MACROCYCLIC COMPOUNDS INCORPORATION BY REFERENCE TO ANY PRIORITY APPLICATIONS [0001] Any and all applications for which a foreign or domestic priority claim is identified, for example, in the Application Data Sheet or Request as filed with the present application, are hereby incorporated by reference under 37 CFR 1.57, and Rules 4.18 and 20.6, including U.S. Provisional Application Nos.63/202,156, filed May 28, 2021 and 63/202,158, filed May 28, 2021. Field [0002] The present application relates to compounds that are Mcl-1 inhibitors and methods of using them to treat conditions characterized by excessive cellular proliferation, such as cancer. Description [0003] Mcl-1 (myeloid cell leukemia-1) is a member of the Bcl-2 family of proteins. MCL-1 is widely expressed in human tissues and is primarily located in the mitochondria in cells. Upregulation of Mcl-1 occurs in different cancer types. Additionally, overexpression of Mcl-1 has been linked to drug resistance to several cancer therapies. SUMMARY [0004] Some embodiments provide a compound of Formula (I), or a pharmaceutically acceptable salt thereof. Some embodiments provide a compound of Formula (II), or a pharmaceutically acceptable salt thereof. [0005] Some embodiments disclosed herein relate to a pharmaceutical composition that can include an effective amount of one or more of compounds of Formula (I) and/or one or more compounds of Formula (II), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent, excipient or combination thereof. [0006] Some embodiments described herein relate to a method for ameliorating and/or treating a cancer described herein that can include administering an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) or a pharmaceutical composition that includes an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) to a subject having a cancer described herein. Other embodiments described herein relate to the use of an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) or a pharmaceutical composition that includes an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) in the manufacture of a medicament for ameliorating and/or treating a cancer described herein. Still other embodiments described herein relate to an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) or a pharmaceutical composition that includes an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) for ameliorating and/or treating a cancer described herein. [0007] Some embodiments described herein relate to a method for inhibiting replication of a malignant growth or a tumor that can include contacting the growth or the tumor with an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) or a pharmaceutical composition that includes an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing), wherein the malignant growth or tumor is due to a cancer described herein. Other embodiments described herein relate to the use of an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) or a pharmaceutical composition that includes an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) in the manufacture of a medicament for inhibiting replication of a malignant growth or a tumor, wherein the malignant growth or tumor is due to a cancer described herein. Still other embodiments described herein relate to an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) or a pharmaceutical composition that includes an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) for inhibiting replication of a malignant growth or a tumor, wherein the malignant growth or tumor is due to a cancer described herein. [0008] Some embodiments described herein relate to a method for ameliorating or treating a cancer described herein that can include contacting a malignant growth or a tumor with an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) or a pharmaceutical composition that includes an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) to a subject having a cancer described herein. Other embodiments described herein relate to the use of an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) or a pharmaceutical composition that includes an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) in the manufacture of a medicament for ameliorating or treating a cancer described herein that can include contacting a malignant growth or a tumor, wherein the malignant growth or tumor is due to a cancer described herein. Still other embodiments described herein relate to an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) or a pharmaceutical composition that includes an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) for ameliorating or treating a cancer described herein that can include contacting a malignant growth or a tumor, wherein the malignant growth or tumor is due to a cancer described herein. [0009] Some embodiments described herein relate to a method for inhibiting the activity of Mcl-1 in a cell that can include providing an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) or a pharmaceutical composition that includes an effective amount of a compound described herein (for example, a compound of Formula (I), or a pharmaceutically acceptable salt of any of the foregoing) to a cancer cell from a cancer described herein. Other embodiments described herein relate to the use of an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) or a pharmaceutical composition that includes an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) in the manufacture of a medicament for inhibiting the activity of Mcl-1. Still other embodiments described herein relate to an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) or a pharmaceutical composition that includes an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) for inhibiting the activity of Mcl-1. [0010] Some embodiments described herein relate to a method for ameliorating or treating a cancer described herein that can include inhibiting the activity of Mcl-1 using an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) or a pharmaceutical composition that includes an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing). Other embodiments described herein relate to the use of an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) or a pharmaceutical composition that includes an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) in the manufacture of a medicament for ameliorating or treating a cancer described herein by inhibiting the activity of Mcl-1. Still other embodiments described herein relate to an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) or a pharmaceutical composition that includes an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) for ameliorating or treating a cancer described herein by inhibiting the activity of Mcl-1. DETAILED DESCRIPTION [0011] Myeloid Cell Leukemia 1 (Mcl-1) is an important anti-apoptotic member of the BCL-2 family of proteins and a master regulator of cell survival. Amplification of the MCL1 gene and/or overexpression of the Mcl-1 protein has been observed in multiple cancer types and is commonly implicated in tumor development. MCL1 is one of the most frequently amplified genes in human cancers. In many malignancies, Mcl-1 is a critical survival factor and it has been shown to mediate drug resistance to a variety of anti-cancer agents. Mcl-1 promotes cell survival by binding to pro-apoptotic proteins like Bim, Noxa, Bak, and Bax and neutralizing their death- inducing activities. Inhibition of Mcl-1 thereby releases these pro-apoptotic proteins, often leading to the induction of apoptosis in tumor cells dependent on Mcl-1 for survival. Therapeutically targeting Mcl-1 alone or in combination with other therapies, therefore, is a promising strategy to treat a multitude of malignancies and to overcome drug resistance in several human cancers. Definitions [0012] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of ordinary skill in the art. All patents, applications, published applications and other publications referenced herein are incorporated by reference in their entirety unless stated otherwise. In the event that there are a plurality of definitions for a term herein, those in this section prevail unless stated otherwise. [0013] As used herein, “Ca to Cb” in which “a” and “b” are integers refer to the number of carbon atoms in a group. The indicated group can contain from “a” to “b”, inclusive, carbon atoms. Thus, for example, a “C ₁ to C ₄ alkyl” group refers to all alkyl groups having from 1 to 4 carbons, that is, CH3-, CH3CH2-, CH3CH2CH2-, (CH3)2CH-, CH3CH2CH2CH2-, CH3CH2CH(CH3)- and (CH3)3C-. If no “a” and “b” are designated, the broadest range described in these definitions is to be assumed. [0014] As used herein, the term “alkyl” refers to a fully saturated aliphatic hydrocarbon group. The alkyl moiety may be branched or straight chain. Examples of branched alkyl groups include, but are not limited to, iso-propyl, sec-butyl, iso-butyl, t-butyl and the like. Examples of straight chain alkyl groups include, but are not limited to, methyl, ethyl, n-propyl and n-butyl. An alkyl group may be substituted or unsubstituted. [0015] As used herein, “cycloalkyl” refers to a completely saturated (no double or triple bonds) hydrocarbon ring(s). Examples of mono-cycloalkyl groups include, but are in no way limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. A cycloalkyl group may be unsubstituted or substituted. [0016] As used herein, “aryl” refers to a carbocyclic (all carbon) monocyclic or multicyclic aromatic ring system (including fused ring systems where two carbocyclic rings share a chemical bond) that has a fully delocalized pi-electron system throughout all the rings. The number of carbon atoms in an aryl group can vary. For example, the aryl group can be a C ₆ -C ₁₄ aryl group, a C6-C10 aryl group or a C6 aryl group. Examples of aryl groups include, but are not limited to, benzene, naphthalene and azulene. An aryl group may be substituted or unsubstituted. [0017] As used herein, “heteroaryl” refers to a monocyclic or multicyclic aromatic ring system (a ring system with fully delocalized pi-electron system) that contain(s) one or more heteroatoms (for example, 1, 2 or 3 heteroatoms), that is, an element other than carbon, including but not limited to, nitrogen, oxygen and sulfur. The number of atoms in the ring(s) of a heteroaryl group can vary. For example, the heteroaryl group can contain 4 to 14 atoms in the ring(s), 5 to 10 atoms in the ring(s) or 5 to 6 atoms in the ring(s), such as nine carbon atoms and one heteroatom; eight carbon atoms and two heteroatoms; seven carbon atoms and three heteroatoms; eight carbon atoms and one heteroatom; seven carbon atoms and two heteroatoms; six carbon atoms and three heteroatoms; five carbon atoms and four heteroatoms; five carbon atoms and one heteroatom; four carbon atoms and two heteroatoms; three carbon atoms and three heteroatoms; four carbon atoms and one heteroatom; three carbon atoms and two heteroatoms; or two carbon atoms and three heteroatoms. Furthermore, the term “heteroaryl” includes fused ring systems where two rings, such as at least one aryl ring and at least one heteroaryl ring or at least two heteroaryl rings, share at least one chemical bond. Examples of heteroaryl rings include, but are not limited to, furan, furazan, thiophene, benzothiophene, phthalazine, pyrrole, oxazole, benzoxazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, thiazole, 1,2,3-thiadiazole, 1,2,4-thiadiazole, benzothiazole, imidazole, benzimidazole, indole, indazole, pyrazole, benzopyrazole, isoxazole, benzoisoxazole, isothiazole, triazole, benzotriazole, thiadiazole, tetrazole, pyridine, pyridazine, pyrimidine, pyrazine, purine, pteridine, quinoline, isoquinoline, quinazoline, quinoxaline, cinnoline and triazine. A heteroaryl group may be substituted or unsubstituted. [0018] As used herein, “heterocyclyl” refers to three-, four-, five-, six-, seven-, eight-, nine-, ten-, up to 18-membered monocyclic, bicyclic and tricyclic ring system wherein carbon atoms together with from 1 to 5 heteroatoms constitute said ring system. A heterocycle may optionally contain one or more unsaturated bonds situated in such a way, however, that a fully delocalized pi-electron system does not occur throughout all the rings. The heteroatom(s) is an element other than carbon including, but not limited to, oxygen, sulfur and nitrogen. A heterocycle may further contain one or more carbonyl or thiocarbonyl functionalities, so as to make the definition include oxo-systems and thio-systems such as lactams, lactones, cyclic imides, cyclic thioimides and cyclic carbamates. When composed of two or more rings, the rings may be joined together in a fused, bridged or spiro fashion. As used herein, the term “fused” refers to two rings which have two atoms and one bond in common. As used herein, the term “bridged heterocyclyl” refers to compounds wherein the heterocyclyl contains a linkage of one or more atoms connecting non-adjacent atoms. As used herein, the term “spiro” refers to two rings which have one atom in common and the two rings are not linked by a bridge. Heterocyclyl group can contain 3 to 30 atoms in the ring(s), 3 to 20 atoms in the ring(s), 3 to 10 atoms in the ring(s), 3 to 8 atoms in the ring(s) or 3 to 6 atoms in the ring(s). For example, five carbon atoms and one heteroatom; four carbon atoms and two heteroatoms; three carbon atoms and three heteroatoms; four carbon atoms and one heteroatom; three carbon atoms and two heteroatoms; two carbon atoms and three heteroatoms; one carbon atom and four heteroatoms; three carbon atoms and one heteroatom; or two carbon atoms and one heteroatom. Additionally, any nitrogens in a heterocyclyl may be quaternized. Heterocyclyl groups may be unsubstituted or substituted. Examples of such “heterocyclyl” groups include but are not limited to, 1,3-dioxin, 1,3-dioxane, 1,4-dioxane, 1,2- dioxolane, 1,3-dioxolane, 1,4-dioxolane, 1,3-oxathiane, 1,4-oxathiin, 1,3-oxathiolane, 1,3- dithiole, 1,3-dithiolane, 1,4-oxathiane, tetrahydro-1,4-thiazine, 2H-1,2-oxazine, maleimide, succinimide, barbituric acid, thiobarbituric acid, dioxopiperazine, hydantoin, dihydrouracil, trioxane, hexahydro-1,3,5-triazine, imidazoline, imidazolidine, isoxazoline, isoxazolidine, oxazoline, oxazolidine, oxazolidinone, thiazoline, thiazolidine, morpholine, oxirane, piperidine N- Oxide, piperidine, piperazine, pyrrolidine, azepane, pyrrolidone, pyrrolidione, 4-piperidone, pyrazoline, pyrazolidine, 2-oxopyrrolidine, tetrahydropyran, 4H-pyran, tetrahydrothiopyran, thiomorpholine, thiomorpholine sulfoxide, thiomorpholine sulfone and their benzo-fused analogs (e.g., benzimidazolidinone, tetrahydroquinoline and/or 3,4-methylenedioxyphenyl). Examples of spiro heterocyclyl groups include 2-azaspiro[3.3]heptane, 2-oxaspiro[3.3]heptane, 2-oxa-6- azaspiro[3.3]heptane, 2,6-diazaspiro[3.3]heptane, 2-oxaspiro[3.4]octane and 2- azaspiro[3.4]octane. [0019] As used herein, “aryl(alkyl)” refer to an aryl group connected, as a substituent, via a lower alkylene group. The lower alkylene and aryl group of an aryl(alkyl) may be substituted or unsubstituted. Examples include but are not limited to benzyl, 2-phenylalkyl, 3-phenylalkyl and naphthylalkyl. [0020] As used herein, “lower alkylene groups” are straight-chained -CH ₂ - tethering groups, forming bonds to connect molecular fragments via their terminal carbon atoms. Examples include but are not limited to methylene (-CH2-), ethylene (-CH2CH2-), propylene (-CH2CH2CH2- ) and butylene (-CH2CH2CH2CH2-). A lower alkylene group can be substituted by replacing one or more hydrogen of the lower alkylene group and/or by substituting both hydrogens on the same carbon with a cycloalkyl group (e.g. ). [0021] The term “halogen” as used herein, means any one of the radio-stable atoms of column 7 of the Periodic Table of the Elements, such as, fluorine, chlorine, bromine and iodine. [0022] As used herein, “haloalkyl” refers to an alkyl group in which one or more of the hydrogen atoms are replaced by a halogen (e.g., mono-haloalkyl, di-haloalkyl, tri-haloalkyl and polyhaloalkyl). Such groups include but are not limited to, chloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, 1-chloro-2-fluoromethyl, 2-fluoroisobutyl and pentafluoroethyl. A haloalkyl may be substituted or unsubstituted. [0023] As used herein, “hydroxyalkyl” refer to an alkyl as described herein that includes 1, 2 or 3 hydroxy (–OH) groups attached to the alkyl. [0024] The term “halogen atom” or “halogen” as used herein, means any one of the radio-stable atoms of column 7 of the Periodic Table of the Elements, such as, fluorine, chlorine, bromine and iodine. [0025] Where the number of substituents is not specified (e.g. haloalkyl), there may be one or more substituents present. For example, “haloalkyl” may include one or more of the same or different halogens. As another example, “C ₁ -C ₃ alkoxyphenyl” may include one or more of the same or different alkoxy groups containing one, two or three atoms. [0026] As used herein, a radical indicates species with a single, unpaired electron such that the species containing the radical can be covalently bonded to another species. Hence, in this context, a radical is not necessarily a free radical. Rather, a radical indicates a specific portion of a larger molecule. The term “radical” can be used interchangeably with the term “group.” [0027] The term “pharmaceutically acceptable salt” refers to a salt of a compound that does not cause significant irritation to an organism to which it is administered and does not abrogate the biological activity and properties of the compound. In some embodiments, the salt is an acid addition salt of the compound. Pharmaceutical salts can be obtained by reacting a compound with inorganic acids such as hydrohalic acid (e.g., hydrochloric acid or hydrobromic acid), a sulfuric acid, a nitric acid and a phosphoric acid (such as 2,3-dihydroxypropyl dihydrogen phosphate). Pharmaceutical salts can also be obtained by reacting a compound with an organic acid such as aliphatic or aromatic carboxylic or sulfonic acids, for example formic, acetic, succinic, lactic, malic, tartaric, citric, ascorbic, nicotinic, methanesulfonic, ethanesulfonic, p- toluenesulfonic, trifluoroacetic, benzoic, salicylic, 2-oxopentanedioic or naphthalenesulfonic acid. Pharmaceutical salts can also be obtained by reacting a compound with a base to form a salt such as an ammonium salt, an alkali metal salt, such as a sodium, a potassium or a lithium salt, an alkaline earth metal salt, such as a calcium or a magnesium salt, a salt of a carbonate, a salt of a bicarbonate, a salt of organic bases such as dicyclohexylamine, N-methyl-D-glucamine, tris(hydroxymethyl)methylamine, C ₁ -C ₇ alkylamine, cyclohexylamine, triethanolamine, ethylenediamine and salts with amino acids such as arginine and lysine. For compounds of Formula (I), those skilled in the art understand that when a salt is formed by protonation of a nitrogen-based group (for example, NH ₂ ), the nitrogen-based group can be associated with a positive charge (for example, NH2 can become NH3 ⁺ ) and the positive charge can be balanced by a negatively charged counterion (such as Cl-). [0028] It is understood that, in any compound described herein having one or more chiral centers, if an absolute stereochemistry is not expressly indicated, then each center may independently be of R-configuration or S-configuration or a mixture thereof. Thus, the compounds provided herein may be enantiomerically pure, enantiomerically enriched, racemic mixture, diastereomerically pure, diastereomerically enriched or a stereoisomeric mixture. In addition, it is understood that, in any compound described herein having one or more double bond(s) generating geometrical isomers that can be defined as E or Z, each double bond may independently be E or Z a mixture thereof. Likewise, it is understood that, in any compound described, all tautomeric forms are also intended to be included. [0029] It is to be understood that where compounds disclosed herein have unfilled valencies, then the valencies are to be filled with hydrogens or isotopes thereof, e.g., hydrogen-1 (protium) and hydrogen-2 (deuterium). [0030] It is understood that the compounds described herein can be labeled isotopically. Substitution with isotopes such as deuterium may afford certain therapeutic advantages resulting from greater metabolic stability, such as, for example, increased in vivo half- life or reduced dosage requirements. Each chemical element as represented in a compound structure may include any isotope of said element. For example, in a compound structure a hydrogen atom may be explicitly disclosed or understood to be present in the compound. At any position of the compound that a hydrogen atom may be present, the hydrogen atom can be any isotope of hydrogen, including but not limited to hydrogen-1 (protium) and hydrogen-2 (deuterium). Thus, reference herein to a compound encompasses all potential isotopic forms unless the context clearly dictates otherwise. [0031] It is understood that the methods and combinations described herein include crystalline forms (also known as polymorphs, which include the different crystal packing arrangements of the same elemental composition of a compound), amorphous phases, salts, solvates and hydrates. In some embodiments, the compounds described herein exist in solvated forms with pharmaceutically acceptable solvents such as water, ethanol or the like. In other embodiments, the compounds described herein exist in unsolvated form. Solvates contain either stoichiometric or non-stoichiometric amounts of a solvent, and may be formed during the process of crystallization with pharmaceutically acceptable solvents such as water, ethanol or the like. Hydrates are formed when the solvent is water or alcoholates are formed when the solvent is alcohol. In addition, the compounds provided herein can exist in unsolvated as well as solvated forms. In general, the solvated forms are considered equivalent to the unsolvated forms for the purposes of the compounds and methods provided herein. [0032] Where a range of values is provided, it is understood that the upper and lower limit, and each intervening value between the upper and lower limit of the range is encompassed within the embodiments. [0033] Terms and phrases used in this application, and variations thereof, especially in the appended claims, unless otherwise expressly stated, should be construed as open ended as opposed to limiting. As examples of the foregoing, the term ‘including’ should be read to mean ‘including, without limitation,’ ‘including but not limited to,’ or the like; the term ‘comprising’ as used herein is synonymous with ‘including,’ ‘containing,’ or ‘characterized by,’ and is inclusive or open-ended and does not exclude additional, unrecited elements or method steps; the term ‘having’ should be interpreted as ‘having at least;’ the term ‘includes’ should be interpreted as ‘includes but is not limited to;’ the term ‘example’ is used to provide exemplary instances of the item in discussion, not an exhaustive or limiting list thereof; and use of terms like ‘preferably,’ ‘preferred,’ ‘desired,’ or ‘desirable,’ and words of similar meaning should not be understood as implying that certain features are critical, essential, or even important to the structure or function, but instead as merely intended to highlight alternative or additional features that may or may not be utilized in a particular embodiment. In addition, the term “comprising” is to be interpreted synonymously with the phrases "having at least" or "including at least". When used in the context of a compound, composition or device, the term "comprising" means that the compound, composition or device includes at least the recited features or components, but may also include additional features or components. [0034] With respect to the use of substantially any plural and/or singular terms herein, those having skill in the art can translate from the plural to the singular and/or from the singular to the plural as is appropriate to the context and/or application. The various singular/plural permutations may be expressly set forth herein for sake of clarity. The indefinite article “a” or “an” does not exclude a plurality. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage. Any reference signs in the claims should not be construed as limiting the scope. Compounds – Formula (I) [0035] Some embodiments disclosed herein relate to a compound of Formula (I), or a pharmaceutically acceptable salt thereof, having the structure: I) wherein: R ¹ , R ² and R ³ can be eac en, an unsubstituted C1-4 alkyl or an unsubstituted C _1-4 haloalkyl; R ⁴ can be hydrogen, an unsubstituted C _1-4 alkyl, an optionally substituted C _3-6 monocyclic cycloalkyl or an unsubstituted C _1-4 haloalkyl, wherein when the C _3-6 monocyclic cycloalkyl is substituted, the C3-6 monocyclic cycloalkyl can be substituted with 1 or 2 halogens; Z can be CH ₂ , CH or NH; wherein when Z is CH ₂ , then each ---- is a single bond; wherein when Z is CH, then each ---- is a double bond; and wherein when Z is NH, then each ---- is a single bond; each R ⁵ can be independently halogen or an optionally substituted C1-4 alkyl, wherein when the C1-4 alkyl is substituted, the C1-4 alkyl is substituted with 1 or 2 halogens; Ring A ca X ¹ can be hydrogen, an unsubstituted C1-4 alkyl, an o kyl or an unsubstituted C _1-4 haloalkyl, wherein when the C3-6 monocyclic cycloalkyl is substituted, the C3-6 monocyclic cycloalkyl is substituted with 1 or 2 halogens; wherein when Rin , then X ² can be absent; and X ³ can be an unsubstituted C1-4 alkyl, C1-4 hy yl, methoxypropyl or –C1-4 alkyl- NR ^a R ^b ; wherein when Rin , then X ² can be an unsubstituted C1-4 alkyl, C1- 4 hydroxyalkyl, methoxyet –C _1-4 alkyl-NR ^a R ^b ; and X ³ can be absent; R ^a and R ^b can be each independently hydrogen or an unsubstituted C1-4 alkyl; Y ¹ can be O (oxygen), S (sulfur), CH2, CF2 or NR ⁶ ; R ⁶ can be selected from hydrogen, an unsubstituted C1-4 alkyl, an optionally substituted monocyclic C _3-6 cycloalkyl, C _1-4 hydroxyalkyl, –C(=O)R ⁷ and –S(=O) ₂ R ⁸ , wherein when the C3-6 monocyclic cycloalkyl is substituted, the C3-6 monocyclic cycloalkyl is substituted with 1 or 2 halogens; R ⁷ can be selected from an unsubstituted C1-4 alkyl, an unsubstituted halo-C _1-4 alkyl, an optionally substituted monocyclic C _3-6 cycloalkyl, an optionally substituted C _6-10 aryl, an optionally substituted 5- to 10-membered heteroaryl, an optionally substituted 4- to 8-membered heterocyclyl and an optionally substituted C6-10 aryl(C1-4 alkyl); R ⁸ can be selected from an unsubstituted C _1-4 alkyl, an unsubstituted halo-C _1-4 alkyl, an optionally substituted monocyclic C _3-6 cycloalkyl, an optionally substituted C _6-10 aryl, an optionally substituted 5- to 10-membered heteroaryl, an optionally substituted 4- to 8-membered heterocyclyl and an optionally substituted C _6-10 aryl(C _1-4 alkyl); wherein when R ⁷ and R ⁸ are substituted, then R ⁷ and R ⁸ can be independently substituted with 1 or more substituents selected from halogen, an unsubstituted C1-4 alkyl and an unsubstituted C1-4 haloalkyl; Ring B can be selected from 2 can be an optionally substituted uted with 1 or more substituents independently selected from halogen and an unsubstituted C _1-4 alkyl; Y ³ can be O (oxygen), S (sulfur), CH2 or CF2; and m can be 0, 1, 2 or 3. [0036] The phenyl ring of the indole of Formula (I) can be unsubstituted or substituted. In some embodiments, R ¹ , R ² and R ³ can each be hydrogen. When the phenyl ring of the indole ring is substituted, the phenyl ring can be mono-, di- or tri-substituted. In some embodiments, R ¹ can be halogen (such as fluoro or chloro). In other embodiments, R ¹ can be an unsubstituted C1-4 alkyl. Examples of unsubstituted C _1-4 alkyls include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl and tert-butyl. In still other embodiments, R ¹ can be an unsubstituted C1-4 haloalkyl, such as CF ₃ and CHF ₂ . In some embodiments, R ² can be hydrogen. In other embodiments, R ² can be halogen, including those described herein. In still other embodiments, R ² can be an unsubstituted C1-4 alkyl, such as those described herein. In yet still other embodiments, R ² can be an unsubstituted C _1-4 haloalkyl. In some embodiments, R ³ can be hydrogen. In other embodiments, R ³ can be halogen, such as F or Cl. In still other embodiments, R ³ can be an unsubstituted C1-4 alkyl (for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl and tert-butyl). In yet still other embodiments, R ³ can be an unsubstituted C _1-4 haloalkyl. In some embodiments, R ¹ can be halogen, an unsubstituted C1-4 alkyl or an unsubstituted C1-4 haloalkyl; and R ² and R ³ can be each hydrogen. In other embodiments, R ¹ and R ³ can be independently halogen, an unsubstituted C1-4 alkyl or an unsubstituted C _1-4 haloalkyl; and R ² can be hydrogen. [0037] The 5-membered ring of the indole can be unsubstituted or substituted. In some embodiments, R ⁴ can be hydrogen. In other embodiments, R ⁴ can be an unsubstituted C1-4 alkyl. Suitable C1-4 alkyls are described herein and include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl and tert-butyl. In some embodiments, R ⁴ can be an unsubstituted C _3-6 monocyclic cycloalkyl. In other embodiments, R ⁴ can be a substituted C3-6 monocyclic cycloalkyl substituted with 1 or 2 halogens (for example, fluoro or chloro). Examples of C3-6 monocyclic cycloalkyls include cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. In still other embodiments, R ⁴ can be an unsubstituted C1-4 haloalkyl, such as CHF2 and CF3. [0038] In other embodiments, Z can be CH2; and each ---- can be a single bond. In other embodiments, Z can be CH; and each ---- can be a double bond. In still other embodiments, Z can be NH; and each ---- can be a single bond. Examples of the bicyclic ring that includes Z are . ents, m can be 0, such that upper ring is unsubstituted. In other embodiments, m can be 1, wherein R ⁵ can be halogen or an unsubstituted substituted C _1-4 alkyl. In still other embodiments, m can be 2, wherein each R ⁵ can be independently halogen or an unsubstituted substituted C1-4 alkyl. In yet still other embodiments, m can be 3, wherein each R ⁵ can be independently halogen or an unsubstituted substituted C1-4 alkyl. Suitable halogens (including fluoro and chloro) and an optionally substituted C _1-4 alkyls (optionally substituted versions of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl and tert-butyl). In some embodiments, each R ⁵ can be independently an unsubstituted C1-4 alkyl. [0040] In some embodiments, Y ¹ can be O (oxygen). In other embodiments, Y ¹ can be S (sulfur). In still other embodiments, Y ¹ can be CH ₂ . In yet still other embodiments, Y ¹ can be CF2. In some embodiments, Y ¹ can be NR ⁶ , wherein R ⁶ can be hydrogen. In other embodiments, Y ¹ can be NR ⁶ , wherein R ⁶ can be an unsubstituted C1-4 alkyl. For example, R ⁶ can be methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl. In still other embodiments, Y ¹ can be NR ⁶ , wherein R ⁶ can be an unsubstituted monocyclic C3-6 cycloalkyl. In yet still other embodiments, Y ¹ can be NR ⁶ , wherein R ⁶ can be a substituted monocyclic C3-6 cycloalkyl substituted with 1 or 2 halogens. Suitable halogens include, but are not limited to, fluoro and chloro. In some embodiments, Y ¹ can be NR ⁶ , wherein R ⁶ can be C _1-4 hydroxyalkyl. Exemplary C1-4 hydroxyalkyls include the following: HOCH2–, HOCH2CH2–, HOCH2CH2CH2–, HOCH2CH2CH2CH2–, CH3CH2CH(OH)–, CH3CH(OH) CH2– and HOCH2CH(OH)–. In other embodiments, Y ¹ can be NR ⁶ , wherein R ⁶ can be –C(=O)R ⁷ , wherein R ⁷ can be selected from an unsubstituted C1-4 alkyl, an unsubstituted halo-C1-4 alkyl, an optionally substituted monocyclic C3- 6 cycloalkyl, an optionally substituted C6-10 aryl, an optionally substituted 5- to 10-membered heteroaryl, an optionally substituted 4- to 8-membered heterocyclyl and an optionally substituted C6-10 aryl(C1-4 alkyl). In still other embodiments, Y ¹ can be NR ⁶ , wherein R ⁶ can be –S(=O)2R ⁸ , R ⁸ can be selected from an unsubstituted C1-4 alkyl, an unsubstituted halo-C1-4 alkyl, an optionally substituted monocyclic C _3-6 cycloalkyl, an optionally substituted C _6-10 aryl, an optionally substituted 5- to 10-membered heteroaryl, an optionally substituted 4- to 8-membered heterocyclyl and an optionally substituted C6-10 aryl(C1-4 alkyl). When R ⁷ and R ⁸ are substituted, then R ⁷ and R ⁸ can be independently substituted with 1 or more substituents selected from halogen, an unsubstituted C _1-4 alkyl and an unsubstituted C _1-4 haloalkyl. For example, when R ⁷ and R ⁸ are substituted, R ⁷ and/or R ⁸ can be substituted 1, 2 or 3 times with a substituent selected from halogen (such as F or Cl), an unsubstituted C1-4 alkyl (for example, methyl, ethyl, n-propyl, iso-propyl, n- butyl, iso-butyl, sec-butyl and tert-butyl) and an unsubstituted C _1-4 haloalkyl (such as such as CF ₃ and CHF2). [0041] Examples of R ⁷ and R ⁸ groups include the following: methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, –CF ₃ , –CHF ₂ , –CH ₂ F, –CCl ₃ , –CHCl ₂ , –CH ₂ Cl,

embodiments, Y ² can be a substituted C1-4 alkylene, wherein when Y ² can be substituted, each substituent can be independently halogen or an unsubstituted C _1-4 alkyl. Exemplary optionally substituted C _1-4 alkylenes for Y ² include: –CH ₂ –, –CH ₂ CH ₂ –, –CH ₂ CH ₂ CH ₂ –, –CH2CH2CH2CH2–, –CH(CH3)CH2CH2–, –CHFCH2CH2– and –CH2CF2CH2–. [0043] In some embodiments, Y ³ can be O (oxygen). In other embodiments, Y ³ can be S (sulfur). In still other embodiments, Y ³ can be CH ₂ . In yet still other embodiments, Y ³ can be CF2. [0044] In some embodiments, Ring A can be . In other embodiments, Ring A can be . As provided herein, X ¹ can be hydrogen, an unsubstituted C1-4 alkyl, an op d C3-6 monocyclic cycloalkyl or an unsubstituted C _1-4 haloalkyl, wherein when the C _3-6 monocyclic cycloalkyl is substituted, the C _3-6 monocyclic cycloalkyl is substituted with 1 or 2 halogens. In some embodiments, X ¹ can be hydrogen. In other embodiments, X ¹ can be an unsubstituted C1-4 alkyl. Exemplary C1-4 alkyls include methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl and tert-butyl. In some embodiments, X ¹ can be an unsubstituted C3-6 monocyclic cycloalkyl. In other embodiments, X ¹ can be a substituted C3-6 monocyclic cycloalkyl substituted with 1 or 2 halogens (for example, fluoro and chloro). Examples of suitable C _3-6 monocyclic cycloalkyls include cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, including halogen-substituted versions thereof. In some embodiments, X ¹ can be an unsubstituted C1-4 haloalkyl, including –CF3, –CHF2, –CH2F, –CCl3, –CHCl2 and –CH2Cl. [0045] In some embodiments, when Ring , then X ² can be absent; and X ³ can be an unsubstituted C1-4 alkyl, C1-4 h hyl, methoxypropyl or –C _1-4 alkyl-NR ^a R ^b ; and R ^a and R ^b are each independently hydrogen or an unsubstituted C _1-4 alkyl. In some embodiments, X ³ can be an unsubstituted C1-4 alkyl (such as methyl, ethyl, n- propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl and tert-butyl). In other embodiments, X ³ can be C _1-4 hydroxyalkyl. In still other embodiments, X ³ can be methoxyethyl (CH ₃ OCH ₂ CH ₂ –). In yet still other embodiments, X ³ can be methoxypropyl (CH ₃ OCH ₂ CH ₂ CH ₂ –). In some embodiments, X ³ can be –C1-4 alkyl-NR ^a R ^b . [0046] In other embodiments, when Rin , then X ² can be an unsubstituted C _1-4 alkyl, C _1-4 hydroxyalkyl, methoxy ^{a b} r –C _1-4 alkyl-NR R ; and X ³ can be absent; and R ^a and R ^b are each independently hydrogen or an unsubstituted C _1-4 alkyl. In some embodiments, X ² can be an unsubstituted C1-4 alkyl (such as methyl, ethyl, n- propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl and tert-butyl). In other embodiments, X ² can be C _1-4 hydroxyalkyl. In still other embodiments, X ² can be methoxyethyl (CH ₃ OCH ₂ CH ₂ –). In yet still other embodiments, X ² can be methoxypropyl (CH3OCH2CH2CH2–). In some embodiments, X ² can be –C1-4 alkyl-NR ^a R ^b . Examples of C1-4 hydroxyalkyl for X ² and/or X ³ include HOCH2–, HOCH ₂ CH ₂ –, HOCH ₂ CH ₂ CH ₂ –, HOCH ₂ CH ₂ CH ₂ CH ₂ –, CH ₃ CH ₂ CH(OH)–, CH ₃ CH(OH) CH ₂ – and HOCH ₂ CH(OH)–. In still other embodiments, X ² can be methoxyethyl (CH ₃ OCH ₂ CH ₂ –). When X ² and/or X ³ is –C1-4 alkyl-NR ^a R ^b , the –C1-4 alkyl-NR ^a R ^b can be selected from –CH2-NH2, –CH ₂ -NH(CH ₃ ), –CH ₂ -N(CH ₃ ) ₂ , – CH ₂ CH ₂ -NH ₂ , – CH ₂ CH ₂ -NH(CH ₃ ), – CH ₂ CH ₂ -N(CH ₃ ) ₂ , – CH2CH2CH2-NH2, – CH2CH2CH2-NH(CH3), – CH2CH2CH2-N(CH3)2, – CH2CH2CH2CH2-NH2, – CH2CH2CH2CH2-NH(CH3) and – CH2CH2CH2CH2-N(CH3)2. [0047] In some embodiments, Ring B ca In other embodiments, Ring B ca In sill other embodiments, Ring B ca . One skille the connectivity of these foregoing e an connect in two ways. For example, when Rin , the compound of Formula . acceptable salts thereof, include the following: a [0049] Additional examples of compounds of Formula (I), and pharmaceutically acceptable salts thereof, include the following:

and , or a pharmaceutically acceptable salt of any of the foregoing. [0050] Further examples of compounds of Formula (I), and pharmaceutically acceptable salts thereof, include the following: or [0051] In some embodiments, a compound of Formula (I), or a pharmaceutically acceptable salt thereof, a compound, or a pharmaceutically acceptable salt thereof, where when R ¹ is Cl; and Rin ; then Ring B cannot be . In some embodiments, a compound of Formula (I), or a pharmaceutically acceptable salt thereof, a compound, or a pharmaceutically acceptable salt thereof, where when R ¹ is Cl; Rin ; Ring B i , then R ² cannot be fluoro. In some embodiments, Ring A cannot be , such as and . In some embodiments, Ring A canno d . In some embodiments, R ⁶ cannot be methyl. In some embodiments, R ⁷ cannot some embodiments, R ¹ cannot be chloro. In some embodiments, R ² cannot be hydrogen. In some embodiments, R ² cannot be fluoro. In some embodiments, R ¹ cannot be chloro when R ⁶ is methyl. In some embodiments, when R ² is hydrogen; then R ¹ cannot be chloro. In other embodiments, when R ² is fluoro; then R ¹ cannot be chloro. In some embodiments, when R ² is hydrogen; and R ⁶ is methyl; then R ¹ cannot be chloro. In other embodiments, when R ² is fluoro; and R ⁶ is methyl; then R ¹ cannot be chloro. [0052] In some embodiments, a compound of Formula (I), or a pharmaceutically acceptable salt thereof, cannot a compound disclosed in WO 2018/178226 that would be encompassed by a compound of Formula (I), or a pharmaceutically acceptable salt thereof. In some embodiments, a compound of Formula (I), or a pharmaceutically acceptable salt thereof, cannot a compound disclosed in WO 2017/181625 that would be encompassed by a compound of Formula (I), or a pharmaceutically acceptable salt thereof. In some embodiments, a compound of Formula (I), or a pharmaceutically acceptable salt thereof, cannot a compound disclosed in WO 2020/103864 that would be encompassed by a compound of Formula (I), or a pharmaceutically acceptable salt thereof. In some embodiments, a compound of Formula (I), or a pharmaceutically acceptable salt thereof, cannot a compound disclosed in WO 2020/151738 that would be encompassed by a compound of Formula (I), or a pharmaceutically acceptable salt thereof. In some embodiments, a compound of Formula (I), or a pharmaceutically acceptable salt thereof, cannot a compound disclosed in WO 2020/185606 that would be encompassed by a compound of Formula (I), or a pharmaceutically acceptable salt thereof. In some embodiments, a compound of Formula (I), or a pharmaceutically acceptable salt thereof, cannot a compound disclosed in PCT Application No. PCT/US2020/045255 that would be encompassed by a compound of Formula (I), or a pharmaceutically acceptable salt thereof.

Compounds – Formula (II) [0053] Some embodiments disclosed herein relate to a compound of Formula (II), or a pharmaceutically acceptable salt thereof, having the structure: I) wherein: R ^1-1 , R ^2-1 a logen, an unsubstituted C _1-4 alkyl or an unsubstituted C _1-4 haloalkyl; R ^4-1 can be hydrogen, an unsubstituted C _1-4 alkyl, an optionally substituted C3-6 monocyclic cycloalkyl or an unsubstituted C1-4 haloalkyl, wherein when the C _3-6 monocyclic cycloalkyl is substituted, the C _3-6 monocyclic cycloalkyl is substituted with 1 or 2 halogens; R ^5-1 can be independently halogen or an optionally substituted C _1-4 alkyl, wherein when the C1-4 alkyl is substituted, the C1-4 alkyl is substituted with 1 or 2 halogens; Z ¹ can be CH2, CH or NH; wherein when Z ¹ is CH2, then each ---- can be a single bond; wherein when Z ¹ is CH, then each ---- can be a double bond; and wherein when Z ¹ is NH, then each ---- can be a single bond; Ring A ¹ can be an optionally substituted 5-membered heteroaryl; Ring B ¹ can be an optionally substituted 3-7 membered cycloalkyl or an optionally substituted 5-7-membered heterocyclyl; wherein Ring A ¹ and Ring B ¹ are fused together to form a bicyclic ring moiety that optionally can have a nitrogen at the bridgehead indicated with an asterisk; and when Ring A ¹ and Ring B ¹ are substituted, Ring A ¹ and Ring B ¹ can be independently substituted with 1 or more substituents independently selected from halogen, cyano, hydroxy, an unsubstituted C _1-4 alkyl, an unsubstituted C _1-4 hydroxyalkyl, amino, a mono-substituted amine and a di-substituted amine, Y ^1- 1 can be O (oxygen), S (sulfur), CH2, CF2 or NR ^6-1 ; R ^6-1 can be selected from hydrogen, an unsubstituted C1-4 alkyl, an optionally substituted monocyclic C3-6 cycloalkyl, C1-4 hydroxyalkyl, –C(=O)R ^7-1 and –S(=O) ₂ R ^8-1 , wherein when the C _3-6 monocyclic cycloalkyl is substituted, the C _{3- 6} monocyclic cycloalkyl can be substituted with 1 or 2 halogens; R ^7-1 can be selected from an unsubstituted C1-4 alkyl, an unsubstituted halo-C1-4 alkyl, an optionally substituted monocyclic C3- 6 cycloalkyl, an optionally substituted C6-10 aryl, an optionally substituted 5- to 10-membered heteroaryl, an optionally substituted 4- to 8-membered heterocyclyl and an optionally substituted C6-10 aryl(C1-4 alkyl); R ^8-1 can be selected from an unsubstituted C1-4 alkyl, an unsubstituted halo- C1-4 alkyl, an optionally substituted monocyclic C3-6 cycloalkyl, an optionally substituted C6-10 aryl, an optionally substituted 5- to 10-membered heteroaryl, an optionally substituted 4- to 8- membered heterocyclyl and an optionally substituted C6-10 aryl(C1-4 alkyl); wherein when R ^7-1 and R ^8-1 are substituted, then R ^7-1 and R ^8-1 can be independently substituted with 1 or more substituents selected from halogen, an unsubstituted C _1-4 alkyl and an unsubstituted C _1-4 haloalkyl; Ring C ¹ can be an optionally substituted phenyl or an optionally substituted monocyclic heteroaryl, and when Ring C ¹ is substituted, Ring C ¹ can be substituted with 1 or more substituents independently selected from halogen, an unsubstituted C1-4 alkyl and an unsubstituted C1-4 haloalkyl; Y ^2-1 can be an optionally substituted C _1-4 alkylene, and when Y ^2-1 is substituted, Y ^2-1 can be substituted with 1 or more substituents independently selected from halogen and an unsubstituted C1-4 alkyl; Y ^3-1 can be O (oxygen), S (sulfur), CH2 or CF2; and m1 can be 0, 1, 2 or 3. [0054] The phenyl ring of the indole of Formula (II) can be unsubstituted or substituted. In some embodiments, R ^1-1 , R ^2-1 and R ^3-1 can each be hydrogen. When the phenyl ring of the indole ring is substituted, the phenyl ring can be mono-, di- or tri-substituted. In some embodiments, R ^1-1 can be halogen (such as fluoro or chloro). In other embodiments, R ^1-1 can be an unsubstituted C _1-4 alkyl. Examples of unsubstituted C _1-4 alkyls include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl and tert-butyl. In still other embodiments, R ^1-1 can be an unsubstituted C1-4 haloalkyl, such as CF3 and CHF2. In some embodiments, R ^2-1 can be hydrogen. In other embodiments, R ^2-1 can be halogen, including those described herein. In still other embodiments, R ^2-1 can be an unsubstituted C1-4 alkyl, such as those described herein. In yet still other embodiments, R ^2-1 can be an unsubstituted C1-4 haloalkyl. In some embodiments, R ^3-1 can be hydrogen. In other embodiments, R ^3-1 can be halogen, such as F or Cl. In still other embodiments, R ^3-1 can be an unsubstituted C1-4 alkyl (for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl and tert-butyl). In yet still other embodiments, R ^3-1 can be an unsubstituted C1-4 haloalkyl. In some embodiments, R ^1-1 can be halogen, an unsubstituted C _1-4 alkyl or an unsubstituted C _1-4 haloalkyl; and R ^2-1 and R ^3-1 can be each hydrogen. In other embodiments, R ^1-1 and R ^3-1 can be independently halogen, an unsubstituted C _1-4 alkyl or an unsubstituted C _1-4 haloalkyl; and R ^2-1 can be hydrogen. [0055] The 5-membered ring of the indole can be unsubstituted or substituted. In some embodiments, R ^4-1 can be hydrogen. In other embodiments, R ^4-1 can be an unsubstituted C _1-4 alkyl. Suitable C1-4 alkyls are described herein and include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl and tert-butyl. In some embodiments, R ^4-1 can be an unsubstituted C3-6 monocyclic cycloalkyl. In other embodiments, R ^4-1 can be a substituted C _3-6 monocyclic cycloalkyl substituted with 1 or 2 halogens (for example, fluoro or chloro). Examples of C3-6 monocyclic cycloalkyls include cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. In still other embodiments, R ^4-1 can be an unsubstituted C _1-4 haloalkyl, such as CHF ₂ and CF ₃ . [0056] In other embodiments, Z ¹ can be CH ₂ ; and each ---- can be a single bond. In other embodiments, Z ¹ can be CH; and each ---- can be a double bond. In still other embodiments, Z ¹ can be NH; and each ---- can be a single bond. Examples of the bicyclic ring that includes Z ¹ . s, m1 can be 0, such that upper ring is unsubstituted. In other embodiments, m1 can be 1, wherein R ^5-1 can be halogen or an unsubstituted substituted C1-4 alkyl. In still other embodiments, m1 can be 2, wherein each R ^5-1 can be independently halogen or an unsubstituted substituted C _1-4 alkyl. In yet still other embodiments, m1 can be 3, wherein each R ^5-1 can be independently halogen or an unsubstituted substituted C _1-4 alkyl. Suitable halogens (including fluoro and chloro) and an optionally substituted C1-4 alkyls (optionally substituted versions of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl and tert-butyl). In some embodiments, each R ^5-1 can be independently an unsubstituted C _1-4 alkyl. [0058] In some embodiments, Y ^1-1 can be O (oxygen). In other embodiments, Y ^1-1 can be S (sulfur). In still other embodiments, Y ^1-1 can be CH ₂ . In yet still other embodiments, Y ^1-1 can be CF ₂ . In some embodiments, Y ^1-1 can be NR ^6-1 , wherein R ^6-1 can be hydrogen. In other embodiments, Y ^1-1 can be NR ^6-1 , wherein R ^6-1 can be an unsubstituted C1-4 alkyl. For example, R ^6-1 can be methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl. In still other embodiments, Y ^1-1 can be NR ^6-1 , wherein R ^6-1 can be an unsubstituted monocyclic C _3-6 cycloalkyl. In yet still other embodiments, Y ^1-1 can be NR ^6-1 , wherein R ^6-1 can be a substituted monocyclic C _3- 6 cycloalkyl substituted with 1 or 2 halogens. Suitable halogens include, but are not limited to, fluoro and chloro. In some embodiments, Y ^1-1 can be NR ^6-1 , wherein R ^6-1 can be C1-4 hydroxyalkyl. Exemplary C _1-4 hydroxyalkyls include the following: HOCH ₂ –, HOCH ₂ CH ₂ –, HOCH ₂ CH ₂ CH ₂ – , HOCH2CH2CH2CH2–, CH3CH2CH(OH)–, CH3CH(OH) CH2– and HOCH2CH(OH)–. In other embodiments, Y ^1-1 can be NR ^6-1 , wherein R ^6-1 can be –C(=O)R ^7-1 , wherein R ^7-1 can be selected from an unsubstituted C _1-4 alkyl, an unsubstituted halo-C _1-4 alkyl, an optionally substituted monocyclic C3-6 cycloalkyl, an optionally substituted C6-10 aryl, an optionally substituted 5- to 10- membered heteroaryl, an optionally substituted 4- to 8-membered heterocyclyl and an optionally substituted C _6-10 aryl(C _1-4 alkyl). In still other embodiments, Y ^1-1 can be NR ^6-1 , wherein R ^6-1 can be –S(=O) ₂ R ^8-1 , R ^8-1 can be selected from an unsubstituted C _1-4 alkyl, an unsubstituted halo-C _1-4 alkyl, an optionally substituted monocyclic C3-6 cycloalkyl, an optionally substituted C6-10 aryl, an optionally substituted 5- to 10-membered heteroaryl, an optionally substituted 4- to 8-membered heterocyclyl and an optionally substituted C _6-10 aryl(C _1-4 alkyl). When R ^7-1 and R ^8-1 are substituted, then R ^7-1 and R ^8-1 can be independently substituted with 1 or more substituents selected from halogen, an unsubstituted C1-4 alkyl and an unsubstituted C1-4 haloalkyl. For example, when R ^7-1 and R ^8-1 are substituted, R ^7-1 and/or R ^8-1 can be substituted 1, 2 or 3 times with a substituent selected from halogen (such as F or Cl), an unsubstituted C1-4 alkyl (for example, methyl, ethyl, n- propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl and tert-butyl) and an unsubstituted C1-4 haloalkyl (such as such as CF ₃ and CHF ₂ ) [0059] Examples of R ^7-1 and R ^8-1 groups include the following: methyl, ethyl, n- propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, –CF3, –CHF2, –CH2F, –CCl3, –CHCl2,

embodiments, Y ^2-1 can be a substituted C _1-4 alkylene, wherein when Y ^2-1 can be substituted, each substituent can be independently halogen or an unsubstituted C1-4 alkyl. Exemplary optionally substituted C1-4 alkylenes for Y ^2-1 include: –CH2–, –CH2CH2–, –CH2CH2CH2–, –CH ₂ CH ₂ CH ₂ CH ₂ –, –CH(CH ₃ )CH ₂ CH ₂ –, –CHFCH ₂ CH ₂ – and –CH ₂ CF ₂ CH ₂ –. [0061] In some embodiments, Y ^3-1 can be O (oxygen). In other embodiments, Y ^3-1 can be S (sulfur). In still other embodiments, Y ^3-1 can be CH2. In yet still other embodiments, Y ^3-1 can be CF2. [0062] In some embodiments, Ring A ¹ can be an unsubstituted 5-membered heteroaryl. In other embodiments, Ring A ¹ can be Ring A ¹ can be a substituted 5-membered heteroaryl. In some embodiments, Ring B ¹ can be a unsubstituted 3-7 membered cycloalkyl. In other embodiments, Ring B ¹ can be a substituted 3-7 membered cycloalkyl. In still other embodiments, Ring B ¹ can be an unsubstituted 5-7-membered heterocyclyl. In yet still other embodiments, Ring B ¹ can be a substituted 5-7-membered heterocyclyl. As provided herein, Ring A ¹ and Ring B ¹ can be fused together to form a bicyclic ring moiety that optionally has a nitrogen at the bridgehead indicated with an asterisk ). In some embodiments, Ring A ¹ and Ring B ¹ can be fused together to form a bicyclic ring moiety that has a nitrogen at the bridgehead indicated with an asterisk. In other embodiments, Ring A ¹ and Ring B ¹ can be fused together to form a bicyclic ring moiety that has a carbon at the bridgehead indicated with an asterisk. [0063] As provided herein Ring A ¹ and/or Ring B ¹ is substituted. When Ring A ¹ and/or Ring B ¹ are substituted, 1 or more substituents (such as 1, 2 or 3 substituents) can be present. In some embodiments, Ring A ¹ and/or Ring B ¹ can be mono-substituted. In other embodiments, Ring A ¹ and/or Ring B ¹ can be di-substituted. Examples of possible substituents that can be present on Ring A ¹ and/or B ¹ include halogen (such as fluoro and chloro), cyano, hydroxy, an unsubstituted C _1-4 alkyl (for example, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl and tert- butyl), an unsubstituted C1-4 hydroxyalkyl (such as –CH2OH, –CH2CH2OH, –CH2CH2CH2OH, – CH2CH2CH2CH2OH, –CH2CH(OH)CH3, –CH2CH2C(OH)2CH3 and –CH2CH(OH)CH(OH)CH3), amino, a mono-substituted amine (such as –NH(C _1-4 alkyl) and –NH(unsubstituted or substituted benzyl)) and a di-substituted amine (for example, as –N(C1-4 alkyl)2 and –N(C1-4 alkyl)(unsubstituted or substituted benzyl)). [0064] Examples o where the bridgehead indicated with an asterisk is a carbon includes: . Exemplary where the bridgehead indicated with an asterisk is a nitrogen includes: [0065] In some embodiments can be selected fro , embodiments, Ring C ¹ can be a substituted phenyl. In still other embodiments, Ring C ¹ can be an unsubstituted monocyclic heteroaryl. In yet still other embodiments, Ring C ¹ can be a substituted monocyclic heteroaryl. The monocyclic heteroaryl can be an optionally substituted monocyclic, 5- to 6-membered, nitrogen-containing heteroaryl. When Ring C ¹ is substituted, Ring C ¹ can be mono-substituted or di-substituted with a substituent(s) independently selected from halogen, an unsubstituted C1-4 alkyl and an unsubstituted C1-4 haloalkyl. As examples, Ring C ¹ can be mono- substituted or di-substituted with fluoro, chloro, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso- butyl, sec-butyl, tert-butyl, –CF ₃ , –CHF ₂ , –CH ₂ F, –CCl ₃ , –CHCl ₂ and –CH ₂ Cl. [0067] Suitable examples of Ring C ¹ include an unsubstituted or a substituted pyrazole, an unsubstituted or a substituted thiazole, an unsubstituted or a substituted oxazole, an unsubstituted or a substituted 1,3,4-oxadiazole, an unsubstituted or a substituted 1,3,4-thiadiazole and an unsubstituted or a substituted pyridine, where each of the aforementioned can be substituted as described in the previous paragraph. In some embodiments, Ring C ¹ can be selected from . One skilled in the art realizes that the connectivity of these foregoing examples of Ring C ¹ can connect in two ways. For example, when Ring C ¹ the compound of Formula (II) can be and unds of Formula (II), and pharmaceutically acceptable salts thereof, include the following:

pharmaceutically acceptable salt of any of the foregoing. [0069] Additional examples of compounds of Formula (II), and pharmaceutically acceptable salts thereof, include the following:

pharmaceutically acceptable salt of any of the foregoing. [0070] Further examples of compounds of Formula (II), and pharmaceutically acceptable salts thereof, include the following:

pharmaceutically acceptable salt of any of the foregoing.

[0071] Other examples of compounds of Formula (II), and pharmaceutically acceptable salts thereof, include the following: , , , ,

[0072] In some embodiments, R ^6-1 cannot be methyl. In some embodiments, R ^7-1 cannot be methyl. In some embodiments, R ^1-1 cannot be chloro. In some embodiments, R ^2-1 cannot be hydrogen. In some embodiments, R ^2-1 cannot be fluoro. In some embodiments, R ^1-1 cannot be chloro when R ^6-1 is methyl. In some embodiments, when R ^2-1 is hydrogen; then R ^1-1 cannot be chloro. In other embodiments, when R ^2-1 is fluoro; then R ^1-1 cannot be chloro. In some embodiments, when R ^2-1 is hydrogen; and R ^6-1 is methyl; then R ^1-1 cannot be chloro. In other embodiments, when R ^2-1 is fluoro; and R ^6-1 is methyl; then R ^1-1 cannot be chloro. [0073] In some embodiments, a compound of Formula (II), or a pharmaceutically acceptable salt thereof, cannot a compound disclosed in WO 2018/178226 that would be encompassed by a compound of Formula (II), or a pharmaceutically acceptable salt thereof. In some embodiments, a compound of Formula (II), or a pharmaceutically acceptable salt thereof, cannot a compound disclosed in WO 2017/181625 that would be encompassed by a compound of Formula (II), or a pharmaceutically acceptable salt thereof. In some embodiments, a compound of Formula (II), or a pharmaceutically acceptable salt thereof, cannot a compound disclosed in WO 2020/103864 that would be encompassed by a compound of Formula (II), or a pharmaceutically acceptable salt thereof. In some embodiments, a compound of Formula (II), or a pharmaceutically acceptable salt thereof, cannot a compound disclosed in WO 2020/151738 that would be encompassed by a compound of Formula (II), or a pharmaceutically acceptable salt thereof. In some embodiments, a compound of Formula (II), or a pharmaceutically acceptable salt thereof, cannot a compound disclosed in WO 2020/185606 that would be encompassed by a compound of Formula (II), or a pharmaceutically acceptable salt thereof. In some embodiments, a compound of Formula (II), or a pharmaceutically acceptable salt thereof, cannot a compound disclosed in PCT Application No. PCT/US2020/045255 that would be encompassed by a compound of Formula (II), or a pharmaceutically acceptable salt thereof. Synthesis [0074] Compounds of the Formula (I) and Formula (II), along with pharmaceutically acceptable salts of any of the foregoing, can be made in various ways by those skilled using known techniques as guided by the detailed teachings provided herein. For example, in an embodiment, compounds of the Formulae (I) and (II) are prepared in accordance with General Scheme 1 as shown herein. General Scheme 1 any of the foregoing, can be prepared according to the preparation shown in General Scheme 1. Compound (A) can undergo a Mitsunobu reaction and close the ring to form the macrocyclic Compound (B). In General Scheme 1, P represents a suitable protecting group. Removal of the protecting group via a hydrolysis reaction provides a compound of Formula (I) and/or a compound of Formula (II), including pharmaceutically acceptable salts of any of the foregoing. Pharmaceutical Compositions [0076] Some embodiments described herein relate to a pharmaceutical composition, that can include an effective amount of one or more compounds described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) and a pharmaceutically acceptable carrier, diluent, excipient or combination thereof. [0077] The term “pharmaceutical composition” refers to a mixture of one or more compounds and/or salts disclosed herein with other chemical components, such as diluents or carriers. The pharmaceutical composition facilitates administration of the compound to an organism. Pharmaceutical compositions can also be obtained by reacting compounds with inorganic or organic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, and salicylic acid. Pharmaceutical compositions will generally be tailored to the specific intended route of administration. [0078] The term “physiologically acceptable” defines a carrier, diluent or excipient that does not abrogate the biological activity and properties of the compound nor cause appreciable damage or injury to an animal to which delivery of the composition is intended. [0079] As used herein, a “carrier” refers to a compound that facilitates the incorporation of a compound into cells or tissues. For example, without limitation, dimethyl sulfoxide (DMSO) is a commonly utilized carrier that facilitates the uptake of many organic compounds into cells or tissues of a subject. [0080] As used herein, a “diluent” refers to an ingredient in a pharmaceutical composition that lacks appreciable pharmacological activity but may be pharmaceutically necessary or desirable. For example, a diluent may be used to increase the bulk of a potent drug whose mass is too small for manufacture and/or administration. It may also be a liquid for the dissolution of a drug to be administered by injection, ingestion or inhalation. A common form of diluent in the art is a buffered aqueous solution such as, without limitation, phosphate buffered saline that mimics the pH and isotonicity of human blood. [0081] As used herein, an “excipient” refers to an essentially inert substance that is added to a pharmaceutical composition to provide, without limitation, bulk, consistency, stability, binding ability, lubrication, disintegrating ability etc., to the composition. For example, stabilizers such as anti-oxidants and metal-chelating agents are excipients. In an embodiment, the pharmaceutical composition comprises an anti-oxidant and/or a metal-chelating agent. A “diluent” is a type of excipient. [0082] The pharmaceutical compositions described herein can be administered to a human patient per se, or in pharmaceutical compositions where they are mixed with other active ingredients, as in combination therapy, or carriers, diluents, excipients or combinations thereof. Proper formulation is dependent upon the route of administration chosen. Techniques for formulation and administration of the compounds described herein are known to those skilled in the art. [0083] The pharmaceutical compositions disclosed herein may be manufactured in a manner that is itself known, e.g., by means of conventional mixing, dissolving, granulating, dragee-making, levigating, emulsifying, encapsulating, entrapping or tableting processes. Additionally, the active ingredients are contained in an amount effective to achieve its intended purpose. Many of the compounds used in the pharmaceutical combinations disclosed herein may be provided as salts with pharmaceutically compatible counterions. [0084] Multiple techniques of administering a compound, salt and/or composition exist in the art including, but not limited to, oral, rectal, pulmonary, topical, aerosol, injection, infusion and parenteral delivery, including intramuscular, subcutaneous, intravenous, intramedullary injections, intrathecal, direct intraventricular, intraperitoneal, intranasal and intraocular injections. In some embodiments, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing, can be administered orally. [0085] One may also administer the compound, salt and/or composition in a local rather than systemic manner, for example, via injection or implantation of the compound directly into the affected area, often in a depot or sustained release formulation. Furthermore, one may administer the compound in a targeted drug delivery system, for example, in a liposome coated with a tissue-specific antibody. The liposomes will be targeted to and taken up selectively by the organ. For example, intranasal or pulmonary delivery to target a respiratory disease or condition may be desirable. [0086] The compositions may, if desired, be presented in a pack or dispenser device which may contain one or more unit dosage forms containing the active ingredient. The pack may for example comprise metal or plastic foil, such as a blister pack. The pack or dispenser device may be accompanied by instructions for administration. The pack or dispenser may also be accompanied with a notice associated with the container in form prescribed by a governmental agency regulating the manufacture, use, or sale of pharmaceuticals, which notice is reflective of approval by the agency of the form of the drug for human or veterinary administration. Such notice, for example, may be the labeling approved by the U.S. Food and Drug Administration for prescription drugs, or the approved product insert. Compositions that can include a compound and/or salt described herein formulated in a compatible pharmaceutical carrier may also be prepared, placed in an appropriate container, and labeled for treatment of an indicated condition. Uses and Methods of Treatment [0087] Some embodiments described herein relate to a method for ameliorating and/or treating a cancer described herein that can include administering an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) or a pharmaceutical composition that includes an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) to a subject having a cancer described herein. Other embodiments described herein relate to the use of an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) or a pharmaceutical composition that includes an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) in the manufacture of a medicament for ameliorating and/or treating a cancer described herein. Still other embodiments described herein relate to an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) or a pharmaceutical composition that includes an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) for ameliorating and/or treating a cancer described herein. [0088] Some embodiments described herein relate to a method for inhibiting replication of a malignant growth or a tumor that can include contacting the growth or the tumor with an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) or a pharmaceutical composition that includes an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing), wherein the malignant growth or tumor is due to a cancer described herein. Other embodiments described herein relate to the use of an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) or a pharmaceutical composition that includes an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) in the manufacture of a medicament for inhibiting replication of a malignant growth or a tumor, wherein the malignant growth or tumor is due to a cancer described herein. Still other embodiments described herein relate to an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) or a pharmaceutical composition that includes an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) for inhibiting replication of a malignant growth or a tumor, wherein the malignant growth or tumor is due to a cancer described herein. [0089] Some embodiments described herein relate to a method for ameliorating or treating a cancer described herein that can include contacting a malignant growth or a tumor with an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) or a pharmaceutical composition that includes an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) to a subject having a cancer described herein. Other embodiments described herein relate to the use of an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) or a pharmaceutical composition that includes an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) in the manufacture of a medicament for ameliorating or treating a cancer that can include contacting a malignant growth or a tumor, wherein the malignant growth or tumor is due to a cancer described herein. Still other embodiments described herein relate to an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) or a pharmaceutical composition that includes an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) for ameliorating or treating a cancer that can include contacting a malignant growth or a tumor, wherein the malignant growth or tumor is due to a cancer described herein. [0090] Some embodiments described herein relate to a method for inhibiting the activity of Mcl-1 that can include providing an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) or a pharmaceutical composition that includes an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) to a cancer cell from a cancer described herein. Other embodiments described herein relate to the use of an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) or a pharmaceutical composition that includes an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) in the manufacture of a medicament for inhibiting the activity of Mcl-1. Still other embodiments described herein relate to an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) or a pharmaceutical composition that includes an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) for inhibiting the activity of Mcl-1. Some embodiments described herein relate to a method for inhibiting the activity of Mcl-1 that can include providing an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) or a pharmaceutical composition that includes an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) to a cancer cell from a cancer described herein. Other embodiments described herein relate to a method for inhibiting the activity of Mcl- 1 that can include contacting a cancer cell from a cancer described herein with an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) or a pharmaceutical composition that includes an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing), and thereby inhibiting the activity of Mcl-1. [0091] Some embodiments described herein relate to a method for ameliorating or treating a cancer described herein that can include inhibiting the activity of Mcl-1 using an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) or a pharmaceutical composition that includes an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing). Other embodiments described herein relate to the use of an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) or a pharmaceutical composition that includes an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) in the manufacture of a medicament for ameliorating or treating a cancer described herein by inhibiting the activity of Mcl-1. Still other embodiments described herein relate to an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) or a pharmaceutical composition that includes an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) for ameliorating or treating a cancer described herein by inhibiting the activity of Mcl-1. Some embodiments described herein relate to a method for ameliorating or treating a cancer described herein that can include contacting a cancer cell with an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) or a pharmaceutical composition that includes an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing), wherein the compound inhibits the activity of Mcl-1. [0092] Some embodiments disclosed herein relate to a method for inhibiting the activity of Mcl-1 that can include providing an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) or a pharmaceutical composition that includes an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) to a subject having a cancer described herein or a cancer cell from a cancer described herein. Other embodiments disclosed herein relate to the use of an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) or a pharmaceutical composition that includes an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) in the manufacture of a medicament for inhibiting the activity of Mcl-1. Still other embodiments disclosed herein relate to a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) or a pharmaceutical composition that includes an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) for inhibiting the activity of Mcl-1. [0093] Examples of suitable cancers include, but are not limited to: hematological malignancies (such as acute myeloid leukemia, multiple myeloma, mantle cell lymphoma, chronic lymphocytic leukemia, diffuse large B cell lymphoma, Burkitt’s lymphoma, follicular lymphoma) and solid tumors, for example, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), breast cancer, neuroblastoma, prostate cancer, melanoma, pancreatic cancer, uterine, endometrial, colon, esophagus and liver cancers, osteosarcoma, Hodgkin lymphoma, mesothelioma, meningioma, glioma and tumors of upper aerodigestive, ovarian, thyroid, stomach and urinary tract. In some embodiments, the cancer can be selected from a brain cancer, a cervicocerebral cancer, an esophageal cancer, a thyroid cancer, a small cell cancer, a non-small cell cancer, a breast cancer, a lung cancer , a stomach cancer, a gallbladder/bile duct cancer, a liver cancer, a pancreatic cancer, a colon cancer, a rectal cancer, an ovarian cancer, a choriocarcinoma, an uterus body cancer, an uterocervical cancer, a renal pelvis/ureter cancer, a bladder cancer, a prostate cancer, a penis cancer, a testicular cancer, a fetal cancer, Wilms' cancer, a skin cancer, malignant melanoma, a neuroblastoma, an osteosarcoma, an Ewing's tumor, a soft part sarcoma, an acute leukemia, a chronic lymphatic leukemia, a chronic myelocytic leukemia, polycythemia vera, a malignant lymphoma, multiple myeloma, a Hodgkin's lymphoma, and a non-Hodgkin’s lymphoma. [0094] As described herein, a cancer can become resistant to one or more anti-cancer agents. In some embodiments, a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) or a pharmaceutical composition that includes an effective amount of a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) can be used to treat and/or ameliorate a cancer that has become resistant to one or more anti-cancer agents (such as one or more Mcl-1 inhibitors). Examples of anti-cancer agents that a subject may have developed resistance to include, but are not limited to, Mcl-1 inhibitors (such as AT101, gambogic acid, TW-37, AZD5991, Sabutoclax (BI-97C1), Maritoclax, UMI-77, A-1210477, ^{S63845, MIK665/S64315, (-)BI97D6 and/or AMG176). In some embodiments, the cancer that} has become resistant to one or more anti-cancer agents can be a cancer described herein. [0095] Several known Mcl-1 inhibitors can cause one or more undesirable side effects in the subject being treated. Examples of undesirable side effects include, but are not limited to, thrombocytopenia, neutropenia, anemia, diarrhea, vomiting, nausea, abdominal pain, and constipation ^. In some embodiments, a compound described herein (for example, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing) can decrease the number and/or severity of one or more side effects associated with a known Mcl-1 inhibitor. In some embodiments, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing, can result in a severity of a side effect (such as one of those described herein) that is 25% less than compared to the severity of the same side effect experienced by a subject receiving a known Mcl-1 inhibitor (such as AT101, gambogic acid, TW-37, AZD5991, Sabutoclax (BI-97C1), Maritoclax, UMI-77, A-1210477, S63845, MIK665/S64315, (-)BI97D6 and/or AMG176). In some embodiments, a compound of Formula (I), or a pharmaceutically acceptable salt thereof, results in a number of side effects that is 25% less than compared to the number of side effects experienced by a subject receiving a known Mcl-1. In some embodiments, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing, results in a severity of a side effect (such as one of those described herein) that is less in the range of about 10% to about 30% compared to the severity of the same side effect experienced by a subject receiving a known Mcl- 1. In some embodiments, a compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing, results in a number of side effects that is in the range of about 10% to about 30% less than compared to the number of side effects experienced by a subject receiving a known Mcl-1. [0096] The one or more compounds of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing, that can be used to treat, ameliorate and/or inhibit the growth of a cancer wherein inhibiting the activity of Mcl-1 is beneficial is provided in any of the embodiments described in paragraphs [0035]-[0073], under the headings titled “Compounds – Formula (I)” and “Compounds – Formula (II)” [0097] As used herein, a “subject” refers to an animal that is the object of treatment, observation or experiment. “Animal” includes cold- and warm-blooded vertebrates and invertebrates such as fish, shellfish, reptiles and, in particular, mammals. “Mammal” includes, without limitation, mice, rats, rabbits, guinea pigs, dogs, cats, sheep, goats, cows, horses, primates, such as monkeys, chimpanzees, and apes, and, in particular, humans. In some embodiments, the subject can be human. In some embodiments, the subject can be a child and/or an infant, for example, a child or infant with a fever. In other embodiments, the subject can be an adult. [0098] As used herein, the terms “treat,” “treating,” “treatment,” “therapeutic,” and “therapy” do not necessarily mean total cure or abolition of the disease or condition. Any alleviation of any undesired signs or symptoms of the disease or condition, to any extent can be considered treatment and/or therapy. Furthermore, treatment may include acts that may worsen the subject’s overall feeling of well-being or appearance. [0099] The terms “therapeutically effective amount” and “effective amount” are used to indicate an amount of an active compound, or pharmaceutical agent, that elicits the biological or medicinal response indicated. For example, a therapeutically effective amount of compound, salt or composition can be the amount needed to prevent, alleviate or ameliorate symptoms of the disease or condition, or prolong the survival of the subject being treated. This response may occur in a tissue, system, animal or human and includes alleviation of the signs or symptoms of the disease or condition being treated. Determination of an effective amount is well within the capability of those skilled in the art, in view of the disclosure provided herein. The therapeutically effective amount of the compounds disclosed herein required as a dose will depend on the route of administration, the type of animal, including human, being treated and the physical characteristics of the specific animal under consideration. The dose can be tailored to achieve a desired effect, but will depend on such factors as weight, diet, concurrent medication and other factors which those skilled in the medical arts will recognize. [0100] For example, an effective amount of a compound, or radiation, is the amount that results in: (a) the reduction, alleviation or disappearance of one or more symptoms caused by the cancer, (b) the reduction of tumor size, (c) the elimination of the tumor, and/or (d) long-term disease stabilization (growth arrest) of the tumor. In the treatment of lung cancer (such as non- small cell lung cancer) a therapeutically effective amount is that amount that alleviates or eliminates cough, shortness of breath and/or pain. As another example, an effective amount, or a therapeutically effective amount of a Mcl-1 inhibitor is the amount which results in the reduction in Mcl-1 activity and/or phosphorylation (such as phosphorylation of CDC2). The reduction in Mcl-1 activity is known to those skilled in the art and can be determined by the analysis of Mcl-1 intrinsic kinase activity and downstream substrate phosphorylation. [0101] The amount of the compound of Formula (I) and/or a compound of Formula (II), or a pharmaceutically acceptable salt of any of the foregoing, required for use in treatment will vary not only with the particular compound or salt selected but also with the route of administration, the nature and/or symptoms of the disease or condition being treated and the age and condition of the patient and will be ultimately at the discretion of the attendant physician or clinician. In cases of administration of a pharmaceutically acceptable salt, dosages may be calculated as the free base. As will be understood by those of skill in the art, in certain situations it may be necessary to administer the compounds disclosed herein in amounts that exceed, or even far exceed, the dosage ranges described herein in order to effectively and aggressively treat particularly aggressive diseases or conditions. [0102] In general, however, a suitable dose will often be in the range of from about 0.05 mg/kg to about 10 mg/kg. For example, a suitable dose may be in the range from about 0.10 mg/kg to about 7.5 mg/kg of body weight per day, such as about 0.15 mg/kg to about 5.0 mg/kg of body weight of the recipient per day, about 0.2 mg/kg to 4.0 mg/kg of body weight of the recipient per day, or any amount in between. The compound may be administered in unit dosage form; for example, containing 1 to 500 mg, 10 to 100 mg, 5 to 50 mg or any amount in between, of active ingredient per unit dosage form. [0103] The desired dose may conveniently be presented in a single dose or as divided doses administered at appropriate intervals, for example, as two, three, four or more sub-doses per day. The sub-dose itself may be further divided, e.g., into a number of discrete loosely spaced administrations. [0104] As will be readily apparent to one skilled in the art, the useful in vivo dosage to be administered and the particular mode of administration will vary depending upon the age, weight, the severity of the affliction, the mammalian species treated, the particular compounds employed and the specific use for which these compounds are employed. The determination of effective dosage levels, that is the dosage levels necessary to achieve the desired result, can be accomplished by one skilled in the art using routine methods, for example, human clinical trials, in vivo studies and in vitro studies. For example, useful dosages of a compound of Formula (I) and/or a compound of Formula (II), or pharmaceutically acceptable salts of any of the foregoing, can be determined by comparing their in vitro activity, and in vivo activity in animal models. Such comparison can be done by comparison against an established drug, such as cisplatin and/or gemcitabine) [0105] Dosage amount and interval may be adjusted individually to provide plasma levels of the active moiety which are sufficient to maintain the modulating effects, or minimal effective concentration (MEC). The MEC will vary for each compound but can be estimated from in vivo and/or in vitro data. Dosages necessary to achieve the MEC will depend on individual characteristics and route of administration. However, HPLC assays or bioassays can be used to determine plasma concentrations. Dosage intervals can also be determined using MEC value. Compositions should be administered using a regimen which maintains plasma levels above the MEC for 10-90% of the time, preferably between 30-90% and most preferably between 50-90%. In cases of local administration or selective uptake, the effective local concentration of the drug may not be related to plasma concentration. [0106] It should be noted that the attending physician would know how to and when to terminate, interrupt or adjust administration due to toxicity or organ dysfunctions. Conversely, the attending physician would also know to adjust treatment to higher levels if the clinical response were not adequate (precluding toxicity). The magnitude of an administrated dose in the management of the disorder of interest will vary with the severity of the disease or condition to be treated and to the route of administration. The severity of the disease or condition may, for example, be evaluated, in part, by standard prognostic evaluation methods. Further, the dose and perhaps dose frequency, will also vary according to the age, body weight and response of the individual patient. A program comparable to that discussed above may be used in veterinary medicine. [0107] Compounds, salts and compositions disclosed herein can be evaluated for efficacy and toxicity using known methods. For example, the toxicology of a particular compound, or of a subset of the compounds, sharing certain chemical moieties, may be established by determining in vitro toxicity towards a cell line, such as a mammalian, and preferably human, cell line. The results of such studies are often predictive of toxicity in animals, such as mammals, or more specifically, humans. Alternatively, the toxicity of particular compounds in an animal model, such as mice, rats, rabbits, dogs or monkeys, may be determined using known methods. The efficacy of a particular compound may be established using several recognized methods, such as in vitro methods, animal models, or human clinical trials. When selecting a model to determine efficacy, the skilled artisan can be guided by the state of the art to choose an appropriate model, dose, route of administration and/or regime. EXAMPLES [0108] Additional embodiments are disclosed in further detail in the following examples, which are not in any way intended to limit the scope of the claims. Intermediate 1 (1-Ethyl-3-methyl-1H-pyrazol-5-yl)methanol [0109] To a stirred solution of 1-ethyl-3-methyl-1H-pyrazole-5-carboxylic acid (35.0 g, 227 mmol) in THF (350 mL) was added 2.4M LiAlH4 in THF (104 mL, 249 mmol) at 0 °C. The mixture was stirred at room temperature (rt) for 2 h. Upon completion by LCMS, the reaction was quenched with cold sat. Na ₂ SO ₄ (200 mL) at 0 °C. The mixture was filtered through a Celite pad and washed with EtOAc (2 x 250 mL). The filtrate was washed with brine (500 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to afford Intermediate 1 (30 g, 94%) as an oil. MS (ESI) 141.1 [M+H] ⁺ . Intermediate 2 (4-Bromo-1-ethyl-3-methyl-1H-pyrazol-5-yl)methanol [0110] To a stirred solution te 1 (30.0 g, 214 mmol) in DCM (300 mL) was added NBS (40.0 g, 225 mmol) portion-wise over 30 min. at 0 °C. The ice bath was removed, and the mixture was stirred for 1 h at rt. Upon completion by LCMS, the reaction was quenched with water (500 mL) and diluted with DCM (500 mL). The layers were separated. The organic layer was washed with brine (500 mL), dried (Na ₂ SO ₄ ) _, filtered and concentrated. The crude mixture was triturated with a mixture of n-pentane (300 mL) and diethyl ether (100 mL). The product was filtered and dried under reduced pressure to afford Intermediate 2 (30 g, 64%). MS (ESI) 219.2 [M+H] ⁺ . Intermediate 3 4-Bromo-1-ethyl-5-(((4-methoxybenzyl)oxy)methyl)-3-methyl-1H -pyrazole [0111] To a stirred solutio 2 (30.0 g, 137 mmol) in DMF (300 mL) was added 60 % NaH (8.20 g, 342 mmol) at 0 °C. The ice bath was removed, and the mixture was stirred at rt for 30 min. 1-(Chloromethyl)-4-methoxybenzene (32.0 g, 205.1 mmol) and KI (4.40 g, 26.5 mmol) was added, and the mixture was stirred at rt for 16 h. Upon completion, the reaction was quenched with ice, diluted with water (700 mL) and extracted with EtOAc (3 x 500 mL). The combined organic layers were washed with water (2 x 500 mL) and brine (500 mL). The organic layer was dried (Na2SO4), filtered and concentrated. The crude material was purified by flash chromatography (SiO2, 20% EtOAc:Petroleum Ether (PE)) to afford Intermediate 3 (28 g, 60%) as an oil. MS (LCMS) 339.2 [M+H] ⁺ . Intermediate 4 1-Ethyl-5-(((4-methoxybenzyl)oxy)methyl)-3-methyl-4-(4,4,5,5 -tetramethyl-1,3,2-dioxaborolan- 2-yl)-1H-pyrazole [0112] To a stirred solutio 3 (28.0 g, 82.8 mmol) in THF (300 mL) was added 1.6 M n-BuLi in hexanes (38.0 mL, 99.4 mmol) at -78 °C. The mixture was stirred for 1 h at -78 °C. 2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (44.28 g, 238.1 mmol) was added at -78 °C, and the mixture was stirred at -78 ^o C for 1 h. Upon completion, the reaction was quenched with EtOAc (50 mL) and allowed to warm to rt. The solvent was removed, and the crude was diluted with EtOAc (300 mL). The mixture was filtered through a Celite pad which was washed with EtOAc (2 x 100 mL). The filtrate was evaporated, and the crude product was triturated with n-pentane. The product was collected by filtration and dried under vacuum to afford Intermediate 4 (17 g, 53%). MS (ESI) 387.0 [M+H] ⁺ . Intermediate 5 Methyl 3-(3-acetoxypropyl)-7-bromo-6-chloro-1-methyl-1H-indole-2-ca rboxylate [0113] Intermediate 5 lowing the procedure as described in WO 2020/185606 A1. Intermediate 6 Methyl 3-(3-acetoxypropyl)-6-chloro-7-(1-ethyl-5-(((4-methoxybenzyl )oxy)methyl)-3-methyl- 1H-pyrazol-4-yl)-1-methyl-1H-indole-2-carboxylate [0114] To a stirred solut 17.0 g, 44.0 mmol) in 1,4-dioxane (170 mL) was added Intermediate 5 (12.2 g, 30.3 mmol) and Cs2CO3 (28.68 g, 87.98 mmol). The solution was degassed with Ar for 10 mins. Tetrakis(triphenylphosphine)palladium (5.00 g, 4.33 mmol) was added, and the mixture was degassed for 10 min. The mixture was heated at 100 °C for 16 h. Upon completion, the mixture was passed through Celite, and the pad was washed with EtOAc (2 x 100 mL). The filtrate was washed with water (2 x 100 mL) and brine (1 x 100 mL), dried (Na2SO4), filtered and concentrated. The residue was purified by flash chromatography (SiO2, 35-50% EtOAc:PE) to afford Intermediate 6 (10 g, 34%) as an oil. MS (ESI) 582.5 [M+H] ⁺ . Intermediate 7 Methyl 3-(3-acetoxypropyl)-6-chloro-7-(1-ethyl-5-(hydroxymethyl)-3- methyl-1H-pyrazol-4-yl)- 1-methyl-1H-indole-2-carboxylate [0115] To a stirred solu (10.0 g, 17.6 mmol) in DCM (100 mL) was added TFA (13.14 mL, 19.59 mmol) at 0 ^o C. The ice bath was removed, and the reaction was stirred at rt for 2 h. Upon completion, the reaction was quenched with sat. NaHCO3 (100 mL) at 0 ^o C. The product was collected by filtration and washed with water (100 mL). The product was dissolved in DCM (500 mL), dried (Na ₂ SO ₄ ), filtered and the solvent evaporated. The residue was purified by flash chromatography (SiO ₂ , 5% MeOH:DCM) to afford Intermediate 7 (6 g, 75%). MS (ESI) 462.3 [M+H] ⁺ . Intermediate 8 Methyl 3-(3-acetoxypropyl)-6-chloro-7-(5-(chloromethyl)-1-ethyl-3-m ethyl-1H-pyrazol-4-yl)-1- methyl-1H-indole-2-carboxylate [0116] To a stirred solu (3.00 g, 6.51 mmol) in DCM (30 mL) under argon was added SOCl2 (0.56 mL, 7.8 mmol) at 0 °C. The ice bath was removed, and the reaction was stirred at rt for 30 min. The solvent was evaporated, and the reaction was quenched with sat. NaHCO3 (50 mL). The mixture was extracted with DCM (2 x 50 mL). The combined organic layers were washed with brine (1 x 75 mL), dried (Na2SO4), filtered and evaporated to afford Intermediate 8 (3 g) as an oil. MS (ESI) 480.3 [M+H] ⁺ . Intermediate 9 Methyl 3-(3-acetoxypropyl)-6-chloro-7-(1-ethyl-5-(iodomethyl)-3-met hyl-1H-pyrazol-4-yl)-1- methyl-1H-indole-2-carboxylate [0117] To a stirred solu (3.00 g, 6.25 mmol) in dry MeCN (30 mL) was added NaI (1.60 g, 10.7 mmol) at rt. The mixture was heated to 80 ^o C for 3 h. Upon completion, the solvent was evaporated, and the mixture was diluted with water (50 mL). The mixture was extracted with EtOAc (2 x 50 mL). The combined organic layers were dried (Na ₂ SO ₄ ), filtered and evaporated to afford Intermediate 9 (3 g). MS (LCMS) 572.3 [M+H] ⁺ . Intermediate 10 Ethyl 5-(chloromethyl)-4-methylthiazole-2-carboxylate [0118] To a stirred so 5-(hydroxymethyl)-4-methylthiazole-2- carboxylate (19 g, 94.5 mmol) in DCM (190 mL) was added SOCl2 (8.4 mL, 113.4 mmol) dropwise at 0 °C. The mixture was stirred at rt for 2 h. Progress of the reaction was monitored by TLC. After completion, the reaction was quenched with sat. aq. sodium bicarbonate solution (100 mL) and extracted with EtOAc (2 x 200 mL). The combined organic layers were washed with brine, dried (Na ₂ SO ₄ ), filtered and evaporated to dryness to provide Intermediate 10 (18.5 g, 89%) as a light-yellow sticky oil. The crude compound was used for next step without purification. MS (ESI) 220.0 [M+H] ⁺ . Intermediate 11 Ethyl 5-((acetylthio)methyl)-4-methylthiazole-2-carboxylate [0119] To a stirred solutio 10 (18.5 g, 84.4 mmol) in ACN (180 mL) was added potassium ethanethioate (19.2 g, 168.9 mmol) and KI (14.0 g, 84.4 mmol) at 0 °C. The mixture was stirred at rt for 16 h. Progress of the reaction was monitored by TLC and LCMS. After completion, the reaction was quenched with brine (100 mL) and extracted with EtOAc (2 x 100 mL). The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated. The crude material was purified by flash chromatography (SiO2, 10% EtOAc:PE) to afford Intermediate 11 (16.0 g, 62%) as a light-yellow sticky oil. MS (ESI) 260.5 [M+H] ⁺ . Intermediate 12 Ethyl 5-(((8-((4-methoxybenzyl)oxy)quinolin-6-yl)thio)methyl)-4-me thylthiazole-2-carboxylate [0120] To a stirred s 16.0 g, 61.7 mmol) and 6-bromo-8- ((4-methoxybenzyl)oxy)quinoline (WO 2018/178226 A1) (27.8 g, 61.7 mmol) in 1,4 Dioxane (160 mL) was added potassium carbonate (21.2 g, 154.4 mmol), Pd ₂ dba ₃ (5.6 g, 6.1 mmol) and Xphos (5.8 g, 12.3 mmol). The mixture was degassed using nitrogen for 10 min and heated at 100 °C for 16 h. Progress of the reaction was monitored by TLC and LCMS. After completion, the mixture was cooled to rt and then diluted with water (100 mL). The mixture was extracted with EtOAc (2 x 100 mL). The combined organic layers were washed with brine, dried (Na ₂ SO ₄ ), filtered and evaporated. The crude material was purified by flash chromatography (SiO2, 0-50% EtOAc:PE) to afford Intermediate 12 (15 g. 50%). MS (ESI) 481.3 [M+H] ⁺ . Intermediate 13 (5-(((8-((4-methoxybenzyl)oxy)quinolin-6-yl)thio)methyl)-4-m ethylthiazol-2-yl)methanol [0121] To a stirred solu 0 g, 27.3 mmol) in EtOH:THF (1:1, 120 mL) was added NaBH4 (8.2 g, 219.1 mmol) portion-wise at 0 ^o C. The mixture was stirred at rt for 16 h. Progress of the reaction was monitored by TLC. After completion, the reaction was quenched with ice cold water (100 mL) and then extracted with EtOAc (2 x 80 mL). The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated. The crude material was purified by flash chromatography (SiO ₂ , 0-50% EtOAc:PE) to afford Intermediate 13 (6.2 g, 56% yield). MS (ESI) 439.4 [M+H] ⁺ . Intermediate 14 2-(chloromethyl)-5-(((8-((4-methoxybenzyl)oxy)quinolin-6-yl) thio)methyl)-4-methylthiazole [0122] To a stirred 14.1 mmol) in DCM (50 mL) was added SOCl2 (2.0 mL, 28.2 mmol) dropwise at 0 °C. The mixture was stirred at rt for 2 h. Progress of the reaction was monitored by TLC. After completion, the reaction was quenched with sat. aq. sodium bicarbonate solution (50 mL) and then extracted with EtOAc (2 x 50 mL). The combined organic layers were washed with brine, dried (Na ₂ SO ₄ ), filtered and evaporated to afford Intermediate 14 (7.0 g, crude) as a light-yellow oil. The obtained crude was used for next step without further purification. MS (ESI) 457.2 [M+H] ⁺ . Intermediate 15 S-((5-(((8-((4-methoxybenzyl)oxy)quinolin-6-yl)thio)methyl)- 4-methylthiazol-2-yl)methyl) ethanethioate [0123] To a stirred so .7 mmol) in ACN (40 mL) were added potassium ethanethioate (1.9 g, 17.5 mmol) and KI (1.4 mg, 8.7 mmol) at 0 °C. The mixture was stirred at rt for 2 h. Progress of the reaction was monitored by TLC and LCMS. After completion, the reaction was quenched with water (50 mL) and extracted with EtOAc (2 x 30 mL). The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated. The crude material was purified by flash chromatography (SiO ₂ , 0-50% EtOAc:PE) to afford Intermediate 15 (3.0 g, 59%). MS (ESI) 497.3 [M+H] ⁺ . Intermediate 16 Methyl 6-chloro-7-(1-ethyl-5-((((5-(((8-((4-methoxybenzyl)oxy)quino lin-6-yl)thio)methyl)-4- methylthiazol-2-yl)methyl)thio)methyl)-3-methyl-1H-pyrazol-4 -yl)-3-(3-hydroxypropyl)-1- methyl-1H-indole-2-carboxylate [0124] To a st 75 mmol) in MeOH (20 mL) and THF (15 mL) was added K ₂ CO ₃ (3.6 g, 26.2 mmol), and the mixture was degassed with argon for 10 min. In a separate flask Intermediate 9 (4.1 g, 8.31 mmol) in THF (20 mL) was degassed with argon for 10 min. and this solution was added to the previous mixture dropwise. The mixture was stirred at rt for 16 h. Progress of the reaction was monitored by TLC and LCMS. After completion, the mixture was diluted with water (50 mL) and extracted with DCM (3 x 30 mL). The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated. The crude material was purified by flash chromatography (SiO ₂ , 0-70% EtOAc:PE) to afford Intermediate 16 (4.5 g, 60%). MS (ESI) 856.4 [M+H] ⁺ . Intermediate 17 Methyl 6-chloro-7-(1-ethyl-5-((((5-(((8-hydroxyquinolin-6-yl)thio)m ethyl)-4-methylthiazol-2- yl)methyl)thio)methyl)-3-methyl-1H-pyrazol-4-yl)-3-(3-hydrox ypropyl)-1-methyl-1H-indole-2- carboxylate [0125] To a stirred solution of Intermediate 16 (4.5 g, 5.2 mmol) in DCM (40 mL) was added TFA (4 mL, 52.6 mmol) dropwise at 0 °C. The mixture was stirred at rt for 3 h. Progress of the reaction was monitored by TLC and LCMS. After completion, the mixture was concentrated under reduced pressure. The reaction was quenched with sat. sodium bicarbonate solution (50 mL) and then extracted with DCM (2 x 30 mL). The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated. The crude material was purified by flash chromatography (SiO ₂ , 0-90% EtOAc:PE) to afford Intermediate 17 (3.5 g, 92%). MS (ESI) 736.2 [M+H] ⁺ . Intermediate 18 Methyl 1 ⁶ -chloro-2 ¹ -ethyl-1 ¹ ,2 ³ ,6 ⁴ -trimethyl-1 ¹ H,2 ¹ H-10-oxa-4,8-dithia-6(2,5)-thiazola-9(6,8)- quinolina-1(7,3)-indola-2(4,5)-pyrazolacyclotridecaphane-1 ² -carboxylate [0126] A solution o mol) in toluene (15 mL) and THF (5.0 mL) was degassed with argon for 10 min. and was then further stirred at 90 °C for 10 min. To this solution was added di-tert-butyl (E)-diazene-1,2-dicarboxylate (813 mg, 3.53 mmol) and TPP (712 mg, 3.53 mmol) at 90 °C. The mixture was stirred at 90 °C for 2 h. Progress of the reaction was monitored by TLC and LCMS. After completion, the reaction was quenched with water (40 mL) and then extracted it with EtOAc (2 x 30 mL). The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated. The crude material was purified by flash chromatography (SiO ₂ , 0-70% EtOAc:PE) to afford Intermediate 18 (1.0 g, 26%). MS (ESI) 718.2 [M+H] ⁺ . Intermediate 19A Methyl 1 ⁶ -chloro-2 ¹ -ethyl-1 ¹ ,2 ³ ,6 ⁴ -trimethyl-9 ¹ ,9 ² ,9 ³ ,9 ⁴ -tetrahydro-1 ¹ H,2 ¹ H-10-oxa-4,8-dithia- 6(2,5)-thiazola-9(6,8)-quinolina-1(7,3)-indola-2(4,5)-pyrazo lacyclotridecaphane-1 ² -carboxylate Intermediate 19B Methyl 1 ⁶ -chloro-2 ¹ -ethyl-1 ¹ ,2 ³ ,6 ⁴ -trimethyl-9 ¹ ,9 ² ,9 ³ ,9 ⁴ -tetrahydro-1 ¹ H,2 ¹ H-10-oxa-4,8-dithia- 6(2,5)-thiazola-9(6,8)-quinolina-1(7,3)-indola-2(4,5)-pyrazo lacyclotridecaphane-1 ² -carboxylate [0127] To a stirred 50 mg, 0.62 mmol) in MeOH and AcOH (1:1, 6 mL) was added NaCNBH ₃ (395 mg, 6.27 mmol) at rt. The mixture was stirred at rt for 3 h. Progress of the reaction was monitored by TLC and LCMS. After completion, the mixture was concentrated under reduced pressure. The reaction was quenched with sat. sodium bicarbonate solution (20 mL) and then extracted with EtOAc (2 x 20 mL). The combined organic layers were separated, dried (Na ₂ SO ₄ ), filtered and evaporated. The crude material was purified by flash chromatography (SiO2, 0-40% EtOAc:PE) to afford racemic methyl 1 ⁶ -chloro-2 ¹ -ethyl- 1 ¹ ,2 ³ ,6 ⁴ -trimethyl-9 ¹ ,9 ² ,9 ³ ,9 ⁴ -tetrahydro-1 ¹ H,2 ¹ H-10-oxa-4,8-dithia-6(2,5)-thiazola-9(6,8)- quinolina-1(7,3)-indola-2(4,5)-pyrazolacyclotridecaphane-1 ² -carboxylate (295 mg, 66%). MS (ESI) 722.5 [M+H] ⁺ . [0128] The atropisomers were separated by chiral SFC chromatography (Chiralcel- OX-H (30 x 250 mm), 40% CH ₃ CN:MeOH; 4:1) to give peak 1 (Intermediate 19A, 150 mg) and peak 2 (Intermediate 19B, 150 mg). Intermediate 19A: 99.8% chiral purity; MS (ESI) 722.5 [M+H] ⁺ . Intermediate 19B: 99.6% chiral purity; MS (ESI) 722.5 [M+H] ⁺ . The absolute stereochemistry of Intermediate 19A and Intermediate 19B was arbitrarily assigned (Intermediates 19A and 19B may be the atropisomers of the compounds depicted). Example 1A 1 ⁶ -Chloro-2 ¹ -ethyl-1 ¹ ,2 ³ ,6 ⁴ -trimethyl-9 ¹ ,9 ² ,9 ³ ,9 ⁴ -tetrahydro-1 ¹ H,2 ¹ H-10-oxa-4,8-dithia-6(2,5)- thiazola-9(6,8)-quinolina-1(7,3)-indola-2(4,5)-pyrazolacyclo tridecaphane-1 ² -carboxylic acid [0129] To a stirre 19A (130 mg, 0.18 mmol) in MeOH:THF:H2O (1:1:1, 6 mL) was added LiOH•H2O (113 mg, 2.70 mmol) at rt, and the mixture was stirred at 70 °C for 2 h. Progress of the reaction was monitored by TLC and LCMS. After completion, the mixture was evaporated under reduced pressure to obtain the crude product. The crude material obtained was acidified to pH 2 using 2.0 N aqueous HCl. An off-white precipitate was formed and filtered. The product washed with ice cold water, dried in vacuum to afford Example 1A (75 mg, 56%). MS (ESI) 708.6 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 13.36 (bs, 1H), 7.80 (d, J = 8.8 Hz, 1H), 7.11 (d, J = 8.4 Hz H), 6.63 (s, 1H), 6.33 (s, 1H), 4.16-4.06 (m, 4H), 3.77-3.57 (m, 5H), 3.31-3.20 (m, 7H), 3.16-3.08 (m, 1H), 2.66-2.64 (m, 2H), 2.17 (bs, 1H), 2.07-1.97 (m, 4H), 1.88 (s, 3H), 1.85 (bs, 2H), 1.36 (t, J = 7.2 Hz, 3H).

Example 1B 1 ⁶ -Chloro-2 ¹ -ethyl-1 ¹ ,2 ³ ,6 ⁴ -trimethyl-9 ¹ ,9 ² ,9 ³ ,9 ⁴ -tetrahydro-1 ¹ H,2 ¹ H-10-oxa-4,8-dithia-6(2,5)- thiazola-9(6,8)-quinolina-1(7,3)-indola-2(4,5)-pyrazolacyclo tridecaphane-1 ² -carboxylic acid [0130] To a stirre 19B (120 mg, 0.16 mmol) in MeOH:THF:H ₂ O (1:1:1, 6 mL) was added LiOH•H ₂ O (105 mg, 2.49 mmol) at rt, and the mixture was stirred at 70 °C for 2 h. Progress of the reaction was monitored by TLC and LCMS. After completion, the mixture was evaporated under reduced pressure to obtain the crude product. The crude material obtained was acidified to pH 2 using 2.0 N aqueous HCl, and an off-white precipitate was formed. The product was filtered, washed with ice cold water and dried in vacuum to afford Example 1B (42 mg, 34%). MS (ESI) 708.6 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d6) δ 13.25 (bs,1H), 7.75 (d, J = 8.8 Hz, 1H), 7.09 (d, J = 8.4 Hz, 1H), 6.68 (s, 1H), 6.14 (s, 1H), 5.33 (bs, 1H), 4.13-3.91 (m, 4H), 3.64-3.52 (m, 5H), 3.48 (s, 3H), 3.28-3.11 (m, 5H), 2.67-2.62 (m, 2H), 2.14 (bs, 1H), 1.90 (bs, 1H),1.90 - 1.89 (m, 6H), 1.78 (bs, 2H), 1.36 (t, J = 7.2 Hz, 3H). [0131] As provided herein, both atropisomers, Example 1A and Example 1B, were obtained. The absolute stereochemistry of Example 1A and Example 1B was arbitrarily assigned. Intermediate 20 Methyl 3-(3-acetoxypropyl)-6-chloro-7-(1-(4-methoxybenzyl)-5-(((4- methoxybenzyl)oxy)methyl)-3-methyl-1H-pyrazol-4-yl)-1-methyl -1H-indole-2-carboxylate [0132] To a degassed solution of 1-(4-methoxybenzyl)-3-(((4- methoxybenzyl)oxy)methyl)-5-methyl-4-(4,4,5,5-tetramethyl-1, 3,2-dioxaborolan-2-yl)-1H- pyrazole (WO 2020/185606 A1) (34 g, 71.12 mmol) in 1,4-dioxane:water (300 mL: 40 mL) were added methyl 3-(3-acetoxypropyl)-7-bromo-6-chloro-1-methyl-1H-indole-2-ca rboxylate (WO 2020/185606 A1) (14.26 g, 35.56 mmol) and Cs2CO3 (34.67 g, 106.68 mmol). The solution was degassed with argon for 20 mins. Dichloro[1 1'-bis(di-tert-butylphosphino)ferrocene] palladium(II) (4.107 g, 0.556 mmol) was added, and the mixture was degassed again for 10 min. The mixture was heated at 100 °C for 2 h. The progress of reaction was monitored by TLC and LCMS. After completion, the mixture was cooled to rt and then filtered through a pad of Celite. The obtained filtrate was diluted with water (200 mL) and extracted with EtOAc (2 x 300 mL). The combined organic layers were washed with brine, dried (Na ₂ SO ₄ ), filtered and evaporated. The crude material was purified by flash chromatography (SiO2, 0-30% EtOAc:PE) to afford Intermediate 20 (8.8 g, 37%) as a brown viscous liquid. MS (ESI) 674.69 [M+H] ⁺ . Intermediate 21 Methyl 3-(3-acetoxypropyl)-6-chloro-7-(5-(hydroxymethyl)-1-(4-metho xybenzyl)-3-methyl-1H- pyrazol-4-yl)-1-methyl-1H-indole-2-carboxylate [0133] To a stirred solutio g, 12.89 mmol) in DCM (130 mL) was added TFA (7 mL, 90.28 mmol) dropwise at 0 °C. The mixture was stirred at rt for 2 h. Progress of the reaction was monitored by TLC and LCMS. After completion, the mixture was diluted with DCM (200 mL) and then washed with sat. aq. NaHCO3 solution (2 x 100 mL) and brine (2 x 100 mL). The organic layer was separated, dried over anhydrous Na ₂ SO ₄ , filtered and evaporated to get a semi pure compound (8.4 g). The obtained compound (8.4 g) was dissolved in MeOH (78 mL). K2CO3 (3.39 g, 24.566 mmol) was added at rt, and the mixture was stirred for 2 h. The progress of the reaction was monitored by TLC. The mixture was filtered and evaporated. The crude material obtained was diluted with CH ₂ Cl ₂ (200 mL), washed with water (2 x 100 mL), dried (Na ₂ SO ₄ ), filtered and evaporated. The crude material was purified by flash chromatography (SiO2, 0-30% EtOAc:PE) to afford Intermediate 21 (4.9 g, 68%). MS (ESI) 554.1 [M+H] ⁺ . Intermediate 22 Methyl 3-(3-acetoxypropyl)-6-chloro-7-(5-(chloromethyl)-1-(4-methox ybenzyl)-3-methyl-1H- pyrazol-4-yl)-1-methyl-1H-indole-2-carboxylate [0134] To a stirred solutio 42 mmol) in DCM (40 mL) under argon was added SOCl2 (0.645 mL, 8.90 mmol) dropwise at 0 °C. The mixture was stirred at rt for 30 min. Progress of the reaction was monitored by TLC. The mixture was diluted with DCM (100 mL) and washed with sat. NaHCO3 solution (2 x 50 mL). The organic layer was separated, dried over anhydrous Na2SO4, filtered and evaporated to afford semi pure Intermediate 22 (4.2 g mmol, 99%) as a light-yellow liquid. The compound was used in next step without further purification. MS (ESI) 572.54 [M+H] ⁺ . Intermediate 23 Methyl 3-(3-acetoxypropyl)-6-chloro-7-(5-(iodomethyl)-1-(4-methoxyb enzyl)-3-methyl-1H- pyrazol-4-yl)-1-methyl-1H-indole-2-carboxylate [0135] To a stirred solut ermediate 22 (4.1 g, 7.36 mmol) in dry MeCN (90 mL) was added NaI (1.985 g, 13.24 mmol) at rt, and the mixture was stirred to 80 ^o C for 2.5 h. Progress of the reaction was monitored by TLC. After completion, the solvent was evaporated. The mixture was diluted with water (200 mL) and extracted with EtOAc (2 x 200 mL). The combined organic layers were separated, dried (Na ₂ SO ₄ ), filtered and evaporated to afford semi-pure Intermediate 23 (4.3 g, 90%) as a light-yellow liquid. This material was used in next step without further purification. MS (ESI) 664.53 [M+H] ⁺ . Intermediate 24 Ethyl 5-(((7-fluoro-4-hydroxynaphthalen-2-yl)thio)methyl)-1-methyl -1H-pyrazole-3-carboxylate [0136] To a degas ylsilyl)oxy)-7-fluoronaphthalen- 2-yl trifluoromethanesulfonate (44 g, 0.103 mol) in 1,4-dioxane (880 mL):water (44 mL) were added ethyl 5-((acetylthio)methyl)-1-methyl-1H-pyrazole-3-carboxylate (WO 2018/178226 A1) (22.6 g, 0.093 mol), K ₂ CO ₃ (15 g, 0.108 mol), XPhos (4.93 g, 0.01 mol) and Pd ₂ (dba) ₃ (4.75 g, 0.005 mol). The solution was degassed with argon for another 15 min. The mixture was heated at 100 °C for 3 h. The mixture was cooled to rt, diluted with EtOAc (250 mL) and passed through a Celite pad. The Celite pad with EtOAc (200 mL). The organic layer was washed with brine, dried (Na ₂ SO ₄ ), filtered and evaporated. The crude material was purified by flash chromatography (SiO2, 0-30% EtOAc:PE) to afford Intermediate 24 (25 g, 67 %). MS (ESI) 361.31 [M+H] ⁺ . Intermediate 25 6-Fluoro-3-(((3-(hydroxymethyl)-1-methyl-1H-pyrazol-5-yl)met hyl)thio)naphthalen-1-ol [0137] To a stirred 0 g, 0.083 mol) in THF (300 mL) was added LiAlH ₄ (2.4 M in THF, 52 mL, 0.124 mol) dropwise for about 15 min at 0 °C. The mixture brought to rt and stirred for 1 h. After completion of the reaction by TLC, the mixture was cooled to 0 °C. The reaction was quenched with sat. Na ₂ SO ₄ solution (25 mL). The precipitated product were removed by filtration. The filtrate was dried over Na ₂ SO ₄ , filtered and evaporated to get a crude compound. The crude material was purified by flash chromatography (SiO ₂ , 0-30% EtOAc:PE) to afford Intermediate 25 (17 g, 64%). MS (ESI) 319.25 [M+H] ⁺ . Intermediate 26 3-(((3-(Chloromethyl)-1-methyl-1H-pyrazol-5-yl)methyl)thio)- 6-fluoronaphthalen-1-ol [0138] To a stirred g, 25.15 mmol) in DMF (80 mL) under argon was added LiCl (2.7 g, 125.78 mmol), 2,6-lutidine (12 mL, 100.56 mmol) and MeSO ₂ Cl (4.2 mL, 50.28 mmol) at 0 °C. The mixture brought to rt and stirred for 2 h. After completion of the reaction by TLC, the reaction was quenched with ice cold water (300 mL). The mixture was extracted with EtOAc (2 x 200 mL). The organic layer was washed with brine (50 mL), dried over Na2SO4, filtered, and evaporated to afford Intermediate 26 (8.5 g, crude) as brown liquid. The material was used for the next step without further purification. MS (ESI) 337.26 [M+H] ⁺ . Intermediate 27 3-(((3-(Chloromethyl)-1-methyl-1H-pyrazol-5-yl)methyl)thio)- 6-fluoronaphthalen-1-yl acetate [0139] To a stirred g, 25.29 mmol) in acetonitrile (85 mL) was added DMAP (0.308 g, 2.53 mmol) and Ac2O (3.35 g, 32.88 mmol) at 0 °C. The mixture was stirred at rt for 2 h. After completion of the reaction by TLC, the reaction was quenched with water (100 mL) and extracted with EtOAc (2 x 100 mL). The combined organic layers were washed with brine, dried (Na ₂ SO ₄ ), filtered and evaporated to afford Intermediate 27 (10 g, crude) as a brown liquid. The material was used for the next step without further purification. MS (ESI) 379.21 [M+H] ⁺ . Intermediate 28 3-(((3-((Acetylthio)methyl)-1-methyl-1H-pyrazol-5-yl)methyl) thio)-6-fluoronaphthalen-1-yl acetate [0140] To a degas (10 g, 26.45 mmol) in ACN (100 mL) was added KSAc (4.4 g, 26.45 mmol) and KI (6 g, 52.91 mmol) at 0 °C. The mixture was allowed to stir at rt for 16 h. After completion of the reaction by TLC, the reaction was quenched with water (100 mL) and extracted with EtOAc (2 x 100 mL). The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated. The crude material was purified by flash chromatography (SiO ₂ , 0-20% EtOAc:PE) to afford Intermediate 28 (4.7 g, 45% over 3 steps). MS (ESI) 419.34 [M+H] ⁺ . Intermediate 29 Methyl 6-chloro-7-(5-((((5-(((7-fluoro-4-hydroxynaphthalen-2-yl)thi o)methyl)-1-methyl-1H- pyrazol-3-yl)methyl)thio)methyl)-1-(4-methoxybenzyl)-3-methy l-1H-pyrazol-4-yl)-3-(3- hydroxypropyl)-1-methyl-1H-indole-2-carboxylate [0141] To a st (4 g, 6.16 mmol) in degassed MeOH (20 mL) and THF (5 mL) was added K2CO3 (2.03 g, 14.718 mmol). The mixture was degassed with argon for 10 min. In a separate flask, Intermediate 28 (2.465 g, 6.16 mmol) in methanol (20 mL) THF (5 mL) was degassed with argon for 10 min. The Intermediate 28 solution was added to Intermediate 23 dropwise. The mixture was stirred at rt for 16 h. Progress of the reaction was monitored by TLC and LCMS. After completion, the mixture was diluted with CH ₂ Cl ₂ (300 mL) and then washed with water (100 mL) and brine (100 mL). The combined organic layer was washed with brine, dried (Na ₂ SO ₄ ), filtered and evaporated. The crude material was purified by flash chromatography (SiO2, 0-50% EtOAc:PE) to afford Intermediate 29 (3.7 g , 74%). MS (ESI) 828.79 [M+H] ⁺ . Intermediate 30 Methyl (Z)-1 ⁶ -chloro-9 ⁶ -fluoro-2 ¹ -(4-methoxybenzyl)-1 ¹ ,2 ³ ,6 ¹ -trimethyl-1 ¹ H,2 ¹ H,6 ¹ H-10-oxa- 4,8-dithia-1(7,3)-indola-2(4,5),6(3,5)-dipyrazola-9(3,1)-nap hthalenacyclotridecaphane-1 ² - carboxylate [0142] To a stirre g, 4.47 mmol) in DCM (37 mL) were added TPP (2.93 g, 11.18 mmol) and di-tert-butyl diazene-1,2-dicarboxylate (2.57 g, 11.18 mmol) at rt. The mixture was stirred at rt for 2 h. Progress of the reaction was monitored by TLC and LCMS. After completion, the reaction was quenched with water (50 mL) and extracted with DCM (2 x 150 mL). The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated to give semi-pure compound. This compound was triturated with MeOH (10 mL) to afford Intermediate 30 (1.1 g, 30.55%). MS (ESI) 810.54 [M+H] ⁺ . Intermediate 31 Methyl (Z)-1 ⁶ -chloro-9 ⁶ -fluoro-1 ¹ ,2 ³ ,6 ¹ -trimethyl-1 ¹ H,2 ¹ H,6 ¹ H-10-oxa-4,8-dithia-1(7,3)-indola- 2(4,5),6(3,5)-dipyrazola-9(3,1)-naphthalenacyclotridecaphane -1 ² -carboxylate [0143] To a stirred solution of Intermediate 30 (1.1 g, 1.36 mmol) in TFA (10 mL) in a pressure vessel was added anisole (10 mL) at rt. The mixture was stirred at 100 ^o C for 16 h. Progress of the reaction was monitored by TLC and LCMS. After completion, the mixture was concentrated under reduced pressure to afford Intermediate 31 (600 mg 65%). MS (ESI) 690.46 [M+H] ⁺ . Intermediate 32A Methyl (Z)-21-(2-((tert-butyldimethylsilyl)oxy)ethyl)-16-chloro-96- fluoro-1 ¹ ,2 ³ ,6 ¹ -trimethyl- 1 ¹ H,2 ¹ H,6 ¹ H-10-oxa-4,8-dithia-1(7,3)-indola-2(4,5),6(3,5)-dipyra zola-9(3,1)- naphthalenacyclotridecaphane-1 ² -carboxylate Intermediate 32B Methyl (Z)-2 ¹ -(2-((tert-butyldimethylsilyl)oxy)ethyl)-1 ⁶ -chloro-9 ⁶ -fluoro-1 ¹ ,2 ⁵ ,6 ¹ -trimethyl- 1 ¹ H,2 ¹ H,6 ¹ H-10-oxa-4,8-dithia-1(7,3)-indola-2(4,3),6(3,5)-dipyra zola-9(3,1)- naphthalenacyclotridecaphane-12-carboxylate [0144] To a .87 mmol) in ACN (10 mL) were added Cs2CO3 (452 mg, 1.392 mmol) and (2-bromoethoxy)(tert-butyl)dimethylsilane (517 mg, 2.175 mmol). The mixture was stirred at 100 °C for 16 h. Progress of reaction was monitored by TLC and LCMS. After completion, the reaction was quenched with water (50 mL) and extracted with EtOAc (2 x 150 mL). The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated. The crude material was purified by flash chromatography (SiO2, 0-30% EtOAc:PE) to afford Intermediate 32A (300 mg, 40%). MS (ESI) 848.44 [M+H] ⁺ and Intermediate 32B (350 mg, 47%). MS (ESI) 848.44 [M+H] ⁺ . Intermediate 33A Methyl (Z)-1 ⁶ -chloro-9 ⁶ -fluoro-2 ¹ -(2-hydroxyethyl)-1 ¹ ,2 ³ ,6 ¹ -trimethyl-1 ¹ H,2 ¹ H,6 ¹ H-10-oxa-4,8- dithia-1(7,3)-indola-2(4,5),6(3,5)-dipyrazola-9(3,1)-naphtha lenacyclotridecaphane-1 ² - carboxylate Intermediate 33B Methyl (Z)-1 ⁶ -chloro-9 ⁶ -fluoro-2 ¹ -(2-hydroxyethyl)-1 ¹ ,2 ³ ,6 ¹ -trimethyl-1 ¹ H,2 ¹ H,6 ¹ H-10-oxa-4,8- dithia-1(7,3)-indola-2(4,5),6(3,5)-dipyrazola-9(3,1)-naphtha lenacyclotridecaphane-1 ² - carboxylate [0145] To a stirre mmol) in THF (3 mL) was added 1M TBAF in THF (0.71 mL, 0.708 mmol) dropwise at 0 °C. The mixture was stirred at rt for 1 h. Progress of the reaction was monitored by TLC and LCMS. After completion, the reaction was quenched with water (50 mL) and extracted with EtOAc (2 x 150 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The obtained crude was purified by titration with n-pentane (20 mL) to afford racemic methyl (Z)-1 ⁶ - chloro-9 ⁶ -fluoro-2 ¹ -(2-hydroxyethyl)-1 ¹ ,2 ³ ,6 ¹ -trimethyl-1 ¹ H,2 ¹ H,6 ¹ H-10-oxa-4,8-dithia-1(7,3)- indola-2(4,5),6(3,5)-dipyrazola-9(3,1)-naphthalenacyclotride caphane-1 ² -carboxylate (200 mg, 80%). MS (ESI) 734.4 [M+H] ⁺ . [0146] The atropisomers were separated by chiral SFC chromatography (Chiralpak IG- 3(4.6 x 150 mm), 3µ, 30%, 0.2% 7 N methanolic ammonia in Acetonitrile:MeOH; 1:1)) to give peak 1 (Intermediate 33A, 80 mg) and peak 2 (Intermediate 33B, 80 mg). Intermediate 33A: 99.78% chiral purity; MS (ESI) 734.4 [M+H] ⁺ . Intermediate 33B: 99.65% chiral purity; MS (ESI) 734.4 [M+H] ⁺ . The absolute stereochemistry of Intermediate 33A and Intermediate 33B was arbitrarily assigned (Intermediate 33B may be the atropisomer of the compound depicted). Example 2A (Z)-1 ⁶ -chloro-9 ⁶ -fluoro-2 ¹ -(2-hydroxyethyl)-1 ¹ ,2 ³ ,6 ¹ -trimethyl-1 ¹ H,2 ¹ H,6 ¹ H-10-oxa-4,8-dithia- 1(7,3)-indola-2(4,5),6(3,5)-dipyrazola-9(3,1)-naphthalenacyc lotridecaphane-1 ² -carboxylic acid [0147] To a stir 3A (80 mg, 0.113 mmol) in MeOH:THF:H ₂ O (1:1:1, 6 mL) was added LiOH•H ₂ O (71 mg, 1.70 mmol) at 0 °C. The mixture was stirred at rt for 3 h. Progress of the reaction was monitored by TLC and LCMS. After completion, the mixture was evaporated, and the crude was acidified to pH ~6 using 2N aqueous HCl (~3 mL). The resulting precipitate was collected by filtration, washed with water (5 mL) and dried under vacuum to afford Example 2A (42 mg, 52%) (99.55% chiral purity). ¹ H NMR (400 MHz, DMSO-d6) δ 13.5 (bs, 1H), 8.19-8.16 (m, 1H), 7.76 (d, J = 8.8 Hz, 1H), 7.52-7.48 (dd, J = 2.4, 8.8 Hz, 1H), 7.38-7.30 (m, 2H), 7.04 (d, J = 8.8 Hz, 1H), 6.63 (s, 1H), 4.87-4.84 (m, 1H), 4.73 (s, 1H), 4.30-4.00 (m, 5H), 3.98-3.88 (m, 1H), 3.68 (m, 5H), 3.44 (s, 5H), 3.28 (s, 1H), 3.13-3.09 (d, J = 15.6 Hz, 2H), 2.99-2.96 (d, J = 14 Hz, 1H), 2.35-2.32 (m, 1H), 2.21 (bs, 1H), 1.89 (s, 3H). MS (ESI) 720.35 [M+H] ⁺ . Example 2B (Z)-1 ⁶ -chloro-9 ⁶ -fluoro-2 ¹ -(2-hydroxyethyl)-1 ¹ ,2 ³ ,6 ¹ -trimethyl-1 ¹ H,2 ¹ H,6 ¹ H-10-oxa-4,8-dithia- 1(7,3)-indola-2(4,5),6(3,5)-dipyrazola-9(3,1)-naphthalenacyc lotridecaphane-1 ² -carboxylic acid [0148] To a stir 3B (80 mg, 0.113 mmol) in MeOH:THF:H ₂ O (1:1:1, 6 mL) was added LiOH•H ₂ O (71 mg, 1.70 mmol) at 0 °C. The mixture was stirred at rt for 20 h. Progress of reaction was monitored by TLC and LCMS. After completion, the mixture was evaporated, and the crude was acidified to pH ~6 using 2N aqueous HCl (~3 mL). The resulting precipitate was collected by filtration, washed with water (5 mL) and dried under vacuum to afford Example 2B (44 mg, 54%, 98.49% chiral purity). ¹ H NMR (400 MHz, DMSO-d6) δ 13.5 (bs, 1H), 8.19 - 8.16 (m, 1H), 7.76 (d, J = 8.4 Hz, 1H), 7.52-7.48 (m, 1H), 7.38-7.30 (m, 2H), 7.04 (d, J = 8.8 Hz, 1H), 6.63 (s, 1H), 4.87-4.84 (m, 1H), 4.73 (s, 1H), 4.30- 4.00 (m, 5H), 3.89-3.88 (m, 1H), 3.73-3.71 (m, 5H), 3.49-3.45 (m, 5H), 3.36-3.28 (m, 1H), 3.16- 3.09 (m, 2H), 2.99-2.96 (d, J = 14 Hz, 1H), 2.36-2.32 (m, 1H), 2.21-2.19 (bs, 1H), 1.89 (s, 3H). MS (ESI) 720.35 [M+H] ⁺ . [0149] As provided herein, both atropisomers, Example 2A and Example 2B, were obtained. The absolute stereochemistry of Example 2A and Example 2B was arbitrarily assigned. Intermediate 34A Methyl (Z)-16-chloro-9 ⁶ -fluoro-2 ¹ -(2-hydroxyethyl)-1 ¹ ,2 ⁵ ,6 ¹ -trimethyl-1 ¹ H,2 ¹ H,6 ¹ H-10-oxa-4,8- dithia-1(7,3)-indola-2(4,3),6(3,5)-dipyrazola-9(3,1)-naphtha lenacyclotridecaphane-1 ² - carboxylate Methyl (Z)-16-chloro-9 ⁶ -f hyl-1 ¹ H,2 ¹ H,6 ¹ H-10-oxa-4,8- dithia-1(7,3)-indola- , , , - pyrazo a- , -nap a enacyclotridecaphane-1 ² - carboxylate [0150] To a sti g, 0.35 mmol) in THF (3 mL) was added 1M TBAF in THF(0.7 mL, 0.708 mmol ) dropwise at 0 °C. The mixture was stirred at rt for 1 h. Progress of the reaction was monitored by TLC and LCMS. After completion, the reaction was quenched with water (50 mL) and extracted with EtOAc (2 x 20 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The obtained crude was triturated with n- pentane (10 mL) to afford racemic methyl (Z)- 16-chloro-9 ⁶ -fluoro-2 ¹ -(2-hydroxyethyl)-1 ¹ ,2 ⁵ ,6 ¹ -trimethyl-1 ¹ H,2 ¹ H,6 ¹ H-10-oxa-4,8-dithia- 1(7,3)-indola-2(4,3),6(3,5)-dipyrazola-9(3,1)-naphthalenacyc lotridecaphane-1 ² -carboxylate (120 mg, 60%). MS (ESI) 734.5 [M+H] ⁺ . [0151] The atropisomers were separated by chiral SFC chromatography (Chiralpak IG-3(4.6 x 150 mm), 3µ, 40% (0.2% 7 N methanolic ammonia in Acetonitrile:MeOH; 1:1) to give peak 1 (Intermediate 34A, 40 mg) and peak 2 (Intermediate 34B, 40 mg). Intermediate 34A: 99.66% chiral purity; MS (ESI) 734.5 [M+H] ⁺ . Intermediate 34B: 98.09% chiral purity; MS (ESI) 734.5 [M+H] ⁺ . The absolute stereochemistry of Intermediate 34A and Intermediate 34B was arbitrarily assigned. Example 3A (Z)-1 ⁶ -chloro-9 ⁶ -fluoro-2 ¹ -(2-hydroxyethyl)-1 ¹ ,2 ⁵ ,6 ¹ -trimethyl-1 ¹ H,2 ¹ H,6 ¹ H-10-oxa-4,8-dithia- 1(7,3)-indola-2(4,3),6(3,5)-dipyrazola-9(3,1)-naphthalenacyc lotridecaphane-1 ² -carboxylic acid [0152] To a (40 mg, 0.0567 mmol) in MeOH:THF:H2O (1:1:1, 6 mL) was added LiOH•H2O (35 mg, 0.851 mmol) at 0 °C. The mixture was stirred at 70 °C for 2 h. After completion, the solvent was evaporated. The aqueous layer was acidified to pH ~6 using 2N aqueous HCl (~3 mL). The resulting precipitate was collected by filtration, washed with water (5 mL) and dried under vacuum to afford Example 3A (17.6 mg, 46%, 98.2% chiral purity). ¹ H NMR (400 MHz, DMSO-d6) δ 13.5 (bs, 1H), 8.15-8.11 (m, 1H), 7.88 (d, J = 8.4 Hz, 1H ), 7 1 (dd, J = 2.4, 8.0 Hz, 1H ), 7.35-7.31 (m, 2H), 7.16 (d, J = 8.4 Hz, 1H), 6.68 (s, 1H), 4.75 (bs, 2H), 4.30 (bs, 2H), 4.16-4.08 (m, 3H), 3.85 (bs, 1H), 3.73-3.70 (m, 5H), 3.46-3.37 (m, 5H), 3.26-3.07 (m, 3H), 2.94-2.91 (m, 1H), 2.37 (bs, 1H), 2.23 (bs, 1H), 1.97 (s, 3H). MS (ESI) 720.3 [M+H] ⁺ .

Example 3B (Z)-1 ⁶ -chloro-9 ⁶ -fluoro-2 ¹ -(2-hydroxyethyl)-1 ¹ ,2 ⁵ ,6 ¹ -trimethyl-1 ¹ H,2 ¹ H,6 ¹ H-10-oxa-4,8-dithia- 1(7,3)-indola-2(4,3),6(3,5)-dipyrazola-9(3,1)-naphthalenacyc lotridecaphane-1 ² -carboxylic acid [0153] To a (40 mg, 0.0567 mmol) in MeOH:THF:H ₂ O (1:1:1, 6 mL) was added LiOH•H ₂ O (35 mg, 0.851 mmol) at 0 °C. The mixture was stirred at 70 °C for 3 h. After completion, the solvent was evaporated. The aqueous layer was acidified to pH ~6 using 2N aqueous HCl (~3 mL). The resulting precipitate was collected by filtration, washed with water (5 mL) and dried under vacuum to afford Example 3B (19.1 mg, 48%, 98.2% chiral purity). ¹ H NMR (400 MHz, DMSO-d6) δ 13.33 (bs, 1H), 8.15-8.11 (m, 1H), 7.88 (d, J = 8.4 Hz, 1H ), 1 (dd, J = 2.4, 8.0 Hz, 1H ), 7.35-7.31 (m, 2H), 7.16 (d, J = 8.8 Hz, 1H), 6.68 (s, 1H), 4.75 (s, 2H), 4.30 (s, 2H), 4.16-4.08 (m, 3H), 3.85 (bs, 1H), 3.73-3.70 (m, 5H), 3.46-3.37 (m, 5H), 3.26-3.07 (m, 3H), 2.94-2.91 (m, 1H), 2.37 (bs, 1H), 2.23 (bs, 1H), 1.97 (s, 3H). MS (ESI) 720.3 [M+H] ⁺ . [0154] As provided herein, both atropisomers, Example 3A and Example 3B, were obtained. The absolute stereochemistry of Example 3A and Example 3B was arbitrarily assigned. Intermediate 1-1 (R,E)-N-(3-bromo-2-methyl-6,7-dihydropyrazolo[1,5-a]pyridin- 4(5H)-ylidene)-2- methylpropane-2-sulfinamide [0155] To a stirred solu o-2-methyl-6,7-dihydro-5H-pyrazolo[1,5- a]pyridin-4-one (30 g, 131 mmol) and (R)-2-methylpropane-2-sulfinamide (31.7 g, 262 mmol) in THF (262 mL). at 0 ^o C was added titanium(IV) triethanolate propan-2-olate (95 g, 393 mmol). The mixture was heated at 65 ^o C for 15 h. The mixture was cooled to 0 ^o C and then brine (300 mL) was added followed by EtOAc (500 mL). Formation of some precipitate was observed, and the mixture was filtered through Celite. The filtrate was collected, washed the Celite with EtOAc (200 mL) and triturated the Celite with EtOAc (4 x 100 mL). The organic layer was dried (Na2SO4), filteredand concentrated. The crude material was purified by flash chromatography (SiO ₂ , 0-100% EtOAc:PE) to afford Intermediate 1-1 (22 g, 50.6%). MS (APCI) 332.0 [M+H] ⁺ . Intermediate 2A-1 (R)-N-((R)-3-bromo-2-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a ]pyridin-4-yl)-2-methylpropane- 2-sulfinamide Intermediate 2B-1 (R)-N-((S)-3-bromo-2-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a ]pyridin-4-yl)-2-methylpropane- 2-sulfinamide [0156] To a solution of Int 0.15 g, 30.5 mmol) in THF (61.1 mL) at - 78 °C, was added diisobutylaluminum hydride solution (89 mL, 89 mmol) (1 M in THF) using an addition funnel (85 mL/h, took ~1 h for addition). The reaction was stirred for 2 h at -78 °C. The mixture was warmed to 0 °C and then diethyl ether (250 mL) was added, followed by water (3.56 mL, very slowly, 15% NaOH (3.56 mL) and a second portion of water (8.9 mL, Fieser method of DIBAL-H work up). The mixture was stirred at room temperature (rt) for 30 min. MgSO ₄ (40 mg) was added, and the mixture was stirred for 20 min., followed by filtration. The product was washed with ether (100 mL) and then ethyl acetate (100 mL). The filtrate was collected, dried over Na ₂ SO ₄ , concentrated and purified by silica gel chromatography using 0-100% ethyl acetate in hexane to afford Intermediate 2A-1 (5.2 g, 50.9%) and Intermediate 2B-1 at a ratio 9:1. Intermediate 2A-1: MS (APCI) 219.2 [M+H] ⁺ . Intermediate 2B-1: LCMS. MS (APCI) 219.2 [M+H] ⁺ . The absolute stereochemistry of Intermediate 2A-1 and Intermediate 2B-1 was arbitrarily assigned. Intermediate 3 ^-1 Methyl 6-chloro-3-(3-methoxy-3-oxopropyl)-7-(4,4,5,5-tetramethyl-1, 3,2-dioxaborolan-2-yl)- 1H-indole-2-carboxylate [0157] To a stirred solu -6-chloro-3-(3-methoxy-3-oxopropyl)- 1H-indole-2-carboxylate (20.0 g, 53.7 mmol) and 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2- dioxaborolane) (27.2 g, 1.7 mmol) in 1,4 dioxane (200 mL) was purged with argon for 10 min was added PdCl ₂ (dppf)•DCM adduct (2.15 g, 2.18 mmol) and KOAc (10.5 g, 170 mmol) at rt. The mixture was stirred at 65 °C for 16 h. Progress of the reaction was monitored by TLC and LCMS. After completion, the mixture was cooled to rt and then diluted with ice cold water (300 mL). The mixture was extracted with EtOAc (2 x 300 mL). The combined organic layers were washed with brine, dried (Na ₂ SO ₄ ), filtered and evaporated. The crude material was purified by flash chromatography (SiO2, 0-5% EtOAc:PE) to afford Intermediate 3-1 (10.0 g, 44%). MS (ESI) 422.4 [M+H] ⁺ . Intermediate 4-1 Methyl 7-((R)-4-(((R)-tert-butylsulfinyl)amino)-2-methyl-4,5,6,7-te trahydropyrazolo[1,5- a]pyridin-3-yl)-6-chloro-3-(3-methoxy-3-oxopropyl)-1H-indole -2-carboxylate [0158] A solution of Intermediate 3-1 (32.0 g, 76.0 mmol) and Intermediate 2A-1 (30.0 g, 91.2 mmol) in 1,4 dioxane (250 mL) and water (50.0 mL) was purged with argon for 10 min. To this mixture was added SPhos-Pd-G3 (6.0 g,7.6 mmol), and K3PO4 (32.0 g, 152.0 mmol). The mixture was stirred at 60 °C for 6 h. Progress of the reaction was monitored by TLC and LCMS. After completion, the mixture was cooled to rt. The reaction was quenched with ice cold water (300 mL) and extracted with EtOAc (2 x 300 mL). The combined organic layers were washed with brine, dried (Na ₂ SO ₄ ), filtered and evaporated. The crude material was purified by flash chromatography (SiO2, 0-90% EtOAc:PE) to afford Intermediate 4-1 (32.0 g, 41%). MS (ESI) 549.4 [M+H] ⁺ . The absolute stereochemistry of Intermediate 4-1 was arbitrarily assigned. Intermediate 5-1 Methyl 7-((R)-4-(((R)-tert-butylsulfinyl)amino)-2-methyl-4,5,6,7-te trahydropyrazolo[1,5- a]pyridin-3-yl)-6-chloro-3-(3-methoxy-3-oxopropyl)-1-methyl- 1H-indole-2-carboxylate [0159] To a stirred (35.0 g, 63.9 mmol) in ACN (350 mL) was added Cs2CO3 (41.0 g, 127.9 mmol) at 0 °C. The mixture was stirred at 0 °C for 10 min. MeI (8.0 mL, 127.9 mmol) was added drop wise at 0 °C. The mixture was stirred at rt for 2.5 h. Progress of the reaction was monitored by TLC and LCMS. After completion, the reaction was quenched with water (200 mL) and extracted with EtOAc (2 x 200 mL). The combined organic layers were washed with brine, dried (Na ₂ SO ₄ ), filtered and evaporated. The crude material was purified by flash chromatography (SiO ₂ , 0-90% EtOAc:PE) to afford Intermediate 5-1 (28.0 g, 87%) as a light brown oil. MS (ESI) 564.4 [M+H] ⁺ . The absolute stereochemistry of Intermediate 5-1 was arbitrarily assigned. Intermediate 6-1 Methyl (R)-7-(4-amino-2-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyr idin-3-yl)-6-chloro-3-(3- methoxy-3-oxopropyl)-1-methyl-1H-indole-2-carboxylate [0160] To a stirred so (31.0 g, 55.1 mmol) in dioxane (150 mL) was added 4.0 M HCl in dioxane (300 mL) dropwise at 0 °C. The mixture was stirred at rt for 3 h. Progress of the reaction was monitored by TLC and LCMS. After completion, the reaction was quenched with sat. aq. sodium bicarbonate (200 mL) and then extracted with EtOAc (2 x 200 mL). The combined organic layers were washed with brine (1 x 75 mL), dried (Na ₂ SO ₄ ), filtered and evaporated to afford Intermediate 6-1 (22.0 g, crude) as a light-yellow sticky oil. The crude material was used for next step without further purification. MS (ESI) 459.3 [M+H] ⁺ . The absolute stereochemistry of Intermediate 6-1 was arbitrarily assigned. Intermediate 7 ^-1 5-(((tert-butyldiphenylsilyl)oxy)methyl)-1-methyl-1H-pyrazol e-3-carbaldehyde O ^TBDPS [0161] To a stirred solu enylsilyl)oxy)methyl)-1-methyl-1H- pyrazol-3-yl)methanol (20 g, 52.62 mmol) in DCM (200 mL) at 0 °C, was added DMP (26.7 g, 63.1 mmol). The mixture was stirred at rt for 16 h. The mixture was filtered through a Celite pad, and the Celite pad was washed with EtOAc (1 L). The filtrate was concentrated under reduced pressure, and the residue obtained was purified by flash chromatography (SiO2, 0-8% EtOAc:PE) to afford Intermediate 7-1 (12 g, 60%) as a colorless gummy liquid. MS (ESI) 380.45 [M+H] ⁺ . Intermediate 8-1 Methyl (R)-7-(4-(((5-(((tert-butyldiphenylsilyl)oxy)methyl)-1-methy l-1H-pyrazol-3- yl)methyl)amino)-2-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]p yridin-3-yl)-6-chloro-3-(3- methoxy-3-oxopropyl)-1-methyl-1H-indole-2-carboxylate [0162] To a stirre 17.7 mmol) and Intermediate 7-1 (4.6 g, 12.2 mmol) in DCE (80 mL) was added AcOH (1.0 mL). The mixture was stirred at rt for 5 h. Na(OAc) ₃ BH (7.2 g, 34.9 mmol) was added at 0 °C, and the mixture was stirred at rt for 16 h. Progress of the reaction was monitored by TLC and LCMS. After completion, the reaction was quenched with aqueous sodium bicarbonate (50 mL) and extracted with DCM (2 x 50 mL). The combined organic layers were washed with brine, dried (Na ₂ SO ₄ ), filtered and evaporated. The crude material was purified by flash chromatography (SiO2, 0-10% MeOH in DCM) to afford Intermediate 8-1 (6.0 g, 41%) as a light brown gummy oil. MS (ESI) 822.9 [M+H] ⁺ . The absolute stereochemistry of Intermediate 8-1 was arbitrarily assigned. Intermediate 9 ^-1 Methyl (R)-7-(4-(((5-(((tert-butyldiphenylsilyl)oxy)methyl)-1-methy l-1H-pyrazol-3- yl)methyl)(4-methoxybenzyl)amino)-2-methyl-4,5,6,7-tetrahydr opyrazolo[1,5-a]pyridin-3-yl)-6- chloro-3-(3-methoxy-3-oxopropyl)-1-methyl-1H-indole-2-carbox ylate [0163] To a stirred 0 g, 7.3 mmol) and ACN (60 mL) was added K2CO3 (3.0 g, 21.3 mmol) and TBAI (0.53 g, 1.46 mmol). The mixture was stirred at 0 °C for 10 min. PMB-Cl (1.7 g, 10.9 mmol) was added, and the mixture was stirred at 80 °C for 16 h. Progress of the reaction was monitored by TLC and LCMS. After completion, the reaction was quenched with water (40 mL) and extracted it with EtOAc (2 x 40 mL). The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated. The crude material was purified by flash chromatography (SiO ₂ , 0-10% MeOH in DCM) to afford Intermediate 9-1 (4.0 g, 58%). MS (ESI) 941.5 [M+H] ⁺ . The absolute stereochemistry of Intermediate 9-1 was arbitrarily assigned. Intermediate 10-1 Methyl (R)-6-chloro-7-(4-(((5-(hydroxymethyl)-1-methyl-1H-pyrazol-3 -yl)methyl)(4- methoxybenzyl)amino)-2-methyl-4,5,6,7-tetrahydropyrazolo[1,5 -a]pyridin-3-yl)-3-(3-methoxy- 3-oxopropyl)-1-methyl-1H-indole-2-carboxylate [0164] To a stirred s 4.0 g, 4.25 mmol) in THF (40 mL) was added TBAF (6.3 mL, 6.30 mmol) at 0 °C. The mixture was stirred at rt for 8 h. Progress of the reaction was monitored by TLC and LCMS. After completion, the reaction was quenched with water (30 mL) and extracted with EtOAc (2 x 20 mL). The combined organic layers were washed with brine, dried (Na ₂ SO ₄ ), filtered and evaporated. The crude material was purified by flash chromatography (SiO ₂ , 0-80% EtOAc:PE) to afford Intermediate 10-1 (2.7 g, 90%). MS (ESI) 703.6 [M+H] ⁺ . The absolute stereochemistry of Intermediate 10-1 was arbitrarily assigned.

Intermediate 11-1 Methyl (R)-6-chloro-7-(4-(((5-(chloromethyl)-1-methyl-1H-pyrazol-3- yl)methyl)(4- methoxybenzyl)amino)-2-methyl-4,5,6,7-tetrahydropyrazolo[1,5 -a]pyridin-3-yl)-3-(3-methoxy- 3-oxopropyl)-1-methyl-1H-indole-2-carboxylate [0165] To a stirred (2.7 g, 3.84 mmol) in DCM (27.0 mL) was added SOCl ₂ (0.41 mL, 5.76 mmol) at 0 °C. The mixture was stirred at rt for 2 h. Progress of the reaction was monitored by TLC and LCMS. After completion, the reaction was quenched with saturated sodium bicarbonate (30 mL) and extracted with DCM (2 x 20 mL). The organic layer was separated, dried over Na ₂ SO ₄ , filtered, and evaporated to afford Intermediate 11-1 (2.8 g, crude) as a light-yellow oil, which was used for next step without purification. MS (ESI) 722.7 [M+H] ⁺ . The absolute stereochemistry of Intermediate 11-1 was arbitrarily assigned. Intermediate 12-1 Methyl (R)-7-(4-(((5-((acetylthio)methyl)-1-methyl-1H-pyrazol-3-yl) methyl)(4- methoxybenzyl)amino)-2-methyl-4,5,6,7-tetrahydropyrazolo[1,5 -a]pyridin-3-yl)-6-chloro-3-(3- methoxy-3-oxopropyl)-1-methyl-1H-indole-2-carboxylate [0166] To a stirred s 2.8 g, 3.88 mmol) in ACN (28 mL) was added AcSK ( 0.88 g, 7.77 mmol) and KI (0.645 g 3.88 mmol) at 0 °C. The mixture was stirred at rt for 16 h. Progress of the reaction was monitored by TLC and LCMS. After completion, the reaction was quenched with water (30 mL) and extracted with EtOAc (2 x 30 mL). The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated. The crude material was purified by flash chromatography (SiO ₂ , 0-70% EtOAc:PE) to afford Intermediate 12-1 (2.0 g, 68%) as a light brown oil. MS (ESI) 762.3 [M+H] ⁺ . The absolute stereochemistry of Intermediate 12-1 was arbitrarily assigned. Intermediate 13-1 Methyl (R)-6-chloro-7-(4-(((5-(((7-fluoro-4-hydroxynaphthalen-2-yl) thio)methyl)-1-methyl-1H- pyrazol-3-yl)methyl)(4-methoxybenzyl)amino)-2-methyl-4,5,6,7 -tetrahydropyrazolo[1,5- a]pyridin-3-yl)-3-(3-methoxy-3-oxopropyl)-1-methyl-1H-indole -2-carboxylate [0167] A stirred so (2.0 g, 2.63 mmol) and 4-((tert- butyldimethylsilyl)oxy)-7-fluoronaphthalen-2-yl trifluoromethanesulfonate (1.1 g, 2.63 mmol) in 1,4 dioxane (18 mL) and water (2 mL) was purged with argon for 10 min. Pd ₂ dba ₃ (0.120 g, 0.13 mmol), Xphos (0.125 g, 0.26 mmol) and K2CO3 (0.544 g, 3.94 mmol) were added at rt. The mixture was stirred at 100 °C for 16 h. Progress of the reaction was monitored by TLC and LCMS. After completion, the mixture was cooled to rt, and the reaction was quenched with ice cold water (30 mL) and extracted with EtOAc (2 x 30 mL). The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated. The crude material was purified by flash chromatography (SiO ₂ , 0-70% EtOAc:PE) to afford Intermediate 13-1 (1.6 g, 69%). MS (ESI) 879.5 [M+H] ⁺ . The absolute stereochemistry of Intermediate 13-1 was arbitrarily assigned. Intermediate 14 ^-1 Methyl (R)-6-chloro-7-(4-(((5-(((7-fluoro-4-hydroxynaphthalen-2-yl) thio)methyl)-1-methyl-1H- pyrazol-3-yl)methyl)(4-methoxybenzyl)amino)-2-methyl-4,5,6,7 -tetrahydropyrazolo[1,5- a]pyridin-3-yl)-3-(3-hydroxypropyl)-1-methyl-1H-indole-2-car boxylate [0168] To a stirred s (1.6 g, 1.82 mmol) in THF (18 mL) was added BH ₃ •THF (10.0 g, 10.0 mmol, 1.0 M in THF) dropwise at 0 °C. The mixture was stirred at rt for 16 h. Progress of the reaction was monitored by TLC and LCMS. After completion, the reaction was quenched with MeOH (5 mL) and 6.0 N HCl (5 mL) diluted with water (20 mL), and then extracted with EtOAc (2 x 30 mL). The combined organic layers were washed with brine, dried (Na ₂ SO ₄ ), filtered and evaporated. The crude material was purified by flash chromatography (SiO2, 0-70% EtOAc:PE) to afford Intermediate 14-1 (700 mg, 43%). MS (ESI) 851.5 [M+H] ⁺ . The absolute stereochemistry of Intermediate 14-1 was arbitrarily assigned. Intermediate 15-1 Methyl (R,Z)-1 ⁶ -chloro-8 ⁶ -fluoro-3-(4-methoxybenzyl)-1 ¹ ,2 ² ,5 ¹ -trimethyl-2 ⁴ ,2 ⁵ ,2 ⁶ ,2 ⁷ -tetrahydro- 1 ¹ H,5 ¹ H-9-oxa-7-thia-3-aza-2(3,4)-pyrazolo[1,5-a]pyridina-1( 7,3)-indola-5(3,5)-pyrazola-8(3,1)- naphthalenacyclododecaphane- 1 ² -carboxylate [0169] A solutio 7 mmol) in DCM (10 mL) was degassed with argon for 10 min. Di-tert-butyl (E)-diazene-1,2-dicarboxylate (0.676 mg, 2.94 mmol) and TPP (0.770 mg, 2.94mmol) were added at rt. The mixture was stirred at rt for 2 h. Progress of the reaction was monitored by TLC and LCMS. After completion, the reaction was quenched with water (20 mL) and extracted with EtOAc (2 x 20 mL). The combined organic layers were washed with brine, dried (Na2SO4), filtered, and evaporated. The crude material was purified by flash chromatography (SiO ₂ , 0-70% EtOAc:PE) to afford Intermediate 15-1 (180 mg, 18%). MS (ESI) 833.4 [M+H] ⁺ . The absolute stereochemistry of Intermediate 15-1 was arbitrarily assigned. Intermediate 16A-1 Methyl (R,Z)-1 ⁶ -chloro-8 ⁶ -fluoro-1 ¹ ,2 ² ,5 ¹ -trimethyl-2 ⁴ ,2 ⁵ ,2 ⁶ ,2 ⁷ -tetrahydro-1 ¹ H,5 ¹ H-9-oxa-7-thia- 3-aza-2(3,4)-pyrazolo[1,5-a]pyridina-1(7,3)-indola-5(3,5)-py razola-8(3,1)- naphthalenacyclododecaphane-1 ² -carboxylate Intermediate 16B ^-1 Methyl (R,Z)-1 ⁶ -chloro-8 ⁶ -fluoro-1 ¹ ,2 ² ,5 ¹ -trimethyl-2 ⁴ ,2 ⁵ ,2 ⁶ ,2 ⁷ -tetrahydro-1 ¹ H,5 ¹ H-9-oxa-7-thia- 3-aza-2(3,4)-pyrazolo[1,5-a]pyridina-1(7,3)-indola-5(3,5)-py razola-8(3,1)- naphthalenacyclododecaphane-1 ² -carboxylate [0170] To a stirre 80 mg, 0.216 mmol) in TFA (4 mL) was added anisole (1 mL) at rt. The mixture was stirred at 80 °C for 16 h. Progress of the reaction was monitored by TLC and LCMS. After completion, the reaction was quenched with aqueous sodium bicarbonate solution (15 mL) and extracted with EtOAc (2 x 10 mL). The combined organic layers were washed with brine, dried (Na ₂ SO ₄ ), filtered and evaporated. The crude material was purified by flash chromatography (SiO2, 0-70% EtOAc:PE) to afford racemic methyl (R,Z)-1 ⁶ -chloro-8 ⁶ -fluoro-1 ¹ ,2 ² ,5 ¹ -trimethyl-2 ⁴ ,2 ⁵ ,2 ⁶ ,2 ⁷ -tetrahydro-1 ¹ H,5 ¹ H-9-oxa-7-thia- 3-aza-2(3,4)-pyrazolo[1,5-a]pyridina-1(7,3)-indola-5(3,5)-py razola-8(3,1)- naphthalenacyclododecaphane-1 ² -carboxylate (120 mg, 75%). MS (ESI) 713.3 [M+H] ⁺ . [0171] The atropisomers were separated by chiral SFC chromatography (Chiralpak- IA(30 x 250 mm), 5µ 40% MeOH : ACN, 1:1) to give peak 1 (Intermediate 16A-1, 18 mg) and peak 2 (Intermediate 16B-1, 60 mg). Intermediate 16A-1: 97.7% chiral purity; MS (ESI) 713.3 [M+H] ⁺ . Intermediate 16B-1: 99.8% chiral purity; MS (ESI) 713.3 [M+H] ⁺ . The absolute stereochemistry of Intermediate 16A-1 and Intermediate 16B-1 was arbitrarily assigned. Example 1A-1 (R,Z)-1 ⁶ -chloro-8 ⁶ -fluoro-1 ¹ ,2 ² ,5 ¹ -trimethyl-2 ⁴ ,2 ⁵ ,2 ⁶ ,2 ⁷ -tetrahydro-1 ¹ H,5 ¹ H-9-oxa-7-thia-3-aza- 2(3,4)-pyrazolo[1,5-a]pyridina-1(7,3)-indola-5(3,5)-pyrazola -8(3,1)- naphthalenacyclododecaphane-1 ² -carboxylic acid [0172] To a stirr A-1 (16 mg, 0.022 mmol) in MeOH:THF:H ₂ O (1:1:1, 3 mL) was added LiOH•H ₂ O (8.0 mg, 0.33 mmol) at rt, and the mixture was stirred at 70 °C for 2 h. Progress of the reaction was monitored by TLC and LCMS. After completion, the mixture was evaporated under reduced pressure, and the crude was acidified to pH 2 using 2.0 N aqueous HCl. An off-white precipitate was formed. The mixture was filtered, and the product was washed with ice cold water and dried in vacuum to afford Example 1A-1 (9.0 mg, 60%, 98.8% chiral purity). ¹ H NMR (400 MHz, DMSO-d6) δ 13.36 (bs,1H), 9.10 (bs, 1H), 8.06 (t, J = 7.2 Hz, 1H), 8.00 (d = 8.8 Hz, 1H), 7.47 (t, J = 5.6 Hz, 1H), 7.28-7.24 (m, 3H), 6.80 (bs, 1H), 4.39-3.47 (m, 15H), 3.13-3.03 (m, 2H), 2.49-2.48 (m, 1H), 2.33-1.40 (m, 9H). MS (ESI) 697.38 [M-H]-. Example 1B-1 (R,Z)-1 ⁶ -chloro-8 ⁶ -fluoro-1 ¹ ,2 ² ,5 ¹ -trimethyl-2 ⁴ ,2 ⁵ ,2 ⁶ ,2 ⁷ -tetrahydro-1 ¹ H,5 ¹ H-9-oxa-7-thia-3-aza- 2(3,4)-pyrazolo[1,5-a]pyridina-1(7,3)-indola-5(3,5)-pyrazola -8(3,1)- naphthalenacyclododecaphane-1 ² -carboxylic acid [0173] To a stir 6B-1 (60 mg,0.084 mmol) in MeOH:THF:H2O (1:1:1, 3 mL) was added LiOH•H2O (30 mg,1.26 mmol) at rt. and the mixture was stirred at 70 °C for 2 h. Progress of the reaction was monitored by TLC and LCMS. After completion, the mixture was evaporated under reduced pressure, and the crude was acidified to pH 2 using 2.0 N aqueous HCl. An off-white precipitate was formed. The mixture was filtered, and the product was washed with ice cold water and dried in vacuum to obtain Example 1B-1 (24 mg, 41%, 99.9% chiral purity). ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.13 - 8.09 (m, 1H), 7.77 (d, J = 8.4 Hz, 1H), 7.50-7.47 (dd, J 0.4, 2.4 Hz, 1H), 7.33-7.27 (m, 2H), 7.07 (d, J = 8.8 Hz, 1H), 6.84 (s, 1H), 4.80 (s, 1H), 4.45-4.30 (m, 3H), 4.05-4.0 (m, 2H), 3.83-3.79 (m, 1H), 3.71 (s, 3H), 3.70-3.67 (m, 2H), 3.53-3.50 (m, 1H), 3.40 (s, 3H), 3.21-3.18 (m, 1H), 2.91-2.84 (m, 2H), 2.33 (bs, 1H), 2.18-2.07 (m, 2H),1.93 (m, 4H), 1.91 (bs, 1H), 1.58 (bs, 1H). MS (ESI) 699.4 [M+H] ⁺ . [0174] As provided herein, both atropisomers, Example 1A-1 and Example 1B-1, were obtained. The absolute stereochemistry of Example 1A-1 and Example 1B-1 was arbitrarily assigned. Intermediate 17-1 4-bromo-5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole-3- carbaldehyde [0175] (4-Bromo-5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3- yl)methanol (5.33 g, 19.37 mmol, WO 2020/254471A1) was dissolved in DCM (10 mL) and DMSO (10 mL). Triethylamine (10.80 mL, 77.0 mmol) was added followed by a sulfur trioxide pyridine complex (6.17 g, 38.7 mmol). The reaction was stirred for 2 h. The reaction was monitored by LCMS and TLC. The mixture was poured into a mixture of EtOAc (50 mL) and ether (50 mL). The mixture was washed with water (2 x 100 mL) and brine (100 mL). The combined organic layers were washed with brine, dried (Na ₂ SO ₄ ), filtered and evaporated. The crude material was purified by flash chromatography (SiO2, 0-50% EtOAc:PE) to afford Intermediate 17-1 (3.87 g, 73%). MS (ESI) 273.1 [M+H] ⁺ . Intermediate 18-1 1-(4-bromo-5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol- 3-yl)prop-2-en-1-ol [0176] To a solution of Inte -1 (3.87 g, 14.17 mmol) in dry THF (10 mL) at -5 °C was added vinylmagnesium bromide (14.88 ml, 14.88 mmol) drop wise via a syringe. The reaction was complete by TLC in 1 h. The reaction was quenched with sat. NH4Cl (10 mL) followed by the addition of water (10 mL). The mixture was extracted with EtOAc (3 x 50 mL). The combined organic layers were washed with brine (1 x 100 mL) and dried (Na ₂ SO ₄ ). The solvent was removed, and the residue was purified by column chromatography (SiO2, 0-40% EtOAc:PE) to afford Intermediate 18-1 (2.77 g, 64%) as an oil. MS (ESI) 300.2 [M+H] ⁺ . Intermediate 19-1 1-(4-bromo-5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol- 3-yl)prop-2-en-1-one [0177] To a solution of Inter 1 (2.70 g, 8.96 mmol) 1,4-dioxane (16 mL) was added manganese(IV) oxide (3.90 g, 44.8 mmol). The mixture was stirred overnight at rt. A second portion of manganese(IV) oxide (3.90 g, 44.8 mmol) was added, and the mixture was stirred for 4 h at 40 ^o C. The mixture was filtered through Celite, and the solvent was removed. The residue obtained was purified by column chromatography (SiO2, 0-40% EtOAc:PE) to afford Intermediate 19-1 (1.15 g, 42%). MS (ESI) 299.1 [M+H] ⁺ . Intermediate 20 ^-1 3-bromo-1-(4-bromo-5-methyl-1H-pyrazol-3-yl)propan-1-one hydrobromide [0178] To a solution of Int 19-1 (1.10 g, 3.68 mmol) in DCM (10 mL) at 0 ^o C was added 33 % hydrogen bromide in acetic acid (2.00 mL, 11.03 mmol). DCM (2 mL) was added with stirring. The mixture was stirred for 30 min. The reaction was monitored by LCMS. The ice bath was removed and heptane (15 mL) was added. The mixture was stirred for 10 min and then filtered. The obtained compound was dried by high vacuum to afford Intermediate 20- 1 (1.36 g, 98%). MS (ESI) 293.9 [M+H] ⁺ . Intermediate 21-1 3-bromo-2-methyl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-4-one [0179] A suspension of Cs ₂ C 1.59 mmol) in CH ₃ CN (5.1 mL) was heated to reflux. Intermediate 20-1 (0.200 g, 0.531 mmol) was added to the mixture in portions over 2 min. The reaction was completed by LCMS in 5 min. The mixture was cooled to rt and EtOAc (10 mL) was added. The mixture was filtered through Celite, and filtrate was washed with sat. NH4Cl (50 uL). The organic layer was separated and evaporated. The crude material was purified by flash chromatography (SiO2, 0-50% EtOAc:PE) to afford Intermediate 21-1 (92 mg, 81%). MS (ESI) 213.9 [M+H] ⁺ . Intermediate 22-1 (R,E)-N-(3-bromo-2-methyl-5,6-dihydro-4H-pyrrolo[1,2-b]pyraz ol-4-ylidene)-2-methylpropane- 2-sulfinamide [0180] Intermediate 22- from Intermediate 21-1 following a procedure from the preparation of Intermediate 1-1. MS (LCMS) 318.02 [M+H] ⁺ . Intermediate 23 ^-1 (R)-N-((R)-3-bromo-2-methyl-5,6-dihydro-4H-pyrrolo[1,2-b]pyr azol-4-yl)-2-methylpropane-2- sulfinamide [0181] Intermediate 23-1 rom Intermediate 22-1 by following the procedure for the preparation of Intermediate 2-1. MS (LCMS) 318.02 [M+H] ⁺ . The absolute stereochemistry of Intermediate 23-1 was arbitrarily assigned. Intermediate 24-1 Methyl 7-((R)-4-(((R)-tert-butylsulfinyl)amino)-2-methyl-5,6-dihydr o-4H-pyrrolo[1,2-b]pyrazol- 3-yl)-6-chloro-3-(3-methoxy-3-oxopropyl)-1H-indole-2-carboxy late [0182] Intermediate ntermediate 3-1 and Intermediate 23-1 by following the procedure for the preparation of Intermediate 4-1. MS (LCMS) 535.4 [M+H] ⁺ . The absolute stereochemistry of Intermediate 24-1 was arbitrarily assigned. Intermediate 25-1 Methyl 7-((R)-4-(((R)-tert-butylsulfinyl)amino)-2-methyl-5,6-dihydr o-4H-pyrrolo[1,2-b]pyrazol- 3-yl)-6-chloro-3-(3-methoxy-3-oxopropyl)-1-methyl-1H-indole- 2-carboxylate [0183] Intermediate Intermediate 24-1 by following the procedure for the preparation of Intermediate 5-1. MS (LCMS) 549.3 [M+H] ⁺ . The absolute stereochemistry of Intermediate 25-1 was arbitrarily assigned. Intermediate 26-1 Methyl (R)-7-(4-amino-2-methyl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol -3-yl)-6-chloro-3-(3- methoxy-3-oxopropyl)-1-methyl-1H-indole-2-carboxylate [0184] Intermediate 2 Intermediate 25-1 by following the procedure for the preparation of Intermediate 6-1. MS (LCMS) 445.2 [M+H] ⁺ . The absolute stereochemistry of Intermediate 26-1 was arbitrarily assigned. Intermediate 27 ^-1 Methyl (R)-7-(4-(((5-(((tert-butyldiphenylsilyl)oxy)methyl)-1-methy l-1H-pyrazol-3- yl)methyl)amino)-2-methyl-5,6-dihydro-4H-pyrrolo[1,2-b]pyraz ol-3-yl)-6-chloro-3-(3-methoxy- 3-oxopropyl)-1-methyl-1H-indole-2-carboxylate [0185] Intermediate 27-1 was synthesized from Intermediate 26-1 and Intermediate 7-1 by following the procedure for the preparation of Intermediate 8-1. MS (LCMS) 808.9 [M+H] ⁺ . The absolute stereochemistry of Intermediate 27-1 was arbitrarily assigned. Intermediate 28-1 Methyl (R)-7-(4-(((5-(((tert-butyldiphenylsilyl)oxy)methyl)-1-methy l-1H-pyrazol-3- yl)methyl)(4-methoxybenzyl)amino)-2-methyl-5,6-dihydro-4H-py rrolo[1,2-b]pyrazol-3-yl)-6- chloro-3-(3-methoxy-3-oxopropyl)-1-methyl-1H-indole-2-carbox ylate [0186] Intermediat ntermediate 27-1 by following the procedure for the preparation of Intermediate 9-1. MS (LCMS) 927.9 [M+H] ⁺ . The absolute stereochemistry of Intermediate 28-1 was arbitrarily assigned. Intermediate 29 ^-1 Methyl (R)-6-chloro-7-(4-(((5-(hydroxymethyl)-1-methyl-1H-pyrazol-3 -yl)methyl)(4- methoxybenzyl)amino)-2-methyl-5,6-dihydro-4H-pyrrolo[1,2-b]p yrazol-3-yl)-3-(3-methoxy-3- oxopropyl)-1-methyl-1H-indole-2-carboxylate [0187] Intermediate Intermediate 28-1 by following the procedure for the preparation of Intermediate 10-1. MS (LCMS) 689.8 [M+H] ⁺ . The absolute stereochemistry of Intermediate 29-1 was arbitrarily assigned. Intermediate 30-1 Methyl (R)-6-chloro-7-(4-(((5-(chloromethyl)-1-methyl-1H-pyrazol-3- yl)methyl)(4- methoxybenzyl)amino)-2-methyl-5,6-dihydro-4H-pyrrolo[1,2-b]p yrazol-3-yl)-3-(3-methoxy-3- oxopropyl)-1-methyl-1H-indole-2-carboxylate [0188] Intermediate Intermediate 29-1 by following the procedure for the preparation of Intermediate 11-1. MS (LCMS) 707.4 [M+H] ⁺ . The absolute stereochemistry of Intermediate 30-1 was arbitrarily assigned. Intermediate 31-1 Methyl (R)-7-(4-(((5-((acetylthio)methyl)-1-methyl-1H-pyrazol-3-yl) methyl)(4- methoxybenzyl)amino)-2-methyl-5,6-dihydro-4H-pyrrolo[1,2-b]p yrazol-3-yl)-6-chloro-3-(3- methoxy-3-oxopropyl)-1-methyl-1H-indole-2-carboxylate [0189] Intermediate Intermediate 30-1 by following the procedure for the preparation of Intermediate 12-1. MS (LCMS) 747.6 [M+H] ⁺ . The absolute stereochemistry of Intermediate 31-1 was arbitrarily assigned.

Intermediate 32-1 Methyl (R)-6-chloro-7-(4-(((5-(((7-fluoro-4-hydroxynaphthalen-2-yl) thio)methyl)-1-methyl-1H- pyrazol-3-yl)methyl)(4-methoxybenzyl)amino)-2-methyl-5,6-dih ydro-4H-pyrrolo[1,2-b]pyrazol- 3-yl)-3-(3-methoxy-3-oxopropyl)-1-methyl-1H-indole-2-carboxy late [0190] Intermediate ntermediate 31-1 by following the procedure for the preparation of Intermediate 13-1. MS (LCMS) 865.8 [M+H] ⁺ . The absolute stereochemistry of Intermediate 32-1 was arbitrarily assigned. Intermediate 33-1 Methyl (R)-6-chloro-7-(4-(((5-(((7-fluoro-4-hydroxynaphthalen-2-yl) thio)methyl)-1-methyl-1H- pyrazol-3-yl)methyl)(4-methoxybenzyl)amino)-2-methyl-5,6-dih ydro-4H-pyrrolo[1,2-b]pyrazol- 3-yl)-3-(3-hydroxypropyl)-1-methyl-1H-indole-2-carboxylate [0191] Intermediate ntermediate 32-1 by following the procedure for the preparation of Intermediate 14-1. MS (LCMS) 837.3 [M+H] ⁺ . The absolute stereochemistry of Intermediate 33-1 was arbitrarily assigned. Intermediate 34-1 Methyl (R,Z)-1 ⁶ -chloro-8 ⁶ -fluoro-3-(4-methoxybenzyl)-1 ¹ ,2 ² ,5 ¹ -trimethyl-2 ⁵ ,2 ⁶ -dihydro- 1 ¹ H,2 ⁴ H,5 ¹ H-9-oxa-7-thia-3-aza-1(7,3)-indola-2(3,4)-pyrrolo[1,2- b]pyrazola-5(3,5)-pyrazola- 8(3,1)-naphthalenacyclododecaphane-1 ² -carboxylate [0192] Intermedi rmediate 33-1 by following the procedure for the preparation of Intermediate 15-1. MS (LCMS) 819.37 [M+H] ⁺ . The absolute stereochemistry of Intermediate 34-1 was arbitrarily assigned. Intermediate 35A-1 Methyl (R,Z)-1 ⁶ -chloro-8 ⁶ -fluoro-1 ¹ ,2 ² ,5 ¹ -trimethyl-2 ⁵ ,2 ⁶ -dihydro-1 ¹ H,2 ⁴ H,5 ¹ H-9-oxa-7-thia-3- aza-1(7,3)-indola-2(3,4)-pyrrolo[1,2-b]pyrazola-5(3,5)-pyraz ola-8(3,1)- naphthalenacyclododecaphane-1 ² -carboxylate

Intermediate 35B-1 Methyl (R,Z)-1 ⁶ -chloro-8 ⁶ -fluoro-1 ¹ ,2 ² ,5 ¹ -trimethyl-2 ⁵ ,2 ⁶ -dihydro-1 ¹ H,2 ⁴ H,5 ¹ H-9-oxa-7-thia-3- aza-1(7,3)-indola-2(3,4)-pyrrolo[1,2-b]pyrazola-5(3,5)-pyraz ola-8(3,1)- naphthalenacyclododecaphane-1 ² -carboxylate [0193] To a stirred mg, 0.085 mmol) in anisole (0.01 mL) was added TFA (0.1 mL) dropwise at 0 °C. The mixture was stirred at 80 °C for 16 h. Progress of reaction was monitored by TLC and LCMS. After completion, the reaction was quenched with sat. aq. NaHCO ₃ solution (10 mL) at 0 °C and then extracted with DCM (2 x 10 mL). The combined organic layers were separated, dried (Na2SO4), filtered and evaporated. The crude material was purified by flash chromatography (SiO ₂ , 0-80% EtOAc:PE) to afford racemic methyl (R,Z)-1 ⁶ -chloro-8 ⁶ -fluoro-1 ¹ ,2 ² ,5 ¹ -trimethyl-2 ⁵ ,2 ⁶ -dihydro-1 ¹ H,2 ⁴ H,5 ¹ H-9-oxa-7-thia-3- aza-1(7,3)-indola-2(3,4)-pyrrolo[1,2-b]pyrazola-5(3,5)-pyraz ola-8(3,1)- naphthalenacyclododecaphane-1 ² -carboxylate (55 mg, 93%). MS (ESI) 699.3 [M+H] ⁺ . [0194] The atropisomers were separated by chiral SFC chromatography (Chiralpak-IG (25 x 250)mm, 5µ, 50% CH ₃ CN:MeOH; 1:1) to give peak 1 (Intermediate 35A-1, 50 mg) and peak 2 (Intermediate 35B-1, 50 mg). Intermediate 35A-1: 99.6% chiral purity; MS (ESI) 699.3 [M+H] ⁺ . Intermediate 35B-1: 97.2% chiral purity; MS (ESI) 722.5 [M+H] ⁺ . The absolute stereochemistry of Intermediate 35A-1 and Intermediate 35B-1 was arbitrarily assigned.

Example 2A-1 (R,Z)-1 ⁶ -chloro-8 ⁶ -fluoro-1 ¹ ,2 ² ,5 ¹ -trimethyl-2 ⁵ ,2 ⁶ -dihydro-1 ¹ H,2 ⁴ H,5 ¹ H-9-oxa-7-thia-3-aza- 1(7,3)-indola-2(3,4)-pyrrolo[1,2-b]pyrazola-5(3,5)-pyrazola- 8(3,1)- naphthalenacyclododecaphane-1 ² -carboxylic acid [0195] To a stirr A-1 (15 mg, 0.021 mmol) in MeOH:THF:H2O (1:1:1 mL) was added LiOH•H2O (8 mg, 0.34 mmol) at rt, and the mixture was stirred at 70 °C for 2 h. Progress of reaction was monitored by TLC and LCMS. After completion, the solvent was evaporated. The aqueous layer was acidified to pH 2 using 2 N aqueous HCl. The precipitate was filtered off and washed with water (10 mL). The product was collected and dried under vacuum to afford Example 2A-1 (6.5 mg, 44%, 97.9% chiral purity). ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 13.30 (brs, 1H), 9.80 (brs, 1H), 8.12-8.08 (m, 1H), 7.91 (d, J = 8.8 Hz, 1H), 7.53- 7.50 (dd, J = 10, 2.4 Hz, 1H), 7.39 (s, 1H), 7.33 (t, J = 2.4 Hz, 1H), 7.20 (d, J = 8.8 Hz, 1H), 6.51 (s, 1H), 4.73 (s, 1H), 4.38-4.00 (m, 6H), 3.78-3.65 (m, 7H), 3.48-3.41 (m, 2H), 3.14-3.09 (m, 4H), 2.37 (bs, 2H), 1.93 (s, 3H). MS (ESI) 683.2 [M-H]-. Example 2B ^-1 (R,Z)-1 ⁶ -chloro-8 ⁶ -fluoro-1 ¹ ,2 ² ,5 ¹ -trimethyl-2 ⁵ ,2 ⁶ -dihydro-1 ¹ H,2 ⁴ H,5 ¹ H-9-oxa-7-thia-3-aza- 1(7,3)-indola-2(3,4)-pyrrolo[1,2-b]pyrazola-5(3,5)-pyrazola- 8(3,1)- naphthalenacyclododecaphane-1 ² -carboxylic acid [0196] To a stirred solution of Intermediate 35B-1 (15 mg, 0.021 mmol) in MeOH:THF:H2O (1:1:1 mL) was added LiOH•H2O (8 mg, 0.34 mmol) at rt, and the mixture was stirred at 70 °C for 2 h. Progress of reaction was monitored by TLC and LCMS. After completion, the solvent was evaporated. The aqueous layer was acidified to pH 2 using 2 N aqueous HCl. The product was filtered off and washed with water (10 mL). The product was collected and dried under vacuum to afford Example 2B-1 (6.5 mg, 44%, 99.7% chiral purity). ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 13.30 (brs, 1H), 9.40 (bs, 1H), 8.35 (s, 1H), 7.59-7.40 (m, 4H), 6.79 (bs, 1H), 6.57 (s, 1H), 6.51 (s, 1H), 5.44 (bs, 1H), 4.61-4.11 (m, 6H), 3.71 (s, 3H), 3.49-3.46 (m, 5H), 3.25 (bs, 1H), 3.12-2.82 (m, 3H), 2.39 (bs, 1H), 2.11-2.08 (m, 4H). MS (ESI) 683.2 [M-H]-. [0197] As provided herein, both atropisomers, Example 2A-1 and Example 2B-1, were obtained. The absolute stereochemistry of Example 2A-1 and Example 2B-1 was arbitrarily assigned. Intermediate 36-1 methyl (R)-7-(4-(((5-(((tert-butyldiphenylsilyl)oxy)methyl)-1-methy l-1H-pyrazol-3- yl)methyl)(methyl)amino)-2-methyl-4,5,6,7-tetrahydropyrazolo [1,5-a]pyridin-3-yl)-6-chloro-3- (3-methoxy-3-oxopropyl)-1-methyl-1H-indole-2-carboxylate [0198] To a stirred 8.0 g, 9.75 mmol) in MeOH (90.0 mL) at 0 °C, aq. formaldehyde (3.0 g 24.4 mmol) and acetic acid (1.2 mL, catalytic) were added. The mixture was stirred at 0 °C for 30 min. NaCNBH ₃ (1.53 g, 24.37 mmol) was added, and the mixture was stirred at 80 °C for 16 h. After completion of reaction, the reaction was quenched water (100.0 mL) and extracted with EtOAc (2 x 200 mL). The mixture was poured into a mixture of EtOAc (50 mL) and ether (50 mL). The mixture was washed with water (2 x 100 mL) and brine (100 mL). The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated. The crude material was purified by flash chromatography (SiO2, 0-80% EtOAc:PE) to afford Intermediate 36-1 (6.0 g, 74%). The absolute stereochemistry of Intermediate 36-1 was arbitrarily assigned. Intermediate 37-1 Methyl (R)-6-chloro-7-(4-(((5-(hydroxymethyl)-1-methyl-1H-pyrazol-3 - yl)methyl)(methyl)amino)-2-methyl-4,5,6,7-tetrahydropyrazolo [1,5-a]pyridin-3-yl)-3-(3- methoxy-3-oxopropyl)-1-methyl-1H-indole-2-carboxylate [0199] Intermediat ntermediate 36-1 by following the procedure for the preparation of Intermediate 10-1. MS (ESI) 597.5 [M+H] ⁺ . The absolute stereochemistry of Intermediate 37-1 was arbitrarily assigned. Intermediate 38 ^-1 Methyl (R)-6-chloro-7-(4-(((5-(chloromethyl)-1-methyl-1H-pyrazol-3- yl)methyl)(methyl)amino)-2-methyl-4,5,6,7-tetrahydropyrazolo [1,5-a]pyridin-3-yl)-3-(3- methoxy-3-oxopropyl)-1-methyl-1H-indole-2-carboxylate [0200] Intermediat ntermediate 37-1 by following the procedure for the preparation of Intermediate 11-1. MS (ESI) 615.5 [M+H] ⁺ . The absolute stereochemistry of Intermediate 38-1 was arbitrarily assigned. Intermediate 39-1 Methyl (R)-7-(4-(((5-((acetylthio)methyl)-1-methyl-1H-pyrazol-3-yl) methyl)(methyl)amino)-2- methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)-6-chlo ro-3-(3-methoxy-3-oxopropyl)-1- methyl-1H-indole-2-carboxylate [0201] Intermediat ntermediate 38-1 by following the procedure for the preparation of Intermediate 12-1. MS (ESI) 656.33 [M+H] ⁺ . The absolute stereochemistry of Intermediate 39-1 was arbitrarily assigned. Intermediate 40 ^-1 Methyl (R)-6-chloro-7-(4-(((5-(((7-fluoro-4-hydroxynaphthalen-2-yl) thio)methyl)-1-methyl-1H- pyrazol-3-yl)methyl)(methyl)amino)-2-methyl-4,5,6,7-tetrahyd ropyrazolo[1,5-a]pyridin-3-yl)-3- (3-methoxy-3-oxopropyl)-1-methyl-1H-indole-2-carboxylate [0202] Intermediat ntermediate 39-1 by following the procedure for the preparation of Intermediate 13-1. MS (ESI) 773.7 [M+H] ⁺ . The absolute stereochemistry of Intermediate 40-1 was arbitrarily assigned. Intermediate 41-1 Methyl (R)-6-chloro-7-(4-(((5-(((7-fluoro-4-hydroxynaphthalen-2-yl) thio)methyl)-1-methyl-1H- pyrazol-3-yl)methyl)(methyl)amino)-2-methyl-4,5,6,7-tetrahyd ropyrazolo[1,5-a]pyridin-3-yl)-3- (3-hydroxypropyl)-1-methyl-1H-indole-2-carboxylate [0203] Intermediat ntermediate 40-1 by following the procedure for the preparation of Intermediate 14-1. MS (ESI) 745.73 [M+H] ⁺ . The absolute stereochemistry of Intermediate 41-1 was arbitrarily assigned. Intermediate 42A-1 Methyl (R,Z)-1 ⁶ -chloro-8 ⁶ -fluoro-1 ¹ ,2 ² ,5 ¹ ,3- tetramethyl -2 ⁴ ,2 ⁵ ,2 ⁶ ,2 ⁷ -tetrahydro-1 ¹ H,5 ¹ H-9-oxa- 7-thia-3-aza-2(3,4)-pyrazolo[1,5-a]pyridina-1(7,3)-indola-5( 3,5)-pyrazola-8(3,1)- naphthalenacyclododecaphane-1 ² -carboxylate Intermediate 42B-1 Methyl (R,Z)-1 ⁶ -chloro-8 ⁶ -fluoro-1 ¹ ,2 ² ,5 ¹ ,3- tetramethyl -2 ⁴ ,2 ⁵ ,2 ⁶ ,2 ⁷ -tetrahydro-1 ¹ H,5 ¹ H-9-oxa- 7-thia-3-aza-2(3,4)-pyrazolo[1,5-a]pyridina-1(7,3)-indola-5( 3,5)-pyrazola-8(3,1)- naphthalenacyclododecaphane-1 ² -carboxylate [0204] A solution mmol) in DCM (10.0 mL) was degassed with Argon for 10 min. TPP (1.32 g, 5.0 mmol) was added. A solution of Di-tert-butyl (E)-diazene-1,2-dicarboxylate (1.15 g, 5.0 mmol) in DCM (5 mL) were also added dropwise, and the mixture was stirred at rt for 2 h. After completion of reaction, the reaction was quenched with water (20.0 mL) and extracted with DCM (2 x 50 mL). The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated. The crude material was purified by flash chromatography (SiO ₂ , 0-70% EtOAc:PE) to afford racemic methyl (R,Z)-16-chloro-86-fluoro- 11,22,51,3-tetramethyl-24,25,26,27-tetrahydro-11H,51H-9-oxa- 7-thia-3-aza-2(3,4)-pyrazolo[1,5- a]pyridina-1(7,3)-indola-5(3,5)-pyrazola-8(3,1)-naphthalenac yclododecaphane-12-carboxylate (550 mg, 36%). MS (ESI) 727.58 [M+H] ⁺ . [0205] The atropisomers were separated by chiral SFC chromatography (Chiralpak-IA (30 x 250) mm, 5µ, 40% acetonitrile : MeOH, 1:1) to give peak 1 (Intermediate 42A-1, 250 mg) and peak 2 (Intermediate 42B-1, 150 mg). Intermediate 42A-1: 99.85% chiral purity; MS (ESI) 727.58 [M+H] ⁺ . Intermediate 42B-1: 99.77% chiral purity; MS (ESI) 727.58 [M+H] ⁺ . The absolute stereochemistry of Intermediate 42A-1 and Intermediate 42B-1 was arbitrarily assigned.

Example 3A-1 (R,Z)-1 ⁶ -chloro-8 ⁶ -fluoro-1 ¹ ,2 ² ,5 ¹ ,3- tetramethyl -2 ⁴ ,2 ⁵ ,2 ⁶ ,2 ⁷ -tetrahydro-1 ¹ H,5 ¹ H-9-oxa-7-thia-3- aza-2(3,4)-pyrazolo[1,5-a]pyridina-1(7,3)-indola-5(3,5)-pyra zola-8(3,1)- naphthalenacyclododecaphane-1 ² - carboxylic acid [0206] To a stir -1 (250 mg, 0.344 mmol) in MeOH:THF:H2O (5.0:5.0:5.0 mL) at rt, LiOH•H2O (216 mg, 5.16 mmol) was added. The mixture stirred at 70 °C for 2 h. After completion of reaction, the solvent was evaporated. The mixture was acidified to pH 2 using 2.0N aqueous HCl. An off-white precipitate was collected by filtration. The product was washed with ice cold water and dried under vacuum to afford Example 3A-1 (151.0 mg, 61%, 99.61% chiral purity). ¹ H NMR (400 MHz, DMSO-d6) δ 13.35 (bs, 1H), 8.10- 7.98 (m, 2H), 7.53-7.19 (m, 4H), 6.68 , 1H), 5.00-4.04 (m, 7H), 3.79-3.51 (m, 8H), 3.05-3.02 (m, 2H), 2.66 (m, 1H), 2.49 (m, 2H), 2.33-2.08 (m, 4H), 1.89 (m, 6H). MS (ESI) 713.52 [M+H] ⁺ . Example 3B-1 (R,Z)-1 ⁶ -chloro-8 ⁶ -fluoro-1 ¹ ,2 ² ,5 ¹ ,3- tetramethyl -2 ⁴ ,2 ⁵ ,2 ⁶ ,2 ⁷ -tetrahydro-1 ¹ H,5 ¹ H-9-oxa-7-thia-3- aza-2(3,4)-pyrazolo[1,5-a]pyridina-1(7,3)-indola-5(3,5)-pyra zola-8(3,1)- naphthalenacyclododecaphane-1 ² - carboxylic acid [0207] To a stir B-1 (80 mg, 0.110 mmol) in MeOH:THF:H2O (1:1:1, 3 mL) at rt, LiOH•H2O (69 mg,1.65 mmol) was added, and the mixture was stirred at 70 °C for 2 h. After completion of reaction, the solvent was evaporated. The mixture was acidified to pH 2 using 2.0 N aqueous HCl. An off-white precipitate was collected by filtration. The product was washed with ice cold water and dried under vacuum to afford Example 3B-1 (19.7 mg, 26%, 99.87% chiral purity). ¹ H NMR (400 MHz, DMSO-d6) δ 13.3 (bs, 1H), 8.06- 8.01 (dd, J = 9.2, 6.0 Hz, 1H), 7.86 (d, J = H), 7.46-7.43 (dd, J = 10.4, 2.4 Hz, 1H), 7.28- 7.22 (m, 2H), 7.17 (d, J = 8.4, 1H), 6.88 (s, 1H), 4.75 (s, 1H), 4.48-4.37 (m, 3H), 4.08-3.78 (m, 2H), 3.95-3.73 (m, 5H), 3.51 (m, 1H), 3.33 (m, 3H), 3.00-2.89 (m, 3H), 2.32-2.20 (m, 2H), 2.08 (m, 1H), 1.95 (m, 3H), 1.83-1.63 (m, 3H), 1.57 (s, 3H). MS (ESI) 713.52 [M+H] ⁺ . [0208] As provided herein, both atropisomers, Example 3A-1 and Example 3B-1, were obtained. The absolute stereochemistry of Example 3A-1 and Example 3B-1 was arbitrarily assigned. Intermediate 43-1 Methyl (R)-7-(4-(((5-(((tert-butyldiphenylsilyl)oxy)methyl)-1-methy l-1H-pyrazol-3- yl)methyl)(methyl)amino)-2-methyl-5,6-dihydro-4H-pyrrolo[1,2 -b]pyrazol-3-yl)-6-chloro-3-(3- methoxy-3-oxopropyl)-1-methyl-1H-indole-2-carboxylate [0209] Intermediate ntermediate 27-1 by following the procedure for the preparation of Intermediate 36-1. MS (ESI) 821.41 [M+H] ⁺ . The absolute stereochemistry of Intermediate 43-1 was arbitrarily assigned.

Intermediate 44-1 Methyl (R)-6-chloro-7-(4-(((5-(hydroxymethyl)-1-methyl-1H-pyrazol-3 - yl)methyl)(methyl)amino)-2-methyl-5,6-dihydro-4H-pyrrolo[1,2 -b]pyrazol-3-yl)-3-(3-methoxy- 3-oxopropyl)-1-methyl-1H-indole-2-carboxylate [0210] Intermediate Intermediate 43-1 by following the procedure for the preparation of Intermediate 10-1. MS (LCMS) 583.97 [M+H] ⁺ . The absolute stereochemistry of Intermediate 44-1 was arbitrarily assigned. Intermediate 45-1 Methyl (R)-6-chloro-7-(4-(((5-(chloromethyl)-1-methyl-1H-pyrazol-3- yl)methyl)(methyl)amino)-2-methyl-5,6-dihydro-4H-pyrrolo[1,2 -b]pyrazol-3-yl)-3-(3-methoxy- 3-oxopropyl)-1-methyl-1H-indole-2-carboxylate [0211] Intermediate Intermediate 44-1 by following the procedure for the preparation of Intermediate 11-1. MS (LCMS) 601.61 [M+H] ⁺ . The absolute stereochemistry of Intermediate 45-1 was arbitrarily assigned.

Intermediate 46-1 Methyl (R)-7-(4-(((5-((acetylthio)methyl)-1-methyl-1H-pyrazol-3-yl) methyl)(methyl)amino)-2- methyl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)-6-chloro-3 -(3-methoxy-3-oxopropyl)-1- methyl-1H-indole-2-carboxylate [0212] Intermediate Intermediate 45-1 by following the procedure for the preparation of Intermediate 12-1. MS (LCMS) 642.84. The absolute stereochemistry of Intermediate 46-1 was arbitrarily assigned. Intermediate 47-1 Methyl (R)-6-chloro-7-(4-(((5-(((7-fluoro-4-hydroxynaphthalen-2-yl) thio)methyl)-1-methyl-1H- pyrazol-3-yl)methyl)(methyl)amino)-2-methyl-5,6-dihydro-4H-p yrrolo[1,2-b]pyrazol-3-yl)-3-(3- methoxy-3-oxopropyl)-1-methyl-1H-indole-2-carboxylate [0213] Intermediate ntermediate 46-1 by following the procedure for the preparation of Intermediate 13-1. MS (LCMS) 759.73 [M+H] ⁺ . The absolute stereochemistry of Intermediate 47-1 was arbitrarily assigned. Intermediate 48-1 methyl (R)-6-chloro-7-(4-(((5-(((7-fluoro-4-hydroxynaphthalen-2-yl) thio)methyl)-1-methyl-1H- pyrazol-3-yl)methyl)(methyl)amino)-2-methyl-5,6-dihydro-4H-p yrrolo[1,2-b]pyrazol-3-yl)-3-(3- hydroxypropyl)-1-methyl-1H-indole-2-carboxylate [0214] Intermediate 48-1 was synthesized from Intermediate 47-1 by following the procedure for the preparation of Intermediate 14-1. MS (LCMS) 731.57 [M+H] ⁺ . The absolute stereochemistry of Intermediate 48-1 was arbitrarily assigned. Intermediate 49A-1 Methyl (R,Z)-1 ⁶ -chloro-8 ⁶ -fluoro-1 ¹ ,2 ² ,5 ¹ ,3-tetramethyl-2 ⁵ ,2 ⁶ -dihydro-1 ¹ H,2 ⁴ H,5 ¹ H-9-oxa-7-thia- 3-aza-1(7,3)-indola-2(3,4)-pyrrolo[1,2-b]pyrazola-5(3,5)-pyr azola-8(3,1)- naphthalenacyclododecaphane-1 ² -carboxylate Intermediate 49B-1 Methyl (R,Z)-1 ⁶ -chloro-8 ⁶ -fluoro-1 ¹ ,2 ² ,5 ¹ ,3-tetramethyl-2 ⁵ ,2 ⁶ -dihydro-1 ¹ H,2 ⁴ H,5 ¹ H-9-oxa-7-thia- 3-aza-1(7,3)-indola-2(3,4)-pyrrolo[1,2-b]pyrazola-5(3,5)-pyr azola-8(3,1)- naphthalenacyclododecaphane-1 ² -carboxylate [0215] To a stirre 00 mg, 0.41 mmol) in DCM (11 mL) at 0 °C, di-tert-butyl diazo-1,2-dicarboxylate (283 mg, 1.23 mmol ) and TPP (323 mg, 1.23 mmol) were added, and the mixture was stirred at rt for 2 h. Progress of the reaction was monitored by TLC and LCMS. After completion, the mixture was diluted with DCM (20 mL) and washed with water (20 mL). The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated. The crude material was purified by flash chromatography (SiO2, 0-100% EtOAc:PE) to afford racemic methyl (R,Z)-1 ⁶ -chloro-8 ⁶ -fluoro-1 ¹ ,2 ² ,5 ¹ ,3-tetramethyl-2 ⁵ ,2 ⁶ - dihydro-1 ¹ H,2 ⁴ H,5 ¹ H-9-oxa-7-thia-3-aza-1(7,3)-indola-2(3,4)-pyrrolo[1,2- b]pyrazola-5(3,5)- pyrazola-8(3,1)-naphthalenacyclododecaphane-1 ² -carboxylate (78 mg, 26.77%). MS (LCMS) 713.78 [M+H] ⁺ . [0216] The reaction was performed in 2 more batches to afford 235 mg of racemic compound. The atropisomers were separated by chiral SFC chromatography (Chiralpak-IG (30 x 250) mm, 5µ, 50% acetonitrile : MeOH, 1:1) to give peak 1 (Intermediate 49A-1, 76 mg) and peak 2 (Intermediate 49B-1, 46 mg). Intermediate 49A-1: 99.89% chiral purity; MS (ESI) 713.81 [M+H] ⁺ . Intermediate 49B-1: 99.74% chiral purity; MS (ESI) 713.78 [M+H] ⁺ . The absolute stereochemistry of Intermediate 49A-1 and Intermediate 49B-1 was arbitrarily assigned. Example 4A-1 (R,Z)-1 ⁶ -chloro-8 ⁶ -fluoro-1 ¹ ,2 ² ,5 ¹ ,3-tetramethyl-2 ⁵ ,2 ⁶ -dihydro-1 ¹ H,2 ⁴ H,5 ¹ H-9-oxa-7-thia-3-aza- 1(7,3)-indola-2(3,4)-pyrrolo[1,2-b]pyrazola-5(3,5)-pyrazola- 8(3,1)- naphthalenacyclododecaphane-1 ² -carboxylic acid [0217] To a stir A-1 (76 mg, 0.106 mmol) in MeOH:THF:water (1:1:1, 3 mL) at rt, LiOH•H2O (38 mg, 1.59 mmol) was added, and the mixture was stirred at 70 °C for 2 h. Progress of the reaction was monitored by TLC and LCMS. After completion, the mixture was concentrated under reduced pressure. The resulting crude was acidified to pH 2 using 2N aqueous HCl. The product was collected by filtration and washed with water (10 mL). The product was dried under vacuum to afford Example 4A-1 (50 mg, 71.5 mmol, 66%, 99.9% chiral purity). ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 13.4 (brs, 1H), 10.8 (bs, 1H), 8.14- 8.12 (t, J = 6.4 Hz, 1H), 7 (d, J = 8.4 Hz, 1H), 7.50 (d, J = 6 Hz, 1H), 7.34-7.30 (m, 2H), 7.19 (d, J = 8.0 Hz, 1H), 6.64 (br, 1H), 4.98-4.51 (br, 2H), 4.4-3.98 (br, 5H), 3.77 (s, 5H), 3.69 (br, 2H), 3.48 (d, 2H), 3.08 (t, 3H), 2.51-2.20 (br, 4H), 1.96 (s, 4H). MS (ESI) 699.35 [M+H] ⁺ . Example 4B ^-1 (R,Z)-1 ⁶ -chloro-8 ⁶ -fluoro-1 ¹ ,2 ² ,5 ¹ ,3-tetramethyl-2 ⁵ ,2 ⁶ -dihydro-1 ¹ H,2 ⁴ H,5 ¹ H-9-oxa-7-thia-3-aza- 1(7,3)-indola-2(3,4)-pyrrolo[1,2-b]pyrazola-5(3,5)-pyrazola- 8(3,1)- naphthalenacyclododecaphane-1 ² -carboxylic acid [0218] To a stirred solution of Intermediate 49A-1 (46 mg, 0.064 mmol) in MeOH:THF:water (1:1:1, 3 mL) at rt. LiOH•H2O (23 mg, 0.967 mmol) was added, and the mixture was stirred at 70 °C for 2 h. Progress of the reaction was monitored by TLC and LCMS. After completion, the mixture was concentrated under reduced pressure, and the crude was acidified to pH 2 using 2N aqueous HCl. The product was collected by filtration and washed with water (10 mL). The product was collected and dried under vacuum to afford Example 4B-1 (12 mg, 17.5 mmol, 26.7% , 99.7% chiral purity). ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 13.4 (brs, 1H), 10.5 (bs, 1H), 8.30 (br, 1H), 7.63-7.61 (br, 3H 7.44 (t, 1H), 6.98 (d, J = 8.4 Hz, 1H), 6.25 (bs, 1H), 5.55 (br, 1H), 5.15 (br, 1H), 4.42-4.29 (br, 2H), 4.22-4.12 (br, 2H), 3.90 (br, 1H), 3.73 (s, 3H), 3.58- 3.46 (br, 5H), 3.22-2.92 (br, 3H), 2.80-2.66 (br, 2H), 2.36 (brs, 3H), 2.22 (brs, 4H). MS (ESI) 699.35 [M+H] ⁺ . [0219] As provided herein, both atropisomers, Example 4A-1 and Example 4B-1, were obtained. The absolute stereochemistry of Example 4A-1 and Example 4B-1 was arbitrarily assigned. Example A Mcl-1 Homogeneous Time Resolved Fluorescence (HTRF) Assay [0220] Binding to Bcl-2 proteins Mcl-1 was assessed using an HTRF assay. Background: FAM-Bak/Bad binds to surface pocket of the Bcl-2 protein family. This binding can be monitored by HTRF signals between anti-GST-Tb and FAM-peptide using GST-tagged Bcl proteins. Assay conditions: 4 nM Mcl-1, 100 nM FAM-Bak peptide, in 20 mM K Phosphate, pH 7.5, 50 mM NaCl, 1 mM EDTA, 0.005% Triton X-100 and 1% DMSO (final). Assay procedure: Compounds were tested in 10-dose IC50 mode, in singlicate, with 3-fold serial dilution starting at 10µM or 1 µM. Compound stock solutions were added to protein solution using Acoustic technology. The compounds were then incubated with protein for 10 min at rt. The respective FAM labeled peptide was added and incubated for another 10 min. Anti-GST-Tb was added. After 60 min at rt, the HTRF fluorescence signal ratio was measured. Curve fits were performed in GraphPad Prism 4 with “sigmoidal dose-response (variable slope)”; 4 parameters with Hill Slope. The results are shown in Table 1. Example B NCI-H929 Cell Proliferation Assay [0221] Cell proliferation was measured using the CellTiter-Glo® Luminescent Cell Viability Assay. The assay involved the addition of a single reagent (CellTiter-Glo® Reagent) directly to cells cultured in serum-supplemented medium. NCI-H929 (ATCC CRL-9068) cells were cultured according to ATCC recommendations and were seeded at 3,000 cells per well. [0222] Each compound evaluated was prepared as a DMSO stock solution (10 mM). Compounds were tested in duplicate on each plate, with a 10-point serial dilution curve (1:3 dilution). Compound treatment (1.0 μL) was added from the compound dilution plate to the cell plate. The highest compound concentration was 10 μM (final), with a 0.1% final DMSO concentration. Plates were then incubated at 37 °C, 5% CO ₂ . After 72 h of compound treatment, cell plates were equilibrated at rt for approximately 30 mins. An equi-volume amount of CellTiter- Glo® Reagent (40 μL) was added to each well. Plates were mixed for 2 mins on an orbital shaker to induce cell lysis and then incubated at rt for 10 mins to stabilize the luminescent signal. Luminescence was recorded using an Envision plate reader according to CellTiter-Glo protocol. IC50 of each compound was calculated using GraphPad Prism by nonlinear regression analysis. IC50 values are provided in Table 1.

Table 1 Examples Mcl-1 IC50 (nM) H929 IC50 (nM) gle . For H929 CTG IC50: A = a single IC50 ≤ 20 nM; B = a single IC50 >20 nM and < 100 nM; C = a single IC ₅₀ ≥100 nM. [0223] Furthermore, although the foregoing has been described in some detail by way of illustrations and examples for purposes of clarity and understanding, it will be understood by those of skill in the art that numerous and various modifications can be made without departing from the spirit of the present disclosure. Therefore, it should be clearly understood that the forms disclosed herein are illustrative only and are not intended to limit the scope of the present disclosure, but rather to also cover all modification and alternatives coming with the true scope and spirit of the disclosure provided herein.