Pharmaceutical compounds for the treatment of complement mediated disorders

Abstract

This disclosure provides compounds, compositions, and methods to treat medical disorders, such as complement-mediated disorders, including complement C1s-mediated disorders.

Description

[0001] ALXN-0780-PCT01-NP PHARMACEUTICAL COMPOUNDS FOR THE TREATMENT OF COMPLEMENT MEDIATED DISORDERS Field of the Disclosure Herein are provided pharmaceutical compounds to treat medical disorders, such as complement- mediated disorders, including complement C1-mediated disorders. Background of the Disclosure The complement system is a part of the innate immune system which does not adapt to changes over the course of the subject’s life but is recruited and used by the adaptive immune system. For example, it assists, or complements, the ability of antibodies and phagocytic cells to clear pathogens. This sophisticated regulatory pathway allows rapid reaction to pathogenic organisms while protecting host cells from destruction. Over thirty proteins and protein fragments make up the complement system. These proteins act through opsonization (enhancing phagocytosis of antigens), chemotaxis (attracting macrophages and neutrophils), cell lysis (rupturing membranes of foreign cells), and agglutination (clustering and binding of pathogens together). The complement system has three pathways: classical, alternative, and lectin. The classical pathway is triggered by antibody-antigen complexes with the antibody isotypes IgG and IgM. The antibody-antigen complex binds to C1 and this initiates the cleavage of C4 and C2 to generate C3 convertase that then splits C3 into C3a and C3b. C3a interacts with its C3a receptor to recruit leukocytes, while C3b binds to C3 convertase to form C5 convertase. C5 convertase cleaves C5 into C5a and C5b. Similar to C3a, C5a interacts with its C5a receptor to recruit leukocytes, but C5b interacts with C6, C7, C8, and C8 and together these proteins form the cylindrical membrane attack complex (MAC) that causes the cell to swell and burst. These immune responses can be inhibited by preventing C1 from being able to bind the antibody-antigen complex. Given the range of serious diseases mediated by a disfunction of the complement system, there is a clear medical need to provide pharmaceutically acceptable compounds, methods, compositions, and methods of manufacture to inhibit the complement system in a patient in need thereof. Therefore, the present disclosure provides compounds and their uses and compositions to treat disorders arising from or amplified by a disfunction of the complement system. The present disclosure also provides compounds, uses, compositions, combinations, and processes of manufacture that inhibit C1s (complement C1 esterase) and thus can treat disorders mediated by C1s. Summary The present disclosure provides compounds, compositions, and methods for treating a disorder mediated by the complement cascade (including a dysfunctional cascade), a disorder or abnormality of a cell that adversely affects the ability of the cell to engage in or respond to normal complement activity including for example, the classical complement pathway, or an undesired complement-mediated response to a medical treatment, such as surgery or other medical procedure or a pharmaceutical or biopharmaceutical drug administration, a blood transfusion, or other allogenic tissue or fluid administration. In some embodiments, ALXN-0780-PCT01-NP the active compound may act as an inhibitor of the complement classical pathway by inhibiting complement C1s. Without wishing to be bound by theory, the present disclosure is based, in part, on the unexpected discovery that compounds of the disclosure exhibit advantageous properties over other C1s inhibitors (e.g., the compounds described in WO2020 / 198062, WO2022 / 066774, WO2023 / 183405, WO2024 / 035686, and WO2024 / 044098), such as improved C1s inhibiting activity, improved classical pathway hemolysis inhibiting activity, improved Caco-2 permeability, improved oral bioavailability, improved C1s selectivity (e.g., over other proteases, such as MASP-2), improved physiochemical properties, improved metabolic stability, and / or reduced cardiotoxicity (e.g., as measured by a hERG assay). In one aspect, the present disclosure provides a compound of Formula (I): , or a pharmaceutically acceptable as defined herein. In another aspect, the composition including a compound disclosed herein (e.g., any one of the compounds of Formulas (I), (I’), and (I”), and Table 1) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient. In another aspect, the present disclosure provides a method of treating a complement C1 esterase (C1s) mediated disorder. The method includes administering to a subject in need thereof a therapeutically effective amount of a compound disclosed herein (e.g., any one of the compounds of Formulas (I), (I’), and (I”), and Table 1) or a pharmaceutically acceptable salt thereof. In another aspect, the present disclosure provides a method of inhibiting C1s activity in a subject. The method includes administering to the subject in need thereof a therapeutically effective amount of a compound disclosed herein (e.g., any one of the compounds of Formulas (I), (I’), and (I”), and Table 1) or a pharmaceutically acceptable salt thereof. In another aspect, the present disclosure provides a compound disclosed herein (e.g., any one of the compounds of Formulas (I), (I’), and (I”), and Table 1) or a pharmaceutically acceptable salt thereof, for use in the treatment of a C1s mediated disorder. In another aspect, the present disclosure provides a use of a compound disclosed herein (e.g., any one of the compounds of Formulas (I), (I’), and (I”), and Table 1) or a pharmaceutically acceptable salt thereof in the preparation a medicament for use in the treatment of a C1s mediated disorder. Definitions Compounds are described using standard nomenclature. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which the present disclosure belongs. The terms “a” and “an” do not denote a limitation of quantity, but rather denote the presence of at least one of the referenced items. The term “or” means “and / or.” Recitation of ranges of values are merely intended to serve as a shorthand method of referring individually to each separate value falling within the ALXN-0780-PCT01-NP range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. The endpoints of all ranges are included within the range and independently combinable. All methods described herein can be performed in a suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of examples, or exemplary language (e.g., “such as”), is intended merely as illustration, and does not pose a limitation on the scope of the invention. The term “absent,” as used herein in reference to a structural variable, refers to the lack of a substituent due to the valency of the atom to which the structural variable is attached. For example, for an =C(R2)- group, one of the R2 is a substituent (e.g., H), while the other is absent due to the valency of the carbon atom. The term “alkoxy,” as used herein, refers to a -OR radical, in which R is alkyl, as defined herein. The term “alkoxyalkyl,” as used herein, refers to a -ROR’ radical, in which R is alkylene and R’ is alkoxy, as defined herein. The term “alkyl,” as used herein, refers to a branched or straight-chain monovalent saturated aliphatic radical containing only C and H when unsubstituted. The monovalency of an alkyl group does not include the optional substituents on the alkyl group. For example, if an alkyl group is attached to a compound, monovalency of the alkyl group refers to its attachment to the compound and does not include any additional substituents that may be present on the alkyl group. In some embodiments, the alkyl group may contain, e.g., 1-8, 1-6, 1-4, or 1-2 carbon atoms (e.g., C1-C8, C1-C6, C1-C4, or C1-C2). Examples include, but are not limited to, methyl, ethyl, isobutyl, sec-butyl, tert-butyl, 2-methylpropyl, and 2,2-dimethylpropyl. The term “alkylene,” as used herein, refers to a divalent radical obtained by removing a hydrogen atom from a carbon atom of an alkyl group. The divalency of an alkylene group does not include the optional substituents on the alkylene group. Examples of alkylene groups include, but are not limited to, methylene, ethylene, and n-propylene. The term “amino,” as used herein, refers to a monovalent radical of formula -NH2. The term “aryl,” as used herein, refers to any monocyclic or fused ring bicyclic or multicyclic system containing only carbon atoms in the ring(s), which has the characteristics of aromaticity in terms of electron distribution throughout the entire ring system, e.g., phenyl, naphthyl, or phenanthryl. An aryl group may have, e.g., 6-16, 6-14, or 6-10 carbon ring atoms (e.g., C6-C16, C6-C14, C6-C10, C6, C10, C14, or C16). The term “arylalkyl,” as used herein, refers to a -RR’ radical, in which R’ is aryl, as defined herein, and R is alkylene, as defined herein. The term “aryloxy,” as used herein, refers to an -OR radical, in which R is aryl, as defined herein. The term “carbocyclyl,” as used herein, refers to a monovalent, saturated (i.e., cycloalkyl) or unsaturated, non-aromatic group (e.g., cycloalkenyl) which contains at least one carbon-carbon double bond and no carbon-carbon triple bonds) and only C and H when unsubstituted, which may be monocyclic, bicyclic, or multicyclic (e.g., tricyclic). A carbocyclyl may have, e.g., 3-14 carbons (e.g., a C3-C4, C3-C5, C3-C6, C3-C7, C3-C8, or C3-C14 carbocyclyl). Examples of carbocyclyls include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclohexenyl, cycloheptenyl, and fluorenyl. The term “carbocyclyl” also includes cyclic groups having a bridged multicyclic structure in which one or more carbons bridges two non- adjacent members of a monocyclic ring, e.g., bicyclo[2.2.1]heptyl. ALXN-0780-PCT01-NP The term “cycloalkylalkyl,” as used herein, refers to an -RR’ radical, in which R’ is cycloalkyl, as defined herein, and R is alkylene, as defined herein. The term “cycloalkyloxy,” as used herein, refers to an -OR radical, in which R is cycloalkyl, as defined herein. The term “halo,” as used herein, refers to a fluorine (fluoro; F), chlorine (chloro; Cl), bromine (bromo; Br), or iodine (iodo; I) radical. The term “haloalkyl,” as used herein, refers to an alkyl group, as defined herein, in which one or more H is replaced with halo, as defined herein. Examples of haloalkyl include, but are not limited to, CF3, CHF2, and CH2F. The term “haloalkoxy,” as used herein, refers to an -OR radical, in which R is haloalkyl, as defined herein. The term “heteroaryl,” as used herein, refers to a monocyclic, bicyclic, or multicyclic aromatic ring monocyclic, bicyclic, or multicyclic group containing 1, 2, 3, or 4 heteroatoms selected from N, O, S, B, and P (e.g., 1-4, 1-3, or 1 or 2 heteroatoms selected from N, O, and S) as ring atoms, with the remaining ring atoms being carbon. In some embodiments, a heteroaryl group is a bicyclic or tricyclic system containing at least one 5, 6, or 7 membered aromatic ring which contains from 1, 2, 3, or 4 heteroatoms selected from N, O, S, B, or P (e.g., 1-4, 1-3, or 1 or 2 heteroatoms selected from N, O, and S) as ring atoms, with the remaining ring atoms being carbon. In some embodiments, a heteroaryl group is a monocyclic aromatic ring having 5 or 6 ring atoms (i.e., 5- or 6-membered heteroaryl). In some embodiments, is a bicyclic aromatic ring system having 8 to 10 ring atoms (i.e., 8- to 10-membered bicyclic heteroaryl). Examples of heteroaryl groups include, but are not limited to, pyridinyl, imidazolyl, imidazopyridinyl, pyrimidinyl, pyrazolyl, triazolyl, pyrazinyl, furyl, thienyl, isoxazolyl, thiazolyl, oxadiazolyl, oxazolyl, isothiazolyl, pyrrolyl, quinolinyl, isoquinolinyl, tetrahydroisoquinolinyl, indolyl, benzimidazolyl, benzofuranyl, cinnolinyl, indazolyl, indolizinyl, phthalazinyl, pyridazinyl, triazinyl, isoindolyl, pteridinyl, purinyl, oxadiazolyl, triazolyl, thiadiazolyl, thiadiazolyl, furazanyl, benzofurazanyl, benzothiophenyl, benzothiazolyl, benzoxazolyl, quinazolinyl, quinoxalinyl, naphthyridinyl, tetrahydrofuranyl, and furopyridinyl. The term “heteroaryloxy,” as used herein, refers to a monovalent radical of formula -OR, in which R is heteroaryl, as defined herein. The term “heterocyclyl,” as used herein, refers to saturated or unsaturated, non-aromatic, monocyclic, bicyclic, or multicyclic group containing 1, 2, 3, or 4 heteroatoms selected from N, O, S, B, and P (e.g., 1-4, 1- 3, or 1 or 2 heteroatoms selected from N, O, and S) as ring atoms, with the remaining ring atoms being carbon. The term “heterocyclyl” includes, e.g., monocyclic 3-to 12-membered rings, bicyclic 5- to 16- membered ring systems, multicyclic (e.g., tricyclic) 10- to 18-membered ring systems, which may include bridged ring systems when bicyclic or multicyclic. In some embodiments, a heterocyclyl group contains 3-16 ring atoms (i.e., 3- to 16-membered heterocyclyl), e.g., 3-12 ring atoms (i.e., 3- to 12-membered heterocyclyl) or 4-10 ring atoms (i.e., 4-to 10-membered heterocyclyl). Examples of saturated heterocyclyl groups include saturated 4- to 7-membered monocyclic groups containing 1 to 4 nitrogen atoms (e.g., pyrrolidinyl, imidazolidinyl, piperidinyl, pyrrolinyl, azetidinyl, piperazinyl, and pyrazolidinyl); saturated 4 to 6-membered monocyclic groups containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms (e.g., morpholinyl); saturated 3 ALXN-0780-PCT01-NP to 6-membered monocyclic groups containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms (e.g., thiazolidinyl). Examples of unsaturated, non-aromatic heterocyclyl radicals include but are not limited to, dihydrothienyl, dihydropyranyl, dihydrofuryl, and dihydrothiazolyl. Other examples of heterocyclyl radicals include, but are not limited to, pyrrolidinyl, imidazolidinyl, piperidinyl, pyrrolinyl, pyrazolidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, thiazolidinyl, dihydrothienyl, 2,3-dihydro-benzo[l,4]dioxanyl, indolinyl, isoindolinyl, dihydrobenzothienyl, dihydrobenzofuryl, isochromanyl, chromanyl, 1,2-dihydroquinolyl, 1,2,3,4- tetrahydro-isoquinolyl, 1,2,3,4-tetrahydro-quinolyl, 2,3,4,4a,9,9a-hexahydro-lH-3-aza-fluorenyl, 5,6,7-trihydro- l,2,4-triazolo[3,4-a]isoquinolyl, 3,4-dihydro-2H-benzo[1,4]oxazinyl, benzo[1,4]dioxanyl, 2,3-dihydro-1H-1λ- benzo[d]isothiazol-6-yl, dihydropyranyl, dihydrofuryl, and dihydrothiazolyl. “Bicyclic heterocyclyl” includes groups in which a saturated or unsaturated, non-aromatic ring containing 1, 2, 3, or 4 heteroatoms as ring atoms is fused with an aryl group (e.g., phenyl) or a cycloalkyl group. “Bicyclic heterocyclyl” also includes groups in which a heteroaryl group, as defined herein, is fused to a saturated or unsaturated, non-aromatic ring containing 0, 1, 2, 3, or 4 heteroatoms as ring atoms. The term “heterocyclyloxy,” as used herein, refers to a monovalent radical of formula -OR, in which R is heterocyclyl, as defined herein. The term “hydroxyalkyl,” as used herein, refers to a monovalent radical of formula -ROH, in which R is alkylene, as defined herein. The term “oxo,” as used herein, refers to a =O radial. The term “substituted”, as used herein, means that any one or more hydrogens on the designated atom or group is replaced with a moiety as defined herein or selected from an indicated group of moieties, provided that the designated atom's normal valence is not exceeded, and the resulting compound is stable. For example, when the substituent is oxo (i.e., =O), then two hydrogens on the atom are replaced. For example, a pyridyl group substituted by oxo is a pyridone. Combinations of substituents and / or variables are permissible only if such combinations result in stable compounds or useful synthetic intermediates. The phrase “optionally substituted X,” as used herein, is intended to be equivalent to “X, in which X is optionally substituted” (e.g., “alkyl, in which said alkyl is optionally substituted”). It is not intended to mean that the feature “X” (e.g., alkyl) per se is optional. The term “optionally substituted,” as used herein, refers to having 0, 1, or more substituents (e.g., 0-10 substituents, 0-5 substituents, or 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 substituents). Alkyl, alkylene, alkoxy, amino, carbocyclyl, aryl, aryloxy, heteroaryl, and heterocyclyl groups may be substituted with carbocyclyl (e.g., cycloalkyl); aryl; heteroaryl; heterocyclyl; halo; OR, in which R is H, alkyl, carbocyclyl (e.g., cycloalkyl), aryl, heteroaryl, or heterocyclyl; SR, in which R is H, alkyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl; CN; NO2; N3; NRR’; in which each of R and R’ is, independently, H, alkyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl; SO2R, in which R is H, alkyl, or aryl; SO2NRR’, in which each of R and R’ is, independently, H, alkyl, or aryl; SOR, in which R is H, alkyl, or aryl; or P(O)(OR)2, in which each R is, independently, H or alkyl. Amino, aryl, carbocyclyl, heteroaryl, and heterocyclyl groups may also be substituted with alkyl. Alkyl, alkylene, carbocyclyl, and heterocyclyl groups may also be substituted with oxo or =NR, in which R is H or alkyl. Alkyl and alkylene groups may also be substituted with spirocyclic carbocycle (e.g., spirocyclic cycloalkyl) or spirocyclic heterocyclyl. In some embodiments, a substituent is ALXN-0780-PCT01-NP further substituted with one or more substituents as described herein. For example, a C1 alkyl group, i.e., methyl, may be substituted with oxo to form a formyl group and further substituted with OH or NR2to form a carboxyl group or an amido group. The term “complement-mediated disorder,” as used herein, refers to a disorder in which the amount or activity of complement is such as to cause disorder in an individual. As used herein, a compound having “complement C1 esterase (C1s) inhibiting activity” refers to a compound exhibiting an IC50of less than 1 µM against as determined with a human complement C1s enzyme assay as described in Example 3 herein. The term “pharmaceutical composition,” as used herein, refers to one or more active compounds, formulated together with one or more pharmaceutically acceptable excipients. In some embodiments, a compound of the disclosure (e.g., is present in a unit dose amount appropriate for administration in a therapeutic regimen that shows a statistically significant probability of achieving a predetermined therapeutic effect when administered to a relevant population. In certain embodiments, pharmaceutical compositions may be specially formulated for administration in solid or liquid form, including those adapted for the following: oral administration, for example, drenches (aqueous or non-aqueous solutions or suspensions), tablets, or capsules; and parenteral administration, for example, by subcutaneous, intramuscular, or intravenous injection. As used herein, the term “pharmaceutically acceptable salt” represents those salts of the compounds described that are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and animals without undue toxicity, irritation, allergic response and the like and are commensurate with a reasonable benefit / risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, pharmaceutically acceptable salts are described in: Berge et al., J. Pharmaceutical Sciences 66:1- 19, 1977 and in Handbook of Pharmaceutical Salts: Properties, Selection, and Use, (Eds. P.H. Stahl and C.G. Wermuth), Wiley-VCH, 2008. These salts may be acid addition salts involving inorganic or organic acids. The salts can be prepared in situ during the final isolation and purification of the compounds described herein or separately by reacting the free base group with a suitable acid. The term “pharmaceutically acceptable excipient,” as used herein, refers to any inactive ingredient (for example, a vehicle capable of suspending or dissolving the active compound) that is biocompatible and suitable for administration to a subject. Typical excipients include, for example: antiadherents, antioxidants, binders, coatings, compression aids, disintegrants, dyes, emollients, emulsifiers, diluents, film formers or coatings, flavors, fragrances, glidants, lubricants, preservatives, printing inks, sorbents, suspending or dispersing agents, sweeteners, or waters of hydration. Those of ordinary skill in the art are familiar with a variety of agents and materials useful as excipients. The term “subject,” as used herein, can be a human, non-human primate, or other non-human mammal, such as but not limited to dog, cat, horse, cow, pig, goat, monkey, rat, mouse, and sheep. In preferred embodiments, the subject is a human. As used herein, and as well understood in the art, “to treat” a condition or “treatment” of various diseases and disorders is an approach for obtaining beneficial or desired results, such as clinical results. Beneficial or desired results can include, but are not limited to, alleviation of one or more symptoms or ALXN-0780-PCT01-NP conditions; diminishment of extent of disease, disorder, or condition; stabilizing (i.e., not worsening) of the state of disease, disorder, or condition; delay or slowing in the progress of the disease, disorder, or condition; amelioration or palliation of the disease, disorder, or condition; and remission (whether partial or total), whether detectable or undetectable. “Palliating” a disease, disorder, or condition means that the extent and / or undesirable clinical manifestations of the disease, disorder, or condition are lessened and / or the time course of the progression is slowed or lengthened, as compared to the extent or time course in the absence of treatment. A “therapeutically effective amount” or an “effective amount” of an active compound pharmaceutical composition of the present disclosure refers an amount effective, when administered to a subject, to provide a therapeutic benefit, such as an amelioration of symptoms or reduction or diminution of the disease itself. In one embodiment, a therapeutically effective amount is an amount sufficient to prevent a significant increase, or will significantly reduce, the detectable level of hemolysis in the patient’s blood, serum, or tissues. Detailed Description Active Compounds The present disclosure provides compounds and salts useful for the treatment of a disorder mediated by the complement cascade (e.g., a disorder mediated by C1s). In some embodiments, a compound of the present disclosure is a compound described by Formula (I): , or a pharmaceutically acceptable in which X1is O, S, C(Ra)2, or NRa, in which each Rais C6 haloalkyl, and C3-C6 cycloalkyl; X2is N or CRb, wherein Rbis absent or H; each of X3, X4, and X5is independently selected from NRcand C(Rc)2, wherein each Rcis independently selected from absent, H, halo, NH2, NH(C1-C6alkyl), N(C1-C6alkyl)2, and C1-C6alkyl, and only one of X3and X5can be NRcwhen X4is NRc; R6is H or halo; R7is H, halo, NH2, NH(C1-C6 alkyl), N(C1-C6 alkyl)2, C1-C6 alkyl, or C3-C6 cycloalkyl; and each is independently selected from a single bond and a double bond; each of R1, R1’, R2, and R2’ is independently selected from H, halo, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, and (C1-C6 alkoxy)(C1-C6 alkyl); R3is H; halo; C(O)Rd, wherein Rdis OH, O(C1-C6alkyl), NH2, NH(C1-C6alkyl), or N(C1-C6alkyl)2; OC(O)N(Re)2, in which each Reis independently selected from H and C1-C6alkyl; NRfC(O)N(Rf)2, in which each Rfis independently selected from H and C1-C6alkyl; C1-C6alkyl; C1-C6haloalkyl; (C1-C6alkoxy)(C1- C6alkyl); C6-C14 aryl; C3-C8 carbocyclyl; 5- to 10-membered heteroaryl containing 1, 2, or 3 ring atoms independently selected from N, O, and S; 4- to 10-membered heterocyclyl containing 1, 2, or 3 ring atoms ALXN-0780-PCT01-NP independently selected from N, O, and S; 6-membered heterocycloalkenyl containing 1, 2, or 3 ring atoms independently selected from N, O, and S; (4- to 10-membered heterocyclyl)oxy containing 1, 2, or 3 ring atoms independently selected from N, O, and S, or (5- to 9-membered heteroaryl)oxy containing 1, 2, or 3 ring atoms independently selected from N, O, and S; wherein R3is optionally substituted with one or more substituents independently selected from halo; C1-C6 alkyl; C1-C6 haloalkyl; (C1-C6 alkoxy)(C1-C6 alkyl); and 5- or 6-membered heterocycloalkyl containing 1, 2, or 3 ring atoms independently selected from N, O, and S; each of R4and R4’is independently selected from H, halo, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, and (C1-C6 alkoxy)(C1-C6 alkyl); R5is H or C1-C6 alkyl; R8is halo; R9is 5- to 10-membered heteroaryl containing 1, 2, 3, or 4 ring atoms independently selected from N, O, and S; X is C(Rg)2, O, or S; or each Rgis independently selected from H, halo, OH, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, and (C1-C6alkoxy)(C1-C6alkyl); or both Rg, together with the carbon atom to which they are attached, form C3-C8 spirocyclic cycloalkyl or 4- to 6-membered spirocyclic heterocycloalkyl containing 1 or 2 oxygen atoms; L is a bond or C1-C6 alkylene optionally substituted with one or more substituents independently selected from C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, (C1-C6alkoxy)(C1-C6alkyl), and oxo; and B is C1-C6alkyl; C6-C14aryl; C3-C14carbocyclyl; 5- to 14-membered heterocyclyl containing 1, 2, or 3 ring atoms independently selected from N, O, and S; or 5- to 10-membered heteroaryl containing 1, 2, or 3 ring atoms independently selected form N, O, and S; wherein B is optionally substituted with one or more substituents independently selected from halo; cyano; COORh, in which Rhis H or C1-C6alkyl; S(O)2(C1- C6alkyl); C1-C6alkyl; C1-C6haloalkyl; C1-C6alkoxy; C1-C6haloalkoxy; C6-C14aryl optionally substituted with one or more substituents independently selected from halo, COOH, SF5, S(O)2NH2, S(O)2(C1-C6alkyl), S(O)(NH)CH3, P(O)(OH)2, P(O)(OH)CH3, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C3-C6 carbocyclyl; C6-C14aryloxy; C3-C6cycloalkyl; C3-C6cycloalkyloxy; (C3-C8cycloalkyl)(C1-C6alkyl); (C6-C14aryl)(C1-C6alkyl); 5- or 6-membered heterocyclyl containing 1, 2, or 3 ring atoms independently selected from N, O, and S; and 5- or 6-membered heteroaryl containing 1, 2, or 3 ring atoms independently selected from N, O, and S and optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and C1-C6 haloalkyl. Exemplary Embodiments of Compounds of the Present Disclosure In some embodiments, the compound is of Formula (I’): , or a pharmaceutically acceptable In some embodiments, the compound is of Formula (I”): ALXN-0780-PCT01-NP , or a pharmaceutically acceptable In some In some embodiments, X3is N. In embodiments, X3is CNH2. In some embodiments, X5is CH. In some embodiments, X5is C(C1-C6alkyl). In some embodiments, X5is C(CH3). In some embodiments, X5is CNH2. In some embodiments, X4is N. In some embodiments, X1is S. In some embodiments, X1is O. In some embodiments, X1is NRa. In some embodiments, X1is NH. In some embodiments, X1is N(C1-C6alkyl). In some embodiments, X1is NCH3. In some embodiments, X1is NCH2CH3. In some embodiments, X1is N(C1-C6haloalkyl). In some embodiments, X1is NCHF2. In some embodiments, X1is N(C3-C6 cycloalkyl). In some embodiments, X1is N(cyclopropyl). . In some embodiments, X3is N. In some embodiments, X4is C some embodiments, X4is N. In some embodiments, X3is Rc C( )2. some some embodiments, X1is S. In some embodiments, X1is O. In some embodiments, X1is NRa. In some embodiments, X1is NH. In some embodiments, X1is N(C1-C6alkyl). In some embodiments, X1is NCH3. In some embodiments, X1is NCH2CH3. In some embodiments, X1is N(C1-C6 haloalkyl). In some embodiments, X1is NCHF2. In some embodiments, X1is N(C3-C6 cycloalkyl). In some embodiments, X1is N(cyclopropyl). In some embodiments, A . In some embodiments, X1is CRa. In some embodiments, X1is C(C1-C6 alkyl). In some is CCH3. In some embodiments, X1is CH. In some embodiments, X2is N. In some embodiments, X3is CH. In some embodiments, X4is CH. In some embodiments, R6is H. In some embodiments, R6is halo. In some embodiments, R6is F. In some embodiments, R7is H. In some embodiments, R7is NH2. In some embodiments, R7is halo. In some embodiments, R7is Cl. In some embodiments, R7is C1-C6 alkyl. In some embodiments, R7is methyl. In some embodiments, R7is C3-C6 cycloalkyl. In some embodiments, R7is cyclopropyl. ALXN-0780-PCT01-NP In some embodiments, A . In some embodiments, A embodiments, A . In some embodiments, A . In some embodiments, A is N . In some embodiments, A . In some embodiments, A . In some embodiments, A is . In some embodiments, A is . In some In some N embodiments, A isS. In some embodiments, A . In some embodiments, A is . In some embodiments, A is . In some embodiments, . In some embodiments, A . In some embodiments, A . In some embodiments, A is In some embodiments, . In some embodiments, A . In some In some embodiments, A is In some embodiments, . ALXN-0780-PCT01-NP In some embodiments, R1is H. In some embodiments, R1’is H. In some embodiments, R2is H. In some embodiments, R2is C1-C6alkyl. In some embodiments, R2is methyl. In some embodiments, R2’is H. In some embodiments, R2’is C1-C6alkyl. In some embodiments, R2’is methyl. In some embodiments, R3is H. In some embodiments, R3is C1-C6 alkyl. In some embodiments, R3is CH3. In some embodiments, R3is (CH2)3CH3. In some embodiments, R3is C1-C6 haloalkyl. In some embodiments, R3is CF3. In some embodiments, R3is C6-C14aryl optionally substituted with halo. In some embodiments, R3is phenyl optionally substituted with halo. In some embodiments, R3is . In some embodiments, R3is . In some embodiments, R3is C3-C8 carbocyclyl. In some embodiments, R3is C3-C8 cycloalkyl. In R3is cyclopropyl. In some embodiments, R3is 5- to 10-membered heteroaryl containing 1, 2, or 3 ring atoms independently selected from N, O, and S and optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, C1-C6 haloalkyl, (C1-C6 alkoxy)(C1-C6 alkyl), and 5- or 6- membered heterocycloalkyl containing 1, 2, or 3 ring atoms independently selected from N, O, and S. In some embodiments, R3is 5-membered heteroaryl containing 1 or 2 ring atoms independently selected from N, O, and S and optionally substituted with one or more substituents selected from halo, C1-C6alkyl, C1-C6 haloalkyl, (C1-C6 alkoxy)(C1-C6 alkyl), and 5- or 6-membered heterocycloalkyl containing 1 or 2 ring atoms independently selected from N and O. In some embodiments, R3. In some . In some embodiments, R3. In some embodiments, . In some embodiments, R3. In some embodiments, R3. In some embodiments, R3is In some . In some embodiments, R3. In some embodiments, R3is ALXN-0780-PCT01-NP . In some embodiments, R3is . In some embodiments, R3is . heteroaryl containing 1 or 2 ring atoms independently with one or more substituents selected from halo and C1- C6 alkyl. In some embodiments, R3. In some . In some . In some embodiments, R3. In R3is 6-membered 1 or 2 ring atoms independently selected from N and O and optionally substituted with C1-C6 alkyl. In some . In is independently selected from N and O. In some embodiments, R3. In some embodiments, X is C(Rg)2. In some In some embodiments, X is CHCH3. In some embodiments, both Rg, together with the carbon with which they are attached, form spirocyclic cyclopropyl. In some embodiments, X is O. In some embodiments, X is S. In some embodiments, R4is H. In some embodiments, R4is C1-C6alkyl. In some embodiments, R4is CH3. In some embodiments, R4is halo. In some embodiments, R4is F. In some embodiments, R4’is H. In some embodiments, R4’is C1-C6 alkyl. In some embodiments, R4’is CH3. In some embodiments, R4’is halo. In some embodiments, R4’is F. In some embodiments, R5is H. In some embodiments, R5is CH3. In some embodiments, L is a bond. In some embodiments, L is C1-C6alkylene. In some embodiments, L is -CH2-. In some embodiments, L is -(CH2)2-. In some embodiments, B is phenyl optionally substituted with one or more substituents independently selected from halo; cyano; COORh, in which Rhis C1-C6alkyl; S(O)2(C1-C6alkyl); C1-C6alkyl; C1-C6haloalkyl; C1-C6alkoxy; C1-C6haloalkoxy; phenyl optionally substituted with one or more halo; phenoxy; C3-C6cycloalkyl; C3-C6 cycloalkyloxy; 5- or 6-membered heterocyclyl containing 1 or 2 ring atoms independently ALXN-0780-PCT01-NP selected from N and O; and 5- or 6-membered heteroaryl containing 1, 2, or 3 ring atoms independently selected from N, O, and S and optionally substituted with one or more substituents selected from halo, C1-C6alkyl, and C1-C6 haloalkyl. In some embodiments, B is . In some embodiments, B is . In some embodiments, B . In some embodiments, B . In some embodiments, B . In some embodiments, B . In some embodiments, B . In some embodiments, B is . In some embodiments, B . In some embodiments, B is . In some . In some In ALXN-0780-PCT01-NP . . some . some O . In some embodiments, B is . In some . or more substituents selected from halo and C1-C6 alkoxy. In some embodiments, B . In some embodiments, B is . substituted with phenyl. In some embodiments, B is cyclohexyl. In some embodiments, B . In some embodiments, . In some . In some to 14-membered heterocyclyl including 1 or 2 oxygen atoms. In some embodiments, B . In some embodiments, B . In some embodiments, B is . atoms independently selected from N, O, and S; wherein B is optionally substituted with one or more substituents ALXN-0780-PCT01-NP independently selected from halo; C1-C6 alkyl; C1-C6 haloalkyl; C1-C6 alkoxy; phenyl optionally substituted with one or more substituents selected from halo, COOH, S(O)2NH2, S(O)2(C1-C6alkyl), C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, and C3-C6cycloalkyl; C3-C6carbocyclyl; (C3-C6cycloalkyl)(C1-C6alkyl); phenyl(C1-C6alkyl); 5- or 6-membered heterocyclyl containing 1 or 2 ring atoms independently selected from N and O; and 5- or 6-membered heteroaryl including 1 or 2 heteroatoms independently selected from N and O and optionally substituted with one or more halo. In some embodiments, B is 5-membered heteroaryl containing 1, 2, or 3 ring atoms independently selected from N, O, and S (e.g., furan, thiophene, oxazole, isooxazole, oxadiazole, thiazole, isothiazole, thiadiazole, pyrazole, or triazole) and optionally substituted with one or more substituents independently selected from halo; C1-C6alkyl; C1-C6haloalkyl; C1-C6alkoxy; phenyl optionally substituted with one or more substituents selected from halo, COOH, S(O)2NH2, S(O)2(C1-C6alkyl), C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, and C3-C6 cycloalkyl; C3-C6 carbocyclyl; (C3-C6 cycloalkyl)(C1-C6 alkyl); phenyl(C1-C6 alkyl); 5- or 6- membered heterocyclyl containing 1 or 2 ring atoms independently selected from N and O; and 5- or 6- membered heteroaryl containing 1 or 2 ring atoms independently selected from N and O and optionally substituted with one or more halo. In some embodiments, B is 5-membered heteroaryl containing 1, 2, or 3 ring atoms independently selected from N and O and substituted with phenyl optionally substituted with one or more substituents independently selected from halo and C1-C6haloalkoxy. B is In B embodiments, B is ALXN-0780-PCT01-NP In some embodiments, B . In some some In some embodiments, B . In some embodiments, B . In some In some embodiments, B N In some embodiments, B . In some embodiments, B . In some embodiments, B . In some embodiments, B . In some In some embodiments, B is . In some embodiments, B . In some In some embodiments, B is In some In some embodiments, B . In some In some embodiments, B . In some embodiments, B . In some In some embodiments, B is ALXN-0780-PCT01-NP . In some In some some embodiments, B is . In some embodiments, B is . In some embodiments, B . In some embodiments, B . In some embodiments, B is . In some . In some embodiments, B . In some embodiments, B . In some embodiments, B is . In some In some embodiments, B . In some embodiments, B . In some embodiments, B is . In some some In some embodiments, B is . In some embodiments, B . In some embodiments, B . In some embodiments, B . In some embodiments, B is ALXN-0780-PCT01-NP . In some In some some In some embodiments, B is In some In some some In some embodiments, B is In some . In some some In some embodiments, B is In some In some some In some embodiments, B is In some In some some In some embodiments, B is ALXN-0780-PCT01-NP In some In some some In some embodiments, B is In some In some some In some embodiments, B is In some In some some In some embodiments, B is In some some In some embodiments, B is . In some some In some embodiments, B is ALXN-0780-PCT01-NP NF selected from halo, C1-C6 alkoxy, and C3-C6 cycloalkyl. In some embodiments, B . In some . is independently selected from N, O, and S and optionally substituted with one or more halo. In some Cl is ALXN-0780-PCT01-NP acceptable salt thereof. In some embodiments, a compound of the disclosure is a compound having C1 esterase (C1s) inhibiting activity. Pharmaceutical Compositions A pharmaceutical composition of the disclosure contains one or more of the compounds disclosed herein (e.g., one or more of the compounds of Formulas (I), (I’), and (I”), and Table 1) as the therapeutic compound. In addition to a therapeutically effective amount of the compound, the pharmaceutical compositions also contain a pharmaceutically acceptable excipient, which can be formulated by methods known to those skilled in the art. In some embodiments, the pharmaceutical compositions for treating cancer contain one or more of the compounds disclosed herein (e.g., one or more of the compounds of Formulas (I), (I’), and (I”), and Table 1) may be formulated and / or administered with or without other therapeutics for a particular condition. Examples of such therapeutics (second therapeutic agents) are described herein. The compounds disclosed herein (e.g., the compounds of Formulas (I), (I’), and (I”), and Table 1) may be used in the form of free base or in the form of salts. All forms are within the scope of the disclosure. Exemplary routes of administration of the pharmaceutical compositions (or the compounds of the composition) include oral, sublingual, buccal, transdermal, intradermal, intramuscular, parenteral, intravenous, intra-arterial, intracranial, subcutaneous, intraorbital, intraventricular, intraspinal, intraperitoneal, intranasal, inhalation, and topical administration. In some embodiments, a compound of the present disclosure (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) is formulated for oral administration. Formulations for Oral Administration The pharmaceutical compositions of the present disclosure include those formulated for oral administration (“oral dosage forms”). Oral dosage forms can be, for example, in the form of tablets, capsules, a liquid solution or suspension, a powder, or liquid or solid crystals, which contain the active ingredient(s) in a mixture with non-toxic pharmaceutically acceptable excipients. These excipients may be, for example, inert diluents or fillers; granulating and disintegrating agents; binding agents; and lubricating agents, glidants, and ALXN-0780-PCT01-NP antiadhesives (e.g., magnesium stearate, zinc stearate, stearic acid, silicas, hydrogenated vegetable oils, or talc). Other pharmaceutically acceptable excipients can be colorants, flavoring agents, plasticizers, humectants, buffering agents, and the like. Pharmaceutical compositions for oral administration may also be presented as chewable tablets, as hard gelatin capsules where the active ingredient is mixed with an inert solid diluent, or as soft gelatin capsules where the active ingredient is mixed with water or an oil medium Powders, granulates, and pellets may be prepared using the ingredients mentioned above under tablets and capsules in a conventional manner using, e.g., a mixer, a fluid bed apparatus or a spray drying equipment. The liquid forms in which the compounds and compositions of the present disclosure can be incorporated for administration orally include aqueous solutions, suitably flavored syrups, aqueous or oil suspensions, and flavored emulsions with edible oils, as well as elixirs and similar pharmaceutical vehicles. Formulations for Parenteral Administration The pharmaceutical compositions of the present disclosure can be administered in a pharmaceutically acceptable parenteral (e.g., intravenous, intramuscular, subcutaneous or the like) formulation as described herein. The pharmaceutical composition may also be administered parenterally in dosage forms or formulations containing conventional, non-toxic pharmaceutically acceptable carriers and adjuvants. In particular, formulations suitable for parenteral administration include aqueous and non-aqueous sterile injection solutions which may contain antioxidants, buffers, bacteriostats and solutes which render the formulation isotonic with the blood of the intended recipient; and aqueous and non-aqueous sterile suspensions which may include suspending agents and thickening agents. For example, to prepare such a composition, the compounds of the present disclosure may be dissolved or suspended in a parenterally acceptable liquid vehicle. Among acceptable vehicles and solvents that may be employed are water; water adjusted to a suitable pH by addition of an appropriate amount of hydrochloric acid, sodium hydroxide, or a suitable buffer; 1,3-butanediol; Ringer’s solution; and isotonic sodium chloride solution. The aqueous formulation may also contain one or more preservatives. Additional information regarding parenteral formulations can be found, for example, in the United States Pharmacopeia-National Formulary (USP-NF), herein incorporated by reference in its entirety. The parenteral formulation can be any of the five general types of preparations identified by the USP- NF as suitable for parenteral administration: (1) “Drug Injection:” a liquid preparation that is a drug substance (e.g., a compound of the present disclosure), or a solution thereof; (2) “Drug for Injection:” the drug substance (e.g., a compound of the present disclosure) as a dry solid that will be combined with the appropriate sterile vehicle for parenteral administration as a drug injection; (3) “Drug Injectable Emulsion:” a liquid preparation of the drug substance (e.g., a compound of the present disclosure) that is dissolved or dispersed in a suitable emulsion medium; (4) “Drug Injectable Suspension:” a liquid preparation of the drug substance (e.g., a compound of the present disclosure) suspended in a suitable liquid medium; and ALXN-0780-PCT01-NP (5) “Drug for Injectable Suspension:” the drug substance (e.g., a compound of the present disclosure) as a dry solid that will be combined with the appropriate sterile vehicle for parenteral administration as a drug injectable suspension. Exemplary formulations for parenteral administration include solutions of the compound prepared in water suitably mixed with a surfactant, e.g., hydroxypropyl cellulose. Dispersions can also be prepared in glycerol, liquid polyethylene glycols, DMSO and mixtures thereof with or without alcohol, and in oils. Under ordinary conditions of storage and use, these preparations may contain a preservative to prevent the growth of microorganisms. Conventional procedures and ingredients for the selection and preparation of suitable formulations are described, for example, in Remington: The Science and Practice of Pharmacy, 23rdEd., Adejare, Ed., Academic Press (2020) and in The United States Pharmacopeia and National Formulary (USP- NF 2021 Issues 1-3), published in 2021. Formulations for parenteral administration may, for example, contain sterile water, saline, polyalkylene glycols (e.g., polyethylene glycol), oils of vegetable origin, or hydrogenated naphthalenes. Biocompatible, biodegradable lactide polymer, lactide / glycolide copolymer, or polyoxyethylene- polyoxypropylene copolymers may be used to control the release of the compounds. Other potentially useful parenteral delivery systems for compounds include ethylene-vinyl acetate copolymer particles, osmotic pumps, implantable infusion systems, and liposomes. Formulations for inhalation may contain, for example, lactose, or may be aqueous solutions containing, for example, polyoxyethylene-9-lauryl ether, glycocholate and deoxycholate, or may be oily solutions for administration in the form of nasal drops, or as a gel. The dosage of the compounds described herein (e.g., the compounds of Formulas (I), (I’), and (I”), and Table 1), and / or compositions including a compound described herein, can vary depending on many factors, such as the pharmacodynamic properties of the compound; the mode of administration; the age, health, and weight of the recipient; the nature and extent of the symptoms; the frequency of the treatment, and the type of concurrent treatment, if any; and the clearance rate of the compound in the subject to be treated. One of skill in the art can determine the appropriate dosage based on the above factors. In general, satisfactory results may be obtained when the compounds described herein are administered to a human at a daily dosage of, for example, between 0.05 mg and 3000 mg (measured as the solid form). For example, the dose range may be 10-1000 mg (e.g., 50-800 mg). Alternatively, the dosage amount can be calculated using the body weight of the patient. For example, the dose of a compound, or pharmaceutical composition thereof, administered to a patient may be 0.1-100 mg / kg. A dosage form containing a compound disclosed herein (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) can be administered, for example, once a day (QD), twice a day (BID), three times a day (TID), four times a day (QID), once every other day (Q2D), once every third day (Q3D), or any dosing schedule as needed, Uses of Active Compounds for Treatment of Selected Disorders In one aspect, an effective amount of an active compound described herein (e.g., any one of the compounds of Formulas (I), (I’), and (I”), and Table 1), or a pharmaceutically acceptable salt thereof) is used to treat a medical disorder which is an inflammatory or immune condition, a disorder mediated by the complement cascade (including a dysfunctional cascade) including a complement-related disorder or ALXN-0780-PCT01-NP alternative complement pathway-related disorder, a disorder or abnormality of a cell that adversely affects the ability of the cell to engage in or respond to normal complement activity, or an undesired complement- mediated response to a medical treatment, such as surgery or other medical procedure or a pharmaceutical or biopharmaceutical drug administration, a blood transfusion, or other allogenic tissue or fluid administration. In some embodiments, the disorder is an autoimmune disease. In some embodiments, the disorder is cancer. In some embodiments, the disorder is an infectious disease. In some embodiments, the disorder is an inflammatory disease. In some embodiments, the disorder is a hematological disease. In some embodiments, the disorder is an ischemia-reperfusion injury. In some embodiments, the disorder is an ocular disease. In some embodiments, the disorder is a renal disease. In some embodiments, the disorder is transplant rejection. In some embodiments, the disorder is antibody-mediated transplant rejection, e.g., acute antibody-mediated rejection. In some embodiments, the disorder is a vascular disease. In some embodiments, the disorder is a vasculitis disorder. In some embodiments, the disorder is a neurodegenerative disorder, e.g., a tauopathy. In some embodiments, the disorder is a medical disorder of the central nervous system (CNS) or peripheral nervous system disorders involving complement activation. In some embodiments, the disorder is an acquired brain or spinal cord injury. In some embodiments, the disorder is ischemic-reperfusion injury. In some embodiments, the disorder is stroke. In some embodiments, the disorder is traumatic brain injury (TBI). In some embodiments, the disorder is spinal cord injury (SCI). In some embodiments, the disorder is a neuroinflammatory disorder. In some embodiments, the neuroinflammatory disorder is cranial arteritis. In some embodiments, the neuroinflammatory disorder is giant cell arteritis. In some embodiments, the neuroinflammatory disorder is Holmes-Adie syndrome. In some embodiments, the neuroinflammatory disorder is inclusion body myositis (IBM). In some embodiments, the neuroinflammatory disorder is meningitis. In some embodiments, the neuroinflammatory disorder is a neurologic paraneoplastic syndrome, e.g., Lambert-Eaton myasthenic syndrome, stiff-person syndrome, encephalomyelitis (inflammation of the brain and spinal cord), myasthenia gravis, cerebellar degeneration, limbic and / or brainstem encephalitis, neuromyotonia, opsoclonus (involving eye movement), or sensory neuropathy. In some embodiments, the neuroinflammatory disorder is polymyositis. In some embodiments, the neuroinflammatory disorder is transverse myelitis. In some embodiments, the neuroinflammatory disorder is vasculitis, e.g., temporal arteritis. In some embodiments, the neuroinflammatory disorder is arachnoiditis. In some embodiments, the neuroinflammatory disorder is Kinsbourne syndrome. In some embodiments, the neuroinflammatory disorder is opsoclonus myoclonus syndrome (OMS). In some embodiments, the neuroinflammatory disorder is Saint Vitus Dance or Sydenham’s chorea (SD) disease. In some embodiments, the disorder is Alzheimer's disease (AD). AD is characterized by two hallmark pathologies; amyloid-β (Aβ) plaques and neurofibrillary tangles comprising hyperphosphorylated tau. Recent studies have implicated complement in AD pathogenesis, including genome-wide association studies identifying single nucleotide polymorphisms (SNPs) associated with risk of late-onset AD in genes encoding complement proteins clusterin (CLU) and CR1 (CR1). See Carpanini et al., Therapeutic Inhibition of the Complement System in Diseases of the Central Nervous System, Front. Immunol., 04 March 2019. ALXN-0780-PCT01-NP Biomarker studies have also identified complement proteins and activation products in plasma and / or CSF that distinguish AD from controls and predict risk of progression to AD. In some embodiments, the disorder is frontotemporal dementia. In some embodiments, the disorder is Pick's disease. In some embodiments, the disorder is sporadic frontotemporal dementia, e.g., frontotemporal dementia with Parkinsonism linked to chromosome 17. In some embodiments, progressive supranuclear palsy (PSP). In some embodiments, corticobasal degeneration (CBD). In some embodiments, the disorder is subacute sclerosing panencephalitis. In some embodiments, the disorder is amyotrophic lateral sclerosis (ALS). ALS is caused by progressive loss of upper and lower (α) motor neurons resulting in denervation of neuromuscular junctions in the peripheral nervous system, progressive muscle weakness, atrophy, spasticity, respiratory failure, and ultimately paralysis and death. Recent studies have shown increased C1q protein in motor cortex and spinal cord of ALS post-mortem tissue; C3 activation fragments and TCC in areas of pathology; C4d and TCC staining of degenerating neurons and glia in ALS motor cortex and spinal cord, and C5aR1 upregulation in areas of pathology. C3d and C4d have been found on oligodendroglia and degenerating neurites, surrounded by CR4-positive microglia, in spinal cord and motor cortex, and C1q, C3, and TCC have been shown to be present on motor endplates in intercostal muscles in ALS donors even early in the disease process. See Carpanini et al., Therapeutic Inhibition of the Complement System in Diseases of the Central Nervous System, Front. Immunol., 04 March 2019. In some embodiments, the disorder is Parkinson's disease (PD). PD is characterized by loss of dopaminergic neurons in the substantia nigra and deposits of the protein α-synuclein that form the pathological hallmarks of the disease, Lewy bodies. Patients present with resting tremor, bradykinesia, and rigidity. Complement activation has been associated with α-synuclein and Lewy bodies in Parkinson's disease; in vitro studies have demonstrated that the disease-associated splice variant α-synuclein 112, but not the full-length protein, cause activation of complement. In vivo, C3d, C4d, C7 and C9 localization in Lewy bodies has been reported. More recently, deposition of iC3b and C9 in Lewy bodies and melanized neurons has been reported, and iC3b immunoreactivity has been shown to be increased with normal ageing and was further elevated in PD vs. age-matched controls. Furthermore, correlation between the ratios of C3 / Aβ42 or FH / Aβ42 in CSF and severity of Parkinson's disease motor and cognitive symptoms has been shown. See Carpanini et al., Therapeutic Inhibition of the Complement System in Diseases of the Central Nervous System, Front. Immunol., 04 March 2019. In some embodiments, the subject to be treated suffers from Parkinson’s Disease with dementia (PDD). In some embodiments, the disorder is Huntington's disease (HD). HD is an autosomal dominant, inherited neurodegenerative disease characterized by progressive motor symptoms, psychiatric disturbances, and dementia. It is caused by expansion of a three-base-pair (CAG) repeat (39–121 repeats vs. normal range 8–39 repeats) in exon 1 of the HTT gene that translates into a polyglutamine tract at the N-terminus of the protein. This results in a polyglutamine length-dependent misfolding and accumulation of huntingtin protein in the striatum and cortex (layers 3, 5, and 6) followed by neuronal loss in these areas which spreads to the hippocampus. It has been shown that neurons, astrocytes, and myelin sheaths in the HD caudate and striatum were immunoreactive for C1q, C4, C3 and neo-epitopes in iC3b and TCC. Expression of mRNA ALXN-0780-PCT01-NP encoding early complement components C1q (c-chain), C1r, C3, and C4, complement regulators C1INH, Clusterin, MCP, DAF and CD59, and complement receptors C3a and C5a, have been shown to be upregulated in the HD striatum, see Carpanini et al., Therapeutic Inhibition of the Complement System in Diseases of the Central Nervous System, Front. Immunol., 04 March 2019. In some embodiments, the disorder is argyrophilic grain dementia. In some embodiments, the disorder is British type amyloid angiopathy. In some embodiments, the disorder is cerebral amyloid angiopathy. In some embodiments, the disorder is Creutzfeldt-Jakob disease. In some embodiments, the disorder is dementia pugilistica. In some embodiments, the disorder is diffuse neurofibrillary tangles with calcification. In some embodiments, the disorder is Down's syndrome. In some embodiments, the disorder is frontotemporal lobar degeneration. In some embodiments, the disorder is Gerstmann-Straussler-Scheinker disease. In some embodiments, the disorder is Hallervorden-Spatz disease. In some embodiments, the disorder is inclusion body myositis. In some embodiments, the disorder is multiple system atrophy (MSA). In some embodiments, the disorder is myotonic dystrophy. In some embodiments, the disorder is Niemann-Pick disease type C. In some embodiments, the disorder is non-Guamanian motor neuron disease with neurofibrillary tangles. In some embodiments, the disorder is postencephalitic parkinsonism. In some embodiments, the disorder is prion protein cerebral amyloid angiopathy. In some embodiments, the disorder is progressive subcortical gliosis. In some embodiments, the disorder is progressive supranuclear palsy. In some embodiments, the disorder is subacute sclerosing panencephalitis. In some embodiments, the disorder is Tangle only dementia. In some embodiments, the disorder is multi-infarct dementia. In some embodiments, the disorder is ischemic stroke. In some embodiments, the disorder is chronic traumatic encephalopathy (CTE). In some embodiments, the disorder is a hereditary motor and sensory neuropathy (HMSN). In some embodiments, the HMSN is Charcot-Marie-Tooth (CMT) disease. In some embodiments, the HSMN is Charcot–Marie–Tooth disease type 1A or type 1B. In some embodiments, the HSMN is Charcot–Marie– Tooth disease type 2. In some embodiments, the HSMN is Dejerine–Sottas disease (Charcot–Marie–Tooth type 3). In some embodiments, the HSMN is Refsum disease. In some embodiments, the HSMN is Charcot– Marie–Tooth with pyramidal features. In some embodiments, the HSMN is Charcot–Marie–Tooth type 6. In some embodiments, the HSMN is HMSN+retinitis pigmentosa. In some embodiments, the disorder is Churg-Strauss syndrome. In some embodiments, the disorder is peripheral artery disease (PAD). In some embodiments, the disorder is myasthenia gravis, e.g., myasthenia gravis with CNS involvement. In some embodiments, the disorder is dementia with Lewy bodies. In some embodiments, the disorder is prion disease. In some embodiments, the disorder is Behcet's Disease. In some embodiments, the disorder is congenital myasthenia. In some embodiments, the disorder is subacute sclerosing panencephalitis (SSPE). In some embodiments, the disorder is a demyelinating disease. In some embodiments, the disorder is demyelinating myelinoclastic disease. In some embodiments, the disorder is demyelinating leukodystrophic disease. In some embodiments, the demyelinating myelinoclastic disease is multiple sclerosis (MS). Multiple sclerosis (MS) is the most common cause of neurological disability in young adults in northern European- ALXN-0780-PCT01-NP Caucasian populations, with an approximate lifetime risk of one in 400. C3 has been shown to be deposited in the brains of MS patients. T-cell clone (TCC) has been shown to be in association with capillary endothelial cells, predominantly within plaques and adjacent white matter. Localization of C activation to areas of active myelin destruction has also been shown, with TCC deposited exclusively in such areas. C3d has been shown to be deposited in association with short segments of disrupted myelin in plaques with low-grade active demyelination and provides evidence for a C contribution to disease progression as well as acute inflammation. See Ingram et al., Complement in multiple sclerosis: its role in disease and potential as a biomarker. Clin Exp Immunol.2009 Feb;155(2):128-39. In some embodiments, the demyelinating myelinoclastic disease is neuromyelitis optica (NMO). Neuromyelitis optica (NMO) is an inflammatory demyelinating disease affecting predominantly the optic nerves and spinal cord. Traditionally seen as a variant of MS, it has been redefined recently according to new criteria using a combination of phenotypic subtyping along with a newly developed biomarker of disease, NMO-immunoglobulin G (IgG) (reported sensitivity of 58–76% and specificity of 85–99% for NMO). NMO patients have higher levels of C3a and anti-C1q antibodies than healthy controls. C3a levels correlated with disease activity, neurological disability and aquaporin-4 IgG. Nytrova et al. J Neuroimmunol.2014 Sep 15;274(1-2):185-91. In some embodiments, the demyelinating myelinoclastic disease is idiopathic inflammatory demyelinating diseases (IIDD). In some embodiments, the demyelinating myelinoclastic disease is anti- NMDA receptor encephalitis. In some embodiments, the demyelinating myelinoclastic disease is acute disseminated encephalomyelitis. In some embodiments, the demyelinating myelinoclastic disease is anti- MOG autoimmune encephalomyelitis. In some embodiments, the demyelinating myelinoclastic disease is chronic relapsing inflammatory optic neuritis (CRION). In some embodiments, the demyelinating myelinoclastic disease is acute disseminated encephalomyelitis (ADEM). In some embodiments, the demyelinating myelinoclastic disease is immune-mediated encephalomyelitis. In some embodiments, the demyelinating myelinoclastic disease is progressive multifocal leukoencephalopathy (PML). In some embodiments, the demyelinating myelinoclastic disease is McDonalds-positive multiple sclerosis. In some embodiments, the demyelinating myelinoclastic disease is acute hemorrhagic leukoencephalitis. In some embodiments, the demyelinating myelinoclastic disease is Rasmussen's Encephalitis. In some embodiments, the demyelinating myelinoclastic disease is Marburg multiple sclerosis. In some embodiments, the demyelinating myelinoclastic disease is pseudotumefactive or tumefactive multiple sclerosis. In some embodiments, the demyelinating myelinoclastic disease is Balo concentric sclerosis. In some embodiments, the demyelinating myelinoclastic disease is diffuse myelinoclastic sclerosis. In some embodiments, the demyelinating myelinoclastic disease is solitary sclerosis. In some embodiments, the demyelinating myelinoclastic disease is multiple sclerosis with cavitary lesions. In some embodiments, the demyelinating myelinoclastic disease is myelocortical multiple sclerosis (MCMS). In some embodiments, the demyelinating myelinoclastic disease is atypical optic-spinal multiple sclerosis. In some embodiments, the demyelinating myelinoclastic disease is pure spinal multiple sclerosis. In some embodiments, the demyelinating myelinoclastic disease is HLA DRB3*02:02 multiple sclerosis. In some embodiments, the demyelinating myelinoclastic disease is autoimmune GFAP astrocytopathy. In some embodiments, the demyelinating ALXN-0780-PCT01-NP myelinoclastic disease is chronic inflammatory demyelinating polyneuropathy (CIDP). In some embodiments, the demyelinating myelinoclastic disease is Guillain–Barré syndrome (acute or chronic). In some embodiments, the demyelinating myelinoclastic disease is progressive inflammatory neuropathy. In some embodiments, the demyelinating myelinoclastic disease is Lewis-Sumner Syndrome. In some embodiments, the demyelinating myelinoclastic disease is combined central and peripheral demyelination (CCPD). In some embodiments, the demyelinating myelinoclastic disease is Bickerstaff brainstem encephalitis. In some embodiments, the demyelinating myelinoclastic disease is Fisher syndrome. In some embodiments, the demyelinating myelinoclastic disease is trigeminal neuralgia. In some embodiments, the demyelinating myelinoclastic disease is NMDAR anti-NMDA receptor encephalitis. In some embodiments, the demyelinating myelinoclastic disease is primary progressive MS (PPMS). In some embodiments, the demyelinating myelinoclastic disease is OPA1 variant multiple sclerosis. In some embodiments, the demyelinating myelinoclastic disease is KIR4.1 multiple sclerosis. In some embodiments, the demyelinating myelinoclastic disease is aquaporin-related multiple sclerosis. In some embodiments, the demyelinating myelinoclastic disease is chronic cerebrospinal venous insufficiency (CCSVI or CCVI). In some embodiments, the demyelinating myelinoclastic disease is diffuse sclerosis. In some embodiments, the demyelinating myelinoclastic disease is Schilder's disease. In certain aspects, the disorder to be treated is a demyelinating leukodystrophic disease. In some embodiments, the demyelinating leukodystrophic disease is myelitis. In some embodiments, the demyelinating leukodystrophic disease is central pontine myelinolysis (CPM). In some embodiments, the demyelinating leukodystrophic disease is extrapontine myelinolysis. In some embodiments, the demyelinating leukodystrophic disease is tabes dorsalis. In some embodiments, the demyelinating leukodystrophic disease is progressive multifocal leukoencephalopathy. In some embodiments, the demyelinating leukodystrophic disease is leukoencephalopathy with vanishing white matter. In some embodiments, the demyelinating leukodystrophic disease is leukoencephalopathy with neuroaxonal spheroids. In some embodiments, the demyelinating leukodystrophic disease is reversible posterior leukoencephalopathy syndrome. In some embodiments, the demyelinating leukodystrophic disease is megalencephalic leukoencephalopathy with subcortical cysts. In some embodiments, the demyelinating leukodystrophic disease is megalencephalic leukoencephalopathy with subcortical cysts 1. In some embodiments, the demyelinating leukodystrophic disease is hypertensive leukoencephalopathy. In some embodiments, the demyelinating leukodystrophic disease is metachromatic leukodystrophy. In some embodiments, the demyelinating leukodystrophic disease is Krabbe disease. In some embodiments, the demyelinating leukodystrophic disease is Canavan disease. In some embodiments, the demyelinating leukodystrophic disease is X-linked adrenoleukodystrophy. In some embodiments, the demyelinating leukodystrophic disease is Alexander disease. In some embodiments, the demyelinating leukodystrophic disease is cerebrotendinous xanthomatosis. In some embodiments, the demyelinating leukodystrophic disease is Pelizaeus–Merzbacher disease. In some embodiments, the demyelinating leukodystrophic disease is Refsum disease. ALXN-0780-PCT01-NP In some embodiments, an effective amount of an active compound described herein, or a pharmaceutically acceptable salt thereof, is used to treat Buerger's disease, also known as thromboangiitis obliterans. In some embodiments, an effective amount of an active compound described herein, or a pharmaceutically acceptable salt thereof, is used to treat giant cell arteritis. In some embodiments, an effective amount of an active compound described herein, or a pharmaceutically acceptable salt thereof, is used to treat Raynaud's disease. In certain aspects, the disorder to be treated is a demyelinating disease of the peripheral nervous system. In some embodiments, the demyelinating disease of the peripheral nervous system is anti-MAG peripheral neuropathy. In some embodiments, the demyelinating disease of the peripheral nervous system is hereditary neuropathy with liability to pressure palsy. In some embodiments, the demyelinating disease of the peripheral nervous system is a copper deficiency-associated condition (e.g., peripheral neuropathy, myelopathy, or rarely optic neuropathy). In some embodiments, an effective amount of an active compound described herein, or a pharmaceutically acceptable salt thereof, is used to treat transverse myelitis. In certain aspects, the disorder to be treated is a peripheral neuropathy. In some embodiments, the peripheral neuropathy is a mononeuropathy. In some embodiments, the neuropathy is a polyneuropathy. In some embodiments, the polyneuropathy is distal axonopathy, diabetic neuropathy, a demyelinating polyneuropathy, small fiber peripheral neuropathy, mononeuritis multiplex, polyneuritis multiplex, autonomic neuropathy, or neuritis. In some embodiments, an effective amount of an active compound described herein, or a pharmaceutically acceptable salt thereof, is used to treat multifocal motor neuropathy. In some embodiments, an effective amount of an active compound described herein, or a pharmaceutically acceptable salt thereof, is used to treat an autoimmune vascular disease. In some embodiments, the autoimmune vascular disease is vasculitis. In some embodiments, the vasculitis includes, but is not limited to, autoimmune inflammatory vasculitis, Cutaneous small-vessel vasculitis, Granulomatosis with polyangiitis , Eosinophilic granulomatosis with polyangiitis, Behçet's disease, Kawasaki disease, Buerger's disease, and "Limited" granulomatosis with polyangiitis vasculitis. In some embodiments, an active compound (e.g., any one of the compounds of Formulas (I), (I’), and (I”), and Table 1) or its salt or composition as described herein is used to treat an arteritis. In some embodiments, the arteritis is giant cell arteritis. In some embodiments, the arteritis is Takayasu arteritis. In some embodiments, the arteritis is temporal arteritis. In some embodiments, the arteritis is polyarteritis nodosa. In some embodiments, a method for the treatment of a glomerulonephritis is provided. In some embodiment, the glomerulonephritis is membranoproliferative glomerulonephritis (MPGN). In some embodiments, the MPGN is MPGN Type I. In some embodiments, the MPGN is MPGN Type II. In some embodiments, the MPGN is MPGN Type III. In some embodiments, the MPGN is C3 glomerulonephritis (C3G). In some embodiments, the MPGN is dense deposit disease (DDD). In some embodiments, the MPGN is a C4 deposition disorder. ALXN-0780-PCT01-NP In some embodiments, the glomerulonephritis is IC-MPGN. In some embodiments, the glomerulonephritis is a membranous glomerulonephritis. In some embodiments, the glomerulonephritis is IgA nephropathy. In some embodiments, the glomerulonephritis is post-infectious glomerulonephritis. In some embodiments, the glomerulonephritis is a rapidly progressive glomerulonephritis, for example Type I (Goodpasture syndrome), Type II, or Type III rapidly progressive glomerulonephritis. In some embodiments, a method for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) is provided that includes the administration of an effective amount of a compound disclosed herein (e.g., any one of the compounds of Formulas (I), (I’), and (I”), and Table 1) or a pharmaceutically acceptable salt thereof to a subject, optionally in a pharmaceutically acceptable composition. In some embodiments, a method for the treatment of hereditary angioedema (HAE) is provided that includes the administration of an effective amount of a compound disclosed herein (e.g., any one of the compounds of Formulas (I), (I’), and (I”), and Table 1) or a pharmaceutically acceptable salt thereof to a subject, optionally in a pharmaceutically acceptable composition. Mutations in the SERPING1 gene cause hereditary angioedema type I and type II. Hereditary angioedema is a disorder characterized by recurrent episodes of severe swelling (angioedema). The most common areas of the body to develop swelling are the limbs, face, intestinal tract, and airway. The SERPING1 gene provides instructions for making the C1 inhibitor protein, which is important for controlling inflammation. C1 inhibitor blocks the activity of certain proteins that promote inflammation. Mutations that cause hereditary angioedema type I lead to reduced levels of C1 inhibitor in the blood, while mutations that cause type II result in the production of a C1 inhibitor that functions abnormally. Without the proper levels of functional C1 inhibitor, excessive amounts of a protein fragment (peptide) called bradykinin are generated. Bradykinin promotes inflammation by increasing the leakage of fluid through the walls of blood vessels into body tissues. Excessive accumulation of fluids in body tissues causes the episodes of swelling seen in individuals with hereditary angioedema type I and type II. In some embodiments, a method for the treatment of cold agglutinin disease (CAD) is provided that includes the administration of an effective amount of a compound disclosed herein (e.g., any one of the compounds of Formulas (I), (I’), and (I”), and Table 1) or a pharmaceutically acceptable salt thereof to a subject, optionally in a pharmaceutically acceptable composition. CAD is a rare autoimmune hemolytic condition with potentially serious acute and chronic consequences that are driven by C1 activation of the classical complement pathway. In some embodiments, a method for the treatment of atypical hemolytic uremic syndrome (aHUS) is provided that includes the administration of an effective amount of a compound disclosed herein (e.g., any one of the compounds of Formulas (I), (I’), and (I”), and Table 1) or a pharmaceutically acceptable salt thereof to a subject, optionally in a pharmaceutically acceptable composition. Atypical hemolytic-uremic syndrome is a disease that primarily affects kidney function. Atypical hemolytic uremic syndrome, which can occur at any age, causes abnormal blood clots (thrombi) to form in small blood vessels in the kidneys. These clots can cause serious medical problems if they restrict or block blood flow. Atypical hemolytic-uremic syndrome is characterized by three major features related to abnormal clotting: hemolytic anemia, thrombocytopenia, and kidney failure. ALXN-0780-PCT01-NP In another embodiment, a method for the treatment of wet or dry age-related macular degeneration (AMD) in a subject is provided that includes the administration of an effective amount of a compound disclosed herein (e.g., any one of the compounds of Formulas (I), (I’), and (I”), and Table 1) or a pharmaceutically acceptable salt thereof to a subject, optionally in a pharmaceutically acceptable composition. In another embodiment, a method for the treatment of rheumatoid arthritis in a subject is provided that includes the administration of an effective amount of a compound disclosed herein (e.g., any one of the compounds of Formulas (I), (I’), and (I”), and Table 1) or a pharmaceutically acceptable salt thereof to a subject, optionally in a pharmaceutically acceptable composition. In another embodiment, a method for the treatment of multiple sclerosis in a subject is provided that includes the administration of an effective amount of a compound disclosed herein (e.g., any one of the compounds of Formulas (I), (I’), and (I”), and Table 1) or a pharmaceutically acceptable salt thereof to a subject, optionally in a pharmaceutically acceptable composition. The active compounds or pharmaceutically acceptable salts thereof disclosed herein, are also useful for administration in combination (in the same or a different dosage form) or alternation with a second pharmaceutical agent for use in ameliorating or reducing a side effect of the second pharmaceutical agent. For example, in some embodiments, the active compound may be used in combination with an adoptive cell-transfer therapy to reduce an inflammatory response associated with such therapy, for example, a cytokine mediated response such as cytokine response syndrome. In some embodiments, the adoptive cell-transfer therapy is a chimeric antigen receptor T-Cell (CAR T), or a dendritic cell used to treat a hematologic or solid tumor, for example, a B-cell related hematologic cancer. In some embodiments, the hematologic or solid tumor is acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), non-Hodgkin’s lymphoma, chronic lymphocytic leukemia (CLL), pancreatic cancer, glioblastoma, or a cancer that expresses CD19. In some embodiments, the adoptive cell-transfer therapy is a non-engineered T-cell therapy, in which the T-cells have been activated and / or expanded to one or more viral or tumor antigens. In some embodiments, the associated inflammatory response is a cytokine mediated response. In some embodiments, the second pharmaceutical agent is a cell that has been transformed to express a protein, in which the protein in the subject is mutated or otherwise has impaired function. In some embodiments, the transformed cell includes a CRISPR gene. Another embodiment is provided that includes the administration of an effective amount of an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable composition to a subject to treat an ocular, pulmonary, gastrointestinal, or other disorder. In other embodiments of the disclosure, an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) provided herein can be used to treat or prevent a disorder in a subject mediated by complement. As examples, the disclosure includes methods to treat or prevent complement associated disorders that are induced by antibody-antigen interactions, a component of an immune or autoimmune disorder or by ischemic injury. The disclosure also provides methods to decrease inflammation or an immune ALXN-0780-PCT01-NP response, including an autoimmune response, where mediated or affected by the classical complement pathway. In some embodiments, the disorder is selected from fatty liver and conditions stemming from fatty liver, such as nonalcoholic steatohepatitis (NASH), liver inflammation, cirrhosis, and liver failure. In some embodiments of the present disclosure, a method is provided for treating fatty liver disease in a subject by administering an effective amount of an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein. In another embodiment, an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein is used to modulate an immune response prior to or during surgery or other medical procedure. One non-limiting example is use in connection with acute or chronic graft versus subject disease, which is a common complication as a result of organ transplantation, allogeneic tissue transplant, and can also occur as a result of a blood transfusion. In some embodiments, the present disclosure provides a method of treating dermatomyositis by administering to a subject in need thereof an effective amount of an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein. In some embodiments, the present disclosure provides a method of treating amyotrophic lateral sclerosis by administering to a subject in need thereof an effective amount of an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein. In some embodiments, the present disclosure provides a method of treating abdominal aortic aneurysm, hemodialysis complications, hemolytic anemia, or hemodialysis by administering to a subject in need thereof an effective amount of an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein. In another embodiment, a method is provided for the treatment or prevention of cytokine or inflammatory reactions in response to the administration of pharmaceutical or biotherapeutic (e.g., CAR T-cell therapy or monoclonal antibody therapy) in a subject by administering an effective amount of an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein. Various types of cytokine or inflammatory reactions may occur in response to a number of factors, such as the administrations of biotherapeutics. In some embodiments, the cytokine or inflammatory reaction is cytokine release syndrome. In some embodiments, the cytokine or inflammatory reaction is tumor lysis syndrome (which also leads to cytokine release). Symptoms of cytokine release syndrome range from fever, headache, and skin rashes to bronchospasm, hypotension, and even cardiac arrest. Severe cytokine release syndrome is described as a cytokine storm and can be fatal. Fatal cytokine storms have been observed in response to infusion with several monoclonal antibody therapeutics. See, Abramowicz D, et al. “Release of tumor necrosis factor, interleukin-2, and gamma- interferon in serum after injection of OKT3 monoclonal antibody in kidney transplant recipients” Transplantation (1989) 47(4):606-8; Chatenoud L, et al. “In vivo cell activation following OKT3 administration. Systemic cytokine release and modulation by corticosteroids” Transplantation (1990) 49(4):697-702; and Lim ALXN-0780-PCT01-NP LC, Koh LP, and Tan P. “Fatal cytokine release syndrome with chimeric anti-CD20 monoclonal antibody rituximab in a 71-year-old patient with chronic lymphocytic leukemia” J. Clin Oncol. (1999) 17(6):1962-3. Also contemplated herein, is the use of an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein to mediate an adverse immune response in patients receiving bi-specific T-cell engagers (BiTE). A bi-specific T-cell engager directs T-cells to target and bind with a specific antigen on the surface of a cancer cell. For example, Blinatumomab (Amgen), a BiTE has recently been approved as a second line therapy in Philadelphia chromosome-negative relapsed or refractory acute lymphoblastic leukemia. Blinatumomab is given by continuous intravenous infusion in 4-week cycles. The use of BiTE agents has been associated with adverse immune responses, including cytokine release syndrome. The most significantly elevated cytokines in the CRS associated with ACT include IL-10, IL-6, and IFN-γ (Klinger et al., Immunopharmacologic response of patients with B-lineage acute lymphoblastic leukemia to continuous infusion of T cell-engaging CD19 / CD3-bispecific BiTE antibody blinatumomab. Blood (2012) 119:6226–6233). In another embodiment, the disorder is episcleritis, idiopathic episcleritis, anterior episcleritis, or posterior episcleritis. In some embodiments, the disorder is idiopathic anterior uveitis, HLA-B27 related uveitis, herpetic keratouveitis, Posner Schlossman syndrome, Fuch’s heterochromic iridocyclitis, or cytomegalovirus anterior uveitis. In some embodiments, the present disclosure provides a method of treating an IC-MPGN by administering to a subject in need thereof an effective amount of an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein. In some embodiments, the present disclosure provides a method of treating a paroxysmal nocturnal hemoglobinuria (PNH) by administering to a subject in need thereof an effective amount of an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein. In some embodiments, the present disclosure provides a method of treating a hereditary angioedema (HAE) by administering to a subject in need thereof an effective amount of an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein. In some embodiments, the present disclosure provides a method of treating cold agglutinin disease (CAD) by administering to a subject in need thereof an effective amount of an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein. In some embodiments, the present disclosure provides a method of treating atypical hemolytic syndrome (aHUS) by administering to a subject in need thereof an effective amount of an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein. In some embodiments, the present disclosure provides a method of treating age-related macular degeneration (AMD) by administering to a subject in need thereof an effective amount of an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein. In some embodiments, the present disclosure provides a method of treating rheumatoid arthritis by administering to a subject in need thereof an effective amount of an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein. ALXN-0780-PCT01-NP In some embodiments, the present disclosure provides a method of treating multiple sclerosis by administering to a subject in need thereof an effective amount of an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein. In some embodiments, the present disclosure provides a method of treating myasthenia gravis by administering to a subject in need thereof an effective amount of an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein. In some embodiments, the present disclosure provides a method of treating atypical hemolytic uremic syndrome (aHUS) by administering to a subject in need thereof an effective amount of an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein. In another embodiment, the present disclosure provides a method of treating a disorder as described below by administering to a subject in need thereof an effective amount of an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein, including: vitritis, sarcoidosis, syphilis, tuberculosis, or Lyme disease; retinal vasculitis, Eales disease, tuberculosis, syphilis, or toxoplasmosis; neuroretinitis, viral retinitis, or acute retinal necrosis; varicella zoster virus, herpes simplex virus, cytomegalovirus, Epstein-Barr virus, lichen planus, or Dengue-associated disease (e.g., hemorrhagic Dengue Fever); Masquerade syndrome, contact dermatitis, trauma induced inflammation, UVB induced inflammation, eczema, granuloma annulare, or acne. In an additional embodiment, the disorder is selected from: acute myocardial infarction, aneurysm, cardiopulmonary bypass, dilated cardiomyopathy, complement activation during cardiopulmonary bypass operations, coronary artery disease, restenosis following stent placement, or percutaneous transluminal coronary angioplasty (PTCA); antibody-mediated transplant rejection, anaphylactic shock, anaphylaxis, allogenic transplant, humoral and vascular transplant rejection, graft dysfunction, graft-versus-subject disease, Graves' disease, adverse drug reactions, or chronic graft vasculopathy; allergic bronchopulmonary aspergillosis, allergic neuritis, drug allergy, radiation- induced lung injury, eosinophilic pneumonia, radiographic contrast media allergy, bronchiolitis obliterans, or interstitial pneumonia; parkinsonism-dementia complex, sporadic frontotemporal dementia, frontotemporal dementia with Parkinsonism linked to chromosome 17, frontotemporal lobar degeneration, tangle only dementia, cerebral amyloid angiopathy, cerebrovascular disorder, certain forms of frontotemporal dementia, argyrophilic grain dementia, dementia pugilistica, dementia with Lewy Bodies (DLB), or multi-infarct dementia; Creutzfeldt-Jakob disease, multifocal motor neuropathy (MMN), prion protein cerebral amyloid angiopathy, polymyositis, postencephalitic parkinsonism, subacute sclerosing panencephalitis, non-Guamanian motor neuron disease with neurofibrillary tangles, neural regeneration, and diffuse neurofibrillary tangles with calcification. In some embodiments, the disorder is selected from: atopic dermatitis, dermatitis, dermatomyositis bullous pemphigoid, scleroderma, sclerodermatomyositis, psoriatic arthritis, pemphigus vulgaris, Discoid lupus erythematosus, cutaneous lupus, chilblain lupus erythematosus, or lupus erythematosus-lichen planus overlap syndrome; cryoglobulinemic vasculitis, mesenteric / enteric vascular disorder, peripheral vascular disorder, antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV), IL-2 induced vascular leakage syndrome, immune complex vasculitis, angioedema, low platelets (HELLP) syndrome, sickle cell disease, platelet refractoriness, red cell casts, or typical or infectious hemolytic uremic syndrome (tHUS); ALXN-0780-PCT01-NP hematuria, hemorrhagic shock, drug-induced thrombocytopenia, autoimmune hemolytic anemia (AIHA), azotemia, blood vessel and / or lymph vessel inflammation, rotational atherectomy, or delayed hemolytic transfusion reaction; British type amyloid angiopathy, Buerger's disease, bullous pemphigoid, C1q nephropathy, cancer, and catastrophic antiphospholipid syndrome. In some embodiments, the disorder is autoimmune hemolytic anemia, e.g., warm autoimmune hemolytic anemia. In another embodiment, the disorder is selected from: wet (exudative) AMD, dry (non-exudative) AMD, chorioretinal degeneration, choroidal neovascularization (CNV), choroiditis, loss of RPE function, loss of vision (including loss of visual acuity or visual field), loss of vision from AMD, retinal damage in response to light exposure, retinal degeneration, retinal detachment, retinal dysfunction, retinal neovascularization (RNV), retinopathy of prematurity, pathological myopia, or RPE degeneration; pseudophakic bullous keratopathy, symptomatic macular degeneration related disorder, optic nerve degeneration, photoreceptor degeneration, cone degeneration, loss of photoreceptor cells, pars planitis, scleritis, proliferative vitreoretinopathy, or formation of ocular drusen; chronic urticaria, Churg-Strauss syndrome, cold agglutinin disease (CAD), corticobasal degeneration (CBD), cryoglobulinemia, cyclitis, damage of the Bruch's membrane, Degos disease, diabetic angiopathy, elevated liver enzymes, endotoxemia, epidermolysis bullosa, or epidermolysis bullosa acquisita; essential mixed cryoglobulinemia, excessive blood urea nitrogen-BUN, focal segmental glomerulosclerosis, Gerstmann-Straussler-Scheinker disease, giant cell arteritis, gout, Hallervorden-Spatz disease, Hashimoto's thyroiditis, Henoch-Schonlein purpura nephritis, or abnormal urinary sediments; hepatitis, hepatitis A, hepatitis B, hepatitis C or human immunodeficiency virus (HIV), a viral infection more generally, for example selected from Flaviviridae, Retroviruses, Coronaviridae, Poxviridae, Adenoviridae, Herpesviridae, Caliciviridae, Reoviridae, Picornaviridae, Togaviridae, Orthomyxoviridae, Rhabdoviridae, or Hepadnaviridae; Neisseria meningitidis, shiga toxin E. coli-related hemolytic uremic syndrome (STEC-HUS), hemolytic uremic syndrome (HUS); Streptococcus, and poststreptococcal glomerulonephritis. In a further embodiment, the disorder is selected from: hyperlipidemia, hypertension, hypoalbuminemia, hypovolemic shock, hypocomplementemic urticarial vasculitis syndrome, hypophosphastasis, hypovolemic shock, idiopathic pneumonia syndrome, or idiopathic pulmonary fibrosis; inclusion body myositis, intestinal ischemia, iridocyclitis, iritis, juvenile chronic arthritis, Kawasaki's disease (arteritis), or lipiduria; membranoproliferative glomerulonephritis (MPGN) I, microscopic polyangiitis, mixed cryoglobulinemia, molybdenum cofactor deficiency (MoCD) type A, pancreatitis, panniculitis, Pick's disease, polyarteritis nodosa (PAN), progressive subcortical gliosis, proteinuria, reduced glomerular filtration rate (GFR), or renovascular disorder; multiple organ failure, multiple system atrophy (MSA), myotonic dystrophy, Niemann-Pick disease type C, chronic demyelinating diseases, or progressive supranuclear palsy; spinal cord injury, spinal muscular atrophy, spondyloarthropathies, Reiter's syndrome, spontaneous fetal loss, recurrent fetal loss, pre-eclampsia, synucleinopathy, Takayasu's arteritis, post-partum thyroiditis, thyroiditis, Type I cryoglobulinemia, Type II mixed cryoglobulinemia, Type III mixed cryoglobulinemia, ulcerative colitis, uremia, urticaria, venous gas embolus (VGE), or Wegener's granulomatosis; von Hippel-Lindau disease, histoplasmosis of the eye, hard drusen, soft drusen, pigment clumping, and photoreceptor and / or retinal pigmented epithelia (RPE) loss. ALXN-0780-PCT01-NP In some embodiments, an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein is useful for treating a disorder selected from autoimmune oophoritis, endometriosis, autoimmune orchitis, Ord’s thyroiditis, autoimmune enteropathy, coeliac disease, Hashimoto’s encephalopathy, antiphospholipid syndrome (APLS) (Hughes syndrome), aplastic anemia, autoimmune lymphoproliferative syndrome (Canale-Smith syndrome), autoimmune neutropenia, Evans syndrome, pernicious anemia, pure red cell aplasia, thrombocytopenia, adipose dolorosa (Dercum’s disease), adult onset Still’s disease, ankylosing spondylitis, CREST syndrome, drug-induced lupus, eosinophilic fasciitis (Shulman’s syndrome), Felty syndrome, IgG4-related disease, mixed connective tissue disease (MCTD), palindromic rheumatism (Hench-Rosenberg syndrome), Parry-Romberg syndrome, Parsonage-Turner syndrome, relapsing polychondritis (Meyenburg-Altherr-Uehlinger syndrome), retroperitonial fibrosis, rheumatic fever, Schnitzler syndrome, fibromyalgia, neuromyotonia (Isaac’s disease), paraneoplastic degeneration, autoimmune inner ear disease, Meniere’s disease, interstitial cystitis, autoimmune pancreatitis, zika virus-related disorders, chikungunya virus-related disorders, subacute bacterial endocarditis (SBE), IgA nephropathy, IgA vasculitis, polymyalgia rheumatic, rheumatoid vasculitis, alopecia areata, autoimmune progesterone dermatitis, dermatitis herpetiformis, erythema nodosum, gestational pemphigoid, hidradenitis suppurativa, lichen sclerosus, linear IgA disease (LAD), morphea, myositis, pityriasis lichenoides et varioliformis acuta, vitiligo post-myocardial infarction syndrome (Dressler’s syndrome), post-pericardiotomy syndrome, autoimmune retinopathy, Cogan syndrome, Graves opthalmopathy, ligneous conjunctivitis, Mooren’s ulcer, opsoclonus myoclonus syndrome, optic neuritis, retinocochleocerebral vasculopathy (Susac’s syndrome), sympathetic ophthalmia, Tolosa-Hunt syndrome, interstitial lung disease, antisynthetase syndrome, Addison’s disease, autoimmune polyendocrine syndrome (APS) type I, autoimmune polyendocrine syndrome (APS) type II, autoimmune polyendocrine syndrome (APS) type III, disseminated sclerosis (multiple sclerosis, pattern II), rapidly progressing glomerulonephritis (RPGN), juvenile rheumatoid arthritis, enthesitis- related arthritis, reactive arthritis (Reiter’s syndrome), autoimmune hepatitis or lupoid hepatitis, primary biliary cirrhosis (PBS), primary sclerosing cholangitis, microscopic colitis, latent lupus (undifferentiated connective tissue disease (UCTD)), acute disseminated encephalomyelitis (ADEM), acute motor axonal neuropathy, anti- (R)-N-methyl-D-aspartate receptor encephalitis, Balo concentric sclerosis (Schilders disease), Bickerstaff’s encephalitis, chronic inflammatory demyelinating polyneuropathy, idiopathic inflammatory demyelinating disease, Lambert-Eaton mysathenic syndrome, Oshtoran syndrome, pediatric autoimmune neuropsychiatric disorder associated with streptococcus (PANDAS), progressive inflammatory neuropathy, restless leg syndrome, stiff person syndrome, Sydenhem syndrome, transverse myelitis, lupus vasculitis, leukocytoclastic vasculitis, Microscopic Polyangiitis, polymyositis, and ischemic-reperfusion injury of the eye. Examples of eye disorders that may be treated according to the compositions and methods disclosed herein include amoebic keratitis, fungal keratitis, bacterial keratitis, viral keratitis, onchocercal keratitis, bacterial keratoconjunctivitis, viral keratoconjunctivitis, corneal dystrophic diseases, Fuchs' endothelial dystrophy, Sjogren's syndrome, Stevens-Johnson syndrome, autoimmune dry eye diseases, environmental dry eye diseases, corneal neovascularization diseases, post-corneal transplant rejection prophylaxis and treatment, autoimmune uveitis, infectious uveitis, posterior uveitis (including toxoplasmosis), pan-uveitis, an inflammatory disease of the vitreous or retina, endophthalmitis prophylaxis and treatment, macular edema, ALXN-0780-PCT01-NP macular degeneration, age related macular degeneration, proliferative and non-proliferative diabetic retinopathy, hypertensive retinopathy, an autoimmune disease of the retina, primary and metastatic intraocular melanoma, other intraocular metastatic tumors, open angle glaucoma, closed angle glaucoma, pigmentary glaucoma, and combinations thereof. In a further embodiment, the disorder is selected from glaucoma, diabetic retinopathy, blistering cutaneous diseases (including bullous pemphigoid, pemphigus, and epidermolysis bullosa), ocular cicatricial pemphigoid, uveitis, adult macular degeneration, diabetic retinopathy, retinitis pigmentosa, macular edema, diabetic macular edema, Behcet's uveitis, multifocal choroiditis, Vogt-Koyanagi-Harada syndrome, intermediate uveitis, birdshot retinochorioditis, sympathetic ophthalmia, ocular cicatricial pemphigoid, ocular pemphigus, nonarteritic ischemic optic neuropathy, postoperative inflammation, and retinal vein occlusion, and central retinal vein occlusion (CVRO). In some embodiments, a method for the treatment of an autoimmune blistering disease in a subject is provided that includes the administration of an effective amount of an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein. In some embodiments, a method for the treatment of bullous pemphigoid in a subject is provided that includes the administration of an effective amount of an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein. In some embodiments, the complement mediated disorder is an ophthalmic disease (e.g., early or neovascular age-related macular degeneration and geographic atrophy), an autoimmune disease (e.g., arthritis or rheumatoid arthritis), a respiratory diseases, or a cardiovascular disease. In other embodiments, the compounds of the disclosure are suitable for use in the treatment of diseases and disorders associated with fatty acid metabolism, including obesity and other metabolic disorders. In some embodiments, a method for the treatment of geographic atrophy in a subject is provided that includes the administration of an effective amount of an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein. Disorders that may be treated or prevented by an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein also include, but are not limited to: hereditary angioedema, capillary leak syndrome, hemolytic uremic syndrome (HUS), neurological disorders, Guillain-Barré Syndrome, diseases of the central nervous system and other neurodegenerative conditions, glomerulonephritis (including membrane proliferative glomerulonephritis), SLE nephritis, proliferative nephritis, liver fibrosis, tissue regeneration and neural regeneration, or Barraquer-Simons Syndrome; inflammatory effects of sepsis, systemic inflammatory response syndrome (SIRS), disorders of inappropriate or undesirable complement activation, interleukin-2 induced toxicity during IL-2 therapy, inflammatory disorders, inflammation of autoimmune diseases, systemic lupus erythematosus (SLE), lupus nephritis, arthritis, immune complex disorders and autoimmune diseases, systemic lupus, or lupus erythematosus; ischemia / reperfusion injury (I / R injury), myocardial infarction, myocarditis, post-ischemic reperfusion conditions, balloon angioplasty, atherosclerosis, post-pump syndrome in cardiopulmonary bypass or renal bypass, renal ischemia, mesenteric artery reperfusion after aortic reconstruction, antiphospholipid syndrome, autoimmune heart disease, ischemia-reperfusion injuries, obesity, or diabetes; Alzheimer’s dementia, stroke, ALXN-0780-PCT01-NP schizophrenia, traumatic brain injury, trauma, Parkinson's disease, epilepsy, transplant rejection, prevention of fetal loss, biomaterial reactions (e.g. in hemodialysis, implants), hyperacute allograft rejection, xenograft rejection, transplantation, psoriasis, burn injury, thermal injury including burns or frostbite, or crush injury; asthma, allergy, acute respiratory distress syndrome (ARDS), cystic fibrosis, adult respiratory distress syndrome, dyspnea, hemoptysis, chronic obstructive pulmonary disease (COPD), emphysema, pulmonary embolisms and infarcts, pneumonia, fibrogenic dust diseases, inert dusts and minerals (e.g., silicon, coal dust, beryllium, and asbestos), pulmonary fibrosis, organic dust diseases, chemical injury (due to irritant gases and chemicals, e.g., chlorine, phosgene, sulfur dioxide, hydrogen sulfide, nitrogen dioxide, ammonia, and hydrochloric acid), smoke injury, thermal injury (e.g., burn, freeze), bronchoconstriction, hypersensitivity pneumonitis, parasitic diseases, Goodpasture's Syndrome (anti-glomerular basement membrane nephritis), pulmonary vasculitis, Pauci-immune vasculitis, and immune complex- associated inflammation. In some embodiments, a method for the treatment of sickle cell disease in a subject is provided that includes the administration of an effective amount of an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein. In some embodiments, a method for the treatment of immune thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), or idiopathic thrombocytopenic purpura (ITP) in a subject is provided that includes the administration of an effective amount of an active compound (e.g., a compound of Formula (I), (I’), or (I”), Table 1) or its salt or composition as described herein. In some embodiments, a method for the treatment of immune thrombocytopenic purpura (ITP). In some embodiments, a method for the treatment of ANCA-vasculitis in a subject is provided that includes the administration of an effective amount of an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein. In some embodiments, a method for the treatment of IgA nephropathy in a subject is provided that includes the administration of an effective amount of an active compound (e.g., a compound of Formula (I), (I’), or (I”), Table 1) or its salt or composition as described herein. In some embodiments, a method for the treatment of rapidly progressing glomerulonephritis (RPGN), in a subject is provided that includes the administration of an effective amount of an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein. In some embodiments, a method for the treatment of lupus nephritis, in a subject is provided that includes the administration of an effective amount of an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein. In some embodiments, a method for the treatment of hemorrhagic dengue fever, in a subject is provided that includes the administration of an effective amount of an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein. In an additional alternative embodiment, an active compound (e.g., a compound of Formula (I), (I’), or (I”), Table 1) or its salt or composition as described herein is used in the treatment of an autoimmune disorder. The complement pathway enhances the ability of antibodies and phagocytic cells to clear microbes and damaged cells from the body. It is part of the innate immune system and in healthy individuals is an essential process. Inhibiting the complement pathway will decrease the body’s immune system response. ALXN-0780-PCT01-NP Therefore, it is an object of the present disclosure to treat autoimmune disorders by administering an effective does of an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein to a subject in need thereof. In some embodiments, the autoimmune disorder is caused by activity of the complement system. In some embodiments the autoimmune disorder is caused by activity of the alternative complement pathway. In some embodiments the autoimmune disorder is caused by activity of the classical complement pathway. In another embodiment the autoimmune disorder is caused by a mechanism of action that is not directly related to the complement system, such as the over-proliferation of T-lymphocytes or the over-production of cytokines. Non-limiting examples of autoimmune disorders include: lupus, allograft rejection, autoimmune thyroid diseases (such as Graves' disease and Hashimoto's thyroiditis), autoimmune uveoretinitis, giant cell arteritis, inflammatory bowel diseases (including Crohn's disease, ulcerative colitis, regional enteritis, granulomatous enteritis, distal ileitis, regional ileitis, and terminal ileitis), diabetes, multiple sclerosis, pernicious anemia, psoriasis, rheumatoid arthritis, sarcoidosis, and scleroderma. In some embodiments, an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein is used in the treatment of lupus. Non-limiting examples of lupus include lupus erythematosus, cutaneous lupus, discoid lupus erythematosus, chilblain lupus erythematosus, and lupus erythematosus-lichen planus overlap syndrome. Lupus erythematosus is a general category of disease that includes both systemic and cutaneous disorders. The systemic form of the disease can have cutaneous as well as systemic manifestations. However, there are also forms of the disease that are only cutaneous without systemic involvement. For example, SLE is an inflammatory disorder of unknown etiology that occurs predominantly in women, and is characterized by articular symptoms, butterfly erythema, recurrent pleurisy, pericarditis, generalized adenopathy, splenomegaly, as well as CNS involvement and progressive renal failure. The sera of most patients (over 98%) contain antinuclear antibodies, including anti-DNA antibodies. High titers of anti-DNA antibodies are essentially specific for SLE. Conventional treatment for this disease has been the administration of corticosteroids or immunosuppressants. There are three forms of cutaneous lupus: chronic cutaneous lupus (also known as discoid lupus erythematosus or DLE), subacute cutaneous lupus, and acute cutaneous lupus. DLE is a disfiguring chronic disorder primarily affecting the skin with sharply circumscribed macules and plaques that display erythema, follicular plugging, scales, telangiectasia, and atrophy. The condition is often precipitated by sun exposure, and the early lesions are erythematous, round scaling papules that are 5 to 10 mm in diameter and display follicular plugging. DLE lesions appear most commonly on the cheeks, nose, scalp, and ears, but they may also be generalized over the upper portion of the trunk, extensor surfaces of the extremities, and on the mucous membranes of the mouth. If left untreated, the central lesion atrophies and leaves a scar. Unlike SLE, antibodies against double-stranded DNA (e.g., DNA-binding test) are almost invariably absent in DLE. Diabetes can refer to either type 1 or type 2 diabetes. In some embodiments an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein is provided at an effective dose to treat a patient with type 1 diabetes. In some embodiments an active ALXN-0780-PCT01-NP compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein is provided at an effective dose to treat a patient with type 2 diabetes. Type 1 diabetes is an autoimmune disease. An autoimmune disease results when the body's system for fighting infection (the immune system) attacks a part of the body. In the case of diabetes type 1, the pancreas then produces little or no insulin. In some embodiments, the complement-mediated disease or disorder comprises transplant rejection. In some embodiments, the complement-mediated disease or disorder is antibody-mediated transplant rejection. In certain aspects, an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein is used to treat a proliferative disorder, including, but not limited to, cancer. Targeted cancers suitable for administration of an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt described herein include, but are not limited to, estrogen-receptor positive cancer, HER2-negative advanced breast cancer, late-line metastatic breast cancer, liposarcoma, non-small cell lung cancer, liver cancer, ovarian cancer, glioblastoma, refractory solid tumors, retinoblastoma positive breast cancer as well as retinoblastoma positive endometrial, vaginal and ovarian cancers and lung and bronchial cancers, adenocarcinoma of the colon, adenocarcinoma of the rectum, central nervous system germ cell tumors, teratomas, estrogen receptor-negative breast cancer, estrogen receptor-positive breast cancer, familial testicular germ cell tumors, HER2-negative breast cancer, HER2-positive breast cancer, male breast cancer, ovarian immature teratomas, ovarian mature teratoma, ovarian monodermal and highly specialized teratomas, progesterone receptor-negative breast cancer, progesterone receptor-positive breast cancer, recurrent breast cancer, recurrent colon cancer, recurrent extragonadal germ cell tumors, recurrent extragonadal non-seminomatous germ cell tumor, recurrent extragonadal seminomas, recurrent malignant testicular germ cell tumors, recurrent melanomas, recurrent ovarian germ cell tumors, recurrent rectal cancer, stage III extragonadal non-seminomatous germ cell tumors, stage III extragonadal seminomas, stage III malignant testicular germ cell tumors, stage III ovarian germ cell tumors, stage IV breast cancers, stage IV colon cancers, stage IV extragonadal non-seminomatous germ cell tumors, stage IV extragonadal seminoma, stage IV melanomas, stage IV ovarian germ cell tumors, stage IV rectal cancers, testicular immature teratomas, testicular mature teratomas. In particular embodiments, the targeted cancers included estrogen- receptor positive, HER2-negative advanced breast cancer, late-line metastatic breast cancer, liposarcoma, non-small cell lung cancer, liver cancer, ovarian cancer, glioblastoma, refractory solid tumors, retinoblastoma positive breast cancer as well as retinoblastoma positive endometrial, vaginal and ovarian cancers and lung and bronchial cancers, metastatic colorectal cancer, metastatic melanoma with CDK4 mutation or amplification, or cisplatin-refractory, unresectable germ cell tumors, lung cancer, bone cancer, pancreatic cancer, skin cancer, cancer of the head or neck, cutaneous or intraocular melanoma, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, colon cancer, breast cancer, uterine cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the adrenal gland, sarcoma of soft tissue, cancer of the urethra, cancer of the penis, prostate cancer, cancer of the bladder, ALXN-0780-PCT01-NP cancer of the kidney or ureter, renal cell carcinoma, carcinoma of the renal pelvis, neoplasms of the central nervous system (CNS), primary CNS lymphoma, spinal axis tumors, brain stem glioma, pituitary adenoma, fibrosarcoma, myxosarcoma, chondrosarcoma, osteosarcoma, chordoma, malignant fibrous histiocytoma, hemangiosarcoma, angiosarcoma, lymphangiosarcoma, Mesothelioma, leiomyosarcoma, rhabdomyosarcoma, squamous cell carcinoma; epidermoid carcinoma, malignant skin adnexal tumors, adenocarcinoma, hepatoma, hepatocellular carcinoma, renal cell carcinoma, hypernephroma, cholangiocarcinoma, transitional cell carcinoma, choriocarcinoma, seminoma, embryonal cell carcinoma, glioma anaplastic; glioblastoma multiforme, neuroblastoma, medulloblastoma, malignant meningioma, malignant schwannoma, neurofibrosarcoma, parathyroid carcinoma, medullary carcinoma of thyroid, bronchial carcinoid, pheochromocytoma, Islet cell carcinoma, malignant carcinoid, malignant paraganglioma, melanoma, Merkel cell neoplasm, cystosarcoma phyllodes, salivary cancers, thymic carcinomas, bladder cancer, and Wilms tumor, a blood disorder or a hematologic malignancy, including, but not limited to, myeloid disorder, lymphoid disorder, leukemia, lymphoma, myelodysplastic syndrome (MDS), myeloproliferative disease (MPD), mast cell disorder, and myeloma (e.g., multiple myeloma), among others, T-cell or NK-cell lymphoma, for example, but not limited to: peripheral T-cell lymphoma; anaplastic large cell lymphoma, for example anaplastic lymphoma kinase (ALK) positive, ALK negative anaplastic large cell lymphoma, or primary cutaneous anaplastic large cell lymphoma; angioimmunoblastic lymphoma; cutaneous T-cell lymphoma, for example mycosis fungoides, Sézary syndrome, primary cutaneous anaplastic large cell lymphoma, primary cutaneous CD30+ T-cell lymphoproliferative disorder; primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma; primary cutaneous gamma-delta T-cell lymphoma; primary cutaneous small / medium CD4+ T-cell lymphoma, and lymphomatoid papulosis; Adult T-cell Leukemia / Lymphoma (ATLL); blastic NK-cell lymphoma; enteropathy-type T-cell lymphoma; hepatosplenic gamma-delta T-cell lymphoma; lymphoblastic Lymphoma; nasal NK / T-cell lymphomas; treatment-related T- cell lymphomas; for example lymphomas that appear after solid organ or bone marrow transplantation; T-cell prolymphocytic leukemia; T-cell large granular lymphocytic leukemia; chronic lymphoproliferative disorder of NK-cells; aggressive NK cell leukemia; systemic EBV+ T-cell lymphoproliferative disease of childhood (associated with chronic active EBV infection); hydroa vacciniforme-like lymphoma; adult T-cell leukemia / lymphoma; Enteropathy-associated T-cell lymphoma; Hepatosplenic T-cell lymphoma; or Subcutaneous panniculitis-like T-cell lymphoma. In some embodiments, the methods described herein can be used to treat a subject, for example a human, with a lymphoma or lymphocytic or myelocytic proliferation disorder or abnormality. For example, the methods as described herein can be administered to a subject with a Hodgkin Lymphoma or a Non-Hodgkin Lymphoma. For example, the subject can have a Non-Hodgkin Lymphoma such as, but not limited to: an AIDS-Related Lymphoma; Anaplastic Large-Cell Lymphoma; Angioimmunoblastic Lymphoma; Blastic NK-Cell Lymphoma; Burkitt’s Lymphoma; Burkitt-like Lymphoma (Small Non-Cleaved Cell Lymphoma); Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma; Cutaneous T-Cell Lymphoma; Diffuse Large B-Cell Lymphoma; Enteropathy-Type T-Cell Lymphoma; Follicular Lymphoma; Hepatosplenic Gamma-Delta T-Cell Lymphoma; Lymphoblastic Lymphoma; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Nasal T-Cell Lymphoma; Pediatric Lymphoma; Peripheral T-Cell Lymphomas; Primary Central Nervous System ALXN-0780-PCT01-NP Lymphoma; T-Cell Leukemias; Transformed Lymphomas; Treatment-Related T-Cell Lymphomas; or Waldenstrom's Macroglobulinemia, a Hodgkin Lymphoma, such as, but not limited to: Nodular Sclerosis Classical Hodgkin’s Lymphoma (CHL); Mixed Cellularity CHL; Lymphocyte-depletion CHL; Lymphocyte-rich CHL; Lymphocyte Predominant Hodgkin Lymphoma; or Nodular Lymphocyte Predominant HL, a specific B- cell lymphoma or proliferative disorder such as, but not limited to: multiple myeloma; Diffuse large B cell lymphoma; Follicular lymphoma; Mucosa-Associated Lymphatic Tissue lymphoma (MALT); Small cell lymphocytic lymphoma; Mediastinal large B cell lymphoma; Nodal marginal zone B cell lymphoma (NMZL); Splenic marginal zone lymphoma (SMZL); Intravascular large B-cell lymphoma; Primary effusion lymphoma; or Lymphomatoid granulomatosis; B-cell prolymphocytic leukemia; Hairy cell leukemia; Splenic lymphoma / leukemia, unclassifiable; Splenic diffuse red pulp small B-cell lymphoma; Hairy cell leukemia- variant; Lymphoplasmacytic lymphoma; Heavy chain diseases, for example, Alpha heavy chain disease, Gamma heavy chain disease, Mu heavy chain disease; Plasma cell myeloma; Solitary plasmacytoma of bone; Extraosseous plasmacytoma; Primary cutaneous follicle center lymphoma; T cell / histiocyte rich large B- cell lymphoma; DLBCL associated with chronic inflammation; Epstein-Barr virus (EBV)+ DLBCL of the elderly; Primary mediastinal (thymic) large B-cell lymphoma; Primary cutaneous DLBCL, leg type; ALK+ large B-cell lymphoma; plasmablastic lymphoma; Large B-cell lymphoma arising in HHV8-associated multicentric; Castleman disease; B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma; or B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma, a leukemia, for example, an acute or chronic leukemia of a lymphocytic or myelogenous origin, such as, but not limited to: acute lymphoblastic leukemia (ALL); Acute myelogenous leukemia (AML); chronic lymphocytic leukemia (CLL); chronic myelogenous leukemia (CML); juvenile myelomonocytic leukemia (JMML); hairy cell leukemia (HCL); acute promyelocytic leukemia (a subtype of AML); large granular lymphocytic leukemia; or adult T-cell chronic leukemia. In some embodiments, the patient has an acute myelogenous leukemia, for example an undifferentiated AML (M0); myeloblastic leukemia (M1; with / without minimal cell maturation); myeloblastic leukemia (M2; with cell maturation); promyelocytic leukemia (M3 or M3 variant [M3V]); myelomonocytic leukemia (M4 or M4 variant with eosinophilia [M4E]); monocytic leukemia (M5); erythroleukemia (M6); or megakaryoblastic leukemia (M7), small cell lung cancer, retinoblastoma, HPV positive malignancies like cervical cancer and certain head and neck cancers, MYC amplified tumors such as Burkitts’ Lymphoma, and triple negative breast cancer; certain classes of sarcoma, certain classes of non-small cell lung carcinoma, certain classes of melanoma, certain classes of pancreatic cancer, certain classes of leukemia, certain classes of lymphoma, certain classes of brain cancer, certain classes of colon cancer, certain classes of prostate cancer, certain classes of ovarian cancer, certain classes of uterine cancer, certain classes of thyroid and other endocrine tissue cancers, certain classes of salivary cancers, certain classes of thymic carcinomas, certain classes of kidney cancers, certain classes of bladder cancers, and certain classes of testicular cancers. In certain aspects, an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt as described herein can be used to preserve or prevent damage to an organ or blood product. For example, an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt described herein can be used to prevent damage to an organ, tissue, cell product, or blood product, that has been ALXN-0780-PCT01-NP harvested for transplantation. In some embodiments, the organ is the heart, kidney, pancreas, lung, liver, or intestine. In some embodiments, the tissue is derived from the cornea, bone, tendon, muscle, heart valve, nerve, artery or vein, or the skin. In some embodiments, the blood product is whole blood, plasma, red blood cells or reticulocytes. In some embodiments, an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein prevents or delays the onset of at least one symptom of a complement-mediated disease or disorder in an individual. In some embodiments, an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein reduces or eliminates at least one symptom of a complement-mediated disease or disorder in an individual. Examples of symptoms include, but are not limited to, symptoms associated with autoimmune disease, cancer, hematological disease, infectious disease, inflammatory disease, ischemia-reperfusion injury, neurodegenerative disease, neurodegenerative disorder, renal disease, transplant rejection, ocular disease, vascular disease, or a vasculitis disorder. The symptom can be a neurological symptom, for example, impaired cognitive function, memory impairment, loss of motor function, etc. The symptom can also be the activity of C1s protein in a cell, tissue, or fluid of an individual. The symptom can also be the extent of complement activation in a cell, tissue, or fluid of an individual. In some embodiments, administering an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein to an individual modulates complement activation in a cell, tissue, or fluid of an individual. In some embodiments, administration of an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein to an individual inhibits complement activation in a cell, tissue, or fluid of an individual. For example, in some embodiments, an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein, when administered in one or more doses as monotherapy or in combination therapy to an individual having a complement-mediated disease or disorder, inhibits complement activation in the individual by at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, or more than 90%, compared to complement activation in the individual before treatment with the compounds described herein. In some embodiments, an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein reduces C3 deposition onto red blood cells; for example, in some embodiments, an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein reduces deposition of C3b, iC3b, etc., onto RBCs. In some embodiments, an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein inhibits complement-mediated red blood cell lysis. In some embodiments, an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein reduces C3 deposition onto platelets; for example, in some embodiments, an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein reduces deposition of C3b, iC3b, etc., onto platelets. ALXN-0780-PCT01-NP In some embodiments, administering an active compound (e.g., a compound of Formula (I), (I’), or (I”), Table 1) or its salt or composition as described herein results in an outcome selected from the group consisting of: (a) a reduction in complement activation; (b) an improvement in cognitive function; (c) a reduction in neuron loss; (d) a reduction in phospho-Tau levels in neurons; (e) a reduction in glial cell activation; (f) a reduction in lymphocyte infiltration; (g) a reduction in macrophage infiltration; (h) a reduction in antibody deposition, (i) a reduction in glial cell loss; (j) a reduction in oligodendrocyte loss; (k) a reduction in dendritic cell infiltration; (l) a reduction in neutrophil infiltration; (m) a reduction in red blood cell lysis; (n) a reduction in red blood cell phagocytosis; (o) a reduction in platelet phagocytosis; (p) a reduction in platelet lysis; (q) an improvement in transplant graft survival; (r) a reduction in macrophage mediated phagocytosis; (s) an improvement in vision; (t) an improvement in motor control; (u) an improvement in thrombus formation; (v) an improvement in clotting; (w) an improvement in kidney function; (x) a reduction in antibody mediated complement activation; (y) a reduction in autoantibody mediated complement activation; (z) an improvement in anemia; (aa) reduction of demyelination; (ab) reduction of eosinophilia; (ac) a reduction of C3 deposition on red blood cells (e.g., a reduction of deposition of C3b, iC3b, etc., onto RBCs); and (ad) a reduction in C3 deposition on platelets (e.g., a reduction of deposition of C3b, iC3b, etc., onto platelets); and (ae) a reduction of anaphylatoxin toxin production; (af) a reduction in autoantibody mediated blister formation; (ag) a reduction in autoantibody induced pruritis; (ah) a reduction in autoantibody induced erythematosus; (ai) a reduction in autoantibody mediated skin erosion; (aj) a reduction in red blood cell destruction due to transfusion reactions; (ak) a reduction in red blood cell lysis due to alloantibodies; (al) a reduction in hemolysis due to transfusion reactions; (am) a reduction in allo-antibody mediated platelet lysis; (an) a reduction in platelet lysis due to transfusion reactions; (ao) a reduction in mast cell activation; (ap) a reduction in mast cell histamine release; (aq) a reduction in vascular permeability; (ar) a reduction in edema; (as) a reduction in complement deposition on transplant graft endothelium; (at) a reduction of anaphylatoxin generation in transplant graft endothelium; (au) a reduction in the separation of the dermal-epidermal junction; (av) a reduction in the generation of anaphylatoxins in the dermal-epidermal junction; (aw) a reduction in alloantibody mediated complement activation in transplant graft endothelium; (ax) a reduction in antibody mediated loss of the neuromuscular junction; (ay) a reduction in complement activation at the neuromuscular junction; (az) a reduction in anaphylatoxin generation at the neuromuscular junction; (ba) a reduction in complement deposition at the neuromuscular junction; (bb) a reduction in paralysis; (bc) a reduction in numbness; (bd) increased bladder control; (be) increased bowel control; (bf) a reduction in mortality associated with autoantibodies; and (bg) a reduction in morbidity associated with autoantibodies. In some embodiments, an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein, when administered in one or more doses to an individual having a complement-mediated disease or disorder, is effective to achieve a reduction of at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, or more than 90%, of one or more of the following outcomes: (a) complement activation; (b) decline in cognitive function; (c) neuron loss; (d) phospho-Tau levels in neurons; (e) glial cell activation; (f) lymphocyte infiltration; (g) macrophage infiltration; (h) antibody deposition, (i) glial cell loss; (j) oligodendrocyte loss; (k) dendritic cell infiltration; (l) ALXN-0780-PCT01-NP neutrophil infiltration; (m) red blood cell lysis; (n) red blood cell phagocytosis; (o) platelet phagocytosis; (p) platelet lysis; (q) transplant graft rejection; I macrophage mediated phagocytosis; (s) vision loss; (t) antibody mediated complement activation; (u) autoantibody mediated complement activation; (v) demyelination; (w) eosinophilia; compared to the level or degree of the outcome in the individual before treatment with the active compound or its salt. In some embodiments, an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein, when administered in one or more doses to an individual having a complement-mediated disease or disorder, is effective to achieve an improvement of at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, or more than 90%, of one or more of the following outcomes: a) cognitive function; b) transplant graft survival; c) vision; d) motor control; e) thrombus formation; f) clotting; g) kidney function; and h) hematocrit (red blood cell count), compared to the level or degree of the outcome in the individual before treatment with the active compound or its salt. In some embodiments, administering an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein to an individual reduces complement activation in the individual. For example, in some embodiments, an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein, when administered in one or more doses to an individual having a complement-mediated disease or disorder, reduces complement activation in the individual by at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, or more than 90%, compared to complement activation in the individual before treatment with the active compound or its salt. In some embodiments, administering an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein improves cognitive function in the individual. For example, in some embodiments, an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) described herein, when administered in one or more doses to an individual having a complement-mediated disease or disorder, improves cognitive function in the individual by at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, or more than 90%, compared to the cognitive function in the individual before treatment with the active compound or its salt. In some embodiments, administering an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein reduces the rate of decline in cognitive function in the individual. For example, in some embodiments, an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt, when administered in one or more doses to an individual having a complement-mediated disease or disorder, reduces the rate of decline of cognitive function in the individual by at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least ALXN-0780-PCT01-NP about 90%, or more than 90%, compared to the rate of decline in cognitive function in the individual before treatment with the active compound or its salt. In some embodiments, administering an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein to an individual reduces neuron loss in the individual. For example, in some embodiments, an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt, when administered in one or more doses to an individual having a complement- mediated disease or disorder, reduces neuron loss in the individual by at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, or more than 90%, compared to neuron loss in the individual before treatment with the active compound or its salt. In some embodiments, administering an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein to an individual reduces phospho-Tau levels in the individual. For example, in some embodiments, an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt, when administered in one or more doses to an individual having a complement-mediated disease or disorder, reduces phospho-Tau in the individual by at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, or more than 90%, compared to the phospho-Tau level in the individual before treatment with the active compound or its salt. In some embodiments, administering an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein to an individual reduces glial cell activation in the individual. For example, in some embodiments, an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt, when administered in one or more doses to an individual having a complement- mediated disease or disorder, reduces glial activation in the individual by at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, or more than 90%, compared to glial cell activation in the individual before treatment with the active compound or its salt. In some embodiments, the glial cells are astrocytes or microglia. In some embodiments, administering an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein to an individual reduces lymphocyte infiltration in the individual. For example, in some embodiments, an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt, when administered in one or more doses to an individual having a complement-mediated disease or disorder, reduces lymphocyte infiltration in the individual by at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, or more than 90%, compared to lymphocyte infiltration in the individual before treatment with the active compound or its salt. In some embodiments, administering an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein to an individual reduces macrophage infiltration ALXN-0780-PCT01-NP in the individual. For example, in some embodiments, an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt, when administered in one or more doses to an individual having a complement-mediated disease or disorder, reduces macrophage infiltration in the individual by at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, or more than 90%, compared to macrophage infiltration in the individual before treatment with the active compound or its salt. In some embodiments, administering an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein to an individual reduces antibody deposition in the individual. For example, in some embodiments, an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt, when administered in one or more doses to an individual having a complement-mediated disease or disorder, reduces antibody deposition in the individual by at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, or more than 90%, compared to antibody deposition in the individual before treatment with the active compound or its salt. In some embodiments, administering an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt or composition as described herein to an individual reduces anaphylatoxin (e.g., C3a, C4a, C5a) production in an individual. For example, in some embodiments, an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt, when administered in one or more doses to an individual having a complement-mediated disease or disorder, reduces anaphylatoxin production in the individual by at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, or more than 90%, compared to the level of anaphylatoxin production in the individual before treatment with the active compound or its salt. The present disclosure provides a use of an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt of the present disclosure or a pharmaceutical composition comprising an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt of the present disclosure and a pharmaceutically acceptable excipient to treat an individual having a complement-mediated disease or disorder. In some embodiments, the present disclosure provides a use of an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt of the present disclosure to treat an individual having a complement-mediated disease or disorder. In some embodiments, the present disclosure provides a use of a pharmaceutical composition comprising an active compound (e.g., a compound of Formula (I), (I’), or (I”), or Table 1) or its salt of the present disclosure and a pharmaceutically acceptable excipient to treat an individual having a complement-mediated disease or disorder. Examples The following examples are merely illustrative and should not be construed as limiting the scope of this disclosure in any way as many variations and equivalents will become apparent to those ALXN-0780-PCT01-NP skilled in the art upon reading the present disclosure. The contents of all references, patents, and patent applications cited throughout this application are expressly incorporated herein by reference. Example 1. Non-Limiting Synthetic Examples of Compounds of the Present Disclosure The below schemes are non-limiting examples of methods to make compounds of the present disclosure. The skilled artisan will recognize that there are various modifications that can be performed to make analogs or prepare compounds in other ways. Abbreviations AcOH acetic acid B2pin2 / Pin2B2 bis(pinacolato)diboron BINAP 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl BnBr benzyl bromide (Boc2)O or Boc2O di-tert-butyl dicarbonate BrettPhos 2-(dicyclohexylphosphino)3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl BrettPhos Pd G3 [(2-dicyclohexylphosphino-3,6-dimethoxy-2′,4′,6′- triisopropyl-1,1′-biphenyl)-2- (2′-amino-1,1′ -biphenyl)]palladium(II) methanesulfonate methanesulfonate CDI carbonyl diimidazole CTAB cetrimonium bromide CuTc cuprous 2-thiophenecarboxylate DABCO 1,4-diazabicyclo[2.2.2]octane DBU 1,8-diazabicyclo[5.4.0]undec-7-ene DCM dichloromethane DDQ 2,3-dichloro-5,6-dicyano-1,4-benzoquinone DHP 3,4-dihydropyran DIBAL-H diisobutylalumium hydride DIPEA N,N-diisopropylethylamine DMBNH22,4-dimethoxybenzylamine 4-DMAP / DMAP 4-dimethylaminopyridine DMF N,N-dimethylformamide DMP Dess–Martin periodinane DMSO dimethylsulfoxide dppf 1,1'-bis(diphenylphosphino)ferrocene DPPA diphenylphosphoryl azide EDC 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide EtOAc ethyl acetate EtOH ethanol EtONa sodium ethoxide TEA triethylamine FA formic acid HATU 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium3-oxide hexafluorophosphate HBTU 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate HOBt hydroxybenzotriazole KHMDS potassium bis(trimethylsilyl)amide KOAc potassium acetate LAH lithium aluminum hydride LDA lithium diisopropylamide LiOtBu lithium tert-butoxide m-CPBA meta-chloroperoxybenzoic acid MeCN acetonitrile MeI methyl iodide MeMgBr methylmagnesium bromide ALXN-0780-PCT01-NP MeNH2 methylamine MeOH methanol Me2S dimethyl sulfide MsCl methanesulfonyl chloride MTBE methyltbutylether NaHMDS sodium bis(trimethylsilyl)amide NaOAc sodium acetate NaOMe sodium methoxide NaSEt sodium ethanethiolate NBS N-bromosuccinimide NCS N-chlorosuccinimide n-BuLi n-butyllithium NMI N-methylimidazole NMP N-methyl-2-pyrrolidone PCC pyridinium chlorochromate Pd2(dba)3 tris(dibenzylideneacetone)dipalladium(0) Pd(OAc)2 palladium acetate Pd(dppf)Cl2 [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) Pd(dtbpf)Cl2 Bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) Pd(PPh3)4 tetrakis(triphenylphosphine)palladium(0) Pd(PPh3)2Cl2 bis(triphenylphosphine)palladium(II) dichloride Pd / C palladium on carbon Pd(OH)2 / C palladium hydroxide on carbon Pd(t-Bu3P)2 bis(tri-tert-butylphosphine)palladium(0) PE petroleum ether PPh3 triphenylphosphine PPTS Pyridinium p-toluenesulfonate i-PrOH isopropyl alcohol SnCl(n-Bu)3 tributyltin chloride T3P or T3P propane phosphonic acid anhydride TBAF tetra-n-butylammonium fluoride TBD 1,5,7-triazabicyclo[4.4.0]dec-5-ene t-BuOLi lithium tert-butoxide t-BuONa sodium tert-butoxide t-BuONO tert-butyl nitrite TCFH chloro-N,N,N′,N′-tetramethylformamidinium hexafluorophosphate TFA trifluoroacetic acid THF tetrahydrofuran Ti(OEt)4titanium (IV) ethoxide TMSCH2N2trimethylsilyldiazomethane TMSCl trimethylsilyl chloride TsOH p-toluenesulfonic acid XantPhos (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphane) XPhos / X-Phos 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl XPhos Pd G2 chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino- 1,1′-biphenyl)]palladium(II) XPhos Pd G3 (2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′- biphenyl)]palladium(II) methanesulfonate GENERAL METHODS All nonaqueous reactions were performed under an atmosphere of dry argon or nitrogen gas using anhydrous solvents. The progress of reactions and the purity of target compounds were determined using one of the two liquid chromatography (LC) methods A or B disclosed herein. The structure of starting ALXN-0780-PCT01-NP materials, intermediates, and final products was confirmed by standard analytical techniques, including NMR spectroscopy and mass spectrometry. LC Method 1 Instrument: Waters Acquity Ultra Performance LC Column: ACQUITY UPLC BEH C182.1 ´ 50 mm, 1.7 mm Column Temperature: 40 °C Mobile Phase: Solvent A: H2O + 0.05% FA; Solvent B: CH3CN + 0.05% FA Flow Rate: 0.8 mL / min Gradient: 0.24 min @ 15% B, 3.5 min gradient (15-85% B), then 0.5 min @ 85% B. Detection: UV (210-410 nm) and MS (SQ in ES+ mode) Scheme 1. Synthesis of N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(4-oxo-6-phenethyl-5,6,7,8- tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetamide (Compound 2) mL) and water (2 was mg, 6.96 was at room temperature for 1 hour. The mixture was acidified with 1N aq. HCl to pH~3 and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness to give the title compound (710 mg, yield 94.7%) as a yellow solid, which was used directly in the next step without further purification. LC / MS (ESI) m / z: 217 / 219 (M+H)+. Step 2: Methyl (3-amino-6-bromopicolinoyl)glycinate To a mixture of 3-amino-6-bromopicolinic acid (710 mg, 3.29 mmol) and methyl glycinate hydrochloride (829 mg, 6.58 mmol) in DMF (10 mL) was added HATU (1.87 g, 4.94 mmol) and DIPEA (2.55 g, 19.74 mmol) at 25 °C and the mixture was stirred at room temperature overnight. The mixture was diluted with EtOAc, washed with saturated aq. NaHCO3solution and brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 50% EtOAc in PE) to give the title compound (720 mg, yield 76.4%) as a yellow solid. LC / MS (ESI) m / z: 288 / 290 (M+H)+. ALXN-0780-PCT01-NP Step 3: Methyl 2-(6-bromo-4-oxopyrido[3,2-d]pyrimidin-3(4H)-yl)acetate To a solution of methyl (3-amino-6-bromopicolinoyl)glycinate (720 mg, 2.51 mmol) in triethoxymethane (10 mL) was added TFA (1.0 mL) under N2atmosphere and the reaction mixture was stirred at 25 °C for 16 hours. The mixture was diluted with EtOAc, washed with water and brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (0 - 70% EtOAc in PE) to give the title compound (650 mg, yield 87.2%) as a yellow solid. LC / MS (ESI) m / z: 298 / 300 (M+H)+. Step 4: Methyl (E)-2-(4-oxo-6-styrylpyrido[3,2-d]pyrimidin-3(4H)-yl)acetate To a mixture of methyl 2-(6-bromo-4-oxopyrido[3,2-d]pyrimidin-3(4H)-yl)acetate (250 mg, 0.84 mmol) and (E)-styrylboronic acid (248 mg, 1.68 mmol) in DMF (5 mL) was added XPhos Pd G2(66 mg, 0.08 mmol) and Na2CO3(249 mg, 2.52 mmol) under N2atmosphere, the reaction mixture was degassed under N2atmosphere for three times and stirred at 80 °C overnight. The mixture was diluted with water and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 25% EtOAc in PE) to give the title compound (260 mg, yield 96.3%) as a yellow solid. LC / MS (ESI) m / z: 322 (M+H)+. Step 5: Methyl 2-(4-oxo-6-phenethyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetate To a solution of methyl (E)-2-(4-oxo-6-styrylpyrido[3,2-d]pyrimidin-3(4H)-yl)acetate (260 mg, 0.81 mmol) in MeOH (5 mL) was added PtO2(36 mg, 0.16 mmol) and AcOH (0.2 mL), the mixture was degassed under N2 atmosphere for three times and stirred under a H2 balloon at 50 °C overnight. The mixture was filtered, and the filtrate was concentrated to dryness to give the title compound (190 mg, yield 71.7%) as a yellow solid, which was used directly in the next step without further purification. LC / MS (ESI) m / z: 328 (M+H)+. Step 6: 2-(4-Oxo-6-phenethyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetic acid (7) To a solution of Methyl 2-(4-oxo-6-phenethyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetate (190 mg, 0.58 mmol) in MeOH (3 mL) and water (1 mL) was added LiOH^H2O (48.8 mg, 1.16 mmol) and the reaction mixture was stirred at room temperature for 1 hour. The mixture was acidified with 1N aq. HCl to pH~3 and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness to give the title compound (160 mg, yield 88.4%) as a yellow oil, which was used directly in the next step without further purification. LC / MS (ESI) m / z: 314 (M+H)+. Step 7: N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(4-oxo-6-phenethyl-5,6,7,8-tetrahydropyrido[3,2- d]pyrimidin-3(4H)-yl)acetamide (Compound 2) To a mixture of 2-(4-oxo-6-phenethyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetic acid (160 mg, 0.51 mmol) and (1H-pyrrolo[3,2-c]pyridin-2-yl)methanamine hydrochloride (140 mg, 0.77 mmol) in DMF (5 mL) was added DIPEA (396 mg, 3.06 mmol) and HATU (292 mg, 0.77 mmol) and the mixture was stirred at room temperature for 1 hour. The mixture was concentrated under reduced pressure to dryness. The residue was purified by prep-HPLC to give Compound 2 (16 mg, yield 7.1%) as a white solid.1H NMR ALXN-0780-PCT01-NP (400 MHz, CD3OD) δ 8.93 (s, 1H), 8.48 (s, 1H), 8.23 (d, J = 6.2 Hz, 1H), 7.77 (s, 2H), 7.27 - 7.22 (m, 2H), 7.21 - 7.17 (m, 2H), 7.17 - 7.12 (m, 1H), 6.87 (s, 1H), 4.74 (s, 2H), 4.67 (s, 2H), 3.24 (d, J = 6.2 Hz, 1H), 2.76 – 2.63 (m, 4H), 2.02 (m, 1H), 1.89 - 1.75 (m, 2H), 1.73 - 1.65 (m, 1H). LC / MS (ESI) m / z: 443 (M+H)+. RT (LC Method 1): 1.49 min. Scheme 2. Synthesis of (S*)-N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(4-oxo-6-phenethyl-2-phenyl- 5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetamide (Compound 3) and (R*)-N-((1H-pyrrolo[3,2- c]pyridin-2-yl)methyl)-2-(4-oxo-6-phenethyl-2-phenyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)- yl)acetamide (Compound 4) yl) 0.40 mmol) in DMF (2 mL) was added DIPEA (213 mg, 1.65 mmol) and HATU (152 mg, 0.40 mmol), and the reaction mixture was stirred at room temperature for 2 hours. The mixture was concentrated under reduced pressure to dryness to obtain a residue containing crude Compound 1. RT (LC Method 1): 1.13 min. The residue was purified by prep-HPLC and further purified by supercritical fluid chromatography (SFC) to give Compound 3 (peak 1, retention time=3.882 min) (5.1 mg, yield 3.0%) and Compound 4 (peak 2, retention time=4.587 min) (5.7 mg, yield 3.3%) as a white solid. SFC condition: Column: ChiralCel OJ, 100 x 4.6 mm I.D., 3 um, Mobile phase: A for CO2 and B for methanol (0.05% DEA), Gradient: 8 min @B 20%, Flow rate: 2.5 mL / min, Back pressure: 100 bar, Column temperature: 35 °C. Compound 3:1H NMR (400 MHz, DMSO- d6) δ 11.33 (s, 1H), 8.74 (s, 1H), 8.67 (t, J = 5.3 Hz, 1H), 8.12 (d, J = 5.5 Hz, 1H), 7.45 (d, J = 7.0 Hz, 3H), 7.41 - 7.36 (m, 2H), 7.33 (d, J = 5.5 Hz, 1H), 7.27 (t, J = 8.0 Hz, 4H), 7.18 (t, J = 6.8 Hz, 1H), 6.31 (s, 1H), 5.21 (s, 1H), 4.44 (d, J = 29.3 Hz, 4H), 3.26 (s, 1H), 2.73 - 2.59 (m, 4H), 2.01 - 1.88 (m, 2H), 1.79 - 1.66 (m, 2H). LC / MS (ESI) m / z: 519 (M+H)+. RT (LC Method 1): 1.46 min. Compound 4:1H NMR (400 MHz, DMSO- d6) δ 11.34 (s, 1H), 8.75 (s, 1H), 8.67 (s, 1H), 8.12 (d, J = 5.1 Hz, 1H), 7.45 (d, J = 6.8 Hz, 3H), 7.41 - 7.33 (m, 3H), 7.28 (q, J = 7.6 Hz, 4H), 7.18 (t, J = 6.5 Hz, 1H), 6.31 (s, 1H), 5.21 (s, 1H), 4.44 (d, J = 28.8 Hz, 4H), 3.26 (s, 1H), 2.74 - 2.58 (m, 4H), 2.02 - 1.87 (m, 2H), 1.79 - 1.65 (m, 2H). LC / MS (ESI) m / z: 519 (M+H)+. RT (LC Method 1): 1.46 min. Scheme 3. Synthesis of N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(6-(4-fluorophenyl)-4-oxo-5,6,7,8- tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)propanamide (Compound 5) ALXN-0780-PCT01-NP Step 1: Ethyl 2-(6-(4-fluorophenyl)-4-oxopyrido[3,2-d]pyrimidin-3(4H)-yl) propanoate To a mixture of ethyl 2-(6-bromo-4-oxopyrido[3,2-d]pyrimidin-3(4H)-yl)propanoate (200 mg, 0.64 mmol) and 4-fluorophenyl)boronic acid (99 mg, 0.70 mmol) in 1,4-dioxane (2 mL) and water (1 mL) was added NaHCO3 (161 mg, 1.92 mmol), Pd(PPh3)4 (75 mg, 0.06 mmol) under N2 atmosphere. The mixture was degassed under N2 atmosphere for three times and stirred under N2 atmosphere at 65 °C for 16 hours. The mixture was diluted with EtOAc, washed with water and brine, dried over anhydrous Na2SO4, filtered and concentrated to dryness. The residue was purified by flash chromatography (silica gel, 0 - 20% EtOAc in PE) to give the title compound (144 mg, yield 65.4%) as a brown solid. LC / MS (ESI) m / z: 342 (M+H)+. Step 2: 2-(6-(4-Fluorophenyl)-4-oxopyrido[3,2-d]pyrimidin-3(4H)-yl)propanoic acid To a solution of ethyl 2-(6-(4-fluorophenyl)-4-oxopyrido[3,2-d]pyrimidin-3(4H)-yl)propanoate (300 mg, 0.87 mmol) in MeOH / water (4.0 mL, v / v= 3 / 1) was added LiOH (30 mg, 0.60 mmol) and the reaction mixture was stirred at 50 °C for 2 hours. The mixture was acidified with 1N aq. HCl to pH~3 and extracted with EtOAc twice. The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give the title compound (275 mg, yield 99.2%) as a yellow solid, which was used directly in the next step without further purification. LC / MS (ESI) m / z: 314 (M+H)+. Step 3: 2-(6-(4-Fluorophenyl)-4-oxo-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)propanoic acid To a solution of 2-(6-(4-fluorophenyl)-4-oxo-5,6,7,8-tetrahydropyrido[3,2-d] pyrimidin-3(4H)- yl)propanoic acid (120 mg, 0.38 mmol) in MeOH (2 mL) was added PtO2(20 mg), the mixture was degassed under N2atmosphere for three times and stirred under a H2balloon at room temperature overnight. The mixture was filtered, and the filtrate was concentrated to dryness to give the title compound (100 mg, yield 82.4%) as a yellow solid, which was used directly in the next step without further purification. LC / MS (ESI) m / z: 318 (M+H)+. Step 4: N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(6-(4-fluorophenyl)-4-oxo-5,6,7,8-tetrahydropyrido[3,2- d]pyrimidin-3(4H)-yl)propanamide (Compound 5) To a mixture of 2-(6-(4-fluorophenyl)-4-oxo-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)- yl)propanoic acid (100 mg, 0.31 mmol) and (1H-pyrrolo[3,2-c]pyridin-2-yl)methanamine hydrochloride (86 mg, 0.47 mmol) in DMF (2 mL) was added DIPEA (122 mg, 0.94 mmol) and HATU (144 mg, 0.37 mmol) at room temperature for 1 hour. The mixture was diluted with EtOAc, washed with water and brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness. The residue was purified by prep-TLC (DCM: MeOH= 10: 1) and further purified by prep-HPLC to give Compound 5 (5.55 mg, yield 3.7%) as a white solid.1H NMR (400 MHz, CD3OD) δ 8.91 (s, 1H), 8.44 (s, 1H), 8.22 (d, J = 5.3 Hz, 1H), 7.90 (s, 1H), 7.74 (d, J = 6.0 Hz, 1H), 7.39 - 7.31 (m, 2H), 7.09 - 7.02 (m, 2H), 6.82 (s, 1H), 5.40 - 5.31 (m, 1H), 4.75 - 4.69 (m, 1H), 4.66 - 4.59 (m, 1H), 4.49 (d, J = 7.1 Hz, 1H), 2.86 - 2.76 (m, 1H), 2.62 - 2.51 (m, 1H), 2.14 (d, J = 12.5 Hz, 1H), 2.06 - 1.96 (m, 1H), 1.76 (d, J = 7.2 Hz, 3H). LC / MS (ESI) m / z: 447 (M+H)+. RT (LC Method 1): 1.46 min. The follow compounds were prepared from the appropriate aryl boronic acids / boronated via a Suzuki coupling reaction as shown in Scheme 3 (Method A). ALXN-0780-PCT01-NP # Reactant A Reactant B Reactant C Characterization Data 1H NMR (400 MHz, CD3OD) δ 8.69 (s, 1H), 8.09 (d, J = 5.6 Hz, 1H), 7.81 (s, 1H), 7.37 (s, 3H), 7.06 (t, J = 8.5 6 Hz, 2H), 6.56 (s, 1H), 4.74 (s, 2H), 4.62 (s, 2H), 4.49 (d, J = 7.7 Hz, 1H), 2.86 - 2.77 (m, 1H), 2.61 - 2.52 (m, 1H), 2.18 - 2.10 (m, 1H), 2.07 - 1.98 (m, 1H). LC / MS (ESI) (m / z): 433 (M+H)+. RT (LC Method 1): 0.88 min. 1H NMR (400 MHz, CD3OD) δ 8.88 (s, 1H), 8.22 (s, 1H), 7.67 (s, 1H), 7.52 - 7.49 (m, 2H), 7.44 (d, J = 7.6 Hz, 2H), 7.41 - 7.37 (m, 3H), 7.37 - 7.30 (m, 2H), 7.30 - 7 7.23 (m, 1H), 6.71 (s, 1H), 4.66 (s, 2H), 4.61 (s, 2H), 4.57 - 4.53 (m, 1H), 2.89 - 2.77 (m, 1H), 2.65 - 2.54 (m, 1H), 2.25 - 2.16 (m, 1H), 2.14 - 2.05 (m, 1H). LC / MS (ESI) (m / z): 491 (M+H)+. RT (LC Method 1): 1.21 min. 1H NMR (400 MHz, CD3OD) δ 8.68 (s, 1H), 8.07 (d, J = 5.3 Hz, 1H), 7.91 (s, 1H), 7.54 - 7.49 (m, 2H), 7.47 (s, 1H), 7.43 (d, J = 8.1 Hz, 2H), 7.38 (d, J = 6.0 Hz, 2H), 7.27 - 7.21 (m, 1H), 7.20 - 7.15 (m, 1H), 6.54 (s, 1H), 9 5.43 - 5.33 (m, 1H), 4.73 - 4.65 (m, 1H), 4.62 (d, J = 14.4 Hz, 2H), 2.88 - 2.75 (m, 1H), 2.65 - 2.53 (m, 1H), 2.25 - 2.16 (m, 1H), 2.11 - 2.04 (m, 1H), 1.76 (d, J = 7.2 Hz, 3H). LC / MS (ESI) m / z: 523 (M+H)+. RT (LC Method 1): 1.47 min. 1H NMR (400 MHz, CD3OD) δ 8.70 (s, 1H), 8.09 (d, J = 5.6 Hz, 1H), 7.82 (s, 1H), 7.53 (d, J = 7.9 Hz, 2H), 7.45 (t, J = 7.7 Hz, 3H), 7.40 - 7.33 (m, 2H), 7.24 (t, J = 7.41 Hz, 1H), 7.17 (t, J = 9.2 Hz, 1H), 6.57 (s, 1H), 4.76 (s, 2H), 4.63 (s, 2H), 4.57 (d, J = 7.3 Hz, 1H), 2.89 - 2.80 (m, 1H), 2.60 (m, 1H), 2.22 - 2.18 (s, 1H), 2.14 - 2.04 (m, 1H). LC / MS (ESI) m / z: 509 (M+H)+. RT (LC Method 1): 1.43 min. 1H NMR (400 MHz, DMSO-d6) δ 11.27 (s, 1H), 8.71 (s, 1H), 8.58 (t, J = 5.4 Hz, 1H), 8.10 (s, 1H), 7.54 - 7.51 (m, 1H), 7.43 - 7.40 (m, 1H), 7.37 - 7.35 (m, 1H), 7.33-5 7.30 (m, 4H), 7.27 - 7.24 (m, 1H), 7.20 - 7.17 (m, 1H), 6.21 (s, 1H), 5.65 (s, 1H), 5.00-4.74 (m, 1H), 4.54 - 4.50 (m, 1H), 4.33 (d, J = 5.2 Hz, 2H), 4.26-4.01 (m, 1H), 2.08-1.93 (m, 4H). LC / MS(ESI) m / z: 509 (M+H)+. RT (LC Method 1): 1.55 min. Compound 22 (peak 1, retention time: 9.16 mins):1H NMR (400 MHz, DMSO-d6) δ 12.15 (s, 1H), 9.07 - 8.87 (m, 2H), 8.25 (s, 1H), 7.78 (s, 1H), 7.66 (s, 1H), 7.54 - 7.48 (m, 3H), 7.45 - 7.36 (m, 2H), 7.34 - 7.25 (m, 2H), 6.71 (s, 1H), 5.54 (d, J = 1.9 Hz, 1H), 4.68 (d, J = 5.1 Hz, 2H), 4.59 - 4.49 (m, 3H), 2.33 (s, 1H), 2.08 - 1.95 (m, 4H). LC / MS (ESI) (m / z): 558 (M+H)+. [α]D20=+71 (C:2, 0.78 mol / L, MeOH). RT (LC Method 1): 1.61 min. 13aCompound 23 (peak 2, retention time: 12.99 mins). H NMR (400 MHz, DMSO-d6) δ 12.61 (s, 1H), 9.16 (s, 1H), 9.03 - 8.99 (m, 1H), 8.36 (d, J = 6.7 Hz, 1H), 7.88 (d, J = 6.3 Hz, 1H), 7.78 (s, 1H), 7.53 - 7.50 (m, 3H), 7.40 - 7.38 (m, 2H), 7.31 - 7.27 (m, 2H), 6.87 (s, 1H), 5.53 (s, 1H), 4.69 (d, J = 4.3 Hz, 2H), 4.59 (d, J = 5.7 Hz, 2H), 4.55 - 4.48 (m, 1H), 2.12 (s, 1H), 2.03 - 1.96 (m, 4H). LC / MS (ESI) (m / z): 558 (M+H)+. [α]D20=-78 (C: 0.78 mol / L, MeOH). RT (LC Method 1): 1.64 min. 1H NMR (400 MHz, CD3OD) δ 8.69 (s, 1H), 8.09 (d, J = 5.8 Hz, 1H), 7.82 (s, 1H), 7.40-7.33 (m, 2H), 7.32-7.26 (m, 1H), 7.16-7.07 (m, 2H), 6.57 (s, 1H), 4.89-4.87 (m,6 1H), 4.75 (s, 2H), 4.63 (s, 2H), 2.83-2.75 (m, 1H), 2.59- 2.49 (m, 1H), 2.22-2.16 (m, 1H), 2.11-2.04 (m, 1H). LC / MS (ESI) m / z: 433 (M+H)+. RT (LC Method 1): 0.98 min. ALXN-0780-PCT01-NP # Reactant A Reactant B Reactant C Characterization Data 1H NMR (400 MHz, CD3OD) δ 8.69 (s, 1H), 8.08 (d, J = 5.8 Hz, 1H), 7.81 (s, 1H), 7.37 - 7.32 (m, 2H), 7.16 (d, J = 7.7 Hz, 1H), 7.11 - 7.07 (m, 1H), 7.01 - 6.96 (m, 1H),9 6.56 (s, 1H), 4.74 (s, 2H), 4.62 (s, 2H), 4.54 – 4.51 (m, 1H), 2.83 - 2.76 (m, 1H), 2.57 - 2.51 (m, 1H), 2.18 - 2.12 (m, 1H), 2.07 - 2.01 (m, 1H). LC / MS (ESI) m / z: 433 (M+H)+. RT (LC Method 1): 0.97 min. 1H NMR (400 MHz, CD3OD) δ 8.70 (s, 1H), 8.09 (d, J = 5.8 Hz, 1H), 7.81 (s, 1H), 7.38 (d, J = 5.9 Hz, 1H), 7.340 (s, 4H), 6.58 (s, 1H), 4.74 (s, 2H), 4.63 (s, 2H), 4.52 – 4.46 (m, 1H), 2.86 – 2.76 (m, 1H), 2.59 – 2.50 (m, 1H), 2.19 – 2.11 (m, 1H), 2.07 – 1.98 (m, 1H). LC / MS (ESI) m / z: 449 (M+H)+. RT (LC Method 1): 1.18 min. 1H NMR (400 MHz, CD3OD) δ 8.95 (s, 1H), 8.24 (d, J = 6.4 Hz, 1H), 7.83 (s, 1H), 7.78 (d, J = 6.5 Hz, 1H), 7.44 - 7.38 (m, 2H), 7.31 - 7.24 (m, 2H), 6.89 (s, 1H), 4.781 (s, 2H), 4.70 (s, 2H), 4.67 - 4.54 (m, 1H), 2.85 -2.75 (m, 1H), 2.60 - 2.49 (m, 1H), 2.23 - 2.18 (m, 1H), 2.06 - 2.01 (m, 1H). LC / MS (ESI) m / z: 449 (M+H)+. RT (LC Method 1): 1.16 min. 1H NMR (400 MHz, CD3OD) δ 8.77 (s, 1H), 8.13 (d, J = 6.0 Hz, 1H), 7.80 (s, 1H), 7.50 (d, J = 5.6 Hz, 1H), 7.22 (d, J = 8.1 Hz, 2H), 7.15 (d, J = 8.0 Hz, 2H), 6.67 (s,6 1H), 4.65 (s, 2H), 4.58 (s, 2H), 4.48 - 4.42 (m, 1H), 2.86 - 2.74 (m, 1H), 2.61 - 2.55 (m, 1H), 2.32 (s, 3H), 2.21 - 2.11 (m, 2H). LC / MS (ESI) m / z: 429 (M+H)+. RT (LC Method 1): 1.18 min. 1H NMR (400 MHz, DMSO-d6) δ 11.37 (s, 1H), 8.85 (t, J = 5.5 Hz, 1H), 8.74 (s, 1H), 8.11 (d, J = 5.6 Hz, 1H), 7.89 (d, J = 7.7 Hz, 1H), 7.78 (s, 1H), 7.75 (d, J = 7.48 Hz, 1H), 7.35 - 7.28 (m, 3H), 7.26 - 7.24 (m, 1H), 6.45 (s, 1H), 5.92 - 5.87 (m, 1H), 4.90 - 4.85 (m, 1H), 4.70 - 4.60 (m, 2H), 4.49 (d, J = 5.6 Hz, 2H), 2.72 - 2.65 (m, 1H), 2.49 - 2.44 (m, 1H), 2.19 - 2.07 (m, 2H). LC / MS (ESI) m / z: 471 (M+H)+. RT (LC Method 1): 1.32 min. 1H NMR (400 MHz, CD3OD) δ 8.98 (d, J = 0.8 Hz, 1H), 8.32 (d, J = 5.7 Hz, 1H), 7.96 (d, J = 5.7 Hz, 1H), 7.81 (s, 1H), 7.49 (d, J = 0.7 Hz, 1H), 7.40 - 7.34 (m, 2H),3 7.09 - 7.03 (m, 2H), 4.76 - 4.72 (m, 4H), 4.52 - 4.45 (m, 1H), 2.87 - 2.77 (m, 1H), 2.61 - 2.52 (m, 1H), 2.18 - 1.98 (m, 2H). LC / MS (ESI) (m / z): 450 (M+H)+. RT (LC Method 1): 0.99 min. Compound 80:1H NMR (400 MHz, CD3OD) δ 8.75 (s, 1H), 8.11 (d, J = 6.0 Hz, 1H), 7.91 (s, 1H), 7.51 - 7.48 (m, 3H), 7.47 - 7.43 (m, 1H), 7.41 (d, J = 8.2 Hz, 2H), 7.38 - 7.32 (m, 1H), 7.27 - 7.22 (m, 1H), 7.20 - 7.14 (m, 1H), 6.62 (s, 1H), 5.39 - 5.32 (m, 1H), 4.73 - 4.68 (m, 1H), 4.60 - 4.54 (m, 2H), 2.88 - 2.80 (m, 1H), 2.62 - 2.55 (m, 1H), 2.23 - 2.17 (m, 1H), 2.14 - 2.05 (m, 1H), 1.76 (d, J = 7.3 Hz, 3H). LC / MS (ESI) (m / z): 5230, (M+H)+. RT (LC Method 1): 1.62 min. 1aCompound 81:1H NMR (400 MHz, CD3OD) δ 8.73 (d, J = 1.8 Hz, 1H), 8.11 (d, J = 6.1 Hz, 1H), 7.92 (s, 1H), 7.52 (d, J = 8.1 Hz, 2H), 7.47 - 7.41 (m, 4H), 7.38 - 7.33 (m, 1H), 7.27 - 7.22 (m, 1H), 7.20 - 7.15 (m, 1H), 6.60 (s, 1H), 5.42 - 5.36 (m, 1H), 4.70 - 4.64 (m, 1H), 4.61 - 4.55 (m, 2H), 2.87 - 2.79 (m, 1H), 2.64 - 2.56 (m, 1H), 2.24 - 2.17 (m, 1H), 2.13 - 2.05 (m, 1H), 1.76 (d, J = 7.3 Hz, 3H). LC / MS (ESI) (m / z): 523 (M+H)+. RT (LC Method 1): 1.60 min. ALXN-0780-PCT01-NP # Reactant A Reactant B Reactant C Characterization Data Compound 82:1H NMR (400 MHz, CD3OD) δ 8.77 (s, 1H), 8.13 (d, J = 6.1 Hz, 1H), 7.91 (s, 1H), 7.54 - 7.51 (m, 3H), 7.50 - 7.45 (m, 1H), 7.44 (d, J = 8.3 Hz, 2H), 7.38 - 7.33 (m, 1H), 7.24 (t, J = 7.4 Hz, 1H), 7.20 - 7.15 (m, 1H), 6.66 (s, 1H), 5.42 - 5.36 (m, 1H), 4.70 - 4.66 (m, 1H), 4.62 - 4.58 (m, 1H), 4.57 - 4.53 (m, 1H), 2.87 - 2.79 (m, 1H), 2.64 - 2.57 (m, 1H), 2.24 - 2.18 (m, 1H), 2.13 - 2.05 (m, 1H), 1.77 (d, J = 7.3 Hz, 3H). LC / MS (ESI) m / z: 523 (M+H)+. RT (LC Method 1): 1.60 min. Compound 83:1H NMR (400 MHz, CD3OD) δ 8.73 (s, 82, 1H), 8.10 (d, J = 6.0 Hz, 1H), 7.91 (s, 1H), 7.51 – 7.48 83a(m, 2H), 7.47 – 7.44 (m, 2H), 7.41 (d, J = 8.2 Hz, 2H), 7.37 – 7.32 (m, 1H), 7.25 (d, J = 7.5 Hz, 1H), 7.20 – 7.15 (m, 1H), 6.60 (s, 1H), 5.35 (d, J = 7.3 Hz, 1H), 4.70 (d, J = 15.8 Hz, 1H), 4.59 – 4.54 (m, 2H), 2.87 – 2.80 (m, 1H), 2.62 – 2.55 (m, 1H), 2.22 – 2.17 (m, 1H), 2.12 – 2.06 (m, 1H), 1.76 (d, J = 7.3 Hz, 3H).5.38 - 5.33 (m, 1H), 4.72 - 4.67 (m, 1H), 4.59 - 4.54 (m, 2H), 2.87 - 2.80 (m, 1H), 2.62 - 2.55 (m, 1H), 2.22 - 2.17 (m, 1H), 2.12 - 2.06 (m, 1H), 1.76 (d, J = 7.3 Hz, 3H). LC / MS (ESI) m / z: 523 (M+H)+. RT (LC Method 1): 1.62 min.aCompounds isolated by Chiral SFC. Compounds 22 and 23: Chiral Cel OX, 250×21.2mm I.D., 5µm, 40mL / min, 0.1% 7mol / L NH3 in MeOH); Compounds 80-83: ChiralPak IC, 250×21.2 mm I.D., 5 μm, 60 mL / min, 50% MeOH + 0.1% NH3.H2O in CO2. Scheme 4. Synthesis of N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(2-methyl-4-oxo-6-phenethyl- 5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetamide (Compound 8) triethoxyethane (4.0 mL) was added TFA (1.0 mL) under N2atmosphere, the reaction mixture was stirred at 70 °C for 2 days. The mixture was diluted with water and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 100% EtOAc in PE) to give the title compound (200 mg, yield 46.2%) as a yellow solid. LC / MS (ESI) m / z: 312 (M+H)+. Step 2: Methyl (E)-2-(2-methyl-4-oxo-6-styrylpyrido[3,2-d]pyrimidin-3(4H)-yl)acetate To a mixture of methyl 2-(6-bromo-2-methyl-4-oxopyrido[3,2-d]pyrimidin-3(4H)-yl)acetate (190 mg, 0.61 mmol) and (E)-styrylboronic acid (180 mg, 1.22 mmol) in DMF (5.0 mL) was added Na2CO3 (194 mg, 1.83 mmol) and Xphos Pd G2 (47 mg, 0.06 mmol) under N2atmosphere, the reaction mixture was degassed under N2atmosphere for three times and stirred at 100 °C overnight. The mixture was diluted with water and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness. The residue was purified by flash ALXN-0780-PCT01-NP chromatography (silica gel, 0 - 50% EtOAc in PE) to give the title compound (50 mg, yield 24.4%) as a yellow solid. LC / MS (ESI) m / z: 336 (M+H)+. Step 3: Methyl 2-(2-methyl-4-oxo-6-phenethyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetate To a mixture of methyl (E)-2-(2-methyl-4-oxo-6-styrylpyrido[3,2-d]pyrimidin-3(4H)-yl)acetate (45 mg, 0.13 mmol) in MeOH (2.0 mL) was added PtO2 (5 mg) under N2 atmosphere, the reaction mixture was degassed under N2atmosphere for three times and stirred under a H2balloon at room temperature for 2 hours. The mixture was filtered, and the filtrate was concentrated under reduced pressure to dryness to give the title compound (23 mg, yield 50.1%) as a yellow solid. LC / MS (ESI) m / z: 342 (M+H)+. Step 4: 2-(2-Methyl-4-oxo-6-phenethyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetic acid To a mixture of methyl 2-(2-methyl-4-oxo-6-phenethyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)- yl)acetate (21 mg, 0.06 mmol) in MeOH (0.5 mL) and water (0.5 mL) was added LiOH.H2O (8 mg, 0.19 mmol) under N2 atmosphere and the reaction mixture was stirred at 50 °C for 2 hours. The mixture was acidified with 1N aq. HCl to pH~3 and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated to give the title compound (17 mg, yield 84.4%) as a white solid. LC / MS (ESI) (m / z): 328 (M+H)+. Step 5: N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(2-methyl-4-oxo-6-phenethyl-5,6,7,8-tetrahydropyrido[3,2- d]pyrimidin-3(4H)-yl)acetamide (Compound 8) To a mixture of 2-(2-methyl-4-oxo-6-phenethyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)- yl)acetic acid (15 mg, 0.05 mmol) and (1H-pyrrolo[3,2-c]pyridin-2-yl)methanamine hydrochloride (19 mg, 0.1 mmol) in DMF (0.5 mL) was added DIPEA (26 mg, 0.2 mmol) and HATU (23 mg, 0.06 mmol) and the reaction mixture was stirred at room temperature for 1 hour. The mixture was diluted with EtOAc, washed with water and brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness. The residue was purified by prep-TLC (DCM: MeOH= 8: 1) and further purified by prep-HPLC to give Compound 8 (12 mg, yield 57.4%) as a white solid.1H NMR (400 MHz, CD3OD) δ 8.69 (s, 1H), 8.09 (d, J = 5.8 Hz, 1H), 7.36 (d, J = 5.7 Hz, 1H), 7.24 (q, J = 7.1 Hz, 4H), 7.16 (d, J = 6.9 Hz, 1H), 6.55 (s, 1H), 4.85 - 4.84 (m, 2H), 4.61 (s, 2H), 3.22 (d, J = 5.8 Hz, 1H), 2.75 (t, J = 7.7 Hz, 2H), 2.65 (m, 2H), 2.42 (s, 3H), 2.03 (s, 1H), 1.84 (m, 2H), 1.76 - 1.66 (m, 1H). LC / MS (ESI) m / z: 457 (M+H)+. RT (LC Method 1): 1.12 min. Scheme 5. Synthesis of N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(4-oxo-6-(2-phenyloxazol-4-yl)- 5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)propanamide (Compound 10) ALXN-0780-PCT01-NP Step 1: Ethyl 2-(4-oxo-6-(2-phenyloxazol-4-yl)pyrido[3,2-d]pyrimidin-3(4H)-yl) propanoate To a mixture of ethyl 2-(6-bromo-4-oxopyrido[3,2-d]pyrimidin-3(4H)-yl)propanoate (120 mg, 0.37 mmol) and 4-(dibutyl(pentyl)stannyl)-2-phenyloxazole (270 mg, 0.6 mmol) in DMF (3 mL) was added Pd(PPh3)4 (75 mg, 0.06 mmol) under N2 atmosphere. The mixture was degassed under N2 atmosphere for three times and stirred under N2 atmosphere at 100 °C for 16 hours. The mixture was diluted with EtOAc, washed with water and brine, dried over anhydrous Na2SO4, filtered and concentrated to dryness. The residue was purified by flash chromatography (silica gel, 0 - 60% EtOAc in PE) to give the title compound (56 mg, yield 38.8%) as a brown solid. LC / MS (ESI) m / z: 391 (M+H)+. Step 2: Ethyl 2-(4-oxo-6-(2-phenyloxazol-4-yl)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)propanoate To a solution of ethyl 2-(4-oxo-6-(2-phenyloxazol-4-yl)pyrido[3,2-d]pyrimidin-3(4H)-yl)propanoate (50 mg, 0.14 mmol) in MeOH (3 mL) was added PtO2(20 mg), the mixture was degassed under N2atmosphere for three times and stirred under a H2 balloon at room temperature overnight. The mixture was filtered, and the filtrate was concentrated to dryness to give the title compound (59 mg, yield 99.0%) as a yellow solid, which was used directly in the next step without further purification. LC / MS (ESI) m / z: 395 (M+H)+. Step 3: 2-(4-oxo-6-(2-phenyloxazol-4-yl)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)propanoic acid To a solution of ethyl 2-(4-oxo-6-(2-phenyloxazol-4-yl)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)- yl)propanoate (49 mg, 0.14 mmol) in MeOH / water (4.0 mL, v / v= 3 / 1) was added LiOH (15 mg, 0.30 mmol) and the reaction mixture was stirred at 50 °C for 2 hours. The mixture was acidified with 1N aq. HCl to pH~3 and extracted with EtOAc twice. The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to give the title compound (45 mg, yield 98.9%) as a yellow solid, which was used directly in the next step without further purification. LC / MS (ESI) m / z: 367 (M+H)+. Step 4: N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(4-oxo-6-(2-phenyloxazol-4-yl)-5,6,7,8- tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)propanamide (Compound 10) To a mixture of 2-(4-oxo-6-(2-phenyloxazol-4-yl)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)- yl)propanoic acid (45 mg, 0.12 mmol) and (1H-pyrrolo[3,2-c]pyridin-2-yl)methanamine hydrochloride (27 mg, 0.15 mmol) in DMF (3 mL) was added DIPEA (61 mg, 0.47 mmol) and HATU (45 mg, 0.12 mmol) at room temperature for 1 hour. The mixture was diluted with EtOAc, washed with water and brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness. The residue was purified by prep-TLC (DCM: MeOH= 10: 1) and further purified by prep-HPLC (C18, 20-98% MeCN in water with 0.1% NH3.H2O) to give Compound 10 (1.0 mg, yield 1.64%) as a white solid.1H NMR (400 MHz, CD3OD) δ 8.68 (s, 1H), 8.09 - 8.05 (m, 1H), 8.00 - 7.95 (m, 2H), 7.93 (s, 1H), 7.51 - 7.47 (m, 3H), 7.40 - 7.36 (m, 1H), 7.08 (d, J = 11.3 Hz, 1H), 6.52 (s, 1H), 5.41 - 5.32 (m, 1H), 4.63 - 4.57 (m, 3H), 2.84 - 2.64 (m, 2H), 2.37 - 2.27 (m, 2H), 1.75 (d, J = 7.1 Hz, 3H). LC / MS (ESI) m / z: 496 (M+H)+. RT (LC Method 1): 0.95 min. The follow compounds were prepared from the appropriate tributylstannanes via a Stille coupling reaction as shown in Scheme 5 (Method B). # Reactant A Reactant B Reactant C Characterization Data 12 LC / MS (ESI) (m / z): 485 (M+H)+. ALXN-0780-PCT01-NP # Reactant A Reactant B Reactant C Characterization Data 1H NMR (400 MHz, DMSO-d6) δ 11.32 (s, 1H), 8.74 (s, 1H), 8.71 - 8.65 (m, 1H), 8.11 (d, J = 5.6 Hz, 1H), 7.99 - 7.95 (m, 2H), 7.54 - 7.50 (m, 3H), 7.49 - 7.45 (m, 3H),9 7.42 - 7.39 (m, 2H), 7.33 (d, J = 5.6 Hz, 1H), 7.12 (s, 1H), 6.31 (s, 1H), 5.88 (d, J = 2.4 Hz, 1H), 4.81 - 4.74 (m, 1H), 4.58 - 4.47 (m, 2H), 4.44 - 4.38 (m, 2H), 2.77 - 2.69 (m, 1H), 2.64 - 2.57 (m, 1H), 2.29 - 2.16 (m, 2H). LC / MS (ESI) (m / z): 558 (M+H)+. 1H NMR (400 MHz, CH3OD) δ 8.69 (s, 1H), 8.08 (d, J = 5.8 Hz, 1H), 8.01 - 7.97 (m, 2H), 7.95 (s, 1H), 7.52 -7.48 (m, 3H), 7.39 (d, J = 5.4 Hz, 1H), 7.10 (d, J = 11.1 Hz,6 1H), 6.54 (s, 1H), 5.43 - 5.34 (m, 1H), 4.84 - 4.80 (m, 1H), 4.67 - 4.56 (m, 2H), 2.87 - 2.79 (m, 1H), 2.77 - 2.67 (m, 1H), 2.40 - 2.26 (m, 2H), 1.76 (d, J = 7.3 Hz, 3H). LC / MS (ESI) m / z: 496 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ 11.36 (s, 1H), 8.85 (s, 1H), 8.73 (s, 1H), 8.10 (d, J = 5.6 Hz, 1H), 7.98 - 7.96 (m, 3H), 7.87 (s, 1H), 7.54 - 7.52 (m, 3H), 7.33 (d, J =7 5.6 Hz, 1H), 6.40 (s, 1H), 5.52 - 5.47 (m, 1H), 5.42 - 5.37 (m, 1H), 4.48 - 4.46 (m, 2H), 2.75 - 2.65 (m, 2H), 2.14 - 2.09 (m, 2H), 1.63 (d, J = 7.3 Hz, 3H). LC / MS (ESI) m / z: 496 (M+H)+. 1H NMR (400 MHz, CD3OD) δ 9.53 (s, 1H), 7.99 - 7.97 (m, 2H), 7.78 (s, 1H), 7.73 (d, 1H), 7.56 - 7.53 (m, 1H),3 7.50 - 7.48 (m, 4H), 7.10 (s, 1H), 4.80 - 4.79 (m, 1H), 4.64 (s, 2H), 4.27 (s, 2H), 2.83 - 2.79 (m, 1H), 2.72 - 2.67 (m, 1H), 2.34 - 2.28 (m, 2H). LC / MS (ESI) m / z: 544 (M+H)+. 1H NMR (400 MHz, CD3OD) δ 8.95 (s, 1H), 8.30 (d, J = 5.6 Hz, 1H), 8.00 - 7.95 (m, 2H), 7.91 (d, J = 5.6 Hz,1 1H), 7.83 (s, 1H), 7.51 - 7.46 (m, 4H), 7.10 (s, 1H), 4.83 - 4.77 (m, 2H), 4.74 - 4.73 (m, 3H), 2.86 - 2.77 (m, 1H), 2.75 - 2.65 (m, 1H), 2.40 - 2.24 (m, 2H). LC / MS (ESI) (m / z): 499 (M+H)+. 1H NMR (400 MHz, CD3OD) δ 8.68 (s, 1H), 8.07 (d, J = 5.9 Hz, 1H), 7.98 - 7.95 (m, 2H), 7.93 (s, 1H), 7.50 -3 7.47 (m, 3H), 7.39 - 7.36 (m, 1H), 7.10 - 7.06 (m, 1H), 6.53 (s, 1H), 5.41 - 5.32 (m, 1H), 4.83 - 4.80 (m, 2H), 4.60 (m, 1H), 2.81 - 2.68 (m, 2H), 2.36 - 2.27 (m, 2H), 1.74 (d, J = 7.3 Hz, 3H). LC / MS (ESI) m / z: 496 (M+H)+. 1H NMR (400 MHz, CD3OD) δ 8.66 (s, 1H), 8.08 (d, J = 4.9 Hz, 1H), 8.00 - 7.96 (m, 2H), 7.83 (s, 1H), 7.67 (s,3 1H), 7.51 - 7.47 (m, 3H), 7.35 (d, J = 4.9 Hz, 1H), 7.10 (s, 1H), 6.88 (s, 1H), 4.82 - 4.79 (m, 1H), 4.71 (s, 2H), 4.55 (s, 2H), 2.87 - 2.78 (m, 1H), 2.74 - 2.65 (m, 1H), 2.38 - 2.27 (m, 2H). LC / MS (ESI) m / z: 482 (M+H)+. 1H NMR (400 MHz, CD3OD) δ 8.67 (d, J = 9.4 Hz, 1H), 8.14 (d, J = 1.8 Hz, 1H), 8.08 (t, J = 6.1 Hz, 1H), 7.98 - 7.95 (m, 2H), 7.50 - 7.47 (m, 3H), 7.37 - 7.33 (m, 1H),6 7.08 (d, J = 1.5 Hz, 1H), 6.49 (d, J = 6.5 Hz, 1H), 5.21 - 5.16 (m, 1H), 4.80 - 4.77 (m, 1H), 4.57 (d, J = 5.6 Hz, 2H), 2.84 - 2.78 (m, 1H), 2.73 - 2.66 (m, 1H), 2.53 - 2.46 (m, 1H), 2.35 - 2.28 (m, 2H), 1.09 (d, J = 6.5 Hz, 3H), 0.85 (d, J = 3.5 Hz, 1H). LC / MS (ESI) m / z: 524 (M+H)+. 1H NMR (400 MHz, CD3OD) δ 8.75 (d, J = 0.8 Hz, 1H), 8.12 (d, J = 5.9 Hz, 1H), 7.95 – 7.90 (m, 2H), 7.85 (s, 1H), 7.53 – 7.45 (m, 2H), 7.43 – 7.38 (m, 1H), 6.64 (d, J8 = 0.7 Hz, 1H), 5.04 (t, J = 4.6 Hz, 1H), 4.77 (d, J = 1.6 Hz, 2H), 4.66 (s, 2H), 2.83 – 2.73 (m, 1H), 2.62 – 2.51 (m, 2H), 2.34 – 2.25 (m, 1H). LC / MS (ESI) (m / z): 472 (M+H)+. 1H NMR (400 MHz, CD3OD) δ 9.03 (s, 1H), 8.53 (d, J = 3.6 Hz, 1H), 8.01 - 7.96 (m, 2H), 7.86 - 7.80 (m, 2H),6 7.51 - 7.45 (m, 3H), 7.10 (s, 1H), 6.95 (s, 1H), 4.81 - 4.79 (m, 1H), 4.75 (s, 2H), 4.68 (s, 2H), 2.86 -2.78 (m, 1H), 2.74 - 2.65 (m, 1H), 2.36 - 2.24 (m, 2H). LC / MS (ESI) (m / z): 483 (M+H)+. ALXN-0780-PCT01-NP # Reactant A Reactant B Reactant C Characterization Data 1H NMR (400 MHz, DMSO-d6) δ 11.38 (s, 1H), 8.86 (t, J = 5.6 Hz, 1H), 8.73 (s, 1H), 8.11 (d, J = 5.6 Hz, 1H), 7.79 (s, 1H), 7.74 - 7.69 (m, 2H), 7.39 - 7.32 (m, 3H), 99 6.45 (s, 1H), 5.98 (d, J = 2.6 Hz, 1H), 4.91 (d, J = 3.4 Hz, 1H), 4.68 - 4.61 (m, 2H), 4.48 (d, J = 5.3 Hz, 2H), 2.71 - 2.60 (m, 2H), 2.35 - 2.29 (m, 1H), 2.25 - 2.17 (m, 1H). LC / MS (ESI) m / z: 456 (M+H)+. 1H NMR (400 MHz, CD3OD) δ 8.71 (s, 1H), 8.09 (d, J = 5.9 Hz, 1H), 8.00 - 7.97 (m, 2H), 7.50 - 7.48 (m, 3H), 7.41 (d, J = 5.9 Hz, 1H), 7.11 (s, 1H), 6.59 (s, 1H), 4.83 100 - 4.80 (m, 2H), 4.74 - 4.71 (m, 1H), 4.62 (s, 2H), 2.96 - 2.92 (m, 4H), 2.80 - 2.73 (m, 1H), 2.67 - 2.60 (m, 1H), 2.33 - 2.28 (m, 2H), 1.60 - 1.54 (m, 6H). LC / MS (ESI) m / z: 565 (M+H)+. Scheme 6. Synthesis of N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(4-oxo-6-(2-phenyloxazol-4-yl)- 5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetamide (Compound 12) Step 1: To a solution of 5-bromo-2-phenyloxazole (1.2g, 5.36 mmol) in THF (15 mL) was added LDA (5.4 mL, 10.8 mmol, 2M in THF) dropwise at -78 °C under N2 atmosphere and the mixture was stirred under N2 atmosphere at -78 °C for 3 hours. The mixture was quenched with ice-water and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 10% EtOAc in PE) to give the title compound (950 mg, yield 79.2%) as a yellow solid.1H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 5.7 Hz, 2H), 7.68 (s, 1H), 7.47 (d, J = 5.0 Hz, 3H). Step 2: 2-Phenyl-4-(tributylstannyl)oxazole To a solution of 4-bromo-2-phenyloxazole (830 mg, 3.70 mmol) in THF (10 mL) was added n-BuLi (2.0 mL, 5.2 mmol, 2.6 M in THF) dropwise under N2 atmosphere at -70 °C and the mixture was stirred at this temperature for 0.5 hours. SnCl(n-Bu)3 (1.5 g, 4.63 mmol) was added to the above mixture at -78 °C and the resulting mixture was stirred at -78 °C for 2 hours. The mixture was quenched with ice-water and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness to give the title compound (1.5 g, yield 93.8%) as a yellow oil, which was used directly in the next step without further purification. Compound 12 was then synthesized in a similar manner to Method B shown in Scheme 5, starting with methyl 2-(6-bromo-4-oxopyrido[3,2-d]pyrimidin-3(4H)-yl)acetate with 2-phenyl-4-(tributyl-stannyl)oxazole as the stannane coupling partner. The title compound was obtained as a white solid (3.8 mg, yield 4.6%).1H NMR (400 MHz, CD3OD) δ 8.75 (s, 1H), 8.12 (d, J = 4.6 Hz, 1H), 8.01 - 7.95 (m, 2H), 7.84 (s, 1H), 7.54 - 7.46 (m, 4H), 7.10 (s, 1H), 6.64 (s, 1H), 4.82 (s, 1H), 4.75 (s, 2H), 4.64 (s, 2H), 2.85 - 2.80 (m, 1H), 2.73 - 2.68 (m, 1H), 2.35 - 2.30 (m, 2H). LC / MS (ESI) m / z: 482 (M+H)+. RT (LC Method 1): 0.90 min. ALXN-0780-PCT01-NP Scheme 7. Synthesis of N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(2-morpholino-4-oxo-6-phenyl- 5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetamide (Compound 13) g, mixture was degassed under N2atmosphere for three times and stirred at 30 °C for 16 hours. The reaction mixture quenched with saturated aq. NaHCO3 solution and extracted with EtOAc. The combined organic layers were washed with water and brine, dried over anhydrous Na2SO4, filtered and concentrated to dryness. The residue was purified by flash chromatography (silica gel, 0 - 50% EtOAc in PE) to give the title compound (3.5 g, yield 64.2%) as a yellow solid. LC / MS (ESI) m / z: 314 (M+H)+. Step 2: Methyl 2-(2,4-dioxo-6-phenyl-1,4-dihydropyrido[3,2-d]pyrimidin-3(2H)-yl)acetate To a mixture of methyl 2-(6-bromo-2,4-dioxo-1,4-dihydropyrido[3,2-d]pyrimidin-3(2H)-yl)acetate (500 mg, 1.59 mmol), phenylboronic acid (195 mg, 1.59 mmol) in 1,4-dioxane (5 mL) and water (1 mL) was added NaHCO3 (403 mg, 4.79 mmol), Pd(dppf)Cl2 (117 mg, 0.15 mmol) under N2 atmosphere, the reaction mixture was degassed under N2 atmosphere for three times and stirred at 80 °C overnight. The mixture was diluted with water and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 -3% MeOH in DCM) to give the title compound (240 mg, yield 48.2%) as a yellow solid. LC / MS (ESI) m / z: 312 (M+H)+. Step 3: Methyl 2-(2-chloro-4-oxo-6-phenylpyrido[3,2-d]pyrimidin-3(4H)-yl)acetate To a solution of methyl 2-(2,4-dioxo-6-phenyl-1,4-dihydropyrido[3,2-d]pyrimidin-3(2H)-yl)acetate (150 mg, 0.48 mmol) in POCl3 (10 mL) was added DIPEA (403 mg, 4.79 mmol) under N2 atmosphere and the mixture was stirred at 120 °C for 16 hours. The mixture was concentrated under reduced pressure to dryness. The residue was neutralized with saturated aq. NaHCO3solution and extracted with EtOAc twice. The combined organic layers were washed with water and brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness to give the title compound (120 mg, yield 75.6%) as a yellow solid, which was used directly in the next step without further purification. LC / MS (ESI) m / z: 330 (M+H)+. Step 4: Methyl 2-(2-morpholino-4-oxo-6-phenylpyrido[3,2-d]pyrimidin-3(4H)-yl)acetate To a solution of methyl 2-(2-chloro-4-oxo-6-phenylpyrido[3,2-d]pyrimidin-3(4H)-yl)acetate (120 mg, 0.36 mmol) in DMF (3 mL) was added DIPEA (141 mg, 1.09 mmol) and morpholine (60 mg, 0.73 mmol) under N2atmosphere and the reaction mixture was stirred at room temperature overnight. The mixture was diluted with water and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over ALXN-0780-PCT01-NP anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 20% EtOAc in PE) to give the title compound (50 mg, yield 36.2%) as a yellow solid. LC / MS (ESI) m / z: 381 (M+H)+. Step 5: 2-(2-morpholino-4-oxo-6-phenylpyrido[3,2-d]pyrimidin-3(4H)-yl)acetic acid To a solution of methyl 2-(2-morpholino-4-oxo-6-phenylpyrido[3,2-d]pyrimidin-3(4H)-yl)acetate (50 mg, 0.13 mmol) in MeOH (3 mL) and water (1 mL) was added LiOH (9 mg, 0.19 mmol) and the mixture was stirred at room temperature overnight. The mixture was acidified with 1N aq. HCl to pH~3 and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness to give the title compound (40 mg, yield 83.3%) as a white solid, which was used directly in the next step without further purification. LC / MS (ESI) m / z: 367 (M+H)+. Step 6: 2-(2-morpholino-4-oxo-6-phenyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetic acid To a solution of 2-(2-morpholino-4-oxo-6-phenylpyrido[3,2-d]pyrimidin-3(4H)-yl)acetic acid (40 mg, 0.10 mmol) in THF (2 mL) was added PtO2 (6 mg) and a drop of AcOH, the mixture was degassed under N2 atmosphere for three times and stirred under a H2balloon at 60 °C overnight. The mixture was filtered, and the filtrate was concentrated to dryness to give the title compound (35 mg, yield 87.5%) as a yellow oil, which was used directly in the next step without further purification. LC / MS (ESI) m / z: 371 (M+H)+. Step 7: N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(2-morpholino-4-oxo-6-phenyl-5,6,7,8-tetrahydropyrido[3,2- d]pyrimidin-3(4H)-yl)acetamide (Compound 13) To a mixture of 2-(2-morpholino-4-oxo-6-phenyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)- yl)acetic acid (35 mg, 0.09 mmol) and (1H-pyrrolo[3,2-c]pyridin-2-yl)methanamine hydrochloride (26 mg, 0.14 mmol) in DMF (2 mL) were added DIPEA (74 mg, 0.56 mmol) and HATU (54 mg, 0.14 mmol). The mixture was stirred at room temperature for 0.5 hour. The mixture was diluted with EtOAc, washed with water and brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 12% MeOH in DCM) and further purified by prep- HPLC to give Compound 13 (1.0 mg, yield 2.1%) as a white solid.1H NMR (400 MHz, CD3OD) δ 8.85 (s, 1H), 8.18 (s, 1H), 7.64 - 7.55 (m, 1H), 7.41 - 7.30 (m, 4H), 7.29 - 7.23 (m, 1H), 6.76 (s, 1H), 4.89 (s, 3H), 4.66 (s, 2H), 4.48 - 4.39 (m, 1H), 3.73 - 3.62 (m, 4H), 3.06 - 2.96 (m, 4H), 2.83 - 2.74 (m, 1H), 2.59 - 2.49 (m, 1H), 2.21 - 2.12 (m, 1H), 2.09 - 2.00 (m, 1H). LC / MS (ESI) (m / z): 500 (M+H)+. RT (LC Method 1): 1.05 min. Scheme 8. Synthesis of N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(6-benzyl-4-oxo-2-phenyl-5,6,7,8- tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetamide (Compound 14) ALXN-0780-PCT01-NP Step 1: Methyl 2-(6-benzyl-4-oxo-2-phenylpyrido[3,2-d]pyrimidin-3(4H)-yl)acetate To a mixture of methyl 2-(6-bromo-4-oxo-2-phenylpyrido[3,2-d]pyrimidin-3(4H)-yl)acetate (710 mg, 1.90 mmol) and potassium benzyltrifluoroborate (752 mg, 3.80 mmol) in toluene (8 mL) and water (0.8 mL) was added Pd(dppf)Cl2 (347 mg, 0.47 mmol) and TEA (960 mg, 9.49 mmol) under N2 atmosphere, the reaction mixture was degassed under N2atmosphere for three times and stirred at 100 °C overnight. The mixture was diluted with water and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 25% EtOAc in PE) to give the title compound (420 mg, yield 57.4%) as a yellow solid. LC / MS (ESI) m / z: 386 (M+H)+. Step 2: 2-(6-Benzyl-4-oxo-2-phenylpyrido[3,2-d]pyrimidin-3(4H)-yl)acetic acid To a solution of methyl 2-(6-benzyl-4-oxo-2-phenylpyrido[3,2-d]pyrimidin-3(4H)-yl)acetate (430 mg, 1.12 mmol) in THF (4 mL) / MeOH (1 mL) / water (1 mL) was added LiOH (80 mg, 3.35 mmol) and the mixture was stirred at 25°C for 2 hours. The mixture was acidified with 1N aq. HCl to pH~ 5 and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated to dryness to give the title compound (400 mg, yield 96.5%) as a yellow solid, which was used directly in the next step without further purification. LC / MS (ESI) m / z: 372 (M+H)+. Step 3: 2-(6-Benzyl-4-oxo-2-phenyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetic acid To a solution of 2-(6-benzyl-4-oxo-2-phenylpyrido[3,2-d]pyrimidin-3(4H)-yl)acetic acid (400 mg, 1.08 mmol) in THF (5 mL) was added PtO2(49 mg, 0.22 mmol) and AcOH (0.1 mL), the mixture was degassed under N2atmosphere for three times and stirred under a H2balloon at 40 °C overnight. The mixture was filtered, and the filtrate was concentrated to dryness to give the title compound (320 mg, yield 79.2%) as a yellow solid, which was used directly in the next step without further purification. LC / MS (ESI) m / z: 376 (M+H)+. Step 4: N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(6-benzyl-4-oxo-2-phenyl-5,6,7,8-tetrahydropyrido[3,2- d]pyrimidin-3(4H)-yl)acetamide (Compound 14) To a mixture of 2-(6-benzyl-4-oxo-2-phenyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetic acid (60 mg, 0.16 mmol) and (1H-pyrrolo[3,2-c]pyridin-2-yl) methanamine hydrochloride (44 mg, 0.24 mmol) in DMF (3 mL) was added DIPEA (124 mg, 0.96 mmol) and HATU (67 mg, 0.18 mmol) and the mixture was stirred at room temperature for 1 hour. The mixture was concentrated under reduced pressure to dryness. The residue was purified by prep-HPLC to give Compound 14 (5.0 mg, yield 6.2%) as a white solid.1H NMR (400 MHz, CD3OD) δ 8.70 (s, 1H), 8.12 (d, J = 5.8 Hz, 1H), 7.50 - 7.43 (m, 3H), 7.42 - 7.33 (m, 4H), 7.32 - 7.27 (m, 3H), 7.26 - 7.22 (m, 1H), 6.47 (s, 1H), 4.58 (s, 2H), 4.53 (s, 2H), 3.60 - 3.51 (m, 1H), 2.93 - 2.81 (m, 2H), 2.78 - 2.69 (m, 2H), 2.14 - 2.03 (m, 1H), 1.83 - 1.72 (m, 1H). LC / MS (ESI) m / z: 505 (M+H)+. RT (LC Method 1): 1.30 min. ALXN-0780-PCT01-NP Scheme 9. Synthesis of N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(6-(2'-fluoro-[1,1'-biphenyl]-4-yl)-2- (2-fluorophenyl)-4-oxo-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)propanamide (Compound 16) was stirred under N2atmosphere at 80 °C for 16 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to dryness to give the title compound (3 g, yield 75.0%) as a black oil, which was used directly in the next step without further purification. LC / MS (ESI) m / z: 422 (M+H)+. Step 2: Ethyl 2-(6-bromo-2-(2-fluorophenyl)-4-oxopyrido[3,2-d]pyrimidin-3(4H)-yl)propanoate To a solution of ethyl 2-(6-bromo-2-(2-fluorophenyl)-4-oxo-1,4-dihydropyrido[3,2-d]pyrimidin-3(2H)- yl)propanoate (3.0 g, 7.12 mmol) in DCM (30 mL) was added DDQ (3 g, 13.2 mmol) and the reaction mixture was stirred at room temperature overnight. The mixture was diluted with DCM, washed with saturated aq. Na2S2O3solution and brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 33% EtOAc in PE) to give the title compound (3.3 g, yield 99.9%) as a yellow oil. LC / MS (ESI) m / z: 420 (M+H)+. Compound 16 was then synthesized in a similar manner to Method A shown in Scheme 3, starting with ethyl 2-(6-bromo-2-(2-fluorophenyl)-4-oxopyrido[3,2-d]pyrimidin-3(4H)-yl)propanoate with 2-(2'-fluoro- [1,1'-biphenyl]-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane as the boronic acid coupling partner. The title compound was obtained as a white solid (20.5 mg, yield 17.6%).1H NMR (400 MHz, DMSO-d6) δ 11.10 - 10.98 (m, 1H), 8.70 (s, 1H), 8.55 - 8.35 (m, 1H), 8.08 (t, J = 5.4 Hz, 1H), 7.62 - 7.52 (m, 4H), 7.47 - 7.40 (m, 4H), 7.37 - 7.28 (m, 4H), 6.43 - 6.34 (m, 1H), 5.95 - 5.78 (m, 1H), 4.69 - 4.52 (m, 2H), 4.45 - 4.40 (m, 1H), 4.40 - 4.33 (m, 1H), 2.76 - 2.66 (m, 1H), 2.48 - 2.32 (m, 1H), 2.15 - 2.00 (m, 2H), 1.66 - 1.55 (m, 3H). LC / MS (ESI) m / z: 617 (M+H)+. RT (LC Method 1): 1.84 min. Scheme 10. Synthesis of N-(5-chloro-2-(1H-tetrazol-1-yl)benzyl)-2-(4-oxo-2,6-diphenyl-5,6,7,8- tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetamide (Compound 17) acetate (200 mg, 0.52 mmol) and phenylboronic acid (95 mg, 0.78 mmol) in 1,4-dioxane / water (5 mL, v / v= 5 / 1) was added ALXN-0780-PCT01-NP Pd(dppf)Cl2 (36.6 mg, 0.05 mmol) and NaHCO3 (196 mg, 2.34 mmol) under N2 atmosphere. The reaction mixture was degassed under N2atmosphere for three times and stirred at 100 °C overnight. The mixture was diluted with water and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 10 - 50% EtOAc in PE) to give the title compound (57 mg, yield 19.0%) as a yellow solid. LC / MS (ESI) m / z: 386 (M+H)+. Step 2: Ethyl 2-(4-oxo-2,6-diphenyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetate To a solution of ethyl 2-(4-oxo-2,6-diphenylpyrido[3,2-d]pyrimidin-3(4H)-yl)acetate (50 mg, 0.13 mmol) in AcOH (2 mL) was added PtO2(20 mg) under N2atmosphere, the reaction mixture was degassed under N2atmosphere for three times and stirred at 40 °C for 5 hours. The mixture was filtered, and the filtrate was concentrated under reduced pressure to give the title compound (45 mg, yield 88.7%) as a yellow solid, which was used directly in the next step without further purification. LC / MS (ESI) m / z: 390 (M+H)+. Step 3: 2-(4-oxo-2,6-diphenyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetic acid To a mixture of ethyl 2-(4-oxo-2,6-diphenyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetate (45 mg, 0.12 mmol) in MeOH / water (3 mL, v / v= 5 / 1) was added LiOH (21.6 mg, 0.9 mmol) and the reaction mixture was stirred at 50 °C overnight. The mixture was concentrated under reduced pressure to dryness. The residue was purified by prep-HPLC to give the title compound (30 mg, yield 46.8%) as a white solid. LC / MS (ESI) m / z: 362 (M+H)+. Step 4: N-(5-chloro-2-(1H-tetrazol-1-yl)benzyl)-2-(4-oxo-2,6-diphenyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin- 3(4H)-yl)acetamide (Compound 17) To a mixture of 2-(4-oxo-2,6-diphenyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetic acid (30 mg, 0.08 mmol) and (5-chloro-2-(1H-tetrazol-1-yl)phenyl)methanamine (18.4 mg, 0.088 mmol) in DMF (1 mL) was added HATU (36.5 ml, 0.096 mmol) and the reaction mixture was stirred at room temperature for 1 hour. The mixture was concentrated under reduced pressure to dryness. The residue was purified by prep-HPLC to give Compound 17 (10 mg, yield 22.7%) as a white solid.1H NMR (400 MHz, DMSO-d6) δ 9.83 (s, 1H), 8.67 (t, J = 5.8 Hz, 1H), 7.64 (d, J = 3.1 Hz, 2H), 7.57 (d, J = 1.3 Hz, 1H), 7.47 - 7.43 (m, 5H), 7.37 (d, J = 7.6 Hz, 1H), 7.34 (d, J = 3.8 Hz, 2H), 7.32 - 7.25 (m, 2H), 5.44 (s, 1H), 4.53 - 4.50 (m, 1H), 4.47 - 4.40 (m, 2H), 4.13 (d, J = 5.8 Hz, 2H), 3.29 (s, 1H), 2.74 - 2.67 (m, 1H), 2.44 - 2.37 (m, 1H), 2.09 - 1.99 (m, 2H). LC / MS (ESI) m / z: 553 (M+H)+. RT (LC Method 1): 2.17 min. Scheme 11. Synthesis of N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(6-(2'-fluoro-[1,1'-biphenyl]-4-yl)- 4-oxo-2-phenyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetamide (Compound 18) (3.1 g, 24.39 mmol) in EtOH (80 mL) was added iodine (7.3 g, 28.57 mmol). The reaction mixture was stirred ALXN-0780-PCT01-NP at 80 °C for 16 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to dryness to give the title compound (6.1 g, yield 64.3%) as a black oil, which was used directly in the next step without further purification. LC / MS (ESI) m / z: 390 (M+H)+. Step 2: Ethyl 2-(6-bromo-4-oxo-2-phenylpyrido[3,2-d]pyrimidin-3(4H)-yl)acetate To a solution of ethyl 2-(6-bromo-4-oxo-2-phenyl-1,4-dihydropyrido[3,2-d]pyrimidin-3(2H)-yl)acetate (6.1 g, 15.68 mmol) in DCM (60 mL) was added DDQ (7.1 g, 31.28 mmol) and the mixture was stirred at room temperature for 3 hours. The mixture was added to saturated aq. Na2S2O3 solution (20 mL), and the mixture was stirred at room temperature for 1 hour. The mixture was diluted with water and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 75% EtOAc in PE) to give the title compound (4.8 g, yield 68.0%) as a yellow solid. LC / MS (ESI) m / z: 388 (M+H)+. Compound 18 was then synthesized in a similar manner to Method A shown in Scheme 3, starting with ethyl 2-(6-bromo-4-oxo-2-phenylpyrido[3,2-d]pyrimidin-3(4H)-yl)acetate with 2-(2’-fluoro-[1,1’-biphenyl]-4- yl)-4,4,5,5-tetramethyl[1,3,2]-dioxaborolane as the boronic acid coupling partner. The title compound was obtained as a white solid (5.7 mg, yield 4.8%).1H NMR (400 MHz, DMSO-d6) δ 11.33 (s, 1H), 8.74 (s, 1H), 8.69 (t, J = 5.7 Hz, 1H), 8.11 (d, J = 5.6 Hz, 1H), 7.57 - 7.51 (m, 3H), 7.51 - 7.46 (m, 3H), 7.46 - 7.40 (m, 4H), 7.35 -7.27 (m, 3H), 6.32 (s, 1H), 5.67 (d, J = 1.9 Hz, 1H), 4.61 - 4.54 (m, 2H), 4.52 - 4.47 (m, 1H), 4.43 (d, J = 5.5 Hz, 2H), 2.77 - 2.69 (m, 1H), 2.48 - 2.39 (m, 2H), 2.14 - 2.03 (m, 2H). LC / MS (ESI) m / z: 585 (M+H)+. RT (LC Method 1): 1.70 min. Scheme 12. Synthesis of (S)-N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(2-morpholino-4-oxo-6- phenethyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetamide (Compound 20) (1.0 g, 3.19 mmol) and (E)-styrylboronic acid (946 mg, 6.37 mmol) in DMF (10 mL) was added Na2CO3 (1.01 g, 9.55 mmol) and XPhos Pd G2 (251 mg, 0.32 mmol) under N2atmosphere and the reaction mixture was stirred at 80 °C overnight. The mixture was diluted with EtOAc, washed with water and brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 60% EtOAc in PE) to give the title compound (635 mg, yield 59.1%) as a yellow solid. LC / MS (ESI) m / z: 338 (M+H)+. ALXN-0780-PCT01-NP Step 2: Methyl (E)-2-(2-chloro-4-oxo-6-styrylpyrido[3,2-d]pyrimidin-3(4H)-yl)acetate To a solution of methyl (E)-2-(2,4-dioxo-6-styryl-1,4-dihydropyrido[3,2-d]pyrimidin-3(2H)-yl)acetate (600 mg, 1.78 mmol) in POCl3 (10 mL) was added DIPEA (459 mg, 3.56 mmol) under N2 atmosphere and the reaction mixture was stirred at 130 °C for 3 days. The mixture was concentrated under reduced pressure to dryness and co-evaporated with toluene twice to give the title compound (630 mg, yield 99.7%) as a yellow solid, which was used directly in the next step without further purification. LC / MS (ESI) (m / z): 356 (M+H)+. Step 3: Methyl (E)-2-(2-morpholino-4-oxo-6-styrylpyrido[3,2-d]pyrimidin-3(4H)-yl)acetate To a mixture of methyl (E)-2-(2-chloro-4-oxo-6-styrylpyrido[3,2-d]pyrimidin-3(4H)-yl)acetate (630 mg, 1.77 mmol) and morpholine (463 mg, 5.32 mmol) in DMF (10 mL) was added DIPEA (1.37 g, 10.62 mmol) under N2 atmosphere and the reaction mixture was stirred at 25 °C overnight. The mixture was diluted with EtOAc, washed with water and brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 68% EtOAc in PE) to give the title compound (430 mg, yield 59.7%) as a yellow solid. LC / MS (ESI) m / z: 407 (M+H)+. Step 4: Methyl (S)-2-(2-morpholino-4-oxo-6-phenethyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)- yl)acetate To a solution of methyl (E)-2-(2-morpholino-4-oxo-6-styrylpyrido[3,2-d]pyrimidin-3(4H)-yl)acetate (430 mg, 1.06 mmol) in THF (10 mL) was added PtO2 (24 mg, 0.11 mmol) and AcOH (0.1 mL), the mixture was degassed under N2atmosphere for three times and stirred under a H2balloon at 50 °C for 16 hours. The mixture was filtered, and the filtrate was concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 41% EtOAc in PE) and further purified by prep-SFC (ChiralCel I.D, 250 × 30 mm, A for CO2 and 40% B for MEOH +0.1%NH3.H2O, 60 mL / min) to give the title compound (100 mg, yield 22.9%) as a yellow solid. LC / MS (ESI) m / z: 413 (M+H)+. Step 5: (S)-2-(2-morpholino-4-oxo-6-phenethyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetic acid To a solution of methyl (S)-2-(2-morpholino-4-oxo-6-phenethyl-5,6,7,8-tetrahydropyrido[3,2- d]pyrimidin-3(4H)-yl)acetate (100 mg, 0.24 mmol) in MeOH (3 mL) and water (1 mL) was added LiOH (31 mg, 0.72 mmol) and the mixture was stirred at 25 °C for 3 hours. The mixture was acidified with 1N aq. HCl to pH~3 and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness to give the title compound (90 mg, yield 93.2%) as a white solid, which was used directly in the next step without further purification. LC / MS (ESI) m / z: 399 (M+H)+. Step 7: (S)-N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(2-morpholino-4-oxo-6-phenethyl-5,6,7,8- tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetamide (Compound 20) To a mixture of (S)-2-(2-morpholino-4-oxo-6-phenethyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin- 3(4H)-yl)acetic acid (45 mg, 0.11 mmol) and (1H-pyrrolo[3,2-c]pyridin-2-yl)methanamine hydrochloride (31 mg, 0.17 mmol) in DMF (3 mL) was added DIPEA (88 mg, 0.68 mmol), HATU (52 mg, 0.14 mmol) and the mixture was stirred at room temperature for 0.5 hour. The mixture was diluted with EtOAc, washed with water and brine, the organic layer was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness. The residue was purified by prep-TLC (DCM: MeOH= 10: 1) and further purified by prep- HPLC to give Compound 20 (10 mg, yield 16.8%) as a white solid.1H NMR (400 MHz, DMSO-d6) δ 11.36 (s, ALXN-0780-PCT01-NP 1H), 8.82 - 8.74 (m, 2H), 8.14 - 8.10 (m, 1H), 7.39 - 7.33 (m, 1H), 7.30 - 7.27 (m, 1H), 7.26 - 7.22 (m, 3H), 7.19 - 7.15 (m, 1H), 6.46 (s, 1H), 4.76 (s, 1H), 4.69 (s, 2H), 4.47 (d, J = 5.3 Hz, 2H), 3.57 - 3.53 (m, 4H), 3.18 - 3.13 (m, 1H), 2.87 - 2.82 (m, 4H), 2.73 - 2.53 (m, 4H), 1.98 - 1.83 (m, 2H), 1.74 - 1.60 (m, 2H). LC / MS (ESI) (m / z): 528 (M+H)+. RT (LC Method 1): 1.35 min. Compound 21 was prepared according to the procedure above, in which the (1H-pyrrolo[3,2- c]pyridin-2-yl)methanamine hydrochloride was replaced with (5-chloro-2-(1H-tetrazol-1- yl)phenyl)methanamine (10 mg, yield 15.0%).1H NMR (400 MHz, DMSO-d6) δ 9.84 (s, 1H), 8.72 (t, J = 5.8 Hz, 1H), 7.72 (s, 1H), 7.66 - 7.62 (m, 2H), 7.30 - 7.25 (m, 2H), 7.24 - 7.21 (m, 2H), 7.19 - 7.15 (m, 1H), 4.65 (s, 1H), 4.61 (s, 2H), 4.16 (d, J = 5.7 Hz, 2H), 3.64 - 3.59 (m, 4H), 3.17 - 3.11 (m, 1H), 2.86 - 2.81 (m, 4H), 2.69 - 2.64 (m, 2H), 2.62 - 2.51 (m, 2H), 1.98 - 1.91 (m, 1H), 1.88 - 1.79 (m, 1H), 1.76 - 1.67 (m, 1H), 1.66 - 1.56 (m, 1H). LC / MS (ESI) (m / z): 590 (M+H)+. RT (LC Method 1): 2.26 min. Scheme 13. Synthesis of (S)-N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(2-(2-fluorophenyl)-4-oxo-6- phenethyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetamide (Compound 24) -yl)acetate (700 mg, , mg, - g, in DMF (15 mL) was added X-Phos Pd G2 (177 mg, 0.24 mmol) under N2atmosphere. The reaction mixture was degassed under N2 atmosphere for three times and stirred at 80 °C for 16 hours. The mixture was diluted with water and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 75% EtOAc in PE) to give the title compound (650 mg, yield 62.5%) as a yellow solid. LC / MS (ESI) m / z: 430 (M+H)+. Step 2: Ethyl (S)-2-(2-(2-fluorophenyl)-4-oxo-6-phenethyl-5,6,7,8-tetrahydropyrido [3,2-d]pyrimidin-3(4H)- yl)acetate To a solution of ethyl (E)-2-(2-(2-fluorophenyl)-4-oxo-6-styrylpyrido[3,2-d]pyrimidin-3(4H)-yl)acetate (650 mg, 1.52 mmol) in AcOH (6 mL) was added PtO2(10 mg), the mixture was degassed under N2atmosphere for three times and stirred under a H2balloon at room temperature for 6 hours. The mixture was filtered, and the filtrate was concentrated to dryness. The residue was purified by chiral SFC ((R,R)-WHELK, 250×21.2 mm I.D., 5 µm, A for CO2 and B for MeOH ( 0.1% 7 mol / L NH3 in MeOH)) to give the title compound (70 mg, yield 10.6%) as a yellow solid. LC / MS (ESI) m / z: 436 (M+H)+. ALXN-0780-PCT01-NP Step 3: (S)-2-(2-(2-fluorophenyl)-4-oxo-6-phenethyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetic acid To a solution of Ethyl (S)-2-(2-(2-fluorophenyl)-4-oxo-6-phenethyl-5,6,7,8-tetrahydropyrido[3,2- d]pyrimidin-3(4H)-yl)acetate (70 mg, 0.16 mmol) in THF / MeOH / water (5.0 mL, v / v / v = 2 / 2 / 1) was added LiOH (16 mg, 0.67 mmol) and the reaction mixture was stirred at room temperature for 2 hours. The mixture was acidified with 1N aq. HCl to pH~3 and extracted with EtOAc twice. The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give the title compound (64 mg, yield 98.0%) as a yellow oil, which was used directly in the next step without further purification. LC / MS (ESI) m / z: 408 (M+H)+. Step 4: (S)-N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(2-(2-fluorophenyl)-4-oxo-6-phenethyl-5,6,7,8- tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetamide (Compound 24) To a mixture of (S)-2-(2-(2-fluorophenyl)-4-oxo-6-phenethyl-5,6,7,8-tetrahydropyrido [3,2-d]pyrimidin- 3(4H)-yl)acetic acid (32 mg, 0.08 mmol) and (1H-pyrrolo[3,2-c]pyridin-2-yl)methanamine hydrochloride (17 mg, 0.09 mmol) in DMF (3 mL) was added DIPEA (41 mg, 0.32 mmol) and HATU (36 mg, 0.09 mmol) at 25 °C and the mixture was stirred at room temperature for 2 hours. The mixture was diluted with EtOAc, washed with water and brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 10% MeOH in DCM) and further purified by prep-HPLC to give Compound 24 (5 mg, yield 11.9%) as a white solid.1H NMR (400 MHz, DMSO-d6) δ 11.63 (s, 1H), 8.85 (s, 1H), 8.61 (t, J = 5.7 Hz, 1H), 8.18 (d, J = 5.9 Hz, 1H), 8.14 (s, 1H), 7.57 - 7.50 (m, 1H), 7.48 (d, J = 5.8 Hz, 1H), 7.40 (t, J = 6.8 Hz, 1H), 7.34 (d, J = 9.3 Hz, 1H), 7.30 - 7.25 (m, 4H), 7.20 - 7.15 (m, 2H), 6.34 (s, 1H), 5.32 (s, 1H), 4.84 (s, 1H), 4.36 (d, J = 5.5 Hz, 2H), 4.19 (s, 1H), 2.73 - 2.59 (m, 4H), 2.04 - 1.88 (m, 2H), 1.80 - 1.63 (m, 2H). [α]D20=+56. (C: 1.2 mol / L, CHCl3). LC / MS (ESI) (m / z): 537 (M+H)+. RT (LC Method 1): 1.51 min. Compound 25 was prepared according to the procedure above, in which the (1H-pyrrolo[3,2- c]pyridin-2-yl)methanamine hydrochloride was replaced with (5-chloro-2-(1H-tetrazol-1- yl)phenyl)methanamine (5 mg, yield 13.9%)1H NMR (400 MHz, DMSO-d6) δ 9.79 (s, 1H), 8.54 (t, J = 5.8 Hz, 1H), 7.61 (m, J = 3.1 Hz, 2H), 7.53 (d, J = 7.0 Hz, 1H), 7.44 (s, 1H), 7.34 - 7.23 (m, 7H), 7.22 - 7.15 (m, 2H), 5.25 (s, 1H), 4.86 - 4.48 (m, 1H), 4.36 - 4.07 (m, 1H), 4.03 (d, J = 5.8 Hz, 2H), 2.71 - 2.59 (m, 4H), 2.00 - 1.88 (m, 2H), 1.77 - 1.66 (m, 2H). [α]D20=+62 (C: 0.83 mol / L, CHCl3). LC / MS (ESI) m / z: 599 (M+H)+. RT (LC Method 1): 2.44 min.

[0002] ALXN-0780-PCT01-NP Scheme 14. Synthesis of N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(2-(2-fluorophenyl)-6-(4- morpholinophenyl)-4-oxo-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetamide (Compound 26) was was poured into ice-water mixture. Stirred for 20 minutes, the solid was collected by filtration, which was rinsed thoroughly with water and air dried to give the title compound (3.7 g, 100 % yield) as a light-yellow powder. LC / MS (ESI) m / z: 245, 247 (M+H)+. Step 2: 3-Amino-6-bromopicolinic acid To a solution of ethyl 3-amino-6-bromopicolinate (3.7 g, 15 mmol, 1 equiv.) in THF (10 mL) and MeOH (40 mL) was added a solution of NaOH (0.72 g, 18 mmol, 1.2 equiv.) in water (5 mL) at 5 °C. The reaction was allowed to warm to room temperature and stirred overnight. The reaction was concentrated and diluted with water. The mixture was acidified to pH ~4 and extracted with EtOAc. The combined organic extracts were washed with brine, dried over Na2SO4and concentrated to give the title compound (700 mg, 21 % yield) as a light-yellow solid. LC / MS (ESI) m / z: 217, 219 (M+H)+. Step 3: Methyl (3-amino-6-bromopicolinoyl)glycinate To a mixture of 3-amino-6-bromopicolinic acid (0.7 g, 3 mmol, 1 equiv.), methyl 2-aminoacetate (320 mg, 3.6 mmol, 1.2 equiv.), EDC hydrochloride (0.68 g, 3.5 mmol, 1.2 equiv), and HOBt (480 mg, 3.6 mmol, 1.2 equiv) in DMF (5 mL) was added DIPEA (1 mL, 7.08 mmol, 2 equiv.) at room temperature. After stirring for over the weekend, the reaction was diluted with water and extracted with EtOAc. The combined organic extracts were washed with brine, dried over Na2SO4and concentrated. Purification by CombiFlash chromatography (12 g column, solvent A= CH2Cl2, solvent B=MeOH, 100% A to 10% B) gave the title compound (0.6 g, 60% yield) as a brown solid. LC / MS (ESI) m / z: 288, 290 (M+H)+. Step 4: Ethyl 2-(6-bromo-2-(2-fluorophenyl)-4-oxo-1,4-dihydropyrido[3,2-d]pyrimidin-3(2H)-yl)acetate To a mixture of methyl (3-amino-6-bromopicolinoyl)glycinate (800 mg, 2.8 mmol, 1 equiv.), 2- fluorobenzaldehyde (1.2 g, 9.7 mmol, 3.5 equiv.) in EtOH (10 mL) was added I2 (0.88 g, 3.5 mmol, 1.25 equiv.) at room temperature. The reaction was heated to reflux for overnight then diluted with water, washed ALXN-0780-PCT01-NP with 15% NaHSO3 aq., and extracted with EtOAc. The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated to give the title compound (0.6 mg, 47 % yield) as a yellow oil, which was used in the next step directly. LC / MS (ESI) m / z: 408, 410 (M+H)+. Step 5: Ethyl 2-(6-bromo-2-(2-fluorophenyl)-4-oxopyrido[3,2-d]pyrimidin-3(4H)-yl)acetate A mixture of ethyl 2-(6-bromo-2-(2-fluorophenyl)-4-oxo-1,4-dihydropyrido[3,2-d]pyrimidin-3(2H)- yl)acetate (330 mg, 0.81 mmol, 1 equiv.) and DDQ (550 mg, 2.4229 mmol) in CH2Cl2 (20 mL) was stirred at room temperature for 2 hours. The reaction was diluted with CH2Cl2 and washed with 1N NaOH aq. until the organic layer turned clear. The organic extract was dried over Na2SO4, filtered and concentrated. Purification by CombiFlash chromatography (12 g column, solvent A= hexanes, solvent B=EtOAc, 100% A to 60% B) gave the title compound (330 mg, 100% yield) as a yellow oil. LC / MS (ESI) m / z: 406, 408 (M+H)+. Step 6: Ethyl 2-(2-(2-fluorophenyl)-6-(4-morpholinophenyl)-4-oxopyrido[3,2-d]pyrimidin-3(4H)-yl)acetate A mixture of ethyl 2-(6-bromo-2-(2-fluorophenyl)-4-oxopyrido[3,2-d]pyrimidin-3(4H)-yl)acetate (70 mg, 0.17 mmol, 1 equiv.), [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (8 mg, 0.0098 mmol, 0.06 equiv.), (4-morpholinophenyl)boronic acid (71 mg, 0.34 mmol, 2 equiv.), K2CO3 (70 mg, 0.51 mmol, 3 equiv) in a mixture of 1,4-dioxane (2 mL) and water (0.1 mL) was sparged with N2for 10 minutes and then heated to 90 °C for 2 hours. After cooling to room temperature, the reaction was diluted with EtOAc and water, filtered through a pad of Celite, and extracted with EtOAc. The combined organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated. Purification by CombiFlash chromatography (4 g column, solvent A= CH2Cl2, solvent B=MeOH, 100% A to 5% B) gave the title compound (90 mg, >theory yield) as a yellow wax. LC / MS (ESI) m / z: 489 (M+H)+. Step 7: Ethyl 2-(2-(2-fluorophenyl)-6-(4-morpholinophenyl)-4-oxo-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin- 3(4H)-yl)acetate A mixture of ethyl 2-(2-(2-fluorophenyl)-6-(4-morpholinophenyl)-4-oxopyrido[3,2-d]pyrimidin-3(4H)- yl)acetate (80 mg, 0.1638 mmol), 20% Palladium hydroxide on carbon (8 mg, 0.035 mmol, 0.2 equiv.), acetic acid (0.05 mL) in methanol (3 mL) was vacuum-back-filled with H2 (balloon) for 3 times. The reaction was stirred at 40 °C for overnight. The solid was filtered off over a short Celite pad, and the filtrate was concentrated and purification by CombiFlash chromatography (4 g column, solvent A= CH2Cl2, solvent B=MeOH, 100% A to 5% B) gave the title compound (70 mg, 90% yield) as a yellow wax. LC / MS (ESI) m / z: 493 (M+H)+. Step 8: 2-(2-(2-Fluorophenyl)-6-(4-morpholinophenyl)-4-oxo-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)- yl)acetic acid To a solution of ethyl 2-(2-(2-fluorophenyl)-6-(4-morpholinophenyl)-4-oxo-5,6,7,8- tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetate (70 mg, 0.14 mmol, 1 equiv.) in 4 to 1 mixture of THF and MeOH mixture (2 mL) was added 1N NaOH aq. (0.06 mL, 0.2 mmol, 1.42 equiv.) at room temperature. The reaction was stirred for 3 hours. After acidified to pH ~3, the reaction was extracted with EtOAc. The organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated to give the title compound (90 mg, >theoretical yield, which was used directly in next step. LC / MS (ESI) m / z: 465 (M+H)+. ALXN-0780-PCT01-NP Step 9: N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(2-(2-fluorophenyl)-6-(4-morpholinophenyl)-4-oxo-5,6,7,8- tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetamide (Compound 26) To a mixture of 2-(2-(2-fluorophenyl)-6-(4-morpholinophenyl)-4-oxo-5,6,7,8-tetrahydropyrido[3,2- d]pyrimidin-3(4H)-yl)acetic acid (90 mg, 0.19 mmol, 1 equiv.), 1H-pyrrolo[3,2-c]pyridin-2-ylmethanamine dihydrochloride (36 mg, 0.19 mmol, 1 equiv.), [dimethylamino(triazolo[4,5-b]pyridin-3-yloxy)methylene]- dimethyl-ammonium hexafluorophosphate (100 mg, 0.26 mmol, 0.14 equiv.) in DMF (2 mL) was added DIPEA (0.1 mL) at 0 °C. The reaction was stirred for 40 minutes and quenched with saturated NaHCO3 aq. Extracted with EtOAc, the combined organic extracts were washed with 5% LiOH aq. twice. The extract was dried over Na2SO4, filtered, and concentrated. The residue was taken into DMSO and purified on prep-HPLC to give Compound 26 (25 mg, 20% yield) as an off-white solid.1H NMR (400 MHz, DMSO-d6) δ 11.31 (s, 1H), 8.81 – 8.51 (m, 2H), 8.11 (s, 1H), 7.63 – 7.28 (m, 5H), 7.19 (d, J = 8.0 Hz, 4H), 6.93 (d, J = 8.2 Hz, 2H), 6.22 (s, 1H), 5.46 (s, 1H), 4.54 – 4.28 (m, 4H), 3.73 (t, J = 4.7 Hz, 4H), 3.08 (t, J = 4.8 Hz, 4H), 2.83 – 2.60 (m, 2H), 2.00 (m, 2H). LC / MS (ESI) m / z: 594.3 (M+H)+. RT (LC Method 1): 1.20 min. Compound 30 was prepared in accordance with the procedures set forth above starting from Step 4, using benzaldehyde in place of 2-fluorobenzaldehyde in Step 4 and [(Z)-1-ethylpent-1-enyl]boronic acid in place of (4-morpholinophenyl)boronic acid in Step 6.1H NMR (400 MHz, CD3OD) δ 8.95 (s, 1H), 8.25 (d, J = 6.4 Hz, 1H), 7.75 (d, J = 6.4 Hz, 1H), 7.56 – 7.38 (m, 5H), 6.77 (s, 1H), 4.61 (d, J = 8.2 Hz, 4H), 3.19 – 3.02 (m, 1H), 2.81 – 2.62 (m, 2H), 2.10 – 1.64 (m, 6H), 1.56 – 1.43 (m, 1H), 1.40 – 1.02 (m, 5H). LC / MS (ESI) m / z: 497 (M+H)+. RT (LC Method 1): 1.56 min. Compound 33 and Compound 34 were prepared in accordance with the procedures set forth above start from Step 6, using (2,4-difluorophenyl)boronic acid and (4-isopropylsulfonylphenyl)boronic acid, respectively, in place of (4-morpholinophenyl)boronic acid in Step 6. Compound 33:1H NMR (400 MHz, CD3OD) δ 8.76 (s, 2H), 8.14 (d, J = 6.0 Hz, 1H), 7.56 – 7.36 (m, 6H), 7.04 – 6.87 (m, 3H), 6.56 (s, 1H), 4.65 (d, J = 2.6 Hz, 4H), 3.20 (t, J = 7.1 Hz, 1H), 2.81 (dt, J = 17.8, 6.4 Hz, 2H), 2.56 (dt, J = 17.7, 6.1 Hz, 2H). LC / MS (ESI) m / z: 527 (M+H)+. RT (LC Method 1): 1.32 min. Compound 34:1H NMR (400 MHz, CD3OD) δ 8.77 (s, 1H), 8.14 (d, J = 6.0 Hz, 1H), 7.88 (d, J = 8.2 Hz, 2H), 7.67 (d, J = 8.2 Hz, 2H), 7.57 – 7.37 (m, 7H), 6.57 (s, 1H), 4.71 (dd, J = 7.4, 3.8 Hz, 1H), 4.68 – 4.50 (m, 4H), 3.35 (d, J = 6.8 Hz, 1H), 2.88 – 2.77 (m, 1H), 2.54 (dt, J = 17.8, 6.0 Hz, 1H), 2.19 (dd, J = 13.7, 6.8 Hz, 2H), 1.26 (d, J = 6.8 Hz, 6H). LC / MS (ESI) m / z: 597 (M+H)+. Scheme 15. Synthesis of (S)-N-(5-chloro-2-(1H-tetrazol-1-yl)benzyl)-2-(4-oxo-6-phenethyl-2-phenyl- 5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetamide (Compound 27) and (R)-N-(5-chloro-2-(1H- tetrazol-1-yl)benzyl)-2-(4-oxo-6-phenethyl-2-phenyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)- yl)acetamide (Compound 28) To 3(4H)- yl)acetic mg, 0.51 2- 1- (140 mg, 0.67 mmol) in DMF (2 mL) was added DIPEA (329 mg, 2.55 mmol) and HATU (255 mg, 0.67 mmol) and ALXN-0780-PCT01-NP the reaction mixture was stirred at room temperature for 2 hours. The mixture was concentrated under reduced pressure to dryness. The residue was purified by prep-HPLC and further purified by Chiral SFC (ChiralPak IB, 250×30mm I.D., 5µm, 60mL / min, CO2and MeOH + 0.1%NH3H2O) to give the title Compound 27 (5.0 mg, yield 1.7%) and Compound 28 (5.0 mg, yield 1.7%) as a white solid. Compound 27 (peak 1, retention time: 4.42 min):1H NMR (400 MHz, DMSO-d6) δ 9.83 (s, 1H), 8.64 (t, J = 5.6 Hz, 1H), 7.66 - 7.61 (m, 2H), 7.56 (s, 1H), 7.48 - 7.40 (m, 5H), 7.31 - 7.24 (m, 4H), 7.18 (t, J = 6.9 Hz, 1H), 5.12 (s, 1H), 4.48 - 4.36 (m, 2H), 4.14 - 4.08 (m, 2H), 3.28 - 3.23 (m, 1H), 2.73 - 2.58 (m, 4H), 2.01 - 1.85 (m, 2H), 1.79 - 1.65 (m, 2H). LC / MS (ESI) m / z: 581 (M+H)+. [α]D20= +60 (C: 0.050, CHCl3). RT (LC Method 1): 2.43 min. Compound 28 (peak 2, retention time: 5.31 min):1H NMR (400 MHz, DMSO-d6) δ 9.83 (s, 1H), 8.64 (t, J = 5.5 Hz, 1H), 7.68 - 7.60 (m, 2H), 7.57 (s, 1H), 7.48 - 7.39 (m, 5H), 7.32 - 7.24 (m, 4H), 7.18 (t, J = 6.7 Hz, 1H), 5.12 (s, 1H), 4.47 - 4.36 (m, 2H), 4.15 - 4.07 (m, 2H), 3.29 - 3.22 (m, 1H), 2.74 - 2.58 (m, 4H), 2.01 - 1.86 (m, 2H), 1.79 - 1.65 (m, 2H). LC / MS (ESI) m / z: 581 (M+H)+. [α]D20=-48.7 (C: 0.05, CHCl3). RT (LC Method 1): 2.43 min. Scheme 16. Synthesis of (2R)-N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(6-(4-fluorophenyl)-4-oxo- 5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)propanamide (Compound 31) Step 1: To a mixture of (tert-butoxycarbonyl)-D-alanine (10 g, 52.9 mmol) and K2CO3 (14.6 g, 105.8 mmol) in MeCN (100 mL) was added BnBr (13.6 mg, 79.4 mmol) dropwise at 0 °C under N2atmosphere, and the mixture was stirred at room temperature for 16 hours. The mixture was quenched with ice-water and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 20% EtOAc in PE) to give the title compound (14 g, yield 95.2%) as a yellow oil. LC / MS (ESI) m / z: 224 (M+H-56)+. Step 2: Benzyl D-alaninate hydrochloride A solution of benzyl (tert-butoxycarbonyl)-D-alaninate (7.0 g, 25.1 mmol) in DCM (40 mL) and HCl / 1,4-dioxane (30 mL, 4M) was stirred under N2atmosphere at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure to dryness to give the title compound (5.0 g, yield: 92.6%) as a white solid, which was used directly in the next reaction without further purification. LC / MS (ESI) m / z: 180 (M+H)+. Step 3: Benzyl (3-amino-6-bromopicolinoyl)-D-alaninate To a mixture of 3-amino-6-bromopicolinic acid (2.5 g, 11.6 mmol) and benzyl D-alaninate hydrochloride (3.0 g, 13.9 mmol) in DMF (30 mL) were added DIPEA (7.5 g, 57.8 mmol) and HATU (6.6 g, 17.4 mmol) and the reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was ALXN-0780-PCT01-NP diluted with EtOAc, washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 40% EtOAc in PE) to give the title compound (4.1 g, yield 94.0%) as a colorless oil. LC / MS (ESI) m / z: 378 (M+H)+. Step 4: Benzyl (R)-2-(6-bromo-4-oxopyrido[3,2-d]pyrimidin-3(4H)-yl)propanoate To a solution of benzyl (3-amino-6-bromopicolinoyl)-D-alaninate (4.0 g, 10.6 mmol) in triethoxymethane (35 mL) was added TFA (8 mL) and the reaction mixture was stirred at room temperature overnight. The mixture was basified with saturated aq. NaHCO3 solution to pH~8 and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to dryness The residue was purified by flash chromatography (silica gel, 0 - 60% EtOAc in PE) to give the title compound (3.5 g, yield 85.4%) as a yellow solid. LC / MS (ESI) m / z: 388 (M+H)+. Compound 31 was then synthesized in a similar manner Method A shown in Scheme 3, starting with benzyl (R)-2-(6-bromo-4-oxopyrido[3,2-d]pyrimidin-3(4H)-yl)propanoate with 4-fluorophenylboronic acid as the boronic acid coupling partner.1H NMR (400 MHz, DMSO-d6) δ 11.35 - 11.33 (m, 1H), 8.84 (t, J = 5.7 Hz, 1H), 8.73 (s, 1H), 8.13 - 8.10 (m, 1H), 7.85 (s, 1H), 7.34 - 7.29 (m, 3H), 7.17 - 7.12 (m, 2H), 6.42 (s, 1H), 5.50 - 5.46 (m, 1H), 5.42 - 5.37 (m, 1H), 4.48 - 4.44 (m, 3H), 2.69 - 2.63 (m, 1H), 2.39 - 2.32 (m, 1H), 2.00 - 1.90 (m, 2H), 1.66 - 1.62 (m, 3H). LC / MS (ESI) m / z: 447 (M+H)+. RT (LC Method 1): 1.07 min. Compound 32 was prepared based on Scheme 16. # Reactant A Reactant B Reactant C Characterization Data 1H NMR (400 MHz, DMSO-d6) δ 11.38 - 11.31 (m, 1H), 8.84 (t, J = 5.7 Hz, 1H), 8.73 (s, 1H), 8.12 - 8.10 (m, 1H), 7.85 (s, 1H), 7.35 - 7.30 (m, 3H), 7.18 - 7.12 (m, 2H), 6.42 (s, 1H), 5.50 - 32 5.46 (m, 1H), 5.43 - 5.37 (m, 1H), 4.49 - 4.44 (m, 3H), 2.69 - 2.62 (m, 1H), 2.40 - 2.32 (m, 1H), 2.02 - 1.91 (m, 2H), 1.65 - 1.62 (m, 3H). LC / MS (ESI) (m / z): 447 (M+H)+. RT (LC Method 1): 1.06 min. Scheme 17. Synthesis of N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(4-oxo-6-(2-phenyloxazol-4-yl)- 5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetamide (Compound 35) (5.2 g, 8.97 mmol) in 1,4-dioxane (30 mL) were added tricyclophosphine (502 mg, 1.79 mmol), Pd2(dba)3 (821 mg, 0.90 mmol) and LiCl (1.1 g, 26.9 mmol) under N2 atmosphere, the reaction mixture was degassed under N2atmosphere for three times and stirred at 100 °C overnight. The reaction mixture was diluted with EtOAc, washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness to give the title compound (3.5 g, yield 89.7%) as a yellow oil, which was used directly in the next step without further purification. Compound 35 was then synthesized in a similar manner to Method B shown in Scheme 5, starting with methyl 2-(6-bromo-4-oxopyrido[3,2-d]pyrimidin-3(4H)-yl)acetate with 2-phenyl-4-(tributyl-stannyl)oxazole as the stannane coupling partner.1H NMR (400 MHz, CD3OD) δ 8.72 (s, 1H), 8.10 (d, J = 5.9 Hz, 1H), 8.03 - ALXN-0780-PCT01-NP 8.00 (m, 2H), 7.82 (s, 2H), 7.51 - 7.49 (m, 3H), 7.42 (d, J = 5.9 Hz, 1H), 6.60 (s, 1H), 4.75 (s, 2H), 4.63 (s, 2H), 4.59 (t, J = 5.2 Hz, 1H), 2.85 - 2.77 (m, 1H), 2.70 - 2.62 (m, 1H), 2.30 - 2.25 (m, 2H). LC / MS (ESI) m / z: 482 (M+H)+. RT (LC Method 1): 1.04 min. Scheme 18. Synthesis of N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(4-oxo-7-phenyl-5,6,7,8- tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetamide (Compound 45) To a methyl 2- bromoacetate and the mixture was stirred under N2 atmosphere at 70 °C overnight. The mixture was quenched with saturated aq. NH4Cl solution and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 30% EtOAc in PE) to give the title compound (690 mg, yield 60.7%) as a white solid. LC / MS (ESI) m / z: 299 (M+H)+.1H NMR (400 MHz, CDCl3) δ 8.90 (d, J = 1.7 Hz, 1H), 8.26 (d, J = 2.0 Hz, 1H), 8.06 (s, 1H), 4.82 (s, 2H), 3.82 (s, 3H). Compound 45 was then synthesized in a similar manner to Method A shown in Scheme 3, starting with methyl 2-(7-bromo-4-oxopyrido[3,2-d]pyrimidin-3(4H)-yl)acetate with phenylboronic acid as the boronate coupling partner.1H NMR (400 MHz, CD3OD) δ 8.73 (s, 1H), 8.16 - 8.09 (m, 1H), 7.79 (s, 1H), 7.39 (d, J = 5.8 Hz, 1H), 7.36 - 7.31 (m, 2H), 7.28 (d, J = 7.0 Hz, 2H), 7.26 - 7.22 (m, 1H), 6.63 (d, J = 49.0 Hz, 1H), 4.73 (s, 2H), 4.63 (s, 2H), 3.52 - 3.47 (m, 1H), 3.25 (d, J = 11.6 Hz, 1H), 3.15 - 3.09 (m, 1H), 2.98 - 2.92 (m, 1H), 2.90 - 2.83 (m, 1H). LC / MS (ESI) m / z: 415 (M+H)+. RT (LC Method 1): 0.93 min. Scheme 19. Synthesis of N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(2-cyclopropyl-6-(4-fluorophenyl)- 4-oxo-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetamide (Compound 37) (4- fluorophenyl)boronic acid (366 mg, 2.61 mmol) in 1,4-dioxane (5 mL) was added aq. NaHCO3solution (2.61 mL, 5.22 mmol, 2N) and Pd(PPh3)4(195 mg, 0.21 mmol) under N2atmosphere and the reaction mixture was degassed under N2 atmosphere for three times and stirred at 80 °C for 2 hours. The mixture was diluted with EtOAc, washed with water and brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 30% EtOAc in PE) to give the title compound (400 mg, yield 79.6%) as a yellow solid. LC / MS (ESI) m / z: 304 (M+H)+. ALXN-0780-PCT01-NP Step 2: Methyl 2-(2-cyclopropyl-6-(4-fluorophenyl)-4-oxopyrido[3,2-d]pyrimidin-3(4H)-yl)acetate To a mixture of methyl (3-amino-6-(4-fluorophenyl)picolinoyl)glycinate (350 mg, 1.21 mmol) and cyclopropanecarbaldehyde (90 mg, 1.28 mmol) in EtOH (5 mL) was added I2 (352 mg, 1.38 mmol) at room temperature under N2 atmosphere, the reaction mixture was degassed under N2 atmosphere for three times and stirred at 80 °C for 16 hours. The mixture was quenched with saturated aq. Na2S2O3solution and extracted with EtOAc twice. The combined organic layers were washed with water and brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 50% EtOAc in PE) to give the title compound (40 mg, yield 9.8%) as a yellow solid. LC / MS (ESI) m / z: 354 (M+H)+. Step 3: Methyl 2-(2-cyclopropyl-6-(4-fluorophenyl)-4-oxo-5,6,7,8-tetrahydropyrido [3,2-d]pyrimidin-3(4H)- yl)acetate To a solution of methyl 2-(2-cyclopropyl-6-(4-fluorophenyl)-4-oxopyrido[3,2-d]pyrimidin-3(4H)- yl)acetate (40 mg, 0.11 mmol) in AcOH (2 mL) was added PtO2 (10 mg), the reaction mixture was degassed under N2 atmosphere for three times and stirred under a H2 balloon at room temperature for 7 hours. The mixture was filtered, and the filtrate was concentrated under reduced pressure to dryness to give the title compound (35 mg, yield 86.5%) as a yellow solid, which was used directly in the next reaction without further purification. LC / MS (ESI) m / z: 358 (M+H)+. Step 4: 2-(2-Cyclopropyl-6-(4-fluorophenyl)-4-oxo-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetic acid To a solution of methyl 2-(2-cyclopropyl-6-(4-fluorophenyl)-4-oxo-5,6,7,8-tetrahydropyrido[3,2- d]pyrimidin-3(4H)-yl)acetate (35 mg, 0.097 mmol) in MeOH / water (2.0 mL, v / v= 4 / 1) was added LiOH^H2O (8 mg, 0.19 mmol) and the reaction mixture was stirred at room temperature for 1 hour. The mixture was acidified with 1N aq. HCl to pH~3 and extracted with EtOAc twice. The combined organic layers were washed with water and brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to dryness to give the title compound (30 mg, yield 89.2%) as a yellow solid, which was used directly in the next reaction without further purification. LC / MS (ESI) m / z: 344 (M+H)+. Step 5: N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(2-cyclopropyl-6-(4-fluorophenyl)-4-oxo-5,6,7,8- tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetamide (Compound 37) To a mixture of 2-(2-cyclopropyl-6-(4-fluorophenyl)-4-oxo-5,6,7,8-tetrahydropyrido [3,2-d]pyrimidin- 3(4H)-yl)acetic acid (30 mg, 0.087 mmol) and (1H-pyrrolo[3,2-c]pyridin-2-yl)methanamine hydrochloride (24 mg, 0.13 mmol) in DMF (2 mL) was added DIPEA (56 mg, 0.43 mmol) and HATU (40 mg, 0.10 mmol) and the reaction mixture was stirred at room temperature for 1 hour. The mixture was concentrated under reduced pressure to dryness. The residue was purified by prep-HPLC to give Compound 37 (6.0 mg, yield 14.5%) as a white solid.1H NMR (400 MHz, DMSO-d6) δ 11.44 (s, 1H), 8.85 (t, J = 5.6 Hz, 1H), 8.75 (s, 1H), 8.15 (s, 1H), 8.12 (d, J = 5.7 Hz, 1H), 7.36 - 7.30 (m, 3H), 7.17 - 7.12 (m, 2H), 6.46 (s, 1H), 5.21 (d, J = 1.9 Hz, 1H), 5.00 - 4.90 (m, 2H), 4.50 (d, J = 5.5 Hz, 2H), 4.43 - 4.39 (m, 1H), 2.63 - 2.56 (m, 1H), 2.34 - 2.25 (m, 1H), 2.01 - 1.86 (m, 3H), 0.90 - 0.81 (m, 4H). LC / MS (ESI) m / z: 473 (M+H)+. RT (LC Method 1): 1.30 min. ALXN-0780-PCT01-NP Scheme 20. Synthesis of N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(6-(4-fluorophenyl)-2-methyl-4- oxo-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetamide (Compound 38) and at room temperature, the reaction mixture was degassed under N2atmosphere for three times and stirred at 80 °C for 16 hours. The mixture was concentrated under reduced pressure to dryness to give the title compound (200 mg, yield 64.4%) as a brown solid, which was used directly in the next reaction without further purification. LC / MS (ESI) m / z: 344 (M+H)+. Step 2: Ethyl 2-(6-(4-fluorophenyl)-2-methyl-4-oxopyrido[3,2-d]pyrimidin-3(4H)-yl)acetate To a solution of ethyl 2-(6-(4-fluorophenyl)-2-methyl-4-oxo-1,4-dihydropyrido[3,2-d]pyrimidin-3(2H)- yl)acetate (200 mg, 0.58 mmol) in DCM (5 mL) was added DDQ (264 mg, 1.16 mmol) at 0 °C and the reaction mixture was stirred at room temperature for 2 hours. The mixture was quenched with saturated aq. Na2S2O3solution and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 75% EtOAc in PE) and further purified by prep-TLC (DCM: MeOH= 20: 1) to give the title compound (20 mg, yield 9.6%) as a yellow solid. LC / MS (ESI) m / z: 342 (M+H)+. Step 3: Ethyl 2-(6-(4-fluorophenyl)-2-methyl-4-oxo-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetate To a solution of ethyl 2-(6-(4-fluorophenyl)-2-methyl-4-oxopyrido[3,2-d]pyrimidin-3(4H)-yl)acetate (20 mg, 0.058 mmol) in AcOH (2 mL) was added PtO2(10 mg), the reaction mixture was degassed under N2atmosphere for three times and stirred under a H2 balloon at 40 °C for 2 hours. The mixture was filtered, and the filtrate was concentrated under reduced pressure to dryness to give the title compound (18 mg, yield 88.9%) as a yellow solid, which was used directly in the next reaction without further purification. LC / MS (ESI) m / z: 346 (M+H)+. Step 4: 2-(6-(4-Fluorophenyl)-2-methyl-4-oxo-5,6,7,8-tetrahydropyrido[3,2-d] pyrimidin-3(4H)-yl)acetic acid To a solution of ethyl 2-(6-(4-fluorophenyl)-2-methyl-4-oxo-5,6,7,8-tetrahydropyrido [3,2-d]pyrimidin- 3(4H)-yl)acetate (18 mg, 0.052 mmol) in MeOH / water (2.0 mL, v / v= 4 / 1) was added LiOH^H2O (4 mg, 0.095 mmol), and the reaction mixture was stirred at room temperature for 2 hours. The mixture was acidified with 1N aq. HCl to pH~3 and extracted with EtOAc twice. The combined organic layers were washed with water and brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness to give the title compound (16 mg, yield 96.7%) as a yellow solid, which was used directly in the next step without further purification. LC / MS (ESI) m / z: 328 (M+H)+. ALXN-0780-PCT01-NP Step 5: N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(6-(4-fluorophenyl)-2-methyl-4-oxo-5,6,7,8- tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetamide (Compound 38) To a mixture of 2-(6-(4-fluorophenyl)-2-methyl-4-oxo-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)- yl)acetic acid (16 mg, 0.050 mmol) and (1H-pyrrolo[3,2-c]pyridin-2-yl)methanamine hydrochloride (14 mg, 0.076 mmol) in DMF (2 mL) was added DIPEA (32 mg, 0.24 mmol) and HATU (23 mg, 0.60 mmol) and the reaction mixture was stirred at room temeprature for 1 hour. The mixture was concentrated under reduced pressure to dryness. The residue was purified by prep-HPLC (C18, 40 - 98% MeCN in water with 0.1% NH3.H2O) to give Compound 38 (5.6 mg, yield 24.8%) as a white solid.1H NMR (400 MHz, DMSO-d6) δ 11.39 (s, 1H), 8.85 (t, J = 5.6 Hz, 1H), 8.73 (s, 1H), 8.11 (d, J = 5.7 Hz, 1H), 7.34 - 7.30 (m, 3H), 7.15 (t, J = 8.8 Hz, 2H), 6.44 (s, 1H), 5.20 (d, J = 1.9 Hz, 1H), 4.82 - 4.71 (m, 2H), 4.49 (d, J = 5.5 Hz, 2H), 4.42 (d, J = 3.4 Hz, 1H), 2.67 - 2.60 (m, 1H), 2.32 (s, 3H), 2.32 - 2.28 (m, 1H), 2.02 - 1.90 (m, 2H). LC / MS (ESI) m / z: 447 (M+H)+. RT (LC Method 1): 0.97 min. The following compounds were prepared based on Scheme 20. # Reactant A Reactant B Reactant C Characterization Data 1H NMR (400 MHz, DMSO-d6) δ 11.39 (s, 1H), 8.85 (t, J = 5.6 Hz, 1H), 8.74 (s, 1H), 8.12 (d, J = 5.6 Hz, 1H), 7.68 (d, J = 5.0 Hz, 1H), 7.35 - 7.31 (m, 3H), 7.27 (d, J = 3.5 Hz, 1H), 7.17 (t, J 50 = 8.8 Hz, 2H), 7.06 - 7.03 (m, 1H), 6.38 (s, 1H), 5.79 (d, J = 2.5 Hz, 1H), 4.84 - 4.74 (m, 2H), 4.56 - 4.52 (m, 1H), 4.49 (d, J = 5.6 Hz, 2H), 2.70 - 2.65 (m, 1H), 2.40 - 2.33 (m, 1H), 2.06 - 1.97 (m, 2H). LC / MS (ESI) m / z: 515 (M+H)+. RT (LC Method 1): 1.38 min. 1H NMR (400 MHz, DMSO-d6) δ 11.32 (s, 1H), 8.79 (t, J = 5.6 Hz, 1H), 8.74 (s, 1H), 8.25 (s, 1H), 8.11 (d, J = 5.6 Hz, 1H), 7.44 (s, 1H), 7.33 - 7.26 (m, 3H), 7.20 - 7.11 (m, 2H), 6.37 - 51 6.29 (m, 2H), 5.54 - 5.42 (m, 2H), 4.64 - 4.57 (m, 1H), 4.42 (d, J = 5.5 Hz, 2H), 2.77 - 2.65 (m, 1H), 2.44 - 2.33 (m, 1H), 2.10 - 1.96 (m, 2H). LC / MS (ESI) m / z: 500 (M+H)+. RT (LC Method 1): 1.13 min. 1H NMR (400 MHz, CD3OD) δ 8.98 (d, J = 2.0 Hz, 1H), 8.70 (s, 1H), 8.10 (d, J = 5.9 Hz, 1H), 8.04 (d, J = 2.0 Hz, 1H), 7.42 52 - 7.36 (m, 3H), 7.08 (t, J = 8.7 Hz, 2H), 6.48 (s, 1H), 5.12 (s, 2H), 4.59 - 4.56 (m, 1H), 4.54 (s, 2H), 2.90 - 2.82 (m, 1H), 2.65 - 2.57 (m, 1H), 2.21 - 2.05 (m, 2H). LC / MS (ESI) m / z: 516 (M+H)+. RT (LC Method 1): 1.11 min. 1H NMR (400 MHz, CD3OD) δ 8.73 (s, 1H), 8.11 (d, J = 5.9 Hz, 1H), 7.54 (d, J = 1.0 Hz, 1H), 7.43 - 7.37 (m, 3H), 7.07 (t, J = 8.8 Hz, 2H), 6.91 (d, J = 3.4 Hz, 1H), 6.56 (s, 1H), 6.54 - 54 6.51 (m, 1H), 4.97 (s, 2H), 4.61 (s, 2H), 4.58 - 4.54 (m, 1H), 2.88 - 2.79 (m, 1H), 2.63 - 2.55 (m, 1H), 2.22 - 2.14 (m, 1H), 2.11 - 2.02 (m, 1H). LC / MS (ESI) m / z: 499 (M+H)+. RT (LC Method 1): 1.28 min. 1H NMR (400 MHz, CH3OD) δ 8.99 (s, 1H), 8.95 (s, 1H), 8.31 (d, J = 5.5 Hz, 1H), 8.04 (s, 1H), 7.92 (d, J = 5.3 Hz, 1H), 7.42 77 - 7.38 (m, 3H), 7.07 (t, J = 8.3 Hz, 2H), 5.17 (s, 2H), 4.64 (s, 2H), 4.58 - 4.55 (m, 1H), 2.90 - 2.81 (m, 1H), 2.64 - 2.57 (m, 1H), 2.22 - 2.16 (m, 1H), 2.10 - 2.03 (m, 1H). LC / MS (ESI) m / z: 533 (M+H)+. RT (LC Method 1): 1.28 min. 1H NMR (400 MHz, DMSO-d6) δ 9.18 (d, J = 2.0 Hz, 1H), 8.75 (s, 1H), 8.58 (t, J = 5.5 Hz, 1H), 8.18 (d, J = 5.8 Hz, 1H), 8.11 (d, J = 2.0 Hz, 1H), 7.43 (d, J = 5.7 Hz, 1H), 7.36 - 7.32 (m, 84 2H), 7.16 (t, J = 8.8 Hz, 2H), 6.40 (s, 1H), 5.79 (s, 1H), 5.10 (s, 2H), 4.56 (s, 1H), 4.47 (d, J = 5.4 Hz, 2H), 3.64 (s, 3H), 2.74 - 2.66 (m, 1H), 2.43 - 2.34 (m, 1H), 2.07 - 1.99 (m, 2H). LC / MS (ESI) m / z: 530 (M+H)+. RT (LC Method 1): 1.20 min. ALXN-0780-PCT01-NP # Reactant A Reactant B Reactant C Characterization Data 1H NMR (400 MHz, CH3OD) 8.97 (d, J = 0.9 Hz, 1H), 8.33 (d, J = 5.7 Hz, 1H), 7.95 (d, J = 5.7 Hz, 1H), 7.61 - 7.55 (m, 1H), 7.44 (s, 1H), 7.42 - 7.37 (m, 2H), 7.33 - 7.30 (m, 1H), 7.11 -6 7.00 (m, 3H), 4.84 (s, 2H), 4.72 (s, 2H), 4.58 - 4.53 (m, 1H), 2.89 - 2.77 (m, 1H), 2.62 - 2.52 (m, 1H), 2.23 - 2.13 (m, 1H), 2.11 - 2.01 (m, 1H). LC / MS (ESI) (m / z): 532 (M+H)+. RT (LC Method 1): 1.00 min. 1H NMR (400 MHz, DMSO-d6) δ 8.81 (t, J = 5.5 Hz, 1H), 8.76 (s, 1H), 8.19 (d, J = 5.8 Hz, 1H), 7.71 - 7.67 (m, 1H), 7.46 (d, J = 5.8 Hz, 1H), 7.35 - 7.31 (m, 2H), 7.27 (d, J = 2.8 Hz, 1H),3 7.16 (t, J = 8.8 Hz, 2H), 7.07 - 7.04 (m, 1H), 6.49 (s, 1H), 5.78 (d, J = 2.3 Hz, 1H), 4.81 - 4.71 (m, 2H), 4.58 - 4.51 (m, 3H), 3.70 (s, 3H), 2.71 - 2.64 (m, 1H), 2.40 - 2.33 (m, 1H), 2.05 - 1.94 (m, 2H). LC / MS (ESI) (m / z): 529 (M+H)+. RT (LC Method 1): 1.44 min. 1H NMR (400 MHz, CD3OD) δ 8.76 (s, 1H), 8.13 (d, J = 6.0 Hz, 1H), 7.74 (d, J = 3.3 Hz, 1H), 7.58 (d, J = 3.3 Hz, 1H), 7.46 (d, J = 6.0 Hz, 1H), 7.40 - 7.37 (m, 2H), 7.08 (t, J = 8.8 Hz,4 2H), 6.60 (s, 1H), 5.73 (d, J = 3.2 Hz, 2H), 4.61 (s, 1H), 4.59 (s, 2H), 2.90 - 2.83 (m, 1H), 2.66 - 2.59 (m, 1H), 2.20 - 2.17 (m, 1H), 2.09 - 2.04 (m, 1H). LC / MS (ESI) m / z: 516 (M+H)+. RT (LC Method 1): 1.53 min. 1H NMR (400 MHz, DMSO-d6) δ 9.19 (d, J = 2.1 Hz, 1H), 9.03 (s, 1H), 8.83 (t, J = 5.9 Hz, 1H), 8.37 (d, J = 5.5 Hz, 1H), 8.11 (d, J = 2.1 Hz, 1H), 7.97 (d, J = 5.5 Hz, 1H), 7.71 (d, J = 8.201 Hz, 2H), 7.52 (d, J = 8.2 Hz, 2H), 7.32 (s, 1H), 6.03 (d, J = 2.6 Hz, 1H), 5.14 (s, 2H), 4.69 - 4.65 (m, 1H), 4.53 (d, J = 5.7 Hz, 2H), 2.73 - 2.66 (m, 1H), 2.40 - 2.33 (m, 1H), 2.12 - 2.02 (m, 2H). LC / MS (ESI) m / z: 583 (M+H)+. RT (LC Method 1): 1.59 min. 1H NMR (400 MHz, CD3OD) δ 8.98 (d, J = 2.1 Hz, 1H), 8.94 (s, 1H), 8.31 (d, J = 5.7 Hz, 1H), 8.03 (d, J = 2.1 Hz, 1H), 7.92 (d, J = 5.7 Hz, 1H), 7.38 (s, 1H), 7.27 - 7.23 (m, 2H), 7.18 -02 7.14 (m, 2H), 5.16 (s, 2H), 4.64 (s, 2H), 4.53 - 4.49 (m, 1H), 2.87 - 2.80 (m, 1H), 2.65 - 2.57 (m, 1H), 2.32 (s, 3H), 2.20 - 2.15 (m, 1H), 2.09 - 2.03 (m, 1H). LC / MS (ESI) (m / z): 529 (M+H)+. RT (LC Method 1): 1.41 min. 1H NMR (400 MHz, CD3OD) δ 9.00 (d, J = 1.9 Hz, 1H), 8.66 (s, 1H), 8.07 (d, J = 4.9 Hz, 1H), 8.02 (d, J = 2.0 Hz, 1H), 7.57 (s, 1H), 7.42 – 7.38 (m, 2H), 7.36 (d, J = 5.0 Hz, 1H), 7.07 (t, J03 = 8.7 Hz, 2H), 6.78 (s, 1H), 5.12 (s, 2H), 4.58 - 4.55 (m, 1H), 4.45 (s, 2H), 2.90 - 2.82 (m, 1H), 2.64 - 2.57 (m, 1H), 2.19 (s, 1H), 2.10 - 2.05 (m, 1H). LC / MS (ESI) m / z: 516 (M+H)+. RT (LC Method 1): 1.15 min. 1H NMR (400 MHz, CD3OD) δ 9.06 - 8.97 (m, 1H), 8.94 (s, 1H), 8.31 (d, J = 5.7 Hz, 1H), 8.02 (d, J = 2.0 Hz, 1H), 7.92 (d, J = 5.3 Hz, 1H), 7.42 - 7.36 (m, 3H), 7.10 - 7.03 (m, 2H), 5.35 -04 5.30 (m, 1H), 5.23 - 5.13 (m, 2H), 4.54 (d, J = 6.9 Hz, 1H), 2.89 - 2.79 (m, 1H), 2.64 - 2.55 (m, 1H), 2.21 - 2.14 (m, 1H), 2.09 - 2.02 (m, 1H), 1.61 (d, J = 7.0 Hz, 3H). LC / MS (ESI) m / z: 547 (M+H)+. RT (LC Method 1): 1.33 min. 1H NMR (400 MHz, CD3OD) δ 9.20 (s, 1H), 9.04 (d, J = 1.9 Hz, 1H), 8.46 (d, J = 6.0 Hz, 1H), 8.38 (d, J = 5.7 Hz, 1H), 8.05 (d, J = 2.1 Hz, 1H), 7.64 (s, 1H), 7.42 - 7.37 (m, 2H), 7.10 -10 7.05 (m, 2H), 5.37 - 5.34 (m, 1H), 5.23 - 5.15 (m, 2H), 4.59 - 4.52 (m, 1H), 2.90 - 2.80 (m, 1H), 2.65 - 2.57 (m, 1H), 2.20 - 2.17 (m, 2H), 1.66 (d, J = 7.1 Hz, 3H). LC / MS (ESI) m / z: 547 (M+H)+. RT (LC Method 1): 1.36 min. ALXN-0780-PCT01-NP Scheme 21. Synthesis of N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(6-(4-fluorophenyl)-4-oxo-2- (piperidin-1-yl)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetamide (Compound 42) (1.0 water (2 mL) were added K3PO4 (2.03 g, 9.57 mmol) and Pd(dtbpf)Cl2 (200 mg, 0.31 mmol) under N2 atmosphere and the reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was diluted with EtOAc, washed with water and brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 80% EtOAc in PE) to give the title compound (900 mg, yield 85.7%) as a yellow solid. LC / MS (ESI) m / z: 330 (M+H)+Step 2: Methyl 2-(2-chloro-6-(4-fluorophenyl)-4-oxopyrido[3,2-d]pyrimidin-3(4H)-yl)acetate To a solution of methyl 2-(6-(4-fluorophenyl)-2,4-dioxo-1,4-dihydropyrido[3,2-d]pyrimidin-3(2H)- yl)acetate (900 mg, 2.72 mmol) in POCl3 (10 mL) was added DIPEA (1.05 g, 8.18 mmol) under N2 atmosphere and the reaction mixture was stirred under N2atmosphere at 130 °C for 8 hours. The mixture was filtered, and the filtrate was concentrated to dryness to give the title compound (800 mg, yield 84.2%) as black oil, which was used directly in the next reaction without further purification. LC / MS (ESI) m / z: 348 (M+H)+. Step 3: Methyl 2-(6-(4-fluorophenyl)-4-oxo-2-(piperidin-1-yl)pyrido[3,2-d]pyrimidin-3(4H)-yl)acetate To a solution of methyl 2-(2-chloro-6-(4-fluorophenyl)-4-oxopyrido[3,2-d]pyrimidin-3(4H)-yl)acetate (200 mg, 0.57 mmol) in DMF (3 mL) was added DIPEA (148 mg, 1.15 mmol) and piperidine (146 mg, 1.72 mmol) and the reaction mixture was stirred at room temperature overnight. The mixture was diluted with water and extracted with EtOAc twice. The combined organic layers were washed with water and brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 40% EtOAc in PE) to give the title compound (120 mg, yield 52.6%) as a yellow solid. LC / MS (ESI) m / z: 397 (M+H)+. Step 4: Methyl 2-(6-(4-fluorophenyl)-4-oxo-2-(piperidin-1-yl)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)- yl)acetate To a solution of methyl 2-(6-(4-fluorophenyl)-4-oxo-2-(piperidin-1-yl)pyrido[3,2-d]pyrimidin-3(4H)- yl)acetate (120 mg, 0.30 mmol) in AcOH (2 mL) was added NaBH3CN (38 mg, 0.60 mmol), the mixture was degassed under N2 atmosphere for three times and stirred at 30 °C for 2 hours. The mixture was basified with 1N aq. NaOH to pH~9 and extracted with EtOAc twice. The combined organic layers were washed with water and brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness to give the title compound (100 mg, yield 82.6%) as a yellow oil. LC / MS (ESI) m / z: 401 (M+H)+. ALXN-0780-PCT01-NP Step 5: 2-(6-(4-Fluorophenyl)-4-oxo-2-(piperidin-1-yl)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetic acid To a solution of methyl 2-(6-(4-fluorophenyl)-4-oxo-2-(piperidin-1-yl)-5,6,7,8-tetrahydropyrido[3,2- d]pyrimidin-3(4H)-yl)acetate (100 mg, 0.25 mmol) in MeOH (2 mL) and water (1 mL) was added LiOH (15 mg, 0.37 mmol) and the mixture was stirred at room temperature overnight. The mixture was acidified with 1N aq. HCl to pH~3 and extracted with EtOAc twice. The combined organic layers were washed with water and brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to dryness to give the title compound (80 mg, yield 82.4%) as a white solid, which was used directly in the next reaction without further purification. LC / MS (ESI) m / z: 387 (M+H)+. Step 4: N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(6-(4-fluorophenyl)-4-oxo-2-(piperidin-1-yl)-5,6,7,8- tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetamide (Compound 42) To a mixture of 2-(6-(4-fluorophenyl)-4-oxo-2-(piperidin-1-yl)-5,6,7,8-tetrahydropyrido [3,2-d]pyrimidin- 3(4H)-yl)acetic acid (40 mg, 0.10 mmol) and (1H-pyrrolo[3,2-c]pyridin-2-yl)methanamine hydrochloride (27 mg, 0.16 mmol) in DMF (2 mL) were added DIPEA (83 mg, 0.65 mmol) and HATU (61 mg, 0.16 mmol), and the mixture was stirred at room temperature for 0.5 hour. The mixture was diluted with EtOAc, washed with water and brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 20% MeOH in DCM) and further purified by prep-HPLC to give Compound 42 (5.0 mg, yield 9.4%) as a white solid.1H NMR (400 MHz, CD3OD) δ 8.69 (s, 1H), 8.09 (d,J = 5.8 Hz, 1H), 7.44 - 7.35 (m, 3H), 7.10 - 7.00 (m, 2H), 6.57 (s, 1H), 4.92 - 4.89 (m, 2H), 4.62 (s, 2H), 4.46 - 4.33 (m, 1H), 2.99 - 2.91 (m, 4H), 2.85 - 2.69 (m, 1H), 2.62 - 2.47 (m, 1H), 2.19 - 2.09 (m, 1H), 2.04 - 1.97 (m, 1H), 1.60 - 1.51 (m, 6H). LC / MS (ESI) (m / z): 516 (M+H)+. RT (LC Method 1): 1.58 min. Compound 43 and Compound 44 were prepared according to the procedures above by replacing the piperidine with 1-methylpiperzine and morpholine, respectively. Compound 43:1H NMR (400 MHz, DMSO-d6) δ 11.36 (s, 1H), 8.86 - 8.78 (m, 1H), 8.72 (s, 1H), 8.11 (d, J = 5.6 Hz, 1H), 7.36 - 7.32 (m, 3H), 7.18 - 7.13 (m, 2H), 6.44 (s, 1H), 5.10 - 5.04 (m, 1H), 4.73 - 4.64 (m, 2H), 4.48 (d, J = 5.5 Hz, 2H), 4.42 - 4.38 (m, 1H), 2.90 - 2.85 (m, 4H), 2.77 - 2.58 (m, 4H), 2.36 - 2.31 (m, 2H), 2.12 (s, 3H), 2.02 - 1.91 (m, 2H). LC / MS (ESI) (m / z): 531 (M+H)+. RT (LC Method 1): 0.64 min. Compound 44:1H NMR (400 MHz, DMSO-d6) δ 11.32 (s, 1H), 8.82 (t, J = 5.5 Hz, 1H), 8.73 (s, 1H), 8.11 (d, J = 5.6 Hz, 1H), 7.36 - 7.32 (m, 3H), 7.16 (t, J = 8.8 Hz, 2H), 6.45 (s, 1H), 5.13 (s, 1H), 4.72 (d, J = 3.2 Hz, 2H), 4.48 (d, J = 5.6 Hz, 2H), 4.43 - 4.39 (m, 1H), 3.59 - 3.55 (m, 4H), 2.89 - 2.85 (m, 4H), 2.68 - 2.61 (m, 1H), 2.37 - 2.31 (m, 1H), 2.01 - 1.91 (m, 2H). LC / MS (ESI) m / z: 518 (M+H)+. RT (LC Method 1): 1.19 min. Compound 29 was also prepared according to the procedures above by replacing the (4- fluorophenyl)boronic acid with phenylboronic acid.1H NMR (400 MHz, DMSO-d6) δ 11.40 (s, 1H), 8.83 (s, 1H), 8.72 (s, 1H), 8.10 (d, J = 5.6 Hz, 1H), 7.35 - 7.31 (m, 5H), 7.28 - 7.24 (m, 1H), 6.43 (s, 1H), 4.68 (d, J = 2.7 Hz, 2H), 4.48 (d, J = 2.2 Hz, 2H), 4.43 - 4.34 (m, 1H), 2.86 - 2.78 (m, 4H), 2.71 - 2.65 (m, 1H), 2.63 - 2.58 (m, 1H), 2.39 - 2.29 (m, 1H), 2.02 - 1.93 (m, 1H), 1.55 - 1.48 (m, 4H), 1.44 (m, 2H). LC / MS (ESI) (m / z): 498 (M+H)+. RT (LC Method 1): 1.61 min. ALXN-0780-PCT01-NP Scheme 22. Synthesis of N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(4-oxo-6-(2-phenyloxazolidin-4- yl)pyrido[3,2-d]pyrimidin-3(4H)-yl)propanamide (Compound 48) (200 for three times and stirred under a H2balloon at 40 °C for 8 hours. The mixture was filtered, and the filtrate was concentrated to dryness. The residue was purified by prep-TLC (DCM: MeOH= 20: 1) to give the title compound (40 mg, yield 19.8%) as a yellow oil. LC / MS (ESI) m / z: 395 (M+H)+. Step 2: 2-(4-Oxo-6-(2-phenyloxazolidin-4-yl)pyrido[3,2-d]pyrimidin-3(4H)-yl) propanoic acid To a solution of ethyl 2-(4-oxo-6-(2-phenyloxazolidin-4-yl)pyrido[3,2-d]pyrimidin-3(4H)-yl)propanoate (40 mg, 0.10 mmol) in MeOH (2 mL) and water (1 mL) was added LiOH (7 mg, 0.30 mmol) and the mixture was stirred at room temperature for 2 hours. The mixture was acidified with 1N aq. HCl to pH~3 and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness to give the title compound (35 mg, yield 94.2%) as a yellow solid, which was used directly in the next reaction without further purification. LC / MS (ESI) m / z: 367 (M+H)+. Step 3: N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(4-oxo-6-(2-phenyloxazolidin-4-yl)pyrido[3,2-d]pyrimidin- 3(4H)-yl)propanamide (Compound 48) To a mixture of 2-(4-oxo-6-(2-phenyloxazolidin-4-yl)pyrido[3,2-d]pyrimidin-3(4H)-yl)propanoic acid (35 mg, 0.09 mmol) and (1H-pyrrolo[3,2-c]pyridin-2-yl) methanamine hydrochloride (26 mg, 0.14 mmol) in DMF (3 mL) was added DIPEA (62 mg, 0.48 mmol) and HATU (55 mg, 0.14 mmol) and the reaction mixture was stirred at room temperature for 1 hour. The mixture was concentrated under reduced pressure to dryness. The residue was purified by prep-TLC (DCM: MeOH= 8: 1) and further purified by prep-HPLC (C18, 20%-98% MeCN in water with 0.1% NH3.H2O) to give Compound 48 (2.6 mg, yield 5.5%) as a white solid.1H NMR (400 MHz, DMSO-d6) δ 11.33 - 11.29 (m, 1H), 8.72 - 8.70 (m, 1H), 8.61 - 8.56 (m, 1H), 8.11 - 8.08 (m, 1H), 7.94 - 7.91 (m, 2H), 7.57 (t, J = 7.0 Hz, 1H), 7.52 - 7.48 (m, 2H), 7.37 - 7.34 (m, 1H), 7.31 - 7.29 (m, 1H), 7.24 (d, J = 8.4 Hz, 1H), 6.95 - 6.93 (m, 1H), 6.38 - 6.36 (m, 1H), 5.45 - 5.40 (m, 1H), 5.15 - 5.10 (m, 1H), 4.82 - 4.77 (m, 1H), 4.71 - 4.64 (m, 2H), 4.61 - 4.56 (m, 1H), 4.45 - 4.41 (m, 2H), 1.41 - 1.37 (m, 3H). LC / MS (ESI) m / z: 496 (M+H)+. RT (LC Method 1): 0.88 min.

[0003] ALXN-0780-PCT01-NP Scheme 23. Synthesis of N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(6-(4-fluorophenyl)-4-oxo-2- (piperazin-1-yl)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetamide (Compound 49) OOOF O OOFO OOFH N NaBH CN N LiOH N N N N DMF AcOH MeOH, H O 2- DIPEA (397 mg, 2.30 mmol) under N2atmosphere and the mixture was stirred at room temperature for 16 hours. The mixture was diluted with EtOAc, washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 50% EtOAc in PE) to give the title compound (160 mg, yield 55.9%) as a yellow solid. LC / MS (ESI) m / z: 498 (M+H)+. Step 2: tert-Butyl 4-(6-(4-fluorophenyl)-3-(2-methoxy-2-oxoethyl)-4-oxo-3,4,5,6,7,8-hexahydropyrido[3,2- d]pyrimidin-2-yl)piperazine-1-carboxylate To a solution of tert-butyl 4-(6-(4-fluorophenyl)-3-(2-methoxy-2-oxoethyl)-4-oxo-3,4-dihydropyrido[3,2- d]pyrimidin-2-yl)piperazine-1-carboxylate (120 mg, 0.24 mmol) in AcOH (3 mL) was added NaBH3CN (76 mg, 1.21 mmol) and the reaction mixture was stirred at room temperature for 3 hours. The mixture was basified with saturated aq. Na2CO3solution to pH~8 and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to dryness to give to give the title compound (100 mg, yield 82.6%) as a yellow solid, which was used directly in the next reaction without further purification. LC / MS (ESI) m / z: 502 (M+H)+. Step 3: 2-(2-(4-(tert-Butoxycarbonyl)piperazin-1-yl)-6-(4-fluorophenyl)-4-oxo-5,6,7,8-tetrahydropyrido[3,2- d]pyrimidin-3(4H)-yl)acetic acid To a solution of tert-butyl 4-(6-(4-fluorophenyl)-3-(2-methoxy-2-oxoethyl)-4-oxo-3,4,5,6,7,8- hexahydropyrido[3,2-d]pyrimidin-2-yl)piperazine-1-carboxylate (100 mg, 0.20 mmol) in MeOH (2 mL) and water (1 mL) was added LiOH (24 mg, 1.0 mmol) and the mixture was stirred at room temperature for 2 hours. The mixture was acidified with 1N aq. HCl to pH~3 and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to dryness to give the title compound (90 mg, yield 92.5%) as a yellow solid, which was used directly in the next reaction without further purification. LC / MS (ESI) m / z: 488 (M+H)+. ALXN-0780-PCT01-NP Step 4: tert-Butyl 4-(3-(2-(((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)amino)-2-oxoethyl)-6-(4-fluorophenyl)-4-oxo- 3,4,5,6,7,8-hexahydropyrido[3,2-d]pyrimidin-2-yl)piperazine-1-carboxylate To a mixture of 2-(2-(4-(tert-butoxycarbonyl)piperazin-1-yl)-6-(4-fluorophenyl)-4-oxo-5,6,7,8- tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetic acid (90 mg, 0.18 mmol) and (1H-pyrrolo[3,2-c]pyridin-2- yl)methanamine hydrochloride (51 mg, 0.28 mmol) in DMF (3 mL) was added DIPEA (119 mg, 0.92 mmol) and HATU (125 mg, 0.28 mmol), and the reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with EtOAc, washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to dryness. The residue was purified by prep-TLC (DCM: MeOH= 15: 1) to give the title compound (40 mg, yield 35.1%) as a yellow oil. LC / MS (ESI) m / z: 617 (M+H)+. Step 5: N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(6-(4-fluorophenyl)-4-oxo-2-(piperazin-1-yl)-5,6,7,8- tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetamide (Compound 49) A solution of tert-butyl 4-(3-(2-(((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)amino)-2-oxoethyl)-6-(4- fluorophenyl)-4-oxo-3,4,5,6,7,8-hexahydropyrido[3,2-d]pyrimidin-2-yl)piperazine-1-carboxylate (40.0 mg, 0.06 mmol) in DCM (1 mL) and HCl / 1,4-dioxane (2 mL, 4M) was stirred under N2atmosphere at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure to dryness and further purified by prep-HPLC (C18, 20%-98% MeCN in water with 0.1% FA) to give Compound 49 (4.0 mg, yield 11.9%) as a white solid.1H NMR (400 MHz, CD3OD) δ 8.91 (s, 1H), 8.22 (d, J = 5.7 Hz, 1H), 7.71 (d, J = 6.2 Hz, 1H), 7.40 - 7.35 (m, 2H), 7.06 (t, J = 8.8 Hz, 2H), 6.85 (s, 1H), 4.88 (s, 2H), 4.69 (s, 2H), 4.46 - 4.41 (m, 1H), 3.27 (s, 8H), 2.82 - 2.74 (m, 1H), 2.56 - 2.49 (m, 1H), 2.18 - 2.11 (m, 1H), 2.05 - 1.99 (m, 1H). LC / MS (ESI) m / z: 517 (M+H)+. RT (LC Method 1): 0.59 min. Scheme 24. Synthesis of (2R)-N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(4-oxo-6-(2-phenyloxazolidin- 5-yl)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)propanamide (Compound 55) (500 mg, 1.28 mmol) and 2-phenyl-5-(tributylstannyl)oxazole (1.12 g, 2.58 mmol) in DMF (5 mL) was added Pd(PPh3)4(149 mg, 0.13 mmol) under N2atmosphere, the reaction mixture was degassed under N2atmosphere for three times and stirred at 80 °C overnight. The mixture was quenched with saturated aq. KF solution and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 92% EtOAc in PE) to give the title compound (400 mg, yield 68.6%) as a yellow solid. LC / MS (ESI) m / z: 453 (M+H)+. ALXN-0780-PCT01-NP Step 2: Benzyl (2R)-2-(4-oxo-6-(2-phenyloxazolidin-5-yl)-5,6,7,8-tetrahydropyrido [3,2-d]pyrimidin-3(4H)- yl)propanoate To a solution of benzyl (R)-2-(4-oxo-6-(2-phenyloxazol-5-yl)pyrido[3,2-d]pyrimidin-3(4H)- yl)propanoate (400 mg, 0.88 mmol) in AcOH (5 mL) was added PtO2(20 mg), the reaction mixture was degassed under N2atmosphere for three times and stirred under a H2balloon at 30 °C for 4 hours. The mixture was filtered, and the filtrate was concentrated to dryness. The residue was purified by prep-HPLC to give the title compound (150 mg, yield 36.8%) as a yellow oil. LC / MS (ESI) m / z: 461 (M+H)+. Step 3: (2R)-2-(4-oxo-6-(2-phenyloxazolidin-5-yl)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)propanoic acid To a solution of benzyl (2R)-2-(4-oxo-6-(2-phenyloxazolidin-5-yl)-5,6,7,8-tetrahydropyrido[3,2- d]pyrimidin-3(4H)-yl)propanoate (150 mg, 0.32 mmol) in MeOH / water (4.0 mL, v / v= 4 / 1) was added LiOH^H2O (27 mg, 0.64 mmol) and the reaction mixture was stirred at room temperature for 1 hour. The mixture was acidified with 1N aq. HCl to pH~3 and extracted with EtOAc twice. The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness to give the title compound (110 mg, yield 91.6%) as a yellow solid, which was used directly in the next step without further purification. LC / MS (ESI) m / z: 371 (M+H)+. Step 4: (2R)-N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(4-oxo-6-(2-phenyloxazolidin-5-yl)-5,6,7,8- tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)propanamide (Compound 55) To a mixture of (2R)-2-(4-oxo-6-(2-phenyloxazolidin-5-yl)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin- 3(4H)-yl)propanoic acid (110 mg, 0.29 mmol) and (1H-pyrrolo[3,2-c]pyridin-2-yl)methanamine hydrochloride (80 mg, 0.44 mmol) in DMF (5 mL) was added DIPEA (187 mg, 1.45 mmol) and HATU (132 mg, 0.34 mmol) and the reaction mixture was stirred at room temperature for 1 hour. The mixture was concentrated under reduced pressure to dryness. The residue was purified by prep-HPLC (C18, 40 - 95% MeCN in water with 0.1% NH3.H2O) to give Compound 55 (24.2 mg, yield 16.3%) as a white solid.1H NMR (400 MHz, CD3OD) δ 8.69 (s, 1H), 8.09 (d, J = 5.8 Hz, 1H), 7.88 (s, 1H), 7.83 (d, J = 7.4 Hz, 2H), 7.52 (d, J = 6.9 Hz, 1H), 7.48 - 7.42 (m, 3H), 6.54 (s, 1H), 5.36 (d, J = 7.3 Hz, 1H), 4.67 - 4.56 (m, 2H), 3.71 - 3.61 (m, 1H), 3.52 - 3.46 (m, 1H), 3.44 - 3.38 (m, 1H), 2.73 (s, 2H), 2.06 (s, 1H), 1.87 - 1.76 (m, 3H), 1.74 (d, J = 7.3 Hz, 3H). LC / MS (ESI) m / z: 500 (M+H)+. RT (LC Method 1): 0.69 min. Scheme 25. Synthesis of (2R)-N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(6-(2-cyclohexyloxazolidin-5- yl)-4-oxo-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)propanamide (Compound 56) (500 mg, 1.28 mmol) and 2-phenyl-5-(tributylstannyl)oxazole (1.12 g, 2.58 mmol) in DMF (5 mL) was added Pd(PPh3)4(149 ALXN-0780-PCT01-NP mg, 0.13 mmol) under N2 atmosphere and the reaction mixture was degassed under N2 atmosphere for three times and stirred at 80 °C overnight. The mixture was quenched with saturated aq. KF solution and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 92% EtOAc in PE) to give the title compound (400 mg, yield 68.6%) as a yellow solid. LC / MS (ESI) m / z: 453 (M+H)+. Step 2: Benzyl (2R)-2-(6-(2-cyclohexyloxazolidin-5-yl)-4-oxo-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)- yl)propanoate To a solution of benzyl (R)-2-(4-oxo-6-(2-phenyloxazol-5-yl)pyrido[3,2-d]pyrimidin-3(4H)- yl)propanoate (400 mg, 0.88 mmol) in AcOH (5 mL) was added PtO2 (20 mg), the reaction mixture was degassed under N2 atmosphere for three times and stirred under a H2 balloon at 30 °C for 4 hours. The mixture was filtered, and the filtrate was concentrated to dryness. The residue was purified by prep-HPLC to give the title compound (50 mg, yield 12.4%) as a yellow oil. LC / MS (ESI) m / z: 467 (M+H)+. Step 3: (2R)-2-(6-(2-cyclohexyloxazolidin-5-yl)-4-oxo-5,6,7,8-tetrahydropyrido[3,2-d] pyrimidin-3(4H)- yl)propanoic acid To a solution of benzyl (2R)-2-(6-(2-cyclohexyloxazolidin-5-yl)-4-oxo-5,6,7,8-tetrahydropyrido[3,2- d]pyrimidin-3(4H)-yl)propanoate (50 mg, 0.10 mmol) in MeOH / water (4.0 mL, v / v= 4 / 1) was added LiOH^H2O (9 mg, 0.21 mmol) and the reaction mixture was stirred at room temperature for 1 hour. The mixture was acidified with 1N aq. HCl to pH~3 and extracted with EtOAc twice. The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness to give the title compound (30 mg, yield 73.8%) as a yellow solid, which was used directly in the next reaction without further purification. LC / MS (ESI) m / z: 377 (M+H)+. Step 4: (2R)-N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(6-(2-cyclohexyloxazolidin-5-yl)-4-oxo-5,6,7,8- tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)propanamide (Compound 56) To a mixture of (2R)-2-(6-(2-cyclohexyloxazolidin-5-yl)-4-oxo-5,6,7,8-tetrahydropyrido [3,2- d]pyrimidin-3(4H)-yl)propanoic acid (30 mg, 0.079 mmol) and (1H-pyrrolo[3,2-c]pyridin-2-yl)methanamine hydrochloride (21 mg, 0.11 mmol) in DMF (2 mL) was added DIPEA (51 mg, 0.39 mmol) and HATU (45 mg, 0.11 mmol) and the reaction mixture was stirred at room temperature for 1 hour. The mixture was concentrated under reduced pressure to dryness. The residue was purified by prep-HPLC (C18, 40-95% MeCN in water with 0.1% NH3.H2O) to give Compound 56 (4.3 mg, yield 10.7%) as a white solid.1H NMR (400 MHz, CH3OD) δ 8.69 (s, 1H), 8.09 (d, J = 5.8 Hz, 1H), 7.85 (s, 1H), 7.42 (d, J = 5.8 Hz, 1H), 6.52 (s, 1H), 5.39 - 5.28 (m, 1H), 4.59 (d, J = 17.1 Hz, 2H), 3.45 - 3.36 (m, 1H), 3.26 - 3.20 (m, 1H), 3.02 - 2.93 (m, 2H), 2.74 - 2.62 (m, 2H), 2.19 - 2.11 (m, 1H), 2.04 - 1.99 (m, 1H), 1.81 - 1.73 (m, 5H), 1.72 (d, J = 7.3 Hz, 3H), 1.70 - 1.60 (m, 3H), 1.47 - 1.38 (m, 2H), 1.32 - 1.26 (m, 2H). LC / MS (ESI) m / z: 506 (M+H)+. RT (LC Method 1): 0.91 min. ALXN-0780-PCT01-NP Scheme 26. Synthesis of 2-(4-oxo-6-(2-phenyloxazol-5-yl)-5,6,7,8-tetrahydropyrido [3,2-d]pyrimidin- 3(4H)-yl)-N-((4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)methyl)acetamide (Compound 57) g, 3.14 mmol) under N2 atmosphere, the reaction mixture was degassed under N2 atmosphere for three times and stirred at 110 °C overnight. The mixture was diluted with water and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 50% EtOAc in PE) to give the title compound (700 mg, yield 84.3%) as a yellow solid. LC / MS (ESI) m / z: 265 (M+H)+. Step 2: tert-Butyl 2-(aminomethyl)-6,7-dihydrothieno[3,2-c]pyridine-5(4H)-carboxylate To a solution of tert-butyl 2-cyano-6,7-dihydrothieno[3,2-c]pyridine-5(4H)-carboxylate (100 mg, 0.38 mmol) in EtOH (2 mL) was added Raney Ni (5 mg), the mixture was degassed under N2 atmosphere for three times and stirred under a H2 balloon at 50 °C overnight. The mixture was filtered, and the filtrate was concentrated to dryness to give the title compound (50 mg, yield 49.2%) as a yellow solid, which was used directly in the next reaction without further purification. LC / MS (ESI) m / z: 269 (M+H)+. Step 3: tert-Butyl 2-((2-(4-oxo-6-(2-phenyloxazol-5-yl)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)- yl)acetamido)methyl)-6,7-dihydrothieno[3,2-c]pyridine-5(4H)-carboxylate To a mixture of 2-(4-oxo-6-(2-phenyloxazol-5-yl)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)- yl)acetic acid (24 mg, 0.068 mmol) and tert-butyl 2-(aminomethyl)-6,7-dihydrothieno[3,2-c]pyridine-5(4H)- carboxylate (27 mg, 0.10 mmol) in DMF (2 mL) was added DIPEA (53 mg, 0.41 mmol) and HATU (28 mg, 0.075 mmol) under N2atmosphere and the mixture was stirred at room temperature for 1 hour. The mixture was diluted with EtOAc, washed with saturated aq. NaHCO3 solution and brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 50% EtOAc in PE) to give the title compound (30 mg, yield 73.1%) as a white solid. LC / MS (ESI) m / z: 603 (M+H)+. Step 4: 2-(4-Oxo-6-(2-phenyloxazol-5-yl)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)-N-((4,5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)methyl)acetamide (Compound 57) To a solution of tert-butyl 2-((2-(4-oxo-6-(2-phenyloxazol-5-yl)-5,6,7,8-tetrahydropyrido[3,2- d]pyrimidin-3(4H)-yl)acetamido)methyl)-6,7-dihydrothieno[3,2-c]pyridine-5(4H)-carboxylate (30 mg, 0.050 mmol) in DCM (1 mL) was added HCl / 1,4-dioxane (1 mL) and the reaction mixture was stirred at room temperature for 0.5 hour. The mixture was concentrated under reduced pressure to dryness. The residue was purified by prep-HPLC (C18, 40-65% MeCN in water with 0.1% NH3.H2O) to give Compound 57 (4.0 mg, yield ALXN-0780-PCT01-NP 16.0%) as a white solid.1H NMR (400 MHz, DMSO-d6) δ 8.76 (t, J = 5.7 Hz, 1H), 7.99 - 7.90 (m, 2H), 7.75 (s, 1H), 7.54 - 7.48 (m, 3H), 7.07 (s, 1H), 6.62 (s, 1H), 5.72 (d, J = 2.5 Hz, 1H), 4.73 - 4.67 (m, 1H), 4.62 - 4.51 (m, 2H), 4.35 (d, J = 5.6 Hz, 2H), 3.64 (s, 2H), 2.91 (t, J = 5.6 Hz, 2H), 2.72 - 2.66 (m, 1H), 2.65 - 2.52 (m, 4H), 2.25 - 2.17 (m, 1H), 2.16 - 2.09 (m, 1H). LC / MS (ESI) m / z: 503 (M+H)+. RT (LC Method 1): 0.99 min. Scheme 27. Synthesis of 3-(2-(((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)amino)-2-oxoethyl)-N- cyclopentyl-4-oxo-3,4,5,6,7,8-hexahydropyrido[3,2-d]pyrimidine-6-carboxamide (Compound 58) (4.50 g, and the mixture was stirred at room temperature for 10 hours. The mixture was diluted with water and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 35% EtOAc in PE) to give the title compound (5.00 g, yield 54.9%) as a white solid. LC / MS (ESI) m / z: 330 (M+H)+. Step 2: tert-Butyl 2-(6-bromo-4-oxopyrido[3,2-d]pyrimidin-3(4H)-yl)acetate To a solution of tert-butyl (3-amino-6-bromopicolinoyl)glycinate (1.10 g, 334 mmol) in triethoxymethane (10 mL) and TFA (2 mL) at 0 °C and the reaction solution was stirred at 25 °C for 6 hours. The mixture was acidified with saturated aq. NaHCO3 solution to pH~7 and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated to give the title compound (1.1 g, yield 93.8%) as a yellow solid. LC / MS (ESI) (m / z): 340 (M+H)+. Step 3: Methyl 3-(2-(tert-butoxy)-2-oxoethyl)-4-oxo-3,4-dihydropyrido[3,2-d] pyrimidine-6-carboxylate To a solution of tert-butyl 2-(6-bromo-4-oxopyrido[3,2-d]pyrimidin-3(4H)-yl)acetate (1.00 g, 2.94 mmol) in MeOH (8 mL) and DMSO (4 mL) was added TEA (0.9 g, 8.90 mmol) and Pd(dppf)Cl2(220 mg, 0.30 mmol) at 25 °C under N2atmosphere and the reaction mixture was degassed under N2atmosphere for three times and stirred at 85 °C overnight. The mixture was diluted with water and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 50% EtOAc in PE) to give the title compound (300 g, yield 33.3%) as a yellow oil. LC / MS (ESI) m / z: 320 (M+H)+. ALXN-0780-PCT01-NP Step 4: Methyl 3-(2-(tert-butoxy)-2-oxoethyl)-4-oxo-3,4,5,6,7,8-hexahydropyrido [3,2-d]pyrimidine-6- carboxylate To a solution of methyl 3-(2-(tert-butoxy)-2-oxoethyl)-4-oxo-3,4-dihydropyrido[3,2-d]pyrimidine-6- carboxylate (300 mg, 3.71 mmol) in AcOH (5 mL) was added PtO2(36.2 mg, 0.15 mmol). The mixture was degassed under N2atmosphere for three times and stirred under a H2balloon at room temperature for 12 hours. The mixture was filtered, and the filtrate was concentrated to dryness to give the title compound (300 mg, yield 99.9%) as a yellow solid, which was used directly in the next step without further purification. LC / MS (ESI) m / z: 324 (M+H)+. Step 5: 3-(2-(tert-Butoxy)-2-oxoethyl)-4-oxo-3,4,5,6,7,8-hexahydropyrido[3,2-d]pyrimidine-6-carboxylic acid To a solution of methyl 3-(2-(tert-butoxy)-2-oxoethyl)-4-oxo-3,4,5,6,7,8-hexahydropyrido[3,2- d]pyrimidine-6-carboxylate (300.0 mg, 0.91 mmol) in MeOH (3.0 mL) and water (0.5 mL) was added LiOH.H2O (117 mg, 2.70 mmol) and the mixture was stirred at 50 °C for 1 hour. The mixture was acidified with 1N aq. HCl to pH~3 and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated to give the title compound (300 mg, yield 99.9%) as a white solid, which was used directly in the next reaction without further purification. LC / MS (ESI) (m / z): 310 (M+H)+. Step 6: tert-Butyl 2-(6-(cyclopentylcarbamoyl)-4-oxo-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetate To a mixture of 3-(2-(tert-butoxy)-2-oxoethyl)-4-oxo-3,4,5,6,7,8-hexahydropyrido[3,2-d]pyrimidine-6- carboxylic acid (100 mg, 0.323 mmol) and cyclopentanamine (41.0 mg, 0.482 mmol) in MeCN (3 mL) was added TCFH (272 mg, 0.970 mmol) and NMI (160 mg, 1.95 mmol) at 0 °C and the mixture was stirred at room temperature for 8 hours. The mixture was diluted with water and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to dryness. The residue was purified by prep-TLC (DCM: MeOH= 5: 1) to give the title compound (105 mg, yield 86.7%) as a yellow oil. LC / MS (ESI) m / z: 377 (M+H)+. Step 7: 2-(6-(Cyclopentylcarbamoyl)-4-oxo-5,6,7,8-tetrahydropyrido[3,2-d] pyrimidin-3(4H)-yl)acetic acid To a mixture of tert-butyl 2-(6-(cyclopentylcarbamoyl)-4-oxo-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin- 3(4H)-yl)acetate (105 mg, 0.27 mmol) in DCM (3.0 mL) was added TFA (0.5 mL) and the mixture was stirred at 25 °C for 0.3 hours. The mixture was filtered, and the filtrate was concentrated to dryness to give the title compound (75 mg, yield 84.2%) as a yellow solid, which was used directly in the next reaction without further purification. LC / MS (ESI) m / z: 321 (M+H)+. Step 8: 3-(2-(((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)amino)-2-oxoethyl)-N-cyclopentyl-4-oxo-3,4,5,6,7,8- hexahydropyrido[3,2-d]pyrimidine-6-carboxamide (Compound 58) To a mixture of 2-(6-(cyclopentylcarbamoyl)-4-oxo-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)- yl)acetic acid (75 mg, 0.23 mmol) and (1H-pyrrolo[3,2-c]pyridin-2-yl)methanamine hydrochloride (33 mg, 0.35 mmol) in DMF (3 mL) was added DIPEA (90 mg, 0.69 mmol) and HATU (105 mg, 0.27 mmol), and the mixture was stirred at room temperature for 1 hour. The mixture was diluted with EtOAc, washed with water and brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to dryness. The residue was purified by prep-TLC (DCM: MeOH= 5: 1) and further purified by prep-HPLC (C18, 20%-95% MeCN In water with 0.1% FA) to give Compound 58 (5 mg, yield 6.6%) as a white solid.1H NMR (400 MHz, ALXN-0780-PCT01-NP CD3OD) δ 8.91 (s, 1H), 8.44 (s, 1H), 8.23 (d, J = 6.2 Hz, 1H), 7.82 (s, 1H), 7.72 (d, J = 5.7 Hz, 1H), 6.83 (s, 1H), 4.75 (s, 2H), 4.68 (s, 2H), 4.15 - 4.11 (m, 1H), 3.98 (d, J = 4.9 Hz, 1H), 2.71 - 2.66 (m, 1H), 2.61 - 2.55 (m, 1H), 2.21 - 2.16 (m, 1H), 1.99 - 1.89 (m, 3H), 1.72 - 1.67 (m, 2H), 1.61 - 1.56 (m, 2H), 1.50 - 1.42 (m, 2H). LC / MS (ESI) (m / z): 450 (M+H)+. RT (LC Method 1): 0.37 min. Scheme 28. Synthesis of methyl 2-(6-(4-fluorophenyl)-4-oxo-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin- 3(4H)-yl)acetate (Compound 59) To a solution -yl)acetate (50 mg, 0.16 mmol) in THF (2 mL) was added PtO2(7 mg, 0.032 mmol) and AcOH (0.1 mL), the mixture was degassed under N2 atmosphere for three times and stirred under a H2 balloon at 60 °C overnight. The mixture was filtered, and the filtrate was concentrated under reduced pressure to dryness. The residue was purified by prep-HPLC (C18, 30-98% MeCN in water with 0.1% NH3.H2O) to give Compound 59 (6.0 mg, yield 11.8%) as a white solid.1H NMR (400 MHz, CD3OD) δ 7.79 (s, 1H), 7.40 - 7.34 (m, 2H), 7.07 (t, J = 8.8 Hz, 2H), 4.78 (s, 2H), 4.51 - 4.45 (m, 1H), 3.78 (s, 3H), 2.87 - 2.77 (m, 1H), 2.61 - 2.52 (m, 1H), 2.18 - 2.10 (m, 1H), 2.07 - 1.98 (m, 1H). LC / MS (ESI) m / z: 318 (M+H)+. RT (LC Method 1): 1.51 min. Scheme 29. Synthesis of 2-(6-(4-fluorophenyl)-4-oxo-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)- yl)-N-((1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)acetamide (Compound 60) To a tert- 2- mg, 1.21 1,4-dioxane (5 mL) was added t-BuONa (350 mg, 3.6 mmol) at room temperature. After stirred for 15 minutes, methyl benzenesulfonate (208 mg, 1.21 mmol) was added to the reaction solution and the mixture was stirred at room temperature for 3 hours. The mixture was filtered, and the filtrate was concentrated under reduced pressure to dryness. The reside was purified by prep-HPLC (C18, 20%-95% MeCN in water with 0.1% TFA) to give the title compound (140 mg, yield 44%) as a yellow solid. LC / MS (ESI) m / z: 262 (M+H)+. Step 2: (1-Methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)methanamine hydrochloride To a solution of tert-butyl ((1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)carbamate (50 mg, 0.19 mmol) in DCM (1 mL) was added HCl / 1,4-dioxane (1 mL) at room temperature, and the reaction mixture was concentrated under reduced pressure to give the title compound (25 mg, yield 83%) as a yellow solid, which was used directly in the next reaction without further purification. LC / MS (ESI) m / z: 162 (M+H)+. ALXN-0780-PCT01-NP Step 3: 2-(6-(4-Fluorophenyl)-4-oxo-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)-N-((1-methyl-1H- pyrrolo[3,2-c]pyridin-2-yl)methyl)acetamide (Compound 60) To a mixture of 2-(6-(4-fluorophenyl)-4-oxo-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetic acid (40 mg, 0.13 mmol) and (1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)methanamine hydrochloride (21 mg, 0.13 mmol) in DMF (1.5 mL) was added DIPEA (50 mg, 0.39 mmol) and HATU (60 mg, 0.16 mmol), and the reaction mixture was stirred at room temperature for 1 hour. The mixture was diluted with EtOAc, washed with water and brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness. The residue was purified by prep-HPLC (C18, 30-98% MeCN in water with 0.1% NH3.H2O) to give Compound 60 (4 mg, yield 7%) as a white solid.1H NMR (400 MHz, CD3OD) δ 8.70 (s, 1H), 8.15 (d, J = 5.9 Hz, 1H), 7.80 (s, 1H), 7.43 (d, J = 5.9 Hz, 1H), 7.40 - 7.34 (m, 2H), 7.06 (t, J = 8.7 Hz, 2H), 6.66 (s, 1H), 4.71 (s, 2H), 4.68 (s, 2H), 4.50 - 4.45 (m, 1H), 3.78 (s, 3H), 2.88 - 2.75 (m, 1H), 2.61 - 2.50 (m, 1H), 2.17 - 1.98 (m, 2H). LC / MS (ESI) m / z: 447 (M+H)+. RT (LC Method 1): 0.94 min. Scheme 30. Synthesis of 2-(4-oxo-6-(2-phenyloxazol-5-yl)-5,6,7,8-tetrahydropyrido [3,2-d]pyrimidin- 3(4H)-yl)-N-((4,5,6,7-tetrahydrothieno[2,3-c]pyridin-2-yl)methyl) acetamide (Compound 62) in at room temperature for 2 hours. The mixture was diluted with water and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 – 10% EtOAc in PE) to give the title compound (1 g, yield 75.5%) as a yellow solid. LC / MS (ESI) m / z: 318 (M+H)+. Step 2: tert-Butyl 2-cyano-4,7-dihydrothieno[2,3-c]pyridine-6(5H)-carboxylate To a solution of tert-butyl 2-bromo-4,7-dihydrothieno[2,3-c]pyridine-6(5H)-carboxylate (1 g, 3.15 mmol) in DMF (10 mL) was added Zn(CN)2 (738 mg, 6.30 mmol) and Pd(PPh3)4 (370 mg, 0.32 mmol), and the reaction mixture was degassed under N2 atmosphere for three times and stirred at 110 °C for 16 hours. The mixture was diluted with water and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 20% EtOAc in PE) to give the title compound (600 mg, yield 72%) as a yellow solid. LC / MS (ESI) m / z: 265 (M+H)+. Step 3: tert-Butyl 2-(aminomethyl)-4,7-dihydrothieno[2,3-c]pyridine-6(5H)-carboxylate To a solution of tert-butyl 2-cyano-4,7-dihydrothieno[2,3-c]pyridine-6(5H)-carboxylate (200 mg, 0.76 mmol) in EtOH (4.0 mL) was added Raney Ni (20 mg), the reaction mixture was degassed under N2 atmosphere for three times and stirred under a H2balloon at room temperature overnight. The mixture was ALXN-0780-PCT01-NP filtered, and the filtrate was concentrated under reduced pressure to dryness. The residue was purified by prep-TLC (DCM: MeOH= 30: 1) to give the title compound (25 mg, yield 12.3%) as a yellow solid. LC / MS (ESI) m / z: 269 (M+H)+. Step 4: tert-Butyl 2-((2-(4-oxo-6-(2-phenyloxazol-5-yl)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)- yl)acetamido)methyl)-4,7-dihydrothieno[2,3-c]pyridine-6(5H)-carboxylate To a mixture of tert-butyl 2-(aminomethyl)-4,7-dihydrothieno[2,3-c]pyridine-6(5H)-carboxylate (25 mg, 0.09 mmol) and 2-(4-oxo-6-(2-phenyloxazol-5-yl)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetic acid (32 mg, 0.09 mmol) in DMF (1 mL) was added DIPEA (35 mg, 0.27 mmol) and HATU (41 mg, 0.11 mmol), and the reaction mixture was stirred at room temperature for 1 hour. The mixture was concentrated under reduced pressure to dryness. The residue was purified by prep-TLC (DCM: MeOH= 10: 1) to give the title compound (20 mg, yield 37%) as a yellow solid, which was used directly in the next reaction without further purification. LC / MS (ESI) m / z: 603 (M+H)+. Step 5: 2-(4-oxo-6-(2-phenyloxazol-5-yl)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)-N-((4,5,6,7- tetrahydrothieno[2,3-c]pyridin-2-yl)methyl)acetamide (Compound 62) To a solution of tert-butyl 2-((2-(4-oxo-6-(2-phenyloxazol-5-yl)-5,6,7,8-tetrahydropyrido[3,2- d]pyrimidin-3(4H)-yl)acetamido)methyl)-4,7-dihydrothieno[2,3-c]pyridine-6(5H)-carboxylate (20 mg, 0.03 mmol) in DCM (1 mL) was added HCl / 1,4-dioxane (0.5 mL), and the reaction mixture was stirred at room temperature for 1 hour. The mixture was concentrated under reduced pressure to dryness. The residue was purified by prep-HPLC (C18, 65-95% MeCN in water with 0.1% NH3.H2O) to give Compound 62 (2 mg, yield 13.3%) as a white solid.1H NMR (400 MHz, CD3OD) δ 8.50 (s, 1H), 8.01 - 7.95 (m, 2H), 7.79 (s, 1H), 7.53 - 7.47 (m, 3H), 7.09 (s, 1H), 6.80 (s, 1H), 4.80 - 4.78 (m, 1H), 4.68 (s, 2H), 4.51 (s, 2H), 4.28 (s, 2H), 3.40 (t, J = 6.1 Hz, 2H), 2.92 - 2.85 (m, 2H), 2.85 - 2.77 (m, 1H), 2.74 - 2.63 (m, 1H), 2.39 - 2.24 (m, 2H). LC / MS (ESI) m / z: 503 (M+H)+. RT (LC Method 1): 1.05 min. Scheme 31. Synthesis of N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(6-(4-fluorophenyl)-4-oxo-5,6,7,8- tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)-N-methylacetamide (Compound 64) acid (30 mg, 0.10 mmol) and N-methyl-1-(1-(phenylsulfonyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)methanamine (36 mg, 0.12 mmol) in DMF (2 mL) was added DIPEA (77 mg, 0.60 mmol) and HATU (45 mg, 0.12 mmol), and the mixture was stirred at room temperature for 1 hour. The mixture was diluted with EtOAc, washed with water and brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to dryness. The residue was purified by prep-TLC (DCM: MeOH= 15: 1) to give the title compound (30 mg, yield 51.7%) as a yellow solid. LC / MS (ESI) (m / z): 587 (M+H)+. ALXN-0780-PCT01-NP Step 2: N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(6-(4-fluorophenyl)-4-oxo-5,6,7,8-tetrahydropyrido[3,2- d]pyrimidin-3(4H)-yl)-N-methylacetamide (Compound 64) To a solution of 2-(6-(4-fluorophenyl)-4-oxo-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)-N- methyl-N-((1-(phenylsulfonyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)methyl) acetamide (30 mg, 0.05 mmol) in MeOH (2 mL) was added NaOMe (0.15 mL, 0.15 mmol, 1.0 M in MeOH), and the mixture was stirred at room temperature for 3 hours. The mixture was filtered, and the filtrate was concentrated under reduced pressure to dryness. The residue was purified by prep-HPLC to give Compound 64 (5.1 mg, yield 22.4%) as a white solid.1H NMR (400 MHz, CD3OD) δ 8.74 (d, J = 14.2 Hz, 1H), 8.15 - 8.10 (m, 1H), 7.79 (d, J = 8.2 Hz, 1H), 7.45 - 7.36 (m, 3H), 7.08 (t, J = 8.8 Hz, 2H), 6.67 (d, J = 34.8 Hz, 1H), 5.11 - 4.89 (m, 3H), 4.81 (d, J = 4.7 Hz, 1H), 4.53 - 4.49 (m, 1H), 3.08 (d, J = 73.5 Hz, 3H), 2.87 - 2.79 (m, 1H), 2.61 - 2.51 (m, 1H), 2.20 - 2.12 (m, 1H), 2.07 - 1.99 (m, 1H). LC / MS (ESI) (m / z): 447 (M+H)+. RT (LC Method 1): 1.10 min. Compound 71 was prepared according to the procedure above, using 2-(6-(4-fluorophenyl)-5- methyl-4-oxo-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetic acid in place of 2-(6-(4-fluorophenyl)-4- oxo-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetic acid as the starting material (2.0 mg, yield 13.1%).1H NMR (400 MHz, CD3OD) δ 9.13 - 8.97 (m, 1H), 8.34 - 8.26 (m, 1H), 7.95 - 7.92 (m, 1H), 7.86 - 7.74 (m, 1H), 7.39 - 7.34 (m, 2H), 7.06 - 6.93 (m, 3H), 5.04 - 5.00 (m, 1H), 4.96 - 4.91 (m, 2H), 4.37 (d, J = 7.0 Hz, 1H), 4.20 - 4.14 (m, 1H), 3.25 (d, J = 5.4 Hz, 3H), 2.95 - 2.90 (m, 3H), 2.85 - 2.77 (m, 1H), 2.49 - 2.41 (m, 1H), 2.19 (d, J = 6.6 Hz, 1H), 2.10 - 2.03 (m, 1H). LC / MS (ESI) (m / z): 461 (M+H)+. RT (LC Method 1): 1.19 min. Scheme 32. Synthesis of Methyl 2-(5-methyl-4-oxo-6-(2-phenyloxazol-5-yl)-5,6,7,8- tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetate (Compound 65) mg, was mg, 3.77 mmol) and AcOH (1 mL), and the reaction mixture was degassed under N2atmosphere for three times and stirred at 70 °C for 10 minutes. NaBH3CN (356 mg, 5.67 mmol) was added to the reaction mixture in portions, and the resulting mixture was stirred at 70 °C for another 16 hours. The mixture was quenched with saturated aq. NH4Cl solution and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 5% MeOH in DCM) to give the title compound (450 mg, yield 71.9%) as a yellow solid. LC / MS (ESI) m / z: 332 (M+H)+. Step 2: 2-(6-(4-fluorophenyl)-5-methyl-4-oxo-5,6,7,8-tetrahydropyrido[3,2-d] pyrimidin-3(4H)-yl)acetic acid To a solution of methyl 2-(6-(4-fluorophenyl)-5-methyl-4-oxo-5,6,7,8-tetrahydropyrido [3,2-d]pyrimidin- 3(4H)-yl)acetate (450 mg, 1.36 mmol) in THF (4 mL) and water (1 mL) was added LiOH (98 mg, 4.10 mmol), and the reaction mixture was stirred at room temperature for 2 hours. The mixture was acidified with 1N aq. HCl to pH~3 and extracted with EtOAc twice. The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to dryness to give the title compound (400 mg, ALXN-0780-PCT01-NP yield 93.0%) as a yellow oil, which was used directly in the next reaction without further purification. LC / MS (ESI) m / z: 318 (M+H)+. Step 3: N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(6-(4-fluorophenyl)-5-methyl-4-oxo-5,6,7,8- tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetamide (Compound 65) To a mixture of 2-(6-(4-fluorophenyl)-5-methyl-4-oxo-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)- yl)acetic acid (30 mg, 0.09 mmol) and (1H-pyrrolo[3,2-c]pyridin-2-yl)methanamine hydrochloride (20 mg, 0.11 mmol) in DMF (1 mL) was added DIPEA (34.8 mg, 0.27 mmol) and HATU (41 mg, 0.11 mmol), and the reaction mixture was stirred at room temperature for 1 hour. The mixture was concentrated under reduced pressure to dryness. The residue was purified by prep-HPLC (C18, 20% - 98% MeCN in water with 0.1% FA) to give Compound 65 (8 mg, yield 19.9%) as a yellow solid.1H NMR (400 MHz, DMSO-d6) δ 11.82 (s, 1H), 8.92 - 8.87 (m, 2H), 8.20 (d, J = 6.0 Hz, 1H), 8.14 (s, 1H), 7.95 (s, 1H), 7.51 (d, J = 5.9 Hz, 1H), 7.36 - 7.32 (m, 2H), 7.17 - 7.12 (m, 2H), 6.60 (s, 1H), 4.67 - 4.60 (m, 2H), 4.54 - 4.51 (m, 2H), 4.13 - 4.09 (m, 1H), 2.80 (s, 3H), 2.74 - 2.67 (m, 1H), 2.34 - 2.27 (m, 1H), 2.09 - 2.02 (m, 1H), 2.00 - 1.91 (m, 1H). LC / MS (ESI) m / z: 447 (M+H)+. RT (LC Method 1): 1.11 min. Scheme 33. Synthesis of N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(4-oxo-6-phenyl-2-(pyridin-2-yl)- 5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl) acetamide (Compound 67) (1.50 g, 28.3 mmol) in DMF (5 mL) was added DIPEA (5.40 g, 41.8 mmol) and HBTU (8.00 g, 21.05 mmol), and the reaction mixture was stirred at room temperature for 2 hours. The mixture was diluted with EtOAc, washed with saturated aq. NH4Cl solution and brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 50% PE in EtOAc) to give the title compound (2.50 g, yield 83.3%) as a yellow solid. LC / MS (ESI) m / z: 216 (M+H)+. Step 2: 6-Bromo-3-(picolinamido)picolinamide To a mixture of 3-amino-6-bromopicolinamide (1.00 g, 4.65 mmol) and picolinic acid (0.70 g, 5.69 mmol) in MeCN (10 mL) was added TCFH (4.00 g, 14.2 mmol) and NMI (2.30 g, 28.0 mmol), and the reaction mixture was stirred at room temperature for 1 hour. The mixture was diluted with EtOAc, washed with saturated aq. NH4Cl solution and brine, dried over anhydrous Na2SO4, filtered, and concentrated under ALXN-0780-PCT01-NP reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 26% EtOAc in PE) to give the title compound (500 mg, yield 35.7%) as a white solid. LC / MS (ESI) m / z: 321 (M+H)+. Step 3: 6-bromo-2-(pyridin-2-yl)pyrido[3,2-d]pyrimidin-4(3H)-one A solution of 6-bromo-3-(picolinamido)picolinamide (500 mg, 1.56 mmol) in 2N aq. NaOH solution (6 mL, 12 mmol) was stirred at 70 °C for 3 hours. The mixture was concentrated under reduced pressure to give the title compound (300 mg, yield 63.8%) as a brown solid, which was used directly in the next reaction without further purification. LC / MS (ESI) m / z: 303 (M+H)+. Step 4: Methyl 2-(6-bromo-4-oxo-2-(pyridin-2-yl)pyrido[3,2-d]pyrimidin-3(4H)-yl)acetate To a mixture of 6-bromo-2-(pyridin-2-yl)pyrido[3,2-d]pyrimidin-4(3H)-one (300 mg, 0.99 mmol) and methyl 2-bromoacetate (190 mg, 1.24 mmol) in DMF (3 mL) was added Cs2CO3 (630 mg, 1.93 mmol) under N2 atmosphere, and the reaction mixture was degassed under N2 atmosphere for three times and stirred at 50 °C overnight. The mixture was diluted with EtOAc, washed with water and brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 33% EtOAc in PE) to give the title compound (260 mg, yield 69.3%) as a yellow solid. LC / MS (ESI) m / z: 376 (M+H)+. Step 5: Methyl 2-(4-oxo-6-phenyl-2-(pyridin-2-yl)pyrido[3,2-d]pyrimidin-3(4H)-yl)acetate To a mixture of methyl 2-(6-bromo-4-oxo-2-(pyridin-2-yl)pyrido[3,2-d]pyrimidin-3(4H)-yl)acetate (250 mg, 0.66 mmol) and phenylboronic acid (121 mg, 1.00 mmol) in 1,4-dioxane / water (7 mL, v / v = 6 / 1) was added K3PO4(424 mg, 2.00 mmol) and Pd(dtbpf)Cl2(43 mg, 0.06 mmol) under N2atmosphere, the reaction mixture was degassed under N2atmosphere for three times and stirred at 25 °C for 3 hours. The mixture was diluted with EtOAc, washed with water and brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 50% EtOAc in PE) to give the title compound (200 mg, yield 80.7%) as a yellow solid. LC / MS (ESI) m / z: 373 (M+H)+. Step 6: Methyl 2-(4-oxo-6-phenyl-2-(pyridin-2-yl)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetate To a solution of methyl 2-(4-oxo-6-phenyl-2-(pyridin-2-yl)pyrido[3,2-d]pyrimidin-3(4H)-yl)acetate (50 mg, 0.13 mmol) in AcOH (3 mL) was added NaBH3CN (100 mg, 1.59 mmol), and the reaction mixture was stirred at room temperature for 16 hours. The mixture was quenched with water and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 66% EtOAc in PE) to give the title compound (31 mg, yield 64.1%) as a yellow solid. LC / MS (ESI) m / z: 377 (M+H)+. Step 7: 2-(4-oxo-6-phenyl-2-(pyridin-2-yl)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetic acid To a solution of methyl 2-(4-oxo-6-phenyl-2-(pyridin-2-yl)-5,6,7,8-tetrahydropyrido [3,2-d]pyrimidin- 3(4H)-yl)acetate (30 mg, 0.07 mmol) in MeOH / water (2.0 mL, v / v = 4 / 1) was added LiOH (11 mg, 0.46 mmol), and the reaction mixture was stirred at room temperature for 2 hours. The mixture was acidified with 1N aq. HCl to pH~3 and extracted with EtOAc twice. The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to dryness to give the title compound (30 mg, ALXN-0780-PCT01-NP yield 99.2%) as a black solid, which was used directly in the next reaction without further purification. LC / MS (ESI) m / z: 363 (M+H)+. Step 8: N-((1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-2-(4-oxo-6-phenyl-2-(pyridin-2-yl)-5,6,7,8- tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetamide (Compound 67) To a mixture of 2-(4-oxo-6-phenyl-2-(pyridin-2-yl)-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)- yl)acetic acid (30 mg, 0.08 mmol) and (1H-pyrrolo[3,2-c]pyridin-2-yl)methanamine hydrochloride (24 mg, 0.16 mmol) in DMF (3 mL) was added DIPEA (32 mg, 0.24 mmol) and HATU (37 mg, 0.09 mmol), and the mixture was stirred at room temperature for 1 hour. The mixture was diluted with EtOAc, washed with water and brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to dryness. The residue was purified by prep-TLC (DCM: MeOH= 5: 1) and further purified by prep-HPLC (C18, 30% - 98% MeCN in water with 0.1% NH3.H2O) to give Compound 67 (2 mg, yield 5%) as a white solid.1H NMR (400 MHz, CD3OD) δ 8.81 (s, 1H), 8.49 - 8.45 (m, 1H), 8.17 (d, J = 6.1 Hz, 1H), 7.84 (d, J = 3.6 Hz, 2H), 7.57 - 7.54 (m, 1H), 7.39 - 7.34 (m, 5H), 7.30 - 7.26 (m, 1H), 6.61 (s, 1H), 5.11 (s, 2H), 4.60 - 4.57 (m, 1H), 4.55 (s, 2H), 2.89 - 2.81 (m, 1H), 2.66 - 2.55 (m, 1H), 2.24 - 2.18 (m, 1H), 2.12 - 2.02 (m, 1H). LC / MS (ESI) (m / z): 492 (M+H)+. RT (LC Method 1): 1.24 min. Scheme 34. Synthesis of 2-(6-(4-fluorophenyl)-4-oxo-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)- yl)-N-methyl-N-((1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)methyl) acetamide (Compound 69) (4.5 g, 1.38 was g, room atmosphere, and the reaction mixture was stirred at room temperature for 1 hour. The mixture was diluted with water and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 10% MeOH in DCM) to give the title compound (500 mg, yield 45.7%) as a yellow solid. LC / MS (ESI) m / z: 161 (M+H)+. Step 2: (Z)-N-methyl-1-(1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)methanimine To a solution of 1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carbaldehyde (500 mg, 3.12 mmol) in MeNH2 / MeOH solution (5 mL, 5% w.t.) was added MgSO4 (20 mg, 0.17 mmol), AcOH (0.5 mL) and NaBH3CN (290 mg, 4.68 mmol). The reaction mixture was stirred at 60 °C for 4 hours. The mixture was quenched with ice water and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 10% MeOH in DCM) to give the title compound (500 mg, yield 92.5%) as a yellow solid. LC / MS (ESI) m / z: 174 (M+H)+. ALXN-0780-PCT01-NP Step 3: N-methyl-1-(1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)methanamine To a solution of (Z)-N-methyl-1-(1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)methanimine (500 mg, 0.096 mmol) in MeOH (5 mL) was added NaBH4 (600 mg, 15.8 mmol), and the reaction mixture was stirred at room temperature for 4 hours. The mixture was quenched with saturated aq. NH4Cl solution and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 10% MeOH in DCM) to give the title compound (400 mg, yield 79.2%) as a yellow solid. LC / MS (ESI) m / z: 176 (M+H)+. Step 4: 2-(6-(4-Fluorophenyl)-2-(furan-2-yl)-4-oxo-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetic acid To a solution of tert-butyl methyl((1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)methyl) carbamate (400 mg, 2.29 mmol) in THF (5.0 mL) was added (Boc)2O (500 mg, 2.29 mmol) and TEA (0.3 mL), and the reaction mixture was stirred at room temperature for 2 hours. The mixture was concentrated under reduced pressure to dryness. The residue was purified by flash chromatography (silica gel, 0 - 10% MeOH in DCM) to give the title compound (176 mg, yield 28.0%) as a yellow solid. LC / MS (ESI) m / z: 276 (M+H)+. Step 5: N-methyl-1-(1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)methanamine To a solution of N-methyl-1-(1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)methanamine (176 mg, 0.64 mmol) in DCM (1.5 mL) was added HCl / 1,4-dioxane (1.0 mL), and the reaction mixture was stirred at room temperature for 1 hour. The mixture concentrated under reduced pressure to dryness to give the title compound (108 mg, yield 97.2%) as a yellow solid, which was used directly in the next reaction without further purification. LC / MS (ESI) m / z: 176 (M+H)+. Step 6: 2-(6-(4-Fluorophenyl)-4-oxo-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)-N-methyl-N-((1-methyl- 1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)acetamide (Compound 69) To a mixture of N-methyl-1-(1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)methanamine (30 mg, 0.17 mmol) and 2-(6-(4-fluorophenyl)-4-oxo-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-3(4H)-yl)acetic acid (40 mg, 0.13 mmol) in DMF (1 mL) was added DIPEA (85 mg, 0.65 mmol) and HATU (75 mg, 0.20 mmol), and the reaction mixture was stirred at room temperature for 1 hour. The mixture was concentrated under reduced pressure to dryness. The residue was purified by prep-HPLC (C18, 10 - 95% MeCN in water with 0.1% FA) to give Compound 69 (4.2 mg, yield 7.0%) as a white solid.1H NMR (400 MHz, CD3OD) δ 8.89 (s, 1H), 8.27 (d, J = 6.4 Hz, 1H), 7.80 - 7.70 (m, 2H), 7.43 - 7.37 (m, 2H), 7.09 (t, J = 8.8 Hz, 2H), 6.93 - 6.82 (m, 1H), 5.06 - 4.94 (m, 4H), 4.53 - 4.42 (m, 1H), 3.88 (s, 3H), 3.19 (s, 3H), 2.92 - 2.79 (m, 1H), 2.65 - 2.56 (m, 1H), 2.21 - 2.03 (m, 2H). LC / MS (ESI) m / z: 461 (M+H)+. RT (LC Method 1): 1.12 min. Scheme 35. Synthesis of 2-(6-(4-fluorophenyl)-5-methyl-4-oxo-5,6,7,8-tetrahydropyrido[3,2- d]pyrimidin-3(4H)-yl)-N-((1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)acetamide (Compound 70) To a d]pyrimidin-3(4H)- yl)acetic acid (30 mg, 0.13 mmol) and (1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)methanamine (16 mg, 0.13 ALXN-0780-PCT01-NP mmol) in DMF (1.5 mL) was added DIPEA (36 mg, 0.39 mmol) and HATU (43 mg, 0.16 mmol), and the reaction mixture was stirred at room temperature for 1 hour. The mixture was diluted with EtOAc, washed with water and brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to dryness. The residue was purified by prep-HPLC (C18, 30 - 95% MeCN in water with 0.1% NH3.H2O) to give Compound 70 (8 mg, yield 13.4%) as a white solid.1H NMR (400 MHz, CD3OD) δ 8.71 - 8.69 (m, 1H), 8.16 (d, J = 6.0 Hz, 1H), 7.95 (s, 1H), 7.44 (d, J = 6.0 Hz, 1H), 7.37 - 7.33 (m, 2H), 7.04 - 6.99 (m, 2H), 6.69 (s, 1H), 4.70 - 4.67 (m, 4H), 4.14 (dd, J = 8.1, 3.7 Hz, 1H), 3.80 (s, 3H), 2.86 (s, 3H), 2.82 - 2.73 (m, 1H), 2.46 - 2.38 (m, 1H), 2.20 - 2.13 (m, 1H), 2.09 - 2.00 (m, 1H). LC / MS (ESI) m / z: 461 (M+H)+. RT (LC Method 1): 1.13 min. The following compounds were prepared based on Scheme 35. # Reactant A Reactant B Characterization Data 1H NMR (400 MHz, CD3OD) δ 8.90 (s, 1H), 8.44 (s, 1H), 8.26 (d, J = 6.2 Hz, 1H), 7.93 (s, 1H), 7.74 (d, J = 6.3 Hz, 1H), 7.36 (dd, J = 8.5, 5.4 Hz, N 2H), 7.03 (t, J = 8.7 Hz, 2H), 6.91 (s, 1H), 5.06 - 4.94 (m, 4H), 4.18 - 72 H 4.14 (m, 1H), 3.93 - 3.83 (m, 3H), 3.20 - 3.09 (m, 3H), 2.90 - 2.87 (m, N Cl NH3H), 2.84 - 2.76 (m, 1H), 2.48- 2.40 (m, 1H), 2.20 - 2.15 (m, 1H), 2.08 - 2.01 (m, 1H). LC / MS (ESI) m / z: 475 (M+H)+. RT (LC Method 1): 1.17 min. 1H NMR (400 MHz, CD3OD) δ 8.70 (s, 1H), 8.15 (d, J = 5.9 Hz, 1H), 7.80 (s, 1H), 7.43 (d, J = 5.9 Hz, 1H), 7.38 - 7.34 (m, 2H), 7.08 - 7.03 120 (m, 2H), 6.66 (s, 1H), 4.71 (s, 2H), 4.67 (s, 2H), 4.49 - 4.45 (m, 1H), 3.78 (s, 3H), 2.86 - 2.77 (m, 1H), 2.60 - 2.53 (m, 1H), 2.17 - 2.11 (m, 1H), 2.04 - 1.99 (m, 1H). LC / MS (ESI) m / z: 447 (M+H)+. RT (LC Method 1): 0.76 min. 1H NMR (400 MHz, DMSO-d6) δ 8.96 (t, J = 5.9 Hz, 1H), 8.90 (d, J = 3.3 Hz, 1H), 7.79 (s, 1H), 7.66 (s, 1H), 7.56 (d, J = 12.9 Hz, 1H), 7.35 - 121 7.28 (m, 2H), 7.15 (t, J = 8.9 Hz, 2H), 6.78 (s, 2H), 5.52 (d, J = 2.1 Hz, 1H), 4.68 (d, J = 2.6 Hz, 2H), 4.52 (d, J = 5.9 Hz, 2H), 4.49 - 4.45 (m, 1H), 2.71 - 2.61 (m, 1H), 2.40 - 2.32 (m, 1H), 2.05 - 1.90 (m, 2H). LC / MS (ESI) m / z: 478 (M+H)+. RT (LC Method 1): 0.98 min. 1H NMR (400 MHz, DMSO-d6) δ 9.07 - 9.03 (m, 2H), 8.37 (d, J = 5.5 Hz, 1H), 7.99 (d, J = 5.5 Hz, 1H), 7.77 (s, 1H), 7.54 - 7.50 (m, 3H), 7.47 122 (s, 1H), 7.42 - 7.37 (m, 3H), 7.33 - 7.27 (m, 2H), 5.55 (d, J = 2.1 Hz, 1H), 4.67 - 4.60 (m, 4H), 4.54 - 4.50 (m, 1H), 2.72 - 2.66 (m, 1H), 2.43 - 2.33 (m, 1H), 2.09 - 1.97 (m, 2H). LC / MS (ESI) m / z: 526 (M+H)+. RT (LC Method 1): 1.70 min. 1H NMR (400 MHz, CD3OD) δ 8.70 (d, J = 0.8 Hz, 1H), 8.15 (d, J = 6.0 Hz, 1H), 7.81 (s, 1H), 7.54 - 7.50 (m, 2H), 7.48 - 7.42 (m, 4H), 7.37 - 123 7.32 (m, 1H), 7.26 - 7.22 (m, 1H), 7.20 - 7.14 (m, 1H), 6.68 (s, 1H), 4.72 (s, 2H), 4.68 (s, 2H), 4.57 - 4.53 (m, 1H), 3.79 (s, 3H), 2.87 - 2.79 (m, 1H), 2.63 - 2.55 (m, 1H), 2.24 - 2.17 (m, 1H), 2.13 - 2.03 (m, 1H). LC / MS (ESI) m / z: 523 (M+H)+. RT (LC Method 1): 1.67 min. 1H NMR (400 MHz, CD3OD) δ 8.95 (s, 1H), 8.31 (d, J = 5.7 Hz, 1H), 7.91 (d, J = 5.7 Hz, 1H), 7.81 (s, 1H), 7.47 (s, 1H), 7.33 (s, 4H), 4.74 (d, 124 J = 5.2 Hz, 4H), 4.48 (dd, J = 8.0, 3.5 Hz, 1H), 2.80 (ddd, J = 17.9, 8.6, 5.8 Hz, 1H), 2.54 (dt, J = 17.7, 5.6 Hz, 1H), 2.22 – 1.93 (m, 2H). LC / MS (ESI) m / z: 466 (M+H)+. RT (LC Method 1): 1.25 min. 1H NMR (400 MHz, DMSO) δ 9.12 (s, 1H), 9.04 (s, 1H), 8.38 (d, J = 5.5 Hz, 1H), 8.00 (d, J = 5.6 Hz, 1H), 7.41 (d, J = 7.5 Hz, 1H), 7.31 (dd, J = 126a8.4, 5.5 Hz, 2H), 7.23 – 7.12 (m, 3H), 7.07 (d, J = 3.9 Hz, 1H), 5.94 (s, 1H), 4.92 – 4.77 (m, 4H), 4.63 (d, J = 5.5 Hz, 2H), 4.55 (s, 1H), 2.63 (t, J = 5.8 Hz, 1H) and 2.00-1.85 (m, 6H). LC / MS (ESI) m / z: 578 (M+H)+. RT (LC Method 1): 1.84 min. 1H NMR (400 MHz, CD3OD) δ 8.82 (s, 1H), 8.47 – 8.33 (m, 1H), 7.80 (s, 1H), 7.58 (d, J = 5.8 Hz, 1H), 7.33 (s, 4H), 6.92 (s, 1H), 4.74 (s, 2H), 129 4.63 (s, 2H), 4.48 (dd, J = 7.9, 3.5 Hz, 1H), 2.90 – 2.72 (m, 1H), 2.54 (dt, J = 17.8, 5.6 Hz, 1H), 2.23 – 1.95 (m, 2H). LC / MS (ESI) m / z: 450 (M+H)+. RT (LC Method 1): 1.20 min. ALXN-0780-PCT01-NP # Reactant A Reactant B Characterization Data 1H NMR (400 MHz, MeOD-d4) δ 8.96 (1H, s), 8.31 (1H, d, J = 5.6 Hz), 7.92 (1H, d, J = 5.6 Hz), 7.75 (1H, s), 7.47 (1H, s), 7.32 (2H, m), 6.9833 (2H, m), 4.74 (4H, m), 2.55 (1H, dt, J = 17.5, 3.5 Hz), 2.36 (1H, m), 2.18 (1H, m), 1.90 (1H, m) and 1.57 (3H, s). LC / MS (ESI) m / z: 464 (M+H)+. RT (LC Method 1): 1.16 min. 1H NMR (400 MHz, DMSO) δ 9.11 (s, 1H), 9.04 (s, 1H), 8.38 (d, J = 5.5 Hz, 1H), 8.00 (d, J = 5.6 Hz, 1H), 7.41 (d, J = 7.5 Hz, 1H), 7.31 (dd, J =4a8.4, 5.5 Hz, 2H), 7.23 – 7.12 (m, 3H), 7.07 (d, J = 3.9 Hz, 1H), 5.94 (s, 2H), 4.93 – 4.77 (m, 2H), 4.63 (d, J = 5.5 Hz, 2H), 4.55 (s, 1H), 2.64 (t, J = 5.8 Hz, 1H) and 1.99-1.85 (m, 2H). LC / MS (ESI) m / z: 550 (M+H)+. RT (LC Method 1): 1.86 min. 1H NMR (400 MHz, MeOD-d4) δ 8.96 (1H, s), 8.31 (1H, d, J = 5.7 Hz), 7.92 (1H, d, J = 5.6 Hz), 7.75 (1H, s), 7.48 (1H, s), 7.33 (2H, m), 6.9937 (2H, m), 4.74 (4H, m), 2.55 (1H, m), 2.37 (1H, m), 2.18 (1H, m), 1.90 (1H, m) and 1.57 (3H, s). LC / MS (ESI) m / z: 464 (M+H)+. RT (LC Method 1): 1.07 min. 1H NMR (400 MHz, CD3OD) δ 8.70 (s, 1H), 8.09 (d, J = 5.9 Hz, 1H), 7.39 - 7.32 (m, 3H), 7.09 - 7.03 (m, 2H), 6.56 (s, 1H), 4.92 - 4.90 (m,43 2H), 4.63 - 4.60 (m, 3H), 2.85 - 2.77 (m, 1H), 2.61 - 2.53 (m, 1H), 2.19 - 2.12 (m, 1H), 2.10 - 2.02 (m, 1H). LC / MS (ESI) m / z: 501 (M+H)+. RT (LC Method 1): 1.43 min. 1H NMR (400 MHz, CD3OD) δ 8.89 (s, 1H), 8.25 (d, J = 5.7 Hz, 1H),50 7.85(d, J = 5.7 Hz, 1H), 7.78 (s, 1H), 7.41 - 7.37 (m, 3H), 7.04 (t, J = 8.8 Hz, 2H), 4.69 (s, 2H), 4.66 (s, 2H), 4.42 - 4.34 (m, 2H), 4.09 - 4.04 (m, 1H). LC / MS (ESI) m / z: 452 (M+H)+. RT (LC Method 1): 0.86 min. 1H NMR (400 MHz, DMSO) δ 8.99 (d, J = 5.2 Hz, 1H), 8.40 – 8.18 (m, 2H), 7.95 (t, J = 5.6 Hz, 1H), 7.43 – 7.21 (m, 2H), 7.08 (t, J = 8.7 Hz,1a1H), 4.64 – 4.47 (m, 2H), 4.04 (s, 17H), 1.90 (qd, J = 13.4, 6.7 Hz, 1H), 1.62 – 1.34 (m, 4H) and 0.92 – 0.82 (m, 3H). LC / MS (ESI) m / z: 450(M+H)+. RT (LC Method 1): 1.02 min. 1H NMR (400 MHz, CD3OD) δ 9.00 (s, 1H), 8.33 (d, J = 5.6 Hz, 1H), 7.98 (d, J = 5.7 Hz, 1H), 7.77 (s, 1H), 7.49 (s, 1H), 7.25 - 7.21 (m, 2H),52 6.98 (t, J = 8.4 Hz, 2H), 4.73 (s, 2H), 4.72 (s, 2H), 3.29 - 3.25 (m, 1H), 2.77 - 2.69 (m, 4H), 2.08 - 2.03 (m, 1H), 1.90 - 1.80 (m, 2H), 1.76 - 1.68 (m, 1H). LC / MS (ESI) (m / z): 478 (M+H)+. RT (LC Method 1): 1.34 min. 1H NMR (400 MHz, CD3OD) δ 8.99 (s, 1H), 8.95 (s, 1H), 8.32 (d, J = 5.6 Hz, 1H), 8.04 (s, 1H), 7.92 (d, J = 5.3 Hz, 1H), 7.42 - 7.37 (m, 3H), 7.0859 (t, J = 8.1 Hz, 2H), 5.17 (s, 2H), 4.64 (s, 2H), 4.58 - 4.54 (m, 1H), 2.90 - 2.81 (m, 1H), 2.66 - 2.56 (m, 1H), 2.21 - 2.18 (m, 1H), 2.06 - 2.03 (m, 1H). LC / MS (ESI) m / z: 533 (M+H)+. RT (LC Method 1): 1.24 min. 1H NMR (400 MHz, DMSO-d6) δ 9.11 - 9.07 (m, 1H), 9.00 (s, 1H), 7.80 (s, 1H), 7.58 (s, 1H), 7.43 - 7.40 (m, 2H), 7.22 - 7.17 (m, 2H), 6.79 (s,60 2H), 5.45 (s, 1H), 4.65 - 4.61 (m, 4H), 4.46 - 4.43 (m, 1H), 4.33 - 4.29 (m, 1H), 4.11 - 4.07 (m, 1H). LC / MS (ESI) (m / z): 468 (M+H)+. RT (LC Method 1): 0.83 min. 1H NMR (400 MHz, CD3OD) δ 8.99 (d, J = 2.0 Hz, 1H), 8.71 (s, 1H), 8.17 (d, J = 5.9 Hz, 1H), 8.04 (d, J = 2.1 Hz, 1H), 7.45 - 7.43 (m, 1H),64 7.41 - 7.38 (m, 2H), 7.10 - 7.06 (m, 2H), 6.59 (s, 1H), 5.35 - 5.34 (m, 1H), 5.13 (s, 2H), 4.60 (s, 2H), 3.74 (s, 3H), 2.88 - 2.82 (m, 1H), 2.64 - 2.58 (m, 1H), 2.20 - 2.18 (m, 2H). LC / MS (ESI) (m / z): 530 (M+H)+. RT (LC Method 1): 1.23 min. 1H NMR (400 MHz, DMSO-d6) δ 9.11 - 9.08 (m, 1H), 9.01 (s, 1H), 7.815a(s, 1H), 7.59 (s, 1H), 7.45 - 7.40 (m, 4H), 6.80 (s, 2H), 5.54 (s, 1H), 4.65 - 4.61 (m, 4H), 4.48 - 4.45 (m, 1H), 4.34 - 4.30 (m, 1H), 4.14 - 4.09 (m, 1H). LC / MS (ESI) (m / z): 484 (M+H)+. RT (LC Method 1): 1.08 min. 1H NMR (400 MHz, DMSO-d6) δ 9.09 (t, J = 5.9 Hz, 1H), 8.86 (s, 1H),67 7.80 (s, 1H), 7.43 - 7.38 (m, 5H), 6.76 (s, 2H), 5.54 (s, 1H), 4.67 - 4.62 (m, 4H), 4.47 - 4.44 (m, 1H), 4.33 - 4.28 (m, 1H), 4.13 - 4.07 (m, 1H). LC / MS (ESI) (m / z): 484 (M+H)+. RT (LC Method 1): 1.05 min. 1H NMR (400 MHz, DMSO-d6) δ 9.07 - 9.02 (m, 2H), 8.37 (d, J = 5.5 Hz, 1H), 7.99 (d, J = 5.5 Hz, 1H), 7.81 (s, 1H), 7.46 (s, 1H), 7.43 - 7.3873 (m, 4H), 5.54 (s, 1H), 4.66 - 4.60 (m, 4H), 4.47 - 4.43 (m, 1H), 4.33 - 4.28 (m, 1H), 4.13 - 4.07 (m, 1H). LC / MS (ESI) (m / z): 468 (M+H)+. RT (LC Method 1): 1.06 min. 1H NMR (400 MHz, CD3OD) δ 8.81 (s, 1H), 7.84 (s, 1H), 7.48 - 7.44 (m,74 3H), 7.13 - 7.08 (m, 2H), 4.77 (s, 2H), 4.75 (s, 2H), 4.48 - 4.41 (m, 2H), 4.15 - 4.10 (m, 1H). LC / MS (ESI) (m / z): 468 (M+H)+. RT (LC Method 1): 0.74 min. ALXN-0780-PCT01-NP # Reactant A Reactant B Characterization Data 1H NMR (400 MHz, CD3OD) δ 8.18 (s, 1H), 7.81 (s, 1H), 7.54 (s, 1H),6a7.33 (s, 4H), 4.80 (s, 2H), 4.75 (s, 2H), 4.50 - 4.47 (m, 1H), 2.84 - 2.77 (m, 1H), 2.59 - 2.52 (m, 1H), 2.17 - 2.12 (m, 1H), 2.05 - 1.99 (m, 1H). LC / MS (ESI) m / z: 482 (M+H)+. RT (LC Method 1): 1.19 min. 1H NMR (400 MHz, DMSO) δ 9.04 – 8.93 (m, 2H), 8.30 (d, J = 5.5 Hz, 1H), 7.88 (d, J = 5.5 Hz, 1H), 7.38 (s, 1H), 7.25 (dd, J = 8.5, 5.5 Hz, 2H), 7.08 (t, J = 8.8 Hz, 2H), 5.15 (d, J = 2.5 Hz, 1H), 4.78 – 4.63 (m,1a2H), 4.55 (d, J = 5.9 Hz, 2H), 4.36 (dt, J = 6.5, 3.1 Hz, 1H), 2.57 (dt, J = 17.7, 6.4 Hz, 1H), 2.41 (d, J = 17.5 Hz, 2H), 2.26 (dt, J = 17.5, 6.0 Hz, 1H), 1.98 – 1.81 (m, 2H), 1.48 – 1.39 (m, 2H) and 0.74 (s, 9H). LC / MS (ESI) m / z: 421 (M+H)+. RT (LC Method 1): 1.91 min. 1H NMR (400 MHz, DMSO) δ 8.93 (t, J = 5.9 Hz, 1H), 8.78 (s, 1H), 8.45 (s, 1H), 8.28 (d, J = 5.8 Hz, 1H), 7.96 (s, 1H), 7.58 (d, J = 5.8 Hz, 1H),2a7.25 (dd, J = 8.6, 5.6 Hz, 2H), 7.08 (t, J = 8.7 Hz, 2H), 6.68 (d, J = 14.5 Hz, 2H), 5.15 (s, 1H), 4.79 – 4.64 (m, 3H), 4.58 (d, J = 5.8 Hz, 2H), 4.36 (s, 1H), 1.91-188 (m, 2H), 1.48 – 1.39 (m, 2H) and 0.76 (s, 9H). LC / MS (ESI) m / z: 534 (M+H)+. RT (LC Method 1): 1.97 min. 1H NMR (400 MHz, DMSO-d6) δ 9.10 - 9.04 (m, 1H), 8.99 (s, 1H), 7.74 (s, 1H), 7.58 (s, 1H), 7.41 - 7.35 (m, 2H), 7.32 - 7.26 (m, 2H), 6.79 (s,9a2H), 5.55 (s, 1H), 4.62 (t, J = 5.4 Hz, 4H), 4.49 - 4.44 (m, 1H), 2.69 - 2.64 (m, 1H), 2.36 - 2.30 (m, 1H), 2.02 - 1.91 (m, 2H). LC / MS (ESI) (m / z): 482 (M+H)+. RT (LC Method 1): 1.12 min. 1H NMR (400 MHz, CDCl3) δ 8.33 (s, 1H), 8.27 (s, 1H), 7.90 (d, J = 9.1 Hz, 1H), 7.31 (dd, J = 8.4, 5.4 Hz, 2H), 7.13 (t, J = 5.8 Hz, 1H), 7.04 (t,8aJ = 8.5 Hz, 2H), 6.91 (s, 1H), 6.81 (s, 1H), 4.72 (s, 1H), 4.60 (q, J = 8.0 Hz, 5H), 4.44 – 4.37 (m, 1H), 2.88 (ddd, J = 16.6, 9.9, 6.0 Hz, 1H), 2.75 – 2.64 (m, 1H), 2.31 (s, 3H), 2.15 (s, 1H) and 2.03 (tt, J = 9.6, 5.4 Hz, 1H). LC / MS (ESI) m / z: 574 (M+H)+. RT (LC Method 1): 1.46 min. 1H NMR (400 MHz, CDCl3) δ 9.00 (s, 1H), 8.43 (s, 1H), 7.72 (d, J = 5.5 Hz, 1H), 7.46 (s, 1H), 7.34 (dd, J = 8.7, 5.6 Hz, 1H), 7.25 (s, 1H), 7.06 a (t, J = 8.5 Hz, 1H), 6.55 (s, 1H), 6.28 (d, J = 10.6 Hz, 1H), 4.78 (s, 1H),0 4.72 (q, J = 5.7 Hz, 2H), 4.44 (d, J = 9.0 Hz, 1H), 3.85 (d, J = 4.6 Hz, 3H), 3.72 (s, 3H), 2.95 – 2.84 (m, 1H), 2.69 (s, 3H) and 2.35 – 2.26 (m, + 4H). LC / MS (ESI) m / z: 544 (M+H) . RT (LC Method 1): 1.36 min. 1H NMR (400 MHz, DMSO-d6) δ 8.85 - 8.81 (m, 1H), 8.39 (s, 1H), 7.36 - 7.32 (m, 2H), 7.18 - 7.13 (m, 2H), 7.10 (s, 1H), 6.82 (s, 1H), 5.82 (s,02 2H), 4.99 (s, 1H), 4.63 (d, J = 2.7 Hz, 2H), 4.46 (d, J = 5.5 Hz, 2H), 4.40 - 4.36 (m, 1H), 2.85 - 2.81 (m, 4H), 2.67 - 2.61 (m, 1H), 2.36 - 2.30 (m, 1H), 2.03 - 1.90 (m, 2H), 1.54 - 1.49 (m, 4H), 1.48 - 1.43 (m, 2H). LC / MS (ESI) (m / z): 548 (M+H)+. RT (LC Method 1): 1.78 min. 1H NMR (400 MHz, DMSO-d6) δ 8.90 (1H, t, J = 5.8 Hz), 8.39 (1H, s), 7.79 (1H, s), 7.39 (2H, d, J = 8.4 Hz), 7.25 (2H, d, J = 8.5 Hz), 7.10 (1H,03 s), 6.82 (1H, s), 5.83 (2H, br s), 5.71 (1H, s), 4.62 (2H, m), 4.46 (4H, m) and 1.01 (3H, d, J = 6.3 Hz). LC / MS (ESI) m / z: 497 (M+H)+. RT (LC Method 1): 1.32 min. 1H NMR (400 MHz, CD3OD) δ 8.52 (s, 1H), 8.37 (s, 1H), 7.94 (d, J = 8.1 Hz, 2H), 7.86 (d, J = 3.3 Hz, 1H), 7.82 (s, 1H), 7.60 (d, J = 3.3 Hz, 1H),04 7.49 (d, J = 8.1 Hz, 2H), 7.16 (s, 1H), 6.96 (s, 1H), 4.74 (s, 2H), 4.60 (d, J = 4.9 Hz, 4H), 2.89 – 2.75 (m, 1H), 2.57 (dt, J = 17.7, 5.8 Hz, 1H), 2.27 – 2.00 (m, 2H). LC / MS (ESI) m / z: 530 (M+H)+. 1H NMR (400 MHz, CDCl3) d 8.43 (s, 1H), 7.84 (s, 1H), 7.70 (d, J = 5.4 Hz, 1H), 7.32 (dd, J = 8.5, 5.3 Hz, 2H), 7.26 (s, 3H), 7.20 – 7.12 (m,5a1H), 7.05 (t, J = 8.5 Hz, 2H), 4.72 – 4.63 (m, 3H), 4.57 (s, 2H), 4.38 (d, J = 9.3 Hz, 1H), 3.93 (s, 3H), 2.89 (ddd, J = 17.0, 10.3, 6.1 Hz, 1H), 2.70 (dt, J = 17.9, 4.7 Hz, 1H) and 2.02 (dtd, J = 15.0, 9.9, 5.4 Hz, 1H). LC / MS (ESI) m / z: 613 (M+H)+. RT (LC Method 1): 1.62 min. 1H NMR (400 MHz, CD3OD) δ 8.98 (d, J = 1.5 Hz, 1H), 8.35 (s, 1H), 8.02 (d, J = 1.8 Hz, 1H), 7.36 (d, J = 3.1 Hz, 4H), 7.06 (s, 1H), 6.96 (s,12 1H), 5.15 (s, 2H), 4.62 - 4.61 (m, 1H), 4.49 (s, 2H), 2.89 - 2.79 (m, 2H), 2.66 - 2.54 (m, 2H). LC / MS (ESI) (m / z): 564 (M+H)+. RT (LC Method 1): 1.40 min. 1H NMR (400 MHz, CD3OD) δ 8.88 (s, 1H), 7.82 (s, 1H), 7.77 (s, 1H), 7.42 (d, J = 8.5 Hz, 2H), 7.35 (d, J = 8.5 Hz, 2H), 4.78 (s, 2H), 4.74 (s,3a2H), 4.45 - 4.41 (m, 1H), 3.11 - 3.03 (m, 1H), 2.26 - 2.21 (m, 1H), 1.69 - 1.64 (m, 1H), 1.31 (d, J = 6.9 Hz, 3H). LC / MS (ESI) (m / z): 496 (M+H)+. RT (LC Method 1): 1.44 min. ALXN-0780-PCT01-NP # Reactant A Reactant B Characterization Data 1H NMR (400 MHz, DMSO-d6) δ 9.12 - 9.04 (m, 1H), 8.99 (s, 1H), 7.79 214a(s, 1H), 7.58 (s, 1H), 7.29 (d, J = 8.7 Hz, 2H), 6.92 (d, J = 8.7 Hz, 2H), 6.78 (s, 2H), 5.24 (s, 1H), 4.68 - 4.52 (m, 4H), 4.41 - 4.25 (m, 2H), 4.08 - 3.97 (m, 1H), 3.74 (s, 3H). LC / MS (ESI) (m / z): 480 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ 9.06 (d, J = 5.6 Hz, 1H), 9.03 (d, J = 2.4 Hz, 1H), 7.73 (s, 1H), 7.38 (d, J = 8.4 Hz, 2H), 7.29 (d, J = 8.5 Hz, 216a2H), 6.64 (s, 2H), 5.55 (d, J = 2.2 Hz, 1H), 4.60 (d, J = 5.2 Hz, 2H), 4.55 (d, J = 5.2 Hz, 2H), 4.48 - 4.45 (m, 1H), 2.67-2.62 (m, 1H), 2.36 - 2.30 (m, 1H), 2.01 - 1.95 (m...

Claims

1. ALXN-0780-PCT01-NP Claims 1. A compound of Formula (I): , or a pharmaceutically acceptable wherein ; Rais independently selected from absent, H, C1-C6 X2is N or CRb, wherein Rbis absent or H; each of X3, X4, and X5is independently selected from NRcand C(Rc)2, wherein each Rcis independently selected from absent, H, halo, NH2, NH(C1-C6alkyl), N(C1-C6alkyl)2, or C1-C6alkyl, and only one of X3and X5can be NRcwhen X4is NRc; R6is H or halo; and R7is H, halo, NH2, NH(C1-C6 alkyl), N(C1-C6 alkyl)2, C1-C6 alkyl, or C3-C6 cycloalkyl; and each is independently selected from a single bond and a double bond; each of R1, R1’, R2, and R2’ is independently selected from H, halo, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, and (C1-C6 alkoxy)(C1-C6 alkyl); R3is H; halo; C(O)Rd, wherein Rdis OH, O(C1-C6 alkyl), NH2, NH(C1-C6 alkyl), or N(C1-C6 alkyl)2; OC(O)N(Re)2, wherein each Reis independently selected from H and C1-C6alkyl; NRfC(O)N(Rf)2, wherein each Rfis independently selected from H and C1-C6alkyl; C1-C6alkyl; C1-C6haloalkyl; (C1-C6alkoxy)(C1-C6alkyl); C6-C14 aryl; C3-C8 carbocyclyl; 5- to 10-membered heteroaryl containing 1, 2, or 3 ring atoms independently selected from N, O, and S; 4- to 10-membered heterocyclyl containing 1, 2, or 3 ring atoms independently selected from N, O, and S; 6-membered heterocycloalkenyl containing 1, 2, or 3 ring atoms independently selected from N, O, and S; (4- to 10-membered heterocyclyl)oxy containing 1, 2, or 3 ring atoms independently selected from N, O, and S, or (5- to 9-membered heteroaryl)oxy containing 1, 2, or 3 ring atoms independently selected from N, O, and S; wherein R3is optionally substituted with one or more substituents independently selected from halo; C1-C6alkyl; C1-C6haloalkyl; (C1-C6alkoxy)(C1-C6alkyl); and 5- or 6-membered heterocycloalkyl containing 1, 2, or 3 ring atoms independently selected from N, O, and S; each of R4and R4’is independently selected from H, halo, C1-C6 alkyl, C1-C6haloalkyl, C1- C6hydroxyalkyl, and (C1-C6alkoxy)(C1-C6alkyl); R5is H or C1-C6alkyl; ALXN-0780-PCT01-NP R8is halo; R9is 5- to 10-membered heteroaryl containing 1, 2, 3, or 4 ring atoms independently selected from N, O, and S; X is C(Rg)2, O, or S; each Rgis independently selected from H, halo, OH, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and (C1-C6alkoxy)(C1-C6alkyl); or both Rg, together with the carbon atom to which they are attached, form C3-C8spirocyclic cycloalkyl or 4- to 6-membered spirocyclic heterocycloalkyl containing 1 or 2 oxygen atoms; L is a bond or C1-C6 alkylene optionally substituted with one or more substituents independently selected from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, (C1-C6 alkoxy)(C1-C6 alkyl), and oxo; and B is C1-C6alkyl; C6-C14aryl; C3-C14carbocyclyl; 5- to 14-membered heterocyclyl containing 1, 2, or 3 ring atoms independently selected from N, O, and S; and 5- to 10-membered heteroaryl containing 1, 2, or 3 ring atoms independently selected from N, O, and S; wherein B is optionally substituted with one or more substituents independently selected from halo; cyano; COORh, wherein Rhis H or C1-C6 alkyl; S(O)2(C1- C6alkyl); C1-C6alkyl; C1-C6haloalkyl; C1-C6alkoxy; C1-C6haloalkoxy; C6-C14aryl optionally substituted with one or more substituents independently selected from halo, COOH, SF5, S(O)2NH2, S(O)2(C1-C6alkyl), S(O)(NH)CH3, P(O)(OH)2, P(O)(OH)CH3, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C3-C6 carbocyclyl; C6-C14 aryloxy; C3-C6 cycloalkyl; C3-C6 cycloalkyloxy; (C3-C8 cycloalkyl)(C1-C6 alkyl); (C6-C14 aryl)(C1-C6 alkyl); 5- or 6-membered heterocyclyl containing 1, 2, or 3 ring atoms independently selected from N, O, and S; and 5- or 6-membered heteroaryl containing 1, 2, or 3 ring atoms independently selected from N, O, and S and optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and C1-C6 haloalkyl.

2. The compound of claim 1, where the compound is of Formula (I”): , or a pharmaceutically acceptable 3. The compound of claim 1 or 2, wherein A .

4. The compound of claim 3, wherein X3is N.

5. The compound of claim 4, wherein X3is CH or CNH2.

6. The compound of any one of claims 3-5, wherein X5is N. ALXN-0780-PCT01-NP 7. The compound of any one of claims 3-5, wherein X5is CH, C(CH3), or CNH2.

8. The compound of any one of claims 3-7, wherein X4is N.

9. The compound of claim 1 or 2, wherein A is .

10. The compound of claim 9, wherein X3is N, and X4is CH2or N.

11. The compound of claim 9, wherein X3is CH2, and X4is N.

12. The compound of any one of claims 3-11, wherein X1is S.

13. The compound of any one of claims 3-11, wherein X1is NH, NCH3, NCH2CH3, NCHF2, or N(cyclopropyl).

14. The compound of any one of claims 3-13, wherein R6is H or F.

15. The compound of any one of claims 3-14, wherein R7is H, Cl, CH3, or cyclopropyl.

16. The compound of any one of claims 1-15, wherein R1and R1’are both H.

17. The compound of any one of claims 1-16, wherein R2is H or methyl and R2’is H or methyl.

18. The compound of any one of claims 1-17, wherein R3is H.

19. The compound of any one of claims 1-18, wherein R3is 5- to 10-membered heteroaryl containing 1, 2, or 3 ring atoms independently selected from N, O, and S and optionally substituted with one or more substituents selected from halo, C1-C6alkyl, C1-C6haloalkyl, (C1-C6alkoxy)(C1-C6alkyl), and 5- or 6- membered heterocycloalkyl containing 1, 2, or 3 ring atoms independently selected from N, O, and S.

20. The compound of claim 19, wherein R3is 5-membered heteroaryl containing 1 or 2 ring atoms independently selected from N, O, and S and optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, C1-C6 haloalkyl, (C1-C6 alkoxy)(C1-C6 alkyl), and 5- or 6- membered heterocycloalkyl containing 1 or 2 ring atoms independently selected from N and O. ALXN-0780-PCT01-NP 21. The compound of claim 19, wherein R3is 6-membered heteroaryl containing 1 or 2 ring atoms independently selected from N, O, and S and optionally substituted with one or more substituents independently selected from halo and C1-C6alkyl.

22. The compound of any one of claims 1-18, wherein R3is 6-membered heterocycloalkyl containing 1 or 2 ring atoms independently selected from N and O and optionally substituted with C1-C6alkyl.

23. The compound of any one of claims 1-18, wherein X is C(Rg)2.

24. The compound of claim 23, wherein X is CH2or CHCH3.

25. The compound of claim 23, wherein both Rg, together with the carbon with which they are attached, form spirocyclic cyclopropyl.

26. The compound of any one of claims 1-18, wherein X is O or S.

27. The compound of any one of claims 1-26, wherein R4and R4’are both H.

28. The compound of any one of claims 1-27, wherein R5is H or CH3.

29. The compound of any one of claims 1-28, wherein L is a bond, -CH2-, or -(CH2)2- .

30. The compound of any one of claims 1-29, wherein B is phenyl optionally substituted with one or more substituents independently selected from halo; cyano; COORh, wherein Rhis C1-C6 alkyl; S(O)2(C1- C6alkyl); C1-C6 alkyl; C1-C6 haloalkyl; C1-C6 alkoxy; C1-C6 haloalkoxy; phenyl optionally substituted with one or more halo; phenoxy; C3-C6cycloalkyl; C3-C6cycloalkyloxy; 5- or 6-membered heterocyclyl containing 1 or 2 ring atoms independently selected from N and O; and 5- or 6-membered heteroaryl containing 1, 2, or 3 ring atoms independently selected from N, O, and S and optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and C1-C6 haloalkyl.

31. The compound of any one of claims 1-29, wherein B is naphthyl optionally substituted with one or more substituents independently selected from halo and C1-C6 alkoxy.

32. The compound of any one of claims 1-29, wherein B is C3-C14carbocyclyl optionally substituted with phenyl.

33. The compound of any one of claims 1-29, wherein B is 5- to 14-membered heterocyclyl containing 1 or 2 oxygen atoms. ALXN-0780-PCT01-NP 33. The compound of any one of claims 1-29, wherein B is 5- to 10-membered heteroaryl containing 1, 2, or 3 ring atoms independently selected from N, O, and S; wherein B is optionally substituted with one or more substituents independently selected from halo; C1-C6alkyl; C1-C6haloalkyl; C1-C6alkoxy; phenyl optionally substituted with one or more substituents selected from halo, COOH, S(O)2NH2, S(O)2(C1- C6alkyl), C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C3-C6 cycloalkyl; C3-C6 carbocyclyl; (C3-C6 cycloalkyl)(C1-C6alkyl); phenyl(C1-C6alkyl); 5- or 6-membered heterocyclyl containing 1 or 2 ring atoms independently selected from N and O; and 5- or 6-membered heteroaryl containing 1 or 2 ring atoms independently selected from N and O and optionally substituted with one or more halo.

34. A compound of Table 1, or a pharmaceutically acceptable salt thereof.

35. The compound of any one of claims 1-34, having C1 esterase (C1s) inhibiting activity.

36. A pharmaceutical comprising a compound of any one of claims 1-35 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

37. A method of treating a C1s mediated disorder, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of any one of claims 1-35 or a pharmaceutically acceptable salt thereof.

38. A method of inhibiting C1s activity in a subject having a C1s mediated disorder, comprising administering to the subject a therapeutically effective amount of a compound of any one of claims 1-35 or a pharmaceutically acceptable salt thereof.

39. The method of claim 37 or 38, where in the subject is a human.

40. The method of any one of claims 37-39, wherein is the disorder is acute antibody-mediated rejection, amyotrophic lateral sclerosis, autoimmune blistering disease, bullous pemphigoid, chronic inflammatory demyelinating polyneuropathy, geographic atrophy, Guillain-Barré Syndrome, Huntington’s Disease, immune thrombocytopenia purpura, lupus nephritis, multifocal motor neuropathy, rheumatoid arthritis, traumatic brain injury, or warm autoimmune hemolytic anemia.

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