Synthesis of tert-Butyl 3-((2-methoxyphenyl)amino)-4-oxo-2-(pyridin-4- yl)-1,4,6,7-tetrahydro-5H-pyrrolo[3,2-c]pyridine-5-carboxyla te, 7u Synthesised according to GP2 using 5u (50.0 mg, 0.132 mmol) and 6a (18.7 µL, 0.198 mmol). Purified by silica gel chromatography using a 12 g SiO2 cartridge and a linear gradient of 0-100% EtOAc in heptane over 40 CV to give 7u (37 mg, 64%) as a yellow solid. ¹ H NMR (400 MHz, Chloroform-d) δ 10.56 (s, 1H), 8.31 (d, J = 5.4 Hz, 2H), 7.47 (s, 1H), 7.32 (d, J = 5.5 Hz, 2H), 6.81 (d, J = 8.0 Hz, 1H), 6.70 (t, J = 7.7 Hz, 1H), 6.54 (t, J = 7.6 Hz, 1H), 6.26 (d, J = 7.8 Hz, 1H), 4.05 (t, J = 6.3 Hz, 2H), 3.86 (s, 3H), 2.89 (t, J = 6.3 Hz, 2H), 1.51 (s, 9H); ¹³ C NMR (101 MHz, Methanol-d4) δ 174.6, 163.0, 158.8, 158.5, 150.3, 150.1, 143.0, 139.0, 130.2, 129.5, 129.4, 129.1, 123.1, 120.4, 118.6, 93.0, 65.2, 55.8, 42.0, 37.3; HRMS (ESI) calculated for C24H26N4O4 ⁺ [M+H] ⁺ 435.2032; found m/z 435.2032. Example 42. Synthesis of tert-Butyl 3-((4-(ethoxycarbonyl)phenyl)amino)-4-oxo-2- (pyridin-4-yl)-1,4,6,7-tetrahydro-5H-pyrrolo[3,2-c]pyridine- 5-carboxylate, 7v Synthesised according to GP2 using 5v (50.0 mg, 0.119 mmol) and 6a (16.8 µL, 0.178 mmol). Purified by silica gel chromatography using a 12 g SiO2 cartridge and a linear gradient of 0-100% EtOAc in heptane over 10 CV, followed by a linear gradient of 0-10% MeOH in DCM over 20 CV to give 7v (35 mg, 61%) as a yellow solid. ¹ H NMR (400 MHz, Chloroform-d) δ 11.42 (s, 1H), 8.29 (d, J = 6.0 Hz, 2H), 7.74 (d, J = 8.5 Hz, 2H), 7.39 (s, 1H), 7.31 (d, J = 6.0 Hz, 2H), 6.60 (d, J = 8.5 Hz, 2H), 4.27 (q, J = 7.1 Hz, 2H), 4.06 (t, J = 6.3 Hz, 2H), 2.90 (t, J = 6.3 Hz, 2H), 1.52 (s, 9H), 1.32 (t, J = 7.1 Hz, 3H); ¹³ C NMR (101 MHz, Chloroform-d) δ 167.2, 164.2, 153.1, 148.0, 139.6, 139.4, 131.4, 127.5, 121.7, 120.1, 119.5, 115.2, 109.6, 83.5, 61.0, 45.7, 28.8, 28.5, 23.2, 14.8; HRMS (ESI) calculated for C26H29N4O5 ⁺ [M+H] ⁺ 477.2138; found m/z 477.2138. Example 43. Synthesis of tert-Butyl 7-methyl-4-oxo-3-(phenylamino)-2-(pyridin-2-yl)- 1,4,6,7-tetrahydro-5H-pyrrolo[3,2-c]pyridine-5-carboxylate, 7y Synthesised according to GP2 using 5y (100 mg, 0.287 mmol) and 6a (39.0 µL, 0.431 mmol). Purified by silica gel chromatography using a 24 g SiO2 cartridge and a linear gradient of 20-100% EtOAc in heptane over 13 CV, followed by a linear gradient of 0- 10% MeOH in DCM over 13 CV to give 7y (75 mg, 65%) as a yellow solid. ¹ H NMR (400 MHz, Chloroform-d) δ 9.94 (br s, 1H), 8.30 – 8.24 (m, 2H), 7.37 (s, 1H), 7.28 (d, J = 5.7 Hz, 2H), 7.06 (t, J = 7.6 Hz, 2H), 6.76 (t, J = 7.3 Hz, 1H), 6.65 (d, J = 7.9 Hz, 2H), 4.15 (dd, J = 13.1, 4.6 Hz, 1H), 3.70 (dd, J = 13.0, 8.3 Hz, 1H), 3.26 – 3.13 (m, 1H), 1.55 (s, 9H), 1.37 (d, J = 7.3 Hz, 3H); ¹³ C NMR (101 MHz, Chloroform-d) δ 163.8, 153.0, 148.5, 143.2, 142.9, 139.1, 129.6, 128.8, 120.2, 118.9, 117.8, 116.3, 108.0, 83.0, 51.9, 28.5, 28.2, 15.9; HRMS (ESI) calculated for C24H27N4O3 ⁺ [M+H] ⁺ 419.2083; found m/z 419.2082. Example 45. Synthesis of 3-((3-fluoro-2-methoxyphenyl)amino)-2-(3-(2-methoxy-2- methylpropoxy)pyridin-4-yl)-1,5,6,7-tetrahydro-4H-pyrrolo[3, 2-c]pyridin-4-one (18) 3-(2-Methoxy-2-methylpropoxy)isonicotinonitrile, 13 ⁴ According to a modified literature procedure, ⁴ 2-methoxy-2-methylpropan-1-ol (285 µL, 2.60 mmol, 1.20 eq) was added to a suspension of NaH (60% dispersion in mineral oil, 99.6 mg, 2.49 mmol, 1.15 eq) in DMF (6.00 mL) at 0 °C and the mixture stirred at that temperature for 15 minutes.3-chloropyridine-4-carbonitrile (300 mg, 2.17 mmol, 1.00 eq) was added and the mixture stirred for 2 hours, allowing to warm to room temperature. The reaction mixture was quenched with water (60 mL) and extracted with EtOAc (3 × 30 mL). The combined organic extracts were washed with water and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography using a 24 g SiO2 cartridge and a linear gradient of 5-70% EtOAc in heptane to afford 13 (392 mg, 88%) as a white solid, ¹ H NMR (400 MHz, Chloroform-d) δ 8.72 (s, 1H), 8.38 (d, J = 4.8 Hz, 1H), 7.77 (dd, J = 4.8, 0.7 Hz, 1H), 4.19 (s, 2H), 3.17 (s, 3H), 1.24 (s, 6H); ¹³ C NMR (101 MHz, DMSO-d6) δ 155.2, 142.7, 137.3, 126.5, 114.8, 108.3, 75.2, 74.3, 49.8, 22.3; HRMS (ESI) calculated for C11H15N2O2 ⁺ [M+H] ⁺ 207.1134; found m/z 207.1138. The data matched those of the literature. ⁴ 3-(2-Methoxy-2-methylpropoxy)isonicotinaldehyde, 14 DIBAL-H (1.0 M in toluene, 2.18 mL, 0.728 mmol, 1.50 eq) was added dropwise to a solution of 13 (300 mg, 1.46 mmol, 1.00 eq) in toluene (15.0 mL) at 0 °C and the mixture stirred at that temperature for 4 hours. DIBAL-H (1.0 M in toluene, 727 µL, 0.728 mmol, 0.500 eq) was added and the mixture stirred for a further 2 hours. The mixture was quenched with MeOH and then diluted with 0.1 m HCl (50 mL). The mixture was extracted with DCM (3 × 40 mL) and the combined organic extracts were dried over Na ² SO ⁴ , filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography using a 24 g SiO2 cartridge and a linear gradient of 0-6% MeOH in DCM to afford 14 (185 mg, 61%) as an orange solid. ¹ H NMR (400 MHz, Chloroform-d) δ 10.58 (s, 1H), 8.55 (s, 1H), 8.40 (d, J = 4.8 Hz, 1H), 7.59 (d, J = 4.8 Hz, 1H), 4.06 (s, 2H), 3.29 (s, 3H), 1.34 (s, 6H); ¹³ C NMR (101 MHz, Chloroform-d) δ 188.9, 155.3, 143.1, 137.2, 129.4, 119.9, 75.3, 74.2, 49.9, 22.1; HRMS (ESI) calculated for C11H15NO3 ⁺ [M+H] ⁺ 210.1130; found m/z 210.1134. 1-Fluoro-3-isothiocyanato-2-methoxybenzene, 16 ⁵ According to a literature procedure, ⁵ thiophosgene (272 µL, 3.54 mmol, 1.00 eq) was added to a stirred mixture of 3-fluoro-2-methoxyaniline (500 mg, 3.54 mmol, 1.00 eq) in DCM (5.00 mL) and saturated aqueous NaHCO3 (5.00 mL) and the mixture stirred at 0 °C for 2 hours. The layers were separated, and the aqueous layer extracted with DCM (2 × 10 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated under reduced pressure to afford 16 (616 mg, 95%) as a brown oil that was used without further purification ¹ H NMR (400 MHz, Chloroform-d) δ 7.09 – 6.79 (m, 3H), 4.03 (d, J = 1.9 Hz, 3H); ¹⁹ F NMR (376 MHz, Chloroform-d) δ –129.1. The data matched those of the literature. ⁵ tert-Butyl 5-((3-fluoro-2-methoxyphenyl)carbamothioyl)-4-hydroxy-6-oxo- 3,6- dihydropyridine-1(2H)-carboxylate, 17 ⁵ Synthesised according to GP1 using tert-butyl 2,4-dioxopiperidine-1-carboxylate (710 mg, 3.33 mmol) and 16 (610 mg, 3.33 mmol). Purified by silica gel chromatography using a 40 g SiO2 cartridge and a linear gradient of 0-50% EtOAc in heptane over 15 CV to give 17 (960 mg, 73%) as an off-white solid. ¹ H NMR (400 MHz, DMSO-d6) δ 13.38 (s, 1H), 7.57 (dt, J = 8.1, 1.5 Hz, 1H), 7.26 (ddd, J = 11.3, 8.4, 1.6 Hz, 1H), 7.16 (td, J = 8.3, 5.8 Hz, 1H), 3.86 (d, J = 1.5 Hz, 3H), 3.79 (t, J = 6.5 Hz, 2H), 2.89 (t, J = 6.5 Hz, 2H), 1.49 (s, 9H); ¹³ C NMR (101 MHz, DMSO-d6) δ 189.9, 186.2, 155.6 (d, J = 245.0 Hz), 152.3, 132.4 (d, J = 4.3 Hz), 123.8 (d, J = 8.7 Hz), 123.1 (d, J = 3.1 Hz), 116.1 (d, J = 18.9 Hz), 103.1, 83.1, 62.0 (d, J = 4.9 Hz), 31.4, 28.1; ¹⁹ F NMR (376 MHz, DMSO-d6) δ –130.0; HRMS (ESI) calculated for C18H20FN2O5S ^– [M-H] ^– 395.1077; found m/z 395.1077. The data matched those of the literature. ⁵ 18 ⁴ A solution of 14 (79.2 mg, 0.378 mmol, 1.50 eq) in 1,4-dioxane (1.00 mL) was added dropwise, over 2.5 hours using a syringe pump, to a mixture of 17 (100 mg, 0.252 mmol, 1.00 eq) and NH4OAc (97.2 mg, 1.26 mmol, 5.00 eq) in toluene (1 mL) at 90 °C and the mixture stirred at 90 °C for 18 hours and then cooled to room temperature. The reaction mixture was concentrated to around 0.5 mL and EtOAc (1 mL) was added. HCl in 1,4- dioxane (4.0 m, 0.63 mL, 2.52 mmol, 10.0 eq) was added with vigorous stirring and the mixture stirred for 1 hour at room temperature. The reaction mixture was quenched with saturated aqueous NaHCO3 (25 mL) and diluted with DCM (25 mL). The layers were separated, and the aqueous layer extracted with DCM (2 × 10 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue wasp purified by silica gel chromatography using a 24 g SiO2 cartridge and a linear gradient of 20-100% EtOAc in heptane over 13 CV, followed by a linear gradient of 0- 10% MeOH in DCM over 20 CV to give 18 (64 mg, 56%) as an off-white solid. ¹ H NMR (400 MHz, DMSO-d6) δ 11.17 (s, 1H), 8.42 (s, 1H), 8.02 (d, J = 5.1 Hz, 1H), 7.51 (s, 1H), 7.29 (d, J = 5.1 Hz, 1H), 7.16 (t, J = 2.6 Hz, 1H), 6.67 (td, J = 8.3, 6.1 Hz, 1H), 6.51 (ddd, J = 11.0, 8.4, 1.5 Hz, 1H), 6.04 (dt, J = 8.3, 1.3 Hz, 1H), 4.19 (s, 2H), 3.92 (d, J = 0.8 Hz, 3H), 3.43 (td, J = 6.9, 2.5 Hz, 2H), 3.26 (s, 3H), 2.84 (t, J = 6.8 Hz, 2H), 1.28 (s, 6H); ¹³ C NMR (101 MHz, DMSO-d6) δ 165.8, 155.8 (d, J = 242.0 Hz), 150.2, 143.3, 140.0 (d, J = 4.7 Hz), 137.4, 136.1, 135.5 (d, J = 13.4 Hz), 127.8, 125.9, 124.0 (d, J = 9.8 Hz), 120.4, 117.1, 109.2, 108.1, 106.2 (d, J = 19.0 Hz), 75.5, 75.1, 49.7, 40.5, 22.5, 22.1; 1 ⁹ F NMR (376 MHz, DMSO-d6) δ –132.7; HRMS (ESI) calculated for C24H28FN4O4 [M+H] ⁺ 455.2095; found m/z 455.2098. The data matched those of the literature. ⁴ Example 46. Scale-up synthesis of 2-(3-bromopyridin-4-yl)-3-((3-chloro-2- methoxyphenyl)amino)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyr idin-4-one (Compound 102) Step 1: ➢ Different base (TEA, DIIEA and DBU) were compared on 5 g scale reactions, DIEA provided 98.2 A% IPC purity. ➢ Step 2: ➢ Different bases (DBU, DIEA and TEA), equivalents of base, and temperature were screened using 20 V of IPAc as solvent, 1.1 equivalents of DBU provided 90.4 A% IPC purity. ➢ ➢ Different bases (DBU, DIEA and TEA), equivalents of base, and temperature were screened using 20 V of IPAc as solvent, 1.1 equivalents of DBU provided 90.4 A% IPC purity. This condition was used for scale up. Solubility data of Compound 2 & Compound 2 containing DBU Step 1&2: (telescope procedure)

➢ Step 3:

Step 3: HNMR Data of Compound 101 is included in FIG.2. Solubility data of Compound 101 Step 3&4 The crystallization for purification of Compound 102 with 5 V of different solvents (DCM, MeCN, MTBE, THF, MeOH, EtOAc and toluene) were tried, however, Compound 102 has not been dissolved in all these solvents at reflux except for THF. ✓ THF as solvent for purification, the purity of Compound 102 increased to 98.6 A% from 95.3 A%, the yield was about 40%. ✓ Toluene as solvent for purification, the residual S reduced to 0.056% w/w from 1.0% w/w by IC and the QNMR increased to 95.7% from 87.1%, and HPLC purity 97.1 A). Solubility data of Compound 102

➢ To upgrade the purity of Compound 102 and reduce the content of sulfur in Compound 102, the crystallization/slurry with different solvents were tried, DMAc/toluene condition gave the best result for purity upgrade (from 95.2 A% to 99.2 A%), NMP/water and DMAc/water conditions gave the best S removal capacity (from 2.24% to 0.10%). ➢ 5 g of crude Compound 102 was purified using DMAc/toluene condition.3.6 g of Compound 102 was obtained with 99.1 A% purity (DMAC are not integrated) and 72% yield (uncorrected by QNMR). The residual S was 0.35% and the potency by QNMR was 88%. 1H NMR of compound 102 is included in FIG.3. Around 12% of DMAC was remained in Compound 102. ➢ To remove DMAc, 3.5 g of Compound 102 (QNMR: 88%) was re-slurried with 10 V of water, 2.7 g of Compound 102 was obtained with 99.2 A% purity and 77% yield (uncorrected by QNMR). ➢ To increase the yield of crystallization (DMAc/toluene system), 2 V of DMAC and 7 V of toluene was tried, 99.2 A% purity (DMAC are not integrated) of Compound 102 was obtained. Compound 102 ➢ 10 g of crude Compound 102 was purified using 2 V of DMAC / 7 V of toluene, 8.5 g of Compound 102 was obtained with 99.2 A% purity (DMAC are not integrated) and 85% yield (uncorrected by QNMR). The 8.5 g of Compound 102 is being re-slurried with water to remove DMAc. The LC-MS spectrum and a figure of powder of compound 102 are included in FIGS.4A-4B.

10 g of Compound 102 (assay: 88%) was purified via stage 1 (crystallization by DMAc/toluene) and stage 2 (slurry with water): ➢ Stage 1, 8.5 g (containing ~12% w/w of DMAc by QNMR) of Compound 102 was obtained with 99.0 A% purity (DMAc is not integrated) and 85% yield (uncorrected by QNMR). ➢ Stage 2, 6.5 g of Compound 102 was obtained with 99.7 A% purity and 99.5% potency by QNMR. The yield was 65% yield (for 10 g of crude Compound 102) and the residual S was 119 ppm. In order to reduce the loss during purification, different ratio of DMAC/toluene (1 V/3 V, 0.5 V/3.5 V) were tried on 5 g scale: ➢ DMAC/toluene = 1 V/3 V, 3.5 g of Compound 102 was obtained with 99.6 A% purity and 99.5% potency by QNMR, the recovery yield was 70% and the residual S was 119 ppm. ➢ DMAC/toluene = 0.5 V/3.5 V, 3.6 g of Compound 102 was obtained with 96.9 A% purity and 98.5% potency by QNMR, the recovery yield was 72% and the residual S was 423 ppm. ➢ The mass balance data of step 3&4 was collected, based on the mass balance data, around 20% of product was lost during work-up and purification.

300 g scale of demo batch provided 57.5 A% IPC purity in step 3 (assay yield at the end of reaction: 61.9%) and 58.0 A% IPC purity in step 4, after work-up, 143 g of Compound 102 was obtained with 99.4 A% purity and 44% yield (corrected by QNMR).

Example 47. Kilogram-scale synthesis of 2-(3-bromopyridin-4-yl)-3-((3-chloro-2- methoxyphenyl)amino)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyr idin-4-one (Compound 102) P ^{roduction Summary} Production of Step 1 & 2 1) Process Route 2) Process Description Preparation of 1-chloro-3-isothiocyanato-2-methoxybenzene, 1 Under nitrogen atmosphere, spray isopropyl acetate (IPAC) into the reactor, heat reflux for at least 30 minutes and cool down to 20±10℃, through the feed line, filter tank, pneumatic pump, liquid transfer line, transfer another reactor, heat reflux for at least 30 minutes and cool down to 20±10℃, put bucket. Drying reaction kettle, blow-dry discharge pipeline, pressure filter tank, pneumatic pump, liquid transfer pipeline. 1 ^st Separation Stand for at least 30 minutes under nitrogen, separate, collect the aqueous phase and organic phase. 1 ^st Extraction Under N2, charge aqueous phase to a reactor, adjust the temperature to 20±5 C. Charge IPAc (3.00 V) to the reactor at 20±5 C, stir for at least 20 minutes, stand for at least 30 minutes, separate, collect the aqueous phase and organic phase. Take sample of aqueous phase for product loss test (IPM), the organic phase waits for combination and washing. Washing Under N2, charge 10% sodium chloride aqueous solution (3.33 w/w) to reactor with the organic phase, adjust temperature to 20±5 C, stir for at least 20 minutes, stand for at least 30 minutes, separate, collect the organic phase and wait for 1 ^st concentration. ^{1st Concentration} Add the organic phase to the reactor through a fluid filter. Control the reactor inner temperature not more than 45 C or jacket temperature not more than 55 C and ^{concentrate until the volume is 1.0~1.5 V.} 2 ^nd Concentration Under N2, charge MeOH (3.00 V) to reactor. Control the reactor inner temperature not more than 45°C or jacket temperature not more than 55°C and concentrate until the volume is 1.0~1.5 V 3 ^rd concentration Under N ² , charge MeOH (3.00 V) to reactor. Control the reactor inner temperature not more than 45 C or jacket temperature not more than 55 C and concentrate until the volume is 1.0~1.5 V. Adjust temperature to 25±5 C. Charge MeOH (3.00 V) to reactor. Sample for GC analysis. Criterion is: the area% of IPAc≤5% and KF≤0.5%, if the area% of IPAc>5% or KF>0.5%, repeat the solvent exchange procedure with MeOH until the area% of IPAc ≤5% and KF≤0.5%. Sample for Q-NMR, report result. Discharge the concentration system in reactor to drum. Preparation of 1-chloro-3-isothiocyanato-2-methoxybenzene, 1 Charging and reaction Charge IPAC (20.00 V) to reactor and start agitation under nitrogen. Adjust the temperature to 20±5℃. Take a sample for KF after stirring for at least 5 minutes, criterion: KF is no more than 0.08%. if not, discharge and charge new solvent. Then charge 3-Chloro-2-methoxyaniline (SM11.00eq) and DIPEA (2.50eq) to the reactor in turn. Cool to 0-5°C and charge Thiophosgene (0.98eq) dropwise to the reactor at 5±5°C ( It is recommended to add at least 2 hour). Addition completely, continue to control temperature at 5±5°C, agitate for at least 2 hour. Sample for HPLC analysis, the criterion: the area% of SM1≤3.0% and the total sample times should be no more than two times. Sample for IPM analysis, report content of Thiophosgene. Quenched Under nitrogen and adjust the temperature of hydrochloric acid solution to 5-10 C, replacement with nitrogen three times. Charge reaction system to 3 M hydrochloric acid aqueous (3.00 V) at 10±5 C. Take a sample for pH=1~4. Stir for at least 30 minutes, retest the pH, criterion is pH=1~4; if pH>4, charge 3 M hydrochloric acid aqueous solution to make sure the pH=1~4. Stir for at least 3 hours at 20±5 C (during stirring, pump nitrogen to remove hydrogen in the system). 4 ^th Concentration Control the inner temperature of the reactor not more than 45 C or jacket temperature not more than 55 C and concentrate until the volume is 3~4 V. Adjust temperature to 20±5 C. 2 ^nd Separation Charge soften water (3.00 V) to a reactor at 20±5 C under nitrogen and start to stir. Dropwise 10% sodium carbonate aqueous solution (6.67 w/w) to reaction when temperature 20±5 C. Take a sample for pH=8~9, stir at least for 30 minutes, retest pH=8~9. If not, charge sodium carbonate into reactor at 20±5 C until pH=8~9, stir at least for 30 minutes, retest pH=8~9. Charge IPAc (5.00 V), stir for at least 20 minutes, stand for at least 30 minutes, separate, collect the aqueous phase and organic phase. 2 ^nd Extraction Under N2, charge aqueous phase to a reactor, adjust the temperature to 20±5 C. Charge IPAc (5.00 V) to the reactor at 20±5 C, stir for at least 20 minutes, stand for at least 30 minutes, separate, collect the aqueous phase and organic phase. 3 ^rd Extraction Under N2, charge aqueous phase to a reactor, adjust the temperature to 20±5 C. Charge IPAc (5.00 V) to the reactor at 20±5 C, stir for at least 20 minutes, stand for at least 30 minutes, separate, collect the aqueous phase and organic phase. combine the organic phase. Take sample of aqueous phase for product loss test (IPM), the organic phase wait for concentration. 5 ^th Concentration Add the organic phase to the reactor through a fluid filter. Control the inner temperature of the reactor not more than 45 C or jacket temperature not more than 55 C and concentrate until the volume is 1.0~1.5 V. 6 ^th concentration Charge DCM (5.00 V) to reactor. Control the inner temperature of the reactor not more than 45 C or jacket temperature not more than 55 C and concentrate until the volume is 1.0~1.5 V. 7 ^th concentration Charge DCM (5.00 V) to reactor. Control the inner temperature of the reactor not more than 45 C or jacket temperature not more than 55 C and concentrate until the volume is 1.0~1.5 V. Adjust temperature to 25±5 C. Charge DCM (4.00 V) to reactor. Sample for GC analysis. Criterion is: the area% of MeOH≤5% and the area% of IPAc≤20% and KF≤ 0.2%, if the area% of MeOH>5% or IPAc>20% or KF>0.2%, repeat the solvent exchange procedure with DCM until the area% of MeOH≤5% and the area% of IPAc≤20% and KF≤0.2%. Feeding (liquid product) Sample for HPLC and Q-NMR test. Report result. Tranfer the product in the reactor into drums, weight and label. Store at room temperature. 3) Process of step 1 & 2 1. Charge IPAC (20 V) to a reactor under nitrogen. 2. Charge SM1 (1.0 eq.) and TEA (2.5 eq.) to the reactor and start to stir at 20±5 C. 3. Cool to 5±5 C. 4. Charge SCCl2 (1.0 eq.) drop-wise to the reactor at 5±5 C. 5. Stir 2 h at 5±5 C. 6. Sample for HPLC analysis. 7. Filtrate. 8. Charge the IPAC solution and SM2 (1.0 eq.) to the reactor under nitrogen. 9. Cool to 5±5 C. 10. Charge DBU (1.1 eq.) drop-wise to the reactor. 11. Stir for 12 h at 20±5 C. 12. Sample for HPLC analysis. 13. Adjust pH of reaction to 5-6 using aq. citric acid (0.2 M) at 20±5 C. 14. Separate and wash the organic phase with 5% aq. NaHCO3 (5 V) at 20±5 C. 15. Wash the organic phase with 15% aq. NaCl (5 V) at 20±5 C. 16. Concentrate the organic phase to 3-4 V at 45±5 C. 17. Add MeOH (10 V) and concentrate to 4-5 V at 45±5 C. 18. Add MeOH (10 V) and concentrate to 4-5 V at 45±5 C. 19. Stir for 1h at 20±5 C. 20. Filter and wash filter the cake with MeOH (2 V) 21. Collect and dry the cake at 40±5 C. 4) Production Data Summary 5) Results • 20 g scale use-test worked well with 97.9 A% IPC purity in step 1 and 88.8 A% IPC purity in step 2. • 29 kg of production batch worked well with 97.7 A% IPC purity in step 1 and 85.0 A% IPC purity in step2, after work-up, 60kg of comp. 2 was obtained with 99.5 A% IPC purity and 78.9% yield (uncorrected by QNMR). Production of Step 3 & 4 1) Process Route 2) Process Description Preparation of 6% the solution of citric acid Under nitrogen, charge soften water（24.00V）to reactor, start agitation. Charge citric acid （1.51w/w）to the reactor, adjust the temp to 20±10℃, stir for dissolved, discharge into drum for temporary storage. Charging and reaction Charge IPAC (8.00 V) to reactor which store the solution of 1-chloro-3-isothiocyanato-2- methoxybenzene and start agitation under nitrogen. Adjust the temperature to 20±5℃. Take a sample for KF after stirring for at least 5 minutes, report the result. Then charge 1,8- Diazabicyclo[5.4.0]undec-7-ene (DBU) at 20±5℃. Cool to 0-5°C and charge Diazabicyclo (1.10eq) dropwise to the reactor at 5±5°C (It is recommended to add at least 1 hour). Addition completely, adjust temperature to 20±5°C（It is recommended that the temperature rise for at least 1 hour）, agitate for at least 12 hour. Sample for HPLC analysis, the criterion: the area% of 1- chloro-3-isothiocyanato-2-methoxybenzene (1) ≤5.0%. If not, agitate for at least 8 hours, sample for HPLC until area% of 1-chloro-3-isothiocyanato-2-methoxybenzene (1) ≤5.0%. Sample for IPM analysis, report content of Thiophosgene. Quenching and Separation Charge 6% citric acid solution to reaction system to adjust PH to 5-6 at 20±5°C. Stir at least 20 mins, test pH=5-6. Stir at least 2 hours at 20±5°C(System drum nitrogen). Sample for Hydrogen sulfide detected. The hydrogen sulfide concentration in the head space is less than 1ppm. If it is unqualified, continue to blow nitrogen until it meets the standard. hold at least for 30mins, separate, collect the organic phase. Washing Charge soften water（5.00V）to organic phase, adjust temperatue to 20±5°C, stir at least 30 mins, hold at least 30mins, separate, collect organic treat concentrate. 1 ^st Concentration Control the jacket temperature is no more than 45℃ and inner temperature is no more than 35℃. Concentration to 5-6V. 2 ^nd concentration Adjust temperature to 20±10℃, charge methanol（10.00V）into reactor. Control the jacket temperature is no more than 45℃ and inner temperature is no more than 35℃. Concentration to 5-6V. 3 ^rd concentration Adjust temperature to 20±10℃, charge methanol（10.00V）into reactor. Control the jacket temperature is no more than 45℃ and inner temperature is no more than 35℃. Concentration to 5-6V. Adjust temperature to 20±5℃, sample for HPLC and GC(IPM), Report content of 2 and area% of IPAC in mother liquor. Feeding (liquid product) Sample for HPLC and Q-NMR test. Report result. Transfer concentration in the reactor into drums, weight and label. Store at room temperature. 3) Process of Step 3 & 4 1. Charged tert-butyl 5-((3-chloro-2-methoxyphenyl)carbamothioyl)-4-hydroxy-6-oxo- 3,6- dihydropyridine-1(2H)-carboxylate (2) (1.0 eq.) and NH ₄ OAc (5.0 eq.) to toluene (7.5 V). 2 _. Heated to 95±5 C and charged pre-prepared solution of SM3 (1.5 eq. in toluene/ 1,4- dioxane 15 V, 1/1) drop-wise to the reactor at 95±5 C. 3. Stirred for 16 h at 95±5 C and sampled for HPLC analysis, criterion: tert-butyl 5-((3- chloro-2-methoxyphenyl)carbamothioyl)-4-hydroxy-6-oxo-3,6-di hydropyridine-1(2H)- carboxylate (2) ≤ 5.0%. 4 _. Concentrated to 3-4 V at 50±5 C and charged EA (6 V) to the reactor. 5. Charged 4 M HCl/EtOH (3 V) drop-wise to the reactor at 25±5 C and stirred for at least 3 h. 6. Sampled for HPLC analysis, criterion: tert-butyl 2-(3-bromopyridin-4-yl)-3-((3-chloro-2- methoxyphenyl)amino)-4-oxo-1,4,6,7-tetrahydro-5H-pyrrolo[3,2 -c]pyridine-5- carboxylate (compound 101) ≤ 2.0%. 7. Filtered and washed the cake with EA (1 V). 8. Charged filter cake to EA/MeOH=10:1 (10 V). 9 _. Charged 10% K ₂ CO ₃ aq. (10 V) to the reactor at 25±5 C and stirred for at least 5 h. (Note: pH: 8~9) 10. Filtered and washed the cake with MTBE (1 V) and dried for 16 h at 50 C under N ₂ . 11. Changed 1 V of DMAc and 3 V of toluene to a reactor and charged crude (compound 102) to the reactor. 12. Heated to 75±5C and stirred for at least 4 h. 13. Cooled to 45±5C and charged 5 V of toluene drop-wise to the reactor. 14. Stirred for at least 2 h at 45±5C. 15. Cool to 10±5 C and stir for at least 3 h at 10±5 C. 16. Filtered and washed with toluene (1 V). 17. Changed 10 V of water and wet cake to a reactor. 18. Heated to 50±5C and stirred for at least 3 h at 50±5 C. 1 _9. Cooled to 10±5C and stirred for at least 3h at 10±5 C. 20. Filtered and washed with water (1~2 V). 21. Dried for 16 h at 50±5 C under N ₂ . Production Data Summary 4) Results ➢ The first 30.3 kg scale of production batch worked well with 57.9 A% IPC purity in step 3, the assay yield of compound 101 at the end of reaction was 61.5%. ➢ The second 30.3 kg scale of production batch worked well with 60.1 A% IPC purity in step 3, the assay yield of compound 101 at the end of reaction was 62.5%. ➢ After concentrating separately, the two batches were combined for step 4 reaction directly. The step 4 reaction worked well with 63.1 A% IPC purity. ➢ After work-up and purification, 36 kg of compound 102 was obtained with 99.0 A% purity (toluene wasn't integrated) and 54.8% yield (uncorrected by QNMR). Example 48. Synthesis of tert-Butyl 3-((3-chloro-2-methoxyphenyl)amino)-4-oxo-2- (pyridin-4-yl)-1,4,6,7-tetrahydro-5H-pyrrolo[3,2-c]pyridine- 5-carboxylate A solution of isonicotinaldehyde (1.71 mL, 18.2 mmol, 1.5 eq) in 1,4-dioxane (50 mL) was added dropwise over 2.5 hours with a syringe pump to a preheated, stirred, solution of tert- butyl 5-((3-chloro-2-methoxyphenyl)carbamothioyl)-4-hydroxy-6-oxo- 3,6- dihydropyridine-1(2H)-carboxylate (5.00 g, 12.1 mmol, 1.0 eq) and NH4OAc (4.67 g, 60.6 mmol, 5.0 eq) in toluene (50 mL) at 90 °C. The reaction mixture was stirred at 90 °C for 20 hours and then concentrated under reduced pressure. The crude residue was adsorbed onto silica and then purified by silica gel chromatography (25-100% heptane/EtOAc and then 0-10% MeOH in DCM) to afford tert-butyl 3-((3-chloro-2-methoxyphenyl)amino)-4- oxo-2-(pyridin-4-yl)-1,4,6,7-tetrahydro-5H-pyrrolo[3,2-c]pyr idine-5-carboxylate (3.36 g, 59% yield) as an orange solid. LCMS (ES, m/z): [M+H] ⁺ : 469.2; ¹ H NMR (400 MHz, DMSO-d6) δ 12.14 (s, 1H), 8.45 (d, J = 5.0 Hz, 2H), 7.47 (d, J = 4.9 Hz, 2H), 7.36 (s, 1H), 6.73 (d, J = 7.5 Hz, 2H), 6.16 (dt, J = 7.1, 2.1 Hz, 1H), 3.97 (t, J = 6.3 Hz, 2H), 3.91 (s, 3H), 2.98 (t, J = 6.3 Hz, 2H), 1.44 (s, 9H); ¹³ C NMR (101 MHz, DMSO-d6) δ 162.3, 153.2, 150.3, 143.7, 140.7, 140.1, 138.3, 127.0, 125.6, 125.4, 122.3, 118.9, 118.8, 112.2, 109.8, 81.9, 60.2, 45.6, 28.2, 22.8. References 1. Graham, K.; Klar, U.; Briem, H.; Schulze, V.; Siemeister, G.; Lienau, P.; Tempel, R.; Balint, J.4H-Pyrrolo[3,2-c]pyridin-4-one Derivatives. WO2016/120196 A1, 2016. 2. Siegel, F.; Korr, D.; Schröder, J.; Siegel, S.; Greulich, H.; Kaplan, B.; Meyerson, M. 4H-Pyrrolo[3,2-c]pyridin-4-one Derivatives. WO2020/216774 A1, 2020. 3. Jagodziński, T. S.; Sośnicki, J. G.; Struk, L. ARKIVOC 2017, 5, 43–57. 4. Siegel, S.; Siegel, F.; Schulze, V.; Berger, M.; Graham, K.; Klar, U.; Eis, K.; Sülzle, D.; Bömer, U.; Korr, D.; Peterson, K.; Mönning, U.; Eberspächer, U.; Moosmayer, D.; Meyerson, M.; Greulich, H.; Kaplan, B.; Harb, H. Y.; Dinh, P. M.4H-Pyrrolo[3,2- c]pyridin-4-one Derivatives. WO2019/081486 A1, 2019. 5. Milgram, B. C.; White, R. D.; St. Jean Jr., D.; Guzman-Perez, A. Pyrrolo[3,2- c]pyridin-4-one Derivatives Useful in the Treatment of Cancer. WO2022/066734 A1, 2022.