Process for making polysubstituted indole oligomers

Abstract

Described herein are compounds comprising substituted indoles, methods of making substituted indoles, and methods of making oligomers comprising substituted indoles.

Description

WSGR Docket No. 63230-734.601PROCESS FOR MAKING POLYSUBSTITUTED INDOLE OLIGOMERS CROSS REFERENCE TO OTHER APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 738,110, filed December 23, 2024, which is hereby incorporated by reference in its entirety herein.FIELD OF THE DISCLOSURE

[0002] Described herein are compounds comprising substituted indoles, methods of making the substituted indoles, and oligomers comprising the substituted indoles.BACKGROUND

[0003] Melanins are ubiquitous biopolymers and are produced from phenols and catechols by a series of oxidations. They provide photoprotection, pigmentation, and redox activity to most life forms, as well as inspire synthetic materials with desirable optical, electronic, and mechanical properties. Eumelanin is a prominent member of the melanin family of naturally occurring pigments that are produced by nearly every organism. Eumelanin colors the skin, hair, and eyes of mammals. Despite years of effort, its molecular structure remains unknown, limiting our understanding of its biological function and our ability to design synthetic mimics.

[0004] Disclosed herein are compounds comprising substituted indoles, methods of making the substituted indoles, and oligomers comprising the substituted indoles. Several of the methods highlight an iterative chain growth (ICG) approach toward the preparation of oligomers comprising the substituted indoles. The ICG approach provides well-defined and repetitive units, affording novel compounds that are able to mimic the properties of melanins, and more specifically, of eumelanin.SUMMARY

[0005] In one aspect, the present disclosure provides a compound represented by the structure of Formula (I):or a pharmaceutically acceptable salt thereof, wherein:is selected from:WSGR Docket No. 63230-734.601OR6each R1is independently selected from hydrogen, Ci-6 alkyl, -C(O)R23, and -C(O)OR23; each R2is independently selected from hydrogen, halogen, Ci-6 alkyl, -Si(R20)3, and - B(R21)2;each R3is independently selected from hydrogen and Ci-6 alkyl;each R4is independently selected from hydrogen and Ci-6 alkyl;each R5and R6are independently selected from hydrogen, -Si(R20)3, and Ci-6 alkyl; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl; R7is selected from hydrogen, halogen, Ci-6 alkyl, and -B(R21)2;each R20is independently selected from Ci-6 alkyl;each R21is independently selected from -OR22;each R22is independently selected from hydrogen and Ci-6 alkyl; ortwo R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl;each R23is independently selected from Ci-6 alkyl which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, - NH2, -N(Ci-6alkyl)2, Ci-6 alkyl, -C1-6haloalkyl, and -O-Ci-6 alkyl; and m is selected from 1 to 20.

[0006] In an aspect, the present disclosure provides a compound represented by the structure of Formula (I- A):WSGR Docket No. 63230-734.601Formula (I- A);or a pharmaceutically acceptable salt thereof.

[0007] In an aspect, the present disclosure provides a compound represented by the structure of Formula (I-B):Formula (I-B);or a pharmaceutically acceptable salt thereof.

[0008] In an aspect, the present disclosure provides a compound represented by the structure of Formula (I-B):Formula (I-C);or a pharmaceutically acceptable salt thereof, wherein:m is selected from 1 to 20.

[0009] In an aspect, the present disclosure provides a process for the preparation of a compound represented by the structure of Formula (II):WSGR Docket No. 63230-734.601comprising a suitable cross-coupling reaction of:(i) contacting a compound represented by the structure of Formula (II-A) or Formula (II-A*):Formula (II-A*);wherein,each G1is independently a suitable boryl moiety;(ii) with a compound represented by the structure of Formula (II-B):Formula (II-B);wherein,X is a suitable halide;in the presence of a suitable solvent to afford a compound represented by the structure of Formula (II), or a pharmaceutically acceptable salt thereof, wherein:WSGR Docket No. 63230-734.601each R1is independently selected from hydrogen, Ci-6 alkyl, -C(O)R23, and - C(O)OR23;each R2is independently selected from hydrogen, halogen, Ci-6 alkyl, -Si(R20)3, and -B(R21)2;each R3is independently selected from hydrogen and Ci-6 alkyl;each R4is independently selected from hydrogen and Ci-6 alkyl;each R5and R6are independently selected from hydrogen, -Si(R20)3, and Ci-6 alkyl; orone R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl;each R7is independently selected from hydrogen, halogen, Ci-6 alkyl, and - B(R21)2;each R20is independently selected from Ci-6 alkyl;each R21is independently selected from -OR22;each R22is independently selected from hydrogen and Ci-6 alkyl; or two R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl; each R23is independently selected from Ci-6 alkyl which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, -N(Ci-6alkyl)2, Ci-6 alkyl, -C1-6haloalkyl, and -O-Ci-6 alkyl; andeach m is independently selected from 0 to 20.

[0010] In an aspect, the present disclosure provides a process for the preparation of a compound represented by the structure of Formula (III) or Formula (III*):WSGR Docket No. 63230-734.601comprising a suitable desilylation reaction of:(i) contacting a compound represented by the structure of Formula (III-A) or Formula (III-A*):Formula (III-A*); wherein,each G2is independently a suitable silyl moiety;(ii) with a suitable desilylation reagent,in the presence of a suitable solvent to afford a compound represented by the structure of Formula (III) or Formula (III*), or a pharmaceutically acceptable salt of any one thereof, wherein:each R1is independently selected from hydrogen, Ci-6 alkyl, -C(O)R23, and - C(O)OR23;each R2is independently selected from hydrogen, halogen, Ci-6 alkyl, -Si(R20)3, and -B(R21)2;each R3is independently selected from hydrogen and Ci-6 alkyl;each R4is independently selected from hydrogen and Ci-6 alkyl;each R5and R6are independently selected from hydrogen, -Si(R20)3, and Ci-6WSGR Docket No. 63230-734.601alkyl; orone R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl;each R7is independently selected from hydrogen, halogen, Ci-6 alkyl, and - B(R21)2;each R20is independently selected from Ci-6 alkyl;each R21is independently selected from -OR22;each R22is independently selected from hydrogen and Ci-6 alkyl; or two R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl;each R23is independently selected from Ci-6 alkyl which is optionally substituted with one or more substituents independently selected from halogen, -OH, - CN, -NO2, -NH2, -N(Ci-6alkyl)2, Ci-6alkyl, -Ci-6haloalkyl, and -O-Ci-6alkyl; and each m is independently selected from 0 to 20.

[0011] In an aspect, the present disclosure provides a process for the preparation of a compound represented by the structure of Formula (IV) or Formula (IV*):comprising a suitable borylation reaction of:(i) contacting a compound represented by the structure of Formula (IV-A) or Formula (IV- A*):WSGR Docket No. 63230-734.601R6O R7OR6OR5R6O R7R5O R1Formula (IV-A) or Formula (IV-A*); (ii) with a suitable borylation reagent,in the presence of a suitable solvent to afford a compound represented by the structure of Formula (IV) or Formula (IV*), or a pharmaceutically acceptable salt of any one thereof, wherein:each R1is independently selected from hydrogen, Ci-6 alkyl, -C(O)R23, and -C(O)OR23; each R2is independently selected from hydrogen, halogen, Ci-6 alkyl, -Si(R20)3, and - B(R21)2;each R3is independently selected from hydrogen and Ci-6 alkyl;each R4is independently selected from hydrogen and Ci-6 alkyl;each R5and R6are independently selected from hydrogen, -Si(R20)3, and Ci-6 alkyl; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl; each R7is independently selected from hydrogen, halogen, Ci-6 alkyl, and -B(R21)2; each R20is independently selected from Ci-6 alkyl;each R21is independently selected from -OR22;each R22is independently selected from hydrogen and Ci-6 alkyl; ortwo R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl;each R23is independently selected from Ci-6 alkyl which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, - NH2, -N(Ci-6alkyl)2, Ci-6 alkyl, -C1-6haloalkyl, and -O-Ci-6 alkyl; andeach m is independently selected from 0 to 20.WSGR Docket No. 63230-734.601INCORPORATION BY REFERENCE

[0012] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. To the extent publications and patents or patent applications incorporated by reference contradict the disclosure contained in the specification, the specification is intended to supersede and / or take precedence over any such contradictory material.BRIEF DESCRIPTION OF THE DRAWINGS

[0013] The novel features of the disclosure are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present disclosure will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the disclosure are utilized, and the accompanying drawings (also “figure” and “FIG.” herein), of which:

[0014] FIG. 1 Absorption and emission spectra of monomer S9 and monomer la in acetonitrile and cyclohexane. Absorption and emission spectra of DHI in aqueous solution.Absorption and emission spectra are shown by dashed and solid curves, respectively;

[0015] FIG. 2 Absorption and emission spectra in acetonitrile and cyclohexane of dimer 9, trimer 10, tetramer 11, and pentamer 12. Absorption and emission spectra are shown by dashed and solid curves, respectively;

[0016] FIG. 3 (Top panel) Wavelength of the 0-0 vibronic emission peak maximum as an estimate of the electronic origin (gray circles) vs. the number of acetonide-protected monomers, n. The solid curve is a fit to the model from ref. 70. Absorption peak maxima vs. the number of repeating units for oligo(l,4-phenylene) in THF (middle panel) and oligo(aryleneethenylene) in THF (bottom panel). Data in the middle and bottom panels are from H. Meier, U. Stalmach, H. Kolshorn, Acta Polym. 1997, 48, 379-384. For each graph, the asymptotic estimate of the absorption onset for the infinitely long polymer (λ∞) is shown;

[0017] FIG. 4 Absorption spectra of monomer S9, dimer 9, and trimer 10 measured in cyclohexane (C6H12) or acetonitrile (CH3CN), as indicated. Spectra were recorded from freshly prepared solutions (black curves) and from the same solutions 20 months later (gray curves);

[0018] FIG. 5 Absorption spectra of monomer S9, dimer 9, trimer 10, tetramer 11, and pentamer 12 in acetonitrile before (black curves) and after (gray curves) irradiation for 30 minutes by 100 fs laser pulses (1 kHz pulse repetition rate; incident energy density 170 μJ cm-2; center wavelength of 300 nm for the monomer and dimer, 315 nm for the trimer, tetramer, andWSGR Docket No. 63230-734.601pentamer); and

[0019] FIG. 6 (Top panel) Extinction spectrum of dimer 9 (gray curve) compared with the sum of the extinction spectrum of monomer la plus the extinction spectrum of monomer S9 (black curve). (Middle panel) Extinction spectrum of trimer 10 (dark gray curve) compared with the sum of twice the extinction spectrum of monomer la plus the extinction spectrum of monomer S9 (light gray curve). (Bottom panel) Extinction spectra of monomers S9 (gray curve) and la (light gray curve). All spectra were recorded in cyclohexane solution and extinction values are believed to be accurate to within 10%.; and

[0020] FIG. 7 Normalized emission spectra of dimer 9, trimer 10, tetramer 11 and pentamer 12 in cyclohexane. The latter three curves were shifted along the frequency axis to align the long wavelength emission band with that of the dimer.DETAILED DESCRIPTION OF THE DISCLOSURE

[0021] Melanins are ubiquitous biopolymers and are produced from phenols and catechols by a series of oxidations. They provide photoprotection, pigmentation, and redox activity to most life forms, as well as inspire synthetic materials with desirable optical, electronic, and mechanical properties. Eumelanin is a prominent member of the melanin family of naturally occurring pigments that are produced by nearly every organism. Eumelanin colors the skin, hair, and eyes of mammals. Despite years of effort, its molecular structure remains unknown, limiting our understanding of its biological function and our ability to design synthetic mimics. Like other members of the Melanin family, Eumelanin is produced by aerobic oxidation of phenols and catechols derivatives. These aerobic, oxidative synthetic routes afford a complex mixture of poorly soluble molecules that prevent identification of any well-defined or repetitive units. As such, the variables that influence Eumelanin’ s remarkable properties remain obscure, preventing the creation of novel synthetic materials that are able to mimic the properties of Melanins, and more specifically, of Eumelanin.

[0022] Disclosed herein are compounds comprising substituted indoles, methods of making substituted indoles, and methods of making oligomers comprising substituted indoles. Several methods highlight an iterative chain growth (ICG) approach for the preparation of oligomers comprising the substituted indoles. This ICG approach provides well-defined and repetitive indole units.

[0023] Two earlier efforts at identifying the structure have been reported in the literature, only one of which disclosed a synthetic route, which is neither convenient nor scalable. In the 1970s, Ito and Nicol isolated a methylated tetramer of 5, 6-dihydroxyindole-2-carboxylic acid (DHICA)WSGR Docket No. 63230-734.601from the tapetum lucidum of catfish (Ito S., & Nicol. J. A. C., Isolation of oligomers of 5,6-dihydroxyindole-2-carboxylic acid from the eye of the catfish. Biochemical Journal 143, 207-217 (1974)). Starting in the 1980s, Prota and d’Ischia, with various co-workers over the years, began investigating the products of biomimetic oxidations of 5, 6-dihydroxyindole (DHI) and DHICA, isolating a number of oligomers over the years with covalent bonds at primarily the C2, C4, and C7 positions up to 5-units in length (z.e., see, Pezzella A., Napolitano A., d’Ischia M., & Prota G., Oxidative polymerisation of 5,6-dihydroxyindole-2-carboxylic acid to melanin: A new insight.Tetrahedron, 52, 7913-7920 (1996) and Arzillo M., Pezzella A., Crescenzi O., Napolitano A., Land E. J., Barone V., & d’Ischia M., Cyclic Structural Motifs in 5,6-Dihydroxyindole Polymerization Uncovered: Biomimetic Modular Buildup of a Unique Five-Membered Macrocycle. Org. Lett., 12, 3250-3253 (2010)). However, those routes are hampered by poor selectivity, low yields, and challenging purifications.Scheme A. Proposed biosynthesis of eumelanin and isolated tetramer by Ito and Nicoltetramer

[0024] The proposed biosynthesis of eumelanin starts from L-tyrosine. After a series of aerobic oxidations of L-tyrosine, a mixture of 5, 6-dihydroxyindole (DHI) and 5, 6-dihydroxyindole-2-carboxylic acid (DHICA) can be obtained, although these species readily undergo further aerobic oxidation to yield eumelanin granules: heterogeneous particles approximately 100s of nm in diameter comprising mixed oxidation states of DHI and DHICA. In 1970s, after extraction of tapetum lucidum from catfish and methylation, Ito and Nicol isolated a tetramer of DHICA (Scheme A).Scheme B. Prota, d’Ischia and co-workers biomimetic oxidations results of DHIWSGR Docket No. 63230-734.601OAc AcO OAc6% yield < 1% from DHI yield fromDHI and 2,4 '-2 2 "-trimer

[0025] These route by Prota, dTschia, and co-workers are hampered by poor selectivity, low yields, and challenging purifications. As such, these routes are not suitable for rational synthesis of eumelanin or eumelanin analogs nor are they viable for scale-up.

[0026] Disclosed herein is an iterative chain growth (ICG) approach for the preparation of oligomers comprising substituted indoles.Improved Preparation of substituted indoles and oligomers comprising substituted indoles

[0027] The preparation of substituted indoles and oligomers comprising substituted indoles is shown in Scheme 1.

[0028] Scheme 1. Iterative Chain Growth (ICG) ApproachSuitable Pd catalyst Suitable base Suitable solventq1is a suitable boryl moiety; is a suitable halide; andm is 0.Suitable Pd catalyst Suitable base Suitable solventis a suitable boryl moiety; is a suitable halide; and each m is independently selected from 0 to 20.WSGR Docket No. 63230-734.601(2-A)2is a suitable silyl moiety.(3-A)

[0029] In some embodiments, the preparation commences with any one of the steps selected from a suitable cross-coupling reaction as illustrated by step (1-A) or step (1-B); a suitable desilylation reaction as illustrated by step (2-A) or step (2-B); and a suitable borylation reaction as illustrated by step (3-A) or step (3-B). In some cases, the preparation commences with the steps selected from step (1-A), step (1-B), step (2-A), step (2-B), step (3-A), and step (3-B). In some cases, the preparation commences with the steps selected from step (1-A), step (2-A), and step (3-A). In some cases, the preparation commences with the steps selected from step (1-B), step (2-B), and step (3-B). In some cases, the preparation terminates with the steps selected from step (1-A),WSGR Docket No. 63230-734.601step (1-B), step (2-A), step (2-B), step (3-A), and step (3-B). In some cases, the preparation terminates with the steps selected from step (1-A), step (2-A), and step (3-A). In some cases, the preparation terminates with the steps selected from step (1-B), step (2-B), and step (3-B).

[0030] In some embodiments, for the preparation of substituted indoles and oligomers comprising substituted indoles, Step (1-A) or step (1-B) is the chain extension step of the ICG approach disclosed herein. In some cases, step (2-A) or step (2-B) is the unmasking step of the ICG approach disclosed herein. In some cases, step (3-A) or step (3-B) is the functional step of the ICG approach disclosed herein. In some cases, when the steps selected from step (1-A), step (1-B), step (2-A), step (2-B), step (3-A), and step (3-B) are arranged in a suitable synthetic sequence the preparation of substituted indoles and oligomers comprising substituted indoles of the present disclosure are obtained. In some cases, when the step is selected from step (1-A), step (2-A), step (2-B), and step (3-A), the preparation of substituted indoles of the present disclosure are obtained. In some cases, when the step is selected from step (1-B), step (2-B), and step (3-B), the preparation of oligomers comprising substituted indoles of the present disclosure are obtained. Compounds

[0031] In an aspect, the present disclosure provides a compound represented by the structure of Formula (I):or a pharmaceutically acceptable salt thereof, wherein:( )is selected from:hydrogen, halogen, Ci-6 alkyl, -Si(R20)3, -B(R21)2,WSGR Docket No. 63230-734.601OR5R5O— ( / \each R1is independently selected from hydrogen, Ci-6 alkyl, -C(O)R23, and -C(O)OR23; each R2is independently selected from hydrogen, halogen, Ci-6 alkyl, -Si(R20)3, and - B(R21)2;each R3is independently selected from hydrogen and Ci-6 alkyl;each R4is independently selected from hydrogen and Ci-6 alkyl;each R5and R6are independently selected from hydrogen, -Si(R20)3, and Ci-6 alkyl; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl; R7is selected from hydrogen, halogen, Ci-6 alkyl, and -B(R21)2;each R20is independently selected from Ci-6 alkyl;each R21is independently selected from -OR22;each R22is independently selected from hydrogen and Ci-6 alkyl; ortwo R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl;each R23is independently selected from Ci-6 alkyl which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, - NH2, -N(Ci-6alkyl)2, Ci-6 alkyl, -C1-6haloalkyl, and -O-Ci-6 alkyl; and m is selected from 1 to 20.f A \

[0032] In some embodiments, for a compound or salt of Formula (I), is selectedOR5N4y^R2 R2>3 hydrogen, halogen, Ci-6 alkyl, -Si(R20)3, -B(R21)2,WSGR Docket No. 63230-734.601. In some cases,is selected hydrogen, halogen, -Si(R20)3, -B(R21)2, and In some cases, is selected hydrogen, halogen, -Si(R20)3, -B(R21)2, andselected from hydrogen, -Si(Me)3, -Si(Et)3, -B(OH)2, -B(OMe)2, -B(O1Pr)2, -Bpin, -Bneop,WSGR Docket No. 63230-734.601, wherein m is selected from 1 to 20. In some cases,is selectedWSGR Docket No. 63230-734.601from hydrogen, Si(Me)3, -Bpin, and is selectedfrom hydrogen, Si(Me)3, -Bpin,and wherein m is selected from 1 to 20.In some cases,is selected from hydrogen, Si(Me)3, -Bpin,andcases,is selected from hydrogen, -Si(R20)3, and -B(R21)2. In some cases,from hydrogen, -Si(Me)3, -Si(Et)3, -Si(1Pr)3, -Si(nButyl)3, -Si(OMe)3, -Si(0Et)3, -Si(O1Pr)3,Si(OnButyl)3, -B(OH)2, -B(OMe)2, -B(OiPr)2, -Bpin, -Bneop, and -Bcat. In some cases,selected from hydrogen, -Si(Me)3, -Si(Et)3, -B(OH)2, -B(OMe)2, -B(O1Pr)2, -Bpin, and -Bneop. Insome cases,is selected from hydrogen, -Si(Me)3, -Si(Et)3, -Bpin, and -Bneop. In somecases,is selected from hydrogen, -Si(Me)3, and -Bpin. In some cases,' is selected fromWSGR Docket No. 63230-734.601, wherein m is selected from 1 to 20. In some cases,is selectedfrom. In some cases, m is selected from 1 to 30. In some cases, m is selected from 1 to 25. In some cases, m is selected from 1 to 20. In some cases, m is selected from 1 to 15. In some cases, m is selected from 1 to 10. In some cases, m is selected from 1 to 5. In some cases, m is selected from 5 to 10. In some cases, m is selected from 5 to 15. In some cases, m is selected from 5 to 20. In some cases, m is selected from 2 to 30. In some cases, m is selected from 2 to 25. In some cases, m is selected from 2 to 20. In some cases, m is selected from 2 to 15. In some cases, m is selected from 2 to 10. In some cases, m is selected from 3 to 30. In some cases, m is selected from 3 to 25. In some cases, m is selected from 3 to 20. In some cases, m is selected from 3 to 15. In some cases, m is selected from 3 to 10. In some cases, m is 1. In some cases, m is 2. In some cases, m is 3. In some cases, m is 4. In some cases, m is 5. In some cases, m is 6. In someWSGR Docket No. 63230-734.601cases, m is 7. In some cases, m is 8. In some cases, m is 9. In some cases, m is 10. In some cases, m is 11. In some cases, m is 12. In some cases, m is 13. In some cases, m is 14. In some cases, m is 15. In some cases, m is 16. In some cases, m is 17. In some cases, m is 18. In some cases, m is 19. In some cases, m is 20. In some cases, m is 21. In some cases, m is 22. In some cases, m is 23. In some cases, m is 24. In some cases, m is 25. In some cases, m is less than 35. In some cases, m is less than 30. In some cases, m is less than 25. In some cases, m is less than 20.

[0033] In some embodiments, for a compound or salt of Formula (I), each R1is independently selected from hydrogen, Ci-6 alkyl, -C(O)R23, and -C(O)OR23. In some cases, each R1is independently selected from hydrogen, -CH3, -CH2CH3, -CH(CH3)2, -CH2CH2CH3, -C(CH3)3, -CH2CH2CH2CH3, -C(O)R23, and -C(O)OR23. In some cases, each R1is independently selected from hydrogen, -CH3, -CH2CH3, -CH(CH3)2, -C(O)R23, and -C(O)OR23. In some cases, each R1is independently selected from hydrogen, -CH3, -CH2CH3, -C(O)R23, and -C(O)OR23. In some cases, each R1is independently selected from hydrogen, -C(O)R23, and -C(O)OR23. In some cases, each R1is independently selected from hydrogen, -C(O)CH3, -C(O)C(CH3)3, and -C(O)OR23. In some cases, each R1is independently selected from hydrogen and -C(O)OR23. In some cases, each R1is independently selected from hydrogen, -C(O)OCH3, -C(O)OCH(CH3)2, and -C(O)OC(CH3)3. In some cases, each R1is independently selected from hydrogen, -C(O)OCH3, and -C(O)OC(CH3)3. In some cases, each R1is independently selected from hydrogen and -C(O)OC(CH3)3. In some cases, each R1is independently selected from hydrogen. In some cases, R1is hydrogen. In some cases, R1is -C(O)OC(CH3)3.

[0034] In some embodiments, for a compound or salt of Formula (I), each R2is independently selected from hydrogen, halogen, Ci-6 alkyl, -Si(R20)3, and -B(R21)2. In some cases, each R2is independently selected from hydrogen, Ci-6 alkyl, -Si(R20)3, and -B(R21)2. In some cases, eachR2is independently selected from hydrogen, -CH3, -CH2CH3, -CH(CH3)2, -CH2CH2CH3, -C(CH3)3, -Si(R20)3, and -B(R21)2. In some cases, each R2is independently selected from hydrogen, -CH3, -CH2CH3, -Si(R20)3, and -B(R21)2. In some cases, each R2is independently selected from hydrogen, -Si(R20)3, and -B(R21)2. In some cases, each R2is independently selected from hydrogen, -Si(Me)3, -Si(Et)3, -Si(iPr)3, -Si(nButyl)3, -Si(OMe)3, -Si(OEt)3, -Si(OiPr)3, Si(OnButyl)3, -B(OH)2, -B(OMe)2, -B(O1Pr)2, -Bpin, -Bneop, and -Beat. In some cases, each R2is independently selected from hydrogen, -Si(Me)3, -Si(Et)3, -Si(nButyl)3, -B(OH)2, -B(OMe)2, -B(O1Pr)2, -Bpin, and -Bneop. In some cases, each R2is independently selected from hydrogen, -Si(Me)3, -Si(Et)3, -B(OMe)2, -B(O1Pr)2, -Bpin, and -Bneop. In some cases, each R2is independently selected from hydrogen, -Si(Me)3, -Si(Et)3, -Bpin, and -Bneop. In some cases, each R2is independently selected from hydrogen, -Si(Me)3, -Bpin, and -Bneop. In some cases, each R2is independently selectedWSGR Docket No. 63230-734.601from hydrogen, -Si(Me)3, and -Bpin. In some cases, each R2is independently selected from -Si(Me)3 and -Bpin. In some cases, each R2is independently selected from hydrogen and -Bpin. In some cases, each R2is independently selected from hydrogen and -Si(Me)3. In some cases, each R2is independently selected from -Bpin. In some cases, each R2is independently selected from hydrogen. In some cases, each R2is independently selected from -Si(Me)3.

[0035] In some embodiments, for a compound or salt of Formula (I), each R3is independently selected from hydrogen and Ci-6 alkyl. In some cases, each R3is independently selected from hydrogen and Ci-4 alkyl. In some cases, each R3is independently selected from hydrogen, -CH3, -CH2CH3, -CH(CH3)2, -CH2CH2CH3, and -C(CH3)3. In some cases, each R3is independently selected from hydrogen, -CH3, -CH2CH3, -CH(CH3)2, and -CH2CH2CH3. In some cases, each R3is independently selected from hydrogen, -CH3, -CH2CH3, and -CH2CH2CH3. In some cases, each R3is independently selected from hydrogen, -CH3, and -CH2CH3. In some cases, each R3is independently selected from hydrogen and -CH3. In some cases, each R3is independently selected from hydrogen.

[0036] In some embodiments, for a compound or salt of Formula (I), each R4is independently selected from hydrogen and Ci-6 alkyl. In some cases, each R4is independently selected from hydrogen and C1-4 alkyl. In some cases, each R4is independently selected from hydrogen, -CH3, -CH2CH3, -CH(CH3)2, -CH2CH2CH3, and -C(CH3)3. In some cases, each R4is independently selected from hydrogen, -CH3, -CH2CH3, -CH(CH3)2, and -CH2CH2CH3. In some cases, each R4is independently selected from hydrogen, -CH3, -CH2CH3, and -CH2CH2CH3. In some cases, each R4is independently selected from hydrogen, -CH3, and -CH2CH3. In some cases, each R4is independently selected from hydrogen and -CH3. In some cases, each R4is independently selected from hydrogen.

[0037] In some embodiments, for a compound or salt of Formula (I), R7is selected from hydrogen, halogen, Ci-6 alkyl, and -B(R21)2. In some cases, R7is selected from hydrogen, halogen, C1.4 alkyl, and -B(R21)2. In some cases, R7is selected from hydrogen, halogen, -CH3, -CH2CH3, -CH(CH3)2, -CH2CH2CH3, -C(CH3)3, and -B(R21)2. In some cases, R7is selected from hydrogen, halogen, -CH3, -CH2CH3, -CH(CH3)2, and -B(R21)2. In some cases, R7is selected from hydrogen, halogen, and -B(R21)2. In some cases, R7is selected from hydrogen, halogen, -B(OH)2, -B(OMe)2, -B(O1Pr)2, -Bpin, -Bneop, and -Beat. In some cases, R7is selected from hydrogen, halogen, -B(OH)2, -B(OMe)2, -B(O1Pr)2, -Bpin, and -Bneop. In some cases, R7is selected from hydrogen, halogen, -B(OH)2, -Bpin, and -Bneop. In some cases, R7is selected from hydrogen, halogen, -Bpin, and -Bneop. In some cases, R7is selected from hydrogen, halogen, and -Bpin. In some cases, R7is selected from hydrogen, bromo, iodo, and -B(R21)2. In some cases, R7is selected fromWSGR Docket No. 63230-734.601hydrogen, bromo, iodo, -B(OH)2, -B(OMe)2, -B(OiPr)2, -Bpin, -Bneop, and -Bcat. In some cases, R7is selected from hydrogen, bromo, iodo, -B(OH)2, -B(OMe)2, -B(OiPr)2, -Bpin, and -Bneop. In some cases, R7is selected from hydrogen, bromo, iodo, -B(OH)2, -Bpin, and -Bneop. In some cases, R7is selected from hydrogen, bromo, iodo, -Bpin, and -Bneop. In some cases, R7is selected from hydrogen, bromo, iodo, and -Bpin. In some cases, R7is selected from hydrogen, iodo, -B(R21)2. In some cases, R7is selected from hydrogen, iodo, -B(OH)2, -B(OMe)2, -B(OiPr)2, -Bpin, -Bneop, and -Bcat. In some cases, R7is selected from hydrogen, iodo, -B(OH)2, -B(OMe)2, -B(OiPr)2, -Bpin, and -Bneop. In some cases, R7is selected from hydrogen, iodo, -B(OH)2, -Bpin, and -Bneop. In some cases, R7is selected from hydrogen, bromo, -Bpin, and -Bneop. In some cases, R7is selected from hydrogen, bromo, and -Bpin. In some cases, R7is selected from hydrogen, iodo, -Bpin, and -Bneop. In some cases, R7is selected from hydrogen, iodo, and -Bpin.

[0038] In some embodiments, for a compound or salt of Formula (I), each R5and R6are independently selected from hydrogen, -Si(R20)3, and Ci-6 alkyl; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl. In some cases, each R5and R6are independently selected from -Si(R20)3 and Ci-6 alkyl; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl. In some cases, each R5and R6are independently selected from -Si(R20)3, and Ci-6 alkyl; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-4 alkyl. In some cases, each R5and R6are independently selected from -Si(R20)3, and Ci-6 alkyl; or one R5and one R6are taken together to form a 5- to 6-membered heterocycle which is optionally substituted with one or more substituents independently selected from Ci-4 alkyl. In some cases, each R5and R6are independently selected from -Si(Me)3, -Si(Et)3, -Si(1Pr)3, -Si(nButyl)3, and Ci-6 alkyl; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-4 alkyl. In some cases, each R5and R6are independently selected from -Si(Me)3, -Si(Et)3, -Si(iPr)3, -CH3, -CH2CH3, -CH(CH3)2, -CH2CH2CH3, and -C(CH3)3; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from CM alkyl. In some cases, each R5and R6are independently selected from -Si(Me)3, -Si(Et)3, -Si(1Pr)3, -CH3, and -C(CH3)3; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from CM alkyl. In some cases, each R5and R6are independently selected from -Si(Me)3, -Si(Et)3, -Si(1Pr)3, -CH3, and -C(CH3)3; or one R5and one R6are taken together to form a 5- to 6-membered heterocycle which is optionally substituted withWSGR Docket No. 63230-734.601one or more substituents independently selected from CM alkyl. In some cases, each R5and R6are independently selected from -Si(Et)3, -Si(iPr)3, and -CH3; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from C1-4 alkyl. In some cases, each R5and R6are independently selected from -Si(1Pr)3 and -CH3; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from CM alkyl.. In some cases, each R5and R6are independently selected from -Si(1Pr)3 and -CH3; or one R5and one R6are taken together to form a 5- to 6-membered heterocycle which is optionally substituted with one or more substituents independently selected from CM alkyl. In some cases, each R5and R6are independently selected from -Si(iPr)3 and -CH3; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from -CH3, -CH2CH3, -CH(CH3)2, -CH2CH2CH3, and -C(CH3)3 In some cases, each R5and R6are independently selected from -Si(iPr)3 and -CH3; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from -CH3. In some cases, each R5and R6are independently selected from -Si(1Pr)3 and -CH3; or one R5and one R6are taken together to form a 5- to 6-membered heterocycle which is optionally substituted with one or more substituents independently selected from -CH3. In some cases, each R5and R6are independently selected from hydrogen, -Si(R20)3, and Ci-6 alkyl; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from CM alkyl. In some cases, each R5and R6are independently selected from hydrogen, -Si(Me)3, -Si(Et)3, -Si(1Pr)3, -Si(nButyl)3, and Ci-6 alkyl; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from CM alkyl. In some cases, each R5and R6are independently selected from hydrogen, -Si(Me)3, -Si(Et)3, -Si(1Pr)3, -Si(nButyl)3, and Ci-6 alkyl; or one R5and one R6are taken together to form a 5- to 6-membered heterocycle which is optionally substituted with one or more substituents independently selected from CM alkyl. In some cases, each R5and R6are independently selected from hydrogen, -Si(Me)3, -Si(Et)3, -Si(1Pr)3, -CH3, -CH2CH3, -CH(CH3)2, -CH2CH2CH3, and -C(CH3)3; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from C1-4 alkyl. In some cases, each R5and R6are independently selected from hydrogen, -Si(Me)3, -Si(Et)3, -Si(1Pr)3, -CH3, and -C(CH3)3; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from C1.4 alkyl. In some cases, each R5and R6are independently selected from hydrogen, -Si(Et)3, -Si(1Pr)3, and -CH3; or one R5and one R6are taken together to form a heterocycle which isWSGR Docket No. 63230-734.601optionally substituted with one or more substituents independently selected from CM alkyl. In some cases, each R5and R6are independently selected from hydrogen, -Si(Et)3, -Si(iPr)3, and -CH3; or one R5and one R6are taken together to form a 5- to 6-membered heterocycle which is optionally substituted with one or more substituents independently selected from CM alkyl. In some cases, each R5and R6are independently selected from hydrogen, -Si(iPr)3, and -CH3; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from C1-4 alkyl. In some cases, each R5and R6are independently selected from hydrogen, -Si(iPr)3, and -CH3; or one R5and one R6are taken together to form a 5- to 6-membered heterocycle which is optionally substituted with one or more substituents independently selected from C1-4 alkyl. In some cases, each R5and R6are independently selected from hydrogen, -Si(iPr)3, and -CH3; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from -CH3, -CH2CH3, -CH(CH3)2, -CH2CH2CH3, -C(CH3)3. In some cases, each R5and R6are independently selected from hydrogen, -Si(iPr)3, and -CH3; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from -CH3. In some cases, each R5and R6are independently selected from hydrogen, -Si(iPr)3, and -CH3; or one R5and one R6are taken together to form a 5- to 6-membered heterocycle which is optionally substituted with one or more substituents independently selected from -CH3.

[0039] In some embodiments, for a compound or salt of Formula (I), each R20is independently selected from Ci-6 alkyl. In some cases, each R20is independently selected from Ci- 4 alkyl. In some cases, each R20is independently selected from -CH3, -CH2CH3, -CH(CH3)2, -CH2CH2CH3, and -C(CH3)3. In some cases, each R20is independently selected from -CH3, -CH2CH3, -CH(CH3)2, and -CH2CH2CH3. In some cases, each R20is independently selected from -CH3, -CH2CH3, and -CH(CH3)2. In some cases, each R20is independently selected from -CH(CH3)2. In some cases, each R20is independently selected from -CH2CH3 and -CH(CH3)2. In some cases, each R20is independently selected from -CH3 and -CH(CH3)2. In some cases, each R20is independently selected from -CH3 and -CH2CH3.

[0040] In some embodiments, for a compound or salt of Formula (I), each R21is independently selected from -OR22.

[0041] In some embodiments, for a compound or salt of Formula (I), each R22is independently selected from hydrogen and Ci-6 alkyl; or two R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl. In some cases,WSGR Docket No. 63230-734.601each R22is independently selected from hydrogen and Ci-6 alkyl; or two R22on different O atoms are taken together with the O atom to which each R22is attached to form a 5- to 6-membered heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl. In some cases, each R22is independently selected from hydrogen, -CH3, -CH2CH3, and -CH(CH3)2; or two R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl. In some cases, each R22is independently selected from hydrogen, -CH3, -CH2CH3, and -CH(CH3)2; or two R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle which is optionally substituted with one or more substituents independently selected from CM alkyl. In some cases, each R22is independently selected from hydrogen, -CH3, -CH2CH3, and -CH(CH3)2; or two R22on different O atoms are taken together with the O atom to which each R22is attached to form a 5- to 6-membered heterocycle which is optionally substituted with one or more substituents independently selected from CM alkyl. In some cases, each R22is independently selected from hydrogen, -CH3, and -CH(CH3)2; or two R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle which is optionally substituted with one or more substituents independently selected from CM alkyl. In some cases, each R22is independently selected from hydrogen; or two R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle which is optionally substituted with one or more substituents independently selected from C1-10alkyl. In some cases, each R22is independently selected from hydrogen; or two R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle which is optionally substituted with one or more substituents independently selected from CM alkyl. In some cases, each R22is independently selected from hydrogen; or two R22on different O atoms are taken together with the O atom to which each R22is attached to form a 5- to 6-membered heterocycle which is optionally substituted with one or more substituents independently selected from CM alkyl. In some cases, each R22is independently selected from hydrogen; or two R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle which is optionally substituted with one or more substituents independently selected from -CH3, -CH2CH3, and -CH(CH3)2. In some cases, two R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle, which is optionally substituted with one or more substituents independently selected from Ci-6 alkyl. In some cases, two R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle, which is optionally substituted with one or more substituents independently selected from CM alkyl. InWSGR Docket No. 63230-734.601some cases, two R22on different O atoms are taken together with the O atom to which each R22is attached to form a 5- to 6-membered heterocycle, which is optionally substituted with one or more substituents independently selected from CM alkyl. In some cases, two R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle, which is optionally substituted with one or more substituents independently selected from -CH3, -CH2CH3, and -CH(CH3)2. In some cases, two R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle, which is optionally substituted with one or more substituents independently selected from -CH3 and -CH2CH3. In some cases, two R22on different O atoms are taken together with the O atom to which each R22is attached to form a 5- to 6-membered heterocycle, which is optionally substituted with one or more substituents independently selected from -CH3 and -CH2CH3. In some cases, two R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle, which is optionally substituted with one or more substituents independently selected from -CH3. In some cases, two R22on different O atoms are taken together with the O atom to which each R22is attached to form a 5- to 6-membered heterocycle, which is optionally substituted with one or more substituents independently selected from -CH3.

[0042] In some embodiments, for a compound or salt of Formula (I), each R23is independently selected from Ci-6 alkyl which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, -N(CI-6 alkyl)2, Ci-6 alkyl, -C1-6haloalkyl, and -O-Ci-6 alkyl. In some cases, each R23is independently selected from Ci-6 alkyl which is optionally substituted with one or more substituents independently selected from fluoro, chloro, -OH, -CN, Ci-6 alkyl, -C1-6haloalkyl, and -O-Ci-6 alkyl. In some cases, each R23is independently selected from Ci-6 alkyl which is optionally substituted with one or more substituents independently selected from fluoro, Ci-6 alkyl, -Ci-6 haloalkyl, and -O-Ci-6 alkyl. In some cases, each R23is independently selected from Ci-6 alkyl which is optionally substituted with one or more substituents independently selected from Ci-6 alkyl, -Ci-6 haloalkyl, and -O-Ci-6 alkyl. In some cases, each R23is independently selected from Ci-6 alkyl which is optionally substituted with one or more substituents independently selected from fluoro, Ci-6 alkyl, and -O-Ci-6 alkyl. In some cases, each R23is independently selected from Ci-6 alkyl. In some cases, each R23is independently selected from -CH3, -CH2CH3, -CH(CH3)2, -CH2CH2CH3, and -C(CH3)3. In some cases, each R23is independently selected from -CH3, -CH(CH3)2, and -C(CH3)3. In some cases, each R23is independently selected from -CH3 and -C(CH3)3. In some cases, each R23is independently selected from -C(CH3)3. In some cases, each R23is independently selected from -CH3.WSGR Docket No. 63230-734.601

[0043] In some embodiments, Formula (I) is represented by the structure of Formula (I-A):Formula (I-A);or a pharmaceutically acceptable salt thereof.

[0044] In some embodiments, Formula (I) is represented by the structure of Formula (I-B):or a pharmaceutically acceptable salt thereof.

[0045] In some embodiments, Formula (I) is represented by the structure of Formula (I-C):R6O R7R5O R1OR6R4OR5R4R6OR3R1R2Formula (I-C);or a pharmaceutically acceptable salt thereof, wherein:m is selected from 1 to 20.

[0046] In some embodiments, for a compound or salt of Formula (I) or Formula (I-C), m is selected from 1 to 30. In some cases, m is selected from 1 to 25. In some cases, m is selected from 1 to 20. In some cases, m is selected from 1 to 15. In some cases, m is selected from 1 to 10. In some cases, m is selected from 1 to 5. In some cases, m is selected from 5 to 10. In some cases, m is selected from 5 to 15. In some cases, m is selected from 5 to 20. In some cases, m is selected from 2 to 30. In some cases, m is selected from 2 to 25. In some cases, m is selected from 2 to 20.WSGR Docket No. 63230-734.601In some cases, m is selected from 2 to 15. In some cases, m is selected from 2 to 10. In some cases, m is selected from 3 to 30. In some cases, m is selected from 3 to 25. In some cases, m is selected from 3 to 20. In some cases, m is selected from 3 to 15. In some cases, m is selected from 3 to 10. In some cases, m is 1. In some cases, m is 2. In some cases, m is 3. In some cases, m is 4. In some cases, m is 5. In some cases, m is 6. In some cases, m is 7. In some cases, m is 8. In some cases, m is 9. In some cases, m is 10. In some cases, m is 11. In some cases, m is 12. In some cases, m is 13. In some cases, m is 14. In some cases, m is 15. In some cases, m is 16. In some cases, m is 17. In some cases, m is 18. In some cases, m is 19. In some cases, m is 20. In some cases, m is 21. In some cases, m is 22. In some cases, m is 23. In some cases, m is 24. In some cases, m is 25. In some cases, m is less than 35. In some cases, m is less than 30. In some cases, m is less than 25. In some cases, m is less than 20.

[0047] In some embodiments, for a compound or salt of Formula (I), Formula (I- A), Formula (I-B), or Formula (I-C), the compound is selected from:TIPSO TIPSOTIPSOWSGR Docket No. 63230-734.601TIPSO, or a pharmaceutically acceptable salt of any one thereof. In some cases, the compound is selected from:WSGR Docket No. 63230-734.601WSGR Docket No. 63230-734.601TIPSOacceptable salt of any one thereof. In some cases, the compound is selected from:a pharmaceutically acceptable salt of any one thereof.C-C Coupling

[0048] In an aspect, the present disclosure provides a process for the preparation of a compound represented by the structure of Formula (II):comprising a suitable cross-coupling reaction of:WSGR Docket No. 63230-734.601(i) contacting a compound represented by the structure of Formula (II- A) or Formula (II-A*):Formula (II-A*);wherein,each G1is independently a suitable boryl moiety;(ii) with a compound represented by the structure of Formula (II-B):Formula (II-B);wherein,X is a suitable halide;in the presence of a suitable solvent to afford a compound represented by the structure of Formula (II), or a pharmaceutically acceptable salt thereof, wherein: each R1is independently selected from hydrogen, Ci-6 alkyl,, -C(O)R23, and - C(O)OR23;each R2is independently selected from hydrogen, halogen, Ci-6 alkyl, -Si(R20)3, and -B(R21)2;each R3is independently selected from hydrogen and Ci-6 alkyl;each R4is independently selected from hydrogen and Ci-6 alkyl;each R5and R6are independently selected from hydrogen, -Si(R20)3, and Ci-6 alkyl; orone R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl;each R7is independently selected from hydrogen, halogen, Ci-6 alkyl, and -WSGR Docket No. 63230-734.601B(R21)2;each R20is independently selected from Ci-6 alkyl;each R21is independently selected from -OR22;each R22is independently selected from hydrogen and Ci-6 alkyl; or two R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl; each R23is independently selected from Ci-6 alkyl which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, -N(Ci-6alkyl)2, Ci-6 alkyl, -C1-6haloalkyl, and -O-Ci-6 alkyl; andeach m is independently selected from 0 to 20.

[0049] In some embodiments, for a compound or salt of Formula (II), a compound represented by the structure of Formula (II) is prepared from a compound or salt of Formula (II-A) or a compound or salt Formula (II-A*) and a compound or salt of Formula (II-B). In some cases, a compound represented by the structure of Formula (II) is prepared from a compound or salt of Formula (II-A) and a compound or salt of Formula (II-B). In some cases, a compound represented by the structure of Formula (II) is prepared from a compound or salt of Formula (II-A*) and a compound or salt of Formula (II-B). In some cases, the suitable cross-coupling reaction comprises a suitable transition metal complex. In some cases, the suitable transition metal complex comprises a suitable nickel complex, a suitable copper complex, a suitable palladium complex, or suitable combinations thereof. In some cases, the suitable transition metal complex comprises a suitable nickel complex, a suitable copper complex, or a suitable palladium complex. In some cases, the suitable transition metal complex comprises a suitable nickel complex, a suitable palladium complex, or suitable combinations thereof. In some cases, the suitable transition metal complex comprises a suitable nickel complex or a suitable palladium complex. In some cases, the suitable transition metal complex comprises a suitable nickel complex. In some cases, the suitable transition metal complex comprises a suitable palladium complex. In some cases, the suitable palladium complex comprises a suitable palladium precursor and a suitable ligand. In some cases, the suitable palladium precursor is selected from Pd(trifluoroacetate)2, Pd(OAc)2, [Pd(OAc)2]3, PdCh, Pd(PPh3)4, Pd(PPh3)2Cl2, Pd(acac)2, Pd(dibenzylideneacetone)2, Pd2(dibenzylideneacetone)3, allylpalladium chloride dimer, palladium(π-cinnamyl) chloride dimer, Bis(benzonitrile)palladium chloride, and Pd(acetylacetonate)2. In some cases, the suitable palladium precursor is selected fromWSGR Docket No. 63230-734.601Pd(trifluoroacetate)2, Pd(0Ac)2, [Pd(OAc)2]3, PdCl2, Pd(PPh3)4, Pd(PPh3)2Cl2, Pd(dibenzylideneacetone)2, Pd2(dibenzylideneacetone)3, allylpalladium chloride dimer, and palladium(π-cinnamyl) chloride dimer. In some cases, the suitable palladium precursor is selected from Pd(trifluoroacetate)2, Pd(OAc)2, [Pd(OAc)2]3, PdCl2, Pd(dibenzylideneacetone)2, Pd2(dibenzylideneacetone)3, allylpalladium chloride dimer, and palladium(π-cinnamyl) chloride dimer. In some cases, the suitable palladium precursor is selected from Pd(trifluoroacetate)2, Pd(OAc)2, [Pd(OAc)2]3, allylpalladium chloride dimer, and palladium(π-cinnamyl) chloride dimer. In some cases, the suitable palladium precursor is selected from Pd(trifluoroacetate)2, Pd(OAc)2, [Pd(OAc)2]3, and allylpalladium chloride dimer. In some cases, the suitable palladium precursor is selected from Pd(trifluoroacetate)2, Pd(OAc)2, and [Pd(OAc)2]3. In some cases, the suitable palladium precursor is selected from Pd(OAc)2 and [Pd(OAc)2]3. In some cases, the suitable palladium precursor is Pd(OAc)2. In some cases, the suitable ligand is selected from a suitable phosphine ligand. In some cases, the suitable ligand is selected from a suitable monodentate phosphine and a suitable bidentate phosphine. In some cases, the suitable ligand is selected from a suitable monodentate phosphine. In some cases, the suitable monodentate phosphine is selected from a suitable trialkyl-phosphine, a suitable tricycloalkyl-phosphine, a suitable dialkylarylphosphine, a suitable dicycloalkylaryl-phosphine, and a suitable triaryl-phosphine. In some cases, the suitable monodentate phosphine is selected from a suitable trialkyl-phosphine, a suitable tricycloalkyl-phosphine, a suitable dialkylaryl-phosphine, and a suitable dicycloalkylaryl-phosphine. In some cases, the suitable monodentate phosphine is selected from a suitable trialkyl-phosphine and a suitable tricycloalkyl-phosphine. In some cases, the suitable monodentate phosphine is selected from a suitable dialkylaryl-phosphine and a suitable dicycloalkylaryl-phosphine. In some cases, the suitable monodentate phosphine is selected from a suitable dialkylaryl-phosphine. In some cases, the suitable monodentate phosphine is selected from a suitable dicycloalkylaryl-phosphine. In some cases, the suitable monodentate phosphine is selected from a suitable dialkylaryl-phosphine selected from P(Ci-6alkyl)2(C6-i2aryl) and a suitable dicycloalkylaryl-phosphine selected from P(C3-6cycloalkyl)2(C6-i2aryl). In some cases, the suitable monodentate phosphine is selected from a suitable dialkylaryl-phosphine selected from P(Ci-ealkyl Cuaryl) and a suitable dicycloalkylaryl-phosphine selected from P(C3-6cycloalkyl)2(Ci2aryl), wherein each Cuaryl is independently selected fromwhich is optionally substituted with one or more substituents independently selected from CM alkyl and -O-Ci-4 alkyl. In some cases, the suitable monodentate phosphine is a suitable dialkylaryl-phosphine selected from P(Ci-6alkyl)2(C6-i2aryl). In some cases, the suitable monodentateWSGR Docket No. 63230-734.601phosphine is a suitable dialkylaryl-phosphine selected from P(Ci-6alkyl)2(Ci2aryl), wherein Cuarylis selected fromwhich is optionally substituted with one or more substituents independently selected from -N(CM alkyl)2, CM alkyl, -Ci-4haloalkyl, and -O-C1.4 alkyl. In some cases, the suitable monodentate phosphine is a suitable dialkylaryl-phosphine selected from P(Ci-ealkyl Cuaryl), wherein Cuaryl is selected from^— which is optionally substituted with one or more substituents independently selected from CM alkyl and -O-CM alkyl. In some cases, the suitable monodentate phosphine is a suitable dicycloalkylaryl-phosphine selected from P(C3-6cycloalkyl)2(C6-i2aryl). In some cases, the suitable monodentate phosphine is a suitable dicycloalkylaryl-phosphine selected from P(C3-6cycloalkyl)2(Ci2aryl), wherein Cuaryl is selectedfromwhich is optionally substituted with one or more substituents independently selected from -N(CI-4 alkyl)2, CM alkyl, -Ci-4haloalkyl, and -O-C1.4 alkyl. In some cases, the suitable monodentate phosphine is a suitable dicycloalkylaryl-phosphine selected from P(C3-6cycloalkyl)2(Ci2aryl), wherein Cuaryl is selected fromwhich is optionally substituted with one or more substituents independently selected from CM alkyl and -O-C1.4 alkyl.In some cases, Ce-naryl is Cuaryl and Cuaryl is selected fromwhich is optionally substituted with one or more substituents independently selected from -N(CM alkyl)2, CM alkyl, -CM haloalkyl, and -O-C1.4 alkyl. In some cases, Ce-uaryl is Cuaryl and Cuaryl isselected from, which is optionally substituted with one or more substituents independently selected from CM alkyl and -O-CM alkyl. In some cases, the suitable dialkylaryl-phosphine and the suitable dicycloalkylaryl-phosphine is selected from SPhos, XPhos, MePhos, tBuMePhos, t-BuDavePhos, DavePhos, CyJohnPhos, JohnPhos, RuPhos, and suitable combinations thereof. In some cases, the suitable dialkylaryl-phosphine and the suitable dicycloalkylaryl-phosphine is selected from SPhos, XPhos, MePhos, tBuMePhos, t-BuDavePhos, DavePhos, CyJohnPhos, JohnPhos, and RuPhos. In some cases, the suitable dialkylaryl-WSGR Docket No. 63230-734.601phosphine is selected from tBuMePhos, t-BuDavePhos, JohnPhos, and suitable combinations thereof. In some cases, the suitable dialkylaryl-phosphine is selected from tBuMePhos, t-BuDavePhos, and JohnPhos. In some cases, the suitable dicycloalkylaryl-phosphine is selected from SPhos, XPhos, MePhos, DavePhos, CyJohnPhos, RuPhos, and suitable combinations thereof. In some cases, the suitable dicycloalkylaryl-phosphine is selected from SPhos, XPhos, MePhos, DavePhos, CyJohnPhos, and RuPhos. In some cases, the suitable dicycloalkylaryl-phosphine is selected from SPhos, XPhos, MePhos, and RuPhos. In some cases, the suitable dicycloalkylaryl-phosphine is selected from SPhos, XPhos, and RuPhos. In some cases, the suitable dicycloalkylaryl-phosphine is selected from SPhos, RuPhos, and suitable combinations thereof. In some cases, the suitable dicycloalkylaryl-phosphine is selected from SPhos and RuPhos. In some cases, the suitable dicycloalkylaryl-phosphine is SPhos. In some cases, the suitable palladium complex comprises Pd(OAc)2 and a suitable dialkylaryl-phosphine selected from tBuMePhos, t-BuDavePhos, and JohnPhos. In some cases, the suitable palladium complex comprises Pd(OAc)2 and a suitable dicycloalkylaryl-phosphine selected from SPhos, XPhos, MePhos, DavePhos, CyJohnPhos, and RuPhos. In some cases, the suitable palladium complex comprises [Pd(OAc)2]3 and a suitable dialkylaryl-phosphine selected from tBuMePhos, t-BuDavePhos, and JohnPhos. In some cases, the suitable palladium complex comprises [Pd(OAc)2]3 and a suitable dicycloalkylaryl-phosphine selected from SPhos, XPhos, MePhos, DavePhos, CyJohnPhos, and RuPhos. In some cases, the suitable palladium complex comprises Pd(OAc)2 and a suitable dicycloalkylaryl-phosphine selected from SPhos, XPhos, and RuPhos. In some cases, the suitable palladium complex comprises [Pd(OAc)2]3 and a suitable dicycloalkylaryl-phosphine selected from SPhos, XPhos, and RuPhos. In some cases, the suitable palladium complex comprises Pd(OAc)2 and a suitable dicycloalkylaryl-phosphine selected from SPhos and RuPhos. In some cases, the suitable palladium complex comprises [Pd(OAc)2]3 and a suitable dicycloalkylaryl-phosphine selected from SPhos and RuPhos. In some cases, the suitable palladium complex comprises [Pd(OAc)2]3 and SPhos. In some cases, the suitable palladium complex comprises Pd(OAc)2 and SPhos. In some cases, the suitable palladium complex comprises Pd(OAc)2 and a dialkylaryl-phosphine selected from P(Ci-6alkyl)2(Ci2aryl) or a dicycloalkylaryl-phosphine selected from P(C3-6cycloalkyl)2(Ci2aryl), wherein each Cuaryl isindependently selected fromwhich is optionally substituted with one or more substituents independently selected from CM alkyl and -O-C1.4 alkyl. In some cases, the suitable palladium complex comprises Pd(OAc)2 and a dialkylaryl-phosphine selected from P(Ci-WSGR Docket No. 63230-734.601ealkyl Cuaryl), wherein Cuaryl is selected from" — " —J ' which is optionally substituted with one or more substituents independently selected from CM alkyl and -O-C1.4 alkyl. In some cases, the suitable palladium complex comprises Pd(OAc)2 and a dicycloalkylaryl-phosphineselected from P(C3-6cycloalkyl)2(Ci2aryl), wherein Cuaryl is selected from— 'J which is optionally substituted with one or more substituents independently selected from CM alkyl and -O-Ci-4 alkyl. In some cases, the suitable palladium complex comprises [Pd(OAc)2]3 and a dialkylaryl-phosphine selected from P(Ci-6alkyl)2(Ci2aryl) or a dicycloalkylaryl-phosphine selected from P(C3-6cycloalkyl)2(Cuaryl), wherein each Cuaryl is independently selected fromwhich is optionally substituted with one or more substituents independently selected from Ci-4 alkyl and -O-C1.4 alkyl. In some cases, the suitable palladium complex comprises [Pd(OAc)2]3 and a di alkyl aryl -phosphine selected from P(Ci-6alkyl)2(Ci2aryl), whereinCuaryl is selected fromwhich is optionally substituted with one or more substituents independently selected from CM alkyl and -O-C1.4 alkyl. In some cases, the suitable palladium complex comprises [Pd(OAc)2]3 and a dicycloalkylaryl-phosphine selected from P(C3-6cycloalkyl)2(Ci2aryl), wherein Cuaryl is selected fromv — 'J v — 'J which is optionally substituted with one or more substituents independently selected from CM alkyl and -O-Ci-4 alkyl.

[0050] In some embodiments, for a compound or salt of Formula (II-A) or Formula (II-A*), each G1is independently selected from -B(R21a)2, wherein: each R21ais independently selected from -OR22a; and each R22ais independently selected from hydrogen and Ci-6 alkyl; or two R22aon different O atoms are taken together with the O atom to which each R22ais attached to form a heterocycle which is optionally substituted with one or more substituents independently selected from CMO alkyl. In some cases, each G1is independently selected from -B(R21a)2, wherein: each R21ais independently selected from -OR22a; each R22ais independently selected from hydrogen, -CH3, -CH2CH3, and -CH(CH3)2; or two R22aon different O atoms are taken together with the O atom to which each R22ais attached to form a heterocycle which is optionallyWSGR Docket No. 63230-734.601substituted with one or more substituents independently selected from Ci-6 alkyl. In some cases, each G1is independently selected from -B(R21a)2, wherein: each R21ais independently selected from -OR22a; each R22ais independently selected from hydrogen, -CH3, -CH2CH3, and -CH(CH3)2; or two R22aon different O atoms are taken together with the O atom to which each R22ais attached to form a 5- to 6-membered heterocycle which is optionally substituted with one or more substituents independently selected from Ci-6 alkyl. In some cases, each G1is independently selected from -B(R21a)2, wherein: each R21ais independently selected from -OR22a; and each R22ais independently selected from hydrogen, -CH3, -CH2CH3, and -CH(CH3)2; or two R22aon different O atoms are taken together with the O atom to which each R22ais attached to form a heterocycle which is optionally substituted with one or more substituents independently selected from C1-4 alkyl. In some cases, each G1is independently selected from -B(R21a)2, wherein: each R21ais independently selected from -OR22a; and each R22ais independently selected from hydrogen, -CH3, and -CH(CH3)2; or two R22aon different O atoms are taken together with the O atom to which each R22ais attached to form a heterocycle which is optionally substituted with one or more substituents independently selected from C1-4 alkyl. In some cases, each G1is independently selected from -B(R21a)2, wherein: each R21ais independently selected from -OR22a; and each R22ais independently selected from hydrogen, -CH3, and -CH(CH3)2; or two R22aon different O atoms are taken together with the O atom to which each R22ais attached to form a 5- to 6-membered heterocycle which is optionally substituted with one or more substituents independently selected from CM alkyl. In some cases, each G1is independently selected from -B(R21a)2, wherein: each R21ais independently selected from -OR22a; and each R22ais independently selected from hydrogen; or two R22aon different O atoms are taken together with the O atom to which each R22ais attached to form a heterocycle which is optionally substituted with one or more substituents independently selected from C1.4 alkyl. In some cases, each G1is independently selected from -B(R21a)2, wherein: each R21ais independently selected from -OR22a; and each R22ais independently selected from hydrogen; or two R22aon different O atoms are taken together with the O atom to which each R22ais attached to form a 5- to 6-membered heterocycle which is optionally substituted with one or more substituents independently selected from C1-4 alkyl. In some cases, each G1is independently selected from -B(R21a)2, wherein: each R21ais independently selected from -OR22a; and two R22aon different O atoms are taken together with the O atom to which each R22ais attached to form a heterocycle, which is optionally substituted with one or more substituents independently selected from C1-4alkyl. In some cases, each G1is independently selected from -B(R21a)2, wherein: each R21ais independently selected from -OR22a; and two R22aon different O atoms are taken together with the O atom to which each R22ais attached to form a 5- to 6-membered heterocycle, which isWSGR Docket No. 63230-734.601optionally substituted with one or more substituents independently selected from CM alkyl. In some cases, each G1is independently selected from -B(R21a)2, wherein: each R21ais independently selected from -OR22a; and two R22aon different O atoms are taken together with the O atom to which each R22ais attached to form a heterocycle, which is optionally substituted with one or more substituents independently selected from -CH3 and -CH2CH3. In some cases, each G1is independently selected from -B(R21a)2, wherein: each R21ais independently selected from -OR22a; and two R22aon different O atoms are taken together with the O atom to which each R22ais attached to form a 5- to 6-membered heterocycle, which is optionally substituted with one or more substituents independently selected from -CH3 and -CH2CH3. In some cases, each G1is independently selected from -B(R21a)2, wherein: each R21ais independently selected from -OR22a; and two R22aon different O atoms are taken together with the O atom to which each R22ais attached to form a heterocycle, which is optionally substituted with one or more substituents independently selected from -CH3. In some cases, each G1is independently selected from -B(R21a)2, wherein: each R21ais independently selected from -OR22a; and two R22aon different O atoms are taken together with the O atom to which each R22ais attached to form a 5- to 6-membered heterocycle, which is optionally substituted with one or more substituents independently selected from -CH3. In some cases, G1is selected from -B(OH)2, -B(OMe)2, -B(OiPr)2, -Bpin, and -Bneop. In some cases, GHs selected from -B(OH)2, -Bpin, and -Bneop. In some cases, G1is selected from -Bpin and -Bneop. In some cases, G1moiety is -Bpin. In some cases, G1is -Bneop.

[0051] In some embodiments, for a compound or salt of Formula (II), a compound represented by the structure of Formula (II) is prepared from a compound or salt of Formula (II-A) or a compound or salt Formula (II-A*) and a compound or salt of Formula (II-B). In some cases, a compound represented by the structure of Formula (II) is prepared from a compound or salt of Formula (II-A) and a compound or salt of Formula (II-B). In some cases, a compound represented by the structure of Formula (II) is prepared from a compound or salt Formula (II-A*) and a compound or salt of Formula (II-B). In some cases, the suitable solvent is selected from toluene, benzene, THF, 1,4-di oxane, DMA, DMF, DMSO, MeCN, water, and suitable combinations thereof. In some cases, the suitable solvent is selected from toluene, benzene, THF, 1,4-di oxane, MeCN, water, and suitable combinations thereof. In some cases, the suitable solvent is selected from toluene, THF, 1,4-di oxane, water, and suitable combinations thereof. In some cases, the suitable solvent is selected from THF, 1,4-dioxane, water, and suitable combinations thereof. In some cases, the suitable solvent is selected from THF, water, and suitable combinations thereof. In some cases, the suitable solvent is a combination of THF and water. InWSGR Docket No. 63230-734.601some cases, the suitable solvent is a combination of 1,4-di oxane and water.

[0052] In some embodiments, for a compound or salt of Formula (II-B), X is selected from a halogen. In some cases, X is selected from fluoro, chloro, bromo, and iodo. In some cases, X is selected from fluoro and chloro. In some cases, X is chloro. In some cases, X is fluoro. In some cases, X is selected from chloro, bromo, and iodo. In some cases, X is selected from bromo and iodo. In some cases, X is iodo. In some cases, X is bromo.Desilylation

[0053] In an aspect, the present disclosure provides a process for the preparation of a compound represented by the structure of Formula (III) orFormula (III*):comprising a suitable desilylation reaction of:(i) contacting a compound represented by the structure of Formula (III-A) or Formula (III-A*):Formula (III-A*); wherein,each G2is independently a suitable silyl moiety;(ii) with a suitable desilylation reagent,WSGR Docket No. 63230-734.601in the presence of a suitable solvent to afford a compound represented by the structure of Formula (III) or Formula (III*), or a pharmaceutically acceptable salt of any one thereof, wherein:each R1is independently selected from hydrogen, Ci-6 alkyl,, -C(O)R23, and - C(O)OR23;each R2is independently selected from hydrogen, halogen, Ci-6 alkyl, -Si(R20)3, and -B(R21)2;each R3is independently selected from hydrogen and Ci-6 alkyl;each R4is independently selected from hydrogen and Ci-6 alkyl;each R5and R6are independently selected from hydrogen, -Si(R20)3, and Ci-6 alkyl; orone R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl;each R7is independently selected from hydrogen, halogen, Ci-6 alkyl, and - B(R21)2;each R20is independently selected from Ci-6 alkyl;each R21is independently selected from -OR22;each R22is independently selected from hydrogen and Ci-6 alkyl; or two R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl;each R23is independently selected from Ci-6 alkyl which is optionally substituted with one or more substituents independently selected from halogen, -OH, - CN, -NO2, -NH2, -N(CI-6 alkyl)2, Ci-6 alkyl, -C1-6haloalkyl, and -O-Ci-6 alkyl; andeach m is independently selected from 0 to 20.

[0054] In some embodiments, for a compound or salt of Formula (III) or Formula (III*), a compound represented by the structure of Formula (III) or Formula (III*) is prepared from a compound or salt of Formula (III- A) or a compound or salt Formula (III- A*). In some cases, a compound represented by the structure of Formula (III) is prepared from a compound or salt of Formula (III-A). In some cases, a compound represented by the structure of Formula (III*) is prepared from a compound or salt Formula (III-A*). In some cases, the suitable desilylation reagent is a suitable acid or a suitable fluoride reagent. In some cases, wherein the suitableWSGR Docket No. 63230-734.601desilylation reagent is a suitable acid. In some cases, the suitable acid is a suitable organic acid or a suitable inorganic acid. In some cases, the suitable inorganic acid is selected from HF, HC1, HBr, and HI. In some cases, the suitable inorganic acid is selected from HF, HC1, and HBr. In some cases, the suitable inorganic acid is selected from HF and HC1. In some cases, the suitable inorganic acid is selected from HF. In some cases, the suitable organic acid is selected from Pyridinium p-toluenesulfonate (PPTS), tetrabutyl ammonium p-toluenesulfonate, acetic acid, trifluoroacetic acid, oxalic acid, critic acid, butyric acid, malic acid, and formic acid. In some cases, the suitable organic acid is selected from Pyridinium p-toluenesulfonate (PPTS), tetrabutylammonium p-toluenesulfonate, acetic acid, and trifluoroacetic acid. In some cases, wherein the suitable organic acid is Pyridinium p-toluenesulfonate (PPTS). In some cases, the suitable organic acid is tetrabutyl ammonium p-toluenesulfonate. In some cases, the suitable organic acid is acetic acid. In some cases, the suitable organic acid is trifluoroacetic acid. In some cases, the suitable desilylation reagent is a suitable fluoride reagent. In some cases, the suitable fluoride reagent is selected from tetrabutyl ammonium fluoride, LiF, NaF, KF, CsF, and RbF. In some cases, the suitable fluoride reagent is selected from tetrabutyl ammonium fluoride, NaF, KF, and CsF. In some cases, the suitable fluoride reagent is selected from tetrabutylammonium fluoride, KF, and CsF. In some cases, the suitable fluoride reagent is tetrabutyl ammonium fluoride. In some cases, the suitable fluoride reagent further comprises a suitable crown ether. In some cases. The suitable fluoride reagent further comprises 18-Crown-6. In some cases, the suitable crown ether is 18 -Crown-6.

[0055] In some embodiments, for a compound or salt of Formula (III-A) or Formula (III-A*), G2is selected from -Si(R20b)3, wherein each R20bis independently selected from Ci-6 alkyl. In some cases, G2is selected from -Si(Ci-6alkyl)3. In some cases, G2is selected from -Si(Me)3, -Si(Et)3, -Si(nbutyl)3, -Si(nhexyl)3, and -Si(1Pr)3. In some cases, G2is selected from -Si(Me)3, -Si(Et)3, and -Si(1Pr)3. In some cases, G2is selected from -Si(Me)3 and -Si(Et)3. In some cases, G2is -Si(Et)3. In some cases, G2is -Si(Me)3. In some cases, G2is -Si(1Pr)3.

[0056] In some embodiments, for a compound or salt of Formula (III) or Formula (III*), a compound represented by the structure of Formula (III) or Formula (III*) is prepared from a compound or salt of Formula (III-A) or a compound or salt Formula (III-A*). In some cases, a compound represented by the structure of Formula (III) is prepared from a compound or salt of Formula (III-A). In some cases, a compound represented by the structure of Formula (III*) is prepared from a compound or salt Formula (III-A*). In some cases, the suitable solvent is selected from MeOH, EtOH, 'PrOH, 'BuOH, THF, 1,4-di oxane, MeCN, water, DMA, DMSO, DMAc, and suitable combinations thereof. In some cases, the suitable solvent is selected fromWSGR Docket No. 63230-734.601MeOH, EtOH, THF, 1,4-dioxane, MeCN, water, DMA, DMSO, DMAc, and suitable combinations thereof. In some cases, the suitable solvent is selected from MeOH, EtOH, THF, 1,4-di oxane, MeCN, DMA, DMSO, and DMAc. In some cases, the suitable solvent is selected from MeOH, EtOH, 'PrOH, THF, 1,4-di oxane, MeCN, water, and suitable combinations thereof. In some cases, the suitable solvent is selected from MeOH, EtOH, THF, 1,4-di oxane, MeCN, water, and suitable combinations thereof. In some cases, the suitable solvent is selected from MeOH, EtOH, THF, 1,4-dioxane, and MeCN. In some cases, the suitable solvent is selected from MeOH, EtOH, THF, 1,4-dioxane, water, and suitable combinations thereof. In some cases, the suitable solvent is selected from MeOH, EtOH, THF, and 1,4-dioxane. In some cases, the suitable solvent is selected from MeOH, THF, 1,4-dioxane, water, and suitable combinations thereof. In some cases, the suitable solvent is selected from MeOH, 1,4-dioxane, water, and suitable combinations thereof. In some cases, the suitable solvent is selected from MeOH, THF, and suitable combinations thereof. In some cases, the suitable solvent is MeOH. In some cases, the suitable solvent is THF. In some cases, the suitable solvent is a combination of MeOH and THF. In some cases, the suitable solvent is selected from MeOH, 1,4-dioxane, and suitable combinations thereof. In some cases, the suitable solvent is 1,4-dioxane. In some cases, the suitable solvent is a combination of MeOH and 1,4-dioxane.Borylation

[0057] In an aspect, the present disclosure provides a process for the preparation of a compound represented by the structure of Formula (IV) or Formula (IV*):R6O R7comprising a suitable borylation reaction of:(i) contacting a compound represented by the structure of Formula (IV-A) or Formula (IV- A*):WSGR Docket No. 63230-734.601R6O R7OR6OR5R6O R7R5O R1Formula (IV-A) or Formula (IV-A*); (ii) with a suitable borylation reagent,in the presence of a suitable solvent to afford a compound represented by the structure of Formula (IV) or Formula (IV*), or a pharmaceutically acceptable salt of any one thereof, wherein:each R1is independently selected from hydrogen, Ci-6 alkyl, -C(O)R23, and -C(O)OR23; each R2is independently selected from hydrogen, halogen, Ci-6 alkyl, -Si(R20)3, and - B(R21)2;each R3is independently selected from hydrogen and Ci-6 alkyl;each R4is independently selected from hydrogen and Ci-6 alkyl;each R5and R6are independently selected from hydrogen, -Si(R20)3, and Ci-6 alkyl; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl; each R7is independently selected from hydrogen, halogen, Ci-6 alkyl, and -B(R21)2; each R20is independently selected from Ci-6 alkyl;each R21is independently selected from -OR22;each R22is independently selected from hydrogen and Ci-6 alkyl; ortwo R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl;each R23is independently selected from Ci-6 alkyl which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, - NH2, -N(Ci-6alkyl)2, Ci-6 alkyl, -C1-6haloalkyl, and -O-Ci-6 alkyl; and each m is independently selected from 0 to 20.

[0058] In some embodiments, for a compound or salt of Formula (IV) or Formula (IV*), a compound represented by the structure of Formula (IV) or Formula (IV*) is prepared from aWSGR Docket No. 63230-734.601compound or salt of Formula (IV-A) or a compound or salt Formula (IV-A*). In some cases, a compound represented by the structure of Formula (IV) is prepared from a compound or salt of Formula (IV-A). In some cases, a compound represented by the structure of Formula (IV*) is prepared from a compound or salt Formula (IV-A*). In some cases, the suitable borylation reaction comprises a suitable transition metal complex. In some cases, the suitable transition metal complex comprises a suitable rhodium complex, a suitable iridium complex, a suitable iron complex, or suitable combinations thereof. In some cases, the suitable transition metal complex comprises a suitable rhodium complex, a suitable iridium complex, or a suitable iron complex. In some cases, the suitable transition metal complex comprises a suitable rhodium complex or a suitable iridium complex. In some cases, the suitable transition metal complex comprises a suitable iridium complex or a suitable iron complex. In some cases, the suitable transition metal complex comprises a suitable rhodium complex. In some cases, the suitable transition metal complex comprises a suitable iron complex. In some cases, the transition metal complex comprises a suitable iridium complex. In some cases, the suitable iridium complex comprises a suitable iridium precursor and a suitable ligand. In some cases, the suitable iridium precursor is selected (l,5-cyclooctadiene)(methoxy)iridium dimer, (l,5-cyclooctadiene)(chloro)iridium dimer, [(MeCN)2(l,5-cyclooctadiene)iridium]BF4, and 1,5-Cyclooctadiene(acetylacetonato)iridium. In some cases, the suitable iridium precursor is selected (l,5-cyclooctadiene)(methoxy)iridium dimer, (l,5-cyclooctadiene)(chloro)iridium dimer, and 1,5-Cyclooctadiene(acetylacetonato)iridium. In some cases, the suitable iridium precursor is selected (l,5-cyclooctadiene)(methoxy)iridium dimer and (l,5-cyclooctadiene)(chloro)iridium dimer. In some cases, the suitable iridium precursor is (l,5-cyclooctadiene)(chloro)iridium dimer. In some cases, the suitable iridium precursor is 1,5-Cyclooctadiene(acetylacetonato)iridium. In some cases, the suitable iridium precursor is (l,5-cyclooctadiene)(methoxy)iridium dimer. In some cases, the suitable ligand is selected from a suitable pyridine, a suitable bipyridine, and a suitable phenanthroline. In some cases, the suitable ligand is selected from a suitable bipyridine and a suitable phenanthroline. In some cases, the suitable ligand is selected from a suitable phenanthroline. In some cases, the suitable ligand is selected from a suitable bipyridine. In some cases, the suitable ligand is selected from bipyridine, 4,4'di- / c / 7-butyl-2,2'- bipyridine (dtbpy), 4,4'-dimethoxy-2-2'-bipyridine (4,4’-OMebpy), 4,4'-dimethylamino-2-2'-bipyridine (4,4’-NMe2bpy), 4,4'-ditrifhroromethyl-2-2'-bipyridine (4,4’-CF3bpy), 4,4'-diphenyl-2-2'-bipyridine (4,4’-Phbpy), and 4,4'-dimethyl-2,2'- bipyridine (4,4’-Mebpy). In some cases, the suitable ligand is selected from 4,4'di-tert-butyl-2,2'- bipyridine (dtbpy), 4,4'-dimethoxy-2-2'-bipyridine (4,4’-OMebpy), 4,4'-dimethylamino-2-2'-bipyridine (4,4’-NMe2bpy), and 4,4 '-dimethyl -2, 2'- bipyridineWSGR Docket No. 63230-734.601(4,4’-Mebpy). In some cases, the suitable ligand is selected from 4,4'di- / c / 7-butyl-2,2'- bipyridine (dtbpy), 4,4'-dimethoxy-2-2'-bipyridine (4,4’-OMebpy), and 4,4'-dimethyl-2,2'- bipyridine (4,4’-Mebpy). In some cases, the suitable ligand is selected from 4,4'di-tert-butyl-2,2'- bipyridine (dtbpy) and 4,4'-dimethoxy-2-2'-bipyridine (4,4’-OMebpy). In some cases, the suitable ligand is 4,4'-dimethoxy-2-2'-bipyridine (4,4’-Omebpy). In some cases, the suitable ligand is 4,4'-dimethoxy-2-2'-bipyridine (4,4’-Omebpy). In some cases, the suitable ligand is 4,4'-dimethyl-2,2'- bipyridine (4,4’-Mebpy). In some cases, wherein the suitable ligand is 4,4'di-tert-butyl-2,2'-bipyridine (dtbpy). In some cases, the suitable iridium complex comprises (1,5-cyclooctadiene)(methoxy)iridium dimer and a suitable bipyridine selected 4,4'di-tert-butyl-2,2'-bipyridine (dtbpy), 4,4'-dimethoxy-2-2'-bipyridine (4,4’-OMebpy), and 4,4'-dimethyl-2,2'-bipyridine (4,4’-Mebpy). In some cases, the suitable iridium complex comprises (1,5-cyclooctadiene)(methoxy)iridium dimer and 4,4'di- / c 7-butyl-2,2'- bipyridine (dtbpy). In some cases, the suitable iridium complex comprises (l,5-cyclooctadiene)(chloro)iridium dimer and 4,4'di- / c 7-butyl-2,2'- bipyridine (dtbpy). In some cases, the suitable iridium complex comprises (l,5-cyclooctadiene)(chloro)iridium dimer and a suitable bipyridine selected 4,4'di-tert-butyl-2,2'-bipyridine (dtbpy), 4,4'-dimethoxy-2-2'-bipyridine (4,4’-OMebpy), and 4,4'-dimethyl-2,2'-bipyridine (4,4’-Mebpy).

[0059] In some embodiments, for a compound or salt of Formula (IV) or Formula (IV*), a compound represented by the structure of Formula (IV) or Formula (IV*) is prepared from a compound or salt of Formula (IV-A) or a compound or salt Formula (IV-A*). In some cases, a compound represented by the structure of Formula (IV) is prepared from a compound or salt of Formula (IV-A). In some cases, a compound represented by the structure of Formula (IV*) is prepared from a compound or salt Formula (IV-A*). In some cases, the suitable borylation reagent is selected from bis(catecholato)diboron (B2Cat2), bis(neopentyl glycolato)diboron (B2neop2), bis(pinacolato)diboron (B2pin2), Catecholborane (HBcat), 4,4,5,5-Tetramethyl-l,3,2-dioxaborolane (HBpin). In some cases, the suitable borylation reagent is selected from bis(neopentyl glycolato)diboron (B2neop2), bis(pinacolato)diboron (B2pin2), and 4, 4,5,5-Tetramethyl-l,3,2-dioxaborolane (HBpin). In some cases, the suitable borylation reagent is selected from bis(neopentyl glycolato)diboron (B2neop2) and bis(pinacolato)diboron (B2pin2). In some cases, the suitable borylation reagent is selected from bis(pinacolato)diboron (B2pin2) and 4,4,5,5-Tetramethyl-l,3,2-dioxaborolane (HBpin). In some cases, the suitable borylation reagent is bis(pinacolato)diboron (B2pin2). In some cases, the suitable borylation reagent is bis(neopentyl glycol ato)diboron (B2neop2). In some cases, the suitable borylation reagent is 4, 4,5,5-Tetramethyl-l,3,2-dioxaborolane (HBpin).WSGR Docket No. 63230-734.601

[0060] In some embodiments, for a compound or salt of Formula (IV) or Formula (IV*), a compound represented by the structure of Formula (IV) or Formula (IV*) is prepared from a compound or salt of Formula (IV-A) or a compound or salt Formula (IV-A*). In some cases, a compound represented by the structure of Formula (IV) is prepared from a compound or salt of Formula (IV-A). In some cases, a compound represented by the structure of Formula (IV*) is prepared from a compound or salt Formula (IV-A*). In some cases, suitable solvent is selected from benzene, cyclohexane, hexane, heptane, octane, THF, 1,4-di oxane, and suitable combinations thereof. In some cases, suitable solvent is selected from benzene, cyclohexane, hexane, heptane, octane, and THF, and 1,4-di oxane. In some cases, suitable solvent is selected from cyclohexane, hexane, heptane, octane, THF, and 1,4-di oxane. In some cases, suitable solvent is selected from cyclohexane, hexane, heptane, octane, and THF. In some cases, suitable solvent is selected from cyclohexane, THF, 1,4-di oxane, and suitable combinations thereof. In some cases, suitable solvent is selected from cyclohexane, THF, and 1,4-di oxane. In some cases, suitable solvent is selected from benzene, THF, 1,4-di oxane, and suitable combinations thereof. In some cases, suitable solvent is selected from benzene, THF, and 1,4-di oxane. In some cases, suitable solvent is selected from cyclohexane and THF. In some cases, suitable solvent is selected from THF and 1,4-dioxane. In some cases, the suitable solvent is THF. In some cases, suitable solvent is cyclohexane.

[0061] In some embodiments, for a compound or salt of Formula (II), Formula (II- A), Formula (II-A*), Formula (II-B), Formula (III), Formula (III*), Formula (III-A), Formula (III-A*), Formula (IV), Formula (IV*), Formula (IV-A), Formula (IV-A*), each R1is independently selected from hydrogen, Ci-6 alkyl, -C(O)R23, and -C(O)OR23. In some cases, each R1is independently selected from hydrogen, -CH3, -CH2CH3, -CH(CH3)2, -CH2CH2CH3, -C(CH3)3, -CH2CH2CH2CH3, -C(O)R23, and -C(O)OR23. In some cases, each R1is independently selected from hydrogen, -CH3, -CH2CH3, -CH(CH3)2, -C(O)R23, and -C(O)OR23. In some cases, each R1is independently selected from hydrogen, -CH3, -CH2CH3, -C(O)R23, and -C(O)OR23. In some cases, each R1is independently selected from hydrogen, -C(O)R23, and -C(O)OR23. In some cases, each R1is independently selected from hydrogen, -C(O)CH3, -C(O)C(CH3)3, and -C(O)OR23. In some cases, each R1is independently selected from hydrogen and -C(O)OR23. In some cases, each R1is independently selected from hydrogen, -C(O)OCH3, -C(O)OCH(CH3)2, and -C(O)OC(CH3)3. In some cases, each R1is independently selected from hydrogen, -C(O)OCH3, and -C(O)OC(CH3)3. In some cases, each R1is independently selected from hydrogen and -C(O)OC(CH3)3. In some cases, each R1is independently selected from hydrogen. In some cases, R1is hydrogen. In some cases, R1is -C(O)OC(CH3)3.WSGR Docket No. 63230-734.601

[0062] In some embodiments, for a compound or salt of Formula (II), Formula (II-B), Formula (III), Formula (III*), Formula (IV), Formula (IV*), each R2is independently selected from hydrogen, halogen, Ci-6 alkyl, -Si(R20)3, and -B(R21)2. In some cases, each R2is independently selected from hydrogen, Ci-6 alkyl, -Si(R20)3, and -B(R21)2. In some cases, eachR2is independently selected from hydrogen, -CH3, -CH2CH3, -CH(CH3)2, -CH2CH2CH3, -C(CH3)3, -Si(R20)3, and -B(R21)2. In some cases, each R2is independently selected from hydrogen, -CH3, -CH2CH3, -Si(R20)3, and -B(R21)2. In some cases, each R2is independently selected from hydrogen, -Si(R20)3, and -B(R21)2. In some cases, each R2is independently selected from hydrogen, -Si(Me)3, -Si(Et)3, -Si(iPr)3, -Si(nButyl)3, -Si(OMe)3, -Si(OEt)3, -Si(iPr)3, Si(OnButyl)3, -B(OH)2, -B(OMe)2, -B(O1Pr)2, -Bpin, -Bneop, and -Beat. In some cases, each R2is independently selected from hydrogen, -Si(Me)3, -Si(Et)3, -Si(nButyl)3, -B(OH)2, -B(OMe)2, -B(O1Pr)2, -Bpin, and -Bneop. In some cases, each R2is independently selected from hydrogen, -Si(Me)3, -Si(Et)3, -B(OMe)2, -B(O1Pr)2, -Bpin, and -Bneop. In some cases, each R2is independently selected from hydrogen, -Si(Me)3, -Si(Et)3, -Bpin, and -Bneop. In some cases, each R2is independently selected from hydrogen, -Si(Me)3, -Bpin, and -Bneop. In some cases, each R2is independently selected from hydrogen, -Si(Me)3, and -Bpin. In some cases, each R2is independently selected from -Si(Me)3 and -Bpin. In some cases, each R2is independently selected from hydrogen and -Bpin. In some cases, each R2is independently selected from hydrogen and -Si(Me)3. In some cases, each R2is independently selected from -Bpin. In some cases, each R2is independently selected from hydrogen. In some cases, each R2is independently selected from -Si(Me)3.

[0063] In some embodiments, for a compound or salt of Formula (II), Formula (II- A), Formula (II-A*), Formula (II-B), Formula (III), Formula (III*), Formula (III-A), Formula (III-A*), Formula (IV), Formula (IV*), Formula (IV-A), Formula (IV-A*), each R3is independently selected from hydrogen and Ci-6 alkyl. In some cases, each R3is independently selected from hydrogen and C1-4 alkyl. In some cases, each R3is independently selected from hydrogen, -CH3, -CH2CH3, -CH(CH3)2, -CH2CH2CH3, and -C(CH3)3. In some cases, each R3is independently selected from hydrogen, -CH3, -CH2CH3, -CH(CEE)2, and -CH2CH2CH3. In some cases, each R3is independently selected from hydrogen, -CH3, -CH2CH3, and -CH2CH2CH3. In some cases, each R3is independently selected from hydrogen, -CH3, and -CH2CH3. In some cases, each R3is independently selected from hydrogen and -CH3. In some cases, each R3is independently selected from hydrogen.

[0064] In some embodiments, for a compound or salt of Formula (II), Formula (II-A), Formula (II-A*), Formula (II-B), Formula (III), Formula (III*), Formula (III-A), Formula (III-A*), Formula (IV), Formula (IV*), Formula (IV-A), Formula (IV-A*), each R4is independentlyWSGR Docket No. 63230-734.601selected from hydrogen and Ci-6 alkyl. In some cases, each R4is independently selected from hydrogen and Ci-4 alkyl. In some cases, each R4is independently selected from hydrogen, -CH3, -CH2CH3, -CH(CH3)2, -CH2CH2CH3, and -C(CH3)3. In some cases, each R4is independently selected from hydrogen, -CH3, -CH2CH3, -CH(CH3)2, and -CH2CH2CH3. In some cases, each R4is independently selected from hydrogen, -CH3, -CH2CH3, and -CH2CH2CH3. In some cases, each R4is independently selected from hydrogen, -CH3, and -CH2CH3. In some cases, each R4is independently selected from hydrogen and -CH3. In some cases, each R4is independently selected from hydrogen.

[0065] In some embodiments, for a compound or salt of Formula (II), Formula (II- A), Formula (II-A*), Formula (III), Formula (III*), Formula (III-A), Formula (III-A*), Formula (IV), Formula (IV*), Formula (IV-A), Formula (IV-A*), each R7is selected from hydrogen, halogen, Ci-6 alkyl, and -B(R21)2. In some cases, each R7is selected from hydrogen, halogen, C1-4 alkyl, and -B(R21)2. In some cases, each R7is selected from hydrogen, halogen, -CH3, -CH2CH3, -CH(CH3)2, -CH2CH2CH3, -C(CH3)3, and -B(R21)2. In some cases, each R7is selected from hydrogen, halogen, -CH3, -CH2CH3, -CH(CH3)2, and -B(R21)2. In some cases, each R7is selected from hydrogen, halogen, and -B(R21)2. In some cases, each R7is selected from hydrogen, halogen, -B(OH)2, -B(OMe)2, -B(O1Pr)2, -Bpin, -Bneop, and -Beat. In some cases, each R7is selected from hydrogen, halogen, -B(OH)2, -B(OMe)2, -B^Pr^, -Bpin, and -Bneop. In some cases, each R7is selected from hydrogen, halogen, -B(OH)2, -Bpin, and -Bneop. In some cases, each R7is selected from hydrogen, halogen, -Bpin, and -Bneop. In some cases, each R7is selected from hydrogen, halogen, and -Bpin. In some cases, each R7is selected from hydrogen, bromo, iodo, and -B(R21)2. In some cases, each R7is selected from hydrogen, bromo, iodo, -B(OH)2, -B(OMe)2, -B(O1Pr)2, -Bpin, -Bneop, and -Beat. In some cases, each R7is selected from hydrogen, bromo, iodo, -B(OH)2, -B(OMe)2, -B(O1Pr)2, -Bpin, and -Bneop. In some cases, each R7is selected from hydrogen, bromo, iodo, -B(OH)2, -Bpin, and -Bneop. In some cases, each R7is selected from hydrogen, bromo, iodo, -Bpin, and -Bneop. In some cases, each R7is selected from hydrogen, bromo, iodo, and -Bpin. In some cases, each R7is selected from hydrogen, iodo, -B(R21)2. In some cases, each R7is selected from hydrogen, iodo, -B(OH)2, -B(OMe)2, -B(O1Pr)2, -Bpin, -Bneop, and -Beat. In some cases, each R7is selected from hydrogen, iodo, -B(OH)2, -B(OMe)2, -B(O1Pr)2, -Bpin, and -Bneop. In some cases, each R7is selected from hydrogen, iodo, -B(OH)2, -Bpin, and -Bneop. In some cases, each R7is selected from hydrogen, iodo, -Bpin, and -Bneop. In some cases, each R7is selected from hydrogen, iodo, and -Bpin. In some cases, R7is selected from hydrogen, bromo, -Bpin, and -Bneop. In some cases, R7is selected from hydrogen, bromo, and -Bpin.

[0066] In some embodiments, for a compound or salt of Formula (II), Formula (II-A),WSGR Docket No. 63230-734.601Formula (II-A*), Formula (II-B), Formula (III), Formula (III*), Formula (III-A), Formula (III-A*), Formula (IV), Formula (IV*), Formula (IV-A), Formula (IV-A*), each R5and R6are independently selected from hydrogen, -Si(R20)3, and Ci-6 alkyl; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl. In some cases, each R5and R6are independently selected from -Si(R20)3 and Ci-6 alkyl; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl. In some cases, each R5and R6are independently selected from -Si(R20)3, and Ci-6 alkyl; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-4 alkyl. In some cases, each R5and R6are independently selected from -Si(R20)3, and Ci-6 alkyl; or one R5and one R6are taken together to form a 5- to 6-membered heterocycle which is optionally substituted with one or more substituents independently selected from Ci-4 alkyl. In some cases, each R5and R6are independently selected from -Si(Me)3, -Si(Et)3, -Si(1Pr)3, -Si(nButyl)3, and Ci-6 alkyl; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-4 alkyl. In some cases, each R5and R6are independently selected from -Si(Me)3, -Si(Et)3, -Si(iPr)3, -CH3, -CH3CEE, -CH(CH3)2, -CH3CEECEE, and -C(CH3)3; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from CM alkyl. In some cases, each R5and R6are independently selected from -Si(Me)3, -Si(Et)3, -Si(1Pr)3, -CH3, and -C(CH3)3; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from CM alkyl. In some cases, each R5and R6are independently selected from -Si(Me)3, -Si(Et)3, -Si(1Pr)3, -CH3, and -C(CH3)3; or one R5and one R6are taken together to form a 5- to 6-membered heterocycle which is optionally substituted with one or more substituents independently selected from CM alkyl. In some cases, each R5and R6are independently selected from -Si(Et)3, -Si(1Pr)3, and -CH3; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from C1-4 alkyl. In some cases, each R5and R6are independently selected from -Si(1Pr)3 and -CH3; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from CM alkyl.. In some cases, each R5and R6are independently selected from -Si(1Pr)3 and -CH3; or one R5and one R6are taken together to form a 5- to 6-membered heterocycle which is optionally substituted with one or more substituents independently selected from CM alkyl. In some cases, each R5and R6are independently selected from -Si(iPr)3 and -CH3; or one R5and one R6are taken together to form aWSGR Docket No. 63230-734.601heterocycle which is optionally substituted with one or more substituents independently selected from -CH3, -CH2CH3, -CH(CH3)2, -CH2CH2CH3, and -C(CH3)3. In some cases, each R5and R6are independently selected from -Si(iPr)3 and -CH3; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from -CH3. In some cases, each R5and R6are independently selected from -Si(1Pr)3 and -CH3; or one R5and one R6are taken together to form a 5- to 6-membered heterocycle which is optionally substituted with one or more substituents independently selected from -CH3. In some cases, each R5and R6are independently selected from hydrogen, -Si(R20)3, and Ci-6 alkyl; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from CM alkyl. In some cases, each R5and R6are independently selected from hydrogen, -Si(Me)3, -Si(Et)3, -Si(1Pr)3, -Si(nButyl)3, and Ci-6 alkyl; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from CM alkyl. In some cases, each R5and R6are independently selected from hydrogen, -Si(Me)3, -Si(Et)3, -Si(1Pr)3, -Si(nButyl)3, and Ci-6 alkyl; or one R5and one R6are taken together to form a 5- to 6-membered heterocycle which is optionally substituted with one or more substituents independently selected from CM alkyl. In some cases, each R5and R6are independently selected from hydrogen, -Si(Me)3, -Si(Et)3, -Si(1Pr)3, -CH3, -CH2CH3, -CH(CH3)2, -CH2CH2CH3, and -C(CH3)3; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from C1-4 alkyl. In some cases, each R5and R6are independently selected from hydrogen, -Si(Me)3, -Si(Et)3, -Si(1Pr)3, -CH3, and -C(CH3)3; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from C1.4 alkyl. In some cases, each R5and R6are independently selected from hydrogen, -Si(Et)3, -Si(1Pr)3, and -CH3; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from CM alkyl. In some cases, each R5and R6are independently selected from hydrogen, -Si(Et)3, -Si(1Pr)3, and -CH3; or one R5and one R6are taken together to form a 5- to 6-membered heterocycle which is optionally substituted with one or more substituents independently selected from CM alkyl. In some cases, each R5and R6are independently selected from hydrogen, -Si(1Pr)3, and -CH3; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from C1-4 alkyl. In some cases, each R5and R6are independently selected from hydrogen, -Si(1Pr)3, and -CH3; or one R5and one R6are taken together to form a 5- to 6-membered heterocycle which is optionally substituted with one or more substituents independently selected from CM alkyl. In some cases, each R5and R6areWSGR Docket No. 63230-734.601independently selected from hydrogen, -Si(iPr)3, and -CH3; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from -CH3, -CH2CH3, -CH(CH3)2, -CH2CH2CH3, -C(CH3)3. In some cases, each R5and R6are independently selected from hydrogen, -Si(1Pr)3, and -CH3; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from -CH3. In some cases, each R5and R6are independently selected from hydrogen, -Si(1Pr)3, and -CH3; or one R5and one R6are taken together to form a 5- to 6-membered heterocycle which is optionally substituted with one or more substituents independently selected from -CH3.

[0067] In some embodiments, for a compound or salt of Formula (II), Formula (II- A), Formula (II-A*), Formula (II-B), Formula (III), Formula (III*), Formula (III-A), Formula (III-A*), Formula (IV), Formula (IV*), Formula (IV-A), Formula (IV-A*), each R20is independently selected from Ci-6 alkyl. In some cases, each R20is independently selected from CM alkyl. In some cases, each R20is independently selected from -CH3, -CH2CH3, -CH(CH3)2, -CH2CH2CH3, and -C(CH3)3. In some cases, each R20is independently selected from -CH3, -CH2CH3, -CH(CH3)2, and -CH2CH2CH3. In some cases, each R20is independently selected from -CH3, -CH2CH3, and -CH(CH3)2. In some cases, each R20is independently selected from -CH(CH3)2. In some cases, each R20is independently selected from -CH2CH3 and -CH(CH3)2. In some cases, each R20is independently selected from -CH3 and -CH(CH3)2. In some cases, each R20is independently selected from -CH3 and -CH2CH3.

[0068] In some embodiments, for a compound or salt of Formula (II), Formula (II-A), Formula (II-A*), Formula (II-B), Formula (III), Formula (III*), Formula (III-A), Formula (III-A*), Formula (IV), Formula (IV*), Formula (IV-A), Formula (IV-A*), each R21is independently selected from -OR22.

[0069] In some embodiments, for a compound or salt of Formula (II), Formula (II-A), Formula (II-A*), Formula (II-B), Formula (III), Formula (III*), Formula (III-A), Formula (III-A*), Formula (IV), Formula (IV*), Formula (IV-A), Formula (IV-A*), each R22is independently selected from hydrogen and Ci-6 alkyl; or two R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl. In some cases, each R22is independently selected from hydrogen and Ci-6 alkyl; or two R22on different O atoms are taken together with the O atom to which each R22is attached to form a 5- to 6-membered heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl. In some cases, each R22is independently selected from hydrogen, -CH3, -CH2CH3, and -WSGR Docket No. 63230-734.601CH(CH3)2; or two R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl. In some cases, each R22is independently selected from hydrogen, -CH3, -CH2CH3, and -CH(CH3)2; or two R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle which is optionally substituted with one or more substituents independently selected from CM alkyl. In some cases, each R22is independently selected from hydrogen, -CH3, -CH2CH3, and -CH(CH3)2; or two R22on different O atoms are taken together with the O atom to which each R22is attached to form a 5- to 6-membered heterocycle which is optionally substituted with one or more substituents independently selected from C1-4 alkyl. In some cases, each R22is independently selected from hydrogen, -CH3, and -CH(CH3)2; or two R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle which is optionally substituted with one or more substituents independently selected from C1-4 alkyl. In some cases, each R22is independently selected from hydrogen; or two R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl. In some cases, each R22is independently selected from hydrogen; or two R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle which is optionally substituted with one or more substituents independently selected from C1-4 alkyl. In some cases, each R22is independently selected from hydrogen; or two R22on different O atoms are taken together with the O atom to which each R22is attached to form a 5- to 6-membered heterocycle which is optionally substituted with one or more substituents independently selected from CM alkyl. In some cases, each R22is independently selected from hydrogen; or two R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle which is optionally substituted with one or more substituents independently selected from -CH3, -CH2CH3, and -CH(CH3)2. In some cases, two R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle, which is optionally substituted with one or more substituents independently selected from Ci-6 alkyl. In some cases, two R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle, which is optionally substituted with one or more substituents independently selected from CM alkyl. In some cases, two R22on different O atoms are taken together with the O atom to which each R22is attached to form a 5- to 6-membered heterocycle, which is optionally substituted with one or more substituents independently selected from C1.4 alkyl. In some cases, two R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle, which is optionally substituted with one or moreWSGR Docket No. 63230-734.601substituents independently selected from -CH3, -CH2CH3, and -CH(CH3)2. In some cases, two R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle, which is optionally substituted with one or more substituents independently selected from -CH3 and -CH2CH3. In some cases, two R22on different O atoms are taken together with the O atom to which each R22is attached to form a 5- to 6-membered heterocycle, which is optionally substituted with one or more substituents independently selected from -CH3 and -CH2CH3. In some cases, two R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle, which is optionally substituted with one or more substituents independently selected from -CH3. In some cases, two R22on different O atoms are taken together with the O atom to which each R22is attached to form a 5- to 6-membered heterocycle, which is optionally substituted with one or more substituents independently selected from -CH3.

[0070] In some embodiments, for a compound or salt of Formula (II), Formula (II- A), Formula (II-A*), Formula (II-B), Formula (III), Formula (III*), Formula (III-A), Formula (III-A*), Formula (IV), Formula (IV*), Formula (IV-A), Formula (IV-A*), each R23is independently selected from Ci-6 alkyl which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, -N(CI-6 alkyl)2, Ci-6 alkyl, -Ci-6 haloalkyl, and -O-Ci-6 alkyl. In some cases, each R23is independently selected from Ci-6 alkyl which is optionally substituted with one or more substituents independently selected from fluoro, chloro, -OH, -CN, Ci-6 alkyl, -Ci-6 haloalkyl, and -O-Ci-6 alkyl. In some cases, each R23is independently selected from Ci-6 alkyl which is optionally substituted with one or more substituents independently selected from fluoro, Ci-6 alkyl, -Ci-6 haloalkyl, and -O-Ci-6 alkyl. In some cases, each R23is independently selected from Ci-6 alkyl which is optionally substituted with one or more substituents independently selected from Ci-6 alkyl, -Ci-6 haloalkyl, and -O-Ci-6 alkyl. In some cases, each R23is independently selected from Ci-6 alkyl which is optionally substituted with one or more substituents independently selected from fluoro, Ci-6 alkyl, and -O-Ci-6 alkyl. In some cases, each R23is independently selected from Ci-6 alkyl. In some cases, each R23is independently selected from -CH3, -CH2CH3, -CH(CH3)2, -CH2CH2CH3, and -C(CH3)3. In some cases, each R23is independently selected from -CH3, -CH(CH3)2, and -C(CH3)3. In some cases, each R23is independently selected from -CH3 and -C(CH3)3. In some cases, each R23is independently selected from -C(CH3)3. In some cases, each R23is independently selected from -CH3.

[0071] In some embodiments, for a compound or salt of Formula (II), Formula (II-A), Formula (II-A*), Formula (II-B), Formula (III), Formula (III*), Formula (III-A), Formula (III-A*), Formula (IV), Formula (IV*), Formula (IV-A), Formula (IV-A*), each m is independentlyWSGR Docket No. 63230-734.601selected from 1 to 30. In some cases, each m is independently selected from 1 to 25. In some cases, each m is independently selected from 1 to 20. In some cases, each m is independently selected from 1 to 15. In some cases, each m is independently selected from 1 to 10. In some cases, each m is independently selected from 1 to 5. In some cases, each m is independently selected from 5 to 10. In some cases, each m is independently selected from 5 to 15. In some cases, each m is independently selected from 5 to 20. In some cases, each m is independently selected from 2 to 30. In some cases, each m is independently selected from 2 to 25. In some cases, each m is independently selected from 2 to 20. In some cases, each m is independently selected from 2 to 15. In some cases, each m is independently selected from 2 to 10. In some cases, each m is independently selected from 3 to 30. In some cases, each m is independently selected from 3 to 25. In some cases, each m is independently selected from 3 to 20. In some cases, each m is independently selected from 3 to 15. In some cases, each m is independently selected from 3 to 10. In some cases, each m is independently 0 or 1. In some cases, each m is independently 1 or 2. In some cases, each m is independently 2 or 3. In some cases, each m is independently 3 or 4. In some cases, each m is independently 4 or 5. In some cases, each m is independently 5 or 6. In some cases, each m is independently 6 or 7. In some cases, each m is independently 7 or 8. In some cases, each m is independently 8 or 9. In some cases, each m is independently 9 or 10. In some cases, each m is independently 10 or 11. In some cases, each m is independently 11 or 12. In some cases, each m is independently 12 or 13. In some cases, each m is independently 13 or 14. In some cases, each m is independently 14 or 15. In some cases, each m is independently 15 or 16. In some cases, each m is independently 16 or 17. In some cases, each m is independently 17 or 18. In some cases, each m is independently 18 or 19. In some cases, each m is independently 19 or 20. In some cases, each m is independently 20 or 21. In some cases, each m is independently 21 or 22. In some cases, each m is independently 22 or 23. In some cases, each m is independently 23 or 24. In some cases, each m is independently 24 or 25. In some cases, each m is independently less than 35. In some cases, each m is independently less than 30. In some cases, each m is independently less than 25. In some cases, each m is independently less than 20.

[0072] In some cases, for a compound or salt of Formula (II), Formula (III) Formula (III*), Formula (IV) or Formula (IV*), the compound is selected from:WSGR Docket No. 63230-734.601TIPSOWSGR Docket No. 63230-734.601TIPSOacceptable salt of any one thereof.

[0073] In some cases, for a compound or salt of Formula (II), the compound is selected from:or a pharmaceutically acceptable salt of any one thereof.WSGR Docket No. 63230-734.601

[0074] In some cases, for a compound or salt of Formula (III) or Formula (III*), the compound is selected from:or a pharmaceutically acceptable salt of any one thereof.

[0075] In some cases, for a compound or salt of Formula (IV) or Formula (IV*), the compound is selected from:WSGR Docket No. 63230-734.601, or a pharmaceutically acceptable salt of any one thereof.Certain Terminology

[0076] Unless otherwise stated, the following terms used in this application have the definitions given below. The use of the term “including” as well as other forms, such as “include”, “includes,” and “included,” is not limiting. The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

[0077] As used herein, Ci-Cxand Ci-Xare equivalent. Ci-Cxincludes C1-C2, C1-C3... Ci-Cx; and Ci-Xincludes C1-2, C1-3... Ci-X. By way of example only, a group designated as " C1-C4" indicates that there are one to four carbon atoms in the moiety, i.e. groups containing 1 carbon atom, 2 carbon atoms, 3 carbon atoms or 4 carbon atoms. Thus, by way of example only, " C1-C4 alkyl" indicates that there are one to four carbon atoms in the alkyl group, i.e., the alkyl group is selected from among methyl, ethyl, propyl, Ao-propyl, / / -butyl, Ao-butyl,.scc-butyl, and Abutyl.

[0078] An “alkyl” group refers to a saturated aliphatic hydrocarbon group. The alkyl group is branched or straight chain. In some embodiments, the “alkyl” group has 1 to 10 carbon atoms, i.e. a C1-C10alkyl. Whenever it appears herein, a numerical range such as “1 to 10” refers to eachWSGR Docket No. 63230-734.601integer in the given range; e.g., “1 to 10 carbon atoms” means that the alkyl group consist of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms, 6 carbon atoms, etc., up to and including 10 carbon atoms, although the present definition also covers the occurrence of the term “alkyl” where no numerical range is designated. In some embodiments, an alkyl is a C1-C6alkyl. In one aspect the alkyl is methyl, ethyl, propyl, iso-propyl, n-butyl, isobutyl, sec-butyl, or t-butyl. Typical alkyl groups include, but are in no way limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tertiary butyl, pentyl, neopentyl, or hexyl.

[0079] An “alkylene” group refers to a divalent alkyl radical. Any of the above-mentioned monovalent alkyl groups may be an alkylene by abstraction of a second hydrogen atom from the alkyl. In some embodiments, an alkylene is a C1-C6alkylene. In other embodiments, an alkylene is a C1-C4alkylene. In certain embodiments, an alkylene comprises one to four carbon atoms (e.g., C1-C4 alkylene). In other embodiments, an alkylene comprises one to three carbon atoms (e.g., C1-C3 alkylene). In other embodiments, an alkylene comprises one to two carbon atoms (e.g., Ci-C2 alkylene). In other embodiments, an alkylene comprises one carbon atom (e.g., Ci alkylene). In other embodiments, an alkylene comprises two carbon atoms (e.g., C2 alkylene). In other embodiments, an alkylene comprises two to four carbon atoms (e.g., C2-C4 alkylene). Typical alkylene groups include, but are not limited to, -CH2-, -CH(CH3)-, -C(CH3)2-, -CH2CH2-, -CH2CH(CH3)-, -CH2C(CH3)2-, -CH2CH2CH2-, -CH2CH2CH2CH2-, and the like.

[0080] “Deuteroalkyl” refers to an alkyl group where 1 or more hydrogen atoms of an alkyl are replaced with deuterium.

[0081] The term “alkenyl” refers to a type of alkyl group in which at least one carbon-carbon double bond is present. In one embodiment, an alkenyl group has the formula -C(R)=CR.2, wherein R refers to the remaining portions of the alkenyl group, which may be the same or different. In some embodiments, R is H or an alkyl. In some embodiments, an alkenyl is selected from ethenyl i.e., vinyl), propenyl i.e., allyl), butenyl, pentenyl, pentadienyl, and the like. Nonlimiting examples of an alkenyl group include -CH=CH2, -C(CH3)=CH2, -CH=CHCH3, -C(CH3)=CHCH3, and -CH2CH=CH2.

[0082] The term “alkynyl” refers to a type of alkyl group in which at least one carbon-carbon triple bond is present. In one embodiment, an alkenyl group has the formula -C=C-R, wherein R refers to the remaining portions of the alkynyl group. In some embodiments, R is H or an alkyl. In some embodiments, an alkynyl is selected from ethynyl, propynyl, butynyl, pentynyl, hexynyl, and the like. Non-limiting examples of an alkynyl group include -C=CH, -C≡CCH3-C≡CCH2CH3, -CH2C=CH.

[0083] An “alkoxy” group refers to a (alkyl)O- group, where alkyl is as defined herein.WSGR Docket No. 63230-734.601

[0084] The term “alkylamine” refers to the -N(alkyl)xHygroup, where x is 0 and y is 2, or where x is 1 and y is 1, or where x is 2 and y is 0.

[0085] The term “aromatic” refers to a planar ring having a delocalized π-electron system containing 4n+2 π electrons, where n is an integer. The term “aromatic” includes both carbocyclic aryl (“aryl”, e.g., phenyl) and heterocyclic aryl (or “heteroaryl” or “heteroaromatic”) groups (e.g., pyridine). The term includes monocyclic or fused-ring polycyclic (z.e., rings which share adjacent pairs of carbon atoms) groups.

[0086] The term “carbocyclic” or “carbocycle” refers to a ring or ring system where the atoms forming the backbone of the ring are all carbon atoms. The term thus distinguishes carbocyclic from “heterocyclic” rings or “heterocycles” in which the ring backbone contains at least one atom that is different from carbon. In some embodiments, carbocycles are monocyclic, bicyclic, multicyclic, spirocyclic or bridged rings. In some embodiments, a carbocycle is a monocyclic carbocycle or a bicyclic carbocycle. In some embodiments, at least one of the two rings of a bicyclic carbocycle is aromatic. In some embodiments, one of the two rings of a bicyclic carbocycle is aromatic, and the point of attachment to the remaining of the compound is at a carbon atom of the aromatic ring. In some embodiments, one of the two rings of a bicyclic carbocycle is aromatic, and the point of attachment to the remaining of the compound is at a carbon atom of the non-aromatic ring. In some embodiments, bicyclic carbocycle is a fused bicyclic carbocycle. In some embodiments, both rings of a fused bicyclic carbocycle are aromatic (i.e., an aryl). Carbocycle includes cycloalkyl and aryl.

[0087] The term “bicyclic carbocyclic” refers to two carbocycles that are fused together and share two adjacent carbon atoms.

[0088] As used herein, the term “aryl” refers to an aromatic ring wherein each of the atoms forming the ring is a carbon atom. In one aspect, aryl is phenyl, naphthyl, or biphenyl. In some embodiments, an aryl is a phenyl. In some embodiments, aryl is biphenyl. In some embodiments, an aryl is a C6-C12aryl. In some embodiments, an aryl is a C6-C10aryl. Depending on the structure, an aryl group is a monoradical or a diradical (i.e., an arylene group).

[0089] The term “cycloalkyl” refers to a stable, partially or fully saturated, monocyclic or polycyclic carbocyclic ring, which may include fused (when fused with an aryl or a heteroaryl ring, the cycloalkyl is bonded through a non-aromatic ring atom) or bridged ring systems.Representative cycloalkyls include, but are not limited to, cycloalkyls having from three to fifteen carbon atoms (C3-C15 cycloalkyl), from three to ten carbon atoms (C3-C10 cycloalkyl), from three to eight carbon atoms (C3-C8 cycloalkyl), from three to six carbon atoms (C3-C6 cycloalkyl), from three to five carbon atoms (C3-C5 cycloalkyl), or three to four carbon atoms (C3-C4 cycloalkyl). InWSGR Docket No. 63230-734.601some embodiments, the cycloalkyl is a 3- to 6-membered cycloalkyl. In some embodiments, the cycloalkyl is a 5- to 6-membered cycloalkyl.

[0090] The term “monocyclic cycloalkyl” refers to cyclic saturated aliphatic hydrocarbon that has one ring. Monocyclic cycloalkyls include from 3 to 10 carbon atoms in the ring (i.e., a monocyclic C3-C10cycloalkyl). Monocyclic cycloalkyls that include 3 to 10 carbon atoms in the ring include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononane, and cyclodecane. In some embodiments, a monocyclic cycloalkyl is a monocyclic C3-C6cycloalkyl. Monocyclic C3-C6cycloalkyls include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0091] The term “cycloalkenyl” refers to a type of non-aromatic cycloalkyl group in which at least one carbon-carbon double bond is present. In some embodiments, cycloalkenyl is a monocyclic cycloalkenyl.

[0092] In some embodiments, monocyclic cycloalkenyl has 5 to 12 carbon atoms (i.e., a C5-C12cycloalkenyl). In some embodiments, monocyclic cycloalkenyl has 5 to 8 carbon atoms (i.e., a C5-C12cycloalkenyl). Non-limiting examples of cycloalkenyls include:0000.0

[0093] The term “halo” or, alternatively, “halogen” or “halide” means fluoro, chloro, bromo, or iodo. In some embodiments, halo is F, Cl, Br, or I. In some embodiments, halo is fluoro, chloro, or bromo. In some embodiments, halo is F, Cl, or Br.

[0094] The term “haloalkyl” refers to an alkyl in which one or more hydrogen atoms are replaced by a halogen atom. In one aspect, a haloalkyl is a Ci-Cefluoroalkyl, Ci-Cechloroalkyl, or Ci-Cebromoalkyl. In some cases, a haloalkyl is a Ci-Cefluoroalkyl.

[0095] The term “fluoroalkyl” refers to an alkyl in which one or more hydrogen atoms are replaced by a fluorine atom. In one aspect, a fluoroalkyl is a Ci-Cefluoroalkyl. In some embodiments, a fluoroalkyl is selected from trifluoromethyl, difluoromethyl, fluoromethyl, 2,2,2-trifluoroethyl, 1 -fluoromethyl -2 -fluoroethyl, and the like. In some cases, a fluoroalkyl is selected from trifluoromethyl, difluoromethyl, and fluoromethyl.

[0096] The term “heteroalkyl” refers to an alkyl group in which one or more skeletal atoms of the alkyl are selected from an atom other than carbon, e.g., oxygen, nitrogen (e.g. -NH-, -N(alkyl)-, sulfur, or combinations thereof. A heteroalkyl is attached to the rest of the molecule at a carbon atom of the heteroalkyl. In one aspect, a heteroalkyl is a Ci-Ceheteroalkyl. In some cases, a Ci-Ceheteroalkyl isWSGR Docket No. 63230-734.601

[0097] The term “heterocycle” or “heterocyclic” refers to heteroaromatic rings (also known as heteroaryls) and heterocycloalkyl rings containing one to four heteroatoms in the ring(s), where each heteroatom in the ring(s) is selected from O, S and N, wherein each heterocyclic group has from 3 to 10 atoms in its ring system, and with the proviso that any ring does not contain two adjacent O or S atoms. Non-aromatic heterocyclic groups (also known as heterocycloalkyls) include rings having 3 to 10 atoms in its ring system and aromatic heterocyclic groups include rings having 5 to 10 atoms in its ring system. The heterocyclic groups include benzo-fused ring systems. Examples of non-aromatic heterocyclic groups are pyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothienyl, oxazolidinonyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothiopyranyl, piperidinyl, morpholinyl, thiomorpholinyl, thioxanyl, piperazinyl, aziridinyl, azetidinyl, oxetanyl, thietanyl, homopiperidinyl, oxepanyl, thiepanyl, oxazepinyl, diazepinyl, thiazepinyl, 1,2,3,6-tetrahydropyridinyl, pyrrolin-2-yl, pyrrolin-3-yl, indolinyl, 2H-pyranyl, 4H-pyranyl, dioxanyl, 1,3-dioxolanyl, pyrazolinyl, dithianyl, dithiolanyl, dihydropyranyl, dihydrothienyl, dihydrofuranyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, 3-azabicyclo[3.1.0]hexanyl, 3-azabicyclo[4.1.0]heptanyl, 3H-indolyl, indolin-2-onyl, isoindolin-1-onyl, isoindoline- 1,3 -di onyl, 3,4-dihydroisoquinolin-l(2H)-onyl, 3,4-dihydroquinolin-2(lH)-onyl, isoindoline- 1, 3 -dithionyl, benzo[d]oxazol-2(3H)-onyl, lH-benzo[d]imidazol-2(3H)-onyl, benzo[d]thiazol-2(3H)-onyl, and quinolizinyl. Examples of aromatic heterocyclic groups are pyridinyl, imidazolyl, pyrimidinyl, pyrazolyl, triazolyl, pyrazinyl, tetrazolyl, furyl, thienyl, isoxazolyl, thiazolyl, oxazolyl, isothiazolyl, pyrrolyl, quinolinyl, isoquinolinyl, indolyl, benzimidazolyl, benzofuranyl, cinnolinyl, indazolyl, indolizinyl, phthalazinyl, pyridazinyl, triazinyl, isoindolyl, pteridinyl, purinyl, oxadiazolyl, thiadiazolyl, furazanyl, benzofurazanyl, benzothiophenyl, benzothiazolyl, benzoxazolyl, quinazolinyl, quinoxalinyl, naphthyridinyl, and furopyridinyl. The foregoing groups are either C-attached (or C-linked) or TV-attached where such is possible. For instance, a group derived from pyrrole includes both pyrrol-l-yl (TV-attached) or pyrrol-3-yl (C-attached). Further, a group derived from imidazole includes imidazol-l-yl or imidazol-3-yl (both TV-attached) or imidazol-2-yl, imidazol-4-yl or imidazol-5-yl (all C-attached). The heterocyclic groups include benzo-fused ring systems. Non-aromatic heterocycles are optionally substituted with one or two oxo (=0) moieties, such as pyrrolidin-2-one. In some embodiments, at least one of the two rings of a bicyclic heterocycle is aromatic. In some embodiments, both rings of a bicyclic heterocycle are aromatic.

[0098] The terms “heteroaryl” or, alternatively, “heteroaromatic” refers to an aryl group thatWSGR Docket No. 63230-734.601includes one or more ring heteroatoms selected from nitrogen, oxygen, and sulfur. Illustrative examples of heteroaryl groups include monocyclic heteroaryls and bicyclic heteroaryls.Monocyclic heteroaryls include pyridinyl, imidazolyl, pyrimidinyl, pyrazolyl, triazolyl, pyrazinyl, tetrazolyl, furyl, thienyl, isoxazolyl, thiazolyl, oxazolyl, isothiazolyl, pyrrolyl, pyridazinyl, triazinyl, oxadiazolyl, thiadiazolyl, and furazanyl. Monocyclic heteroaryls include indolizine, indole, benzofuran, benzothiophene, indazole, benzimidazole, purine, quinolizine, quinoline, isoquinoline, cinnoline, phthalazine, quinazoline, quinoxaline, 1,8-naphthyridine, and pteridine. In some embodiments, a heteroaryl contains 0-4 N atoms in the ring. In some embodiments, a heteroaryl contains 1-4 N atoms in the ring. In some embodiments, a heteroaryl contains 0-4 N atoms, 0-1 0 atoms, and 0-1 S atoms in the ring. In some embodiments, a heteroaryl contains 1-4 N atoms, 0-1 O atoms, and 0-1 S atoms in the ring. In some embodiments, heteroaryl is a C1-C9heteroaryl. In some embodiments, monocyclic heteroaryl is a C1-C5heteroaryl. In some embodiments, monocyclic heteroaryl is a 5-membered or 6-membered heteroaryl. In some embodiments, bicyclic heteroaryl is a C6-C9heteroaryl.

[0099] A “heterocycloalkyl” group refers to a cycloalkyl group that includes at least one heteroatom selected from nitrogen, oxygen and sulfur. In some embodiments, a heterocycloalkyl is fused with an aryl or heteroaryl. In some embodiments, the heterocycloalkyl is oxazolidinonyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, tetrahydropyranyl, tetrahydrothiopyranyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl, piperidin-2-onyl, pyrrolidine-2, 5-dithionyl, pyrrolidine-2, 5-dionyl, pyrrolidinonyl, imidazolidinyl, imidazolidin-2-onyl, or thiazolidin-2-onyl. In one aspect, a heterocycloalkyl is a C2-Cioheterocycloalkyl. In another aspect, a heterocycloalkyl is a C4-Cioheterocycloalkyl. In some embodiments, a heterocycloalkyl is monocyclic or bicyclic. In some embodiments, a heterocycloalkyl is monocyclic and is a 3, 4, 5, 6, 7, or 8-membered ring. In some embodiments, a heterocycloalkyl is monocyclic and is a 3, 4, 5, or 6-membered ring. In some embodiments, a heterocycloalkyl is monocyclic and is a 3 or 4-membered ring. In some embodiments, a heterocycloalkyl contains 0-2 N atoms in the ring. In some embodiments, a heterocycloalkyl contains 0-2 N atoms, 0-2 O atoms and 0-1 S atoms in the ring.

[0100] The term “bond” or “single bond” refers to a chemical bond between two atoms, or two moieties when the atoms joined by the bond are considered to be part of larger substructure. In one aspect, when a group described herein is a bond, the referenced group is absent thereby allowing a bond to be formed between the remaining identified groups.

[0101] The term “moiety” refers to a specific segment or functional group of a molecule. Chemical moieties are often recognized chemical entities embedded in or appended to a molecule.

[0102] The term “oligomer” refers to a compound consisting of repeating subunits. In someWSGR Docket No. 63230-734.601embodiments, the repeating subunits are of the same molecular structure. In some cases, the repeating subunits have different molecular structure. By way of example only, an oligomer is acompound represented by the structure selected from:, wherein, and represent different subunits; each n is independently selectedeB C from 1 to 20; and the wiggle lin * denotes a point of attachment to another subunitDor. Depending on the structure of the subunit, the subunit is a monoradical(diradical ( | ’_r ' —-i_ ' | ‘ ), a triradical ( H ), or a tetraradical ( H — UH. In some cases, oligomer comprise a linear structure. In some cases, an oligomer comprises a branched structure.

[0103] The term “optionally substituted” or “substituted” means that the referenced group is optionally substituted with one or more additional group(s) individually and independently selected from D, halogen, -CN, -NEb, -NH(alkyl), -N(alkyl)2, -OH, -CO2H, -CO2alkyl, - C(=O)NH2, -C(=O)NH(alkyl), -C(=O)N(alkyl)2, -S(=O)2NH2, -S(=O)2NH(alkyl), -S(=O)2N(alkyl)2, alkyl, cycloalkyl, fluoroalkyl, heteroalkyl, alkoxy, fluoroalkoxy, heterocycloalkyl, aryl, heteroaryl, aryloxy, alkylthio, arylthio, alkylsulfoxide, arylsulfoxide, alkylsulfone, and arylsulfone. In some other embodiments, optional substituents are independently selected from D, halogen, -CN, -NH2, -NH(CH3), -N(CH3)2, -OH, -CO2H, -CO2(Ci-C4alkyl), -C(=O)NH2, -C(=O)NH(Ci-C4alkyl), -C(=O)N(Ci-C4alkyl)2, -S(=O)2NH2, -S(=O)2NH(Ci-C4alkyl), -S(=O)2N(Ci-C4alkyl)2, Ci-C4alkyl, C3-C6cycloalkyl, Ci-C4fluoroalkyl, Ci-C4heteroalkyl, Ci-C4alkoxy, Ci-C4fluoroalkoxy, -SCi-C4alkyl, -S(=O)Ci-C4alkyl, and -S(=O)2Ci-C4alkyl. In some embodiments, optional substituents are independently selected from D, halogen, -CN, -NH2, -OH, -NH(CH3), -N(CH3)2, -CH3, -CH2CH3, -CF3, -OCH3, and -OCF3. In some embodiments, substituted groups are substituted with one or two of the preceding groups. In some embodiments, an optional substituent on an aliphatic carbon atom (acyclic or cyclic) includes oxo (=0).EXAMPLES

[0104] The disclosure now being generally described, it will be more readily understood byWSGR Docket No. 63230-734.601reference to the following examples which are included merely for purposes of illustration of certain aspects and embodiments of the present disclosure and are not intended to limit the disclosure in any way.Materials and methods

[0105] Commercial reagents were purchased from standard commercial suppliers such as Sigma Aldrich, Alfa Aesar, Strem Chemicals, TCI, or Oakwood Chemicals, and used as received unless otherwise indicated.

[0106] THF was dried and purified using a PureSolv MD 7 (from Innovative Technology) or MB SPS 800 (from MBraun). Cyclohexane and quinoline were distilled over CaH2 under N2. [Ir(COD)(OMe)]2 was purchased from Sigma Aldrich and stored inside of a MBraun Labmaster glove box (<1 ppm O2 and H2O) filled with a dry N2 atmosphere at -20 °C. Unless otherwise noted, reactions were performed in flame-dried glassware under a positive pressure of N2 using standard synthetic organic, inert atmosphere techniques. Organic solutions were concentrated under reduced pressure on a rotary evaporator.

[0107] Proton nuclear magnetic resonance (1H NMR) spectra were acquired using Varian Mercury 400 MHz, Varian Inova QANUC 500 MHz, Varian VNMRS 500 MHz, Bruker AVIIIHD 500 MHz, or Bruker AVIIIHD 400 MHz spectrometers. Carbon nuclear magnetic resonance (13C NMR) spectra were acquired using Varian VNMRS 125 MHz, Bruker AVIIIHD 125 MHz, or Bruker AVIIIHD 101 MHz spectrometers. Chemical shifts (5) are reported in parts per million (ppm) and 'H and13C are internally referenced to the residual solvent signals (CDCh: 7.26 ppm (' H) and 77.16 ppm (13C), de-acetone: 2.05 ppm ( 'H) and 206.26 ppm (13C), CD2Cl2: 5.32 ppm (' H) and 53.84 ppm (13C), and de-DMSO: 2.50 ppm (' H) and 39.52 ppm (13C).19F NMR spectra were recorded on a Bruker NanoBay Avance III HD NMR 400 MHz and are reported unreferenced. The multiplicity is denoted as follows: s = singlet, brs = broad singlet, d = doublet, t = triplet, q = quartet, p = pentet, h = hextet, hept = heptet, m = multiplet, br = broad.

[0108] High resolution mass spectra (HRMS) were recorded using a Bruker maXis Impact TOF mass spectrometer. Fourier-transform infrared (FT-IR) spectra were recorded on an alpha Bruker FT-IR spectrometer.

[0109] Analytical thin-layer chromatography was performed on pre-coated 250 mm layer thickness silica gel 60 F254 plates (EMD Chemicals Inc.). Visualization was performed by ultraviolet light and / or by staining with potassium permanganate or cerium molybdate.Purifications by column chromatography were performed using either a Biotage Isolera™ One or standard column chromatography using silica gel (40-63 pm, 230-400 mesh).

[0110] The following abbreviations and terms have the indicated meanings throughout:WSGR Docket No. 63230-734.601Aq or aq = aqueous; MeOH = methanol; EtOH = ethanol; IPA = isopropyl alcohol EtOAc or EA = ethyl acetate; MeCN or ACN = acetonitrileDCM or CH2Q2 = di chloromethane or methylene chloride; DCE = 1,2-di chloroethane Et2O = diethyl ether; MTBE = methyl tert-butyl ether; CPME = cyclopropyl methyl ether THF = tetrahydrofuran; Me-THF or Methyl THF = 2-methyltetrahydrofuranDMSO = dimethylsulfoxide; DMF = N, N-dimethylformamideAcOH or MeCO2H = acetic acid; HCO2H = formic acidTFA = tri fluoroacetic acid; TFAA = trifluoroacetic anhydridePBS = phosphate buffered salineNaBH(0Ac)3 = sodium triacetoxyborohydrideNaOEt = sodium ethoxide; NaOAc = sodium acetate; Na2CO3 = sodium carbonateEt3N = triethylamine; DMAP = 4-dimethylaminopyridine; NMM = N-methylmorpholine DBU = l,8-diazabicyclo[5.4.0]undec-7-eneTMSOTf = trimethyl silyl trifluoromethanesulfonatemCPBA = meto-chloroperoxybenzoic acid; TEMPO = (2,2,6,6-Tetramethylpiperidin-l-yl)oxyl BOC2O = di- / c / 7-butyl decarbonate; Boc = tert-butyl carboxylEDC = N-Ethyl-N'-(3-dimethylaminopropyl)carbodiimide hydrochlorideDIC = N, N'-DiisopropylcarbodiimideTMS = trimethyl silylN2 = nitrogen gas; H2 = hydrogen gasAc= acetyl; Cbz = carbobenzyl oxy; Phth = phthalimidyl;Me = methyl; Et = ethyl; 'Bu or / Bu = tert-butyl; Ph = phenyl; Bn = benzyl; Bz = benzoyl Nuc = nucleophilert or RT = room temperatureeq. or equiv. = equivalent s)cv = column volumenm = nanometermg = milligram; g= gram; kg or Kg = kilogramca.= about or approximatelymin = minute; h or hr = hour; hrs = hourspL = microliter; mL = milliliter; L = litermmol = millimole; M = molarA= angstromm / z = mass-to-charge ratioWSGR Docket No. 63230-734.601TLC = thin-layer chromatography; LC / MS or LCMS = liquid chromatography -mass spectrometryHPLC = high pressure liquid chromatography; HRMS = high resolution mass spectrometry FTIR or IR = Fourier transform infraredNMR = nuclear magnetic resonanceTOF = time-of-flightExample A-l: Synthesis of C2-C-7 bidirectional extension unit (6a)1a 4a 5a 6a

[0111] Step 1: Synthesis of tert-butyl 2,2-dimethyl-5H-[l,3]dioxolo[4,5-f]indole-5-carboxylate (2a)1a 2a

[0112] A 500 mL flame-dried, round-bottom flask, equipped with a Teflon-coated stir bar and rubber septum, was charged with 2,2-dimethyl-5H-[l,3]dioxolo[4,5-f]indole (la) (9.5 g, 50.0 mmol, 1 equiv), DMAP (610.9 mg, 5.0 mmol, 0.1 equiv) andBoc2O (12.0 g, 55.0 mmol, 1.1 equiv) followed by THF (250 mL, 0.20 M). The resulting homogeneous reaction mixture was then stirred at ambient temperature for 12 h before concentrated in vacuo. The resulting crude reaction mixture was purified by column chromatography (5% EtOAc in hexanes) to afford compound 2a as white solid (13.02 g, 45.0 mmol) in 90% yield.

[0113] 'H NMR (400 MHz, CDCh) 87.57 (brs, 1H), 7.44 (d, = 3.7 Hz, 1H), 6.83 (s, 1H), 6.42 (dd, = 3.7, 0.7 Hz, 1H), 1.69 (s, 6H), 1.67 (s, 9H). 13C NMR (126 MHz, CDCl3) δ 149.92, 146.20, 144.51, 129.87, 124.32, 117.87, 107.47, 99.57, 96.85, 83.64, 28.34, 25.91. HRMS: Calcd. For C16H19O4NNa [M+Na]+=312.12063 m / z, found =312.12031 m / z. R / = (EtOAc / hexanes, 1:9) 0.65. IR (neat) v = 3154, 3120, 2982, 2935, 1729, 1471, 1392, 1292, 1137, 998, 867, 835, 769, 752 cm'1.

[0114] Step-2: Synthesis of tert-butyl 2,2-dimethyl-6-(trimethylsilyl)-5H-[l,3]dioxolo[4,5-f]indole-5-carboxylate (3a)WSGR Docket No. 63230-734.601TMSCI (1.5 equiv) LDA (1.5 equiv) THF (0.2 M) -78 °C, 20 min3a

[0115] A 500 mL flame-dried, round-botom flask, equipped with a Teflon-coated stir bar and rubber septum, was charged with compound 2a (10.7 g, 37.0 mmol, 1 equiv). The flask was then evacuated and backfilled with N2 for three times before addition of dry, degassed THF (185 mL, 0.2 M). To the resulting homogeneous reaction solution was added TMSCI (7.0 mL, 55.5 mmol, 1.5 equiv), and LDA (27.8 mL, 55.5 mmol, 1.5 equiv, 2.0 M in THF) dropwise at -78 °C in a dry ice / acetone dewer bath under a N2 atmosphere. The reaction mixture was stirred at -78 °C for 20 min prior to quenching by saturated aqueous NH4CI solution. The resulting mixture was then extracted three times with EtOAc (50 mL x 3). The combined organic fractions were washed with brine, dried over MgSCU, filtered, and concentrated in vacuo. The resulting residue was purified using silica gel column chromatography (5% EtOAc in hexanes) to afford compound 3a as a white solid (12.5 g, 34.8 mmol) in 94% yield.

[0116] 1HNMR(500MHz, CDCh) 87.41 (s, 1H), 6.80 (s, 1H), 6.68 (s, 1H), 1.69 (s, 6H), 1.69 (s, 9H), 0.31 (s, 9H).13C NMR (126 MHz, CDCh) 6 151.15, 146.47, 144.33, 140.46, 132.53, 124.85, 119.38, 117.94, 99.07, 97.09, 83.90, 28.36, 25.90, 0.21.; HRMS: Calcd. for C19H27O4NNaSi [M+Na]+=384.16016 m / z, found =384.15958 m / z. R / = (EtOAc / hexanes, 1:9) 0.69; IR (neat) v = 2979, 2903, 1726, 1472, 1382, 1326, 1203, 1159,1150, 1129, 1027, 904, 842, 768, 632 cm'1.

[0117] Step-3: Synthesis of 2,2-dimethyl-6-(trimethylsilyl)-5H-[l,3]dioxolo[4,5-f]indole (4a)3a 4a

[0118] A flame-dried, 250 mL round-botom flask equipped with a Teflon-coated stir bar and rubber septum was charged with compound 3a (3.9 g, 10.0 mmol, 1 equiv) and DMF (36 mL, 0.3 M). The resulting homogenous solution was heated at reflux (135 °C) under N2 and allowed toWSGR Docket No. 63230-734.601cool to ambient temperature after 5 h. The resulting mixture was then extracted three times with EtOAc (50 mL x 3). The combined organic fractions were washed with H2O and brine, dried over MgSCU, filtered, and concentrated in vacuo. The resulting residue was recrystallized with toluene (13 mL) at 65 °C then cooled down to -20 °C. Filtration afforded compound 4a as a white crystal (2.4 g, 9.2 mmol) in 84% yield.

[0119] 'H NMR (500 MHz, CDCh) 87.93 (brs, 1H), 6.88 (t, J= 0.7 Hz, 1H), 6.76 (t, J= 0.7 Hz, 1H), 6.58 (dd, J= 2.2, 1.0 Hz, 1H), 1.68 (s, 6H), 0.31 (s, 9H).13C NMR (126 MHz, CDCh) 6 145.65, 143.40, 136.29, 133.75, 122.33, 117.22, 111.55, 98.56, 91.40, 25.86, -0.84.; HRMS: Calcd. for C14H19NNaO2Si [M+Na]+ = 284.1077 m / z, found = 284.1081 m / z. R / = (hexanes / EtO Ac, 9:1) 0.53. IR (neat) v = 3409, 2985, 2957, 1504, 1451, 1384, 1230, 1153, 1103, 982, 948, 872, 835, 780, 752, 659, 627 cm'1.

[0120] Step 4: Synthesis of 2,2-dimethyl-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-6-(trimethylsilyl)-5H- [1,3] dioxolo [4,5-f] indole (5)

[0121] The reaction was carried out according to the General Procedure 2 and was performed in cyclohexanes at room temperature for 40 min. Reagents: compound 4a (2.6 g, 10 mmol, 1.0 equiv), [Ir(OMe)(COD)]2 (99.43 mg, 0.15 mmol, 1.5 mol%), dtbpy (80.52 mg, 0.30 mmol, 3.0 mol%), B2pin2(2.5 g, 10 mmol, 1.0 equiv), and Cyclohexanes (25 mL, 0.4M).Purification: 10% EtOAc in hexanes. Compound 5, 83% (3.2 g, 8.3 mmol), light yellow solid.

[0122] 'H NMR (500 MHz, CDCh) 69.24 (brs, 1H), 6.98 (s, 1H), 6.56 (d, J= 2.3 Hz, 1H), 1.70 (s, 6H), 1.40 (s, 12H), 0.32 (s, 9H).13C NMR (126 MHz, CDCh) 6 151.78, 142.87, 138.35, 135.34, 121.11, 117.30, 110.54, 102.04, 83.71, 26.00, 25.13, -0.88.; HRMS: Calcd. for C20H31O4NBSi [M+H]+=388.21099 m / z, found =388.21015 m / z. R / = (EtOAc / hexanes, 1:9) 0.50. IR (neat) v = 3441, 2982, 2954, 1613, 1452, 1385, 1289, 1194, 1137, 1104, 1061, 991, 836, 754, 667, 628 cm'1.

[0123] Step 5: Synthesis of 4-iodo-2,2-dimethyl-6-(trimethylsilyl)-5H-[l,3]dioxolo[4,5-f] indole (6a)WSGR Docket No. 63230-734.601

[0124] A 50 mL round-bottom flask equipped with a Teflon-coated stir bar and rubber septum was charged with (2,2-dimethyl-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-6-(trimethylsilyl)-5H-[l,3]dioxolo[4,5-f]indole) 5 (774.72 mg, 2 mmol, 1 equiv), Cui (38.09 mg, 0.2 mmol, 10 mol%), phenanthroline (72.08 mg, 0.4 mmol, 20 mol%), KI (498.0 mg, 3 mmol, 1.5 equiv), and MeOH / H₂O (36 mL / 4 mL, 0.05 M, 9:1). The rubber septum was then connected to a tank of O2, pressurized to 50 kpa, and was vented 3 times for 10 s each time. Under a constant pressure of O2 (50 kpa), the reaction mixture was then stirred at 50 °C for 35 min before depressurizing by opening to the atmosphere and concentrated in vacuo to afford a wine-red residue. The resulting mixture was then extracted three times with EtOAc (50 mL x 3). The phases were separated, and the organic factions were washed with brine, dried over MgSCU, filtered, and concentrated in vacuo. The resulting residue was purified using silica gel column chromatography (5% EtOAc in hexanes) to afford compound 6a as a white solid (549.9 mg, 1.42 mmol) in 71% yield.

[0125] 'H NMR (500 MHz, CDCh) 87.90 (brs, 1H), 6.82 (d, J= 0.7 Hz, 1H), 6.73 (d, J= 2.3 Hz, 1H), 1.73 (s, 6H), 0.34 (s, 9H). °C NMR (126 MHz, cdch) 6 147.09, 142.52, 136.65, 135.27, 121.90, 117.82, 113.06, 98.76, 53.86, 25.97, -0.87. HRMS: Calcd. for Ci4Hi9O2NISi [M+H]+= 388.02242 m / z, found = 388.02305 m / z. R / = (EtOAc / hexanes, 1:9) 0.64; IR (neat) v = 3367, 2954, 1460, 1310, 1247, 1210, 1190, 1153, 1103, 985, 945, 923, 836, 731 cm'1.Example B: Iterative chain growth (ICG)

[0126] Scheme 2:WSGR Docket No. 63230-734.601iterative chain growth (ICG):G!Ss Bistetseftcie miy a saitebfe wyl mW;R* is G* is aKfepeBSea^ a sisiSaaie sslyi moiety: aed G2is irtsfepefttte fitly a sustabte siiyi nwietyG’ is i;i£i«p&i-sLierstt>; a suitabts: toryl moiety m is sefected IRISTI * i» 29 Example B-l: Suzuki-Miyaura Cross-Coupling of IndolesPd catalyst (5 mol%) ligand (5.5 mol%) base (2.1 equiv) solvent:H20

[0127] General Procedure 1: A flame-dried Schlenk tube equipped with a Teflon-coated stir bar and a glass stopper was charged with iodoindole (1.0 equiv), indole boronic acid pinacol ester (Bpin) (1.0-1.2 equiv), Pd-catalyst (5 mol%), ligand (5.5 mol%) and base (2.1 equiv). The Schlenk tube was evacuated and backfilled with N2 (this process was repeated three times) prior to the addition of degassed dry solvent under a positive N2 pressure, followed by addition of degassed distilled H2O. The tube was sealed and heated to the indicated temperature in a pre-heated oil bath. After the indicated time, the reaction was cooled to ambient temperature atmosphere and quenched by the addition of saturated aqueous NH4CI solution to pH=7. The phases were then separated, and the aqueous phase was extracted with EtOAc (3 x 20 mL). The combined organic fractions were then washed with brine then dried over MgSCU, filtered, and concentrated in vacuo. The resulting residue was purified by flash chromatography on silica gel using the indicated solvent system as eluent to afford the desired product.WSGR Docket No. 63230-734.601

[0128] Compounds 1 to 4 were synthesized according to General Procedure 1 with appropriate reagents and intermediates.

[0129] Compound 1, 82% (428.38 mg, 0.74 mmol), light yellow solid. The reaction was carried out according to the General Procedure 1, the reaction was performed in THF / H2O at ambient temperature for 1 h. Reagents: 6-methoxy-2-(4,4,5,5-tetram ethyl- 1,3,2-dioxaborolan-2-yl)-5-((triisopropylsilyl)oxy)- IH-indole(446.10 mg, 1.0 mmol, 1.1 equiv), compound 6a (348.56 mg, 0.9 mmol, 1.0 equiv), Pd(OAc)2 (10.10 mg, 0.045 mmol, 5 mol%), SPhos (22.58 mg, 0.049 mmol, 5.5 mol%), K3PO4(401.19 mg, 1.89 mmol, 2.1 equiv), and THF (4.0 mL), H2O (1.0 mL). Purification: 5% to 10% EtOAc in hexanes.

[0130] 1HNMR(500MHz, CDCh) 89.03 (brs, 1H), 8.51 (s, 1H), 7.17 (s, 1H), 6.96 (s, 1H), 6.89 (s, 1H), 6.71 (dd, J= 2.2, 0.8 Hz, 1H), 6.66 (d, J= 2.1 Hz, 1H), 3.89 (s, 3H), 1.78 (s, 6H), 1.40- 1.27 (m, 3H), 1.15 (d, = 7.4 Hz, 18H), 0.38 (s, 9H); 13CNMR (101 MHz, CDCH) 5 149.50, 143.21, 141.50, 141.10, 137.02, 131.10, 130.69, 130.64, 123.20, 121.76, 118.04, 112.18, 110.13, 99.74, 99.67, 98.03, 94.51, 55.97, 26.16, 18.19, 13.03, -0.76. HRMS: Calcd. for C32H46N2O4Si2 [M+H]+= 579.3069 m / z, found = 579.3064 m / z. R / = (EtOAc / hexane, 1:9): 0.46. IR (neat) v = 3450, 2950, 2870, 1480, 1300, 1160, 835, 677, 440 cm'1.WSGR Docket No. 63230-734.601

[0131] Compound 2, 86% (509.5 mg, 0.66 mmol), light yellow solid. The reaction was carried out according to the General Procedure 1, the reaction was performed in THF / H2O at ambient temperature for 1 h. Reagents: compound 6 (537.78 mg, 0.85 mmol, 1.1 equiv), compound 6a (298.21 mg, 0.77 mmol, 1.0 equiv), Pd(OAc)2(8.53 mg, 0.038 mmol, 5 mol%), SPhos (17.24 mg, 0.042 mmol, 5.5 mol%), K3PO4 (343.88 mg, 1.62 mmol, 2.1 equiv), THF (15.0 mL), and H2O (3.7 mL). Purification: 5% to 10% EtOAc in hexanes.

[0132] 'H NMR (400 MHz, CDCh) 8 10.00 (s, 1H), 9.06 (s, 1H), 8.48 (s, 1H), 7.12 (s, 1H), 7.00 (s, 1H), 6.98 (s, 1H), 6.92 (s, 1H), 6.85 (d, J= 2.1 Hz, 1H), 6.78 (d, J= 2.3 Hz, 1H), 6.69 (d, J=2.1 Hz, 1H), 3.90 (s, 3H), 1.85 (s, 6H), 1.83 (s, 6H), 1.36- 1.27 (m, 3H), 1.15 (dd, J= 7.2 Hz, 18H), 0.40 (s, 9H).13C NMR (101 MHz, CDCh) 6 149.57, 143.50, 143.33, 141.54, 141.14, 140.73, 137.17, 131.11, 130.74, 130.52, 130.45, 127.54, 123.42, 122.87, 121.94, 118.20, 118.15, 112.30, 109.97, 100.33, 99.77, 99.66, 99.60, 98.23, 97.94, 94.69, 56.09, 26.21, 26.08, 18.13, 12.97, -0.76. HRMS: Calcd. for C43H55N2NaO6Si2 [M+Na]+= 788.3522 m / z, found = 788.3510 m / z. R / = (EtOAc / hexanes, 1:9) 0.33. IR (neat) v = 3452, 2940, 2863, 1479, 1446, 1303, 1197, 985, 835, 754, 659, 406 cm'1.

[0133] Compound 3, 69% (NMR yield calculated using hexamethylbenzene as an internal standard), light yellow solid. The reaction was carried out according to the General Procedure 1, the reaction was performed in THF / H2O at 60 °C for 1.5 h. Reagents: compound 7 (352.5 mg, 0.43 mmol, 1.1 equiv), compound 6a (151.0 mg, 0.39 mmol, 1.0 equiv), Pd(OAc)2(4.38 mg, 0.019 mmol, 5 mol %), SPhos (8.81 mg, 0.042 mmol, 5.5 mol %), K3PO4(173.9 mg, 0.82 mmol, 2.1 equiv), THF (8.0 mL), and H2O (2.0 mL). Purification: 10%WSGR Docket No. 63230-734.601EtOAc in hexanes.

[0134] 1HNMR(500MHz, CDCh) 6 10.12 (s, 1H), 9.95 (s, 1H), 9.06 (s, 1H), 8.50 (s, 1H), 7.14 (s, 1H), 7.03 (s, 1H), 6.99 (s, 1H), 6.93 (s, 1H), 6.93 (s, 1H), 6.87-6.88 (m, 2H), 6.81 (d, J= 2.1 Hz, 1H), 6.70 (d, J=2.1 Hz, 1H), 3.91 (s, 3H), 1.90 (s, 6H), 1.87 (s, 6H), 1.84 (s, 6H), 1.37-1.29 (m, 3H), 1.16 (d, J= 7.4 Hz, 18H), 0.40 (s, 9H). R / = (EtOAc / hexane, 1:9) 0.30.

[0135] 4, 68% (39.2 mg, 0.034 mmol), light yellow solid. The reaction was carried out according to the General Procedure 1, the reaction was performed in THF / H2O at 60 °C for 1.5 h. Reagents: compound 8 (55.8 mg, 0.055 mmol, 1.1 equiv), compound 6a (19.4 mg, 0.05 mmol, 1.0 equiv), Pd(OAc)2(0.56 mg, 0.0025 mmol, 5 mol %), SPhos (1.13 mg, 0.00275 mmol, 5.5 mol %), K3PO4(22.3 mg, 0.11 mmol, 2.1 equiv), THF (2.0 mL), H2O (0.5 mL). Purification: 10% to 20% EtOAc in hexanes.

[0136] 'H NMR (500 MHz, CDCh) 8 10.13 (d, = 2.2 Hz, 1H), 10.07 (d, J= 2.3 Hz, 1H), 9.97 (d, J= 2.2 Hz, 1H), 9.06 (d, J= 2.2 Hz, 1H), 8.50 (brs, 1H), 7.14 (s, 1H), 7.04 (s, 1H), 7.00 (s, 1H), 6.96 (s, 1H), 6.94 (m, 2H), 6.92 (d, J= 2.2 Hz, 2H), 6.89 (d, J= 2.1 Hz, 1H), 6.82 (d, J= 22 Hz, 1H), 6.70 (d, J= 2.1 Hz, 1H), 3.91 (s, 3H), 1.91 (s, 6H), 1.90 (s, 6H), 1.87 (s, 6H), 1.84 (s, 6H), 1.37 - 1.29 (m, 3H), 1.16 (d, J= 7.5 Hz, 18H), 0.40 (s, 9H). °C NMR (101 MHz, CDCh) 6 149.61, 143.59, 143.55, 143.32, 141.58, 141.16, 140.81, 140.78, 140.75, 137.21, 131.14, 130.97, 130.84, 130.59, 130.47, 127.50, 127.20, 127.12, 123.46, 123.21, 123.14, 122.97, 121.96, 118.38, 118.36, 118.31, 118.22, 112.33, 109.98, 100.45, 100.14, 100.08, 99.86, 99.73, 99.69, 99.59, 99.56, 98.33, 98.20, 97.84, 97.67, 94.70, 56.08, 26.26, 26.24, 26.21, 26.17, 18.14, 12.98, -0.76. HRMS: Calcd. for C₆₅H₇₃N₅NaO₁₀Si₂ [M+Na]+= 1162.4788 m / z, found = 1162.4802 m / z. R / = (EtOAc / hexanes, 2:8) 0.47.WSGR Docket No. 63230-734.601Example B-2: Ir-catalyzed Borylation of IndolesOR6

[0137] General Procedure 2: In an inert atmosphere glove box, a flamed-dried vial equipped with a Teflon-coated stir bar was charged with indole (1.0 equiv) and dry, degassed solvent (THF, cyclohexane). In three separate flamed-dried vials bispinacolatodiboron (B2pin2, 1.0 - 2.0 equiv), 4, 4'-di- / c / 7-buty 1-2, 2'-bi pyridyl (dtbpy, 3.0 - 14.0 mol%), and [Ir(COD)(OMe)]2 (1.5— 7.0 mol%) were dissolved in dry, degassed solvent (THF, cyclohexanes). The solution of B₂pin₂ was added to the solution of [Ir(COD)OMe]₂ followed by the addition of dtbpy. The mixture was stirred in the glovebox for 0.5 h before the addition of the indole solution. The vial was sealed and heated to the indicated temperature in a pre-heated oil bath outside of the glove box. After the indicated time, the reaction was cooled to r.t. and transferred to a round-bottom flask using CH₂Cl₂ to wash the tube. The reaction was concentrated in vacuo and purified via column chromatography to yield the corresponding borylated indole using the indicated solvent system.

[0138] Compounds 5 to 8 were synthesized according to General Procedure 2 with appropriate reagents and intermediates.HNMe3Si

[0139] 5, 83% (3.2 g, 8.3 mmol), light yellow solid. The reaction was carried out according to the General Procedure 2 and was performed in cyclohexanes at room temperature for 40 min. Reagents: compound 4a (2.6 g, 10 mmol, 1.0 equiv), [Ir(OMe)(COD)]2 (99.43 mg, 0.15 mmol, 1.5 mol%), dtbpy (80.52 mg, 0.30 mmol, 3.0 mol%), B2pin2(2.5 g, 10 mmol, 1.0 equiv), and Cyclohexanes (25 mL, 0.4M). Purification: 10% EtOAc in hexanes.

[0140] 'H NMR (500 MHz, CDCh) 89.24 (brs, 1H), 6.98 (s, 1H), 6.56 (d, J= 2.3 Hz, 1H), 1.70 (s, 6H), 1.40 (s, 12H), 0.32 (s, 9H).13C NMR (126 MHz, CDCh) 6 151.78, 142.87, 138.35, 135.34, 121.11, 117.30, 110.54, 102.04, 83.71, 26.00, 25.13, -0.88.; HRMS: Calcd. for C20H31O4NBSi [M+H]+=388.21099 m / z, found =388.21015 m / z. R / = (EtOAc / hexanes, 1:9) 0.50.WSGR Docket No. 63230-734.601IR (neat) v = 3441, 2982, 2954, 1613, 1452, 1385, 1289, 1194, 1137, 1104, 1061, 991, 836, 754, 667, 628 cm'1.TIPSOMeO6, 94% (540.9 mg, 0.85 mmol), light yellow solid. The reaction was carried out according to the General Procedure 2 and was performed in THF at 60 °C for 1 h. Reagents: compound 9 (456.05 mg, 0.9 mmol, 1.0 equiv), [Ir(OMe)(COD)]2 (17.89 mg, 0.027 mmol, 3.0 mol%), dtbpy (14.49 mg, 0.054 mmol, 6.0 mol%), B₂pin₂ (228.54 mg, 0.9 mmol, 1.0 equiv), and THF (18 mL, 0.05 M). Purification: 10% EtOAc in hexanes.

[0142] XH NMR (500 MHz, CDCh) 58.98 (s, 1H), 8.90 (s, 1H), 7.18 (s, 1H), 7.04 (d, J= 2.1 Hz, 1H), 6.94 (s, 1H), 6.89 (s, 1H), 6.82 (d, J= 2.2Hz, 1H), 3.88 (s, 4H), 1.78 (s, 6H), 1.38 (s, 12H), 1.36 - 1.28 (m, 3H), 1.14 (d, J= 7.4 Hz, 18H).13C NMR (126 MHz, CDCh) 8 149.43, 143.50, 142.21, 141.36, 131.20, 130.82, 130.09, 122.98, 121.82, 118.17, 115.02, 110.22, 100.57, 100.56, 99.80, 98.38, 94.45, 84.15, 55.87, 26.16, 24.90, 18.15, 12.99. HRMS: Calcd. for C35H48N2O6BSi [M-H]+= 631.3380 m / z, found = 631.3393 m / z. R / = (EtOAc / hexanes, 8:2) 0.54. IR (neat) v = 3446, 2940, 2863, 1525, 1479, 1259, 1218, 1135, 852, 680 cm'1.TIPSOMeO

[0143] ' 7, 83% (350.2 mg, 0.43 mmol), light yellow solid. The reaction was carried out according to the General Procedure 2 and was performed in THF at 60 °C for 1 h. Reagents: compound 10 (353.8 mg, 0.5 mmol, 1.0 equiv), [Ir(OMe)(COD)]2 (10.14 mg, 0.015 mmol, 3.0 mol%), dtbpy (8.21 mg, 0.03 mmol, 6.0 mol%), B₂pin₂ (129.5 mg, 0.5 mmol, 1.0 equiv), and THF (10 mL, 0.05 M). Purification: 20% EtOAc in hexanes.

[0144] 'H NMR (400 MHz, CDCh) 6 10.03 (s, 1H), 9.04 (s, 1H), 8.87 (s, 1H), 7.11 (s, 1H), 7.07 (d, J= 2.1 Hz, 1H), 7.00 (s, 1H), 6.98 (s, 1H), 6.93 (s, 1H), 6.90 (d, J= 2.2 Hz, 1H), 6.84 (d,WSGR Docket No. 63230-734.6011H), 3.89 (s, 3H), 1.85 (s, 6H), 1.83 (s, 6H), 1.39 (s, 12H), 1.36- 1.27 (m, 3H), 1.14 (d, J= 7.3 Hz, 18H);13CNMR(101 MHZ, CDCh) 5 149.53, 143.57, 143.43, 142.12, 141.52, 140.73, 131.11, 130.56, 130.42, 130.34, 127.53, 123.20, 122.86, 121.96, 118.30, 118.17, 114.96, 109.96, 100.69, 99.75, 99.69, 99.57, 98.65, 98.01, 94.69, 84.20, 56.08, 26.22, 26.16, 24.97, 18.13, 12.97. HRMS: Calcd. for C46H57N3O8BSi [M-H]+= 818.40135 m / z, found = 818.40014 m / z. R / = (EtOAc / hexanes, 2:8) 0.39; IR (neat) v = 3453, 2935, 2863, 1299, 1261, 1216, 1197, 1135, 852, 661, 464 cm'1.TIPSOMeO8, 70% (55.8 mg, 0.055 mmol), light yellow solid. The reaction was carried out according to the General Procedure 2 and was performed in THF at 60 °C for 6 h. Reagents: compound 11 (72.2 mg, 0.08 mmol, 1.0 equiv), [Ir(OMe)(COD)]2 (1.59 mg, 0.0024 mmol, 3.0 mol%), dtbpy (1.29 mg, 0.0048 mmol, 6.0 mol%), B₂pin₂ (20.32 mg, 0.08 mmol, 1.0 equiv), and THF (1.6 mL, 0.05 M). Purification: 20% EtOAc in hexanes.

[0146] 'H NMR (500 MHz, CDCh) 8 10.12 (brs, 1H), 9.98 (brs, 1H), 9.06 (brs, 1H), 8.91 (brs, 1H), 7.13 (s, 1H), 7.08 (d, J= 2.0 Hz, 1H), 7.05 (s, 1H), 6.99 (s, 1H), 6.95 - 6.93 (m, 2H), 6.92 (s, 1H), 6.89 - 6.87 (m, 2H), 3.90 (s, 3H), 1.90 (s, 6H), 1.88 (s, 6H), 1.84 (s, 6H), 1.40 (s, 12H), 1.36 - 1.29 (m, 3H), 1.16 (d, J= 7.4 Hz, 18H).13C NMR (126 MHz, CDCh) 6 149.58, 143.56, 143.51, 143.49, 142.14, 141.56, 140.76, 140.72, 131.14, 130.68, 130.55, 130.49, 130.44, 127.47, 127.18, 123.24, 123.12, 122.97, 121.98, 118.36, 118.27, 118.25, 115.02, 109.97, 100.87, 99.97, 99.86, 99.71, 99.67, 99.54, 98.72, 98.20, 97.65, 94.71, 84.21, 56.08, 26.28, 26.22, 26.15, 24.97, 18.13, 12.98, 1.18. HRMS: Calcd. for C₅₇H₆₈N₄O₁₀BSi [M+H]+= 1007.47923 m / z, found = 1007.47881 m / z. R / = (EtOAc / hexanes, 2:8) 0.43. IR (neat) v = 3446, 2962, 2861, 1303, 1259, 1014, 854, 796, 663, 435 cm'1.Example B-3: Desilylation of IndolesWSGR Docket No. 63230-734.601OR6PPTS (1.2 equiv) rt MeOH and / or THF

[0147] General Procedure 3: A flame-dried round bottom flask, equipped with a Teflon coated stir bar, was charged with starting indole (1.0 equiv) followed by pyridinium p-toluenesulfonate (PPTS) (1.2 equiv). The flask was evacuated and backfilled with N2 (this process was repeated three times), then dry, degassed MeOH solvent was added under a positive N2 pressure. The resulting reaction mixture was then stirred at ambient temperature for indicated time, as monitored by thin-layer chromatography (TLC). After the addition of water (30 mL) and EtOAc (30 mL), the aqueous layer was extracted with EtOAc (3 x 20 mL). The combined organic layers were washed with brine (20 mL), dried over MgSO4, and concentrated in vacuo. The resulting residue was purified by flash chromatography on silica gel using the indicated solvent system as eluent to afford the desired product.

[0148] Compounds 9 to 12 were synthesized according to General Procedure 3 with appropriate reagents and intermediates.

[0149] 9, 99% (456.05 mg, 0.90 mmol), off-white solid. The reaction was carried out according to the General Procedure 3 and was performed in MeOH at ambient temperature for 3 h. Reagents: compound 1 (528.5 mg, 0.91 mmol, 1.0 equiv), PPTS (228.7 mg, 0.91 mmol, 1.0 equiv), and MeOH (10.0 mL). Purification: 10% EtOAc in hexanes.

[0150] 1HNMR(500MHz, CDCh) 58.99 (s, 1H), 8.60 (s, 1H), 7.16 (t, J= 2.8 Hz, 1H), 7.13 (s, 1H), 6.95 (s, 1H), 6.92 (s, 1H), 6.74 (d, J= 2.1 Hz, 1H), 6.49 (dd, J= 3.2, 2.1 Hz, 1H), 3.88 (s, 3H), 1.79 (s, 6H), 1.32 (sep, J= 6.9 Hz, 3H), 1.14 (d, J= 7.5 Hz, 18H).13C NMR (126 MHz, CDCh) 8 149.49, 143.20, 141.47, 140.74, 131.13, 130.45, 127.53, 122.95, 122.20, 121.81, 117.99, 110.14, 103.48, 99.98, 98.43, 94.56, 56.00, 26.18, 18.16, 18.16, 13.01. HRMS: Calcd. for C29H3sN2O4Si [M-H]+= 505.2528 m / z, found = 505.2536 m / z. R / = (EtOAc / hexanes, 1:9) 0.34; IR (neat) v = 3444, 2939, 2863, 1479, 1299, 1186, 987, 852, 676, 414 cm'1.WSGR Docket No. 63230-734.601TIPSOMeO

[0151] 10, 84% (384.71 mg, 0.55 mmol), off-white solid. The reaction was carried out according to the General Procedure 3 and was performed in MeOH at ambient temperature for 3 h. Reagents: compound 2 (509.5 mg, 0.66 mmol, 1.0 equiv), PPTS (199.03 mg, 0.79 mmol, 1.2 equiv), and MeOH (13.0 mL, 0.05 M). Purification: 10% EtO Ac in hexanes.

[0152] 'H NMR (500 MHz, CDCh) 6 10.05 (s, 1H), 9.04 (s, 1H), 8.57 (s, 1H), 7.20 (dd, J= 3.1, 2.4 Hz, 1H), 7.12 (s, 1H), 6.98 (s, 1H), 6.95 (s, 1H), 6.94 (s, 1H), 6.84 (dd, J= 3.1, 2.3 Hz, 1H), 6.80 (d, J= 2.3 Hz, 1H), 6.52 (dd, J= 3.1, 2.0 Hz, 1H), 3.89 (s, 3H), 1.85 (s, 6H), 1.82 (s, 6H), 1.28-1.35 (m, 3H), 1.15 (d, = 7.4Hz, 18H). °C NMR (126 MHz, cdcl3) 5 149.55, 143.45, 143.28, 141.54, 140.73, 140.71, 131.11, 130.55, 130.53, 127.47, 127.21, 123.13, 122.84, 122.44, 121.97, 118.19, 118.09, 109.97, 103.61, 100.26, 99.92, 99.78, 99.61, 98.62, 97.89, 94.70, 56.09, 26.21, 26.11, 18.13, 12.98. HRMS: Calcd. for C40H48N3O6 [M+H]+= 694.33069 m / z, found = 394.32955 m / z. R / = (EtOAc / hexanes, 8:2) 0.2. IR (neat) v = 3450, 2939, 2863, 1446, 1301, 1197, 985, 883, 852, 661, 435 cm'1.TIPSOMeO

[0153] 11, 60% over two steps (206.18 mg, 0.23 mmol), off-white solid. The reaction was carried out according to the General Procedure 3 and was performed in MeOH and THF at ambient temperature for 6 h. Reagents: compound 3 (390.0 mg, 0.40 mmol, 1.0 equiv), PPTS (120.6 mg, 0.48 mmol, 1.2 equiv), MeOH (10 mL), and THF (2 mL). Purification: 10% EtO Ac in hexanes.WSGR Docket No. 63230-734.601

[0154] XH NMR (500 MHz, CDCh) 5 10.11 (s, 1H), 10.00 (s, 1H), 9.05 (s, 1H), 8.59 (s, 1H), 7.20 (dd, 3.2, 2.2 Hz 1H), 7.13 (s, 1H), 6.99 (m, 2H), 6.96 (s, 1H), 6.92 (s, 1H), 6.87-6.88 (m, 2H), 6.83 (d, J= 2.2 Hz, 1H), 6.52 (dd, J= 3.2, 2.1 Hz, 1H), 3.90 (s, 3H), 1.89 (s, 6H), 1.87 (s, 6H), 1.83 (s, 6H), 1.36- 1.29 (m, 3H), 1.15 (d, J= 7.4 Hz, 18H).13C NMR (126 MHz, CDCh) 8 149.60, 143.52, 143.28, 141.57, 140.78, 140.74, 140.72, 131.13, 130.77, 130.64, 130.49, 127.47, 127.24, 127.13, 123.15, 123.10, 122.96, 122.47, 121.97, 118.29, 118.16, 109.98, 103.64, 100.42, 100.00, 99.85, 99.71, 99.59, 98.70, 98.07, 97.66, 94.70, 56.09, 26.24, 26.15, 18.14, 12.98. HRMS: Calcd. for C51H55N4O8Si [M-H]+= 879.37946 m / z, found = 879.37924 m / z. R / = (EtOAc / hexanes, 1:9) 0.23. IR (neat) v = 34550, 2937, 2863, 1446, 1303, 1199, 1170, 983, 850, 754, 661, 435 cm'1.TIPSOMeO12, 89% (206.18 mg, 0.03 mmol), off-white solid. The reaction was carried out according to the General Procedure 3 and was performed in MeOH and THF at ambient temperature for 6 h. Reagents compound 27 (39.2 mg, 0.034 mmol, 1.0 equiv), PPTS (10.3 mg, 0.041mmol, 1.2 equiv), MeOH (2 mL), and THF (0.2 mL). Purification: 20% EtOAc in hexanes.

[0156] XH NMR (500 MHz, CDCh) 6 10.12 (d, J= 2.2 Hz, 1H), 10.08 (d, J= 2.2 Hz, zlH), 10.01 (d,.7= 2.0 Hz, 1H), 9.06 (d, = 2.1 Hz, 1H), 8.59 (brs, 1H), 7.21 (dd, J= 3.1, 2.4 Hz, 1H), 7.14 (s, 1H), 6.99 (s, 2H), 6.96 (s, 2H), 6.94 (s, 1H), 6.91 (m, 2H), 6.88 (d, J= 2.1 Hz, 1H), 6.84 (d,.7= 2.2 Hz, 1H), 6.53 (dd, J= 3.1, 2.1 Hz, 1H), 3.90 (s, 3H), 1.91 (s, 6H), 1.90 (s, 6H), 1.88 (s, 6H), 1.84 (s, 6H), 1.37 - 1.28 (m, 3H), 1.16 (d, J= 7.4 Hz, 18H).13C NMR (201 MHz, CDCh) 6 149.61, 143.59, 143.55, 143.51, 143.28, 141.58, 140.81, 140.77, 140.75, 131.14, 130.86, 130.79, 130.60, 130.47, 127.50, 127.24, 127.15, 127.12, 123.22, 123.15, 123.13, 122.97, 122.48, 121.97, 118.38, 118.35, 118.31, 118.17, 109.98, 103.64, 100.43, 100.14, 100.08, 99.88, 99.86, 99.73, 99.69, 99.55, 98.71, 98.15, 97.84, 97.67, 94.70, 56.09, 26.27, 26.26, 26.24, 26.17, 18.14, 12.99.WSGR Docket No. 63230-734.601HRMS: Calcd. for C62H65N5NaO10Si [M+Na]+= 1090.4393 m / z, found = 1090.4346 m / z. R / = (EtOAc / hexanes, 2:8) 0.14. IR (neat) v = 3444, 2935, 2863, 1446, 1303, 1199, 1170, 983, 852, 755, 663 cm'1.Example C-l: Spectroscopic Studies

[0157] Materials: Acetonitrile (> 99%) and cyclohexane (99.8%) were purchased from Thermo Scientific (USA). Sulfuric acid (95.0-98.0%) and quinine hemisulfate salt monohydrate (QS) were purchased from Sigma- Aldrich (USA). 5,6-Dihydroxyindole (DHI) was purchased from Chem-Impex International (USA). Poly ethersulfone (PES) syringe filters were manufactured by Sartorius (Germany) and purchased from Fisher Scientific.

[0158] Sample preparation: All samples were prepared by dissolving solutes in airequilibrated solvents at room temperature. The commercial DHI sample was dissolved in ultrapure water and then filtered through a 0.22 pm PES filter. Absorption spectra were recorded with a Cary 5000 (UV / Vis / NIR) spectrometer (Agilent, USA) in the dual beam mode using solutions held in a 1 cm path length fused silica cuvette. Emission and excitation spectra were recorded from solutions held in a 1 cm path length fused silica cuvette using a QuantaMaster 8000 Fluorimeter (Horiba, USA). Luminescence spectra were collected in the standard 90° geometry and emitted photons were detected with a photomultiplier tube. Spectra were acquired using a step size of 1 nm and a detector integration time of 0.2 s. The emission and excitation slits were 1 nm. The OMe JL^OTIPSexcitation wavelength was 285 nm for the monomers(S9) and la and 295 nm for the oligomers. The excitation wavelength for 5,6-DHI was 275 nm. Fluorescence quantum yields were estimated using quinine sulfate (QS) in 0.5 M sulfuric acid as a standard (Φf= 0.546) and results shown in Table 1. Results from other spectroscopic studies are depicted in Table 2, Table 3, and Table 4.

[0159] As shown in FIG. 1, absorption and emission spectra of monomer S9 and monomer la in acetonitrile and cyclohexane were collected (top and middle panels, respectively). Absorption and emission spectra of DHI in aqueous solution was also collected (bottom panel). Absorption and emission spectra are shown by dashed and solid curves, respectively.

[0160] As shown in FIG.2, absorption and emission spectra in acetonitrile and cyclohexane of dimer 9, trimer 10, tetramer 11, and pentamer 12 were collected. Absorption and emission spectra are shown by dashed and solid curves, respectively.

[0161] As shown in FIG.3 (top panel), wavelength of the 0-0 vibronic emission peak maximum as an estimate of the electronic origin (gray circles) vs. the number of acetonide-WSGR Docket No. 63230-734.601protected monomers, n, was collected. The solid curve is a fit to the model from Meier, U.Stalmach, H. Kolshorn, Acta Polym. 1997, 48, 379-384. Absorption peak maxima vs. the number of repeating units for oligo(l,4-phenylene) in THF (middle panel) and oligo(aryleneethenylene) in THF (bottom panel). Data in the middle and bottom panels are from H. For each graph, the asymptotic estimate of the absorption onset for the infinitely long polymer (λ∞) is shown;

[0162] As shown in FIG. 4, absorption spectra of monomer S9, dimer 9, and trimer 10 measured in cyclohexane (C6H12) or acetonitrile (CH3CN), as indicated. Spectra were recorded from freshly prepared solutions (black curves) and from the same solutions 20 months later (gray curves).

[0163] As shown in FIG. 5, absorption spectra of monomer S9, dimer 9, trimer 10, tetramer 11, and pentamer 12 in acetonitrile before (black curves) and after (gray curves) irradiation for 30 minutes by 100 fs laser pulses (1 kHz pulse repetition rate; incident energy density 170 μJ cm-2; center wavelength of 300 nm for the monomer and dimer, 315 nm for the trimer, tetramer, and pentamer) were collected.

[0164] As shown in FIG. 6 (top panel), extinction spectrum of dimer 9 (gray curve) compared with the sum of the extinction spectrum of monomer la plus the extinction spectrum of monomer S9 (black curve) was collected. (Middle panel) Extinction spectrum of trimer 10 (dark gray curve) was compared with the sum of twice the extinction spectrum of monomer la plus the extinction spectrum of monomer S9 (light gray curve). (Bottom panel) Extinction spectra of monomers S9 (gray curve) and la (light gray curve) were collected. All spectra were recorded in cyclohexane solution and extinction values are believed to be accurate to within 10%.

[0165] As shown in FIG. 7, normalized emission spectra of dimer 9, trimer 10, tetramer 11 and pentamer 12 in cyclohexane. The latter three curves were shifted along the frequency axis to align the long wavelength emission band with that of the dimer.Table 1. Fluorescence quantum yields, < I (%), of the monomers and oligomers in acetonitrile.Compound S9 la 9 10 11 12 DHF 35 ± 3 33 ± 3 49 ± 1 46 ± 2 42 ± 2 37 ± 2 <1asolvent: water.WSGR Docket No. 63230-734.601Table 2. Emission peak positions of the monomers and oligomersPeak positions in Iem(ṽ) (cm-1)aPeak positions in Iem(λ) (nm)Acetonitrile (CH3CN)S9 30500 326la 29600 3389 27400 26200 24800 367 381 405 Δṽem1200 140010 25600 24400 23000 390 408 436 Δṽem1200 140011 25400 24200 22800 21300 393 413 439 467 Δṽem1200 1400 150012 25400 24000 22600 394 414 442 Δṽem1400 1400Cyclohexane (C6H12)S9 32200 31500 30700 312 317 325 Δṽem700 800la 31300 30600 29900 29200 320 327 335 343 Δṽem700 700 7009 27800 26300 24900 23500 360 380 402 428 Δṽem1500 1400 140010 26000 24600 23200 21600 385 407 431 457 Δṽem1400 1400 160011 25600 24300 22900 21400 390 413 438 467 Δṽem1300 1400 150012 25500 24100 22700 21100 392 414 440 471 Δṽem1400 1400 1600“Emission spectra recorded vs. wavelength, Iem( ), were multiplied by A2to obtain Iem( = 1 / A).WSGR Docket No. 63230-734.601Table 3. Long wavelength absorption peak in the indicated solvents.Compound λ0-0(nm) in CH3CN λ0-0(nm) in C6H12S9 307 307la 310 3169 353 35410 353 37711 382 38312 382 386Table 4. Emission peak intensity ratio of the first two emission subbands of the oligomers.I0-1(ṽ) / I0-0(ṽ) Compound SolventCH3CN 1.39CeHu 0.95CH3CN 1.210CeHu 0.92CH3CN 1.111CeHu 0.75CH3CN 1.112CeHu 0.64

Claims

WSGR Docket No. 63230-734.601CLAIMS WHAT IS CLAIMED IS:

1. A compound represented by the structure of Formula (I):or a pharmaceutically acceptable salt thereof, wherein:is selected from:hydrogen, halogen, Ci-6 alkyl, -Si(R20)3, -B(R21)2,each R1is independently selected from hydrogen, Ci-6 alkyl, -C(O)R23, and -C(O)OR23; each R2is independently selected from hydrogen, halogen, Ci-6 alkyl, -Si(R20)3, and -B(R21)2; each R3is independently selected from hydrogen and Ci-6 alkyl;each R4is independently selected from hydrogen and Ci-6 alkyl;each R5and R6are independently selected from hydrogen, -Si(R20)3, and Ci-6 alkyl; or one R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl;R7is selected from hydrogen, halogen, Ci-6 alkyl, and -B(R21)2;each R20is independently selected from Ci-6 alkyl;each R21is independently selected from -OR22;each R22is independently selected from hydrogen and Ci-6 alkyl; orWSGR Docket No. 63230-734.601two R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl;each R23is independently selected from C1-6 alkyl which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, -N(CI-6 alkyl)2, Ci-6 alkyl, -C1-6haloalkyl, and -O-Ci-6 alkyl; andm is selected from 1 to 20.The compound or salt of claim 1, whereinis selected from hydrogen, -Si(R20)3, -The compound or salt of claim 1 or claim 2, whereinis selected from hydrogen, - Si(R20)3, and -B(R21)2.The compound or salt of claim 1 or claim 2, whereinis selected from5. The compound or salt of any one of claims 1 to 4, wherein each R1is independently selected from hydrogen, -C(O)R23, and -C(O)OR23.

6. The compound or salt of any one of claims 1 to 5, wherein each R1is independently selected from hydrogen and -C(O)OR23.

7. The compound or salt of any one of claims 1 to 6, wherein each R1is independently selected from hydrogen.

8. The compound or salt of any one of claims 1 to 7, wherein each R2is independentlyWSGR Docket No. 63230-734.601selected from hydrogen, Ci-6 alkyl, -Si(R20)3, and -B(R21)2.

9. The compound or salt of any one of claims 1 to 8, wherein each R2is independently selected from hydrogen, -Si(R20)3, and -B(R21)2.

10. The compound or salt of any one of claims 1 to 9, wherein each R2is independently selected from hydrogen, -Si(Me)3, and -Bpin.

11. The compound or salt of any one of claims 1 to 10, wherein each R3is independently selected from hydrogen and Ci-4 alkyl.

12. The compound or salt of any one of claims 1 to 11, wherein each R3is independently selected from hydrogen.

13. The compound or salt of any one of claims 1 to 12, wherein each R4is selected from hydrogen and Ci-4 alkyl.

14. The compound or salt of any one of claims 1 to 13, wherein each R4is selected from hydrogen.

15. The compound or salt of any one of claims 1 to 14, wherein R7is selected from hydrogen, halogen, and -B(R21)2.

16. The compound or salt of any one of claims 1 to 15, wherein R7is selected from hydrogen, bromo, iodo, and -B(R21)2.

17. The compound or salt of any one of claims 1 to 16, wherein R7is selected from hydrogen, iodo, -B(R21)2.

18. The compound or salt of any one of claims 1 to 17, wherein each R5and R6are independently selected from -Si(R20)3 and Ci-6 alkyl; orone R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl.

19. The compound or salt of any one of claims 1 to 18, wherein each R5and R6are independently selected from -Si(R20)3, and Ci-6 alkyl; orone R5and one R6are taken together to form a heterocycle which is optionally and independently substituted with one or more Ci-4 alkyl.

20. The compound or salt of any one of claims 1 to 19, wherein each R20is independently selected from Ci-4 alkyl.

21. The compound or salt of any one of claims 1 to 20, wherein each R22is independently selected from hydrogen; ortwo R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl.WSGR Docket No. 63230-734.60122. The compound or salt of any one of claims 1 to 21, wherein two R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle, which is optionally substituted with one or more substituents independently selected from Ci-6 alkyl.

23. The compound or salt of any one of claims 1 to 22, wherein Formula (I) is represented by the structure of Formula (I- A):Formula (I- A);or a pharmaceutically acceptable salt thereof.

24. The compound or salt of any one of claims 1 to 22, wherein Formula (I) is represented by the structure of Formula (I-B):or a pharmaceutically acceptable salt thereof.

25. The compound or salt of any one of claims 1 to 22, wherein Formula (I) is represented by the structure of Formula (I-C):or a pharmaceutically acceptable salt thereof, wherein:m is selected from 1 to 20.WSGR Docket No. 63230-734.60126. The compound or salt of any one of claims 1 to 25, wherein the compound is selected from:TIPSOTIPSOWSGR Docket No. 63230-734.601TIPSOTIPSOpharmaceutically acceptable salt of any one thereof.

27. A process for the preparation of a compound represented by the structure of Formula (II):WSGR Docket No. 63230-734.601comprising a suitable cross-coupling reaction of:(i) contacting a compound represented by the structure of Formula (II- A) or Formula (II-A*):Formula (II- A*); wherein,each G1is independently a suitable boryl moiety;(ii) with a compound represented by the structure of Formula (II-B):Formula (II-B);wherein,X is a suitable halide;in the presence of a suitable solvent to afford a compound represented by the structure of Formula (II), or a pharmaceutically acceptable salt thereof, wherein:each R1is independently selected from hydrogen, Ci-6 alkyl,, -C(O)R23, and -WSGR Docket No. 63230-734.601C(O)OR23;each R2is independently selected from hydrogen, halogen, Ci-6 alkyl, -Si(R20)3, and -B(R21)2;each R3is independently selected from hydrogen and Ci-6 alkyl;each R4is independently selected from hydrogen and Ci-6 alkyl;each R5and R6are independently selected from hydrogen, -Si(R20)3, and Ci-6 alkyl; orone R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl;each R7is independently selected from hydrogen, halogen, Ci-6 alkyl, and - B(R21)2;each R20is independently selected from Ci-6 alkyl;each R21is independently selected from -OR22;each R22is independently selected from hydrogen and Ci-6 alkyl; or two R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl;each R23is independently selected from Ci-6 alkyl which is optionally substituted with one or more substituents independently selected from halogen, -OH, - CN, -NO2, -NH2, -N(CI-6 alkyl)2, Ci-6 alkyl, -C1-6haloalkyl, and -O-Ci-6 alkyl; andeach m is independently selected from 0 to 20.

28. The process of claim 27, wherein the suitable cross-coupling reaction comprises a suitable transition metal complex.

29. The process of claim 28, wherein the suitable transition metal complex comprises a suitable nickel complex, a suitable copper complex, a suitable palladium complex, or suitable combinations thereof.

30. The process of claim 28 or claim 29, wherein the suitable transition metal complex comprises a suitable palladium complex.

31. The process of claim 30, wherein the suitable palladium complex comprises a suitable palladium precursor and a suitable ligand.

32. The process of claim 31, wherein the suitable palladium precursor is selected from Pd(trifluoroacetate)2, Pd(OAc)2, [Pd(OAc)2]3, PdCl2, Pd(PPh3)4, Pd(PPh3)2Cl2,WSGR Docket No. 63230-734.601Pd(acac)2, Pd(dibenzylideneacetone)2, Pd2(dibenzylideneacetone)3, allylpalladium chloride dimer, Palladium(π-cinnamyl) chloride dimer, Bis(benzonitrile)palladium chloride, and Pd(acetylacetonate)2.

33. The process of claim 31 or claim 32, wherein the suitable palladium precursor is selected from Pd(trifluoroacetate)2, Pd(OAc)2, and [Pd(OAc)2]3.

34. The process of any one of claims 31 to 33, wherein the suitable palladium precursor is Pd(OAc)2.

35. The process of claim 31, wherein the suitable ligand is selected from a suitable monodentate phosphine and a suitable bidentate phosphine.

36. The process of claim 31 or claim 35, wherein the suitable ligand is selected from a suitable monodentate phosphine.

37. The process of any one of claims 31, 35, or 36, wherein the suitable monodentate phosphine is selected from a suitable trialkyl-phosphine, a suitable tricycloalkylphosphine, a suitable dialkylaryl-phosphine, a suitable dicycloalkylaryl-phosphine, and a suitable triaryl-phosphine.

38. The process of any one of claims 31 or 35 to 37, wherein the suitable monodentate phosphine is selected from a suitable dialkylaryl-phosphine and a suitable dicycloalkylaryl-phosphine.

39. The process of claim 38, wherein the suitable dialkylaryl-phosphine and the suitable dicycloalkylaryl-phosphine is selected from SPhos, XPhos, MePhos, tBuMePhos, t- BuDavePhos, DavePhos, CyJohnPhos, JohnPhos, RuPhos, and suitable combinations thereof.

40. The process of claim 38 or claim 39, wherein the suitable dicycloalkylaryl-phosphine is selected from SPhos, RuPhos, and suitable combinations thereof.

41. The process of any one of claims 38 to 40, wherein the suitable dicycloalkylaryl- phosphine is SPhos.

42. The process of claim 30, wherein the suitable palladium complex comprises Pd(OAc)2 and SPhos.

43. The process of any one of claims 27 to 42, wherein each G1is independently selected from -B(R21a)2, wherein:each R21ais independently selected from -OR22a; andeach R22ais independently selected from hydrogen and Ci-6 alkyl; ortwo R22aon different O atoms are taken together with the O atom to which each R22ais attached to form a heterocycle which is optionally substituted with one orWSGR Docket No. 63230-734.601more substituents independently selected from CMO alkyl.

44. The process of any one of claim 27 to 43, wherein Ghs selected from -B(0H)2, - B(0Me)2, -B(O1Pr)2, -Bpin, and -Bneop.

45. The process of any one of claims 27 to 44, wherein G1is selected from -B(OH)2, -Bpin, and -Bneop.

46. The process of any one of claims 27 to 45, wherein G1moiety is -Bpin.

47. The process of any one of claims 27 to 46, wherein the suitable solvent is selected from toluene, benzene, THF, 1,4-di oxane, DMA, DMF, DMSO, MeCN, water, and suitable combinations thereof.

48. The process of any one of claims 27 to 47, wherein the suitable solvent is selected from toluene, THF, 1,4-di oxane, water, and suitable combinations thereof.

49. The process of any one of claims 27 to 48, wherein the suitable solvent is selected from THF, water, and suitable combinations thereof.

50. The process of any one of claims 27 to 49, wherein X is selected from chloro, bromo, and iodo.

51. The process of any one of claims 27 to 50, wherein X is selected from bromo and iodo.

52. The process of any one of claims 27 to 51, wherein X is iodo.

53. A process for the preparation of a compound represented by the structure of Formula (III) or Formula (III*):comprising a suitable desilylation reaction of:(i) contacting a compound represented by the structure of Formula (III- A) or Formula (III-A*):WSGR Docket No. 63230-734.601Formula (III- A*); wherein,each G2is independently a suitable silyl moiety;(ii) with a suitable desilylation reagent,in the presence of a suitable solvent to afford a compound represented by the structure of Formula (III) or Formula (III*), or a pharmaceutically acceptable salt of any one thereof, wherein:each R1is independently selected from hydrogen, Ci-6 alkyl,, -C(O)R23, and - C(O)OR23;each R2is independently selected from hydrogen, halogen, Ci-6 alkyl, -Si(R20)3, and -B(R21)2;each R3is independently selected from hydrogen and Ci-6 alkyl;each R4is independently selected from hydrogen and Ci-6 alkyl;each R5and R6are independently selected from hydrogen, -Si(R20)3, and Ci-6 alkyl; orone R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl;each R7is independently selected from hydrogen, halogen, Ci-6 alkyl, and - B(R21)2;each R20is independently selected from Ci-6 alkyl;each R21is independently selected from -OR22;each R22is independently selected from hydrogen and Ci-6 alkyl; ortwo R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl;WSGR Docket No. 63230-734.601each R23is independently selected from Ci-6 alkyl which is optionally substituted with one or more substituents independently selected from halogen, -OH, - CN, -NO2, -NH2, -N(Ci-6alkyl)2, Ci-6 alkyl, -C1-6haloalkyl, and -O-Ci-6 alkyl; andeach m is independently selected from 0 to 20.

54. The process of claim 53, wherein G2is selected from -Si(R20b)3, wherein each R20bis independently selected from Ci-6 alkyl.

55. The process of claim 53 or claim 54, wherein G2is selected from -Si(Me)3, -Si(Et)3, - Si(nbutyl)3, -Si(nhexyl)3, and -Si(1Pr)3.

56. The process of any one of claims 53 to 55, wherein G2is selected from -Si(Me)3 and - Si(Et)3.

57. The process of any one of claims 53 to 56, wherein G2is -Si(Me)3.

58. The process of any one of claims 53 to 57, wherein the suitable desilylation reagent is a suitable acid or a suitable fluoride reagent.

59. The process of any one of claims 53 to 58, wherein the suitable desilylation reagent is a suitable acid.

60. The process of claim 59, wherein the suitable acid is a suitable organic acid or a suitable inorganic acid.

61. The process of claim 60, wherein the suitable organic acid is selected from Pyridinium p-toluenesulfonate (PPTS), tetrabutylammonium p-toluenesulfonate, acetic acid, and trifluoroacetic acid.

62. The process of claim 59 or claim 60, wherein the suitable organic acid is Pyridinium p- toluenesulfonate (PPTS).

63. The process of any one of claims 53 to 58, wherein the suitable desilylation reagent is a suitable fluoride reagent.

64. The process of claim 63, wherein the suitable fluoride reagent is selected from tetrabutylammonium fluoride, LiF, NaF, KF, CsF, and RbF.

65. The process of any one of claims 53 to 64, wherein the suitable solvent is selected from MeOH, EtOH, 'PrOH, THF, 1,4-di oxane, MeCN, water, and suitable combinations thereof.

66. The process of any one of claims 53 to 65, wherein the suitable solvent is selected from MeOH, EtOH, THF, 1,4-di oxane, water, and suitable combinations thereof.

67. The process of any one of claims 53 to 66, wherein the suitable solvent is selected from MeOH, THF, and suitable combinations thereof.WSGR Docket No. 63230-734.60168. A process for the preparation of a compound represented by the structure of Formula (IV) or Formula (IV*):wherein,m is selected from 0 to 20;comprising a suitable borylation reaction of:(i) contacting a compound represented by the structure of Formula (IV-A) or Formula (IV-A*):Formula (IV-A*); (ii) with a suitable borylation reagent,in the presence of a suitable solvent to afford a compound represented by the structure of Formula (IV) or Formula (IV*), or a pharmaceutically acceptable salt of any one thereof, wherein:each R1is independently selected from hydrogen, Ci-6 alkyl, -C(O)R23, and - C(O)OR23;each R2is independently selected from hydrogen, halogen, Ci-6 alkyl, -Si(R20)3, and -B(R21)2;each R3is independently selected from hydrogen and Ci-6 alkyl;WSGR Docket No. 63230-734.601each R4is independently selected from hydrogen and Ci-6 alkyl;each R5and R6are independently selected from hydrogen, -Si(R20)3, and Ci-6 alkyl; orone R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl;each R7is independently selected from hydrogen, halogen, Ci-6 alkyl, and - B(R21)2;each R20is independently selected from Ci-6 alkyl;each R21is independently selected from -OR22;each R22is independently selected from hydrogen and Ci-6 alkyl; or two R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl; each R23is independently selected from Ci-6 alkyl which is optionally substituted with one or more substituents independently selected from halogen, -OH, - CN, -NO2, -NH2, -N(Ci-6alkyl)2, Ci-6 alkyl, -C1-6haloalkyl, and -O-Ci-6 alkyl; andeach m is selected from 0 to 20.

69. The process of claim 68, wherein the suitable borylation reaction comprises a suitable transition metal complex.

70. The process of claim 69, wherein the suitable transition metal complex comprises a suitable rhodium complex, a suitable iridium complex, a suitable iron complex, or suitable combinations thereof.

71. The process of claim 69 or claim 70, wherein the transition metal complex comprises a suitable iridium complex.

72. The process of claim 71, wherein the suitable iridium complex comprises a suitable iridium precursor and a suitable ligand.

73. The process of claim 72, wherein the suitable iridium precursor is selected (1,5- cyclooctadiene)(methoxy)iridium dimer, (l,5-cyclooctadiene)(chloro)iridium dimer, [(MeCN)2(l,5-cyclooctadiene)iridium]BF4, and 1,5- Cy cl ooctadi ene(acety 1 acetonato)iri dium.

74. The process of claim 72 or claim 73, wherein the suitable iridium precursor is (1,5- cyclooctadiene)(methoxy)iridium dimer.WSGR Docket No. 63230-734.60175. The process of claim 72, wherein the suitable ligand is selected from a suitable pyridine, a suitable bipyridine, and a suitable phenanthroline.

76. The process of claim 72 or claim 75, wherein the suitable ligand is selected from a suitable bipyridine.

77. The process of any one of claims 72, 75, or 76, wherein the suitable ligand is selected from 4,4'di- / c / 7-butyl-2,2'- bipyridine (dtbpy), 4,4'-dimethoxy-2-2'-bipyridine (4,4’- OMebpy), 4,4'-dimethylamino-2-2'-bipyridine (4,4’-NMe2bpy), and 4,4'-dimethyl-2,2'- bipyridine (4,4’-Mebpy).

78. The process of any one of claims 72 or 75 to 77, wherein the suitable ligand is selected from 4,4'di- / c 7-butyl-2,2'- bipyridine (dtbpy) and 4,4'-dimethoxy-2-2'-bipyridine (4,4’- OMebpy).

79. The process of any one of claims 72 to 77, wherein the suitable ligand is 4,4'di - / / 7- butyl-2,2'- bipyridine (dtbpy).

80. The process of any one of claims 68 to 79, wherein the suitable borylation reagent is selected from bis(catecholato)diboron (B2Cat2), bis(neopentyl glycolato)diboron (B2neop2), bis(pinacolato)diboron (B2pin2), Catecholborane (HBcat), 4, 4,5,5- Tetramethyl-l,3,2-dioxaborolane (HBpin).

81. The process of any one of claims 68 to 80, wherein the suitable borylation reagent is selected from bis(neopentyl glycolato)diboron (B2neop2), bis(pinacolato)diboron (B2pin2), and 4,4,5,5-Tetramethyl-l,3,2-dioxaborolane (HBpin).

82. The process of any one of claims 68 to 81, wherein the suitable borylation reagent is selected from bis(pinacolato)diboron (B2pin2) and 4,4,5,5-Tetramethyl-l,3,2- dioxaborolane (HBpin).

83. The process of any one of claims 68 to 82, wherein the suitable borylation reagent is bis(pinacolato)diboron (B2pin2).

84. The process of any one of claims 68 to 83, wherein the suitable solvent is selected from benzene, THF, 1,4-di oxane, and suitable combinations thereof.

85. The process of any one of claims 68 to 84, wherein the suitable solvent is THF.

86. The process of any one of claims 27 to 85, wherein each R1independently selected from hydrogen,, -C(O)R23, and -C(O)OR23.

87. The process of any one of claims 27 to 86, wherein each R1independently selected hydrogen and -C(O)OR23.

88. The process of any one of claims 27 to 86, wherein each R1independently selected from hydrogen.WSGR Docket No. 63230-734.60189. The process of any one of claims 27 to 88, wherein each R2is independently selected from hydrogen, Ci-6 alkyl, -Si(R20)3, and -B(R21)2.

90. The process of any one of claims 27 to 89, wherein each R2is independently selected from hydrogen, -Si(R20)3, and -B(R21)2.

91. The process of any one of claims 27 to 90, wherein each R2is independently selected from hydrogen, -Si(Me)3, and -Bpin.

92. The process of any one of claims 27 to 91, wherein each R3is independently selected from hydrogen and Ci-4 alkyl.

93. The process of any one of claims 27 to 92, wherein each R3is independently selected from hydrogen.

94. The process of any one of claims 27 to 93, wherein each R4is selected from hydrogen and Ci-4 alkyl.

95. The process of any one of claims 27 to 94, wherein each R4is selected from hydrogen.

96. The process of any one of claims 27 to 95, wherein R7is selected from hydrogen, halogen, and -B(R21)2.

97. The process of any one of claims 27 to 96, wherein each R7is selected from hydrogen, bromo, iodo, and -B(R21)2.

98. The process of any one of claims 27 to 97, wherein each R7is selected from hydrogen, iodo, and -B(R21)2.

99. The process of any one of claims 27 to 98, wherein each R5and R6are independently selected from -Si(R20)3 and Ci-6 alkyl; orone R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl.

100. The process of any one of claims 27 to 99, wherein each R5and R6are independently selected from -Si(R20)3, and Ci-6 alkyl; orone R5and one R6are taken together to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-4 alkyl.

101. The process of any one of claims 27 to 100, wherein each R20is independently selected from Ci-4 alkyl.

102. The process of any one of claims 27 to 101, wherein each R22is independently selected from hydrogen; ortwo R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle which is optionally substituted with one or more substituents independently selected from Ci-io alkyl.WSGR Docket No. 63230-734.601103. The process of any one of claims 27 to 102, whereintwo R22on different O atoms are taken together with the O atom to which each R22is attached to form a heterocycle, which is optionally substituted with one or more substituents independently selected from Ci-6 alkyl.

104. A compound prepared by the process of any one of claims 27 to 103, wherein the compound is selected from:WSGR Docket No. 63230-734.601pharmaceutically acceptable salt of any one thereof.

105. A compound represented by the structure of Formula (II) prepared by the process of anyWSGR Docket No. 63230-734.601one of claims 27 to 52 or 86 to 104, the compound is selected from:or a pharmaceutically acceptable salt of any one thereof.

106. A compound represented by the structure of Formula (III) or Formula (III*) prepared by the process of any one of claims 53 to 67 or 86 to 104, wherein the compound is selected from:WSGR Docket No. 63230-734.601107. A compound represented by the structure of Formula (IV) or Formula (IV*) prepared by the process of any one of claims 68 to 104, wherein the compound is selected from:or a pharmaceutically acceptable salt of any one thereof.

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